Chapter 9 - Inflammation, tissue repair, and wound healing

first line of defense

non-specific, external defenses

• mechanical barriers (unbroken skin and mucous membranes)

• secretions → tears, sweat, gastric juice (these can neutralize pathogens)

second line of defense

non-specific → mechanical and internal defenses

• phagocytosis and inflammation

• interferon

these are innate defenses, and non-specific (meaning they do not distinguish between virus, bacteria, or pathogens)

third line of defense

specific defenses

• production of specific antibodies

• the activation of lymphocytes (immune cells) very specific (can distinguish pathogens)

Inflammation

protective and normal defense mechanism

• -itis

• signs and symptoms serve as warning for a problem because the problem could be hidden within the body

• it is not the same as infection, but infection is a cause of inflammation

chronic inflammation can disrupt insulin

Causes of inflammation

1. direct physical damage → cuts, fractures

2. caustic chemicals → acids, cleaning agents

3. ischemia or infraction → causes necrosis; necrosis triggers inflammation

4. allergic reactions

5. foreign bodies → glass, splinter

6. infection

Acute inflammation

the process of acute inflammation is the same regardless of the course

• chemical mediators are released in injury tissues, they affect BVs and nerves within the damaged area

inflammatory mediator initiate vascular phase and send signals to WBCs; causes cellular phases

Inflammation events

1. Release of chemical mediators → bradykinin is released from injured cells, this activates pain receptors; mast cells and basophils release histamine (increase membrane permeability)

2. capillary dilation and increased blood flow → chemical mediators (histamine and bradykinin) cause vasodilation and increase capillary permeability

3. chemotaxis to attract phagocytes → neutrophils and monocytes arrive to the injury site; the neutrophils and macrophages phagocytize bacteria

Monocytes

they leave the blood and goes to the tissues

• when it goes to the tissue it becomes a macrophage

Neutrophils

they do transmigration from cels and tissues; in tissues, they initiate phagocytosis to get rid of bacteria

Vascular phase of inflammation

if the injury is physical, there is brief vasoconstriction and clotting

vasodilation is triggered by chemical mediators increases the blood flow to the injury site → this is called hyperemia

inflammation causes increased vascular permeability and the leakage of exudate (exudate contains important proteins for fighting infection and for the healing process

Cellular Phase

second major step of inflammation

• it involves chemotaxis (which is the recruitment and activation of pahgocytosis in following steps)

steps:

1. rolling and margination → the phagocytes line up along the inner surface of the blood vessel wall

2. adhesion → phagocytes bind tightly to adhesion molecules

3. Transmigration (diapedesis) → squeezing through the tight gaps in vessel walls (leaving the vascular compartment and reaches tissue)

4. phagocytosis → neutrophils and macrophages engulf and destroy pathogens

Chemotaxis

phagocytes moves to the walls of capillaries

Histamine

source: mast cell granules

major action: immediate vasodilation and increased capillary permeability to form exudate

Cytokines (interleukins, lymphokines)

source: released by macrophages and lymphocytes (T-lymphocytes, macrophages)

major action: the T-lymphocytes increase plasma proteins, ESR, and the macrophages include fever, chemotaxis, and leukocytosis

Leukotrienes and prostaglandins

leukotrienes

source: synthesis from arachidonic acid in mast cells

major actions: it has a later response of vasodilation, increased capillary permeability, and chemotaxis

prostaglandins

source: synthesis from arachidonic acid in mast cells

major actions: vasodilation, increased capillary permeability, pain, fever, potentiate histamine effect

Kinins (bradykinin)

source: activation of plasma protein (kinogen), they are early response mediators and stimulates pain response

major action: vasodilation and increased capillary permeability, pain, chemotaxis

Chemical mediators of inflammation

injured cells membrane release arachidonic acid

• used for lipooxygenase → synthesizes leukotrienes, these leukotrienes induce smooth muscle contraction, constricts pulmonary airways, and increases microvascular permeability

• used for cyclooxyrgenase → synthesizes prostaglandins, these prostaglandins induce vasodilation and bronchoconstriction, inhibits inflammatory cell function

Corticosteroid medications and Benadryl

corticosteroid medications → anti-inflammatory medications

• it is better for relieving inflammation because they prevent the synthesis of arachnid acid (it produces relief of inflammation)

Benadryl → used for allergic reactions, blocks the release of histamine

local manifestations of inflammation

redness and warmth → caused by increased blood flow to damaged area

swelling → caused by increased capillary permeability (shift of protein and fluid into the interstitial space, development of exudate)

pain → increased pressure of fluid on nerves; release of chemical mediators (e.g., bradykinins)

• bradykinins cause pressure nerve endings

loss of function → edema may interfere with movement

rubor (redness), tumor (swelling), calor (heat), dolor (pain), functio laesa (loss of function)

Exudate

fluid that leaks from capillaries into interstitial spaces during inflammation, classified according the cause and type of inflammation

Serous exudate

watery, consists of primarily of fluid, some proteins, and white blood cells

• ex) blister/vesicle (watery)

caused by mechanical mechanisms

Hermorrhagic exudate

contains a significant amount of RBCs due to damage or rupture of BVs

Fibrinous exudate

contains large amounts of fibrinogen, cells and form a thick and sticky meshwork

• high fibrinogen content

Membranous or pseydomenbranous exudate

develop on mucous membrane surfaces, forms a grayish-white membrane (caused by necrosis)

• composed of necrotic cells enmeshed in a fibro-purulent exudate

Purulent or suppurative exudate

contains large amounts of pus

• thick, yellow-green, composed of leukocytes, cell debris, and microorganisms

a microscopic exam of this would show a lot of WBCs, bacteria, and dead cells

Pathogenesis of acute inflammation

come back

Systemic Manifestations of Inflammation

1. Fever (pyrexia) → common inflammation is extensive. Triggered by release of pyrogens (fever inducing mediators)

• leukocytes release pyrogens → interleukins (IL) and tumor necrosis factor (TNF)

• pyrogens reset thermoregulatory center: increase the set point to activate heat-conserving and heat-producing mechanisms (vasoconstriction, shivering, and increased metabolism)

these increase body temperature (vasoconstriction limits blood flow to surface and shivering produces movement that generates heat)

2. Malaise, headache, and fatigue → feeling unwell; interleukins (IL) and (TNF) affect CNS, this is lethargy

The course of a fever

come back

Intermittent fever

temp rises above normal for a period of time and then returns to normal

• usually normal temp in the morning and high at night

Sustained fever

temp remains above the normal temperature throughout the day with little variation

Remittent fever

temp remains above normal but fluctuates by 1 degree C during the day without returning to normal

Relapsing fever

periods of fever alternate with several days of normal temp, followed by another episode of fever

Leukocytosis

increased WBC count

• leukocytosis-inducing factors stimulate bone marrow activity and promote release of leukocytes

is a form of lab testing

Erythrocyte sedimentation rate

for of lab testing that shows elevated rate due to increased plasma proteins causing RBCs to settle faster

• infection ESR is increased (shorter time to settle down)

Differential WBC count

lab testing that shows the percentage of each type of WBCs in the blood

• helpful to distinguish between bacterial and viral infection

Circulating plasma proteins

lab testing that shows elevated circulating plasma proteins

• the liver makes C-reactive protein (CRP): normally, not found in the blood

• CRP attaches to bacteria or injured cells, functions as an opsonin

note: C-reactive proteins cannot confirm anything bc it is not specific to one type of inflammation

The course of inflammation and healing

come back

Chronic Inflammation

inflammation lasts 2 weeks or longer

• often related to an unsuccessful acute inflammatory response

• vascular phase decreases → less swelling and exudate

• more cell infiltration → presence of lymphocytes, macrophages, and fibroblasts

  • this causes continued tissue destruction, more fibrous scar tissue (replacement of functional tissue by non-functional tissue)

fibroblasts change the structural cells to immune managers that recruit WBCs that drives tissue scaring

• Granuloma may develop around foreign object

Acute inflammation

self-limited and short of duration (usually fully resolves)

• exudate formation, transmigration of neutrophils and monocytes

Chronic inflammation

self-perpetuating and may last for weeks, months, or even years (makes more phagocytic cells)

• infiltration by mononuclear cells (macrophages) and lymphocytes

• proliferation of fibroblasts: fibroblasts multiply and migrate into the injured area

Fibrosis

scar formation (fibroblasts produce new CT)

• during chronic inflammation

Chronic Inflammation

Persistence of infection, antigen, or foreign body causes

1. persistent acute inflammation

2. neutrophil degranulation and death

3. lymphocyte activation

4. fibroblast activation

all these cause:

1. lymphocyte and monocyte/macrophage infiltration (pus)

2. tissue repair (scar)

granuloma

cluster of immune cells that forms when the body attempt to wall off a foreign substance or an infectious agent that it cannot eliminate

• macrophages form giant and epithelioid cells to wall off and isolate area

• granuloma → giant and epithelioid cells surrounded by lymphocytes

Two types of granuloma

1. granuloma associated with foreign bodies (ex., splinters and sutures)

2. granuloma associated with microorganisms (ex., TB and syphilis)

ex) TB skin test if it is positive means that the patient has a granuloma in the lungs (to prevent active inflammation and spread of pathogenesis) → strong immune system

• the granuloma stays for the rest of your life but it prevents TB from becoming active

Potential complications of inflammation

infection → microorganisms can more easily penetrate edematous tissues

• some microbes resist phagocytosis

• the inflammatory exudate also provides an excellent medium for microorganisms

skeletal muscle spasm → protective response to pain

deep ulcers → result of severe or prolonged inflammation

• caused by cell necrosis and lack of cell regeneration

Labile cells

continue to divide and replicate throughout life, replacing cells that are continually being destroyed

• ex) blood cells, epithelium

Stable Cells

normally stops diving when growth ceases, but can divide when stimulated by injury

• ex) bone cells

Permanent cells

they are non-diving cells that have left the cell cycle and cannot regenerate or replicate through mitosis during postnatal life

• ex) neuron

Resolution

type of healing where the damaged cells recover

• minimal tissue damage- returning injured tissue to the original structure and function

type of healing

Regeneration

type of healing where the damaged tissue is replaced with cells that are functional

• the epidermis regenerates after superficial injury

Replacement or fibrosis

type of healing where the replacement of destroyed tissue with scar tissue (non-functional tissue)

• composed primarily of collagen to restore the strength of the tissue but not its function

ex) heart failure (myocardial infraction replacement of damaged cardiac tissue with a fibrosis scar → the myocardium loses its ability to pump blood)

• prolonged inflammation resolves by scarring

Primary intention healing

small, clean would

• wounds that heal under conditions of minimal tissue loss

faster healing

Secondary intention healing

great loss of tissue with contamination

• wounds that require a great deal more tissue replacement, more formation of scar tissue

Stages of wound healing

1. Coagulation → activation of platelets, fibrin mesh of blood clot forms; the fibrin stabilizes the clot and forms a temporary framework for healing

2. Inflammation → increased blood flow; neutrophils arrive first and remove bacteria and damaged tissue; macrophages follow and continue cleaning the would while releasing growth factors

3. Proliferation → new tissue begins to form; fibroblasts proliferate and produce collagen and extracellular matrix; angiogenesis creates new BVs (to supply tissues with nutrients and oxygen); granulation tissue develops; re-epithelization restores the surface epithelium (stem cells start to make new stem cells); the wound begins to contract

4. Remodeling (Maturation) → collagen is reorganized and strengthened; re-epithelization continues; the scar becomes smaller and stronger

Are the stages of wound healing the same for primary and secondary intention?

yes

Complications of would healing

can occur as slow, excessive, or abnormal

1. infection → bacteria enter the wound and interfere with healing

2. ulceration → wound fails to heal and remains open; common in chronic conditions such as pressure injuries and poor blood supply (also can be nutritional deficiencies, secondary)

3. excessive scar formation → hypertrophic scar: excess collagen produces a raised scar, remains within the boundaries of the original wound; keloid: excessive collagen forms a raised scar that extends beyond the original wound margins

4. adhesions → bands of scar tissue joining two surfaces that are normally separated, usually composed of abdominal surgery and pertionitis

Abdominal surgery

adhesions can form between loops of intestines or between the intestine and abdominal wall

Peritonitis

inflammation of the pertioneum can lead to extensive abdominal adhesions

hypertrophic scar

excessive collagen produces a raised scar, remains within the boundaries of the original wound

keloid

excessive collagen forms a raised scar that extends beyond the original wound margins