Glomerulonephritis Flashcards
What is glomerulonephritis?
Inflammatory diseases involving the glomerulus and tubules of the kidney
May be primary or secondary
What are the mesangial cells of the kidney?
Modified smooth muscle cells.
Capable of contraction to regulate the blood flow and decrease the surface area of the basement membrane (decrease GFR)
Produce the mesangial matrix for structural support of the capillaries in the glomerulus
Describe what structures filtrate have to pass through to get from the blood into the tubules.
Fenestrated capillary membrane (endothelium)
Glomerular basement membrane
Podocyte (epithelial cell)
What are the two categories of pathological mechanisms that can cause glomerulonephritis?
Extrinsic mechanisms
Intrinsic mechanisms
By what extrinsic mechanisms can glomerulonephritis be caused?
Antibodies - bind to mesangial cells and cause them to release cytokines and GFs Immune complexes Complement Cytokines Lymphocytes Other infiltrating cells
By which intrinsic mechanisms can glomerulonephritis be caused?
Cytokines Growth Factors e.g. TGF-beta, PDGF, interferon-gamma Vasoactive factors Proteinuria
What part of the kidney can be a possible target for injury?
Mesangial cells Basement membrane Epithelial cells Endothelial cells Vasculature Tubular structures Integrity of glomerulus and tubules
Why can end-stage kidney failure happen even when the primary insult is removed?
Hyperfiltration theory
- some of the kidney is destroyed
- parts of the kidney that are left are overworked to try and take over the work of the dead cells
- eventually are exhausted and die as well
- end-stage kidney failure
Name some predictors of whether an acute insult may lead to ESKF.
Hypertension - glomerular and systemic Baseline GFR, serum creatinine Biopsy - extent of glomerulosclerosis Biopsy - extent of tubular loss/interstitial fibrosis (relates to glomerular damage) Age Primary disease
How is glomerulonephritis treated?
Control the precipitating factor Remove Ab/IC and block Abs Suppress the response to injury - steroids - cytotoxics (cyclophosphamide) - block matrix - anti-hypertensives Manage ESRF - treatment to slow fibrosis - dialysis - transplant - slow progression
Name some of the clinical syndromes/presentations of glomerulonephritis.
Proteinuria Hypertension Haematuria Renal impairment - reduced GFR (increased serum creatinine) Nephrotic syndrome - proteinuria - decreased serum albumin - oedema - hyperlipidaemia ( as liver trues to correct the albumin) Nephritic syndrome - hypertension - haematuria - oligouria Rapidly progressing glomerulonephritis - due to vasculitis - normal to end stage within 6 weeks
Name some histological features of ESKF.
Rapid proliferation
- lots of cells
- increased mitotic index
Glomerulosclerosis
What are crenated RBCs?
RBCs that have become crenated by hyper-concentrated urine (glomerular destruction)
Look like WBCs on microscopy
What is a RBC cast?
A tube shaped aggregation of RBCs
- a sign of bleeding in the kidney
- a sign of aggressive glomerulonephritis
(Renal tubular epithelial casts indicate severe renal tubular necrosis)
What are the main types of glomerulonephritis that you need to know?
Post-infectious GN IgA nephropathy (most common) Membranous GB change disease (most common cause of nephrotic syndrome in children) RPGN/Crescentic GN/Vasculitis Diabetic nephropathy
Describe the progression of post-infectious glomerulonephritis to ESRF.
Infected (streptococci) and Ab/IC produced
Deposition of Ab/IC in the mesangium
Complement activated (hypocomplementaemia) and leukocytes infiltrate
This causes glomerular cell destruction and proliferation of epithelial cells (crescent formation)
Eventually this leads to glomerulosclerosis, tubular loss and hypertensive damage
What are the clinical features of post-infectious glomerulonephritis?
Haematuria Proteinuria Oedema Hypertension Renal impairment RPGN Urinary RBC casts
What would you expect to see on biopsy if someone has post-infectious glomerulonephritis?
Proliferation of all glomerular cells
Infiltrating lymphocytes
How is post-infectious glomerulonephritis treated?
Antibiotics
- penicillin if strep
- broad spectrum for other causes
Dialysis - if it doesn’t resolve after a few weeks (most cases)
Describe the progression of IgA nephropathy from normal to ESRF.
(Infection?) - production of IgA - deposited in the mesangium Lysis of mesangium Proliferation of mesangium cells - matrix produced - healing or scarring occurs Glomerulosclerosis Tubular loss Hypertensive damage
How is IgA in IgA nephropathy produced?
Precipitated by infection
- abnormal IgA is produced by the Peyer’s patches
What diseases can IgA nephropathy be secondary to?
Henoch-Schönlein purpura
Cirrhosis
Coeliac disease
What does IgA nephropathy present with?
Haematuria
Hypertension
Proteinuria
How is IgA nephropathy treated?
Antihypertensives
- decrease proteinuria
ACE inhibitors
Name some of the possible causes of membranous glomerulonephritis.
Tumour Drugs - gold and penicillin Hepatitis B and C Connective Tissue Disease Idiopathic - 90%
Describe the progression of membranous glomerulonephritis from normal to ESRF.
Production of immune complexes and antibodies
- IC deposited in the GBM and mesangium
Alters the GBM charge, and permeability (proteinuria)
Thickened GBM
Glomerulosclerosis
Tubular loss
Hypertensive damage
What are the clinical features of membranous glomerulonephritis?
Proteinuria Nephrotic syndrome - proteinuria - decreased albumin - oedema - hyperlipidaemia Hypertension Renal impairment
What is the outcome of membranous glomerulonephritis?
Third - remit
Third - progress to ESRF over 1-2 years
Third - persistent proteinuria, but maintained GFR
Describe the specific and non-specific therapies for membranous glomerulonephritis.
Non-specific - frusemide (oedema) - ACE inhibitors (hypertension) - antihypertensive therapy - NSAIDs - statins Specific therapy - high dose steroids (prednisolone) and chlorambucil (for prevention of B/plasma cell proliferation and antibody production) Cyclophosphamide/Azathioprine RITUXIMAB (anti-CD20) Underling disease
What are rapidly progressing glomerulonephritises?
A group of conditions linked by natural history and histology
- crescents on biopsy
- progression to ESRF after a few weeks
Name some causes of RPGN.
Good pastures syndrome - Ab against basement membrane (lungs and kidneys) Polyarteritis nodosa - vasculitis of the small blood vessels Wegeners granulomatosis - midline granulomas (nose, lungs and kidneys) Post-infectious/bacterial endocarditis Lupus Idiopathic
What are the symptoms of Wegener’s granulomatosis?
Nasal symptoms - bleeding, stuffiness and deafness Pulmonary symptoms - opacities and haemorrhage Kidney symptoms - nephrotic/nephritic symptoms Systemic features
What are the biochemical/histological features of Wegener’s granulomatosis?
Urinary RBC casts
Anti-neutrophil cytoplasmic antibodies (ANCA)
Crescent around the glomerular capillaries
What is the treatment for Wegener’s granulomatosis?
Steriods
Cytotoxics
Septrin - prevents antibody production
Transplant
What is the pathophysiology of minimal change disease?
T-cell and cytokine mediated
Targets the glomerular epithelial cells, and changes the GBM charge
Glomerular filtration barrier is affected
- proteinuria
How can minimal change disease be diagnosed?
Light microscopy - normal Electron microscopy - foot process fusion Immunoflourescence - C3 (high due to active disease state) - IgM depsosition
What are the clinical signs of minimal change disease?
Acute - following URTI GFR - normal or reduced due to intravascular depletion Renal failure - oedema decreases circulating blood volume and drops GFR Nephrotic syndrome - proteinuria - decreased albumin - hyperlipidaemia - oedema
What is the treatment for minimal change disease?
High dose steriods - prednisolone 40-60mg for 8 weeks THEN Cyclosphosphamide if they have multiple relapses THEN Cyclosporine (targets T-cells)
What do you test on a glomerulonephritis screen and why?
U&Es - excretory functions LFTs Glucose - diabetic nephropathy CRP FBC - increased WCC in infection ESR Urinalysis and microscopy - blood and protein Urine protein PCR Antibodies: ANF (lupus), RF (CTD), anti-GBM and ANCA (vasculitis) Complement (decreased in RPGN and lupus) Immunoglobulins A, M, G and electrophoresis (myeloma) Coagulation (to see if they can have a biopsy) Hep B, C HIV Blood and other cultures
