Lecture 5: continuing regulation of pH, regulation of blood Ca2+ levels, renal failure

explain mechanism of adding new HCO3- in proximal tubule

1. glutamine enters proximal tubule via apical membrane via facilitated diffusion or secondary Na+ active transporter on basolateral membrane

2. glutamine breaks down into NH4+ and HCO3-

3. (1) HCO3- absorbed (2) NH4+ secreted via Na/H exchanger and excreted

4. Result is net gain of HCO3- and net loss of H+

explain mechanism of adding new HCO3- in distal tubule and collecting dut

1. H2O + CO2

2. carbonic anhydrase

3. H2CO3 splits into HCO3- and H+

4. HCO3- passively absorbed into ISF (net gain of HCO3-); H+ actively transported into tubular lumen

5. H+ + HPO4 (filtered) → H2PO4 excreted

• Once all the bicarbonate has been reabsorbed, secreted H+ is buffered by filtered phosphates, which can’t be reabsorbed

P cell (what gets secreted and absorbed?)

Na+ and H2O reabsorbed, K+ secreted

alpha intercalated cell (what gets secreted and absorbed?)

HCO3- absorbed, H+ secreted

• active most of the time b/c we’re usually under an acid loud

beta intercalated cell (what gets secreted and absorbed?)

H+ absorbed, HCO3- secreted

• only active if we are alkalotic

kidneys adjust pH by

altering absorption or secretion of HCO3- (plasma [HCO3-])

effect of adding lactic acid to the blood on pH, H+, HCO3-, Pco2

• pH decreases

• H+ increases

• HCo3- decreases

• Pco2 no change

effect of adding Hco3 to the blood on pH, H+, HCO3-, Pco2

• pH increases

• H+ decreases

• Hco3 increases

• Pco2 no change

effect of hypoventilation on pH, H+, HCO3-, Pco2

• pH decreases

• H+ increases

• Hco3 no change

• Pco2 increases

effect of hyperventilation on pH, H+, HCO3-, Pco2

• pH increases

• H+ decreases

• Hco3 no change

• Pco2 decreases

respiratory acidosis

• primary defect

• how do kidneys respond

• compensatory response

• primary defect: increased Pco2

• alpha intercalated cells secrete H+ and reabsorb HCO3-

• compensation occurs via renal responses and will result in increased HCO3- in blood level and pH that is increased toward normal

metabolic alkalosis

• primary defect

• what receptors sense the change and what is the respiratory response

• how does respiratory response affect pH?

• primary defect: decreased H+ (or increased Hco3-)

• sensed by peripheral chemoreceptors and causes decreased ventilation

• respiratory response → decreased pH

PTH

released by the parathyroid glands in response to decreased plasma Ca2+

PTH stimulates (3 things)

• increased bone breakdown

• formation of calcitrol (active form of vitamin D3) by the kidney

• increased Ca2+ reabsorption by the kidney

calcitrol

active form of vitamin D3; stimulates Ca2+ (and phosphate) absorption by the intestine

PTH inhibits

phosphate reabsorption by the kidney → increased urinary excretion of phosphate

fill this out

if PTH induces bone resorption thus increased plasma Ca2+ and PO4, then why does PTH decrease PO4 reabsoprtion?

• because PTH also stimulates PO4 absorption by the intestine

• and high plasma PO4 promotes Ca2+ deposition in bone

• so decreasing PO4 absorption by kidney blunts the increase in plasma PO4 and helps keep the released Ca2+ in the plasma compartment rather than driving it to be deposited back into bone

erythropoietin

released by the kidney in response to decrease O2 delivery to kidney and stimulates production of RBC and increases blood Hb concentration

chronic renal failure

a progressive disease process consisting of loss of filtration (decreased GFR)

effect of chronic renal failure on plasma K+

hyperkalemia: K+ secretion/excretion is impaired

effect of chronic renal failure on arterial pH

acidosis: HCo3- reabsorption/addition is impaired

effect of chronic renal failure on hematocrit

anemia: low RBC, due to decreased erythropoietin secretion

effect of chronic renal failure on waste excretion? plasma [waste products]?

wastes are not removed so waste products increase in blood (plasma urea and creatinine levels go up, for example)

effect of chronic renal failure on bone density

decreases due to increased bone breakdown

• decreased ability to reabsorb filtered Ca2+ AND decreased calcitriol activation (so decreased Ca2+ absorbed from GI tract) → decreased plasma Ca2+ → increased PTH → increased bone breakdown

effect of chronic renal failure on urinary excretion of protein

protein appears in urine

• glomerular filtration barrier breaks down and proteins are filtered and excreted

effect of chronic renal failure on blood pressure

• Na intake must be monitored. If increased intake, increase volume and BP (and vice versa)

• increased renin secretion from damaged nephrons due to low GFR → increase Ang II and TPR → increase BP

effect of chronic renal failure on plasma osmolarity

• ability to dilute and concentrate urine is diminished. therefore, ability to excrete or retain water is diminished.

• if increase water intake, can decrease osmolarity (and vice versa)

calcitonin

• stimulated by increased plasma Ca2+

• reduces bone breakdown or stimulates bone formatiob

• decreases renal absorption of Ca2+ and phosphate.