Renal - Physiology Flashcards
What are the three ways the GFR autoregulates?
1) autonomic vasoreactive (myogenic) reflex in afferent arteriole
2) tubuloglomerular feedback:
- reflex vasoconstriction or dilation of AFFERENT arteriole
- mediated by macula densa in thick ascending loop of henle:
Increased GFR –> increased solute delivery to macula densa–> vasoconstriction of afferent arteriole –> decreased GFR
3) angiotensin II mediated vasoconstriction of efferent arteriole
Increased GFR results in increased solutes delivered to what?
(In the tubuloglomerular feedback mechanism)
To the macula densa
In the tubuloglomerular feedback model, when increased solutes are delivered to the MACULA DENSA what happens?
Vasoconstriction of the AFFERENT arteriole
–> decreased GFR
In autoregulation of GFR angiotensin II does what?
Angiotensin II mediated VASOCONSTRICTION of EFFERENT arteriole
When there is decreased GFR how does that increase angiotensin II
Decreased GFR results in Renin produced by granular cells in afferent arteriole at Juxtaglomerular apparatus
Renin then catalyses angiotensinogen to angiotensin I
Angiotensin I is converted to angiotensin II by ACE
Where is renin produced and in response to what?
Renin is produced by granular cells in AFFERENT arteriole in juxtaglomerular apparatus
In response to decreased Renal blood flow
What does renin do?
Catalyses conversion of angiotensinogen to angiotensin I
In the PROXIMAL TUBULE is NaCl reabsorbed?
60% of NaCl resorption is in PROXIMAL TUBULE
In PROXIMAL TUBULE
Where is water resabsorped?
Through tight junctions driven by oncotic pressures and hydrostatic pressure
Also ACTIVE CHANNELS aquaporin-1
In the PROXIMAL TUBULE
How is Na absorbed?
Basolateral 3Na/2K-ATPase keeps a gradient
On APICAL SIDE: Na-H+ exchanger Symporter with phosphate Symporter with glucose Symporter with amino acids
In the PROXIMAL TUBULE
How is Cl absorbed?
Early in the tubule it isn’t absorbed
Because when Cl is left in the lumen it then enables removal of HCO3- from the lumen early on (pushing it to be converted to H20 and CO2)
But later:
APICAL side:
Cl/formate exchanger
BASOLATERAL:
K/Cl symporter
In the PROXIMAL TUBULE what happens to the Formate that gets secreted in exchange for Cl absorption?
Formate binds to H+ and forms formic acid which is reabsorbed by passive diffusion
In the PROXIMAL TUBULE:
How is bicarbonate reabsorbed?
H+ is in the lumen from Secretion by the H+/Na+ exchanger
HCO3- then binds to H+to form carbonic acid H2CO3
Carbonic acid in the lumen is converted by CARBONIC ANHYDRASE to H20 and CO2. The CO2 then diffuses passively into the cell.
Inside the cell CARBONIC ANHYDRASE reforms H2CO3 which dissociates to H+ and HCO3-.
HCO3- then exits via APICAL Na/HCO3- symporter
Once Bicarbonate is absorbed into the cell in the PROXIMAL TUBULE how does it exit the cell?
Via the Na/HCO3- symporter
Where does acetazolamide act?
Inhibits carbonic ANHYDRASE at the proximal tubule
Therefore blocks bicarbonate reabsorption
Therefore acetazolamide alkanylises the urine
In the PROXIMAL TUBULE what happens to ammonia?
Secretion
glutamine breaks down to form NH3 which diffuses out of the cell and in the lumen combines with H+ to become NH4+
In the cell some NH3 combines with H+ to become NH4+ which gets EXCHANGED with Na to be secreted into the lumen
What is the effect of a high K+ on ammonia in the PROXIMAL TUBULE
Because in the cell there is high K+ there is reduced NH+ creations (high intracellular K+ such as in HYPERALDOSTERONISM reduces ammoniogenesis)
That is why hyperaldosteronism creates Renal Tubular Acidosis Type IV
In the PROXIMAL TUBULE what happens to phosphate?
Filtered phosphate ion (PO4-) in the lumen combines with H+ (secreted by Na/H+ exchanger) to form H2PO4
Phosphate also cotransports with with Na (and this cotransporter is regulated by PTH
How is glucose reabsorbed?
In the PROXIMAL TUBULE
Apical side has SGLT2 cotransporter that moves glucose with Na from lumen into the cell
Basal side has GLUT2 transporter to exit glucose from the cell into the blood
How are amino acids reabsorbed?
In the PROXIMAL TUBULE there are Multiple apical transporters specific for different amino groups, usually cotransporters with Na+
What happens if peptide hormones get filtered?
In the PROXIMAL TUBULE
Peptide hormones (ie insulin, growth hormone, beta2 microglobulin and albumin) absorbed by absorptive endocytosis then degraded by acidified endocytic lesions.
What happens to protein bound drugs not filtered but that need to be renally cleared?
In the PROXIMAL TUBULE protein bound drugs not filtered at glomerulus (ie penecillin / cephalosporins / salicylates / oseltamivir) are SECRETED
Probenecid inhibits this secretion so raises drug plasma concentration
How does Probenacid lower urate levels?
In the PROXIMAL TUBULE the organic anion transporter (OAT) reabsorbs uric acid from the lumen
If probenecid (an organic acid) is present, the OAT binds preferentially to it (instead of to uric acid), preventing reabsorption of the uric acid.
Lumen then retains more uric acid, lowering uric acid concentration in the plasma
Why does trimethoprim raise Cr?
In the PROXIMAL TUBULE there is cation secretion of organic cations including Creatinine, and amine neurotransmitters such as ACh, dopamine, adrenaline and noradrenaline
trimethoprim competes with these cation transporters and raise Cr levels but don’t impair GFR
In the PROXIMAL TUBULE which drugs are secreted by the ATP dependent p glycoprotein?
cyclopsorin
digoxin
Tacrolimus
What is the only thing that happens in the thin descending loop of henle?
highly water permeable via aquaporin-1
In the THICK ascending LOH how much NaCl is absorbed?
15-20% of NaCl
In the THICK ascending LOH how is Na absorbed?
via Apical Na/K/2Cl transporter
(This is where LOOP DIURETICS ACT)
- K+ is rate limiting substrate, but K+ also gets recycled via K+ channel
- Also can use NH4+ instead of K+
The Gradient for Na+ created by basolateral 3Na/2K exchange
In the THICK limb of LOH what happens to Mg?
Reabsorption via interstitial pathway driven by K+ recycling creating positive charge in lumen relative to interstitium
In the THICK ascending LOH what happens to calcium?
Calcium resorption via interstitial pathway driven by K+ recycling creating positive charge in lumen relative to interstitium
But also calcium-sensing G protein coupled receptor CaSR regulates the NaCl reabsorption (senses high calcium levels and inhibits reabsorption by stopping the recycling of K+)
How much of NaCl is reabsorbed in distal convoluted tubule?
5% of NaCl
How is water reabsorbed in DCT?
It isn’t. Impermeable to water
In the DCT how is sodium reabsorbed?
Absorbed on apical side by Na/Cl cotransporter
Encoded by NKCC1
(thiazide sensitive**)
Down gradient created by 3Na/2K-ATPase on basal membrane
In the DCT how is magnesium absorbed?
Reabsorption via channels (genes TRPM6 + TRPM7)
**tacrolimus inhibits TRPM
In the DCT how is calcium absorbed?
Apical Ca channels (TRPV5)
Basal 3Na+/Ca++ exchange
Which diuretics act in the DCT?
The thiazides, and thiazide-like diuretics (ie indapamide and metolazone)
They inhibit the apical Na/Cl transporter
Because of this they also increase the Ca reabsorption (because of more positive charge in lumen)
This results in hypocaciuria and so decreases calcium renal stones
In the collecting duct where are the principle cells located?
Cortical
How much NaCl is absorbed in the collecting duct and by which cell?
Cortical located Principal cells absorb 5% of NaCl
In the Cortical Duct Principal Cell how is Na absorbed?
Apical entry via amiloride-sensitive channels driven by gradient from basolateral 3Na/2K channels
The apical channels are called epithelial Na channels (ENaC)
Increased ENaC with aldosterone
In the collecting duct PRINCIPAL CELLS what happens to K+?
SECRETION!!
K+ secreted by apical K+ channel driven by K+ gradient from 3Na/2K-ATPase exchanger on basal surface
Also driven by negative energy of the lumen once Na been reabsorption
In the cortical collecting duct PRINCIPAL cells what would cause a DECREASES K+ secretion:
1) if fast tubular flow (ie volume expansion)
2) luminal nonreabsorbed anions (ie bicarb or penicillin)
3) decreased ENaC (ie trimethoprim / pentamidine)
Where does amiloride act?
Amiloride blocks sodium resorption by the ENaC channels on Principal Cells of Collecting Duct
How does lithium get reabsorbed?
Also comes through the ENaC channels in the cortical collecting duct Principal Cells
Will amiloride increase or decrease serum lithium levels?
Decrease because it blocks ENaC channels so lithium isn’t reabsorbed
What does BNP do in the cortical collecting duct?
In the principle Cells BNP binds to the basolateral surface and results in DECREASED ENaC activity, so results in less Na absorption
What happens in Type A Intercalated Cells of Collecting Duct?
acid secretion and bicarb reabsorption
On the APICAL side:
H+ gets SECRETED by a H+ pump
(** this is increased with aldosterone)
H+ also gets secreted in a H+/K+ exchanger
On the BASOLATERAL side:
Bicarbonate absorbs into blood via Cl/HCO3 exchanger
What happens in Type B Intercalated Cells of Collecting Duct?
bicarb secretion and acid reabsorption
- Type B: has the proton pump on basolateral side and exchanger on apical side
What electrolytes are reabsorbed in MEDULLARY collecting duct?
Na and K via Na channels and K channels in the apical membrane
Basolateral 3Na/2K exchanger channels drive the Na gradient
Where is urea reabsorbed?
Medullary collecting duct
What does aldosterone do in the kidney?
In the cortical medullary cell it INCREASES apical ENaC sodium absorption
In the cortical Type A intercalated Cells it INCREASES apical H+ secretion
What does atrial natriuretic peptide and renal natriuretic peptide (urodilatin) do?
Inhibits the apical Na channels in medullary collecting duct
How does Vasopresson (ADH) act in the Collecting Duct?
In the collecting duct on the BASOLATERAL membrane there are V2 receptors.
ADH binds to V2 receptors and results in insertion of Aquaporin 2 (AQP2) channels on the apical side to allow water into the cell
Water then exits the cell on the basolateral side via Aquaporin channels 3 and 4 (AQP3 and AQP4)
Where does ADH bind?
V2 receptors on he basolateral surface of Collecting Duct Cells
