Pathology Chapter 3

What are the two phases that occur during acute inflammation and what do they involve?

(1) vascular phase -leads to an increase in blood low and changes in the small blood vessels of the microcirculation (2) cellular phase - migration of leukocytes from the circulation and their activation to eliminate the injurious agent.

During vascular stage of acute inflammation, what leads to the clotting of blood?

- as fluid moves out of the vesselsdue to increased capillary pressure--> stagnation of flow in interstitial space-->causes blood clot

Redness

- due to increased blood flow during vasodilation ( No, histamine)

Chronic inflammation

- longer duration,( lasting for days to years) -associated with the proliferation of blood vessels (angiogenesis), tissue necrosis, and brosis (scarring)

• Mast cells

- mediate inflammatory responses (ie allergic reactions) -scattered throughout connective tissues, beneath skin, near blood vessels & lymphatic tissues, in resp, digestive & urinary tracts -store number of different chemical mediators in vesicles

What purposes does the inflammation response provide?

-Neutralizes harmful agents -Removes damaged & dead tissue (of your own or the bacteria's & virurses that enter your body) -Generates new tissue Promote healing- -regrow/repair tissue

What kinds of cells are involved in the cellular response during acute inflammation?

-Neutrophils -basophils (while in blood vessels), Mast cells (while in tissue) -eosinophils -monocytes -macrophags -lymphocytes -platelets

Acute inflammation is characterized at the cellular level by ...

the exudation of fluid and plasma proteins -emigration of leukocytes

Explain what happens in the extravascular tissues local to the injury concerning leukocytes during acute inflame

- leukocytes leave vasculature through: 1) Maringation- line up along endothelial surface, adhere to adhesion molecules on endothelial cells 2) activation/ adhesion 3) transmigration

Endothelial cells

-make up single- cell thick linings of blood vessels - help separate the intravascular & extravascular spaces -nothombogenic surface -produce agents that maintain vessel potency, vasodilators & vasoconstrictors (regulate blood flow -key player in inflammatory response

what are Basophils ? & what do they release during acute inflammation? (4)

-mast cells in the tissues -contain chemicals of inflammation a) Histamine- blood vessel dilation b) Protease- get rid of protein bact. Cell mem c) Heparin- makes blood thin, so it can flow better, make viscosity of blood lower so platelets and WBC can reach site faster d) Tumour necrosis factor (TFN)- can cause apoptosis w/in a cell

why are endothelial cells considered "key players" in the inflammatory response?

-selectively permeable barrier to exogenous (microbial) & endogenous inflammatory stimuli -regulate leukocyte extraction by

Chemical mediators stores by mast cells

A) interleukins (cytokines) - activate other nearby immune cells B) histamine: nearby blood vessels to dilate --> more permeable C) heparin: anticoagulant, preventing blood clot at that location. produce local responses characteristic of an allergic reaction, such as increased permeability of blood vessels (i.e., inflammation and swelling), contraction of smooth muscles (e.g., bronchial muscles), and increased mucus production.

Fever

Also known as pyrexia is an elevation in body temperature caused by upward displacement of set point of thermoregulatory centre in hypothalamus.

Define: inflammation

An innate, automatic response reaction of vascularized tissues to cell injury or death. -typically conditions with the suffix "itis"

• Relapsing fever

One or more episodes of fever, each as long as several days with one or more days of temperature between episodes. Caused by a variety of infectious diseases.

• Hemorrhagic exudate

Severe tissue injury that causes damage to blood vessels or when there is significant leakage of red cells from capillaries.

• Serous exudate

Watery fluids low in protein content that result from plasma entering the inflammatory site.

How does vessel flow change during acute inflam?

change in vessel flow due to N.oxide & histamine--> vascualr smooth muscle--> vasodil--> increased blood flow -slowed blood flow in local area, hyper viscosity -margination circulating leucocytes & enothelial activation

cellular stage

characterized by emigration of leukocytes (mainly neutrophils) from the microcirculation and accumulation at site of injury or infection

vascular stage

characterized by increased blood flow (vasodilation) and structural changes (increased vascular permeability)

How to mast cells respond during acute inflammation

contact with an antigen, the cell releases those chemicals into the surrounding tissue (exocytosis/degranulation) histamine: causes nearby blood vessels to dilate and become more permeable heparin acts as an anticoagulant, preventing the blood from clotting at that location.

What are the two first cardinal signs of acute inflammation ? why do they occur?

heat and redness Vasodilation involves the arterioles and venules--> increase in capillary blood flow immediately after injury incurred

Monocytes/macrophages

same functions as neutrophils arrive later longer lasting may form "giant cells"

• Plasma cells

short-lived antibody-producing cell derived from a type of leukocyte (cells) -B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell. - antibodies bind to target antigen --> neutralize it

Can acute & chronic inflammation co-exist? If so how?

they CAN episodes of acute in ammation being superimposed on chronic inflammation.

Acute inflammation

triggered by noxious stimuli, (infection or tissue injury) -rapid in onset (typically minutes), -short duration ( few minutes to several day)

During the vascular stage of acute inflammatory response why what occurs the larger vessels to help facilitate a response locally? (i.e. where injury occurs?)

vasoconstriction of larger local vessels - Same thing happens w. bigger vessels in body (femoral artery & aorta) you want these vessels to constrict so pressure will increase and send blood towards smaller, more local vessels

Lymphocytes

produce antibodies ( its not enough just to fight invading pathogen, description of criminal vs actual picture) or lymphokines cells of the immune system ex. B cells & T-cells

• Platelets role in inflammation

promote clotting, inflammation -bind together

Acute inflammation: Cellular stage

-cellular recruitment & activation of neutrophils (polymorphonuclear leukocytes)

T cells

-type of lymphocyte a) Cytotoxic t-cell-kills targeted cell (antigen presented by b-cell marcrophage ect) -kill infected cells (& cancer cells) by apoptosis b) Helper tequila: Help other cells by "telling" them how to eliminate pathogens Don't directly kill pathogen, send cytokines to other cells to tell them to kill

B-cells

-type of lymphocyte - involves production of antibodies -destory extracelllular pathogens - will bump pathogen and will display that piece on cell membrane) antigen presenting -->stimulates antibody production for intracellular pathogen -differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.

What do lymphocytes release?

1) Progaglandins- cause pain 2) Leukotrienes- tell other cells to come cell communication 3) Platelet activation factor (PAF)- in absence of platelet, you would continue to bleed

Role of neutrophils during cellular stage of acute inflammatory response

1. first phagocytes at the site (rescuers but just with shovels call for backup) 2. Phagocytose cell debris, bacteria BUT short-lived, die 3. are removed as pus trail left for other phagocytes (monocytes or macrophages) to follow

What is the primary functions of the acute inflammatory response?

1. limit the injurious effect of the pathologic agent 2.remove the injured tissue components -->thereby allowing tissue repair to take place.

During the vascular stage of acute inflammatory response why does vasodilation occur in the smaller vessels?

A) increasing blood flow to injured area- to accommodate for constriction of bigger vessels B) the more you dilate something, the more permeable so more cells can leave & facilitate a better immune response( inflate the vessels)

what happens after there is a change in vessel flow during vasodilation?

increased permeability of vasculature formation of an early transudate (protein-poor filtrate of plasma) gives way to exudate (protein-rich filtrate) into extracellular tissues

• Eosinophils

Act against parasites or when allergic reaction occurs control inflammation keeps at particular site -act against mediators such as histamine --> protects against anaphylactic shock

Why do the capillaries become more permeable during the vascular stage of acute inflammation?

Allowing exudate( protein rich fluid) to escape into the tissues facilitate a better immune response( inflate the vessels) so more neutrophils can enter to infected area from other site

What is the most common mechanism of vascular leakage/ increased permeability during acute inflammation?

Binding of the chemical mediators ( histamine, bradykinin, leukotrienes )to endothelial receptors in venules= separation of inter- cellular junctions & contraction of epithelial cells --> fluid leaks out

loss of function

Cardinal sign of inflammation

swelling

Cardinal sign of inflammation; abnormal enlargement of part of the body due to accumulation of fluid

heat

Cardinal sign of inflammation; increased temperature of part of the body

pain

Cardinal sign of inflammation; physical suffering or discomfort

• Fibrinous exudate

Contain large amounts of fibrinogen and form a tick and sticky meshwork, much like the fibres of a blood clot.

• Purulent exudate

Contains pus, composed of degraded white blood cells, proteins and tissue debris.

• Membranous exudate

Develop on mucous membrane surfaces and are composed of necrotic cells enmeshed in a fibropurulent exudate.

• Conduction

Direct transfer of heat from one molecule to another. Blood carries heat from inner core to skin surface.

• Convection

Heat transfer through the circulation of air currents. Causes continual removal of warm layer near body's surface and replacement with air from surrounding environment.

• Acute inflammation

Early or almost immediate reaction of local tissues and their blood vessels to injury and be triggered by a variety of stimuli. There are 2 stages; vascular and cellular

• Neurogenic fever

Fever with its origin in the central nervous system. Result of damage to the hypothalamus caused by central nervous system trauma. High temperature that is resistant to antipyretic therapy and not associated with sweating.

Why does vascular leakage & edema occur during acute inflam?

Histamines, bradykinins, leukotrienes cause endothelial cell contraction that widens intercellular gaps of venules - Outpouring of protein-rich fluid (exudate) into the extracellular tissues leads to: • Reduction of intravascular osmotic pressure • Increase in extravascular/interstitial osmotic pressure - Increase of interstitial osmotic pressure leads to edema (water and ions)

• Radiation

Involves transfer of heat through the air or a vacuum. Environmental temperature must be less than that of the body for heat loss to occur.

• Cell-derived mediators

Released from cells present at sites of inflammation. Tissue macrophages, mast cells, endothelial cells, leukocytes.

• Chronic inflammation

Self-perpetuating and may last for weeks, months and even years. Develop as result of recurrent or progressive acute inflammatory process. Characterized by infiltration with mononuclear cells and CT repair via angiogenesis and fibrosis.

• Remittent fever

Temperature does not return to normal and varies a few degrees in either direction.

• Core temperature

Temperature in the deep tissues of the body, 36.0 - 37.5

• Sustained fever

Temperature remains above normal with minimal variations. Seen in persons with drug-induced fever.

• Intermittent fever

Temperature returns to normal at least once every 24 hours. Commonly associated with conditions such as gram-negative/positive sepsis, abscesses and acute bacterial endocarditis.

What purpose does clotting of blood serve during the vascular stage of acute inflammation?

This aids in localizing the spread of infectious microorganisms.

• Plasma-derived mediators

Three major protein cascades: kallikrein-kininogen, coagulation system and complement system. Contribute to inflammatory response by vasodilation and increasing vascular permeability, promoting leukocyte activation, adhesion and chemotaxis and augmenting phagocytosis.

• Evaporation

Use of body heat to convert water on skin to water vapour. Water that diffuses through skin independent of sweating is insensible perspiration

During an acute inflammatory response, what happens during the VASCULAR stage to facilitate a response locally?

characterized by: 1) changes in small blood vessels at site of injury vasodilation (vasoconstriction of larger vessels) 2) increased adhesion of WBC 3) increased permeability of capillaries

What happens when when All large vessels constricted, small vessels dilated and blood flow is too high for platelets to be able to form a clot?

difficult for platelets to bind together so release serotonin to create local constriction only

The other cardinal signs of acute inflammation are swelling, pain & impaired function. What causes these?

due to fluid proteins flowing out into interstitial space to reduce capillary osmotic pressure (bc of vasodilation) = increase in interstitial pressure causes accumulation of fluid in the tissue spaces= symptoms

Neutrophils with polymorphous nucleus during Cellular response of acute inflammation

first to site only live ~ 8-9hr -once they are dead and/or body detects injury, body will produce more but often not enough time for these neutrophils to mature , they will still go an try to participate in fight, child soilders the polymorphous nuclues