Inflammatory Process

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

– This is what we try to do as therapists through modality use

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 cycle

Phases of the Inflammatory Process

• Phase I: Acute Phase– inflammatory response: lasts 2-4 days but is complete in 2

weeks

• Phase 2: Tissue Formation (Proliferation)– Subacute phase, 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: 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 reased 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 tia l flu id cau s in g ed em a/sw e llin g

S w e llin g /ed em a are 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 calls exudation.

Phase I: 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: 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: Margination Cont.

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

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

Phase I: Early Phase Inflammation - 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 hours

Phase I: 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

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

– Fibrobalsts are connective tissue responsible for collagen synthesis

• Ligaments, joint capsule, tendon

– Osteoblasts: responsible for bone synthesis

Fibropblast Macrophages

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, myofobrpb;asts & Macrophages

reduced to preinjury state– Type I fibrin continues to be replaced by type

III

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 ationApp rox im ate T im e Tab le

7-10 days(Acute phase 3 days)

Phase I:Acute P hase

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

R eg enerationScar 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 Type 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: Phase I - Inflammation

Phase I Phase II TissueHealing

Phase III:Maturation

Control ActiveInflam. Limitscope of Orig.

Injury

EncourageRepair/

ReplacementDamaged Tissue

EncourageTissue

Remodeling andAlignment withFunc. Stresses.

Treatment Planning: Proliferation Phase

Phase I Phase II TissueHealing

Phase III:Maturation

ImmobilizationCold Modalities

Pulsed UltrasoundCompression

ElevationE-Stim

Contrast BathsCompressionDevicesE-StimPulsed/Continuous USTractionMassageBiofeedbackHeat Modalities

Heat ModalitiesContinuous US

E-StimMassage

Treatment Planning: Maturation Phase

Phase I Phase II TissueHealing

Phase III:Maturation

CryokineticsIsometicsControlled ROM(CPM)ProprioceptionCV conditioning

Manual TherapyPassive ROMActive ROMProgressiveResistance ExFunctional ExCv Exercise

OverloadResistance Ex

Proprioception ExActivity Specific

Functional ExCv Exercise