UWorld- Endo/Biochem Flashcards
what kind of transport is responsible for glucose movement through cell membranes
carrier-mediated transport (the membrane proteins change conformation, but don’t use energy), which is a form of facilitated diffusion
what enantiomer of glucose is preferred by GLUT molecules
D-glucose
what is the most common cause of elevated AFP on triple test
dating error (underestimated gestational age, because AFP rises with gestational age)
list the three domains of proinsulin, and describe what has to happen to generate the mature form of insulin
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
what kind of drug is glyburide and what does it do
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)
what kind of drug is risperidone and what specific side effect is it known for
risperidone is an atypical antipsychotic (D2 receptor antagonist)
side effect= increased prolactin
what’s the difference between the kinds of proteins that are synthesized in ribosomes attached to the RER vs. free ribosomes
free ribosomes synthesize cytosolic proteins/ proteins for organelles
RER ribosomes synthesize secretory, membrane-bound and lysosomal proteins
where is the sodium-iodide symporter (NIS) found and what molecules compete with iodide to be taken up
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
would giving exogenous T3 to a patient with primary hypothyroidism cause increased or decreased levels of rT3
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
how does elevated estrogen cause an initial growth spurt, but short stature in adulthood
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
what are the endocrine toxicities of amiodarone and why is this the case
amiodarone can cause hyperthyroidism/hypothyroidism because it is 40% iodine by weight
what amino acids are safe to be supplemented to a patient with pyruvate dehydrogenase deficiency and why
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)
why do septic shock patients usually become acidotic
septic shock-related hypoperfusion leads to decreased oxidative phosphorylation and in the absence of oxidative phosphorylation pyruvate gets converted to lactate (by lactate dehydrogenase)
describe the polyol pathway that metabolizes glucose in the lens (include enzymes)
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
how does hyperglycemia cause cataracts (explain the pathophysiology using the polyol pathway)
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
what is flutamide and how does it work
flutamide is a non-steroidal anti-androgen drug
it competitively inhibits androgen receptors by competing with testosterone and DHT to treat prostate cancer
what is finasteride and how does it work
what does it treat
finasteride is a 5-alpha reductase inhibitor used to block conversion of testosterone to DHT
used to treat BPH and male-patterned baldness
what does IGF-1 from the liver vs. from the hypothalamus do?
IGF-1 from the liver promotes bone growth
IGF-1 from the hypothalamus regulates CNS activity
what causes decreased potassium in a DKA patient and why does this sometimes result in normal net serum potassium balance
diuresis due to glycosuria wastes potassium;
acidosis causes outflux of potassium in order to shift H+ into of cells
why do you have to worry about exacerbating hypokalemia while giving insulin to treat
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
a patient with Lynch syndrome has a defect in what cellular process
nucleotide mismatch repair
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?
lipofuschin (natural result of aging and “wear and tear”) results from lipid peroxidation and free radical injury
explain why a certain drug might reach higher serum levels when administered per rectum than when taken orally
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
which amino acids and which other molecules are metabolized to form propionyl-CoA
valine, isoleucine, methionine, and threonine as well as odd-chain fatty acids and cholesterol side chains are metabolized to form propionyl-CoA
what do ApoE3 and ApoE4 do?
VLDL and chylomicron remnant uptake by hepatocytes
what vitamin would you want to give to a patient with measles
vitamin A
what enzyme converts norepinephrine to epinephrine
PNMT (phenylethanolamine-N-methyltransferase)
synthesis of ALA synthase is normally inhibited by what
heme
which amino acids have three titratable protons
histidine, arginine, lysine, glutamate, aspartate, tyrosine, cysteine
which monosaccharide (and in what form) has the highest rate of metabolism and why
F-1-P;
it bypasses the rate-limiting step of phosphofructokinase-catalyzed conversion of F-6-P to F-1,6-BP
what is the most common amino acid found in collagen
glycine (it is at least every third amino acid in the chain)
what’s a common side effect of thiazolidinediones
fluid retention, weight gain and edema
in addition to treating beta-adrenergic effects, how else does propranolol treat hyperthyroidism
propranolol decreases peripheral conversion of T4 to T3 (mechanism unknown)
what kind of cell is most common in the pituitary vs. what kind of adenoma is most common
somatotrophs (GH secreting) are most common normally
prolactinomas are the most common pituitary tumor
what electrolyte (chem 7) differences would you expect between primary and secondary adrenal insufficiency
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
through what cytokine do thiazolidinediones exert their therapeutic effect and how
thiazolidinediones (aka glitazones) bind and upregulate PPAR-gamma (an intracellular nuclear receptor) which increases adiponectin (a cytokine) levels leading to decreased insulin resistance
in what kind of thyroid cancer would you see Hurthle cells (large cells with eosinophilic cytoplasm)
what form of hypothyroidism also shows Hurthle cells
follicular thyroid carcinoma;
Hashimoto’s thyroiditis
name two histologic features that differentiate papillary thyroid carcinoma from follicular thyroid carcinoma
papillary thyroid carcinoma has psammoma bodies (concentrically calcified structures) and ground glass, grooved nuclei
describe the molecular pathway by which insulin promotes glycogen synthesis
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
besides activating glycogen synthase, what else does protein phosphatase do (in regard to metabolic pathways)
protein phosphatase dephosphorylates and thereby inactivates F-1,6-BP, which is necessary for gluconeogensis
(so protein phosphatase inhibits gluconeogenesis)
what’s an easy way to differentiate between 21-hydroxylase and 11-beta-hydroxylase deficiency
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
what are three classic findings for glucagonoma
diabetes mellitus, necrolytic erythema and anemia
jejunal ulcers should make you think of what tumor
gastrinoma
what are the 3 ways that PTH increases serum calcium
- increases bone resorption through osteoclast activity
- increases gut absorption of calcium via activation of vitamin D
- increases Ca2+ reabsorption in the DCT
in patients with fructose intolerance what enzyme can allow for some fructose to still be metabolized for glycogen synthesis
hexokinase converts fructose to F-6-P, which can then be converted to glucose for glycogen synthesis or F-1,6-BP for glycolysis
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
type 1 DM;
test with fasting blood glucose
describe sensors that lead to ADH secretion
osmoreceptors in the hypothalamus and baroreceptors in the carotids and atria
how can you distinguish between central DI and nephrogenic DI
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)
delayed puberty plus anosmia is suggestive of what disease?
what is the etiology?
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
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
osteoporosis due to downregulation of GnRH which leads to decreased FSH and LH and thereby decreased estrogen, which is important for bone density
how does the hypothalamus regulate prolactin secretion
dopamine, secreted from the hypothalamus acts on D2 receptors in the lactotrophs to downregulate prolactin secretion
what is tachyphylaxis
tachyphylaxis (aka rapid drug tolerance) is decreased response to a drug after repeated administration
what is permissive effect (with regards to drug interactions)
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)
in the TCA cycle which steps produce NADH?
which produce FADH2?
which produce GTP?
- 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)
explain how pyruvate is converted to PEP in gluconeogenesis
- pyruvate is first converted to oxaloacetate by pyruvate carboxylase
- 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)
what are neurophysins
carriers of ADH and oxytocin that carry them from hypothalamus to posterior pituitary
what do acarbose and miglitol inhibit and where on the cell is it located
acarbose and miglitol treat T2DM by inhibiting alpha-glucosidase (a disaccharidase)
what is the medication of choice for treatment of gestational diabetes mellitus
insulin
why are non-selective beta blockers contraindicated in diabetes patients?
what kind of beta blocker could you use and why?
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
what embryologic process causes lingual thyroid
failure of the thyroid gland to migrate properly ==> sublingual thyroid that must be surgically removed to avoid asphyxiation
explain the metyrapone stimulation test
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
mononuclear infiltration with germinal centers and a diffusely enlarged thyroid on physical exam is characteristic of what thyroid disease
Hashimoto’s thyroiditis
what enzyme in the kidney converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
1-alpha-hydroxylase
from what cells does medullary thyroid carcinoma arise and what does it look like on histology with stain
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)
