Urinary 5

Question 1

The kidneys play a central role in maintaining blood pressure by doing which 3 things?

Answer 1

regulating salt and water excretion

controlling peripheral vascular tone

interacting with neurohormonal mechanisms

Question 2

Impaired kidney function can lead to what diseases?

Answer 2

hypertension and ESRD

Question 3

ECF volume includes what?

Answer 3

intravascular volume and ISF volume

Question 4

What is Frank-Starling’s Law?

Answer 4

CO = SV x HR -> more in means more out (the more the heart is filled, the harder it’ll squeeze)

(SV = EDV-ESV)

Question 5

What 5 things are BP influenced by?

Answer 5

Question 6

Fill in the gaps.

Answer 6

Question 7

How is blood pressure regulated (short-term)?

Answer 7

baroreceptors detect how stretch the vessel walls are = tells the brain about blood pressure

1. adjust sympathetic input to PERIPHERAL RESISTANCE VESSELS -> alters TPR
2. adjust parasympathetic and sympathetic input to HEART -> alters CO

Question 8

Explain what occurs when BP rises and falls (short-term).

Answer 8

Question 9

How is BP regulated long-term?

Answer 9

determined by ECF volume: primarily determined by the total amount of osmotically-active solute within the ECF

RAAS

Question 10

What is the primary determinant of ECF volume?

Answer 10

amount of Na+ in ECF

Na+ reabsorption in the kidneys is therefore the primary determinant of ECF volume

Question 11

Where does obligatory reabsorption of Na+ take place? Via which channels?

Answer 11

PCT - 65%
- basolateral Na+/K+ ATPases
- luminal Na+ channels

TAL of the loop of Henle - 25%
- Na+/K+/2CL- co-transporter

Question 12

How does tubular fluid get diluted in the TAL of the Loop of Henle?

Answer 12

1. Na+/K+/2CL- co-transporter on the apical (luminal) side of TAL cells = pulls 1 Na+, 1 K+ and 2 Cl- from TUBULAR FLUID AND INTO CELL (salt is reabsorbed but TAL is impermeable to water - fluid = DILUTE)
2. K+ diffuses back into the lumen via ROMK channels
3. positive lumen voltage -> as K+ leaves the cell back into lumen, lumen becomes slightly positive

Question 13

What maintains a positive charge in the TAL?

What does this allow?

Answer 13

the return of K+ into the TAL lumen

allows the paracellular reabsorption of Na+, Ca2+ and Mg2+ from the TAL

Question 14

Explain what is occurring.

Answer 14

Question 15

What type of medication is furosemide?

What does it act on?

Answer 15

loop diuretic

inhibits the Na+/K+/2Cl- co-transporter in the TAL (by competing for Cl-)

furosemide blocks NKCC2 = less Na+ reabsorbed, lumen voltage drops = less reabsorption of Ca2+ and Mg2+

water follows Na+ = increased urine output

Question 16

How does aldosterone facilitate maximal Na+ reabsorption during volume depletion?

Answer 16

promotes/stimulates ENaC expression in the late distal convoluted tubule and collecting duct

(ENaC is expressed on the apical membrane of principal cells)

Question 17

Where is ENaC expressed?

What does it do? How does it affect potassium?

Answer 17

on the apical (luminal) membrane of principal cells in the late distal convoluted tubule and collecting duct

allows sodium to enter the principal cell from tubular fluid = creates a negative electrical potential in the lumen -> negative lumen pulls K+ out of principal cells through potassium channels like ROMK into the lumen and potassium IS EXCRETED IN URINE

Question 18

What type of diuretic is Amiloride?

Answer 18

K+ sparing diuretic - acts by blocking ENaC

promotes sodium and water excretion but retain potassium

Question 19

Give two examples of potassium-sparing diuretics and explain their mechanism of action.

Give two examples of loop diuretics which cause hypokalemia.

Answer 19

1. aldosterone antagonist e.g SPIRONOLACTONE
   - block aldosterone receptors in principal cells = less ENaC expression = less Na+ reabsorbed - lumen less negative -> less K+ leaves
2. ENaC blockers e.g AMILORIDE
   - directly block ENaC channels in principal cells

loop diuretics
- furosemide
- bumetanide
(both inhibit Na+/K+/2Cl- in TAL)

Question 20

What are the 3 sensors involved in regulating ECF volume?

Answer 20

1. JUXTAGLOMERULAR APPARATUS (granular cells of the JGA release renin in response to low BP = initiate RAAS)
2. ATRIA (release natriuretic peptide to promote Na+ excretion)
3. CAROTID SINUS (regulates the activity of the sympathetic nervous system and relays hypovolemic stimulus to vasopressin)

Question 21

Where is renin released from? It is released in response to what?

Answer 21

from the granular cells of the JGA

released in response to low BP

Question 22

How is renin formed?

What is renin’s only function?

Answer 22

the biologically inactive precursor - PRORENIN - within the granules of the granular cells is cleaved to form RENIN

to cleave angiotensinogen to form angiotensin I

Question 23

What stimulates renin secretion?

Answer 23

1. low BP - sensed by cardiopulmonary baroreceptors
2. low BP - sensed by afferent arteriole baroreceptors
3. increased sympathetic activity via renal nerves

Question 24

What inhibits renin secretion?

Answer 24

1. increased Na+/Cl- reabsorption by macula densa cells of the early distal tubule
2. elevated BP in afferent arteriole
3. angiotensin II - negative-feedback
4. vasopressin

Question 25

How does Angiotensin II reverse low BP caused by hypovolaemia?

Answer 25

1. arteriolar vasoconstriction to increase systemic BP (vasoconstriction of efferent arterioles in glomerulus) 2. directly stimulating Na+ reabsorption to increase circulating volume and BP 3. indirectly stimulating Na+ reabsorption by stimulating release of aldosterone from adrenal cortex

Question 26

How does Angiotensin II directly and indirectly reverse low BP?

Answer 26

directly: stimulates Na+ reabsorption to increase circulating volume and increase BP (directly stimulates Na+ transporters) indirectly: stimulates Na+ reabsorption by stimulating release of aldosterone from adrenal cortex

Question 27

Where is aldosterone released from? What does it act on and how?

Answer 27

zona glomerulosa of the adrenal cortex acts on the principal cells of the DCT and collecting duct to stimulate Na+ reabsorption by stimulating expression of ENaC channels

Question 28

What is released if BP increases? What is released if BP decreases?

Answer 28

atrial natriuretic peptide (ANP) - from heart atrial cells = blocks renin secretion renin - from granular/juxtaglomerular cells of JGA

Question 29

What do atrial cells release which blocks renin secretion? What does this do?

Answer 29

atrial natriuretic peptide (ANP) inhibits expression of ENaC channels in principal cells - reduces Na+ reabsorption

Question 30

What causes the release of ANP and how?

Answer 30

high ECF volume = high venous pressure stretching of atria of the heart due to volume expansion causes release of ANP ANP acts on principal cells of the collecting duct to reduce Na+ reabsorption Na+ excretion = reduced ECF volume

Question 31

What is the main cation in plasma?

Answer 31

sodium

Question 32

What is the difference between diuresis and diuretic?

Answer 32

diuresis: increased formation of urine by the kidney diuretic: substance/drug that promotes diuresis

Question 33

What is the term for increased sodium excretion? What is the term for increased potassium excretion? What is the term for a substance that causes net excretion of water?

Answer 33

sodium: natriuresis potassium: kaliuresis water: aquaretics

Question 34

Diuretics blocking ENaC also reduce the secretion of what?

Answer 34

K+

Question 35

What diuretics act on what part?

Answer 35

blue: carbonic anhydrase inhibitors e.g ACETAZOLAMIDE blue/yellow: osmotic diuretics e.g MANNITOL red: loop diuretics e.g FUROSEMIDE green: thiazide diuretics e.g INDAPAMIDE grey: K+ sparing diuretics e.g SPIRANOLACTONE

Question 36

Where do carbonic anhydrase inhibitors act? Give an example.

Answer 36

proximal tubule they inhibit carbonic anhydrase -> reduce Na+/H+ exchange -> mild diuresis and bicarbonate loss e.g ACETAZOLAMIDE

Question 37

Where do osmotic diuretics act? Give an example.

Answer 37

mainly PCT and descending limb of loop of henle increase tubular osmolarity = water follows -> diuresis e.g MANNITOL

Question 38

Where do thiazide diuretics act? Give an example.

Answer 38

distal convoluted tubule - inhibits Na/Cl symporter METOLAZONE

Question 39

Where do loop diuretics act? Give an example.

Answer 39

loop of henle - TAL - inhibit Na/K/2Cl symporter FUROSEMIDE / BUMETANIDE

Question 40

Where do K+ sparing diuretics and aldosterone antagonists act?

Answer 40

collecting duct K+ sparing: AMILORIDE aldosterone: SPIRANOLACTONE

Question 41

What do carbonic anhydrase inhibitors do? Give an example of one. What can they cause? What are they used for?

Answer 41

inhibit action of carbonic anhydrase in PCT cell - ACETAZOLAMIDE metabolic acidosis due to loss of HCO3- in urine useful in the treatment of glaucoma

Question 42

What type of diuretic is Mannitol? What does it do and what is it used for?

Answer 42

osmotic diuretic increases plasma osmolarity thus drawing out fluid from tissues and cells IV mannitol - used to treat cerebral oedema

Question 43

What type of diuretics can cause hyperkalaemia?

Answer 43

K+ sparing diuretics and aldosterone antagonists

Question 44

What type of diuretic is Amiloride? What type of diuretic is Spironolactone?

Answer 44

potassium sparing diuretic aldosterone antagonist

Question 45

How does CHF result in oedema?

Answer 45

drop in CO - failing heart cannot pump effectively = blood backs up in the venous system -> increased venous pressure -> fluid leaks into tissues -> peripheral oedema low perfusion = RAAS activated -> worsens oedema

Question 46

What is the first line therapy for CHF?

Answer 46

loop diuretics - furosemide

Question 47

What occurs in nephrotic syndrome?

Answer 47

proteinuria - low plasma albumin -> low oncotic pressure = OEDEMA oedema -> reduced circulatory volume -> RAAS activated -> Na+ and water retention -> expansion of ECF and OEDEMA

Question 48

How does liver cirrhosis cause oedema?

Answer 48

Question 49

How does portal hypertension cause oedema?

Answer 49

Question 50

Fill in the gaps.

Answer 50