Pulmonary Physiology Week 0.5 Flashcards
Describe the types of acids the body must deal with to maintain a mildly alkaline pH.
Large load of volatile acid (CO2–> carbonic acid) and a much smaller, more difficult load of non-volatile acid (H2SO4 from protein)
What is the normal pH of the body?
7.4
_______ the first line of defense against an acid load
Chemical buffering
______ is the second line of defense against an acid load
Regulation of CO2 levels by the lungs
_______ is the third line of defense against an acid load
Regulation of fixed (metabolic) acid and bicarbonate by the kidneys
Describe the four ways in which kidneys maintain physiological pH
1) conserve filtered bicarb; 2) make new bicarb to replace lost bicarb; 3) excrete xs bicarbonate in alkalosis; 4) excrete fixed acid
How do the kidneys excrete fixed acid?
Turn carbonic acid into new bicarb (which is reabsorbed) and H+ (which is excreted).
Where does the majority of bicarbonate reabsorption occur? (when pH is less than 6)
80% occurs in the proximal convoluted tubule
In what areas is bicarbonate reabsorbed? (when pH is less than 6)
15% in the thick ascending limb of LOH and 5% in the cortical collecting duct/distal tubules
[according to guyton-hall - all parts except for thin limbs of LOH]
For each bicarbonate reabsorbed, what must be secreted?
One H+!!!!!!
Describe the process by which CO2 drives bicarbonate reabsorption in the proximal tubules.
CO2 either diffuses into tubular cell or is created within the tubular cell then joins with H2O to form carbonic acid [reaction driven by carbonic anhydrase]. Carbonic acid then dissociates into bicarbonate and H+. Bicarbonate is reabsorbed into interstitial fluid whereas H+ is secreted into the the tubular lumen via Na/H antiporter
Describe the process by which bicarbonate is reabsorbed from the lumen.
The lumen is not permeable to bicarbonate, therefore bicarbonate joins with secreted H+ to form carbonic acid in the lumen. The carbonic acid then dissociates to form CO2 and H2O. CO2 diffuses into the tubular cell then recombines with H2O to form new carbonic acid –> new bicarb –> reabsorbed into interstitial fluid
Whenever an H+ is formed in the tubular epithelial cells, what happens?
An HCO3- is formed and released back into the blood! Reabsorption of bicarb yay!
Does reabsorption of bicarbonate from the tubular lumen result in net secretion of H+?
No, because the H+ that is secreted is used to form carbonic acid then CO2 and H2O and blah blah blah
What are the two types of epithelial cells located in the distal nephron/collecting duct? Which secrete acid?
Principal cells (65%) and alpha-intercalated cells (35%). Alpha-intercalated cells secrete acid.
Why is bicarbonate reabsorption an ATP driven process?
tubule can be highly acidic on inside (down to 4.4) so need energy so secrete H+ ions into lumen.
How is energy for H+ secretion into tubular lumen derived in the proximal tubule, LOH, and early distal tubule?
The Na/K ATpase on the basolateral membrane establishes a Na+ gradient [Na+ reabsorbed into interstitial space]. This provides the energy for the Na/H antiport on the apical membrane [facing the tubular lumen], so Na+ reabsorbed and H+ secreted into lumen
What are the two major differences in bicarbonate reabsorption in the intercalated cells of the late distal tubule/CCT in comparison to other areas of the nephron?
1) H+ is secreted into lumen via ATP-driven transporter [in other parts, via Na+/H+ secondary active transport]
2) Carbonic anhydrase is not found on the apical membrane of alpha-intercalated cells
What happens to bicarbonate in an alkalotic patient?
In an alkalotic patient, increased bicarbonate in the lumen leads to increased excretion of bicarbonate and increased urine pH. All of the H+ is used up, so only a maximal amount of carbonic acid can be formed to recycle into tubular cells and back into body, so remaining HCO3- is excreted.
What is the function of carbonic anhydrase?
Carbonic anhydrase drives the formation of carbonic acid from H2O and CO2.
Why are carbonic anhydrase inhibitors such as Diamox used?
To relieve alkalosis quickly such in the case of mountain sickness. Prevent bicarbonate reabsorption from the kidney by preventing the formation of carbonic acid, an intermediary step in the process. Therefore, more bicarbonate is excreted and pH returns to normal.
Why does mountain sickness cause alkalosis?
When you are at a high elevation, there is a decrease in PO2 so you breathe more rapidly, therefore expire more CO2, which leads to respiratory alkalosis
What is a problematic side effect of carbonic anhydrase inhibitors such as Diamox?
Bicarbonate excretion also boosts Na+ excretion which leads to osmotic diuresis and then dehydration.
How does bicarbonate excretion (decrease in absorption) such as seen in carbonic anhydrase inhibitors boost Na+ excretion?
Na+ is normally reabsorbed from the lumen via the Na+/H+ antiport in the proximal tubule. However, if a carbonic anhydrase inhibitor used, then less CO2 enters tubule cells, so less bicarbonate and H+ are made, so the H+ antiporter does not uptake much Na+.
What are the two ways by which the kidney eliminates fixed acid?
1) formation of titrateable acid; 2) formation of ammonium (NH4+)
_________ is the predominate titrateable acid in tubular fluid
Phosphate (PO4 3-)
Describe the titration curve of phosphate.
If pH decreases, phosphate will pick up H+ and make H2PO4-. As pH increases, phosphate will pick lose H+ and will have HPO4 2-.
In normal body pH, which form of phosphate is more common?
HPO4 2-
Describe the formation of titrateable acid in the lumen.
After the transport maximum for phosphate is reached, the phosphate that remains in the lumen combines with excess H+ to form H2PO4-. This stabilizes the pH in the urine and then H2PO4- is excreted as a sodium salt.
How is excretion of large amounts of H+ in the urine accomplished (2 molecules)?
via phosphate and ammonium buffers
Whenever an H+ secreted in the tubular lumen combines with a buffer other than bicarbonate, where is there a net gain?
Net gain in bicarbonate. In the tubular cell, bicarbonate and H+ are formed together. Since the H+ formed is being excreted, there is a net gain of bicarbonate returning to body (no longer a replacement)
Why is most buffering done via the ammonium system rather than the phosphate system?
Under normal conditions, most phosphate is reabsorbed, so only limited quantity available for buffering
Glutamine is transported into the proximal tubular cells where it is metabolized to form what two molecules?
2 NH4+ (ammonium) and 2 HCO3- (bicarbonate)
What happens to the ammonium and bicarbonate that is formed from glutamine metabolism in the proximal tubule?
Ammonium is secreted into the tubular lumen via antiport with sodium (sodium reabs). The bicarbonate is then reabsorbed into interstitial fluid(back to body) with the Na+.
Basically, for each molecule of glutamine metabolized in the proximal tubules, two NH4+ molecules are ______ and two HCO3- molecules are ______.
secreted into the urine, reabsorbed into this blood.
How does the ammonium buffering system work in the collecting tubules?
H+ is secreted via ATPase on apical membrane of tubular cell. The H+ combines with NH3 to form NH4. The tubular cell membrane is permeable to NH3 but not NH4+ therefore NH4+ is trapped and is excreted. As usual, for each H+ secreted, there is an HCO3- reabsorbed.
