Glomerulonephritis Flashcards
What are the different components of the basement membrane? What is it most permeable to and why?
- Fenestrated endothelium
- Glomerular basement membrane
- Foot processes of epithelial with slit diaphragms between them
Small positive charged molecules due to it being a negatively charged barrier
I.e. water and salts able to cross most freely across the barrier
What substances fills the fenestrae of the endothelium and what is its role?
Glycocalyx
-mesh work lining the endothelium of the glomerular capillaries to act as component of basement membrane filter
What are the 4 different classifications of glomerular lesions based on degree of glomerular involvement?
Focal= <50% of all glomerular involved
Diffuse= >50% of all
Segmental= <50% of individual glom
Global= >50% individual glom involved
In what ways might a glomerular disease present?
Acute renal impairment
Chronic renal impairment
Asymptomatic haematuria
Asymptomatic proteinuria
Nephrotic syndrome
Why does nephrotic syndrome lead to oedema?
Increase loss of albumin (protein) from kidneys leads to loss of oncotic pressure in serum
Therefore decreased ability to retain water in blood so water diffuses done osmotic gradient into tissues= oedema
What are the 2 main type of glomerular disease?
Based on CAUSE:
1= primary-> disease effecting the glomeruli directly
2= secondary-> damage to glomeruli occur secondary to systemic disorder
What systemic disorders are associated with causing glomerular disease?
Diabetes mellitus
SLE
Vasculitis
Amyloidosis (abnormal protein deposition)
Hypertension
What are 3 possible routes for primary glomerular disorder to occur? What is the outcome of all 3?
- Specific antibody against part of glomeruli
- Antibody against something deposited in glomeruli
- Deposition of circulating antigen-antibody complex
Induce immune mediated inflammatory response
What occurs as a consequence of the immune mediated inflammatory response in primary glom disorders?
- Complement activation and neutrophil/macrophages/lymphocyte accumulation
- Mesangial cells activated-> secrete factors which exacerbate inflammation
- platelet thrombi form and block capillary loops
THEREFORE:
-induction of hypercellular and inflammatory state with release of chemokines and cytokines which will recruit more cells
== decreased GFR + ECM production (scarring)
What are the main histological changes in primary glomerular disorders and why do they occur?
Hypercellularity
- proliferation of mesangial, endothelial and epithelial cells
- leukocyte infiltration
- formation of crescents due to accumulation of cells in Bowman’s space
Basement membrane thickening
-accumulation of immune complexes
Hyalinisation + sclerosis (more chronic picture)
Signs of bleeding i.e. RBC casts in tubules
What are the main types of glomerulopathies?
How might someone with a glomerulopathy present?
- Acute glomerulonephritis
- Nephrotic syndrome
Haematuria Raised creatinine= main sign Raised urea Oliguria (decreased urine output) May have proteinuria Hypertension +/- oedema
What are the 2 main causes of acute glomerulonephritis?
- Post-infectious= post-streptococcal GN
- occurs in children most commonly due to streptococcal infecton leading to deposition of streptococcal antibodies
I.e. HX of streptococcal infection w/i last 1-3 weeks - Necrotising/cresenteric
- >50% of glomerular tuft destroyed in these patients
- associated with 3 different rare conditions (anti-GBM/Immune complex mediated/ANCA associated)
What is nephrotic syndrome?
How might someone present clinically?
What are the 3 types?
Nephrotic syndrome referes to a group of symptoms without a specific underlying cause but all have the same presenting criteria
Clinical criteria (i.e. how they will present)
- peripheral oedema
- proteinuria >3g/24hrs
- serum albumin <25g/L
- hypercholesterolaemia
Membranous nephropathy
Minimal change disease
Focal segmental glomerular sclerosis (FSGS)
What is membranous nephropathy?
What are the most common and secondary causes?
What demographcis is this disease likely to present in?
Diffuse thickening of GBM due to subepithelial immune complex deposition (IgG and complexes)
Most common:
- 85% idiopathic i.e. AI
- secondary to drugs, malginancy and RA
Bimodal presentation
-20s and 60s
What is minimal change disease?
When does it typical occur?
What would you expect to find on light microscopy?
Does it respond to steroids?
EM fusion of the epithelial foot processes but this isnt diagnostic because this could occur in anyone presenting with proteinuria
Typically occurs following a respiratory infection in children or in adults in relation to lymphoma, leukaemias and NSAIDs
NORMAL glomeruli on light micropscopy due to there not being depositis associated with this disease
Responds to steroids
What needs to be ruled out when an adult presents with nephrotic syndrome in the absence of AI antibodies?
Need to rule out maligancy due to it being associated with causing minimal change disease and memebranous nephropathy
What is FSGS and what is the cause?
What complications are associated with FSGS?
Does it respond to steroids?
Focal segmental glomerular sclerosis
Caused by podocytes depletion
Can lead to end-stage renal failure
Poor response to steroids
What are the possible sites of problems which lead to the podocytopathy associated with FSGS?
Podocyte transcription factor
Actin cytoskeleton
Slit diaphragm
Adhesion molecules between podocytes and GBM
What is IgA nephropathy?
How might someone present?
Most common primary GN worldwide and is caused by IgA deposits in the mesangium
Might present with haematuria with normal renal function
Can lead to acute glomerulonephritis if it causes necrosis of the glomerulus.
Peak presentation in 20s
What is Alports syndrome?
What additional conditions might someone present with?
Genetic disorder of genes for collage EM leading to defective GBM synthesis
Causes variable thickness of GBM and it can have splits
Nerve deafness and eye disorders
What is thin glomerular basement membrane disease?
What might a patient present with?
Thinning of the GBM with histologically normal glomeruli
Haematuria with normal renal function
What are the possible causes of chronic glomerulonephritis?
End stage of acute glomerulonephritis
-can be 1st presentation of acute GN due to it being subclinical in acute phase
Chronic renal failure
Small symmetrical kidneys
Diffuse granular surface
What are the most common causes of GN in children and adults?
Children:
-minimal change disease
Adults
-focal segmental glomerulosclerosis
What is Goodpasture syndrome?
How might someone typically present and why?
AI conditions= anti-GBM antibodies attack the glomerulis and pulmonary basement membranes
Presents with:
Acute kidnet failure
-due to inducing glomerulonephritis
Haemoptysis
-due to destruction of pulmonary basement membranes leading to pulmonary haemorrhage
