Transcript Chapter 8: Pathophysiology

Chapter 8
Pathophysiology
National EMS Education
Standard Competencies
Pathophysiology
Integrates comprehensive knowledge of
pathophysiology of major human systems
Introduction
• The human body is made up of cells,
tissues, and organs.
− Biology: study of living organisms
− Pathophysiology: study of organism in the
presence of disease
• To understand how disease may alter cellular
function, you must understand normal cellular
function.
Cells
• Basic self-sustaining unit
• Specialized through differentiation
• Three main components:
− Cell membrane
− Cytoplasm
− Nucleus
Cells
• Cell membrane:
− Made up fat and protein
− Surrounds the cell
− Protects the nucleus and organelles
Cells
• Organelles are structures within cytoplasm.
− Operate in cooperative and organized manner
− Contain:
• Ribosomes (contain ribonucleic acid [RNA])
• Endoplasmic reticulum
• Golgi complex
• Lysosomes and peroxisomes
• Mitochondria
• Nucleus
Cells
Tissues
• Groups of similar cells working together
• Types:
− Epithelial tissue: covers external surfaces and
lines hollow organs
− Connective tissue: binds other tissues to one
another
Tissues
• Types:
− Muscle tissue: characterized by its ability to
contract
• Skeletal muscle (striated voluntary)
• Cardiac muscle (striated involuntary)
• Smooth muscle (nonstriated involuntary)
Tissues
• Types:
− Nerve tissue: transmits nerve impulses
• Peripheral nerves extend from brain and spinal cord
• Neurons: main conducting cells of nerve tissue
• Dendrites: conduct impulses to cell body
• Axons: conduct impulse away from cell body
• Neurotransmitters: carry impulse from axon to
dendrite
Homeostasis
• Adaptive response to stressful environment
• Helps maintains equilibrium
• Apoptosis: genetically programmed cell
death
• Regulatory systems are counterbalanced by
counterregulatory systems.
Homeostasis
• Systems communicate at cellular level.
− Cells communicate through cell signaling.
− Feedback inhibition or negative feedback: when
action is completed, opposing system is alerted
to discontinue action.
Homeostasis
Homeostasis
• Receptors are specialized.
− Adrenergic receptors cause a sympathetic
response (vasoconstriction or vasodilatation).
− Baroreceptors and chemoreceptors are involved
in regulation of heart function.
Homeostasis
• Thermostat in a
house is similar to
body mechanisms
− Convection
− Conduction
− Radiation
− Evaporation
− Respiration
Homeostasis
• Body balances
what it takes in with
what it puts out.
• When cell signaling
is interrupted,
disease occurs.
− Excessive output
can upset
homeostasis.
Ligands
• Molecules that bind to receptors to form
more complex structures
− Endogenous ligands: produced by body
− Exogenous ligands: administered as a drug
Ligands
• Common ligands include:
− Hormones: substances formed in specialized
organs or groups of cells
• Endocrine: carried to target by the blood
• Exocrine: reach target via duct that opens into an
organ
• Paracrine: diffuse through intracellular spaces
• Autocrine: act on the cell from which it was secreted
Ligands
• Common ligands include:
− Neurotransmitters: proteins that affect signals of
the nervous system
− Electrolytes: dissolved mineral salts that
dissociate in solution, yielding ions
• Cations: positively charged
• Anions: negatively charged
Adaptations in
Cells and Tissues
• When exposed to adverse conditions, cells
undergo a process to protect themselves.
− Atrophy: decrease in cell size
− Hypertrophy: increase in cell size
− Hyperplasia: increase in cell number
− Dysplasia: alteration in cell size, shape, and
organization
− Metaplasia: cell type is replaced with another
Distribution of Body Fluids
• Intracellular fluid: 45% body weight
• Extracellular fluid: 15% body weight
− Interstitial fluid: surrounds tissues
− Intravascular fluid: within blood vessels
Distribution of Body Fluids
Fluid and Water Balance
• Average adult takes in 2,500 mL per day
− 60% lost through urination
− 28% lost through skin and lungs
− 6% lost in feces
− 6% lost in sweat
• Fluid moves through passive transport and
active transport.
Fluid and Water Balance
• Osmosis
− Movement from region of high water
concentration to lower concentration
• Hypertonic solution: high solute concentration
• Hypotonic solution: low solute concentration
• Isotonic solution: equal solute concentration
Fluid and Water Balance
Fluid and Water Balance
• Intracellular fluid volume controlled by:
− Proteins and organic compounds that cannot
escape through the cell membrane
− Sodium-potassium membrane pump
• Pump failure causes sodium to accumulate and
cells to swell.
Fluid and Water Balance
• Plasma
− Approximately 55% of blood
− Composed of 91% water and 9% proteins
− Starling hypothesis explains movement of water
between plasma and interstitial fluid
• Amount of fluid filtering through capillaries is equal
to amount of fluid returned by reabsorption.
Fluid and Water Balance
• Plasma (cont’d)
− Equilibrium between capillary and interstitial
space is controlled by four forces
• Capillary hydrostatic pressure
• Capillary colloidal osmotic pressure
• Tissue hydrostatic pressure
• Tissue colloidal osmotic pressure
Fluid and Water Balance
• Edema
− Occurs when excessive fluid builds up in the
interstitial space
− Causes include:
• Increased capillary pressure
• Decreased colloidal osmotic pressure
• Lymphatic vessel obstruction
Fluid and Water Balance
• Edema (cont’d)
− Assessment should include:
• Auscultation of lung sounds
• Evaluation for pedal/sacral edema and jugular
venous distention
• ECG and vital sounds
− Treatment may include diuretics, nitrates,
CPAP, high-flow oxygen, or advanced airway
placement
Fluid and Electrolyte Balance
• Maintained through a variety of factors
− Most important: thirst mechanism and release of
antidiuretic hormone (ADH)
− Hydration is monitored by:
• Osmoreceptors
• Volume-sensitive receptors
• Baroreceptors
Fluid and Electrolyte Balance
• Sodium
− Most common cation
− Regulates body’s acid-base balance
− Primary regulator: RAAS
• Excess sodium is excreted into urine.
Fluid and Electrolyte Balance
• Renin:
protein
released by
kidneys into
bloodstream
Fluid and Electrolyte Balance
• Chloride
− Important anion
− Assists in regulating acid-base balance
− Involved in osmotic pressure of extracellular
fluid
− Often follows sodium
Fluid and Electrolyte Balance
• Change in water causes cell change
− Tonicity: tension exerted on a cell during water
movement
− In isotonic solution: cells neither shrink or swell
− In hypertonic solution: cells shrinks
− In hypotonic solution: cells swell
Electrolyte Imbalance
• Sodium
− Hypertonic fluid deficit: caused by excess water
loss without proportionate loss of sodium
• Results in hypernatremia
− Hypotonic fluid deficit: caused by excess
sodium loss with less water loss
• Results in hyponatremia
Electrolyte Imbalance
• Potassium
− Normal level: 3.5 to 5 mEq/L
− Hypokalemia: decreased serum potassium level
− Hyperkalemia: elevated serum potassium level
• Calcium
− Normal level: 8.5 to 10.5 mg/dL
− Hypocalcemia: decreased serum calcium level
− Hypercalcemia: increased serum calcium level
Electrolyte Imbalance
• Phosphate
− Hypophosphatemia: decreased phosphate level
− Hyperphosphatemia: increased phosphate level
• Magnesium:
− Hypomagnesemia: decreased magnesium level
− Hypermagnesemia: increased magnesium level
Acid-Base Balance
• Acid: any molecule that can give up a
hydrogen ion
• Base (alkali): any molecule that can accept
a hydrogen ion
− Acidity or basicity (alkalinity) is determined by
the amount of free hydrogen in solution.
Acid-Base Balance
• pH: measurement of level of acidity or
alkalinity
− Normal pH is between 7.35 and 7.45.
Disturbances of
Acid-Base Balance
• Acids and bases neutralize each other and
must remain balanced.
− Acidosis: increase in extracellular H+ ions
− Alkalosis: decrease in extracellular H+ ions
• Disturbances are associated with potassium
balance
Buffer Systems
• Buffers: molecules that modulate pH
− Absence causes abrupt changes in pH
− Includes proteins, phosphate ions, and
bicarbonate
− Balances pH by absorbing or releasing
necessary amount of acid
Buffer Systems
Buffer Systems
• Primary buffer systems:
− Circulating bicarbonate: fastest means of
restoring balance
− Respiratory system: excessive acid is
eliminated through lungs
− Renal system: filters out hydrogen and retains
bicarbonate or reverse
Buffer Systems
• Circulating bicarbonate buffer component
− H2CO3  H+  HCO3–
• Respiratory buffer component
− H2CO3  CO2 + H2O
• Renal buffer component
− H2CO3  H+ + HCO3–
Types of Acid-Base Disorders
• Fluctuations in pH due to bicarbonate level:
metabolic acidosis or alkalosis
• Fluctuations in pH due to respiratory
disorders: respiratory acidosis or alkalosis
• A disorder not correctable by buffers
initiates compensatory mechanisms.
Types of Acid-Base Disorders
• Respiratory acidosis
− Related to hypoventilation
• Can quickly develop a potentially fatal acidosis
− Chronic COPD creates acidosis over time.
Types of Acid-Base Disorders
Types of Acid-Base Disorders
• Respiratory alkalosis
− Always caused by hyperventilation
• Life-threatening events may be responsible.
− Carbon dioxide levels drop.
− Renal system retains H+ ions.
• Results in Hypocalcemia
Types of Acid-Base Disorders
• Metabolic acidosis: any acidosis not related
to the respiratory system
− Causes include:
• Lactic acid
• Ketoacidosis
• Aspirin overdose
• Alcohol ingestion
• Gastrointestinal loses
Types of Acid-Base Disorders
• Metabolic alkalosis: occurs with excessive
acid loss
− Causes include:
• Upper gastrointestinal losses of acid
• Drinking large amounts of water during exercise
• Excessive intake of alkaline substances
− Compensatory mechanism: respiratory system
Types of Acid-Base Disorders
• Mixed acidosis: involves low pH, elevated
PCo2 level, and low HCO3 level.
− Both respiratory and metabolic acidosis are
present.
• Mixed alkalosis: involves elevated pH, low
PCo2, and elevated HCO3.
− Occurs when two unrelated medical issues
manifest at the same time
Cellular Injury
• Manifestations occur at microscopic and
functional levels.
− Microscopic abnormalities include:
• Cell swelling, rupture, breakdown of nuclear material
Cellular Injury
From An Introduction to Human Disease, 7th edition. Photo courtesy of Leonard V. Crowley, MD, Century College
Cellular Injury
• Damage and functional changes in cells
often impact the entire organism.
− Entire organ system may fail.
− Repair may occur with proper treatment.
• Irreversible injury will lead to cell death.
• Cell death is followed by necrosis.
Hypoxic Injury
• May result from:
− Decreased O2 in air
− Loss of hemoglobin function
− Decreased number of red blood cells
− Disease of respiratory or cardiovascular system
− Loss of cytochromes
Hypoxic Injury
• Cells that are hypoxic for more than a few
seconds produce mediators.
− Earliest and most dangerous: free radicals
− Chemical instability causes attacks on other
cells and membranes.
Chemical Injury
• Common poisons: cyanide and pesticides
• Lead: chronic ingestion leads to brain injury
and neurologic dysfunction
• Carbon monoxide: prevents adequate
oxygenation of tissues
Chemical Injury
• Ethanol: may result in CNS depression,
hypoventilation, and cardiovascular
collapse
• Pharmacologic agents: produce toxic
products when metabolized in the body
Infectious Injury
• Occurs as a result of an invasion of
bacteria, fungi, or viruses
• Virulence: measures disease-causing ability
− Pathogenicity: function of microorganism’s
ability to reproduce and cause disease
Infectious Injury
• Bacteria
− Possess a capsule that protects them from
phagocytes
− Categorized depending on Gram staining
• Gram-positive
• Gram-negative
Infectious Injury
Courtesy of Rocky Mountain Laboratory, NIAID, NIH
Infectious Injury
• Bacteria (cont’d)
− Produce exotoxins or endotoxins
− White blood cells release endogenous pyrogens
(cause a fever).
− Body’s most common reaction is inflammation
Infectious Injury
• Viruses
− Intracellular parasites
− Consists of nucleic acid core of RNA or DNA
− Capsid: protects from phagocytosis
− Replication occurs inside host cell
− Symbiotic relationship may be cause of
unapparent infection
Immunologic and
Inflammatory Injury
• Inflammation: protective response
− Can be triggered by physical, chemical, or
microbiologic agent
Immunologic and
Inflammatory Injury
Immunologic and
Inflammatory Injury
• Local effects: dilation of blood vessels and
increased vascular permeability
• Systemic effects: temperature elevation and
increased leukocytes
− Outcome depends on amount of tissue damage
• Cellular membranes may be injured in
process.
Injurious Genetic Factors
• Factors include:
− Chromosomal
disorders
− Premature
development of
atherosclerosis
− Obesity
• Abnormal gene may
develop:
− If gene mutates during
meiosis
− By heredity
− Due to other causes
later in life
Injurious Nutritional
Imbalances
• Injurious nutritional imbalances include:
− Obesity
− Malnutrition
− Vitamin or mineral excess or deficit
• Can lead to:
− Alterations in growth
− Mental and intellectual retardation
− Death
Injurious Physical Agents
or Conditions
• Physical agents include:
− Heat
− Cold
− Radiation
• Degree of cell injury is determined by:
− Strength of agent
− Length of exposure
Apoptosis
• Normal cell death
• During apoptosis:
− Cells exhibit characteristic nuclear changes and
die in clusters.
− Controlled degradation allows their remnants to
be taken up and reused.
Apoptosis
• Can be prematurely activated
by pathological
factors
− Forms of heart
failure
− Death of
hepatocytes
− Inhibition of normal
function
Abnormal Cell Death
• Necrosis: result of morphologic changes
following cell death
− Simple: gross and microscopic tissue and cells
are recognizable.
− Derived: caseation necrosis, dry gangrene, fat
necrosis, liquefaction necrosis
Factors That Cause Disease
• Genetic: present at birth, passed from one
generation to another
• Environmental: microorganisms, toxic
exposure, habits and lifestyle, physical
environment, etc.
• Anatomic: malrotation of the colon,
degenerative diseases, aortic stenosis
Factors That Cause Disease
• Uncontrollable:
− Genetics
− Race
• Controllable:
− Smoking
− Drinking alcohol
− Nutrition
− Physical activity
− Stress
Factors That Cause Disease
• Age-related risk
− Newborns: immune system not fully developed
− Teenagers: trauma, use of drugs and alcohol
− Older adults: cancer, heart disease, stroke
• Sex-associated factors
− Prevalence more in one sex than the other
− Presentation can differ from men to women
− Most sex-linked disorders are X linked
Analysis of Disease Risk
• Causal risk factors: causes disease
• No causal risk factors: associated with risk
• Consideration should include:
−
−
−
−
Incidence: number of new cases in population
Prevalence: number of cases in a period
Morbidity: presence of disease
Mortality: number of deaths
Analysis of Disease Risk
• Risk factors often interact.
Common Familial Diseases
• Genetic risk: passes through generations
• Familial tendency: cluster of diseases in
family groups despite lack of gene evidence
• Autosomal recessive: must inherit two
copies of a particular gene
• Autosomal dominant: needs to only inherit
one copy of a particular gene
Common Familial Diseases
• Immunologic disorders
− Hyper- or hypoactivity of immune system
− Most that exhibit familial tendencies involve an
overactive immune system
− Allergies: acquired following initial exposure
− Asthma: chronic inflammatory condition
Common Familial Diseases
Common Familial Diseases
• Cancer
− Large number of malignant growths
− Prognosis depends on extent of spread and
effectiveness of treatment
− Lung:
• Leading cause of death due to cancer
Common Familial Diseases
• Cancer (cont’d)
− Breast:
• Most common type of cancer in women
• Symptoms: small painless lump, change in nipple,
discharge, pain, and swollen lymph glands
− Colorectal:
• Third most common type of cancer
• Symptoms : minimal amount of blood in stools
Common Familial Diseases
• Endocrine disorders
− Diabetes mellitus: chronic disorder of
metabolism
• Ketoacidosis (type 1): insulin dependent
• No ketoacidosis (type 2): non-insulin dependent
Common Familial Diseases
• Hematologic disorder
− Hemolytic anemia: destruction of red blood cells
− Hemophilia: excessive bleeding
− Hemochromatosis: body absorbs more iron than
needed
Common Familial Diseases
Common Familial Diseases
• Cardiovascular disorders
− Long QT syndrome: cardiac conduction system
abnormality
− Consider syncope a life threat if:
• Exercise-induced syncope
• Syncope associated with chest pain
• History of syncope
• Syncope associated with startle
Common Familial Diseases
• Cardiovascular
disorders (cont’d)
− Cardiomyopathy:
diseases of the
myocardium
• Leads to heart
failure, acute
myocardial
infarction, or
death
Common Familial Diseases
• Cardiovascular disorders (cont’d)
− Mitral valve prolapse: mitral valve leaflets
balloon into the left atrium during systole
− Coronary heart disease: caused by impaired
circulation to the heart
− Hypertension: elevated blood pressure
Common Familial Diseases
• Renal disorders
− Gout: abnormal
accumulation of
uric acid
− Kidney stones:
masses of uric acid
or calcium salts
• Form in urinary
system
courtesy of Leonard Crowley
• Causes destructive
tissue changes
Common Familial Diseases
• Gastrointestinal disorders
− Malabsorption disorders: defect in bowel wall
prevents normal absorption of nutrients
• Lactose intolerance: defect in enzyme lactase
• Ulcerative colitis: chronic inflammatory disease of
the large intestine and rectum
• Crohn’s disease: chronic inflammatory disease
affecting the colon and small intestine
Common Familial Diseases
• Gastrointestinal disorders (cont’d)
− Peptic ulcer disease: circumscribed erosions in
the lining of the GI tract
− Gallstones: stone-like masses in the gallbladder
− Obesity: unhealthy accumulation of body fat
• Morbid obesity: BMI greater than 40 kg/m2
• Overweight: BMI of 25 to 29.9 kg/m2
Common Familial Diseases
• Neuromuscular disorders
− Huntington’s disease: characterized by
progressive chorea and mental deterioration
− Muscular dystrophy: group of hereditary
diseases of muscular system
• Duchene muscular dystrophy
− Multiple sclerosis: nerve fibers of the brain and
spinal cord lose myelin cover
• Neuromuscular
disorders (cont’d)
− Alzheimer’s
disease results in:
• Cortical atrophy
• Loss of neurons
courtesy of Leonard Crowley
Common Familial Diseases
courtesy of Leonard Crowley
• Ventricular
enlargement
Common Familial Diseases
• Psychiatric disorders
− Schizophrenia: group of mental disorders
• Distortions of reality, withdrawal, and disturbances
of thought, language, perception, and emotional
response
− Bipolar disorder: characterized by episodes of
mania and depression
Hypoperfusion
• Perfusion: delivery of oxygen and nutrients
and removal of wastes
• Hypoperfusion: level of perfusion drops
below normal
− Compensatory mechanisms set into motion
• Can be enough to stabilize the patient
• Can overwhelm compensatory mechanisms
Hypoperfusion
• Response to hypoperfusion:
− Release of catecholamines
− Activation of RAAS
− Release of antidiuretic hormone
− Fluid shifts from interstitial tissues to vascular
compartment
• Overall response: increase preload, stroke
volume, and heart rate
Hypoperfusion
• Persistence results in:
− Continued increase in myocardial demand
• Compensatory mechanisms no longer keep up
• Myocardial function worsens
• Tissue perfusion decreases
• Fluid leaks from vessels, causing systemic and
pulmonary edema
Types of Shock
• Shock: associated with inadequate oxygen
and nutrient delivery to cell
− Impairment of cell metabolism and inadequate
perfusion of vital organs
− Cells revert to anaerobic metabolism.
− Glucose impairment leads to elevated blood
glucose levels.
Types of Shock
• Shock can
occur due to
inadequacy of:
− Central
circulation
− Peripheral
circulation
Central Shock
• Cardiogenic
shock: heart
cannot circulate
enough blood
• Obstructive
shock: blood
flow becomes
blocked
Peripheral Shock
• Hypovolemic shock: blood is unable to
deliver adequate oxygen and nutrients
− Exogenous: external bleeding
− Endogenous: fluid loss contained within the
body
Peripheral Shock
• Distributive shock:
widespread dilation
of vessels
− Common types:
• Anaphylactic:
exposure to allergen
• Septic: result of
widespread infection
• Neurogenic: results
from spinal cord injury
Management of Shock
• Clinical determination requires:
− Evaluation of presence and strength or absence
of peripheral pulses
− Assessment of end-organ perfusion and
function
• Signs of shock include:
− Mottling, pallor, peripheral or central cyanosis,
and delayed capillary refill
Multiple Organ Dysfunction
Syndrome (MODS)
• Progressive condition that occurs in some
critically ill patients
− Characterized by concurrent failure of two or
more organs or systems
• Types:
− Primary MODS: direct result of an insult
− Secondary MODS: progressive organ
dysfunction
Multiple Organ Dysfunction
System (MODS)
• Occurs when injury or infection triggers
massive systemic immune, inflammatory,
and coagulation response
− Outcome is maldistribution of systemic and
organ blood flow
− During 14- to 21-day period, renal and liver
failure can develop
Body’s Self-Defense
Mechanisms
• Immune system: all structures and
processes associated with body’s defense
− Three lines of defense:
• Anatomic barriers
• Immune response
• Inflammatory response
Anatomic Barriers
• Decrease the chances of bodily invasion by
foreign substances
− Skin
− Hairs in upper respiratory tract and lining of
lower respiratory tract
− Acid in stomach
Immune Response
• Body’s defense reaction to any substance
that is recognized a foreign
• Involves only one type of white blood cells
(lymphocytes)
Immune Response
• Lymphatic system: network of capillaries,
vessels, ducts and nodes, and organs
Immune Response
Immune Response
• Lymphoid tissues:
− Primary tissues: bone marrow and thymus
gland
− Secondary tissues: encapsulated (lymph nodes
and spleen) and unencapsulated
• Lymph: thin watery fluid that bathes tissues
− Circulates through lymph vessels and filtered in
lymph nodes
Immune Response
• Mucosal-associated lymphoid tissue:
clusters of lymphoid tissue
− Example: tonsils
• Gut-associated lymphoid tissue:
unencapsulated lymphoid tissue in the GI
tract
Immune Response
• Leukocytes: primary cells of the immune
systems
Immune Response
• Mast cells: resemble basophils
Immune Response
• Characteristics:
− Natural immunity: nonspecific cellular and
humoral response (first line of defense)
− Acquired immunity: highly specific method in
which cells respond to a stimulant
• Passively acquired: preformed antibodies (mother to
infant)
Immune Response
• Primary response takes place during first
exposure to an antigen.
• Secondary response occurs with repeat
exposure to an antigen.
Immune Response
• Antibody: binds
antigen so that
complex can
attach itself to
immune cells
that destroy the
complex
Immune System
• Immunogenic: antigen capable of
generating an immune response against
itself
− Happen: substance that normally does not
stimulate immune response but can be
combined with an antigen and later initiate an
antibody response
Humoral Immune Response
Humoral Immune Response
• B cell lymphocytes produce antibodies.
− Clonal selection theory: each B cell makes
antibodies that have only one type of antigen
binding region
− For B cells to produce antibodies, they must be
activated.
Humoral Immune Response
Humoral Immune Response
• Activation often occurs via helper T cells.
− Macrophage engulfs antigen, and discarded
particles interact with B cells and helper T cells.
− Antigen binds to B cell and helper T cell
− Helper T cell stimulates B cell to produce clone
Immunoglobins
• Immunoglobins:
antibodies
secreted by B cells
− Consist of
crystallizable
fragment portion
and two antigenbinding fragment
regions
Immunoglobins
• Three main antigens on antibodies
− Isotypic: occurs in all subclasses of
immunoglobin class
− Allotypic: found on some members of a
subclass immunoglobin class
− Idiotypic: unique structure created on an
immunoglobulin molecule
Immunoglobins
• Antibodies make
antigens more
visible by:
− Opsonization:
antibody coats
antigen
− Cause antigens to
clump
− Bind to and
inactivate some
toxins
Cell-Mediated Immune
Response
• Characterized by formation of lymphocytes
• Main defense against virus, fungi, parasites,
and some bacteria
Cell-Mediated Immune
Response
• Mechanism by which body rejects
transplanted organs and eliminates
abnormal cells
• T cells lymphocytes recognize antigens by:
− Secreting cytokines
− Becoming cytotoxic and killing abnormal cells
Cell-Mediated Response
• Five subcategories of T cells:
− Killer T cells: destroy antigen
− Helper T cells: activate immune cells
− Suppressor T cells: suppress activity of other
lymphocytes
− Memory T cells: remember reaction
− Lymphokine-producing cells: damage or destroy
infected cells
Cellular Interaction
in Immune Response
• Basic pattern:
− Bacteria enters body.
• Not encapsulated: macrophages ingest them
• Encapsulated: antibodies coat capsule before
ingestion
− Cell wall activates complement system.
− Membrane attack complex is formed.
− Memory B cells or B cells will be activated.
Inflammatory Response
• Response of the body to irritation or injury
− Characterized by pain, swelling, redness, and
heat
• Most common causes: injury and illness
Inflammatory Response
• Acute inflammation
− Involves both vascular and cellular components
− Active hyperemia causes blood vessels to
expand.
• Fluid leaks into interstitial spaces.
− When pressure is released, vessel contacts and
outflow slows.
• Leads to stasis of blood in capillaries
Inflammatory Response
• Acute inflammation (cont’d)
− Variety of cells participate:
• White blood cells
• Platelets
• Mast cells
• Plasma cells
− Chemical mediators account for vascular and
cellular events.
Inflammatory Response
• Mast cells: degranulate and release
substances
− Major stimuli for degranulation:
• Physical injury
• Chemical agents
• Immunological substances
− Release vasoactive amines.
− Synthesize leukotrienes and prostaglandins.
Plasma Protein Systems
• Mediators that modulate the inflammatory
response
• Complement system: proteins attract white
blood cells to sites of inflammation
− Cells are activated, then destroyed
− Classic or alternate pathway
− Components: C3b, anaphylatoxins, membrane
attack complex
Plasma Protein Systems
• Coagulation system: forms blood clots and
repairs vascular tree
− Inflammation triggers fibrin formation.
• Fibrin: protein that bonds to form the fibrous
component of a blood clot
− Fibrinolysis cascade: dissolves fibrin and
creates fibrin split products
Plasma Protein Systems
• Kinin system: leads to the formation of
bradykinin from kallikrein
− Kallikrein: enzyme found in blood plasma, urine,
and tissues (normally inactive)
− Bradykinin: increases vascular permeability,
dilates blood vessels, contracts smooth muscle,
and causes pain when injected
Cellular Components
of Inflammation
• Goal: arrive at the sites within tissues where
they are needed
• Two major stages:
− Intravascular stage: leukocytes move to sides of
blood vessels and attach to endothelial cells
− Extravascular stage: leukocytes travel to the
site of inflammation and kill organisms
Cellular Components
of Inflammation
• Cellular event sequence:
− Margination: increase in blood viscosity
− Activation: mediators trigger the appearance of
selectins and integrins
− Adhesion: PMNs attach to endothelial cells
− Transmigration: PMNs permeate vessel walls
− Chemotaxis: PMNs move to site of inflammation
Cellular Components
of Inflammation
Cellular Products
of Inflammation
• Cytokines: products of cells that affect other
cells
− Interleukins: attract white blood cells to sites of
injury
− Interferon: protein produced by cells invaded by
viruses
Cellular Products
of Inflammation
• Lymphokines: stimulates leukocytes
− Macrophage-activating factor stimulates
macrophage to engulf and destroy
− Migration inhibitory factor keeps white blood
cells at site of infection or injury
Injury Resolution and Repair
• Normal wound healing involves four steps:
− Repair of damaged tissue
− Removal of inflammatory debris
− Restoration of tissues
− Regeneration of cells
Injury Resolution and Repair
• Healing depends on the type of cells:
− Labile cells: divide continuously
− Stable cells: replaced by regeneration
− Permanent cells: cannot be replaced
• Wounds can be healed by:
− Primary intention: occurs in clean wounds
− Secondary intention: occurs in gaping wounds
Injury Resolution and Repair
• Factors that lead to dysfunctional healing:
− Local: infection, inadequate blood supply,
foreign bodies
− Systemic: poor nutritional intake and
hematologic abnormalities
• Diabetes and AIDS
• Corticosteroids
• Wound separation
Chronic Inflammatory
Response
• Causes include:
− Unsuccessful acute inflammatory response
− Persistent infection
− Presence of an antigen
• Similar to acute inflammation process
− Also include growth of new blood vessels
Variances in Immunity
and Inflammation
• Hypersensitivity: response to any substance
to which a patient has increased sensitivity
− Allergy: reaction to an agent (allergen)
− Autoimmunity: antibodies or T cells work
against the tissues
− Isoimmunity: T cells or antibodies are directed
against antigens on other cells
Variances in Immunity
and Inflammation
• Type I: immediate
hypersensitivity reaction
− Acute reaction to a
stimulus
− Symptoms depend on
mediator release
− Treatment includes:
• Administration of
epinephrine
• Subcutaneous injection
Variances in Immunity
and Inflammation
• Type II: cytotoxic hypersensitivity
− Involves combination of IgG or IgM antibodies
with antigens
− Cells are destroyed by complement fixation or
by other antibodies.
− Example: blood transfusion
Variances in Immunity
and Inflammation
• Type III: tissue injury caused by immune
complexes
− Involves IgG antibodies that form immune
complexes with antigen
− Reactions may be:
• Systemic (serum sickness)
• Localized (Arthus reaction)
Variances in Immunity
and Inflammation
• Type IV: delayed (cell-mediated)
hypersensitivity
− Mediated by soluble molecules released by
specifically activated T cells
− Subtypes:
• Delayed hypersensitivity
• Cell-mediated cytotoxicity
Variances in Immunity
and Inflammation
• Targets of hypersensitivity reactions:
− Allergic reaction: antigen or allergen
− Autoimmune: person’s own tissue
• Graves’ disease: caused by thyroid-stimulating or
thyroid-growth immunoglobulins
• Type I diabetes: body produces autoantibodies
• Rheumatoid arthritis: chronic systemic disease
Variances in Immunity
and Inflammation
• Targets of hypersensitivity reactions:
− Autoimmune: person’s own tissue
• Myasthenia gravis: attack on nerve muscles
• Neutropenia: decrease in circulating neutrophils
• Immune thrombocytopenia purpura (ITP): patient
forms antibodies to blood platelets
• Systemic lupus erythematosus: immune system is
directed against tissues
Variances in Immunity
and Inflammation
• Targets of hypersensitivity reactions:
− Blood group antigens
• Rh factor: antigen present in erythrocytes
• Blood type is determined by antigens.
−
−
−
−
Type A
Type B
Type AB
Type O
Immune Deficiencies
• Immunodeficiency: abnormal condition in
which part of immune system is inadequate
• Congenital immunodeficiencies:
− Defects include lymphoid stem cells and T and
B cells
− Two types both inherited:
• X-linked agammaglobulinemia
• Isolated deficiency of IgA
Immune Deficiencies
• Acquired
immunodeficiencies
− Contributors:
• Nutritional deficiency
• Stress of trauma
•
•
•
•
Hypoperfusion or shock
Mediator production
Damage to vital organs
Decreased nutrition
occurring during trauma
Immune Deficiencies
• Acquired immunodeficiencies (cont’d)
− Iatrogenic (treatment-induced)
immunodeficiency
− AIDS: caused by RNA retrovirus HIV
Immune Deficiencies
• Treatment of immunodeficiencies:
− Replacement therapy for some types
• Intravenous gamma globulin
• Bone marrow transplant
• Transfusions
Stress and Disease
• Stress
− Range of strong
external stimuli that
can cause a
physiologic
response
• Physiologic stress
− Change that
makes it necessary
for cells to adapt
Stress and Disease
• Physiologic stress (cont’d)
− Three concepts:
• The stressor
• Its effect
• Body’s response
• Usually the response is beneficial.
− Unchecked stress can result in deleterious
outcomes.
General Adaptation Syndrome
• Stage 1: Alarm
− Body reacts by releasing catecholamines
− Catecholamines activate the sympathetic
nervous system.
− Effects include:
• Increased respiratory rate
• Decreased blood flow to skin
• Smooth muscle constriction
• Effects on the liver
General Adaptation Syndrome
• Stage 2: Resistance
− Adrenal gland releases two types of hormones
that increase blood glucose level and maintain
blood pressure
• Glucocorticoids and mineralocorticoids
General Adaptation Syndrome
• Stage 2: Resistance (cont’d)
− Hypothalamus stimulates the
release of ACTH
− Other hormones released
include:
• Endorphins
• Growth hormone
General Adaptation Syndrome
• Stage 3: Exhaustion
− Adrenal glands depleted
− Diminishing levels of glucose
− Results in:
• Decreased stress tolerance
• Progressive mental and physical exhaustion
• Illness
• Collapse
Effects of Chronic Stress
• Hypothalamic-pituitary-adrenal axis: major
part of the neuroendocrine system
− Controls the reaction to stress
− Triggers a set of interactions among gland,
hormones, and parts of the midbrain
− Continued stress exhausts the normal
mechanisms.
Effects of Chronic Stress
• Stress and depression have a negative
effect on the immune system.
− Body loses ability to fight disease
− Body releases fat and cholesterol into the blood
Effects of Chronic Stress
• Coping mechanisms
− Healthy person: manages stress with very little
impact on immune system
− Ineffective coping mechanisms lead to
deleterious effects on the immune system
• Treatment includes psychotherapy,
medication, or positive influences.
Summary
• Pathophysiology is the study of the
functioning of an organism in the presence
of disease.
• All cells except red blood cells and platelets
have three main components: a nucleus,
cytoplasm, and a cell membrane.
• There are four major tissue types: epithelial
tissue, connective tissue, muscle tissue,
and nervous tissue.
Summary
• When cells are exposed to adverse
conditions, they undergo a process of
temporary or permanent adaptation.
• The cellular environment refers to the
distribution of cells, molecules, and fluids
throughout the body.
• Electrolytes in body fluids include sodium,
chloride, potassium, calcium, phosphorus,
and magnesium.
Summary
• pH is a measurement of the hydrogen ion
concentration of a solution.
• Cellular injury is caused by factors such as
hypoxia, chemical exposure, infectious
agents, inappropriate immunologic
responses, inflammatory responses, genetic
factors, nutritional imbalances, physical
agents.
Summary
• Inflammatory response is characterized by
both local and systemic effects. The
outcome of an inflammation depends on
how much tissue damage has resulted from
the inflammation.
• Age- and sex-associated factors interact
with a combination of genetic and
environmental factors, lifestyle, and
anatomic or hormonal differences to cause
disease.
Summary
• Analyzing disease risk involves
consideration of disease rates (incidence,
prevalence, morbidity, and mortality) and
controllable and uncontrollable disease risk
factors (causal and noncausal).
• A true genetic risk is passed through
generations on a gene. In contrast, a
familial tendency may cluster in family
groups despite lack of evidence for heritable
gene-associated abnormalities.
Summary
• In autosomal dominant inheritance, a
person needs to inherit only one copy of a
particular form of a gene to show the trait. In
autosomal recessive inheritance, the person
must inherit two copies of a particular form
of a gene to show the trait.
• Immunologic diseases occur because of
hyperactivity or hypoactivity of the immune
system. Allergies are acquired following
initial exposure to an allergen.
Summary
• Perfusion is the delivery of oxygen and
nutrients to cells, organs, and tissues
through the circulatory system.
Hypoperfusion occurs when the level of
tissue perfusion falls below normal.
• Shock is an abnormal state associated with
inadequate oxygen and nutrient delivery to
the metabolic apparatus of the cell, resulting
in an impairment of cellular metabolism.
Summary
• Central shock consists of cardiogenic shock
and obstructive shock.
• Peripheral shock includes hypovolemic
shock and distributive shock.
• Multiple organ dysfunction syndrome
(MODS) occurs in acutely ill patients and is
characterized by the dysfunction of two or
more organs that were not affected by the
physiologic insult for which the patient was
initially being treated.
Summary
• The immune system includes all of the
structures and processes that mount a
defense against foreign substances and
disease-causing agents.
• The body has three lines of defense:
anatomic barriers, the inflammatory
response, and the immune response.
Summary
• The two anatomic components of the
immune system are the lymphoid tissues
and the cells responsible for an immune
response.
• The primary cells of the immune system are
the white blood cells, or leukocytes.
• There are two general types of immune
response: native and acquired.
• Immunity may be humoral or cell-mediated.
Summary
• Important white blood cells in the immune
system include neutrophils, eosinophils,
basophils, monocytes, and lymphocytes.
Other important cells of the immune system
include macrophages, mast cells, plasma
cells, B cells, and T cells.
• The antibodies secreted by B cells are
called immunoglobulins. Antibodies make
antigens more visible to the immune
system.
Summary
• The inflammatory response is the reaction
of the body’s tissues to cellular injury.
• The two most common causes of
inflammation are infection and injury.
• The plasma protein systems that modulate
the inflammatory process include the
complement system, the coagulation
(clotting) system, and the kinin system.
Summary
• Cytokines are products of cells that affect
the functioning of other cells; they include
interleukins, lymphokines, and interferon.
• Chronic inflammatory responses are usually
caused by an unsuccessful acute
inflammatory response after the invasion of
a foreign body, a persistent infection, or an
antigen.
Summary
• Normal wound healing involves four steps:
repair of damaged tissue, removal of
inflammatory debris, restoration of tissues
to a normal state, and regeneration of cells.
• Wounds may heal by primary or secondary
intention. Healing by primary intention
occurs in clean wounds with opposed
margins. Wounds that heal by secondary
intention have a prolonged inflammatory
phase.
Summary
• Hypersensitivity is an increased response of
the body to any substance to which the
person is abnormally sensitive.
• Hypersensitivity reactions may be classified
as autoimmune, idiopathic, or blood
incompatibility reactions.
• Immunodeficiency may be congenital or
acquired.
Summary
• Stress does not cause death directly, but it
can permit diseases to flourish, ultimately
leading to death.
• The general adaptation syndrome describes
the body’s short-term and long-term
reactions to stress.
Summary
• Stress causes the sympathetic nervous
system to be stimulated. This occurs
through release of catecholamines that
activate the sympathetic nervous system.
• Stress also causes secretion of cortisol,
which has many useful effects. However,
continuous secretion of cortisol has
deleterious effects.
Credits
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Learning. Courtesy of MIEMSS; Purple—Jones & Bartlett
Learning. Courtesy of MIEMSS; Blue—Courtesy of
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• Unless otherwise indicated, all photographs and
illustrations are under copyright of Jones & Bartlett
Learning, courtesy of Maryland Institute for Emergency
Medical Services Systems, or have been provided by the
American Academy of Orthopaedic Surgeons.