Exam 1 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Name of Dr. Rubinstein’s Puppy

A

Legend

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What embryonic derivatives does epithelium come from

A

All 3. Ectoderm, mesoderm, endoderm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What type of epithelium lines the small intestine

A

simple columnar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the three types of endocytosis

A
  1. Phagocytosis - ingestion of large particles into phagosomes.
  2. Receptor-mediated endocytosis
  3. Fluid phase endocytosis (pinocytosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the two types of exocytosis

A
  1. Regulated exocytosis - signal before the secretory vesicles fuse with the membrane.
  2. Constituitive secretion - secretory vesicles continuously fuse with the plasma membrane.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Names of the 2 surfaces of an epithelial cell

A

Apical (top), basal (bottom)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Types of transport through an epithelium (2 types)

A

Transcellular (larger molecules, through the cell)

Paracellular (between cells, smaller, and regulated by tight junctions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What causes Cystic Fibrosis

A

apical Cl chanels do not open, disrupting polarity in epithelium and thickening the mucous layer covering the epithelia.

Protein is misfolded and never makes it to the cell membrane, it is retained in the ER.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is in the basement membrane

A

The basal lamina (top layer, known as lamina densa), which contains laminin, fibronectin, type IV collagen, proteoglycans

The reticular lamina (lower) which contains type III collagen (reticular fibers)

lamina lucida is the top layer, which contains adhesive glycoproteins (integrins) - links to anchor proteins at hemidesmosomes and focal adhesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the adhesive proteins that link the basal lamina to anchor proteins on the epithelial cell at hemidesmosomes and focal adhesions

A

Integrins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do microvilli do and what are they made of

A

increase surface area, contain a core of actin filaments that attach to the terminal web, where they interact with horizontal actin filaments. Villin anchors actin filaments in the tip. Actin and myosin interact at the terminal web to form a contractive matrix, causing the microvilli to spread.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are sterocillia (villi), what do they do, and where are they found

A

Epididymis, proximal part of ductus deference, and sesory cells of the innear ear. Actin filament core, interconnected by cytoplasmic bridges.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are motile cilia (true cilia), and what do they do

A

Have a 9+2 pattern of microtubules, dynein is motor protein by splitting ATP, has synchronous movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Monocilia

A

Have a 9+0 arrangement of microtubule pairs, they are immotile cilia that can function as mechanoreceptors that respond to fluid displacement, may create left-right assymetry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the types of glands and what do they do

A

Endocrine - no duct - secreted dirrectly into connective tissue and diffuses into blood

Exocrine - duct system

Unicellular (goblet cell containing mucinogen, a hydrophilic glycoprotein)

Multicellular

Simple (single duct) or compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are actin filaments and what do they do

A

Form core of microvilli, provide cell motility by polymerizing, form contractile ring for cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are intermediate filaments and what do they do

A

Stable tissue specific, maintain cell integrity by linking to intercellular junctions (so cells do not rupture when stretched). They do not change length, and make up keratins, vimentin, neurofilaments, and lamins. They attach to desmosomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are microtubules and what do they do

A

Treadmill by maintaining a constant length while polymerizing and depolymerizing. Polarize the organelles, form mitotic spindle and core of cilia. They move using kinesin and dynein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Zonula Occludens (Tight Junction)

A

Semipermeable barrier between apical and basolateral membranes, Linked to actin filaments in the terminal web by claudin/occludin. Tight junction membranes are linked by the cadherins occludin and claudin that are bound to several classes of ZO proteins that are linked to actin.

Can seal of the apical surface of the cell from the basal and lateral borders, so that cell polarity is possible.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Zonula adherens

A

lower than the zonula occludens. Linked to actin filaments in the terminal web by cadherins. Cadherins are calcium dependent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Desmosome (Macula adherens)

A

Anchors intermediate filademtns, linked by cadherins (desmocollins and desmogleins).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Gap Junctions

A

Form connexon channels that permit cell to cell communication. No link to anchor proteins, allow free flow of ions and messengers between cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Hemidesmosome

A

Links cells to matrix, uses integrins linked to intermediate filaments. Use integrins instead of cadherins for adhesive proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Focal Adhesions

A

Links cells to matrix, using integrins linked to actin microfilaments. Molecular basis for cell migration. Integrins connect to fibronectin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Explain the secretory pathway in a cell

A

Begins at RER, vesicular transport to the Golgi apparatus, vesicular transport either directly to the cell surface or into secretory vesicles, with these then moving to the cell surface upon a signaling event.

The Golgi complex distributes everything

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Why does RER stain blue in H&E

A

abundant, negatively charged mRNA associated with it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do proteins get to the ER

A

membrane and secretory proteins have signal sequences, that are recognized by Signal Recognition Particles (SRPs). They stop translationand bind to a docking protein in t he RER, where the SRP falls off and translation continues.

Any protein without a signal sequence is moved to the cytoplasm.

Proteins that stay inthe ER have retention signals, interacting with receptors in the ER that prevent them from leaving.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Functions of the ER

A

Protein folding (possible toxic gain of function by aggregation, Parkinsons, Alzheimers), glycosylation (addition of carbohydrate), sorting, quality control, degredation, and integrating responses to cellular stresses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How is protein folding accomplished

A

folding enzymes

molecular chaperones that bind to newly made proteins and stop them from aggregating. As the protein folds, chaperone binding sites are hidden.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Chaperones as clinical targets

A

In parkinsons, there is aggregation of proteins, so if more chaperone can be introduced and overexpressed, it can cause the mutated protein to fold correctly more often

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Drugs that correct folding defects

A

Read-through editors: read through premature stop codon

Correctors - help to fold the protein properly

Potentiators - improve the function of the misfolded protein after it is made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

ER-Associated Degredation

A

Misfolded protein complexed with ubiquitin is transported out of the ER, where it is degraded by the proteosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Things that cause accumulationof unfolded proteins

A

hypoxia, glucose deprivation, calcium abberations, viral infection, cancers (chaperone limited), misfolding mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How to proteins get to the Golgi

A

Transport vesicles bud from the ER, moving on microtubules to the Golgi where they fuse with the cisternae.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Functions of the Golgi apparatus

A

Glycosylation (adding carbohydrates), Lipid biosynthesis, proteolytic processing, secretion and sorting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How does the Golgi make lysosomal enzymes, and what happens when it goes wrong

A

A mannose 6 phosphate is added, allowing them to go to lysosomes. In lysosomal storage diseases, enzymes are secreted because this M6P is not added.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Signaling for secretory granules to fuse with the membrane

A

Signal causes an influx of calcium, leading to massive degraulation and release of contents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is vesicle/membrane fusion catalyzed by

A

SNARE proteins, one on the vesicle (vSNARE), one on the target membrane (tSNARE)

Botox cleaves SNARE proteins, preventing neurotransmitter release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

General structure of the endocytic system

A

Early endosomes are mildly acidic, here they either recycle to the cell surface or deliver contents to more acidic late endosomes, late endosomes (site of mebrane degredation MVB) send material to lysosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

High Cholesterol caused by failure of endocytosis

A

LDL cannot bind to a cell receptor with a mutation and is not endocytosed. Therefore, LDL is present in blood at a high level.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

H&E Staining

A

Hematoxylin is a basic stain and stains strong acid containing material blue

Eosin is an acidic stain and stains basic substances (such as proteins) red

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Endothelium vs. mesothelium

A

Endothelium lines blood vessels, mesothelium lines body cavities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

simple Squamous Epithelia and where they are found

A

thin, nucleus bulging out into the lumen. Found in alveoli of the lung

found in mesothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Simple cuboidal epithelia and where they are found

A

tall and wide, found in liver, endocrine and exocrine glands, and kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

simple columnar epithelia and where they are found

A

tall, in endocrine and exocrine glands, lining of intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

stratified squamous epithelia and where they are found

A

basal layer is cuboidal, top layer squamous. Found in skin, digestive tract, vagina.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Stratified cuboidal epithelia and where they are found

A

Rare. found in larger ducts of some exocrine glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

stratified and pseudostratified columnar epithelia and where they are found

A

stratified - anorectal region, very large exocrine ducts

psuedo - tall cells that span whole membrane and short that do not. Lines the trachea, bronchi, and ducts of epididymis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Transitional epithelium and where it is found

A

Accomodates strethcing, lines bladder, ureter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Fibronectin

A

binds basal lamina components to integrins on the cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the darkly staining line near the surface of epithelial cells

A

The terminal web, and array of actin filaments that connects to the actin in the microvilli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Names and order of junctions found at the apicolateral border of the cell

A
  1. zonula occludens
  2. zonula adherens (belt desmosomes)
  3. macula adherens (spot desmosomes, desmosomes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Calcium Influx and Gap Junctions

A

Causes gap junctions to close immediately, so neighboring cells cannot be damaged.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Progenitor cells

A

Transit amplifying, arise from stem cells and divide rapidly to produce daughter cells tha differentiate to generate and maintain tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Totipotent vs. pluripotent vs. multipotent

A

toti: zygote, can make all tissues, including placenta
pluri: all embryonic tissues, not placenta

multipotent - can make multiple cell types in tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

2 types of stem cell asymmetry

A

divisional asymmetry - “stemness” factor only into one daughter cell

environmental asymmetry - nice provides signals that help stem cells retain self-renewal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

HSC’s

A

Hematopoetic stem cells, in bone marrow, are very rare and hard to identify

In the current view, Long term reconstituting cells devide into short term reconstituting cells. These STR’s become a common myeloid (everything other than immune) progenitor or a common lymphoid progenitor.

Label-retaining cells are called stem cells

Localize to the endosteal region of the bone marrow, must stay in this niche to retain potency, can migrate in blood to other niches (because of this we can take bone marrow from blood)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

How are stem cells separated out

A

Flow cytometry techniques that separate cells based on flourescently labeled antibodies, followed by fluorescence activated cell sorting, or FACS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

MSC’s

A

Mesenchymal stem cells - multipotent cells derived from many tissues. CAn be injected into the blood stream, and they will migrate to places where we know stem cells exist. They adhere to plastic and have a few markers that are notable.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Induced pluripotent stem cells and their problems

A

convert differentiated fibroblasts into ES-like cells taht are self-renewing and pluripotent. However, this may promote cancer development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Cancer and Stem Cells

A

only a small number of cancer cells are capable of producing a new tumor

Could be from transformation of a normal SC through mutation - rare

activation of self-renawal pathways in already cancerous cells

Shown by AML-causing oncogene injected in mice, cell’s gain self-renewal. This self-renewal correlates with gene expression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Ki67 antigen

A

expressed at all phases of active cell cycle but not in G0 in resting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Cell Cycle restriction point

A

G1-S boundary. If GF’s are withdrawn before this cells do not divide. However, having passed this the cell is committed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

pRB

A

protoypical tumor suppressor protein in retinoblastoma. Rb encodes this protein. It represses E2F transctipion factors (inhibited when bound to pRB). Kinases phosphorylate pRB, and it releases E2F.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

CDK

A

Cyclin dependent kinase complexes. These regulate pRB through phosphorylation, and are activated by cyclins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Cyclin/CDK complexes

A

These regulate different stages of the cell cycle. Cyclin D/CDK4/6 and cyclin E.CDK2 pushes cells to the restriction point by hyperphosphorylating pRB.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

CDK2 vs. CDK4/6

A

CDK2 is a much better kinase than CDK4/6 and hyperphosphorylates pRB after it is slighlty phosphorylated by 4/6.

pRB remains hyperphosphorylated until the end of mitoses, and is dephosphorylated by phosphatases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

CKI (INK4)

A

(Inhibitors of CDK4) inhibits cyclin/CDK activity in response to cell stresses

loss leads to cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

p16INK4a gene

A

often lost or silenced in cancer cells

causes protective cell cycle arrest in melanomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

features of Apoptosis

A

Highly ordered, ATP dependent, proteases and nucleases destroy cell, puts everything in vesicles.

Distinct from necrosis, that is cell lysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Two layers of skin

A

Epidermis - stratified squamous, keratinized

dermis - connective tissue containing vessels, glands, nerve endings, roots)

Below this there is the superficial fascia, loose connective tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Layers of the epidermins and their properties

A

Stratum basale

Stratum spinosum

Stratum granulosum

stratum lucidum

stratum corneum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

stratum basale

A

cuboidal or columnar, divide frequently. All cells attached to basement membrance by hemidemsosomes.

keratin 5 and 14 proteins that dimerize to form intermediate filaments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

stratum spinosum

A

intercellular spindle bridges attached by desmosomes, extensive intermediate filaments. Membrane-coating granules, or lamellar bodies, spinosum cells produce keratins 1 and 10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

stratum granulosum

A

flattened nucleated keratinocytes multilayeed, keratohyalin granules that make the cells dark.

Synthesizes filaggrin, which induces keratin aggregation

Has many lamellar bodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Stratum lucidum

A

Nucleus not visible, dead cells (only in thick epidermis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

stratum corneum

A

keratin filaments crosslinked with fillabgin. Complex of lipids from lamellar bodies cross links the cell envelope and is highly resistant to degredation. Moist surfaces don’t have a stratum corneum.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Two layers of the dermis

A

papillary layer (superficial, loose connective tissue)

Reticular layer (ticker and less cellular, Langer’s lines of tension are formed here)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Attachment of epidermis to dermis

A

dermal papillae are fingerlike projections from the epidermis into the dermis

Basal side: Anchoring fibrils extend from the basal lamina to the collagen (reticular) fibrils of the connective tissue.

Epithelial side: laminin, collagen XVII, and integrins adhese the basal lamina and there are hemidesomsomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Four classes of cutaneous mechanoreceptors

A

Merkel corpuscles, Meissner corpuscles, Pacnian corpuscles, and hair receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Pacnian corpuscle

A

Looks like an onion, central region has nerve process. Found near the junction of the dermis and the hypodermis.

Respond to pressure and vibration and are tickle receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Meissner’s corpuscles

A

smaller than pacnian, found in dermal papillae especially in fingertips.

Respond to light touch. Fingers, toes, lips

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Langerhan’s cells

A

Antigen-presenting cells in skin, between keratinocytes, leave the skin and move to lymphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

melanocytes

A

melanosome organelles rpduce melanin. Located between the basal and spinosum layers. melanin is secreted in the interstitial space and is taken up by keratinocytes.

Derviced from neural crest tissue. UV stimulated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Merkel cells

A

mechanoreceptors in stratum basale, linked to keratinocytes by desomosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

KLK’s

A

Cleave desmosomes in a pH dependent manner. Inhibited at high pH of the bodly, but at lower pH surface of skin) Corneal cells are shed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

constitutive receptor activity

A

some receptors stay in the R(a) form instead of the R(i) form even in the absence of ligand binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

5 transmembrane signaling mechanism

A
  1. diffuse across membrane (steroid) and act on intracellular receptor
  2. receptor spans domain, signal binds to EC domain and activates enzymatic activity in the cytoplasmic domain (cytokine receptors)
  3. Signal binds to EC domain which activates a tyrosine kinase on cyto side
  4. ion channel opened by signal
  5. G-protein coupled receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

steroid receptor mechanism

A

bind to a protein that releases repressors (like HSP90, heat shock) when the steroid is bound, activates dNA transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

cytokine receptors

A

dimerize when activated, then activate separate mobile protein (JAK) molecules, which phosphorylates signal transducers and activates STAT molecules

(Growth hormone, erythropoietin, interferon)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Stat molecule

A

Signal Transducer and Activation of Transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

receptor tyrosine kinase

A

dimerizes and the cytoplasmic domains become phosphorylated, and they catalyze phorphorylation of substrate proteins

(EGF, PDGF, TGFB, insulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Ligand Ion Channel

A

several subunits, ligand binds to site on one of the subunits (neurotransmitters)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

structure and activity of G proteins

A

Have alpha, beta, gamma conformation

dissociate into alpha and beta-gamma

uses binding and hydrolysis of GTP, and ampifies the signal to another protein (usually cAMP

95
Q

Histamine and epinephrine and G proteins

A

epinephrine dilation, histamine constriction, in constant opposition

96
Q

Regulation of the GPCR response

A

phosphorylation of the receptor weakens sensitivity by Gprotein coupled receptor kinases (GRK’s) - recruits B arrestin

Can either recycle the receptor and remove the arrestin, or degrade the receptor

97
Q

Ras signaling

A

Initiated by RTK’s (EGFR binding), dimerization of tyrosine residues phosphorylates the receptor, and two proteins connect like legos to inactive rass, which gets rid of GDP and allows GTP to bind (higher conc. in cell)

Ras is a G protein. It has self GTPase activity as a molecular switch, can hydrolyze its own GTP to turn off.

Ras phosphorylates other things.

98
Q

Ras and cancer

A

mutation abolishes Ras GTPase activity so it can’t shut itself off

30% of human cancers have ras mutations

Activating mutaitons in EGFR for Raf (activated by ras) are uncontrolled in cancer

99
Q

melanomas and the ras pathway

A

50% of melanomas have activating mutations in B-Raf (right downstream of ras), vemurafenib inhibits this form of B-raf and leaves normal raf alone

However, acquired resistance in some tumor cells show restored ras pathway inactivation, even in the presence of vemurafenib

It does this by activating other Raf proteins (we have more than one) in oncogene bypass

RESTORE OR BYPASS

100
Q

prefixes: fibro, chondro, osteo
suffixes: blast, cyte

A

fibro: connective
chondro: cartilage
osteo: bone
blast: young and active
cyte: old and tired

101
Q

Loose irregular connective tissue

A

cell types are transient, primarily present benaty the epithelia that lines the body surfaces, and tracts. Surrounds vessels and nerves as well.

Structural element is type 1 collagen

102
Q

Type 1 collagen

A

Found in most connective tissue, 90% of all body collagen. Viscous, resistance to stretching

103
Q

Dense irregular connective tissue

A

abundant fibers, little ground substance. Present where stresses are high, such as skin. Hollow organs covered by this.

Structural element also type 1 collagen

104
Q

Dense regular connective tissue

A

tendons, ligaments in bundles, or alternating parallel perperdicular sheets in cornea or bone.

105
Q

Two types of connective tissue cells and examples

A

resident cells: fibroblasts, chondrocytes, osteocytes, adipocytes (all derived from connective tissue stem cell) Mast cells and macerophages are also regarded as long term resident alien cells, as they arise from bone marrow precursors.

transient cells: neutrophils, eosinophils, basophils, monosytes, immune cells.

106
Q

fibroblast

A

principal cell of connective tissue, makes collagen, elastic fibers, reticular fibers, and carbohydrates of ground substance.

Stellate with long processes and spindle nuclei. Less active fibroblasts are fibrocytes.

107
Q

myofibroblast

A

same lineage as fibroblasts, contain actin and myosin thick filaments, allowing for contraction in injuries

108
Q

chondroblasts and chondrocytes

A

produce type II collagen in cartilage

109
Q

osteoblasts and osteocytes

A

produce the type I collagen in bone, along with other bone ECM

110
Q

white fat vs. brown fat

A

white fat is an adipobyte containing a single large fat vacuole. Brown fat has many small vacuoles and uncoupled mitochondria (UCP-1 protein)

111
Q

Macrophages

A

phagocytize particles (put them in phagosomes), derived from monocytes. Can also serve as antigen presenting cells.

oval with round nuclei, have many lysosomes as well as RER, golgi, and mitochondria

112
Q

mast cells

A

chemical mediators in connective tissue, have many granules containing things such as histamine. IgE binds and the exocytotic event begins.

Oval shaped with round nuclei

113
Q

Type II collagen

A

dominant collagen in hyaline and elastic cartilage, resistant to compression

114
Q

Type III collagen

A

forms reticular fibers, found in blood vessel walls. Loose network of thin fibers, smaller than collagen I.

Found in spleen, thymus, lymph nodes

115
Q

Type IV collagen

A

major component of basal and external lamina, assembles into mesh instead of fibrils (unlike other collagen), partly due to interruptions in helical structure and interweaving with laminin. Support and filtration barrier

116
Q

Steps in collagen synthesis (up to cell excretion)

A

type 1 colalgen in RER facors coiling of an alpha chain of collagen into a tight helix. 3 alpha chains are wounding into a triple helix, and then there is crosslinking of the component alpha chains by disulfide and hydrogen bonds. This resulting triple helix is procollagen. They are assembled into secretory vesibles and secreted into the extracellular space.

117
Q

collagen formation (post-procollagen secretion)

A

staggered head to tail procollagen molecules line up in side to side arrays to form fibrils of collagen, with covalent cross linking.

118
Q

Reticular fibers

A

Thin collagen fibers are coated with glycoproteins. Composed of type III collagen. In the spleen and lymph nodes, the reticular cell synthesizes this type III collagen.

119
Q

Elastic fibers

A

major component is elastin, initially synthesized as a soluble precursor molecule. Elastin molecules form random coils instead of helicies.

Found in the vertebral column and in arteries

120
Q

Three groups of ground substances

A
  1. Glycosaminoglycan molecules (GAGS)
  2. Proteoglycans
  3. multiadhesive glycoproteins
121
Q

GAG’s

A

Glycosaminoglycan molecules, covalently bound to proteoglycans, long, unbranched dissacharide chains, witha high negative charge. Gives tissue turgor.

122
Q

proteoglycans

A

large macromolecules made of core protein and GAGs. form gels with water, giving tissues rugor. Can also be binding for signal molecules

proteoglycan monomers attach to a backdone of hyaluronan to form proteoglycan aggregates

123
Q

multiadhesive glycoproteins

A

stabilize the ECM, fibronectin and laminin are examples of these, posses binding sites for ECM proteins

124
Q

cause of Osteogenesis Imperfecta

A

mutation of one of two genes coding for alpha chains in type I collagen

125
Q

Ehlers-Danlos syndrome

A

skin hyperextensibility, defect in a gene coding for alpha chains in Type V collagen

126
Q

Alport syndrome

A

abnormally permeable kidneys

defect in type IV collagen, major component of basal lamina

127
Q

Marfan syndrome

A

long extremities, dilated aorta, dislocated lenses

defect in gibrillin 1, resulting in disrupted elastic fiber formation

128
Q

Scurvy

A

vitamin C deficiency state. lack of hydroxalyation of proline and lysine in collagen. These stabilize collagen

129
Q

What type of collagen fibers form the basal lamina? The reticular lamina?

A

Basal: type IV

Reticular: type III

130
Q

Is blood considered a tissue?

A

Yes

131
Q

Difference between plasma (non RBC component of blood) and serum

A

Serum has lost clotting factors, they are in the blood cell portion

132
Q

Major proteins found in plasma

A

Fibrinogen (synthesized in the liver, help clotting)

Albumin (75% of all protein)

Globulins (antibodies)

133
Q

albumin

A

75% of all protein in plasma, major contributor to osmotic pressure that maintains intravascular volume

binds bilirubin, fatty acids, drugs, metals

134
Q

Erythrocytes

A

Rich in ribosomes during infancy (reticulocytes)

33% hemoglobin in RBC’s

Cytoskeletal network of spectrin and actin, ankyrin makes connection, prevents shear

135
Q

Elliptocytosis

A

Defects in elastin, RBCs cannot “bounce back”

136
Q

spherocytosis

A

defects in spectrin and ankyrin, lose membrane steadily (blebbing) and become smaller and lose biconcave shape

137
Q

platelets

A

have an active cytoskeleton, integrin receptors that can bind to fibronectin, cause a liquid to turn into a gel

138
Q

2 types of leukocytes

A

myeloid cells and lymphocytes

(leukocytes are White Blood Cells)

139
Q

3 types of granulocytes

A

basophil, neutrophil, eosinophil

140
Q

Neutrophils

A

Very inactive chromatin, nucleus constricted in different regions connected by thin strands of chromatin, short living, major phagocytic cells

granules contain toxic substances, such as myeloperoxidase

Most frequent WBC, much more than basophil and eosinophil

141
Q

Eosinophils

A

Release cytokins and granule cells into EC space in response to cytokines

Role in antiviral and antibacterial, defend aganinst parasites

Contain MBP (Major Basic Protein), eosinophil peroxidase, eosinophil cationic protein (ECP) and Eosinophil-derived neurotoxin (EDN)

142
Q

Basophils

A

Express IgE receptors, host defense, play a role in allergy, have extremely dense and dark staining granules

143
Q

Monocytes

A

precursor cells of the mononuclear phagocytic system, become macrophages

kidney shaped nucleus

express different scavenger receptors on the surface to recognize pathogens

144
Q

Gaucher’s disease

A

lysosomal deficiency, cell can’t break down damaged blood cells

Give macrophages a ruffled appearance because they cannot break down the dead material

145
Q

Lymphocytes

A

B cells (precursors to plasma cells and memory cells, produce and secrete antibody)

T cells (help make antibody, destroy abnormal cells)

NK cells (destroy abnormal cells)

B and T cells are histologically unremarkable

NK cells are larger with visible granules

146
Q

Regulated motility and adhesion are critical to leukocyte function

A

Selectins, chemoattractants, and integrits cause diapedisis, tissues displacy selectins when they want the cell to come to its surface

actin nucleation and brancing

147
Q

diapedesis

A

transendothelial migration by leukocytes

148
Q

actin nucleation and branching

A

GTPases drive a treadmilling process, acting as molecular switches

149
Q

Wiskott-Aldrich syndrome

A

failure to stimulate actin polymerization, neutrophils are deficient in phagocytosis, T cells do not polarize

150
Q

Two types of hematopoesis

A

Primitive (embryonic) - 5-10 times the size of mature erythrocyte, occurs in the yolk sac in blood islands, these then migrate to the liver, which is chief at 3 months.

Definitive (adult), occurs in bone marrow (medullary hematopoiesis, between the sinuses in the marrow stroma) and within the liver and spleen (in conditions of stress), (extramedullary hematopoesis)

151
Q

Colony stimulating factors

A

regulators of hematopoiesis

152
Q

myeloproliferative disorders

A

JAK2 (Janus Kinase 2) mediates the EPO signals, mutation causes it to phosphorylate STAT5 without EPO, abnormal RBC production called polycythemia vera

153
Q

CFU

A

Colony forming unit - monocytes and granulocytes derive from a common precursor

154
Q

5 stages of myelopoesis and their forms for granulocytes

A

myoblast (large, euchromatic nucleus)

promyelocyte (large nuclei, granules start)

myelocyte (3 types can be distinguished based on granules, nucleus starts to become indented, last time that mitosis can happen)

metamyelocyte (smaller nucleus, clear granules)

band cell (nucleus is horseshoe shaped, cytoplasm similar to mature form)

155
Q

How long do neutrophils last in the circulation

A

about 24 hours, most time is spent in the bone marrow before this

156
Q

Erythropoeisis

A

Basophilic erythroblast: Deep blue cytoplasm due to ribosomes

polychromatic erythroblast - transcription slowing, starts to be eosinophilic due to proteino

orthochromatic erythroblast - nucleus pushed to one side, cytoplasm eosinophilic

reticulocyte - nucleus extruded

157
Q

Megakaryocytes

A

Sit near vascular channels, protrude through the sinusoids, blood shear force stimulates the cell to form bulbs and pinch off to form platelets

158
Q

Suffix for deficiency of a cell in the peripheral blood

A

-penia

159
Q

suffixes for excess of cells

A
  • cytosis
  • philia
  • emia
160
Q

Bohr Effect

A

Conformational change in Hb that releases oxygen into the hypoxic tissue

161
Q

What do the secondary granules of eosinophils contain

A

MBP (Major Basic Protein) and peroxidase

162
Q

Monocytes and inflammatory response

A

exit a blood vessel at the site of inflammation, transform into a macrophage. Chemotax toward factors such as N-formyl peptides

163
Q

APC

A

antigen-presenting cell

164
Q

What elements do platelets release

A

serotonin and thromboplastin, released by granules

165
Q

Glanzmann’s thrombasthenia

A

severe reduction in platelet aggregation mutation in integrin so it can no longer bind to fibrinogen

166
Q

Structure of bone marrow

A

nutrient arteries enter through bone foramina. They give rise to sinusoids (thin walled vessels in the endosteum. Sinusoids are oriented in a radial direction, downs the central longitudinal vein in the long axis of the bone. Hematopoetic cells are between the sinuses

167
Q

Walls of the sinusoids

A

endothelial cell layer, basement membrane, and a reticular cell layer (adventitial cells). These adventitial cells create microenvironments in the marrow that nurture specific hematopoetic lineages.

Reticular cells can become adipose cells (yellow bone marrow, found in adults)

168
Q

GATA1 protein

A

needed for the maturation of red blood cells, but also is active at earlier steps in the hemopoietic pathway

169
Q

Thrombopoetin

A

Tpo stimulates the proliferation of the megakaryoblast

170
Q

How do eosinophils and basophils moderate each other

A

Basophils release chemotactic agents that attract eosinophils, which neutralize histamine and produce a factor that inhibits degranulation, neutralizing the effect.

171
Q

How do the mature cells leave the marrow and enter the blood

A

push against the endothelial cells and push through the aperture into the sinusoids

172
Q

Fick’s Law of Diffusion

A

Quantity diffused per time. Net diffusive moemnt is the sum of two opposing unidirectional movements.

Diffusion time varies with the square of the distance.

Proportionality factor is the permeabiity of the compound

173
Q

Permeability of substances

A

With the excpetion of water, permeability is related to the lipid solubility

174
Q

Facilitated diffusion

A

Protein spans the membrane and the molecule moves through the protein. However, facilitated diffusion is limited by the number of proteins

175
Q

Osmotic pressure

A

hydrostatic pressure required to prevent net water flow

176
Q

van’t Hoff formula

A

Relationship between osmotic pressure and solute concentration. Doesn’t take much solute to get water to move.

177
Q

Hyperkalemia

A

too much extracellular K+. abnormal heart rhythms

178
Q

Ion concentrations of Na+, K+, Ca2+, and Cl- in the ECF and ICF

A

Na - 145mM ECF, 15mM ICF

K - 4.5 mM ECF, 120 mM ICF

Ca - 1mM ECF, 100nM ICF

Cl - 120 mM ECF, 6mM ICF

High Na and Ca outside, High K inside

179
Q

3 professors who went to med school together

A

Ochs, Rubinstein, and Goldman

180
Q

Donnan equilibrium

A

System where all ions except for one (typically large anions) are allowed to passively diffuse until they reach equilibrium

181
Q

Goldman-Hodgkins-Katz equation

A

Takes permeability and the concentrations of each ion, average them, and then use that in the Nernst equation

182
Q

Resting potential

A

Cell’s resting potentials are typically negative, and can be explained by Na, K, and CL concentrations

183
Q

Na/K pump

A

one alpha subunit and one beta subunit

moves 3 Na ions out, and 2 K ions in

30-70% of our energy use can come from this pump

184
Q

oubain

A

binds to the 5th conformation of the Na/K pump and gets stuck there

185
Q

Calcium levels

A

High outside of the cell, low inside of the cell, high inside the ER

PMCA and SERCA are the Calcium ATPases

186
Q

The four characteristics of catilage

A

Flexible extracellular matrix

no vascularization

cells imprisoned in lacunae surrounded by an ECM of their making

Limited amount of proliferation within lacunae, resulting in interstitial growth

187
Q

How does cartilage form

A

chondroid precursor cells give rise to chondroblasts. The cartilage mass is surrounded by perichondrium (connective tissue)

188
Q

Chondroblasts

A

Secrete type II collagen and some GAG’s to produce extracellular chondroid matrix

Secrete circumferentially, as opposed to osteoblasts which secrete only in one direction

189
Q

3 types of catilge

A

hyaline, elastic, fibrocartilage

All contain type II collagen and GAG’s

190
Q

Hyaline cartilage

A

Glassy and translucent. Forms the initial models for bones and allows their growth up to puberty.

On the surfaces of bone at the synovial joints. Also in nose, trachea, bronchi.

191
Q

Elastic cartilage

A

The ear, epiglottis, has many elastic fibers

192
Q

Fibrocartilage

A

has type 1 collagen, as well as type II, giving it greater tensile strength, and is found in spinal column, knee, and ligaments. It lacks a perichondrium and contains less water in the ECM.

193
Q

What does bone store

A

Calcium and phosphate

194
Q

Bone structure

A

type 1 collagen, as well as ground substance, that is mineralized.

Spaces called lacunae that each contain an osteobyte. There cells have many processes that extend through small tunnels called canliculi

Outer surface of bone covered in periosteum containing osteoprogenitor cells. Outer layer of pereosteum is dense connective tissue, inner layer contains osteoprogenitor cells.

195
Q

Endosteum

A

Lining tissue of the compact bone and the trabeculae. Endosteal cells can differentiate into osteoblasts and bone lining cells.

196
Q

Osteoid

A

Bone extracellular matrix - secreted by osteoblasts, which are derived from osteoprogenitor cells.

197
Q

Osteoprogenitor cell differentiation

A

CBFA-1 and BMP are important factors, these progenitor cells can form many different cell types

198
Q

hydroxyapatite

A

calcium and phosphate ions in a crystalline strucutre, ordering of the collagen in the osteoid

199
Q

osteoclasts

A

break down bone matrix with the release of calcium, derived from monocytes, and are giant and multinucleated.

200
Q

Howship’s lacuna

A

space carved out of bone by an osteoclast

201
Q

Haversian system

A

An osteon, consisting of concentric lamellae of bone martix aroudn a cental haversian canal, containing the vascular and nerve supply for the osteon. The long axis of an osteon is parallel to the gdone.

Volkmann’s cannals run parallel to the haversian canal and connect them together. These are channels for blood vessels and nerves, and are not surrounded by concentric lamellae.

202
Q

Two types of bone development

A

Endochondronal (cartilage model) or Intramembranous *no carilage)

Flat bones develop by intramembranous ossification, bones of weight bearing parts come from endochondronal ossification

203
Q

Method of Endochondral bone formation

A

The periosteal collar of bones forms around the diaphysis (shaft) of the cartilage. The cartilage inside begins to calicify. Blood vessels and connective tissues cells invade the cartilage, ossification happens from the senter of the bone (diaphysis) to the ends (epiphysis).

204
Q

Periarticular chondrocytes

A

Proliferate and differentiate into columnar chondrocytes that proliferate further and form orderly columns. Regulated by parathyroid hormone

205
Q

PTHrP

A

Upregulated by Indian Hedgehog

PTHrP diffuses into the growth plate, where it keeps cells proliferating. When it stops below a certain level, cells stop proliferating.

206
Q

Cortical bone

A

Forms the outer surface of bones and does not have cavities for bone marrow or hematopoesis

207
Q

How do osteoblast signal osteoclasts

A

Osteoblasts are stimulated by Vitamin D and PTH to secrete factors that cause osteoclast precursors to proliferate. These then differentiate into mononuclear osteoclasts. Osteoclasts resorb some bone in a pit, and osteoblasts replace them to build new bone matrix.

208
Q

How are lacunae formed

A

As chondrocytes produce matrix, they become surrounded 360 degrees. They also secrete enzymes that allow them to reposition themselves.

209
Q

What type of cartilage is in the trachea? What are its components?

A

Hyaline cartilage, major components are type II collagen and aggrecan. Also contains GAGs

210
Q

What type of cartilage is the epiglottis?

A

Elastic cartilage

211
Q

What type of cartilage is stained by Resorcin-Fuchsin

A

Elastic cartilage

212
Q

RNAKL

A

expressed by osteoclast precursors, leading to increased osteoclastogenesis.

213
Q

Where are osteocytes found in the osteon

A

Found in lacunae, which conform to the shape of the cell. They extend processes through canaliculi

214
Q

How does a solute from the blood vessels reach the osteocytes

A

flows through vessels in the Volkmann’s canals to the Haversian canals and then to the osteocytes.

215
Q

How are osteoclast niches acidified

A

carbonic acid is secreted by clathrin coated lysosomes, which fuse with the ruffled membrane.

216
Q

What does increased adenyl cyclase do int he intestines in cholera

A

Makes an abnormally high amount of cAMP, which activates Cl channels, causing the cells to secrete large amounts of CL into the lumen of the intestines

Na follows this gradient of large amounts of ions

217
Q

osmotic diarrhea in lactose intolerance

A

lactose stays in the intestinal lumen, where it holds water

218
Q

What ion channel works to depolarize sterocilia hair cells

A

The K+ channel,

219
Q

Where would you find claudins in a normal epithelial cell

A

Tight Junctions

220
Q

What would a claudin defect do to hair cells

A

Impairs the ability of the epithelia to separate the endo- and peri-lymph fluids, so concentration of K+ in the endolymph would be lowered

221
Q

Non osmotic volume

A

Colume of a cell that does not pertain to shrinkage or enlargement, the rest can grow and shrink

222
Q

What will happen to osmotic volume if a cell in 150mM NaCl is placed in 300mM NaCl

A

Osmotic volume of the cell will shrink in half, however, the concentration of Cl will conversely double in the cell (effectively) so the Ecl would remain unchanged.

223
Q

What volume and resting potential would a cell acquire if placed in 150 mM NaCl and 300 mM sucrose

A

The osmotic pressure is doubled, so the new volume decreases again to 60 um. Internal Cl effectively doubles, so the Nernst equation should be recalculated . There is more Cl inside than outside, so the new Ecl is +7.5, up from -10.6

300mM sucrose has the same ionic potential as 150mM NaCl because they generate the same number of ions.

224
Q

Under what condition would a membrane potential equal a Nernst potential

A

when it is exclusively permeable to only one ion

225
Q

Name 6 components of the dermis

A

Sweat glands and their ducts, blood vessels, merkel, meissner, pacnian (all 3 corpuscles) and hair receptors.

226
Q

What cell is melanin typically found in

A

Keratinocytes

227
Q

Functions of pRB

A
  1. Represses E2F transcription factors in non dividing cells
  2. Regulated by CDK complexes
  3. CDK’s are activated by cyclins are phosphorylate pRB
  4. hyperphosphorylating pRB pushes the cell into the cell cycle
228
Q

What causes the skin’s resistance to mechanical stress

A

keratin intermediate filaments

229
Q

What are the 3 major types of ground substance

A

GAG’s, proteoglycans, and multiadhesive glycoproteins

230
Q

What is contained int he granules of each of the granulocytes

A

Neutrophils: peroxidase and lysozyme

Eosinophils: Major basic protein and peroxidase

Basophils: histamine, serotonin

231
Q

Blue spots in reticulocytes

A

polyribosomes synthesizing hemoglobin

232
Q

Several layers of cells reside within epiphyseal disks of developing long bones. Which layer anchors the disk to the bony epiphysis

A

Cells that are undergoing mitosis

233
Q

From the diaphysis to the epiphysis, layers:

A

zone of calcified cartilage, zone of hypertrophy, zone of proliferation, zone of reserve cartilage

234
Q

Donnan Equilibrium equation

A

Kout/Kin = Cl(in)/Cl(out)

Or ANY two similarly charged permeable molecules