- Reversible changes in number, size, phenotype, or cell function in response to physiologic and pathologic changes in the environment
- Allows cell survival and continued cellular function in an altered steady state
- Results from:
- Increased demand
- Changes in vascular supply, nutrients, or stimulation
- Chronic irritation
- Cells increase in size
- No additional new cells
- ↑ in cellular size → ↑ in size of affected organ
- Can occur along with hyperplasia
- Triggered by:
- Hormonal signaling
- Functional demand
- Physiologic hypertrophy
- Pathologic hypertrophy
- Due to:
- Increased functional demand
- Hormonal stimulation and effect of growth factors
- Clinical correlation:
- Uterine growth in pregnancy
- Skeletal muscle growth after exercise
- Due to increased workload
- Clinical correlation: left ventricular hypertrophy
- Hypertrophy of the wall of the left ventricle
- Occurs in hypertension
- Persistently increased burden → degradation and death of myocytes → cardiac failure
- Increase in cellular protein production resulting from:
- Action of growth factors
- Switch in gene expression
- Enlargement of cells or organs has a limit.
- Regressive changes or cellular death occur when this limit is reached and/or stress is not relieved.
- Cells increase in number in response to a stimulus.
- Can occur simultaneously with hypertrophy
- Occurs only if cells are capable of dividing (cardiac myocytes and neurons in the brain do not undergo hyperplasia)
- ↑ in cellular number → ↑ in size of affected organ
- Physiologic hyperplasia
- Pathologic hyperplasia
- Results from a normal stressor
- Brought on by an increase in hormones and growth factors to enhance functional capacity of the organ
- Hormonal hyperplasia:
- Clinical correlation: glandular epithelium of mammary glands in puberty and pregnancy
- Compensatory hyperplasia:
- Results from damage or resection
- Clinical correlation:
- Restoration of a part of the liver after it has been resected
- Bone marrow hyperplasia in response to acute bleeding
- Partial nephrectomy leads to hyperplasia of the remaining kidney.
- Results from excessive or inappropriate stimulation of hormones or growth factors
- Clinical correlation:
- Prolonged estrogen exposure → endometrial hyperplasia → leading to endometrial bleeding
- Androgens → benign prostatic hyperplasia → bladder outlet obstruction
- Papillomavirus → epithelial hyperplasia → warts and mucosal lesions
- Results from stimulation by growth factors → mature cells proliferate or new cells form from tissue stem cells
- Hyperplasia can stop once the stimulus is removed.
- Unrestricted stimulation → persistent proliferation and increased likelihood of genetic aberrations → increased risk of cancer
- Decrease in size and number of cells, resulting in reduced metabolic activity
- If a sufficient number of cells undergo this process, the whole organ becomes atrophic.
- 2 types of atrophy:
- Results from a normal stimulus
- Clinical correlation:
- Uterine involution: reduction of the size of the uterus after giving birth
- Thyroglossal duct and notochord atrophy during embryonic development
- Can be localized or generalized
- Causes and clinical correlation:
- Loss of workload or disuse atrophy: bedridden patients → prolonged disuse → skeletal muscle fibers decrease in number and size
- Loss of innervation or denervation atrophy: spinal muscular atrophy (SMA), degeneration of the anterior horn of the spinal cord from a defect in the survival motor neuron gene → damaged nerve → skeletal muscle atrophy
- Decrease in blood supply: atherosclerosis → chronic ischemia → aging brain or senile atrophy → cognitive decline
- Lack of nutrition: protein-calorie malnutrition → skeletal muscle proteins are utilized as a source of energy → muscle wasting
- Loss of endocrine stimulation: menopause → loss of estrogen → vaginal atrophy
- Pressure: tumor compresses adjacent tissue → pressure disrupts cells and compromises the blood supply → atrophy of the surrounding tissues
- Note: Hypoplasia is a condition of smaller-than-normal organ or tissue resulting from an abnormal or incomplete development. The tissue involved was never normal in size.
- Characterized by a decrease in protein synthesis and an increase in protein degradation
- Ubiquitin-proteasome pathway:
- Ubiquitin ligases are activated, resulting in attachment of ubiquitin to cellular proteins.
- These proteins become targets for degradation.
- Atrophy is also accompanied by autophagy:
- Self-degradative process in which a cell eats its contents
- Marked by the presence of autophagic vacuoles: contain lysosome-degraded proteins, pathogens, and cellular organelles
- Some cell debris resists autophagy, persisting as residual bodies
- Lipofuscin granules:
- An example of residual bodies, seen in cells as yellow-brown pigment (“wear-and-tear” pigment)
- When increased in a tissue, causes brownish discoloration (brown atrophy)
- If atrophy persistently reduces vascular supply:
- Irreversible cell injury occurs.
- Cells die by apoptosis, a regulated mechanism of cell death, eliminating irreparably damaged cells.
- Differentiated cell types are reversibly changed into another cell type.
- Brought about by chronic irritation
- A cell type is replaced by another type that can better withstand or tolerate the adverse environment that triggered the change.
- Epithelium appears normal but is not in the normal location.
- Reduced function
- Potential malignant transformation of the tissue (when there is a persistence of triggering conditions)
- Generally not a normative cellular adaptive process but can be found with metaplastic epithelia
- Characterized by a disordered pattern of growth, with varying size and shape of the cell and nucleus
- Represents a pre-malignant change
- Respiratory tract and smoking:
- Normal ciliated columnar epithelial cells replaced by stratified squamous epithelial cells
- Squamous epithelial cells: Durable but protective mechanisms (ciliary action and mucus secretion) are lost.
- Barrett’s esophagus: esophageal squamous epithelial cells replaced by intestinal columnar cells due to acid reflux
- Reprogramming of local tissue stem cells: Affected cells are driven by external stimuli toward a specific differentiation pathway.
- The affected organ or tissue is colonized by differentiated cell populations from adjacent sites.
- Left ventricular hypertrophy and heart failure: characterized by hypertrophy of the wall of the left ventricle. The condition is eventually complicated by a reduction in systolic function and/or diastolic dysfunction, leading to heart failure. Left ventricular hypertrophy regression can be achieved with control of blood pressure, weight loss, and medications.
- Endometrial hyperplasia and endometrial cancer: the abnormal proliferation of endometrial glands relative to the stroma, resulting from prolonged estrogenic stimulation. Patients present with abnormal uterine bleeding. Atypical hyperplasia, composed of proliferating glands with nuclear atypia, is associated with an increased risk of endometrial carcinoma.
- Brain atrophy and dementia: Clinical stroke (ischemia or hemorrhage) or cerebral small vessel disease and degenerative processes lead to atrophy of the cerebral structures, from which cognitive and behavioral impairment can develop. Vascular dementia evolves from reduced cerebrovascular supply. Neuroimaging shows infarcts and accelerated brain atrophy. Imaging of Alzheimer’s disease, a neurodegenerative disorder, shows focal or generalized brain atrophy.
- Barrett’s esophagus and esophageal adenocarcinoma: Barrett’s esophagus develops when metaplastic changes occur in the esophagus in order to protect itself from gastric acid reflux. The condition is 1 of the major risk factors for esophageal cancer. Chronic gastroesophageal reflux disease (GERD) predisposes to dysplasia, or disordered growth and architectural disarray of epithelial cells. Dysplastic changes predispose to the development of adenocarcinoma.
- Glick, D., Barth, S., MacLeod, K. (2010) Autophagy: cellular and molecular mechanisms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990190/
- Kemp W.L., & Burns D.K., & Brown T.G. (Eds.) (2008). Cellular pathology. Pathology: The Big Picture. McGraw-Hill.
- McCullough, P., Bakris, G., Forman, J. (2019) Clinical implications and treatment of left ventricular hypertrophy in hypertension. UpToDate. Retrieved 17 Oct 2020, from https://www.uptodate.com/contents/clinical-implications-and-treatment-of-left-ventricular-hypertrophy-in-hypertension
- Oakes, S. (2020) Cell injury, cell death and adaptation in Kumar, V., Abbas, A., Aster, J. & Robbins, S. Robbins and Cotran Pathologic Basis of Disease (10th Ed., pp. 33–65). Elsevier, Inc.