Flashcards in Glomerulonephritis Deck (39):
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?
By what extrinsic mechanisms can glomerulonephritis be caused?
- bind to mesangial cells and cause them to release cytokines and GFs
Other infiltrating cells
By which intrinsic mechanisms can glomerulonephritis be caused?
e.g. TGF-beta, PDGF, interferon-gamma
What part of the kidney can be a possible target for injury?
Integrity of glomerulus and tubules
Why can end-stage kidney failure happen even when the primary insult is removed?
- 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)
How is glomerulonephritis treated?
Control the precipitating factor
Remove Ab/IC and block Abs
Suppress the response to injury
- cytotoxics (cyclophosphamide)
- block matrix
- treatment to slow fibrosis
- slow progression
Name some of the clinical syndromes/presentations of glomerulonephritis.
- reduced GFR (increased serum creatinine)
- decreased serum albumin
- hyperlipidaemia ( as liver trues to correct the albumin)
Rapidly progressing glomerulonephritis
- due to vasculitis
- normal to end stage within 6 weeks
Name some histological features of ESKF.
- lots of cells
- increased mitotic index
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?
IgA nephropathy (most common)
Membranous GB change disease (most common cause of nephrotic syndrome in children)
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?
Urinary RBC casts
What would you expect to see on biopsy if someone has post-infectious glomerulonephritis?
Proliferation of all glomerular cells
How is post-infectious glomerulonephritis treated?
- 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
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?
What does IgA nephropathy present with?
How is IgA nephropathy treated?
- decrease proteinuria
Name some of the possible causes of membranous glomerulonephritis.
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)
What are the clinical features of membranous glomerulonephritis?
- decreased albumin
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.
- frusemide (oedema)
- ACE inhibitors (hypertension)
- antihypertensive therapy
- high dose steroids (prednisolone) and chlorambucil (for prevention of B/plasma cell proliferation and antibody production)
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)
- vasculitis of the small blood vessels
Wegeners granulomatosis - midline granulomas (nose, lungs and kidneys)
What are the symptoms of Wegener's granulomatosis?
- bleeding, stuffiness and deafness
- opacities and haemorrhage
- nephrotic/nephritic symptoms
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?
Septrin - prevents antibody production
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
How can minimal change disease be diagnosed?
- foot process fusion
- 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
- oedema decreases circulating blood volume and drops GFR
- decreased albumin
What is the treatment for minimal change disease?
High dose steriods
- prednisolone 40-60mg for 8 weeks
Cyclosphosphamide if they have multiple relapses
Cyclosporine (targets T-cells)