Lecture 4 - Glomerular filtration

Question 1

What is filtered by the kidneys?

Answer 1

Plasma not blood

Question 2

What is the filtration barrier formed by anatomically?

Answer 2

1. ) fenestrated vascular endothelium
2. ) basement membrane
3. ) podocytes

Question 3

What are the podocytes separated by?

Answer 3

By slits in which they are called filtration slits because plasma is filtered between these slits. The slits are 25-60 nm wide and covered by a diaphragm.

Question 4

What is the filtration barrier formed by chemically?

Answer 4

Proteins like collagen, laminin and other extracellular matrix proteins such as the negatively charged heparin sulphate proteoglycans.

This provides a charge barrier and has a sieving function.

Question 5

What is the renal blood flow?

Answer 5

20 % of total cardiac output so 0.8-1 L/min

Question 6

What is the renal plasma flow rate ?

Answer 6

since RBC is 40 % of blood, it is about 0.5-0.6 L / min

Question 7

What is the glomerular filtration rate?

Answer 7

125 - 150 ml/min

Question 8

How much primary urine its produced in a normal adult per day?

Answer 8

140 L of primary urine (135-180 is normal).

Question 9

What is primary urine also called ?

Answer 9

Ultrafiltrate

Question 10

Maintenance of a…….. glomerular filtration rate (GFR) is one of the most important regulated parameters in the kidneys

Answer 10

constant

Question 11

what does glomerular ultra filtrate consist of?

Answer 11

water, small solutes, and normally protein free

Question 12

The regulated reabsorption of water and solutes allows for regulation of what?

Answer 12

• ECF volume
• osmolality
• acid-base balance
• homeostasis pf whole body phosphate, calcium, and potassium concentration

Question 13

What solutes are not fully reabsorbed or not absorbed at all?

Answer 13

urea, creatinine - freely filtered but not reabsorbed

Question 14

Why is more creatinine excreted than filtered ?

Answer 14

because of secretion. We secrete some so that makes the percentage that we excrete 130 %.

Question 15

The glomerular filtration barrier (GFB) is the most …… barrier in the body?

Answer 15

complex

Question 16

Why is the GFB the most complex barrier?

Answer 16

• high filtration rates of water
• nonrestricted passage of small and middle sized molecules
• almost total restriction of serum albumin and larger proteins
• despite all the workload it remains intact for 80 + years.

Question 17

Why are glomerular capillaries unique?

Answer 17

• because they have fenestrated area constituting of 20-50 % of the entire endothelial surface.
• It also facilitates high permeability.
• it is 60 nm in diameter whereas albumin only 3.6 nm hence endothelial cells do not determine the perm selectivity of the glomerular barrier.

Question 18

What is perm selectivity?

Answer 18

a measure of the ability of a membrane to discriminate between anions and cations.

Question 19

endothelial cell coat has ……..

Answer 19

charge selective properties

Question 20

What side of the blood vessels is covered by endothelial cell surface layer?

Answer 20

The luminal side of blood vessel walls

Question 21

What is endothelial cell surface layer comprised of?

Answer 21

negatively charged, glycolic proteins, glycosaminoglycans and membrane associated and secreted proteoglycans.

Question 22

What contributes to the perm selectivity of the glomerular wall?

Answer 22

the ESL most likely because init is rather thick and negatively charged.

Question 23

So what matters for a molecule that wants to pass through the membrane?

Answer 23

Size and charge

Question 24

What is the glomerular basement membrane comprised of?

Answer 24

• A fibrous network with a backbone of type IV collagen.
• mutations in the collagen chains has shown to give rise to severe pathological conditions (alports syndrome)
• proteoglycans such as agrin and perlecan
• glycoproteins which contribute to the selective properties of the barrier
• the charge density within the glomerular barrier is derived from a combination of the endothelial cell layer and GBM

Question 25

What are podocytes?

Answer 25

They are highly differentiated cells which line the outside of the glomerular capillaries and face the bowman’s space and primary urine.

Question 26

What is the diaphragm of the podocytes composed of?

Answer 26

nephrin - when mutated can cause massive leakage of protein and severe consequences for patients (congenital nephrotic syndrome)

Question 27

What is sieving (caused by the chemistry component of the basement membrane)?

Answer 27

• the basement membrane allows free passage for neutral molecules unto 6Kd MW (18 A radius). The negatively charged pores progressively restrict the passage of large (over 18 A) and almost completely sieve out neutral molecules that are larger than 40 A or smaller if negative (albumin).

In diseases, proteinuria may be because of loss of the negative charge selectivity or because of an increase in the number of large size pores.

Question 28

What is the filtrate composition?

Answer 28

• small MW neutral solutes (less than 6Kd) have concentrations equal to that in the plasma because they are freely filtered
• larger sized molecules especially negatively charged solutes are sieved partially or completely.
• Hb appears in urine with 68 Kd when there is intravascular hemolysis but albumin doesn’t also with 68 Kd. Because of charges

Question 29

What are the determinants of filtration?

Answer 29

movement of any molecule across the filtration membrane is measured by its flux.

Jv = k X S(change in P - oncotic pressure gradient)

Jv = Flux
k = Hydraulic conductivity
S = Surface area
P = Hydrostatic pressure gradient (gradient acting between the inside and outside of the capillary and bowman’s space)
Oncotic pressure gradient - oncoming pressure between eh inside and outside of the capillary and bowman’s space

Question 30

What are the factors that effect the glomerular filtration rate?

Answer 30

GFR - the amount of filtrate formed per unit time

Determinants:
- Kf (ultrafiltration coefficient) X Pu (net ultrafiltration pressure)

Look at notes too much shit