Lecture 51 - Cardiovascular Pathology 3

Question 1

What is peripheral vascular disease?

Answer 1

Narrowing of blood vessels (usually arteries) that restricts blood flow

mostly int he legs but sometimes in the arms

Question 2

edimeiology of peripheral vascular disease

Answer 2

smokers - common
obese, diabetics,
hypertension
hypercholesterolaemia
Age - increase with age over 40
sex - men more likely and post menopausual women
genetic factors
developed world

Question 3

Aetiology of peripheral vascular disease

Answer 3

Agents that can damage the endothelium - lead to atherosclerosis

• smoking
• hypertension
  diabetes
  hypercholesterolaemic conditions

Question 4

pathogenesis of peripheral vascular disease

Answer 4

Causative agents damage the endothelium - trigger cellular events - lead to eccentric wall thickening by atheroma +/- thrombosis

+/- embolism - narrow lumen - reduced blood flow
- narrows artery - ischaemia - cell damage

all symptoms and consequences of PVD are related to restricted blood flow

Question 5

clinical features of peripheral vascular disease

Answer 5

progressive disease leading to increasing levels of tissue hypoxia

narrowed lumen - decreased perfusion (pain, cold, pale peripheries, loss of function, eventually can be cell death gangrene)

• ruptured plaque - sudden increase in narrowing or emboli from plaque or thrombus (actute onset peripheral pallor and pain and loss of function - more gangrene)

Question 6

6 P’s of acute ischaemia

Answer 6

Pale, pulseless, painful, paralysed, paraesthetic, perishing cold

Question 7

Clinical consequences of chronic peripheral vascular disease

Answer 7

Symptoms vary depending on severity
Critical limb ischaemia

Asymptomatic - found during a physical exam

intermittent claudication - symptomatic = complaint of pain upon exertion

Critical limb ischaemia - Rest pain, tissue loss

Question 8

Definition of giant cell arteritis

Answer 8

Chronic granulomatous inflammation of large to small sixed arteries principally int he head

Question 9

Aetiology of giant cell arteritis

Answer 9

exact cause not known but end stage problems are immune mediated

Question 10

Epidemiology of giant cell arteritis

Answer 10

most common form of vasculitis

older individuals in US/Europe over 50

Question 11

Pathogenesis of giant cell arteritis

Answer 11

Chronic granulomatous inflammation - narrows artery - ischaemia - cell damage

esp in head - temportal arteries - aka temporal arteritis
also vertebral and ophthalmic arteries
ophthalmic arterial involvement
-permanent blindness
- giant-cell arteritis is a medical emergency requiring prompt recognition and treatment - vital

• also occurs in other vessels
• eg aorta - giant-cell aortitis

Question 12

Morphology of giant cell arteritis

Answer 12

Intimal thickening - reduces the lumenal diameter

Med. granulomatous inflammation - elastic lamina fragmentation

Multinucleated giant cells - 75% of adequately biopsied

Question 13

Key clinical features of giant cell arteritis

Answer 13

Rare - less than age 50, vague symptoms eg. fatigue, weight loss,

Facial pain or headache

• Superficial temporal artery (painful to palpation)
• Jaw claudication

Question 14

Diagnosis of giant cell arteritis

Answer 14

Biopsy and histologic

• segmental disease
• hence 2-3 cm length of artery

Question 15

Treatment of giant cell arteritis

Answer 15

Corticosteroids is generally effective

Anti TNF therapy in refractory cases

Question 16

What is endocarditis

Answer 16

Inflammation of the endocardium - lining of the heart inflamed, mainly involves the valves

Typical lesion = Vegetation on valves

2 main forms

Infective endocarditis
- Clinically important

Non-infective endocarditis - not covered

• Nonbacterial thrombotic endocarditis (NBTE)
• Endocarditis of SLE (Libman-Sacks Disease)

Question 17

Epidemiology of endocarditis

Answer 17

Can occur in normal heart - with highly virulent organisms

more common in background of

Structural abnormality of valves or myocardium
-With organisms of lower virulence (>Sub-acute infective endocarditis = not so nasty

Including:
- RHD was major cause of

more common causes now

• MV Prolapse
• Valvular stenosis (calcification etc)
• Artificial (prosthetic) valves
• Unrepaired and repaired congenital defects
• Bicuspid AV

Question 18

Aetiology of endocarditis

Answer 18

Mouth - dental disease or procedures - alpha haemolytic viridans streptococci. 1/3 - 1/2 of cases - more in underdeveloped countries

gut and perineum - enterococci eg. E faecalis, can cause urinary sepsis

Bowel malignancy - strep. bovis (rare)

Prolonged indwelling vascular catheter - staph aureus and candida

Native and prosthetic valve endocarditis
Early - poor prognosis - occurring within 60 days of valve surgery and acquired in the theatre or soon in the theatre or soon thereafter perhaps n the intensive care unit

Late - occurring more than 60 days after valve surgery and presumed to have been acquired in the community

• Strep viridans (50-70%)
• Staph aureus (25%)

Question 19

How does an infection get to the heart

Answer 19

Any route of bacteria into blood stream eg. dental abnormalities, IVDU, wounds, bowel cancer

• Streptococcus viridans from the mouth
• Endocarditis in native but damaged/ abnormal valves
• 50-60% of cases

S. aureus from the skin
- 10-20% of cases overall esp. IVDU

Coagulase-negative staphylococci (e.g. epidermidis)
-Commonly infect prosthetic heart valves

Question 20

Pathogenesis of infective endocarditis

Answer 20

Clinically serious infection

-colonization/invasion of heart valves or heart chamber endocardium by a microbe

Vegetations made of thrombus and organisms

• Destroy underlying heart or vascular tissues (eg. aorta)
• aneurysmal sacs
• abscesses local and distant (emboli)
• septic infarcts or mycotic aneurysms

Most cases bacterial
- Fungi/other classes can also cause

Question 21

Clinical features of endocarditis

Answer 21

Fever

• most consistent sign
• rapidly developing fever, chills, weakness
• can be slight or absent, particularly in the elderly

Non-specific symptoms

• May be only presentation
• Loss of weight/flu-like syndrome

Murmurs

• 90% of patients with left-sided IE (infective endocarditis)
• New valvular defect or represent a pre-existing abnormality

Question 22

complications of infective endocarditis

Answer 22

immunologically mediated conditions - eg. glomerulonephritis

Clinical manifestations (micro-thromboemboli)
-splinter/sublngual haemorrhages
- Janeway lesions
Erythematous or haemorrhagic non-tended lesions on the palms or soles
-Osler’s nodes
subcutaneous nodules in the pulp of the digits
-Roth spots
Retinal haemorrhages in the eyes

Question 23

Infective endocarditis symptoms

Answer 23

F - FEVER
R - ROTH SPOTS
O - OSLER’S NODES
M - MURMURS

J - JANEWAY LESIONS
A - ANAEMIA
N - NAIL (SPLINTER) HAEMORRHAGE
E - EMBOLI (SEPTIC)

Question 24

Rheumatic fever - definition

Answer 24

Acute, immunologically mediated, multi-system inflammatory disease

following group A - streptococcal pharyngitis

Question 25

Epidemiology of rheumatic fever

Answer 25

Rare in developed world because of improved diagnosis/treatment - 15 million in developing countries (Africa, Middle and Far East in particular)/ poor Western populations Age - typically children 5-15

Question 26

Rheumatic fever aetiology

Answer 26

Group A Streptococcal pharyngitis

Question 27

Pathological features of rheumatic fever

Answer 27

veruccae = vegetations Mitral valve changes are classical - Virtually only cause of mitral stenosis - Leaflet thickening - Virtually always involved in chronic disease MV only in most cases Aortic valve in 25% of cases Tricuspid valve /pulmonary valves - uncommon - Fibrous bridging of valvular commissures and calcification - FISH MOUTH or buttonhole stenoses

Question 28

Pathogenesis of rheumatic fever

Answer 28

Due to hypersensitivity reactions - Combined antibody and T- cell mediated response to self antigens in the heart Group A strep (pharyngitis) - antibodies and T cells - which make cytokines that activate macrophages (e.g. Aschoff bodies) - Cross react with self protein in the heart

Question 29

Clinical features of rheumatic fever

Answer 29

Left atrium dilates - mural thrombi form - embolise | Right ventricular hypertrophy

Question 30

Pericarditis

Answer 30

Inflammation of the pericardial sac

Question 31

Epidemiology of Pericarditis

Answer 31

depends on cause

Question 32

Aetiology

Answer 32

Infections - viruses (Coxsackie B), bacteria, TB, fungi, parasites Autoimmune - Rheumatic fever, SLE, Scleroderma, post-cardiotomy - Late post - MI = Dressler's drug hypersensitivity Miscellaneous - Post - MI (early), uraemia, cardiac surgery, neoplasia, - Trauma, radiation

Question 33

Pathogenesis of Pericarditis

Answer 33

Acute Pericarditis (inflamed) - Serous - Serofibrinous/ fibrinous - Purulent /suppurative - Haemorrhagic - Caseous Chronic pericarditis (stuck down) - Adhesive - Adhesive mediastinopericarditis - Constrictive pericarditis

Question 34

Serous pericarditis

Answer 34

Inflammation causes clear 'serous' fluid accumulation Caused by non-infectious aetiologies (generally) - inflammation in adjacent structures can cause pericardial reaction - Rarely by viral pericarditis (Coxsackie B / echovirus) Autoimmune - Rheumatic fever, SLE, scleroderma Other - Uraemia, neoplasia, radiation

Question 35

Serofibrinous pericarditis

Answer 35

Serous fluid and / or fibrinous exudate in pericardial sac This is the most common form of pericarditis! Common causes - Acute MI, Dressler’s syndrome - Uraemia, radiation, rheumatic fever, SLE, trauma, surgery Features of fibrinous pericarditis (without fluid) - Dry, granular, roughened surface - More intense inflammatory response -> sero-fibrinous

Question 36

Purulent pericarditis

Answer 36

infections Features of purulent / suppurative pericarditis Red, granular, exudate i.e. pus (can be up to 500mls!) Inflammation can extend causing mediastino-pericarditis Outcome – complete resolution is rare Organisation by scarring  restrictive pericarditis – serious!

Question 37

Haemorrhagic pericarditis

Answer 37

Blood mixed with serous (watery) or suppurative (pus) effusion Common causes Neoplasia (malignant cells in effusion) Infections (inc TB) Following cardiac surgery  cardiac tamponade Caseous (cheesy) pericarditis TB or fungal

Question 38

chronic pericarditis

Answer 38

Adhesive pericarditis / Constrictive pericarditis

Question 39

Adhesive pericarditis / Constrictive pericarditis

Answer 39

Fibrosis / stringy adhesions obliterates pericardial cavity Heart can become encased in fibrous scar – limits cardiac function Treated by surgery to remove ‘shell’ around heart

Question 40

Key Clinical features of Pericarditis

Answer 40

``` Sharp central chest pain…characteristics Exacerbated by : movement, respiration, laying flat Relieved : sitting forwards Radiating : shoulders / neck Differentials : angina, pleurisy ``` Pericardial friction rub Fever, leucocytosis, lymphocytosis, pericardial effusion Complications – pericardial effusion / cardiac tamponade

Question 41

Cardiomyopathy

Answer 41

Literally means “heart muscle disease” and strictly speaking is of uncertain cause (but see later…) 4 main types -Dilated -Hypertrophic -Restrictive -Arrythmogenic right ventricular cardiomyopathy (dysplasia)

Question 42

Epidemiology of cardiomyopathy

Answer 42

depends on subtypes

Question 43

Aetiology of cardiomyopathy

Answer 43

Unknown… (tho’ there is a genetic component in many really) (NB need exclusion of commoner causes of myocardial failure - hypertension, IHD, valvular and congenital HD)

Question 44

Pathogenesis of cardiomyopathy

Answer 44

Main ways the pathological abnormality causes signs and symptoms: Heart Failure (abnormal muscle cannot cope with workload) Emboli (It’s that Virchow’s Triad again…) Arrhythmias (Disruption of electrical conduction pathways)

Question 45

Dilated cardiomyopathy

Answer 45

Progressive dilation  contractile (systolic) dysfunction Heart enlarged, heavy, flabby (dilation of chambers) Myocyte hypertrophy with fibrosis Associations Genetic (20 – 50% cases) Autosomal dominant (mainly) Cytoskeletal proteins gene mutation Alcohol (10-20%) and other toxins E.g. chemotherapy Others SLE, scleroderma, thiamine def., acromegaly, thyrotoxicosis, diabetes….

Question 46

Epidemiology and prognosis for cardiomyopathy

Answer 46

Any age but commonly 20 – 50 Slow progressive signs / symptoms of CCF SoB, fatigue, and poor exertional capacity 5 year survival = ~ 25% (like the ejection fraction…) Death due to CCF, arrhythmia / embolism (intra-cardiac thrombus) Treatment Cardiac transplantation Long-term ventricular assist (can induce regression)

Question 47

Hypertrophic cardiomyopathy

Answer 47

Defined by myocardial hypertrophy Thick-walled, heavy, poorly compliant left ventricular myocardium Diastolic dysfunction with preserved systolic function Intermittent ventricular outflow obstruction (1/3 cases) ie Stiff ventricle that doesn’t fill properly If LVH, no Hypertension, no Valve Disease - think of this 100% genetic (so much for unknown cause…) Mutations sarcomeric proteins, Can be sporadic

Question 48

Hypertrophic cardiomyopathy - clinical features

Answer 48

↓Stroke volume Impaired diastolic filling - reduced chamber size / compliance of hypertrophied left ventricle Obstruction to the left ventricular outflow 25% of patients Exertional dyspnoea due to above Systolic ejection murmur Ventricular outflow obstruction Anterior mitral leaflet moves toward the ventricular septum during systole.

Question 49

Complications/treatment of hypertrophic cardiomyopathy

Answer 49

Complications Atrial fibrillation Mural thrombus formation  embolization / stroke Cardiac failure Ventricular arrhythmias Sudden death, especially in some affected families Most common causes of sudden death in athletes Treatment Decrease heart rate and contractility - β-adrenergic blockers. Reduction of the mass of the septum, which relieves the outflow tract obstruction

Question 50

Restrictive cardiomyopathy

Answer 50

Rare Primary disease in ventricular compliance - Impaired ventricular filling during diastole Idiopathic or secondary (infiltration) -Fibrosis, amyloidosis, sarcoidosis, metastatic tumours or deposition of metabolites (inborn errors of metabolism) Morphology -Ventricles normal size / slightly enlarged chambers normal - Myocardium is firm and noncompliant

Question 51

Arrythmogenic right ventricular cardiomyopathy

Answer 51

``` AKA arrhythmogenic R.V. dysplasia Genetic disease (A.D.), ~1 in 5000 RV dilation / myocardial thinning Fibrofatty replacement of RV Disorder of cell-cell desmosomes Exercise -> cells detach and die Silent, syncope, chest pain, palpitations Sudden cardiac death – young / exercise ```

Question 52

myocarditis

Answer 52

inflammation of myocardium

Question 53

epidemiology of myocarditis

Answer 53

Varies depends on cause

Question 54

Aetiology of myocarditis

Answer 54

``` INFECTIONS viruses bacteria fungi protozoa helminths chlamydiae rickettsiae ``` ``` IMMUNE MEDIATED post - viral post - streptococcal SLE Drugs transplant rejection ``` OTHERS Sarcoidosis Giant cell myocarditis

Question 55

Pathogenesis of myocarditis

Answer 55

Infection or inflammatory trigger  cytokines, cytotoxic damage, damage myocytes  myocytes +/or endothelium malfunction  electrical problems / mechanical problems / clotting problems

Question 56

Clinical features of myocarditis

Answer 56

``` Broad spectrum of changes Asymptomatic Chest pain CHF Arrhythmias Sudden death ```