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Flashcards in Week 4 Problem Concepts Deck (149):
1

Intermediate filaments: fxn and classes

Fxn: resist mechanical stress (most durbale of all filaments)
Classes: nuclear lamins, keratin filaments, vimentin filaments, neurofilaments

2

Role of nuclear lamins (3)

found in nucleus of ALL cells. Play a role in gene expression, differentiation, cell cycle

3

Progeria: cause, symptoms

mutation in nuclear lamins (Lamin A). wrinkling of skin, kidney issues, MSK degeneration (Benjamin button)

4

Microtubule Fxn: 2

movement within cell, cilia/flagella

5

MT have a + end and - end. whats the difference?

(+): beta tubulin, more likely to grow

(-): alpha tubulin, more likely to shrink

6

Motor proteins associated with MT? which is used in flagella and cilia movements?

Dynein (move towards - end, towards centrosome/nucleus), seen in flagella and cilia

Kinesin (move toward + end, cell periphery)

7

what is the role of basa bodies?

serve as MT organizing center for cilia

8

dynamic instability is associated with..role

MT. they can grow or shrink at + end (GTP=grow, GDP=shrink), helps "search" for proteint to bind to

9

Taxol: effects? use?

cancer treatment; stabilizes MTs

10

B/c MT play a major role in cell division (separates chromosomes) they are often targets of....

cancer treatments

11

Colchicine: effects? use?

prevents MT polymerization; cancer treatment

12

Vinblastine: effects? use?

prevents MT polymerization

13

Actin is composed of...ATP bound?

actin monomers combined to form 2-stranded helix. free actin is ATP bound. Actin monomers in filaments are ADP bound

14

Actin filaments play a role in making what 5 structures?

Stress fibers, microvilli, contractile ring, lamellipodia, filopodia

15

Congential Myopathy: cause? symptoms?

skeletal muscle weakness caused by mutation in muscle-specific actin

16

Insulin triggers glucose uptake in what three cell types?

adipose, liver, muscle

17

describe insulin signaling

Insulin=>RTK=>IRS-1=>PI-3K=>GLUT4 containing vesicle exocytosed

18

describe the process of insulin production

1. pre-proinsulin: [signal peptide-BCA]--> produced in rER

2. proinsulin: loss of signal peptide and formation of sulfide bonds (2 between B and A, one within A) produced in rER

3. mature insulin: Cleavage of C-peptide within vesicle

19

describe the storage form of insulin. where is this seen? when is it undone?

3 AB/AB dimers of insulin surrounding a Zn ion. seen in storage vesicles. undone once contents of vesicle are released

20

compare half-life of insulin vs. C-peptide

insulin has a short half life, but C-peptide is very stable and can be used as a measure of insulin production

21

pro-enzyme convertase and insulin: role, location

used to convert pro-insulin to insulin. located within vesicle

22

what is the difference between GLUT2 and GLUT4

GLUT4 is the only insulin sensitive glucose transporter (seen in muscle cells, liver cells, adipocytes). GLUT2 is located in Beta cells (insulin producing) of pancreas and play an important role in insulin release

23

describe the signal cascade associated with insulin release from beta cell

1. Alpha and beta cells of pancreas are highly vascularized
2. increase in blood glucose increases the amount of glucose entering beta cells through GLUT2
3. increased glucose increased ATP
4. ATP inactivates K channels
5. B cell depolarizes
6. Voltage gated calcium channels open
7. Ca binds insulin vesicle and insulin released

24

describe insulin release over time?

biphasic. insulin is released in two phases: phase 1=short burst, phase 2=prolonged

(glucagon release is also biphasic)

25

In ultrasound: high f gives? low f gives?

high f=better resolution
low f= better depth/penetration

26

what are the four ultrasound probes? uses?

-phased array: adbomen, cardiac
-endoluminal: vaginal, oral, rectal
-linear: superficial
-curvilinear: abdomen

27

what is attenuation? what is the attenuation of water? air?

how much an object decreases a sound wave (higher attenuation = less signal)
water: 0
air: 12

28

what are the modes of US?

-A mode: out dated
-B mode: babies!
-M mode: beach
-Pulsed Wave Doppler
-Color doppler: red=towards, blue=going away
-Power doppler: tells if you have flow

29

what is the piezoelectric effect

this is how ultrasound works. the crystal in the US converts electrical signal to sound waves and a sound waves back to electrical signal

30

does Type I or II diabetes have a stronger familial correlation? genetic?

type II

31

What is the function of human leukocyte antigen (HLA) gene complex?

set of genes, some of which code for antigens that are presented by cells

32

which locus within the HLA complex is associated with T1DM?

DR locus

33

which alleles within the DR locus of HLA increase risk of T1DM? how?

DR3: B-cells present antigens that are targeted by antibodies

DR4: antigen present that triggers production of antibodies against insulin

34

which allele within the DR locus of HLA protects against T1DM?

DR2

35

what is MODY, cause? prevelance?

Maturity onset diabetes of the young. a type of DM (NOT T1DM or T2DM) caused by genetic defects in B cels. 1-2% of diabetes cases

36

MODY 2 cause

mutation in glucokinase of B-cells (increased B-cell glucose threshold)

37

MODY 1,3,4,5,6 cause

all caused by mutations of genes in the same pathway; delayed response to glucose uptake

38

How do you treat MODY? how does it work? is it effective?

treat with sulfonylureas. high effective monotherapy. Increase intracellular calcium and increases proinsulin secretion

39

what was the goal of the genome-wide association study?

determine if genetic differences predispose people to certain diseases

40

what did the GWA study conclude with diabetes? 2

>50 SNPs identified to increase risk for diabetes (slight increase)

new genes have been associated with diabetes

41

what are 3 weaknesses of the GWA study

association does not mean causation

not generalizable

data collected in 1980s

42

name two genes that were ORIGINALLY identified in GWA study to increase risk of diabetes

TCF7L2 gene

FTO gene

43

what is the role of TCF7L2 gene? increased risk for diabetes?

TF in Wnt signaling; proglucagon synthesis

Homozygous carriers 2x increased risk for T2DM

44

what is the role of TFO? is it an inependent risk factor for diabetes?

originally thought to be an independent risk factor for diabetes. was found to be associated with obesity (a secondary risk factor for diabetes). Fxn: methylates RNA and causes preferential production of fat (epigenetic)

45

how is lifestyle associated with epigenticc; give 2 diabetes related examples

increase carbs: influence histone modification

stress can change methylation patterns

46

diabetes is a complex disease; what does that mean

diabetes is influenced by biolgical, behavioral and environmental factors

47

what causes T1DM? how common?

immune system destroys beta cells; less than 10% of popn with diabetes

48

what causes T2DM? how common?

insulin resistance and decreased insulin production. more than 90% of popn with diabetes

49

what causes gestational diabetes? how common?

placental hormones increase amount of glucose in blood. 3-5% of pregnant women

50

what is polydipsia?

thirst

51

what is polyuria?

frequent urination

52

what Fasting blood glucose is normal? diabetic?

125 mg/dL= diabetes
70-100 =normal

53

what HbA1C value is normal? diabetic?

normal: 6.5%

54

what is the difference between IGT and IFG

IGT: impaired glucose tolerance
IFT: imparired fasting glucose

both refer to a pre-diabetic state, but represent different mechanisms of insulin resistance

55

metformin: MOA

inhibits gluconeogenesis in liver. very effective monotherapy

56

SGLT2 inhibitors: MOA

prevent glucose reabsorption in kidneys

57

TZD (MOA):

decrease insulin resistance of skeletal muscle/fat

58

what are the two types of insulin?

Note: insulin should be used always in T1DM and only in special circumstances in T2DM:

Basal insulin: long acting
bolus insulin: fast acting, after meal

59

hypoglycemia is when blood glucose is below

Below 70 mg/dL

60

what are the diabetes ABCs

A: elevated A1C
B: high BP
C: Increased LDL cholesterol

all risk factors for CVDs that are associated with diabetes

61

what are the vascular complications that arise in diabetes?

Macrovascular: heart (MI, heart failure), brain (stroke), extremities (amputations)
Microvascular: retinopathy, neuropathy, nephropathy

62

Catecholamines: what are they? where are they produced?

NE/E
produced by adrenal gland

63

what are the effects of catecholamines in skeletal muscle

increase: glycolysis, TG utilization

decrease: glycogen production

64

what are the effects of catecholamines in liver

Increase: gluconeogenesis, glycogenolysis

decrease: glycogen synthesis, glycolysis, FA synthesis

65

what are the effects of catecholamines in adipose

increase: lipolysis
decrease: TG storage

66

E/NE binds what type of receptor? activates what enzyme?

adrenergic receptor. activates cAMP-PKA

67

what explains how E can have opposing effects in liver and muscle cells?

In liver: PKA phosphorylates and inactivates PFK-2/F-2,6-BPase (no F-2,6-BP produced, glycolysis not active)

In muscle PKA phosphorylates and activates PFK-2. F-2,6-BP produced and glycolysis active.

68

glucocorticoids: role? example? produced?

long-term response to stress (gene expression). Cortisol. Adrenal gland

69

what are the effects of glucocorticoids in skeletal muscle?

increase protein degradation in peripheral muscle (increase proteasome expressions)

70

what are the effects of glucocorticoids in liver cells?

increase gluconeogenesis and glycogen production

71

what are the effects of glucocorticoids in adipose?

increase lipolysis

72

why is ethanol bad? 4

ehtanol metbaolism produces an abundance of NADH, Acetyl-Coa and ATP. This high NADH/NAD+ and high ATP causes:
-decreases glucose production (hypoglycemia)
-increased lactate production (lactic acidosis)
-Decreases FA oxiation (hyperlipidemia)
-decreases glycolysis

73

T2DM is characterized by hyperglycemia caused by...5

1. peripheral insulin resistance
2. progressive B-cell dysfunction
3. hype-secretion of glucagon
4. accelerated gastric emptying
5. impaired incretin effect

74

Incretin: produced, role,

hormone produced by cells of the gut. increase insulin production following a meal.

75

incretin effect

more insulin is produced following a meal than following an IV injeciton with the same amount of glucose

76

what are the insulin and glucagon levels after a meal in a person with T2DM?

insulin: delayed and depressed levels

glucagon: non-suppressed

77

GLP-1 produced, fxn 7

incretin produced by L-cells of distal ileum and colon.
Fxn: increase insulin, increase size of Beta cells, suppress glucagon, enhance insulin sensitivity, slows gastric emptying, cardioprotection and neuroprotection

78

GIP produced? fxN 2

produced by gut K-cells of duodenum and jejunum

fxn: increase insulin release, increase size of B-cells

79

is GLP-1, GIP, or both a therapeutic target for T2DM?

only GLP-1, GIP levels are not typically altered in T2DM

80

incretins are degraded by?

DPP-4

81

Exenatide (Byetta) fxn, how do you admin?

GLP-1 receptor agonist, 2x daily injections

82

Liraglutide fxn, how do you admin?

modified synthetic GLP-1, 1x daily injected

83

Vildagliptin/sitagliptin fxn, how do you admin

DPP4 inhibitors (1x daily ingestion)

84

when blood glucose decreases, what is the normal progression of events in CRH?

glucagon-->E/NE-->Cortisol/Growth hormone

85

what are the four CRH? overall role?

Glucagon, Catecholamines, Glucocorticoids, Growth Hormones. Increase blood glucose levels

86

in T1DM>5 years what is lost completely?

Glucagon response

87

what is hypoglycemia induced autonomic failure

E/NE response decreased after recurring hypoglycemia; after glucagon response is lost E/NE becomes new line of defense

88

what causes Diabetic Ketoacidosis

Hyperglycemia and ketonemia (increased ketones in blood). Body cant use glucose even though it is present. FA oxidation occurs and ketone bodies accumulate. Excess ketones and glucose causes increase in urine volume. Further concentration of ketones in body,

89

what are the physical findings of DKA

tachycardia, dehydration, respiratory distress, coma, abdominal tenderness

90

DKA is a characteristic of what type of DM?

T1DM; although it can be triggered in T2DM

91

what is acanthosis nigricans? what is it an indication of? cause

darkening of skin fold as a result of INSULIN RESISTANCE (insulin binds IGF receptor and stimulates keratinocyte growth). High risk for developing T2DM

92

rank the order of these:
insulin resistance
impaired glucose tolerance
T2DM
increased plasma glucose

Normal--> increased plasma glucose-->insulin resistance-->impaired glucose tolerance-->T2DM

93

A patient was just diagnosed with polycystic ovary syndrome; what are they at an increased risk of?

increased risk of insulin resistance and therefore T2DM

94

how is cushing's syndrome associated with an increased risk for diabetes

excess cortisol; glucose levels raised too high-->insulin resistance-->T2DM

95

how is acromegaly associated with an increased risk for diabetes?

excess GH; blood glucose chronically elevated

96

Diabetes Prevention Program: setup, findings

3 pre-diabetes groups; placebo, metformin, lifestyle change

Lifestyle change>metformin>placebo in preventing T2DM

(1kg weight loss correlated with 16% reduction in incidence of T2DM)

97

The DPP found that metformin was only useful in individuals with...

BMI>35

98

Look AHEAD study: setup, findings

will intensive lifestyle intervention (lose 7-10% of weight by diet, exercise, pillls) reduce the incidence of cerebrovascular/cardiovascular event.

ILI group had better ABCs

99

FInnish Diabetes Prevention study findings

individualized advice is more effective than generalized diet instructions for preventing T2DM

100

what is the legacy effect?

early glucose control (diet, exercise, lifestyle changes) will have a lasting postive impact

101

what are the physical activity recommendations for adults?

30 min PA/day ~5 days/wk

102

role of nodal cilia

motile cilia that plays role in L+R asymmetry during embryo development

103

Primary Ciliary Dyskensia: cause, results in (3)

auto rece disorder caused by Loss of dynein (essential in motile cilia). Loss of mucociliary escalator, immotile sperm, and situs inversus (NOT caused by loss of primary cilia)

104

Autosomal Dominant Polycystic kidney Disease (ADPKD); cause, results in

loss of polycystin proteins essential for primary cilia (non-motile;used for mechanoreceptors)

large cystic kidneys

105

Cell Adhesion Molecules invovled in cell-cell connecitons

Cadherin and Integrin

106

Cadherin; role, intracellular domain, extracellular domain

cell-cell interaction; intracellular=associate with cetenins; extracellular domain=calcium dependent

107

General structure/fxn of cell-cell CAMs

transmembrane proteins that link interior of cell to ECM or other cells

108

intergrins; role,

cell-cell and cell-ECM binding, mechanoreceptors

109

cell jxns of lateral domain (in order from apical to basal)

Zonula Occludens (tight jxn), Zonula Adherin (intermediate jxn), Macula Adherin (Desmosome), Gap Jxn

110

Role of Zonula Occludens; important proteins

separate apical and basal domains.

Occludin, claudin

111

Role of Zonula Adherens; important proteins

anchor adjacent cells; cadherins, catenins, actin

112

role of Macula Adherens; important proteins

resist shearing force (spot welds);

desmoglein, desmocolin (Cadherin), desmoplakin, plakoglobin, keratin

113

Role of gap jxn; important protieins

cell-cell communication

connexin and connexons

114

types of basal domain jxns

focal adhesions, hemidesmisomes

115

focal adhesion; role, proteins

link cytoplasmic actin and the ECM, relay signals from ECM to cell

integrins, fibronectin, collagen, laminin

116

hemidesmisomes; role, proteins

anchors basal PM to basal lamina

BP230, Type XVII collagen, Type VII collagen, integrins

117

Pemphigus Vulgaris: cause, blister type, nikolsky sign

-skin disorder; body creates antibody against desmogleins (desmosome); loss of lateral domain but basal domain still attached to BM

-flaccid (easily popped) blisters

-Nikolsky sign +

118

Bullous Pemphigoid: cause, blister type, nikolsky sign

-skin disorder; body creates antibodies against BP230 or collagen XVII (hemidesmosomes); basal domain lost (epidermis and dermis separated)

-tense blister (not easily popped)

-nikolsky -

119

Dystrophic Epidermolysis Bullosa: cause, symptoms

-Group of inherited diseases resulting from mutated basal domain (inherited defect in collagen VII); epidermis and dermis separated,

-Skin literally falls off, esophageal symptoms as well

120

what is alpha-phase of drug distribution, beta-phase?

alpha: sharp decline in plasma drug concentration due to plasma protein/tissues binding drug

beta phase: gradual loss of drug from metabolism and excretion

121

phase of drug metabolism

phase I: Cytochrome P450 (ER membrane of liver cells); oxidation, hydrolysis, reducction

phase II: addition of larger group that make the drug more polar and easily excreted

122

Vd eqn

Vd=amount of drug given/[plasma drug]

123

what eqn relates t(1/2), Vd, and CL

t(1/2)=(.693(Vd))/CL

124

what eqn relates k, CL and Vd

k=CL/Vd

125

what four processes (performed on a drug) occurs when we take in a drug?

ADME
Absorption, Distribution, Metabolism, Excretion

126

what is Css in regard to drug accumulation

the steady state concentration of a drug accomplished when rate of intake=rate of elimination

127

for an IV: relate Css and rate of admin, Clearance

Css directly proportional to rate of admin, inversely proportional to CL

128

what factors will alter the time to reach a Css

factors that alter t(1/2) such as altering clearance or metabolism of a drug. rate of infusion will NOT change the TIME to reach Css

129

for oral admin drugs relate Css and frequency of dose, dose interval, dose of drug, CL, fraction of drug absorbed

directly proportional: frequency of drug, dose of drug, fraction of drug absorbed

Inversely proportional: CL, dose interval

130

what are the three functions of sER

lipid synthesis (steroid hormones in adrenal cortex), calcium storage (muscle cells), detoxification (Cyt P450 in sER membrane of liver cells)

131

the sER of liver aids in detox of what two substances (high yield)

ethanol, barbiturates

132

Role of CYP2C9 detoxes what? 3

hydroxylates drugs such as warfarin, phenytoin (anticonvulsant), tolbutamide (insulin release stimulator)

133

Warfarin; complication, genes involved, is screening required

3% of people have bleeding during first month. VKORC1 gene (drug target of warfarin) and CYP2C9 gene (Cyto P450 that metabolizes warfarin). FDA does not require screening

134

CYP2D6 metabolizes what 4

Anti-psychotic, antidepressants, metoprolol (decrease BP), tamoxifen (anti-cancer pro-drug)

135

CYP2D6 inhibited by (4)

coke, prozac, paxil, protease inhibitors

136

metabolizer groups of CYP2D6

poor metabolizer (LOF), intermediate metabolizer, efficient metabolizer, utrarapid metabolizer (*2xn=increase copy number)

137

what is the active from of the pro-drug tamoxifen

endoxifen

138

three people; one is UM, one is PM, one is IM. each take same dose of tamoxifen, who has the most benefit

UM because there is more active from of the drug

139

for non pro-drugs how should you augment dose for individuals who are UM, PM

UM: increase dose
PM: decrease dose

140

does FDA require genetic screening prior to Tamoxifen use?

no

141

G6PD def has a higher risk for ADRs when taking? genetic screen?

rasburicase, uricemia, primaquin, dapsone

genetic screen is recommended

142

HLA-B*1502 has a higher risk for ADRs (steven-johnson syndrome) when taking? genetic screen?

carbamazepine; screen recommended

143

HLA-B*5701 has increase risk for ADRs when taking? genetic scree?

abacavir. screen recommended

144

TPMT-deficient have increased risk of ADRs when taking? screen?

azathiorprine

screen recommended

145

role of TPMT

phase II inactivation of thiopurines (immuno-suppresant). if thiopurines accumulate leukopenia occurs (drop in plasma WBCs)

146

Imatinib has increased efficacy in... screen?

C-KIT-positive GI tumors. Screen required

147

Maravicor has increased efficacy in....screen?

treating CCR5-tropic HIV-1
screeen required

148

Trastuzumab has increased efficacy in....screen?

treating HER-2 positive breast cancer. screen required

149

Pre-diabetes values for A1C and Fasting Blood Glucose

A1C: 5.7-6.5%
FBG: 100-125 mg/dL

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