chapter 3: cellular adaptation, injury, and death

cellular adaptation

cell’s response to escape + protect itself from injury

adaptive changes in cellular adaptation

atrophy, hypertropy, hyperplasia, metaplasia, dysplasia

cellular adaptation vs cellular injury

• cellular adaptation: reversible, and non-lethal change to stress

• cellular injury: happens when stress too severe for cell to handle

causes, mechanisms, reversibility, and outcomes of cellular adaptation

• causes: mild ongoing stress

• mechanism: cell changes its size, number, or type to survive

• reversibility: can reverse; goes back to normal when stress stops

• outcome: cell lives + keeps working

causes, mechanisms, reversibility, and outcomes of cellular injury

• cause: sudden severe stress

• mechanism: cell’s parts + walls get damaged

• reversibility: only if mild; if too bad, can’t be fixed

• outcomes: cell either heals or dies

atrophy

decrease in cell size = results in reduction of tissue or organ size

physiologic atrophy

normal + expected adaptation; occurs due to decreased activity + reduced hormone stimulation, aging changes

• ex: involution of thymus, decrease muscle mass w/ aging, uterine shrinkage after menopause

pathologic atrophy

caused by disease or abnormal conditions; results from decreased workload, blood supply, pressure, poor nutrition, loss of hormonal stimulation, nervous stimulation

• cells adapt by: decreasing protein synthesis, increasing protein synthesis, activating autophagy (self-eating)

• ex: disuse (prolonged bed rest or immobilization), muscle loss from nerve injury

hypertrophy

increase in cell size = results in enlargment of tissue or organ; caused by increased work demand or hormones

physiologic hypertrophy

normal adaptive response

• ex: muscle growth from weight training

pathologic hypertrophy

occurs due to disease or abnormal stress

• ex: left ventricular ___ from hypertension (high BP)

hyperplasia

increase in cell number caused by increased rate of cellular division

physiologic hyperplasia

two common types: compensatory and hormonal

• compensatory: allows organ to regenerate

  • ex: regeneration of liver after partial removal

• hormonal: replaces lost tissue or supports new growth

  • breast gland enlargement during pregnancy resulting form estrogen stimulation

pathologic hyperplasia

results from excessive hormonal stimulation or effects of growth factors on target tissue

• ex: enlargement of prostate in BPH (causes urinary problems)

dysplasia

deranged cellular growth, not true cellular adaptation, rather an atypical hyperplasia

• refers to abnormal changes in size, shape, organization of mature cells

  • not indication of cancer (if treated) + occurs usually in epithelial tissues (cervix, colon, skin)

• ex: cervical ___: abnormal cells on cervix of uterus, often linked to HPV infection

metaplasia

reversible replacement of one mature cell by another less mature one

• ex: barrett esophagus = chronic acid reflux causes normal squamous lining of esophagus to change intestinal-type cells; replacement of normal bronchial columnar ciliated epithelial cells by stratified squamous epithelial cells

cellular injury

damage that occurs when cells exposed to stressful/harmful agents beyond ability to adapt

• reversible injury: cells recover if stress is removed

• irreversible injury: cells die

common causes of cellular injury

• lack of oxygen (hypoxia)

• free radicals

• chemical and infectious agents

• physical and mechanical factors, immunologic reactions, genetic factors, nutritional imbalances, physical trauma

cellular injury leads to death by:

• decreased ATP production (mostly)

• failure of active transport mechanisms (Na+/K+ pump)

• cellular swelling

• detachment of ribosomes from endoplasmic reticulum

• cessation of protein synthesis

• mitochondrial swelling fro calcium accumulation

• leakage of digestive enzymes from lysosomes

• lysis of plasma membrane

ischemia-reperfusion injury (common); cellular injury mechanism

• ischemia phase (low oxygen): cells switch to anaerobic metabolism (atp down), ion pumps fail (cells swell = calcium build up)

• reperfusion phase (blood returns): sudden oxygen influx leads to burst of reactive oxygen species (ROS), oxidative stress radials (ROS) cause membrane damage and mitochondrial calcium overload

• mechanism of injury in: tissue transplantation, ischemic syndromes (myocardial, hepatic, etc)

chemical or toxic injury; cellular injury mechanism

direct toxicity to cell (damage to/destruction of plasma membrane) + reactive free radicals + lipid peroxiation

• ex: lead, carbon monoxide, ethyl alcohol, mercury

  • lead: affects central and peripheral nervous sytems

  • carbon monoxide: directly reduces the oxygen-carrying capacity of blood, and promotes tissue hypoxia

  • ethyl alcohol: results in major nutritional deficiencies, especially folate

  • mercury: affects nervous system, kidneys

free radicals & reactive oxygen species (ROS)—oxidative stress

• increase of different reactive species

• detrimental oxidation of lipids, proteins, and nucleic acids

  • lipids: loss of membrane integrity, increased permeability

  • proteins: enzyme inactivation, protein fragmentation

  • nucleic acids: gene mutations

• mitochondrial effects: dysfunction caused by ROS, inefficient antioxidants

two types of cellular death

necrosis and apoptosis

necrosis

• uncontrolled death of cells and tissues in living organisms + usually caused by injury

• includes inflammatory changes = leads to autolysis

  • after cell death + process of cellular autodigestions (autolysis)

necrosis processes include:

• pyknosis: shrinking of nucleus; nucleus becomes smaller and dark

• karyorrhexis: fragmentation of nucleus; DNA broken into pieces

• karyolysis: nuclear dissolution + chromatin lysis; DNA digested by enzymes, nucleus disappears

types of necrosis

coagulative necrosis, liquefactive necrosis, caseous necrosis, fat necrosis, gangreneous necrosis

coagulative necrosis

cells transformed to gray, firm mass

• protein denaturation resulting from activation of enzymes

• common in kidneys, heart, and adrenal glands

liquefactive necrosis

hydrolytic enzymes form liquid-filled cyst or form pus

• common in neurons and glial cells in brain

caseous necrosis

cells transformed into cheese-looking substance that’s walled off

• tuberculosis pulmonary infection + is combo of coagulative and liquefactive necrosis

fat necrosis

occurs exclusively in adipose tissue

• common in breast, pancreas, other abdominal structures

• action of lipases: break down lipids into fatty acids

gangrenous necrosis

considerable mass of tissue undergoes necrosis; may be classified as: dry, wet, gas gangrene

• dry: tissue dries + shrinks, skin wrinkles + color changes to dark brown + black; caused by severe blood supply loss

• wet: occurs when dead tissue becomes infected by bacteria, leads to rapid tissue breakdown + swelling

• gas gangrene: special type results from infection of tissues by one of several clostridium bacteria

apoptosis

programmed cellular death

• highly selective process eliminates injured + aged cells = controls tissue regeneration

• dysregulated ____, autophagy (also cellular death)

dysregularted apoptosis

excessive/insufficient

• leads to cancer, autoimmune disorders neurodegenerative disease and ischemic injury

autophagy

from greek: “self eating” (auto- = self, -phagy = eating)

• self-destructive: digests its own damaged parts, old organelles, or misfolded proteins, process to clean house + generate energy

• survival mechanism: damaged mitrochondria can leak toxic reactive oxygen species + acts as internal anti-aging system to keep cells healthy and functional

w/ apoptosis vs. necrosis

apoptosis doesn’t harm nearby tissue

• type 1: programmed cell death

• type 2: autophagic cell death

aging

normal + inevitable; result of accumulation of damaged macromolecules

theories of aging

• programmed theory: aging follows biological schedules encoded in genes; lifespan regulated by genes + cells follow predetermined replication limits

• damaged or error theories: aging results from accumulated damage over time; increase in free radicals’ effects on cells, structural alterations