Inflammation And Infectious Diseases Flashcards
Inflammation
Body eliminated source of injury, removes damaged tissue, repairs itself
May contribute to disease
Cardinal signs of inflammation
Redness Swelling Heat Pain Loss of function
Inflammatory cells
Endothelium - Line blood vessels - Produce chemicals to maintain patently - Produce inflammatory mediators - Control migration of neutrophils Leukocytes
Types of WBCs
Neutrophils Lymphocytes Macrophages Eosinophils Basophils and mast cells
Neutrophils
Phagocytic
Secrete toxic oxygen
Arrive early
60%
Lymphocytes
B and T cells
Participate in adaptive immunity
Macrophages
Arrive within 24 hours
Clear tissue debris
Secrete cytokines, inflammatory mediators (leukotrienes, prostaglandins), and growth factors
6%
Eosinophils
Secrete mediators in response to allergies or parasites
3%
Basophils and mast cells
Secrete histamine and TNF
Inflammatory mediators
Originate from plasma or cells
- Plasma = complement and coagulation factors
- Cells = histamine, cytokines, etc
- Histamine
- Arachidonic acid metabolites
- TNF and IL
- Nitric oxide
- Oxygen free-radicals
Histamine
One of first mediators released
- Causes dilation or arteries
- Increases vascular permeability (temporary while leukotrienes are being manufactured)
Arachidonic acid metabolites
Cytokines formed from phospholipid in cell membranes
Arachidonic acid comes from cell membranes
Precursor molecule
Arachidonic acid metabolite pathways
COX pathway - create prostaglandins -> thromboxane -> recruit platelets
Lipooxygenase pathway - creates leukotrienes
Prostaglandins
Potentiate (makes more effective) histamine and induce inflammation
Leukotrienes
Take over for histamine More potent - ^ vasodilation - ^ vascular permeability - Attraction of inflammatory cells - Smooth muscle contraction
Omega 3 fatty acids
Alpha linolenic acid
Eicosapentanoic acid
Docosahexainoic acid
Anti inflammatory, blood thinning, artery dilation
Omega 6 fatty acids
Linoleic acid
Gamma linolenic acid
Arachidonic acid
Pro-inflammatory, promotes blood clotting, artery constriction
TNF and IL
Cytokines produced by macrophages, lymphocytes, endothelium, and other cells
- Induce endothelial cells to express adhesion molecules (selectins)
- Release other cytokines
- Release toxic oxygen
Induce acute-phase response of systemic inflammation
- Fever
- ^ HR
- v hunger
- ^ neutrophils
- ^ corticosteroids
Nitric oxide
Smooth muscle relaxation
Oxygen free-radicals
Increase expression of cytokines
Very reactive - can cause cellular damage
Acute inflammation
Immediate and localized
Components:
- Vascular changes
- Cellular changes
Vascular changes of acute inflammation
Transient vasoconstriction, then vasodilation
- Induced by histamine and nitric oxide
Increased vascular permeability follows
- Chemical mediators bind to endothelial cells, cause contraction, create gaps between endothelial cells
- Movement of protein rich fluid into extravascular space
- Increased osmotic pressure of extravascular space/interstitial tissue pulls fluid
Types of exudates
Serous - watery, yellowish fluids
Serosanguinous - some RBCs
Hemorrhagic (sanguinous) - leakage of RBCs
Fibrinous - contains fibrinogen (forms thick mesh)
Purulent - contains pus
Cellular changes
Changes in endothelium and movement of leukocytes into area of injury
Recruitment involves chemical mediators (mast cells)
Phases of cellular changes
Marination Adhesion Transmigration Chemotaxi Leukocytes activation Phagocytosis
Margination
Accumulation of leukocytes at site of injury
Adhesion
Cytokines stimulates endothelial cells to express adhesion molecules (selectins)
Bind to leukocyte (tethering)
Roll along endothelial lining
Come to rest and adhere to intracellular adhesion molecules - “firm adhesion”
Transmigration
Adhesion causes endothelial cells to separate
Leukocytes move between endothelial cells into tissue spaces
Chemotaxis
Movement of leukocytes to site of injury directed by chemokines
Leukocyte activation
Chemicals at site of injury
Phagocytosis
Recognition and adherence
- Depends on type of cell - recognized by receptor or opsonization
Engulfment
- Binding triggers endocytosis
Intracellular killing
- Phagosome merges with lysosome to destroy pathogen
Chronic inflammation
Infiltration of macrophages and lymphocytes rather than neutrophils
Fibroblasts instead of protein rich exudates
Often caused by persistent infection or irritants that don’t spread rapidly
More B and T cells than macrophages
Non-specific chronic inflammation
Diffuse accumulation of these cells
Granulomatous chronic inflammation
Constantly release chemical to try and eliminate pathogens
Associated with foreign bodies and some microorganisms
Systemic inflammation
Systemic response from release of inflammatory mediators into circulation
Acute phase response of systemic inflammation
Begins hours-days
Triggered by IL and TNF
Affect thermoregulatory system to create fever
Stimulate bone marrow to create neutrophils
Lack of appetite, sleepiness, aches by CNS response
Can lead to SIRS
Lymphadenitis
Inflammatory mediators produced by inflammation cause reaction when drained into lymph nodes
Painful, palpable nodes
Tissue repair processes
Tissue regeneration
Fibrous tissue repair
Tissue regeneration
Replacement of damage tissue with the same cell type: Parenchyma cells - functional - Recreation won't leave a scar Stromal cells - supportive - Will leave a scar
Capacity for regeneration
Varies by cell type
Labile - constantly regenerate (skin)
Stable - stop dividing, but can regenerate if signaled to do so (liver)
Permanent - do not regenerate (heart)
Fibrous tissue repair
Replacement of damaged tissue with connective tissue
Occurs with severe or repeated injury to parenchyma and stromal tissue
- Generation of granulation tissue
- Moist, red connective tissue
- Angiogenesis from existing vessels
- Foundation of new tissue
Fibrogenesis
- Influx of fibroblasts laying down loose ECM made of fibronectin, hyaluronic acid, and proteoglycans
- Proteoglycans (hydrophilic) are responsible for swelling
Scar formation
- Fibroblasts increase synthesis of collagen
- Vessels in granulation tissue degenerate
- Mature scar develops
Wound healing
Primary intention - Sutured wound - Faster Secondary intention - Pressure ulcer, burn - Slower - Granulation tissue develops, heals on outside, works towards middle - Prone to infection Approximating wound - taking edges and stitching together - Heals bottom-up
Phases of wound healing
Inflammation
- Preps wound for healing
- Vasoconstriction followed by vasodilation
- Influx of neutrophils and macrophages
Proliferative
- 2-3 days of injury
- Fibroblasts create granulation tissue, collagen, ECM
- Release growth factor that stimulate angiogenesis
- Epithelial cells are produced at wound edges
Remodeling
- 3 weeks after injury
- Structure of scar changes
- Vascularity decreases
- Generation of collagen by fibroblasts
- Lysis of collagen by enzymes
- Wound contraction results in shrinkage of scar
Mechanisms of infectious diseases
Prions - Protein particles - mutation of normal host protein - Cause non-inflammatory degeneration of neurons - Creutzfeldt-Jakob and Mad Cow disease Viruses - Made of protein coat and nucleic acid code - Can't replicate outside of living cell - May insert itself into genome of host cell Bacteria - Unicellular organisms - No organized nucleus - High adaptable Fungi - Organized nucleus - Yeasts, molds Parasites - Derive benefit from host - Unicellular or multicellular - Protozoa (giardia lamblia) - Helminths (ascaris) - Arthropods (ticks, fleas)
HIV
Malignancy
Body wasting
CNS degeneration
Reproduction of HIV
Retrovirus - has RNA and creates DNA
- Binds with host cell and inserts itself into DNA
- Reverse transcriptase makes DNA from RNA to make a double strand of DNA
- Viral DNA incorporates itself into CD4 cell
- DNA is read and creates nucleic acids and protein coats
- Creates virus and destroys CD4 cell
Transmission of HIV
Blood to blood contact or perinatally
Infected blood, semen, or vaginal secretions come into contact with mucous membranes or bloodstream of another
Window period
When an infected person can pass the virus in the absence of symptoms
Seroconversion
Positive presence of HIV antibodies in blood
- Characterized by CD4
- Count <200 is AIDs
Rickettsiaceae and Chlamydiaceae
Combine characteristics of viruses and bacteria
- Cannot replicate outside of host cell
- Produce rigid cell wall, reproduce asexually, contain DNA and RNA
Depend on host cell for nutrients
Rickettsiaceae from arthropod bite and Chlamydiaceae transmitted directly
Stages of infection
Incubation - pathogen replicating slowly, no symptoms in host
Prodromal - initial appearance of symptoms
Acute - max. replication of pathogen and symptoms, inflammatory/tissue damage occurring
Convalescent - containment, tissue repair, resolution of symptoms
Resolution - total elimination
Host defenses
Secretions in mucosal membranes
Lysozyme in tears dissolve peptidoglycan in bacterial wall
Skin
- Low pH and presence of fatty acids
- Maceration - when skin shrivels on itself
GU tract
- Sterile
Respiratory tract
- Mucociliary blanket lining nose and upper resp. tract trap microbes
- Goblet cells secrete mucous
- Cilia in upper airway move bacteria to back of throat to swallow/expel
- Alveolar macrophages destroy small organisms
GI tract
- Gastric acid
- Viscous mucous layer coats gut
- Pancreatic enzymes and bile
- IgA secreted by mucous membranes
Factors enhancing virulence
Toxins
Adhesion factors
Evasive factors
Invasion factors
Exotoxins
Proteins released by bacteria during growth
- Enzymatically alter components of host cell -> dysfunction or death
Endotoxins
Lipid and polysaccharide in cell wall of G- bacteria
Adhesion factors
Special filaments that enable pathogens to attach to host
Evasive factors
Means by which pathogens avoid immune system of host
- Capsules, chemical release, ability to survive within leukocytes
Invasive factors
How pathogens invade host
Antimicrobial resistance
Associated with extended hospitalization, significant morbidity, increased mortality
Acquisition of resistance
Spontaneous mutation
- Random alteration in DNA
Conjugation
- Transfer of genetic material from one organism to another
How do bacteria resist antibiotics?
Reduced concentration of drug at site of action - Site is intracellular - Cease active uptake - Increase active export Alteration of drug target molecule - Cell receptors - Ribosomes Production of antagonist Inactivation of drug - Produce drug-metabolizing enzymes
Immunotherapy
Supplementing or stimulating immune system of host to limit spread of pathogen
- IV immune globulin (antibody given in IV to fight infection - not created by body)
- Cytokines
- Immunization
Active immunity
Developed by vaccination or having the disease
Body exposed to antigen and develops its own immunity
Immune system responds by creating antibodies
Passive immunity
Immunity from another
Fetus protected by IgG of mother
Hyperimmune serum
Blood vessel layers
Tunia intima - Remain smooth - Release cytokines and other inflammation factors - Maintains potency (openness) - Control migration of neutrophils Tunia media Tunia externa
SIRS
Systemic inflammatory response syndrome
- Vasodilation
- BP plummets, difficult to get blood to the brain
- ^ HR as compensation
- Body constricts vessels to less important areas
