Altered Cellular and Tissue Biology

Adaption

reversible response involving structural or functional modifications to accommodate both physiologic (normal) demands and pathologic (adverse) conditions

Common sources of cell stress

structural damage, neoplasia, fluid/solute accumulations, genetic influences, aging

Sublethal

injury that is reversible

Lethal

injury that is irreversible

Atrophy

decrease in cell size usually happens in skeletal muscle, heart muscle, secondary sex organs, and the brain

Physiologic atrophy

normal event, not using something (muscle)

Pathologic atrophy

occurs because of decreases in workload, pressure, use, blood supply, nutrition, hormonal stimulation, or neural stimulation (Alzheimers Disease)

Disuse atrophy

due to something not being used, limb in cast, bed rest, or other immobilization

Autophagy

eating of self, cytoplasmic vesicles engulf cytoplasm and organelles, recycling factory

Lipofuscin

yellow-brown pigmented granules composed of lipid-containing residue that persists after lysosomal destruction

Hypertrophy

compensatory increase in the size of cells that occurs in response to mechanical load or stress and results in increased size of the affected organ (heart and kidneys are prone)

Physiologic hypertrophy

results from increased demand, stimulation by hormones, and growth factors (cardiac: increase in chamber size, thickness, left ventricle)

Pathologic hypertrophy

results from chronic hemodynamic overload, such as from hypertension or heart valve dysfunction (thickening of the left ventricle)

Hyperplasia

increase in the number of cells resulting from an increased rate of cellular division (response to when the damage is severe or prolonged or when it results in cell death)

Compensatory hyperplasia

adaptive mechanism that enables organs to regenerate (example is a callus)

Hormonal hyperplasia

occurs in organs that respond to endocrine hormonal stimulation

Pathologic hormonal hyperplasia

abnormal proliferation of normal cells, usually in response to excessive hormonal stimulation or to the action of growth factors on target cells

Dysplasia (atypical hyperplasia)

abnormal changes in the size, shape, and organization of mature cells ( can be low or high grade)

Metaplasia

reversible replacement of one mature cell type with another cell type, frequently one less differentiated

Mesenchyme

type of loosely organized embryonic connective tissue of undifferentiated cells

Cytokines

broad category of small proteins for cell signaling growth factor

Hypoxia

lack of sufficient oxygen within cells, us the single most common cause of cell injury

Ischemia

decreased supply of blood and therefore oxygen (most common hypoxia)

Common themes in cell injury and cell death

ATP depletion, reactive oxygen species, Ca2+ entry, mitochondrial damage, membrane damage, membrane damage, protein misfolding, DNA damage

Anoxia

total lack of oxygen caused by an acute obstruction or a thrombus

Myocardial infarction

heart attack if the blood supply is not restored, can be a result of acute obstruction in coronary artery

Vacuolation

formation of vacuoles

Ischemia-reperfusion injury

mechanisms for injury include oxidative stress, increased intracellular calcium concentration, inflammation, and complement activation

Oxidative stress

casued by endogenous and exogenous agents, or both, increase in different reactive species, depletion of antioxidant defense (results in detremental oxidation of macromolecules)

Reactive oxygen species (ROS)

oxygen-containing reactive molecules produced from utilization of molecular oxygen, mostly by mitochondria

Free radical

an electrically uncharged atom that has an unpaired electron

Generation of free radicals

1. Reduction-oxidative reactions

2. absorption of extreme energy sources

3. enzymatic metabolism of exogenous chemicals or drugs

4. transition metals (iron and copper) - create hydroxyl radicals

5. Nitric oxide (NO)

Free radical damages

1. lipid peroxidation

2. protein alteration

3. DNA damage

4. mitochondrial effects

Antioxidants

molecules that inhibit the oxidation of other molecules, preventing the formation of free radicals

Endogenous antioxidants

produced by body, superoxide dismutase, alpha lipoic acid, catalase, coenzyme Q10, and glutathione peroxidase

Exogenous antioxidants

originate outside the body, typically from dietary sources

Xenobiotics

compounds and chemicals that have toxic, mutagenic, or carcinogenic properties

Biotransformation

the process whereby enzymatic reactions convert one chemical into a less toxic or nontoxic compound

Ambient particulate matter

contains particles that are less than or equal to 2.5 micrometers in aerodynamic matter, world’s leading environmental health risk factor

Ozone (O3)

spacial form of oxygen found in the stratosphere, can be created by chemical reactions at ground level and have caused deaths from chronic lung disease

Heavy Metals

most common heavy metals associated with harmful effects in humans include lead, mercury, arsenic, and cadmium

Asphyxiation

lack of oxygen four categories: suffocation, strangulation, chemical asphyxiants, and drowning

Suffocation

process of dying because of a lack of oxygen

Choking asphyxiation

occurs when there is an obstruction of pulmonary airways

Strangulation

caused by compression of the blood vessels and air passages resulting from external pressure on the neck

Cellular accumulations (infiltrations)

1. normal cellular substances: excess water, proteins, lipids, and carbohydrates

2. abnormal substances: endogenous substances (products of abnormal metabolism and synthesis) and exogenous substances (infectious agents or minerals)

Cellular swelling

most common degenerative change, results from a shift of extracellular water into the cells

Oncosis or vacuolar degeneration

cytoplasmic swelling due to progressive vacuolation

Steatosis

fatty changes occur, most common site of intracellular lipid accumulation is the liver

Glycogen

storage form of glucose, storage diseases of this have effects on growth and development, and negatively affect a variety of organ and body system functions

Protein accumulation

protein metabolism results in the release if lysosomal enzymes can damage cellular organelles, excessive amounts of protein in the cytoplasm crowd cell organelles disrupting function and communication

Biochemical events cause cell injury and cell death

1. ATP depletion resulting in mitochondrial damage

2. accumulation of oxygen and reactive oxygen species, resulting in membrane damage

3. increased intracellular calcium concentration and loss of calcium steady state

4. mitochondrial damage, resulting in loss of membrane potential and activation of cell death

5. membrane damage

6. protein folding defects

Alcohol cell injury

altering nutritional status, metabolism of acetaldehyde, and affecting the liver, CNS, and other body tissues

Genetic disorders

result in cell injury by altering the nucleus and the plasma membrane (structure, shape, receptor, or transport mechanisms)

Deprivation and excessive consumption

proteins, carbohydrates, lipids, vitamins, can result in cell injury by altering cellular structure and function

Environmental factors

temp extremes, changes in atmospheric pressure, ionizing radiation, illumination, mechanical stresses, and excessive noise can cause cell injury

Accumulations secondary to:

1. normal substance is insufficiently removed due to altered configuration or transport

2. an abnormal substance accumulates, often secondary to a gene mutation

3. an endogenous substance is inadequately catabolized

4. an inhaled or ingested harmful exogenous substance accumulates or is produced secondary to an infection

Dystrophic calcification

the accumulation of calcium salts in injured or dead cells and is a sign of pathologic change

Systemic manifestation of cell injury

fever, leukocytosis, increased heart rate, pain, and serum elevations of plasma enzymes

Necrosis

pathological cell death, caused by severe injury, and involves loss of plasma membrane integrity, swelling, and dysfunction (autolysis, a process of cellular self-digestion)

Karyolysis

enzymatic hydrolysis of nuclear chromatin

Pyknosis

a process whereby the nucleus shrinks into a small dense mass of genetic material occurs

Karyorrhexis

fragmentation of the nucleus into small particles or “nuclear dust”

Coagulative necrosis

protein denaturation when albumin is transformed from gelatinous, loss of cell structure

Liquefactive necrosis

results from ischemic injury to neurons and glial cells in the brain, digestion of cells

Caseous necrosis

a combination of coagulative and liquefactive necrosis, seen in tuberculosis, dead cells disintegrate (resembles clumped cheese)

Fatty necrosis

cellular dissolution caused by lipases (enzyme in breast, abdominal structures, and pancreas) occurs in fat tissue

Gangrene

tissue death due to lack of blood flow and infection by anaerobic bacteria (diabetic foot ulcers)

Gas gangrene

type of wet gangrene caused by tissue infection with Clostudium ssp.

Apoptosis

programmed cell death, cells undergo controlled deconstruction to eliminate damaged cells without causing inflammation, critical in processes including development, immune responses, and eliminating cancerous cells

Caspases

family of aspartic acid-specific enzymes that trigger proteolytic activity in response to signals

Aging and autophagy

the “garbage-collecting” and recycling functions that characterize autophagy become lass efficient and less discriminating in aging individuals

Aging Process

aging leads to reduced cellular repair mechanisms, DNA damage, and cellular function decline

Sarcopenia

loss of muscle mass associated with aging

Frailty Syndrome

characterized by weakness, fatigue, and susceptibility to disease and injury in older adults

Somatic Death

refers to death of the entire organism and postmortem changes that occur in a predictable sequence

Frailty mechanisms

inflammation, loss of stem cell regeneration, DNA damage, metabolic decline, hormonal alterations, epigenetics factors, and loos of protein regulation