Endocrine Week One SAQ Study Guide Questions

ENDOCRINE WEEK ONE SAQ ST UDY GUIDE QUEST IONS 1. a. Describe how the entry of glucose stimulates insulin release. (2 marks) b. name the THREE antibodies made in T1DM. (1.5 marks) Answer: a. Glucose enters beta cells via GLUT 2 transporters. When it enters it undergoes anerobic and aerobic metabolism and then goes through the Kerb’s cycle which will increase ATP synthesis, and thus increase ATP levels. This will cause the closure of ATP dependent K+ channels. This will cause K+ to stay within the beta cells and not exist and rather build up within. As a result, this will increase the membrane potential pulling to the potential membrane potential. This will cause the opening of voltage gated Ca2+ channels. When Ca2+ will enter, it will bind onto SV2R on insulin vesicles, causing the snare proteins on the vesicles to link with the snare proteins found on the cell membrane, and consequently, mediate the fusion of the vesicle and the release of insulin out of the beta cell via exocytosis. b. Anti-islet, anti-insulin and anti-GAD antibodies. a. b. c. d. 2. Describe the synthesis of aldosterone (3 marks). Explain the action of aldosterone (3 marks). Damage to which part of the adrenal gland affects alderstone production? (0.5 marks). Explain the mechanism of action of fludrocortisone. (2 marks). Answer: a. Cholesterol -> pregnenolone -> progesterone -> 17-OH-progestrone -> corticosterone -> alderstone. b. Increase Na/K+ ATPase in the DCT and CT -> increase Na+ reabsorption -> water follows as Na+ is osmotically active -> increase blood pressure. It also decreases k+ excretion into the urine. c. Zona glomerulosa. d. It is an aldosterone receptor agonist. It acts to increase epithelial Na+ and K+ channels on the apical side of the tubules of the DCT and CT increases Na+/K+ ATPases on the basolateral side of the tubules of the DCT and CT. this will allow for increased Na+ reapportion into the blood stream and increased K+ excretion into the lumen of the nephrons which will get excreted in urine. 3. a. Compare the difference between an exocrine and endocrine gland and give examples of each. (2 mark). b. Describe the THREE main modes of the endocrine system. (3 marks). Answer: • • Exocrine: secrete hormones though ducts opening on to an external or an internal body surface. For example, pancreatic acini and gastric secretion. Endocrine: secrete hormones directly into the blood stream. For example, parathyroid glands, thyroid glands, pancreatic islet, gonads, parathyroids. 4. Compare the mode of action of peptide and steroid hormones and give ONE example of each. (2 marks). Answer: • • Peptide hormones such as TSH work on receptors bind onto receptors located on the outside surface of the cell to induce a secondary intercellular event. This means that they indirectly affect the DNA to affect gene expression. Steroid hormones are lipid soluble so they are able to cross the phospholipid membrane of the cell and bind onto intercellular receptors, that will then translocate to the nucleus and induce direct changes to the DNA to affect gene expression. 5. Name the cell that each of the following hormones acts on? a. TSH (0.5 mark) b. CRH (0.5 mark) c. FSH (0.5 mark) d. LH (0.5 mark) e. PRL (0.5 mark). f. Oxytocin (0.5 mark) Answer: a. b. c. d. e. f. Thyroid follicular cells to make thyroid hormones. Fasciculata and rectularis of the adrenal cortex to make corticosteroids. Ovarian follicular cells. Ovarian follicular cells. Mamillary glands. Uterus and breasts. 6. Describe the role of the hypothalamus and the pituitary in heat regulation (3 marks). 7. What are the differences between Liothyronine and Levothyroxine. (3 marks). Answer: • • Liothyronine is a synthetic T3 that is given orally. It is longer acting but less potent. It acts directly on the cell. Levothyroxine is a synthetic T4 that is given intravenously. It is shorter acting but more potent. It gets converted into T3. 8. Aisha is a 23-year-old female. She is 6 weeks pregnant. She presents with tachycardia, increased respiratory rate, hypertension and she look dehydrated. She tells you that she has been having diarrhea more often. You suspect that she has hyperthyroidism. (22 marks). a. Describe the steps of thyroid hormone synthesis. (10 marks). b. What is the most common cause of hyperthyroidism. Explain its’ pathogenesis. (2 marks) c. What is the difference between primary, secondary, and ectopic hyperthyroidism. Explain this using examples and comment on which of this is more common. (3.5 marks). d. Name the two commonly used medications for hyperthyroidism. (1 mark). e. Using you answer in part a) explain how these medications work and note their differences in the mechanism of action. (2.5 marks). f. Which of the two drugs in part d) is best for Aisha? (Justify your answer). (1 mark). g. Two years later Aisha returns, and she has arrhythmias. What medication should you avoid and why? (2 marks) h. If she was to develop bipolar disease, what drug should you avoid? (0.5). i. Explain how radioactive iodine 131 acts in the management of hyperthyroidism. (1.5 marks) j. What defines subclinical hyperthyroidism and what define subclinical hypothyroidism? k. Describe the rationale behind using thyroglobulin as a diagnostic tool. (2 marks). Answer: a. 1. In the hypothalamus, the paraventricular nucleus releases TRH, which then travels through the hypophyseal portal system into the anterior pituitary. 2. There it will act on thyrotropes by binding onto Gs coupled receptors. This will cause the activation of Gs -> AC -> covert ATP into cAMP -> PKA -> phosphorylation of transcription factors in the genes of the nucleus -> transcription of DNA to form mRNA which is then translated into proteins. PKA will also act to increase Ca2+ -> binds to SV2R on thyroid hormone vesicles -> linkage of snare proteins of the vesicle with the cell membrane -> vesicle fusion -> thyroglobulin colloid release. 3. From food we get iodine which is negatively charged and circulates in the blood in this form. This usually concentrates in the thyroid and is found in little concentrations in the blood. It gets into the cell via Na+/I- exchanger in exchange for Na+. 4. To excrete I- into the thyroid lumen from the thyroid cell, it gets pumped out via the pendrin protein. 5. In there it will get converted to neutral I2, thyroid peroxidase, which causes the loss of an electron (reduction reaction). 6. Thyroid peroxidase will take four of I2 and add two of each on two thyroglobulin on the thyroglobulin colloid or add 2 onto one and 1 onto one. This process is known as iodination. 7. These will the fuse. The ones with two one each form T4 and the ones with one with 2 and the other with 1. Will form T3. 8. These then get endocytosed into follicle thyroid cells via clathrin mediated endocytosis, which means that they get endocytosed into the form of a vesicle. 9. The vesicle will then fuse with lysosomal enzymes, which will isolate t3 and t4 from the thyroglobulin colloid, into a separate vesicle. 10. This new vesicle will then fuse with the cell membrane, and then be exocytosis into the blood. b. The most common cause is Grave’s Disease. This is a form of primary cause this is a thyroid gland issue. This is an autoimmune disease, where there is a mutation in the HLA-B8 gene, where there will be a production of TSH antibodies. These will act on TSH receptors found on follicular thyroid cells and cause excessive release of thyroid hormones. This disease is typically more common in women. c. Primary hyperthyroidism this is when the issue is due with the thyroid gland itself. For example, when there is a mutation in the follicular cells of the thyroid, causing them to uncontrollably divide and thus make massive thyroid hormone. Secondary, is when the issue is to do with the pituitary gland. For example, when there is a pituitary adenoma, causing an increase in thyrotrope synthesis and thus increased TSH release. Ectopic, this is when a site that is not meant to make thyroid hormones, makes them. For example, in small cell lung carcinoma. d. Propylthiouracil and methimazole. e. Both of these work on the thyroid lumen by inhibiting thyroid peroxidase. This means that there will be decreased iodination of the thyroid globulin colloid, so there will be less T3 and T4 synthesis. However, an additional feature of Propylthiouracil is that it acts on peripheral tissue by inhibiting 5’-deiodinase which will prevent the conversion of T4 into T3, which is means that there will, be less thyroid hormone in the active form. f. Aisha should be given Propylthiouracil, because in the first trimester this is when organogenesis of the foetus happens, and methimazole is very likely to cause damage to this if given in the first trimester of pregnancy. g. K+ channel blockers such as amiodarone should be avoided. This is because it can damage the thyroid follicular cells, which will cause a transient hyperthyroidism and then cause hypothyroidism. h. Lithium i. When it is administrated after a week it will accumulate within the colloid in the thyroid gland. The colloid is surrounded by thyroid cells. When it accumulates it releases beta radiation which causes damage to the thyroid cells as it kills them. j. Sub-clinical hyperthyroidism is when TSH is elevated but T3 and T4 are normal, and sub-clinical hypothyroidism is when TSH is decreased but T3 and T4 are normal. k. Thyroglobulin is measure in functional tissue. Ather thyroidectomy via ablation this should not be there or very low. If this goes up, this means that there is re-occurrence of the tumor or that some of the tumor is still there. l. . However, it cannot be used as a diagnostic tool for thyroid pathologies involving antibodies.