Cardiovascular Disease

HistopathologyNotes

Cardiovascular Disease

BP = CO x SVR

CO = HR x SV

Infarction

• Necrosis due to ischaemia

• Arterial
• MI
• Stroke
• Bowel infarction
• Acute limb ischaemia
• Venous
• PE
• Torsion of vascular pedicle
• Sigmoid volvulus
• Testicular torsion

Atherosclerosis

• Arterial wall thickening and loss of elasticity

Stages

• Endothelial cell injury
• Inflammatory response in vessel wall
• Oxidised LDL
• Formation of stable atherosclerotic plaque
• Vascular smooth muscle phenotype shift
• Complication of stenosis or plaque rupture

Risk Factors

• Non-Modifiable
• Age
• Sex
• Family history
• Others - Type A personality, oestrogendeficiency

• Modifiable
• Hypertension
• Diabetes Mellitus
• Smoking
• Hypercholesterolaemia
• Others - physical inactivity, lipoprotein Lp(a)

Complications

• Plaque-related Stenosis(angina, intermittent claudication)
• Plaque rupture
• Thrombosis (MI, stroke, acute limb ischaemia)
• Embolism (MI, stroke, acute limb ichaemia)
• Weakening of vessel wall (AAA)

Acute Coronary Syndrome

• Unstable angina
• No cardiac damage (normal tropnin)
• NSTEMI/STEMI
• Cardiac damage (raised tropnin)

Acute Limb Ischaemia

• Thrombosis (60%)
• Hx of claudication/rest pain
• Onset over hours
• Signs of chronic vascularinsufficiency
• Hard arteries
• No bruits

• Embolism (30%)
• Recent MI, atrial fibrillation, aneurysm
• Onset over seconds
• No evidence of previous disease
• Soft artery
• Bruits

Hypertension

• 140/90 (based upon additional risk factors)
• 160/100 (absolute)

• Primary (essential) - 95%
• Idiopathic

• Secondary
• Renal disease
• Endocrine disease
• Pregnancy
• Drugs

Sequalae

• HTN retinopathy
• CVA
• ↑ Glucose levels
• HTN encephalopathy
• MI
• HTN Cardiomyopathy
• HTN Nephropathy

Cardiac Failure

A syndrome caused by anyabnormality of the heart that may becharacterised by a set of haemodynamic,

neural, and endocrine abnormalities

LVF

• Causes:
• IHD
• Hypertension
• Valve disease
• Myocardial disease
• Consequences:
• Impaired pulmonary outflow
• Congestion and oedema
• Reduced renal perfusion
• Salt and water retention + ATN
• Reduced CNS perfusion (encephalopathy)

RVF

• Causes:
• Left-sided heart failure (Congestive)
• Chronic Lung Pathology - CorPulmonale
• Consequences:
• Portal, systemic and peripheral congestion
• Tricuspid regurgitation
• Renal congestion (R > L)

Cardiomyopathy

Causes / Features
Hypertrophic / 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 mycoytescausingdilation + 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.gcalcific aortic stenosis)

Stenosis

• Pressure overload + hypertrophy
• Develops slowly

Regurgitation

• Volume overload
• Develops quickly or slowly

Complications

• Hypertrophy
• LVF
• Worsening of IHD, heart failure
• Pro-arrhthymia
• Dilation
• Mitral and atria
• Risk of Endocarditis

Types / Pathogenesis / Features
Rheumatic Fever / Acute inflammatory disorder of children (5-15)
Post-streptococcal (5 weeks) / Foci of fibrinoid necrosis → Aschoff Bodies, Fibrinouspericarditis, 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
• CO2 - Compensation (pCO2 - normal/low)
• O2 – No compensation

Type II respiratory failure

• COPD, neuromuscular disease, severe acute asthma
• Hypoventilation
• Impaired transfer of Co2 and O2 (pCO2 elevated)

Pulmonary Embolus

• 95% of PE from deep vein thrombi in legs/pelvis
• Large - Instant death (acute corpulmonale)
• 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:
• Left-sided heart failure (congestive)
• Chronic lung pathology → corPulmonale
• Consequences:
• Portal, systemic and peripheral congestion
• Tricuspid regurgitation
• 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
• Overinflated, patchy atelectasis, mucus plugs
• Microscopic
• 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
• Uniform destruction of acinus (lower basal zones)
• A1AT deficiency
• Centriacinar
• Central/proximal respiratory tree (upper lobes/apices)
• 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
• Chronic infection with H. influenzae
• Secondary infection with:
• Staph. aureus
• Moraxellacatarrhalis
• Pseudomonas
• Right ventricular failure
• Amyloidosis

Cystic Fibrosis

• Autosomal recessive.
• Mutation in CFTR gene → hyperviscous secretions
• Complications:
• Bronchiectasis(recurrent infections - staph, H. influenzae, P. Aeruginosa, B. Cepacia)
• Pancreatic failure
• Sperm maturation defects

Restrictive pulmonary disease

Pulmonary oedema

• Causes:
• IHD
• Hypertension
• Valve disease
• Myocardial disease
• Consequences:
• Impaired pulmonary outflow
• Congestion and oedema
• Reduced renal perfusion
• Salt and water retention + ATN
• Reduced CNS perfusion (encephalopathy)

Pulmonary Fibrosis

• Laying down of fibrotic tissue in the lung parenchyma
• Most important restrictive pathology
• FEV1/FVC > 0.7
• Characteristic features:
• Progressive shortness of breath
• Cyanosis (+ clubbing)
• Fine end inspiratory crackles

Extrinsic allergic alveolitis / Hypersensitivity Pneumonitis - Immune reaction from inhalation of antigens (fungal, bacterial, animal
protein, chemical)
Occupation-related
• Farmer’s lung (thermophilicactinomycetes)
• Bird fancier’s lung (avian proteins)
Pathology - interstitial pneumonitis + non-caseatinggranulomas
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-caseatinggranulomas + multisystem disease
Rheumatoid arthritis
Lupus
Systemic sclerosis
Ankylosingspondylitis
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)
• Hamartomas,
• Clear cell tumours
• Papillomas
• Fribromas
• Asymptomatic
• Malignant
• Non-small cell - 80%
• Squamous cell
• Adenocarcinoma
• Large cell undifferentiated/alveolar cell
• Small cell (neuroendocrine) - 20%

• Local effects
• Bronchial obstruction → collapse
• Impaired mucus clearance →infections
• Invasion
• SVC, brachial plexus, oesophagus
• Extension through pleura/pericardium
• Pleuritis and pericarditis
• Lymphatic invasion → lymphangitiscarcinomatosis

• Distant effects
• Peptide production
• ACTH
• ADH
• PTH-like (particular to squamous)
• Para-neoplastic syndromes
• Lambert-Eaton myaesthenic syndrome, acanthosisnigrians, dermatomyositis
• Metastases (common in bone, brain and liver)

Pneumothorax

• Spontaneous
• Primary - apical blebs
• Secondary - COPD, asthma, pulmonary fibrosis, lung cancer
• Acquired
• Traumatic
• 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
• Tumor of mesothelial lining (pleural, pericardial, peritoneal)
• Epitheliod, sacromatoid, biphasic, desmoplastic
• 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
• Acute Viral Hepatitis (AST > 1000)
• Hep. A/B/C, CMV/EBV
• Alcholic Hepatitis (AST < 300)
• Raised GGT + MCV
• Drug-related Hepatitis
• Paracetamol, NSAIDS, antibiotics

• Clinical Features

• Hepatic encephalopathy
• Irritability →sleep disturbance →disorientation → coma
• Coagulopathy
• Jaundice (conjugated)
• Infection (sepsis + multi-organ failure)
• Hepato-renal syndrome/hepato-pulmonary syndrome

Chronic Liver Disease

• Persistent liver damage > 6 months without resolution
• Progressive Fibrosis
• Cirrhosis

Cirrhosis

Whole liver involved with triad of:

• Fibrosis
• Nodules of regenerating hepatocytes
• Distortion of liver architecture

• Complications

• Hepatic failure (decompensation)
• Hepatocellular carcinoma
• Portal hypertension
• Ascites
• Porto-systemic shunts
• Oesophageal varices, haemorrhoids, caput medusa
• Splenomegaly(hypersplenism)

• Causes

Cause / Deficit / Features
Alcohol / Alcohol byproducts activate HepaticStellate 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-trypsindeficiency
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 sclerosingcholangitis

• Sclerosis of Intra- and extrahepatic ducts
• Association with UC (75%)
• Isolated raised ALP
• Risk of cholangiocarcinoma

Hepatic Neoplasia

Benign Tumours

• Haemangioma
• Most common - 3% population
• Asymptomatic (incidental finding)
• Liver cell adenoma
• Young women on COC

Malignant Tumours

• Hepatocellular Carcinoma
• Develop on background of cirrhosis/chronic inflammation
• 1/3rd→ DNA mismatch repaid

• Cholangiocarcinoma
• Malignancy of intrahepatic bile ducts
• Non-specific presentation
• Jaundice, weight loss, pruritus, pain
• Present late with poor prognosis

Gallstones

• Types:

• Cholesterol (most common)
• Pigment (haemolytic states)

• Risk factors

• Female
• Forty
• Fat
• Fertile
• 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
• Chronic Pancreatitis
• Pancreas Ca

Acute Pancreatitis

• Inflammatory condition of the pancreas
• Causes

• Gallstones (45%)
• Ethanol (25%
• Trauma
• Steroids
• Mumps/Infections
• Autoimmune
• Scorpion venom
• Hyperlipidaemia, hypercalcaemia
• ERCP
• Drugs

• Symptoms:

• Epigastric pain radiating to back
• Relieved by sitting forward
• Associated with vomiting

• Signs:

• Unwell
• Fever
• Tachycardia/pnoeia
• Jaundice
• Local/general peritonitis +/- shock and ileus
• Cullen’s Sign
• Grey-Turner’s signS

• Complications

• Respiratory: ARDS, atelectasis, pleural effusion
• Organ failure: myocardial depression
• DIC
• Metabolic: hypocalcaemia, hyperglycaemia, metacidosis
• Necrosis, pseudocyst , abscess, infection

Chronic Pancreatitis

• Repeated episodes of pancreatic inflammation leading to structural damage and fibrosis
• Results in exocrine and endocrine dysfunction
• Symptoms

• Wt loss
• Poor appetite
• Pain
• Exocrine dysfunction
• Endocrine dysfunction

• Signs

• Epigastric tenderness
• Erythemaabigne

Pancreatic Tumours

• M>F
• Elderly
• Western Countries
• Risk Factors
• Lifestyle: smoking, alcohol
• Toxin exposure: naphthylamine (dye industry), benzidine
• Disease states: chronic pancreatitis, diabetes
• Congenital: pancreas divisum
• Symptoms

• Anorexia
• Malaise
• Weight loss
• Chronic epigastric pain radiating to back
• Steatorrhoea
• Diabetes symptoms

• Signs

• Cachexia
• Lymphadenopathy
• Signs of EtOH use
• Painless obstructive jaundice
• Palpable gallbladder
• Hepatosplenomaegaly and ascites
• Thrombophlebitismigrans
• Maranticendocarditis

Pathology of the Gut

Achalasia

• Dysmotility disorder of the oesophagus
• Degeneration of Auerbachplexi
• Sequelae:
• Dysphagia(liquids and solids)
• Hypertrophy
• Squamous cell carcinoma

Hiatus Hernia

• Impaired lower
• oesophageal sphincter
• Reflux of gastric contents + oesophagitis

Reflux Oesphagitis/GORD

• Acidic gastric contents → lower oesophagus
• Risk factors:
• Increased IAP (obesity, posture, large meals, alcohol)
• Hiatus hernia
• Complications
• Peptic Stricture
• Scarring and deformation → narrowing
• BarrettsOesophagitis (10%)
• Columnar metaplasia
• Adenocarcinoma

Barrett’s Oesophagus

• Oesophageal columnar metaplasia
• Adaptive response to acidic damage
• Dx at endoscopy and confirmed by histology
• Pre-malignant potential

Oesophageal Carcinoma

• Presents late
• Malaise, weight loss
• Progressive dysphagia

• Squamous Cell (squamous differentiation)
• Smoking, alcohol, achalasia
• Middle-third

• Adenocarcinoma(glandular differentiation)
• Barrett’s oesophagus
• Lower third

Gastritis

• Causes

• Infection (H. Pylori)
• Autoimmunity (→ Pernicious Anaemia)
• Drugs (NSAID’s)
• Alcohol

H. pylori

• Micro-aerophilic Gram-ve bacterium
• Infects gastric-type mucosa
• Predilection for antral colonisation
• Increase in Gastrin production increases acid production
• Faeco-oral and oro-oral transmission

Peptic Ulcer Disease

• Full thickness breaches in mucosa
• Solitary
• Common sites:
• Gastric antrum
• 1st part of duodenum
• Complications
• Haemorrhage (posterior)
• Haematemesis
• Perforation (anterior)
• Abdominal pain + peritonitis
• Stricture (post-healing)
• Gastric outflow obstruction

Gastric Tumours

Adenocarcinomas

• Intestinal
• Inflammation → metaplasia → dysplasia sequence
• H. Pylori-related

• Diffuse
• Normal mucosa
• SIignet ring cells
• Highly infiltrative + aggressive (linitisplastica)

Gastric lymphoma

• No lymphoid tissue normally
• H. Pylori → migration hyper-stimulation of B lymphocytes
• Can lead to Marginal cell lymphoma
• Responds to antibiotics

Leiomyomas/leimyosarcomas

• Benign/malignant tumour of muscle
• Also affects:
• Uterus (fibroid)
• Oesophagus (rare <1% oesophageal tumours)
• Skin (solitary cutenous, multiple, angioleiomyomas)

Stromal Tumours

• Connective tissue origin
• Features:
• Over-expression of tyrosine kinase KIT
• Exophytic
• May be treated with Imatinib

Coeliac disease

• Gluten-sensitive enteropathy
• Inappropriate T cell driven inflammation → lymphocytic enteritis
• Malabsorption (iron + folate)
• Clinical Features
• Adulthood
• Anaemia
• GI sx - discomfort, altered bowel habit (IBS-like)
• Failure to thrive in kids/adolescents
• Diagnosis

• Antibody serology
• IgAendomysial
• IgGantigliadin
• IgA tissue transglutaminase
• Small bowel biopsy (distal duodenum)

• Complications

• Osteopaenia/osteoporosis
• Enteropathy-associated T cell lymphoma (EALT)
• Deterioration despite good diet control
• Extremely destructive (obstruction/perforation)

Inflammatory Bowel Disease

• Excess wall-based inflammatory activity leading to relapsing and remitting disease

Ulcerative Colitis / Crohns Disease

• Large intestine only (back-wash ileitis)
• Extends proximally from the rectum
• Mucosal layer only
• Pathology:
• Diffuse mucosal inflammation
• Crypt abscess
• Complications
• Dilatation + perforation
• Due to involvement of muscle coat (transverse)
• Adenocarcinoma
• Flat, ill-defined tumours (not usually polyps)
• Endoscopic surveillance

/

• Any part of bowel (small bowel/colon)
• Lesions “skip”
• Full thickness involvement
• Pathology:
• Patchy full thickness inflammation with small lymphoic aggregates
• Non-caseatinggranulomas
• Deep fissuring ulcers
• Complications
• Obstruction
• Fistulae formation
• Peri-anal disease

• Extra-intestinal manifestations of IBD

• Arthritis (ankylosingspondylitis)
• Erythemanodosum
• Uveitis

Colo-rectal carcinoma

• Aetiology
• Western lifestyle: low-fibre diet, smoking
• Other disease states:
• Familial adenomatouspolyposis (APC)
• Hereditary non-polyposis coli (MLH1)
• Peutz-Jeghers syndrome
• IBD
• Gastrectomy
• Multiple mutations required for Adenoma →carcinoma
• Mutation →spatial reorganisation of crypts
• Proliferative element accumulated superficially
• Exposure of element to luminal carcinogens→ further mutations
• Complications
• Chronic blood loss (IDA)
• Obstruction
• Perforation

Pathology of the Nervous System

Cerebrovascular Accident/Stroke

• Sudden onset neurological deficit lasting > 24 hours
• Attributable to a vascular cause
• Infarction (80%)
• Haemorrhage (20%)

Infarction

• Aetiology

• In-Situ Thrombus
• Rare
• Thrombo-embolism
• Internal carotid artery
• Proximal Intracerebral artery
• Left atrium (AF)
• Left ventricle/valves (post-MI, endocarditis)

Haemorrhage

• Hypertension
• Charcot-Bouchard aneurysms
• Basal ganglia + thalamus
• Cerebral amyloidangiopathy(10%)
• Age-related (not to other amyloid disease)
• Border of white matter
• AV malformation (young patients)

Head Trauma

Location / Injury / Clinical Features / Management
Extra-dural / Outside the dura
mater / Disruption of arteriesfrom the middlemeningeal artery / LOC → lucid period →
deterioration
(coning) → death / CT (lens shapedhaematoma)
Neurosurgicaldrainage
Sub-dural / Betweenarachnoid anddura / Rupture of bridgingvein / Insidious onset
(alcoholics/elderly)
Headache, sensory and/or motor Sx / Inv: CT
Rx: Surgicalevacuation of
haematoma
Subarachnoid / Under arachnoid / Trauma or ruptured Berry aneurysm / Sudden onsetHeadacheMeningism / Inv: CT, cerebral
angiography
Rx: Conservate/
Surgery (clipping/
embolisation)
Intra-cerebral / Within braintissue / Damage to brain
substance / Compressive and
localising signs / Surgical drainage

Traumatic Parenchymal Injury

• Concussion
• Transient LOC with recovery over days (RAS damage)
• Diffuse axonal injury
• Stretching and tearing of white matter
• Post-traumatic dementia and veg. states
• Contusion
• Haemorrhages on superficial brain surface
• Coup and contracoup
• Traumatic intracerebral haemorrhage
• Deep contusions
• Associated with diffuse axonal injury + oedema + subarachnoid haemorrhage

Cerebral Oedema

• Causes

• Idiopathic
• Generalised
• Hypoxia
• Metabolic disturbance
• Trauma
• Hypertension
• Localised
• Ischaemia
• Haematomas
• Tumours

• Mechanisms

• Acute- cytotoxicity
• Damaged cells swell and leak Na/K.
• Chronic - vasogenic activity
• Cerebral vessel become leaky and fluid leaves

• Clinical features
• Headache (stretch of receptors around intracranial blood vessels)
• Worse in morning + on movn
• Vomiting (stimulation of centres in pons/medulla)
• Papilloedema(swelling of optic disc)
• Complications
• Vascular damage
• Central retinal vein compression → papilloedema
• Haemorrhage/infarct
• Intracranial Nerve damage (III/VI)
• Obstruction to CSF flow
• Herniation

Benign Intracranial Hypertension

• Pseudotumourcerebri
• Unknown cause:
• Obese females
• Headache + papilloedema
• No focal neurology

Brain Tumours