Term
| Which of the following are risk factors for osteoporosis -Cigarettes, alcoholism, low calcium intake, inactive lifestyle, prolonged premenopausal amenorrhea, early menopause, age, low body mass? |
|
Definition
|
|
Term
| There are two type of bone - trabecular(cancellous) and cortical(compact) - which type is more axial, active metabolically, and the first site of osteoporosis? |
|
Definition
|
|
Term
| True or False: in osteoporosis, resorption exceeds bone formation and the ratio of mineral to matrix is decreased. |
|
Definition
| False, resorption exceeds formation but the mineral to matrix ratio is the same. |
|
|
Term
| The end product hormones from the HPE Axes such as cortisol, T3/T4, IGF-1, Androgens, have a negative feedback mechanism affecting which of these: pituitary gland or hypothalamus? |
|
Definition
| Trick question, they negatively feedback on both |
|
|
Term
| Why do babies with metabolic diseases appear well until the end of their first week? |
|
Definition
| They are protected by maternal enzymes in utero until toxic byproducts accumulate |
|
|
Term
| In an infant that is ill, has normal blood pressure, unresponsive to acidemia management, sterile cultures, ketoacidemia, and is unresponsive to antimicrobial therapy allows you to rule out what possibility? |
|
Definition
|
|
Term
| When looking at possible genetics of a disease of an inborn error of metabolism, which usually has a negative family history, what should you look for to signal an autosomal recessive disease versus an x-linked recessive disease? |
|
Definition
| AR- negative family history, but look for consanguinity (genetic closeness of parents); XLR - positive family history in uncles and nephews |
|
|
Term
| You should consider metabolic diseases in neonates with presumed sepsis or acidosis and in any child with a Reye-like illness, but what are the features of Reye’s? |
|
Definition
| non-inflammatory encephalopathy with elevated circulating transamidases and ammonia, often associated with hypoglycemia |
|
|
Term
| In the management of metabolic disorders you must remove the offending metabolites via hemodialysis and modify diet, why does simple vitamin supplementation work for some disorders? |
|
Definition
| Vitamins are used as cofactors by many enzymes for their reactions and they may be responsive to supplementation, like biotin for biotinidase deficiency and thiamine for MSUD |
|
|
Term
| Which of the following are physical findings of metabolic diseases - acidemia, sweet or unusual odors, abnormal hair, hyperammonemia, rashes, intractable seizures, alopecia, or complex metabolic aciduria? |
|
Definition
|
|
Term
| What are the symptoms of acute metabolic disease? |
|
Definition
| nonspecific with poor feeding, irritability, lethargy, vomiting progressing to seizures, coma, apnea |
|
|
Term
| GH, known for its direct effects on tissues as well as indirect actions like the induction of insulin-like growth factor at target tissues, can increase longitudinal growth and metabolic activities but what are 3 factors that modify its effects? |
|
Definition
| Target tissue, duration of action, and whether the body is in an anabolic or diabetogenic state |
|
|
Term
| GH effects bones by increasing longitudinal growth at the epiphyseal cartilage plate before it closes by inducing what? |
|
Definition
| Chondrocyte proliferation and secretion of matrix proteins |
|
|
Term
| There are two types of bone formation- intramembranous and endochondral- which utilizes osteoblasts only and which uses both osteos and chondroblasts? |
|
Definition
| IM uses osteos only, Endochondral uses both |
|
|
Term
| Excess GH secretion caused by pituitary/hypothalamic or ectopic tumors cause acromegaly and gigantism, what is the difference between the two? |
|
Definition
| Acro causes thickening of skin and enlargement of organs/skeleton, and so does gigantism except that it occurs before closing of the epiphyseal plates |
|
|
Term
| What are the specific differences between congential and acquired GH deficiency? |
|
Definition
| Congenital - defect of GH/GHRH/IGF or GH receptor including developmental abnormalities of the pituitary; acquired - tumors, pituitary trauma, psychosocial depravation |
|
|
Term
| True or False: GH release is constant thru the day. |
|
Definition
| False, is pulsatile and there is high release at night |
|
|
Term
| Why is it that GH is so cheap to produce from bacteria? |
|
Definition
| Because the molecule is a single polypeptide chain with no carb groups so that it is excreted in its active form by DNA recombinant bacteria |
|
|
Term
| True or False: IGF inhibits GH release and also stimulates somatostatin release. |
|
Definition
|
|
Term
| What pathway does GH activate using tyrosine kinase cell receptors to increase metabolism and proliferation? |
|
Definition
|
|
Term
| What type of these metabolic activities does GH perform in the long term, either insulin-like or anti-insulin like? |
|
Definition
| Both, that is why it can lead to decreased glucose uptake and molecular homologues can cause gestation diabetes |
|
|
Term
| When GH binds to its receptor in in the liver and other target tissues, the resulting molecule that is created is called IGF, which of these functions can it perform - autocrine, paracrine, endocrine? |
|
Definition
|
|
Term
| What is the role of soluble forms of GH and IGF receptors called binding proteins? |
|
Definition
| They bind their respective molecules to decrease degradation and maintain circulating levels of hormone |
|
|
Term
| True or False: IGF-1, which functions in both prenatal and postnatal growth, binds to receptors similar to insulin receptors, but cannot activate insulin receptors themselves. |
|
Definition
| False, they can bind to insulin receptors. |
|
|
Term
| When iodine is transported into thyroid cells via the Na/I symporter, what role does it play it the creation of thyroxine (T4) and triiodothryonine (T3)? |
|
Definition
| It becomes bound to the thyroglobulin colloid at the apical surface, then the Tg-I converts to a Tg-T4-T3 complex via thyroid peroxidase to be absorbed by the cell. |
|
|
Term
| Although the majority of hormone created by a thyroid cell is T4, what enzymes cleave the extra iodine to convert it to the most abundant thyroid hormone, T3, and where do they exist? |
|
Definition
| Deiodinase 1 and 2; aka D1 is found in the thyroid, liver, and kidney; and D2 is in the thyroid, brain, pituitary and brown adipose tissue |
|
|
Term
| True or False: T3/T4 in the blood mostly exists as free unbound hormone in the blood, but sometimes binds to thyroxine binding globulin and albumin. |
|
Definition
| False, it rarely exists unbound in blood and is usually bound to those proteins. |
|
|
Term
| What percentage of daily T3 production is extra-thyroidal? |
|
Definition
| 80%, the majority of which is made by D2 in the thyroid, pituitary, skeletal, and cardiac muscle. |
|
|
Term
| TSH regulation is highly sensitive to what unbound molecule in the plasma? |
|
Definition
|
|
Term
| _________ assay is the optimal screening test in ambulatory healthy patients for thyroid malfunction. |
|
Definition
| TSH, where high TSH indicates hypothyroidism, and low equals hyper... |
|
|
Term
| What is T3’s role in DNA transcription rates? |
|
Definition
| In the presence of T3 hormone DNA transcription increases because it binds to the activator proteins |
|
|
Term
| True or False: Maternal and fetal iodine deficiency severely retards growth and brain formation of children, known as cretinism. |
|
Definition
|
|
Term
| If a person has a mutated MCT8 transfer protein in their neurons then they can’t absorb the necessary ________ for development. |
|
Definition
|
|
Term
| What has a greater prevalence in the population, hypo or hyperthyroidism? |
|
Definition
| Hypo, with mild being the highest level seen. |
|
|
Term
| Which of these are clinical signs of hypothyroidism - bradycardia, course hair, dry/pale skin, goiter, delayed relaxation of deep tendon reflexes? |
|
Definition
| All; treatment with lexothyroxine is the treatment of choice. |
|
|
Term
| What is the most common cause of hyperthyroidism? |
|
Definition
| Grave’s disease, which is the result of auto-antibodies bind to TSH receptors and chronically stimulating it; treatment is radioiodine or antithyroid drugs |
|
|
Term
| Which of these sign reveal hyperthyroidism - goiter, tachycardia, tremor, palpitations, heat intolerance, or sleep disturbance? |
|
Definition
|
|
Term
| What is the cause of Grave’s disease opthalmopathy? |
|
Definition
| Proliferation of fibroblasts causing edema behind eyes, probably due to inflammatory cytokines released in response to thyroid antigen |
|
|
Term
| If you are stuck, how do you differentiate between Grave’s disease and thyroiditis? |
|
Definition
| Radioiodine uptake; if low it thyroiditis because autoimmune response destroys thyroid cells, if high its graves because the antibodies stim the cell to over-secrete hormones |
|
|
Term
| True or False: resistance to thyroid hormone is due to mutation of the thyroid hormone receptor beta gene causing elevated T4/T3 and normal TSH. |
|
Definition
|
|
Term
| 90% of nodular goiters are ____________ (hypo/hyperfunctioning) |
|
Definition
| hypofunctioning or “cold” |
|
|
Term
| What percent of hyperfunctioning “hot” nodular goiters are benign and need to be aspirated? |
|
Definition
| 99% benign, don’t need to be aspirated; cold nodules do need aspiration |
|
|
Term
| What percentage of bone is mineral phase (made of hydroxyapatite) and what percent is organic matrix (made of collagen)? |
|
Definition
|
|
Term
| Arrange the following minerals in order from greatest amount in the body to least - magnesium, phosphorus, calcium. |
|
Definition
| Calcium, phosphorus, magnesium |
|
|
Term
| True or False: The distribution of calcium and phosphorus in plasma is equally split between ionized and protein bound for both molecules. |
|
Definition
| False, calcium is approx equal in plasma, but phosphorus is 80% ionized and 15% protein bound |
|
|
Term
| Which of the following are physiological uses for phosphorus - mineralization, metabolism intermediary (phosphorylation), intracellular pH buffer, chemical energy (ATP)? |
|
Definition
|
|
Term
| What are the principal hormones regulating calcium and phosphorus metabolism in the body? |
|
Definition
| Parathyhroid (kidney, bone) and Vitamin D (intestine) |
|
|
Term
| How does a parathyroid cell detect plasma calcium levels and would it affect it’s release of PTH if it detects calcilytics or calcimimetics? |
|
Definition
| It has a Calcium sensing receptor on the cell membrane; if it senses calcilytics it increases PTH, if it senses calcimimetics it would decrease PTH |
|
|
Term
| How does PTH increase osteoclast proliferation and activity? |
|
Definition
| PTH bind with osteoblasts causing them to release M-CSF which induces osteoclast precursors to mature and become active. RANK receptors on osteoblasts also can then bind with osteoclasts increasing activity. |
|
|
Term
| Which of these are the principal actions of PTH - increase bone resorption of Ca and PO4, increase renal reabsorption of Ca while decreasing amount of PO4, increase renal formation of vitamin D? |
|
Definition
|
|
Term
| What portion of the nephron absorbs the most Ca and which part is responsive to PTH? |
|
Definition
| Proximal tubule absorbs 65%, and the distal tubule responds to PTH absorbing 5-10% |
|
|
Term
| As serum vitamin D levels increase, PTH levels __________. |
|
Definition
|
|
Term
| Describe how vitamin D augments calcium and phosphate resorption and reabsorption. |
|
Definition
| Vitamin D is modified by the liver 25OH-d and kidneys 1,25(OH)2D, its metabolite induces Ca channel increases in the small intestine and it promotes osteoclast maturation (with PTH). |
|
|
Term
| If a person is hypocalcemic describe how the body responds so that there is a net retention of Ca, and no net effect on phosphorus. |
|
Definition
| There is an increase in PTH which also elicits increase in vitamin D; PTH raises renal Ca, drops renal PO4 while vitamin D raises intestinal Ca and PO4 absorption; the two act together on bones to raise skeletal Ca and PO4 resorption |
|
|
Term
| If a person is hypophosphatemic describe how the body responds so that there is a net retention of phosphorus, and no net effect on calcium. |
|
Definition
| Vitamin D increases which decreases PTH; Vitamin D acts to increase renal PO4, intestinal Ca and PO4, and skeletal Ca and PO4, while PTH decreases renal Ca absorption |
|
|
Term
| True or False: Patients with primary hyperparathyroidism have hypocalcemia with no symptoms and 80-85% originate from solitary adenomas. |
|
Definition
| False, these patients have hypercalcemia, the rest is true. Hypercalcemia normally causes no symptoms but it can cause gastro or genito upset. |
|
|
Term
| Humoral hypercalcemia of malignancy consists of 80% hypercalcemias induced by cancer due to what hormonal agent that is secreted by the cancer? |
|
Definition
|
|
Term
| What are the actions of parathryroid hormone related peptide that is released by the cerebellum? |
|
Definition
| Bone development, promotes proliferation and inhibits apop for chondrocytes, induces breast development and lactation |
|
|
Term
| What are the clinical findings of hypocalcemic pseudohypoparathyoirdism? |
|
Definition
| Biochemical hypoparathyroidism with hypocalcemia and hyperphosphatemia but with elevated PTH secretion and end-organ resistance to PTH; there is also a hereditary component that is autosomal dominant resulting in hereditary osteodystrophy |
|
|
Term
| Which of the following are symptoms of hypocalcemia - laryngeal spasm, seizures, papillaedema, prolonged QT, hyperreflexia? |
|
Definition
|
|
Term
| Which of these are possible causes for hypocalcemia - low albumin, chronic renal failure, Mg deficiency, pseudo/hypoparathyroidism, hyperphosphatemia, osteomalacia with Vit. D deficiency? |
|
Definition
|
|
Term
| What is the most common type of fracture for osteoporosis which is characterized by microarchitectural deterioration of bone tissue? |
|
Definition
|
|
Term
| Which of these can be secondary causes of osteoporosis - failure to develop normal skeleton mass or endocrine deficiency/excess? |
|
Definition
| Both; endocrine problems can stem from cushing's, androgens, hyperthyroid, glucos, hyperparathyroid |
|
|
Term
| Osteomalacia and rickets can be defined as unmineralized osteoid due to impaired mineralization, what are the clinical features? |
|
Definition
| Vitamin D or phosphate deficiency, decreased intestinal Ca absorption, skeletal PTH resistance, secondary hyperparathyroidism |
|
|
Term
| What is the function of bisphosphonate drugs on bones? |
|
Definition
| Reduces osteoporotic fractures by inhibiting osteoclast function |
|
|
Term
| Do thiazide diuretics reduce hip fractures in osteoporotic patients? |
|
Definition
| No; they should only be allowed if a patient is also hypertensive. |
|
|
Term
| Since steroid hormones are endocrine and enter all cells why is it that they only activate certain cells? |
|
Definition
| Because cells must have the necessary nuclear receptor (soluble proteins) in their cytosol to activate specific genes once they diffuse through the membrane |
|
|
Term
| What is the difference in how steroid hormones(cortisol) and protein hormones(insulin) affect change in a cell? |
|
Definition
| Steroids diffuse through the membrane activating nuclear receptors directly, whereas protein hormones must activate cell surface proteins to conduct a signaling pathway to affect change |
|
|
Term
| Which part of the adrenal gland synthesizes catecholamines and which part makes aldosterone, cortisol, and androgens? |
|
Definition
| Catecholamines=medulla; zona glumerulosa=mineralo, fasciculata=gluco, reticularis=androgens |
|
|
Term
| When synethsizing steroid hormones there are two enzymes that are critical to the process and are regulatory control points, what are they? |
|
Definition
|
|
Term
| Which of the following are the major effects of cortisol - increases blood glucose (gluconeogenesis) and FFA, promotes protein catabolism and lipolysis, anti-inflammatory, euphoria? |
|
Definition
|
|
Term
| What would happen to the feedback mechanism in steroid synthesis if a key enzyme, like 21-hydroxlase, were deficient? |
|
Definition
| There would be no negative feedback so there would be an increase in hormones from the pituitary and you would have excessive hormone intermediates, eg Congential Adrenal Hyperplasia |
|
|
Term
| What disease state does this describe: adrenal or pituitary tumor producing excess cortisol, rounded face, obesity, steroid diabetes, HTN, weakened bones? |
|
Definition
|
|
Term
| True or False: Type I congenital adrenal hyperplasia accounts for 90% of CAH and is the result of a defect in 21-hydroxylase, which leads to high ACTH because of reduced feedback and high levels of intermediates converted to androgens. |
|
Definition
|
|
Term
| Considering the fact the MR, mineralocorticoid receptor, binds with both aldosterone (it’s normal moiety) and cortisol and cortisol is present in the plasma at 1000x> aldosterone, what keeps the MR from hyperactivity? |
|
Definition
| Cortisol is converted to inactive cortisone by the steroid dehydrogenase in cells; that’s why blocking that enzyme can cause hypertension due to excess Na channels being created in the distal tubule. |
|
|
Term
| True or False: LH induces leydig cells to secrete testosterone which, when bound to a target cell, partly activates an androgen receptor and also gets converted by 5-a-reductase to DHT which binds a different androgen receptor. |
|
Definition
|
|
Term
| What is induced by testosterone versus its analogue DHT? |
|
Definition
| Testosterone induces spermatogenesis, gonadotropin regulation, and sexual differentiation; DHT induces external virilization and maturation (so a 5-a-reductase deficiency causes incomplete virilization in males). |
|
|
Term
| Which organ is the primary(indirect) source of estrogens in post-menopausal women? |
|
Definition
|
|
Term
| In the creation of estrogen LH induces theca cells to create androgens which granulosa cells, activated by FSH, utilize to make estrogen by utilizing what key enzyme? |
|
Definition
|
|
Term
| How do you calculate LDL? or VLDL? |
|
Definition
| LDL=Total-(HDL+VLDL); VLDL=TG/5 |
|
|
Term
| Which of the following is bone remodeling influenced by - steroid hormones, thyroid hormones, rheumatoid arthiritis, T1DM, hematologic disorders? |
|
Definition
|
|
Term
| What are the end effects of glucocoritcoids versus thyroxines? |
|
Definition
| Gluco - gluconeogenesis, immune-modulation, vascular response to catecholamines; T3/T4 - skeletal growth, O2 consumption, nutrient utilization, thermogenesis, protein synthesis. |
|
|
Term
| How does magnesium deficiency relate to renal PTH response? |
|
Definition
| Low Mg cause a renal resistance to PTH, so there is less Ca absorbed. |
|
|
