Nephrotic and Nephritic kidney disease Flashcards
What are the 5 main features of nephrotic syndrome?
- Proteinuria >3- 3.5g/day
- Hypoalbuminaemia <30g/dL
- Oedema
- Raised cholesterol
(hyperlipidaemia) - hypercoagulable state
What is the general cause of nephrotic syndrome?
structural changes in the glomeruli in response to glomerular injury causing excessive leakage of key plasma molecules including albumin.
This leads to the typical features of heavy proteinuria and hypoalbuminaemia.
Why are patients with nephrotic syndrome at increased risk of infections?
loss of immunoglobins from the glomerulus
Why does nephrotic syndrome present with Hyperlipidaemia?
due to a loss of oncotic pressure, which leads to elevated levels of cholesterol, low-density lipoprotein and triglycerides within the serum.
Increased hepatic lipogenesis due to low albumin and loss of oncoming pressure
a consequence of increased synthesis of lipoproteins (such as apolipoprotein B, C-III lipoprotein (a)), as a direct consequence of a low plasma albumin
Why do patients with nephrotic syndrome have a hypercoagulable state?
thought to be due to the loss of key anti-clotting factors such as anti-thrombin III, plasminogen, and protein C and S
Which conditions are known to cause nephrotic syndrome?
minimal change disease,
membranous glomerulopathy (nephropathy)
focal segmental glomerulosclerosis (FSGS)
Diabetic glomerulonephropathy
Amyloidosis
What is Minimal-change disease?
Immature differentiating CD34 stem cells appear to be responsible for the pathogenesis.
- most common in children, particularly boys
- Glomeruli appear normal on light microscopy
- Negative immunofluorescence
- On electron microscopy, fusion or effacement of the foot podocytes is seen, consistent with a disrupted podocyte actin cytoskeleton
In which population is Focal segmental glomerulosclerosis most common in?
African American
Hispanic
Which conditions is Focal segmental glomerulosclerosis commonly associated with? (2)
Sickle cell disease
HIV
In the histological images for Focal segmental glomerulosclerosis, what will you most likely see?
Effacement of food podocytes
Hyalinosis and segmental sclerosis
Non specific IgM, C1 or C3 deposition in the mesangial matrix
Describe what is primary and secondary membranous nephropathy
Primary - Autoimmune -
Antibodies to phospholipase A1 (anti-PLA2R)
Secondary
- Infection (Hep C, Hep B. HIV, Malaria, syphilis, sarcoidosis)
- Autoimmune (SLE / lupus nephritis)
- Medications (NSAIDS, Penicillamine, Gold, Anti- TNF)
- Malignancy
-
What would the histology of membranous nephropathy look like?
Spike and dome appearance of subendothelial deposits
Thickened basement membrane and capillaries
Describe the pathophysiology of Diabetic glomerulonephropathy?
Non enzymatic glycosylation of the vascular basement membrane leading to hyaline arteriosclerosis in kidneys.
This causes hyperfiltration at the efferent arterioles and microalbuminuria
What would the histology of Diabetic glomerulonephropathy look like?
Mesangial sclerosis
Kimmelstiel wilson nodules
which is —- Sclerotic eosinophilic nodules with a central acellular region
In the context of Systemic amyloidosis and its effect on the kidneys, which conditions is it associated with? (3)
Tb, Multiple myeloma, Rheumatoid arthritis
In amyloidosis there are 2 main proteins associated with 2 main pathologies, what are they and which pathologies are they associated with?
AA protein - Chronic inflammation
AL- multiple myeloma
What would the histology of amyloidosis look like?
Apple green birefringence under polarized light
Describe the 2 ways in which proteinuria is assessed?
Urine dip stick
25 hour urine collection (gold standard)
What are the 2 underlying mechanisms causing oedema in nephrotic syndrome?
Underfill hypothesis-
Decrease in intravascular colloid osmotic pressure due to low serum albumin
Intravascular volume depletion due to Movement of water from vascular space
into the interstitium
Activation of the renin angiotensin system and retention of salt and water
Overfill hypothesis
Primary sodium retention
Increased Na-K ATP pump in the collecting tubule
List the indications/ symptoms of nephritic syndrome
Early
- Urine Dip blood/ mild protein present
- Red cell cast on urine microscopy
Aggressive High Bp Mild oedema Urine Dip blood/ mild protein present Azotaemia (High BUN and creatinine) Oliguria - AKI
In the context of nephritic syndrome, when the urine dip comes back positive for blood and protein, which tests should be done next?
send for cytoloy( to look for
red cell casts) and culture (to rule out
infection)
Describe what post streptococcal glomerulonephritis is?
Usually occurs in childrne 2-4 weeks after group A beta haemolytic strep infection
List the causes of nephritic syndrome
Autoimmune/Immune mediated Small vessel vasculitis e.g ANCA associated vasculitis SLE Anti-GBM disease[Goodpastures] IgA nephropathy Cryoglobulinaemia
Infections
Viral- Hepatitis C, Hepatitis B, HIV
Post streptococcal
Subacute bacterial endocarditis
Malignancies
Lymphoma
Multiple Myeloma
Describe what post streptococcal glomerulonephritis is?
Usually occurs in childrne 2-4 weeks after group A beta haemolytic strep infection
Its a type 2 hypersensitivity reaction
Antistreptococcal antibodies are formed (ASO)
There will be low C3 levels
What does post streptococcal glomerulonephritis look like on histology/ cytology?
Elarged hypercellular glomeruli
Lumpy bumpy, granular, starry sky appearance
Subepithelial humps
Describe what rapidly progressive glomerulonephritis is?
- Refers to rapid progression of kidney disease (days- weeks)
Composed of multiple kidney conditions
- Good pastures syndrome (Anti-GBM disease)
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
- glomerulonephritis
Subtyped is determined base on immunofluorescence
Describe the immunofluorescence staining features for each type of rapidly progressive glomerulonephritis
- Good pastures syndrome
Linear IgG deposition on immunofluorescence staining - Granulomatosis with polyangiitis - negative/ pauci immune, weak / absent staining
- Microscopic polyangiitis
negative/ pauci immune, weak / absent staining - Diffuse proliferative glomerulonephritis
Granular staining
Which histological/ cytological feature is present for all rapidly progressive glomerulonephritis conditions?
Fibrin or macrophage based crescentic expansion
Crescent formation in bowman’s capsule
What is good pastures disease?
Type 2 hypersensitivity reaction
There are anti GBM and anti alveolar antibodies
Antibodies against type 4 collagen are formed (found in basement membrane and alveoli)
Symptoms -
kidney- haematuria
lungs - haemoptysis, SOB, Lung disease occurs before kidney disease by days to weeks
Describe what granulomatosis with polyangiitis (Wegeners) is?
Small and medium sized systemic vasculitis
Positive for PR3- ANCA and C-ANCA
Symptoms -
Kidney - haematuria
Lungs - haemoptysis, cough
Nasal rhinosinusitis (nasal obstruction, discharge or bleed)
- Sinusitis
- Otitis media and deafness
Eyes - Proptosis, diplopia, Loss of vision
CXR - Nodules +/- fluffy infiltrates or pulmonary haemorrhage
CT - Caviation +/- diffuse alveolar haemorrhage
Describe what Microscopic polyangiitis is?
Small vessel necrotising vasculitis
Similar to granulomatosis with polyangiitis just with no nasopharyngeal involvement and no granuloma formation
Associated with p-ANCA and MPO- ANCA
Describe what diffuse proliferative glomerulonephritis is?
What would be seen on histology/ cytology?
Associated with SLE (lupus)
Thickening of glomerular capillaries - WIRE LOOPS
Describe what IgA nephropathy is?
Symptoms -
Asymptomatic microhaematuria following GI/Respiratory infection
High serum IgA
Normal C3 levels
Which histological/ cytological feature is present for IgA nephropathy?
Mesangial IgA deposition
Mesangial proliferation
Describe what Membranoproliferative glomerulonephritis is?
Associated with hepatitis B and Hepatitis C
Tyoe 1- immunoglobulin mediated and associated with SLE (lupus)
Tyoe 2 complement mediated
Both types cause a decrease in C3
Both associated with intravenous drug abuse
What is the mechanism of glomerular inflammation?
Immunoglobulin mediated
Deposition of antibodies ( IgA, Anti GBM antibodies, immunecomplexes)
Activation of the complement pathway
Release of chemokines
Recruitment of leukocytes- Neutrophils, Macrophages, Lymphocytes
Further release of chemokines and cytokines
Glomerular inflammation, necrosis and crescent formation
Which tests are present on a nephritic screen?
Complements- C3/C4
Anti-streptolysin O titres
Immunoglobulins- IgG, IgM, IgA
ANA, anti ds-DNA
Serum Electrophoresis
Hepatitis C, Hepatitis B, HIV
ANCA
GBM antibody
Cryoglobulins
A false positive ANCA test can be caused by what?
infections e.g. Endocarditis
In the diagnostic work up for nephritic syndrome which test should be done in which order
Urine dip (look for protein and urine)
Urine analysis (microscopy) - Will see red cell cast in nephritic syndrome
Urine culture- look for an infective agent
Conduct sputum and blood cultures if indicated
Conduct chest X ray if indicated
Complete normal blooods (FBC, U and E ect)
Conduct a nephritic screen
Conduct a renal biopsy
What does the term ANCA stand for. Which aspects must be investigated when conducting a diagnostic work uo?
Anti-Neutrophil Cytoplasmic Antibodies
Immunofluorescence of leukocytes
– Two types
– Cytoplasmic [cANCA]
– Perinuclear [pANCA]
These are antibodies against parts of neutrophils and monocytes
ELISA using purified antigens
– Proteinase 3 [PR3] targeted by cANCA
– Myeloperoxidase [MPO] targeted by pANCA
Disease Associations – Small vessel vasculitis • Wegeners[cANCA], Microscopic polyangitis [pANCA] • Churg- Strauss – Drug Induced vasculitis
What can cause a low C3 and C4 with renal biopsy?
SLE
MesangioCapillary GN [MCGN] associated with hepatitis C
Cryoglobulinaemia
Post streptococcal GN
Infective endocarditis
Foreign bodies- e.g.- shunt nephritis
Cholesterol emboli
