Potassium and more L16 Flashcards
what is the normal intracellular concentration of K+?
140mM
what is the normal extracellular concentration of K+?
4mM
At what point is the cellular equilibrium of K+ reached? What is this value normally? (think back to Nernst equation)
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)
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?
- 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
what are the causes of hyperkalaemia?
- 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
How do K+ sparing diuretics work?
work to decrease water reabsorption without increasing K+ secretion.
two mechanisms:
- competitive antagonists with aldosterone for intracellular cytoplasmic receptor sites
- 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
Why does insulin deficiency cause hyperkalaemia?
- insulin increases rate of k+/Na+ ATPase
- allows more K+ to enter cells
- therefore insulin deficiency leads to more K+ in extracellular space > hyperkalaemia
What are treatments for hyperkalaemia?
-treat the cause
-K+ restricted diet
-insulin + glucose(to stimulate insulin release)
-
What are causes of hypokalaemia?
- diarrhoea
- furosemide
- insulin overdose
What are treatments for hypokalaemia?
- give K+ (IV if acute, oral if chronic)
- treat the cause
- aldosterone antagonists (K+ sparing diuretics - spironolactone)
What are the functions of aldosterone?
- volume regulation - RAAS
- main hormone for regulating K+ concentration in the body
Describe Ca2+ filtration through the nephron.
- 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)
Describe sulfate reabsorption in the nephron.
- 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
what happens when there is an absence of the NaS1 transporter?
-high sulphate in urine (hypersulfaturia) /low plasma sulfate (hyposulfatemia)
is sulphate reabsorption Tm limited?
yes
what happens to red cell production at high altitudes?
increases
Where is EPO synthesised in the kidney?
mesangial cells
What is the stimulus for EPO production and release?
hypoxia (mediated by the release of prostaglandins)
How does low iron lead to EPO production?
- 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.
How does EPO stimulate red cell production?
- EPO binds to EPOR (erythropoietin receptor) in bone marrow
- increases production of proerythroblasts
- these then become erythrocytes
EPO production falls in most causes of renal failure leading to anaemia. What is one exception?
polycystic kidney disease - sufficient renal tissue is present to produce EPO (tissue is there, just disorganised)
What is the treatment of anaemia in renal failure?
EPO analogues
Give an example of an EPO analogue.
Darbepoeitin alfa
What is the danger of abusing EPO analogues?
- increased risk of thrombosis
- high increase in haematocrit leading to increased viscosity and decreased flow
- proteinuria
