BOC study flash cards: Intro to TI and Healing Process

Arndt-Schultz principle

Insufficient energy to stimulate target structure results in no reaction or change, and too much energy is detrimental to tissue.

Law of Grotthus-Draper:

There is an inverse relationship between energy absorption and penetration.

Mechanisms of energy exchange

reflected, transmitted, refracted, and absorbed.

Inverse Square Law

Amount of energy transferred relates to inverse square of the distance between objects.

Cosine law

•The greater the angle between the beam of energy and the surface, the less the amount of energy transfer.

•If ultrasound waves strike at 30°angle à 86% of the effect.

Negligence: omission

Not doing: Neglecting to take a necessary step or withholding information (e.g., neglecting to report a danger).

Negligence: comission

doing: Taking an action that causes a problem (e.g., actively spreading false information).

stages of tissue healing

•Inflammatory (Acute)

•Proliferation (Repair)

•Remodeling (Maturation)

Tissue healing: immediate response

Vasoconstriction- Seconds-minutes (~8)

•Platelets adhere to the capillary
wall to form a “plug”

Primary Hemostasis: Epinephrine & Thromboxane A₂

Tissue healing: immediate response cont.

Coagulation Cascade: Platelets release to cause hemostasis by forming a platelet plug, activates:

Prostaglandins & thromboxane (A₂ -> B₂)

•Secondary Hemostasis

•Platelets aggregation and fibrin formation:

•fibrinogen → fibrin forms a "Clot”

Cytokines

•Substance from cell found in the immune system

•Signaling proteins that initiate the mediated events

•Various mediated events:

•Chemotaxis – movement 

•Mitogen – growth

•Differentiation – development  

•Interleukin family of proteins (11) have a role  in inflammation and immune response 

•Pro-inflammatory 

Plasma protein mediated event

•Inactive proteins are activated -> called cascades

•Clotting, Kinin and Compliment Cascades

•All three cascades:

•Interact and occur simultaneously

•Function with chemical mediators from mast cells that facilitates the protein cascade

•Activated by antigen-antibody response, bacteria chemicals released from damaged cells

Clotting cascade

•Triggered by  damage to the RBC

•Releases thromboplastin → prothrombin to thrombin then:

•Converts fibrinogen → fibrin

•Form a fibrous framework of tissue repair

•Prevents blood loss

•Hageman’s factor XII → activate XI and prekallikrein → kallikrein

•Activates the Kinin cascade 

Kinin cascade

•Kallikrein → Kininogen→ forms bradykinin

•Bradykinin:

•peptide released in the blood and causes the dilation of blood vessels.

•increases the membrane permeability  of capillaries

•Interacts with Prostaglandins (PG or PGE₂) 

•PG works with Bradykinin to increase permeability

•Both irritate free nerve endings to cause the pain.

Compliment cascade

•Impacts all inflammatory response

•Increases capillary membrane permeability

•Chemical attraction of leukocytes

•Leukocytes fall out of circulation due to the increase in membrane permeability.

•Mast cell degranulation

•Cytotoxins are released that causes cell death

•Phagocytosis

Mast cell mediated event

•Mast Cells (in connective tissue) triggers a release of histamine and serotonin results -> vasodilation

•Damaged tissue releases cytokines

•Triggers release of arachidonic acid (AA)

•Arachidonic Acid forms PGE

•Contains PGE, leukotrienes and lipoxins

endogenous anti-inflammatory, helps reduce excessive tissue injury and chronic inflammation.

histamine

•strong vasodilator (redness and heat)

•Slows circulation, causes hemoconcentration  

serotonin

•increase permeability (swelling)

•Plasma proteins escapes, attracts water and exert osmotic pressure

•Brings leukocytes or WBC (neutrophils & monocytes) for phagocytosis

heparin

an anticoagulant is released to prevent clotting 

phospholipid breakdown

•Leukotrienes: a chemical that attracts Leukocytes

•Leukotrienes & PG release free radicals (protease) that breakdown collagenase

reactive oxygen species (ROS)

•Free radicals are a by-product of AA releasing PGE

•Activates proteases such as collagenase

•Collagenase is an enzyme that breakdown collagen

may result in secondary hypoxia

leukocyte mediated event

•Cytokines activates Leukocytes to go to damaged cells

•Leukocytes are found in stem cells in bone marrow

•Neutrophils are predominant (90%) …monocytes and lymphocytes

•High in number, short life span, body produces WBC on a daily basis

•Neutrophils are the first to arrive and is the primary granulocyte initially (peaks at 24 hours)

•Strong bactericidal, and antimicrobial enzymes

neutrophil roles

•Cleans area by degrading the damaged tissue

•Releases Chemokines that attracts Monocytes

monocytes and macrophages

•Monocytes (M₁, M₂) mature into macrophages.

•Macrophages finishes phagocytizing necrotic tissue

•Peak at 3-7 days, but continues until all debris and dead cells are removed

•Has a role in cell recruitment, angiogenesis, and building and remodeling of the matrix

•therefore continues into the proliferation and remodeling stages.

m1 macrophages

•Cytokine activated

•Pro-inflammatory

•Peak 0-4 days

•Phagocytic

•Resolve once inflammation is gone

•Inflammation recedes in ~1-5 days

m2 macrophages

•Cytokine inhibited

•Anti-inflammatory

•Regulated by AA metabolism and lipoxin production

•Binds with Formyl peptide receptors (FPRs)

•Decrease granulocyte and cytokine release, and chemotaxis

proliferation phase

•Cell proliferation peaks at 6 days, continues ~2 weeks  

•Fibroblasts (in tissue and circulation) are activated

•Fibrocytes (in monocytes) can also differentiate into other cells.

•M₂ macrophage cytokines stimulate fibroblast production

•rebuilds tissue, begins with a provisional matrix.

•activates progenitor cells to replenish the reparative cells

•Cell type is dependent on the tissue type .

labile cells

•Epidermis, bone, GI & GU Systems, respiratory

•Easily regenerated

stabile cells

•Liver, pancreas, kidneys

•Fibroblasts synthesizes collagen & elastin

•Ligaments & tendons

•Osteoblast and osteocytes -> bone

•Chondroblast and chondrocytes -> cartilage

•Regenerates, but not as well

permanent cells

•CNS, corneal lenses, cardiac mm

•Do not regenerate

•Cellular plasticity = alter behavior or phenotype

skeletal cells

•Repair by laying down tissue “scarring”

•Fibroblasts forms collagen III -> I

•Regeneration occurs, but difficult to return to pre-injury state (3 day -2 weeks)

remodeling stage

•Dense & unorganized matrix of collagen fiber must be organized.

•Activated fibroblasts produce Type I collagen.

•Develop fiber alignment

•Cross fibers become stronger

•Scar formation ~4 months to mature

•Scar ~95% of original tissue.

•Fibrosis is a concern

•Must permit inflammatory process to proceed through the appropriate timeline.

•Chronic inflammation must be eliminated. 

tendon healing

•Endotendon, epitenon, fascicules, Paratendon, tendon sheath

•Poor vascularity

•3-7 days for cessation of inflammatory response

•~3weeks for proliferation of ECM

•5-8 weeks to remodel Type II to Type I collagen fiber

ligament healing

•Vascularity: 

•Good with extra articular ligaments 

•Poor with intra articular ligaments

•3-7 days for inflammatory response

•3 weeks proliferation of ECM

•5-8 weeks for Type II -> I collagen fiber

bone healing

•Osteon, osteoblasts, osteocytes, intercellular matrix

•Mesenchymal stem cells and platelet-release cytokines -> inflammatory receptors

•Injury -> osteocytes trigger an ECM in 2-5 days

•Type III -> Type II and Type I  takes 2-12 months  

cartilage healing

•Avascular, Aneural, alymphatic

•Poor regeneration

causes of swelling

1.Increase in capillary membrane permeability

•Leukocytes enter the damaged area

•Plasma proteins leak out, attract water due to osmotic pressure

2.Dead cells

•Free proteins form on capillary wall & interstitium

3.Nutrients, gasses arrive via hydrostatic pressure

4.Plasma proteins clog venule end of capillaries

•Reverse osmotic pressure → water & debris reabsorbs

•Damaged cells absorbs via lymphatic system

Window of opportunity

8 minutes