NURS 421 Altered Cellular & Tissue Biology Fall 2023 Class(1) PDF

Altered Cellular and Tissue Biology NURS 421 Michael W. Calik, PhD Objectives Following the module on Cellular Adaptation students will be able to: ▪ Describe the cellular responses to physiological and pathologic stress – List the major cellular adaptations and describe the major changes in ph...

Altered Cellular and Tissue Biology NURS 421 Michael W. Calik, PhD Objectives Following the module on Cellular Adaptation students will be able to: ▪ Describe the cellular responses to physiological and pathologic stress – List the major cellular adaptations and describe the major changes in phenotype (including signs and symptoms) that occur in response to physiologic and pathologic stress ▪ Describe cellular changes that occur with aging ▪ List and describe the major mechanisms of cellular stress and cellular death Cellular Response to Persistent Stress Cellular Adaptation of Growth and Differentiation ▪ Adaptive changes allows stressed tissue to survive or maintain function ▪ 5 types: – Atrophy – Hypertrophy – Hyperplasia – Dysplasia – Metaplasia Concept time! ▪ Differentiate between physiological adaptation and pathological adaptation Cell adpatation ▪ Physiologic adaptation refers to cellular changes in response to normal stimulation. ▪ Pathologic adaptation relies on the same underlying mechanisms but in response to potentially damaging stimuli. Atrophy ▪ Shrinkage in cell size (not cell number) ▪ Entire organ can shrink ▪ Cells contain less endoplasmic reticulum (tissue and protein synthesis) and fewer mitochondria ▪ Causes (physiologic vs pathologic) – Disuse – Inadequate nutrition – Denervation – Ischemia or decreased blood flow – Loss of endocrine stimulation – Aging Hypertrophy ▪ Increase in cell size (not number of cells) ▪ Entire organ can increase in size – Heart and kidney particularly prone ▪ Increase in endoplasmic reticulum, mitochondria, plasma membrane ▪ Physiologic vs. pathologic – Physiologic: e.g. increased muscle size; uterus in pregnancy – Pathologic: adaptive vs. compensatory ▪ Adaptive: e.g. cardiac hypertrophy from HTN ▪ Compensatory: e.g. remaining kidney enlarges Hyperplasia ▪ Increase in number of cells (proliferation) ▪ Can take place along with hypertrophy – Note that cells that do not divide, such as cardiac/neuronal, hyperplasia does not occur ▪ Physiologic vs. pathologic – Physiologic ▪ Compensatory hyperplasia: Adaptive : e.g. liver - removal 70% and will regenerate in 2 weeks; wound healing ▪ Hormonal hyperplasia: estrogen-dependent organs (breasts, uterus) – Pathologic: due to excessive secretion of hormones/growth factors; e.g. endometrium due to imbalance of hormones; warts Metaplasia ▪ Reversible replacement of one mature cell type with another, sometimes less differentiated, cell type – e.g. ciliated columnar epithelial cells to squamous epithelial cells in the trachea ▪ Due to chronic irritation/inflammation ▪ Can lead to neoplasms (cancer) Dysplasia ▪ Derange cell growth of tissue – Cells that vary in size, shape, and organization of mature cells – Due to persistent severe injury/irritation ▪ Not a true adaptive process; sometimes termed atypical hyperplasia ▪ Can lead to neoplasms (cancer) – Cervix and respiratory tract Cellular Injury, Death, and Senescence Causes ▪ Physical Agents ▪ Radiation Injury ▪ Chemical Injury ▪ Injury from Biologic Agents (Infectious) ▪ Injury from Nutritional Imbalances ▪ Free Radical Injury ▪ Hypoxic Cell Injury ▪ Impaired Calcium Homeostasis  Causes ▪ Physical Agents – Mechanical (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, Sharp force, Gunshot wounds – Extreme of Temperature (e.g. burns, frost bite, etc.) – Electrical (e.g. burns, muscle injury, broken bones, cardiac arrhythmias, suffocation) Causes ▪ Radiation Injury – Ionizing (e.g. radiation therapy); UV (e.g. sunburn) ▪ Kill or injure cells by damaging DNA/RNA; produce free radicals) – Nonionizing (e.g. microwave ▪ Thermal  Causes ▪ Chemical Injury – Xenobiotics ▪ Carbon tetrachloride, Lead, Carbon monoxide, Ethanol, Mercury, Social or street drugs (see Table 4-6)y – Direct damage ▪ Chemicals and drugs injure cells by combining directly with critical molecular substances – Chemotherapeutic drugs, Drugs of abuse – Hypersensitivity reactions ▪ Range from mild skin rashes to immune-mediated organ failure  Causes ▪ Injury from Biologic Agents (e.g. anthrax) – Invasion and destruction – Toxin production – Production of hypersensitivity reactions Causes ▪ Injury from Nutritional Imbalances Mechanisms of Cell Injury ▪ Free Radical Injury (oxidative stress) – Electrically uncharged atom or group of atoms having an unpaired electron that damage: ▪ Lipid peroxidation ▪ Alteration of proteins ▪ Alteration of DNA ▪ Mitochondria – e.g. reactive oxygen species (ROS) Mechanisms of Cell Injury ▪ Free Radical Injury (oxidative stress) – Causes ▪ Chemical/radiation injury ▪ Inflammation ▪ O2 and other gases ▪ Aging ▪ Infections ▪ Ischemia-reperfusion injury – e.g. Stroke, ALS, CV disease etc. – Antioxidants  Mechanisms of Cell Injury ▪ Hypoxic Cell Injury – Hypoxia: Lack of sufficient oxygen ▪ Most common cause of cell 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 ▪ Asphyxial injuries: – Caused by a failure of cells to receive or use oxygen ▪ Suffocation ▪ Strangulation ▪ Chemical asphyxiants ▪ Drowning  Mechanisms of Cell Injury ▪ Hypoxic Cell Injury – Hypoxia: Lack of sufficient oxygen ▪ Most common cause of cell injury – Cellular responses: ▪ Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange ▪ Cellular swelling ▪ Vacuolation – a space or vesicle within the cytoplasm of a cell, enclosed by a membrane and typically containing fluid  Ischemic-Reperfusion Injury ▪ Hypoxic Cell Injury – 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 Mechanisms of Cell Injury ▪ Impaired Calcium Homeostasis – Cell usually maintains low cytosolic calcium. – Calcium acts as a “second messenger.” ▪ Turns on intracellular enzymes ▪ Can damage the cell Mechanisms of Cell Injury ▪ Inflammation: next week  Manifestations (S&S) of Cellular Injury: Intracellular Accumulations ▪ Buildup of substances (produced or exogenous) that cells cannot immediately use or eliminate ▪ Types: – Normal body substances in large amounts ▪ Water, lipids, carbohydrates, melanin, proteins, glycogen, calcium, and bilirubin ▪ Fatty liver: from alcoholism triglycerides – Abnormal endogenous products ▪ Tay-Sachs: lipids – Exogenous ▪ Environmental, pigments, etc. ▪ Tattoos  Manifestations (S&S) of Cellular Injury: Pathologic Calcifications ▪ Dystrophic Calcification – Macroscopic deposition of calcium salts in injured tissue – CV disease ▪ Metastatic Calcification – Macroscopic deposition of calcium salts in normal tissue due hypercalcemia  Systemic Manifestations (S&S) of Cellular Injury ▪ Fever: release of endogenous pyrogens from bacteria or macrophages; acute inflammatory response ▪ Increased heart rate: increased metabolism from fever ▪ Lab Values: – Leukocytosis: normal WBC count is 5,000-9,000/mm3 – Lactate dehydrogenase (LDH): released from RBCs, liver, kidney, skeletal muscle – Creatine kinase (CK): released from skeletal muscle, brain, heart – Aspartate aminotransferase (AST/SGOT): Released from heart, liver, skeletal muscle, kidney, pancreas – Alanine aminotransferase (ALT/SGPT): Released from liver, kidney, heart – Alkaline phosphatase (ALP): Released from liver, bone – Amylase: Released from pancreas Reversible Cell Injury and Cell Death ▪ Reversible Cell Injury Reversible Cell Injury and Cell Death ▪ Irreversible Cell Injury ▪ Cell death – Apoptosis – Necrosis  Reversible Cell Injury and Cell Death ▪ Cell death – Apoptosis: are replaced by new cells ▪ Programmed cell death – Necrosis: interferes with cell replacement and tissue regeneration; inflammation ▪ Rapid loss of plasma membrane structure, organelle swelling, mitochondrial dysfunction, autodigestion (autolysis), lacks typical features of apoptosis  Cell Death: Necrosis vs. Apoptosis Feature Necrosis Apoptosis Cell size Enlarged (swelling) Reduced Nucleus Pyknosis (shrinks, dense) or Fragmentation karyolysis (nuclear dissolution from enzymes Plasma Disrupted Intact but altered structure membrane Cellular contents Enzymatic digestion, may leak Intact, may be released in out of cell apoptotic bodies Adjacent Frequent None inflammation Physiologic or Invariably pathologic Often physiologic, may be pathologic role (culmination of irreversible cell pathologic especially after DNA injury) damage  Cell Death: Necrosis vs. Apoptosis Feature Necrosis Apoptosis Cell size Enlarged (swelling) Reduced Nucleus Pyknosis (shrinks, dense) or Fragmentation karyolysis (nuclear dissolution from enzymes Plasma Disrupted Intact but altered structure membrane Cellular contents Enzymatic digestion, may leak Intact, may be released in out of cell apoptotic bodies Adjacent Frequent None inflammation Physiologic or Invariably pathologic Often physiologic, may be pathologic role (culmination of irreversible cell pathologic especially after DNA injury) damage  Types of Necrosis ▪ Coagulation: Kidneys, heart, adrenals; from hypoxia/ischemia or chemical injury. Protein denaturation = firm, opaque state ▪ Liquefaction: Ischemic injury in neurons/glia. Hydrolytic enzymes digest tissue (pus); bacterial infection ▪ Caseous: Usually from tuberculosis; resembles clumps of cheese, enclosed by a granulomatous inflammatory wall ▪ Fat: Breast, pancreas. Lipases break down triglycerides, FFA combine with ions to make soap (saponification)  Types of Necrosis ▪ Gangrenous: Not actually a separate type but a large area of necrosis, caused by lack of blood supply – Dry gangrene: area becomes dry and shrinks, black/brown; usually from coagulative necrosis – Wet gangrene: cold, wet, pulseless; neutrophils invade, causing liquefactive necrosis; systemic – Gas gangrene: Infection by clostridium. Hydrolytic toxins from this bacteria cause bubbles of gas (crepitus) in the area of infection  Cellular Aging ▪ Cellular aging ▪ Is it programmed into the cells? – Atrophy, decreased function, and loss of – Replicative senescence cells ▪ Telomeres become too short → the cell can no longer divide. ▪ Tissue and systemic aging – Progressive stiffness and rigidity ▪ Genetic influences – Sarcopenia (loss muscle mass/strength) ▪ Is it the result of accumulated ▪ Frailty damage? – Mobility, balance, muscle strength, motor – DNA damage activity, cognition, nutrition, endurance, – Free radicals falls, fractures, and bone density – Glycation Questions? ▪ Email: [email protected] ▪ Thank you!