Clinical chemistry Flashcards
Normal renal function (3)
- excretory
- regulatory - blood vol, osmolality, electrolytes and pH
- endocrine - EPO, renin, 1a-hydroxylase production (important for vit D)
Normal glomerular filtration rate
90-150ml/min
What is creatinine and what is it affected by?
Breakdown product of creatine phosphate in muscle
Affected by: meat intake, muscle mass, some drugs
What can increase the plasma urea/creatinine ratio?
Increased protein intake GI bleed Dehydration Acute catabolic state Low muscle mass
What can reduce plasma urea/creatinine ratio?
Decreased protein intake Liver failure Haemodialysis SIADH Increased muscle mass
What are the 4 types of proteinuria?
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
Diagnostic criteria of nephritic syndrome
(Glomerular proteinuria)
Proteinuria
Hypoalbuminaemia
Peripheral edema
Common causes of ESKF
Diabetic nephropathy Glomerulonephritis Hypertensive vascular disease Polycystic kidney disease Reflux Nephropathy
Investigations for renal stones
Stone analysis
Plasma Ca PO4 uric acid
24 hour urinary Ca, oxalate
Spot urine microscopy, culture, pH
Increased anion gap metabolic acidosis causes:
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
Normal anion gap metabolic acidosis causes:
D – diarrhoea
R-RTA
A - Addisons
A – acetazolamide (carbonic anhydrase inhibitor)
Causes of hyponatraemia
Normal plasma osmolality - pseudohyponatremia, drip contamination
Increased plasma osmolality - hyperglycaemia, mannitol, glycine
Decreased plasma osmolality - true hyponatremia
If plasma sodium is low and plasma osmolality is normal, what is this phenomena called?
Pseudohyponatremia
How is hyperglycaemia related to hyponatremia
High glucose can draw water into the cells, this dilutes sodium concentration - causing hyponatremia
What is true hyponatremia
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
Enzymes involved in steroidogenesis:
- Cytochrome P450 - contains a haem group to activate oxygen for oxidation reactions
- Steroid dehydrogenase - for alcohol/ketone/aldehyde interconversions and oxidation/reduction
Steroids proceed by the adrenal cortex
Cortisol (GC)
Corticosterone (GC+MC activity)
Aldosterone (MC)
Dehydroepiandrosterone (DHEA) - inactive androgen
What is the rate limiting step in steroidogenesis?
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
What does DHEA synthesis require?
Lyase activity of P450 17-alpha
What is the most common enzyme deficiency in congenital adrenal hyperplasia?
P450 21
Causes of hyperprolactinaemia
Physiological - stress, pregnancy, lactation, suckling
Pharmacological - dopamine receptor blockade, depletion of dopamine
Pathological - HP disorders, hypothyroidism, renal failure, seizures
What initiates secretion of prolactin?
Release of dopamine = inhibitory (causes release of prolactin) during Sleep, after meals, exercise and stress
What can cause spikes in growth hormone?
- 3 hours after eating
- after exercise
- 90mins after onset of sleep
- peak during deep REM sleep
Metabolic actions of GH
- increases lipolysis and lipid oxidation
- increases hepatic glucose production
- increases protein synthesis
- phosphate, sodium and water retention
Changes associated with acromegaly
Glucose intolerance
Hypercalcuria and hypercalcemia
What causes the hyperkalemia and hyponatremia in adisons disease?
Mineralocorticoid/aldosterone deficiency = salt wasting and reduced potassium excretion
What is diabetes insidious?
Relative or absolute lack of ADH resulting in inability to concentrate urine - polyuria, nocturia and polydypsia
Thyroid tests
TSH Free T4 Free T3 Thyroid antibodies - anti-TPO, Anti-TG TSH receptor antibodies
How to investigate hyponatremia
Blood gas sodium
Plasma osmolality
Urine Na and osmolality
Patient’s volume status
True hyponatremia
Decreased plasma osmolality caused by water gain or sodium loss
What is pseudohyponatremia?
Falsely low sodium rest caused by hyperlipidaemia or hyperproteinaemia
Causes of true hyponatremia when urine Na+ <20mmol/L (non-renal)
Increase in volume - CCF, hypoalbuminaemia
N volume - polydypsia
Reduced volume - vomiting, diarrhoea, XS sweating
Causes of true hyponatremia when urine Na+ >20mmol/L
Increase in volume - CRF
N volume - SIADH, hypothyroid, hypocorticolism
Reduced volume - diuretics, Addison’s, RTA, nephritis
How does pH affect calcium?
Alkalosis reduces ionised calcium and increases bound calcium
Acidosis increased ionised calcium and reduces bound calcium
What converts androstenedione to testosterone
17-beta-hydroxysteroid dehydrogenase
What converts pregnenolone to progesterone
3-beta-hydroxysteroid dehydrogenase
3 mitochondrial/ cytochrome P450 oxidation reactions involved in steroidogenesis
CYP11A1 - side chain cleavage
CYP11B1 - 11B hydroxylation
CYP11B2 - 18-hydroxylation
3 microsomal oxidation reactions involving CYP450 involved in steroidogenesis
CYP17A1 = P450 17α (17-hydroxylase/lyase)
CYP21A2 = P450 21 (21-hydroxylation)
CYP19A1 = P450 aromatase (little in adrenal)
Most common deficiency in congenital adrenal hyperplasia
P450 21 (CYP21A2)
Causes of hyperprolactinaemia
Physiological: stress, pregnancy, lactation, suckling
Pharm: dopamine receptor blockade ro depletion of dopamine
Path: prolactinoma, stalk compression, hypothyroidism, renal failure, seizures
How would you treat macroprolactinoma?
Dopamine agonist - cabergoline
Where is GH synthesised?
Somatotropic (acidophilic) cells of the adenohypophysis
Biochemical changes associated with acromegaly
Glucose intolerance
Hypercalcuria/calcemia
Screening test for cushion’s syndrome
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
Hyponatremia and hyperkalemia in addison’s disease
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
Grave’s specific features in addition to hyperthyroid features
- ophthalmology
- pre tibial myxoedema
Causes of pseudohyponatremia in normal osmolality
Hyperlipidemia or hyperproteinemia
Hyponatremia and hyperglycemia
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
Clinical features of hyponatremia
N+V, headache, confusion, lethargy, fatigue, appetite loss, irritable, muscle weakness, LOC, seizures
Non renal causes of true hyponatremia (<20mmol Na in urine)
↑volume - CCF, hypoalbuminaemia,
N volume - polydipsia,
↓ volume - vomiting, diarrhoea, excessive sweating
Renal causes of true hyponatremia (>20mmol Na)
↑volume - CRF
N volume - SIADH, hypothyroid, hypocortisolism
↓ volume - diuretics, Addison’s, RTA, nephritis
Diagnostic criteria for SIADH
Low plasma Na and osmolality Inappropriately high urine osmolality Urine Na >20mmol/kg Euvolaemia Normal renal, thyroid and adrenal function Not on diuretics
Results in a person using a thiazide diuretic
Low sodium and potassium
High HCO3-
Plasma investigation results in rhabdomylosis
High potassium
High U + C
V high creatine kinase
How does pH affect binding of calcium to proteins in serum
Alkalosis →
↓ ionised calcium
↑ bound calcium
Acidosis →
↑ ionised calcium
↓ bound calcium
K-EDTA, potassium and calcium plasma concentration results
K-EDTA binds K and shows high potassium, EDTA also chelates calcium which shows as low calcium
Causes of respiratory acidosis
Thoracic disease
NM disease
CNS depression
Causes of metabolic alkalosis
Antacids
Diuretics
Liquorice
Endocrine - cushion’s, CAH
Causes of respiratory alkalosis
Central stimulation: anxiety, pregnancy, hypoxemia, infection, trauma
Pulmonary: embolism, acute pulmonary deem, asthma, pneumonia
Causes of metabolic acidosis
Increased anion gap
Methanol, uraemia, DKA, glycols, iron, lactic acidosis,
Normal anion gap
Diarrhoea, RTA, Addisons,
