Command and Control Flashcards
How odes the macula densa cells interact with the systemic system?
-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)
What happens when there is a decrease in systemic pressure?
- 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
What are the effects of angiotensin 2?
- Direct arteriole vasoconstriction= increases bp by reducing available volume
- Increases sympathetic activity
- Increases NaCl reabsorption by tubules in the kidney
Describe the action of Angiotensin 2 on kidney cells
-In PCT cells, angiotensin receptors
=Sodium proton exchanger/antiporter on apical membrane increased activity
-Increases sodium uptake and increasing proton export
How does angiotensin 2 act on the adrenal gland?
-Makes cells in the cortex of gland secrete aldosterone hormone
What are the actions of aldosterone?
- 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)
What is the action of AVP?
-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
What effect does the sympathetic response have on renal nerves?
-Secretion of noradrenaline
=contracts both vessels serving the glomerulus
=reduce flow
-Directly promotes renin release
What is the ‘brake’ on the angiotensin system and its effect on blood pressure?
-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
What controls calcium ion concentration in the blood?
- Monitored by parathyroid glands
- Low blood free calcium= parathyroid hormone receptors on renal cells
What are the actions of parathyroid hormone on renal cells?
-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)
How are the kidneys involved in the control of acid-base balance?
-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
Describe the potassium control loop
- 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
What happens to potassium regulation if the body is in chronic alkalosis?
-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)
What happens to potassium regulation if the body is in acute acidosis?
-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
What happens to potassium regulation if the body is in chronic acidosis?
-Sodium pump becomes less effective in PCT
=urine more copious
=helps flush extra potassium away
Why do we want to clinically intervene in renal function?
-Control of hypertension Renin production -Control of oedema =fluid homeostasis -Control of ion imbalances =lose/recover -Control of acid-base disturbances =metabolic compensation
What is Diuresis?
-Through-flow of urine
-Diuretics increase through flow of urine
=Increasing the amount of water (+ salts) lost from the body
Mechanism of loop diuretics
-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
What are the features of loop diuretics?
-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
What is the main effect of loop diuretics on blood pressure?
-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
Example of alternative diuretics
- Distal tubule diuretic= thiazides
- Potassium-sparing diuretics (amiloride)
- Spironolactone
- Carbonic anhydrase inhibitors
- Osmotic agents (mannitol)
Describe thiazides
- Distal tubule (recovers less salt so less powerful)
- Block sodium and chloride cotransporter in distal tubule cells
Describe Potassium-sparing diuretics
-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
Describe Spironolactone
- 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
Describe Carbonic anhydrase inhibitors
-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
Describe osmotic agents
-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.
