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Inflammation
- reaction of vascularized tissue to cell injury of cell death
- consider to be adaptive
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What is the function of inflammation?
- minimize effects of injuring agent
- isolate and limit damage to smaller area
- removes damaged cells/tissues and sets the stage for cell division and healing
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What happens if excessive or chronic inflammation occurs? Give an example.
- Can cause even more cell injury and cell death
- Seen in bronchial asthma
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Acute inflammation last a few minutes to a few days. It has two phases:
- Vascular phase: exudation of fluid and plasma
- Cellular phase: release of chemical mediators triggering specifics actions
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Chronic inflammation lasts anywhere from days to years. Commonly results in:
- abnormal proliferation of blood vessels, necrosis, and fibrosis
- damages cell
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Cells of inflammation: Tissue cells
- Fibroblats: connective tissue makes finers- collogen and elastin
- Mast cells: Histamine release for allergy or inflammation
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Cells of inflammation: Endothelial cells-
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Cells of inflammation: Leukocytes
Granulcytes or Aganulocytes
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What are the three types of granulocytes (BEN)?
Basophils, Eosinophils, Neutrophils
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What are the two types of Agranulocytes?
- Monocytes--->macrophages
- Lymphocytes and mature plasma cells
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Neutrophils are the phagocytes of _____ inflammation and Monocytes are the phagocytes of _____ inflammation.
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Eosinophils:
proteins that are toxic to parasitic worms
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Basophils:
histamine released in allergy response or inflammation
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Lymphocytes:
cell-mediated and anti-body mediated immunity
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What are inflammatory mediators? Name two types.
- A variety of chemicals in plasma that are released from cells with specific effects
- Cytokine and Chemokine
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Cytokine:
chemical mediator secreted by one cell that has specific effects on a different cell
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Chemokine:
- chemical mediators secreted by one cell that attracts a different cell type to a specific area
- Chemotaxis
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What is exudation?
- Occurs during inflammation process
- The movement of fluid, leukocytes, and proteins from the blood into the damaged area
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What can trigger acute inflammation?
Anything that damages or kills cells
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List the 5 cardinal signs of inflammation:
- Redness, swelling, heat, pain, loss of function
- Extra: systemic manifestations such as an altered WBC count, fever, etc
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Acute inflammation has two distinct, overlapping phases:
Vascular and cellular
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Vascular phase of Acute inflammation:
exudation of fluid and plasma proteins, from blood vessels into tissue
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During the vascular phase of inflammation, what aids in clotting?
As fluid leaves blood it causes a stagnation of blood flow that aids in clotting
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During vascular phase of inflammation, what causes vasoconstriction, followed by vasodilation?
- Histamine
- Nitric oxide
- some other chemical mediators
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During the vascular phase of inflammation, what aids in increased vascular permeability after vasoconstriction/vasodilation?
- Histamine,
- Bradykinin
- Leukotrienes
- activated complement proteins
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Cellular phase of acute inflammation:
release of chemical mediators, triggering specific actions by specific cells
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During the cellular phase of acute inflammation, chemotactic chemokines do what?
Attract leukocytes to leave lymphoid tissues and enter the blood to go to vessels in the damaged area
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During the cellular phase of acute inflammation, what causes margination and adhesion of leukocytes to the endothelium in vessels of damages area?
Activated complement proteins
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What happens to endothelial cells after leukocytes adhere to the endothelium?
- Endothelial cells separate from one another and vessels become more permeable
- Leukocytes transmigrate through the blood vessels into interstitial spaces--causes swelling
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During acute inflammation, _____ (monocytes/neutrophils) are attracted early on and (monocytes/neutrophils) are attracted later on.
- Neutrophils--early on
- Monocytes/macrophages-later on in stage
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What are the 4 steps of the cellular stage in acute inflammation?
- 1. margination and adhesion of leukocytes
- 2. transmigration
- 3. Chemotaxis
- 4. Phagocytosis
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Chemical mediators of inflammation: Plasma vs cell derived
- Plasma: made in the liver, circulate in plasma, has three distinct groups
- Cell: available in most cells, some found in granules inside cell (histamine), sometimes created by cell when stimulated
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Distinct groups of plasma derived chemical mediators:
- 1. Acute phase proteins: bradykinin
- 2. Coagulation factors: fibrinogen and prothrombin
- 3. Complement proteins
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Bradykinin is produced in the ____ and causes:
- liver
- causes pain and increased vessel permeability
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Fibrinogen is created in the ___ and causes:
liver; causes coagulation and Rouleaux (stacks of red blood cells)
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Complement proteins formed in the liver cause:
chemotaxis or leukocytes and an enhanced release of histamine from mast cells
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Histamine is found in ____ and causes:
mast cells and basophils; causes vasodilation and increased vessel permeability
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Serotonin comes from ___ and causes:
platelets; causes vasodilation and increased vessel perm.
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Thromboxane is a protaglandin that causes:
- Vasoconstriction
- bronchoconstriction
- causes platelets to clot
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Prostoglandins PGI2, and PGF2 alpha cause:
- vasodilation/increased vessel perm
- broncoconstriction
- fever
- pain
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Of the prostaglandins covered, all cause _____ but only ____ causes vasoconstriction.
- all cause bronchoconstriction
- only Thromboxane causes vasoconstriction
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Leukotrienes is a chemical mediator that causes:
- increased vessel perm.
- Bronchoconstriction
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Nitric oxide, of the inflammatory chemical mediators causes:
- vasodilation
- activation of phagocytes and metabolic burst
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What does pyogenic mean?
"pus forming"
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Name some types of Exudate caused by acute inflammation:
- Serous: low protein, water fluid in tissues
- Hemorrhagic: damaged blood vessels allow blood to leak into fluid in tissues
- Fibrinous: fibrinogen forms thick and sticky meshwork within fluid in tissues
- Suppurative (purulent): pus from phagocytes engulfing and killing pathogen and or body cells
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Inflammation at the epithelial surface can lead to ______.
Ulceration
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What are the possible outcomes of acute inflammation?
- 1. Resolution
- 2. Fibrosis and scarring
- 3. Abscess formation
- 4. Progression to chronic inflammation
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Chronic inflammation results in:
- 1. Abnormal proliferation of blood vessels (angiogenisis)
- 2. necrosis
- 3. fibrosis
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Chronic inflammation is characterized by proliferation of ____, and infiltration of ___ and ____ into the inflamed area.
- proliferation of fibroblasts
- infiltration of macrophages and lymphocytes
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Name some causes of chronic inflammation:
- Recurrent acute inflammation
- Foreign bodies
- Fungal infection
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Examples of foreign bodies that cause chronic inflammation:
fibers in lung, suture, bone fragments not connected to blood vessel after crushing injury, shrapnel fragments
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Name a fungus that can cause chronic inflammation
Coccidioides immitis causes Valley Fever
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____ is a bacterium that causes TB and often shows chronic inflammation in lung and other body parts.
Mycobacterium sp.
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________ ________ is a protistan that causes one form of severe diarrhea and often causes chronic inflammation of the lining of the intestine.
Entamoeba histoltica
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________ can cause chronic inflammation of the liver
Hep. C
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Granuloma:
- a distinct lesion seen with chronic inflammation
- clusters of epithelioid cells: macrophages the resemble epithelial cells surrounded by lymphocytes
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________ inflammation is commonly seen with foreign body, fungal infections, and TB
Granulomatous
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What leads to "acute-phase response" in inflammation?
when inflammation doesn't remain localized or if chemical mediators leave injured area and enter circulation
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What are the signs and symptoms of "acute-phase response"?
- Increase in plasma proteins (bradykinin, c-reactive protein, Serum Amyloid A protein)
- Skelatal muscle breakdown (catabolism)
- Negative nitrogen balance
- Elevated erythrocyte sedimentation rate
- Alterations in WBC count
- Fever
- Increased heart rate
- Anorexia
- Somnolence (sleepy)
- Malaise
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Systemic inflammatory response syndrome occurs when certian bacterial infections cause too much of the cytokines names _____ Factor alpha and _______ to be made.
Tumor-necrosis and Interleukin-1
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During systemic inflammatory response syndrome, vasodilation of vessels throughout the body occur. This causes what to happen?
- Causes increased perm of body vessels
- Intravascular fluid is lost--->hypotension, circulatory shock from ischemia
- Myocardial depression
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Another effect of systemic inflammation is Disseminated Inravasular Coagulation (DIC):
formation of small clots throughout blood which cause ischemia and organ damage
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What is another word for pyrexia?
- Fever!
- Temps above: 97-99.5 deg.F or 36-37.5 deg.C
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Neurons located in the _______ center of the _____ determine the "set-point" for body temp.
thermoregulatory center; hypothalmus
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Mechanism of Heat Production
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The thyroid hormones: __ and __ increase metabolic rate and increase body temp.
T3 and T4
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Increased _______ Nervous System activity causes vasoconstriction of skin blood vessels (AV shunts) and moves blood to core
Sympathetic Nervous System (SNS)
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(More/Less) SNS activity causes vasodilation of skin blood vessels (AV shunts open).
Less SNS activity
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Cause of fever is often _____ and their effect on the _________.
Cytokines cause fever and effect the Hypothamlus
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Cytokines that cause the hypothamlic thermoregulatory neurons to reset include:
- Tumor-Necrosis Factor alpha (TNF-alpha)
- Interleukin-one (IL-1)
- Protaglandins (PGI2, PGI2 alpha)
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_____ are chemicals that cause fever by causing hypothalamic them. reurons to reset set-point to a higher value.
Pyrogens
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Endogenous pyrogens are made by ?
Body cells such as Macrophages in TNF aplha and IL-1
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Fevers higher than ____ deg. F or ____ deg. C are usually due to ?
- Higher than 105 deg. F or 45 deg. C
- caused by convulsions, hyper-metabolic states, damage to the brain, excessive thyroid hormone
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Neurologic fever:
- fever due to brain damage
- resistant to antipyretic therapy and NOT associated w/ sweating
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What is the purpose of fever?
- Fever facilitates immune response
- increased interferon production
- immune cells move faster
- phagocytes eat more
- enzyme reactions occur faster--more products
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How might fever affect bacterial and viral infections?
- Bacterial: may adversely affect growth and reproduction
- Viral: causes lysomal destruction of infected body cells, limiting viral replication and spread of virus
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Four stages of Fever
- 1. Prodomal body temp. rise
- 2. Chill, shivering and chattering teeth
- 3. Cutaneous flush
- 4. Sweating (defervescence)
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Fever Stage 1: Prodomal during which body temperature rises:
headache, fatigue, malaise, nonspecific aches and vague pain
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Fever stage 2: Chills, shivering and chattering teeth
- AV shunts close to vasoconstriction of skin blood vessels and blood moves to core
- piloerection
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Fever stage 3: Cutaneous flush
Close AV shunts, vasodilation of skin blood vessels as blood moves to core
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Fever stage 4: Sweating
due to increase in body temp. begin to sweat for evaporative cooling
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What are some other common symptoms associated with fever?
- Headache
- Confusion, incoordination, agitation, delirium
- anorexia
- Mylagia
- Fatigue
- Increased respiration
- Dehydration
- Breakdown of fat stores and skeletal muscle proteins
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Fever over ____ require emergency care
106 deg.F
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How do high fevers damage the body?
- Damage neurons, impairs neurological functions
- increases metabolism-->more cardiac workload
- Can damage fetus in pregnancy
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How is fever managed?
- Correct underlying cause w/ diagnosis
- 1. sponge baths, cooling blankets, remove clothes/blankets
- 2. adequate oral and IV fluids
- 3. Antipyretic drugs such as aspirin or acetaminophen
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What does FUO stand for?
- Fever of Unknown Origin
- Malignancies, hard to diagnose infections, some drug reactions
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Histamine, serotonin, cytokines, bradykinin, arachidonic acid, and platelet-activating factor are examples of __________ mediators.
chemical
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_________ refers to heat transfer through the circulation of air currents.
Convection
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