Command and Control

Question 1

How odes the macula densa cells interact with the systemic system?

Answer 1

-Causes Juxtaglomerular cells to release renin hormone
=salt too low in DCT so blood flow may be too slow so blood pressure may be too low
-Do not when macula densa cells pumping out large amounts of NaCl (inhibits juxtaglomerular cells from releasing renin)

Question 2

What happens when there is a decrease in systemic pressure?

Answer 2

• Reduction of filtration rate (decrease in renal perfusion)
• Juxtaglomerular cells release
• Converts angiotensinogen (made by liver) into angiotensin 1
• Converted into angiotensin 2 by angiotensin converting enzyme (ACE) in lungs

Question 3

What are the effects of angiotensin 2?

Answer 3

• Direct arteriole vasoconstriction= increases bp by reducing available volume
• Increases sympathetic activity
• Increases NaCl reabsorption by tubules in the kidney

Question 4

Describe the action of Angiotensin 2 on kidney cells

Answer 4

-In PCT cells, angiotensin receptors
=Sodium proton exchanger/antiporter on apical membrane increased activity
-Increases sodium uptake and increasing proton export

Question 5

How does angiotensin 2 act on the adrenal gland?

Answer 5

-Makes cells in the cortex of gland secrete aldosterone hormone

Question 6

What are the actions of aldosterone?

Answer 6

• Acts on gene transcription of proton export system in type A cells (proton ATPase)= more mRNA so more proton ATPases
• Acts of transcription gene of ASC (amiloride-sensitive channel) in collecting ducts principal cells= allows sodium to come into the cell from apical domain where urine is then removed from cell by ATPase (basal)

Question 7

What is the action of AVP?

Answer 7

-Causes aquaporins to be moved from storage vesicles onto plasma membrane so water can be reabsorbed from collecting duct
=Increases total volume of fluid in the body
=Raises blood pressure

Question 8

What effect does the sympathetic response have on renal nerves?

Answer 8

-Secretion of noradrenaline
=contracts both vessels serving the glomerulus
=reduce flow
-Directly promotes renin release

Question 9

What is the ‘brake’ on the angiotensin system and its effect on blood pressure?

Answer 9

-ANP (atrial natriuretic peptide) from the heart responds if pressure gets too high
=ANP blocks activity of sodium reuptake channel in collecting duct and encourages loss of sodium

Question 10

What controls calcium ion concentration in the blood?

Answer 10

• Monitored by parathyroid glands

- Low blood free calcium= parathyroid hormone receptors on renal cells

Question 11

What are the actions of parathyroid hormone on renal cells?

Answer 11

-Increases activity of uptake channel TrpV5 that brings calcium back in from urine (+flow through leaky junctions of PCT)
=Moved across cell via calcium binding protein Calbindin
=Export channel increased in activity
*Calbindin and export channel need Vitamin D for synthesis
-Blocks activity of sodium and phosphate re-uptake channels in proximal tubule to allow more free calcium (insoluble calcium phosphate)

Question 12

How are the kidneys involved in the control of acid-base balance?

Answer 12

-Oxidation of food creates acidity (CO2)
-Automatic system if pH inside cell falls feedback loop
=apical sodium and proton exchangers more active
=Protons excreted into urine

Question 13

Describe the potassium control loop

Answer 13

• 90% of potassium reabsorption happens anyway
• Collecting duct intercalated cells constantly resorb potassium (antiporter protons out K+ in)
• Collecting duct principal cells have regulated excretion of K+= can be removed from membrane to reduce potassium loss/ too high and accumulates in cell

Question 14

What happens to potassium regulation if the body is in chronic alkalosis?

Answer 14

-Link between proton export and potassium recovery in intercalated cells
=Not many protons to export in alkalosis
=Antiporter activity slow so K+ recovery slow so less recovery (less H+ out-pumping)
=Hypokalemia (as principle cell exporter also increases in activity)

Question 15

What happens to potassium regulation if the body is in acute acidosis?

Answer 15

-H+ out-pumping by
intercalated cells increases so K+ reuptake
increases.
-Also, apical K+ channels on
Principal cells less active (by an effect on their intracellular regulation) so K+ secretion falls.
=Hyperkalemia

Question 16

What happens to potassium regulation if the body is in chronic acidosis?

Answer 16

-Sodium pump becomes less effective in PCT
=urine more copious
=helps flush extra potassium away

Question 17

Why do we want to clinically intervene in renal function?

Answer 17

-Control of hypertension
Renin production
-Control of oedema
=fluid homeostasis
-Control of ion imbalances
=lose/recover
-Control of acid-base disturbances
=metabolic compensation

Question 18

What is Diuresis?

Answer 18

-Through-flow of urine
-Diuretics increase through flow of urine
=Increasing the amount of water (+ salts) lost from the body

Question 19

Mechanism of loop diuretics

Answer 19

-Blocks SLC12A2 activity in thick ascending limb of loop of Henle (Na+, K+, Cl-)
=Stop salt being moved into interstitium
=less hypertonic area in medulla so less water recovered

Question 20

What are the features of loop diuretics?

Answer 20

-They are powerful (up to 20% of filtrate to
bladder: usually around 0.4%) +ve
-They result in loss of Na+
, K+ and Cl- because of
failure to recover in the TAL of LoH (-ve)
-They can result in hypercalciuria – less pull for
Ca2+ recovery – and kidney stones
-More Na+ getting to the Coll Duct means more
uptake there and more K+
loss

Question 21

What is the main effect of loop diuretics on blood pressure?

Answer 21

-The main effect on blood pressure is NOT
due to fluid loss (the patient will of course
detect that and drink more water).
-It is the effect of urine being unusually salty
at the distal tubule
=more NaCl in macula densa
=Inhibits renin release

Question 22

Example of alternative diuretics

Answer 22

• Distal tubule diuretic= thiazides
• Potassium-sparing diuretics (amiloride)
• Spironolactone
• Carbonic anhydrase inhibitors
• Osmotic agents (mannitol)

Question 23

Describe thiazides

Answer 23

• Distal tubule (recovers less salt so less powerful)

- Block sodium and chloride cotransporter in distal tubule cells

Question 24

Describe Potassium-sparing diuretics

Answer 24

-Act on collecting duct cells, amiloride-sensitive channel
=Act on uptake channel in same cells as potassium export channel so sodium=potassium ATPase short of sodium to pump out the cell

Question 25

Describe Spironolactone

Answer 25

• Interferes with ability of aldosterone to signal to cells
• ASC gene not transcribed efficiently so less sodium taken up
• Side effect= anti-androgen so gynaecomastia in male patients

Question 26

Describe Carbonic anhydrase inhibitors

Answer 26

-More bicarbonate in the lumen
=osmotic effect of resisting the egress of water from the PCT (leaky junctions)
-Less bicarbonate moving back into body= less water movement

Question 27

Describe osmotic agents

Answer 27

-Mannitol stays in lumen and resists water egress
-Very high plasma glucose has same effect
=if not all recovered from PCT= less water recovery
=Very high plasma glucose can exceed recovery capacity and act in this way: diabetic thirst because water lost but Na+ not lost as much -> hypernatremia.