Glomerulonephritis Flashcards
what is glomerulonephritis?
Immune mediated disease of the kidneys affecting the glomeruli
what is the summary pathophysiology of the glomerulonephritis?
- Damage to the glomerulus restricts blood flow, leading to compensatory raised BP
- Damage to the filtration mechanism allows protein and blood to enter the urine
- Loss of the usual filtration capacity leads to acute kidney injury
what are the types of primary glomerulonephritis?
o Minimal change o FSG o Membranous o IgA neuropathy o Membranoproliferative
what are the causes of secondary glomerulonephritis?
caused by infections of drugs, associated with malignancy, or part of systemic disease
what are the histological classifications of glomerulonephritis?
- Proliferative or non-proliferative
- Focal/diffuse
- Global/segmental
- Crescenteric
what are the common clinical features of GN?
- Haematuria
- Proteinuria
- Impaired renal function – AKI, CKD, ESRD
- Nephritic or Nephrotic
- Weakness, fatigue, anorexia, nausea, vomting, abdo pain, joint pain
what are the two types of treatment for GN?
non-immunosuppressive
Immunosuppression
what are the features of non-immunosuppressive management of GN?
o Anti-hypertensives (target <130/80,
what are the changes to BP in nephrotic syndrome?
Normal-mildly ↑
what are the changes to BP in nephritic syndrome?
Moderate-severely ↑
what are the changes to urine in Nephrotic syndrome?
Proteinuria > 3.5g/dy
what are the changes to urine in Nephritic syndrome?
Haematuria (mild-macro)
what are the changes to GFR in nephrotic syndrome?
Normal-mild ↓
what are the changes to GFR in nephritic syndrome?
Moderate-severe ↓
what are the primary causes of nephrotic syndrome?
minimal change disease, focal segmental glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, rapidly progressing glomerulonephritis
what are the secondary causes of nephrotic syndrome?
diabetic nephropathy, SLE, sarcoidosis, syphilis, Hep B, Sjogren’s Syndrome, HIV, amyloidosis, Multiple myeloma, vasculitis, cancer, congenital nephrotic syndrome, drugs (penicillin)
what is the pathophysiology of Nephrotic Syndrome?
- Effects podocytes
- Indicates non-proliferative process
- Allows proteins to pass into urine
what are the mechanisms of proteinuria in nephrotic syndrome?
o In response to hyperlipidaemia
o >oncotic pressure – osmotic drive
o Damage causes < permeability
what are the clinical features of nephrotic syndrome?
- Proteinuria>3g/day (mostly albumin, also globulins)
* Hypalbuminaemia (<30), oedema, hypercholesterolaemia, normal renal function, hyperlipidaemia, lipiduria
what are the complications ofnephrotic syndrome?
infections, renal vein thrombosis, PE, volume depletion
what is the management of nephrotic syndrome?
General – fluid restriction, salt restriction, diuretics, ACE/ARBs, anticoagulation, IV albumin
Immunosuppression
what are the causes of nephritic syndrome?
- IgA neuropathy
- Mesangiocapillary
- Post streptococcal glomerulonephritis
- Rapidly progressive glomerulonephritis
- Vasculaitis, SLE, cryralbuminaemia
what is the pathophysiology of nephritic syndrome?
- Affecting endothelial cells
- Indicative of a proliferative process
- Damage done by antibody/antigen complex – urinary casts formed
what are the clinical features of nephritic syndrome?
acute renal failure, oliguria, oedema, hypertension, active urinary sediment – RBCs, RBC and Granular cells = HAEMATURIA + PROTEINURIA
what is the cause of minimal change glomerulonephritis?
idiopathic, associated with Hodkins Lymphoma, NSAIDs, rifampicin, mono
what is the pathophysiology of Minimal Change Glomerulonephritis?
T cells release cytokines (IL-13) that target and damage podocytes – makes them flatter = effacement. Results in loss of charge barrier. Albumin can pass through but not larger proteins
what are the clinical features of minimal change glomerulonephritis?
nephrotic syndrome, normotension, proteinuria
what are the histological features of minimal change biopsy?
normal renal biopsy on LM & IF, foot process fusion on EM
what is the management of minimal change glomerulonephritis?
oral steroids (94% complete remission), 2nd line = cyclophosphamide, majority reoccur
what are the primary causes of focal segmental glomerulosclerosis?
unknown
what are the secondary cayses of focal segmental glomeruloscelroiss?
sickle cell, HIV, heroin, kidney hyper fusion, increased pressure in glomerular capillaries, obesity, reflux, renal transplant reoccurrence
what is the pathophysiology of focal segmental glomerulosclerosis?
podocytes are damaged allowing plasma and proteins to enter glomerulus, overtime can become trapped and build up in glomerulus = hyalinises, can progress to sclerosis – only occurs in part of and some of glomeruli
what are the clinical features of Focal Segmental Glomerulosclerosis?
nephrotic syndrome
what are the histological features of Focal Segmental Glomerulosclerosis?
focal and segmental sclerosis and hylaniosis on LM, minimally on IF, effacement of podocytes on EM
what is the management of Focal Segmental Glomerulosclerosis?
Steroids +/- immunosuppressants
what is the epidemiology of Membranous Glomerulonephritis?
• Most common type in adults
what is the primary cause of Membranous Glomerulonephritis?
idiopathic
what are the secondary causes of Membranous Glomerulonephritis?
infections (hep B/parasites), connective tissue disease, cancers, drugs (penicillin’s/gold), malignancy
what is the pathophysiology of Membranous Glomerulonephritis?
o Autoantibodies targeting GBM (Anti-PLA2r antibody) form immune complexes and deposit in sub epithelial space
o Activates compliment system – membrane attack complex attacks podocytes and mesangial cells = become more permeable (proteins enter)
o Over time GBM matrix is deposited between complexes = thickening
what are the clinical features of Membranous Glomerulonephritis?
2nd most common cause of nephrotic syndrome
what is the histological appearance of Membranous Glomerulonephritis?
spike and dome appearance
what is the management of Membranous Glomerulonephritis?
ACE/ARB, immunosuppression, anticoagulation
what is the prognosis of Membranous Glomerulonephritis?
rule of 1/3 – 1/3 spontaneous remission, remain proteinuria, ESRF
what is the immunosuppressive management of Membranous Glomerulonephritis?
steroids/alkylating agents/ B cell monoclonal AB
what is membranoproliferative glomerulonephritis also known as?
MESANGIOCAPILLARY GLOMERULONEPHRITIS
what is the cause of Type 1 Membranoproliferative glomerulonephritis?
cryoglobinaemia, Hep B, Hep C
what is the cause of Type 2 Membranoproliferative glomerulonephritis?
partial lipodystrophy, factor H deficiency
what is the cause of Type 3 Membranoproliferative glomerulonephritis?
hep B and C
what is the pathophysiology of Type 1 Membranoproliferative glomerulonephritis?
Immune complex deposition from chronic infection or mutation of antibody against complement system proteins
C3 convertase enzyme binds to IgG
Release oxidants + proteases causing damage of endothelium, thickening of B
what is the pathophysiology of Type 2 Membranoproliferative glomerulonephritis?
dense deposit disease
Nephritic factor (stabilises C3 convertase) – anti C3bBb, C3NeF
Only compliment deposits, no immune complexes
Low circulating levels of C3
what is the pathophysiology of Type 3 Membranoproliferative glomerulonephritis?
immune complexes and complement deposit in subepithelial and subendothelial
what are the histological features of Type 1 Membranoproliferative glomerulonephritis?
tram track appearance, glomeruli appear granular
what are the histological features of Type 2 Membranoproliferative glomerulonephritis?
reduced serum compliment deposits, no immune complexes
what are the clinical features of Type 3 Membranoproliferative glomerulonephritis?
nephrotic + nephritic
what is the management of Type 3 Membranoproliferative glomerulonephritis?
steroids
IgA nephropathy is also known as…
Bergers Disease
what is the epidemiology of IgA nephropathy?
• Most common cause of glomerulonephritis
what is the cause of IgA nephropathy?
often occur after GI/Resp infection – ½ days
o Associated with: alcoholic cirrhosis, coeliac, Henoch-Schonlein purpura
what is the pathophysiology of IgA nephropathy?
o Abnormal glycosylation of IgA1 antibodies
o Body also recognises them as non-self-produce IgG (anti-IgA1) that form complexes that deposit in mesangial
o Causes complement activation, cytokine release, macrophage mutation
o Also causes mesangial proliferation, glomerular sclerosis, interstitial fibrosis
what are the clinical features of IgA nephropathy?
o Macroscopic haematuria
o Asymptomatic microhaematuria +/- non nephrotic range proteinuria
o Nephritic syndrome + associated Henock Schoenlein Purpura
what are the histological features of IgA nephropathy?
mesangial hypercellularity, positive immunofluorescence for IgA & C3
how is IgA nephropathy managed?
BP control/Ace inhibitors & ARBS/ Fish oil
what is Henoch-Schonlein Purpura?
Systemic variant of IgA Nephropathy
what are the clinical features Henoch-Schonlein Purpura?
Systemic variant of IgA Nephropathy
what is post Streptococcal Nephropathy also known as?
Proliferative Glomerulonephritis
what is the cause of
Post Streptococcal Nephropathy?
Group A, B-haemolytic streptococci
what is the pathophysiology of Post Streptococcal Nephropathy?
o Immune complexes of antigen + IgG/IgM form + travel to glomerulus or antigen travels to glomerulus and complexes form there
o Affects BM (subepithelial layer)
o Activation of C3 complement, cytokines, oxidates, proteases causing damage to podocytes – all proteins + red blood cells pass through
what are the clinical features of Post Streptococcal Nephropathy?
headaches, malaise, haematuria, proteinuria, hypertension, oliguria, periorbital oedema – NEPHRITIC Syndrome
what is the histology of Post Streptococcal Nephropathy?
diffuse proliferative glomerulonephritis, endothelial proliferation with neutrophils, EM shows subepithelial humps, IF granular or starry
what are the differences between IgA vs Post Strep
1-2 days vs 1-2 week
UTI, young males vs URTI
macroscopic haematuria vs proteinuria
Rapidly Progressing Crescenteric Glomerulonephritis is known as…
• Most aggressive
what is the cause of Type 1 Rapidly Progressing Crescenteric Glomerulonephritis?
anti-GBM – good pastures syndrome
what is the cause of Type 2 Rapidly Progressing Crescenteric Glomerulonephritis?
immune complex mediated – post strep, lupus (ANCA +ve or -ve), IgA nephropathy
what is the cause of Type 3 Rapidly Progressing Crescenteric Glomerulonephritis?
ANCA (cANCA = Wegners, pANCA = Chung Strauss syndrome)
what is the pathophysiology of Rapidly Progressing Crescenteric Glomerulonephritis?
o Inflame mediators, C3b, fibrin pass into Bowmans space as well as macrophages + monocytes and parietal epithelial cells
o Proliferation leads to expansion of epithelial layer into thick crescent shape – scarring + sclerosis, glomerular damage = reduced GFR
what are the clinical features of Rapidly Progressing Crescenteric Glomerulonephritis?
nephritic syndrome, symptoms associated with cause disease, AKI + systemic symptoms, frank haematuria
what are the IM features of Rapidly Progressing Crescenteric Glomerulonephritis?
Type 1 = linear
Type 2 = granular
Type 3 = negative
how is Rapidly Progressing Crescenteric Glomerulonephritis managed?
immunosuppressants (steroids = prednisolone, cytotoxic = azathioprine), plasmapheresis
what are the additional clinical features of Good Pastures syndrome?
kidney problems then massive pulmonary bleed,
