Cellular Adaptations

Question 1

What are some conditions in which cells are subject to change and what do these changes often include?

Answer 1

- Conditions to which cells are exposed are subject to change
	– Physiological 
	– Pathological  
- Responses include:
	- Adaptive responses if changes are not excessive
		- Metabolic 
		- Structural 
			- Changes in cell size and growth 
			- Changes in cellular differentiation

Question 2

What can cell injury include?

Answer 2

• Cell injury: if the limits of adaptive responses are exceeded or if adaptation is not possible
  
  • Reversible
  • Irreversible: dependent on magnitude and type of injury
    
    • Necrosis
    • Apoptosis

Question 3

What is the principle surrounding cell hypertrophy?

Answer 3

Hypertrophy:

• an increase in the size of existing cells, no cell division
• physiologic or pathologic
• Increased synthesis of structural components
• Due to increased functional demand or stimulation by hormonal or growth factor
• reversible

Question 4

What is the principle surrounding cell hyperplasia?

Answer 4

Hyperplasia:

• increase in the number of cells
• physiologic or pathologic
• due to stimulation by hormonal or GFs
• reversible

Question 5

Explain the difference hyperplasia and hypertropy.

Answer 5

Quite often hyperplasia and hypertrophy occur together.
- Normal thyroid; Grave’s disease
The difference between the two concepts depends on whether or not the calls can divide. Mature cells may be:
- labile
- stable (quiescent)
- permanent
- Labile and stable cells can readily divide - they can undergo hyperplasia
- Permanent cells cannot divide after birth:
- they cannot undergo hyperplasia
- but they can undergo hypertrophy

Question 6

What is atrophy?

Answer 6

Atrophy:

• Cells can decrease in size and activity
  
  • associated with reduction in cellular metabolism and reduced synthesis of structural proteins.
  • cellular components removed by autophagy
• Tissues can decrease in size and activity due to cell death via apoptosis.
• Related to physiological (ie. age-related) or pathological:
  
  • Inadequate nutrition
  • Diminished blood supply
  • Denervation
  • Disuse
  • Loss of endocrine stimulation
  • Pressure
• Atrophic cells may have diminished function but are not dead. In this situation, atrophy is potentially reversible.
• Atrophy of tissue where there has been cell loss and associated fibrosis is not reversible.
• Involution: physiological atrophy involving apoptosis (uterus post partum, thymus)

Question 7

What is metaplasia?

Answer 7

Metaplasia:
- Certain long standing environmental changes have adverse effects on specialised cell types
- Resulting in change from one fully differentiated adult/mature cell type to another fully differentiated adult/mature cell type that is better able to withstand the new environmental conditions
- May be physiological or pathological
- Due to cytokine or growth factor driven reprogramming of the line of differentiation of adult/somatic stem cells
(ie/ squamous metaplasia in bronchial epithelium in smokers)

Question 8

What are some principles of cell biology of adaptive changes?

Answer 8

Cell growth and proliferation are under the control of various growth factors and hormones that act on specific cell surface receptors that are linked to internal signaling pathways which regulate gene transcription

• Adaptive changes are regulated and are not neoplastic (unregulated and autonomous cell proliferation)
• However, neoplastic processes arise from dysregulation of these same pathways
• Hyperplasia in certain situations can confer an increased risk of malignancy, due to increased risk of mutations developing
• Influences that predispose to pathologic metaplasia may also initiate malignant transformation in the metaplastic epithelium

Question 9

What are some causes of valvular disease?

Answer 9

• Congenital abnormalities e.g. bicuspid aortic valve (affects approx. 1% of population)
  
  • Myxomatous mitral valve (genetic or acquired) - affects approx. 2% of population
  • Degenerative changes – calcification
  • Inflammatory
    
    • Infection
    • Immune mediated
  • Other

Question 10

What are some features of abnormalities in valvular disease?

Answer 10

These abnormalities:

- Are not necessarily symptomatic 
- May cause a murmur that can be heard on examination, even if the patient is 	asymptomatic  
- Predispose to infective endocarditis 
- When severe, may cause incompetence and/or stenosis of the valve, depending 	on the disease, leading to various symptoms, commonly related to heart failure  	- Mitral valve disease (stenosis or incompetence) can lead to atrial fibrillation. In 	this situation, thrombi may form in the left atrium and embolise to the brain

Question 11

What are some complications of valvular disease?

Answer 11

Complications can include:

- Infarction
- Abscess
- Valve damage

Question 12

What are some treatments for valve disease?

Answer 12

Stenosis and incompetence are generally treated by some form of surgery, often by replacement of the valve by a prosthetic mechanical valve or a biological valve e.g. porcine. These valve replacements are also susceptible to infective endocarditis. Prosthetic mechanical valves also predispose to thrombosis of the valve, requiring the patient to take anticoagulant drugs to prevent thrombosis and thus embolic complications.

Question 13

What are some features of myocardial hypertrophy?

Answer 13

• May be physiologic (athletes) or pathologic

Pathologic
– Adaptive response to haemodynamic burdens i.e. increased pressure (afterload) or volume loads, to maintain cardiac output

‘Specific’ cardiomyopathies

• Miscellaneous group of diseases that primarily affect the heart muscle, not the result of congenital, valvular, hypertensive, coronary arterial, or pericardial abnormalities
• Genetic, metabolic, toxic, iatrogenic, other causes

Question 14

What is the ventricular response to hemodynamic burdens?

Answer 14

• Concentric hypertrophy (thickened muscle fibres, new sarcomeres synthesised in parallel with the old), develops in situations of increased afterload -> preservation of systolic function for a while, but ultimately
  – Thickened myocardium -> Impaired perfusion -> ischaemia OR Impaired filling in diastole
• Eccentric hypertrophy (lengthened muscle fibres, new sarcomeres synthesised in series with the old) develops in situations of volume load, aids function up to a point, but ultimately also predisposes the myocardium to ischaemia
• As hypertrophy worsens, the ventricle starts to fail, contributed to by associated subcellular changes, microscopic fibrosis and apoptosis related to wall stress, elevated catecholamines and cytokine production
• In most cases, a failing left ventricle eventually becomes dilated (-> displacement of apex beat to left, enlarged heart on chest x-ray) as it is not pumping out sufficient blood -> increased end systolic volume ->-> increased end diastolic volume