Histopathology Flashcards
What locations are most at risk of atherosclerotic plaque formation?
Locations with turbulent flow: Coronary arteries AA Carotid arteries Iliac arteries
What are the components of an atherosclerotic plaque?
Cellular: SMC, macrophages
Extra cellular membrane
Lipids
What are non-modifiable risk factors for atherosclerosis?
Age: 5x incr risk >60 yrs
Male
FHx
Genetic risk ?
What are modifiable risk factors for atherosclerosis?
HTN: incr risk by 60%
T2DM
Smoking
Hyperlipidaemia
What is the process of atherosclerosis ?
Fatty streaks + RF -> atheroma formation
Endothelial dysfunction -> subintimal LDL accumulation
LDL modification + oxidation -> inflammation -> monocyte adhesion
Monocyte -> intima = macrophage -> takes up ox/mod LDL= foam cell
Apoptosis of foam cells -> incr inflammation -> incr adhesion mols -> incr macrophage recruitment
Intimal SM cell recruitment -> fibrous cap
What are the risk factors for mortality with MI?
Incr age
Female
DM
Previous MI
What are the histological changes which occur following an MI?
Secs: reversible loss of contractility
20-30 mins: irreversible loss of contractility
What occurs when the myocardium is starved of oxygen and nutrients in infarction?
60s: potentially reversible loss of contractility - acute HF
20-30 mins: irreversible loss of contractility
What are immediate complications of MI?
40%
Cardiogenic shock: due to contractile dysfunction = mortality 70%
What are acute complications of MI?
Hours: fatal arrhythmia e.g. VF, or VT
Days: papillary muscle rupture -> mitral regurg
Day 2-3: transmural infarct -> acute pericarditis
Day 3-7: cardiac rupture: ventricular wall-> haemopericardium, septum -> L>R shunt
What are chronic complications of MI?
> 1 wk: mural thrombus, ventricular aneurysm, PE
Wks- months: Dresslers pericarditis
Months-yrs: chronic HF
What are the symptoms of Left HF?
Dyspnoea
Orthopnoea
PND
What are the symptoms of Right HF?
Peripheral oedema
Ascites
Facial engorgement
What are the causes of heart failure?
Ischaemic heart disease Valve disease HTN Myocarditis Cardiomyopathy Arrhythmias
What are the complications of heart failure?
Sudden death Arrhythmias Systemic emboli Pulmonary oedema Hepatic cirrhosis
What are the structural features of cardiac failure?
Dilated heart: scarring and thinning of walls
Microscopy shows scarring and replacement of myocardium
What is the process by which heart failure develops?
Systolic dysfunction -> physiological adaptation to maintain tissue perfusion
Reduced CO-> RAS -> Na + water retention = oedema
Reduced SV-> sympathetic NS prolonged -> incr TPR -> incr afterload
= dilation, hypertrophy, myocardial fibrosis
What are causes of aneurysm formation?
Congenital incl: Marcans
Atherosclerosis
HTN
What is angina pectoris?
Transient ischaemia of myocardium Stable: seen on exertion, relieved by rest, no plaque disruption Seen with 75% stenosis Unstable: occurs at rest Seen with 90% stenosis
What is prinzmetal angina?
Uncommon
Chest pain at rest
Due to coronary artery vasospasm
Unknown aetiology
What are the features of sudden cardiac death?
Background of IHD + lethal arrhythmia
50% plaque rupture, 25% MI changes
Electrical instability at sites distant from conduction system, near scars from old ?MI
What makes plaques vulnerable in atherosclerosis?
Lots of foam cells Thin fibrous cap Few SM cells Clusters of inflammatory cells HTN
What are the features of hypertrophic cardiomyopathy?
Myocardial hypertrophy No ventricular dilatation Thick-walled, heavy, hyper-contracting Histo: myocyte disarray = arrhythmogenic AD: betaMHC, MYBP-C, Trop-T Sudden cardiac death 15-20% -> DCM
Dilated cardiomyopathy
Causes: idiopathic, alcohol, peripartum, genetic, sarcoidosis, haemochromatosis, myocarditis
Systolic dysfunction
Indirect dysfunction:
IHD, valvular heart disease, htn
Restrictive cardiomyopathy
Causes:
Sarcoidosis, amyloidosis, radiation induced fibrosis
Diastolic dysfunction
Indirect dysfunction: pericardial constriction
Hypertrophic cardiomyopathy
Causes: genetic, storage diseases
Diastolic dysfunction
Indirect dysfunction: HTN, AS
When does acute rheumatic fever occur and which systems are involved?
5-15 yrs
2-4 wks post strep throat infection
Cardiac: endo, myo and pericarditis
Joints: arthritis, synovitis
Skin: erythema marginatum, subcutaneous nodules
Neuro: encephalopathy, Sydenham’s chorea
Also: fever, tachycardia, malaise, migrating polyarthralgia
Why does acute rheumatic fever occur following strep throat infection and what are the histological features?
Lancefield gp A strep
Antigenic mimicry: cell mediated immunity and antibodies to strep cross react with myocardial antigens
Verrucae
Aschoff bodies: small giant cell granulomas
Anitschkov myocytes: regenerating myocytes
How is rheumatic fever diagnosed and treated?
Jones criteria
Plus raised ESR and ASOT
Benzylpenicillin
Or erythromycin if allergic
What are the features of rheumatic heart disease?
Small warty verrucae along valve leaflet lines of closure
Due to antigenic mimicry: cross reaction of anti strep antibodies and cardiac tissue
What are the features of infective endocarditis?
Large irregular masses on valve cusps extending into the chordea
Due to colonisation of valves or mural endocardium by microbes
What are the features of non-bacterial thrombotic endocarditis AKA marantic?
Small bland vegetations attached to lines of closure formed of fibrin
Due to hypercoagulable states
DIC
What type of endocarditis gives rise to small, warty, platelet rich, sterile vegetations?
Libman-Sachs
Assoc with SLE + antiphospholipid synd
What might cause a bacteraemia leading to infective endocarditis?
Poor dental hygiene: strep viridans
IVDU: staph aureas
Iatrogenic: central lines, surgery
What factors predispose to endocarditis?
Rheumatic heart disease
Valve disease: e.g. Mitral prolapse, calcified valves
Prosthetic valves
Congenital defects: bicuspid aortic valve
What organisms might cause acute endocarditis?
Staph aureas
Strep pyogenes
High virulence with large vegetations, spread to aorta
What organisms might cause subacute endocarditis?
Strep viridans Staph epidermis HACEK Coxiella Mycoplasma Candida Low virulence with small vegetations, spreads to chordae
What are the clinical features of endocarditis?
Fever, malaise, anaemia, rigors
Splenomeg, new murmur
Roth spots, splinter haemorrhages, janeway lesions, oslers nodes
How is endocarditis diagnosed and treated?
Dukes criteria: 2 maj + 1 min, 3 min + 1 maj or 5 min
Maj: +ve blood cultures, typical organism, evidence of endocard involv.
Min: fever, vasculitic phenomena, immune phenomena, predisposing heart condition/IVDU, micro or echo evidence not meeting maj criteria
Benzylpenicillin + gentamicin
What are the five types of pericarditis and their respective causes?
Fibrinous: MRI or uraemia Purulent: staphylococcus Granulomatous: TB Haemorrhagic: tumour, TB, uraemia Fibrous: any, e.g. Constrictive
What is a pericardial effusion and what can cause them?
Serous fluid in pericardial sac: due to chronic HF
Or
Exudative fluid: due to inflammation, infection, malignancy or AI
What valvular disease might you expect to see in a middle aged woman with SOB + chest pain?
Mid systolic click + late systolic murmur
Mitral valve prolapse
What valvular disease might you expect to see in an elderly man with a recent history of syncope?
Systolic murmur at upper right sternal border, with an ejection click
Aortic stenosis
What is the pathophysiology underlying acute asthma?
Allergen sensitisation
T cell activation
IgE release from plasma cells
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What is the Pathophysiology underlying chronic asthma?
SMC hyperplasia
Increased mucus production
WBC infiltrates
What histological features are seen in asthma?
Eosinophils
Curschmann spirals: shed epithelium
Charcot-Leyden crystals
What histological features are seen in chronic bronchitis?
Airway damage:
Airway dilation
Goblet cell hyperplasia
Mucous gland hypertrophy
What are the complications seen with chronic bronchitis?
Recurrent infection
Chronic hypoxia
Pulmonary htn
What are the histological features of centrilobular emphysema?
Parenchyma damage:
Air space enlargement
Wall destruction
Loss of alveolar parenchyma distal to terminal bronchiole
What complications are associated with centrilobular emphysema?
Pneumothorax - due to bullae
Respiratory failure
Pulmonary htn
What is the cause of pan acinar emphysema?
Alpha-1-antitrypsin deficiency
What are the features of bronchiectasis?
Permanent dilatation and scarring of the bronchi
Cough, purulent sputum + fever
Complications incl: recurrent infections, haemoptysis, pulmonary htn, amyloidosis
List some inflammatory causes of bronchiectasis
Post infection Post inflammation I.e. Aspiration Obstruction Asthma Ciliary dyskinesia Systemic disease Secondary to bronchiolar disease + interstitial fibrosis
What are congenital causes of bronchiectasis?
CF
Hypogammaglobulinaemia
Primary ciliary dyskinesia
What are the four categories of interstitial lung disease?
Fibrosing
Granulomatous
Eosinophilic
Smoking related
How might interstitial lung disease present?
SOB, end inspiratory crackles, cyanosis, pulmonary hypertension, cor pulmonale
Restrictive spirometry results
CXR: honeycomb features
What conditions are considered to be fibrosing type interstitial lung disease?
Idiopathic pulmonary fibrosis Pneumoconiosis Cryptogenic organising pneumonia Drug induced Radiation pneumonitis Assoc with connective tissue disease
What are the features of cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?
Exertional dyspnoea, non productive cough, cyanosis, pulm htn
Histology:
Progressive, patchy, interstitial fibrosis with loss of normal architecture and honeycomb change, beginning at lobule periphery
Treatment:
Steroids, cyclophosphamide, azathioprine
What are the features of pneumoconiosis?
Occupational lung disease
Non neoplastic reaction to inhaled inorganic particles
Affecting upper lobe
E.g. Silicosis, asbestosis
What are the histological features of a granuloma?
Collection of histiocytes, macrophages
With or without multinucelated giant cells
What are the features of extrinsic allergic alveolitis/hypersensitivity pneumonitis/ cryptogenic organising pneumonia/ bronchiolitis obliterans organising pneumonia ?
Immune mediated lung disorders
Due to prolonged/intense exposure to inhaled organic antigens
Causes widespread alveolar inflammation
Histology: Polypoid plugs of loose connective tissue within alveoli/bronchioles, granuloma formation, organising pneumonia
Acute: fever, chills, chest pain, SOB within hrs, settles over nxt day
Chronic: progressive, persistent, productive cough, SOB, clubbing, severe weight loss
Features of bronchopneumonia
Low virulence organisms
Elderly/COPD
Patchy peribronchial distribution (often lower lobes)
Features of lobar pneumonia?
High virulence organisms Young individuals Fibrinosuppurative consolidation: Red hepatisation: neutrophilia Grey hepatisation: fibrosis Resolution:
What is pulmonary hypertension?
Pulmonary pressure > 25 mmHg
What are causes of pulmonary hypertension?
Precapillary: vasoconstrictive or emboli
Capillary: pulmonary fibrosis
Post capillary: veno-occlusive disease or left HF
Features of pulmonary emboli
Large: Impact in main pulmonary arteries ->acute cor pulmonale, cardio genic shock, death if >60% occluded
Small: -> silent / peripheral wedge infarction, repeated infarction -> pulm htn
What are the histological features of pulmonary oedema?
Intra alveolar fluid
Iron laden macrophages
Diffuse alveolar damage
Causes of acute respiratory distress syndrome in adults?
Infection
Trauma incl burns
Aspiration
What are the histological features of rapid onset respiratory failure?
Expanded lungs:
firm
airless
plum coloured
Which lung cancers are most associated with smoking?
Small cell
Squamous cell
Which lung cancer is commonest in non smokers?
Adenocarcinoma
What are the pathological and histological features of squamous cell carcinoma of the lung?
Path: proximal bronchi, local spread, late mets, less chemosensitive
Histo: keratinisation, intercellular prickles
Assoc with: cavitation + hypercalcaemia
Subtypes incl: papillary, basaloid
What are the pathological and histological features of adenocarcinoma of the lung?
Path: peripheral epithelial tumour w. glandular differentiation or mucin production, metastasises early, EGFR mutations
Histo: glandular differentiation
Cyto: mucin vacuole containing cells
What are the pathological and histological features of large cell carcinoma of the lung?
Path: poorly differentiated epithelial tumour
Large cells, large nuclei,mprominent nucleoli
Histo: no evidence of glandular or squamous differentiation
Poor prognosis
What are the pathological and histological features of small cell carcinoma of the lung?
Path: central, proximal bronchi, neuro endocrine cells
V malignant, early mets -> bone, brain, liver, adrenal, 1 yr
Ectopic ACTH, Lambert Eaton, cerebellar degeneration
P53 + RB1 mutations common
Histo: small, undifferentiated, hyperchromatic, oat cells
Molecular markers in lung cancer:
ERCC1
Poor response to cisplatin
Molecular markers in lung cancer:
EGFR
Usually seen in adenocarcinoma
Good response to TKI
Molecular markers in lung cancer:
Kras
Seen in adeno/squamous carcinoma
No response to TKI
Poor prognosis
Molecular markers in lung cancer:
EML4-ALK
Usually adenocarcinoma
No benefit from TKI
Complications seen in lung cancer
Bronchial obstruction -> haemoptysis, pneumothorax
Pleural/pericardial invasion -> effusions, tamponade
Mediastinal invasion -> SVC syndrome
Oesophageal invasion -> dysphasia
Chest wall invasion -> pleuritic pain
Nerve invasion -> hoarse voice, horner’s
Paraneoplastic syndromes: SIADH, Lambert Eaton, Cushing’s (HPT with squamous)
What is the z line in the oesophagus?
Another name for squamo-columnar junction
Betw proximal 2/3 squamous epithelium
And distal 1/3 columnar epithelium
What are complications of reflux oesophagitis?
Ulceration Haemorrhage Barret's oesophagus Stricture Perforation
What is Barret’s oesophagus?
Intestinal metaplasia of squamous mucosa = columnar epithelium with goblet cells
In whom is oesophageal adenocarcinoma usually seen and what are the risk factors?
White men
Assoc with Barrett’s oesophagus
RF: smoking, obesity, prev radiation therapy
In whom is squamous cell oesophageal carcinoma usually seen and what are the risk factors?
Afro Carribean men
RF: ETOH, smoking, achalasia, nutritional deficiencies, nitrosamines, HPV, Plummer Vinsent
What are the pathological and histological features of squamous cell oesophageal carcinoma?
Presents with: progressive dysphagia, odynophagia, anorexia, weight loss
Path: rapid growth, early spread -> LNs, liver
50% mid 1/3, 30% lower 1/3, 20% upper 1/3
What are the pathological features of acute gastritis?
Neutrophil infiltrate
Following insult
E.g. Aspirin, NSAIDs, alcohol, corrosives, acute H.pylori
What are the pathological features of chronic gastritis?
Lymphocytic infiltrate
Following H.pylori insult
(Or: CMV, HIV, HSV, AI, ETOH, smoking)
Complications incl: gastric ulceration or meta -> dysplasia
What are the pathological and histological features of gastric ulcers?
Epigastric pain +- weight loss
Breach of muscularis mucosa= exposed submucosa
Punched out lesion with rolled margins
Complications incl: IDA, perforation, malignancy
What are the pathological features of gastric lymphoma?
Chronic antigen stimulation due to H.pylori
Treatment: H.pylori eradication - PPI, clarithromycin, amox/metro
What are the histological features of normal duodenal epithelium?
Glandular epithelium
Goblet cells
Villous architecture
Brunner’s glands (->alkali)
What are the pathological features of duodenal ulcers and their complications?
More common than gastric, seen in younger population
Epigastric pain, worse at night, relieved by food
RFs: H.pylori, NSAIDs, steroids, smoking, drugs
Complications: IDA, perforation
What are the pathological features of coeliac disease?
T cell mediated gluten intolerance -> villous atrophy + malabsorption
Steatorrhoea, abdo pain, bloating, n+v, weight loss, fatigue
FTT, IDA, dermatitis herpetiformis
How is coeliac disease diagnosed and treated?
Anti endomysial Ab, anti tissue transglutaminase Ab, anti gliadin Ab
Rx: lifelong gluten free diet
List causes of mechanical bowel obstruction
Constipation Diverticular disease Intussusception Adhesions Herniation Volvulus
List causes of acute and chronic colitis
Acute: infection, chemotherapy, radiotherapy, drugs?
Chronic: IBD, TB
List causes of ischaemia colitis
Vessel occlusion Small vessel disease Low flow states Obstruction commoner in 'watershed areas' Splenic flexure: SMA->IMA, Rectosigmoid: IMA->internal iliac
How is C.difficile treated?
- 14/7 oral metronidazole
- 14/7 oral metronidazole
- 10-14/7 oral vancomycin
Describe the pathophysiology of diverticular disease
High intraluminal pressure -> outpouchings at weak points in bowel wall
90% in L colon
Asymptomatic/PR bleeding
Complications: fever, peritonism, gross perforation, fistula, obstruction
Epidemiology of Crohn’s
F>M
20s
White
Mono zygotes twin concordance 50%
Pathophysiology of Crohns
Whole GIT involved: apthous mouth ulcers, skip lesions
Non caseating granulomas, transmural inflammation
Fistulae, fissures
Presentation: Intermittent pain, diarrhoea + fevers
Complications: Strictures, fistulae, abscesses, perforation
List the extra-GI manifestations of IBD
Uveitis + conjunctivitis
Erythema nodosum, pyoderma gangrenosum, erythema multiforme
Clubbing, sacroilitis, myositis, ankylosing spondylitis, pericholangitis
PSC - more common in UC
Diagnosis and management of Crohns
ESR + CRP ?barium contrast Endoscopy Rx: mild = prednisolone, severe = IV hydrocortisone, metronidazole + azathioprine, methotrexate, infliximab
Pathophysiology of ulcerative colitis
Continuous involvement of bowel mucosa extending proximally from rectum: Extensive superficial broad ulcers, no granulomas
Fissures, fistulae, strictures
Pseudo polyps: regenerating islands of mucosa
Small bowel only affected if there is backwash ileitis
Presentation: bloody diarrhoea, mucus, crampy abdo pain
Complications: severe haemorrhage, toxic megacolon
30% req colectomy in 3 yrs
20-30x risk adenocarcinoma
Diagnosis and management of UC
Rectal biopsy, AXR, stool culture Flexible sig / colonoscopy Mild: pred + mesalazine Mod: pred + 5ASA + BD steroid enema Sev: admit NBM, fluids + IV hydrocortisone, rectal steroids Remission: 5ASA (azathioprine 2nd line)
Describe carcinoid syndrome
Bronchoconstriction, flushing + diarrhoea due to:
Heterogenous gp of tumours of enterochromaffin cell origin
Produce serotonin -5HT
Oft found in bowel ( lung, ovaries, testes )
Slow growing
Describe carcinoid crisis
Life threatening vasodilation Hypotension Tachycardia Bronchoconstriction Hyperglycaemia
Describe the diagnosis and treatment of carcinoid syndrome
24 hr urine 5-HIAA (main metabolite of serotonin)
Rx: octreotide (somatostatin analogue)
Describe FAP: familial adenomatous polyposis
Familial syndrome ->untreated -> bowel adenocarcinoma 30yrs
70% AD 5q1 APC gene mut, 30% AR DNA mismatch repair gene mut
>100 adenomatous polyps by 10-15 yrs
Req prophylactic colectomy
Incr risk neoplasia: ampulla of vater + stomach
Hypertrophy of retinal pigment epithelium at birth
Describe Gardeners syndrome
Like FAP
+ extraintestinal features:
Osteomas, dental caries
Describe HNPCC: hereditary non-polyposis colorectal cancer
Aka lynch syndrome
AD mut in DNA mismatch repair
R colon: few polyps, fast progression
Describe adenomas
Benign dysplastic lesions precursor to most adenocarcinomas
Asymptomatic, req regular surveillance
>3.4cm: 45% malignant
Can be tubular, tubulo-villous + villous
Villous= rare but leak protein + K
RF for malig: large size, degree of dysplasia, villous component
Describe harmatomatous polyps
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