Formation of urine 2 Flashcards
Descending limb of the Loop of Henle
This part is very permeable for water- allows extraction of water into blood.
Features:
- Thin walls
- No proteins to actively transport ions
- Walls packed with aquaporins.
- Some tight junctions for water movement.
Ascending limb of the Loop of Henle
This part is very impermeable to water and permeable to Na+ and Cl-.
- Water can be secreted but not absorbed.
Features:
- Thick walls
- NKCC2 co-transporters to absorb Na+, K+ and Cl-
Solute transport in the ascending loop of Henle
The apical membrane of the tubular cells contain NKCC2 co-transporter.
- Na+, K+ and 2Cl- transporter into cells.
Na+ and Cl- secreted into the medulla draws water out in the ascending limb into the blood.
Na+ and K+ repels Ca2+ and Mg2+ due to the positive charge.
Inhibition of NKCC2 co-transporter
Inhibited by furosemide and other loop diuretics.
Prevents Na+ and Cl+ absorption so water is not drawn out.
The keeps water, Na+ and Cl- in tubules- promoting natriuresis.
Osmolarity changes in the Loop of Henle
Fluid entering the loop of Henle is isotonic.
The deeper down the descending limb, the more hypertonic the tubular fluid becomes.
- Due to the absorption of water and retention of Na+ and Cl-.
Moving through the ascending limb, the tubular fluid becomes more hypotonic:
- Na+ and Cl- actively reabsorbed.
- Water retained
Countercurrent multiplication
Large osmotic gradient is created within medulla which creates deep concentration gradients for filtrates.
Caused by NKCC co-transporter in ascending limb of the Loop of Henle.
Urea also diffuses from the collecting duct to make the medulla more hypertonic at the loop of Henle- draws out more water
Main processes in the Distal tubule
Na+ and Cl- actively reabsorbed.
K+ and H+ secreted into tubular fluid in exchange for other ions.
Na+ and Cl- reabsorption in DT
Actively reabsorbed by exchanging with K+.
- Na+ and Cl- co-transported into cell
- Cl- leaves cell via channel basolaterally.
- Na+ leaves cell via sodium-potassium pump
Na+ exchange occurs in the late DT and early CD at principal cells.
Principal cells
Cell of the DT that is sensitive to aldosterone.
K+ is secreted in exchange for Na+ at the basolateral membrane.
- K+ secreted into lumen via channel
- Na+ enters cell via channel
- Exchanged at basolateral membrane
RAAS activated Na+ reabsorption at DT
Macula densa senses low Na+ at DT.
- Signals to juxtaglomerular cells to release renin.
Renin causes eventually secreted of angiotensin II= increased aldosterone.
Aldosterone increases Na+ reabsorption/ K+ secretion at DT.
- This inhibits juxtaglomerular cells
- Increases water absorption and blood pressure
Intercalated cells
- Location
- Different types
Cells located in the DT and early collecting cells
- Acid/base regulation
Exchanges Na+ for H+.
Alpha cells:
- H+ secreted in exchange for K+ or Na+.
- H+ secreted via H+ ATPase
- Reabsorbs HCO3-
Beta cells:
- Secrete HCO3- via pendrin
- Reabsorbs H+
Alpha intercalated cells
Cells located in early CD and DT.
Secretes H+ via:
- Exchange with K+
- Exchange with Na+
- H+ ATPase
Reabsorbs:
HCO3-
Beta intercalated cells
Cells located in early CD and DT.
Secretes:
-Bicarbonate through pendrin (exchanged with Cl-)
Absorbs:
H+
ADH - Secretion location - Half life - Metabolism -
Anti-diuretic hormone / Vasopressin.
- Regulates water balance
Secreted from posterior pituitary gland after stimulation from the hypothalamus.
Short half life- 10-15mins
Metabolised in the liver and kidneys
ADH mechanism
Acts on vasopressin 2 receptors (V2)
- Receptors are on basal membrane of DT principal cells.
Activation of V2 activates Aquaporin channels on apical membrane.
- Uses G-protein cell signaling to increase intercellular cAMP.
Allows water to move into blood
Maximal circulating ADH.
ADH highest levels in the blood when severely dehydrated.
Causes CD to be very permeable to water due to maximal insertion of aquaporin 2 channels.
Can only reabsorb up to 66% of water entering the collecting duct.
Can cause urine to be reduced to 300mL a day.
No circulating ADH
Causes CD to be impermeable to water- no Aquaporin-2 channels
Causes large volume of water to be excreted in urine- up to 30L a day.
Diabetes insipidus
Type of diabetes caused by lack of ADH
Causes CD to be impermeable to water—> large volume of urine (up to 30L a day)
Treated with synthetic ADH
Two types:
Nephrogenic
Neurogenic
Nephrogenic diabetes insipidus
CD impermeability due to the CD not responding to ADH normally.
Treated:
- Chlortalidone diuretic
- Indometacin (anti-inflammatory)
Neurogenic diabetes insipidus
CD becomes impermeable to water due to lack of ADH production in the brain.
Treated:
- Desmopressin
- Vasopressin
- Carbamazepine
SIADH
Syndrome of inappropriate ADH
Excessive release of ADH for many reasons:
- Head injury
- Ecstasy side effects
Can cause hyponatremia and possible fluid overload
Treatment
- ADH inhibitors
Substances that increase ADH secretion
Nicotine
Ether
Morphine
Barbiturates
Agents that inhibit ADH secretion
Alcohol- acts as a diuretic
