Chapter 4: Altered Cellular and Tissue Biology

Question 1

Cellular Adaptation

Answer 1

1. Cellular adaptation is a reversible event involving a structural or functional response to both physiologic (normal) conditions and to pathologic (adverse) conditions. Cells adapt to meet physiologic
   demands and stress in an effort to maintain a steady state called
   homeostasis.
2. The most significant adaptive changes include atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia.
3. Atrophy is a decrease in cellular size caused by aging, disuse, or insufficient blood supply. Insufficient hormonal or neural stimulation also can cause atrophy. Endoplasmic reticulum, mitochondria, and microfilaments decrease with atrophy. Mechanisms predisposing the cell to atrophy include decreased protein synthesis or increased protein catabolism, or both.
4. Hypertrophy is an increase in the size of cells in response to mechanical stimuli (e.g., stretching, pressure, or volume overload) and results
   in increased size of the affected organ. Hypertrophy can be either physiologic or pathologic, depending on the circumstances.
5. Hyperplasia is an increase in the number of cells caused by an increased rate of mitosis (cell division). Hyperplasia can be physiologic (compensatory and hormonal) or pathologic hormonal.
6. Metaplasia is the reversible replacement of one mature cell type with another less mature cell type. It is found in association with tissue damage, repair, and regeneration.
7. Dysplasia, or atypical hyperplasia, is an abnormal change in the size, shape, and organization of mature tissue cells. It is considered an atypical rather than a true adaptation response.

Question 2

Cellular Injury

Answer 2

1. Injury to cells and to the extracellular matrix leads to tissue and organ injury. This injury affects the structural patterns of disease. Cellular injury occurs when the cell fails to maintain homeostasis (normal or adaptive steady state) secondary to insult or stress. Injured cells may recover (reversible injury) or die (irreversible injury).
2. Biochemical events result in characterize cell injury and death, including:
   * ATP depletion, resulting in mitochondrial damage
   * Accumulation of oxygen and radical oxygen species (ROS) which cause membrane damage
   * Increased intracellular calcium concentration and the loss of calcium steady state
   * Mitochondrial damage causing loss of membrane potential and activation of cell
   death
   * Membrane damage
   * Protein folding defects.
3. The most common forms of cell injury include ischemic and hypoxic injury, ischemia-reperfusion injury, oxidative stress or accumulation of oxygen-derived free radical-induced injury, and chemical injury.
4. Hypoxia is the lack of sufficient oxygen in cells and is the most common cause of cellular injury. The most common cause of hypoxia is ischemia, or a reduced supply of blood.
5. Restoration of oxygen in ischemic states can result in additional injury, called reperfusion injury. The mechanisms for such injury include oxidative stress, increased intracellular calcium concentration, inflammation, and complement activation.
6. Free radicals have an unpaired electron making the molecule unstable. Seeking stability, they may form chemical bonds with proteins, lipids, and carbohydrates located within membranes and nucleic acids (DNA), causing injury. The damaging effects of free
   radicals is termed oxidative stress. Mechanisms include; * Peroxidation of lipids
   * Alteration of ion pumps and transportmechanisms
   * Fragmentation of DNA
   * Damage to mitochondria, releasing calcium into the cytosol.
7. Humans are exposed to thousands of chemicals for which there is inadequate toxicologic data. Potential mechanisms for injury include oxidative stress, heat shock proteins, DNA damage, hypoxia, ER
   stress, mental stress, inflammation, and osmotic stress.
8. The world’s largest single environmental health risk is air pollution. Millions of deaths and diseases occur because of indoor and outdoor
   air pollution.
9. The most common heavy metals associated with cell injury include lead, mercury, arsenic, and cadmium. Damage from metals affects DNA repair mechanisms, tumor suppressor functions, and signal
   transduction pathways.
10. Alcohol contributes to cell injury by altering nutritional status, causing the metabolism of acetaldehyde (toxic and known carcinogen), and effecting the liver, CNS, and other body tissues.
    Chronic alcoholism and binge drinking have significant health hazards including alcoholic liver disease, cirrhosis, and hepatocellular carcinoma.
11. Fetal alcohol spectrum disorders are a range of health effects or disorders of prenatal alcohol exposure. Maternal ingestion of alcohol can be catastrophic for the developing fetus.
12. The use of psychoactive and narcotic drugs is a major problem in many parts of the world. Both prescription and illicit opiates are the main causes of drug overdose deaths.
13. Unintentional and intentional injuries are a major health problem in the United States. Death as a result of these injuries is more common for men than women and there are differences among ethnic/racial groups.
14. Injuries by blunt force are the result of the application of mechanical energy to the body, resulting in tearing, shearing, or crushing of tissues. These include contusions (bruises), lacerations (tears or rips in the skin), and fractures of bone. The most common
    causes of blunt-force injuries include motor vehicle accidents and falls.
15. Injuries by sharp force are the result of cutting or piercing. Examples of this include incised, stab, puncture, and chopping wounds.
16. Gunshot wounds may be either penetrating (bullet is retained in the body) or perforating (bullet exits the body). The most important factors determining the appearance of a gunshot injury are whether it is an entrance or an exit wound and the range at which the bullet was fired.
17. Asphyxial injuries are caused by mechanisms that prevent oxygen from entering the body and reaching the cells. These injuries can be grouped into four general categories: suffocation, strangulation, chemical asphyxiation, and drowning.
18. Activation of inflammation and immunity that follows cell injury or infection produces powerful biochemical reactions and proteins capable of damaging normal cells.
19. Genetic disorders result in cellular injury by altering the nucleus and the plasma membrane (structure, shape, receptors, or transport
    mechanisms).
20. Deprivation and excessive consumption of essential nutrients (proteins, carbohydrates, lipids, vitamins) can result in cellular injury by altering cellular structure and function.
21. Environmental factors can result in cellular injury. Common triggers include temperature extremes, changes in atmospheric pressure, ionizing radiation, illumination, mechanical stresses, and excessive
    noise.

Question 3

Manifestations of Cellular Injury

Answer 3

1. Metabolic derangements can trigger cellular injury, especially cellular accumulations. Intracellular accumulation of substances is
   called infiltration. Infiltrations include;
   * Excess accumulation of normal cellular substances (water, proteins, lipids, and carbohydrate excesses), and
   * Concentration or accumulation of abnormal substances which can be either endogenous (produced within the body, such as from abnormal metabolism) or exogenous (derived from outside the body, like a virus).
2. Most accumulations occur secondary to one of four mechanisms:
   * A normal substances that is insufficiently removed due to altered transport
   * An abnormal substance, often secondary to
   a gene mutation, accumulates;
   * An endogenous substance that is inadequately catabolized; and
   * An inhaled or ingested harmful exogenous substance accumulates or is produced secondary to an
   infection.
3. Protein accumulations injure cells by “crowding” the organelles and producing potentially harmful metabolites. Metabolites are released into the cytoplasm or expelled in the extracellular matrix. They may be abnormal substances or normal metabolites produced
   in excessive amounts.
4. Oncosis is a type of cell death that occurs secondary to cellular swelling with water. It is seen in many types of cellular injury and occurs as a result of a failure of the transport mechanisms to regulate water flow into and out of the cell.
5. Certain metabolic disorders result in abnormal intracellular accumulations of carbohydrates and lipids, primarily in the spleen, liver, and CNS.
6. Glycogen (the storage form of glucose) is an important source of energy in normal cell function, but intracellular accumulations of it can have detrimental effects on growth and development.
7. Protein accumulations primarily occur in epithelial cells of renal convoluted tubules and in the antibody B-lymphocytes.
8. Pigment accumulations can be endogenous (e.g., melanin and blood proteins) or exogenous (e.g., coal dust and other mineral dusts).
9. Dystrophic calcification is the accumulation of calcium salts in injured or dead cells, and is a sign of pathologic change. Metastatic calcification occurs in uninjured cells secondary to hypercalcemia.
10. Gout, a very common and painful disorder, results from disturbances in urate metabolism. It occurs secondary to hyperuricemia where sodium urate crystals are deposited into tissues.
11. Systemic manifestations of cellular injury initiate inflammation with associated manifestations, including fever, leukocytosis, increased heart rate, pain, and serum elevations of plasma enzymes.
12. Inflammation promotes systemic manifestations of cellular injury, including fever, fatigue, malaise, pain, altered appetite, increased heart rate, increased number of leukocytes, or the presence of cellular enzymes.

Question 4

Cellular Death

Answer 4

1. Historically, cell death has been classified as either necrosis or apoptosis. Necrosis is characterized by a rapid loss of the plasma membrane structure, organelle swelling, mitochondrial dysfunction, and the lack of any hallmark features of apoptosis. Apoptosis is known as regulated or programmed cell death and is characterized by the “dropping off” of cellular fragments, called apoptotic bodies.
2. It is now understood that under certain conditions, necrosis is regulated or programmed, hence, the new term programmed necrosis or necroptosis.
3. There are four major types of necrosis: coagulative, liquefactive, caseous, and fatty. Different types of necrosis occur in different tissues and under differing disease circumstances.
4. Gangrenous necrosis, or gangrene, is not a type of cell death but rather refers to large areas of tissue death. It is tissue necrosis caused by hypoxia and subsequent infection with anaerobic bacteria.
5. Structural signs which indicate irreversible injury with subsequent progression to necrosis are;
   * Dense clumping and disruption of
   nuclear genetic material &
   * Disruption of plasma and organelle
   membranes.
6. Apoptosis is a distinct type of selective cellular self-destruction that occurs in both normal and pathologic tissue changes. Death by apoptosis results in the loss of cells and occurs in many pathologic
   states:
   (a) severe cell injury,
   (b) accumulation of misfolded proteins,
   (c) infections
   (d) obstruction in tissue ducts.
7. Excessive or insufficient apoptosis is known as dysregulated apoptosis.
8. Autophagy, defined as the “eating of self,” is a self-destructive process. It serves as a survival mechanisms and has been compared to a “recycling factory.” When cells are starved or nutrient deprived, autophagy initiates cannibalization to recycle digested contents. Autophagy can maintain cellular metabolism under conditions of
   starvation and can remove damaged organelles under stress conditions. Autophagy declines and becomes less efficient as cells age, a dynamic, which contributes to the aging process.

Question 5

Aging and Altered Cellular and Tissue Biology

Answer 5

1. It is difficult to distinguish physiologic (normal) from pathologic (abnormal) changes associated with aging. Investigators are focused on genetic, inflammatory, oxidation, and metabolic origins of aging.
2. Important factors in aging include increased damage to cells, reduced capacity for mitosis, reduced ability to repair DNA damage, and defective nitrogen balance.
3. Frailty is a common clinical syndrome in older adults characterized by overall weakness, decreased stamina, and functional decline. This leaves the individual vulnerable to falls, functional decline, disability,
   disease, and, eventually, death. Sarcopenia and cachexia are common sequela of aging.

Question 6

Somatic Death

Answer 6

1. Somatic death is death of the entire organism. Postmortem changes are diffuse, predictable, and do not involve an inflammatory response.
2. Manifestations of somatic death are progressive, occurring in a sequenced manner. Death typically begins with the cessation of respiration and circulation and characteristic dilation of the pupils and culminates with the skeletonization of the body. The seven
   stages of death are
   (a) Pallor mortis
   (b) Algor mortis
   (c) Rigor mortis
   (d) Livor mortis
   (e) Putrefaction
   (f) Decomposition
   (e) Skeletonization
3. Depending on the environment surrounding the bones, a rare eighth stage, fossilization, may occur.

Question 7

Question 1

Answer 7

Which of the following is the most common cause of cellular injury?

A. Hypoxia
B. Chemical injury from drugs
C. Free radical–induced injury
D. Chemical injury from pollutants

Correct Answer: A

Hypoxia is caused by decreased oxygen in the environment, decreased hemoglobin, decreased red blood cells, or cardiovascular collapse and is the most common cause of cellular injury. Chemical injuries and free radical-induced injuries are other types of cell injuries but are not the most common.

Question 8

Question 2

Answer 8

Which type of necrosis best describes death of a cell from hypoxia, generally as a result of ischemia in the lower extremities?

A. Fat
B. Coagulative
C. Liquefactive
D. Gangrenous

Correct Answer: D

Gangrenous necrosis typically occurs in lower extremities when blood vessels are blocked and ischemia occurs. Hypoxia then ensues and bacteria invade. Coagulative necrosis occurs primarily in the kidneys, heart, and adrenal glands and is caused by protein degradation. Liquefactive necrosis results from ischemic injury to the neurons and glial cells. Fat necrosis occurs in the breast, pancreas, and other abdominal structures and is caused by the cellular dissolution of enzymes called lipases.

Question 9

Question 3

Answer 9

Which statement is TRUE with regard to cellular change due to aging?

A. The cellular changes are reversible.
B. DNA becomes less susceptible to injurious stimuli.
C. The cellular changes proceed slowly and in small increments.
D. Lipid, calcium, and plasma proteins are less likely to be deposited in vessel walls.

Correct Answer: C

Aging has been defined as the time-dependent loss of structure and function that proceeds slowly and in such small increments that it appears to be the result of the accumulation of small, imperceptible injuries—a gradual result of “wear and tear.” Cellular changes due to aging are irreversible. In the aged cell, DNA, RNA, cellular proteins, and membranes are more susceptible to injurious stimuli. With aging, lipid, calcium, and plasma proteins are deposited in vessel walls. These deposits cause serious basement membrane thickening and alterations in smooth muscle functioning, resulting in arteriosclerosis (a progressive disease that causes such problems as stroke, myocardial infarction, renal disease, and peripheral vascular disease).