Lecture #2 -- Thyroid Physiology Flashcards Preview

Physio -- Endocrine > Lecture #2 -- Thyroid Physiology > Flashcards

Flashcards in Lecture #2 -- Thyroid Physiology Deck (120):
1

What nerve should be watched out for in thyroid surgery

Recurrent Laryngeal Nerve

2

Where are thyroid hormone receptors located?

Intracellularly

3

Give an example of an endocrine, neurocrine, paracrine, and autocrine hormone.

Endocrine -- Insulin
Neurocrine -- ADH
Paracrine -- Gastrin
Autocrine -- Norepinephrine

4

Thyrotropin Releasing Hormone can stimulate the release of

Thyroid Hormones
Prolactin

5

How is thyroid hormone release regulated?

Negative Feedback from T3, T4 inhibits TSH release from the A Pit

6

Four structural groups of hormones

Peptides/Proteins
AA Derivatives
Steroids
Fatty Acid Derivatives -- Eicosanoids

7

Amine hormones are usually derived from

Tyrosine or Tryptophan

8

Six examples of Amine hormones

Triiodothyronine (T3)
Thyroxine (T4)
Dopamine
Epinephrine
Norepinephrine
Serotinin

9

Two other (non-tyrosine) AAs used in hormone synthesis?

Tryptophan -- Serotonin, Pineal Hormone Melatonin
Glutamic Acid -- Histamine

10

Peptide hormones are typically produced as....

Larger MW precursors that are proteolytically cleaved to active form

11

Peptide hormones are _______ soluble

Water

12

Is Thyrotropin (TSH) a peptide or steroid hormone?

Peptide

13

Is Vitamin D3 a peptide or steroid hormone?

Steroid

14

List Five types of steroid hormones

Glucocorticoids
Mineralocorticoids
Androgens
Estrogens
Progestogens

15

Major glucocorticoid in mammals?

Cortisol

16

Major mineralocorticoid in humans?

Aldosterone

17

Common Androgen and Estrogens?

Testosterone
Estradiol, Estrone

18

Most commonly considered progestogen?

Progesterone

19

What is the rate limiting step of steroid hormone synthesis?

Transport of free cholesterol from cytoplasm into mitochondria.

Carried out by Steroidogenic Acute Regulatory Protein

20

Describe the Adenylyl Cyclase pathway

Activated Receptor
Galpha--ATP release
Stims Ad Cyclase -- ATP --> cAMP
cAMP activates PKA and is turned to 5' AMP
Phosphorylation of Proteins
Physiologic Action

21

Describe the Phospholipase C pathway

Activated Receptor
Galpha--ATP release
Stims Phospho C --- PIP2 --> DAG+IP3
IP3 --> Calcium release from ER/SR
DAG + Ca --> PKC activity
PKC ---> Physiologic Actions

22

Example of receptor tyrosine kinases and tyrosine kinase - associated receptors

RTK -- NGF Receptor, Insulin
TK-Associated -- Growth Hormone

23

Describe the activation pathway of a steroid hormone

Hor thru membrane
Binds to intracellular receptor
Dimerization and binding to Sequence Response Element
Transcription.......Protein--> Physiologic Action

24

Amine (Epinephrine) -- Class and Receptor Location

Water Soluble
Cell Surface

25

Amine (Thyroid Hormone) -- Class and Receptor Location

Lipid Soluble
Intracellular

26

Peptide -- Class and Receptor Location

Water Soluble
Cell Surface

27

Steroids/Vitamin D -- Class and Receptor Location

Lipid Soluble
Intracellular

28

Primary function of thyroid?

Maintenance of all metabolic pathways needed for growth, development, body maintenance, and repair

29

As TRH release is constant, why aren't women constantly lactating?

Dopamine inhibition of prolactin

30

Where does TSH come from?

Basophil cells of the anterior pituitary

31

How does TSH stimulate thyroid hormone production

Iodide Uptake and Incorporation into Thyroglobulin
Release of T3 and T4 from thyroglobulin
Stimulates production of Cuboidal Cells of thyroid cells

32

Roles of Thyroid Hormones in Development

- Development of CNS in fetus/neonate
Stim differentiation, dendrite formation, and myelination
- Stim production/maint. of enzymes responsible for
synthetic/degrative pathways in metabolism
- Increase intermediary metabolism and ox phos
- Stim tissue growth and bone development
- Increase GH gene expression

33

Effect of thyroid hormone on metabolism (overall)

Stimulates the formation of the intermediate pathways of carbohydrates, fat, and protein metabolism

Amplifies cell metabolic activity and heat production

34

How does Thyroid Hormone mediate increased metab?

Stimulates mito. proteins, Na/K ATPase
Stim Anabolic Protein Pathways, Lipolysis, and lipogenesis
Produce positive chronotropic and inotropic effects on the heart

35

Functional unit of the thyroid gland =

Follicle

36

Thyroid embryology information

-Descends from foramen cecum as bilobed diverticulum in
front of pharynx
- Eventually resides over larynx with 2 lobes+isthmus
- Neural Crest gives C cells that fuse and disperse thruout

37

Connection that may exist between thyroid and tongue?

Thyroglossal Duct

38

What is the foramen cecum

Endodermal proliferative center at root of tongue

39

C cells are also known as...

Parafollicular Cells

40

Where are C cells from?

Ultimobranchial body (last structure derived from branchial pouches)

BIG PICTURE -- NEURAL CREST ORIGIN

41

What do C cells secrete?

Calcitonin

42

C cells are escalated in what disease state mentioned in class?

Medullary Thyroid Cancer
Can also be a side effect of meds

43

What is a pyramidal lobe?

Persistence of the Inferior Thyroglossal Duct
Attached to hyoid bone or incorpoated into a thyroglossal duct cyst

44

Clinical significance of thyroglossal duct cyst

Can form a sinus

Treat with "Sistrunk" Procedure (resect w/ part of hyoid)

45

Where should you look for an ectopic thyroid?

Can occur anywhere along the path of descent
Usually at the base of the tongue (lingual thyroid)

46

Molecularly, what are thyroid hormones

Double tyrosines with incorporation of 3 or 4 iodines

47

What do T3/T4 use for transport in the blood?

Thyroxine binding globulin

48

Who makes thyroglobulin?

Synth from tyrosine in the follicular cells
Then put in vesicles to the follicular lumen

49

Role of the Sodium-Iodide transporter

Actively transports I- into thyroid follicular cells for incorportation into thyroid hormones

50

What inhibits the Sodium-Iodide transporter?

Thiocyanate and Perchlorate Anions

51

What enzyme oxidized I to I2. Where?

Peroxidase Enzyme
Follicular Cell Membrane

52

What happens in organification?

I2 is combined with tyrosine on thyroglobulin
Forms MIT and DIT

53

Inhibitor of Peroxidase enzyme?

PTU

54

What is Wolff-Chaikoff?

High levels of I- inhibit organification which inhibits synthesis of Thyroid Hormone

55

DIT+DIT =

T4

56

DIT+MIT=

T3

57

What happens in the thyroid follicle following TSH stimulation?

Iodinated thyroglubulin is taken back into follicular cells by endocytosis

58

Describe the peripheral conversion of T4.
Why convert?

Converted to T3 by 5-iodinase
T3 is 3-4x as potent as T4

59

Decribe what happens after reuptake in the secretion fo T3/T4

Internalized vesicle joins with lysosome
Enzymes cleave T3/T4 from thyroglobulin
Some T4 is converted to T3
Released into extracellular space by diffusion

60

What happens to MIT/DIT attached to thyroglobulin after lysosome release into intracellular

Deiodinase converts them back to I-, recycled in the system

61

Say it all -- the steps of Thyroid Hormone Synth.

1. Thyroglobulin is synthesized in RER and Golgi
Sent to Lumen
2. Na-I cotransport
3. Oxidation
4. I2 combines with tyrosine moities
5. Coupling Rxns --> Make Colloid
6. Endocytosis upon stimulation
7. Hydrolysis of T3/4 from thy.glob. by lysosomal enzymes
8. Recycle MIT and DIT

62

What is rT3?
When might you expect to see it elevated in a patient?

Inactive form of T3
More shows up in patients that are especially sick
(Helps chill out metabolism)

63

Where does most conversation of T4->T3 take place?

Liver and Kidneys

64

How much thyroid hormone is bound?

Approx. 99.98%

65

What proteins bind thyroid hormone in the blood?

Thyroid Binding Globulin (75%)
Thyroid Binding Pre-Albumin (15-20%)
Albumin (5-10%)

66

Very small changes in free T4 will...

Alter TSH levels

67

Where do people get iodine from?

Dietary intake

68

Enzyme that inhibits Iodine oxidization?

PTU

69

Regulation of Iodinde uptake?

Negative Feedback
High Iodide levels --> Decreased Iodide uptake into Fol
Low Iodide --> Increased Uptake into Follicular

70

How is the Wolff-Chaikoff effect countered?

Iodide leak from the normal thyroid tissue

71

What may happen to patients with autoimmune thyroiditis?

Failure to adapt
Become hypothyroid

72

Jod-Basedow effect and Wolff-Chaikoff effect have what relationship?

They're opposites.

73

What does the Jod-Basedow Effect specify

Excessive Iodine Loads --> Hyperthyroidism
Seen in Graves, Toxic multinodular goiter, toxic adenoma

74

Jod-Basedow can lead to thyrotoxicosis if the excess iodine comes from...

Diet
Contrast Administration
Iodine containing meds

75

What happens with thyroid-binding globulin in pregnancy?

Increases occur secondary to estrogenic stimulation of TBG synthesis and reduce hepatic clearance

76

What causes the reduced hepatic clearance of thyroid-binding globulin in pregnancy?

Sialylation

77

hCG has what effect on thyrotropic activity

Increases it by directly activating TSH receptor

78

Timeline for hCG release

Begins shortly after conception
Peaks around gestational week 10
Declines to a nadir by approx. week 20

79

What happens in the TSH decline after the hCG increased it

Partial inhibition of Pit gland by cross reactivity of alpha subs
Can drop women's TSH levels to less than normal levels

80

How do thyroid hormones increase the basal metabolic rate?

Increasing Na-K ATPase and beta-1 adrenergic receptors

81

Describe the effect of thyroid hormone on protein synth/deg

Low Thyroid Hor --> Increased Protein Synth
High Thyroid Hor --> Increased Protein Degradation

82

Effects of thyroid hormone on the respiratory system?

Increase respiratory rate
Increase minute ventilation
Increase ventilatory response to hypercapnia/hypoxia

83

Effects of thyroid hormones on the renal system

Increased Blood Flow
Increased GFR

84

Effects of thyroid hormone on Oxygen-Carrying Capacity

Inc. RBC Mass
Increased O2 dissociation from hemoglobin

85

Effects of thyroid hormones on intermediary metabolism

Increased glucose absorption
Increase carbohydrate, lipid, protein turnover
Downregulate insulin receptors
Increase substrate availability

86

Effects of thyroid hormones in growth and tissue development

-Increase growth/maturation of bone, tooth, epidermis, hair follicles, nails
-Increased Rate/Force of Skeletal muscle contraction
-Inhibits synthesis/Inc. degrad of mucopolysaccharides

87

Effects of thyroid hormones on Nervous system

- Critical for development
- Wakefulness and Alertness
- Memory and Learning
- Normal Emotional Tone
- Speed and Amplitude of Periph. Nerve Reflexes

88

Effects of Thyroid on Reproductive System

- Req. for follicular development and ovulation
- Req. for pregnancy maintenence
- Req. for spermatogenesis

89

Effects of Glucocorticoids on Thyroid?

Excess --> decreased TSH
Diminished --> Increased TSH

90

Effect of estrogens on Thyroid activity?

Increase TBG, TSH
Increased T4 requirement

91

Effects of hypothyroidism in children?

Diminished Growth
Mental Retardation

92

Effects of hypothyroidism in adults?

Diminished metabolism
Cold Intolrance
Impaired mentation, Diminished nerve velocity
Loss of Appetite
Goiter

93

Five primary causes of hypothyroidism?

Iodine Deficiency
Hashimoto's (Autoantibody destruction of thyroid)
Hypothalamic/Pit Disease (low TRH/TSH)
Surgical Thyroid Removal
TH biosynthesis diseases

94

Relationship of hypothyroidism and goiter?

Diminished Thyroid Hormone --> Increased TSH
Increased thyroid bloodflow, stimulated FC
Increased in Colloid Production

95

Difference between primary and secondary hypothyroidism?

Primary -- Thyroid can't produce enough hormones
Secondary -- thyroid isn't being stimulated by pit to produce hors

96

Make a diagnosis...
Normal Free T4
Normal TSH

They're Fine

97

Make a diagnosis...
Low Free T4
High TSH

Primary Hypothyroidism

98

Make a diagnosis...
Normal Free T4
High TSH

Subclinical Hypothyroidism

99

Make a diagnosis...
Low Free T4
Normal or Low TSH

Secondary Hypothyroidism
TSH or TRH Deficiency

100

What is Hashimoto's thyroiditis?
Genetic Association?

Autoimmune destruction of the thyroid gland
Associated with HLA DR5

101

How do you treat hypothyroidism?

Levothyroxine (Synthetic T4)

102

What is Grave's Disease?

IgG locks activation of adenyl cyclase. Causes excess thyroid hormone production, assocaited with diffuse toxic goiter

103

Symptoms of Grave's Disease?

Nervousness, Irritability, Fatigue, Heat Intolerance, Cutaneous vasodilation, sweating, Inc. HR, Weight Loss

104

Common metabolic symptoms of hyperthyroidism

Low choleserol
High sugar from increased gluconeogenesis
Bone resorption
Decreased muscle mass

105

Who usually gets Grave's Disease?

Women 20-40

106

How does hyperthyroidism lead to Exopthalamos and dermopathy?

Fibroblasts in orbit and overlying shin express TSH
Activation --> Glycosaminoglycan buildup, Inflam., Fibrosis,
Edema

107

Influence of Thyroid hormones on sympathetic system?

Inc. synthesis of beta-1 receptors
(Inc. HR, pulse pressure, CO)

108

What EKG should you look out for in hyperthyroid patients?

Atrial Fibrilation

109

How is hyperthyroidism treated?

Beta-blockers
Surgery
Radioactive Iodine
PTU/Methimazole

110

Effects of PTU?

1. Blocks Peroxidase mediated oxidation, organification, and coupling
2. Blocks peripheral conversion of T4 to T3

111

Four Drugs that Block iodine uptake

Pertechnetate
Perchlorate
Thiocyanate
Nitrate

112

Effect of lithium on thyroid activity?

Inhibits iodination of thyroglobulin

113

Five classifications of thyroiditis?

Acute (Suppurative) thyroiditis
Subacute (granulomatous) thyroiditis
Silent (Painless) thyroiditis
Chronic lymphocytic (Hashimoto's) thyroiditis
Fibrous (Reidel's) thyroiditis

114

What tends to cause acute thyroiditis?

bacterial infection

115

What tends to cause silent thyroiditis?

Virus, Post-Partum

116

Most common thyroiditis?

Hashimoto's

117

Subacute thyroiditis key differential?

It really hurts

118

Three examples of subacute thyroiditis

Giant Cell Thyroiditis
Granulomatous thyroiditis
DeQuervain's Thyroiditis

119

Cause of Dequervain's thyroiditis?

Follows Viral Illness

120

How might you diagnose Reidel's fibrosing thyroiditis?

Extensive fibrosis formation
Hard as wood thyroid
Fibrosis may go to local structures, including airway