Endo - Physiology (Thyroid & Parathyroid) Flashcards
Pg. 314-315 & 316 in First Aid 2014 or 293-294 & 295 in First Aid 2013 Sections include: -PTH -Calcium homeostasis -Vitamin D (cholecalciferol) -Calcitonin -Thyroid hormones (T3/T4)
What is the source of PTH?
Chief cells of parathyroid
What 4 major functions does PTH have?
(1) Increase bone resorption of calcium and phosphate (2) Increase kidney reabsorption of calcium in distal convoluted tubule (3) Decrease reabsorption of phosphate in proximal convolute tubule (4) Increase 1,25-(OH)2 D3 (calcitriol) production by stimulating kidney 1alpha-hydroxylase
What effect does PTH have on serum and/or urine levels of Ca2+ and (PO4)3-?
PTH increases serum Ca2+, decreases serum (PO4)3-, and increases urine (PO4)3-
Again, what function does PTH have with regard to bone? What is the mechanism behind this function?
Increase bone resorption of calcium and phosphate; Increased production of M-CSF and RANK-L (receptor activator of NF-kappaB ligand). RANK-L (ligand) secreted by osteoblasts & osteocytes binds RANK (receptor) on osteoclasts & their precursors –> osteoclast stimulation and increased Ca2+
What effect does PTH have on phosphate (PO4)3- levels in the serum and urine? What is a good way to remember this?
PTH decreases serum phosphate and increases urine phosphate; Think: “PTH = Phosphate Trashing Hormone”
What are the 3 methods for regulation of PTH based on serum levels, and what effect(s) do they have on PTH secretion?
(1) Low serum Ca2+ –> Increased PTH secretion (2) Low serum Mg2+ –> Increased PTH secretion (3) Very low serum Mg2+ –> Decreased PTH secretion
What is PTHrP? In what conditions is it commonly increased?
PTH-related peptide (PTHrP) functions like PTH & is commonly increased in malignancies (e.g., paraneoplastic syndromes)
What effect do low and very low serum Mg2+ have on PTH secretion?
Low serum Mg2+ –> Increased PTH secretion; Very low serum Mg2+ –> Decreased PTH secretion;
Again, what effects do low and very low serum Mg2+ have on PTH secretion? What are 4 common causes of low Mg2+?
Low serum Mg2+ –> Increased PTH secretion; Very low serum Mg2+ –> Decreased PTH secretion; Common causes of low Mg2+ include diarrhea, aminoglycosides, diuretics, and alcohol abuse
Draw a visual to depict calcium homeostasis, include explanations of the involvement of the following key players in this process: (1) Low ionized calcium (2) Parathyroid glands (3) Renal tubular cells (4) Bone (4) Intestines.
See p. 314 in First Aid 2014 for visual at bottom left
Draw a visual to depict phosphate homeostasis, include explanations of the involvement of the following key players in this process: (1) Low serum phosphorus (2) Renal tubular cells (3) Bone (4) Intestines.
See p. 314 in First Aid 2014 for visual at bottom right
What are 2 types of negative feedback on PTH?
(1) Production of 1,25-(OH)2D3 (by renal tubular cells in response to PTH) –> feedback inhibition of PTH synthesis (on parathyroid glands) (2) Increases in serum calcium (by bone/kidney responses to PTH) –> feedback inhibition of PTH secretion
What are 3 forms in which plasma Ca2+ exists, and what percentage is each of these forms?
Plasma Ca2+ exists in 3 forms: (1) Ionized (~45%) (2) Bound to albumin (~40%) (3) Bound to anions (~15%)
How does an increase in pH affect Ca2+? What is the source of clinical manifestations, and what are 4 examples of clinical manifestations?
Increase in pH => Increased affinity of albumin (negative charge) to bind Ca2+ => clinical manifestations of hypocalcemia (cramps, pain, paresthesias, carpopedal spasm)
What is another name for Vitamin D?
Vitamin D (cholecalciferol)
What are two sources of Vitamin D? To what forms are both converted, and where? Which form is active?
D3 from sun exposure in skin. D2 ingested from plants; Both converted to 25-OH in liver and to 1,25-(OH2) (active form) in kidney
What are 2 functions of Vitamin D?
(1) Increases absorption of dietary Ca2+ and (PO4)3- (2) Increases bone resorption –> increased Ca2+ and (PO4)3-
What are 4 regulators of Vitamin D, and how does each accomplish their regulation?
(1) High PTH (2) Low [Ca2+] (3) Low (PO4)3- (all) cause increased 1,25-(OH)2 production (4) 1,25-(OH)2 feedback inhibits its own production
What does Vitamin D (cholecalciferol) deficiency cause in kids versus adults?
Deficiency causes rickets in kids and osteomalacia in adults
What are 4 causes of Vitamin D (cholecalciferol) deficiency?
Caused by (1) malabsorption (2) low sunlight (3) poor diet (4) chronic kidney failure
Name an inactive form of vitamin D, besides 25-OH D2 or D3.
24,25-(OH2) D3 is an inactive form of vitamin D
Explain the difference in effects of PTH versus 1,25-(OH)2 (vitamin D) in terms of Ca2+ and (PO4) 3- reabsorption/absorption.
PTH leads to increased Ca2+ reabsorption and decreased (PO4)3- reabsorption in the kidney, whereas 1,25-(OH)2 leads to increased absorption of both Ca2+ and (PO4)3- in the gut
What is the source of calcitonin?
Parafollicular cells (C cells) of thyroid
What is the function of calcitonin?
Decreased bone resportion of Ca2+; Think: “calciTONin TONes down Ca2+ levels”
What regulates calcitonin?
Increased serum Ca2+ causes calcitonin secretion
What role does calcitonin play in Ca2+ homeostasis?
Calcitonin opposes action of PTH. Not important in normal Ca2+ homeostasis.
What are the thyroid hormones? What do they contain, and what (in general) do they control?
Thyroid hormones (T3/T4); Iodine-containing hormones that control the body’s metabolic rate
What is the source of thyroid hormones (T3/T4)? Where is most T3 formed?
Folicles of thyroid. Most T3 formed in target tissues.
What are the 5 major functions of thryoid hormones (T3/T4)?
(1) Bone growth (synergism with GH) (2) CNS maturation (3) Increase Beta1 receptors in heart = increased CO, HR, SV, contractility (4) Increase basal metabolic rate via increased Na+/K+ ATPase activity = increase O2 consumption, RR, body temperature (5) Increase glycogenolysis, gluconegoenesis, lipolysis; Think: T3 Functions - “4 B’s: Brain maturation, Bone growth, Beta-adrenergic effects, Basal metabolic rate increase”
What is TBG, and what role does it play? How does this role effect hormone activity?
Thyroxine-binding globulin (TBG) binds most T3/T4 in blood; only free hormone is active
What is a condition in which TBG is decreased? In what context/conditions is TBG increased?
Low TBG in hepatic failure; High TBG in pregnancy or OCP use (estrogen increases TBG)
Of T3 and T4, which is the major thyroid product? How is the other derived, and where?
T4 is major thyroid product; converted to T3 in peripheral tissue by 5’-deiodinase
Contrast T3 and T4 in terms of affinity.
T3 binds receptors with greater affinity than T4
In terms of the thyroid, what roles do peroxidase play?
Peroxidase is enzyme responsible for oxidation and organification of iodide as well as coupling of monidotyrosine (MIT) and diiodotyriosine (DIT)
What is the mechanism of Propylthiouracil versus Methimazole?
Propylthiouracil inhibits both peroxidase and 5’-deiodinase; Methimazole inhibits peroxidase only
What are 3 methods of regulation on thyroid hormones?
(1) TRH (hypothalamus) stimulates TSH (pituitary), which stimulates follicular cells (2) Negative feedback by free T3, T4 to anterior pituitary decreases sensitivity to TRH (3) Thyroid-stimulating immunoglobulins, like TSH, stimulate follicular cells (e.g., Graves disease)
What is the Wolff-Chaikoff effect?
Wolff-Chaikoff effect - excess iodine temporarily inhibits thyroid peroxidase => low iodine organification => low T3/T4 production
Draw a diagram depicting the major processes occurring in the follicular cell versus its surrounding blood and lumen. Indicate where Anions (perchlorate, pertechnetate, thiocyanate) versus Antithyroid drugs (propylthiouracil, methimazole) meet.
See p. 316 in First Aid 2014 for visual at bottom of page
