Acid/Base Flashcards
1
Q
How does the body control acid/base balance?
A
- The kidneys and the respiratory system work together to maintain acid/base balance.
- It is very important that the body controls H+ concentration in ECF, because sites on membrane proteins protonate and deportonate in response to changes in pH, effecting the behaviour of the proteins
- Maintainence of acid/base comes down to two processes
- Proper excretion of acid and base (respiratory and kidney)
- Maintaining buffer system
2
Q
How are plasma H+ concentrations altered?
A
- Metabolism of ingested food
- Secretions of GI tract
- Generation of acids and bases from metabolism of stored fat and glycogen
- Changes in production of CO2
3
Q
Acid/base equation
A
- Acid ⇌ conjugate base + H+
- [H+] = K[acid]/[base] k= dissociation constant
- pH = pKa + log[base/acid]
4
Q
Buffers
A
- Weak acids make up our buffers - buffers limit the change in pH that occurs if you add another acid or base
- Add acid = H+ released by that acid combines with the conjugate base restricting an increase in free H+
- Add base = the free H+ removed by the base are replaced by H+ the dissociates from the acid
- Remeber! Buffers do not eliminate acid or base from the body. They only limit their effects on blood pH
5
Q
Most important buffer system in the body
A
- CO2- bicarbonate buffer system
- CO2 acts like a weak acid (because it readily combines with water to form carbonic acid H2CO3)
- Carbonic acid dissociates into a proton and its conjugate base (bicarbonate)
- CO2 + H2O ⇌ HCO3- + H+
- Addings H+ is essentially equal to removing bicarbonate
- Concentration of CO2 stays pretty constant because respiratory rate is matched to metabolic production
- When H+ is added (or bicarbonate is removed) the body needs to generate new bicarbonate to replaced what was lost
6
Q
Renal transport of acids and bases - proximal tubule
A
- Kidneys filter over 4000mmol bicarb/day. Most of this is reabsorbed in the proximal tubule (80-90%) by the following mechanism
- Na/H antiporter secrets H+
- H+ in filtrate combines with filtered bicarb to form CO2 and H2O
- CO2 diffuses into the cell and combines with water to form H+ and HCO3-
- H+ produced from above reaction is secreted again and is excreted
- Bicarb is released into the insterstitum via Na/HCO3 symporter
- Glutamine inside the cell is metabolized to ammonium and HCO3-
- NH4+ is secreted and excreted
- HCO3- is reabsorbed
- Bicarb is reabsorbed by combining it with secreted H+ and turning it into CO2 and water, while simultaneously generating intercellular bicarb and transporting it to the interstitium
7
Q
Renal transport of acids and bases -Distal Tubules
Type A intercalated cells
A
- Type A intercalated cells
- Function in acidosis
- H+ is excreted (via ATPases on apical side) and HCO3- and K+ are reabsorbed
- New bicarb is formed from H2O and CO2 - it is NOT just reabsorption of filtered bicarb
- The H+ that is excreted in the urine attaches to bases (like phosphate) andis excreted. H+ must be excreted with non-bicarb base, or else it would just recombine with newly formed bicarb.
8
Q
Renal transport of acids and bases -Distal Tubules
Type B intercalated cells
A
- Type B intercalated cells
- Function in alkalosis
- HCO3- and K+ are excreted; H+ is reabosorbed (via ATPases on basolateral side)
9
Q
Kidneys response to base loads
A
- Kidneys reabsorb most of the filtered bicarbonate, but excrete just enough into the urine to match the input of base. The kidneys do this by:
- Allowing some of the filtered bicarb to pass through to the urine
- Secrete the bicarb via type B intercalated cells in the distal nephron (bicarb is excreted out and H+ is reabsorbed).
10
Q
Kidneys response to acid loads
A
- Generating bicarb from water and CO2 stimulaneously generates H+. So, H+ must be separated from the bicarb and excreted, or else the components will recombine and accomplished nothing. The kidneys do this by:
- Filtered bicarb is reabsorbed
- Kidney’s secrete additional H+ via ATPase in type A intercalated cells. This attaches to bases in tubular fluid other than bicarb and is excreted.
- Bicarb generated inside the cell is transported into the blood via CI-HCO3 antiporters, replacing the bicarb that was lost when acid entered the body
- H+ must be excreted as nonbicarb base, or else they would just recombine with newly generated bicarb.
11
Q
Acid excretion and Phosphate
A
- Phosphate is an important source of nonbicarb base allowing for the excretion of H+
- Free plasma phosphate exists as a mixture of weak acid and base. At a normal pH 80% of the filtered phosphoate is in base form. Most of the phosphate is reabsorbed at the proximal tubules, but some continues on to the distal nephron. As H+ are secreted, the remaining phosphate base takes up the secreted H+ and is excreted.
12
Q
Importance of ammonium in acid secretion
A
- Excretion of hydrogen ions as ammonium is very important in acid/base balance
- More H+ can be excreted via ammonium then via filtered bases
- Furthermore, filtered bases cannot be changed to serve the needs ot acid-base balance, but ammoniagenesis can be increases in response to acid loads (large acid loads are excreted mainly in form of ammonium.
13
Q
Glutamine and ammonium
A
- The amino acid glutamin can be thought of as containing the 2 components from which it was synthezied - base component (bicarb) and acid component (ammonium).
- The liver synthesizes more glutamine in response to low pH and proxmical tubules take up more gluamine in response to low pH (to increase bicarb production). High pH does the opposite
- Gluatmine is taken by proximal tubules cells where it is converted into bicarb and ammonium (NH4+). The ammonium is secreted into the lumen and bicarb is reabsorbed into the blood.
- If NH4+ is secreted you see net bicarb production
- If NH4+ is reabsorbed, it is metabolized by the liver back into urea and H+, consuming bicarb in te process. Result is no net bicarb production
14
Q
How do you quantify renal acid-base excretion
A
- Can quatify excretion of acid/base equivalents by looking at 3 quantities in urine
- Amount of titratable acidity - amount of acid taken up by urinary bases other than ammonium
- Amount of ammonium
- Amount of bicarb
- Net acid excretion = titratable acid excreted + NH4+ - bicarb excreted
15
Q
How does kidney regulate handling of acid and base loads
A
- Kidneys respond to acid-base loads by moving transporters for H+ and bicarb back and fortj between intracellular vesicles and surface membranes
- Acid loads = increase number of H-ATPases at apical membrane of A intercalated cells and increase CI-HCO3 antiporters on basolateral side
- Base loads = increase number of CI-HCO3 antiporters at apical membrane of B intercalated cells and increase H-ATPases on basolateral side
- Overtime acid/base loads can lead to conversion between A and B intercalated cells
- Adjustments are made in response to bicarb, pH, and PCO2
17
Q
Acid base disorders and compensation
A
- Generally, in acid/base disorders you expect to see compensation - i.e., when either pCO2 or bicarb levels change, the body changes the other variable in the same direction
- Compensation does NOT equal correction, because even if pH is returned to normal, both pCO2 and bicarb values are abnormal
18
Q
Approach to Acidosis
A
19
Q
Approach to Alkalosis
A
