eLFH - Renal Physiology Part 3 Flashcards
Trigger for activation of Renin-Angiotensin-Aldosterone System (RAAS)
Fall in BP and thus fall in renal blood flow
Overview of RAAS
Fall in BP detected by juxtaglomerular apparatus
Juxtaglomerular apparatus secretes renin
Renin stimulates conversion of angiotensinogen to angiotensin
Angiotensin causes vasoconstriction + Aldosterone secretion from adrenal cortex
Aldosterone causes Na+ and water reabsorption
Juxtaglomerular apparatus structure and components
Macula Densa
Juxtaglomerular cells
Macula Densa
Specialised epithelial cells
Increase renin release in response to low levels of delivered sodium due to fall in GFR or increase in proximal convoluted tubule reabsorption of Na+
Location of Macula Densa
Wall of first part of distal convoluting tubule
Abuts the afferent and efferent arterioles
Juxtaglomerular cells role
Secrete renin from granules
Location of juxtaglomerular cells
Wall of afferent arteriole (in the media)
Just before arteriole enters the glomerulus
Triggers for juxtaglomerular cells to secrete renin
Hypovolaemia
Increased sodium concentration in blood
Sympathetic stimulation
Features of Renin
Glycoprotein hormone
Formed from pro-renin and pre-pro-renin
Half life of renin
80 mins
Control of renin secretion
Renal sympathetic nerves
Intrarenal baroreceptors
Angiotensin II
Factors which increase renin secretion
Hypovolaemia
Cardiac failure
Cirrhosis
Renal artery stenosis
Catecholamines acting on beta 1 receptors
Factors which decrease renin secretion
Angiotensin II
Vasopressin
Beta blockers
Actions of renin
Cleaves Angiotensin I from Angiotensinogen
Angiotensin I converted to Angiotensin II by ACE in lungs / capillary endothelium
Angiotensin II converted to Angiotensin III in many tissues by aminopeptidase
Actions of angiotensin II
Vasoconstrictor including afferent and efferent arterioles in kidney
Greater effect on efferent arteriole than afferent arteriole - increases GFR
Aldosterone release
Potentiates sympathetic activity
Release of ADH
Thirst by direct effect on hypothalamus
Stimulates Na+/H+ antiporters in proximal convoluting tubule to cause Na+ and water retention
Triggers for aldosterone release from zona glomerulosa of adrenal cortex
Reduced renal blood flow via RAAS
Stress and trauma via ACTH release
Hyperkalaemia
Hyponatraemia
Time of onset of aldosterone action and why
Hours
As works via protein synthesis
Actions of aldosterone on distal convoluting tubules and collecting ducts
Increases sodium reabsorption and thus water reabsorption
Potassium and hydrogen ions are lost in exchange for Na+
Increases production of distal nephron transport mechanisms
Site of ADH synthesis
Hypothalamus
Site of ADH secretion
Posterior pituitary
Factors which lead to ADH secretion
Baroreceptor and Osmoreceptor reflexes
Inactivation site for ADH and half life
Inactivated in liver and kidney
Half life 18 mins
Action of ADH on renal tubule
Inserts protein channels for water (aquaporins) into luminal membrane
Acts via cyclic AMP
Action of ADH on arteriolar smooth muscle
At high concentrations of ADH, it causes arteriolar smooth muscle contraction
Reduces renal blood flow and GFR
Also increases MAP, hence use as second line vasopressor
Role of ANP (atrial natriuretic peptide)
Secreted in response to atrial stretch
Increases renal excretion of Na+ and water
Mechanism of action of ANP
Afferent arteriolar dilatation and efferent arteriolar constriction - increases net filtration pressure and renal blood flow
Inhibition of renin secretion and therefore inhibition of aldosterone release
Direct action on collecting ducts to decrease sodium reabsorption
Site of ANP release
Atrial myocytes
Diagram with whole RAAS illustrated
Glomerular filtration rate definition
Flow rate of filtered fluid through the kidneys
Normal value for adult GFR
180 L/day
aka
125 ml/min
Renal Clearance definition
Volume of plasma completely cleared of that substance by the kidneys per unit time (ml/min)
Use of clearance
Help quantify:
- Excretory function of kidney
- Rate of blood flow through kidneys
- Basic functions of the kidneys
Clearance of certain substances can be used to approximate GFR
Clearance equation
Substances used to measure GFR
Inulin
Creatinine
Features of Inulin including molecular weight
Polysaccharide
Molecular weight 5200 Daltons
Reasons Inulin is used to measure GFR
Freely filtered but not reabsorbed
Not toxic, metabolised or protein bound - therefore rate of excretion is equal to filtration rate
Issues with using inulin
Not endogenous and needs IV administration
Features of creatinine
By product of muscle metabolism - therefore endogenous
Almost entirely cleared by glomerular filtration
Therefore creatinine clearance can estimate GFR
Issues with using creatinine
Small amount is secreted
Therefore amount of creatinine excreted slightly exceeds amount filtered
Therefore overestimates GFR
Renal plasma flow estimation
If a substance is completely cleared from the plasma, clearance of that substance should equal renal plasma flow
GFR is only 20% of renal plasma flow
Substance used to estimate renal plasma flow and why
Para-aminohippuric acid (PAH)
It is 90% cleared by kidneys from plasma
Renal plasma flow estimate equation
Renal blood flow equation
Renal Blood flow = Renal Plasma flow / (1 - Haematocrit)
