Lecture 51 - Cardiovascular Pathology 3 Flashcards
What is peripheral vascular disease?
Narrowing of blood vessels (usually arteries) that restricts blood flow
mostly int he legs but sometimes in the arms
edimeiology of peripheral vascular disease
smokers - common obese, diabetics, hypertension hypercholesterolaemia Age - increase with age over 40 sex - men more likely and post menopausual women genetic factors developed world
Aetiology of peripheral vascular disease
Agents that can damage the endothelium - lead to atherosclerosis
- smoking
- hypertension
diabetes
hypercholesterolaemic conditions
pathogenesis of peripheral vascular disease
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
clinical features of peripheral vascular disease
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)
6 P’s of acute ischaemia
Pale, pulseless, painful, paralysed, paraesthetic, perishing cold
Clinical consequences of chronic peripheral vascular disease
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
Definition of giant cell arteritis
Chronic granulomatous inflammation of large to small sixed arteries principally int he head
Aetiology of giant cell arteritis
exact cause not known but end stage problems are immune mediated
Epidemiology of giant cell arteritis
most common form of vasculitis
older individuals in US/Europe over 50
Pathogenesis of giant cell arteritis
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
Morphology of giant cell arteritis
Intimal thickening - reduces the lumenal diameter
Med. granulomatous inflammation - elastic lamina fragmentation
Multinucleated giant cells - 75% of adequately biopsied
Key clinical features of giant cell arteritis
Rare - less than age 50, vague symptoms eg. fatigue, weight loss,
Facial pain or headache
- Superficial temporal artery (painful to palpation)
- Jaw claudication
Diagnosis of giant cell arteritis
Biopsy and histologic
- segmental disease
- hence 2-3 cm length of artery
Treatment of giant cell arteritis
Corticosteroids is generally effective
Anti TNF therapy in refractory cases
What is endocarditis
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)
Epidemiology of endocarditis
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
Aetiology of endocarditis
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%)
How does an infection get to the heart
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
Pathogenesis of infective endocarditis
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
Clinical features of endocarditis
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
complications of infective endocarditis
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
Infective endocarditis symptoms
F - FEVER
R - ROTH SPOTS
O - OSLER’S NODES
M - MURMURS
J - JANEWAY LESIONS
A - ANAEMIA
N - NAIL (SPLINTER) HAEMORRHAGE
E - EMBOLI (SEPTIC)
Rheumatic fever - definition
Acute, immunologically mediated, multi-system inflammatory disease
following group A - streptococcal pharyngitis
Epidemiology of rheumatic fever
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
Rheumatic fever aetiology
Group A Streptococcal pharyngitis
Pathological features of rheumatic fever
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
Pathogenesis of rheumatic fever
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
Clinical features of rheumatic fever
Left atrium dilates - mural thrombi form - embolise
Right ventricular hypertrophy
Pericarditis
Inflammation of the pericardial sac
Epidemiology of Pericarditis
depends on cause
Aetiology
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
Pathogenesis of Pericarditis
Acute Pericarditis (inflamed)
- Serous
- Serofibrinous/ fibrinous
- Purulent /suppurative
- Haemorrhagic
- Caseous
Chronic pericarditis (stuck down)
- Adhesive
- Adhesive mediastinopericarditis
- Constrictive pericarditis
Serous pericarditis
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
Serofibrinous pericarditis
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
Purulent pericarditis
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!
Haemorrhagic pericarditis
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
chronic pericarditis
Adhesive pericarditis / Constrictive pericarditis
Adhesive pericarditis / Constrictive pericarditis
Fibrosis / stringy adhesions obliterates pericardial cavity
Heart can become encased in fibrous scar – limits cardiac function
Treated by surgery to remove ‘shell’ around heart
Key Clinical features of Pericarditis
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
Cardiomyopathy
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)
Epidemiology of cardiomyopathy
depends on subtypes
Aetiology of cardiomyopathy
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)
Pathogenesis of cardiomyopathy
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)
Dilated cardiomyopathy
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….
Epidemiology and prognosis for cardiomyopathy
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)
Hypertrophic cardiomyopathy
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
Hypertrophic cardiomyopathy - clinical features
↓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.
Complications/treatment of hypertrophic cardiomyopathy
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
Restrictive cardiomyopathy
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
Arrythmogenic right ventricular cardiomyopathy
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
myocarditis
inflammation of myocardium
epidemiology of myocarditis
Varies depends on cause
Aetiology of myocarditis
INFECTIONS viruses bacteria fungi protozoa helminths chlamydiae rickettsiae
IMMUNE MEDIATED post - viral post - streptococcal SLE Drugs transplant rejection
OTHERS
Sarcoidosis
Giant cell myocarditis
Pathogenesis of myocarditis
Infection or inflammatory trigger
cytokines, cytotoxic damage, damage myocytes
myocytes +/or endothelium malfunction
electrical problems / mechanical problems / clotting problems
Clinical features of myocarditis
Broad spectrum of changes Asymptomatic Chest pain CHF Arrhythmias Sudden death
