Vasodilation: - _________ diameter of the small vessels in the area of injury. - Brings more ___________ and _________ to the area. - Induced by _________ release from platelets and mast cells causing smooth muscle relaxation. - Explains ______ and _______ at site of injury.

- increased - plasma proteins and leukocytes - histamine - heat and redness

Increased Vascular Permeability: - Smaller arterioles become leaky or __________. - Allows for the passage of a protein and cell rich fluid (________) into the interstitial spaces (IS) - Also results in accumulation of blood in the area of dilation and stasis resulting in localized _______ at the site and allow for accumulation of ______ and _______ at site of injury.

- permeable - exudate - redness, platelets and neutrophils

- What directs the movement of neutrophils to an injury? - What are some examples?

- Chemotaxis - IL-8, C5a, fMLP, Leukotrine B4

Inflammation Flashcards by Chance Lee Cauble

INFLAMMATION: PART 1

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Inflammation is coordinated ________ and ________ response of the body to cell injury and cell death.

vascular and cellular

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Does inflammation have protective (immune) or curative features?

Both

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Inflammation initiates the healing process and is responsible for the removal of what?

injurious agent

- cellular debris

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Is inflammation the equivalent of an infection?

No, associate it with tissue injury

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Can we heal and have a normal immune function without an inflammatory response?

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What is a type of drug that reduces inflammation by being a “immune suppressive drug”?

Glucocorticoids

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What are some pathologies where inflammation can “run amok”?

RA, Lupus, or SLE
Obesity
Crohn’s Disease
Type I Diabetes
Asthma
Cancer

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What are factors leading to inflammation?

Infection
Trauma/damaged tissue (physical or chemical)
Tissue necrosis
Presence of foreign bodies
Immune reactions
Ischemia
Cancer
Chemicals
Physical Agents (heat/cold, radiation)

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What are the 3 goals of an inflammatory response?

) Inactivate injurious agents
) Break down and remove dead cells and other cellular debris
) Initiate tissue healing

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What are some key components of inflammation?

blood vessels
circulating blood cells
connective or interstitial tissue cells (fibroblasts, mast cells, and resident macrophages)
chemical mediators
specific extracellular matrix constituents, primarily collagen and basement membrane

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*What are the 5 Cardinal Signs/Symptoms of Inflammation?

Erythema (redness)
Heat
Edema
Pain
Loss of Function

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What events cause erythema?

Vasodilation and increased blood flow

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What events cause heat?

Vasodilation and increased blood flow

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What events cause edema?

Fluid and cells leaking from local blood vessels into the extravascular spaces

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What events cause pain?

Direct trauma
Chemical mediation by bradykinins, histamines, serotonin
Internal pressure secondary to edema
Swelling of nerve endings

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Is inflammation capable of destroying and damaging normal tissue?
What is the response to this?

Yes (collateral damage)

- Inflammation is TIGHTLY REGULATED to avoid excess tissue damage and spillover to normal tissue.

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What events are the hallmark of inflammation?

Vascular

Vasodilation
Vascular Permeability

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Vasodilation:

_________ diameter of the small vessels in the area of injury.
Brings more ___________ and _________ to the area.
Induced by _________ release from platelets and mast cells causing smooth muscle relaxation.
Explains ______ and _______ at site of injury.

increased
plasma proteins and leukocytes
histamine
heat and redness

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Increased Vascular Permeability:

Smaller arterioles become “leaky” or __________.
Allows for the passage of a protein and cell rich fluid (________) into the interstitial spaces (IS)
Also results in accumulation of blood in the area of dilation and stasis resulting in localized _______ at the site and allow for accumulation of ______ and _______ at site of injury.

permeable
exudate
redness, platelets and neutrophils

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INFLAMMATION: PART 2

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What type of cells are involved in the inflammatory response?

WBC (Leukocytes)

Neutrophils
Monocytes/Macrophages
Eosinophils
Basophils
Lymphocytes

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What type of cells are the first responders and are recruited within minutes on an injury?

Neutrophils

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What directs the movement of neutrophils to an injury?

- What are some examples?

Chemotaxis

- IL-8, C5a, fMLP, Leukotrine B4

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What is diapedesis in regards to neutrophil movement?

Migration of blood cells through the endothelial lining of blood vessels (in response to inflammation)

What is the predominant cell type found in "pus" and in the area of injury for about 24 hours?

neutrophils

What type of WBC circulates in the blood and replenishes resident macrophages by differentiation?

Monocytes

What type of WBC engulfs and digests debris, foreign substances, mibrobes, and cancer cells? It is found in blood as mature and immature cells (monocytes).

Macrophages

What are some tissue specific macrophages?

- Langerhans- skin - Kupffer cells- liver - Alveolar macrophage - Microglia- CNS

What type of WBC produces antibodies?

Lymphocytes

What cell type plays a key role in the inflammatory process and contains large granules which hold several preformed immune mediators such as histamines, serotonin, thromboxane, prostoglandins, leukotrine, platelet activating factor, and TNF alpha.

Mast cells Think antihistamines!

Inflammation has a lot of complex processes. How are they controlled?

- Pro-inflammatory signaling molecules | - Anti-inflammatory signaling molecules

The inflammatory response occurs ________ to terminate infection. It also must halt in a timely manner to stop this reaction from inflicting _____ damage.

- rapidly | - self damage

What is the pathology of RA?

-Synovial cell multiply in number, influx of leukocytes from the peripheral circulation and synovium becomes edematous

In RA, TNF increases to cause a _______ inflammatory response. This attracts leukocytes, monocytes, and lymphocytes which phagocytize the immune complexes. This causes the release of _____________ which degrades cartilage as well as inhibits bone formation and stimulates bone resorption. Results in a structure called the _______.

- massive - metalloproteases - pannus

TNF is a cytokine central to many aspects of the inflammatory response and is secreted by _________, ____ cells, and _-__________.

- macrophages - mast - T-lymphocytes

What are a few examples of Anti-TNF compounds to moderate inflammation?

- Adalimumab (Humira) - Etanercept (Enbrel) - Infliximab (Remicade)

What are some Non-TNF boilogics to moderate inflammatory response?

- Tocilizumab (Actemar) | - Anakinra (Kineret)

Why are patients receiving anti-inflammatory drugs at increased risk for developing a serious infection and are tested for the presence of TB?

Glucocorticoids are immune suppressive

What are some systemic effects of acute inflammation?

- Fever - Somnolence, malaise - Anorexia - Hypotension - Accelerated degradation of skeletal muscle - Reflect increases circulating levels of IL-1, IL-6, TNF

- What is an increase in WBC count called? | - What is normal WBC count?

- Leukocytosis | - 4000-10000 cells/ul

What is a decrease in WBC count called?

-Leukopenia

INFLAMMATION: PART 3

Is inflammation a positive or negative feedback system?

positive feedback system

- Pro inflammatory signaling molecules are involved in controlling inflammation. These molecules have ______ half-lives and are rapidly degraded. - Large concentrations of pro-inflammatory signaling molecules leads to a reduction in amount of pro-inflammatory signaling molecules (__________ feedback system).

- short | - negative

Cells producing pro-inflammatory molecules produce and secrete "___________" or anti-inflammatory cytokines.

Stop Signals | -IL-4,10,11,13 and TGF-beta (macrophages)

As inflammation slows, what begins?

tissue repair

M1 macrophages ________ inflammation. They are first on the scene.

encourage (pro-inflammatory)

M2 macrophages are _____-inflammatory and encourage what?

- anti-inflammatory | - tissue repair

What are some neutrophil pathologies?

- deficits in numbers (neutropenia) - failure of neutrophils to respond to chemotactic stimuli - defects in the leukocyte adhesion molecules or the endothelial adhesion molecules - inability of neutrophils to move to injury site - failure of neutrophils to phagocytize properly - defective microbial killing

Inflammation: Summary - __________ - Increased vascular ____________ - Accumulation of __________ and cells all contributing to the destruction of “bad guys” - _________ damage is part of the process - Plethora of signaling compounds involved in initiating the inflammatory process and “Winding down” of the inflammatory process

- vasodilation - permeability - neutrophils - collateral

What are some possible outcomes of an inflammatory episode?

- complete resolution - abscess formation - healing by fibrosis or scarring - progression to chronic inflammation

If there is complete resolution of an inflammatory episode, will there be any damage to the connective tissue framework or non-recoverable cells of any part of the body? Will normal function return as well as a clearance of injurious stimuli?

- No, there will be no damage to the frameworkor cells | - Yes, normal function will return and injurious stimuli will be cleared

If there is abscess formation, there is an accumulation of pus in a _________ space that often requires draining.

confined

If there is healing by fibrosis (scarring) preinjury tissue is replaced by _________ tissue. In scarring there is a lack of __________ cells that make up the functional parts of an organ and are required for normal recovery from an injury.

- connective tissue (fibrotic) | - parenchymal cells

What are the implications of inflammation for the therapist?

- Does damage healthy tissue - Carries with it systemic effects - Therapists seek to limit (RICE, OTCs) - Return to play - Can lead to chronic inflammation

INFLAMMATION: PART 4

- When does progression to chronic inflammation occur? | - What is chronic inflammation characterized by?

- Happens when, and only when, the neutrophils and -their fast-acting molecular allies cannot remove the noxious agent. - Characterized by continuous tissue injury with ongoing attempts at repair.

What can chronic inflammation arise from?

- Persistent infections or presence of foreign particles - Hypersensitivity diseases - Prolonged exposure to toxic agents (silca, cholesterol, cigarette smoke, some cancers, etc.)

The hallmark of chronic inflammation is the tissue is infiltrated by _________, _________, and __________ (antibody producing cells) while there is an absence of ___________.

- macrophages - lymphocytes - plasma cells -neutrophils

Attempts at healing in chronic inflammation results in ___________ and _________.

- angiogenesis (growth of blood vessels) | - fibrosis

What is a form of chronic inflammation that is caused by aggregation of macrophages?

Granulomatous Inflammation

Acute vs. Chronic Inflammation: Onset - Acute = __________ - Chronic = ____________ Cellular Infiltrates - Acute = _____________ - Chronic = _____________ Tissue Injury, Fibrosis - Acute = ____________ - Chronic = ____________

Onset - Acute = fast- minutes to hours - Chronic = days Cellular Infiltrates - Acute = neutrophils mainly - Chronic = monocytes/macrophages and lymphocytes Tissue Injury, Fibrosis - Acute = usually mild and self limited - Chronic = often severe and progressive

Describe chronic inflammation in Diabetes.

- Increased activity of pro-inflammatory cells (macrophages) - Increased release of pro-inflammatory signaling molecules into the blood stream - These signaling molecules interfere with insulin signaling (GLUT-4) and damage pancreatic beta cells - Results in diabetes (Type II)

Describe chronic inflammation in Cancer.

- Tumor becomes a site of chronic inflammation and pro-inflammatory marker production - Tumor cells secrete pro-inflammatory markers

What are some drugs that can control pro-inflammatory state?

- Aspirin | - Celebrex

Pro-inflammatory state is ______ wide.

system

- Can cigarette smoke induce a chronic inflammatory state? | - What about smokeless tobacco?

- Yes | - Yes

Increased levels of what are associated with an increased risk for CV events?

C-Reactive Protein (CRP)

Heart disease is increasingly viewed as an ____________ disease.

inflammatory

Inflammation Flashcards

(70 cards)