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Flashcards in Glomerular Disease Deck (32):
1

What proteins will not be filtered across the glomerular membrane?

All proteins equal to or larger than albumin (including immunoglobulins)

2

What are podocytes?

Cells in the Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus.

The long processes, or foot projections (pedicels) of the podocytes wrap around the capillaries, and leave slits between them. Blood is filtered through these slits, each known as a filtration slit or slit diaphragm. Several proteins are required for the foot projections to wrap around the capillaries and function.

3

What is nephrin?

Nephrin is a zipper-like protein that forms the slit diaphragm, with spaces between the teeth of the zipper, big enough to allow sugar and water through, but too small to allow proteins through.

4

What 3 things make up the Glomerular membrane/ filter barrier?

Endothelial cell cytoplasm,
Basal lamina,
Podocyte

Sort of 3 layer sandwich of endothelium then basal lamina (connective tissue) and then projecting podocytes

5

What are mesangial cells?

"Tree like" group of cells which support capillaries

Specialized cells around blood vessels in the kidneys, at the mesangium. Primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris.

The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.

6

What is glomerular nephritis?

Disease of glomerulus
-May be inflammatory or non-inflammatory

7

What is the difference between primary and secondary glomerular nephritis?

Primary (only affects glomerulus)

Secondary (other parts of body affected e.g. SLE or Wegener's)

8

What is the aetiology of glomerulonephritis?

Some are due to immunoglobulin deposition

Some are diseases woth NO immunoglobulin deposition (e.g. diabetic glomerular disease)

9

What does glomerulonephritis cover?

Large range of conditions

Difficult to cover all variants

10

What are the 4 common presentations of glomerulonephritis?

1. Haematuria (blood in urine)

2. Heavy proteinuria (nephrotic syndrome)

3. Slowly increasing proteinuria

4. Acute renal failure

11

What are the main causes of haematuria?

Urinary tract infection

Urinary tract stone

Urinary tract tumour

Glomerulonephritis

12

What tests could you carry out in haematuria?

Send of urine culture
Abdomen USS

If both negative -> Check clotting then proceed to renal biopsy

13

What is IgA glomerulonephritis?

IgA deposits in mesangium
-Get stuck are not cleared
-No presence of IgA in urine

Increased proliferation of mesangial cells -> to try clear
-Mesangial cells try to produce more matrix


Aetiology unknown
Unknown how haematuria is caused

14

What is the prognosis of IgA nephropathy?

Usually self-limiting
-i.e. return to normal

Small % go onto chronic renal failure (via continued deposition of matrix)

15

What may be a renal cause of hypoalbuminaemia?

Nephrotic syndrome
-Abnormality of glomerular filter

Lots of albumin lost to urine

16

What is the appearance of membranous glomerulonephritis?

Thickened glomerular basement membrane.

Spikes of new basement membrane matrix material underneath podocytes

Deposit of IgG between basal lamina and podocyte

Basal lamina spike created (matrix which tries to suround and remove the deposit)

This all creates a thickened membrane

17

What is the pathology of membranous glomerulonephritis?

Deposit of IgG between basal lamina and podocyte but cannot go further and is not filtered into membrane.

IgG activates complement (C3), which punches holes in filter

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

Glomerular membrane is thickened but leaky, allowing albumin through

18

What is the prognosis of membranous glomerulonephritis?

1/4 in chronic renal failure within 10 years

19

What is the underlying cause of IgG production and accumulation in membranous glomerulonephritis?

Unknown but can sometimes have underlying malignancy

In many patients antigen is phospholipase A2 receptor (not known why)

20

What is a good investigative approach to hypoalbuminaemia for renal disease?

Clotting screen

Renal biopsy

21

Give a description of a Diabetic glomerulus?

Glycated molecules -> Matrix deposition in basal lamina underlying endothelium and in mesangial matrix

-> Thickened but leaky basement membranes + mesangial matrix compresses capillaries (NO immune complexes)

22

Describe diabetic nephropathy

Thickened capillary wall which is leaking albumin

Increased mesangial matrix which compresses capillaries (glycated depositions)

Small compressed capillary lumen

Thickened, narrowed arterioles reduce blood flow to glomerulus

Adhesions to Bowman's capsule are glomerulus' attempt to stop massive leakage of albumin into urine

23

What are Kimmelsteil-Wilson lesions?

Nodules of mesangial matrix found in diabetic nephropathy

Gross excess of mesangial matrix forming nodules

24

What is the prognosis of diabetic nephropathy?

Inevitable decline if:

1. Established diabetic nephropathy and if

2. Continued poor diabetic control

25

What does a rapidly rising creatinine show?

Serum biochemistry showing rapidly rising creatinine = acute renal failure

26

Describe the appearance of Crescentic glomerulonephritis

Early endothelial damage with fibrin deposition

Cellular proliferation and influx of macrophages (= crescent) around glomerular tuft, within bowman's capsule

(Crushed glomerulus "tuft" currounded by a crescent of macrophages)

27

There are many causes of the pattern of injury seen in Crescentic glomerulonephritis.

Give some causes

WEGENER'S GRANULOMATOSIS

Microscopic polyarteritis (disease very much like Wegener's)

Antiglomerular basement membrane disease

Many other forms of glomerulonephritis

28

What is Wegener's granulomatosis?

A form of vasculitis (= inflammations in vessels) which affects vessels in kidney's nose and lungs

29

What tests can you do for Wegener's?

Serum test shows presence of anti-Neutriphil cytoplasmic antibodies (ANCA)

30

What are Anti-neutrophil cytoplasmic antibodies (ANCA)?

NOT deposited in kidney

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

31

How does ANCA produce tissue damage?

Via interactions with primed neutrophils and endothelial cells

32

What is the prognosis of Wegeners?

Fatal (mean survival 6 months) if left untreated

Cyclophosphamide - 75% complete remission