• Clinical science

Cellular changes and adaptive responses

Abstract

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
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 morphological features of malignant cells → Resemblance to normal cells of a particular tissue where tumor cell originated from is lost.
  • Malignant transformation
Metaplasia
Dysplasia

Proliferation

  • Rapid division and increase in the number of cells
Regeneration

Causes of cell damage

  • Ischemic cell injury: Injury due to a lack of oxygen
    • Atherosclerosis
    • Decreased venous drainage (see ischemia 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., SLE, RA)
  • Genetic defects: misdirect cell metabolism (e.g., cystic fibrosis (CFTR gene), hemophilia A (Xq28 gene), α1-antitrypsin deficiency)
  • Damage induced by medical therapy and chemicals
  • Biological 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
  • Watershed areas
    • Splenic flexure → confluence of blood supply between the SMA and IMA
    • Rectum → confluence of blood supply between the superior rectal artery (branch of the IMA) and the middle and inferior rectal artery

References:[1]

Overview of cell death

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
  • Large group of cells, tissues, or organs
  • Cell swelling, cell blebbing, cell organelle destruction, nuclear changes → cell bursts → inflammation → degradation of the necrotic tissue by leukocytes → organization of granulation tissue

Apoptosis

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

Coagulative necrosis Liquefactive necrosis Fibrinoid necrosis Caseous necrosis Fat necrosis Gangrenous necrosis
Definition
  • A type of necrosis caused by tissue ischemia that occurs in most tissues except the brain
  • A type of necrosis with liquefaction/softening of the affected tissue
  • A type of necrosis characterized by granular debris that results from macrophages walling off a pathogen
  • A type of necrosis in which adipose cells die off prematurely
Pathophysiology
  • Release of hydrolytic enzymes from neutrophilic lysosomes that digest the affected tissue
  • Especially occurs in damaged tissue that contains fat, such as the brain and pancreas
Microscopic appearance
  • Preserved, anuclear, eosinophilic cellular architecture.
  • H&E staining: eosinophilia
  • Macrophages and cellular debris (early) followed by cystic spaces or cavitations (late)
  • In bacterial infections → cellular debris and neutrophils
  • Vessel wall damage with fragments of embedded cellular debris, serum, and fibrin
  • Necrotic areas stain intense red
  • Cellular debris in a granular pattern, epitheloid cells and multinucleated giant cells that form granulomas
  • Adipocytes with no nuclei
  • Saponification: dark blue appearance on H&E staining
Example
  • Myocardial, splenic, hepatic, and renal infarction
  • Gangrene
  • Organ damage caused by acidic solutions
  • Bacterial abscesses (purulent infection)
  • Stroke
  • Pancreatitis
  • Organ damage caused by alkaline solutions

Cellular inclusions

Steatosis

Calcification

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

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. 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.
  • Barone J, Castro MA. Kaplan USMLE Step 1 Lecture Notes 2016. New York, NY, USA: Kaplan Medical; 2016.
  • Goljan EF. Rapid Review Pathology. Philadelphia, PA: Elsevier Saunders; 2018.
last updated 12/03/2018
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