Histopathology Flashcards
Atherosclerosis
chronic inflammation in intima of large arteries, characterised by intimal thickening and lipid accumulation
7 steps of atherogensis
- endothelial injury 2. LDL enters intima and is trapped 3. LDL is coverted into oxidised LDL causing inflammation 4. Macrophages take up oxLDL -> foam cells 5. apoptosis of foam cells cause inflammation and cholesterol core of plaque 6. increase in adhesion molecules on endothelium attracts more macrophages and T cells enetering the plaque 7. Vascular smooth muscle cells form the fibrous cap
Artheroslerotic plaques - 3 components
- Cells (macrophages, smooth muscle cells, leukocytes) 2. ECM including collagen 3. intracellular and extracellular lipid
Where is most likely for atherosclerosis to occur?
Ostia (origins) of major branches. Turbulent flow and low shear stress.
Risk Factors for artherosclerosis a) modifiable (4) b) non-modifiable (3)
a) T2DM, HTN, hypercholesterolaemia, smoking b) M>F, FH, age
Angina
transient chest pain due to reversible myocardial ischaemeia
Stable Angina
chest pain on exertion
Unstable Angina
chest pain at rest
Prinzmetal/Variant Angina
rare younger patients due to coronary artery spasm
Ischaemia
an imbalance between perfusion and myocardial O2 demand
Myocardial Infarction
full occlusion pf coronary artery by thrombus overlying a disrupted plaque -> secondary necrosis of myocardium - 20-40mins results in irreversible injury and myocyte death
Complications of MI
a) Mechanical - ventricular dysfunction, cardiogenic shock, MR, papillary muscle rupture b)Arrhythmia’s - VF - 90% c) Pericardial - pericarditis, effusion d) systemic - embolisation -> PE
Dressler’s Syndrome
Weeks - months post-MI - Pleuritic chest pain - Fever - Pericardial effusion Check ESR
Heart failure Causes (6)
the inability of the heart to meet the demands of the tissue 1. IHD 2. Valvular disease 3. Myocariditis 4. HTN 5. dilated cardiomyopathy 6. arrhythmias
Nutmeg Liver
An effect of RHF Congestion of portal venous system -> peripheral oedema -> hepatomegaly
Pulmonary oedema (5) symptoms
An effect of LHF Congestion of pulmonary circulation - > pink transudate 1. dyspnoea 2. orthopnoea 3. PND “paroxnysnal nocturnal dyspnoea” 4. wheeze 5. fatigue
Signs of RHF (4)
- Peripheral oedema 2. ascites 3. facial engorgement 4. hepatomegaly
Hypertrophic Cardiac Myopathy a - pattern of inheritance b - most common mutation c - other mutations d - outcome
a - autosomal dominant b - BMHC - gene encoding sarcomeric proteins c - MYBP-C, Trop-T d - sudden cardiac death
Hypertrophic Obstructive Cardiomyopathy (HOCM)
assymmetric septal hypertrophy means blood is unable to pump past muscle
Arrythmogenic Right Ventricular Cardiomyopathy (ARVC)
- presents in early adulthood - myocyte loss with associated fibrofatty replacement
Acute Rheumatic Fever a - pathogen b - when c - histology (3) d - symptoms (4) e - effects on heart (3) - effect on joints (2) - effects on skin (2) - effects on neuro (2) f - treatment g - chronic problems
a - Lancefield group A Strep b - 2-4weeks post Strep throat c - beady fibrous vegetations “verrucae”, Aschoff bodies, Anitschkov myocytes d - fever, tachycardia, malaise, MIGRATING POLYMYALGIA e - “pancarditis” - endocaridits + myocarditis + pericarditis - arthritis + synovitis - erythema marginatum + subcutaneous nodules - encephalopathy + Sydenham’s chorea f - Benzylpenicillin or Erythromycin in pen-allergic g - Mitral valve pathology
Infective Endocarditis (IE)
colonisation or invasion of heart valves or mural endocardium by microbe
Causes of IE (6)
- poor dental hygiene 2. IVDU 3. soft tissue infection 4. dental treatments 5. cannulae/lines 6. cardiac surgery/pacemakers
Predisposing factors of IE (6)
- rheumatic heart disease 2. mitral valve prolapse 3. calcified valves 4. biscuspid aortic valves 5. prosthetic valves 6. congenital defects
Pathogens in acute IE (2) (previously healthy valve)
Staph aureus Strep pyogenes
Pathogens in subacute IE (6) (previous valve pathology)
step viridans staph epidermis HACEK Coxiella Mycoplasma Candida
Symptoms of IE (3) Signs of IE (7) Treatment (2)
Symptoms - fever - malaise - rigors Signs - anaemia - splenomegaly - new murmur - Roth spots - splinter hemorrhages - Janeway lesions - Osler’s nodes Treatment - Benzylpenicillin + Gentamicin
Pericarditis - 5 types
- inflammation of the percardium 1. Fibrinous - MI, uraemia 2. Purulent - Staph 3. Granulomatous - TB 4. Haemorrhagic - tumour, TB 5. Fibrous (constrictive)
Histological features of chronic bronchitis (2)
- goblet cell hyperplasia 2. hypertrophy of mucous glands
Histological feature of bronchiectasis
permanent dilatation of bronchi - mucus plugging
Histological features of asthma (3)
- Curschmann spirals (whorls of shed epithelium) 2. eosinophils 3. Charcot-Leyden crystals
Kartagener’s Syndrome - inheritance pattern - pathology - triad
- autosomal recessive - defective cilia motility Triad 1. situs inversus 2. bronchiectasis 3. chronic sinusitis
Sign of interstitial lung disease
End inspiratory crackles
Histology hallmark of interstitial lung disease
honey comb lung
Idiopathic Pulmonary Fibrosis -who -where -presentation (2) -complications (3) -treatment (2)
- M>F 40-70yo - lower lobes - dyspnoea, non-productive cough - clubbing, pulmonary HTN, cyanosis - steroids, azathioprine, cyclophosphamide
Conditions associated with lung fibrosis (4)
- Rheumatoid arthritis 2. Systemic sclerosis 3. SLE 4. connective tissue disease
Pneumoconiosis - who - where - what
- coal workers - upper lobes - non-neoplastic lung reaction to inhalation of mineral dust/inorganic particles
Causes of OBSTRUCTIVE lung disease (5)
- chronic bronchitis 2. bronchiectasis 3. asthma 4. emphysema 5. bronchiolitis
Causes of Bronchiectasis a) inflammatory (7) b) congenital (3)
a) inflammatory 1. post-infectious 2. abnormal host defense 3. ciliary dyskinesia 4. obstruction 5. post-aspiration 6. secondary to bronchiolar disease and interstitial fibrosis 7. connective tissue disorders 8. asthma b) congenital 1. CF 2. ciliary diskinesia 3. hypogammaglobulinema
Hypogammaglobinlinema - what - predisposition - treatment
= primary immune deficiency disease - recurrent infections, predisposed to Strep. pneumonniae, H.influenzae - IVIG
Features of RESTRICTIVE lung disease (3)
- reduced CO diffusion capacity 2. decreased lung volume 3. decreased compliance
What is interstitial lung disease?
group of > 200 disease characterised by inflammation and fibrosis of the pulmonary connective tissue, particularly the peripheral interstitium of the alveolar wall
What drug can induce fibrosing lung disease?
Amiodarone (anti-arrhythmic)
What area of the lung is affected in a) pneumoconiosis b) silicosis c) asbesotosis
a - upper lobe b - upper lobe c - lower lobe
Causes of granulomatous interstitial lung disease (3)
- Sarcoidosis 2. extrinsic allergic alveolitis 3. Vasculitides
Extrinsic Allergic Alveolitis (EAA) - cause - result - histology - who - management
- immune-mediated response to inhaled organic antigens - widespread alveolar inflammation - plugs of connective tissue within alveoli, granuloma formation, organising pneumonia - pigeon fancier’s, farmers, malt-workers, cheese washers - removal of antigen
Wegener’s Granulomatosis - what - features (4) - marker - treatment
- autoimmune vasculitis of small and medium blood vessels 1. conjunctivitis 2.pulmonary disease 3. sinusitis 4. myalgia - c-ANCA - Azathioprine/Methotrexate
Churg-Strauss Syndrome - 6 features
small - medium vessel vasculitis Features : - 1. Asthma (wheezing, expiratory rhonchi) 2. Eosinophilia of more than 10% in peripheral blood 3. Paranasal sinusitis 4. Pulmonary infiltrates (may be transient) 5. Histological proof of vasculitis with extravascular eosinophils 6. Mononeuritis multiplex or polyneuropathy
Squamous Cell Carcinoma of lung - risk factors (2) - common mutations (2) - histological features (2) - where - ectopic secretion - metastasis
- M>F, smoker - p53, c-myc - desmosomes (intercellular prickles), keratinisation - centrally located tumours - PTH-like peptide -> hypercalcaemia - late metastasis
Adenocarcinoma of lung - risk factors (2) -common mutation - histological features (3) - where - treatment
- F>M, non-smokers - EGFR mutations - glandular differentiation, gland formation, mucin production - peripherally - tyrosine kinase inhibitors
Small Cell Carcinoma of lung - risk factors - common mutations (2) - histological feature - where - ectopic secretion - associations (2) - metastasis
- smoking - p53, RB1 - arise from neuroendocrine cells - centrally - ACTH - Lambert-Eaton syndrome, cerebellar degeneration - rapid
Large Cell carcinoma of the lung - prognosis - microscopy - ectopic secretions (7)
- very poor - poor differentiation, large cells, large nuclei - ADH, ACTH, PTH, PTHrP, Calcitonin,Serotonin, Bradykinin
Mesothelioma - association - symptoms (3) - time period
- asbestos - 1. chest pain 2. dyspnoea 3. pleural effusion - latent period 25-45years
Risk factors for PE (8)
- female 2. COCP 3. Preganancy 4. post-surgery 5. immobility 6. cardiac disease 7. malignancy 8. hypercoagulable states
Complications of PE (2)
- corpulmonale -> RHF 2. cardiogenic shock
Causes of Pulmonary HTN a) primary b) secondary (4)
a) idiopathic b) 1. chronic lung disease 2.heart disease 3. recurrent thrombo-emboli 4. AI disorders
Pulmonary oedema - histology
iron laden macrophages
Hyaline Membrane Disease (HMD) - who - why - what cells - histology
- prem neonates - insufficient surfactant production - type II pneumocytes - lung expanded, plum coloured
What cells line to oesophagus?
proximal 2/3 - squamous epithelium distal 1/3 - columnar epithelium joined by the squamo-coloumnar junction “Z-line”
Treatment of GORD (3)
- Smoking cessation 2. Weight loss 3. PPI
Barrett’s Oesophagus - what - risk
- SCJ transition, metaplasia of squamous cells to columnar cells - increased risk of Ca
Oesophageal adenocarcinoma - risk factors (6) - where in the oesophagus?
- M>>F 2. Caucasian 3. Smoking 4. Barrett’s oesophagus 5. obesity 6. radiation therapy - distal 1/3
Plummer-Vinson Syndrome
iron deficiency anaemia + dysphagia
Squamous Cell Oesophageal Carcinoma - Risk Factors (7) - where in the oesophagus? - prognosis - presentation (4)
- alcohol 2. smoking 3. M>F 4. Afro-Caribbean 5. nutritional deficiencies 6. Plummer-Vinson syndrome 7. HPV - middle 1/3 - poor - rapid growth & metastasis - progressive dysphagia, odynophagia, anorexia, weight loss
What cells line the stomach?
columnar epithelium
Causes of acute gastritis (5) Complications of gastritis (2)
- aspirin 2. NSAIDs 3. H pylori 4. stress 5. corrosives 1. gastric ulcer formation 2. intestinal Ca
Cells involved in acute gastritis
neutrophils
Cells involved in chronic gastritis
lymphocytes and plasma cells
Symptoms of GASTRIC ulcer (4)
- epigastric pain 2. weight loss 3. pain worsens with food 4. pain relieved by antacids
Histology of gastric ulcer
- breach through muscularis mucosa into submucosa - punches out lesion with rolled margins
Treatment of H.pylori (3)
- PPI 2. Clarithromycin 3. Amoxicillin/Metronidazole
Symptoms of DUODENAL ulcer (3)
- epigastric pain 2. pain is worse at night 3. pain is relieved by food/milk
Which is more common duodenal or gastric ulcer?
duodenal
Biopsy findings in Coeliac Disease (3)
- villous atrophy 2. crypt hyperplasia 3. lymphocyte infiltrate
What rash is associated with Coeliac Disease?
dermatitis herpetiformis
What serological markers are associated with Coeliac Disease? (3)
- Anti-endomysial Ab 2. Anti-tissue transglutaminase 3. Anti-gliadin
Symptoms of Coeliac Disease (8)
- steatorrhoea 2. abdo pain 3. bloating 4. N&V 5. weight loss 6. fatigue 7. IDA 8. failure to thrive
Coeliac Disease
T cell mediated autoimmune disease causing gluten intolerance
What GI disease is Down’s syndrome associated with?
Hirschsprung’s
Hirschsprung’s Disease - what - who - biopsy findings - genetic association - treatment
- absence of ganglion cells in myenteric plexus - M>>F - hypertrophied nerve fibres, no ganglia - RET proto-oncogene Cr10+ - resection of affected gut
Which is associated with BLOODY diarrhoea - crohn’s or UC?
Crohn’s
“Skip lesions” “cobblestone appearance” “rosethorn ulcers” are associated with which IBD?
Crohn’s
Complication of UC where the small bowel is involved?
backwash ileitis
Severe complication of UC?
toxic megacolon
Skin manifestations of IBD (3)
- erythema nodosum 2. pyoderma gangrenosum 3. erythema multiforme
Symptoms of Carcinoid Syndrome (7)
- flushing 2. diarrhoea 3. bronchoconstriction 4. vasodilation 5. HYPOtension 6. tahcycardia 7. HYPERglycaemia
Carcinoid syndrome is associated with which cells?
enterochromaffin cells
What do you look for if Carcinoid syndrome is suspected?
24hr urine - 5-HIAA (metabolite of serotonin)
gene associated with colorectal adenoma?
APC (adenomatous polyposis coli)
Juvenile Polyposis - inheritance pattern - symptoms - risk
- autosomal dominant - PR bleeding from harmatomatous polyps - haemorrhage
Peutz-Jeghers Syndrome - pattern of inheritance - mutation - signs (4) - presentation
- autosomal dominant - LKB1 - 1. freckling of lips and around the mouth 2. mucocutaneous hyperpigmentation 3. freckling of palms and soles of feets 4. multiple polyps - intussuseption
Risk factors associated with colorectal Ca (6)
- low fibre diet 2. high fat diet 3. lack of exercise 4. obesity 5. chronic IBD 6. familial syndromes
Staging of Colorectal Ca?
DUKE’S A - confined to mucosa B1 - extending into muscularis propria B2 - transmural invasion C1 - extending into muscularis propria + LN mets C2 - transmural invasion + LN mets D - distant mets
Genes associated with FAP a - autosomal dominant b - autosomal recessive
a - APC b - DNA mismatch repair genes
Gardner’s Syndrome - what? - features (3)
- similar to FAP but with ecxtra-intestinal features - osteomas, soft tissue tumours, dental caries
Lynch syndrome - otherwise known as? - inheritance pattern - mutation - associations (3)
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC) - autosomal dominant - DNA mismatch repair genes 1. endometrial 2. ovarian 3. stomach
where is secretin produced? what is it’s role?
- S-cells of the duodenum - to cause the pancreas to produce bicarbonate as a buffer
where is CCK produced? what is it’s role?
- I-cells of the duodenum - causes release of digestive enzymes from the pancreas
what do the alpha cells of the islets of Langerhans do?
secrete GLUCAGON to increase blood glucose
what do the beta cells of the islets of Langerhans do?
secrete INSULIN to decrease blood glucose
what do the delta cells of the islets of Langerhans do?
secrete SOMATOSTATIN to regulate alpha/beta cells
what do the D1 cells of the islets of Langerhans do?
secrete H20, a vasoactive peptide
Fasting plasma glucose level diagnostic of DM?
>7 mmol/L
Random plasma glucose level diagnostic of DM?
> 11.1 mmol/L
Signs of DM (3)
- polyuria 2. polydipsia (raised plasma osmolality 3. recurrent infections (hypergylacaemia)
Pathology of T1DM
Autoimmune destruction of BETA cells by CD4+ and CD8+ T-lymphocytes
Pathology of T2DM
linked to obesity of insulin resistance
Complications of DM a) Microvascular (3) b) Macrovascular (3)
a) 1. diabetic retinopathy 2. Neuropathy - poor healing ulcers 3. Peripherla Vascular Disease - claudication b) 1. Nephropathy - glomerulonephritis, pyelonephritis 2. Cardiac - MI 3. cerebral - CVA
What is a pseudocyst? - and what is it a complication of?
= a pathological collection of fluid - associated with alcoholic pancreatitis
Symptoms of acute pancreatitis (4)
- severe epigastric pain 2. pain that radiates to to the back 3. pain is relieved on sitting forward 4. vomiting
Histology of pancreatitis
coagulative necrosis
Causes of CHRONIC pancreatitis (5)
- alcoholism 2. CF 3. Hereditary 4. Pancreatic duct obstruction 5. Autoimmune (IgG4)
Presentation of CHRONIC pancreatitis (3)
- epigatsric pain radiating to the back 2. malabsorption 3. secondary DM
Histology of CHRONIC pancreatitis (4)
- fibrosis 2. loss of exocrine tissue 3. duct dilatation 4. calcification
Histology of Acinar Cell Carcinoma (2)
- neoplastic epithelial cells with eosinophilic granular cytoplasm 2. immunoreactivity for lipase, trypsin, chymotrypsin
Most common pancreatic cancer?
ductal adenocarcinoma (85%)
Risk factors of ductal adenocarcinoma (5)
- M>F 2. Age > 60yrs 3. smoking 4. diet 5. genetic (FAP, HNPCC)