Cell Injury Robert Low MD PhD
Cell and tissue injury produce human disease Injury-acute vs chronic • sites within cells that are easily injured • reversibility of injury and complete recover • adaptation to chronic injury • cell death-necrosis vs apoptosis • Hypoxic injury-starving cells/tissues for oxygen; problems of too much oxygen and cell damage from oxygen radicals
#1 • Human disease occurs because of injury to cells/tissue
Cell Injury– Damage or alteration of one or more cellular components Many types of injury we incur are tissue specific because of anatomic relationships and the tissue tropism of chemical and infectious agents. Cell injury perturbs cell physiology; the cell does not function at full capacity.
Basic Types of Tissues • Epithelium • Muscle (skeletal, smooth, cardiac) • Nerve (CNS, PNS) • Connective (bone, cartilage, soft tissue, adventitia, ligaments, blood and lymph, etc)
#2 • Most human disease results from injury to Epithelium
Epithelium arises from each of three germ layers • Cells cover external surfaces (skin); line internal closed cavities, secretory glands and tubes- -GI, respiratory, GU tracts- -that communicate with external surfaces • Also includes liver, exocrine pancreas, parotid glands, thyroid, parathyroid, epithelium of kidney • Also: vascular endothelium, mesothelium
#3 • Injury to one tissue usually affects the adjacent or underlying tissue as well
Cell Injury Produces: • Signs- abnormal physical findings • Symptoms- complaints experienced by the patient
Cell Injury Produces: (cont) • Morphologic change- A visual change in the cell shape or appearance, seen when cells are stained and viewed by light microscopy; or examined by E.M. in the injured tissue; or seen “grossly” with the naked eye.
Outcomes from cell injury depend upon: • Type of injury • Severity of the injury • Duration of the damage • Type of cell being injured- Some cell types sustain injury better than others; some tissues (e.g. liver) have a capacity to regenerate.
Cell Injury: Vulnerable Sites • Cell membranes • Mitochondria • Endoplasmic reticulum • Nucleus
Cell Membrane- why so easily injured • Membrane faces the external environment: sustains “trauma”, extracellular oxidants, proteases, etc. • Requires a constant supply of ATP for normal function (ion pumps). • Lipid molecules in the membrane are easily oxidized and support and oxidative chain reaction called lipid peroxidation.
Consequences of Injury • No long term effects- - the cell damage is repaired, the effects of the injury are reversible. • The cell ”adapts” to the damaging stimulus. • The cell dies, undergoing necrosis. The damage is irreversible.
Reversible Cell Injury Examples: • Cell swelling – usually accompanies all types of injury. Results from an increase in water permeability. Reverses once membrane function is restored. • Increase in extracellular metabolite because of a biochemical derangement. Ex.: Increase in extracellular glycogen in diabetes.
Reversible Cell Injury (cont) Examples: • Fatty change in liver. Vacuoles of fat accumulate within the liver cell following many types of injury: alcohol intoxication, chronic illness, diabetes mellitus, etc. Due to: An increase in entry of free fatty acids. An increase in synthesis of free fatty acids. A decrease in fatty acid oxidation.
Adaptation- the cell responds successfully to the injurious stimulus Examples: • Hypertrophy- the cell increases in size.Ex.: cardiac myocytes of the left ventricle increase in size from essential hypertension. • Atrophy- the cell decreases in size because of a loss of cell substance.
Causes of Cell Atrophy • Loss of blood supply or innervation • Loss of endocrine factors (ex. TSH) • Decrease in the workload • Aging, chronic illness
Cell Death • Necrosis • Apoptosis
Coagulative Necrosis • Dead cell remains a ghost-like remnant of its former self-classically seen in an MI.