Glomerular disease pathology Flashcards
what does a normal glomerulus look like?
label glomerulus histology
how does blood enter the glomerulus?
via the afferent arteriole
where is blood filtered?
across glomerular membrane
All proteins equal to or larger than albumin (including immunoglobulins) will not be filtered - they will stay in plasma)
from the outside wht do podocytes have?
what are the three components of the filter barrier?
endothelial cell cytoplasm, basal lamina and podocyte
what are mesangial cells?
‘tree-like’ group of cells which support capillaries
where does filtrate from glomerulus go?
into Bowman’s space then into proximal tubule
what exists via efferent arteriole?
Blood cells, some fluid and albumin and larger proteins exit via efferent arteriole
Efferent arteriole (contains plasma, including unfiltered proteins such as albumin and antibodies)
wh
at is glomerulonephritis?
= Disease of glomerulus
Inflammatory or non-inflammatory
what is the aetiology of glomerulonephritis?
Some are due to immunoglobulin deposition
Some are diseases with no immunoglobulin deposition – for example - diabetic glomerular disease
what is glomerulonephritis?
Large range of conditions
Difficult to cover all variants
4 common presentations
1. Haematuria (blood in urine)
2. Heavy proteinuria (nephrotic syndrome)
3. Slowly increasing proteinuria
4. Acute renal failure
what are the three main causes of haematuria?
Urinary tract infection
Urinary tract stone
Urinary tract tumour
what is immonoflourecence done for?
Immunoglobulin (of IgA type) and complement component C3 in mesangial area of all glomeruli
IgA deposits (yellow arrow) cause increased proliferation of mesangial cells
Excess antibody (IgA) sometimes present in serum, but this is also true of some people who do not have IgA glomerulonephritis
Does IgA get filtered into urine?
No, the IgA is ‘stuck’ within the mesangium
what effect does IgA have on mesangial cells?
IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix
50 year old male
3 weeks of feeling unwell and swollen legs
Send of blood biochemistry and haematology tests 🡪 Serum albumin is low
what do you do if serum albumin is showed to be low?
Dipstick proteinuria
Send into hospital to see nephrologist
Nephrologist measures protein (albumin) in urine – very heavy loss
Clinical diagnosis of nephrotic syndrome – must be abnormality of glomerular filter
Check clotting screen then do renal biopsy:
why do you do clotting screen before renal biopsy?
risk of bleeding
what happens in membranous glomerulonephritis?
IgG is stuck in membrane
IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine
IgG is too big to be filtered into urine, but IgG activates complement (C3), which punches holes in filter
Leaky filter now allows albumin to be filtered into urine 🡪 nephrotic syndrome
Membranous glomerulonephritis - Prognosis
1/4 in chronic renal failure within 10 years
Underlying cause of IgG production and accumulation in membranous glomerulonephrits?
Unknown but can sometimes have underlying malignancy
In many patients antigen is phospholipase A2 receptor – why this protein? – as yet unknown.
Case 3
31 year old woman
Type 1 diabetes since 7 years of age
Long periods of poor glycaemic control
Developed retinopathy
Albumin in urine slowly increasing over last few years. Now has heavy protein leakage into urine
Check clotting screen then do renal biopsy
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)
diabetic nephropathy?
Female, 50 years old
Unwell for 3 weeks
Cough
Serum biochemistry – creatinine 500 (was 60 one year before)
Rapidly rising creatinine = acute renal failure
Ultrasound: no renal tract lesion
Check clotting then renal biopsy:
Crescentic glomerulonephritis Many causes of this pattern of injury, for example:A form of vasculitis (= inflammation in vessels) which affects vessels in kidneys, nose and lungs
causes of crescentic glomerulonephritis of injury?
Granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis)
Microscopic polyarteritis (a disease very much like granulomatosis with polyangiitis)
Antiglomerular basement membrane disease
Other - Many other forms of glomerulonephritis
wegners further tests?
Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA)
outdated name