Histo Flashcards
Atherosclerosis defined as
atheromatous deposits in and fibrosis of the inner layer of the arteries.
intimal lesions - atheroma (atheromatous plaques) - that protrude into vessel lumen
Stages of atherosclerosis
- Smooth endothelium damage.
- Platelets adhere to damaged tissue
- Proliferastion of endothelium
- Fibrous cap forms
- Deposition of cholesterol and enlargement of plaque with fatty core.
Atheromatous plaque definition
Raised legion, soft lipid core, white fibrous cap.
Pathogenesis of atherosclerosis
Endothelial injury
LDL accumulation
Monocyte adhesion and migration to intima forming macrophages and foam cells.
Platelet adhesion.
Fatty streak
Earliest lesion. lipid filled foamy macrophages, no flow disturbance, in all children >10y
Relationship to plaque unknow but in same sites.
Atherosclerotic Plaque
Patchy, localised flow disturbance, only involve a portion of the wall (rarely circumferential)
Composed of cells, lipid and matrix.
Critical stenosis occurs at
70% occlusion or diameter
Acute plaque changes (3)
Rupture - exposes prothrombotic plaque contents.
Erosion - exposes prothrombotic basement membrane
Haemorrhage into plaque increases size.
Reasons for a vulnerable plaque
Lots of foam cells of lipid
Thin cap
Few smooth muscle cells
Clusters inflammatory cells
Vasoconstriction effect on plaque
Reduces lumen size and increases mechanical pressure on plaque.
Due to adrenergic agonists
IHD main cause
90% due to reduced blood from from atherosclerosis.
IHD is leading cause of mortality for men and women. Due to lack of o2 to cardiac muscle less well tolerated that true hypoxia due to impaired waste clearance as well.
% stenosis of coronary arteries required to cause angina on exercise?
% stenosis to cause angina at rest?
75%
90% stenosis for pain at rest
MI pathogenesis
Loss of contractility in?
Irreversible after?
Myocardial blood supply compromised.
Loss of contractililty in 60s (so failure can precede myocyte death)
Irreversible after 20-30mins
Locations for MI
LAD 50%
RCA 40%
LCx 20%
% of asymptomatic MI
10-15% usually in elderly or DM.
Reperfusion injury cause
due to oxidative stress, Ca overload and inflammation. Arrhythmias are common
Complications of MI (6)
Mortality of MI is 30% in one year
Contractile dysfunction Arrhythmia Myocardial rupture Pericarditis RV infarction Deslers syndrome (pericarditis 2-3w post MI) Papillary muscle rupture
Chronic IHD definition
Progressive heart failure due to ischaemic myocaridal damage. May not be a prior infarction. Hypertrophies heart with dilated LV
Sudden Cardiac Death
Unexpected death in individuals without symptomatic heart disease or
Causes of sudden cardiac death
Acute MI is usually the trigger Marked atherosclerosis (>90%)
10% non atherosclerotic (long QT, HOCM)
Types of cardiomyopathy (3)
Dilated - progressive loss of myocytes
Hypertrophic
Restrictive
Causes of dilated cardiomyopathy
Idiopathic Infective Toxic - alcohol, chemo Hormonal - hyper/hypothyroid, DM, peripartum Genetic - haemochromatosis
Causes of hypertrophic cardiomyopath
Familial 50%
Causes of Restrictive Cardiomyopathy
Idiopathic or secondary to myocardial disease like amyloid or scarcoidosis.
Causes of Aortic Regurgitation
Rheumatic, degenerative rigidity Endocarditis Marfans Dissecting aneurysm Syphilitc aortitis Ankylosing spondylitis
Congenital Lung Pathology (3)
Lung agenesis or hypoplasia
Tracheical or bronchial stenosis
Congenital cysts
Causes of pulmonary oedema (4)
Left heart failure
Alveolar injury
Neurogenic
High altitude
Diffuse alveolar damage is caused by:
In adults acute respiratory distress syndrome (from infection, aspiration, trauma, DIC…)
In neonates by hyaline membrane disease.
Definition of chronic bronchitis
Chronic cough production of sputum for most days for at least 3m over at least 2 consecutive years
Complications of COPD
Repeated infections
Chronic hypoxia which results in pulmonary HTN and R heart failure.
Increased risk of lung Ca (independent of smoking)
Definition of emphysema
Permanent loss of alveolar parenchyma distal to terminal bronchiole. Usually due to smoking or aplha1 antitrypsin. Rarely IVDU or CTD
Parthenogenesis of emphysema
Chronic inflammation from cigarette etc cause neutrophil and macrophage activation. This least to the activation of proteases and tissue damage.
Complication of emphysema?
Bullae and pneumothorax
Respiratory failure
Pulmonary HTN and cor pulmonale.
Causes of Bronchiectasis
Post infections (esp in CF) Cillary dyskineasia (Kartageners) Obstruction Post-inflammatory (aspiration) Asthma Congential
Bronchopneumonia
Usually in elderly from low virulence organisms.
Patchy bronchial and peribronchial distribution, often lower lobes. Acute inflammation surrounding airways and in alveoli
Complications of infection of lung (5)
Abscess Pleuritis and pleural effusion Empyema Fibrous scarring Septicaemia
Causes of granulomatous lung infections
TB
Fungal (aspergillus, cryptococcus)
Pneumocystis
Parasites
Non-infectious granulomatous conditions?
Sarcoid
Foreign body aspiration or IVDU
Occupational lung disease
Sarcoidosis defintion
Idiopathic granulomatous disease of lung, skin, LNs and eyes. Due to abnormal immune response to common antigens.
Pathological changes in Lung sarcoid
Discrete epithelioid and giant cell granulomas usually in upper lobes. Usually perilymph or peribronchial. Elevated ACE
Causes of pulmonary hypertension (pressure >25mmHg)
Chronic hypoxia, congenital heart defects, chronic liver disease, parasites (schistosomal), emboli, pulmonary fibrosis, left sided heart disease
Complications of pulmonary HTN
Right heart failure Venous congestion of organs (nutmeg liver) Peripheral oedema Pleural effusion or ascites Hypoxia
Pneumoconiosis
Permanent alteration of lung structure due to inhaled inorganic dust and tissue reaction (excluding bronchitis and emphysema).
Often upper lobe, usually fibrosis.
Silicosis, asbestosis, berylliosis, coal workers lung.
Commonest type of lung Ca
Are epithelial tumours Non-Small Cell Squamous 35% Adenocarcinoma 27% Large cell carcinoma 10%
Small Cell 20%
Lung cancer types most strongly associated with smoking
Small cell and squamous
Angiosquamous dysplasia
Seen in high risk smokers and Squamous cell ca.
Basement membrane thickening and vascular budding.
Squamous Cell Ca of Lung
35% of pulmonary Cas
Closely assoicated with smoking
Traditionall arisised from bronchial but can be peripheral.
Locally spreads and metastasises late.
Histologically - keratinisation, intercellular prickles
Adenocarcinoma of lung
27% of pulmonary ca smoking is a risk Usually peripheral and multicentric Metastasises early Histology shows evidence of glandular differentiation.
Large cell ca of lung
10% of lung Ca
Peripheral or central tumours
Poorly differentiated, no histological evidence of glandular or squamous differentiation.
Poor prognosis.
Small Cell Ca
20% lung Ca Closely associated with Smoking Often central 80% present with advanced disease, is chemo sensitive but poor prognosis (survival 2-4m untreated, 10-20m treated). p53 and RB1 mutations are common Assoicated with paraneoplastic syndrome.
A predictive marker in Non-small cell lung Ca
ERCC1 (associated with poorer response to cisplatin)
Target for Non-small cell Lung Ca
EGFR with a tyrosine kinase inhibitor. If young, female, non-smoker. Contraindicated in Kras mutation.
Mutation in Lung Ca associated with poor prognosis
Kras
Paraneoplastic syndromes associated with Small Cell Lung Ca
SIADH
Cushing’s syndrome
Paraneoplastic syndrom associated with squamous cell lung Ca
Hypercalcaemia
Mesothelioma.
Frequency, aetiology, prognosis
A 20-year-old student gives an 8 hour history of very frequent vomiting and epigastric cramping. O/E she is pale and shivering. Her serum WBC is normal.
Gastroenteritis (Staphylococcus aureus)
Staphylococcus aureus is a leading cause of gastroenteritis resulting from the consumption of contaminated food.
Staphylococcal food poisoning is due to the absorption of staphylococcal enterotoxins preformed in the food.
The onset of symptoms is rapid (from 30 min to 8 h) and usually spontaneous remission is observed after 24 h.
As the presentation is so acute, the WCC often have not had a chance to increase (lag-time).
The symptoms of staphylococcal food poisoning are abdominal cramps, nausea, vomiting, sometimes followed by diarrhea
(never diarrhea alone).
How does HPV transform cells?
It posses two proteins E6 and E7 which bind and inactivate p53 and Rb (tumour suppressors).
A 63 year old obese, diabetic male presents to A and E with tight chest pain at rest, which radiated to the left arm and lasted for less than 20 minutes. The CK was not raised.
ACS
Acute coronary syndrome (unstable angina) is defined as recurrent episodes of angina on minimal effort or at rest and persists for longer than stable angina.
A 65 year old man is in hospital after suffering an acute myocardial infarction. The house officer hears a pansystolic murmur on auscultation.
Myomalacia cordis
Softening of the dead muscle leading rupture.
A 46 year old women presents to AandE out of breath and with severe chest pain. On examination a mid systolic click late systolic murmur is revealed.
Myxomatous mitral valve.
Myxomatous degeneration is pathological weakening of soft tissue. Can lead to prolapse of mitral valve.
A 40 year old man presents with a sharp chest pain. He has a pericardial friction rub, diminished heart sounds and a raised JVP.
Pericarditis