Med Notes

Medicine
Alasdair Scott
BSc (Hons) MBBS PhD
2012
dr.aj.scott@gmail.com
Table of Contents
1. Cardiology ........................................................................................................................................... 1
2. Pulmonology ..................................................................................................................................... 35
3. Endocrinology ................................................................................................................................... 59
4. Gastroenterology............................................................................................................................... 78
5. Nephrology ...................................................................................................................................... 103
6. Haematology ................................................................................................................................... 118
7. Infectious Disease ........................................................................................................................... 137
8. Neurology ........................................................................................................................................ 153
9. Rheumatology ................................................................................................................................. 198
10. Clinical Chemistry ......................................................................................................................... 211
11. Oncology ....................................................................................................................................... 222
12. Immunology ................................................................................................................................... 227
13. Dermatology .................................................................................................................................. 232
14. Epidemiology ................................................................................................................................. 240
15. Emergencies ................................................................................................................................. 246

Cardiology
Contents
Cardiac Electrophysiology ............................................................................................................................................................. 2
ECG Analysis ................................................................................................................................................................................ 3
ECG Abnormalities ........................................................................................................................................................................ 4
Bradycardias................................................................................................................................................................................ 10
Narrow Complex Tachycardias = SVT ........................................................................................................................................ 11
Atrial Fibrillation ........................................................................................................................................................................... 13
Acute Coronary Syndromes ........................................................................................................................................................ 14
MI Complications ......................................................................................................................................................................... 15
STEMI Management.................................................................................................................................................................... 16
Angina Pectoris ........................................................................................................................................................................... 18
Heart Failure: Concepts and Causes .......................................................................................................................................... 19
Chronic Heart Failure .................................................................................................................................................................. 20
Severe Pulmonary Oedema ........................................................................................................................................................ 21
Cardiogenic Shock ...................................................................................................................................................................... 22
Hypertension ............................................................................................................................................................................... 23
Aortic Stenosis............................................................................................................................................................................. 24
Aortic Regurgitation ..................................................................................................................................................................... 25
Mitral Stenosis ............................................................................................................................................................................. 26
Mitral Regurgitation ..................................................................................................................................................................... 27
Mitral Valve Prolapse (Barlow Syndrome) .................................................................................................................................. 27
Right Heart Valve Disease .......................................................................................................................................................... 28
Infective Endocarditis .................................................................................................................................................................. 29
Pericardial Disease...................................................................................................................................................................... 31
Myocardial Disease ..................................................................................................................................................................... 32
Congenital Heart Disease ........................................................................................................................................................... 33
Inherited Connective Tissue Disorders ....................................................................................................................................... 34
Alasdair Scott, 2012 1

Cardiac Electrophysiology
View Leads Vessel

Inferior II, III, aVF RCA
Anterolateral I, aVL, V5 + V6 L circumflex
Anteroseptal V2-V4 LAD
Anterior V2-V6 Left main stem
Posterior V1, V2, V3 (recip) RCA

ECG Analysis
1. Rate 6. PR interval (120-200ms)
300 / no. of large squares Start of P wave to start of QRS
6 = 50 Long: heart block
5 = 60 Short
4 = 75 Accessory conduction: e.g. WPW
3 = 100 Nodal rhythm
2 = 150 HOCM
1 = 300 Depressed: pericarditis
2. Rhythm 7. QTc (380-420ms)

Look for P waves followed by QRS complexes Start of QRS to end of T wave
AF Bazetts formula: QTc = actual QT/R-R
No discernable P waves Long (>420ms): TIMME
Irregularly irregular QRS Toxins
Atrial flutter: saw-toothed baseline Macrolides
Nodal rhythm: regular QRS but no P waves Anti-arhythmics (Ia/III): quinidine, amiod
TCAs
Histamine antagonists
3. Axis Inherited: e.g. Romano-Ward, Jervell (c SNHL)
I and II +ve = normal axis (-30 +90) Ischaemia
I +ve and II ve (leaving) = LAD (-30 -90) Myocarditis
I ve and II +ve (reaching) = RAD (+90 +180) Mitral valve prolapse
Electrolytes: Mg, K, Ca, temp
Short (<380ms)
RAD (> +90) LAD (<-30) Digoxin
Anterolateral MI Inferior MI -B
RVH, PE LVH Phenytoin
L post. hemiblock L ant. Hemiblock
WPW WPW
ASD secundum ASD primum 8. ST Segments
Elevated (limbs: >1mm, chest: >2mm)
Acute MI
4. P Waves Prinzmetals angina
Pericarditis: saddle-shaped
Absent: AF, SAN block, nodal rhythm
Aneurysm: ventricular
Dissociated: complete heart block
P mitrale: bifid P waves = LA hypertrophy
Depressed (>0.5mm)
HTN, AS, MR, MS
Ischaemia: flat
P pulmonale: peaked P waves= RA hypertrophy Digoxin: down-sloping
pulmonary HTN, COPD
5. QRS 9. T-waves
Wide QRS (>120ms) Normally inverted in aVR and V1
Ventricular initiation + V2-V3 in blacks
Conduction defect
Abnormal if inverted in: I, II and V4-6
WPW
Strain
Pathological Q wave Ischaemia
>1mm wide and > 2mm deep Ventricular hypertrophy
Full Thickness MI BBB
RVH: Dominant R wave in V1 + deep S wave in V6 Digoxin
LVH Peaked in K+
R wave in V6 >25mm Flattened in K+
R wave in V5/V6 + S wave in V1 > 35mm
10. Extras
U waves
Occur after T waves
Seen in K
J waves / Osborne wave
Occur between QRS and ST segment
Causes
hypothermia < 32OC
SAH
Hypercalcaemia
ECG Abnormalities
Conduction Defects
Abnormality Features ECG

1st Degree Heart Block PR > 200ms
2nd Degree Heart Block Progressive lengthening of

- Wenckebach /Mobitz I PR interval
One non-conducted P wave
Next conducted beat has

shorter PR interval
2nd Degree Heart Block Constant PR
- Mobitz II
Occasional non-conducted P
waves
Often wide QRS

- block is usually in bundle
branches of Purkinje fibres
2nd Degree Heart Block Two P waves per QRS
- 2:1 Block
Normal consistent PR
intervals
3rd Degree Heart Block P waves and QRS @

different rates
- dissociation
Abnormally shaped QRS

- ventricular origin (40bpm)
Abnormality Features ECG Aetiology

Right BBB MaRRoW Infarct Inferior MI
Wide QRS Normal variant
RSR pattern in V1 Congenital ASD, VSD, Fallots
Hypertrophy RVH (PE, Cor
Pulmonale)
Left BBB WiLLiaM Fibrosis

Wide QRS c notched LVH AS, HTN
top Infarct Inf. MI
T wave inversion in lat Coronary HD
leads
Bifascicular Block RBBB + LAD RBBB + Left ant. hemiblock

Trifascicular Block RBBB + LAFB + 1st
degree AV block

Escape Rhythms: appear late (after anticipated beat)
Atrial Escape SAN fails to depolarise
Abnormal P wave
Normal QRS
60-80bpm
Junctional Escape Usually no P waves
(occasionally after QRS)
Normal QRS
40-60bpm
Ventricular Escape Usually result of complete
AV block regular P
waves seen (top).
May be SAN failure no P

waves (below).
Wide QRS,
20bpm
Extrasystoles: appear early (before anticipated beat)

Atrial Extrasystole Abnormal P wave
Normal QRS
Nodal Extrasystole P wave buried in QRS or

sometimes immediately
before/after QRS.
- may be negative
Normal QRS
Ventricular No P wave.
Extrasystole
Wide QRS and abnormal T
wave.

Narrow Complex Tachycardias
AV Nodal Re- P wave absent or immediately
entrant before/after QRS
Tachycardia
Normal QRS
AVRT P waves usually visible

between QRS complexes
QRS may be narrow or wide
Accessory conduction bundle

Atrial Tachycardia Abnormally shaped P waves
Normal QRS complexes.
Rate > 150bpm
May be assoc.
c AV block.
Atrial Flutter Saw-toothed baseline as

atria contract @ 300bpm.
AVN cant conduct > 200bpm

AV block occurs.
- 2:1(150), 3:1(100), 4:1(75)
Normal QRS
Atrial Fibrillation No P waves irregular line
Irregularly irregular QRS

Broad Complex Tachycardias
VT No P waves
Regular, wide QRS
No T waves
Torsades
VF Shapeless, rapid
oscillations and no
organised complexes.
Ventricular tachycardia vs. SVT with bundle branch block
VT more likely if:

Hx: recent infarction
Atrioventricular dissociation
Broad QRS complexes (>140ms)
Concordant QRS direction in V1-V6
Fusion and capture beats

P Wave Abnormalities
P pulmonale Peaked P wave RAH
- pulmonary HTN
- tricuspid stenois
P mitrale Broad, bifid P wave LAH

- mitral stenois
QRS Abnormalities
RVH Tall R wave in V1 Cor pulmonale
Deep S wave in V6
RAD
Normal QRS width
May be T wave inversion in

V1-V3
LVH S in V1 + R in V6 >35mm HTN
and/or R wave in V6 >25mm AS
COA
May be LAD H(O)CM
May be T wave inversion in

II, aVL, V5, V6

Miscellaneous
WPW Accessory conducting bundle.
Short PR interval
Slurred upstroke of QRS called a

delta wave (V3/4).
Can establish re-entrant circuit

SVT (antidromic AVRT)
AF + WPW irregularly irregular

broad QRS complexes (below).
Brugada RBBB
Syndrome
Coved ST elevation in V1-V3
Digoxin Reverse tick

- Down-sloping ST depression
- T wave inversion
PE SI QIII TIII (rare)

- deep S wave in I (RAD)
- pathological Q in III
- T inversion in III
Right vent strain

- RAD (S wave in I)
- Dominant R wave and T
wave inversion in V1-V3
K+ Tall tented T waves
Widened QRS
Absent P waves
Sine wave appearance
Fig shows serial in K+
K+ Small T waves
ST depression
Prolonged QT interval
Prominent U waves

Bradycardias
(<60bpm)
Causes: DIVISIONS Classification

Sinus bradycardia
Drugs First degree heart block: PR > 200ms
Antiarrhythmics (type 1a, amiodarone) Second degree heart block
-blockers Wenkebach / Mobitz I
Ca2+-channel blockers (verapamil) Mobitz II
Digoxin Complete heart block
Junctional: narrow QRS @ ~50bpm
Ischaemia / Infarction Ventricular: broad QRS @ ~40bpm
Inferior MI
Rx
Vagal hypertonia If asymptomatic and rate >40: no Rx needed
Athletes
Vasovagal syncope
Carotid sinus syndrome Urgent / rate <40bpm
1. Rx underlying cause: e.g. drugs, MI
Infection
Viral myocarditis 2. Medical
Rheumatic fever Atropine 0.61.2g (max 3g) IV
Infective endocarditis Isoprenaline IVI
Sick sinus syndrome 3. Pacing: External

Structural damage or fibrosis of SAN, AVN or
conducting tissue
PC Elective
SVT alternating c either sinus bradycardia 1. Permanent pacing
arrest or SA/AV block Mobitz II
Rx Complete AV block
Bradyarrhythmias: pace Sick sinus
Tachyarrhythmias: amiodarone AF
Drug-resistant tachyarrhythmias
Infiltration: restrictive / dilated cardiomyopathy
Autoimmune
Sarcoid
Haemochromatosis
Amyloid
Muscular dystrophy
O
hypOthyroidism
hypOkalaemia (or )
hypOthermia
Neuro: ICP
Septal defect: primum ASD
Surgery or catheterisation

Narrow Complex Tachycardias = SVT
Definition: Rate >100bmp, QRS width < 120ms
Differential Principles of Mx
1. Sinus tachycardia If pt. compromised sedate + DC cardioversion
Otherwise ID rhythm and Rx accordingly
2. Atrial Key to ID irregular rhythm = AF = different Rx
AF Vagal manoeuvres (carotid sinus massage, valsalva) transiently AV block and
Atrial flutter may unmask underlying atrial rhythm.
Atrial tachycardia If manoeuvres unsuccessful, give adenosine while recording rhythm strip
transient AV block, unmasking atrial rhythm
3. AV nodal re-entry tachycardia cardioverts AVNRT/AVRT to sinus rhythm
If adenosine fails, choose from:
4. AV re-entry tachycardia Digoxin
Atenolol
Verapamil (not if on -blocker)
Amiodarone
If unsuccessful DC cardioversion
Mx
O2 + IV access
Regular rhythm? NO Treat as AF

Control rate
c -B (e.g. metoprolol) or digoxin
YES If onset <48h consider cardioversion c amiodarone (as
below) or DC shock
Continuous ECG trace Consider anticoagulation c heparin and/or warfarin
Vagal manoeuvres
Adenosine 6mg IV bolus NB. Avoid adenosine, CCB, -B in AF/Flutter with WPW or Hx
Then 12mg, then 12mg of WPW as may VF. Use Amiodarone or flecainide
YES
Adverse Signs? Sedation
BP <90
HF
consciousness
Synchronised cardioversion:
HR >200 100200360J
NO
Choose from:
Amiodarone:
Digoxin (500ug over 30min)
Amiodarone 300mg over 20-60min
Verapamil Then 900mg over next 23h
Atenolol
Adenosine Prophylaxis
MOA: temporary AVN block -B
SEs: Transient chest tightness, dyspnoea, flushing, headache AVRT: flecainide
Relative CIs: asthma, 2nd/3rd degree block AVNRT: verapamil
Interactions
fx d by dipyridimole
fx d by theophylline

Definition: Rate >100bmp, QRS width > 120ms VT Causes: IM QVICK
Infarction (esp.
c ventricular aneurysm)
Differential Myocarditis
1. VT QT interval
2. Torsades de points Valve abnormality: mitral prolapse, AS
3. SVT
c BBB Iatrogenic: digoxin, antiarrhythmics, catheter
Cardiomyopathy (esp. dilated)
K, Mg, O2, acidosis
Mx
Pulse? CPR
NO
YES
O2 + IV access
YES
BP <90
HF
Chest pain
consciousness
HR > 150 200300360
NO
Correct Electrolyte Problems Amiodarone:

K+: max 60mM KCL @ 20mmol/h 300mg over 20-60min
Mg2+: 4ml 50% MgSO4 in 30min Then 900mg over next 23h
Assess Rhythm
Regular (i.e. VT):
Amiodarone (see opposite)
Or lignocaine 50mg over 2min
If irregular, Dx is usually:
AF c BBB
Pre-excited AF: flec / amio Recurrent / Paroxysmal VT
TDP: MgSO4 2g IV over 10 min
Medical:
Amiodarone
Failure
-B
Synchronised Cardioversion
ICD

Atrial Fibrillation
Pathology Persistent AF
LA loses refractoriness before the end of atrial systole. >7d, may recur even after cardioversion
recurrent, uncoordinated contraction @ 300-600bpm
Atrial contraction responsible for ~25% of CO Try rhythm control first-line if:
often triggers heart failure Symptomatic or CCF
Younger (<65)
Causes Presenting first time
c lone AF
Secondary to treated precipitant
Common Other
IHD Alcohol Rhythm Control
Rheumatic heart disease Pneumonia TTE first: structural abnormalities
Thyrotoxicosis PE Anticoagulate c warfarin for 3wks
Hypertension Post-op or use TOE to exclude intracardiac thrombus.
Hypokalaemia Pre-Rx 4wks c sotalol or amiodarone if risk of failure
RA Electrical or pharmacological cardioversion
4 wks anticoagulation afterwards (target INR 2.5)
Symptoms
Asympto Maintenance antiarrhythmic
Chest pain Not needed if successfully treated precipitant
st
Palpitations 1 : -B (e.g. bisoprolol, metoprolol).
Dyspnoea 2nd: amiodarone
Faintness
Other options
Radiofrequency ablation of AV node
Signs Maze procedure
Irregularly irregular pulse
Pacing
Pulse deficit: difference between pulse and HS
Fast AF loss of diastolic filling no palpable
pulse Rate control (target <90bpm at rest):
Signs of LVF 1st line: -B or rate-limiting CCB (NOT both!)
2nd line: add digoxin (dont use as monotherapy)
3rd line: consider amiodarone
Ix
ECG Mx of Permanent AF
FBC, U+E, TFTs, Trop
Failed cardioversion / unlikely to succeed
Consider TTE: structural abnormalities AF >1yr, valve disease, poor LV function
Pt. doesnt want cardioversion
Rate control
Acute AF (48h)
Haemo unstable emergency cardioversion Mx of Atrial Flutter
(IV amiodarone 2nd line) Manage as for AF
Anti-AF drugs may not work, but try
Control ventricular rate Amiodarone to restore sinus
1st line: diltiazem or verapamil or metoprolol Amiodarone or sotalol to maintain it
2nd line: digoxin or amiodarone Cavotricuspid isthmus ablation (RA) is Rx of choice.
Start LMWH CHA2-DS2-VAS Score

Determines necessity of anticoagulation in AF
Cardioversion: only if acute AF <48hrs Warfarin CI in AF
Electrical cardioversion or pharmacological Bleeding diathesis, plats, BP > 160/90, poor
1st: Flecainide (if no structural heart disease) compliance
2nd: Amiodarone Dabigatran may be cost-effective alternative.
Long-term anticoagulation not needed if sinus restored
no RFs (0 CHADSVAS) + low recurrence risk. CHA2-DS2 VAS
CCF Vascular disease
HTN Age: 65-74yrs
Paroxysmal AF Age75 (2 points) Sex: female
Self-limiting, <7d, recurs DM
Anticoagulate: use CHADSVAS Stroke or TIA (2 points)
Rx pill-in-pocket : flecainide, propafenone
Prevention: -B, sotalol or amiodarone Score
0: aspirin 300mg
1: Warfarin

Acute Coronary Syndromes
Definition Investigations
ACS = unstable angina + evolving MI
Divided into: ECG
ST elevation or new onset LBBB STEMI Sequence
NSTEMI Normal
ST elevation + hyperacute (tall) T waves
Q waves: full-thickness infarct
Epidemiology Normalisation of ST segments
T wave inversion
Incidence 5/1000 for STEMI
(New onset LBBB also = STEMI)
NSTEMI
ST depression
Pathophysiology T wave inversion
Plaque rupture, thrombosis and inflammation. No Q waves = subendocardial infarct
Rarely due to coronary spasm
View Leads Vessel Complication
Inferior II, III, aVF RCA Bradyarrhythmias
Risk Factors Anterolateral I, aVL, V4-V6 LCx
Anteroseptal V2-V4 LAD
Modifiable Non-modifiable Anterior V2-V6 LMS LVF
HTN Age Posterior V1, V2, V3 (recip) RCA
DM Male
Smoking FH (MI < 55yrs) Bloods
cholesterol Troponin T/I
Obesity Myofibrillar proteins linking actin and myosin
Elevated from 3-12h
Symptoms need 12h trop to exclude MI
Peak 24h
Acute central/left chest pain >20min
Baseline from 5-14d
Radiates to left jaw or arm
FBC, U+E, glucose, lipids, clotting
Nausea
Sweating
CXR
Dyspnoea
Cardiomegaly
Palpitations
Pulmonary oedema
Widened mediastinum: aortic rupture
May get silent MIs in elderly/diabetics
Syncope
Delirium
Post-op oliguria / hypotension Diagnosis
STEMI / LBBB: Typical symptoms + ST elevation (/LBBB)
NSTEMI: Typical symptoms + no ST elevation + +ve trop
UA: Typical symptoms + no ST elevation + -ve trop
Signs
Anxiety
Pallor Sweating
Pulse / Treatment
BP / STEMI: PCI or thrombolysis
4th heart sound NSTEMI / UA: medical + elective angio PCI/CABG
Signs of LVF (basal creps, JVP, 3rd HS)
PSM: papillary muscle dysfunction / rupture
Prognosis
Varies
c pt. factors
Differential STEMI: 30 day mortality ~15%
Angina NSTEMI: overall mortality 1-2%
Peri / endo / myocarditis
Dissection
PE, pneumothorax, pneumonia
Costochondritis
GI: e.g. GORD, spasm
Anxiety

MI Complications
Death Passing PRAED st.
Aneurysm: ventricular
Death: VF, LVF, CVA
Presentation
4-6wk
Pump Failure LVF
Angina
Pericarditis Recurrent VT
Presentation Systemic emboli.
Occurs early
Mild fever ECG: persistent ST elevation.
Central chest pain / change in pain
Relieved by sitting forward Rx
Pericardial friction rub Anticoagulate
Consider Excision
ECG
Saddle-shaped ST elevation
PR depression Embolism
Arise from LV mural thrombus
Rx Consider warfarin for 3mo after large anterior MI
NSAIDs: ibuprofen
Echo to exclude effusion
Dresslers Syndrome: pleuro-pericarditis
Due to auto-antibodies vs. myocyte sarcolemma.
Rupture: myomalacia cordis
Cardiac tamponade: Left ventricular free wall rupture Presentation
Becks triad (BP, JVP, muffled heart sounds) 2-6wks
Pulsus paradoxus Recurrent pericarditis
Papillary muscle / chordae MR Pleural effusions
PSM Fever
Pulmonary oedema. Anaemia
Septum ESR
PSM
JVP Rx
Heart failure NSAIDs
Steroids if severe
Arrhythmias
Tachycardias
SVT
Sinus tachycardia give O2 + analgesia
AF or flutter
Compromised DC cardioversion
Otherwise rate control: digoxin -B
Ventricular
Frequent PVC common after acute MI: no Rx
Sustained VT
Compromised DC cardioversion
Else amiodarone or lignocaine
May need pacing
VF
Early (<48hrs): reperfusion (good prog)
Late (>48hrs): extensive heart damage
Rx: DC shock
Bradycardias
Sinus bradycardia
esp. in inferior MI.
Rx: atropine 0.6 1.2mg
AV block
Pace Mobitz II
Ventricular bradycardia
Suggests SA and AV node damage
STEMI Management
12 lead ECG Primary Percutaneous Coronary Intervention

Rx of choice if <12h
Angioplasty and stenting
+ GP IIb/IIIa antagonist (tirofiban) if high risk
O2 2-4L aim for SpO2 94-98% Delayed PCI, DM, complex procedure
Complications:
Bleeding
IV access Emboli
Bloods for FBC, U+E, glucose, lipids Arrhythmia
Thrombolysis
Brief assessment CI beyond 24hrs from pain onset
Hx of CVD and risk factors
Thrombolysis CIs ECG Criteria:
CV exam ST elevation > 1mm in 2+ limbs or > 2mm in 2+ chest leads.
New LBBB
Posterior: Deep ST depression and tall R waves in V1-V3
Antiplatelet Contraindications: AGAINST

Aspirin 300mg PO (then 75mg/d) Aortic dissection
Clopidogrel 300mg PO (then 75mg/d) GI bleeding
Allergic reaction previously
Iatrogenic: recent surgery
Neuro: cerebral neoplasm or CVA Hx
Analgesia Severe HTN (200/120)
Morphine 5-10mg IV Trauma, inc. CPR
Metoclopramide 10mg IV st
Agents: 1 : streptokinase, alteplase (rt-PA), tenecteplase
Complications:
Anti-ischaemia Bleeding
GTN 2 puffs or 1 tablet SL Stroke
-B atenolol 5mg IV (CI: asthma, LVF) Arrhythmia
Allergic reaction
Pts. not receiving any form of reperfusion therapy should be given

LMWH: e.g. enoxaparin IV then SC
fondaparinux.
Continuing Therapy: address risk factors

Admit to CCU for monitoring ACEi: start w/i 24hrs of MI (e.g. lisinopril 2.5mg)
Arrhythmias -blocker: e.g. bisoprolol 10mg OD (or, CCB)
Continue meds except CCBs Cardiac rehabilitation (group exercise and info) / Heart Manual
DVT prophylaxis until fully mobile
Continue for 3mo if large anterior MI
Statin: regardless of basal lipids (e.g. atorvastatin 80mg)
Primary PCI or Thrombolysis
Advice
Stop smoking
Diet: oily fish, fruit, veg, sat fats
Exercise: 30min OD
Work: return in 2mo
Sex: avoid for 1mo
Driving :avoid for 1mo
NB. Continue clopidogrel for 1mo following STEMI

Continue aspirin indefinitely.

NSTEMI and UA Management
12 lead ECG + Admit to CCU
O2 2-4L aim for SpO2 94-98%
IV access
Bloods for FBC, U+E, glucose, lipids,
Troponin
Brief Assessment
CV exam
Antiplatelet
Aspirin 300mg PO (then 75mg/d)
Clopidogrel 300mg PO
Anticoagulate
Fondaparinux 2.5mg SC
Analgesia
Morphine 5-10mg IV
Metoclopramide 10mg IV
Anti-ischaemia
GTN: 2 puffs or 1 tablet SL
-B: atenolol 50mg/24h PO (CI: asthma, LVF)
IV GTN if pain continues
Assess Cardiovascular Risk: GRACE/TIMI
Intermediate- to High-Risk Low-Risk

Persistent/recurrent ischaemia, ST depression, DM, No further pain, flat or inverted T waves or normal
positive trop. ECG, negative trop.
GPIIb/IIIa antagonist (tirofiban) May discharge if 12h trop is negative.
Angiography (PCI) w/i 96hrs Outpatient tests: angio, perfusion scan, stress echo
Clopidogrel 75mg/d for one year

ACEi (e.g. lisinopril 2.5mg)
-blocker (e.g. bisoprolol 10mg OD) or (CCB)
Cardiac rehabilitation (group exercise and info) / Heart Manual
Stop antithrombotic therapy when pain free (but give 3-5d)
Statin (e.g. atorvastatin 80mg)
General advice as above

NB. Continue clopidogrel for 1yr following NSTEMI
Angina Pectoris
Pathophysiology Mx
Atherosclerosis myocardial ischaemia
Lifestyle
Aetiology Stop smoking
Mostly atheroma. Wt. loss and exercise
Anaemia Healthy diet: oily fish, fruit, veg, sat fats
AS
Tachyarrhythmias Medical
Arteritis 2O Prevention: prevent cardiovascular events
Aspirin 75mg OD
ACEi (esp. if angina + DM)
Risk Factors Statins: simvastatin 40mg
Modifiable: Non-modifiable: Antihypertensives
HTN Age
DM Male Anti-anginals: prevents angina episodes
Smoking FH (MI < 55yrs) 1. GTN (spray or SL) + either
cholesterol Genetic: e.g. hyperlipidaemia 1st: -B (e.g. Atenolol 50-100mg OD)
Obesity 2nd: CCB (e.g. Verapamil 80mg TDS)
2. If either -B or CCB doesnt control symptoms,
Symptoms try the other option.
Central chest tightness or heaviness 3. Can try -B + dihydropyridine CCB
e.g. amlodipine MR 10mg/24h
Brought on by exertion, relieved by rest
4. If symptoms still not controlled
May radiate to one/both arms, neck, jaw or teeth
ISMN 20-40mg BD (8h washout @ PM) or
Other ppts: emotion, cold weather, heavy meals slow-release nitrate (Imdur 60mg OD)
Ivabradine (esp. if cant take -B)
Classification Nicorandil 10-30mg BD
Stable: induced by effort Ranolazine
Unstable: occurs at rest / minimal exertion
Decubitus: induced by lying down
Prinzmetals / variant: occurs during rest Interventional: PCI
Due to coronary spasm Indications
ST elevation during attack: resolves as pain Poor response to medical Rx
subsides. Refractory angina but not suitable for CABG
Rx: CCB + long-acting nitrate Complications
Syndrome X: angina pain + ST elevation on exercise Re-stenosis (20-30% @ 6mo)
test but no evidence of coronary atherosclerosis. Emergency CABG (<2%)
Probably represents small vessel disease MI (<2%)
Death (<0.5%)
Differential Clopidogrel s risk of re-stenosis
Bare metal stent: 1mo
AS
Drug-eluting (e.g. sirolimus) stent: 1yr
Aortic aneurysm
GI: GORD, spasm
Musculoskeletal Surgical: CAGB
Indications
Ix L main stem disease
Bloods: FBC, U+E, lipids, glucose, ESR, TFTs Triple vessel disease
ECG: usually normal Refractory angina
May show ST , flat/inverted T waves, past MI Unsuccessful angioplasty
Consider exercise ECG Complications
Stress echo MI
Perfusion scan Stroke
CT coronary Ca2+ score Pericardial tamponade or haemothorax
Angiography (gold standard) Postperfusion syn.
Post-op AF
Nonunion of sternum
Graft stenosis

Heart Failure: Concepts and Causes
Definition: CO is inadequate for the bodys requirements despite adequate filling pressures.
Epidemiology RVF
Prev: 2% @ 50yrs 10% @ 80yrs
Causes
LVF
Pathophysiology Cor pulmonale
Tricuspid and pulmonary valve disease
Reduced CO initially compensation
Starling effect dilates heart to enhance contractility Symptoms
Remodelling hypertrophy Anorexia and nausea
RAS and ANP/BNP release
Sympathetic activation Signs
JVP + jugular venous distension
Progressive in CO decompensation Tender smooth hepatomegaly (may be pulsatile)
Progressive dilatation impaired contractility + Pitting oedema
functional valve regurgitation Ascites
Hypertrophy relative myocardial ischaemia
+
RAS activation Na and fluid retention venous
pressure oedema LVF
Sympathetic excess afterload CO
Causes
1st: IHD
Low Output: CO and fails to c exertion 2nd: idiopathic dilated cardiomyopathy
3rd: Systemic HTN
1. Pump failure 4th: Mitral and aortic valve disease
Systolic failure impaired contraction Specific cardiomyopathies
Ischaemia/MI (commonest cause)
Dilated cardiomyopathy Symptoms
Hypertension Fatigue
Myocarditis Exertional dyspnoea
Orthopnoea + PND
Diastolic failure impaired filling Nocturnal cough ( pink, frothy sputum)
Pericardial effusion / tamponade / constriction Wt. loss and muscle wasting
Cardiomyopathy: restrictive, hypertrophic
Signs
Arrhythmias Cold peripheries cyanosis
Bradycardia, heart block Often in AF
Tachycardias Cardiomegaly c displaced apex
Anti-arrhythmics (e.g. beta-blocker, verapamil) S3 + tachycardia = gallop rhythm
Wheeze (cardiac asthma)
2. Excessive pre-load Bibasal creps
AR, MR
Fluid overload
3. Excessive afterload Acute vs. Chronic

AS Acute
HTN New onset or decompensation of chronic
HOCM Peripheral / pulmonary oedema
evidence of peripheral hypoperfusion
Chronic
Develops / progresses slowly
High Output: needs RVF initially, then LVF Venous congestion common
Anaemia, AVM Arterial pressure maintained until v. late
Thyrotoxicosis, Thiamine deficiency (beri beri)
Pregnancy, Pagets

Chronic Heart Failure
Dx of CCF: Framingham Criteria General Mx
2 major criteria or 1 major + 2 minor
1O/2O Cardiovascular Risk
Major Minor Stop smoking
PND Bilat ankle oedema salt intake
+ve abdominojugular reflux SOBOE Optimise wt.: or - dietician
Neck vein distension HR >120 Supervised group exercised based rehab programme
S3 Nocturnal cough Aspirin
Basal creps Hepatomegaly Statins
Cardiomegaly Pleural effusion
Acute pulmonary oedema 30% vital capacity Rx Precipitants / Causes
CVP (>16cmH2O) Underlying cause
Wt. loss >4.5kg in 5d 2O to Rx Valve disease
Arrhythmias
Ischaemia
Ix Exacerbating factors
Bloods: FBC, U+E, BNP, TFTs, glucose, lipids Anaemia
CXR: ABCDE Infection
Alveolar shadowing BP
Kerley B lines
Cardiomegaly (cardiothoracic ratio >50%) Specific Mx
Upper lobe Diversion ACEi, -B and spiro mortality
Effusions
Fluid in the fissures 1st line: ACEi/ARB + -B + loop diuretic
ECG ACEi/ARB: e.g. lisinorpil or candesartan
Ischaemia Hydralazine + ISDN if not tolerated
Hypertrophy
AF -B: e.g. carvedilol or bisoprolol (licensed)
Echo: the key investigation Start low, go slow
Global systolic and diastolic function E.g. carvedilol 3.125mg/12h 25-50mg/24h
Ejection fraction normally ~60% Wait 2wks between increments
Focal / global hypokinesia Switch stable pts taking a -B for a comorbidity
Hypertrophy to a -B licensed for heart failure
Valve lesions -B therapy may be particularly good in COPD
Intracardiac shunts
Loop diuretic: frusemide or bumetanide
B-type Natriuretic Peptide: BNP or NTproBNP nd
Secreted from ventricles in response to 2 line: get specialist advice
pressure stretch Spironolactone / eplerenone
Tachycardia Watch K carefully (on ACEi too)
Glucocorticoids
Thyroid hormones ACEi + ARB
Actions
GFR and renal Na reabsorption Vasodilators: hydralazine + ISDN
preload by relaxing smooth muscle Additional Rx in Blacks
BNP is a biomarker of heart failure rd
BNP (>100) better than any other variable and 3 line
clinical judgement in diagnosing heart failure Digoxin
BNP correlates c LV dysfunction Cardiac resynchronisation therapy ICD
i.e. most in decompensated heart failure
BNP = mortality Other Considerations
BNP <100 excludes heart failure (96% NPV) Monitoring
BNP also in RHF: cor pulmonale, PE BP: may be v. low
Renal function
Plasma K
New York Heart Association Classification Daily wt.
1. No limitation of activity Use amlodipine for comorbid HTN or angina
2. Comfortable @ rest, dyspnoea on ordinary activity Avoid verapamil, diltiazem and nifedipine (short-
3. Marked limitation of ordinary activity acting)
4. Dyspnoea @ rest, all activity discomfort
Invasive Therapies
Cardiac resynchronisation ICD
Intra-aortic balloon counterpulsation
LVAD
Heart transplant (70% 5ys)
Severe Pulmonary Oedema
Sit pt. up Causes
Cardiogenic
MI
O2
Arrhythmia
15L/min via reservoir mask
Fluid overload: renal, iatrogenic
Target SpO2: 94-98%
Non-cardiogenic
ARDS: sepsis, post-op, trauma
IV access + monitor ECG Upper airway obstruction
Bloods for FBC, U+E, troponin, BNP, ABG Neurogenic: head injury
Rx any arrhythmias (e.g. AF)
Symptoms
Dyspnoea
Diamorphine 2.5-5mg IV Orthopnoea
+ Metoclopramide 10mg IV Pink frothy sputum
Frusemide 40-80mg IV Signs

Distressed, sweaty, cyanosed
HR, RR
JVP
GTN 2 puffs or 2 x 300ug tabs SL
S3 / gallop rhythm
Unless SBP <90mmHg
Bibasal creps
Pleural effusions
Hx, Ex, Ix
CXR: ABCDE
ECG: MI, arrhythmias, pulsus alternans Differential
Consider echo Asthma/COPD
Pneumonia
PE
If SBP >100mmHg, start nitrate IVI
ISMN 2-10mg/h IVI
Keep SBP >90 Monitoring Progress
BP
HR and RR
If worsening, consider: JVP
CPAP Urine Output
More frusemide or nitrate infusion ABG
Haemofiltration / dialysis
If SBP <100mmHg: Rx as cardiogenic shock

i.e. consider inotropes
Continuing Therapy
Daily weights
DVT prophylaxis
Repeat CXR
Change to oral frusemide or bumetanide
ACEi + -B if heart failure
Consider spironolactone
Consider digoxin warfarin (esp. if in AF)
Morphine in Pulmonary Oedema

Make pt. more comfortable
Pulm venodilators pre-load optimise position on Starling Curve
Cardiogenic Shock
O2 Definition
15L/min via reservoir mask Inadequate tissue perfusion primarily due to
Target SpO2: 94-98% cardiac dysfunction.
Causes: MI HEART
IV access + monitor ECG MI
Bloods for FBC, U+E, troponin, ABG Hyperkalaemia (inc. electrolytes)
Endocarditis (valve destruction)
Aortic Dissection
Diamorphine 2.5-5mg IV (pain/anxiety) Rhythm disturbance
+ metoclopramide 10mg IV Tamponade
Obstructive
Tension pneumo
Correct any:
Massive PE
Arrhythmias
Electrolyte disturbance
Acid-base abnormalities Presentation
Unwell: pale, sweaty, cyanosed, distressed
Cold clammy peripheries
Hx, Ex, Ix RR HR
CXR Pulmonary oedema
Echo
Consider CT thorax (dissection/PE)
Monitoring
CVP, BP, ABG, ECG, urine output.
Consider need for dobutamine
Rx underlying cause
Tamponade
Causes: Signs: Ix:

Trauma Becks triad: BP, JVP, muffled heart sounds Echo: diagnostic
Lung/breast Ca Kussmauls sign: JVP on inspiration CXR: globular heart
Pericarditis Pulsus paradoxus (pulse fades on inspiration)
MI
Bacteria (e.g. TB)
Mx:
ABCs
Pericardiocentesis (preferably under echo guidance)

Hypertension
Definitions Management
Stage 1: Clinic BP > 140/90 Do ABPM to confirm Dx before Rx (unless severe HTN)
Stage 2: Clinic BP > 160/100
Severe: Clinic BP > 180/110 Lifestyle interventions
Malignant: BP > 180/110 + papilloedema and/or retinal exercise
haemorrhage smoking, EtOH, salt, caffeine
Isolated SHT: SBP 140, DBP <90
Indications for Pharmacological Rx
Aetiology: PREDICTION <80yrs, stage 1 HTN (>140/90) and one of:
Primary: 95% Target organ damage (e.g. LVH, retinopathy)
Renal: RAS, GN, APKD, PAN 10yr CV risk 20%
Endo: T4, Cushings, phaeo, acromegaly, Conns Established CVD
Drugs: cocaine, NSAIDs, OCP DM
ICP Renal disease
CoA Anyone with stage 2 HTN (>160/100)
Toxaemia of Pregnancy (PET) Severe / malignant HTN (specialist referral)
Increased viscosity Consider specialist opinion if <40yrs with stage 1 HTN
Overload with fluid and no end organ damage.
Neurogenic: diffuse axonal injury, spinal section
BP Targets
Under 80yrs: <140/90 (<130/80 in DM)
Aetiological clues Over 80yrs: <150/90
HR: Thyrotoxicosis
RF-delay: CoA CV Risk Mx
Renal bruits: RAS O
Statins indicated for 1 prevention if 10yr CVD risk 20%
Palpable kidneys: APKD Aspirin may be indicated: evaluate risk of bleeding
Paroxysmal headache, tachycardia, sweating,
palpitations, labile or postural hypotension: phaeo
Antihypertensive Rx
End-organ damage: CANER < 55 > 55 / Black
Cardiac
IHD 1: A C (or D)
LVH CCF
AR, MR
Aortic 2: A + C (/D)
Aneurysm
Dissection
3: A+C+D
Neuro
CVA: ischaemic, haemorrhagic
Encephalopathy (malignant HTN)
4: Resistant HTN
A+C+D+ consider further diuretic (e.g.
Eyes: hypertensive retinopathy
spiro) or -blocker or -B.
Keith-Wagener Classification:
1. Tortuosity and silver wiring Seek expert opinion
2. AV nipping
3. Flame haemorrhages and cotton wool spots A: ACEi or ARB
4. Papilloedema e.g. lisinopril 10mg OD ( to 30-40mg)
Grades 3 and 4 = malignant hypertension e.g. candesartan 8mg OD (max 32mg OD)
C: CCB: e.g. nifedipine MR30-60mg OD
Renal D: Thiazide-like diuretic: e.g. chlortalidone 25-50mg OD
Proteinuria
CRF In step 2, use ARB over ACEi in blacks.
Avoid thiazides + -B if possible ( risk of DM).
Ix Only consider -B if young and ACEi/ARB not tolerated.
24h ABPM
Urine: haematuria, Alb:Cr ratio
Bloods: FBC, U+Es, eGFR, glucose, fasting lipids Malignant HTN
12 lead ECG: LVH, old infarct Controlled in BP over days to avoid stroke
Calculate 10yr CV risk Atenolol or long-acting CCB PO
Encephalopathy/CCF: fruse + nitroprusside / labetalol IV
Aim to BP to 110 diastolic over ~4h
Nitroprusside requires intra-arterial BP monitoring
Aortic Stenosis
Causes Ix
Senile calcification (60yrs +): commonest
Congenital: Bicuspid valve (40-60yrs), Williams syn. Bloods: FBC, U+E, lipids, glucose
Rheumatic fever
ECG
LVH
Symptoms LV strain: tall R, ST depression, T inversion in V4-V6
Triad: angina, dyspnoea, syncope (esp.
c exercise) LBBB or complete AV block (septal calcification)
LVF: PND, orthopnoea, frothy sputum May need pacing
Arrhythmias
CXR
Systemic emboli if endocarditis
Calcified AV (esp. on lateral films)
Sudden death
LVH
Evidence of failure
Post-stenotic aortic dilatation
Signs
Slow rising pulse
c narrow PP Echo + Doppler: diagnostic
Aortic thrill Thickened, calcified, immobile valve cusps
Apex: Forceful, non-displaced (pressure overload) Severe AS (AHA / ACC 2006 guidelines):
Heart Sounds Pressure gradient >40mmHg
Quiet A2 Jet velocity >4m/s (or by 0.3m/s in a yr)
Early syst. ejection click if pliable (young) valve Valve area <1cm
2
S4 (forceful A contraction vs. hypertrophied V)

Murmur Cardiac Catheterisation + Angiography
ESM Can assess valve gradient and LV function
Right 2nd ICS Assess coronaries in all pts. planned for surgery
Sitting forward in end-expiration
Radiates to carotids Exercise Stress Test
Contraindicated if symptomatic AS
May be useful to assess ex capacity in asympto pts.
Clinical Indicators of Severe AS
Quiet / absent A2 Mx
S4
Narrow pulse pressure Medical
Decompensation: LVF Optimise RFs: statins, anti-hypertensives, DM
Monitor: regular f/up
c echo
Angina: -B
Differential Heart failure: ACEi and diuretics
Coronary artery disease Avoid nitrates
MR
Aortic sclerosis Surgical
Valve thickening: no pressure gradient Poor prog. if symptomatic
Turbulence murmur Angina/syncope: 2-3yrs
ESM c no radiation and normal pulse LVF: 1-2yrs
HOCM Indications for valve replacement
ESM murmur which in intensity c valsalva (AS) Severe symptomatic AS
Severe asymptomatic AS c EF (<50%)
Severe AS undergoing CABG or other valve op
Aortic Stenosis Aortic Sclerosis Valve types
Valve narrowing due to fusion of Valve thickening Mechanical valves last longer but need
the commissures anticoagulation: young pts.
Narrow PP, slow rising pulse Bioprosthetic dont require anticoagulation but
Forceful apex fail sooner (10-15yrs)
ESM radiating carotids ESM
c no radiation
ECG: LVF Options for unfit patients
Balloon Valvuloplasty
Limited use in adults as complication rate is
high (>10%) and restenosis occurs in 6-12mo
Transcatheter Aortic Valve Implantation (TAVI)
Folded valve deployed in aortic root.
perioperative stroke risk cf. replacement
major bleeding
Similar survival @ 1yr
Little Long-term data

Aortic Regurgitation
Causes Ix
Acute Bloods: FBC, U+E, lipids, glucose

Infective endocarditis
Type A aortic dissection ECG: LVH (R6+S1 > 35mm)
Chronic CXR
Congenital: bicuspid aortic valve Cardiomegaly
Rheumatic heart disease Dilated ascending aorta
Connective tissue: Marfans, Ehlers Danlos Pulmonary oedema
Autoimmune: Ank spond, RA
Echo
Aortic valve structure and morphology (e.g. bicuspid)
Symptoms Evidence of infective endocarditis (e.g. vegetations)
LVF: Exertional dyspnoea, PND, orthopnoea
Severity
Arrhythmias (esp. AF) palpitations Jet width (>65% of outflow tract = severe)
Forceful heart beats Regurgitant jet volume
Angina Premature closing of the mitral valve
LV function: ejection fraction, end-systolic dimension
Signs
Collapsing pulse (Corrigans pulse) Cardiac Catheterisation
Wide PP Coronary artery disease
Apex: displaced (volume overload) Assess severity, LV function, root size
Heart Sounds
Soft / absent S2
S3 Mx
Murmur
EDM Medical
URSE + 3rd left IC parasternal
Optimise RFs: statins, anti-hypertensives, DM
Sitting forward in end-expiration
Monitor: regular f/up
c echo
ejection systolic flow murmur
Austin-Flint murmur systolic hypertension: ACEi, CCB
Underlying cause afterload regurgitation
High-arched palate
Spondyloarthropathy Surgery: aortic valve replacement
Embolic phenomena Definitive therapy
Indicated in severe AR if:
Symptoms of heart failure
Eponyms
Asympto c LV dysfunction: EF/ES dimension
Corrigans sign: carotid pulsation
De Mussets: head nodding
Quinckes: capillary pulsation in nail beds
Traubes: pistol-shot sound over femorals
Austin-Flint murmur
Rumbling MDM @ apex due to regurgitant jet
fluttering the ant. mitral valve cusp.
= severe AR
Duroziezs
Systolic murmur over the femoral artery c proximal
compression.
Diastolic murmur c distal compression
Clinical Indicators of Severe AR

Wide PP and collapsing pulse
S3
Long murmur
Austin Flint murmur
Decompensation: LVF

Mitral Stenosis
Causes Ix
Rheumatic fever
Prosthetic valve Bloods: FBC, U+E, LFTs, glucose, lipids
Congenital (rare)
ECG
AF
P mitrale (if in sinus)
Pathophysiology RVH c strain: ST depression and T wave inversion in V1-V2
Valve narrowing left atrial pressure loud S1
and atrial hypertrophy AF CXR
pulmonary oedema and PHT loud P2, PR LA enlargement
RVH left parasternal heave Pulmonary oedema: ABCDE
TR large v waves Mitral valve calcification
RHF JVP, oedema, ascites
Echo + Doppler
Severe MS (AHA 2006 Criteria)
Symptoms Valve orifice <1cm
2
Dyspnoea Pressure gradient >10mmHg

Fatigue Pulmonary artery systolic pressure >50mmHg
Chest pain Use TOE to look for left atrial thrombus if intervention
AF palpitations + emboli considered.
Haemoptysis: rupture of bronchial veins
Cardiac Catheterisation
Assess coronary arteries
Signs
Symptoms manifest when orifice <2cm2 (norm 4-6)
AF, low volume pulse Mx
Malar flush (CO backpressure + vasoconstriction)
JVP may be raised late on Medical
Prominent a waves: PTH Optimise RFs: statins, anti-hypertensives, DM
Large v waves: TR Monitor: regular f/up c echo
Absent a waves: AF Consider prophylaxis vs. rheumatic fever: e.g. Pen V
Left parasternal heave (RVH 2O to PHT) AF: rate control and anticoagulate
Apex: Tapping (palpable S1), non-displaced Diuretics provide symptom relief
Heart sounds
Loud S1 Surgical
Loud P2 (if PHT) Indicated in modsevere MS (asympto and symptomatic)
Early diastolic opening snap Percutaneous balloon valvuloplasty
Murmur Rx of choice
Rumbling MDM Suitability depends on valve characteristics
Apex Pliable, minimally calcified
Left lateral position in end expiration CI if left atrial mural thrombus
Radiates to the axilla Surgical valvotomy / commissurotomy: valve repair
O
Graham Steell murmur (EDM 2 to PR) Valve replacement if repair not possible
Clinical Indicators of Severe MS

Mitral facies
Longer murmur
Opening snap closer to 2nd heart sound
High LA pressure forcing valve open early
Decompensation: RVF
Complications
Pulmonary HTN
Emboli: TIA, CVA, PVD, ischaemic colitis
Hoarseness: rec laryngeal N. palsy = Ortners Syn
Dysphagia (oesophageal compression)
Bronchial obstruction

Mitral Regurgitation
Causes Ix
Mitral valve prolapse
Bloods: FBC, U+E, glucose, lipids
LV dilatation: AR, AS, HTN
Annular calcification contraction (elderly) ECG
Post-MI: papillary muscle dysfunction/rupture AF
Rheumatic fever P mitrale (unless in AF)
Connective tissue: Marfans, Ehlers-Danlos LVH
Symptoms CXR
Dyspnoea, fatigue LA and LV hypertrophy
AF palpitations + emboli Mitral valve calcification
Pulmonary congestion HTN + oedema Pulmonary oedema
Signs Echo
AF Doppler echo to assess MR severity: multiple criteria
Left parasternal heave (RVH) Jet width (vena contracta) >0.6cm
Apex: displaced Systolic pulmonary flow reversal
Volume overload as ventricle has to pump Regurgitant volume >60ml
forward SV and regurgitant volume TOE to assess severity and suitability of repair cf.
eccentric hypertrophy replacement.
Heart Sounds
Soft S1 Cardiac Catheterisation
S2 not heard separately from murmur Confirm Dx
Loud P2 (if PTH) Assess CAD
Murmur
Blowing PSM Mx
Apex Medical
Left lateral position in end expiration Optimise RFs: statins, anti-hypertensives, DM
Radiates to the axilla Monitor: regular f/up
c echo
AF: rate control and anticoagulate
Clinical Indicators of Severe MR Also anticoagulate if: Hx of embolism, prosthetic
Larger LV valve, additional MS
Decompensation: LVF Drugs to afterload can help symptoms
AF ACEi or -B (esp. carvedilol)
Diuretics
Differential
AS Surgical
TR Valve replacement or repair
VSD Indications
Severe symptomatic MR
Severe asympto MR c diastolic dysfunction: EF
Mitral Valve Prolapse (Barlow Syndrome)

Commonest valve prob. (~5%)
Causes Complications
Primary: myxomatous degeneration MR
Often young women Cerebral emboli
MI Arrhythmias sudden death
Marfans, ED
Turners Mx
-B may relieve palpitations and chest pain
Symptoms Surgery if severe (commonest reason for MV surgery)
Usually asymptomatic
Autonomic dysfunction: Atypical chest pain,
palpitations, anxiety, panic attack
MR: SOB, fatigue
Signs
Mid-systolic click late-systolic murmur

Right Heart Valve Disease
Tricuspid Regurgitation Pulmonary Regurgitation
Causes Causes
Functional: RV dilatation Any cause of pulmonary HTN
Rheumatic fever PR 2O to MS = Graham-Steell murmur
Carcinoid syndrome Signs
Murmur: Decrescendo EDM @ ULSE
Symptoms
Fatigue
Hepatic pain on exertion
Ascites, oedema Pulmonary Stenosis
Causes
Signs Usually congenital: e.g. Turners, Fallots
JVP
c giant V waves Rheumatic fever
RV heave Carcinoid syndrome
Murmur:
PSM Symptoms
LLSE in inspiration (Carvallos sign) Dyspnoea, fatigue
Pulsatile hepatomegaly Ascites
Jaundice Oedema
Ix Signs
LFTs Dysmorphia
Echo Large A wave
RV heave
Mx Ejection click, soft P2
Rx cause Murmur
Medical: diuretics, ACEi, digoxin ESM
Surgical: valve replacement ULSE L shoulder
Ix
Tricuspid Stenosis ECG
P pulmonale
Causes RAD
Rheumatic fever (with MV and AV disease) RBBB
CXR:
Symptoms Prominent pulmonary arteries: post-stenotic
Fatigue dilatation
Ascites Catheterisation: diagnostic
Oedema Mx: valvuloplasty or valvotomy
Signs
Large A waves
Opening snap
Murmur:
EDM
LLSE in inspiration
Mx
Medical: diuretics
Surgical: repair, replacement

Infective Endocarditis
Definition Ix
Cardiac valves develop vegetations composed of bacteria
and platelet-fibrin thrombus. Bloods
N.chromic, N.cytic anaemia
Risk Factors ESR, CRP
Cardiac disease Subacute Normal valves Acute +ve IgG RF (immune phenomenon)
Prosthetic valves Dental caries Cultures x 3, >12h apart
Degen. valvulopathy Post-op wounds Serology for unusual organisms
VSD, PDA, CoA IVDU (tricuspid valve)
Rheumatic fever Immunocomp. (inc. DM) Urine: Micro haematuria
Aetiology ECG: AV block

Culture +ve Culture ve Non-infective
Echo
S. viridans (>35%) Haemophilus SLE
TTE detects vegetations > 2mm
S. bovis Actinobacillus Marantic
TOE is more sensitive (90-100% vs. 50-60%)
S. aureus Cardiobacterium
S. epidermidis Eikenella
Enterococci Kingella
Pseudomonas Coxiella Rx
Chlamydia Empiric
Acute severe: Fuclox + gent IV
Subacute: Benpen + gent IV
Clinical Features
Sepsis Embolic phenomena
Streps: benpen + gent IV
Fever, rigors Abscesses in brain, heart,
Enterococci: amoxicillin + gent IV
Night sweats kidney, spleen, gut and
lung (if right-sided) Staphs: fluclox rifampicin IV
Wt. loss
Janeway lesions Fungi: flucytosine IV + fluconazole PO.
Anaemia
Amphotericin if flucytosine resistance or
Splenomegaly
Immune complex deposition Aspergillus.
Clubbing
Micro haematuria due to
GN Consider surgery if
Cardiac
Heart failure
New/changing murmur Vasculitis
Emboli
(MR: 85%, AR: 55%) Roth spots
Valve obstruction
AV block Splinter haemorrhages
Prosthetic valve
LVF Oslers nodes
Roth spots: boat-shaped retinal haemorrhages c pale centre Prophylaxis

Janeway lesions: painless palmer macules Abx prophylaxis solely to prevent IE not recommended
Oslers nodes: painful, purple papules on finger pulps
Dx: Duke Criteria Mortality

30% c staphs
Major 14% c bowel flora
1. +ve blood culture
6%
c sensitive streps
Typical organism in 2 separate cultures, or
Persistently +ve cultures, e.g. 3, >12h apart
2. Endocardium involved
+ve echo (vegetation, abscess, valve dehiscence)
or
New valvular regurgitation
Minor
1. Predisposition: cardiac lesion, IVDU
2. Fever >38
3. Emboli: septic infarcts, splinters, Janeway lesions
4. Immune phenomenon: GN, Osler nodes, Roth spots, RF
5. +ve blood culture not meeting major criteria
Dx if:
2 major
1 major + 3 minor
All 5 minor

Rheumatic Fever
Aetiology Ix
Group A -haemolytic strep. (pyogenes)
Bloods
Epidemiology Strep Ag test or ASOT
5-15yrs FBC, ESR/CRP
Rare in West. Common in developing world. ECG
Only 2% of population susceptible Echo
Pathophysiology
Ab cross-reactivity following S. pyogenes infection Rx
T2 hypersensitivity reaction (molecular mimicry). Bed rest until CRP normal for 2wks
Abs. vs. M protein in cell wall. Benpen 0.6-1.2mg IM for 10 days
Cross react
c myosin, muscle glycogen and SM cells. Analgesia for carditis/arthritis: aspirin / NSAIDs
Path: Aschoff bodies and Anitschkow myocytes. Add oral pred if: CCF, cardiomegaly, 3rd degree block
Chorea: Haldol or diazepam
Dx: revised Jones Criteria
Evidence of GAS infection plus:
2 major criteria, or Prognosis
1 major + 2 minor Attacks last ~ 3mo.
60% c carditis develop chronic rheumatic heart
Evidence of GAS infection disease.
+ve throat culture Recurrence ppted by
Rapid strep Ag test Further strep infection
ASOT or DNase B titre Pregnancy
Recent scarlet fever OCP
Valve disease: regurgitation stenosis
Major Criteria Mitral (70%)
Pancarditis Aortic (40%)
Arthritis Tricuspid (10%)
Subcutaneous nodules Pulmonary (2%)
Erythema marginatum
Sydenhams chorea
Secondary Prophylaxis
Minor criteria Prevent recurrence
Fever Pen V 250mg/12h PO
ESR or CRP Carditis + valve disease: until 40yrs old
Arthralgia (not if arthritis is major) Carditis w/o valve disease:10yrs
Prolonged PR interval (not if carditis is a major) No carditis: 5yrs
Prev rheumatic fever
Symptomatology
Pancarditis (60%)
Pericarditis: chest pain, friction rub
Myocarditis: sinus tachy, AV block, HF, CK, T
inversion
Endocarditis: murmurs
MR, AR, Carey Coombs (MDM)
Arthritis (75%)
Migratory polyarthritis of large joints (esp. knees)
Subcutaneous nodules (2-20%)

Small mobile, painless nodules on extensor surfaces
(esp. elbows)
Erythema marginatum (2-10%)

Red, raised edges c central clearing.
Trunk, thighs and arms.
Sydenhams Chorea (10%)

Occurs late
Grimacing, clumsy, hypotonia (stops in sleep)

Pericardial Disease
Acute Pericarditis Pericardial Effusion

Causes
Causes
Any cause of pericarditis
Viral: coxsackie, flu, EBV, HIV
Bacterial: pneumonia, rheumatic fever, TB, staphs
Clinical Features
Fungi Dyspnoea
MI, Dresslers JVP (prominent x descent)
Drugs: penicillin, isoniazid, procainamide, hydralazine
Bronchial breathing @ left base
Other: uraemia, RA, SLE, sarcoid, radiotherapy Ewarts sign: large effusion compressing left lower
lobe
Clinical Features Signs of cardiac tamponade may be present.
Central / retrosternal chest pain
Sharp Ix
Pleuritic
CXR: enlarged, globular heart
Worse lying down
ECG
Relieved by sitting forward
Low-voltage QRS complexes
Radiates to left shoulder
Alternating QRS amplitude (electrical alterans)
Pericardial friction rub.
Echo: echo-free zone around heart
Fever
Signs of effusion / tamponade Mx
Treat cause
Ix
Pericardiocentesis may be diagnostic or therapeutic
ECG: saddle-shaped ST-elevation PR depression
Culture, ZN stain, cytology
Bloods: FBC, ESR, trop (may be ), cultures, virology
Mx
Analgesia: ibuprofen 400mg/8h PO
Rx cause
Consider steroids / immunosuppression
Constrictive Pericarditis
Heart encased in a rigid pericardium. Tamponade
Accumulation of pericardial fluid intra-pericardial
Causes pressure poor ventricular filling CO
Often unknown
May occur after any pericarditis Causes
Any cause of pericarditis
Clinical features Aortic dissection
RHF c JVP (prominent x and y descents) Warfarin
Kussmauls sign: JVP c inspiration Trauma
Quiet heart sounds
Signs
S3
Becks Triad: BP, JVP, quiet heart sounds
Hepatosplenomegaly
Pulsus paradoxus: pulse fades on inspiration
Ascites, oedema
Kussmauls sign
Ix
Ix
CXR: small heart + pericardial calcification
ECG: low-voltage QRS electrical alternans
Echo
CXR: large, globular heart
Cardiac Catheterisation
Echo: diagnostic, echo-free zone around heart
Mx
Mx
Surgical excision
Urgent pericardiocentesis
20ml syringe + long 18G cannula
O
45 , just left of xiphisternum, aiming for tip of left
scapula.
Aspirate continuously and watch ECG.
Treat cause
Send fluid for cytology, ZN stain and culture

Myocardial Disease
Acute Myocarditis Cardiac Myxoma
Rare, benign cardiac tumour
Causes F>M=2:1
Idiopathic (~50%) May be familial: e.g. Carney Complex
Viral: coxsackie B, flu, HIV Cardiac and cutaneous myxoma, skin
Bacterial: S. aureus, syphilis pigmentation, endocrinopathy (e.g. Cushings)
Drugs: cyclophosphamide, Herceptin, CBZ, phenytoin 90% in left atrium (fossa ovalis)
Autoimmune: Giant cell myocarditis assoc.
c SLE Features:
Clubbing, fever, wt., ESR
Symptoms Signs similar to MS (MDM, systemic emboli, AF)
Flu-like prodrome: fever, sore throat, myalgia but vary c posture.
Dyspnoea, fatigue Dx: Echo
Chest pain (may coexist
c Bornholm disease) Rx: Excision
Arrhythmia palpitations
Restrictive Cardiomyopathy
Signs
Soft S1 Causes: miSSHAPEN
S4 gallop Sarcoid
Systemic sclerosis
Ix Haemochromatosis
ECG Amyloidosis
ST-elevation or depression Primary: endomyocardial fibrosis
T wave inversion Eosinophilia (Lofflers eosinophilic endocarditis)
Transient AV block Neoplasia: carcinoid ( TR and PS)
Bloods: +ve trop, CK
Clinical Features: as constrictive pericarditis
Mx
Supportive Dx: Catheterisation
Rx cause
Rx: Rx cause
Hypertrophic Obstructive Cardiomyopathy

LVOT obstruction from asymmetric septal hypertrophy Dilated Cardiomyopathy
AD inheritance (but 50% sporadic)
-myosin heavy chain mutation commonest Causes: DILATE
Ask re family Hx of sudden death Dystophy: muscular, myotonic, glycogen storage disease
Infection: complication of myocarditis
Symptoms Late pregnancy: peri-, post-partum
Angina Autoimmune: SLE
Dyspnoea Toxins: EtOH, doxorubicin, cyclophosphamide, DXT
Palpitations: AF, WPW, VT Endocrine: thyrotoxicosis
Exertional syncope or sudden death
Presentation
Signs LVF and RVF
Jerky pulse Arrhythmias
Double apex beat
Harsh ESM @ LLSE
c systolic thrill Signs
S4 JVP
Displaced apex
Ix S3 gallop
ECG BP
LVH/LAD/L strain, MR/TR
Ventricular ectopics, VT, VF
Echo: ASH Ix
Exercise test holter monitor to quantify risk CXR: cardiomegaly, pulmonary oedema
ECG: T inversion, poor progression
Mx Echo: globally dilated, hypokinetic heart + EF
Medical Catheter + biopsy: myocardial fibre disarray
st nd
-ve inotropes: 1 -B, 2 verapamil
Amiodarone: arrhythmias Mx
Anticoagulate if AF or emboli Bed rest
Non-medical Medical: diuretics, ACEi, digoxin, anticoagulation
Septal myomectomy (surgical or chemical) if Non-medical: biventricular pacing, ICD
severe symptoms Surgical: heart Tx
Consider ICD
Congenital Heart Disease
Bicuspid Aortic Valve Ventricular Septal Defect
No problems @ birth Hole connects ventricles
Most eventually develop stenosis regurgitation
Pre-disposes to IE/SBE Causes
Congenital
Acquired: post-MI
Atrial Septal Defect
Hole connects the atria Presentation
Secundum defects high in the septum are commonest Severe HF in infancy or incidental discovery in later life
Often asympto until adulthood
LV compliance c age LR shunt Signs
Small holes which are haemodynamically less significant
Symptoms louder murmurs
Dyspnoea Harsh, pansystolic murmur @ left sternal edge
Pulmonary HTN Systolic thrill
Left parasternal heave
Arrhythmia
Larger holes PHT
Chest pain
Complications
Signs
AF
PHT
JVP
Eisenmengers
Pulmonary ESM
PHT TR or PR
ECG
Small: normal
Complications
Large: LVH + RVH
Paradoxical emboli
Eisenmengers syndrome
CXR
RA pressure: RL shunt cyanosis
Small: mild pulmonary plethora
Ix Large: cardiomegaly + marked pulmonary plethora
ECG:
Rx
Secundum: RAD
Surgical closure indicated if symptomatic VSD
c large
CXR: pulmonary plethora
shunt.
Echo: diagnostic
Rx
Transcatheter closure Fallots Tetralogy
Recommended in adults if high pulmonary to systemic Commonest congenital cyanotic heart defect
blood flow ratio (1.5:1) Abnormal separation of truncus arteriosus into aorta and
pulmonary arteries.
Coarctation of the Aorta Pathology

Congenital narrowing of the aorta 1. VSD
Usually occurs just distal to origin of left subclavian 2. Pulmonary stenosis
M>F 3. RVH
4. Overriding aorta
Associations
Associations
Bicuspid aortic valve
Di George: CATCH-22
Turners syndrome
Presentation
Signs
Infants: hypercyanotic episodes, squatting, clubbing
Radio-femoral delay + weak femoral pulse
Adult
Hypertension
Often asympto
Systolic murmur / bruit heard best over left scapula
Unoperated: cyanosis, ESM of PS
Repaired: dyspnoea, palpitations, RVF
Complications
Heart failure ECG: RVH + RBBB
IE CXR: Coeur en sabot
Echo: anatomy + degree of stenosis
Ix
CXR: rib notching Rx: Surgical (usually before 1yr)
ECG: LV strain Closure of VSD
CT angiogram Correction of the pulmonary stenosis
Rx: balloon dilatation + stenting
Inherited Connective Tissue Disorders
Marfans Syndrome Ehlers-Danlos Syndrome
Epidemiology Pathogenesis
Autosomal dominant Rare heterogeneous group of collagen disorders.
Spontaneous mutation in 25% 6 subtypes
c varying severity
M=F Commonest types (1 and 2) are autosomal dominant
Prevalence = 1/5000
Presentation
Pathophysiology Hyperelastic skin
Mutation in FBN1 gene on Chr 5 Hypermobile joints
Encodes fibrillin-1 glycoprotein Cardiac: MVP, AR, MR and aneurysms
Fibrillin-1 is an essential component of elastin Fragile blood vessels easy bruising, GI bleeds
Histology: cystic medial necrosis Poor healing
Presentation Differential Diagnosis

Cardiac Cutis Laxa: loose skin + hypermobile joints
Aortic aneurysm and dissection Pseudoxanthoma elasticum: skin laxity
Aortic root dilatation regurgitation Marfans
MV prolapse regurgitation
Ocular
Lens dislocation: superotemporal
MSK
High-arched palate
Arachnodactyly
Arm-span > height
Pectus excavatum
Scoliosis
Pes planus
Joint hypermobility
Complications
Ruptured aortic aneurysm
Spontaneous pneumothorax
Diaphragmatic hernia
Hernias
Dx
Two 2/3 organ systems must be involved
Differential Diagnosis
MEN-2b
Homocystinuria
Ehlers-Danlos
Ix
Slit-lamp examination: ectopia lentis
CXR
Widened mediastinum
Scoliosis
Pneumothorax
ECG
Arrhythmias: premature atrial and ventricular
ectopics
Echo
Aortic root dilatation AR
MVP and MR
MRI: dural ectasia (dilation of neural canal)
Genetic testing: FBN-1 mutation
Mx
Refer to ortho, cardio and ophtho
Life-style alteration: cardiointensive sports
Beta-blockers slow dilatation of the aortic root
Regular cardiac echo
Surgery when aortic root 5cm wide
Pulmonology
Contents
Clubbing ...................................................................................................................................................................................... 36
Cyanosis ...................................................................................................................................................................................... 36
Pneumonia .................................................................................................................................................................................. 37
Complications of Pneumonia ....................................................................................................................................................... 38
Systemic Inflammatory Response Syndrome ............................................................................................................................. 38
Specific Pneumonias ................................................................................................................................................................... 39
Bronchiectasis ............................................................................................................................................................................. 40
Cystic Fibrosis ............................................................................................................................................................................. 41
Pulmonary Aspergillus Infections ................................................................................................................................................ 42
Lung Cancer: Presentation .......................................................................................................................................................... 43
Lung Cancer: Investigation and Management ............................................................................................................................ 44
ARDS ........................................................................................................................................................................................... 45
Respiratory Failure ...................................................................................................................................................................... 46
Oxygen Therapy .......................................................................................................................................................................... 46
Chronic Asthma ........................................................................................................................................................................... 47
Acute Severe Asthma .................................................................................................................................................................. 48
COPD .......................................................................................................................................................................................... 49
Acute Exacerbation of COPD ...................................................................................................................................................... 50
Pulmonary Embolism................................................................................................................................................................... 51
Pneumothorax ............................................................................................................................................................................. 52
Pleural Effusion ........................................................................................................................................................................... 53
Sarcoidosis .................................................................................................................................................................................. 54
Interstitial Lung Disease .............................................................................................................................................................. 55
Extrinsic Allergic Alveolitis ........................................................................................................................................................... 56
Industrial Lung Disease ............................................................................................................................................................... 56
Idiopathic Pulmonary Fibrosis (CFA)........................................................................................................................................... 56
Pulmonary Hypertension ............................................................................................................................................................. 57
Cor Pulmonale ............................................................................................................................................................................. 57
Obstructive Sleep Apnoea ........................................................................................................................................................... 58
Smoking Cessation...................................................................................................................................................................... 58

Clubbing Cyanosis
Features and Stages Definition
1. Bogginess / fluctuance of nail bed Blue discoloration of mucosal membranes or skin
2. Loss of concave nail fold angle Deoxygenated Hb >5g/dl
3. longitudinal and transverse curvature
4. Soft tissue expansion at distal phalanx (drumstick) Classification
Peripheral: cold, blue nails
Causes Central: blue tongue, lips
Respiratory Causes
Carcinoma Think of O2 cascade
Bronchial
Mesothelioma
Respiratory
Chronic lung suppuration Hypoventilation: COPD, MSK
Empyema, abscess
diffusion: pulm oedema, fibrosing alveolitis
Bronchiectasis, CF
V/Q mismatch: PE, AVM (e.g. HHT)
Fibrosis
Idiopathic pulmonary fibrosis / CFA
Cardiac
TB
Congenital: Fallots, TGA
Cardiac CO: MS, systolic LVF
Infective Endocarditis Vascular: Raynauds, DVT
Congenital cyanotic heart disease
RBCs
Atrial myxoma
Low affinity Hb, may be hereditary or acquired
GIT
Cirrhosis
Crohns, uC
Coeliac
Cancer: GI lymphoma
Other
Familial
Thyroid Acropachy
Upper limb AVMs or aneurysms
Unilateral clubbing

Pneumonia
Epidemiology Ix
Incidence: 1/100 Bloods: FBC, U+E, LFT, CRP, culture, ABG (if SpO2)
Mortality: 10% in hospital, 30% in ITU Urine: Ag tests (Pneumococcal, Legionella)
Sputum: MC&S
Anatomic Classification Imaging: CXR
infiltrates, cavities, effusion
Bronchopneumonia Special
Patchy consolidation of different lobes Paired sera Abs for atypicals
Mycoplasma, Chlamydia, Legionella
Lobar Pneumonia Immunofluorescence (PCP)
Fibrosuppurative consolidation of a single lobe BAL
Congestion red grey resolution Pleural tap
Severity: CURB-65 (only if x-ray changes)

Confusion (AMT 8) Score
Urea >7mM 0-1 home Rx
Resp. rate >30/min 2 hospital Rx
BP <90/60 3 consider ITU
65
Mx
Abx
O2: PaO28, SpO2 94-98%
Fluids
Aetiological Classification
Analgesia
Community Acquired Pneumonia Chest physio
Pneumococcus, mycoplasma, haemophilus Consider ITU if shock, hypercapnoea, hypoxia
S. aureus, Moraxella, Chlamydia, Legionella F/up @ 6wks c CXR
Viruses: 15% Check for underlying Ca
Hospital Acquired Pneumonia Empirical Abx

>48hrs after hospital admission
Gm-ve enterobacteria, S. aureus CAP
Aspiration Mild amoxicillin 500mg TDS PO for 5d or

Risk: stroke, bulbar palsy, GCS, GORD, achalasia clarithro 500mg BD PO for 7d
Anaerobes
Mod amoxicillin 500mg TDS and clarithro 500mg BD PO/IV
Immunocompromised (clarithro alone if pen allergy) for 7d
The usual suspects, plus
PCP, TB, fungi, CMV/HSV Sev Co-amoxiclav 1.2g TDS IV / cefuroxime 1.5g TDS IV
and clarithro 500mg BD IV for 7-10d
Add fluclox if staph suspected.
Symptoms Atyp Chlamydia: tetracycline

Fever, rigors PCP: Co-trimoxazole
Malaise, anorexia Legionella: Clarithro + rifampicin
Dyspnoea
Cough, purulent sputum, haemoptysis HAP
Pleuritic pain Mild / <5d: Co-amoxiclav 625mg PO TDS for 7d
Severe / >5d: Tazocin vanc gent for 7d
Aspiration
Signs
Co-amoxiclav 625mg PO TDS for 7d
RR, HR
Cyanosis
Confusion
Pneumovax (23 valent)
65yrs
Consolidation
expansion Chronic HLKP failure or conditions
Dull percussion DM
Bronchial breathing Immunosuppression: hyposplenism, chemo, HIV
air entry CI: P, B, fever
Crackles
Pleural rub NB. revaccinate every 6yrs
VR
Complications of Pneumonia Systemic Inflammatory Response
Syndrome
Respiratory failure
Type 1: PaO2 <8kPa + PaCO2 <6kPa Inflammatory response to a variety of insults
Type 2: PaO2 <8kPa + PaCO2 >6kPa
Mx: O2 therapy, ventilation
manifest by 2 of:
Temperature: >38C or <36C
Heart rate: >90
Hypotension
Respiratory rate: >20 or PaCO2 <4.6 KPa
Cause: dehydration + septic vasodilatation
WCC: >12x109/L or <4 x109/L or >10% bands
Mx
If SBP<90 250ml fluid challenge over 15min
If no improvement: central line + IV fluids
If refractory: ITU for inotropes Sepsis
SIRS caused by infection
AF
Usually resolves
c Rx
Mx: Digoxin or -B for rate control Severe Sepsis
Sepsis
c at least 1 organ dysfunction or hypoperfusion
Pleural effusion
Exudate
Mx: tap and send for MC+S, cytology and chemistry Septic Shock
Severe sepsis with refractory hypotension
Empyema
Pus in the pleural cavity
Anaerobes, Staph, Gm-ve MODS
Assoc. c recurrent aspiration Impairment of 2 organ systems
Pt.
c resolving pneumonia develops recurrent fever Homeostasis cannot be maintained without therapeutic
Tap: turbid, pH<7.2, glucose, LDH intervention.
Mx: US guided chest drain + Abx
Lung Abscess
Causes
Aspiration
Bronchial obstruction: tumour, foreign body
Septic emboli: sepsis, IVDU, RH endocarditis
Pulmonary infarction
Subphrenic / hepatic abscess
Features
Swinging fever
Cough, foul purulent sputum, haemoptysis
Malaise, wt. loss
Pleuritic pain
Clubbing
Empyema
Tests
Blood: FBC, ESR, CRP, cultures
Sputum: micro, culture, cytology
CXR: cavity
c fluid level
Consider CT and bronchoscopy
Mx
Abx according to sensitivities
Aspiration
Surgical excision
Other Complications
Sepsis
Pericarditis / myocarditis
Jaundice
Usually cholestatic
Causes: sepsis, drugs (fluclox, Augmentin),
Mycoplasma, Legionella
Specific Pneumonias
Organism Risk Factors Pulmonary Features Extrapulmonary Mx
Pneumococcus Elderly Lobar consolidation Herpes labialis Amoxicillin
EtOH Benpen
Immunosuppressed Cephalosporins
CHF
Pulmonary disease
S. aureus Influenza infection Bilateral cavitating Fluclox
IVDU bronchopneumonia Vanc
Co-morbidities
Klebsiella Rare Cavitating pneumonia Cefotaxime
Elderly Esp. upper lobes
EtOH
DM
Pseudomonas Bronchiectasis Taz
CF
Mycoplasma Epidemics Dry cough Flu-like prodrome Dx: serology
- headache
Reticulo-nodular shadowing or - myalgia/arthralgia Clarithro
patchy consolidation Cipro
Cold agglutinins AIHA
Cryoglobulin
Erythema multiforme
SJS
GBS
Hepatitis
Legionella Travel Dry cough Flu-like prodrome Lymphopenia
Air conditioning Dyspnoea Na+
Anorexia Deranged LFTs
Bi-basal consolidation D&V
Hepatitis Dx: Urinary Ag or
Renal Failure serology
Confusion
SIADH Na Clarithro rifa
Chlam. Pharyngitis, otitis pneumonia Sinus pain Dx: serology
pneumoniae Clarithro
Chlam. psittaci Parrots Dry cough Horders spots ~ rose spots Dx: serology
Patchy consolidation Splenomegaly
Epistaxis Clarithro
Hepatitis, nephritis
Meningo-encephalitis
PCP Immunocompromised Dry cough Dx: visualisation
Exertional dyspnoea from BAL,
Bilateral creps sputum, biopsy
CXR: normal or bilateral perihilar High dose co-

interstitial shadowing trimoxazole or
pentamidine
Prophylaxis if
CD4<200 or after
st
1 attack

Bronchiectasis
Pathophysiology Complications
Chronic infection of bronchi/bronchioles permanent Pneumonia
dilatation. Pleural effusion
Retained inflammatory secretions and microbes Pneumothorax
airway damage and recurrent infection Pulmonary HTN
Organisms: Massive haemoptysis
H. influenza Cerebral abscess
Pneumococcus Amyloidosis
S. aureus
Pseudomonas
Ix
Sputum MCS
Causes
Blood: Se Ig, Aspergillus precipitins, RF, 1-AT level
Idiopathic in 50%
Test Ig response to pneumococcal vaccine
CXR: thickened bronchial walls (tramlines and rings)
Congenital
Spirometry: obstructive pattern
CF (mainly upper lobe infiltration)
HRCT chest
Kartageners / PCD
Dilated and thickened airways
Youngs syn. (azoopermia + bronchiectasis)
Saccular dilatations in clusters c pools of mucus
Post-infectious Bronchoscopy + mucosal biopsy
Measles Focal obstruction
PCD
Pertussis
CF sweat test (pilocarpine iontopheresis)
Pneumonia
TB
Bronchiolitis
Rx
Immunodeficiency Chest physio: expectoration, drainage, pulm. rehab
Hypogammaglobulinaemia Abx for exacerbations: e.g. cipro for 7-10d
X-linked agammaglobulinaemia: Brutons Bronchodilators: nebulised agonists
CVID Treat underlying cause
IgG subclass deficiency CF: DNAase
IgA deficiency ABPA: Steroids
Immune deficiency: IVIg
Other Surgery may be indicated in severe localised disease
Bronchial obstruction: LNs, tumour, foreign body
ABPA
RA
UC
Yellow nail syndrome
Yellow nail discoloration and dystrophy
Lymphoedema
Pleural effusions
Bronchiectasis
Symptoms
Persistent cough
c purulent sputum
Haemoptysis (may be massive)
Fever, wt. loss
Signs
Clubbing
Coarse inspiratory creps
Wheeze
Purulent sputum
Cause
Situs inversus (+ PCD = Kartageners syn.)
Splenomegaly: immune deficiency

Cystic Fibrosis
Pathogenesis Ix
Auto recessive, 1:2000 live Caucasian births Bloods: FBC, LFTs, clotting, ADEK levels, glucose TT
Mutation in CFTR gene on Chr 7 (commonly F508) Sputum MCS
luminal Cl secretion and Na reabsorption CXR: bronchiectasis
viscous secretions. Abdo US: fatty liver, cirrhosis, pancreatitis
In sweat glands, Cl and Na reabsorption salty sweat Spirometry: obstructive defect
Aspergillus serology / skin test (20% develop ABPA)
Clinical Features
Mx
Neonate
FTT General
Meconium ileus MDT: physician, GP, physio, dietician, specialist nurse
Rectal prolapse
Chest
Children / Young Adults Physio: postural drainage, forced expiratory techniques
Nose: nasal polyps, sinusitis Abx: acute infections and prophylaxis
Resp: cough, wheeze, infections, bronchiectasis, Mucloytics: DNAse
haemoptysis, pneumothorax, cor pulmonale Bronchodilators
GI: Vaccinate
Pancreatic insufficiency: DM, steatorrhoea
Distal Intestinal Obstruction Syndrome GI
Gallstones Pancreatic enzyme replacement: pancreatin (Creon)
O
Cirrhosis (2 biliary) ADEK supplements
Other: male infertility, osteoporosis, vasculitis
Insulin
Ursodeoxycholic acid for impaired hepatic function
Signs
Stimulates bile secretion
Clubbing HPOA
Cyanosis Advanced Lung Disease
Bilateral coarse creps O2
Diuretics (Cor pulmonale)
NIV
Common Respiratory Organisms Heart/lung transplantation
Early
S. aureus Other
H. influenza Rx of complications: e.g. DM
Late Fertility and genetic counselling
P. aeruginosa: 85% DEXA osteoporosis screen
B. cepacia: 4%
Dx
Sweat test: Na and Cl > 60mM
Genetic screening for common mutations
Faecal elastase (tests pancreatic exocrine function)
Immunoreactive trypsinogen (neonatal screening)

Pulmonary Aspergillus Infections
Diseases
1. Asthma: T1HS reaction to spores
2. ABPA
3. Aspergilloma (mycetoma)
4. Invasive aspergillosis
5. Extrinsic allergic alveolitis
Allergic Bronchopulmonary Aspergillosis Invasive Aspergillosis

T1 and T3 HS reaction to Aspergillus fumigatus Aflatoxins liver cirrhosis and HCC (especially A.
Bronchoconstriction bronchiectasis flavus)
Symptoms Risk factors

Wheeze Immunocompromise: HIV, leukaemia, Wegeners
Productive cough Post-broad spectrum Abx
Dyspnoea
Ix
Ix CXR: consolidation, abscess
CXR: bronchiectasis Sputum MCS
Aspergillus in sputum (black on silver stain) BAL
Aspergillus skin test or IgE RAST +ve se precipitins
+ve se precipitins Serial galactomannan
IgE and eosinophils
Rx
Rx Voriconazole (better cf amphotericin)
Pred 40mg/d + itraconazole for acute attacks
Pred maintenance 5-10mg/d Prog
Bronchodilators for asthma 30% mortality
Aspergilloma (mycetoma) Extrinsic Allergic Alveolitis

Fungus ball within a pre-existing cavity Sensitivity to Aspergillus clavatus Malt workers lung
e.g. TB or sarcoid
Features
Usually asympto
Can haemoptysis (may be severe)
Lethargy, wt.
Ix
CXR: round opacity w/i a cavity, usually apical
Sputum culture
+ve se precipitins
Aspergillus skin test / RAST
Rx
Consider excision for solitary lesions / severe
haemoptysis

Lung Cancer: Presentation
Classification
Clinically, the most important distinction is between small-cell and non-small-cell (SCC, adeno and large-cell)
Type Epidemiology Pathology Behaviour

SCC 35% Centrally located Locally invasive
M>F Histo: Evidence of squamous differentiation Metastasise late (via LN)
Smoking - Keratinisation PTHrP Ca2+
Radon gas
Adeno 25% Peripherally located Extrathoracic mets common and early.
Females, Histo: Glandular differentiation - 80% present with mets
Non-smokers - Gland formation
Far East - Mucin production
Large-cell 10% Peripheral or central Poor prognosis
Histo: Large, poorly differentiated cells
Small-cell 20% Central location, near bronchi 80% present
c advanced disease
Smoking Histo: Small, poorly differentiated cells V. chemosensitive but v. poor prog
Ectopic hormone secretion
Other Lung Tumours: all rare Complications

Adenoma: 90% are carcinoid tumours
Hamartoma Local
Mesothelioma Recurrent laryngeal N. palsy
Phrenic N. palsy
SVC obstruction
Horners (Pancoasts tumour)
Epidemiology
AF
19% of all cancers
27% of cancer deaths (commonest) Paraneoplastic
Endo
+
ADH SIADH ( euvolaemic Na )
Symptoms ACTH Cushings syndrome
Cough and haemoptysis Serotonin carcinoid (flushing, diarrhoea)
Dyspnoea PTHrP 1O HPT (Ca2+, bone pain) SCC
Chest pain Rheum
Recurrent or slow resolving pneumonia Dermatomyositis / polymyositis
Anorexia and wt. Neuro
Hoarseness Purkinje Cells (CDR2) cerebellar degeneration
Peripheral neuropathy
Derm
Acanthosis nigricans (hyperpigmented body folds)
Signs Trousseau syndrome: thrombophlebitis migrans
Chest
Metastatic
Consolidation
Pathological #
Collapse
Hepatic failure
Pleural effusion
Confusion, fits, focal neuro
Addisons
General
Cachexia
Anaemia
Clubbing and HPOA (painful wrist swelling)
Supraclavicular and/or axillary LNs
Metastasis
Bone tenderness
Hepatomegaly
Confusion, fits, focal neuro
Addisons

Lung Cancer: Investigation and Management
Ix Mx
MDT: pulmonologist, oncologist, radiologist,
Bloods: FBC, U+E, Ca2+, LFTs histopathologist, cardiothoracic surgeon, specialist
Cytology: sputum, pleural fluid nurses, palliative care, GP
Assess risk of operative mortality: e.g. Thoracoscore
Imaging Cardiorespiratory function
CXR Co-morbidities
Coin lesion Advise smoking cessation
Hilar enlargement
Consolidation, collapse NSCLC
Effusion Surgical Resection
Bony secondaries Rx of choice for peripheral lesions c no metastatic
Contrast-enhanced Volumetric CT spread = stage I/II (~25%)
Staging: lower neck, chest, upper abdomen Need good cardiorespiratory function
Consider CT brain Wedge resection, lobectomy or pneumonectomy
PET-CT: exclude distant mets adjuvant chemo
Radionucleotide bone scan Curative radiotherapy
If cardiorespiratory reserve is poor
Biopsy Chemo radio for more advanced disease
Percutaneous FNA: peripheral lesions and LNs Platinum-based regimens
Bronchoscopy: biopsy and assess operability MAbs targeting EGFR (e.g. cetuximab) or TKI
Endoscopic bronchial US biopsy: mediastinal LNS (e.g. erlotinib)
Mediastinoscopy
SCLC
Lung Function Tests Typically disseminated @ presentation
Assess treatment fitness May respond to chemo but invariably relapse
CXR Coin Lesion Differential Palliation

Foreign body Radio: bronchial obstruction, haemoptysis, bone or CNS
Abscess: Staph, TB, Klebsiella, Mycetoma mets
Neoplasia (1O or 2O) SVC obstruction: stenting + radio + dexamethasone
Granuloma: RA, Wegeners, TB, Sarcoid Endobronchial therapy: stenting, brachytherapy
Structural: AVM Pleural drainage / pleurodesis
Analgesia
TNM Staging for NSCLC

Prognosis
Tx Malignant cells in bronchial secretions NSCLC: 50% 5ys w/o spread; 10% c spread
Tis CIS SCLC: 1-1.5yrs median survival treated; 3mo untreated
T0 None evident
T1 3cm, in lobar or more distal airway
T2 >3cm and >2cm from carina or pleural involvement
T3 <2cm from carina or involves chest wall, diaphragm
T4 Involves mediastinum or malignant effusion is present
N0 None involved
N1 Peribronchial or ipsilateral hilum
N2 Ipsilateral mediastinum
N3 Contralateral hilum or mediastinum or supraclavicular

ARDS
Pathogenesis Causes
May result from direct pulmonary insult or be 2O to
severe systemic illness. Pulmonary
Inflam mediators capillary permeability and non- Pneumonia
cardiogenic pulmonary oedema. Aspiration
Inhalation injury
Contusion
Clinical Features
Tachypnoea Systemic
Cyanosis Shock
Bilateral fine creps Sepsis
SIRS Trauma
Haemorrhage and multiple transfusions
Pancrea0titis
Ix Acute liver failure
Bloods: FBC, U+E, LFTs, clotting, amylase, CRP, DIC
cultures, ABG. Obs: eclampsia, amniotic embolism
CXR: bilateral perihilar infiltrates Drugs: aspirin, heroin
Dx Differential Dx of Pulmonary Oedema

Acute onset
CXR shows bilateral infiltrates Tranusdates
No evidence of congestive cardiac failure capillary hydrostatic pressure
CCF
PaO2:FiO2 <200
Iatrogenic fluid overload
Renal failure
Relative in negative pressure pulmonary
Mx oedema
Admit to ITU for organ support and Rx underlying cause capillary oncotic pressure
Liver failure
Ventilation Nephrotic syndrome
Indications Malnutrition, malabsorption, protein-losing
PaO2<8KPa despite 60% FiO2 enteropathy
PaCO2>6KPa interstitial pressure
Method lymphatic drainage: e.g. Ca
6ml/kg + PEEP (e.g. 10cm H2O)
SEs Exudates
VILI ARDS
VAP
Weaning difficulty
Circulation
Invasive BP monitoring
Maintain CO and DO2 c inotropes
E.g. norad or dobutamine
RF may require haemofiltration
Sepsis
Abx
Other
Nutritional support: enteral (best), TPN
Prognosis
50-75% mortality

Respiratory Failure
Type 1 Clinical Features
PaO2 <8KPa and PaCO2 <6KPa
V/Q mismatch and diffusion failure Hypoxia
Acute
Dyspnoea
Type 2 Agitation
PaO2 <8KPa and PaCO2 >6KPa Confusion
Alveolar hypoventilation V/Q mismatch Cyanosis
Chronic
Polycythaemia
PHT
Causes cor pulmonale
V/Q Mismatch (A-a gradient) Hypercapnoea

Vascular Headache
PE Flushing and peripheral vasodilatation
PHT Bounding pulse
Pulmonary Shunt (R L) Flap
Asthma (early) Confusion coma
Pneumothorax
Atelectasis
Mx: Rx underlying cause
Alveolar Hypoventilation
Type 1
Obstructive
Give O2 to maintain SpO2 94-98%
COPD
Asthma Assisted ventilation if PaO2<8KPa despite 60% O2
Bronchiectasis
Bronchiolitis Type 2
Intra- and Extra-thoracic (Ca, LN, epiglottitis) Controlled O2 therapy @ 24% O2 aiming for SpO2 88-92%
Restrictive and a PaO2 >8kPa
drive: CNS sedation, trauma, tumour Check ABG after 20min
NM disease: cervical cord lesion, polio, GBS, If PaCO2 steady or lower can FiO2 if necessary
MG If PaCO2 >1.5KPa and pt. still hypoxic, consider
Chest: flail, kyphoscoliosis, obesity NIV or respiratory stimulant (e.g. doxapram)
Fluid and fibrosis
Diffusion Failure (A-a gradient)

Oxygen Therapy
Fluid
Pulmonary oedema Principles
Pneumonia Critically ill pts. should receive high conc O2 immediately.
Infarction O2 should be prescribed to achieve target SpO2
Blood 94-98% for most patients
Fibrosis 88-92% for those at risk or hypercapnic resp failure
In pts. at risk of hypercapnic resp failure:
NB. Both fluid and fibrosis also V/Q mismatch and Start O2 therapy at 24% and do an ABG
alveolar hypoventilation due to compliance Blue Venturi @ 2-4L/min
Clinically: RR c O2 may be useful sign
If PCO2 6kPa: target SpO2 to 94-98%
A-a Gradient If PCO2 >6kPa: maintain target SpO2
PAO2= (95 x FiO2) (PaCO2/0.8)
(PAO2-PaO2) suggests lung pathology Mechanisms
Nasal Prongs: 1-4L/min = 24-40% O2
Simple Face Mask
Non-rebreathing Mask
Reservoir bag allows delivery of high concentrations of O2.
60-90% at 10-15L
Venturi Mask
Provide precise O2 concentration at high flow rates
Yellow: 5%
White: 8%
Blue: 24%
Red: 40%
Green: 60%
Chronic Asthma
Definition Differential
Episodic, reversible airway obstruction due to Pulmonary oedema (cardiac asthma)
bronchial hyper-reactivity to a variety of stimuli. COPD
Epidemiology Ix
Incidence 5-8% ( in children vs. adults)
Peaks at 5yrs, most outgrow by adolescence Bloods
FBC (eosinophila)
IgE
Pathophysiology
Aspergillus serology
Acute (30min)
Mast cell-Ag interaction histamine release
CXR: hyperinflation
Bronchoconstriction, mucus plugs, mucosal swelling
Spirometry
Chronic (12h)
Obstructive pattern
c FEV1:FVC < 0.75
TH2 cells release IL-3,4,5 mast cell, eosinophil and
15% improvement in FEV1 c -agonist
B cell recruitment
Airway remodelling
PEFR monitoring / diary
Diurnal variation >20%
Causes Morning dipping
Atopy Atopy: skin-prick, RAST
T1 hypersensitivity to variety of antigens
Dust mites, pollen, food, animals, fungus
Mx
Stress
Cold air General Measures: TAME
Viral URTI Technique for inhaler use
Exercise Avoidance: allergens, smoke (ing), dust
Emotion Monitor: Peak flow diary (2-4x/d)
Educate
Toxins Liaise
c specialist nurse
Smoking, pollution, factory Need for Rx compliance
Drugs: NSAIDS, -B Emergency action plan
Symptoms Drug Ladder

Cough sputum (often at night)
Wheeze 1 SABA PRN
Dyspnoea If use >1/d or nocte symptoms step 2
Diurnal variation
c morning dipping
2 Low-dose inhaled steroid: beclometasone 100-400ug bd
Hx
3 LABA: salmeterol 50ug bd
Precipitants
Good response: continue
Diurnal variation
Benefit but control still poor: steroid to 400ug bd
Exercise tolerance
No benefit: discontinue + steroid to 400ug bd
Life effects: sleep, work
Other atopy: hay fever, eczema If control is still poor consider trial of:
Home and job environment Leukotriene receptor antagonist (e.g. monetelukast)
Esp. if exercise- / NSAID-induced asthma
Signs SR Theophylline
Tachypnoea, tachycardia
Widespread polyphonic wheeze 4 Trials of
Hyperinflated chest inhaled steroid to up to 1000ug bd
air entry Leukotriene receptor antagonist
Signs of steroid use SR Theophylline
MR agonist PO
Associated Disease 5 Oral steroids: e.g. prednisolone 5-10mg od

GORD Use lowest dose necessary for symptom control
Churg-Strauss Maintain high-dose inhaled steroid
ABPA Refer to asthma clinic

Acute Severe Asthma
Presentation Mx
Acute breathlessness and wheeze
O2, Nebs and Steroids
Hx 1. Sit-up
Precipitant: infection, travel, exercise? 2. 100% O2 via non-rebreathe mask (aim for 94-98%)
Usual and recent Rx? 3. Nebulised salbutamol (5mg) and ipratropium (0.5mg)
Previous attacks and severity: ICU? 4. Hydrocortisone 100mg IV or pred 50mg PO (or both)
Best PEFR? 5. Write no sedation on drug chart
Ix
PEFR If Life Threatening
ABG Inform ITU
PaO2 usually normal or slightly MgSO4 2g IVI over 20min
PaCO2 Nebulised salbutamol every 15min (monitor ECG)
If PaCO2 : send to ITU for ventilation
FBC, U+E, CRP, blood cultures
If Improving
Assessment Monitor: SpO2 @ 92-94%, PEFR
Continue pred 50mg OD for 5 days
Severe: any one of
Nebulised salbutamol every 4hrs
PEFR <50%
RR >25
HR >110
Cant complete sentence in one breath IV Rx if No Improvement in 15-30min:
Nebulised salbutamol every 15min (monitor ECG)
Life Threatening: any one of
Continue ipratropium 0.5mg 4-6hrly
PEFR <33%
MgSO4 2g IVI over 20min
SpO2 <92%, PCO2 >4.6kPa, PaO2 <8kPa
Salbutamol IVI 3-20ug/min
Cyanosis
Consider aminophylline
Hypotension
Load: 5mg/kg IVI over 20min
Exhaustion, confusion
Unless already on theophylline
Silent chest, poor respiratory effort Continue: 0.5mg/kg/hr
Tachy-/brady-/arrhythmias Monitor levels
ITU transfer for invasive ventilation
Differential
Pneumothorax
Acute exacerbation of COPD
Pulmonary oedema Monitoring
PEFR every 15-30min
Pre- and post- agonist
Admission Criteria
SpO2: keep >92%
Life-threatening attack
ABG if initial PaCO2 normal or
Feature of severe attack persisting despite initial Rx
May discharge if PEFR > 75% 1h after initial Rx
Discharge When
Been stable on discharge meds for 24h
PEFR > 75% c diurnal variability < 20%
Discharge Plan
TAME pt.
PO steroids for 5d
GP appointment w/i 1 wk.
Resp clinic appointment w/i 1mo

COPD
Definition Ix
Airway obstruction: FEV1 <80%, FEV1:FVC <0.70 BMI
Chronic bronchitis: cough and sputum production on Bloods: FBC (polycythaemia), 1-AT level, ABG
most days for 3mo of 2 successive years. CXR
Emphysema: histological diagnosis of enlarged air Hyperinflation (> 6 ribs anteriorly)
spaces distal to terminal bronchioles
c destruction of Prominent pulmonary arteries
alveolar walls. Peripheral oligaemia
Bullae
Epidemiology ECG:
R atrial hypertrophy: P pulmonale
Prevalence: 10-20% of >40s
RVH, RAD
Spirometry: FEV1 <80%, FEV1:FVC <0.70, TLC, RV
Causes Echo: PHT
Smoking
Pollution
1ATD Chronic Rx
Assess Severity
Symptoms Mild: FEV1 >80% (but FEV/FVC <0.7 and symptomatic)
Cough + sputum Mod: FEV1 50-79%
Dyspnoea Severe: FEV1 30-49%
Wheeze Very Severe: FEV1 < 30%
Wt. loss
General Measures
Signs Stop smoking
Tachypnoea Specialist nurse
Prolonged expiratory phase Nicotine replacement therapy
Hyperinflation Bupropion, varenicline (partial nicotinic agonist)
Cricosternal distance (normal = 3 fingers) Support programme
Loss of cardiac dullness Pulmonary rehabilitation / exercise
Displaced liver edge Rx poor nutrition and obesity
Wheeze Screen and Mx comorbidities
May have early-inspiratory crackles e.g. cardiovasc, lung Ca, osteoporosis
Cyanosis Influenza and pneumococcal vaccine
Cor pulmonale: JVP, oedema, loud P2 Review 1-2x/yr
Signs of steroid use Air travel risky if FEV1<50%
Pink Puffers in emPhysema Mucolytics

alveolar ventilation breathless but not cyanosed Consider if chronic productive cough
Normal or near normal PaO2 E.g. Carbocisteine (CI in PUD)
Normal or low PaCO2
Progress T1 respiratory failure Breathlessness and/or exercise limitation
SABA and/or SAMA (ipratropium) PRN
Blue Bloaters in chronic Bronchitis SABA PRN may continue at all stages
alveolar ventilation cyanosed but not breathless
PaO2 and PaCO2: rely on hypoxic drive Exacerbations or persistent breathlessness
Progress T2 respiratory failure and cor pulmonale FEV1 50%: LABA or LAMA (tiotropium) (stop SAMA)
FEV1 <50%: LABA+ICS combo or LAMA
Persistent exacerbations or breathlessness

mMRC Dyspnoea Score LABA+LAMA+ICS
1. Dyspnoea only on vigorous exertion
Roflumilast / theophylline (PDIs) may be considered
2. SOB on hurrying or walking up stairs
Consider home nebs
3. Walks slowly or has to stop for breath
4. Stops for breath after <100m / few min
LTOT
5. Too breathless to leave house or SOB on dressing
Aim: PaO2 8 for 15h / day ( survival by 50%)
Clinically stable non-smokers
c PaO2 <7.3 (stable on
two occasions >3wks apart)
Complications
PaO2 7.3 8 + PHT / cor pulmonale / polycythaemia /
Acute exacerbations infection
nocturnal hypoxaemia
Polycythaemia
Terminally ill pts.
Pneumothorax (ruptured bullae)
Cor Pulmonale Surgery
Lung carcinoma Recurrent pneumothoraces
Isolated bullous disease
Lung volume reduction
Acute Exacerbation of COPD
Causes Management
Viral URTI (30%)
Also bacterial infections
Controlled O2 Therapy
Sit-up
Presentation 24% O2 via Venturi mask: SpO2 88-92%,
Cough + sputum Vary FiO2 and SpO2 target according to ABG
Breathlessness Aim for PaO2 >8 and in PCO2 of <1.5kPa
Wheeze
Hx
Smoking status Nebulised Bronchodilators
Exercise capacity Air driven
c nasal specs
Current treatment Salbutamol 5mg/4h
Previous exacerbations Ipratropium 0.5mg/6h
Ix
PEFR
Bloods: FBC, U+E, ABG, CRP, cultures Steroids (IV and PO)
Sputum culture Hydrocortisone 200mg IV
CXR: infection, pneumothorax Prednisolone 40mg PO for 7-14d
ECG
Differential
Abx
Pneumothorax
If evidence of infection
Pulmonary oedema
Doxy 200mg PO STAT then 100mg OD PO for 5d
PE
Asthma
NIV if no response:
Discharge Repeat nebs and consider aminophylline IV
Spirometry Consider NIV (BiPAP) if pH<7.35 and/or RR >30
Establish optimal maintenance therapy Consider invasive ventilation if pH<7.26
GP and specialist f/up Depends on pre-morbid state: exercise capacity,
Prevention using home oral steroids and Abx home O2, comorbidity
Pneumococcal and Flu vaccine
Home assessment

Pulmonary Embolism
Causes Management
Usually arise from DVTs in proximal leg or iliac veins
Rarely:
O2
Right ventricle post MI
Sit-up
Septic emboli in right sided endocarditis
100% O2 via non-rebreather mask
Risk Factors: SPASMODICAL
Sex: F
Pregnancy Analgesia
Age: Morphine metoclopramide if distressed
Surgery (classically 10d post-op straining at stool)
Malignancy
Oestrogen: OCP/HRT If critically ill c
massive PE consider thrombolysis
DVT/PE previous Hx
Immobility
Alteplase 50mg bolus stat
Colossal size (Surgical or interventional embolectomy)
Antiphospholipid Abs
Lupus Anti-coagulant
LMWH Heparin
Presentation e.g. enoxaparin 1.5mg/kg/24h SC
Symptoms and signs depend on size, number and
distribution of emboli
Symptoms SBP?
Dyspnoea
Pleuritic pain
Haemoptysis
<90 >90
Syncope
500ml colloid Start Warfarin
Confirm Dx
Signs
Fever
Cyanosis
Tachycardia, tachypnoea Inotropes if BP still
RHF: hypotension, JVP, loud P2 Dobutamine: aim for SBP >90
Evidence of cause: DVT Consider addition of NORAD
Consider thrombolysis (medical or surgical)
Ix
Bloods: FBC, U+E, clotting, D-dimers
ABG: normal or PaO2 and PaCO2, pH On-going Mx
CXR: normal or oligaemia, linear atelectasis
ECG: sinus tachycardia, RBBB, right ventricular strain TEDS stockings in hospital
(inverted T in V1-V4) Graduated compression stockings for 2yrs if DVT:
S1, Q3, T3 is rare prevent post-phlebitic syndrome (10-30%)
Doppler US: thigh and pelvis (+ve in 60%) Continue LMWH until INR >2 (at least 5d)
CTPA + venous phase of legs and pelvis Target INR = 2-3
85-95% sensitivity Duration
V/Q scan no longer used Remedial cause: 3mo
No identifiable cause: 6mo
Dx On-going cause: indefinite
1. Assess probability using Wells Score VC filter if repeat DVT/PE despite anticoagulation
2. Low-probability perform D-dimers
Negative excludes PE
Positive CTPA
3. High probability CTPA
NB. ve D-dimer has 95% NPV for PE
Prevention
Risk assessment for all pts
TEDS
Prophylactic LMWH
Avoid OCP/HRT if @ risk

Pneumothorax
Definition Mx
c 2O lung
Accumulation of air in the pleural space
collapse.
Tension PTX
Resuscitate pt.
Classification No CXR
Closed: intact chest wall and air leaks from lung into Large bore Venflon into 2nd ICS, mid-clavicular line
pleural cavity.
Insert ICD
Open: defect in the chest wall allows communication
between PTX and exterior: may be sucking.
Tension: air enters pleural cavity through one-way valve Traumatic
and cannot escape mediastinal compression. Resuscitate pt.
Analgesia: e.g. morphine
Causes 3-sided wet dressing if sucking
Spontaneous Insert ICD
1O: no underlying lung disease
Young, thin men (ruptured subpleural bulla)
Smokers
1O PTX
2O: underlying lung disease
COPD No
SOB and/or rim 2cm? Consider d/c
Marfans, Ehlers Danlos
Pulmonary fibrosis, sarcoidosis Yes
Yes
Trauma Aspiration successful?

Penetrating
Blunt rib #s No
Iatrogenic Insert ICD

Subclavian CVP line insertion
Positive pressure ventilation
Transbronchial biospy 2O PTX
Liver biopsy Yes
SOB and > 50yrs and Insert ICD
rim 2cm?
Presentation
No No
Symptoms
Sudden onset Aspiration successful?
Dyspnoea
Pleuritic chest pain Yes
Tension: respiratory distress, cardiac arrest
Admit for 24h
Signs
Chest
expansion
Resonant percussion
breath sounds
VR
Tension: JVP, mediastinal shift, HR, BP
Crepitus: surgical emphysema
Ix
ABG
US
CXR (expiratory film may be helpful)
Translucency + collapse (2cm rim = 50% vol loss)
Mediastinal shift (away from PTX)
Surgical emphysema
Cause: rib #s, pulmonary disease (e.g. bullae)

Pleural Effusion
Classification Ix
Effusion protein < 25g/L = transudate Blood: FBC, U+E, LFT, TFT, Ca, ESR
Effusion protein >35g/L = exudate CXR
Between 25-35g/L: apply Lights Criteria Blunt costophrenic angles
Dense shadow c meniscus
Lights Criteria Mediastinal shift away
An exudate has one of: Cause: coin lesion, cardiomegaly
Effusion : serum protein ratio >0.5 US: facilitates tapping
Effusion : serum LDH ratio >0.6 Volumetric CT
Effusion LDH is 0.6 x ULN
Diagnostic Tap
Percuss upper boarder and go 1-2 spaces below
Causes Infiltrate down to pleura
c lignocaine.
Aspirate c 21G needle
Exudates: capillary permeability Send for
Infection: pneumonia, TB Chemistry: protein, LDH, pH, glucose, amylase
Neoplasm: bronchial, lymphoma, mesothelioma Bacteriology: MCS, auramine stain, TB culture
Inflammation: RA, SLE Cytology
Infarction Immunology: SF, ANA, complement
Empyema, Ca, TB, RA and SLE

Transudates: capillary hydrostatic or oncotic pressure protein
CCF glucose <3.3mM
Renal failure pH <7.2
albumin: nephrosis, liver failure, enteropathy LDH > 0.6 x serum / ULN
Hypothyroidism
Meigs Syndrome Oesophageal Rupture
Right pleural effusion pH <7.2
Ascites amylase (also in pancreatitis)
Ovarian fibroma
Pleural Biopsy
If pleural fluid is inconclusive
Presentation CT-guided c Abrams needle
Symptoms
Asymptomatic Mx
Dyspnoea
Rx underlying cause
Pleuritic chest pain
May use drainage if symptomatic (2L/24h)
Repeated aspiration or ICD
Signs
Chemical pleurodesis if recurrent malignant effusion
Chest
Persistent effusions may require surgery
Tracheal deviation away from effusion
expansion
Stony dull percussion
air entry
Bronchial breathing just above effusion
VR
Associated disease
Ca: cachexia, clubbing, HPOA, LNs, radiation
burn, radiation tattoo
Chronic liver disease
Cardiac failure
RA, SLE
Hypothyroidism

Sarcoidosis
Definition Ix
Multisystem granulomatous disorder of unknown cause
Bloods
Epidemiology ESR
Age: 20-40yrs Ca
Sex: F>M Lymphopenia
Geo: Afro Caribbean se ACE
HLA-DRB1 and DQB1 alleles Ig
LFTs
Clinical Features: GRAULOMAS CXR, CT, MRI
In 20-40% the disease presents incidentally on CXR
Acute sarcoidosis: EN, fever, polyarthralgia, BHL Tuberculin skin test
Negative in 2/3
General
Fever Lung function tests
Anorexia and wt. Restrictive pattern
c FVC
Fatigue transfer factor
Lymphadenopathy and HSM
Tissue Biopsy
Respiratory Lung, LNs, skin nodules, liver
Upper: otitis, sinusitis Diagnostic: non-caseating granulomas
Lower (seen in 90%)
Dry cough, SOB, chest pain, lung function Ophthalmology assessment
Stage 1: BHL
Stage 2: BHL + peripheral infiltrates
Stage 3: Peripheral infiltrates alone
Stage 4: Progressive mid-zone fibrosis
c bullae
Rx
Pts.
c asymptomatic BHL do not require Rx.
Arthralgia Acute sarcoidosis
Polyarthralgia Usually resolves spontaneously
Bed rest and NSAIDs
Dactylitis
Chronic sarcoidosis
Neurological Steroids: pred 40mg/d for 4-6wks
Additional immunosuppression: methotrexate,
Peripheral and cranial polyneuropathy (esp. Bells palsy)
ciclosporin, cyclophosphamide
Meningitis, transverse myelitis, SOL
Urine
Ca Renal stones, nephrocalcinosis, DI
Prognosis
Low Hormones 60%
c thoracic sarcoidosis resolve over 2yrs
Pituitary dysfunction: e.g. amenorrhoea 20% respond to steroids
20% no improvement despite Rx
Ophthalmological
Uveitis
Keratoconjunctivitis BHL Differential
Sicca / Mikulicz / Sjogrens syndrome Sarcoidosis
Infection: TB, mycoplasma
Myocardial Malignancy: lymphoma, carcinoma
O
Restrictive cardiomyopathy 2 to granulomas + fibrosis Interstitial disease: EAA, silicosis
Pericardial effusion
Abdominal Granulomatous Disease Differential

Hepatomegaly + cholestatic LFTs Infections: TB, leprosy, syphilis, crypto, schisto
Splenomegaly AI: PBC
Vasculitis: GCA, PAN, Wegeners, Takayasus
Skin Idiopathic: Crohns, Sarcoid
EN: painful erythematous nodules on shins (paniculitis) Interstitial lung: EAA, silicosis
Lupus pernio: raised, dusky purple plaque on nose,
cheek, fingers

Interstitial Lung Disease
Principal Features Cause by Location
Dyspnoea
Dry cough Upper Zone: A PENT
Abnormal CXR / CT Aspergillosis : ABPA
Restrictive Spirometry Pneumoconiosis: Coal, Silica
Extrinsic allergic alveolitis
Negative, sero-arthropathy
Causes TB
Known Cause Lower Zone: STAIR

Environmental: asbestosis, silicosis Sarcoidosis (mid zone)
Drugs: BANS ME Toxins: BANS ME
Bleomycin, Busulfan Asbestosis
Amiodarone Idiopathic pulmonary fibrosis
Nitrofurantoin Rheum: RA, SLE, Scleroderma, Sjogrens, PM/DM
Sulfasalazine
MEthotrexate, MEthysergide
Hypersensitivity: EAA
Infection: TB, viral, fungi
Assoc. c
systemic disease
Sarcoidosis
RA
SLE, systemic sclerosis, Sjogrens, MCTD
UC, ankylosing spondylitis
Idiopathic
Idiopathic pulmonary fibrosis (CFA)

Extrinsic Allergic Alveolitis Idiopathic Pulmonary Fibrosis (CFA)
Acute allergen exposure in sensitised pts. T3HS
Chronic exposure granuloma formation and Epidemiology
obliterative bronchiolitis (T4HS) Commonest cause of interstitial lung disease
Middle age
Causes M>F = 2:1
Bird fanciers lung: proteins in bird droppings Assoc.
c other AI disease in 30%
Farmers / mushroom workers
Malt workers lung: Aspergillus clavatus Presentation
Clinical Features Symptoms

Dry cough
4-6h post-exposure Dyspnoea
Fever, rigors, malaise Malaise, wt. loss
Dry cough, dyspnoea Arthralgia
Crackles (no wheeze) OSA
Chronic Signs
Increasing dyspnoea Cyanosis
Wt. loss Clubbing
T1 respiratory failure Crackles: fine, end-inspiratory
Cor pulmonale
Complications
Ix risk Ca lung
Bloods Type 2 respiratory failure and cor pulmonale
Acute: neutrophilia, ESR
+ve se precipitins Ix
CXR
Upper zone reticulonodular opacification or Bloods
fibrosis honeycomb lung CRP
BHL (rare) Ig
Spirometry ANA+ (30%)
Restrictive defect RF+ (10%)
transfer factor during acute attacks ABG: PaO2, PaCO2
BAL
lymphocytes and mast cells CXR
lung volume
Mx Bilat lower zone retic-nod shadowing
Avoid exposure Honeycomb lung
Steroids: acute / long-term
Compensation may be payable HRCT
Shows similar changes to CXR
More sensitive
Industrial Lung Disease Spiro

Restrictive defect
transfer factor
Coal-workers Pneumoconiosis
CWP Progressive Massive Fibrosis Other
Presents as progressive dyspnoea and chronic Lung biopsy: Usual interstitial pneumonia
bronchitis BAL: may indicate disease activity
CXR: upper zone fibrotic masses lymphocytes: good prognosis
PMN or eosinophils: bad prognosis
Silicosis DTPA scan: may reflect disease activity
Quarrying, sand-blasting
Upper zone reticular shadowing and egg shell Mx
calcification of hilar nodes PMF Supportive care
Stop smoking
Asbestosis Pulmonary rehabilitation
Demolition and ship building O2 therapy
Basal fibrosis, pleural plaques Palliation
risk of mesothelioma Rx symptoms of heart failure
Chest pain, wt. loss, clubbing, recurrent effusions, Lung Tx offers only cure
dyspnoea.
CXR: pleural effusions, thickening Prognosis
Dx by histology of pleural biopsy 50% 5yr survival
<2yr survival
Pulmonary Hypertension Cor Pulmonale
Definition Definition
PA pressure >25mmHg RHF due to chronic PHT
Causes Symptoms
Dyspnoea
Left Heart Disease Fatigue
Mitral stenosis Syncope
Mitral regurgitation
Left ventricular failure
L R shunt Signs
1. JVP c prominent a wave
Lung Parenchymal Disease 2. Left parasternal heave
Mechanism 3. Loud P2 S3
Chronic hypoxia hypoxic vasoconstriction 4. Murmurs
Perivascular parenchymal changes PR: Graham Steell EDM
COPD TR: PSM
Asthma: severe, chronic 5. Pulsatile hepatomegaly
Interstitial lung disease 6. Fluid: Ascites + Peripheral oedema
CF, bronchiectasis
Pulmonary Vascular Disease Ix

Idiopathic pulmonary hypertension Bloods: FBC, U+E, LFTs, ESR, ANA, RF
Pulmonary vasculitis: scleroderma, SLE, Wegeners ABG: hypoxia hypercapnoea
Sickle cell CXR
Pulmonary embolism: acute or chronic Enlarged R atrium and ventricle
Portal HTN: portopulmonary HTN Prominent pulmonary arteries
Peripheral oligaemia
Hypoventilation ECG: P pulmonale + RVH
OSA Echo: RVH, TR, PA pressure
Morbid obesity (Pickwickian syn.) Spirometry
Thoracic cage abnormality: kyphosis, scoliosis Right heart catheterisation
Neuromuscular: MND, MG, polio
Mx
Ix Rx underlying condition
ECG pulmonary vascular resistance
P pulmonale LTOT
RVH CCB: e.g. nifedipine
RAD Sildenafil (PDE-5 inhibitor)
Echo Prostacycline analogues
Velocity of tricuspid regurgitation jet Bosentan (endothelin receptor antagonist)
Right atrial or ventricular enlargement Cardiac failure
Ventricular dysfunction ACEi + -B (caution if asthma)
Valve disease Diuretics
Right heart catheterisation: gold standard Heart-Lung Tx
Mean pulmonary artery pressure
Pulmonary vascular resistance
CO Prognosis
Vasoreactivity testing to guide Rx 50% 5ys

Obstructive Sleep Apnoea Smoking Cessation
Definition Very Brief Advice
Intermittent closure/collapse of pharyngeal airway Ask: enquire as to smoking status
apnoeic episodes during sleep. Advise: best way to stop is with support and medication
Act: provide details of where to get help
E.g. NHS stop smoking helpline
Risk Factors
Obesity
Male Facilitating Quitting
Smoker Refer to specialist stop smoking service
EtOH Nicotine replacement
Idiopathic pulmonary fibrosis Gum
Structural airway pathology: e.g. micrognathia Patches
NM disease: e.g. MND Varenicline: selective partial nicotine receptor agonist
Recommended by NICE
23% abstinence @ 1yr vs. 10% for placebo
Start while still smoking
Ix Bupropion: also an option
SpO2
Polysomnography is diagnostic
Rx
Wt. loss
Avoid smoking and EtOH
CPAP during sleep
Clinical Features
Nocturnal
Snoring
Choking, gasping, apnoeic episodes
Daytime
Morning headache
Somnolence
memory and attention
Irritability, depression
Complications
Pulmonary hypertension
Type 2 respiratory failure
Cor pulmonale
Mx
wt.
Stop smoking
CPAP @ night via a nasal mask
Surgery to relieve pharyngeal obstruction
Tonsillectomy
Uvulopalatpharyngoplasty

Endocrinology
Contents
DM: Classification, Dx and Causes ............................................................................................................................................. 60
DM: Conservative Mx .................................................................................................................................................................. 60
DM: Oral Hypoglycaemics ........................................................................................................................................................... 61
Insulin .......................................................................................................................................................................................... 61
Diabetic Complications ................................................................................................................................................................ 62
Macrovascular ............................................................................................................................................................................. 62
Diabetic Feet ............................................................................................................................................................................... 62
Diabetic Ketoacidosis .................................................................................................................................................................. 63
Hyperosmolar Non-Ketotic Coma................................................................................................................................................ 64
Hypoglycaemia ............................................................................................................................................................................ 65
Thyrotoxicosis.............................................................................................................................................................................. 66
Hypothyroidism ............................................................................................................................................................................ 67
Hyperparathyroidism ................................................................................................................................................................... 70
Hypoparathyroidism..................................................................................................................................................................... 70
Cushings Syndrome ................................................................................................................................................................... 71
Hyperaldosteronism..................................................................................................................................................................... 72
Adrenal Insufficiency ................................................................................................................................................................... 73
Phaeochromocytoma .................................................................................................................................................................. 74
Multiple Endocrine Neoplasia ...................................................................................................................................................... 74
Autoimmune Polyendocrine Syndromes ..................................................................................................................................... 74
Hypopituitarism ............................................................................................................................................................................ 75
Pituitary Tumours ........................................................................................................................................................................ 75
Hyperprolactinaemia ................................................................................................................................................................... 76
Acromegaly.................................................................................................................................................................................. 76
Diabetes Insipidus ....................................................................................................................................................................... 77
Sexual Characteristics ................................................................................................................................................................. 77

DM: Classification, Dx and Causes DM: Conservative Mx
Definition MDT
Multisystem disorder due to an absolute or relative lack of GP, endocrinologist, surgeons, specialist nurses,
endogenous insulin metabolic and vascular dieticians, chiropodists, fellow patients (education
complications. groups).
Monitoring: 4Cs
Classification
Control, glycaemic
T1DM Record of complications: DKA, HONK, hypos
Path: autoimmune destruction of -cells absolute Capillary blood glucose
insulin deficiency. Fasting: 4.5-6.5mM
Age: usually starts before puberty 2h post-prandial: 4.5-9mM
Presentation: polyuria, polydipsia, wt., DKA HbA1c
Genetics: concordance only 30% in MZs Reflects exposure over last 6-8wks
Assoc.: HLA-D3 and D4, other AI disease Aim <45 - 50mM (7.5 - 8%)
Abs: anti-islet, anti-GAD BP, lipids
T2DM Complications
Path: insulin resistance and -cell dysfunction relative Macro
insulin deficiency Pulses
Age: usually older patients BP
Presentation: polyuria, polydipsia, complications Cardiac auscultation
Genetics: concordance 80% in MZs Micro
Assoc.: obesity, exercise, calorie and EtOH excess Fundoscopy
ACR + U+Es
Sensory testing plus foot inspection
Dx
Competency
Symptomatic: Polyuria, polydipsia, wt., lethargy
With insulin injections
plasma venous glucose detected once
Checking injection sites
Fasting 7mM
BM monitoring
Random 11.1mM
Asymptomatic
Coping
venous glucose on 2 separate occasions
Psychosocial: e.g. ED, depression
Or, 2h OGTT 11.1mM
Occupation
Domestic
Glucose Testing
OGTT only needed if borderline fasting or random
Lifestyle Modification: DELAYS
glucose measurements.
Diet
Normal IFG IGT Diabetes Same as that considered healthy for everyone
Fasting <6.1 6.1 6.9 7.0 total calorie intake
75g OGTT <7.8 7.8 11 11.1 refined CHO, complex CHO
soluble fibre
fat (especially saturated)
Secondary Causes of DM Na
Avoid binge drinking
Drugs: steroids, anti-HIV, atypical neuroletics, thiazides
Pancreatic: CF, chronic pancreatitis, HH, pancreatic Ca
Exercise
Endo: Phaeo, Cushings, Acromegaly, T4
Other: glycogen storage diseases Lipids
Rx of hyperlipidaemia
O
1 prevention c statins if >40yrs (regardless of lipids)
Metabolic Syndrome
Central obesity ( waist circumference) and two of: ABP
Triglycerides Na intake and EtOH
HDL Keep BP <130/80
HTN
ACEis best (-B: mask hypos, thiazides: glucose)
Hyperglycaemia: DM, IGT, IFG
Aspirin
O
1 prevention if >50yrs or <50
c other CVD RFs
Yearly / 6 monthly check-up: 4Cs
Smoking cessation
DM: Oral Hypoglycaemics Insulin
1. Lifestyle Modification: DELAYS Principles
Ensure pt. education about
2. Start Metformin Self-adjustment c exercise and calories
(if HBA1c >target after lifestyle changes) Titrate dose
SE: nausea, diarrhoea, abdo pain, lactic acidosis Family member can abort hypo c sugary drinks
CI: GFR<30, tissue hypoxia (sepsis, MI), morning or GlucoGel
before GA and iodinated contrast media Pre-prandial BM dont tell you who much glucose is
500mg after evening meal, ing to 2g max. needed
Fasting BM before meal informs re long-acting insulin
dose.
3. Metformin + Sulfonylurea Finger-prick BM after meal informs re short-acting
(if HBA1c >target) insulin dose (for that last meal)
E.g. gliclazide MR 30mg c breakfast
SE: hypoglycaemia, wt. gain
CI: omit on morning of surgery
Common Regimes
Other Options BD Biphasic Regime

Consider adding a rapid-acting insulin BD insulin mixture 30min before breakfast and dinner
secretagogue (e.g. nateglinide) to metformin Rapid-acting: e.g. actrapid
instead of a sulfonylurea. Intermediate- / long-acting: e.g. insulatard
May be preferable if erratic lifestyle. T2 or T1 DM c regular lifestyle: children, older pts.
Consider adding pioglitazone to metformin instead Assoc, c fasting hyperglycaemia
of a sulfonylurea
Basal-Bolus Regime
Bedtime long-acting (e.g. glargine) + short acting
4. Additional Therapy before each meal (e.g. lispro)
Adjust dose according to meal size
~50% of insulin given as long-acting
1st line T1DM allowing flexible lifestyle
Add insulin insulin + metformin + sulfonylurea Best outcome
2nd line OD Long-Acting Before Bed

Add sitagliptin or pioglitazone if insulin Initial regime when switching from tablets in T2DM
unacceptable
Employment, social or recreational issues
Obesity Illness
metformin + sulfonylurea + sitagliptin / pio Insulin requirements usually (even if food intake )
Maintain calories (e.g. milk)
3rd line Check BMs 4hrly and test for ketonuria
Add exenatide (SC) if insulin unacceptable or BMI>35 insulin dose if glucose rising
metformin + sulfonylurea + exenatide
4th line
Consider acarbose if unable to use other glucose-
Side-Effects
lowering drugs Hypoglycaemia
At risk: EtOH binge, -B (mask symptoms),
elderly
Need to admit sulfonylurea-induced hypo
Lipohypertrophy
Rotate injection site: abdomen, thighs
Wt. gain in T2DM
wt. gain if insulin given
c metformin

Diabetic Complications
Summary Retinopathy, Maculopathy and Cataracts
Hyperglycaemia: DKA, HONK
Hypoglycaemia Pathogenesis
Infection Microvascular disease retinal ischaemia VEGF
Macrovascular: MI, CVA VEGF new vessel formation
Microvascular
Presentation
Retinopathy and maculopathy
Macrovascular Cataracts
MI: May be silent due to autonomic neuropathy
Rubeosis iris: new vessels on iris glaucoma
PVD: claudication, foot ulcers
CN palsies
CVA
Diabetic Retinopathy and Maculopathy
Rx: Manage CV risk factors
Commonest cause of blindness up to 60yrs
BP (aim <130/80)
Refer if pre-proliferative retinopathy / maculopathy
Smoking
Ix: fluorescein angiography
Lipids
Rx: laser photocoagulation
HBA1c
Background Retinopathy
Prevention Dots: microaneurysms
Good glycaemic control (e.g. HbA1c <6%) prevents Blot haemorrhages
both macro- and micro-vascular complications. Hard exudates: yellow lipid patches
Proved by DCCT, EDIC and UKPDS trials Pre-proliferative Retinopathy
Regular screening: fundoscopy, ACR, foot check Cotton-wool spots (retinal infarcts)
Venous beading
Diabetic Feet Haemorrhages
Proliferative Retinopathy
New vessels
Ischaemia
Pre-retinal or vitreous haemorrhage
Critical toes
Maculopathy
Absent pulses (do ABPI) acuity may be only sign
Ulcers: painful, punched-out, foot margins, pressure Hard exudates w/i one disc width of macula
points
Neuropathy Neuropathy
Loss of protective sensation
Deformity: Charcots joints, pes cavus, claw toes Pathophysiology
Injury or infection over pressure points Metabolic: glycosylation, ROS, sorbitol accumulation
Ulcers: painless, punched-out, metatarsal heads, Ischaemia: loss of vasa nervorum
calcaneum
Symmetric sensory polyneuropathy
Glove and stocking: length-dependent ( feet 1st)
Mx Loss of all modalities
Conservative Absent ankle jerks
Daily foot inspection (e.g.
c mirror) Numbness, tingling, pain (worse @ night)
Comfortable / therapeutic shoes Rx
Regular chiropody (remove callus) Paracetamol
Medical Amitriptyline, Gabapentin, SSRI
Rx infection: benpen + fluclox metronidazole Capsaicin cream
Surgical Baclofen
Abscess or deep infection
Spreading cellulitis Mononeuropathy / Mononeuritis Multiplex
Gangrene E.g. CN3/6 palsies
Suppurative arthritis
Femoral Neuropathy / Amyotrophy
Painful asymmetric weakness and wasting of quads
c
Nephropathy loss of knee jerks
Dx: nerve conduction and electromyography
Pathophysiology
Hyperglycaemia nephron loss and Autonomic Neuropathy
glomerulosclerosis
Postural hypotension Rx: fludrocortisone
Gastroparesis early satiety, GORD, bloating
Features
Diarrhoea: Rx c codeine phosphate
Microalbuminuria: urine albumin:Cr (ACR) 30mg/mM
If present ACEi / ARA Urinary retention
Refer if UCR >70 ED

Diabetic Ketoacidosis
Pathogenesis Management
Ketogenesis
insulin stress hormones and glucagon Fluids
glucose utilisation + fat -oxidation 0.9% NS infusion via large bore cannula
fatty acids ATP + generation of ketone bodies. SBP<90 1L stat + more until SBP >90
SBP>90 1L over 1h
Dehydration Then: 1L over next 2h, 1L/2h, 1L/4h, 1L/4h, 1L/6h
insulin glucose utilisation + gluconeogenesis Switch to 10% dex 1L/8h when glucose <14mM
severe hyperglycaemia
osmotic diuresis dehydration Start Potassium Replacement in 2nd Bag of Fluids
Also, ketones vomiting >5.5mM Nil
3.5-5.5mM 40mmol/L
Acidosis <3.5mM consult senior for review
Dehydration renal perfusion
Hyperkalaemia
Insulin Infusion
Precipitants Actrapid 0.1u/kg/h IVI (6u if no wt., max 15u)
Infection / stress stopping insulin
New T1DM
Presentation Assessment
Abdo pain + vomiting Hx + full examination
Gradual drowsiness Investigations: capillary, urine, blood, imaging
Sighing Kussmaul hyperventilation
Dehydration
Ketotic breath Additional Measures
Urinary catheter (aim: 0.5ml/kg/hr)
Dx NGT if vomiting or GCS
Acidosis (AG): pH <7.3 ( HCO3 <15mM) Thromboprophylaxis c LMWH
Hyperglycaemia: 11.1mM (or known DM) Refer to Specialist Diabetes Team
Ketonaemia: 3mM (2+ on dipstix) Find and treat precipitating factors
Ix
Urine: ketones and glucose, MCS Monitoring
Cap glucose and ketones Hrly capillary glucose and ketones
VBG: acidosis + K VBG @ 60min, 2h and then 2hrly
Bloods: U+E, FBC, glucose, cultures Plasma electrolytes 4hrly
CXR: evidence of infection
Aims
Subtleties ketones by 0.5mM/h or HCO3 by 3mM/h
Hyponatraemia is the norm plasma glucose by 3mM/h
Osmolar compensation for hyperglycaemia Maintain K in normal range
/ Na indicates severe dehydration Avoid hypoglycaemia
Avoid rapid in insulin once glucose normalised
Glucose decreases faster than ketones and
insulin is necessary to get rid of them.
Amylase is often (up to 10x) Resolution
Excretion of ketones loss of potential bicarbonate Ketones <0.3mM + venous pH>7.3 (HCO3 >18mM)
hyperchloraemic metabolic acidosis after Rx Transfer to sliding scale if not eating
Transfer to SC insulin when eating and drinking
Complications
Cerebral oedema: excess fluid administration
Commonest cause of mortality Transfer to SC Insulin
Aspiration pneumonia When biochemically resolved and eating
Hypokalaemia Start long-acting insulin the night before
Hypophosphataemia resp and skeletal muscle Give short-acting insulin before breakfast
weakness Stop IVI 30min after short acting
Thromboembolism
Mx: in HDU
Gastric aspiration Pt. Education
Rehydrate ID precipitating factors and provide action plan
Insulin infusion Provision of ketone meter c education on use.
Potassium replacement
Hyperosmolar Non-Ketotic Coma
The Patient
Usually T2DM, often new presentation
Usually older
Long hx (e.g. 1wk)
Metabolic Derangement
Marked dehydration and glucose >35mM
No acidosis (no ketogenesis)
Osmolality >340mosmol/kg
Complications
Occlusive events are common: DVT, stroke
Give LMWH
Mx
Rehydrate c 0.9% NS over 48h
May need ~9L
Wait 1h before starting insulin
It may not be needed
Start low to avoid rapid changes in osmolality
E.g. 1-3u/hr
Look for precipitant
MI
Infection
Bowel infarct

Hypoglycaemia
Hypoglycaemia: Whipples Triad Mx
Low plasma glucose 3mM
Symptoms consistent c hypoglycaemia Alert and Orientated: Oral Carb
Relief of symptoms by glucose administration Rapid acting: lucozade
Long acting: toast, sandwich
Symptoms
Drowsy / confused but swallow intact: Buccal Carb
Autonomic: 2.5-3 Neuroglycopenic: <2.5 Hypostop / Glucogel
Sweating Confusion Consider IV access
Anxiety Drowsiness
Hunger Seizures Unconscious or Concerned re Swallow: IV dextrose
Tremor Personality change 100ml 20% glucose (50ml 50% dextrose: not used)
Palpitations Focal neurology (e.g. CN3)
Deteriorating / refractory / insulin-induced / no access
Coma (<2.2)
1mg glucagon IM/SC
Wont work in drunks + short duration of effect (20min)
Fasting Hypoglycaemia Insulin release may rebound hypoglycaemia
Causes: EXPLAIN
Usually insulin or sulfonylurea Rx in a known diabetic
Exercise, missed meal, OD
Exogenous drugs
Pituitary insufficiency
Liver failure
Addisons
Islet cell tumours (insulinomas)
Immune (insulin receptor Abs: Hodgkins)
Non-pancreatic neoplasms: e.g. fibrosarcomas
Ix
72h fast
c monitoring
Sympto: Glucose, insulin, C-peptide, ketones
Dx
Hyperinsulinaemic hypoglycaemia
Drugs
C-pep: sulfonylurea
Normal C-pep: insulin
Insulinoma
insulin, no ketones
Non-pancreatic neoplasms
Insulin receptor Abs
insulin, ketones
Alcohol binge c no food
Pituitary insufficiency
Addisons
Insulinoma
Path: 95% benign -cell tumour usually seen c MEN1
Pres: fasting- / exercise-induced hypoglycaemia
Ix:
Hypoglycaemia + insulin
Exogenous insulin doesnt suppress C-pep
MRI, EUS pancreas
Rx: excision
Post-Prandial Hypoglycaemia
Dumping post-gastric bypass

Thyrotoxicosis
Definition Other Causes
The clinical effect of T4, usually from gland
hyperfunction. Toxic Multinodular Goitre = Plummers Disease
Autonomous nodule develops on background multinodular
Symptoms goitre.
Diarrhoea Elderly and iodine-deficient areas
appetite but wt. Iodine scan shows hot nodules
Sweats, heat intolerance
Toxic Adenoma
Palpitations
Solitary hot nodule producing T3/T4
Tremor
Most nodules are non-functional
Irritability
Oligomenorrhoea infertility Thyrotoxic Phase of Thyroiditis
Hashimotos
Signs de Quervains
Hands Subacute lymphocytic
Fast / irregular pulse
Warm, moist skin Drugs
Fine tremor Thyroxine
Palmer erythema Amiodarone
Face
Thin hair
Lid lag
Rx
Lid retraction
Medical
Symptomatic: -B (e.g. propranolol 40mg/6h)
Neck
Anti-thyroid: carbimazole (inhibits TPO)
Goitre or nodules
Titrate according to TFTs or block and replace
In Graves Rx for 12-18mo then withdraw
Graves Specific
~50% relapse surgery or radioiodine
Ophthalmopathy
SE: agranulocytosis
Exophthalmos
Ophthalmoplegia: esp. up-gaze palsy
Eye discomfort and grittiness Radiological: Radio-iodine
Photophobia and acuity Most become hypothyroid
Chemosis CI: pregnancy, lactation
Dermopathy: pre-tibial myxoedema
Surgical: Thyroidectomy
Thyroid acropachy
Recurrent laryngeal N. damage hoarseness
Hypoparathyroidism
Ix
Hypothyroidism
TSH, T4/T3
Abs: TSH receptor, TPO
Ca, LFTs
Isotope scan Thyroid Storm
in Graves
in thyroiditis Features
Ophthalmopathy: acuity, fields, movements temp
Agitation, confusion, coma
Graves Disease Tachycardia, AF
Acute abdomen
Epidemiology Heart failure
60% of cases of thyrotoxicosis
Prev: 0.5% Precipitants
Sex: F>>M=9:1 Recent thyroid surgery or radio-iodine
Age: 40-60yrs Infection
MI
Features Trauma
Diffuse goitre
c iodine uptake
Rx
Ophthalmopathy and dermopathy
1. Fluid resuscitation + NGT
Triggers: stress, infection, child-birth
2. Bloods: TFTs + cultures if infection suspected
3. Propranolol PO/IV
Associations
4. Digoxin may be needed
T1DM 5. Carbimazole then Lugols Iodine 4h later to inhibit thyroid
Vitiligo 6. Hydrocortisone
Addisons 7. Rx cause
Hypothyroidism
Epidemiology Ix
Incidence: 4/1000/yr TSH, T3/T4
Sex: F>>M=6:1 MCV normochromic anaemia
Age: >40yrs triglyceride + cholesterol
Hyponatraemia (SIADH)
Symptoms CK if assoc. myopathy
Lethargy Abs: TPO, TSH
Cold intolerance
appetite but wt. Rx
Constipation Levothyroxine
Menorrhagia Titrate to normalise TSH
mood Enzyme inducers thyroxine metabolism
Clinical improvement takes ~2wks
Signs Check for other AI disease: e.g. Addisons, PA
Cold hands
Bradycardic
Slow-relaxing reflexes Myxoedema Coma
Dry hair and skin
Puffy face Features
Goitre Looks hypothyroid
Myopathy, neuropathy Hypothermia
Ascites Hypoglycaemia
Myxoedema Heart failure: bradycardia and BP
SC tissue swelling in severe hypothyroidism Coma and seizures
Typically around eyes and dorsum of hand
Precipitants
Causes Radioiodine
Thyroidectomy
Primary Pituitary surgery
Atrophic thyroiditis (commonest UK) Infection, trauma, MI, stroke
Hashimotos thyroiditis
Subacute thyroiditis (e.g. post-partum) Mx
Post De Quervains thyroiditis Bloods: TFTs, FBC, U+E, glucose, cortisol
Iodine deficiency (commonest worldwide) Correct any hypoglycaemia
Drugs: carbimazole, amiodarone, lithium T3/T4 IV slowly (may ppt. myocardial ischaemia)
Congenital: thyroid agenesis Hydrocortisone 100mg IV
Rx hypothermia and heart failure
Post-surgical
Thyroidectomy
Radioiodine
Secondary
Hypopituitarism (v. rare cause)
Atrophic Thyroiditis
Thyroid antibodies +ve: anti-TPO, anti-TSH
Lymphocytic infiltrate atrophy (no goitre)
Associations
Pernicious anaemia
Vitiligo
Endocrinopathies
Hashimotos Thyoiditis
TPO +ve
Atrophy + regeneration goitre
May go through initial thyrotoxicosis phase
May be euthyroid or hypothyoid

Benign Thyroid Disease
Disease Clinical Features Cause Management
Simple goitre Diffuse painless goitre Endemic Thyroxine
Mass effects: - iodine deficiency
- dysphagia Total or subtotal
- stridor Sporadic thyroidectomy if pressure
- SVC obstruction - autoimmune symptoms.
- goitrogens (e.g. sulphonylureas)
Usually euthyroid, may hypothyroid - hereditary (dyshormogenic)
Multinodular Evolves from long-standing simple As for simple goitre Thyroxine
goitre goitre.
Mass effects.
Euthyroid (or subclinical hyperthyroid) Total or subtotal
thyroidectomy if pressure
symptoms.
Plummers Multinodular goitre Autonomous nodule develops on Anti-thyroid drugs
Toxic multinodular Thyrotoxicosis background multinodular goitre
goitre Uneven iodine uptake with hot nodule Total or subtotal
thyroidectomy.
Graves Diffuse goitre
c bruit Autoimmune (T2 hypersensitivity) Propranolol
Ophthalmopathy - anti-TSH Carbimazole
Dermopathy Radioiodine
Thyrotoxicosis Thyroidectomy
Assoc. c other AI disease (T1DM, PA)
uptake on radionucleotide scan
Hashimotos Diffuse painless goitre Autoimmune (T2 and T4) Levothyroxine
thyroiditis May have transient thyrotoxicosis, then - anti-TPO, -Tg
hypothyroidism
Assoc. c other AI disease (T1DM, PA)
de Quervains Diffuse painful goitre Viral: Coxsackie common Self-limiting
Preceding viral URTI common
Thyrotoxicosis hypoeu Autoimmune
iodine uptake
Subacute Diffuse painless goitre Autoimmune Self-limiting
lymphocytic May occur post-partum
Thyrotoxicosis hypoeu
Riedels thyoiditis Hard fixed thyroid mass Autoimmune fibrosis Conservative
Mass effects
Assoc. c retroperitoneal fibrosis
Follicular Single thyroid nodule Hemithyroidectomy
adenoma thyrotoxicosis (majority are cold)
May get pressure symptoms
Thyroid cysts Solitary thyroid nodule Aspiration or excision
Asympto or pressure symptoms
Can localised pain due to cyst bleed

Malignant Thyroid Disease
Disease Frequency Age Cell Origin Spread Mx
Papillary 80% 20-40 Follicular cells Nodes and lung Total thyroidectomy
- JDG node = node excision
Assoc. c Tg tumour marker lateral aberrant radioiodine
irradiation thyroid T4 to suppress TSH
>95% 10ys
Follicular 10% 40-60 Follicular cells Blood bone Total thyroidectomy +
F>M = 3:1 and lungs T4 suppression +
Tg tumour marker Radioiodine
>95% 10ys
Medullary 5% Men: young Parafollicular C-cells Do phaeo screen pre-op
30% are familial Sporadic: 40-50 Thyroidectomy +
- e.g. MEN2 CEA and calcitonin Node clearance
markers Consider radiotherapy
Anaplastic Rare >60 Undifferentiated Rapid growth Usually palliative
F>M = 3:1 follicular cells
Aggressive: local, May try thyroidectomy +
LN and blood. radiotherapy
<1% 10ys
Lymphoma 5% Lymphocytes Chemo-radiotherapy
- MALToma in Hashis
Presentation: Complications of Thyroid Surgery

Non-functional (cold)
Painless neck mass Early
Cervical mets Reactionary haemorrhage haematoma (<1%)
Compression symptoms Can airway obstruction.
Dysphagia Call anaesthetist and remove wound clips
Stridor Evacuate haematoma and re-explore wound
SVC obstruction Laryngeal oedema
Damage during intubation or surgical
Risk factors for malignancy in thyroid nodules manipulation
Solitary Can airway obstruction
Solid Recurrent laryngeal nerve palsy (0.5%)
Younger Right RLN more common (oblique ascent)
Damage to one hoarse voice
Male
Damage to both obstruction needing
Cold
trachyostomy
Risk factor: e.g. radiation exposure
Hypoparathyroidism (2.5%)
2+
Ca Chvosteks and Trousseaus
Thyroid storm
Thyroid Surgery Severe hyperthyroidism
Rx: propranolol, antithyroid drugs, Lugols iodine
Indications and hydrocortisone sodium succinate
Pressure symptoms
Relapse hyperthyroidism (>1 failed drug Rx) Late
Cosmesis Hypothyroidism
Carcinoma Recurrent hyperthyroidism
Keloid scar
Practicalities
Render euthyroid pre-op c antithyroid drugs
Stop 10 days prior to surgery (they vascularity)
Alternatively just give propronalol
Check for phaeo pre-op in medullary carcinoma
Laryngoscopy: check vocal cords pre- and post-op
Procedure
Collar incision

Hyperparathyroidism Hypoparathyroidism
PTH due to gland failure
Physiology
PTH secreted in response to Ca2+ Presentation: Ca SPASMODIC
osteoclast activity Spasms (carpopedal = Trousseaus sign)
Ca2+ and PO4 reabsorption in kidney Perioral paraesthesia
1-hydroxylation of 25OH-Vit D3 Anxious, irritable
Seizures
Presentation: Ca2+ Muscle tone colic, wheeze, dysphagia
Stones Orientation impaired (confusion)
Renal stones Dermatitis
Polyuria and polydipsia (nephrogenic DI) Impetigo herpetiformis (Ca + pustules in pregnancy)
Nephrocalcinosis Chovsteks, cardiomyopathy ( QTc TdP)
Bones
Bone pain Causes
Pathological #s Autoimmune
Moans: depression Congenital: DiGeorge
Groans Cardiac abnormality: Fallots
Abdo pain Abnormal facies
n/v and constipation Thymic aplasia
Pancreatitis Cleft palate
PUD (gastrin secretion) Hypocalcaemia
Other: Chr 22
2+
BP (check Ca in all with HTN) Iatrogenic
Surgery
Primary Hyperparathyroidism Radiation
Causes Ix
Solitary adenoma: 80% Ca, PO4, PTH, normal ALP
Hyperplasia: 20%
Pathyroid Ca: <0.5% Rx
Ca supplements
Ix Calcitriol
Ca2+ + or inappropriately normal PTH, ALP, PO4
ECG: QTc bradycardia 1st degree block Pseudohypoparathyroidism
X-ray: osteitis fibrosa cystica phalangeal erosions
Failure of target organ response to PTH
DEXA: osteoporosis Symptoms of hypocalcaemia
Short 4th and 5th metacarpals, short stature
Rx Ix: Ca, PTH
General Rx: Ca + calcitriol
fluid intake
Avoid dietary Ca2+ and thiazides ( serum Ca)
Pseudopseudohypoparathyroidism
Surgical: excision of adenoma
Normal (maternal) receptor in kidney normal
Hypoparathyroidism
biochem
Recurrent laryngeal N. palsy
Abnormal (paternal) receptors in body
pseudohypoparathyroidsm phenotype
Secondary Hyperparathyroidism
Causes
Vitamin D deficiency
Chronic renal failure
Ix
PTH, Ca, PO4, ALP, vit D
Rx
Correct causes
Phosphate binders
With Ca: calcichew
W/o Ca: sevelamer, lanthanum
Vit D: calcitriol (active), cholecalciferol (innactive)
Cinacalcet: parathyroid Ca-sensitivity
Tertiary Hyperparathyroidism
Prolonged 2O HPT autonomous PTH secretion
Ca2+, PTH, PO4, ALP
Cushings Syndrome
Definition ACTH-Independent
Clinical state produced by chronic glucocorticoid excess ACTH due to ve FB
No suppression
c any dose of dex
Causes
Features
Iatrogenic steroids: commonest cause
Adrenal adenoma / Ca: carcinoma often virilisation
Catabolic Effects
Proximal myopathy Adrenal nodular hyperplasia
Carney complex: LAME Syndrome
Striae
McCune-Albright
Bruising
Osteoporosis
Glucocorticoid Effects ACTH-Dependent

DM ACTH
Obesity
Causes
Mineralocorticoid Effects Cushings disease
HTN Bilat adrenal hyperplasia from ACTH-secreting
Hypokalaemia pituitary tumour (basophilic microadenoma)
Cortisol suppression
c high-dose dex
Ectopic-ACTH
SCLC
Appearance Carcinoid tumour
Moon face Skin pigmentation, metabolic alkalosis, wt. loss,
Acne and hirsutism hyperglycaemia
Interscapular and supraclavicular fat pads No suppression c any dose of dex
Centripetal obesity
Striae
Thin limbs Ix
Bruising 1st: 24h urinary free cortisol
Thin skin Late night serum or salivary cortisol
Highest @ AM, lowest @ midnight
Dexamethasone suppression tests
ACTH (but ACTH degrades v. quick after venepuncture)
Localisation: CT, MRI
DEXA scan
Rx: Treat Causes

Cushings disease: trans-sphenoidal excision
Adrenal adenoma / Ca: adrenelectomy
Ectopic ACTH: tumour excision, metyrapone (inhibits
cortisol synthesis)
Nelsons Syndrome
Rapid enlargement of a pituitary adenoma following
bilateral adrenelectomy for Cushings syndrome
Not typically performed nowadays
Presentation
Mass effects: bitemporal hemianopia
Hyperpigmentation

Hyperaldosteronism
Primary Hyperaldosteronism Secondary Hyperaldosteronism
Excess aldosterone, independent of RAS Due to renin from renal perfusion
Features Causes
Hypokalaemia: weakness, hypotonia, hyporeflexia, RAS
cramps Diuretics
Paraesthesia CCF
BP Hepatic failure
Nephrotic syndrome
Causes
Bilateral adrenal hyperplasia (70%) Ix
Adrenocortical adenoma (30%): Conns syndrome Aldosterone:renin ratio: normal
Ix Bartters Syndrome
U+E: / Na, K, alkalosis Autosommal recesive
Care c diuretics, hypotensives, laxatives, steroids Blockage of NaCl reabsorption in loop of Henle (as if
Aldosterone:renin ratio: c primary taking frusemide)
ECG: flat / inverted T waves, U waves, depressed ST Congenital salt wasting RAS activation
segments, prolonged PR and QT intervals hypokalaemia and metabolic alkalosis
Adrenal CT/MRI Normal BP
Rx
Conns: laparoscopic adrenelectomy
Hyperplasia: spironolactone, eplerenone or amiloride

Adrenal Insufficiency
Primary Adrenal Insufficiency: Addisons Addisonian Crisis
Destruction of adrenal cortex glucocorticoid and
mineralocorticoid deficiency Presentation
Shocked: HR, postural drop, oliguria, confused
Causes Hypoglycaemia
Autoimmune destruction: 80% in the UK Usually known Addisonian or chronic steroid user
TB: commonest worldwide
Metastasis: lung, breast, kidneys Precipitants
Haemorrhage: Waterhouse-Friedrichson Infection
Congenital: CAH Trauma
Surgery
Symptoms Stopping long-term steroids
Wt. loss + anorexia
n/v, abdo pain, diarrhoea/constipation Mx
Lethargy, depression Bloods: cortisol, ACTH, U+E, cultures
Hyperpigmentation: buccal mucosa, palmer creases Check CBG: glucose may be needed
Postural hypotension dizziness, faints Hydrocortisone 100mg IV 6hrly
Hypoglycaemia IV crystalloid
Vitiligo Septic screen
Addisonian crisis Treat underlying cause
Ix
Bloods
Na/K
glucose
Ca
Anaemia
Differential
Short synACTHen test
Cortisol before and after tetracosactide
Exclude Addisons if cortisol
9am ACTH (usually low)
Other
21-hydroxylase Abs: +ve in 80% of AI disease
Plasma renin and aldosterone
CXR: evidence of TB
AXR: adrenal calcification
Rx
Replace
Hydrocortisone
Fludrocortisone
Advice
Dont stop steroids suddenly
steroids during intercurrent illness, injury
Wear a medic-alert bracelet
F/up
Watch for autoimmune disease
Secondary Adrenal Insufficiency

i.e. hypothalamo or pituitary failure
Causes
Chronic steroid use suppression of HPA axis
Pituitary apoplexy / Sheehans
Pituitary microadenoma
Features
Normal mineralocorticoid production
No pigmentation (ACTH )

Phaeochromocytoma Multiple Endocrine Neoplasia
Pathology Definition
Catecholamine-producing tumours arising from Functioning hormone tumours in multiple organs
sympathetic paraganglia All autosomal dominant
Usually found in adrenal medulla
Extra-adrenal phaeos found by aortic bifurcation MEN1
Pituitary adenoma: prolactin or GH
Rule of 10s Parathyroid adenoma / hyperplasia
10% malignant Pancreatic tumours: gastrinoma or insulinoma
10% extra-adrenal
10% bilateral
10% part of hereditary syndromes MEN2
Thyroid medullary carcinoma
Associations Adrenal phaeochromocytoma
10% part of herediatary syndromes A) Hyperthyroidism
MEN2a and 2b B) Marfanoid habitus
Neurofibrimatosis
Von Hippel-Lindau: RCC + cerebellar signs
Carney Complex / LAME Syndrome
Presentation Lentigenes: spotty skin pigmentation
Triad: episodic headache, sweating and tachycardia Differential: Peutz-Jehgers
Other adrenergic features Atrial Myxoma
BP, palpitations Endocrine tumours: pituitary, adrenal hyperplasia
Headache, tremor, dizziness Schwannomas
Anxiety
d/v, abdo pain Peutz-Jeghers
Heat intolerance, flushes Mucocutaneous freckles on lips, oral mucosa and palms /
May have precipitant soles
Straining, abdo palpation GI hamartomas: obstruction, bleeds
Exercise, stress Pancreatic endocrine tumours
-B, IV contrast, TCAs, GA risk of cancer: CRC, pancreas, liver, lungs, breast
Ix
Plasma + urine metadrenaline
Von Hippel-Lindau
Also vanillylmandelic acid Renal cysts
Abdo CT/MRI Bilateral renal cell carcinoma
MIBG (mete-iodobenzylguanidine) scan Haemangioblastomas
Often in cerebellum cerebellar signs
Phaeochromocytoma
Rx
Pancreatic endocrine tumours
Medical
If malignant Neurofibrimatosis
Chemo or radiolabelled MIGB Dermal neurofibromas
Caf-au-lait spots
Surgery: adrenelectomy Lisch nodules
-blocker first, then -blockade pre-op Axillary freckling
Avoids unopposed -adrenergic stimulation Phaeochromocytoma
Phenoxybenzamine = -blocker
Monitor BP post-op for BP
Autoimmune Polyendocrine
Hypertensive Crisis Syndromes
Features Type 1
Pallor Autosomal recessive
Pulsating headache Addisons
Feeling of impending doom Candidiasis
BP Hypoparathyroidism
ST and cardiogenic shock
Type 2: Schmidts Syndrome
Rx
Polygenic
Phentolamine 2-5mg IV (-blocker) or labetalol 50mg IV
Addisons
Repeat to safe BP (e.g. 110 diastolic)
Thyroid disease: hypothyroidism or Graves
Phenoxybenzaime 10mg/d PO when BP controlled
T1DM
Elective surgery after 4-6wks to allow full -blockade
and volume
Alasdair Scott, expansion
2012 74
Hypopituitarism Pituitary Tumours
10% of intracranial tumours
Causes
Hypothalamic Classification
Kallmanns (anosmia + GnRH deficiency)
Tumour Size
Inflam, infection, ischaemia Microadenoma: <1cm
Pituitary Stalk Macroadenoma: >1cm
Trauma
Surgery Pathology
Tumour (e.g. craniopharyngioma) Many are non-secretory
Pituitary ~50% produce PRL
Irradiation Others produce GH or ACTH
Tumour
Ischaemia: apoplexy, Sheehans
Infiltration: HH, amyloid
Features
Commonest causes of panhypopituitarism Mass Effects

Surgery Headache
Tumour Visual field defect: bitemporal hemianopia
Irradiation CN palsies: 3, 4, 5, 6 (pressure on cavernous sinus)
Diabetes insipidus
CSF rhinorrhoea
Features Hormone Effects
PRL galactorrhoea, libido, amenorrhoea, ED
Hormone Deficiency PRL GnRH LH/FSH
GH: central obesity, atherosclerosis, CO, stength GH acromegaly
LH/FSH ACTH Cushings Disease
M: libido, ED, hair
F: libido, amenorrhoea, breast atrophy
Ix
TSH: hypothyroidism
MRI
ACTH: 2O adrenal failure
Visual field tests
Cause Hormones: PRL, IGF, ACTH, cortisol, TFTs, LF/FSH
Mass effects Suppression tests
Other hormones: e.g. prolactin excess
Rx
Medical
Ix Replace hormones
Basal hormone tests Treat hormone excess
Dynamic pituitary function test
Insulin cortisol + GH Surgical: Trans-sphenoidal excision
GnRH LH/FSH Pre-op hydrocortisone
TRH T4 + PRL
Post-op dynamic pituitary tests
MRI brain
Radiotherapy: sterotactic
Rx
Hormone replacement Pituitary Apoplexy
Treat underlying cause Rapid pituitary enlargement due to bleed into a tumour
Mass effects
Headache, meningism, GCS
Bitemporal hemianopia
Cardiovascular collapse due to acute hypopituitarism
Rx: urgent hydrocortisone 100mg IV
Craniopharyngeoma
Originates from Rathkes pouch
Commonest childhood intracranial tumour
growth failure
Calcification seen on CT/MRI

Hyperprolactinaemia Acromegaly
Causes Causes
Excess pituitary production Pituitary acidophil adenoma in 99%
Pregnancy, breastfeeding Hyperplasia from GHRH secreting carcinoid tumour
Prolactinoma (PRL >5000) GH stimulates bone and soft tissue growth through IGF1
Hypothyroidism (TRH)
Disinhibition by compression of pituitary stalk Symptoms
Pituitary adenoma Acroparaesthesia
Craniopharyngioma Amenorrhoea, libido
Dopamine antagonsists (commonest cause) Headache
Antiemetics: metoclopramide Snoring
Antipsychotics: risperidone, haldol
Sweating
Arthralgia, back ache
Carpal tunnel (50%)
Symptoms
Amenorrhoea
Signs
Infertility
Galactorrhoea
Hands
libido Spade-like
ED Thenar wasting
Mass effects from prolactinoma Boggy sweaty palms (if active)
skin fold thickness
Carpal tunnel: sensation + thenar wasting
Ix
Basal PRL: >5000 = prolactinoma Face
Pregnancy test, TFTs Prominent supraorbital ridges
MRI Scalp folds: cutis verticis gyrata
Coarse face, wide nose and big ears
Prognathism: look from side
Rx Macroglossia
1st line: Cabergoline or bromocroptine Widely-spaced teeth
Da agonist Goitre
PRL secretion and tumour size
SE: nausea, postural hypotension, fibrosis (lung Other
and heart) Puffy, oily, darkened skin skin
2nd line: Trans-sphenoidal excision Proximal weakness + arthropathy
If visual or pressure symptoms dont response to
Pituitary mass effects: bitemporal hemianopia
medical Rx
Complications
Endocrine
Impaired glucose tolerance (40%)
DM (15%)
Cardiovascular
BP
LVH
Cardiomyopathy
IHD and stroke
Neoplasia
risk of CRC
Ix
IGF1
glucose, Ca, PO4
Glucose tolerance test
GH fails to suppress
c glucose in acromegaly
Visual fields and acuity
MRI brain
Rx
1st line: trans-sphenoidal excision
2nd line: somatostatin analogues octreotide
3rd line: GH antagonist pegvisomant
4th line: radiotherapy

Diabetes Insipidus Sexual Characteristics
Symptoms Hirsutism
Polyuria
Polydipsia Causes
Dehydration Familial
Hypernatraemia: lethargy, thirst, confusion, coma Idiopathic
androgens:
Ovary: PCOS
Causes Adrenals: Cushings, adrenal Ca
Drugs: steroids
Cranial
Idiopathic: 50% PCOS
Congenital: DIDMOAD / Wolfram Syndrome Features
O
Tumours 2 oligo-/amenorrhoea infertility
Obesity
Trauma
Acene, hirsutism
Vascular: haemorrhage (Sheehans syn.)
US: bilateral polycystic ovaries
Infection: meningoencephalitis
Hormones: testosterone, SHBG, LH:FSH ratio
Infiltration: sarcoidosis
Mx
Metformin
COCP
Nephrogenic
Clomifene for infertility
Congenital
Metabolic: K, Ca
Drugs: Li, demecleocycline, vaptans
Post-obstructive uropathy
Gynaecomastia
Abnormal amount of breast tissue in men
May occur in normal puberty
Ix Causes
Bloods: U+E, Ca, glucose
Cirrhosis
Urine and plasma osmolality
Hypogonadism
Exclude DI if U:P osmolality >2
Hyperthyroidism
Oestrogen- or HCG-producing tumours: e.g. testicular
Drugs: spiro, digoxin, oestrogen
Dx
Water deprivation test
c desmopressin trial
ED
Differential Organic Causes
DM Smoking
Diuretics or Lithium EtOH
Primary polydipsia DM
Endo: hypogonadism, hyperthyroidism, Prl
Neuro: MS, autonomic neuropathy, cord lesion
Rx Pelvic surgery: bladder, prostate
Penile abnormalities: Peyronies disease
Cranial
Find cause: MRI brain
Desmopressin PO
Nephrogenic
Treat cause

Gastroenterology
Contents
Diarrhoea ..................................................................................................................................................................................... 79
C. diff Diarrhoea .......................................................................................................................................................................... 79
Constipation................................................................................................................................................................................. 80
IBS ............................................................................................................................................................................................... 80
Dysphagia.................................................................................................................................................................................... 81
Dyspepsia .................................................................................................................................................................................... 82
Peptic Ulcer Disease ................................................................................................................................................................... 83
GORD .......................................................................................................................................................................................... 84
Hiatus Hernia ............................................................................................................................................................................... 84
Haematemesis Differential .......................................................................................................................................................... 85
Rectal Bleeding Differential ......................................................................................................................................................... 85
Upper GI Bleeding ....................................................................................................................................................................... 86
Jaundice ...................................................................................................................................................................................... 87
Liver Failure ................................................................................................................................................................................. 88
Cirrhosis ...................................................................................................................................................................................... 89
Portal Hypertension ..................................................................................................................................................................... 90
Alcoholism ................................................................................................................................................................................... 91
Alcoholic Hepatitis ....................................................................................................................................................................... 91
Viral Hepatitis .............................................................................................................................................................................. 92
Non-alcoholic Fatty Liver Disease (NAFLD) ............................................................................................................................... 92
Budd-Chiari Syndrome ................................................................................................................................................................ 92
Hereditary Haemochromatosis .................................................................................................................................................... 93
1-Antitrypsin Deficiency ............................................................................................................................................................. 93
Wilsons Disease ......................................................................................................................................................................... 94
Autoimmune Hepatitis ................................................................................................................................................................. 94
Primary Biliary Cirrhosis .............................................................................................................................................................. 95
Primary Sclerosing Cholangitis ................................................................................................................................................... 95
Liver Tumours.............................................................................................................................................................................. 96
Liver Transplant in CLD ............................................................................................................................................................... 96
Inflammatory Bowel Disease: Pathology and Presentation ........................................................................................................ 97
Ulcerative Colitis: Management................................................................................................................................................... 98
Crohns Disease: Management ................................................................................................................................................... 99
Coeliac Disease......................................................................................................................................................................... 100
Malabsorption ............................................................................................................................................................................ 100
Pancreatic Cancer ..................................................................................................................................................................... 101
Chronic Pancreatitis .................................................................................................................................................................. 101
Carcinoid Tumours .................................................................................................................................................................... 102
Nutritional Deficiencies .............................................................................................................................................................. 102

Diarrhoea C. diff Diarrhoea
Definitions Pathogen
Diarrhoea = stool water stool frequency Gm+ve spore-forming anaerobe
Steatorrhoea = stool fat pale, float, smelly Release enterotoxins A and B
Faecal urgency = suggests rectal pathology Spores are v. robust and can survive for >40d
Clinical Features and Causes Epidemiology

Commonest cause (25%) of Abx assoc. diarrhoea
Acute 100% of Abx assoc. pseudomembranous colitis
Suspect gastroenteritis Stool carriage in 3% of healthy adults and 15-30% of
Travel, diet, contacts? hospital pts.
Chronic Risk Factors

Diarrhoea alternating
c constipation: IBS Abx: e.g. clindamycin, cefs, augmentin, quinolones
Anorexia, wt., nocturnal diarrhoea: organic cause age
In hospital:
c length of stay,
c C. diff +ve contact
Bloody PPIs
Vascular: ischaemic colitis
Infective: campylobacter, shigella, salmonella, E. coli, Clinical Presentations
amoeba, pseudomembranous colitis
Asymptomatic
Inflammatory: UC, Crohns
Mild diarrhoea
Neoplastic: CRC, polyps
Colitis w/o pseudomembranes
Pseudomembranous colitis
Mucus
Fulminant colitis
IBS, CRC, polyps
May occur up to 2mo after discontinuation of Abx
Pus
IBD, diverticulitis, abscess Pseudomembranous Colitis
Severe systemic symptoms: fever, dehydration
Assoc. c
medical disease Abdominal pain, bloody diarrhoea, mucus PR
T4 Pseudomembranes (yellow plaques) on flexi sig
Autonomic neuropathy (e.g. DM) Complications
Carcinoid Paralytic ileus
Toxic dilatation perforation
Assoc. c
drugs Multi-organ failure
Abx
PPI, cimetidine Ix
NSAIDs Bloods: CRP, WCC, albumin, dehydration
Digoxin CDT ELISA
Stool culture
Ix Severe Disease: 1 of
WCC >15
Bloods Cr >50% above baseline
FBC: WCC, anaemia Temp >38.5
U+E: K+, dehydration Clinical / radiological evidence of severe colitis
ESR: IBD, Ca
CRP: IBD, infection Rx
Coeliac serology: anti-TTG or anti-endomysial Abs General
Stop causative Abx
Stool Avoid antidiarrhoeals and opiates
MCS and C. diff toxin Enteric precautions
Specific
1st line: Metronidazole 400mg TDS PO x 10-14d
2nd line: Vanc 125mg QDS PO x 10-14d
Rx
Failed metro
Treat cause
Severe: Vanc 1st (may add metro IV)
Oral or IV rehydration
to 250mg QDS if no response (max 500mg)
Codeine phosphate or loperamide after each loose Urgent colectomy may be needed if
stool
Toxic megacolon
Anti-emetic if assoc. c n/v: e.g. prochlorperazine
LDH
Abx (e.g. cipro) in infective diarrhoea systemic illness Deteriorating condition
Recurrence (15-30%)
Reinfection or residual spores
Repeat course of metro x 10-14d
Alasdair Scott, 2012
Vanc if further relapse (25%) 79
Constipation IBS
Infrequent BMs (3/wk) or passing BMs less often than Disorders of enhanced visceral perception bowel
normal or
c difficulty, straining or pain. symptoms for which no organic cause can be found.
Causes: OPENED IT Dx: ROME Criteria

Obstruction Abdo discomfort / pain for 12wks which has 2 of:
Mechanical: adhesions, hernia, Ca, inflamatory Relieved by defecation
strictures, pelvic mass Change in stool frequency (D or C)
Pseudo-obstruction: post-op ileus Change in stool form: pellets, mucus
+ 2 of:
Pain Urgency
Anal fissure Incomplete evacuation
Proctalgia fugax Abdo bloating / distension
Mucous PR
Endocrine / Electrolytes Worsening symptoms after food
Endo: T4 Exclusion criteria
Electrolytes: Ca, K, uraemia >40yrs
Bloody stool
Neuro Anorexia
MS Wt. loss
Myelopathy Diarrhoea at night
Cauda equina syndrome
Ix
Elderly Bloods: FBC, ESR, LFT, coeliac serology, TSH
Diet / Dehydration Colonoscopy: if >60yrs or any features of organic
IBS disease
Toxins
Opioids Rx
Anti-mACh Exclusion diets can be tried
Bulking agents for constipation and diarrhoea (e.g.
Mx fybogel).
General Antispasmodics for colic/bloating (e.g. mebeverine)
Drink more Amitriptyline may be helpful
dietary fibre CBT
Bulking: faecal mass peristalsis

CI: obstruction and faecal impaction
Bran
Ispaghula husk (Fybogel)
Methylcellulose
Osmotic: retain fluid in the bowel

Lactulose
MgSO4 (rapid)
Stimulant: intestinal motility and secretion

CI: obstruction, acute colitis
SE: abdo cramps
Bisacodyl PO or PR
Senna
Docusate sodium
Sodium picosulphate (rapid)
Softeners
Useful when managing painful anal conditions
Liquid paraffin
Enemas
Phosphate enema (osmotic)
Suppositories
Glycerol (stimulant)

Dysphagia
Definition Achalasia
Difficulty swallowing Pathophysiology
Degeneration of myenteric plexus (Auerbachs)
Causes peristalsis
LOS fails to relax
Inflammatory Cause
Tonsillitis, pharyngitis 1O / idiopathic: commonest
2O: oesophageal Ca, Chagas disease (T. cruzii)
Oesophagitis: GORD, candida
Presentation
Oral candidiasis
Dysphagia: liquids and solids at same time
Aphthous ulcers
Regurgitation
Substernal cramps
Mechanical Block
Wt. loss
Luminal
Comps: Chronic achalasia oesophageal SCC
FB
Ix
Large food bolus
Ba swallow: dilated tapering oesophagus (Birds
Mural
beak)
Benign stricture
Manometry: failure of relaxation + peristalsis
Web (e.g. Plummer-Vinson) CXR: may show widended mediastinum
Oesophagitis OGD: exclude malignancy
Trauma (e.g. OGD) Rx:
Malignant stricture Med: CCBs, nitrates
Pharynx, oesophagus, gastric Int: endoscopic balloon dilatation, botulinum toxin
Pharyngeal pouch injection
Extra-mural Surg: Hellers cardiomyotomy (open or endo)
Lung Ca
Rolling hiatus hernia
Mediastinal LNs (e.g. lymphoma) Pharyngeal Pouch: Zenkers Diverticulum
Retrosternal goitre
Outpouching of oesophagus between upper boarder of
Thoracic aortic aneurysm
cricopharyngeus muscle and lower boarder of inferior
constrictor of pharynx
Motility Disorders
Weak area called Killians dehiscence.
Local
Defect usually occurs posteriorly but swelling usually
Achalasia
bulges to left side of neck.
Diffuse oesophageal spasm
Food debris pouch expansion oesophageal
Nutcracker oesophagus
compression dysphagia.
Bulbar / pseudobulbar palsy (CVA, MND)
Pres: regurgitation, halitosis, gurgling sounds
Systemic
Systemic sclerosis / CREST Rx: excision, endoscopic stapling
MG
Presentation Diffuse Oesophageal Spasm

Dysphagia for liquids and solids at start Intermittent dysphagia chest pain
Yes: motility disorder Ba swallow shows corkscrew oesophagus
No, solids > liquids: stricture
Difficulty making swallowing movement: bulbar palsy
Odonophagia: Ca, oesophageal ulcer, spasm Nutcracker Oesophagus
Intermittent: oesophageal spasm contraction pressure
c normal peristalsis
Constant and worsening: malignant stricture
Neck bulges or gurgles on drinking: pharyngeal pouch
Signs
Cachexia
Anaemia
Virchows node (+ve = Troisiers sign)
Neurology
Signs of systemic disease (e.g. scleroderma)
Ix
Bloods: FBC, U+E
CXR
OGD
Barium swallow video fluoroscopy
Oesophageal manometrry

Dyspepsia
Definition Eradication Therapy
Non-specific group of symptoms 7 days Rx
Epigastric pain NB. PPIs and cimetidine false ve C13 breath tests
Bloating and antigen tests stop >2wks before.
Heartburn
PAC 500
ALARM Symptoms PPI: lansoprazole 30mg BD
Anaemia Amoxicillin 1g BD
Loss of wt. Clarithromycin 500mg BD
Anorexia
PMC 250
Recent onset progressive symptoms
PPI: lansoprazole 30mg BD
Melaena or haematemesis
Metronidazole 400mg BD
Swallowing difficulty
Clarithromycin 250mg BD
Failure
Causes 95% success
Inflammation: GORD, gastritis, PUD Mostly due to poor compliance
Ca: oesophageal, gastric Add bismuth
Functional: non-ulcer dyspepsia Stools become tarry black
Mx of New Onset Dyspepsia
OGD if >55 or ALARMS
Try conservative measures for 4 wks

Stop drugs: NSAIDs, CCBs (relax LOS)
Lose wt., stop smoking, EtOH
Avoid hot drinks and spicy food
OTC
Antacids: magnesium trisilicate
Alginates: gaviscon advance
Test for H. pylori if no improvement: breath or serology

+ve eradication therapy
Consider OGD if no improvement
-ve PPI trial for 4wks
Consider OGD if no improvement
PPIs can be used intermittently to control
symptoms.
Proven GORD
Full dose PPI for 1-2mo
Then, low-dose PPI PRN
Proven PUD
Full dose PPI for 1-2mo
H. pylori eradication if positive
Endoscopy to check for resolution if GU
Then, low-dose PPI PRN

Peptic Ulcer Disease
Classification
Acute: usually due to drugs (NSAIDs, steroids) or stress
Chronic: drugs, H. pylori, Ca, Zollinger-Ellison
Features
Duodenal Ulcers Gastric Ulcers

Pathology 4x commoner cf. GU Lesser curve of gastric antrum
1st part of duodenum (cap) Beware ulcers elsewhere (often malignant)
M>F
Risk Factors H. pylori (90%) H. pylori (80%)

Drugs: NSAIDs, steroids Smoking
Smoking Drugs
EtOH Delayed gastric emptying
gastric emptying Stress
Blood group O Cushings: intracranial disease
Curlings: burns, sepsis, trauma
Presentation Epigastric pain: Epigastric pain:

Before meals and at night Worse on eating
Relieved by eating or milk Relieved by antacids
Wt. loss
Complications Surgery for PUD

Haemorrhage
Haematemeis or melaena Concepts
Fe deficiency anaemia No acid no ulcer
Perforation Secretion stimulated by gastrin and vagus N.
Peritonitis
Gastric Outflow Obstruction Vagotomy
Vomiting, colic, distension Truncal: acid secretion but prevents pyloric sphincter
Malignancy relaxation must be combined c pyloroplasty or
risk
c H. pylori gastroenterostomy.
Selective: vagus nerve only denervated where it
supplies lower oesophagus and stomach
Ix Nerves of Laterjet (supply pylorus) left intact
Bloods: FBC, urea ( in haemorrhage)
C13 breath test Antrectomy
c vagotomy
OGD (stop PPIs >2wks before) Distal half of stomach removed + anastomosis:
CLO / urease test for H. pylori Directly to duodenum: Billroth 1
Always take biopsies of ulcers to check for Ca To small bowel loop c duodenal stump oversewn:
Gastrin levels if Zollinger-Ellison suspected Billroth 2 or Polya
Subtotal gastrectomy c
Roux-en-Y
Mx Occasionally performed for Zollinger-Ellison
Conservative Complications
Lose wt. Physical
Stop smoking and EtOH Stump leakage
Avoid hot drinks and spicy food Abdominal fullness
Stop drugs: NSAIDs, steroids Reflux or bilious vomiting (improves
c time)
OTC antacids Stricture
Medical Metabolic
OTC antacids: Gaviscon, Mg trisilicate Dumping syndrome
H. pylori eradication: PAC500 or PMC250 Abdo distension, flushing, n/v
Full-dose acid suppression for 1-2mo Early: osmotic hypovolaemia
PPIs: lansoprazole 30mg OD Late: reactive hypoglycaemia
H2RAs: ranitidine 300mg nocte Blind loop syndrome malabsorption, diarrhoea
Low-dose acid suppression PRN Overgrowth of bacteria in duodenal stump
Anaemia: Fe + B12
Osteoporosis
Wt. loss: malabsorption of calories intake
GORD
Pathophysiology Rx
LOS dysfunction reflux of gastric contents
oesophagitis. Conservative
Lose wt.
Risk Factors Raise head of bed
Hiatus hernia Small regular meals 3h before bed
Smoking Stop smoking and EtOH
EtOH Avoid hot drinks and spicy food
Obesity Stop drugs: NSAIDs, steroids, CCBs, nitrates
Pregnancy
Drugs: anti-AChM, nitrates, CCB, TCAs Medical
Iatrogenic: Hellers myotomy OTC antacids: Gaviscon, Mg trisilicate
1: Full-dose PPI for 1-2mo
Symptoms Lansoprazole 30mg OD
2: No response double dose PPI BD
Oesophageal 3: No response: add an H2RA
Heartburn Ranitidine 300mg nocte
Related to meals Control: low-dose acid suppression PRN
Worse lying down / stooping
Relieved by antacids Surgical: Nissen Fundoplication
Belching Indications: all 3 of:
Acid brash, water brash Severe symptoms
Odonophagia Refractory to medical therapy
Confirmed reflux (pH monitoring)
Extra-oesophageal
Nocturnal asthma Nissen Fundoplication
Chronic cough Aim: prevent reflux, repair diaphragm
Laryngitis, sinusitis Usually laparoscopic approach
Mobilise gastric fundus and wrap around lower
Complications oesophagus
Oesophagitis: heartburn Close any diaphragmatic hiatus
Ulceration: rarely haematemesis, melaena, Fe Complications:
Gas-bloat syn.: inability to belch / vomit
Benign stricture: dysphagia
Dysphagia if wrap too tight
Barretts oesophagus
Intestinal metaplasia of squamous epithelium
Metaplasia dysplasia adenocarcinoma Hiatus Hernia
Oesophageal adenocarcinoma
Classification
Differential Dx
Oesophagitis Sliding (80%)
Infection: CMV, candida Gastro-oesophageal junction slides up into chest
IBD Often assoc.
c GORD
Caustic substances / burns
PUD Rolling (15%)
Oesophageal Ca Gastro-oesophageal junction remains in abdomen but a
bulge of stomach rolls into chest alongside the
Ix oesophagus
Isolated symptoms dont need Ix LOS remains intact so GORD uncommon
Bloods: FBC Can strangulation
CXR: hiatus hernia may be seen
OGD if: Mixed (5%)
>55yrs
Symptoms >4wks Ix
Dysphagia CXR: gas bubble and fluid level in chest
Persistent symptoms despite Rx Ba swallow: diagnostic
Wt. loss OGD: visualises the mucosa but cant exclude hernia
OGD allows grading by Los Angeles 24h pH + manometry: exclude dysmotility or achalsia
Classification
Ba swallow: hiatus hernia, dysmotility Rx
24h pH testing manometry
Lose wt.
pH <4 for >4hrs
Rx reflux
Surgery if intractable symptoms despite medical Rx.
Should repair rolling hernia (even if asympto)
as it may strangulate.
Haematemesis Differential Rectal Bleeding Differential
VINTAGE DRIPING Arse
Varices Diverticulae
Inflammation Rectal
Oesophago-gastro-duodenitis Haemorrhoids
PUD: DU is commonest cause
Infection
Neoplasia Campylobacter, shigella, E. coli, C. diff, amoebic
Oesophageal or gastric Ca dysentery
Trauma Polyps
Mallory-Weiss Tear
Mucosal tear due to vomiting Inflammation
Boerhaaves Syndrome UC, Crohns
Full-thickness tear
2cm proximal to LOS Neoplasia
Angiodysplasia + other vascular anomalies Gastic-upper bowel bleeding

Angiodysplasia
HHT Angio
Dieulafoy lesion: rupture of large arteriole in stomach or Ischaemic colitis
other bowel HHT
Angiodysplasia
Generalised bleeding diathesis
Warfarin, thrombolytics
CRF
Epistaxis

Upper GI Bleeding
Hx
Previous bleeds Management
Dyspepsia, known ulcers
Liver disease or oesophageal varices Resuscitate
Dysphagia, wt. loss Head-down.
Drugs and EtOH 100% O2, protect airway
Co-morbidities 2 x 14G cannulae + IV crystalloid infusion up to 1L.
Bloods: FBC, U+E ( urea), LFTs, clotting, x-match
o/e 6u, ABG, glucose
Signs of CLD
PR:melaena
Shock? Blood if remains shocked
Cool, clammy, CRT>2s Group specific or O- until X-matched
BP (<100) or postural hypotension (>20 drop)
urine output (<30ml/h)
Tachycardia
GCS Variceal Bleed
Terlipressin IV (splanchnic vasopressor)
Common Causes Prophylactic Abx: e.g. ciprofloxacin 1g/24h
PUD: 40% (DU commonly)
Acute erosions / gastritis:20%
Mallory-Weiss tear: 10% Maintenance
Varices: 5% Crystalloid IVI, transfuse if necessary (keep Hb10)
Oesophagitis: 5% Catheter + consider CVP (aim for >5cm H2O)
Ca Stomach / oesophagus:<3% Correct coagulopathy: vit K, FFP, platelets
Thiamine if EtOH
Rockall Score: (Prof T Rockall, St. Marys) Notify surgeons of severe bleeds
Prediction of re-bleeding and mortality
40% of re-bleeders die
Initial score pre-endoscopy
Urgent Endoscopy
Age
Haemostasis of vessel or ulcer:
Shock: BP, pulse
Adrenaline injection
Comorbidities
Thermal / laser coagulation
Final score post-endoscopy
Final Dx + evidence of recent haemorrhage Fibrin glue
Active bleeding Endoclips
Visible vessel
Variceal bleeding:
Adherent clot
2 of: banding, sclerotherapy, adrenaline,
Initial score 3 or final >6 are indications for surgery
coagulation
Balloon tamponade c Sengstaken-Blakemore tube
Oesophageal Varices Only used if exsanguinating haemorrhage or
Portal HTN dilated veins @ sites of porto-systemic failure of endoscopic therapy
anastomosis: L. gastric and inferior oesophageal veins TIPSS if bleeding cant be stopped endoscopically
30-50% c portal HTN will bleed from varices
Overall mortality 25%:
c severity of liver disease.
Causes of portal HTN After endoscopy

Pre-hepatic: portal vein thrombosis Omeprazole IV + continuation PO (s re-bleeding)
Hepatic: cirrhosis (80% in UK), schisto (commonest Keep NBM for 24h clear fluids light diet @ 48h
worldwide), sarcoidosis. Daily bloods: FBC, U+E, LFT, clotting
Post-hepatic: Budd-Chiari, RHF, constrict pericarditis H. pylori testing and eradication
Stop NSAIDs, steroids et.c.
Bleed Prevention
O
1 : -B, repeat endoscopic banding
2O: -B, repeat banding, TIPSS Indications for Surgery
Re-bleeding
Transjugular Intrahepatic Porto-Systemic Shunt (TIPSS) Bleeding despite transfusing 6u
IR creates artificial channel between hepatic vein and Uncontrollable bleeding at endoscopy
portal vein portal pressure.
Initial Rockall score 3, or final >6.
Colapinto needle creates tract through liver Open stomach, find bleeder and underrun vessel.
parenchyma which is expand using a balloon and
maintained by placement of a stent.
Used prophylactically or acutely if endoscopic therapy NB. Avoid 0.9% NS in uncompensated liver disease (worsens
fails to control variceal bleeding. ascites). Use blood or albumin for resus and 5% dex for
maintenance.
Jaundice
Physiology
Normal BR = 3-17uM
Jaundice visible @ 50uM (3 x ULN)
Hb unconjugated to BR by splenic macrophages
uBR cBR by BR-UDP-glucuronyl transferase in liver
Secreted in bile then cBR urobilinogen (colourless)
Some urobilinogen is reabsorbed, returned to liver and re-excreted into bile.
Some reabsorbed urobilinogen is excreted into the urine
The urobilinogen that remains in the GIT is converted to stercobilin (brown) and excreted.
Causes
Pre-Hepatic Hepatic Post-Hepatic
Unconjugated Conjugated
Excess BR production BR Uptake Hepatocellular Dysfunction Obstruction
Haemolytic anaemia Drugs: contrast, RMP Congen: HH, Wilsons, 1ATD Stones
Ineffective erythropoiesis CCF Infection: Hep A/B/C, CMV, EBV Ca pancreas
e.g. thalassaemia Toxin: EtOH, drugs Drugs
BR Conjugation AI: AIH PBC
Hypothyroidism Neoplasia: HCC, mets PSC
Gilberts (AD) Vasc: Budd-Chiari Biliary atresia
Crigler-Najjar (AR) Choledochal cyst
Hepatic BR Excretion Cholangio Ca
Neonatal jaundice is both Dubin-Johnson
production + conjug. Rotors
Drug-induced Jaundice Gilberts

Auto dom partial UDP-GT deficiency
Mechanism Drug 2% of the population
Haemolysis Antimalarials (e.g. dapsone) Jaundice occurs during intercurrent illness
Dx: uBR on fasting, normal LFTs
Hepatitis Paracetamol OD
RMP, INH, PZA Crigler-Najjar
Valproate Rare auto rec total UDP-GT deficiency
Statins Severe neonatal jaundice and kernicterus
Halothane Rx: liver Tx
MOAIs
Cholestasis Fluclox (may be wks after Rx)

Co-amoxiclav
OCP
Sulfonylureas
Chlopromazine, prochlorperazine
Ix
Pre-Hepatic Hepatic Post-Hepatic
Urine No BR (acholuric) BR BR
urobilinogen urobilinogen No urobilinogen
Hb if intravascular haemolysis
LFTs uBR cBR (usually) cBR
AST AST:ALT AST, ALT
LDH > 2 = EtOH ALP
< 1 = Viral GGT
GGT (EtOH, obstruction)
ALP
Function: albumin, PT
Other FBC and film FBC: anaemia Abdo US: ducts >6mm
Coombs Test Anti- SMA, LKM, SLA, ANA ERCP, MRCP
Hb electrophoresis 1AT, ferritin, caeruloplasmin Anti- AMA, ANCA, ANA
Liver biopsy

Liver Failure
Causes Mx
Cirrhosis (see below) Manage in ITU
Acute Rx underlying cause: e.g. NAC in paracetamol OD
Infection: Hep A/B, CMV, EBV, leptospirosis Good nutrition: e.g. via NGT
c high carbs
Toxin: EtOH, paracetamol, isoniazid, halothane Thiamine supplements
Vasc: Budd-Chiari Prophylactic PPIs vs. stress ulcers
Other: Wilsons, AIH
Obs: eclampsia, acute fatty liver of pregnancy Monitoring
Fluids: urinary and central venous catheters
Signs Bloods: daily FBC, U+E, LFT, INR
Jaundice Glucose: 1-4hrly + 10% dextrose IV 1L/12h
Oedema + ascites
Bruising Complications
Encephalopathy Bleeding: Vit K, platelets, FFP, blood
Aterixis Sepsis: tazocin (avoid gent: nephrotoxicity)
Constructional apraxia (5-pointed star) Ascites: fluid and salt restrict, spiro, fruse, tap, daily wt
Fetor hepaticus Hypoglycaemia: regular BMs, IV glucose if <2mM
Signs of cirrhosis / chronic liver disease Encephalopathy: avoid sedatives, lactulose enemas,
rifaximin
Ix Seizures: lorazepam
Blood Cerebral oedema: mannitol
FBC: infection, GI bleed, MCV (EtOH)
U+E Prescribing in Liver Failure
U, Cr: hepatorenal syndrome Avoid: opiates, oral hypoglycaemics, Na-containing IVI
Urea synth in liver poor test of renal function Warfarin effects
LFT Hepatotoxic drugs: paracetamol, methotrexate,
AST:ALT > 2 = EtOH isoniazid, salicylates, tetracycline
AST:ALT < 1 = Viral
Albumin: in chronic liver failure Poor Prognostic Factors
PT: in acute liver failure Grade 3/4 hepatic encephalopathy
Clotting: INR Age >40yrs
Glucose Albumin <30g/L
ABG: metabolic acidosis INR
Cause: Ferritin, 1AT, caeruloplasmin, Abs, Drug-induced liver failure
paracetamol levels
Microbiology
Hep, CMV, EBV serology Liver Transplant
Blood and urine culture
Types
Ascites MCS + SAAG
Cadaveric: heart-beating or non-heart beating
Radiology Live: right lobe
CXR
Kings College Hospital Criteria in Acute Failure
Abdo US + portal vein duplex
Paracetamol-induced Non-paracetamol
Hepatorenal Syndrome pH< 7.3 24h after ingestion PT > 100s
Renal failure in pts.
c advanced CLF Or all of: Or 3 out of 5 of:
Dx of exclusion PT > 100s Drug-induced
Cr > 300uM Age <10 or >40
Pathophysiology: Underfill theory Grade 3/4 encephalopathy >1wk from jaundice to
Cirrhosis splanchnic arterial vasodilatation encephalopathy
effective circulatory volume RAS activation renal PT > 50s
arterial vasoconstriction. BR 300uM
Persistent underfilling of renal circulation failure
Classification
Type 1: rapidly progressive deterioration (survival
<2wks)
Type 2: steady deterioration (survival ~6mo)
Rx
IV albumin + splanchnic vasoconstrictors (terlipressin)
Haemodialysis as supportive Rx
Liver Tx is Rx of choice
Cirrhosis
Causes Ix
Common Bloods
Chronic EtOH FBC: WCC and plats indicate hypersplenism
Chronic HCV (and HBV) LFTs
NAFLD / NASH INR
Other Albumin
Genetic: Wilsons, 1ATD, HH, CF
AI: AH, PBC, PSC Find Cause
Drugs: Methotrexate, amiodarone, methyldopa, EtOH: MCV, GGT
INH NASH: hyperlipidaemia, glucose
Neoplasm: HCC, mets Infection: Hep, CMV, EBV serology
Vasc: Budd-Chiari, RHF, constrict. pericarditis Genetic: Ferritin, 1AT, caeruloplasmin ( in Wilsons)
Autoimmune: Abs (there is lots of cross-over)
Signs AIH: SMA, SLA, LKM, ANA
PBC: AMA
Hands PSC: ANCA, ANA
Clubbing ( periostitis) Ig: IgG AIH, IgM PBC
Leuconychia ( albumin) Ca: -fetoprotein
Terrys nails (white proximally, red distally)
Palmer erythema Abdo US + PV Duplex
Dupuytrons contracture Small / large liver
Focal lesions
Face Reversed portal vein flow
Pallor: ACD Ascites
Xanthelasma: PBC
Parotid enlargement (esp.
c EtOH) Ascitic Tap + MCS
3
PMN >250mm indicates SBP
Trunk
Spider naevi (>5, fill from centre) Liver biopsy
Gynaecomastia
O
Loss of 2 sexual hair Mx
General
Abdo Good nutrition
Striae EtOH abstinence: baclofen helps cravings
Hepatomegaly (may be small in late disease) Colestyramine for pruritus
Splenomegaly Screening
Dilated superficial veins (Caput medusa) HCC: US and AFP
Testicular atrophy Oesophageal varices: endoscopy
Specific
Complications HCV: Interferon-
PBC: Ursodeoxycholic acid
1. Decompensation Hepatic Failure Wilsons: Penicillamine
Jaundice (conjugated)
Encephalopathy Complications
Hypoalbuminaemia oedema + ascites Varices: OGD screening + banding
Coagulopathy bruising HCC: US + AFP every 3-6mo
Hypoglycaemia
Decompensation
2. SBP Ascites: fluid and salt restrict, spiro, fruse, tap, daily wt
Coagulopathy: Vit K, platelets, FFP, blood
3. Portal Hypertension: SAVE Encephalopathy: avoid sedatives, lactulose enemas,
Splenomegaly rifaximin
Ascites Sepsis / SBP: tazocin (avoid gent: nephrotoxicity)
Varices Hepatorenal syndrome: IV albumin + terlipressin
Oesophageal varices (90% of cirrhotics)
Caput medusa Child-Pugh Grading of Cirrhosis
Worsens existing piles Predicts risk of bleeding, mortality and need for Tx
Encephalopathy Graded A-C using severity of 5 factors
Albumin
4. risk of HCC Bilirubin
Clotting
Distension: Ascites
Encephalopathy
Score >8 = significant risk of variceal bleeding
Portal Hypertension
Causes Sequelae: SAVE
Pre-hepatic: portal vein thrombosis (e.g. pancreatitis) Splenomegaly
Hepatic: cirrhosis (80% in UK), schisto (commonest Ascites
worldwide), sarcoidosis. Varices
Post-hepatic: Budd-Chiari, RHF, constrictive Encephalopathy
pericarditis, TR
Portosystemic Anastomoses Ascites

Effect Portal Systemic Pathophysiology
Oesophageal Left and short Inf. oesophageal Back-pressure fluid exudation
varices gastric veins veins effective circulating volume RAS activation
Caput medusae Peri-umbilical Superficial abdo wall (In cirrhosis: albumin plasma oncotic pressure
veins veins and aldosterone metabolism impaired)
Haemorrhoids Sup. rectal veins Inf. and mid. Rectal
(worsened veins Symptoms
Distension abdominal discomfort and anorexia
Prominent Abdominal Veins Dyspnoea
A lot more common than caput medusa venous return
Blood flow down below the umbilicus: portal HTN
Blood flow up below the umbilicus: IVC obstruction Differential: Serum Ascites Albumin Gradient (SAGG)
SAAG 1.1g/dL = Portal HTN (97% accuracy)
Encephalopathy Pre-, hepatic and post
Cirrhosis in 80%
Pathophysiology SAAG <1.1g/dL = Other Causes
hepatic metabolic function Neoplasia: peritoneal or visceral (e.g. ovarian)
Diversion of toxins from liver directly into systemic Inflammation: e.g. pancreatitis
system. Nephrotic Syndrome
Infection: TB peritonitis
Ammonia accumulates and pass to brain where
astrocytes clear it causing glutamate glutamine
Ix
glutamine osmotic imbalance cerebral oedema.
Bloods: FBC, U+E, LFTs, INR, chronic hepatitis screen
Classification US: confirm ascites, liver echogenicity, PV duplex
1: Confused irritable, mild confusion, sleep inversion Ascitic tap
2: Drowsy disorientated, slurred speech, asterixis MCS and AFB
Cytology
3: Stupor rousable, incoherence
Chemistry: albumin, LDH, glucose, protein
4: Coma unrousable, extensor plantars
SAAG = serum albumin ascites albumin
Liver biopsy
Presentation
Asterixis, ataxia
Rx
Confusion
Daily wt. aiming for 0.5kg/d reduction
Dysarthria
Fluid restrict <1.5L/d and low Na diet
Constructional apraxia
Spironolactone + frusemide (if response poor)
Seizures Therapeutic paracentesis c albumin infusion (100ml
20% albumin /L drained)
Precipitants HEPATICS
Respiratory compromise
Haemorrhage: e.g. varices
Pain / discomfort
Electrolytes: K, Na Renal impairment
Poisons: diuretics, sedatives, anaesthetics Refractory: TIPSS
Alcohol
Tumour: HCC SBP
Infection: SBP, pneumonia, UTI, HDV Pt.
c ascites and peritonitic abdomen
Constipation (commonest cause) E. coli, Klebsiella, Streps
Sugar (glucose) : e.g. low calorie diet Complicated by hepatorenal syn. in 30%
3
Ix: ascitic PMN > 250mm + MC+S
Ix
Rx: Tazocin or cefotaxime until sensitivities known
plasma NH4
Prophylaxis: high recurrence cipro long-term
Rx
Nurse 20O head up Splenomegaly
Correct any precipitants Splenic congestion
Avoid sedatives Hypersplenism: WCC, plats
Lactulose PO4 enemas to nitrogen-forming bowel
bacteria 2-4 soft stools/d
Consider rifaximin PO to kill intestinal microflora
Alcoholism Alcoholic Hepatitis
Effects Presentation
Anorexia
Hepatic D/V
Fatty liver hepatitits cirrhosis Tender hepatomegaly
AST:ALT >2, GGT Ascites
Severe: Jaundice, bleeding, encephalopathy
GIT
Gastritis, erosions Ix
PUD Bloods: MCV, GGT, AST:ALT>2
Varices Ascitic tap
Pancreatitis Abdo US + PV duplex
Carcinoma
Rx
CNS
Stop EtOH
Poor memory / cognition
Rx withdrawal
Peripheral polyneuropathy (mainly sensory)
High dose B vitamins: Pabrinex
Wernickes encephalopathy
Optimise nutrition
Confusion
Ophthalmoplegia (nystagmus, LR palsy) Daily wt., LFT, U+E, INR
Ataxia Mx complications of failure
Korsakoffs: amnesia confabulation
Fits, falls Prognosis
Maddrey score predicts mortality
Heart Mild: 0-5% 30d mortality
Arrhythmias: e.g. AF Severe: 50% 30d mortality
Dilated cardiomyopathy 1yr after admission: 40% mortality
BP
Blood
MCV
Folate deficiency anaemia
Dx: CAGE
Cut down?
Annoyed by peoples criticisms
Guilty about drinking
Eye opener?
Withdrawal
10-72h after last drink
Consider in new ward pt (3d) c acute confusion
Signs
HR, BP, tremor
Confusion, fits, hallucinations: esp formication (DTs)
Rx
Tapering regimen of chlordiazepoxide PO /
lorazepam IM
Thiamine
Mx
Group therapy or self-help (e.g. AA)
Baclofen: cravings
Acamprosate: cravings
Disulfiram: aversion therapy

Viral Hepatitis Non-alcoholic Fatty Liver Disease
(NAFLD)
Types Cryptogenic cause of hepatitis and cirrhosis assoc.
c
insulin resistance and the metabolic syndrome.
Type Spread Cause
Non-alcoholic steatohepatitis (NASH) is most extreme
A FO Seafood, especially abroad form and cirrhosis in 10%
B IV Blood, body fluids, babies (vertical)
C IV Mainly blood. Less vertical cf. HCV
Risk Factors
D IV Dependent on prior HBV infection
Obesity
E FO Developing world
HTN
T2DM
Presentation Hyperlipidaemia
Prodromal Phase
Seen particularly in HAV and BV
Presentation
Flu-like, malaise, arthralgia, nausea Mostly asymptomatic
Distaste for cigarettes in Hep A Hepatomegaly and RUQ discomfort may be present.
Icteric Phase Metabolic Syndrome

Acute jaundice in A>B>C (99, 75 and 25%) Central obesity ( waist circumference) and two of:
Triglycerides
Hepatitis
HDL
Abdo pain
HTN
Hepatomegaly
Hyperglycaemia: DM, IGT, IFG
Cholestasis: dark urine, pale stools
Extrahepatic features due to complexes (esp. Hep B)
Urticaria or vasculitic rash Ix
Cryoglobulinaemia BMI
PAN Glucose, fasting lipids
GN transaminases: AST:ALT <1
Arthritis Liver biopsy
Chronic Phase Mx
Mainly HCV and childhood HBV Lose wt.
Cirrhosis risk of HCC Control HTN, DM and lipids
Hep B
Carrier: 10%
HBsAg +ve > 6mo
Chronic hepatitis: 10%
Budd-Chiari Syndrome
Hepatic vein obstruction ischaemia and hepatocyte
Cirrhosis: 5%
damage liver failure or insidious cirrhosis.
Hep C
Carrier: 80% Causes
HCV RNA+ve >6mo Hypercoagulable states: myeloproliferative disorders
Chronic hepatitis: 80% (PV = commonest cause), PNH, anti-phospholipid, OCP
Cirrhosis: 20% Local Tumour: HCC
Congenital: membranous obstruction of IVC
Ix
FBC, LFTs, clotting Presentation
Hep A/B/C serology RUQ pain: stretching of Glissons capsule
Hepatomegaly
Rx Ascites: SAAG 1.1g/dL
Supportive Jaundice (and other features of liver failure)
No EtOH
Avoid hepatotoxic drugs (e.g. aspirin) Ix
Anti-viral Bloods: FBC, clotting, LFTs
Indicated in chronic disease US + hepatic vein Doppler
HBV: PEGinterferon Ascitic tap: protein (>2.5g/dL)
c SAAG (1.1g/dL)
HCV: PEGinterferon + ribavarin Other: JAK2 mutation analysis, RBC CD55 and CD59
Seroconversion: HBV 40%, HCV 10%
Rx
Anticoagulate unless there are varices
Ascites: fluid and salt restrict, spiro, fruse, tap, daily wt
Other options: thrombolysis, angioplasty, TIPSS
Transplant if fulminant hepatic failure or cirrhosis
Rx underlying cause
Hereditary Haemochromatosis 1-Antitrypsin Deficiency
Epidemiology Epidemiology
Prevalence: 1/3000, 10% are carriers. Prevalence: 1/4000, 10% are carriers
Age of onset: 40-60yrs (women later due to menses) Genetics: AR, Chr 14
Genetics: AR, HFE gene (High FE) on Chr6 (C282Y) Homozygotes have PiZZ phenootype
Pathophysiology Pathophysiology
Inherited, multisystem disorder resulting from abnormal 1AT is a serpin involved in control of the inflammatory
iron metabolism. cascade by inhibiting neutrophil elastase.
intestinal Fe absorption ( enterocyte DMT + 1AT is synthesised in the liver and comprises 90% of
hepatocyte hepcidin) deposition in multiple organs. se 1-globulin on electrophoresis.
Clinical Features: iron MEALS Presentation

Variable presentation
Myocardial Neonatal and childhood hepatitis
Dilated cardiomyopathy 15% of adults develop cirrhosis by 50yrs
Arrhythmias 75% of adults have emphysema (esp. smokers)
Endocrine Ix
Pancreas: DM Blood: se 1AT levels
Pituitary: hypogonadism amenorrhoea, infertility Liver biopsy: PAS+ve, diastase-resistant globules
Parathyroid: hypocalcaemia, osteoporosis CXR: emphysematous changes
Spirometry: obstructive defect
Arthritis Prenatal Dx: possible by CVS
nd rd
2 and 3 MCP joints, knees and shoulders
Liver Mx
Chronic liver disease cirrhosis HCC Mostly supportive for pulmonary and hepatic
Hepatomegaly complications.
Quit smoking
Skin Can consider 1AT therapy from pooled donors.
Slate grey discolouration
Ix
Bloods: LFT, ferritin, Fe, TIBC, glucose, genotype
X-ray: chondrocalcinosis
ECG, ECHO
Liver biopsy: Pearls stain to quantify Fe and severity
MRI: can estimate iron loading
Rx
Iron removal
Venesection: aim for Hct <0.5
Desferrioxamine is 2nd line
General
Monitor DM
Low Fe diet
Screening
Se ferritin and genotype
Screen 1st degree relatives
Transplant in cirrhosis
Prognosis
Venesection returns life expectancy to normal if non-
cirrhotic and non-diabetic.
Cirrhotic patients have >10% chance of HCC

Wilsons Disease Autoimmune Hepatitis
Epidemiology Pathophysiology
Prevalence: 3/100,000 Inflammatory disease of unknown cause characterised
Age: presents between childhood and 30 (never >56) by Abs directed vs. hepatocyte surface antigens
Genetics: AR, ATP7B gene on Chr 13 Predominantly young and middle-aged women
Classified according to Abs
T1: Adult, SMA+ (80%), ANA+ (10%), IgG
Pathophysiology T2: Young, LKM+
T3: Adult, SLA+
Mutation of Cu transporting ATPase
Impaired hepatocyte incorporation of Cu into
caeruloplasmin and excretion into bile. Presentation
Cu accumulation in liver and, later, other organs Teens and early 20s (25%)
Constitutional: fatigue, fever, malaise
Cushingoid: hirsute, acne, striae
Hepatitis
Clinical Features: CLANKAH HSM
Fever
Cornea Amenorrhoea
Kayser-Fleischer rings (70%, may need slit-lamp) Polyarthritis
Pulmonary infiltration
Liver Disease Pleurisy
Children usually present
c acute hepatitis. Post-/peri-menopausal
Fulminant necrosis may occur Present insidiously c chronic liver disease
cirrhosis
Arthritis Associated Diseases

Chondrocalcinosis Autoimmune thyroiditis
Osteoporosis DM
Pernicious anaemia
Neurology PSC
Parkinsonism: bradykinesia, tremor, chorea, tics UC
Spasticity, dysarthria, dysphagia GN
Ataxia AIHA (Coombs +ve)
Depression, dementia, psychosis
Kidney
Ix
Fanconis syn. (T2 RTA) osteomalacia
LFTs
Abortions IgG
Auto Abs: SMA, LKM, SLA, ANA
Haemolytic anaemia WCC and plats = hypersplenism
Coombs negative Liver biopsy
Ix Mx
Bloods: Cu, caeruloplasmin Immunosuppression
Prednisolone
NB. Caeruloplasmin is an acute-phase protein and may Azathioprine as steroid-sparer
be high during infection. It may also be low protein- Liver transplant (disease may recur)
deficient states: nephrotic syndrome, malabsorption
24h urinary Cu Prognosis

Liver biopsy: hepatic Cu Remission in 80% of patients
MRI: basal-ganglia degeneration 10yr survival 80%
Rx
Diet: avoid high Cu foods: liver, chocolate, nuts
Penicillamine lifelong (Cu chelator)
SE: nausea, rash, WCC, Hb, plats, lupus,
haematuria
Monitor FBC and urinary Cu excretion
Liver Tx if severe liver disease
Screen siblings

Primary Biliary Cirrhosis Primary Sclerosing Cholangitis
Epidemiology Pathophysiology
Prev: 4/100,000 Inflammation, fibrosis and strictures and intra- and
Sex: F>>M = 9:1 extra-hepatic ducts.
Age: 50s Chronic biliary obstruction 2O biliary cirrhosis liver
failure
Pathology
Intrahepatic bile duct destruction by chronic Epidemiology
granulomatous inflammation cirrhosis Age: 30-50yrs
Sex: M>F = 2:1
Presentation: PPBBCCS
Often asympto and Dx incidentally (ALP)
Presentation
May be asypmto and Dx incidentally (ALP)
Jaundice occurs late
Pruritus and fatigue
Symptoms
Pigmentation of face
Jaundice
Bones: osteoporosis, osteomalacia ( vit D)
Pruritus and fatigue
Big organs: HSM
Abdo pain
Cirrhosis and coagulopathy ( vit K)
Cholesterol : xanthelasma, xanthomata Signs
Steatorrhoea Jaundice: dark urine, pale stools
HSM
Associated Diseases Complications

Thyroid disease Bacterial cholangitis
RA, Sjogrens, scleroderma Cholangiocarcinoma
Coeliac disease CRC
RTA
Membranous GN
Associated Diseases
UC
Ix 3% of those c UC have PSC
LFTs: ALP, GGT, AST/ALT 80-100% of those c PSC have UC/Crohns
Late: BR, PT, albumin Crohns (much rarer)
Abs: AMA+ (98%) AIH
IgM HIV
cholesterol
TSH
US to exclude extra-hepatic cholestasis Ix
Liver biopsy: non-caseating granulomatous inflam LFTs: ALP initially, then BR
Abs: pANCA (80%), ANA and SMA may be +ve
ERCP/MRCP: beaded appearance of ducts
Rx Biopsy: fibrous, obliterative cholangitis
Symptomatic
Pruritus: colestyramine, naltrexone
Diarrhoea: codeine phosphate Rx
Osteoporosis: bisphosphonates No curative medical therapy: transplant needed
Specific Symptomatic
ADEK vitamins Pruritus: colestyramine, naltrexone
Ursodeoxcholic acid: LFTs but no effect on Diarrhoea: codeine phosphate
mortality or need for transplant Specific
Liver transplant ADEK vitamins
End-stage disease or intractable pruritus Ursodeoxycholic acid improves cholestasis only
Recurrence occurs in ~20% but doesnt usually Abx for cholangitis
graft failure. Endoscopic stenting for dominant strictures
Screening
Cholangiocarcinoma: US + Ca19-9
Prognosis CRC: colonoscopy
Once jaundice develops survival is <2yrs Transplant
Recurrence occurs in 30%

Liver Tumours Liver Transplant in CLD
Pathology Types
90% of liver tumours are 2O metastases Cadaveric: heart-beating or non-heart beating
1O in men: stomach, lung, colon Live: right lobe
1O in women: breast, colon, stomach, uterus
Less common: pancreas, leukaemia, lymphoma Indications
90% of primary tumours are HCC. Advanced cirrhosis
Benign tumours: haemangiomas, adenomas, cysts HCC
Symptoms Contraindications
Benign tumours are usually asymptomatic Extra-hepatic malignancy
Systemic: fever, malaise, wt. loss, anorexia Severe cardiorespiratory disease
RUQ pain: stretching of Glissons capsule Systemic sepsis
Jaundice is often late, except in cholangiocarcinoma HIV infection
May rupture intraperitoneal haemorrhage Non-compliance c drug therapy
Signs Post-op
Hepatomegaly: smooth or hard and irregular 12-24h on ITU
Signs of chronic liver disease Immunosuppression
Abdominal mass Ciclosporin / Tacrolimus +
Hepatic bruit (HCC) Azathioprine / Mycophenolate Mofetil +
Prednisolone
Ix
Bloods: LFTs, hepatitis serology, AFP Complications
Imaging: Acute rejection (T-cell mediated)
US or CT / MRI guided diagnostic biopsy 50% @ 5-10 days
ERCP + biopsy in suspected cholangiocarcinoma Pyrexia, tender hepatomegaly
Biopsy (seeding may occur along tract) or change immunosuppressants
Find primary: e.g. colonoscopy, mammography Sepsis
Hepatic artery thrombosis
Liver Mets CMV infection
c type and extent of 1O
Rx and prognosis vary Chronic rejection (6-9mo): shrinking bile ducts
Small, solitary CRC mets may be resectable Disease recurrence (e.g. HBV)
Advanced disease prognosis: < 6mo
Prognosis
HCC Depends on disease aetiology
Rare in West, common in China and sub-Saharan Africa 60-90% 5ys
Causes
Viral hepatitis
Cirrhosis: EtOH, HH, PBC
Aflatoxins (produced by Aspergillus)
Mx
Resection of solitary tumours improves prognosis (13
59%), but 50% have recurrence.
Also: chemo, percutaneous ablation and embolization
Cholangiocarcinoma
Biliary tree malignancy (10% of liver 1O tumours)
Causes
Flukes (Clonorchis)
PSC
Congenital biliary cysts
UC
Presentation
Fever, malaise
Abdominal pain, ascites, jaundice
BR, ALP
Mx
30% resectable
Palliative stenting:
Alasdair Scott, 2012 percutaneous or ERCP 96
Inflammatory Bowel Disease: Pathology and Presentation
Epidemiology Pathology
UC Crohns UC Crohns
Prev 100-200 /100,000 50-100 /100,000 Macroscopic
Age 30s 20s Location Rectum + colon Mouth to anus
Sex F>M (just) backwash ileitis esp. terminal ileum
Aet Concordance = 10% Concordance = 70% Distribution Contiguous Skip lesions
Smoking protective Smoking risk Strictures No Yes
TH2-mediated TH1/TH17-mediated
Microscopic
Inflammation Mucosal Transmural
Crypt Abscesses
Ulceration Shallow, broad Deep, thin, serpiginous
cobblestone mucosa
Fibrosis None Marked
Granulomas None Present
Pseudoplyps Marked Minimal
Fistulae No Yes
Presentation
UC Crohns
Symptoms
Systemic Fever, malaise, anorexia, wt. loss in active disease
Abdominal Diarrhoea Diarrhoea (not usually bloody)
Blood mucus PR Abdominal pain
Abdominal discomfort Wt. loss
Tenesmus, faecal urgency
Signs
Abdominal Fever Aphthous ulcers, glossitis
Tender, distended abdomen Abdominal tenderness
RIF mass
Perianal abscesses, fistulae, tags
Anal / rectal strictures
Extra-abdominal Skin Joints
Clubbing Arthritis (non-deforming, asymm)
Erythema nodosum Sacroiliitis
Pyoderma gang (esp. UC) Ank spond
HPB
Eyes PSC + cholangiocarcinoma (esp. UC)
Iritis Gallstones (esp. Crohns)
Episcleritis Fatty liver
Conjunctivitis Other
Amyloidosis
Oxalate renal stones (esp. Crohns)
Complications Toxic megacolon Fistulae

Diameter >6cm Entero-enteric/colonic diarrhoea
Risk of perforation Enterovesical frequency, UTI
Bleeding Enterovaginal
Malignancy Perianal pepperpot anus
CRC in 15% c pancolitis for 20yrs Strictures obstruction
Cholangiocarcinoma Abscesses
Strictures obstruction Abdominal
Venous thrombosis Anorectal
Malabsorption
Fat Steatorrhoea, gallstones
B12 megaloblastic anaemia
Vit D osteomalacia
Protein oedema
Toxic megacolon and Ca may occur (< cf.
UC)
Ulcerative Colitis: Management
Ix Inducing Remission in Mild / Mod Disease
Bloods: OPD-based
FBC: Hb, WCC
LFT: albumin Oral Therapy
CRP/ESR 1st line: 5-ASAs
Blood cultures 2nd line: prednisolone
Stool
MCS: exclude Campy, Shigella, Salmonella Topical Therapy: mainly left-sided disease
CDT: C. diff may complicate or mimic Proctitis: suppositories
Imaging More proximal disease: enemas or foams
AXR: megacolon (>6cm), wall thickening 5-ASAs steroids (prednisolone or budesonide)
CXR: perforation
CT Additional Therapy: steroid sparing
Ba / gastrograffin enema Azathioprine or mercaptopurine
Lead-pipe: no haustra Infliximab: steroid-dependent pts
Thumbprinting: mucosal thickening
Pseudopolyps: regenerating mucosal island Maintaining Remission
Ileocolonoscopy + regional biopsy: Baron Score 1st line: 5-ASAs PO sulfasalazine or mesalazine
Topical Rx may be used in proctitis
Severity 2nd line: Azathioprine or 6-mercaptopurine
Relapsed on ASA or are steroid-dependent
Truelove and Witts Criteria Use 6-mercaptopurine if azathioprine intolerant
3rd line: Infliximab / adalimumab
Mild Moderate Severe
Motions <4 4-6 >6
Emergency Surgery
PR bleed small moderate large
20% require surgery at some stage
Temp Apyrexic 37.1-37.8 >37.8
30%
c colitis require surgery w/i 5yrs
HR <70 70-90 >90
Hb >11 10.5-11 <10.5
Indications
ESR <30 >30
Toxic megacolon
Perforation
Massive haemorrhage
Acute Severe UC Failure to respond to medical Rx
Resus: Admit, IV hydration, NBM
Hydrocortisone: IV 100mg QDS + PR Procedures
Transfuse if required Total / subtotal colectomy c end ileostomy mucus
Thromboprophylaxis: LMWH fistula
Monitoring Followed after ~3mo by either
Bloods: FBC, ESR, CRP, U+E Completion proctectomy + Ileal-pouch anal
Vitals + stool chart anastomosis (IPAA) or end ileostomy
Twice daily examination Ileorectal anastomosis (IRA)
AXR Panproctocolectomy + permanent end ileostomy
Acute colitis op mortality: 7% (30% if perforated)
NB. RCTs show no benefit of Abx: not routinely recommended
May use: megacolon, perforation, uncertain Dx
Elective Surgery
Acute Complications
Perforation Indications
Bleeding Chronic symptoms despite medical therapy
Toxic megacolon (>6cm) Carcinoma or high-grade dysplasia
VTE
Procedures
Improvement oral therapy Panproctocolectomy c end ileostomy or IPAA
Switch to oral pred + a 5-ASA Total colectomy
c IRA
Taper pred after full remission
Surgical Complications
No Improvement rescue therapy Abdominal
On day 3: stool freq >8 or CRP >45 SBO
Predicts 85% chance of needing a colectomy during Anastomotic stricture
the admission Pelvic abscess
Discussion between pt, physician and surgeon Stoma: retraction, stenosis, prolapse, dermatitis
Medical: ciclosporin, infliximab or visilizumab (anti-T cell) Pouch
Surgical Pouchitis (50%): metronidazole + cipro
female fertility
Faecal leakage
Crohns Disease: Management
Ix Inducing Remission in Mild / Mod Disease
Bloods: (top 3 are severity markers) OPD treatment
FBC: Hb, WCC
LFT: albumin Supportive
CRP/ESR High fibre diet
Haematinics: Fe, B12, Folate Vitamin supplements
Blood cultures
Stool Oral Therapy
MCS: exclude Campy, Shigella, Salmonella 1st line
CDT: C. diff may complicate or mimic Ileocaecal: budesonide
Imaging Colitis: sulfasalazine
AXR: obstruction, sacroileitis 2nd line: prednisolone (tapering)
CXR: perforation 3rd line: methotrexate
MRI 4th line: infliximab or adalimumab
Assess pelvic disease and fistula
Assess disease severity Perianal Disease
Small bowel follow-through or enteroclysis Occurs in ~50%
Skip lesions Ix: MRI + EUA
Rose-thorn ulcers Rx
Cobblestoning: ulceration + mural oedema Oral Abx: metronidazole
String sign of Kantor: narrow terminal ileum Immunosuppression infliximab
Endoscopy Local surgery seton insertion
Ileocolonoscopy + regional biopsy: Ix of choice
Wireless capsule endoscopy Maintaining Remission
Small bowel enteroscopy 1st line: azathioprine or mercaptopurine
2nd line: methotrexate
3rd line: Infliximab / adalimumab
Severe Attack
Assessment
Surgery
temp, HR, ESR, CRP, WCC, albumin 50-80% need 1 operation in their life
Never curative
Management Should be as conservative as possible
Resus: Admit, NBM, IV hydration
Hydrocortisone: IV + PR if rectal disease Indications
Abx: metronidazole PO or IV Emergency
Failure to respond to medical Rx
Thromboprophylaxis: LMWH
Intestinal obstruction or perforation
Dietician Review
Massive haemorrhage
Elemental diet
Elective
Liquid prep of amino acids, glucose and fatty
Abscess or fistula
acids
Perianal disease
Consider parenteral nutrition
Chronic ill health
Monitoring Carcinoma
Vitals + stool chart
Daily examination Procedures
Limited resection: e.g. ileocaecal
Improvement oral therapy
Stricturoplasty
Switch to oral pred (40mg/d)
Defunction distal disease c temporary loop ileostomy
No Improvement rescue therapy
Complications
Discussion between pt, physician and surgeon
Stoma complications
Medical: methotrexate infliximab
Enterocutaneous fistulae
Surgical
Anastomotic leak or stricture
Short gut
<1-2m small bowel
Features
Steatorrhoea
ADEK and B12 malabsorption
Bile acid depletion gallstones
Hyperoxaluria renal stones
Rx
Dietician
Supplements or TPN
Loperamide
Coeliac Disease
Epidemiology Ix
Prev: 0.5 1% Bloods: FBC, LFTs (alb), INR, Vit D and bone, red cell
Age: Any, bimodal: infancy and 50-60yrs folate, serum B12
Sex: F>M Abs
Geo: in Ireland and N. Africa Anti-endomysial IgA (95% specificity)
Anti-TTG IgA
Pathophysiology Both above c exclusion diet
HLA-DQ2 (95%) and DQ8 Anti-gliadin IgG persist c exclusion diet)
CD8+ mediated response to gliadin in gluten IgA in most but may have IgA deficiency
Stools
Presentation: GLIAD Stool cysts and antibody: exclude Giardia
OGD and duodenal biopsy
GI Malabsorption: fatigue, weakness Subtotal villous atrophy
Carb Crypt hyperplasia
N/V/D Intra-epithelial lymphocytes
Abdo distension + colic
Flatus Rx
Wt. Lifelong gluten-free diet
Fat Avoid: barley, rye, oats, wheat
Steatorrhoea OK: Maize, soya, rice
Hyperoxaluria renal stones Verify diet by endomysial Ab tests
Protein Pneumovax as hyposplenic
Protein-losing enteropathy if severe Dermatitis herpetiformis: dapsone
Haematinics
Folate and Fe anaemia
Vitamins
Vit D and Ca bone pain, osteoporosis Malabsorption
Vit K petechiae and INR
B2 (riboflavin) angular stomatitis Presentation
B1 and B6 polyneuropathy Diarrhoea / Steatorrhoea
Wt. loss
Lymphoma and Carcinoma Lethargy
Enteropathy-associated T-cell lymphoma
Adenocarcinoma of small bowel Causes
Other Ca: breast, bladder, breast Common in UK: Coeliac, Chronic pancreatitis, Crohns
Rarer
Immune Associations Bile: PBC, ileal resection, colestyramine
IgA deficiency Pancreatic insufficiency: Ca, CF, chronic panc
T1DM Small bowel: resection, tropical sprue, metformin
PBC Bacterial overgrowth: spontaneous, post-op
blind loops, DM, PPIs
Anaemia Infection: Giardia, Strongyloides, Crypto parvum
or MCV Hurry: post-gastrectomy dumping
Hyposplenism: Howell-Jolly bodies, target cells
Ix
Dermatological Coeliac tests
Dermatitis herpetiformis: 15-20% Stool microscopy
Symmetrical vesicles, extensor surfaces Faecal elastase
Esp. elbows Hydrogen breath test
Very itchy MRI / CT
Responds to gluten-free diet or dapsone
ERCP (chronic pancreatitis)
Biopsy: granular deposition of IgA
Small bowel endoscopy
Aphthous ulcers

Pancreatic Cancer Chronic Pancreatitis
Risk Factors: SINED Causes: AGITS
Smoking Alcohol
Inflammation: chronic pancreatitis Genetic
Nutrition: fat diet CF
EtOH HH
DM Hereditary pancreatitis
Immune
Pathology Lymphoplasmacytic sclerosing pancreatitis (IgG4)
Mostly ductal adenocarcinoma Triglycerides
Metastasis early, present late Structural
60% head Obstruction by tumour
25% body Pancreas divisum
15% tail
Endocrine tumours are rare Presentation
Epigastric pain
Bores through to back
Presentation
Relieved by sitting back or hot water bottle
Typically male >60yrs
erythema ab igne
Head: painless obstructive jaundice Exacerbated by fatty food or EtOH
c dark urine + pale stools
Steatorrhoea
Body / Tail: epigastric pain Wt. loss
Radiates to back, relieved sitting forward DM
Anorexia and wt. loss Epigastric mass: pseudocyst
Acute pancreatitis
Sudden onset DM in the elderly
Ix
Signs glucose
faecal elastase
Epigastric mass
US: pseudocyst
Jaundice
AXR: speckled pancreatic calcifications
Palpable gallbladder
CT: pancreatic calcifications
Thrombophlebitis migrans (Trousseau Sign)
Splenomegaly: PV thrombosis portal HTN
Ascites Rx
Drugs
Analgesia: may need coeliac plexus block
Ix
Creon
Bloods: cholestatic LFTs, Ca19-9, Ca
ADEK vitamins
Imaging DM Rx
US: pancreatic mass, dilated ducts, hepatic mets,
Diet
allows biopsy
No EtOH
EUS: better than CT/MRI for staging
fat, carb
ERCP
Surgery
Shows anatomy
Ind: unremitting pain, wt. loss
Allows stenting
Pancreatectomy
Rx Complications
Surgery
Pseudocyst
Fit, no mets, tumour 3cm (10% of pts)
DM
Whipples pancreatoduodenectomy
Pancreatic Ca
Post-op chemo delays progression
5ys = 5-14% Biliary obstruction
Palliation Splenic vein thrombosis splenomegaly
Endoscopic / percutaneous stenting of CBD
Palliative bypass surgery
Pain relief: may need coeliac plexus block
Prognosis
Mean survival <6mo Whipples Procedure
5ys = <2%

Carcinoid Tumours Nutritional Deficiencies
Pathology Vitamin A Xerophthalmia
Diverse group of neuroendocrine tumours of Dry conjunctivae, develop spots (Bitots spots)
enterochromaffin cell origin capable of producing 5HT Corneas become cloudy then ulcerate
May secrete: 5-HT, VIP, gastrin, glucagon, insulin, ACTH Night blindness total blindness
Carcinoid syndrome suggest bypass of first-pass
metabolism and is strongly assoc. c metastatic disease. Thiamine (B1) Beri Beri
10% part of MEN1 Wet: heart failure + oedema
Sites Dry: polyneuropathy
Appendix: 45% Wernickes: ophthalmoplegia, ataxia, confusion
Ileum: 30%
Colorectum: 20% Niacin / Nicotinic acid (B3) Pellagra
Stomach: 10% Diarrhoea, Dermatitis, Dementia
Elsewhere in GIT and bronchus
Also: neuropathy, depression, ataxia
Consider all as malignant
Causes: dietary, isoniazid, carcinoid syndrome
Pyridoxine (B6)
Presentation Peripheral sensory neuropathy
Cause: PZA
Local
Appendicitis
Cyanocobalamin (B12)
Intussusception or obstruction
Glossitis sore tongue
Abdominal pain
Peripheral neuropathy
Paraesthesia
Carcinoid Syndrome: FIVE HT
Early loss of vibration and proprioception
Flushing: paroxysmal, upper body wheals
ataxia
Intestinal: diarrhoea
SCDC
Valve fibrosis: tricuspid regurg and pulmonary stenosis Dorsal and corticospinal tracts
whEEze: bronchoconstriction Sensory loss and UMN weakness
st
Hepatic involvement: bypassed 1 pass metabolism Overall mixed UMN and LMN signs c sensory
Tryptophan deficiency pellagra (3Ds) disturbance
Extensor plantars + absent knee and ankle
jerks
Ix
urine 5-hydroxyindoleacetic acid Vitamin C Scurvy
plasma chromogranin A Gingivitis
CT/MRI: find primary Bleeding: gums, nose, hair follicles (petechial)
Muscle pain / weakness
Oedema
Rx Corkscrew hairs
Symptoms: octreotide or loperamide
Curative Vitamin D Osteomalacia
Resection: tumours are v. yellow Bone pain
Give octreotide to avoid carcinoid crisis #s
Carcinoid Crisis Vitamin K

Tumour outgrows blood supply or is handled too factors: 2, 7, 9, 10, C and S
much massive mediator release Bruising, petechiae
Vasodilatation, hypotension, bronchoconstriction, Bleeding: e.g. epistaxis, menorrhagia
hyperglycaemia
Rx: high-dose octreotide
Prognosis
Median survival is 5-8yrs (~3yrs if mets present)

Nephrology
Contents
Renal Physiology ....................................................................................................................................................................... 104
Urine .......................................................................................................................................................................................... 105
Urea and Creatinine .................................................................................................................................................................. 105
Causes of Renal Disease .......................................................................................................................................................... 106
Presentation of Renal Failure .................................................................................................................................................... 106
Urinary Tract Infection ............................................................................................................................................................... 107
Glomerulonephritis .................................................................................................................................................................... 108
Asymptomatic Haematuria ........................................................................................................................................................ 108
Nephritic Syndrome / Acute GN ................................................................................................................................................ 109
Nephrotic Syndrome .................................................................................................................................................................. 109
Acute Kidney Injury.................................................................................................................................................................... 110
Management of Acute Renal Failure ......................................................................................................................................... 111
Interstitial Nephritidies ............................................................................................................................................................... 112
Nephrotoxins ............................................................................................................................................................................. 112
Chronic Renal Failure ................................................................................................................................................................ 113
Renal Transplant ....................................................................................................................................................................... 114
Renal Complications of Systemic Disease ................................................................................................................................ 115
Renal Vascular Disease ............................................................................................................................................................ 116
Renal Tubular Disease .............................................................................................................................................................. 116
Renal Cystic Diseases .............................................................................................................................................................. 117

Renal Physiology
The Glomerulus Diuretics
Epithelial pouch invaginated by capillary tuft
Semi-permeable filter Carbonic Anhydrase Inhibitors (acetazolamide)
Endothelium MOA: inhibit carbonic anhydrase in PCT
Basement membrane Effect: HCO3 reabsorption small Na loss
Epithelium Use: glaucoma
Mesangial cells are specialised smooth muscle cells that SE: drowsiness, renal stones, metabolic acidosis
support the glomerulus and regulate blood flow and GFR
Loop Diuretics (fursemide, bumetanide)

Filtration MOA: inhibit Na/K/2Cl symporter in thick ascending limb
Receive 25% of CO (1200ml/min) Effect: massive NaCl excretion, Ca and K excretion
20% of blood volume is filtered (~250ml/min) Use: Rx of oedema CCF, nephrotic syndrome,
GBM is vely charged retention of anionic proteins hypercalcaemia
such as albumin which are small enough to pass. SE: hypokalaemic met alkalosis, ototoxic, Hypovolaemia
Filtration is key to excretion of waste and remains
constant over a range of pressures (80-200mmHg).
Flow will depend on Na and water reabsorption. Thiazide Diuretics (bendroflumethazide)
MOA: inhibit NaCl co-transporter in DCT
Effect: moderate NaCl excretion, Ca reabsorption
Na Reabsorption Use: HTN, renal stones, mild oedema
Main factor determining extracellular volume SE: K, hyperglycaemia, urate (CI in gout)
BP and NaCl @ macula densa (DCT) renin release
aldosterone release more Na/K pumps.
K-Sparing Diuretics (spironolactone, amiloride)
MOA
Water Reabsorption Spiro: aldosterone antagonist
Determines ECF osmolality Amiloride: blocks DCT/CD luminal Na channel
osmolality or BP ADH release Effect: Na excretion, K and H excretion
Use: used c loop or thiazide diuretics to control K loss,
spiro has long-term benefits in aldosteronsim (LF, HF)
The Nephron SE: K, anti-androgenic (e.g. gynaecomastia)
PCT: Reabsorption of filtrate
70% of total Na+ reabsorption Osmotic Diuretics (mannitol)
Reabsorption of amino acids, glucose, cations
MOA: freely filtered and poorly reabsorbed
Bicarbonate reabsorbed using carbonic anhydrase
Effect: brain volume and ICP
Use: glaucoma, ICP, rhabdomyolysis
Thick Ascending Limb: Creation of osmolality gradient
SE: Na, pulmonary oedema, n/v
20% of Na reabsorption
Na/K/2Cl triple symporter
DCT: pH and Ca reabsorption

5% of Na reabsorption
Apical NaCl co-transporter
2+
Ca reabsorption under control of PTH
Medullary CD: pH and K regulation

Na reabsorption coupled to K or H excretion
Basolateral aldosterone-sensitive Na/K pump
Cortical CD: Regulation of water reabsorption

Water reabsorption controlled by aquaporin-2 channels
Endocrine Function
Secretion of renin by juxtaglomerular apparatus
EPO synthesis
1-hydroxylation of vitamin D (controlled by PTH)

Urine Urea and Creatinine
Haematuria Creatinine
Renal Creatinine is synthesised during muscle turnover.
Congenital: PCK Freely filtered and small proportion secreted by PCT
Trauma muscle creatinine: age, sex, race
Infection: pyelonephritis Plasma Cr doesnt above normal until 50% in GFR
Neoplasm
Immune: GN, TIN
Urea
Extra-renal Produced from ammonia by liver in ornithine cycle
Trauma: stones, catheter c protein meal (e.g. upper GI bleed, supplements)
Infection: cystitis, prostatitis, urethritis c hepatic impairment
Neoplasm: bladder, prostate 10-70% is reabsorbed: depends on urine flow.
Bleeding diathesis flow urea reabsorption (e.g. in dehydration)
Drugs: NSAIDs, frusemide, cipro, cephalosporins
NB. False +ve: myoglobin, porphyria

Interpretation
Isolated urea = flow (i.e. hypoperfusion / dehydration)
U and Cr = filtration (i.e. renal failure)
Proteinuria
30mg/dL = 1+
300mg/dL = 3+ Creatinine Clearance
PCR < 20mg/mM is normal, >300 = nephrotic Vol of blood that can be cleared of a substance in 1min
CrC roughly approximates GFR as it is freely filtered and
Causes only a small proportion secreted (~10%)
Commonest Slightly overestimates GFR
DM Requires urine concentration from 24h collection
Minimal change Can use radiolabelled EDTA: very rarely done
Membranous
Amyloidosis
SLE
Other
eGFR
HTN (inc. PET) Modifiation of Diet in Renal Disease (MDRD) equation
ATN Serum Cr, sex, age, race
TIN Obviates need for urine collection
UTI
Fever, orthostatic Problems
Validated for patients
c established renal failure:
NB. False ve: Bence-Jones protein ?applicable to general population.
Most elderly people are in stage 3 CRF by eGFR:
Microalbuminuria may not progress or impinge on their health.
Albumin 30-300mg/24h eGFR is too pessimistic in mild renal impairment
Causes: DM, BP, minimal change GN
Casts
RBC: glomerular haematuria
WBC: interstitial nephritis or pyelonephritis
Tubular: ATN
Differential
Pathology Urine
Glomerular Haematuria, proteinuria, red cells / casts
Tubular White cell casts, small protein, leukocyturia
Pre-renal Nothing
CRF Depends on cause

Causes of Renal Disease Presentation of Renal Failure
Pre-renal Uraemia (need GFR <15ml/min)
Shock
Renal Vascular Symptoms Signs
RAS
Toxins: NSAIDs, ACEi Pruritus Pale, sallow skin
Thrombosis n/v, anorexia, wt. loss Striae
Hepatorenal syn. Lethargy Pericardial or plueral rub
Confusion Fits
Restless legs Coma
Renal Metallic taste
Glomerulonephritis Paraesthesia: neuropathy
Acute Tubular Necrosis Bleeding
Interstitial disease Chest pain: serositis
Hiccoughs
Post-renal
Diseases of renal papillae, pelvis, ureters, bladder or
Protein loss and Na+ retention
urethra.
Symptoms Signs
SNIPPIN
Stone
Neoplasm Polyuria, polydipsia Oedema
Inflammation: stricture Oliguria, anuria JVP
Prostatic hypertrophy Breathlessness HTN (or BP)
Posterior urethral valves
Infection: TB, schisto
Neuro: post-op, neuropathy Acidosis
Symptoms Signs
Breathlessness Kussmaul respiration

Confusion
Hyperkalaemia
Symptoms Signs
Palpitations Peaked T waves

Chest pain Flattened P waves
Weakness PR interval
Widened QRS
Sine-wave pattern VF
Anaemia
Symptoms Signs
Breathlessness Pallor
Lethargy Tachycardia
Faintness Flow mumurs (ESM @ apex)
Tinnitus
Vitamin D Deficiency
Symptoms Signs
Bone pain Osteomalacia

#s - Loosers zones (pseudo#s)
- Cupped mataphyses

Urinary Tract Infection
Definitions Risk Factors
Bacteriuria: bacteria in urine, symptomatic or asympto Female
UTI: symptomatic c +ve culture or dipstick Sex
Urethral Syndrome: symptomatic but no bacteriuria Pregnancy
Menopause
Classification DM
Uncomplicated: normal GU tract and function Abnormal tract: stone, obstruction, catheter,
Complicated: abnormal GU tract, outflow obstruction, malformation
renal function, impaired host defence, virulent organism
Recurrent: further infection
c new organism
Relapse: further infection
c same organism Organisms
E. coli
Staphylococcus saprophyticus
Presentation Proteus (alkaline urine struvite renal stones)
Klebsiella
Pyelonephritis
Fever, rigors
Loin pain and tenderness Ix
Vomiting Dipstick
Oliguria if ARF MSU for MCS
Bloods: FBC, U+E, blood cultures (if systemic signs)
Cystitis US: children, men, recurrence, pyelonephritis
Frequency and urgency
Polyuria Positive Culture
Haematuria >104 CFU/ml pure growth
Dysuria >103 CFU/ml pure growth of E. coli or S. saprophyticus
Suprapubic tenderness >105 CFU/ml mixed growth
c one predominant organism
Foul smelling urine
Prostatitis Rx
Flu-like symptoms
Low backache General
Dysuria Drink plenty, urinate often
Tender swollen prostate on PR
Cystitis
Rx for 3-6d
Sterile Pyuria Trimethoprim 200mg BD
TB Nitrofurantoin 50mg QDS (not in RF)
Treated UTI Cefalexin 500mg BD (good in RF)
Appendicitis Co-amoxiclav 625mg TDS
Calculi
TIN Pyelonephritis
Papillary necrosis Cefotaxime 1g IV BD for 10d
Polycystic Kidney No response: Augmentin 1.2g IV TDS + gentamicin
Chemical cystitis (e.g. cyclophosphamide)
Prevention
Drink more
Abx prophylaxis
? cranberry juice

Glomerulonephritis Asymptomatic Haematuria
Features Causes
1. IgA Nephropathy
Group of disorders resulting from glomerular damage
2. Thin BM
Can proteinuria haematuria
3. Alports
Can AKI or ESRF
1. IgA Nephropathy / Bergers Disease

Presentations Commonest GN in developed world
Asymptomatic haematuria
Nephrotic syndrome Features
Nephritic syndrome Young male c episodic macroscopic haematuria
occurring a few days after URTI.
Rapid recovery between attacks
Causes IgA
Idiopathic Can occasionally nephritic syndrome
Immune: SLE, Goodpastures, vasculitis
Infection: HBV, HCV, Strep, HIV Biopsy: IgA deposition in mesangium
Drugs: penicillamine, gold
Amyloid Rx: Steroids or cyclophosphamide if renal function
Prognosis: 20% ESRF after 20yrs

Ix
Blood 2. Thin BM Disease
Basic: FBC, U+E, ESR Autosomal dominant
Complement (C3 and C4) Commonest cause of asymptomatic haematuria
Abs: ANA, dsDNA, ANCA, GBM
Serum protein electrophoresis and Ig Features
Infection: ASOT, HBC and HCV serology Persistent, asymptomatic microscopic haematuria
V. small risk of ESRF
Urine
Dipstick: proteinuria haematuria
Spot PCR 3. Alports Syndrome
MCS 85% X-linked inheritance
Bence-Jones protein
Features
Imaging Haematuria, proteinuria progressive renal failure
CXR: infiltrates (Goodpastures, Wegeners) Sensorineural deafness
Renal US biopsy Lens dislocation and cataracts
Retinal flecks
Females: haematuria only
General Mx
Refer to nephrologist
Rx HTN aggressively (130/80)
Include and ACEi / ARA

Nephritic Syndrome / Acute GN Nephrotic Syndrome
Haematuria (macro / micro) + red cell casts Proteinuria: PCR >300mg/mM or >3g/24h
Proteinuria oedema (esp. periorbital) Hypoalbuminaemia: <35g/L
Hypertension Oedema: periorbital, genital, ascites, peripheral
Oliguria and progressive renal impairment Often intravascularly depleted c JVP (cf. CCF)
Causes Complications
1. Proliferative / post-streptococcal Infection: Ig, complement activity
2. Crescentic / RPGN VTE: up to 40%
Hyperlipidaemia: cholesterol and triglycerides
1. Proliferative / Post-streptococcal Ix
As for GN, check lipids
Features
Biopsy
Young child develops malaise and nephritic syndrome c
All adults
smoky urine 1-2wks after sore throat or skin infection. Steroids 1st
c children: mostly minimal change
ASOT
C3
Secondary to Systemic Disease
Biopsy: IgG and C3 deposition DM: glomerulosclerosis
SLE: membranous
Rx: Supportive Amyloidosis
Prognosis 1. Minimal Change Glomerulonephritis

95% of children recover fully Commonest cause of nephrotic syndrome in children
Minority develop RPGN Assoc.: URTI
Biopsy: normal light micro, fusion of podocytes on EM
Rx: steroids
2. Crescentic / RPGN Prog: 1% ESRF
Most aggressive GN which can ESRF in days
2. Membranous Nephropathy
Type 1: Anti-GBM (Goodpastures) 5% 20-30% of adult nephrotic syndrome
Ab to NC domain of collagen 4 Associations
Haematuria and haemoptysis Ca: lung, colon, breast
CXR shows infiltrates AI: SLE, thyroid disease
Rx: Plasmapheresis and immunosuppression Infections: HBV
Drugs: Penicillamine, gold
Type 2: Immune Complex Deposition 45% Biopsy: subepithelial immune complex deposits
Complication of any immune complex deposition Rx: immunosuppression if renal function declines
Bergers, post-strep, endocarditis, SLE Prog: 40% spontaneous remission
Type 3: Pauci Immune 50% 3. FSGS

cANCA: Wegeners Commoner in Afro-Caribs
pANCA: microscopic polyangiitis, Churg-Strauss
Idiopathic or Secondary: VUR, Bergers, SCD, HIV
Even if ANCA+ve, may still be idiopathic Biopsy: focal scarring, IgM deposition
i.e. no features of systemic vasculitis
Rx: steroids or cyclophosphamide/ciclosporin
Prog: 30-50% ESRF (may recur in transplants)
5. Membranoproliferative / Mesangiocapillary GN
Rare
May nephrotic (60%) or nephritic (30%) syndrome
Asooc.
c HBV, HCV, endocarditis
Prog: 50% ESRF
Mx
Monitor U+E, BP, fluid balance, wt.
Treat underlying cause
Symptomatic / Complication Rx:
Oedema: salt and fluid restrict + frusemide
Proteinuria: ACEi / ARA proteinuria
Lipids: Statin
VTE: Tinzaparin
Rx HTN

Acute Kidney Injury
Definition RIFLE Classification
Significant decline in renal function over hrs or days 3 grades of AKI and 2 outcomes
manifesting as an abrupt and sustained in Se U and Cr Classification determined by worst criteria
Causes (Pre-renal and ATN account for ~80%) Classification GFR UO

Risk Cr x1.5 <0.5ml/kg/h x 6h
Pre-renal: commonest cause GFR >25%
Shock or renovascular compromise (e.g. NSAIDs, ACEi) Injury Cr x 2 <0.5ml/kg/h x 12h
GFR >50%
Renal Failure Cr x 3 <0.3ml/kg/h x 24h, or
ATN: GFR >75% anuria x12h
Ischaemia: shock, HTN, HUS, TTP Loss Persistent ARF = complete LOF >1mo
Direct nephrotoxins: drugs, contrast, Hb ESKD complete LOF >3mo
Acute TIN: drug hypersensitivity
Nephritic syndrome
Rx
Post-renal: SNIPPIN
General
Identify and Rx pre-renal or post-renal causes
Presentation Urgent US
Uraemia / Azotaemia Rx exacerbating factors: e.g. sepsis
Acidosis Give PPIs
Hyperkalaemia Stop nephrotoxins: NSAIDs, ACEi, gent, vanc
Fluid overload Stop metformin if Cr > 150mM
Oedema, inc. pulmonary
BP (or ) Monitor
S3 gallop Catheterise and monitor UO
JVP Consider CVP
Fluid balance
Clinical Assessment Wt.
1. Acute or chronic?
Cant tell for sure: Rx as acute Hyperkalaemia
Chronic features ECG Features (in order)
Hx of comorbidity: DM, HTN Peaked T waves
Long duration of symptoms Flattened P waves
Previously abnormal bloods (GP records) PR interval
Widened QRS
2. Volume depleted? Sine-wave pattern VF
Postural hypotension Mx
JVP 10ml 10% calcium gluconate
pulse 100ml 20% glucose + 10u insulin (Actrapid)
Poor skin turgor, dry mucus membranes Salbutamol 5mg nebulizer
Calcium resonium 15g PO or 30g PR
3. GU tract obstruction? Haemofiltration (usually needed if anuric)
Suprapubic discomfort
Palpable bladder Pulmonary Oedema
Enlarged prostate Sit up and give high-flow O2
Catheter Morphine 2.5mg IV ( metoclopramide 10mg IV)
Complete anuria (rare in ARF) Frusemide 120-250mg IV over 1h
GTN spray ISMN IVI (unless SBP <100)
4. Rare cause? If no response consider:
Assoc.
c proteinuria haematuria CPAP
Vasculitis: rash, arthralgia, nosebleed Haemofiltration / haemodialysis venesection
Bleeding
Ix
urea impairs haemostasis
Bloods: FBC, U+E, LFT, glucose, clotting, Ca, ESR
FFP + plats as needed
ABG: hypoxia (oedema), acidosis, K+
Transfuse to maintain Hb >10
GN screen: if cause unclear
Urine: dip, MCS, chemistry (U+E, PCR, osmolality, BJP) Indications for Acute Dialysis (AEIOU)
ECG: hyperkalaemia 1. Persistent hyperkalaemia (>7mM)
CXR: pulmonary oedema 2. Refractory pulmonary oedema
Renal US: Renal size, hydronephrosis 3. Symptomatic uraemia: encephalopathy, pericarditis
4. Severe metabolic acidosis (pH <7.2)
NB. in pre-renal failure, urine is concentrated and Na is 5. Poisoning (e.g. aspirin)
reabsorbed osmolality, Na <20mM
Management of Acute Renal Failure
Common Causes
Pre-renal: shock (e.g. sepsis, hypovolaemia), HRS Resuscitate and Assess Fluid Status
Renal: ATN, TIN, GN A: GCS may need airway Mx
Post-renal: Stone, neoplasm, catheter B: pulmonary oedema sit up, high flow O2
C: Assess fluid status:
CV Tissues End-organ
Presentation Postural BP CRT Mental state
Usually presents in the context of critical illness JVP Cold / warm hands Urine output
Uraemia HR Skin turgor
Hyperkalaemia Mucus membranes
Acidosis
Oedema and BP
Rx Life-Threatening Complications
Ix Hyperkalaemia
Bloods: FBC, U+E, LFT, glucose, clotting, Ca, ESR Pulmonary oedema
ABG: hypoxia (oedema), acidosis, K+ Consider need for rapid dialysis
Urine: dip, MCS, chemistry (U+E, CRP, osmolality, BJP)
ECG: hyperkalaemia Rx Shock or Dehydration
CXR: pulmonary oedema Fluid challenge 250-500ml over 30min
Renal US: Renal size, hydronephrosis Repeat as necessary: aim for CVP of 5-10cm
Once replete, continue @ 20ml+UO/h
Hyperkalaemia
ECG Features (in order)
Peaked T waves Monitor
Flattened P waves Cardiac monitor
PR interval Urinary catheter
Widened QRS Consider CVP
Sine-wave pattern VF Start fluid balance chart
Mx
10ml 10% calcium gluconate
50ml 50% glucose + 10u insulin (Actrapid)
Salbutamol 5mg nebulizer Look for Evidence of Post-Renal Causes
Calcium resonium 15g PO or 30g PR Palpable tender bladder
Haemofiltration (usually needed if anuric) Enlarged prostate
Catheter in situ
Complete anuria
Pulmonary Oedema
Sit up and give high-flow O2
Morphine 2.5mg IV ( metoclopramide 10mg IV)
Hx and Ix
Frusemide 120-250mg IV over 1h
Hx: Evidence of Acute vs. Chronic RF
Duration of symptoms
If no response consider:
Co-morbidities
CPAP
Haemofiltration / haemodialysis venesection Previous blood results
Ix
Bloods, ABG
Indications for Acute Dialysis (AEIOU)
Urine dip + MCS + chem
1. Persistent hyperkalaemia (>7mM)
2. Refractory pulmonary oedema ECG
3. Symptomatic uraemia: encephalopathy, pericarditis CXR and Renal US
5. Poisoning (e.g. aspirin)
Rx Sepsis
Blood cultures and empirical Abx
Further Mx
Call urologists if obstructed despite catheter
Care with nephrotoxic drugs: e.g. gentamicin

Interstitial Nephritidies Nephrotoxins
Either directly toxic ATN
Acute Interstitial / Tubulointerstitial Nephritis Or cause hypersensitivity TIN
Immune-mediated hypersensitivity
c either drugs or
other Ag acting as haptans Exogenous
NSAIDs
Causes Antimicrobials: AVASTA
Drug hypersensitivity in 70% Aminoglycosides
NSAIDs Vancomycin
Abx: Cephs, penicillins, rifampicin, sulphonamide Aciclovir
Diuretics: frusemide, thiazides Sulphonamides
Allopurinol Tetracycline
Cimetidine Amphotericin
Infections in 15% ACEi
Staphs, streps Immunosuppressants
Immune disorders Ciclosporin
SLE, Sjogrens Tacrolimus
Contrast media
Presentation Anaesthetics: enflurane
Fever, arthralgia, rashes
AKI olig/anuria
Uveitis Endogenous
Haemoglobin, myoglobin
Ix
Urate
IgE, eosinophilia
Ig: e.g. light chains in myeloma
Dip: haematuria, proteinuria, sterile pyuria
Rx
Stop offending drug Rhabdomyolysis
Prednisolone
Pathogenesis
Prognosis: Most recover renal function Skeletal muscle breakdown release of:
K+, PO4, urate
Chronic TIN Myoglobin, CK
Fibrosis and tubular loss K and AKI
Commonly caused by:
Causes
Reflux and chronic pyelonephritis
DM Ischaemia: embolism, surgery
SCD or trait Trauma: immobilisation, crush, burns, seizures,
compartment syndrome
Toxins: statins, fibrates, ecstasy, neuroleptics
Analgesic Nephropathy
Prolonged heavy ingestion of compound analgesics
Clinical
Often a Hx of chronic pain: headaches, muscle pain Muscle pain, swelling
Red/brown urine
Features
AKI occurs 10-12h later
Sterile pyuria mild proteinuria
Slowly progressive CRF
Ix
Sloughed papilla can obstruction and renal colic Dipstick: +ve Hb, -ve RBCs
Blood: CK, K, PO4, urate
Ix: CT w/o contrast (papillary calcifications)
Rx: stop analgesics
Rx
Rx hyperkalaemia
Acute Urate Crystal Nephropathy IV rehydration: 300ml/h
AKI due to urate precipitation CVP monitoring if oliguric
Usually after chemo-induced cell lysis IV NaHCO3 may be used to alkalinize urine and stabilise
Rx: hydration, urinary alkalinisation a less toxic form of myoglobin.
Nephrocalcinosis
Diffuse renal parenchymal calcification
Progressive renal impairment
Causes
Malignancy
PTH
Myeloma
Sarcoidosis
Vit D intoxification
RTA
Chronic Renal Failure
Features Renal Osteodystrophy
Kidney damage 3mo indicated by function
Symptoms usually only occur by stage 4 (GFR<30) Features
ESRF is stage 5 or need for RRT Osteoporosis: bone density
Osteomalacia: mineralisation of osteoid (matrix)
Classification 2O/3O HPT osteitis fibrosa cystica
Subperiosteal bone resorption
Stage GFR Acral osteolysis: short stubby fingers
1 >90 Pepperpot skull
2 60-89 May get spinal osteosclerosis Rugger Jersey spine
3a 45-59 Sclerotic vertebral end-plate
c lucent centre
3b 30-44
4 16-29 Mechanism
5 <15 1-hydroxylase vit D activation Ca PTH
Phosphate retention Ca and PTH (directly)
Causes PTH activation of osteoclasts osteoblasts
Common Also acidosis bone resorption
DM
HTN Mx
Other
RAS General
GN Rx reversible causes
Polycystic disease Stop nephrotoxic drugs
Drugs: e.g. analgesic nephropathy
Pyelonephritis: usually 2O to VUR Lifestyle
SLE Exercise
Myeloma and amyloidosis Healthy wt.
Stop smoking
Hx Na, fluid and PO4 restriction
Past UTI
HTN, DM CV Risk
FH Statins (irrespective of lipids)
DH Low-dose aspirin
Symptoms Rx DM
Ix Hypertension
Blood Target <140/90 (<130/80 if DM)
Hb, U+E, ESR, glucose, Ca/PO4, ALP, PTH In DM kidney disease give ACEi/ARB (inc. if normal BP)
Immune: ANA, dsDNA, ANCA, GBM, C3, C4, Ig, Hep
Oedema
Film: burr cells
Frusemide
Urine: dip, MCS, PCR, BJP
Bone Disease
Imaging Phosphate binders: sevelamer, calcichew
CXR: cardiomegaly, pleural/pericardial effusion, oedema Vit D analogues: alfacalcidol (1 OH-Vit D3)
AXR: calcification from stones Ca supplements
Renal US Cinacalcet: Ca mimetic
Usually small (<9cm)
May be large: polycystic, amyloid Anaemia
Bone X-rays: renal osteodystrophy (pseudofractures) Exclude IDA and ACD
CT KUB: e.g. cortical scarring from pyelonephritis EPO to raise Hb to 11g/dL (higher = thrombosis risk)
Renal biopsy: if cause unclear and size normal Restless Legs

Clonazepam
Complications: CRF HEALS
Cardiovascular disease
Renal osteodystrophy
Fluid (oedema)
HTN
Electrolyte disturbances: K, H
Anaemia
Leg restlessness
Sensory neuropathy

Renal Transplant
Treatment of choice for ESRF Complications
Assessment Post-op
Virology status: CMV, HCV, HBV, HIV, VZV, EBV Bleeding
CVD Graft thrombosis
TB Infection
ABO and HLA haplotype Urinary leaks
Hyperacute rejection (minutes)

Contraindications ABO incompatibility
Active infection Thrombosis and SIRS
Cancer
Severe HD or other co-morbidity Acute Rejection (<6mo)
ing Cr ( fever and graft pain)
Cell-mediated response
Types of Graft Responsive to immunosuppression
Cadaveric: brainstem death
c CV support
Non-heart beating donor: no active circulation Chronic Rejection (>6mo)
Live-related Interstitial fibrosis + tubular atrophy
Optimal surgical timing Gradual in Cr and proteinuria
HLA-matched Not responsive to immunosuppression
Improved graft survival
Live unrelated Ciclosporin / tacrolimus nephrotoxicity
Acute: reversible afferent arteriole constriction GFR
Chronic: tubular atrophy and fibrosis
Immunosuppression
Pre-op: campath / alemtuzumab (anti-CD52) Immune Function
Post-op: prednisolone short-term and tacro/ciclo long- risk of infection: opportunists, fungi, warts
term risk of malignancy: BCC, SCC, lymphoma (EBV)
Cardiovascular Disease
Prognosis Hypertension and atherosclerosis
t for cadaveric grafts: 15yrs
Differential of Rising Cr in Tx pt.

Rejection
Obstruction
ATN
Drug toxicity

Renal Complications of Systemic Disease
Diabetic Nephropathy Myeloma
Causes ~20% of ESRF
Advanced / ESRF occurs in 40% of T1 and T2 DM Pathology
Excess production of monoclonal Ab light chains
Pathology (excreted and detected in 60% as urinary BJP).
Diabetic nephropathy describes conglomerate of lesions Light chains block tubules and have direct toxic effects
occurring concurrently. ATN.
Hyperglycaemia renal hyperperfusion hypertrophy Myeloma also assoc. c Ca2+
and renal size
Hypertrophy and metabolic defects inc. ROS production Presentation
glomerulosclerosis and nephron loss ARF / CRF
Nephron loss RAS activation HTN Amyloidosis
Clinically Rx
Microalbuminuria (30-300mg/d or albumin:creatinine >3) Ensure fluid intake of 3L/d to prevent further impairment
Strong independent RF for CV disease Dialysis may be required in ARF
Progresses to proteinuria (albuminuria >300mg/d)
Diabetic retinopathy usually co-exists and HTN is
common Rheumatological Disease
Screening RA
T2DMs should be screened for microalbuminuria 6moly NSAIDs ATN
Penicillamine and gold membranous GN
Rx AA amyloidosis occurs in 15%
Good glycaemic control delays onset and progression
BP target 130/80 SLE
Start ACEi/ARB even if normotensive Involves glomerulus in 40-60% ARF/CRF
Stop smoking Proteinuria and BP common
Combined kidney pancreas Tx possible in selected pts Rx
Proteinuria: ACEi
Aggressive GN: immunosuppression
Amyloidosis
Renal involvement usually caused by AL/AA amyloid Diffuse Systemic Sclerosis
Features: Renal crisis: malignant HTN + ARF
Proteinuria Commonest cause of death
Nephrotic syndrome Rx: ACEi if BP or renal crisis
Progressive renal failure
Dx
Large kidneys on US
Biopsy
Infection
GN: post-strep, HCV, HBV, HIV, SBE/IE, visceral
abscess
Vasculitis: HBV, HCV, post-strep
TIN: bacterial pyelonephritis, CMV, HBV, toxo
Malignancy
Direct
Renal infiltration: leukaemia, lymphoma
Obstruction: pelvic tumour
Mets
Nephrotoxicity
Toxic chemo
Analgesics
Tumour lysis syndrome
Hyperparathyroidism
hypercalcaemia
Sarcoidosis
Ca and TIN
Renal Vascular Disease Renal Tubular Disease
Hypertension Renal Tubular Acidosis
HTN can be both the cause and effect of renal damage. Impaired acid excretion hyperchloraemic met acidosis
Renal diseases are commonest causes of 2O HTN Both RAS activation K+ wasting and hypokalaemia
Activation of RAS
Retention of Na and water due to excretion Type 1 (Distal)
Inability to excrete H+, even when acidotic
Renovascular Disease: RAS May complicate other renal disorders
Causes
Cause Hereditary: Marfans, Ehlers Danlos
Atherosclerosis in 80% AI: Sjogrens, SLE, thyroiditis
Fibromuscular dysplasia Drugs
Thromboembolism Features
External mass compression Rickets / osteomalacia (bone buffering)
Renal stones and UTIs
Features Nephrocalcinosis ESRF
Refractory hypertension Dx
Worsening renal function after ACEi/ARB Failure to acidify urine (pH >5.5) despite acid load
Flash pulmonary oedema (no LV impairment on echo)
Type 2 (Proximal)
Ix Defect in HCO3 reabsorption in PCT
US + doppler: small kidney + flow Tubules can reabsorb some HCO3 so can acidify urine in
CT/MR angio systemic acidosis when HCO3
Renal angiography: gold standard Usually assoc. c Fanconi syndrome
Dx
Rx Urine will acidify
c acid load (pH <5.5)
Rx medical CV risk factors
Angioplasty and stenting Fanconi Syndrome
Disturbance of PCT function generalised impaired
reabsorption
Haemolytic Uraemic Syndrome (HUS) amino acids, K+, HCO3, phosphate, glucose
E. coli O157:H7: verotoxin endothelial dysfunction Causes
Idiopathic
Features Inherited: inborn errors, Wilsons
Young children eating undercooked meat (burgers) Acquired: tubule damage (drugs, myeloma)
Bloody diarrhoea and abdominal pain precedes: Features
MAHA Polyuria (osmotic diuresis)
Thrombocytopenia Hypophosphataemic rickets (Vit D resistant)
Renal failure Acidosis, K
Ix Hereditary Hypokalaemic Tubulopathies

Schistocytes, plats Bartters Syndrome
Blockage of NaCl reabsorption in loop of Henle
Hb
(as if taking frusemide)
Normal clotting
Congenital salt wasting RAS activation
hypokalaemia and metabolic alkalosis
Rx
Normal BP
Usually resolves spontaneously
Gitelman Syndrome
Dialysis or plasma exchange may be needed Blockage of NaCl reabsorption in DCT (as if
taking thiazides)
Congenital salt wasting RAS activation
Thrombotic Thrombocytopenia Purpura (TTP) hypokalaemia and metabolic alkalosis +
Genetic or acquired deficiency of ADAMTS13 giant hypocalciuria
vWF multimers Normal BP
Features
Adult females
Pentad
Fever
CNS signs: confusion, seizures
MAHA
Thrombocytopenia
Renal failure
Ix: As HUS
Rx: Plasmapheresis, immunosuppression, splenectomy

Renal Cystic Diseases
Auto Dom Polycystic Kidney Disease
Prev: 1:1000 Auto Rec Polycystic Kidney Disease
Age: Adults 40-60yrs Prev: 1:40,000
Genetics Infancy
PKD1 on Chr16, polycystin 1 (80%): cell-cell and cell- Renal cysts and congenital hepatic fibrosis
matrix membrane receptor
PKD2 on Chr4, polycystin 2: Ca2+ channel that
interacts
c polycystin 1
Medullary Sponge Kidney
Path
Multiple cystic dilatations of the CDs in the medulla
Large cysts arising from all parts of nephron
Progressive decline in renal function Typically presents in 20-30s
70% ESRF by 70yrs Commoner in females
Often asymptomatic, but predisposes to
Presentation: MISSHAPES Hypercalciuria and nephrolithiasis
Mass: abdo mass and flank pain Recurrent UTIs and pyelonephritis
Infected cyst Haematuria
Stones Renal function is usually normal
SBP
Haematuria or haemorrhage into cyst
Aneurysms: berry SAH Tuberous Sclerosis (Bournevilles Disease)
Polyuria + nocturia AD condition
c hamartomas in skin, brain, eye,
Extra-renal cysts: liver kidney
Systolic murmur: mitral valve prolapse Skin: nasolabial adenoma sebaceum, ash-leaf
macules, peri-ungual fibromas
Rx Neuro: IQ, epilepsy
General Renal: cysts, angiomyolipomas
water intake, Na, caffeine (may cyst formation)
Monitor U+E and BP
Genetic counselling Renal Enlargement Differential: PHONOS
MRA screen for Berry aneurysms Polycystic kidneys: ADPKD, ARPKD, TS
Medical Hypertrophy 2O to contralateral renal agenesis
Rx HTN aggressively: <130/80 (ACEi best) Obstruction (hydronephrosis)
Rx infections Neoplasia: RCC, myeloma, amyloidosis
Surgical Occlusion (renal vein thrombosis)
Pain may be helped by laparoscopic cyst removal or Systemic: early DM, amyloid
nephrectomy.
ESRF in 70% by 70yrs
Dialysis or transplant

Haematology
Contents
Anaemia Classification and Causes .......................................................................................................................................... 119
Microcytic Anaemia ................................................................................................................................................................... 120
Macrocytic Anaemia .................................................................................................................................................................. 121
Haemolytic Anaemias ................................................................................................................................................................ 122
Sickle Cell Disease .................................................................................................................................................................... 123
Bleeding Diatheses.................................................................................................................................................................... 124
Thrombophilia ............................................................................................................................................................................ 125
Blood Transfusion...................................................................................................................................................................... 126
Bone Marrow Failure ................................................................................................................................................................. 127
Myelodysplastic Syndromes ...................................................................................................................................................... 127
Chronic Myeloproliferative Disorders ........................................................................................................................................ 128
Acute Lymphoblastic Leukaemia............................................................................................................................................... 129
Acute Myeloid Leukaemia ......................................................................................................................................................... 129
Chronic Lymphocytic Leukaemia .............................................................................................................................................. 130
Chronic Myeloid Leukaemia ...................................................................................................................................................... 130
Non-Hodgkins Lymphoma ........................................................................................................................................................ 131
Hodgkins Lymphoma ................................................................................................................................................................ 131
Multiple Myeloma....................................................................................................................................................................... 132
Other Paraproteinaemias .......................................................................................................................................................... 133
Amyloidosis ............................................................................................................................................................................... 133
Complications of Haematological Malignancies ........................................................................................................................ 134
Spleen and Splenectomy .......................................................................................................................................................... 135
The Lab ..................................................................................................................................................................................... 136

Anaemia Classification and Causes
Low Hb Haemolytic Anaemia
Men: <13.5g/dl
Women: <11.5g/dl red cell breakdown
1. Anaemia c MCV + polychromasia = reticulocytosis
2. unconjugated bilirubin
Symptoms 3. urinary urobilinogen
4. se LDH
Fatigue
5. Bile pigment stones
Dyspnoea
Faintness Intravascular
Palpitations 1. Haemoglobinaemia
Headache 2. Haemoglobinuria
Tinnitus 3. se haptoglobins
4. urine haemosiderin
5. Methaemalbuminaemia
Signs
Pallor Extravascular
Hyperdynamic circulation 1. Splenomegaly
Tachycardia
Flow murmur: apical ESM Acquired
Cardiac enlargement Immune-mediated DAT+ve
Ankle swelling
c heart failure AIHA: warm, cold, PCH
Drugs: penicillin, quinine, methyldopa
Allo-immune: acute transfusion reaction, HDFN
PNH
Microcytic
Mechanical:
Haem Defect
MAHA: DIC, HUS, TTP
IDA
Heart valve
ACD
Infection: malaria
Sideroblastic / lead poisoning
Burns
Globin Defect
Thalassaemia
Hereditary
Enzyme: G6PD and pyruvate kinase deficiency
Membrane: HS, HE
Normocytic
Haemoglobinopathy: SCD, thalassaemia
Recent blood loss
Bone marrow failure
Renal failure
Early ACD
Pregnancy ( plasma volume)
Macrocytic
Megaloblastic
Vit B12 or folate deficiency
Anti-folate drugs: phenytoin, methotrexate
Cytotoxics: hydroxycarbamide
Non-megaloblastic
Reticulocytosis
Alcohol or liver disease
Hypothyroidism
Myelodysplasia

Microcytic Anaemia
IDA Thalassaemia
Signs Pathophysiology
Koilonychia Point mutations () / deletions () unbalanced
Angular stomatitis / cheilosis production of globin chains
Post-cricoid Web: Plummer-Vinson precipitation of unmatched globin
membrane damage haemolysis while still in BM
Causes and removal by the spleen
Mechanism Examples Epidemiology

Loss Menorrhagia Common in Mediterranean and Far East
GI bleeding
Hookworms Thalassaemia Trait / Heterozygosity
+ O
/ ( production) or / (no production)
Intake Poor diet Mild anaemia which is usually harmless
MCV (too low for the anaemia): e.g. <75
Malabsorption Coeliac HbA2 (2 2) and HbF (22)
Crohns
Thalassaemia Major
Ix O / O or O / + or + / +
Haematinics: ferritin, TIBC, transferrin saturation Features develop from 3-6mo
Film: Anisocytosis, poikilocytosis, pencil cells Severe anaemia
Upper and lower GI endoscopy Jaundice
FTT
Rx Extramedullary erythropoiesis
Ferrous sulphate 200mg PO TDS Frontal bossing
SE: GI upset Maxillary overgrowth
HSM
Haemochromatosis after 10yrs (transfusions)
Sideroblastic Anaemia Ix
Ineffective erythropoiesis Hb, MCV, HbF, HbA2 variable
iron absorption Film: Target cells and nucleated RBCs
Iron loading in BM ringed sideroblasts Rx
Haemosiderosis: endo, liver and cardiac damage Life-long transfusions
SC desferrioxamine Fe chelation
Causes BM transplant may be curative
Congenital
Acquired Thalassaemia
Myelodysplastic / myeloproliferative disease Trait
Drugs: chemo, anti-TB, lead --/ or -/-
Asymptomatic
Ix Hypochromic microcytes
Microcytic anaemia not responsive to oral iron HbH Disease
Ferritin, se Fe, TIBC --/-
Moderate anaemia: may need transfusions
Rx Haemolysis: HSM, jaundice
Remove cause Hb Barts
Pyridoxine may help --/--
Hydrops fetalis death in utero

Macrocytic Anaemia
Ix B12 Deficiency
Film Vit B12
B12/Folate Source: meat, fish and dairy (vegans get deficient)
Hypersegmented PMN Stores: 4yrs
Oval macrocytes Absorption: terminal ileum bound to intrinsic factor
EtOH/Liver (released from gastric parietal cells)
Target cells Role: DNA and myelin synthesis
Blood Causes
LFT: mild bilirubin in B12/folate deficiency
TFT Mechanism Examples
Se B12 Intake Vegan
Red cell folate: reflects body stores over 2-3mo
intrinsic factor Pernicious anaemia
BM biopsy: if cause not revealed by above tests Post-gastrectomy
Megaloblastic erythropoiesis
Giant metamyelocytes Terminal ileum Crohns
Ileal resection
Bacterial overgrowth
Folate Deficiency
Features
General
Folate
Symptoms of anaemia
Source: Green veg, nuts, liver
Lemon tinge: pallor + mild jaundice
Stores: 4mo
Glossitis (beefy, red tongue)
Absorption: proximal jejunum
Neuro
Paraesthesia
Causes Peripheral neuropathy
Optic atrophy
Mechanism Examples SACD
Intake Poor diet
Subacute Combined Degeneration of the Cord
Demand Pregnancy Usually only caused by pernicious anaemia
Haemolysis
Combined symmetrical dorsal column loss and
Malignancy
corticospinal tract loss.
distal sensory loss: esp. joint position and vibration
Malabsorption Coeliac
ataxia c wide-gait and +ve Rombergs test
Crohns
Mixed UMN and LMN signs
Drugs EtOH Spastic paraparesis
Phenytoin Brisk knee jerks
Methotrexate Absent ankle jerks
Upgoing plantars
Rx Pain and temperature remain intact
Assess for underlying cause
Give B12 first unless B12 level known to be normal Ix
May precipitate or worsen SACD WCC and plats if severe
Folate 5mg/d PO Intrinsic factor Abs: specific but lower sensitivity
Parietal cell Abs: 90% +ve in PA but specificity
Rx
Malabsorption parenteral B12 (hydroxocobalamin)
Replenish: 1mg/48h IM
Maintain: 1mg IM every 3mo
Dietary oral B12 (cyanocobalamin)
Parenteral B12 reverses neuropathy but not SACD
Pernicious Anaemia
Autoimmune atrophic gastritis caused by autoAbs vs.
parietal cells or IF achlorhydria and IF.
Usually >40yrs, incidence c blood group A
Associations:
AI: thyroid disease, Vitiligo, Addisons, HPT
Ca: 3x risk of gastric adenocarcinoma

Haemolytic Anaemias
AIHA
Hereditary Spherocytosis
Warm Commonest inherited haemolytic anaemia in N. Europe
IgG-mediated, bind @ 37OC
Extravascular haemolysis and spherocytes Pathophysiology
Ix: DAT+ve Autosomal dominant defect in RBC membrane
Causes: idiopathic, SLE, RA, Evans Spherocytes get trapped in spleen extravascular
Rx: immunosuppression, splenectomy haemolysis
Cold Features
IgM-mediated, bind @ <4OC Splenomegaly
Often fix complement intravascular haemolysis Pigment gallstones
May cause agglutination acrocyanosis or Raynauds Jaundice
Ix: DAT+ve for complement alone
Causes: idiopathic, mycoplasma Complications
Rx: avoid cold, rituximab Aplastic crisis
Megaloblastic crisis
Paroxysmal Cold Haemoglobinuria
Rare: assoc.
c measles, mumps, chickenpox Ix
IgG Donath-Landsteiner Abs bind RBCs in the cold and osmotic fragility
complement-mediated lysis on rewarming Spherocytes
DAT-ve
PNH
Rx
Absence of RBC anchor molecule (GPI) cell-surface
complement degradation proteins IV lysis Folate and splenectomy (after childhood)
Affects stem cells and may also plats + PMN
Features Hereditary Eliptocytosis

Visceral venous thrombosis (hepatic, mesenteric, CNS) Autosomal dominant defect elliptical RBCs
IV haemolysis and haemoglobinuria Most pts. are asymptomatic
Rx: folate, rarely splenectomy
Ix
Anaemia thrombocytopenia neutropenia
FACS: CD55 and CD59 G6PD deficiency
Rx Pathophysiology
Chronic disorder long-term anticoagulation X-linked disorder of pentose phosphate shunt
Eculizumab (prevents complement MAC formation) NADPH production RBC oxidative damage
Affects mainly Mediterranean and Mid / Far East
Haemolytic Uraemic Syndrome (HUS)
Features Haemolysis Triggers
E. coli O157:H7 from undercooked meat Broad (Fava) beans
Bloody diarrhoea and abdominal pain precedes: Mothballs (naphthalene)
MAHA Infection
Thrombocytopenia Drugs: antimalarials, henna, dapsone, sulphonamides
Renal failure
Ix
Ix: schistocytes, plats, normal clotting Film
Rx Irregularly contracted cells
Usually resolves spontaneously Bite cells, ghost cells and blister cells
Exchange transfusion or dialysis may be needed Heinz bodies
G6PD assay after 8wks (reticulocytes have high G6PD)
Thrombotic Thrombocytopenia Purpura (TTP)
Genetic or acquired deficiency of ADAMTS13 Rx
Features Treat underlying infection
Adult females Stop and avoid precipitants
Pentad Transfusion may be needed
Fever
CNS signs: confusion, seizures
MAHA Pyruvate Kinase Deficiency
Thrombocytopenia Autosomal recessive defect in ATP synthesis
Renal failure rigid red cells phagocytosed in the spleen
Features: splenomegaly, anaemia jaundice
Ix: schistocytes, plats, normal clotting Ix: PK enzyme assay
Rx: Plasmapheresis, immunosuppression, splenectomy Rx: often not needed or transfusion splenectomy
Sickle Cell Disease
Epidemiology Mx Chronic Disease
Africa, Caribbeans, Middle-East Pen V BD + immunisations
UK prevalence = 1/2000 Folate
Hydroxycarbamide if frequent crises
Pathogenesis
Point mutation in globin gene: gluval Mx Acute Crises
SCA: HbSS
Trait: HbAS General
HbS insoluble when deoxygenated sickling Analgesia: opioids IV
Sickle cells have life-span haemolysis Good hydration
Sickle cells get trapped in microvasc thrombosis O2
Keep warm
Ix Ix
Hb 6-9, retics, bilirubin FBC, U+E, reticulocytes, cultures
Film: sickle cells and target cells Urine dip
Hb electrophoresis CXR
Dx at birth c neonatal screening
Rx
Blind Abx: e.g. ceftriaxone
Presentation Transfusion: exchange if severe
Clinical features manifest from 3-6mo due to HbF
Triggers
Infection
Cold
Hypoxia
Dehydration
Splenomegaly: may sequestration crisis

Infarction: stroke, spleen, AVN, leg ulcers, BM
Crises: pulmonary, mesenteric, pain
Kidney disease
Liver, Lung disease
Erection
Dactylitis
Complications
Sequestration crisis
Splenic pooling shock + severe anaemia
Splenic infarction: atrophy and hyposplenism
infection: osteomyelitis
Aplastic crisis: parvovirus B19 infection
Gallstones

Bleeding Diatheses
Coagulation Tests Platelet Disorders
APTT Thrombocytopenia
Intrinsic: 12, 11, 9, 8 production
Common: 10, 5, 2, 1 BM failure: aplastic, infiltration, drugs (EtOH, cyto)
Increased Megaloblastic anaemia
Lupus anti-coagulant destruction
Haemophilia A or B Immune: ITP, SLE, CLL, heparin, viruses
vWD (carries factor 8) Non-immune: DIC, TTP, HUS, PNH, anti-
Unfractionated heparin phospholipid
DIC Splenic pooling
Hepatic failure Portal hypertension
SCD
PT
Extrinsic: 7 ITP
Common: 10, 5, 2, 1 Children: commonly post-URTI, self-limiting
Increased Adults: F>M, long-term
Warfarin / Vit K deficiency Ix: Anti-platelet Abs present
Hepatic failure Rx: conservative, steroids, IVIg, splenectomy
DIC
Functional Defects
Bleeding Time / PFA-100 Drugs: aspirin, clopidogrel
O
Platelet function 2 : paraproteinaemias, uraemia
Increased Hereditary
plats number or function Bernard-Soulier: GpIb deficiency
vWD Glanzmanns: GpIIb/IIIa deficiency
Aspirin
DIC
Coagulation Disorders
Thrombin Time
Fibrinogen function Acquired
Increased Severe liver disease
Quantitative/ qualitative fibrinogen defect Anticoagulants
DIC, dysfibrinogenaemia Vitamin K deficiency
Heparin
Haemophilia A: F8 Deficiency
Clinical Features X-linked, affects 1/5000 males
Pres: haemoarthroses, bleeding after surgery/extraction
Vascular or Platelet Disorder Ix: APTT, normal PT, F8 assay
Bleeding into skin: petechiae, purpura, echymoses Mx
Bleeding mucus mems: epistaxis, menorrhagia, gums Avoid NSAIDs and IM injections
Immediate, prolonged bleeding from cuts Minor bleeds: desmopressin + tranexamic acid
Major bleeds: rhF8
Coagulation Disorder
Deep bleeding: muscles, joints, tissues Haemophilia B: F9 deficiency
Delayed but severe bleeding after injury X-linked, 1/20,000 males
VWD
Vascular Disorders Commonest inherited clotting disorder (mostly AD)
vWF
Congenital Stabilises F8
HHT Binds plats via GpIb to damaged endothelium
Ehlers Danlos (easy bruising) Ix
Pseudoxanthoma elasticum If mild, APTT and bleeding time may be normal
APTT, bleeding time, normal plat, vWF AG
Acquired Rx: desmopressin + tranexamic acid
Senile purpura
Vitamin C deficiency DIC
Infection: e.g. meningococcus PT, APTT, TT, plats, fibrinogen, FDPs
Steroids Schistocytes
Vasculitis: e.g. HSP Thrombosis and bleeding
Causes: sepsis, malignancy (esp. APML), trauma, obs
Rx: FFP, plats, heparin

Thrombophilia
Definition Thrombophilia Screen
Coagulopathy predisposing to thrombosis, usually
venous. Indications
Arterial thrombosis <50yrs (?APL)
Inherited Venous thrombosis <40yrs c no RFs
Familial VTE
Factor V Leiden / APC resistance Unexplained recurrent VTE
Protein C deactivates F5 and F8 Unusual site: portal, mesenteric
c protein S and thrombomodulin cofactors Recurrent foetal loss
Degradation resistance present in 5% of population Neonatal
Most dont develop thrombosis
Heterozygotes: 5x VTE Investigations
Homozygotes: 50x VTE FBC, clotting, fibrinogen concentration
Factor V Leiden / APC resistance
Prothrombin Gene Mutation Lupus anticoagulant and anti-cardiolipin Abs
prothrombin levels Assays for AT, protein C and S deficiencies
thrombosis due to fibrinolysis by thrombin-activated PCR for prothrombin gene mutation
fibrinolysis inhibitor
Rx
Protein C and S Deficiency
Rx acute thrombosis as per normal
Heterozygotes for either have risk of thrombosis.
Anticoagulate to INR 2-3
Skin necrosis occurs esp. c warfarin
Consider lifelong warfarin
Heterozygotes neonatal purpura fulminans
If recurrence occurs on warfarin INR to 3-4
Antithrombin III Deficiency
AT is heparin co-factor thrombin inhibition Prevention
Deficiency affects 1/500 Lifelong anticoagulation not needed if asymptomatic
Heterozygotes have thrombosis risk VTE risk
c OCP or HRT
Homozygosity is incompatible c life Prophylaxis in high risk situations
Surgery
Pregnancy
Acquired
Progesterones in OCPs
Anti-phospholipid syndrome
CLOTs: venous and arterial
Coagulation defect: APTT
Livido reticularis
Obstetric complications: recurrent 1st
trimester abortion
Thrombocyotpenia

Blood Transfusion
Products FFP
Stored @ -18OC
Packed red cells Should be X-matched
Stored @ 4OC in SAGM Uses: DIC, liver disease, TTP, massive haemorrhage
Hct ~70%
Use to correct anaemia or blood loss Human Albumin Solution
1u Hb by 1-1.5g/dL Protein replacement
After abdominal paracentesis
Platelets Liver failure, nephrotic syndrome
Stored @ RT under agitation
Not needed if count >20 or not actively bleeding
Should be x-matched
Immediate Transfusion Reactions

Reaction Time Clinical Features Mechanism Rx
Haemolytic Minutes Agitation ABO incompatibility Stop transfusion
Fever IV haemolysis Tell lab
Abdo/chest pain Keep IV line open
c NS
BP shock Treat DIC
DIC haemorrhage
Renal failure
Bacterial <24h temp + rigors Bacterial proliferation Stop transfusion
Contamination BP Shock Esp. plats Send unit to lab
(Transfuse blood w/i 5h) Abx: Taz+gent
Febrile non- <24h Fever, rigors, chills Recipient anti-HLA Abs Slow transfusion
Haemolytic Paracetamol 1g
Allergic Immediate Urticaria, itch Recipient IgA deficiency Slow
Angioedoema Anti-IgA IgE Chlorphenamine 10mg IV/IM
Anaphylaxis
TRALI <6h ARDS: SOB, cough Anti-WBC Abs in donor plasma Stop transfusion
Bilat infiltrates on CXR Rx ARDS
Fluid <6h CCF Slow transfusion
Overload O2 + frusemide 40mg IV
Massive 24h K Whole blood vol in 24h Massive Transfusion Protocol
Transfusion Ca (citrate chelation) (5L = 10units) - 1:1:1 ratio of PRBC:FFP:PLT
F5 and F8 - survival
plats
Hypothermia Warm the blood
Delayed Transfusion Reactions

Reaction Time Clinical Features Mechanism Rx
Delayed 1-7d Jaundice Recipient anti-Rh Abs
Haemolytic Anaemia / ing Hb Extravasc haemolysis
Fever
Haemoglobinuria
Fe Overload Chronic SCA or Thal Major Chronic transfusions Desferrioxamine SC
Haemochromatosis
Post-transfusion 7-10d Thrombocytopenia AlloAbs attack recipient + donor plats IvIg
Purpura Purpura Plat transfusions
GvHD 4-30d Diarrhoea Viable lymphocytes transfused into
Skin rash immunocompromised host
Liver Failure LFTs
Pancytopaenia Irradiate blood for vulnerable hosts

Bone Marrow Failure Myelodysplastic Syndromes
Pancytopenia Pathophysiology
Heterogeneous group of disorders BM failure
Congenital Clone of stem cells
c abnormal development
Fanconis anaemia: aplastic anaemia functional defects
quantitative defects
Acquired May be primary or secondary
Idiopathic aplastic anaemia Chemo or radiotherapy
BM infiltration
Haematological Characteristics
Leukaemia Cytopenias
Lymphoma Hypercellular BM
Myelofibrosis Defective cells: e.g. ringed sideroblasts
Myelodysplasia
30% AML
Megaloblastic anaemia
Infection: HIV
Radiation
Clinical Features
Elderly
Drugs
Cytotoxic: cyclophos, azathioprine, methotrexate BM failure: anaemia, infection, bleeding, bruising
Abx: chloramphenicol, sulphonamides Splenomegaly
Diuretic: thiazides
Anti-thyroid: carbimazole Ix
Anti-psychotic: clozapine Film: blasts, Pelger-Huet anomaly, dimorphic
Anti-epileptic: phenytoin BM: Hypercellular, blasts, ringed sideroblasts
Mx
Aplastic Anaemia Supportive: transfusions, EPO, G-CSF
Rare stem cell disorder Immunosuppression
Allogeneic BMT: may be curative
Key Features
Pancytopenia
Hypocellular marrow
Presentation: Pancytopenia
Age: 15-24yrs and >60yrs
Anaemia
Infections
Bleeding
Causes
Inherited
Fanconis anaemia: Ashkenazi, short, pigmented
Dyskeratosis congenita: premature ageing
Swachman-Diamond syn.: pancreatic exocrine
dysfunction
Acquired
Drugs
Viruses: parvovirus, hepatitis
Autoimmune: SLE
Ix
BM: Hypocellular marrow
Mx
Supportive: transfusion
Immunosuppression: anti-thymocyte globulin
Allogeneic BMT: may be curative

Chronic Myeloproliferative Disorders
Classification Essential Thrombocythaemia
RBC Polycythaemia Vera
WBC CML Features
Platelets Essential thrombocythaemia Thrombosis
Megakaryocytes Myelofibrosis Arterial: strokes, TIA, peripheral emboli
Venous: DVT, PE, Budd-Chiari
Bleeding (abnormal plat function)
Polycythaemia Vera E.g. mucus membranes
Erythromelagia
Features
Hyperviscosity
Ix
Headaches
Plats >600 (often >1000)
Visual disturbances
Tinnitus BM: megakaryocytes
Thrombosis 50% JAK2+ve
Arterial: strokes, TIA, peripheral emboli
Rx
Venous: DVT, PE, Budd-Chiari
Plats 400-1000: aspirin alone
Histamine Release
Aquagenic pruritus Thrombosis or plats >1000: hydroxycarbamide
Erythromelalgia Anagralide may be used
Sudden, severe burning in hands and feet c Inhibits platelet maturation
plat count and function
redness of the skin
Splenomegaly: 75%
Prognosis
Hepatomegaly: 30%
5% AML/MF over 10yrs
Gout
Ix
99% JAK2+ve
Thrombocythaemia Differential
Primary: ET
RBC, Hb and Hct
Secondary:
WCC and plats
Bleeding
BM: hypercellular c erythroid marrow
Infection
EPO Chronic inflammation: RA, IBD
red cell mass
c isotope studies Trauma / surgery
Hyposplenism / splenectomy
Rx
Aim to keep Hct <0.45 to thrombosis
Aspirin 75mg OD Primary Myelofibrosis
Venesection if young Clonal proliferation of megakaryocytes PDGF
Hydroxycarbamide if older / higher risk Myelofibrosis
Extramedullary haematopoiesis: liver and spleen
Prognosis
Thrombosis and haemorrhage are main complications Features
30% MF Elderly
5% AML Massive HSM
Hypermetabolism: wt. loss, fever, night sweats
BM failure: anaemia, infections, bleeding
Polycythaemia Differential
Ix
True Polycythaemia: total volume of red cells Film: leukoerythroblastic
c teardrop poikilocytes
Primary: PV Cytopenias
Secondary BM: dry tap (need trephine biopsy)
Hypoxia: altitude, COPD, smoking 50% JAK2+ve
EPO: renal cysts/tumours
Rx
Pseudopolycythaemia: plasma volume Supportive: blood products
Acute Splenectomy
Dehydration Allogeneic BMT may be curative in younger pts.
Shock
Burns
Prognosis
Chronic 5yr median survival
Diuretics
Smoking

Acute Lymphoblastic Leukaemia Acute Myeloid Leukaemia
Children 2-5yrs (commonest childhood Ca) risk
c age: mean 65-70
Rare in adults Commonest acute leukaemia of adults
Aetiology Aetiology
Arrest of maturation and proliferation of lymphoblasts Neoplastic proliferation of myeloblasts
80% B lineage, 20% T lineage
Risk Factors
Risk Factors Chromosomal abnormalities
Genetic susceptibility (often Chr translocations) Radiation
Environmental trigger Downs
Radiation (e.g. during pregnancy) Chemotherapy: e.g. for lymphoma
Downs Myelodysplastic and myeloproliferative syndromes
Features FAB Classification (based on cell type)

M2: granulocyte maturation
BM Failure M3: acute promyelocytic leukaemia t(15;17)
Anaemia M4: acute myelomonocytic leukaemia
Thrombocytopenia bleeding M7: megakaryoblastic leukaemia trisomy 21
Leukopenia infection
Features
Infiltration
Lymphadenopathy BM Failure
Orchidomegaly Cytopenias
Thymic enlargement
HSM Infiltration
CNS: CN palsies, meningism Gum infiltration hypertrophy and bleeding (M4)
Bone pain HSM
Skin involvement
Ix Bone pain
WCC: lymphoblasts
RBC, PMN, plats Blood
BM aspirate DIC: APML (M3)
20% blasts Hyperviscosity: WCC may thrombi
Cytogenetic and molecular analysis
CXR+CT: mediastinal + abdominal LNs Ix
LP: CNS involvement WCC blasts (occasionally normal)
Anaemia and plats
Mx BM aspirate
20% blasts
Supportive Auer rods are diagnostic
Blood products
Allopurinol Dx
Hickman line or Portacath Made by immunological and molecular phenotyping
Flow cytometry
Infections Cytogenetic analysis affects Rx and guides prognosis
Gentamicin + tazocin
Prophylaxis: e.g. co-timoxazole, ciprofloxacin Mx
Chemotherapy (recruited into national trials) Supportive: as for ALL
1. Remission induction Infections: as for ALL
2. Consolidation + CNS Rx
3. Maintenance for 2-3yrs Chemotherapy
V. intensive long periods of neutropenia and plats
BMT
ATRA for APML
Best option for younger adults
BMT
Allogeneic if poor prognosis
Prognosis Destroy BM and leukemic cells c chemotherapy
85% survival in children and total body irradiation.
Worse in adults Repopulate marrow c HLA-matched donor HSCs
Autologous if intermediate prognosis
HSCs taken from pt.

Chronic Lymphocytic Leukaemia Chronic Myeloid Leukaemia
Commonest leukaemia in Western World 15% of leukaemia
M>F=2:1 Middle-aged: 60-60yrs
Elderly: 70s
Aetiology
Aetiology Myeloproliferative disorder: clonal proliferation of
Clone of mature B cells (memory cells) myeloid cells.
Features Features
Often asymptomatic incidental finding Systemic: wt. loss, fever, night sweats, lethargy
Symmetrical painless lymphadenopathy Massive HSM abdo discomfort
HSM Bruising / bleeding (platelet dysfunction)
Anaemia Gout
B symptoms: wt. loss, fever, night sweats Hyperviscosity
Complications Philadelphia Chromosome

Autoimmune haemolysis Reciprocal translocation: t(9;22)
Evans = AIHA and ITP Formation of BCR-ABL fusion gene
Infection (Ig): bacterial, zoster Constitutive tyrosine kinase activity
Marrow failure / infiltration Present in >80% of CML
Discovered by Nowell and Hungerford in 1960
Ix
WCC, lymphocytosis Ix
Smear cells WBC
se Ig PMN and basophils
+ve DAT Myelocytes
Rai or Binet staging Hb and plat (accelerated or blast phase)
urate
Dx BM cytogenetic analysis: Ph+ve
Immunophenotyping to distinguish from NHL
Natural Hx
Natural Hx Chronic phase: <5% blasts in blood or DM
Some remain stable for years Accelerated phase: 10-19% blasts
Nodes usually enlarge slowly ( lymphatic obstruction) Blast crisis: usually AML, 20% blasts
Death often due to infection: e.g. encapsulates, fungi
Richter Transformation: CLL large B cell lymphoma Rx
Imatinib: tyrosine kinase inhibitor
Rx >90% haematological response
Indications 80% 5ys
Symptomatic Allogeneic SCT
Ig genes un-mutated (bad prognostic indicator) Indicated if blast crisis or TK-refractory
17p deletions (bad prognostic indicator)
Supportive care
Chemotherapy
Cylophosphamide
Fludarabine
Rituximab
Radiotherapy
Relieve LN or splenomegaly
Prognosis
1/3 never progress
1/3 progress c time
1/3 are actively progressing

Non-Hodgkins Lymphoma Hodgkins Lymphoma
(80%) (20%)
Features Epidemiology
M>F=2:1 (esp. in paeds)
Lymphadenopathy: 75% @ presentation Bimodal age incidence: 20-29yrs and >60yrs
Painless May be assoc.
c EBV
Symmetric
Multiple sites Features
Spreads discontinuously
Lymphadenopathy
Extranodal Painless
Skin: esp. T cell lymphomas Asymmetric
CNS Spreads contiguously to adjacent LNs
Oropharynx and GIT Cervical nodes in 70% (also axillary and inguinal)
Splenomegaly May be alcohol-induced LN pain
Mediastinal LN may mass effects
B Symptoms SVC obstruction
Fever Bronchial obstruction
Night sweats
Wt. loss (>10% over 6mo) B Symptoms
Fever
Blood Night sweats
Pancytopenia Wt. loss (>10% over 6mo)
Hyperviscosity
Other
Ix Itch
FBC, U+E, LFT, LDH Pel Ebstein Fever: cyclical fever
LDH = worse prognosis Hepato- and/or spleno-megaly
Film
Normal or circulating lymphoma cells Ix
pancytopenias FBC, film, ESR, LFT, LDH, Ca
Classification: LN and BM biopsy ESR or Hb = worse prognosis
Staging: CT/MRI chest, abdomen, pelvis LN excision biopsy or FNA
Stage c Ann Arbor System Reed-Sternberg Cells (owls eye nucleus)
Staging: CT/MRI chest, abdomen, pelvis
Classification BM biopsy if B symptoms or Stage 3/4 disease
B Cell (commonest) Staging: Ann Arbor System

Low Grade: usually indolent but often incurable 1. Single LN region
Follicular 2. 2 nodal area on same side of diaphragm
Small cell lymphocytic (=CLL) 3. Nodes on both sides of diaphragm
Marginal Zone (inc. MALTomas) 4. Spread byond nodes: e.g. liver, BM
Lymphoplamsacytoid (e.g. Waldenstroms) + B if constitutional symptoms
High Grade: aggressive but may be curable
Diffuse large B cell (commonest NHL)
Burkitts Mx
Chemo, radio or both
T Cell
ABVD regimen
Adult T cell lymphoma: Caribs and Japs HTLV-1
BMT for relapse
Enteropathy-assoc. T cell lymphoma: chronic coeliac
Cutaneous T cell lymphoma: e.g. Sezary syn.
Anaplastic large cell
Prognosis
Depends on stage and grade
Mx 1A: >95% 5ys
Diagnosis and management in an MDT 4B: <40% 5ys
High Grade (e.g. DLBCL)
R-CHOP regimen
BMT for relapse
~30% 5ys
Low Grade (e.g. follicular)

Rx when clinically indicated (e.g. chloambucil)
>50% 5ys

Multiple Myeloma
Epidemiology Dx
M=F Clonal BM plasma cells 10%
Blacks>White=2:1 Presence of se and/or urinary monoclonal protein
~70yrs End-organ Damage: CRAB (1 or more)
Ca (>2.6mM)
Pathogenesis Renal insufficiency
Clonal proliferation of plasma cells monoclonal Ig Anaemia (<10g/dL)
Usually IgG or IgA Bone lesions
Clones may also produce free light chain ( or ): ~2/3
Excreted by kidney urinary BJP Mx
Light chains only seen in plasma in renal failure
Clones produce IL-6 which inhibits osteoblasts ( ALP) Supportive
and activates osteoclasts. Bone pain: Analgesia (avoid NSAIDs) +
bisphosphonates
Symptoms Anaemia: Transfusions and EPO
Renal impairment: ensure good hydration dialysis
Osteolytic Bone Lesions Infections: broad spectrum Abx IVIg if recurrent
Backache and bone pain
Pathological #s Complications
Vertebral collapse Ca: aggressive hydration, frusemide, bisphosphonates
Cord compression: MRI, dexamethasone + local radio
BM Infiltration Hyperviscosity: Plasmapheresis (remove light chains)
Anaemia, neutropenia or thrombocytopenia AKI: rehydration dialysis
Recurrent Bacterial Infections Specific

Neutropenia Fit pts.
Immunoparesis (= Ig) Induction chemo: lenalidomide + low-dose dex
Chemotherapy Then allogeneic BMT
Unfit pts.
Renal Impairment Chemo only: melphalan + pred + lenalidomide
Light chains Bortezomib for relapse
Ca
AL-amyloid Prognosis
Mean survival: 3-5yrs
Complications Poor prognostic indicators
Hypercalcaemia 2-microglobulin
Neurological: Ca, compression, amyloid albumin
AKI
Hyperviscosity
AL-amyloid (15%)
Ix
NB. Do ESR and Se electrophoresis if >50
c back pain
Bloods
FBC: normocytic normochromic anaemia
Film: rouleaux plasma cells cytopenias
ESR/PV, U+Cr, Ca, normal ALP
Se electrophoresis and 2-microglobulin
Urine
Stix: specific gravity (BJP doesnt show)
Electrophoresis: BJP
BM trephine biopsy
X-ray: Skeletal Survey

Punched-out lytic lesions
Pepper-pot skull
Vertebral collapse
Fractures

Other Paraproteinaemias Amyloidosis
Smouldering / Asymptomatic Myeloma Definition
Se monoclonal protein and/or BM plasma cells 10% Group of disorders characterised by extracellular
No CRAB deposits of a protein in an abnormal fibrillar form that is
resistant to degradation.
MGUS
Se monoclonal protein <30g/L
Clonal BM plasma cells <10% AL Amyloidosis
No CRAB Clonal proliferation of plasma cells
c production of
amyloidogenic light chains.
Solitary Plasmacytoma 1O: occult plasma cell proliferation
Solitary bone/soft tissue plasma cell lesion 2O: myeloma, Waldenstroms, MGUS, lymphoma
Se or urinary monoclonal protein
Normal BM and normal skeletal survey (except lesion) Features
No CRAB Renal: proteinuria and nephrotic syndrome
Heart: restrictive cardiomyopathy, arrhythmias, echo
Waldenstroms Macroglobulinaemia Sparkling appearance on echo
Lymphoplasmacytoid lymphoma monoclonal IgM Nerves: peripheral and autonomic neuropathy, carpal
band tunnel.
Features: GIT: macroglossia, malabsorption, perforation,
Hyperviscosity: CNS and ocular symptoms haemorrhage, hepatomegaly, obstruction.
Lymphadenopathy + splenomegaly Vascular: periorbital purpura (characteristic)
Ix: ESR, IgM paraprotein
Primary AL Amyloid AA Amyloidosis

Occult proliferation of plasma cells production of Amyloid derived from serum amyloid A
amyloidogenic monoclonal protein. SAA is an acute phase protein
Se or urinary light chains Chronic inflammation
RA
Paraproteinaemia in lymphoma or leukaemia IBD
E.g. seen in 5% of CLL Chronic infection: TB, bronchiectasis
Features
Renal: proteinuria and nephrotic syndrome
Hepatosplenomegaly
Familial Amyloidosis
Group of AD disorders caused by mutations in
transthyretin (produced by liver)
Features: sensory or autonomic neuropathy
Others: non-Systemic Amyloidosis

-amyloid: Alzheimers
2 microglobulin: chronic dialysis
Amylin: T2DM
Dx
Biopsy of affected tissue
Rectum or subcut fat is relatively non-invasive
Apple-green birefringence
c Congo Red stain under
polarized light.
Rx
AA amyloid may improve c underlying condition
AL amyloid may respond to therapy for myeloma
Liver Tx may be curative for familial amyloidosis
Prognosis
Median survival: 1-2yrs

Complications of Haematological Malignancies
Neutropenic Sepsis DIC
Widespread activation of coagulation from release of pro-
General Precautions coagulants into the circulation.
Barrier nursing in a side room Clotting factors and plats are consumed bleeding
Avoid IM injections (may infected haematoma) Fibrin strands haemolysis
Swabs + septic screen
TPR 4hrly Causes
Malignancy: e.g. APML
Antimicrobials Sepsis
Start broad spectrum Abx: check local guidelines Trauma
Consider G-CSF Obstetric events: e.g. PET
Signs
Hyperviscosity Syndrome Bruising
Bleeding
Causes Renal failure
RBC / Hct >0.5: e.g. PV
WCC > 100: e.g. leukaemia Ix
plasma proteins: Myeloma, Waldenstroms plats, Hb, APTT, PT, FDPs, fibrinogen (TT)
Features Rx
CNS: headache, confusion, seizures, faints Rx cause
Visual: retinopathy visual disturbance Replace: cryoprecipitate, FFP
Bleeding: mucus membranes, GI, GU Consider heparin and APC
Thrombosis
Ix Tumour Lysis Syndrome

plasma viscosity (PV) Massive cell destruction
FBC, film, clotting High count leukaemia or bulky lymphoma
Se + urinary protein electrophoresis K, urate renal failure
Prevention: fluid intake + allopurinol
Rx
Polycythaemia: venesection
Leukopheresis: leukaemia
Avoid transfusing before lowering WCC
Plasmapheresis: myeloma and Waldenstroms

Spleen and Splenectomy
Anatomy Splenectomy Hyposplenism
Intraperitoneal structure lying in the LUQ
Measures 1x3x5 inches Indications
Weighs ~7oz Trauma
Lies anterior to ribs 9-11 Rupture (e.g. EBV infection)
AIHA
Features ITP
1. Dull to percussion HS
2. Enlarges to RIF Hypersplenism
3. Moves inferiorly on respiration
4. Cant get above it Complications
5. Medial notch Redistributive thrombocytosis early VTE
Gastric dilatation (ileus)
Function: part of the mononuclear phagocytic system Left lower lobe atelectasis: v. common
Phagocytosis of old RBCs, WBCs and opsonised bugs susceptibility to infections
Antibody production Encapsulates: haemophilus, pneumo, meningo
Haematopoiesis
Sequestration of formed blood elements Film
Howell-Jolly bodies
Pappenheimer bodies
Causes of Massive Splenomegaly: >20cm Target cells
CML
Myelofibrosis Mx
Malaria Immunisation: pneumovax, HiB, Men C, yrly flu
LeishManiasis Daily Abx: Pen V or erythromycin
Gauchers (AR, glucocerebrosidase deficiency) Warning: Alert Card and/or Bracelet
Other Causes of Hyposplenism

SCD
All Causes of Splenomegaly Coeliac disease
Haematological IBD
Haemolysis: HS
Myelproliferative disease: CML, MF, PV
Leukaemia, lymphoma
Infective
EBV, CMV, hepatitis, HIV,
TB, infective endocarditis
Malaria, leishmanias, hydatid disease
Portal HTN: cirrhosis, Budd-Chiari
Connective tissue: RA, SLE, Sjogrens
Other
Sarcoid
Amyloidosis
Gauchers
O
1 Ab deficiency (e.g. CVID)
Splenomegaly may Hypersplenism

Pancytopenia as cells are sequestrated

The Lab
ESR The Peripheral Film
How far RBCs fall through anti-coagulated blood in 1h
Normal: ~20mm/h (M: age/2, F: (age+10)/2 Feature Causes
se proteins cover RBCs clumping rouleaux Acanthocytes Abetaliproteinaemia
faster settling ESR. Alcoholic lever disease
Basophilic stippling Lead poisoning
ESR Thalassaemia
Plasma factors Blasts Leukaemia
fibrinogen: inflammation Burr cels Uraemia
globulins: e.g. myeloma Dimorphic picture Myelodysplasia
Red cell factors Howell-Jolly bodies Hyposplenism
Anaemia ESR Heinz bodies G6PD deficiency
Irregularly contracted cells G6PD deficiency
of ESR >100 Leukoerythroblastic film BM infiltration
Myeloma Pappenheimer bodies Hyposplenism
SLE Pencil cells IDA
GCA Reticulocytes Haemolysis
AAA Haemorrhage
Ca prostate Spherocytes AIHA
Hereditary spherocytosis
Differential White Count Schistocytes MAHA
Prosthetic valve
Neutrophilia Target cells Hyposplenism
Bacterial infection Thalassaemia
Left shift Liver disease
Toxic granulation Tear-drop cells / Dacrocytes BM infiltration
Vacuolation
Stress: trauma, surgery, burns, haemorrhage
Steroids Cytochemistry
Inflammation: MI, PAN Myeloblasts
Myeloproliferative disorders: e.g. CML Sudan black B
MPO
Neutropenia Hairy cell leukaemia: tartrate resistant acid phosphatase
Viral infection Leukocyte alkaline phosphatase
Drugs: chemo, cytotoxics, carbimazole, sulphonamides : PV, ET, MF
Severe sepsis : CML, PNH
Hypersplenism: e.g. Feltys
Lymphocytosis
Viral infections: EBV, CMV
Chronic infections: TB, Brucella, Hepatitis, Toxo
Leukaemia, lymphoma: esp. CLL
Lymphopenia
Drugs: steroids, chemo
HIV
Monocytosis
Chronic infection: TB, Brucella, Typhoid
AML
Eosinophilia
Parasitic infection
Drug reactions: e.g.
c EM
Allergies: asthma, atopy, Churg-Strauss
Skin disease: eczema, psoriasis, pemphigus
Basophilia
Parasitic infection
IgE-mediated hypersensitivity: urticarial, asthma
CML

Infectious Disease
Contents
Tuberculosis .............................................................................................................................................................................. 138
Other Mycobacterial Disease .................................................................................................................................................... 139
Influenza .................................................................................................................................................................................... 139
HIV ............................................................................................................................................................................................. 140
Complications of HIV Infection .................................................................................................................................................. 141
Herpes Infections....................................................................................................................................................................... 142
Viral Hepatitis ............................................................................................................................................................................ 144
Gastrointestinal Infections 1 ...................................................................................................................................................... 145
Gastrointestinal Infections 2 ...................................................................................................................................................... 146
Sexually Transmitted Infections ................................................................................................................................................ 147
Syphilis ...................................................................................................................................................................................... 148
Zoonoses ................................................................................................................................................................................... 149
Malaria ....................................................................................................................................................................................... 150
Other Tropical Diseases ............................................................................................................................................................ 151
Miscellaneous Infections ........................................................................................................................................................... 152
Approach to Nosocomial Fever ................................................................................................................................................. 152

Tuberculosis
Pathophysiology Dx
Primary TB Latent TB
Childhood or nave TB infection Tuberculin Skin Test
Organism multiplies @ pleural surface Ghon Focus If +ve IGRA
Macros take TB to LNs
Nodes + lung lesion = Ghon complex Active TB
Mostly asympto: may fever and effusion CXR
Cell mediated immunity / DTH controls infection in 95% Mainly upper lobes.
Fibrosis of Ghon complex calcified nodule Consolidation, cavitation, fibrosis, calcification
(Ranke complex) If suggestive CXR take 3 sputum samples (one AM)
O
Rarely may 1 progressive TB (immunocomp) May use BAL if cant induce sputum
Microscopy for AFB: Ziehl-Neelsen stain
Primary Progressive TB Culture: Lowenstein-Jensen media (Gold stand)
Resembles acute bacterial pneumonia
Mid and lower zone consolidation, effusions, hilar LNs PCR
Lymphohaematogenous spread extra-pulmonary and Can Dx rifampicin resistance
milliary TB May be used for sterile specimens
Latent TB Tuberculin Skin Test

Infected but no clinical or x-ray signs of active TB Intradermal injection of purified protein derivative
Non-infectious Induration measured @ 48-72h
May persist for years Had BCG: +ve = 15mm
No BCG: +ve = 6mm
Weakened host resistance reactivation
False +ve: BCG, other mycobacteria, prev exposure
Secondary TB False ve: HIV, sarcoid, lymphoma
Usually reactivation of latent TB due to host immunity
Interferon Gamma Release Assays (IGRAs)
May be due to reinfection
Pt. lymphocytes incubated c M. tb specific antigens
Typically develops in the upper lobes
IFN- production if previous exposure.
Hypersensitivity tissue destruction cavitation and
formation of caseating granulomas. Will not be positive if just BCG (uses M. bovis)
E.g. Quantiferon Gold and T-spot-TB
Clinical Features
Pulmonary Mx
Cough, sputum Rx w/o culture if clinical picture is consistent
c TB
Malaise Continue even if culture results are negative
Fever, night sweats, wt. loss Stress importance of compliance
Haemoptysis Check FBC, liver and renal function
Pleurisy CrCl 10-50ml/min R dose by 50%, avoid E
Pleural effusion Test visual acuity and colour vision
Aspergilloma / mycetoma may form in TB cavities Give pyridoxine throughout Rx
Meningitis Initial Phase (RHZE): 2mos

Headache, drowsiness RMP: hepatitis, orange urine, enzyme induction
Fever INH: hepatitis, peripheral sensory neuropathy, PMN
Vomiting PZA: hepatitis, arthralgia (CI: gout, porphyria)
Meningism EMB: optic neuritis
Worsening over 1-3wks
CNS signs Continuation Phase (RH): 4mos
Papilloedema RMP
CN palsies INH
Lymph Nodes TB Meningitis

Cervical lymphadenitis: scrofula RHZE: 2mos
Painless neck mass: no signs of infection (cold) RH: 10mos
dexamethasone
GU TB
Frequency, dysuria, loin/back pain, haematuria Chemoprophylaxis in latent TB
Sterile pyuria RH for 3mo or H alone for 6mo
Bone TB: vertebral collapse and Potts vertebra

Skin: Lupus vulgaris (jelly-like nodules)
Peritoneal TB: abdominal pain, GI upset, ascites
Adrenal: Addisons disease
Other Mycobacterial Disease Influenza
Leprosy / Hansens Disease Pathophysiology
Spread: droplet
Pathogenesis Incubation: 1-4d
Transmitted via nasal secretions Infectivity: 1d before symptoms start to 7d after
Not very infectious Immunity: only strains which have already attacked pt
M. leprae
Presentation
Classification Fever
Tuberculoid Headache
Less severe Malaise
TH1-mediated control of bacteria paucibacillary
Myalgia
Anaesthetic hypopigmented macules
n/v
Lepromatous
Conjunctivitis
Weak TH1/2 multibacillary
Skin nodules
Nerve damage (esp. ulnar and peroneal) Complications
Bronchitis
Clinical Features Pneumonia: esp. Staph
Hypopigmented, insensate plaques Sinusitis
Trophic ulcers Encephalitis
Thickened nerves Pericarditis
Keratitis Reyes: rash, vomiting, LFTs in children give aspirin
Rx Ix
Tuberculoid: 6mo Rx Bloods: paired sera (takes 14d), lymphopenia,
Rifampicin monthly thrombocytopenia
Clofazamine daily Culture: 1wk from nasal swabs
Lepromatous: 2yrs PCR: takes 36h, 94% sensitivity, 100% specificity
Rifampicin monthly
Clofazamine + dapsone daily Rx
Bed rest + paracetamol
If severe
MAI Mx in ITU
Complicates HIV infection Cipro and co-amoxiclav: prevent Staph and Strep
Widely disseminated: lungs / GIT Oseltamivir
Fever, night sweats, wt. loss Neuraminidase inhibitor active vs. flu A and B
Diarrhoea May be indicated if >1yr c symptoms of <48hr
Hepatomegaly Zanamivir
Inhaled NA inhibitor active vs. influenza A and B
>5yrs
c symptoms <48h
Buruli Ulcer
M. ulcerans Prevention
Australia and the Tropics Good hygiene
Transmitted by insects Trivalent Vaccine
Nodule ulcer >65yrs
DM, COPD, heart, renal, liver failure
Immunosuppression: splenectomy, steroids
Medical staff
Fish Tank Granuloma Oseltamivir
M. marinum Prophylactic use if influenza A/B is circulating
Skin lesion appearing ~3wks after exposure and >1yr old and <48hr since exposure.

HIV
Immunology Ix
HIV binds via gp120 to CD4 HIV diagnostic tests
TH cells, monocytes, macrophages, neural cells Drug resistance studies
CD4+ cells migrate to lymphoid tissue where virus e.g. genotyping for reverse transcriptase or
replicates infection of new CD4+ cells protease mutations
Depletion and impaired function of CD4+ cells Mantoux test
immune dysfunction. Serology: toxo, CMV, HBV, HCV, syphilis
Monitoring
Virology CD4 count
RNA retrovirus Viral load (HIV RNA)
After entry, viral reverse transcriptase makes DNA FBC, U+E, LFTs, lipids, glucose
copy of viral RNA genome.
Viral integrase enzyme integrates this c host DNA
Core viral proteins synthesised by host and then HAART
cleaved by viral protease into mature subunits.
Completed virions released by budding Indications
CD4 350
AIDS-defining illness
Natural Hx Pregnancy
HIVAN
Acute Infection: usually asympto Co-infected
c HBV when Rx is indicated for HBV
Seroconversion Regimens
Transient illness 2-6wks after exposure 1 NNRTI + 2 NRTIs
Fever, malaise, myalgia, pharyngitis, macpap rash NNRTI = Efavirenz
Rarely meningoencephalitis NRTI = emtricitabine + tenofovir (Truvada)
Atripla = efavirenz + emtricitabine + tenofovir
Asymptomatic Infection PI + 2 NRTIs
But 30% will have PGL PI = lopinavir (+ low dose ritonavir = Kaletra)
Nodes >1cm in diameter
2 extra-inguinal sites Aim
3mo Undetectable VL after 4mo
If VL remains high despite good compliance
AIDS-related Complex (ARC) Change to a new drug combination
AIDS prodrome Request resistance studies
Constitutional symptoms: fever, night sweats, wt. loss
Minor opportunistic infections
Oral candida Prophylaxis
Oral hairy leukoplakia (EBV) CD4 <200: PCP co-trimoxazole
Recurrent HSV CD4 <100: Toxo co-trimoxazole
Seborrhoeic dermatitis CD4 <50: MAC azithromycin
AIDS
Defining illness
CD4 usually <200 HIV Exposure
Seroconversion post-needle-stick = ~0.3% (1/300)
Other Effects of HIV Report to occupational health
Osteoporosis Immunise against hep B (active + passive)
Dementia Test blood from both parties: HIV, HBC, HCV
Neuropathy Repeat recipient testing @ 3 and 6mo
Nephropathy
PEP
Start PEP in high-risk exposure from HIV+ or unknown
source.
Dx
Start ASAP as possible.
ELISA: detect serum (or salivary) anti-HIV Abs
Continue for at least 28d
Western Blot: for confirmation
E.g. Truvada + Kaletra
If recent exposure, may be window period
Usually 1-3wks
Can be 3-6mo
PCR: can detect HIV virions in the window period
Rapid Antibody Tests: false positives are a problem
and results should be confirmed by Western Blot

Complications of HIV Infection
Major AIDS-Defining Illnesses Candidiasis
Candidiasis: oesophageal or pulmonary Oral: nystatin suspension
Cryptococcal meningitis Oesophageal
Cryptosporidiosis Dysphagia
CMV retinitis Retrosternal pain
Kapsosi sarcoma Rx: itraconazole PO
Lymphoma: Burkitts, 1O brain
MAC
PCP Cryptococcal Meningitis
PML Presentation
Toxo Chronic Hx
TB Headache
Confusion
Papilloedema
CN lesions
TB and HIV
Ix
reactivation of latent TB
India ink CSF stain
risk of disseminated TB
CSF pressure
Higher bacterial loads but false ve smears CrAg in blood and CSF
Fewer bacteria in sputum
Rx
False ve skin tests (T cell anergy) Amphotericin B + flucytosine for 2wks then
Absence of characteristic granulomas fluconazole for for 6mo / until CD4 >200
toxicity combining anti-TB and anti-HIV drugs
IRIS: HAART CD4 paradoxical worsening of TB
symptoms PML
Progressive multifocal leukoencephalopathy
Demyelinating inflammation of brain white matter
PCP caused by JC virus.
P. jiroveci: fungus Presentation
Presentation Weakness
Dry cough Paralysis
Exertional dyspnoea Visual loss
Fever Cognitive decline
CXR: bilat perihilar interstitial shadowing Ix: JC viral PCR
Dx: visualisation from sputum, BAL or lung biopsy Rx: HAART, mefloquine may halt progression
Rx
High-dose co-trimoxazole IV
Or, pentamidine IVI Kaposis Sarcoma
Prednisolone if severe hypoxaemia
Neoplasm derived from capillary endothelial cells or
Prophylaxis fibrous tissue.
st
Co-trimoxazole if CD4 <200 or after 1 attack
Caused by HHV8 infection
Presentation
Purple papules
CMV May have visceral involvement
Mainly retinitis Rx
acuity HAART
Eye pain, photophobia Radiotherapy or chemotherapy
Pizza sign on Fundoscopy
Rx: ganciclovir eye implant
Also: pneumonitis, colitis, hepatitis
Other Presentations
Pulmonary
MAI
Toxoplasmosis Fungi: aspergillus, crypto, histoplasma
Presentation CMV
Posterior uveitis LFT and Hepatomegaly
Encephalitis Drugs
Focal neurology Viral hepatitis
Dx AIDS sclerosing cholangitis
Toxoplasma serology MAI
Toxo isoloation from LN or CNS biopsy Chronic Diarrhoea
CT/MRI: ring-shaped contrast enhancing lesions Bacteria: Salmonella, shigella, campylobacter
Rx: pyrimethamine + sulfadiazine + folate Protozoa: cryptosporidium, microsporidium
Prophylaxis Virus: CMV
Co-trimoxazole if CD4 <100 Neuro
O
Lifelong 2 prophylaxis CMV encephalitis
Alasdair Scott, 2012
Lymphoma 141
Herpes Infections
Herpes Simplex
Virology Disease Features Diagnosis Treatment
-neurotrophic Oropharyngeal / primary HSV-1 Topical Aciclovir
stomatitis Severe painful ulceration
Persists in DRG Fever + Submandibular lymphadenopathy
Encephalitis 90% HSV-1, 10% HSV-2 CSF: lympho, normal gluc Aciclovir IV
Mucocutaneous spread Flu-like prodrome CSF PCR
Headache, focal neuro, fits, odd behaviour, GCS MRI
Haemorrhagic necrosis of temporal lobes
Mollarets Meningitis HSV-2 mostly Aciclovir IV
Benign recurrent aseptic meningitis
Herpes Gladiatorum Rugby players, wrestlers Aciclovir PO
Painful vesicular rash, lymphadenopathy, fever
Herpetic Whitlow Healthcare workers, children Topical Aciclovir
Painful red finger
Eczema Herpeticum Herpes infection at the site of skin damage Aciclovir
Genital Herpes HSV-2 Urinary PCR Aciclovir PO
Flu-like prodrome
Dysuria, inguinal LNs, painful ulcers
Sacral radiculomyelitis urinary retention + sacral sensory
loss (Elsberg syndrome)
Herpes meningitis in 4-8% primary genital herpes
Herpetic Keratitis Unilat/bilat conjunctivitis + pre-auricular LNs
May cause a corneal ulcer = dendritic ulcer
Varicella Zoster
-neurotrophic Chickenpox Flu-like prodrome followed by vesicular rash that crops DIF of scrapings Calamine lotion
= varicella zoster Not contagious after lesions scab Aciclovir
Droplet or contact spread Droplet spread Tzanck cells - adults
- immunocomp
Replication in LN, then liver Complications: pneumonitis, haemorrhage, encephalitis - pregnant
and spleen - risk in immunocompromised and adults VZIg if contact
Shingles Zoster reactivation due to immunity/stress Aciclovir PO/IV
= herpes zoster Lifetime prevalence = 20% Famciclovir
Painful vesicular rash in dermatomal distribution Valaciclovir
- Thoracic and ophthalmic most commonly
- Multidermatomal / disseminated in immunocomp
Rx may progression to post-herpetic neuralgia
Post-Herpetic neuralgia = severe dermatomal pain

Ramsay Hunt = ear zoster, facial palsy, taste, hearing
EBV
-lymphotrophic Glandular fever Saliva or droplet spread Lymphocytosis
Infectious mononucleosis Fever, malaise, sore throat, cervical LNs +++ Atypical Lymphocytes
Infects B-cells Splenomegaly, hepatitis ( hepatomegaly and jaundice)
+ve Heterophile Abs
Complications: splenic rupture, CN lesion (e.g. 7), ataxia GBS, - Monospot
pancytopenia with megaloblastic marrow, meningoencephalitis, - Paul Bunnell
chronic fatigue
LFTs
Blood: serology, PCR
Burkitts lymphoma Jaw or abdo mass Starry-sky appearance
Endemic: Africa, malaria CD10, BCL6
Sporadic: non-African, impaired immunity t(8;14)
Immunodeficiency: HIV or post-Tx
PTLD Lymphoma following solid organ TX Viral load > 105c/ml Rituximab
Oral hairy leukoplakia HIV+ Aciclovir
Painless shaggy white plaque along lateral tongue border
Primary brain lymphoma HIV+ CT/MRI: Ring-enhancing lesion
Mass effects + systemic symptoms
Nasopharyngeal Ca Especially in Asia
False +ve Heterophile Abs: hepatitis, parvovirus, leukaemia, lymphoma, SLE, pancreatic Ca
CMV
-epitheliotropic Primary Infection 80% asymptomatic
Flu-like illness can occur (hepatitis)
Mucocutaneous spread Reactivation Immunocompromise Blood: PCR, serology 1 = Ganciclovir
2 = Foscarnet
Infected cells become swollen HIV: retinitis > colitis > CNS disease Owls Eye intranuclear 3 = Cidofovir
Transplant: pneumonitis > colitis > hepatitis> > retinitis inclusions
Atypical Lymphocytes
Congenital Petechiae at birth + hepatosplenomegaly
BMT Prevention
Do weekly PCR for first 100d
If viraemia +ve ganciclovir IV
Use CMV-ve irradiated blood products
Solid Organ Transplant Prevention

Greatest risk = seroneg recipient and seropos donor
Renal Tx prophylaxis = valganciclovir
Viral Hepatitis
Types Hep C
Mainly spread by blood.
Type Spread Cause Thousands of UK cases due to transfusion (eligible for
A FO Seafood, especially abroad compensation from Skipton fund)
B IV Blood, body fluids, babies (vertical)
C IV Mainly blood. Less vertical cf. HCV Presentation
D IV Dependent on prior HBV infection Initial infection is usually asymptomatic
E FO Developing world 25% have acute icteric phase
85% chronic infection
Hepatitis A 20-30% cirrhosis w/i 20yrs
risk of HCC
Presentation
Prodromal Phase Ix
Fever, malaise, arthralgia, nausea, anorexia Anti-HCV Abs
Distaste for cigarettes HCV-PCR
Icteric Phase Liver biopsy if PCR+ve to assess liver damage and
Jaundice, HSM, lymphadenopathy, cholestasis need for Rx
HCV genotype
Ix
ALT, AST (AST:ALT <2) Rx
IgM+ ~25d after exposure Indications
= recent infection Chronic haepatitis
IgG+ for life ALT
Fibrosis
Rx PEGinterferon 2b + ribavirin
Supportive efficacy if
Avoid alcohol Genotype 1, 4, 5 or 6
IFN- for fulminant hepatitis (rare) VL
Older
Prevention Black
Passive Ig <3mo protection (e.g. travellers) Male
Can give active vaccine
Hep D
Hep B Incomplete RNA virus that can only exist c HBV
risk of acute hepatic failure and cirrhosis
Incubation: 1-6mo Ix: anti-HDV Ab
Presentation Hep E
Prodromal phase and icteric phase as for Hep A Similar to HAV
Extra-hepatic features due to immune complexes Common in Indochina
Urticaria or vasculitic rash
Cryoglobulinaemia Differential
PAN
GN Acute
Arthritis Infection: CMV, EBV, leptospirosis
Toxin: EtOH, paracetamol, isoniazid, halothane
Ix Vasc: Budd-Chiari
HBsAg +ve = current infection Obs: eclampsia, acute fatty liver of pregnancy
+ve >6mo = chronic disease Other: Wilsons, AIH
HBeAg +ve = high infectivity
Anti-HBc IgM = recent infection Cirrhosis
Anti-HBc IgG = past infection Common:
Anti-HBs = cleared infection or vaccinated Chronic EtOH
HBV PCR: monitoring response to Rx NAFLD / NASH
Other:
Rx Genetic: Wilsons, 1ATD, HH, CF
Supportive AI: AH, PBC, PSC
Avoid EtOH Drugs: Methotrexate, amiodarone, isoniazid
Chronic disease: PEGinterferon 2b Neoplasm: HCC, mets
Vasc: Budd-Chiari, RHF, constrict. pericarditis
Complications
Fulminant hepatic failure (rare)
Chronic hepatitis (5-10%) cirrhosis in 5%
HCC

Gastrointestinal Infections 1
Organism Aetiology Inc Clinical Features Dx Mx
Staph aureus Meat 1-6h Diarrhoea, vomiting, abdo pain, BP
Rapid resolution
Bacilus cereus Reheated rice 1-6h Watery diarrhoea and vomiting
E. coli ETEC Travelling Watery diarrhoea Cipro
E. coli EHEC Undercooked minced beef 12-72h Dysentery Stool MC+S Dialysis if necessary
(O157:H7) - e.g. burgers HUS
Campylobacter Unpasteurised milk 2-5d Commonest bacterial diarrhoea Stool MC+S Cipro
jejuni Animal faeces (cats, dogs) Bloody diarrhoea, fever - 250-750mg BD PO
Guillain-Barre - 200-400mg BD IVI over 30min 1h
Reactive arthritis
Shigella 1-7d Bloody diarrhoea, abdo pain, fever Stool MC+S Cipro
Reactive arthritis
Salmonella Poultry, eggs, meat 12-48h Diarrhoea, vomiting, fever, abdo pain Cipro or ceftriaxone
enteritidis
Listeria Refrigerated food Watery diarrhoea, cramps, flu-like Blood culture Ampicillin
monocytogenes - cold enhancement Pneumonia
Pates, soft cheeses Meningoencephalitis
Miscarriage
Clostridium Antibiotic use 1-7d Bloody diarrhoea, abdo pain, fever Stool MC+S Stop causative Abx
difficle - cephs, cipro, clinda - foul smelling CDT ELISA 1st: Metronidazole 400mg TDS PO for 10d
Pseudomembranous colitis 2nd: Vanc 125mg QDS PO
FO spread Toxic megacolon Colectomy may be needed
Environment: spores GI perforation
Clostridium Canned / vac-packed food 12-36h Afebrile Toxin in blood samples Antitoxin
botulinum Kids=honey Descending symmetric flaccid paralysis Benpen + metro
Students=beans No sensory signs
Autonomic: dry mouth, fixed dilated pupils
Clostridium Reheated meat 8-24h Watery diarrhoea + cramps Stool MC+S Benpen + metro
perfringes
Vibrio cholera FO spread Hrs-5d Rice-water stools Stool MC+S Rehydrate
Dirty water Shock, acidosis, renal failure - Cooked rice powder solution
c K+ supplements
- Hartmanns
Cipro
Zn supplement
Vibrio Raw/undercooked seafood Profuse diarrhoea, abdo pain, vomiting Doxy 100-200mg/d PO
parahaemolyticus - Japan
Norovirus 12-48h Commonest cause in adults
50% of all gastroenteritis worldwide
Fever, diarrhoea, projectile vomiting
Rotavirus 1-7d Commonest cause in children
Secretory diarrhoea and vomiting

Gastrointestinal Infections 2
Organism Aetiology Inc Features Dx Mx
Salmonella FO spread 3-21d Malaise, headache, cough, constipation Leukopenia Cefotaxime or cipro
typhi/paratyphi Tropics High fever c relative bradycardia Blood culture
Rose spots: patchy red macules Urine or stool culture
Epistaxis, splenomegaly
Diarrhoea after 1st wk
Yersinia Food contaminated by 24-36h Abdo pain, fever, diarrhoea Serology Cipro
enterocolitica domestic animal faeces Mesenteric adenitis
Reactive arthritis, pharyngitis, pericarditis
Erythema Nodosum
Entamaeoba MSM 1-4wk Dysentery, wind, tenesmus Stool micro Metro
histolytica Travelling Wt. loss if chronic - Motile trophozoite
c 4 nuclei
Liver abscess Tinidazole if severe or
- RUQ pain, swinging fever, sweats Stool Ag abscess
- Mass in R lobe
Flask-shaped ulcer on histo
Giardia lamblia MSM 1-4wk Bloating, explosive diarrhoea, offensive gas Direct fluorescent Ab assay Tinidazole
Hikers Stool micro
Travellers Malabsorption steatorrhoea and wt. loss - Pear-shaped trophozoites
c2
nuceli
Duodenal fluid analysis on swallowed
string
Crypto parvum Waterborne 4-12d Severe acute watery diarrhoea in HIV Stool micro Paromomycin
- protozoan
Strongyloides Endemic in sub-tropics Migrating urticarial rash on trunk and legs Stool MC+S Ivermectin
stercoralis Hyperinfestation in AIDS Pneumonitis, enteritis Serology
Malabsorption chronic diarrhoea
Secretory Diarrhoea
Bacteria only found in lumen: dont activate innate immunity
No / low fever
No faecal leukocytes
Caused by bacterial toxins: Cholera, E. coli (except EIEC), S. aureus
Toxin cAMP open CFTR channel Cl loss followed by HCO3, Na and H2O loss secretory diarrhoea
Inflammatory Diarrhoea
Bacteria invade lamina propria: activate innate immunity
Fever
PMN in stool
Campylobacter, shigella, non-typhoidal salmonella, EIEC
Enteric Fever
Abdo pain, fever, mononuclear cells in stool
Typhoidal salmonella, Yersinia enterocolitica, Brucella

Sexually Transmitted Infections
Disease Risk Factors Clinical Features Diagnosis Management Complications
Gonorrhoea Young, Black M Men: Urine NAATs Cefixime PO Prostatitis
- Purulent urethral d/c, dysuria, prostatitis Ceftriaxone IM Epididymitis
Culture is gold standard Salpingitis / PID
Women: - Intracellular Gm- diplococci + Azithro for C Reactive Arthritis
- Usually asympto, dysuria, d/c - Transport in Stuarts Medium Ophthalmia neonatorum
Chlamydia 10% <25 Asympto in 50% men and 80% women NAATs Azithromycin / Prostatitis
- D-K Men: - Urine doxycycline Epididymitis
- Urethritis Salpingitis / PID
Culture Reactive Arthritis
Women: - Endocervical swab Opthalmia neonatorum
- Cervicitis, urethritis, salpingitis - Discharge
LGV Tropical STI Primary Stage: Chlamydia serovars L1, L2, L3 Azithromycin / Genital elephantiasis
Outbreak in MSM - painless genital ulcer, heals fast doxycycline Rectal strictures
- balanitis, proctitis, cervicitis NAATs
Inguinal Syndrome:
- Painful inguinal buboes
- Fever, malaise
gential elephantiasis
Anogenitorectal syndrome:
- Proctocolitis
Rectal strictures
Abscesses and fistulae
HPV 6, 11 Often asympto Podophyllotoxin
Cauliflower warts Cryotherapy
HSV 2 (/1) Flu-like prodrome PCR Analgesia Meningitis
Inguinal LNs Serology Aciclovir Elsberg Syndrome
Painful grouped vesicles ulcers - sacral radiculomyelitis
Dysuria retention + saddle
paraesthesia
Syphilis MSM Painless, indurated ulcer Dark ground microscopy Benzathine Pen Jarisch-Herxheimer Reaction
Mac pap rash: soles, palms RPR/VDRL: cardiolipin Abs - Hrs after 1st Pen dose
Aortic aneurysms - not treponeme specific - Fever, HR, vasodilation
Tabes dorsalis - indicate active disease
TPHA/FTA
- treponeme-specific
Chancroid Mainly Africa Papule Painful soft genital ulcer Culture Azithromycin
H. ducreyi - base covered in yellow/grey PCR
Progressing to inguinal buboes
Granuloma Africa Painless, beefy-red ulcer Donovan bodies Erythromycin
inguinale India Subcutaneous inguinal granulomas - Giemsa stain
(Donovanosis) - Pseudobuboes
Klebsiella Possible elephantiasis
granulomatis
Syphilis
Stages Dx
Stage Features: due to endarteritis obliterans Cardiolipin antibody

Primary Macpapindurated, painless ulcer = Chancre E.g. VDRL, RPR
Regional LNs Not treponeme specific
Heals in 1-3wks False +ve: pregnancy, pneumonia, SLE,
malaria, TB
Secondary 6wks -6mo wks after chancre +ve in 1O and 2O syphilis (wanes in late disease)
Systemic bacteraemia fever, malaise Reflects disease activity: -ve after Rx
Skin rash:
Treponeme-specific Ab
Symmetrical, non-itchy, mac pap / pustular
Palms, soles, face, trunk +ve in 1O and 2O syphilis
Buccal snail-track ulcers Remains +ve despite Rx
Warty lesions: condylomata lata THPA and FTA
Treponemes
Tertiary 2-20yrs latency
Seen by dark ground microscopy of chancre fluid
Gummas
Granulomas in skin, mucosa, bones, joints Seen in lesions of 2O syphilis
May not be seen in late syphilis
Quaternary Syphilitic aortitis
Aortic aneurysm
Aortic regurg Rx
Neurosyphilis 2-3 doses (1wk apart of benzathine penicillin
Paralytic dementia Or, doxycycline for 28d
Meningovascular: CN palsies, stroke
Tabes dorsalis Jarisch-Herxheimer Reaction
Degeneration of sensory neurones, Fever, HR, vasodilatation hrs after first Rx
esp. legs ? sudden release of endotoxin
Ataxia and +ve Rombergs Rx: steroids
Areflexia
Plantars
Charcots joints
Argyll-Robertson pupil
accommodates, doesnt react

Zoonoses
Disease Risk Factors Presentation Diagnosis Management
Leptospirosis Infected rat urine High fever, headache, myalgia / myositis Blood culture Doxycycline
Weils Disease - swimming Cough, chest pain haemoptysis Serology
- canoeing hepatitis
c jaundice
meningitis
Brucellosis Middle and Far East, Malta Undulant fever (PUO): peak PM, normal AM Pancytopenia Doxy + RMP + gent
Melitensis Unpasteurised milk / cheeses Sweats, malaise, anorexia Positive Rose Bengal Test
- goats, commonest - esp. goat Arthritis, spinal tenderness Anti-O-polysaccharide Ag
Abortus: cattle LN, HSM
Suis: pigs Vets, farmers, abattoir workers Rash, jaundice
Lyme disease Ixodes tick bite Early localised: Biopsy ECM edge + Ab Rash: Doxy
Walkers, hikers - Erythema migrans (target lesions) ELISA
Borrelia burgdorferi Early disseminated: Complications: IV benpen
- Malaise, LN, migratory arthritis, hepatitis
Late persistent :
- Arthritis, focal neuro (Bells palsy), heart block,
myocarditis
- Lymphocytoma: blue/red ear lobe
Cat-Scratch Disease Hx of cat scratch Tender regional LNs +ve cat scratch skin Ag test Azithro
Bartonella henselae
Toxoplasmosis Cats are definitive hosts Mostly asympto CT/MRI: ring-shaped Pyrimethamine + sulfadiazine
Sheep / pig intermediate hosts Reactivated in immunodeficiency contrast enhancing CNS
- Encephalitis: confusion, seizures, focal lesions Septrin prohylaxis in HIV
- SOL/ICP
- Posterior uveitis Serology
Rabies Animal bites Prodrome Bullet-shaped RNA virus Immunised
- Bats, dogs, foxes - Headache, malaise, bite - diploid vaccine
itch, odd behaviour Negri bodies
Furious Rabies Unimmunised
- Hydrophobia - vaccine + rabies Ig
- Muscle spasms
Dumb Rabies
- flaccid limb paralysis
Anthrax Spread by infected carcasses or hides Cutaneous Microscopy Cipro + clindamycin
- abattoir workers, farmers - ulcer with BLACK centre - Gm+ spore forming rod
- rim of oedema
Inhalational
- massive lymphadenopathy
- mediastinal haemorrhage
- resp failure
GI
- severe bloody diarrhoea

Malaria
Species
Species Inc Liver stage? Rhythm Rx
Falciparum 7-10d No Tertian: 48h Artemether-lumefantrine (Riamet)
(Quinine + Doxy)
Vivax 10-17d Chronic liver stage Tertian: 48h Chloroquine then primaquine
Ovale 10-17d Chronic liver stage Tertian: 48h Chloroquine then primaquine
Malariae 18-40d No Quartan: 72h Chloroquine then primaquine
Biology Mx
Plasmodium sporozoites injected by females Anopheles
mosquito. Uncomplicated Ovale, Vivax, Malariae
Sporozoites migrate to liver, infect hepatocytes and multiply Chloroquine base
asymptomatically (incubation period) merozoites Then primaquine
Merozoites released from liver and infect RBCs
Multiply in RBCs Uncomplicated Falciparum
Haemolysis Artemether-lumefantrine
RBC sequestration splenomegaly
Cytokine release Severe Falciparum Malaria
Need ITU Mx
IV antimalarials
Falciparum Malaria Prophylaxis
90% present w/i 1mo
No resistance: proguanil + chloroquine
Resistance: mefloquine or malarone
Flu-like Prodrome
Malarone: atovaquone + proguanil
Headache, malaise, myalgia, anorexia
Fever Paroxysms
Shivering 1h Antimalarial SEs
Hot stage for 2-6h: ~41OC Chloroquine: retinopathy
Flushed, dry skin, headache, n/v Fansidar: SJS, LFTs, blood dyscrasias
Sweating for 2-4h as temp falls Primaquine: haemolysis if G6PD deficient
Malarone: abdo pain, nausea, headache
Signs Mefloquine: dysphoria, neuropsychiatric signs
Anaemia
Jaundice
HSM
No rash, no LNs
Complications
Cerebral malaria: confusion, coma, fits
Lactic acidosis Kussmaul respiration
Hypoglycaemia
O
Acute renal failure: 2 to ATN
ARDS
Dx
Serial thick and thin blood films
Parasitaemia level
FBC: anaemia, thrombocytopenia
Clotting: DIC
Glucose
ABG: lactic acidosis
U+E: renal failure
Urinalysis: haemoglobionuria

Other Tropical Diseases
Disease Aetiolgy Presentation Diagnosis
African Tsetse fly Tender subcut nodule @ site of infection Thick and thin films
Trypanosomiasis - flagellated protozoa
Haemolymphatic Stage
Sleeping sickness - rash, fever, rigors, headaches Serology
- LNs and HSM
- Posterior cervical nodes (Winterbottoms sign)
Miningoencephalitic Stage
- Wks Mos after original infection
- Convulsions, agitation confusion
- Apathy, depression, hypersomnolence, coma
T. gambiense: West Africa

T. rhodesiense: East Africa
- More severe than gambiense
American Reduviids T. cruzi
Trypanosomiasis - Latin America
- Erythematous nodule, fever, LN, HSM
Chagas Disease - Swelling of eyelid (Romanas Sign)
- Cardiac disease
Leishmaniasis Sandflies Cutaneous (L. major, L. tropica) Visceral:
- Skin ulcer @ bite depigmented scar - Leucopaenia
South + Central Am Diffuse cutaneous - Ig
Asia - Widespread nodules (fail to ulcerate) - Pancytopaenia
Africa - Serology
Mucocutaneous (L. braziliensis)
- South America Visualisation of
- Ulcer in mucous mems of mouth and nose Leishman-Donovan
bodies
Visceral = Kala Azar (L. donovani)
- Dry, warty hyperpigmented skin lesions
(dark face and hands)
- Prolonged fever
- Massive splenomegaly, LNs, abdo pain
Filariasis Asia Lymphatic Filariasis Nemotodes
Africa - Wuchereria bancrofti
South America - elephantiasis Microfilariae in the blood
Eosinophilia
Dengue Fever Aedes mosquito Flushes: facem neck, chest Serology
Central macpap rash Tourniquet test
RNA virus South + Central Am Headache, arthralgia
Asia HSM
Africa Jaundice
Haemorrhage: petechial, GI, gums or nose, GU
NB. can exclude if fever starts >2wks after

leaving endemic area.
Schistosomiasis Tremotode (Fluke) Itchy papular rash at site of penetration
Snail vector - Swimmers Itch
Mansoni
- abdo pain D&V
- later hepatic fibrosis and portal HTN
- HSM
Haematobium
- frequency, dysuria, haematuria
- may hydronephrosis and renal failure
- risk of bladder SCC

Miscellaneous Infections Approach to Nosocomial Fever
Tetanus Epidemiology
2-30% of hospital inpatients
Pathophysiology Mostly due to bacterial infection
Clostridium tetani spores live in faeces, dust, soil and
medical instruments. Definition
Mucosal breach admits spores Oral temp 38 that occurs 48hrs after admission and
Spores germinate and produce exotoxin is recorded on at least two separate occasions over 48h
Exotoxin prevents the release of inhibitory transmitters
GABA and glycine Causes
generalised muscle over-activity Infection (commonest cause)
Inflammation
Presentation Ischaemia
Prodrome: fever, malaise, headache Malignancy
Trismus Drug-induced
Risus sardonicus
Opisthotonus Mx
Spasms: may respiratory arrest
Careful Hx and examination
Autonomic dysfunction: arrhythmias, fluctuating BP
Study drug list
Basic Ix
Rx
Urinalysis
Mx on ITU: may need intubation
FBC, LFT, ESR, cultures
Human tetanus Ig Swabs
Metronidazole, benpen CXR
Prevention
Active immunisation
c tetanus toxoid
Clean minor wounds
Uncertain Hx / <3 doses: give vaccine
3 doses: only vaccinate if >10yrs since last dose
Heavily contaminated wounds
Uncertain Hx / <3 doses: vaccine + TIg
3 doses: vaccinate if 5yrs since last dose
Actinomycosis
Actinomyces israelii
Subcut infections: esp. on jaw
Forms sinuses which discharge pus containing sulphur
granules.
Rx: ampicillin for 30d, then pen V for 100d

Neurology
Contents
Basic Neuroscience ................................................................................................................................................................... 155
Motor and Sensory Patterns...................................................................................................................................................... 158
Specific Neurological Patterns and Causes .............................................................................................................................. 159
Muscle Weakness Differential ................................................................................................................................................... 160
Hand Wasting Differential .......................................................................................................................................................... 160
Gait Disturbance Differential ..................................................................................................................................................... 160
Blackouts ................................................................................................................................................................................... 161
Vertigo and Dizziness ................................................................................................................................................................ 162
Causes of Hearing Loss ............................................................................................................................................................ 162
Abnormal Involuntary Movements Dyskinesias ..................................................................................................................... 163
Dementia ................................................................................................................................................................................... 164
Delirium / ACS ........................................................................................................................................................................... 164
Headache: Differential and Investigation .................................................................................................................................. 165
Headaches: Key Features ......................................................................................................................................................... 166
Migraine ..................................................................................................................................................................................... 167
Subarachnoid Haemorrhage ..................................................................................................................................................... 168
Stroke: Causes and Investigation.............................................................................................................................................. 169
Stroke: Presentation .................................................................................................................................................................. 170
Stroke: Management ................................................................................................................................................................. 171
Transient Ischaemic Attack ....................................................................................................................................................... 172
Subdural Haemorrhage ............................................................................................................................................................. 173
Extradural Haemorrhage ........................................................................................................................................................... 173
Intracranial Venous Thrombosis................................................................................................................................................ 174
Meningitis .................................................................................................................................................................................. 175
Encephalitis ............................................................................................................................................................................... 176
Cerebral Abscess ...................................................................................................................................................................... 176
Epilepsy: Features ..................................................................................................................................................................... 177
Epilepsy: Investigation and Management ................................................................................................................................. 178
Status Epilepticus ...................................................................................................................................................................... 179
Head Injury ................................................................................................................................................................................ 180
Space Occupying Lesions ......................................................................................................................................................... 181
Idiopathic Intracranial Hypertension .......................................................................................................................................... 181
Raised ICP ................................................................................................................................................................................ 182
Signs and Symptoms ................................................................................................................................................................ 182
Parkinsonism ............................................................................................................................................................................. 183
Parkinsons Disease .................................................................................................................................................................. 184
Multiple Sclerosis....................................................................................................................................................................... 185
Cord Compression..................................................................................................................................................................... 186
Cervical and Lumbar Degeneration........................................................................................................................................... 187
Facial Nerve Palsy..................................................................................................................................................................... 188
Mononeuropathies ..................................................................................................................................................................... 189
Polyneuropathies ....................................................................................................................................................................... 190
Autonomic Neuropathy .............................................................................................................................................................. 190
Guillain-Barr Syndrome ...........................................................................................................................................................
191
Charcot-Marie-Tooth Syndrome ................................................................................................................................................ 191
Motor Neurone Disease ............................................................................................................................................................ 192
Polio ........................................................................................................................................................................................... 192
Myopathies ................................................................................................................................................................................ 193
Myasthenia Gravis ..................................................................................................................................................................... 194
Lambert-Eaton Myasthenic Syndrome (LEMS)......................................................................................................................... 194
Botulism ..................................................................................................................................................................................... 194
Neurofibromatosis 1 von Recklinghausens ........................................................................................................................... 195
Neurofibromatosis 2 .................................................................................................................................................................. 195
Intrinsic Cord Disease ............................................................................................................................................................... 196
Syringomyelia ............................................................................................................................................................................ 196
Brown-Sequard Syndrome ........................................................................................................................................................ 196
Miscellaneous Conditions .......................................................................................................................................................... 197

Basic Neuroscience
The Spinal Cord Cerebellum and Basal Ganglia
Output to cortex via thalamus
Gross Anatomy Regulation of posture, locomotion, coordination and
Foramen magnum to L1 movement.
Terminates as conus medullaris
Spinal nerves continue inferiorly as corda equina
Denticulate ligament and filum terminale are pial Internal Capsule
extensions that suspend cord in subarachnoid space. White matter carrying axonal fibres from motor cortex to
pyramids of medulla.
Infarction contralateral hemiparesis
Blood Supply
3 longitudinal vessels
2 posterior spinal arteries: dorsal 1/3
1 anterior spinal artery: ventral 2/3 Brain Lobar Function
Reinforced by segmental feeder arteries
E.g. artery of Adamkiewicz Frontal
Longitudinal veins drain into extradural vertebral plexus Cognition and memory
Executive function
Motor cortex
Organisation Dominant hemisphere: motor speech (Brocas area)
Parietal
Sensory cortex
Body orientation
Temporal
Memory
Dom hemisphere: receptive language (Wernickes)
Occipital
Visual cortex
Homunculus
Dorsal Columns (FG + FC)

Mode: fine touch, vibration and proprioception
Cell body: DRG
Decussation: in medulla forming medial lemniscus
Lateral Spinothalamic Tract

Mode: pain and temperature
Cell body: DRG
Decussation: in cord, at entry level
Lateral Corticospinal Tract

Mode: motor (body)
O
Cell body: 1 motor cortex Brain Blood Supply
Decussation: pyramidal decussation in ventral medulla
Thalamic Nucelei
VPL: somoatosensory body
VPM: somatosensory head
LGN: visual
MGN: auditory

Long Tracts Cranial Nerve Nuclei
Motor Pathway
Sensory Pathway

NMJ Vestibulo-occular Pathways
Transmission Vestibulo-occular reflex (VOR)
1. Presynaptic voltage-gated Ca2+ channels open Ca2+ Axons from vestibular neurones project via MLF to
influx abducens and occulomotor nuclei
2. ACh vesicles released from presynaptic terminal Head turns L eyes turn R
3. ACh diffuses across cleft Absent Dolls Eye sign = brainstem death
4. ACh binds to nicotinic receptors on post-synaptic
terminal Caloric Tests
5. Na+ influx depolarisation Ca2+ release from SR Warm firing of vestibular N. eyes turn to
muscle contraction contralateral side
c nystagmus to ipsilateral side
6. ACh is degraded by acetylcholinesterase and choline is Remember fast direction of nystagmus COWS
taken up into presynaptic terminal. Cold: Opposite
Warm: Same
Blockade Absence of eye movements = brainstem damage on
1. Block presynaptic choline uptake: hemicholinium
side being tested.
2. Block ACh vesicle fusion: botulinum, LEMS
3. Block nicotinic ACh receptors
Non-depolarising: atracurium, vecuronium Visual Field Defects
Depolarising: suxamethonium
Dopamine Pathways
Mesocorticolimbic: SCZ
Nigrostriatal: Parkinsonism
Tuberoinfundibular: Hyperprolactinaemia
Sympathetic NS
Cell bodies from T1-L2
GVE preganglionic fibres synapse @ either:
Paravertebral ganglia
Prevertebral ganglia
Chromaffin cells of adrenal medulla
Preganglionic fibres are myelinated and release ACh @
nicotinic receptors Pupillary Light Reflex
Postganglionic fibres are unmyelinated and release NA
@ adrenergic receptors
Except @ sweat glands where they release ACh
for muscarinic receptors.
Parasympathetic NS
Cranial: CN 3, 7, 9, 10
Ciliary: ciliary muscle and sphincter pupillae
Pterygopalatine: mucus mems of nose and
palate, lacrimal gland
Submandibular: submandibular and sublingual
glands
Otic: parotid gland
Vagus supplies thoracic and abdo viscera
Sacral: pelvic splanchnic nerves (S2-4) innervate pelvic
viscera
Preganglionic fibres release ACh @ nicotinic receptors
Postganglionic fibres release ACh @ muscarinic
receptors
CN Nuclei
Midbrain: 3, 4, (5)
Pons: 5, 6, 7, 8
Medulla: (5), 9, 10, 11, 12
NB. All nuclei except 4, innervate ipsilateral side. Fibres from

trochlear nucleus decussate in medulla and supply
contralateral SOB muscle.

Motor and Sensory Patterns
Patterns of Motor Deficits
Cortical Lesions
Hyperreflexia proximally in arm or leg
Unexpected patterns: e.g. all movements in hand/foot
Internal Capsule and Corticospinal Lesions

Contralateral hemiparesis c pyramidal distribution.
Lesion c epilepsy, cognition or homonymous hemianopia = in a cerebral hemisphere
Lesion c contralateral CN palsy = brainstem lesion on the side of the palsy (E.g. Miilard-Gubler syn.)
Cord Lesions
Quadriparesis / paraparesis
Motor and reflex level: LMN signs at level of lesion and UMN signs below
Peripheral Neuropathies
Usually distal weakness
In GBS weakness is proximal (root involvement)
Single nerve = mononeuropathy: trauma or entrapment
Several nerves = mononeuritis multiplex: vasculitis or DM
UMN Lesions LMN Lesions

Motor cells in pre-central gyrus to anterior horn cells Anterior horn cells to peripheral nerves
in the cord Wasting
Pyramidal weakness: extensors in UL, flexors in LL Fasciculation
No wasting Flaccidity: tone
Spasticity: tone clonus Hyporeflexia
Hyperreflexia Down-going plantars
Up-going plantars
Primary Muscle Lesions

Symmetrical loss
Reflexes lost later vs. neuropathies
No sensory loss
Fatiguability in myasthenia
Patterns of Sensory Deficits

Pain and temp travel in small fibres in peripheral
nerves and in anterolateral spinothalamic tracts
Touch, joint position and vibrations travel in large
fibres peripherally and in dorsal columns centrally
Distal Sensory Loss

Suggests a neuropathy
Sensory Level
Hallmark of cord lesion
Hemi-cord lesion Brown-Sequard syndrome
Ipsilateral loss of proprioception / vibration and
UMN weakness with contralateral loss of pain
Dissociated Sensory Loss

Selective loss of pain and temp c conservation of
proprioception and vibration
Occurs in cervical cord lesions: e.g. syringomyelia

Specific Neurological Patterns and Causes
Cerebellar Syndrome Vertebrobasilar Circulation
Effects: DANISH Supplies cerebellum, brainstem and occipital lobes
Dysdiadochokinesia Combination of symptoms
Dysmetria: past-pointing Visual: hemianopia, cortical blindness
Ataxia: limb / trunkal Cerebellar: DANISH
Nystagmus: horizontal = ipsilateral hemisphere CN lesions
Intention tremor Hemi- / quadriplegia
Speech: slurred, staccato, scanning dysarthria Uni- / bi-lateral sensory symptoms
Hypotonia
Common Causes: PASTRIES Lateral Medullary Syn. / Wallenbergs Syn.

Paraneoplastic: e.g. from bronchial Ca Occlusion of one vertebral A. or PICA
Alcohol: thiamine and B12 deficiency Features: DANVAH
Sclerosis Dysphagia
Tumor: e.g. CPA lesion Ataxia (ipsilateral)
Rare: MSA, Friedrichs, Ataxia Telangiectasia Nystagmus (ipsilateral)
Iatrogenic: phenytoin Vertigo
Endo: hypothyroidism Anaesthesia
Stroke: vertebrobasilar Ipsilat facial numbness + absent corneal
reflex
Contralateral pain loss
Horners syndrome (ipsilateral)
Anterior Cerebral Artery
Supplies frontal and medial part of cerebrum
Contralateral motor / sensory loss in the legs > arms Millard-Gubler Syndrome: crossed hemiplegia
Face is spared Pontine lesions (e.g. infarct)
Abulia (pathological laziness) Effects: 6th and 7th CN palsy + contralateral hemiplegia
Middle Cerebral Artery Locked-in Syndrome

Supplies lateral / external part of hemisphere Pt. is aware and cognitively intact but completely
Contralateral motor / sensory loss in face and arms > paralysed except for the eye muscles.
legs. Causes
Contralateral homonymous hemianopia due to Ventral pons infarction: basilar artery
involvement of optic radiation Central potine myelinolysis: rapid correction of
Cognitive changes hyponatraemia
Dominant (L): aphasia
Non-dominant (R): neglect, apraxia Cerebellopontine Angle Syndrome
Causes: acoustic neuroma, meningioma, cerebellar
astrocytoma, metastasis (e.g. breast)
Posterior Cerebral Artery Effects: ipsilat CN 5, 6, 7, 8 palsies + cerebellar signs
Supplies occipital lobe Absent corneal reflex
Contralateral homonymous hemianopia
c macula LMN facial palsy
sparing. LR palsy
Sensorineural deafness, vertigo, tinnitus
DANISH
Subclavian Steal Syndrome

Subclavian A. stenosis proximal to origin of vertebral A.
may blood being stolen from this vertebral artery by
retrograde flow.
Syncope / presyncope or focal neurology on using the
arm.
BP difference of >20mmHg between arms
Anterior Spinal Artery / Becks Syndrome

Infarction of spinal cord in distribution of anterior spinal
artery: ventral 2/3 or cord.
Causes: Aortic aneurysm dissection or repair
Effects
Para- / quadri-paresis
Impaired pain and temperature sensation
Preserved touch and proprioception
Muscle Weakness Differential Hand Wasting Differential
1. Cerebrum / Brainstem 1. Cord
Vascular: infarct, haemorrhage Anterior Horn: MND, polio
Inflammation: MS Syringomyelia
SOL
Infection: encephalitis, abscess 2. Roots (C8 T1)
Compression: spondylosis, neurofibroma
2. Cord
Vascular: anterior spinal artery infarction 3. Brachial Plexus
Inflammation: MS Compression
Injury Cervical rib
Tumour: Pancoasts, breast
3. Anterior Horn Avulsion: Klumpkes palsy
MND, polio
4. Neuropathy
4. Roots / Plexus Generalised: CMT
Spondylosis Mononeuritis multiplex: DM
Cauda equina syndrome Compressive mononeuropathy
Carcinoma Median: thenar wasting
Ulnar: hypothenar and interossei wasting
5. Motor Nerves
Mononeuropathy: e.g. compression 5. Muscle
Polyneuropathy: e.g. GBS, CMT Disuse: RA
Compartment syndrome: Volkmans ischaemic
6. NMJ contracture
GB, LEMS, botulism Distal myopathy: myotonic dystophy
Cachexia
7. Muscle
Toxins: steroids
Poly- / Dermato-myositis
Inherited: DMD, BMD, FSH
Gait Disturbance Differential

Motor Sensory
Basal Ganglia: festinating / shuffling Vestibular (Rombergs +ve)

PD Menieres
Parkinsonism: MSA, PSP, Lewy body dementia, CBD Viral labyrinthitis
Brainstem lesion
UMN Bilateral: spastic, scissoring
Cord: compression, trauma, hereditary spastic Cerebellar: ataxic
paraparesis, syringomyelia, transverse myelitis EtOH
Bihemispheric: CP, MS Infarct
UMN Unilateral: spastic circumducting Proprioceptive Loss (Rombergs +ve)

Hemisphere lesion: CVS, MS, SOL Dorsal columns: B12 deficiency
Hemicord: MS, tumour Peripheral neuropathy: DM, EtOH, uraemia
LMN Bilateral: bilat foot drop Visual Loss

Polyneuropathy: CMT, GBS
Corda equina
Other
LMN Unilateral: foot drop high stepping gait Myopathy, MG/LEMS
Ant horn: polio Medical: postural hypotension, Stokes-Adams, arthritis
Radicular: L5 root lesion
Sciatic / common peroneal nerve: trauma, DM
Mixed UMN and LMN: MAST

MND
Ataxia: Friedrichs
SACD
Taboparesis
Blackouts
Causes: CRASH Presentation and Investigation
Cardiac: Stokes-Adams Attacks Cardiogenic Syncope
Brady: heart block, sick sinus, long-QT Trigger: exertion, drug, unknown
Tachy: SVT, VT Before: palpitations, chest pain, dyspnoea
Structural During: pale, slow/absent pulse, clonic jerks may occur
Weak heart: LVF, tamponade After: rapid recovery
Block: AS, HOCM, PE Ix: ECG, 24hr ECG, Echo
Reflexes
1. Vagal overactivity Reflex: Vasovagal
Vasovagal syncope Trigger: prolonged standing, heat, fatigue, stress
Situational: cough, effort, micturition Before
Carotid sinus syncope Gradual onset: secsmins
Nausea, pallor, sweating, tunnel vision, tinnitus
2. Sympathetic underactivity = Post. Hypotension Cannot occur lying down
Salt deficiency: hypovolaemia, Addisons During
Toxins Pale, grey, clammy, brady
Cardiac: ACEi, diuretics, nitrates, -B Clonic jerks and incontinence can occur, but no
Neuro: TCAs, benzos, antipsychotics, L- tongue biting
DOPA After: rapid recovery
Autonomic Neuropathy: DM, Parkinsons, GBS Ix: Tilt-table testing
Dialysis
Unwell: chronic bed-rest
Pooling, venous: varicose veins, prolonged Reflex: Postural Hypotension
standing Trigger: Standing up
Before, During and After as for vagal above
Arterial Ix: Tilt-table testing
Vertebrobasilar insufficiency: migraine, TIA, CVA,
subclavian steal
Shock Arterial
Hypertension: phaeochromocytoma Trigger: Arm elevation (subclavian steal), migraine
Before, During and After as for vasovagal brainstem
Systemic Sx (diplopia, nausea, dysarthria)
Metabolic: glucose Ix: MRA, duplex vertebrobasilar circulation
Resp: hypoxia, hypercapnoea (e.g. anxiety)
Blood: anaemia, hyperviscosity
Systemic
Head Hypoglycaemia: tremor, hunger, sweating, light-
Epilepsy headedness LOC
Drop attacks
Head: Epileptic
Trigger: flashing lights, fatigue, fasting
Examination Before: e.g. aura in complex partial seizures feeling
Postural hypotension: difference of >20/10 after strange, epigastric rising, deja/jamias vu, smells, lights,
standing for 3min vs. lying down automatisms
Cardiovascular During: Tongue biting, incontinence, stiffnessjerking,
Neurological eyes open, cyanosis, SpO2
After: headache, confusion, sleeps, Todds palsy
Ix: EEG, se prolactin at 10-20min
Ix
ECG 24hr ECG Head: Drop Attacks
U+E, FBC, Glucose Trigger: nil
Tilt table Before: no warning
EEG, sleep EEG During: sudden weakness of legs causes older woman
Echo, CT, MRI brain to fall to the ground.
After: no post-ictal phase

Vertigo and Dizziness Causes of Hearing Loss
Vertigo Conductive: WIDENING
The illusion of movement: usually rotatory Wax or foreign body
Of patient or surroundings Infection: otitis media, OME
Worse on movement Drum perforation
Extra: ossicle discontinuity otosclerosis, trauma
Not Vertigo Neoplasia: carcinoma
Faintness INjury: e.g. barotrauma
Light-headedness Granulomatous: Wegeners, Sarcoid
Lost awareness
Dizziness Sensorineural: DIVINITY

c Impaired consciousness = blackout
w/o impaired consciousness Developmental
Vertigo: vestibular Genetic: Alports, Waardenburgs
Imbalance: vestibular, cerebellar, extrapyramidal Congenital: TORCH
Perinatal: anoxia
Causes of Vertigo: IMBALANCE Degenerative

Presbyacusis
Infection / Injury
Labyrinthitis: post-viral severe vertigo, n/v Infection
Ramsay Hunt VZV, measles, mumps, influenza
Trauma: to petrous temporal bone Meningitis
Menieres
Recurrent vertigo (~20min) n/v Vascular
Fluctuating SNHL Ischaemia: Internal Auditory Artery (AICA) sudden
Tinnitus hearing loss and vertigo
Aural fullness Stroke
Benign Positional Vertigo
Sudden vertigo provoked by head rotation Inflammation
Aminoglycosides / frusemide Vasculitis
Lymph, Peri-, fistula Sarcoidosis
Path: Connection between inner and middle ears
Causes: Congenital, trauma Neoplasia
PC: vertigo, SNHL CPA tumours: acoustic neuroma (commonest cause
o/e: Tullios phen nystagmus evoked by loud of unilateral SNHL)
sound
Arterial Injury
Migraine Noise
TIA / stroke Head trauma
Nerve
Acoustic neuroma / vestibular schwannoma Toxins
Central lesions Gentamicin
Demyelination, tumour, infarct (e.g. LMS) Frusemide
Epilepsy Aspirin
Complex partial
lYmph
Endolymphatic Hydrops = Menieres
Perilymphatic fistula: ruptured round window

Abnormal Involuntary Movements Dyskinesias
Tremor Dystonia
Regular, rhythmic oscillation Prolonged muscle contracture unusual joint posture
NB. Asterixis = rhythmic myoclonus or repetitive movements
Types and Causes: RAPID Idiopathic generalised dystonia

Often autosomal dominant
Resting Childhood onset: starts in one leg and spreads on that
Features side of the body over 5-10yrs
4-6Hz, pill-rolling
Abolished on voluntary movement Idiopathic focal dystonia
c distraction (e.g. counting backwards) Commonest form of dystonia
Causes: Parkinsonism Confined to one part of the body
Rx: Da agonists, antimuscarinic (e.g. procyclidine) Worsened by stress
Types:
Action / Postural Spasmodic torticollis
Features Blepharospasm
6-12Hz Oromandibular
Absent at rest Writers / Muscicians cramp
Worse c outstretched hands or movement
Equally bad at all stages of movement Acute Dystonia
Causes: BEATS Torticollis, trismus and/or occulogyric crisis
Benign essential tremor Typically a drug reaction:
Endocrine: thyroxicosis, glucose, phaeo Neuroleptics
Alcohol withdrawal (or caffeine, opioids) Metoclopramide
Toxins: -agonists, theophylline, valproate, PHE L-DOPA
Sympathetic: physiological tremor may be Rx: procyclidine (antimuscarinic)
enhanced: e.g. in anxiety
Chorea
Intention Non-rhythmic, purposeless, jerky, flitting movements
Features E.g. facial grimacing, flexing / extending the fingers
>6Hz, irregular, large amplitude Causes
Worse at end of movement Huntingtons
E.g. past-pointing Sydenhams
Causes: cerebellar damage Wilsons
L-DOPA
Dystonic
Features: variable
Athetosis
Causes: mostly idiopathic, as for dystonia
Slow, sinuous, writhing movements
Causes
Benign Essential Tremor Cerebral palsy
Autosomal dominant Kernitcterus
Occur c action and worse
c anxiety, emotion, caffeine
Arms, neck, voice Hemiballismus
Doesnt occur during sleep Large amplitude, flinging hemichorea
Better
c EtOH Contralateral to a vascular lesion in the subthalamic
nucleus: often elderly diabetics
Recovers spontaneously over months
Myoclonus
Sudden, involuntary jerks Tardive Syndromes
Delayed onset following chronic exposure to Da
Causes agonists (e.g. antipsychotics, antiemetics, L-DOPA)
Metabolic = Asterixis (L, R, CO2)
Neurodegenerative diseases (LSDs) Classification
CJD Dyskinesia: orobuccolingual, truncal or choreifirm
Myoclonic epilepsies (e.g. infantile spasms) movements
Dystonia: sustained, stereotyped muscle spasms of
Benign Essential Myoclonus twitching or turning
Auto dom Akathisia: unpleasant sense of inner restlessness
Childhood onset frequent generalised myoclonus w/o repetitive movements (e.g. pacing)
progression.
May respond to valproate Rx
Change (e.g. to atypical) or slowly withdraw drug
Dyskinesia: Da antagonist (tetrabenazine)
Akathisia: -B

Dementia Delirium / ACS
Chronically impaired cognition that affects multiple Globally impaired cognition and impaired consciousness
domains: memory, attention, language
No impairment of consciousness Features
Acquired and progressive (cf. LD) Disorientation to person, time and place
Reversal of sleep-wake cycle (hyperactive at night)
Alzheimers Disease Labile mood
Epi: 50% Illusions, delusions and hallucinations
Path: neurofibrillary tangles and amyloid plaques Cognitive impairment: mem, language, concentration
PC: progressive, global cognitive decline
RFs: ApoE4 allele, presenillin 1/2 mutations, Downs Causes: DELIRIUMS
Ix: MRI medial temporal lobe atrophy
Rx: cholinesterase inhibitors (donepezil, rivastigmine) if Drugs: opioids, sedatives, L-DOPA
MMSE is 10-20 Eyes, ears and other sensory deficits
Low O2 states: MI, stroke, PE
Vascular Dementia Infection
Epi: 20% Retention: stool or urine
Path: multiple infarcts Ictal
PC: sudden onset, stepwise deterioration, patchy Under- hydration / -nutrition
deficits, vascular RFs Metabolic: DM, post-op, sodium, uraemia
Ix: MRI extensive infarcts or small vessel disease Subdural haemorrhage or other intracranial pathology
Rx: manage predisposing factors
Ix
Lewy Body Dementia Bloods: FBC, U+E, LFTs, glucose, ABG
Epi: 20% Urine dip
Path: Lewy Bodies in occipito-parital cortex Septic screen
PC: Fluctuating cognitive dysfunction, visual ECG, LP
hallucinations, parkinsonism
Rx: cholinesterase inhibitors Mx
ID and Rx underlying cause
Frontotemporal Dementia (Picks) Surround c familiar people
Epi: <5% Nurse in moderately lit, quiet room
Path: Pick Bodies Find glasses, hearing aids
PC: disinhibition, personality change, early memory Avoid sedatives if possible, but if disruptive:
preservation, progressive aphasia Haldol 0.5-2mg PO/IM
Ix: MRI frontal or temporal atrophy Chlorpromazine 50-100mg PO/IM (avoid in elderly)
Ameliorable Causes
Infection
Viral: HIV, HSV, PML
Helminth: cysticercosis, toxo
Vascular
Chronic subdural haematoma
Inflammation
SLE
Sarcoid
Neoplasia
Nutritional
Thiamine deficiency
B12 and folate deficiency
Pellagra (B3 / niacin deficiency)
Hypothyroid
Hypoadrenalism
Hypercalcaemia
Hydrocephalus (normal pressure)

Headache: Differential and Investigation
Acute: VICIOUS Chronic: MCD TINGS
Vascular Migraine
Haemorrhage: SAH, intracranial, intracerebral
Infarction: esp. posterior circulation Cluster headaches
Venous: Sinus / cortical thrombosis
Drugs
Infection/Inflammation Analgesics
Meningitis Caffeine
Encephalitis Vasodilators: Ca2+ antagonists, nitrates
Abscess
Tension headaches
Compression
Obstructive hydrocephalus: tumour ICP /
Pituitary enlargement: apoplexy : tumour, aneurysm, AVM, benign intracranial HTN
: spontaneous intracranial hypotension
ICP
Spontaneous intracranial hypotension Neuralgia (trigeminal)
Acute dural CSF leak
Worse on standing initially. Giant cell arteritis
Ophthalmic
Systemic
Acute glaucoma
HTN
Organ failure: e.g. uraemia
Unknown
Situational: cough, exertion, coitus
Systemic
HTN: Phaeo, PET
Infection: sinusitis, tonsillitis, atypical pneumonia
Toxins: CO
Investigations:
Bloods
Urine
Micro
Blood cultures
Serology: enterovirus (common cause of viral meningitis), HSV, HIV, syphilis, crypto
CSF
Radiology
Non-contrast CT
SAH: blood in sulci, cisterns (white). 90% sensitivity in first 24h
MRI
MRA: aneurysm
MRV: sinus thrombosis
Special: CSF
Opening pressure (norm = 5-20cm H2O):
: SAH, meningitis
: spontaneous intracranial hypotension
Xanthochromia: yellow appearance of CSF due to bilirubin. Detect by spectrophotometry.
Findings Bacterial TB Viral

Appearance Turbid Fibrin web Clear
Cells PMN Lympho / mononuc Lympho / mononuc
Count 100-1000 10-1000 50-1000
Glucose (< plasma) (< plasma) > plasma
Protein (g/L) (>1.5) (1-5) mild (<1)

Headaches: Key Features
SAH Hemicrania
Sudden onset, worst ever, occipital headache. Paroxysmal hemicranias: cluster-like headache lasting
Meningism, focal signs, consciousness 5-45min, 5-30x/day
SUNCT: short-lasting unilateral neuralgia with
Venous Sinus Thrombosis conjunctival injection and tearing, attacks last 15-60s,
Sagittal: headache, vomiting, seizures, vision, recur 5-30x/hr
papilloedema Hemicrania continua: continuous cluster-like headache
Transverse: headache mastoid pain, focal CNS Rx: all respond well to indomethacin
signs, seizures, papilloedema
Trigeminal neuralgia
Cortical Vein Thrombosis Paroxysms of unilateral intense stabbing pain in
Thunderclap headache trigeminal distribution (usually V2/3)
Stroke-like focal symptoms over days Triggers: washing area, shaving, eating, talking
Focal seizures are common Male > 50yrs
2O in 14%: compression of CNV, MS, Zoster, Chiari
Meningitis malformation
Fever, photophobia, neck stiffness, kernigs +ve Ix: exclude 2O cause by MRI.
Purpuric rash Rx Med: CBZ, lamotrigine, gabapentin
consciousness Rx Surg: microvascular decompression
Encephalitis Analgesia Overuse

Fever, odd behaviour, fits, focal neuro, consciousness Episodic headache becomes daily chronic headache
Use OTC analgesia on 6 days/month max
Acute Glaucoma
Constant unilat eye pain, radiating to forehead ICP
acuity, haloes, n/v : worse in AM, stooping, visual probs (papilloedema),
Red eye, cloudy cornea. obese women
Dilated, non-responsive pupil : worse sitting or standing
Tension Headache TMJ Dysfunction

Bilateral / vertex-bitemporal, non-pulsatile, band-like Preauricular pain on chewing
Assoc.
c crepitus
Migraine Earache, headache
Prodrome aura headache
Unilat, throbbing Giant Cell Arteritis (>60yrs, ESR>60, pred 60mg)
n/v, phono/photophobia Unilateral temple/scalp pain and tenderness.
Thickened, pulseless temporal artery
Cluster Jaw claudication, amaurosis fugax, sudden blindness
Rapid onset very severe pain around/behind one eye. Assoc. c PMR in 50%
Red, watery eye, nasal congestion Ix: ESR, plats, ALP, Hb, temporal artery biopsy
Miosis, ptosis Rx
Attacks last 15min3hrs, 1-2x/day, mostly nocturnal High dose pred (60mg/d PO) for 5-7d
Clusters last 4-12wks, remission lasts 3mo-3yrs. Can Guided by symptoms and ESR.
be chronic vs. episodic. Give PPI+bisphosphonate.
Rx: 100% O2 via non-rebreathe mask, Sumitriptan Prog: 2yr course then complete remission
Prevention: verapamil, topiramate, Li

Migraine
Epidemiology Diagnostic Criteria
8% prev Typical aura + headache, or
F:M = 2:1 5 headaches lasting 4-72h with either n/v or
photo/phonophobia + 2 of:
Risk Factors Unilat
Obesity Pulsating
PFO Interferes with normal life
Worsened by routine activity
Pathophysiology
Vascular: cerebrovascular constriction aura,
dilatation headache. Differential
Brain: spreading cortical depression Cluster / tension headache
Inflammation: activation of CN V nerve terminals in Cervical spondylosis
meninges and cerebral vessels. HTN
Intracranial pathology
Triggers Epilepsy
CHOCOLATE
CHeese
OCP Treatment
Caffeine
alcohOL Acute episode
Anxiety 1st: Paracetamol + metoclopramide / domperidone
Travel 2nd: NSAID (e.g. ketoprofen) + M/D
Exercise 3rd: Rizatriptan
CI: IHD, uncontrolled HTN, SSRIs
Symptoms 4th: ergotamine
Headache Prophylaxis
Aura lasting 15-30min then unilat, throbbing Avoid triggers
headache 1st: Propanolol, topiramate
Phono/photophobia 2nd: Valproate, pizotifen ( wt.), gabapentin
n/v
Allodynia
Often premenstrual
Prodrome (50%): precede migraine by hrs - days

Yawning
Food cravings
Changes in sleep, appetite or mood
Aura (20%): precedes migraine by mins and may persist

Visual: distortion, lines, dots, zig-zags, scotoma,
hemianopia
Sensory: paraesthesia (fingers face)
Motor: dysarthria, ataxia, ophthalmoplegia,
hemiparesis (hemiplegic migraine)
Speech: dysphasia, paraphasia
Classification
Migraine
c aura (classical migraine)
Migraine w/o aura (common migraine)

Subarachnoid Haemorrhage
Epidemiology Investigations
9/100,000
35-65yrs CT
Detects >90% of SAH w/i first 48hrs
Causes
Rupture of saccular aneurysms (80%) LP
AVMs (15%) If CT-ve and no CIs >12h after start of headache
Xanthochromia due to breakdown of bilirubin
Risk Factors
Smoking Mx
HTN Frequent neuro obs: pupils, GCS, BP
EtOH Maintain CPP: keep SBP >160
Bleeding diathesis Nimodipine for 3wks cerebral vasospasm
Mycotic aneurysms (SBE) Endovascular coiling (preferable to surgical clipping)
FH (close relatives have 3-5x risk)
Berry Aneurysms Complications
Sites Rebleeding: 20%

Junction of post. communicating
c IC Commonest cause of mortality
Junction of ant. communicating
c ACA
Cerebral Ischaemia
Bifurcation of MCA
Due to vasospasm
Associations Commonest cause of morbidity
Adult polycystic kidneys
Hydrocephalus
CoA
Due to blockage of arachnoid granulations
Ehlers Danlos
May require ventricular or lumbar drain
Symptoms Hyponatraemia
Sudden, severe occipital headache Common
Collapse Dont Mx
c fluid restriction
Meningism: neck stiffness, n/v, photophobia
Seizures
Drowsiness coma
Mx of Unruptured Aneurysms
Young pts. c aneurysms >7mm in diameter may
Signs benefit from surgery.
Kernigs
Retinal or subhyaloid haemorrhage
Focal neuro
@ presentation suggests aneurysm location
Later deficits suggests complications
Sentinel Headache
~6% of pts. experience sentinel headache from small
warning bleed.
Differential
In 1O care, 25% of those c thunderclap headache
have SAH
50-60% no cause found
Rest: meningitis, intracerebral bleeds, cortical vein
thrombosis

Stroke: Causes and Investigation
Definition
Rapid onset, focal neurological deficit due to a vascular lesion lasting >24h
Pathogenesis Ix
Infarction due ischaemia (80%) or intracerebral ID risk factors for further strokes
haemorrhage (20%).
HTN
Ischaemia (80%) Retinopathy
Atheroma Nephropathy
Large (e.g. MCA) Big heart on CXR
Small vessel perforators (lacunar) (Dont treat acutely)
Embolism
Cardiac (30% of strokes):AF, endocarditis, MI Cardiac emboli
Atherothromboembolism: e.g. from carotids ECG 24hr tape: AF
Echo: mural thrombus, hypokinesis, valve lesions, ASD,
Haemorrhage (20%) VSD (paradoxical emboli)
BP
Trauma Carotid artery stenosis
Aneurysm rupture Doppler US angio
Anticoagulation Endarterectomy beneficial if 70% symptomatic
Thrombolysis stenosis
Rarer Causes Bleeding / thrombotic tendency

Watershed stroke: sudden in BP (e.g. in sepsis) Thrombophilia screen
Carotid artery dissection Thrombocytopenia
Vasculitis: PAN, HIV
O
Cerebral vasospasm 2 to SAH Hyperviscosity
Venous sinus thrombosis Polycythaemia
Anti-phospholipid syndrome, thrombophilia SCD
Myeloma
Risk Factors Metabolic

HYPERTENSION glucose
Smoking, DM, lipids, FH lipids
Cardiac: AF, valve disease Hyperhomocystinaemia
Peripheral vascular disease
Vasculitis
Previous history
ESR
Ethnicity: in Blacks and Asians
ANA
PCV/Hct
OCP
Cardiac Causes of Stroke

AF: 4.5% /yr
External cardioversion: 1-3%
Prosthetic valves
Acute MI: esp. large anterior
Paradoxical systemic emboli
Cardiac surgery
Valve vegetations

Stroke: Presentation
Oxford / Bamford Classification Brainstem Infarcts
Based on clinical localisation of infarct Complex signs depending on relationship of infarct to
S=syndrome: prior to imaging CN nuclei, long tracts and brainstem connections
I=infarct: after imaging when atheroembolic infarct
confirmed Features
Feature Structure
Total Anterior Circulation Stroke (TACS) Hemi- / quadr-paresis Corticospinal tracts
Highest mortality (60% @ 1yr) + poor independence Conjugate gaze palsy Oculomotor system
Large infarct in carotid / MCA, ACA territory
All 3 of: Horners syndrome Sympathetic fibres
1. Hemiparesis (contralateral) and/or sensory deficit Facial weakness (LMN) CN7 nucleus
(2 of face, arm and leg)
2. Homonymous hemianopia (contralateral) Nystagmus, vertigo CN8 nucleus
3. Higher cortical dysfunction Dysphagia, dysarthria CN9 and CN10 nuclei
Dominant (L usually): dysphasia
Dysarthria, ataxia Cerebellar connections
Non-dominant: hemispatial neglect
GCS Reticular activating syndrome
Partial Anterior Circulation Stroke (PACS)

Carotid / MCA and ACA territory Lateral Medullary Syndrome / Wallenbergs Syndrome
2/3 of TACS criteria, usually: PICA or vertebral artery
1. Hemiparesis (contralateral) and/or sensory deficit
Features: DANVAH
(2 of face, arm and leg)
Dysphagia
2. Higher cortical dysfunction
Ataxia (ipsilateral)
Dominant: dysphasia Nystagmus (ipsilateral)
Non-dom: neglect, constructional apraxia Vertigo
Deficit is less dense and/or incomplete Anaesthesia
Ipsilat facial numbness + absent corneal
reflex
Posterior Circulation Stroke (POCS) Contralateral pain loss
Infarct in vertebrobasilar territory Horners syndrome (ipsilateral)
Any of
1. Cerebellar syndrome
2. Brainstem syndrome Millard-Gubler Syndrome
3. Contralateral homonymous hemianopia Pontine infarct
th th
6 and 7 CN nuclei + corticospinal tracts
Diplopia
Lacunar Stroke (LACS) LMN facial palsy + loss of corneal reflex
Small infarcts around basal ganglia, internal capsule, Contralateral hemiplegia
thalamus and pons.
Absence of
Higher cortical dysfunction
Locked-in Syndrome
Homonymous hemianopia
Pt. is aware and cognitively intact but completely
Drowsiness
paralysed except for the eye muscles.
Brainstem signs
Causes
5 syndromes
Ventral pons infarction: basilar artery
Pure motor: post. limb of internal capsule
Central potine myelinolysis: rapid correction of
Commonest
hyponatraemia
Pure sensory: post. thalamus (VPL)
Mixed sensorimotor: internal capsule
Dysarthria / clumsy hand
Ataxic hemiparesis: ant. limb of internal capsule Stroke Differential
Weakness + dysmetria Head injury haemorrhage
glucose
SOL
Other Signs Hemiplegic migraine
Ischaemic pointers Todds palsy
Carotid bruit Infections: encephalitis, abscesses, Toxo, HIV, HTLV
AF Drugs: e.g. opiate overdose
Past TIA
IHD
Haemorrhagic pointers
Meningism
Severe headache
Coma
Stroke: Management
Acute Management Primary Prevention
Control RFs: HTN, lipids, DM, smoking, cardiac
Resuscitate disease
Ensure patent airway: consider NGT Consider life-long anticoagulation in AF (use CHADS2)
NBM until swallowing assessed by SALT Carotid endarterectomy if symptomatic 70% stenosis
Dont overhydrate: risk of cerebral oedema Exercise
Monitor
Glucose: 4-11mM: sliding scale if DM Secondary Prevention
BP: <185/110 (for thrombolysis) Risk factor control as above
Rx of HTN can cerebral perfusion Start a statin after 48h
Neuro obs Aspirin / clopi 300mg for 2wks after stroke then either
Clopidogrel 75mg OD (preferred option)
Imaging Aspirin 75mg OD + dipyridamole MR 200mg BD
Urgent CT/MRI Warfarin instead of aspirin/clopidogrel if
Diffusion-weighted MRI is most sensitive for acute infarct Cardioembolic stroke or chronic AF
CT will exclude primary haemorrhage Start from 2wks post-stroke (INR 2-3)
Dont use aspirin and warfarin together.
Medical Carotid endarterectomy if good recovery + ipsilat
Consider thrombolysis if 18-80yrs and <4.5hrs since stenosis 70%
onset of symptoms
Alteplase (rh-tPA)
death and dependency (OR 0.64) Rehabilitation: MENDS
CT 24h post-thrombolysis to look for haemorrhage MDT: physio, SALT, dietician, OT, specialist nurses,
Aspirin 300mg PO/PR once haemorrhagic stroke neurologist, family
excluded PPI Eating
Clopidogrel if aspirin sensitive Screen swallowing: refer to specialist
NG/PEG if unable to take oral nutrition
Surgery Screen for malnutrition (MUST tool)
Neurosurgical opinion if intracranial haemorrhage Supplements if necessary
May coil bleeding aneurysms Neurorehab: physio and speech therapy
Decompressive hemicraniectomy for some forms of MCA Botulinum can help spasticity
infarction. DVT Prophylaxis
Sores: must be avoided @ all costs
Stroke Unit
Specialist nursing and physio
Early mobilisation
Occupational Therapy
DVT prophylaxis
Impairment: e.g. paralysed arm
Secondary Prevention Disability: e.g. inability to write
Handicap: e.g. cant work as accountant
Rehabilitation OT aims to minimise disability and abolish handicap
Prognosis @ 1yr
10% recurrence
PACS
20% mortality
1/3 of survivors independent
2/3 of survivors dependent
TACS is much worse
60% mortality
5% independence

Transient Ischaemic Attack
Definition Mx: ACAS
Sudden onset focal neurology lasting <24h due to Time to intervention is crucial.
temporary occlusion of part of the cerebral circulation. Intervention w/i 72hrs 2% strokes @ 90d
~15% of 1st strokes are preceded by TIAs. Intervention w/i 3wks 10% strokes @ 90d
Avoid driving for 1mo
Signs
Symptoms usually brief
Global events (e.g. syncope, dizziness) are not typical 1. Antiplatelet Therapy / Anticoagulate
Signs mimic those of CVA in the same arterial territory Aspirin/clopi 300mg/d for 2wks then 75mg/d
Add dipyridamole MR to aspirin
Warfarin if cardiac emboli: AF, MI, MS
Signs of Causes
After 2wks
Carotid bruits
BP 2. Cardiac Risk Factor Control
Heart murmur BP, lipids, DM, smoking
AF Exercise
Diet: salt
Causes
Atherothromboembolism from carotids is main cause 3. Assess risk of subsequent stroke
Cardioembolism: post-MI, AF, valve disease ABCD2 score
Hyperviscosity: polycythaemia, SCD, myeloma
4. Specialist referral to TIA clinic
Differential ABCD2 4: w/i 24hrs
Vascular: CVA, migraine, GCA ABCD2 <4: w/i 1wk
Epilepsy
Hyperventilation Carotid Endarterectomy
Beneficial if 70% symptomatic stenosis
Hypoglycaemia
50-70% stenosis may benefit if operative risk is <3%
Surgery should be performed w/i 2wks.
Ix
Endovascular stenting is an alternative, but safety and
Aim to find cause and define vascular risk
long-term benefits (in-stent restenosis is common) are
Bloods: FBC, U&E, ESR glucose, lipids still under Ix.
CXR Major complications are stroke and death.
ECG
Echo
Carotid doppler angiography
Consider brain imaging
Prognosis
Diffusion weighted MRI is best Combined risk of stroke and MI is ~9%/yr
3x in mortality cf TIA-free populations
ABCD2 Score
Predicts stroke risk following TIA
Score 6 = 8% risk w/i 2d, 35% risk w/i 1wk
Score 4 = pt. assessment by specialist w/i 24hrs
All pts with suspected TIA should be seen by specialist
w/i 7d.
1. Age 60
2. BP 140/90
3. Clinical features
a. Unilateral weakness (2 points)
b. Speech disturbance w/o weakness
4. Duration
a. 1h (2 points)
b. 10-59min
5. DM
NB. 7 points max.

Subdural Haemorrhage Extradural Haemorrhage
Bleeding from bridging veins between cortex and Often due to # temporal or parietal bone laceration of
sinuses middle meningeal artery and vein.
Haematoma between dura and arachnoid Blood between bone and dura
Often due to minor trauma that occurred a long time Suspect if after head injury GCS falls, is slow to
previously especially deceleration injuries improve or there is a lucid interval.
Risk Factors Presentation

Elderly: brain atrophy
Falls: epileptics, alcoholics Lucid Interval
Anticoagulation Deterioration of GCS after head injury that caused no
LOC, or following initial improvement in GCS.
Lucid interval may be hrs or days
Symptoms
Headache ICP
Fluctuating GCS, sleepiness Headache
Gradual physical or mental slowing Vomiting
Unsteadiness Confusion coma
Fits
rd
Ipsilateral blown pupil (3 nerve palsy)
Signs hemiparesis c upgoing plantars and reflexes
ICP (can tentorial herniation)
Localising signs occur late Brainstem Compression
Deep irregular breathing (brainstem compression)
Cushing response (BP, HR) is late
Imaging: CT / MRI Death by cardiorespiratory arrest
Crescentic haematoma over one hemisphere
Clot goes from white grey
c time
Mid-line shift
Imaging: CT
Lens-shaped haematoma
Skull # ( risk of extradural haemorrhage)
Mx
1st line: irrigation/evacuation via burr-hole craniostomy
2nd line: craniotomy
Mx
Neuroprotective ventilation (O2>100, CO2 35-40)
Address causes of trauma
Consider mannitol (1g/kg IV via central line)
Craniectomy for clot evacuation and vessel ligation
Differential
Stroke
Dementia
SOL

Intracranial Venous Thrombosis
Dural Venous sinus Thrombosis Common Causes
Symptoms come one gradually over days-wks Pregnancy / puerperium
Sinus thrombosis may extend to cortical veins OCP
Head injury
Sagittal Sinus Dehydration
45% of IVT Intracranial / extracranial malignancy
Often co-exists if other sinuses are thrombosed Thrombophilia
Headache, vomiting, seizures, vision, papilloedema
Transverse Sinus Ix
35% of IVT
Exclude SAH and meningitis
Headache mastoid pain, focal neuro, seizures,
CT/MRI venography: absence of a sinus
papilloedema
LP: pressure, may show RBCs and xanthochromia
Sigmoid Sinus
Cerebellar signs, lower CN palsies
Mx
Inferior Petrosal Sinus LMWH warfarin (INR 2-3)
th th
5 and 6 CN palsies (Gradenigos syn.) Fibrinolytics (e.g. streptokinase) can be used via
selective catheterisation.
Cavernous sinus Thrombophilia screen
Spread from facial pustules or folliculitis
Headache, chemosis, eyelid oedema, proptosis, painful
ophthalmoplegia, fever
Cortical Vein Thrombosis

Often venous infarcts
c stroke-like focal symptoms
that evolve over days
Thunderclap headache
Focal-seizures
Differential
SAH
Meningitis
Encephalitis
Intracranial abscess
Arterial stroke

Meningitis
Features Abx Therapy
Community: benpen 1.2g IV/IM
Meningitic <50: ceftriaxone 2g IVI/IM BD
Headache >50: ceftriaxone + ampicillin 2g IVI /4h
Neck stiffness If viral suspected: aciclovir
c hip @ 90O
Kernigs: Straightening leg
Brudzinskis: lifting head lifting of legs Organisms
Photophobia Viruses: enteroviruses (Coxsackie, echovirus), HSV2
n/v Meningococcus
Pneumococcus
Neurological
Listeria
GCS coma
Haemophilus
Seizures (20%)
TB
Focal neuro (20%): e.g. CN palsies
Cryptococcus
Septic
Fever Ix
BP, HR Bloods: FBC, U+Es, clotting, glucose, ABG
CRT Blood cultures
Purpuric rash LP: MCS, glucose, virology/PCR, lactate
DIC
Acute Management
ABC
O2 15L SpO2 94-98%
IVI fluid resus
c crystalloid
Mainly Septicaemic Mainly Meningitic

Dont attempt LP If no shock or CIs do LP
Ceftriaxone 2g IVI Dexamethasone 0.15mg/kg IV QDS
Consider ITU if shocked Ceftriaxone 2g IVI post-LP
Continuing Management
Ceftriaxone 2g BD IVI
Meningococcus: 7d IV then review
Pneumococcus: 14d IV then review
Maintenance fluids
UO 30ml/h
SBP >80mmHg
If response is poor, consider intubation inotropic support
Rifampicin prophylaxis for household contacts.
CIs to LP: Try LP Unless ContraINdicated CSF Findings

Thrombocytopenia
Lateness (delay in antibiotic admin)
Pressure (signs of raised ICP)
Cells PMN Lympho / Lympho /
Unstable (Cardio + resp systems) mononuc mononuc
Coagulation disorder Count 100-1000 10-1000 50-1000
Infection at LP site Glucose (< (< > plasma
Neurology (focal neurological signs) plasma) plasma)
Protein (g/L) (>1.5) (1-5) mild (<1)

Encephalitis Cerebral Abscess
Presentation Pre-disposing Factors
Infectious prodrome: fever, rash, LNs, cold sores, Infection: ear, sinus, dental or periodontal
conjunctivitis, meningeal signs. Skull #
Bizarre behaviour or personality change Congenital heart disease
Confusion Endocarditis
GCS coma Bronchiectasis
Fever Immunosuppression
Headache
Focal neuro Organisms
Seizures Frontal sinus/teeth: strep. Milleri, oropharyngeal
Hx of travel or animal bite anaerobes
Ear: Bacteroides, other anaerobes
Causes
Signs
Usually viral Seizures
HSV1/2 Fever
CMV, EBV, VZV Localizing signs
Arboviruses Signs of ICP
HIV Signs of infection elsewhere
Non-viral Ix
Any bacterial meningitis CT/MRI: ring-enhancing lesion
TB WCC, ESR
Malaria
Lyme disease
Rx
Neurosurgical referral
Ix Abx: e.g. ceftriaxone
Bloods: cultures, viral PCR, malaria film Treat ICP
Contrast CT: focal bilat temporal involvement
suggests HSV
LP: CSF protein, lymphocytes, PCR
EEG: shows diffuse abnormalities, may confirm Dx
Mx
Aciclovir STAT: 10mg/kg/8h IVI over 1h for 14/7
Supportive measures in HDU/ITU
Phenytoin for seizures
Prognosis
70% mortality if untreated
w/o fever, consider encephalopathy

glucose
Hepatic
DKA
Drugs
SLE
Uraemia
Hypoxic brain injury
Beri-Beri

Epilepsy: Features
Definition Presenting Features
Recurrent tendency to spontaneous, intermittent,
abnormal electrical activity in part of the brain, manifest Simple Partial
as seizures. Focal motor, sensory, autonomic or psychic symptoms
Causes Complex Partial: 5As

2/3 are idiopathic (often familial) Aura
Congenital Autonomic: change in skin colour, temperature, palps
NF Awareness lost: motor arrest, motionless stare
Tuberous Sclerosis Automatisms: lip-smacking, fumbling, chewing,
TORCH swallowing
Perinatal anoxia Amnesia
Acquired
Vascular: CVA NB. Usually arise from temporal lobe
Cortical scarring: trauma, infection
SOL Absences (Petit mal)
Other: SLE, PAN, MS, sarcoidosis ABrupt onset and offset
Non-epileptic / provoked seizures Short: <10s
Withdrawal: EtOH, opiates, benzos Eyes: glazed, blank-stare
Metabolic: glucose, Na, Ca, urea, NH3 Normal: intelligence, examination, brain-scan
ICP: trauma, haemorrhage, cortical venous Clonus or automatisms may occur
thrombosis EEG: 3Hz spike and wave
Infection: meningitis, encephalitis, cycticerosis, Stimulated by hyperventilation and photics
HIV
Eclampsia Tonic-Clonic (Grand mal)
Pseudoseizures LOC
Tonic: limbs stiffen
NB. 3-10% of provoked seizures tend to recur, cf 30-50% of Clonic: rhythmic jerking of limbs
unprovoked seizures cyanosis, incontinence, tongue biting (lateral)
Post-ictal confusion and drowsiness
Seizure Terms
Prodrome Myoclonic Seizure
pt. or others may notice change in mood or Sudden jerk of limb, face or trunk.
behaviour lasting hrs days.
Not part of seizure. Atonic (akinetic seizures)
Aura Sudden loss of muscle tone fall
A simple partial seizure (usually temporal) which No LOC
may precede other manifestations.
Experienced as a strange feeling: West Syndrome / Infantile Spasms
Epigastric rising Clusters of head nodding and arm jerks
Deja/jamias vu, EEG shows hypsarrhythmia
Automatisms,
Smells, lights, sounds
Partial (focal) Localising Features
Features referable to part of one hemisphere
Primary Generalised Temporal
No warning / aura
Automatisms: lip smacking, chewing, fumbling
Discharge throughout cortex w/o localising
Deja/jamias vu
features
Delusional behaviour
Simple: awareness unimpaired
Abdominal: rising, n/v
Complex: awareness impaired
Emotional disturbance: terror, panic, anger, elation
Secondary Generalised
Tastes, smells
Focal seizure generalised
E.g. aura tonic-clonic
Frontal
Motor features: arrest, Jacksonian march, Todds palsy
Diagnostic Pointers Parietal
Aura Sensory disturbance: tingling, numbness
Specific trigger: e.g. flashing lights
Lateral tongue biting (> incontinence) Occipital
Typical movements: e.g. tonic-clonic Visual phenomena: spots, lines, flashes
Cyanosis
Post-ictal phase

Epilepsy: Investigation and Management
General Principles Side Effects of Common AEDs
After any seizure advise against driving, swimming,
et.c. until a Dx is established Enzyme Effects
Dont diagnose epilepsy from a single seizure Inducers: CBZ, PHE and barbiturates
Diagnosis should be made by a specialist Inhibitors: Valproate
After Dx, cannot drive until seizure-free for >1yr
10yrs for HGV (no meds) Lamotrigine
Skin rash SJS: occurs w/i 1st 8wks
Rash may be assoc. c hypersensitivity fever, LFTs,
Investigations DIC.
Basic bloods: FBC, U+Es, glucose Diplopia, blurred vision
Se Prl 10min after fit (relative to baseline) Levels affected by enzyme inhibitors/inducers
Se AED levels
Urine toxicology Valproate
ECG Appetite wt.
st
Liver failure: monitor LFTs over 1 6mo
EEG Pancreatitis
Use to support Dx (cannot exclude or prove) Reversible hair loss
Helps classification and prognosis Oedema
Use
c hyperventilation and photic stimulation Ataxia
Teratogenicity, Tremor, Thrombocytopaenia
Neuroimaging: typically MRI Encephalopathy: due to ammonia
Not routine for idiopathic generalised epilepsy
Indications Carbamazepine
Developed epilepsy as an adult Leukopenia
Any evidence of focal onset Skin reactions
st
Seizures continue despite 1 -line Rx Diplopia, blurred vision
SIADH hyponatraemia
Drug Therapy Phenytoin

Gingival hypertrophy
Seizure Type 1st line 2nd line Hirsutism
Tonic-Clonic Valproate Lamotrigine Cerebellar syn.
Absences Valproate Lamotrigine Ataxia
Ethosuximide Nystagmus
Tonic, atonic or Valproate Levetiracetam Dysarthria
myoclonic Peripheral sensory neuropathy
Focal 2O gen Lamotrigine CBZ Diplopia
Tremor
In Women / Pregnancy
Avoid valproate: take lamotrigine (or CBZ)
5mg folic acid daily if child-bearing age
CBZ and PHE are enzyme inducers and the
effectiveness of the OCP
Other Options
Neurosurgical resection can be an option if a single
epileptogenic focus is identified
Vagal nerve stimulation can seizure frequency and
severity in ~33%

Status Epilepticus
Definition Drugs
Seizure lasting >30min, or
Repeated seizures w/o intervening consciousness Lorazepam
2-4mg IV bolus over 30s
Ix 2nd dose if no response w/i 2min
BM Alternatives:
Bloods: glucose, ABG, U+E, FBC, Ca2+ Diazepam 10mg IV/PR (20mg max)
ECG, EEG Midazolam 10mg buccal
Consider: AED levels, tox screen, LP, hCG, CT
Phenytoin
18mg/kg IVI @ 50mg/min
100mg/6-8h maintenance
Monitor ECG and BP
CI: bradycardia or heart block
Diazepam Infusion
100mg in 500ml 5% dex @ 40ml/hr (3mg/kg/24h)
Dexamethasone
10mg IV if vasculitis / cerebral oedema (tumour)
possible
Acute Management
ABC
Oral / nasal airway, intubate
Suction
100% O2
Capillary blood glucose
IV Access + Bloods
U+E, LFT, FBC, Glucose, Ca2+
AED levels
Tox screen
Reverse Potential Causes

Thiamine 250mg IV if EtOH
100ml 20% glucose unless glucose
known to be normal
Slow IV Bolus Phase

Lorazepam 2-4mg IV
2nd dose if no response w/i 2min
IV Infusion Phase
Phenytoin 18mg/kg IVI (then 100mg/6-8h)
Or, diazepam 100mg in 500ml 5% dex IVI
RSI Phase
Never spend >20min c someone in status w/o
getting an anaesthetist

Head Injury
Initial Mx Intubate
GCS 8
1O Survey PaO2 <9KPa on air / <13KPa on O2 or PCO2 >6KPa
A: ? intubation, immobilise C-spine Spontaneous hyperventilation: PCO2 <4KPa
B: 100% O2, RR Respiratory irregularity
C: IV access, BP, HR
D: GCS, pupils CT head guidelines: BANGS LOC
Treat seizures Break: open, depressed or base of skull
Lorazepam 2-4mg IV Amnesia >30min retrograde
Phenytoin18mg/kg IVI then 100mg/6-8h Neuro deficit or seizure
E: expose pt. and look for other obvious injuries GCS: <13 @ any time or <15 2h after injury
Sickness: vomited > once
2O Survey LOC or any amnesia and any of:
Look for: Dangerous mechanism: RTA, great height
Lacerations Age 65
Obvious facial/skull deformity Coagulopathy (inc. warfarin)
CSF leak from nose or ears
Battles sign, Racoon eyes
Blood behind TM
Risk of Intracranial Haematoma in Adults:
C-spine tenderness deformity Fully conscious, no skull # = <1:1000
Head-to-toe examination for other injuries Confused, no skull # = 1:100
Log role Fully conscious, skull # = 1:30
Confused, skull # = 1:4
Hx if possible
How and when? GCS
GCS and other vitals immediately after injury
Headache, fits, vomiting, amnesia, EtOH Eyes: 4
4 Spontaneous eye opening
Ix 3 Open to voice
Bloods: FBC, U+E, glucose, clotting, EtOH level, ABG 2 Open to pain
? CT head + c-spine 1 No opening
Verbal: 5
Rx 5 Orientated conversation
Neurosurgical opinion if signs of ICP, CT evidence of 4 Confused conversation
intracranial bleed significant skull # 3 Inappropriate speech
Admit if: 2 Incomprehensible sounds
Abnormalities on imaging 1 No speech
Difficult to assess: EtOH, post-ictal
Not returned to GCS 15 after imaging Motor: 6
CNS signs: vomiting, severe headache 6 Obeys commands
Neuro-obs half-hrly until GCS 15 5 Localises pain
GCS 4 Withdraws to pain
Pupils 3 Decorticate posturing to pain (flexor)
HR, BP 2 Decerebrate posturing to pain (extensor)
RR, SpO2 1 No movement
Temperature
Discharge Advice
Stay with someone for first 48hrs
Give advice card advising return on:
Confusion, drowsiness, unconsciousness
Visual problems
Weakness
Deafness
V. painful headache that wont go away
Vomiting
Fits

Space Occupying Lesions Idiopathic Intracranial Hypertension
Presentation Presentation
Typically obese females
ICP As if SOL
Headache: worse on waking, lying down, bending ICP
forward, coughing, straining. Headache
Vomiting Papilloedema
Papilloedema Visual
GCS Blurred vision
6th CN palsy
Seizures Enlarged blind spot
Exclude SOL in adult-onset seizures, especially c
localising aura or post-ictal weakness (Todds) Cause
Usually idiopathic
Evolving Focal Neurology May be 2O to venous sinus thrombosis or drugs
May be false-localising (esp. CN6 palsy)
Mx
Subtle Personality Change Wt. loss
Acetazolamide
Loop diuretics
Causes Prednisolone
Vascular: chronic subdural haematoma, AVM, Lumbar-peritoneal shunt may be necessary if drugs fail
aneurysm and visual loss deteriorates.
Infection: abscess, cyst (cysticercosis)
Neoplasm: primary or secondary Prognosis
Granuloma: TB, sarcoid Usually self-limiting
Permanent visual loss in 10%.
Tumours
30% metastatic: breast, lung, melanoma
Astrocytoma
Glioblastoma multiforme
Ependyoma
Meningiomas
Cerebellar haemangioblastoma
CNS lymphoma
Differential
Vasc: stroke, venous sinus thrombosis
Traumatic head injury
Infection: encephalitis
Inflam: vasculitis, MS
Metabolic disturbance
Idiopathic intracranial hypertension
Ix
CT or MRI (better for post. cranial fossa)
Consider biopsy

Raised ICP
Types of Cerebral Oedema
1. Vasogenic ( cap permeability): trauma, tumour, ischaemia, infection
2. Cytotoxic: e.g. from hypoxia
3. Interstitial: e.g. obstructive hydrocephalus, Na+
Causes Acute Management

Haemorrhage
ABC
Tumours
Infection: meningitis, encephalitis, abscess
Hydrocephalus
Status Treat seizures and correct hypotension
Cerebral oedema
Signs and Symptoms Elevate bed to 40O

Headache
n/v
Seizures Neuroprotective Ventilation
Drowsiness coma PaO2: >13KPa (100mmHg)
Cushings reflex: BP, HR, irregular breathing PCO2: 4.5kPa
6th CN palsy (may be false localising) Good sedation NM blockade
Cheyne-Stokes respiration
Pupils: constriction dilatation
Papilloedema, loss of venous pulsation @ disc
Mannitol or Hypertonic Saline
ICP short-term, but may rebound ICP later
Mannitol 1g/kg (20% @ 5ml/kg)
Herniation Syndromes
Tonsillar (Coning)
pressure in posterior fossa displacement of cerebellar tonsils through foramen magnum
compression of brainstem and cardioresp centres in medulla
CN6 palsy, upgoing plantars irregular breathing apnoea
Transtentorial / Uncal
Lateral supratentorial mass compression of ipsilateral inferomedial temporal lobe (uncus) against free margin of
tentorium cerebelli.
Ipsilateral CN3 palsy: mydriasis (dilation) then down-and-out
Ipsilateral corticospinal tract: contralateral hemiparesis
May compression of contralateral corticospinal tracts ipsilateral hemiparesis (Kernohans Notch: False Localising)
Subfalcine
Frontal mass
Displacement of cingulate gyrus (medial frontal lobe) under falx cerebri
Compression of ACA stroke
Contralateral motor/sensory loss in legs>arms
Abulia (pathological laziness)

Parkinsonism
Causes
Degenerative
1. Parkinsons disease
2. Parkinsons-plus syndromes (basal ganglia degeneration + other system)
a. Multiple Systems Atrophy / Shy-Drager

Autonomic dysfunction: post hypotension, bladder dysfunction
Cerebellar + pyramidal signs
Rigidity > Tremor
b. Progressive Supranuclear Palsy

Postural instability falls
Speech disturbance (+ dementia)
Palsy: vertical gaze
c. Corticobasilar Degeneration:
Aphasia, dysarthria, apraxia
Akinetic rigidity in one limb
Astereognosis (cortical sensory loss)
Alien limb phenomenon
d. Lewy Body Dementia:

Fluctuating cognition
Visual hallucinations
Infection
Syphilis
HIV
CJD
Vascular: Multiple infarcts in SN
Drugs: Antipsychotics, metoclopramide
Trauma: dementia pugilistica
Genetic: Wilsons disease
Symptoms
Tremor
Worse at rest
Exacerbated by distraction
4-6hz, pill-rolling
Rigidity
tone in all muscle groups: lead-pipe rigidity
Rigidity + tremor cog-wheel rigidity
Bradykinesia
Slow initiation of movement
c reduction of amplitude on repetition
Expressionless face
Monotonous voice
Micrografia
Gait
arm swing
Festinance
Freezing (esp. in doorways)

Parkinsons Disease
Epidemiology Ix
Mean onset 65yrs DaTSCAN
2% prevalence
Mx
Pathophysiology MDT: neurologist, PD nurse, physio, OT, social worker,
Destruction of dopaminergic neurones in pars compacta GP and carers
of substantia nigra. Assess disability
-amyloid plaques e.g. UPDRS: Unified Parkinsons Disease Rating Scale
Neurofibrillary tangles: hyperphosphorlated tau Physiotherapy: postural exercises
Depression screening
Features: TRAPPS PD Medical

Asymmetric onset: side of onset remains worst Young onset biologically fit
1. Da agonists: ropinirole, pramipexole
2. MOA-B inhibitors: rasagiline, selegiline
Tremor: by stress, by sleep
3. L-DOPA: co-careldopa or co-beneldopa
Rigidity: lead-pipe, cog-wheel
Akinesia: slow initiation, difficulty
c repetitive movement,
Biologically frail comorbidities
micrographia, monotonous voice, mask-like face 1. L-DOPA
Postural instability: stooped gait c festination 2. MOA-B inhibitors
Postural hypotension: + other autonomic dysfunction
Sleep disorders: insomnia, EDS, OSA, RBD Other therapies
Psychosis: esp. visual hallucinations COMT inhibitor: tolcapone, entacapone
Depression / Dementia / Drug SEs Lessen end-of-dose effect
Apomorphine: potent Da agonist
Sleep Disorder SC rescue pen for sudden off freezing
Affects ~90% of PD pts. Amantidine: weak Da agonist
Insomnia + frequent waking EDS Rx of drug-induced dyskinesias
Inability to turn Atypical antipsychotics: e.g. quetiapine
Restless legs Disease-induced psychosis
Early morning dystonia (drugs wearing off) SSRIs: citalopram, sertraline
Nocturia Depression
OSA
REM Behavioural sleep Disorder Surgical
Loss of muscle atonia during REM sleep Interrupt basal ganglia
Violent enactment of dreams Deep brain stimulation
Da SEs: insomnia, drowsiness, EDS
Autonomic Dysfunction
Combined effects of drugs and neurodegeneration Prognosis
Postural hypotension mortality
Constipation Loss of response to L-DOPA w/i 2-5yrs
Hypersalivation dribbling ( ability to swallow saliva)
Urgency, frequency, Nocturia
ED Differential
Hyperhidrosis Parkinson plus syndromes
Multiple infarcts
L-DOPA SEs: DOPAMINE Drugs: neuroleptics
Dyskinesia Inherited: Wilsons
On-Off phenomena = Motor fluctuations Infection: HIV, syphilis, CJD
Psychosis Dementia pugilistica
ABP
Mouth dryness
Insomnia
N/V
EDS (excessive daytime sleepiness)
Motor Fluctuations
End-of-dose: deterioration as dose wears off c
progressively shorter benefit.
On-Off effect: unpredictable fluctuations in motor
performance unrelated to timing of dose.

Multiple Sclerosis
Definition
A chronic inflammatory condition of the CNS characterised by multiple plaques of demyelination disseminated in time and
space.
Epidemiology Ix
Lifetime risk: 1/1000 MRI: Gd-enhancing or T2 hyper-intense plaques
Age: mean @ onset = 30yrs Gd-enhancing = active inflammation
Sex: F>M = 3:1 Typically located in periventricular white matter
Race: rarer in blacks LP: IgG oligoclonal bands (not present in serum)
Abs
Aetiology Anti-MBP
Genetic (HLA-DRB1), environmental, viral NMO-IgG: highly specific for Devics syn.
Evoked potentials: delayed auditory, visual and sensory
Pathophysiology
CD4 cell-mediated destruction of oligodendrocytes Diagnosis: clinical
demyelination and eventual neuronal death. Demonstration of lesions disseminated in time and space
Initial viral inflam primes humoral Ab responses vs. MBP May use McDonald Criteria
Plaques of demyelination are hallmark
Differential
Classification: Inflammatory conditions may mimic MS plaques:
Relapsing-remitting: 80% CNS sarcoidosis
Secondary progressive SLE
Primary progressive: 10% Devics: Neuromyelitis optica (NMO)
Progressive relapsing MS variant c transverse myelitis and optic atrophy
Distinguished by presence of NMO-IgG Abs
Presentation: TEAM
Tingling Mx
Eye: optic neuritis ( central vision + eye move pain) MDT: neurologist, radiologist, physio, OT, specialist
Ataxia + other cerebellar signs nurses, GP, family
Motor: usually spastic paraparesis
Acute Attack
Clinical features Methylpred 1g IV/PO /24h for 3d
Sensory: Motor Doesnt influence long-term outcome
Dys/paraesthesia Spastic weakness duration and severity of attacks
vibration sense Transverse myelitis
Preventing Relapse: DMARDs
Trigeminal neuralgia
IFN-: relapses by 30% in relapsing remitting MS
Eye: Cerebellum: Glatiramer: similar efficacy to IFN-
Diplopia Trunk and limb ataxia
Visual phenomena Scanning dysarthria Preventing Relapse: Biologicals
Bilateral INO Falls Natalizumab: anti-VLA-4 Ab
Relapses by 2/3 in RRMS
Optic neuritis atrophy
Alemtuzumab (Campath): anti-CD52
nd
GI: Sexual/GU: 2 line in RRMS
Swallowing disorders ED + anorgasmia
Symptomatic
Constipation Retention
Fatigue: modafinil
Incontinence
Depression: SSRI (citalopram)
Lhermittes Sign Pain: amitryptylline, gabapentin
Neck flexion electric shocks in trunk/limbs Spasticity: physio, baclofen, dantrolene, botulinum
Urgency / frequency: oxybutynin, tolterodine
Optic Neuritis ED: sildenafil
PC: pain on eye movement, rapid central vision Tremor: clonazepam
Uhthoffs: vision c heat: hot bath, hot meal, exercise
o/e: acuity, colour vision, white disc, central scotoma, Prognosis
RAPD
Poor Prognostic Signs Better Prognostic Signs
INO / ataxic nystagmus / conjugate gaze palsy Older Female
Disruption of MLF connecting CN6 to CN3 Male <25
Weak adduction of ipsilateral eye Motor signs @ onset Sensory signs @ onset
Nystagmus of contralateral eye Many relapses early on Long interval between
Convergence preserved Many MRI lesions relapses
Axonal loss Few MRI lesions

Cord Compression
Symptoms Cauda Equina and Conus Medullaris Lesions
Deep, local spinal pain Spinal cord tapers to its end at L1
Stabbing, radicular pain in a dermatomal distribution Compared c lesions higher up the cord, these lesions
and LMN weakness @ lesion level are flaccid and areflexic (cf, spastic and hyperreflexic)
Progressive UMN weakness and sensory loss below
lesion Conus Medullaris Lesions
Bladder hesitancy, frequency painless retention Mixed UMN/LMN weakness
Faecal incontinence or constipation Early constipation and retention
Back pain
Signs Sacral sensory disturbance
Look for motor, reflex and sensory level ED
Shooting, radicular pain @ level, anaesthesia below
LMN signs @ level, UMN signs below level Cauda Equina Lesions
Tone and reflexes are usually reduced in acute cord Saddle anaesthesia
compression Back pain
Radicular pain down legs
Causes Bilateral flaccid, areflexic lower limb weakness
Trauma Incontinence / retention of faeces / urine
Infection: epidural abscess, TB Poor anal tone
2O to malignancy: breast, thyroid, bronchus, kidney,
prostate Mx
Disc prolapse As for cord compression
Haematoma: warfarin These are neurosurgical emergencies and require
Intrinsic cord tumour urgent imaging and surgical decompression
Myeloma
Ix
MRI is definitive modality
CXR for primaries
Rx
This is a neurosurgical emergency
Malignancy
Dexamethasone IV
Consider chemo, radio and decompressive
laminectomy
Abscess: abx and surgical decompression
Differential
Transverse myelitis
MS
Cord vasculitis
Spinal artery thrombosis
Aortic dissection

Cervical and Lumbar Degeneration
Spondylosis Lumbosacral Spondylosis
Degeneration due to trauma or ageing
IV disc / vertebral collapse Presentation
Osteophytes L5 and S1 roots most commonly compressed by
May central (myelopathy) and/or lateral prolapse of L4/5, L5/S1 discs.
(radiculopathy) pathology May present as severe pain on sneezing/coughing, a
few days after low back strain
Lumbago low back pain
Cervical Spondylosis Sciatica shooting radicular pain down buttock and
90% of men > 60 and women > 50 thigh
Presentation Signs
Usually asympto Limited spinal flexion
Neck stiffness crepitus Pain on straight-leg raise
Stabbing / dull arm pain (brachialgia)
Upper limb motor and sensory disturbances according L4/5 L5 Root Compression
to compression level (often C7) Weak hallux extension foot drop
Can myelopathy c quadraparesis and sphincter In foot drop due to L5 radiculopathy, weak
dysfunction inversion (tib. post.) helps distinguish from
peroneal N. palsy.
Specific Signs sensation on inner dorsum of foot
Lhermittes sign: neck flexion tingling down spine
Hoffman reflex: flick to middle finger pulp brief pincer L5/S1 S1 Root Compression
flexion of thumb and index finger Weak foot plantarflexion and eversion
Loss of ankle-jerk
Typical Deficits Calf pain
sensation over sole of foot and back of calf
Root Disc Motor Weakness Sensory
C5 C4/5 Deltoid Numb elbow Central Compression
Supraspinatus Cauda equina syndrome
supinator jerk
C6 C5/6 Biceps Numb thumb and index Ix
Brachioradialis finger MRI is definitive (emergency if cauda-equina syndrome)
biceps jerk
C7 C6/7 Triceps Numb middle finger Rx
Finger extension Conservative: rest, analgesia, mobilisation/physio
triceps jerk Medical: transforaminal steroid injection
C8 C7/T1 Finger flexors Number ring and little Surgical: discectomy or laminectomy may be
Intrinsic hand fingers considered in cauda-equina syndrome, continuing pain
or muscle weakness.
Ix
MRI
Spinal Stenosis
Rx Developmental predisposition facet joint osteoarthritis
Conservative: stiff collar, analgesia generalized narrowing of lumbar spinal canal.
Medical: transforaminal steroid injection
Surgical: decompression: laminectomy or laminoplasty Presentation
Spinal claudication
Differential Aching or heavy buttock and lower limb pain on
MS walking
Nerve root neurofibroma Rapid onset
SACD May c/o paraesthesiae/numbness
Pain eased by leaning forward (e.g. on bike)
Pain on spine extension
Negative straight leg raise
Ix
MRI
Rx
Corsets
NSAIDs
Epidural steroid injection
Canal decompression surgery

Facial Nerve Palsy
Bells Palsy Other Causes of Facial Palsy
Inflammatory oedema from entrapment of CNVII in
narrow facial canal May be suggested by
Probably of viral origin (HSV1) Bilat symptoms: Lyme, GBS, leukaemia, sarcoid, MG
75% of facial palsy UMN signs: sparing of frontalis and orbicularis oculi
Due to bilateral cortical representation
Features Other CN palsies (but seen in 8% of Bells)
Sudden onset: e.g. overnight Limb weakness
Complete, unilateral facial weakness in 24-72h Rashes
Failure of eye closure dryness
Bells sign: eyeball rolls up on attempted closure Intracranial
Drooling, speech difficulty Vascular, MS, SOL
Numbness or pain around ear Motor cortex UMN
taste (ageusia) Assoc. c ipsilateral hemiplegia
Hyperacusis: stapedius palsy Brainstem nuclei LMN
Usually assoc. c CN6 palsy + contralateral
Ix hemiplegia
Serology: Borrelia or VZV Abs Cerebello-pontine angle: acoustic neuroma, meningioma
MRI: SOL, stroke, MS th th
Both may be accompanied by 5 , 6 and 8 CN
th
LP palsies and cerebellar signs

Loss of corneal reflex
Mx Sensorineural deafness, tinnitus, vertigo
Give prednisolone w/i 72hrs DANISH
60mg/d PO for 5/7 followed by tapering
Valaciclovir if zoster suspected Intra-temporal
Otherwise antivirals dont help Cholesteatoma
Protect eye Ramsay Hunt
Dark glasses Otitis media
Artificial tears Trauma
Tape closed @ night
Plastic surgery may help if no recovery Infra-temporal
Parotid tumours
Prognosis Trauma
Incomplete paralysis: recovers completely w/i wks
Complete: 80% get full recovery Systemic
Remainder have delayed recovery or permanent Peripheral neuropathy
neurological / cosmetic abnormalities. Demyelinating: GBS
Axonal: DM, Lyme, HIV, Sarcoid
Complications: Aberrant Neural Connections Pseudopalsy: MG, botulism
Synkinesis: e.g. blinking causes up-turning of mouth
Crocodile tears: eating stimulates unilateral
lacrimation, not salivation
Ramsay Hunt Syndrome

American neurologist James Ramsay Hunt in 1907
Reactivation of VZV in geniculate ganglion of CNVII
Features
Preceding ear pain or stiff neck
Vesicular rash in auditory canal TM, pinna, tongue,
hard palate (no rash = zoster sine herpete)
Ipsilateral facial weakness, ageusia, hyperacusis,
May affect CN8 vertigo, tinnitus, deafness
Mx
If Dx suspected give valaciclovir and prednisolone w/i
first 72h
Prognosis
Rxed w/i 72h: 75% recovery
Otherwise: 1/3 full recovery, 1/3 partial, 1/3 poor

Mononeuropathies
Lesions of individual peripheral or cranial nerves
Usually local cause: trauma, entrapment
Mononeuritis multiplex: 2 or more peripheral nerves affects
Usually systemic cause: DM most commonly
WAARDS PLC: Wegeners, AIDS, Amyloid, RA, DM, Sarcoidosis, PAN, Leprosy, Carcinomatosis
Electromyography (EMG) helps define site of lesion
Nerve Location / Cause Motor Features Sensory Loss/ Features

Median: C6-T1 Wrist: carpal tunnel, trauma LLOAF muscles Radial 3 fingers and palm
Thenar wasting Aching pain in hand
2-point discrimination
Tinels and Phalens +ve
Ulnar: C7-T1 Elbow trauma Partial claw hand Ulnar 1 fingers
- e.g. supracondylar # Hypothenar wasting
Cant do good luck sign
Weakness and wasting of 1st dorsal
interosseous
Froments +ve
Radial: C5-T1 Low: wrist Low: finger drop Dorsal thumb root (snuff box)
High: humerus High: wrist drop
V. high: Axilla V. high: triceps paralysis, wrist drop
Brachial plexus Trauma High (C5-6): Erbs palsy waiters tip High: C5-6 dermatome
Radiotherapy (e.g. breast) Low (C8-T1): Klumpkes claw hand Low: C8-T1 dermatome
Phrenic: C3-5 Neoplastic: Orthopnoea + raised hemidiaphragm
Lung Ca
Myeloma
Thymoma
Mechanical:
Cervical spondylosis
Big left atrium
Infective:
C3-5 zoster
HIV
Lyme
TB
Lat. cut. N. Entrapment under inguinal Meralgia paraesthetica
thigh: L2-3 ligament anterolat. burning thigh pain
Sciatic: L4-S3 Pelvic tumours Hamstrings Below knee laterally and foot
Pelvic or femur #s All muscles below knee
Common Fibular head: trauma, sitting Foot drop: cant walk on heals Below knee laterally
peroneal: L4-S1 cross legged Weak ankle dorsiflexion, eversion
NB. inversion intact!
Tibial: L4-S3 Cant plantar flex cant stand on tiptoe Sole of foot
Foot inversion
Toe flexion

Polyneuropathies
Features Sensory Neuropathy
Generalised disorders of peripheral or cranial nerves
Distribution is symmetrical and widespread Main Causes
Distal weakness and sensory loss (glove + stocking) Alcohol
Classification B12
Time-course: acute, chronic CRF and Ca (paraneoplastic)
Function: motor, sensory, autonomic, mixed DM
Path: demyelination, axonal degeneration, both Every vasculitis
General Features
Causes Glove and stocking distribution: length dependent
Deep tendon reflexes may be or absent
Metabolic (mostly axonal) Vasculitis E.g. loss of ankle jerks in diabetic neuropathy
DM PAN Signs of trauma or joint deformity (Charcots joints)
Renal failure / uraemia RA Diabetic and alcoholic neuropathies are painful
Hypothyroid Wegeners Some aetiologies favour loss of particular fibres
B1 or B12 (EtOH)
Large Myelinated Fibres (A): e.g. B12
Inflammatory Infection Loss of proprioception ataxia
GBS HIV Pins and needles
Sarcoidosis Syphilis
Leprosy Small Unmyelinated Fibres (C): e.g. EtOH
Lyme Loss of pain and temperature sensation
Painful dysesthesia: e.g. burning, hyperalgesia
Inherited Toxins
CMT Lead
Refsums syndrome Motor Neuropathy
Main Causes
Drugs Other GBS (+ botulism)
Isoniazid Amyloid HMSN / CMT
EtOH Paraproteinaemias Paraneoplastic
Phenytoin Lead poisoning
Vincristine
Features
Weakness/clumsiness of hands, difficulty walking
History LMN signs
Time-course CN: diplopia, dysarthria, dysphagia
Precise symptoms Involvement of respiratory muscles FVC
Assoc. events
D&V: GBS
wt: Ca
Arthralgia: connective tissue
Autonomic Neuropathy
Travel, EtOH, drugs
Causes
DM
HIV
Ix
SLE
LFTs, U+E, glucose, ESR, B12
GBS, LEMS
TFTs B1, ANA, ANCA
Genetic tests: e.g. PMP22 in CMT
Features
Nerve conduction studies Postural hypotension
EMG ED, ejaculatory failure
sweating
Constipation / Nocturnal diarrhoea
Urinary retention
Horners
Autonomic Function Tests

BP: Postural drop > 20/10mmHg
ECG: variation >10bpm c respiration
Primary Autonomic Failure

Idiopathic or part of MSA or PD

Guillain-Barr Syndrome Charcot-Marie-Tooth Syndrome
= Peroneal Muscular Atrophy
Classification = Hereditary Motor and Sensory Neuropathy
AIDP: Acute autoimmune demyelinating polyneuropathy
AMAN: Acute motor ( sensory) axonal neuropathy Pathophysiology
Miller-Fisher: Ophthalmoplegia + ataxia + areflexia Group of inherited motor and sensory neuropathies
Causes HMSN1
Abs cross-react to gangliosides Commonest form
No precipitant identified in 40% Demyelinating
Bacteria: C. jejuni, mycoplasma AD mutation in the peripheral myelin protein 22 gene
Viruses: CMV, EBV, HSV, HIV, flu
Vaccines: esp. rabies HMSN2
Second commonest form
Axonal degeneration (near normal conduction velocity)
Features and Ix: GBS=AIDP
Growing Weakness Clinical Features
Symmetrical, ascending flaccid weakness / paralysis Onset at puberty
LMN signs: areflexia, fasciculations may occur
Proximal > distal (trunk, respiratory, CNs [esp. 7]) Nerves
Progressive phase lasts 4wks Thickened, enlarged nerves: esp. common peroneal
Breathing and Bulbar Problems Motor

Foot drop high stepping gait
Back Pain Weak ankle dorsiflexion and toe extension
Back / limb pain is common Absent ankle jerks
Symmetrical muscle atrophy: mainly distal
Sensory disturbance Peroneal muscles Champagne Bottle
Paraesthesia in extremities Hand and arm muscles Claw Hand
Sensory ataxia in Miller-Fisher Pes cavus (high-arched feet)
Autonomic Neuropathy Sensory

Arrhythmias, HR Variable loss of sensation in a stocking distribution
Labile BP Neuropathic pain in some
Sweating
Urinary retention Ix
Genetic tests: PMP22 gene mutation
Immune Nerve conduction studies: conduction speed in CMT1
Serology for anti-ganglioside Abs
Evidence of infection: e.g. stool sample Mx
Supportive
Demyelinating Nerve Conduction Studies Physio
Slow conduction velocities Podiatry
Orthoses: e.g. ankle braces
Protein in CSF
Protein often > 5.5g/L
Normal white cell count
Mx
Supportive
Airway / ventilation: ITU if FVC < 1.5L
Analgesia: NSAIDs, gabapentin
Autonomic: may need inotropes, catheter
Antithrombotic: TEDS, LMWH
Immunosuppression
IVIg
Plasma exchange
Physiotherapy
Prevent flexion contractures
Prognosis
85% complete recovery
10% unable to walk alone at 1yr
5% mortality
Motor Neurone Disease
Characteristics Classification
Cluster of degenerative disease characterised by
axonal degeneration of neurones in the motor cortex, Amyotrophic Lateral Sclerosis: 50%
CN nuclei and anterior horn cells. Loss of motor neurones in cortex and anterior horn
UM and LM neurones affected (cf. polyneuropathy) UMN signs and LMN wasting + fasciculation
No sensory loss or sphincter disturbance (cf. MS)
Never affects eye movements (cf. MG) Progressive Bulbar Palsy: 10%
Only affects CN 9-12 bulbar palsy
Epidemiology
Prevalence: 6/100,000 Progressive Muscular Atrophy: 10%
Sex: M>F=3:2 Anterior horn cell lesion LMN signs only
Median age @ onset = 60yrs Distal to proximal
Often fatal in 2-4yrs Better prognosis cf. ALS
Primary Lateral Sclerosis

Causes Loss of Betz cells in motor cortex mainly UMN signs
Unknown
Marked spastic leg weakness and pseudobulbar palsy
~10% familial: SOD1 mutation in 20% of those
No cognitive decline
Ix
Brain/cord MRI: exclude structural cause
Cervical cord compression myelopathy Bulbar Palsy
Brainstem lesions Diseases of nuclei of CN 9-12 in the medulla
LP: exclude inflammatory cause LMN lesions of tongue, talking and swallowing
EMG: shows denervation Signs
Flaccid, fasciculating tongue
Speech: quiet or nasal (Donald Duck speech)
Features Normal / absent jaw jerk
UMN: spasticity, reflexes, plantars Loss of gag reflex
LMN: wasting, fasciculation of tongue / abdo / thigh Causes
Speech or swallowing impairment MND
Fronto-temporal dementia GBS
MG
Diagnosis Central pontine myelinolysis (CPM)
MRI to exclude structural lesions
LP to exclude inflammation
EMG shows acute denervation Pseudobulbar / Corticobulbar Palsy
Use Revised El Escorial Diagnostic Criteria Commoner than bulbar palsy
Bilateral lesions above mid-pons (e.g. corticobulbar
Mx tracts) UMN lesions of swallowing and talking
MDT: neurologist, physio, OT, dietician, specialist CN motor nuclei have bilateral cortical
nurse, GP, family representation except lower half of CN7
Discussion of end-of-life decisions Signs
E.g. Advanced directive Spastic tongue
DNAR Slow tongue movements c slow deliberate
speech: hot-potato speech
Specific Brisk jaw jerk
Riluzole: antiglutamatergic that prolongs life by ~3mo Emotional incontinence
Causes
Supportive MS
Drooling: propantheline or amitriptyline MND
Dysphagia: NG or PEG feeding Stroke
Respiratory failure: NIV CPM
Pain: analgesic ladder
Spasticity: baclofen, botulinum
Prognosis Polio
Most die w/i 3yrs RNA virus
Bronchopneumonia and respiratory failure Affects anterior horn cells
Worse prog: elderly, female, bulbar involvement Fever, sore throat, myalgia
0.1% develop paralytic polio
Asymmetric LMN paralysis
No sensory involvement
May be confined to upper or lower limbs or both
Respiratory muscle paralysis can death

Myopathies
Myopathy vs. Neuropathy Myotonic Dystrophy
Myopathy AD Cl- channelopathy
Gradual onset Onset in 20s
Symmetrical, proximal weakness: difficulty combing Tonic muscle spasm (myotonia)
hair, climbing stairs, getting up from chairs
Dystrophies usually affect specific muscle groups Presentation
Preserved tendon reflexes Face
Myopathic facies: long, thin, expressionless
Neuropathy Wasting of facial muscles and SCM
Paraesthesia, bladder problems Bilateral ptosis
Distal weakness Dysarthria: myotonia of tongue and pharynx
Hands
Other Pointers Myotonia: slow relaxation
Rapid onset: neuropathy, or drug, toxic or metabolic E.g. inability to release hand after shake
myopathy Wasting and weakness of distal muscles +
Fatiguability: MG, LEMS areflexia wrist drop
Spontaneous pain and tenderness @ rest: inflam Percussion myotonia: percuss thenar eminence
myopathy involuntary thumb flexion
Pain on exercise: ischaemia or metabolic myopathy Other
Oddly firm muscles: pseudohypertrophy in muscular Frontal balding
dystrophies Cataracts
Fasciculation: anterior horn cell or root disease DM
Cardiomyopathy, tachy- / brad-arrhythmias
Dysphagia
Ix
Testicular atrophy
ESR, CK, AST, LDH
EMG Rx
No Rx for weakness
Phenytoin may improve myotonia
Muscular Dystrophies Caution
c GA: high risk of anaesthetic complications
Group of genetic disease
c progressive degeneration
and weakness of specific muscle groups. Prognosis
Most die in middle-age of intercurrent illness
DMD
Commonest: 3/1000 male births
X-linked recessive, 30% spontaneous non-functional Acquired myopathies of late onset
dystrophin
Usually part of systemic disease
Presentation
Hyperthyroidism, Cushings, /Ca2+
~4yrs old
Difficulty standing Drugs: steroids, statins, EtOH
Calf pseudohypertrophy
Respiratory failure
Ix: CK Inflammatory Myopathies
Prog: some survive > 20yrs Inclusion body myositis
Polymyositis
BMD Dermatomyositis
0.3/1000 male births
X-linked recessive Inclusion Body Myositis
Partially functioning dystrophin Asymmetric weakness affecting distal and prox muscles
Presents later, is less severe and has better prognosis Early involvement of quads, ankle dorsiflexors
and wrist/finger flexors
Facioscapulohumeral MD (Landouzy-Dejerine) loss of grip strength and dexterity
Almost as common as DMD Dysphagia is very common
AD inheritance Myalgia is relatively uncommon
Presentation
Onset @ 12-14yrs
Difficulty puffing cheeks and raising arms above
head
Signs
Weakness of face, shoulders and upper arms
(often asymmetric c deltoids spared)
Winging of scapula
Foot drop.
Prog: <20% need wheelchair by 20yrs

Myasthenia Gravis
Pathophysiology Associations
Autoimmune disease mediated by Abs vs. nicotinic Ach <50yrs MG is commoner in women and assoc. c other
receptors. AI disease (DM, RA, Graves) and thymic hyperplasia.
Interferes
c NM transmission via depletion of working >50yrs MG is commoner in men and assoc. c thymic
post-synaptic receptor sites atrophy or thymic tumour.
Presentation Treatment
ing muscular fatigue
Extra-ocular: bilateral ptosis, diplopia Symptom Control
Bulbar: voice deteriorates on counting to 50 Anticholinesterase: e.g. pyridostigmine.
Face: myasthenic snarl on attempting to smile Cholinergic SEs = SLUDGEM
Neck: head droop
Limb: asymmetric, prox. weakness Immunosuppression
Normal tendon reflexes Rx relapses
c pred
Weakness worsened by pregnancy, infection, emotion, Steroids may be combined
c azathioprine or
drugs (-B, gent, opiates, tetracyclines) methotrexate
Investigations Thymectomy
Tensilon Test Consider if young onset and disease not control by
Give edrophonium IV anticholinesterases
+ve if power improves w/i 1min Remission in 25%, benefit in further 50%.
Anti-AChR Abs: in 90%, MuSK Abs
EMG: response to a train of impulses Complications
Respiratory function: FVC
Thymus CT Myasthenic Crisis
TFTs Weakness of respiratory muscles during relapse may
be lethal.
Differential of Muscle Fatigability Monitor FVC: vent support if <20ml/kg
Polymyositis Plasmapheresis or IVIg
SLE Rx trigger for relapse (drugs, infection)
Botulism
Prognosis
Relapsing or slow progression
Lambert-Eaton Myasthenic Syndrome (LEMS)

Pathophysiology
Abs to VGCC influx of Ca2+ during presynaptic excitation
presynaptic ACh-vesicle fusion.
Causes
Paraneoplastic: e.g SCLC
Autoimmune
Presentation
As for MG except: LEMS
Leg weakness early (before eyes)
Extra: Autonomic and areflexia
Movement improves symptoms
Small response to edrophonium
Anti-VGCC Abs
Mx
3,4-diaminopyridine or IVIg
Do regular CXRs / HRCTs as symptoms my precede Ca by 4yrs
Botulism
Botulinum toxin prevents ACh vesicle release
Descending flaccid paralysis c no sensory signs
Anti-cholinergic effects: mydriasis, cycloplegia, n/v, dry mouth, constipation
Rx: benpen + antiserum
Neurofibromatosis 1 von Neurofibromatosis 2
Recklinghausens
Epidemiology
Epidemiology AD inheritance (Chr 22), but 50% are de novo
Prev: 1/35,000
AD Chr 17
Variable expression
Prev: 1/2500 Signs
Caf-au-lait spots
Features: CAF NOIR
Rare
Fewer cf. NF1
Caf-au-lait spots
1st yr of life
Bilateral Vestibular Schwannomas
in size and no.
c age
Characteristic
Adults: >6, >15mm across Symptomatic by 20yrs
SNHL is first sign, then tinnitus, vertigo
Axillary Freckling
in skin folds Juvenile Posterior Subcapsular Lenticular Opacity
Form of cataract
Fibromas, neuro-:
Bilateral
Subcutaneous
Occur before other manifestations and may be useful
Small, gelatinous, violaceous nodules
for screening those @ risk
Appear @ puberty
May itch
Nos. c age Complications
Plexiform Tender schwannomas of cranial and peripheral nerves
Overgrowth of nerve trunk and overlying tissue and spinal nerve roots.
Large cutaneous mass Meningiomas: often multiple
Complications Gliomas
Sarcomatous change
Compression: Mx
Nerve roots: weakness, pain, paraesthesia Hearing tests from puberty in affected families
GI: bleeds and obstruction MRI brain if abnormality detected
Eye Prognosis
Lisch nodules Mean survival from Dx is 15yrs
Brown/translucent iris hamartomas
Use a slit lamp
Optic N. glioma
Neoplasia
CNS: meningioma, ependyoma, astrocytoma
Phaeochromocytoma
Chronic or acute myeloid leukaemia
Orthopaedic
Kyphoscoliosis
Sphenoid dysplasia
IQ and Epilepsy
Renal
RAS BP
Mx
MDT orchestrated by GP
Yearly BP and cutaneous review
Excise some neurofibromas
Genetic counselling
Caf-au-Lait Spots Differential

NF
McCune-Albright
Multiple Lentigenes
Urticaria Pigmentosa

Intrinsic Cord Disease Syringomyelia
Presentation Characteristics
Painless Syrinx: tubular cavity in central canal of the cervical cord.
Early sphincter / erectile dysfunction Onset @ 30yrs
Bilateral motor and sensory disturbance below Symptoms may be static for yrs but then worsen fast
lesion e.g. on coughing, sneezing as pressure extension
Commonly located in cervical cord
Causes: DIVINITY Syrinx expands ventrally affecting:
Decussating spinothalamic neurones
Degenerative Anterior horn cells
MND Corticospinal tracts
Developmental Causes
Friedrichs Ataxia Blocked CSF circulation c flow from posterior fossa
Hereditary spastic paraparesis Arnold-Chiari malformation (cerebellum herniates
through foramen magnum)
Infection Masses
Viral: HIV, HTLV-1 Spina bifida
Syphilis: Tabes Dorsalis 2O to cord trauma, myelitis, cord tumours and AVMs
Vascular Infarction Cardinal Signs

Aortic dissection/aneurysm 1. Dissociated Sensory Loss
Thromboembolism Absent pain and temperature scars from burns
Atheroma Preserved touch, proprioception and vibration.
Vasculitis: esp. PAN Root distribution reflects syrinx location
Usually upper limbs and chest: cape
NB. ant. spinal A. infarction spinothalamic and 2. Wasting/weakness of hands Claw hand
corticospinal tract loss bilat loss of pain/temp and 3. Loss of reflexes in upper limb
spastic paresis 4. Charcot Joints: shoulder and elbow
= Becks Syndrome
Other Signs
Inflammation UMN weakness in lower limbs c upgoing plantars
Demyelination: MS
Horners syndrome
Transverse myelitis
Syringobulbia: cerebellar and lower CN signs
Kyphoscoliosis
Neoplasia
Glioma
Ependymoma
Ix
MRI spine
Injury
Surgery
Toxin / Nutrition Decompression at the foramen magnum for Chiari mal
B12 deficiency
sYringomyelia
Brown-Sequard Syndrome
Hemi-cord lesion
Ipsilateral loss of proprioception and vibration
sense
Ipsilateral UMN weakness
Contralateral loss of pain sensation

Miscellaneous Conditions
Friedrichs Ataxia
Auto recessive progressive degeneration of DRGs,
spinocerebellar and corticospinal tracts and
cerebellar cells
Mitochondrial disorder
Onset in teenage years
Assoc.
c HOCM and mild dementia
Presentation
Pes cavus and scoliosis
Bilateral cerebellar signs
Ataxia
Dysarthria
Nystagmus
Leg wasting + areflexia but extensor plantars
Loss of lower limb proprioception and vibration
sense
Optic atrophy
th
Cardiac: HOCM ESM + 4 heart sound
DM hyperglycaemia
Hereditary Spastic Paraparesis

Lower limb spasticity
Ataxia
Extrapyramidal signs
Human T-lymphotropic Virus-1

Retrovirus
prevalence in Japan and Caribbean
Features
Adult T cell leukaemia / lymphoma
Tropical spastic paraplegia / HTLV myelopathy
Slowly progressing spastic paraplegia
Sensory loss and paraesthesia
Bladder dysfunction

Rheumatology
Contents
Patterns of Presentation ............................................................................................................................................................ 199
Rheumatological Investigations................................................................................................................................................. 199
Back Pain .................................................................................................................................................................................. 200
Osteoarthritis ............................................................................................................................................................................. 201
Septic Arthritis ........................................................................................................................................................................... 201
Rheumatoid Arthritis .................................................................................................................................................................. 202
Gout ........................................................................................................................................................................................... 203
Ca Pyrophosphate Dehydrate Arthropathy ............................................................................................................................... 203
Seronegative Spondyloarthropathies ........................................................................................................................................ 204
Autoimmune Connective Tissue Disease ................................................................................................................................. 205
Systemic Sclerosis .................................................................................................................................................................... 206
Polymyositis and Dermatomyositis............................................................................................................................................ 206
Systemic Lupus Erythematosus ................................................................................................................................................ 207
Vasculitis ................................................................................................................................................................................... 208
ANCA Positive Vasculitidies ...................................................................................................................................................... 209
ANCA Negative Vasculitidies .................................................................................................................................................... 209
Fibromyalgia .............................................................................................................................................................................. 210

Patterns of Presentation Rheumatological Investigations
Monoarthritis Joint Aspiration
Septic arthritis The key investigation in a monoarthritis
Crystal arthritis: gout, CPPD Appearance
Osteoarthritis Send for
Trauma: haemarthrosis WCC
Gram stain and culture
Oligoarthritis (5 joints) Polarized light microscopy
Crystal arthritis
Psoriatic arthritis
Reactive arthritis Bloods
Ankylosing spondylitis Basic: FBC, U+E, ESR, CRP, urate
Osteoarthritis Culture: septic arthritis
Abs: RF, ANA, others
Polyarthritis (>5 joints) HLA-B27
Viral serology, urine chlamydia PCR: reactive arthritis
Symmetrical
RA
Osteoarthritis Radiology
Viruses: Hep A,B,C, mumps CXR: RA, SLE, Vasculitis, TB, Sarcoid
US/MRI: more sensitive for synovitis, enthesitis, infection
Asymmetrical
Reactive arthritis Osteoarthritis
Psoriatic arthritis Loss of joint space
Osteophytes
Either Subchondral cysts
Systemic disease: SLE, sarcoid, endocarditis Subchondral sclerosis
Rheumatoid Arthritis
Loss of joint space
Soft tissue swelling
Peri-articular osteopenia
Deformity
Subluxation
Gout
Normal joint space
Soft tissue swelling
Periarticular erosions

Back Pain
Red Flags Ix
Age <20 or >55yrs Usually only necessary if red flags present
Neurological disturbance (inc. sciatica) FBC, ESR, CRP, ALP, se electrophoresis, PSA
Sphincter disturbance MRI
Bilateral or alternating leg pain
Current or recent infection Mx
Fever, wt. loss, night sweats Neurosurgical referral if neurology
History of malignancy Conservative
Thoracic back pain Max 2d bed rest
Morning stiffness Education: keep active, how to lift / stoop
Acute onset in elderly people Physiotherapy
Constant or progressive pain Psychosocial issues re. chronic pain and disability
Nocturnal pain Warmth
Medical
Analgesia: paracetamol NSAIDs codeine
Muscle relaxant: low-dose diazepam (short-term)
Causes Facet joint injections
Mechanical
Surgical
Strain/idiopathic
Decompression
Trauma
Prolapse surgery: e.g. microdiscectomy
Pregnancy
Disc prolapse
Spondylolisthesis (forward shift of one vertebra)
Degenerative: spondylosis, vertebral collapse, stenosis Neurosurgical Emergencies
Inflammatory: Ank spond, Pagets
Neoplasm: Mets, myeloma Acute Cord Compression
Infection: TB, abscess Bilateral pain: back and radicular
LMN signs at compression level
UMN signs and sensory level below compression
Sphincter disturbance
Nerve Root Lesions
Acute Cauda Equina Compression
Root Weakness Reflex
Alternating or bilateral radicular pain in the legs
L2 Hip flexion + adduction
Saddle anaesthesia
L3 Knee extension Knee Jerk
Loss of anal tone
Hip adduction
Bladder bowel incontinence
L4 Foot inversion + dorsiflexion Knee Jerk
Knee extension
Rx
L5 Great toe dorsiflexion
Large prolapse: laminectomy / discectomy
Foot inversion + dorsiflexion
Knee Flexion Tumours: radiotherapy and steroids
Hip extension + abduction Abscesses: decompression
S1 Foot eversion Ankle Jerk
Foot and toe plantarflexion
Knee flexion

Osteoarthritis Septic Arthritis
Definition Pathophysiology
Degenerative joint disorder in which there is Source: local or haematogenous.
progressive loss of hyaline cartilage. Organisms
Staph: commonest overall (60%)
Aetiology / Risk Factors Gonococcus: commonest in young sexually active
Age (80% > 75yrs) Streps
Obesity Gm-ve bacilli
Joint abnormality RFs
Joint disease (e.g. RA)
Classification CRF
Immunosuppression (e.g. DM)
Primary: no underlying cause
Prosthetic joints
Secondary: obesity, joint abnormality
Symptoms
Symptoms
Acutely inflamed tender, swollen joint
Affects: knees, hips, DIPs, PIPs, thumb CMC
ROM
Pain: worse c movement, background rest/night pain,
Systemically unwell
worse @ end of day.
Stiffness: especially after rest, lasts ~30min (e.g. AM)
Investigations
Deformity
Joint aspiration for MCS
ROM
WCC (e.g. >50,000/mm3): mostly PMN
ESR/CRP, WCC, Blood cultures
Signs X-ray
Bouchards (prox), Heberdens (dist.) nodes
Thumb CMC squaring
Management
Fixed flexion deformity
IV Abx: vanc + cefotaxime
Consider joint washout under GA
Hx and Ix Splint joint
Focus on ADLs and social circumstances
Physiotherapy after infection resolved
X-ray
Complications
Differential Osteomyelitis
Septic
Arthritis
Crystal
Ankylosis: fusion
Trauma
Differential
Mx Crystal arthropathy
Reactive arthritis
Conservative
wt.
Alter activities: rest, sport
Physio: muscle strengthening
Walking aids, supportive footwear, home mods
Medical
Analgesia
Paracetamol
NSAIDs: e.g. arthrotec (diclofenac + misoprostol)
But misoprostol diarrhoea
Tramol
Joint injection: local anaesthetic and steroids
Surgical
Arthroscopic washout: esp. knee.
Trim cartilage, remove foreign bodies.
Arthroplasty: replacement (or excision)
Osteotomy: small area of bone cut out.
Arthrodesis: last resort for pain management
Novel Techniques
Microfracture: stem cell release fibro-cartilage
formation
Autologous chondrocyte implantation

Rheumatoid Arthritis
Definition Ix
Chronic systemic inflammatory disease characterised by Bloods: FBC (anaemia, PMN, plat), ESR, CRP
a symmetrical, deforming, peripheral polyarthritis. RF +ve in 70%
High titre assoc. c severe disease, erosions and
Epidemiology extra-articular disease
Prev: 1% ( in smokers) -ve = seronegative rheumatoid
Sex: F>M=2:1 Anti-CCP: 98% specific (Ag derived from collagen)
Age: 5th-6th decade ANA: +ve in 30%
Genetics: HLA-DR4/DR1 linked Radiography, US, MRI
Features: ANTI CCP Or RF Mx

Conservative
Arthritis Refer to rheumatologist
Symmetrical, polyarthritis of MCPs, PIPs of hands and Regular exercise
feet pain, swelling, deformity PT
1. Swan neck OT: aids, splints
2. Boutonniere Medical
3. Z-thumb DAS28: Monitor disease activity
4. Ulnar deviation of the fingers DMARDs and biologicals: use early
5. Dorsal subluxation of ulnar styloid Steroids: IM, PO or intra-articular for exacerbations
Morning stiffness >1h Avoid giving until seen by rheumatologist
Improves c exercise NSAIDs: good for symptom relief
Larger joints may become involved Mx CV risk: RA accelerates atherosclerosis
Prevent osteoporosis and gastric ulcers
Nodules Surgical
Commonly elbows also fingers, feet, heal Ulna stylectomy
Firm, non-tender, mobile or fixed Joint prosthesis
Lungs
DMARDs
Tenosynovitis 1st line for treating RA
De Quervains Early DMARD use assoc. c better long-term outcome
Atlanto-axial subluxation
All DMARDs can myelosuppression pancytopenia
Immune
Main agents
AIHA
Methorexate: hepatotoxic, pulmonary fibrosis
Vasculitis
Sulfasalazine: hepatotoxic, SJS, sperm count
Amyloid
Hydroxychloroquine: retinopathy, seizures
Lymphadenopathy
Other Agents
Leflunomide: risk of infection and malignancy
Cardiac: pericarditis + pericardial effusion
Gold: nephrotic syndrome
Carpal Tunnel Syndrome Penicillamine: drug-induced lupus, taste change
Pulmonary Biologicals
Fibrosing alveolitis (lower zones) Anti-TNF
Pleural effusions (exudates) Severe RA not responding to DMARDs
Screen and Rx TB first
Ophthalmic Infliximab: chimeric anti-TNF Ab
Epi-/scleritis Etanercept: TNF-receptor
O
2 Sjogrens Syndrome Adalimumab: human anti-TNF Ab
SEs: infection (sepsis, TB), AI disease, Ca
Raynauds
Rituximab (anti-CD20 mAb)
Feltys Syndrome severe RA not responding to anti-TNF therapy
RA + splenomegaly + neutropenia
Splenomegaly alone in 5%, Feltys in 1% Anatomy of Rheumatoid Hands
Boutonierres: rupture of central slip of extensor
Dx 4/7 of: expansion PIPJ prolapse through button-hole
1. Morning stiffness >1h (lasting >6wks) created by the two lateral slips.
2. Arthritis 3 joints Swan: rupture of lateral slips PIPJ hyper-extension
3. Arthritis of hand joints
4. Symmetrical Differential of Rheumatoid Hands
5. Rheumatoid nodules
Psoriatic arthritis: nail changes and plaques
6. +ve RF
Jaccouds arthropathy: reducible in extension
7. Radiographic changes
Chronic crystal arthritis
Gout Ca Pyrophosphate Dehydrate
Arthropathy
Pathophysiology Pseudogout / Chondrocalcinosis
Deposition of monosodium urate crystals in and around
joints erosive arthritis
May be ppted by surgery, infection, fasting or diuretics Acute CPPD
Presents as acute monoarthropathy
Presentation Usually knee, wrist or hip
M>F=5:1 Usually spontaneous and self-limiting
Acute monoarthritis c severe joint inflammation
~60% occur @ great toe MTP = Podagra
Also: ankle, foot, hand joints, wrist, elbow, knee Chronic CPPD
Also: asymmetric oligoarthritis Destructive changes like OA
Urate deposits in pinna and tendons = Tophi Can present as poly-arthritis (pseudo-rheumatoid)
Renal disease: radiolucent stones and interstitial
nephritis
Risk Factors
Differential age
Septic arthritis OA
Pseudogout DM
Haemarthrosis Hypothyroidism
Hyperparathyroidism
Causes Hereditary haemochromatosis
Hereditary Wilsons disease
Drugs: diuretics, NSAIDs, cytotoxics, pyrazinamide
excretion: 1O gout, renal impairment
cell turnover: lymphoma, leukaemia, psoriasis, Ix
haemolysis, tumour lysis syndrome Polarized light microscopy
EtOH excess Positively birefringent rhomboid-shaped crystals
Purine rich foods: beef, pork, lamb, seafood X-ray may show chondrocalcinosis
Soft-tissue Ca deposition (e.g. knee cartilage)
Associations
Check for:
HTN Rx
IHD Analgesia
Metabolic syndrome NSAIDs
May try steroids: PO, IM or intra-articular
Ix
Polarised light microscopy
Negatively birefringent needle-shaped crystals
serum urate (may be normal)
X-ray changes occur late
Punched-out erosions in juxta-articular bone
joint space
Acute Rx
NSAID: diclofenac or indomethacin
Colchicine
NSAIDs CI: warfarin, PUD, HF, CRF
SE: diarrhoea
In renal impairment: NSAIDs and colchicine are CI
Use steroids
Prevention
Conservative
Lose wt.
Avoid prolonged fasts and EtOH excess
Xanthine Oxidase Inhibitors: Allopurinol
Use if recurrent attacks, tophi or renal stones
Introduce
c NSAID or colchicine cover for 3/12
SE: rash, fever, WCC (c azathioprine)
Use febuxostat (XO inhibitor) if hypersensitivity
Uricosuric drugs: e.g. probenecid, losartan
Rarely used
Recombinant urate oxidase: rasburicase
May be used pre-cytotoxic therapy
Seronegative Spondyloarthropathies
Definition Psoriatic Arthritis
Group of inflammatory arthritidies affecting the spine and Develops in 10-40% and may predate skin disease
peripheral joints w/o production of RFs and associated
c HLA-B27 allele.
Patterns of joint involvement
Asymmetrical oligoarthritis: 60% (commonest)
Distal arthritis of the DIP joints: 15% (classical)
Common Features Symmetrical polyarthritis: 15% (like RA but c DIPJs)
Axial arthritis and sacroiliitis Arthritis mutilans (rare, ~3%)
Asymmetrical large-joint oligoarthritis or monoarthritis Spinal (like AS)
Enthesitis
Dactylitis Other Features
Extra-articular: iritis, psoriaform rashes, oral ulcers, Psoriatic plaques
aortic regurg, IBD Nail changes
Pitting
Subungual hyperkeratosis
Ankylosing Spondylitis Onchyolysis
Chronic disease of unknown aetiology characterised by Enthesitis: Achilles tendonitis, plantar fasciitis
stiffening and inflammation of the spine and sacroiliac Dactylitis
joints.
X-Ray
Epidemiology Erosion pencil-in-cup deformity
Sex: M>F=6:1
Age: men present earlier late teens, early 20s Rx
Genetics: 95% are HLA-B27+ve NSAIDs
Sulfasalazine, methotrexate, ciclosporin
Presentation Anti-TNF
Gradual onset back pain
Radiates from SI joints to hips and buttocks
Worse @ night c morning stiffness Reactive Arthritis
Relieved by exercise. Sterile arthritis 1-4wks after urethritis or dysentery
Progressive loss of all spinal movements Urethritis: chlamydia, ureaplasma
Schobers test <5cm Dysentery: campy, salmonella, shigella, yersinia
Some develop thoracic kyphosis and neck
hyperextension = question mark posture Presentation
Enthesitis: Achilles tendonitis, plantar fasciitis Asymmetrical lower limb oligoarthritis: esp. knee
Costochondritis Iritis, conjunctivitis
Keratoderma blenorrhagica: plaques on soles/palms
Extra-articular manifestations Circinate balanitis: painless serpiginous penile ulceration
Osteoporosis: 60% Enthesitis
Acute iritis / anterior uveitis: 30% Mouth ulcers
Aortic valve incompetence: <3%
Apical pulmonary fibrosis Ix
ESR, CRP
Ix Stool culture if diarrhoea
Clinical Dx as radiological changes appear late Urine chlamydia PCR
Sacroliliitis: irregularities, sclerosis, erosions
Vertebra: corner erosions, squaring Mx
syndesmophytes (bony proliferations) NSAIDs and local steroids
Bamboo spine: calcification of ligaments, Relapse may need sulfasalazine or methotrexate
periosteal bone formation
FBC (anaemia), ESR, CRP, HLA-B27
DEXA scan and CXR
Enteropathic Arthritis
Mx Occurs in 15% of pts.
c UC or Crohns
Conservative
Exercise Presentation
Physio Asymmetrical large joint oligoarthritis mainly affecting
Medical the lower limbs.
NSAIDs: e.g. indomethacin Sacroiliitis may occur
Anti-TNF: if severe
Local steroid injections Rx
Bisphosphonates Treat the IBD
Surgical NSAIDs or articular steroids for arthritis
Hip replacement to pain and mobility Colectomy remission in UC

Autoimmune Connective Tissue Disease
Types Sjogrens Syndrome (= Keratoconjunctivitis Sicca)
SLE
Systemic Sclerosis Classification
1O Sjogrens Primary
Myositis F>>M=9:1
Mixed Connective Tissue Disease Onset 4th-5th decade
Relapsing Polychondritis Secondary
Behcets Disease RA
SLE
Systemic Sclerosis
Autoantibodies
Features
RF
tear production dry eyes
Sjogrens 100%
salivation xerostomia
Feltys 100%
Bilateral parotid swelling
RA 70%
Vaginal dryness dyspareunia
ANA Systemic
SLE >95% Polyarthritis
Raynauds
AIH 75%
Bibasal pulmonary fibrosis
Sjogrens 70%
Vasculitis
Myositis
dsDNA SLE
Histone Drug-induced lupus
Associations
Centromere CREST Syndrome
AI: thyroid disease, AIH, PBC
ENAs
SLE, Sjogrens, heart block Marginal zone MALT lymphoma
- Ro
- La SLE, Sjogrens
- Sm SLE Ix
- RNP SLE, MCTD Schirmer tear test
- Jo-1 Polymyositis, Dermatomyositis Abs: ANA Ro and La, RF
- Scl70 Diffuse Systemic Sclerosis Hypergammaglobulinaemia
- RNA pol 1/2/3 Diffuse Systemic Sclerosis Parotid biopsy
Relapsing Polychondritis Rx
Rare inflammatory disease of cartilage Artificial tears
Saliva replacement solutions
Presentation NSAIDs and hydroxychloroquine for arthralgia
Tenderness, inflammation and destruction of cartilage Immunosuppression for severe systemic disease
Ear floppy ears
Nose saddle-nose deformity
Larynx stridor Raynauds Phenomenon
Peripheral digital ischaemia precipitated by cold or
Associations emotion.
Aortic valve disease
Polyarthritis Classification
Vasculitis Idiopathic / 1O: Raynauds Disease
Secondary: Raynauds Syndrome
Rx Systemic sclerosis, SLE, RA, Sjogrens
Immunosuppression Thrombocytosis, PV
-blockers
Behcets Disease
Presentation
Systemic vasculitis of unknown cause
Digit pain + triphasic colour change: WBC
White, Blue, Crimson
Presentation
Digital ulceration and gangrene
Turks, Mediterraneans and Japanese
Recurrent oral and genital ulceration Rx
Eyes: ant/post uveitis Wear gloves
Skin lesions: EN CCBs: nifedipine
Vasculitis ACEi
Joints: non-erosive large joint oligoarthropathy IV prostacyclin
Neuro: CN palsies
GI: diarrhoea, colitis
MCTD / UCTD
Ix: skin pathergy test (needle prick papule formation) Combined features of SLE, PM, RA, SS
Rx: immunosuppression Ab: RNP
Systemic Sclerosis Polymyositis and Dermatomyositis
Striated muscle inflammation
Epidemiology
F>M=3:1 Principal Features
30-50yrs Progressive symmetrical proximal muscle weakness.
Wasting of shoulder and pelvic girdle
Limited Systemic Sclerosis: 70% Dysphagia, dysphonia, respiratory weakness
(includes CREST syndrome) Assoc. myalgia and arthralgia
Calcinosis Commoner in females
Raynauds Often a paraneoplastic phenomenon
Esophageal and gut dysmotility GOR Lung, pancreas, ovarian, bowel
Sclerodactyly
Telangiectasia Dermatomyositis = myositis + skin signs
Skin involvement limited to face, hands and feet Heliotrope rash on eyelids oedema
Beak nose Macular rash (shawl sign +ve: over back and shoulders)
Microstomia Nailfold erythema
Pulmonary HTN in 15% Gottrons papules: knuckles, elbows, knees
Mechanics hands: painful, rough skin cracking of finger
Diffuse Systemic Sclerosis: 30% tips
Diffuse skin involvement Retinopathy: haemorrhages and cotton wool spots
Organ fibrosis Subcutaneous calcifications
GI: GOR, aspiration, dysphagia, anal incontinence
Lung: fibrosis and PHT Extra-Muscular Features
Cardiac: arrhythmias and conduction defects Fever
Renal: acute hypertensive crisis (commonest Arthritis
cause of death) Bibasal pulmonary fibrosis
Raynauds phenomenon
Ix Myocardial involvement: myocarditis, arrhythmias
Bloods: FBC (anaemia), U+E (renal impairment)
Abs Ix
Centromere: limited Muscle enzymes: CK, AST, ALT, LDH
Scl70 / topoisomerase: diffuse Abs: Anti-Jo1 (assoc.
c extra-muscular features)
RNA pol 1,2,3: diffuse
EMG
Urine: stix, PCR
Muscle biopsy
Imaging
Screen for malignancy
CXR: cardiomegaly, bibasal fibrosis
Tumour markers
Hands: calcinosis
CXR
Ba swallow: impaired oesophageal motility
Mammogram
HiRes CT
Pelvic/abdo US
Echo
CT
ECG + Echo: evidence of pulmonary HTN
Differential
Mx
Inclusion body myositis
Conservative
Muscular dystrophy
Exercise and skin lubricants: contractures
Polymyalgia rheumatica
Hand warmers: Raynauds
Endocrine / metabolic myopathy
Medical
Immunosuppression Drugs: steroids, statins, colchicine, fibrates
Raynauds: CCBs, ACEi, IV prostacyclin
Renal: intensive BP control ACEi 1st line Mx
Oesophageal: PPIs, prokinetics (metoclopramide) Screen for malignancy
PHT: sildenafil, bosentan Immunosuppression
Steroids
Cytotoxics: azathioprine, methotrexate

Systemic Lupus Erythematosus
Definition Drug-Induced Lupus
Multisystemic autoimmune inflammatory disease in Causes: procainamide, phenytoin, hydralazine, isoniazid
which autoAbs to a variety of autoantigens result in the Anti-histone Abs in 100%
formation and deposition of immune complexes. Mostly skin and lung signs
Disease remits if drug stopped
Epidemiology
Prev: 0.2% Anti-Phospholipid Syndrome
Sex: F>>M=9:1
Age: child-bearing age Classification
Genetic: in Afro-Caribs and Asians Primary: 70%
Secondary to SLE: 30%
Features Pathology
Relapsing, remitting history Anti-phospholipid Abs: anti-cardiolipin and lupus
Constitutional symptoms: fatigue, wt. loss, fever, myalgia anticoagulant
A RASH POINts an MD Features

Arthritis CLOTs: venous (e.g. DVT) and arterial (e.g. stroke)
Non-erosive, involving peripheral joints Coagulation defect: APTT
Jaccouds: reducible deforming arthropathy Livido reticularis
st
Renal Obstetric complications: recurrent 1 trimester abortion
proteinuria and BP Thrombocyotpenia
ANA (+ve in 95%)
Serositis Rx
Pleuritis: pleuritic pain, dyspnoea, effusion Low-dose aspirin
Pericarditis: chest pain relieved by sitting forwards Warfarin if recurrent thromboses: INR 3.5
Haematological
AIHA
WCC Mx
Plats In specialist SLE and lupus nephritis clinics
Photosensitivity
Oral ulcers Severe Flares: Acute SLE
Immune phenomenon AIHA, nephritis, pericarditis or CNS disease
Anti-dsDNA High-dose prednisolone + IV cyclophosphamide
Anti-Sm
Anti-phospholipid Cutaneous Symptoms
Neurological Treat
c topical steroids and prevent
c sun cream
Seizures, psychosis
Malar Rash Maintenance
Facial erythema sparing the nasolabial folds For joint and skin symptoms
Discoid Rash NSAIDs and hydroxychloroquine low-dose steroids
Erythema pigmented hyperkeratotic papules
atrophic depressed lesions Lupus Nephritis
Mainly affects face and chest Proteinuria: ACEi
Aggressive GN: immunosuppression
Immunology Rx Complications
95% ANA+ve risk of osteoporosis and CV disease
dsDNA is very specific (sensitivity 60%)
30% ENA+ve: Ro, La, Sm, RNP
Anticardiolipin Abs false +ve syphilis serology Prognosis
80% survival @ 15yrs
Monitoring Disease Activity

Anti-dsDNA titres
Complement: C3, C4
ESR
Other Ix
Bloods: FBC, U+E, CRP, clotting (usually normal)
Urine: stix, PCR

Vasculitis
Classification Takayasus Arteritis = Pulseless Disease
Large Vessel Epidemiology
Giant Cell Arteritis Geo: Rare outside Japan
Takayasus Arteritis Sex: F>M
Age: 20-40yrs
Medium Vessel
Polyarteritis Nodosa Features
Kawasaki Disease Constitutional symptoms: fever, fatigue, wt. loss
Weak pulses in upper extremities
Small Vessel Visual disturbance
pANCA HTN
Churg-Straus
Microscopic Polyangiitis
cANCA: Wegeners Granulomatosis Polyarteritis Nodosa
ANCA ve
Henoch-Schonlein Purpura Epidemiology
Goodpastures Disease
Prev: rare in UK
Cryoglobulinaemia
Sex: M>F=2:1
Cutaneous Leukocytoclastic Vasculitis
Age: young adults
Giant Cell Arteritis / Temporal Arteritis Features
Common in elderly (rare <55) Assoc.
c Hep B
Assoc.
c PMR in 50%
Constitutional symptoms
Rash
Features
Renal HTN
Systemic signs: fever, malaise, fatigue
GIT melaena and abdo pain
Headache
Temporal artery and scalp tenderness Rx
Jaw claudication Pred + cyclophosphamide
Amaurosis fugax
Prominent temporal arteries pulsation
Mx and Ix Kawasakis Disease

If suspect GCA: Do ESR and start pred 40-60mg/d PO Childhood PAN variant
ESR and CRP
Features
ALP
5-day fever
Hb (normo normo), Plats
Bilat non-purulent conjunctivitis
Temporal artery biopsy w/i 3d: but skip lesion occur
Oral mucositis
Continuing Rx Cervical lymphadenopathy
Taper steroids gradually, guided by symptoms and ESR Polymorphic rash (esp. trunk)
PPI and alendronate cover (~2yr course usually) Extremity changes (erythema + desquamation)
Coronary artery aneurysms
PMR
Rx
Presentation IVIg + aspirin
>50yrs old
Severe pain and stiffness in shoulders, neck and hips
Sudden / subacute onset
Symmetrical
Worse in the morning: stops pt. getting out of bed
No weakness (cf. myopathy or myositis)
mild polyarthritis, tenosynovitis and carpal tunnel syn.
Systemic signs: fatigue, fever, wt. loss
15% develop GCA
Ix
ESR and CRP (+ plasma viscosity)
ALP
Normal CK
Rx
Pred 15mg/d PO: taper according to symptoms and ESR
PPI and alendronate cover (~2yr course usually)
ANCA Positive Vasculitidies ANCA Negative Vasculitidies
Wegeners Granulomatosis HSP (Childhood IgA nephropathy variant)
Necrotizing granulomatous inflammation and small vessel Children 3-8yrs
vasculitis
c a predilection for URT, LRT and Kidneys Post-URTI
Palpable purpura on buttocks
Features Colicky abdo pain
URT Arthralgia
Chronic sinusitis Haematuria
Epistaxis
Saddle-nose deformity
Goodpastures
LRT
Anti-GBM Abs
Cough
RPGN
Haemoptysis
Haemoptysis
Pleuritis
CXR: Bilat lower zone infiltrates (haemorrhage)
Renal
Rx
RPGN
Immunosuppresion + plasmapheresis
Haematuria and proteinuria
Other
Palpable purpura Cryoglobulinaemia
Ocular: conjunctivitis, keratitis, uveitis
Simple
Ix Monoclonal IgM
cANCA 2O to myeloma / CLL / Waldenstroms
Dipstick: haematuria and proteinuria Hyperviscosity
CXR: bilat nodular and cavity infiltrates Visual disturbance
Bleeding from mucus mems
Thrombosis
Headache, seizures
Churg-Strauss
Late-onset asthma
Mixed (80%)
Eosinophilia
Polyclonal IgM
Granulomatous small-vessel vasculitis O
2 to SLE, Sjog, HCV, Mycoplasma
RPGN
Immune complex disease
Palpable purpura
GN
GIT bleeding
Palpable purpura
pANCA
Arthralgia
May be ssoc.
c montelukast Peripheral neuropathy
Microscopic Polyangiitis Cutaneous Leukocytoclastic Vasculitis

RPGN Palpable purpuric rash
Haemoptysis arthralgia GN
Palpable purpura Causes
pANCA HCV
Drugs: sulphonamides, penicillin

Fibromyalgia
Epidemiology
10% of new rheum referrals
Prev: 0.5-4%
Sex: F>>M=10:1
Risk Factors
Neurosis: depression, anxiety, stress
Dissatisfaction at work
Overprotective family or lack of support
Middle age
Low income
Divorced
Low educational status
Associations
Chronic fatigue syndrome
Irritable bowel syndrome
Chronic headache syndromes
Features
Chronic, widespread musculoskeletal pain and
tenderness
Morning stiffness
Fatigue
Poor concentration
Sleep disturbance
Low mood
Ix
All normal
Rule out organic cause: FBC, ESR, CRP, CK, TFTs, Ca
Mx
Educate pt.
CBT
Graded exercise programs
Amitriptyline or pregabalin
Venlafaxine

Clinical Chemistry
Contents
Major Disease Patterns ............................................................................................................................................................. 212
Hyponatraemia .......................................................................................................................................................................... 213
Hypernatraemia ......................................................................................................................................................................... 213
Hypokalaemia ............................................................................................................................................................................ 214
Hyperkalaemia........................................................................................................................................................................... 214
Ca and PO4 Physiology ............................................................................................................................................................. 215
Hypocalcaemia .......................................................................................................................................................................... 215
Hypercalcaemia ......................................................................................................................................................................... 216
Osteoporosis ............................................................................................................................................................................. 216
Osteomalacia............................................................................................................................................................................. 217
Pagets Disease / Osteitis Deformans ....................................................................................................................................... 217
Metabolic Bone Disease Summary ........................................................................................................................................... 218
Hyperlipidaemia ......................................................................................................................................................................... 219
Porphyrias ................................................................................................................................................................................. 220
Acute Intermittent Porphyria ...................................................................................................................................................... 220
Rare Inherited Metabolic Disorder............................................................................................................................................. 221

Major Disease Patterns
Disease Biochemistry
Dehydration U, Cr
albumin
HCT
Low GFR U, Cr, H, K, urate
PO4, Ca
Tubular Dysfunction Normal U and Cr
K, urate, PO4, HCO3
Thiazide and Loop Diuretics Na, K, HCO3, U
Hepatocellular Disease EtOH: AST:ALT>2, GGT
Viral: AST:ALT<2
bilirubin, ALP, albumin, PT (APTT if end-stage)
Cholestasis ALP, GGT, Bilirubin, AST
Excess EtOH intake GGT, MCV, evidence of hepatocellular disease
Addisons K, Na
Cushings May show: K, Na, HCO3
Conns K, Na, HCO3
DM glucose
DI Na, serum osmolality, urine osmolality
SIADH Na, serum osmolality, urine osmolality (>500), urine Na

Hyponatraemia Hypernatraemia
<135: n/v, anorexia, malaise Thirst
<130: headache, confusion, irritability Lethargy
<125: seizures, non-cardiogenic pulmonary oedema Weakness
<115: coma and death Irritability
Confusion, fits, coma
Causes Signs of dehydration
Hypovolaemic Causes
U Na >20mM (= renal loss) Usually caused by dehydration ( intake or loss)
Diuretics
Addisons Hypovolaemic
Osmolar diueresis (e.g. glucose) GI loss: diarrhoea, vomiting
Renal failure (diuretic phase) Renal loss: diuretics, osmotic diuresis (e.g. DM)
U Na >20mM (= extra-renal loss) Skin: sweating, burns
Diarrhoea
Vomiting Euvolaemic
Fistula fluid intake
SBO DI
Burns Fever
Hypervolaemic Hypervolaemic
Cadiac failure Hyperaldosteronism (BP, K, alkalosis)
Nephrotic syndrome Hypertonic saline
Cirrhosis
Renal failure
Mx
Give water PO if possible
Euvolaemic
Otherwise, 5% dextrose IV slowly
U osmolality >500
SIADH Use 0.9% NS if hypovolaemic or Na >170mM
Causes less marked fluid shifts
U osmolality <500
Water overload Aim for Na 12mM/d
Severe hypothyroidism Too fast cerebral oedema
Glucocorticoid insufficiency
Free Water Deficit
TBW (L) = coeff x wt.
Mx Coeff = men:0.6, women:0.5
Correct the underlying cause
Def (L) = TBW x (1-[140/Na])
Replace Na and water at the same rate they were lost
Too fast central pontine myelinolysis
Chronic: 10mM/d Diabetes Insipidus
Acute: 1mM/hr Polyuria
Asymptomatic chronic hyponatraemia Polydipsia
Fluid restrict Dehydration
Symptomatic / acute hyponatraemia / dehydrated
Cautious rehydration with 0.9% NS Causes
If hypervolaemic consider frusemide Nephrogenic
Emergency: seizures, coma Inherited
Consider hypertonic saline (e.g. 1.8%) Ca
Drugs: Li, demeclocycline
Post-obstructive uropathy
SIADH Cranial
Concentrated urine: Na >20mM, osmolality >500 Idiopathic
Hyponatraemia or plasma osmolality <275 Congenital: DIDMOAD
Absence of hypovolaemia, oedema or diuretics Tumor
Trauma
Causes Vascular: haemorrhage
Resp: SCLC, pneumonia, TB Infection: meningoencephalitis
CNS: meningoencephalitis, head injury, SAH
Endo: hypothyroidism Ix
Drugs: cyclophosphamide, SSRIs, CBZ Na
Dilute urine
Rx Dx: Water deprivation test
Rx cause and fluid restrict
Vasopressin receptor antagonists Rx
Demeclocycline Treat cause
Vaptans Desmopressin if cranial
Hypokalaemia Hyperkalaemia
Symptoms Symptoms
Muscle weakness Fast, irregular pulse
Hypotonia Palpitations
Hyporeflexia Chest pain
Cramps Weakness
Tetany
Palpitations
Arrhythmias ECG
Tall tented T waves
NB. K exacerbates digoxin toxicity Flattened P waves
PR interval
Widened QRS
ECG Sine-wave pattern VF
Result from delayed ventricular repolarisation
Flattened / inverted T waves
Prominent U waves (after T waves) Causes
ST depression
Long PR interval Artefact
Long QT interval Haemolysis
K2EDTA contamination from FBC bottle
Leucocytosis, thrombocytosis
Causes Drip arm
Internal Distribution Internal Distribution

Alkalosis Acidosis
insulin insulin
-agonists Cell death / tissue trauma / burns
Digoxin poisoning
Excretion Suxamethonium
GI: vomiting, diarrhoea, rectal villous adenoma
Renal: RTA (esp. type 2), Bartter syn. Excretion
Drugs: diuretics, steroids Oliguric renal failure
Endo: Conns syn., Cushings syn. Addisons
+
Drugs: ACEi, NSAIDs, K -sparing diuretics
Input
Inappropriate IV fluid management Input
Excessive K therapy
Massive transfusion
Mx
1mM K = ~200-300mmol total deficit
Dont give K if oliguric Mx
Never give STAT fast bolus
Non-urgent
Mild: K >2.5 Treat cause: review meds
Oral K supplements Polystyrene sulphonate resin (Calcium Resonium)
80mmol/d Binds K in the GIT and K over days
Severe: K <2.5 and/or dangerous symptoms Emergency: evidence of myocardial instability or K >6.5
IV KCl cautiously 10ml 10% calcium gluconate
10mmol/h (20mmol/h max) 100ml 20% glucose + 10u insulin (Actrapid)
Best to give centrally (burning sensation peripherally) Salbutamol 5mg nebulizer
Max central conc: 60mM Haemofiltration (usually needed if anuric)
Max peripheral conc: 40mM Calcium resonium 15g PO or 30g PR
Mg Replacement
Pts. are often Mg deplete too
Until Mg is replaced the K will not return to normal
levels despite K replacement
Give empiric Mg replacement

Ca and PO4 Physiology Hypocalcaemia
PTH Presentation: SPASMODIC
Overall: Ca and PO4 Spasms (carpopedal = Trousseaus sign)
ionised Ca PTH release Perioral paraesthesia
Anxious, irritable
Renal Seizures
Ca reabsorption Muscle tone : colic, wheeze, dysphagia
PO4 reabsorption Orientation impaired (confusion)
1-hydroxylation of 25-OH-Vit D3 in kidney Dermatitis: atopic, exfoliative
HCO3 excretion (may mild met acidosis) Impetigo herpetiformis (Ca + pustules in cyesis)
Chovsteks, Cardiomyopathy ( QTc TdP)
Bone Ca threshold for action potential
osteoclast activity Ca, PO4
Causes
Commonest cause is CRF
Vitamin D and Calcitriol
Hepatic 25 hydroxylation 25-OH-Vit D3 (Calcidiol) With PO4
Renal 1-hydroxylation in kidney 1,25(OH)2 Vit D3 CKD
(Calcitriol) Hypoparathyroidism / pseudoyhpoparathyroidism
by PTH, Ca or PO4 Mg
Acute rhabdomyolysis (muscle Ca deposition)
GIT
Ca and PO4 absorption With normal or PO4
Inhibition of PTH release Osteomalacia
Active pancreatitis
Renal Respiratory alkalosis
Ca and PO4 reabsorption
Rx
Magnesium Mild
Mg prevents PTH release Ca 5mmol QDS PO
May Ca Daily Ca levels
CKD
Plasma Binding Alfacalcidol (1-OH-Vit D3)
2.2-2.6mM
50% albumin bound ( Alb Ca) Severe
Labs measure total Ca 10ml 10% Ca gluconate IV (2.25mmol) over 30min
cCa: Ca by 0.1mM for every 4g/L albumin Repeat as necessary
below 40g/L
Alkalosis albumin protonation Ca binding
[Ca]
NB. Prolonged tourniquet application albumin Ca

Take uncuffed specimen if concerned

Hypercalcaemia Osteoporosis
Presentation Definition
Stones bone mass
Renal stones 1O: age-related
Polyuria and polydipsia (nephrogenic DI) 2O: drugs or other condition
Nephrocalcinosis
Bones Risk Factors: SHATTERED
Bone pain Steroids
Pathological #s Hyperthyroidism, HPT, HIV
Moans: depression, confusion Alcohol and Cigarettes
Groans Thin (BMI <22)
Abdo pain Testosterone Low
n/v and constipation
Early Menopause
Pancreatitis
Renal / liver failure
PUD (gastrin secretion)
Erosive / inflam bone disease (e.g. RA, myeloma)
Other:
2+
BP (check Ca in all with HTN) Dietary Ca low / malabsorption
QT interval
Presentation
Vertebral crush #s
# NOF and other long bone #s
Causes
Most commonly malignancy or 1O HPT
Ix: Bone profile, FBC, U+E
With PO4
ALP (e.g. bone turnover) DEXA Scan
Bone mets Indications
thyroid, breast, lung, kidney, prostate, colon Low-trauma #
Sarcoidosis Women 65yrs c one or more risk factors
Thyrotoxicosis Before giving long-term steroids (>3mo)
Lithium Parathyroid disorders, myeloma, HIV
Normal ALP Interpretation
Myeloma T: no. of SDs away from youthful average
Hypervitaminosis D Z: no. of SDs away from matched average
Sarcoidosis T > -1 = normal
Milk alkali syn. T -1 - -2.5 = osteopenia
T <-2.5 = osteoporosis
With normal or PO4
1O or 3O HPT Rx
Familial benign hypercalciuria Decision to instigate pharmacological Rx is based
AD upon age, RFs, and BMD.
Ca-sensing receptor set-point FRAX can estimate 10yr # risk
Paraneoplastic: PTHrP (but PTH)
Conservative
Stop smoking, EtOH
Ix Wt. bearing or balancing exercise (e.g. Tai Chi)
PTH = 1O or 3O HPT Ca and vit-D rich diet
PTH: most likely Ca Home-based fall-prevention program c visual
FBC, protein electrophoresis, CXR, bone scan assessment.
Primary and secondary prevention of #s

st
Bisphosphonates: alendronate is 1 line
Mx Ca and Vit D supplements: e.g Calcium D3 Forte
Dx and Rx underlying cause
Strontium ranelate: bisphosphonate alternative
Rehydrate
Alternative for 2O prevention of osteoporotic #s
1L 0.9% NS / 4h
Raloxifene: SERM, breast Ca risk cf. HRT
Monitor pts. hydration state
Teriparetide: PTH analogue new bone formation
Denosumab: anti-RANKL osteoclast activation
Frusemide
Only start once pt. is volume replete
Bisphosphonate SEs
Calciuric + makes room for more fluids
GI upset
Oesophageal ulceration / erosion
Bisphosphonates
Take
c plenty of water on an empty stomach
Ca bisphosphonate cant be resorbed by osteoclasts
and refrain from lying and dont eat for 30min.
Only used in hypercalcaemia of malignancy
Diffuse musculoskeletal pain
Can obscure Dx as Ca, PO4 and PTH
Osteonecrosis of the jaw
E.g. Pamidronate, Zoledronate (IV)
Osteomalacia Pagets Disease / Osteitis Deformans
Definition Pathophysiology
bone mineral content Affects 3% over 55yrs
Excess uncalcified osteoid and cartilage bone turnover bone remodelling, enlargement,
weakness and deformity.
Presentation bone mass but disordered and weak
Commoner in temperate climes and Anglo-Saxons
Rickets: children
Knock-kneed / bow-legged 3 Phases
Bone pain Osteolytic
Craniotabes Mixed Osteolytic-osteoblastic
Osteochondral swelling: rachitic rosary Quiescent osteosclerotic stage
Harrisons sulcus
Presentation
Osteomalacia: adults (after epiphyseal fusion) Asymptomatic in 70%
Bone pain and tenderness Predominantly affects the axial skeleton
#s: esp. NOF Pelvis, lumbar spine, skull, femur and tibia
Proximal myopathy due to PO4 Polyostotic in 85%
Bone pain
Causes Pathological #
Vitamin D deficiency: malabsorption, poor diet, sunlight Deformity
Renal osteodystrophy: 1 hydroxylation Sabre tibia
Drugs: AEDs hepatic vit D metabolism Head enlargement
Vit D resistance: inherited conditions
Type 1: renal hydroxylation Complications
Type 2: end-organ resistance Nerve compression: deafness, radiculopathy
Hepatic disease: malabsorption and 25 hydroxylation High output CCF
Malignancy: oncogenic hypophosphataemia Osteosarcoma (<1% after 10yrs)
fibroblast growth factor-23 hyperphosphaturia Sudden onset or worsening of bone pain
Ix Ix
Ca, PO4, ALP, PTH, 25-OH Vit D3 (unless resistance) ALP, (Ca and PO4 normal)
X-ray Bone scan: hot spots
Loss of cortical bone X-ray
Loosers zones: pseudofractures Bone enlargement
Cupped metaphyses in Rickets Sclerosis
Patchy cortical thickening
Rx Deformity
Wedge-shaped lytic lesions
Dietary: Calcium D3 Forte
Osteoporosis circumscripta
Malabsorption or hepatic disease
Well-defined lytic skull lesions
Vit D2 (ergocalciferol) PO
Parenteral calcitriol
Renal disease or vit D resistance Mx
1-OH-Vit D3 (alfacalcidol) Analgesia
1,25-(OH)2 Vit D3 (calcitriol) Alendronate: pain and/or deformity
Monitor plasma Ca

Metabolic Bone Disease Summary
Disease Aetiology Characteristics Symptoms Risk Factors Biochemistry
Ca PO4 ALP PTH
Osteoporosis 1o: age, post-menopausal Normal bone quality, bone density: Back pain SHATTERED N N N N
2o: drugs, systemic disease T -1 - -2.5 = osteopenia Fractures
T <-2.5 = osteoporosis
Osteomalacia Vit D or PO4 deficiency Defective bone mineralisation Bone pain Vegan
- osteoid #s Breast milk
- widened osteoid seams Proximal weakness Malabsorption
Bone deformity sun
Ca SPASMODIC CLD
Rickets Loosers zones on X-ray Craniotabes CRD /N
- pseudofractures Frontal bossing
Rachitic rosary
Bowed legs
Cupped metaphysis @ wrist
1o HPT 80% parathyroid adenomas Osteitis fibrosa cystica Stones, bones, moans, groans /N
20% gland hyperplasia - Subperiosteal erosions
<0.5% parathyroid Ca - Acral osteolysis
2o HPT Chronic renal failure - Cysts
Vit D deficiency - Brown tumours (fibrous, vascular)
Malabsorption - Pepperpot skull
3o HPT Parathyroid hyperplasia due to Stones, bones, moans, groans Post-renal Tx /N
prolonged 2o HPT
Hypo-PTH Surgical Spasmodic N /N
Autoimmune
Congen Di George
Pagets Unknown Disorder of bone turnover bone Bone pain N N N
mass but bone is disordered + weak Sabre tibia
- disorganised mosaic pattern of Chalkstick #
lamellar bone Nerve compression
- sclerosis + cortical thickening - deafness
Heart failure
Axial skeleton, esp. skull, pelvis
risk of osteosarcoma
Wedge-shaped lytic lesions

Osteoporosis circumscripta
Renal PO4 retention + vit D Ca bone resorption osteitis fibrosa Bone pain /N
osteodystrophy PTH Osteomalacia #s
Osteosclerosis: rugger jersey spine Uraemia
Met acidosis of RF release of Osteoporosis
hydroxyapataite

Hyperlipidaemia
Biology Presentation
Chylomicrons CVD
Mainly TG Xanthomata
Carry dietary TG tissues Eruptive: itchy nodules in crops (TG)
VLDL Tuberous: plaques on elbows, knees
Mainly TG Planar: ornage streaks in palmer creases
Take endogenous TG from liver tissue Remnant hyperlipidaemia
LDL Xanthelasma: eyelids
Mainly cholesterol Arcus: cornea
Carry cholesterol from liver to tissues Pancreatitis (TG)
HDL
Mainly phospholipid
Take cholesterol from tissues liver for excretion
Apolipoproteins
Ix
Contained in lipoproteins and control transport and Plasma cholesterol
uptake. Plasma HDL
ApoB contained in LDL and binds to cell receptors Fasting TGs
uptake TC:HDL ratio is best predictor of CV risk
Classification Mx
O
Common 1 hyperlipidaemia
70% Aims
Dietary and genetic factors TC <4
LDL only TC:HDL ratio <4.5
Familial primary hyperlipidaemia
Multiple phenotypes Lifestyle
risk of CVD Lose wt.
2O hyperlipidaemia saturated fat, fibre, fruit and veg
LDL exercise
Nephrotic syn.
Cholestasis: lipoprotein x Treatment Priorities
Hypothyroidism Known CVD
Cushings Those
c DM
Drugs: thiazides, steroids Those
c 10yr CVD risk >20%
Mixed: LDL and TG Irrespective of baseline lipids
T2DM
st
EtOH 1 -line: Statins
CRF E.g. simvastatin 40mg PO nocte
HMG-CoA reductase inhibitors cholesterol synth.
Familial Primary Hyperlipidaemias 2nd-line:

Fibrates: PPAR antagonists, TGs
1O Hypercholesterolaemia Ezetimibe: inhibits cholesterol absorption
Commonest Niacin / nicotinic acid: HDL, LDL
ApoB (LDL receptor) defect LDL-C
Combined Hyperlipidaemia
2nd commonest
LDL-C + TG
Lipoprotein Lipase Deficiency

chylomicrons
Hypertriglyceridaemia
Remnant Particle Disease

Porphyrias
Pathogenesis Porphyria Cutanea Tarda
Deficiencies of enzymes in haem biosynthesis Commonest porphyria
overproduction of toxic haem precursors Cutaneous manifestations only
Porphyrins: induce photosensitivity Uropophyrinogen decarboxylase deficiency
Porphyrin precursors: neurotoxic
Genetic or acquired Presentation
EtOH, lead and Fe abnormal porphyrin Photosensitivity: blistering skin lesions
metabolism Facial hyperpigmentation and hypertrichosis
Precipitants
Acute Intermittent Porphyria Sunlight
The Madness of King George
EtOH
2nd commonest porphyria
Ix
Pathophysiology
urine and se porphyrins
AD
c partial penetrance
se ferritin
Porphyrobilinogen deaminase deficiency
F>M = 2:1 Rx
Presents @ 20-40yrs Avoid sun
Phlebotomy / iron chelators
Presentation Chloroquine
GI: Abdo pain, n/v, constipation
CV: HR, BP (sympathetic overactivity)
Neuropsych: peripheral motor neuropathy, seizures,
psychosis
Other: Red urine, fever, WCC
NB. Can mimic surgical abdomen (anaesthesia = disaster)
Precipitants
P450 inducers: AEDs, EtOH, OCP/HRT
Infection / stress
Fasting
Pre-menstrual
Ix
urine PBG and ALA
Rx
Supportive
Analgesia: opiate (avoid oxycodone)
IV fluids
Carbohydrate
Rx HR and BP c -B
Specific
IV haematin

Rare Inherited Metabolic Disorders
Homocystinuria
Auto recessive
Cystathione -synthetase deficiency
Accumulation of homocystine
Presentation
Marfanoid habitus
Downward lens dislocation
Mental retardation
Heart rarely affected
Recurrent thrombosis
Rx
Some response to high-dose pyridoxine
Gauchers Disease
Commonest lysosomal storage disease
Autosomal recessive glucocerebrosidase deficiency
accumulation of glucosylceramide in the
lysosomes of the reticuloendothelial system.
Liver
BM
Spleen
High incidence in Ashkenazi Jews (1/450)
Presentation
3 clinical types: type 1 is commonest
Presents in adulthood
Gross HSM
Brown skin pigmentation: forehead, hands
Pancytopenia
Pathological fractures
Mx
Most have normal life expectancy in type 1
Can give recombinant enzyme replacement

Oncology
Contents
Genetic Oncology ...................................................................................................................................................................... 223
Epidemiology ............................................................................................................................................................................. 223
Oncological Emergencies .......................................................................................................................................................... 224
Cancer Therapy ......................................................................................................................................................................... 225
Tumour Markers ........................................................................................................................................................................ 226

Genetic Oncology Epidemiology
Cancer affects 30% of the population
Familial Breast and Ovarian Ca 20% of people die from cancer
~10% of breast Ca is familial
~5% is caused by BRCA1 or BRCA2 mutations
Both TSGs Commonest Incidence
BRCA1: Breast Ca 80%, Ovarian Ca 40% 1. Skin cancers
BRCA2: Breast Ca 80%, male breast Ca 2. Breast / Prostate
May opt for prophylactic mastectomy and oophrectomy. 3. Lung
4. CRC
Familial Prostate Ca
~5% of those c prostate Ca have +ve fam Hx Commonest Mortality
Multifactorial inheritance Lung
BRCA1/2 moderately risk Breast / Prostate
CRC
Familial CRC
~20% of those c CRC have +ve fam Hx
Relative risk of CRC for individual
c FH related to
Closeness of relative
Age of relative when Dx.
Familial Adenomatous Polyposis

Mutation in APC gene on Chr 5
TSG
Promotes -catenin degredation
-catenin is an oncogene which cell
proliferation
Cells then acquire another mutation to become Ca
p53
kRAS
AD transmission
~100% risk of CRC by 50yrs
HNPCC
Familial clustering of cancers
Lynch 1: CRC
Lynch 2: CRC + other Ca
Ovarian
Endometrial
Pancreas
Small Bowel
Renal pelvis
Mutations in DNA mismatch repair genes
AD transmission (variable penetrance)
Often Right-sided CRC
Present @ young age: <50yrs
Peutz-Jehgers
AD transmission
Multiple GI hamartomatous polyps
Mucocutaneous hyperpigmentation
Lips
Palms
10-20% lifetime risk of CRC
Also risk of other Ca
Pancreas
Lung
Breast
Ovaries and uterus
Testes

Oncological Emergencies
Febrile Neutropenia Hypercalcaemia
PMN <1x109/L Affects 10-20% of those
c Ca
Isolation + barrier nursing Affects 40% of those
c myeloma
Meticulous antisepsis
Broad-spectrum Abx, anti-fungals, anti-virals Causes
Prophylaxis: co-trimoxazole Lytic bone metastases
Production of PTHrP
Spinal Cord Compression Symptoms

Confusion
Presentation Renal stones
Back pain, radicular pain Polyuria and polydipsia dehydration
Motor, reflex and sensory level Abdominal pain, constipation
Bladder and bowel dysfunction Depression
Lethargy
Causes Anorexia
Usually extradural metastasis
Crush fracture Ix
Ca (often >3mM)
O
Ix PTH (key to exclude 1 HPT)
Urgent MRI spine CXR
Isotope bone scan
Mx
Dexamethasone Rx
Discuss
c neurosurgeon and oncologist Aggressive hydration
Consider radiotherapy or surgery 0.9% NS (e.g. 1L/4h)
Monitor volume status
Frusemide when full to make room for more fluid
O
If 1 HPT excluded, give maintenance therapy
c
SVCO
c Airway Compromise
bisphosphonate: zoledronate is good
SVCO not an emergency unless theres tracheal
compression
c airway compromise.
Causes Raised ICP

Usually lung Ca
Thymus malignancy Presentation
LNs Headache: worse AM and bending over
SVC thrombosis: central lines, nephrotic syndrome n/v
Fibrotic bands: lung fibrosis after chemo Focal neuro and fits
Papilloedema
Presentation
Headache Ix
Dyspnoea and orthopneoa CT/MRI
Plethora + thread veins in SVC distribution
Rx
Swollen face and arms
Dexamethasone
Engorged neck veins
Radio- / chemo-therapy
Pembertons Sign
Lifting arms above head for >1min facial plethora,
JVP and inspiratory stridor Tumour Lysis Syndrome
Due to narrowing of the thoracic inlet Massive cell destruction
High count leukaemia or bulky lymphoma
Ix K, urate, PO4, Ca
Sputum cytology renal failure
CXR Prevention
CT fluid intake + allopurinol 24h before chemo
Venography Rasburicase is an option
Mx
Dexamethasone
Consider balloon venoplasty + SVC stenting
Radical or palliative chemo / radio

Cancer Therapy
Cancer must be managed in an MDT Radiotherapy
Chemotherapy Mechanism
Neoadjuvant Ionising radiation free radicals which damage DNA
Shrink tumour to need for major surgery Normal cells better at repairing damage cf. Ca cells.
Control early micrometastases Radiation dose: gray (Gy)
Primary Therapy Given in daily fractions
E.g. sole Rx in haematological Ca India ink tattoo for reproducible targeting
Adjuvant
chance of relapse: e.g. breast and GI Ca Radical Rx
Palliative Curative intent
Provide relief from symptoms 40-70Gy
Prolong survival 15-30 daily fractions
Important Cytotoxic Classes Palliation

Symptom relief
Alkylating agents Bone pain, haemoptysis, cough, dyspnoea,
Cyclophosphamide, chlorambucil, busulfan bleeding.
8-30Gy
Antimetabolites: methotrexate, 5-FU 1-10 fractions
Vinca alkaloids: vincristine, vinblastine Early Reactions

Tiredness
Cytotoxic Abx: doxorubicin, bleomycin, actinomycin D Skin reactions: erythema ulceration
Mucositis
Taxanes: paclitaxel n/v: occur c stomach, liver or brain Rx
Diarrhoea: pelvic or abdo Rx
Immune Modulators: thalidomide, lenalidomide
Cystitis
MAbs BM suppression
Trastuzumab (anti-Her2): breast Ca
Late Reactions (months or yrs)
Bevacizumab (anti-VEGF): RCC, CRC, lung
Brachial plexopathy
Cetuximab (anti-EGFR): CRC
Follows axillary radiotherapy
Rituximab (anti-CD20): NHL
Numb, weak, painful arm
Lymphoedema
Tyrosine Kinase Inhibitors
Pneumonitis
Erlotinib: lung Ca
Dry cough dyspnoea
Imatinib: CML
Rx: prednisolone
Xerostomia
Endocrine Modulators: tamoxifen, anastrazole
Benign strictures
Fistulae
Common Side Effects
fertility
n/v: prophylactic granisetron + dexamethasone
Panhypopituitarism
Alopecia
Neutropenia: 10-14d after chemo
Extravasation of chemo agent
Pain, burning, bruising @ infusion site
Surgery
Stop infusion, give steroids, apply cold pack Diagnostics: tissue biopsy or complete removal
Liaise early c plastics Excision: GI, soft-tissue sarcomas, gynae
Often with neo-/adjunctive chemo or radiotherapy
Palliation: e.g. bypass procedures, stenting
Specific Problems
Drug Problems
Cyclophosphamide Haemorrhagic cystitis: give mesna
Analgesia
Hair loss Oral where possible
BM suppression Fixed interval to give continuous relief
Doxorubicin Cardiomyopathy Stepwise approach
Bleomycin Pulmonary fibrosis
Vincristine Peripheral neuropathy (dont give IT)
Carboplatin Peripheral neuropathy
n/v
Nephrotoxic
Paclitaxel Hypersenstivity
5-FU Mucositis

Tumour Markers
Marker Malignant Non-malignant
AFP HCC Hepatitis
Teratoma Cirrhosis
Pregnancy
CA 125 Ovary Cirrhosis
Uterus Pregnancy
Breast
CA 15-3 Breast Benign breast disease
CA 19-9 Pancreas Cholestasis
Cholangiocarcinoma Pancreatitis
CRC
CA 27-29 Breast
Neuron-specific SCLC
enolase
CEA CRC Pancreatitis
Cirrhosis
HCG Germ cell tumour Pregnancy
PSA Prostate BPH
Mono Ig Multiple myeloma
S-100 Melanoma Sarcoma
PLAP Seminoma
Acid phosphatases Prostate Ca
Thyroglobulin Thyroid Ca

Immunology
Contents
Phagocyte Deficiencies ............................................................................................................................................................. 228
T Cell Deficiency........................................................................................................................................................................ 228
B Cell Deficiency ....................................................................................................................................................................... 229
Complement Dysfunction .......................................................................................................................................................... 230
Infections Associated With Immune Deficiencies ...................................................................................................................... 231

Phagocyte Deficiencies
Condition Mechanisms Presentation PMN Adhesion Mol NBT/DHR Pus
Reticular dysgenesis HSC defect
Deficiency of PMN, lymphos, monos
Type of SCID
Kostmanns Syndrome Congenital neutropenia Rx: G-CSF or BMT Absent Normal Absent No
Auto Recessive
Cyclic neutropenia Episodic neutropenia every 4-6 wks Rx: G-CSF
Auto Dominant
Mutation in ELA2 gene
LAD CD18 (2-integrin) deficiency Delayed umbilical cord separation Absent Normal No
Neonatal bacterial infections
CGD NADPH oxidase deficiency Recurrent pneumonias and abscesses Normal Normal Abnormal Yes
X-linked recessive Granulomas
Can resist catalase negative bacteria Lymphadenopathy
HSM
Rx: gamma-IFN therapy
Cytokine Failure gIFN / gIFN-R and Susceptible to mycobacteria and salmonella
IL-12 / IL-12-R deficiency BCG infection after vaccination
No granulomas
T Cell Deficiencies
Condition Mechanisms Presentation CD4 CD8 B Cell IgM IgG IgA
HSC defect
Reticular dysgenesis
Deficiency of PMN, lymphos, monos
Type of SCID
X-linked: (common) IL2R gamma chain mutation Unwell by 3mo
SCID
- T-/B+ Infections N/ N/
FTT
ADA deficiency: auto recessive Persistent diarrhoea
- T-/B- Unusual skin disease
FH of early infant death
Defect of 3rd/4th pharyngeal arches Immune function improves with age.
Di George
Thymic aplasia Rx: Thymus transplant N N
CATCH-22
Absent MHC-II Unwell by 3mo
BLS-II
FTT N N N
Assoc. with sclerosing cholangitis
Cytokine Failure gIFN / gIFN-R and Susceptible to mycobacteria and salmonella
IL-12 / IL-12-R deficiency BCG infection after vaccination
No granulomas

B Cell Deficiencies
Condition Mechanisms Clinical CD4 CD8 B Cell IgM IgG IgA
X-linked: (common) IL2R gamma chain mutation Unwell by 3mo
SCID
- T-/B+ Infections N/ N/
FTT
ADA deficiency: auto recessive Persistent diarrhoea
- T-/B- Unusual skin disease
X-linked No Ig after ~3mo
Brutons
B-cell tyrosine kinase deficiency Recurrent childhood infections N N
Pre-B cells cannot mature - bacterial
- enterovirus
X-linked Boys present in first few yrs
Hyper IgM
CD40L (CD154) mutation (T cells) Recurrent bacterial infections N N N
No germinal centre development in LN/spleen FTT
Failure of isotype switching PCP, autoimmune disease, Ca
Assoc. with coeliac disease
IgA deficiency
Recurrent GIT and RT infections N N N N N
Not severe
Recurrent bacterial infections
Common variable ID
- bronchiectasis N N N N
- sinusitis
Autoimmune disease
Granulomatous disease
WASP gene mutation Immunodeficiency
Wiskott-Aldrich
X-linked Thrombocytopenia
Eczema
Malignant Lymphoma
IgE

Complement Dysfunction
Pathway Deficiency Outcome

Classical C1, C2, C4 SLE
C2 deficiency = commonest
MBL MBL deficiency infection is patients with other cause of immune impairment
- prems, chemo, HIV, Ab deficiency
Alternative B, I, P deficiency Infection (esp. with encapsulates)
Terminal pathway C5-9 deficiency - Meningococcus
- Pneumococcus
Inability to make MAC - H. influenzae
- Hib
FH of infection
C3 deficiency C3 deficiency Infections as above + SLE
Acquired C3 deficiency due to C3 nephritic factor assoc. with
membranoproliferative (mesangiocapillary) GN
Ix Hereditary Angioedema / C1 Esterase Deficiency

C3, C4 level Auto dominant: commoner than complement deficiencies
CH50: classical pathway Acquired form may be caused by splenic marginal zone lymphoma
AP50: alternative pathway
If CH50 and AP50 both abnormal with normal C3, C4 = final common pathway Pathophysiology
deficiency (C5-9) Serpin that inhibits
C1
F12 of coag cascade
Kallikrein (Cleaves HMWK Bradykinin)
Deficiency bradykinin symptoms
Presentation
Attacks may be ppted by EtOH, emotional stress, exercise.
Angioedema but NO rash and NOT itchy
Skin
Oropharynx asphyxia
GIT nausea, vomiting diarrhoea
C2 and C4 (normal C1 and C3)

Infections Associated With Immune Deficiencies
Antibody Deficiency Cellular Deficiency Combined Deficiency Phagocyte (PMN) Complement
B cell T cell B+T cell Deficiency Deficiency
Viruses Enterovirus CMV, VAZ, HSV, EBV, measles, All
resp viruses
Bacteria Encapsulates: Pneumococcus Mycobacteria As for Ab deficiency S. aureus Encapsulates
Meningococcus Salmonella S. typhi Other Gm+ and Gm- Esp. Meningococcus
Haemophilus Listeria Listeria Mycobacteria
Enterics
Staph. aureus
Pseudomonas
Fungi Candida Candida Candida Candida
Aspergillus Aspergillus Aspergillus
Histoplasma Histoplasma
Crypto Crypto
PCP PCP
Protozoa Giardia lamblia Toxoplasma Toxoplasma
Clinical Respiratory and GI sepsis Systemic viral / fungal infections Systemic viral/fungal Lymphadenitis, skin/mouth Systemic bacterial
infections and infections, liver and lung infections
Early malignancy gastroenteritis abscesses, granulomas Autoimmune disease
Dx of Immune Deficiency
Infections
2 major or 1 major + recurrent minor infections in 1 year
Unusual organisms
Unusual sites
Unresponsive to oral Abx
Chronic infections
Early structural damage
Other
FTT
Skin disease
Chronic diarrhoea
Mouth ulceration
Family Hx

Dermatology
Contents
Malignant and Pre-malignant Skin Lesions ............................................................................................................................... 233
Psoriasis .................................................................................................................................................................................... 234
Eczema ...................................................................................................................................................................................... 235
Pruritus ...................................................................................................................................................................................... 235
Skin Infections ........................................................................................................................................................................... 236
Miscellaneous Skin Disorders ................................................................................................................................................... 237
Acne Vulgaris ............................................................................................................................................................................ 237
Acne Rosacea ........................................................................................................................................................................... 237
Drug Eruptions........................................................................................................................................................................... 238
Infestations ................................................................................................................................................................................ 238
Skin Manifestations of Systemic Disease.................................................................................................................................. 239

Malignant and Pre-malignant Skin Lesions
Malignant Melanoma Squamous Cell Carcinoma
Ulcerated lesion
c hard, raised everted edges
Epidemiology Sun exposed areas
F>M = 1.5:1
UK incidence = 10 000/yr and 2000 deaths/yr Causes
80% in 20yrs Sun exposure: scalp, face, ears, lower leg
May arise in chronic ulcers: Marjolins Ulcer
Features Xeroderma pigmentosa
Asymmetry
Boarder: irregular Evolution
Colour: non-uniform Solar/actinic keratosis Bowens SCC
Diameter > 6mm Lymph node spread is rare
Evolving / Elevation
Rx
Risk Factors Excision + radiotherapy to affected nodes
Sunlight: esp. intense exposure in early years.
Fair skinned (Low Fitzpatrick Skin Type)
no. of common moles Actinic Keratoses
+ve FH Irregular, crusty warty lesions.
age Pre-malignant (~1%/yr)
Immunosuppression
Rx
Classification Cautery
Superficial Spreading: 80% Cryo
Irregular boarders, colour variation 5-FU
Commonest in Caucasians
Imiquimod
Grow slowly, metastasise late = better prognosis
Photodynamic phototherapy
Lentigo Maligna Melanoma
Often elderly pts.
Face or scalp
Acral Lentiginous Bowens Disease
Asians/blacks Red/brown scaly plaques
Palms, soles, subungual (c Hutchinsons sign) SCC in situ
Nodular Melanoma
All sites Rx
Younger age, new lesion As for AKs
Invade deeply and metastasis early = poor prog
Amelanotic
Atypical appearance delayed Dx Keratoacanthoma
A well differentiated SCC that arises in a hair follicle.
Staging and Prognosis Fast-growing, dome-shaped c a keratin plug.
Breslow Depth Usually regress but may be excised
Thickness of tumour to deepest point of dermal
invasion
<1mm = 95-100% 5ys Basal Cell Carcinoma
>4mm = 50% 5ys Commonest cancer
Clarks Staging Pearly nodule c rolled telangiectactic edge
Stratifies depth by 5 anatomical levels May ulcerate
Stage 1: Epidermis
Typically on face in sun-exposed area
Stage 5: sc fat
Above line from tragus angle of mouth
Metastasis
Behaviour
Liver
Low-grade malignancy very rarely metastasise
Eye
Locally invasive
Mx
O
Excision + 2 margin excision depending on Bres depth Rx
lymphadenectomy Excision
Mohs: complete circumferential margin
adjuvant chemo (may use isolated limb perfusion)
assessment using frozen section histology
Poor prognostic indicators Cryo/radio may be used.
Male sex (more tumours on trunk cf females)
mitoses
Satellite lesions (lymphatic spread)
Ulceration
Psoriasis
Epidemiology Mx
Prevalence: 2% of Caucasians
Age: peaks in 20s and 50s Education
Sex: F=M Avoid triggers
Genetics: 30% have FH
Genetic predisposition Soap Substitute
Aqueous cream
Pathology Dermol cream
TIV hypersensitivity reaction Epaderm ointment
Epidermal proliferation
T-cell driven inflammatory infiltration Emollients
Histo Epaderm
Acanthosis: thickening of the epidermis Dermol
Parakeratosis: nuclei in stratum corneum Diprobase
Munros microabscesses: neutrophils
Topical Therapy
Triggers Vit D3 analogue: e.g. calcipotriol
Stress Steroids: e.g. betamethasone
Dovobet = Calcipotriol + betamethasone
Infections: esp. streps
Tar: mainly reserved for in-patient use
Skin trauma: Kobner phenomenon
Dithranol
Drugs: -B, Li, anti-malarials, EtOH
Retinoids: e.g. tazarotene
Smoking
UV Phototherapy
Signs Causes local immunosuppression
Narrow band UVB
Plaques
Psoralen + UVA: PUVA
Symmetrical well-defined red plaques c silvery scale
Psoralen is a photsensitising agent and can be
Extensors: elbows, knees topical or oral
Flexures (no scales): axillae, groins, submammary PUVA is more effective but skin Ca risk
Scalp, behind ears, navel, sacrum
Non-Biologicals
Nail Changes (in 50%) Methotrexate
Pitting Ciclosporin
Onycholysis Acetretin (oral retinoid / vit A analogue)
Subungual hyperkeratosis SE: lipids, glucose
10-40% Develop Seronegative Arthritis Biologicals

Mono-/oligo-arthritis: DIPs commonly involved Infliximab
Rheumatoid-like Etanercept
Asymmetrical polyarthritis Adalimumab
Psoriatic spondylitis
Arthritis mutilans
May dactylitis
Variants
Guttate
Drop-like salmon-pink papules c fine scale
Mainly on trunk
Occurs in children assoc.
c strep infection
Pustular
Sterile pustules
May be localised to palms and soles
Erythroderma and Generalised Pustular

Generalised exfoliative dermatitis
Severe systemic upset: fever, WCC, dehydration
May be triggered by rapid steroid withdrawal
Differential
Eczema
Tinea: asymmetrical
Seborrhoeic dermatitis
Eczema
Presentation Mx of Atopic Eczema
Extremely itchy
Poorly demarcated rash Education
Acute: oozing papules and vesicles Avoid triggers: e.g. soap
Subacute: red and scaly
Chronic eczema lichenification Soap Substitute
Skin thickening
c exaggeration of skin markings Aqueous cream
Dermol cream
Epaderm ointment
Pathology
Emollients
Epidermal spongiosus
Epaderm
Dermol
Diprobase
Atopic Eczema Oilatum (bath oil)
TH2 driven inflammation c IgE production
Affects 2% of infants Topical Therapy
Most children grow-out of it by 13yrs Steroids
1% Hydrocortisone: face, groins
Cause Eumovate: can use briefly (<1wk) on face
FH of atopy common Betnovate
Specific allergens Dermovate: very strong, brief use on thick skin
House dust mite Palms, soles
Animal dander
Diet: e.g. dairy products 2
nd
line Therapies
Topical tacrolimus
Presentation Phototherapy
Face: esp. around eyes, cheeks Ciclosporin or azathioprine
Flexures: knees, elbows
O
May become 2 infected
Staph fluclox
HSV aciclovir
Pruritus
Associations
Generalised
Asthma
CRF
Hay fever
Cholestasis
Ix Haematological
Polycythaemia
IgE
Hodgkins
RAST testing: identify specific Ag
Leukaemia
Iron deficiency
Endocrine
Irritant Contact Dermatitis DM
Everyone is susceptible to irritants Hyper- / hypo-thyroidism
Causes: detergents, soaps, oils, solvents, venous stasis Pregnancy
Very Itchy Dermatological Diseases

Allergic Contact Dermatitis Eczema
Type IV hypersensitivity reaction Urticaria
Common allergens Scabies
Nickel: jewellery, watches, coins Dermatitis herpetiformis
Chromates: leather
Lanolin: creams, cosmetics
Location: correlates sharply c allergen exposure
Ix: Patch testing
Adult Seborrhoeic Dermatitis

Red, scaly, rash
Cause: overgrowth of skin yeasts (e.g. malassezia)
Location: scalp (dandruff), eyebrows, cheeks,
nasolabial folds
Rx: mild topical steroids / antifungal
Daktacort: miconazole + hydrocortisone
Skin Infections
Tinea Erysipelas
A superficial mycosis caused by dermatophytes Sharply defined superficial infection by S. pyogenes
Microsporum Often affects the face
Epidermophyton High fever + WCC
Trichophyton Rx
Benpen IV
Presentation Pen V and fluclox PO
Round scaly lesion
Itchy Cellulitis
Central clearing Acute infection of skin and soft tissues
Scalp, body, foot, groin, nails
Cause: -haemolytic Strep + staph. aureus
Rx
Skin: terbinafine or topical ketoconazole / miconazole Presentation
Scalp: griseofulvin or terbinafine Deeper and less well defined than erysipelas
Nails: terbinafine Pain, swelling, erythema and warmth
Systemic upset
lymphadenopathy
Candida
Common Rx
RFs: immunosuppression, Abx, steroid inhalers Empiric: fluclox IV
Confirmed Strep: Benpen or Pen V
Presentation Pen allergic: clindamycin
Pink + white patches
Moist Warts
Satellite lesions Caused by HPV infection
Mouth, vagina, skin folds, toe web
Rx
Rx Expectant
Mouth: nystatin Destructive
Vagina: clotrimazole cream and pessary Topical salicylic acid
Cryotherapy
Podophyllin
Imiquimod
Pityriasis versicolor
Caused by Malassezia furfur
Molluscum
Pox virus
Presentation
Pink papules
c umbilicated central punctum
Common in hot and humid environments
Circular hypo-/hyper-pigmented patches Resolve spontaneaously
Fine white scale
Itchy Herpes Zoster / Shingles
Back of neck and trunk Recurrent VZV infection
Dermatomal distribution of cropping vesicles and crust
Ix Thoracic: 50%
Spaghetti and meatballs appearance
c KOH stain Ophthalmic: 20%
Cornea affected in 50% keratitis, iritis
Rx May post-herpetic neuralgia
Selenium sulphate or ketoconazole shampoos Rx: aciclovir or famciclovir PO if severe
Herpes Simplex
Gingivostomatitis or recurrent genital or oral infections
Impetigo Triggered by infection (e.g. CAP), sunlight and
Contagious superficial skin rash caused by S. aureus immunosuppression
May complicate eczema: eczema herpeticum
Presentation
Grouped painful vesicles on an erythematous base
Age: peak @ 2-5yrs
Rx: acyclovir or famciclovir indicated if
Honey-coloured crusts on erythematous base
immunosuppressed or recurrent genital herpes.
Common on face
Rx Pityriasis Rosea
Mild: topical Abx (fusidic acid, mupirocin) HHV-6/-7
More severe: fluclox PO Herald patch precedes rash, mainly on the trunk

Miscellaneous Skin Disorders Acne Vulgaris
Lichen Planus Pathophysiology
sebum production: androgens and CRH
Skin Presentation P. acnes is a skin commensal that flourishes in the
Flexors: wrists, forearms, ankles, legs anaerobic environment of the blocked follicle
Display Kobner phenomenon inflammation
Purple
Pruritic Presentation
Polygonal Inflammation of pilosebaceus follicles
Planar Comedones (white- or black-heads), papules, pustules
Papules nodules, cysts
Lacy white marks: Wickhams Striae Face, neck, upper chest and back
Lesions Elsewhere Mx
Scalp: scarring alopecia Pt. education
Nails: longitudinal ridges Remember that topical therapy is difficult to apply to the
Mouth: lacy white plaques on inner cheeks back.
Genitals
Mild: topical therapy
Rx Benzoyl peroxide
Mild: topical steroids Erythromycin, Clindamycin
Severe: systemic steroids Tretinoin / Isotretinoin
Moderate
Bullous Pemphigoid Topical benzoyl peroxide + oral Abx (doxy or erythro)
Autoimmune blistering disease due to auto-abs against
hemidesmosomes Severe
Isotretinoin (vitamin A analogue)
Presentation 60-70% have no further recurrence
Mainly affects the elderly SE: teratogenic, hepatitis, lipids, depression, dry
Tense bullae on erythematous base skin, myalgia
Can be itchy Monitor: LFTs, lipids, FBC
May try Dianette in women
Ix
Biopsy shows linear IgG along the BM and subepidermal
bullae Acne Rosacea
Chronic relapsing remitting disorder affecting the face
Rx
Clobetasol (Dermavate) Presentation
Chronic flushing ppted. by alcohol or spicy foods.
Fixed erythema: chin, nose, cheeks, forehead
Pemphigus Vulgaris Telangiectasia, papules, pustules (no comedones)
Autoimmune blistering disease due to auto-abs against
desmosomes. Associations
May be ppted by drugs Rhinophyma: swelling and soft tissue overgrowth of the
NSAIDs nose in males
ACEi Blepharitis: scaling and irritation at the eyelashes
L-dopa
Rx
Presentation Avoid sun exposure
Younger pts. Topical azelaic acid
Large flaccid bullae which rupture easily Oral doxycycline or azithromycin
Nikolskys sign +ve
Mucosa is often affected
Ix
Intraepidermal bullae
Rx
Prednisolone
Rituximab
IVIg

Drug Eruptions Infestations
Maculopapular Scabies
Commonest type Sarcoptes scabei
Generalized erythematous macules and papules Highly contagious: spread by direct contact
fever and eosinophils Female mite digs burrows and lays eggs
Develops w/i two weeks of onset of drug
Penicillins, cephalosporins, AEDs Presentation
Burrows: short, serpiginous grey line, block dot
Hypersensitivity rash: eczematous, vesicles
Urticaria Extremely itchy escoriation
st
Wheals angioedema and anaphylaxis Particularly affects the finger web spaces (esp. 1 )
Rapid onset after taking drug Also: axillae, groin, umbilicus
Immune (IgE)
Penicillins Mx
Cephalosporins Permethrin cream: applied from neck down for
Non-immune (direct mast cell degranulation) 24hrs
Morphine 2nd line: Malathion
Codeine 3rd line: oral ivermectin
NSAIDs Treat all members of the household
Contrast
Headlice
Erythema Multiforme Pediculus humanus capitis
Symmetrical target lesions on palms, soles and limbs Spread by head to head contact
Occurs 1-2wks after insult Nits = empty eggs
Infections are commoner cause of EM
Presentation
Causes Itch
Idiopathic Papular rash @ the nape of the neck
Infections: HSV, mycoplasma
Rx
Drugs
Sulphonamides, NSAIDs, allopurinol, penicillin Malathion
phenytoin Combing
Stevens-Johnson Syndrome
More severe variant of EM,
Blistering mucosa: conjunctiva, oral, genital
Toxic Epidermal Necrolysis

Extreme form of SJS
Nearly always a drug reaction
Features
Severe mucosal ulceration
Widespread erythema followed by epidermal necrosis
c loss of large sheets of epidermis

dehydration
risk in HIV+
Rx: dexamethasone, IVIg
Mortality: 30%

Skin Manifestations of Systemic Disease
Skin Conditions Diseases
Erythema Nodosum Disease Skin Manifestation
Painful blue-red lesions on anterior shins Rheumatic fever Erythema marginatum
3 Ss: sarcoid, strep infections and sulfonamides Lyme Erythema chronicum migrans
Also: OCP, IBD and TB, Behcets (Borrelia burgdorferi)
Crohns Perianal ulcers and fistulae
Erythema Multiforme EN
Symmetrical target lesions on palms, soles and limbs Pyoderma gangrenosum
Possibly mediated by IgM deposition Dermatomyositis Heliotrope rash on eyelids
O
Usually 2 to infection Shawl sign (macular rash)
Infections: HSV (70%), mycoplasma Gottrons Papules
Drugs: SNAPP Mechanics hands
Nailfold erythema, telangiectasia
Stevens-Johnson Syndrome and TEN DM Ulcers
Severe variants of EM Candida
Nearly always drug-induced Kyrle disease
Fever, mucosal and skin ulceration and necrosis Acanthosis nigricans
Necrobiosis lipoidica (shins)
Pyoderma Gangrenosum Granuloma annulare (hands, feet)
Wide (10cm), deep ulceration c violaceous border Sarcoidosis Erythema nodosum
Erythema multiforme
Purulent surface
Lupus pernio
Undermined edge Hypopigmented areas
Commonly occurs on legs Red/violet plaques
Heal
c cribriform (pitted) scars Coeliac Dermatitis herpetiformis (elbows)
Assocs.: IBD, AIH, Wegeners, RA, leukaemia Graves Pre-tibial myxoedema (lat mal)
Rx: High-dose systemic steroids RA Rheumatoid nodules
Vasculitis (palpable purpura)
Vitiligo SLE Facial butterfly rash
Chalky white patches
c hyperpigmented borders Systemic sclerosis Calcinosis
Itch in sunlight Raynauds
Assocs.: autoimmune disorders Sclerodactyly
Telangiectasia
Livedo Reticularis Generalised skin thickening
Persistent mottled red/blue lesions that dont blanch Liver disease Palmar erythema
Commonly found on the legs Spider naevi
Triggered by cold Gynaecomastia
Causes 2O sexual hair
Idiopathic Jaundice
Vasculitis: RA, SLE, PAN Bruising
Obstruction: anti-phos, cryoglobulinaemia Excoriations
Sneddons syn.: LR + CVAs ESRD Assoc. c Cause
- DM, vasculitis, sclero, RA, SLE
Assoc. c ESRD
- Pruritus, xerosis, pigment change
Bullous disease
Assoc. c Transplant
- Cushingoid, gingival hyperplasia,
Infections, BCC, SCC, melanoma
Kaposis
Neoplasia Acanthosis nigricans

Dermatomyositis
Thrombophlebitis migrans
Acquired ichthyosis

Epidemiology
Contents
Health Information ..................................................................................................................................................................... 241
Public Health Issues .................................................................................................................................................................. 242
Clinical Evidence ....................................................................................................................................................................... 243
Epidemiological Concepts ......................................................................................................................................................... 244
Disease Prevention ................................................................................................................................................................... 245
Likelihood Ratios ....................................................................................................................................................................... 245

Health Information
Routine Data Clinical Governance
Data that are routinely collected and recorded in an on-
going systematic way, often for administrative purposes. Definition
A transparent system for the continual maintenance and
Advantages improvement of healthcare standards both on an
Relatively cheap individual and organisational level within the NHS.
Already collected and available
Standardised collection procedures Elements
Education and Training
Disadvantages Clinical audit
May not answer the question Clinical effectiveness
Variable quality Research and Development
Not every case captured Openness
Risk Management
Sources
Demographics: census Agencies
Health: births, deaths, admissions, prescriptions, hospital The Care Quality Commission
episode statistics, cancer Independently inspect healthcare services
Exposures: smoking, air pollution, crime against standards set by the Department of
Disease prevention: screening, immunisation uptake Health.
Investigate serious failures in healthcare
services.
Publish regular ratings of NHS trusts.
Hospital Episode Statistics
Electronic record of every inpatient or day-case episode
of patient care in every NHS hospital. Clinical Audit
300 fields of information, including: Are pts. given the best care?
Pt demographics
Diagnosis using ICD-10 Definition
Procedures using OPCS4 A quality improvement process that seeks to improve
pt. care and outcomes through the systematic review of
Advantages care against explicit criteria and the implementation of
Comprehensive change.
Unbiased
Based on case notes
Disadvantages Outcome Measures

Data may not be complete Are pts. better and do they feel better?
In-hospital death only
Patient Reported Outcomes (PROMs)
Calculate the health gain from the pts. perspective after
surgical Rx using pre- and post-operative surveys.
Mortality Arthroplasty, hernia repairs, varicose veins
Hip replacement gives largest improvement in
UK specific condition and general health.
1. Heart and Circulatatory disorders: 33%
a. IHD (23%) Quality and Outcomes Framework (QOF)
b. Stroke (10%) Voluntary annual reward and incentive programme for
2. Cancer: 30% all GP surgeries in England, detailing practice
a. Trachea, bronchus, lung achievement results.
b. Breast, prostate
c. Colorectum
3. Respiratory disorders: 13%
a. Pneumonia
b. COPD
Worldwide
1. IHD
2. Stroke and other cerebrovascular disease
3. LRTI
4. COPD
5. Diarrhoeal diseases

Public Health Issues
Major Contributions to Health Smoking
Drugs and medical intervention Commonest cause of preventable death in the UK
Obstetric and perinatal care 2nd hand smoking
Immunisation Respiratory infections
Screening Asthma
Chronic disease Mx SIDS
lung Ca and CHD risk
Social gradient in mortality is partially explained by
social gradient in smoking.
Major Mortality Risk Factors
Heart and Circulatory Disorders Some Strategies
Smoking
Health education
exercise
Restrict advertising
Diet: fat, calorie, salt, EtOH
?Stress Remove from display in shops
Neoplasms price
Smoking Smoking ban in public places
exercise Very brief advice
Diet: fruit and veg, fibre, fat
Pulmonary Disease
Smoking Alcohol
exercise 5% of men and 2% of women report problems
Occupation: asbestos, dust exposure Recommended
Men: 21u/wk or 3-4u/d
Women: 14u/wk or 2-3u/d
Major Public Health Issues NB. 1u = 10ml EtOH
Smoking
Some Strategies
Obesity / unhealthy diet
National Alcohol Harm Reduction Strategy
Exercise
minimum price / unit
EtOH abuse
Sexual health
Mental health
Mental Health
Common: ~15% lifetime risk
Depression and anxiety disorders most commonly
Obesity
20% obese Some Strategies
50% of females overweight or obese GPs get rewarded for depression screening
Expansion of psychological therapies (e.g. CBT)
Nurses Health Study
Overwt. 3yrs of life
Obese 7yrs of life
Active lifestyle (30min walk/d) prevents 30% of obesity
and 45% of new DM.
Evidence for Changing Nutrition

Mediterranean diet can cardiac death post-MI
Low Na diet BP
Sexual Health
10% of 16-24yr olds have 1 STI
in urban areas and amongst Blacks and Minorities
infertility, ectopics, Cervical Ca, HIV
Some Strategies
Improving access to sexual health services
Chlamydia screening

Clinical Evidence
Hierarchy of Evidence Cohort Study
1. Systematic reviews and meta-analyses Prospective study comparing development of disease in
2. RCTs exposed and non-exposed grps.
3. Cohort or case-control studies Incidence of disease in each grp relative risk
4. Descriptive studies
5. Case reports Examples
Million Women study
Study Types Framingham Heart Study
Nurses Health Study
Observational
Analytical / Aetiological Advantages
Studies determinants of disease by judging Good for evaluation of rare exposures
whether exposure causes or prevents disease Can examine multiple effects of a single exposure
Descriptive Can elucidate temporal relationship
Studies distribution of disease Direct incidence calculation
Person, place and time
Disadvantages
Experimental Inefficient for evaluation of rare diseases
RCTs Expensive and time-consuming
Loss to f/up affects results
Descriptive Studies
Can be used to generate hypotheses RCTs
Provide frequency data Planned experiment designed to assess the efficacy of
Incidence an intervention.
Point prevalence Randomisation: selection bias.
Cant determine causation Blinding: measurement bias
Examples Advantages
Cross-sectional Surveys Most reliable demonstration of causality
Household interview surveys asking questions
regarding illness, social circumstances and Disadvantages
demographics. Non-compliance
Cross-sectional Census Loss to f/up
Ecological studies Validity depends on quality of study
Use populations rather than individual as unit of Ethical issues
observation. Selection criteria may limit generalisability
Subject to significant confounding: age, sex, SES
Other routine data
Meta-Analyses
Observational study of evidence
Case-Control Studies Systematic identification of relevant trials and
Retrospective study of exposure in a case grp
c the assessment of their quality
disease and a control grp w/o the disease. Allow accurate interpretation of multiple RCTs
Proportion of exposed in each group odds ratio
Forest plots
Advantages Square = OR
Quick and cheep Size = size of study
Well-suited for diseases
c long latent periods Line = 95% CI of OR
Good for evaluation of rare diseases Diamond = combined odds ratio
Can examine multiple aetiological factors for a single Width = 95% CI
disease.
Disadvantages
Inefficient for evaluating rare exposures
Cannot calculate incidence rates
Temporal relationship between exposure and disease
can be difficult to establish
Recall bias
E.g. testicular cancer sufferers more likely to
report preceding trauma
Selection bias
E.g. non-random selection of study grps.

Epidemiological Concepts
5 Steps of EBM Odds Ratio
1. Question
2. Search OR = odds of exposure in cases / odds of exposure in controls
3. Appraise = (A/C) / (B/D) = AD/BC
4. Apply
5. Evaluate Case Control
Exposed A B
Association and Causation Not Exposed C D
Association: a relationship between two factors
Causation: X Y OR = ~RR if disease is rare (<10%)
Bradford Hill Causation Criteria Relative Risk

Strong association: i.e RR or OR / in probability of disease given a particular RF
Consistency c other investigations
Specificity RR = incidence in exposed / incidence in unexposed
Temporal relationship = (A/A+B) / (C/C+D)
Dose response relationship
Plausibility Risk Estimates
Coherence Absolute risk: probability of disease occurrence
Experimental evidence Relative risk: / in probability of disease given a RF
Analogy Attributable risk: measure of excess risk due a factor
Chance Number Needed To Treat

Studies are based on estimates from samples and are NNT = (1 / Absolute risk reduction) x 100
therefore subject to random variation. Absolute risk reduction = 1- hazard ratio
Random variation can be minimised by sample size.
The role of chance is assessed by statistical significance Screening
tests and by calculating confidence intervals.
Modified Wilson Criteria
Bias Disease
Inaccurate data due to systematic error in selection, Important health problem
measurement or analysis. Well recognised pre-clinical stage
Natural Hx well understood
Selection Bias Test
Systematic difference between the characteristics of Valid and reliable
those selected for a study and those who were not or Simple and cheap
differences between study grps. Safe and acceptable
E.g. self-selection, healthy worker effect Dx and Rx
Adequate facilities
Measurement Bias Acceptable Rx
Early intervention is of more benefit than later Rx
Occurs when measurements or classifications of
disease or exposure are inaccurate. Cost effective
E.g. inaccuracies of the instruments, expectations of
observers or participants. Validity
Sensitivity: detect true positives
Analysis Bias Specificity: exclude true negatives
Error caused by participants being lost to f/up or PPV: how likely to have disease if positive
switching treatment groups. NPV: how likely not to have disease if negative
Take into account using an intention to treat analysis. PPV and NPV depend on disease frequency
Confounding Disease No Disease

Positive A B PPV
Error in the interpretation of an accurate measurement.
A/(A+B)
Any factor which is prognostically linked to the outcome
Negative C D NPV
and is unevenly distributed between study groups.
C/(C+D)
Not a confounder if it lies on the causal pathway
Sensitivity Specificity
between the variables of interest.
A/(A+C) B/(B+D)
Common confounders: age, sex, SES
Effectiveness
Reducing Confounding
Selection bias: healthiest come for screening
Randomisation
Lead-time bias: disease Dx earlier survival time
Stratification: e.g. stratify by age
Length-time bias: outcome appears better because
Standardisation: e.g. SMR
more disease
c good outcome detected.
Ratio of observed:expected deaths
Expected deaths derived from larger population
Regression
Disease Prevention Likelihood Ratios
Primordial Prevention Pre- and Post-test Probability
Prevention of factors promoting the emergence of risk Pre-: estimate of probability that pt. has a certain
factors: lifestyle, behaviours, exposure patterns disease based on presentation or epidemiology.
Test: diagnostic test or sign or symptom that you elicit
Examples Post-: new probability taking into account the test
Healthy eating programmes in schools result
Social policies to poverty and inequality Likelihood ratio: measure of how much the test alters
Programmes that promote walking, cycling and public your probability of the disease.
transport.
Encouragement of positive health behaviour. Calculation
Odds = probability / (1- probability)

Primary Prevention i.e. the ratio of the probability something will happen to
the probability that it wont.
Prevention of disease onset
Probability = odds / (odds +1)
Examples
Vaccination
LR = p [test result if disease present] / p [test result if disease
Smoking cessation absent]
Healthy diet
Condom use LR for positive test result = sensitivity / (1- specificity)
Detection and Rx of hyperlipidaemia
LR for negative test result = (1- sensitivity) / specificity
Secondary Prevention Post-test odds = pre-test odds x likelihood ratio

Halting progression of established disease
Early detection followed by prompt, effective Rx Example
Pre-test probability could be disease incidence in that
Examples population.
Screening for Ca Convert pre-test probability to odds.
Smoking cessation after MI Calculate likelihood ratio based on the result of your test.
Apply likelihood ratio to get post-test odds.
Convert post-test odds to post-test probability
Tertiary Prevention
Rehabilitation of people
c established disease to
minimise residual disability and complications.
Examples
Rapid Rx of MI or stroke to disability
HAART
Disease Prevention in General Practice

General advice for a healthy lifestyle
Identifying and facilitating reduction of risk factors
Ensuring availability of preventative interventions
Identifying early disease and offering treatment
Prevention Paradox
Many people exposed to a small risk may generate more
disease than a few exposed to a large risk.
when many people receive a small benefit the total
benefit may be large.
However, individual inconvenience may be high to the
many while benefit may only be to a few.
Health Promotion
Process of enabling people to increase control over, and
to improve, their health.
Public policy, supportive environments
Health promotion is specific requirement of the GMC
Good Medical Practice guidelines.

Emergencies
Contents
Shock ......................................................................................................................................................................................... 247
Anaphylactic Shock ................................................................................................................................................................... 248
Narrow Complex Tachycardias = SVT ...................................................................................................................................... 249
Broad Complex Tachycardias ................................................................................................................................................... 250
STEMI ........................................................................................................................................................................................ 251
NSTEMI + UA ............................................................................................................................................................................ 252
Severe Pulmonary Oedema ...................................................................................................................................................... 253
Cardiogenic Shock .................................................................................................................................................................... 254
Meningitis .................................................................................................................................................................................. 255
Encephalitis ............................................................................................................................................................................... 256
Cerebral Abscess ...................................................................................................................................................................... 256
Status Epilepticus ...................................................................................................................................................................... 257
Head Injury ................................................................................................................................................................................ 258
Raised ICP ................................................................................................................................................................................ 259
Signs and Symptoms ................................................................................................................................................................ 259
Acute Severe Asthma ................................................................................................................................................................ 260
Acute Exacerbation of COPD .................................................................................................................................................... 261
Pulmonary Embolism................................................................................................................................................................. 262
Pneumothorax ........................................................................................................................................................................... 263
Upper GI Bleeding ..................................................................................................................................................................... 264
Acute Renal Failure ................................................................................................................................................................... 265
Poisoning: Recognition and Management ................................................................................................................................ 266
Diabetic Ketoacidosis ................................................................................................................................................................ 267
Hyperosmolar Non-Ketotic Coma.............................................................................................................................................. 268
Hypoglycaemia .......................................................................................................................................................................... 268
Thyroid Storm ............................................................................................................................................................................ 269
Myxoedema Coma .................................................................................................................................................................... 269
Addisonian Crisis ....................................................................................................................................................................... 270
Hypertensive Crisis.................................................................................................................................................................... 270
Burns ......................................................................................................................................................................................... 271
Hypothermia .............................................................................................................................................................................. 272
ALS Algorithm............................................................................................................................................................................ 272
Tachycardia Algorithm ............................................................................................................................................................... 272
Bradycardia Algorithm ............................................................................................................................................................... 272

Shock
If ECG unrecordable, Rx as cardiac arrest Causes : CHOD
Cardiogenic
ABCDE MI
Arrhythmia
Hypovolaemic
Raise foot of bed Haemorrhage: internal and external
(unless cardiogenic) Endocrine: Addisonion crisis, DKA
Excess loss: burns, diarrhoea
Third-spacing: pancreatitis
IV Access:
2 wide bore (14g) cannula in each ACF Obstructive
PE
Tension pneumothorax
Fast infusion of crystalloid to raise BP Distributive
(unless cardiogenic) Sepsis
Anaphylaxis
Neurogenic
Assessment
Appearance
History Cold, clammy: cardiogenic or hypovolaemic
Chest pain: MI, PE, dissection, anaphylaxis
Warm, well perfused: septic
Abdo pain: AAA, DKA, peritonitis, ruptured ectopic
Urticaria, angioedema, wheeze: anaphylaxis
Back pain: AAA
Hands JVP
CRT: hypovolaemia, cardiogenic : cardiogenic
: hypovolaemic, distributive
Pulse
Tachy (unless -B or bradyarrhythmia)
Abdomen
Small, thread: hypovolaemia
Tender, guarding: trauma, aneurysm, peritonitis.
Bounding: sepsis
Melaena: GI bleed
ABP
PP: hypovolaemia
R-L differential > 20mmHg: dissection
Ix Specific Measures
FBC, U+E, glucose, ABG, CRP, trop Anaphylaxis:
X-match, clotting Adrenaline (0.5mg), hydrocortisone (200mg), chlorphenamine
Blood cultures, urine MCS (10mg), salbutamol
ECG, CXR, USS, Echo, CT
Cardiogenic:
Rx arrhythmias/MI. Consider dobutamine.
Septic shock:
Monitoring IV Abx (e.g. meropenem 1g/8h IV + tazocin 4.5g/8h IV)
Catheter (>30ml/hr) Fluids, vasopressors (e.g. norad)
Art line
CVP line Hypovolaemic
Fluid replacement: crystalloid, colloid, blood (grp specific/O neg)
Titrate to: urine output, CVP, BP
Haemodialysis if ATN

Anaphylactic Shock
Pathogenesis Mx
Type 1 IgE mediated hypersensitivity reaction
TH2 driven IgE production following 1O allergen exposure Secure Airway and give 100% O2
Re-exposure biphasic inflammatory response Intubate if respiratory obstruction
Elevate the feet
Early phase: w/i minutes
IgE cross-linking mast cell degranulation
Vasoactive mediator release
Histamine Adrenaline 0.5mg IM
Tryptase 0.5ml of adrenaline 1:1000
Lipid mediator synthesis Repeat every 5min if needed
Leukotrienes: vasc perm + bronchial
Guided by cardiorespiratory function
constriction
Prostacyclin
Chemokines: e.g. eotaxin
Promote leukocyte recruitment (esp. eosinophils)
Secure IV Access
Late Phase: 2-24hrs Blood for mast cell tryptase
Eosinophils recruited in early phase. IVI 0.9% NS may be needed
Release enzymes and stimulate mast cells. E.g. 500ml over 15-30min
Amplify and sustain the initial response Titrate against BP
Common Precipitants Chlorphenamine 10mg IV

Drugs: penicillin, contrast media +
Food: peanuts, eggs, fish, semen Hydrocortisone 200mg IV
Latex
Stings
Salbutamol Nebs if wheeze

Presentation 5mg salbutamol + 0.5mg ipratropium
Sweating, d/v
Urticaria, itching, oedema
Wheeze, laryngeal obstruction, cyanosis
Further Mx
Tachycardia, hypotension
Monitor closely for second deterioration.
Possible improvement and then deterioration as late
phase initiates.
Discharge
Teach adrenaline self-injection and ensure pt. has
2 0.3mg Epipens.
Advise wearing of medic alert bracelet
Advice re recognition and avoidance
Arrange OPD f/up
OPD f/up
Skin prick tests may help ID antigens
RAST may be preferable

Narrow Complex Tachycardias = SVT
Definition: Rate >100bmp, QRS width < 120ms Principles of Mx
If pt. compromised sedate + DC cardioversion
Differential Otherwise ID rhythm and Rx accordingly
1. Sinus tachycardia Key to ID irregular rhythm = AF = different Rx
Vagal manoeuvres (carotid sinus massage, valsalva) transiently
2. Atrial AV block and may unmask underlying atrial rhythm.
AF If manoeuvres unsuccessful, give adenosine while recording
Atrial flutter rhythm strip
Atrial tachycardia transient AV block, unmasking atrial rhythm
cardioverts AVNRT/AVRT to sinus rhythm
3. AV nodal re-entry tachycardia If adenosine fails, choose from:
4. AV re-entry tachycardia Digoxin
Atenolol
Verapamil (not if on -blocker)
Amiodarone
If unsuccessful DC cardioversion
Mx Flowchart
O2 + IV access
Regular rhythm? NO Treat as AF

Control rate
c -B (e.g. metoprolol) or digoxin
YES If onset <48h consider cardioversion c amiodarone (as
below) or DC shock
Continuous ECG trace Consider anticoagulation c heparin and/or warfarin
Vagal manoeuvres
Adenosine 6mg IV bolus NB. Avoid adenosine, CCB, -B in AF/Flutter with WPW or Hx of
Then 12mg, then 12mg WPW as may VF. Use Amiodarone or flecainide.
YES
BP <90
HF
consciousness
HR >200 100200360J
NO
Choose from:
Amiodarone:
Digoxin (500ug over 30min)
Amiodarone 300mg over 20-60min
Verapamil Then 900mg over next 23h
Atenolol
Adenosine Prophylaxis
MOA: temporary AVN block -B
SEs: Transient chest tightness, dyspnoea, flushing, headache AVRT: flecainide
Relative CIs: asthma, 2nd/3rd degree block AVNRT: verapamil
Interactions
fx d by dipyridimole
fx d by theophylline

Definition: Rate >100bmp, QRS width > 120ms VT Causes: IM QVICK
Infarction (esp.
c ventricular aneurysm)
Differential Myocarditis
1. VT QT interval
2. Torsades de points Valve abnormality: mitral prolapse, AS
3. SVT
c BBB Iatrogenic: digoxin, antiarrhythmics, catheter
Cardiomyopathy (esp. dilated)
K, Mg, O2, acidosis
Mx Flowchart
Pulse? CPR
NO
YES
O2 + IV access
YES
BP<90
HF
Chest pain
consciousness
HR > 150 200300360
NO
Correct Electrolyte Problems Amiodarone:

K+: max 60mM KCL @ 20mmol/h 300mg over 20-60min
Mg2+: 4ml 50% MgSO4 in 30min Then 900mg over next 23h
Assess Rhythm
Regular (i.e. VT):
Amiodarone (see opposite)
Or lignocaine 50mg over 2min
If irregular, Dx is usually:
AF c BBB
Pre-excited AF: flec / amio Recurrent / Paroxysmal VT
TDP: MgSO4 2g IV over 10 min
Medical:
Amiodarone
Failure
-B
Synchronised Cardioversion
ICD

STEMI
12 lead ECG Primary Percutaneous Coronary Intervention

Rx of choice if <12h
Angioplasty and stenting
+ GP IIb/IIIa antagonist (tirofiban) if high risk
O2 2-4L aim for SpO2 94-98% Delayed PCI, DM, complex procedure
Complications:
Bleeding
IV access Emboli
Bloods for FBC, U+E, glucose, lipids Arrhythmia
Thrombolysis
Brief assessment CI beyond 24hrs from pain onset
Thrombolysis CIs ECG Criteria:
CV exam ST elevation > 1mm in 2+ limbs or > 2mm in 2+ chest leads.
New LBBB
Posterior: Deep ST depression and tall R waves in V1-V3
Antiplatelet Contraindications: AGAINST

Aspirin 300mg PO (then 75mg/d) Aortic dissection
Clopidogrel 300mg PO (then 75mg/d) GI bleeding
Allergic reaction previously
Iatrogenic: major surgery <14d
Neuro: cerebral neoplasm or CVA Hx
Analgesia Severe HTN (200/120)
Morphine 5-10mg IV Trauma, inc. CPR
Metoclopramide 10mg IV st
Agents: 1 : streptokinase, alteplase (rt-PA), tenecteplase
Complications:
Anti-ischaemia Bleeding
GTN 2 puffs or 1 tablet SL Stroke
-B atenolol 5mg IV (CI: asthma, LVF) Arrhythmia
Allergic reaction
DVT Prophylaxis Pts. not receiving any form of reperfusion therapy should be given
Enoxaparin 40mg SC OD fondaparinux.

Admit to CCU for monitoring ACEi: start w/i 24hrs of MI (e.g. lisinopril 2.5mg)
Arrhythmias -blocker: e.g. bisoprolol 1.25mg OD (or, CCB)
Continue meds except CCBs Cardiac rehabilitation (group exercise and info) / Heart Manual
DVT prophylaxis until fully mobile
Continue for 3mo if large anterior MI
Statin: regardless of basal lipids (e.g. atorvastatin 80mg)
Primary PCI or Thrombolysis
Advice
Stop smoking
Diet: oily fish, fruit, veg, sat fats
Exercise: 30min OD
Work: return in 2mo
Sex: avoid for 1mo
Driving :avoid for 1mo
NB. Continue clopidogrel for 1mo following STEMI


NSTEMI + UA
12 lead ECG + Admit to CCU
O2 2-4L aim for SpO2 94-98%
IV access
Bloods for FBC, U+E, glucose, lipids,
Troponin
Brief Assessment
CV exam
Antiplatelet
Aspirin 300mg PO (then 75mg/d)
Clopidogrel 300mg PO
Anti-coagulate
Fondaparinux 2.5mg SC
Analgesia
Morphine 5-10mg IV
Metoclopramide 10mg IV
Anti-ischaemia
GTN: 2 puffs or 1 tablet SL
-B: atenolol 50mg/24h PO (CI: asthma, LVF)
IV GTN if pain continues
Assess Cardiovascular Risk: GRACE/TIMI
Intermediate- to High-Risk Low-Risk

Persistent/recurrent ischaemia, ST depression, DM, No further pain, flat or inverted T waves or normal
positive trop. ECG, negative trop.
GPIIb/IIIa antagonist (tirofiban) May discharge if 12h trop is negative.
Angiography (PCI) w/i 96hrs Outpatient tests: angio, perfusion scan, stress echo
Clopidogrel 75mg/d for one year

ACEi (e.g. lisinopril 2.5mg)
-blocker (e.g. bisoprolol 1.25mg OD) or,
CCB (diltiazem or verapamil)
Stop antithrombotic therapy when pain free (but give 3-5d)
Statin (e.g. atorvastatin 80mg)
Advice as above
NB. Continue clopidogrel for 1yr following NSTEMI
Severe Pulmonary Oedema
Sit pt. up Causes
Cardiogenic
MI
O2
Arrhythmia
15L/min via reservoir mask
Fluid overload: renal, iatrogenic
Target SpO2: 94-98%
Non-cardiogenic
ARDS: sepsis, post-op, trauma
IV access + monitor ECG Upper airway obstruction
Bloods for FBC, U+E, troponin, BNP, ABG Neurogenic: head injury
Rx any arrhythmias (e.g. AF)
Symptoms
Dyspnoea
Diamorphine 2.5-5mg IV Orthopnea
+ Metoclopramide 10mg IV Pink frothy sputum
Frusemide 40-80mg IV Signs

Distressed, pale, sweaty, cyanosed
HR, RR
JVP
GTN 2 puffs or 2 x 300ug tabs SL
S3 / gallop rhythm
Unless SBP <90mmHg
Bibasal creps
Pleural effusions
Hx, Ex, Ix
CXR: ABCDE
ECG: MI, arrhythmias, pulsus alternans Differential
Consider echo Asthma/COPD
Pneumonia
PE
If SBP >100mmHg, start nitrate IVI
ISMN 2-10mg/h IVI
Keep SBP >90 Monitoring Progress
BP
HR and RR
If worsening, consider: JVP
CPAP Urine Output
More frusemide or nitrate infusion ABG
Haemofiltration / dialysis
If SBP <100mmHg: Rx as cardiogenic shock

i.e. consider inotropes
Continuing Therapy
Daily weights
DVT prophylaxis
Repeat CXR
Change to oral frusemide or bumetanide
ACEi + -B if heart failure
Consider spironolactone
Consider digoxin warfarin (esp. if in AF)
Morphine in Pulmonary Oedema

Make pt. more comfortable
Pulm venodilators pre-load optimise position on Starling Curve
Cardiogenic Shock
O2 Definition
15L/min via reservoir mask Inadequate tissue perfusion primarily due to
Target SpO2: 94-98% cardiac dysfunction.
Causes: MI HEART:
IV access + monitor ECG MI
Bloods for FBC, U+E, troponin, ABG Hyperkalaemia (inc. electrolytes)
Endocarditis (valve destruction)
Aortic Dissection
Diamorphine 2.5-5mg IV (pain/anxiety) Rhythm disturbance
+ metoclopramide 10mg IV Tamponade
Obstructive
Tension pneumo
Correct any:
Massive PE
Arrhythmias
Electrolyte disturbance
Acid-base abnormalities Presentation
Unwell: pale, sweaty, cyanosed, distressed
Cold clammy peripheries
Hx, Ex, Ix RR HR
CXR Pulmonary oedema
Echo
Consider CT thorax (dissection/PE)
Monitoring
CVP, BP, ABG, ECG, urine output.
Consider need for dobutamine
Rx underlying cause
Tamponade
Causes: Signs: Ix:

Trauma Becks triad: BP, JVP, muffled heart sounds Echo: diagnostic
Lung/breast Ca Kussmauls sign: JVP on inspiration CXR: globular heart
Pericarditis Pulsus paradoxus (pulse fades on inspiration)
MI
Bacteria (e.g. TB)
Mx:
ABCs
Pericardiocentesis (preferably under echo guidance)

Meningitis
Features
Abx Therapy
Meningitic Community: benpen 1.2g IV/IM
Headache <50: ceftriaxone 2g IVI/IM BD
Neck stiffness >50: ceftriaxone + ampicillin 2g IVI /4h
c hip @ 90O
Kernigs: Straightening leg If viral suspected: aciclovir
Brudzinskis: lifting head lifting of legs
Photophobia Organisms
n/v Viruses: enteroviruses (Coxsackie, echovirus), HSV2
Meningococcus
Neurological
Pneumococcus
GCS coma
Listeria
Seizures (20%)
Haemophilus
Focal neuro (20%): e.g. CN palsies
TB
Cryptococcus
Septic
Fever
BP, HR Ix
CRT Bloods: FBC, U+Es, clotting, glucose, ABG
Purpuric rash Blood cultures
DIC LP: MCS, glucose, virology/PCR, lactate
Acute Management
ABC
O2 15L SpO2 94-98%
IVI fluid resus
c crystalloid
Mainly Septicaemic Mainly Meningitic

Dont attempt LP If no shock or CIs do LP
Ceftriaxone 2g IVI Dexamethasone 0.15mg/kg IV QDS
Consider ITU if shocked Ceftriaxone 2g IVI post-LP
Continuing Management
Ceftriaxone 2g BD IVI
Meningococcus: 7d IV then review
Pneumococcus: 14d IV then review
Maintenance fluids
UO 30ml/h
SBP >80mmHg
If response is poor, consider intubation inotropic support
Rifampicin prophylaxis for household contacts.
CIs to LP: Try LP Unless ContraINdicated CSF Findings

Thrombocytopenia
Lateness (delay in antibiotic admin)
Pressure (signs of raised ICP)
Cells PMN Lympho / Lympho /
Unstable (Cardio + resp systems) mononuc mononuc
Coagulation disorder Count 100-1000 10-1000 50-1000
Infection at LP site Glucose (< (< > plasma
Neurology (focal neurological signs) plasma) plasma)
Protein (g/L) (>1.5) (1-5) mild (<1)

Encephalitis Cerebral Abscess
Presentation Pre-disposing Factors
Infectious prodrome: fever, rash, LNs, cold sores, Infection: ear, sinus, dental or periodontal
conjunctivitis, meningeal signs. Skull #
Bizarre behaviour or personality change Congenital heart disease
Confusion Endocarditis
GCS coma Bronchiectasis
Fever Immunosuppression
Headache
Focal neuro Organisms
Seizures Frontal sinus/teeth strep. Milleri, oropharyngeal
Hx of travel or animal bite anaerobes
Ear Bacteroides, other anaerobes
Causes
Signs
Usually viral Seizures
HSV1/2 Fever
CMV, EBV, VZV Localizing signs
Arboviruses Signs of ICP
HIV Signs of infection elsewhere
Non-viral Ix
Any bacterial meningitis CT/MRI ring-enhancing lesion
TB WCC, ESR
Malaria
Lyme disease
Rx
Neurosurgical referral
Ix Abx e.g. ceftriaxone
Bloods: cultures, viral PCR, malaria film Treat ICP
Contrast CT: focal bilat temporal involvement suggests
HSV
LP: CSF protein, lymphocytes, PCR
EEG: shows diffuse abnormalities, may confirm Dx
Mx
Aciclovir STAT: 10mg/kg/8h IVI over 1h for 14/7
Supportive measures in HDU/ITU
Phenytoin for seizures
Prognosis
70% mortality if untreated
w/o fever, consider encephalopathy

glucose
Hepatic
DKA
Drugs
SLE
Uraemia
Hypoxic brain injury
Beri-Beri

Status Epilepticus
Definition Drugs
Seizure lasting >30min, or
Repeated seizures w/o intervening consciousness Lorazepam
2-4mg IV bolus over 30s
Ix 2nd dose if no response w/i 2min
BM Alternatives:
Diazepam 10mg IV/PR (20mg max)
Bloods: glucose, ABG, U+E, FBC, Ca2+
Midazolam 10mg buccal
ECG, EEG
Consider: AED levels, tox screen, LP, hCG, CT Phenytoin
18mg/kg IVI @ 50mg/min
100mg/6-8h maintenance
Monitor ECG and BP
CI: bradycardia or heart block
Diazepam Infusion
100mg in 500ml 5% dex @ 40ml/hr (3mg/kg/24h)
Dexamethasone
10mg IV if vasculitis / cerebral oedema (tumour)
possible
Acute Management
ABC
Oral / nasal airway, intubate
Suction
100% O2
Capillary blood glucose
IV Access + Bloods
U+E, LFT, FBC, Glucose, Ca2+
AED levels
Tox screen
Reverse Potential Causes

Thiamine 250mg IV if EtOH
100ml 20% glucose unless glucose
known to be normal
Slow IV Bolus Phase

Lorazepam 2-4mg IV
2nd dose if no response w/i 2min
IV Infusion Phase
Phenytoin 18mg/kg IVI (then 100mg/6-8h)
Or, diazepam 100mg in 500ml 5% dex IVI
RSI Phase
Never spend >20min c someone in status w/o
getting an anaesthetist

Head Injury
Initial Mx Intubate
GCS 8
1O Survey PaO2 <9KPa on air / <13KPa on O2 or PCO2 >6KPa
A: ? intubation, immobilise C-spine Spontaneous hyperventilation: PCO2 <4KPa
B: 100% O2, RR Respiratory irregularity
C: IV access, BP, HR
D: GCS, pupils CT head guidelines: BANGS LOC
Treat seizures Break: open, depressed or base of skull
Lorazepam 2-4mg IV Amnesia > 30min retrograde
Phenytoin18mg/kg IVI then 100mg/6-8h Neuro deficit or seizure
E: expose pt. and look for other obvious injuries GCS: <13 @ any time or <15 2h after injury
Sickness: vomited > once
2O Survey LOC or any amnesia and any of:
Look for: Dangerous mechanism: RTA, great height
Lacerations Age 65
Obvious facial/skull deformity Coagulopathy (inc. warfarin)
CSF leak from nose or ears
Battles sign, Racoon eyes
Blood behind TM
Risk of Intracranial Haematoma in Adults:
C-spine tenderness deformity Fully conscious, no skull # = <1:1000
Head-to-toe examination for other injuries Confused, no skull # = 1:100
Log role Fully conscious, skull # = 1:30
Confused, skull # = 1:4
Hx if possible
How and when? GCS
GCS and other vitals immediately after injury
Headache, fits, vomiting, amnesia, EtOH Eyes: 4
4 Spontaneous eye opening
Ix 3 Open to voice
Bloods: FBC, U+E, glucose, clotting, EtOH level, ABG 2 Open to pain
? CT head + c-spine 1 No opening
Verbal: 5
Rx 5 Orientated conversation
Neurosurgical opinion if signs of ICP, CT evidence of 4 Confused conversation
intracranial bleed significant skull # 3 Inappropriate speech
Admit if: 2 Incomprehensible sounds
Abnormalities on imaging 1 No speech
Difficult to assess: EtOH, post-ictal
Not returned to GCS 15 after imaging Motor: 6
CNS signs: vomiting, severe headache 6 Obeys commands
Neuro-obs half-hrly until GCS 15 5 Localises pain
GCS 4 Withdraws to pain
Pupils 3 Decorticate posturing to pain (flexor)
HR, BP 2 Decerebrate posturing to pain (extensor)
RR, SpO2 1 No movement
Temperature
Discharge Advice
Stay with someone for first 48hrs
Give advice card advising return on:
Confusion, drowsiness, unconsciousness
Visual problems
Weakness
Deafness
V. painful headache that wont go away
Vomiting
Fits

Raised ICP
Types of Cerebral Oedema
1. Vasogenic ( cap permeability): trauma, tumour, ischaemia, infection
2. Cytotoxic: e.g. from hypoxia
3. Interstitial: e.g. obstructive hydrocephalus, Na+
Causes Acute Management

Haemorrhage
ABC
Tumours
Infection: meningitis, encephalitis, abscess
Hydrocephalus
Status Treat seizures and correct hypotension
Cerebral oedema
Signs and Symptoms Elevate bed to 40O

Headache
n/v
Seizures Neuroprotective Ventilation
Drowsiness coma PaO2: >13kPa (100mmHg)
Cushings reflex: BP, HR, irregular breathing PCO2: 4.5kPa
6th CN palsy (may be false localising) Good sedation NM blockade
Cheyne-Stokes respiration
Pupils constriction dilatation
Papilloedema, loss of venous pulsation @ disc
Mannitol or Hypertonic Saline
ICP short-term, but may rebound ICP later
Mannitol 1g/kg (20% @ 5ml/kg)
Herniation Syndromes
Tonsillar (Coning)
pressure in posterior fossa displacement of cerebellar tonsils through foramen magnum
compression of brainstem and cardioresp centres in medulla
CN6 palsy, upgoing plantars irregular breathing apnoea
Transtentorial / uncal
Lateral supratentorial mass compression of ipsilateral inferomedial temporal lobe (uncus) against free margin of
tentorium cerebelli.
Ipsilateral CN3 palsy: mydriasis (dilation) then down-and-out
Contralateral hemiparesis
Compression of contralateral corticospinal tracts ipsilateral hemiparesis (Kernohans Notch)
Subfalcine
Frontal mass
Displacement of cingulate gyrus (medial frontal lobe) under falx cerebri
Compression of ACA stroke
Contralateral motor/sensory loss in legs>arms
Abulia (pathological laziness)

Acute Severe Asthma
Presentation Mx
Acute breathlessness and wheeze
O2, Nebs and Steroids
Hx 1. Sit-up
Precipitant: infection, travel, exercise? 2. 100% O2 via non-rebreathe mask (aim for 94-98%)
Usual and recent Rx? 3. Nebulised salbutamol (5mg) and ipratropium (0.5mg)
Previous attacks and severity: ICU? 4. Hydrocortisone 100mg IV or pred 50mg PO (or both)
Best PEFR? 5. Write no sedation on drug chart
Ix
PEFR If Life Threatening
ABG Inform ITU
PaO2 usually normal or slightly MgSO4 2g IVI over 20min
PaCO2 Nebulised salbutamol every 15min (monitor ECG)
If PaCO2 : send to ITU for ventilation
FBC, U+E, CRP, blood cultures
If Improving
Assessment Monitor: SpO2 @ 92-94%, PEFR
Continue pred 50mg OD for 5 days
Severe
Nebulised salbutamol every 4hrs
PEFR <50%
RR >25
HR >110
Cant complete sentence in one breath IV Rx if No Improvement in 15-30min:
Nebulised salbutamol every 15min (monitor ECG)
Life Threatening Continue ipratropium 0.5mg 4-6hrly
PEFR <33% MgSO4 2g IVI over 20min
SpO2 <92%, PCO2 >4.6kPa, PaO2 <8kPa Salbutamol IVI 3-20ug/min
Cyanosis Consider Aminophylline
Hypotension Load: 5mg/kg IVI over 20min
Exhaustion, confusion Unless already on theophylline
Silent chest, poor respiratory effort Continue: 0.5mg/kg/hr
Tachy-/brady-/arrhythmias Monitor levels
ITU transfer for invasive ventilation
Differential
Acute exacerbation of COPD
Pneumothorax
Pulmonary oedema Monitoring
PEFR every 15-30min
Pre- and post- agonist
Admission Criteria
SpO2: keep >92%
Life-threatening attack
ABG if initial PaCO2 normal or
Feature of severe attack persisting despite initial Rx
May discharge if PEFR > 75% 1h after initial Rx
Discharge When
Been stable on discharge meds for 24h
PEFR > 75% c diurnal variability < 25%
Discharge Plan
TAME pt.
PO steroids for 5d
GP appointment w/i 1 wk.
Resp clinic appointment w/i 1mo

Acute Exacerbation of COPD
Causes
Viral URTI (30%) Management
Also bacterial infections
Controlled O2 Therapy
Presentation Sit-up
Cough + sputum 24% O2 via Venturi mask: Target SpO2 88-92%,
Breathlessness Vary FiO2 and SpO2 target according to ABG
Wheeze Aim for PaO2 >8 and in PCO2 of <1.5kPa
Hx
Smoking status
Exercise capacity Nebulised Bronchodilators
Current treatment Air driven
c nasal specs
Previous exacerbations Salbutamol 5mg/4h
Ipratropium 0.5mg/6h
Ix
PEFR
Bloods: FBC, U+E, ABG, CRP, cultures
Sputum culture Steroids (IV and PO)
CXR: infection, pneumothorax Hydrocortisone 200mg IV
ECG Prednisolone 40mg PO for 7-14d
Differential
Pneumothorax Abx
Pulmonary oedema If evidence of infection
PE Doxy 200mg PO STAT then 100mg OD PO for 5d
Asthma
Discharge NIV if no response:

Spirometry Repeat nebs and consider aminophylline IV
Establish optimal maintenance therapy Consider NIV (BiPAP) if pH<7.35 and/or RR >30
GP and specialist f/up Consider invasive ventilation if pH<7.26
Prevention using home oral steroids and Abx Depends on pre-morbid state: exercise capacity,
Pneumococcal and Flu vaccine home O2, comorbidity
Home assessment

Pulmonary Embolism
Causes Mx
Usually arise from DVTs in proximal leg or iliac veins
Rarely:
O2
Right ventricle post MI
Sit-up
Septic emboli in right sided endocarditis
100% O2 via non-rebreather mask
Risk Factors: SPASMODICAL
Sex: F
Pregnancy Analgesia
Age: Morphine metoclopramide if distressed
Surgery (classically 10d post-op straining at stool)
Malignancy
Oestrogen: OCP/HRT If critically ill c
massive PE consider thrombolysis
DVT/PE previous Hx
Immobility
Alteplase 50mg bolus stat
Colossal size (Surgical or interventional embolectomy)
Antiphospholipid Abs
Lupus Anti-coagulant
LMWH Heparin
Presentation e.g. enoxaparin 1.5mg/kg/24h SC
Symptoms and signs depend on size, number and
distribution of emboli
Symptoms SBP?
Dyspnoea
Pleuritic pain
Haemoptysis
<90 >90
Syncope
500ml colloid Start Warfarin
Confirm Dx
Signs
Fever
Cyanosis
Tachycardia, tachypnoea Inotropes if BP still
RHF: hypotension, JVP, loud P2 Dobutamine: aim for SBP >90
Evidence of cause: DVT Consider addition of NORAD
Consider thrombolysis (medical or surgical)
Ix
Bloods: FBC, U+E, clotting, D-dimers
ABG: normal or PaO2 and PaCO2, pH On-going Mx
CXR: normal or oligaemia, linear atelectasis
ECG: sinus tachycardia, RBBB, right ventricular strain TEDS stockings in hospital
(inverted T in V1-V4) Graduated compression stockings for 2yrs if DVT:
S1, Q3, T3 is rare prevent post-phlebitic syndrome (10-30%)
Doppler US: thigh and pelvis (+ve in 60%) Continue LMWH until INR >2 (at least 5d)
CTPA + venous phase of legs and pelvis Target INR = 2-3
85-95% sensitivity Duration
V/Q scan no longer used Remedial cause: 3mo
No identifiable cause: 6mo
Dx On-going cause: indefinite
1. Assess probability using Wells Score VC filter if repeat DVT/PE despite anticoagulation
2. Low-probability perform D-dimers
Negative excludes PE
Positive CTPA
3. High probability CTPA
NB. ve D-dimer has 95% NPV for PE
Prevention
Risk assessment for all pts
TEDS
Prophylactic LMWH
Avoid OCP/HRT if @ risk

Pneumothorax
Definition Mx
c 2O lung
Accumulation of air in the pleural space
collapse.
Tension PTX
Resuscitate pt.
Classification No CXR
Closed: intact chest wall and air leaks from lung into Large bore Venflon into 2nd ICS, mid-clavicular line
pleural cavity.
Insert ICD
Open: defect in the chest wall allows communication
between PTX and exterior: may be sucking.
Tension: air enters pleural cavity through one-way Traumatic
valve and cannot escape mediastinal compression. Resuscitate pt.
Analgesia: e.g. morphine
Causes 3-sided wet dressing if sucking
Spontaneous Insert ICD
1O: no underlying lung disease
Young, thin men (ruptured subpleural bulla)
Smokers
1O PTX
2O: underlying lung disease
COPD No
SOB and/or rim 2cm? Consider d/c
Marfans, Ehlers Danlos
Pulmonary fibrosis, sarcoidosis Yes
Yes
Trauma Aspiration successful?

Penetrating
Blunt rib #s No
Iatrogenic Insert ICD

Subclavian CVP line insertion
Positive pressure ventilation
Transbronchial biospy 2O PTX
Liver biopsy Yes
SOB and > 50yrs and Insert ICD
rim 2cm?
Presentation
No No
Symptoms
Sudden onset Aspiration successful?
Dyspnoea
Pleuritic chest pain Yes
Tension: respiratory distress, cardiac arrest
Admit for 24h
Signs
Chest
expansion
Resonant percussion
breath sounds
VR
Tension: JVP, mediastinal shift, HR, BP
Crepitus: surgical emphysema
Ix
ABG
US
CXR (expiratory film may be helpful)
Translucency + collapse (2cm rim = 50% vol
loss)
Mediastinal shift (away from PTX)
Surgical emphysema
Cause: rib #s, pulmonary disease (e.g. bullae)

Upper GI Bleeding
Hx Management
Previous bleeds
Dyspepsia, known ulcers Resuscitate
Liver disease or oesophageal varices Head-down.
Dysphagia, wt. loss 100% O2, protect airway
Drugs and EtOH 2 x 14G cannulae + IV crystalloid infusion up to 1L.
Co-morbidities Bloods: FBC, U+E ( urea), LFTs, clotting, x-match
6u, ABG, glucose
o/e
Signs of CLD
PR:melaena Blood if remains shocked
Shock? Group specific or O- until X-matched
Cool, clammy, CRT>2s
BP (<100) or postural hypotension (>20 drop)
urine output (<30ml/h)
Tachycardia Variceal Bleed
GCS Terlipressin IV (splanchnic vasopressor)
Prophylactic Abx: e.g. ciprofloxacin 1g/24h
Common Causes
PUD: 40% (DU commonly)
Acute erosions / gastritis:20% Maintenance
Mallory-Weiss tear: 10% Crystalloid IVI, transfuse if necessary (keep Hb10)
Varices: 5% Catheter + consider CVP (aim for >5cm H2O)
Oesophagitis: 5% Correct coagulopathy: vit K, FFP, platelets
Ca Stomach / oesophagus:<3% Thiamine if EtOH
Notify surgeons of severe bleeds
Rockall Score: (Prof T Rockall, St. Marys)
Prediction of re-bleeding and mortality
40% of re-bleeders die
Urgent Endoscopy
Initial score pre-endoscopy
Haemostasis of vessel or ulcer:
Age
Adrenaline injection
Shock: BP, pulse
Comorbidities Thermal / laser coagulation
Final score post-endoscopy Fibrin glue
Final Dx + evidence of recent haemorrhage Endoclips
Active bleeding
Variceal bleeding:
Visible vessel
2 of: banding, sclerotherapy, adrenaline,
Adherent clot
coagulation
Initial score 3 or final >6 are indications for surgery
Balloon tamponade c Sengstaken-Blakemore tube
Only used if exsanguinating haemorrhage or
Oesophageal Varices failure of endoscopic therapy
Portal HTN dilated veins @ sites of porto-systemic
TIPSS if bleeding cant be stopped endoscopically
anastomosis: L. gastric and inferior oesophageal veins
30-50% c portal HTN will bleed from varices
Overall mortality 25%:
c severity of liver disease.
After endoscopy
Causes of portal HTN Omeprazole IV + continuation PO (s re-bleeding)
Pre-hepatic: portal vein thrombosis Keep NBM for 24h clear fluids light diet @ 48h
Hepatic: cirrhosis (80% in UK), schisto (commonest Daily bloods: FBC, U+E, LFT, clotting
worldwide), sarcoidosis. H. pylori testing and eradication
Post-hepatic: Budd-Chiari, RHF, constrict pericarditis Stop NSAIDs, steroids et.c.
Bleed Prevention
O
1 : -B, repeat endoscopic banding Indications for Surgery
2O: -B, repeat banding, TIPSS Re-bleeding
Bleeding despite transfusing 6u
Transjuglar Intrahepatic Porto-Systemic Shunt (TIPSS)
Uncontrollable bleeding at endoscopy
IR creates artificial channel between hepatic vein and
Initial Rockall score 3, or final >6.
portal vein portal pressure.
Open stomach, find bleeder and underrun vessel.
Colapinto needle creates tract through liver
parenchyma which is expand using a balloon and
maintained by placement of a stent. NB. Avoid 0.9% NS in uncompensated liver disease (worsens
Used prophylactically or acutely if endoscopic therapy ascites). Use blood or albumin for resus and 5% dex for
fails to control variceal bleeding. maintenance.
Acute Renal Failure
Common Causes
Pre-renal: shock (e.g. sepsis, hypovolaemia), HRS Resuscitate and Assess Fluid Status
Renal: ATN, TIN, GN A: GCS may need airway Mx
Post-renal: Stone, neoplasm, catheter B: pulmonary oedema sit up, high flow O2
C: Assess fluid status:
CV Tissues End-organ
Presentation Postural BP CRT Mental state
Usually presents in the context of critical illness JVP Cold / warm hands Urine output
Uraemia HR Skin turgor
Hyperkalaemia Mucus membranes
Acidosis
Oedema and BP
Rx Life-Threatening Complications
Ix Hyperkalaemia
Bloods: FBC, U+E, LFT, glucose, clotting, Ca, ESR Pulmonary oedema
ABG: hypoxia (oedema), acidosis, K+ Consider need for rapid dialysis
Urine: dip, MCS, chemistry (U+E, CRP, osmolality,
BJP) Rx Shock or Dehydration
ECG: hyperkalaemia Fluid challenge 250-500ml over 30min
CXR: pulmonary oedema Repeat as necessary: aim for CVP of 5-10cm
Renal US: Renal size, hydronephrosis Once replete, continue @ 20ml+UO/h
Hyperkalaemia
ECG Features (in order) Monitor
Peaked T waves Cardiac monitor
Flattened P waves Urinary catheter
PR interval Consider CVP
Widened QRS Start fluid balance chart
Sine-wave pattern VF
Mx
10ml 10% calcium gluconate
50ml 50% glucose + 10u insulin (Actrapid) Look for Evidence of Post-Renal Causes
Salbutamol 5mg nebulizer Palpable tender bladder
Calcium resonium 15g PO or 30g PR Enlarged prostate
Haemofiltration (usually needed if anuric) Catheter in situ
Complete anuria
Pulmonary Oedema
Sit up and give high-flow O2
Morphine 2.5mg IV ( metoclopramide 10mg IV) Hx and Ix
Hx: Evidence of Acute vs. Chronic RF
Frusemide 120-250mg IV over 1h
Duration of symptoms
Co-morbidities
If no response consider:
CPAP Previous blood results
Haemofiltration / haemodialysis venesection
Ix
Bloods, ABG
Urine dip + MCS + chem
Indications for Acute Dialysis (AEIOU)
1. Persistent hyperkalaemia (>7mM) ECG
2. Refractory pulmonary oedema CXR and Renal US
3. Symptomatic uraemia: encephalopathy, pericarditis
5. Poisoning (e.g. aspirin)
Rx Sepsis
Blood cultures and empirical Abx
Further Mx
Call urologists if obstructed despite catheter
Care with nephrotoxic drugs: e.g. gentamicin

Poisoning: Recognition and Management
Drug Features Mx
Benzodiazepines GCS Flumazenil
Respiratory depression
-Blockers Severe bradycardia or hypotension Atropine
Cyanide Inhibits the cytochrome system Dicobalt edentate
Almond smell
Phase 1: Anxiety confusion
Phase 2: / pulse
Phase 3: Fits, coma
Carbon monoxide Headache, dizziness, nausea Hyperbaric O2
Hypoxaemia (SpO2 may be normal)
Metabolic acidosis
Digoxin GCS Anti-digoxin antibodies
Yellow-green visual halos
Arrhythmias
Ethanol GCS
Respiratory depression
Ethylene glycol AG metabolic acidosis with OG Ethanol
Intoxication with no visual disturbance Haemodialysis
Found in antifreeze
Heparin Bleeding Protamine
Iron Nausea, vomiting, abdo pain Desferrioxamine
Lithium n/v Saline
Ataxia, coarse tremor
Confusion
Polyuria and renal failure
Methanol AG metabolic acidosis with OG Ethanol
Intoxication with visual disturbance Haemodialysis
Opiates Respiratory depression Naloxone
GCS
Pin-point pupils
Organophosphates SLUDGEM Atropine + Pralidoxime
e.g. malathion
Tricyclics QTc Torsade de pointes Activated charcoal
Metabolic acidosis NaHCO3 IV
Anticholinergic effects
Warfarin Major bleed Vit K IV
Prothrombin complex or (FFP)
Aspirin Paracetamol
Effects Effects
Respiratory stimulant respiratory alkalosis Normal metabolism overloaded and paracetamol
Uncouples oxidative phosphorylation met acidosis converted to highly toxic NAPQI by CyP450.
NAPQI can be detoxified by glutathione conjugation
Presentation Overwhelmed in OD
Vomiting and dehydration
Hyperventilation Presentation
Tinnitus, vertigo Vomiting, RUQ pain
Hyper- or hypo-glycaemia Jaundice and encephalopathy liver failure
Respiratory alkalosis initially then lactic acidosis Cerebral oedema ICP
Mixed picture usually HR, decerebrate posture, poor pupil responses
Mx Mx
Activated charcoal if <1h since ingestion Activated charcoal if <1h since ingestion
Bloods Bloods
Paracetamol and salicylate levels Paracetamol level 4h post ingestion
Glucose, U+E, LFTs, INR, ABG Glucose, U+E, LFTs, INR, ABG
Alkalinise urine: NaHCO3 KCl NAC: if levels above treatment line on graph
Haemodialysis may be needed

Diabetic Ketoacidosis
Pathogenesis Management
Ketogenesis
insulin stress hormones and glucagon Fluids
glucose utilisation + fat -oxidation 0.9% NS infusion via large bore cannula
fatty acids ATP + generation of ketone bodies. SBP<90 1L stat + more until SBP >90
SBP>90 1L over 1h
Dehydration Then: 1L over next 2h, 1L/2h, 1L/4h, 1L/4h, 1L/6h
insulin glucose utilisation + gluconeogenesis Add 10% dextrose 1L/8h when glucose <14mM
severe hyperglycaemia
osmotic diuresis dehydration Start Potassium Replacement in 2nd Bag of Fluids
Also, ketones vomiting >5.5mM Nil
3.5-5.5mM 40mM/L
Acidosis <3.5mM consult senior for review
Dehydration renal perfusion
Hyperkalaemia
Insulin Infusion
Precipitants 0.1u/kg/h Actrapid (6u if no wt., max 15u)
Infection / stress stopping insulin
New T1DM
Presentation Assessment
Abdo pain + vomiting Hx + full examination
Gradual drowsiness Investigations: capillary, urine, blood, imaging
Sighing Kussmaul hyperventilation
Dehydration
Ketotic breath Additional Measures
Urinary catheter (aim: 0.5ml/kg/hr)
Dx NGT if vomiting or GCS
Acidosis (AG): pH <7.3 ( HCO3 <15mM) Thromboprophylaxis c LMWH
Hyperglycaemia: 11.1mM (or known DM) Refer to Specialist Diabetes Team
Ketonaemia: 3mM (2+ on dipstix) Find and treat precipitating factors
Ix
Urine: ketones and glucose, MCS Monitoring
Cap glucose and ketones Hrly capillary glucose and ketones
VBG: acidosis + K VBG @ 60min, 2h and then 2hrly
Bloods: U+E, FBC, glucose, cultures Plasma electrolytes 4hrly
CXR: evidence of infection
Aims
Subtleties ketones by 0.5mM/h or HCO3 by 3mM/h
Hyponatraemia is the norm plasma glucose by 3mM/h
Osmolar compensation for hyperglycaemia Maintain K in normal range
/ Na indicates severe dehydration Avoid hypoglycaemia
Avoid rapid in insulin once glucose normalised
Glucose decreases faster than ketones and
insulin is necessary to get rid of them.
Amylase is often (up to 10x) Resolution
Excretion of ketones loss of potential bicarbonate Ketones <0.3mM + venous pH>7.3 (HCO3 >18mM)
hyperchloraemic metabolic acidosis after Rx Transfer to sliding scale if not eating
Transfer to SC insulin when eating and drinking
Complications
Cerebral oedema: excess fluid administration
Commonest cause of mortality Transfer to SC Insulin
Aspiration pneumonia When biochemically resolved and eating
Hypokalaemia Start long-acting insulin the night before
Hypophosphataemia resp and skeletal muscle Give short-acting insulin before breakfast
weakness Stop IVI 30min after short acting
Thromboembolism
Mx: in HDU
Gastric aspiration Pt. Education
Rehydrate ID precipitating factors and provide action plan
Insulin infusion Provision of ketone meter c education on use.
Potassium replacement
Hyperosmolar Non-Ketotic Coma Hypoglycaemia
The Patient Symptoms
Usually T2DM, often new presentation
Usually older Autonomic Neuroglycopenic
Long hx (e.g. 1wk) Sweating Confusion
Anxiety Drowsiness
Metabolic Derangement Hunger Seizures
Marked dehydration and glucose >35mM Tremor Coma
No acidosis (no ketogenesis) Palpitations Personality change
Osmolality >340mosmol/kg
Complications Cause
Occlusive events are common: DVT, stroke Usually Exogenous: insulin, gliclazide
Give LMWH Pituitary insufficiency
Liver failure
Mx Addisons
Rehydrate c 0.9% NS over 48h Insulinomas
May need ~9L
Wait 1h before starting insulin
It may not be needed Mx
Start low to avoid rapid changes in osmolality
E.g. 1-3u/hr Alert and Orientated: Oral Carb
Look for precipitant Rapid acting: lucozade
MI Long acting: toast, sandwich
Infection
Bowel infarct Drowsy / confused but swallow intact: Buccal Carb
LMWH Hypostop / Glucogel
Consider IV access
Unconscious or Concerned re Swallow: IV dextrose

50ml 50% or 100ml 20% glucose
Deteriorating / refractory / insulin-induced / no access

1mg glucagon IM/SC
Wont work in drunks + short duration of effect (20min)
Insulin release may rebound hypoglycaemia

Thyroid Storm Myxoedema Coma
temp Looks hypothyroid
Agitation, confusion, coma Hypothermia
Tachycardia, AF Hypoglycaemia
Acute abdomen Heart failure: bradycardia and BP
Heart failure Coma and seizures
Precipitants Precipitants
Recent thyroid surgery or radio-iodine Radioiodine
Infection Thyroidectomy
MI Pituitary surgery
Trauma Infection, trauma, MI, stroke
Mx Mx
1. Fluid resuscitation + NGT Bloods: TFTs, FBC, U+E, glucose, cortisol
2. Bloods: TFTs + cultures if infection suspected Correct any hypoglycaemia
3. Propranolol PO/IV T3/T4 IV slowly (may ppt. myocardial ischaemia)
4. Digoxin may be needed Hydrocortisone 100mg IV
5. Carbimazole then Lugols Iodine 4h later to inhibit Rx hypothermia and heart failure
thyroid
6. Hydrocortisone
7. Rx cause

Addisonian Crisis Hypertensive Crisis
Presentation Cause
Shocked: HR, postural drop, oliguria, confused Phaeochromocytoma
Hypoglycaemia
Usually known Addisonian or chronic steroid user Presentation
Pallor
Precipitants Pulsating headache
Infection Feeling of impending doom
Trauma BP
Surgery ST and cardiogenic shock
Stopping long-term steroids
Precipitants
Mx Stress
Bloods: cortisol, ACTH, U+E Abdominal palpation
Check CBG: glucose may be needed General anaesthetic
Hydrocortisone 100mg IV 6hrly Parturition
IV crystalloid Contrast media
Septic screen
Treat underlying cause Rx
Phentolamine 2-5mg IV (-blocker) or labetalol 50mg IV
Repeat to safe BP (e.g. 110 diastolic)
Phenoxybenzamine 10mg/d PO when BP controlled
May now give -B to control tachycardia / arrhythmias
Elective surgery after 4-6wks to allow full -blockade
and volume expansion
NB. Never give -B alone first

Burns
Risk Factors Mx
Age: children and elderly Based on ATLS principals
Co-morbidities: epilepsy, CVA, dementia, mental illness Specific concerns
c burns
Occupation Secure airway
Manage fluid loss
Classification Prevent infection
Superficial Airway
Erythema Examine for respiratory burns
Painful Soot in oral or nasal cavity
E.g. sunburn Burnt nasal hairs
Hoarse voice, stridor
Partial Thickness Flexible laryngoscopy can be helpful
Heal w/i 2-3wks if not complicated Consider early intubation + dexamethasone ( inflam)
Superficial
No loss of dermis Breathing
Painful 100% O2
Blisters Exclude constricting burns
Deep Signs of CO poisoning
Loss of dermis but adnexae remain Headache
Healing from adnexae: e.g. follicles n/v
V. painful Confusion
Cherry red appearance
Full Thickness ABG
Complete loss of dermis COHb level
Charred, waxy, white, skin SpO2 unreliable if CO poisoning
Anaesthetic
Heal from the edges scar Circulation
Fluid losses may be huge
2x large-bore cannulae in each ACF
Bloods: FBC, U+E, G+S/XM
Complications
Start 2L warmed Hartmanns immediately
Early
Parkland Formula to guide replacement in 1st 24hrs
Infection: loss of barrier function, necrotic tissue, SIRS,
4 x wt. (kg) x % burn = mL of Hartmanns in 24h
hospital
Replace fluid from time of burn
Hypovolaemia: loss of fluid in skin + cap permeability
Give half in 1st 8h
Metabolic disturbance: K, myoglobin, Hb AKI
Best guide is UO: 30-50mL/h
Compartment syndrome: circumferential burns
Peptic ulcers: Curlings ulcers Muir and Barclay Formula to guide fluid replacement
Pulmonary: CO poisoning, ARDS (wt. x % burn)/2 = mL of Colloid per unit time
Time units: 4, 4, 4, 6, 6, 12 = 36hrs total
Intermediate
May need to use blood
VTE
Pressure sores Burn Treatments
Analgesia: morphine
Late
Dress partial thickness burns
Scarring
Biological: e.g. cadaveric skin
Contractures Synthetic
Psychological problems Cream: e.g. Flamazine (silver sulfadiazine) +
sterile film.
Full thickness burns
Assessment Tangential excision debridement
Split-thickness skin grafts
Wallace rule of 9s: % BSA burnt Circumferential burns may require escharotomy to
Head and neck: 9% prevent compartment syndrome.
Arms: 9% each Anti-tetanus toxoid (o.5ml ATT)
Torso: 18% front and back Consider prophylactic Abx: esp. anti-pseudommonal
Legs: 18% each
Perineum: 1%
(Palm: 1%)
NB. may also use Lund and Browder charts

Hypothermia
Definition Ix
Core (rectal) temperature <35 CO Rectal / ear temperature
FBC, U+E, glucose
TFTs, blood gas
Pathophysiology ECG
Body heat is lost via 4 mechanisms J waves: between QRS and T wave
Arrhythmias
1. Radiation: 60%
Infra-red emissions Mx
Cardiac monitor
2. Conduction: 15% Warm IVI 0.9% NS
Direct contact Urinary catheter
1O means in cold water immersion Consider Abx for prevention of pneumonia
Routine if temp <32 and >65yrs
3. Convection: 15%
Removes warmed air from around the body Slowly Rewarm
d in windy environments Reheating too quickly peripheral vasodilatation and
shock.
O
4. Evaporation: 10% Aim for 0.5 C /hr
Removal of warmed water Passive external: blankets, warm drinks
in dry, windy environments Active external: warm water or warmed air
Active internal: mediastinal lavage and CPB
Severe hypothermia only
Aetiological Classification
Primary: environmental exposure
Secondary: change in temperature set-point Complications
E.g.: age-related, hypothyroidism, autonomic Arrhythmias
neuropathy Pneumonia
Coagulopathy
Presentation Acute renal failure
Mild: 32.2 35OC

Shivering
Tachycardia
Vasoconstriction
Apathy
Moderate: 28 32.2OC
Dysrhythmia, bradycardia, hypotension
J waves
reflexes, dilated pupils, GCS
Severe: <28OC
VT VF Cardiogenic shock
Apnoea
Non-reactive pupils
Coagulopathy
Oliguria
Pulmonary oedema

2010 Resuscitation
Guidelines
Resuscitation Council (UK)
Adult Advanced Life Support
Unresponsive?
Not breathing or
only occasional gasps
Call
resuscitation team
CPR 30:2
Attach defibrillator / monitor
Minimise interruptions
Assess
rhythm
Shockable Non-Shockable
(VF / Pulseless VT) (PEA / Asystole)
1 Shock Return of
150J Biphasic
spontaneous
360J Monophasic circulation
Immediately resume Immediate post cardiac Immediately resume

CPR for 2 min arrest treatment CPR for 2 min
Use ABCDE approach
Adrenaline 1mg Controlled oxygenation and Adrenaline 1mg as soon
+ amiodarone 300mg ventilation as IV access obtained
after 3rd shock 12-lead ECG
Treat precipitating cause
Repeat adrenaline every Repeat adrenaline every
Temperature control /
other cycle therapeutic hypothermia other cycle
During CPR Reversible Causes

Ensure high-quality CPR: 100/min, 4cm deep Hypoxia
Plan actions before interrupting CPR Hypovolaemia
Give oxygen Hypo- / hyperkalaemia / metabolic
Consider advanced airway and capnography Hypothermia
Continuous chest compressions when advanced
airway in place Thrombosis - coronary or pulmonary
Vascular access (intravenous, intraosseous) Tamponade - cardiac
Give adrenaline every 3-5 min Toxins
Correct reversible causes Tension pneumothorax

2010 Resuscitation
Guidelines
Assess using the ABCDE approach

Adult tachycardia (with pulse) Give oxygen if appropriate and obtain IV access
algorithm Monitor ECG, BP, SpO2 , record 12-lead ECG
Identify and treat reversible causes (e.g. electrolyte abnormalities)
Adverse features?
Synchronised DC Shock Yes / Unstable Shock
Up to 3 attempts Syncope
Myocardial ischaemia
Heart failure
Amiodarone 300 mg IV over 10-20 min
and repeat shock; followed by: No / Stable
Amiodarone 900 mg over 24 h
Broad Is QRS narrow (< 0.12 s)? Narrow
Irregular Broad QRS Regular Regular Narrow QRS Irregular

Is rhythm regular? Is rhythm regular?
Use vagal manoeuvres Irregular Narrow Complex

Adenosine 6 mg rapid IV bolus; Tachycardia
if unsuccessful give 12 mg;
Probable atrial fibrillation
!
Seek expert help if unsuccessful give further 12 mg.
Monitor ECG continuously Control rate with:
-Blocker or diltiazem
Consider digoxin or amiodarone
Sinus rhythm restored? if evidence of heart failure
Possibilities include: If ventricular tachycardia

Yes No
AF with bundle branch block (or uncertain rhythm):
Amiodarone 300 mg IV
!
treat as for narrow complex Seek expert help
over 20-60 min;
Pre-excited AF then 900 mg over 24 h Probable re-entry paroxysmal SVT:
consider amiodarone Record 12-lead ECG in sinus
Polymorphic VT If previously confirmed rhythm
(e.g. torsade de pointes - SVT with bundle branch block: If recurs, give adenosine again &
give magnesium 2 g over 10 min) Give adenosine as for regular consider choice of anti-arrhythmic Possible atrial flutter
narrow complex tachycardia prophylaxis Control rate (e.g. -Blocker)

2010 Resuscitation
Guidelines
Adult bradycardia algorithm
Assess using the ABCDE approach

Give oxygen if appropriate and obtain IV access
Monitor ECG, BP, SpO2, record 12-lead ECG
Identify and treat reversible causes
(e.g. electrolyte abnormalities)
Adverse features?
YES Shock NO
Syncope
Myocardial ischaemia
Heart failure
Atropine
500 mcg IV
Satisfactory YES
response?
NO
Interim measures: Risk of asystole?

Atropine 500 mcg IV Recent asystole
repeat to maximum of 3 mg Mobitz II AV block
YES
Isoprenaline 5 mcg min-1 IV Complete heart block
Adrenaline 2-10 mcg min-1 IV with broad QRS
Alternative drugs * Ventricular pause > 3 s
OR
Transcutaneous pacing NO
Seek expert help ! Observe

Arrange transvenous pacing
* Alternatives include:
Aminophylline
Dopamine
Glucagon (if beta-blocker or calcium channel blocker overdose)
Glycopyrrolate can be used instead of atropine

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What are some reversible causes of cardiac arrest?

What are some reversible causes of cardiac arrest?

Medicine

Alasdair Scott, 2012 1

View Leads Vessel

Alasdair Scott, 2012 2

2. Rhythm 7. QTc (380-420ms)

Abnormality Features ECG

2nd Degree Heart Block Progressive lengthening of

One non-conducted P wave

Next conducted beat has

Often wide QRS

3rd Degree Heart Block P waves and QRS @

Abnormally shaped QRS

Abnormality Features ECG Aetiology

Left BBB WiLLiaM Fibrosis

Bifascicular Block RBBB + LAD RBBB + Left ant. hemiblock

Alasdair Scott, 2012 4

May be SAN failure no P

Extrasystoles: appear early (before anticipated beat)

Nodal Extrasystole P wave buried in QRS or

Alasdair Scott, 2012 5

AVRT P waves usually visible

QRS may be narrow or wide

Accessory conduction bundle

Normal QRS complexes.

Rate > 150bpm

Atrial Flutter Saw-toothed baseline as

AVN cant conduct > 200bpm

Irregularly irregular QRS

Alasdair Scott, 2012 6

Regular, wide QRS

Ventricular tachycardia vs. SVT with bundle branch block

VT more likely if:

Alasdair Scott, 2012 7

P mitrale Broad, bifid P wave LAH

Normal QRS width

May be T wave inversion in

May be T wave inversion in

Alasdair Scott, 2012 8

Slurred upstroke of QRS called a

Can establish re-entrant circuit

AF + WPW irregularly irregular

Digoxin Reverse tick

PE SI QIII TIII (rare)

Right vent strain

Fig shows serial in K+

Alasdair Scott, 2012 9

Causes: DIVISIONS Classification

Sick sinus syndrome 3. Pacing: External

Septal defect: primum ASD

Alasdair Scott, 2012 10

Definition: Rate >100bmp, QRS width < 120ms

Regular rhythm? NO Treat as AF

Alasdair Scott, 2012 11

Correct Electrolyte Problems Amiodarone:

Alasdair Scott, 2012 12