Inflammation & Tissue Integrity

Chemotaxis

Movement of cells or organisms in response to chemicals, whereby the cells are attracted (positive chemotaxis) or repelled (negative chemotaxis) by substances exhibiting chemical properties

• Stimulated by:

  • Bacteria or viral exotoxins

  • Degenerative by-products of inflammation

  • Products of complement system activation

  • Reactive products of plasma clotting

Pro inflammatory Hormones

Chemicals that stimulate a complex process involving more than a dozen different chemicals

• They increase blood flow to the area of injury, increase vascular permeability, activate components of an immune response, attract leukocytes to the area of injury, promote angiogenesis, stimulate connective tissue growth, and cause fever

• They are secreted by injured tissues and local granulocytes and tissue masts

Vascular permeability

Leakage of capillaries

• As part of the vascular response in the first stage of inflammation, capillary permeability causes swelling, edema, and pain

• Proinflammatory hormones increase vascular permeability

Angiogenesis

Growth of blood vessels and is promoted by proinflammatory hormones

• It is triggered by white blood cells to replace lost or damaged tissue

Phagocytosis

Begins in the cellular response stage, or Stage Two, of inflammation, specifically 12 hours after an injury when neutrophilia occurs

• During this stage, neutrophils perform phagocytosis, but then die

Hyperemia

An increase in blood flow that delivers nutrients such as oxygen and glucose to injured tissue

• It is also characterized by redness and warmth

• Hyperemia occurs during the vascular response stage, or Stage One, of inflammation, when small veins constrict and arterioles dilate

Neutrophilia

Occurs during the cellular response stage, or Stage Two, of inflammation, specifically 12 hours after an injury

• During this stage, eosinophils, basophils, and tissue mast cells promote a continuous inflammatory response

Exudate

Forms during the cellular response stage of inflammation and is made of dead white blood cells, necrotic tissue, and leaked cell fluid. Exudate can be described as:

• Serous: clear, watery plasma

• Serosanguineous: semi-clear and pink, consisting of a mixture of red blood cells and serous fluid

• Sanguineous: bright red, indicating active bleeding

• Purulent: thick, yellow, green, tan, or brown, which may indicate a possible infection

Arachidonic acid

Arachidonic acid is created when fatty acids in the membranes of injured cells are converted by the COX enzyme into substances such as histamine, leukotrienes, prostaglandins, serotonin, and kinins that promote more inflammation. NSAIDs can stop this cascade process. This process is called the arachidonic acid cascade and occurs during Stage Two: Cellular Response.

CRP

An inflammatory marker

• CRP is helpful in detecting an acute inflammatory picture

• You can investigate inflammation through blood tests such as CRP

Necrosis

A lethal injury that is an irreversible process that causes cell death

Types of necrosis include:

• Coagulative (MI)

• Liquefactive (abcess)

• Caseous (TB)

• Gangrene

ESR

(Erythrocyte sedimentation rate) is a blood test used to investigate inflammation

• ESR is noted in chronic inflammation

• You can investigate inflammation through blood tests such as ESR2. Normal ESR is <20mm/hr4

Serous exudate

Serous exudate is clear, watery plasma. It is expected with wound healing. Exudate forms during the cellular response stage of inflammation.

Purulent Exudate

Purulent exudate is thick, yellow, green, tan, or brown. Its presence may indicate a possible infection. Exudate in general forms during the cellular response stage of inflammation.

Hemorrhagic exudate

The sources do not directly define hemorrhagic exudate, but the characteristics of exudate are described. Exudate forms during the cellular response stage of inflammation. There are several types of exudate.

Hemorrhagic exudate is characterized as bright red, indicating active bleeding.

Leukocytosis

Leukocytosis is a systemic response clinical manifestation of inflammation. It is characterized by an increase in white blood cells. A complete blood count (CBC) can determine whether neutrophils are present.

Malaise

A systemic response and clinical manifestation of inflammation. Systemic clinical manifestations such as malaise are vaguer and more difficult to link together.

RICE

RICE refers to Rest, Ice, Compression, and Elevation, and is a non-pharmacological intervention used for sprains and strains.

• Rest is used to prevent further reinjury and trigger inflammation.

• Ice should be applied for 10 minutes at a time every 2-3 hours.

• Compression is used to reduce swelling. A wrap can be used to contain edema and shrink it over time.

• Elevation involves elevating the injury above the level of the heart to minimize swelling and promote circulation.

RICE is typically implemented in the first 24-48 hours after an injury.

Antipyretics

When treating a fever acetaminophen is the drug of choice.

Adrenal crisis

Results from sudden withdrawal of corticosteroid medications

• The adrenal glands are controlled by the release of ACTH from the pituitary gland through negative feedback

• Exogenous cortisol suppresses pituitary release of ACTH and suppresses the production of natural cortisol by the adrenal glands

• Adrenal crisis symptoms include hypotension, flu symptoms, seizures, and shock

Exogenous cortisol

Suppresses the pituitary gland's release of ACTH, which in turn suppresses the production of natural cortisol by the adrenal glands. This process is relevant in the context of adrenal crisis, which can result from the sudden withdrawal of corticosteroid medications.

Sublethal injury

Injuries in which the changes are potentially reversible if the harmful stimulus is removed. They are common and part of normal physiological processes but may also result in pathological changes.

Examples of sublethal injuries include:

• Exposure to sunlight stimulating melanin, causing tanning of the skin

• Lack of muscular activity leading to atrophy and decreased tone

• Expansion of cell size in the uterus during pregnancy, which retracts postpartum

Lethal Injury

Irreversible process that causes cell death.

• Types of cell death include apoptosis and necrosis.

• Examples of situations that can result in lethal injuries include severe burns, which may result in wet gangrene

Apoptosis

Programmed cell death that is normal for homeostasis, like in skin or gut epithelium

• It is a type of lethal injury, which is an irreversible process that causes cell death

Gangrene

Type of necrosis, or tissue death from various causes. There are two main types of gangrene:

• Dry gangrene: Involves degenerative changes that occur with certain chronic diseases like diabetes or atherosclerosis, when blood supply is gradually reduced.

• Wet gangrene: Involves the sudden, rapid elimination of blood flow (severe burn or crush injury). There is extensive tissue liquefaction making the affected area soft and malodorous. Wet gangrene may result from a lethal injury.

Primary Intention

Wound healing in which the edges are approximated and clean, such as with surgical incisions

Secondary Intention

Secondary intention describes a type of wound healing that occurs when there is a large gap and irregular edges, such as with a pressure injury

Tertiary Intention

A type of wound healing that is delayed due to infection. In tertiary intention, the wound is left open initially. An example of tertiary intention wound healing is a dog bite

Partial Thickness

A partial thickness wound affects the epidermis and goes into the dermis.

Characteristics of stage 2 pressure injuries

Full Thickness

A full thickness wound affects the deepest layer of tissue including the subcutaneous tissue, fascia, muscle, tendon, and/or bone

Full thickness wounds include:

• Stage 3 pressure injuries where adipose tissue is visible and granulation tissue, slough, or eschar may be present. Undermining and tunneling may occur, but fascia, muscle, tendon, ligament, cartilage, and bone are not exposed

• Stage 4 pressure injuries where fascia, muscle, tendon, ligament, cartilage, or bone are exposed. Slough or eschar may be visible, and undermining or tunneling may occur

• Unstageable pressure injuries involve full thickness wounds where the extent of the damage cannot be confirmed because it is obscured by slough or eschar. If slough or eschar is removed, a stage 3 or 4 pressure injury is revealed

Pressure Injury

A localized injury to the skin or underlying soft tissue, usually over a bony prominence

• The most common sites for development are the sacrum, ischium, trochanter, coccyx, heels, and malleolus

Primary Lesion

Develops on unaltered skin

Examples of primary lesions include:

• Macule: mainly a color change and flat, like a freckle

• Papule: solid and elevated, like a mole

• Wheal: superficial, raised, erythema, and edematous, like an allergic reaction/urticaria

• Vesicle: cavity with clear fluid, like a blister

• Pustule: cavity with pus

Secondary Lesion

A secondary lesion develops when a lesion changes over time from infection or scratching.

Examples of secondary lesions include:

• Crust: thickened dried out exudate

• Scale: compact flakes of skin

• Fissure: crack

• Erosion: scooped out but shallow

• Ulcer: deeper depression

• Excoriation: self-inflicted abrasion

• Scars

Slough

Wet, necrotic tissue that creates an environment for bacterial growth

• It can be present in full thickness wounds, including stage 3 and 4 pressure injuries

• Slough appears yellow in colour

Eschar

Thick, dry, necrotic tissue that is black, brown, or grey

• It may be present in full thickness wounds, including stage 3 and stage 4 pressure injuries

Sanguineous Exudate

Sanguineous exudate is bright red in colour, indicating active bleeding.

Dehiscence

A complication of impaired tissue integrity characterized by the separation and disruption of previously joined wound edges.

Evisceration

A complication of impaired tissue integrity where wound edges separate to the extent that intestines protrude through the wound

Fistula

A complication of impaired tissue integrity and is defined as an abnormal passage that forms between organs or a hollow organ and the skin

Braden Scale

The Braden Scale is a tool used for predicting pressure sore risk. It has six subscales: sensory perception, moisture, activity, mobility, nutrition, friction, and shear. A score less than 18/23 indicates risk. The Braden Scale is used upon admission and for periodic assessment to identify a patient’s risk for skin breakdown. Strategies based on the Braden Scale include minimizing or eliminating friction/shear (using sliding sheets), minimizing pressure by frequent repositioning/use of pressure-relieving devices (mattresses), managing moisture (continence control) and ensuring adequate nutrition and hydration.

NSAIDS

NSAIDs are “non-steroidal anti-inflammatory drugs”. NSAIDs are our first line of medications used to treat mild to moderate inflammation. By blocking the action of a COX enzyme, inflammation is reduced. As you learned in the pain lecture, NSAIDs come with risks.

Glucocorticoids

Glucocorticoids are also sometimes called corticosteroids. In contrast to NSAIDs, these compounds are “steroidal” in nature. They are normally present in the blood in low levels, and during periods of stress they are secreted in larger amounts. When they are given as a medication in high doses, they have very potent anti-inflammatory effects. Because of this, they are more useful for acute and severe inflammation. One of the most common glucocorticoids you will see in practice is prednisone

Inflammation

Body’s reaction to injury, irritation, or infection characterized by redness, swelling, warmth, &/or pain; caused by accumulation of immune cells & substances around the injury or infection

Protective process initiated to minimize or remove the pathologic agent or stimulus triggering inflammation & to promote healing

• Inflammation is always w/ infection but inflammation can also happen w/out infection

• Natural defence in our bodies that has a sequence of events that take place: Vascular response, Cellular response, & Repair & Replace

Pathophysiology Triggers

• Mechanical trauma

• Thermal, electrical or chemical injury

• Radiation damage

• Biological assault (infections)

Goal of Normal Inflammatory Response

• Restore normal function of cells

• Fibrous repair when cells can’t be restored

Normal Inflammatory Response: Physiologic Process

White blood cells & chemicals that serve to protect the body from invaders or cellular/tissue damage are involved

White Blood Cells

• Attracted to inflammation site when chemotaxis occurs

  • Segmented neutrophils

  • monocyte(spread throughout body; turns to macrophages) - immature (when infection occurs; matures quickly)

Stage One: Vascular Response

• Injured tissues & local granulocytes & tissue masts(causes alarms to ring) secrete proinflammatory hormones

  • Small veins constrict & arterioles dilate

    • Blood flow increases delivering nutreints (oxygen, glucose) to injured tissue (Hyperemia/Redness, Warmth, and Edema)

    • Capillary leak/permeability (Swelling/Edema and Pain) - plasma (will make pain worse)

  • Macrophages secret proinflammatory hormones

    • Matures WBCs quicker and promote neutrophil invasion

Stage Two: Cellular Response

• Granulocytes & Tissue Mast cells become activated

  • Neutrophils occurs 12hrs after injury: Phagocytosis begins

  • Eosinophils, Basophils & Tissue Mast cells promote continuous inflammatory response (Neutrophilia)

    • neutrophils did phagocytosis = dies

• Exudate forms: Dead WBCs, necrotic tissue, leaked cell fluid

• Macrophages increase & stimulate monocyte production

• Arachidonic acid cascade

  • Fatty acids in membranes of injured cells into arachidonic acid which is then converted (by COX enzyme) into substances (histamine, leukotrienes, prostaglandins, serotonin, kinins) that promote more inflammation

    • NSAIDs stop this cascade process

Stage Three: Tissue Repair & Replacement

All white blood cells involved start the replacement of lost/damaged tissues by stimulating healthy cells to divide

• White blood cells trigger blood vessel growth (angiogenesis) and scar tissue formation for those cells that cannot divide

• Function of these cells are lost

Regeneration: Replacement of lost cells and tissues with cells of the same type

• Skin, mucous membranes of GI/urinary/reproductive

• Liver/pancreas/kidney/bone cells

• Neurons do not regenerate – permanent loss

Repair: Result of lost cells being replaced by connective tissue – more common type of healing (scar formation)

• Occurs simultaneously with stage one/two

  • Chronic inflammatory stage

Acute Inflammation Duration

• Duration: Stage 1 & 2: 3-5 days, stage 3: 2 to 3 weeks

• Usually leaves no lasting damage (inflammation itself, not injury)

Neutrophils

Predominant cell type at the site of inflammation

C Reactive Protein (CRP)

• an inflammatory marker

  • No blood work done; know what type of pain it is

Chronic Inflammation

• Prolonged inflammation - lasts for weeks, months, or even years

• Lymphocytes & Macrophages (important):

  • Release tissue thromboplastin----facilitates hemostasis, promotes fibroblasts

  • Removes necrotic tissue and pathogens (debridement)

  • Continuous release of pro-inflammatory cells

• Thinking & scarring of connective tissue

• May also be “subclinical”

  • No overt symptoms – more systemic manifestations

  • Investigate through blood tests: CRP (can tell you acute on chronic picture) and ESR (erythrocyte sedimentation rate)

• May need a WBC scan to identify areas of inflammation

Assessment

• Local Response vs Systemic Response

  • Extensiveness

  • Location

  • Dependent on patient’s immune response

  • Dependent on acute vs chronic process

    • b/c of inflammatory hormones

Local Response

• Swelling

• Pain

• Warmth

• Redness

• Exudate or impaired function

  • Serous(plasma)/fibrinous/prulent(infectious, yellow)/hemorrhagic

Systemic Response

• Leukocytosis

• Fever

• Malaise

• Nausea, anorexia, loss of appetite

• Muscle catabolism (if long standing)

Additional Findings (Systemic/Chronic)

• Diagnostics

  • Imaging

  • CT/MRI/Endoscopy

• Blood

  • CRP

  • ESR

  • WBC (to check whether neutrophils are present)

Management

• Collaborative Interventions

  • Goals: Mediate intermediate process & promote healing & repair

• Treat underlying cause

  • Infection-eliminate cause

  • Hypersensitivity reponse-manage inflammation & manage the pathologic issue (e.g. DM, RA, MS)

• Sprain/Strain: RICE & NSAIDS

• Chronic: monitor to prevent further tissue damage, treat cause, support ongoing tissue functio, medications

  • (Eg. Type 1 Diabetes, provide insulin)

Non pharmacological Interventions

RICE: always do nonpharm. interventions 1st!

Rest

Ice

Compression (wrap; contain edema → shrink overtime)

Elevation (circulation)

• First 24-48hrs after injury

  • Rest to prevent further reinjury & trigger inflammation

  • Ice for 10 mins, every 2-3 hours

  • Compression to reduce swelling

  • Elevate above level of heart to minimize swelling

Reducing Inflammation

• Steroidal Agents:

  • Glucocorticoids: Prednisone

• Nonsteroidal Ati-Inflammatory Drugs (NSAIDS)

  • Ibuprofen (do not give w/ food; in drug card: GI information in important)

Managing Fever: Pharmacological Intervention

• Antipyretics

  • Acetaminophen

  • Aspirin (don’t use it for fevers/headaches = cause you to bleed easier)

  • NSAIDS

Pain Relief

• Analgesics

  • Acetaminophen

  • Aspirin

  • NSAIDS

  • OPIOIDS (if pain is severe)

Reducing Inflammation: Mechanism of Action of drug therapy

Not stop Cox 1/2 → make inflammatory process much worse; how?

chronic - may give steroids (stop immune system from working)

Difference in the MOA of prednisone vs nsaids

The sources indicate that the mechanisms of action (MOA) of prednisone and NSAIDs differ in the following ways:

NSAIDs (e.g., Ibuprofen)

• Inhibit prostaglandin synthesis by blocking cyclooxygenase (COX) 1 and 2, which decreases inflammation.

Prednisone (a glucocorticoid)

• Inhibits the synthesis of prostaglandins by the COX II pathway.

• Suppresses some phagocytes and lymphocytes, leading to immunosuppression.

• Suppresses histamine release.

• Decreases inflammation through suppressing immune responses by inhibiting macrophage accumulation and reducing capillary permeability.

In summary, NSAIDs block COX 1 and 2 to inhibit prostaglandin synthesis, while Prednisone inhibits prostaglandin synthesis through the COX II pathway, suppresses the immune system, and suppresses histamine release.

System Corticosteroids: Glucocorticoids

Have endogenous forms but when given through exogenous; will impact

• Nearly produced by adrenal glands

• Suppress histamine release

  • Inhibits synthesis of prostaglandins by COX II pathway

  • Suppress some phagocytes, & lymphocytes: Immunosuppression

• Dosing is critical

  • Long term - low dose ( Addison’s patients will require this for rest of their lives)

  • Short-term — higher dose

    • Ex: chronic inflammatory situation; lower doses in a longer period of time & vice versa

• Titration is CRITICAL to preventing serious side effects

— dont abruptly stop taking it (until safe enough level) + hard on stomach (mucosal lining will get eaten away) + “Roid Rage” + Dont give when (…) b/c we told our bodies immune system to turn off + ISDE EFFECTS ARE VERY IMPORTANT

Sudden Withdrawal & Adrenal Crises

• Adrenal glands are controlled by release of ACTH from pituitary gland through negative feedback

• Negative feedback:

  • Exogenous cortisol suppresses pituitary release of ACTH and suppresses production of natural cortisol by adrenal glands

• Adrenal Crisis results from sudden withdrawal:

  • Hypotension, flu symptoms, seizures, shock

• Theraphy is kept short-term (less than 10 days)

• If long-term, may give EOD; requires dose to be tapered as its discontinued so adrenals resume production

Nursing Role: Inflammation

Assess & treat local & systemic manifestations of inflammation

Tissue Integrity

Muscle – Neural – Connective – Epithelial

State of structurally intact and physiologically functioning epithelial tissues, such as the integument (including the skin and subcutaneous tissue) and mucous membranes

Epidermis - Dermis - Subcutaneous Layer Function

• Protection

• Perception

• Temperature regulation

• Identification

• Communication

• Wound Repair

• Absorption & Excretion

• Production of Vitamin D

3 Ways Wound Healing Occurs

• Primary: edges approximated, clean: surgical incisions

• Secondary: large gap and irregular edges: pressure injury

• Tertiary: delayed healing from infection, left open initially: dog bite

  • Changes are potentially reversible if harmful stimulus is removed

  • Sublethal are common and part of normal physiological processes, they may also results in pathological changes. Exposure to sunlight stimulates mealin which causing tanning of the skin. Lack of muscular activity can lead to atropy and decreased tone.

• Adaptive and Maladaptive Processes

Types of Cell Death

Apoptosis, Necrosis

Apoptosis

Programmed cell death, normal, homeostasis like our skin or gut epithelium

Necrosis

Tissue death from various causes

Types of necrosis

Coagulative (MI), Liquefactive (abscess), Caseous (TB), Gangrene (Dry & wet)

Coagulative Necrosis Example

Myocardial infarction (MI)

Liquefactive Necrosis Example

• (abscess)

  • Ex: Bacterial infection = no cell death occurring

Caseous Necrosis Example

Tuberculosis (TB)

Gangrene Ecrosis Examples

• Dry form (People w/ diabetes)

  • Dry Gangrene: degenerative changes that occur with certain chronic diseases like diabetes or atherosclerosis, when blood supply is gradually reduced

  • Wet Gangrene: sudden rapid elimination of blood flow (severe burn or crush injury). Extensive tissue liquefaction making the affected area soft and malodourous (intense smell)

Hypertrophy

Expansion of size in cells which results in increased tissue mass without cell division (in disease process; muscle is working too hard → will get larger = will make ventricles smaller)

Hyperplasia

Multiplication of cells as a result of increased cellular division

Atrophy

Decrease in size of a tissue or organ as a result of a reduction in number or seize of cells usually caused by disease, lack of blood supply, natural aging, inactivity or nutritional deficiency

Metaplasia

Transformation of one cell type into another due to change in physiological condition or external irritant. (could be harmful type of process; one of the worse forms: lung cells become something else)

Dysplasia

Abnormal differentiation of dividing cells that results in changes in size shape an appearance. Precursor of malignancy

Anaplasia

Cell differentiation to a more immature or embryonic form. Malignant tumors.

Trauma/Injury

Intentional or unintentional (superficial abrasion or scrape to deep wound penetrating the skin and SQ layers with extension to muscle, organs, bone) (surgical incision is intentional

Loss of Perfusion

Prolonged can lead to tissue necrosis (chronic poor perfusion leads to ulcerations, necrosis, loss of digits) (short term disruption caused by pressure leads to pressure injuries)

Immunologic Reaction

Range from redness/rash/hives to Steven Johnson Syndrome

Infections & infestations

Bacteria/fungi/virus

Thermal or Radiation Injury

Sunburn to burns, radiation therapy, frostbite

Lesions

Benign to invasive

Factors Delaying Wound Healing

• Nutrition

• Inadequate blood supply

• Smoking

• Corticosteroids

• Infection

• Anemia

• Advanced age

• Obesity

• Diabetes Mellitus

• Poor general health

• Mechanical friction on wound

• Cold temp

• Excessive moisture

Classified by Cause

• Surgical or nonsurgical, underlying pathology (vascular, pressure, diabetes related), duration (acute or chronic), level of contamination, or type of tissue affected (superficial, partial thickness, or full thickness)

  • Superficial: Epidermis only

  • Partial: Into dermis

  • Full: Deepest layer of tissue (subcutaneous tissue, fascia/muscle/tendon/bone)

    • Stage 3 Sacral Pressure Injury

      • Diabetic Foot Ulcer

      • Surgical-Abdominal Incision

Lesions: Traumatic or pathological changes in normal structures

• Common Shapes/Configurations

  • Zosteriform (herpes zoster)

  • Grouped (dermatitis)

  • Confluent (hives)

• Primary & Secondary

  • When lesion develops on unaltered skin, it is primary. If lesion changes over time from infection/scratching, it is secondary

Primary Lesion

• Macule (freckle) – mainly color change/ flat

• Papule (mole) – solid, elevated

• Wheal (allergic reaction) – superficial, raised, erythema, edematous

• Urticaria

• Vesicle (blister, cavity with clear fluid)

• Pustule (cavity with pus)

Secondary Lesions

• Debris on skin

  • Crust (thickened dried out exudate)

  • Scale (compact, flakes of skin)

• Break in continuity of surface

  • Fissure (crack)

  • Erosion (scooped out but shallow)

  • Ulcer (deeper depression)

  • Excoriation (self inflicted abrasion)

• Scars

Wound Bed Colour: Red

• Red (Granulation Tissue)

  • Superficial or deep that is clean, red or pink

  • Example: Skin tears, pressure injuries, surgical wounds

  • Approach: Gentle cleansing and protection

Wound Bed Colour: Yellow (Slough)

• Wet, necrotic tissue creating an environment for bacterial growth

  • Firm when taking it off

• Approach: Absorption of excessive drainage and removal of nonviable tissue

Wound Bed Colour: Black (Eschar)

• Thick, dry, necrotic tissue that is black, brown, or grey

• Example: Third degree burns, gangrenous ulcers

• Risk of infection increases

• Approach: Removal of nonviable eschar (debridement)

Pressure Injuries

• Localized injury to the skin or underlying soft tissue, usually over a bony prominence

• Most common sites for development are sacrum, ischium, trochanter, coccyx, heels, malleolus