ENDO 3 Flashcards
About 93 % of the active hormones
secreted by the thyroid gland is — while on 7 % is —
Thyroxine (T4)
Triiodothyronine (T3)
is T3 or T4 more potent?
T3
Thyroid hormones impact (2). They also
have permission action on
—
metabolism and growth/development
catecholamines
Calcitonin
decreases
plasma
calcium
— is Required for Thyroid
Hormone Synthesis so Thyroid Follicular
Cells Actively Transport —
obtained from the diet.
Iodine (I2)
Iodide (I-)
Na+/I– symporter (NIS) is capable of producing intracellular I– concentrations that are --- times as great as the concentration in plasma.
20–40
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.
Pendrin
T3 and T4 Secretion into Blood (4 steps)
- 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.
Colloid is a reservoir
of
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"
~99% of T3 and T4 bind with plasma proteins for transport: (3)
- Thyroxine-Binding Globulin (TBG), Transthyretin (TTR), Albumin
Due to the strength of its binding to the transport protein, – has a long
half-life (6-7 days).
T4
– doesn’t bind as tightly so its half-life is only 2-3 days.
T3
Target cells make active T3 by using enzymes called — that remove an iodine from T4.
Deiodinases/Iodinases
Individual target cells can alter their exposure to T3 by regulating their
tissue Deiodinase
synthesis.
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.
selenocysteine
selenium (Se)
SKIPPED:
Various conditions inhibit Deiodinase activity:
selenium deficiency,
burns, trauma, advanced cancer, cirrhosis, chronic kidney disease,
MI and febrile states, fasting, stress. Could show signs of
hypothyroidism.
T3 actions occur sooner
(than T4) with the
maximum activity
~2-3
days.
Negative feedback: mainly at the
level of
anterior pituitary gland
– is the main circulating form;
responsible for most of the (-)
feedback
T4
TSH secretion is
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.
Effects of Thyroid Hormone on Metabolism (5)
- Stimulates oxygen consumption by most metabolically active tissues.
- Increased Basal Metabolic Rate (BMR)
- Stimulates carbohydrate metabolism tract
- Stimulates protein catabolism & synthesis
- Stimulates fat metabolism
Stimulates carbohydrate metabolism (3)
– Causes uptake of glucose by cells
– Enhances glycolysis & gluconeogenesis
– Increases rate of CHO absorption from G.I.
tract
Stimulates fat metabolism (3)
– 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)
Other Effects of Thyroid Hormones
NS: (5)
• 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
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
Other Effects of Thyroid Hormones Cardiovascular System (2)
• Increased expression of β-
adrenergic receptors
• Increased blood flow, heart
rate, and heart contractility.
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)
Goiter is
an enlarged thyroid that does not indicate
functional status.
Goiter is seen in (3)
Hypothyroidism, Hyperthyroidism, Euthyroidism
Goiter caused by excessive amounts of – secretion.
TSH
High TSH stimulates thyroid to secrete large amounts of
thyroglobulin colloid into follicles, resulting in
gland
enlargement
—is the most common form
of hyperthyroidism
Graves’ Disease
Hyperthyroidism can also occur due to a
thyroid
adenoma.
Graves’ Disease
An autoimmune disease where antibodies
to TSH receptor called thyroid-
stimulating immunoglobulins (TSIs)
stimulate the thyroid gland to excess
TSI antibodies have prolonged stimulating
effect on thyroid gland, lasting as much as
12 hours, in contrast to TSH of ~1 hour
High levels of thyroid hormone secretion caused by (2)
TSI suppress anterior pituitary TSH secretion (negative feedback)
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
Hyperthyroidism Oral Symptoms (5)
- Burning Mouth Syndrome
- Gum disease
- Excessive salivation
- Weakening of mandible
- Increased caries risk
Burning Mouth Syndrome is more common in
women ?50
Thyroid Storm (Thyrotoxicosis)
Elevated Thyroid Hormone with stressful events (trauma, surgery,
severe emotional distress) or serious illness (DKA, MI, etc.).
Thyroid Storm (Thyrotoxicosis) symptoms:
fever, tachycardia, elevated BP, nausea, vomiting,
diarrhea, breathing problems, etc.
In patients with hyperthyroidism or those that exhibit
signs/symptoms of it, administration of – is
contraindicated and elective dental care should be deferred.
epinephrine
Hashimoto’s Thyroiditis
• Autoimmune reaction against thyroid gland destroys
gland rather than stimulating it.
Most common cause of hypothyroidism
Hashimoto’s Thyroiditis
Hashimoto’s Thyroiditis
Most patients first exhibit autoimmune
“thyroiditis,”
thyroid inflammation
Hashimoto’s Thyroiditis
Inflammation leads to fibrosis of thyroid resulting in
decreased secretion of thyroid hormone.
Hypothyroidism due to low —
iodine
In hypothyroid states:
Goiter: — deficiency
No goiter: — deficiency
iodine
TSH
Myxedema
• Seen in severely
hypothyroid patients
Myxedema
Increased quantities of hyaluronic acid and chondroitin sulfate bound with protein plus water accumulate in skin.
Other characteristics of
hypothyroidism:
low BMR, mental capacity, body temp., appetite, HR, RR, BP; anemia, weakness, lethargy, wt. gain; increased cholesterol and blood lipids
Myxedema tx
thyroxine (T4)
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.
Cretinism
• Thyroid hormones required for
postnatal brain maturation.
Cretinism
Results from: (2)
– Congenital absence of thyroid gland (congenital cretinism) – Iodine deficient diet (endemic cretinism): most common cause worldwide
Cretinism causes
physical and mental
retardation of neonates
in Cretinism, skeletal growth is more inhibited than
soft tissue growth (obese,
stocky and short with large
protruding tongue)
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
Patients with hypothyroidism are sensitive to (2), so these medications should be
used sparingly
central nervous
system depressants and barbiturates
phosphate storage
85%
14-15%
1%
85% bones,
14-15% in cells
less than 1% in the EC fluid (HPO42- and H2PO4-)
Changes in the phosphate level of the EC fluid to –X normal does not
cause major immediate effects.
2-3
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
Calcium:
– Too low =
– Too high =
– Too low = neuronal hyper-excitability (tetany)
– Too high = neuronal depression
Control points for calcium and phosphate (3)
- Absorption – via intestines
- Excretion – via urine (calcium and phosphate) and feces (calcium only)
- Temporary storage – via bones (hydroxyapatite) Ca10 (PO4)6 (OH)2
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)
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.
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
Vitamin D3 & Parathyroid Hormone
Stimulate
Bone Matrix Resorption increase plasma calcium
Calcitonin Stimulates
Bone Matrix Deposition & Inhibits Osteoclasts
decreases plasma calcium
— 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
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.
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
Parathyroid Glands
Four pea-sized glands on the posterior
surface of the thyroid gland.
Parathyroid Hormone (PTH) • Secreted by the
Chief Cells
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
↓ ECF Ca2+ concentration
increase rate of PTH secretion hypertrophy of parathyroid gland o Pregnancy o Rickets o Lactation
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
Increases Plasma Calcium (3)
- Bone Resorption
- Reabsorption of Calcium
by Renal Tubules which
reduces excretion - Converts 25-
hydroxycholecalciferol to
1,25-
dihydroxycholecalciferol
(Vitamin D/Calcitriol),
which causes intestinal
calcium absorption.
Decrease Plasma Phosphate (1)
- Decreased reabsorption
by renal tubules leading
to increased urinary
excretion
Calcitonin
Peptide hormone secreted by parafollicular cells (C cells) of the thyroid gland
Calcitonin is released in response to
elevated
free plasma Ca2+
Calcitonin lowers
plasma Ca2+ by decreasing activity of osteoclasts, thus decreasing bone resorption
Calcitonin: not a major controller of – in humans
calcium
Primary Hyperparathyroidism
Excess PTH secretion due
to a parathyroid gland
tumor
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).
Secondary Hyperparathyroidism
• High PTH levels occur as compensation for hypocalcemia
not due to primary abnormality of parathyroid glands
Causes of hypocalcemia: (2)
– Vitamin D deficiency
– Chronic renal disease-cannot synthesize Vit D3
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
Primary Hypoparathyroidism:
Less common-often results from accidental
surgical
parathyroid gland removal
Parathyroid gland removal decreases plasma Ca++
levels from – to –
10 mg/dL to 6-7 mg/dL
Hypocalcemia increases membrane Na+
permeability leading to (3)
neuromuscular excitability &
muscle spasms & tetany
Spasm of laryngeal muscles obstructs respiration
causing — unless appropriate treatment applied
death
