What is the normal range of plasma pH?
7.38 - 7.42
What are the major clinical effects of Alkalaemia?
Lowers free Ca2+ in serum:
Increases excitability of nerves
If greater than 7.45:
Tetany (Involuntary muscle contraction, danger to breathing)
What are the mortality rates of Alkalaemia at pH 7.55 and 7.65?
45% at 7.55
80% at 7.65
What are the major clinical effects of Acidaemia?
Increase plasma potassium
Reduced cardiac and skeletal muscle contractility
Reduced glycolysis in many tissues
Reduced hepatic function
Effects sever below 7.1 and life threatening below 7.0
How is plasma pH determined? What systems are involved?
Dependent on pCO2 to [HCO3-] ratio
pCO2 determined by respiration
[HCO3-] determined by kidney
What causes respiratory acidaemia and alkalaemia?
Hypoventilation leads to hypercapnia, causing plasma pH to fall
Hyperventilation leads to hypocapnia causing plasma pH to rise
Explain briefly the role of chemoreceptors in pH balance
Keeps pCO2 within tight limits
Corrects disturbances in pH with respiratory changes
Enable changes in respiaration driven by changes in plasma pH
Explain the role of the kidneys in correcting respiratory driven pH changes
Kindey control [HCO3-] and hence can conpensate for change in pCO2 with change in [HCO3-]
Respiratory acidaemia can be compensated by increase in [HCO3-] (Compensated respiratory acidaemia)
Respiratory alkalaemia can be compensated by decrease in [HCO3-] (Compensated respiratory alkalaemia)
Describe metabolic acidaemia and it's compensation
Tissues produce acid (E.g. H+) that reacts with HCO3-
This leads to a fall in plasma pH
Also produces an anion which can replace HCO3-
Compensation via change in ventilation:
Increased ventilation lowers pCO2
Restores normal pH (ideally)
Describe metabolic alkalaemia and its compensation
Plasma [HCO3-] rises (E.g. post-vomiting)
Leads to rise in plasma pH
Compensation via ventilation change:
Decrease in ventilation can only partially compensate
Briefly describe renal control of [HCO3-]
Large quantities filtered per day (4500mmol)
Should be able to lose HCO3- very easily
To increase [HCO3-] must both recover all filtered and make new
How does the kidney produce HCO3-?
Normal metabolic activity:
CO2 + H2O = HCO3- + H+
HCO3- enters plasma
H+ excreted in urine
HCO3- can be produced from amino acids, this produces NH4- to enter urine
From where in the kidney tubule is HCO3- recovered?
80-90% in PCT
Rest in Tal of LoH
Describe the reabsorption of HCO3- from the kindey lumen
Basolateral Na+/K+ ATPase produces Na+ gradient across luminal membrane
Gradient allows Na+/H+ exchanger to pump H+ out of cell and Na+ in
H+ reacts with HCO3- in the lumen
HCO3- + H+ = H2O + CO2
H20 and CO2 are reabsorbed and react
H20 + CO2 = HCO3- + H+
HCO3- is reabsorped through basolateral membrane
H+ is recycled
How is HCO3- produced via the mechanism specific to the proximal tubule?
Glutamine is broken down to produce Alpha-Ketoglutarate and NH4-
Alpha-Ketoglutarate makes 2 HCO3-
HCO3- into ECF
NH4- into lumen
How does the kidney produce HCO3- via a mechanism specific to the DCT?
Metabolic CO2 reacts with H20 to produce HCO3- and H+
HCO3- secreted into ECF
Na+ gradient insufficient to drive H+ secretion into lumen
Active secretion of H+ used instead
H+ in lumen buffered by filtered phosphate and excreted ammonia
What is the total acid excretion per day in the kidneys?
In what form is H+ found in the urine?
50-100mmol of H+
Some H+ buffered by phosphate, the rest attached to ammonia
How is H+ excretion controlled?
Probably by changes in tubular cell's intracellular pH
This pH change is the concequence of changing rates of [HCO3-] export
Therefore control of H+ is acheived through control of [HCO3-]
How might respiratory function lead to a change in H+ excretion?
Respiratory acidaemia/alkalaemia will affect intercellular pH in the renal tubule due to changes in CO2 diffusing in as pCO2 is altered
This will produce an increase/decrease in HCO3- export to plasma and hence increase/decrease H+ excretion
How does [K+] affect pH of plasma?
[K+] affects HCO3- reabsorption and ammonia excretion
E.g. [K+] rise leads to decreased capacity of the kidney to reabsorb and create HCO3-
Hypokalaemia can therefore lead to metabolic alkalosis
Hyperkalaemia can lead to metabolic acidosis
Outline the renal cellular responses to acidosis
Enhanced H+/Na+ exchange (Fully recover filtered HCO3-)
Increase NH4- production in PCT
Increased H+ ATPase in DCT
All lead to an increased capacity for the renal cells to produce and export HCO3- and correct acidosis
Explain the Anion Gap
Difference between ([Na+] + [K+]) and ([Cl-] + [HCO3-])
Indicates whether HCO3- has been replaced with something other than Cl- (ie. unaccounted ions)
Increased if anions from metabolic acids have replaced plasma HCO3-
Sometimes renal problems can reduce [HCO3-] and not increase the anion gap as the HCO3- has been replaced with Cl-
Describe the kidney response to metabolic alkalosis
When might problems arise with correction?
[HCO3-] increases after persistent vomitting
HCO3- infusions can be corrected extremely rapidly as rise in intracellula pH in the renal tubule leads to decreased H+ secretion and hence HCO3- recovery
If there is also volume depletion, Na+ conservation is prioritised
High rates of Na+ reabsorption raise H+ excretion, favouring HCO3- recovery
This limits our ability to excrete HCO3-
Describe the kidney's response to respiratory alkalosis
Rise in tubular pH due to lower pCO2 induce less HCO3- export by reducing H+ secretion into lumen (hence reduing HCO3- recovery from lumen)
HCO3- is therefore excreted and [HCO3-] falls to correct the [HCO3-]/pCO2 ratio
Give the reference ranges for:
pH = 7.38 - 7.42/7.46
pCO2 = 4.2 - 6.0 kPa
[HCO3-] = 22 - 29 mmol.l-1
pO2 = 9.8 - 14.0 kPa
What are the would you expect an increase or decrease in the values given below in uncompensated metabolic acidosis?
What are the would you expect an increase or decrease in the values given below in compensated metabolic acidosis?
Normal or Low
What are the would you expect the values given below to be low, high or normal in uncompensated metabolic alkalosis?
What are the would you expect the values given below to be low, high or normal in compensated metabolic alkalosis?
What are the would you expect the values given below to be low, high or normal in uncompensated respiratory acidosis?