Week 6 - Renal Control of Acid and Base Flashcards
What is the normal range of pH?
7.35-7.45
What is alkalaemia and what are its clinical effects?
When plasma pH is greater than 7.45
- Reduces the solubility of calcium salts
- – Free Ca2+ leaves the ECF, binding to bone and proteins
- – Hypocalcaemia results
- – Makes nerves much more excitable, producing paraesthesia and eventually uncontrolled muscle contractions (tetany)
- If pH > 7.55, 45% of patients die
- If pH > 7.65, 80% of patients die
What is acidaemia and what are its clinical effects?
When plasma pH is lower than 7.35
- Increases plasma potassium ion concentration
- – Effects excitability (particularly of cardiac muscle)
- – Arrhythmia
- – Increasing [H+] denatures proteins
- – Disturbs enzymes
- – Affects muscle contractility, glycolysis, hepatic function
- Effects are severe pH
Describe the carbon dioxide/hydrogen carbonate buffer system
- The [H+] in ECF is so low, the addition of very small amounts of acid would change the concentration and hence pH dramatically
- This doesn’t happen because H+ ions are buffered by binding to various sites
- Most important buffer = CO2/HCO3 system
- – CO2 + H2O ←→ H+ + HCO3
- The extent to which the reversible reaction proceeds is determined by the ratio of [dissolved CO2] (determined by plasma pCO2 to [HCO3] (produced by erythrocytes)
What is respiratory acidaemia?
- Decreased pH, increased pCO2, no change HCO3, decreased pO2
- Hypoventilation leads to hypercapnia so the ratio is altered and pH will fall
- Compensated by the kidneys:
- – Rise in pCO2 so [HCO3-] rises proportionately to restore pH
What is respiratory alkalaemia?
- Increased pH, decreased pCO2, no change HCO3, increased/same pO2
- Hyperventilation leads to hypocapnia, so the ratio is altered and pH will rise
- Compensated by the kidneys:
- – Fall in pCO2 so [HCO3-] falls proportionately to restore pH
What is metabolic acidosis?
- Decreased pH, same pCO2, decreased HCO3, same pO2, increased anion gap
- Metabolically produced H+ ions react with HCO3- to produce CO2 in venous blood
- – This CO2 is breathed out through the lungs, giving a directly proportional reduction in arterial HCO3-
- – Relatively less H+ ions are buffered so pH decreases
- Compensated by the lungs
- – Fall in [HCO3] causes increased ventilation so pCO2 is lowered proportionately
What is metabolic alkalosis?
- Increased pH, same pCO2, increased HCO3, decreased/same pO2
- If plasma [HCO3-} rises, for example after persistent vomiting, the [HCO3-] : pCO2 ratio will be altered
- More HCO3 than CO2 so relatively more H+ ions are buffered causing a pH increase
- – Rise in [HCO3] causes decreased ventilation so pCO2 is raised proportionately
Describe the cellular mechanisms of reabsorption of HCO3- in the proximal tubule
- 3Na-2K-ATPase sets up a [Na+] gradient in PCT cells
- H+ ions are pumped out of the apical membrane up their concentration gradient in exchange for Na+
- The H+ reacts with filtered HCO3 producing CO2, which enters the cell and reacts with water to produce H+
- The H+ is quickly exported, recreating HCO3- which crosses the basolateral membrane to enter the plasma
80-90% of HCO3 is reabsorbed in the PCT
- Up to 15% is reabsorbed in the TAL of the loop of Henle by a similar method
Describe the cellular mechanisms of H+ excretion in the distal tubule
- By the DCT most/all of the filtered HCO3 has been recovered
- The Na+ gradient is also insufficient to drive H+ secretion
- H+ is pumped across the apical membrane by H+-ATPase
- When cells export H+, K+ is absorbed into the blood
- – So by exporting a lot of H+, a lot of K+ will also be absorbed
Describe the mechanism of buffering of H+ in urine
- The minimum pH of urine is 4.5
- There is no HCO3 as it has all been recovered
- Some H+ has been buffered by phosphate (titratable)
- – Titratable means that it can freely gain H+ in an acid/base reaction
- Some has reacted with ammonia to form ammonium
Describe the effect of metabolic acidosis on plasma [K+]
Associated with hyperkalaemia
- Acidosis causes K+ ions to move out of cells
- There is more K+ reabsorption in the distal nephron
- As [K+] rises, the kidney’s ability to reabsorb and create HCO3 is reduced
- Hyperkalaemia makes intracellular pH alkaline, favouring HCO3 excretion
Describe the effect of metabolic alkalosis on plasma [K+]
Associated with hypokalaemia
- K+ ions move into cells
- Less K+ reabsorption in the nephron
- Hypokalaemia makes intracellular pH acidic, favouring H+ excretion and HCO3 recovery
What is the effect of vomiting on acid-base status?
[HCO3] can increase after persistent vomiting, causing metabolic alkalosis
- HCO3 can be rapidly excreted following infusion of HCO3 so is easy to correct
- Rise in pH of the tubular cells leads to a fall in H+ excretion and a reduction in HCO3 recovery
- – H+ excretion has stopped so K+ reabsorption has also stopped
- – Can cause hypokalaemia
- Problem if there is volume depletion:
- – Capacity to lose HCO3 is reduced because of high rate of Na+ recovery
- – Recovering Na+ favours H+ excretion and HCO3 recovery
- – If you correct the dehydration by giving fluids, HCO3 will be excreted very rapidly
What can cause metabolic acidosis?
- Excess metabolic production of acids (e.g. lactic acidosis, ketoacidosis)
- Acids are ingested
- HCO3 is lost
- A problem with renal excretion of acid
What is the anion gap?
Difference between [Na+] + [K+] and [Cl-] + [HCO3]
- This gap increases if other anions from metabolic acids replace HCO3
- If HCO3 is replaced in the plasma by another anion, the gap will increase
Why is it important to maintain ECF [K+]?
- It has an effect on the resting membrane potential
- – The high ICF [K+] and low ECF [K+] creates a gradient for K+ to move out of the cell, resulting in the resting membrane potential
- – Decreased ECF [K+] increases the gradient and hyperpolarises the cell
- – Increased ECF [K+] decreases the gradient and depolarises the cell
- Can affect the excitability of cardiac tissue
- High [K+] inside cells and inside mitochondria is essential for:
- – Maintaining cell volume
- – Regulating pH
- – Controlling cell enzyme function
- – DNA and protein synthesis
- Low ECF [K+] can cause metabolic disturbances:
- – Inability of the kidney to form concentrated urine
- – A tendency to develop metabolic alkalosis
- – Enhancement of renal ammonium excretion
Where is K+ secreted and how?
Distal tubule and cortical collecting duct (principal cells)
- Na-K-ATPase activity in the basolateral membrane creates a K+ gradient (high intracellular K+) for secretion
- Na+ moves from the lumen into the cell down its concentration gradient, creating an electrical gradient
- Together these create a favourable electrochemical gradient for K+ secretion via apical K+ channels
Where is K+ reabsorbed?
- Proximal tubule
- Thick ascending limb
- Distal tubule/cortical collecting duct (intercalated cells)
- – Active process
- – Mediated by H-K-ATPase in apical membrane
- Medullary collecting duct (intercalated cells)
What factors affect K+ secretion?
- ECF [K+]
- Aldosterone
- Acid base status
- – Acidosis decreases K+ secretion
- – Alkalosis increases K+ secretion
- Increased distal tubular flow rate
- – Washes away luminal flow
- – Increases K+ loss
- Increased Na delivery to distal tubule
- – More Na absorbed, so more K+ is lost
What is external potassium balance?
- Adjusts K+ excretion to correct imbalance
- Much slower to act
- 6-12 hours to excrete a load of K+
- Responsible for control of total body potassium content over the longer term
- The kidneys adjust K+ excretion to match intake by controlling K+ secretion
What is internal potassium balance?
- Moves K+ between ICF and ECF
- Effect is immediate
- Responsible for moment-moment control
- Movement of K+ from ECF into cells is mediated by Na-K-ATPase
- Movement of K+ out of cells into ECF is via K+ channels (ROMK)
What stimulates movement of K+ from ECF into cells is mediated by Na-K-ATPase?
- Hormones (insulin, aldosterone, catecholamines)
- – K+ in splanchnic blood stimulates insulin secretion by pancreas, which stimulates Na-K-ATPase
- – Aldosterone secretion is stimulated by K+ in the blood, which then stimulates Na-K-ATPase
- – Catecholamines act via β2- adrenoceptors, which stimulate Na-K-ATPase
- Increased [K+] in ECF
- Alkalosis – low ECF [H+]
What stimulates movement of K+ out of cells into ECF?
It is via K+ channels (ROMK)
- Exercise
— Net release of K+ during recovery phase of action potential
— Skeletal muscle damage releases K+, but there is uptake of K+ by non-contracting tissues
— Also increase catacholamines, which offset ECF [K+] rise
- Cell lysis
— Trauma to skeletal muscle causing muscle cell necrosis
— Intravascular haemolysis
— Cancer chemotherapy – tumour cell lysis
- Increase in ECF osmolarity
— Can be caused by diabetic ketoacidosis
— Increased plasma and ECF tonicity makes water move into ECF
— This increases [K+] in ICF and hence K+ leaves down concentration gradient
- Low ECF [K+]
- Acidosis - increase in ECF [H+]
— Acidosis leads to a shift of H+ into cells and hence a reciprocal shift of K+ out of cells
• Acidosis leads to hyperkalaemia
— Alkalosis leads to a shift of H+ out of cells and a reciprocal shift of K+ into cells
• Alkalosis leads to hypokalaemia
Describe common causes of hypokalaemia
- May be due to problems of external balance
— Excessive loss
• GI – diarrhoea/bulimia/vomiting
• Renal loss of potassium (diuretic drugs, osmotic diuresis, high aldosterone levels) - May be due to problems of internal balance
— Shifts of potassium into ICF
• E.g. metabolic alkalosis
How does hypokalaemia affect acid-base status?
- There is a shift of K+ out of cells and hence a reciprocal H+ shift into the cells
- Causes alkalosis
What are the clinical features of hypokalaemia?
- Heart: altered excitability - arrhytmias
- GI: neuromuscular dysfunction – paralytic ileus
- Skeletal muscle: neuromuscular dysfunction – muscle weakness
- Renal: unresponsive to ADH – nephrogenic DI
How can you treat hypokalaemia?
- Treat cause
- Potassium replacement – IV/oral
- If due to increased mineralocorticoid activity, give K+ sparing diuretics which block action of aldosterone on principal cells
How does hyperkalaemia affect acid-base status?
- There is a shift of K+ into cells and hence a reciprocal shift of H+ out of cells
- Causes acidosis
What are some causes of hyperkalaemia?
- May be due to problems of external balance
- Increased intake of K+
— Only causes hyperkalaemia if renal dysfunction occurs
• If there is decreased renal excretion
• Acute or chronic kidney injury
• Normal kidneys but drugs which block potassium excretion (e.g. ACEI)
• Low aldosterone state
— Unless an inappropriate dose is given IV - May be due to internal shifts
— Diabetic ketoacidosis
— Cell lysis
— Metabolic acidosis
— (Exercise)
What are the clinical features of hyperkalaemia?
- Heart = altered excitability
- – Arrhythmias, heart block
- GI = neuromuscular dysfunction
- – Paralytic ileus
- Acidosis
How can you treat hyperkalaemia in an emergency?
- Reduce K+ effect on heart
- – IV calcium gluconate
- Shift K+ into ICF by:
- – Glucose + insulin IV
- – Nebulised beta agonists
- Remove excess K+
- – Dialysis
How can you treat hypokalaemia in an emergency?
- Treat cause
- – Stop medications
- – Treat diabetic ketoacidosis
- Reduce intake
- Measures to remove excess K+
- – Dialysis
- – Oral K+ binding resins to bind K+ in gut
