Inflammation Flashcards
Inflammation?
Local response of vascular tissue or injury
Vascular tissue?
vessels and their cells (the fluid inside)
What is inflammation a part of?
Defense and healing [ defense -> prevents further injury/extension of initial injury ]
Do cells become individually inflamed?
No, but tissues can
What are the aims for inflammation?
- localize and remove agent of injury (ex. bacteria, toxin, chemical)
- removes injured cells and debris
- facilitates healing [clears out any pathogens; intact perfusion]
What is an important concept to remember about inflammation?
With inflammation ALWAYS comes some form of tissue damage (normal cells will die)
What does the prefix “angio-“ mean?
Blood vessel
Acute Inflammation?
Brief, early response (mins/hrs/day) with short duration.
What are the attributes of acute inflammation?
- granulocytes (mainly neutrophils but also eosinophils and basophils)
- triggers the immune response. There are 2 responses: vascular and cellular
Chronic Inflammation?
Longer durations (weeks to years)
What are the attributes of chronic inflammation?
- agranulocytes (lymphocytes & macrophage)
- self-maintaining (drives itself)
- Process includes: angiogenesis, fibrosis, and necrosis
Angiogenesis?
Formation of new blood vessels
Fibrosis?
Formation of fibrous tissues
Necrosis?
Death of own cells
What are the responses for acute inflammation?
Vascular and cellular responses
there are many cell types involved
Vascular response?
characterized by changes in small blood vessels @ site of injury
What occurs during vasoconstriction in the vascular response?
Stat, brief vasoconstriction to decrease blood flow and prevent further blood loss (b/c clotting takes time), but brief because you do not want to cut off the cellular response.
What occurs during vasodilation in the vascular response?
It occurs once histamine and prostaglandin are released. Plasma and inflammatory cells (granulocytes) release chemicals called mediators that affect blood vessels.
- Histamine brings capillary dilation and increases capillary permeability.
- Prostaglandin (local hormones) brings capillary dilation, increases capillary permeability and mediates pain.
- increase in blood flow (warmth & erythema)
What are some of the functions of histamine in the vascular response?
- brings capillary dilation (vasodilation)
- increases capillary permeability
What are some of the functions of prostaglandin in the vascular response?
- brings capillary dilation (vasodilation)
- increases capillary permeability
- sensation of pain
Hyperemia?
An excess of blood in the vessels
Prostaglandin?
Local hormones (local because it is secreted in different parts of the body so they have many functions based on where they are secreted)
What occurs during the increase in capillary permeability in the vascular response?
There is an increase in capillary permeability because exudate forms and enters extravascular spaces causing swelling, pain and loss of function.
Fluid shift?
Exudate from vessels to tissue (interstitial space)
What occurs during the fluid shift in the vascular response?
Exudate goes from vessels to tissue (interstitial space) therefore there is a loss of proteins which decreases the capillary osmotic pressure and increases the interstitial osmotic pressure (swelling)
What occurs in vascular response?
Injury -> stat vasoconstriction (its brief to minimize blood loss & facilitate healing) -> inflammatory mediators are activated (histamine & prostaglandin) -> vasodilation -> hyperemia -> erythema & warm -> increases permeability -> exudate formation -> fluid shift -> swelling -> pain (resulting in immobilization d/t pain)
Erythema?
Redness
Why does warmth occur in the inflammatory process?
B/c of increased blood flow (which means increased heat)
What is exudate composed of?
1) Fluid
2) Cells
3) Protein
What usually occurs in the vascular response due to pain?
Immobilization
What are the 3 main steps in the vascular response?
1) vasoconstriction
2) vasodilation
3) Increased permeability
Moving an injured wrist is going to hurt. What would you do to facilitate healing?
Immobilize the injured wrist
Cellular response?
delivery of leukocytes to the site of injury via blood vessels
What is a 1. local and 2. systemic
manifestation?
- @ site of injury
2. elsewhere in the body
What are the 4 Cardinal signs of inflammation?
- Erythema
- Swelling
- Warmth
- Pain
Why does erythema occur?
d/t hyperemia (increase in blood flow) to site
Why does swelling occur?
because exudate forms
Why does warmth occur?
Blood carries heat
Why does pain occur?
Exudate causes swelling which causes pain due to stretched tissue at site
What is the 5th cardinal sign?
Loss of function (may not always be obvious)
Exudate?
Composed of fluid+cells+protein (antibodies, complement etc)
What kind of manifestations are exudates?
They are all local but in severe cases you will have systemic manifestation
Cellular response?
It is initiated by the delivery of leukocytes to the site of injury via blood vessels.
What are the 3 main steps in a cellular response?
A) Adhesion and margination on the endothelium
B) Diapedesis
C) Chemotaxis
What happens during the process of adhesion and margination on the endothelium (in cellular response)?
Leukocytes exit central blood stream. There is a pavementing of leukocytes which stick to the epithelium on the blood vessel wall which initiated the rouleau formation of erythrocytes which is facilitated by a decreased blood flow and complementary adhesion molecules (eg. selectins, integrins)
Rouleau formation?
Erythrocytes stacking
Why does the rouleau formation occur in the adhesion and margination process of a cellular response?
Erythrocytes stack to decrease blood flow which is caused by the increased resistance.
Name some examples of adhesion molecules.
Selectins, integrins
In a nutshell, what is diapedesis?
Leukocytes escape out of BV in CT
What are 2 other names for diapedesis?
- Emigration
- Transmigration
Are platelets cells?
NO (they are fragments of cells)
What happens during the process of diapedesis in the cellular response?
Leukocytes pass through the intact walls of the capillaries. They go from a vascular space into extravascular tissue through the endothelium and the cells enter the interstitial fluid (they bring along some cells ex. WBC’s, fluids, proteins such as complement and Ab)
What happens during the process of chemotaxis in the cellular response?
Leukocytes migrate towards the site of injury along a chemical gradient/trail.
What happens in the cellular response once the leukocytes are at the site of injury?
Antibodies opsonize microbes for neutrophil recognition. Then the receptor activation triggers phagocytosis by neutrophils which results in phagocytosis of cell debris & foreign particles.
*BIO 152/153 REVIEW *
What is opsonization?
Antibodies coat foreign cells which allows for macrophage attachment causing phagocytosis to occur.
In detail, explain the vascular response.
The vascular response is characterized by changes in small blood vessels @ the site of injury. The first process to occur is stat, brief vasoconstriction to decrease blood flow and prevent further blood loss (b/c clothing takes time), but brief because you don’t want to cut off the cellular response. Next, vasodilation occurs once histamine and prostaglandin are released. Plasma and inflammatory cells (granulocytes) release chemicals called mediators that affect blood vessels and nerves. Histamine and prostaglandin both bring capillary dilation (vasodilation) and increase capillary permeability. However, prostaglandins also mediates pain. This results in hyperemia (increased blood flow) which brings on warmth and erythema. Lastly, there is an increase in capillary permeability because exudate forms and enters extravascular spaces resulting in swelling, pain and loss of function. There is fluid shift (exudate goes from the vessels to tissue [interstitial space]). This causes a loss of proteins which decreases the capillary osmotic pressure and increases the interstitial osmotic pressure resulting in swelling. [Swelling causes pain due to the stretched tissue at site and this is often results in immobilization d/t pain]
In detail, explain the cellular response?
The cellular response is initiated by the delivery of leukocytes to the site of injury via blood vessels. The first process to occur is adhesion and margination on the endothelium. In this stage, leukocytes exit the central blood stream and there is pavementing on leukocytes that stick to the epithelium on the blood vessel wall. This results in the rouleau formation of erythrocytes which is facilitated by the decrease in blood flow (due to increased resistance) and complementary adhesion molecules. Next, diapedesis occurs as the leukocytes pass through the intact walls of the capillaries. The leukocytes go from vascular space into extravascular tissue through the endothelium. The cells then enter the interstitial space (WBCS, fluids, proteins such as complement and antibodies). Chemotaxis occurs once the leukocytes are in the interstitial space. Leukocytes migrate towards the site of injury along a chemical gradient. Once the leukocytes get to the site of injury, antibodies opsonize microbes for neutrophil recognition. The receptor activation triggers phagocytosis by neutrophils which results in phagocytosis of cell debris and foreign particles.
What is a local manifestation?
@ the site of injury
What is a systemic manifestation?
Elsewhere in the body
Name all of the types of exudate.
- Serous (Serum) Exudate
- Purulent/Suppurative Exudate
- Hemorrhagic Exudate
- Fibrinous Exudate (fibrin)
- Membranous Exudate
Serum?
Liquid from centrifuged tube from previously clotted blood, so clotting factors are formed and allowed to settle.
What are the characteristics of Serous (serum) Exudate?
- More fluid than other types of exudate (still contains proteins and cells just MORE fluid)
- watery exudate
- indicates a mild injury (doesn’t require as many defence cells) and acute inflammation
Purulent?
pus
Pus?
Dead leukocytes, dead bacteria, cellular debris, proteins
What are the characteristics of Purulent/Suppurative Exudate?
- WBC, protein, necrotic debris (pus)
- foul odour from dead cells
- cloudy, white
- usually a sign of a bacterial infection
- indicates severe acute inflammation
What is another name for purulent exudate?
suppurative exudate
What are the characteristics of Hemorrhagic Exudate?
- cells, proteins, fluid & ERYTHROCYTES (RBC’s move across the capillary into the tissue)
- appears red (b/c of the presence of RBC’s)
- indicates severe injury
What are the characteristics of Fibrinous Exudate (Fibrin)?
- Cells, proteins, fluid & FIBRE (collagen)
- increase on fibrinogen which gives rise to the fibrous strands
- forms a sticky mesh (DIFF than clotting)
- less common
What are the characteristics of Membranous Exudate?
- Develops on a membrane surface
- cells, proteins, fluid AND pus, necrotic cells, fibropurulent exudate
- severe or chronic inflammation
(not very common)
What is the difference between serum and plasma?
Serum is a liquid from a centrifuged tube from previously clotted blood so clotting factors are formed & allowed to settle. Plasma differs in that it still contains clotting factors since centrifugation occurs without clotting)
Which exudate occurs as a result of a severed vessel?
Hemorrhagic exudate
What is the name of the exudate that you may see on a wound and if you do, what does that indicate?
Purulent/Suppurative Exudate. It indicates an infection and the patient needs to start an antibiotic.
Which exudate is a result of a mild injury?
Serous [serum] exudate
Which exudate occurs as a result of a severe or chronic inflammation?
Membranous exudate
Which exudate forms a sticky mesh?
Fibrinous Exudate (Fibrin)
What is considered to be the body’s “thermostat”?
- What is the set point?
Hypothalamus; set point 37 degrees
What occurs with most infections?
Fever (unless they are mild and short-lived)
What are systemic manifestations?
- not at the site of infection/injury
- non-specific (eg. general malaise, fatigue, headache, fever)
Malaise?
General feeling of not feeling well.
Fever?
Elevated body temperature above normal.
What are some of the accidental benefits of a fever?
- Increased temperature denatures proteins
- Increased temperature can kill bacteria (but if its that high, it will kill normal cells as well)
- Inhibits the growth and reproduction of pathogens (unintentional defence)
- Accelerates phagocytosis & immune response
Pyrogens?
Substance producing fever
When should you treat a fever?
When a fever is too high, uncomfortable, or is chronic
Prostaglandin E2 (PGE2)?
A local hormone that sends a signal to neurons in the pre-optic area in the hypothalamus
Name an important inflammation protein.
C-reative protein
Where are exogenous pyrogens produced? Name an example.
Produced from bacteria; ex. Lipopolysaccharide in cell well.
What occurs in the phase of exogenous pyrogens in the pathogenesis of a fever?
Proteins being to LPS and form a complex with a nearby macrophage. This causes synthesis and release of cytokines.
What occurs in the phase of endogenous pyrogens in the pathogenesis of a fever?
The endogenous pyrogens are activated by cytokines. Here, neutrophils and macrophages release interleukin-1 which stimulates arachidonic pathway forming PGE2.
Explain the pathogenesis of fever.
Exogenous pyrogens [Proteins bind to LPS and form a complex with nearby macrophage which causes synthesis and release of cytokines] -> Cytokines activate Endogenous Pyrogens [Neutrophils and macrophages release interleukin-1] -> stimulates arachidonic pathway -> forms prostaglandin E2 -> adjusts set point via cyclic AMP acting as a second messenger.
CRP?
C-reactive protein is a serum marker for inflammation.
Where is C-reactive protein produced and what kind of protein is it?
Produced in the liver in response to inflammation; hepatic protein
What does C-rp play a role in?
Plays a role in defense and healing via complement
Which condition is C-RP increases linked with?
Cardiovascular disease (more specifically, atherosclerosis)
What can increased CRP with no evidence of obvious inflammation indicate?
Vascular damage
When is treatment necessary for inflammation?
If it is too severe, painful or chronic
What are the treatment options for inflammation?
- Apply cold
- Apply pressure/compress
- Elevate
- Apply Heat
- Non-steroidal anti-inflammatory drugs
- Steroidal anti-inflammatory drugs
What does NSAID’s stand for? What is a common drug.
Non-steroidal anti-inflammatory drugs; aspirin
What does applying cold/ice do?
increases vasoconstriction, decreases blood flow, decreases exudate, decreases swelling, decreases pain
What does applying pressure/compress do?
constricts the vessel from the outside, decreases blood flow, decreases swelling, decreases pain
What does elevating do?
decreases blood flow, decreases swelling, decreases pain
What does applying heat (1-2 hrs after) do?
Vasodilation, increases blood flow, brings defence cells to area = phagocytosis
What do NSAID’s do?
Decrease prostaglandin synthesis = decreased inflm = decreased pain
What do steroidal anti-inflammatory drugs do?
decrease permeability = decrease exudate = decrease swelling;
decrease prostaglandin and histamine release (inflammatory mediators)
inhibits WBC’s and mast cell activity @ site
