Day 2: (TEXT) Flashcards
Increase in total number of white blood cells
Leukocytosis
periumbilical pain (referred) which localizes to McBurney’s point
Often associated with fever/N/V
Rebound tenderness -> pain upon removal of pressure rather than application of pressure.
What do you suspect? How do you diagnose?
acute appendicitis
CT
rebound tenderness indicates peritonitis
Most common cause for acute appendicitis? Other
most common: fecalith
others:
inflamed lymphoid tissue (viral infections, parasites), gallstones, tumors
Causes increased pressure within the appendix -> decreased blood flow -> bacterial growth -> inflammation -> tissue injury and death
Define inflammation
Response of vascularized tissues to infections and tissue damage
Mediators of host defense are recruited from the circulation to sites where they can eliminate the offending agents:
- The initial cause of cell injury (microbes, toxins)
- Consequences of such injury (necrotic cells and tissue)
What are three main mediators of inflammation?
Phagocytic leukocytes, antibodies, and complement proteins
What are the five R’s of inflammation?
Recognition of injurious agent Recruitment of leukocytes Removal of the agent Regulation of the response Resolution/repair
What are the components of the innate immune response?
epithelial barrier phagocytes: neutrophils, monocytes dendritic cells complement: natural killer cells:a lymphocyte able to bind to certain tumor cells and virus-infected cells without the stimulation of antigens, and kill them by the insertion of granules containing perforin.
What are three mechanisms we use to recognize microbes?
Cellular receptors for microbes-TLRs, Fc receptors
sensors of cell damage - cytosolic receptors
circulating proteins - complement system, mannose-binding lectin
What are three major components of acute inflammation?
- dilation of small vessels -> increased blood flow
- increased permeability -> plasma proteins and leukocytes leave circulation
- emigration of leukocytes from microcirculation -> accumulation in area of injury -> leukocyte activaiton
Define exudation?
escape of fluid, proteins, and blood cells from vascular system into interstitial tissue or body cavities
exudate: increased permeability of small vessels triggered by tissue injury and inflammation
Define: transudate
ultrafiltrate of blood plasma produced as a result of altered osmotic or hydrostatic pressure
NO increase in vascular permeability
What induces vasodilation and what follows?
Vasodilation is induced by several mediators (i.e. histamine) acting on vascular smooth muscle in the postcapillary venules
Followed by increased permeability -> outpouring of protein-rich fluid into tissues
What is stasis? Why does it occur?
Vasodilation and loss of fluid -> slower blood flow and increased viscosity
Stasis – engorgement of small vessels with slowly moving red cells
How do we have increased vascular permeability because of histamine and other vasoactive mediators? Is this slow or rapid?
Contraction of endothelial cells resulting in increased interendothelial spaces
immediate transient response: 15-30 minutes?
Lymphangitis
lymphatic vessels can become secondarily inflamed
Lymphadenitis
draining lymph nodes may become inflamed and hyperplastic
What are three steps of leukocyte recruitment?
- Within the vessel:
- Margination – facilitated by stasis and altered hemodynamic conditions
- Rolling – transient adherence and detachment
- Stable adhesion
- Migration across the endothelium and vessel wall
- Migration in the tissues toward a chemotactic stimulus
How do TNF and IL-1 influence leukocyte adhesion?
They improve initial rolling (low affinity)
TNF and IL-1 upregulate selectins on endothelial cells and their ligands on leukocytes (sialylated oligosaccharides)
Leukocytes slow down, but are easily disrupted by flowing blood
What is necessary for stable adhesion?
integrins on leukocytes binding to ligands on endothelial cells (VCAM-1, ICAM-1)
this is mediated by chemokines and cytokines (making the integrins have a high affinity state, and upregulating VCAM - 1 and ICAM -1)
“transmigration” or “diapedesis” :what is it? what mediates it?
Leukocyte migration through endothelium
Mediated by CD31 – endothelial adhesion molecule in the intercellular junctions
Which leukocytes predominate in the beginning? Which do later (after 24 hours?)
Neutrophils predominate in first 6-24 hours
More numerous in the blood, respond more rapidly to chemokines, attach more firmly to selectins
Short-lived: undergo apoptosis and disappear within 24-48 hours
Replaced by monocytes in 24-48 hours
Survive longer and proliferate in tissues, thus becoming dominant population
What are stop signals for inflammation that inflammation triggers?
Inflammation also triggers “stop signals”
Switch in arachidonic acid metabolite production
Proinflammatory leukotrienes -> antiinflammatory lipoxins
Anti-inflammatory cytokines (TGFβ, IL-10) produced by macrophages
What are four morphologic patterns of inflammation?
serous, fibrinous, purulent, ulcers
inflammation with exudation of cell-poor fluid into spaces created by cell injury, or into body cavities
serous inflammation
infalmmation with increased vascular permeability -> leakage of large molecules (fibrinogen);
caused by body cavity lining inflammation when vascular leaks are large or there is a local procoagulant stimulus (e.g. cancer cells)
Fibrinous inflammation
inflammation caused by bacterial infection, exudate composed of neutrophils, necrotic cell debris, and edema fluid
Purulent (suppurative) inflammation
inflammation with local defect of the surface of an organ or tissue produced by sloughing of inflamed necrotic tissue
ulcers
What is the acute phase reaction? What are three important cytokines?
Inflammation (even localized) is associated with cytokine-induced systemic reactions = “acute phase response”
TNF, IL-1, IL-6
What are four hallmarks of acute phase response?
constitutional symptoms: fever, anorexia, lethargy, rigors, chills
leukocytosis: cytokines stimulate production of luekocytes from precursors of bone marrow
elevated erythrocyte sedimentation rate (ESR)
CRP increases 100 - 1000 x
where are acute phase proteins produced? and what are they?
liver
C-reactive protein (CRP) and serum amyloid A (SAA) protein:
Bind to microbial cell walls, may act as opsonins and fix complement
Also bind chromatin – possibly aid in clearing necrotic cell nuclei
What does ESR depend on? Through what method does does the acute phase change it?
Sedimentation of RBCs depends in part on surface potential, the zeta potential: cells repel each other
Acute phase: fibrinogen binds to RBCs and reduces zeta potential, making RBCs sediment at higher (faster) rate
so ESR tells you that fibrinogen is doing things
What is sepsis?
hypotension, DIC, metabolic abnormalities (insulin resistance and hyperglycemia) are induced by high levels of TNF and other cytokines
