UWorld- Endo/Biochem

Question 1

what kind of transport is responsible for glucose movement through cell membranes

Answer 1

carrier-mediated transport (the membrane proteins change conformation, but don’t use energy), which is a form of facilitated diffusion

Question 2

what enantiomer of glucose is preferred by GLUT molecules

Answer 2

D-glucose

Question 3

what is the most common cause of elevated AFP on triple test

Answer 3

dating error (underestimated gestational age, because AFP rises with gestational age)

Question 4

list the three domains of proinsulin, and describe what has to happen to generate the mature form of insulin

Answer 4

proinsulin= N-terminal B chain, C peptide connects the two flanking chains, C-terminal A chain
beta cell peptidases cleave C peptide out to form mature insulin

Question 5

what kind of drug is glyburide and what does it do

Answer 5

sulfonylureas
1st gen: tolbutamide and chlorpropamide
2nd gen: glyburide, glimepiride, glipizide

sulfonylureas increase insulin secretion (by closing beta cell K+ channel to depolarize membrane and increase Ca influx)

Question 6

what kind of drug is risperidone and what specific side effect is it known for

Answer 6

risperidone is an atypical antipsychotic (D2 receptor antagonist)
side effect= increased prolactin

Question 7

what’s the difference between the kinds of proteins that are synthesized in ribosomes attached to the RER vs. free ribosomes

Answer 7

free ribosomes synthesize cytosolic proteins/ proteins for organelles

RER ribosomes synthesize secretory, membrane-bound and lysosomal proteins

Question 8

where is the sodium-iodide symporter (NIS) found and what molecules compete with iodide to be taken up

Answer 8

NIS is found in the basolateral membrane of the thyroid follicular cell

anions like perchlorate, pertechnetate and thiocyanate compete with iodide for uptake by NIS from the blood

Question 9

would giving exogenous T3 to a patient with primary hypothyroidism cause increased or decreased levels of rT3

Answer 9

decreased rT3:
normally TSH upregulates T4, which is converted either to T3 or rT3. T3 cannot be converted to T4 or to rT3. T3 is the active form, but it also negatively feeds back on TRH and TSH levels. This would decrease T4 and thereby decrease rT3

Question 10

how does elevated estrogen cause an initial growth spurt, but short stature in adulthood

Answer 10

in childhood and during puberty estrogen increases linear bone growth, but also mediates closure of the epiphyseal plates so linear bone growth will end earlier leading to short stature in adulthood

Question 11

what are the endocrine toxicities of amiodarone and why is this the case

Answer 11

amiodarone can cause hyperthyroidism/hypothyroidism because it is 40% iodine by weight

Question 12

what amino acids are safe to be supplemented to a patient with pyruvate dehydrogenase deficiency and why

Answer 12

leucine and lysine are save to give a PDH deficiency patient because they are ketogenic and not glucogenic (meaning they produce only acetoacetate and its precursors, not pyruvate or any TCA cycle intermediates)

Question 13

why do septic shock patients usually become acidotic

Answer 13

septic shock-related hypoperfusion leads to decreased oxidative phosphorylation and in the absence of oxidative phosphorylation pyruvate gets converted to lactate (by lactate dehydrogenase)

Question 14

describe the polyol pathway that metabolizes glucose in the lens (include enzymes)

Answer 14

glucose gets taken up by cells in the lens and converted to sorbitol via aldose reductase; sorbitol is then converted to fructose via sorbitol dehydrogenase

Question 15

how does hyperglycemia cause cataracts (explain the pathophysiology using the polyol pathway)

Answer 15

under normal conditions the limited forward reactivity of the sorbitol to fructose part of the pathway allows sorbitol to be cleared from the eye
in a hyperglycemic patient build up of glucose causes build up of sorbitol that overwhelms sorbitol dehydrogenase
increased sorbitol increases osmotic pressure leading to influx of fluid into lens and consequent hydropic fibers of lens that degenerate causing opacities

Question 16

what is flutamide and how does it work

Answer 16

flutamide is a non-steroidal anti-androgen drug

it competitively inhibits androgen receptors by competing with testosterone and DHT to treat prostate cancer

Question 17

what is finasteride and how does it work

what does it treat

Answer 17

finasteride is a 5-alpha reductase inhibitor used to block conversion of testosterone to DHT
used to treat BPH and male-patterned baldness

Question 18

what does IGF-1 from the liver vs. from the hypothalamus do?

Answer 18

IGF-1 from the liver promotes bone growth

IGF-1 from the hypothalamus regulates CNS activity

Question 19

what causes decreased potassium in a DKA patient and why does this sometimes result in normal net serum potassium balance

Answer 19

diuresis due to glycosuria wastes potassium;

acidosis causes outflux of potassium in order to shift H+ into of cells

Question 20

why do you have to worry about exacerbating hypokalemia while giving insulin to treat

Answer 20

the DKA patient probably already has a decreased overall potassium content due to K+ wasting in the kidney; once the acidosis is fixed K+ will shift back into the cell and can cause hypokalemia as a result

Question 21

a patient with Lynch syndrome has a defect in what cellular process

Answer 21

nucleotide mismatch repair

Question 22

An older patient with atherosclerotic disease has cells with intracytoplasmic granules that are yellowish-brown in color. What is the molecule behind this pigment and what process causes it?

Answer 22

lipofuschin (natural result of aging and “wear and tear”) results from lipid peroxidation and free radical injury

Question 23

explain why a certain drug might reach higher serum levels when administered per rectum than when taken orally

Answer 23

a drug with high first-pass metabolism (metabolism by liver) would have low bioavailability (percent reaching the serum) because the gastric vessels drain through the portal system, but 2/3 of the rectal venous drainage goes straight to the systemic venous system via the internal iliacs

Question 24

which amino acids and which other molecules are metabolized to form propionyl-CoA

Answer 24

valine, isoleucine, methionine, and threonine as well as odd-chain fatty acids and cholesterol side chains are metabolized to form propionyl-CoA

Question 25

what do ApoE3 and ApoE4 do?

Answer 25

VLDL and chylomicron remnant uptake by hepatocytes

Question 26

what vitamin would you want to give to a patient with measles

Answer 26

vitamin A

Question 27

what enzyme converts norepinephrine to epinephrine

Answer 27

PNMT (phenylethanolamine-N-methyltransferase)

Question 28

synthesis of ALA synthase is normally inhibited by what

Answer 28

heme

Question 29

which amino acids have three titratable protons

Answer 29

histidine, arginine, lysine, glutamate, aspartate, tyrosine, cysteine

Question 30

which monosaccharide (and in what form) has the highest rate of metabolism and why

Answer 30

F-1-P;

it bypasses the rate-limiting step of phosphofructokinase-catalyzed conversion of F-6-P to F-1,6-BP

Question 31

what is the most common amino acid found in collagen

Answer 31

glycine (it is at least every third amino acid in the chain)

Question 32

what’s a common side effect of thiazolidinediones

Answer 32

fluid retention, weight gain and edema

Question 33

in addition to treating beta-adrenergic effects, how else does propranolol treat hyperthyroidism

Answer 33

propranolol decreases peripheral conversion of T4 to T3 (mechanism unknown)

Question 34

what kind of cell is most common in the pituitary vs. what kind of adenoma is most common

Answer 34

somatotrophs (GH secreting) are most common normally

prolactinomas are the most common pituitary tumor

Question 35

what electrolyte (chem 7) differences would you expect between primary and secondary adrenal insufficiency

Answer 35

in primary adrenal insufficiency all 3 zones of the cortex are out ==> hyponatremia, hyperkalemia, hypochloremia and metabolic acidosis
in secondary adrenal insufficiency mineralocorticoid production is usually spared so these patients usually don’t develop hyperkalemia or metabolic acidosis

Question 36

through what cytokine do thiazolidinediones exert their therapeutic effect and how

Answer 36

thiazolidinediones (aka glitazones) bind and upregulate PPAR-gamma (an intracellular nuclear receptor) which increases adiponectin (a cytokine) levels leading to decreased insulin resistance

Question 37

in what kind of thyroid cancer would you see Hurthle cells (large cells with eosinophilic cytoplasm)
what form of hypothyroidism also shows Hurthle cells

Answer 37

follicular thyroid carcinoma;

Hashimoto’s thyroiditis

Question 38

name two histologic features that differentiate papillary thyroid carcinoma from follicular thyroid carcinoma

Answer 38

papillary thyroid carcinoma has psammoma bodies (concentrically calcified structures) and ground glass, grooved nuclei

Question 39

describe the molecular pathway by which insulin promotes glycogen synthesis

Answer 39

insulin bind the receptor which is a tyrosine kinase –> tyrosine kinase phosphorylates insulin receptor substrate which phosphorylates protein phosphatase–> protein phosphatase dephosphorylates and thereby activates glycogen synthase
–> upregulated glycogen synthesis

Question 40

besides activating glycogen synthase, what else does protein phosphatase do (in regard to metabolic pathways)

Answer 40

protein phosphatase dephosphorylates and thereby inactivates F-1,6-BP, which is necessary for gluconeogensis
(so protein phosphatase inhibits gluconeogenesis)

Question 41

what’s an easy way to differentiate between 21-hydroxylase and 11-beta-hydroxylase deficiency

Answer 41

both 21-hydroxylase deficiency and 11-beta-hydroxylase deficiency cause female virilization, but in 21-hydroxylase there is hypotension and hyperkalemia due to absent mineralocorticoids;
where is 11-beta-hydroxylase there is hypertension (and low renin) since 11-deoxycorticosterone is increased and has mineralocorticoid activity

Question 42

what are three classic findings for glucagonoma

Answer 42

diabetes mellitus, necrolytic erythema and anemia

Question 43

jejunal ulcers should make you think of what tumor

Answer 43

gastrinoma

Question 44

what are the 3 ways that PTH increases serum calcium

Answer 44

1. increases bone resorption through osteoclast activity
2. increases gut absorption of calcium via activation of vitamin D
3. increases Ca2+ reabsorption in the DCT

Question 45

in patients with fructose intolerance what enzyme can allow for some fructose to still be metabolized for glycogen synthesis

Answer 45

hexokinase converts fructose to F-6-P, which can then be converted to glucose for glycogen synthesis or F-1,6-BP for glycolysis

Question 46

fatigue, weight loss with normal or increased food intake, polyuria, and polydipsia in a young physically active individual suggests what disease and what would you do to test for it

Answer 46

type 1 DM;

test with fasting blood glucose

Question 47

describe sensors that lead to ADH secretion

Answer 47

osmoreceptors in the hypothalamus and baroreceptors in the carotids and atria

Question 48

how can you distinguish between central DI and nephrogenic DI

Answer 48

on water restriction test administer DDAVP and observe whether the urine becomes even more concentrated;
if it does= central DI
if nothing changes=nephrogenic DI (unresponsive receptors to ADH)

Question 49

delayed puberty plus anosmia is suggestive of what disease?

what is the etiology?

Answer 49

Kallman syndrome;
caused by mutation of KAL-1 gene or FGFR-1 gene leading to failure of GnRH secreting neurons to migrate from the olfactory placode to the hypothalamus

Question 50

A female patient has amenorrhea due to prolactinoma. What complication or sequelae of a microprolactinoma (less than 10mm in size) would she have to worry about if she opted not to treat

Answer 50

osteoporosis due to downregulation of GnRH which leads to decreased FSH and LH and thereby decreased estrogen, which is important for bone density

Question 51

how does the hypothalamus regulate prolactin secretion

Answer 51

dopamine, secreted from the hypothalamus acts on D2 receptors in the lactotrophs to downregulate prolactin secretion

Question 52

what is tachyphylaxis

Answer 52

tachyphylaxis (aka rapid drug tolerance) is decreased response to a drug after repeated administration

Question 53

what is permissive effect (with regards to drug interactions)

Answer 53

when one molecule has a permissive effect on another drug it allows that other drug to reach its full potential
(e.g. NE, when administered with cortisol has a greater effect on vasoconstriction than NE administered alone; note that cortisol by itself has no vasopressive actions)

Question 54

in the TCA cycle which steps produce NADH?
which produce FADH2?
which produce GTP?

Answer 54

• NADH is generated by the 3 reactions catalyzed by isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase and malate dehydrogenase
• FADH2 is produced by rxn catalyzed by succinate dehydrogenase (succinate to fumarate)
• GTP is produced by rxn of succinyl-CoA to succinate (catalyzed by succinate thiokinase aka succinyl-CoA synthetase)

Question 55

explain how pyruvate is converted to PEP in gluconeogenesis

Answer 55

1. pyruvate is first converted to oxaloacetate by pyruvate carboxylase
2. oxaloacetate is converted to PEP by PEP carboxykinase
   (note: oxaloacetate cannot cross the mitochondrial membrane so it must either first be converted to PEP from within the mitochondria and then transported or must be transported as malate or aspartate to cytosol where cytosolic PEPCK can catalyze the rxn)

Question 56

what are neurophysins

Answer 56

carriers of ADH and oxytocin that carry them from hypothalamus to posterior pituitary

Question 57

what do acarbose and miglitol inhibit and where on the cell is it located

Answer 57

acarbose and miglitol treat T2DM by inhibiting alpha-glucosidase (a disaccharidase)

Question 58

what is the medication of choice for treatment of gestational diabetes mellitus

Answer 58

insulin

Question 59

why are non-selective beta blockers contraindicated in diabetes patients?
what kind of beta blocker could you use and why?

Answer 59

in response to hypoglycemia, the body releases Epi and NE to stimulate glucose production and decrease peripheral glucose use;
non-selective beta blockers block the adrenergic effects of Epi and NE, masking and exacerbating hypoglycemia

Question 60

what embryologic process causes lingual thyroid

Answer 60

failure of the thyroid gland to migrate properly ==> sublingual thyroid that must be surgically removed to avoid asphyxiation

Question 61

explain the metyrapone stimulation test

Answer 61

metyrapone test is used to determine if the HPA axis is functioning normally or not;
metyrapone inhibits 11-beta-hydroxylase, thereby increasing ACTH stimulation via low cortisol;
if the patient is normal, build up of 11-deoxycortisol (which doesn’t inhibit ACTH) will lead to increased 17-hyxdroxycorticosteroids in the urine, which can be measured;
if the patient has abnormal HPA axis function the metyrapone will not elicit increased urine 17-hydroxycorticosteroids

Question 62

mononuclear infiltration with germinal centers and a diffusely enlarged thyroid on physical exam is characteristic of what thyroid disease

Answer 62

Hashimoto’s thyroiditis

Question 63

what enzyme in the kidney converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol

Answer 63

1-alpha-hydroxylase

Question 64

from what cells does medullary thyroid carcinoma arise and what does it look like on histology with stain

Answer 64

medullary thyroid carcinoma arises from parafollicular calcitonin-secreting C cells;
on histology medullary thyroid carcinoma appears as polygonal or spindle shaped cells with extracellular amyloid deposits (amyloid stains with Congo red)