Histopathology Notes
Cardiovascular Disease
BP = CO x SVR
CO = HR x SV
Infarction
· Necrosis due to ischaemia
· Arterial
o MI
o Stroke
o Bowel infarction
o Acute limb ischaemia
· Venous
o PE
o Torsion of vascular pedicle
o Sigmoid volvulus
o Testicular torsion
Atherosclerosis
· Arterial wall thickening and loss of elasticity
Stages
· Endothelial cell injury
· Inflammatory response in vessel wall
o Oxidised LDL
· Formation of stable atherosclerotic plaque
o Vascular smooth muscle phenotype shift
· Complication of stenosis or plaque rupture
Risk Factors
· Non-Modifiable
o Age
o Sex
o Family history
o Others - Type A personality, oestrogen deficiency
· Modifiable
o Hypertension
o Diabetes Mellitus
o Smoking
o Hypercholesterolaemia
o Others - physical inactivity, lipoprotein Lp(a)
Complications
· Plaque-related Stenosis (angina, intermittent claudication)
· Plaque rupture
o Thrombosis (MI, stroke, acute limb ischaemia)
o Embolism (MI, stroke, acute limb ichaemia)
· Weakening of vessel wall (AAA)
Acute Coronary Syndrome
· Unstable angina
o No cardiac damage (normal tropnin)
· NSTEMI/STEMI
o Cardiac damage (raised tropnin)
Acute Limb Ischaemia
· Thrombosis (60%)
o Hx of claudication/rest pain
o Onset over hours
o Signs of chronic vascularinsufficiency
o Hard arteries
o No bruits
· Embolism (30%)
o Recent MI, atrial fibrillation, aneurysm
o Onset over seconds
o No evidence of previous disease
o Soft artery
o Bruits
Hypertension
· 140/90 (based upon additional risk factors)
· 160/100 (absolute)
· Primary (essential) - 95%
o Idiopathic
· Secondary
o Renal disease
o Endocrine disease
o Pregnancy
o Drugs
Sequalae
· HTN retinopathy
· CVA
· ↑ Glucose levels
· HTN encephalopathy
· MI
· HTN Cardiomyopathy
· HTN Nephropathy
Cardiac Failure
A syndrome caused by any abnormality of the heart that may be characterised by a set of haemodynamic,
neural, and endocrine abnormalities
LVF
· Causes:
o IHD
o Hypertension
o Valve disease
o Myocardial disease
· Consequences:
o Impaired pulmonary outflow
§ Congestion and oedema
o Reduced renal perfusion
§ Salt and water retention + ATN
o Reduced CNS perfusion (encephalopathy)
RVF
· Causes:
o Left-sided heart failure (Congestive)
o Chronic Lung Pathology - Cor Pulmonale
· Consequences:
o Portal, systemic and peripheral congestion
o Tricuspid regurgitation
o Renal congestion (R > L)
Cardiomyopathy
Causes / FeaturesHypertrophic / Inherited (50% AD)
Sporadic cases / Pathology - heavy muscular hypertrophy with poor compliance
Often asymmetrical septal hypertrophy
Sequelae:
- Arrhythmias - AF
- LV outflow obstruction
- CHF
- Sudden deathYoung man
Syncope, FH of sudden death, Jerky pulse and double apical impulse, Ejection systolic murmur (+/- mild mitral murmur)
Dilated / Idiopathic
Genetic
Infections e.g. viral myocarditis
Toxins - alcohol, chemotherapy / Four-chambered hypertrophy and dilatation
Poor prognosis
Progressive CCF
Progressive loss of mycoytes causing dilation + heart failure + arrhythmias
Restrictive / Pathology - restriction of ventricular filling with myocardial fibrosis
ARVD / Inflammation and thinning of the right ventricular wall
Usually due to mutation in cell adhesion genes / Key consequences:
- Arrhythmia
- CCF
Valve Disease
Congenital
· Abnormalities e.g. Bicuspid valves
Acquired
· Rheumatic fever/Endocarditis
· Functional (e.g. Mitral/tricuspid valve disease)
· Degeneration (e.g calcific aortic stenosis)
Stenosis
· Pressure overload + hypertrophy
· Develops slowly
Regurgitation
· Volume overload
· Develops quickly or slowly
Complications
· Hypertrophy
o LVF
o Worsening of IHD, heart failure
o Pro-arrhthymia
· Dilation
o Mitral and atria
· Risk of Endocarditis
Types / Pathogenesis / FeaturesRheumatic Fever / Acute inflammatory disorder of children (5-15)
Post-streptococcal (5 weeks) / Foci of fibrinoid necrosis → Aschoff Bodies, Fibrinous pericarditis, Valvulitis
Fribrous thickening + commissural fusion, MacCallum plaques
Infective Endocarditis / Acute / Usually stap. aureus
Very virilant, IV drug users, Very severe / Bulky vegitations with lots of erosion
May produce an abscess
Subacute / Usually strep. viridans
Less virulent, Prosthetic valves, Long course / Small vegetations with little erosion
Pathology of the Lung
Respiratory Failure
· End-stage of all pulmonary disease
· PaO2 < 8 kpa
Type I respiratory failure
· Severe pneumonia, PE, asthma, fibrosis, LVF
· V/Q Imbalance
o CO2 - Compensation (pCO2 - normal/low)
o O2 – No compensation
Type II respiratory failure
· COPD, neuromuscular disease, severe acute asthma
· Hypoventilation
o Impaired transfer of Co2 and O2 (pCO2 elevated)
Pulmonary Embolus
· 95% of PE from deep vein thrombi in legs/pelvis
· Large - Instant death (acute cor pulmonale)
· Medium - Chest pain + pulmonary heamorrhage
· Small - Clinically silent (multiple → Pulm. HTN)
· Ix: ECG + D-Dimer
Primary Pulmonary Hypertension
· Unknown cause
· > 25mmHg pressure at rest
· Young women
· Complication → Right ventricular failure
· Tx: vasodilators/lung transplantation
RVF
· Causes:
o Left-sided heart failure (congestive)
o Chronic lung pathology → cor Pulmonale
· Consequences:
o Portal, systemic and peripheral congestion
o Tricuspid regurgitation
o Renal congestion (R > L)
Obstructive pulmonary disease
These are characterized by an increased resistance to airflow (low FEV1 and FEV1/FVC < 0.7)
Asthma
· Kids > adults
· Chronic airways inflammation that is usually reversible
· Part of an atopic trait
· Can be severe and life-threatening
· Macroscopic
o Overinflated, patchy atelectasis, mucus plugs
· Microscopic
o Oedema, pulmonary infiltrates (eosinophils), smooth muscle and mucoal gland hypertrophy
Chronic bronchitis
· Chronic cough with production of sputum most days, for a least 3 months in 2 consecutive years
· Usually smoking/old patients
Emphysema
· Destruction/dilatation of the lung parenchyma distal to the terminal bronchioles
· Can be young (congenital conditions) or old
· Panacinar
o Uniform destruction of acinus (lower basal zones)
o A1AT deficiency
· Centriacinar
o Central/proximal respiratory tree (upper lobes/apices)
o Smokers
Bronchiectasis
· Permanent and abnormal dilatation of bronchi
· Associated with inflammation
· Congenital - Cystic fibrosis, severe immune deficiency
· Post-infectious (severe viral, bacteria, fungal pneumonia)
· Bronchial obstruction (tumour, foreign body)
· Complications
o Chronic infection with H. influenzae
o Secondary infection with:
§ Staph. aureus
§ Moraxella catarrhalis
§ Pseudomonas
o Right ventricular failure
o Amyloidosis
Cystic Fibrosis
· Autosomal recessive.
· Mutation in CFTR gene → hyperviscous secretions
· Complications:
o Bronchiectasis (recurrent infections - staph, H. influenzae, P. Aeruginosa, B. Cepacia)
o Pancreatic failure
o Sperm maturation defects
Restrictive pulmonary disease
Pulmonary oedema
· Causes:
o IHD
o Hypertension
o Valve disease
o Myocardial disease
· Consequences:
o Impaired pulmonary outflow
§ Congestion and oedema
o Reduced renal perfusion
§ Salt and water retention + ATN
o Reduced CNS perfusion (encephalopathy)
Pulmonary Fibrosis
· Laying down of fibrotic tissue in the lung parenchyma
· Most important restrictive pathology
o FEV1/FVC > 0.7
· Characteristic features:
o Progressive shortness of breath
o Cyanosis (+ clubbing)
o Fine end inspiratory crackles
Extrinsic allergic alveolitis / Hypersensitivity Pneumonitis - Immune reaction from inhalation of antigens (fungal, bacterial, animalprotein, chemical)
Occupation-related
• Farmer’s lung (thermophilic actinomycetes)
• Bird fancier’s lung (avian proteins)
Pathology - interstitial pneumonitis + non-caseating granulomas
Pneumoconoses / Inflammatory lung conditions caused by inhalation of mineral dusts.
Lag Period of up to 30 years
Over-reaction to deeply seated dust particles with peristent inflammation
Types
• Coal dust (coal miners)
Lung nodules (coal macules) + massive fibrosis
• Silicosis (mining, quarrying, glass making)
Nodular fibrosis
• Asbestosis (ship building, construction)
•Diffuse fibrosis
Autoimmune / Sarcoidosis
Non-caseating granulomas + multisystem disease
Rheumatoid arthritis
Lupus
Systemic sclerosis
Ankylosing spondylitis
Drugs / Causes pneumonitis (may → fibrosis)
Reversible with early recognition
• Bleomycin
• Amiodarone
Radiation / Well-recognised complication of therapy for:
• Primary Lung Tumours
• Breast Carcinoma
1-6/12 after therapy
Lung cancer
· Benign (rare)
o Hamartomas,
o Clear cell tumours
o Papillomas
o Fribromas
o Asymptomatic
· Malignant
o Non-small cell - 80%
§ Squamous cell
§ Adenocarcinoma
§ Large cell undifferentiated/alveolar cell
o Small cell (neuroendocrine) - 20%
· Local effects
o Bronchial obstruction → collapse
o Impaired mucus clearance →infections
o Invasion
o SVC, brachial plexus, oesophagus
o Extension through pleura/pericardium
o Pleuritis and pericarditis
o Lymphatic invasion → lymphangitis carcinomatosis
· Distant effects
o Peptide production
o ACTH
o ADH
o PTH-like (particular to squamous)
o Para-neoplastic syndromes
o Lambert-Eaton myaesthenic syndrome, acanthosis nigrians, dermatomyositis
o Metastases (common in bone, brain and liver)
Pneumothorax
· Spontaneous
o Primary - apical blebs
o Secondary - COPD, asthma, pulmonary fibrosis, lung cancer
· Acquired
o Traumatic
o Iatrogenic - central line insertion, pleural aspiration, barotraumas
Asbestos related lung-disease
· Pleural plaques (marker of exposure)
· Asbestosis (pulmonary fibrosis)
· Adenocarcinoma (lung cancer - particularly in smokers)
· Mesothelioma
o Tumor of mesothelial lining (pleural, pericardial, peritoneal)
o Epitheliod, sacromatoid, biphasic, desmoplastic
o Estimated peak of disease around 2020
Hepato-biliary pathology
Hepatic Failure
Clinical syndrome occurring when > 90% functional capacity of liver is lost
Acute Liver Failure
· Common causes
o Acute Viral Hepatitis (AST > 1000)
§ Hep. A/B/C, CMV/EBV
o Alcholic Hepatitis (AST < 300)
§ Raised GGT + MCV
o Drug-related Hepatitis
§ Paracetamol, NSAIDS, antibiotics
· Clinical Features
o Hepatic encephalopathy
o Irritability →sleep disturbance →disorientation → coma
o Coagulopathy
o Jaundice (conjugated)
o Infection (sepsis + multi-organ failure)
o Hepato-renal syndrome/hepato-pulmonary syndrome
Chronic Liver Disease
· Persistent liver damage > 6 months without resolution
o Progressive Fibrosis
o Cirrhosis
Cirrhosis
Whole liver involved with triad of:
· Fibrosis
· Nodules of regenerating hepatocytes
· Distortion of liver architecture
· Complications
o Hepatic failure (decompensation)
o Hepatocellular carcinoma
o Portal hypertension
o Ascites
o Porto-systemic shunts
o Oesophageal varices, haemorrhoids, caput medusa
o Splenomegaly (hypersplenism)
· Causes
Cause / Deficit / FeaturesAlcohol / Alcohol byproducts activate Hepatic Stellate Cells → Fibrosis
3 distinct pathologies
- Alcoholic Hepatitis
- Alcoholic Fatty Liver
- Alcoholic Cirrhosis
Viral hepatitis
Steatohepatitis / Non-alcoholic liver disease
Similar appearance but associated with metabolic syndrome
? Insulin resistance (reduced peripheral lipolysis)
Continuum
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis (may lead to cirrhosis)
Wilsonʼs disease / Disorder of ATPase Copper transport protein
Accumulation of copper in liver → hepatolenticular degeneration
AD transmission / Neurology + Kayser-Fleisher rings
Low caeruloplasmin + low copper
Haemochromatosis / HFE gene C282Y mutation → excessive GI absorption of iron
AR + manifests > 40 years old
Accumulation in multiple organs / Liver
– cirrhosis
– hepatocellular carcinoma
Heart
– Congestive cardiac failure
– Conducting defects and arrhythmia
– Constrictive pericarditis
Endocrine
– Diabetes
– Panhypopituitarism
– Hypogonadotropism
Joints
– Chondrocalcinosis
Loss of Libido
Alpha-1 anti-trypsin deficiency
Autoimmune / Middle aged women with co-existant autoimmune disease
High transaminases + raised IgG
ANA + anti-SM antibodies
Responds well to steroids
Primary biliary cirrhosis
· Intrahepatic bile ducts (cholangiocytes)
· Pruritus
· Raised ALP + GGT
· Anti-mitochondrial/IgM
Primary sclerosing cholangitis
· Sclerosis of Intra- and extrahepatic ducts
· Association with UC (75%)
· Isolated raised ALP
· Risk of cholangiocarcinoma
Hepatic Neoplasia
Benign Tumours
· Haemangioma
o Most common - 3% population
o Asymptomatic (incidental finding)
· Liver cell adenoma
o Young women on COC
Malignant Tumours
· Hepatocellular Carcinoma
o Develop on background of cirrhosis/chronic inflammation
o 1/3rd→ DNA mismatch repaid
· Cholangiocarcinoma
o Malignancy of intrahepatic bile ducts
o Non-specific presentation
o Jaundice, weight loss, pruritus, pain
o Present late with poor prognosis
Gallstones
· Types:
o Cholesterol (most common)
o Pigment (haemolytic states)
· Risk factors
o Female
o Forty
o Fat
o Fertile
o Fair
Annular Pancreas
· Failure of migration of the ventral bud
· Obstructs duodenum
· Presents in infancy with a similar picture to pyloric stenosis
Pancreas Divisium
· Incomplete fusion of the ventral and dorsal ducts
· Predisposes to
o Chronic Pancreatitis
o Pancreas Ca
Acute Pancreatitis
· Inflammatory condition of the pancreas
· Causes
o Gallstones (45%)
o Ethanol (25%
o Trauma
o Steroids
o Mumps/Infections
o Autoimmune
o Scorpion venom
o Hyperlipidaemia, hypercalcaemia
o ERCP
o Drugs
· Symptoms:
o Epigastric pain radiating to back
o Relieved by sitting forward
o Associated with vomiting
· Signs:
o Unwell
o Fever
o Tachycardia/pnoeia
o Jaundice
o Local/general peritonitis +/- shock and ileus
o Cullen’s Sign
o Grey-Turner’s signS
· Complications
o Respiratory: ARDS, atelectasis, pleural effusion
o Organ failure: myocardial depression
o DIC
o Metabolic: hypocalcaemia, hyperglycaemia, met acidosis
o Necrosis, pseudocyst , abscess, infection
Chronic Pancreatitis
· Repeated episodes of pancreatic inflammation leading to structural damage and fibrosis
· Results in exocrine and endocrine dysfunction
· Symptoms
o Wt loss
o Poor appetite
o Pain
o Exocrine dysfunction
o Endocrine dysfunction
· Signs
o Epigastric tenderness
o Erythema ab igne
Pancreatic Tumours
· M>F
· Elderly
· Western Countries
· Risk Factors
o Lifestyle: smoking, alcohol
o Toxin exposure: naphthylamine (dye industry), benzidine
o Disease states: chronic pancreatitis, diabetes
o Congenital: pancreas divisum
· Symptoms
o Anorexia
o Malaise
o Weight loss
o Chronic epigastric pain radiating to back
o Steatorrhoea
o Diabetes symptoms
· Signs
o Cachexia
o Lymphadenopathy
o Signs of EtOH use
o Painless obstructive jaundice
o Palpable gallbladder
o Hepatosplenomaegaly and ascites
o Thrombophlebitis migrans
o Marantic endocarditis
Pathology of the Gut
Achalasia
· Dysmotility disorder of the oesophagus
· Degeneration of Auerbach plexi
· Sequelae:
o Dysphagia (liquids and solids)
o Hypertrophy
o Squamous cell carcinoma
Hiatus Hernia
· Impaired lower
· oesophageal sphincter
· Reflux of gastric contents + oesophagitis
Reflux Oesphagitis/GORD
· Acidic gastric contents → lower oesophagus
· Risk factors:
o Increased IAP (obesity, posture, large meals, alcohol)
o Hiatus hernia
· Complications
o Peptic Stricture
§ Scarring and deformation → narrowing
o Barretts Oesophagitis (10%)
§ Columnar metaplasia
o Adenocarcinoma
Barrett’s Oesophagus
· Oesophageal columnar metaplasia