Cellular Adaptation Reactions

Cellular Adaptation Reactions

• All organ injuries and clinical diseases stem from derangements in cell structure and function.
• Rudolf Ludwig Carl Virchow lived from 1821–1902.

Cellular Responses to Injury

• These include cellular adaptations, reversible versus irreversible cell injury, intracellular accumulations, calcifications, and cellular aging.
• Cellular adaptations include hyperplasia, hypertrophy, atrophy, and metaplasia.

Cellular Responses by Stimulus (I)

• Altered physiologic stimuli lead to cellular adaptation.
• Increased demand or stimulation can cause hyperplasia or hypertrophy.
• Decreased demand or lack of nutrients can cause atrophy.
• Prolonged physical or chemical irritation can cause metaplasia.

Cellular Responses by Stimulus (II)

• Pathologic stimuli result in cell injury or damage.
• Acute, self-limited stimuli cause acute reversible cell injury.
• Progressive and severe stimuli cause irreversible cell injury, leading to cell death.
• Mild but chronic stimuli cause subcellular alterations in the organelles.

Cellular Responses by Stimulus (III)

• Inherited or acquired metabolic alterations and chronic injury can result in intracellular accumulations (proteins, lipids, carbohydrates) and calcification.
• Cumulative sublethal injury can lead to cellular aging.

Cellular Adaptation Reactions: Definitions

• Adaptation is a reversible functional and structural response to severe physiologic stresses and some pathologic stimuli resulting in a new but altered steady state.
• Hyperplasia is an increase in the number of cells.
• Hypertrophy is an increase in the size of cells or an organ.
• Atrophy is a decrease in size and metabolic activity.
• Metaplasia is the replacement of adult cells by another adult cell type.

Hyperplasia

• Physiologic hyperplasia is hormone-induced, increasing tissue's functional capacity for periodic requirements. An example is the breast.
• Compensatory hyperplasia increases tissue mass after damage or partial resection. An example is the liver after hemihepatectomy.
• Pathologic hyperplasia is induced by hormone imbalance. For example estrogen and progesterone imbalance can cause endometrial hyperplasia. Also, androgen imbalance can cause prostatic hyperplasia.
• Viral infections can induce it. For example papilloma virus can cause warts.

Hypertrophy

• Enlargement of cells occurs leading to the increased size of an organ.
• Synthesis of the structural components of the cell is demanded to ensure the greater mass.
• Mainly combined with hyperplasia, except for non-dividing cells, although the cardiac and skeletal muscle in adults is suggested to be non-dividing and respond by hypertrophy only, the concept is changing.
• Increased functional demands can cause muscle hypertrophy.
• Stimulation by hormones or growth factors and hypertrophy of the myometrium can occur during pregnancy.
• Increased production of cellular proteins is due to mechanical sensors triggered by increased workload, resulting in the production of growth factors (TGF-beta, IGF-1), and vasoactive substances (endothelin-1, angiotensin II).
• Physiologic examples include muscle during training and the myometrium during pregnancy.
• Pathologic examples include heart muscle in arterial hypertension or valvular heart disease.
• Physiologic hypertrophy mainly involves the phosphoinositide 3-kinase (Akt) pathway.
• Pathologic hypertrophy mainly involves signaling downstream of G-protein coupled receptors.
• Hypertrophy can be associated with a switch of contractile proteins from adult to fetal and neonatal forms where the alfa isoform of mysin heavy chain is replaced by beta.
• Hypertrophy can be associated with the re-expression of some genes like atrial natriuretic factor.

Outcome of Cardiac Hypertrophy

• Cardiac hypertrophy is reversible if the cause is eliminated.
• Persistent cause leads to progressive changes and heart failure.
• Adaptation to stress can progress to cell injury if stress isn't relieved.

Atrophy

• Atrophy is the shrinkage of cell or organ, and can be physiologic or pathologic.

Mechanisms of Atrophy

• Atrophy is a reduced size of an organ or tissue due to decreased cell size and number.
• The biological aim is to ensure cell survival under difficult conditions by reducing metabolic needs.
• Atrophy involves decreased cell size, decreased number of organelles, decreased protein synthesis due to reduced metabolic activity, and increased degradation via the ubiquitin-proteasome pathway or autophagy.
• Ubiquitin-proteasome pathway involves nutrient deficiency activating ubiquitin ligases, marking proteins for degradation in proteasomes.
• Autophagy involves the cell destroying its own components to obtain nutrients, forming autophagic vacuoles that fuse with lysosomes, leaving digestion-resistant debris (residual bodies) like brown lipofuscin, related to brown atrophy (atrophy associated with brown discoloration of tissue).

Causes of Atrophy

• Decreased workload, like immobilization, results in muscle atrophy and osteoporosis of disuse.
• Other causes include denervation, decreased blood flow, lack of nutrients, lack of appropriate endocrine stimuli, aging, and pressure-related compromised blood supply (ischemia).

Outcomes of Atrophy

• The changes of atrophy can be reversible.
• Prolonged causative factors can lead to cell death by apoptosis, like in muscle with diminished blood flow or endocrine organs after hormone withdrawal.

Metaplasia

• Metaplasia is when one mature tissue is replaced by another to improve the tissue's survival but may lead to a loss of specific function and potential cancerogenesis under certain conditions.
• Squamous metaplasia in the bronchial epithelium is associated with pre-cancerous change

Types of Metaplasia

• Epithelial metaplasia includes squamous metaplasia in the bronchial epithelium of smokers or those with vitamin A deficiency, and Barrett’s oesophagus.
• Mesenchymal metaplasia includes myositis ossificans.

Mechanisms of Metaplasia

• Metaplasia is ensured by reprogramming of stem cells present in the normal tissues (not by direct change of cell type).
• This involves tissue destruction, activation of stem cells or undifferentiated mesenchymal cells, cytokines, growth factors, extracellular matrix, expression of certain genes, and differentiation of stem cells along a new pathway.