Glomerular Filtration Rate

Question 1

Describe the nature of the glomerular filtration barrier.

Answer 1

1. Filtration membrane:
   - Fenestrated endothelium (pores on inner side)
   - Basement membrane
   - Filtration slits (between podocytes foot processes - on outer side of glomerular tube)
2. Glycocalyx –> proteoglycans on lumen surface of endothelial cells –>
   negatively charged –> repels large negatively charged proteins.
3. Fenestrae –> opening between the endothelial cells –> allow water and small molecules to pass –> increases the permeability of glomerulus
4. The glomerular basement membrane –> collagen, laminin, fibronectin and proteoglycans –> barrier to glomerular filtration –> negatively charged –> also repels large negatively charged
5. Inner surface of Bowman’s capsule is lined by podocytes –> foot processes which interdigitate with one another to form filtration slits.
6. The podocytes and its foot processes are covered by negatively charged proteoglycans as well.

Question 2

Mesangial cells

Answer 2

Specialized cell –> part of renal corpuscle.

Functions: remove macromolecules, contraction to change blood flow, support the mesangial matrix,
phagocytose immunoglobulins trapped in the basal lamina of glomerulus.

Clinical significance: diabetic nephropathy

AT II binding to receptor stimulates mesangial cell contraction

Question 3

Normal eGFR

Answer 3

> 90ml/min/1.73m^2

is normal

Question 4

Creatinine

Answer 4

40-90 micromole/L

Question 5

Describe the Starling forces involved in the formation of the glomerular ultrafiltrate and

Answer 5

Four Starling forces:

PGC: HSP in glomerulus.
πGC: OP in glomerulus.
PBS: HSP in Bowman’s capsule.
πBS: OP in Bowman’s capsule=0 normally.

HSP –> pro filtration
OP –> antifiltration. (-ve sign)

Question 6

Describe how the Starling forces along a glomerular capillary differ from those in an extra-renal capillary.

Answer 6

Most capillaries in body have constant OP , and changing HSP. usually higher in artery = filtration and lower in venous side = absorption.

HOWEVER in Glomerular capillaries, HSP of capillary is constant, while COP changes slightly => there is net filtration along entire length of glomerular capillaries.

Question 7

Glomerular filtrate

Answer 7

The glomerular filtrate has the same characteristic as the plasma:

1. 280 – 290 mOsm/kg H2O
2. pH = 7.35 – 7.45
3. Solute composition
4. BUT, negligible/no proteins, no cells!!!

Filtered load is the amount of a substance filtered into the Bowman’s capsule per unit time.

Filtered load = GFR x plasma concentration

Question 8

Glomerular filtration rate

Answer 8

GFR is the rate at which glomerular filtrate is produced.

It is affected by the Starling forces and the ultrafiltration coefficient of glomerulus which form the Starling equation.

Kf –> depend on total surface area and permeability of the glomerulus

High Kf –> high permeability –> favors GFR

Question 9

Starling equation

GFR =

Answer 9

GFR = Kf [ (PGC – PBS ) – (πGC – πBS)

GFR is affected by the starling forces and the ultrafiltration coefficient.

Kf is proportional to total surface area and glomerulus permeability

Question 10

Normal kidney morphology and structural changes in diabetes mellitus

Answer 10

Diabetic kidney disease induces structural changes including thickening of the glomerular basement membrane, fusion of foot processes, loss of podocytes with denuding of the glomerular basement membrane and mesangial matrix expansion

Question 11

Long standing hyperglycemia –>

Answer 11

MESAc glucose consumption

MESAc expansion and cellular hypertrophy

Increase in GFR

If untreated, TGF beta is released which stimulates fibrosis

Glucose binds irreversibly to proteins formed AGE

AGE’s can form complex of crosslinks over years of uncontrolled hyperglycemia and might possibly contribute to renal damage

Question 12

Describe the importance of autoregulation of both renal blood and glomerular filtration rate

Answer 12

Mechanisms of renal autoregulation:

1. myogenic
2. tubuloglomerular

Question 13

Describe the importance of circumstances under which glomerular filtration rate changes independently of renal blood flow.(what can cause changes in Kf)

Answer 13

Circumstances under which glomerular filtration rate changes independently of RBF :

1. Diabetic Nephropathy - constricted EA
2. NephrItic syndrome = inflammation of the glomerulus –> increases the permeability of filtration membrane –> hematouria, proteinuria, hypertension
3. NephrOtic syndrome = inflammation can be one of the causes –> increases in permeability –> proteinuria, hypoalbuminemia, edema

Question 14

Describe how changes in vascular resistances and renal plasma flow influence glomerular filtration.

Answer 14

Vascular resistance influence RPF and therefore GFR.

eg.

AA constriction  less blood flow  decrease PGC  decrease GFR (AA resistance increase)

EA constriction  less blood leaving glomerulus  blood pools in glomerulus  increase PGC  increase GFR (EA resistance increase)

AA dilation  more blood flow  increase PGC  increase GFR (AA resistance decrease)

EA dilation  more blood leaving glomerulus  less blood in glomerulus  decrease PGC  decrease GFR (EA resistance decrease)

Question 15

Glomerular filtration – size and charge matter

Answer 15

Dextrans are polysacharrides that can be synthesized as neutral, negatively or positively charged molecules. Also, it can be synthesized in different molecular weight.

smaller and positively charged molecules are best filtered by the glomerulus.

Question 16

Describe the amount of fluid and solutes filtered and reabsorbed by the kidney per day.

At the proximal convoluted tubule…

Answer 16

% of filtered load of solutes reabsorbed:

sodium and water = 66
glucose and aa = 100
potasssium = 65
urea = 50
phosphate = 80

Question 17

Glomerulo-tubular balance (distinguished this from tubuloglomerular feedback) ensures that ______________

Answer 17

whenever GFR increases (which increases the filtered load), a constant amount of the filtered substance is reabsorbed (for example, 66% of the filtered sodium will be reabsorbed at the proximal tubule regardless of the GFR).

Question 18

Describe the methods used to estimate and measure glomerular filtration rate and renal plasma flow and their limitations.

Answer 18

Measuring GFR:

• Freely filtered (small, uncharged, not bound to plasma protein)
• Not reabsorbed nor secreted
• Not synthesized nor metabolized
• Not toxic so that it does not affect renal function

= INULIN or CREATININE

Question 19

Renal handling of inulin

Answer 19

Filtered load = excreted load.

𝐹𝑖𝑙𝑡𝑒𝑟𝑒𝑑 𝑙𝑜𝑎𝑑=𝐺𝐹𝑅 ×𝑝𝑙𝑎𝑠𝑚𝑎 [𝑖𝑛𝑢𝑙𝑖𝑛]

𝐸𝑥𝑐𝑟𝑒𝑡𝑒𝑑 𝑙𝑜𝑎𝑑=𝑈𝐹𝑅 ×𝑢𝑟𝑖𝑛𝑒 [𝑖𝑛𝑢𝑙𝑖𝑛]

𝐺𝐹𝑅= (𝑈𝐹𝑅 ×𝑢𝑟𝑖𝑛𝑒 [𝑖𝑛𝑢𝑙𝑖𝑛])/(𝑝𝑙𝑎𝑠𝑚𝑎 [𝑖𝑛𝑢𝑙𝑖𝑛])

𝐺𝐹𝑅=𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓 𝑖𝑛𝑢𝑙𝑖𝑛

But, inulin is rarely used for this purpose because it requires infusion.
Instead, creatinine is used.

Question 20

Renal handling of creatinine

Answer 20

𝐹𝑖𝑙𝑡𝑒𝑟𝑒𝑑 𝑙𝑜𝑎𝑑=𝐺𝐹𝑅 ×𝑝𝑙𝑎𝑠𝑚𝑎 [𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒]

𝐸𝑥𝑐𝑟𝑒𝑡𝑒𝑑 𝑙𝑜𝑎𝑑=𝑈𝐹𝑅 ×𝑢𝑟𝑖𝑛𝑒 [𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒]

𝐺𝐹𝑅= (𝑈𝐹𝑅 ×𝑢𝑟𝑖𝑛𝑒 [𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒])/(𝑝𝑙𝑎𝑠𝑚𝑎 [𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒])

𝐺𝐹𝑅=𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒

Creatinine is a by-product of muscle metabolism. It is freely filtered by the glomerulus. Therefore, its concentration in the glomerular filtrate is the same as its plasma concentration.
Creatinine is SECRETED which over-estimate GFR by 10%. But, the quatification method of plasma creatinine under-estimate GFR by 10%.
As both off-set each other, creatinine clearance is a good surrogate for measuring GFR when GFR is normal.