Understanding Inflammation

Inflammation Overview

• Inflammation developed by Albara Alomari.
• Students should read Concept 24: pages 220-227 (from Giddens) and Chapter 14: pages 225-230 (from Lewis) for preparation.
• Review of anatomy and physiology of the immune system is necessary.
• Students need to familiarize themselves with terms like acute, chronic, nonspecific response, fibrous repair, exudate, extravasation, and hyperemia.
• It is important to understand Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
• Complete interactive review questions on Evolve.
• Inflammation is an immunologic defense against tissue injury, infection, or allergy, described in Arabic as هو دفاع مناعي ضد اصابة الانسجة او العدوى او الحساسية.

Learning Outcomes

• Define and describe the concept of inflammation.
• Differentiate between acute and chronic inflammation.
• Describe the process of inflammation.
• Recognize the risk factors for inflammation.
• Recognize when an individual has inflammation.
• Provide appropriate nursing and collaborative interventions to eliminate inflammation (nursing, pharmacotherapy).
• Apply learning knowledge to case scenarios.

Key Terms

• Acute Inflammation: Describes diseases with sudden onset and a short, relatively severe course, lasting from minutes to days.
• Chronic Inflammation: Describes diseases with long duration and slow progression, involving repeated tissue destruction and repair for weeks to years after the initial injury.
• Extravasation: Refers to the leaking of substances out of their containing structure.
• During inflammation, vascular permeability increases allowing water, salts, and small plasma proteins to escape into tissues; WBCs migrate out of blood vessels via diapedesis.
• Exudate: Material consisting of serum, fibrin, and WBCs that pass out of blood vessels into an area of inflammation.
• Hyperemia: An increase in blood or blood flow to an area of the body.

Normal vs. Inflamed Vessels

• In normal conditions, blood vessels have an extracellular matrix and occasional resident lymphocytes or macrophages.
• After inflammation arterioles dilate leading to vasodilation, increased blood flow causing erythema and warmth.
• The capillary bed expands and venules also dilate.
• During inflammation leukocytes neutrophil recruitment and migration and leakage of plasma proteins occur, leading to edema.

Inflammatory Responses

• It's important to recall the difference between cellular adaptation, cellular injury, and cellular death.
• Cellular adaptation can involve hypertrophy, atrophy, or hyperplasia.
• Cell injury can be reversible or irreversible.
• After cell injury cell death and necrosis may occur.

Cell Death

• Apoptosis: This is programmed cell death and is a normal physiological process.
• Apoptosis is also referred to as cell suicide موت الخلايا المبرمج.
• Apoptosis eliminates unwanted or worn-out cells and cells produced in excess or those developed improperly.
• Apoptosis involves genetic problems but does not involve inflammation.
• Necrosis: This is not a normal process in developed tissues and is serious when many cells are involved.

Types of Injury That Cause Inflammation

• Mechanical injury, such as bone fractures, sprains, and dislocations from tripping and falling.
• Thermal injury, such as sunburn and hot fluid spills.
• Electrical injury, such as contact with a wet finger in a power outlet.
• Chemical injury, such as ingestion of bleach by children.
• Radiation injury, such as skin burns from radiation therapy.
• Biological assault, such as bacterial and fungal infections like cellulitis and athlete's foot.

Defense Against Injury

• The skin and mucous membranes
• Mononuclear phagocyte system
• Inflammatory response

Causes of Cell Injury

• Hypoxia/ischemic injury, described as نقص اكسجين او نقص تروية.
• Heat and cold
• Radiation
• Electrothermal injury
• Mechanical trauma
• Chemical injury
• Microbial injury
• Immunological factors
• Neoplastic growth.

Function of Inflammation

• An immunologic defense against tissue injury.
• Restoration of normal, functioning cells after injury.
• Restoration of normal, functioning cells after injury, described as استعادة الخلايا الطبيعية والعاملة بعد الاصابات.
• Fibrous repair occurs when restitution of functioning cells is impossible.

Types of Hypersensitivity Reactions

• Type I (Anaphylactic): Involves IgE antibodies, histamine/SRS-A mediators, examples include allergic rhinitis/asthma, and wheal/flare skin test.
• Type II (Cytotoxic): Involves IgG and IgM antibodies, complement lysis/neutrophils mediators, for example, transfusion reaction and a negative skin test.
• Type III (Immune-Complex): Involves IgG and IgM antibodies, neutrophils/complement lysis mediators, for example, Autoimmune (Systemic lupus erythematosus, Rheumatoid arthritis ), and erythema/edema in 3-8 hours skin results.
• Type IV (Delayed Hypersensitivity): Involves no antibodies it uses cytokines, T cytotoxic cells, monocytes/Macrophages/Lysosomal enzymes as mediators, e.g., contact dermatites/transplant rejection and erythema/edema in 24-48 hours (tuberculin test) skin resutls.

Comparison of Humoral and Cell-Mediated Immunity

• Humoral Immunity: Involves B lymphocytes, antibodies, present memory cells, protects against bacteria/extracellular viruses/respiratory and gastro-intestinal pathogens, with examples including anaphylactic shock, atopic diseases, transfusion reaction, and bacterial infections.
• Cell-Mediated Immunity: Involves T lymphocytes/macrophages, sensitized T cells/lymphokines, present memory cells, protects against fungi/intracellular viruses/chronic infectious agents/tumor cells, with examples including tuberculosis, fungal infections, contact dermatitis, graft rejection, and destruction of cancer cells.

Inflammatory Response Phases

• Vascular Response: Starts with vasoconstriction (by SNS) to allow platelets to seal off the injured area; Vasodilation follows (by histamine) to increase blood flow (hyperemia).
• Cellular Response: Involves the migration of neutrophils (6-12 hr), monocytes (3-7 days), and lymphocytes to the injured site.
• Basophils are released during inflammation.
• Formation of Exudate: Accumulation of fluid and cells at the inflammatory site.
• Healing: Repair of tissues.

Cardinal Signs of Acute Inflammation

• Pain
• Heat
• Redness
• Swelling
• Loss of function

Function of Inflammatory Exudates

• Transport leukocytes and antibodies
• Dilute toxins and irritating substances
• Transport nutrients for tissue repair

Types of Inflammatory Exudate

• Serous: Watery and low in protein; examples include skin blisters and pericarditis.
• Serosanguineous: Has serous and some blood in the drainage.
• Fibrinous: Thick, sticky, and high in protein, indicated by an arrow demonstrating an increase in Fibrinogen.
• Catarrhal: Cloudy mucous such as a runny nose due to a common cold.
• Purulent: Indicates infective organisms, leukocytes, and cellular debris in abscesses, boils, and cellulitis.
• Hemorrhagic: Contains red blood cells with the presence of RBC’s may lead to hematoma.

Healing Process After Injury

• Repair: Occurs by connective tissue repair.
• Regeneration: Involves replacement with cells of the same type.

Phases of Wound Healing

• Hemostasis (Day 1 to 3): Stops bleeding through vasoconstriction and platelet aggregation and thrombus formation .
• Inflammation (Day 3 to 20): Sets up a new framework for blood vessel growth and involves infiltration of neutrophils, monocytes/macrophages, and lymphocytes.
• Proliferation/Granulation (Week 1 to 6): Pulls the wound closed and involves re-epithelialization, angiogenesis, and collagen production.
• Remodeling/Maturation (Week 6 to 2 Years): Forms final proper tissue through collagen remodeling and maturation of the blood supply.

Defense Mechanisms During an Invasion

• Adaptive (acquired) Immunity: Includes cellular (cytotoxic) and humoral (antibodies) responses.
• Innate (natural) Immunity- Mechanisms of Action: Includes macrophages, neutrophils, eosinophils, basophils, monocytes, and the complement system.
• Non-specific Physical & Chemical Defenses: Consists of barriers (skin/mucous membranes/stomach acid/lysozyme in tears) and expulsion (coughing/sneezing/vomiting/diarrhea).

Question 2 Answer (Bradykinin)

• The substance primarily responsible for pain associated with inflammation is Bradykinin because it increases vascular permeability and stimulates pain receptors.
• In Arabic: لبراديكينين هو وسيط رئيسي في الاستجابة الالتهابية وهو المسؤول الأساسي عن الألم المرتبط بالالتهاب. يعمل على زيادة نفاذية الأوعية الدموية، وتوسيع الأوعية، كما يحفز مستقبلات الألم مباشرة، مما يؤدي إلى الإحساس بالألم.

Consequences of Ineffective Inflammatory Response

• Local tissue damage from compression.
• Development of chronic inflammation.
• Systemic Pathologic Responses such as استجابات مرضية جهازيه : -Atherosclerosis تصلب الشرايين -Chronic renal diseasemer مرضا لﻜی از مزمن -Neurological disorders اضطرابات عصبية

Manifestations of Inflammation

-Signs and symptoms can be: -Localized (5 cardinal signs of inflammation as well as symptoms specific to their location). -Systemic (such as Fever, neutrophilia, lethargy and muscle catabolism).

Risk Factors of Inflammation

-Populations at Greatest Risk: Very young, very old and uninsured. -Individual risk factors such as: -Autoimmune disease -Allergies -Exposure to pathogens -Compromised immunity -Chronic disease -Lack of proper sanitation -Genetic -Obesity -Factors that affect immune response!

Five Classic Signs of Inflammation & Pathophysiologic Inflammation :

• Pain.
• Swelling.
• Redness.
• Heat.
• Loss of function.
• The pathophysiologic inflammation of these signs progresses as follows: -When tissue injury occurs, proinflammatory hormones increase blood flow to the injured area. -Increased blood flow results in both redness and heat. -Swelling is the result of a combination of increased blood flow and extravasation of WBCs, fluids, and substances. -Pain results from the pressure of swollen tissues that stimulate pain receptors. -Loss of function occurs as a result of swelling.

Assessment

-Hitory: -Identify the inflammatory trigger and timeline. -Symptoms of inflammation include pain, swelling, and fatigue. -Examination: -Local manifestations: swelling, pain, heat, erythema, exudate -Systemic manifestations: fever, malaise, fatigue -Diagnostic Tests

Common Diagnostic Test

-Laboratory tests such as CBC, WBC with differential, CRP, and ESR (Increase with inflammation). -Serological tests to detect specific antibodies or viruses. -Radiographic studies (systemic) such as MRI, CAT, PET scans, Colonoscopy.

Nursing Interventions and Prevention

-Provide appropriate nursing and collaborative interventions to eliminate inflammation. -Reducing risk for injury and infection. -Maintaining good hygiene, properly using safety equipment and storing and preparing food. -Pharmacologic therapy such as: Steroids NSAIDS, Recombinant DNA, Antipyretics, Analgesics and Antimicrobials

• Steroids/Corticosteroids* -Role in Treatment: sever inflammation by suppressing chemical mediators and immune system. -Example of Drugs: Prednisone
• Nonsteroidal anti-inflammatory drugs (NSAIDs)* -Role in Treatment: Inhibit the enzyme cyclooxygenase (COX to reduce inflammation and pain. -Example of Drugs: Aspirin,and Ibuprofen
• Recombinant DNA and Monoclonal antibodies* -Role in Treatment:Systemic inflammation and treatment moderate-to-severe rheumatoid arthritis. -Example of Drugs: Infliximab
• Antipyretics* -Role in Treatment:Eliminate fever that associated with inflammation -Example of Drugs: Acetaminophen, Aspirin.
• Analgesics -Role in Treatment:Eliminate pain associated with inflammation -Example of Drugs: NO EXAMPLE
• Antimicrobials* -Role in Treatment:Inhibit growth or destroy infecting organisms causing inflammation -Example of Drugs: Keflex
• Vitamins* -Role in Treatment:Healing -Example of Drugs: A,B complex,C,D

Negative Effects of Corticosteroids

• Suppression of the normal functions of the adrenal gland
• Increase Blood Sugar
• Mood change
• Cataracts
• Peptic Ulcers
• Electrolyte imbalances
• Osteoporosis

Order of Steps for Acute Inflammatory Response

• Tissue injury occurs.
• Release of chemical mediators.
• Vasodilation and increased blood flow ensue.
• Swelling and retraction of endothelial cells takes place.
• Vascular permeability increases and small plasma proteins leakage occurs.
• "Walling off"
• Movement of immune response cells to the site of injury.
• Exudate formation happens.
• Movement of glucose and oxygen to the site needing repair.
• Release of chemical repair factors from activated endothelial cells.

Mediators of Inflammation

• Histamine: Source granules of basophils & Function is vasodilation
• Serotonin: Source is Platelets and function in Vasodilation.
• Kinins (e.g., bradykinin): Source is Factor kininogen and Function is Smooth muscle contract.
• **Complement components (C3a, C4a, C5a) Source is Agents complement pathway and Function is Histamine release.
• **Fibrinopeptides Source is Agents clotting system and Function is Vascular permeability.
• Prostaglandins and leukotrienes:; Source is Arachidonic acid and Function is vasodilation .
• Cytokines: Source is Blood cells and function in messengers.

Manifestations of Inflammation Clinical Case

-Mr. Fred Roger, a 58-year-old man, is admitted to the hospital emergency due to burns, he showed signs of clinical manifestations of inflammation, here are the physiological mechanisms.

• The patient also has a leg with is infection.
• elevated temperature and elevated WBC count with an increase in bands.
• The patient has Fever, caused by:
• Fever activates the body's defence mechanisms by.
• Increased killing of microorganisms.
• Increased phagocytosis & T cells proliferation, .
• Increased proliferation of T cells.
• Possible enhanced activity of various cytokines, including interferons.
• He also has a local manifestation of the inflammatory process (swelling of his throat) which is causing him to have a hoarse voice and irritated throat.
• It would also be expected that Mr. Roger's wounds would manifest the local signs of inflammation of redness, heat, swelling, pain, and loss of function.

Mr. Roger's Risk Factors for Developing a Pressure Injury.

• Older age.
• Elevated body temperature.
• Immobility.
• Impaired circulation.
• Pain.
• Prolonged surgery.