Repair Flashcards
What is an abnormal connection between any 2 things in the body? Where is it inevitable?
Adhesion
side-effect of surgery
What is a common complication of adhesions requiring surgery?
intestinal obstruction
What is the process of replacing damaged tissue. Is it healing?
Repair
Repair is healing
What the are two forms of repair?
regeneration and scarring
What is repair with the growth of fully functional tissue to replace injured or dead tissue?
regeneration
T/F Total pure regeneration is rare.
true
What does regeneration require?
an intact connective tissue scaffold or only superficial injury (epidermal or epithelial layer only)
Healing with scarring replaces the injured or dead tissue with what? What is the function thereafter?
fibrous tissue lacking the specialized function of the tissue it replaces
Removal of one kidney causes compensatory hyperplasia and hypertrophy of the remaining kidney, which doubles in size
T/F this is regeneration
false, this is not regeneration
Removal of one lobe of the liver causes compensatory hyperplasia and hypertrophy of the remaining lobe, which generates the same volume of fully functional liver tissue as pre-removal
T/F this is regeneration
true
What is an excavation (a local defect) in the surface of an organ or tissue produced by sloughing (shedding) of inflamed necrotic tissue?
an ulcer
What is erosion?
superficial sloughing of mucosa (or epidermis)
T/F An ulcer is deeper than than an erosion
true
Why is it for physicians to know the difference bw erosion and ulcers?
Erosions heal by regeneration.
Ulcers are too deep to heal by regeneration and they scar.
Organs within the abdominal cavity are normally separated by what?
the peritoneal space
Lungs are normally separated from the chest wall by what?
the pleural space
heart is normally surrounded by what? Is it connected to it?
the parietal pericardium
not connected
Inflammatory material can create what between the surroundings of the organs if the spaces are compromised? If early, what are they composed of? later?
adhesions => abnormal connections between these things
early => adhesions are composed primarily of fibrin and are referred to as fibrinous
late => fibroblasts deposit collagen within them and they become fibrous
What is an abnormal opening between two places in the body?
fistula
What is a surgical connection between two things, commonly tubular structures?
anastomosis
A surgical anastomosis between tubular structures is usually not called a fistula except for the anastomosis between what?
anastomosis between an artery and vein in the arm created for the purpose of hemodialysis
Where do adhesions commonly occur?
between loops of bowel, bowel and peritoneum, fallopian tube and ovary, and lung and pleura
What type of adhesions are an inevitable side-effect of surgery?
fibrous adhesions
What is a common complication of fibrous adhesions tethering and kinking the bowel, with resultant loss of the lumen?
How is this treated?
intestinal obstruction
Regeneration requires what?
of stem cells
What has self-renewal capacity not present in mature cells?
stem cells
What type of replication do stem cells undergo? describe it
asymmetric replication:
in every cell division, one daughter cell retains self-renewing capacity and the other enters a differentiation pathway to a mature cell.
Describe the different types of stem cells
- Embryonic stem cells can give rise to any tissue (are pluripotent)
- Adult stem cells can only give rise to a limited number of tissues
- Induced pluripotent stem cells are derived from patient cells with embryonic stem cell genes introduced
Tissues can be categorized as labile, stable or permanent based on what?
the replicative capacity of their cells
Describe labile tissues
give examples of labile tissues
continuously lose cells and replace them by proliferation of mature cells and replacement of mature cells by stem cell proliferation
skin and the linings of the mouth, gastrointestinal tract, bladder, vagina, cervix, uterus, fallopian tubes and exocrine gland ducts, as well as the bone marrow, are all labile tissues
Describe stable tissues
give examples
composed of quiescent cells capable of proliferation, but not normally called on to proliferate
liver, kidney, pancreas, smooth muscle tissues, blood vessel linings and fibroblasts are stable cells and tissues
Describe permanent cells
give examples
do not proliferate except under extraordinary circumstances
parenchymal cells of the brain and heart (neurons and cardiac myocytes)
Continuously proliferating labile tissues are particularly vulnerable to what?
radiation injury
Radiation to skin causes what signs?
- erythema (redness),
- pruritis (itching)
- later desquamation (sloughing),
- and if hair-bearing, loss of hair
Radiation to the chest and abdomen causes what?
nausea, vomiting and diarrhea from the injury to the gastrointestinal tract.
Radiation to the bone marrow causes what?
leukopenia
What allows very high doses of radiation to be delivered to small areas in the treatment of malignant tumors, decreasing injury to surrounding tissue, but requiring computer-controlled multileaf collimators to precisely focus the radiation beam?
linear accelerators
Healing requires certain actions from a variety of cells. Name them
- monocyte migration to the site,
- fibroblast migration to the site,
- fibroblast proliferation,
- angiogenesis
- fibroblast collagen production
What orchestrates how tissues heal? Name them
- epidermal growth factor (EGF),
- fibroblast growth factor (FGF),
- platelet-derived growth factor (PDGF),
- transforming growth factor (TGF)
- vascular endothelial growth factor (VEGF)
What promotes fibroblast migration and proliferation?
EGF
What stimulates fibroblast migration and proliferation, as well as monocyte chemotaxis and angiogenesis?
FGF
What promotes fibroblast migration and proliferation along with monocyte chemotaxis and collagen making?
PDGF
What is the primary difference between PDGF and FGF?
PDGF is most prevalent early in the process when blood vessel disruption allows platelet contact with extracellular matrix
What stimulates fibroblast migration, monocyte chemotaxis and collagen making?
When is it most prevalent?
TGF-beta
more prevalent later in the course of repair
Monocyte chemotaxis is mediated by what?
- PDGF,
- FGF
- TGF-beta,
- other molecules
Fibroblast migration is promoted by what?
- PDGF,
- EGF,
- FGF
- TGF-beta
(EGF apparently being more repair-minded than inflammatory)
Fibroblast proliferation is mediated by what?
- PDGF,
- EGF,
- FGF,
- TGF-beta
Angiogenesis is promoted by what?
- FGF
- VEGF
Collagen synthesis is stimulated by what?
PDGF
TGF-beta
What prevents deficiency of any one growth factor from being rate-limiting?
Most growth factors have multiple roles and most roles can be played by multiple growth factors, so there is extensive redundancy,
Repair requires the production
extracellular matrix
What does the ECM consist?
basement membrane (underneath epithelium and around blood vessels) and interstitium, which is the supporting tissue between epithelium and vessels and between cells in connective tissue such as bone and cartilage
What is the basement membrane composed of?
- type IV collagen,
- laminin,
- heparan sulfate
- proteoglycans
The interstitium underneath the epithelium contains what? What do they form?
- fibrillar collagen,
- fibrillin,
- elastin,
- hyaluronic acid
- proteoglycans,
together form a three-dimensional amorphous gel
All types of collagen are composed of what?
3 polypeptide chains braided into a ropelike triple helix
What strengthens fibrillar collagen?
Fibrillar collagen is strengthened by lateral cross-link
Why should a medical student know the components of extracellular matrix?
There are diseases caused by defective genes for these components.
What are major components of healing tissue and resulting scars?
fibrillar collagens
The disease called Ehlers-Danlos syndrome (classical form) causes what? Genetically, what type of disease is this?
defective type V collagen that is weaker than normal, but this weakened collagen allows hypermobile joints and hyperextensible skin
disease has an autosomal dominant pattern of inheritance (affecting 50% of the children)
The vascular type of Ehlers-Danlos syndrome causes what? Where is it most prevalent?
defective type III collagen,
prevalent in blood vessels and bowel wall
What disease is characterized by having weak blood vessels and intestines that are prone to rupture?
vascular type of Ehlers-Danlos syndrome
What is due to deficiency of the enzyme lysyl hydroxylase, which impairs cross-linking of types I and III collagen, resulting in crooked spines?
Genetically, how is this disease characterized?
The kyphoscoliotic type of Ehlers-Danlos syndrome
disease has an autosomal recessive pattern of inheritance (affecting 25% of the children)
What is a glycoprotein secreted by fibroblasts? What is it a major component of?
Fibrillin
What serves as scaffolding for the deposition of tropoelastin?
microfibrils
What is an integral component of elastin?
tropoelastin
Elastin is particularly abundant where?
in the aorta and ligaments
Defects in the fibrillin gene cause what disease? characterize
Marfan syndrome
features a thin, elongated body habitus, with abnormally long arms, fingers and legs, and weak aorta, prone to dilatation and rupture.
as treatment for Marfan syndrome, Why are researchers looking at the loss of microfibrils leading to excessive TGF-beta?
microfibrils normally sequester TGF-beta, and that angiotensin receptor blocking medications inhibit the activity of TGF-beta
The function of the enzymes prolyl hydroxylase and lysyl hydroxylase are dependent on Vit C. What is their function?
catalyze the formation of the covalent bonds cross-linking fibrillar collagen
Deficiency of vitamin C causes what?
- weakened blood vessels, especially capillaries,
- resulting in bleeding (especially in skin and gums)
- poor wound healing.
Genetic defects in structural proteins tend to have what type of inheritance pattern?
an autosomal dominant pattern of inheritance
genetic defects in enzymes tend to have what type of inhertance pattern?
an autosomal recessive pattern of inheritance.
Describe Granulation tissue wrt what it contains and the color
healing tissue with residual chronic inflammatory cells (lymphocytes and macrophages), cellular debris, fibroblasts, neovascularization and new collagen
Granulation tissue is commonly red or pink,
soft and granular grossly
What is regarded as the feature most characteristic of granulation tissue?
angiogenesis
What are regarded as the feature second most characteristic of granulation tissue?
Proliferating activated fibroblasts
What makes early granulation tissue soft?
new, small and numerous blood vessels of early granulation tissue are leaky and the fluid that leaks out of them
What is the process replacing injured, necrotic and inflamed tissue by healing and scar tissue?
organization
The key cellular player in the process of organization is what?
fibroblast
What would allow a physician tissue is organizing?
seeing fibroblasts in a thrombus, an inflammatory exudate or a wound
Describe the presence of macrophages different times of appearance as well as how long they persist wrt to skin and heart
**skin wounds=> **macrophages appear early, soon peak and rapidly depart.
**myocardial infarctions=> **macrophages appear later, slowly peak and persist for weeks into healing.
What is the formation of new blood vessels in healing tissue?
Angiogenesis (neovascularization)
T/F Angiogenesis can occur in healing tissue, tumors, atherosclerosis
true
Angiogenesis is mediated by VEGF? What is the function of this growth factor?
VEGF
increases vascular permeability as well as endothelial migration and proliferation
VEGF production is induced by what?
- TGF,
- PDGF
- hypoxia
In skin wounds, angiogenesis starts when? When does it peak?
begins early, soon peaks (at day 5 with a clean straight wound)
rapidly dissipates (during the second week)
In MI, angiogenesis starts when? When does it peak?
begins simultaneously with fibroblast infiltration at the periphery on day 4,
new blood vessels persist for weeks into healing
Wound healing in general and skin wound healing in particular has three overlapping phases…
- Inflammation,
- Proliferation (granulation tissue)
- Maturation (wound contraction)
describe healing by first intention
Surgical incisions of the skin, when they are clean, uninfected and have their edges approximated by sutures, can heal especially quickly and well
describe by second intention
occurs with larger wounds with (commonly irregular) edges, not approximated by surgical sutures
Describe the process of healing by first intention
- narrow space left by the incision fills with blood clot and within 24 hours
- day 1, neutrophils infiltrate this clot from margins => early phase (inflammation)
- day 2, epithelial cells proliferate, move into clot filling cleft, extending cut margin of basement membrane as they go.
- day 3, macrophages infiltrate & replace neutrophils, and thickening epithelial cells
- day 4, fibroblasts infiltrate, proliferate & lay down collagen, initially @ margins, vertically oriented and not bridging the gap filled by the clot
- day 5, granulation tissue fills space created by incision & angiogenesis reaches its peak
day 5 =>Collagen is now more abundant and beginning to bridge the incisional space. epidermis tends to reach its normal thickness and its mature architecture, with keratin formation
Describe the process of healing by second intention
- larger blood clot fills space of wound.
- There is more intense inflammation and more granulation tissue.
- wound contraction performed by myofibroblasts
- 3rd phase => (Maturation or wound contraction) is a matter of tissue remodeling (alter cell content & ECM)
- results in SCAR FORMATION and epidermal layer is thinner than normal
What is lost as a result of healing by second intention?
Skin appendages, such as sweat glands, present in the area of the skin wound are lost
T/F Blood clotting and inflammation are inexorably and intricately linked.
true
What is the high point of healing? Why is this important?
proliferative phase
peak of granulation tissue with most characteristic angiogenesis and fibroblast proliferation
The most important growth factor driving angiogenesis is what? What type of molecule is this?
VEGF
family of VEGF and placental growth factor
The family of VEGFs and placental growth factor has what effect?
stimulate migration and proliferation of endothelial cells at the site of injured blood vessels, which sprout new blood vessels.
When can neovascularization more harmful? How is this treated?
more harmful than helpful to vision in some retinal diseases such as “wet” (neovascular) diabetic retinopathy, macular degeneration and retinopathy of prematurity.
Antibody to VEGF can be injected into the eye to treat
most important growth factor driving fibroblast migration, proliferation and collagen synthesis is what?
TGF-beta
Other than TGF-beta, what also promotes fibrogenesis?
PDGF, FGF, and EGF
Extracellular matrix is continuously remodeled throughout the body through breaking down collagen and other matrix components. What carries this out?
matrix metalloproteinases
What metal are the MMPs dependent on?
zinc
activity of MMPs needs tight control. How is this accomplished?
by tight control of their synthesis and secretion
inhibited by specific tissue inhibitors of metalloproteinases (TIMPs)
(Proper tissue remodeling requires a fine balance of MMPs and TIMPs.)
T/F In general, the more distal on the legs a wound is, the slower it heals
true
What can impair wound healing?
- Infection,
- poor perfusion,
- diabetes mellitus,
- corticosteroids,
- foreign material,
- anemia,
- poor nutrition,
- mechanical stress,
- obesity,
- chemotherapy,
- radiation
- fibroblast aberrancy
What is the most important cause of impaired wound healing?
Infection
Why in general do wounds heal more slowly in old people?
large part of the reason is poor perfusion of the wound due to atherosclerotic vascular disease limiting blood flow
Describe how Diabetes mellitus delays wound healing
primarily because of the small blood vessel disease associated with it (microangiopathy)
also predisposes to infection by pouring excess sugar into the wound, providing food for infecting organisms and making neutrophils lazy.
Describe how corticosteroids impair wound healing? What type of metabolic function do they have?
inhibit protein synthesis in general and collagen synthesis in particular;
they are catabolic, but wound healing requires anabolism.
What decreases the oxygen delivered to the site of repair?
Anemia
What is a special problem with the healing of bone fractures?
Mechanical stress
Describe how mechanical stress can cause a non-union fracture
Motion of the healing margins of the two broken ends of a long bone fracture can prevent them from meeting up
If scratching detaches the scab prematurely, this can disrupt what?
underlying partial epidermal layer and granulation tissue, setting back the healing process.
What is the rupture of a surgical wound or anastomosis?
Dehiscence
What is the protrusion of a body part somewhere it does not belong?
hernia
Dehiscence of a surgical wound
most common with what? with surgical anastomases?
- surgical wound=>abdominal surgery associated with high intra-abdominal pressure
- surgical anastomoses is most common with bowel anastomoses, associated with infection
What is hypertrophic scar, more common in African-Americans?
Keloid
What is abnormal excess wound contraction resulting in deformity and impaired movement? Where are these typically found?
Contracture
- palms (Dupuytren’s contracture),
- soles (Lederhosen disease)
- penis (Peyronie disease).
Fibrosis is excessive interstitial collagen deposition. What is the result? What is this due to?
commonly replacing normal functional (parenchymal) tissue
- usually due to chronic inflammation,
- recurring injury (e.g. alcoholic hepatitis, pancreatitis),
- persistent toxin (e.g. silica, asbestos),
- radiation
- autoimmune attack
What causes the worst fibrosis? why?
Autoimmune diseases
the inciting agent (some component of oneself) is continuously present and cannot be limited or eliminated
What causes gradually progressive fibrosis of the fingers until they are fixed into a partially closed “claw hand”, sometimes with gangrene of the fingertips or even autoamputation?
systemic sclerosis (scleroderma)
What happens when the esophagus undergoes fibrosis?
obliterating both normal peristalsis to move food from the oropharynx down into the stomach and the lower esophageal sphincter for holding food in the stomach.
Regurgitation from fibrosis leads to what
aspiration pneumonia
What type of fibrosis will lead to renal failure?
Sclerosis of interlobular arteries in the kidney
What is process of replacing damaged tissue by regeneration and/or scar?
Repair:
What is healing tissue with lymphocytes, macrophages, fibroblasts, neovascularization and new collagen?
Granulation tissue:
What is the process replacing injured, necrotic and inflamed tissue by healing and scar tissue, carried out by fibroblasts?
Organization:
What is excessive interstitial collagen deposition?
Fibrosis:
Complications of wound healing
include (4)
- Dehiscence
- Herniation
- Keloid
- Contracture
Granulation tissue is healing tissue with what 5 things
- macrophages
- lymphocytes
- fibroblasts
- neovascularization
- new collagen
With terminology, name early adhesions and late adhesions
Fibrinous = early
Fibrous = late, requiring scalpel or
scissors to separate
