Lec 9 - Acid base balance Flashcards
What is alkalaemia?
Plasma pH greater than 7.45
—> This leads to paraesthesia and tetany.
What is acidaemia?
Plasma pH less than 7.35
What happens in alkalaemia do?
- Alkalaemia lowers free calcium by causing Ca2+ ions to come out of solution.
- –> increases neuronal excitability.
What is the mortality rates of alkalaemia?
- 45% mortality if pH rises to 7.55
- 80% mortality at pH 7.65.
What happens in acidaemia?
- Acidaemia increases plasma potassium ion concentration.
- –> This effects excitability and can lead to arrhythmia.
- Increasing the concentration of H+ affects many enzymes, which can denature enzymes and effect muscle contractility, glycolysis and hepatic function.
- effects are severe below pH 7.1
- Life threatening below pH 7.0
What is pCo2 determined by?
- It is determined by respiration.
it is controlled by chemoreceptors. - It is disturbed by respiratory disease.
What is [HCO3-] determined by?
- determined by the kidneys.
- It is disturbed by metabolic and renal disease.
How do the kidneys work to control plasma pH?
- The kidneys control pH.
- –> There is variable recovery of hydrogen carbonate and active secretion of hydrogen ions.
How do the lungs work to control plasma pH?
- Alveolar ventilation allows diffusion of O2 into blood and CO2 out of blood.
- –> control pO2 and pCO2.
- The rate of ventilation is controlled by chemoreceptors.
What is the normal concentration of HCO3- in arterial blood?
The range is 22-26 mmol.I-1
Why does the acid we produce due to metabolism not deplete HCO3-?
This is because:
- The kidneys recover all filtered HCO3-.
- The Proximal tubule makes HCO3- from amino acids, putting NH4+ into urine.
- The distal tubule makes HCO3- from CO2 and H20.
- –> H+ is also buffered by phosphate and ammonia in the urine.
Describe the renal control of HCO3- (recovery).
- HCO3- is filtered at the glomerulus.
- It is mostly recovered in the PCT.
- H+ excretion is linked to Na+ entry in the PCT.
- H+ reacts with HCO3- in the lumen to form CO2 which enters the cell.
- It is converted back to HCO3- which enters ECF.
How is HCO3- created?
- Glutamine —> glutamate —> alpha ketoglutarate.
- –> It produces HCO3- and ammonium (NH4+)
- ———-> This then dissociates into ammonia and H+.
- –> HCO3- enters the ECF.
- –> NH4+ enters the lumen (urine)
What is the major adaptive response to an increased load in healthy individuals?
Excretion of ammonium is the major adaptive response.
How is ammonium generation from glutamine in proximal tubule be increased?
It can be increased in response to low pH.
How is NH4+ converted to H+?
NH4+ —> NH3 + H+
- NH3 freely moves into the lumen and throughout the interstitium.
- H+ is actively pumped into the lumen in the DCT and CT.
- H+ combines with NH3 to form NH4+ which is trapped in the lumen.
- NH4+ can also be taken up in the TAL and transported to interstitium and dissociates to H+ and NH3 —> goes to lumen of collecting ducts.
What is the minimum pH of urine?
4.5
What does acidosis?
Hyperkalaemia
- potassium ions move out of cells.
- Decreased potassium excretion in distal nephron.
What does alkalosis?
Hypokalaemia
- Potassium ions move into cells.
- Enhanced excretion of potassium in distal nephron.
What happens in hyperkalaemia?
- Hyperkalaemia makes intracellular pH of tubular cells more alkaline.
- –> H+ ions move out of the cells.
- –> This favours HCO3- excretion. —> Metabolic acidosis.
What happens in hypokalaemia?
- Hypokalaemia makes the intracellular pH of tubular cells more acidic.
- –> H+ ions move into the cells.
- –> This favours H+ excretion and HCO3- recovery. —> Metabolic alkalosis.
What is respiratory acidosis (acidaemia)?
- high pCO2
- normal HCO3-
- Low pH
What is respiratory acidosis (acidaemia) characterised by?
- high pCO2
- normal HCO3-
- Low pH
What is respiratory alkalosis (alkalaemia) characterised by?
- Low pCO2
- normal HCO3-
- Raised pH
What does hypoventilation lead to?
- hypoventilation leads to hypercapnia —> pCO2 rises
What does hyperventilation lead to?
- Hyperventilation leads to hypocapnia. —> pCo2 falls.
What compenates for changes in pCO2?
Compensated by changes in [HCO3].
How is respiratory acidosis compensated for?
- The kidneys would increase [HCO3]
- SO in the end there would be:
1. high pCO2
2. Raised [HCO3-]
3. Relatively normal pH.
How is respiratory alkalosis compensated for?
- The kidneys would decrease [HCO3-] to compensate for respiratory alkalosis.
- So in the end there would be:
1. Low pCO2
2. Lowered [HCO3-]
3. Relatively normal pH
What happens in metabolic acidosis?
- The tissues produce acid which reacts with and removes HCO3-.
- There is a fall in [HCO3-] leading to a fall in pH.
*The extra CO2 produced is breathed off at the lungs so there is no increase in arterial pCO2.
What is the anion gap?
This is the difference between measured cations and anions.
- ([Na+] + [K+]) - ([CL-]+[HCO3-]
- –> It is normally 10-18 mmol.I -1
When are there changes in the anion gap?
- The gap is increased if HCO3- is replaced by other anions.
- –> If a metabolic acid such as lactic acid reacts with HCO3-, the anion of the acid replaces HCO3-.
Where are there no changes in the in the anion gap?
- In renal causes of acidosis the anion gap is unchanged because:
1. not making enough HCO3- but this is replaced by Cl-.
What is metabolic acidosis characterised by?
- Normal pCO2
- Low HCO3-
- Low pH.
What is compensated metabolic acidosis characterised by?
- Low HCO3-
- Lowered pCO2
- Nearer normal pH
What is pH drop detected by and what does it lead to?
- Peripheral chemoreceptor ( carotid bodies) detect pH drop.
1. They stimulate ventilation
2. Leads to decrease pCO2.
When does metabolic alkalosis occur?
It occurs if [HCO3-] increases.
What is metabolic alkalosis characterised by?
- Normal pCO2
- Raised HCO3-
- Increased pH
What can not compensate metabolic alkalosis?
- It cannot be compensated to a great extent by reducing breathing as need to maintain pO2.
What conditions lead to respiratory acidosis?
- Type 2 respiratory failure
- Low pO2 and high pCO2
- The alveoli cannot be properly ventilated.
- These include severe COPD, severe asthma, drug overdose and neuromuscular disease.
What conditions lead to respiratory alkalosis?
- Hyperventilation
- Anxiety/ panic attacks - acute setting.
- Low pCO2 leads to a 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 conditions lead to metabolic acidosis is the anion gap is increased?
- kets-acidosis
- –> diabetes - Lactic acidosis
- –> Exercising to exhaustion
- –> poor tissue perfusion - Uraemic acidosis
- –> Advanced renal failure
- ———-> reduced acid secretion leads to build up of phosphate, sulphate and urate in blood.
What does increased anion gap indicate?
- Increased anion gap indicates a metabolic production of an acid.
What conditions lead to metabolic acidosis with a normal anion gap?
- Renal tubular acidosis
- This has 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- reabsorption. - Severe persistent diarrhoea can also lead to metabolic acidosis due to loss of HCO3-.
- –> HCO3- is replaced by CL- therefore the anion gap is unaltered.
What indicates that the anion gap is normal?
- If anion gap is normal HCO3- is replaced by Cl-.
What do non-renal causes of metabolic acidosis cause?
- They cause increased reabsorption of K+ by kidneys and movement of K+ out of cells.
- –> This leads to hyperkalaemia.
- 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+ is lost in urine.
What conditions lead to metabolic alkalosis?
- HCO3- is retained in place of Cl-.
- The stomach is a major site of HCO3- production.
- –> By-product of H+ secretion.
- –> Severe prolonged vomiting leads to loss of H+.
- –> Or mechanical drainage of stomach. - Potassium depletion/ mineralocorticoid excess.
- Certain diuretics (loop and thiazide)
What is metabolic alkalosis corrected by?
- Rise in pH of tubular cells which leads to fall in H+ secretion and reduction in HCO3- recovery.
- But there is a problem if there is also volume depletion because:
- –> The capacity to loose HCO3- is reduced because of the high rate of Na+ recovery.
- –> Recovering Na+ favours H+ excretion and HCO3- recovery.
How does metabolic alkalosis lead to hypokalaemia?
- Less H+ is excreted in the nephron which leads to more K+ being excreted.
- Alkalosis also causes movement of K+ ions into cells.
How do the values indicate Respiratory acidosis/ alkalosis?
If pCO2 is not normal, [HCO3-] is normal and pH has changed in opposite direction to pCO2.
How do the values indicate Metabolic acidosis/ alkalosis?
If [HCO3-] is not normal, pCO2 is normal and pH has changed In the same direction as [HCO3-]
How do the values indicate compensated respiratory acidosis?
- note that metabolic alkalosis can not be compensated for*
If pCO2 is high, [HCO3-] is raised and pH is relatively normal.
How do the values indicate compensated respiratory alkalosis or compensated metabolic acidosis?
If [HCO3-] is low, pCO2 is low, pH is relatively normal.
