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
How can most GN be treated?
Immunosuppresion-> steroids
Blood pressure control -> ACEi and ARBs
What is the difference between nephritic syndrome and nephrotic syndrome?
NOTE: both refer to a clinical picture + group of symptoms rather than strict diagnosis
Main difference is that nephritic syndrome does not have set criteria but instead has associated features
NEPHRITIC
- haematuria i.e. microscopic or macroscopic
- oligouria
- proteinuria
- fluid retention
NEPHROTIC (must fufill criteria for diagnosis)
- Peripheral oedema
- Proteinuria
- Serum albumin < 25g/L
- Hypercholesterolaemia
What is the difference between glomerulonephritis and interstitial nephritis?
GN
-conditions causing inflammation around glomerulus and nephron
IN:
-inflammation of interstitium between cells and tubules within kidney
What is glomerulosclerosis?
What can cause it?
Term used to describe the scarring and damage to the glomerulus due to other conditions rather than diagnosis itself
Causes:
- GN
- diabetic neuropathy
- obstructive atrophy
- FSGS
What systemic conditions can lead to lesions to the glomeruli?
Diabetes= Diabetics neuropathy
Amyloidosis
SLE
Hypertension
What is diabetic nephroparhy?
What is a key presenting feature?
How are these patients managed?
What is the diagnostic marker on histology?
Chronically high levels of glucose passing through the glomerulus causes scarring and thickening of the GBM= glomerulosclerosis
(Most common glomerular pathology and cause of CKD in UK)
Proteinuria= due to damage to glomerulus allowing protein to pass from blood into urine
Management:
-optimise diabetes control
-BP control i.e. ACEi
NOTE: ACEi should be started in diabetic neuropathy patients even if they have normal blood pressure
Histology:
-Kimmelstiel-Wilson Nodules
Why does amyloidosis cause GN?
How is it identified with microscopy?
What are the 2 different types and what is the difference between them?
Leads to deposition of proteinaceous materal in tissues
Congo red positive and birefringence under polarised light
Primary:
-associated with light chains which occur in multiple myeloma
Secondary:
-chronic disease leading to amyloid A protein (phase reactant protein) being deposited i.e. TB or Crohns
(Conditions associated with long standing inflammatory response)
What can SLE lead to GN?
Deposition of immunoproteins i.e. IgG, IgM, IgA and complement
Can mimic multiple different types of nephropathy due to effecting the mesangial/subepithelial/subendothelial
Why does hypertension lead to glomerular disease?
What types of kidney pathology is it associated with?
Due to causing thickening of intima leading to narrowing of lumen of arteries and arterioles
-leads to decreased oxygen supply to the distal end of tubule
Glomerular sclerosis
Tubular atrophy
Interstitial fibrosis
I.e. due to ischaemic changes to kidney
