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Pathophysiology Exam 1
n/a
103
Nursing
08/22/2012

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Term
atrophy
Definition
decrease in cell size
Term
hypertrophy
Definition
increase in cell size; cells of heart and kidneys particularly responsive to enlargement; increase in cellular size is associated with an increased accumulation of protein in the cellular components (plasma membrane, ER, myofilaments, mitochondria); can be physiologic or pathologic & is caused by specific hormone stimulation or increased functional demand
Term
hyperplasia
Definition
increase in cell number
Term
metaplasia
Definition
reversible replacement of one mature cell type by another less mature cell type
Term
dysplasia
Definition
deranged cellular growth (not considered a true cellular adaption but rather an atypical hyperplasia)
Term
Mechanisms of Hypertrophy
Definition
  • hormonal stimulation (uterus in pregnancy)
  • ↑ functional demand (exercise, myocardial failure, ↑ cardiac workload)
  • ↑ cell size from cellular protein accumulation, not fluid (heart, kidneys)
  • physiologic hypertrophy reversible
  • triggers: mechanical (stretch) and trophic (growth factor and vasoactive agents) signals
Term

Mechanisms of Hyperplasia

 

Definition
  • loss of epithelial cells → ↑ rate of cell division
  • physiologic: compensatory (liver regeneration) and hormonal (↑ estrogen & mam glands during preg) [note: nerves, skeletal muscle, myocardial cells, & optical lenses DO NOT regenerate]
  • pathologic: endometrial hyperplasia or neoplasms
  • may occur with hypertrophy (except in such non-dividing cells as myocardial fibers)
Term

Mechanisms of Metaplasia

 

Definition
  • reprogramming of stem cells (epithelia) or undifferentiated mesenchymal cells (connective tissue)
  • different cell maturation pathway signaled by cytokines and growth factors
  • bronchial: smoking (reversible v. neoplasm)
         -ciliated, columnar epithelial cells replaced with    stratified squamous epithelial cells
Term
Common Biochemical Derangements of Cell Injury & Death
Definition
  • ↓ ATP: cellular swelling, ↓ protein synthesis, ↓ membrane transport, lipogenesis
  • ROS: destroy cell membranes and structure
    - inactivate enzymes, damage cell membrane,
       injure nucleic acids (DNA)
  • ↑ Ca in cell: intracellular damage from enzyme activation
  • membrane permeability defects: ↓ protein, co-enzymes, RNA, and ATP substrates

 

Term
Definition
[image]
Term
Cellular Injury Mechanisms: Chemical
Definition
  • toxin- cell membrane interaction
    -direct toxicity
    -free radicals, lipid peroxidation
    -cellular responses
          -lipid accumulation
          -membrane defects → cellular swelling
          - ↓ ATP, Ca++ influx into mitochondira (↓oxidative metabolism)
          - DNA degradation
          - Lysosomal membrane injury→enzyme leak into cytoplasm→digestion of all cell organelles→DNA synthesis halted
    -air pollutants, insecticides, social drugs, etc.
  • Lead toxicity
    -heavy metal, lungs and GI absorption
    -↑ intracellular Ca++→ neurotransmitter interference (alters fetal & pediatric neurodevelopment, learning disorders, hyperactivity, attention deficit, convulsions)
    -↓ enzymes for Hgb synthesis & RBC lysis (hemolysis)→anemia
    -renal deposits→tubular dysfunction (glycosuria, proteinuria, hyperphosphaturia)
    -lead based paint/toys, glazed pottery, print shop, plumbing, engine repair
  • CO poisoning:
    -odorless, colorless gas
    -incomplete combustion of fuel
    -interferes with cellular respiration
    -affinity for Hgb 300X > than O2
    -binds to Hgb (carboxyhemoglobin)-prevents O2 binding→hypoxia (HA, giddiness, tinnitus, N/V)
    -↑fetal risk
Term
Cellular Injury Mech: Hypoxia
Definition
  • ischemia/anoxia (arteriosclerosis, thrombosis)
    -↓ ventilation, perfusion, diffusion, & O2 binding to Hgb
    -resp diseases, MI, hemorrhagic shock, poisons, toxins
    -cellular responses
           -↓ ATP→anaerobic metabolism
           - Na+ K+ pump failure→↑ Na+ & Ca++ & ↓ K+ in cell
           - cellular swelling (Na+ influx)
    -Reperfusion injury
           -enzyme conversion
           - ↑ATP consumption during ischemia → catabolites → ↑ ROS
               reperfusion → cell membrane damage, ATP loss, apoptosis

           -Rx: antioxidants, anti-inflammatories
Term
What happens during ischemia?
Definition
  1. progessive loss of O2
  2. shift from aerobic to anaerobic
  3. buildup of lactic acid
  4. rapid ↓ in mitochondrial phosphorylation, due to lack of O2
  5. LOSS OF ATP
  6. Na+, K+ pump and Na+, Ca++ exchange failure
  7. influx of Na+ & Ca++, release of K+
  8. cellular swelling as H2O enters cell
  9. dilation of ER, detachment of Ribosomes, loss of protein synthesis
    **at this point, process is reversible**
  10. vacuolation
  11. activation of multiple enzymes & lysosomes
  12. DNA degradation
  13. Cell death
Term
Cellular Injury Mech: ROS
Definition
  • Free radicals
    -electrically unstable molecule(s)
    -disrupt chemical bonds of cell membranes (b/c free radical will bond with proteins, lipids, carbs)
    -destroy cell membrane & structure
  • ROS
    -low levels beneficial?
    -high levels → apoptosis, necrosis
    -lipid peroxidation (destruction of unsaturated fatty acids, also lipid-radical interactions yield peroxides), alterations of proteins causing fragmentation of polypeptide chains) & DNA alterations
    -inactivation of free radicals (antioxidants, enzymes)
    -all cells capable of making ROS, but effects of inflammatory & CV disease (e.g. HTN, ischemic heart disease) widespread
Term
Cellular Injury Mech: Hematomas
Definition
  • collection of blood in soft tissue v. enclosed space
  • subdural: blook bt brain & surface dura
    -venous blood, slow
    -fall, blow, sudden acceleration, deceleration
  • epidural: blood bt dura & skull
    -arterial blood, fast
    -skull fracture
Term
Manifestations of Cellular Injury
Definition
  • Cellular accumulations (infiltrations)
    -water, lipids, carbs, glycogen, proteins, pigments, Ca++, urate
    -crowd organells, release metabolites
  • excess endogenous production, ineffective catabolism, or exogenous exposure
  • migration of phagocytes→tissue swelling
  • reversible (liver cirrhosis) or irreversible (exogenous poisoning)
Term
Manifestations of Cellular Injury: Clinical
Definition
  • fever- endogenous pyrogens, acute inflammatory response
  • ↑ HR- ↑ metabolism
  • ↑WBC- infection
  • pain- bradykinins, pressure
  • ↑ enzymes (LDH, CK, AST, ALT, ALP, amylase)
Term
Oncosis
Definition
vacuolar or hydropic degeneration; happens during cellular swelling (in hypoxia, loss of ATP and metabolic function causes Na+ to build up in cell resulting in ↑ osmotic pressure resulting in increase in water inside the cell. vacuoles are created to isolate the water from the cytoplasm; basically oncosis is a degeneration of the cell by water)
Term
Cell Death: Sequence of Events
Definition
  • ↓ ATP production
  • Na+ - K+ pump (active transport) failure
  • cellular swelling (NaCl influx into cells)
  • ribosome detachment from ER
  • ↓ protein synthesis
  • intracellular Ca++ → mitochondrial swelling
  • cytoplasmic vacuolation
  • lysozome leakage of digestive enzymes
  • autodigestion of intracellular structures (nucleus, nucleolus, halting DNA/RNA synthesis)
  • plasma membrane lysis
Term
Cellular Death: Necrosis
Definition
  • sum of cellular changes after local cell death & process of cellular autodigestion
  • widespread
  • cell swelling
  • rupture of cellular organisms
  • inflammatory response
  • causes: prolonged hypoxia, infection, cell membrane damge
Term
Coagulative Necrosis
Definition
  • definition: sum of cellular changes following cell death occuring primarily in the kidneys, heart & adrenal glands; commonly results from hypoxia
  • etiology: protein denaturation of plasma proteins, which causes albumin to change from a gelatinous state to a firm, opaque state
  • pathogenesis:
    -severe ischemia
    -chemical injury (HgCl)
    -abnormalities in intracellular levels of Ca++
Term
Gangrene Necrosis
Definition
  • definition: refers to death of tissue
  • etiology: hypoxic injury, commonly associated with arteriosclerosis, especially in the lower leg
  • pathogenesis
    -arterial blockage
    -subsequent bacterial invasion
    -Dry gangrene- result of coagulative necrosis
    -wet gangrene- develops when neutrophils invade the site; causes liquefactive necrosis
    -gas gangrene- caused by infection by Clostridium
Term
Liquefactive Necrosis
Definition
  • definition: necroses which commonly results from injury to neuron and glial cells in the brain
  • etiology: hydrolytic enzymes (hydrolases) from dead brain cells digest surrounding brain cells; liquified tissue is then walled off from healthy tissue, forming cysts
  • pathogenesis:
    -ischemic injury to neuron/glial cells
    -bacterial infection, causing release of neutrophil hydrolases; pus accumulation
Term
Caseous necrosis
Definition
  • commonly results from TB infection; is a combo of coagulative & liquefactive necrosis
  • the dead cells disintegrate, but the debris isn't digested completely by hydrolases
  • tissues resemble clumped cheese
  • a granulomatous inflammatory wall encloses areas of causeous necrosis
Term
Cellular Death: Apoptosis
Definition
  • programmed cellular death (scattered, single cells)
  • enzyme synthesis, protease-induced shrinkage, cell fragmentation, phagocytosis
  • apoptosis (physiologic or pathologic)
    -single cell, nuclear/cytoplasm shrinkage, quick & clean; no swelling or inflammation
  • vs. necrosis (pathologic)
    -tissue cells swell & lyse, slow & messy, inflammation of neighboring cells
Term
[image]
Definition
Term
ICF & ECF Water Movement
Definition
  • osmotic forces (passive transport)
    -primary control/regulation
  • aquaporins (H2O channel proteins, provide permeability to H2O)
  • starling hypothesis
    -NET Filtration
             -movement of H2O from capillary to interstitial space
             *F favoring filtration-F opposing filtration
             *(cap hydrostatic + interstitial oncotic) - (plasma oncotic + interstitial hydrostatic)
Term
Active transport
Definition
  • mediated, needs energy
  • Na+, K+, Ca++, amino acids moved by active transport w/carrier against concentration gradient
  • Na+ K+ pump carrier protein
  • Na+ K+ ATPase: enzyme splits ATP for energy
    -proteins/organic substances cannot cross cell membrane (↑ ICF osmotic pressure, H2O diffuses into cell)
  • 3 Na+ ions from ICF→ECF; 2 K+ ions from ECF→ICF (↓ ICF osmotic pressure & H2O diffusion)
  • electrical gradient (membrance potential)
    -nerve & muscle function, APs
Term
Net Filtration
Definition
  • forces favoring filtration (arterial end)
    -cap hydrostatic P (BP)
    -interstitial oncotic P (H2O pulling)
  • forces favoring reabsorption (venous end)
    -plasma oncotic P (H2O pulling)
    -interstitial hydrostatic P
  • capillary membrane damage
    -movement of proteins to interstitial→edema
Term
edema
Definition
  • accumulation of fluid in interstitial space
  • local or systemic: not available for perfusion/metabolism (3rd space)
    -lymphodema, pitting edema, cerebral edema, pulmonary edema, ascites
    -weight gain, swelling, puffiness, impaired wound healing
  • causes:
    -↑ cap hydrostatic P (venous constriction, Na+ & H2O retention)
    -↓ plasma albumin (liver disease, protein malnutrition)
    -↑ cap permeability (inflammatory & immune cell injury causes)
    -lymph obstruction (infection, tumor, surgical removal)→ lymphedema
  • Rx: elevation, compression, ↓ Na + intake, diuretics, underlying cause
Term
[image]
Definition
Term
Na+ Regulation
Definition
  • ↑ glomerular filtration rate (GFR)
  • renin-angiotensin-aldosterone (RAA)
    -aldosterone secreted when
           - ↓ Na+
           - ↑ K+
           - ↓ blood volume
  • natriuretic peptides (RAA antagosnists: ↓BP, ↑Na+ & H2O excretion)
    -atrial natriuretic peptide (ANP - atria)
    -brain natriuretic peptide (BNP - ventricles)
    -urodilantin (kidneys)
Term
Na+, Cl-, H2O balance - alterations
Definition
  • infants, obese, & elderly - ↑ risk for imbalance
  • isotonic alterations
    -total body water change, proportional electrolyte & H2O change, no cellular shrinking or edema
    -hypovolemia→ ↓ atrial P → ↑ ADH secretion
    -isotonic volume depletion (hemorrhage, wound drainage, diaphoresis, intestinal loss) → ↓ weight, dry skin & mucous membranes), ↑ HR, ↓ U.O.
    -isotonic volume excess (IV, ↑ aldosterone secretion with renal Na+ & H2O retention, corticosteroids, renal failure)
Term
Hypertonic alterations: H2O defecit
Definition
  • intracellular dehydration →hypovolemia
    -dehydration
    -pure H2O deficits
    -renal free H2O clearance
    -hyperglycemia
  • manifestations
    -tachycardia, ↓ BP, thirst, fever
    -↑ hematocrit & serum Na+
  • Rx: slow D5W
Term
Hypertonic Alterations: Hypernatremia
Definition
  • serum sodium >147 mEq/L
  • related to sodium gain or water loss
  • water movement from the ICF to the ECF
    -intracellular dehydration (cells shrink)
    -hypervolemia
  • manifestations:
    -convulsions, pulmonary edema, fever, tachycardia, confusion, coma
  • Rx with D5W
Term
Potassium
Definition
  • major intracellular cation
  • concentration maintained by Na+ K+ pump
  • regulates intracellular electrical neutrality in relation to Na+ & H+
  • essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction
Term
Potassium Levels
Definition
  • changes in pH & K+ balance
    -H+ accumulates in ICF with acidosis
    -K+ shifts out to maintain cation balance across membrane
  • aldosterone, insulin, and catecholamines influence serum potassium levels
Term
Hyperkalemia
Definition
  • Potassium level > 5.5 mEq/L
  • Hyperkalemia is rare due to efficient renal excretion
  • caused by shift of K+ (metabolic acidosis), ↓ renal excretion (renal failure), insulin deficiency, cell trauma (e.g. crush injuries), acidosis
  • Rx: insulin (K+ & glucose from ECF→ICF)
  • Mild
    -hyperpolarized membrane→neuromuscular irritability
           -tingling of lups and fingers, restlessness, intestinal cramping, and diarrhea
  • Severe
    -cell unable to repolarize→muscle weakness, loss or muscle tone, flaccid paralysis, arrhythmia, peaked T wave, ↓ ST segment, wide QRS
  • Rx: correct acid-base, Ca++ gluconate, glucose, NaHCO3, dialysis, insulin (K+ & glucose from ECF→ICF)
Term
Hypocalcemia
Definition
  • ↓s block of Na+ into cell
  • ↑ neuromuscular excitability (partial depolarization)
  • muscle cramps, tetany
  • Chvostek's & Trousseau's signs
  • < 8.5 mg/dL
  • inadequate intestinal absorption, blood administration, ↓ PTH
Term
Trousseau's Sign
Definition
[image]
Term
Chvostek's Sign
Definition
Term
Acid-Base Imbalances
Definition
  • Normal arterial blood pH
    -7.35-7.45
    -obtained by arterial blood gas (ABG) sampling
  • Normal pCO2
    -35-45
  • Normal HCO3
    -22-26
  • Normal pO2
    -80-100
  • acidosis
    -systemic ↑ in H+ concentration
  • alkalosis
    -systemic ↓ in H+ concentration
Term
Acidosis & Alkalosis
Definition
  • pH determines acid-base status
    -PaCO2→respiratory component
    -HCO3-/BE → metabolic component
  • acid-base imbalances:
    -Metabolic Acidosis: ↓ HCO3- (↑ acid or ↓ base)
    -Metabolic Alkalosis: ↑ HCO3- (↓ acid or ↑ base)
    -Resp Acidosis: ↑ pCO2 (ventilatory depression)

    -Resp Alkalosis: ↓ pCO2 (alveolar hyperventilation)
Term
Metabolic Acidosis
Definition
  • Symptoms
    -Weakness, N/V, warm/flushed skin, HA
    -hyperventilation or Kussmaul's breathing to ↓ PaCO2 (compensation)
    -dysrhythmia, hypotension, coma
  • causes:
    -lactic acid (hypoxia), ↑ ketones (fat metabolism in DM), salicylate poisoning, starvation/protein malnutrition, ↓ renal blood flow (↓ H+ excretion), ↑ urea (renal failure), ↓ HCO3- reabsorption (renal failure), chronic diarrhea
  • Rx: Treat underlying cause, administer base
Term
Metabolic Alkalosis
Definition
  • Symptoms
    -confusion, ↑ reflexes, spasms, tetany, paresthesias, seizure, dysrhythmia & coma (altered cell depolarization)
  • causes
    -vomiting (CI- loss), N/G suction, diuretics, dehydration, ECF electrolyte alteration, ↓ HCO3- glomerular filtration, HCO3- containing antacids, hypochloremic (Cl leaves cell, H+ enters), hypokalemia (↑ renal H+ excretion)
  • Rx
    -replace Cl- or K+, NaCl for dehydration
Term
Respiratory Acidosis
Definition
  • Hypercapnea = alveolar hypoventilation
  • Symptoms
    -HA, restlessness, blurred vision, vasodilation, tremors, convulsions, coma
  • causes
    -resp depression, pulmonary disorders, airway obstruction, COPD, neuromuscular disorders
  • Rx: maximize ventilation

 

Term
Respiratory Alkalosis
Definition
  • Hypocapnea = alveolar hyperventilation
  • symptoms
    -dizziness, confusion, tingling, tachypnea, convulsions, coma
  • causes
    -hypoxemia, CHF, ↑ altitude, thyrotoxicosis, ASA intoxication, cirrhosis, sepsis, iatrogenic (mechanical ventilation)
  • Rx: minimize ventilation as appropriate
Term
Innate Immunity
Definition
  • (1st) epithelial barrier & (2nd) inflammation
  • cellular
    -macrophages
    -dendritic cells
    -NK lymphocytes
  • complement system
  • cytokines
    -mediate host defense
    -inflammatory response
    -recruit T and B cells
Term
Adaptive Immunity
Definition
  • antigen-specific response
  • provides specificity & memory
  • Cellular
    -T lymphocytes
          -CD4
          -CD8
  • Humoral
    -B lymphocytes
    -immunoglobins
  • Cytokines
Term
Neutrophils
Definition

o   AKA polymorphonuclear (PMN cells or segmental neutrophils

o   1st responder-immediate phagocytosis

o   Call for B/U (chemotaxis)

o   Initiate vasodilation &     capillary permeability

o   Ingest bacteria, dead cells, & cellular debris

o   Cells short-lived & incorporated into purulent exudate

Term
Eosinophils
Definition

o   Primary helminthic (parasitic) defense

o   Minor phagocytosis

o   Regulate vascular mediators released from mast cells

§  Mast cells release ECF-A à attracts eosinophils to site of inflammation

§  Eosinophilic enzymes degrade vasoactive molecules (e.g. histaminase to degrade histamine)

Term
Basophils
Definition
  • release histamine, bradykinin & serotonin
    -↑ capillary permeability
    -↑ blood flow to injury site
  • secrete heparin (anticoagulant) as check to coagulation cascade
  • functional similarity to mast cells, but circulate in blood
  • source of cytokine IL-4 (regulator of acquired immune response via B-cell differentiation)
Term
Monocytes & Macrophages
Definition
  • circulate in blood
  • arrive at scene after neutrophils (hrs-7days)
  • in tissue, monos mature into macrophages
    -ingest cell debris/bacteria
  • macros produce cytokines (suppress further inflammation & initiate healing) & activate adaptive immune system
Term
Lymphocytes: B & T cells
Definition
  • circulate as inactive until activated by specific molecules per genetic program
  • B cell lymphocytes
    -mature in bone marrow
    -Humoral immune system - circulate in blood → plasma cell mounts immune response
  • T cell lymphocytes
    -mature in thymus gland
    -cellular immune system
    -may release chemicals to activate humoral response
    -stimulate (pro) or inhibit (anti) inflammatory cytokines
    -destroy intracellular viruses/parasites where B cells don't go
Term
NK cells
Definition
  • produced in bone marrow, maturation unclear, circulates in blood
    -present in blood and tissues
  • Non-specific innate defense
    -unlike T cytotoxic cells, do not require previous exposure to antigen
  • recognize & destroy cells injured by viruses or cancer
Term
platelets
Definition
  • cytoplasmic fragments in bone marrow
  • adhere to vessel wall at injury site in aggregates or clumps
  • release biochemical mediators (e.g. histamine, serotonin) to ↓ blood flow & bleeding - temporary vasoconstriction
  • small injury -  aggregation allows healing
  • circulation time ~ 10 days
  • ↓ platelet count → multiple small hemorrhages throughout body
Term
3 responses
Definition
[image]
Term
Epithelial Barrier
Definition
  • physical & mechanical
    -skin
    -linings of GI, GU, & respiratory tracks
          -sloughing of cells (turnover), coughing/sneezing, flushing,
              vomiting, urination, mucus & cilia
  • Biochemical
    -saliva, tears, earwax, sweat, mucus, & sebum
    -antimicrobial peptides (active cells of immunity)
            -cathelicidins, defensins, & collectins (lung)
Term

Biochemical Barriers

(part of 1st line of defense)

Definition

  • normal bacterial flora
    -aid digestion & absorption
    -produce Vitamin K & chemicals to inhibit pathogenic colonization
    -altered by prolonged antibiotic Rx
             -Clostridium difficile & Candida albicans overgrowth
             - ↓ vaginal protection from Lactobacillus
Term

Inflammatory Response

 

Definition
  • diverse causes; nonspecific (independent of stimulus/insult or past exposure)
  • act at site of cellular injury to:
    1. confine damage
    2. kill microorganisms
    3. remove debris
         -can be painful & harm healthy tissue
  • vasodilation (redness & heat), ↑ vascular permeability & leakage (edema), WBC adherence to inner vessel walls & migration through vessel walls to injury site (diapedesis)
  • cardinal "signs" of inflammation
    -redness, heat, swelling, pain (local)
    -fever, leukocytosis, plasma protein synthesis (systemic)
Term
phases of inflammation
Definition
[image]
Term
Acute Inflammatory Response
Definition
[image]
Term
Chronic Inflammatory Response
Definition
[image]
Term
Plasma Protein Systems
Definition
  • Protein systems
    -complement system (potent defense)
    -clotting system
    -kinin system
  • all contain inactive enzymes (proenzymes)
    -sequentially activated
    -produce potent substrates that are regulated to avoid damage to healthy tissue
Term

Complement

(Plasma Protein System)

Definition
  • direct pathogen destruction
  • activates or collaborates with other inflammatory response components
  • pathways
    -classical (Antigen-antibody complex, protein C1, substrate conversions)
    -Lectin (antibody-independent)
    -alternative (B/U with endotoxin & yeast)
  • Functions: anaphylatoxis (mast cell degranulation), leukocyte chemotaxis, opsonization (Tag! you're it- tag pathogenic micro orgs for phagocytosis), & cell lysis
Term

Clotting

(Plasma Protein System)

Definition
  • forms fibrinous meshwork at site of injury
    -prevents spread of infection
    -keeps micro orgs & foreign bodies at site of inflammation for phagocytic removal
    -forms clot that stops bleeding
    -provides framework for repair & healing
  • main substance is fibrin (end product of clotting cascade)
  • intrinsic & extrinsic pathways
    -converge at factor X → common pathway to fibrin clot
Term

Kinin

(Plasma Protein System)

Definition
  • activates inflammatory cells
  • bradykinin - primary
    -dilates vessels (vasodilation)
    -with prostaglandins, stimulates nerve endings (pain)
    - ↑s vascular permeability & leukocyte chemotaxis
  • rapidly degraded by plasma & tissue enzymes
Term

Plasma Protein Systems

(Clotting & Kinin)

Definition
[image]
Term
cellular mediators of inflammation
Definition
  • cellular components (blood and/or tissues)
    -granulocytes, monocytes, lymphocytes, & platelets
    -secrete & respond to biochemical mediators
  • immune cell surface receptors
    -pattern recognition receptors (PRRs)
             -host-environment interface (e.g. skin, GI tract)
             -toll-like, complement, scavenger, etc. receptors
                       -on surface of immune cells; others are secreted
                       -bridge bt innate & acquired immunity via cytokine induction
                            (↑ lymphocyte response to pathogen)

    -pathogen-associated molecular patterns (PAMPs)
Term
Mediators of Inflammation
Definition
  • vasodilation: histamine, NO, prostaglandins
  • vascular permeability: bradykinin, histamine, leukotrienes, platelet-activating factor (PAF)
  • pain: bradykinin, prostaglandins (E series)
  • systemic effects:
    -fever: IL-1, IL-6, TNF-α, prostaglandins
    -leukocytosis: granulocytes (G-CSF), leukocytes (IL-1, TNF-α), mast cells/eosinophils (IL-4, IL-5), monocytes (M-CSF), NK (IL-2)
    -acute phase reactants: C-RP, IL-1, IL-6, IL-8, TNF-α
  • limit inflammation:
    -ECF-A (attracts eosinophils)
    -histaminase (destroy histamine)
    -IL-10 (inhibits cytokine production)
    -TGF-β (inhibits macrophage proliferation)
  • immune response: IL-1, IL-2, IL-4, IL-5, IL-6, IFN-γ
  • repair & healing: angiogenic factors (VEGF→stimulate endothelial & fibroblast growth), IFN-γ (interferon that activates macrophages), TGF-β (stimulates fibroblast growth)
  • phagocytosis: C5, IL-1, leukotrienes, & many more
Term

mast cells

(fig 6-9)

Definition
  • cellular bags of granules locaated in connective tissue close to blood vessels
    -skin, GI & resp tracts
    -contain biochemical mediators: histamine, chemotactic factors (e.g. ECF-A), cytokines (TNF-α, IL-4)
  • activation
    -physical injury, chemical agents, immunologic processes, & toll-like receptors
    -chemical release of potent chemicals
                -degranulation (immediate response) & synthesis of lipid-derived
                  inflammatory mediators (long-term response)
Term
Mast Cell Degranulation
Definition
  • histamine
    -vasoactive amine- ↑ blood flow by temporary, rapid constriction of large blood vessels & dilation of postcapillary venules
    - ↑ vascular permeability by retraction of endothelial cells lining capillaries
    -receptors:
              -H1 receptor (PRO-inflam→bronchial smooth muscle cells)
              -H2 receptor (ANTI-inflam→gastric mucosea parietal cells, induces secretion of gastric acid)
Term
(events before) phagocytosis
Definition
  1. production of adhesion molecules (selectins & integrins)
  2. margination(pavementing)-leukocyte adherence to endothelial cells
  3. diapedesis-emigration of cells through endothelial junctions
  4. chemotaxis- tissue invasion; cell movement along a cellular gradient
  5. recognition & attachment
  6. phagocytosis
Term
Steps of phagocytosis
Definition
  1. opsonization (tag, you're it!)- recognition of target & adherence of the phagocyte to it
  2. engulfment (endocytosis)- ingestion
  3. fusion with lysosomal granules within the phagocyte (phagolysosome)
  4. destruction of the target
  5. neutrophils (early), macros & lymphs (later)
Term
Inflammation: Local Manifestations
Definition
  • local inflam with ALL cellular injury
  • results from vascular changes & corresponding leakage of circulating components into tissue
    -heat (vasodilation & ↑ blood flow at site of injury)
    -redness (vasodilation & ↑ blood flow at site of injury)
    -swelling (accumulation of exudate[fluids & cells])
    -pain (pressure from exudate accumulation, prostaglandins & bradykinin)
Term
Inflammation: Systemic Manifestations
Definition
  • fever
    -caused by exogenous (pathogen-produced) & endogenous (e.g. IL-1 released from neutrophils & macros) pyrogens
  • leukocytosis
    -↑ # of circulating leukocytes
    -"left shift" in ratio of immature (bands) to mature neutrophils
  • ↑ plasma protein synthesis
    -acute-phase reactants (pro- or anit-inflam)
             -C-reactive protein, fibrinogen, ceruplasmin, complement components, etc.
Term
innate immune response
Definition
  • inflammatory response
    -rapid
    -nonspecific
    -short-lived
Term
adaptive immune response
Definition
  • slower
  • specific
  • long-lived, memory
  • antigens
    -"non-self" substances (bacteria, virus, fungi, parasite, pollen, toxin, vaccine, transfusion, transplantation)
  • antibodies (immunoglobins)
  • lymphocytes
  • phases
    -clonal diversity
    -clonal selection
Term
Humoral Immunity
Definition
  • B cell differentiation→circulating antibody binds to antigens via plasma cell→direct (inactivate microorganism) or indirect (activates inflammatory mediators that destroy pathogen)
  • protection against bacteria & viruses
Term
Definition
Term
Cell-Mediated Immunity
Definition
  • T-cell differentiation (T regulatory, cytotoxic T, or memory T)→direct (inactivates microorganism) or indirect (activates inflammatory mediators that destroy pathogen) or avoid attacking self (T regulatory)
  • protection against viruses & cancer
Term
active immunity
Definition
  • antibodies or T cells produced after either natural exposure to antigen or immunization
  • long-lived
Term
passive immunity
Definition
  • preformed antibodies or T lymphocytes are transferred from donor to recipient (e.g. placenta)
  • short-lived
Term
inappropriate immune response
Definition
  • allergy-exaggerated immune response against environmental antigens (e.g. hay fever)
  • autoimmunity- immune response directed against "self" (e.g. systemic lupus erythematosis [SLE])
  • alloimmunity- immune response against beneficial foreign tissue (e.g. transfusion, transplant rejection)
  • immune deficiency- response insufficient to protect host (e.g. AIDS)
Term
Recognition & response
Definition
  • required for a successful immune response
  • clusters of differentiation (CD)
    -originally used to describe proteins found on surface of lymphocytes
    -now a labeling system to ID family of proteins on many cells
Term
antibodies
Definition
  • also called immunoglobulins
  • produced by plasma cells
  • classes of antibody
    -IgG, IgA, IgM, IgE, & IgD
             -characterized by antigenic, structural, & functional differences
Term
Immunoglobulins G (IgG) & A (IgA)
Definition
  • IgG
    -most abundant class (80-85%)
    -transported across placenta
  • IgA
    -IgA1 predominantly in blood
    -IgA2 predominantly in body secretions (e.g. saliva, breast milk, resp secretions)
Term
Immunoglobin E (IgE)
Definition
  • Least concentrated of immunoglobulin classes in circulation
  • mediator of many common allergic rxns
  • defender against parasites
    -initiates inflam rxn to attract eosinophils
Term
Antigen Processing & Presentation
Definition
  • Antigens require processing & presentation by antigen-presenting cells (APCs)
    -dendritic cells, macrophages, B lymphocytes
  • for processing & presentation:
    -antigen must be appropriate type
    -lymphocytes must be prepared to recognize presented antigen
    -antigen must be presented appropriately
Term
Primary Response (priming the pump)
Definition
  • mechanism of vaccination
  • latent period after novel antigen exposure
    -B cell differentiation occurring
  • after 5-7 days, IgM antibody detected
  • IgG response ≤ IgM response follows
Term
Secondary Response
Definition
  • mechanism of vaccination
  • more rapid with larger antibody amounts
  • presence of memory cells, differentiation not required
  • IgM produced similarly to primary response, but IgG produced in greater amounts
Term
Definition
Term
cell-killing mechanisms
Definition
  • cytotoxic T lymphocytes
    -destroy virus or cancer cells
  • NK cells
    -complement cytotoxic T cells
  • Regulatory T cells
    -suppress proliferation steps of antigen recognition
Term
Helper T Lymphocytes
Definition
  • subsets
    -Th1 cells provide help in developing cell-mediated immunity
    -Th2 cells provide help in developing humoral immunity
    -differences based on cytokine production
Term
Hypersensitivity
Definition
  • altered immunologic response to antigen→disease/damage to host
    -allergy-deleterious effects of hypersensitivity to environmental (exogenous) antigens
    -autoimmunity- disturbance in immunologic tolerance of self-antigens
    -alloimmunity-immune response to tissues of another individual
  • mechanisms of types overlap
  • Histamine release
    -H1 (smooth muscle contraction→bronchospasm) & H2 (↑ gastric acid secretion, ↓ histamine release from mast cells & basophils) receptors
    -antihistamine
  • sensitixation against antigen needed
    -primary & secondary immune responses
  • immediate or delayed hypersensitivity
    -anaphylaxis (bee sting, penicillin allergy) most rapid & severe, immediate
              -systemic (itching, erythema, headache, vomiting, abdominal cramps, diarrhea, dyspnea, bronchospasm, laryngeal edema, vascular collapse
              -Rx: Epinephrine IV or subQ
Term
Hypersensitivity Type I
Definition
  • IgE mediated
    -mast cells
  • against environmental antigens (allergens)
  • examples: hay fever, food allergies
  • itching, urticaria, conjunctivitis, rhinitis, GI cramps or malabsorption, ↓ BP, bronchospasm
  • desensitization (blocking antibodies [e.g. IgG] complete with IgE)

 

Term
Hypersensitivity Type II
Definition
  • tissue-specific rxn
  • antibody (IgG or IgM) binds to specific tissue antigen on cell surface & activates complement cascade→cell membrane damage & lysis; phagocytosis (macrophages); other mechanisms
  • e.g. autoimmune hemolytic anemia, ABO-mismatched blood, Graves disease, SLE
  • manifestations tissue-dependent
Term
Hypersensitivity Type III
Definition
  • immune complex-mediated (antigen-antibody complexes formed in blood and deposited in vessel wall or extravascular tissue)
    -IgG or IgM
    -dynamic & heterogeneous complement activation→neutrophils & lysosomal enzymes→tissue damage
  • e.g. raynaud phenomenon, autoimmune hemolytic anemia, ABO-mismatched transfusion, SLE, serum sickness
Term
Systemic Lupus Erythematosus (SLE)
Definition
  • caused by deposition of immune complexes in various organs→inflammatory response→tissue damage
  • heterogeneous presentation
  • involves type II & III
  • symptoms vary pt to pt
    -fatigue, arthralgias, dermatologic complaints, nephropathy, CNS, cardiac, respiratory, GI
Term
Hypersensitivity Type IV
Definition
  • cell-mediated
    -mediated by T lymphocytes, not antibody
  • cytotoxic T lymphocytes (direct destruction) or Th1 cells (phagocyte recruitment→ROS & cell lysis)
    -e.g. acute graft rejection, TB skin test (positive in photo), poison ivy, metal allergies
Term
Bacterial Virulence & Infectivity
Definition
  • bacteria must have iron to multiply
    -siderophores (iron receptors)
  • presence of polysaccharide capsules
  • suppression of complement activation
  • bacterial proliferation rates can surpass protective response
  • Toxin production:
  • exotoxins
    -enzymes released during growth causing specific responses
    -immunogenic
             -antitoxin production
  • endotoxins
    -lipopolysaccharides contained in cell walls of G- organisms
    -pyrogenic effects
Term
Definition
Term
Definition