Pathology Textbook PDF

CHAPTER 1: BASIC TERMINOLOGY ​ Disease – Deviation in “normal” health –​ Infectious vs. Non-Infectious »​ Infectious: caused by pathogens »​ Non-infectious: not caused by pathogens –​ Idiopathic: unknown cause of disease –​ Iatrogenic: d...

CHAPTER 1: BASIC TERMINOLOGY ​ Disease – Deviation in “normal” health –​ Infectious vs. Non-Infectious »​ Infectious: caused by pathogens »​ Non-infectious: not caused by pathogens –​ Idiopathic: unknown cause of disease –​ Iatrogenic: disease caused by the treatment of another disease (drugs having side effects) –​ Acute vs. Chronic »​ Acute: short term; goes away; come on quickly »​ Chronic: long term; lifetime; develop slower –​ Diagnosis vs. Prognosis »​ Diagnosis: before treatment; past focused; what you have »​ Prognosis: future focused; follows treatment –​ Remission vs. Exacerbation »​ Remission: disease is gone; short term or long term »​ Exacerbation: disease gets worse –​ Complications: problems that arise during treatment –​ Sequelae: complications that occur because of treatment; aftermath of disease running its course (scar that you get from treatment) –​ Predisposing (Risk) Factors: factors that make you more susceptible to a disease(s) (smokers: lung cancer) –​ Clinical Manifestations:  ​ Signs vs. Symptoms »​ Signs: objective (fever, rash) »​ Symptoms: subjective (pain, stomach ache) ​ Local vs. Systemic »​ Local: one part of the body »​ Systemic: 2 or more parts of the body ​ Epithelial vs. Connective Tissues »​ Epithelial tissues: cells are packed closely together; not much space between cells »​ Connective tissues: cells are spread farther apart; more space in between cells (blood, bones, tendons, ligaments) ​ CHAPTER 4: ALTERED CELL AND TISSUE BIOLOGY ​ All cells in the body may be considered… –​ Normal: –​ Injured: –​ “Adapted”: has not suffered injury, but accommodates to the body as needed; temporarily; goes back to normal when done CELLULAR ADAPTATION –​ Atrophy – Decrease in cell size ​ Physiologic vs. Pathologic Atrophy »​ Physiologic atrophy: not part of a disease process; thymus »​ Pathologic atrophy: part of a disease process ​ Disuse Atrophy: muscle tissue; happens because of lack of use  ​ Hypertrophy – Increase in cell size –​ Physiologic vs. Pathologic Hypertrophy »​ Physiologic hypertrophy: »​ Pathologic hypertrophy: –​ Hyperplasia – Increase in cell number ​ Physiologic vs. Pathologic Hyperplasia »​ Physiologic hyperplasia: »​ Pathologic hyperplasia: ​ Compensatory Hyperplasia: when an organ or tissue changes in size or cell number to compensate for loss or damage of another tissue ​ Hormonal Hyperplasia: excessive growth of cells due to hormonal imbalance –​ Metaplasia – Cellular replacement ​ By a less mature cell – reversible ​ Normal process –​ Dysplasia – Abnormal changes in cells ​ a.k.a. atypical hyperplasia: abnormal increase in cell number ​ e.g. neoplasia: uncontrolled, abnormal growth of cells –​ Cancer CELLULAR ADAPTATION: CAUSES –​ Increase/decrease in workload –​ Increase/decrease in blood supply –​ Changes in nutrition  –​ Changes in hormones: hormone concentrations –​ Nervous system stimulation (or lack thereof) –​ Causes may be direct or indirect –​ Causes may be normal, or part of a disease process (physiologic vs. pathologic) CELLULAR INJURY –​ Reversible vs. Irreversible Injury »​ Reversible injury: can go back to normal; with or without injury »​ Irreversible injury: cannot go back to normal –​ What is the “point of no return” for injured cell? »​ Point of no return: cell is unable to return to normal; necrosis occurs –​ Features of Injured Cells: ​Severe drop in ATP production ​Water flows into cell en masse → extensive vacuolation (especially in mitochondria) –​Oncosis (a.k.a. hydropic degeneration) »​ Cells store water (compartmentalize); try to get it out of cell ​High Ca2+ infiltration into the cell ​Accumulation of oxygen-derived free radicals »​ Antioxidant vitamins: prevent this from occurring CELLULAR INJURY: CAUSES –​ (1) Hypoxia – Insufficient oxygen to cells ​Anoxia: cell completely lacks oxygen  ​Usually results from ischemia: blood deprivation to tissue ​May result from asphyxial injury to tissues: physical pressure on tissue to keep it from getting what it needs; can be intentional or unintentional ​May also lead to reperfusion injury: when a tissue deprived of oxygen is flooded with oxygen again; excess free radical concentrations –​ (2) Free Radical Damage ​Atom(s) with unpaired electrons ​Reactive Oxygen Species (ROS): toxic oxygen free radicals ​Oxidative Stress: tissue becomes injured because of overflow of oxygen ​e.g. O2–, OH–, H2O2, etc. ​ (3) Chemical Injury –​ Poisons – toxic chemical agents (xenobiotics): molecule that is not found in nature; man made poison »​ Cyanide –​ e.g. lead, CO, ethanol, drugs, etc. »​ Cyanosis: skin turns blue due to oxygen deprivation ​ (4) Infectious/Inflammatory Injury –​ Pathogens: parasite; feeds off of host & harms the host in the process  ​ (5) Traumatic Injury –​ Blunt vs. Sharp Force Injury »​ Blunt force injury: does not penetrate tissue (punch, kick); doesn’t pierce the integument »​ Sharp force injury: punctures tissue (knife) MANIFESTATIONS OF CELLULAR INJURY (INFILTRATIONS) –​ Water (vacuolation): cell takes water & stores it in vacuoles; this is so cell does not become too diluted –​ Lipids (fatty change): lipid build up in cells –​ Carbohydrates (glycogen accumulation): polymer of glucose –​ Proteins (melanin, hemoproteins, etc.) –​ Calcium ​ Dystrophic vs. Metastatic Calcification »​ Dystrophic Calcification: follows tissue injury; happens because of tissue damage »​ Metastatic Calcification: calcification comes first; damages tissue –​ Uric Acid (hyperuricemia, can lead to gout): too much uric acid in the bloodstream CELLULAR DEATH: NECROSIS –​ Cellular changes that happen after death ​Autolysis: Diseased cell dies; burst; check troponin levels to see if someone had heart attack ​Pyknosis: cell and its nucleus shrinks up; does not burst; sometimes, nucleus might lyse without the rest of cell  ​Karyolysis: (and Karyorrhexis) »​ Karyolysis: dissolution of chromatin in a dying cell (structure of cell) »​ Karyorrhexis: nucleus of a dying cell breaks down & fragments –​ Types of Necrosis ​Coagulative Necrosis (infarct): tissue dies in part or in whole; ​Liquefactive Necrosis: tissue dies & becomes liquified ​Caseous Necrosis: cheese-like; happens because of infectious disease ​Fat Necrosis (saponification): soap-like; fat accumulation in tissues ​Gangrenous Necrosis (and Gas Gangrene) »​ Gangrenous necrosis: happens because of interruption in blood supply; tissue begins to turn black; can be acute or chronic; diabetes »​ Gas gangrene: bacteria build up; lack/interruption in blood supply CELLULAR DEATH: APOPTOSIS –​ Cellular “suicide” –​ Cell initiates self-destruct program (at the genetic level) –​ Nucleus and cytoplasm shrink → fragmentation of cell –​ May happen in normal and diseased tissues CHAPTER 6: INFLAMMATION & WOUND HEALING ​ First Line of Defense –​ Non-specific: –​ Not subject to activation/deactivation: skin, chemical barriers: stomach acid, genes, microbiome creates barrier of defense, normal flora antagonizes pathogens ​ Second Line of Defense –​ Non-specific –​ Activated as needed: turned on & off as needed; fever, inflammation, interferons, complement proteins ​ Third Line of Defense –​ Specific Immunity: B & T cells ​ Vaccines INFLAMMATION –​ A non-specific, localized response to injury ​ Clinical Manifestations: –​ Redness (Erythema) –​ Swelling (Edema) –​ Heat –​ Pain –​ Loss of function (?)  ​ Acute vs. Chronic Inflammation »​ Acute inflammation: »​ Chronic inflammation: ​ Exudate –​ Fluid that infiltrates area of inflammation –​ Serous exudate: clear; water-like –​ Fibrinous exudate: cloudy; contains fibrinogen –​ Purulent exudate (abscess): pus-like; bacteria –​ Hemorrhagic exudate: ​ Granulomas may form as well »​ Granulomas: body tried to get rid; encapsulate so it does not spread ​ Largely due to degranulation of mast cells: dumping contents of granules into surrounding environment (basophils, neutrophils) –​ Immediate response chemicals: ​ Histamine: immediate, fast acting; vasodilator ​ Many WBC chemotactic factors: attracts white blood cells to the area of the body where they are needed –​ Long-term response chemicals: ​ Prostaglandins: lipids; don’t start inflammation; maintain inflammation for long as needed; interact with nervous system; send pain signals; aspirin ​ Leukotrienes: inflammatory lipids  ​ Other plasma protein systems may get involved… –​ Complement system: proteins in your blood that help your body fight infection; B cells make antibodies; defends your body against invaders –​ Clotting system: hemophilia; platelets; prevents bleeding when a blood vessel is injured THREE MAIN PHASES (Following Tissue Injury) –​ (1) Vasodilation (and ↑ in tissue permeability) ​Blood vessel diameter ↑ in area ​Influx of exudate ​Increase of blood flow ​Flow rate decreases ​Tissues become more permeable to fluid –​ (2) Phagocyte migration/phagocytosis ​Chemotaxis: when something is chemically attracted to something ​Margination (a.k.a. “pavementing”): white blood cells stick themselves to the vessel walls ​Diapedesis: squeeze in between cells to get to area where chemoattractant factor is the highest –​ (3) Repair of damaged tissues ​Regeneration vs. Repair »​ Regeneration: minimal tissue damage; tissue can regenerate back to original structure & function »​ Repair: tissue might not be made to what it was before; see the development of scar tissue  ​Reconstructive vs. Maturation Phase »​ Reconstructive: Replacing cells; rebuilding tissue »​ Maturation: Restoring the function; body starts to adopt the function of cells around it ​Primary vs. Secondary Intention »​ Primary intention: Not as serious; tissue more likely to regenerate »​ Secondary intention: More serious; tissue more likely to be repaired —------------------------------------------------------ QUIZ #1 END—------------------------------------------------------------------- —------------------------------------------------------ QUIZ #2 START—---------------------------------------------------------------- DYSFUNCTIONS IN INFLAMMATION AND WOUND HEALING –​ Hypovolemia → vessel constriction; low blood volume; body constricts blood cells to stop you from losing too much blood »​ Spleen releases reserve of cells –​ Excess bleeding = slower repair times –​ Defects in collagen synthesis (in repair phases); collagen ​Hypertrophic scarring: excess of proteins ​Keloid formation: more common on people with darker skin; synthesis of collagen & fibers is excessive ​Genetic collagen synthesis defects: healing time is slow –​ Dehiscence – “reopening” of sutured wounds –​ Wound contracture = excessive contraction CHAPTER 8: INFLAMMATION & WOUND HEALING IMMUNODEFICIENCY –​ Defect in self-defense mechanism(s) –​ Primary (Congenital) Immunodeficiency ​Born with defect (usually genetic) ​May involve B-cells (e.g. agammaglobulinemia) and/or T-cells ​SCIDs –​Severe combined immunodeficiencies: rare genetic disorders that causes problems within the immune system ​ Secondary (Acquired) Immunodeficiency –​ Contracted after birth –​ May be… ​ Nutritional immunodeficiency ​ Iatrogenic immunodeficiency ​ Trauma-induced immunodeficiency ​ Stress-induced immunodeficiency ​ The result of an infectious disease (e.g. HIV → AIDS) IMMUNODEFICIENCY- TREATMENTS –​ IVIg (and CPT) –​ Stem cell and/or bone marrow grafts –​ Gene therapy Hypersensitivity –​ Exaggerated response to injury (or to a foreign and/or benign substance) –​ Immediate vs. Delayed Hypersensitivity »​ Immediate hypersensitivity: comes on right away »​ Delayed hypersensitivity: could take weeks or days »​ Anaphylaxis: histamine is dumped in the body; causing vasodilation ​ Cutaneous vs. Systemic Anaphylaxis »​ Cutaneous anaphylaxis: smaller allergic reaction; causes blood vessels to become more permeable »​ Systemic anaphylaxis: severe allergic reaction that affects many organ systems THREE MAIN TYPES –​ (1) Allergy ​Response to allergens: reactions in the body that cause histamine release ​Neoantigens: foreign proteins that are absent in normal tissues –​ (2) Autoimmunity ​Immune system targets self (no tolerance) ​MANY types, which may happen because… –​Clonal deletion didn’t happen properly –​Immune system targets self material that closely  resembles foreign material ​ (3) Alloimmunity –​ Response to grafted tissues ​ Autograft (NO alloimmune response): graft from self; another part of your body ​ Isograft (NO alloimmune response): graft from identical twin ​ Allograft: graft from the same species ​ Xenograft: graft from a different species than your own –​ Acute vs. Chronic Rejection »​ Acute rejection: comes on faster; comes on faster; days/weeks »​ Chronic rejection: happens over time; could be weeks or months –​ Hyperacute Rejection (“white graft”): transplant rejection that occurs within hours or minutes of organ transplant or graft FOUR MECHANISMS Type I Hypersensitivity: food allergy; hives; most allergic reactions ​IgE causes mast cell degranulation → release of histamine ​Urticaria (“wheal and flare reaction”): hives ​Atopic – genetic predisposition; some people are more prone to develop allergies than others ​Desensitization for prevention –​Blocking antibodies – usually IgG class: keeps antigen away from IgE (IgG last for about a month; IgE a few days)  Type II Hypersensitivity: rejecting a graft, organ transplant, blood transfusion; body sees as nonself; hemolytic disease of the newborn: mom is Rh-, baby is Rh+; Rhogam is Rh factor ​ Antibodies bind to tissue-specific antigens: protein or cell structure unique to a specific tissue or cell ​ Many host WBCs may be involved! Type III Hypersensitivity: autoimmune disease; Raynaud's disease; tissue gets destroyed because antigens get stuck Ab-Ag complexes deposit in certain tissues –​ “Serum sickness”: immune reaction that occurs after receiving injection or medication ​ Neutrophils try to digest complex = leakage ​ Arthus Reaction: occurs when a person is reexposed to an antigen that they have previously been sensitized to ​ Raynaud Phenomenon: reduced blood flow to extremities –​ Cryoglobulins: proteins in blood that precipitate (from a solid) when exposed to cold temperatures Type IV Hypersensitivity: poison ivy, cheap jewelry; delayed response; only T-cells respond, no antibodies ​ Cell-mediated reactions ​ ONLY involve T-cells (no antibodies) ​ e.g. graft/tumor rejection, contact dermatitis, etc. —------------------------------------------------------ QUIZ #2 END—------------------------------------------------------------------ —------------------------------------------------------ QUIZ #3 START—---------------------------------------------------------------- Chapter 10 – Biology of Cancer/Tumor Spread TUMOR –​ Neoplasm (Neoplasia): cells look dysplastic; unusual sizes, unusual  shapes ​In situ vs. Invasive Neoplasm »​ In situ Neoplasm: skin cancer, skin abnormality; contained; hasn’t spread »​ Invasive Neoplasm: invades surrounding tissues; –​ Preceded by cellular dysplasia: cells that don’t look normal; abnormal dividing of cells ​Cells have a high(er) mitotic index »​ Mitotic Index: rate of the cells going through mitosis; how fast they spread; cell division –​ Benign vs. Malignant Tumor »​ Benign Tumor: noncancerous; does not spread; higher mitotic index than tissue it came from; better prognosis; hogs nutrition from body »​ Malignant Tumor: cancerous; spreads; higher mitotic index than benign ​Metastasis: fragmenting; travel through blood or lymph ​Extravasation: grow branches to spread ​Capsule: layer of tissue that keeps tumor contained; benign tumors ​Differentiate: cells go down a different metabolic pathway TUMOR- MANY TYPES –​ Carcinoma (Epithelial tissue-derived): most tumors ​Carcinoma in situ (CIS): skin cancer; tumor that is non-invasive –​ Adenocarcinoma (Gland/duct tissue-derived): can effect the rest of the body; hormone concentrations can be thrown off; hormones  being attacked can sometimes determine where cancer is –​ Sarcoma (Connective tissue-derived): bone- osteosarcoma –​ Lymphoma (Lymphatic tissue-derived): –​ Leukemia (Blood-forming tissue-derived): bone marrow; white bloods, red blood cells, platelets; mostly white blood cells affected; white blood cells are the only ones that can metabolize and have a nucleus; platelets are only fragments; red blood cells are not alive –​ Teratoma (Germ cell-derived): has teeth –​ Several others CLINICAL STAGING OF TUMORS –​ Zero – No evidence of tumor/cancer –​ Stage 1 – Confined to organ of origin –​ Stage 2 (B) – Locally invasive –​ Stage 3 (C) – Spread to “regional” structures –​ Stage 4 (D) – Spread to distant sites –​ The TNM System ​T = degree of tumor spread ​N = lymph node involvement ​M = presence of distant metastasis TUMOR MARKERS –​ Made (often in abnormally high amounts) by cancer cells –​ Found on cancer cell membranes/in body fluids; cell damage can indicate cancer; not all cell damage in cancerous  –​ Can be used clinically to… ​Screen high-risk individuals ​Diagnose tumors ​Follow treatment → provide prognosis GENETIC BASIS OF CANCER –​ Cancer prevalence increases with age! –​ The “Multi-Hit Hypothesis”: the longer the cell is around the more mutations accumulate; more mutations= greater likelihood of triggering certain cancers ​Older cells = more genetic mutations; induced mutation: DNA is exposed to a mutagen- substances that caused induce mutations; physical or chemical substance; spontaneous mutation- mistake in DNA replication; the older the cells are the more likely they are to replicate –​ Clonal Expansion (Clonal Proliferation) ​Cancer cells have a “competitive advantage”: cancer cells divides faster; have an advantage over normal cells IN CANCEROUS TUMORS –​ Cells exhibit autonomy: make their own rules; only care for their survival and proliferation at the expense of normal cells –​ “Inappropriate” autocrine signaling happens: happens in normal cells and in cancer cells; cancer cells do too much of it; send chemicals to each other; can communicate with each other; when cells send chemical messages to stimulate their own growth –​ Cells lose density-dependent inhibition: normal cells do this; cancer cells; when cells reach a certain density in a tissue they signal each other to stop dividing; cancer cells lose this and keep dividing regardless of density –​ Cells lose anchorage dependence: cells lose ability to do; common in malignant tumors; if cells are not connected to other cells like them they die; cells in tumors can keep growing and dividing; don’t need anymore; makes metastasis possible –​ Cells may “disable” apoptosis pathways: cancer cells lose ability to commit cellular suicide; just keep dividing; have to disengage apoptosis pathways in order to divide –​ Cells may use glycolysis products for growth: glycolysis- break down glucose for energy; cells take glucose and breakdown into pyruvic acid which gets sent down to electronic transport chain and make energy »​ The Warburg Effect: instead of breaking pyruvate down for energy, they break it down for amino acids, nucleotides so they can replicate and make more of their DNA; use it for molecules they need for growth; energy to do this comes from surrounding cells; steal energy from the body –​ Cells can secrete angiogenic factors: means to make blood vessels; tumors need a blood supply; tumors have blood vessels and are extensively vascularized –​ Cells often down-regulate fibronectin synthesis: protein that helps with tissue cohesion- keeps cells together in tissues; cancer cells turn  off; makes branching into other tissues you easier; makes you more “slippery”; if you turn down fibronectin cancer cells can “slip” or “branch” into other tissues ​ Cells may attain “immortality” »​ Often result of ↑ telomerase enzyme: over time telomeres get shorter and shorter causing cells to die and become replaced; cancer cells make them longer so they have a longer lifespan; good thing for cells to become replaced over time GENETIC BASIS OF CANCER –​ Oncogene (and Proto-Oncogene): when activated can cause the development of cancer –​ May be activated by… ​ Point Mutations ​ Chromosomal Alterations/Amplifications ​ Loss of Heterozygosity: ​ Gene Silencing (DNA Methylation): adding a methyl group to genes can cause; genes gets turned off at the wrong time can lead to development of cancer ​ External Pathogens ​ Inflammation-promoting chemicals (e.g. COX-2): can trigger the likelihood of cancer developing; chemicals produced in inflammatory response can increase the likelihood of tissue becoming cancerous; hep B & hep C can cause chronic inflammation in the liver, causing likelihood of cancer  –​ Are some families genetically prone to cancer? »​ Yes; certain gene mutations can increase the likelihood of cancer; Breast cancer: Brc1 and Brc2 genes; the genes you inherit cause this INTERNAL PROTECTION FROM CANCER –​ Tumor-Suppressor Genes (“antioncogenes”): ​ Negatively regulate cell growth ​ e.g. retinoblastoma gene – Rb: produces protein that suppresses tumor growth; protects us from cancer –​ Caretaker Genes ​ Repair damage to genes/chromosomes ​ MANY types –​ T-cells: can recognize & attack tumors; can detect specific antigen ​ Are often able to recognize cancerous cells METASTASIS –​ Spread to distant sites (via fragmentation) –​ Metastasis usually involves: cells that are no longer anchorage dependent ​ (1) Direct spread to adjacent tissues –​ Primary Tumor ​ (2) Penetration into blood/lymphatic systems ​ (3) Fragmentation into blood/lymph ​ (4) Transport to secondary sites: also called secondary tumor ​ (5) Entry, attachment, and growth in 2º sites –​ Organ Tropism: metastasis has preferences for where they spread to