Glomerular disease

Question 1

where does blood enter into the glomerulus and where does it go after

Answer 1

through the afferent arteriole - filtered across the glomerular membrane

Question 2

what proteins do not get filtered across the membrane

Answer 2

all proteins equal to or large than albumin (including immunoglobulin) will not be filtered - stay in plasma

Question 3

what comprises the filter barrier

Answer 3

it a membrane made up of three things (as plasma would be filtered)

1. endothelial cell cytoplasm
2. basal lamina (connective tissue)
3. podocytes (with interdigitating foot processes

Question 4

what are mesangial cells

Answer 4

tree-like groups of cells found inside the capillaries that support the capillaries

Question 5

after the glomerulus, where does filtrate go

Answer 5

the bowmans space and then into the proximal tubule

Question 6

what exits via the efferent arteriole

Answer 6

plasma containing blood cells, unfiltered proteins (e.g. albumin) and antibodies

Question 7

define glomerulonephritis

Answer 7

disease of the glomerulus - can be inflammatory or non-inflammatory

Question 8

what is the difference between primary and secondary GN

Answer 8

primary - only affects the glomerulus

secondary - affects other parts of the body too e.g. SLE or Wegeners)

Question 9

what is the aetiology of GN

Answer 9

some due to immunoglobulin deposition - immunoglobulin gets stuck in the filter (large sticky molecule)

some are diseases with NO immunoglobulin deposition (e.g. diabetic glomerular disease)

Question 10

what are the 4 common presentations of GN

Answer 10

1. Haematuria (blood in urine)
2. Heavy proteinuria* (nephrotic syndrome)
3. Slowly increasing proteinuria (can take years)
4. Acute renal failure (rapid rising creatinine)
   * usually albumin

Question 11

what are the main causes of haematuria

Answer 11

UTI
urinary tract stone
urinary tact tumour

Glomerulonephritis

Question 12

what is the most common cause of mesangial proliferative glomerulonephritis and how does this come about

Answer 12

IgA nephropathy
- IgA (and complement component C3) deposits in mesangium “irritate” mesangial cells and cause them to proliferate and produce more matrix

Question 13

what is the prognosis for IgA nephropathy

Answer 13

usually self limiting
BUT
small % go into chronic renal failure (via continued deposition of matrix - leads to sclerosis)

Question 14

CASE 1: 40 yr old man, discoloured urine (said to be straw coloured/translucent – now darker despite drinking enough fluid)

dipstick urine positive for blood BUT NOT proteins

urine culture normal

US abdomen normal

check clothing and renal biopsy - shows increased mesangium

differential diagnosis

Answer 14

mesangial proliferative GN

Question 15

what causes membranous glomerulonephritis

Answer 15

thickened glomerular basement membrane with spikes from deposition of IgG

spikes form when basal lamina matrix tried to surround and remove deposit

Question 16

why does the IgG get stuck in the basal lamina

Answer 16

deposits between basal lamina and podocyte but cannot go further along as it is too big - therefore initially not cleared and filtered into the urine - leads to build up

Question 17

what does IgI activate and what does this cause

Answer 17

activates complement (C3) which punches holed in the filter

Question 18

how would the usual complement (C3) cascade work

Answer 18

Complement – system in blood – like clotting cascade – function is to punch holes in bacteria – IgG binds to bacteria – cascade of complement goes on beside it

Good system for against bacteria – bad agaisnt own tissues

Question 19

what happens once C3 ha punched holes into the filter

Answer 19

leaky filter now allows albumin to filtered into urine - leads to nephrotic syndrome

Question 20

what is the underlying cause of IgG production and accumulation in membranous GN

Answer 20

unknown but sometimes have underlying malignancy

in many patients antigen is phospholipase A2 receptor - an antigen on podocytes

Question 21

how does diabetic nephropathy occur

Answer 21

long term diabetes leads to glycated molecules - deposited in matrix of basal lamina under endothelium and in mesangial matrix - thickened but leaky membranes +mesangial matrix compresses capillaries - reduced blood flow

also glomerulus adheres to bowmans capsule to try stop massive leakage of albumin into urine - causes podocytes to fall off

NO IMMUNE COMPLEXES

Question 22

what is formed when there is a build up of mesangial matrix due to glycation

Answer 22

nodules
= KIMMELSTEIL-WILSON LESIONS

**very characteristic of diabetic nephropathy

Question 23

what is the prognosis for diabetic nephropathy

Answer 23

inevitable decline if

1. established diabetic nephropathy
2. continued poor diabetic control

if changes made to lifestyle - won’t reverse state of glomerulus BUT will halt digression

Question 24

what are the 3 main causes of crescentic glomerulonephritis

Answer 24

1. granulomatotsis with polyangiitis (Wegeners granulomatosis)
2. microscopic polyarteritis
3. antiglomerular basement membrane

Question 25

what is granulomatosis with polyangiitis

Answer 25

a form of vasculitis (inflammation in vessels) that affects the vessels in the kidneys, nose and lungs

explains why patient may have a cough

Question 26

what would serum tests show for granulomatosis with polyangiitis

Answer 26

presence of anti-neutrophil cytoplasmic antibodies (ANCA)

Question 27

how does the presence of ANCA cause disease

Answer 27

NOT DEPOSITED IN KIDNEYS

Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils

antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells

Question 28

what is the treatment for granulomatosis with polyangiitis

Answer 28

can treat with chemotherapy - cyclophosphamide = 75% complete remission

BUT fatal if left untreated

Question 29

CASE:
Female, 50 years old
Unwell for 3 weeks
Cough

Serum biochemistry – creatinine 500 (was 60 one year before)

does this women have acute or chronic renal failure

Answer 29

acute as creatinine rapidly rising

Question 30

CASE:
Ultrasound: no renal tract lesion

Check clotting then renal biopsy - early endothelial damage with fibrin deposition
- huge bowmans space filled with cells (mostly macrophages) in a crescent shape

diagnosis =

Answer 30

crescent glomerulonephritis

Question 31

CASE: looking at her symptoms as well as renal biopsy result - what type of crescent glomerulonephritis does this lady have

Answer 31

cough = lungs affected

= granulomatosis with polyangiitis