Day 2: (TEXT)

Question 1

Increase in total number of white blood cells

Answer 1

Leukocytosis

Question 2

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?

Answer 2

acute appendicitis
CT

rebound tenderness indicates peritonitis

Question 3

Most common cause for acute appendicitis? Other

Answer 3

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

Question 4

Define inflammation

Answer 4

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:

1. The initial cause of cell injury (microbes, toxins)
2. Consequences of such injury (necrotic cells and tissue)

Question 5

What are three main mediators of inflammation?

Answer 5

Phagocytic leukocytes, antibodies, and complement proteins

Question 6

What are the five R’s of inflammation?

Answer 6

Recognition of injurious agent
Recruitment of leukocytes
Removal of the agent
Regulation of the response
Resolution/repair

Question 7

What are the components of the innate immune response?

Answer 7

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.

Question 8

What are three mechanisms we use to recognize microbes?

Answer 8

Cellular receptors for microbes-TLRs, Fc receptors

sensors of cell damage - cytosolic receptors

circulating proteins - complement system, mannose-binding lectin

Question 9

What are three major components of acute inflammation?

Answer 9

1. dilation of small vessels -> increased blood flow
2. increased permeability -> plasma proteins and leukocytes leave circulation
3. emigration of leukocytes from microcirculation -> accumulation in area of injury -> leukocyte activaiton

Question 10

Define exudation?

Answer 10

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

Question 11

Define: transudate

Answer 11

ultrafiltrate of blood plasma produced as a result of altered osmotic or hydrostatic pressure
NO increase in vascular permeability

Question 12

What induces vasodilation and what follows?

Answer 12

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

Question 13

What is stasis? Why does it occur?

Answer 13

Vasodilation and loss of fluid -> slower blood flow and increased viscosity
Stasis – engorgement of small vessels with slowly moving red cells

Question 14

How do we have increased vascular permeability because of histamine and other vasoactive mediators? Is this slow or rapid?

Answer 14

Contraction of endothelial cells resulting in increased interendothelial spaces

immediate transient response: 15-30 minutes?

Question 15

Lymphangitis

Answer 15

lymphatic vessels can become secondarily inflamed

Question 16

Lymphadenitis

Answer 16

draining lymph nodes may become inflamed and hyperplastic

Question 17

What are three steps of leukocyte recruitment?

Answer 17

1. Within the vessel:
   
   • Margination – facilitated by stasis and altered hemodynamic conditions
   • Rolling – transient adherence and detachment
   • Stable adhesion
2. Migration across the endothelium and vessel wall
3. Migration in the tissues toward a chemotactic stimulus

Question 18

How do TNF and IL-1 influence leukocyte adhesion?

Answer 18

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

Question 19

What is necessary for stable adhesion?

Answer 19

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)

Question 20

“transmigration” or “diapedesis” :what is it? what mediates it?

Answer 20

Leukocyte migration through endothelium

Mediated by CD31 – endothelial adhesion molecule in the intercellular junctions

Question 21

Which leukocytes predominate in the beginning? Which do later (after 24 hours?)

Answer 21

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

Question 22

What are stop signals for inflammation that inflammation triggers?

Answer 22

Inflammation also triggers “stop signals”

Switch in arachidonic acid metabolite production
Proinflammatory leukotrienes -> antiinflammatory lipoxins

Anti-inflammatory cytokines (TGFβ, IL-10) produced by macrophages

Question 23

What are four morphologic patterns of inflammation?

Answer 23

serous, fibrinous, purulent, ulcers

Question 24

inflammation with exudation of cell-poor fluid into spaces created by cell injury, or into body cavities

Answer 24

serous inflammation

Question 25

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)

Answer 25

Fibrinous inflammation

Question 26

inflammation caused by bacterial infection, exudate composed of neutrophils, necrotic cell debris, and edema fluid

Answer 26

Purulent (suppurative) inflammation

Question 27

inflammation with local defect of the surface of an organ or tissue produced by sloughing of inflamed necrotic tissue

Answer 27

ulcers

Question 28

What is the acute phase reaction? What are three important cytokines?

Answer 28

Inflammation (even localized) is associated with cytokine-induced systemic reactions = “acute phase response”

TNF, IL-1, IL-6

Question 29

What are four hallmarks of acute phase response?

Answer 29

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

Question 30

where are acute phase proteins produced? and what are they?

Answer 30

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

Question 31

What does ESR depend on? Through what method does does the acute phase change it?

Answer 31

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

Question 32

What is sepsis?

Answer 32

hypotension, DIC, metabolic abnormalities (insulin resistance and hyperglycemia) are induced by high levels of TNF and other cytokines