Potassium and more

Question 1

What is the conc of K+ in the intracellular and extracellular space?
What is the signicicance of this?

Answer 1

Extracellular = 4mM
Intracellular = 140mM
If K+ is added to extracellular space, it will eventually re-equilibrate with intracellular K+. However this takes time to develop so for acute loads K+ remains in the extracellular space

Question 2

What are the causes, consequences and treatments of hyperkalaemia?

Answer 2

Causes:
- end-stage renal failure, crush injuries, blood transfusion, cytotoxic drugs, insulin deficiency, over-use of K+ sparing diuretics
Consequences:
- dysrhythmias
Treatments; treat the cause, K+ restricted diet (if chronic), insulin and glucose (increases rate of Na+K+ATPase

Question 3

What are the sites of renal K+ exchange?

Answer 3

proximal tubules: reabsorption passively and paracellularly with water
thick ascending limb: through the NKCC cotransporter, but much of the K+ cycles back into the filtrate here
Distal tubule through to collecting ducts
- apical membrane K+ channel (ROMK), under control of aldosterone
- a Ca2+ activated K+ channel (flow rate dependent)

Question 4

How are diuretics and K+ related?

Answer 4

Most diuretics increases distal K+ secretions, by both increasing distal Na+ delivery and by increasing amount of water in the filtrate (dropping the K+ concentration)
e.g. furosemide –> hypokalaemia

Question 5

Why is aldosterone important?

Answer 5

Important in volume regulation (as part of RAAS), but its secretion is also very sensitive to K+
It is the main hormone regulating K+ concentration in the body
An increase in K+ conc will lead to aldosterone release

Question 6

What is the fate of filtered calcium?

Answer 6

20% of plasma free Ca2+ is filtered
Proximal tubule: moves transcellularly (channels on apical, active on basolateral), proportional to water movement
Thick ascending limb: absorption, driven by the positive potential in the lumen of TAL driving the above mechanism

Question 7

Describe sulphate reabsorption in the proximal tubule

Answer 7

Na+ dependent apical co-tranporter
NaS1
sulphate movement is T limited

Question 8

What kind of hormone is EPO?
Where is it synthesised?
What is its production and release stimulated by?

Answer 8

• glycoprotein hormone
  -synthesised from peritubular fibroblasts (mesangial cells) in the renal cortex
• stimulated by hypoxia, mediated by the release of prostaglandins
  hypoxia-inducible factors
  HIF-alpha degradation enhanced by Fe2+

Question 9

What are the actions of EPO?

Answer 9

• anti-apoptotic agent for erythrocytic progenitors
• in the bone marrow, EPO binds to EPOR which increases the production of erythroblasts, when then become erythrocytes
• EPOR activates JAK2 (Janus Kinase) tyrosine kinase which then activates different intracellular pathways including: Ras/MAP kinsas, PhINS 3 kinase and STAT transcritption factors
• The EPOR receptors clears the EPO by biding and internalisation so low EPOR expressive leads to a higher EPO concentration and linger half-life

Question 10

Describe EPO in renal failure

What cause of renal failure preserves EPO

Answer 10

• EPO production falls in most causes of renal failure leading to anaemia
• one expection is renal failure associated with polycystic kidney disease, in sufficient renal parenchyma is present to prevent the loss of EPO production
• ## treament is to give EPO analogues

Question 11

Describe Vit D metabolism is the kindeys

Answer 11

Vit D from the diet/skin is converted to 25-hydroxycholecalciferol in the liver, then to 1,25-dihydroxycholecalciferol in the kidney
Under control of PTH and calcitonin
VitD increases Ca2+ and phosphate absorption from gut and decrease excretion