Potassium Regulation Flashcards

1
Q

Give the Nernst Equation.

A

E = (-RT/F) * log ([K+in] / [K+out])

Where:

F = Faraday
R = Gas constant
E = Equilibrium potential
T = Temperature (kelvin)
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2
Q

What is the ratio of [K+in] / [K+out] in a normal cell?

A

140/4 = 35

*Intracellular / extracellular

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3
Q

What can be said about the movement of potassium ions across a membrane if [K+in] / [K+out] is constant?

A

Equilibrium potential has been reached.

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4
Q

Why, for acute loads, does K+ tend to accumulate in the extracellular space?

A

Because the equilibrium, which is greater intracellularly, takes time to develop.

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5
Q

List 6 causes of hyperkalaemia.

A

1 - End-stage renal failure.

2 - Crush injuries.

3 - Blood transfusion.

4 - Cytotoxic drugs.

5 - Insulin deficiency.

6 - Over-use of K+ sparing drugs.

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6
Q

What is the consequence of hyperkalaemia?

A

Cardiac dysrhythmias.

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7
Q

List 3 causes of hypokalaemia.

A

1 - Diarrhoea.

2 - Furosemide.

3 - Insulin overdose.

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8
Q

What is the consequence of hypokalaemia?

A

Cardiac dysrhythmias.

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9
Q

List the sites of renal K+ exchange.

For each site, give the transporter responsible for the exchange.

A

1 - Proximal tubules (passively and paracellularly with water).

2 - Thick ascending limb (NKCC cotransporters).

3 - Distal tubule principal cells (apical K+ channels under the control of aldosterone and Ca2+ activated K+ channels which are dependent on flow).

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10
Q

Why is absorption of potassium at the thick ascending limb negligible?

A

Because most of the potassium cycles back into the filtrate there.

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11
Q

What is the main hormone regulating K+?

A

Aldosterone.

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12
Q

Why is only 10% of the total blood Ca2+ filtered at the glomerulus?

A

Because 20% of free plasma Ca2+ is filtered at the glomerulus, and half of Ca2+ is bound to albumin and other carriers.

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13
Q

Describe the process of sulfate reabsorption in the proximal tubule.

A

1 - 3Na+ and 1 SO4 2- enter via the apical membrane with the NaS1 cotransporter.

2 - SO4 2- exits the cell on the basolateral membrane via the sat1 antiporter, where it is exchanged in reverse for anions.

3 - The Na+ gradient is maintained by the basolateral 3Na+/2K+ pump.

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14
Q

Via which protein can SO4 2- exit the cell via the apical membrane?

In exchange for which molecule does SO4 2- exchange occur here?

A
  • The cfex antiporter.

- In exchange for anions.

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15
Q

What is the limiting factor for SO4 2- transport?

Give an example of another molecule that is limited in the same way.

A
  • SO4 2- is Tm limited (transport maximum).

- The same is true for glucose.

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16
Q

What type of molecule is the erythropoietin hormone?

A

A glycoprotein.

17
Q

How many amino acids comprise erythropoietin?

What is the mass in Da?

A
  • 166.

- 34kDa.

18
Q

What is the normal concentration of erythropoietin in the blood?

19
Q

Which cells synthesise erythropoietin?

A

Peritubular fibroblasts, sometimes called mesangial cells, in the renal cortex.

20
Q

What stimulates erythropoietin production and release?

21
Q

What are hypoxia-inducible factors?

What is the primary hypoxia-inducible factor?

A
  • Transcription factors which control the production and release of erythropoietin.
  • The primary hypoxia-inducible factor is HIF-2.
22
Q

Why does low blood Fe2+ lead to an increase in erythropoietin production?

A
  • HIF-alpha is a precursor to hypoxia-inducible factors.
  • Fe2+ is a cofactor in HIF-alpha dioxygenase, which catalyses the breakdown of HIF-alpha.
  • Hence, low blood Fe2+ leads to an increase in hypoxia-inducible factors and therefore an increase in erythropoietin production.
23
Q

List 3 factors, other than Fe2+, that control erythropoietin production.

A

1 - Prostaglandins.

2 - Beta-adrenoceptors.

3 - Angiotensin II.

24
Q

List 2 actions of erythropoietin.

A

1 - Acts as an anti-apoptotic agent for erythrocytic progenitors.

2 - Erythropoietin binds to erythropoietin receptors in the bone marrow to increase the production of proerythroblasts.

25
Describe the process of erythropoietin clearance.
- Erythropoietin binds to the EPOR receptor. - This activates the JAK2 tyrosine kinase. - This activates intracellular pathways including Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. - The EPOR receptor clears the erythropoietin by binding and internalisation.
26
Why might erythropoietin concentration be longer in some individuals?
Due to a low EPOR receptor expression or dysfunctional EPOR receptor.
27
Why might renal failure cause anaemia?
Due to a decrease in erythropoietin production.
28
In which form of renal failure will anaemia not occur?
Renal failure associated with polycystic kidney disease, in which sufficient renal parenchyma is present to prevent the loss of erythropoietin production.
29
How is anaemia of renal failure treated?
By giving synthetic erythropoietin analogues.
30
What type of anaemia occurs with anaemia of renal failure?
Normochromic normocytic anaemia.
31
Give an example of a synthetic erythropoietin analogue.
Darbepoetin alfa.
32
List 2 risks of erythropoietin abuse (e.g. for sport).
1 - Increased risk of thrombosis. 2 - Increased blood viscosity, which in turn decreases flow.
33
Can erythropoietin be found in the urine?
Normally in small amounts, but it is particularly abundant with abuse.
34
List the stages of processing of vitamin D. For each stage, state the location in the body where that stage occurs.
1 - Vitamin D from the diet or skin is converted into 25-hydroxyvitamin D in the liver. 2 - 25-hydroxyvitamin D is converted into 1,25-dihydroxyvitamin D in the kidney.
35
List 2 hormones that regulate the production of 1,25-dihydroxyvitamin D. What are their roles in vitamin D regulation?
1 - Parathyroid hormone (stimulates). 2 - Calcitonin (inhibits).
36
List the actions of 1,25-hydroxyvitamin D.
1 - To increase Ca2+ and phosphate absorption from the small intestine. 2 - To decrease Ca2+ and phosphate excretion.
37
Why might patients with renal failure have low 25-hydroxyvitamin D? What about 1,25-dihydroxyvitamin D?
- Low 25-hydroxyvitamin D might be due to dietary restrictions. - Low 1,25-dihydroxyvitamin D ia due to the failure of the kidney to convert 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D.
38
Which enzyme is responsible for the conversion of 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D?
1-alpha hydroxylase.
39
What is the cutoff molecular mass for glomerular filtration?
70kDa.