pathophysiology chapter 4

CELL INJURY, AGING, AND DEATH

Chapter 4

1

REVERSIBLE CELL INJURY• Hydropic swelling: cellular swelling due to

accumulation of water• First manifestation of most forms of reversible cell

injury• Results from malfunction of sodium-potassium

pump with accumulation of sodium ions within the cell

• Any injury that results in loss of energy (ATP) will also result in swelling

2

REVERSIBLE CELL INJURY (CONT.)

3

REVERSIBLE CELL INJURY• Hydropic swelling: cellular swelling due to

accumulation of water• Characterized by large, pale

cytoplasm; dilated endoplasmic reticulum; and swollen mitochondria

• Generalized swelling of cells in organs can lead to increase in size and weight, indicated by “megaly”

4


Intracellular Accumulations• Excess accumulations of substances in cells

may lead to cellular injury due to toxicity, immune response, and/or taking up cellular space

• Characterized by:• Excessive amounts of normal intracellular

substance

5


Intracellular Accumulations• Characterized by

• Accumulation of abnormal substances secondary to faulty metabolism or synthesis

• Accumulation of pigments or particles that cell is unable to degrade

• Common site of accumulation is liver

6


7


8


9


10

CELLULAR ADAPTATION• Atrophy: cells shrink and reduce their

differentiated functions in response to normal and injurious factors• General causes

• Disuse• Denervation• Ischemia• Nutrient starvation• Interruption of endocrine signals• Persistent cell injury• Aging

11

CELLULAR ADAPTATION (CONT.)

12

CELLULAR ADAPTATION (CONT.)• Hypertrophy: increase in cell mass

accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands

13

CELLULAR ADAPTATION (CONT.)

14

CELLULAR ADAPTATION (CONT.)• Hyperplasia: increase in functional capacity

related to an increase in cell number due to mitotic division• Usually in response to increased physiologic

demands or hormonal stimulation

15

CELLULAR ADAPTATION (CONT.)• Metaplasia: replacement of one

differentiated cell type with another• Most often as an adaptation to persistent injury,

with replacement of a cell type that is better suited to tolerate injurious stimulation

• Fully reversible when injurious stimulation is removed

16

CELLULAR ADAPTATION (CONT.)• Dysplasia: disorganized appearance of cells

because of abnormal variations in size, shape, and arrangement• Represents an adaptive effort gone astray• Significant potential to transform into cancerous

cells, thus referred to as preneoplastic lesions

17

IRREVERSIBLE CELL INJURYNecrosis• Usually occurs as a consequence of

ischemia or toxic injury• Characterized by cell rupture, spilling of

contents into extracellular fluid, and inflammation

18

IRREVERSIBLE CELL INJURY (CONT.)

19


Four Types of Tissue Necrosis• Coagulative (most common type): process

that begins with ischemia and ends with degradation of plasma membrane

• Liquefactive: occurs with dissolution of dead cells, liquification of lysosomal enzymes, and formation of abscess or cyst from dissolved dead tissue

20


Four Types of Tissue Necrosis• Fat necrosis

• Death of adipose tissue• Usually the result of trauma or pancreatitis• Appears as a chalky white area of tissue

• Caseous necrosis• Characteristic of lung damage secondary to tuberculosis• Resembles clumpy cheese

21


22


23


Gangrene• Cellular death in a large area of tissue• Results from interruption of blood supply to

a particular part of the body• Dry gangrene

• Form of coagulative necrosis characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue

24


Gangrene• Wet gangrene

• Form of liquefactive necrosis• Typically found in internal organs

• Gas gangrene• Results from infection of necrotic tissue by

anaerobic bacteria (Clostridium), which is characterized by formation of gas bubbles in damaged muscle tissue

25


Apoptosis• Occurs in response to injury that does not

directly kill the cell, but triggers intracellular cascades that activate a cellular suicide response

• Not always a pathologic process• Does not cause inflammation

26


Two Types of Environmental or ExtrinsicSignals May Induce Apoptosis• Withdrawal of “survival” signals that

normally suppress apoptotic pathways, such as observed with cancer cells

• Extracellular signals, such as the Fas ligand, bind to the cell and trigger death cascade through activation of “death receptors”

27


28


29


• Apoptosis can also be triggered by intrinsic pathways• In response to severe cell damage, a protein (p53,

which is normally low in the body) will increase in response to cellular DNA damage, triggering the cell’s own death

• Involves numerous intracellular signals and enzymes

30


31

ETIOLOGY OF CELLULAR INJURYIschemia and Hypoxic Injury• Tissue hypoxia is most often caused by

ischemia• Ischemia is the most common cause of cell

injury and injures cells faster than hypoxia alone

• Combination of disruption of oxygen supply with accumulation of metabolic waste

32

ETIOLOGY OF CELLULAR INJURY (CONT.)

Gangrene• Cellular events lead to lactic acidosis

• Cellular proteins and enzymes become more dysfunctional

• Up to a point, ischemic injury is reversible, but cell death occurs when plasma, mitochondrial, and lysosomal membranes are critically damaged

33


34


Nutritional Injury• Adequate amounts of fats, carbohydrates,

proteins, vitamins, and minerals are essential for normal cellular function

• Certain cell types more susceptible to injury than others

35


Nutritional Injury• Nutritional deficiencies may result from Poor intake Altered absorption Impaired distribution by circulatory

system Inefficient cellular uptake

36


Nutritional Injury• Common causes of malnutrition

• Poverty• Chronic alcoholism• Acute and/or chronic illness• Self-imposed dietary restrictions• Malabsorption syndromes

• Nutritional excesses primarily result from excessive intake

37


Infectious and Immunologic Injury• Bacteria and viruses can injure cells in a

variety of ways depending on it’s virulence• Added injury may occur indirectly by

triggering body’s immune response

38


Chemical Injury• Toxic chemicals or poisons can cause

cellular injury both indirectly and by becoming metabolized into reactive chemicals by the body

39


Physical and Mechanical Injury• Factors

• Extremes in temperature• Abrupt changes in atmospheric pressure• Mechanical deformation• Electricity• Ionizing radiation

40


41


42


43

CELLULAR AGINGCellular Basis of Aging • Cumulative result of progressive decline in

proliferation and reparative capacity of cells combined with exposure to environmental factors that cause accumulation of cellular and molecular damage

• Responsible mechanisms include DNA damage, reduced proliferation capacity of stem cells, and accumulation of metabolic damage

44

CELLULAR AGING (CONT.)

45

CELLULAR AGING (CONT.)Physiologic Changes of Aging• Age-related decrease in functional reserve• Inability to adapt to environmental demand

46

SOMATIC DEATH• Death of the entire organism• No inflammation or immunologic response

occurs prior to death• General features include cessation of

respirations and heartbeat

47

SOMATIC DEATH (CONT.)• Presence of stiffened muscles throughout

body after death (rigor mortis) eventually leads to release of lytic enzymes in body tissues, postmortem autolysis

• Determination of “brain death” as proof of somatic death

48

pathophysiology chapter 4

Education