Foundations Flashcards Preview

Step 1 > Foundations > Flashcards

Flashcards in Foundations Deck (281):
1

How is the cell cycles regulated?

1. CDKs
2. Cyclins
3. Cyclin-CDK complexes
4. Tumor suppressors

2

What is the shortest phase of the cell cycle

mitosis

3

What are CDKs

they are constitutive and inactive

4

What are cyclins

regulatory proteins that control cell cycle. They are phase specific and activate CDKs

5

What is the importance of cyclin-CDK complexes

must be activated and and inactivated for cell cycle to progress. Inactivated by p21, p27, and p57.

6

What controls p21 activation

p53

7

What tumor suppressors inhibit G1 to S progression

p53 and hypophosphorylated Rb

8

What are the different type of cells

1. permanent
2. stable
3. labile

9

What are examples of permanent cell

Neurons, skeletal/cardiac muscle, RBCs. - remain in Go, regenerate from stem cells

10

What are examples of stable cells

Hepatocytes, lymphocytes. - enter G1 from Go when stimulated

11

What are examples of labile cells

bone marrow, gut epithelium, skin, hair follicles, germ cells. - NEVER go to Go, divide rapidly w/ a short G1

12

What is the role of the Rough ER

1. synthesis of secretory proteins and N-linked oligosaccharide addition to proteins

13

Where in the body are RER found in excess

mucus-secreting goblet cells of small intestine and Ab secreting plasma cells

14

What are Nissl bodies

RER in neurons. They make enzymes and peptide neurotransmitters

15

What is the role of free ribosomes

site of synthesis of cytosolic and organellar proteins

16

What is the role of the SER

steroid synthesis and detoxification of drugs and proteins

17

What cells are rich in SER

liver hepatocytes and steroid hormone producing cells of the adrenal cortex

18

How do proteins get into the nucleus

need to have a nuclear localization signal : 4-8 AA sequence rich in L, R, and Proline

19

What regulates G1 to S phase

1. Cyclin D -- activated CDK4 --> phosphorylates Rb protein which releases it from the TF E2F which transcribes and synthesizes components needed to progress thru S phase
2. Cyclin E - activates CDK2

20

What regulates G2 to M phase

1. Cyclin A - CDK2 complex --> mitotic prophase
2. Cyclin B - CDK1 complex activated by cdc25 = allows breakdown of nuclear envelope and initiation of mitoses

21

What is the role of the Golgi Appartus

1. distribution center for proteins and lipids from the ER to vesicles and plasma membrane
2. Modifies N-oliogosaccharides on asparagine
3. Adds O-oligosaccharides on serine and threonine
4. Adds mannose6-phosphate for trafficking to lyososomes
5. glycosylation of proteins
6. sulfation of sugars and tyrosines

22

What are endosomes

sorting centers for material from outside the cell of from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use

23

What is I cell disease

1. inherited lysosomal storage disease due to failure of addition of mannose 6-phosphate to lysosome proteins.

24

What are the clinical manifestations of I cell disease

1. coarse facial features
2. clouded cornea
3. restricted joint movement
4. high plasma levels of lysosomal enzymes
often fatal in childhood

25

What are the vesicular trafficking proteins?

1. COP I - retrograde
2. COP II - antegrade
3. Clathrin : from trans-Golgi to lysosomes or plasma membrane to endosome (receptor mediated endocytosis)

26

What other proteins are needed for receptor mediated endocytosis

Clathrin, adaptin, and dynamin (plays a role in pinching off the membrane)

27

What is the role of peroxisome?

membrane enclosed organelle invovled in catabolism of very long fatty acids and amino acids.

28

What are the 3 ways protein can be degraded?

1. proteasome
2. lysosomal degradation
3. Ca dependent enzymes

29

What is a proteasome

barrel-shaped protein complex that degrades damaged or unnecessary proteins tagged for destruction w/ ubiqutin

30

What is are microtubules

cyclindrical structure composed of a helical array of polymerized dimers of alpha and beta subunits. They grow slowly and collapse quickly.

31

How many GTP are bound to each dimer

2

32

What uses microtubules

flagella, cilia, mitotic spindles. They also are involved in slow axoplasmic transport in neurons

33

What helps microtubles w/ transported cellular cargo

Molecular motor proteins.
1. Dynenin - retrograde to microtubule
2. Kinesin - anterograde to microtubule

34

What drugs have an effect on microtubules

1. mebendazole/thiabendazole
2. griseofulvin (antifungal)
3. vincristine/blastine
4. paclitaxel
5. colchicine

35

What is Chediak-Higashi Syndrome

mutation in lysosomal trafficking regulator gene whose product is required for the microtubule-dependent sorting of endosomal proteins into late multivesicular endosomes.

36

What are clinical presentations of Chediak-Higashi Syndrome

recurrent pyogenic infections, partial albinism, and peripheral neuropathy

37

Describe the structure of cilia

1. 9+2 arrangement of microtubules.
2. Axonemal dynenin - ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets
3. gap junctions allows cilia to communicated w/ each other

38

What is Kartagener's syndrome

aka Primary Ciliary dyskinesia
1. immotile cilia due to a dynenin arm defect
- male infertility, decreased female fertility, bronchiectasis, recurrent sinusitis, associated w/ situ inversus

39

What are other components of the cytoskeleon

1. actin and mysoin - microvilli, muscle contraction, cytokinesis, adherens junctions
2. intermediate filaments -

40

What is the composition of the plasma membrane

asymmetric lipid bilary. Contains cholesterol and phospholipids As well as sphingolipids, glycolipids, and proteins.

41

What does a high cholesterol content due to the plamsa membrane

decreased fludity, and increases melting temperature

42

What are the various immunohistochemical stains for?
1. Vimentin
2. Desmin
3. Cytokeratin
4. GFAP
5. Neurofilaments
6. Peripherin
7. Nuclear lamins

1. connective tissue - found in sarcomas
2. muscle - rhadomyosarcoma
3. epithelial cells (desmosomes and hemidesmosomes) - carcinomas
4. neuroglia (astrocytes, Schwann cells)
5. axons
6. neurons
7. nuclear envelope and DNA

43

Tell me about the Na-K ATPase pump

3 Na out and 2 K in. During cycle, pump is phosphorylated.

44

What drug can inhibit the NaKATPase

cardiac glycosides (digoxin and digitoxin)
- inhibition of the pump leads to an indirect inhibition of Na/Ca exchange so Ca increases inside the cell --> increasing cardiac contractility

45

What is the most abundant protein in the human body

Collagen

46

Where is type 1 collagen found

BONE, skin, tendon, dentin, fascia, cornea, late wound repair

47

Where is type 2 collagen found

Cartilage (including hyaline), vitreous body, nucleus pulposus

48

Where is type 3 collagen found

Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue

49

What is the type 4 collagen found

basement membrane

50

What cells do collagen synthesis take place in?

fibroblasts

51

What are the steps of collagen synthesis?

1. RER - translation of collagen alpha chains (preprocollagen) -- usually Gly-X-Y (prolin and lysines)
2. Hydroxylation in ER - requires Vit C
3. Glycosylation in ER of hydroxylysine and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chain)
4. exocytosis into extracellular space
5. Cleavage of disulfide rich terminal regions = insoluble tropocollagen
6. Covalent lysine-hydroxylysine cross linkage making collagen fibrils via Cu containing lysyl oxidase

52

What is osteogenesis imperfecta

genetic bone disorder. Most common form is AD w/ abnormal type I collagen. Type II OI - fatal in utero

53

What are the features of the common OI form

1. multiple fractures w/ minimal trauma; may occur during the birth process
2. blue sclerae due to translucency of connective tissue over the choroidal veins
3. hearing loss
4. dental imperfections due to lack of dentin

54

What is Ehlers-Danlos

faulty collagen synthesis during the cross-linking process

55

What are features of Ehlers-Danlos

hyperextensible skin, tendency to bleed, hypermobile joints, berry anuerysms, organ rupture.

56

What are the collagen types affects

1. Type III
2. Type 1 and 5 most frequently in sever classic syndrome

57

What is Alport syndrome

due to a variety of gene defects resulting in abnormal type 4 collagen.
- x-Linked recessive

58

What are the features of Alport syndrome

progressive hereditary nephritis and deafness. may be associated w/ ocular disturbances

59

What is elastin

a stretchy protein w/in skins, lungs, large arteries, elastic ligaments, vocal cords, ligamenta glava.

60

What is the component of elastin

1. rich in proline and glycine - the nonhydroxylated forms
2. topoelastine w/ Fibrillin scaffolding

61

How is elastin degraded

elastase which is normally inhibited by alpha1-antitrypsin. A defect in antitrypsin will lead to excess elastase and panacinar emphysema or liver problems

62

What is Marfan's syndrome

-defect in Fibrillin. Heart problems, tall, long fingers

63

What is apoptosis

programmed cell death, requires ATP. there are two pathways but both ends up activated cytosolic caspases that mediate cellular breakdown. No inflammation is involved with this.

64

what are the histology features of apoptosis

1. cell shrinkage
2. nuclear shrinkage
3. basophilia
4. membrane blebbing
5. nuclear fragmentation (karyorrhexis)
6. formation of apoptotic bodies which are then phagocytosed

65

What can trigger apoptosis

p53, cytokines, cytotoxic T cells, cell stress, absence of GFs

66

What is the intrisinc pathway for apoptosis involved in?

involved in tissue remodeling in embryogenesis, occurs when a GF is withdrawn from a proliferating cell population, also occurs after exposure to injurious stimuli

67

What are the steps for the intrinsic pathway for apoptosis?

1. increase in pro-apoptotic signals : Bax, bak, bcl-x
2. decrease in anti-apptotic signals: Bcl2
3. they increase mitochondrial permeability and cytochrome C is released
4. binds to cytosolic Apaf-1 which activates caspase 9

68

What are the steps for the extrinsic pathway for apoptosis?

1. Ligand receptor interactions: Fas ligands binds to CD95 --> FADD activates caspase 8
2. Immune cells such as killer T cells release perforn and granzyme B

69

What is necrosis?

enzymatic degradation and protein denaturation of a cell resulting from exogenous injury. Intracellular components extravasate and there is an inflammatory process.

70

What are the various types of necrosis?

1. coagulative - heart, liver, kidney
2. liquefactive - brain, bacterial abscess, pleural effusions
3. caseous - TB, systemic fungi
4. Fatty - peripancreatic fat
5. Fibrinoid - blood vessels
6. Gangrenous - dry or wet; common in limbs and in the GIT

71

What type of cell injury is reversible w/ O2?

1. decreased ATP synthesis
2. cellular swelling
3. nuclear chromatin clumping
4. decreased glycogen
5. fatty change
6. ribosomal detachment

72

What type of cell injury is irreversible?

1. nuclear pyknosis, karyolysis, and karyorrhexis
2. Ca influx --> caspase activation
3. plasma membrane damage
4. lysosomal rupture
5. mitochondrial permeability

73

What areas of the following organs are susceptible to ischemia/infarction?
1. heart
2. brain
3. kidney
4. liver
5. colon

1. subendocardium (LV)
2. ACA/MCA/PCA boundary areas
3. straight segment of the PT (medulla), thick ascending limb (medulla)
4. areas around the central vein (zone 3)
5. splenic flexture, rectum

74

Where do red infarcts occur?

loose tissue w/ collaterals such as liver, lungs, or intestines or following reperfusion

75

where do white infarcts occur

solid tissues w/ single blood supply such as heart, kidney, and spleen

76

What are the cell injury byproducts of the following organs?
1. heart
2. skeletal muscle
3. hepatocyte
4. salivary glands
5. pancreas
6. RBCs

1. CK, LDH, troponin
2. CK, aldolase, LDK
3. AST, ALT, alk phos, GGT
4. amylase
5. amylase and lipase
6. LDH, haptoglobin, bilirubin

77

What are the various types of shock?

1. hypovolemic/cardiogenic
2. septic

78

What happens w/ hypovolemic/cardiogenic shock?1

1. low output failure
2. increased TPR
3. low cardiac output
4. cold, clammy patient due to vasoconstriction

79

What happens w/ septic shock?

1. high output failure
2. decreased TPR
3. dilated arterioles and high venous return
4. hot patient due to vasodilation

80

What is atrophy?

reduction in size or number of cells. Decreased metabolic activity b/c of decrease proteins, autophagy, increased protein degradation.

81

What are causes of atrophy?

1. decreased hormones - menopause
2. decreased innervation - motor neuron damage
3. decreased blood flow
4. decreased nutrients
5. increased pressure (nephrolithiasis)
5. occlusion of secretory ducts (CF)

82

What are charactersitics of inflammation?

1. redness
2. pain
3. heat
4. swelling
5. loss of function

83

What happens to the vasculature during inflammation?

increased vascular permeability, vasodilation, and endothelial injury

84

What happens to the cellular component during inflammation?

PMNs extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation, and inflammatory mediator release

85

What are components of acute inflammation?

1. PMNs, eosinophils, Ab mediated
2. Rapid onset, lasts minutes to days
3. outcome = complete resolution, abscess formation, and progression to chronic inflammation
4. IL 1/6/TNFalpha

86

what are components of chronic inflammation?

1. mononuclear cell mediated
2. persistent destruction and repair
3. blood vessel proliferation, fibrosis
4. Granulomas
5. outcomes = scarring and amyloidosis

87

what are granulomas?

nodular collections of epithelioid macrophages and giants cells. Mediated by TNFalpha

88

What are patterns of inflammations?

1. serous - transudate
2. fibrinous - exudate
3. pus

89

What causes cell aging?

1. there is a fixed number of times a cell can divide
2. telomeres - shortened by each round of division
3. telomerases elongate the telomeres. germs cells have a lot of this E. Cancer cells figured out how to activate telomerase
4. restricting caloric intake increases lifespan

90

What is leukocyte extravasation?

neutrophils exit from blood vessels at sites of tissue injury and inflammations

91

What are the steps of leukocyte extravasation?

1. Rolling - mediated by selectins which are increased due to inflammatory cytokines. Sialyl-Lewis on leukocytes bind to selectine
2. Tight Binding - LFA-1 (integrin) on leukocytes bind to ICAM1
3. Diapedesis: leukocytes travel b/w endothelial cells and exits blood vessels. PECAM-1
4. MIgration - cells travel through interstitium to site of injury guided by chemotactic signals.

92

What are some chemotactic signals?

C5a, IL8, LTB4, and Kallikrein

93

What are the various ways that free radicals can damage cells?

1. membrane lipid peroxidation
2. protein modification
3. DNA breakage

94

How is free radical injury initiated?

radiation exposure, metabolism of drugs, redox reaction, NO, transition metals, leukocyte oxidative burst

95

How can free radicals be eliminated?

1. by enzymes - catalase, superoxide dismutase, GSH peroxidase
2. spontaneous decay
3. antioxidants - vitamins A, C, E

96

What pathologies are included w/ free radical injury?

1. retinopathy of prematurity
2. bronchopulmonary dysplasia
3. CCl4, leading to liver necrosis ( fatty change)
4. Acetaminophen overdose (fulminant hepatitis)
5. Fe overload (hemochromatosis)
6. Reperfusion after anoxia especially after thromblytic therapy

97

During wound healing, angiogenesis takes places. What are the 2 ways that angiogenesis can take place?

1. growth of new vessel from preexisting vessel. VEGF, endothelium grows, MMPs modify and create new endothelium and basement membrane
2. VEGF can recruit endothelial progenitor cells to connect up to existing vessel

98

What are the various steps of wound healing?

1. Immediate (0-3 hrs) : clot formation and increased vessel permeability
2. w/in 2 days - neutrophil migration
3. 2-3 days after wound : deposition of granulation tissue and collagen; angiogenesis; epithelial cell proliferation; dissolution of clot; wound contraction mediated by fibroblasts
4. 3-5 days : granulation tissue w/ Type 3 collagen
5. Remodeling: 1 week after wound. Type 3 collagen is replaced by type 1 collagen. Increased tensile strength of tissue. Vit C and Zinc needed for new collagen.

99

What are common granulomatous disease?

1. TB - caseating
2. fungal infxns
3. syphilis - T. pallidum
4. Leprosy - M. Leprae
5. Cat scratch disease - Bartonella Henselae
6. Sarcoidosis
7. Crohn's Disease
8. Wegners
9. Churg- Strauss
10. Berylliosis, silicosis
11. foreign bodies

100

What can happen w/ anti TNF drugs in an granulomatous diease?

TNF-alpha from macrophages induce and maintain granuloma formation. W/ this drugs a side effect can cause sequestering granulomas to breakdown leading to disseminated disease

101

What are the characteristics of a transduate?

1. hypocellular, protein poor
2. low specific gravity < 1.012
3. due to increased hydrostatic pressure, decreased oncotic pressure, and Na retention

102

What are the characteristics of an exudate?

1. cellular, protein rich
2. specific gravity > 1.020
3. Due to lymphatic obstruction and inflammation

103

Where is CRP made?

it's an acute phase reactant made in the liver

104

What is the role of CRP

part of the innate immune system - opsonizes bacteria and activates complement
- can be secreted from atherosclerotic plaques to activate local endothelial cells to induce prothrombotic state to increase adhesions of endothelium leukocytes

105

When is CRP elevated and what can decrease it?

-elevations are strong indicators for MI, stroke, PAD
- lowered by smoking cessation, wt loss, statins, and exercise

106

What is ESR?`

product of inflammation that coats RBCs and causes aggregation. When aggregated the RBCs call at a faster rate within the test tube

107

When do you see increased ESR

1. infections - osteomyelitis
2. inflammation (temporal arteritis)
3. cancer
4. pregnancy
5. SLE

108

When do you see decreased ESR

1. sickle cell
2. polycythemia vera
3. CHF

109

What are some important genes of embryogenesis?

1. Sonic hedgehog gene
2. Wnt7 gene
3. FGF gene
4. Homeobox Gene (hox)

110

Tell me about sonic hedgehog gene

1. produced at base of limbs in zone of polarizing activity
2. anterior to posterior axis
3. CNS development
4. mutation can cause holoprosencephaly

111

Tell me about Wnt-7 gene

1. produced at apical ectodermal ridge
2. necessary for proper organziation along dorsal ventral axis

112

Tell me about FGF gene

1. produced at apical ectodermal ridge
2. stimulates mitosis of underlying mesoderm, providing for lengthening of limbs
3. mutation = short limbs

113

Tell me about Homebox genes

1. segmental organziation of embryo in craniocaudal direction
2. Hox mutations -- appendages in wrong location
3. Vit A - high levels can later Hox gene expression
4. HoxD13 mutation = synpolydactyl

114

What happens w/in wk 1 of fetal development

Day 0 - fertilization
Day 2- zygote
Day 3 - morula at proximal end of fallopian tube
Day 5- Blastocyst.
Day 6- implantation
- hCG secretion begins after implantation of blastocyst

115

What happens w/in wk 2 of fetal developmentb

bilaminar disc
Epiblast
Hypoblast - becomes endodermal yolk sac

116

What happens w/in wk 3 of fetal development

Trilaminar disc - gastrulation
epiblasts becomes the 3 layers
- primitive streak, notochord, mesoderm and its organization, and neural plate begin to form

117

What happens b/w wks 3-8

neural tube forms neuroectoderm and closes by week 4.
- organogenesis
- extremely susceptible to teratogens

118

What happens during wk 4 of fetal development

- heart begins to beat
- upper and lower limbs begin to form

119

What happens at wk 8 of fetal development

- fetal movement, fetus looks like a baby

120

What happens to wk 10 of fetal development

- genitalia have male/female characteristics

121

What is gastrulation

process that forms the trilaminar disc. establishes the ectoderm, mesoderm, and endoderm germ layers. Starts w/ epiblast invaginating to form the primitive streak

122

What comes from the surface ectoderm?

1. adenohypophysis (ant pituitary)
2. lens of eyes
3. epithelial lining of oral cavity, sensory organs of ear, and olfactory epithelium
4. epidermis
5. anal canal below the pectinate line
6. parotid, sweat, and mammary glands

123

What is a crangiopharyngioma?

benign Rathke's pouch tumor w/ cholesterol crystals, calcification

124

What comes from the neuroectoderm?

1. Brain - neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland
2. retina and optic nerve
3. spinal cord

125

What comes from the neural crest cells?

1. PNS - DRG, cranial nerves, celiac ganglion, Schwann cells, ANS
2. melanocytes
3. chromaggin cells of adrenal medulla
4. parafollicular C cells of thyroid
5. pia and arachnoid mater
6. skull of bones and ear
7. odontoblast
8. aorticopulmonary septum
9. Eye - anterior chambe, cornea, sclera, ciliary muscle, iris pigment cells
10. GI - ENS, enterochromaffin cells

126

What comes from the Mesoderm

muscle, bone, CT, serous lining of body cavities, spleen, CV structures, lymphatics, blood, wall of gut tube, wall of bladder, urethra, vagina, kidneys, adrenal cortex, dermis, testes, ovaries

127

What comes from endoderm?

gut tube epithelium - including anal canal above the pectinate line
- luminal epithelial derivatives ( lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)

128

What is agenesis?

absent organ due to absent primordial tissue

129

What is aplasia?

absent organ despite present primordial tissue

130

What is deformation

extrinsic disruption; occurs after the embryonic period

131

What is hypoplasia

incomplete organ development; primordial tissue present

132

What is malformation

intrinsic disruption; occurs during the embryonic period

133

What are common teratogens and what effect due they have?`

1. ACE inhibitors - renal damage
2. Alkylating agents - absence of digits, other problems
3. Aminoglycosides - CN 8 toxicity
4. Carbamazepine - neural tube defects, craniofacial defects, finger nail hypoplasia, developmental delay, IUGR
5. DES - vaginal clear cell adenocarcinoma; congenital Mullerian anomalies
6. Folate antagonists - neural tube defects
7. Lithium - Ebsteins' anomaly - atrialized RV
8. Phenytoin - fetan hydantoin syndrome, microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, mental retardation
9. Tetracyclines - discolored teeth
10. Thalidomide - limb defects
11. Valproate - inhibition of maternal folate absorption --> neural tube defects
12. Warfarin - bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities

134

What are examples of substance abuse affected fetal development?

1. Alcohol - leading cause of birth defects and mental retardation
2. Cocaine - abnormal fetal development and fetal addiction, placental abruption
3. Smoking - preterm labor, placental problems, IUGR, ADHD

135

What are some other causes of fetal developmental problems?

1. Iodide (lack of excess) - congenital goiter or hypothyroidism (cretinism)
2. Maternal diabetes - caudal regression syndrome (anal atresia to sirenomelia), congenital heart defects, neural tube defects
3. Vit A excess - extremely high risk for spontaneous abortions and birth defects (cleft palate, cardia problems)
4. X-rays : microcephaly, mental retardation

136

What is fetal alcohol syndrome?

1. congenital abnormalities- cleft lip/palate
2. mental retardation
3. pre and postnatal developmental retardation
4. microcephaly
5. holoprosencephaly
6. facial abnormalities
7. limb dislocation
8. heart and lung fistulas

137

What makes up the fetal component of the placenta?

1. cytotrophoblasts - inner layer of chorionic villi
2. syncytiotrophoblast - outer layer of chorionic villi, secretes hCG, stimualtes corpus luteum to secrete progesterone during first trimester to maintain endometrium

138

What makes up the maternal component of the placenta?

Decidua basalis - derived from endometrium, Materal blood is in the lacunae.

139

What are all the aortic arch derivatives?

1st Arch - part of maxillary artery (branch of external carotid)
2nd Arch - stapedial artery and hyoid artery
3rd Arch - common carotid artery and proximal part of internal carotid artery
4th Arch - on left (aortic arch); on right (proximal part of right subclavian artery)
6th Arch - proximal part of the pulmonary arteries and ductus arteriosus

140

Where is the right recurrent laryngeal nerve going to loop around?

b/w 3rd and 4th arch

141

Where does the left recurrent laryngeal nerve get caught?

btw 4th and 6th arch due to the ligamentum arteriosum

142

What is the branchial apparatus?

- also called pharyngeal appartus
- made up of branchial clefts, arches, and pouches

143

What are the branchial clefts derived from?

1. ectoderm

144

What are the branchial arches derived from?

mesoderm (muscles, arteries) and neural cresst (bones, cartilage)

145

What are the branchial pouches derived from?

endoderm

146

What are the branchial cleft derivatives?

1st cleft = external auditory meatus
2nd through 4th = temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme
- persistent cervical sinus --> branchial cleft cyst w/in lateral neck -- DOES NOT move w/ swallowing

147

What comes from the 1st branchial arch? think M and T structures

1. Meckel's cartilage: Mandible, Malleus, incus,
Sphenomandibular ligament
2. Muscles of Mastication (Temporalis, masseter, lateral and medial pterygoid)
3. Mylohyoid anterior belly of digastric, tensor tympani, tensor veli palatini

148

What nerves innervate the 1st branchial arch?

CN V2 and V3 - to help w/ chewing

149

What is the Treacher Colins Syndrome?

1st arch neural crest fails to migrate --> mandibular hypoplasia, facial abnormalities

150

What comes from the 2nd branchial arch? think S structures

1. Reichert's cartilage: staphes, styloid process, lesser horn of hyoid, stylohyoid ligament
2. Muscles of facial expression, stapedius, stylohyoid posterior belly of digastric

151

What nerve innervates the 2nd branchial arch/

CN 7 - facial-- think smile

152

What comes from the 3rd branchial arch?

1. Cartilage: greater horn of hyoid
2. Stylopharyngeus

153

What nerve innervates the 3rd branchial arch?

CN 9 - GP - think swallow stylishly

154

What is a congenital pharyngocutaneous fistula?

persistence of cleft and pouch - fistula btw tonsillar area, cleft in lateral neck

155

What comes from the 4 and 6th arches?

1. Cartilage - thyroid, cricoid, arytenoids, corniculate, cuneiform
2. 4th: most pharygneal constrictors, cricothyroid, levator veli palatini
3. 6th : all intrinsic muscles of larynx except cricothyroid

156

What nerves innervate the 4th and 6th arch?

4th: CN 10 - superior laryngeal branch to help w/ swallow
6th: CN 10 - recurrent laryngeal branch to help w/ speaking

157

What branchial arches helps make the posterior 1/3 of tongue?

3 and 4

158

What does the 1st branchial pouch form?

middle ear cavity, eustahcian tube, mastoid air cells
- endodermal lined structures of ear

159

What does the 2nd branchial pouch form?

develops into epithelial lining of palantine tonsil

160

What does the 3rd branchial pouch form?

1. Dorsal wings - inferior parathyroids
2. Ventral wings - thymus

161

What does the 4th branchial pouch form?

Dorsal wings- superior parathyroids

162

What is Digeorge Syndrome?

aberrant development of 3rd and 4th pouches -- T cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid to develop)

163

What mutation is associated w/ Digeorge syndrome?

Ch 22 q11

164

When does a cleft lip form?

failure of fusion of maxillary and medial nasal processes (formation of primary palate)

165

When does a cleft palate form?

failure of fusion of lateral palatine process, the nasal septum, and/or the median palatine process (formation of secondary palate)

166

What is one of the leading causes of fatality from toxicologic agents in kids?

- Fe poisoning

167

What is the mechanism of damage w/ iron poisoning?

cell death due to perodixation of membrane lipids

168

What are the symptoms of iron poisoning?

acute - gastric bleeding
chronic - metabolic acidosis, scarring leading to GI obstruction

169

What is amyloidosis?

abnormal aggregation of proteins or their fragments into Beta-pleated sheet structures leading to cell damage and apoptosis
- affected tissue have a waxy appearance

170

What causes primary amyloidosis?

- AL: deposition of proteins from Ig Light chains
- can occur as plasma cell disorder or associated w/ multiple myeloma

171

What parts of the body are affected w/ primary amyloidosis?

many organs: renal (nephrotic syndrome); cardiac (heart failure, arrhythmia); hematologic (easy bruising); hepatomegaly, and neuropathy

172

What causes secondary amyloidosis?

- seen w/ chronic diseases like RA, IBD, spondyloarthropathy, chronic infxns
- fibrils composed of Serum Amyloid A

173

What amyloid is seen w/ Dialysis-related amyloidosis?

- Beta2 microglobulins in pts w/ ESRD and long term dialysis
- often present as carpal tunnel syndrome and other joint tissues

174

What amyloid is seen w/ heritable amyloidosis?

- heteogeneous group of disorders
- ex: ATTR neurologic/cardia amyloidosis due to transthyretin gene mutation

175

What is seen w/ age-related (senile) systemic amyloidosis?

- deposition of normal (WT) TTR in myocardium and other sites
- slower progression of cardiac dysfunction vs. AL amyloidosis

176

What type of amyloid is seen w/ Alzheimers?

amyloid Beta protein cleaved from amyloid precursor protein (APP)

177

What are the hallmarks of cancer?

1. evasion of apoptosis
2. self-sufficiency in growth signals
3. insensitivity to anti-growth signals
4. sustained angiogenesis
5. limitless replicative potential
6. tissue invasion
7. metastasis

178

What is seen w/ hyperplasia?

- increased number of cells
ex: hormone Estrogen causes breasts to enlarge

179

What is seen w/ dysplasia?

abnormal growth w/ loss of cellular orientation, shape, and size in comparison to normal tissue maturation. Commonly preneoplastic

180

What is seen w/ metaplasia?

one adult cell type is replaced by another
- often secondary to irritation and/or environmental exposure
ex: squamous metaplasia in trachea and bronchii of smokers or intestinal metaplasia in Barrett's esophagus

181

What is seen w/ hypertrophy?

increase in size

182

What are examples of hypertrophy?

1. uterine muscle during pregnancy
2. Chronic HTN - cardiac cells get bigger but makes ventricle stiffer (maladaptive)
3. organelles can hypertrophy as well--> phenobarbitol causes liver SER hypertrophy

183

What is anaplasia?

abnormal cells lacking differentiation, resemble primitive cells of same tissue
- often equated w/ undifferentiated malignant neoplasms. Little or no resemblance to tissue of origin.

184

What -plasia are reversible?

hyperplasia, metaplasia, dysplasia

185

What -plasias are irreversible?

anaplasia, neoplasia, desmoplasia

186

What is neoplasia?

clonal proliferation of cells that is uncontrolled and excessive. May be benign of malignant

187

What is desmoplasia?

fibrous tissue formation in response to neoplasm

188

What is carcinoma in situ?

- neoplastic cells have not invaded basement membrane
- high nuclear/cytoplasmic ratio and clumped chromatin
- neoplastic cells encompass entire thickness

189

How do neoplastic cells invade and metastasize?

- use collagenases and hydrolases (metalloproteinases)
- can metastasize if they reach blood vessel of lymphatics

190

What is grade of a tumor determined by?

degree of cellular differentiation based on histologic appearance
1 = well differentiated, low grade
4 = anaplastic, high grade

191

What is stage of tumor determined by?

- degree of localization/spread based on site and size of primary lesion
- spread to regional lymph nodes
-presence of metastases
- spread of tumor in a specific pt: based on TNM

192

What is an adenoma or papilloma?

benign epithelium neoplasm

193

What do you call a malignant epithelium neoplasm?

adenocarcinoma, papillary carcinoma

194

What is a malignant neoplasm of blood cells?

leukemia and lymphoma

195

What is a benign neoplasm of blood vessels?

Hemangioma

196

What is a malignant neoplasm of blood vessels?

angiosarcoma

197

What is a benign neoplasm of smooth muscle?

leiomyoma

198

What is a malignant neoplasm of smooth muscle?

leiomyosarcoma

199

What is a benign neoplasm of striated muscle? Malignant?

B: rhabdomyoma
M: rhabdomyosarcoma

200

What is a benign neoplasm of connective tissue? malignant?

B: fibroma
M: fibrosarcoma

201

What is a benign neoplasm of bone? Malignant?

B: osteoma
M: osteosarcoma

202

What is a benign neoplasm of fat? Malignant?

B: lipoma
M: liposarcoma

203

What are proangiongenic cytokines?

bFGF and VEGF

204

What does benign neoplasm mean?

usually well differentiated, slow growing, well demarcated, no mets

205

What does malignant neoplasm mean?

may be poorly differentiated, erratic growth, locally invasive/diffuse, may mets

206

What is cachexia?

wt loss, muscle atrophy, and fatigue that occur in chronic dz (cancer, AIDS, heart failure, TB)

207

What cytokines mediate cachexia?

- TNF alpha, IFN gamma, IL6

208

What disease condition is associated w/ ALL and AML?

Down's syndrome

209

What neoplasms are associated w/ xeroderma pigmentosum and albinism?

melanoma, Basal cell carcinoma, SCC of skin

210

What disease condition is associated w/ gastric adenocarcinoma?

- chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants

211

What disease condition is associated w/ SCC of skin?

actinic keratosis

212

What neoplasms are associated w/ tuberous sclerosis (facial angiofibroma, seizures, and mental retardation)?

Giant cell astrocytoma, renal angiomyolipoma, and cardiac rhabdomyosarcoma(!!!)

213

What disease condition is associated esophageal adenocarcinoma?

Barrett's esophagus (GERD)

214

What disease condition is associated w/ SCC of esophagus?

Plummer-Vinson syndrome (decreased iron) and Achalasia

215

What disease condition is associated w/ HCC?

Cirrhosis due to Hep B and C and alcoholic

216

What disease condition is associated w/ colonic adenocarcinoma?

ulcerative colitis

217

What disease condition is associated w/ malignant lymphomas?

immunodeficiency states

218

What neoplasms is Paget's dz of bone associated w/?

Secondary osteosarcoma and fibrosarcoma

219

What disease condition is associated w/ lymphoma?

Autoimmune diseases (Hashimoto's thyroiditis, myasthenia gravis)

220

What neoplasms are associated w/ AIDS?

- aggressive malignant lymphomas and Kaposi's sarcoma

221

What disease condition is associated w/ visceral malignancy (stomach, lung, uterus)?

acanthosis nigricans (hyperpigmentation and epidermal thickening)

222

What disease condition is associated w/ malignant melanoma?

dysplastic nevus

223

What neoplasms is radiation associated w?

leukemia, sarcoma, papillary thyroid cancer, and breast cancer

224

What disease condition is associated w/ B cell lymphoma?

Sjogren's

225

How can tumors arise due to oncogene and TSG dysfunction?

1. Oncogenes - gain of function, only need 1 mutations
2. TSG - loss of function, both alleles must be lost for expression of dz

226

What oncogene is linked w/ CML?

abl - think t9;22 for Y kinase

227

What oncogene is linked w/ Burkitt's lymphoma?

c-myc: transcription factor

228

What oncogene is linked w/ follicular and undifferentiated lymphomas?

bcl-2: anti-apoptotic molecule

229

What oncogene is linked w? breast, ovarian and gastric carcinomas?

HER2/neu (c-erbB2) : Y kinase

230

What oncogene is linked w/ colon carcinoma?

ras - GTPase always on

231

What oncogene is linked w/ lung tumor?

L-myc : transcription factor

232

What oncogene is linked w/ neuroblastoma?

N-myc: transcription factor

233

What oncogene is linked w/ MEN type 2A and 2B?

ret - Y kinase

234

What oncogene is linked w/ GIST?

c-kit: cytokine receptor

235

What TSG is linked w/ Retinoblastoma and osteosarcoma?

Rb : inhibits E2F normally and blocks G1 to S phase

236

What TSG is linked w/ most human cancers and Li-Fraumeni syndrome?

p53: normally a transcription factor for P21 and blcoks G1 to 2 phase as well as G2 to M phase

237

What TSG is linked w/ beast and ovarian canceer?

BRAC1 and 2 - DNA repair proteins

238

What TSG is linked w/ melanoma?

p16 and BRAF

239

What TSG is linked w/ CRC?

APC

240

What TSG is linked w/ Wilm's Tumor?

WT1

241

What TSG is linked w/ Neurofibromatosis type 1? what chromosome?

NF1 on Ch17 - RAS GTPase activating protein

242

What TSG is linked w/ Neurofibromatosis type 2? what chromosome?

NF2 on Ch22 - Merlin (schwannomin) protein

243

What TSG is linked w/ pancreatic cancer?

DPC4

244

What TSG is linked w/ colon cancer?

DCC

245

What is the PSA tumor marker used for?

- follow prostate carcinoma
- can also be elevated in BPH and prostatitis

246

What can also be looked for in prostatic carcinoma besides PSA?

prostatic acid phosphatase

247

What causes increases in CEA levels?

- very nonspecific
- CRC and pancreatic cancers
- gastric, breast, and medullary thyroid carcinomas

248

What causes increases in AFP?

HCC and nonseminomatous germ cell tumors (testis and ovaries)

249

What causes increases in beta-HCG?

pregnancy
- hydatidiform moles and choriocarcinomas

250

What is the marker for ovarian cancer?

CA 125

251

What is S-100 increased in?

melanoma, neural tumors, schwannomas, astrocytomas

252

What is alk phosphatase increased in?

Mets to bones and liver.
- Paget's dz of bone
- Gallstone stuff

253

What is bombesin increased in?

neurblastoma, lung and gastric cancer

254

What is increased in hairy cell leukemia?

- TRAP

255

What is increased in pancreatic adenocarcinoma?

CA19-9

256

What is increased in medullary thyroid carcinoma?

calcitonin - may even cause amyloid deposits

257

What neoplasm is HTLV-1 associated w?

adult T cell leukemia and lymphoma

258

What neoplasm is HBV and HCV associated w?

HCC

259

What neoplasm is EBV associated w?

Burkitt's; Hodgkin's lymphoma; nasopharyngeal carcinoma; CNS lymphoma

260

What neoplasm is HPV associated w?

- cervical carcinoma (16 and 18)
- penile/anal carcinoma
- upper respiratory SCC

261

What neoplasm is HHV-8 associated w?

Kaposi's sarcoma
- body cavity fluid B cell lymphoma

262

What neoplasm is H pylori associated w?

- gastric adenocarcinoma and lymphoma (MALToma)

263

What neoplasm if Schistosoma haematobium associated w?

- SCC of bladder

264

What neoplasm is liver fluke (Clonorchis sinensis) associated w?

- Cholangiocarcinoma

265

What neoplasm is Strep bovis associated w?

- colon cancer

266

What neoplasms do the following chemical carcinogens cause?
1. Aflatoxins
2. Vinyl chloride
3. Carbon tertrachloride
4. Nitrosamines (smoked foods, hot dogs, bologne)
5. Asbestos

1. liver - HCC
2. Liver - angiosarcoma
3. liver - centrilobular necrosis, fatty change
4. stomach - gastric cancer
5. lung - bronchogenic carcinoma and mesohelioma

267

What neoplasms do the following chemical carcinogens causes?
1. Arsenic
2. Naphthalene (aniline) dye - moth balls
3. alkylating agents
4. Benzene
5. Berrylium

1. Skin - SCC; Liver- angiosarcoma
2. Bladder- transitional cell carcinoma
3. Blood - leukemia
4. Blood - leukemia and Hodgkin's lymphoma
5. Hodgkin's lymphoma

268

What neoplasms do the following chemical carcinogens causes?
1. Cadmium
2. Radon
3. Smoking cigs

1. prostate/lung cancer
2. lung cancer
3. Larynx - SCC; Lung - SCC and small cell carcinoma; Kidney - RCC; Bladder- transitional cell carcinoma; Pancreas - adenocarincoma

269

What paraneoplastic syndromes cause hypercalcemia?

- PTHrP due to lung SCC, renal cell carcinoma and breast cancer
- D3 due to Hodgkin's lymphoma and some non-Hogdkin's lymphoma

270

What paraneoplastic syndrome causes SIADH?

ADH from small cell lung carcinoma and intracranial neoplasms

271

What paraneoplastic syndrome causes Cushing's syndrome?

- ACTH or ACTH like peptide from small cell lung carcinoma

272

What paraneoplastic syndromes cause polycythemia?

- EPO from renal cell carcinoma, hemangioblastoma, HCC, and pheochromocytoma

273

What paraneoplastic syndromes cause Lambert-Eaton syndrome?

Abs against presynaptic Ca channels at NMJ due to small cell lung carcinoma

274

What are psammoma bodies?

- laminated concentric calcific spherules

275

What neoplams are psammoma bodies seen in?

- Papillary adenocarcinoma of thyroid
- Serous papillary cystadenocarcinoma of ovary
- meningioma
- malignant mesothelioma

276

What is the cancer epidemiology in men and women?

Men: prostate > lung > colon
Women: breast > lung > colon

277

What is the cancer mortality in men and women?

Men: lung > prostate >colon >pancreas
W: lung > breast > colon > pancreas

278

What neoplasms usually met to the brain?

1. lung
2. breast
3. Genitourinary
4. osteosarcoma
5. melanoma
6. GI

279

What are the symptoms of mets to brain?

headache, seizures, personality changes
- typically see well circumscribed tumors at gray/white matter junction

280

What neoplasms usually met to liver?

1. colon
2. stomach
3. pancreas
4. lung
5. breast

281

What neoplasms usually met to bone?

1. prostate - blastic lesions
2. breast - lytic and blastic lesions
3. lung - lytic lesions
4. thyroid
5. testes