4/5- solute + water handling

what’s the most important contributor to the body’s extracellular fluid (ECF)

Na⁺

4 parts of the nephron that reabsorbs filtered Na+

1. proximal tubule: ~67%

2. thick ascending loop of Henle (TAL): ~25%

3. DCT + cortical collecting tubule: ~5%

4. medullary collecting duct: ~3%

Na⁺ reabsorption involves which 2 things

1. apical ENaC (epithelial Na⁺ channel)

2. basolateral Na-K pump

in the 1st ½ of proximal tubule, Na⁺ is reabsorbed w/

HCO3⁻ + other solutes (e.g., glucose, amino acids, Pi, lactate)

in the 2nd ½ of proximal tubule, Na⁺ is reabsorbed w/

Cl^-

2 mechanisms the proximal tubule reabsorbs Na⁺ + Cl^-

1. transcellular: crosses apical + basolateral membranes before entering blood

2. paracellular: move through tight junctions between cells

T/F: proximal tubule is permeable to water

true

what happens when the 1st ½ of the proximal tubule doesn’t work

Fanconi syndrome: renal disease from inability to reabsorb HCO3⁻, Pi, amino acids, glucose, low-molecular-weight proteins

2 drugs that target the proximal tubule

1. mannitol

2. carbonic anhydrase inhibitors (acetazolamide)

mannitol mechanism of action

osmotic diuretic that’s filtered into proximal tubular space where it increases tubular fluid osmolality → impaired reabsorption of fluid + increased excretion of water

carbonic anhydrase inhibitors (acetazolamide) mechanism of action

• inhibits carbonic anhydrase, which normally facilitates HCO3^- reabsorption

• leads to metabolic acidosis

• used to treat glaucoma

how is Na⁺ reabsorbed in the thick ascending loop of Henle (TAL)

1. Na/K/Cl cotransporter (NKCC2):

2. NHE3

T/F: TAL is permeable to water

false, it’s impermeable so it’s called the “diluting segment”

where can you find the most diluted urine in the nephron

end of TAL/tip of thin descending loop

how is Na⁺ reabsorbed in the DCT

Na/Cl cotransporter

T/F: DCT is permeable to water

false, it’s impermeable

how is Na⁺ reabsorbed in the cortical collecting tubules (CCT)

via principal cell: Na⁺ crosses the apical membrane of principal cell through epithelial Na channels (ENaC)

what can modulate # of open ENaCs

changing levels of aldosterone or AVP/ADH

A. proximal tubule

kidneys have a high O₂ consumption because

Na⁺ reabsorption is dependent on ATP-driven Na-K pump

C because proximal tubule absorbs ~67% so multiply 0.67 w/ 18 mEg/min = 12 → 18-12 = 6 mEq/min

B because osmolality of Na does not change

when would the osmolality of Na change

osmotic diuresis: poorly permeable substances are present in the plasma + glomerular filtrate (ex: infusion of sucrose + mannitol, untreated diabetes mellitus)

what are the numbers

1. Cl^-

2. Na⁺ osmolality

3. P_i

4. HCO₃^-

5. glucose

6. lactate

7. amino acids

in the absence of AVP, _____ have relatively low water permeability

TAL + all downstream segments

3 things that increase Na⁺ reabsorption

1. renin-angiotension aldosterone

2. AVP/ADH

3. sympathetic activity

4 things that decrease Na⁺ reabsorption

1. ANP

2. prostaglandin

3. bradykinin

4. dopamine

what’s the glomerulotubular (GT) balance

causes fractional Na⁺ reabsorption by modulating rate of NaCl reabsorption in proximal tubule

what’s Bartter syndrome

autosomal recessive disease that inactivates the gene coding for Na/K/Cl symporter → decreased NaCl + K reabsorption → decreased ECFV, hypokalemia, metabolic alkalosis, hyperaldosteronism

which organ produces urea

liver, produces it from ammonia

kidneys regulate blood urea nitrogen (BUN) to what levels

7-18 mg/dL

what causes urea retention

renal disease → decreased GFR → urea retention + increased BUN

what happens to glucose in the nephron

proximal tubule reabsorbs almost all of filtered glucose via Na/glucose cotransporter (SGLT)

glucose should not be in urine (zero clearance) as long as blood glucose level is below

~180 mg/dL

rate of glucose reabsorption plateaus at what value

~400 mg/min → SGLT1 + SGLT2 cotransporters become saturated

what’s Hartnup disease

autosomal recessive disease → neutral + ring structured amino acids not absorbed + excreted through urine

what’s the safety mechanism when a protein is not reabsorbed

reabsorbed via clathrin coated endosomes

what’s urate + how much of it is reabsorbed

it’s the end product of purine catabolism + proximal tubule reabsorbs 90% of it

uricosurgic agents are used to

inhibit urate transporters to treat gout (elevated urate level)

luminal pH affects the clearance of what

weak acids: decreased luminal pH → reabsorption of neutral weak acids + secretion of neutral weak bases

how do we combat decreased luminal pH aka salicylate (aspirin) toxicity

1. alkalinizing urine w/ HCO₃^-

2. increasing urine flow w/ diuretics

T/F: some phosphate excretion occurs even at normal levels

true, therefore a small increase in phosphate level → significant acceleration of phosphate excretion

what’s the key promotor of phosphate excretion

parathyroid hormone (PTH), inhibits sodium/phosphate uptake

what’s the most important regulator of renal Ca²⁺ reabsorption

PTH + vitamin D stimulate calcium reabsorption

where in the nephron does PTH stimulate Ca²⁺ reabsorption

TAL + DCT

what drug is used to treat hypocalcemia (low calcium blood level)

loop diuretic, furosemide

Mg²⁺ behaves like which ion

Ca²⁺