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Flashcards

Clinical Biochemistry

Kitty Wong Medicine English 169 cards

Cards in this deck (169)

  1. 1What is the pathway of the Hypothalamic - Anterior pituitary axis?1. Hypothalamic neuro secretory cell
    2. Portal system
    3. Anterior pituitary
    4. Secretion of stimulating hormones
    5. Target gland stimulated to make target gland hormone
    6. Feedback to hypothalamus
  2. 2What causes pituitary OVER-production disorders?Secretary pituitary tumour --> autonomous production of stimulating hormones --> Raised target gland hormone.
    Target gland failure --> No feedback --> low target gland hormone, high pituitary stimulating hormones.
  3. 3What causes pituitary UNDER-production disorders?Pituitary Failure --> No stimulating hormones --> Low target gland hormones.
    Overactive target gland --> High target gland hormones --> Feedback inhibition causes low pituitary stimulating hormones.
  4. 4Investigations for anterior pituitary function?1. Basal hormone measurements
    2. Stimulation Testing
    3. Suppression Testing
  5. 5Why are basal hormone measurements a limited ix? (Why is it not very useful?)Because hormones fluctuate during the day. (Diurnal rhythms, pulsatile release etc.)
  6. 6What is used for stimulation testing for: ACTH TSH LH/FSH GHACTH - Hypoglycaemia, CRF
    TSH - TRH
    LH / FSH - LHRH
    GH - Hypoglycaemia
  7. 7What is used for suppression testing for: ACTH GHACTH - Dexamethasone
    GH - Glucose
  8. 8Growth hormone excess: Phenotypic changes?Pre-pubertal: Growth excess
    Adult: Acromegaly
    Coarse facial features, remodelling of bone / nasal pharynx - sleep apnoea, enlarged jaw, spreading of dentition, enlarged hands and feet.
  9. 9Growth hormone excess: Physiological changes?Reduced libido / 2º sex characteristics
    Hypertrophic myopathy - 2º hypertension
    Increased GI polyps / malignancy risk
    Glucose intolerance - DM risk
    Hypercalciuria - Renal colic risk
  10. 10What causes growth hormone deficiency?1.Destructive lesions (tumours, surgery, irradiation, meningitis, head injury)
    2. Psychological
    3. Endocrine disorders - Laron Dwarfism (GH-r defect)
  11. 11What is the diagnostic criteria for GH deficiency?Failure of 2 stimuli to raise basal GH, IGF-1.
    Stimulation agents: Insulin, glucagon, arginine, clonidine.
    (Induce hypoglycaemia)
  12. 12Thyroid: Predominantly T4. T3 (active form) is derived from peripheral conversion of T4. Only free forms are active. What is T3/T4 usually bound to?Thyroxine-binding globulin (TBG), TBPre-Albumin, Albumin.
  13. 13What happens to thyroid hormones in pregnancy? Would you see a raise in FT3/FT4?In pregnancy, there is an increase of TBG and total thyroid hormones but serum FT3 / FT4 will remain the same.
  14. 14What TSH and FT4 profiles would you see in thyrotoxicosis (hyper) and hypothyroidism?Thyrotoxic: Low TSH, High FT4.
    Hypothyroid: High TSH, Low FT4.
  15. 15What is the clinical picture of someone with primary hypothyroidism?Myxoedema, lethargic, weight gain, cold intolerance, coarsening of hair and skin (lateral 1/3 of eyebrows!), slow reflexes, hoarseness, constipation, menstral abnormalities, bradycardia.
  16. 16What biochemical profile is seen in compensated hypothyroidism?High TSH
    Normal FT4
    TPO antibodies
    Rx: Thyroxine replacement
  17. 17In what special circumstance would you give T3 instead of T4 in thyroxine replacement?If patient has thyroid cancer and needs thyroxine to suppress TSH - some patients may be given T3.
  18. 18What biochemical profiles would you see in assessment of thyroxine replacement for: Adequate / Ideal Inadequate Irregular compliance / dose change Adequate / Over Over- replacementIdeal - Normal TSH, Normal FT4
    Inadequate - High TSH, Low FT4
    Irregular compliance - High TSH, norm FT4
    Adequate / Over - Low TSH, High / norm FT4 and FT3
    Over - Low TSH, High FT4
  19. 19What is the risk of over-replacement of thyroxine in hypothyroidism?Risk of Atrial Fibrillation (AF).
  20. 20What is the biochemical and clinical picture of someone with primary hyperthyroidism? (Graves' disease - Autoimmune)Low TSH, Elevated T4/T3.
    Weight loss, heat intolerance, palpitations, agitation, tremor, muscle weakness, diarrhoea, thyroid eye disease, menstral abnormalities.
  21. 21What is the swinging effect in hyperthyroidism? How is this prevented?Medication to treat hyperthyroidism causes transition into hypothyroidism.
    Rx: "BLOCK & REPLACE"
    Give thyroxine after block to prevent swing.
  22. 22How is hyperthyroidism treated?1. Antithyroid drugs: Carbimazole / Propylthiouracil (PTU).
    2. Surgery: Total or subtotal thyroidectomy
    3. Radio-iodine 131
  23. 23What is the most important side effect of carbimazole?Agranulocytosis.
    SICK DAY RULES: If sore throat, stop stat. and check WBC.
    !! Risk of neutropenic sepsis - S. pyogenes.
  24. 24How long do you keep a patient on carbimazole or PTU for? Why do you stop?2 year course.
    Check if relapse (50%) - If yes, consider surgery or radio-iodine treatment.
    This is because of the risk of neutropenic sepsis which can be lethal hence you don't want to keep patients on this long-term.
  25. 25What is given in preparation for surgical thyroidectomy for hyperparathyroidism? Why?Give potassium iodide (KI) to prevent "thyrotoxic storm" due to paralysis of iodine intake.
  26. 26What else may suppress TSH? (2º hypothyroidism)Low TRH (suppressed by FT4 / FT3).
    IL-1 / TNF - cytokine response to illness.
    Somatostatin,
    Glucocorticoids - steroid rx or stress.
    Dopamine.
  27. 27What is the effect of amiodarone on thyroid function? Lithium? Steroids? Beta-blockers? Anti-convulsants?Amiodarone: either hypo or hyperthyroidism due to iodine content.
    Lithium: High TSH, low T3/4
    Steroids: Low TSH, normal T4, low T3
    Beta-blockers: Low TSH, normal/high T4, low T3
    Anti-convulsants: Normal TSH, low T4, Normal T3
  28. 28If a patient has normal TSH does this exclude hypothyroidism?NO.
    Does not exclude 2º hypothyroidism, check FT4 in patient with pituitary disease!
  29. 29A patient has raised TSH and raised FT4 / FT3. What could cause this profile?TSH-secreting tumours.
  30. 30What are the layers of the adrenal gland and what do they secrete?Zona Glomerulosa - Aldosterone
    Zona Fasciculata - Cortisol; Androgens
    Zona Reticularis - Cortisol; Androgens
    Adrenal Medulla - A / NA
  31. 31What is the precursor to adrenal steroids?Cholesterol
    Adrenal steroids:
    1.Aldosterone
    2. Cortisol
    3. DHEA --> Testosterone (peripheral conv.)
    4. DHEA --> Oestradiol
  32. 32Cortisol is 90% protein bound, only the free faction is physiological active. What are the physiological effects of cortisol?1.Carbohydrate metabolism (x insulin, gluconeogenesis).
    2. Protein catabolism / breakdown.
    3. Immunosuppression.
    4.Permissive action - catecholamines, ADH
    5. Melanocyte-stimulating hormone - pigmentation
  33. 33How is cortisol released? (rhythm, triggers)Strong diurnal rhythm.
    Affected by stress.
  34. 34What are the causes of adrenal failure and what is used to differentiate them?1º: Congenital adrenal hyperplasia.
    Selective destruction of cortex; total adrenal destruction. Electrolyte changes.
    HIGH ACTH.
    2º: Steroids, infections, amyloidosis, mets.
    No electrolyte changes.
    2º adrenal insufficiency - LOW ACTH.
    Hypothalamo - pit. defect - HIGH / LOW ACTH
  35. 35What are the physiological changes in adrenal insufficiency?Hypoglycaemia
    Hyponatraemia
    Hyperkalaemia
    Hypotension (low peripheral resistance)
    Pigmentation (MSH)
    Vitiligo (?auto-immune)
    Gum inflammation
    Hypovolaemia (N&V, dehydration)
  36. 36What laboratory test is used to investigate / diagnose adrenal insufficiency?Synacthen test
    IM ACTH --> cortisol changes in 60m.
    Normal = >420 nmol rise
    Early Failure = <420 rise
    Addison's 1º failure = no change.
    (Unwell patient: Very high cortisol throughout)
  37. 37What biochemical changes are seen in Addison's disease? (1º adrenal insufficiency)Hyponatraemia
    Hyperkalaemia
    Volume Depletion
  38. 38What deficiency is in congenital adrenal hyperplasia (CAH)?21 Hydroxylase deficiency.
    Converts progesterone to 17-OH (cortisol).
    Deficiency = no cortisol feedback = over / under production of androgens.
  39. 39What clinical features are seen in Congenital Adrenal hyperplasia (CAH)?Newborn: Ambiguous external genitalia, pigmented scrotum, salt wasting, death.
    Adult: Hirsutism, menstrual disorder, subfertility.
  40. 40What is the marker used in investigating for Congenital adrenal hyperplasia (CAH)?Raised 17alphaOH progesterone.
  41. 41What is the difference between Cushing's disease and Cushing's syndrome? (Hypercortisolism)Cushing's disease = Pituitary Tumour
    Cushing's syndrome = ACTH-releasing tumour outside of pituitary (e.g. lungs, adrenals)
    HIGH ACTH
  42. 42What are other causes of hypercortisolism?Adenoma***
    Carcinoma**
    Iatrogenic - Steroids
    Pseudo-Cushing's - Alcohol abuse, obesity, depression (2º causes).
    LOW ACTH
  43. 43Clinical Features of Cushing'sMental disturbances.
    Moon face.
    Truncal obesity + Abdo striae.
    Hyperandrogenism: hirsutism, acne, amenorrhoea.
    Increased protein catabolism: osteoporosis, poor wound healing, thin skin - bruising.
    Insulin resistance: glucose intolerance, salt retention, HTN.
    Immunosuppression.
  44. 44What investigations do you do for excess cortisol?1. Serum cortisol
    2. Salivary cortisol
    3. Urine free cortisol (24h).
    ** 4. DEXAMETHASONE SUPPRESSION **
    5.BIPSS - pit. ACTH only.
  45. 45What do the results of dexamethasone suppression suggest? 1. 1mg Overnight 2. Low dose dexamethasone 3. High dose dexamethasone1. <50nmol cortisol is normal.
    False -ve = Cyclical Cushing's.
    2. Normal = suppressed.
    Cushing's = no suppression.
    3. Pituitary Cushing's = suppressed.
    Adrenal / Ectopic = no suppression.
  46. 46What is sub-fertility?Low probability of conception due to physiological damage / defect or 2º endocrine cause.
  47. 47What hormone change indicates ovulation?Progesterone rise >30 in luteal phase.
    ("Day 21" - 7 days before menses)
  48. 48What are the broad causes of anovulation (oligo/amenorrhoea) excluding uterine abnormalities or pregnancy?1. Primary Ovarian Failure (Impaired follicular development, ovaries dysfx).
    2. Secondary Ovarian Failure (Impaired LH/FSH production & follicular dev.).
    3. Polycystic Ovarian Syndrome (PCOS).
  49. 49What are the biochemical profiles of: 1º Ovarian Failure 2º Ovarian Failure PCOS1º Failure = High LH/FSH, Low oestradiol
    2º Failure = Low LH/FSH, Low oestradiol
    PCOS = High LH, normal FSH, High LH:FSH ratio, High testosterone
  50. 50What are the causes of primary ovarian failure?Premature ovarian insufficiency.
    Post-menopausal.
    Autoimmune.
    Damage.
    Surgery.
    Irradiation.
    Dysgenesis (Turner's Syndrome).
  51. 51What hormone's levels is used to diagnose 1º ovarian failure?FSH
    Test in women 40-45y or below (premature menopause)
  52. 52What are the causes of 2º ovarian failure?LHRH deficiency (Kallman's)
    Prolactinoma (pituitary)
    Functional 2º hypopituritism
    Systemic disease (thyroid, adrenal)
  53. 53What clinical signs are seen in PCOS?Oligomenorrhoea / Amenorrhoea
    Obesity & Insulin resistance
    Increased CVS risk
    Hirsutism
    Oestrogenisation (endometrial ca. risk)
  54. 54What histological changes are seen in confirmed PCOS?>15 cysts around cortex echogenic stromal compartment.
  55. 55What inhibits and stimulates Prolactin production?Inhibited by Dopamine.
    Stimulated by TRH.
  56. 56What are the causes of hyperprolactinaemia?Physiological: Pregnancy, stress, drugs (dopamine antag., oestrogen), macroprolactinoma.
    Pathological: Pituitary tumour (prolactin-secreting adenoma, acromegaly), lesions of hypothalamus / pit. stalk, 1º hypothyroidism, chronic renal failure.
  57. 57What is the normal level of prolactin? What do increased levels mean?<700 = Normal
    700 - 1000 = Doubtful macroprolactinoma
    1000 - 2000 = MicroPRL, meds, PCOS, thyroid
    2000-4000 = MicroPRL, hypothalamic dysfx
    4000 - 6000 = Prolactinoma
    >6000 = Macroprolactinoma
  58. 58Causes of Male Subfertility?Testicular: Hypergonadotrophic hypogonadism, isolated germinal compartment failure, non-endocrine (obstructive azoospermia, retrograde ejaculation)
    Hypothalamic / Pituitary: Hypogonadotrophic hypogonadism.
  59. 59When taking levels of testosterone, what needs to be taken into account? How is this quantified?Testosterone has a strong diurnal rhythm.
    Note time of test - Testosterone index.
  60. 60In pregnancy, what endocrinological changes can be seen?Raised oestrogen, progesterone, prolactin, hCG.
    Lowered LH / FSH.
  61. 61Lowered renal threshold for glucose in pregnancy can cause what?Gestational diabetes.
    Dx: blood glucose, random / fasting glucose, GTT.
    Screen those with risk factors.
  62. 62What are the early / late signs of pregnancy induced hypertension / pre-eclampsia?Early: HTN, increased urate.
    Late: Low GFR, proteinuria, oedema, increased urea / creatinine.
    Late Complication: HELLP syndrome.
  63. 63What is HELLP syndrome?Haemolysis
    Elevated Liver enzymes (ALT)
    Low Platelets
  64. 64Liver disease in pregnancy1. Pre-eclampsia
    2. HELLP syndrome
    3. Hyperemesis Gravidarum
    4. Acute fatty liver of pregnancy
    5. Obstetric cholestasis - generalised pruritis in 3rd trimester
  65. 65What are the functions of the kidney?1. Excretion of metabolic waste products
    2. Water & solute homeostasis
    3. Synthetic activity (renin, vit. D, EPO)
    4. Removal of drugs / toxins.
  66. 66What mechanisms contribute to the glomerular filter?1. Size exclusion.
    2. -ve charged molecules repelled.
    3. Permeability.
  67. 67What is acute kidney injury? How is it staged?AKI = Any physical, chemical, toxic, or ischaemic insult causing raised creatinine or low urine output over hours / days.
    Stage 1 = 1.5 - 2x creat rise from baseline
    Stage 2 = 2 - 3x creat rise from baseline
    Stage 3 = >3x creat rise from baseline
  68. 68Causes of AKIPre-renal: Hypovolaemia / Hypoperfusion, Pump Failure.
    Renal: Ischaemia***, nephrotoxins, glomerulonephritis, interstitial nephritis.
    Post-renal: Stones, tumour, prostate.
  69. 69How do you differentiate pre-renal uraemia and renal tubular necrosis? How do management differ?Pre-renal uraemia: U[Na] <20. GIVE FLUIDS.
    Renal Tubular Necrosis: U[Na] >20.
    DO NOT GIVE FLUIDS, will overload.
  70. 70What are the clinical features of AKI?Failure to remove nitrogenous waste: Nausea, Malaise, Confusion
    Fluid overload: CCF, Oedema
    Acidaemia
    Potassium retention: Dysrhythmias
  71. 71What is Fanconi's syndrome?Renal globular tubular defect
  72. 72Renal tubular disorders: Transport defects Glucose Amino acids Phosphate Hydrogen ionGlucose - Renal glycosuria
    Amino acids - Selective-cystinuria
    Phosphate - Hypophosphataemic rickets
    Hydrogen ion - Renal tubular acidosis
  73. 73Where is ADH (vasopressin) produced and what is its action?Produced by hypothalamus, stimulated by decrease in circulating volume; drugs, pain, stress.
    Opens aquaporin channels in collecting duct --> Water reabsorption.
    ADH only acts in severe hypotension.
    Main regulator: Aldosterone
  74. 74What is the mechanism of aldosterone in the distal tubule?Na resorption, K excretion.
  75. 75What is eGFR estimated from? What does it depend on?Serum creatinine.
    Age, sex, race.
  76. 76Chronic kidney disease is the gradual irreversible fall in renal function. CKD Aetiology?DM nephropathy, HTN
    Polycystic kidney disease
    Glomerulonephritis, pyelonephritis, interstitial nephritis
    Multisystem Disease
    Drugs
  77. 77How is CKD staged?1 = eGFR >90 + structural / proteinuria
    2 = eGFR 60 - 90 + structural / proteinuria
    3a = eGFR 45 - 60 = Mild/Moderate
    3b = eGFR 30 - 45 = Moderate
    4 = eGFR 15 - 30 = Severe
    5 = <15 = ESRF, dialysis.
    3b onwards has clinically relevant sequelae.
  78. 78What are the consequences of CKD?3a = Hypertension, CVD risk
    3b = Low calcium, 2º hyperparathyroidism
    4 = Anaemia, anorexia, high phosphate
    5 = Salt/water retention, acidosis, hyperkalaemia
  79. 79What are the actions of PTH?Stimulates bone resorption
    Increase renal Ca reabsorption
    Decrease renal PO4 reabsorption
    Increase gut Ca absorption
    NET: Increase Ca, Lower PO4
  80. 80What are the actions of Vitamin D?Increase Ca absorption in small intestine.
    Promotes bone growth by raising Ca / PO4.
    Synergistic action with PTH when Ca low.
    Increase renal reabsorption of Ca / PO4.
    NET: Increase Ca / PO4.
  81. 81Where is calcitonin produced? What are the actions of calcitonin?Produced by parafollicular C cells of thyroid
    Inhibits osteoclasts, reduce bone resorption.
    Reduce renal resorption of Ca / PO4.
    NET: Reduce Ca / PO4.
  82. 82What is calcitonin used for clinically?Tumour marker.
    Treatment for hypercalcaemia, paget's disease.
  83. 83What are some clinical symptoms / signs of hypercalcaemia?Renal - Polyuria (D.I.), Renal calculi
    GI - Anorexia, N&V, constipation, abdo pain, peptic ulcers.
    CNS - Depression, fatigue, confusion.
    CVS - Short QT interval, bradycardia
    Bony pain
  84. 84Treatment of hypercalcaemia?1. Rehydration ***
    2. Bisphosphonates *
    3. Steroids (cancer)
    4. Others - oral phosphates, calcitonin, cinacalet.
  85. 85Aetiology of Hypercalcaemia? (Incl. classification)1. Artifactual - dehydration, prolonged tournaquet
    2. Excessive Ca Intake - Too much Vit D, Sarcoidosis
    3. Increased bone resorption -
    1º hyperparathyroidism*, malignancy*, thyrotoxicosis, immobilisation
    4. Increased renal absorption - Thiazides, FHH
  86. 86Clinical Features of 1º hyperparathyroidism?RAISED PTH.
    Asymptomatic
    Hypercalcaemic symptoms
    Stones
    GI disorders
    Bone disease (osteitis fibrosa cystica)
  87. 87What malignancies may cause hypercalcaemia?1. Humoral hypercalcaemia - resorptive factors release (PTHrp, TNF, IL-1)
    2. Metastatic hypercalcaemia - Ca breast, lung, prostate.
    3. Dysregulated Vit.D metabolism - esp. haematological ca.
  88. 88What clinical features may be seen in hypocalcaemia? What are the eponymous tests / signs?Neuro: Lethargy, depression, psychosis, tetany, parasthesia, cramps.
    CVS: Long QT, arrhythmias.
    Soft tissue: Cataracts, brittle nails / hair.
    CHOVSTEK'S - Face spasm on tapping
    TROUSSEAU'S - Carpopedal spasm when blood pressure cuff inflated >3min
  89. 89What are the classification of causes for hypocalcaemia?*Thyroid / Parathyroid surgery: May have transient hypocalcaemia.*
    1. Artifactual - Low plasma albumin, unsuitable sample.
    2. Low intake - Vit. D deficiency*
    3. Low Ca from bone - PTH deficiency / resistance*, anti-resorptive agents.
    4. Increase Ca from bone - Hungry bone syndrome *
    5. Extraskeletal sequestration - Acute pancreatitis*
  90. 90What can cause Vit. D deficiency?Reduced intake: Malnutrition / Malabsorption, Lack of sunlight exposure.
    Impaired Metabolism: Renal disease, anticonvulsant therapy (epileptics).
  91. 91What are the consequences of Vit. D deficiency in adults and children?Children: Rickets
    Adults: Osteomalacia
  92. 92Causes of hypoparathyroidism?PTH Deficiency: Surgical, congenital - Di George syndrome, Idiopathic, Infiltrative.
    PTH resistance - Mg2+ deficiency, pseudo-hypoparathyroidism.
  93. 93What is Hungry Bone Syndrome?Parathyroid removal --> No PTH --> No bone resorption --> CA INFLUX INTO BONE.
  94. 94How does acute pancreatitis lower serum Ca?Release of digestive enzymes in acute pancreatitis binds Ca to free FA.
    Hence serum Ca is a good marker of disease progression - GRANSON'S CRITERIA.
  95. 95How is hypocalcaemia treated?1. Diet
    2. Oral Ca Supplements
    3. Oral vitamin D ***
    4. IV calcium gluconate
  96. 96How is Osmolality calculated?2[Na+K] + Urea + Glucose
  97. 97What can acute hyponatraemia cause?Expansion of intracellular space --> Cerebral oedema --> Confusions, convulsions, coma.
  98. 98What are the different causes of hyponatraemia?1. Pseudo-hyponatraemia (lipidaemia / hyperproteinaemia)
    2. Compensatory hyponatraemia (hyperglycaemic)
    3. Volume depleted - Renal loss
    (diuretics, addisons)
    4. Volume depleted - Extra-renal loss
    (vomiting, diarrhoea)
    5. Euvolaemic - SIADH, hypothyroid
    6. Volume expanded - oedema
    (Nephrotic, cirrhosis, heart failure)
  99. 99Water and Na are usually lost together (e.g. Addison's, D&V). Why would this cause hyponatraemia in severe cases?Excessive volume depletion --> ADH activation --> Water retention but Na continues to be lost --> Hyponatraemia.
  100. 100SIADH is caused by excessive ADH leading to dilutional hyponatraemia. How is this diagnosed?URINE CONCENTRATION
    Low plasma osmolality with concentrated urine.
  101. 101What causes SIADH?Neoplasia (bronchial / pancreatic ca, lymphoma) - Ectopic ADH.
    Pulmonary disorders - hypothalamal stimulation.
    Neurotoxic - encephalitis, meningitis, head injury, porphyria.
  102. 102How is SIADH managed?Treat underlying cause.
    Fluid restriction, demeclocycline, tolvaptan (ADH antag).
  103. 103Why does hyponatraemia need to be corrected slowly?Rapid correction can lead to central pontine myelinosis and neuro cell death!!!
    (Dementia)
  104. 104How does liver cirrhosis cause hyponatraemia?Low albumin --> Low intravascular vol. -->
    + Aldosterone --> Na / water retention.
    This cannot continue --> ADH --> Hyponatraemia.
  105. 105How is liver cirrhosis-induced hyponatraemia treated?Lying down to encourage Na / water clearance, furosemide diuretic.
    Rx: Aldosterone antagonist, spironolactone, treat underlying cause.
  106. 106What are some causes of hypernatraemia?1. Inadequate water intake
    2. Impaired water retention
    (D.I., osmotic diuresis)
    3. Loss of hypotonic fluids
    (sweat, hyperventilation, watery diarrhoea, burns)
    4. Excessive sodium intake
    (IV fludis, drugs - abx)
    5. Increased sodium retention
    (1º aldosteronism, Conn syndrome)
  107. 107What is Diabetes Insipidus and what tests can be used to diagnose it?D.I. = ADH insufficiency, water depletion with polydipsia and polyuria.
    (high NA + urea)
    Water Deprivation Test -
    Normal = Rise in urine osmolality
    DI = No rise in osmolality
    (BEWARE DEHYDRATION / LETHAL NA)
    Desmopressin Test (synthetic ADH) - Cranial or Nephrogenic DI
  108. 108What regulates potassium concentration in the kidneys (DCT)? In any cell?Na/K/H pump.
    DCT: Na resorption stimulated by aldosterone.
    Metabolic alkalosis = hypokalaemia
    Metabolic acidosis = hyperkalaemia
    In any cell:
    Catecholamines Increase K+ resorp.
    Insulin decrease K+ resorp.
  109. 109Clinical features of hypokalaemiaHypotonia
    Paralytic ileus
    Hepatic encephalopathy
    Polyuria
    Cardiac dysrhythmias - U WAVES.
    Rx: Oral Sando-K or IV K if oral impossible.
  110. 110What can cause hypokalaemia?Renal: alkalosis, drugs (diuretics), mineralcorticoid excess, kidney disease, other electrolyte disturbance.
    Extra-renal: GI loss, EC-IC shift (insulin, catecholamines, refeeding syndrome), Inadequate intake (alcoholism, anorexia).
  111. 111Clinical features of HYPER-kalaemia?ECG: Tall tented T waves / sine wave
    Bradycardia
    Cardiac arrest
  112. 112Causes of hyperkalaemiaRenal: renal failure (AKI**, CKD), Drugs (K+ sparing diuretic, ACE-i), mineralcorticoid deficiency.
    Extra-renal: pseudohyperkalaemia, high K input, IC-EC shift (acidosis, hypoxia, insulin deficiency).
  113. 113How is hyperkalaemia treated?Calcium gluconate
    Salbutamol
    Insulin + 50% dextrose
    NaHCO3
    Calcium Resonium
    Haemofiltration / Dialysis
  114. 114What are the 4 classifications of MI?1. Plaque rupture with thrombosis.
    2. Vasospasm / endothelial dysfunction.
    3. Fixed atherosclerosis + supply / demand imbalance.
    4. Supply / Demand imbalance only (Blood loss; low BP)
  115. 115What's the difference between NSTEMI and STEMI?NSTEMI: Subendocardial
    ST depression, T inversion
    Reversible ischaemia
    STEMI: Transmural necrosis
    ST elevation
    Irreversible necrosis
  116. 116Aside from ACS, what else may elevate troponin levels?CCF
    Renal failure
    Sepsis
    AF
    Myocarditis
    Rhabdomyolysis
    PE
    AAD
    Electric burns
    Trauma
    Chemotherapy
  117. 117What are the following used for? High sensitivity Troponin Myoglobin CKMB FABP Pro-BNPHigh Sensitivity Trop: Rule in / out MI.
    Myoglobin: Rule out MI.
    CKMB: Use in re-infarction w/ trop.
    FABP: Myocardial lipid synthesis.
    BNP: CCF diagnosis and prognostic indicator.
  118. 118What conditions can cause endocrine hypertension?Cushing's
    Conn syndrome
    Hyperparathyroidism
    Phaeochromocytoma
    Acromegaly
    Hyperthyroidism
  119. 119What is pheochromocytoma? What can it cause?Catecholamine-secreting tumour.
    Labile HTN, paroxysmal symptoms, HTN crisis.
    Malignant --> Renal dysfunction.
  120. 120Clinical Features of pheochromocytoma?Sweating, palpitations, weight loss, headache.
  121. 121What is Conn's Syndrome?Mineralcorticoid excess --> +RAAS
    HTN, hypokalaemia, alkalosis.
    1º: Adrenal Adenoma.
    2º: Raised Renin.
  122. 122How to investigate Conn's Syndrome?Plasma aldosterone: renin activity ratio.
    (NO diuretics / ACE-i)
    Conn's: Low renin, high aldosterone
    2º Hyperaldosteronism: High renin, high aldosterone
  123. 123What does hypercholesterolaemia and hypertriglyceridaemia cause?Hypercholesterolaemia: Atherosclerosis
    HyperTCG: Atheroma (mild/mod), pancreatitis (severe).
  124. 124What is familial hypercholesterolaemia?Autosomal dominant.
    Defective receptor (LDL-r / APO-B / PCSK9)
    --> Raised LDL (no clearance) --> Atherosclerosis
    Massive CVD risk. Rx Diet + Statins.
  125. 125How does diabetes and smoking contribute to CVS disease?Diabetes: small dense LDL more atherogenic and easily oxidised --> accelerated vascular disease.
    Smoker: Oxidation of LDL --> Endothelial damage.
  126. 126What causes 2º hyperlipidaemia?DM, liver disease, renal (nephrotic syndrome), hypothyroidism
    Alcohol, HIV, anorexia
    Drugs (anti-retrovirals, retinoids, steroids)
  127. 127What drug treatments are used for hyperlipidaemia?(Lifestyle changes! 1º/2º prevention)
    1.Cholesterol - Statins, Ezetimide
    2. TCG - Fibrates, omacor (fish oil)
    3. New therapy - PCSK9-i, Gene replacement, Gene suppression
  128. 128How do the following drugs work? Statins Ezetimide Fibrates Omacor PCSK9-inhibitorStatins - HMG-CoA Reductase inhibitors
    Ezetimide - Cholesterol absorption inhibitor
    Fibrates - Stop VLDL production
    Omacor - Inhibit enzyme for TCG synthesis
    PCSK9-inhibitor - Stop LDL-r breakdown, increase clearance
  129. 129How are inherited metabolic disorders (IMD) classified?1. Disorders of complex molecules
    (Permanent / progressive symptoms independent of illness or food intake)
    Lysosomal storage disorders
    2. Intoxication
    (Accumulation of toxic compounds proximal to metabolic block)
    Hyperammonaemia
    3. Impaired energy metabolism
    (Deficiency in energy production and utilisation)
    FA oxidation defects, MCADD
  130. 130What are the main roles of serum albumin? Albumin is synthesised by the liver.Transport
    Oncotic pressure (circulatory vol.)
  131. 1314 Causes of hypoalbuminaemia1. Reduced synthesis - liver disease, malnutrition / malabsorption.
    2. Increased catabolism - severe illness incl. sepsis, trauma, malignancy.
    3. Excess loss - renal, GI, burns.
    4. Haemodilution - iatrogenic, oedema from CCF, CLD, pregnancy.
  132. 132How is albumin redistributed?1. Plasma - Interstitium (acute change)
    2. Increased permeability in e.g. sepsis.
    3. Recumbency (postural. small change.)
  133. 133Consequences of low albumin1. Reduced oncotic pressure - fluid leaks / 3rd spacing - oedema
    2. Reduced binding capacity - transport released (e.g. Ca); potential drug toxicity.
  134. 134What is the definition of proteinuria?Protein dip-stick detects albumin >300mg/L
    (normal = <30mg/24h)
  135. 135What is the albumin-creatinine ratio (ACR) used for?Screening marker for renal disease, CVD morbidity and mortality.
    3.0-30g/mol = Microalbuminuria
    30-70 = Proteinuria
    70-250 = Proteinuria
    >250 = Nephrotic
  136. 1364 Causes of proteinuria?1. Glomerular - nephrotic syndrome
    2. Overflow - excess proteins
    3. Post-renal - UTI, tumour, contamination
    4. Tubular - tubular damage, impaired resorption
  137. 137What's the difference between transudates and exudates?Transudates - "FAILURES"
    Low in protein, across capillary endothelium.
    Exudates - "PUS"
    High in protein, due to inflammatory process / permeability.
  138. 138Low levels of protein in the CSF is normal (plasma ultrafiltration), however raised proteins may be pathological. List some causes of this.Infection
    Chronic inflammation
    Blocked spinal cord (tumour, #)
  139. 139Hypergammaglobulinaemia can be separated via serum protein electrophoresis into what 2 categories? What are the causes?Polyclonal
    (Inflammation, infection, autoimmune, CLD)
    Monoclonal
    (Multiple myeloma, Waldenstrom's, macroglobulinaemia, MGUs, B cell malignancy)
  140. 140What does alpha-1-antitrypsin deficiency predispose someone to?Early onset emphysema & CLD.
    (Candidate for lung transplant)
  141. 141What is the function of haptoglobin? In what condition is it low?Fx: Prevents iron loss by binding to free Hb from intravascular haemolysis.
    Low in haemolytic anaemia**, chronic lung disease (CLD), mets, sepsis.
  142. 142What is the function of caeruloplasmin? In what condition is it low? When could it be increased?Caeruloplasmin is a copper carrying protein. Fx: oxidoreductase & iron transport.
    Low in Wilson's Disease.
    Increased in acute phase, pregnancy, OCP.
  143. 143What is the triad of symptoms in nephrotic syndrome?Proteinuria
    Hypoalbuminaemia
    Hyperlipidaemia (compensatory)
    Oedema
  144. 144Albumin is measured with every calcium level test to give corrected calcium. How is this calculated?Measured calcium + 0.2(40-Albumin)
  145. 145What can trigger ADH release?Hypoosmolar (ECF osmolality > ICF)
    Hypovolaemia
    Stress (pain, nausea)
    Drugs (e.g. Analgesics / Anti-depressants)
  146. 146What factors contribute to the increased secretion of renin?1. Low sodium intake
    2. Low arterial pressure
    3. Low renal blood flow
  147. 147What is indicated by a Pepperpot skull on XR?Hyperparathyroidism
  148. 148How are inherited metabolic disorders (IMD) classified?1. Disorders of complex molecules
    (Permanent / progressive symptoms independent of illness or food intake)
    Lysosomal storage disorders
    2. Intoxication
    (Accumulation of toxic compounds proximal to metabolic block)
    Hyperammonaemia
    3. Impaired energy metabolism
    (Deficiency in energy production and utilisation)
    FA oxidation defects, MCADD
  149. 149IMD: What is lysosomal storage disorders?Accumulation of partially degraded substances within lysosome --> disturbed cell homeostasis and early cell death.
  150. 150Which cells are most vulnerable to damage in lysosomal storage disorders?Cells with low turnover (neurons) or rich in lysosomes (WBC).
  151. 151How does lysosomal storage disorders typically present?3-6 months old
    Neurological symptoms
    Hepatosplenomegaly
    CVS / RS / Bone problems
    Life threatening multi-organ disease
  152. 152Classification of lysosomal storage disorders1.Mucopolysacharidosis LSD - glycosaminoglycans
    2.Oligosaccharidosis - Oligosaccharides
    3. Sphingolipodosis - Glycosphingolipids
    4. Others
  153. 153How to treat lysosomal storage disorders?Supportive / Palliative
    Enzyme replacement therapy
    Bone marrow transplant
    Substrate reduction
    Chaperone and Gene Therapy
  154. 154IMD - Intoxication Clinical features of acute / chronic?Acute - Vomiting, lethargy, coma, liver failure.
    Chronic - Progressive developmental delay, cardipmyopathy
    e.g. Hyperammonaemia
  155. 155What levels of ammonia constitutes hyperammonaemia? a) Premature neonate b) Term neonate c) Infanta) >150 micro-mol/L
    b) >100
    c) >40
  156. 156Clinical presentation of hyperammonaemiaAcute tachypnoea
    Lethargy
    Vomiting
    Convulsions
    Encephalopathy
    (irreversible neurological damage if not treated)
  157. 157Pathway of normal ammonia detoxificationCPS1 enzyme --> Urea, glutamine, orotic acid
  158. 158Causes of hyperammonaemia1. Artifactual
    (delayed analysis, haemolysis, struggling infant)
    2. Non-metabolic
    (Hepatic failure, UTI, parental nutrition, hypovolaemic shock)
    3. Urea cycle defect (inherited)
    4. Other inherited disease
    (Organic acidurias, FA oxidation defects, HHH syndrome)
  159. 159Acute management of hyperammonaemiaStop protein intake
    Glucose infusion
    Arginine
    (Sodium benzoate / phenylbutyrate)
    (Haemofiltration)
  160. 160Chronic management of hyperammonaemiaLow protein diet
    Benzoate + Phenybutyrate
    Argine + Citrulline
    (liver transplant)
  161. 161IMD - impaired energy metabolism Symptoms ExamplePC: Hypoglycaemia, hyperlacticacidaemia, hypotonia, myopathy, cardiomyopathy, SUDIs
    E.g. FA oxidation defects, glycogenesis, gluconeogenesis defect, mitochondrial resp. chain disorders
  162. 162An example of FA oxidation defect is MCADD - Medium-chain acyl-CoA dehydrogenesis deficiency. How does this present?Metabolic crisis precipitated by fasting, illness, operations; occasionally asymptomatic.
    Strong Family History!
  163. 163How to diagnose MCADD?Mutation analysis
    Organic acids
    Acylcarnitines
  164. 164How to treat MCADD? Acute / ChronicAcute - IV glucose + Insulin, IV Carnitine
    Chronic - Avoid fasting, low fat high carbohydrate diet, oral carnitine, emergency regime
  165. 165How to diagnose inborn error or metabolism (IEM)?Initial metabolic screen (bloods, urine)
    Specific tests
    Non-biochem tests
    Confirmatory tests
    Family studies
    Newborn screening
  166. 166How to manage iEM?Control substrate accumulation
    Increase substrate removal
    Replace deficient product
    ERT
    Cofactor replacement therapy
    Bone marrow transplant
    Organ transplant
    Chaperone & gene therapy
  167. 167Familial combined hyperlipidaemiaAD-inheritance
    High cholesterol, High TCG
    Overporoduction of VLDL by liver
    Rx. Statins
  168. 168Type 3 hyperlipidaemiaHigh cholesterol & TCG
    High IDL
    Apo E2:E2
    Alcohol excess, poor diet.
    Palmar crease xanthomata!
    Rx. Statin +/- Fibrates
  169. 169Severe Hypertriglyceridaemia>10mmol/L TCG. Mostly genetic - lipoprotein lipase deficiency, type 1 hyperlipidaemia)
    Worsened by lifestyle.
    Clin: Eruptive xanthomata, lipaemia retinalis, risk of acute pancreatitis
    Rx. Fibrates

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UoB Pathology 2018
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