Unit 1- Altered Cellular and Tissue Biology Sunday, May 21, 2023 1:33 PM Altered Cellular and Tissue Biology The majority of diseases are caused by multiple factors acting together (multifactorial) or a sing genetically susceptible person. Injury to cells or their surrounding environment, the extracellular matrix (ECM), leads to tissue Although the normal cell is characterized by a narrow range of structural and functional constra increased demands and stress so as to maintain a steady state, called homeostasis. Cellular Adaptation Reversible response including structural or functional modifications to accommo (normal) and pathologic (adverse) changes or demands. ▪ Adaptations to pathological conditions are usually only temporarily success Adaptive changes : → Atrophy—decrease in cell size → Hypertrophy—increase in cell size → Hyperplasia—increase in cell number → Metaplasia—reversible replacement of one mature cell type by anoth type or a change in cell phenotype → Dysplasia—or deranged cellular growth, is not considered a true cell rather atypical hyperplasia gle factor interacting with a and organ damage. aints, cells can adapt to odate both physiologic sful her, less mature cell lular adaptation but Atrophy Decrease in cell size Decreases organ size if enough cells shrink Physiologic w Normal in early development Pathologic w Results from decreases in workload, pressure, use, blood supply, nutrition, stimulation Example: When breaking an arm, the arm is temporarily put in a cast for the bone to heal in position. Ma lay unused for a period of time, and begin to waste away due to their redundancy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atheroscle hormonal/neural any of the muscles in the arm erotic cerebrovascular A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atheroscle disease, resulting in reduced blood supply. Note that loss of brain substance narrows the gyri a meninges have been stripped from the right half of each specimen to reveal the surface of the Hypertrophy Increase in cell size Increases organ size Physiologic w Results from increased demand, stimulation by hormones, growth factors Pathologic w Results from chronic hemodynamic overload Examples: The muscle cells produce more proteins or myofilaments and get larger in size Hypertrophy of Cardiac Muscle in Response to Valve Disease. A, Transverse slices of a normal h hypertrophy of the left ventricle (L, normal thickness of left ventricular wall; T, thickened wall fr narrowing of aortic valve caused resistance to systolic ventricular emptying). B, Histology of car heart. C, Histology of cardiac muscle from a hypertrophied heart. Hyperplasia Increase in number of cells Increased rate of cellular division Physiologic w Compensatory—enables organs to regenerate erotic cerebrovascular and widens the sulci. The brain heart and a heart with rom heart in which severe rdiac muscle from the normal Hyperplasia Increase in number of cells Increased rate of cellular division Physiologic w Compensatory—enables organs to regenerate w Hormonal—in organs that respond to endocrine hormonal control (For exam phase of the menstrual cycle, estrogen secretion by the ovary results in hyperplasia and e Pathologic w Hormonal—abnormal proliferation of normal cells Examples: Increase in the size of the breasts during pregnancy, increase in thickness of endometrium duri growth after partial resection Dysplasia Abnormal changes in size, shape, organization of mature cells May be reversible if triggering stimulus is removed Tissue appears disorderly, but is not cancer If changes penetrate basement membrane: invasive neoplasm Example: Cartilage in the various types of chondrodysplasias that result in dwarfism mple, during the follicular endometrial proliferation) ing menstrual cycle, and liver Tissue appears disorderly, but is not cancer If changes penetrate basement membrane: invasive neoplasm Example: Cartilage in the various types of chondrodysplasias that result in dwarfism Metaplasia Reversible replacement of one mature cell type by another Associated with tissue damage, repair, regeneration Reprogramming of stem cells or undifferentiated mesenchymal cells Example: The long-term cigarette smoker, the chronic irritation from smoke causes the normal ciliated co trachea and bronchi to become replaced by stratified squamous epithelial cells ) Metaplasia and dysplasia in bronchial cells olumnar epithelial cells of the Example: The long-term cigarette smoker, the chronic irritation from smoke causes the normal ciliated co trachea and bronchi to become replaced by stratified squamous epithelial cells ) Metaplasia and dysplasia in bronchial cells Cellular Injury Start of most diseases Loss of function results from cell injury and cell death Occurs when cell is unable to maintain homeostasis Injury may be reversible or irreversible The most common forms of cell injury include: ○ ischemic and hypoxic injury ○ ischemia–reperfusion injury ○ oxidative stress or accumulation of oxygen-derived free radicals-induc ○ chemical injury olumnar epithelial cells of the ced injury ○ ischemia–reperfusion injury ○ oxidative stress or accumulation of oxygen-derived free radicals-induc ○ chemical injury Agents that Cause Cellular Injury ► Physical Agents ○ Mechanical forces ○ Extremes in temperature ○ Electrical forces ► Radiation Injury ○ Ionizing radiation ○ Ultraviolet radiation ced injury ► ► ► ► ○ Extremes in temperature ○ Electrical forces Radiation Injury ○ Ionizing radiation ○ Ultraviolet radiation ○ Nonionizing radiation (U/S, microwaves) Chemical Injury ○ Drugs ○ Lead toxicity Biologic Agents Nutritional Imbalances Mechanisms of Cellular Injury Hypoxic injury Single most common cause of cellular injury Results from: ▪ Ischemia—reduced supply of blood ▪ Reduced oxygen content in ambient air ▪ Loss of hemoglobin ▪ Decreased production of red blood cells ▪ Diseases of the respiratory and cardiovascular systems ▪ Poisoning of the oxidative enzymes (cytochromes) within the cells Anoxia - total lack of oxygen caused by obstruction Ischemia- reperfusion injury Cell injury and death caused by restoration of blood flow and oxygen Restoration of blood flow and oxygen to ischemic tissues can increase recovery of cells reversib result in additional injury known as ischemia-reperfusion injury (reperfusion [reoxygenation] in Mechanisms: • Oxidative stress (Reoxygenation induces oxidative stress by generating highly ROS and nitrogen species) • Increased intracellular calcium concentration (Intracellular and mitochondrial calcium accumulate within the cell during acute ischemia more calcium influx because of damaged cell membranes and ROS-mediated injury to the • Inflammation (Ischemic injury promotes inflammation. Dead cells stimulate immune cells to release cyt signals, thus initiating an inflammatory response) • Complement activation bly injured, but paradoxically njury) and cause cell death a. Reperfusion results in even e sarcoplasmic reticulum) tokine-mediated danger more calcium influx because of damaged cell membranes and ROS-mediated injury to the • Inflammation (Ischemic injury promotes inflammation. Dead cells stimulate immune cells to release cyt signals, thus initiating an inflammatory response) • Complement activation (Complement activation may exacerbate damage which has occurred secondary to reper e sarcoplasmic reticulum) tokine-mediated danger rfusion injury.) Free radicals and reactive oxygen species Cause oxidative stress Free radical is electrically uncharged atom or group of atoms with an unpaired el Free radicals also cause damaging effects such as: • Lipid peroxidation ○ Destruction of polyunsaturated lipids (membrane damage) • Alterations of proteins • Alterations of DNA • Damage to mitochondria Role of reactive oxygen species in cell injury : Chemical or toxic injury Xenobiotics - compounds that have Toxic, mutagenic or carcinogenic properties - Carbon tetrachloride - Lead - Carbon monoxide lectron Chemical or toxic injury Xenobiotics - compounds that have Toxic, mutagenic or carcinogenic properties - Carbon tetrachloride - Lead - Carbon monoxide - Ethanol - Mercury - Social or street drugs Chemical agents including drugs Over-the-counter and prescribed drugs Opioid abuse Leading cause of child poisoning is medications Environmental toxins Air pollution (indoor and outdoor) Heavy metals Lead Cadmium and arsenic Mercury Ethanol Fetal alcohol syndrome Fetal alcohol spectrum disorders 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 - (bruise) Lacerations - (tear or rip; usually ragged and irregular with abraded edges) Fractures Contusions - (bruise) Lacerations - (tear or rip; usually ragged and irregular with abraded edges) Fractures - (blunt force blows or impact) Sharp force injuries Incised wound - (longer than deep; can be straight or jagged) Stab wound - (penetrating sharp force; deeper than long) Puncture wound - (instrument or object with sharp point but without sharp edges) Chopping wound - (heavy, edged instrument producing a combination of sharp and blunt force cha Gunshot wounds Asphyxia injuries Caused by a failure of cells to receive or use oxygen ○ Suffocation (process of dying as a result of lack of oxygen) - Choking asphyxiation : obstruction of pulmonary airway ○ Strangulation (compression of blood vessels and airway passage from exter - Hanging: use of noose or similar - Ligature: does not require suspension - Manual strangulation : when an assailants hand compressed the neck death ○ Chemical asphyxiants - Carbon monoxide - Cyanide - hydrogen sulfide ○ Drowning Infectious Injury Pathogenicity of a microorganism Disease-producing potential aracteristic) rnal pressure on neck) causes asphyxiation and Infectious Injury Pathogenicity of a microorganism Disease-producing potential • Invasion and destruction • Toxin production • Production of hypersensitivity reactions Immunologic and Inflammatory Injury Injury from substances generated during inflammatory response • Phagocytes • Biochemical substances - Histamine, antibodies, lymphokines, complement system products, an • Membrane alterations Manifestations of Cellular Injury Cellular accumulations (infiltrations) ▪ Normal cellular substances - Water - Proteins - Lipids - Carbohydrates ▪ Abnormal substances - Endogenous substances - Exogenous substances Accumulations result from four mechanisms : ▪ Insufficient removal of normal substance because of altered transport (Example: steatosis, fatty changes in the liver.) ▪ Accumulation of abnormal substance because of defects (Such occurrences are usually secondary to gene mutation.) ▪ Inadequate metabolism of endogenous substance because of lack of lysoso (Example: storage diseases.) ▪ Harmful exogenous materials (Example: heavy metals and mineral dust inhalation and ingestion or the presence of pat nd proteases omal enzyme thogenic microorganisms.) (Such occurrences are usually secondary to gene mutation.) ▪ Inadequate metabolism of endogenous substance because of lack of lysoso (Example: storage diseases.) ▪ Harmful exogenous materials (Example: heavy metals and mineral dust inhalation and ingestion or the presence of pat omal enzyme thogenic microorganisms.) Cellular Death Attributed to necrosis or apoptosis Necrosis Distruction categorized by Rapid loss of plasma membrane structure, organelle s dysfunction ○ Lacks typical features of apoptosis ○ May be regulated or programmed ○ Autolysis (autodigestion) Coagulative necrosis Protein denaturation Albumin is transformed from a gelatinous, transparent state to a firm opaque su Infarct swelling, mitochondrial ubstance Coagulative necrosis of myocardium of posterior wall of left ventricle of heart. A large anemic ( apparent; note also the necrosis of papillary muscle. Liquefactive necrosis Neurons and glial cells of the brain Cells digested by own hydrolases Tissues become soft and liquefied Triggered by bacterial infection - Staphylococci, Streptococci, and Escherichia coli (white) infarct is readily Liquefactive necrosis of the brain. The area of infarction is softened as a result of liquefactive n Caseous necrosis Results from pulmonary tuberculosis infection Combination of coagulative and liquefactive necrosis Caseous necrosis. Tuberculosis of the lung, with a large area of caseous necrosis containing yell Fatty necrosis Breast and other abdominal organs Action of lipases Fatty acids combine with elements to create soaps Tissue appears opaque and chalky white necrosis low-white and cheesy debris. Action of lipases Fatty acids combine with elements to create soaps Tissue appears opaque and chalky white Fat necrosis of pancreas. Interlobular adipocytes are necrotic; these are surrounded by acute in Gangrenous necrosis Death of tissue from severe hypoxic injury no specific pattern w Dry - Skin becomes dry and shriveled, brown or black w Wet - Area becomes cold, swollen and black - Gas gangrene, caused by Clostridium Apoptosis Programmed cell death Active process of cellular self destruction Eliminates aged/injured cells. Normal part of aging. Controls tissue regeneration Normal Physiologic Process: - Destruction of cells during embrionic process nflammatory cells Active process of cellular self destruction Eliminates aged/injured cells. Normal part of aging. Controls tissue regeneration Normal Physiologic Process: - Destruction of cells during embrionic process Pathologic Process: - Alzheimer - Parkinson Necrosis Apoptosis Cell size Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis → karyorrhexis → karyolysis Fragmentation into nu fragments Plasma membrane Disrupted Intact; altered structu orientation of lipids Cellular contents Enzymatic digestion; may leak out of cell Intact; may be release Adjacent Frequent inflammation No Physiologic or Invariably pathologic (culmination of pathologic irreversible cell injury) role Often physiologic, me unwanted cells; may b some forms of cell inj deoxyribonucleic acid Autophagy Self-destructive and a survival mechanism Cytoplasmic contents delivered to lysosomes for degradation Contributes to the aging process Aging and Altered Cellular and Tissue Biology Normal physiologic process that is both universal and inevitable. Time dependent loss of structure and function that proceeds very slowly and in s that it appears to be the result of the accumulation of small, imperceptible injuri “wear and tear.” ucleosome-size ure, especially ed in apoptotic bodies eans of eliminating be pathologic after jury, especially d (DNA) damage such small increments ies—a gradual result of Aging and Altered Cellular and Tissue Biology Normal physiologic process that is both universal and inevitable. Time dependent loss of structure and function that proceeds very slowly and in s that it appears to be the result of the accumulation of small, imperceptible injuri “wear and tear.” Frailty ▪ Weakness, decreased stamina, and functional decline in older adults ▪ Increases vulnerability to falls, disability, disease, death Somatic Death Death of entire body Postmortem changes are diffuse 1. Pallor mortis Surface of Skin become pale and yellowish 2. Algor mortis Decrease in body temperature 3. Rigor mortis stiffening of muscles 0 - 24 hours after death 4. Livor mortis Blue-purple discoloration over skin due to blood settling 5. Dilated pupils begins immediately but not evident by human eyes until 2hrs post mortem; maximum 8-12 hours (no bleeding) 6. Putrefaction Tissue and organs loose cohesiveness; break down into gaseous and liquid m 24-48hrs after 7. Decomposition Organic matter is broken down into elemental matter 8. Skeletonization Tissue of the body degrade, exposing skeleton such small increments ies—a gradual result of ; reached a peak matter
