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Renal > Manipulating renal physiology > Flashcards

Manipulating renal physiology Flashcards

1
Q

What is the nephron?

A

= 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
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2
Q

Describe the glomerulus

A
  • 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
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3
Q

Function - PCT

A
  • 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
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4
Q

Function - Look of henle

A
  • 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
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5
Q

Where does macula densa pass?

A

right next to the afferent arteriole

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6
Q

Function - macula densa

A
  • senses amount of chloride passing per unit time
  • signals to glomerulus
  • glomerular-tubular feedback
  • control of GFR
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7
Q

Where is renine secreted from?

A

modified SMC of afferent arteriole

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8
Q

Causes - renin secretion

A
  • reduced stretch of SMC
  • signals from MD
  • SNS
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9
Q

Function - renin

A

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

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10
Q

Functions Ang2

A
  • constricts efferent aa
  • enhances Na and H20 absorption from PCT
  • stimulates aldosterone secretion
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11
Q

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

A

aaa

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12
Q

Functions - DCT

A
  • fine regulation of urine composition

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

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13
Q

What does aldosterone do?

A
  • more apical membrane Na sodium channels
  • more basolateral sodium pumps
  • more apical K channels
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14
Q

Function DCT

A

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

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15
Q

What are hydrogen ions buffered by?

A

phosphate - net bicarbonate is reclaimed

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16
Q

Function - PTH

A
  • regulates reabsorption of CA in DCT ensuring right amount is excreted
  • actions on phosphate reabsorption occur in the PCT
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17
Q

Function - connecting tubule, collecting tubule and collecting duct

A
  • 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
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18
Q

Action - diuretics

A

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

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19
Q

Action - loop diuretics

A

act on ascending LoH from tubule side

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20
Q

How do loop diuretics reach site of action?

A

by PCT secretion as heavily plasma protein bound

21
Q

Action furosemide

A
  • 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)
22
Q

Onset, peak and duraton - furosemide

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

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

23
Q

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

A

true

24
Q

Site of action - thiazine diuretics

A

early DCT

25
Q

Kidney functions

A
  • excrete nitrogenous waste and xenobiotics
  • regulate water, electrolyte, mineral and acid base
  • produces active hormones (calcitriol, EPO)
26
Q

What do thiazide diuretics bind to?

A

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

27
Q

Are thiazide diuretics more efficacious than loop diuretics?

A

Less - promote up to 10% loss of filtered load

28
Q

What is the effect of thiazide diuretics on Ca?

A

Promote Ca retention in human patients - unlike loop diuretics

29
Q

Which thiazide diuretics are used in dogs?

A

chlorothiazide and hydrochlorthiazide

30
Q

Outline action of thiazide diuretics

A
  • orally active
  • onset of action within 1 hr
  • peak at 4 hours
  • duration 6-12 hours
31
Q

Do thiazide diuretics have anti-hypertensive effects?

A

yes - effects include vascular action

32
Q

Action - K+ sparing diuretics

A

act on collecting tubule to inhibit the action of aldosteroine

33
Q

Action - spironolactone

A

competitive antagonist of aldosterone

34
Q

Action - trimaterene and amiloride

A

non-competitive inhibitors of aldosterone

35
Q

Potential adverse effect of K+ sparing diuretics

A

hyperkalaemia

36
Q

How strong a diuretic are K+ sparing diuretics?

A

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

37
Q

General adverse effects of diuretics

A
  • volume contraction –> circulatory impairment

- synergistic with vasodilators which reduce preload

38
Q

How to avoid adverse effects of diuretics

A
  • identify cases which are pre-load dependent
  • monitor: HR, BP and mm strength
  • reduce dose after congestion resolves
39
Q

Adverse effect - furosemide

A

hypokalaemia

40
Q

Adverse effect - thiazides

A

hypomagnesaemia

41
Q

Why are hypokalaemia and hypomagnesaemia important for heart failure patients?

A

predispose cardiac arrhythmias

42
Q

Which diuretics might cause hyponatraemia?

A

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

43
Q

Which diuretics might cause hypochloraemic metabolic alkalosis?

A

furosemide and thiazide diuretics

44
Q

What is torasemide?

A

Newly licensed loop diuretic - a more potent furosemide

45
Q

What are the general considerations for diuretic drugs?

A

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)
46
Q

What drug interactions may occur with diuretics?

A
  • 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)
47
Q

Summarise efficacy and duration of loop diuretic action

A

loop diuretics are most effective but relatively short acting

48
Q

Which combinations of diuretics are synergistic?

A
  • loop + thiazide

- loop/thiazide + potassium sparing

Renal (30 decks)

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