Chapter 9: Davis Advantage for Pathophysiology inflammation and wound healing

Inflammation

A protective, coordinated response of the body to an injurious agent. It involves many cell types and inflammatory mediators that initiate, modulate, amplify, and terminate this response.

a) Characteristic cellular products, tissue changes, and systemic responses are associated with inflammation.

*Intensity of the inflammatory reaction is usually proportional to the extent of the tissue injury.

b) major aims of inflammation are to wall off the area of injury, prevent spread of the injurious agent, and bring the body's defenses to the region under attack.

Acute inflammation triggers

various injurious stimuli, such as infections, microbial toxins, physical injury, surgery, cancer, chemical agents, tissue necrosis, foreign bodies, and immune reactions.

Three Main Stages of acute inflammation

Vascular permeability

Cellular chemotaxis

Systemic responses

Vascular permeability

vascular phase at a site of inflammation, inflammatory mediators such as histamine and bradykinin cause the blood vessels to dilate and become more permeable. This permits fluids, WBCs, and platelets to travel to the site of injury or infection. Vasodilation of the arterioles is followed by enhanced capillary permeability, allowing fluid to flow out of the blood vessels to the injured tissues

Purulent exudate (pus)

fluid is rich in protein from WBCs, microbial organisms, and cellular debris

Abscess:

localized, walled-off collection of purulent exudate within tissue

Transudate

fluid that contains little protein and is mainly a watery filtrate of blood

Effusion

Any accumulation of fluid in a body cavity

*due to inflammatory or non-inflammatory processes.

Chemotaxis

Cell movement that occurs in response to chemical stimulus: a chemical signal from microbial agents, endothelial cells, and WBCs attracts platelets and other WBCs to the site of injury

Leukocytosis

Increase in the number of white blood cells release by bone marrow into blood

leukemoid reaction

Exaggerated WBC response to infection

ex. Leukemia

Cytokines

Inflammatory mediators (Chemicals) released by the immune system (WBC) communicate with the brain.

Modulate the inflammatory reaction by amplifying or deactivating the process. Also cause localized and systemic effects.

tumor necrosis factor (TNF) alpha

Origin: Macrophage

Effects: Fever, lack of appetite, raises metabolism to cause cachexia, hypotension

interleukins (ILs)

Origin: Macrophage

Effects: Fever, stimulates platelet production, fatigue, anemia, headache

Chemokines

proteins that attract leukocytes to the endothelium at the area of injury.

acute phase proteins

liver proteins that facilitate WBC phagocytosis of microbes and other foreign material and assist in the analysis of the inflammation process occurring in the body.

ex. C-reactive protein (CRP), fibrogen, serum amyloid A, and hepcidin

C-reactive protein (CRP)

a key acute phase protein that is integral to marking foreign material for phagocytosis; activating the complement system, which augments immunity; and stimulating other inflammatory cytokines.

Elevated:

-in the bloodstream indicates that active inflammation is occurring

-of a specific type of CRP, identified by a laboratory test called high sensitivity CRP, is a marker for increased risk of myocardial infarction in patients with coronary artery disease.

Fibrinogen

Binds to red blood cells (RBCs) and fixes them into stacks that precipitate rapidly in the blood through processes called rouleaux and sedimentation

erythrocyte sedimentation rate (ESR)

Laboratory test that, if elevated, indicates actively occurring inflammation. This can assist the clinician to determine if the patient is currently enduring an active process of inflammation.

Histamine

inflammatory mediator

Origin: Mast cells, Basophils, platelets

Effects: Vasodilation, increases vascular permeability, activates endothelium

Kinins

Origin: Liver, lungs, kidneys

Effects: Increased vascular permeability, smooth muscle contraction, pain, natriuresis, hypotension

Platelet-activating factor

Origin: Platelets, leukocytes, mast cells

Effects;Vasodilation, increases vascular permeability, platelet aggregation, angiogenesis (formation of new blood vessels), leukocyte adhesion to endothelium

Prostaglandins

inflammatory mediator

Origin: Leukocytes

Effects:Pain, fever, vasodilation, muscle spasm

*Two different enzymes are involved in the formation of PGs from arachidonic acid: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Each pathway yields a different type of PG.

Leukotrienes

Origin: Leukocytes, mast cells

Effects: Bronchospasm, increased vascular permeability

Substance P

Origin: Neurons

Effects: Pain, hypotension, enhances vascular permeability

5 Types of White Blood Cells.

neutrophils, eosinophils, basophils, lymphocytes, monocytes

Phagocytosis

recognition and attachment of the leukocyte to the foreign matter, engulfment, and degradation or killing of the ingested matter (

white blood cell (WBC) differential

used in the diagnosis of infection and inflammation.

This test is part of a complete blood count (CBC) with differential, which quantifies RBCs and WBCs.

WBC with differential measures the total number of WBCs and calculates the percentages of specific types of WBCs within the total. T

result of the laboratory test shows the predominate type of WBC responding to the infectious agent and can be used to indicate the etiology of inflammation.

Systemic Responses.

fever

pain

general malaise

lymphadenopathy

anorexia

sleepiness

lethargy

anemia

weight loss

pyrogens

substances that cause fever

lymph nodes

Bean-shaped filters that cluster along the lymphatic vessels of the body. They function as a cleanser of lymph as wells as a site of T and B cell activation

Lymphocytes

The two types of white blood cells that are part of the body's immune system:

B lymphocytes form in the bone marrow and release antibodies that fight bacterial infections;

T lymphocytes form in the thymus and other lymphatic tissue and attack cancer cells, viruses, and foreign substances.

3 Outcomes of Acute Inflammation

1. Complete resolution

2. Healing by connective tissue

3. Chronic, persistent inflammation that does not recede

Chronic Inflammation

continuous injury or irritation to tissue

Causes of chronic inflammation include:

• Persistent infection by microorganisms that are difficult to eradicate (e.g., TB).

• Hypersensitivity disorders, which cause excessive activation of the immune system. Examples of these disorders include autoimmune diseases such as RA, multiple sclerosis (MS), or systemic lupus erythematosus (SLE).

• Prolonged exposure to potentially toxic agents such as coal dust, which causes anthracosis (black lung).

Granuloma

an area where macrophages have aggregated and are transformed into epithelial-like or epithelioid cells.

A granular tumor or growth

Wound healing can be divided into 4 phases:

1. Hemostasis

2. Inflammation

3. Proliferation, granulation tissue formation, angiogenesis, and epithelialization

4. Wound contraction and remodeling

Fibroblasts

In connective tissue, cells that synthesizes collagen and provides the extracellular matrix in wound healing, is the key cell involved in this process

Angiogenesis

Vascular endothelial cells create new blood vessels

Primary intention healing

tissue surfaces are approximated (closed) and there is minimal or no tissue loss, formation of minimal granulation tissue and scarring

Secondary intention healing

wound in which the tissue surfaces are not approximated and there is extensive tissue loss; formation of excessive granulation tissue and scarring

Tertiary intention healing

Wound is left open for 4-5 days to allow edema or infection to resolve

Factors Involved in Wound Healing

Nutrition

Oxygenation

Circulation

Immune strength

Diabetes; weakens healing

Use of corticosteroids; diminishes healing

Use of immunosuppressant agents

Contamination

Surgically inserted devices

Obesity

Age

nitrogen balance

difference between nitrogen intake and nitrogen excretion.

Protein is the best source of nitrogen in the diet.

When a patient's nitrogen intake exceeds nitrogen excretion, the resultant positive nitrogen balance suggests the availability of protein for wound repair.

foreign bodies

Viruses, intracellular bacteria, dust particles, and other debris phagocytized by a cell

mechanical factors

skin, mucous membranes, ciliary escalator lungs, lacrimal apparatus, saliva, urine, and vaginal secretions