ICL 1.7: Acid Base Physiology Flashcards
what are normal pH, HCO3 and PaCO2 levels?
pH = 7.4 (7.35-7.45)
[HCO3] = 24 mEq (22-26)
PaCO2 = 40 mmHg (35-45)
what is the henderson hasselbach equation?
pH = pKa + log[HCO3]/[CO2]
how do the kidneys compensate for respiratory acidosis?
Kidneys retain HCO3- by increasing reabsorption and/or generating new HCO3
[HCO3-] increases
how do the kidneys compensate for respiratory alkalosis?
the kidneys eliminate HCO3- from the body by reducing reabsorption and/or increasing secretion
[HCO3-] decreases
how is the acid-base equilibrium balanced out?
- reabsorb HCO3- in the proximal tubule
- secrete limited amounts of organic bases or weak organic acids and acid equivalents in the proximal tubule
- secrete protons or bicarbonate in the distal nephron (mostly collecting tubules)
- urine pH varies from 4.5 to 8.0
what is the overall scheme for excretion of a base?
to excrete base
1. freely filter HCO3
- reabsorb the majority of filtered HCO3
- reabsorb some additional HCO3
- secrete some HCO3
- excrete alkaline urine containing HCO3
what is the overall scheme for excretion of an acid?
- freely filter HCO3
- reabsorb the majority of filtered HCO3
- reabsorb some additional HCO3
- secrete H+ and NH4+
- excrete acidic urine containing NH4+
where is HCO3 reabsorbed along the nephron?
most of the filtered HCO3− is reabsorbed in the proximal tubule (80%) then the rest is reabsorbed in the thick ascending limb (15%)
in the distal nephron you can reabsorb more or secrete depending on what you need to do
virtually no HCO3− remains in the final urine
what happens to HCO3 in the proximal tubule?
- H+ ions, secreted into the tubular lumen combines with filtered HCO3- to form CO2 and H2O via carbonic anhydrase
CO2 combines with H2O in the epithelial cells and reforms H+ and HCO3- ions via carbonic anhydrase
- then the HCO3- is reabsorbed via a Na-3HCO3 symporter (NBC family) in the basolateral surface
- some HCO3- is also reabsorbed directly from the lumen through another Na-HCO3- symporter on the apical (luminal) surface
H+ is NOT excreted, it’s recycled!!
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what does angiotensin II do in the proximal tubule?
angiotensin II directly stimulates Na+ reabsorption in the PCT, Henle’s loops, DR and collecting tubules by stimulating the following in the PCT:
- Na/K ATPase pump on the tubular epithelial cells basolateral membrane
- Na/H exchange in theluminal membrane, especially in the proximal tubule
- Na/HCO3 co transport in the baseolateral membrane
what happens to HCO3 in the thick ascending limb?
same mechanism as PCT
basolateral transporters: Cl−/HCO3−exchanger and K+/HCO3−cotransporter reabsorb HCO3 –> there’s also a Na/HCO3 cotransporter that is bringing HCO3 from the tissues into the epithelial cells which is reverse!
Na/H antiporter on the luminal surface where H+ goes into the lumen and Na+ goes into the epithelial cells
this section of the nephron is upregulated in acidosis and downregulated in metabolic alkalosis
where are the principal and intercalated cells?
they’re in the collecting duct and late distal tubule
they are mixed together
what happens to HCO3 in the distal tubules and collecting ducts?
type A or B intercalated cells will kick in depending on what you need
- HCO3- secretion in the Type B Intercalated cells in distal tubules
HCO3/Cl transporter is on the luminal surface and is pumping HCO3 into the lumen
H+ pump is on the basolateral surface pumping H+ into the tissues
- HCO3- reabsorption in the Type A Intercalated cells
HCO3/Cl transporter on the basolateral surface and it’s pumping HCO3 into the tissues
H+ pump is on the luminal surface and is pumping H+ out to the lumen
why do metabolic acidosis and hyperkalemia go hand in hand?
there’s an H+/K+ exchanger on the luminal surface of the type A intercalated cells in the distal tubules and collecting ducts
it pumps H+ into the lumen and K+ in
so when you have acidosis and you’re trying to secrete H+, you also absorb K+ so you get hyperkalemia too when you try yo get rid of the H+ ions!!
how are H+ ions excreted as NH4+ ions? where in the nephron does it happen?
this happens in the proximal tubule –> you excrete it as NH4 because you don’t want your urine to be so acidic or else it would really hurt
glutamine from protein metabolism in the liver is reabsorbed by endocytosis and then converted to
NH4+and HCO3- normally and then NH4+ ions are secreted into the lumen via NH4+/Na+ antiporter (instead of H+ ions via NHE3)
then HCO3- is reabsorbed via Na+/HCO3- cotransporter on basolateral surface
hypokalemia and acidemia stimulates ammoniogenesis**
Ang- II stimulates the basolateral Na+/HCO3- cotransporter
how is NH4 transported?
NH3 from the lumen is reabsorbed into the renal medullary interstitium and secreted again into the medullary collecting ducts and into the urine
each NH4+ excreted equivalent to one H+ excretion
the more acidic the tubular fluid, the faster and larger the NH3transfer.
what is the major buffer in urine?
phosphate
but most of your acid is excreted as NH4
66 year old man with amyotrophic lateral sclerosis is brough into the family clinic by his family who are concerned that recently he is extremely drowsy and always tired. during exam, he says he is having problems with morning headaches and doesn’t feel very refreshed when he wakes up.
ABG: 7.37 pH, HCO3 is 32, PCO2 is 47, PO2 is 70
electrolyte panel: Na+ is 130, Cl- is 98, HCO3 is 18
- does he have academia or alkalemia?
- is he compensating? how?
- chronic respiratory acidosis
- compensation because because kidney is compensating via increased HCO3 by:
- HCO3 reabsorption unregulated in PCT and TAL
- secretion of H+/generation of HCO3 in the DT and collecting ducts
how does the kidney secrete H+ and genernate HCO3?
two major mechanisms carried out by the tubular cells generate new HCO3- ions
both involve renal excretion of H+ ions:
- combined with bases (such as phosphates) or
- as NH4+ ions
this replaces the HCO3- lost when the acid load entered the body in acidosis
the net acid excretion of the kidneys is quantitatively equivalent to the amount of HCO3−generation by the kidneys
same mechanism in the luminal epithelial cell catalyzed by carbonic anhydrase
apical membrane H+-ATPase and H+/K+-ATPase transport H+ ions
HCO3- moves across the basolateral membrane mainly via the anion exchange (AE1 family) Cl/HCO3- antiporter in alpha-intercalated disks
minute quantities of H+ secreted as protons so that urine is not highly acidic
how is H+ excreted as a titrable acid?
in respiratory acidosis with excess H+ ions so H+ is removed and HCO3 is generated in the type A Intercalated cells of Distal tubular segments
high concentration of H+inside the cells (acidosis or hypokalemia) activate H+pumps
H2O + CO2 in the epithelium form H+ and HCO3- and H+ gets pumped into the lumen via H+/ATP pump while HCO3 gets reabsorbed into the tissues via the HCO3/Cl- pump which is how your body tries to compensate for the acidosis!!
in respiratory or metabolic acidosis,more H+ are pumpsinserted in the luminal membranes of the cells
then phosphate (HPO4-2) not filtered in the PCT binds to the H+ ions secreted into the lumen to form H2PO4- OR it can combine with NH3 to form NH4 and be excreted that way
aldosteronecan also increase H+/K+ ATPasepumps on luminal surface in alpha-intercalated cells to pump H+ into the lumen
a climber is coming down from Mt. evert. his ABG is drawn while breathing ambient air.
pH = 7.55, HCO3 = 12 PCO2 = 12, PO2 = 30
what does he have?
is he compensating? how?
respiratory alkalosis
his kidney is compensating because HCO3 levels are low:
- HCO3 reabsorption is down regulated int he PCT and TAL
- secretion of HCO3 ions in the DCT and collecting ducts in the type B intercalated cells
what are the transporters in type B intercalated cells?
same mechanism in the luminal epithelial cell catalyzed by carbonic anhydrase
HCO3- secreted via the HCO3/Cl pendrin antiporter on the luminal surface
H+ ions are reabsorbed via H+/ATPase on the baseolateral transporter
