Chapter 04: Altered Cellular and Tissue Biology
1. Describe the cellular adaptations made in each of the following processes: atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia.
Adaptation is a reversible, structural, or functional response to both normal or physiologic conditions and adverse or pathologic conditions. ● Atrophy is a decrease or shrinkage in cell size. It is most common in skeletal, heart, secondary sex organs and the brain. Physiologic atrophy occurs with early development such as when thymus gland undergoes atrophy during childhood. Pathologic atrophy occurs as a result of decreases in workload, pressure, use, and nerve stimulation. ● Hypertrophy is an increase in size of cells and size of infected organ. Cells of the heart and kidneys are prone to enlargement. Increased size and associated with an increase in accumulation of protein in cellular components such as plasma membrane, ER, and mitochondria, and not with an increase in cellular fluid. It can be physiologic or pathologic which can be caused by specific hormone stimulation or increased functional demand. Two types of signals are mechanical signals such as stretch, and trophic signals such as growth factors, hormones, and vasoactive agents. For example, if a kidney is removed, the other kidney becomes larger. Physiologic hypertrophy is normal, however; pathologic hypertrophy is bad. An example of pathologic hypertrophy is in hypertension. ● Hyperplasia is an increase in number of cells resulting from an increased rate of cellular division. As a response to injury, it occurs when injury has been severe and prolonged long enough to cause cell death. Hyperplasia and hypertrophy go hand in hand If cells can synthesize DNA. Two types of physiologic hyperplasia are compensatory and hormonal.Compensatory hyperplasia is an adaptive mechanism that enables certain organs to regenerate. For example, compensatory hyperplasia is the callus (thickening) of the skin as a result of hyperplasia of epidermal cells in response to a mechanical stimulus. Removal of part of the liver leads to hyperplasia of the remaining liver cells (hepatocytes) to compensate for the loss. Hormonal hyperplasia occurs chiefly in estrogen-dependent organs, such as the uterus and breast.For example, when pregnancy occurs, uterus enlarges. Pathological hyperplasia is the abnormal proliferation of normal cells, usually in response to excessive hormonal stimulation or growth. For example hyperplasia of endometrium amounts to excessive menstrual bleeding. ● Dysplasia are abnormal changes in size, shape, and organization of mature cells. It is not a true adaptive process but related to hyperplasia. Also called atypical hyperplasia. It does not indicate cancer and may not progress to cancer. ● Metaplasia is the reversible replacement of 1 mature cell type by another, sometimes less differentiated cell type. Develop from a reprogramming of stem cells that exist on most epithelia or of undifferentiated mesenchymal cells present in connective tissue. For example, cigarette smoke replaces cells. Bronchial tubes are normal ciliated epithelial cells replaced with stratified squamous epithelial cells. Bronchial metaplasia can be reversed if the inducing stimulus, usually cigarettes, is removed. With prolonged exposure to the inducing stimulus, dysplasia and cancerous transformation can occur.
9. Discuss the manifestations of cellular death.
Cellular death has historically been classified as necrosis and apoptosis. necrosis is the common type of cell death with severe cell swelling and breakdown of organelles. Necrosis is characterized by rapid loss of the plasma membrane structure, organelle swelling, mitochondrial dysfunction, and the lack of features of apoptosis. Apoptosis is known as regulated or programmed cell death and is characterized by "dropping off" of cellular fragments, called apoptotic bodies. It is now understood that under certain conditions necrosis is regulated or programmed, hence the new term "programmed necrosis", or "necroptosis". Oncosis is a type of cellular death resulting from cellular swelling.
3. Identify the mechanisms and most common causes of cellular injury.
Cellular injury occurs if the cell is unable to maintain homeostasis. Most common cause is hypoxia, or lack of sufficient oxygen. Results from reduced amount of oxygen in air, loss of hemoglobin or decreased efficacy of hemoglobin, decreased production of RBC, and poisoning of the oxidative enzymes within cells. Ischemia is the most common cause of hypoxia, or reduced blood supply. It is often caused by gradual narrowing of arteries. Reduction of ATP levels results in an increase in calcium and sodium, and potassium out of cell and water comes in.
6. Describe the major mechanism of tissue damage caused by chemical agents.
Humans exposed to xenobiotics (toxic, mutagenic chemicals) transported in the blood by lipoproteins and penetrate lipid membranes. Chemicals react with cellular macromolecules and react with cell structures causing damage. There are two defense systems for counteracting the effects 1) detoxification enzymes found in the liver and 2) antioxidant systems. Site of injury is usually liver where drugs are metabolized.
10. Name and define the four major types of necrosis, giving examples of the tissue types affected by each type of necrosis.
Necrosis-Sum of cellular changes after local cell death and the process of cellular autosuggestion (autolysis). Structural signs that indicate irreversible injury and progression to necrosis are the dense clumping and disruption of genetic material and the disruption of the plasma and organelle membranes. 4 Types of necrosis: 1. Coagulative- loss of blood flow to organs (vascular areas). Kidneys, heart, adrenal glands. Protein denaturation. Abnormality in intracellular calcium 2. Liquefactive-brain injury. Digestive enzymes digest tissue. Neurons and glial cells of the brain. Hydrolytic enzymes form liquid-filled cysts or pus. Bacterial infection-staphylococci, streptococci, and E. Coli. 3. Caseous-tuberculosis-cheesy material (tubercles in lungs). Tuberculous pulmonary infection- nodules on the lungs. Combination of coagulative and liquefactive necrosis. Dead cells disintegrate, but debri not completely broken down by hydolazes 4. Fat-fat tissue. Breast, pancreas, and other abdominal organs. Action of lipase (catalyzes hydrolysis of fats). 5. Gangrenous necrosis- death of tissue, no pattern. Not major type. Gas gangrene-due to clostridium-bacteria (gas is released) Death of tissue results from severe hypoxic injury, bacterial invastion Blockage of major arteries (i.e. lower leg)/ arteriosclerosis
4. Define oxidative stress, free radicals and lipid peroxidation.
Oxidative stress occurs when excess Reactive Oxygen Species overwhelms endogenous antioxidant systems. ● Free radicals are electrically uncharged atoms or group of atoms having an unpaired electron. ● Lipid peroxidation is the destruction of unsaturated fatty acids.
8. Define unintentional and intentional injuries.
Unintentional- More common among men. Health care errors- wrong medication, wrong dose. Intentional injury: suicide, homicide Unintentional and intentional injuries are an important health problem in the United States. Death as a result of these injuries is more common for men than women and higher among blacks than whites and other racial groups. Ex: trauma, falls, asphxiation, drowning, gunshot wounds, drug overdose
2. Discuss causative factors of each of the above cellular adaptations. Know examples of each cellular adaptation.
a. Atrophy- Pathologic-disuse, Aging causes brain cells to atrophy, decrease in workload/use/nutrition Physiologic (normal)- early development- thymus gland atrophies Decreased protein synthesis/increased protein catabolism b. Hypertrophy- mechanical (stretch) and trophic signals (growth factors and vasoactive agents) increase in cellular size is related to increased accumulations of protein in cellular components ex. Removal of one kidney makes other kidney and its cells to grow larger to compensate for excess work demand ex. Muscle grows with increased work c. Hyperplasia-increased rate of cellular division, loss of epithelial, liver, or kidney cells trigger DNA synthesis and mitotic division ex. Compensatory hyperplasia- allows certain organs to regenerate (i.e. liver) Pathologic-excessive hormonal stimulation of growth factors on target cells (i.e. pregnancy- excess hormones support growth) d. Dysplasia- ex. Epithelial tissue of the cervix and respiratory tract e. Metaplasia-can be reversed if the inducing stimulus, i.e. smoking, is removed, prolonged exposure to inducing stimulus can lead to cancerous transformation ex. replacement of normal columnar ciliated epithelial cells with stratified squamous epithelial cells in bronchial tubes due to cigarette smoking
Identify the clinical manifestations of somatic death.
a. Death of the entire person; does not involve an inflammatory response b. Algor mortis-decrease in body temp c. Rigor mortis- muscle stiffening d. Livor mortis-discoloration of the skin e. Postmortem autolysis: Putrefactive changes associated with the release of enzymes and lytic dissolution
Discuss the nutritional deficiencies and mechanism of alcohol toxicity (include fetal alcohol syndrome). Discuss pathways for alcohol metabolism
acute alcoholism affects CNS chronic alcoholism affects liver and stomach FAS- alcohol enters the placenta and disrupts fetal development Vitamin B6, magnesium, thiamine, phosphorus Alcohol is metabolized by acetaldehyde in the liver by 3 enzyme systems: alcohol dehydrogenase (ADH), microsomal ethanol-oxidizing systems MEOS/CYP2E1, Catalase
11. Discuss apoptosis, and compare and contrast apoptosis and necrosis.
apoptosis -Regulated (programmed) cell death-Dropping off of fragments of the cell-May be normal part of cell cycle (not related to an injury) necrosis- the sum of cellular changes after local cell death and the process of cellular self-digestion; cellular dissolution
7. Discuss the importance of alcoholism to the etiology of disease and dysfunction.
causes liver and nutritional disorders (most serious) 1. nutritional deficiencies-Magnesium,Vit B6, thiamine, phosphorus, folic acid (pregnancy) 2. liver-Alcohol metabolized into acetaldehyde --> Toxic tissue effects-ALD 3. effects multiple organs/organ system-depresses the CNS-Cardiovascular mortality (MI, CVA)-Structural changes in liver (Cirrhosis, Liver failure) All functions of liver (over 500) may be impaired-Metabolism (nutrients, drugs, etc);-Coagulation-Albumin production (etc)
5. Describe the general mechanism of cellular injury that can occur as a result of hypoxia.
lack of sufficient oxygen is the single most common cause of cellular injury, from a decreased amount of oxygen in the air, loss of hemoglobin, decreased production of red blood cells, disease of the respiratory and cardiovascular system and poisoning, the most common is ischemia (reduced blood supply) Reduced oxygen at the cell level. Hypoxic injury- most common cause of cell injury. How does hypoxia cause cell damage? diminishes ATP production. #1 cause of hypoxia=ischemiaResults from: Reduced amount of oxygen in the air, loss of hemoglobin or decreased efficacy of hemoglobin, decreased production of red blood cells, diseases of the respiratory and cardiovascular systems, poisoning of the oxidative enzymes (cytochromes) within the cells. results from reduced amount of oxygen in the air, loss of hemoglobin, decreased production of rbc;can induce inflammation includes activation of immune
