23-02-23 - Control of reabsorption and secretion in the nephron Flashcards
Learning outcomes
How does transporter in the Proximal Tubule and Loop of Henle occur?
How does a majority of transport from the distal tubule onwards take place?
- Transport in Proximal Tubule and Loop of Henle is both paracellular and transcellular
- Majority of transport in from Distal Tubule onwards is transcellular only
How does transporter in the Proximal Tubule and Loop of Henle occur?
How does a majority of transport from the distal tubule onwards take place?
- Transport in Proximal Tubule and Loop of Henle is both paracellular and transcellular
- Majority of transport in from Distal Tubule onwards is transcellular only
Obligatory reabsorption in the proximal tubule. Substances reabsorbed in the proximal tubule:
* 100% (3)
* 90% (2)
* 80% (2)
* 65% (3)
* 50% (1)
* 35% (1)
Where does regulated reabsorption/secretion occur?
- Obligatory reabsorption in the proximal tubule
- Substances reabsorbed in the proximal tubule:
- 100% (3) - glucose, amino acids, proteins
- 90% (2) - phosphate, sulphate
- 80% (2) - potassium, filtered bicarbonate
- 65% (3) - water and sodium, calcium
- 50% (1) - chloride
- 35% (1) - magnesium
- Regulated reabsorption/secretion occurs later in the tubule
What kind of substances are secreted in the proximal tubule?
What else can happen to these products?
How is rapid secretion in the proximal tubule enabled?
Why can rapid clearance of drugs prove problematic?
- End-products of metabolism e.g. organic acids and bases (Bile salts, oxalate, urate, catecholamines), need to be rapidly removed from the body through secretion into the proximal tubule
- Toxins and drugs are also secreted into the PT for excretion
- Some of these end-products of metabolism can also be filtered at the glomerulus
- No reabsorption along tubules, enabling rapid excretion
- Rapid clearance can prove challenging for maintaining therapeutically effective drug concentration e.g. penicillin, which piggy-back on promiscuous transporters
What is the thin descending limb of the LOH lined with?
What does this enable?
What is the thin ascending limb impermeable to?
What is it permeable to?
What is the thick ascending limb lined by?
What 4 substances can be reabsorbed in the thick ascending limb?
What is the thick ascending limb impermeable to?
- The thin descending limb of the LOH is lined by simple, shallow epithelial cells
- This enables easy movement of H2O via Aquaporin 1 channels (AQP1)
- The thin ascending limb is impermeable to H2O
- Permeable to Na+ and Cl- which move via paracellular route
- The thick ascending limb is lined by epithelial cells, which have a has very high metabolic activity (a lot of ATPases needed for secondary active transport)
- 4 substances can be reabsorbed in the thick ascending limb:
1) Na+
2) Cl-
3) Mg2+
4) Ca2+ - The thick ascending limb is impermeable to H2O
How does most of the transport of ions/H2O occur in the distal convoluted tubule (DCT).
What happens to tight junctions here?
How does Na+ and Cl- transport occur here?
How does Ca2+ and Mg2+ transport occur here?
- Transport of most ions / H2O from the distal convoluted tubule onwards is transcellular
- In the DTC, tight junctions are tight
- In the DCT:
- There is apical transcellular movement of Na+ and Cl- into the DCT cell via NCC (co-transporter)
- There is basolateral movement of Na+ and Cl- out of the DCT cell via channels
- There is apical transcellular movement of Ca2+ and Mg2+ into the DCT cell via channels (e.g TPRV45 and TRPM5)
- There is basolateral transcellular movement of Ca2+ and Mg2+ out of the DCT cell via exchangers (Na+ and Mg2+/Ca2+ exchangers) and Ca2+ ATPases
Reabsorption/secretion in the Connecting tubule (CNT)/Cortical collecting duct (CCD)
What is this the only portion of the nephron to have?
What are the 2 cells types in the CNT/CCD?
What do many hormones target here? Why is this?
- Reabsorption/secretion in the Connecting tubule (CNT)/Cortical collecting duct (CCD)
- The CNT and CCD are the only pat of the nephron with 2 types of cells
- 2 cells types in the CNT/CCD:
1) Principal cells (Na+ absorbing) which predominate (70% of cells)
* Secrete K+ here (K+-sparing diuretics target Na+ here)
2) Intercalated cells (acid/base)
* 30% of cells
* Energised by H+/K+- ATPase
* Type A, type B, non A-non B
* Many hormones target principal cells as this is where the “finetuning” of Na+ balance takes place
Reabsorption/secretion in the Medullary collecting duct (MCD).
What is the MCD the final site of?
What does this area determine?
What does MCD H2O permeability depend on?
What 2 other substances is there some permeability to in the MCD?
What is the MCD also permeable to?
What does reabsorption of Urea in the MCD contribute to?
What can also be secreted in the MCD?
What is this used for?
- Reabsorption/secretion in the Medullary collecting duct (MCD)
- The MCD is the final site for processing urine
- The MCD determines the final urine output of water and solutes
- Permeability of MCD to H2O is dependent on AVP
- There is some permeability to Na+ and Cl- in the MCD
- The MCD is also permeable to urea (unlike CCD)
- Reabsorption of urea in the MCD contributes to raising osmolality of the medullary interstitium
- The MCD can also secrete H+ here, so plays a key role in regulating acid-base balance
Where in the nephron is very important location for maintaining K+ balance?
- CNT/CCD is a very important tubular location for maintaining K+ balance, with a lot of it being secreted
What are 4 hormones that regulate tubular transport?
- 4 hormones that regulate tubular transport:
1) Arginine vasopressin (AVP aka ADH)
2) Angiotensin 2 (AngII)
3) Aldosterone
4) Atrial natriuretic hormone (ANP)
What is the value for normal plasma osmolality?
How precisely is it regulated?
At what difference in osmolality will osmolality regulating mechanisms start to operate?
What is plasma osmolality detected by?
How does this work?
What is the half-life of AVP?
Where can water reabsorption occur in the nephron with AVP?
How does this happen?
- Normal plasma osmolality is 280-290 mOsm/kg H2O
- It is regulated very precisely
- Differences in either direction of ~3 mOsm/kg H2O results in the operation of the body’s osmolality regulating mechanisms
- Plasma osmolality is detected by osmoreceptors in the brain (Circumventricular organs)
- They signal secretion of arginine vasopressin (AVP aka ADH) from the posterior pituitary gland, preventing diuresis (water loss)
- AVP has a very short half-life (10-15min)
- Water reabsorption can occur in the Cortical collecting duct (CCD) and Medullary collecting duct (MCD) when AVP is present
- AVP increases H2O permeability in all nephron segments beyond the distal convoluted tubule
Where are AVP receptors located? How does AVP get here?
What type of receptor is V2R?
Describe the 5 steps in the action of the V2R receptor?
- Vasopressin receptors V2R are located on the basolateral membrane of CD (collecting duct) principal cells
- AVP arrives in bloodstream, diffuses into interstitium and binds V2Rs
- V2R is a G-protein coupled receptor Gs
- 5 Steps in the action of the V2R receptor:
1) When activated by ADH, the V2R receptor stimulates adenylyl cyclase, increasing [cAMP]i
2) cAMP activates protein kinase A
3) Protein kinase A phosphorylates the intracellular pool of AQP2 channels
4) Phosphorylation results in trafficking to the apical membrane
5) Resulting in more H2O being reabsorbed back to plasma, reducing its osmolality
Describe the RAAS system (in picture).
What is the rate-limiting enzyme in the RAAS system?
What 3 events is renin release stimulated by?
- RAAS system (in picture)
- Renin is the rate-limiting enzyme in the RAAS cascade
- 3 events renin release is stimulated by:
1) Decreased tension in the afferent arterioles (decreased renal perfusion pressure)
2) Increased renal sympathetic nerve activity (triggered by baroceptor reflex)
3) Decreased delivery of NaCl to the macula densa
What receptors does angiotensin II act on?
What are 3 effects does angiotensin II have on the renal tubules of the kidney?
- Angiotensin 2 acts on AT1 receptors in the:
1) Vascular smooth muscle cells of blood vessels
2) Hypothalamus
3) Renal tubules of the kidney
4) Zona glomerulosa of adrenal glands - 3 effects angiotensin II has on the renal tubules of the kidney:
1) Increased secretion of aldosterone from adrenal glands
2) Increased Na+ reabsorption in the kidney
3) Increased extracellular volume (ECV)