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