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Pathoma > ch 1 and 2 > Flashcards

ch 1 and 2 Flashcards

1
Q

An increase in stress on an organ leads to…?

A

An increase in organ size by hypertrophy or hyperplasia.

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2
Q

How does hypertrophy occur?

A

Gene activation, protein synthesis, and production of organelles.

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3
Q

How does hyperplasia occur?

A

Production of new cells from stem cells.

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4
Q

Uterus during pregnancy: hypertrophy or hyperplasia?

A

Both, as is generally the case.

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5
Q

What is a permanent tissue? Can they grow? What are the permanent tissues?

A

A tissue that is stable, cannot make new cells. They can only grow by hypertrophy. Skeletal/cardiac muscle and nerve.

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6
Q

How does the heart respond to persistent hypertension?

A

Being a permanent tissue, it grows by hypertrophy.

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7
Q

What is the worry with endometrial hyperplasia? What kind of hyperplasia doesn’t carry this same concern?

A

It (and other pathologic hyperplasias) can progress to dysplasia and eventually cancer. BPH does not increase the risk for cancer.

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8
Q

What are examples of decreases in stress that lead to atrophy?

A

Decreased hormonal stimulation, disuse, or decreased nutrient/blood supply.

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9
Q

How does atrophy occur?

A

Decrease in size and number of cells.

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10
Q

How does the decrease in cell number occur in atrophy?

A

Apoptosis

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11
Q

How does the decrease in cell size occur in atrophy?

A

Ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components.

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12
Q

What is ubiquitin-proteosome degradation?

A

Intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes.

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13
Q

How does autophagy occur in atrophy?

A

Autophagic vacuoles are generated to gobble up cellular components that are no longer needed or sustainable. These vacuoles fuse with lysosomes.

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14
Q

What does a change in stress on an organ lead to?

A

Metaplasia

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15
Q

What is metaplasia?

A

A change in cell type, most commonly involving surface epithelium (changing to a type more suitable to handle the change in stress).

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16
Q

Describe Barrett esophagus?

A

From non-keratinizing stratified squamous (handles friction of food bolus) to non-ciliated columnar with goblet cells (better for handling acid).

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17
Q

How does metaplasia occur?

A

Reprogramming of stem cells.

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18
Q

Is metaplasia reversible?

A

Yes, in theory, with the removal of the stressor.

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19
Q

How do you treat Barrett esophagus?

A

Most importantly, remove the stressor, which is acid reflux. Then, there are therapies to prevent progression to cancer if there’s already dysplasia.

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20
Q

Are we concerned about metaplasia?

A

Only because it can progress to dysplasia and eventually cancer.

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21
Q

Does all metaplasia lead to cancer? exception?

A

No, but there is a definite risk (e.g. Barrett esophagus->adenocarcinoma). Apocrine metaplasia of the breast is the exception. It carries no increased risk for cancer.

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22
Q

What does vitamin A do?

A

It’s necessary for differentiation of specialized epithelial surfaces (e.g. conjunctiva).

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23
Q

What happens when someone becomes vitamin A deficient?

A

They can’t maintain specialized epithelium. For example, the squamous epi of the conjunctiva undergoes metaplasia into stratified stratified keratinizing squamous epithelium. This is keratomalacia.

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24
Q

What is myositis ossificans?

A

Metaplasia in muscle that forms bone during healing after trauma.

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25
Q

What is dysplasia?

A

Disordered cellular growth. Most often refers to proliferation of precancerous cells.

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26
Q

What proliferation is a precursor to cervical cancer?

A

Cervical intraepithelial neoplasia (CIN), which is a dysplastic process.

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27
Q

When does CIN arise?

A

It’s a dysplastic process that arises from longstanding pathologic hyperplasia (e.g. endometrial) or metaplasia (e.g. Barrett).

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28
Q

Is dysplasia reversible?

A

Yes, in theory, with alleviation of the stress. If it persists, however, it progresses to carcinoma, which is irreversible.

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29
Q

What is aplasia? Example?

A

Failure of cell production during embryogenesis (e.g. unilateral renal agenesis).

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30
Q

What is hypoplasia? Example?

A

Decrease in cell production during embryogenesis, resulting in a small organ (e.g. streak ovary in Turner syndrome).

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31
Q

When does cellular injury occur?

A

When a stress exceeds the cell’s ability to adapt.

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32
Q

Which is more susceptible to ischemic injury: neurons or skeletal myocytes?

A

Neurons are highly susceptible, skeletal muscle is more resistant.

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33
Q

How does the rapidity of a stressor affect the response of the cells (e.g. ischemia)?

A

Slowly developing ischemia (e.g. renal artery atherosclerosis), for example, will will to atrophy. Acute ischemia (e.g. renal artery embolus) will result in injury.

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34
Q

What are common causes of cellular injury?

A

Inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.

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35
Q

How does hypoxia cause cellular injury?

A

Oxygen is the final electron acceptor in the ETC of oxidative phosphorylation, so hypoxia hinders ATP production, disabling important cell functions.

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36
Q

What is ischemia?

A

Reduced blood flow through an organ.

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37
Q

When does ischemia arise?

A

Decreased arterial perfusion (e.g. atherosclerosis).Decreased venous drainage (e.g. Budd Chiari)Shock-generalized hypotension resulting in poor tissue perfusion

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38
Q

What is hypoxemia?

A

A low partial pressure of O2 in the blood (i.e. PaO2<60 mm Hg, SaO2<90%).

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39
Q

When does hypoxemia occur?

A

High altitude (decreased PAO2.Hypoventilation (increased PACO2 decreases PAO2).Diffusion defect (e.g. pulmonary fibrosis).V/Q mismatch (circulation e.g. R-L shunt or ventilation prob e.g. atelectasis)

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40
Q

Main causes of hypoxia?

A

Hypoxemia, reduced carrying capacity, and ischemia.

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41
Q

When does decreased O2 carrying capacity arise? Examples?

A

With hemoglobin loss or dysfx. Examples include anemia and CO poisoning.

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42
Q

How does CO poisoning reduce O2 carrying capacity?

A

CO binds Hb much more avidly than O2 does.

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43
Q

What are the PaO2 and SaO2 in anemia? CO poisoning?

A

Both normal.PaO2 normal, SaO2 decreased.

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44
Q

Common exposures to CO?

A

Smoke from fires and exhast from cars or gas heaters (common suicide attempt).

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45
Q

What’s the classic physical finding in CO poisoning? Other findings?

A

Cherry-red appearance of skin. The early sign of expsure is headache. Significant exposure leads to coma and death.

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46
Q

What is methemoglobinemia?

A

When Fe2 is oxidized to Fe3, RBCs can’t bind O2.

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47
Q

PaO2 and SaO2 in methemoglobinemia?

A

PaO2 normal, SaO2 decreased.

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48
Q

When does methemoglobinemia occur?

A

With oxidant stress (e.g. sulfa and nitrate drugs) and in newborns (immature Fe-reducing enzymes).

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49
Q

What’s the classic finding in methemoglobinemia?

A

Chocolate-colored blood.

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50
Q

Tx for methemoglobinemia?

A

Intravenous methylene blue helps reduce Fe3 to Fe2.

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51
Q

What cellular functions does low ATP affect? Consequences?

A

Na-K pumps, resulting in Na/H2O buildup and swelling.Ca pumps, resulting in Ca buildup in cytosol.Aerobic glycolysis, resulting in a switch to anaerobic glycolysis and lactic acid buildup, denaturing proteins and precipitating DNA.

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52
Q

Is cellular injury reversible? What’s the hallmark of reversible injury?

A

It is in the initial phase. The hallmark is cellular swelling.

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53
Q

What histologic findings indicate reversible injury?

A

Loss of microvilli and membrane blebbing indicate cytosol swelling. Dissociation of ribosomes and decreased protein synthesis indicate RER swelling.

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54
Q

What is the hallmark of irreversible cellular injury?

A

Membrane damage.

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55
Q

What are the consequences of specific membranes in the cell being damaged?

A

-Plasma membrane damage results in leakage of cytosolic enzymes into the serum (e.g. cardiac troponin) and addtional Ca entering the cell.-Mitochondrial membrane damage results in loss of ETC (innter mito membrane) and cytochrome c leaking into the cytosol (activates apoptosis)-Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which then become activated by the high intracellular Ca.

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56
Q

What is the morphologic hallmark of cell death? How does it occur?

A

Loss of the nucleus. By condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis).

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57
Q

What are the 2 mechanisms of cell death?

A

Necrosis (murder) and apoptosis (suicide).

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58
Q

Describe the main differences between necrosis and apoptosis?

A

Apoptosis is self-initiated, necrosis is not. Necrosis involves a large group of cells and is followed by acute inflammation. Necrosis is always pathologic, never physiologic.

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59
Q

Describe coagulative necrosis?

A

Necrosis where the organ and cell structures are preserved by coagulation of proteins. The nucleus disappears though. The necrotic tissue remains firm.

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60
Q

When and where does coagulative necrosis occur?

A

Ischemic infarction in any organ but the brain.

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61
Q

How do you recognize an organ that has undergone coagulative necrosis?

A

It will have maintained is shape. The infarcted area is often wedge-shaped and pale.

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62
Q

When does red infarction arise? Examples?

A

When blood re-enters a loosely organized tissue (e.g. an organ that has undergone coagulative necrosis). Examples include testicular and pulmonary infarctions.

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63
Q

What is liquefactive necrosis?

A

Necrotic tissue that becomes liquefied by enzymatic lysis of cells and proteins.

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64
Q

When and where does liquefactive necrosis?

A

Any time an organ is exposed to proteolytic enzymes.It occurs in the brain-enzymes of the microglial cells;in abscesses-enzymes from neutrophils;and in pancreatitis.

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65
Q

When does acute inflammation arise?

A

It is the result of 1. infection and 2. necrosis

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66
Q

What type(s) of necrosis are associated with the pancreas?

A

Fat and liquefactive

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67
Q

What are the types of necrosis?

A

Coagulative, liquefactive, gangrenous, caseous, fat, and fibrinoid.

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68
Q

What is gangrenous necrosis?

A

Coagulative necrosis that resembles mummified tissue (dry gangrene). If superimposed infection of the dead tissue occurs, liquefactive necrosis ensues (wet gangrene).

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69
Q

Where does gangrenous necrosis most often occur?

A

It is characteristic of ischemia of the lower limb and GI tract.

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70
Q

Describe caseous necrotic tissue?

A

Soft and friable, cottage cheese appearance.

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71
Q

When and where does caseous necrosis occur?

A

It is characteristic of granulomatous inflammation due to tuberculous or fungal infection. It’s a combination of coagulative and liquefactive necrosis.

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72
Q

What is fat necrosis?

A

Necrotic adipose tissue with a chalky-white appearance due to the deposition of Ca.

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73
Q

When and where does fat necrosis occur?

A

Trauma to fat (e.g. breast) and pancreatitis-mediated damage of peripancreatic fat. These 2 processes release fatty acids, which then bind Ca in saponification.

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74
Q

What is dystrophic calcification?

A

When Ca deposits on dead tissues.

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75
Q

What does fat necrosis have to do with dystrophic calcification?

A

Saponification is an example of dystrophic calcification (Ca deposits on dead tissue). The necrotic tissue acts as a nidus for calcification.

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76
Q

What are the serum Ca and P levels in dystrophic calcification? metastatic calcification?

A

Ca and P levels are normal. Deposition occurs because there’s a nidus.Ca and P levels are high, leading to deposition throughout the body.

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77
Q

What’s the ddx for Ca deposits in the breast?

A

Carcinoma in situ or fat necrosis.

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78
Q

Why might a patient with fat necrosis think they have breast cancer?

A

The release of fatty acids can sometimes lead to a giant cell reaction, in which the pt might present with a mass consisting of fat, giant cells, and calcification.

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79
Q

What is fibrinoid necrosis?

A

Necrotic damage to the blood vessel wall causes proteins (including fibrin) to leak into the wall.

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80
Q

How do you identify fibrinoid necrosis?

A

It stains bright pink.

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81
Q

When does fibrinoid necrosis occur?

A

Characteristic of malignant hypertension and vasculitis.

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82
Q

What is malignant hypertension?

A

HT that can cause acute damage, like papilledema, hemorrhage, etc. It’s a medical emergency.

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83
Q

What kind of necrosis would pre-eclampsia lead to?

A

Fibrinoid necrosis of the placental vessels.

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84
Q

What is a free radical?

A

A chemical species with unpaired electrons in their outer orbits. They react with and disrupt other stuff.

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85
Q

What is apoptosis?

A

Energy dependent, genetically programmed cell death involving single cells or groups of cells.

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86
Q

Examples of apoptosis?

A

Endometrial shedding during menstruation.Removal of cells during embryogenesis (abscence->e.g. syndactyly).CD8 T cell-mediated killing of virally infected cells.

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87
Q

Describe the morphologic changes in the apoptotic process?

A

As the dying cell shrinks, the cytoplasm becomes more eosinophilic (pink). The nucleus condenses (pyknosis) and fragments (karyorrhexis), and then apoptotic bodies fall (apoptosis means “falling of leaves” in greek) from the cell and are removed by macrophages.

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88
Q

What are the main enzymatic mediators of apoptosis? How do they work?

A

Caspases, which activate proteases and endonucleases.

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89
Q

How are caspases activated?

A

3 pathways:1. Intrinsic mitochondrial pathway2. Extrinsic receptor-ligand pathway3. Cytotoxic CD8 T cell-mediated pathway

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90
Q

What is Bcl2?

A

It stabilizes the mitochondrial membrane, keeping cytochrome c inside.

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91
Q

What events lead to the inactivation of Bcl2? What’s the consequence?

A

Cellular injury, DNA damage, and loss of hormonal stimulation. Inactivation of Bcl2 allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases.

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92
Q

What is the extrinsic receptor-ligand pathway?

A

One of the pathways that can activate caspases and lead to apoptosis. FAS ligand binds FAS death receptor (CD95) on the target cell, activating caspases.Alternatively, TNF binds the TNF receptor on the target cell, activating caspases.

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93
Q

What is the FAS death receptor?

A

CD95 on the target cell.

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94
Q

What is the cytotoxic CD8 T cell-mediated pathway?

A

CD8 T cells secrete perforins, which create pores in the membrane of target cells. They then secrete granzymes, which can enter through the pores and activate caspases. This is how CD8 T cells kill virally infected cells.

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95
Q

When does apoptosis occur in aberrant T cell maturation?

A

Negative selection in the thymus, which assesses whether or not the T cell binds too avidly to self-Ag. If it does, FAS ligand is expressed, binds FAS death receptor, apoptosis.+ selection, on the other hand, tests to make sure that the T cell can properly bind self-Ag on MHC.

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96
Q

What are the 2 ways a cytotoxic T cell kills cells expressing foreign Ag?

A

Fas-induced apoptosis and perforin pathway.

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97
Q

When does physiologic free radical generation occur?

A

Oxidative phosphorylation

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98
Q

What enzyme transfers electrons to O2, the final electron acceptor?

A

Cytochrome c oxidase (complex IV).

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99
Q

What are the free radicals produced in ox phos?

A

O2 + 1 electron=superoxide (O2-)2=hydrogen peroxide (H2O2)3=hydroxyl radical (OH)4=water (H2O)

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100
Q

When does pathologic generation of free radicals arise?

A

Ionizing radiation, inflammation, metals, drugs and chemicals.

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101
Q

How does ionizing radiation generate free radicals?

A

Water is hydrolyzed to hydroxyl free radical

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102
Q

What is the most damaging free radical?

A

Hydroxyl

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103
Q

How does inflammation generate free radicals?

A

NADPH oxidase generates superoxide during oxygen dependent killing by neutrophils.

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104
Q

How do metals create free radicals? What important reaction does this?

A

e.g. copper and iron. Fe2 generates hydroxyl radicals in the Fenton reaction.

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105
Q

How do drugs and chemicals create free radicals?

A

The P450 system can generate free radicals in the process of metabolism (e.g. of acetaminophen).

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106
Q

How do our bodies eliminate free radicals?

A

Antioxidants, enzymes, and metal carrier proteins

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107
Q

What antioxidants do our bodies use?

A

Glutathione, vitamins A, C, E, etc.

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108
Q

What enzymes do our bodies use to eliminate free radicals? How do they work?

A

Superoxide dismutase (mitochondria) converts superoxide to H2O2.Glutathione peroxidase (mitochondria)-GSH+free radical->GSSG and H2OCatalase (peroxisomes) converts H2O2 to O2 and H2O

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109
Q

What are 2 examples of metal carrier proteins that reduce free radical damage?

A

Transferrin and ceruloplasmin

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110
Q

What is the mechanism of tissue damage in hemochromatosis and Wilson dz?

A

Free radical damage

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111
Q

What 2 key features will indicate an apoptotic cell?

A

Small nucleus, pink cytoplasm.

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112
Q

What is CCl4 and what is its significance? What cellular and gross changes will be seen?

A

It’s an organic solvent used in dry cleaning. It’s converted to CCl3 (a free radical) by the P450 system. Results in cell injury with swelling of RER; as ribosomes detach, protein synthesis is impaired. This decreases apolipoprotein production, leading to fatty changes in the liver as fat can’t be mobilized.

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113
Q

How does reperfusion injury work? How will you detect it?

A

As blood returns to ischemic tissue, O2-derived free radicals further damage the tissue.For example, in an MI, cardiac enzymes will rise (e.g. troponin). When you reperfuse (cath), they will continue to rise rather than fall.

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114
Q

What is amyloidosis?

A

Misfolded proteins get deposited in the extracellular space, damaging tissues.

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115
Q

What is amyloid?

A

Any misfolded protein.

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116
Q

What are the shared features among all amyloid?

A

B pleated sheets and congo red staining/apple green birefringence under polarized light.

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117
Q

Where does amyloid deposition occur?

A

Can be systemic or localized.

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118
Q

What is primary amyloidosis? What conditions is it associated with?

A

Systemic deposition of AL amyloid, which is derived from Ig light chain. It’s associated with plasma cell dyscrasias (e.g. multiple myeloma).

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119
Q

What is secondary amyloidosis?

A

Systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA).

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120
Q

What is SAA (serum amyloid associated) protein?

A

An acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean Fever (FMF).

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121
Q

What is Familial Mediterranean Fever? Inheritance? Presentation?

A

FMF is a dysfx of neutrophils that occurs in people of Mediterranean origin. Inheritance is autosomal recessive. It presents with episodes of fever and acute serosal inflammation. There is high SAA during attacks, depositing AA amyloid in tissues.

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122
Q

What dzs can FMF mimic?

A

Appendicitis, arthritis, or myocardial infarction, because of the acute serosal inflammation and fever.

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123
Q

What are the clinical findings in systemic amyloidosis?

A

Nephrotic syndrome, restrictive cardiomyopathy/arrhythmia, tongue enlargement/malabsorption/hepatosplenomegaly.

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124
Q

Which organ is most commonly involved in systemic amyloidosis?

A

The kidney, nephrotic syndrome.

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125
Q

How do you diagnose/tx systemic amyloidosis?

A

Diagnosis requires a tissue biopsy, which can be taken easily from the abdominal fat pad or rectum. Damaged organs must be transplanted, as amyloid cannot be removed.

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126
Q

What are some examples of localized amyloidosis (6 listed)?

A

Senile cardiac amyloidosis, familial amyloid cardiomyopathy, non-insulin-dependent diabetes mellitus, alzheimer dz, dialysis-associated amyloidosis, and medullary carcinoma of the thyroid.

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127
Q

What is senile cardiac amyloidosis? Symptoms? Prevalence?

A

Non-mutated serum transthyretin deposits in the heart. Usually asymptomatic, but is present in 25%>80 yo.

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128
Q

What is familial amyloid cardiomyopathy? Prevalance?

A

Mutated serum transthyretin deposits in the heart, causing restrictive cardiomyopathy. 5% of AAs carry the mutated gene.

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129
Q

How does DM type II cause localized amyloidosis?

A

Amylin is a protein derived from insulin. As the tissues become insulin-resistant, the pancreas pumps out more insulin, and thus more amylin, which then deposits in the islets.

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130
Q

Describe the localized amyloidosis in Alzheimer dz?

A

A-beta amyloid is derived from B-amyloid precursor protein and deposits in the brain, forming amyloid plaques.

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131
Q

Where is the gene for B-APP (beta-amyloid precursor protein) located? Significance?

A

Chromosome 21. Thus, most people with Down Syndrome will develop early-onset Alzheimer dz (usually by age 40).

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132
Q

What is dialysis-associated amyloidosis?

A

B2-microglobulin deposits in the joints.

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133
Q

Why does medullary carcinoma of the thyroid cause amyloidosis? Hallmark of histology?

A

Calcitonin (produced by tumor cells) deposits within the thyroid (“tumor cells in an amyloid background”)

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134
Q

What condition is described as “tumor cells in an amyloid background”?

A

Medullary carcinoma of the thyroid

135
Q

What’s the main difference between acute and chronic inflammation?

A

Acute is mostly neutrophils, chronic is mostly lymphocytes.

136
Q

What is acute inflammation? When does it occur?

A

Edema and neutrophils in response to infection (to eliminate the pathogen) or tissue necrosis (to clear necrotic debris).

137
Q

Acute inflammation: rapidity of response? specificity?

A

Rapid response at the expense of specificity (innate immunity).

138
Q

At what body sites do we see innate immunity?

A

Mostly epithelium and mucous membranes, consisting of the complement system and cells.

139
Q

What are toll-like receptors?

A

TLRs are present on the cells of the innate immune system (e.g. macrophages, dendritic cells) and are activated by pathogen-associated molecular patterns (PAMPs) that are commonly shared by microbes.

140
Q

What TLR on macrophages recognizes what PAMP on gram - bacteria?

A

CD14 recognizes LPS on the outer membrane of gram -s.

141
Q

What happens when a TLR is activated?

A

Upregulation of NFkB, which is a nuclear transcription factor that activates the immune response genes (NFkB is the switch that turns on the immune response by producing a bunch of other immune mediators).

142
Q

Are TLRs present on all both innate and adaptive immune cells?

A

Yes. e.g. macrophages and lymphocytes. Thus, they play a role in both acute and chronic inflammation.

143
Q

What immune factors does cyclooxygenase produce? What do they do?

A

PGs. I2, D2, and E2 mediate vasodilation and increased vascular permeability. E2 also mediates pain.

144
Q

What immune factors does lipoxygenase produce? What do they do?

A

LTs. B4 attracts and activates neutrophils. C4, D4, and E4 mediate vasoconstriction, bronchospasm, and increased vascular permeability (all consequences of smooth muscle contraction; these 3 are the slow reacting substances of anaphylaxis).

145
Q

What are the 2 main mediators of pain?

A

PGE2 and bradykinin.

146
Q

What are the 2 main functions of PGE2?

A

Fever (fEver) and pain.

147
Q

What are the 4 key mediators that attract neutrophils?

A

LTB4, IL-8, C5a, and bacterial products.

148
Q

Where are mast cells located?

A

They are widely distributed throughout CT.

149
Q

What activates mast cells?

A

Tissue trauma, C3a and C5a, or cross-linking of cell-surface IgE by Ag.

150
Q

Describe the response of the mast cell to activation?

A

Immediate response is by release of pre-formed histamine granules, which cause vasodilation and increased vascular permeability.Delayed response involves AA metabolite production, particularly LTs (vasoconstriction, bronchospasm, and increased vascular permeability).

151
Q

What is the complement system?

A

Proinflammatory serum proteins that “complement” inflammation.

152
Q

How is the complement system activated? How does it kill microbes?

A

3 pathways: classical, alternative, and MBL. These pathways lead to the production of C3 convertase, which mediates C3->C3a and C3b. C3 convertase then produces C5 convertase, which mediates C5->C5a and C5b. C5b then complexes with C6-C9 to form the membrane attack complex (MAC).

153
Q

Describe the classical pathway of complement activation?

A

C1 binds IgG or IgM that is bound to Ag. “GM makes classic cars.”

154
Q

Describe the alternative pathway of complement activation?

A

Microbial products directly activate complement.

155
Q

Describe the MBL pathway of complement activation?

A

MBL binds to mannose on microbes and activates complement.

156
Q

What are the anaphylatoxins and what do they do?

A

C3a and C5a trigger mast cell degranulation.

157
Q

What does C5a do?

A

It’s an anaphylatoxin, which means that it causes mast cell degranulation (vasodilation, increased vascular permeability). It also acts as a chemoattractant for neutrophils.

158
Q

What does C3b do?

A

It acts as an opsonin with IgG.

159
Q

What is MAC?

A

Membrane attack complex, formed by C5b and C6-C9. Creates a hole in the cell membrane, leading to cell lysis.

160
Q

What is Hageman factor? What is it’s role in inflammation?

A

Factor VII. It’s an inactive proinflammatory protein produced in the liver. It is activated upon exposure to tissue factor. It then activates the coagulation/fibrinolytic, complement, and kinin systems.Hageman factor is important in DIC, especially in gram - sepsis.

161
Q

Describe the kinin system?

A

Kinin cleaves high molecular weight kininogen (HMWK) to bradykinin, which mediates vasodilation and increased vascular permeability (similar to histamine), as well as pain.

162
Q

What are the cardinal signs of inflammation?

A

Rubor, calor, dolor, tumor.

163
Q

What causes rubor and calor? Key mediators?

A

Redness and warmth are from increased blood flow (vasodilation). Key mediators are histamine, PGs, and bradykinin.

164
Q

What causes tumor (swelling)? Key mediators?

A

Leakage of fluid from post-capillary venules into the interstitial space (exudate). Key mediators are histamine (endothelial cell contraction) and tissue damage (endothelial cell disruption).

165
Q

What causes dolor? Key mediators?

A

Pain is mediated by PGE2 and bradykinin, which sensitize sensory nerve endings.

166
Q

How do you distinguish acute from chronic inflammation histologically?

A

Look for neutrophils and lymphocytes. Neutrophils are multi-lobated. Lymphocytes are not, and plasma cells have peripherally displaced nuclei with a slight clearing adjacent to them.

167
Q

What causes fever?

A

Pyrogens (e.g. LPS) cause macrophages to release IL-1 and TNF, which increase COX activity in perivascular cells of the hypothalamus. This increases PGE2 production, raising the temperature set point.

168
Q

What are the steps of neutrophil arrival and fx?

A
  1. Margination2. Rolling3. Adhesion4. Transmigration and chemotaxis5. Phagocytosis6. Destruction of phagocytosed material7. Resolution
169
Q

What is margination (leukocytes)?

A

When you get vessel dilation, leukocytes spend more time at the vessel wall because of the slowed and more turbulent flow.

170
Q

How does rolling occur (leukocytes)?

A

P-selectin release from Weibel-Palade bodies is mediated by histamine. E-selectin is induced by TNF and IL-1. Selectins bind sialyl Lewis X on leukocytes, allowing these “speed bumps” to perform their fx.

171
Q

How does adhesion occur (leukocyte)?

A

Cellular adhesion molecules (ICAM and VCAM) are upregulated on endothelium by TNF and IL-1. Integrins are upregulated on leukocytes by C5a and LTB4. Interaction between CAMs and integrins results in firm adhesion.

172
Q

What surface are selectins expressed on? integrins? CAMs? sialyl Lewis X?

A

Selectins and CAMs on endothelium. Sialyl Lewis X and integrins on leukocytes.

173
Q

What is leukocyte adhesion deficiency?

A

LAD is the inability to adhere, most commonly due to an autosomal recessive integrin defect (CD18).

174
Q

What are the clinical features of LAD?

A

Delayed umbilical separation, recurrent bacterial infections that lack pus, and increased circulating neutrophils (the marginated pool joins the ranks but can’t migrate because they can’t adhere).

175
Q

How do transmigration and chemotaxis occur?

A

Once adherence occurs, the neutrophils just follow chemotactic factors, including bacterial products, IL-8, LTB4, and C5a. They transmigrate across the endothelium of postcapillary venules.

176
Q

What is phagocytosis?

A

Consumption of pathogens or necrotic tissue.

177
Q

What factors can enhance phagocytosis?

A

Opsonins, IgG and C3b.

178
Q

How does phagocytosis occur?

A

Pseudopods extend from leukocytes to form phagosomes, which are internalized and merge with lysosomes to produce phagolysosomes.

179
Q

What are the 3 stages of acute inflammation?

A

Fluid (brings serum and its factors in), Neutrophil (peaks around 24 hr), and Macrophage (peaks around 2-3 days).

180
Q

What are the 2 main factors released from Weibel Palade bodies?

A

Think of the P(P-selectin) and the W(von Willebrand factor).

181
Q

Where’s the marginated pool of neutrophils?

A

The vessels of the lungs.

182
Q

What’s the benefit of opsonins?

A

They enhance the phagocytic process, and thy also make it a more specific process, as phagocytosis can be pretty non-specific.

183
Q

What is Cheiak-Higashi syndrome?

A

A protein trafficking (microtubule) defect, characterized by impaired phagolysosome formation.

184
Q

What’s the inheritance pattern of Chediak-Higashi syndrome?

A

Autosomal recessive

185
Q

Clinical features of Chediak-Higashi syndrome?

A

Recurrent pyogenic infections, neutropenia (intramedullary death of neutrophils), giant granules in leukocytes (they can’t be evenly distributed via microtubules), defective primary hemostasis (due to abnormal dense granules in platelets), albinism, and peripheral neuropathy (impaired axonal transport).All these things are related to impaired railroad fx.

186
Q

Why does Chediak Higashi syndrome cause albinism?

A

With the defective microtubule transport, melanocytes can’t transport their melanin to the neighboring keratinocytes.

187
Q

What are the 2 mechanisms of phagocytosis? Which is most effective?

A

O2-dependent (most effective) and independent.

188
Q

What is the oxidative burst? Describe the process?

A

The purpose is to produce HOCl in the phagolysosomes. The oxidative burst is where O2 is converted to superoxide by NADPH oxidase. Superoxide is converted to H2O2 by superoxide dismutase (SOD), and H2O2 is converted to HOCl by myeloperoxidase (MPO).

189
Q

What is chronic granulomatous dz?

A

Poor O2-dependent killing because of an NADPH oxidase defect.

190
Q

Inheritance pattern of chronic granulomatous dz?

A

X-linked or autosomal recessive.

191
Q

Cinical pattern of CGD?

A

Recurrent infection with catalase + organisms.

192
Q

What are the main organisms that cause infection in CGD?

A

Catalase + orgs, particularly S. aureus, Pseudomonas cepacia, Serratia marcescens, Nocardia, and Aspergillus.

193
Q

How do you screen for CGD?

A

Nitroblue tetrazolium test. When leukocytes are incubated with NBT dye, they turn blue if they can convert O2 to superoxide with NADPH oxidase. If it’s defective, it won’t turn blue.

194
Q

What does MPO deficiency do?

A

You can’t convert H2O2 to HOCl, increasing the risk for Candida infections, though most pts are asymptomatic.

195
Q

Can you detect MPO deficiency with NBT test?

A

No, it will be normal, as it has a normal oxidative burst.

196
Q

What is O2-independent killing?

A

Enzymes in secondary granules do the killing. It’s less effective than O2-dependent killing.

197
Q

What enzymes are in the secondary granules of leakocytes?

A

Lysozyme in macrophages, major basic protein in eosinophils.

198
Q

Describe resolution of a pyogenic infection?

A

Neutrophils undergo apoptosis and disappear within 24 hours after resolution of the inflammatory stimulus.

199
Q

Why do catalase + organisms cause infection in chronic granulomatous dz?

A

Leukocytes need superoxide to kill pathogens. If there’s an NADPH oxidase defect, we can’t produce H2O2 properly. However, we can usually borrow H2O2 from the pathogens and convert it to HOCl by MPO. Catalase + organisms degrade H2O2, leaving you vulnerable to infection without H2O2 and HOCl.

200
Q

When do neutrophils peak after inflammation begins? Macrophages?

A

24 hrs. 2-3 days.

201
Q

Where do monocytes become macrophages?

A

Monocytes circulate and enter the tissue, where they become macrophages.

202
Q

How do macrophages enter the tissue in inflammation?

A

Same as other leukocytes (margination, rolling, adhesion, transmigration, chemotaxis, phagocytosis).

203
Q

How do macrophages kill pathogens?

A

Enzymes (e.g. lysozyme) in secondary granules (O2 independent killing).

204
Q

What anti-inflammatory cytokines are produced by macrophages to start to shut down the inflammatory process in resolution?

A

IL-10, TGF-B, etc.

205
Q

What produces IL-10 and TGF-B?

A

Macrophages

206
Q

What cell is the “manager” of inflammation?

A

Macrophages assesses the work of the neutrophils and declares whether more work needs to be done. If not, it initiates resolution and healing.

207
Q

What is continued acute inflammation?

A

Inflammation with persistent pus formation. IL-8 from macrophages recruits additional neutrophils.

208
Q

What is an abscess?

A

Acute inflammation surrounded by fibrosis, which is mediated by macrophages via fibrogenic growth factors and cytokines.

209
Q

What is chronic inflammation?

A

Long-standing inflammation where macrophages present Ag to activate CD4 helper T cells, which secrete cytokines that promote chronic inflammation. Characterized by lymphocytes and plasma cells in tissue. It’s a delayed response but is more specific than acute inflammation.

210
Q

What are the stimuli for chronic inflammation?

A

Persistent infection (MCC); infection with viruses, parasites, fungi; autoimmune dz; foreiggn material; and some cancers.

211
Q

What the most common cause of chronic inflammation?

A

Persistent infection.

212
Q

At what stage are T cells released from the bone marrow?

A

As progenitor T cells

213
Q

What happens to T cells in the thymus?

A

They further mature. The T cell receptor (TCR) undergoes rearrangement and progenitor cells become CD4 helper cells or CD8 cytotoxic T cells.

214
Q

Can T cells recognize Ag not on MHC?

A

For the most part, no.

215
Q

What makes up the TCR complex?

A

TCR (T cell receptor) and CD3. Used for Ag surveillance.

216
Q

What MHC molecules do CD4 cells use? CD8?

A

CD4 use MHC class II. CD8 use MHC class I.

217
Q

How are T cells activated?

A

Binding of Ag/MHC complex and an additional 2nd signal.

218
Q

What’s the 2nd signal for CD4 helper T cell activation?

A

B7 on APC binds CD28 on the T cells.

219
Q

What cytokinds do Th1 T cells secrete and why?

A

IL-2 is a T cell growth factor and activator. IFN-g is a macrophage activator.

220
Q

What does IL-2 do?

A

It’s a T cell growth factor and activator.

221
Q

What is IFN-g?

A

Macrophage activator secreted by Th1 cells.

222
Q

What cytokines do Th2 cells secrete?

A

IL-4 (facilitates B cell class switching to IgG and IgE), IL-5 (eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA), and IL-10 (inhibits Th1 phenotype).

223
Q

What is IL-4?

A

Secreted by Th2 cells, facilitates B cell class switching to IgG and IgE.

224
Q

What is IL-5?

A

Secreted by Th2 cells, acts as an eosinophil chemotactic factor and activator, matures B cells to plasma cells, and class switching to IgA.

225
Q

What is IL-10?

A

Secreted by Th2, inhibits Th1.

226
Q

What expresses MHC class I?

A

All nucleated cells and platelets.

227
Q

How does B cell activation occur?

A
  1. Ag binding by surface IgM or IgD->maturation to IgM or IgD secreting plasma cells.or2. B cell Ag presentation to CD4 helpter T cells via MHC class II leads to secretion of cytokines that activate B cells.
228
Q

Describe how helper T cells activate B cells?

A

B cells present Ag to CD4 T cells via MHC class II and the CD40 receptor on B cells bind CD40L on helper T cells, providing the 2nd activation signal. The helper T cell then secretes IL-4 and IL-5 (B cell isotype switching, hypermutation, and maturation to plasma cells).

229
Q

What is the 2nd signal for B cell activation?

A

CD40 on the B cell binds CD40L on the helper T cell.

230
Q

What cytokines do helper T cells secrete to activate B cells?

A

IL-4 and IL-5.

231
Q

What’s the 2nd signal for CD8 T cell activation?

A

IL-2 from CD4 Th1 cell provides the 2nd signal.

232
Q

How do cytotoxic CD8 T cells kill?

A

By the secretion of perforin or granzyme or by the expression of FasL, which binds Fas on target cells. These both activate apoptosis.

233
Q

What’s the defining, key feature of granulomas?

A

Epithelioid histiocytes.

234
Q

What does a granuloma look like?

A

It’s a collection of epithelioid histiocytes (macrophages with abundant pink cytoplasm), usually surrounded by giant cells and a rim of lymphocytes.

235
Q

What are the 2 broad categories of chronic inflammation?

A

Granulomatous and non-granulomatous.

236
Q

What are the 2 categories of granulomatous inflammation?

A

Caseating and non-caseating

237
Q

Describe caseating granulomatous inflammation?

A

Central necrosis (cells lack nuclei) and is characteristic of tuberculosis and fungal infections.

238
Q

Describe non-caseating granulomatous inflammation?

A

Lacks central necrosis. Common etiologies include reaction to foreign material, sarcoidosis, beryllium exposure, Chron dz, and cat scratch dz.

239
Q

What dz is associated with stellate-shaped granulomas?

A

Cat scratch dz

240
Q

What’s the hallmark lesion in Chron dz? UC?

A

Non-caseating granulomas. Crypt abscesses.

241
Q

What stains do you use to determine the etiology of a caseating granuloma?

A

AFB stain detects TB, while a GMS (silver) stain detects fungus.

242
Q

What are the steps involved in granuloma formation?

A

Macrophages present Ag to CD4 T cells. Macrophages then secrete IL-12, which induces CD4 cells to differentiate into the Th1 subtype, which secrete IFN-g, which convertes macrohpages to epithelioid histiocytes and giant cells.

243
Q

Summarize the steps in the formation of a granuloma?

A

Macrophages present Ag to CD4 T cell. Macros secrete IL-12, which causes T cells to become Th1 type and secrete IFN-g, which cause macros to become epithelioid histiocytes and giant cells.

244
Q

What are the primary immunodeficiencies?

A

Digeorge syndrome, SCID, X-linked agammaglobulinemia, CVID, IgA deficiency, hyper IgM syndrome, Wiskott Aldrich syndrome, and complement deficiencies.

245
Q

What is digeorge syndrome?

A

Failure of the development of the 3rd and 4th pharyngeal pouches to form due to a 22q11 microdeletion. Presents with symptoms from the lack of structuresn normally formed by those pouches: T cell deficiency (no thymus), hypocalcemia (no parathyroids), and abnormalities of the heart, great vessels, and face.

246
Q

What’s the genetic basis of digeorge syndrome?

A

22q11 microdeletion.

247
Q

Which syndrome involves a microdeletion at 22q11?

A

Digeorge syndrome

248
Q

What is SCID?

A

Defective cell-mediated and humoral immunity.

249
Q

What are the etiologies of SCID?

A

Cytokine receptor defects, Adenosine deaminase (ADA) deficiency, and MHC class II deficiency.

250
Q

How do cytokine receptor defects cause SCID?

A

Because cytokine signaling is necessary for B and T cell maturation.

251
Q

How does adenosine deaminase deficiency lead to SCID?

A

ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of these is toxic to lymphocytes.

252
Q

What is the most important etiology of SCID?

A

ADA deficiency. Adenosine and deoxyadenosine can’t be excreted and are toxic to lymphocytes.

253
Q

What infections is a SCID pt susceptible to?

A

Fungal, viral, bacterial, and protozoal, including opportunistic infections and live vaccines.

254
Q

Tx for SCID?

A

Sterile isolation (‘bubble baby’) and stem cell transplantation.

255
Q

What is X-linked agammaglobulinemia? whats the mutation?

A

Complete lack of Ig due to disordered B cell maturation (pre and pro B cells can’t mature to naive B cells due to mutated Bruton tyrosine kinase.

256
Q

How does X-linked agammaglobulinemia present?

A

After 6 months with recurrent bacterial, enterovirus (e.g. polio and coxsackie), and Giardia lamblia infections. Live vaccines must be avoided.

257
Q

What is common variable immunodeficiency? Susceptibility?

A

CVID is low immunoglobulin due to B or helper T cell defects. Susceptible to bacterial, enterovirus, and Giardia lamblia infections, usually in late childhood. Also carries an increased risk for autoimmune dz and lymphoma.

258
Q

What dzs are associated with CVID?

A

Autoimmune dz and lymphoma.

259
Q

What is IgA deficiency? Susceptibility?

A

Low serum and mucosal IgA. Most common immunoglobulin deficiency. Increased risk for mucosal infection, especially viral. Most are asymptomatic.

260
Q

What’s the most common Ig deficiency?

A

IgA deficiency.

261
Q

How do most pts with IgA deficiency present?

A

Most are asymptomatic, but may have recurrent mucosal (esp viral) infections.

262
Q

What dz is associated with IgA deficiency?

A

Celiac dz

263
Q

What is hyper-IgM syndrome?

A

Elevated IgM due to mutated CD40L (on helper T cells) or CD40 (on B cells). The 2nd activation signal can’t be delivered to helper T cells during B cell activation, so class switching doesn’t occur.

264
Q

What’s the presentation of hyper-IgM syndrome?

A

Because class switching doesn’t occur, there’s elevated IgM with low levels of IgA, IgG, and IgE, resulting in recurrent pyogenic infections (poor opsonization), especially at mucosal sites.

265
Q

Characterize Wiskott Aldrich syndrome?

A

Characterized by thrombocytopenia (petechiae in skin and mucosal membranes), eczema, and recurrent infections due to mutation in the WASP gene.

266
Q

What gene is implicated in Wiskott Aldrich syndrome? Inheritance pattern?

A

WASP gene. X-linked.

267
Q

What parts of the immune system are defective in Wiskott Aldrich syndrome?

A

Humoral and cellular

268
Q

What do C5-C9 deficiencies set you up for?

A

Neisseria infection (N gonorrhea and N meningitidis)

269
Q

Presentation of C1 inhibitor deficiency?

A

Hereditary angioedema or skin and mucosal surfaces because C1 inhibitor controls C1 activation. Thus, a deficiency leads to hyperactivation of the complement system.

270
Q

What happens when self-reactive lymphocytes develop?

A

They don’t pass negative selection and undergo apoptosis in the thymus (T cells) or bone marrow (B cells), or they become anergic.

271
Q

What is anergy?

A

When lymphocytes are self-reactive, they can become anergic (if they don’t undergo apoptosis), due to recognition of the Ag in peripheral lymphoid tissues with no 2nd signal.

272
Q

How does SLE damage ocur?

A

An autoimmune dz with Ab that damage several host tissues via type II (cytotoxic) and type III (Ag-Ab complex) hypersensitivity.

273
Q

Who has the highest rates of lupus?

A

Women, especially AA females.

274
Q

What are the clinical features of lupus?

A

Fever and weight lossMalar ‘butterfly’ rash (especially on exposure to sunlight)ArthritisPleuritis and pericarditis (involvement of serosal surfaces)CNS psychosisRenal damageEndocarditis, myocarditis, or pericarditisAnemia, thrombocytopenia, or leukopenia

275
Q

What is the most common renal damage in lupus?

A

Diffuse proliferative glomerulonephritis is most common, though others occur.

276
Q

What layer of the heart is affected in lupus?

A

Any and all layers can be affected.

277
Q

What classic endocardial lesion is found in lupus?

A

Libman-Sacks endocarditis is characterized by small, sterile deposits on both sides of the mitral valve.

278
Q

What causes anemia, thrombocytopenia, and leukopenia in lupus?

A

Ab against cell surface proteins.

279
Q

What are the most common causes of death in lupus?

A

Renal failure and infection

280
Q

How do you diagnose SLE?

A

Antinuclear antibody (ANA) are sensitive but not specific. Anti-dsDNA Ab are highly specific and are used to confirm the dx.

281
Q

What finding is characteristic of drug-induced SLE?

A

Antihistone Ab

282
Q

What are common causes of drug-induced SLE? tx?

A

Hydralazine, procainamide, and isoniazid. Removal of the drug usually leads to remission.

283
Q

What finding in SLE is associated with thrombosis?

A

Antiphospholipid Ab syndrome is found in 30% of SLE cases. These autoAb are against proteins bound to phospholipids. These result in arterial and venous thrombosis, including deep venous thrombosis, hepativ vein thrombosis, and stroke.

284
Q

What finding can suggest placental thrombosis?

A

Recurrent pregnancy loss

285
Q

What are the most common Ab in antiphospholipid Ab syndrome?

A

Anticardiolipin and lupus anticoagulant.

286
Q

What tests do antiphospholipid Abs affect?

A

They lead to falsely elevated PTT studies and false + syphilis tests.

287
Q

tx for antiphospholipid Ab syndrome?

A

Lifelong anticoagulation

288
Q

What is Sjogren syndrome?

A

Autoimmune destruction of lacrimal and salivary glands.

289
Q

Describe the autoimmune mechanism of damage in Sjogren syndrome?

A

Lymphocyte-mediated (type IV hypersensitivity) with fibrosis.

290
Q

What’s the classic presentation of Sjogren syndrome?

A

Dry eyes (keratoconjunctivitis), dry mouth (xerostomia), and recurrent dental caries in an older woman (50-60 yo).

291
Q

What dz classically presents with “can’t chew a cracker, dirt in my eyes”?

A

Sjogren syndrome

292
Q

Lab findings in Sjogren syndrome?

A

ANA and anti-ribonucleoprotein Ab (anti-SS-A/Ro and anti-SS-B/La).

293
Q

What’s the target of anti-SSA and SSB Ab in Sjogren syndrome?

A

ribonucleoproteins

294
Q

What other dzs are associated with Sjogren syndrome?

A

Other autoimmune dz, especially RA. Also, increased risk for B cell (marginal zone) lymphoma.

295
Q

What would you think if a pt with confirmed Sjogren syndrome presents with unilateral enlargement of the parotid gland?

A

B cell (marginal zone) lymphoma, which usually occurs late in the dz course.

296
Q

What is scleroderma?

A

Autoimmune damage with activation of fibroblasts and deposition of collagen (fibrosis).

297
Q

What are the 2 types of scleroderma?

A

Diffuse and localized.

298
Q

Diffuse-type scleroderma: organs involved? Presentation? Lab findings?

A

Almost any organ can be involved, but the esophagus is most commonly affected, in which case disordered motility occurs and the pt might complain of dysphagia for solids and liquids. Characterized by ANA and anti-DNA topoisomerase (Scl-70) Ab.

299
Q

Localized type scleroderma: organs involved?

A

Local skin and late visceral involvement. The prototype is CREST syndrome. Calcinosis/anti-Centromere Ab, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasis of the skin.

300
Q

What is Mixed Connective Tissue dz?

A

An autoimmune dz of proximal muscles with mixed features of SLE, systemic sclerosis, and polymyositis. Pt might complain of difficulty combing hair or walking up stairs. Characterized by serum Ab against U1 ribonucleoprotein.

301
Q

Regeneration vs. repair?

A

Regeneration is replacement of damaged tissue with native tissue, which is ideal but not always possible. Repair is replacement with a fibrous scar.

302
Q

What are the 3 types of tissues (based on regenerative capacity)?

A

Labile, stable, and permanent

303
Q

What are the labile tissues and where are their stem cells?

A

Small and large bowel (stem cells in mucosal crypts), skin (stem cells in the basal layer) and bone marrow (hematopoietic stem cells).

304
Q

What stage of the cell cycle are the cells in in stable tissues?

A

Go (quiescent), but can reenter the cell cycle to regenerate tissue when necessary.

305
Q

What is the classic example of stable tissue?

A

The liver, which undergoes compensatory hyperplasia after partial resection. Each hepatocyte produces additional cells and then reenters quiescence.

306
Q

What are the main permanent tissues?

A

Myocardium, skeletal muscle, and neurons all lack significant regenerative potential.

307
Q

When does tissue repair (as opposed to regeneration) occur?

A

When regenerative stem cells are lost (e.g. deep skin cut) or when a tissue lacks regenerative capacity (e.g. post-MI).

308
Q

What happens in the initial phase of repair?

A

Granulation tissue forms.

309
Q

What is granulation tissue made of?

A

Consists of fibroblasts (deposit type III collagen), capillaries (provides nutrients), and myofibroblasts (contract wound).

310
Q

How does granulation tissue become scar tissue?

A

Type III collagen is replaced with type I collagen.

311
Q

What type of collagen is in cartilage?

A

Type Ii (cartwolage).

312
Q

Describe type III collagen?

A

Pliable, present in granulation tissue, embryonic tissue, uterus, and keloids.

313
Q

Describe type I collagen?

A

high tensile strength, present in skin, bone, tendons, and most organs.

314
Q

What removes type III collagen in scar formation?

A

Collagenase, which requires zinc as a cofactor.

315
Q

How do tissue and regeneration occur?

A

Paracrine signaling via growth factors (e.g. macrophages secrete growth factors that target fibroblasts), which then interact with receptors (e.g. epidermal growth factor with growth factor receptor) and result in gene expression and cellular growth.

316
Q

What are examples of mediators of tissue repair and regeneration?

A

TGF-a is an epithelial and fibroblast GFTGF-B is an important fibroblast GF; also inhibits inflammationPDGF is a GF for endothelium, smooth muscle, and fibroblastsFibroblast GF is important for angiogenesis and mediates skeletal developmentVEGF is important for angiogenesis

317
Q

What growth factor is an apithelial and fibroblast GF?

A

TGF-a

318
Q

What growth factor is an important fibroblast GF and inhibits inflammation?

A

TGF-B

319
Q

What growth factor is for endothelium, smooth muscle, and fibroblasts?

A

PDGF

320
Q

What growth factor is for angiogenesis and also mediates skeletal muscle development?

A

Fibroblast GF

321
Q

What growth factor is important in angiogenesis?

A

VEGF

322
Q

What is primary intention?

A

Healing where the wound edges are brought together (e.g. suturing) and leads to minimal scar formation.

323
Q

What is secondary intention?

A

Edges of wound are not approximated. Granulation tissue fills the defect and myofibroblasts then contract the wound, forming a scar.

324
Q

When is wound healing delayed?

A

Infection, vitamin C/copper/zinc deficiency, foreign body, ischemia, diabetes, and malnutrition.

325
Q

What’s the most common offender in wound healing delay due to infection?

A

S. aureus

326
Q

Why is vitamin C important in wound healing?

A

It’s a cofactor in the hydroxylation of proline and lysine procollagen residues, which is a necessary step in collagen cross-linking (allows procollagen to be strengthened).

327
Q

Why is copper important in wound healing?

A

Cofactor for lysyl oxidase, which cross-links lysine and hydroxylysine to form stable collagen.

328
Q

Why is zinc important in wound healing?

A

Cofactor for collagenase, which replaces type III of granulation tissue with stronger type I collagen.

329
Q

What is dehiscence?

A

Rupture of a wound; most commonly seen after abdominal surgery.

330
Q

What is a hypertrophic scar?

A

Excess production of scar tissue that is localized to the wound.

331
Q

What is keloid?

A

Excess production of scar tissue that is out of the proportion to the wound (leaves the normal boundaries).

332
Q

What type of collagen characterizes granulation tissue?

A

Type III

333
Q

Who gets keloid?

A

Mostly AAs

334
Q

What parts of the body classically form keloid?

A

Earlobes, face, and upper extremities.

Pathoma (2 decks)

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