Potassium and more L16 Flashcards

1
Q

what is the normal intracellular concentration of K+?

A

140mM

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2
Q

what is the normal extracellular concentration of K+?

A

4mM

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3
Q

At what point is the cellular equilibrium of K+ reached? What is this value normally? (think back to Nernst equation)

A

will be reached when

([K+]intracellularly) / ([K+]extracellularly) is constant i.e. reaches a value and remains at that value.

Normally this ratio would be 140/4 (=35)

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4
Q

If more K+ ions are added to the extracellular space, some will move into the intracellular space and a new equilibrium will form. How would we calculate what this new equilibrium would be and how many K+ ions have moved intracellularly?

A
  • denote the amount of K+ ions moving intracellularly as x mmol
  • figure out the new intracellular and extracellular K+ concentrations in terms of x
  • the new equilibrium will be formed when the ratio of K+ concentrations is the same as the start/normal value
  • therefore it should equal 140/4
  • form the equation and solve to find x telling you how many K+ ions have moved and thus the new equilibrium

*if still don’t understand look at first page of lecture handout

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5
Q

what are the causes of hyperkalaemia?

A
  • end stage renal failure
  • crush injuries
  • blood transfusion (rbcs leak K+ after long time in storage)
  • cytotoxic drugs
  • insulin deficiency
  • overuse of K+ sparing diuretics
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6
Q

How do K+ sparing diuretics work?

A

work to decrease water reabsorption without increasing K+ secretion.

two mechanisms:

  1. competitive antagonists with aldosterone for intracellular cytoplasmic receptor sites
  2. directly block sodium (ENaC) channels

for 1, preventing aldosterone reaction from occurring so Na+/K+ exchange in collecting tubule does not occur so Na+ not reabsorbed and K+ not secreted

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7
Q

Why does insulin deficiency cause hyperkalaemia?

A
  • insulin increases rate of k+/Na+ ATPase
  • allows more K+ to enter cells
  • therefore insulin deficiency leads to more K+ in extracellular space > hyperkalaemia
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8
Q

What are treatments for hyperkalaemia?

A

-treat the cause
-K+ restricted diet
-insulin + glucose(to stimulate insulin release)
-

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9
Q

What are causes of hypokalaemia?

A
  • diarrhoea
  • furosemide
  • insulin overdose
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10
Q

What are treatments for hypokalaemia?

A
  • give K+ (IV if acute, oral if chronic)
  • treat the cause
  • aldosterone antagonists (K+ sparing diuretics - spironolactone)
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11
Q

What are the functions of aldosterone?

A
  • volume regulation - RAAS

- main hormone for regulating K+ concentration in the body

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12
Q

Describe Ca2+ filtration through the nephron.

A
  • PT: moves transcellularly into interstitial space (channels on apical, active on basolateral). Ca2+ movement proportions to water movement
  • TAL: paracellular reabsorption into tubule driven by positive potential in lumen of TAL (due to Na+/K+ transporter and K+ recycling)
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13
Q

Describe sulfate reabsorption in the nephron.

A
  • mainly reabsorbed in PT
  • uses Na+ gradient/ Na-dependent apical cotransporter
  • apical co-transporter = NaS1 - tranports 3Na+ with 1 sulphate ion
  • basolateral surface has anion exchangers that transport sulphate into interstitium
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14
Q

what happens when there is an absence of the NaS1 transporter?

A

-high sulphate in urine (hypersulfaturia) /low plasma sulfate (hyposulfatemia)

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15
Q

is sulphate reabsorption Tm limited?

A

yes

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16
Q

what happens to red cell production at high altitudes?

A

increases

17
Q

Where is EPO synthesised in the kidney?

A

mesangial cells

18
Q

What is the stimulus for EPO production and release?

A

hypoxia (mediated by the release of prostaglandins)

19
Q

How does low iron lead to EPO production?

A
  • transcription of EPO is stimulated by hypoxia-inducible factor (HIF), particularly HIF-2 = transcription factor
  • Fe2+ is a cofactor in HIF-alpha deoxygenase
  • HIF-alpha deoxygenase is involved in HIF-alpha degradation
  • less HIF –> less EPO
  • therefore low iron leads to increased EPO production as more transcription factor.
20
Q

How does EPO stimulate red cell production?

A
  • EPO binds to EPOR (erythropoietin receptor) in bone marrow
  • increases production of proerythroblasts
  • these then become erythrocytes
21
Q

EPO production falls in most causes of renal failure leading to anaemia. What is one exception?

A

polycystic kidney disease - sufficient renal tissue is present to produce EPO (tissue is there, just disorganised)

22
Q

What is the treatment of anaemia in renal failure?

A

EPO analogues

23
Q

Give an example of an EPO analogue.

A

Darbepoeitin alfa

24
Q

What is the danger of abusing EPO analogues?

A
  • increased risk of thrombosis
  • high increase in haematocrit leading to increased viscosity and decreased flow
  • proteinuria