• Clinical science

Cellular changes and adaptive responses

Summary

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.

Cellular adaptation

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
  • A degeneration of tissue or organ (e.g., due to malnutrition or hereditary disease).
Hypertrophy
  • Increased tissue size via enlargement of cells caused by an increase in organelles, and structural proteins.
Hyperplasia
  • Increased tissue size via an increase in cell numbers
Anaplasia
  • Loss of mature cellular differentiation (no longer have morphological features of mature cells)
  • Malignant transformation
Metaplasia
Dysplasia
  • Disordered growth of epithelium (abnormally frequent mitotic figures, loss of cell orientation, size, and shape)
  • Precancerous: can progress to carcinoma in situ

Proliferation

  • Rapid division and increase in the number of cells
Regeneration

References:[1][2]

Cell injury

Overview

Causes

Ischemia

Organs most susceptible to ischemia
Organ Specific structure Clinical significance
Brain
Heart
Kidney
  • Proximal tubule (straight segment in the medulla)
  • Thick ascending limb (in the medulla)
Liver
  • Region around the central vein (zone III)
  • Centrilobular necrosis (e.g., Budd-Chiari syndrome, shock liver in trauma)
Bowel
  • Ischemic tolerance time, after which irreversible tissue damage begins to take place
    • Skin: 12 h
    • Musculature: 6–8 h
    • Neural tissue: 2–4 h

References:[2]

Reperfusion injury

Reperfusion injury is tissue damage that occurs when blood flow is restored to a previously ischemic environment (typically > 6 h for most tissues).

Overview of cell death

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

Apoptosis vs. necrosis

Characteristics Apoptosis Necrosis
Definition
Pathophysiology
Microscopy
  • Single cell or small group of cells
  • Cell shrinkage
  • Eosinophilic cytoplasm
  • Nuclear changes
  • Cytoplasmic blebs
  • Apoptotic bodies → phagocytized by macrophages

References:[3]

Apoptosis

  • Description: programmed cell death (physiological cell turnover)
  • Causes
  • Characteristics
    • ATP-dependent physiological process
    • Usually affects individual cells and not groups of cells (in contrast to necrosis)
    • No inflammatory response or cellular swelling (in contrast to necrosis)

Signaling cascade

Apoptosis can be initiated via two different pathways: the extrinsic pathway (through external stimuli) or the intrinsic pathway (through internal stimuli).

Histopathological findings

  1. Shrunken and irregularly shaped cells with membrane blebbing
  2. The cell detaches from other cells or the extracellular matrix.
  3. Nuclear changes (pyknosis, karyorrhexis, karyolysis)
  4. Degradation of the cell into apoptotic bodies
  5. Phagocytosis by macrophages
  6. DNA laddering (fragments in multiples of 180 base pairs) is seen on gel electrophoresis

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

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. Some examples include:

Necrosis

Types of necrosis

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 staining: eosinophilia
Liquefactive necrosis
  • A type of necrosis with liquefaction/softening of the affected tissue
  • Release of hydrolytic enzymes from neutrophilic lysosomes that digest the affected tissue
  • Macrophages and cellular debris (early) followed by cystic spaces or cavitations (late)
  • In bacterial infections → cellular debris and neutrophils
Fibrinoid necrosis
  • Vessel wall damage with fragments of embedded cellular debris, serum, and fibrin
  • Necrotic areas stain intense red
Caseous necrosis
  • A type of necrosis characterized by granular debris that results from macrophages walling off a pathogen
Fat necrosis
  • A type of necrosis in which adipose cells die off prematurely
  • Adipocytes with no nuclei
  • Saponification: dark blue appearance on H&E staining
Gangrenous necrosis


Cellular inclusions

Steatosis

Calcification

Can be metastatic (diffuse) or dystrophic (localized)

Metastatic calcification Dystrophic calcification
Description
  • Diffuse calcification of normal tissue
  • Localized calcification of degenerated inflammatory sites or necrotic tissues
Involved tissues
  • Normal tissues of kidney, lung, gastric mucosa, and blood vessels
  • Abnormal necrotic tissues or degenerated inflammatory sites
Etiology

Associated conditions/tissue

Serum calcium findings
  • Usually increased
  • Usually normal

Histology

  • Finely speckled calcium throughout soft tissues

Hyalinization

  • 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.

Intracellular hyaline

Intracellular

hyaline (inclusion bodies)

Morphology Occurrence
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

Extracellular hyaline

  • 1. Barone J, Castro MA. Kaplan USMLE Step 1 Lecture Notes 2016. New York, NY, USA: Kaplan Medical; 2016.
  • 2. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • 3. Goljan EF. Rapid Review Pathology. Philadelphia, PA: Elsevier Saunders; 2018.
  • Guerini D. The Ca2+ pumps and the Na+/Ca2+ exchangers. Biometals. 1998; 11(4): pp. 319–30. pmid: 10191496.
last updated 12/06/2019
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