Lecture 2 - Tubular Glomerular Feedback And Kidney Function

Question 1

What part of the kidney is the glomerulus found?

Answer 1

Cortex

Question 2

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?

Answer 2

20% of blood filtered

80% of blood exits via efferent artiole

Question 3

What forms the filtration barrier at the glomerulus/Bowmanns capsule?

Answer 3

Endothelial cells have gaps called fenestrations

Podocytes of basement membrane have negatively charged foot processes

Question 4

What are the 3 types of pressures which determine the filtration rate?

Answer 4

Hydrostatic pressure in the capillary/glomerulus

Hydrostatic pressure in Bowmanns capsule

Oncotic pressure in the glomerulus

Question 5

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?

Answer 5

Albumin

Question 6

What is the equation for net filtration using the hydrostatic pressures?

Answer 6

Net filtration = hydrostatic pressure in glomerulus - (hydrostatic pressure in Bowmanns + oncotic pressure in glomerulus)

Question 7

What 2 auto regulatory mechanisms ensure Renal Blood Flow and GFR remain constant?

Answer 7

Myogenic mechanism
Tubuloglomerular feedback

Question 8

What is the relative speed of the myyogenic mechanism and tubuloglomerular feedback mechanisms for regulating renal blood flow and GFR?

Answer 8

Myogenic mechanism = fast and autonomic

Tubulogllomerular = slower and uses multiple organs

Question 9

Why is it important that hydrostatic pressure in the glomerulus stays constant?

Answer 9

To ensure the nephron doesn’t get damaged

Question 10

How can a low blood pressure in the glomerulus cause Acute Tubular necrosis?

Which part of the nephron is likely to be affected?

Answer 10

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

Question 11

What is the Myogenic mechanism to counteract an Increased BP in the glomerulus?

Answer 11

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

Question 12

What is the Myogenic mechanism to counteract an Decreased BP in the glomerulus?

Answer 12

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

Question 13

What part of the nephron does the tubuloglomerular feedback system monitor/change?

Answer 13

DCT and the glomerulus

Question 14

On a basic level how does tubuloglomerular feedback change BP?

Answer 14

Macula densa cells detect levels of Na+ and Cl- and depending on levels affects vascular tone of afferent arteriole

Question 15

What is the overall function of Renin?

Answer 15

Increase blood pressure

Question 16

How does the Tubuloglomerular feedback work to reduce blood pressure if its too high in the glomerulus?

Answer 16

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

Question 17

How does the Tubuloglomerular feedback work to increase blood pressure if its too low in the glomerulus?

Answer 17

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

Question 18

What cells produce renin in the kidney?

Answer 18

Juxtaglomerular cells/granular cells

Question 19

What is the function of prostaglandins?

Answer 19

Vasodilator

Question 20

How does renin and the RAAS system work to increase blood pressure?

Answer 20

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

Question 21

What cells secrete prostaglandins when less Na+ reaches macula densa?

Then what cells are acted on?

Answer 21

Macula densa

Prostaglandins act on granular cells causing renin release

Question 22

How does the action of angiotensin II from the RAAS system increase BP?

Answer 22

Vasoconstriction efferent arteriole
Releases ADH
Stimulates thirst
Zona Glomerulosa releases aldosterone (increases Na+ reabsorption in DCT)

Question 23

What are the actions of prostaglandins?

Answer 23

Vasodilator preventing excessive vasoconstriction

Leads to renin release

Question 24

Why is creatinine clearance and GFR not the same thing?

Answer 24

Creatinine is partially secreted whereas substances used to measure GFR need to not be secreted

Question 25

What is the Myogenic response to maintaining GFR?

Answer 25

Contraction of blood vessels in response to increased blood pressure

Question 26

What happens to the afferent arteriole in response to increased pressure in arteriole?

Answer 26

Mechanoreceptors detect and vasoconstriction of afferent arteriole

Question 27

What is the tubuloglomerular feedback mechanism when theres an increased pressure in arteriole?

What detects this?

Answer 27

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

Question 28

What is the tubularglomerular feedback mechanism when arteriole pressure decreases?

What cells detect this?

Answer 28

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

Question 29

How does Renin production in the Tubularglomerular mechanism increase GFR/pressure?

Answer 29

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

Question 30

What prevents the over constriction of the afferent arteriole?

Answer 30

Prostaglandins

Question 31

Why does creatinine clearance overestimate GFR?

Answer 31

Its partially secreted so creatinine ends up in urine that isn’t actually filtered

Question 32

In a patient with advancing renal disease is the difference between creatinine clearance and true GFR greater or lesser?

Answer 32

Greater difference since patient with renal disease has a lower GFR so the difference is even larger