Lecture 2 - Tubular Glomerular Feedback And Kidney Function Flashcards
What part of the kidney is the glomerulus found?
Cortex
What percentage of blood from the renal artery gets filtered?
What percentage of blood arriving from the renal artery doesn’t get filtered and exits via the efferent arteriole?
20% of blood filtered
80% of blood exits via efferent artiole
What forms the filtration barrier at the glomerulus/Bowmanns capsule?
Endothelial cells have gaps called fenestrations
Podocytes of basement membrane have negatively charged foot processes
What are the 3 types of pressures which determine the filtration rate?
Hydrostatic pressure in the capillary/glomerulus
Hydrostatic pressure in Bowmanns capsule
Oncotic pressure in the glomerulus
What is the main plasma protein in the glomerulus that causes the oncotic pressure drawing water from the bowman’s capsule back into the glomerulus?
Albumin
What is the equation for net filtration using the hydrostatic pressures?
Net filtration = hydrostatic pressure in glomerulus - (hydrostatic pressure in Bowmanns + oncotic pressure in glomerulus)
What 2 auto regulatory mechanisms ensure Renal Blood Flow and GFR remain constant?
Myogenic mechanism
Tubuloglomerular feedback
What is the relative speed of the myyogenic mechanism and tubuloglomerular feedback mechanisms for regulating renal blood flow and GFR?
Myogenic mechanism = fast and autonomic
Tubulogllomerular = slower and uses multiple organs
Why is it important that hydrostatic pressure in the glomerulus stays constant?
To ensure the nephron doesn’t get damaged
How can a low blood pressure in the glomerulus cause Acute Tubular necrosis?
Which part of the nephron is likely to be affected?
If hydrostatic pressure low means less blood leaving efferent arteriole so less blood enters into the peritubular capillaries supplying the PCT and DCT and into the Vesa recta supplying the Loop of Henle
PCT where lots of reabsorption happens so very ATP sensitive
What is the Myogenic mechanism to counteract an Increased BP in the glomerulus?
Afferent arteriole constricts so less blood can get into glomerulus
Efferent arteriole vasodilates so more blood can flow out of the glomerulus
Reducing amount of blood in the glomerulus reducing GFR
What is the Myogenic mechanism to counteract an Decreased BP in the glomerulus?
Vasodilation of afferent arteriole more blood can flow into the glomerulus
Vasoconstriction of efferent arteriole so blood cant leave glomerulus as easily so more blood backs up in glomerulus
Increases GFR
What part of the nephron does the tubuloglomerular feedback system monitor/change?
DCT and the glomerulus
On a basic level how does tubuloglomerular feedback change BP?
Macula densa cells detect levels of Na+ and Cl- and depending on levels affects vascular tone of afferent arteriole
What is the overall function of Renin?
Increase blood pressure
How does the Tubuloglomerular feedback work to reduce blood pressure if its too high in the glomerulus?
GFR will be high if BP is high
Lots of Na+ and Cl- enter into macula densa cells (sodium potassium chloride transporters (NKCC))
Water follows the ions into the macula densa cells making them swell
Causing them to release ATP whic converted to adenosine which binds to A1 receptors on afferent arteriole leading to it’s vasoconstriction
Also renin production inhibited so RAAS activity reduced
How does the Tubuloglomerular feedback work to increase blood pressure if its too low in the glomerulus?
Macula densa cells contain less Na+ and Cl- since reduced GFR
Leads to them sending signals to juxtaglomerular cells causing them to release renin
Renin activates RAAS system to increase BP
Also prostaglandins released which stops constriction of afferent arteriole
What cells produce renin in the kidney?
Juxtaglomerular cells/granular cells
What is the function of prostaglandins?
Vasodilator
How does renin and the RAAS system work to increase blood pressure?
Renin converts Angiotensinogen to angiotensin 1
Angiotensin 1 converted to angiotensin 2 by ACE enzyme in lungs
Angiotensin 2 increases ADH production leading to more aquaporins being Translocated in collecting duct (more water reabsorbed)
Angiotensin II increases aldosterone production which increases expression of Na/K+ pump in nephron so more Na+ and therefore water reabsorbed
Angiotensin II causes vasoconstriction
What cells secrete prostaglandins when less Na+ reaches macula densa?
Then what cells are acted on?
Macula densa
Prostaglandins act on granular cells causing renin release
How does the action of angiotensin II from the RAAS system increase BP?
Vasoconstriction efferent arteriole
Releases ADH
Stimulates thirst
Zona Glomerulosa releases aldosterone (increases Na+ reabsorption in DCT)
What are the actions of prostaglandins?
Vasodilator preventing excessive vasoconstriction
Leads to renin release
Why is creatinine clearance and GFR not the same thing?
Creatinine is partially secreted whereas substances used to measure GFR need to not be secreted
What is the Myogenic response to maintaining GFR?
Contraction of blood vessels in response to increased blood pressure
What happens to the afferent arteriole in response to increased pressure in arteriole?
Mechanoreceptors detect and vasoconstriction of afferent arteriole
What is the tubuloglomerular feedback mechanism when theres an increased pressure in arteriole?
What detects this?
Macula densa cells detect it
Increased GFR means Macula Densa cells receive more Na+ and Cl-
Water follows these into cell making them swell
They release ATP which is converted to adenosine
Adenosine binds to A1 receptors in smooth muscle of afferent arteriole causing vasoconstriction
What is the tubularglomerular feedback mechanism when arteriole pressure decreases?
What cells detect this?
Less Na+ and Cl- in Macula Densa cells so cells swell less with water
Less ATP made so less Adenosine
Granular/juxtaglomerular cells make Renin activating the RAAS system
How does Renin production in the Tubularglomerular mechanism increase GFR/pressure?
Renin = rate limiting enzyme of RAAS
Leads to Angiotensin II production
Angiotensin II:
- adrenals make more aldosterone which inc Na+/K+ ATPase expression in collecting duct so more Na+ and water reabsorbed
-posterior pituitary makes more ADH so more aquaporins for water reabsorption
-more vasoconstriction from sympathetics making noradrenaline
What prevents the over constriction of the afferent arteriole?
Prostaglandins
Why does creatinine clearance overestimate GFR?
Its partially secreted so creatinine ends up in urine that isn’t actually filtered
In a patient with advancing renal disease is the difference between creatinine clearance and true GFR greater or lesser?
Greater difference since patient with renal disease has a lower GFR so the difference is even larger
