Cardiovascular pathology Dr D S O

1
Cardiovascular pathologyDr D S OBriain October
2005

• Systemic pathology 6 lectures
• Topic 2-5 min discussion, then summary panel
• Segments
• ischaemic heart disease (24 panels)
• Rheumatic fever (3), Congenital heart disease
  (4), other valve diseases (4), infective
  endocarditis (3)
• Hypertension (10)
• myocarditis (2), cardiomyopathy (4), transplants
  (4)
• pericardium (2) tumours (2)
• Chemical pathology (Dr Crowley)
• atherosclerosis (20), aneurysms (4)
• vasculitis (7), vessels (3)

2
Ischaemic Heart Disease

• Imbalance in the supply and demand for oxygen
  (also for nutrients and for removal of
  metabolites) in cardiac muscle.
• Increased demand Exercise, emotion
• Decreased supply
• Reduced oxygen (anaemia, cyanosis, carbon
  monoxide, cigarettes).
• Reduced coronary flow (atheroma, thrombus,
  spasm, shock).

3
Ischaemic Heart Disease Epidemic

• Causes 80 of cardiac mortality
• Peaked in US in 1960s, 40 decline since
• Different patterns in some Western countries
• Cause of decline Changing lifestyle (diet,
  smoking, exercise)
• Better therapy (CCU, thrombolysis, arrhythmia
  therapy, CABG, angioplasty)

4
Atherosclerotic Coronary Artery Disease
Distribution

• Narrowing of greater than 75 is clinically
  significant
• In 1/3 of patients one vessel is involved, in
  1/3, two vessels and in 1/3, three vessels.
• Sites Proximal 2 cm of LAD and circumflex,
  proximal 1/3 of right coronary artery.
• Less frequent Secondary diagonal, obtuse,
  marginal branches and posterior descending
  artery.
• Rare Intramyocardial branches

5
Atherosclerotic Coronary Artery Disease
Clinical Syndromes

• Silent Infarct
• Angina Pectoris
• Myocardial Infarct
• Chronic Ischaemic Heart Disease
• Sudden Death

6
Angina Pectoris

• Stable Pain with exercise, emotion or other
  increases in demand. ST segment
  depressedsubendocardial ischaemia
• Prinzmetal Rest pain, ST segment raised
  transmural ischaemia. Due to spasm, (? cause
  vasoconstrictive humoral factors, mast cells,
  nerves atherosclerosis usually present.)
• Unstable Pain, increasing in duration and
  severity with less effort or at rest, (also
  called preinfarction angina or acute coronary
  insufficiency). Caused by plaque enlarging,
  fissured, ulcerated, ruptured, vasospasm,
  platelet aggregation and activation

7
Atherosclerotic Coronary Artery DiseaseVascular
obstruction

• Platelets Plaque rupture (platelets adhere and
  become activated), thrombus forms (microemboli
  may occur), release of histamine, 5HT,
  thromboxane
• Vasospasm Demonstrated angiographically,
  rarely causes infarct in absence of atheroma, may
  rupture plaque, role of nerve supply and
  thromboxane
• Other Emboli, trauma, arteritis (SLE, PAN,
  etc), cocaine (arrhythmia, spasm), Haemodynamic
  effects (shock, coronary sinus obstruction).

8
Myocardial Infarct - Coronary Artery Lesions

• 90 of infarcts are supplied by an artery which
  has a thrombus over an ulcerated or fissured
  plaque
• Platelets activated aggregate to form thrombus
  (embolus) vasospasm, occlude. Deaths under 4
  hours 90 have thrombus over 12 hours 60
  have thrombus (thrombolysis)
• 10 without thrombus (usually have severe
  atherosclerosis) Spasm, platelet aggregates,
  emboli (mural thrombus, endocarditis,
  paradoxical), arteritis, cocaine, tachycardia or
  arrhythmia

9
Evolution of infarct

• 4 hours No morphological changes (subtle
  ultrastructural changes).
• 8 hours Oedema, myocytolysis, contraction band
  necrosis, wavy fibres.
• 24 hours Grossly pale, acute inflammatory
  infiltrate.
• Days Infarct becomes clearly defined grossly,
  centre softens, a hyperaemic rim appears,
  granulation tissue appears.
• Weeks Organisation proceeds leaving an organised
  scar by about six weeks.

10
Myocardial Infarct, Morphology

• Experimentally 20 minutes of occlusion
  ischaemic necrosis begins in the subendocardium
  (least collaterals and vessels most compressible)
• Infarct size Proportional to extent and duration
  of ischaemia, collateral supply, metabolic
  demands may be transmural or subendocardial.
• Site Left ventricle (If adjacent, right
  ventricle is involved in 25, adjacent atrium in
  5), isolated right ventricle in 1 (usually
  following marked right ventricle hypertrophy and
  strain).
• Distribution LAD (50) Anterior 2/3 septum,
  anterior wall, apex. RCA (35) Posterior wall and
  septum.
• LCA (15) Lateral left ventricular wall
• Infarcts are usually single may extend
  (retrograde thrombus, vasospasm, arrhythmia),
  reperfusion injury.

11
Cardiac Enzymes

• Creatine Kinase
• MB isoenzyme specific for heart
• Rises 4-8h, peaks 18h, falls 2-3d
• Troponin T or I
• Similar start, remain for 7-10d

12
Myocardial Infarct, Clinical

• Asymptomatic (15).
• Symptomatic (60). Sudden pain, crushing
  character, retrosternal, radiation (left
  shoulder, arm, jaw), associated sweating, nausea,
  vomiting, dyspnoea, indigestion.
• Sudden death (25).
• ECG new Q waves, ST and T wave abnormalities,
  arrhythmias, evolving pattern, 20 are
  non-specific or silent.
• Enzymes Soluble cytoplasmic enzymes (CK 4h-4d,
  Troponin I and T 4h-10d, AAT 8h-4d, LDH 1d-14d),
  LDH and CK isoenzyme patterns.
• Image Echo (mural dyskinesia), Angiography,
  perfusion scintography, MRI.

13
Effects of Myocardial Infarction

• Decompensation Muscle is dead, injured,
  stunned, disorganised,
• Infarct dyskinesia aneurysm, mural thrombus,
  embolism.
• Infarct rupture tamponade, septal shunt.
• Papillary muscle infarct or rupture (mitral
  valve dysfunction)
• Arrhythmias provoked in injured tissue.
• Haemorrhagic pericarditis.

14
Myocardial infarct complications

• Uncomplicated (15)
• Sudden death (25)
• Arrhythmia (sinus brady-, tachy-cardia,
  ventricular tachycardia, PVC, V fibrillation,
  asystole, block)
• Left ventricular failure (60)
• Pump failure (40 of myocardium damaged)
• Shock (10)
• Rupture (free wall, septum, papillary muscle)
• Thromboembolism
• Mortality 35 in one year (50 sudden, 25 in
  hospital. 10 die each subsequent year.

15
Percutaneous Transluminal Coronary Angioplasty

• Mechanisms
• Plaque compressionredistribute soft contents
  (most human plaques are hard)
• Plaque fracturebreaking, cracking, splitting
• healing/repair may change diameter
• Fracture with intimal flaps and localised
  medial dissection
• Stretching of plaque-free wall (70 of all, 24
  severe plaques, are eccentric)
• Stretching of concentric diseased wall

16
Percutaneous Transluminal Coronary
Angioplastycomplications

• Early closure
• Spasm
• Thrombus
• Dissection with large intimal flap
• Relaxation of overstreched wall of eccentric
  plaque
• Subintimal bleed (concurrent thrombolysis)
• Late chronic stenosis (17-47)
• Fibrocellular intimal proliferation
  (platelets,thromboxane A2,GFmyofibroblast and
  endotherial proliferation)
• (This also occurs in the left main artery
  (local injury or extension)
• Elastic recoil of plaque-free wall or recoil of
  concentric lesion
• Progression of plaque

17
Myocardial Infarct, Demography

• Age (only 5 under 40)
• Male (risk x 6 under 45, less when older)
• Smoker (risk x 5, proportional to number smoked)
• Other personality (type A increased risk),
  exercise and moderate alcohol protect
• Western countries risk was increased, now falling

18
Chronic Ischaemic Heart Disease

• Insidious congestive cardiac failure (possibly
  remote myocardial infarct or angina)
• Morphology Brown atrophy, patchy fibrosis, old
  infarcts
• Findings possibly left ventricular dilation,
  murmur, calcification
• ECG Normal, bundle branch block or non-specific
  changes

19
Sudden Cardiac Death

• Ischaemic heart disease (at least 75 stenosis),
  occluding thrombus in 1/2, new infarct in 1/4,
  old infarct in 1/3
• Other coronary artery disease anatomic
  anomolies, embolism, arteritis, dissection
• Myocardial disease hypertrophic obstructive
  cardiomyopathy, right ventricular dysplasia,
  myocarditis, amyloid, sarcoid
• Valve disease aortic valve stenosis, floppy
  mitral valve infective endocarditis.
• Conduction defects
• Electrolyte abnormalities

20
Congestive Cardiac Failure

• State resulting from impaired cardiac function
  and resulting in insufficient output for the
  metabolic requirements of tissues and organs
• Excess Load.
• B) Decreased pumping ability.
• Muscle fibre
• a) death
• b) dysfunction (decreased adrenergic drive,
  decreased receptor density, decreased calcium
  (excitation, contraction, coupling), altered
  mitochondrial and ATP-ase function, vasospasm of
  microcirculation.
• Decreased output - Forward failure.
• Damming back - Backward failure.

21
Cardiac Failure - Compensation

• Dilation produces increased force of contraction
  and stroke volume (Starling)
• Hypertrophy
• Increased blood volume
• But increased muscle mass and blood volume
  require more work excess dilation reduced
  efficiency
• No morphological difference between compensated
  and non-compensated heart look for hypoxic and
  congestive effects remote from the heart

22
Left Ventricular Failure

• Heart Hypertrophy and dilation of left
  ventricle (except mitral stenosis)
• Lungs Congestion, oedema of lung and pleural
  space, dyspnoea, orthopnoea, paroxysmal nocturnal
  dyspnoea, cough with frothy blood-tinged sputum
• Kidney Decreased perfusion (ischaemic tubular
  changes), renin angiotensin aldosterone system
  (increased NaCl, H20, ECF and blood volume)
• Brain Hypoxia irritable, decreased
  concentration and attention span, stupor, coma

23
Right Ventricular Failure

• A) Secondary to left ventricular failure
• B) Cor pulmonale, cardiomyopathy, constrictive
  pericarditis, tricuspid and pulmonary valve
  disease
• Liver Enlarged, chronic passive congestion
  (nutmeg), if severe central necrosis with
  fibrosis result in cardiac sclerosis (cardiac
  cirrhosis)
• Spleen Enlarged, congested, dilated sinusoids
  and fibrotic walls
• Kidney Congested
• Subcutis Oedema, anasarca
• Pleura Effusion (especially on right)
• Portal System Congestion of GIT, spleen ascites

24
Heart Failure
Organ LV Failure RV Failure Effect
Lung Oedema, cough, dyspnoea.
Kidney Fluid retention, decreased perfusion.
Brain Hypoxia.
Liver - Enlarged, congested.
Spleen - Enlarged, congested.
Portal - Ascites, GIT congestion.
Subcutis - Oedema.
25
Cor Pulmonale

• Right ventricular enlargement secondary to
  disordered structure or function of lungs
• Causes
• Lung parenchymal disease COAD, pulmonary
  fibrosis, cystic fibrosis
• Vascular disease pulmonary embolism, vasculitis
• Chest disorders Kyphoscoliosis, obesity,
  neuromuscular disorders
• Effect Narrowing of pulmonary vascular bed
  (hyperviscosity-polycythemia)
• Pulmonary hypertension -gt cor pulmonale (acute
  due to pulmonary embolism-or chronic). Right
  ventricular wall hypertrophies then dilates and
  fails

26
Rheumatic fever

• Acute recurrent inflammation associated with
  reaction to streptococcal infection. Occurs 1-5
  weeks after Group A, ß haemolytic streptococcal
  infection, mainly children (5-15 years)

27
Rheumatic Fever, Jones Criteria

• Major criteria of Jones
• Polyarthritis sequential involvement of large
  joints
• Erythema marginatum
• Subcutaneous nodules
• Sydenham's chorea rapid purposeless movements.
• Carditis
• Also (minor criteria) fever, arthralgia,
  previous rheumatic fever, prolonged PR interval,
  acute phase reactants (ESR, CRP or WCC increased)
  
• Jones (AHA) 2 major or 1 major and 2 minor
  criteria high probability of rheumatic fever.
• Recent streptococcal infection increases
  probability

28
Rheumatic Fever, Pathogenesis

• 1. Follows streptococcal infection but lesions
  sterile
• 2. Streptococcal antibodies anti streptolysin 0
  (AS0) hyaluronidase
• 3. Most frequent after severe streptococcal
  infections
• 4. Recur with repeated streptococcal infection
• 5. 90 decline in incidencebetter living
  conditions, antibiotics, organism has changed.
• 6. Individual susceptibility genetic.

29
Rheumatic Fever, Pathogenesis

• Aetiology
• Cross reaction
• Hyaluronate of humansstreptococcal capsule.
• Streptococcal membranemuscle sarcolemma
• Streptococcal M proteincardiac myosin
• Autoimmune - antiheart antibody (but ?
  cross reaction)
• Pathology Aschoff Body Fibrinoid necrosis
  surrounded by mononuclear cells with Anitschkew
  cells (with caterpillar nucleus), pericarditis
  (bread butter), myocarditis, endocarditis
  (verrucae on lines of closure) McCallum's
  patches. Heal by scarring - distort valve

30
Rheumatic Fever Cardiac involvement

• Acute - in 2/3 of children, 1/3 of adults.
• Pericarditis, arrhythmias (atrial fibrillation),
  prolonged PR interval, auricular thrombus,
  cardiac dilation (MI murmur). Valve involvement
  (MI, AI), (death 1))
• Chronic - if first attack severe or when very
  young.
• MV in 2/3, MV AV 1/4, TV (Few), PV rare
• Valve fibrosis, calcification, fused commissures
  (fish mouth) chordae.
• Mitral stenosis LA dilation, auricular thrombus,
  pulmonary congestion, RVH

31
Congenital Heart Disease - Varieties

• a) Shunts Chamber (or vessel) to chamber (or
  vessel).
• Right to left - Early cyanosis, clubbing,
  hypertrophic osteoarthropathy, polycythemia
  (cerebral thrombosis).
• Left to right - cyanose tardive. Increased
  pulmonary flow with vascular sclerosis,
  pulmonary hypertension, reversed flow (right to
  left). Shunt complication. paradoxical embolism,
  infected embolism, infective endocarditis.
• b) Obstruction Non-cyanotic. Failure to
  thrive, retarded development, intercurrent
  diseases of childhood.
• c) Malposition Ectopia, dextrocardia (isolated
  or other anomalies) situs inversus totalis
  (Kartagener sinusitis, bronchiectasis, immotile
  cilia).

32
Congenital Heart Disease - Early Cyanosis

• 1. Tetralogy of Fallot
• VSD, overriding aorta, right ventricular outflow
  obstruction, RVH.
• Outflow obstruction (infundibular, valve,
  supravalve) dictates severity.
• 2. Transposition (multiple combinations with
  atria, ventricles, vessels)
• Commonest RA-RV-Aorta
• Mixing essential ASD in all, most also have
  PDA, or VSD.
• 3. Truncus arteriosus
• Common aorta PA with three-cusped valve and
  coronary arteries
• Usually other cardiac defects
• 4. Tricuspid Atresia
• RV hypoplasia (often pulmonary valve and PA
  hypoplasia, ASD)

33
Congenital Heart Disease - Late Cyanosis

• 1. Ventricular septal defect
• Development of septum (week 5-6) common
  ventricle divided by muscular membranous septum
  
• 2. Atrial septal defect
• Development of septum (week 4) atrial canal
  closed by septum primum, (ostium primum). Valve
  effect allows RA-LA flow, closes at birth
• 3. Patent ductus arteriosus
• Ductus closes day 1-2 (High 02, low PGE)

34
Congenital Heart Disease - Late Cyanosis

• Ventricular septal defect
• Size dictates effect tiny to cor triloculare
  biatrium (pulmonary stenosis)
• Small 5mm (Roger), well tolerated, 50 close
  spontaneously, loud murmers thrill,
  endocarditis
• Large pulmonary hypertension, shunt reverses
• Atrial septal defect
• Ostium primum defect (5). Often Down's syndrome
• Ostium secundum (90). Often other defects
• Sinus venosus (5). Near SVC abnormal pulmonary
  vein return.
• Lutembacher syndrome ASD with pulmonary
  hypertension
• Patent ductus arteriosus
• 90 PDA isolated (important for survival in
  other forms of CHD).
• Machinery murmur, systolic thrill. LVH, dilated PA

35
Congenital Heart Disease - Obstructive

• 1. Coarctation of Aorta - systolic murmur
  thrill
• Preductal infants, (PDA) RVH with cyanosis
  of lower body
• Postductal adults (PDA in 50) hypertension
  in upper body insufficiency (claudication, cold)
  in lower body. Large collateral vessels
  intercostal, axillary, mammary with rib notching
• Survive to adulthood cardiomegaly, CCF,
  Infective aortitis, aortic rupture. Correct
  surgically
• 2. Pulmonary stenosis
• Atresia (poor outlook) or stenosis surgery,
  balloon valvuloplasty
• 3. Aortic stenosis
• systolic murmur thrill, usually isolated defect
  
• atresia (no survival) or stenosis -survival
  prolonged risk of sudden death, infection,
  haemodynamic effects

36
Other Valve Diseases

• Calcific aortic stenosis
• (Congenital stenosis) bicuspid (1 or
  population), rheumatic or normal valve becomes
  calcified - sclerotic, later stenotic.
• Result LVH, CCF angina, syncope, sudden death
• Mitral annular calcification
• asymptomatic, seen on imaging (rarely
  regurgitation, stenosis, arrhythmias, thrombi,
  infection)

37
Mitral valve prolapse

• Ballooned (floppy) valve with myxoid degeneration
  of valve fibrosa
• 7 of population, peak young females (in Marfan
  syndrome, abnormal fibrillin gene)
• Asymptomatic - mid systolic click late systolic
  murmur
• Minority chest pain, dyspnoea, fatigue,
  psychiatric symptoms
• Benign (Rarely infective endocarditis, mitral
  insufficiency, arrhythmias, emboli with
  infarction, sudden death)

38
Infective endocarditis

• Microbiological colonisation of valve. (Similar
  effect Colonise endocardium, aorta, aneurysms)
• Valve lesion
• Abnormal valves Rheumatic (especially small
  shunt, jet lesions), congenital (VSD, PDA,
  Fallot), mitral prolapse, calcific stenosis
  (bicuspid), prosthetic valves, catheters
• Normal valves
• Risk
• In neutropenia, immunodeficiency,
  immunosuppression, IVDA
• Seeding
• Infection, surgery, dentist, IVDA. trivial
  injury, transient gut or mouth seeding

39
Infective endocarditis

• Microbiological colonisation of valve. (Similar
  effect Colonise endocardium, aorta, aneurysms)
• Valve lesion
• Abnormal valves Rheumatic (especially small
  shunt, jet lesions), congenital (VSD, PDA,
  Fallot), mitral prolapse, calcific stenosis
  (bicuspid), prosthetic valves, catheters
• Normal valves
• Risk
• In neutropenia, immunodeficiency,
  immunosuppression, IVDA
• Seeding
• Infection, surgery, dentist, IVDA. trivial
  injury, transient gut or mouth seeding

40
Infective Endocarditis Organisms

• Organisms
• 65 streptococcal alpha haemolytic (viridens),
  bovis, faecalis
• 25 staphylococcus aureus.
• Others S. pneumoniae, GNB (E.Coli, N.
  gonorrhoea).
• 10 sterile.
• Precipitating factors
• agglutinating antibodies, adhesion factors,
  platelet -fibrin deposits on valve.

41
Infective Endocarditis Clinical

• Systemic fever, fatigue, weight loss, flu-like
  illness, chills.
• Murmur (changing in acute, absent in 10).
• Emboli subungual, retina (Roth spots) to
  brain, spleen, kidney (lung).
• Metastatic abscess (in acute) cerebral,
  meninges, renal.
• Renal Embolic infarct, focal or diffuse
  glomerulonephritis.
• Cardiac valve stenosis or incompetence, abscess,
  graft dehiscence, pericarditis

42
Infective endocarditis course

• Acute (days)
• virulent organism, large invasion, low
  resistance. On normal or prosthetic valve, IVDA,
  catheter. Large ulcerating vegetation, perforate,
  erode valve.
• Chronic (months)
• low virulence, partial healing.

43
Endocarditis, other forms

• Non-Bacterial thrombotic endocarditis
• 1-5mm, fibrin, on leaflet (lines of closure),
  sterile.
• marantic (chronic debilitating disease) or
  following catheter.
• Associated with DVT or pulmonary embolus
  (hypercoagulable states)
• Mucinous carcinomas (may secrete procoagulant)
• Complication (Rare), emboli, infarct, infection.
• Libman Sacks SLE (and antiphospholipid
  syndrome).
• 1-4mm, fibrin necrotic debris overlying
  fibrinoid necrosis.
• Anywhere in leaflet - MV TV, may be multiple.
  Also lesions in myocardium, pericardium and
  vessels

44
Malignant carcinoid syndrome

• Plaques of fibrous tissue on valve and
  endocardium of right ventricle outflow tract
• Syndrome
• Flushing, cramps, nausea, vomiting, diarrhoea
  (100)
• Cardiac disease (50)
• Asthma (33)
• Syndrome occurs in less than 1 of all carcinoids
  but in 10 of carcinoids with large hepatic
  metastases (rarely with ovarian or lung
  carcinoids)
• Mediators 5HT, kallikrein, bradykinin,
  histamine, prostaglandins
• Metabolism in liver, monoamine oxidases of lungs

45
Prosthetic valves

• Types
• A) Mechanical occluders
• B) porcine or bovine bioprostheses
• Complications in 5-10 (emboli 3, infection 1)
  per patient year
• Paravalvular leak
• Thromboembolism (anticoagulate mechanical
  valves) emboli, infection, obstruct movement of
  valve
• Infections at tissue interface (ring abscess),
  also at cusp in bioprosthesis
• Deterioration Bioprostheses, calcification and
  degeneration in 25
• Also Haemolysis, fibrous tissue ingrowth
  effecting function

46
Hypertension

• High blood pressure is common and asymptomatic,
• 25 of population gt140/90
• Incidence increases age, black, young males,
  older females
• More severe younger, blacks.
• Consequences Cardiac, cerebral and renal disease

47
Hypertension

• Types Primary 95
• Secondary 5 (renal, vascular, endocrine)
• Course Benign 95
• Accelerated (malignant) 5
• Compensated / decompensated.
• BP Cardiac output X peripheral vascular
  (arteriolar) resistance.
• Factors Blood volume, ECF volume, total body
  Na.
• Regulation renin-angiotensin-aldosterone
  system.

48
Terminology

• How to say
• "we have some ideas but we're not sure of the
  cause"
• primary
• ideopathic
• agnogenic
• cryptogenic
• essential

49
Essential Hypertension

• Pathogenesis Sodium retention and/or
  vasoconstriction
• Upper limit of the continuous variable of blood
  pressure
• Genetic factors (polygenic)
• Twin, sibling, familial, racial (blacks),
  animal (rat strains)
• Rarely single gene defects for aldosterone
  metabolism, sodium resorption
• Environment
• Exiled Chinese incidence increased behavior,
  stress, obesity, OCT
• Dietary sodium animal study (rats), remote
  peoples exposed to salt
• a) defect in Na excretion
• b) defect in cell membrane Na or Ca transport
• (?Ca - ?phosphorylation - ?response to
  vasoconstrictors)
• c) sympathetic response (stress, neurogenic
  factors)

50
Sodium Homeostasis

• Total body sodium regulates blood volume and
  cardiac output
• Influenced by
• Renin angiotensin system.
• ?Blood volume -?GFR - ?proximal tubule Na
  resorption.
• Atrial natriuretic factor inhibits (volume
  expansion -?GFR -?distal tubule Na resorption).
• Renal vasodepressors
• a) prostaglandins, b) kallikrein-kinin system, c)
  platelet activating factor.
• Vasoconstrictors angiotensin II, catechol
  amines, thromboxane, leukotriene, endothelin

51
Hypertension - Morphology

• Adaptive response to pressure or volume
  overload
• Myocyte cytoplasm and nucleus enlarged.
• New myofibrils, filaments, mitochondria,
  ribosomes
• (later degeneration, loss of myofibres, cell
  atrophy, interstitial fibrosis)
• Left ventricle Concentric hypertrophy
  (normal LV thickness 1.4 cm) dilates with
  decompensation

52
Hypertension - Effects

• Compensation - none.
• Decompensate - CCF
• Thick wall increases 02 requirement and
  diffusion distance
• Dilation - eventually overstretches fibres
• Myocyte degeneration and fibrosis - stiffness -
  impairs diastolic filling (stroke volume)
• Atherosclerosis

53
Benign nephrosclerosis

• Associations age, diabetes, hypertension.
• a) Arteriole walls thickened, hyaline, and lumen
  narrowed
• Hyaline plasma protein, lipids, basement
  membrane, intracellular matrix.
• b) Fibroelastic hyperplasia (interlobular
  arcuate arteries) - narrowing. Reduplication of
  elastic lamina, increased fibromuscular tissue in
  media.
• Secondary effects but may sustain aggravate
  hypertension.
• Effect - loss of tubules, interstitial fibrosis,
  damaged glomeruli, cortical narrowing, granular
  kidney surface, mild reduction in size of kidney,
• mild reduction in function and reserve.

54
Accelerated (malignant) hypertension - Clinical

• Medical emergency effects young, male, blacks
• CNS papilloedema, visual effects, encephalopathy
  headaches, nausea, vomiting, coma, fits
• CVS failure
• Renal proteinuria, haematuria (microscopic or
  gross), altered renal function, later failure
• 50 mortality in 3 months untreated - 50
  mortality in 5 years treated.
• Death - uremia (CNS or CVS disease)

55
Hyperplastic arteriosclerosis - Pathology

• De novo.
• On benign hypertension.
• On renal disease (GN, reflux, scleroderma )
• a) fibrinoid necrosis of arterioles (fibrin
  necrotising inflammation)
• b) hyperplastic arteriolitis (arterioles and
  interlobular arteries) onion-skinning with
  smooth muscle and collagen.
• Effect narrowed arterioles, necrotic
  glomeruli, thrombosed capillaries, ischaemic
  atrophy, infarction, high renin, endothelial
  injury (activated platelets, coagulation system
  - thrombus).

56
Secondary Hypertension (Mechanisms)

• Renal a) Renin increase renovascular
• b) Volume excess acute GN
• c) Mixed.
• Other Primary hyperaldosteronism ( blood
  volume)
• Phaeochromocytoma (vasoconstriction -
  (nor)adrenaline)
• Oral contraceptives (renin angiotensin)
• Periarteritis nodosa (renin angiotensin)

57
Renal Artery Stenosis

• Goldblatt. Hypertension proportional to
  constriction in one renal artery (Dog). Increased
  renin from JGA reverse with surgery or
  angiotension II antagonists. But secondary renal
  changes may lead to persisting hypertension
• 70 have atheromatous plaque at origin of artery
  (males, diabetes, age) 2/3 curable
• 30 fibromuscular dysplasia (females,young) 90
  curable Fibromuscular thickening of intima, media
  or adventitia multiple (or single) artery (or
  branches) unilateral (or bilateral)
• Morphology- In ischaemic kidney ischaemic
  changes, JGA hyperplastic, arterioles normal. In
  other kidney hypertensive changes.
• Clinical (Bruit) IVP small kidney, delayed
  function. Arteriogramvisualise stenosis,
  segmental beaded effect. Measure renal vein
  renin.

58
Myocarditis.

• Pathology Leucocyte infiltration and myocyte
  degeneration or necrosis.
• Heart is normal sized or
  enlarged.
• Patchy haemorrhagic foci,
  pale flabby myocardium.
• May involve one or several
  chambers.
• Normal peri- and
  endocardium.
• Clinical Asymptomatic.
• Fatigue, dyspnoea,
  palpitations, chest discomfort, fever.
• Arrhythmia.
• Sudden onset congestive
  cardiac failure, murmur (dilated AV valves).

59
Myocarditis, Aetiology.

• Viral Coxsachie A, B, ECHO, polio, influenza A,
  B, HIV. Occurs days to weeks after a respiratory
  or neurological infection (is occasionally
  primary). Cell mediated immunity (activated
  macrophages, CD8 lymphocytes), cells attack
  virus- containing myocytes.
• T. Cruzi South American Trypanosomiasis
  (Chagas disease). Myocarditis in 80, 10 die
  acutely.
• Trichinosis, Lyme disease (borrelia
  borgdorferi).
• Collagen Diseases Rheumatic fever, SLE.
• Drug Hypersensitivity (penicillin,
  sulphonamides), toxicity (diphtheria toxin,
  doxorubicin, catechol amine).
• Transplant rejection (cyclosporin is
  cytotoxic).
• Sarcoid.
• Giant cell, Fiedlers myocarditis.

60
Cardiomyopathy

• Non-inflammatory heart muscle disease of unknown
  cause.
• Exclude Inflammatory, hypertensive, congenital,
  valve and pericardial disease.
• Primary Dilated (congestive) more than 90
• Hypertrophic
• Restrictive (obliterative) rare
• Secondary.

61
Dilated (Congestive) Cardiomyopathy

• Heart weight increased, 4 chamber dilation,
  mural thrombi left ventricle (right ventricle,
  atria), valves and coronary arteries normal.
• Biopsy Fibre hypertrophy, focal fibrosis,
  endocardial thickening, foci of inflammatory
  cells, (normal in 1/4).
• Associations
• Alcohol Direct effect, thiamine deficiency,
  cobalt.
• Peripartum Nutritional, hypertensive,
  metabolic effects,
  
• occurs in poor multiparous women, regresses in
  50.
• Genetic dystrophin gene defect in 30
• Post Viral Evidence of remote myocarditis.
• Iron
• Arrhythmogenic RV dysplasia, familial (ch 14
  defect)
• Clinical Relentless congestive failure, 25 five
  year survival.

62
Hypertrophic Cardiomyopathy

• Also termed Asymmetric septal hypertrophy (ASH),
  Ideopathic hypertrophic subaortic stenosis
  (IHSS), Hypertrophic obstructive cardiomyopathy
  (HOCM)
• Heart enlarged, predominantly left ventricle,
  basal part (occasionally other chambers
  predominate), Asymmetric or symmetric,
  banana-shaped cavity, outflow obstructed by
  muscle (a disorder of diastole).
• Endocardial thickening, mural plaques, mitral
  valve thickening, Intramural coronary arteries.
• Microscopy Myocyte hypertrophy, disarray of
  cells and myofilaments in 50 of septum,
  interstitial fibrosis

63
Hypertrophic Cardiomyopathy

• Clinical
• Young adult
• Asymptomatic,
• Sudden death (with exercise)
• Dyspnoea, angina, dizzyness, congestive failure,
  atrial fibrillation, auricular thrombus, emboli,
  infected endocarditis (mitral valve).
• Pathogenesis Autosomal dominant (50)abnormal
  sarcomeric genes beta myosin heavy chain (in one
  third), cardiac troponin T, tropomyosin, myosin
  binding protein C
• Increased left ventricle wall thickness and
  decreased compliance decreases volume of
  ventricle (decreased stroke volume), obstructs
  mitral valve, and obstructs outflow, (dilation of
  congestive failure may improve function).

64
Restrictive Endocarditis

• Amyloid.
• Sarcoid.
• Radiation
• Endomyocardial fibrosis Children, young
  adults, Africa. Fibrosis in subendocardium and AV
  valves, mural thrombi frequent, restricts
  chamber inflow. ?Cause virus, malnutrition,
  excess 5HT in diet (bananas, plantain).

65
Heart transplantation

• 2500 transplants yearly, most for IHD and DCM, 5
  year survival 60-85
• Early (d 1-10) changes
• Immediate failure surgical factors, long
  ischaemia, pulmonary hypertensionhaemorrhage and
  oedema
• Hyperacute rejection incompatible
  matchingfibrin thrombi, polymorphs
• Reperfusion/ischaemia injury, (d 1-7, in
  all)focal necrosis, polymorphs

66
Heart transplantation

• Acute rejection, d 1-100 (Stanford
  Classification)
• Mild mild mononuclear infiltrate, perivascular
• Moderate Interstitial infiltrate, myocyte
  necrosis
• Severe Diffuse mixed infiltrate, myocyte
  necrosis, haemorrhage, vasculitis
• Resolving Diminished lymphocyte infiltrate,
  macrophages (haemosiderin) fibroblasts
• Resolved Mature focal scars
• Therapy rebiopsymild (cyclosporine), increase
  therapymild (azothioprine), moderate, severe

67
Pathology in Long-term Heart Transplants

• Rejectionrare after 3 months
• Graft atherosclerosis
• A) accelerated concentric narrowing of large
  and small arteries
• B) conventional atherosclerosis 40 in 5 years,
  diffuse not focal
• Cause immune mediated endothelial injury
  growth factors intimal proliferation (not
  related to acute rejection, age, history.
  ?related to steroid use, increased lipids, CMV
• Myocardium Myocyte hypertrophy related to
  duration of ischaemic period, Interstitial
  fibrosis related to ischaemia, cyclosporine
• Kidney cyclosporine interstitial fibrosis,
  atrophic tubules, segmental glomerulosclerosis
• Infections 60 of deaths in first year (CMV,
  toxoplasmosis, 50 seroconvert)
• Malignancy A) Skin basal and squamous
  carcinomas, other carcinomas
• B) Lymphoproliferative disorder in 10
  cyclosporine treated,
• EBV related, B-cell, high grade, extranodal
  (brain)

68
Pericardial fluid

• Effusion Non-inflammatory, low protein, few
  cells.
• Serous (congestive failure, hypoproteinaemia)
• Serosanguinous (trauma, resuscitation)
• Chylous (lymphatic rupture)
• Cholesterol
• Exudate Inflammatory, High protein, cells.
• Acute Serous, serofibrinous, fibrinous,
  purulent,
• suppurative, haemorrhagic, caseous.
• Chronic Obliterative, adhesive, constrictive.

69
Acute Pericarditis

• Serous usually non-bacterial (collagen diseases,
  uremia, tumour).
• Serofibrinous/fibrinous (Myocardial infarct,
  collagen disease, uremia, tumour, radiation less
  often bacterial, viral). Fibrin resolves or
  organises (adhesive pericarditis). Clinically
  Friction rub, pain, systemic febrile reaction,
  signs of congestive failure.
• Purulent/suppurative Bacterial, mycotic,
  parasitic direct spread from empyema, lobar
  pneumonia, endocarditis (rarely caused by virus,
  uremia, myocardial infarct.
• Haemorrhagic Tuberculosis, malignancy, cardiac
  surgery, (occasionally coagulopathy, bacterial
  infection).
• Caseous Tuberculous.

70
Chronic Pericarditis

• Soldiers plaque (incidental epicardial fibrous
  patch).
• Obliterative pericarditis (incidental post-mortem
  finding).
• Adhesive mediastinopericarditis previous
  suppuration, caseation, cardiac surgery,
  radiation. Heart is bound to surrounding
  structures. Develops marked hypertrophy.
• Constrictive pericarditis Ideopathic or
  following suppuration or caseation. Small quiet
  heart, reduced output, congested veins, pulsus
  paradoxus.

71
Cardiac Tumours

• Secondary (in 5 of tumour autopsies). Primary
  site Lung, breast, melanoma, lymphoma,
  leukaemia. Usually asymptomatic in pericardium
  (pericarditis, effusion) in myocardium
  (arrhythymias, obstruction, congestive failure)
• Primary (rare)
• Myxoma Most in atria, especially left (fossa
  ovalis), sessile or pedunculated (may prolapse
  through and obstruct valve). Effects systemic
  reaction, syncope, cardiac insufficiency, sudden
  death, embolism. Pathogenesis ? hamartoma, ?
  organized thrombus, composed of myxoid tissue
  with smooth muscle cells, macrophages
  (haemosiderin)
• Lipoma Polypoid tumour, may prolapse to obstruct
  or may cause arrhythmias.
• Papillary elastofibroma Organised thrombus with
  papillary projections on valve leaflets ( Lambls
  excresence is a miniature variant frequently
  found at autopsy).
• Rhabdomyoma muscle hamartoma, children, tuberous
  sclerosis, may obstruct.

72
Atheromatous Plaque, Macroscopic

• Fibrous cap (white), deeper portion (grumous,
  yellow).
• 3 - 15 mm diameter, raised, coalesce.
• Scanty to numerous
• Distribution Abdominal aortagt coronary gt
  popliteal gt descending thoracic gtinternal carotid
  gt circle of Willis.
• Spared upper extremities, renal, mesenteric
  (except ostia).

73
Atheromatous Plaque Histology

• Fibrous cap Smooth muscle, WBC, connective
  tissue, collagen, elastic, proteoglycan.
• Core lipid debris, cholesterol, cholesterol
  esters, foam cells ( smooth muscle and
  macrophage), fibrin, plasma proteins, T-cells.
• Periphery neovascularisation, chronic
  inflammation.

74
Effects of Atheromatous Plaque

• Different effects in narrow (coronary) and wide
  (aorta) vessels
• Clinically silent
• Most plaques have no effect.
• Calcification Identify on imaging.
• Complicated plaques
• Fissure
• Ulcerate atheroemboli.
• Thrombose occlude, embolise
• Haemorrhage occlude.
• Consequences
• Stenose Ischaemia, atrophy.
• Occlude (by thrombus or haemorrhage) Infarct.
• Aneurysm pressure effects, leak (rupture)

75
Fatty streak

• Possible precursor of atheroma.
• Spot (1mm), Streak (1x10mm).
• Composition Macrophages filled with lipid (foam
  cells) later smooth muscle cells with lipid
  droplets, extracellular lipid, T-lymphocytes,
  proteoglycans, collagen, elastin.
• Incidence More frequent with high milk/fat diet
  
• 10 first decade, 30 third decade,
• May recede, persist or convert to fibrous plaque
• Distribution Aorta - unlike atheroma, Coronary
  arteries - like atheroma.

76
Intimal Cushion

• White areas of diffuse intimal thickening
  composed of intimal smooth muscle and matrix
  (little collagen, no lipid), gelatinous lesion.
• Degenerate effect of blood pressure and time.
• But occur at ostia (atheroma sites).

77
Monckebergs Calcific Medial Sclerosis

• Calcification of medium or small arteries
• Both sexes, over 50
• Arteries Femoral, radial, ulnar, genital.
• Cause vasotonic factors, adrenaline, nicotine.
• Effect none, visible in imaging

78
Arteriolosclerosis

• Hyaline change in vessel walls.
• Pathogenesis - plasma leakage, smooth muscle
  matrix.
• Associations - hypertension, diabetes, age.
• Benign - hyaline narrowing.
• Hyperplastic - onion skin (fibrinoid necrosis).
• Sites Kidney, gall bladder, intestine,
  periadrenal, pancreatic.

79
Atherosclerosis Risk Factors

• Hyperlipidemia. LDL.
• Hypertension 160/95 Vs 140/90,- Risk X 5.
  Increases Atheroma, IHD, CVD. Risk decreases
  with therapy.
• Cigarettes More AS, more sudden death, Risk
  increased by 70-200. Decreases after cessation.
• Diabetes More AS, MI x 2, Increased CVD, PVD
  risk increased x 8-150.
• Other Physical activity, stress, obesity, oral
  contraceptives, hyperuricemia, high CHO intake,
  male, age, family history, homocystinemia.
• Multiple Factors More than additive.

80
Theories of Atherogenesis

• Virchow - imbibation
• Rokitansky - encrustation

81
Role of lipid in Atherosclerosis

• 1. Found in plaque
• 2. Experimentally raised lipid -gt AS
• 3. Hyperlipidemias -gt AS
• 4. Populations with high lipids -gt high AS rate
• 5. Treat hyperlipidemia - decrease AS.

82
Risk of Atherosclerosis

• High Raised LDL (70 cholesterol), triglyceride
  and VLDL.
• Low Raised HDL.
• Risk increases with increased cholesterol level
  (risk x 5 with cholesterol increase 220 to 265)
• Increased intake cholesterol and triglycerides -
  increases serum cholesterol.
• Omega 3 fatty acids (fish) protective

83
How Hyperlipidemia may damage intima

• More serum LDL, more cellular penetration.
• LDL with proteoglycan - avid uptake.
• LDL modified - lysosomal uptake.
• LDL - directly damages endothelial cell.
• Oxidised lipoproteins Endothelial injury, smooth
  muscle injury, foam cells - scavenger receptor,
  chemotactic.

84
Intimal dysfunction

• Cause Mechanical, Haemodynamic stress, Immune
  complex, Radiation, Chemotherapy.
• Association Hypertension, Stress, Cigarettes.
• Effect Increased intimal permeability, adhesion,
  smooth muscle proliferation, atheroma (if
  hyperlipidemia )

85
Macrophage

• Family Monocyte, histiocyte, macrophage,
  epithelioid cell, giant cell, granuloma
• Monocytes adhere, migrate, phagocytose
• Have scavenger receptor - modified VLDL receptor
  (Lipid internalised, hydrolysed, esterified -gt
  lipid droplet).
• Monocytes produce IL-1, TNF (increased
  adhesion), chemotaxis factors, toxic O2, PDGF,
  TGF beta -gt smooth muscle

86
Smooth muscle proliferation

• Origin From media (or myointima)
• Stimulus PDGF (from platelets, macrophages,
  endothelial and smooth muscle cells), FGF, EGF,
  TGF.
• Inhibit Heparin, TGF-B.
• Result Smooth muscle cells produce
  extracellular matrix and foam cells (atheroma)

87
Arterial Injury

• Permeability increases.
• Adhesion of platelets, monocytes
• Factors released
• Smooth muscle migrates to intima, proliferates
  and produces extracellular matrix, collagen,
  elastin, proteoglycans
• Monocytes - phagocytose
• Lipid deposited

88
Other Theories of Atherogenesis

• Primary smooth muscle proliferation monoclonal
  growth (as a form of leiomyoma)
• Cause Exogenous (hydrocarbon, virus), endogenous
  (cholesterol)
• Experimentally Plaques in Marek chicken virus,
  anthracycline, herpes mRNA in plaque

89
Aneurysms

• Localised abnormal dilation of vessel.
• Types Saccular, fusiform, cylindroid,
  dissection.
• Complications Pressure, thrombus, rupture.
• Aetiology Atherosclerosis, cystic medial
  necrosis, syphilis, trauma (arteriovenous
  aneurysm), PAN, infections, (mycotic), congenital
  (berry).

90
Atherosclerotic Aneurysm

• Males of 50, frequently (50) hypertensive
• Abdominal aorta (between renal artery and aortic
  biforcation). (Thoracic aorta, renal, mesenteric
  arteries)
• Complications
• Rupture (if gt6 cm, 50 rupture in 10 years)
• surgical mortality 50 (unruptured 5)
• Compression - ureter, vertebrae
• Occlusion (thrombus, pressure)
• Embolism
• Abdominal mass

91
Syphilis

• Obliterative endarteritis of vasa vasorum
• Medial destruction with fibrosis (causes tree
  barking or wrinkling of intima and dilation of
  vessel). Aortic valve dilated with rolled
  thickened cusps
• Secondary atherosclerosis usual
• Complications
• Mediastinal encroachment
• Respiratory effects in lung and airway
• Swallowing impairment
• Cough (recurrent laryngeal nerve)
• Pain (involvement of vertebrae and ribs)
• Cardiac effects

92
Dissecting Haematoma (Aneurysm)

• Males x 3 , aged 40 to 60, Females often young,
  pregnant and hypertensive.
• Haematoma between middle and outer 1/3 of vessel
  enters through 4-5 cm transverse intimal tear.
• Type A - Within 10cm of aortic valve.
• Type B - Distal to subclavical artery.
• Haematoma dissects proximal, distal or reenters
  lumen.
• Pain - back, radiates progressively.
• Rupture into pericardial, pleural or
  peritoneal cavity.
• Narrowing of vessels - cerebral or coronary
  insufficiency.

93
Dissecting Haematoma (Aneurysm)

• Cause Hypertension - mechanical stress
• Cystic medial necrosis basophlic mucoid pools
  with fragmented elastic, abnormal collagen,
  elastin, proteoglycan
• Marfan, abnormal collagen cross links.
  Structural effects in retina, lens, joint, aorta,
  abnormal height
• Therapy Surgery, hypotensive therapy.

94
Arteritis

• Arteritis (vasculitis, angiitis).
• Cause Bacterial, irradiation, toxin, trauma,
  collagen disease.
• Immune pathogenesis
• Resemble arthus phenomenon, serum sickness
  (immune complex disorders)
• Found in SLE, Mixed cryoglobulinemia(IgG,M,Comple
  ment)
• Virus Ag/Ab complex, IgGC. HBsAg-antibody
  complex
• Drugs
• Cytotoxic Ab to endothelial cells (SLE) to
  activated endothelial cells (Kawasaki)
• c-ANCA (PAN, Wegeners), p-ANCA (microscopic PAN,
  Churg Strauss)
• T cells granulomas cell mediated immunity

95
Arteritis

• Periarteritis nodosa (PAN)
• Leukocytoclastic vasculitis
• Temporal arteritis
• Wegeners granulomatosis
• Allergic granulomatosis
• Lymphomatoid granulomatosis
• Raynauds
• Buergers
• Takayasus
• Kawasakis

96
Periarteritis Nodosa, Pathology

• Classic type involves medium or small vessels
  (except lung).
• Kidney 85, heart 75, liver 65, GI 50 (also
  pancreas, testes, skeletal muscle, skin).
  
• Involves sharply localised segments of vessels
  especially branching points.
• Stages (may coexist)
• Acute - fibrinoid necrosis (of segments),
  leukocytes, aneurysm formation, thrombus.
• Healing - fibroblastic reaction - nodules,
  macrophages, plasma cells, organised thrombus
• Healed - fibrotic (elastic stains).

97
Periarteritis Nodosa, Clinical

• Ill young adult, (male x 3), fever, malaise,
  weak, raised WCC, PUO, weight loss.
• Renal failure, haematuria, hypertension,
  albuminuria.
• Abdominal pain, melaena.
• Muscle aches and pains, peripheral neuritis.
• Investigate Hepatitis B Ag 30, ANCA,
  Arteriography - nodules (aneurysms)
• Biopsy Kidney, skin.
• Therapy Steroid and cyclophosphamide cure 90.

98
Temporal arteritis

• Granulomatous inflammation of small and medium
  sized cranial arteries
• Morphology giant cell reaction to fragmented
  elastic in vessel wall with polys and
  lymphocytes. Later thrombus formation and intimal
  fibrosis. Segmental involvement biopsy is
  negative in 40.
• Clinical aged, female, high ESR, headache, local
  tenderness, facial pain, visual loss (40). May
  involve aortic arch, GI tract, myocardium, CNS
• Association polymyalgia rheumatica (flu-like
  illness with muscle stiffness.
• Cause ? Cell mediated immunity to arterial
  antigen.
• Responds to steroids

99
Wegeners Granulomatosis

• Acute necrotising granulomatous inflammation of
  upper and lower respiratory tract with focal
  necrotising vasculitis.
• Glomerulonephritis focal necrotising
  glomerulitis, diffuse proliferative or cresentic
  GN.
• Clinical males in 5th decade
• 95 pneumonitis with nodular or cavitating
  infiltrate
• 90 chronic sinusitis
• 75 mucosal ulceration of nasopharnyx
• 80 renal disease
• Also skin rash, muscle pain, articular
  lesions.
• 80 die in one year without treatment. 90
  respond to cyclophosphamide
• Pathogenesis ANCA, Occasionally immune complexes
  found, cell mediated immunity role.

100
Raynaud

• Raynauds Disease.
• Vasospastic disorder of young women, onset
  cold, emotion.
• Involves fingers, hands, nose and feet which
  become white, blue and red.
• Benign Secondary arterial thickening, tropic
  skin changes (atrophy, ulcers).
• Raynauds phenomenon.
• Vasospastic changes in extremities due to
• Atherosclerosis, connective tissue diseases,
  Buergers disease, cryoglobulinemia, myeloma,
  poisoning with ergot or lead, primary pulmonary
  hypertension, systemic sclerosis.

101
Buergers Disease (Migratory Thrombophlebitis)

• Segmental thrombotic acute chronic inflammation
  of intermediate and small vessels (arteries,
  veins and nerves)
• Endothelial sensitivity or toxicity to tobacco,
  catechol amines, collagen II III
  hypersensitivity, HLA 9, B5
• Involves males, strong association with tobacco
  smoking, mainly in Europe, North America
• Pain, vascular insufficiency of lower limbs -
  gangrene, Raynaud phenomenon

102
Varicose Veins

• Dilated tortous veins (legs, portal
  system),female, fat, familial, increase with age
• Aetiology Posture, pregnancy, tumours, poor
  support (superficial veins surrounded by fat)
• Pathology Valves distorted and damaged, vein
  elastica degeneration and calcification and
  fibrosis (phlebosclerosis), luminal thrombus
• Effect Leg congestion, oedema, heavyness, pain,
  stasis dermatitis, tropic changes, ulcer

103
Thrombophlebitis (Deep venous thrombosis)

• Predisposition CCF, cancer, pregnancy,
  bed-rest, immobilisation, post-operative.
• Effects
• Local Deep leg veins (periprostatic, pelvis)
  inflamed - oedema, dilated surrounding veins,
  dusky cyanosis, pain on pressure or dorsiflexion.
• Asymptomatic.
• Pulmonary embolism.
• Diagnose ultrasound, pletysmography, I128,
  angiography
• Prophylaxis Exercise, anticoagulate.

104
Venous thrombosis

• Other sites of venous thrombosis
• Skull sinus thrombosis following meningitis or
  respiratory sinus infection.
• Portal vein thrombosis following peritonitis,
  appendicitis.
• Phlegmasia alba dolens (milk leg) ileofemoral
  thrombophlebitis with lymphatic involvement
  during third trimester.
• Migratory thrombophlebitis Carcinoma of
  pancreas, lung, colon.

105
Lymphatics

• Inflammation Lymphangitis, lymphadenitis
• Obstruction tumour, surgery, radiation,
  inflammation, filiariasis. Results in oedema with
  fibrosis, brawny induration, peau dorange,
  ulceration.
• Leak chylothorax, chylous ascites.
• Lymphoedema praecox Females 10-25 years, lower
  limb. ? cause
• Milroys disease Lymphoedema from birth,
  mendelian, abnormal lymphatics.
• Congenital lymphoedema Similar sporadic, not
  mendelian

106
Vascular Tumours

• Haemangioma, benign. capillary, cavernous,
  granuloma pyogenicum, Lindau von Hipple glomus,
  telangiectasia, spider naevus, naevus flammeus
  (simple birthmark). port-wine stain (disfiguring
  birthmark), Sturge Weber, Osler Weber Rendau
• Malignant.
• Haemangioendothelioma Skin (spleen, liver), low
  grade malignancy.
• Epithelioid soft tissue, lung - 20 metastasise.
• Haemangiopericytoma lower extremites,
  retroperitoneal - 50 metastasise
• Angiosarcoma Skin, soft tissue, breast, liver
  (arsenic, thorotrast, PVC) . High grade
  malignancy
• Kaposis sarcoma immune deficiency, herpes virus