Session 4 Flashcards by Ben Warren

Describe the distribution of water in the body

3L blood plasma + 11L interstitial fluid + 1L transcellular fluid (CSF/synovial) + 28L intracellular fluid = 42L total body water

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What determines the volume of water in the ECF?

Concentration of sodium

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Describe the percentage of filtered sodium that is reabsorbed in different parts of the nephron

PCT - 67
Descending limb - 0
Ascending limb - 25
DCT - ~5 (variable)
Collecting ducts - 3

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Describe the percentage of filtered water that is reabsorbed in different parts of the nephron

PCT - 60
Descending limb - 10-15
Ascending limb - 0
DCT - 0
Collecting ducts - 5-25

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What parts of the nephron is sodium reabsorption stimulated by RAAS and aldosterone?

RAAS - PCT

Aldosterone - DCT and CD

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What alters the proximal tubule sodium reabsorption (and hence water)?

Changes in osmotic/hydrostatic pressure in peritubular capillaries. Higher pressure -> less reabsorption

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Describe the process of pressure natriuresis and diuresis

Increase in renal artery blood pressure -> less Na/H antiporter and Na/K ATPase activity in PCT -> less water reabsorption -> increased water and sodium excretion
The increased peritubular capillary pressure also reduces fluid reabsorption.

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Where is chloride reabsorbed and why?

Late in the PCT. Removal of water increases its concentration to make a good gradient. Most reabsorption is paracellular and passive. Maintains overall electroneutrality after Na+ reabsorption.

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Describe the different apical channels in the different parts of the PCT

S1: Na/H antiporter, cotransport with glucose/AA/phosphate, aquaporin (created Cl gradient)
S2-S3: Na/H antiporter, paracellular and transcellular Cl, aquaporin

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List the driving forces for PCT water reabsorption

Osmotic gradient established by solute reabsorption
Hydrostatic force in interstitium
Oncotic force in peritubular capillaries due to loss of filtrate but remaining proteins and cells

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What is the second line of defence for changing GFR after autoregulation?

Glomerulotubular balance - blunts sodium excretion in response to any GFR changes. This maintains the 67% filtered sodium in the PCT and minimises changes in sodium concentration leaving the PCT.

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Describe what happens in each part of the LoH

Descending - no active transport and water moves out passively by osmosis driven by the concentration gradient down the medulla
Thin ascending - solute moves out passively
Thick ascending - impermeable to water and actively moves out solute (diluting segment)

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What channels are present in the apical membrane of the thick ascending limb of the LoH?

NKCC2

ROMK - K+ moves back into lumen to maintain Na/K ATPase and ROMK

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Describe what happens in the two regions of the DCT

DCT1- NCC symporter on apical membrane
DCT2 (similar to early CD) - NCC and ENaC. Electrochemical gradient drives Cl reabsorption
Filtrate become more and more hyposmotic as DCT has low water permeability

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Where and how is calcium reabsorbed from the tubule?

In the DCT. NCX (Na in, Ca out) on basolateral membrane creates a concentration gradient for Ca to enter apical membrane. Calbindin shuttles shuttles Ca between the membranes. All this is tightly regulated by hormones (e.g. PTH)

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What are the two regions of the collecting duct?

Cortical (CCD) and medullary (MCD)

What are the two cell types in the CCD?

Principle cells (70%) - reabsorption of sodium by ENaC
Intercalated cells - A-IC secreted H+ into lumen via H/K ATPase. B-IC secretes bicarbonate

What is the short term regulation of blood pressure and why is this no long term solution?

The baroreceptor reflex. The threshold for baroreceptor firing resets.

What are the 4 parallel neurohumoral pathways that control circulating volume and hence blood pressure?

RAAS
Sympathetic nervous system
ADH
Atrial natriuretic peptide (ANP)

What causes renin to be released by granular cells of the juxtaglomerular apparatus?

Reduced NaCl delivery to distal tubule
Reduced perfusion pressure in the kidney - sensed by baroreceptors in the afferent arteriole
Sympathetic stimulation to JGA

Outline the stages of the RAAS

Angiotensinogen -renin-> angiotensin I -ACE-> angiotensin II -> number of effects

List the actions of angiotensin II

Arterioles - vasoconstriction
Kidney - stimulates Na+ reabsorption (vasoconstriction of arterioles and stimulates NHE in PCT)
Sympathetic NS - increases release of NA
Adrenal cortex - stimulates aldosterone release
Hypothalamus - increased thirst sensation

List the actions of aldosterone

Increases expression of ENaC, apical K+ channels and Na/K ATPase of principle cells of collecting ducts to stimulate Na+ and hence water reabsorption.

What are the actions of angiotensin converting enzyme?

Converts ang. 1 to ang.2

Breaks down the vasodilator bradykinin

What are the effects of high levels of sympathetic stimulation to the kidneys?

Constricts afferent arteriole Activates NHE and Na/K ATPase in PCT Stimulates renin release from JG cells

Describe the action of ADH

Increases water reabsorption in distal nephron through AQP2 and increases NKCC2 activity in LoH

What stimulates ADH release?

Increase in plasma osmolarity or severe hypovolaemia

There is ANP released and what are its actions?

Released by arterial myocytes in response to stretch. Causes vasodilation of afferent arteriole and inhibits sodium reabsorption along the nephron

Why can NSAIDs lead to acute renal failure if administered when renal perfusion is compromised?

They inhibit prostaglandin production which normally buffer the excessive vasoconstriction caused by SNS and RAAS to maintain renal blood flow.

Define the different stages of hypertension

Stage 1: >140/90 Stage 2: >150/100 Severe: >160/110

Define primary and secondary hypertension

Primary (95%) - cause unknown, pathogenesis unclear. May be genetic or environmental. Secondary - a primary cause can be defined and treated. E.g. Cushings, renovascular disease, chronic renal disease, aldosteronism

How can renovascular disease lead to hypertension?

Renal artery stenosis -> decreased perfusion pressure -> renin production and activation of RAAS -> vasoconstriction and Na retention

Outline the adrenal causes of secondary hypertension

Conn's syndrome - aldosterone secreting adenoma Cushing' syndrome - excess cortisol acts and aldosterone receptors Phaechromocytoma (adrenal medulla) - secretes catecholamines

Name two agents that can be used to treat primary hypertension by targeting the RAAS

ACE inhibitors | Angiotensin II antagonist

Name two vasodilators that can be used the treat primary hypertension

L type Ca2+ blockers - reduce calcium entry into VSM causing them to relax Alpha 1 receptor antagonists

List some of the non pharmacological methods used to complement antihypertensive drugs

Exercise Diet Reduced salt intake Reduced alcohol intake