Glomerular Pathology Flashcards
What are the renal cortical compartments where different pathologies can occur
Glomerular, tubular, interstitial, vascular
Describe how pathology. Of one part of the nephron can affect others
Blood supply of nephron is derived from glomerulus itself. Damage to the glomerulus means blood wont full though it - reduce gfr - less blood to nephron - nephron becomes ischaemic, then nephron function reduced.
Describe how the filter can block or leak
• Filter can block “Renal Failure” – reduced eGFR — increased creatinine Nephritic syndrome - Hypertension, blood in urine, ?????
• Filter can leak – Proteinuria - albumin – Haematuria – One, other or both NEphrotic syndrome: 3.5g/ 24h - proteinuria. Hypoalbuminaemia. Oncotic pressure drops. Generalised oedema. Fluid cant be pulled bac. High co=holesterol - peeing out LDLs. Losing proteins that stop clotting. Lose igG - immunocompromised
Describe how the site of glomerular injury determines clinical presentation
Leaking protein - selective permeability has been affected - that must mean the membrane has been effected. Any of the components can be affected. Either with podocytes or basement membrane. Losing too much protein.
If glom is blocked. Blood not getting through a vessel - something wrong with vessel or endothelium. Clotting, swelling, inflammatory cells marinate, blood cant get through..
if something affects mesangium - inbwteen picture - can then affect a lot of other structures
How can immune complex deposition cause kidney damage
Iabnormally circulating antibody - filtered in kidney - damage kidney by activating complement - cause injury, inflammation, renal damage Immune complex deposition (antigen- antibody)/circulating factors
What are teh sites and common causes of nephrotic syndrome
Proteinuria/Nephrotic Syndrome
• Likely Site of Injury?
– Podocyte/subepithelial damage
• Common primary causes
– Minimal Change Glomerulonephritis
– Focal Segmental Glomerulosclerosis (FSGS) - (affects some glomerulus, affects some parts of these glomeruli)
– Membranous Glomerulonephritis
• Common secondary causes
– Diabetes Mellitus
– (Amyloidosis)
Describe teh presentation fo minimal change glomerulonephritis
- Childhood/Adolescence, generally 16-20
- Incidence reduces with increasing age
- Heavy proteinuria or nephrotic syndrome - swelling at ankles, frothy urine (lot of protein in it)
- Responds to steroids (give it in turnover time of podocytes)
- May recur - if you stop steroids it may come back. Patients on and off steroids until it wanes with age
- Usually no progression to renal failure
Describe the change to glomerulus and pathogeneis of minimal change glomerulonephriris
Glomerulus looks normal but losing a lot of protein, using silver stain, basement membrane looks normal. On electron microscopy - podocytes have been lost - acutely damaged - lots of protein freely moved across.
• Unknown circulating factor damaging
podocytes
• No immune complex deposition
Describe the presentation of fsgs
Similar to minimal change
• Nephrotic
• Adults eg in 40s
• Less responsive to steroids bc started to scar
• Glomerulosclerosis
• Circulating factor damaging podocytes (transplants) - they scar, glomerulus does not stay normal so…
• Progressive to renal failure as GFR is reducing, potentially renal transplant
— if transplanted - the new kidney can start leaking protein almost instantaneously, which suggests it is a circulating factor
Describe the presentation of membranous GN
- Commonest cause of nephrotic syndrome in adults
- Rule of thirds 1/3 get better 1/3 stay same, 1/3 go downhill
- Immune complex deposits (antibody/antigen) - deposited in kidney, damage podocytes
- Probably autoimmune - PLA2-R
- May be secondary (associated with other pathologies e.g. lymphoma)
Describ the histology in membranous
Ss
Describe the pathogeneses of subepithelil deposits
Complexes wont get through to sub epithelial compartment. Stopped by endothelial cells. Cant get to podocytes. Unless filtering system damaged. Suggested there is an antigen of podocytes. Body produced igG in response to this (autoimmune), or antigen filtered into glom and body makes antigen against it. IgG stuck - made the complex there. Phospholipase a2 receptor sits on podocytes.
Sir the test for circulating igG. Biopsies as well.
Desribe DM as a secondary cause of renal failure
- Progressive proteinuria - protein/creatinine ratio - estimation of 24 hour loss.
- Progressive renal failure - progress towards renal failure as kidneys start to scar
- Microvascular - small blood vessels it glomerulus
- Mesangial sclerosis -> nodules
- Basement membrane thickening - excess glucose becomes glycosylated - causes them to thicken.
Describe haematuria
• Haematuria – Site of Injury? – IgA Nephropathy – Thin glomerular basement membrane disease (too thin leak blood)/Hereditary Nephropathy (Alport)
Describe nephrotic syndrome
• Nephritic Syndrome
– Site of Injury? – Goodpasture Syndrome
– Vasculitis
What is IgA neuropathy
- Commonest GN
- Any age
- Classically present with visible/invisible haematuria - activated igA
- Relationship with mucosal infections • Variable histological features & course
- +/- proteinuria
- Significant proportion progress to renal failure
- No effective treatment
Explain the pathogenesis of iga nephropathy
Deposition of circulating IgA containing immune complexes
IgA deposited in mesangium, looks abnormal. Too many cells or too mcuh matrix
Immune complex has direct acces to mesangium - causes mesangium damage - haematuria, proteinuria, renal failure as it becomes more damaged
Desribe the spectrum of hereditary nephropathies
- Thin GBM Nephropathy • Benign Familial Nephropathy
- Isolated haematuria
- Thin GBM
- Benign course
• Alport • X linked • Abnormal collagen IV • Associated with deafness • Abnormal appearing GBM • Progresses to renal failure
What is goodpasure syndrome
Anti gbm antibody, usually to collagen 4. Destroys glomerulus quickly
• Relatively uncommon though clinically important - need to be treated quickly
• Rapidly progressive GN (on call service for these matinees - need to be diagnosed in 24 hours)
• Acute onset of severe nephritic syndrome - hypertensive, significant renal failure, reported blood in urine
• Classically described association with pulmonary haemorrhage (smokers) - coughing up blood
• Autoantibody to collagen IV in basement membranes – but BM is ubiquitous?
• Treatable by severe immunosuppression and
plasmaphoresis (dialysis of plasma - filters plasma - bags of plasma that get replaced into patient - plasma transfusion. Circulating antibody that is causing the problem is removed) if caught early
Descrive vasculitis
- Group of systemic disorders - can cause blindness, renal failure, stoke like symptoms
- No immune complex antibody deposition
- Association with Anti Neutrophil Cytoplasmic Antibody (ANCA - anti neutrophil cytoplasmic antibody - can stain for this)
- Nephritic presentation (RPGN)
- Treatable, again if caught early
- Urgent biopsy service
Describe the pathogenis of vasulitis
ANCA attacks neutrophil which attacks lining ss for hits
