Renal physiology Flashcards
Proximal tubule
Site of bulk reabsorption
- 2/3 of sodium reabsorbed
- all glucose and amino acids reabsorbed
- Site of bicarbonate reabsorption
Site of carbonic anhydrase activity
Site of major secretion
- anions - urate, ketoacids, penicillins, diuretics, cephalosporins, radiocontrast media
- cations - creatinine, lithium, cimetidine
Countercurrent multiplier system
Site of urinary concentration
- after bulk water and solute reabsorption, osmotic fluid enters the thick and thin descending limbs before looping back up into the thick and thin ascending limbs
- 20-30% sodium reabsorbed into the interstitium in the thin andk thick ascending limb without water following and creates a highly osmotic renal medulla via active transport
- The NaKCl channel on the apical membrane acts to move Na and Cl into a concentrated interstitium
- This is the site of action of loop diuretics
Thick ascending limb and magnesium
- Ca2+ and Mg2+ are reaborbed in the thick ascending limb via paracellular pathways via secondary active transport
- Frusemide disrupts the gradient required for this to occur, thus contributing to hypomagnesaemia
- The claudin-16 protein is the protein channel responsible for magnesium transport, thus mutations will cause congenital reductions in magnesium, and nephrocalcinosis
Bartter’s syndrome
Autosomal recessive disorder resulting in chronic normotensive hypokalaemic metabolic alkalosis
Due to disruption of the NaK2Cl protein on the thick ascending limb, similar to frusemide effect
Hypomagnesaemia and hypercalciuria develop
Prostaglandin E levels in urine are high, specific to condition
5 subtypes, types IV and V associated with neonatal deafness
Distal convoluted tubule
Responsible for water and sodium reabsorption
Site of thiazide activity, blocking the NKCC1 molecule on the apical membrane which enables active reabsorption of sodium and chloride
Like frusemide, thiazide and indapamide also result in hypomagnesaemia as absorption occurring here requires the electrostatic gradient from NKCC1 activity
Hypocalciuria occurs at this site due to thiazide activity
Magnesium reabsorption
Occurs in the distal convoluted tubule via the TRPM6/7 transporter channels
2-5% absorbed here, fine tuning occurs
- Tacrolimus inhibits the TRPM6/7 channel
- EGF also has some role inhibiting magnesium reabsorption
Causes of hypomagnesaemia
GI losses
Decreased intake
Drugs
- Diuretics
- Tacrolimus, amphotericin
Hypokalaemia
Genetic disorders TRPM6 mutation
Redistribution in the intra and extracellular space
Gitelmann’s syndrome
Autosomal recessive disorder due to loss of function of the NCCT NaCl transporter on distal convoluted tubule
Similar effect as thiazide diuretic inhibition
Causes chronic normotensive, metabolic alkalosis, hypokalaemia, hypomagnesaemia, and hypocalciuria
Increased renin and angiotensin
Normal renal prostaglandin E
May be diagnosed late childhood or early adulthood and presents as electrolyte related myopathy
Pseudohypoaldosteronism type 2
Rare autosomal dominant disorder, presents as early onset hypertension
Associated narrow anion gap metabolic acidosis, hypercalciuria, hyperkalaemia
Associated raised aldosterone levels
Treatment with thiazide diuretics; its effects oppose thiazide use
The principal cell on the cortical collecting duct
Acts to reabsorb water and sodium
Water reabsorption is ADH mediated and promotes aquaporin protein expression on the apical and basolateral membranes; occurs via G protein coupled receptors
Aldosterone acts on cells to increase the expression of ENaC proteins and on the apical membrane and NaK ATPases on the basolateral membrane to increase sodium reabsorption
Lithium is also reabsorbed here
BNP acts to down regulate ENaC expression
Potassium sparing diuretics
Amiloride and Triameterene (and high dose trimethoprim)
- Direct sodium channel closure
- Amiloride can block Li reabsorption
Spironolactone and eplerenone
- Competitively antagonises aldosterone at recepto
- Eplerenone - less anti-testosterone effects
Aldosterone independent hypertensive syndromes
(inherited tubular disorders)
17 alphahydroxylase and 11beta hydroxylase deficiencies
Excess liquorice ingestion (blocks cortisol breakdown into cortisol)
Liddle’s syndrome
Liddle syndrome
Chromosome 16, autosomal dominant disorder
Hypertensive hypokalaemic metabolic alkalosis
low plasma renin and aldosterone levels
Increased number of Na channels
Mutation identified on beta or gamma subunit of Na channel
Presentation similar to apparent mineralocorticoid excess
Amiloride and triamterene used for treatment
Potassium handling in the body
Potassium controlled primarily by kidney, re-absorbed in PCT and LOH
Fine tuning via aldosterone in DCT principal and intercalated cells
Gut control - meal increase potassium secretion
Also controlled by central circadian rhythm
Urinary potassium <20, FExK <3%
Potassium excretion is also enhanced by increased sodium and water to the distal tubule
