THE INFLAMMATORY PROCESS

NCM 104 – LECTURE

CLASS 2015

Inflammation

• What is Inflammation• A vascular and cellular response to trauma.

Its purpose is to initiate the healing of the injured tissue

• The body’s attempt to dispose of micro-organisms, foreign material and dying tissues so that tissue repair can occur

• An inflammatory response may result from external or internal factors (infection)

• Protects to the body by localizing and removing the injuring agent

Signs of Swelling

• Redness (Rubor)• Swelling (Tumor)• Pain (Bolar)• Warmth (Calor)• Loss ROM

Signs of Inflammation (Cardinal Signs)

• Redness (Rubor):• Caused by blood vessel dilation (the arterioles)• Chemical mediators promote the vessel dilation

(contained in the capillary walls or endothelium resulting in immediate response)• Histamine• Seritonin• Bradykinins• Prostaglandins• Note: a 1x increase in arteriole diameter yields a

4x increase in blood flow

Signs of Inflammation Cont.• Swelling (tumor)

• Edema fluid varies with the stage of inflammation• initially vessel permeability is only

slightly altered and no cells or protein escapes and the fluid is mainly water and dissolved electrolytes (transudate): like synovial fluid

• As capillary permeability increases and plasma proteins escape the extravascular fluid becomes cloudy and more viscous. This is called exudate (contains a large amount of leukocytes (called pus)

Causes of Edema/Swelling-• bleeding from torn vessels• cell death due to anoxia, allows fluid leakage

(permeability increases)• increased proteins raise extracellular osmotic

pressure, drawing fluids from the capillaries• Chemicals alter cell permeability to proteins

and fluid• Gravity may increase swelling (Capillary

filtration pressures)

Edema/Swelling

• To cease hemorrhage/swelling/edema• Must reverse the condition

• pressure gradient• vessel repair

Signs of Inflammation Cont.

• Pain (bolar)• Results from irritation of nerve ending

by physical or chemical factors• Physical trauma may irritate pain

receptors• Chemical mediators release when cell

damage occurs sensitize pain receptors• Trauma may result in cell anoxia

because of interference with blood flow due to capillary damage

Signs of Inflammation Cont.

• Warmth (calor)• The result of chemical activity and

increased blood flow in the injured area.• Loss of Function

• May occur due to pain causing reflex guarding or muscle spasm • spasm decreases metabolic activity

and constricts blood flow which causes more pain due to ischemia; thus the pain/spasm cycle

Phases of the Inflammatory Process

• Phase I: Acute Phase ( 2 subphases)• Early (Acute): inflammatory response: lasts 2-4 days • Late (Sub-Acute): continue inflammatory phase

which is usually complete in 2 weeks• Phase 2: Tissue Formation (Proliferation)

• Tissue rebuilding approximately 2-3 weeks• This does not include chronic inflammation

• Phase 3: Remodeling Phase• Adapt to original tissue • Continues for up to 1 year post injury

Phase I: The Inflammatory Process

• Early Phase• Insult occurs - may be internal (infection) or external

(trauma)• Vasoconstriction to decrease blood flow (first 10

minutes)• Vasodilatation

• Late Phase• Tissue Repair • Regeneration

Phase I -Early Phase: Acute Inflammation

C h em ica l M ed ia to rs R e leased (C h em otaxis )C u ases V asod ila tion

In c reases B lood , P lasm a, P ro tien s , P h ag ocytic m ate ria l

P ro tien s a re In c reas ed a t In ju ry S iteIn c rease in p ro tien s cau ses osm otic re la tion sh ip w ith p lasm a

H 2 O flow s from h ig h er p ro tien s con ten t (in ju ry)to in te rs t ia l flu id cau s in g ed em a/sw e llin g

S w e llin g /ed em a a re d ec reased b y lym p h atic sys tem

In ju ryO n se t

Inflammatory Phases

0%10%20%30%40%50%60%70%80%90%

100%

Day 1 Day 2 Day 3 Day10 Day 30 Day 90

Phase IIIPhase IIPhase I LatePhase I Early

Chart Designates Percent of phase over time

Phase I: Early Phase Inflammation - Vasodilatation

• Chemical mediators are released:• histamine, bradykinis, serotonin, prostaglandin's -

increase vascular permeability released from mast cells and blood platelets into traumatized tissue.

• As fluid filtrates through “gaps in the extravascular spaces this is called exudation.

Phase I- Early Phase: Vasodilatation Cont.

• The accumulation of excess fluid is called edema (Swelling)

• Vascular permeability due to action of the histamine is short-lived, lasting less than 1 hour

Phase I: Early Phase Inflam. - Lymphatic channels are blocked

• Local lymphatic channels are blocked by fibrin plugs formed during coagulation. Obstruction of the local lymphatic channels prevents drainage of fluid from the injured site, thus localizing the inflammatory reaction.

Phase I- Late Phase: Phagocytosis

• Body’s cellular defense to remove toxic material via lymphatic system

• Phagocytosis: a process when leukocytes capture and digest foreign matter and dead tissue• 1st line of defense: neutrophiles (in most

abundance from 1-3 days) - phagocytic activity reaches maximum effectiveness within 7-12 days

Phase I- Late Phase: Phagocytosis Cont.

• 2nd line of defense: monocytes (which convert into large cells called macrophages) and lymphoctes consume large amounts of bacteria and cellular debris. Monocytes are critical in the initiation of tissue repair because the attract fibroblasts

Macrophage

Bacteria

Phase I- Late Phase Phagocytosis Cont.

• Pus is the end result - it contains leukocytes, dead tissue and phagogenic material• Prolonged puss accumulation can

prevent fibroplasia which begins the wound healing

• Fibroblasts are connective tissue responsible for collagen synthesis• Ligaments, joint capsule, tendon

• Osteoblasts: responsible for bone synthesis

Fibroblast Macrophages

Phase I: Early Phase Inflammation - Margination

• When trauma occurs the endothelial wall is disrupted exposing collagen fibers creating a “stickiness”

• WBC’s concentrate in the injury site to rid the body of foreign substances and dead (necrotic) tissue

Phase I- Late Phase: Margination Cont.

• As circulation slows, leukocytes migrate and adhere to the walls of post-capillary veinuels (for approx 1 hour)

• The leukocytes pass through the walls of the vessels (diapedesis) and travel to the site of injury (Chemotaxis)

Phase I: Late Phase Blood Clotting

• Ruptured vessels release Enzyme (Factor X)• Factor X reacts with prothrombin (free floating

in blood)• Thrombin then stimulates fibrogen into its

individual form fibrin• Fibrin grouped together to form “lattice”

around injured area• Fibrin lattice contracts to remove plasma and

compress platelets forming a “patch”

Phase I: Late Phase Blood Clotting

Factor X

Prothrombin

Thrombin

Fibrogen and Thrombin Meet

Fibrin Monomer

Fibrin Mesh

Fibrin Forms Seal

Phase II: Regeneration:

• The replacement of destroyed cells by reproducing healthy cells adjacent to the wound (humans capacity to regenerate tissue is limited and further affected by age and nutritional state).

Phase II: Stages of Regeneration:

• Stage starts with periphery• Re-eptheliaization is proliferation of peripheral

epithelial tissue which then migrates to the wound until the area is covered.

• Capillarization (Capillary buds proliferate and connect forming new capillaries which gives the red, granular appearance to the scar (granular tissue)

Phase II: Stages of Regeneration: Cont.

• Fibroplasia occurs due to fibroblasts which arises from undifferentiated mesenchymal cells and migrate into the area along fibrin strands and begin to synthesize scar tissue. • Scar tissue is CT and mostly collagen and

mucopolysaccharides. • Fibroblasts secrete both, contributing tensile strength

to the repair. • Scar tissue very inelastic compared to surrounding

tissue.

Phase II: Stages of Regeneration: Cont.

• Vascularization - occurs with the proliferation of collagen synthesis• Formation of blood vessels (angiogensis)

Phase II: Collagen Synthesis:

• Occurs within 12 hours of injury to 6 weeks (average 3 weeks)

• Type I: collagen: associate with muscular tissue (larger and stronger fibers)

• Type III collage: smaller fibers, less cross linking and highly disorganized (ligamentous, tendinous)

• Type III with time is replaced by Type I collagen

Phase II: Collagen Synthesis Cont.

• Tissue Healing Times• Muscle : approximately 3 weeks • Tendon: 4-6 weeks• Extent of the tissue damage and

vascularity will aid in determining healing time

• Age may also be a factor in healing

Phase II: Stages of Regeneration: Cont.

• Wound Contraction:• Wound contraction begins to occur in

CT as the myobroblasts (actin-rich fibroblasts) contract. Myofibroblasts move toward the center of the wound, helping reduce the size of the area to be covered.

• Outside-in

Phase III: Maturation/Remodeling Phase

• Purpose of this phase• Strengthen the repaired tissue• Firoblasts, myofobrpblasts &

Macrophages reduced to pre-injury state

• Type III fibrin continues to be replaced by Type I

Phase III: Maturation/Remodeling Phase (day 9 onward)

• Blends in with the repair phase, original collagen fibers were randomly oriented. During remodeling, the fibers become more organized, parallel to the wound surface which provides greater tensile strength

• The type of tissue involved will determine the duration and extent of remodeling activity

Phase III: Maturation/Remodeling Phase Cont.

• Strengthening of scar tissue continues from 3 months to 1 year, but fully mature scar in only 70% as strong as intact tissue.

• Motion will influence the structure and functional capacity of scar tissue (controlled stress increases functional capacity, allows healing and reduces adhesion formation).

Chronic Inflammation• Inflammation which continues past 1 month

• Marked by a loss of function• Fibroblast activity continues forming granuloma

Chronic Inflammation

• Complications• Granuloma: large mass of weaker scar

tissue (usually due to large inflammation and activity without regard to healing time)

• Retardation of muscle fiber: with excessive granuloma fibroblasts cannot reach damaged tissue

• Adhesions/contractures in tissue• Keloid/hypotrophic scars

Abnormal scarring:

• Hypertophic scar or keloid scar. Biological difference not well understood, but clinically hypertrophic scar is contained within the boundaries of the original wound while a keloid scar extends beyond the borders of the original wound.

Summary

O sm otic P ressureR esult edem a/sw elling

Lym phatic C hannels b locked

Vasodia lation

C hm eical M ediators R elease

M arg ination

Phagocytos is

Inflam m ationAp p rox im ate T im e Tab le

7-10 days(Acute phase 3 days)

Phase I:Acute Phase

Ap p rox im ate tim e tab le 2-3 w eeks

R egenerationScar tissue form ed

C ap ilarization

G ranulationF ib rob lasts lay dow n collagen

R esolutionM inor to no ce ll death

Phase II:T issue R epair

O ccurs for up to1 year

C ap illarization

R ep lacem ent of Typ e IIIco llagen w ith Type I

C ollagen

Phase III:M aturation P hase

In jury R esponseW ond H ealing

THE BIG QUESTIONS!

• When do we use cold?• When do we use heat?• When do we use medications?• When do we use Electrical modalities?

Treatment Planning for Phases of Tissue Healing

Phase I Phase II Tissue Healing

Phase III: Maturation

Control Active Inflam. Limit scope of Orig.

Injury

Encourage Repair/

Replacement Damaged Tissue

Encourage Tissue

Remodeling and Alignment with Func. Stresses.

Treatment Planning:Phase I Phase II Tissue

Healing Phase III:

Maturation

Immobilization Cold Modalities

Pulsed Ultrasound Compression

Elevation E-Stim

Contrast Baths Compression Devices E-Stim Pulsed/ Continuous US Traction Massage Biofeedback Heat Modalities

Heat Modalities Continuous US

E-Stim Massage

Treatment Planning: Maturation Phase

Phase I Phase II Tissue Healing

Phase III: Maturation

Cryokinetics Isometics Controlled ROM (CPM) Proprioception CV conditioning

Manual Therapy Passive ROM Active ROM Progressive Resistance Ex Functional Ex Cv Exercise

Overload Resistance Ex

Proprioception Ex Activity Specific

Functional Ex Cv Exercise

END OF TOPIC - A

Let us take a break (^_^)

INFECTION

Review of Physiology

• Resistance

A. Non-specific Resistance

- Body surface barriers

- Anti Microbial Secretions

- Internal Anti Microbial agents

- Phagocytosis part of the reticoendothelial

system

a. phagocytes

- Microphages

- Macrophages

• B. Specific Resistance

- lymphatic system

- lymph vessels

- lymph nodes

- lymph

- spleen

Specific Resistance (cont)

• Antigen

A. B-lymphocytes

B. T – Lymphocytes

C. Memory Cells

• Antibody

1. IgG

2. IgA

3. IgM

4. IgD

5. IgE

• Antigen – antibody reactions

a. Agglutination

b. Cytolysis

c. Opsonization

d. Neutralization (viral)

e. Neutralization (toxin)

f. Precipitation

Chain of Infection

Susceptible host

Portal of Entry

Etiologic Agent (microorganism)

Reservoir

Method of transmission from reservoir to (Source) susceptible host

Portal of exit

Pathogens

• Bacteria – Aerobic – Anaerobic

• Viruses - intracellular parasite capable of reproducing outside of a living cell.

• Mycoplasma – similar to bacteria and have no cell wall – resistant to antibiotics that inhibit cell wall synthesis

• Rickettsiae & Chlamydia- rigid cell wall; with some feature of both bacteria and viruses. – Chlamydia- transmitted by direct contact – Rickettsiae- infect cells of arthropods and are transmitted by these vectors.

• Fungi- self-limited, affecting the skin and subcutaneous tissue.

• Parasites

Reservoir

-where the pathogen lives and multiplies

– Endogenous

– Exogenous

• Mode of Transmission

– Direct contact

– Indirect contact

• Vector

– Droplet or airborne transmission

Host Factors

• Factors that enable a host to resist infections:

• Physical barriers

• Hostile environment created by stomach acid secretions, urine & vaginal secretions.

• Antimicrobial factors e.g. saliva, tears

• Respiratory defenses

• Specific and nonspecific immune responses to pathogenic invasion.

• Age

• Nutrition

Portal of Entry

• Respiratory Tract

• GI Tract

• Genitourinary Tract

• Skin and mucous membrane

• Bloodstream

Stages of Infectious Process

• Incubation period

– period begins with active replication but with no symptoms

• Prodromal stage

– Symptoms first appear

• Acute phase

– proliferation and dissemination of pathogens

• Convalescent stage

- containment of infection and pathogens are eliminated

• Resolution

– total elimination of pathogens without residual manifestation

Nosocomial infection

– Infection acquired in a health care setting.

– Typically manifest after 48 hrs.

– UTI most common type

FACTORS AFFECTING RISK OF INFECTION

• AGE• HEREDITY• LEVEL OF STRESS• NUTRITIONAL STATUS• CURRENT MEDICAL THERAPY• PRE-EXISTING DISEASE• IMMUNIZATION STATUS

Standard precautions

• Blood • All body fluids, secretions, excretions, • Non-intact skin • Mucous membranes

• Essential elements:

• Use barrier protection

• Prevent inadvertent percutaneous exposure, dispose of needles

• Immediate and thorough hand washing

Infection Control and Prevention

Infection Control in In-Patient Health Care Agencies

• Hand Hygiene• Patient Placement• Protective Equipment• Proper disposal of Soiled Equipment

Infection Control In Community – Based Setting

• Sanitation• Proper Disposal of Waste• Food Preparation• Report CD Occurrence