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BIOCHEMISTRY > ME04 - Thyroid/Parathyroid > Flashcards

ME04 - Thyroid/Parathyroid Flashcards

1
Q

One of the largest endocrine glands
Located below the larynx on each side of the trachea
Weighs 15 to 20g in adults

A

Thyroid Gland

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2
Q

Cells seen in Thyroid Gland:

A

Follicular Cells: secrete hormones, cuboidal _(inactive) to columnar (active) _

Parafollicular Cells: Scattered among _follicular cells and in spaces between the spherical follicles which secrete calcitonin _

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3
Q

Cells seen in Parathyroid Gland:

A

Chief Cells
_ Produce PTH _
_ Small, polygonal, darkly staining, abundant cells _
_ Contain lakes of glycogen giving them a water clear appearance

Oxyntic cells _
_ Function unknown _
_ Large, light staining, fewer in numbers _
_ Only present at age 6 onwards _

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4
Q

Differentiate T4 from T3

A

T4 (Thymin Tetraiodothyroxin)
More half life (6 days)
More affinity for binding plasma protein
Less Binding to nuclear receptor
Onset of action is 4x slower (2 days)

T3 (Thyronine Triiodothyronine) - ACTIVE
Less half life (1 day)
Less affinity for binding plasma protein
More Binding to nuclear receptor
Onset of action is 4x faster (12 hours)

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5
Q

Steps in the Synthesis of Thyroid Hormones

A

STEPS:
1. Iodide trapping
2. Formation and secretion of thyroglobulin
3. Oxidation of iodine
4. Organification of thyroglobulin
5. Storage and secretion

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6
Q

_ Basal membrane of the thyroid actively pumps iodide to the cell interior (Na-I symporter)
_ Concentrates the iodide to about 30 - 250 times its concentration in the blood

A

Iodide Trapping

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7
Q

What stimulates Iodide Trapping

A

TSH

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8
Q

What are involved in the Formation of Thyroglobulin

A

Thyroid cell endoplasmic reticulum and Golgi apparatus synthesize the glycoprotein thyroglobulin and secrete to the follicle colloid

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9
Q

Oxidation of Iodine

A

_ Conversion of iodide to nascent iodine I0 or I3
_ Promoted by peroxidase and its accompanying hydrogen
peroxide
_ Peroxidase is located in the apical membrane of the cell
or attached to it, so the iodine will be readily available
_ When peroxidase is blocked or hereditarily absent, the
rate of synthesis of thyroid hormone falls to zero

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10
Q

Binding of iodine to thyroglobulin

A

Organification of Thyroglobulin

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11
Q

Oxidized iodine is associated with what enzyme, which
speeds up the binding

A

Iodinase - speeds up the binding
_ Iodine binds with about 1/6 of the tyrosine molecules in
thyroglobulin

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12
Q

Final Formation of Thyroxine (T4) and Triiodothyronine (T3):

A

_ successive stages of iodination of tyrosine
_ COUPLING of iodotyrosine molecules
_ may occur in a matter of minutes or even days

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13
Q

Release of Hormones from Thyroid Gland

A

Apical surface of the cell sends out pseudopods to form pinocytic vesicles that engulf some colloid
Lysozymes fuse with the vesicles which have proteases that digest thyroglobulin
T4 and T3 will be in free form then diffuse to basal membrane into surrounding capillaries
T4 and T3 now enter circulation

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14
Q

Fate of Thyroglobulin

A

_ About 3_4 of iodinated tyrosine will not become T3 or T4 and remain only as mono- or diiodotyrosine that are cleaved from thyroglobulin as well
_ Iodine is cleaved from these through the deiodinase enzyme, which makes all the iodine available again for hormone synthesis
_ Congenital absence of deiodinase enzyme causes iodine deficiency due to failure of recycling

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15
Q

Daily Secretion of T4 and T3

A

93% of hormone released from thyroid is T4, only 7% is T3
During ensuing days, T4 is slowly deiodinated to T3 which is more readily available in the tissues
Delivery is about 35 micrograms of T3 per day

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16
Q

Transport of T4 and T3 to Tissues

A

Upon entering the blood, 99% of T4 and T3 bind to transport proteins secreted by the liver:
_ Main: Thyroxine-binding globulin
_ Less: Thyroxine-binding prealbumin and albumin
_ Half of T4 is released to tissues in 6 days
Half of T3 is released to tissues in 1 day (due to lower affinity to binding proteins)
Upon entering tissues, T4 and T3 bind with intracellular proteins (T4 T3 binding)
Hormones are stored and used slowly in the next few days or weeks

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17
Q

What is unique in Thyroid Hormone

A

Unique: can produce and store hormones for up to 3 months

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18
Q

Thyroid Hormone forms in plasma:

A

FORMS IN PLASMA
_ Thyroxine Binding Globulin :70%
_ Transthyretin or Thyroxine Binding
Prealbumin : 20%
_ Thyroxine Binding Albumin: 10%
_ Free Thyroxine : 0.03%

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19
Q

DECREASE in TBG results to:

A

Liver & kidney disease

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20
Q

INCREASE in TBG results to:

A

Estrogen or pregnancy

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21
Q

What happens after injection of thyroxine to the blood

A

The basal metabolic rate only increases after 2 to 3 days
Once activity begins, it lasts for 10-12 days then decreases with a half-life of 15 days

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22
Q

Triiodothyronine has a latency of ___________

A

6-12 hours

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23
Q

Maximal cellular activity of Thyroid Hormone

A

2-3 days

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24
Q

Rationale behind the latency of Thyroid Hormones

A

Latency is due to binding to protein and their slow
release and from how these are used in the cell

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25
Q

Where are Thyroid hormone receptors located?

A

In the DNA, they are nuclear receptors

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26
Q

Thyroid Hormones Activate Nuclear Receptors

A

Forms a heterodimer with retinoid X receptor (RXR) on
DNA
On binding with thyroid hormones, they initiate
transcription and eventual translation into intracellular
proteins
Whole process takes about minutes to hours (explains
latency)

27
Q

IMPORTANT ACTIONS OF THYROID HORMONES

A

_ Increases O2 consumption and Basal Metabolic Rate (BMR)
_ Increases mitochondria and Na-K-ATPase pump activity
_ Stimulates carbohydrate, fat and protein metabolism
_ Increases glucose uptake, gluconeogenesis,
glycogenolysis
_ Decreases cholesterol, phospholipids and
triglycerides but increases fatty acids
_ Increases cholesterol secretion to bile and
number of liver LDL receptors
_ Increase protein synthesis
_ Needed for Growth
_ Increases requirements for vitamins
_ Increases blood flow, Cardiac Output, Heart Rate, Heart
Strength
_ Increases respiration
_ Increases gastrointestinal motility
_ Increases cerebration
_ Increases muscle vigor
_ Fine Muscle Tremors
_ Increases risk for somnolence
_ Needed for proper sexual function
_ Loss may cause loss of libido, impotence, menstrual changes

28
Q

Example how TRH and TSH levels are mediated

A

_ Cold stimulates TRH secretion&raquo_space; Increased TSH&raquo_space; Increased T4, T3
_ Excitement, Anxiety&raquo_space; Increased TSH

29
Q

What are the effects of TSH

A

Proteolysis of thyroglobulin
Activity of Iodide Pump
Iodination of Tyrosine
Size & Secretory activity of thyroid cells
No of Thyroid cells

30
Q

Typically occurs with comparatively small increases in iodine intake, in people who have thyroid abnormalities that cause the gland to function without the control of the pituitary

A

Jod-Basedow Effect
Hyperthyroidism following administration of iodine or iodide, either as a dietary supplement or as contrast medium gland to function without the control of the pituitary.
_ Does not occur in persons with normal thyroid glands, as thyroid hormone synthesis and release in normal persons is controlled by pituitary TSH secretion, which does not allow hyperthyroidism when extra iodine is ingested

31
Q

Autoregulatory phenomenon that inhibits organification in the thyroid gland (inhibition of peroxidase), the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream.

A

Wolff-Chaikoff Effect
_ Reduction in thyroid hormone levels caused by ingestion of a large amount of iodine

_ Lasts several days (around 10 days), after which it is followed by an “escape phenomenon_o

32
Q

Resumption of normal organification of iodine and normal thyroid peroxidase function

A

Escape phenomenon

_ Due to decreased inorganic iodine concentration
secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell

33
Q

Differentiate Hyperthyroidism and Hypothyroidism

A

HYPERTHYROIDISM
Increased metabolic rate
Excitability, restlessness
INC appetite but with weight loss, protein wasting and muscle weakness (thyrotoxic myopathy)
Pre-tibial Myxedema (in 20% of patients)
Tachycardia, Increased cardiac output
Fine Tremors
Diarrhea

HYPOTHYROIDISM
DEC metabolic rate
Slow thought process, poor memory
Elevated plasma cholesterol and other lipids (atherosclerosis)
Fatigue, increased somnolence, Weight gain
WHOLE BODY MYXEDEMA
Prolonged relaxation phase of Deep Tendon Reflex (DTRs)
Hoarse voice
Constipation

34
Q

Autoimmune disease, anti-TSH receptor antibodies

A

Graves Disease

35
Q

Classic Triad of Grave_s Disease:

A

_ Exophthalmos
_ Goiter
_ Pre-Tibial Myxedema

36
Q

Most common cause of hyperthyroidism in those >50 y.o.`

A

Toxic Multinodular Goiter
_ Plummer_s Disease

37
Q

_ Results from congenital lack of thyroid gland, genetic defect of the thyroid gland or lack of iodine in the diet
_ Skeletal growth

A

Cretinism

38
Q

Characteristics of a person with Cretinism

A

Obese, stocky, short, large tongue

39
Q

MCC: Iodine deficiency

A

Primary Hypothyroidism

40
Q

_ Auto-immune disease presenting with increased lymphocytes and macrophages destroying the thyroid
_ Anti-Thyroglobulin, Anti-Microsomal antibodies

A

Hashimoto_s Thyroiditis

41
Q

TRH, TSH, T4 on Hyperthyroidism

A

1 Hyper 2Hyper 3Hyper
TRH Dec Dec Inc
TSH Dec Inc Inc
T4 Inc Inc Inc

42
Q

TRH, TSH, T4 on Hyporthyroidism

A

1 Hypo 2Hypo 3 Hypo
TRH Inc Inc Dec
TSH Inc Dec Dec
T4 Dec Dec Dec

43
Q

Composition of Bone

A

__ORGANIC MATRIX
_ Ground Substances (ECF + Chondroitin Sulfate + Hyaluronic Acid) Gelatinous medium _
_ Collagen Fibers _ (95% of Organic Matrix ) for TENSILE STRENGTH

__BONE SALTS _
_ Ca10(PO4)6(OH)2 _ - for COMPRESSIONAL STRENGTH _

44
Q

BODY CALCIUM Composition in the Bone

A

_ 99% as hydroxyapatite in Bone
_ 0.1% in the interstitium
_

45
Q

Free and ionized calcium is biologically active. True or False?

A

True, and this affects neurons (normal=2.4mmol/L)

46
Q

Calcium Metabolism on Positive and Negative Calcium Balance

A

__Positive calcium balance__ Calcium Intake > Calcium Excretion

__Negative calcium balance__ Calcium Intake

47
Q

Effect of PTH in Intestine

A

Indirectly INCREASES calcium and phosphate absorption by increasing Vitamin D metabolites

48
Q

Effect of Active Vitamin D Metabolites in Intestine

A

Increased Calcium and Phosphate Absorption

49
Q

Effect of PTH in Kidney

A

Decreased Calcium Excretion, Increased Phosphate Excretion

50
Q

Effect of Active Vitamin D Metabolites in Kidney

A

Increased Resorption of Ca and Phosphate but usually net increase in urinary calcium due to effects in GI tract and bone

51
Q

Effect of PTH on Bone

A

Calcium and Phosphate Resorption Increased by Continuous High Concentrations.
Low intermittent doses increase bone formation

52
Q

Effect of Active Vitamin D Metabolites on Bone

A

Direct effect is increased calcium and phosphate resorption;
Indirect effect is promoting mineralization by increasing the availability of Ca and Phosphate

53
Q

Effect of PTH on Net effect on serum levels

A

Serum calcium increased,
Serum Phosphate both decreased.

54
Q

Effect of Active Vitamin D Metabolites on Net effect on serum levels

A

Serum calcium and Phosphate both increased.

55
Q

Flow of Vitamin D Synthesis

A

Vitamin D comes from Cholesterol Starts at the Skin
Calciol (Cholecalciferol)
1st activation: Liver
Calcidiol (25 hydroxyCholecalciferol)
2nd activation: Kidney
Calcitriol (1,25 dihydroxyCholecalciferol)

56
Q

Secreted by the Parafollicular cells of the Thyroid

A

Calcitonin

57
Q

Function of Calcitonin

A

Decreases plasma calcium concentration
_ Decreases number and activity of osteoclast
_ Effects in Children > Adults

58
Q

Effects of Calcium on Parathyroid Hormone Secretion:

A

_ Magnesium effect on PTH is similar to calcium
o Hypomagnesemia stimulates PTH secretion
_ Increased phosphate forms calcium phosphate which reduces stimulation of Ca-sensitive receptors which trigger an increase in PTH

59
Q

End results of Hyperparathyroidism

A

_ Hypercalcemia
_ Hypophosphatemia

60
Q

Hyperparathyroidism due to great osteoclastic activity

A

Osteitis Fibrosa Cystica

61
Q

Osteoblast increases what enzyme in an attempt to neutralize osteoclast activity in Hyperthyroidism

A

Increases Alkaline Phosphatase

62
Q

Types of Hyperparathyroidism

A

1 _ Autonomous Secretion (Parathyroid adenoma)
2 _ Response to Normal Regulatory Stimuli (Nutrional, Renal)
3 _ Refractory Secondary | Nonsuppressible secretion after correction of metabolic abnormalities
4 _ Refractory Secondary with Hypercalcemia

63
Q

Hypocalcemia on Hypoparathyroidism

A

Hypocalcemia: interferes with normal muscle contraction and nerve conduction
_ Paresthesias
_ Tetany and Seizures
_ Possible laryngeal spasm
_ Fatigue, headaches, bone pain and insomnia, crampy
abdominal pain
_ Chvostek_s sign

BIOCHEMISTRY (25 decks)

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