- 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|| || |
|Dystrophy|| || |
|Anaplasia|| || |
| || |
- Definition: cellular damage due to internal and external environmental changes
Early stage (reversible) → results in cellular swelling (e.g., hydropic degeneration)
Tissue hypoxia → decreased ATP production:
- Decreased Na+/K+ ATPase → diffusion of Na+ and water into the cell → ↓ passive Ca2+ efflux and cellular/mitochondrial swelling
- Disrupted Ca2+ ATPase pump activity → ↓ active Ca2+ removal from the cytoplasm into the extracellular space → Ca2+ accumulates inside the cell and activates degradative enzymes.
- Low oxygen and ATP result in anaerobic respiration → ↑ lactate and ↓ intracellular pH → denatures proteins and causes clumping of nuclear chromatin
- Detachment of ribosomes and polysomes → decreased protein synthesis
- Tissue hypoxia → decreased ATP production:
Late stage (irreversible) → results in membrane damage and cell death
- Mechanism: 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 and protease (e.g., calpain) → ↑ breakdown of cellular proteins and damage cytoskeleton → autolysis
- Rupture of lysosomes and release of lysosomal enzymes → autolysis
- Increased mitochondrial membrane permeability → cytochrome c release from mitochondria → activates apoptosis
- Nuclear changes
- Early stage (reversible) → results in cellular swelling (e.g., hydropic degeneration)
- Ischemic cell injury: see details below
- Reperfusion injury: see details below
- 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|| || |
Ischemic tolerance time, after which irreversible tissue damage begins to take place
- Skin: 12 h
- Musculature: 6–8 h
- Neural tissue: 2–4 h
- Oxygen is reintroduced to the previously ischemic tissue (oxygen toxicity) → activated endothelial cells and leukocytes generate (ROS)
Cause damage to:
- DNA (via fragmentation)
- Cell membranes: via direct damage and lipid peroxidation → increased permeability
- Mitochondrial membranes: via lipid peroxidation and transition pores → increased permeability
- Cellular proteins
- Microvessels: microvascular injury → increased permeability of capillaries and arterioles → increased diffusion and fluid filtration → tissue swelling
- Recruit and activate platelets → increase coagulation
- Recruit and activate WBCs → worsen the immune response started by ischemia
- Cause damage to:
- WBCs infiltrate the area (in response to ischemic cell damage) → release cytokines → inflammatory response
- WBCs bind to the endothelium of small capillaries → capillary obstruction → worsening of ischemia
- Occurrence: spontaneously or secondary to intervention (e.g., PCI or thrombolytic therapy)
- Pathology: : results in a
- Possible complications (depending on the location of ischemia/reperfusion injury)
- Monitoring and symptomatic treatment
- If affecting limb that is beyond recovery → amputation
|Definition|| || |
|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
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)
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 of the Bcl-2 family (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, forming a wheel-like structure, known as an apoptosome.
- The complex of cytochrome c and APAF-1 converts procaspase 9 into active caspase 9.
- Caspase 9 activates executioner caspases such as caspase 3.
- Shrunken and irregularly shaped cells with membrane blebbing
- The cell detaches from other cells or the extracellular matrix.
- Nuclear changes (pyknosis, karyorrhexis, karyolysis)
- Degradation of the cell into apoptotic bodies
- Phagocytosis by macrophages
- DNA laddering (fragments in multiples of 180 base pairs) is seen on gel electrophoresis
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|| || |
|Caseous necrosis|| |
|Fat necrosis|| || || |
|Gangrenous necrosis|| |
- 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||Dystrophic calcification|
|Description|| || |
|Involved tissues|| |
|Etiology|| || |
|Serum calcium findings|| || |
| || |
- 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|