- Renal blood flow
- Measurement of renal blood flow
- Renal autoregulation
- When do juxtaglomerular cells release renin?
- The renin angiotensin aldosterone system
- Eicosanoids and their relation to the kidney
Renin = hormone released from granular cells of the juxta-glomerular apparatus.
The juxtaglomerular cells form part of the afferent arteriole as it enters the glomerulus and are supplied by sympathetic nerves. They contain prorenin, which is converted to the acid protease renin before systemic release.
The macula densa is a region of cells at the start of the distal convoluted tubule, which lie adjacent to the juxtaglomerular cells of the same nephron.
Agranular lacis cells, which are renal epithelial cells lie between the afferent and efferent arterioles adjacent to the glomerulus.
These three components form the juxtaglomerular apparatus.
Function of the juxtaglomerular apparatus = regulate renal blood flow and glomerular filtration rate
Renal blood flow
Quick facts: Renal blood flow = 20% cardiac output, 1000ml/min, of which more goes to the glomerulus than medulla.
Renal blood flow is kept constant over MAP 75-165 by autoregulation.
If renal blood flow is too high = end organ high pressure damage, pressure diuresis (too quick for reabsorption to take place)
If renal blood flow is too low = ischaemia especially of the medulla and metabolically active PCT, and build up of toxins in blood due to reduced filtration
Renal blood flow measurement
Paraaminohippuric acid (PAH) – small enough to be freely filtered, secreted into tubules.
Renal plasma flow calculated by PAH clearance.
PAH amount entering the kidney should = PAH amount in urine
Renal plasma flow approximately = clearance of PAH
Renal plasma flow can give you renal blood flow via the following:
Renal blood flow = renal plasma flow / 1 – haematocrit
You can also measure renal blood flow by cannulating the renal artery and vein and sampling PAH concentration in each and applying Fick’s principle – obviously too invasive!
Methods of auto regulation:
- Tubuloglomerular feedback
of the afferent and efferent arterioles.
Constriction of afferent/efferent = increased overall renal vascular resistance = reduced renal blood flow
Constriction of afferent only = lower glomerular capillary hydrostatic pressure = reduced GFR
Constriction of efferent only = increased glomerular capillary hydrostatic pressure = increased GFR
Myogenic (>50% of auto regulation capability, fast response):
Arteriole stretches -> Mechanically gated non specific cation channels open -> depolarisation of arteriolar membrane -> smooth muscle contraction -> reduces vessel diameter -> vascular resistance increases -> renal blood flow constant.
Inadequate perfusion pressure in arteriole -> no depolarisation of arteriolar membrane -> smooth muscle relaxation -> increased vessel diameter -> vascular resistance decreases -> renal blood flow constant
Tubuloglomerular feedback (25-30% auto regulation capability, slow response):
Increase in renal perfusion pressure -> increased GFR -> increased Na + and Cl- ions delivered to macula densa -> Na+ and Cl- goes through Na+/K+/2Cl- cotransporters of macula densa, bringing water with them by osmosis -> macula densa cell swells in proportion to GFR -> cell releases an adenosine-based secondary messenger which acts at adenosine A1 receptors in the juxtaglomerular apparatus.
This leads to:
- Constriction of afferent arterioles -> increased renal vascular resistance -> reduced renal blood flow
- Contraction of glomerular mesangial cells -> reduced surface area for filtration -> reduced GFR
- Inhibition of renin secretion by juxtaglomerular cells
When do the juxtaglomerular cells release renin?
- Reduced tubular flow sensed by the macula densa
- Low afferent arteriolar pressure
- Sympathetic nervous system stimulation through Beta 1 adrenoceptors
The renin-angiotensin-aldosterone system in a thousand words
Why are NSAIDS bad for the kidneys?
In situations such as haemorrhage + sepsis where concentrations of circulating vasopressors eg noradrenaline + angiotensin II are high, there is a prolonged afferent and efferent arteriolar vasoconstriction -> a high renovascular resistance -> a low renal blood flow. (Risk of ischaemia to kidneys).
Vasodilatory prostaglandins PGE2 and PGI2 are released by the arteriolar cell membranes to oppose the vasoconstriction effects in an attempt to increase renal blood flow and protect the kidney from ischaemia.
NSAIDs block COX enzymes which leads to reduced prostaglandin synthesis, hence an insult which increases sympathetic stimulation is unopposed -> reduced renal blood flow -> ischaemia to the kidneys
Basic physiology for anaesthetists, Chambers, Huang and Matthews
Pharmacology for Anaesthesia and intensive care, Peck and Hill
Deranged Physiology – the links are within the article