Potassium, calcium, sulphate and endocrine

Question 1

Where is the K reservoir?

Answer 1

Intracellular - 140mM

Question 2

When is cellular equilibrium reached for K?

Answer 2

When [K]inside / [K]outside is constant

Usually 140/4

Question 3

What ensures a resting membrane potential across the cell?

Answer 3

Na/K ATPase. Move 2K in to ensure that K concentration is conserved

Question 4

Where does K distribute if administered IV?

Answer 4

Adds to ECS, some moves into ICS to establish the equilibrium bu this takes time to occur so ACUTE levels will remain in ECS.

Question 5

What is the problem with a K build up in ECS?

Answer 5

If potassium builds up or there is a release from the intracellular reservoir without compensation it can be fatal. Causes arrhythmias.

Question 6

What may cause a release of intracellular K?

Answer 6

Muscle damage, crush injury or burn injury

Question 7

What are the causes of HYPERkalaemia?

Answer 7

Endstage renal failure, crush injuries, blood transfusion (RBC leak in storgae), cytotoxic drugs, insulin deficiency, overuse of K sparing diuretics.

Question 8

What results from hyperkalaemia?

Answer 8

Cardiac arrhythmias

Question 9

How is hyperkalaemia treated?

Answer 9

Treat the cause and restrict K in diet
Give insulin and glucose as this stimulates the uptake of K into cells by increasing the rate of Na/K ATPase due to insulin allowing glucose uptake for energy.

Question 10

What causes HYPOkalaemia?

Answer 10

Diarrhoea, furosemide, insulin overdose (too much K sequestered into cells)

Question 11

What results from hypokalaemia?

Answer 11

Cardiac arrhythmias

Question 12

How is hypokalaemia treated?

Answer 12

Treat the cause and give K.
IV for acute or oral for chronic
Can target RAAS

Question 13

What controls K movement in PT?

Answer 13

Reabsorbed passively across basolateral and moves paracellularly with water.
Main site for reabsorption

Question 14

What controls K movement in Thick Ascending limb?

Answer 14

Reabsorption through NKCC2 but most cycles back into the filtrate to prevent a net movement

Question 15

What controls K movement in DT to MCD?

Answer 15

SECRETION of K through apical channel ROMK. Under the control of ALDOSTERONE and is Ca activated.

Question 16

What effect do diuretics have on K?

Answer 16

Diuretics will increase K secretion by increasing distal Na delivery and water into the filtrate, causing a fall in K concentration of the interstitium

Question 17

How does aldosterone affect K?

Answer 17

Regulates K concentration.

High K = aldosterone release for ROMK secretions, Na conservation and water retention

Question 18

How is RAAS inhibited to prevent hypokalaemia?

Answer 18

ACEi
Sartans
ARBs
Stop aldosterone production in response to K

Question 19

How much calcium is filtered in the glomerulus

Answer 19

20% of plasma free Ca (10% of total Ca)

Question 20

How does calcium move in the renal system?

Answer 20

Reabsorbed in PT transcellularly through apical channels and active transport across the basal, in proportion to water.
Reabsorbed in TAL due to the +ve potential in the lumen created by NKCC and K recycling into filtrate, so Ca moves paracellularly following the electrical gradient. TAL is main area for reabsorption.

Question 21

What allows Ca movement through apical channels in PT?

Answer 21

Ca concentration in cells is low so a small permeability allows movement

Question 22

How does sulphate move in the renal system?

Answer 22

An anion of the filtrate that is reabsorbed in the PT using the Na gradient.
NaS1 cotransporter on the apical membrane, followed by anion exchange on the basal. Tm limited.

Question 23

What does the absence of NaS1 lead to?

Answer 23

Hyposulfatemia and hypersulfaturia

Question 24

What are the 3 endocrine functions of the kidney?

Answer 24

EPO
RAAS
Vit D

Question 25

Why is EPO equired?

Answer 25

For RBC production and increased haematocrit.

Question 26

Where is EPO synthesised and what stimulates it?

Answer 26

In mesangial cells of the renal cortex upon stimulation by hypoxia. Low iron increases production as it is a cofactor of HIFalpha dioxygenases

Question 27

What mediates EPO release?

Answer 27

Mediated by the release of PG HIF-2. | Mediated during shock or hypovolaemia with a low BP by beta-adrenoreceptor and ATII

Question 28

How is the response mediated by HIF-2 different to the response mediated by ATII?

Answer 28

During shock the aim is to increase volume to raise BP but it is slow and is not effective for acute shock.

Question 29

What is the purpose of administering an anti-apoptotic agent?

Answer 29

To ensure that all EPO progenitor cells survive to increase production.

Question 30

What is the mechanism of action of EPO?

Answer 30

EPO binds to receptors in the BM to increase the production of proerythroblasts. The EPO receptor activates JAK2 TK to activate the intracellular pathways Ras/MAP and STAT TF.

Question 31

What does low EPO receptor expression lead to?

Answer 31

Higher EPO concentration as EPO binding is irreversible as the receptors are internalised and removed from circulation. Therefore more EPO is needed to increase the chance of binding to the remaining receptors

Question 32

What may renal failure present with due to its endocrine functions?

Answer 32

ANAEMIA (normochromic normocytic) | Low 1,25 vitD (loss of conversion and diet restrictions)

Question 33

Why doesn't polycystic KD present with anaemia?

Answer 33

If enough parenchyma remains, EPO production is not lost as there is sufficient mesangial cells to continue producing.

Question 34

What is used to treat RF anaemia?

Answer 34

EPO analogues. They are modified to extend the half life via glycosylation

Question 35

Why is EPO abused in sport? What is the risk?

Answer 35

Used to increase endurance but carries an increases risk of thrombosis and reduced flow due to the increased haematocrit and viscosity.

Question 36

What is the role of the kidney in Vit D production?

Answer 36

Vit D from sun or diet is converted to 25 vitD in the liver and then to its active 1,25 vitD in the kidney.

Question 37

What controls Vit D activation in the kidney?

Answer 37

PTH stimulates | Calcitonin inhibits

Question 38

What is the effect of active vitD on the body?

Answer 38

Increases Ca and phosphate absorption in the small intestine and reduces excretion.

Question 39

Why can 25 vitD supplements be given to a pt with RF?

Answer 39

There are extrarenal areas in the body that have vitD hydroxylation functions

Question 40

What role does the renal system play in RAAS?

Answer 40

RENIN is secreted into the circulation from JG cells, upon a fall in BP. Acts at a distance to increase BP by vasoconstriction, increasing cortisol and aldosterone for Na and water retention.