Manipulating renal physiology Flashcards
What is the nephron?
= 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
Describe the glomerulus
- 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
Function - PCT
- 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
Function - Look of henle
- 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
Where does macula densa pass?
right next to the afferent arteriole
Function - macula densa
- senses amount of chloride passing per unit time
- signals to glomerulus
- glomerular-tubular feedback
- control of GFR
Where is renine secreted from?
modified SMC of afferent arteriole
Causes - renin secretion
- reduced stretch of SMC
- signals from MD
- SNS
Function - renin
Cleaves angiotensinogen –> Ang 1 (cleaved by ACE) –> Ang 2
Functions Ang2
- constricts efferent aa
- enhances Na and H20 absorption from PCT
- stimulates aldosterone secretion
What effects will ACE inhibitors (benazepril) or Ang2 receptor blockers (telmisartan) have on the kidney?
aaa
Functions - DCT
- fine regulation of urine composition
- site of action of aldosterone (salt retaining hormone regulates the amount of Na reabsorbed and K excreted)
What does aldosterone do?
- more apical membrane Na sodium channels
- more basolateral sodium pumps
- more apical K channels
Function DCT
sitei iof fine control of acid-base balance - regenerating bicarbonate used as a buffer by the body (carbonic anhydrase required)
What are hydrogen ions buffered by?
phosphate - net bicarbonate is reclaimed
Function - PTH
- regulates reabsorption of CA in DCT ensuring right amount is excreted
- actions on phosphate reabsorption occur in the PCT
Function - connecting tubule, collecting tubule and collecting duct
- 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
Action - diuretics
inhibit sodium chloride reabsorption to increase salt and water reabsorption. This counter-acts salt and water retention in HF. Body activates renin secretion.
Action - loop diuretics
act on ascending LoH from tubule side
How do loop diuretics reach site of action?
by PCT secretion as heavily plasma protein bound
Action furosemide
- 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)
Onset, peak and duraton - furosemide
- 5 mins after IV, peak effet 30 min, duration 2 hours
- 60 mins after oral, peak effect 2 hours, duration 6 hours
T/F: up to 25% filtered load can be lost with a loop diuretic eg. furosemide
true
Site of action - thiazine diuretics
early DCT
Kidney functions
- excrete nitrogenous waste and xenobiotics
- regulate water, electrolyte, mineral and acid base
- produces active hormones (calcitriol, EPO)
What do thiazide diuretics bind to?
Cl- site of the Na+/Cl- co-transporter
Are thiazide diuretics more efficacious than loop diuretics?
Less - promote up to 10% loss of filtered load
What is the effect of thiazide diuretics on Ca?
Promote Ca retention in human patients - unlike loop diuretics
Which thiazide diuretics are used in dogs?
chlorothiazide and hydrochlorthiazide
Outline action of thiazide diuretics
- orally active
- onset of action within 1 hr
- peak at 4 hours
- duration 6-12 hours
Do thiazide diuretics have anti-hypertensive effects?
yes - effects include vascular action
Action - K+ sparing diuretics
act on collecting tubule to inhibit the action of aldosteroine
Action - spironolactone
competitive antagonist of aldosterone
Action - trimaterene and amiloride
non-competitive inhibitors of aldosterone
Potential adverse effect of K+ sparing diuretics
hyperkalaemia
How strong a diuretic are K+ sparing diuretics?
weak diuretics in own right - mainly used to prevent K+ loss
General adverse effects of diuretics
- volume contraction –> circulatory impairment
- synergistic with vasodilators which reduce preload
How to avoid adverse effects of diuretics
- identify cases which are pre-load dependent
- monitor: HR, BP and mm strength
- reduce dose after congestion resolves
Adverse effect - furosemide
hypokalaemia
Adverse effect - thiazides
hypomagnesaemia
Why are hypokalaemia and hypomagnesaemia important for heart failure patients?
predispose cardiac arrhythmias
Which diuretics might cause hyponatraemia?
all diuretics potentially, there is a poor prognosis if this is seen (d/t low ADH secretion, usually seen in refractory HF)
Which diuretics might cause hypochloraemic metabolic alkalosis?
furosemide and thiazide diuretics
What is torasemide?
Newly licensed loop diuretic - a more potent furosemide
What are the general considerations for diuretic drugs?
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)
What drug interactions may occur with diuretics?
- 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)
Summarise efficacy and duration of loop diuretic action
loop diuretics are most effective but relatively short acting
Which combinations of diuretics are synergistic?
- loop + thiazide
- loop/thiazide + potassium sparing
