Renal Physiology Flashcards
Points on creatinine
Serum creatinine - from metabolism of creatine in skeletal muscle and dietary meat intake, varies depending on age, sex, body size, freely filtered across glomeruli and not reabsorbed - also secreted by proximal tubules
Limitations of creatinine clearance
Exceeds true GFR x 10-20% due to tubular secretion
Secretion increases with drop in GFR
% components body water, ECF, ICF
- Body water - 60%, lower in high BMI due to fat and loss of muscle mass
- ECF - 33%
- Main cation - sodium
- Main anion - chloride and bicarbonate
- ICF - 66%
- Main cation - potassium
- Main anion - oganic phosphates
Measurement of plasma osmolality and how it is regulated
- Plasma osmolality in mmol = (2xNa) + glucose + urea
- Small contributions from glucose and urea except in cases of uncontrolled DM and reduced renal function
- Regulation: via osmoregulators/ADH in hypothalamus -> regulate water intake/excretion, increase thirst and release of ADH, extremely sensitive and plasma osmolality tightly controlled
Place of action of diuretics
- Acetozolamode → proximal convoluted tubule
- Loop diuretics → thick ascending loop of henle
- Thiazides → distal tubule
- Potassium sparing diuretics → collecting tubule principal cells → inhibit reabsorption of sodium and excretion of potassium
Response to increase in plasma osmolality
Detected by osmoreceptors in the hypothalamus
- Stimulates increase water intake by thirst
- Stimulates neurohypophysis of posterior pituitary to secrete ADH
MOA ADH
- Binds to V2 receptors in nephron (thick ascending limb -> collecting ducts) - Release of AQP2
- Chronic stimulation ADH → increased phosphorylation AQP2 → binds to tubular membranes allowing free entry of water into cell
- Short term stimulation → release of preformed vesicles of AQP2
- Water then leaves cell via basolateral membrane via AQP3 and AQP4
- Once stimulation ceased - AQP2 returns to cells
What is the role of ADH
- Maintain plasma osmolality - via V2 receptor, mutation in receptor → nephrogenic diabetes insipidus
- Volume regulator - when fall in arterial blood volume → fall in systemic BP → increase ADH - water retention via V2, increased vascular resistance via V1 receptors
Notes on Tolvaptan
- Blocks V2 receptors in distal nephron and collecting duct
- Prevents binding of vasopressin → reduces expression of aquaporins
- Promotes water excretion → polyuria and potential dehydration
- Important to maintain adequate hydration to prevent activation of V1 receptors
- PCKD → reduces cyst formation
Features of SIADH
- Euvolaemic hypotonic hyponatraemia → low serum sodium, low plasma osmolality, high urine osmolality (> 100), normally also high urine sodium and normal serum potassium and pH
Causes of SIADH
- Ectopic secretion of ADH - small cell lung carcinoma (most common tumour)
- Any CNS disorder
- Drugs - carbamazepine, SSRI, chemo, immunosupressants, ciprofloxacin, amiodarone, ecstasy
- Any recent surgery (mediated via pain afferents)
- Pulmonary disease
- Hormone deficient - hypopituitarism and low TSH
- Idiopathic - normally due to occult tumour or GCA
Causes of euvolaemic hypotonic hyponatraemia
- Excessive water ingestion normally secondary to psychiatric illness → kidneys able to excrete up to 10L/day
- Low dietary solute intake but high fluid intake - alcoholics, tea and toast diet
- Advanced renal failure - increased solute excretion but impaired water excretion despite normal levels of ADH
- Thiazide diuretics - often patients euvolaemic, reduction in diluting ability of kidney
Causes of hypovolaemic, hypotonic hyponatraemia
- Renal fluid losses secondary to excessive diuretics - high urine sodium and chloride
- GI losses such as diarrhoea or 2rd spacing → low urine sodium
- GI losses due to vomiting → high urine sodium in severe metabolic alkalosis - sodium excretion with loss of urinary bicarbonate, low urine chloride
Causes of hypervolaemic hypotonic hyponatraemia
- Increase in ECF colume
- Lack of cardiac output in heart failure
- Reduced tissue perfusion → activation of ADH secretion → water retention → oedema
- Arterial vasodilatation → cirrhosis
Causes of hypertonic hyponatraemia
- Hyperglycaemia → increase in serum osmolality → water drawn from cells → expands ECF and lowers serum Na concentration
- IVIG → hyperteonic solution
- Sorbitol or mannitol irrigation in urological or gynaecological procedures → expansion of ECF