Session 4

Question 1

Describe the distribution of water in the body

Answer 1

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

Question 2

What determines the volume of water in the ECF?

Answer 2

Concentration of sodium

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

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

Answer 5

RAAS - PCT

Aldosterone - DCT and CD

Question 6

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

Answer 6

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

Question 7

Describe the process of pressure natriuresis and diuresis

Answer 7

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.

Question 8

Where is chloride reabsorbed and why?

Answer 8

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.

Question 9

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

Answer 9

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

Question 10

List the driving forces for PCT water reabsorption

Answer 10

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

Question 11

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

Answer 11

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.

Question 12

Describe what happens in each part of the LoH

Answer 12

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)

Question 13

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

Answer 13

NKCC2

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

Question 14

Describe what happens in the two regions of the DCT

Answer 14

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

Question 15

Where and how is calcium reabsorbed from the tubule?

Answer 15

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)

Question 16

What are the two regions of the collecting duct?

Answer 16

Cortical (CCD) and medullary (MCD)

Question 17

What are the two cell types in the CCD?

Answer 17

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

Question 18

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

Answer 18

The baroreceptor reflex. The threshold for baroreceptor firing resets.

Question 19

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

Answer 19

RAAS
Sympathetic nervous system
ADH
Atrial natriuretic peptide (ANP)

Question 20

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

Answer 20

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

Question 21

Outline the stages of the RAAS

Answer 21

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

Question 22

List the actions of angiotensin II

Answer 22

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

Question 23

List the actions of aldosterone

Answer 23

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

Question 24

What are the actions of angiotensin converting enzyme?

Answer 24

Converts ang. 1 to ang.2

Breaks down the vasodilator bradykinin

Question 25

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

Answer 25

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

Question 26

Describe the action of ADH

Answer 26

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

Question 27

What stimulates ADH release?

Answer 27

Increase in plasma osmolarity or severe hypovolaemia

Question 28

There is ANP released and what are its actions?

Answer 28

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

Question 29

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

Answer 29

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

Question 30

Define the different stages of hypertension

Answer 30

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

Question 31

Define primary and secondary hypertension

Answer 31

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

Question 32

How can renovascular disease lead to hypertension?

Answer 32

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

Question 33

Outline the adrenal causes of secondary hypertension

Answer 33

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

Question 34

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

Answer 34

ACE inhibitors

Angiotensin II antagonist

Question 35

Name two vasodilators that can be used the treat primary hypertension

Answer 35

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

Question 36

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

Answer 36

Exercise
Diet
Reduced salt intake
Reduced alcohol intake