Clinical chemistry Flashcards

1
Q

Normal renal function (3)

A
  1. excretory
  2. regulatory - blood vol, osmolality, electrolytes and pH
  3. endocrine - EPO, renin, 1a-hydroxylase production (important for vit D)
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2
Q

Normal glomerular filtration rate

A

90-150ml/min

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3
Q

What is creatinine and what is it affected by?

A

Breakdown product of creatine phosphate in muscle

Affected by: meat intake, muscle mass, some drugs

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4
Q

What can increase the plasma urea/creatinine ratio?

A
Increased protein intake
   GI bleed
   Dehydration
   Acute catabolic state    
Low muscle mass
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5
Q

What can reduce plasma urea/creatinine ratio?

A
Decreased protein intake
Liver failure 
Haemodialysis
SIADH
Increased muscle mass
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6
Q

What are the 4 types of proteinuria?

A

Glomerular - loss of large proteins, albumin first (glomerulonephritis and diabetes)

Tubular - loss of increasing amounts of low MW proteins, not albumin (fanconi syndrome)

Overflow - loss of low MW proteins with high plasma concentrations - filtration rate exceeds resorption capacity - free Hb, myoglobin, immunoglobulin light chains

Orthostatic - benign glomerular proteinuria in young adults, low risk to progress to renal disease

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7
Q

Diagnostic criteria of nephritic syndrome

A

(Glomerular proteinuria)
Proteinuria
Hypoalbuminaemia
Peripheral edema

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8
Q

Common causes of ESKF

A
Diabetic nephropathy
Glomerulonephritis
Hypertensive vascular disease 
Polycystic kidney disease
Reflux Nephropathy
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9
Q

Investigations for renal stones

A

Stone analysis
Plasma Ca PO4 uric acid
24 hour urinary Ca, oxalate
Spot urine microscopy, culture, pH

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10
Q

Increased anion gap metabolic acidosis causes:

A
M - methanol
   U – uraemia
   D – diabetic ketoacidosis
   P – propylene glycol and other glycols
   I – iron, isoniazid, inborn errors of metabolism
   L – lactic acidosis
   E – ethanol and other alcohols
   S – salicylates
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11
Q

Normal anion gap metabolic acidosis causes:

A

D – diarrhoea
R-RTA
A - Addisons
A – acetazolamide (carbonic anhydrase inhibitor)

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12
Q

Causes of hyponatraemia

A

Normal plasma osmolality - pseudohyponatremia, drip contamination

Increased plasma osmolality - hyperglycaemia, mannitol, glycine

Decreased plasma osmolality - true hyponatremia

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13
Q

If plasma sodium is low and plasma osmolality is normal, what is this phenomena called?

A

Pseudohyponatremia

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14
Q

How is hyperglycaemia related to hyponatremia

A

High glucose can draw water into the cells, this dilutes sodium concentration - causing hyponatremia

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15
Q

What is true hyponatremia

A

Low plasma sodium and osmolality caused by water gain or Na loss

Clinical feature: headache, confusion, lethargy, fatigue, appetite loss, muscle weakness, spasms
Dangerous <115mmol/L

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16
Q

Enzymes involved in steroidogenesis:

A
  1. Cytochrome P450 - contains a haem group to activate oxygen for oxidation reactions
  2. Steroid dehydrogenase - for alcohol/ketone/aldehyde interconversions and oxidation/reduction
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17
Q

Steroids proceed by the adrenal cortex

A

Cortisol (GC)
Corticosterone (GC+MC activity)
Aldosterone (MC)
Dehydroepiandrosterone (DHEA) - inactive androgen

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18
Q

What is the rate limiting step in steroidogenesis?

A

Cholesterol side chain cleavage: regulated by ACTH and catalysed by CYP11A1 (P450scc)

Involves 3 oxidations of the cholesterol side chain causing cleavage between C20 and C22

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19
Q

What does DHEA synthesis require?

A

Lyase activity of P450 17-alpha

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20
Q

What is the most common enzyme deficiency in congenital adrenal hyperplasia?

A

P450 21

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21
Q

Causes of hyperprolactinaemia

A

Physiological - stress, pregnancy, lactation, suckling

Pharmacological - dopamine receptor blockade, depletion of dopamine

Pathological - HP disorders, hypothyroidism, renal failure, seizures

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22
Q

What initiates secretion of prolactin?

A

Release of dopamine = inhibitory (causes release of prolactin) during Sleep, after meals, exercise and stress

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23
Q

What can cause spikes in growth hormone?

A
  • 3 hours after eating
  • after exercise
  • 90mins after onset of sleep
  • peak during deep REM sleep
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24
Q

Metabolic actions of GH

A
  • increases lipolysis and lipid oxidation
  • increases hepatic glucose production
  • increases protein synthesis
  • phosphate, sodium and water retention
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25
Q

Changes associated with acromegaly

A

Glucose intolerance

Hypercalcuria and hypercalcemia

26
Q

What causes the hyperkalemia and hyponatremia in adisons disease?

A

Mineralocorticoid/aldosterone deficiency = salt wasting and reduced potassium excretion

27
Q

What is diabetes insidious?

A

Relative or absolute lack of ADH resulting in inability to concentrate urine - polyuria, nocturia and polydypsia

28
Q

Thyroid tests

A
TSH
Free T4
Free T3
Thyroid antibodies - anti-TPO, Anti-TG
TSH receptor antibodies
29
Q

How to investigate hyponatremia

A

Blood gas sodium
Plasma osmolality
Urine Na and osmolality
Patient’s volume status

30
Q

True hyponatremia

A

Decreased plasma osmolality caused by water gain or sodium loss

31
Q

What is pseudohyponatremia?

A

Falsely low sodium rest caused by hyperlipidaemia or hyperproteinaemia

32
Q

Causes of true hyponatremia when urine Na+ <20mmol/L (non-renal)

A

Increase in volume - CCF, hypoalbuminaemia
N volume - polydypsia
Reduced volume - vomiting, diarrhoea, XS sweating

33
Q

Causes of true hyponatremia when urine Na+ >20mmol/L

A

Increase in volume - CRF
N volume - SIADH, hypothyroid, hypocorticolism
Reduced volume - diuretics, Addison’s, RTA, nephritis

34
Q

How does pH affect calcium?

A

Alkalosis reduces ionised calcium and increases bound calcium

Acidosis increased ionised calcium and reduces bound calcium

35
Q

What converts androstenedione to testosterone

A

17-beta-hydroxysteroid dehydrogenase

36
Q

What converts pregnenolone to progesterone

A

3-beta-hydroxysteroid dehydrogenase

37
Q

3 mitochondrial/ cytochrome P450 oxidation reactions involved in steroidogenesis

A

CYP11A1 - side chain cleavage

CYP11B1 - 11B hydroxylation

CYP11B2 - 18-hydroxylation

38
Q

3 microsomal oxidation reactions involving CYP450 involved in steroidogenesis

A

CYP17A1 = P450 17α (17-hydroxylase/lyase)

CYP21A2 = P450 21 (21-hydroxylation)

CYP19A1 = P450 aromatase (little in adrenal)

39
Q

Most common deficiency in congenital adrenal hyperplasia

A

P450 21 (CYP21A2)

40
Q

Causes of hyperprolactinaemia

A

Physiological: stress, pregnancy, lactation, suckling

Pharm: dopamine receptor blockade ro depletion of dopamine

Path: prolactinoma, stalk compression, hypothyroidism, renal failure, seizures

41
Q

How would you treat macroprolactinoma?

A

Dopamine agonist - cabergoline

42
Q

Where is GH synthesised?

A

Somatotropic (acidophilic) cells of the adenohypophysis

43
Q

Biochemical changes associated with acromegaly

A

Glucose intolerance

Hypercalcuria/calcemia

44
Q

Screening test for cushion’s syndrome

A

Overnight 1mg dexamethasone suppression (cortisol should be low in the morning, if high then tumour) OR
24 hour urinary free cortisol
OR
Midnight or salivary cortisol

45
Q

Hyponatremia and hyperkalemia in addison’s disease

A

MC (aldosterone) deficiency causes salt wasting (sodium) and reduced potassium excretion = hyperkalemia

Salt wasting due to urinary sodium loss results in hypovolemia so ADH is released and this causes hyponatremia

46
Q

Grave’s specific features in addition to hyperthyroid features

A
  • ophthalmology

- pre tibial myxoedema

47
Q

Causes of pseudohyponatremia in normal osmolality

A

Hyperlipidemia or hyperproteinemia

48
Q

Hyponatremia and hyperglycemia

A

Hyperglycemia draws fluid into intracellular compartment which dilutes Na+ causing hyponatremia. As glucose is corrected, fluid shifts back and hyponatremia resolves

Hyperglycemia also causes osmotic diuresis so patients can be hyper/normo/hyponatremic

49
Q

Clinical features of hyponatremia

A

N+V, headache, confusion, lethargy, fatigue, appetite loss, irritable, muscle weakness, LOC, seizures

50
Q

Non renal causes of true hyponatremia (<20mmol Na in urine)

A

↑volume - CCF, hypoalbuminaemia,
N volume - polydipsia,
↓ volume - vomiting, diarrhoea, excessive sweating

51
Q

Renal causes of true hyponatremia (>20mmol Na)

A

↑volume - CRF
N volume - SIADH, hypothyroid, hypocortisolism
↓ volume - diuretics, Addison’s, RTA, nephritis

52
Q

Diagnostic criteria for SIADH

A
Low plasma Na and osmolality
   Inappropriately high urine osmolality
   Urine Na >20mmol/kg
   Euvolaemia
   Normal renal, thyroid and adrenal function
   Not on diuretics
53
Q

Results in a person using a thiazide diuretic

A

Low sodium and potassium

High HCO3-

54
Q

Plasma investigation results in rhabdomylosis

A

High potassium
High U + C
V high creatine kinase

55
Q

How does pH affect binding of calcium to proteins in serum

A

Alkalosis →
↓ ionised calcium
↑ bound calcium

Acidosis →
↑ ionised calcium
↓ bound calcium

56
Q

K-EDTA, potassium and calcium plasma concentration results

A

K-EDTA binds K and shows high potassium, EDTA also chelates calcium which shows as low calcium

57
Q

Causes of respiratory acidosis

A

Thoracic disease
NM disease
CNS depression

58
Q

Causes of metabolic alkalosis

A

Antacids
Diuretics
Liquorice
Endocrine - cushion’s, CAH

59
Q

Causes of respiratory alkalosis

A

Central stimulation: anxiety, pregnancy, hypoxemia, infection, trauma

Pulmonary: embolism, acute pulmonary deem, asthma, pneumonia

60
Q

Causes of metabolic acidosis

A

Increased anion gap
Methanol, uraemia, DKA, glycols, iron, lactic acidosis,

Normal anion gap
Diarrhoea, RTA, Addisons,