Glomerulonephritis Flashcards
Nephrotic syndrome - what?
- Massive proteinuria (leads to)
- Hypoalbuminemia (leads to)
- Edema
- Hyperlipidemia/hyperlipiduria
Nephritic syndrome - what?
Inflammation related
- Hematuria inflammation allows leak of rbc into filtrate
- Haemodynamic changes lead to reduced GFR leads to Oliguria and
- Azotemia (increased nitrogen containing compounds eg urea in blood)
- Hypertension (due to water retention and increased renin from ischaemic kidneys)
Basic pathophysiology
Diseases involving glomeruli largely immune mediated
Maybe be auto-antibody, antigen-antibody complexes may implant themselves in the glomerulus, T-cells don’t really play a role
What is the glomerulus?
Cluster of capillaries in Bowman’s capsule at end of a nephron
3 layers - capillary endothelial cells, basement membrane, podocyte cells
What does the glomerulus do?
Filtration
About 20% of blood volume that passes through
BIG molecules (eg protein) don’t pass through sieve
Glomerulus slightly negatively charged so quite small negative things also don’t pass through (eg albumin) positive things do
Very small things pass even if negative eg chloride
Also determined by the pressure
Presentation of glomerular disease
Nephrotic or nephritic syndrome or rapidly progressive glomerulonephritis
Causes of nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis
Basic pathophysiology of the nephrotic syndromes
Derangement in walls of the capillaries - proteins escape into filtrate
Usually relating to podocytes - often effaced (flattened) and as change shape the filtration slits between adjacent podocyes are damaged - proteins escape!
Minimal change disease
More common in children
Not (m)any changes under microscope
On electron micrographs, podocytes appear flattened - foot processes are fewer and effaced
Most children with minimal change disease respond well to steroids, some relapse and a few develop CKD as adults
Focal segmental glomerulosclerosis
Only some glomeruli involved (focal)
Usually only a portion of the glomerulus is damaged (segmental)
Can be primary (idiopathic) or related to other conditions (HIV/heroin), some arise from other forms of glomerulonephritis, rare cases are hereditary.
Exact mechanism unclear
Initiating event is podocyte injury
Proteins leak out of blood -> collect in places -> form masses of hyaline (pink) material -> encroach on or obliterate capillaries
Poor prognosis, poor response to steroids
Membranous nephropathy aka membranous glomerulonephritis
Antibodies react to antigen in the glomerulus > antigen-antibody complexes > deposit selves in glomerular basement membrane
Capillary walls thicken as immune complexes accumulate
Damage > complement release > podocyte damage > protease and oxidant release > capillary wall damage > permeability
Most cases idiopathic
Clinical course variable
Often mild
Membranoproliferative glomerulonephritis (MPGN)
Two types:
Type 1: characterised by subendothelial (and sometimes subepithelial/mesangial) immunoglobulin and complement deposits
Type 2: characterised by deposits of complement in basement membrane proper
Both: Thickened GBM on light microscopy, looks like GBM split in two in silver stain (due to mesangial and inflammatory cells stuck)
Associated with infection or idiopathic
Prognosis generally poor
Causes of nephritic syndromes
Acute infectious (post-streptococcal) glomerulonephritis IgA nephropathy (Berger disease) Hereditary nephritis
Basic pathophysiology of Nephritic syndromes
Proliferation of cells within glomeruli along with inflammation in the glomerulus.
Inflammatory cells damage capillary walls > red cells leak out
Requires more pressure to pump blood through glomerulus (cos it’s stuffed full of cells) > reduced GFR > oliguria
Acute infectious (post-streptococcal) glomerulonephritis
Usually in children after group A strep
Body produces Ab to bacteria > forms Ag-Ab complex > gets stuck in glomerulus > immune response > cells proliferate
Light microscopy: glomeruli big and hypercellular
Most children recover, some develop rapidly progressive glomerulonephritis adults tend to be affected more seriously
IgA nephropathy (Berger disease)
Most common glomerular disease worldwide
Usually child or young adult
Follows URTI > haematuria > resolves > comes back every few months
Overproduction of IgA (when get URTI) > stuck in mesangium > complement activation > damage
Immunofluorescence: lots of IgA (light microscopy: varied)
Prognosis good despite recurrent haematuria
Hereditary nephritis
Group of hereditary diseases with mutations in GBM proteins.
Best known is Alport syndrome
Alport syndrome
Glomerulonephritis, deafness and eye disorders
No microscopic changes til late, then interstitial cells look foamy, glomeruli become sclerotic, tubules atrophy, interstitium becomes fibrotic.
X linked. Mutation coding type IV collagen
Male: haematuria as child/young adult; renal failure 20-50yo
Rapidly progressive (crescentic) glomerulonephritis causes
Type I (anti-GBM antibody) Type II (immune-complex mediated) Type III (pauci-immune)
RPGN basic pathophysiology
Severely oliguric and develop renal failure within a few weeks or months
(Kinda like nephritic but faster)
Mostly immune mediated
Crescent shaped masses of proliferating cells and leukocytes within glomerular tuft
Type I (anti-GMB antibody) RPGN
Linear deposition of IgG +/- complement on GBM.
Some patients: IgG also binds to basement membrane in lungs - Goodpasture syndrome
Plasmapheresis removes antibodies
Type II (immune-complex mediated) RPGN
Immune complexes found along GBM +/- mesangium
Idiopathic or evolve from post-streptococcal GN, lupus, IgA nephropathy or HSP
Plasmapheresis doesn’t help
Type III (pauci-immune)
Antineutrophil cytoplasmic antibodies (ANCAs).
Idiopathic or related to vasculitides that have ANCAs eg wegeners
Can have enough proteinuria to look like nephrotic syndrome
Plasmapheresis sometimes helpful
Investigations: bedside
Urine dipstick and microscopy - haematuria, proteinuria, sometimes RBC casts
Also, urine protein quantification: 24hr sample or prot: creatinine ratio
