Cardio-Vascular Pathology Flashcards
Define heart failure
Inability of the heart to pump blood at a rate commensurate with the requirements of the metabolising tissues
How does heart failure develop
Slowly
- cardiac hypertrophy
actue
- MI
- acute valve dysfunction
How common is heart failure
5 million in US
- commonest discharge diagnosis in under 65
- under 1 million hospitalised
What are the two types of heart failure
- Systolic dysfunction
- Diastolic dysfunction
Name the causes of systolic dysfunction
- Ischaemic heart disease
- pressure or volume overload such as systemic hypertension or aortic stenosis (AS)
- Cardiomyopathy
Name the causes of diastolic dysfunction
- Inability to reflex/fill
- amyloid deposition
- myocardial fibrosis
- constrictive pericarditis - after radiotherapy particularly for breast, TB, connective tissue disorders
How does amyloid deposition interfere with tissues function
- a collection of protein that are undigestible by the proteases therefore the protein when deposited in tissues interferes with the tissues function
What are the two consequences of heart failure
Forward
Backward
describe the forward and backward problem (consequence of heart failure)
Forward
- deliver the oxygen to the organs.
- The heart is not pumping out enough blood to satisfy the needs of the cells of the body. Thus, excess fluid retention and edema increase
backward
- hypoxic blood in the venous system
- One of the ventricles fails to pump out all of its blood that comes into it. Thus, the ventricular filling pressure and systemic or pulmonary edema increase.
Name mechanisms that are used to cope with heart failure
- frank-starling
- hypertrophy +/- chamber dilation
- activation of neurohormonal systems such as noradrenaline, RAAS and atrial natriuretic peptide
- may eventually be exceeded
What is the frank starling law
- this is the idea that increase in stretching of the heart causes an increase in contraction
- relation to EDV - as EDV increases this causes the heart muscle to stretch and increase in contraction to pump the EDV out
What are the consequences of heart failure
- Heart size/weight increase
- hypertrophy
- pressure overload - concentric hypertrophy
- volume overload - cavitary dilation maybe without thickening
- hypertrophy - can cause capillary decrease - increase in fibrous tissue - increase metabolic needs - vicious circle that leads to failure
Anything that does cause hypertrophy in the left ventricle is associated with…
Sudden death
Why do people who have left sided heart failure present the way they do
Main features are due to decreased peripheral pressure and damming of blood in the pulmonary circulation
What is the presentation of someone with left sided heart failure
- Lung congestion
- oedema
- accumulation of haemosiderin laden macros - leads to dyspneoa due to fluid build up on lungs, orthopnoea - fluid getting worse when you lie down, PND
- heart depends on cause - IDH, HT, Valves
- Brain and kidneys if severe suffer hypoxia (hypoxia - peripheral blood becomes hypoxic)
Describe what causes the symptoms of right sided heart failure
- Usually secondary to LVF
- primary association with severe pulmonary hypertension
What are the symptoms of right sided heart failure
Liver
- pure liver congested - nutmeg
- centrilobular necrossi and firbosis
- portal vein pressure increase - splenomegaly, ascities, kidneys and brain hypoxia, peripheral oedema
- biventricular - plus LVF
What is hypertension defined as
- systolic greater than 140mmHg
- diastolic greater than 90mmHg
What is hypertension as risk factor for
- IDH
- Cerebrovascular disease
- aortic dissection
- cardiac failure
- renal failure
Name the types of hypertension
- Primary/essential (95%)
- secondary
- benign or malignant/accelerated (5%)(has severe end organ damage)
Name the causes of secondary hypertension
Renal
- Chronic renal disease
- glomerulonephritis
- renal artery stenosis
Neurological
- stress including surgery
- psychogenic
- raised intracranial pressure
Cardiovascular
- coarctation of the aorta
- systemic vasculitis
- increased intravascular volume
Endocrine
- cushings
- conns
- exogenous hormones
- pheochromocytoma
- acromegaly
- thyroid disease
- pregnancy
How do you measure blood pressure
Cardiac output x peripheral resistance
What influences cardiac output
Blood volume
- sodium
- mineralocorticoids
cardiac factors
- heart rate
- contractility
What influences peripheral resistance
Constrictors
- angiotensin II
- catecholamines
- thromboxane
- leukotrienes
- endotheliin
- alpha adrenergic
Dilators
- prostaglandins
- NO
- Beta adrenergic
local factors
- autoregulation
- ionic (pH, hypoxia)
What do you see in the heart when someone has hypertension
- Left ventricular hypertrophy
What do you see in the vessels in someone who has hypertension
- atheroma
- aortic dissection,
- cerebrovascular haemorrhages,
- degenerative changes such as fibrointimal thickening
What do you see in the small vessels in someone who has hypertension
- hyaline arteriolosclerosis esp kidneys,
- hyperplastic arteriolosclerosis (onion-skinning)
- fibrinoid necrosis in accelerated
What is cor pulmonale
Heart disease as a consequence to lung disease
What is pulmonary hypertension
High blood pressure in the pulmonary circulation
What can cause pulmonary hypertension
- diseases of the lung parenchyma such as COPD, cystic fibrosis, diffuse interstitial fibrosis
- diseases of the pulmonary vessels such as recurrent, PEs, primary PH, severe vasculiits
- Disorders affecting chest movement such as kyphoscoliosis, neuromuscular disease
- disorders causing arterial constriction such as hypoxaemia, chronic altitude sickness
What are the two types of cor pulmonale
Acute - massive PE can cause this
Chronic - most of the time
What changes do you see with cor pulmonale in the heart
- RV hypertrophy
- RA hypertrophy
- dilatation in both chambers
- due to the dilation the tricuspid valve ring may become expansive and this can lead to tricuspid regurgitation
- see the clinical features for RVF plus the primary disease
What is right ventricular hypertrophy defined as
Thickened right ventricle above 0.5cm
What is vasculitis
- inflammation of the vessel walls
- can be infective or non infectious
What can cause non infectious vasculitis
- immune complex
- ANCA- mediated
- direct antibody mediated
- cell mediated
- paraneoplastic or idiopathic
What is classification of vasculitis based on
- pathogenesis
- vessel size
Name some examples of
- Large vessel vasculitis
- medium vessel vasculitis
- ANCA - associated small vessel vasculitis
Large vessel vasculitis
- takayasu artertitis
- giant cell arteritis
Medium vessel vasculitis
- Polyarteritis Nodosa
- Kawasaki disease
ANCA - associated small vessel vasculitis
- Microscopic polyangitis
- granulomatosis with polyangitis
- eosinophillic granulomatosis with polyangitis
How does vasculitis show
- All show vascular injury with mural necrosis and haemorrhage
- localised, organ restricted or systemic
- some are granulomatous
- secondary ischaemia of down-stream tissue
- may cause infarction
What are granulomas
localised collections of epithelial macrophages
What is polyarteritis nodosa
- Systemic vasculitis
- small/medium sized arteries (not veins or smaller arteries)
- often spares the lungs
Describe what you see in polyarteritis nodosa
- Segmental necrotising inflammation of arteries especially renal, cardiac and GI tract
- branching sites particularly
What does polyarteritis nodosa lead to
- Aneurysms, infracts and haemorrhage
- microscopically transmural inflammation and fibrinoid necrosis
- possible thrombosis of vessel
- fibrosis later become nodular
- lesions of different ages
who does polyarteritis nodosa tend to effect
- Young adults
- more common in men than in women
How does polyarteritis nodosa present
Episodic
acute, subacute, or chronic
- fever
- malaise
- weight loss
- hypertension
- abdominal pain
- malaena
- muscular pains
- renal involvement
- peripheral neuritis
What is the treatment of polyarteritis nodosa
- steroids
- cyclophosphamide
What antigen presents along with polyarteritis nodosa
30% hep B antigen positive
What are ANCA related vasculitis
- 85% ANCA antibodies (60-95%)
- group of vasculitis that can be systemic, renal limited or other
How does ANCA vasculitis present
- flu like illness
- fever
- arthralgia
- myalgia
- purpura
- peripheral neuropathy
- gastro-intestinal involvement
What can provoke ANCA vasculitis
- propylthiouracil
- penicillamine
- hydralazine
What are the two staining patters for somone with ANCA related vasculitis and what antibody do they stain
- Cytoplasmic by IMF - c-ANCA is usually proteinase 3 (PR3)
- perinuclear by IMF - usually myeloperoxidase (MPO)
- can have ANCA circulating in patients who do not have vasculitis
What is granulomatosis with polyangitis
- effects upper and lower respriatory tract
- particular the eyes and ear
- see necrotising grnauloma
- vasculitis
- target is proteinase 3 (PR3) - you see c-ANCA usually
How do you treat ANCA
- aggressive immunosupression with cyclophosphamide (IV, V oral) and steroids if patient an tolerate
what are the prognosis for ANCA with and without treatment
- Untreated 80% 1 year mortality
- Treated 75% 5 year survival (kidney involvement and patient)
What is cardiomyopathy
cardiac disease that arises from a primary intrinsic myocardial abnormality
what are the causes of cardiomyopathy
- Idiopathy
- Secondary to known cause
- Primary
Name the 4 types of cardiomyopathy
• dilated
• hypertrophic
• restrictive
- arrhythomogenic right ventricular cardiomyopathy
Describe what dilation cardiomyopathy look like
4 chamber dilation
- bigger heart
Describe what hypertrophic cardiomyopathy looks like
- septum thickening
Describe what restrictive cardiomyopathy look like
- heart looks normal and only able to diagnose it on functional analysis, ECG, biopsy or autopsy
describe what happens in dilated cardiomyopathy
- Progressive cardiac dilatation and contractile dysfunction
- valves/arteries not significantly abnormal
- may be thrombi
- micro - myocardial hypertrophy/fibrosis
What is the cause of dilated cardiomyopathy
- Idiopathic
- Genetic (~30%)
- Post myocarditis
- Alcohol or other toxicity eg doxorubicin
- Pregnancy associated
- Haemochromatosis
- Sarcoidosis
What age does dilated cardiomyopathy occur in
- any age but especially 20-50
what are the signs of dilated cardiomyopathy
- progressive CCF
- signs of LVF+RVF
- death from failure or sudden death (arrhythmia)
What is the treatment of dilated cardiomyopathy
Transplantation
What happens in hypertrophic cardiomyopathy
- Heart muscle is abnormal
- fills poorly in diastole
- often an outflow obstruction due to thickened septum
- little or no dilatation
- classically disproportionate thickening of septal myocardium epsically subarotic
- micro hypertrophy, disarray and fibrosis
What is the most common genetic problem associated with hypertrophic cardiomyopathy
- Mutation of muscle protein esp beta-myosin heavy chain
- most familial
- many different mutations found
- leads to poor compliance and reduced LV chamber size +/- outflow obstruction
- clinically heterogeneous, may need surgery
What is the most common genetic problem associated with hypertrophic cardiomyopathy
Beta myosin heavy chain
Describe restrictive cardiomyopathy
- Primary disease in ventricular compliance
- idiopathic
- firm ventricles with normal dilated atria
- microscopy may reveal cause
What can cause secondary restrictive cardiomyopathy
- irradiation fibrosis
- amyloid
- sarcoid
- tumour metastases
What is myocarditis
- inflammation causing myocardial injury and not a response to it
What infections can cause myocarditis
- viruses such as Coxackieviruses, enteroviruses, other viruses including HIV; chlamydia, rickettsiae, bacteria, fungi, protozoa, Helminths
What immunological reactions can cause myocarditis
– post-viral, SLE, drug reactions, transplant rej
What can also cause myocarditis
sarcoidosis, giant cell myocarditis
what can cause direct damage to the myocarditis
May be direct damage or T cell mediated injury to antigens on myocyte surface
• Inflammation and myocyte necrosis
How do the patients present in myocarditis
- fatigue
- fever
- chest discomfort
- heart failure
- arrhythmias
- sudden death
myocarditis and
acute infract can be confused due to similar symptoms
What does myocarditis lead onto
- dilated cardiomyopathy
