Mechanism of Injury

Living cells and tissue adjust to a changing environment (balanced state = homeostasis).
Stress in the environment induces adaptive mechanisms, and failure of these leads to cell injury or death, which can be at the organ or cellular level.
Changes can also happen over time with aging (not really a disease process).

Macroscopic: at the organ level, hypertrophy, atrophy, dysplasia, pigmentation, calcification (like in severe atherosclerosis), fatty change (liver)
  * Hypertrophy: increase in size
  * Atrophy: decrease in size
  * Dysplasia: Change in how cells look

Microscopic: at the cellular level, inclusions (could be iron, fat, lipofuscin (aging)), pigmentation, multinucleation, apoptosis, necrosis
* Hyaline inclusions in the liver = Mallory bodies from alcohol

Increased demand or chronic stimulation → Hypertrophy, hyperplasia (muscle growth)
* Hypertrophy: cells increase in size, and organs increase in size (^^dividing and non-dividing cells^^)
* Hyperplasia: increase in the number of cells (^^dividing cells only^^)
Decreased demand or lack of stimulation → atrophy
* Atrophy: Shrinkage in cell size (or organ)
Chronic injury → Metaplasia
* Metaplasia: cells change from one cell type to another

Physiological Hypertrophy: Uterus during pregnancy (both organ and cells) and muscle growth
Pathological Hypertrophy: Myocytes in the heart become over-stressed due to prolonged hypertension or valve disease

Prostate Hyperplasia → Benign prostatic hyperplasia (BPH) (aka nodular hyperplasia), due to testosterone being converted into DHT which is more potent.
* Men have trouble voiding the bladder.

Physiological Atrophy: shrinkage of the uterus after pregnancy, occurs due to loss of hormonal stimulation from the placenta and developmental gene regulation.
Pathological Atrophy: Muscle atrophy after a fracture, brain with Alzheimer’s
* (due to inactivity, lack of innervation, loss of perfusion, lack of nutrition, loss of hormonal stimulation, aging, or pressure)

$Metaplasia INCREASES the risk of cancer$
Squamous Metaplasia: Occurs in the upper airways usually in smokers, columnar epithelium switches to squamous epithelium due to stress.
Intestinal Metaplasia: AKA gastro-esophageal junction or Barrett’s esophagus, squamous epithelium switches to glandular columnar epithelium due to GERD.

Murder weapon: oxygen deprivation, physical injury (heat/cold/electric), chemical, infectious agent, immune system (friendly fire), genetic defects, or nutritional deficiencies.
Cells can either die by necrosis which causes inflammation or apoptosis which is silent.
* This can be determined by DNA laddering

Extrinsic: death receptor-mediated (ligand binds the receptor)
Intrinsic: Mitochondrial-mediated
Endoplasmic Reticulum Stress Pathway: Mediated by too little or too much Calcium

Necrosis is enzymatic digestion and leakage of cellular components; violent tissue death
Myocardial Infarct: ischemic necrosis of the myocardium
Coagulation Necrosis: “dry necrosis” where the basic cell outline is maintained, Nuclei lost, cytoplasm, eosinophils, hypoxic cell death
Liquefactive Necrosis: “liquid/wet necrosis” where tissue dissolves, every structure is lost, and NO cells are visible (infections like TB or ^^ANYTHING in the brain^^)

Gangrene (Gangrenous Necrosis): dry or wet necrosis, often after a loss of blood supply
* (diabetic foot, peripheral artery disease, frostbite (dry))
Caseous Necrosis: in TB the lung cavity is filled with “cheesy” white-yellow material
Fat Necrosis: Fat destruction of the Mesentery (tissue-fat sheet in the belly)
* frequently occurs after pancreatitis
* Lipase or other digestive enzymes meet lipids and calcium and complex to form chalky “soap” deposits.