Cellular changes and adaptive responses

Last updated: September 5, 2023

Summarytoggle arrow icon

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.

Cellular adaptationtoggle arrow icon

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.

Cell injurytoggle arrow icon



Ischemiatoggle arrow icon

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

Free radical injurytoggle arrow icon




Oxygen toxicity [7][8]

Reperfusion injury

Metal storage diseases

Chemical/drug toxicity

Overview of cell deathtoggle arrow icon

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

Apoptosistoggle arrow icon

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.

Necrosistoggle arrow icon


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

Cellular inclusionstoggle arrow icon

Intracellular accumulations result from increased intracellular storage of substances and represent a manifestation of metabolic derangement.


  • Endogenous
  • Exogenous: storage of substances not naturally occurring in the body (e.g, tattoo ink, carbon from coal dust or smoke)

Intracellular accumulation of lipids

Intracellular accumulation of triglycerides (steatosis)

Intracellular accumulation of cholesterol

Intracellular accumulation of carbohydrates

Intracellular and extracellular accumulation of proteins

Intracellular accumulation of hyaline

  • Hyaline: intracellular or extracellular protein deposition (e.g., intracellular hyaline in hepatocytes; extracellular hyaline in arterial walls) that appears eosinophilic on H&E staining (stains red on Van Gieson stain)
Characteristics of intracellular hyaline

Types of inclusion bodies

Morphology Occurrence
Mallory bodies

Councilman bodies

Schaumann bodies
Russell bodies

Lewy bodies

Extracellular accumulation of hyaline

Intracellular and extracellular accumulation of minerals

  • Definition: increased storage of minerals in cells

Intracellular and extracellular accumulation of calcium

Overview of calcification
Metastatic calcification [9] Dystrophic calcification [10]
  • Diffuse calcification (intracellular and extracellular) of otherwise noncalcified tissue
  • Localized calcification (intracellular and extracellular) of otherwise noncalcified tissue
Involved tissues
  • Degenerative or necrotic tissues or degenerative inflammatory sites

Clinical significance

Serum calcium findings
  • Usually increased
  • Usually normal


Intracellular accumulation of iron

Intracellular accumulation of copper

  • Definition: increased storage of copper in cells
  • Characteristics: free ions or storage via protein binding
  • Clinical significance: Wilson disease

Intracellular accumulation of pigments

Referencestoggle arrow icon

  1. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health.. International journal of biomedical science : IJBS. 2008; 4 (2): p.89-96.
  2. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews. 2010; 4 (8): p.118.doi: 10.4103/0973-7847.70902 . | Open in Read by QxMD
  3. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine. 2018; 54 (4): p.287-293.doi: 10.1016/j.ajme.2017.09.001 . | Open in Read by QxMD
  4. Eltzschig HK, Eckle T. Ischemia and reperfusion—from mechanism to translation. Nat Med. 2011; 17 (11): p.1391-1401.doi: 10.1038/nm.2507 . | Open in Read by QxMD
  5. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury.. International review of cell and molecular biology. 2012; 298: p.229-317.doi: 10.1016/B978-0-12-394309-5.00006-7 . | Open in Read by QxMD
  6. Ahmad I, Barnetson RJ, Krishna NS. Keratinizing Squamous Metaplasia of the Bladder: A Review. Urol Int. 2008; 81 (3): p.247-251.doi: 10.1159/000151398 . | Open in Read by QxMD
  7. Michalopoulos GK. Liver regeneration.. J Cell Physiol. 2007; 213 (2): p.286-300.doi: 10.1002/jcp.21172 . | Open in Read by QxMD
  8. Guerini D. The Ca2+ pumps and the Na+/Ca2+ exchangers.. Biometals. 1998; 11 (4): p.319-30.
  9. Le C, Bedocs PM. Calcinosis Cutis. StatPearls. 2021.
  10. Jeon S-W, Park Y-K, Chang S-G. Dystrophic Calcification and Stone Formation on the Entire Bladder Neck After Potassium-titanyl Phosphate Laser Vaporization for the Prostate: A Case Report. J Korean Med Sci. 2009; 24 (4): p.741.doi: 10.3346/jkms.2009.24.4.741 . | Open in Read by QxMD
  11. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2015

Icon of a lock3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer