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    Renal Lecture 1a

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    tyhbbhh
    The patient has nephrogenic diabetes insipidus, where the kidney does not respond to ADH normally and cannot concentrate the urine. Central diabetes insipidus would show an improvement with ADH administration.

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    Renal Lecture 1a

    Uploaded by

    tyhbbhh
    17 views34 pages
    The patient has nephrogenic diabetes insipidus, where the kidney does not respond to ADH normally and cannot concentrate the urine. Central diabetes insipidus would show an improvement with ADH administration.

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    Renal lecture 1a

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    The patient has nephrogenic diabetes insipidus, where the kidney does not respond to ADH normally and cannot concentrate the urine. Central diabetes insipidus would show an improvement with ADH administration.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    17 views34 pages

    Renal Lecture 1a

    Uploaded by

    tyhbbhh
    The patient has nephrogenic diabetes insipidus, where the kidney does not respond to ADH normally and cannot concentrate the urine. Central diabetes insipidus would show an improvement with ADH administration.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 34

    Renal System Biochemistry

    and Endocrinology
    Aims
    Role of kidney in electrolytes and fluids
    Hormones produced by and acting on kidney
    • ADH
    • Renin Angiotensin System
    • Vitamin D
    • Erythropoietin
    • PTH/Calcium
    Renal System Biochemistry
    and Endocrinology
    Clinical Biochemistry
    • Renal system is very important
    • “Fluids and Electrolytes”
    • Control osmolality
    • Amount of sodium in plasma - Osmolality = 2 x [Na+]
    • Increase osmolality by increasing sodium or by
    decreasing fluid

    COVER IN YEAR 3
    Concentration
    A measure of how much solute (salt) is
    in a given volume of solvent

    increasing Concentration decreasing


    solvent decreased by : solute

    decreasing Concentration increasing


    solvent increased by : solute
    Osmolality
    Osmolality reference range

    = 280-290 mOsm/Kg

    = 2 x [Na+] + [urea] + [glucose]


    Osmolality
    • Osmolality reference range = 280-290 mOsm/Kg
    • Sodium reference range = 132-144 mmol/L
    • Urea reference range = 2.5-6.6 mmol/L
    • Glucose reference range = 3.6-5.8 mmol/L

    = 2 x [Na+] + [urea] + [glucose]

    thus osmolality = 2 x [Na+] (normally)


    Osmolality
    Labs
    • measure osmolality (serum and urine)
    • measure Na+ - ion electrodes
    • values may not agree
    Kidney Function
    The kidney is a complex organ with multiple
    biochemical functions.

    Excretion
    • nitrogenous end products – urea, creatinine, uric acid
    • inorganic by-products – sulphate, phosphate

    Regulation
    • water
    • electrolytes – Na+, K+, Cl-
    • acid-base balance – HCO3-
    Filtration System
    Nephrons
    1,000,000 per kidney
    Nephron
    Collecting
    duct, water
    Blood
    recovered
    Branch of filtered
    renal
    artery

    Branch
    of renal
    vein

    Salts,glucose,
    amino acids
    recovered Urine, waste
    products, xs water,
    salts, glucose,
    xenobiotics, eg drug
    metabolites
    Nephron
    proximal
    convoluted distal
    tubule convoluted
    tubule
    glomerulus

    collecting
    duct

    Aldosterone
    ADH
    Sodium Water
    Reabsorption Reabsorption
    loop of Henle
    Endocrine Functions
    • Interaction with ADH (AVP) – water balance
    • Renin synthesis – renin-angiotensin system (RAS)
    • Interaction with aldosterone – sodium balance

    • Erythropoietin synthesis
    • 1,25-dihydroxy vitamin D synthesis
    • Interaction with PTH in calcium and phosphate regulation
    Anti-Diuretic Hormone
    • “Diuresis” – flow of urine from kidney
    • “Anti” – opposes this
    • Also known as Arginine Vasopressin (AVP)
    • Released from posterior pituitary

    Phe
    Tyr
    Gln
    Cys

    Cys Asp

    Pro

    Arg
    Gly
    ADH released in
    response to increased
    AADH
    osmolality

    TSH, LH/FSH, GH, etc


    Year 3
    Anti-diuretic
    Hormone (ADH)
    -“turns of tap”

    Diabetes Insipidus
    - lack of function in posterior
    pituitary
    - or lack of ADH response in
    kidney
    - reduced ADH production/action
    - up to 25L of urine produced
    ADH Secretion

    Stimulated by: Inhibited by:


    ­ osmolality ¯ osmolality
    ¯ volume >10% ­ volume
    Increasing ADH

    1. Increased Blood Volume


    - reduced osmolality
    - less sodium per unit volume

    2. Concentrated Urine
    - increased osmolality
    - more ions per unit volume
    ADH Action

    • opens water pores in


    collecting ducts
    • water is recovered
    from urine
    ADH & Osmolality

    Plasma ADH concentration

    Thirst

    270 280 290 300 310


    Plasma osmolality mOsmol/kg
    Aldosterone Action
    Aldosterone

    Recovers Na+
    in exchange for K+
    or H+ if [K+] is low
    Renin-Angiotensin Pathway
    • Renin
    – Made by kidney
    • Angiotensinogen
    – Made by liver
    • Angiotensin I (AI)
    – Converted from angiotensinogen by renin
    • Angiontensin II (AII)
    – Converted from AI in lungs by ACE
    – (angiotensin converting enzyme)
    Renin-Angiotensin System
    Low blood pressure/reduced Na+

    Angiotensinogen
    renin
    Angiotensin I Adrenal cortex

    ACE
    Aldosterone
    Angiotensin II

    Renal Na+
    fluid retention
    J cells
    • release renin
    • in response to decreased blood pressure
    Na+ é Na+ ê

    NB. Note that K+ and Na+ are counter balanced


    Angiotensin II

    • Constricts blood vessels, increasing BP

    • Stimulates adrenals to release aldosterone

    • Stimulates pituitary to release ADH

    • Stimulates thirst centres in brain


    Erythropoietin
    A hormone made in the kidney

    Red blood
    cell
    synthesis
    Release to circulation
    Vitamin D Metabolism
    7-dehydrocholesterol
    in skin

    cholecaciferol - vit D3
    in liver
    25-hydroxycholecalciferol

    in kidney

    1,25-dihydroxycholecalciferol
    Summary

    1. Kidney controls serum water and sodium


    through
    2. ADH and aldosterone
    3. Kidney has other endocrine functions
    Case Study 1

    Young man brought into A &E after being involved


    in motor cycle accident in which he suffered a
    head injury.

    Serum analysis of sodium = 155 mOsm/kg


    Reference value 135-145 mOsm/kg

    What caused this hypernatraemia ?


    What would osmolality of urine be ?
    Case Study 2

    A young lady has hypoadrenalism (reduced output


    of hormones by adrenal medulla) and has not
    taken medication.

    Serum analysis of sodium = 105 mOsm/kg


    Reference value 135-145 mOsm/kg

    Serum analysis of potassium = 10 mOsm/kg


    Reference value 3.6-5 mOsm/kg

    What caused this severe hyponatraemia and


    hyperkalaemia ?
    Case Study 3
    45 year old male admitted to A&E late at night, comatose.
    No history, exam difficult. Strong smell of alcohol.

    sodium 137 mmol/l 135-145 mmol/l


    potassium 3.3 mmol/l 3.5-5.0 mmol/l
    urea 4.7 mmol/l 3.5-6.5 mmol/l
    glucose 4.2 mmol/l 2.8-6.0mmol/l
    osmolality 465mmol/kg 280-295 mmol/kg

    What is the calculated osmolality?


    Why the difference?
    Case Study 4
    Middle aged male. Signifcant polyuria (>10L). Selected
    analysis of urine and blood given below.

    Analyte Measured Reference Range


    Sodium (blood) 137 mmol/l 135-145 mmol/l
    Osmolality (blood) 300 mmol/kg 280-295 mmol/kg
    Osmolality (urine) 100 mmol/kg

    The patient was given was ADH but this did not reduce
    hypernatremia or concentrate urine.

    What is wrong with patient ?


    Nephrogenic v Central
    • polyuria, dilute urine, hypernatreamia
    • following administration of ADH

    Serum
    Urine Urine
    Osmolality “Fixed ?”
    Osmolarity Production

    Central YES

    Nephrogenic unchanged unchanged unchanged NO

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