Endo - Physiology (Thyroid & Parathyroid)

Question 1

What is the source of PTH?

Answer 1

Chief cells of parathyroid

Question 2

What 4 major functions does PTH have?

Answer 2

(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

Question 3

What effect does PTH have on serum and/or urine levels of Ca2+ and (PO4)3-?

Answer 3

PTH increases serum Ca2+, decreases serum (PO4)3-, and increases urine (PO4)3-

Question 4

Again, what function does PTH have with regard to bone? What is the mechanism behind this function?

Answer 4

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+

Question 5

What effect does PTH have on phosphate (PO4)3- levels in the serum and urine? What is a good way to remember this?

Answer 5

PTH decreases serum phosphate and increases urine phosphate; Think: “PTH = Phosphate Trashing Hormone”

Question 6

What are the 3 methods for regulation of PTH based on serum levels, and what effect(s) do they have on PTH secretion?

Answer 6

(1) Low serum Ca2+ –> Increased PTH secretion (2) Low serum Mg2+ –> Increased PTH secretion (3) Very low serum Mg2+ –> Decreased PTH secretion

Question 7

What is PTHrP? In what conditions is it commonly increased?

Answer 7

PTH-related peptide (PTHrP) functions like PTH & is commonly increased in malignancies (e.g., paraneoplastic syndromes)

Question 8

What effect do low and very low serum Mg2+ have on PTH secretion?

Answer 8

Low serum Mg2+ –> Increased PTH secretion; Very low serum Mg2+ –> Decreased PTH secretion;

Question 9

Again, what effects do low and very low serum Mg2+ have on PTH secretion? What are 4 common causes of low Mg2+?

Answer 9

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

Question 10

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.

Answer 10

See p. 314 in First Aid 2014 for visual at bottom left

Question 11

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.

Answer 11

See p. 314 in First Aid 2014 for visual at bottom right

Question 12

What are 2 types of negative feedback on PTH?

Answer 12

(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

Question 13

What are 3 forms in which plasma Ca2+ exists, and what percentage is each of these forms?

Answer 13

Plasma Ca2+ exists in 3 forms: (1) Ionized (~45%) (2) Bound to albumin (~40%) (3) Bound to anions (~15%)

Question 14

How does an increase in pH affect Ca2+? What is the source of clinical manifestations, and what are 4 examples of clinical manifestations?

Answer 14

Increase in pH => Increased affinity of albumin (negative charge) to bind Ca2+ => clinical manifestations of hypocalcemia (cramps, pain, paresthesias, carpopedal spasm)

Question 15

What is another name for Vitamin D?

Answer 15

Vitamin D (cholecalciferol)

Question 16

What are two sources of Vitamin D? To what forms are both converted, and where? Which form is active?

Answer 16

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

Question 17

What are 2 functions of Vitamin D?

Answer 17

(1) Increases absorption of dietary Ca2+ and (PO4)3- (2) Increases bone resorption –> increased Ca2+ and (PO4)3-

Question 18

What are 4 regulators of Vitamin D, and how does each accomplish their regulation?

Answer 18

(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

Question 19

What does Vitamin D (cholecalciferol) deficiency cause in kids versus adults?

Answer 19

Deficiency causes rickets in kids and osteomalacia in adults

Question 20

What are 4 causes of Vitamin D (cholecalciferol) deficiency?

Answer 20

Caused by (1) malabsorption (2) low sunlight (3) poor diet (4) chronic kidney failure

Question 21

Name an inactive form of vitamin D, besides 25-OH D2 or D3.

Answer 21

24,25-(OH2) D3 is an inactive form of vitamin D

Question 22

Explain the difference in effects of PTH versus 1,25-(OH)2 (vitamin D) in terms of Ca2+ and (PO4) 3- reabsorption/absorption.

Answer 22

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

Question 23

What is the source of calcitonin?

Answer 23

Parafollicular cells (C cells) of thyroid

Question 24

What is the function of calcitonin?

Answer 24

Decreased bone resportion of Ca2+; Think: “calciTONin TONes down Ca2+ levels”

Question 25

What regulates calcitonin?

Answer 25

Increased serum Ca2+ causes calcitonin secretion

Question 26

What role does calcitonin play in Ca2+ homeostasis?

Answer 26

Calcitonin opposes action of PTH. Not important in normal Ca2+ homeostasis.

Question 27

What are the thyroid hormones? What do they contain, and what (in general) do they control?

Answer 27

Thyroid hormones (T3/T4); Iodine-containing hormones that control the body’s metabolic rate

Question 28

What is the source of thyroid hormones (T3/T4)? Where is most T3 formed?

Answer 28

Folicles of thyroid. Most T3 formed in target tissues.

Question 29

What are the 5 major functions of thryoid hormones (T3/T4)?

Answer 29

(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”

Question 30

What is TBG, and what role does it play? How does this role effect hormone activity?

Answer 30

Thyroxine-binding globulin (TBG) binds most T3/T4 in blood; only free hormone is active

Question 31

What is a condition in which TBG is decreased? In what context/conditions is TBG increased?

Answer 31

Low TBG in hepatic failure; High TBG in pregnancy or OCP use (estrogen increases TBG)

Question 32

Of T3 and T4, which is the major thyroid product? How is the other derived, and where?

Answer 32

T4 is major thyroid product; converted to T3 in peripheral tissue by 5’-deiodinase

Question 33

Contrast T3 and T4 in terms of affinity.

Answer 33

T3 binds receptors with greater affinity than T4

Question 34

In terms of the thyroid, what roles do peroxidase play?

Answer 34

Peroxidase is enzyme responsible for oxidation and organification of iodide as well as coupling of monidotyrosine (MIT) and diiodotyriosine (DIT)

Question 35

What is the mechanism of Propylthiouracil versus Methimazole?

Answer 35

Propylthiouracil inhibits both peroxidase and 5’-deiodinase; Methimazole inhibits peroxidase only

Question 36

What are 3 methods of regulation on thyroid hormones?

Answer 36

(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)

Question 37

What is the Wolff-Chaikoff effect?

Answer 37

Wolff-Chaikoff effect - excess iodine temporarily inhibits thyroid peroxidase => low iodine organification => low T3/T4 production

Question 38

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.

Answer 38

See p. 316 in First Aid 2014 for visual at bottom of page