Cardiovascular Pathology Flashcards
arteriosclerosis
process occurs with aging, deposition of amyloid, hyperplasia of smooth muscles, effects small BVs more
atherosclerosis
Can occur at any age (mainly elderly)
deposition of cholesterol on vessels - mainly larger vessels
- plaque build up
what causes nearly half of all deaths in the Western World?
artherosclerosis
which types of factors cause arteriosclerosis?
its is multifactorial so both modifiable (lifestyle) and non-modifiable factors can cause atherosclerosis
modifiable factors
lifestyle (smoking, diet, obesity etc)
non-modifiable factors
genes (DNA), age, gender
what is the most important risk factor in atherosclerosis?
Hyperlipidaemia
High cholesterol
what are the 2 processes in atherosclerosis?
Achronic inflammatory process followed by healing response
Chronic inflammatory process
- Initiates an inflammatory reaction as cholesterol deposited in not correct place
Followed by healing process - but doesn’t heal
Formation of an atheroma
what is an atheroma?
a.k.a. a plaque
forms as a result of the artherosclerosis process
- Has a gruel like texture
define vascular pathology
either stenosis/obstruction or to weakening of the walls leading to dilatation/rupture
define stenosis
narrowing of blood vessel
define aneurism
weakening of vessel wall leading to rupture
non-modifiable factors of atherosclerosis
- age
- gender
- genes
age impact on athersclerosis
older are more likely to get
gender impact on athersclerosis
Males higher than females (before menopause low risk of many cardiovascular disease as oestrogen binds to BV keeping them open) age determines risk factor
genes impact on atherosclerosis
Familial hypercholesterolaemia. (Mutation of LDL receptor gene.)
- LDL receptor gene is an Autosomal dominant condition
Liver cells take up circulating LDL of bad cholesterol
Heterozygote - one mutant and one normal gene (50% increase in level of circulating LDL)
- Higher risk of cardiovascular disease
Very high cholesterol level if both mutated - need statins from early age
- Some families have this trait - more risk
LDL receptors present in many cell types including smooth muscle cells, fibroblasts and adrenocortical cells.
2 endothelial cell states
- basal state (normal)
- activated state (pathology)
features of basal (normal) endothelial cell
- Smooth
- non-adhesive and non-thrombogenic surface
features of activated (pathology) endothelial cell
- Initiates lots of different changes cause of change in BV walls
- increased expression of procoagulants, adhesion molecules and proinflammatory factors
- altered expression of chemokines, cytokines and growth factors
when will we have basal (normal) endothelial cells?
- Lines our blood vessels
- when Normal BP in normal range - normal state (no trauma or insult)
- laminar flow
- growth factors (e.g. VEGF)
when will we have activated (pathology) endothelial cells?
- turbulent flow
- hypertension
- cytokines
- complement
- bacterial products
- lipid products
- advanced glycation end-products
- hypoxia, acidosis
- viruses
- cigarette smoke
2 basic stages of atheroma formation
- chronic inflammation stage
- healing response phase
chronic inflammation stage of atheroma formation
Chronic inflammatory response to lipoproteins
- Something causing damage to endothelial cells - changing receptors - changing permeability
- High levels of cholesterol
Endothelial cells change surface cell receptors and become more permeable to lipids.
- Lipids move into tunica intima (first BV layer)
Change cell adhesion molecules for monocytes so attach
to endothelium and move into blood vessel walls.
- Macrophages are the first cell there
- Easier for inflammatory cells to move from blood to vessel walls
Monocytes include macrophages and T-cells.
Foam cells, lipid deposits from dead cells.
healing response phase of atheroma formation
Proliferation of smooth muscle cells
Fibrous tissue formation
- More division of fibroblasts and inflammatory cells - viscous cycle (brought in by macrophage and fibroblasts
Growth factors such as PDGF, FGF, TGF-α, are produced.
A fibro fatty plaque is formed with a central mass of lipid and necrotic tissue.
Neovascularization may be seen at the periphery of the plaque.
Haemorrhage can occur into the plaque.
Calcification of the lipid and necrotic tissue may sometimes occur
- Increase in size of atheroma – fatal consequence
5 steps of the atheroma formation process
- Chronic endothelial cell injury may be genetic mutation, inherited, hypertension etc.
- Permeability increases. lipid is deposited in the intimal layers.
- Macrophages move in.
- Foam cells
- Fatty streaks
- May regress - Smooth muscle proliferation
- Macrophages produce IL-1 which activates T-cells.
- More cytokines, chemokines, ROS activate more inflammatory cells
- PLGF, FGF, TGF-α, - Fibrous tissue formation, over the lipid and a fibro fatty atheroma is formed (plaque)
- Dystrophic calcification may occur at late stages
what happens to the lumen of the blood vessel as a consequence of atheroma formation/
shrinks (as increased tunica media)
so not enough room for blood transportation
what is the effect of atherosclerosis?
decreased blood supply to tissue/organ (ischemia)
thrombosis on top of atheroma and embolisms break off
the effect of atherosclerosis depends on what?
- size of BV
- extent of obstruction
- organ effected
what does complete occlusion of the blood vessel lead to?
infarction (cell death)
what does partial occlusion of the blood vessel lead to?
Less O2, nutrient to cell – ischemia
what is a dental condition that could be caused as a result of atherosclerosis?
death of the pulp is blockage of vessel supplying the pulp
(external carotid –> maxillary –> anterior superior alveolar artery, the middle superior alveolar artery and the posterior superior alveolar artery.)
peripheral vascular disease
Effects BV all over body
- In particular legs
effects of peripheral vascular disease
- ischemia
- claudication
- gangrene
- coagulation necrosis and infection
claudication
pain of cramps released by rest
aneurysms
abnormal dilation, caused by a localised, abnormal, weak spot on a blood vessel wall
- Can occur in blood vessel or in the cardiac wall as well as other places in the body.
what can cause aneurysms
number of factors
- developmental
- degenerative
- traumatic
- infections
what type of aneurysms are the commonest?
abdominal aortic aneurysms (AAAs)
what can be a consequence of an aneurysm?
- peripheral vascular disease
- ruptured vessels
Widening of lumen of blood vessel - walls become weak
- Release MMPs
- Dangerous as thinning and weakening of BV can result in rupture
Can develop in cardiac wall
angina pectoris
medical term for chest pain or discomfort due to coronary heart disease. It occurs when the heart muscle doesn’t get as much blood as it needs
process of angina pectoris
- Atherosclerosis in BV (particularly coronary arteries), decrease in O2 and nutrients to myocardial tissue
Inc in metabolic demands of heart (activity, shock, emotions) can cause angina pectoris
treatment for angina pectoris
Take medication and rest and usually resolved
myocardial infarction
Complete obstruction to myocardial muscle (necrosis)
- Infarction-loss of blood supply; oxygen; nutrients
what occurs to the myocardial muscle as a result of myocardial infarction?
coagulation necrosis
- Outline of cell the same, nuclei’s smaller and breaks up so disappears
- Only have outline of cell left
and if survive then healing by granulation tissue
- fibrous tissue (different function)
why is anaerobic respiration ineffective for myocardial muscle?
lasts only a few mins cannot keep up with high metabolic demands of heart
what happens to cells in coagulation necrosis
Cells retain outline so can be identified
- brighter, muscle striations gone
Cytoplasm becomes darker
Remains of nuclei
Striations lost
Inflammatory cells
- Beginning of inflammation and tissue
- Neutrophils the first to arrive
- Then macrophage later - phagocytosis - take away necrotic tissues
- No more empty spaces
Granulation tissue
- macrophages, fibrous tissue replaces muscle fibres (collagen made from fibroblasts) capillaries - blood (rapidly dividing cells)
- Number of BV decrease as inflammation decreases, less muscle mainly fibrous tissue
what are the inflammatory cells which arrive during coagulation necrosis and in which order?
- Neutrophils the first to arrive
- Then macrophage later - phagocytosis - take away necrotic tissues
No more empty spaces in tissue
2 acute coronary syndromes
- angina pectoris
- myocardial infarction
what is a chronic coronary syndrome?
congestive heart failure
congestive heart failure usually follows on from…
- ischemic heart disease (coronary heart disease)
- hypertension
- valvular heart disease
what happens in congestive heart failure?
- ventricular hypertrophy
- oedema (at extremities e.g. ankles)
- chronic venous congestion (CVC) of lung and liver (depending on side of heart which has the failure)
what is chronic venous congestion?
increased volume of blood in a particular tissue
- Passive process which is the resulting from impaired outflow from a tissue
pathophysiology of congestive heart failure
Hypertrophy of myocyte (adaptation)
- resistance of forward flow of heart into circulation
- Heart needs to pump stronger with more force
- Become larger in size (not hyperplasia)
- 2/3 times thicker of normal thickens of ventricular wall
Capillaries do not increase in number
Heart may reach 2-3 times weight of normal
Increased metabolic demands; ischemia.(as cells larger)
Injury to myocyte as a result of ischemia
Apoptosis, heart failure
3 pathologies of blood vessels
- Hamartomas
- kaposi sarcoma
- angiosarcoma
what are the features of Hamartomas?
- Developmental
- Normal tissue in abnormal site or number
where do most haemangiomas occur?
60% in head and neck
what are haemangiomas?
Collection of blood vessels (types of hamartoma)
- Large red fleshy swelling in head and neck
- Alarming for parents
rapid growth during the first few weeks of life
usually regress over the first 10 years
- usually begin regress after 6 months
don’t disappear – left with red lump/mark
what are the 3 types of vascular malformations?
- capillary (lots of little capillaries)
- cavernous (larger spaces filled with BVs)
- Sturge Weber Syndrome
valscular malformations
- Common haemangiomas
dark purple bulges on mucosa - Present at birth and persist during life.
May become more noticeable in elderly
- oral mucosa becomes thinner (atrophy) much more noticeable
- Trauma can cause them to bleed in size - increase in size
Intraosseous malformations may occur
sturge weber syndrome
- Extrinsic haemangioma formations
- Extend to mid line but don’t cross
- Distribution follows nerves
E.g. trigeminal in face
why is a haemangioma in the jaw bone bad?
extraction with lake of blood under
- need specialised hospital setting
aetiology of kaposi sarcoma
Herpes virus 8 (HHV-8)
what is kaposi sarcoma?
Multi-focal low-grade sarcoma of lymphatics and blood vessels
- Almost all oral KS are in HIV-infected patients.
what is the treatment like for kaposi sarcoma?
treatment 90% of cases are controlled (still present)
Immune deficiency- role in carcinogenesis
- Healthy immune reaction is important for control of many viruses - esp oncogenic viruses
Immune suppression due to organ transplant is a risk
what is angiosarcoma?
many malignant tumour cells and blood vessels
- rare
- aggressive cancer
benign cardiac tumours
myxoma
lipoma
rare
malignant cardiac tumours
angiosarcoma
rare
a way in which cardiac tumours can arise
Local extension of tumours from the thoracic cavity such as bronchogenic carcinoma
- Can be around the heart and spread into the heart itself
how can someone get valvular heart disease?
- Congenital or acquired
Acquired may be a result of other cardiac diseases such as ventricular hypertrophy
what can valvular heart disease pathology result in?
Stenosis (injury to valve)
- Cannot open properly
- Forward flow impaired
Insufficiency (many causes)
- Closing of valve impaired
- Regurgitation of blood back into the chamber it came from
Vegetations.
- Lumps on cusps of valves
what is the commonest of all valvular conditions?
calcific aortic stenosis
process of calcific aortic stenosis
Dystrophic calcium deposits as a result of tissue inflammation, hyperlipidaemia.
- Tissue damage on valves
- Calcium deposited here due to inflammation
Narrowing of the valvular orifice
- Valve needs to be thin to function properly – stiff now (difficult to open and close)
treatment of calcific aortic stenosis
valve replacement
need to be on anticoagulants (can lead to bleeding on treatment)
what is calcific aortic stenosis
Dystrophic calcium deposits as a result of tissue inflammation, hyperlipidaemia.
what is rheumatic heart disease a result of?
rheumatic fever
rare in the western world
what does rheumatic heart disease mainly effect?
valves
cross reaction between immune system and valves of heart
what is rheumatic heart disease?
cross reaction between immune system and valves of heart
- Host immune reaction against Streptococcus A antigens that cross react with host proteins
(Antigens formed against Strep A)
Damage caused by a combination of type 2 (antigen-antibody) and 4 (cell mediated reactions) reactions
results of the cross reaction between immune system and valves of heart in rheumatic heart disease
- Inflammation (macrophages and lymphocytes) of endocardium and valves results in fibrinoid necrosis on the surface
- Vegetations formed along the lines of closure
- Thickening and fusion , calcification of valves
- Aortic dilation; atrial fibrillation, thrombi formed on wall of atrium
- Susceptible to developing infective endocarditis (likely)
what is infective endocarditis?
Microbial infection of heart valves
Source can come from oral cavity - poor oral hygiene
- Oral pathogens may be implicated
Streptococcus viridens; Staphylococci aureus
what valves are particularly susceptible to infective endocarditis?
damaged or prosthetic valves
what forms on the cusps of valves in infective endocarditis?
vegetations
contain fibrin, inflammatory cells and infective pathogens
- Soft and friable and can break of and enter circulation to infect other areas of body
- Can cause infective emboli
