What factors control renin secretion?
- Intrarenal baroreceptors in the afferent arteriole (low BP)
- Sympathetic nerve endings on tunica externa
- Sodium content of the proximal and distal convoluted tubule detected by the macula densa - local hormone released is prostaglandin to signal low glomerular pressure to the juxtaglomerular cells
What is renin?
Renin is a PROTEASE produced in the kidney to increase blood pressure.
Its main function is to convert angiotensinogen to angiotensin 1. Angiotensinogen is produced in the liver and secreted into plasma.
Where is renin produced?
Renin comes from the nephron, particularly the juxtaglomerual apparatus.
The nephron has two places that secrete renin:
- Juxtaglomerular cells in the TUNICA MEDIA of afferent arterioles
- Lacis cells between afferent and efferent arterioles
What factors INCREASE renin production?
- Decreases in ECF
- Decrease in BP - upright posture, cirrhosis, renal artery stenosis
- Increase in sympathetics
- Increase in prostaglandins
What factors INHIBIT renin production?
- Increased concentration and absorption of sodium and chloride ions in the macula dense (DCT)
- Increased afferent arteriole pressure
- Angiotensin II via negative feedback loop
- Vasopressin
Where does the majority of renal absorption take place?
Proximal convoluted tubule, 65%, including potassium.
Where does aldosterone act to increase sodium absorption?
Salivary glands
Sweat glands
Collecting duct
Small intestine
What are the effects of angiotensin II OUTSIDE the kidney?
- Smooth muscle constrictor in vessels
- Causes increased aldonsterone release from the adrenal glands
- Causes increased ACTH release from the pituitary gland
- Causes release of noradrenaline from sympathetic neurons which go on to increase renin secretion!
- Works outside the blood-brain barrier on two areas:
- Area postrema to potentiate vasopressin effect
- Subfornical organ and organum vasculosum to increase thirst! and thus water intake
What are the effects of angiotensin II within the kidney?
- Increase sodium absorption directly
- Arteriolar constriction on both afferent and efferent arterioles, efferent more so to decrease GFR and increase sodium re-absorption
- Mesangial constriction to decrease GFR further
How is urea absorbed in the kidney?
Urea is passively absorbed from the collecting ducts
How is glucose absorbed in the kidney?
Glucose is removed by active absorption in the proximal convoluted tubule 100%.
How is the concentration of protein affected in the afferent vs efferent arteriole?
The protein concentration in the efferent arteriole is higher because there is less solvent.
How does water work as a diuretic?
Inhibits vasopressin secretion
How does ETOH work as a diuretic?
Inhibits vasopressin secretion
How does glucose / mannitol work as a diuretic?
Produces osmotic effect causing diuresis
How to xanthines (caffeine, theophylline) work as diuretics?
Decrease renal absorption of sodium and increase GFR
How do LOOP diuretics work?
Inhibit the sodium-potassium-chloride-2 cotransporter in the THICK ASCENDING LOOP
How to thiazide diuretics work?
Inhibit the NaCl cotransporter in the distal convoluted tubule
How to potassium sparing diuretics work?
They inhibit sodium and potassium exschange in the collecting duct by blocking the effect of aldosterone or epithelial sodium channels
How do carbonic anhydrase inhibitors work as diuretics?
e.g. acetazolamide
Decrease the secretion of protons with resultant increased sodium and potassium excretion
They also inhibit bicarb reabsorption in the tubules
Where are the most protons secreted in the nephron?
Proximal convoluted tubule via the sodium/hydrogen countertransporter. However, the concentration gradient that is achieved cannot cause acidosis greater than 6.9
Which ions are absorbed in the PCT?
- Sodium: Na/H symporter so high amounts of H+ are secreted here in exchange for sodium
- Potassium 65% absorbed here by active (mostly) and passive
- Glucose, however much glucose goes in in absorbed by the SGLT transporter then into the capillaries via the GLUT 2 uniporter. This is limited to 10-12mmol/L, in excess of this amount is unable to filtered out
- Chloride/HCO3 exchanger
- Amino acids: 99% of aas are absorbed here in conjunction with sodium
- Urea: 50% absorbed here by diffusion, the mechanism for this is that most water reenters insterstitium via aquaporin I. This concentration gradient facilitates urea diffusion
- Bicarb via chloride transporter, 85% absorbed here
- Phosphorus: 90% here, inhibited by PTH
What is mainly secreted in the PCT?
- Protons, in exchange for sodium
- Every H+ in the lumen will bind to bicarb present there to form H2O and CO2 (Hasselbach’s equation)
- For every H+ returning into the interstitium, one more bicarb is generated
- This bicarb is then returned to plasma and then acts as if HCO3 is absorbed
- So overall, one proton secreted for every sodium absorbed and bicarb comes in too
What happens to protons that are secreted into the renal lumen?
- Bind with bicarb to form carbonic acid, a weak acid which quickly dissociates to H2O and CO2, low pK 6.1
- Bind with hydrogen phosphate (HPO4) to form dihydrogen phosphate (pK 6.8) which occurs mainly in the DCT and CD where phosphate concentration is highest
- Bind with NH3 to form NH4+ (pK 9) which is highest concentration in the DCT
