Met 2: Nephro; Lec. 4 Glomerular Filtration

Front 1

Describe the components of the filtration barrier

Back 1

3 parts to the filtration barrier 
- endothelial cells of the capillary
- basement membrabe
- epithelial cell podocytes/slit membrane

Front 2

Explain how the components of the filtration barrier determine the composition of the ultra filtrate

Back 2

Filtration is determined by
- the barrier across which material moves/pore size
- the forces that interact across the barrier

A) PORE SIZE
1) Endothetial cells of the capilary are fenestrated (lots of holes) with large pores (70-80nm) that allow most blood constituents to pass (except RBCs) note normal vascular endothelium is not fenestrated

2) Basement membrane is a net with a smaller pore size than the endothelium (4-8nm). Larger particles are impeded.

3) Slit membrane bridges gap between podocyte foot processes. Smaller pore size than basement membrane

B) FORCES ACROSS THE BARRIER
1) anion charge to the BM and slit membrane

Front 3

In the glomerulus,
a) neutral particles are filtered/not filtered based on?

b) anionic solutes cross more easily/less easily than cations

Back 3

a) For neutral particles size is the discriminator - ie less than 10,000MW cross

b) because the barrier has a (-) charge, anionic solutes cross less easily than cations
**albumin --> based on size should cross but based on charge is prevented from entering filtrate

Molecules that cross easily
- sodium, potassium, cholide, water, urea, glucose, sucrose, polyethylene glycol
- inulin, lysozyme and myoglobin cross OK

Molecules that do not cross
- albumin, hemoglobin

Front 4

What are starling forces responsible for glomerular filtration?

Back 4

Starling forces: hydrostatic and oncotic forces that determine the movement of fluid across capillary membranes

Hydrostatic forces: exerted by fluid at equilibrium due to force of gravity

Oncotic forces: osmotic pressure exerted by proteins in blood vessel

Oncotic and hydrostatic forces are in opposition 

In the glomerulus
a) Forces that promote filtration
- high hydrostatic force 
- high MW solutes in boman's space have smaller oncotic effect - this force should be 0 as these high MW solutes should not pass through an intact barrier
*thus hydrostatic is the only starling force to promote filtration

b) Forces that prevent/impede filtration
- back pressure from filtrate (10-15mm small but significant)
- oncotic pressure within the capillary

NET pressure drives filtration - is roughly 15mmHg

Front 5

T/F - filtration pressure is equal across the capillary

Back 5

F
- highest at the proximal part of the capillary
- increasing concentration of albumin in the plasma along the length increases the oposing oncotic pressure to filtration

Front 6

Asuming Starling forces remain the same, does increased renal plama flow increase/decrease GRF

Back 6

- Increased renal flow increases the GFR --> increased NET ultafiltration pressure 
- linear relationship to 100% of normal then plateaus

Front 7

How does the afferent and efferent arteriolar resistance affect renal blood flow and GFR?

Back 7

the afferent arteriole resistance is modified to maintain consistent renal flow and filtration in the face of fluctuating BP
- this process is mediated by autoregulation

Front 8

What is the macula densa

Back 8

The region of the DCT that comes in contact with the afferent arteriole

Front 9

What is autoregulation of the renal blood flow and GFR

Back 9

Autoregulation of the afferent arteriolar resistance allows maintenance for renal blood flow and GFR

Two mechanisms accomplish this:
1) myogenic response of afferent arterioles
2) Tubularglomerular Feedback

Front 10

Explain the myogenic hypothesis of auto regulation

Back 10

1) Increase in BP stretched the smooth muscles of the afferent arteriolar wall
2) stretch sensitive Ca2+ channels are opened, leading to Ca2+ influx and contraction
3) this vasoconstriction minimizes the increase in hydrostatic pressure in the glomerular capsule

* decrease in BP reduces tonic level of arteriolar smooth muscle contraction --> vasodilation will sustain the hydrostatic glomerular capsule pressure

Front 11

Explain the process of tuberuloglomerular feedback and autoregulation of RBF and GFR

Back 11

- this process is unique to the kidney
- regulation of flow at the level of each nephron by each nephron
--> illustrates how important BP regulation is for the kidney

1) Macula densa region of the distal tubule has sensory cells that monitor [Na+] and [Cl-] in the afferent arteriole
2) Senses increase in delivery of Na+ or Cl- in the afferent arteriole. Increases [Na+]/[Cl-] is implied to be due to an increase in GFR and thus pressure
3) triggers release of vasoconstrictors (adenosine and ATP) from the macula densa. Vasoconstriction of the afferent arteriole reduces glomerular pressure 

**lower Na+/Cl- delivery triggers the release of vasodilators to the afferent arteriole (NO and PG)

**Note these are paracrine signals

Front 12

What happens to GFR when there is an increase in circulating vasoconstrictors/vasodilators?

Back 12

- increase in circulating vasoconstrictors
- autoregulation is over-ridden thus starling forces are altered in the kidney
- kidney responds to the circulating vasoconstrictors (NE, Angiotensin II) 
- note still mostly target the afferent arteriole, however Angiotensin II targets efferent arteriole (high doses target the afferent arteriole)

- kidney will also respond to vasodilators only in the afferent arteriole

Front 13

"Constriction of the afferent arteriole 
- increases/decreases GFR, renal plasma flow, pressure in the glomerulus?

Constriction of the efferent arteriole
- increases/decreases GFR, RPF, Pgc?"

Back 13

"Afferent arteriole constriction decreases GFR, Pgc and RPF

Efferent arteriole constriction increased Pgc, decreases RPF and increases/decreases GFR depening on Pgc and RPF

This is because renal blood flow modifies GFR indepndently of the starling forces. Constriction/dilaion of the afferent changes pressure and flow in tandem. Efferenct constriction increases pressure and reduces flow. Which force predominates determines increase/decrease in GFR in the face of efferent arteriole constriction/dilation. At higher pressures the reduction in flow has a greater impact on GFR and it drops. "

Front 14

What is renal clearance?

Back 14

- substances that appear in the urine must have been filtered by the kidney. Using the clearance of certain substances we can estimate the GFR

Front 15

Limitation of creatinine for estimation of GFR

Back 15

"- it is good because it is made by the body in catabolism and muscle breakdown, it is freely filtered and not reabsorbed
- some amount is secreted however so it OVERESTIMATES GFR"