Session 5 Flashcards

1
Q

Describe the normal distribution of potassium across the fluid compartments.

A

98% in ICF, mainly within skeletal muscle but also in liver RBCs and bone; 2% in ECF.

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2
Q

Describe the internal balance of potassium regulation.

A

Potassium moves between the ECF and ICF via Na-K-ATPase and K channel action. Provides short term control.

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3
Q

How is potassium uptake into cells increased?

A

Via the action of insulin, aldosterone and catechoamines; due to increased potassium levels in the ECF or due to alkalosis.

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4
Q

What promotes potassium removal from cells?

A

Exercise, cell lysis, increased ECF osmolality, Low ECF potassium levels, acidosis.

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5
Q

Describe the external balance of potassium control.

A

Adjustment of renal potassium secretion to provide long term control of potassium levels.

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6
Q

How does insulin affect potassium levels?

A

Potassium in splanchnic blood stimulates potassium secretion by the pancreas; insulin causes increased Na-K-ATPase activity; more potassium is taken into muscle cells and the liver.

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7
Q

How does aldosterone affect potassium?

A

Potassium in the blood stimulates aldosterone release; aldosterone stimulates Na-K-ATPase so more potassium is taken up by cells.

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8
Q

How do catechoamines affect potassium?

A

Act on beta-2 adrenoceptors to stimulate Na-K-ATPase; causes increased potassium uptake by cells.

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9
Q

How does exercise affect potassium levels?

A

Potassium is released during the recovery phase of an action potential; skeletal muscle damage during exercise releases potassium; exercise causes catechoamine release. All factors cause increased potassium levels which are buffered by uptake of potassium by non-contracting cells.

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10
Q

What effect does acidosis have on potassium levels?

A

Causes hydrogen to move into cells; potassium moves out of cells in a reciprocal movement; results in hyperkalaemia.

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11
Q

How does alkalosis affect potassium levels?

A

Hydrogen moves out of cells; potassium moves into cells in a reciprocal movement; causes hypokalaemia.

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12
Q

What affect does hyperkalaemia have on blood pH?

A

More potassium moves into cells; hydrogen moves out of cells in reciprocal action; acidosis results as blood pH drops.

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13
Q

What effect does hypokalaemia have on blood pH?

A

More potassium leaves cells; hydrogen moves into cells in reciprocal action; alkalosis results as blood pH rises.

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14
Q

Where is most potassium normally absorbed in the kidneys?

A

Proximal tubule.

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15
Q

How is potassium resorbed in the proximal tubule?

A

Passively by paracellular diffusion.

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16
Q

How is potassium resorbed in the thick ascending limb of the kidney?

A

Actively using Na-K-ATPase in the basolateral membrane and Na-K-2Cl transporters in the apical membrane.

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17
Q

Where in the kidney can potassium resorption not be controlled (i.e. it is fixed)?

A

PT, TAL, intercalated cells of DCT, CCD and MCD.

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18
Q

Where in the kidney is potassium resorption variable (i.e. it can be regulated)?

A

Principal cells of the DCT and CCD.

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19
Q

How is potassium secreted in the principal cells of the DT and CCD?

A

Na-K-ATPase moves K from ECF into tubular cells; high intracellular K levels create gradient for secretion; apical ENaC moves sodium to create an electrical gradient for K secretion; K is secreted via apical K channels.

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20
Q

How is potassium secretion increased in the DT and CCD?

A
  • Increased ECF K levels stimulate Na-K-ATPase and increase apical K channel permeability so more potassium can be excreted.
  • Stimulates aldosterone release which increases transcription of Na-K-ATPase, K channels and ENaC so potassium secretion increases.
  • Alkalosis increases K secretion.
  • Increased tubular flow rate increases secretion as greater gradient.
  • Increased Na delivery in DT increases excretion as more Na is absorbed so greater gradient.
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21
Q

How is potassium resorbed in the DT and CCD?

A

By intercalated cells: active process mediated by apical H-K-ATPase.

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22
Q

What is hyperkalaemia?

A

Potassium raised above 5.0 mmol/L.

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23
Q

How may altered renal excretion cause hyperkalaemia?

A

AKI/chronic kidney injury prevents the kidney from secreting potassium effectively; drugs may block potassium excretion (ACE-inhibitors and potassium sparing diuretics); low aldosterone state reduces potassium secretion (due to Addison’s disease or ACEI).

24
Q

How can DKA affect potassium levels?

A

Causes hyperkalaemia: lack of insulin so less potassium excretion; metabolic acidosis increases ECF potassium; hyper-osmolarity in the ECF increases ECF potassium levels.

25
Q

How can cell lysis affect potassium levels?

A

Causes hyperkalaemia: cell lysis releases extra potassium into the ECF which can cause hyperkalaemia if in large amounts.

26
Q

In what situations may increased potassium intake cause hyperkalaemia?

A

If renal dysfunction is present or an inappropriate dose of IV potassium is given.

27
Q

How does hyperkalaemia present clinically?

A

Altered heart excitability (less excitable) causing heart block and arrhythmias; paralytic ileus in GI due to neuromuscular dysfunction; acidosis in blood.

28
Q

How is hyperkalaemia treated?

A

IV calcium gluconate immediately to reduce effect of potassium on the heart; then glucose and IV insulin and nebulised beta agonists (salbutamol) to shift potassium into ICF; may need to give dialysis as medium term solution; long term treatment is to treat underlying cause and remove excess potassium by dialysis or oral K binding resins.

29
Q

How may problems in the external balance of potassium lead to hypokalaemia?

A

Excessive loss of K via diarrhoea, bulimia or vomiting in GI; renal loss from diuretics, osmotic diuresis or high aldosterone.

30
Q

How may problems in the internal balance of potassium cause hypokalaemia?

A

Potassium shifts into the ECF, e.g. Due to metabolic acidosis.

31
Q

How does hypokalaemia present clinically?

A

Altered excitability of heart (more excitable) leading to arrhythmias; paralytic ileus due to GI NMJ problems; muscle weakness due to skeletal muscle NMJ problems; nephrogenic DI as kidneys become unresponsive to ADH.

32
Q

How is hypokalaemia treated?

A

Treat the underlying cause; may require IV or oral potassium replacement therapy too.

33
Q

What is the normal physiological range of pH in blood plasma?

A

7.35-7.45.

34
Q

How is blood pH controlled?

A

By tightly regulating plasma hydrogen ion concentration.

35
Q

Define acidaemia of the blood.

A

Blood plasma pH below 7.35.

36
Q

Define alkalaemia of the blood.

A

Blood plasma pH above 7.45.

37
Q

What effect does alkalaemia have on calcium and what are the clinical implications of this?

A

Forces calcium ions out of solution which increases neuronal excitability. Leads to parasthesia and tetany.

38
Q

What are the clinical implications of acidaemia?

A

Proteins are denatured so enzyme function decreases; can affect muscle contractility, glycolysis and hepatic function.

39
Q

How is blood plasma pH determined?

A

Using the Henderson-Hasselbach equation:
pH=pK + log ((HCO3-)/(pCO2*0.23))
pK=6.1 at body temperature.

40
Q

What effect does hypoventilation have on pCO2 and pH?

A

Increases pCO2 (hypercapnia), leading to a decrease in plasma pH and respiratory acidaemia.

41
Q

What effect does hypoventilation have on pCO2 and pH?

A

Decreases pCO2 (hypocapnia), leading to a rise in pH and respiratory alkalaemia.

42
Q

How is pCO2 controlled?

A

Using chemoreceptors:

  • Central chemoreceptors adjust ventilation rate to account for respiratory disturbances and act slowly but cause most of the change.
  • Peripheral chemoreceptors detect changes in pCO2 and pH and act rapidly but are responsible for little of the overall change.
43
Q

What causes metabolic acidosis?

A

Acids produced by tissues in metabolism reacts with bicarbonate producing CO2 and water; CO2 is blown off in the lungs and the decreased plasma [bicarb] decreases pH, causing metabolic acidosis.

44
Q

How is metabolic acidosis compensated?

A

Peripheral chemoreceptors increase ventilation to correct pH; kidneys make and conserve more bicarb from CO2 and water or amino acids.

45
Q

How and where in the kidney is bicarb conserved?

A

Mainly conserved in the PCT, Na gradient from Na-K-ATPase drives H into the tubular lumen via NHE-3, H reacts in lumen to form CO2 which enters tubular cells, reacts and produces bicarb which moves into the ECF via Na-3HCO3 cotransporters.

46
Q

How is bicarb produced in the PCT of the kidney?

A

Glutamine is converted to alpha-ketoglutarate to produce bicarb and ammonium.

47
Q

How is bicarb produced in the DCT of the kidney?

A

CO2 from metabolism reacts with water to form bicarb and hydrogen.

48
Q

What happens to hydrogen produced in the kidney as a by-product of bicarb production?

A

Secreted actively into the tubular lumen via H-ATPase, in urine it is buffered by excreted ammonia and phosphate ions to prevent a decrease in pH.

49
Q

What cellular responses result from acidosis?

A

Na/H exchanger activity is increased; ammonium production in the PCT increases; H-ATPase activity in the DCT increases.

50
Q

How is the anion gap calculated?

A

Difference between the concentrations of sodium and potassium ions and chloride and bicarb ions.

51
Q

What does an increased anion gap suggest?

A

Metabolic acidosis as an unmeasured metabolically produced anion has replaced bicarb.

52
Q

Is there always an anion gap in metabolic acidosis? Why?

A

No, some metabolically produced ions are accounted for in the anion gap (e.g. Chloride) so if one of these replaces bicarb there will be no increase in the anion gap, despite the presence of metabolic acidosis.

53
Q

How does repeated vomiting lead to metabolic alkalosis?

A

Vomiting causes stomach cells produce more H to replace lost acid; bicarb is produced in the same reaction and enters blood; increased blood plasma [bicarb] causes alkalosis.

54
Q

How can metabolic alkalosis be compensated for?

A

By increasing ventilation, only partial compensation as ability to increase ventilation is limited.

55
Q

How can low blood pressure impede on pH regulation?

A

If low blood pressure Na recovery from urine increases; recovery of sodium favours hydrogen excretion and bicarb recovery; if alkalosis is present then may lead to worsened alkalosis; maintenance of BP takes priority over pH regulation.