Acid-Base Balance Flashcards
What should the pH of plasma be?
7.35-7.45
What happens if a patient has alkalaemia?
Alkalaemia lowers free calcium by causing Ca2+ ions to come out of solution.
It can lead to paraesthesia and tetany (seizures)
It is worse than acidaemia: if pH is above 7.55 then mortality is 45%, if pH is over 7.65 then 80% mortality!
What is acidaemia?
Increases in plasma potassium ion concentration effects excitability of cells - particularly cardiac muscle which can lead to arrhythmias.
Also, increasing [H+] affects many enzymes —> denatures proteins —> effects muscle contractility, glycolysis, hepatic function
The effects are severe it pH falls below 7.1 and life threatening if below 7.0
Describe the buffer system
Dissolved CO2 reacts with water to form H+ and HCO3- (reversible)
Net direction depends on the concentrations of reactants and products
pH depends on how much CO2 reacts to form H+
- [CO2] dissolved pushes reaction to the right
- [HCO3-] pushes reaction to the left
What does plasma pH depend on?
The ratio of [HCO3-]:pCO2
PCO2 is determined by respiration
- Controlled by chemoreceptros
- Disturbed by respiratory disease
[HCO3-] determined by the kidneys
- Controlled by the kidneys
- Disturbed by metabolic and renal disease
How do the kidneys control pH?
They can vary the recovery of HCO3- and the active secretion of H+
(Kidneys take time to adjust to change in pH)
How do the lungs control pH?
Alveolar ventilation allows diffusion of oxygen into blood and CO2 out of blood - controls pO2 and pCO2
Rate of ventilation is controlled by chemoreceptors
What is the pH of arterial blood determined by?
Ratio of pCO2:[HCO3-]
HCO3- made in RBCs BUT the concentration present is controlled by the kidneys.
Normal [HCO3-] is 22-26mmol/l but it can be changed to maintain pH.
Why does the acid produced due to metabolism not deplete HCO3-?
The kidneys recover all filtered HCO3-
Proximal tubule makes HCO3- from amino acids, putting NH4+ into urine
Distal tubule makes HCO3- from CO2 and H2O; the H+ is buffered by phosphate and ammonia in the urine.
Describe the renal control of HCO3-
HCO3- filtered at the glomerulus
Mostly recovered in PCT
H+ excretion linked to Na+ entry in PCT
H+ reacts with HCO3- in the lumen to form CO2 which enters cell
Converted back to HCO3- which enters ECF
How do the proximal tubules make HCO3-?
Glutamine is broken down into a-ketoglutarate
- Produces HCO3- and NH4+
- HCO3- enters ECF
- NH4+ enters lumen (urine)
How do the DCT and CD control HCO3-?
DCT and CD secrete H+ produced from reaction of CO2 with water.
H+ ions are actively secreted
H+ buffered by ammonia and phosphate to make products which are excreted
No CO2 is formed to re-enter the cell
Allows HCO3- to enter plasma.
How does ammonia help to control HCO3-?
Ammonia = important response to control acid load
Ammonium generation from glutamine in PCT can be increased in response to low pH.
- NH3 freely moves into lumen and throughout the interstitium
- H+ actively pumped into lumen in DCT and CD
- H+ combines with ammonium to make ammonium
- NH4+ can also be taken up in TAL and transported to insterstitium and dissociates to H+ and NH3 - lumen of collecting ducts.
What is the minimum pH of urine?
4.5
Why will there be no HCO3- in the urine?
It has all been recovered by the kidney. There is H+ though.
Some H+ buffered by phosphate.
Some has reacted with ammonia to form ammonium
Why does acidosis cause hyperkalaemia?
In response to inwards movement of H+, there is an outward movement of k+ ion.
This decreases the potassium excretion in the distal nephron.
Why does alkalosis cause hypokalaemia?
Potassium ions move into cells in repose to H+ moving out.
Enhanced excretion of K in the distal nephron.
(Ca is the main issue in alkalosis though)
How can hyperkalaemia lead to alkalosis and hypokalaemia lead to acidosis?
Hyperkalaemia makes intracellular pH of tubular cells more alkaline as:
- H+ ions move out of the cells
- This favours HCO3- excretion therefore causing metabolic acidosis
Hypokalaemia makes the intracellular pH of tubular cells more acidic
- H+ ions move into the cells.
- This favours H+ excretion and HCO3- recovery therefore causing metabolic alkalosis.
How does ventilation disrupt acid base balance?
Hypoventilation —> Hypercapnia (pCO2 rise) —> fall in plasma pH —> respiratory acidosis
OR
Hyperventilation —> hypoventilation (pCO2 fall) —> rise in pH —> respiratory alkalaemia
PH goes in opposite direction of pCO2
List the Characteristics of hypercapnia
High pCO2
Normal HCO3-
Low pH
List the characteristics of hypocapnia
Low pCO2
Normal HCO3-
Raise pH
How does the kidney compensate for respiratory changes?
Kidneys increase [HCO3-] to compensate for respiratory acidosis and decrease for alkalosis to get the ratio of pCO2:[HCO3-] similar.
But, this can take 2-3 days.
What are the characteristics of compensatory respiratory acidosis?
High pCO2
Raised [HCO3-]
Relatively normal pH
What ate the characteristics of compensated respiratory alkalosis
Low pCO2
Lowered [HCO3-]
Relatively normal pH
How does metabolic acid cause a metabolic acidosis?
Acid - reacts with and removes HCO3-
This results in a fall in [HCO3-] which causes a fall in pH
This metabolic acidosis
What is the anion gap?
This is the difference between the measured cations and measured anions.
[Na+]+ [K+]) - ([Cl-] + [HCO3-])
Normal gap is 10-18mmol/L as not measuring all the anions.
This gap is increased in HCO3- is replaced by other anions.
If a metabolic acid (e..g lactic acid) reacts with HCO3-, the anion of the acid replaces HCO3-.
What will renal / metabolic acidosis to do the anion gap?
Metabolic causes increase the anion gap as the HCO3- is replaced by another organic anion from an acid.
In renal causes of acidosis anion gap will be unchanged - as despite not making enough HCO3, it is replaced by Cl-.
What are the characteristics of compensating metabolic acidosis
Peripheral chemoreceptors (carotid bodies) detect drop in pH. This stimulates ventilation which leads to a decrease in pCO2.
Therefore it is characterised by:
- Low HCO3-
- Lowered pCO2
- Nearer to normal pH.
What is metabolic alkalosis?
If [HCO3-] increases, this is metabolic alkalosis.
Therefore, will have:
- Normal pCO2
- Raised HCO3-
- Increased pH
Cannot normally be compensated to a great extent by reducing breathing - need to maintain pO2
Should be easy for kidneys to correct
What conditions lead to respiratory acidosis?
Type 2 respiratory failure:
- Low pO2 and high PCO2
- The alveoli cannot be properly ventilated
- Severe COPD, Severe asthma, drug overdose, neuromuscular disease
It can be compensated for my increase in [HCO3-] - in chronic conditions, it is usually well compensated for so that pH is near normal.
What conditions can lead to respiratory alkalosis?
Hyperventilation:
- Anxiety / panic attacks - acute settings
- Low pCO2, rise in pH
Hyperventilation in response to long-term Hypoxia - Type 1 respiratory failure.
- Low pCO2 with initial rise in pH
- Chronic hyperventilation can be compensated for by fall in [HCO3-]
- Can restore pH to near normal.
What condition can lead to metabolic acidosis with an increased anion gap?
If anion gap in INCREASED - indicates a metabolic production of an acid.
- Ketoacidosis - diabetes
- Lactic acidosis - exercising to exhaustion, poor tissue perfusion
- Uraemic acidosis - advanced renal failure - reduced acid secretion, build up of phosphate, sulphate and urate in the blood.
What conditions can lead to metabolic acidosis with a normal anion gap?
Normal - HCO3- is replaced by Cl-
Renal tubular acidosis (rare)
- Problems with transport mechanisms in the tubules
- Type 1 (distal) RTA - inability to pump out H+
- Type 2 (proximal) RTA (very rare) - problems with HCO3- reabsorbtion.
Severe persistent diarrhoea can also lead to metabolic acidosis due to loss of HCO3-
- Replaced by Cl-
- Therefore anion gap unaltered.
What effect does metabolic acidosis have on potassium?
Cause increased reabsorbtion of K+ by the kidneys and movement of K+ out of cells. (Hyperkalaemia)
However in diabetic ketoacidosis may be a total body depletion of K+.
- K+ moves out of cells (due to acidosis and lack of insulin)
- BUT osmotic diuresis means K+ lost in urine
What conditions can lead to metabolic alkalosis?
In alkalosis - HCO3- is retained in place of Cl-
Stomach is a major site of HCO3- production
- By-product of H+ secretion
- Severe prolonged vomitting -loss of H+
- Mechanical drainage of the stomach
Also:
- Potassium depletion / mineralcoticoid excess
- Certain diuretics (loop and thiazide)
Summarise metabolic alkalosis
HCO3- increase e.g. after persistent vomiting -This should be very easy to correct. HCO3- can be excreted very rapidly following infusion of HCO3-
Corrected by:
-Rise in pH of tubular cells leads to fall in H+ excretion and reduction in HCO3- recovery
BUT
Problems if there is also volume depletion
-Capacity to loose HCO3- is reduced because of high rate of Na+ recovery
-Recovering Na+ favours excretion and HCO3- recovery.
What effect does metabolic alkalosis have on potassium?
Less H+ excretion in nephron leads to more K+ excreted.
Alkalosis also causes movement of K+ ions into cells.
This leads to hypokalaemia
What changes will you get in respiratory acidosis or alkalosis?
PCO2 not normal, [HCO3-] is normal and pH has changed in opposite direction to pCO2.
What changes will you get in metabolic acidosis or alkalosis?
[HCO3-] is not normal, pCO2 is normal and pH has changed in the same direction as [HCO3-].
What values do you get if it is compensatory respiratory acidosis?
High pCO2
[HCo3-] is raised
pH is relatively normal
If [HCO3-] is low, pCO2 is low, pH is normal, what could be wrong?
Compensatory respiratory alkalosis or compensated metabolic acidosis
Check respiratory disease or altitude exposure and anion gap to work out what it is.
