Inflammation Flashcards
INFLAMMATION: PART 1
INFLAMMATION: PART 1
Inflammation is coordinated ________ and ________ response of the body to cell injury and cell death.
vascular and cellular
Does inflammation have protective (immune) or curative features?
Both
Inflammation initiates the healing process and is responsible for the removal of what?
- injurious agent
- cellular debris
Is inflammation the equivalent of an infection?
No, associate it with tissue injury
Can we heal and have a normal immune function without an inflammatory response?
No
What is a type of drug that reduces inflammation by being a “immune suppressive drug”?
Glucocorticoids
What are some pathologies where inflammation can “run amok”?
- RA, Lupus, or SLE
- Obesity
- Crohn’s Disease
- Type I Diabetes
- Asthma
- Cancer
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)
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
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
*What are the 5 Cardinal Signs/Symptoms of Inflammation?
- Erythema (redness)
- Heat
- Edema
- Pain
- Loss of Function
What events cause erythema?
Vasodilation and increased blood flow
What events cause heat?
Vasodilation and increased blood flow
What events cause edema?
Fluid and cells leaking from local blood vessels into the extravascular spaces
What events cause pain?
- Direct trauma
- Chemical mediation by bradykinins, histamines, serotonin
- Internal pressure secondary to edema
- Swelling of nerve endings
- 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.
What events are the hallmark of inflammation?
Vascular
- Vasodilation
- Vascular Permeability
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
INFLAMMATION: PART 2
INFLAMMATION: PART 2
What type of cells are involved in the inflammatory response?
WBC (Leukocytes)
- Neutrophils
- Monocytes/Macrophages
- Eosinophils
- Basophils
- Lymphocytes
What type of cells are the first responders and are recruited within minutes on an injury?
Neutrophils
- What directs the movement of neutrophils to an injury?
- What are some examples?
- Chemotaxis
- IL-8, C5a, fMLP, Leukotrine B4
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
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
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
