Lecture 3: Inflammation & Healing Flashcards
(39 cards)
Inflammation
A nonspecific, predictable response to injury, occurring only in living tissues. The purpose of inflammation is to start the healing process. This includes a series of interconnected events that involves a coordinated reaction by cells, tissues, organs or the entire body.
It involves vessels, blood cells, nerves and chemicals.
It is a dynamic process that can last minutes, days, months or years.
It causes redness, swelling, warmth and pain.
Sudden onset and short duration is called acute inflammation.
Slower onset lasting longer is called chronic inflammation.
Function of the inflammatory reaction:
- to inactivate the injurious agent
- to break down & remove dead cells
- to initiate the healing of tissues
Inflammation has an overall protective role and is usually beneficial to the body, however it may have some side effects if left unchecked.
Five cardinal signs and symptoms of inflammation:
- Heat: caused by vasodilation and increased blood flow
- Erythema (redness): caused by vasodilation and increased blood flow
- Edema (swelling): by fluid and cells leaking into the interstitial space
- Pain or tenderness: caused by direct trauma: bradykinins, histamines, swelling of nerves
- Loss of use / dysfunction: caused by joint, ligament, muscle and tendon damage
- Other systemic symptoms:
body ache, fatigue, weakness, decreased appetite
Inflammation Pathogenesis
Inflammation is a process that involves the following key components:
I. . Circulatory changes: the first response to injury, involves increased blood flow through inflamed tissues, causing redness, swelling and warmth of the skin.
II. Vessel Wall changes: damage to the endothelial lining, the vessel walls and to close-by tissues like arterioles, capillaries and venules cause the vessel walls to become leakier which causes increased permeability.
III. Immune Response: a release of inflammatory mediators or chemicals like histamine, bradykinin, arachidonic acid and also activation of the complement system
IV. Cellular response: fluid imbalance, emigration of leukocytes, phagocytosis
Inflammation:
I. Circulatory changes:
the first response to injury, involves increased blood flow through inflamed tissues, causing redness, swelling and warmth of the skin.
Arterioles vasoconstrict for a few seconds first and then vasodilate, this causes blood to rush into the capillary network (this is called hyperemia) and causes redness, swelling and warmth of the skin.
Inflammation:
II. Vessel Wall changes:
damage to the endothelial lining, the vessel walls and to close-by tissues like arterioles, capillaries and venules causes the vessel walls to become leakier which is called increased permeability. These four processes cause this increase:
- increased hydrostatic blood pressure
- slowing down of the circulation
- adhesion of leukocytes and platelets to the inner lining of the the vessel wall
- release of mediators (chemicals) from leukocytes, platelets and endothelial cells
- all increase the vessel wall or capillary endothelium leakiness
Inflammation:
III. Immune Response:
a release of inflammatory mediators or chemicals in response to injury some from the plasma and some from the cells themselves:
- Biogenic Amines:
a. Histamine
b. Bradykinin
- Complement system
- Arachidonic acid Derivatives
- Cytokines
Inflammation:
III. Immune Response:
- Biogenic Amines:
a. Histamine: released from platelets and mast cells, occurs quickly and only lasts less than 30 minutes (deactivated quickly by the enzyme histaminase) provokes contraction of the endothelial cells of blood vessel walls and makes gaps in the endothelial lining, these gaps allow larger substances to flow through and makes them more leaky.
b. Bradykinin: released from plasma, similar to histamine but slower reaction and also accounts for the pain felt in inflammation
Inflammation:
III. Immune Response:
- Complement system:
Complement system:
several proteins that are activated in a cascade and act on one another (numbered from C1 - C9). They are activated in three ways:
- Classical pathway: activated by antibodies binding to antigens
- Alternative pathway: activated by bacteria endotoxins (fungi, snake venom etc.) that are carbohydrates on the surface of bacteria
- Lectin pathway: activated by macrophages that digest bacteria that release chemicals that cause the liver to produce lectins
All three pathways lead to the formation of the membrane attack complex (MAC). This complex kills cells by boring a hole in their membrane.
The complement system also causes a histamine release which causes vasodilation and promotes chemotaxis
All three pathways lead to the formation of the membrane attack complex (MAC). This complex kills cells by boring a hole in their membrane.
Inflammation:
III. Immune Response:
- Arachidonic acid Derivatives:
- Arachidonic acid Derivatives: derived from the phospholipids of cell membranes
Activates lipoxygenases that form leukotrienes (these promote chemotaxis and increased permeability)
Activates cyclooxygenases that form prostaglandins (these cause vasodilation and increased permeability, mediate pain and fever)
Prostacyclin: counteracts the effects of thromboxane
Thromboxane: promotes platelet aggregation, thrombosis and vasoconstriction
Inflammation:
III. Immune Response:
- Cytokines:
Cytokines: produced by leukocytes, two important ones:
A. interleukin-1 (promotes inflammatory reaction)
B. tumor necrosis factor (TNF)q
Inflammation:
IV. Cellular responses:
because of the increased permeability of vessel walls, leakage of fluid occurs from the capillaries into the interstitial space. This fluid is called transudate and it is the swelling or edema that occurs with inflammation. It is full of proteins but has very few blood cells (red or white, platelets). As this process continues more proteins, circulating platelets and white blood cells emigrate or move through the leaky vessel walls into the interstitial space and this fluid is now called exudate.
- Emigration of leukocytes:
Increased permeability of the vessel wall that is caused by chemicals is called chemotaxis
Leakage of fluid into the interstitial spaces forming edema and exudate.
Chemotaxis: movement of WBC’s in response to chemicals, they move up their concentration gradient
- Phagocytosis:
When the PMN’s (polymorphonuclear) reach the source of the inflammation, the bacteria, they stop moving and become stationary scavengers. They engulf and digest the bacteria.
This process occurs in four stages:
- PMN’s recognize the bacteria as foreign
- Pseudopods extend from the PMN’s plasma membrane and surround the bacteria
- Engulfment of the bacteria into the PMN and fusing with a lysosome
- Lysosomes full of bactericidal substances digest the bacteria (called degranulation)
Edema:
Transudate:
Exudate:
Edema: body tissues contain excessive fluids
Transudate: this extravascular fluid passing through a membrane has a low concentration of cells and low protein content, this fluid causes edema.
Exudate: this extravascular fluid passing through a membrane that has been altered from inflammation has a high concentration of cells and proteins.
Cells of Inflammationq
- Neutrophils (polymorphonuclear cells (PMN’s))
- Eosinophils
- Basophils
- Macrophages
- Platelets
- Other cells
Cells of Inflammation:
Neutrophils: (polymorphonuclear) PMN’s (60-70% of all WBCs)
First to arrive (in acute inflammation)
Most numerous
Highly mobile
Capable of phagocytosis (engulfing cells)
Contain bactericidal lysosomes
Produce cytokines that produce chemical mediators that promote inflammation, recruit new leukocytes and cause systemic symptoms.
Cells of Inflammation:
Eosinophils: (2-3% of all WBC’s)
Appear 2-3 days after the start of inflammation (slower to arrive)
Mobile but slower than neutrophils
Phagocytes
Bactericidal
Prominent in allergic reactions
Prominent in parasitic reactions
Stick around longer so occur in chronic inflammation
Cells of Inflammation:
Basophils: (less than 1% of WBC’s)
Most prominent in inflammatory reactions and allergic reactions mediated by immunoglobulin IgE
Filled with histamine
Precursors to mast cells
Cells of Inflammation:
Macrophages:
Derived from monocytes
Appear 3-4 days after onset of inflammation
Long lived cells (typical in chronic inflammation)
Live in tissues not blood stream
Phagocytosis
Secrete cytokines that produce inflammatory mediators
Cells of Inflammation:
Platelets (thrombocytes):
fragments of a megakaryocyte
Early to arrive with PMN’s (polymorphonuclear)
Contain many granular substances (histamine, coagulation proteins, cytokines, growth factors)
Release these substances in response to contact to the endothelial lining or the extracellular matrix
Causes coagulation
Cells of Inflammation:
components of chronic inflammation
Lymphocytes - occur in chronic inflammation
Plasma Cells (a modified lymphocyte)
Healing & Repair:
Types of Inflammation Classified by duration:
Types of Inflammation Classified by duration:
- Acute Inflammation: sudden onset, last for a few hours to a few days, causing swelling, redness, pain, heat, and or loss of function.
Exudate: Polymorphonuclear neutrophils (PMN’s) arrive first, then monocytes, eosinophils and sometimes basophils. PMN’s last 2-4 days then die and are replaced by macrophages that are formed from monocytes
- Chronic Inflammation: lasts longer, weeks to months to years, onset is delayed, may not have signs of inflammation. Usually an extension of acute inflammation or prolonged healing of acute inflammation or it may be caused by persistence of the causative agent that started the acute inflammation. There is more extensive tissue damage and may cause fibrosis (hardening of tissue).
Exudate: lymphocytes, macrophages and plasma cells
Causes of Inflammation
Causes of Inflammation
Infections: living pathogens infect (bacteria, virus, protozoa, fungus or helminth worms)
Chemical causes: organic or inorganic, industrial or medicinal, exogenous or endogenous
Physical causes: heat, irradiation and trauma to tissue
Foreign bodies: a thorn or a bee sting
Immune causes: hypersensitivity reactions
Types of Inflammation
- Serous
- Fibrinous
- Purulent
- Ulcerative
- Pseudomembranous
- Granulomatous
Types of Inflammation
- Serous
Mildest form of inflammation, usually self limiting
Exudate is a clear fluid made of the non-cellular portion of blood
called serum rich in proteins
Occurs in the early stages of inflammation
Typical in viral infections (eg/ Herpes Virus)
