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Flashcards in Path: Repair Deck (120):
1

Name the two forms of repair.

Regenerating and scarring

2

Describe the regenerating form of repair.

Repair with the growth of fully functional tissue to replace injured or dead tissue.

3

Total pure regeneration of injured tissue is rare. Explain why.

It requires an intact connective tissue scaffold or only superficial injury (epidermal or epithelial layer only).

4

Explain the process of scarring repair.

It replaces the injured or dead tissue with fibrous tissue lacking the specialized function of the tissue it replaces.

5

Name the one organ capable of regeneration to replace the function of excised tissue.

Liver. Amazing. The liver is Amazing.

6

T/F: erosions heal by regeneration.

True.

7

T/F: ulcers heal by regeneration.

False. Erosions are too deep to heal by regeneration alone and thus, they scar.

8

Describe......an adhesion!

An abnormal connection between any two things in the body. Like your nose to your elbow. That may be an adhesion secondary to PKU.

9

Describe the character of an early adhesion.

Early on, adhesions are composed primarily of fibrin and are referred to as fibrinous.

10

Describe the character of a late adhesion. Ready, GO!

Later, fibroblasts deposit collagen within them and they become fibrinous, requiring a scalpel or scissors or a broad sword to separate.

11

What is a fistula again?

An abnormal opening between two places in the body. Like your PP fossa to your elbow. Might be secondary to PKU as well.

12

What differentiates a fistula from an anastamosis?

An anastamosis is a surgically formed fistula. It belongs there. Unlike PKU.

13

WHO (cell type) IS RESPONSIBLE FOR ALL THIS SCAR TISSUE??

Wretched fibroblasts! Who hired those clowns? Was it you mesenchyme? You're fired. You have until the afternoon to pack all your things. No, leave the ficus, that belongs to the office.

14

Who are the key players in repair?

Fibroblasts.

15

Why is the cytoplasm of fibroblasts so basophilic?

Has lots of RNA.

16

Let's say a fibroblast is capable of contracting. Then what is it called? Also, why is this relevant to scars?

Myofibroblast. In the process of healing with scar, myofibroblasts contract and tighten up the evolving scar. As a result, scars are smaller than whatever they replace.

17

When their job is done, fibroblasts go into reserve mode or retire (with a great pension). What are these fibroblasts called?

fibrocytes. (kind of like osteocytes after osteoblasts are done laying down bone)

18

Regeneration requires the proliferation and differentiation of _____ cells.

Stem cells.

19

Describe the process of asymmetric replication and what cells undergo such a fascinating thing.

Stem cells undergo asymmetric replication: in every cell division, one daughter cell retains self-renewing capacity and the other enters a differentiation pathway to a mature cell (it will no longer be a stem cell).

20

Describe the 3 type of stem cells.

Embryonic: can give rise to any tissue (pluripotent)

Adult: can only give rise to a limited # of tissues

Induced pluripotent: derived from patient cells with embryonic stem cell lines introduced. The hope is to grow a pt's own cells into replacement tissue/organs for any pt who needs replacement.

21

Tissues can be categorized as _______, ________ or _________ based on the replicative capacity of their cells.

labile, stable or permanent

22

Describe the replicative capacity of labile tissues. Give 3 examples of such tissue.

Labile tissues continuously lose and replace cells by proliferation of mature cells and replacement of mature cells by stem cell proliferation.
ex: GI tract, bladder, vagina, cervix, uterus, fallopian tubes, exocrine gland ducts, bone marrow.

23

Describe the replicative capacity of stable tissues. Give two examples.

Composed of quiescent cells capable of proliferation, but not normally called on to proliferate.
ex: Liver, kidney, pancreas, smooth muscle tissues, blood vessel linings, fibroblasts.

24

Describe the replicative capacity of permanent cells and give two examples.

Do not proliferate except under extraordinary circumstances.
ex: parenchymal cells of brain and heart

25

Which of the 3 tissue types is most vulnerable to radiation injury?

Labile.

26

Quiescent cells are in the ____ stage of the cell cycle.

G0

27

To proliferate, quiescent cells progress through the ____ (presynthetic growth) phase, the ___ (DNA synthesis) phase, ___ (premitotic) phase and ___ (mitosis) phase of the cell cycle.

G1
S
G2
M

28

Cell cycle progression is driven by ______ and associated ________________.

cyclins; cyclin-dependent kinases (CDKs)

29

In cell cycle progression, cyclin-dependent kinases (CKDs) ______ the various proteins needed at each phase and then cease their contribution as their associated cyclins are ________.

phosphorylate; degraded

30

In the cell cycle, between ____ and ____ phases, there is a checkpoint where DNA is checked for imperfections before it is duplicated.

G1 and S

31

Big DNA imperfections detected between G1 and S phase of the cell cycle trigger:

apoptosis

32

In the cell cycle, between ___ and ____ phases, there is another checkpoint where the duplicated DNA is checked for defects, triggering repair for small ones and _______ for big ones.

G2 and M; apoptosis

33

The liver has a unique and amazing ability to regenerate itself with resection of up to ____% of its parenchyma.

90% HOLY SHIT. First round's on me!

34

Regarding hepatocyte proliferation in regeneration:
There is a priming phase wherein _____ stimulates Kupffer cells to secrete ______, which primes the hepatocytes.

TNF; IL-6

35

Regarding hepatocyte proliferation in regeneration:
Following Kupffer cell secretion of IL-6 to prime hepatocytes, there is a growth phase wherein primed hepatocytes are stimulated by ______ and hepatocyte growth factor (HGF) to leave ____ (phase) and enter the _____ phase of the cell cycle.

TGF-alpha; G0; G1

36

Regarding hepatocyte proliferation in regeneration:
When regeneration is completed, there is a termination phase wherein the hepatocytes return to their _____________ state. This phase is thought to be most likely mediated by ________.

quiescent G0 state; TGF-beta

37

When the liver is injured by inflammation or toxins like alcohol, it can regenerate from _______ cells. Some of these cells reside in the __________ where bile canaliculi connect with larger bile ducts.

progenitor; canals of Hering

38

________ are usually present and often prominent around nodules of regenerating hepatocytes in liver repair from chronic hepatitis.

Proliferating bile ductules

39

_______ orchestrate the migration of monocytes, fibroblasts, fibroblast proliferation, angiogenesis and collagen production, along with other shit at the site of injury for healing.

growth factors

40

Name 5 of the more important growth factors involved in the process of repair.

Epidermal growth factor (EGF)
Fibroblast growth factor (FGF)
Platelet-derived growth factor (PDGF)
Transforming growth factor (TGF)
Vascular endothelial growth factor (VEGF)

41

Describe the action of EGF to aid in the repair process of injured tissues.

Stimulates fibroblast migration, fibroblast proliferation and collagenase secretion.

42

Describe the action of FGF to aid in the repair process of injured tissues.

stimulates fibroblast migration to repair sites and fibroblast proliferation, as well as monocyte chemotaxis and angiogenesis and collagenase secretion.

43

Describe the action of PDGF to aid in the repair process of injured tissues.

Promotes fibroblast migration to repair sites, fibroblast proliferation and monocyte chemotaxis, along with collagen synthesis, but also collagenase secretion.

44

_______ is most prevalent early in the process of injury repair when blood vessel disruption allows platelet contact with extracellular matrix.

PDGF

45

Describe the action of VEGF to aid in the repair process of injured tissues.

Mediates angiogenesis. Does nothing else!

46

Describe the action of TGF-beta to aid in the repair process of injured tissues.

Chemotactic for neutrophils, lymphocytes, macrophages, fibroblasts and smooth muscle cells. Stimulates tissue inhibitors of MMPs, stimulates karatinocyte migration, angiogenesis and fibroplasia, as well as promoting collagen synthesis.

47

______, is probably the most important growth factor in inflammatory fibrosis.

TGF-beta.

48

T/F: TGF-beta promotes production of TGF-beta.

True

49

________ activated by injury are the most important source of growth factors mediating repair.

Macrophages

50

Monocyte chemotaxis of repair to tissue injury is mediated by what GFs?

PDGF
FGF
TGF-beta

51

Fibroblast Migration of repair to tissue injury is mediated by what GFs?

PDGF
EGF
FGF
TGF-beta

52

Fibroplast Proliferation of repair to tissue injury is mediated by what GFs?

PDGF
EGF
FGF
TGF-beta

53

Angiogenesis of repair to tissue injury is mediated by what GFs?

FGF
VEGF
TGF-beta

54

Collagen synthesis of repair to tissue injury is mediated by what GFs?

PDGF
TGF-beta

55

Basement membranes are composed of which notable collagen type?

Type IV

56

Name the 4 fibrillar collagens. and describe their character.

I
II
III
V
Composed of 3 polypeptide chains braided into a rope-like triple helix. Strengthened by lateral cross-links.

57

_______ deficiencies are collectively the most common disorders of connective tissue.

Collagen deficiencies

58

The net result of the 4 types of osteogenesis imperfecta is:

fragile bones, which fracture easily with minor trauma and heal poorly.

59

Ehlers-Danlos syndrome (classical form) causes defectie type _____ collagen that is weaker than normal, but this weakened collagen allows ________ joints and ______ skin.

type V collagen; hypermobile joints; hyperextensible skin

60

The vascular type of Ehlers-Danlos syndrome causes defective type ___ collagen, which is prevalent in blood vessels and bowel wall.

Type III collagen.

61

The kyphoscoliotic type of Ehlers-Danlos syndrome is due to deficiency of the enzyme lysyl hydroxylase, which impairs cross-linking of types ___ and ___ collagen, resulting in crooked spines.

types I and III collagen

62

Classic and vascular types of Ehlers-Danlos have what mode of inheritance?

Autosomal dominant

63

The kyphoscoliotic type of Ehlers-Danlos has what mode of inheritance.

Autosomal recessive

64

_______ is a glycoprotein secreted by fibroblasts and a major component of microfibrils, which serve as scaffolding for the deposition of _______, which is an integral component of elastin, which is particularly abundant in the aorta and ligaments.

Fibrillin; tropoelastin

65

Defects in the fibrillin gene cause ______ syndrome which features thin elongated body habitus, with abnormally long arms, fingers and legs, and weak aorta, prone to dilation and rupture.

Marfan syndrome

66

The enzymes prolyl hydroxylase and lysyl hydroxylase catalyze the formation of the covalent bonds cross-linking fibrillar collagen and this is dependent on ________.

Vitamin C

67

Genetic defects in structural proteins tend to have a _________ pattern of inheritance whereas genetic defects in enzymes tend to have a _________ pattern of inheritance.

Autosomal dominant; autosomal recessive

68

________ tissue is healing tissue with residual chronic inflammatory cells (lymphocytes and macrophages), cellular debris, fibroblasts, neovascularization and new collagen.

Granulation tissue

69

In pathology, _______ is the process of replacing injured, necrotic and inflamed tissue by healing and scar tissue.

Organization

70

The key cellular player in the process of organization is the...

FIBROBLAST!

71

VEGF production is mediated by two growth factors and one circumstance:

TGF, PDGF and hypoxia

72

Describe the chronology of angiogenesis in skin wounds.

Begins early, peaks at day 5 (with a clean, straight wound) and rapidly dissipates (during the second week).

73

Describe the chronology of angiogenesis in myocardial infactions.

Angiogenesis begins simultaneously with fibroblast infiltration at the periphery of the infarcted tissue on day 4, and the new blood vessels persist for weeks into healing.

74

Describe the 7 steps of angiogenesis.

1) Existing blood vessel dilates in response to NO. VEGF causes vessel to vasodilate and become more permeable.
2) Pericytes detatch from their blood vessel and basement membrane breaks down at site of pericyte detatchment
3) Endothelial cells migrate to site of BM breakdown.
4) Endothelial cells proliferate
5) Aggregate of proliferated endothelial cells remodeled into a capillary tube w/ lumen
6) Pericytes recruited to more fully develop new BV.
7) BM extends along new BV as further endothelial cell migration and proliferation is inhibited.

75

How does the monoclonal Ab Bevacizumab treat various cancers?

It blocks the action of VEGF in promoting angiogenesis to expanding tumor.

76

List 5 growth factors important to angiogenesis.

VEGF, FGFs, angiopoetins, PDGF and TGF-beta

77

Regarding angiogenesis:
_____ (GF) stimulates endothelial cell proliferation.

FGF

78

Regarding angiogenesis:
_________ (GF) recruit pericytes and smooth muscle cells (for arterial walls).

angiopoetins

79

Regarding angiogenesis:
_______ (GF) recruits smooth muscle cells for arteries.

PDGF

80

Regarding angiogenesis:
_______ is important for limiting the process to where it is needed at sites of injury.

TGF-beta

81

Regarding angiogenesis:
___________ signaling regulates the sprouting and branching of new blood vessel to coordinate this with the healing needs of damaged tissue.

Notch pathway

82

Extracellular matrix proteins interact with ________ on endothelial cells to provide the scaffolding for angiogenesis.

integrins

83

_______ remove ECM in the way of growing blood vessels.

MMPs (matrix metalloproteinases)

84

What metal do MMPs depend on for their action?

Zinc

85

Name the 3 overlapping phases of cutaneous wound healing.

Inflammation
Proliferation (granulation tissue)
Maturation (wound contraction)

86

What is healing by "first intention"?

Surgical incisions of the skin, when clean, uninfected and edges approximated by sutures. Heal especially quickly and well.

87

What is healing by "second intention"?

Large wounds with commonly irregular edges, not approximated by surgical sutures.

88

What happens within 24 hrs of incision in healing by first intention?

Incision fills with blood clot and neutrophils infiltrate the clot from the margins.

89

Regarding healing by first intention:
On what day do epithelial cells proliferate and move into the clot filling the cleft, extending the cut margin of the basement membrane as they go?

Day 2

90

Regarding healing by first intention:
What happens on day 3?

Macrophages infiltrate and replace neutrophils. Proliferation of epithelial cells thickens the renewing epidermis under the scab.

91

Regarding healing by first intention:
What happens on day 4?

Fibroblasts infiltrate, proliferate and lay down collagen.

92

Regarding healing by first intention:
What happens on day 5?

Granulation tissue fills the space created by the incision and angiogenesis reaches its peak. Collagen is now more abundant and beginning to bridge the incisional space. Epidermis reaches normal thickness, w/ keratin formation. Residual surface clot, the scab, loosens.
Mnemonic: ABC-EFG (no D)
A-angiogenesis / B-bridge of collagen / C-clot or scab loosens / E-epidermis reaches normal thickness / F-formation of keratin / G-granulation tissue

93

Regarding healing by first intention, how long does it take a wound to completely heal?

1 month

94

Regarding wound healing by second intention, what makes the end result crappy compared to healing by first intention?

More intense inflammation during healing.
Wound contraction by 5-10%
Scar formation
Epidermal layer is ultimately thinner than normal
Skin appendages, such as hair, sweat glands, are lost
Skin wound strength by day 7, when compared to first intention healing, is 10%.
Skin wound strength at month 3 is about 75% of normal skin and remains so for LIFE.

95

What are the two most characteristic features of the proliferative phase of wound healing?

Angiogenesis
Fibroblast proliferation

96

What is the most important GF driving angiogenesis?

VEGF

97

Name a disease in which angiogenesis is more harmful than good (besides tumors). What mAB is injected to treat this and what does it act on?

Retinopathies
Bevacizumab, blocks action of VEGF

98

What is the most important growth factor driving fibroblast migration, proliferation and collagen synthesis?

TGF-beta

99

This final stage of healing features tissue remodeling.

Maturation (wound contraction)

100

What are TIMPs?

Tissue inhibitors of MMPs

101

Proper tissue remodeling requires a fine balance of MMPs and _______ to ensure during the wound contraction, we do not destroy ourselves.

TIMPs

102

The influence of location on the rate of healing is largely due to the ___________________.

Relative blood supply to various parts of the body

103

_______ is perhaps the best to regard as the most important cause of impaired wound healing, partly because it is the most common preventable cause of delayed healing.

Infection

104

Why does diabetes mellitus delay wound healing?

Microangiopathy, glucose feeds infectious organisms, makes neutrophils lazy.

105

Why do corticosteroids delay wound healing?

They inhibit TGF-beta production and result in diminished fibrosis. They inhibit protein synthesis in general and collagen synthesis in particular. They are catabolic an wound healing is an anabolic process.

106

How does anemia affect wound healing?

Decreases O2 to site of injury, delaying healing

107

What is dehiscence?

Rupture of a surgical wound or anastomosis.

108

What is a hernia?

The protrusion of a body part somewhere it does not belong. Like your nose protruding into your elbow, in PKU.

109

______________ is caused by excessive creation of ECM, especially of dense collagen, primarily in skin of head, neck and upper chest, primarily in young people after traumatic or thermal injury to deep dermis.

Hypertrophic scarring

110

What are keloids?

Hypertrophic scars that exceed the boundaries of the wound.

111

_________, also called aggressive fibromatosis, is a proliferation of fibroblasts, most common in abdominal wall surgical sites in young adult women.

Desmoid tumor

112

What is wound contracture?

Abnormal excess wound contraction resulting in deformity and impaired movement.

113

Where are contractures particularly common?

Palms (Dupuytren's contracture)
Soles (Lederhosen disease)
Penis (Peyronie Disease)

114

What is fibrosis?

Excessive interstitial collagen deposition, commonly replacing normal functional (parenchymal) tissue.

115

_________ cause the worst fibrosis because the inciting agent is continuously present and cannot be limited or eliminated.

Autoimmune diseases

116

Liver fibroses or scars in a unique way consisting of rounded nodules of regenerating hepatocytes surrounded by fibrous tissue and this unique form of scarring is called:

Cirrhosis

117

What is the major cytokine in fibrosis?

TGF-beta

118

What are cold agglutinins?

Immunoglobulins, predominantly IgM, typically lead to agglutination of erythrocytes below certain temperatures, causing impaired microcirculation and hemolysis.

119

Cold agglutinins are associated with which microbial disease?

Mycoplasma pneumonia

120

A mutinucleated giant cell with nuclei arranged peripherally in a horse-shoe pattern are called:

Langhans type. Associated with immune granulomas. Reacting to infection or autoimmune disease.