ENDO 3 Flashcards
1
Q
About 93 % of the active hormones
secreted by the thyroid gland is — while on 7 % is —
A
Thyroxine (T4)
Triiodothyronine (T3)
2
Q
is T3 or T4 more potent?
A
T3
3
Q
Thyroid hormones impact (2). They also
have permission action on
—
A
metabolism and growth/development
catecholamines
4
Q
Calcitonin
decreases
A
plasma
calcium
5
Q
— is Required for Thyroid
Hormone Synthesis so Thyroid Follicular
Cells Actively Transport —
obtained from the diet.
A
Iodine (I2)
Iodide (I-)
6
Q
Na+/I– symporter (NIS) is capable of producing intracellular I– concentrations that are --- times as great as the concentration in plasma.
A
20–40
7
Q
Iodide must also exit the thyrocyte across the apical membrane to access the colloid, where the initial steps of thyroid hormone synthesis occur. --- is a Cl –/I– exchanger.
A
Pendrin
8
Q
T3 and T4 Secretion into Blood (4 steps)
A
- Colloid is internalized by endocytosis.
- The vesicles fuse with lysosomes in the cell.
- Proteases cleave T3 and T4 from TG.
- T3 and T4 diffuse out of the cell and into
capillaries.
9
Q
Colloid is a reservoir
of
A
thyroid hormones. “Humans can ingest a diet completely devoid of iodide (I-)for up to 2 months before a decline in circulating thyroid hormone levels is seen"
10
Q
~99% of T3 and T4 bind with plasma proteins for transport: (3)
A
- Thyroxine-Binding Globulin (TBG), Transthyretin (TTR), Albumin
11
Q
Due to the strength of its binding to the transport protein, – has a long
half-life (6-7 days).
A
T4
12
Q
– doesn’t bind as tightly so its half-life is only 2-3 days.
A
T3
13
Q
Target cells make active T3 by using enzymes called — that remove an iodine from T4.
A
Deiodinases/Iodinases
14
Q
Individual target cells can alter their exposure to T3 by regulating their
A
tissue Deiodinase
synthesis.
15
Q
There are three different Deiodinases (D1, D2, D3). All contain the
rare amino acid —, with — in place of sulfur,
which is essential for their enzymatic activity.
A
selenocysteine
selenium (Se)
16
Q
SKIPPED:
Various conditions inhibit Deiodinase activity:
A
selenium deficiency,
burns, trauma, advanced cancer, cirrhosis, chronic kidney disease,
MI and febrile states, fasting, stress. Could show signs of
hypothyroidism.
17
Q
T3 actions occur sooner
(than T4) with the
maximum activity
A
~2-3
days.
18
Q
Negative feedback: mainly at the
level of
A
anterior pituitary gland
19
Q
– is the main circulating form;
responsible for most of the (-)
feedback
A
T4
20
Q
TSH secretion is
A
pulsatile (note the stars
below that show pulses). Output starts to rise
at about 9:00 PM, peaks at midnight, and then
declines during the day.
21
Q
Effects of Thyroid Hormone on Metabolism (5)
A
- Stimulates oxygen consumption by most metabolically active tissues.
- Increased Basal Metabolic Rate (BMR)
- Stimulates carbohydrate metabolism tract
- Stimulates protein catabolism & synthesis
- Stimulates fat metabolism
22
Q
Stimulates carbohydrate metabolism (3)
A
– Causes uptake of glucose by cells
– Enhances glycolysis & gluconeogenesis
– Increases rate of CHO absorption from G.I.
tract
23
Q
Stimulates fat metabolism (3)
A
– Increases lipid mobilization & oxidation of fatty acids by cells
– Required to convert beta carotene to vitamin A (Hypothyroid patients have yellowish skin)
– Decreases circulating cholesterol levels (Hypothyroidism associated with hyperlipidemia)
24
Q
Other Effects of Thyroid Hormones
NS: (5)
A
• Needed for normal development of the NS • Impacts reflex time (i.e. hypothyroidism can cause prolonged reflex times) • Muscle tremors due to increased reactivity of neuronal synapses • Feeling of tiredness but difficulty sleeping • Anxiety, worry and paranoia
25
Other Effects of Thyroid Hormones
| ES: (3)
```
• Increased glucose consumption
results in increased insulin
secretion being needed to
maintain blood glucose levels
• Activation of bone formation
causes a need for increased
PTH secretion
• Causes increased inactivation of
glucocorticoids which leads to
more ACTH release
```
26
```
Other Effects of Thyroid Hormones
Cardiovascular System (2)
```
• Increased expression of β-
adrenergic receptors
• Increased blood flow, heart
rate, and heart contractility.
27
Other Effects of Thyroid Hormones
| GI: (2)
```
• Increased appetite and food intake
• Increased rate of secretion and
motility of the GI tract (i.e.
hypothyroidism can produce
constipation)
```
28
Goiter is
an enlarged thyroid that does not indicate
| functional status.
29
Goiter is seen in (3)
Hypothyroidism, Hyperthyroidism, Euthyroidism
30
Goiter caused by excessive amounts of -- secretion.
TSH
31
High TSH stimulates thyroid to secrete large amounts of
| thyroglobulin colloid into follicles, resulting in
gland
| enlargement
32
---is the most common form
| of hyperthyroidism
Graves’ Disease
33
Hyperthyroidism can also occur due to a
thyroid
| adenoma.
34
Graves’ Disease
An autoimmune disease where antibodies
to TSH receptor called thyroid-
stimulating immunoglobulins (TSIs)
stimulate the thyroid gland to excess
35
TSI antibodies have prolonged stimulating
| effect on thyroid gland, lasting as much as
12 hours, in contrast to TSH of ~1 hour
36
```
High levels of thyroid hormone secretion
caused by (2)
```
```
TSI suppress anterior pituitary
TSH secretion (negative feedback)
```
37
Treatment of Hyperthyroidism (3)
```
• Radioactive I 131 thyroid
ablation, or Antithyroid Drugs
(propylthiouracil or
methimazole).
– Surgery rarely indicated.
• Propanolol (b blocker) given
for adrenergic symptoms while
awaiting resolution.
• L-thyroxine administered to
prevent hypothyroidism in
patients who have undergone
ablation or surgery
```
38
Hyperthyroidism Oral Symptoms (5)
* Burning Mouth Syndrome
* Gum disease
* Excessive salivation
* Weakening of mandible
* Increased caries risk
39
Burning Mouth Syndrome is more common in
women ?50
40
Thyroid Storm (Thyrotoxicosis)
Elevated Thyroid Hormone with stressful events (trauma, surgery,
severe emotional distress) or serious illness (DKA, MI, etc.).
41
```
Thyroid Storm (Thyrotoxicosis)
symptoms:
```
fever, tachycardia, elevated BP, nausea, vomiting,
| diarrhea, breathing problems, etc.
42
In patients with hyperthyroidism or those that exhibit
signs/symptoms of it, administration of -- is
contraindicated and elective dental care should be deferred.
epinephrine
43
Hashimoto’s Thyroiditis
• Autoimmune reaction against thyroid gland destroys
| gland rather than stimulating it.
44
Most common cause of hypothyroidism
Hashimoto’s Thyroiditis
45
Hashimoto’s Thyroiditis
| Most patients first exhibit autoimmune
"thyroiditis,”
| thyroid inflammation
46
Hashimoto’s Thyroiditis
| Inflammation leads to fibrosis of thyroid resulting in
decreased secretion of thyroid hormone.
47
Hypothyroidism due to low ---
iodine
48
In hypothyroid states:
Goiter: --- deficiency
No goiter: --- deficiency
iodine
| TSH
49
Myxedema
| • Seen in severely
hypothyroid patients
50
Myxedema
```
Increased quantities of
hyaluronic acid and
chondroitin sulfate bound
with protein plus water
accumulate in skin.
```
51
Other characteristics of
| hypothyroidism:
```
low BMR,
mental capacity, body
temp., appetite, HR, RR,
BP; anemia, weakness,
lethargy, wt. gain; increased
cholesterol and blood lipids
```
52
Myxedema tx
thyroxine (T4)
53
SKIPPED
| Early symptoms of myxedema are
```
fatigue, lethargy, cold intolerance,
constipation, stiffness and
cramping of muscles, carpal tunnel
syndrome, menorrhagia, slowing of
intellectual and motor activity,
decline in appetite, increase in
weight, and deepening of voice.
```
```
There is a dull, expressionless
facies, with puffiness of eyelids.
Skin appears swollen, cool, waxy,
dry, coarse, and pale with
increased skin creases.
```
54
Cretinism
• Thyroid hormones required for
| postnatal brain maturation.
55
Cretinism
| Results from: (2)
```
– Congenital absence of thyroid gland
(congenital cretinism)
– Iodine deficient diet (endemic
cretinism): most common cause
worldwide
```
56
Cretinism causes
physical and mental
| retardation of neonates
57
in Cretinism, skeletal growth is more inhibited than
soft tissue growth (obese,
stocky and short with large
protruding tongue)
58
Hypothyroidism Oral Manifestations (6)
• Macroglossia
• Dysgeusia
• Delayed tooth eruption
• Poor wound healing and increased risk of infection
(due to decreased activity of fibroblasts)
• Increased periodontal disease
• Salivary gland enlargement
59
Patients with hypothyroidism are sensitive to (2), so these medications should be
used sparingly
central nervous
| system depressants and barbiturates
60
phosphate storage
85%
14-15%
1%
85% bones,
14-15% in cells
less than 1% in the EC fluid (HPO42- and H2PO4-)
61
Changes in the phosphate level of the EC fluid to --X normal does not
cause major immediate effects.
2-3
62
Only 0.1% of total body --- is in the
EC fluid. 1% is in cells and organelles and the
rest is stored in bones. Free calcium is tightly
regulated (5%)
CALCIUM
63
Calcium:
– Too low =
– Too high =
– Too low = neuronal hyper-excitability (tetany)
| – Too high = neuronal depression
64
Control points for calcium and phosphate (3)
1. Absorption – via intestines
2. Excretion – via urine (calcium and phosphate) and feces (calcium only)
3. Temporary storage – via bones (hydroxyapatite) Ca10 (PO4)6 (OH)2
65
Parathyroid Hormone (PTH) (4)
• increase Plasma Calcium and decrease Phosphate
– Mobilizes calcium from bone
– Enhances renal reabsorption of calcium
– Increases intestinal absorption of calcium (indirectly)
66
Calcitriol (1,25-dihydroxycholecalciferol or vitamin D3) (2)
• increase Plasma Calcium and increase Phosphate
– Calcitriol is the primary hormone that enhances intestinal absorption of
calcium and it also causes absorption of phosphate.
67
Calcitonin (from the Parafollicular cells of the thyroid
| gland) (2)
• decrease Plasma Calcium and decrease Phosphate 21
Bone formation is stimulated by Calcitonin, Insulin, GH,
IGF-1, Estrogen and Testosterone
68
Vitamin D3 & Parathyroid Hormone
| Stimulate
Bone Matrix Resorption increase plasma calcium
69
Calcitonin Stimulates
Bone Matrix Deposition & Inhibits Osteoclasts
| decreases plasma calcium
70
--- affects almost 10 million individuals in the US, though only a small
proportion are diagnosed and treated. It occurs when there is an imbalance between
bone formation and resorption.
Osteoporosis
71
Osteoporosis risk factors
vitamin D deficiency (secondary hyperparathyroidism),
inadequate calcium intake (secondary hyperPTH),
glucocorticoid medications,
reduced physical activity,
estrogen deficiency (post-menopausal),
cigarette smoking, alcohol, etc.
72
Treatments for Osteoporosis (6)
```
• Exercise (walking and weight-
bearing 3X per week)
• Physical Therapy (postural
exercises, muscle strengthening)
• Estrogen (replacement or
receptor agonists)
• Calcium (carbonate or citrate)
• Vitamin D
• Bisphosphonates
```
73
Parathyroid Glands
Four pea-sized glands on the posterior
| surface of the thyroid gland.
74
```
Parathyroid Hormone (PTH)
• Secreted by the
```
Chief Cells
75
PTH:
• increase plasma calcium by (3)
• decrease plasma phosphate by (1)
(1) increase Intestinal Absorption,
(2) decrease Renal Excretion and
(3) increase Bone resorption.
(1) increase Renal Excretion
76
↓ ECF Ca2+ concentration
```
increase rate of PTH secretion
hypertrophy of
parathyroid gland
o Pregnancy
o Rickets
o Lactation
```
77
increase ECF Ca2+ concentration
↓ activity of parathyroid gland
↓ size of parathyroid gland
o increased vitamin D intake
o excess quantities of calcium in the diet
o bone resorption caused by factors other than PTH
78
Increases Plasma Calcium (3)
1. Bone Resorption
2. Reabsorption of Calcium
by Renal Tubules which
reduces excretion
3. Converts 25-
hydroxycholecalciferol to
1,25-
dihydroxycholecalciferol
(Vitamin D/Calcitriol),
which causes intestinal
calcium absorption.
79
Decrease Plasma Phosphate (1)
4. Decreased reabsorption
by renal tubules leading
to increased urinary
excretion
80
Calcitonin
```
Peptide hormone
secreted by
parafollicular cells
(C cells) of the
thyroid gland
```
81
Calcitonin is released in response to
elevated
| free plasma Ca2+
82
Calcitonin lowers
```
plasma Ca2+
by decreasing
activity of
osteoclasts, thus
decreasing bone
resorption
```
83
Calcitonin: not a major controller of -- in humans
calcium
84
Primary Hyperparathyroidism
Excess PTH secretion due
to a parathyroid gland
tumor
85
Extreme osteoclastic
activity in bones causes
cystic bone disease
(osteitis fibrosa cystica) (4)
```
– Hypercalcemia leads to
polyuria and calcuria
– Low phosphate due to
increased renal excretion
– Muscle weakness and
easy fatigability
– Osteoblastic activity also
increased leading to high
secretion of alkaline
phosphatase (ALP).
```
86
Secondary Hyperparathyroidism
• High PTH levels occur as compensation for hypocalcemia
| not due to primary abnormality of parathyroid glands
87
Causes of hypocalcemia: (2)
– Vitamin D deficiency
| – Chronic renal disease-cannot synthesize Vit D3
88
Vitamin D deficiency leads to --- in children,
--- in adults [inadequate mineralization of
bones] and high PTH, which causes bone resorption. High
PTH is a risk factor for osteoporosis and fractures.
rickets
| osteomalacia
89
Primary Hypoparathyroidism:
| Less common-often results from accidental
surgical
| parathyroid gland removal
90
Parathyroid gland removal decreases plasma Ca++
| levels from -- to --
10 mg/dL to 6-7 mg/dL
91
Hypocalcemia increases membrane Na+
| permeability leading to (3)
neuromuscular excitability &
| muscle spasms & tetany
92
Spasm of laryngeal muscles obstructs respiration
| causing --- unless appropriate treatment applied
death
