Histopathology 13 - Histopathology of Systemic Disease Flashcards
What can John cunningham virus infection in HIV positive patients lead to?
Progressive multifocal leukoencephalopathy
What is the most common opportunistic infection in HIV positive patients?
CMV
Which herpes virus causes kaposi sarcoma?
HHV8
What is the main histological finding in sarcoidosis?
Non-caseating granulomas
How does end-stage sarcoidosis appear on CXR?
‘Honeycomb’ lung
What is a granuloma made up of?
Lymphoid cells and giant cells
- GRANULOMA- organised collection of activated epithelioid macrophages
- Giant cells- formed by the fusion of macrophages
- outside of granulomas, there will be lymphocytes
What colour does IgG4 stain when positive?
Brown
Recall 3 diseases caused by IgG4 inflammation
Riedel thyroiditis
Autoimmune pancreatitis
Inflammatory pseudotumours
others;
Billiary obstruction
retroperitoneal fibrosis
What is the structure of amyloid?
Beta pleated sheet that forms non-branching fibrils
What is the cause of AA amyloidosis?
Chronic inflammation
Which conditions are particularly implicated in the development of AA amyloidosis?
Crohn’s
Rheumatoid arthritis
What conditions can cause AL amyloidosis?
Myeloma
B cell neoplasms
**not MGUS and smouldering
What is the link between transthyretin and amyloidosis?
Transthyretin mutation can –> cardiac amyloid
What stain can be used for amyloid?
Congo red - gives green birefringence under polarised light
Where does CMV cause infection in HIV positvie patients?
CMV oesophagitis
Classical finding of CMV oesophagitis
Causes osopahgeal ulcers
Histopathological findings of CMV infection
CMV oeosphagitis - causes ulcers
Epithelial cells and coin like nuclear inclusions in nucleus (CMV inclusion)
Stains brown in immunohistochemistry
Which tumours do HIV positive patients get?
- Kaposi’s sarcoma
- Lymphoma - especially B cell lymphoma
EBV–> Burkitt’s lymphoma
- others:
- HPV
- Often high-risk variants 16 and 18
What CNS disease do HIV positvie patients get?
- Progressive encephalopathy - AIDS dementia complex
- Encephaitis/meningitis - opportunistic infections
- CNS lymphoma
Histology of Kaposi’s sacrcoma
- elevated purple, pink, brown bumps on skin or in mouth and/or throat.
- The mass is made up of spindle shaped cells with lots of space between them
- Stained for HHV8 which is a marker for Kaposi’s sarcoma
Histology of CNS lymphoma
Tumour mass (pinky area of the brain slice) - rather than as disseminated disease which is usually the case
Perivascular lymphomatous infiltrate
Histopathology of myobacterial disease
- caseating cheesy granulomas - collection of activated macrophages with. necrotic core
- often seen in apices of the lungs
- acid fast bacilli on ziehl neelson stain
Where do myobacterial diseases infect?
- Lung
- Lymph node: Disc damage and collapse
- Bone- vertebra
- Heart e.g. pericarditis
- Calcifying pericarditis- almost always due to TB
- GIT e.g. peritonitis
- CNS: e.g. meningitis
Features of mycobacterial disease in the lungs
- miliary TB
- Cavitating lesions
Sarcoid: pathology
- non-caseating grnaulomas
- diagnosis of exlcusion - after TB has been excluded
characteristic of sarcoid is granulomas- they are firm and solid (no caseating centre)
What is pathognemonic of granulomas?
Epithelioid macrophages
collection of activated macrophages
May see giant cells (langherhans cells) and lymphoid cells around the epithelioid macrophages
Clinical features of sarcoidosis
bilateral hilar lymphadenopathy
hypercalcaemia:
What is IgG4 related disease?
- Inflammation dominated by plasma cells that make IgG4 antibody
- Causes fibrosis and obliteration of veins → destruction of tissue
- It is an inflammatory response but NOT infection
Examples of IgG4 related disease
5 stages of liver disease
- fatty liver hepatitis (steatohepatitis) – progressive inflammation characterised by neutrophils, ballooning- Mallory Denk bodies, fibrosis
Most common cause if cirrhosis in the UK
NAFLD
Diseases caused by alcohol in GI tract
- acute gastritis
- oesophageal varices
Alcohol effects on neurological system
- peripheral neuropathy
- wenircke’s encephalopathy
- Wernicke-Korsakoff syndrome
effect of alcohol in CVS
- dilated cardiomyopathy
- hypertension
- vascular disease - ATHEROMA:
- NB some studies show moderate intake of wine can reduce risk of atherosclerosis
effect of alcohol in pancreas
- acute pancreatitis
- chronic pancreatitis
effect of alcohol on foetus
foetal alcohol syndrome
- FIRST TRIMESTER increases risks to mother: miscarriage, still birth, prematurity
- Alcohol use after first trimester increases risk of abnormalities to foetus and developmental abnormalities growing up:
- Microcephaly
- Cardiac abnormalities- pan systolic murmur
- Short palpebral fissures- small eye folds
- Hypoplastic upper lip- thin
- Learning disability
- Absent philtrum
- Reduced IQ
- thin vermillion
alcohol and cancer
- oral cavity
- pharynx and oeosphagus
- liver
- breast cancer
Effect of cystic fibrosis on pancreas
- duct obstruction by thick mucuous secretions
- exocrine atrophy - inability to produce lipase, protease, amylase >>> maldigestion and malabsorption
this then leads to endocrine atrophy + chronic pancreatitis
effect of cystic fibrosis on salivary glands
- duct obstruction
- atrophy
effect of cystic fibrosis on intestine
meconium ileus - infants
Distal Intestinal Obstruction Syndrome (DIOS
effect of cystic fibrosis on liver
- biliary obstruction >> progressive billiary cirrhosis
- hepatic steatosis
all of this can cause portal hypertension + cirrhosis
effect of cystic fibrosis on lung
- broncial obstruction
- superimposed infection with abscess formation
- bronchiectasis
effect of cystic fibrosis on male genital tract
infertility
organisms associated iwth abscess formation in cystic fibrosis
Staph aureus
Haemophilus influenzae
psuedomonas
What component does amyloid contain?
P- component
What structure does amyloid protein have?
Beta pleated with non branching fibrils
Two main types of amyloid
AA: from serum amyloid A protein (Acute phase protein synthesised by the liver)
- produced in inflammatory conditions
AL: Also known as primary amyloidosis
- derived from light chains on immunoglobulins
- classically in multiple myeloma or b cell lymphoma
Where is serum amyloid protein produced?
Liver - it is an acute phase protein so it will be elevated in longstanding inflammatory disease
eg crohn’s disease, rheumatoid arthritis
Other minor causes of amyloid protein formation
- transthyretin - happens due to mutation >> predisposes to cardiac amyloid
- beta 2 macroglbulin - peritoneal dialysis patients
- alpha beta 2 protein - alzheimer’s disease
- insulin, calcitonin - endocrine tumours, , medullary carcinoma of thyroid
Staining for amyloid
Result under polarised light
Result on electron microscopy
Congo red dye then examine under polarised light
Apple green birefringence under polarised light
electron microscopy - fibrillar structure
Clinical features of amyloidosis
What does amyloidosis cause in kidneys?
- Proteinuria
- Renal failure
HIV: Opportunistic infections
- Pneumocystis jiroveci: pneumonia
- CMV: especially retina and GIT
- Retinitis
- Oesophageal ulcerations
- Candida
- Can become invasive rather than being superficial
- TB and atypical mycobacteria
- Cryptococcus: meningitis
- Toxoplasma gondii: encephalitis and mass lesions
- JC papovirus: progressive multifocal leukoencephalopathy
- HSV
- Cryptosporidium, Isospora belli, microsporidia: GIT
in IgG4 related disease is it polyclonal and monoclonal
Polyclonal (proliferation of plasma cells is polyclonal) NOT monoclonal but sub specific.
summarise alcoohl and its complications in different organ systems
summarise complications of CF
can amyloid be broken down my enzymatic degradation
- Resistant to enzymatic degradation
causes of granulamtous inflammation in the liver
TB, mycobacterial infections, sarcoid, Primary biliary cholangitis, drug induced disease, malignancy
