Pathophysiology IIIPathophysiology III

Paramedic Class 108Paramedic Class 108

Disease in the Human BodyDisease in the Human BodyFactorsFactors

Disease in the Human BodyDisease in the Human BodyFactorsFactors

GeneticsGenetics

EnvironmentEnvironment

Life-styleLife-style

AgeAge

GenderGender

GeneticsGenetics

EnvironmentEnvironment

Life-styleLife-style

AgeAge

GenderGender

Many Factors Combine To Cause Many Factors Combine To Cause DiseaseDisease

Inherited traits are determined by molecules Inherited traits are determined by molecules

of deoxyribonucleic acid (DNA).of deoxyribonucleic acid (DNA).

Each somatic cell contains 46 Each somatic cell contains 46

chromosomes.chromosomes.

Sex cells contain 23 chromosomes.Sex cells contain 23 chromosomes.

Many Factors Combine To Cause Many Factors Combine To Cause DiseaseDisease

An offspring receives 23 chromosomes from the An offspring receives 23 chromosomes from the mother and 23 chromosomes from the father.mother and 23 chromosomes from the father.

One or more chromosomes may be abnormal One or more chromosomes may be abnormal and may cause a congenital disease or a and may cause a congenital disease or a propensity toward acquiring a disease later in propensity toward acquiring a disease later in life.life.

Genetic vs. EnvironmentalGenetic vs. Environmental

Genes need an environment to work.Genes need an environment to work.

Environmental factors vary with everyone.Environmental factors vary with everyone.

Environment the same – People have Environment the same – People have different genetic characteristics.different genetic characteristics.

Very ComplexVery Complex

Genetic FactorsGenetic Factors

Heredity – Chromosomes Heredity – Chromosomes

Individual Genetic FactorsIndividual Genetic Factors

Entire Chromosmal abnormalitiesEntire Chromosmal abnormalities

Genetic FactorsGenetic Factors

EXAMPLESEXAMPLES

Down’s Syndrome – Rearranged Down’s Syndrome – Rearranged Chromosomes.Chromosomes.

Sickle Cell / Hemophilia – Single gene on Sickle Cell / Hemophilia – Single gene on chromosome passed on results in an chromosome passed on results in an abnormal protein.abnormal protein.

EXAMPLESEXAMPLES

Down’s Syndrome – Rearranged Down’s Syndrome – Rearranged Chromosomes.Chromosomes.

Sickle Cell / Hemophilia – Single gene on Sickle Cell / Hemophilia – Single gene on chromosome passed on results in an chromosome passed on results in an abnormal protein.abnormal protein.

Genetic FactorsGenetic Factors

PolygenicPolygenic

Determined by many genes Determined by many genes

multi- factionalmulti- factional

CADCAD

HTNHTN

CA CA

PolygenicPolygenic

Determined by many genes Determined by many genes

multi- factionalmulti- factional

CADCAD

HTNHTN

CA CA

Environmental FactorsEnvironmental FactorsEnvironmental FactorsEnvironmental Factors

Think Chronic Disease’sThink Chronic Disease’s

Microorganism & immunological exposureMicroorganism & immunological exposure

Personal HabitsPersonal Habits

Chemical SubstancesChemical Substances

Physical EnvironmentsPhysical Environments

Psychosocial EnvironmentsPsychosocial Environments

Environment & HeredityEnvironment & Heredity

More than one genetic defectMore than one genetic defect

CADCAD

HTNHTN

CA > 40 yoaCA > 40 yoa

AGE & GENDERAGE & GENDERCumulative EffectsCumulative Effects

Gender SpecificGender Specific

Breast CancerBreast Cancer

Testicular CancerTesticular Cancer

Ovarian CancerOvarian Cancer

Prostrate CancerProstrate Cancer

Gender SpecificGender Specific

Breast CancerBreast Cancer

Testicular CancerTesticular Cancer

Ovarian CancerOvarian Cancer

Prostrate CancerProstrate Cancer

AGE & GENDERAGE & GENDERCumulative EffectsCumulative EffectsAGE & GENDERAGE & GENDER

Cumulative EffectsCumulative Effects

ENVIRONMENTAL ENVIRONMENTAL

Cigarette SmokingCigarette Smoking

Lung CancerLung Cancer

CAD – MenCAD – Men

ENVIRONMENTAL ENVIRONMENTAL

Cigarette SmokingCigarette Smoking

Lung CancerLung Cancer

CAD – MenCAD – Men

COMBINED EFFECTSCOMBINED EFFECTS

Familial Disease TendenciesFamilial Disease Tendencies

Aging and Age related DisordersAging and Age related Disorders

Familial Disease TendenciesFamilial Disease Tendencies

Aging and Age related DisordersAging and Age related Disorders

LINES OF DEFENSELINES OF DEFENSE

CharacteristicsCharacteristics

Body’s Self-Defense MechanismsBody’s Self-Defense Mechanisms

Defense against illness and injuryDefense against illness and injury– First-line external barriers include:First-line external barriers include:

SkinSkin

Mucous membranes of the respiratory, digestive, Mucous membranes of the respiratory, digestive, and genitourinary (GU) tractand genitourinary (GU) tract

– Second—Inflammatory responseSecond—Inflammatory response– Third—Immune responseThird—Immune response

Stages of Inflammatory ResponseStages of Inflammatory Response

Cellular response to injuryCellular response to injury– Energy depletion, autolysisEnergy depletion, autolysis

Vascular response to injuryVascular response to injury– Hyperemia, vessel dilationHyperemia, vessel dilation– Leukocyte migrationLeukocyte migration

PhagocytosisPhagocytosis– Leukocytes destroy pathogensLeukocytes destroy pathogens– Exudate (pus) formsExudate (pus) forms

Cellular ResponseCellular ResponseMetabolicMetabolic

Decreased Energy Stores (Aerobic Respiration) Decreased Energy Stores (Aerobic Respiration)

Sodium/Potassium Pump impairedSodium/Potassium Pump impaired

Cell Swelling – AcidosisCell Swelling – Acidosis

Membranes LeakMembranes Leak

Cellular DestructionCellular Destruction

Inflammatory ResponseInflammatory Response

Vascular ResponseVascular Response

Dilation - arterial, venules, and capillaries.Dilation - arterial, venules, and capillaries.

Increase permeability (Interstitial = Increase permeability (Interstitial = Edema)Edema)

Leukocytes –Leukocytes – Attack injured TissueAttack injured Tissue

PhagocytosisPhagocytosis

Leukocytes – attack & DestroyLeukocytes – attack & DestroyMacrophages – Clean area of dead cellsMacrophages – Clean area of dead cellsOccurs at site of invasionOccurs at site of invasionGeneral Circulation – SystemicGeneral Circulation – SystemicLeukocytes – LysesLeukocytes – LysesPus Forms – (Exudate)Pus Forms – (Exudate)Pus= dead dying leukocytes, broken down Pus= dead dying leukocytes, broken down tissue cells,pathogens,and tissue fluid.tissue cells,pathogens,and tissue fluid.

MAST CELLSMAST CELLSConnective TissueConnective Tissue

CytoplasmCytoplasm Histamine/serotoninHistamine/serotonin

– AllergiesAllergies

– Vasoactive aminesVasoactive amines– Aminos Aminos – AllergiesAllergies

– Chemotactic FactorsChemotactic Factors– Random migrationRandom migration

– Stimulated migrationStimulated migration

– Attracts leukocytes Attracts leukocytes

MAST DEGRANULATIONMAST DEGRANULATION

Stimulated by physical Injury – Chemicals – Allergies IgEStimulated by physical Injury – Chemicals – Allergies IgE

Histamine – Capillary DilationHistamine – Capillary Dilation

Serotonin – Vasoconstriction or dilationSerotonin – Vasoconstriction or dilation

Chemotaxis – Attract White Blood CellsChemotaxis – Attract White Blood Cells

Neutrophils – Most PrevalentNeutrophils – Most Prevalent

Eosinphils – parasites - Worms Eosinphils – parasites - Worms

MAST CELL HELPMAST CELL HELP

Mast Cell Degradation and Synthesis

Inflammatory ResponseInflammatory ResponseLocalLocal

1.1. VascularVascular

2.2. Vasodilatation increased permeabilityVasodilatation increased permeability

3.3. Formation of pus (Exudate)Formation of pus (Exudate)

4.4. Local Signs - ???Local Signs - ???

5.5. Heat, Redness, swelling, pain and tenderness Heat, Redness, swelling, pain and tenderness

Inflammatory ResponseInflammatory ResponseSystemicSystemic

Fever ( Pyrogens)Fever ( Pyrogens)

LeukocytesLeukocytes

Increased Plasma ProteinsIncreased Plasma Proteins

Fever ( Pyrogens)Fever ( Pyrogens)

LeukocytesLeukocytes

Increased Plasma ProteinsIncreased Plasma Proteins

Inflammatory ResponseInflammatory ResponseInflammatory ResponseInflammatory Response

Acute inflammationAcute inflammation– Local responsesLocal responses– Systemic responsesSystemic responses

Chronic inflammationChronic inflammation– Inflammation Inflammation >> 2 wks 2 wks

Inflammatory ResponseInflammatory ResponseChronicChronicDefinedDefined

Lasting 2 weeks or longerLasting 2 weeks or longer

Results FromResults From Unsuccessful acute inflammationUnsuccessful acute inflammation

Persistent –Ongoing antigen or infectionPersistent –Ongoing antigen or infection

DefinedDefined

Lasting 2 weeks or longerLasting 2 weeks or longer

Results FromResults From Unsuccessful acute inflammationUnsuccessful acute inflammation

Persistent –Ongoing antigen or infectionPersistent –Ongoing antigen or infection

CHRONIC INFLAMMATIONCHRONIC INFLAMMATIONCharacteristicsCharacteristics

Persistent – Acute Inflammation Response

Neutrophil- Degranulation & Death

Lymphocyte Activation – Clean up

Fibroblast Activation - Healing

Infiltration (pus) – Clean up

Tissue Repair (Scar)

Types of ImmunityTypes of ImmunityTypes of ImmunityTypes of Immunity

Natural (native) Genetic or InnateNatural (native) Genetic or Innate– Present at BirthPresent at Birth

– No prior exposureNo prior exposure

AcquiredAcquiredHumoral immunityHumoral immunity

Cell-mediated immunityCell-mediated immunity

Acquired ImmunityAcquired Immunity

Active-Active- Immunizations or disease (Natural) Immunizations or disease (Natural)

Passive –Passive – Mother –Child or Antibody Mother –Child or Antibody

administration. administration.

Humoral vs. Cell ImmunityHumoral vs. Cell Immunity

Humoral – (Anti Body Mediated)Humoral – (Anti Body Mediated)

Lymphocyte B cellsLymphocyte B cells

Cell Mediated ( cellular immunity)Cell Mediated ( cellular immunity)

Lymphocyte T cellsLymphocyte T cells

Direct Attack – Best DefenseDirect Attack – Best Defense

AGE & IMMUNE AGE & IMMUNE RESPONSERESPONSE

INFANTSINFANTSAntibodies – Passive ImmunityAntibodies – Passive Immunity

Older we get the less immunities Older we get the less immunities we maintain.we maintain.

But Why? But Why?

Induction of Immune Response Induction of Immune Response TriggersTriggers

AntigenAntigen– Reacts with preformed components of Reacts with preformed components of

immune system immune system

ImmunogenImmunogen– Antigen that can also induce formation of Antigen that can also induce formation of

antibodiesantibodies

Induction of Immune ResponseInduction of Immune Response

To be immunogenic, the antigenic molecule To be immunogenic, the antigenic molecule must bemust be– Sufficiently foreign to the hostSufficiently foreign to the host– Sufficiently largeSufficiently large– Sufficiently complexSufficiently complex– Present in sufficient amountsPresent in sufficient amounts

B lymphocytes - AntibodiesB lymphocytes - Antibodies

T lymphocytes - KillersT lymphocytes - Killers

IMMUNE RESPONSEIMMUNE RESPONSE

Summary of the

Immune response

Immune Immune vs.vs. Inflammatory Inflammatory

ImmuneImmune InflammationInflammation

Develops slowlyDevelops slowly Develops swiftlyDevelops swiftly

Targets specific antigensTargets specific antigens Non-specificNon-specific

Long-lasting—has “memory”Long-lasting—has “memory” Temporary—days to weeksTemporary—days to weeks

Involves one type of white Involves one type of white blood cellblood cell

Involves many types of Involves many types of white blood cells and white blood cells and plateletsplatelets

One type of plasma protein—One type of plasma protein—antibodiesantibodies

Several plasma proteins—Several plasma proteins—complement, coagulation, complement, coagulation, kininkinin

Disease DeficienciesDisease Deficiencies

NutritionalNutritional

IatrogenicIatrogenic

TraumaTrauma

StressStress

Acquired Immunodeficiency (AIDS)Acquired Immunodeficiency (AIDS)

Immune - PrimaryImmune - Primary

Immunizations – ExposureImmunizations – Exposure

Activate B CellsActivate B Cells

Memory Cell Develops (B)Memory Cell Develops (B)

Secretion of AntibodiesSecretion of Antibodies

Pathogenic organism DEADPathogenic organism DEAD

Classes of Immunoglobulin'sClasses of Immunoglobulin's

IgM—produced first.IgM—produced first.

IgG—has “memory.”IgG—has “memory.”

IgA—involved in secretory immuneIgA—involved in secretory immune responses. responses.

IgE—involved in allergic reactions.IgE—involved in allergic reactions.

IgD—present in very lowIgD—present in very low concentrations. concentrations.

Immunoglobulin'sImmunoglobulin's

IgG (70 -75 %)IgG (70 -75 %)– Secondary immune Secondary immune

responseresponse

IgM (5-10 %)IgM (5-10 %)– ABO incompatibilitiesABO incompatibilities

IgA (15%) IgA (15%) – Defends body surface Defends body surface

against organismsagainst organisms

IgE IgE (less than 1%)(less than 1%)

– Immediate Immediate hypersensitivity hypersensitivity reactionsreactions

IgD IgD (less than 1%)(less than 1%)

Function unknownFunction unknown

HypersensitivityHypersensitivity

Altered immunologic reactivity to antigen Altered immunologic reactivity to antigen

Causes pathologic immune response after Causes pathologic immune response after reexposurereexposure

Abnormal responses include:Abnormal responses include:– AllergyAllergy– Autoimmunity – Host own cellsAutoimmunity – Host own cells– Isoimmunity – Beneficial foreign tissueIsoimmunity – Beneficial foreign tissue

Mechanisms of HypersensitivityMechanisms of Hypersensitivity

Immediate hypersensitivity reactionsImmediate hypersensitivity reactions– Itching, hivesItching, hives– AnaphylaxisAnaphylaxis

Delayed hypersensitivity reactionsDelayed hypersensitivity reactions– Take several hours to 1 to 2 days to appearTake several hours to 1 to 2 days to appear– At maximum several days after antigen At maximum several days after antigen

reexposure reexposure

IMMEDIATEIMMEDIATE

Antigen – Anti Body ReactionAntigen – Anti Body Reaction

– Mild- Itching HivesMild- Itching Hives

Severe – Life Threatening Severe – Life Threatening AnaphylaxisAnaphylaxis

DELAYEDDELAYED

Cell Immunity Hypersensitivity Cell Immunity Hypersensitivity

Hours – DaysHours – Days

Maximum Severity days laterMaximum Severity days later

Poison Ivy – Skin GraftsPoison Ivy – Skin Grafts

HomeostasisHomeostasis

QUAN QUAN QUAN QUAN

Stress & DiseaseStress & Disease

Think SympatheticThink SympatheticAdrenal GlandAdrenal Gland– Epi, Norepi, DopamineEpi, Norepi, Dopamine

Alpha & Beta EffectsAlpha & Beta Effects

Stress & DiseaseStress & Disease

Hypothalamus – pituitary glandHypothalamus – pituitary glandGrowthGrowth Blood pressureBlood pressure Some aspects of Some aspects of pregnancypregnancy and and childbirthchildbirth including including stimulation of uterine contractions during childbirth stimulation of uterine contractions during childbirth Breast milkBreast milk production production Sex organSex organ functions in both women and men functions in both women and men Thyroid glandThyroid gland function function The conversion of food into The conversion of food into energyenergy ( (metabolismmetabolism) ) WaterWater and and osmolarityosmolarity regulation in the body regulation in the body

Stress & DiseaseStress & Disease

CortisolCortisolSecreted by the adrenal glands and involved Secreted by the adrenal glands and involved

in the following functions and more: in the following functions and more:

Proper glucose metabolism Proper glucose metabolism – Regulation of blood pressure Regulation of blood pressure

– Insulin release for blood sugar maintenance Insulin release for blood sugar maintenance

Immune function Immune function

Inflammatory response Inflammatory response

Cortisol (Hydrocortisone)Cortisol (Hydrocortisone)

Circulates in the plasmaCirculates in the plasma

Mobilizes substances needed for cellular metabolismMobilizes substances needed for cellular metabolism

Stimulates gluconeogenesisStimulates gluconeogenesis– Decreases glucose utilizationDecreases glucose utilization

ImmunosuppressantImmunosuppressant

Decreases migration of macrophages Decreases migration of macrophages – Decreases phagocytosisDecreases phagocytosis

CatecholaminesCatecholamines

Stimulate:Stimulate:– Alpha-adrenergic receptorsAlpha-adrenergic receptors

Alpha-1 and alpha-2 Alpha-1 and alpha-2

– Beta-adrenergic receptorsBeta-adrenergic receptorsBeta-1 and beta-2Beta-1 and beta-2

Alpha ReceptorsAlpha Receptors

Alpha-1 receptorsAlpha-1 receptors– PostsynapticPostsynaptic– On the effector organsOn the effector organs– Stimulate contraction of smooth muscleStimulate contraction of smooth muscle

Alpha-2 receptorsAlpha-2 receptors– Presynaptic nerve endingsPresynaptic nerve endings– Stimulate alpha-2 receptors Stimulate alpha-2 receptors – Inhibit release of norepinephrine Inhibit release of norepinephrine

Beta ReceptorsBeta Receptors

Beta-1 receptorsBeta-1 receptors– Primarily in heartPrimarily in heart

Beta-2 receptorsBeta-2 receptors– Bronchiolar and Bronchiolar and

arterial smooth musclearterial smooth muscle

Beta receptorsBeta receptors– Stimulate the heartStimulate the heart– Dilate bronchiolesDilate bronchioles– Dilate blood vessels in Dilate blood vessels in

the skeletal muscle, the skeletal muscle, brain, and heartbrain, and heart

– Aid in glycogenolysisAid in glycogenolysis

STRESSSTRESS

NatureNature

IntensityIntensity

DurationDuration

PerceptionPerception

Coping SkillsCoping Skills

STRESSSTRESSSTRESSSTRESS

Stress: The confusion created when one's mind overrideStress: The confusion created when one's mind overrides the body's basic desire to choke the living daylights outs the body's basic desire to choke the living daylights out of some jerk who desperately deserves it of some jerk who desperately deserves it” ”

““Stress is when you wake up screaming and Stress is when you wake up screaming and you realize you haven't fallen asleep yet”you realize you haven't fallen asleep yet”

The Stress Response:The Stress Response:

Effects on the Sympathetic Nervous, Endocrine, Effects on the Sympathetic Nervous, Endocrine, and Immune Systems.and Immune Systems.

Effects on the Sympathetic Nervous, Endocrine, Effects on the Sympathetic Nervous, Endocrine, and Immune Systems.and Immune Systems.

QUESTIONSQUESTIONS QUESTIONSQUESTIONS