Chapter 3- Pathology
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. What would you like to do?
- reaction of vascularized tissue to cell injury of cell death
- consider to be adaptive
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
What happens if excessive or chronic inflammation occurs? Give an example.
- Can cause even more cell injury and cell death
- Seen in bronchial asthma
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
Chronic inflammation lasts anywhere from days to years. Commonly results in:
- abnormal proliferation of blood vessels, necrosis, and fibrosis
- damages cell
Cells of inflammation: Tissue cells
- Fibroblats: connective tissue makes finers- collogen and elastin
- Mast cells: Histamine release for allergy or inflammation
Cells of inflammation: Endothelial cells-
Cells of inflammation: Leukocytes
Granulcytes or Aganulocytes
What are the three types of granulocytes (BEN)?
Basophils, Eosinophils, Neutrophils
What are the two types of Agranulocytes?
- Lymphocytes and mature plasma cells
Neutrophils are the phagocytes of _____ inflammation and Monocytes are the phagocytes of _____ inflammation.
proteins that are toxic to parasitic worms
histamine released in allergy response or inflammation
cell-mediated and anti-body mediated immunity
What are inflammatory mediators? Name two types.
- A variety of chemicals in plasma that are released from cells with specific effects
- Cytokine and Chemokine
chemical mediator secreted by one cell that has specific effects on a different cell
- chemical mediators secreted by one cell that attracts a different cell type to a specific area
What is exudation?
- Occurs during inflammation process
- The movement of fluid, leukocytes, and proteins from the blood into the damaged area
What can trigger acute inflammation?
Anything that damages or kills cells
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
Acute inflammation has two distinct, overlapping phases:
Vascular and cellular
Vascular phase of Acute inflammation:
exudation of fluid and plasma proteins, from blood vessels into tissue
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
During vascular phase of inflammation, what causes vasoconstriction, followed by vasodilation?
- Nitric oxide
- some other chemical mediators
During the vascular phase of inflammation, what aids in increased vascular permeability after vasoconstriction/vasodilation?
- activated complement proteins
Cellular phase of acute inflammation:
release of chemical mediators, triggering specific actions by specific cells
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
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
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
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
What are the 4 steps of the cellular stage in acute inflammation?
- 1. margination and adhesion of leukocytes
- 2. transmigration
- 3. Chemotaxis
- 4. Phagocytosis
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
Distinct groups of plasma derived chemical mediators:
- 1. Acute phase proteins: bradykinin
- 2. Coagulation factors: fibrinogen and prothrombin
- 3. Complement proteins
Bradykinin is produced in the ____ and causes:
- causes pain and increased vessel permeability
Fibrinogen is created in the ___ and causes:
liver; causes coagulation and Rouleaux (stacks of red blood cells)
Complement proteins formed in the liver cause:
chemotaxis or leukocytes and an enhanced release of histamine from mast cells
Histamine is found in ____ and causes:
mast cells and basophils; causes vasodilation and increased vessel permeability
Serotonin comes from ___ and causes:
platelets; causes vasodilation and increased vessel perm.
Thromboxane is a protaglandin that causes:
- causes platelets to clot
Prostoglandins PGI2, and PGF2 alpha cause:
- vasodilation/increased vessel perm
Of the prostaglandins covered, all cause _____ but only ____ causes vasoconstriction.
- all cause bronchoconstriction
- only Thromboxane causes vasoconstriction
Leukotrienes is a chemical mediator that causes:
- increased vessel perm.
Nitric oxide, of the inflammatory chemical mediators causes:
- activation of phagocytes and metabolic burst
What does pyogenic mean?
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
Inflammation at the epithelial surface can lead to ______.
What are the possible outcomes of acute inflammation?
- 1. Resolution
- 2. Fibrosis and scarring
- 3. Abscess formation
- 4. Progression to chronic inflammation
Chronic inflammation results in:
- 1. Abnormal proliferation of blood vessels (angiogenisis)
- 2. necrosis
- 3. fibrosis
Chronic inflammation is characterized by proliferation of ____, and infiltration of ___ and ____ into the inflamed area.
- proliferation of fibroblasts
- infiltration of macrophages and lymphocytes
Name some causes of chronic inflammation:
- Recurrent acute inflammation
- Foreign bodies
- Fungal infection
Examples of foreign bodies that cause chronic inflammation:
fibers in lung, suture, bone fragments not connected to blood vessel after crushing injury, shrapnel fragments
Name a fungus that can cause chronic inflammation
Coccidioides immitis causes Valley Fever
____ is a bacterium that causes TB and often shows chronic inflammation in lung and other body parts.
________ ________ is a protistan that causes one form of severe diarrhea and often causes chronic inflammation of the lining of the intestine.
________ can cause chronic inflammation of the liver
- a distinct lesion seen with chronic inflammation
- clusters of epithelioid cells: macrophages the resemble epithelial cells surrounded by lymphocytes
________ inflammation is commonly seen with foreign body, fungal infections, and TB
What leads to "acute-phase response" in inflammation?
when inflammation doesn't remain localized or if chemical mediators leave injured area and enter circulation
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
- Increased heart rate
- Somnolence (sleepy)
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
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
Another effect of systemic inflammation is Disseminated Inravasular Coagulation (DIC):
formation of small clots throughout blood which cause ischemia and organ damage
What is another word for pyrexia?
- Temps above: 97-99.5 deg.F or 36-37.5 deg.C
Neurons located in the _______ center of the _____ determine the "set-point" for body temp.
thermoregulatory center; hypothalmus
Mechanism of Heat Production
The thyroid hormones: __ and __ increase metabolic rate and increase body temp.
T3 and T4
Increased _______ Nervous System activity causes vasoconstriction of skin blood vessels (AV shunts) and moves blood to core
Sympathetic Nervous System (SNS)
(More/Less) SNS activity causes vasodilation of skin blood vessels (AV shunts open).
Less SNS activity
Cause of fever is often _____ and their effect on the _________.
Cytokines cause fever and effect the Hypothamlus
Cytokines that cause the hypothamlic thermoregulatory neurons to reset include:
- Tumor-Necrosis Factor alpha (TNF-alpha)
- Interleukin-one (IL-1)
- Protaglandins (PGI2, PGI2 alpha)
_____ are chemicals that cause fever by causing hypothalamic them. reurons to reset set-point to a higher value.
Endogenous pyrogens are made by ?
Body cells such as Macrophages in TNF aplha and IL-1
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
- fever due to brain damage
- resistant to antipyretic therapy and NOT associated w/ sweating
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
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
Four stages of Fever
- 1. Prodomal body temp. rise
- 2. Chill, shivering and chattering teeth
- 3. Cutaneous flush
- 4. Sweating (defervescence)
Fever Stage 1: Prodomal during which body temperature rises:
headache, fatigue, malaise, nonspecific aches and vague pain
Fever stage 2: Chills, shivering and chattering teeth
- AV shunts close to vasoconstriction of skin blood vessels and blood moves to core
Fever stage 3: Cutaneous flush
Close AV shunts, vasodilation of skin blood vessels as blood moves to core
Fever stage 4: Sweating
due to increase in body temp. begin to sweat for evaporative cooling
What are some other common symptoms associated with fever?
- Confusion, incoordination, agitation, delirium
- Increased respiration
- Breakdown of fat stores and skeletal muscle proteins
Fever over ____ require emergency care
How do high fevers damage the body?
- Damage neurons, impairs neurological functions
- increases metabolism-->more cardiac workload
- Can damage fetus in pregnancy
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
What does FUO stand for?
- Fever of Unknown Origin
- Malignancies, hard to diagnose infections, some drug reactions
Histamine, serotonin, cytokines, bradykinin, arachidonic acid, and platelet-activating factor are examples of __________ mediators.
_________ refers to heat transfer through the circulation of air currents.
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