Physiology Review II Flashcards
proximal tubule
fluid that enters - isotonic
-concentration of substance equals plasma concentration for freely filtered substances
sodium in proximal tubule
2/3 filtered is reabsorbed
- driven by basolateral Na/K ATPase
- glomerulotubular feedback
catecholamine and ANG II
stimulate basolateral ATPase to increased Na reabsorption
-proximal tubule
water and electrolytes in proximal tubule
2/3 filtered H2O, K, and Cl (leaky) follow the sodium gradient
end of proximal tubule
osmolality of Na and K have not changed significantly
-but one third of filtered remains
SGLT-2
sodium-glucose linked transporter type 2
- in the kidney
- glucose and Na cotransport
metabolites in the proximal tubule
proteins, peptides, AAs, ketone bodies reabsorbed via secondary active transport
-linked to sodium transport
bicarbonate in the proximal tubule
80% reabsorbed
- combines with H+ in lumen to CO2 and H2O
- luminal carbonic anhydrase
- H+ pumped into lumen, exchanged for sodium
- also H + ATPase
- CO2 - crosses luminal membrane - combines with water
- reforms H and bicabonate
- H pumped back into lumen and bicarb exits basolateral membrane
important factor for proximal tubule H+ secretion
concentration of H+ in cell
- acidosis - increased H secretion and bicarb reabsorption
- alkalosis - decreased H secretion and bicarb reabsorption
ANG II
stimulates Na/H antiporter
-volume depleted state - increased bicarb reabsorption
uric acid in the proximal tubule
breakdown of nucleotides - xanthine oxidase
-90% is reabsorbed in proximal tubule
low pH - urate > uric acid - precipitate out - stone (gout)
secretion in proximal tubule
organic anions/cations
-PAH, inulin, PCN, atropine, morphine
concentration of inulin along tubule
index of water reabsorption
inulin concentration
freely filtered - concentration in BS = plasma
- water reabsorbed, inulin is not - [inulin] increases along tubule
- 2/3 reabsorbed in PT - inulin concentration triples
[highest] in collecting duct
loop of henle
fluid entering is isotonic - but volume is 1/3 filtered
- countercurrent mutliplier
- creates concentrated medulla
- predominantly NaCl and urea
- caused by juxtamedullary nephrons (surrounded by vasa recta)
descending limb loop of henle
permeable to water (15% reabsorption here)
-impermeable to solute
ascending limb loop of henle
impermeable to water
-solutes transport out
Na/K/2Cl transporter
thick ascending limb of loop of henle
- electroneutral
- reabsorb 25% filtered Na, Cl, and K
there is a K channel - allows diffusion back into lumen
calcium sensing receptor
basolateral membrane - ascending thick limb
- GPCR
- net effect - inhibit Na/K/2Cl transporter
- reduces positive luminal potential (less K back out)
- in turn decreases calcium reabsorption
**high plasma calcium can reduce ascending thick limb calcium reabsorption
distal tubule
early distal tubule - reabsorbs Na, Cl, Ca
NaCl in dustal tubule
crosses apical membrane via NaCl symporter
- Na across basolateral - Na/K exchanger
- Cl across basolateral through channels
impermeable to water - decreases osmolality further
calcium in distal tubule
passive entry though channels
-regulated by PTH
-basolateral transport - Ca ATPase or 3Na-Ca antiporter
calbindin
distal tubule cells
- facilitates calcium reabsorption
- increased with vitamin D
collecting duct
principal cells and intercalated cells
principal cells
luminal epithelial Na channels (ENaC)
-sodium follows its gradient established by basolateral Na/K ATPase
creates negative luminal potential - Cl left in lumen
-results in potassium secretion
reabsorption of sodium and secretion of K linked**
aldosterone
increases ENaC and basolateral Na/K ATPase of principal cells
increased sodium reabsorption and increased K secretion
ADH
aka AVP
- acts on V2 receptors
- increases aquaporins on principal cells
increased water reabsorption**
intercalated cells
acid-base regulation
- luminal H+ ATPase - pumps H+ into lumen
- secreted H+ buffered via ammonia and phosphate
aldosterone
stimulates H+ ATPase of intercalated cells
-excess - can lead to metabolic acidosis
proximal renal tubular acidosis type II
diminished capacity of proximal tubule to reabsorb bicarb
- low plasma bicarb and acid urine
- ex/ fanconi syndrome
- serum potassium low
bicarb lost in urine - lost as sodium bicarb - pulls water with it - creates osmotic diuresis - diuresis leads to loss of potassium in urine
distal renal tubular acidosis type I
inability of distal nephron to secrete and excrete fixed acid
metabolic acidosis with high urine pH
-serum potassium low
renal tubular acidosis type IV - hypoaldosterone states
cannot secrete potassium (hyperkalemia)
-decreased H+ secretion - metabolic acidosis
due to diabetic nephropathy (low renin)
drug that (-) RAAS
trimethoprim
addisons disease - decreased aldosterone from adrenal cortex
potassium balance
98% inside cells / 2% outside cells
>5 hyperkalemia / < 3.5 hypokalemia
gradient caused by the negative intracellular potential
insulin and epinephrine
stimulate Na/K ATPase - can reduce plasma K
activity of Na/K pump
3 Na out
2 K in
acidosis
potassium from ICF to ECF
-hyperkalemia
also with cell shrinkage
alkalosis
potassium from ECF to ICF
-hypokalemia
also with cell swelling
potassium secretion
determined by filtrate flow and sodium reabsorption (negative luminal potential)
increased potassium secretion
increased flow
increased aldosterone
decreased potassium secretion
decreased flow
decreased aldosterone
hyperkalemia
stimulates aldosterone
H+ and K+ balance
to keep electroneutrality
- administer bicarb - protons out of cell/ K into cell
- results in hypokalemia
insulin
increased Na/K ATPase
-more K into cells
hyperkalemia clinical
muscle weakness and fatigue
high T wave - eventually to V-Fib
metabolic acidosis
hypokalemia clinical
muscle weakness, general fatigue
hyperpolarization - delays repolarization
low T wave, high U wave
decreased insulin response to carbohydrate load, decreased growth in children, nephrogenic DI, metabolic alkalosis
diuretics
increased flow - hypokalemia
acute renal failure
rapid loss of renal function - often reversible
increased BUN/Cr
prerenal failure
decreased renal perfusion
- decreased GFR
- reduced FeNa - increased reabsorption
- elevated BUN/Cr - however, increased water reabsorption > increased urea reabsorption > higher elevation of BUN compared to Cr
FeNa
fractional excretion of sodium
intrarenal failure
tubular damage occurs
- increased FeNa
- casts in urine
- low BUN/Cr
postrenal failure
obstruction of outflow from kidney
- early - decreased FeNa, increased BUN/Cr
- late - pressure increases - to intrarenal failure - increased FeNa and decreased BUN/Cr
chronic renal failure
irreversible loss of nephrons
- causes glomerular HTN to remaining glomeruli
- leads to fibrosis/scarring
- elevated BUN/Cr
- volume overload and edema
- hyperkalemia
- metabolic acidosis
- hyperphosphatemia - reduces plasma Ca - increased PTH (secondary hyperparathyroidism)
- cannot hydroxylate Vit D enzmye - hypocalcemia
- anemia - decreased erythropoietin
most common cause*** - diabetic nephropathy
second most common cause - HTN
