Acid-base regulation Flashcards
What is the normal plasma pH?
7.35 – 7.45.
What are they two pH compensatory mechanism?
ACIDAEMIA NEEDS AN ALKALOSIS TO CORRECT; ALKALAEMIA NEEDS AN ACIDOSIS TO CORRECT.
- Changes in ventilation can stimulate a RAPID compensatory response to change CO2 elimination and therefore alter pH.
- Changes in HCO3- (base) and H+ retention/secretion in the kidneys can stimulate a SLOW compensatory response to increase/decrease pH.
SUMMARY: metabolic and respiratory acidosis/alkalosis.
Really good for reference.
What are the relative proportions of acid secretion in the lungs and kidneys?
LUNGS: 99%; KIDNEYS: 1%.
What is the normal plasma [H+]?
40 nmol/L.
What is the normal arterial bicarbonate concentration?
22-26 mEq/L.
What is the normal range of pH in the urine?
5-9.
Why is the normal urine pH range much wider than plasma pH range?
Because urine is the regulator of blood pH. So has large range in order to keep plasma pH constant.
How much bicarbonate is reabsorbed in the nephron, and in what proportions along the nephron? Why is so much reabsorbed?
80% reabsorbed in the PCT, 10% in ascending loop of Henle, 6% in DCT and 4% (if needed) in collecting duct. Usually, 100% is reabsorbed, because it is a HIGH CAPACITY CHEMICAL BUFFER that can respond RAPIDLY to changes in METABOLIC acid.
What is bicarbonate synthesised from?
CO2 – a volatile respiratory acid!
Why, in the context of bicarbonate concentration, is pH 7.4?
- Image shows Henderson-Hasselbalch equation which tells us the pH (the equation can also have H+ and H2O on the top and bottom respectively, since CO2 + H2O –> HCO3- + H+, but it is not important).
- If we substitute normal values for CO2 and HCO3-, and add pK (the dissociation constant), then pH becomes 7.4.
What does the Davenport diagram show?
Way of representing changes in arterial blood gas measurements/acid-base balance.
- Bottom = pH, top = [H+], y-axis = [HCO3-].
- We also want to add PCO2, but we have run out of axis, so we add another graph on top which maps PCO2 – it is very unorthodox as the graph has been bent round (PCO2 is on both axis) – otherwise, PCO2 scale would go off the chart. We have also made it non-linear to make it all fit – but the important stuff is the lower numbers anyway.
- Note that scale for [H+] is not linear – means graph is not huge.
- Green boxes show normal [H+]/pH range and normal HCO3- range. Green line represents normal PCO2 (of 5.3kPa). Where they all intersect, a circle Is drawn – this is the healthy zone.
How is metabolic acidosis/alkalosis represented on the Davenport diagram?
- In a METABOLIC ALKALOSIS, pH increases (moves right), HCO3- (because the alkalosis is METABOLIC) goes up. pH and HCO3- together gives the weird up and rightwards curve.
- In a METABOLIC ACIDOSIS, the opposite happens. The shape is shallower because of the way we have represented our PCO2.
- Note how these lines follow the PCO2 curves – this is because in metabolic acidosis/alkalosis, CO2 isn’t the thing that changes – it stays the same; so, the curves representing the change in pH mirror the CO2 curves also.
How is respiratory acidosis/alkalosis represented on the Davenport diagram? Sub-types?
- Only respiratory is split into chronic and acute because it is based on rate of breathing (acute = e.g. hyperventilation; chronic = e.g. long, slow changes in breathing).
- Base excess is calculated by distance from 24mmol/L.
- Chronic has a lot of overlap with the normal ranges for pH because for chronic acidosis/alkalosis where changes are slower, the body has time to make the physiological changes to restore normal conditions. This is why acute goes very wide.
- Chronic has greater change in HCO3: because of these compensatory mechanisms, HCO3- changes a lot more in chronic than acute. Remember, in respiratory alkalosis/acidosis, the changes in HCO3- is part of the compensatory response.
What is the process of HCO3- reabsorption?
- HCO3- + H+ converted into H2O and CO2 in the PCT.
- CO2 readily diffuses into PCT cell and recombines with H2O to form HCO3- and H+.
- H+ moves back into the PCT because we only want to retain HCO3-: it moves back via H+ ATPases and Na+/H+ antiporters.
- HCO3- is pumped out into the interstitum and peritubular capillary (part of the vasa recta) by Cl-/HCO3- exchangers, and Na+/HCO3- cotransporters (both retain the charge in and out of the cell).
- Na+ for Na+/H+ antiporter is maintained by the Na+/K+ ATPase on the basolateral surface.
- Cl- diffuses out via the basolateral surface for recycling back into the Cl-/HCO3- exchanger and maintain membrane potential in cell.
What is the mechanism of acid-secretion in the alpha cell?
ALPHA-CELL is acid-secreting because it saves HCO3- (and so, it is reabsorbed), and secretes lots of H+ into the filtrate.
- HCO3- is reabsorbed into the collecting duct cells.
- Na+/H+ anti-transporters, K+/H+ ATPases and H+ ATPases pump H+ back out into the tubule filtrate.
- HCO3- is moved out and into the blood by Cl-/HCO3- exchangers on the basolateral surface.
- Remember the Cl- diffusion from the Cl-/HCO3- exchanger.
What is the mechanism of HCO3-secretion in the beta cell?
BETA CELL is bicarbonate-secreting, so it secretes bicarbonate, and reabsorbs H+. It therefore has the same mechanisms as alpha-cells, just in opposing directions.
- Basolateral membrane contains H+ ATPases, Na+/H+ anti-transporters, K+/H+ ATPases.
- Apical membrane contains Cl-/HCO3- exchangers.
- Remember the Cl- diffusion from the Cl-/HCO3- exchanger.
How is HCO3- synthesised in the cuboidal epithelium of the PCT?
- Glutamine is split into ammonium and bicarbonate.
- The HN4+ is removed into the filtrate by NH4+/Na+ antiporters.
- HCO3- can then be reabsorbed into the peritubular capillary via the Cl-/HCO3- exchanger and 3HCO3-/Na+ cotransporter, coupled with the Na+/K+ ATPase.
What happens to the H+ ions pumped out and into the filtrate? (x2)
- H+ is pumped into the filtrate by H+ ATPase.
- Hydrogen phosphate in the filtrate is synthesised into H2PO4- (dihydrogen phosphate). This occurs during the HCO3- reabsorption across the nephron (collecting duct and PCT).
- OR, can bind to HCO3- to form carbonic acid.
