Session 9 - Glomerular damage Flashcards Preview

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Flashcards in Session 9 - Glomerular damage Deck (48)
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What are the main foci of kidney disease?

• Glomerulus
• Interstitium
• Vascular supply


What is a primary glomerular injury?

• One which just effects the glomerulus


What is a secondary glomerula injury?

• A systemic illness which happens to effect the glomerulus


What are the four main sites of glomerular injury?

• 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


Why can the nephron be termed a "functional unit"

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


What are the two main pathologies of the glomerulus?

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


What is proteinuria?

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


What does proteinuria indicate?

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


What is nephrotic syndrome?

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

Soon becomes hypoalbuminaemia


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

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


What is nephritic syndrome?

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


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

• Subepithelial
• With GBM
• Subendothelial
• Mesangial


What is the difference between primary and secondary kidney disease?

• Primary kidney disease - Pathology soley affecting kidney
• Secondary kidney disease - Systemic disease which affects kidney


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

• Podocyte/subepithelial damage


Give three primary causes of proteinuria/nephrotic syndrome

• Minimal change glomerulonephritis
• Focal segmental glomerulosclerosis
• Membranous glomerulonephritis


Give two common secondary cuases of proteinuria/nephrotic syndrome

• Diabetes mellitus
• Amyloidosis


When does minimal change glomerulnephritis occur?

• Occurs in childhood/adolescence
• Incidence reduces with increasing age


What are the symptoms of glomerulonephritis?

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


Why does minimal change glomerulonephritis occur?

• Podocytes destroyed, loss of filtration slits


What is the pathogenesis of minimal change glomerulonephritis?

• Unknown circulating factor damaging podocytes
• No immune complex deposition


Why is minimal change glomerulonephritis called thus?

• Normal golmeurli under a light microscope


How can you detect minimal change glomerulonephritis?

• Electron microscope, damage to podocytes evident


What is Focal segmental glomerulosclerosis

• Nephrotic syndrome which effects adults
• Steroids minimally effective


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

• Massive proteinuria
• Haematuria
• Hypertension
• Renal failure


Why is it called focal segmental glomerula sclerosis?

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


What is the main pathology of Focal segmental glomerulosclerosis?

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


What causes Focal segmental glomerular nephritis?

• A circulating factor


What is membranous glomerulonephritis?

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


What causes membranous glomerulonephritis?

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


What is an immune complex?

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


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

• Progressive proteinuria

Progressive renal failure


How does the rule of thirds apply to membranous glomerulonephritis?

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


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

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


What is nephritic syndrome?

• Renal failure due to blocking of filter


Give five causes of nephritic syndrome

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


What is IgA nephropathy?

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


How does IgA present?

• 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


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

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


What happens to the mesangium in IgA nephropathy?

Mesangial proliferation and scarring


Give two types of hereditatary nephropathy

• Thin GBM Nephropathy
• Alport syndrome


Outline thin GBM nephropathy

Isolated Haematuria
Thin GBM
Benign Course


What is alport?

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


What is Goodpasture Syndrome?

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


What is the pathology behind goodpasture syndrome?

• Autoantibody to collagen IV in basement membranes

Characterised by IgG deposition but no extracellular matrix deposit


How is goodpasture syndrome treated?

• Treatable by immunosupression
• Plasmaphoresis

Take patients blood out, remove plasma with IgG in and then exchange plasma


What is vasculitis?

• 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


What is a subepithelial deposit?

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


What is a mesangial deposit?

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