Paramedic Care: Principles & Practice Volume 2: Paramedicine Fundamentals CHAPTER Fourth Edition...

Paramedic Care: Principles & Paramedic Care: Principles & PracticePractice

Volume 2: Paramedicine FundamentalsVolume 2: Paramedicine Fundamentals

CHAPTER

Fourth EditionFourth Edition

Pathophysiology

Multimedia Directory

Alveolar Gas Exchange AnimationSlide 183Understanding ARDS VideoSlide 195Phases of Hypovolemic Shock Animation

Standard

• Pathophysiology

Competency

• Integrates comprehensive knowledge of pathophysiology of major human systems.

Introduction

• Homeostasis: body maintains internal environment in steady state of balance.

• Disease: abnormal structural or functional change within body.

• Pathophysiology: study of disease.

Introduction

• Pathology: medical science that deals with all aspects of disease.

• Pathologist: physician who specializes in pathology.

Hierarchical Structure of the Body

• Cells: smallest unit of life made up of molecules (made up of atoms).

• Tissue: similar cells that perform common function.

• Organ: group of tissues working together to perform similar function.

• Organ system: group of organs working together to perform common or similar function.

• Organism: group of organ systems functioning together.

• Human being is organism with 11 different organ systems.

• Humans are social creatures.• Population: all the organisms of same species residing in distinct geographic area.

• Community: total of all living organisms occupying defined geographic area.

• Ecosystem: community and its physical environment.

• Biome: geographic area with similar climatic conditions.

• Biosphere: portion of Earth where life is found.

Part 1Disease

Disease

• Predisposing Factors to Disease– Age– Gender– Genetics– Lifestyle– Environment

Disease

• Risk Analysis– Cannot control genetics, gender, age.– Can control lifestyle and environment.

– Minimizing predisposing factors can slow effects of age.

– Data can be used to modify risk factors that can be modified.

– Risk analysis used to look at person's whole life.

Disease

• Disease– Pathogenesis: sequence of events that leads to development of disease.

– Idiopathic: predisposing factors cannot be identified.

– Etiology: occurrences, reasons, variables of a disease.

– Clinical presentation: manifestation of a disease.

Disease

• Disease– Symptom: what patient tells you about disease—subjective complaint.

– Sign: objective finding you identify through physical examination.

– Syndrome: specific constellation of signs and symptoms.

– Diagnosis: assumption disease will follow prescribed course.

Disease

• Disease– Acute: sudden onset.– Chronic (insidious): slower onset. – Complications: abnormalities that result from original problem.

– Sequelae: complications common or expected.

– Prognosis: expected outcome.

Disease

• Classifications of Disease– Infectious– Immunologic– Inflammatory– Ischemic– Metabolic– Nutritional– Genetic

Disease

• Classifications of Disease– Congenital– Neoplastic– Trauma– Physical agents– Iatrogenic– Idiopathic

Part 2Disease at the Chemical Level

Disease at the Chemical Level

• Big Bang theory: universe began with explosion of a primeval atom.

• Chemical evolution: simple chemicals present in primordial atmosphere and ocean combined to form larger, more complex chemicals.

• Led to formation of complex chemicals able to self-replicate.

• Marked transition from chemical evolution to biological evolution.

• Once biological evolution began, natural selection began.

• Self-replicating chemical surrounded by membrane; cellular life began.

• The Chemical Basis of Life– Atom: fundamental chemical unit.– Within atom are subatomic particles: electrons, protons, neutrons.

– Protons and neutrons: exist within nucleus of atom.

– Electrons: smaller particles; orbit nucleus.

• The Chemical Basis of Life– Element: substance that cannot be separated into simpler substances.

– Atomic number: number of protons in nucleus of atom defines element.

– Periodic table of elements: elements classified by their atomic number.

– Isotopes: elements have same number of protons; vary in number of neutrons.

A portion of the periodic table of elements. Each element has an atomic number (the number of protons), a mass number (the total number of neutrons and protons), and a one- or two-letter symbol. (Freeman, Scott, Biological Science, 4th Edition, © 2011. Reprinted and electronically reproduced by permission of Pearson Education, Inc., Upper Saddle River, NJ)

• The Chemical Basis of Life– Mass number: total number of neutrons and protons in atom.

– Radioactive isotopes: combinations of neutrons and protons make nucleus unstable.

– Radioactive decay: nuclei break down and emit radiation (alpha, beta, gamma rays) until atom regains stability.

• The Chemical Basis of Life– Half-life: time it takes for parent isotope to decrease by one-half.

– Orbital: specific shape; can hold two or more electrons.

– Electron shells: levels numbered starting with closest shell to nucleus.

• The Chemical Basis of Life– Valence shell: outermost shell of atom.

– Valence electrons: in valence shell.

– Noble gases: helium, neon, argon, krypton, xenon, radon.

• Chemical Bonding– Atoms become stable by bonding to other atoms.

– Covalent bond: equal sharing of electrons.

– Molecule: substance made up of atoms held together by covalent bonds.

– Ion: atom or molecule that acquired electrical charge.

• Chemical Bonding– Cation: atom or molecule with missing electrons and net positive charge.

– Anion: atom or molecule with extra electrons and net negative charge.

– Ionic bond: opposite charges attract; bonds form between atoms of opposite (positive/negative) charges.

• Chemical Bonding– Metallic elements: lose electrons.– Nonmetallic elements: gain electrons.

– Polar bond: unequal covalent bond; molecule is polar molecule.

– Hydrogen bond: attraction between slightly positively charged hydrogen atom and slightly negatively charged oxygen atom.

• Inorganic and Organic Chemicals– Inorganic: do not contain carbon. – Organic: do contain carbon (90% of all known chemicals).

– Major elements of living systems: Carbon (C) Hydrogen (H) Oxygen (O) Nitrogen (N)

• Inorganic and Organic Chemicals– Compound: chemical union of two or more elements.

– Major compounds of living systems: Carbohydrates Proteins Nucleic acids Lipids

• Classes of Biological Chemicals– Carbohydrates

Provide majority of calories in diets.

Divided into sugars; polysaccharides.

Monosaccharides: simple sugars.–Glucose, fructose, galactose.

Disaccharides: complex sugars.–Sucrose, lactose, maltose.

Polysaccharides: starches, cellulose, glycogen.

Starches: polymers of glucose.–Amylose, amylopectin.

Cellulose: most abundant organic molecule in the world; major structural material of plants.

Glycogen: important polysaccharide; stored in liver and skeletal muscle.

Glycogenolysis: controlled by hormones glucagon and epinephrine

• Classes of Biological Chemicals– Proteins

Nitrogen-based complex compounds; basic building blocks of cells.

Growth and repair of living tissues. Amino acids: smaller building blocks.

Peptide bonds: two amino acid molecules join and molecule of water released.

Protein Functions

Peptide: protein chain of less than 10 amino acids.

Polypeptide: chain of greater than 10 amino acids.

Levels of structure: primary, secondary, tertiary, quaternary.

Protein Structure

Enzymes: proteins; speed up chemical reactions.

Substrate binds to enzyme, forming enzyme-substrate complex.

Cofactors: nonprotein substances; aid in conversion of substrate to end product.

Coenzymes: organic cofactors.

• Classes of Biological Chemicals– Nucleic Acids

Deoxyribonucleic acid (DNA): contains genetic instructions for life.

Two long polymers (nucleotides) joined by paired substances (nucleobases).

Genetic code: four nucleobases and sequence of these encodes information.

DNA is a nucleic acid in which two chains of nucleotides twist around one another to form a double helix (spiral). The two chains are held together by hydrogen bonds between the nitrogen-containing bases. Each nucleotide of DNA contains the five-carbon sugar deoxyribose, a phosphate group, and one of four nitrogen-containing nucleobases: adenine (A), thymine (T), cystosine (C), and guanine (G). (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

Genes: code specific amino acid sequence; make up specific protein.

Number of chromosomes in cell nucleus varies with type of organism.

Ribonucleic acid (RNA): chemical similar to DNA; major role in protein synthesis.

Nucleotides: five-carbon sugar molecules.

Nitrogen bases: cadenine, cytosine, guanine, thymine uracil.

RNA and DNA Structural Differences

RNA is a single-stranded nucleic acid formed by the linking together of nucleotides composed of the five-carbon sugar ribose, a phosphate group, and one of four nitrogencontaining nucleobases: cystosine (C), adenine (A), guanine (G), and uracil (U). (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

Adenosine triphosphate (ATP): nucleotide; one of monomers of RNA.

Principal source of energy for most energy-utilizing activities of cells.

Phosphate bonds in ATP highly unstable.

• Classes of Biological Chemicals– Lipids

Chemicals that do not dissolve in water; nonpolar.

Function in long-term storage of biochemical energy, insulation, structure, control.

Triglycerides: rich sources of energy for body.

• Classes of Biological Chemicals– Lipids

Triglycerides: saturated or unsaturated.

Phospholipids: form membrane that surrounds cells.

Steroids: basic unit is cholesterol. Anabolism: constructive phase of metabolism.

Catabolism: destructive phase of metabolism.

• Classes of Biological Chemicals– Water

Universal solvent; polar molecule. Transports substances throughout body.

Helps to maintain constant body temperature.

Water is polar and participates in hydrogen bonds. (Freeman, Scott, Biological Science, 4th Edition, © 2011. Reprinted and electronically reproduced by permission of Pearson Education, Inc., Upper Saddle River, NJ)

• Acids and Bases– Dissociation reaction: compound or molecule breaks apart into separate components.

– Acids: substances that give up protons during chemical reactions.

– Bases: substances that acquire protons during chemical reactions.

– Acid-base reaction: transfer of protons.

• Acids and Bases– Water: ability to act as acid or base.

– Mole: molecular weight.– Logarithm: base number raised to certain power.

– pH scale: degree of acidity or basicity (alkalinity) of a substance.

The pH Scale and Hydrogen Ion Concentrations

• Acids and Bases– Buffer Systems

Counter body's normal production of acids; prevent variations in body's pH.

Buffer: substance dissolved in water that counteracts changes in pH.–Carbonic acid-bicarbonate buffer system

–Protein buffer system–Phosphate buffer system

Carbonic acid-bicarbonate buffer system: regulates pH of blood.

Buffer changes in pH caused by organic acids and fixed acids in extracellular fluid (ECF).

Can function only when respiratory system and control centers functioning normally.

Protein buffers depend on ability of amino acids in protein chain to react to changes in pH.

Hemoglobin buffer system helps to prevent changes in ECF pH when PaCO2 is rising or falling.

Phosphate buffer system limited in ECF; major role in stabilizing pH of urine.

– Acid-base balance tightly controlled. Excess hydrogen ions bind to water molecules; removed through exhalation of carbon dioxide from lungs or removed via kidneys.

• Acids and Bases– Change in pH occurs, buffer systems react fastest.

– Respiratory and renal systems help correct problem.

– Potassium levels and hydrogen ion levels major aspect of pH.

Maintenance of Acid-Base Balance

• Acid-Base Disorders– Any significant deviation of pH outside normal operating parameters (7.35–7.45).

– Two body systems: respiratory system and renal system.

pH as a Function of Metabolism and Respiration

• Acid-Base Disorders– Acidosis: excess of acids in body.– Alkalosis: excess of base in body.– Respiratory acid-base disorders: inequality in carbon dioxide generation in peripheral tissues and carbon dioxide elimination in respiratory system. Respiratory acidosis Respiratory alkalosis

• Acid-Base Disorders– Metabolic acid-base disorders: production of organic or fixed acids or conditions that affect levels of bicarbonate in ECF. Metabolic acidosis Metabolic alkalosis

• Acid-Base Disorders– Respiratory acidosis: respiratory system cannot eliminate all carbon dioxide generated through metabolic activities in peripheral tissues. Increase in PCO2; decrease in pH.

Hypercapnia: elevation in plasma CO2 level.

Decrease in respiratory rate, tidal volume, or combination of the two.

• Acid-Base Disorders– Respiratory alkalosis: respiratory system eliminates too much carbon dioxide through hyperventilation; hypocapnia.

– Hyperventilation: emotional situations, metabolic disorders, medical conditions, environmental factors, or combination.

• Acid-Base Disorders– Metabolic acidosis: deficiency of bicarbonate (HCO3

-) in body.

– Kidney: major role in maintaining stable pH levels.

– Metabolic alkalosis: uncommon; due to increase in HCO3

- levels or

decrease in circulating acids.

Part 3Disease at the Cellular Level

Disease at the Cellular Level

• The Cell– Basic unit of all living organisms.– Nucleus: central portion of cell. – Organelles: structures within nucleus that carry out biological processes.

– Prokaryotic cells: do not contain nucleus or organelles.

– Eukaryotic cells: contain nucleus and organelles.

Eukaryotic cells, such as the generalized animal cell shown here, have internal membrane-bound organelles. (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• The Plasma Membrane and Cytoplasm– Plasma membrane: consists of chemicals; phospholipids.

– Cell membrane: lipid bilayer.– Cytoplasm (cytosol): fills inside of cells; water, salts, organic molecules, enzymes that catalyze biochemical reactions.

• The Plasma Membrane and Cytoplasm– Intracellular fluid: water component of cytoplasm.

– Membrane proteins: Linkers Enzymes Receptors Transporters

• Plasma Membrane Functions– Cells adhere to each other or stick together; cell adhesion molecules (CAMs).

– Cell-cell recognition; ability of cell to distinguish one type of cell from another.

– Maintains structural integrity of cell.

Mechanism of Transport across the Plasma Membrane

• Plasma Membrane Functions– Role in communications between cells.

– Regulates movement of substances into and out of cell.

– Simple diffusion: random movement of molecules from region of higher concentration to region of lower concentration.

Simple diffusion is the random movement of molecules from a region of higher concentration to a region of lower concentration. Solutes diffuse across the membrane until equilibrium is reached on both sides.

• Plasma Membrane Functions– Rate of diffusion proportional to concentration gradient across membrane.

– Osmotic gradient: movement of water across semipermeable membrane.

– Osmosis: movement of water molecules from area of high water concentration to area of low water concentration.

• Plasma Membrane Functions– Free water: water free of solute.– Water: universal solvent.– Isotonic: concentrations of solutions on both sides of semipermeable membrane are equal.

– Hypertonic: solution on one side of membrane more concentrated than solution on other side.

• Plasma Membrane Functions– Hypotonic: solution on one side of membrane less concentrated than solution on other side.

– Osmosis generates pressure: osmotic pressure.

– Osmolarity: concentration of solute particles in solution.

• Plasma Membrane Functions– Facilitated diffusion: no expenditure of metabolic energy; transport assisted by integral proteins in plasma membrane. Carrier proteins Ion channels

• Plasma Membrane Functions– Active transport: cell moves solute across plasma membrane against concentration gradient. Carrier protein; energy in form of ATP.

– Sodium-potassium pump: transport of sodium ions out of cell and potassium ions into cell, against concentration gradient.

• Plasma Membrane Functions– Endocytosis: plasma membrane encircles substance to be ingested. When separated from cell membrane, vesicle released into cell.

– Phagocytosis: cell engulfs large particles or bacteria.

Phagocytosis. The cell engulfs large particles or bacteria. (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• Plasma Membrane Functions– Pinocytosis: cell engulfs droplets of fluid carrying dissolved substances.

– Exocytosis: large molecules leave cell by becoming encircled in membrane vesicle.

• The Cellular Environment: Fluids and Electrolytes– Severe derangements in fluid and electrolyte status can result in death.

– Water: most abundant substance in body (60%); total body water (TBW).

– Intracellular fluid (ICF): all fluid found inside body cells.

Body Fluid Compartments

• The Cellular Environment: Fluids and Electrolytes– Extracellular fluid (ECF): all fluid found outside body cells.

– Intravascular fluid: fluid found outside cells and within circulatory system.

– Interstitial fluid: all fluid found outside cell membranes; not within circulatory system.

• The Cellular Environment: Fluids and Electrolytes– Total body water and distribution vary with age and physiologic condition.

– Infant's TBW is 75 to 80% of body weight; 65% TBW average adult.

– Elderly, like very young, at high risk for dehydration and disorders related to electrolyte imbalances.

• The Cellular Environment: Fluids and Electrolytes– Intake: water coming into body.– Output: water excreted from body.– To maintain homeostasis, intake must equal output.

– Thirst regulates fluid intake.– Body maintains fluid balance by shifting water from one body space to another.

• The Cellular Environment: Fluids and Electrolytes– Dehydration: abnormal decrease in total body water. Gastrointestinal losses Increased insensible loss Increased sweating Internal losses Plasma losses

• The Cellular Environment: Fluids and Electrolytes– Fluid replacement based on fluid and electrolyte deficits.

– Dehydrated patient: dry mucous membranes, poor skin turgor, excessive thirst.

– Overhydration: edema; heart failure may be present.

• The Cellular Environment: Fluids and Electrolytes– Electrolytes: substances that dissociate into electrically charged particles when placed into water.

– Ions: charged particles.– Cations: ions with positive charge.– Anions: ions with negative charge.

• The Cellular Environment: Fluids and Electrolytes– Cations

Sodium (Na+) Potassium (K+) Calcium (Ca++) Magnesium (Mg++)

• The Cellular Environment: Fluids and Electrolytes– Anions

Chloride (Cl-) Bicarbonate Phosphate

– Electrolytes measured in milliequivalents per liter (mEq/L).

• The Cellular Environment: Fluids and Electrolytes– Body's fluid compartments separated by cell membranes.

– Semipermeable; selectively permeable.

– Compounds with small molecules (H2O) pass readily through membrane; larger compounds (proteins) restricted.

• The Cellular Environment: Fluids and Electrolytes– Movement of fluids through membrane enabled by pores in membrane.

– Electrolytes do not pass through membrane as readily as water due to their electrical charge.

– Water moves across cell membrane to dilute area of increased electrolyte concentration.

• The Cellular Environment: Fluids and Electrolytes– Movement of water more rapid than movement of electrolytes.

– Within extracellular compartment, movement of water between plasma in intravascular space and interstitial space function of forces in capillary beds.

• The Cellular Environment: Fluids and Electrolytes– Blood plasma generates oncotic force. – Hydrostatic pressure: blood pressure; force against vessel walls created by contractions of heart.

– Filtration: hydrostatic pressure forces some water out of plasma and across capillary wall into interstitial space.

• The Cellular Environment: Fluids and Electrolytes– Edema: accumulation of water in interstitial space. Decrease in plasma oncotic force Increase in hydrostatic pressure Increased capillary permeability Lymphatic channel obstruction

• The Cellular Environment: Fluids and Electrolytes– Edema: localized or generalized.– Sign of underlying disease or problem; edema itself causes problems.

– Antidiuretic hormone (ADH) or vasopressin: chief regulator of water retention and distribution.

• Intravenous Therapy– Introduction of fluids and other substances into venous side of circulatory system. Replace blood lost through hemorrhage.

Electrolyte or fluid replacement. Medications directly into vascular system.

• Intravenous Therapy– Blood: fluid of cardiovascular system.

– Transports nutrients, oxygen, hormones, heat.

– Plasma: liquid portion.– Blood cells: formed elements.

Red blood cells: erythrocytes. White blood cells: leukocytes. Platelets: thrombocytes.

• Intravenous Therapy– Erythrocytes: hemoglobin; transports oxygen; 99% of blood cells.

– Hemoglobin: iron-based compound that binds with oxygen.

– Leukocytes: responsible for immunity and fighting infection.

– Thrombocytes: major role in blood clotting.

Blood components.

• Intravenous Therapy– Plasma can be separated from formed elements by centrifugation.

– Hematocrit: percentage of blood occupied by erythrocytes.

– Most desirable fluid for blood loss replacement is whole blood.

Resuscitation Fluids

• Intravenous Therapy– Blood often fractionated (separated into parts); packed red blood cells used.

– Typed and cross-matched to prevent severe allergic reaction.

– Transfusion reactions: discrepancy between blood type of patient and blood type of blood being transfused.

• Intravenous Therapy– Intravenous fluids: colloids and crystalloids.

– Colloid: proteins; remain in intravascular space for extended period. Plasma protein fraction (Plasmanate) Salt-poor albumin Dextran Hetastarch (Hespan)

• Intravenous Therapy– Crystalloids: primary compounds used in prehospital intravenous fluid therapy. Isotonic solutions Hypertonic solutions Hypotonic solutions

– Intravenous replacement fluids: needs of patient; underlying problem.

• Intravenous Therapy– Most commonly used solutions in prehospital care: Lactated Ringer's solution. Normal saline (0.9% sodium chloride).

5% dextrose in water (D5W).

– Lactated Ringer's solution and normal saline used for fluid replacement.

• Organelles and Their Functions– Nucleus: largest organelle; contains cell's genetic information.

– Genetic information encoded by base sequences on DNA molecule.

– DNA controls cell functions and production of specific proteins.

– Genetic information on threadlike structures called chromosomes.

Diagram of the nucleus. (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• Organelles and Their Functions– Humans: 46 chromosomes (23 pairs).– Nuclear envelope: double membrane encases nucleus.

– Nucleoplasm: chromatin and materials inside nucleus.

– Nuclear pores: openings in nuclear envelope.

• Organelles and Their Functions– Nucleolus: region of DNA active in production of ribosomal RNA (rRNA).

– Ribosomes: synthesis of polypeptides and proteins.

– Endoplasmic reticulum: network of tubules, vesicles, sacs; interconnect with plasma membrane, nuclear envelope, other organelles in cell.

• Organelles and Their Functions– Rough endoplasmic reticulum (RER): contains ribosomes during protein synthesis.

– Smooth endoplasmic reticulum (SER): without ribosomes.

– Endoplasmic reticulum: role in replenishment and maintenance of plasma membrane.

The endoplasmic reticulum has rough and smooth portions. Rough endoplasmic reticulum (RER) has ribosomes attached during protein synthesis. Smooth endoplasmic reticulum (SER) has no attached ribosomes and serves various functions, depending on the cell type. (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• Organelles and Their Functions– Golgi apparatus (Golgi complex): processes proteins for cell membrane and other cell organelles.

– Lysosomes: “garbage disposal system” of cells. Break down foreign substances and invaders; degrade worn-out organelles.

Process macromolecule products.

• Organelles and Their Functions– Vacuoles: membrane-bound organelles used for temporary storage or transport of substances.

– Peroxisomes: generate and degrade hydrogen peroxide (H2O2); highly toxic to cells. Detoxify harmful substances; regulation of oxygen tension within cell.

• Organelles and Their Functions– Mitochondria: “powerhouses” of cells; provide energy needed for all of cell's biochemical processes.

– Cellular respiration.– Cristae: inner membrane folds form shelves within mitochondria.

• Cytoskeleton/Internal Cell Structures– Microtubules: long, hollow rods made of protein tubulin.

– Microfilaments: made from protein actin.

– Centrioles: cylindrical structures composed of groups of microtubules.

Mitochondria are sites of energy conversion in the cell. (Goodenough, Judith and Betty A. McGuire, Biology of Humans: Concepts, Applications, and Issues, 3rd Edition, © 2010. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• Cytoskeleton/Internal Cell Structures– Cytoskeleton: three-dimensional structure; serves as skeleton for cell.

– Cilia: hair-like structures that move in back-and-forth motion.

– Flagella: much longer than cilia; move in undulating, wavelike manner.

• Cellular Respiration/Energy Production– Digestive system breaks down nutrients: carbohydrates, proteins, lipids.

– Cellular respiration: aerobic; requires oxygen.

– Fermentation: anaerobic; does not require oxygen.

• Cellular Respiration/Energy Production– Oxidation: loss of electrons from one atom to another.

– Reduction: gain of electrons by one atom from another.

– Three biochemical processes glucose molecule must pass to produce energy through cellular respiration: glycolysis, citric acid cycle, electron transport.

• Cellular Respiration/Energy Production– Glycolysis

Occurs in cytoplasm; breakdown of six-carbon sugar glucose.

Energy-using and energy-yielding phases.

– Citric acid cycle (Kreb's cycle or tricarboxylic acid [TCA] cycle): Completely oxidizes remainder of glucose molecule.

• Cellular Respiration/Energy Production– Electron Transport Chain

Five types of carriers. Electrons transferred from one molecule to next; energy released.

Passed to oxygen; ultimate electron acceptor.

• Cellular Respiration/Energy Production– Fermentation

Breakdown of glucose without oxygen.

Final electron acceptor is pyruvate, not oxygen.

Very inefficient. Lactic acid fermentation. Alcohol fermentation.

• Cellular Response to Stress– Cellular adaptation: physiologic and structural changes to cell, in response to change or stress. Hyperplasia Hypertrophy Atrophy Metaplasia

• Cellular Response to Stress– Hyperplasia: increase in number of cells in tissue or organ. Hormonal hyperplasia: stimulation by hormones.

Compensatory hyperplasia: increase in tissue mass following tissue injury or loss.

Can be pathological.

• Cellular Response to Stress– Hypertrophy: increase in size of cells in tissue or organ. Due to creation of more structural components within cell.

Physiologic hypertrophy: increased physical demand.

Pathological hypertrophy: abnormal stress.

• Cellular Response to Stress– Atrophy: decrease in size of cell.

May be physiologic (effect of hormones) or pathological (result of disease or injury).

– Metaplasia: cell can change from one adult cell type to another adult cell type; reversible. Protects organism from stress.

Abnormal cell responses to stress include hypertrophy, hyperplasia, atrophy, metaplasia, and dysplasia.

• Cell Injury and Cell Death– Cells stressed to point they can no longer adapt, or exposed to toxic agents, cell injury results.

– Cell injury irreversible; cell death occurs.

– Irreversibly damaged cells undergo necrosis or apoptosis; normal process of keeping body healthy.

• Cell Injury and Cell Death– Ischemia: diminished blood flow.– Hypoxia: decreased availability of oxygen.

– Cellular respiration impaired; energy production limited to glycolysis.

• Cell Injury and Cell Death– Oxygen free radicals steal electrons from other compounds and generate new species of free radicals. Process can continue until components of cell are used up.

– Various chemicals, including drugs, can cause injury to a cell.

• Cell Injury and Cell Death– Apoptosis: cellular program activated; causes release of enzymes that destroy genetic material within nucleus of cell and selected proteins in cytoplasm. Can be physiologic or pathological.

– Dysplasia: abnormal or disordered growth in a cell. Precursor to development of cancer.

Part 4Disease at the Tissue Level

Disease at the Tissue Level

• Tissues– Tissue: group of cells that serve common purpose. Epithelial, connective, muscle, nervous.

– Histology: study of tissues.– Histopathology: study of abnormal or diseased tissue.

• Tissues– Germ layers: all tissues of the body derived from three cell lines in embryonic development.

– Endoderm: innermost germ cell layer; gives rise to epithelial tissue.

– Mesoderm: middle germ layer; gives rise to numerous body tissues.

• Tissues– Ectoderm: outermost germ layer; gives rise to all tissues that cover body surfaces as well as nervous system.

– Epithelium: derived from all three germ layers.

– Epithelial tissues: cover body surfaces.

• Tissues– Connective tissues: framework on which epithelial tissue rests and within which nerve and muscle tissue embedded.

– Muscle tissues: movement of substances through organism.

– Nerve tissues: coordinate activities of the body.

• Tissues– Epithelium forms barrier between organism and environment.

– Epithelial tissue covers external and internal body surfaces; lines passageways that communicate with outside.

• Tissues– Epithelial tissue:

Provides physical protection. Controls permeability. Provides special senses. Produces specialized secretions.

Types and locations of epithelial tissue. (Bledsoe, Bryan E.; Colbert, Bruce J.; Ankney, Jeff E., Essentials of Anatomy & Physiology for Emergency Care, 1st Ed., © 2011. Reprinted and electronically reproduced by permission of Pearson Education, Inc. Upper Saddle River, NJ)

• Tissues– Each type of epithelium has special purpose in organism.

– Simple epithelium: single cell layer thick; provides limited protection.

– Stratified epithelium: several layers thick; provides greater degree of protection.

• Tissues– Squamous epithelium: tissues with thin and flat cells.

– Cuboidal epithelium: cells cube-like or square shape.

– Columnar epithelium: cells tall and more slender.

Types of Epithelial Tissue

• Tissues– Connective tissues: deep tissues never exposed to external environment.

– Bind together; support tissues of body. Collagen fibers Elastic fibers Reticular fibers

• Tissues– Cell types in connective tissues

Fibroblasts Macrophages Adipocytes Mast cells

– Classes of connective tissue

• Tissues– Loose connective tissue

Adipose tissue– Dense connective tissue

Cartilage Bone Ligaments Tendons

• Tissues– Blood – Lymph

Types of Connective Tissue

• Tissues– Muscle tissues: specialized for contraction. Skeletal muscle Smooth muscle Cardiac muscle

Types of Muscle Tissue

• Tissues– Nervous tissue: found in brain, spinal cord, peripheral nerves. Conducts electrical impulses from one part of body to another; controls numerous body functions.

– Neurons: transmit electrical impulses.

– Neuroglia (glial cells): support, insulate, protect neurons.

Neuron.

• Neoplasia – Abnormal tissue growth; cells grow and multiply in uncontrolled fashion.

– Tumor: mass of uncontrolled cell growth.

– Primitive nonspecialized cells (stem cells) mature into specific cell types, depending on function.

• Neoplasia – Dysplastic (atypical) cells: develop abnormal growth patterns.

– Tumors benign or malignant.– Metastasis: malignant cells shed to other areas of body through bloodstream.

– Cancer locally invasive; recurrence common.

Abnormal cell development, progressing to invasive cancer.

• Neoplasia – Cancers: epithelial or connective tissue origin.

– Oncogenic factors: carcinogens and radiation.

– Oncogenic viruses: produce cancers.

– Genetics responsible for some cancers.

Tumor Origins and Names

Table 1–13 (continued) Tumor Origins and Names

• Neoplasia – Environment is risk factor.– Hormones play role in development of certain cancers.

– Carcinogenesis: process of developing a malignant neoplasia.

– Initiation: event begins transformation from normal tissue to cancer.

• Neoplasia – Promoter: carcinogen or any factor associated with cancer development. Necessary for continued development of tumor and speeds up process.

– Progression: malignancy exists and cells anaplastic in appearance. Followed by growth, local tissue invasion, possible metastasis.

• Neoplasia– Once cancer develops, it becomes invasive.

– Cancer spreads along tissue planes; attaches to various tissues.

– Spread of tumor cells makes treatment difficult; often causes death.

– Cancer cells graded by degree of cell differentiation present.

Part 5Disease at the Organ Level

Disease at the Organ Level

• Genetic and Other Causes of Disease– Inherited traits determined by deoxyribonucleic acid (DNA).

– Inherit genetic structure from parents.

– Every one of person's somatic cells contains 46 chromosomes.

– Sex cells contain 23 chromosomes.– 23 chromosomes from father; 23 chromosomes from mother.

• Genetic and Other Causes of Disease– Some diseases purely genetic.– Multifactorial disorders: diseases caused by combination of genetic and environmental factors.

– Clinical practitioners and epidemiologists study disease. Effects on individuals Effects on populations

• Diseases Involving Genetic and Other Risk Factors– Immunologic disorders– Cancer– Endocrine disorders– Hematologic disorders– Cardiovascular disorders

• Diseases Involving Genetic and Other Risk Factors– Renal disorders– Rheumatic disorders– Gastrointestinal disorders– Neuromuscular disorders– Psychiatric disorders

• Hypoperfusion– Hypoperfusion (shock): condition that is progressive and fatal if not corrected.

– All forms of shock have same underlying pathophysiology at cellular and tissue levels.

– Perfusion: constant, necessary passage of blood through body's tissues.

• Hypoperfusion– Inadequate perfusion of body tissues: hypoperfusion (shock).

– Perfusion dependent on functioning and intact circulatory system. The pump (heart) The fluid (blood) The container (blood vessels)

Components of the circulatory system.

• Hypoperfusion– Heart: pump of cardiovascular system.

– Factors affecting stroke volume: Preload Cardiac contractile force Afterload

– Preload: amount of blood delivered to heart during diastole.

• Hypoperfusion– Preload affects cardiac contractile force.

– Greater volume of preload, the more ventricles stretched.

– Catecholamines enhance cardiac contractile strength.

– Afterload: resistance against which ventricle must contract.

• Hypoperfusion– Cardiac output: amount of blood pumped by heart in 1 minute.

– Stroke volume × heart rate = cardiac output.

– Blood pressure: dependent on cardiac output; peripheral vascular resistance.

– Peripheral vascular resistance: pressure against which heart must pump.

• Hypoperfusion– Body strives to keep blood pressure constant by compensatory mechanisms and negative feedback loops.

– Blood: fluid of cardiovascular system; viscous fluid.

– Consists of plasma and formed elements (red cells, white cells, platelets).

• Hypoperfusion– Blood transports oxygen, carbon dioxide, nutrients, hormones, metabolic waste products, heat.

– Adequate amount of blood required for perfusion.

– Natriuretic peptides (NPs): long-term regulation of sodium and water balance, blood volume, arterial pressure.

• Hypoperfusion– Atrial natriuretic peptide (ANP); brain natriuretic peptide (BNP).

– Blood vessels (arteries, arterioles, capillaries, venules, veins) serve as container of cardiovascular system.

– Blood flow through vessels regulated by peripheral vascular resistance and pressure within system.

• Hypoperfusion– Oxygen brought into body via respiratory system.

– Oxygen from alveoli diffuses across alveolar-capillary membrane and into bloodstream.

– Red blood cells “pick up” this oxygen.

– Oxygen-enriched blood then circulates back to heart.

• Movement and Utilization of Oxygen (Fick principle)– Adequate inspired oxygen.– Appropriate movement of oxygen across alveolar-capillary membrane into arterial bloodstream.

– Adequate number of red blood cells.– Proper tissue perfusion.– Off-loading of oxygen at tissue level.

Alveolar Gas Exchange Animation

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• Hypoperfusion– Waste products of cellular metabolism carried away by blood.

– Carbon dioxide leaves bloodstream during oxygen-carbon dioxide exchange.

– Wastes expelled into lymphatic system.

– Wastes cleansed from blood by kidneys and excreted as urine.

Understanding ARDS Video

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• The Pathophysiology of Hypoperfusion– Inadequate pump– Inadequate fluid– Inadequate container

Underlying causes: infection, trauma and hemorrhage, loss of plasma through burns, severe cardiac arrhythmia, central nervous system dysfunction.

• The Pathophysiology of Hypoperfusion– Ultimate outcome of shock: impairment of cellular metabolism.

– Cells not receiving enough oxygen or are unable to use it effectively.

– Change from aerobic metabolism to anaerobic metabolism.

– Primary energy source for cells: glucose.

• The Pathophysiology of Hypoperfusion– Without oxygen, when glucose breakdown stops after glycolysis, cellular stores of ATP used up much faster than can be replaced; cellular metabolism gravely impaired.

– Sodium-potassium pumping mechanism fails.

– Cell membrane ruptures; cellular death soon follows.

• The Pathophysiology of Hypoperfusion– Same factors that reduce delivery of oxygen to cells reduce delivery of glucose to cells.

– Glucose prevented from entering cells remains in blood (hyperglycemia).

– Depletion of proteins in gluconeogenesis causes organ failure.

• The Pathophysiology of Hypoperfusion– Impaired use of oxygen and glucose leads to cellular death.

– Cellular death will lead to tissue death.

– Tissue death will lead to organ failure.

– Organ failure will lead to death of individual.

• The Pathophysiology of Hypoperfusion– Compensation: in shock, fall in cardiac output, detected as decrease in arterial blood pressure by baroreceptors, activates body systems that attempt to reestablish normal blood pressure.

– Renin-angiotensin system: aids body in maintaining adequate blood pressure.

• The Pathophysiology of Hypoperfusion– Compensated shock: to restore normal circulatory volume; if excessive bleeding managed and shock state has not progressed too far.

– Decompensated shock: if conditions causing shock too serious, or progress too rapidly, compensatory mechanisms may not be able to restore normal function.

• The Pathophysiology of Hypoperfusion– Irreversible shock: shock state may progress to condition where correction is no longer possible.

– Cardiac depression: critical factor in downward spiral of decompensation.

– Depression of vasomotor center of brain: consequence of reduced blood pressure.

• The Pathophysiology of Hypoperfusion– Metabolic wastes released into slower-flowing blood.

– Capillary cells suffer from lack of oxygen and nutrients, and acidosis.

– Cellular deterioration progresses to tissue deterioration, which progresses to organ failure.

• Types of Shock– Shock classified according to cause.– Cardiogenic shock: inability of heart to pump enough blood to supply all body parts. Most common cause of cardiogenic shock is severe left ventricular failure.

Presence of pulmonary edema, altered mentation, oliguria.

• Types of Shock– Hypovolemic shock: loss of intravascular fluid volume. Internal or external hemorrhage Traumatic injury; long bone or open fractures

Severe dehydration Plasma loss from burns Excessive sweating; diabetic ketoacidosis

Phases of Hypovolemic Shock Animation

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• Types of Shock– Hypovolemic shock:

“Classic” signs of shock. Mental status altered. Skin becomes pale. Blood pressure normal; then falls. Pulse rapid, slowing and disappearing.

Cardiac arrhythmias may develop.

• Types of Shock– Neurogenic shock: injury to either brain or spinal cord.

– Cause of neurogenic shock: central nervous system injury.

– Treatment same as for other types of shock: support of airway, oxygenation, ventilation, maintenance of body temperature, intravenous access.

• Types of Shock– Anaphylactic shock: severe allergic response; occurs very rapidly.

– Death can occur before patient can get to hospital; prompt intervention critical.

– Signs and symptoms can affect: skin, respiratory, cardiovascular, gastrointestinal, nervous systems.

– Treatment is pharmacological.

• Types of Shock– Septic shock: begins with septicemia (sepsis); infection enters bloodstream and is carried throughout body.

– Dysfunction of more than one organ system (multiple organ dysfunction syndrome).

– Signs and symptoms progressive; most susceptible: lungs, respiratory system.

• Multiple Organ Dysfunction Syndrome– MODS: progressive impairment of two or more organ systems resulting from uncontrolled inflammatory response to severe illness or injury.

– Sepsis and septic shock most common causes.

– Any severe disease/injury that triggers massive systemic inflammatory response.

• Multiple Organ Dysfunction Syndrome– Primary MODS: organ damage results from specific cause resulting from episode of shock, trauma, surgery.

– Secondary MODS: next time there is insult, primed cells activated, producing exaggerated inflammatory response.

– Inflammatory response enters self-perpetuating cycle.

• Multiple Organ Dysfunction Syndrome– Secondary insult triggers exaggerated neuroendocrine response.

– As result of release of inflammatory mediators and toxins and plasma protein cascades, a massive immune/ inflammatory and coagulation response develops.

• Multiple Organ Dysfunction Syndrome– Effects at cellular and tissue levels cause breakdown of organ systems.

– Does not occur in one intense crisis; develops over weeks.

– No specific therapy.– Early recognition; supportive measures.

Part 6The Body's Defenses Against

Disease and Injury

The Body's DefensesAgainst Disease and Injury

• Self-Defense Mechanisms– Infectious Agents

Bacteria Viruses Fungi Parasites Prions

• Infectious Agents– Bacteria

Single-cell organisms. Can reproduce independently; need host to supply food and other support.

Can be cultured and identified in hospital laboratories.

Categorized according to appearance; after staining with dyes (Gram stains).

Cause many common infections. Antibiotics kill or inhibit growth of bacteria.

Many bacteria release poisonous chemicals (toxins).

Exotoxins: proteins secreted and released by bacterial cell during growth.

Endotoxins: trigger inflammatory process and produce fever.

Septicemia (sepsis): systemic spread of toxins through bloodstream.

• Infectious Agents– Viruses

Cause most infections. Much smaller than bacteria; only seen with electron microscope.

Cannot grow without assistance of another organism.

Incapable of metabolism.

• Infectious Agents– Viruses

If does not find host cell, virus will die.

Do not produce toxins. Very difficult to treat. Cannot be treated with more than symptomatic care.

• Infectious Agents– Fungi (yeasts and molds): more like plants than animals. Rarely cause human disease other than minor skin infections.

Mycoses: fungus infections.

• Infectious Agents– Parasites

Protozoa to large intestinal worms. Treatment depends on organism and location.

– Prions Differ from viruses. Smaller; made entirely of proteins; do not have protective capsids.

• Three Lines of Defense– Anatomic barriers– Inflammatory response– Immune response

Three Lines of Defense Against Infection and Injury

Characteristics of the Inflammatory and Immune Responses

• The Immune Response– Detects antigens as foreign.– Produces antibodies that combine with antigens to control or destroy them.

– Immunity: long-term protection against specific foreign substances.

– Natural immunity not generated by immune response.

• The Immune Response– Natural immunity: inborn; part of genetic makeup of individual or species.

– Acquired immunity: develops as outcome of immune response.

– Active acquired immunity: generated by host's immune system after exposure to antigen; long-lasting.

• The Immune Response– Passive acquired immunity: transferred to person from outside source; temporary.

– Immunoglobulins: antibodies.– Primary immune response (initial): first exposure to antigen.

– Secondary immune response (anamnestic): second exposure.

• The Immune Response– Lymphocytes responsible for recognizing foreign antigens, producing antibodies, developing memory.

– B lymphocytes: do not attack antigens directly.

– Humoral immunity: long-term immunity to specific antigens.

• The Immune Response– T lymphocytes: do not produce antibodies.

– Cell-mediated immunity: recognize presence of foreign antigen; attack it directly.

– Lymphocytes: circulated through body as part of lymphatic system.

• Induction of the Immune Response– Immunogens: antigens that trigger immune response.

– Not every antigen is immunogen. Sufficient foreignness Sufficient size Sufficient complexity Presence in sufficient amounts

• Induction of the Immune Response– HLA antigens: body recognizes as self or foreign.

– Major histocompatibility complex (MHC): chromosome 6.

– Determines suitability (compatibility) of tissues and organs grafted or transplanted from donor.

• Induction of the Immune Response– Rh factor: Rh antigen D.– Incompatibility between Rh positive and Rh negative blood can cause harmful immune responses.

– ABO blood groups: two types of antigens may be present on surface of red blood cells; A and B.

• Induction of the Immune Response– Blood type A carries only A antigens.

– Blood type B carries only B antigens.

– Blood type AB carries both; universal recipient.

• Induction of the Immune Response– Blood type O carries neither; universal donor.

Blood Groups—ABO System

Compatibility among ABO Blood Groups

• Humoral Immune Response– Lymphocytes generated from stem cells in bone marrow.

– T lymphocytes: cell-mediated immunity.

– B lymphocytes: humoral immunity.– Specialization of B cells: processes of clonal diversity and clonal selection.

• Humoral Immune Response– Mature B cells produce memory cells.– All antibodies are immunoglobulins.– Structure of immunoglobulin molecules: Y-shaped chains.

– Antibody: direct or indirect effect on target antigen; inactivation or destruction of antigen.

• Humoral Immune Response– Direct Effects of Antibodies on Antigens Agglutination Precipitation Neutralization

– Indirect Effects of Antibodies on Antigens Enhancement of phagocytosis Activation of plasma proteins

• Humoral Immune Response– Antibodies serve four main functions: Neutralization of bacterial toxins.

Neutralization of viruses. Opsonization of bacteria. Activation of inflammatory processes.

• Humoral Immune Response– Classes of Immunoglobulins

IgM: largest immunoglobulin. IgG: “memory”; recognizes repeated

invasions of antigen. IgA: present in mucous membranes. IgE: least-concentrated immunoglobulin.

IgD: very low concentrations.

• Humoral Immune Response– Antigenic Determinants

Isotypic antigens: species-specific. Allotypic antigens: can differ between members of same species.

Idiotypic antigenic: can differ within same individual.

– Monoclonal antibody: produced in laboratory; pure and specific to single antigen.

• Humoral Immune Response– Secretory immune system (external or mucosal immune system): lymphoid tissues beneath mucosal endothelium. Protect body from pathogens inhaled or ingested.

• Cell-Mediated Immune Response– T cells do not produce antibodies. – Attack pathogens directly and create temporary immunity.

– Travel through thymus gland.– T cells become specialized: clonal diversity and clonal selection.

• Cell-Mediated Immune Response– Mature T Cells

Memory cells: secondary immune responses.

Td cells: transfer delayed hypersensitivity.

Tc cells: cytotoxic. Th cells: helper cells. Ts cells: suppressor cells.

• Cellular Interactions/Immune Response– Immune and inflammatory responses are interacting, not separate.

– Antigen-presenting cells (macrophages) interact with Th (helper) cells.

– Th (helper) cells interact with B cells.

– Th (helper) cells interact with Tc (cytotoxic) cells.

• Cellular Interactions/Immune Response– Cytokines: proteins produced by white blood cells; “messengers” of immune response.

– Monokine: cytokine released by macrophage.

– Lymphokine: cytokine released by a lymphocyte (T cell or B cell).

• Cellular Interactions/Immune Response– Sequence of processes necessary before immune response can begin: Antigen processing (by macrophages).

Antigen presentation (by macrophages).

Antigen recognition (by T cells or B cells).

• Cellular Interactions/Immune Response– Antigen processing: ingestion of invading organism; breakdown of its antigens.

– Antigen-presenting cells (APCs). T cell receptor (TCR): antigen-specific.

CD4 or CD8 receptors: respond no matter what antigen presented.

• Cellular Interactions/Immune Response– T cells and B cells not differentiated until antigens in system react with appropriate receptors on cell surfaces.

– Ts (suppressor) cells help suppress immune responses.

• Fetal and Neonatal Immune Function– To protect child in utero and during first months after birth, maternal antibodies cross placenta into fetal circulation.

– As immune system matures, levels of immunoglobulin begin to rise.

• Aging and the Immune Response– As human body ages, immune function begins to deteriorate.

– Primary assault on T cell function.

– Men and women over age 60 have decreased hypersensitivity responses; decreased T cell response to infections.

• Inflammation– Body's response to cellular injury.

– Immune response develops slowly; inflammation develops swiftly.

– Immune response specific; inflammation nonspecific.

– Immune response long-lasting; inflammation temporary.

• Inflammation– Immune response: one type of white blood cell (lymphocytes); inflammation: platelets and white blood cells.

– Immune response: one type of plasma protein (antibodies); inflammation: several plasma protein systems.

– Immune response and inflammation interdependent.

• Inflammation– Inflammation/immune response both considered part of immune system.

– Phases of inflammation: Phase 1: Acute inflammation Phase 2: Chronic inflammation Phase 3: Granuloma formation Phase 4: Healing

• Inflammation– Four Functions of Inflammation

Destroy and remove unwanted substances

Wall off infected and inflamed area

Stimulate immune response Promote healing

• Inflammation– Acute inflammation: triggered by any injury (lethal/nonlethal) to body's cells.

– Blood vessels contract and dilate. – Vascular permeability increases.– White cells and plasma proteins destroy invader and heal injury site.

• Inflammation– Mast cells activate inflammatory response through degranulation and synthesis.

– Degranulation: mast cells empty granules from their interior into extracellular environment. Physical injury, chemical agents, immunologic and direct processes.

The inflammatory response.

• Inflammation– Histamine: vasoactive amine (organic compound) released during degranulation of mast cells.

– Chemotactic factors: chemicals that attract white cells to site of inflammation.

– Chemotaxis: attraction of white cells.

Mast cell degranulation and synthesis.

• Inflammation– When stimulated, mast cells synthesize: leukotrienes and prostaglandins.

– Leukotrienes: slow-reacting substances of anaphylaxis (SRS-A); actions similar to histamines.

– Prostaglandins: increased vasodilation, vascular permeability, chemotaxis; cause pain.

• Plasma Protein Systems– Plasma proteins: proteins present in blood.

– Immunoglobulins (antibodies): key factors in immune response.

– Plasma protein systems critical to inflammation: complement system, coagulation system, kinin system.

• Plasma Protein Systems– Cascade: first action stimulated; that action causes next action, which causes next action until final action completed.

– Complement proteins lie inactive in blood until activated.

– Take part in almost all events of inflammatory response.

– Classic and alternative pathways.

• Plasma Protein Systems– Classic pathway: activated by formation of antigen-antibody complex during immune response.

– Alternative pathway: begins without development of antigen-antibody complex. Much faster than classic pathway; acts as part of first line of inflammatory defense.

• Plasma Protein Systems– Coagulation system (clotting): forms network at site of inflammation. Composed of protein called fibrin. Fibrinous network stops spread of infectious agents and products of inflammation.

Forms clot that stops bleeding.

• Plasma Protein Systems– Extrinsic pathway of coagulation: injury to vascular wall or surrounding tissues.

– Intrinsic pathway of coagulation: exposure to elements in blood itself.

– Continue toward same end product: fibrin.

• Plasma Protein Systems– Kinin system: chief product, bradykinin.

– Vasodilation, extravascular smooth muscle contraction, increased permeability, chemotaxis.

– Plasma kinin cascade: triggered by factors associated with coagulation cascade.

• Plasma Protein Systems– Control of plasma protein systems:

Inflammatory response essential for protection of body from unwanted invaders.–Functioning must be guaranteed.

Inflammatory processes powerful; potentially very damaging to body.–Must be controlled and confined to site of injury or infection.

• Plasma Protein Systems– Most inflammatory processes interact.

– Substance or action that activates one element tends to activate others.

– Inflammatory processes have to be both reliably started and stopped.

• Cellular Components of Inflammation– Exudate: collective term for all helpful substances.

– Sequence of events in inflammation Vascular response Increased permeability Exudation of white cells

• Cellular Components of Inflammation– Granulocytes: appearance of bag of granules; multiple nuclei. Neutrophils, eosinophils, basophils.

– Monocytes: single nucleus; change and mature when involved in inflammation. Become macrophages.

Types of White Blood Cells (Leukocytes)

• Cellular Components of Inflammation– All granulocytes and monocytes are phagocytes; blood cells that ingest other cells and substances.

– Neutrophils: first phagocytes to reach inflamed site.

– Eosinophils: primary defense against parasites.

• Cellular Components of Inflammation– Basophils: function within blood as mast cells do outside blood. Release histamines and chemicals that control constriction and dilation of vessels.

– Platelets: act with components of coagulation cascade to promote blood clotting.

• Cellular Products– Lymphokines: cytokines produced by lymphocytes. Stimulate monocytes to develop into macrophages; critical phase of inflammatory response.

– Monokines: cytokines produced by macrophages and monocytes.

• Cellular Products– Interleukin-1: lymphocyte-stimulating factor.

– Interferon: cytokine critical in body's defense against viral infection.

• Systemic Responses of Acute Inflammation– Fever, leukocytosis, increase in circulating plasma proteins.

– Fever: increase in temperature can create environment inhospitable to invading microorganisms.

– Fever: increases susceptibility of infected person to effects of endotoxins.

• Chronic Inflammatory Responses– Chronic inflammation: inflammation that lasts longer than two weeks.

– Caused by foreign object or substance that persists in wound.

– May accompany persistent bacterial infection.

– Prolonged by presence of chemicals and other irritants.

• Chronic Inflammatory Responses– Large numbers of cells degranulate and die.

– Infiltrate tissues; sometimes forming cavity that contains dead cells, dead tissue, tissue fluid (pus).

– Granuloma: walls off infection.– Tissue repair and scar formation final stages of inflammation.

• Local Inflammatory Responses– Vascular changes and exudation.– Exudate has three functions:

To dilute toxins released by bacteria and toxic products of dying cells

To bring plasma proteins and leukocytes to site to attack invaders

To carry away products of inflammation

• Resolution and Repair– Resolution: complete restoration of normal structure and function.

– Regeneration: proliferation of remaining cells.

– If resolution not possible, repair takes place, with scarring being end result.

• Resolution and Repair– Debridement: phagocytosis of dead cells and debris; dissolution of fibrin cells (scabs).

– Primary intention: minor wounds.– Secondary intention: extensive wounds.

– Reconstruction: initial wound response, granulation, epithelialization, contraction.

• Resolution and Repair– First step of healing: sealing off of wound by clot (scab).

– Repair begins with granulation.– Epithelial cells move in under scab, separating it from wound surface. Provides protective covering for healing wound.

• Resolution and Repair– Six to 12 days after injury, contraction begins as wound edges begin to move inward.

– Maturation: scar tissue remodeled; blood vessels disappear, leaving avascular scar; scar tissue becomes stronger.

• Resolution and Repair– Dysfunctional healing: insufficient repair, excessive repair, new infection. Causes: diabetes, hypoxemia, nutritional deficiencies, certain drugs.

Positioning, exercises, surgery, drugs can sometimes help to prevent or correct dysfunctional wound healing.

• Age and Mechanisms of Self-Defense– Newborns and elderly particularly susceptible to problems of insufficient immune and inflammatory responses.

• Variances in Immunity/Inflammation– Hypersensitivity: exaggerated and harmful immune response. Allergy: exaggerated immune response to environmental antigen.

Autoimmunity: disturbance in body's normal tolerance for self-antigens.

Isoimmunity (alloimmunity): immune reaction between members of same species.

• Variances in Immunity/Inflammation– Original insult (exposure to antigen).– Genetic makeup; determines susceptibility to insult.

– Immunologic process that boosts response beyond normal bounds.

– Immediate hypersensitivity reactions.– Delayed hypersensitivity reactions.

• Variances in Immunity/Inflammation– Mechanisms of Hypersensitivity Reaction Type I: IgE-mediated allergen reactions

Type II: tissue-specific reactions Type III: immune-complex-mediated reactions

Type IV: cell-mediated reactions

• Variances in Immunity/Inflammation– H1 receptors on target cells promote inflammation when contacted by histamine.

– H2 receptors inhibit inflammation when contacted by histamine.

• Clinical Indications of IgE-Mediated Responses– Skin: flushing, itching, urticaria, edema

– Respiratory system: breathing difficulty, laryngeal edema, laryngospasm, bronchospasm

– Cardiovascular system: vasodilation and permeability, increased heart rate, increased blood pressure

• Clinical Indications of IgE-Mediated Responses– Gastrointestinal system: nausea, vomiting, cramping, diarrhea

– Nervous system: dizziness, headache, convulsions, tearing

• Variances in Immunity/Inflammation– Anaphylactic reactions are life threatening.

– Tissue-specific antigens: exist on the cells of only some body tissues.

– Four mechanisms by which Type II tissue-specific reactions attack cells.

• Variances in Immunity/Inflammation– Type III immune-complex-mediated reactions: antigen-antibody formed when antibody in blood or suspended in body secretions meets and binds to specific antigen.

– Systemic and/or localized.

• Variances in Immunity/Inflammation– Type IV reactions: activated directly by T cells; do not involve antibody.

– Lymphokine-producing T cells (Td cells); cytotoxic T cells (Tc cells).

• Variances in Immunity/Inflammation– Hypersensitivity/Targeted Antigen

Allergy/environmental antigens Autoimmunity/self-antigens Isoimmunity/other person's antigens

– Allergens: antigens that are targets of allergic reaction.

• Variances in Immunity/Inflammation– Autoimmunity: breakdown in body's tolerance for self-antigens; immune system attacks body's own cells.

– Isoimmunity: one member of species has immune reaction to cells from another member of the same species.

• Autoimmune and Isoimmune Diseases– Graves' disease– Rheumatoid arthritis– Myasthenia gravis– Immune thrombocytopenic purpura– Isoimmune neutropenia– Systemic lupus erythematosus (SLE); lupus

– Rh and ABO isoimmunization

• Deficiencies: Immunity/Inflammation– Congenital (primary) immune deficiency develops if development of lymphocytes in fetus or embryo is impaired or halted.

– Acquired (secondary) immune deficiencies develop after birth; do not result from genetic factors.

• Deficiencies: Immunity/Inflammation– Nutritional deficiencies– Iatrogenic deficiencies– Deficiencies caused by trauma– Deficiencies caused by stress– Acquired immunodeficiency syndrome (AIDS)

– Human immunodeficiency virus (HIV)

• Deficiencies: Immunity/Inflammation– Replacement Therapies

Gamma globulin therapy Transplantation and transfusion Gene therapy

• Stress and Disease– Stress: state of physical and/or psychological arousal to a stimulus.

– Stressor: stimulus/cause.– General adaptation syndrome (GAS)

Stage I: Alarm Stage II: Resistance, or adaptation Stage III: Exhaustion

• Stress and Disease– Physiologic stress: chemical or physical disturbance in cells or tissue fluid produced by a change; requires response to counteract disturbance. Stressor that initiates disturbance. Chemical or physical disturbance stressor produces.

Body's counteracting response.

• Stress Responses– Stress response: initiated by a stressor.

– Hormones released in response to stress Catecholamines (norepinephrine and epinephrine)

Cortisol Beta endorphins Growth hormone Prolactin

The stress response: effects on the sympathetic nervous, endocrine, and immune systems.

• Stress Responses– Effects of catecholamines prepare body for “fight-or-flight” in response to stressor.

Physiologic Effects of Catecholamines

Physiologic Effects of Catecholamines (continued)

Physiologic Effects of Cortisol

• Stress Responses– Complex interaction among nervous, endocrine, and immune systems.

Stress- and Immune-Related Diseases and Conditions

Stress- and Immune-Related Diseases and Conditions (continued)

• Stress, Coping, and Illness Interrelationships– Physiologic stress: caused by events that directly affect body.

– Psychological stress: unpleasant emotions caused by life events.

– Those who cope positively with stress have reduced chance of becoming ill; those who don't have greater chance of becoming ill.

Summary

• Cell: basic unit of life. – Contains all components to turn nutrients into energy, remove waste products, reproduce, carry on other essential life functions.

• Body's cells interact via electrochemical substances: hormones, neurotransmitters, neuropeptides, cytokines.

Summary

• Cells exist in fluids and electrolytes.

• When something interferes with normal cell function, cell environment, or cell intercommunication, disease can begin or advance.

• Groups of cells that perform similar functions form tissues.

• Group of tissues functioning together is an organ.

Summary

• Group of organs that work together is an organ system.

• Perfusion of tissues necessary to provide essential nutrients to cells and to remove wastes.

• Inadequate perfusion: hypoperfusion or shock.

Summary

• If shock not corrected, creates downward spiral toward irreversible shock, possible multiple organ dysfunction syndrome (MODS), death.

• Cells injured: hypoxia, chemicals, infectious agents, immunologic/ inflammatory injuries.

• Diseases: genetic or environmental factors; combination of factors.

Summary

• Homeostasis: body's normal dynamic steady state.

• Cells adapt through atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia.

• Negative feedback mechanisms work to correct, or compensate for, shock.

• Body's chief means of self-defense is immune system.

Summary

• Immune and inflammatory responses: attack and destroy infectious agents.

• Immune response system: hypersensitivity reactions; immune deficiency disorders.

• Stress can also contribute to disease.

Paramedic Care: Principles & Practice Volume 2: Paramedicine Fundamentals CHAPTER Fourth Edition...

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