Atrophy

DEFINITIONdecrease in size and weight (or function, clinically) of a tissue/organ due to decrease in size and number of its constituent parenchymal cells

CAUSESLoss/interruption of trophic signals:

Decreased hormonal stimulation of hormone-responsive tissue

Dennervation of muscleThe activities of many cells depend on signals triggered by chemical mediators (e.g., hormonal or neuromuscular transmission), which place functional demands on them. If the source of the signal is removed (e.g., via ablation of an endocrine gland or denervation), cells dependent on that stimulus will atrophy.

If the anterior pituitary is surgically resected or lost to ischemia (e.g., Sheehan syndrome), deficiency of TSH, ACTH and FSH results in atrophy of the thyroid, adrenal cortex and ovaries, respectively.Physiological atrophy of breast and uterus following menopause, when estrogen stimulation is diminished

Skeletal muscle atrophy following lower motor neuron loss in Amyotrophic lateral sclerosis; nerve section as in spinal cord injuries; poliomyelitis

Decreased workload/functional demand-Disuse atrophySkeletal muscle in plaster cast

Decreased blood supplyCerebral atrophy due to atherosclerosis of CACerebral atrophy in Alzheimer's diseaseAtrophy of brain and heart in aging (senile atrophy)Although total cessation of oxygen perfusion results in cell death, partial ischemia is often compatible with cell viability.Atrophic kidney in renal artery atheroscelrosis

Decreased nutritionCalorie deprivation in marasmus/kwarshiokorAs a result of utilization of skeletal muscle proteins as source of energy after other reserves have been depleted.

Increased pressure/compressionAtrophy of renal cortex and medulla in hydronephrosis (increased luminal pressure of backed up urine compresses vessels in medulla and cortex)Compression atrophy of exocrine glands in cystic fibrosis (thick pancreatic duct secretions occlude duct lumens, causing increased luminal back pressure, resulting in atrophy and damage)Enlarging benign tumor/cyst/aneurysm can cause atrophy of surrounding uninvolved tissues.(erosion of spine by tumor in nerve root, erosion of skull by meningioma, erosion of sternum by arch of aorta aneurysm)Decubitis ulcers/pressure ulcers/bed sores (When soft tissues are compressed between bony prominences and contact surfaces, microvascular occlusion with tissue ischemia and hypoxia occurs)Atrophy of hepatocytes in the center of the liver lobule, in congestive heart failure (poor venous return from the liver increases the pressure within hepatic sinusoids)

Pressure exerted causes the blood supply to compromise, resulting in ischemic/hypoxic changes??

Persistent cell injury caused by chronic inflammation associated with bacterial/viral infectionsAtrophy of gastric mucosa, associated with chronic gastritisSmall intestinal villous atrophy accompanying the chronic inflammation of celiac disease

Chronic disease like AIDS/CancerGeneralised atrophy of many tissues; [emaciation and anaemia referred to as cachexia seen in cancer and severely ill patients.](often due to decreased calorie intake and alterations in cytokines and other mediators)

Idiopathic atrophiesMyopathiestesticular atrophy?

MECHANISMS

SHRINKAGE OF CELLS (by reduction in cytosol and number of organelles through Autophagy[formation of autophagic vacuoles-fusion with primary lysosomes=autophagolysosomes->enzymatic degradation]..[lipid peroxidation of cell membranes-undigested stored as residual bodies, e.g. Lipofuscin, brown tissue discoloration/brown atrophy, normal age-related finding)LOSS OF CELLS by PCD/apoptosisPROTEIN CATABOLISM-decreased protein synthesis (wasting syndrome?/catabolic state?) and increased protein degradation (ubiquitin-proteasome pathway)