NURS 245: Cellular Adaptation, Injury, and Death Chapter 3

Pathophysiology Chapter 3

Cellular adaptations

the cell’s response to escape and protect itself from injury

Atrophy

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

Physiologic atrophy

normal, expected adaption from decreased cell activity, reduced hormone stimulation, age-related changes
EX: involution (shrinkage) of thymus, decrease in muscle mass, uterine shrinkage after menopause

Pathologic atrophy

caused by disease or abnormal conditions from decreases in workload, pressure, decreased blood supply, poor nutrition, loss of hormonal stim
Adapt by decreased protein synthesis, increased protein breakdown, activating autophagy
EX: disuse with prolonged bed rest or immobilization, muscle loss from nerve injury

Hypertrophy

increase in cell size results in enlargement of tissue or organ caused by increased work demand or hormones

Physiologic hypertrophy

normal adaptive response like muscle growth from weight training

Pathologic hypertrophy

occurs due to disease or abnormal stress like left ventricular hypertrophy from hypertension which could lead to heart failure

Hyperplasia

increase in cell number caused by increased rate of cellular division

2 types of physiologic hyperplasia

compensatory & hormonal

Compensatory hyperplasia

allows organs to regenerate like regeneration of liver after partial removal

Hormonal hyperplasia

replaces lost tissue or supports new growth like breast gland enlargement during pregna

Pathologic hyperplasia

excessive hormonal stimulation or effects of growth factors on target tissue like enlargement of the prostate in BPH

Dysplasia

deranged cellular growth, not true cellular adaptation but rather an atypical hyperplasia which usually occurs in epithelial tissues (ex: cervical dysplasia)

Metaplasia

the reversible replacement of one mature cell by another less mature cell type
adaptive response to chronic irritation, inflammation
EX: Barrett esophagus causing normal squamous lining to change to intestinal-type cells in esophagus

Cellular injury

damage that occurs when cells are exposed to stress or harmful agents beyond their ability to adapt

Reversible & irreversible injury

Reversible: cells recover if the stress is removed
Irreversible: cells die

Common causes of cellular injury

lack of oxygen (hypoxia), free radicals, toxic chemicals, infectious agents, physical and mechanical factors, immunologic reactions, genetic factors, physical trauma, nutritional imbalances

Cellular injury can lead to cell death by (order):

decrease ATP production → failure of active transport mechanisms (Na+/K+)→ cellular swelling → detachment of ribosomes from rough ER → cessation of protein synthesis → mitochondrial swelling from calcium accumulation → leakage of digestive enzymes from lysosomes → lysis of the plasma membrane

Cellular Injury mechanisms

Ischemia-Reperfusion injury
Free radicals and reactive oxygen species
Chemical or toxic injury
Cellular accumulations

Ischemia-Reperfusion Injury → Ischemia phase (low oxygen)

Cells switch to anaerobic metabolism with low ATP and ion pumps fail leading to cell swelling and calcium buildup

Ischemia-Reperfusion Injury → Reperfusion phase (blood returns)

Sudden oxygen influx leads to a burst of reactive oxygen species, radicals cause membrane damage and mitochondrial calcium overload, mitochondrial permeability transition pore

Mechanism of Ischemia-Reperfusion injury in:

tissue transplantation & ischemic syndromes like myocardial, hepatic, etc

Free radicals & ROS

Lipids: loss of membrane integrity, increased permeability, cell swelling & necrosis
Proteins: enzyme inactivation, protein fragmentation

Nucleic acids: gene mutations

Chemical or toxic injury

Lead: affects central and peripheral nervous systems

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

Manifestations of Cellular Injury

Catabolize substances that cause metabolite accumulation in cells
Von Gierke disease
Pathologic calcification

Catabolizing “stored” substances that cause metabolite accumulation in cells

Water: cellular swelling
Lipids & carbs: usually affect the liver (e.g. fatty liver)
Glycogen: observed in genetic disorders, glycogen storage diseases
Uric acid (causes gout)

Von Gierke disease (glucose-6)

glucose-6 phosphatase deficiency glycogen accumulates in liver and kidneys (enzyme that breaks down glycogen to glucose)

Pathologic calcification definition & type

Abnormal deposition of calcium salts

Dystrophic & metastatic calcification

Dystrophic calcification

calcium deposition occurs in dead or damaged tissues despite normal serum calcium levels

Metastatic calcification

calcium deposition occurs in normal tissues due to hypercalcemia

2 types of cellular death

necrosis and apoptosis

Necrosis

uncontrolled death of cells or tissues in a living organism, usually caused by injury (inflammatory changes leading to autolysis)

Apoptosis

programmed, controlled cell death that the body uses to remove unwanted, damaged, or old cells without harming nearby tissue

Process of necrosis

Pyknosis, karyorrhexis, karyolysis

Pyknosis

shrinking of the nucleus so it becomes smaller, dark, and dense

Karyorrhexis

fragmentation of the nucleus where DNA is broken into pieces

Karyolysis

nuclear dissolution and chromatin lysis where DNA is digested by enzymes and nucleus disappears

Types of necrosis

Coagulative necrosis, liquefactive necrosis, caseous necrosis, fat necrosis, gangrenous necrosis

Coagulative necrosis

Cells transformed to a gray, firm mass
protein denaturation result from activation of enzymes common in kidneys, heart, an adrenal glands

Liquefactive necrosis

hydrolytic enzymes form liquid-filled cyst or form puss common in neurons and glial cells in the brain

Caseous necrosis

cells transformed into cheese-looking substance that is walled off
TB pulmonary infection, combination of coagulative and liquefactive necrosis

Fat necrosis

occurs exclusively in adipose tissue, common in breast, pancreas, and other abdominal structures
lipases break down lipids into fatty acids

Gangrenous necrosis

considerable mass of tissue undergoes necrosis

Dry gangrenous necrosis

tissue becomes dry and shrink, skin wrinkles, and its color changes to dark brown or black (caused by severe loss of blood supply w/out significant bacterial infection)

Wet gangrenous necrosis

occurs when dead tissue becomes infected by bacteria, leading to rapid tissue breakdown and swelling

Gas gangrene

special type results from infection of tissues by one of several Clostridium bacteria

Apoptosis

programmed cellular death with a highly selective process eliminating injured and aged cells and controlling tissue regeneration

Dysregulated apoptosis

Could be excessive or insufficient and can lead to cancer, autoimmune disorders, neurodegenerative diseases, and ischemic injury

Autophagy - apoptosis

self-eating
self-destructive process & survival mechanism

Self-destructive process

Cell selectively digests its own damaged parts, old organelles, or misfolded proteins to clean house and generate energy

Survival mechanism

damaged mitochondria can leak toxic reactive oxygen species
digesting broken parts, autophagy acts as an internal anti-aging system and keeps cells healthy and functional

Aging

normal, inevitable, and universal

Programmed theories

aging follows biological schedules encoded in genes with a predetermined replication limits

Damage or error theories

aging results from accumulated damage over time; increase in free radicals’ effects on cells, structural alterations