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Cellular Adaptation
- Cellular adaptation is an alteration that enables the cell to maintain a steady state despite adverse conditions.
- Atrophy is a decrease in cellular size caused by aging, disuse, or lack of blood supply, hormonal stimulation, or neural stimulation. The amounts of endoplasmic reticulum, mitochondria, and microfilaments decrease.
- Hypertrophy is an increase in the size of cells caused by increased work demands or hormonal stimulation. The amounts of protein in the plasma membrane, endoplasmic reticulum, microfilaments, and mitochondria increase.
- Hyperplasia is an increase in the number of cells caused by an increased rate of cellular division. Normal hyperplasia is stimulated by hormones of the need to replace lost tissues.
- Dysplasia, or atypical hyperplasia, is an abnormal change in the size, shape, and organization of mature tissue cells.
- Metaplasia is the reversible replacement of one mature cell type by another less mature cell type.
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Cellular Injury
- Cellular injury occurs if the cell is unable to maintain homeostasis. Injured cells may recover (reversible injury) or die (irreversible injury). Injury is caused by lack of oxygen (hypoxia), free radicals, caustic or toxic chemicals, infectious agents, inflammatory and immune responses, genetic factors, insufficient nutrients, or physical trauma from many cases.
- Four biochemical themes are important to cell injury: (a) ATP depletion, (b) oxygen and oxygen-derived free radicals, (c) intracellular calcium and loss of calcium steady state, and (d) defects in membrane permeability.
- The sequence of events leading to cell death is commonly decreased ATP production, failure of active-transport mechanisms (the sodium-potassium pump), cellular swelling, detachment of ribosomes from the endoplasmic reticulum, cessation of protein synthesis, mitochondrial swelling as a result of calcium accumulation, vacuolation, leakage of digestive enzymes from lysosomes, autodigestion of intracellular structures, lysis of the plasma membrane, and death.
- The initial insult in hypoxic injury is usually ischemia (the cessation of blood flow into vessels that supply the cell with oxygen and nutrients).
- Free radicals cause cellular injury because they have an unpaired electron that makes the molecule unstable. To stabilize itself, the molecule gives up an electron to another molecule or steals one. Therefore it forms injurious chemical bonds with proteins, lipids, and carbohydrates-key molecules in membranes and nucleic acids.
- The damaging effects of free radicals, especially activated oxygen species (O2-, OH-, H2O2), include (a) lipid peroxidation, (b) alteration of ion pumps and transport mechanisms, (c) fragmentation of DNA and (d) damage to mitochondria-releasing calcium into the cytosol.
- Restoration of oxygen, however, can cause additional injury called reperfusion injury.
- The initial insult in chemical injury is damage or destruction of the plasma membrane; Examples of chemical agents that cause cellular injury are carbon tetrachloride, lead, carbon monoxide, and ethyl alcohol.
- Unintentional and intentional injuries are an important health problem in the United States. Death as a result of these injuries is more common for men than women and higher among blacks than whites and other racial groups.
- Injuries by blunt force are the result of the application of mechanical energy to the body, resulting in tearing, shearing, or crushing of tissues. The most common types of blunt-force injuries include motor vehicle accidents and falls.
- A contusion is bleeding into the skin or underlying tissues as a consequence of a blow. A collection of blood in soft tissues or an enclosed space may be referred to as a hematoma.
- An abrasion (scrape) results from removal of the superficial layers of the skin caused by friction between the skin and injuring object. Abrasions and contusions may have a patterned appearance that mirrors the shape and features of the injuring object.
- Lacerations are a tear or rip resulting when the tensile strength of the skin or tissue is exceeded.
- An incised wound is a cut that is longer than it is deep. A stab wound is a penetrating sharp-force injury that is deeper than it is long.
- Gunshot wounds may be either penetrating (bullet retained in the body) or perforating (bullet exists). The most important factors determining the appearance of a gunshot injury are whether it is an entrance or an exit wound and the range of fire.
- Asphyxial injuries are caused by a failure of cells to receive or utilize oxygen. These injuries can be grouped into four general categories: suffocation, strangulation, chemical, and drowning.
- Activation of inflammation and immunity, which occurs after cellular injury or infection, involves powerful biochemicals and proteins capable of damaging normal (uninjured and uninfected) cells.
- Genetic disorders injure cells by altering the nucleus and the plasma membrane’s structure, shape, receptors, or transport mechanisms.
- Deprivation of essential nutrients (proteins, carbohydrates, lipids, vitamins) can cause cellular injury by altering cellular structure and function, particularly of transport mechanisms, chromosomes, the nucleus, and DNA.
- Injurious physical agents include temperature extremes, changes in atmospheric pressure, ionizing radiation, illumination, mechanical stress (e.g., repetitive body movements), and noise.
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Manifestations of Cellular Injury
- Cellular manifestations of cellular injury include accumulations of water, lipids, carbohydrates, glycogen, proteins, pigments, hemosiderin, bilirubin, calcium, and urate.
- Accumulations harm cells be “crowding” the organelles and by causing excessive (and sometimes harmful) metabolites to be produced during their catabolism. The metabolites are released into the cytoplasm or expelled into the extracellular matrix.
- Cellular swelling, the accumulation of excessive water in the cell, is caused by the failure of transport mechanisms and is a sign of many types of cellular injury. Oncosis is a type of cellular death resulting from cellular swelling.
- Accumulations of organic substances-lipids, carbohydrates, glycogen, proteins, pigments-are caused by disorders in which (a) cellular uptake of the substance exceeds the cell’s capacity to catabolized (digest) or uses it or (b) cellular anabolism (synthesis) of the substance exceeds the cell’s capacity to use or secrete it.
- Dystrophic calcification (accumulation of calcium salts) is always a sign of pathologic change because it occurs only in injured or dead cells. Metastatic calcification, however, can occur in uninjured cells in individuals with hypercalcemia.
- Disturbances in urate metabolism can result in hyperuricemia and deposition of sodium urate crystals in tissue-leading to a painful disorder called gout.
- Systemic manifestations of cellular injury include fever, leukocytosis, increased heart rate, pain, and serum elevations of enzymes in the plasma.
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Cellular Death
- Cellular death is manifested as cellular dissolution, or necrosis. Necrosis is the sum of the changes after local cell death and includes the process of autolysis, or cellular self-destruction.
- There are four major types of necroses: coagulative, liquefactive, caseous, and fat necroses. Different types of necroses occur in different tissues.
- Structural signs that indicate irreversible injury
- and progression to necrosis are the dense clumping and disruption of genetic
- material and the disruption of the plasma and organelle membranes.
- Apoptosis, a distinct type of sublethal injury, is a process of selective cellular self-destruction that occurs in both normal and pathologic tissue changes.
- Gangrenous necrosis, or gangrene, is tissue necrosis caused by hypoxia and the subsequent bacterial invasion.
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Aging & Altered Cellular and Tissue Biology
- It is difficult to determine the physiologic (normal) from the pathologic changes of aging.
- Humans have an inherent maximal life span (80 to 100 years) that is dictated by currently unknown intrinsic mechanisms.
- Although the maximal life span has not changed significantly over time, the average life span, or life expectancy, has increased. Life expectancy for men is about 75 years, and for women it is 80 years.
- The physiologic mechanisms of aging apparently are associated with (a) cellular changes produced by genetic and environmental-lifestyle factors, (b) changes in cellular regulatory or control mechanisms, and (c) degenerative extracellular and vascular alterations.
- Frailty is imprecisely defined as a wasting syndrome of aging leaving a person vulnerable to falls, functional decline, disease, and death.
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Somatic Death
- Somatic death is death of the entire organism. Postmortem change is diffuse and does not involve the inflammatory response.
- Manifestations of somatic death include cessation of respiration and circulation, gradual lowering of body temperature, pupil dilation, loss of elasticity and transparency in the skin, muscle stiffening (rigor mortis) and skin discoloration (livor mortis). Signs of putrefaction are obvious about 24 to 48 hours after death.
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