First Aid 531-535 Renal Flashcards
Best way to estimate GFR?
Creatine clearence
Best way to estimated RPF?
PAH clearence
Normal FF?
20%
How do PGs change GFR, RPF, and FF? What drug would inhibit it?
Prostaglandins preferentially dilate aff arteriole - Inc RPF, Inf GFR, so no change FF. This is inhibited by NSAIDS.
What preferentially constricts efferent arteriole? How does that change GFR, RPF, FF? What drug blocks it?
Angiotensin II, dec RBF, inc GFR, Inc FF. (-) by ACEI
For each of following, how does it affect GFR, RPF and FF? Tell me what inc or dec each one Afferent arteriole constriction Efferent arteriole constriction INC plasma protein concentration DEC plasma protein concentration Constriction of ureter Dehydration
Dec GFR - eff art VC, inc plasma protein conc, ureter constriction, dehydration
Inc GFR - eff art VC, dec plasma protein conc
RPF - only VC of arterioles and dehydration affect it, all dec it.
FF
Afferent arteriole constriction - since both GFR/RPF dec, FF same
Efferent arteriole constriction - GFR inc, RPF dec –> inc FF
Inc plasma protein concentration - dec GFR, no change in RPF –> dec FF
Dec plasma protein concentration - inc GFR, no change in RPF –> inc FF
Constriction of ureter - dec GFR, no change to RPF –> dec FF
Dehydration - dec GFR, dec RPF –> inc FF
How much of something (X) was filtered?
GFR (Creatinine clearence) x Plasma conc of (X)
How much of (X) excreted?
Excretion rate = Vol x Urine conc of (X)
Reabsorption?
Filtered -excreted
Secretion?
Excreted - filtered
Normal plasma level of glucose, where and how much reabsorbed?
Glucose at a normal plasma level (range 60–120
mg/dL) is completely reabsorbed in proximal
convoluted tubule (PCT) by Na+/glucose
cotransport.
At what glucose level will glucose begin to appear in urine?
In adults, at plasma glucose of ∼ 200 mg/dL,
glucosuria begins (threshold). At rate of
∼ 375 mg/min, all transporters are fully
saturated (Tm).
How does pregnancy affect glucose and amino acids resportion in the kidney?
Normal pregnancy may decrease ability of
PCT to reabsorb glucose and amino acids
glucosuria and aminoaciduria.
What is splay?
Splay is the region of substance clearance
between threshold and Tm; due to the
heterogeneity of nephrons.
Reabsorbs all glucose and amino acids and
most HCO3–, Na+, Cl–, PO43–, K+, H2O, and uric acid.
early PCT
Generates and secretes NH3, which acts as a buffer for
secreted H+.
early PCT
Where does PTH work on the nephron? 2 locations, what does it do at each segment?
Early PCT : PTH—inhibits Na+/PO4 cotransport –> PO4 excretion.
Early DCT - PTH— Inc Ca2+/Na+ exchange –> Ca2+
reabsorption.
What does AT II do in PCT?
AT II—stimulates Na+/H+ exchange –> inc Na+,
H2O, and HCO3 reabsorption (permitting
contraction alkalosis).
Major function of thin desc loop of Henle? What is it impermeable to?
Thin descending loop of Henle—passively reabsorbs H2O via medullary hypertonicity
Impermeable to Na+. Concentrating segment. Makes urine hypertonic.
Major function of thick asc loop of Henle? what is it impermeable to?
Thick ascending loop of Henle—reabsorbs Na+, K+, and Cl−.Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through ⊕ lumen potential generated by K+ backleak.
Impermeable to H2O. Makes urine less concentrated as it ascends.
Function of early DCT?
Early DCT—reabsorbs Na+, Cl−. Makes urine fully dilute (hypotonic).
Function of collecting tubule? Regulated by what hormone?
Collecting tubule—reabsorbs Na+ in exchange for
secreting K+ and H+, Regulated by Aldosterone
Aldosterone’s effect in principal cells?
In principal cells: Inc apical K+ conductance, Inc Na+/K+ pump, Inc epithelial Na+ channel (ENaC) activity –> lumen becomes more neg –> inc K+ secretion
Which drug works at early PCT - MOA?
Acetazolamide - inhibits CA, therefore causing NaHCO3 to be excreted, dec HCO3 in body
Aldosterone effect on intercalated cells?
In α-intercalated cells: lumen negativity –> inc H+ ATPase activity –> inc H+ secretion –> inc HCO3
−/Cl− exchanger activity.
ADH works on what receptor at what part of tubule? main effect?
ADH—acts at V2 receptor insertion of
aquaporin H2O channels on apical side.
V2 is at the 2-bules. (of kidney)
What drug works at the thick asc loop? MOA?
Loop diuretics, inhibit N/K/2Cl transporter. This stops that medullary hyperconc, which disallows the concentration of urine.
Which drug works at early DCT? MOA?
Thiazides, (-) Na/Cl transporter, makes urine less dilute (bc w/o the Na, Cl absorption, H2O won’t follow in)
Which drugs work at collecting tubule? MOA?
K sparing diuretics
Spironolactone and eplerenone are competitive
aldosterone receptor antagonists in cortical
collecting tubule.
Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the cortical collecting tubule
Bonus Q - How do loops affect the vascular tone in the kidney? What drug prevents this effect?
Loops stimulate PGE release –> VD effect on aff art. Effect (-) by NSAIDS
Thiazide effect on Ca?
Dec Ca excretion (notice - OPP of loops) - used in osteoporosis, therefore
In Fanconi syndrome - where along the tubule is defect? end result?
Generalized reabsorptive defect in PCT.
Associated with excretion of nearly all amino acids, glucose, HCO3 and PO4.
Bartter - where along the tubule is defect? end result? What drug is that similar to?
Reabsorptive defect in thick ascending loop of Henle. Autosomal recessive.
Affects Na+/K+/2Cl– cotransporter.
Presents similarly to chronic loop diuretic use.
Results in hypokalemia and hypercalciuria
Gitelman - where along the tubule is defect? end result? What drug is that similar to?
Reabsorptive defect of NaCl in DCT. Similar to using lifelong thiazide diuretics. Result - hypoKalemia, hypoMg, hypoCa-uria, and Metabolic alkalosis
Looks like Hyperalosteronism, but with nearly undetectable aldosterone
Liddle syndrome
Liddle - where along the tubule is defect? end result?
Gain of function mutation - Inc Na+ reabsorption in collecting tubules ( inc activity of epithelial Na+ channel)
glycyrrhetinic acid (present in licorice) block what enzyme?
blocks activity of 11β-hydroxysteroid dehydrogenase.
Syndrome of Apparent Mineralocorticoid Excess - def of what enzyme? what metabolic issues?
Hereditary deficiency of 11β-hydroxysteroid dehydrogenase, which normally converts cortisol (can
activate mineralocorticoid receptors) to cortisone (inactive on mineralocorticoid receptors)
Excess cortisol in these cells from enzyme deficiency –> inc mineralocorticoid receptor activity –> hypertension, hypokalemia, metabolic alkalosis.
Let’s look at pg 539 (2016) together, bc there is no way I can make a flash card on it.
The q I got showed the graph exactly and asked me to pick what line corresponded to (x) listed in q stem.
3 stimulations to secrete renin?
Dec BP (JG cells) Dec Na+ delivery (macula densa cells) Inc sympathetic tone (B1-receptors)
Why do you not get reflex brady with AT II?
Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor
effects. Helps maintain blood volume and blood pressure.
ANP, BNP - what second mediator? effects on arterioles?
cGMP, VD aff art, VC eff art
Aldosterone is released in response to what change in blood? (Don’t say AGII)
dec blood volume and Inc plasma K+
3 cells of JGA? Which of these cells actually secrete renin?
Consists of mesangial cells, JG cells (modified
smooth muscle of afferent arteriole) and the
macula densa (NaCl sensor, part of DCT). JG cells secrete renin
enhances K+ and H+ excretion by way of principal
cell K+ channels and intercalated cell H+ ATPases
Aldosterone
aquaporin insertion in principal cells? end result?
ADH - leads to inc H20 absorption
3 effects of AG II (other than hormones)
VC, (via ATII1-R) of vasc smooth musc
VC of eff art –> preserve FF
inc PCT Na+/H+ activity –> Na, HCO3, H20 reabsorption
(+) HT –> thirst
Released by interstitial cells in peritubular
capillary bed in response to hypoxia.
EPO
Paracrine secretion vasodilates the afferent
arterioles to inc RBF.
PGs
Secreted by PCT cells, promotes natriuresis.
Difference between low and high dose?
Dopamine
At low doses, dilates interlobular arteries, afferent arterioles, efferent arterioles –> Inc RBF, little or no change in GFR.
At higher doses, acts as vasoconstrictor.
Bonus Renal Q…ready??
Yes you are!
62 yr old man comes to primary physician with complaints of urination at night, lethargy, and general malaise. BUN = 4.0, Creatine 3.5, ttl Ca = 7.4 mg/dL, se PO4 = 5.5 mg/dL. Has normochromic, normocytic anemia. Started on Ca supplements, and PO4 restricted diet. Primary Tx for pt’s anemia?
EPO - EPO is likely low in this pt with chronic renal failure, bc it’s made with peritubular capillaries lining the renal cortex.
A young man brings in his 3yr old daughter to ER, She began vomiting 2 hrs ago. As he looked thru the medicine cabinet for something to give her, he noticed a few bottles were missing. The daugher admitted to taking them, and eating “candy” from one of them 2 days ago. The bottle turns out to be expired tetracyclin. . Lab show se PO4 of 1.8, and urine shows high amts of glucose. 24 hr urine show hyperphosphaturia. What is this pt at risk of developing?
AML Acute tubular necrosis Diarrhea and dermatitis kidney stones systemic acidosis
Choice E is correct.
Glucosuria + HyperPO4 = Fanconi syndrome
Can be caused by inherited disorders like Wilson’s or acquired (like the expired tetracycline)
Pt will have dysfunction proximal renal tubules and do not reabsorb glucose, phosphorous, amino acids, or bicarbonate. It is one cause of renal tubular acidosis –> pts develop systemic acidosis with normal anion gap.
Another possible complication of Fanconi syndrome = hyperphosphatemic rickets
Fanconi syndrome due to tetracycline degradation will resolve in few months.
AML = Fanconi anemia
ATN = death of tubular cells (not just temporary dysfunction) - muddy brown casts in urine, due to nephrotoxic Rx and pre-renal azotemia
Diarrhea+dermatitis - Hartnup disease, pellagra like sx, dec Trp absorption in renal tubules
Kidney stones - AR cysteinura, , cant absorb cysteine in renal tubules –> cysteine stones
Two drugs that target ENac?
Triamterene, Amiloride
Spironolactone used in what non renal disease?
PCOS (due to anti androgen effect)
