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42 Cards in this Set

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  • Back
Inflammation is
a protective response done by blood vessels to eliminate infections & debris
Causes of inflammation are whatever causes injury:
Infection –Trauma, radiation –Chemical Injury –Autoimmune Disorders –Tumors

**itis
Inflammation resolves with tissue repair
-inflamation resolves when stimulus is taken away

-Can repair to prior state –Can leave a scar –Can persist - BAD
•Persistent tissue damage, serious scarring
•Can accelerate atherosclerosis
•Can cause tumors
Kinds of Inflammation
•Acute –Begins almost immediately, lasts minutes to days –Neutrophils, vessel permeability resulting in protein-rich exudate, mast cells
•Chronic –Begins ~1 or more days later –Lymphocytes, macrophages, ± plasma cells
•Granulomatous –Variant of chronic inflammation –Aggregates of epithelioid histiocytes, giant cells, cd 4 lymphocytes
5 Clinical Signs of Inflammation
-what causes dolor
Rubor - redness (vasodilation and increased blood flow)
•Tumor - swelling (edema)
•Calor - warmth (increased blood flow and fever)
•Dolor - pain (bradykinin, substance P, PGE2)
•Loss of function (tissue injury)
Fever
•Temperature > 37.2oC (99oF). •Can have vasodilation or vasoconstriction. •Can have shivering (chills), sweating.
•Due to infection, hormones, drugs, mediated by certain cytokines (esp. IL-1, TNF-α).
•Changes temperature regulation set point in hypothalamus.
•Malignant hyperthermia.
•"Sell at 106" i.e. serious tissue damage at 104-106oF / 40-1oC. Often fatal at 108oF / 42.2oC
role of vessels in inflamation
-what to vessels do
-this leads to what?
-what seeps through, it contains what?
-forms what? which is what?
-or what?, from what?
-what else do vessels do?
-
-
•Small vessels, esp. venules, develop endothelial cell retraction leading to increased permeablility (causes gaps)
•Plasma (exudate) seeps through the gaps (contains immunoglobulins, complement, clotting factors, and other factors that regulate or promote inflamation or repair)
•Forms exudate - fluid rich in proteins (Ig, clotting factors, complement, etc.) –Specific Gravity > 1.015 –Protein content > 1/2 that of plasma –LDH >163 IU/L
•DDx - transudate (low specific gravity, protein, & LDH) from hemodynamic problems (fluid overloading as in heart failure or a pt that has gotten to much IV)
•Vessels also recruit inflammatory cells to site
Laboratory Signs of Inflammation
-bacterial vs. viral
-parasites
-other thing that can occur
serosnguineous;
Leukocytosis (increased WBC) with neutrophilia (lots of neurtophils make pus or suppurative acute inflammation
- acute inflammation - think bacterial infection
–Neutrophils can be depleted by severe infections (infants amd elderly) –Look for bands (immature neutrophils), too
•Leukocytosis with lymphocytosis - chronic inflammation - think viral or granulomatous infection
•Eosinophilia - parasitic infection, autoimmune, asthma/allergic, tumors
•Thrombocytosis or thrombocytopenia can occur

-lots of RBC making fluid red
Increased sedimentation rate is?
-sign of inflamation
Increased plasma fibrinogen, red cells clump, sink faster –Fibrinogen is an acute phase reactant –Nonspecific general indicator of disease (infections, autoimmune, metastatic tumor) –Also an index of activity of a known disease
•CRP (C - reactive protein)
Another acute phase reactant, like fibrinogen –Becomes abnormal faster than sedimentation rate –Can increase up to 1,000-fold –Mild increases in otherwise healthy subject can indicate increased risk of atherosclerotic changes
Other acute phase reactants
-SAA (serum amyloid A protein)
–Ceruloplasmin (copper binding protein)
Other markers for cellular injury in specific organs
-myocardial damage (as in infarct)
-liver injury / hepatitis
-non-specific
-liver biliary obstructive injury (also in other tissues like bone, intestine)
- muscle injury
- pancreatitis
Troponin -
•Transaminases - AST, ALT - (AST also present in other organs)
•LDH (also present in many tissues) (not as specific about which organ is injured)
•Alkaline phosphatase -
•CPK (creatine phosphokinase)
•Amylase & lipase
Vascular Changes in Inflammation
•Acute Inflammation causes?
-lasts?
-arteriolies.... causes?
-endothelial ____, causes what?
-too much NO can cause what
- Immediate Transient Response
•Lasts 15-30 minutes
•Vasodilation in arterioles –Erythema & warmth
•Endothelial (venular) cell junction contraction in venules –leak plasma, swelling, cell transmigration
•in small vessels,Due to NO , histamine, bradykinin, cytokines (mast cell mediators) seep through
-body wide vasodilation/septic shock
inflamation; hours later

-due to vascular...
-continued... due to ? can cause what
-what induces damage?
-what encourages cell migration?
•Delayed, Sustained Vascular Response
•Hours later, can last days
•Vascular endothelial junction disruption
•Continued increased permeability & dilation (plasma leakage until thrombosis and repair)
•Due to: –Direct vascular trauma (includes sunburn which can caus leakage for days) –Cytokines, neutrophil-induced damaged (degranulation), or other endothelial damage
-slowed blood flow in vessels due to dilation and flow of plasma from the (encourages cell migration)
Cells in acute inflammation
•Mast cells
•Neutrophils
•Endothelium
Mast cells
-receptors for what?
-secrete what
stain used to recognize
key initiator of immune response Activated by trauma, burns, etc.,
-IgE cross-linking, toxins, endogenous mediators
-not dependent on prior exposure
•Degranulate, secreting: –Histamine –TNF-α (activates nearly all cells associated with immunity, IL-4 –Chemokines –Proteases (tryptase) –Heparin
•Also secrete leukotrienes / prostaglandins
-methylene blue
Neutrophils/polys
Recruited to inflamed tissue by:
•Phagocytose bacteria & toxins by several receptors:

-kill by

-extracellular interactions
early and principal cellular mediators of acute inflammation

–Endothelial interactions (selectins, integrins, addressins, ICAM-1&2, VCAM-1, PECAM-1) –Chemotactic stimuli (Bacterial lipids & peptides, complement (C5a), leukotriene B4, chemokines IL8)

-–Complement (C3B –Mannose binding lectins –Antibodies

-•Phagosomes merge with lysosomes (degranulation)–Digestive enzymes, respiratory burst / free radicals

-lysosmoes degranulate at cell membrane and go into surrounding tissue
-can help digest extracellular organisms but can cause tissue damage
Resolution of Acute Inflammation
-Complete resolution
-Scarring
•if agent cant be cleared
•If neutrophils can be phagocytized but not destroyed
• (if agent is cleared)
•(permant damage if it kills tissue that cant be reformed like alveoli
-there is cntinula neutrophil migration and if Walled off, continued tissue damage & acute inflammation causes abscess
- progresses to chronic inflammation, often granulomatous
-
examples of chronic inflamation/granulomatous
Necrotic tissue, such as in a myocardial infarct, causes acute, then chronic inflammation, then fibrosis. Uric acid, a DNA metabolite, is at least one of the mediators of acute inflammation in an infarct. Precipitates of uric acid (and extensive acute inflammation) also are found in gout.
Cells in Chronic Inflammation
Lymphocytes (sometimes plasma cells too) •Macrophages •Sometimes eosinophils • •Fibroblasts and new vessels in tissue repair
Chronic Infections Can Persist,
Causing Continued Injury
-variant of macrophages
granulomas
-TB can reactivate years later –Persists in granulomas –Thick cell wall •Secondary & tertiary syphilis –Surface is poorly immunogenic –Secretes antigenic proteins •HIV –Directly infects T cells and macrophages of immune response
3 Defects in leukocyte function
Adhesion ––defective beta 2 integrins -> recurrent infections •Phagocytosis –abnormal membrane protein involved in docking and fusion (Phagolysosome doesn’t form) –Chediak Higashi Syndrome •Microbicidal activity – Defects in NADPH oxidase –Chronic Granulomatous Disease
Chemical Mediators of Inflammation
-Cause
-Can have effects on:
Cytokines –Small proteins –Chemokines
• chemotaxis or activation •Specific structure with nearby cystine –•Same cell that secreted it (autocrine) •Nearby cells (paracrine) •Cells throughout the body (endocrine)
Basic Important Cytokines:
-made by Macrophages, Mast cells, others and does
-•Prolonged systemic ...
-made by Macrophages
•Activates
-Causes
- Made by some types of
lymphocyte
-Activates
-Helpful in
TNF-α
- •Activates many cells, can cause apoptosis, fever
-TNF-α causes cachexia
–IL-1β
- B cells, CD4 T cells, endothelial cells • fever –Interferon γ s
•macrophages, other cell types
•viral infections
Complement

Results
Cascade of proteases •Amplify, mediate effects of immunoglobulins •Also activated by innate immune mechanisms and neutrophil proteases

-Chemoattraction of inflammatory cells –Opsonization (promoting phagocytosis by macrophages and neutrophils) –Vascular changes (vasodilation, permeability) –Membrane attack complex (forms hole in cell membrane)
Kinin System

-Kallikrein is activated by
-makes

-Kinins / Bradykinin induce:

-interactions bw
is activated by Clotting Factor XII (Hageman factor) or (in vivo) HMWK

•Kallikrein makes kinins (including Bradykinin)
• –Vascular changes (vasodilation, permeability, via NO and prostacyclin) –Pain
•There are interactions between kinin cascade, complement activation cascade, clotting cascade, & renin/angiotensin cascade.
•Clotting and inflammation are related and often happen together.
Arachidonic Acid Metabolites
•Crucial inflammatory mediators •Cyclooxygenase pathway * –Prostaglandins –Prostacyclins –Thromboxanes
•5-Lipooxygenase pathway –Leukotrienes
5 Systemic Effects of
Inflammatory Response
•Fever (or rarely, a low temperature) •Leukocytosis / Leukocytopenia, Bandemia –Bacterial - neutrophils –Viral - lymphocytes •Tachycardia (>90 beats / minute) •Tachypnea (rapid breathing, >20 / minute) •Metabolic / Lactic acidosis
Systemic Inflammatory
Response Syndrome (SIRS)

-Two or more of:
Fever (temp >38oC or <36oC) • Tachycardia (>90/min) • Tachypnea (>20/min) or PaCO2 <32 mm Hg • WBC >12,000 or <4,000 or bands>10%
Sepsis

PLUS
•Systemic Inflammatory Response Syndrome •Some also allow other criteria (altered mental state, unexplained hypoxia, lactic acidosis, oliguria)

•Documented infection (Gram stain, positive culture, etc.)
Severe Sepsis
- Sepsis plus organ dysfunction, hypoperfusion, or hypotension
Septic Shock
- Sepsis with hypotension not corrected by adequate fluids
Multiorgan Dysfunction Syndrome / Multiorgan Failure -
- Failure of more than one organ, requiring intervention (oxygen, dialysis, etc.) - This is the most severe in this sequence, and is often seen before death
Sequence of
Systemic Effects

Causes include
SIRS -Sepsis -Severe Sepsis- Septic Shock -Multiorgan Dysfunction Syndrome

TNF-α, IL-1β, other cytokines Complement activation Bradykinin / Histamine Nitric Oxide (NO) - main cause of shock Systemic effects of neutrophil mediators Bacterial toxins, LPS
Toxic Shock Syndrome
-Abrupt onset of:
-Can have
-Cause is
-This toxin is
Fever with chills • Vomiting and diarrhea • Muscle aches • Rash
-severe shock, multiorgan failure, death
-usually Staph. aureus with TSST-1 toxin
-a superantigen - causing a life-threatening short-circuit of the immune response by directly activating the T cell receptor in many T cells at once.
EDEMA
Caused by
Exudate if
transudate if
inflammatory conditions, tumors, or hemodynamic / osmotic factors
-inflammatory or neoplastic
-hemodynamic / osmotic
Dependent edema
Pulmonary edema
•Anasarca
Periorbital edema
Localized edema
•- legs or lower part of body. •- often from heart failure. - edema of the whole body. •- puffiness around eyes. •- ?area of infection, trauma, circulatory problem.
Renal failure & thyroid deficiency often cause
periorbital edema or anasarca.
Repair & Wound Healing•Repair after an inflammatory process can be:
–Complete - to a normal state
–Forming a scar at the site of inflammation
–Forming a cavity - usually in the brain or lung
Regeneration is
-–Stem cells
–Labile cells
–Stable cells
–Permanent cells
limited and cell type dependent
- Primitive cell type that can proliferate and can differentiate to mature cell type(s)
- Normally proliferate, but not necessarily a primitive cell type such as a stem cell.
- Can proliferate in response to injury etc., but does not do so normally. (Hepatocytes)
- Cannot proliferate. Mostly cannot be replaced if lost. (Neurons, cardiac myocytes
Fetal surgery heals without scarring b/c.
–Abundant matrix metalloproteinases (MMP) –No TGF-β
Problems in Tissue Repair
Process is slow –~20% strength in 2 weeks –~70-5% strength at most (after several months)
–Never as strong as normal tissue
•Too Much (2ary intention, infection, clin. setting): –Hypertrophic Scar, granulation tissue –Keloid (extends beyond site of injury) –Desmoid / fibromatosis
•Too Little (steroids, poor circulation, debilitation, malnutrition/vitamin deficiency, infection):
–Wound Dehiscence (opening of wound) –Cardiac Rupture after Infarct