Physio

Question 1

RAA System

Which metabolites cause side effects

Answer 1

Cough = Bradykinin (accumulation of toxic) - protussive

Angioedema - bradykinin

Hypotension - AT2

Question 2

Where and what Sodium/Glucose coTransporters in body?

Answer 2

SymPorters

Kidney- SGLT 2 - 90% of renal glucose absorption - all occurs in proximal tubule.
Gene is SLC5A2 (On Chromosome 16)
This pump (on apical surface) is driven by gradient generated by NaKATPase pump on basolateral (3Na out of 2K in)
Sugar into blood stream by GLUT2 on basolateral

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Vs. GUT
Sodium Glucose coTransporter SGLT1 (X Chromosome) - trivial expression in kidney
Absorbs glucose and galactose - in exchange for 2 Na - ATP INDEPENDENT
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UniPorters
“Facilitated diffusion” down concentration gradient (Channel because glucose too big to just diffuse across membrane)
GLUT 5- absorbs fructose from lumen (5% of pop deficient)
GLUT 2 - Sugar out of cells into blood stream

Question 3

NSAIDs MOA on Renal Failure?

Answer 3

COX-inhibition
Decreased production of PGE
PGE are regulatory vasodilation
Therefore unapposed vasoconstricition and nil GFR (As in medical nephrectomy)
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Also Acute Interstitial Nephritis (looks like ATN but also rash and eosinophils)

Question 4

Absoprtion of Na across Nephron?

Answer 4

65% PCT
15 % LoH
15% DCT
5% CD

Question 5

RAA System?

Answer 5

Renin (Kidney)
AngiotensionOGEN (Liver)

Low BP at AA or Low Na at DCT - Renin
Renin + AT-OGEN => AT1
AT1 + ACE (Lungs) => AT2
AT2 - Vasoconstricts EA, Generalised Vasoconstrictior, Stimulates adrenal to make ALDOSTERONE to modify DCT, Stimulated Hypothal to make ADH @ Post. Pit to modify CD AquaPorins,

Question 6

Aldosterone MOA

Answer 6

“Mineralocorticoid”
Secreted from ADRENAL CORTEX in response to High K, or AT2, ACTH
DCT and CD

Acts on Mineralocorticoid Receptor
Upregulates Basolateral Na/K Pump
Upregulates Epithelial Na (sodium) Channels (ENaCs)
Sodium INTO Cell, Potassium OUT of cell

Question 7

Frusemide - MOA

Answer 7

Loop Diuretic
Therefore powerful
Inhibits Na-K-Cl Cotransporter (NKCC2), (Gene is SLC12A2 = SoLute Carrier Family 12 member 2) in Thick ascending LOH
Inhibition causes Loss of Na, K, Cl into urine

Physi
SYMPORTER, Na,K,2Cl Cotransporter
Uses Na gradient generated by basolateral NaK-ATPase - “Secondary active transport”

Defect of chromosome 5 = Bartter Syndrome (Low K, Alkalosis, Activation of RAAS,m HYPER Calcuria)

Question 8

Thiazide MOA

Answer 8

Acts upon Thiazide sensitive Na-Cl symporter in DCT

In health - Na-Cl absorbs from lumen

Under effect of Thiazide Na and Cl absorption is lowered
Basolateral Na/Ca Antiporter causes calcium to leave cell
TRPV5 (Apical Ca selective channel) then faciliates absoprtion of calcium from lumen - allows Rx of hypercalciuria

Genetically “Gitelman - SLC12A3, Solute Carrier 12, Member 3, On chromosome 16”
Low K, Metabolic Alkalosis, Low Na, Low Mg, High Ca

Question 9

Fractional Excretion of Sodium?

Answer 9

URINARY SODIUM x plasma creat
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Plasma sodium x urinary creat