Healing and Repair II

6 steps of primary union

1. clot formation 2. inflammatory response 3. fibroblast and endothelial response 4. continuity of blood flow 5. epithelial regeneration 6. collagen formation

steps of secondary union

1. fibrosis 2. hemorrhage and blood coagulation 3. inflammatory response and phagocytosis of debris 4. large amount of fibrin is deposited --> granulation tissue grows from the wound margins 5. deficit begins to be filled in by granulation tissue, over time is completely filled in 6. matures to fibrous connective tissue with fibrocytes, decreased vascular presence, and collagen contraction (loss of adnexa)

5 factors that might delay healing/cause complications

1. strength of stimuli for cell division and proliferation 2. physiologic conditions 3. mobility of tissue 4. tissue type 5. immunodeficiencies

when is failure of passive transfer assessed?

18+ hours post birth

bovine leukocyte adhesion deficiency (BLAD): species

Holstein calves

how is stimuli strength supported?

adequate perfusion of injury deride dead tissue test for underlying hormonal imbalances exogenous administration of drugs (antibiotics, oral/injectable erythropoietin, topical creams/growth factors)

physiologic conditions that affect healing

age nutrition stress and endocrine factors blood supply infection temperature

severe combined immunodeficiency (SCID): arabian foals, JRT, mice clinical signs

appear normal, die from opportunistic infections

severe combined immunodeficiency (SCID): arabian foals, JRT, mice signalment

arabian and part Arabian foals jack russel terriers mice

toxins

artificial - antineoplastic chemotherapeutants natural - mycotoxins, heavy metals

hypotrichosis with thymic aplasia: signalment

birman cats and mice

how can too much or too little stimulation impede healing

blood perfusion underlying hormonal imbalances can decrease cell division genetic abnormalities infection and trauma trigger continued immune response

which type of immune deficiency directly affects innate immunity?

bocine leukocyte adhesion deficiency

canine cyclical neutropenia: treatment

bone marrow transfusion short term: bone marrow stimulants

what are the primary immunodeficiencies that can affect healing?

bovine leukocyte adhesion deficiency canine cyclical neutrophenia severe combined immunodeficiency hypotrichosis with thymic aplasa

effects of primary immunodeficiencies

can involve innate and/or adaptive immunity results in reduced quality or duration of life diagnosis is difficult, follows recurrent and difficult to treat infections

what is secondary closure?

contaminated wounds that need to be treated, cleaned, and granulation tissue has already formed prior to closure -begins secondary union, then begin suture

canine cyclical neutropenia: mechanism

cyclic lack of response of bone marrow to hematopoetic growth factors about every 2 weeks -all WBC affected, most pronounced in neutrophils

what is cell division and proliferation initiated by?

cytokines, growth factors, hormones

what type of immune system do geriatric animals have

decreased innate and adaptive immunity

what is important for mobility of tissues during healing?

dependent on timeframe and injury dependent best immobilized

how does tissue type impact healing?

different capacities to respond to injury and restore homeostasis

viral infections

direct infection of immune cells, lead to secondary infections

what happens during continuity of blood flow in primary union

endothelial proliferation mature to blood vessels that connect the margins of the wound -neovascularization

what happens during epithelial regeneration during primary union

epithelial cells grow from the sides towards the wounds edges

what species is failure of passive transfer most common in?

foals

what happens during clot formation

gap between the apposed tissues becomes sealed with coagulated blood

severe combined immunodeficiency (SCID): bassets and welsh corgis treatment

gene therapy bone marrow transplant

hypotrichosis with thymic aplasia: diagnosis

genetic testing

bovine leukocyte adhesion deficiency (BLAD): diagnosis

genetic testing for mutations in CD18 gene

what is the tissue known as during the fibroblast and endothelial response

granulation tissue

severe combined immunodeficiency (SCID):

group of genetic mutations that affect B- ad T- lymphocytes

which of these tissues has the highest capability to repopulate and restore tissue homeostasis? the lowest? bone cornea striated muscle

highest: cornea - epithelial cells = labile lowest: striated muscle - permanent cells

3 ways physiologic conditions associated with age can predispose to infection

hormonal diet decreased metabolism

what happens during inflammatory response of primary union

in response to injury and suture material acute - serohemorrhagic and fibrinous exudates + neutrophils chronic - macrophages

what happens during collagen formation during primary union

known as scarring very minimal deposition of collagen spares most of the adnexa within the dermis, wound is strengthened and contracts over a period of weeks to months

younger animals have what type of immune system

less robust

severe combined immunodeficiency (SCID): arabian foals, JRT, mice diagnosis

low lymphocytes on CBC agammaglobulinemia

severe combined immunodeficiency (SCID): bassets and welsh corgis signalment

male associated disease (xlinked)

severe combined immunodeficiency (SCID): bassets and welsh corgis mechanism

multi locus genetic mutation in certain cytokine receptors

when you observe granulation tissue in a lesion, what do you think?

must be chronic --> going on for a longer period of time

severe combined immunodeficiency (SCID): arabian foals, JRT, mice mechanism

mutation in DNA kinase which is important for developing lymphocyte receptors

hypotrichosis with thymic aplasia: mechanism

mutation in FOXN1 gene, godes for fur and thymus development -no fur, no production of T-lymphocytes

bovine leukocyte adhesion deficiency (BLAD): mechanism

mutation in the gene that codes for integrin controlling leukocyte adhesion and transmigration results in decreased inflammatory cell response and granule production

bovine leukocyte adhesion deficiency (BLAD): treatment

none

hypotrichosis with thymic aplasia: treatment

none

severe combined immunodeficiency (SCID): arabian foals, JRT, mice treatment

none

severe combined immunodeficiency (SCID): bassets and welsh corgis diagnosis

none

why is IgM normal in SCID

normal amount of lymphocytes but no class switching

bovine leukocyte adhesion deficiency (BLAD): clinical signs

oral ulcers periodontitis loss of teeth chronic pneumonia recurrent/chronic diarrhea

how is exudate resolved in inflammatory repsonse

phagocytes digest dead tissue and fluid is absorbed back into the blood stream and lymphatics

what species is temperature important in for healing/

poikilothermic animals

canine cyclical neutropenia: diagnosis

presentation, repeated CBC DNA test for autorecessive gene

what are the other 2 names for primary union?

primary healing healing by 1st intention

canine cyclical neutropenia: clinical signs

recurrent bacterial septicemia pneumonia gastroenteritis

severe combined immunodeficiency (SCID): bassets and welsh corgis clinical signs

recurring infections due to lack of t-cell response b-cells produce low IgG and IgA, normal IgM

treatment for failure of passive transfer?

replacement therapy and antibiotics

canine cyclical neutropenia: signalment

rough and smooth coated collies, present with diluted coat color

what does fibrin act as during primary union

scaffolding for endothelial cell and fibroblast proliferation

what are the other 2 names for secondary union?

secondary healing healing by second intention

what type of cells are involved with cell division and proliferation?

stabile cells and replacement of permeant cells by angiogenesis

hypotrichosis with thymic aplasia: clinical signs

thymic aplasia lack of CMI

why can bone marrow stimulants not be used long term?

toxic side effects

what are acquired immunodeficiency's that can affect healing?

viral infections toxins age failure of passive transfer

what 2 factors from nutrition contribute to collagen synthesis

vitamin c protein

what is healing by 1st intention?

wound edges are closely opposed

what is healing by 2nd intention?

wound edges are separated by a gap that must be filled in