Chapter 2: Altered Cellular and Tissue Biology PDF

Chapter 2 Altered Cellular and Tissue Biology Copyright © 2019, Elsevier Inc. All rights reserved.  Cellular Adaptation  Is the cell’s response to escape and protect itself from injury.  Adaptive changes in cells  Atrophy: Decrease in cell size  Hype...

Chapter 2 Altered Cellular and Tissue Biology Copyright © 2019, Elsevier Inc. All rights reserved.  Cellular Adaptation  Is the cell’s response to escape and protect itself from injury.  Adaptive changes in cells  Atrophy: Decrease in cell size  Hypertrophy: Increase in cell size  Hyperplasia: Increase in cell number  Metaplasia: Reversible replacement of one mature cell type by another less mature cell type  Dysplasia: Deranged cellular growth; is not a true cellular adaptation but rather an atypical hyperplasia Copyright © 2019, Elsevier Inc. All rights reserved. 2  Cellular Adaptation (Cont.) Link to video on Cellular Adaptations Copyright © 2019, Elsevier Inc. All rights reserved. 3 Cellular Adaptation (Cont.)  Cellular Adaptation (Cont.)  Atrophy  Physiologic Occurs with early development, similar to the thymus.  Pathologic Results from decreases in workload, use, pressure, blood supply, nutrition, hormonal stimulation, and nervous stimulation.  Disuse  Decreased protein synthesis, increased protein catabolism, or both Ubiquitin-proteasome pathway Copyright © 2019, Elsevier Inc. All rights reserved. 5  Cellular Adaptation (Cont.)  Hypertrophy  Caused by increased work demand or hormones. Trigger signals: Mechanical and trophic  Physiologic  Pathologic  Hyperplasia  Caused by increased rate of cellular division.  Physiologic Compensatory: Allows organs to regenerate Hormonal: Replaces lost tissue or supports new growth  Pathologic Copyright © 2019, Elsevier Inc. All rights reserved. 6  Cellular Adaptation Question 1 Which of the following statements is correct regarding pathologic hyperplasia? 1. Produces abnormal proliferation of abnormal cells. 2. Is an adaptive mechanism that enables organ regeneration. 3. Increases cell size. 4. May occur in response to growth factors. (Look for the answer in notes below the slide) Copyright © 2019, Elsevier Inc. All rights reserved. 7  Cellular Adaptation  Dysplasia  Refers to abnormal changes in the size, shape, and organization of mature cells.  Can be called atypical hyperplasia.  Does not indicate cancer.  Metaplasia  Is the reversible replacement of one mature cell by another less mature cell type. Replacement of normal bronchial columnar ciliated epithelial cells by stratified squamous epithelial cells  Is a reprogramming of stem cells. Copyright © 2019, Elsevier Inc. All rights reserved. 8  Cellular Injury  Leads to injury of tissues and organs, determining structural patterns of disease.  Injured cells may recover (reversible injury) or die (irreversible injury).  Causes cell stress.  Is acute or chronic and reversible or irreversible.  Can involve necrosis, apoptosis, accumulation, or pathologic calcification. Copyright © 2019, Elsevier Inc. All rights reserved. 9  Cellular Injury (Cont.)  Injury and Responses Copyright © 2019, Elsevier Inc. All rights reserved. 10  Cellular Injury (Cont.)  Causes  Lack of oxygen (hypoxia)  Free radicals  Toxic chemicals  Infectious agents  Physical and mechanical factors  Immunologic reactions  Genetic factors  Nutritional imbalances  Physical trauma Copyright © 2019, Elsevier Inc. All rights reserved. 11  Cellular Injury (Cont.)  Biochemical mechanisms 1. Adenosine triphosphate (ATP) depletion 2. Mitochondrial damage 3. Accumulation of oxygen and oxygen-derived free radicals 4. Membrane damage (ATP depletion) 5. Protein folding defects 6. DNA damage defects 7. Calcium level alterations Copyright © 2019, Elsevier Inc. All rights reserved. 12  Cellular Injury (Cont.)  Cellular injury can lead to cell death by:  Decreased ATP production  Failure of active transport mechanisms (sodium-potassium [Na+/K+] pump)  Cellular swelling  Detachment of ribosomes from endoplasmic reticulum  Cessation of protein synthesis  Mitochondrial swelling from calcium accumulation  Vacuolation  Leakage of digestive enzymes from lysosomes; autodigestion of intracellular structures  Lysis of the plasma membrane  Death Copyright © 2019, Elsevier Inc. All rights reserved. 13  Cellular Injury (Cont.)  Hypoxic injury  Single most common cause of cellular injury  Results 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 Copyright © 2017, Elsevier Inc. All rights reserved. 14  Cellular Injury Mechanisms (Cont.)  Hypoxic injury (Cont.)  Ischemia Most common cause of hypoxia  Ischemia-reperfusion injury Additional injury that can be caused by restoration of blood flow and oxygen Mechanisms:  Oxidative stress  Increased intracellular calcium  Inflammation  Complement activation Copyright © 2017, Elsevier Inc. All rights reserved. 15  Cellular Injury Mechanisms (Cont.)  Hypoxic injury (Cont.)  Anoxia  Cellular responses: Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange Cellular swelling Vacuolation  Reperfusion injury Copyright © 2017, Elsevier Inc. All rights reserved. 16  Process of Oncosis Link to video on hypoxia Copyright © 2017, Elsevier Inc. All rights reserved. 17  Cellular Injury (Cont.)  Ischemia-Reperfusion Injury  Due to: Oxidative stress Radicals that cause membrane damage and mitochondrial calcium overload Mitochondrial permeability transition pore  Mechanism of injury in: Tissue transplantation Ischemic syndromes: myocardial, hepatic, intestinal, cerebral, renal, stroke Copyright © 2019, Elsevier Inc. All rights reserved. 18 Free radicals and reactive oxygen species  Electrically uncharged atom or group of atoms having an unpaired electron that damage: Lipid peroxidation Alteration of proteins Alteration of DNA Mitochondria Copyright © 2017, Elsevier Inc. All rights reserved. 19 Reactive Oxygen Species Copyright © 2017, Elsevier Inc. All rights reserved. 20  Cellular Injury (Cont.)  Free radicals and reactive oxygen species (ROS)—oxidative stress  Increase of different reactive species  Detrimental oxidation of Lipids Proteins Nucleic acids  Mitochondrial effects Dysfunction caused by ROS Inefficient antioxidants Copyright © 2019, Elsevier Inc. All rights reserved. 21  Cellular Injury Question 2 A nurse knows that free radicals may be produced by 1. protein peroxidation. 2. metabolism of exogenous chemicals or drugs. 3. spontaneous decay of superoxide. 4. vitamins E and C supplements. Copyright © 2019, Elsevier Inc. All rights reserved. 22  Cellular Injury  Chemical injury  Direct toxicity to the cell Damage to or destruction of plasma membrane  Reactive free radicals and lipid peroxidation  Examples Lead Carbon monoxide Ethyl alcohol Mercury Social or street drugs Copyright © 2019, Elsevier Inc. All rights reserved. 23  Cellular Injury (Cont.)  Carbon monoxide (CO)  Is colorless and odorless.  Produces hypoxic injury. Directly reduces the oxygen-carrying capacity of blood, and promotes tissue hypoxia. CO’s affinity for hemoglobin is much greater than that of oxygen; it quickly binds with the hemoglobin, preventing oxygen molecules from doing so. Copyright © 2019, Elsevier Inc. All rights reserved. 24  Cellular Injury (Cont.)  Lead  Exposure in children can result in learning/behavior problems, speech/hearing problems, brain/nervous system damage, and slowed growth and development.  Most common source is paint in older homes (children), the environment, and at work (adults).  Toxicity affects central and peripheral nervous systems.  Prevention is the key.  Treatment may include chelation therapy. Copyright © 2019, Elsevier Inc. All rights reserved. 25  Cellular Injury (Cont.)  Ethanol (alcohol)  Results in major nutritional deficiencies, especially folate.  Is metabolized in the liver.  Has a protective effect with the cardiovascular system, up to a point.  Acute alcoholism affects the central nervous system (CNS).  Chronic alcoholism affects primarily the liver and stomach. Alcohol-induced liver disease (fatty liver, alcoholic hepatitis, cirrhosis) Acute gastritis  Can cause fetal alcohol syndrome. Copyright © 2019, Elsevier Inc. All rights reserved. 26  Cellular Injury (Cont.)  Mercury  Two major sources are fish and healthcare equipment.  Recommendation: Pregnant women, nursing mothers, and young children should avoid eating fish with a high mercury content.  Social or street drugs  Most popular and dangerous drugs include methamphetamine (“meth”), marijuana, cocaine, and heroin. Copyright © 2019, Elsevier Inc. All rights reserved. 27  Cellular Injury (Cont.)  Unintentional and intentional injury  Falls, motor vehicle injuries, opioid overdose, poisonings  Sports- and recreation-related injuries in children  Firearms  Medical care  Suicide Copyright © 2019, Elsevier Inc. All rights reserved. 28  Unintentional and Intentional Injuries  Blunt force injuries  Result of application of mechanical force to body Results in tearing, shearing, or crushing of tissues Motor vehicle accidents and falls  Contusions  Lacerations  Fractures (Refer to Table 2.9) Copyright © 2017, Elsevier Inc. All rights reserved. 29  Unintentional and Intentional Injuries (Cont.)  Sharp force injuries  Incised wound  Stab wound  Puncture wound  Chopping wound  Gunshot wounds (Refer to Table 2.9) Copyright © 2017, Elsevier Inc. All rights reserved. 30  Unintentional and Intentional Injuries (Cont.)  Asphyxial injuries:  Caused by a failure of cells to receive or use oxygen Suffocation  Choking asphyxiation Strangulation  Hanging, ligature, and manual strangulation Chemical asphyxiants  Cyanide and hydrogen sulfide Drowning Copyright © 2017, Elsevier Inc. All rights reserved. 31  Manifestations of Cellular Injury  Cellular accumulations (infiltrations)  Cells attempt to catabolize “stored” substances that cause metabolite accumulation in cells.  Water Cellular swelling  Lipids and carbohydrates Usually affect the liver (e.g., fatty liver).  Glycogen Observed in genetic disorders: Glycogen storage diseases Accumulation: Excessive vacuolation of the cytoplasm Copyright © 2019, Elsevier Inc. All rights reserved. 32 Manifestations of Cellular Injury (Cont.)  Cellular swelling Copyright © 2019, Elsevier Inc. All rights reserved. 33 Manifestations of Cellular Injury (Cont.)  Cellular accumulations (infiltrations)  Proteins Excess accumulates primarily in the renal convoluted tubule and in the immune B lymphocytes.  Pigments Melanin, hemoproteins, bilirubin  Calcium Dystrophic calcification, psammoma bodies, metastatic calcification  Urate: Uric acid Excess causes gout. Copyright © 2019, Elsevier Inc. All rights reserved. 34  Manifestations of Cellular Injury (Cont.) Accumulation of pigments Copyright © 2017, Elsevier Inc. All rights reserved. 35  Manifestations of Cellular Injury (Cont.) Calcium infiltration Copyright © 2017, Elsevier Inc. All rights reserved. 36 Manifestations of Cellular Injury (Cont.)  Systemic manifestations  Fatigue and malaise  Loss of well-being  Altered appetite  Fever  Leukocytosis  Increased heart rate  Pain  Other signs and symptoms Copyright © 2019, Elsevier Inc. All rights reserved. 37  Cellular Death  Two types of cellular death: 1. Necrosis Includes inflammatory changes. Autolysis 2. Apoptosis No inflammatory changes Type I—programmed cell death Type II—autophagic cell death Copyright © 2019, Elsevier Inc. All rights reserved. 38  Cellular Death (Cont.)  Necrosis and Apoptosis Copyright © 2019, Elsevier Inc. All rights reserved. 39  Cellular Death: Necrosis  Necrosis  Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis)  Necrosis processes  Pyknosis Shrinking of the nucleus  Karyorrhexis Fragmentation of the nucleus  Karyolysis Nuclear dissolution and chromatin lysis Copyright © 2019, Elsevier Inc. All rights reserved. 40  Cellular Death: Types of Necrosis  Coagulative necrosis  Kidneys, heart, and adrenal glands  Protein denaturation  Changes protein albumin  Liquefactive necrosis  Neurons and glial cells in the brain  Hydrolytic enzymes form liquid-filled cyst or form pus. Copyright © 2019, Elsevier Inc. All rights reserved. 41 Cellular Death: Types of Necrosis (Cont.)  Caseous necrosis  Tuberculosis pulmonary infection  Combination of coagulative and liquefactive necrosis  Cheese-looking substance that is walled off  Fat necrosis  Breast, pancreas, other abdominal structures  Action of lipases Copyright © 2019, Elsevier Inc. All rights reserved. 42 Cellular Death: Types of Necrosis (Cont.)  Gangrenous necrosis  Clinical term  Dry vs. wet gangrene  Gas gangrene Copyright © 2019, Elsevier Inc. All rights reserved. 43 Cellular Death: Types of Necrosis (Cont.)  Dry Gangrene Link to video on necrosis Copyright © 2019, Elsevier Inc. All rights reserved. 44  Cellular Death: Apoptosis  Apoptosis  Is programmed cellular death.  ER stress results in apoptotic cell death.  Is the active process of cellular destruction.  Can occur normally or pathologically.  Dysregulated apoptosis is excessive or insufficient. can lead to cancer, autoimmune disorders, neurodegenerative diseases, and ischemic injury. Copyright © 2019, Elsevier Inc. All rights reserved. 45  Cellular Death: Autophagy  “Recycling center”  Eats itself  Self-destructive process  Survival mechanism Copyright © 2019, Elsevier Inc. All rights reserved. 46  Somatic Death  Is the death of the entire person.  Does not involve an inflammatory response.  Postmortem changes include:  Complete cessation of respirations and circulation  Algor mortis: Reduced temperature  Livor mortis: Purple skin discoloration  Rigor mortis: Muscle stiffening  Postmortem autolysis: Putrefactive changes associated with the release of enzymes and lytic dissolution Copyright © 2019, Elsevier Inc. All rights reserved. 47