Lecture 2 - The Glomerulus

Question 1

How much fluid is filtered through the glomerulus per day?

How much of that fluid actually excreted as urine?

Answer 1

• 180L (roughly)

- Just 1.5L, therefore mostly everything reabsorbed

Question 2

Give a brief recap of the body fluid compartment numbers in an average 70kg male
Which body fluid compartment does the kidney directly regulate?
What is the electrolyte composition of ICF + ECF?

Answer 2

• Kidney directly regulates ECF
• ICF = High K+, Low Na+
• ECF = Low K+, High Na+ (due to action of Na/K ATPase)

Question 3

Define:

Osmolality

Osmolarity

Answer 3

Osmolality = solute per Kg of solvent
Osmolarity = number of osmoles of solute per litre 

Measured in mOsm

Question 4

Define + Give typical values for:

Renal blood flow (RBF)
Renal plasma flow (RPF)
Glomerular filtration rate (GFR)
Filtration Fraction (FF)

Answer 4

1) . RBF = flow of blood through renal arteries reaching the kidneys, around 1L/min.
2) RPF = flow of plasma part of blood into kidneys (RBF x 1-HCT). HCT is usually 40% so typically 600mL/min.
3) GFR = amount filtered out of the glomerulus, typically 125 mL/min
4) FF = GFR/RPF, typically 20%

Question 5

What is the resulting fluid that has been filtered out of the glomerulus called?
What does this fluid contain + not contain?

Answer 5

• Ultra-filtrate
• No blood cells or platelets
• No proteins
• Organic solutes w/low MW and inorganic ions

End product of filtration is identical to plasma without large proteins and cells

Question 6

Describe how the structure of the glomerular capillary membrane provides selective permeability for what can be filtered out into Bowman’s space?

Answer 6

• Fenestrations between endothelial cells are small to only allow small molecules to pass, RBC’s & large proteins will not fit
• Foot processes (podocytes) form mesh around basement membrane which again prevent large molecules from passing
• Negatively charged, therefore repels proteins and RBC’s (electrochemical barrier)

Anything above MW of 5200 or molecular radius of 1.48nm is too large to be filtered. In many diseases negative charge barrier is lost or fenestrations are widened, leading to proteinuria.

Question 7

What are the 3 different pressures (Starling forces) that are balanced to provide a net filtration pressure for substances to pass through the glomerulus into Bowman’s space?

What is the number in mmHg of this net filtration pressure?

Answer 7

1) Hydrostatic pressure in the capillary/Pgc (largest) - 50mmHg
2) Hydrostatic pressure in bowmans capsule/Pbc (smallest) - 12mmHg
3) Oncotic pressure difference between capillary & tubular lumen/piGC - 25mmHg

Overall result is net filtration pressure allowing for filtration of substances through the glomerulus.

Pgc - (Pbs + Pibs) = 50 - (12+25) = 13mmHg

Question 8

RBF + GFR remain relatively constant because of autoregulation. What are the two main mechanisms involved in autoregulation?

Answer 8

1) Myogenic Mechanism

2) Tubuloglomerular Feedback

Question 9

Describe where & how the myogenic mechanism of autoregulation maintains RBF + GFR is they get too high or too low.

Answer 9

• Arterial SM responds to increases & decreases in vascular wall tension, predominantly occurs in preglomerular resistance vessels (arcuate, interlobular and predominantly afferent arterioles). Occurs rapidly (3-10s).
• To decrease GFR = 1) constrict afferent arteriole to reduce blood entering glomerulus OR 2) dilate efferent arteriole to increase blood leaving glomerulus. This is in response to high BP.
• To increase GFR = 1) dilate afferent arteriole to increase blood entering glomerulus OR 2) constrict efferent arteriole to reduce blood leaving glomerulus. This is in response to low BP.

Question 10

Describe how tubuloglomerular feedback responds to high BP/high tubular flow and reduced GFR

Answer 10

• Macula densa cells of DCT epithelium detect osmolality/rate of Na+/Cl= movement into cells. The higher the rate of flow, the higher the Na+ conc in cells (as they have NaK2Cl transporters)
• Signal sent to juxtaglomerular cells, leads to release of ATP, converted to adenosine, binds with A1 receptor on afferent arteriole.
• Causes constriction of SM on adjacent afferent arterioles, reducing RPF which reduced GFR. Also inhibits renin synthesis.

Question 11

Describe how tubuloglomerular feedback responds to low BP in order to increase GFR

Answer 11

• Low BP = low GFR. This means waste products can build up in blood
• Renin released by JG cells in response to 1) sympathetic nerve stimulation 2) decreased stretch of afferent arteriole 3) signals from macula densa cells after decreased NaCl delivery
• Angiotensinogen –> Ag1 (via renin) –> Agll (via ACE) –> constricts efferent arterioles –> increases GFR.

ALSO - get release of prostaglandins which reduce constriction of afferent arteriole