- Clinical science
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 learning card provides an overview of the main cellular adaptive mechanisms and their different consequences in the human body.
Definition: Changes experienced by cells in response to physiological or pathological stimuli. These changes usually make cells more tolerable an adverse environment to which they are exposed.
|Definition||Forms and examples|
|Atrophy|| || |
|Anaplasia|| || |
| || |
Ischemic cell injury: Injury due to a lack of oxygen
- Decreased venous drainage (see for details)
- Variable vulnerability: organs have different oxygen demand, oxygen expenditure, and susceptibility to hypoxic damage.
- Metabolic and nutritional causes
- Physical causes
- Autoimmune diseases: immune responses against the body's own cells (e.g., , )
- Genetic defects: misdirect cell metabolism (e.g., cystic fibrosis (CFTR gene), (Xq28 gene), )
- Damage induced by medical therapy and chemicals
- Biological causes
- Definition: Decreased blood supply that cannot meet the oxygen demands of an organ or tissue.
- Decreased arterial perfusion → e.g., atherosclerosis, thromboembolism
- Decreased venous drainage → e.g., testicular torsion, ovarian torsion ,
- intravascular volume → decreased delivery of oxygen to tissue → ischemia (e.g., hemorrhage) → decreased
- cardiac tamponade) → decreased left ventricular function → decreased forward flow of blood → decreased delivery of oxygen to tissue → ischemia (e.g.,
- septic, neurogenic, and anaphylactic shock) → systemic vasodilation → peripheral pooling of blood → decreased delivery of oxygen to tissue → ischemia (e.g.,
- For more specific details see the learning card on .
|Organs most susceptible to ischemia|
|Organ||Specific structure||Clinical significance|
|Kidney|| || |
|Liver|| || |
Cell injury: cellular damage due to internal and external environmental changes
Early stage (reversible)
- Swelling of the cell; (e.g., hydropic degeneration; ): tissue ischemia → decreased ATP production → decreased Na+/K+ ATPase and Ca2+ pump activity → diffusion of Na+ and water into the cell → cellular swelling
- Clumping of nuclear chromatin
- Detachment of ribosomes and polysomes → decreased protein synthesis
Late stage (irreversible) → results in cell death
- Degradation of phospholipids in the plasma membrane → rupture of the cell membrane → release of cytosolic enzymes into the serum and influx of Ca2+into the cytoplasm → activation of lysosomal enzymes → autolysis
- Rupture of lysosomes and release of lysosomal enzymes → autolysis
- Increased mitochondrial membrane permeability
- Nuclear changes
- Early stage (reversible)
- Cell death: irreversible damage that renders cells unable to carry their function. It results in either apoptosis or necrosis.
|Pathophysiology|| || |
- Description: programmed cell death (physiological cell turnover)
- DNA damage
- Hypoxia and other types of exogenous damage to the cell (radicals, irradiation, toxins)
- Growth factor withdrawal
- Specific signals such as TNF-alpha and ligands (TRAIL, FasL) activate the apoptotic program of the cells via binding to death receptors (DR 4/5, FAS, TNF-R).
- Cytotoxic T cells, which recognize a pathogen on the target cell
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
Caspases: enzymes from the group “Cysteine-ASpartic ProteASES” that cleave proteins and peptides and attack the cell membrane, nucleus, and cytoplasm
- Extrinsic pathway (death receptor pathway): extracellular ligands (e.g., TNF-α, TRAIL, or FasL) bind to a death receptor on the cell surface.
Intrinsic pathway (mitochondrial pathway): intracellular stimuli activate the mitochondrial pathway.
- p53 is activated through DNA damage (e.g., chemical toxins, radiation).
- p53 leads to an intracellular increase of proapoptotic proteins (e.g., Bax or Bad).
- These proteins increase the permeability of the mitochondrial outer membrane, e.g., through the formation of a membrane channel by the heterodimer Bax/Bad.
- Cytochrome c enters the cytosol from mitochondria through the membrane.
- Cytochrome c binds to APAF-1 (apoptotic protease activating factor-1) in the cytosol.
- The complex of cytochrome c and APAF-1 converts procaspase 9 into active caspase 9.
- Caspase 9 activates executioner caspases such as caspase 3.
- Association: Caspase 8 is not only a part of the extrinsic pathway but also stimulates the intrinsic pathway by altering the permeability of the inner mitochondrial membrane.
- Histopathological findings
Proteins of the Bcl-2 family can have opposite effects, e.g., Bad and Bax have a proapoptotic effect, whereas Bcl-2 and Bcl-xL have an antiapoptotic effect!
Abnormal regulation of apoptosis
- Follicular lymphoma → translocation t(14;18) → Blc-2 (regulator of apoptosis) on chromosome 18 is translocated to the immunoglobulin heavy chain locus on chromosome 14 → overexpression of Bcl-2 → abnormal lymphocytes never died and produce cancer.
- Burkitt lymphoma → translocation t (8;14) → c-myc (nuclear regulator protein) on chromosome 8 is translocated to the immunoglobulin heavy chain locus on chromosome 14 → overexpression of c-myc → associates with Bcl-2 → overexpression of c-myc and Bcl-2 → lymphoma
- Infection with high-risk strains of HPV (e.g., HPV-16 and HPV-18)
- → HPV encodes for protein E6 → E6 binds to p53 → inactivation of p53 → inability of p53 to arrest the cell cycle and to activate DNA repair genes → proliferation of abnormal cells → low-grade dysplasia → high-grade dysplasia → carcinoma in situ → invasive cervical carcinoma
- → HPV encodes for protein E7 → E7 binds to Rb → inability of Rb to bind to E2F and arrest the cell cycle → proliferation of abnormal cells → low-grade dysplasia → high-grade dysplasia → carcinoma in situ → invasive cervical carcinoma
- Infection with high-risk strains of HPV (e.g., HPV-16 and HPV-18)
- Short description: collective term for unprogrammed cell death and tissue destruction
- Never physiologically induced
- Always associated with an inflammatory reaction
- Process: : cell damage → nuclear changes (pyknosis, karyorrhexis, karyolysis) → cell swelling, cell wall protrusions, cell organelle destruction → cell bursts → inflammation → degradation of the necrotic tissue by leukocytes → organization of granulation tissue
Types of necrosis
|Coagulative necrosis||Liquefactive necrosis||Fibrinoid necrosis||Caseous necrosis||Fat necrosis||Gangrenous necrosis|
|Definition|| || || |
|Microscopic appearance|| || || |
|Example|| || || || |
- Short description: increased storage of triglycerides, cholesterol, and complex lipids in cells
- Occurrence: liver, heart, muscles, kidneys
- Histological staining: Sudan stain or oil red O staining, unfixed or formalin fixed, frozen sections
- Metastatic calcification: diffuse calcification of normal tissue
- Dystrophic calcification: localized calcification of degenerated inflammatory sites or necrotic tissues
- Hyaline: : descriptive term used for proteins that appear homogeneously transparent under light microscopy and are eosinophilic in H&E staining (also stain red in the van Gieson's stain). It 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.
|Mallory bodies||Inclusion bodies within the cytoplasm of the hepatocytes that contain intermediate filaments and appear 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|
|Russel bodies||Accumulation of immunoglobulins||Plasma cells in plasmacytoma or chronic inflammation|