L30. Cellular adaptations, myocardial hypertrophy and introduction to pathology of the cardiac valves Flashcards
What happens to a normal cell if it is put under some kind of physiological stress? What happens if this fails?
The cell undergoes ADAPTATION
If this fails, the cell is injured
How does the cell decide its response to stress/injurious stimuli?
The cell cycle it has: Labile (has stem cell populations), stable (able to enter if required) or permanent (change or die)
The type of stimulus: growth factor or hormonal, pH changes or mechanical stress
What is a major reaction of cardiac and skeletal muscle to increased work loads or stress?
Hypertrophy
- Increased synthesis of contractile proteins
- increased production of growth factors
- induction of embroynic genes
Define Hypertrophy
What cell types go through this
An increase in the SIZE of cells (no increase in number)
- increased production of intracellular structures
- increased nucleus size (and shape)
- done mainly by permanent cells
Define Hyperplasia: is it always pathological?
What cell types go through this?
An increase in the NUMBER of cells
- when STEM CELLS are stimulated to divide by either hormonal or growth factor
- can be physiological or pathological
- done by labile cells (active stem cell population) or stable cells
Often occurs at the same time as hypertrophy
What is an example of hyperplasia being a physiological process?
Cyclical Hormonal: the endometrium gets bigger and stretches out with more glands in the tissue during menstruation.
Give an example of a pathological hyperplasia
Parathyroid hyperplasia eg. High calcium concentrations stimulate the excessive release of parathyroid hormone leading to the parathyroid to increase cellular concentrations
Give an example where hypertrophy and hyperplasia occer together
Graves Disease where a rogue antibody stimulates the thyroid leading to lost colloid, far more cells which are much bigger in size
Define Metaplasia
A REVERSIBLE change in which one adult cell type is replaced by another adult cell type
Where does metaplasia occur frequently and to what stimulus?
At junctions between different epithelial types (eg. cervix) and the stimulus is usually an altered environment
Why does metaplasia occur?
The new phenotype is often protective against injury in the new environment or have no benefit at all and hence metaplasia can be both pathological or physiological
What is a physiological example of metaplasia?
The onset of menarche for women means the swelling of tissues which exposes the endocervical mucosa to the acidic vagina: this changes the glandular, columnar epithelium into a stratified, squamous epithelium
What is an example of pathological metaplasia?
Gastro-oesophageal reflux disease (Barrett-oesophagus) where bile acids are brought up into the oesophagus the stratified squamous epithelium of the oesophagus changes to an intestinal type with the mucous secreting goblet cells in it.
This actually shows no benefit to the disease and may be a pathway to cancer.
What is the difference between hyperplasia + metaplasia and Neoplasia?
Hyperplasia + Metaplasia is CONTROLLED and REVERSIBLE (with removal of the stimulus) with a CHANGE in gene expression and is often BENIGN (may be a risk factor for neoplasia due to the frequency of divisions)
Neoplasia is DYSREGULATED and occurs in the ABSENCE of a stimulus. It occurs due to a genetic MUTATION and can be either benign or malignant.
Define Atrophy. Is it reversible?
A decrease in the cell or organ size (opposite of hypertrophy)
It is reversible if it is not accompanied by cell death and fibrosis
When does atrophy occur?
When there is a loss or decrease of normal growth stimulus.
- diminished workload, blood supply, innervation or hormonal stimulation
- can occur simply due to ageing
What is the difference between physiological and pathological myocardial hypertrophy?
Physiological = Developmental Hypertrophy due to growth in childhood or can be in response to exercise. Characterised by growth of the ventricles in proportion to the chamber, increased capillaries, REVERSIBLE and no loss of function
Pathological: hypertension, valvular disease
Characterised by growth with reduced or enlarged cavity, REDUCED FUNCTION and deposition of matrix (fibrosis) and IRREVERSIBLE
What is the difference between concentric and eccentric hypertrophy?
Concentric due to increased pressure leads to fatter cells with increased diameter in parallel. Increased wall thickness with smaller cavity
Eccentric due to volume overloads with the elongation of the myocytes in series. Leads to a bigger cavity and normal (or occasionally thinned) walls
What are the ways to diagnose hypertrophy?
ECG
Heaving and/or displaced apex beat
What are the normal wall thicknesses of the Left and Right Ventricles?
LV < 15 mm
RV < 5mm
Wall thickness measurement (not inclusive of the papillary muscle taken from a transverse section through the middle of the heart)
Eccentric hearts are compared by the weight of the heart. What is the normal heart weight dependent on? What are the normal values?
Depends on the body mass/height
Women usually have 400g and men 500g
What are the microscopic features of myocardial hypertrophy?
Enlarged, rectangular (box shaped) nuclei
Bi-nucleated
Increased amount of connective tissues
What are some complications of myocardial hypertrophy?
Impaired perfusion and increased demand leading to ischaemia
Increased LV stiffness and impaired diastolic filling
What are other causes of myocardial hypertrophy?
Iscahemic heart disease
Genetic Causes
Infiltrative Diseases
What are some consequences of cardiac failure?
Cardiomegaly
Pulmonary oedema
Nutmeg liver congestion
Peripheral Oedema
What are the three different ways to classify valvular disease?
- By the pathological process (Eg. degenerative or infectious etc)
- By the result (Eg. stenosis or regurgitation)
- By the affected valve (Eg. Aortic, Mitral)
What are complications of valvular disease?
Altered cardiac blood flow: angina, syncope, myocardial hypertrophy, cardiac failure, arrhythmia
Thrombosis
Infective Endocarditis
How does rheumatic heart disease cause valve problems?
By an aberrant immune response to Streptococcus produces molecular mimicry so antibodies attack the valves leading to chronic inflammation and fibrosis causing stenosis or regurgitation.
What are the symptoms of infective endocarditis?
Fever, worsening or new onsets of murmurs, symptoms of embolism
How do bacteria get into the blood stream to cause infective endocarditis?
Dental work, invasive procedures/surgery, IV drug use
What is myxomatous mitral valve disease?
Usually due to ageing or congenital disease (collagen diseases) that leads to mitral valve prolapse - the valve leafs sit up away from the valve opening.
What is denerative bicuspid valves
Predisposition to degenerative calcification of the valves leading to regurgitation or stenosis depending on the damage caused
