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Cellular changes and adaptive responses

Last updated: August 5, 2021

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Cellular adaptation is the ability of cells to respond to various types of stimuli and adverse environmental changes. These adaptations include hypertrophy (enlargement of individual cells), hyperplasia (increase in cell number), atrophy (reduction in size and cell number), metaplasia (transformation from one type of epithelium to another), and dysplasia (disordered growth of cells). Tissues adapt differently depending on the replicative characteristics of the cells that make up the tissue. For example, labile tissue such as the skin can rapidly replicate, and therefore can also regenerate after injury, whereas permanent tissue such as neural and cardiac tissue cannot regenerate after injury. If cells are not able to adapt to the adverse environmental changes, cell death occurs physiologically in the form of apoptosis, or pathologically, in the form of necrosis. This article provides an overview of the main cellular adaptive mechanisms and their different consequences in the human body.

Overview of cellular adaptation
Definition Forms and examples
  • Degeneration of tissue or organ (e.g., due to malnutrition or hereditary disease)
  • Increased tissue size via enlargement of cells (due to an increase in organelles and structural proteins)
  • Controlled proliferation in form of elevated reproduction rate of stem cells and differentiated cells → ↑ cell number → ↑ tissue mass
  • Malignant transformation
  • As a response to chronic stress, stem cells get reprogrammed into another type of epithelium (e.g., squamous metaplasia) that is more tolerable to the adverse environment.
  • May completely regress or lead to a persistent insult and malignant transformation (dysplasia; considered precancerous)


  • Rapid division and an increase in the number of cells
  • Complete regeneration: Tissue loss is both homogeneously functionally and structurally replaced.
  • Incomplete regeneration: Tissue loss is replaced by tissue of an inferior quality.



Organs most susceptible to ischemia
Organ Specific structure Clinical significance
  • Proximal tubule (straight segment in the medulla)
  • Thick ascending limb (in the medulla)
  • Ischemic tolerance time: the time after which ischemia causes irreversible tissue damage
    • Skin: 12 h
    • Musculature: 6–8 h
    • Neural tissue: 2–4 h




Oxygen toxicity [7][8]

Reperfusion injury

Metal storage diseases

Chemical/drug toxicity

Cell death is the irreversible damage that renders cells unable to carry their function. It results in either apoptosis or necrosis.

Apoptosis vs. necrosis

Overview of apoptosis and necrosis
Characteristics Apoptosis Necrosis
  • Programmed cell death (ATP-dependent process)
  • Does not cause an inflammatory response
  • Nonphysiologic cell death
  • Causes an inflammatory response

General information

Signaling cascade

  • Apoptosis can be initiated via two different pathways: the extrinsic pathway (through external stimuli) or the intrinsic pathway (through internal stimuli).
  • General sequence of events: stimulus → activation of initiator caspases activation of executioner caspases apoptosis

Extrinsic pathway (death receptor pathway)

Can be activated via 2 mechanisms:

Intrinsic pathway (mitochondrial pathway)

Proteins of the Bcl-2 family can have opposite effects: Bad, Bax, and Bak have a proapoptotic effect, whereas Bcl-2 and Bcl-xL have an antiapoptotic effect.

Abnormal regulation of apoptosis

Tumor suppressor genes that regulate the cell cycle and cell death can mutate and allow cells to remain alive even if they have abnormal genes that can cause cancer.


Types of necrosis

Characteristics of necrosis
Type Definition Pathophysiology Microscopic appearance Example
Coagulative necrosis
  • A type of necrosis caused by tissue ischemia that occurs in most tissues except the brain.
  • Preserved, anuclear, eosinophilic cellular architecture
  • H&E: eosinophilic staining due to the binding of eosin stain to denatured intracellular proteins
  • Myocardial, splenic, hepatic, and renal infarction
  • Gangrene
  • Organ damage caused by acidic solutions
Liquefactive necrosis
  • Release of hydrolytic enzymes from neutrophilic lysosomes that digest the affected tissue
  • Early: macrophages and cellular debris
  • Late: cavitations or cystic spaces
  • Bacterial infections: cellular debris and neutrophils
Fibrinoid necrosis
  • Visible damage: thick walls with fragments of embedded cellular debris, serum, and fibrin
  • Affected necrotic areas stain intense red.
Caseous necrosis
Fat necrosis
  • A type of necrosis in which adipose cells die off prematurely, either caused by an enzymatic reaction, or traumatic injury.
Gangrenous necrosis



Overview of calcification
Metastatic calcification Dystrophic calcification
  • Diffuse calcification of normal tissue
Involved tissues
  • Normal tissues of kidney, lung, gastric mucosa, and blood vessels
  • Involved tissues rapidly lose acid.
  • Increased pH levels promote calcium deposition.
  • Abnormal necrotic tissues or degenerated inflammatory sites

Associated conditions/tissue

Serum calcium findings
  • Usually increased
  • Usually normal



  • Hyaline
    • A type of protein that is eosinophilic on H&E staining (also stains red on van Gieson stain) and appears homogeneously transparent under light microscopy
    • Can be used to differentiate between intracellular and extracellular hyaline
  • Hyalinization: replacement of normal tissue by proteins that have an eosinophilic, homogenous, translucent appearance on H&E staining

Intracellular hyaline

Characteristics of intracellular hyaline

Inclusion bodies

Morphology Occurrence
Mallory bodies Inclusion bodies within the cytoplasm of hepatocytes that contain damaged intermediate filaments and appear eosinophilic (pink) on H&E stain Most common in alcoholic liver disease

Councilman bodies

An eosinophilic remnant of apoptotic hepatocytes with pyknosis Particularly in yellow fever and viral hepatitis
Schaumann bodies Round calcium and protein inclusions in the cytoplasm with laminar stratification Granulomas in sarcoidosis
Russell bodies Accumulation of immunoglobulins Plasma cells in plasmacytoma or chronic inflammation

Extracellular hyaline

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