Manipulating renal physiology

Question 1

What is the nephron?

Answer 1

= functional unit of kidney

• glomerulus and bowman’s capsule
• PCT
• loop of henle and vasa recta
• DCT
• connecting tubule, collecting tubule (cortical and medullary parts), collecting duct

Question 2

Describe the glomerulus

Answer 2

• 2 sets capillaries in series (afferent and efferent arterioles either side of 1st capillary bed)
• high pressure glomerular capillaries
• glomerular BM
• podocytes in visceral epithelium

Question 3

Function - PCT

Answer 3

• returns 70% filtered load to plasma
• relatively no selective absorption
• sodium cotransport to glucose, aa, hydrogen ions (bicarbonate reabsorption), phosphate (regulated by PTH and FGF-23), chloride flux (b/w cells), water follows passively

Question 4

Function - Look of henle

Answer 4

• countercurrent mechanism to generate concentrated medulla
• thick ascending limb actively transports Na, K, Cl out of tubule, impermeable to water
• vasa recta for maintaining concentration gradient
• hypotonic fluid leaves loop and enters DCT

Question 5

Where does macula densa pass?

Answer 5

right next to the afferent arteriole

Question 6

Function - macula densa

Answer 6

• senses amount of chloride passing per unit time
• signals to glomerulus
• glomerular-tubular feedback
• control of GFR

Question 7

Where is renine secreted from?

Answer 7

modified SMC of afferent arteriole

Question 8

Causes - renin secretion

Answer 8

• reduced stretch of SMC
• signals from MD
• SNS

Question 9

Function - renin

Answer 9

Cleaves angiotensinogen –> Ang 1 (cleaved by ACE) –> Ang 2

Question 10

Functions Ang2

Answer 10

• constricts efferent aa
• enhances Na and H20 absorption from PCT
• stimulates aldosterone secretion

Question 11

What effects will ACE inhibitors (benazepril) or Ang2 receptor blockers (telmisartan) have on the kidney?

Answer 11

aaa

Question 12

Functions - DCT

Answer 12

• fine regulation of urine composition

- site of action of aldosterone (salt retaining hormone regulates the amount of Na reabsorbed and K excreted)

Question 13

What does aldosterone do?

Answer 13

• more apical membrane Na sodium channels
• more basolateral sodium pumps
• more apical K channels

Question 14

Function DCT

Answer 14

sitei iof fine control of acid-base balance - regenerating bicarbonate used as a buffer by the body (carbonic anhydrase required)

Question 15

What are hydrogen ions buffered by?

Answer 15

phosphate - net bicarbonate is reclaimed

Question 16

Function - PTH

Answer 16

• regulates reabsorption of CA in DCT ensuring right amount is excreted
• actions on phosphate reabsorption occur in the PCT

Question 17

Function - connecting tubule, collecting tubule and collecting duct

Answer 17

• sensitive to ADH (increases number of water channels in epithelium and enhances urea permeability - part of concentrating method of kidney)
• water reabsorpbed if ADH present
• urea recycle and is part of concentration gradient

Question 18

Action - diuretics

Answer 18

inhibit sodium chloride reabsorption to increase salt and water reabsorption. This counter-acts salt and water retention in HF. Body activates renin secretion.

Question 19

Action - loop diuretics

Answer 19

act on ascending LoH from tubule side

Question 20

How do loop diuretics reach site of action?

Answer 20

by PCT secretion as heavily plasma protein bound

Question 21

Action furosemide

Answer 21

• pulmonary venodilator action when given IV (excellent if animal is drowning from pulmonary congestion as action is much faster than can be explained from kidney effects)

Question 22

Onset, peak and duraton - furosemide

Answer 22

• 5 mins after IV, peak effet 30 min, duration 2 hours

- 60 mins after oral, peak effect 2 hours, duration 6 hours

Question 23

T/F: up to 25% filtered load can be lost with a loop diuretic eg. furosemide

Answer 23

true

Question 24

Site of action - thiazine diuretics

Answer 24

early DCT

Question 25

Kidney functions

Answer 25

- excrete nitrogenous waste and xenobiotics - regulate water, electrolyte, mineral and acid base - produces active hormones (calcitriol, EPO)

Question 26

What do thiazide diuretics bind to?

Answer 26

Cl- site of the Na+/Cl- co-transporter

Question 27

Are thiazide diuretics more efficacious than loop diuretics?

Answer 27

Less - promote up to 10% loss of filtered load

Question 28

What is the effect of thiazide diuretics on Ca?

Answer 28

Promote Ca retention in human patients - unlike loop diuretics

Question 29

Which thiazide diuretics are used in dogs?

Answer 29

chlorothiazide and hydrochlorthiazide

Question 30

Outline action of thiazide diuretics

Answer 30

- orally active - onset of action within 1 hr - peak at 4 hours - duration 6-12 hours

Question 31

Do thiazide diuretics have anti-hypertensive effects?

Answer 31

yes - effects include vascular action

Question 32

Action - K+ sparing diuretics

Answer 32

act on collecting tubule to inhibit the action of aldosteroine

Question 33

Action - spironolactone

Answer 33

competitive antagonist of aldosterone

Question 34

Action - trimaterene and amiloride

Answer 34

non-competitive inhibitors of aldosterone

Question 35

Potential adverse effect of K+ sparing diuretics

Answer 35

hyperkalaemia

Question 36

How strong a diuretic are K+ sparing diuretics?

Answer 36

weak diuretics in own right - mainly used to prevent K+ loss

Question 37

General adverse effects of diuretics

Answer 37

- volume contraction --> circulatory impairment | - synergistic with vasodilators which reduce preload

Question 38

How to avoid adverse effects of diuretics

Answer 38

- identify cases which are pre-load dependent - monitor: HR, BP and mm strength - reduce dose after congestion resolves

Question 39

Adverse effect - furosemide

Answer 39

hypokalaemia

Question 40

Adverse effect - thiazides

Answer 40

hypomagnesaemia

Question 41

Why are hypokalaemia and hypomagnesaemia important for heart failure patients?

Answer 41

predispose cardiac arrhythmias

Question 42

Which diuretics might cause hyponatraemia?

Answer 42

all diuretics potentially, there is a poor prognosis if this is seen (d/t low ADH secretion, usually seen in refractory HF)

Question 43

Which diuretics might cause hypochloraemic metabolic alkalosis?

Answer 43

furosemide and thiazide diuretics

Question 44

What is torasemide?

Answer 44

Newly licensed loop diuretic - a more potent furosemide

Question 45

What are the general considerations for diuretic drugs?

Answer 45

ROA will determine: - onset of action (IV rapid) - duration (IV shorter) - bioavailability (orally administered drugs may be poorly absorbed in face of right-sided HF)

Question 46

What drug interactions may occur with diuretics?

Answer 46

- diuretics are synergistic with vasodilators (reduce preload) - reduce the dose once congestion resolves - renal prostaglandins are natriuretic - NSAIDs exacerbate salt and water retention in HF thus reducing diuretic efficacy (COX-1 and COX-2 inhibition)

Question 47

Summarise efficacy and duration of loop diuretic action

Answer 47

loop diuretics are most effective but relatively short acting

Question 48

Which combinations of diuretics are synergistic?

Answer 48

- loop + thiazide | - loop/thiazide + potassium sparing