Histopathology Part 1- (p135-148- Cardio and Resp) Flashcards
(87 cards)
1
Q
Which WBCs are responsible for acute inflammation?
A
Neutrophils and macrophages (late acute)
2
Q
Which WBCs are responsible for chronic inflammation?
A
Macrophages (including granulomas like sarcoidosis), lymphocytes and plasma cells
3
Q
Which WBC is involved in allergic reactions and parasitic infections?
A
Eosinophils
4
Q
Two types of carcinoma?
A
Squamous cell carcinoma
Adenocarcinoma
5
Q
Histological features of squamous cell carcinoma?
A
Keratin production
Intracellular bridges
Don’t form glands
6
Q
Sites of squamous cell carcinomas?
A
Skin H+N Oesophagus Anus Cervix Vagina
7
Q
Histological features of adenocarcinoma?
A
Form glands -> secrete glandular fluid
Mucin production
8
Q
Sites of adenocarcinoma?
A
Lung Breast Stomach Colon Pancreas
9
Q
What is the Congo Red stain used to detect?
A
Amyloidosis- +ve apple green birefringence
10
Q
What does a positive result for the Prussian Blue stain show?
A
Iron (haemochromatosis)
11
Q
What is the definition of atherosclerosis?
A
Chronic inflammation in intima of large arteries characterised by intimal thickening and lipid accumulation
12
Q
What are the 7 steps of atherogenesis?
A
- Endothelial injury
- LDL enters intima and is trapped in subintimal space
- LDL converted into modified and oxidised LDL causing inflammation
- Macrophages take up oxLDL via scavenger receptors and become foam cells
- Apoptosis of foam cells causing inflammation and cholesterol core of plaque
- Increase in adhesion molecules on endothelium results in more macrophages and T cells entering the plaque
- VSMC form the fibrous cap
13
Q
3 principal components of atherosclerotic plaques?
A
Cells- including SMC, macrophages and other leukocytes
ECM including collagen
Intracellular and extracellular lipid
14
Q
Where is atherosclerosis more common?
A
Areas of turbulent blood flow where there is low shear stress which is atherogenic e.g. ostia of major branches
15
Q
Risk factors for atherosclerosis (modifiable and non-modifiable)?
A
Modifiable- T2DM, HTN, Hypercholesterolaemia and Smoking
Non-modifiable- Gender (M>F), age, FHx
16
Q
Complications of myocardial infarction?
A
Mechanical- Contractile dysfunction due to loss of muscle -> cardiogenic shock Congestive cardiac failure LV infarct Cardiac rupture Ventricular aneurysm
Arrhythmias-
VF usually occurs in first 24h, cause of sudden death
90% develop arrhythmia following MI
Pericardial- pericarditis, tamponade, Dressler’s syndrome (months after)
17
Q
What are the histological findings <6h post-MI?
A
Normal by histology (CK-MB also normal
18
Q
What are the histological findings 6-24h post-MI?
A
Loss of nuclei, homogenous cytoplasm, necrotic cell death
19
Q
What are the histological findings 1-4d post-MI?
A
Infiltration of polymorphs then macrophages (clear up debris)
20
Q
What are the histological findings 5-10d post-MI?
A
Removal of debris
21
Q
What are the histological findings 1-2w post-MI?
A
Granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
22
Q
What are the histological findings wks-months post-MI?
A
Strengthening, decellularlising scar tissue
23
Q
Common causes of HF?
A
IHD Valve disease Myocarditis HTN DCM Arrhythmias
24
Q
Complications of HF?
A
Sudden death Emboli Arrhythmias DVT + PE Pulmonary oedema Hepatic cirrhosis- nutmeg liver
25
Pathophysiology of HF?
Damage -> reduced CO + SV
Compensatory mechanisms:
Low CO -> Activation of RAS -> Salt and water retention to maintain perfusion. Eventually -> fluid overload
Low SV -> Activation of SNS via baroreceptors -> maintains perfusion but increases TPR -> increased afterload -> LVH and increased EDV -> dilatation and poor contractility
26
Investigations in HF?
BNP
CXR
ECG
Echo
27
Causes of dilated cardiomyopathy?
```
Idiopathic
Alcohol
Peripartum
Genetic
Sarcoidosis
Haemochromatosis
Myocarditis
```
28
Causes of HCM?
Genetic
| Storage diseases
29
Causes of restrictive cardiomyopathy?
Sarcoidoisis
Amyloidosis
Radiation-induced fibrosis
30
What is seen histologically in HCM?
Myocyte disarray
31
What is the inheritance pattern of HCM?
Autosomal dominant mutations in genes encoding sarcomeric proteins
32
Which mutations are most common for HCM?
betaMHC gene, MYBP-C + Trop-T
33
What is hypertrophic obstructive cardiomyopathy?
Septal hypertrophy resulting in outflow tract obstruction
34
What is arrhythmogenic right ventricular cardiomyopathy?
Myocyte loss with fibrofatty replacement typically affecting the RV
35
What is the peak age of acute rheumatic fever?
5-15yrs
36
What are the clinical features of Acute Rheumatic Fever and what is diagnosis based on?
Develops 2-4w after strep throat infection
Diagnosis is based on group A strep infection + 2 major criteria or 1 major and 2 minor criteria
```
Jones' Major Criteria (CASES)-
Carditis
Arthritis
Sydenham's chorea
Erythema marginatum
Subcutaneous nodules
```
```
Minor criteria:
Fever
Raised ESR or CRP
Migratory arthralgia
Prolonged PR interval
Previous rheumatic fever
Malaise
Tachycardia
```
37
Main pathogen in acute rheumatic fever?
Lancefield group A strep
38
Histology of acute rheumatic fever?
```
Beady fibrous vegetations (verrucae)
Aschoff bodies (small giant cell granulomas)
Anitschkov myocytes (regenerating myocytes)
```
39
Treatment of acute rheumatic fever?
Benzylpenicillin
40
What is the pathology of rheumatic heart disease?
Antigenic mimicry- cross reaction of anti-streptococcal antibodies with heart tissue
41
What increases the risk of bacteraemia?
```
Poor dental hygiene
IVDU
Soft tissue infection
Dental treatment
Cannulae/lines
Cardiac surgery
```
42
Causative organisms in acute infective endocarditis?
Staph aureus and strep pyogenes
43
Causative organisms in subacute infective endocarditis?
Strep viridans, staph epidermis, GACEK, coxiella, mycoplasma
44
Clinic features of infective endocarditis?
Constitutional- fever, malaise, rigors and anaemia
Cardiac- new murmur (MR/AR usually)
Immune phenomena- Roth spots, Osler's nodes + haematuria due to glomerulonephritis
Thromboembolic phenomena- Janeway lesions, septic abscesses in lungs/brain/spleen/kidney, microemboli, splinter haemorrhages, splenomegaly
45
Criteria used for diagnosing infective endocarditis?
Duke criteria:
Major-
Positive blood culture growing typical organisms or 2 positive cultures >12h apart
Evidence of vegetation/abscess on echo or new murmur
```
Minor-
RF
Fever>38
Thromboembolic phenomena
Immune phenomena
Positive blood cultures not meeting major criteria
```
Need 2 major, 1 major + 3 minor or 5 minor
46
How do you treat infective endocarditis?
Broad spectrum Abx once cultures taken, then treat according to sensitivies
Subacute- benzylpenicillin + gentamicin or vancomycin for 4wks
Acute- Flucloxacillin for MSSA, rifampicin + vancomycin + gentamicin for MRSA
47
Causes of pericarditis?
```
Fibrinous (MI, uraemia)
Purulent (staph)
Granulomatous (TB)
Hemorrhagic (tumour, TB, uraemia)
Fibrous (constrictive)
```
48
Common cause of pericardial effusion?
Chronic heart failure
49
Histological features of chronic bronchitis?
Dilatation of airways
Goblet cell hyperplasia
Hypertrophy of mucous glands
50
Histology of bronchiectasis?
Permanant dilatation of bronchi and scarring
51
Histology of asthma?
Whirls of shed epithelium (Curschmann spirals), eosinophils, Charcot-Leyden crystals
52
Histology of emphysema?
Loss of alveolar parenchyma distal to terminal bronchiole
53
Causes of bronchiectasis?
```
Inflammatory-
Post-infectious
Abnormal host defence (hypogammaglobulinaemia or chemotherapy)
Obstruction
Post-inflammatory
Secondary to bronchiolar disease or interstitial fibrosis
Systemic disease
Asthma
```
```
Congenital-
CF
PCD
Hypogammaglobulinaemia
Yellow nail syndrome
Young's syndrome- rhinosinusistis, azoospermia and bronchiectasis
```
54
What is interstitial lung disease?
Group of >200 diseases characterised by inflammation and fibrosis of the pulmonary connective tissue, particularly the most peripheral and delicate interstitium of the alveolar wall
55
What do you see on spirometry for interstitial lung disease?
Features of restrictive lung disease:
Decreased CO diffusion capacity
Decreased lung volume
Decreased compliance
56
How does interstitial lung disease present?
SOB
*End-inspiratory crackles*
Cyanosis, pulmonary HTN and cor pulmonale
Honeycomb lung
57
How is interstitial lung disease categorised?
1. Fibrosing e.g. cryptogenic fibrosing alveolitis, pneumoconiosis, CTD
2. Granulomatous e.g. sarcoid, EAA
3. Eosinophilic
4. Smoking-related
58
What is the histological pattern of fibrosis in cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?
Usual interstitial pneumonia (required for diagnosis):
Progressive patchy interstitial fibrosis with loss of normal lung architecture and honeycomb change, beginning at periphery of lobule, usually sub-pleural
Hyperplasia of type II pneumocytes causing cyst formation- honeycomb fibrosis
59
Clinical presentation of cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?
Increasing exertional dyspnoea and non-productive cough
| 40-70y at presentation with hypoxemia -> cyanosis and pulmonary HTN
60
Treatment for cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?
Steroids
Cyclophosphamide
Azathioprine
61
What is pneumoconiosis?
Typically occupational lung disease- a non-neoplastic lung reaction to the inhalation of mineral dusts or inorganic particles (majority affect upper lobe e.g. coal worker's pneumoconiosis, silicosis, asbestosis)
62
What is a granuloma?
A collection of histiocytes, macrophages +/- multi-nucleate giant cells
63
Name some granulomatous infections
TB
Fungal- histoplasma, cryptococcus, coccidioides, aspergillus, mucor
Pneumocystitis
Parasites
64
Name some non-infectious granulomatous conditions?
Sarcoid
Foreign body (aspiration or IVDU)
Drugs
Occupational lung disease
65
What is extrinsic allergic alveolitis?
Group of immune-mediated lung disorders caused by intense/prolonged exposure to inhaled organic antigens -> widespread ALVEOLAR inflammation. Typically an occupational lung disease
66
What do you see histologically in extrinsic allergic alveolitis?
Presence of polypoid plugs of loose connective tissue within alveoli/bronchioles- granuloma formation and organising pneumonia
67
How does acute EAA present?
Inhalation of antigenic dust in sensitised individual -> systemic symptoms (fever, chills, chest pain, SOB, cough) within hours of exposure, usually settle by following day. Progresses to chronic EAA
68
How does chronic EAA present?
Progressive persistent productive cough and SOB, finger clubbing and severe weight loss
69
Name some common chronic EAA conditions and what causes them?
```
Farmer's lung- mouldy hay/grain/silage
Pigeon fanciers lung- proteins in excreta/feathers
Humidifiers lung- heated water reserves
Malt workers lung- germinating barley
Cheese washer's lung- mouldy cheese
```
70
What are the four common forms of lung cancer and who do they commonly occur in?
Squamous cell carcinoma (30-50%)- M>F, smokers
Adenocarcinoma (20-30%)- women and non-smokers
Small cell carcinoma (20-25%)- smokers
Large cell carcinoma (10-15%)
71
What mutations most commonly cause squamous cell carcinoma?
p53/c-myc mutations
72
Where does squamous cell carcinoma most commonly occur?
Proximal bronchi, late mestastasis
73
Histology of squamous cell carcinoma?
```
Keratinisation
Intracellular prickles (Desmosomes)
```
74
What is adenocarcinoma?
Malignant epithelial tumour with glandular differentiation or mucin production
75
Where does adenocarcinoma most commonly occur?
Peripherally and metastasises early
76
Histology of adenocarcinoma?
Glandular differentiation (gland formation and mucin production)
77
Where does small cell carcinoma usually occur?
Centrally in proximal bronchi, early metastasis to bone, adrenal, liver and brain
78
What sort of cells does small cell carcinoma arise from?
Neuroendocrine- associated with ectopic ACTH, Lambert-Eaton, cerebellar degeneration
79
What is a large cell carcinoma?
Poorly differentiated malignant epithelial tumour- large cells, large nuclei, prominent nucleoli
80
Histology of large cell carcinoma?
No evidence of glandular or squamous differentiation
81
What percentage of PEs derive from DVTs?
95%
82
RF for PE?
```
Female
Immobility
Cardiac disease
Cancer
Primary and secondary hypercoaguable
```
83
Virchow's triad?
Blood stasis
Damage to endothelium
Hypercoagulability
84
What is the clinical definition of pulmonary HTN?
Mean pulmonary arterial pressure >25mmHg at rest
85
How is pulmonary HTN classified?
According to aetiology
Class 1- PAH (idiopathic, hereditary, drugs/toxins)
Class 2- Pulmonary HTN associated with left heart disease (systolic/diastolic dysfunction, valve disease)
Class 3- Pulmonary HTN due to lung disease
Class 4- Chronic thromboembolic pulmonary HTN
Class 5- Pulmonary HTN with unclear multifactorial mechanisms (metabolic disorders, systemic disorders, haematological disorders)
86
What is the pathophysiology of pulmonary oedema?
Intra-alveolar fluid accumulation leads to poor gas exchange
87
Main aetiology of pulmonary oedema?
LHF
