Histopathology Flashcards
(113 cards)
1
Q
What locations are most at risk of atherosclerotic plaque formation?
A
Locations with turbulent flow: Coronary arteries AA Carotid arteries Iliac arteries
2
Q
What are the components of an atherosclerotic plaque?
A
Cellular: SMC, macrophages
Extra cellular membrane
Lipids
3
Q
What are non-modifiable risk factors for atherosclerosis?
A
Age: 5x incr risk >60 yrs
Male
FHx
Genetic risk ?
4
Q
What are modifiable risk factors for atherosclerosis?
A
HTN: incr risk by 60%
T2DM
Smoking
Hyperlipidaemia
5
Q
What is the process of atherosclerosis ?
A
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
6
Q
What are the risk factors for mortality with MI?
A
Incr age
Female
DM
Previous MI
7
Q
What are the histological changes which occur following an MI?
A
Secs: reversible loss of contractility
20-30 mins: irreversible loss of contractility
8
Q
What occurs when the myocardium is starved of oxygen and nutrients in infarction?
A
60s: potentially reversible loss of contractility - acute HF
20-30 mins: irreversible loss of contractility
9
Q
What are immediate complications of MI?
A
40%
Cardiogenic shock: due to contractile dysfunction = mortality 70%
10
Q
What are acute complications of MI?
A
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
11
Q
What are chronic complications of MI?
A
> 1 wk: mural thrombus, ventricular aneurysm, PE
Wks- months: Dresslers pericarditis
Months-yrs: chronic HF
12
Q
What are the symptoms of Left HF?
A
Dyspnoea
Orthopnoea
PND
13
Q
What are the symptoms of Right HF?
A
Peripheral oedema
Ascites
Facial engorgement
14
Q
What are the causes of heart failure?
A
Ischaemic heart disease Valve disease HTN Myocarditis Cardiomyopathy Arrhythmias
15
Q
What are the complications of heart failure?
A
Sudden death Arrhythmias Systemic emboli Pulmonary oedema Hepatic cirrhosis
16
Q
What are the structural features of cardiac failure?
A
Dilated heart: scarring and thinning of walls
Microscopy shows scarring and replacement of myocardium
17
Q
What is the process by which heart failure develops?
A
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
18
Q
What are causes of aneurysm formation?
A
Congenital incl: Marcans
Atherosclerosis
HTN
19
Q
What is angina pectoris?
A
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
20
Q
What is prinzmetal angina?
A
Uncommon
Chest pain at rest
Due to coronary artery vasospasm
Unknown aetiology
21
Q
What are the features of sudden cardiac death?
A
Background of IHD + lethal arrhythmia
50% plaque rupture, 25% MI changes
Electrical instability at sites distant from conduction system, near scars from old ?MI
22
Q
What makes plaques vulnerable in atherosclerosis?
A
Lots of foam cells Thin fibrous cap Few SM cells Clusters of inflammatory cells HTN
23
Q
What are the features of hypertrophic cardiomyopathy?
A
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
24
Q
Dilated cardiomyopathy
A
Causes: idiopathic, alcohol, peripartum, genetic, sarcoidosis, haemochromatosis, myocarditis
Systolic dysfunction
Indirect dysfunction:
IHD, valvular heart disease, htn
25
Restrictive cardiomyopathy
Causes:
Sarcoidosis, amyloidosis, radiation induced fibrosis
Diastolic dysfunction
Indirect dysfunction: pericardial constriction
26
Hypertrophic cardiomyopathy
Causes: genetic, storage diseases
Diastolic dysfunction
Indirect dysfunction: HTN, AS
27
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
28
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
29
How is rheumatic fever diagnosed and treated?
Jones criteria
Plus raised ESR and ASOT
Benzylpenicillin
Or erythromycin if allergic
30
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
31
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
32
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
33
What type of endocarditis gives rise to small, warty, platelet rich, sterile vegetations?
Libman-Sachs
| Assoc with SLE + antiphospholipid synd
34
What might cause a bacteraemia leading to infective endocarditis?
Poor dental hygiene: strep viridans
IVDU: staph aureas
Iatrogenic: central lines, surgery
35
What factors predispose to endocarditis?
Rheumatic heart disease
Valve disease: e.g. Mitral prolapse, calcified valves
Prosthetic valves
Congenital defects: bicuspid aortic valve
36
What organisms might cause acute endocarditis?
Staph aureas
Strep pyogenes
High virulence with large vegetations, spread to aorta
37
What organisms might cause subacute endocarditis?
```
Strep viridans
Staph epidermis
HACEK
Coxiella
Mycoplasma
Candida
Low virulence with small vegetations, spreads to chordae
```
38
What are the clinical features of endocarditis?
Fever, malaise, anaemia, rigors
Splenomeg, new murmur
Roth spots, splinter haemorrhages, janeway lesions, oslers nodes
39
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
40
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
```
41
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
42
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
43
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
44
What is the pathophysiology underlying acute asthma?
Allergen sensitisation
T cell activation
IgE release from plasma cells
.????
45
What is the Pathophysiology underlying chronic asthma?
SMC hyperplasia
Increased mucus production
WBC infiltrates
46
What histological features are seen in asthma?
Eosinophils
Curschmann spirals: shed epithelium
Charcot-Leyden crystals
47
What histological features are seen in chronic bronchitis?
Airway damage:
Airway dilation
Goblet cell hyperplasia
Mucous gland hypertrophy
48
What are the complications seen with chronic bronchitis?
Recurrent infection
Chronic hypoxia
Pulmonary htn
49
What are the histological features of centrilobular emphysema?
Parenchyma damage:
Air space enlargement
Wall destruction
Loss of alveolar parenchyma distal to terminal bronchiole
50
What complications are associated with centrilobular emphysema?
Pneumothorax - due to bullae
Respiratory failure
Pulmonary htn
51
What is the cause of pan acinar emphysema?
Alpha-1-antitrypsin deficiency
52
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
53
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
```
54
What are congenital causes of bronchiectasis?
CF
Hypogammaglobulinaemia
Primary ciliary dyskinesia
55
What are the four categories of interstitial lung disease?
Fibrosing
Granulomatous
Eosinophilic
Smoking related
56
How might interstitial lung disease present?
SOB, end inspiratory crackles, cyanosis, pulmonary hypertension, cor pulmonale
Restrictive spirometry results
CXR: honeycomb features
57
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
```
58
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
59
What are the features of pneumoconiosis?
Occupational lung disease
Non neoplastic reaction to inhaled inorganic particles
Affecting upper lobe
E.g. Silicosis, asbestosis
60
What are the histological features of a granuloma?
Collection of histiocytes, macrophages
| With or without multinucelated giant cells
61
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
62
Features of bronchopneumonia
Low virulence organisms
Elderly/COPD
Patchy peribronchial distribution (often lower lobes)
63
Features of lobar pneumonia?
```
High virulence organisms
Young individuals
Fibrinosuppurative consolidation:
Red hepatisation: neutrophilia
Grey hepatisation: fibrosis
Resolution:
```
64
What is pulmonary hypertension?
Pulmonary pressure > 25 mmHg
65
What are causes of pulmonary hypertension?
Precapillary: vasoconstrictive or emboli
Capillary: pulmonary fibrosis
Post capillary: veno-occlusive disease or left HF
66
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
67
What are the histological features of pulmonary oedema?
Intra alveolar fluid
Iron laden macrophages
Diffuse alveolar damage
68
Causes of acute respiratory distress syndrome in adults?
Infection
Trauma incl burns
Aspiration
69
What are the histological features of rapid onset respiratory failure?
Expanded lungs:
firm
airless
plum coloured
70
Which lung cancers are most associated with smoking?
Small cell
| Squamous cell
71
Which lung cancer is commonest in non smokers?
Adenocarcinoma
72
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
73
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
74
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
75
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
76
Molecular markers in lung cancer:
| ERCC1
Poor response to cisplatin
77
Molecular markers in lung cancer:
| EGFR
Usually seen in adenocarcinoma
| Good response to TKI
78
Molecular markers in lung cancer:
| Kras
Seen in adeno/squamous carcinoma
No response to TKI
Poor prognosis
79
Molecular markers in lung cancer:
| EML4-ALK
Usually adenocarcinoma
| No benefit from TKI
80
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)
81
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
82
What are complications of reflux oesophagitis?
```
Ulceration
Haemorrhage
Barret's oesophagus
Stricture
Perforation
```
83
What is Barret's oesophagus?
Intestinal metaplasia of squamous mucosa = columnar epithelium with goblet cells
84
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
85
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
86
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
87
What are the pathological features of acute gastritis?
Neutrophil infiltrate
Following insult
E.g. Aspirin, NSAIDs, alcohol, corrosives, acute H.pylori
88
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
89
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
90
What are the pathological features of gastric lymphoma?
Chronic antigen stimulation due to H.pylori
| Treatment: H.pylori eradication - PPI, clarithromycin, amox/metro
91
What are the histological features of normal duodenal epithelium?
Glandular epithelium
Goblet cells
Villous architecture
Brunner's glands (->alkali)
92
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
93
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
94
How is coeliac disease diagnosed and treated?
Anti endomysial Ab, anti tissue transglutaminase Ab, anti gliadin Ab
Rx: lifelong gluten free diet
95
List causes of mechanical bowel obstruction
```
Constipation
Diverticular disease
Intussusception
Adhesions
Herniation
Volvulus
```
96
List causes of acute and chronic colitis
Acute: infection, chemotherapy, radiotherapy, drugs?
Chronic: IBD, TB
97
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
```
98
How is C.difficile treated?
1. 14/7 oral metronidazole
2. 14/7 oral metronidazole
3. 10-14/7 oral vancomycin
99
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
100
Epidemiology of Crohn's
F>M
20s
White
Mono zygotes twin concordance 50%
101
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
102
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
103
Diagnosis and management of Crohns
```
ESR + CRP
?barium contrast
Endoscopy
Rx: mild = prednisolone,
severe = IV hydrocortisone, metronidazole + azathioprine, methotrexate, infliximab
```
104
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
105
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)
```
106
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
107
Describe carcinoid crisis
```
Life threatening vasodilation
Hypotension
Tachycardia
Bronchoconstriction
Hyperglycaemia
```
108
Describe the diagnosis and treatment of carcinoid syndrome
24 hr urine 5-HIAA (main metabolite of serotonin)
| Rx: octreotide (somatostatin analogue)
109
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
110
Describe Gardeners syndrome
Like FAP
+ extraintestinal features:
Osteomas, dental caries
111
Describe HNPCC: hereditary non-polyposis colorectal cancer
| Aka lynch syndrome
AD mut in DNA mismatch repair
| R colon: few polyps, fast progression
112
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
113
Describe harmatomatous polyps
I
