Inflammation and would healing

Inflammation

Inflammation

normal, non-specific defense that ocurs due to a breach in the first line of defense.

1. injury

2. infectious agent

3. antibody activity

Common inflammation-initiating events: [3]

1. prostaglandins

   1. and leukotrienes

2. serotonin (5-HT)

3. Histamine (H1)

4. Complement (C’)

Chemical mediators: [5]

They are synthesized from damaged cell membranes

Where do prostaglandins come from?

released from mast cells and basophils (degranulation)

Where does histamine come from?

1. lines mucous membranes

2. lines capillaries

3. in loose connective tissue near blood vessels

Where are mast cells found? [3]

Released from activated platelets

Where does serotonin come from?

When collagen is exposed by damage to blood vessel walls

When are platelets activated?

Pokes holes in the cell membrane, allows water and ions to enter the cell.

Actions of complement:

1. some bacterial CW endotoxins

2. Ag-Ab complexes (IgA, IgG, IgM, but not
   IgE)

Complement fragments in circulation get activated by: [2]

prostaglandin. Histamine usually only starts the process.

Which is more likely important: pGs or H1?

1. predicts signs and symptoms

2. predicts drugs

Why is it important to know the chemical mediator? [2]

1. vasodilation

2. increased vascular permeability

3. chemotaxis

4. stimulation of smooth muscle contraction

5. stimulation of goblet cells to produce mucous

6. stimulation of nociceptors to produce pain.

Six effects of chemical mediators:

Vasodilation

Chemical mediators act on vascular smooth muscle to cause it to relax, resulting in:

results in more blood flow in area so more oxygen, nutrients, WBC,, waste removal

Benefit of vasodilation:

1. heat and

2. redness

S+S of vasodilation: [2]

Causes transient vasoconstriction first

5-HT causes what kind of vasodilation?

Vascular permeability

Chemical mediators cause capillary wall endothelial cells to retract, leaving caps that cells and fluid pass through

Allows WBCs, plasma proteins, and nutrients to get to site

benefits of vacular permeability:

tissue swelling

S+S of increased vascular permeability

Chemotaxis

Promotes migration of WBCs to affected area, find WBC in local exudate

1. on bronchi (bronchoconstriction)

2. on GI tract (increased peristalsis)

Examples of smooth muscle contraction :

Wheezing

S+S of smooth muscle contraction

Diarrhea

S+S of GI tract muscle contraction

prevents further inhalation of injurious stimuli

Benefit of bronchoconstriction

promotes elimination of injurious stimuli

benefit of GI smooth muscle contraction

1. respiratory

2. digestive

3. urinary

4. reproductive tract

Areas with goblet cells: [4]

Goblet cells

cells that produce mucous

traps injurious stimuli

Benefit of mucous production

Warns of injury

benefit of stimulation of nociceptors:

prostaglandins and histamine

Which chemical mediators do all 6 effects:

only intravascular effects:

1. vasodilaion

2. increased vascular permeability

3. smooth muscle contraction

4. chemotaxis

Serotonin only does which effects? [4]

1. vasocilation

2. increased vascular permeability

3. chemotaxis

4. degranulates mast cell basophils to release H1

Complement only does which effects: [4]

Neutrophils (PMNs) arrive within 6-12 hours but short lived (1-2 days)

Which WBC arrives to the site first?

Monocytes

Develops into macrophages when they get in tissues and arrive after the neutrophils

Neutrophils

WBC that circulates in the blood until recruited into tissue by chemotaxis

Ingests foreign matter and bacteria (phagocytose)

How do neutrophils work to kill infection?

1. produces pyrogens

2. chemotactic factors for macrophages

Neotrophils produce what?

Later than neutrophils (3-7 days) in response to a variety of chemotactic factors

When do macrophages arrive?

1. phagocytose and destroy bacteria/old cells

2. release cytokines (chemical messengers)

What do macrophages do?

only if infection

Pus is present when?

1. fever

2. increased WBC count

3. increased ESR

4. increased CRP

Systemic infection S+S [4]

Pus

exudate is a mixture of dead cells and bacteria, may also find white blood cells

1. heat

2. redness

3. swelling

4. WBC in exudate

Local S+S of infection: [4]

WBCs release cytokines (e.g., IL-1) which are
pyrogens and stimulate pG synthesis at thermostat
(hypothalamus) to reset it (higher)

Body produces heat to match new setting so temp. is
elevated

Fever etiology:

body temp normally at 37ºC, fever occurs (due to
pG synthesis at hypothalamus) and sets temperature point to
39ºC

Stimulus for fever:

increased metabolism,

kills or alters
replication of microorganisms

benefits of a fever: [2]

altered cellular protein structure,
dehydration,

increased O2 demand,

increased metabolic demand

fever risks: [3]

Only when underlying cause is also being treated.

when to treat fever?

ASA and acetaminophen block pG
synthesis at thermostat- reset to (N

Meds to treat fever:

Due to inflammation

Why do most patients 24h after surgery have a slight fever?

Inflammation releases plasma proteins like fibrinogen, etc..

Fibrinogen causes RBCs to become stickier and cross-link, making them heavier, so they sediment faster.

Why can infection increase erythrocyte sedimentation rate?

C-reactive protein

non-specific, produced by liver in acute inflammation. Indicates presence, not cause, of inflammation. More sensitive than ESR

role only when initiating event is mediated by H1

when are anti-histamines used to treat inflammatino?

Blocks Lt and pGs (anti-inflammatory)

Steroids to treat inflammation (MOA)

Block Cycloxygenase (COX) so no pGs synthesis. Lts still cause inflammation so not very “anti-inflammatory” except at high dose

Acetaminophen and Non-steroidal anti-inflammatory drugs (NSAIDs) for treating infection MOA

Vasoconstriction to decrease blood flow. SLows inflammation but better by numbing nociceptors

How can cold treat inflammation?

vasodilation so promotes blood flow and removal of waste. Can cause more redness, swelling, pain.

HOw can heat treat inflammation?

Repair (scar tissue formation)

the end process of inflammation

1. WBC phagocytose debris

2. fibrin mesh of clo formed

3. fibroblasts recruited

Repair phase 1:

-Fibrin clot replaced by scar tissue
– Fibroblasts proliferate
– Fibroblasts secrete collagen
– Collagen is laid down
– Epithelial cells proliferate
– Angiogenesis
– Granulation tissue grows in
– Wound contraction occurs

Repair phase 2:

remodeling and maturation

– Normally complete within 2 years
– Continued cellular differentiation, scar formation and scar remodeling
– Scar becomes avascular as capillaries disappear

Repair phase 3:

Healing by primary intention

would closees side to side, is rapid. Minimal tissue loss.

Healing by secondary intention

Closure ad repair from the bottom up and the sides fill in. Slower healing process, lots of tissue loss. Moist environment is needed.

1. lack of oxygen and nutrients and white blood cells

2. local infection or dirt or material

Interferences that can cause poor wound healing [2]

1. low BP (hypovolemia)

2. excess fat tissue

3. pain

4. smoking

Poor wound healing risk factors to do with poor effusion, low oxygen: [4]

1. accumulated blood or other material

2. bacteria/infection

Poor wound healing risk factors to do with competing for wbc action [2]

1. poorly controlled diabetes

2. metabolic syndrome

Poor wound healing risk factors to do with competing for excess glucose [2]

Steroids (hydrocortisone)

intererence with WBC/cytokines tha can cause poor wound healing

Tissue dehydration

Cells can’t move easily to join, can cause poor wound healing

Diet lacking in calories, protein, vitamin C, calcium, and other nutrients

Lack of required building blocks that can be a cause for poor wound healing

Acute inflammation

inflammatino lasting less than 2 weeks

chronic inflammation

inflammation lasting longer than 2 weeks

presence of infection or barrier to repair (foreign object like a splinter, dirt)

Chronic inflammation is caused by:

1. more WBCs

2. repair not achieved

Chronic inflammatino results in: [2]