Block 3 Week 5

Front 1

how are primidines absorbed/salvaged

Back 1

at the nucleoside level

Front 2

describe how dTTP is synthesized, from what precursor, and why in this method

Back 2

dUTP > dUMP > dTMP > dTTP; keep dUTP low because DNA polymerase cannot distinguish between dUTP/dTTP

Front 3

describe the effect of 5-fluoro-uracil

Back 3

used as an anti-cancer agent; 5FU salvaged to dUMP and inhibits thymidylate synthase, preventing synthesis of thymidine and inhibiting DNA synthesis in proliferating cells

Front 4

describe the mechanism of DHF reductase-inhibitors

Back 4

thymidine synthesis requires THF, and DHF recycled to THF, so lack of THF inhibits thymidine synthesis > inhibit DNA synthesis

Front 5

describe THF/B12 interaction in primary folate metabolic pathway

Back 5

THF donates group to B12 to make it active > active B12 donates CH3 group to homocysteine to make methionine > methionine can be converted to SAM

Front 6

what is the function of SAM

Back 6

methyl group donor, metabolic pathways

Front 7

what compound can build up with folate/B12 deficiency, what is the risk

Back 7

homocysteine; increased risk of CV disease

Front 8

list four anti-metabolite drugs

Back 8

1. acyclovir, 2. AZT, 3. cytosine arabinose, 4. 6-mercaptopurine

Front 9

which anti-metabolite can be used against HIV

Back 9

AZT (affects viral DNA polymerase)

Front 10

describe difference between anterior/posterior pituitary secretions

Back 10

posterior pituitary secretes oxytocin/vasopressin (ADH) from neurons; anterior pituitary secretes from its own cells under control by hypothalamus (secrete ACTH, FSH/LH/TSH, GH, prolactin)

Front 11

what is the precursor molecule for ACTH, what else can ACTH break down to

Back 11

POMC; ACTH and POMC can be broken down into MSH (melanocyte stimulating hormone) that can darken skin by stimulating melanocytes

Front 12

what are positive/negative releasing factors for GH (growth hormone)

Back 12

somatostatin inhibits; GHRH stimulates

Front 13

what are positive/negative releasing factors for FSH/LH, TSH

Back 13

GnRH and TRH

Front 14

what are positive/negative releasing factors for prolactin

Back 14

dopamine

Front 15

list two ways GH can exert its actions

Back 15

1. directly on tissue, 2. secondary pathway, producing IGF1

Front 16

what are primary effects of GH

Back 16

1. stimulating growth of long bones, 2. increase metabolic, cell proliferation, 3. stimulating osteoblast/osteoclast activity and proliferation

Front 17

how does long bone elongation occur

Back 17

GH stimulates chondrocyte proliferation and maturation > epiphyseal cartilage plate moves up and cartilage below is replaced with calcified bone (increased secretion of matrix)

Front 18

what are the three primary bone-related cells, and their origin

Back 18

1. chondrocyte (mesenchymal), 2. osteoblast (mesenchymal), 3. osteoclast (macrophage)

Front 19

list two causes of excessive GH

Back 19

1. tumor of pituitary/hypothalamus; 2. ectopic tumor, usually at lung

Front 20

two conditions that excessive GH can cause

Back 20

1. acromegaly -- occurs after closure of epiphyseal plate; thickening of skin, enlarged hands; 2. gigantism -- very tall, can lead to acromegaly

Front 21

define laron syndrome

Back 21

defect in GH receptor

Front 22

define idiopathic short stature

Back 22

normal GH levels, but insufficient for normal growth; can supplement with GH to grow taller

Front 23

two primary sources of GH deficiency

Back 23

1. congential, due to defect in GH/receptor/etc; 2. acquired, due to tumor/trauma

Front 24

describe pathogenesis of graves' disease

Back 24

hyperactive synthesis of TH, caused by antibody autoimmune reaction on TSHr

Front 25

what happens when TSH binds to thyroid

Back 25

1. stimulates insertion/synthesis of Na/I symporter channels; 2. increase synthesis of thyroglobulin; 3. increase thyroid peroxidase activity

Front 26

what is the primary amino acid in TH

Back 26

tyrosine

Front 27

what is thyroid peroxidase

Back 27

oxidizes iodine so it can be coupled with thyroglobulin

Front 28

describe pathway of TH synthesis

Back 28

1. TSH stimulates synthesis, 2. iodine is oxidized, 3. thyroglobulin and iodine are coupled, 4. stored as Tg-T4/Tg-T3, 5. secretion requires cleaving off Tg

Front 29

what is the primary thyroid hormone released

Back 29

T4 (thyroixine)

Front 30

characteristics of T3 vs T4

Back 30

T3 is more potent, but much shorter half-life than T4; in tissues T4 will be converted to T3

Front 31

describe activation/inactivate of thyroid hormone

Back 31

D1 (thyroid/liver) converts to T3 (regulated by T3); D2 (brain, other cells, pituitary) provides rapid T3 production; D3 -- for inactivation of T4 or inactivation of T3

Front 32

describe consumptive hypothyroidism

Back 32

hyperactivity of D3 > hyperactive inactivation of TH

Front 33

in what state is most of TH in bloodstream

Back 33

bound to thyroxine binding protein

Front 34

how is TH level regulated

Back 34

free T3/T4 inhibit secretion of TSH from the anterior pituitary gland (contains D2)

Front 35

how is thyroid hormone levels assessed

Back 35

TSH level, sometimes get T3/T4 assay

Front 36

what assays can be performed to assess graves' disease

Back 36

look for antibody against TSHr or thyroxine binding protein

Front 37

how does T3 exert its metabolic effects

Back 37

binds to thyroid response element to affect gene regulation

Front 38

pathogenesis of creatinism

Back 38

extreme hypothyroidism (iodine, gland) leading to mental retardation and failure to grow

Front 39

what is congential hypothyroidism

Back 39

defective thyroid (no thyroid gland) or defective TH

Front 40

what are signs of hypothyroidism (blood tests)

Back 40

elevated TSH, normal or low T3/T4; normal T3/T4 presented in subclinical hypothyroidism

Front 41

pathogenesis of hashimoto's disease

Back 41

autoimmune attack against thyroid cells, causing hypothyroidism

Front 42

how is hypothyroidism treated

Back 42

administration of T4, levothyroxine

Front 43

what are some clinical signs of graves' disease

Back 43

bug-eyed, sleep disturbance, tremors, goiter

Front 44

what is treatment for graves' disease

Back 44

anti-thyroid substances or surgery

Front 45

pathogenesis of subacute thyroiditis

Back 45

inflammation/destruction of follicles causes hyperthyroidism > hypothyroidism after TH is depleted > resolves on its own in most patients

Front 46

list two types of goiters

Back 46

1. cold nodules, hypofunctioning, should be removed; 2. hot nodules, hyperactive, but usually benign

Front 47

what is thiazide effect on calciium absorption

Back 47

increases calcium absorption

Front 48

describe Ca2+ transport in bloodstream

Back 48

half ionized form, half are protein-bound

Front 49

what are two mechanisms of Ca2+ regulation and sites of function

Back 49

1. PTH (affects kidney/bone), 2. 1,25(D) (affects absorption at intestine)

Front 50

where is Ca2+ sensor located

Back 50

on parathyroid gland and on kidney

Front 51

describe mechanism of Ca2+ sensing

Back 51

increase in free-Ca2+ > decrease PTH secretion; at the kidney, high Ca2+ will reduce absorption of Ca2+

Front 52

describe activating mutations of Ca2+ sensor

Back 52

cell thinks it is always high Ca2+ > leads to low PTH > hypocalcemia

Front 53

describe inactivating mutations of Ca2+ sensor

Back 53

feedback is dampened > PTH is high > 1. hypercalcemia in blood serum, 2. kidney retain Ca2+ because cannnot sense hypercalcemia, so low urine Ca2+

Front 54

list four functions of PTH

Back 54

1. bone resorption, 2. increase renal Ca2+ absorption, 3. decrease renal PO4- absorption, 4. increase formation of active 1,25(D)

Front 55

describe bone resorption mechanism of PTH

Back 55

PTH binds osteoblast > express RANKL ligand > activates osteoclast

Front 56

where is the site of renal PTH regulation

Back 56

distal tubule

Front 57

describe vitamin D metabolism

Back 57

sunlight UVB activates vitD > liver converts to 25(D) > kidney converts to 1,25(D), this step requires PTH > vitD binds to vitD receptor > modulates gene transcription > 1. increase intestinal Ca2+ absorption, 2. increase bone resorption

Front 58

how is vitamin D measured

Back 58

measure 25(D) form, calcidiol, because 1,25(D) calcitriol has short half-life

Front 59

describe body response to low Ca2+

Back 59

1. secretion of PTH, 2a. renal Ca2+/PO4 absorption change, 2b. increase 1,25(D) > increase intestinal absorption of Ca2+, 2c. increase bone resorption

Front 60

describe body response to low PO4

Back 60

1. increase 1,25(D), 2a. feedback to decrease PTH > decrease renal Ca2+ absorption, 2b. increse bone desorption, 2c. increase intestine PO4/Ca2+ absorption and renal PO4 reabsorption

Front 61

what are typical symptoms of hypercalcemia

Back 61

asymptomatic, thirst, constipation, renal stones

Front 62

three primary causes of hypercalcemia

Back 62

1. malignant bone tumor, secretes PTH-related peptide which functions similarly to PTH; 2. vitamind D intoxication; 3. renal reabsorption, due to familial hypocalciuric hypercalcemia OR thiazides

Front 63

what is PTH-related peptide

Back 63

required for normal bone development as a paracrine hormone, but tumors elevate blood [PTH-rp] to detectable levels

Front 64

explain cause for four levels high/low PTH vs high/low Ca2+

Back 64

1. high PTH/Ca2+ -- hyperparathyroidism; 2. high PTH, low Ca2+ -- PTH not working; 3. low PTH, high Ca2+ -- tumor secreted PTH-rp; 4. low PTH, low Ca2+ -- hypoparathyroidism

Front 65

describe pathogenesis of primary hyperparathyroidism

Back 65

overactive parathyroid gland; long-term will develop calcifications

Front 66

what effect does hypocalcemia have on nerves

Back 66

increases excitability

Front 67

what is trousseau sign

Back 67

contraction due to hypoxia and hypocalcemia; place BP cuff over arm to witness contracture of hand

Front 68

what is chvostek sign

Back 68

observation of hyperstimulation of the facial nerve due to hypocalcemia (tap on the side of head)

Front 69

what are symptoms of hypocalcemia

Back 69

trousseau sign, chvostek sign, seizures

Front 70

what are some causes of hypocalcemia

Back 70

1. low Mg2+ (need for PTH function and vitamind D function); 2. low or defective PTH; 3. renal failure (leads to high PO4 and low 1,25(D)); 4. high PO4 (lowers Ca2+ and inhibits 1,25(D) synthesis)

Front 71

classic sign of albright's hereditary osteodystrophy

Back 71

shortened 4th metacarpel, short stature

Front 72

how does presentation of a cervical hump occur

Back 72

osteoporosis causing bone loss in the spine

Front 73

what is the primary result of osteoporosis

Back 73

decreased bone mass and bone matrix, causing increased risk of vertebral and compression fractures

Front 74

describe pathogenesis of osteomalacia

Back 74

defective bone mineralization of osteoid, resulting in softening of bones; caused by deficient vitamin D

Front 75

define genu valgum and genu varus, in what pathology

Back 75

rickets, bowing of the legs inward and outward

Front 76

which gland secretes androgens in male/female

Back 76

male -- testes; female -- adrenal glands

Front 77

what is the precursor molecule for steroid hormone synthesis

Back 77

cholesterol

Front 78

describe how steroids exert their effects on cells

Back 78

steroid hormone diffuses into cytoplasm > binds cytoplasmic receptor > translocate to nucleus to bind DNA motifs

Front 79

describe general steroid synthesis

Back 79

1. adrenal cell lipase convert lipid/cholesterol esters to free cholesterol; 2. desmolase converts cholesterol to pregnenolone; 3. each cell has different enzyme to make different steroid

Front 80

describe what each region of the adrenal gland makes (outer to inner)

Back 80

1. zona granulosa : aldosterone; 2. zona fasciculata : cortisol; 3. zona reticularis : androgens/sex steroids (synthesize a precursor, then transported to gonads to be converted to testosterone/estrogen)

Front 81

describe synthesis, binding of cortisol, and sites of negative feedback

Back 81

1. hypothalamus secrete CRH > anterior pituitary secrete ACTH; 2. ACTH drives lipase/desmolase to secrete cortisol (zona fasciculata); 3a. cortisol binds to cytoplasmic glucocorticoid receptors > translocate into nucleus; 3b. negative feedback at hypothalamus and pituitary

Front 82

what are the primary effects of cortisol

Back 82

1. increases blood glucose/fatty acid; 2. increase protein catabolism and lipolysis

Front 83

describe pathogenesis of congenital adrenal hyperplasia

Back 83

defective 21-hydroxylase (most common) > a. no synthesis of aldosterone/cortisol, b. shunt to testosterone; effects -- ambigious genitalia in female, precocious puberty in males

Front 84

what happens to ACTH levels in congenital adrenal hyperplasia

Back 84

extremely high due to low cortisol

Front 85

what signal stimulates aldosterone synthesis

Back 85

angiotensin II

Front 86

describe synthesis and binding of aldosterone

Back 86

1. decreased BP stimulates release of renin; 2. converted to AngI and AngII; 3a. SMC vasoconstriction; 3b. stimulate synthesis of aldosterone; 4. binds to cytoplasmic mineralcorticoid receptors; 5. increase synthesis of Na+ channels

Front 87

explain effect of elevated cortisol on aldosterone

Back 87

cortisol can mind to same mineralcorticoid receptors

Front 88

how is cortisol degraded, how can pathology develop

Back 88

degraded by dehydrogenase; licorice/tobacco inhibits dehydrogenase, or defective dehydrogenase, leads to hyperstimulation of mineralcorticoid receptors > hypertension

Front 89

treatment options of defective cortisol dehydrogenase

Back 89

ACE inhibitor, aldosterone anatagonist, AngII antagonist

Front 90

explain pathway of GH synthesis and action

Back 90

1. GHRH stimulates GH synthesis/release, transported on GH-binding protein; 2a. bind to liver > secrete IGF and IGF-binding protein (endocrine), 2b. bind tissue > secrete IGF (autocrine); 3. bind to IGF receptor > growth

Front 91

what are negative feedback mechanisms for GH synthesis

Back 91

GH inhibits GH release; GH stimulates somatostatin release, which inhibits GH release

Front 92

what are metabolic effects of GH

Back 92

increased amino acid uptake; increased protein/DNA/RNA synthesis; decreased glucose uptake