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MET3B -Renal > Nephrotic and Nephritic kidney disease > Flashcards

Nephrotic and Nephritic kidney disease Flashcards

1
Q

What are the 5 main features of nephrotic syndrome?

A
  • Proteinuria >3- 3.5g/day
  • Hypoalbuminaemia <30g/dL
  • Oedema
  • Raised cholesterol
    (hyperlipidaemia)
  • hypercoagulable state
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2
Q

What is the general cause of nephrotic syndrome?

A

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.

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3
Q

Why are patients with nephrotic syndrome at increased risk of infections?

A

loss of immunoglobins from the glomerulus

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4
Q

Why does nephrotic syndrome present with Hyperlipidaemia?

A

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

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5
Q

Why do patients with nephrotic syndrome have a hypercoagulable state?

A

thought to be due to the loss of key anti-clotting factors such as anti-thrombin III, plasminogen, and protein C and S

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6
Q

Which conditions are known to cause nephrotic syndrome?

A

minimal change disease,

membranous glomerulopathy (nephropathy)

focal segmental glomerulosclerosis (FSGS)

Diabetic glomerulonephropathy

Amyloidosis

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7
Q

What is Minimal-change disease?

A

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
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8
Q

In which population is Focal segmental glomerulosclerosis most common in?

A

African American

Hispanic

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9
Q

Which conditions is Focal segmental glomerulosclerosis commonly associated with? (2)

A

Sickle cell disease

HIV

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10
Q

In the histological images for Focal segmental glomerulosclerosis, what will you most likely see?

A

Effacement of food podocytes

Hyalinosis and segmental sclerosis

Non specific IgM, C1 or C3 deposition in the mesangial matrix

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11
Q

Describe what is primary and secondary membranous nephropathy

A

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
-

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12
Q

What would the histology of membranous nephropathy look like?

A

Spike and dome appearance of subendothelial deposits

Thickened basement membrane and capillaries

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13
Q

Describe the pathophysiology of Diabetic glomerulonephropathy?

A

Non enzymatic glycosylation of the vascular basement membrane leading to hyaline arteriosclerosis in kidneys.

This causes hyperfiltration at the efferent arterioles and microalbuminuria

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14
Q

What would the histology of Diabetic glomerulonephropathy look like?

A

Mesangial sclerosis

Kimmelstiel wilson nodules

which is —- Sclerotic eosinophilic nodules with a central acellular region

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15
Q

In the context of Systemic amyloidosis and its effect on the kidneys, which conditions is it associated with? (3)

A

Tb, Multiple myeloma, Rheumatoid arthritis

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16
Q

In amyloidosis there are 2 main proteins associated with 2 main pathologies, what are they and which pathologies are they associated with?

A

AA protein - Chronic inflammation

AL- multiple myeloma

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17
Q

What would the histology of amyloidosis look like?

A

Apple green birefringence under polarized light

18
Q

Describe the 2 ways in which proteinuria is assessed?

A

Urine dip stick

25 hour urine collection (gold standard)

19
Q

What are the 2 underlying mechanisms causing oedema in nephrotic syndrome?

A

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

20
Q

List the indications/ symptoms of nephritic syndrome

A

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
21
Q

In the context of nephritic syndrome, when the urine dip comes back positive for blood and protein, which tests should be done next?

A

send for cytoloy( to look for
red cell casts) and culture (to rule out
infection)

22
Q

Describe what post streptococcal glomerulonephritis is?

A

Usually occurs in childrne 2-4 weeks after group A beta haemolytic strep infection

23
Q

List the causes of nephritic syndrome

A 
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

24
Q

Describe what post streptococcal glomerulonephritis is?

A

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

25
Q

What does post streptococcal glomerulonephritis look like on histology/ cytology?

A

Elarged hypercellular glomeruli

Lumpy bumpy, granular, starry sky appearance

Subepithelial humps

26
Q

Describe what rapidly progressive glomerulonephritis is?

A
  • 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

27
Q

Describe the immunofluorescence staining features for each type of rapidly progressive glomerulonephritis

A
  • 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
28
Q

Which histological/ cytological feature is present for all rapidly progressive glomerulonephritis conditions?

A

Fibrin or macrophage based crescentic expansion

Crescent formation in bowman’s capsule

29
Q

What is good pastures disease?

A

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

30
Q

Describe what granulomatosis with polyangiitis (Wegeners) is?

A

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

31
Q

Describe what Microscopic polyangiitis is?

A

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

32
Q

Describe what diffuse proliferative glomerulonephritis is?

What would be seen on histology/ cytology?

A

Associated with SLE (lupus)

Thickening of glomerular capillaries - WIRE LOOPS

33
Q

Describe what IgA nephropathy is?

A

Symptoms -
Asymptomatic microhaematuria following GI/Respiratory infection

High serum IgA
Normal C3 levels

34
Q

Which histological/ cytological feature is present for IgA nephropathy?

A

Mesangial IgA deposition

Mesangial proliferation

35
Q

Describe what Membranoproliferative glomerulonephritis is?

A

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

36
Q

What is the mechanism of glomerular inflammation?

A

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

37
Q

Which tests are present on a nephritic screen?

A

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

38
Q

A false positive ANCA test can be caused by what?

A

infections e.g. Endocarditis

39
Q

In the diagnostic work up for nephritic syndrome which test should be done in which order

A

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

40
Q

What does the term ANCA stand for. Which aspects must be investigated when conducting a diagnostic work uo?

A

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
41
Q

What can cause a low C3 and C4 with renal biopsy?

A

SLE

MesangioCapillary GN [MCGN] associated with hepatitis C

Cryoglobulinaemia

Post streptococcal GN

Infective endocarditis

Foreign bodies- e.g.- shunt nephritis

Cholesterol emboli

MET3B -Renal (5 decks)

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