Chapter 4: Cell injury, aging, and death

cellular stress and injury

cells are confronted by many challenges to their integrity and survival and have efficient mechanisms for coping with an altered cellular environment

• cells are the basic unit of life

• stress disrupts normal cell function

• injury occurs when stress exceeds capacity

cells respond to environmental changes or injuries by

1. reversible cell injury

2. adaptation

3. irreversible cell injury (cell death)

reversible cell injury

when change is mild or short lived, cell may withstand the assault and completely return to normal

• hydropic swelling

• intracellular accumulations

adaptation

when cell adapts to a persistent but sublethal injury by changing its structure or function (can be reversible)

irreversible cell injury (cell death)

when cell injury is too server or prolonged, cell death can occur by 2 different processes (pathologic cellular death occurs when an injury is too severe or prolonged to allow cellular adaptation or repair)

1. necrosis

2. apoptosis

necrosis

(cell death by external injury; inflammatory) occurs as a consequence of ischemia or toxic injury and is characterize by cell rupture, spilling of contents into extracellular fluid and inflammation

• four types

apoptosis

cell death by intracellular signaling cascades, activation of cellular death pathway resulting in regulated cell death when cells are no longer needed (non-inflammatory)

hypoxia

lack of oxygen that results in power failure within the cell

ischemia

inadequate delivery of blood to the cells, interruption of blood flow to an area (cell death resulting from this may be slow to develop)

physical agents

causes direct destruction of tissues by directly disrupting cellular structures (frostbite, heat, burns, mechanical forces, sudden pressure change) or by cutting off blood supply (vasoconstriction, vascular obstruction) ultimately causing ischemia and death

chemical agents

toxic chemicals cause cellular injury directly or others become injurious only when metabolized into reactive chemicals by the body (chemicals may interfere with normal metabolic processes in the cell)

infectious agents

bacteria and viruses are common infectious agents that may injure cells in a variety of ways, some of the injurious effects come directly from the biological agent but added injury may be done indirectly by triggering the bodys immune response.

nutritional injury

cell injury results from deficiencies as well as excesses of essential nutrients (results from poor intake, altered absorption, impaired distribution by the circulatory system or inefficient cellular uptake)

• i.e. vitamin D deficiency affects bones

• i.e. iron deficiency primary affects RBCs

• deficiencies = fats, carbs, proteins, vitamins, and minerals

• excesses

  • BMI greater than 25kg = health risk

  • BMI greater than 30 kg = obesity

hydropic swelling

cellular swelling attributable to accumulation of water; first manifestation of most forms of reversible cell injury

• results form malfunction of the sodium - potassium pumps that normally maintain iconic equilibrium of the cell

intracellular accumulations

excess accumulations of substances in cells may result in cellular injury because the substances are toxic or provoke an immune response, or merely because they occupy space needed for cellular functions

• categorized as cellular adaption

cellular adaption

the cellular response to persistent, sublethal stress reflects the cell’s efforts to adopt common adaptive responses

1. atrophy

2. hypertrophy

3. hyperplasia

4. metaplasia

5. dysplasia

atrophy

(decreased cell size)

occurs when cells shrink and reduce their differentiated functions in response to a variety of normal and injurious factors

cause:

• disuse

• denervation

• ischemia

• nutrient starvation

• persistent cell injury

hypertrophy

(increased cell size)

increase in cell mass accompanied by an augmented functional capacity

cause:

• response to increase physiologic or pathophysiologic demands

hyperplasia

(increased cell number)

increase their functional capacity by increasing the number of cells

cause:

• increased by physiologic demands or hormonal stimulation

• persistent cell injury

metaplasia

(conversion of one cell type to another)

replacement of one differentiated cell type with another (fully reversible when injurious stimulation is removed)

cause:

• adaptation to persistent injury with replacement of a cell type that is better suited to tolerate injurious stimulation

dysplasia

(disorderly growth)

disorganized appearance of cells because of abnormal variations in size, shape, and arrangement

cause:

• adaptive effort gone astray

pathologic cellular death

a cell dies because it has been damaged by a disease, injury, or abnormal condition

four types of tissue necrosis

(when neighboring cells die, we can describe the appearance of dead tissue as particular type)

1. coagulative necrosis

2. liquefactive necrosis

3. fat necrosis

4. caseous necrosis

coagulative necrosis

(most common; dead tissue becomes relatively firm and solid) the steps leading to this

1. ischemic cellular injury that leads to

2. loss of plasma membranes ability to maintain electrochemical gradients, which result in

3. an influx of calcium ions and mitochondrial dysfunction

4. degration of plasma membranes and nuclear structures

(ie. blocked artery = ischemia = irreversible cell injury = cell death = coagulative necrosis)

liquefactive necrosis

the dissolution of dead cells occurs very quickly = liquified area of lysosomal enzymes and dissolved tissues may result and form an abscess

fat necrosis

the death of adipose tissue, usually resulting from trauma and pancreatitis (chalky white area)

1. begins with release of activated digestive enzymes from the pancreas or injured tissues

2. enzymes attack the cell membranes of fat cells causing release of their stores of triglycerides

3. pancreatic lipase can then hydrolyze the triglycerides to free fatty acids and glycerol

caseous necrosis

characteristic of lung tissue damaged by tuberculosis

• areas of dead lung tissue are white, soft, and fragile (looks like clumpy cheese)

gangrene

describes cellular death involving a large area of tissue, usually results from interruption of the major blood supply to a particular body part like toes, leg, or bowel

the forms:

1. dry

2. wet

3. gas

dry gangrene

form of coagulative necrosis characterized by blacked, dry, wrinkled, tissue that is separated from adjacent healthy tissue by an obvious line of demarcation (occurs on extremities)

wet gangrene

form of liquefactive necrosis characterized as cold, black, and foul smelling (found in internal organs)

gas gangrene

formation of bubbles of gas in damaged tissue (result of infection of genes Clostridium)

etiology

the cause of disease

tissue hypoxia

body’s tissues are not receiving enough oxygen to meet their metabolic needs (caused by ischemia, heart failure, lung disease, RBC disorders)

reperfusion injury

most cellular damage occurs after the blood supply to the tissues have been restored

• blood flow returns

• extracellular fluid fills with large amounts of calcium

• excess calcium is dangerous

ischemia reperfusion injury

restoring blood flow to tissue that has been deprived of oxygen does not immediately rescue the cells instead the return of oxygen and calcium causes additional damage

ischemia pt 2

• inadequate blood flow, oxygen, and nutrients

• no ATP made by mitochondria

results of ischemia reperfusion injury

1. calcium overload

2. formation of reactive oxygen molecules

3. subsequent inflammation

calcium overload

in cytoplasm can trigger apoptosis or activate enzymes that degrade lipids in membranes

formation of reactive oxygen molecules

(free radicals)

• oxygen free radicals linked to initiation of inflammatory cascade

subsequent inflammation

follows the reperfusion event that leads to ongoing cellular and organ damage for days, weeks after initial event

nutritional injuries pt 2

• deficiencies result from poor intake, altered absorption, impaired distribution by circulatory or inefficient cellular uptake

• excesses primary result from excessive intake - deficient cellular uptake by one cell type may contribute to excess nutrients delivery to other cell types

• excess body fat can be measured by ration of body wright to hight to derive BMI

physical and mechanical injury

1. temp

2. atmospheric

3. mechanical

4. electricity

5. radiation

temperature

high temp - cause microvascular coagulation and may accelerate metabolic processes in cell

extreme cold - (frostbites) vasodilatory response may occur leading to intensive swelling and peripheral nerve damage in ears, nose, extremities

atmospheric

interfere with gas exchange in lungs cause the formation of gas emboli in blood stream, collapse the thorax, and rupture organs

mechanical

mild abrasions to severe lacerating trauma

electricity

occurs when cells of body act as conductors of electricity

1. disruption of neural and cardiac impulses

2. hyperthermic destruction

hyperthermic destruction

resistance to the flow of electrons results in heat production, which damages the tissues

radiation

capable of injuring cells directly by breaking chemical bonds and indirectly by generating free radicals

1. genetic damage

2. acute cell destruction

genetic damage

radiation can damage DNA inside a cell by breaking DNA strands, altering bases

acute cell destruction

radiation damages the cell so severely that cell dies outright b/c of altered DNA

causes of cell injury

1. hypoxia

2. physical agents

3. chemical agents

4. infectious agents

5. nutritional imbalances

bacteria

most damage cells from the outside

viruses

enter cell to damage from the inside

immune response

may be more damaging than the direct effects of the infectious agent

chemical injury pt 2

toxic chemicals or posions = cellular injury

• directly = ie. acetaminophen - liver damage

• indirectly = metabolized into reactive chemicals

somatic death

death of the entire organism

• no inflammation or immunologic response occurs prior to death

• general features: absence of respirations and heartbeat

• within 6 hours

  • rigor mortis

• within 24 to 48 hours

  • tissue deterioration or putrefaction

  • postmortem autolysis

role of nurse

• early recognition

• prevention

• support healthy aging