Session 9 - Glomerular damage

Question 1

What are the main foci of kidney disease?

Answer 1

• Glomerulus
  
  • PCT
  • Interstitium
  • Vascular supply

Question 2

What is a primary glomerular injury?

Answer 2

• One which just effects the glomerulus

Question 3

What is a secondary glomerula injury?

Answer 3

• A systemic illness which happens to effect the glomerulus

Question 4

What are the four main sites of glomerular injury?

Answer 4

• Subepithelial 
		○ Anything that effects podocytes/podocyte side of glomerular basement membrane
	• Within glomerula basement membrane
	• Subendothelial 
		○ Inside the basement membrane
	• Mesangial/parameangial
		○ Supporting capillary loop

Question 5

Why can the nephron be termed a “functional unit”

Answer 5

• Same blood supply to glomerulus and nephron

○ Thus, ischaemic disease in glomerulus reduces blood supply to nephron, causing damage

Question 6

What are the two main pathologies of the glomerulus?

Answer 6

• It can become blocked 
		○ "Renal Failure"
		○ Decreased GFR
		○ Haematuria
	• It can leak 
		○ Proteinuria
		○ Haematuria
		○ One, other or both

Question 7

What is proteinuria?

Answer 7

• Presence of excess serum proteins in the urine (<3.5g filtered every 24 hours)

Question 8

What does proteinuria indicate?

Answer 8

• Podocyte damage, causing fenestration to widen and causing protein to be leaked when it would normally be filtered
Less severe nephrotic syndrome

Question 9

What is nephrotic syndrome?

Answer 9

• More than 3.5g of protein lost in urine per day

Soon becomes hypoalbuminaemia

Question 10

How does the body respond to hypoalbuminaemia as a result of nephrotic syndrome?

Answer 10

• Oedematous

* Liver starts to pump out more albumin, along with more cholesterol!

Question 11

What is nephritic syndrome?

Answer 11

• Glomerulus is blocked
  
  • GFR drops
  • Creatinine increases
  • Haematuria (glomerulus blood vessels ruptured)
  • Hypertensive

Question 12

What are the four main areas in the glomerula capillary loop where damage can occur?

Answer 12

• Subepithelial
  
  • With GBM
  • Subendothelial
  • Mesangial

Question 13

What is the difference between primary and secondary kidney disease?

Answer 13

• Primary kidney disease - Pathology soley affecting kidney

* Secondary kidney disease - Systemic disease which affects kidney

Question 14

What is the likely site of injury in proteinuria/nephrotic syndrome?

Answer 14

• Podocyte/subepithelial damage

Question 15

Give three primary causes of proteinuria/nephrotic syndrome

Answer 15

• Minimal change glomerulonephritis
  
  • Focal segmental glomerulosclerosis
  • Membranous glomerulonephritis

Question 16

Give two common secondary cuases of proteinuria/nephrotic syndrome

Answer 16

• Diabetes mellitus

* Amyloidosis

Question 17

When does minimal change glomerulnephritis occur?

Answer 17

• Occurs in childhood/adolescence

* Incidence reduces with increasing age

Question 18

What are the symptoms of glomerulonephritis?

Answer 18

• Heavy proteinuria or nephrotic syndrome
  
  • Responds to steroids
  • Usually no progression to renal failure

Question 19

Why does minimal change glomerulonephritis occur?

Answer 19

• Podocytes destroyed, loss of filtration slits

Question 20

What is the pathogenesis of minimal change glomerulonephritis?

Answer 20

• Unknown circulating factor damaging podocytes

* No immune complex deposition

Question 21

Why is minimal change glomerulonephritis called thus?

Answer 21

• Normal golmeurli under a light microscope

Question 22

How can you detect minimal change glomerulonephritis?

Answer 22

• Electron microscope, damage to podocytes evident

Question 23

What is Focal segmental glomerulosclerosis

Answer 23

• Nephrotic syndrome which effects adults

* Steroids minimally effective

Question 24

What does a patient with focal segmental glomerulosclerosis normal present with?

Answer 24

• Massive proteinuria
  
  • Haematuria
  • Hypertension
  • Renal failure

Question 25

Why is it called focal segmental glomerula sclerosis?

Answer 25

* Focal - Involving less than 50% of glomeruli on light microscopy * Segmental - Involving part of the glomerular tuft * Glomerular * Sclerosis - Scarring

Question 26

What is the main pathology of Focal segmental glomerulosclerosis?

Answer 26

* Damage to glomerulus causing scarring * Circulating factor damages podocytes * Progressive renal failure

Question 27

What causes Focal segmental glomerular nephritis?

Answer 27

• A circulating factor

Question 28

What is membranous glomerulonephritis?

Answer 28

Commonest cause of nephrotic syndrome in adults Immune complex deposits Capillary loop thick Basement membrane specley

Question 29

What causes membranous glomerulonephritis?

Answer 29

• Autoimmune response to podocytes • Immune complex deposits (IgG) ○ May also be secondary, as often associated with diseases such as lymphoma

Question 30

What is an immune complex?

Answer 30

* Äntigen complexed with multiple antibodies | * IgG destroy antigen found on podocytes, destroying podocytes in process

Question 31

What is a distinguishing feature of kidney disease as a result of diabetes mellitus?

Answer 31

• Progressive proteinuria Progressive renal failure

Question 32

How does the rule of thirds apply to membranous glomerulonephritis?

Answer 32

* 1/3 just get better * 1/3 grumble along, proteinuria but are fine * 1/3 progress to renal failure

Question 33

What is the pathology of kidney disease as a result of diabetes mellitus?

Answer 33

o Progressive proteinuria o Progressive renal failure o Microvascular (Damages glomerulus directly) o Mesangial sclerosis  nodules o Basement membrane thickening to 4-5x normal

Question 34

What is nephritic syndrome?

Answer 34

• Renal failure due to blocking of filter

Question 35

Give five causes of nephritic syndrome

Answer 35

* Good pasture syndrome * Vasculitis * IgA nephropathy * Thin GBM Nephropathy * Alport syndrome

Question 36

What is IgA nephropathy?

Answer 36

* Commonest glomerular nephropathy | * Characterised by deposition of IgA antibody in the glomerulus

Question 37

How does IgA present?

Answer 37

* Will present with haematuria when get cold, due to relationship with mucosal infections * Significant proportion progress to renal failure * Some, not all, patients have proteinuria

Question 38

What is haematuria as a result of IgA nephropathy a result of?

Answer 38

• Mesangial damage and scarring | - Significant proportion of patients progress to renal failure

Question 39

What happens to the mesangium in IgA nephropathy?

Answer 39

Mesangial proliferation and scarring

Question 40

Give two types of hereditatary nephropathy

Answer 40

* Thin GBM Nephropathy | * Alport syndrome

Question 41

Outline thin GBM nephropathy

Answer 41

Isolated Haematuria Thin GBM Benign Course

Question 42

What is alport?

Answer 42

* X linked * Abnormal collagen IV * Associated with deafness * Abnormal appearing GBM * Progresses to renal failure

Question 43

What is Goodpasture Syndrome?

Answer 43

* Rapidly progressive glomerular nephritis * Acute onset of severe nephritic syndrome * Classically associated with pulmonary haemorrhage

Question 44

What is the pathology behind goodpasture syndrome?

Answer 44

• Autoantibody to collagen IV in basement membranes Characterised by IgG deposition but no extracellular matrix deposit

Question 45

How is goodpasture syndrome treated?

Answer 45

* Treatable by immunosupression * Plasmaphoresis Take patients blood out, remove plasma with IgG in and then exchange plasma

Question 46

What is vasculitis?

Answer 46

* Inflammation of blood vessels which attacks highly vascularised kidney * No immune complex/antibody deposition * Blood vessels directly attacked by anti neutrophil cytoplasmic antibody * Nephritic presentation * Urgent biopsy required

Question 47

What is a subepithelial deposit?

Answer 47

• Antigen abnormally recognised on podocytes, circulating IgG binds to it, forming immune complexes in the glomerulus ○ Membranous glomerulonephritis

Question 48

What is a mesangial deposit?

Answer 48

• Immune complexes can be deposited directly in the mesangium as there is no podocytes or basement membrane to act as a barrier