Functions of the Kidney Flashcards
Where are the main sites of sodium recovery
PCT (majority) and Loop of Henle , some in Distal tubule
What are the three layers of ultrafiltration and which is the urinary side and luminal side
Endothelial cell ⇒Luminal side= blood
Glomerular basement membrane in middle
Slit diaphragm ⇒ Urinary side = Bowman’s Space
What makes up slit diaphragm and what is its function
Podocytes - glomerular epithelial cells.
Pinocytosis of trapped proteins
What is the role of mesangial cells
- GBM in middle renewed by mesangial cells- which remove old membrane and lay down new membrane
What is the role of endothelial cells in filtration
- Cleaned by blood flow and phagocytes (eg. neutrophils, macrophages
- Fenestrae allow large proteins to go through but keeps cells out
How is creatinine used to measure filtration rate, what are the assumptions
- GFR= Clearance = urine conc. x urine flow rate/ plasma conc.
- Assuming that clearance = GFR since no way to bring creatinine back into body
Where does Na get moved to by Na+/K+ ATPAse
Basal side (3 Na in exchange for 2 K+)
Organic anion transporters(OATs) ⇒ Which drugs , passive or active movement? What ion is involved and in what direction
Methotrexate, furosemide and penicillin
OA actively pushed in actively tgt with Na+ as Na+ sent out through Na/K pump but OA passively drifts out
Drug that affects OATs
Probenecid can be used to block OAT and slow export of drugs to ameliorate toxicity of penicillin
Organic anion transporting polypeptides(OATPs)⇒ diff from OATs?
- Larger, somewhat Hydrophobic. Egs are Prostaglandins, cholate, cipro, cyclic peptides
Are OCTs active or passive
Example of pumps related to this
Any ion involved and if so what dir
- Cations drift into the cell passively to equilibrate due to conc. gradient, cytoplasmic conc. should not exceed that of plasma
- These cations are pumped out actively
Eg. MDR1 which uses ATP
MATE antiporter which kicks OC out in exchange for H coming in
- These cations are pumped out actively
What are pulled into the PCT by na gradient
Glucose, amino acids, cl-, phosphate
Is water recovered in PCT
yes, due to osmotic gradient
How much NaCL, Phosphate, calcium etc. is resorbed in PCT
65
How is sodium resorbed in PCT
by exchange with H+ going out
How much HCO3- resorbed at PCT and how
85-90%, cycling with H+
- H+ combines with HCO3- in lumen to form H2CO3, converted to H2O by CA, and CO2 which enters the cell
- H2O combines with CO2 again to form HCO3- and H+
- HCO3- Goes out with Na+ or against CL- which comes in
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-
i
All HCo3- is used up, Still has H+ when HCO3- all taken up ⇒ H+ combines with HPO42- instead of HCO3- to from H2PO42-
OR
glutamine broken down in cell to form NH3 which goes into lumen through diffusion and combines with H+ (uses Na+/H+ exchanger) to form NH4+
NH4+ may also be formed intracellularly and excahnged against Na
What happens to H+ or HCO3- if body is still in acidosis
All HCo3- is used up, Still has H+ when HCO3- all taken up ⇒ H+ combines with HPO42- instead of HCO3- to from H2PO42-
OR
glutamine broken down in cell to form H+ and HCO3- and NH3 which goes into lumen through diffusion and combines with H+ (uses Na+/H+ exchanger) to form NH4+
NH4+ may also be formed intracellularly and exchanged against Na
q
All HCo3- is used up, Still has H+ when HCO3- all taken up ⇒ H+ combines with HPO42- instead of HCO3- to from H2PO42-
OR
glutamine broken down in cell to form NH3 which goes into lumen through diffusion and combines with H+ (uses Na+/H+ exchanger) to form NH4+
NH4+ may also be formed intracellularly and exchanged against Na
Difference between Intercalated Cells A and B
A corrects for acidosis by excreting H+ for K+ ( and HCO3- gets resorbed for exachange with Cl-) while B corrects for alkalosis by excreting HCO3- for Cl- and H+ gets resorbed into the bpdy by H+ ATPase (H+/K+)
What do amino acids enter the PCT with
Na+ and Cl-
How are proteins reuptaken?
Using general receptors like megalin => receptor mediated endocytosis
Uptake of Ca2+, Mg2+ ?? IN PCT??
Passive mainly, driven by osmosis
Uptake of PO42- in PCT?
with Na, like glucose
How much urea is reabsorbed in PCT
50% , follows water
- What is resorbed passively in LOH and where
Ca and PO42- @ TAL
How and where is sodium resorbed at LOH and how much
What happens to K +
Further 25%, tgt with 2Cl-, and K+ @TAL
Regulated leakage of K+ at ROMK
How is the movement of water at TAL
NO movement, movement is at TDL instead
How much salt and water has been recovered at distal tubule
-
95% salt, 75% water
How is salt resorbed at distal tubule and how does it vary at different parts
- In first part of distal tubule
- Symporter protein (Na+/Cl-)
- In distal part
- Na+ ions are exchanged for H+ or K+ ions ( stimulated by aldosterone and regulated pH of the urine and body)
SAME AS CD
- Na+ ions are exchanged for H+ or K+ ions ( stimulated by aldosterone and regulated pH of the urine and body)
Calcium reuptake in the kidneys can be regulated by what hormone ?? Where?? What happens? How is Vit D involved?
PTH @ PCT
Inhibits uptake of Po42- which is usually tgt with Na+ at apical side of cell.
Promotes uptake of Ca2+ via TRPV5 (channel), Ca2+ binds to calbindin in cells and exported out of cell through transporter . PTH increases all three. Vit D required for calbindidn and basal transporter
- How much sodium is resorbed at CD??
2-5%
How much water is removed at CD and how is it driven
Up to 24 %, driven by hypertonic zone formed by LOH
- How does osmolarity and volume at bottom of CD compare to bottom of LOH
Same osmolarity, but volume very different, much lower
K+ ⇒ two main cell types involving it at CD and do they excrete or reabsorb K+
Intercalated cells →Re-absorption
H+ exported out in exchange for K+, also leaves through ATPase alone
Principal cells → regulated excretion by apical K+ channel
How many % of K is absorbed form PCT to DCT
90% ( similar to sodium)
How does aldosterone affect K+ levels in CD
It increases ASC and Na+/K+ pump to increase amount of Na+ taken in and amount of K+ excreted.
(NB: K+ channel NOT affected)
In intercalated cells, it increased H+ pump so reduced K+ coming in exchange for H+ leaving
Low k+ and High K+ diet affect on Prinicipal cells
Low K+ → tyrP (phosphorylation) of apical K+ channels so channels removed from membrane
High K+ diets cause loss of tyrP (phosphorylation) and channels accumulate in membrane
How does acidosis (acute and chronic) and alkalosis affect K+
- Alkalosis ⇒ Hypokalemia H+ out pumping by intercalated cells reduced so less K+ reabsorbed. Apical K+channel activity (and NA+/K+ activity) increased in principal cells so more K+ lost
- Acidosis (acute) ⇒ Hyperkalemia opp of above
- Acidosis (chronic) ⇒ Less efficient Na pump in PCT so urine more copious and flushes K+ away
a
- Alkalosis ⇒ Hypokalemia
H+ out pumping by intercalated cells reduced so less K+ reabsorbed.
Apical K+channel activity increased in principal cells so more K+ lost - Acidosis (acute) ⇒ Hyperkalemia opp of above
- Acidosis (chronic) ⇒ Less efficient Na pump in PCT so urine more copious and flushes K+ away
What is bartter’s syndrome
Impaired SLC12A2 @ TAL of Loop of Henele → Import of 2Cl-, K+, Na+’
- Loss of Na+, K+, much H2O, hypercalcuria
- Similar effect to high dose of loop diuretic
- Increased concentration of Na+ in urine
- Usually K+ ions leak out through apical membrane through ROMK, causing electircal gradient ( Urine more electropositive)
- Hence Ca2+ will move from urine into cell
- *This mechanism is disrupted by Bartter’s syndrome→Hypercalcuria/ hypocalcaemia
Gietlman’s syndrome
Impaired SLC12A3@ distal tubule →Na+/Cl- reuptake system
Loss of Na+, K+, H2O, hypocalcuria
Reduced uptake of Na+ in distal tubule→ increased uptake of Ca2+ in distal tubule
Liddle’s Syndrome
Hyperactive ASC (=ENaC) @ Collecting Duct
ASC normally modulated by aldosterone⇒ problems with it results in??
Volume expansion(body), hypertension⇒ treat with??
Can be treated with amiloride to block the channel
Pseudohypoaldosteronism
- Churning out aldosterone to increase Na+, but no effect on ASC⇒ problems result in??
- Na+ loss and K+ retention, high aldosterone
Inactivating mutations of aquaporins (AQP 2 ) ⇒ What does this lead to? effect if AQP 1 inactivated?
- No effect if it inactivates AQP 1
- Leads to Diabetes Insipidus (polyuria/polydipsia)
What is the myogenic mechanism
Stretch activated cation channels depolarize the membrane and cause smooth muscle to contract, fast and protective against acute surges
How does tubuloglomerular feedback work?
- If BP is too high, there will be high filtration in glomerulus and high BP in distal tubule
- Signals sent to afferent arteriole from JG to constrict and reduce filtration due to high Na+ at macula densa
- Specialized JG cells are sensitive to the concentration of NaCl in tubular fluid, pressure in the afferent artery and signals from the SNS (B1)
- Signals sent to afferent arteriole from JG to constrict and reduce filtration due to high Na+ at macula densa
What happens to renin levels in Renal artery stenosis
Increased Renin from JG cells due to reduced sodium
When will adenosine be produced by the kidney and what does it do
High Na in macula densa results in JG cells releasing adenosine and afferent arteriole will constrict in response to adenosine, reducing glom blood pressure
What is the final hormone produced by RAAS
Angiotensin II
What hormones are released as a result of Ang II?
- Vasopressin and Aldosterone
- Vasopressin stimulates thirst and increases water resorption, aldosterone increases Na+ resorption
What is the effect of angiotensisn II on vessels
Vasoconstriction of arterioles, as well as efferent arteriole constriction in kidneys
What is the effect of renin on the vessels (systemic)
It causes constriction of the arteriolar vessels indirectly through Ang II
What is the effect of angiotensin II on kidneys (uptake of ions)
Acts on the PCT to increase uptake of Na in exchange for H+ by activating the exchanger
What is another effect as a result of decrease in renal perfusion apart from JGA activation, and what hormone/ system causes it
Ang II and signals from macula densa causes sympathetic activation through renal nerves can cause activation of SNS, renal nerves secrete noradrenaline which constricts both afferent and efferent cessels, reducing flow. SNS also directly promotes renin release.
What is the effect of ANP on kidney cells
It blocks ASC at collecting duct and causes more sodium loss
What is the effect of aldosterone on CD cells
Intercalated cells - it drives the export of Proton channel to cell surface so that less H+ is exported in exchange for K+ into the cell
In the principal cell, it drives the increase in production of ASC and Na+/K+ pump so more Na is recovered
Difference between PCT and DCT cells
PCT cells have microbilli.
What toxic substances are excreted actively by the kidney
creatinine, uric acid and many drugs
is the DTL and ATL permeable to urea?
DTL NO, ATL YES - similar to ions
Is the TAL more or less osmplar than glomerulus
Less, because 25% salts lost at LOH but only 10% water
Does efferent arteriole flow next to descending or ascending limb
Ascending
is water resorbed at DCT
NO! only CD
