PSL301: Water 7 Flashcards
Acid-base balance
Acid can ___ H+
donate
Base can ___ H+
accept
conversion between pH and [H]
pH = -log[H]
[H] = 10^(-pH)
normal pH in blood
- 4
7. 35 - 7.45 range
most acidic part of body
stomach (1.5 pH)
most basic part of body fluid
bile (pH = 8) alkaline urine (pH = 8)
effect of diet on pH
protein - acidic
- sulfur-containing AA are metabolized to H2SO4
sulfur containing AA
- cysteine
- methionine
1 Met or 1 Cys generates ___ H2SO4
1 mol
what prevents severe acidosis when we eat proteins?
buffers
BUFFERS
limit the change in [H] when an acid is added/removed from a solution
Buffers found in humans
- bicarb (HCO3-)
- phosphate (HPO4^2-)
- ammonia (NH3)
the bicarbonate buffer system is catalyzed by…
carbonic anhydrase (CA)
Why is the bicarb system so good?
both sides of the equilibrium can be independently regulated; no other buffer system has this quality
- this allows for compensation
Kidney has 2 effects on bicarb
- make new bicarb
2. reabsorb filtered bicarb
New bicarb is generated by excretion of…
H+, buffered by ammonia or phosphate
- NH4+
- H2PO4
How does kidney make new bicarb?
- CO2 + H2O -> H+ and bicarb
- H+ is secreted into lumen, buffered by ammonia/phosphate
- bicarb is exchanged with Na+, reabsorbed into bloodstream
Where does the phosphate we use to buffer come from?
- filtered from plasma
- diet
Mechanism of ammonia buffer system, from start to finish
- NH3 synthesized by proximal tubular cells
- Binds with H+, secreted into lumen as NH4+
- Reabsorbed in thick ascending limb
- NH3 diffuses through medulla
- Bind with H+ from MCD
- NH4+ trapped in CD lumen, excreted in urine
What is the more important urinary buffer? Why?
Ammonia;
- Phosphate amount is limited and cannot be adjusted
- Kidneys can regulate amount of ammonia 5-10x
ammonium is a weak ___
acid
___ freely diffuses across cell membranes & blood vessels
ammonia
___ does not readily cross cell membranes
ammonium
in a more acidic environment, there is more ammonia // ammonium
ammonium
How does ammonia buffer H+?
- Freely cross into lumen
- Bind H+ inside lumen
- NH4+ cannot cross back into tubular cell
- must be excreted
ammonia is synthesized by the…
proximal tubular cells from Glutamine
For every 1 H+ / 1 NH4+ secreted, ___ bicarb is synthesized
1
How is H+ secreted by the CD?
H+-ATPase
Which AA makes ammonia?
glutamine
What regulates ammonium excretion?
acid/base status
- acidosis = ammonia synthesis & H+ secretion in CD (activate H+-ATPase)
Cell pH is recognized by ____, which then alters cell function to _____
cell receptors;
normalize pH
When is ammonium excretion increased?
- metabolic & respiratory acidosis
- higher protein intake
when there is a large acid load, ammonium excretion can increase ____ fold, but it takes ___ days to reach maximum
5-10;
3-5
reabsorption of bicarb happens at…
proximal tubule
the best place to reabsorb large amounts of solute is at…
proximal tubule
main proximal tubule Na transporter
Na-H exchanger (NHE3)
for every 1 H+ secreted, ___ bicarb is reabsorbed
1
What is the drive for excreting H+ at the proximal tubule?
Na-K ATPase keeps intracellular Na+ low, so NHE3 pumps Na+ into cell in exchange for H+ into lumen
Difference in mechanism between bicarb reabsorption & regeneration?
regeneration: CO2 is from capillary
reabsorption: CO2 is from lumen
most common acid-base disorder is…
metabolic acidosis
3 ways which metabolic acidosis can occur
- addition of an acid not normally present
- kidney can’t secrete ammonium
- loss of bicarb through diarrhea
Which acids cause metabolic acidosis?
- lactic acid
- diabetic ketoacidosis
- methanol poisoning (formic acid)
- ethylene glycol poisoning (antifreeze)
- salicylate poisoning (aspirin)
excess lactic acid may be the result of…
anaerobic glycolysis
- exercise
- shock (tissue not oxygenated)
- liver failure (removes lactate)
formic acid can’t be metabolized to…
CO2 and H2O
ethylene glycol is very dangerous because…
it forms poisonous metabolites
Why does lactic acidosis happen when there is not enough oxygen?
- build up of pyruvate
- increased glycolysis to supply ATP
- increase in NADH that want to be used up (minor effect)
Why might cardiac shock result in anaerobic respiration?
not enough O pumped by heart
causes of lactic acidosis
- low CO (shock)
- hypoxemia
- severe anemia
- exercise
- drugs that interfere w/ mitochondrial action
- liver failure
site of lactate metabolism
liver
what happens if there is no respiratory compensation for metabolic acidosis / alkalosis?
then there is also respiratory acidosis / alkalosis
If toxic alcohols are present in blood stream, how do we cure it?
hemodialysis (has to be early enough)
main role of kidney in acid-base balance
maintain normal blood bicarbonate
kidney excretes ___ in order to make new bicarb lost to buffering
ammonium
the body responds to acid load by…
- buffer with bicarb (rapid)
- hyperventilating to lower pCO2 (rapid)
- excrete more ammonium (slow)
