Lecture 8: Control of plasma pH Flashcards
What are the 2 major organ systems involved in the maintenance of acid-base homeostasis?
Respiratory system: lungs are rapid responders (change breathing)
-primarily controls CO2
Urinary system: kidneys help with longer term homeostasis (full compensation could take days)
-primarily controls HCO3-
Both essential
What is plasma pH regulated by?
Very low concentration of H+ ions, but these are tightly regulated
-44.5-35.5 nmol/l
(pH 7.35-7.45)
Which is more dangerous: alkalosis or acidosis?
Alkalosis
- lowers free calcium by causing Ca2+ ions to come out of solution and bind elsewhere
- this increases neuronal excitability (bivalent cations: charge sheilding, which protects the membranes from becoming too excitable)
- leads to paraesthesia and tetany
45% mortality: pH rises to 7.55
80% mortality: pH rises to 7.65
What is the problem with acidosis?
- increase in plasma potassium ion conc
- this effects excitability: cause arrythmias
- increase in H+ ions also effects enzymes: denatures proteins and effects muscle contractility, glycolysis, hepatic function
Effects severe below pH 7.1
Life threatening below pH 7.0
How do the lungs and kidneys work together to control plasma pH?
Kidneys: control pH- variable recovery of HCO3- and active secretion of H+ ions
Lungs: alveolar ventilation controls pO2 and pCO2, and the rate of ventilation is controlled by chemoreceptors
Where is HCO3- made?
HCO3- is made in the RBC’s
-conc is controlled by the kidneys
Normal conc in arterial blood is: 25 mmol/l
Range: 22-26
But can be changed to maintain pH
What do we produce due to metabolism?
Acid in the form of H+ ions (continuous production)
- react with HCO3- to form CO2 and water
- HCO3- does not deplete because:
- the kidneys recover all filtered HCO3-
- proximal tubule makes HCO3- from AA’s, putting NH4+ into the urine
- distal tubule makes HCO3- from CO2 and H2O, and the H+ is buffered by phosphate and ammonia in the urine
What is the renal control of HCO3- in the proximal tubule?
- HCO3- is filtered at the glomerulus
- most is recovered in the PCT
- CO2 and H2O in the tubular cell as they are metabolically active and these are converted to H+ and HCO3- in the cell, creating high conc of H+ for the Na/H exchanger
- the HCO3- are pumped into the ECF via the Na/HCO3- symporter
- Na/K ATPase on basolateral side of tubular cell pumps Na+ out and K+ in
- this creates a sodium gradient allowing the Na/H exchanger to pump Na into the cell and H+ out of the cell
- H+ reacts with HCO3- in the lumen to form H2O and CO2
- CO2 diffuses into the tubular cell
Via this 80% of HCO3- is recovered
How is HCO3- created in the proximal tubule?
- glutamine is converted to NH4+ and alpha-ketoglutarate
- ammonium (NH4+) dissociates into NH3 (ammonia) and H+
- NH3 is uncharged so can freely diffuse out of the cell into the lumen
- in lumen it combines with the H+ from the Na/H exchanger to form NH4+, which buffers the H+ ions
- alpha-ketoglutarate breaks down into two HCO3- which are moved out into ECF via Na/HCO3- symporter
What happens to HCO3- in the distal tubule and where does this occur?
Occurs in the alpha-intercalated cells
- CO2 and H2O react in the cell to form H+ and HCO3-
- distal tubule and collecting ducts secrete H+ produced from reaction of CO2 and H2O
- these are actively secreted via H+ ATPase
- H+ is buffered by ammonia (this can freely move from the PCT) and phosphate to produce NH4+ and H2PO4- which are excreted as they are charged (trapped in lumen)
- HCO3- leaves via HCO3-/CL- exchanger on basolateral membrane
Why do we excrete ammonium in our urine?
Major adaptive response to an increased acid load in healthy individuals due to metabolism
-ammonium generation from glutamine in PCT can be increased in response to low pH
What is the minimum pH of urine and why doesn’t it get any lower than that?
- 5
- not lower due to the buffering system (ammonium and hydrogen phosphate buffering systems)
- no HCO3- in urine
How much H+ do we excrete per day?
50-100 mmol
-needed to keep HCO3- normal
What are reciprocal ion shifts?
happens in cells throughout the body
Acidosis: -K+ moves out of the cells -H+ move into the cell =hyperkalaemia and decreased K+ excretion in distal nephron
Alkalosis:
-K+ moves into cells
-H+ move out of cells
=hypokalaemia and enhanced excretion of K+ in distal nephron
How does hyperkalaemia disturb the acid base balance?
Hyperkalaemia makes intracellular pH of tubular cells more alkaline
-H+ ions moves out of cell as K+ moves into cell down its conc gradient (this tends to favour HCO3- excretion)
=metabolic acidosis
How does hypokalaemia disturb the acid base balance?
Hypokalaemia makes the intracellular pH of tubular more acidic
-H+ ions move into cells
-this favours H+ excretion and HCO3- recovery
=Metabolic alkalosis
What is respiratory acidosis?
-hypoventilation
-hypercapnia (high pCO2)
-causes a fall in plasma pH
(normal HCO3-)
What is respiratory alkalosis?
-hyperventilation
-hypocapnia (fall in pCO2)
-rise in pH
(normal HCO3-)
What is compensation?
Plasma pH depends on the ratio of HCO3- to pCO2
-therefore changes in pCO2 can be compensated by changes in HCO3-
-kidneys increase HCO3- to compensate for respiratory acidosis
-kidneys decrease HCO3- to compensate for respiratory alkalosis
This takes time (2-3 days)
What is compensatory respiratory acidosis characterised by?
- high pCO2
- raised HCO3-
- normal pH
What is compensatory respiratory alkalosis characterised by?
- low pCO2
- lowered HCO3-
- normal pH
What is metabolic acidosis?
- tissues produce acid abnormally, this reacts with and removes HCO3-, producing CO2 and water
- CO2 breathed off at lungs so there is no increase in arterial pCO2
- fall in HCO3-
- fall in pH
What is the anion gap?
Used to determine the cause of metabolic acidosis (measured in an ABG)
-difference between measured cations and anions
((Na+) + (K+)) - ((Cl-) + (HCO3-))
-normally 10-18 mmol/l because there are other anions present
When would you get an increase in the anion gap?
If metabolic acid reacts with HCO3-, the anion of the acid replaces the HCO3-, and this is not a measured anion, therefore the anion gap increases.
If the HCO3- is replaced by Cl- ions, then you won’t get a change in the anion gap
(in renal causes of acidosis the anion gap will remain unchanged, as you aren’t making enough HCO3-, but this is replaced by Cl-)
