Outline of Lecture
Atrophy & Metaplasia
↓ cell size by ↓ cell substance by protein degradation, digestion & endocytosis.
Physiologic atrophy in normal development
Notochord & Thyroglossal ducts.
Uterus after parturition.
tonsils in adolescence
thymus in early childhood
Loss of endocrine stimulation
Mechanism of atrophy
↓protein synthesis & ↑ protein degradation.
Activation of ubiquitin ligases attach ubiquitin to cellular protein & target these proteins for degradation in proteasomes.
↑ autophagy ↑ autophagic vacuoles ↑ residual bodies (lipofuscin).
Atrophy is the partial or complete wasting away of a part of the body.
Causes of atrophy include mutations (which can destroy the gene to build up the organ),
loss of hormonal support,
loss of nerve supply to the target organ,
disuse or lack of exercise or disease intrinsic to the tissue itself.
Atrophy is the general physiological process of reabsorption and breakdown of tissues, involving apoptosis on a cellular level.
When it occurs as a result of disease it is termed pathological atrophy,
although it can be a part of normal body development and homeostasis as well.
Disuse atrophy of muscles and bones, with loss of mass and strength, can occur after prolonged immobility, such as extended bedrest, or having a body part in a cast
(living in darkness for the eye, reversible with exercise unless severe.
diseases and conditions which cause atrophy of muscle mass. “cachexia“, cancer and AIDS which is notable for the severe muscle atrophy congestive heart failure and liver disease. skeletal muscle atrophy.
Aging there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called “sarcopenia“, and may be distinct from atrophy in its pathophysiology. it may be induced by a combination of a gradual failure in the “satellite cells” which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival
Motor neuron conditions ,atrophying nerve diseases include
CMT (Charcot Marie Tooth syndrome)
Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease),
atrophying muscle diseases include
Changes in Na+ channel isoform expression and
spontaneous activity in muscle called fibrillation can also result in muscle atrophy.
atrophy during prolonged use of exogenous glucocorticoids like prednisone.
can occur with prolonged estrogen reduction, as with anorexia nervosa or menopause.
occurs with prolonged use of enough exogenous sex steroid (either androgen or estrogen) by reduction in gonadotropin secretion.
In post-menopausal women, the walls of the vagina become thinner (Atrophic vaginitis). The mechanism for the age-related condition is not yet clear, though there are theories that the effect is caused by decreases in estrogen levels
Reversible ∆ where one differentiated cell type replaced by another type.
Columnar → Squamous (respiratory)
Squamous →Columnar (barrett esophagus).
Adaptation a reversible change where one adult/mature cell type replaced by another type more suited to new environment.
mesenchymal →fracture bone
Results in loss of some function.
Persistent stimulation → dysplasia →carcinoma
Metaplasia – cell type conversion Metaplasia (Greek: “change in form”) is the reversible replacement of one differentiated cell type with another mature differentiated cell type. not directly considered carcinogenic.
It is also contrasted with heteroplasia, which is the abnormal growth of cytologic and histologic elements without a stimulus.
gastro–esophageal junction with pancreatic acinar metaplasia. The esophageal mucosa (stratified squamous epithelium) is seen on the right. The gastric mucosa (simple columnar epithelium) is seen on the left. The metaplastic epithelial is at the junction (center of image) and has an eosinophilic cytoplasm
Endocervical squamous metaplasia
Mesenchymal Stem cell Blood vessel
Branching / Lumen
Disordered arrangement of cells
Caused by persistent injury / irritation
Squamous dysplasia bronchial