Glomerular disease pathophysiology

Question 1

Filtration unit

Answer 1

• basement membrane

- podocyte foot process -joined by tight junctions allow passage of molecules up to 4 nm

Question 2

Charge on capillary wall

Answer 2

Net negative charge because albumin

Question 3

Charge on podocytes

Answer 3

Negative charge -repels albumin

Question 4

Mesangial cells + role

Answer 4

Capillaries supported by mesangium jellow like substance, contractlie cell
Help regulate flow of blood through glomerular capillaries (fine changes in bp/flow)

Question 5

Size of capillary pore

Answer 5

4 nanometers

Question 6

What happens if glomeruli are injured - clinically?

Answer 6

1) Proteinuria
2) Hematuria
3) Decreased GFR

Question 7

Creatinine

Answer 7

Created by muscle metabolism. Filtered out of blood by glomeruli (none reabsorbed)

Question 8

Categories mechanisms of glomerular disease

Answer 8

1) Immune mechanisms
2) Hemodynamic
3) Podocyte injury
4) POlyanion loss
5) Metabolic/genetic

Question 9

Types of immune mechanisms

Answer 9

1) Antibody- mediated (IC, AGBM)

2) Cell-mediated

Question 10

Hemodynamic mechanism of glomerular disease

Answer 10

1) Hyperperfusion/hyperfiltration

2) Ischemic

Question 11

Types of metabolic/genetic

Answer 11

1) Familial

2) Acquired

Question 12

Immune complex mediated glomerular disease -origin of complexes (2)

Answer 12

• may be circulating and deposit in glomeruli

- may form in glomeruli

Question 13

How can identify immune complexes in the glomeruli

Answer 13

• fluorescence?? (around 20 min)

- get lumpy/bumpt

Question 14

How can identify immune complexes in glomeruli formed by circulating Ab complexes

Answer 14

• circulating antibodies stick to antigen in collagen IV

- when do direct immunofluorscence get linear/smooth stain outlining capillary walls of glomerulus

Question 15

Antibody-mediated mechanism??

Answer 15

1) Subendothelial/mesangial deposits
2) i) C’ activation -C5a
ii) Cell activation chemokines, adhesion
3) Both cause increase inflamatory cell migration to glomeruli (MO, PMN, T Cells)
4) Cytokines, procoagulan, growth factors, ROS proteolytic enzymes

Cytokines = leukocyte recruitment
Procoagulant = fibrin
Growth factors (PDGF, TGF)= cell proliferation increased EDC

Question 16

What happens if immune complexes form on epithelial side of basement membrane

Answer 16

1) Subepithelial deposits
2) C’ activation
3) MAC (C5-9)
4) Podocyte injury (get proteinuria but no proliferation so glomerulus look normal –> only through fluorescence can detect immune complexes)

Question 17

Hemodynamic moa of glomerula

Answer 17

• increased perfusion
• increased glomerular pressure
• glomeruli enlarged –> stretching leading to podocyte injury
• low perfusion through glomeruli
• glomeruli become ischemically contracted –> leading to podocyte injury

Question 18

Podocyte injury - mechanisms

Answer 18

1) mechanically injured
- i.e. stretch
2) by infection
- HIV
- Paro virus
3) Chemical injury
- drugs (clamitrin A –> for bones??)
4) Metabolic injury
- familial
- acquired

Question 19

MOA minimal change disease

Answer 19

-capillary charge lost

Question 20

Familial metabolic injury

Answer 20

• deficiency in enzyme responsible for metaablism of complex lipids –> build up in podocyte and cause injury
• another deficiency that leads to build up of cysteine

Question 21

Acquired metabolic injury

Answer 21

Complication high blood sugar in diabetes = glomerulo sclerosis

• get glycosylation of tissues that leads to advanced glycosylation end products
• have receptors in mesangial cells for these and stimulates meangial cell to reduce matrix + end products stick to structual proteins in glomerular basement membrane/proteins in mesangium and makes resistant to catabolism
• normally constant turnover of mesangium basement membrane - when glycosylation end product stick reduce catabolism= increase matrix and thickening of basement membranes