W19 - Systemic pathology

Question 1

HIV opportunistic infections - what does each cause? PART 1

• Pneumocystic jiroveci =>
• CMV =>
• Candida =>
• Tuberculosis and atypical mycobacteria =>
• Cryptococcus =>

Answer 1

HIV opportunistic infections - what does each cause?

• Pneumocystic jiroveci => pneumonia
• CMV => retinitis, GIT (eosophagitis)
• Candida => oesophageal candidiasis, candidaemia
• Tuberculosis and atypical mycobacteria => pulmonary TB
• Cryptococcus => meningitis

Question 2

HIV opportunistic infections - what does each cause? PART 2

• toxoplasma gondii =>
• JC papovavirus =>
• Herpes simplex =>
• Cryptospordium, isospora belli, microsporidia =>

Answer 2

HIV opportunistic infections - what does each cause?

• toxoplasma gondii => encephalitis and mass lesions
• JC papovavirus => progressive multifocal leukoencephalopathy
• Herpes simplex => HHV-8 (Kaposi’s sarcoma)
• Cryptospordium, isospora belli, microsporidia => GIT

Question 3

mycobacteria causes _______ granulomas

sarcoid causes ________ granulomas

Answer 3

mycobacteria causes caseating granulomas

sarcoid causes non-caseating granulomas

Question 4

What is the likely pathology? Explain findings of gross specimen and histo slide

Answer 4

mycobacterial infection

Gross specimen = cavitations in R upper lobe (most common area for TB infection)

histology slide = granuloma with caseaous necrosis (cheese-like cell death - most commonly associated with TB infection)

Question 6

Granulomas in sarcoid are _______

Describe the cells in the core and peripehery of a sarcoid granuloma

Answer 6

Granulomas in sarcoid are non-caseating granulomas

Central area contains epitheloid cells, giant cells, and macrophages.

Peripheral area contains lymphocytes

Question 7

Sarcoid - how to diagnose it?

Answer 7

Sarcoid is a diagnosis of exclusion as it does not have any specific tests. Must rule out all other differential diagnoses

Question 9

IgG4 related disease - condition per system affected:

• Salivary and lacrimal glands =>
• thyroid gland =>
• Peritoneum =>
• Liver =>
• Pancreas =>
• Mass lesions =>

Answer 9

IgG4 related disease - condition per system affected:

• Salivary and lacrimal glands => Mikulicz syndrome
• thyroid gland => Reidel thyroiditis
• Peritoneum => Retroperitoneal fibrosis
• Liver => Biliary obstruction
• Pancreas => Autoimmune pancreatitis
• Mass lesions => Inflammatory pseudotumour

Question 10

Describe what IgG4 related disease is

Answer 10

It is a non-infectious inflammatory disease in which inflamation is dominated by IgG4 abs produced by plasma cells

Question 11

What is the pathophysiology of IgG4 related disease?

Answer 11

Excessive IgG4 ab production and infiltration into tissues => causing fibrosis and obliteration of veins

Question 13

Alcoholic systemic disease - describe conditions per system affected:

• Liver =>
• GI tract =>
• Nervous system =>
• Cardiovascular system =>
• Pancreas =>
• Foetus =>
• Cancer =>

Answer 13

Alcohol as causing systemic disease - describe conditions per system affected:

• Liver => steatosis, steatohepatitis, cirrhosis, hepatocellular carcinoma
• GI tract => acute gastritis, oesophageal varices
• Nervous system => Peripheral neuropathy, Wernicke-Korsakoff Syndrome
• Cardiovascular system => Dilated cardiomyopathy, Hypertension, atheroma (and may decrease it - remember red wine)
• Pancreas => Acute/chronic pancreatitis
• Foetus => foetal alcohol syndrome
• Cancer => oral cavity, pharynx, oesophagus, liver, breast

Question 14

Cystic fibrosis as a genetic disease that affects multiple systems - describe effect on each system below:

• Pancreas =>
• Salivary glands =>
• Intestine =>
• Liver =>
• Lung =>
• Male genital tract =>

Answer 14

Cystic fibrosis as a genetic disease that affects multiple systems - describe effect on each system below:

• Pancreas => Duct obstruction, exocrine atrophy
• Salivary glands => Duct obstruction, atrophy
• Intestine => Meconium ileus
• Liver => Biliary obstruction, cirrhosis
• Lung => Bronchial obstruction, superimposed infection with abscess formation (i.e. Staph a., haemophilus influenzae, pseudomonas)
• Male genital tract => Infertility, absence of the vas

Question 15

Amyloidosis - describe what this condition is

Answer 15

Amyloidosis is the deposition of an abnormal proteinaceous substance in non-branching fibrils in various organs

Question 16

The proteins in amyloidosis are non-resistant/resistant to enzymatic degradation?

Answer 16

The proteins in amyloidosis are RESISTANT to enzymatic degradation

Question 17

The proteins in amyloidosis are in what structural format - alpha helix or beta pleated sheets?

Answer 17

Beta pleated sheets

Question 18

Amyloid - Classification I

Name the classes

Answer 18

Amyloid - Clasification I

AA - derived from serum amyloid A

=> i.e. Crohn’s Disease, Rheumatoid arthritis

AL - derived from light chains

=> i.e. multiple myeloma, B cell lymphoma

Question 19

Who is at increased risk of developing AA amyloidosis? Name 2 conditions

Answer 19

Crohn’s disease, rheumatoid arthritis

Question 20

Who is at increased risk of developing AL amyloidosis? Name 2 conditions

Answer 20

Multiple myeloma (MM), B cell lymphoma

Question 21

H&E slide of kidney - what does it show? What staining would you do next?

Answer 21

thickened vascular walls => protein deposition?

Stain with Congo Red for amyloidosis

Question 22

Kidney histo slide stained with congo red - what disease is likely present?

Answer 22

Amyloidosis

Question 23

There are certain proteins that can arise in certain conditions, giving rise to amyloidosis.

Name the protein associated with each of the following:

• Mutational =>
• Peritoneal dialysis =>
• Alzheimer’s =>
• Endocrine tumours =>

Answer 23

• Mutational => transthyretin
• Peritoneal dialysis => beta2-macroglobulin
• Alzheimer’s => Beta2 protein
• Endocrine tumours => insulin, calcitonin

Question 24

Amyloid staining:

• dye =>
• Under polarised light =>

Answer 24

Amyloid staining:

• dye => Congo red
• Under polarised light => Apple green birefringence

Question 25

Amyloidosis - clinical features:

• Renal =>
• Cardiovascular =>
• CNS =>
• Rheumatological =>
• Haematological =>
• Elsewhere =>

Answer 25

Amyloidosis - clinical features:

• Renal => proteinuria, nephrotic syndrome, renal failure
• Cardiovascular => restrictive cardiomyopathy, arrhythmias
• CNS => Autonomic neuropathy
• Rheumatological => Carpal tunnel syndrome
• Haematological => Bleeding on injury, macroglossia
• Elsewhere => depositions in blood vessels, endocrine organs, liver, spleen