Glomerulonephritis Flashcards
What are all conditions affecting the glomerulus known as?
All conditions affecting the glomerulus are called glomerulonephritis (glomerulopathy too)
What are the types of kidney diseases?
Tubulointerstitial diseases (diseases of tubules and interstitium)
Vascular diseases of the kidneys
Glomerulonephritis (not all inflammatory so some call it gomerulopathy)
What is a problem with separating the 3 diseases?
Sometimes all 3 compartments are affected and it is hard to tell where it started.
What is the second most common common cause of chronic renal failure requiring dialysis/renal transplantation?
Glomerulonephritis is the second most common cause of chronic renal failure.
(Diabetes is the most common cause of renal failure, hypertension third most common)
What is azotaemia?
Rise in creatinine/serum urea, this takes days or weeks typically. When it becomes symptomatic it is called ureamia.
When is chronic renal failure defined as end stage?
Chronic renal failure takes place over long time and is defined as end stage when eGFR is less than 5%
What is done to patients with chronic renal failure?
The idea is to maintain quality of life using dialysis for as long as possible after end stage renal failure
What are the symptoms of renal dysfunction?
Extensive list of symptoms and signs of renal dysfunction include primarily:
Lethargy
Anorexia
SOB
Peripheral neuropathy
Oedema
The actual symptoms include many more signs and symptoms that are systemic in nature due to systemic nature of kidney function
What are the prerenal factors that cause renal failure?
Factors that interfere with blood flow to kidney (example dehydration causing hypovolemia)
What are the renal factors that cause renal failure?
Damage to glomeruli, tubular or interstitium, glomerulonephritis, acute tubular necrosis, acute interstitial nephritis, tumor lysis syndrome, drug induced nephrotoxicity, contrast-induced nephropathy
What are the postrenal factors that cause renal failure?
Factors that affect urine outflow through obstruction (eg calculi)
What is nephritic syndrome?
Acute renal failure is similar
Azotemia/uraemia
Oliguria
Haematuria (often macroscopic but hard to tell by patients and urine starts to darken but doesn’t look like blood)
Mild to moderate proteinuria
Hypertension
Usually due to glomerulonephritis (until proven otherwise)
What is Rapidly Progressive Glomerulonephritis (RPGN)?
Subset of nephritic syndrome
Rapid rise in serum urea/creatinine
Usually due to crescenteric glomerulonephritis
What is nephrotic syndrome?
Nephrotic range proteinuria (>3.5g/24 hours) and low albumin in blood (caused by increased glomerular capillary permeability)
Hypoalbuminaemia (low serum protein due to losing it to the glomerulus)
Peripheral oedema (due to reduced serum oncotic pressure due to lower protein and albumin in blood causing fluid to be hypotonic to intracellular environment)
hyperlipidaemia (due to increase in hepatic lipid synthesis)
lipiduria
proteinuria
What is the primary cause of nephrotic syndrome?
Abnormal increase in permeability
What happens when the serum protein and albumin is low during nephrotic syndrome?
Liver compensates by producing more lipids causing hyperlipidaemia in response to loss of albumin and increase of water build up in the kidney due to change in oncotic pressure
What is the mesangial matrix?
Mesangial matrix is the scaffold of the glomerulus which holds the capillary loops together.
What causes the majority of glomerulonephritis syndromes?
Immune complex mediated glomerulonephritis
How can glomerulonephritis be diagnosed?
Glomerulonephritis can only be diagnosed via tissue biopsy using 3 diagnostic modalities: light microscopy, immunoflorscence (using fluorescent microscopy), and electron microscopy (extremely high magnification).
What are the types of glomerulonephritis and what causes them?
Primary no identifiable cause (idiopathic)
Secondary can be caused by drugs, infection, autoimmune disease, or malignancy
Who typically gets minimal change disease?
Usually in children
Who gets membranous nephropathy?
Membranous nephropathy is seen in middle aged males.
What happens in membranous nephropathy? What causes membranous nephropathy and what is the prognosis?
Autoantibodies to A2 receptor on the podocytes
Secondary causes: drugs, infections (HepB and syphilis), autoimmune diseases (Thyroiditis) and malignancy
40% spontaneous remission
What is focal segmental glomerulosclerosis?
Sclerosis means hardening and scarring
Fibrous adhesions to renal capsule
immunofluorescence shows segmental IgM and C3 because IgM has highest molecular heavy weight and this causes it to deposit in area of large amounts of IgM deposited passively NO IMMUNE COMPLEXES
What causes FSGS? What is the prognosis?
FSGS can be secondary to other types of glomerular nephritis. It is a sign of progression of glomerularnephritis
1/3rd will survive but the rest go to chronic renal failure
What causes post-infectious GN?
Antigen from streptococcal disease in immune complexes
What is IgA nephropathy? What are the clinical signs/symptoms? What factors are thought to precipitate it? What is the prognosis?
IgA nephropothy is called berger’s disease and affects young adults
nephritic syndrome (top of list)
Microscopic haemoturia
present with people going through medical screen for private health insurance
sometimes precipitated by URT? (synpharyngitic)
Mesangioproliferative (mesangial cell hyperproliferation)
IgA mesangial on immunofluorescence)
1/3rd resolve 1/3rd stable 1/3rd chronic renal failure
How many Australians have indicators of chronic kidney disease?
1.7 million
What age groups have the highest percentage of people with indicators of chronic kidney disease?
40% of people older than 75 years old
20% of all indigenous people older than 18 years old
How does renal disease get grouped?
Acute renal failure
Chronic renal failure
Nephritic syndrome (rapidly progressing glomerulonephritis)
Nephrotic syndrome
What is acute renal failure defined as?
Rapid rise in serum urea and creatinine over days to weeks
This rise is usually accompanied by oliguria / anuria (drop or cessation of urine production)
What is the prognosses for acute renal failure?
Can completely resolve or progress to chronic renal failure
What is chronic renal failure and how is it different to acute renal failure?
Gradual and progressive rise in serum urea/creatinine over a timespan of months to years. The longer timespan of rise in creatinine and urea is what makes it different.
What lines the inside of the bowman’s capsule?
Parietal epithelial cells
What results from immune-complex formation?
Inflammation. These complexes become trapped in the glomerulus due to its convoluted nature and high protein turnover. where the complex turns up is what determined the type of glomerulonephritis?
What happens when immune complex and inflammation occurs in mesangial cells?
They hyperproliferate and produce more mesangial matrix.
What happens when immune complexes happen along capillary loops (Subendothelial immune complexes)?
The endocapillary starts proliferating endothelial cells creating more layers of endothelial cells which further occludes the capillary loops
What happens when immune complexes occur on the epimembranou portion of the basement membrane?
Forms basement membrane spikes which blocks the holes formed by podocytes and more basement membrane is formed.
What determines where the immune complex ends up?
The molecular weight
The electrical charge
What are the secondary causes of glomerulonephritis?
Drugs
Infections
Autoimmune diseases
Malignancy
What are the types of GN diseases?
On a spectrum in which the top are most likely to be present with nephritic syndrome and the bottom are most likely to present with nephrotic syndrome:
NEPHRITIC Post-infectious GN IgA nephropathy Mesangiocapillary / membranoproliferative GN Focal segmental glomerulosclerosis Membranous nephropathy Minimal change disease NEPHROTIC
What is the pathgenesis of minimal change disease?
Structural abnormality in the podocytes.
How is minimal change disease detected?
Looks normal on light microscopy and immunofluorescence
Electron microscopy can detect the defect
What is the result of the podocytopathy in minimal change disease?
Leads to loss of protein leading to nephrotic syndrome
Swollen foot processes
What is the treatment for minimal change disease?
Highly steroid responsive especially in children
What are the secondary causes of minimal change disease?
Drugs (especially NSAIDs)
Malignancy (Hodgkin’s lymphoma)
Immunisation
What is the prognosis of minimal change disease?
Very responsive to steroids and less predictable in adults
What causes membranous nephropathy?
Immuno complex GN (subepithelial membranous GN)
Glomerular basement membrane is thickened due to depositing of substances around basement membrane
immune complexes will be seen eith IgG and C3 antibodies
How can membranous nephropathy be detected?
Electron microscopy will show deposits on basement membrane
What causes primary membranous nephropathy?
Autoantibodies to podocyte phospholipase - A2 receptor
What causes secondary membranous nephropathy?
Drugs (NSAIDs, Gold, Penicillamine, Captopril)
Infections (Hep B, schistomiasis, syphillis)
Autoimmune disease (SLE, thyoiditis)
Malignancy (Lung, colorectal, melanoma)
What is the prognosis for membranous nephropathy?
40% spontaneous remission
40% progress to chronic renal failure
What is the difference between focal and diffuse glomerular pathology?
Focal = less than 50% of all glomeruli are affected
Diffuse = more than 50% of all glomeruli
What is the difference between segmental and global glomerular pathology?
Segmental = less than 50% of an individual glomerulus
Global is greater than 50% of entire glomerulus
What is focal segmental glomerulosclerosis?
A focal and segmental nephrotic pathology in the glomerulus where there is collapse of the capillary loops with scarring and fibrous adhesions to the bowman’s capsule
How common is Focal Segmental GlomeruloSclerosis?
Most common cause of nephrotic syndrome in adults
What does immunofluorescence show with FSGS?
Segmental IgM and C3
It is not immune-complex mediated and instead is caused by trapping of large molecules in scarred segments
What does electron microscopy show with FSGS?
Segmental scarring and effacement of podocytic foot processes and no immune-complexes
What does FSGS look like under the light microscope?
Focal
Segmental
Collapse of the capillary loops with scarring and fibrous adhesions to the bowman’s capsule
What are the secondary causes of FSGS?
Can be secondary to any other glomerulnoephritis condition.
HIV, sickle-cell anaemia, heroin abuse, obesity
Any cause of nephorn loss (unilateral renal agenesis, renal ablation)
What is the prognosis of FSGS?
30% recover with steroids
Others progress to chronic renal failure
What does post-infectious glomerulonephritis look like on the light microscope?
Light microscopy would show too many mesangial endothelial cells and neutrophilic inflammation
Is post-infectious glomerulonephritis a nephritic or nephrotic syndrome?
Nephritic syndrome
What does post-infectious GN look like on electro microscope?
Electron microscope shows no spikes
What bacteria is associated most often with post-infectious GN?
Streptococcus
What is the prognosis for post-infectious GN?
95% of children recover with conservative treatment
40% of adults progress to renal failure
What kind of people get post-infectious GN most often?
Children 6 - 10 but can occur to anyone
What condition does post-infectious GN usually start as?
Pharyngitis or cellulitis
It is immune complex mediated
What antigen is associated most often with post-infectious GN?
Planted streptococcal pyogenic exotoxin B
What does post-infectious GN look like on the light microscope?
Diffuse proliferative GN
Mesangial hypercellularity
Endocapillary proliferation
Neutrophilic inflammation
What is another name for post-infectious GN?
Diffuse proliferative GN
What does post-infectious Gn look like on immunoflorescence?
Granular, mesangial and capillary loop IgG and C3
What does post-infectious Gn look like on electron microscope?
Subepithelial “humps” caused by presence of immune-complex deposits
No spikes
Why is post-infectious GN never called primary glomerulonephritis?
Because it is always secondary to infection
What is the prognosis of post-infectious GN?
95% of children recover with conservative treatment
40% of adults progress to chronic renal failure
What organisms cause post-infectious GN?
Group A beta-haemolytic Streptococcus
Non-streptococcal including bacterial, viral, and parastitic streptococcus
What is the most common cause of GN?
IgA nephropathy or Berger’s disease
What is the most common demographic for IgA nephropathy?
Young adults
What is the cause of IgA nephropathy?
Immune-complex mediated GN
How is IgA clinically presented?
Nephritic syndrome
Microscopic haematuria (blood picked up during tests)
Sometimes precipitated by Upper Respiratory Tract 1nfection (occurs at the same time as a sore throat unlike post-infectious GN)
Often presented while people are screening for health insurance
What does a light microscope show with IgA nephropathy?
Diffuse mesangial matrix expansion and hypercellularity (it is a mesangioproliferative GN)
What is seen on electron microscope and immunoflorescence for IgA nephropathy?
Granular mesangial IgA
Mesangial immune-complex deposits
What are secondary causes of IgA nephropathy?
Drugs
Infectious
Hepatobiliary, GI, rheumatological diseases and malignancy
What is the prognosis for IgA nephropathy?
33% resolve spontaneously
33% stable
33% progress to secondary FSGS/CRF
What is crescentic GN?
Pathological correlate to clinical presentation of rapidly progressive GN
It is a nephritic syndrome with rapid and severe rise in serum urea/creatinine
Can crescentic GN be an endpoint for diagnosis?
No the cause of it must be identified
What is the consequence of not treating crescenting GN?
It is a medical emergency. Chronic renal failure will occur within weeks to months if not treated.
What is the histological hallmark of crescentic GN?
Filling and occlusion of bowman’s space by proliferation of epithelial cells.
Due to rupture of capillary loops and bleeding into the bowman’s space so no urine can be produced
What are the types of crescentic GN?
Type 1 (anti-glomerular basement membrane disease) (20%)
Type 2 (Immune-complex mediated GN) (25%)
Type 3 (Paci-immune GN) (55%)
What is antiGBM disease?
Autoantibodies for alpha 3 chain of type IV collagen are produced
What is pulmonary-renal syndrome / goodpasture syndrome?
Autoantibodies may cross-react with Basement Membrane of pulmonary alveolar capillaries and cause a condition known as pulmonary-renal syndrome / goodpasture syndrome
What does crescentic GN look like on microscopy?
Light microscopy shows crescents with necrosis
Immunoflorescence shows linear capillary loop IgG
Electron microscopy shows no immune complexes because its too small to see (IgG target individual molecules)
What is lupus a secondary cause of?
Lupus can effectively reproduce all GN types that were discussed.
What is Pauci-immune GN?
Anti-neutrophil cytoplasmic antibody associated with GN and vasculitis
Autoantibodies are produced against cytoplasmic enzymes in neutrophils
What condition is pauci-immune GN associated with?
Associated with systemic small vessel vasculitis
What is pauci-immune GN also known as?
Anti-neutrophil Cytoplasmic antibody associated GN/Vasculitis (ANCA)
What is Wegner’s granulomatosis?
Triad of necrotising granulomatous inflammation of upper and lower respiratory tract and kidney
What is Churg-Strauss syndrome?
Similar to WG but with asthma and peripheral eosinophilia
What does Pauci-immune GN look like on light microscopy?
Crescents and granulomatous inflammation in WG
Eosinophil rich granuloma in CSS
