9: Regulation of Acid-Base Balance Flashcards
Explain how/why the acid-base status affects proteins
Acid-base status is determined by the cc of H+ ions
Proteins contain titratable groups –> reversibly bind H+ ions –> deprotonate in response extracellular pH changes
–> changes the local charge density –> affecting proteins’ shape and biochemical behavior
Name 4 processes in the body that affect the plasma hydrogen levels
1) metabolism of ingested food
2) secretions of the GI tract
3) de novo generation of acids and bases from metabolism of stored fat and glycogen
4) changes in production and exhalation of CO2
What is a conjugate base?
the particular base formed when a given acid dissociates into a proton and a base
What is the isohydric principle?
acid and bases in solution are tied to one another beause they are exposed to and bind to the same hydrogen ion concentration
What are the most important buffer systems?
- phosphate
- proteins - albumin and hemoglobin
- CO2-bicarbonate buffer system
what are “fixed acids”?
fixed acids are non-volatile (e.g., acetic acid, lactic acid)
CO2 is a volatile acid - can evaporate
What is the conjugate base of CO2?
bicarbonate
Explain how these two equations differ
The first equation shows the classic Henderson-Hasselbalch equation without carbonic anhydrase but with the step of carbonic acid
the left part the equation would be very slow –> most tissues have carbonic anhydrase –> speeds it up and skips step of carbonic acid
Where are the chemoreceptors located that detect CO2 concentration?
- brain stem - central
- arterial - peripheral
How do the pancreatic and liver secretions affect the duodenal pH?
secrete large amounts of bicarbonate –> alkalinize
Compare the effects of metabolism of proteins, carbohydrates, and fats on the acid/base status
Proteins/Aminoacids
* depending on the protein/AA they can have alkalinizing or acidifcying effects
* e.g. sulfur-containing AA and ones with cationic side chains –> metabolized to CO2, H2O, urea –> end-result fixed acid, i.e., sulfuric acid –> quickly buffered to sulfate
* e.g., phosphorylated proteins –> phosphoric acid buffered to HPO42-
* e.g., amino acids with anionic side chains —> oxidative metabolism –> add base –> consumes H+
Carbohydrates and fat –> acid-base neutral under normal conditions
- anaerobic metabolism of carbohydrates –> lactic acid (fixed acid)
- metabolism of triglycerides to beta-hydroxybutyrate and acetoacetate –> ketone bodies (fixed aids
Explain why the lactate in LRS does not cause a lactic acidosis
LRS - contains the conjugated base of lactic acid -> will be oxidised to CO2 + H2O while taking up hydrogen ions + helps produce bicarbonate –> alkalizing/buffering
during lactic acidosis (e.g., circulatory shock), the body produces equal amounts lactate and hydrogen ions –> acidosis
where is most bicarbonate absorbed (name percentage as well)
proximal tubule - 80-90%
Describe the process of proximal tubular bicarbonate reabsorption
- basolater Na/K/ATPase pump –> decrease IC Na cc
- luminal Na/H - antiporter –> Na absorption IC and H+ excretion to lumen
- hydrogen ion reacts with bicarbonate (exallerated by carbonic anhydrase on the luminal cell surface) –> CO2 and H2O
- diffuses into cell via aquaporin 1 (AQP1) and through lipid bilayer
- CO2 in cell bind with water –> CA –> bicarbonate and H+
- H+ exits cell again via H+/ATPase and NaH-antiporter
- formed HCO3- –> leaves cell via Na-3HCO3 symporter
How much and by what mechanism is bicarbonate excreted in the loop of henle?
~ 10%
NHE3 antiporter
What are the two mechanisms by which bicarbonate can exit the tubular cells on the basolateral side?
depending on the location within the tubule:
* Cl-HCO3 antiporter
* Na-3HCO3 symporter
What tubular segment is responsible for responding to acid or base loads?
distal segments, specifically the collecting ducts
Explain how type B intercalated cells secrete bicarbonate
- Cl-HCO3- antiporter is located on the luminal instead of basolateral membrane
- H2O + CO2 in cell –> HCO3- + H+
- HCO3- secreted on liminal membrane
- H+ reabsorbed on basolateral membre via H+/ATPase
- Cl channel on basolateral membrane facilitating Cl movement
Explain how type A intercalated cells respond to an acid load
don’t just reabsorb/generate new HCO3-, but also secrete H+ that then binds to secreted bases to form undissociated acids to be urinated out
- IC CA forms H+ and HCO3-
- HCO3- moves out of cell on basolateral side via Cl-HCO3- antiporter (also called AE1)
- H+ moves out of cell on luminal side via (1) H-ATPase and (2) H-K-ATPases
How does phosphate facilitate renal acid secretion?
filtered divalent monohydrogen phosphate (HPO42-) –> binds free H+ in distal nephron –> enables excretion of H+ via monovalent dihydrogen phosphate
How do the kidneys handle glutamine?
- freely filtred
- taken up by the proximal tubules from (1) lumen and (2) from the interstitium via Na-glutamine symporters
- glutamine is then IC –> cells convert glutamine back to bicarbonate and NH4+
- NH4+ secreted into the lumen
- bicarbonate exits into the interstitium –> blood
Explain how the kidneys limit luminal ammonia/ammonium cc in the cortex?
The ammonium secreted into the proximal tubular lumen –> 80% is reabsorbed in the thick ascending loop of Henle via the Na-K-2Cl multiporter (Ammonium substituting for K) and then exiting into tinerstitium via Na-ammonium antiporter
–> net result = accumulation of ammonium in the medullary interstitium
this interstitial ammonium is again secreted in the medullary collecting ducts
* ammonium taken up from interstitium via Rh glycoprotein uniporters + some via Na-K-ATPase (ammonium substitiuting for K)
* ammonia secreted into the lumen via apical Rh glycoprotein
* combines with H+ in lumen (H+ was secreted via H-ATPase) –> ammonium
