8/28/17

Question 1

Insulin, GLUT-4, and Glucose Uptake

Answer 1

Insulin binds to its receptor and causes signaling via IRS-1 and PI3K

GLUT4 fuses with PM and does facilitated transport

GLUT4 found in skeletal/cardiac muscle and adipose tissue, brain has glucose transporter that doesn’t rely on insulin

Question 2

Post-translational modifications of insulin

Answer 2

1. Start as preproinsulin, put in lumen of rough ER by signal peptide
2. Signal peptidase removes the signal peptide as enter rough ER, makes proinsulin (inactive)
3. Folding of the disulfide bond formation (between A and B chain) occurs in the rER, sent to Golgi and then sent to secretory vesicles
4. Cleavage of C chain occurs in secretory vesicles by prohormone convertase, C peptide and insulin secreted together

Question 3

Insulin Structure

Answer 3

1°: A chain shorter than B chain and also has an intrachain disulfide bond, has two interchain disulfide bonds

2°: Chain A has 2 alpha helices connected by disulfide bond, Chain B is an alpha helix

3°: A and B chains are perpendicular to each other

4°: six insulin molecules arranged around Zn ions surrounded by His

Storage form for secretory vesicles that dissociates into monomeric active forms after secretion

Question 4

Insulin Secretion

Answer 4

Glucose enter beta cells via GLUT2

Glycolysis and ATP generation increase

ATP inhibits plasma membrane K+ channels, altered membrane potential opens voltage-gated Ca2+ channels

Incoming Ca2+ triggers export of storage granules by exocytosis

Biphasic Insulin Release
Rapid/transient insulin secretion at first by vesicles close to the PM and then a delayed but more sustained release of insulin

Second phase of release requires monomeric GTPases and vesicles movement by rearrangement of actin cytoskeleton

Question 5

Glucagon structure

Answer 5

Simple alpha helix

Made as a preprohormone that has the signal peptide cleaved in the rER

Prohormone contains peptides for several hormones like GLP-1, cut by tissue-specific prohormone convertases

Question 6

Glucagon Secretion

Answer 6

Not entirely clear

Low Glu triggers voltage-gated Ca2+ channels to let Ca2+ in the cell, expcytosis of glucagon vesicles

Biphasic release since two pools of glucagon

Question 7

Effects of malnutrition during pregnancy

Answer 7

Glucose-insulin disorders
Cardiovascular disease
Renal dysfunction 
Airway disease
Breast cancer 
Obesity

Question 8

Kidney Hypertension from uterus

Answer 8

Insult to fetus like malnutrition, lack of protein, or glucocorticoid exposure slows tissue growth and leads to lower cell number

Nephrons have a higher glomerular filtration rate per cell to compensate and focal glomerulosclerosis occurs (leads to scarring and death)

Sodium builds up in blood and get high blood pressure

Adaptations as a fetus become maladaptive as an adult

Question 9

Mid Brain

Answer 9

Develops first and fast

Emotional outbursts: fear, anxiety, impulsive, stressed, reactive

When get emotional they use all 5 senses and remember the experiences with long term memory

Question 10

Front Brain

Answer 10

Develops slowly

Calculating

Plans ahead, thinks fast, multitasks, logical, organized

Question 11

Prefrontal Cortex

Answer 11

Emotions: managing frustrations, modulating emotions

Activation, focus, effort, memory, action

Not fully developed until young adulthood

Question 12

HPA Axis

Answer 12

Plays a role in response to stress

Stress: any real or perceived threat to homeostasis

Hypothalamus releases Corticotropin-releasing factor (CRF) to anterior pituitary, which releases adrenocorticotropic hormone to the adrenal cortex

Adrenal cortex releases cortisol, a glucocorticoid

Question 13

How children can avoid toxic stress from Adverse Childhood Events

Answer 13

Social and Emotional Buffers

Question 14

3 Executive Functions for Learning Something

Answer 14

Self-Control: ignore distractions, control emotions, stay focused

Working Memory: remember and connect, manipulate info, perform multiple steps

Flexible Thinking: switch perspectives, assess different strategies

Question 15

Scaffolding

Answer 15

Adult support throughout everyday routines: highly responsive, encouraging, interactive, and playful

Question 16

Intermediate Filament

Answer 16

Rope-like structures that can withstand mechanical stress

Toughest and most durable

Act as desmosomes and form nuclear lamina

Alpha helices that bundle in opposite directions, have no structural polarity

Question 17

Classes of intermediate Filaments

Answer 17

1. Keratin filaments: each type of epithelial cell has its own type of keratin filament
2. Vimentin and vimentin-related filaments: connective tissue, muscle cells, and glial cells
3. Neurofilaments: in nerve cells
4. Nuclear lamins: in all animal cells, provide support and also involved in nuclear organization, cell cycle regulation, and gene expression

Question 18

Defective Intermediate Filaments

Answer 18

1. Epidermolysis Bullosa Simokex: skin blistering after little mechanical stress, mutation in the skin-specific keratin gene
2. Progeria: the nuclear lamina on he inside of the nuclear membrane is defective

Can’t provide support so get misshapen nucleus that affects chromatin organization, cell division, and gene expression

Age prematurely so have hair loss, wrinkles, CV/kidney problems, die in teens

Question 19

Microtubules

Answer 19

Hollow, rigid rods that are like RR tracks for vesicles, organelles, and other things

Made of alpha and beta tubulin stacked on top of each other, 13 parallel chains called protofilaments

Beta end is plus end, polymerize faster
Alpha end is minus end, polymerize slower

Grow out of centrosome that has 2 perpendicular centrioles, gamma tubule is a matrix protein that acts as a nucleation site

Found in cilia (lung epithelium) and the centrioles are called basal bodies, also do mitotic spindle

Question 20

Microtubule Dynamic Instability

Answer 20

Like fisherman, will stop growing if not bind to specific proteins or cellular components

Alpha/beta tubule dimers added to plus end if have GTP bound

GTP becomes hydrolyzed to GDP, GDP-tubulin not bind to stuff as well so will depolymerize

GTP cap if add GTP tubulin faster than hydrolyze to GDP

Question 21

Microtubule drugs

Answer 21

Prevent polymerization or stabilize so can’t shrink, used for tumor cells with rapid cell division

Taxol: stabilize microtubules

Colchicine, Vinblastine: prevent polymerization

Question 22

Microtubule transport

Answer 22

Used in nerve cells with long axons, motor proteins direct cargo movement

Kinesins: walk toward plus end (cell periphery)
Dyneins: walk toward minus end (centrosome)
Different kind of each, tail binds specific cargo

Question 23

Cilia and Flagella

Answer 23

Cilia in respiratory tract to move mucus, sperm have flagella

9 + 2 array with 9 doublets outside and 2 singles inside, use dyneins

Cilia in inner ear (used for sensory input) and in respiratory tract

Are stable, no dynamic instability

Question 24

Actin Filaments

Answer 24

Create cell shape and movement, regulated by many different types of proteins

Polymerization of actin monomers into two stranded helix

Has cleft for ATP, can be hydrolyzed to ADP to create depolymerization

Faster growing plus end and slower minus end but can grow/shrink at both ends, do treadmilling, less rapid rate of change compared to microtubules

Stress bundles, contractile ring for dividing cells, transient cellular projections, microvilli

Question 25

Microvilli

Answer 25

Made of actin filaments Small intestines and kidney tubules Non-motile, increase surface area of the cell membrane to improve absorption

Question 26

Cell Migration via Actin

Answer 26

Lamellipodia: broad thin sheets that have dense actin network Filopdia: long stiff finger-like projections with parallel actin filaments Plus ends oriented towards PM that pushes the membrane outward

Question 27

Myosin II

Answer 27

Muscle Cell: 2 myosin II can associate tail to tail to form myosin thick filament, create muscle contraction Non-muscle Cell: double myosin II facing opposite direction walks the head along actin filament towards plus end to create cell contraction Creates stress fibers- regulate cell shape, cell division, migration, and sensing of mechanical stress Regulated by Rho GTPases (monomeric G protein from Ras family) that create downstream signaling to do stuff like filopedia

Question 28

Congenital Myopathy

Answer 28

Skeletal muscle weakness that can be neonatal life threatening to mild muscle weakness in adults No cure Mutations in the actin cytoskeleton, can be a number of ways

Question 29

Ultrasound propagation

Answer 29

Use pulse echo technique, utilizes a crystal Duty factor: how much the ultrasound is actually on Pulsed wave: 1% or 0.01 Continuous wave: 100% or 1.0

Question 30

Velocity and Attenuation of Ultrasound by different media

Answer 30

Velocity: air slowest at 330, tissues are middle and 1500, bone fastest at 4080 Attenuation: water lowest at 0, tissues middle at 1, bone at 5, air highest at 12

Question 31

Scanning planes and field edges for ultrasound

Answer 31

Sagittal: divides body into left and right Coronal: divides body into front and back Transverse: divides body into top and bottom Near field: closest to probe Far field: furthest from probe Leading edge: closest to indicator mark Receding edge: furthest side from indicator

Question 32

Grayscale colors for ultrasound

Answer 32

Black (Anechoic): fluid like blood or bile Gray (Hypoechoic): soft tissue and solid organs, includes muscle White (Hyperechoic): air, bone, dense fascia, includes diaphragm

Question 33

Ultrasound Modes

Answer 33

A Mode: amplitude, used rarely and in ophtho B Mode: brightness, common M Mode: motion, displays anatomy over time

Question 34

Medical vs Surgical Asepsis

Answer 34

Asepsis: the state of being free from pathogenic microorganisms Medical asepsis: clean technique to reduce /prevent spread of pathogens like hand washing, glove use, and cough etiquette Surgical asepsis: sterile technique, practices to eliminate all microorganisms from an area, used for invasive procedures

Question 35

Principles of Sterile Technique

Answer 35

``` Never turn back on sterile field Don't reach over sterile field Can become non-sterile if prolonged exposure to air Moisture contaminates sterile field Skin not sterile Check package sterility Consider not sterile when in doubt Items in sterile field must be sterile One inch border around sterile field is nonsterile Anything below waist is not sterile ```

Question 36

SGLT2 Inhibitors

Answer 36

Sodium Glucose Co-Transporter 2 SGLT2 normally reabsorbs 90% of the glucose that is filtered by the kidney, located in the proximal convoluted tubule SGLT2 Inhibitors prevent reabsorption, glycosuria, lose weight

Question 37

Hypoglycemia

Answer 37

Glucose less than 70 Rule of 15: have 15g of carbs and check back in 15 mins, repeat if necessary Causes: missed meal, too much exercise or insulin Severe hypoglycemia associated with higher CV mortality and cognitive dysfunction

Question 38

Macrovascular Diabetes Complications

Answer 38

Most common cause of diabetes death Include coronary artery disease, cerebrovascular disease, and complications of peripheral vascular disease Heart: myocardial infarction (heart attack), heart failure (heart pump failure) Brain: stroke, cognitive impairment Extremities: ulcers, amputations, aneurysms

Question 39

Microvascular Complications of Diabetes

Answer 39

Eye: retinopathy, cataracts, glaucoma that can lead to blindness Kidney: neuropathy like macro/microalbuminuria that can lead to kidney failure Nerves: peripheral/autonomic neuropathy that can lead to amputation All can lead to disability or death

Question 40

3 key junctions in metabolism

Answer 40

Glucose-6 phosphate: can lead to glycogen, pyruvate, or ribose 5-phosphate Pyruvate: can lead to oxaloacetate, alanine, or lactate Acetyl CoA: FAs, CO2, and ketone bodies

Question 41

Common Characteristics in Metabolic Regulation

Answer 41

Allosteric Interactions: PFK1 is stimulated by fructose 2,6 bisphosphate Covalent Modification: phosphorylation of glycogen synthase inhibits the formation of glycogen Adjustment of Enzyme Levels: glucagon induces expression of PEP carboxykinase, glucagon triggers gluconeogenesis of oxaloacetate into PEP Compartmentation: transport of FAs into mitochondria for degradation Metabolic specialization of organs

Question 42

Glycogen Break Down

Answer 42

1. Glucagon (in the liver only) or epinephrine (via a beta receptor) binds to a G protein receptor, activates adenylate cyclase to make cAMP 2. cAMP activates PKA 3. PKA activates phosphorylase kinase 4. Phosphorylase kinase converts inactive glycogen phosphorylase b to active glycogen phosphorylase a 5. PKA inactivates glycogen synthase by phosphorylation 6. Glycogen is degraded to Glu 1-phosphate

Question 43

Effect of catecholamines on different body areas | Epinephrine

Answer 43

Released by kidneys upon sympathetic NS signals, get acute response 1. Muscle- Greatly increased: glycolysis, glycogenolysis Slight Increase: gluconeogenesis Moderate decrease: glycogen synthesis Liver- Greatly increased: glycogenolysis Slight increase: gluconeogenesis Slight decrease: glycolysis, FA synthesis Adipose tissue- Greatly increased: Lipolysis Slight decrease: triglyceride utilization

Question 44

Fructose 2,6-bisphosphate

Answer 44

Fructose 2,6-bisphosphate activates PFK1 in liver and muscle to promote glycolysis PFK2 makes it, different isoform for muscle and liver Epinephrine causes PKA-cAMP to phosphorylate each isoform Phosphorylation stimulates Fructose 2,6-bisphosphate in the muscle to turn on glycolysis, inactivates liver isoform to stop making Fructose 2,6-bisphosphate

Question 45

Effect of glucocorticoids on different body areas | Cortisol

Answer 45

Chronic stress causes corticotropin-releasing factor in the hypothalamus to be released, leads to glucocorticoids in the adrenal cortex to be released Regulates gene expression, takes hours or days 1. Muscle: Protein degradation in peripheral tissues slightly increased 2. Liver: gluconeogenesis and glycogen synthesis slightly increased 3. Adipose tissue: lipolysis and expression of lipase slightly increased

Question 46

Ethanol Metabolism

Answer 46

Alcohol Dehydrogenase System- occurs in cytoplasm of the liver Ethanol to acetaldehyde to acetate, use NAD+ Microsomal Ethanol-Oxidizing System: used for large amounts of alcohol Use O2 and NADPH to convert ethanol to acetaldehyde, which feeds back to cytoplasm for further detox

Question 47

Effect of Alcohol on Liver Metabolism

Answer 47

Alcohol metabolism makes large quantities of acetyl-CoA, NADH, and ATP TCA cycle inhibited by high ATP and NADH levels, glycolysis inhibited at PFK1 and PDH FA oxidation impaired by NAD+ depletion Gluconeogenesis inhibited cuz high NADH:NAD+ ratio drives lactate dehydrogenase towards lactate and malate dehydrogenase towards malate instead of pyruvate and oxaloacetate Alcohol precipitates hypoglycemia

Question 48

Health Requirements for Adults

Answer 48

25-45 kcal/kg for adult male, 25-35 for girls Fewer kcal needed as we age, young people have the highest Avoid chronic diseases, do prudent diet

Question 49

Nutrition Requirements for Infants

Answer 49

Feed every 2-3 hours, double birth weight by 4 months, height by one year Breast milk is better than bottle, low in protein and high in fats (good for babies though), higher conc. of immune components and growth factors, reduce illness 108 kcal/kg for first 6 months, want 7% calories from protein (half of adult amount), higher fats and avoid ketosis, less carbs than adult Supplement with iron for first year and folate/B12 for first 6 months Wean at one year

Question 50

Nutrition for Lactating Moms

Answer 50

Normal healthy diet Takes about 750 kcal to make milk each day Take in polyunsaturated fats Slight increase in protein

Question 51

Nutrition for Toddlers

Answer 51

Picky eaters, developing healthy habits is crucial for later in life, less appetite since less growth so make eat 70-90 kcal/kg, want ideal growth specified by WHO not CDC, after 2 keep fat intake like adults, less protein and more carbs than adults, fluids since dehydrate faster than adults Iron (anemia a big problem), zinc, and calcium are important

Question 52

Iron deficiency and anemia symptoms (stages II and III)

Answer 52

Impaired body temp regulation so always cold, decreased immune function, sensitivity to light, pica, koilonychia (spoon nails), angular stomatitis (lesions around mouth), up susceptibility to lead poisoning

Question 53

Nutrition for Childhood

Answer 53

Need nutrient dense foods, but needs vary greatly Energy to ensure growth and spare protein degradation but not allow excess weight gain Energy intake similar to an adult Monitor calcium, iron, zinc, and vitamin D

Question 54

Nutrition for Adolescence

Answer 54

47-65 kcal/kg with males needing more Calcium important for acquiring bone mass, Vitamin D is crucial Iron important for deposition of lean muscle mass and iron lost during menses Folic Acid important for lean body mass and females of reproductive age

Question 55

Nutrition for Old People

Answer 55

Lose lean mass, more sedentary BMR declines so need slightly less calories Vitamin C, B6, and B12 deficiency are common Nutrients for repair/maintenance: A, D, Fe, Ca, and protein Fiber and poly fats help fight disease Exercise helps with cancer and CV probsq

Question 56

Effects of Insulin

Answer 56

Anabolic hormone Protein synthesis, glycogen synthesis, lipogenesis Inhibits the catabolism of each of these

Question 57

Role of FFA in Hyperglycemia

Answer 57

Adipose tissue insulin resistance leads to increased lipolysis and FFA mobilization as a result FFA mobilization creates muscle insulin resistance by increasing FFA oxidation, causing lower glucose utilization FFA mobilization creates liver insulin resistance by increasing FFA oxidation, increasing gluconeogenesis Creates hyperglycemia

Question 58

Mechanism of insulin resistance

Answer 58

Primary mechanism not known but probably a combo of genetics, obesity, cytokines, and FFAs Insulin receptor levels and tyrosine kinase activity in skeletal muscle are reduced, most likely to hyperinsulinemia and not primary defect Post receptor defects in insulin regulated phosphorylation and dephosphorylation play a predominant role

Question 59

Insulin receptor and insulin signal transduction

Answer 59

Insulin binds to receptor tyrosine kinase Interacts with IRS and Shc proteins for cell growth, protein synthesis, glycogen synthesis, and glucose transport PI-3 kinase and the Cbl pathway promote translocation of intracellular vesicles with GLUT4 transporters to the PM

Question 60

Clinical Features of Insulin Resistance

Answer 60

Central/android obesity Acanthosis nigricans: hyperpigmentation and velvety plaques, high insulin levels bind to IGF receptors to stimulate growth of keratinocytes/dermal fibroblasts, can be painful and smelly, goes away with weight loss Metabolic syndrome Associated with Hypertension and dyslipidemia

Question 61

Progression of Insulin Levels and beta cell mass before Diabetes

Answer 61

Insulin Secretion initially increases to maintain normal glucose levels, mild secretory defect initially Eventually insulin secretory defect progresses to inadequate insulin secretion Beta cell mass decreases by 50% when diagnosed, amyloid deposit in islet cells, elevation of FFAs (lipotoxicity) may worsen islet function

Question 62

Incretin

Answer 62

Gut hormones released from intestine in response to ingestion of food like glucose, need sufficiently high conc. to stimulate release of insulin, release of insulin in response to physiological levels of the hormone occurs only when glucose levels are elevated (Glu-dependent) Glucagon-like Peptide 1 (GLP-1) and Gastric Inhibitory Peptide (GIP), both rapidly metabolized by dipeptidyl peptidase-4 (DPP-4) Both stimulate insulin response from beta cells in glucose-dependent manner GLP-1 inhibits gastric emptying, reduces food intake, and inhibits glucagon Secretion from alpha cells in glucose-dependent manner unlike GIP Reduced incretin effect in diabetics

Question 63

Drug Induced Diabetes

Answer 63

Glucocorticoids Steroids Immunosuppressants Niacin HAART Atypical antipsychotics Diazoxide

Question 64

Polycystic Ovary Syndrome

Answer 64

Insulin resistance Obesity Irregular menses Reduced fertility Hyperandrogenism (guy hair patterns)

Question 65

Gestational Diabetes

Answer 65

Due to placental hormones (human placenta lactogen) which promotes insulin resistance through various mechanisms to increase nutrient supply to growing fetus Higher risk for subsequent diabetes

Question 66

Stress Hyperglycemia

Answer 66

Critically ill, ICU, burn victims May or may not be reversible Increased cortisol, catecholamines, glucagon, growth hormones, gluconeogenesis, and glycogenolysis Underlying insulin resistance a contributing factor

Question 67

Cushing's Syndrome and Acromegaly

Answer 67

Cushing's: excess cortisol Associated with Central obesity, diabetes, Hypertension, muscle wasting Acromegaly: excess growth hormone Associated with Diabetes, Hypertension, sleep apnea

Question 68

Type II Treatment

Answer 68

Entry A1C <7.5%: monotherapy, metformin Entry A1C >7.5%: dual therapy, metformin plus another drug Entry A1C >9%: dual or triple therapy if no symptoms, insulin and other agents if symptoms

Question 69

DPP-4 Inhibitors (Gliptin Family)

Answer 69

Inhibit the enzyme DPP-4 that breaks down GLP-1 and GIP Both incretins have an insulintropic effect leading to clearance of glucose from bloodstream Incretins stay in system from 12 hours to several days Lower A1C levels and do weight loss

Question 70

How to Assess a Type II patient

Answer 70

Start with basics and don't overwhelm Assess their resources and support system Make initial weight loss goal of 5-10% Give education: starting new meds, nutrition counseling like what a carb is Short term follow up with reachable short term goals