NR283 Pathophysiology - Week 2: Inflammation, Healing, Skin Integrity, Infection, Immunity

Inflammation and Healing

• Purpose of Inflammation:
  • Protect from infection.
  • Assist healing.
  • Remove damaged cells.
  • Repair damage.
  • Identify self from non-self.
• Causes of Inflammation:
  • Direct physical damage (e.g., cut, sprain).
  • Caustic chemicals (e.g., acid, drain cleaner).
  • Ischemia or infarction (tissue death due to inadequate blood supply).
  • Allergic reactions.
  • Extremes of heat or cold.
  • Foreign bodies (e.g., splinter, glass).
  • Infection.
• Body’s Defense Strategy:
  • First line: Physical barriers (skin, mucus membranes, tears, saliva, gastric juices).
  • Second line: Non-specific defense (phagocytosis and inflammation; macrophages, neutrophils, mast cells).
  • Third line: Specific defense (specific antibodies or cell-mediated immunity; T cells, B cells, NK cells, antibodies/antigens).
• Leukocytes (The Players):
  • Neutrophils.
  • Eosinophils.
  • Basophils.
  • Monocytes (Macrophages).
  • Lymphocytes.
  • Platelets.
  • Mast cells: Release chemical mediators like Histamine in connective tissue.

The Defense Lines and A-Team

• 1st Line: Tech Support
  • Complement System
  • Clotting Cascade
  • Kinin System
• 2nd Line: The A-Team
  • Neutrophils
  • Macrophages
  • Platelets
  • Mast Cells

Chemical Mediators

• Tools used in the inflammatory response:
  • Histamine
  • Prostaglandins
  • Leukotrienes
  • Bradykinin
  • Cytokines
  • Chemotactic factors
  • Platelet-activating factor
• Functions:
  • Activate Systems.
  • Recruit immune cells through chemotaxis.
• Source and Major Actions of Chemical Mediators:
  • Histamine:
    • Source: Mast cell granules
    • Major Action: Immediate vasodilation and increased capillary permeability to form exudate
  • Chemotactic Factors:
    • Source: Mast cell granules
    • Major Action: Attract neutrophils to site
  • Platelet-Activating Factor (PAF):
    • Source: Cell membranes of platelets
    • Major Action: Platelet aggregation; Activate neutrophils
  • Cytokines (Interleukins, Lymphokines):
    • Source: T lymphocytes, Macrophages
    • Major Action: Increase plasma proteins, ESR, induce fever, chemotaxis, leukocytosis
  • Leukotrienes:
    • Source: Synthesis from arachidonic acid in mast cells
    • Major Action: Later response: vasodilation and increased capillary permeability, chemotaxis
  • Prostaglandins:
    • Source: Synthesis from arachidonic acid in mast cells
    • Major Action: Vasodilation, increased capillary permeability, pain, fever, potentiate histamine effect
  • Kinins (e.g., bradykinin):
    • Source: Activation of plasma protein (kinogen)
    • Major Action: Vasodilation and increased capillary permeability, pain, chemotaxis
  • Complement System:
    • Source: Activation of plasma protein cascade
    • Major Action: Vasodilation and increased capillary permeability, chemotaxis, increased histamine release

Steps of the Inflammatory Response

1. Injury
2. Cells release chemical mediators.
3. Vasodilation - increased blood flow.
4. Increased capillary permeability (protein and water leave capillary - form exudate).
5. Leukocytes move to site of injury (chemotaxis).
6. Phagocytosis - removal of debris in preparation for healing.

• Normal Fluid Shift:
  • Water, electrolytes, glucose into interstitial fluid.
  • Protein remains in blood.
• Inflammation Fluid Shift:
  • Protein and water leave capillary to form exudate.
  • Water, electrolytes and protein enter interstitial fluid
• Chemotaxis
  • Leukocyte migration to injury site driven by chemotactic factors.
• Phagocytosis
  • Macrophages engulf debris.
• Activation of pain receptors by bradykinin.
• Mast cells and basophils release histamine causing increased blood flow and capillary dilation.

Complementary Pathways

• Clotting cascade: Involves plasma proteins, fibrin, fibrinogen.
• Complement system: Cascade of reactions amplifying the immune response; involves C1-9, activated by antibodies and cytokines.

Exudate

• Fluid that leaks out of blood vessels into nearby tissues, made of cells, proteins, and solid materials.
  • Serous: Watery, consists primarily of fluid, some proteins, and white blood cells.
  • Fibrinous: Thick, sticky, high cell and fibrin content, leads to scar tissue.
  • Purulent: Thick, yellow-green, contains more leukocytes, cell debris, and microorganisms, indicates bacteria.
  • Abscess: Localized pocket of purulent exudate in solid tissue.
  • Hemorrhagic: Present when blood vessels are damaged, bright red.
• Serosanguineous Exudate:
  • Thin & Watery with Light Red or Pink Hue
  • Most Common Exudate, Usually Indicative Of Damage To Capillaries, Can Become Damaged During Wound Care
• Serous Exudate:
  • Clear, Thin, & Watery Fluid
• Sanguineous Exudate:
  • Bright, Red, Fresh Blood (May Be Hemorrhagic)
• Purulent Exudate:
  • Thick, Opaque, & Odorous Build-Up from Infection

Signs of Local Inflammation and Infection

• Redness (Erythema): Caused by increased blood flow to the damaged area.
• Swelling (Edema): Shift of protein and fluid into the interstitial space.
• Pain: Increased pressure of fluid on nerves, release of chemical mediators (e.g., bradykinins).
• Heat: Caused by increased blood flow to damaged area
• Loss of function: May develop if cells lack nutrients; edema may interfere with movement. Possible exudate (especially purulent with bacterial infection).

Systemic Effects of Acute Inflammation

• Fever (pyrexia): Common if inflammation is extensive; release of pyrogens.
• Malaise: Feeling unwell.
• Fatigue and weakness.
• Headache.
• Nausea/Anorexia.

Chronic Inflammation

• Prolonged acute inflammation or chronic irritation.
• Decreased swelling.
• Increased leukocytes and fibroblasts.
• Tissue damage, fibrous scar tissue.
• Impaired cell replication.
• Increased risk of injury, disease, cancer.

Treatment of Inflammation

• Acetylsalicylic acid (ASA) / Aspirin.
• Acetaminophen / Tylenol.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) / Ibuprofen.
• Glucocorticoids / Corticosteroids.

Course of Inflammation and Healing

1. Injury and inflammation.
2. Granulation and epithelial tissue growth.
3. Scar.

• Acute Inflammation:
  • Vasodilation and increased blood flow (hot, red).
  • Release of chemical mediators (histamine, kinins, prostaglandins).
  • Increased capillary permeability (edema, pain).
  • Chemotaxis (WBC to area).
  • Irritation of nerve endings (pain).
  • Clot and fibrin mesh walls off area.
  • Phagocytosis (remove cause and cell debris).
• Resolution: Damaged cells recover.
• Regeneration: Replacement by same type of cell.
• Healing: Leads to scar tissue (fibrosis).
• If cause persists: Chronic inflammation.

Types of Healing

• Resolution: Damaged cells recover; minimal tissue damage, tissue regenerates with little to no scarring.
• Regeneration: Damaged tissue replaced with same type of cells; occurs in tissue where mitosis can occur.
• Replacement: Increased amount of missing tissue; functional tissue replaced by scar tissue; loss of function.
• Healing by primary (first) intention: Margins are well approximated and easily closed with sutures/staples/glue; minimal tissue loss; minimal scar tissue.
• Healing by secondary (second) intention: Distant edges, difficult to close; fibrin, collagen and scar tissue to close; includes pressure injuries.
• Healing by third intention: Deep, open wound is left open to resolve infection or contamination; once resolved, the wound is sutured.

Impairment of Healing

• Age.
• Infection.
• Decreased circulation and hemoglobin (less O_2 and nutrients available to tissue).
• Nutritional deficiencies (protein, Vitamin C, Vitamin A, Vitamin D, Zinc).
• Dehydration, edema.
• Comorbidities/chronic disease (Diabetes, liver, heart, renal diseases).
• Medications (glucocorticoids- block inflammatory response and healing).

"RICE" Therapy for Injuries

• Rest.
• Ice.
• Compression.
• Elevation.
• Other Therapies:
  • Elevation of inflamed limb.
  • Mild-to-moderate exercise.
  • Physiotherapy.
  • Occupational therapy.
  • Adequate nutrition and hydration.

Skin Integrity and Pressure Injuries

• Risk factors for altered tissue integrity, including pressure injury development:
  • Limited sensory perception.
  • Limited mobility.
  • Fecal or urinary incontinence and other prolonged moisture from wounds or drains.
  • Shear, friction.
  • Poor circulation, low hemoglobin, vascular disease, DM, Cancer, Tobacco use.
  • Poor nutrition, high blood sugar, dehydration.
  • Fragile skin, loss of sub Q tissue.
• Other risks for altered tissue integrity:
  • Abrasions, lacerations, burns, contusions.
  • Infection.
  • Environmental hazards: radiation, pollutants, temperature changes.

Pressure Injuries/Uclers

• Also called: pressure sore, decubitus ulcer, or bed sore.
• Pathogenesis:
  • Pressure.
  • Shear.
  • Friction.
  • Moisture.
• High risk areas: shoulders, tailbone, elbows, heels.

Classification of Pressure Injuries

• Only Pressure injuries are staged. The stage doesn’t change as the injury heals
• Stage I: Intact skin with non-blanchable redness.
• Stage II: Partial-thickness skin loss involving epidermis, dermis, or both.
• Stage III: Full-thickness tissue loss with visible fat (adipose).
• Stage IV: Full-thickness tissue loss with exposed bone, muscle, or tendon.
• Types of Necrotic Tissue:
  • Slough (moist):
    • Dead skin tissue, prevents healing
    • Yelow or white, stringy, clumps, slimy
  • Eschar (dry):
    • Necrotic tissue
    • Black, brown, tan, thick and leathery, fully adheres to wound
• Granulation Tissue:
  • Red, bumpy, moist tissue “berry like”.
  • Composed of new blood vessels, indicates a progression towards healing.
• Tissues:
  • Epidermis(1), Dermis(2), Adipose(3), Muscle/Tendon/Ligament(4), Bone(4)
• Visual Descriptions of Stages
  • Stage 1: Intact skin, non-blanchable erythema (redness)
  • Stage 2: Shallow open ulcer, pink/red wound bed, intact or ruptured serum filled blister
  • Stage 3: SubQ tissue visible (adipose), granulation tissue, slough or eschar, tunneling or undermining may be present
  • Stage 4: Visible fascia, muscle, tendon, ligament, cartilage, bone Slough, eschar
  • Unstageable: Wound base obscured
  • Suspected Deep Tissue Injury: Non-blanchable, deep red, maroon, purple Over a bony prominence

Prevention for Those at Risk for Pressure Injury and/or Poor Healing

• Pressure redistribution devices.
• Padding and repositioning medical devices.
• Routine turning and positioning *every 2 to 4 hours- limit sitting to 2 hours or less.
• Reduce shear and friction.
• Routine skin care and assessment.
• Manage moisture.
• Nutrition/glycemic control.
• Smoking cessation.
  • Never Massage an Injury.

Infection

• Nosocomial Infections: Occur in health care facilities also called healthcare-associated infections (HAIs).
  • Hospitals, nursing homes, physician’s offices, dental offices.
  • 10% to 15% of patients acquire an infection in the hospital because of:
    • Many microbes present.
    • Patients with infectious disease (pneumonia, C. diff, MRSA).
    • Shared environment.
    • Treatment that may cause weakened immune system.
    • Many health care workers and fomites (stethoscopes, blood pressure cuffs) act as reservoirs.
    • Other sources of infections: Foley catheters, IV tubing, ventilators , wounds.

Factors That Decrease Resistance to Infections

• Age (infants and older adults).
• Pregnancy.
• Genetic susceptibility.
• Immunodeficiency.
• Malnutrition.
• Chronic disease.
• Severe physical or emotional stress.
• Inflammation or trauma.
• Impaired inflammatory responses.

Physiology of Infection

• Incubation period: Time between entry of organism into the body and appearance of clinical signs of disease; varies considerably with different organisms.
• Prodromal period: Fatigue, loss of appetite (anorexia), headache; nonspecific—“coming down with something”; more evident in some infections than others.
• Acute period: Infectious disease develops fully.
• Convalescent period: Recovery.

Skin Disorders

• Rashes are a series of skin lesions. The physical appearance of the lesion is necessary to make a diagnosis.
• Skin lesions may be caused by:
  • Systemic disorders
    • Liver disease
    • Systemic infections
    • Chickenpox (varicella)
    • Autoimmune disorders (Lupus)
    • Allergies to ingested food or drugs
  • Localized factors
    • Include exposure to toxins, chemicals
  • Stress response

Skin Lesions

• What to know?
  • Types of lesions
  • Location
  • Length of time lesion has been present
  • Changes occurring over time
  • Physical appearance
    • Color
    • Elevation
    • Texture
    • Type of exudate (if present)
    • Presence of pain or pruritus (itching)
• Common Skin Lesions Overview:
  • Macule: Small, flat.
  • Papule: Elevated, palpable, small.
  • Nodule: Elevated, palpable, varies in size.
  • Pustule: Elevated, erythematous, purulent exudate, defined margin.
  • Vesicle: Elevated, clear fluid (blister).
  • Plaque: Large, slightly elevated, flat surface, scale.
  • Crust: Dry, rough surface or dried exudate/blood.
  • Lichenification: Thick, dry, rough, leather-like surface.
  • Keloid: Raised, irregular, excessive collagen from scar tissue.
  • Fissure: Small, deep, linear crack or tear.
  • Ulcer: Cavity with tissue loss, weeping/bleeding.
  • Erosion: Shallow, moist cavity.
  • Comedone: Mass of sebum, keratin, debris blocking hair follicle.

Pruritis

• Irritating sensation that creates an urge to scratch; itchy
• Associated with
  • Allergic responses
  • Chemical irritation caused by insect bites
  • Infestations by parasites (e.g., scabies)
• Mechanism not totally understood, Release of histamine in a hypersensitivity response causes marked pruritus, Infection may result from breaking the skin barrier, Caused by scratching

Skin Rashes Causes

• Bacterial Infections:
  • Pustule- Painful lesions on specific areas
• Viral Infections (Shingles):
  • Vesicles- painful, thin-walled lesions filled with clear fluid over the entire body
• Fungal Infections:
  • Macular/Papular- painful lesions in warm moist areas without discharge
• Allergic Dermatitis (Chemical exposure, food allergy):
  • Macular/Papular- itchy rash that can be local or systemic

Skin Disorders

• Contact Dermatitis:
  • Red localized rash, with severe itching, bumps, swelling, burning, tenderness
  • Caused by direct contact with chemical material that damages the skin
• Atopic Dermatitis (Eczema):
  • Inherited tendency to develop, Chronic Allergic response to irritants, Redness, swelling and scaling with areas of dry and itchy skin, Serous exudate
• Allergic Contact Dermatitis:
  • Itchy or painful rash covering a large area due to immune response, Reaction to the skin touching an allergen (poison ivy, nickle, latex)
• Hives (Urticaria):
  • Type I Hypersensitivity, Ingestion of substance: shellfish, fruit, drugs, Physical factors: pressure, heat, cold, Other: stress, illness, infections, Hard raised, red lesions, Itchy, Scattered over body
• Shingles:
  • Painful blisters and crusted areas over a dermatome (single spinal nerve root), burning and itching sensation, caused by the reactivation of the varicella-zoster virus, PAIN, itching, fever

Immunity

• Specific Immune System: Production of specific antibodies against foreign substances.
  • 3rd line of defense, often simultaneous to inflammation
  • Lymphoid system: Lymph nodes, spleen, tonsils, thymus
  • Immune Cells: Lymphocytes and Macrophages
  • Tissues: development of immune cells
    • Bone marrow -origin of all immune cells
    • Thymus -maturation of T lymphocytes
• Antigen: any substance that triggers an immune response
  • Can include toxins, chemicals, bacteria, viruses, body tissues and cells, including cancer
    • Self: The immune system recognizes an antigen that labels a cell as “self” causing it to ignore that cell
    • Non-self: The immune system recognizes non-self antigens on a substance and responds
• Types of immunity:
  • Humoral immunity: antibodies are produced
  • Cell mediated immunity: lymphocytes are programmed to attack non-self cells to protect the body
• Specific Immune Response Cells:
  • Macrophages:
    • Present throughout the body, Develop from monocytes, Initiation of the immune response, Engulf foreign material, Display antigens of foreign material to lymphocytes, Secrete chemicals (monokines, interleukens)
  • T Lymphocytes:
    • Develop from bone marrow stem cells, Differentiate further in the thymus, Cell mediated immunity, Cytotoxic T killer cells, Helper T cells, Memory T cells
  • B Lymphocytes:
    • Develop from bone marrow stem cells, Proceed to spleen and lymphoid tissue, Humoral immunity, Plasma cells, Produce antibodies, B Memory Cells, Quickly forms clone of plasma cells
• Acquired Immunity: Antigen-Specific Responses
  • Antigen binds to antibody - Antigen binding site
  • Functions of antibodies - Bacterial toxins
    • Activates complement
    • Triggers mast cell degranulation
    • NK cell or eosinophil
    • Activates antibody-dependent cellular activity
    • Causes antigen clumping and inactivation of bacterial toxins
    • Acts as opsonins Enhanced phagocytosis
    • Activates B lymphocytes - Secrete antibodies
    • Memory Plasma
    • Antibody Proteins are produced to bind with a specific antigen on B Lymphocyte Hold and mark for destruction
• Antibodies:
  • IgG – most common, fight infection, passive immunity for fetus
  • IgM – first responder, incompatibility reaction to blood
  • IgA – in secretions: tears and saliva, protection for newborns through colostrum
  • IgE – allergic response, release histamine and trigger inflammation
  • IgD – attaches to and activate B-Cells
• Complement System: NON-SPECIFIC
  • A group of proteins in blood plasma that interact with foreign antigens
  • Chemical mediators include: kinins, histamine, prostaglandins and chemotactic factors
  • Chemicals are activated when the proteins of the complement system and a foreign antigen combine forming an antigen-complement complex
  • This enhances B cell activation and differentiation, phagocytosis, cell lysis, inflammation,removal of dead cells
• Types of Immunity:
  • Natural – species- specific (some infections can’t jump species)
  • Innate – gene-specific, related to ethnicity, born with it, ex: enzymes, skin
• Acquired
  • Passive – does not require synthesis of antibodies
    • Natural – from mom to fetus through placenta or breast milk
    • Artificial – antibodies injected, antiserum (rabies, tetanus, anthrax) or anti- venom
  • Active – requires body to synthesize antibodies after exposure to antigen
    • Natural – natural exposure to antigen, such as an exposure to a pathogen (chickenpox)
    • Artificial – antigen purposefully introduced to the body, vaccination (measles vaccine)

Hypersensitivity Reactions

• Type I – Allergic reactions
  • Common and increasing, Caused by allergen, IgE, triggers inflammation, Can lead to anaphylaxis: life-threatening severe systemic allergic rxn, Hay fever, food allergies, atopic dermatitis or eczema, asthma
  • Emergency treatment: Epinephrine, Glucocorticoids, Antihistamines, Oxygen, Stabilize BP
• Type II – Cytotoxic
  • Antigens present on a cell membrane are destroyed by antibodies, IgG and IgM, Incompatible blood transfusions, Rh incompatability
• Type III – Immune Complex
  • Antigen and antibody combine to form complex, Activates inflammation and complex lodges in tissue, May cause chronic inflammation, Glomerulonephritis, Rheumatoid arthritis, Lupus
• Type IV – Cell-Mediated or delayed
  • Delayed response, triggers inflammation and T-Cells, May take 24 hours, TB Test, poison ivy, latex, organ transplant rejection

Immune System Errors

• Autoimmune Disorders
  • Cannot distinguish self from non- self, Autoantibodies formed against self, Inflammation, Lupus, Hashimoto thyroiditis, Scleroderma
• Immunodeficiency
  • Compromised immune system, Increased risk of infection and cancer
    • AIDS (Acquired Immunodeficiency Syndrome): caused by HIV (Human Immunodeficiency Virus)
      • Virus destroys helper T cells (CD4 cells) resulting in loss of immune response, Increased susceptibility to secondary infections and cancer (Kaposi sarcoma, non-Hodgkin lymphoma), Transmitted by blood, semen, vaginal fluid, breast milk