Cellular Adaptation and Atrophy Overview

Cellular Adaptation

• Cellular adaptation is a new, steady altered state that allows cells to survive and continue to function in abnormal environments.
• Adaptations are reversible changes in cell number, size, phenotype, metabolic activity, or function in response to environmental changes.
• The process can progress to significant cell injury if the stress isn't relieved.

Atrophy

• Atrophy is a decrease in the size of an organ or tissue due to a decrease in cell size and/or number.
• Atrophic cells shrink due to loss of cell substance.
• Atrophic cells may have diminished function but are not necessarily dead. Continued stress can lead to cell death via apoptosis.
• Mechanisms of atrophy include decreased protein synthesis and increased protein degradation in cells. Protein degradation mainly occurs via the ubiquitin-proteasome pathway.

Atrophy: Mechanisms

• Nutrient deficiency and disuse can trigger the ubiquitin-proteasome pathway.
• This pathway activates ubiquitin ligases that attach ubiquitin to cellular proteins, thus targeting the protein for degradation in proteasomes.
• Atrophy is also accompanied by increased autophagy (cellular "self-eating") in which the cell consumes its own components and may result in increased autophagic vacuoles.
• Some of the remaining debris can persist as residual bodies within the cell (eg., lipofuscin).

Atrophy: Causes

• Reduced workload
• Inadequate nutrition
• Ageing
• Loss of innervation
• Reduced blood supply
• Loss of endocrine stimulation

Atrophy: Types

• Physiological atrophy: Natural reduction in size of organs, tissues (e.g., thymus in adults, ductus arteriosus in infants, gonads in old age).

• Pathologic atrophy: Reduction in organ/tissue size due to disease e.g., starvation, chronic inflammation, cancer, ischemia (reduced blood supply).

  • Generalized atrophy: Reduction in the size and function of entire organs or organ systems (e.g., due to starvation).
  • Localized atrophy: Reduction in the size of a specific area or organ (e.g., due to ischemia).

• Ischemic atrophy (e.g., kidneys in atherosclerosis)

• Disuse atrophy (e.g., muscles in a cast)

• Neuropathic atrophy (e.g., muscles due to nerve damage)

• Endocrine atrophy (e.g., tissues due to hormonal deficiency)

• Pressure atrophy (e.g., tissue due to prolonged pressure)

Hypertrophy

• Hypertrophy is an increase in the size of cells, leading to an increased size of the organ.
• No new cells are created; existing cells simply enlarge.
• Cells containing more structural proteins and organelles. Increased workload and hormonal stimulation can cause hypertrophy.
• Cells capable of division can respond to stress by hypertrophy and hyperplasia.
• Pure hypertrophy affects mainly striated muscles (e.g. heart, skeletal muscle) as well as some stable cells (e.g., liver, kidney).

Hypertrophy: Causes

• Increased functional demand or hormonal stimulation
• In both cases, it's caused either by increased functional demand or hormonal stimulation.

Hypertrophy: Types

• Physiologic hypertrophy: (e.g., skeletal muscle hypertrophy with exercise). Increased uterine size during pregnancy. Breast tissue enlargement during pregnancy.
• Pathologic hypertrophy: Increase in size of an organ due to disease or abnormal stimulation. Example: enlarged left ventricle in response to high blood pressure.

Hyperplasia

• Hyperplasia is an increase in the number of cells in an organ or tissue.
• It occurs through increased cell proliferation of existing cells, differentiated cells or in instances progenitor cells.
• Hyperplasia often results from either hormonal stimulation or tissue loss.
• Many labile cells and stable cells can undergo hyperplasia, unlike permanent cells.

Hyperplasia: Causes

• Hormonal stimulation: Ex., increased breast and uterine smooth muscle during puberty and pregnancy.
• Tissue loss: Ex., regeneration of liver tissue after surgical removal of parts of it.

Hyperplasia: Types

• Physiologic hyperplasia: (e.g. breast at puberty, pregnancy; uterus during pregnancy; compensatory liver increase after removal)
• Pathologic hyperplasia: (e.g. hormonal imbalance in endometrium potentially leading to abnormal periods and cancer risk; viral infections like HPV).

Metaplasia

• A reversible change where one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type.
• Often due to chronic irritation, chronic inflammation, or vitamin A deficiency.

Metaplasia: Causes

• Chronic irritation (e.g., cigarette smoke, stones)
• Chronic inflammation
• Vitamin A deficiency

Metaplasia: Types

• Epithelial Metaplasia:
  • Squamous metaplasia (columnar epithelium replacing squamous epithelium, e.g., in respiratory passages or cervix; Barrett’s esophagus)
  • Columnar metaplasia (squamous epithelium replacing columnar epithelium, e.g., in Barrett’s esophagus)
• Mesenchymal metaplasia: (fibroblast transforming into cartilage or bone cells. Eg. Myositis ossificans.)

Cellular Aging

• Cellular aging is a progressive decline in the life span and functional activity of cells.
• It's caused by genetic abnormalities, accumulation of cellular and molecular damage and continuous exposure to exogenous factors.

Cellular Aging: Mechanisms

• Telomere shortening
• DNA damage and mutations
• Defective protein homeostasis
• Persistent inflammation