Endo: Thyroid And Parathyroid Glands

Front 1

Structure Thyroid and Parathyroid Glands

Back 1

Thyroid - large right and left lobes (each 20g) joint by narrow isthmus overlying 2nd tracheal cartilage. +/- pyramidal lobe extending from isthmus

Parathyroid glands - 2 pairs of tissue embedded in posterior surface of lateral lobes of thyroid gland - variable position, only a few mm diameter

Front 2

Development of Thyroid and Parathyroid

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Develops from endodermal lining of primitive pharynx around week 4 of gestation, grows caudally and forms ductlike infagination called thyroglossal duct

Migrates and leaves behind embryologic remnant (pyramidal lobe seen in 40%)

At week 9, endodermal cells become plates of follicular cells

Week 14, well developed follicles with colloid lumens

Week 7 epidermal cells lining 4th brachial pouches migrate to thyroid, disperse and give rise to parafollicular cells

Front 3

Histology of Thyroid gland, cells

Back 3

Thousands of follicles various size, CT arround with network of FENESTRATED capillaries and blind-ended lymphatic capillaries and nerve fibers

Cells:
a) Follicular cells - make up the epithelium of follicles, cells in contact with colloid
b) Parafollicular cells (C cells) - at periphery of follicles, lie in basal lamina but NOT in contact with colloid

Front 4

Blood supply to thyroids

Back 4

Fenestrate network of capillaries from superior and inferior thyroid arteries surround follicles and supply parathyroids

Hormones drain to thyroid veins and eventually jugular

Front 5

Follicle structure

Back 5

Cyst-like compartments formed by SIMPLE CUBOIDAL epithelium known as follicular epithelium

Contain gel-like mass called colloid, oriented with apical surfaces in contact with colloid and basal surface on a typical basal lamina

Colloid is storage site for T3 and T4 bound to thyroglobulin

Front 6

Thyroid Hormones produced

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Thyroxine (T4) and triiodothyronine (T3) which stimulate rate of metabolism, precursors of T3 and T4 will be stored in lumen of thyroid follicles until released

Calcitonin - decreases circulating calcium and stores it in bones

Front 7

Follicular Cells role, structure, histology

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Role: synthesis and secretion of T3 and T4

Structure: range from low cuboidal to low columnar epithelium (tallest when stimulated) with junctional complexes at apex

Histology: Round nucleus, MAY have 2 nucleoli, slightly basophilic cytoplasm. Apical lysosomes, mitochondria, supranuclear Golgi and short villi extending into colloid, MANY vesicles and colloidal resorption droplets. Enzymes for absorption and secretion

Front 8

Colloid and Thyroglobulin

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Colloid is mostly iodinated glycoprotein called thyroglobulin, synthesized in RER, modified and packaged in Golgi and transported to apical membrane

Thyroglobulin is NOT a hormone but scaffold for synthesis and storage of thyroid hormone

Storage of large amounts of secretory products extracellularly

Front 9

Regulators of thyroid hormone synthesis, biosynthesis steps

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Hormone synthesis regulated by iodine levels in follicular cells and by TSH stimulation

Iodide is actively transported into cell via Na/I symport (2ndary AT) at basal membrane (gradients powered by Na/K ATPase), iodide transported across apical membrane via iodide/chloride passive transport in pendrin enzyme. Iodide oxidized to iodine by thyroid peroxidase on extracellular membrane, enters colloid and thyroglobulin becomes iodinated at the colloid. Iodinated thyroglobulin results in MIT and DIT formation

Front 10

Release of thyroid hormone

Back 10

TSH released from anterior pituitary, binds TSH receptors at basal membrane follicular cells triggering T3 and T4 synthesis and secretion

Filopodia at apical membrane and endocytose colloid conents via megalin (thyroglobulin receptor)

Vesicles fuse with endosomes and thyroglobulin molecules cleaved into MIT and DIT and T3 and T4, iodine removed from MIT and DIT and products reused

T3 and T4 released at basal membrane into CT for bloodstream

Front 11

Balance of T3 and T4 secretion

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T4 is substantially more secreted than T3

HOWEVER 40% peripheral T4 converted to the more potent T3 hormone

Front 12

Physiologic Effect of TH

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bind hormone specific thyroxin-binding proteins or non-specific serum proteins and transported

In target cells, TH bound to intracellular proteins, bind nuclear thyroid hormone receptor, increases cellular metabolism. T3 has shorter half life

Front 13

General T3 and T4 functions
a) Basal Metabolism
b) Carb, lipid and protein metabolism
c) Heart
d) Nervous System
e) Musculoskeletal
f) Reproductive

Back 13

a) Basal Metabolism - increases rate, body temp, appetite
b) Carb, lipid and protein metabolism - glucose catabolism, lipolysis, more cholesterol excretion in bile, stimulates protein synthesis
c) Heart - promotes normal cardiac function, increased contractility
d) Nervous System - promotes normal neuron development, physiologic function, enhances SNS
e) Musculoskeletal - promotes body growth, skeletal maturation, development and function of muscle
f) Reproductive - female reproductive activity and lactation

Front 14

Parafollicular Cells Location, Histology, Role

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Location: individually or in clusters at periphery of follicles but not in lumen

Histology: Small dense calcitonin granules

Role: High calcium in blood (NOT HORMONES FROM PITUITARY) stimulates release of calcitonin

Calcitonin inhibits bone resorption (osteoclasts) and stimulates absorption of calcium in bones (osteoblasts). Decreases calcium concentration in blood

Front 15

Clinical Changes in Grave's Disease

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Hyperplasia of follicular cells 2-3x
Hormone production is increased 10x (T3 and T4)
Most common cause is autoimmune IgG binding to and stimulating follicular cells

Front 16

Clinical Changes in Hypothyroidism

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Low thyroid hormones in body
Fatigue, excessive sleeping, muscular and mental sluggishness, slow heart rate, decreased CO

Front 17

Clinical Changes in Simple goiter

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Enlargement/swelling of thyroid most commonly due to iodine def.

Front 18

Parathyroid Glands Location, Role, Histology, Cell Types

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On posterior surface of thyroid gland, produce PTH which acts to maintain optimal Ca++ concentrations in blood and interstitial flood

Absence is INCOMPATIBLE with life

Histology: Small glands weighting about 40mg, cells in cords or clusters surrounded by reticular fibers, blood vessels, lymphatics and nerves. CT in older adults may have many adipose cells occupying 60% of gland.

Cell Types:
Chief cells - major functional cells, contain dense granules of PTH that is released by exocytosis
Oxyphil cells - Larger than chief cells, do not appear to secrete hormone

Front 19

PTH Synthesis and Action, Regulation

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Chief cells - pro-parathormone, signal sequence is cleaved, ER transport, pro-PTH, travels to Golgi, pro sequence removed leaving mature PTH

Regulation: Serum calcium levels, no tropic hormone involved in secretion of PTH

Receptor - Binds both C terminal and N terminal PTH, receptor interacts with a Ga(s) system, Receptors in OSTEOBLASTS and epithelial cells of PCT

Front 20

Effects of PTH

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Maintain proper Ca++ and Phosphate levels
Calcium sensing receptors on chief cells detect low calcium serum in body, stimulate production and secretion of PTH, High calcium inhibits PTH secretion

PTH stimulates:
bone resorption, Ca++ release, Ca++ absorption from food by intestines, conservation of calcium by kidneys, conversion of 25-OH Vit D3 to active 1,25(OH)2 Vit D

Front 21

PTH/Osteoclast simulation

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PTH binds to receptors on osteoblasts and progenitor cells to increase RANK production and decreasing osteoprotegerin (OPG) secretion

Higher RANK expression at surface stimulates osteoclast differentiation and activtion, and therefore more bone resoprtion

Front 22

PTH and Calcitonin balance

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Both controlled by circulating levels of Ca++, increases in blood Ca++ = more calcitonin release, less PTH. Decrease does opposite

Calcitonin rapidly reduces plasma Ca++ levels, PTH works more slowly to ensure adequate calcium levels maintained

Front 23

Primary Hyperparathyroidism vs Hypothyroidism

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Hyperparathyroidism - may be caused by a tumor in one of the glands. Marked high blood calcium levels, low blood phosphate levels, loss of bone mineral and kidney stones

Hypothyroidism - from def in PTH. LOW blood calcium, retention of bone calcium and increased phosphate resorption in the kidneys. Numbness, tingling, muscle cramps, mental confusion and memory loss

Front 24

Pineal gland, location, role,

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Cone shaped projection from diencephalon roof, covered by pia mater, divided into incomplete lobules by CT septae and blood vessels

Has melatonin-secreting pinealocytes

Secretions influenced by light and dark periods of day, darkness stimulates melatonin production and light suppresses. Involved in both circadian and seasonal biorhythms

Can take melatonin for SAD, jet lag