Davis Advantage Chapter 9 Vocabulary & Topics

Pyrogens

Microbial organisms, bacterial products, and cytokines all act as pyrogens, which are substances that cause fever. Pyrogens activate PGs to reset the hypothalamic temperature-regulating center in the brain to a higher level. A higher body temperature is theorized to increase the efficiency of WBCs in their defense of the body against foreign invaders (see Fig. 9-3).

Prostaglandins (PGs)

Prostaglandins (PGs) are released from WBCs and other cell membranes through a series of reactions.

1. complete resolution

Resolution involves normalization of vascular permeability, deactivation of chemical mediators, elimination of cellular debris and edema, and apoptosis of WBCs.

Leukopenia

Leukopenia is a term used to indicate too few WBCs.

Factors involved in Wound Healing

• Nutrition: Lack of adequate nutrients, particularly protein, decreases cellular regeneration and metabolic function. • Oxygenation: Oxygen is needed for neutrophil phagocytosis and collagen synthesis. • Circulation: Lack of adequate circulation predisposes the individual to ischemia, infarction, and consequent infection of necrotic tissue, also known as gangrene. • Immune strength: Diabetes, corticosteroid use, cancer, human immunodeficiency virus, and immunosuppressant agents diminish WBC activity, delay wound healing, and predispose to infection. Contamination: Foreign bodies present in a wound diminish healing ability and predispose to infection. Sutures that remain too long can act as foreign bodies and inhibit healing. Surgically inserted devices such as pacemakers, heart valves, and orthopedic or prosthetic implants can become sources of infection and predispose the patient to septicemia. • Obesity: Adipose tissue does not heal efficiently and approximated edges cannot be sutured together easily. • Age: The regeneration process of infants and young children is superior to that of adults. Studies show that fetal wounds heal without fibrosis or scarring. Elderly adults have the slowest healing process.

(Systemic Response) Fever

(1) Fever. Fever, an increase in body temperature, is a common manifestation of inflammation and infection. (2) Note pyrogens (3) Fever, although advantageous to the immune system, can reach levels high enough to cause seizures and brain damage. (4) The sensation of chills often accompanies fever. (5) The sensation of cold and muscle shivering are experienced as chills, which continue until the body reaches the higher hypothalamic temperature set-point.

(Systemic Response) Lymphadenopathy

(1) Lymphadenopathy, or lymphadenitis, is a term used to describe the enlargement of lymph nodes because of inflammatory processes. (2) Notes Lymph nodes and lymphocytes (3) Because of the active proliferation of lymphocytes, lymph nodes enlarge and become tender. Lymphatic fluid or lymph circulates around body tissues and collects debris from the tissues.

(Cellular Chemotaxis) Types of White Blood Cells Cont'd

(1) Neutrophils are also referred to as polymorphonuclear leukocytes (PMNs); in their immature form, they are called bands or stabs. (2) Neutrophils, basophils, and eosinophils are referred to as granulocytes because they contain obvious cytoplasmic granules when examined under the microscope. These cytoplasmic granules contain important enzymes and inflammatory mediators to support the inflammatory process and fight infection. Mature neutrophils also have multisegmented nuclei and are sometimes known as segmented neutrophils (segs). (3) A large inflammatory response creates an urgent need for WBCs at the site. Neutrophils, which are the first responders, rush to the site within the first 24 to 48 hours. They begin the process of phagocytosis of the foreign matter immediately.

Primary, Secondary, and Tertiary Intention

(1) Skin wounds heal by either of three processes: primary, secondary, or tertiary intention (see Fig. 9-8). (2) Note Primary intention, secondary intention, teritary intention

Inflammatory Conditions

- Appendicitis: inflammation of the appendix - Hepatitis: inflammation of the hepatocytes or liver - Colitis: inflammation of the colon - Arthritis: inflammation of arthrus tissue or joints.

Labile Cells

1. Cells that continuously proceed through the cell cycle are called labile cells. 2. Labile cells continually divide and replicate throughout life, replacing cells that are constantly eliminated. For example, skin, oral mucosal cells, gastrointestinal mucosal lining cells, and genitourinary mucous membrane cells are continuously sloughed and require replacement. 3. The bone marrow is continuously active as it synthesizes blood cells. Cancer cells are considered labile cells because they are constantly dividing.

Chronic Inflammation Cont'd

Autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are chronic inflammatory disorders. In autoimmune disease, an unknown offending agent, also called an antigen, incites an inflammatory reaction that initiates production of antibodies that attack the body's own tissues. The antibodies produce a persistent inflammatory reaction that causes chronic tissue damage.

The acute inflammatory reaction involves three main stages:

1. vascular permeability 2. cellular chemotaxis 3. systemic responses.

Chronic Inflammation Cont'd

A granuloma is an area where macrophages have aggregated and are transformed into epithelial-like or epithelioid cells. TB is the prototypical granulomatous chronic inflammatory disease. On histological examination of the lungs, a TB granuloma is characterized by an aggregate of macrophages surrounding mycobacteria tuberculi bacterial organisms. After acute infection, neutrophils and monocytes surround but cannot kill TB bacteria. The WBCs attracted to the area of infection can only wall off the bacteria. Eventually this region, infiltrated with macrophages, becomes a chronic inflammatory granuloma called a tubercle. The tubercle can be identified on histological examination and x-ray of the lungs (see Fig. 9-6).

Granuloma

A granuloma is an area where macrophages have aggregated and are transformed into epithelial-like or epithelioid cells. The epithelioid cells are surrounded by lymphocytes, fibroblasts, and connective tissue. Frequently, the epithelioid cells fuse to form giant cells within the granuloma.

White blood cell (WBC) differential

A laboratory test called a white blood cell (WBC) differential is used in the diagnosis of infection and inflammation. A WBC with differential measures total number of WBCs and calculates the percentages of specific types of WBCs within the total. The 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. For example, a patient with pneumonia who has an elevated total WBC count of 16,000 with 90% neutrophils most likely has a bacterial pneumonia, whereas a patient with pneumonia and an elevated WBC with 90% lymphocytes most likely has a viral pneumonia.

(Cellular Chemotaxis) Types of White Blood Cells Cont'd

A laboratory test called a white blood cell (WBC) differential is used in the diagnosis of infection and inflammation. The WBC count with differential can also indicate an acute inflammatory reaction by quantifying the number of bands in the bloodstream. When a high number of bands are present, clinicians often use the phrase "shift to the left," indicating an increase in newly formed neutrophils. An elevated WBC count with a "shift to the left" indicates that an acute inflammatory process is occurring.

Acute Inflammation

Acute inflammation can be triggered by various injurious stimuli, such as infections, microbial toxins, physical injury, surgery, cancer, chemical agents, tissue necrosis, foreign bodies, and immune reactions. Regardless of etiology, all acute inflammatory reactions cause the same characteristic vascular, cellular, and systemic changes.

Outcomes of Acute Inflammation

Acute inflammation will result in one of three outcomes: 1. complete resolution 2. healing by connective tissue 3. chronic, persistent inflammation that does not recede.

C-reactive protein (CRP)

Acute phase proteins include C-reactive protein (CRP), fibrinogen, serum amyloid A, and many other substances. These proteins influence the inflammatory process by stimulating, modulating, and deactivating the reaction. The acute phase proteins, just as cytokines, initiate, amplify, or sustain the inflammatory process, and some exert negative, dampening effects. CRP is a key acute phase protein secreted by the liver that is both proinflammatory and anti-inflammatory in action. It is integral to identifying foreign material for the immune system, activates the complement system, stimulates other inflammatory cytokines, and prevents WBC adhesion to endothelium. An elevated-level CRP in the bloodstream indicates active inflammation.

Chronic Inflammation

An inflammatory reaction that persists for a prolonged time, from weeks to months, without resolution or healing is considered a chronic inflammatory disorder.

Erythrocyte sedimentation rate (ESR)

Another laboratory test that is used to diagnose inflammation is erythrocyte sedimentation rate (ESR), which is a measure of the rate at which red blood cells (RBCs) precipitate out of the plasma; it is influenced by fibrinogen levels in the blood. Because fibrinogen levels in the blood can now be measured directly, ESR is considered an imprecise indicator of inflammation. However, ESR is still commonly used for monitoring the activity of many inflammatory diseases.

2. healing by connective tissue

At times, severe tissue injury and a large acute inflammatory reaction preclude the regeneration of normal cells. This happens when inflammation involves tissues incapable of regenerating cells or when inflammatory exudates and cellular debris cannot be adequately cleared at the conclusion of the inflammatory reaction. At these times, resolution and healing occur through the proliferation of connective tissue. Cellular debris and exudates are reabsorbed and fibrous scar tissue, rather than regenerated cells, replace damaged cells.

Chemotaxis

During the cellular phase of inflammation, a chemical signal from microbial agents, endothelial cells, and WBCs attracts platelets and other WBCs to the site of injury. This is referred to as chemotaxis.

Cellular Chemotaxis

During the cellular phase of inflammation, a chemical signal from microbial agents, endothelial cells, and WBCs attracts platelets and other WBCs to the site of injury. This is referred to as chemotaxis. Once the WBCs arrive at the site of inflammation, they line up along the endothelium in the area of inflammation in a process called margination. Some mediators amplify the inflammatory process, some attract more WBCs to the area of injury, and others attempt to stop the inflammatory process.

Vascular Permeability

During the vascular phase at a site of inflammation, inflammatory mediators such as histamine and bradykinin enable the blood vessels to dilate and become more permeable. This permits fluids, WBCs, and platelets to travel out 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 (Fig. 9-1). The increased fluid in the tissues dilutes the toxin and lowers the pH of the surrounding fluids so they are not conducive to microbial growth. The inflamed area immediately starts to become congested, warm, red, and swollen from the vasodilation and fluid extravasation into the tissues from the capillaries.

The Cell Cycle Cont'd

Each of these cell types are in a different stage within the cell cycle. These stages are: • G0: Cells are resting or quiescent and not undergoing mitotic division. • G1: Cells enter the cell cycle during this stage, where they make preparations for mitosis and then continue on to the S phase. • G2: Cells continue to undergo necessary activities before mitosis. • S: Cells undergo chromosomal duplication in preparation for mitotic division. • M: Cell completes mitosis and divides to regenerate itself.

3. chronic, persistent inflammation that does not recede.

Finally, there are times when acute inflammation cannot be resolved because of persistence of the injurious agent or other interference with healing. In these cases, inflammation becomes a chronic, persistent condition with failure to resolve and extensive tissue damage.

Transudate

Fluid that contains little protein and is mainly a watery filtrate of blood is called transudate.

Primary intention

Healing by primary intention, also called primary union, is the least complicated type of wound repair. The edges of the wound are clearly demarcated, cleanly lacerated, easily brought together, and there is no missing tissue within the injured area. A surgical wound is the best example of this type of injury, which usually undergoes a simple, rapid healing process.

(Systemic Response) Histamine Release

Histamine is an inflammatory mediator released from basophils, platelets, and mast cells, and it has many systemic effects. It causes arteriolar vasodilation, large artery vasoconstriction, and increased permeability of venules.

Histamine

Histamine is an inflammatory mediator released from basophils, platelets, and mast cells, and it has many systemic effects. It causes arteriolar vasodilation, large artery vasoconstriction, and increased permeability of venules.

Purulent exudate

If the fluid is rich in protein from WBCs, microbial organisms, and cellular debris, it is called purulent exudate, or pus

Wound evisceration

In rare cases, internal tissues and organs can extrude from the open wound, a condition called wound evisceration.

Tertiary intention

In tertiary intention, also called tertiary union, the wound is missing a large amount of deep tissue and is contaminated. It is cleaned and left open for 4 to 5 days before closure. The wound may require temporary packing with sterile gauze and have extensive drainage. By the fifth day, WBC phagocytosis of contaminated tissues occurs and the processes of epithelialization, collagen deposition, and maturation take place. Foreign materials are walled off by macrophages and other types of leukocytes to form granulomas. There is prominent scarring with healing. Commonly this type of wound requires a skin graft.

Inflammation

Inflammation is 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. There are characteristic cellular products, tissue changes, and systemic responses associated with inflammation.

Contracture

Inflexible shrinkage of wound tissue that pulls the edges toward the center of the wound

Possible Complications of Wound Healing

Keloid: hyperplasia of scar tissue, wound healing can be complicated by hyperplastic epithelialization and collagen formation. The excessive accumulation of epithelium and collagen can form a hypertrophic scar, also called a keloid. Contractures: inflexible shrinkage of wound tissue that pulls the edges toward the center of the wound. Contractures often occur in burn wounds and limit mobility when they occur across a joint surface. Dehiscence: opening of a wound's suture line Evisceration: opening of wound with extrusion of tissue and organs Stricture: an abnormal narrowing of a tubular body passage from the formation of scar tissue (e.g., esophageal stricture) Fistula: an abnormal connection between two epithelium-lined organs or vessels that normally do not connect (e.g., Tracheoesophageal fistula) Adhesions: internal scar tissue between tissues or organs. These bands of scar tissue can limit mobility if they form within a joint as in adhesive capsulitis of the shoulder (frozen shoulder).

Leukocytosis

Leukocytosis. In the cellular phase of inflammation, there is an increase in the number of WBCs released from the bone marrow into the bloodstream. WBCs are also known as leukocytes, and an elevated number of WBCs in the bloodstream is known as leukocytosis.

Lymph node

Lymph nodes are small bean-sized masses of tissue located in various regions of the body, including the neck, axillary regions, central thoracic region, inguinal areas, and gastrointestinal tract.

Lymphocytes

Lymphocytes mature within a lymph node, and during an inflammatory process, lymph nodes become enlarged (Fig. 9-5). Because of the active proliferation of lymphocytes, lymph nodes enlarge and become tender. Lymphatic fluid or lymph circulates around body tissues and collects debris from the tissues.

Cellular Regeneration, Tissue Repair, and Healing

Optimal regenerative healing occurs when injured cells are replaced by cells of the same type, leaving no trace of residual injury. Certain tissue injuries, such as those involving loss of tissue because of gouging injuries, cannot heal by cellular replacement. In situations such as this, cells are replaced by connective tissue, which leaves a scar.

Permanent Cells

Permanent cells cannot regenerate and therefore do not enter the cell cycle. Neurons and cardiac myocytes are considered permanent cells that do not undergo mitosis and have lost the ability to proliferate. For example, brain cells involved in stroke and myocardial cells involved in infarction are considered dead and unable to function.

Systemic Response

Persons enduring acute inflammation experience symptoms throughout the whole body, known as systemic responses, such as fever, pain, lymphadenopathy (swollen lymph nodes), anorexia, sleepiness, lethargy, anemia, and weight loss. Chemical mediators produced during the inflammation reaction are responsible for many of these systemic effects. Prostaglandins (PGs), leukotrienes, TNF-alpha, and ILs are inflammatory mediators released from WBCs.

(Systemic Response) Effects of Prostaglandins, Leukotrienes, and Their Enzymatic Pathways

Prostaglandins (PGs) and leukotriene synthesis pathways within the WBC. Injury stimulates inflammation, which attracts WBCs to the area of injury. Within the WBC, phospholipase acts upon phospholipids to yield arachidonic acid, which is then converted to PGs via the cyclooxygenase 1 or cyclooxygenase 2 pathway or to leukotrienes via the lipooxygenase pathway. The PGs created by the cyclooxygenase 1 pathway are needed to secrete gastric mucus and enhance renal perfusion and thrombus formation. The PGs created by the cyclooxygenase 2 pathway cause uncomfortable symptoms of inflammation, such as fever, edema, and pain. Leukotrienes cause bronchospasm and bronchiole edema.

Interleukins (ILs)

Some of the inflammatory mediators released by WBCs are referred to as cytokines; these include tumor necrosis factor (TNF-alpha) and interleukins (ILs). Cytokines modulate the inflammatory reaction by amplifying or deactivating the process.

Cytokines

Some of the inflammatory mediators released by WBCs are referred to as cytokines; these include tumor necrosis factor (TNF-alpha) and interleukins (ILs). Cytokines modulate the inflammatory reaction by amplifying or deactivating the process. Simultaneously, they cause localized and systemic effects. One of the systemic effects of cytokines is stimulation of the liver to release substances called acute phase proteins. Acute phase proteins include C-reactive protein (CRP), fibrinogen, serum amyloid A, and many other substances. These proteins influence the inflammatory process by stimulating, modulating, and deactivating the reaction. The acute phase proteins, just as cytokines, initiate, amplify, or sustain the inflammatory process, and some exert negative, dampening effects.

Stable Cells

Stable cells are cells that are in a resting stage until stimulated, when they then enter the cell cycle. Examples of stable cells are bone cells and hepatocytes. Both of these kinds of cells require major stimuli to enter the cell cycle, undergo mitosis, and regenerate. After fracture, bone cells enter the cell cycle to regenerate and repair bone tissue. Hepatocytes undergo mitosis and regenerate the liver after surgical, traumatic, or chemical injury.

Stricture

Stricture: an abnormal narrowing of a tubular body passage from the formation of scar tissue (e.g., esophageal stricture)

Phagocytosis

The WBCs surround and consume the foreign material in a process called phagocytosis.

Vascular Permeability Cont'd

The classic external signs of inflammation are known as the five cardinal signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and loss of function.

Chronic Inflammation Cont'd

The destructive macrophage products include free radicals, proteases, cytokines, angiogenesis growth factors, and fibroblast activators. Tissue is repeatedly damaged, healing is delayed, and connective tissue replaces injured cells. As tissue damage causes cell death, necrotic tissue stimulates an inflammatory reaction. As a result, tissues undergoing chronic inflammation can have regions demonstrating acute inflammation as well.

(Cellular Chemotaxis) Cytokines and Acute Phase Proteins

These proteins influence the inflammatory process by stimulating, modulating, and deactivating the reaction. The acute phase proteins, just as cytokines, initiate, amplify, or sustain the inflammatory process, and some exert negative, dampening effects. CRP is a key acute phase protein secreted by the liver that is both proinflammatory and anti-inflammatory in action. It is integral to identifying foreign material for the immune system, activates the complement system, stimulates other inflammatory cytokines, and prevents WBC adhesion to endothelium.

Vascular Permeability Cont'd

The fluid that leaves the capillaries is a protein-rich filtrate of blood that contains WBCs. The WBCs surround and consume the foreign material in a process called phagocytosis. As the WBCs perform defensive activities, the fluid increases within the tissue spaces and causes edema, or swelling. Note: Purulent exudate, transudate

Inflammation and the Inflammatory Response

The inflammatory response is a multistaged process that involves vascular and cellular changes, but may also include systemic changes. White blood cells (WBCs) are brought to the damaged area, and they secrete substances that control the process from initial injury to resolution or long-term inflammation. The inflammatory response is most efficient when it rids the body of injury, enhances healing processes, and resolves

(Cellular Chemotaxis) Types of white Blood Cells

There are five basic types of WBCs: 1. neutrophils 2. lymphocytes 3. eosinophils 4. basophils 5. monocytes (see Fig. 9-2).

The Cell Cycle

There are three types of body cells that differ according to their ability to regenerate: labile, stable, or permanent cells.

Types of Inflammation

There are two types of inflammation: acute and chronic. Acute inflammation occurs rapidly in reaction to cell injury, rids the body of the offending agent, enhances healing, and terminates after a short period, either hours or a few days. Chronic inflammation occurs when the inflammatory reaction persists, inhibits healing, and causes continual cellular damage and organ dysfunction. In some disorders, such as rheumatoid arthritis, tuberculosis (TB), and atherosclerosis, inflammation can persist and ultimately cause unremitting damaging effects on the body; these are considered chronic inflammatory conditions.

Wound dehiscence

When previously closed wound edges open and rupture, the condition is called wound dehiscence.

Secondary intention

When there is extensive loss of tissue within a wound, the repair process is more complex; in this case, secondary intention, also called secondary union, healing begins (see Fig. 9-8). Regeneration of the same cells to replace lost tissue is not possible. Abundant granulation and fibrous tissue is necessary to fill the defect and restore the original structure of tissue. The inflammation process within this type of wound is more intense and longer in duration. The formation of granulation tissue requires extensive time and support for the healing process.

Normal Wound Healing

Wound healing is divided into three phases: 1. inflammation 2. proliferation, granulation tissue formation, and epithelialization 3. wound contraction and remodeling. Inflammation occurs in the acute phase immediately after injury, and has been described previously. In the subsequent proliferation phase, granulation tissue forms. The fibroblast, a connective tissue cell that synthesizes collagen and provides the extracellular matrix in wound healing, is the key cell involved in this process. As early as 24 to 48 hours after injury, fibroblasts and vascular endothelial cells form the granulation tissue that serves as the foundation of scar tissue. The granulation tissue then secretes growth factors and cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), tissue growth factor-beta (TGF-beta), and interleukin-1 (IL-1). Also during this phase, epithelial cells migrate and proliferate to form a new surface and fill in the gap between the wound edges.