Handout

Disease of the blood

Physiology of blood
Definition of blood
Blood is a specialised connective tissue in which there is liquid intercellular substances(plasma)
and formed elements ( RBC, WBC and platelets) substance in the plasma which circulated in
closed system of blood vessels.
It is red, thick and slightly alkaline.

Blood is a body fluid circulating through the heart, arteries, capillaries and veins
Composition of - Plasma (fluid) - 55%, 92% water, 7% proteins, 1% others such as fats,
carbohydrates.
Cellular components - 45% : RBC (erythrocytes)WBCs (leucocytes) and Platelets (thrombocytes)

Function of Blood
1. Transport of respiratory gasses.
2. Transport of nutrients
3. Regulation of body temperature
4. Maintain of acid base balance
5. Regulate blood pressure and electrolyte
6. Prevent haemorrage

RBC -biconcave disc, 5 mil/mm , life span 120 days

-mainly contains haemoglobin responsible for oxygen transport, 14 -15g/100 ml of blood.
Haemoglobin : It is a conjugated protein. It is the red pigment inside the red blood cell.

It is a chromoprotein consisting of two parts –i. Globin and ii Haem.

Hb( gm/dl) : Male 11.5 –16.5 gm/dl and Female: 13-15 gm/dl

WBC - ( thous/mm3); 4-11

Granulocytes:
-Neutrophils
-Basophils
-Eosinophils
Mononuclear leucocytes:
-Monocytes
-lymphocytes
Platelets – 150,000 – 450,000/mm
Primary function platelets is to control bleeding through haemostasis.

Major manifestations of Blood disease;

1. Blood disorder characterized by disruption of :
-Haemotologic system( anaemia)
-Immune system ( thrombocytopenic purpura)
-Bleeding (coagulation) disorder
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2. Patient presents with complaints
-fatigue
-frequent infections
-swollen glands ( lymphadenopathy)
-bleeding tendencies
-Splenomagaly
In Anaemia
Pallor of conjunctiva, nail bed, lips and mucous membrane. Smooth shining dry tongue, sore,
dyspnoea and tachycardia.

Bleeding disorder
Bleeding, petechiae, black stools, red urine, decreased BP, altered consciousness
Infection : Fever, tachycardia, chest infections and oral lesions
History: Symptoms, possible sources of blood loss
Others history:
 Ask about drugs, medications
 Past medical/surgical history
 Occupation, family history
 Dietary habits
System examination
Skin - Mucous membrane -bruises, infection, bleeding, pallor
CNS - fatigue, weakness , dizziness
Respiratory . -shortness of breath on exertion
CVS -chest pain, palpitations
GIT -bleeding gums, abdominal pain, black stools
Urinary -blood in urine
Investigations
1. Complete blood count (CBC) and peripheral blood film
2. Blood film;
i. Platelets
ii. RBC
iii. RBC ( MCV, MCH, MCHC)
iv. WBC
v. Reticulocyte count
3. Bone marrow aspiration
4. Lymph node biopsy

Disorders of erythrocytes( RBC);

Anaemia
Definition: Lack of sufficient circulating haemoglobin to deliver oxygen to the tissues.
or

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Anemia may be defined as a state in which the blood hemoglobin level is below the
normal range for the patient’s age and sex.
The causes of iron deficiency anemia are:
 Excessive bleeding like sudden accidents. In chronic case like nose bleed, ulcer in
stomach
 Poor diet
 Decrease of RBC
 Chronic diseases.
 Heavy menstruation
 Iron deficiency
 Lack of folic acid and vitamin B12 in the body
 Decrease marrow production
Signs and symptoms
 Weakness and tiredness
 Trachycardia
 Oedema in severe case
 Palpitation
 Congestive cardiac failure
 Pale skin-lips and tongue

Investigations: Blood for CBC and Underlying causes.

Treatment for anaemia

 Different treatment options
 Green vegetables and fruits
 Iron supplement
 Blood transmissions
 The drugs most commonly used are:
 Ferrous sulphate and folic acid (FS/FA)
 Iron dextran injection
 Folic acid
 Blood transfusion
Treatment of iron overload
 Iron therapy forbidden
 Desferriaxamine (iron chelating agent) 1-5-29 – S/C infusion over 8-12 hour on
five to 6 heights/week in a dosage of 50mg/kg weight
 Tab. Ascorbic acid 200 mg daily

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Classification of anaemia
1. Iron Deficiency Anaemia
2. Megaloblastic Anaemia-
a) Pernicious (Vit B 12 deficiency)
b) b) Folic acid deficiency

3. Aplastic Anaemia
4. Hemolytic anemia
5. Aplastic anaemia
6. Pernicious anemia
7. Thalassemia
Patho physiological classification of anaemia
a. Haemorrhagic/blood loss anaemia
 Acute blood loss
 Chr. Blood loss
b. Impaired RBC production
 Nutritional deficiency anemia
 Aplastic anaemia (marrow infiltration) due to leukemia
 Chr. Renal failure
 Anemia of Chr. Disease

c. Haemolytic anemia

Morphological classification of anaemia (microscopic examination);

a. Normocytic normochromic anaemia; ( Normal size RBC and normal colour)
i. Acute blood loss
ii. Aplastic anaemia
iii. Chronic renal f ailure
b. Microcytic hypochromic anemia ; ( RBC size small and abnormal Hb in RBC)
i. Iron deficiency anemia
ii. Thalassaemia
c. Macrocytic anaemia : ( bigger size RBC )
i. Vitamin B 12 deficiency
ii. Folate deficiency

*For remember
Disorder of RBC Disorder of WBC Bleeding disorders Disorder of the
lymphoid tissue
i. Anemia Leukaemia Thrombocytopenia
ii. Iron deficiency anaemia Lymphoma
iii. Megalo blastic anaemia
iv. Aplastic anaemia

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i. Iron deficiency anaemia; ( Microcytic, hypochromic anaemia)
It is a condition in which total body iron content is decreased below a normal level affecting
haemoglobin synthesis.
-haemoglobin is made of - Haeme and Globin
Decreased Hb result in insufficient delivery of oxygen to the tissues

Iron deficiency anaemia is the most common type of anaemia. It is a major health problem in
developing countries.
Classification
13-14 g% Normal
10-12 g% Mild
6-9 g/% Moderate
<6 g/% Severe

Path physiology (causes)

1. Chronic Blood Loss
-G.I bleeding
-Excessive menstrual bleeding
-Repeated pregnancies
-Hookworm infestation
-Malaria
-Injuries
2. Defective Iron metabolism
3. Increased requirements
-during pregnancy
-during periods of rapid growth
4. Insufficient intake
-inadequate diet
-weight loss, malnutrition, loss of appetite
-chronic alcoholism
*Clinical feature of iron deficiency anaemia
1. Physical
-headache, dizziness, tinnitus
-palpitation, breathlessness, tachycardia
-pallor of skin, mucous memb
-smooth, sore tongue, cheilosis
-koilonychia, edema
2. Behavioral
-fatigue, weakness
-pica (craving to unusual substances)
Investigations
1. Complete blood count
2. Determination of source of chronic blood loss
3. Stool for ova/cyst, occult blood

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Treatment for iron deficiency
1. Correction of chronic blood loss
2. Oral or Parental therapy
a) Oral ferrous sulphate ( with Folic acid)-upto 6months after Hb normal
b) Parenteral therapy- when unable to tolerate or non compliant with oral
3. Therapy. Iron Dextran ( Inferon )
4. Promoting Iron Intake; Assess diet for inclusion of foods rich in iron

Complications for iron deficiency anaemia

1. Severe compromise of oxygen carrying capacity of blood may predispose to ischaemic organ
damage e.g. Myocardial Infarction, Cerebro-vascular accident
2. Anaphylaxis to parenteral therapy.

Definition:
ii. Megaloblastic anaemia: The anemia which are characterized by destruction by distinctive
cytologic and functional abnormalities in peripheral blood and bone marrow class due to
impaired DNA synthesis as a result of vitamin B12 or folic acid deficiency or both are known as
Megaloblastic anaemia

iii. Haemolytic anaemia : A haemolytic anemia may be define as an anemia resulting form as
increase in the rate of red blood cell destruction.

iv. Aplastic anaemia: Aplastic anaemia may be define as a disorder characterized by the
occurrence of anaemia, leucopenia and thrombocytopenia, resulting from aplasia of the bone
marrow.
Causes
 Primary: congenital and Idiopathic acquired
 Secondary : drug , chemicals and physical agent and X-ray

Clinical feature for aplastic anaemia

Age incidence: at any age but peak around 30 years. Onset is insidious.
Symptoms
 Features of anaemia : weakness, fatigue, dyspnoea on exertion.
 Sore throat, ulcer of the mouth and pharynax and repeated history of infection.
 Bleeding manifestations; purpura, epistaxis, gum bleeding , haematuria, bleeding form
alimentary tract and intraceanial haemorrhage.
Signs: Anemia, high temperature, tongue or glossitis
Investigations
1. Blood for CBC
2. Peripheral blood film
3. Bone marrow
4. X-ray bone

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Treatment
1. Symptomatic and supportive treatment
2. Prevent infection
Advice
1. Avoid injury
2. Avoid intramuscularly injection
3. Avoid contact with infected person
4. Avoid hospitalization as far as possible
5. Avoid prophylactic antibiotic
Prognosis for aplastic anaemia
1. Only with supportive treatment: 50% mortality
2. After bone marrow transplantation :60% survival
3. After immuno-suppressesant :60% survival

iv. Pernicious anaemia; The fundamental defect in pernicious anaemia is a failure of

secretion of intrinsic factors by the stomach due to permanent atrophy of the gastric
mucosa.
Gastric atrophy is the end result of complex interaction between a severe hyperchromic
anemia marked by a progressive decrease in number and increase in size and hemoglobin
content of the red blood cells and by pallor, weakness, and gastrointestinal and nervous
disturbances and associated with reduced ability to absorb vitamin B12 due to the absence of
intrinsic factor—called also addisonian anemiaeen genetic and autoimmune factors.

Thalassemia:
It is an inherited impairment of hemoglobin production, in which there is partial or
complete failure to synthesis a specific type of globin chains.
Or Thalassemia is a chronic congenital haemolytic anemia in which red blood cells have
abnormal hemoglobin.

Thalassemia is the name of a group of genetic blood disorders. To understand how

thalassemia affects the human body, you must first understand a little about how blood is
made.
Hemoglobin is the oxygen-carrying component of the red blood cells. It consists of two
different proteins, an alpha and a beta.

Types of Thaslassaemia
1. Thalassemia Minor or Thalassemia Trait. Heterozygous state-called B-thalassaemia
minor.
In this condition, the lack of beta protein is not great enough to cause problems in the
normal functioning of the hemoglobin. A person with this condition simply carries the
genetic trait for thalassemia and will usually experience no health problems other than a
possible mild anemia.

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2. Thalassemia Major or Cooley's Anemia. Homozygous state-called B – thalassaemia
major. This is the most severe form of beta thalassemia in which the complete lack of
beta protein in the hemoglobin causes a life-threatening anemia that requires regular
blood transfusions and extensive ongoing medical care. These extensive, lifelong blood
transfusions lead to iron-overload which must be treated with chelation therapy to prevent
early death from organ failure.

Clinical Feature
 Anaemia
 Jaundice: Mild to moderate
 Severe in the first year of life
 Failure to thrive (growth retardation)
 Splenomogaly – early & prominent feature, usually huge
 Hepatomegaly- slower to develop
 Complication due to haemosiderosis (transfusion therapy): Heart failure

Investigations for Thalassemia

 Hemoglobin estimation – markedly reduced
 Bone marrow
 Pheripheral blood film – microcytic hypochromic RBC < target cell Nucleated
RBC, Reticulocyte count increased (> 10%)

Treatment
1. Regular fresh blood transfusion to maintain haemoglobin above 10 g/dl
packed cell transfusion 15 mi/kg every 4-6 weeks, whole blood transfusion
2. Tab folic acid 5 mg daily life long
3. Bone marrow transplantation
4. Spleenectomy

(Blood Transfusions for thalassemia patient): How it works?

The most common treatment for all major forms of thalassemia is red blood cell transfusions.
These transfusions are necessary to provide the patient with a temporary supply of healthy red
blood cells with normal hemoglobin capable of carrying the oxygen that the patient's body needs.

While thalassemia patients were given infrequent transfusions in the past, clinical research led to
a more frequent program of regular blood cell transfusions that has greatly improved the
patients' quality of life. Today, most patients with a major form of thalassemia receive red blood
cell transfusions every two to three weeks, amounting to as much as 52 pints of blood a year.

How to prevent Iron Overload?

Because there is no natural way for the body to eliminate iron, the iron in the transfused blood
cells builds up in a condition known as "iron overload" and becomes toxic to tissues and organs,
particularly the liver and heart. Iron overload typically results in the patient's early death from

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organ failure.

Chelation Therapy ( iron chelating agent )

To help remove excess iron, patients undergo the difficult and painful infusion of a drug,
Desferal. Or Deforocmine injection ( 1.5 – 2 gm) subcutaneous infusion.

A needle is attached to a small battery-operated infusion pump and worn under the skin of the
stomach or legs five to seven times a week for up to twelve hours. Desferal binds iron in a
process called "chelation." Chelated iron is later eliminated, reducing the amount of stored iron.

Disorders of the white cells ( WBC);

Leukemia
It is a malignant proliferation precursors by the bone marrow. It results in the uncontrolled
production of leucocyte (WBC).
Causes
 Chemical substance
 Genetics
 Radiation ( Ionizing ) : X-ray , Radioactive isotopes
Types
1. Acute leukemia
2. Acute Myeloblastic leukemia (AML) is common in adult.
3. Acute lymphoblastic leukemia( ALL) is common in children
Clinical features leukemia
1. Features of anaemia
2. Features of infection : Fever, sore throat, mouth ulcer
3. Bleeding manifestation : Gum bleeding, bleeding form nose
4. Generalized lymphadenopathy and hepato- splenomegaly
5. Other features ; Joint pain, gum hypertrophy
Investigations
1. Blood CBC
2. Bone marrow

Management
1. Chemotherapy
2. Blood transfusion ( fresh blood should be finish with in 4 hours)
3. Bone marrow transplantation
4. Supportive therapy
5. Stem cell transplantation

Coagulation disorders
Hemophilia
It is an inherited abnormality of blood coagulation characterized by tendency of hemorrhage
form a trauma. It is due to deficiency of plasma factors VIII( Antihaemophilic globuin) factor

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and IX ( Christmas disease ) and factors XI. Hemophilia A and B X-liked recessive condition
and occur almost in males.
Or Haemophilia is congenital bleeding disorder caused by genetic lack of at least one
coagulation factors.
Types

 Haemophilia A - factor VIII deficiency, "classic haemophilia" (X-linked

recessive)
 Haemophilia B - factor IX deficiency, "Christmas disease" (X-linked recessive)
 Haemophilia C - factor XI deficiency (Ashkenazi Jews, autosomal recessive)

Genetics function in Haemophilia

Causes: Deficiency of coagulation factors

Clinical manifestation:
Hemophilia is most commonly subcutaneous and intramuscularly. Hematoma and less
commonly bleeding form mucosal surface.
Epistaxis, Haematemesis, Malana , Haemotoma, and Haematuria

Investigations: Blood for CBC and Blood clotting test

Treatment : 1.Prophylaxis
i) These children and their families should be educated early for
the avoidance of trauma.
ii) Intramuscular injections and asprin must be avoided.
iii) Home treatment with self –administration of factors
concentrated can be taught to school –age children and their
parents

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2. Plasma transfusion within 30 minutes
3. Though there is no cure for haemophilia, it can be controlled with regular injections of
the deficient clotting factor, i.e. factor VIII in haemophilia A or factor IX in haemophilia
B.

Diseases due to the heart valves caused : Rheumatic fever

Rheumatic fever is a systemic illness occurs in children or young adults as result of
infection with group A streptococcus.
Clinical Diagnosis for Rheumatic fever:
Rheumatic fever is diagnosed when two or more major criteria; or one major and two
minor criteria plus in each case evidence of preceding streptococcal infections are
present.
Manifestations of Rheumatic fever:
Types:
a) Major criteria :
Arthritis: Joint pain with hot, red, tender and swollen and sever pain in the large joint
Such as Knee, ankle and wrist joint). Arthritis usually subsides with in 3 week.
Carditis (heart problems): Central Chest pain, breathlessness, palpitation and murmur
may present. It is very dangerous as it causes permanent damage to the heart.
Erythema marginatum: (Skin lesions) It starts as transient pink or pale red macula with
fade centre appears and disappears within a period hours.
Erythema nodosum: Subcutaneous nodules (erythema nodosum ) painful red/ blue
raised lumps over the front of the lower legs and the back of the forearms. They are
situated subcutaneously, painless, not attached to the skin and occur on bony prominence
such as knees, elbows, scapulae, vertebrae or tendon.
Sydenham’s chorea: It is neurological manifestation of acute rheumatic fever .
b) Minor criteria :
 Fever with sweating
 Evidence of sore throat
 Blood : Raised ESR
 Previous history of fever or rheumatic fever
 Joint pain

Pathogenesis:
There is a well –defined association between group A streptococcal pharyngitis and
rheumatic fever. After pharyngeal infection with group A streptococci, specific antibody
is produced against cell wall constituents (N- acetyl-glycosamine) of the bacteria.
As heart valve or cardiac tissue glycoprotein shares the same antigenic properties of (N-
acetyl-glycosamine), so the antibody produce against bacterial cell wall cross-react with
heart valve.
Investigations
1. Blood R/E : Leucocytosis : W.B.C count increased and high ESR
2. Anti-streptolysis O antibody (ASO titres) : Rising titre > 200 units ( adult)
and > 300 unit for children.

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3. Chest X-ray: Cardiomegaly (Enlargement of heart).
4. Throat swab culture: Group A beta haemolytic streptococci.
5. ECG and Echocardiography: Cardiac dilatation and valve abnormalities.

Complications
 Heart failure
 Valvular heart diseases
 Percarditis and
 Percardial effusion

Treatment for Rheumatic fever

Symptomatic and supportive treatment
Bed rest
For severe arthritis : Tab Asprin ( 75mg) 100mg/kg/ day or Ibuprofen( 400mg) :5 mg/kg/
does after meals.
For Infection: Antibiotic
Refer the patient as soon as possible
 All new patients – for diagnosis by a doctor
 Heart murmur with developing of cardiac symptoms and signs
 Worsening of clinical signs of heart disease
 Any other newly developing medical condition, fever
Treatment for Rheumatic fever with complication of valvular heart disease treatment
should be start after laboratory confirmatory test (ASO titres and echocardiography):
Injection Benzathine penicillin (24 lakh): Child under 30 kg: 600 000 IU and
children and adult over 30 kg: 1.2 million.
I/M in buttock, on diagnosis, once weekly for 4 weeks ( every 3 weeks recommended in
high risk situation) then monthly for 1 year to 5 years.

Follow up by ECG and Echocardiography, yearly.

Or
According to Weight:
<30kg: 125mg tds for 10 days.
>30 kgs: 250mg tds for 10 days.
OR
Tablet Erythromycin 10mg-20mg/kg QID( Penicillin allergic).

Duration of antibiotic is based on clinical presentation

 Acute RF without with out cardiac involvement: 5 years or until age of 18 years,
which over longer

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 Acute RF with mild or resolved carditis involvement: 10 years or until age of 25
years, which over longer
 Acute RF with severe carditis or cardiac surgery : Life long

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