Lecture 77 Flashcards
Thyroid Metabolic Hormones
1
Q
The thyroid gland is located
A
above the heart and below the chin, around the larynx.
2
Q
excessive TH on muscles:
A
Muscle becomes weakened with excessive TH, because of excessive protein catabolism.
3
Q
thyroiditis
A
inflammation of the thyroid gland
4
Q
effect lack of TH on gastrointestinal tract:
A
constipation
5
Q
thyroid gland ideal shape
A
looks like a butterfly
6
Q
Proximal to the thyroid gland are the parathyroid glands of which there are
A
four
7
Q
The thyroid gland primarily produces and secretes __ major hormones
A
two
8
Q
The thyroid gland primarily produces and secretes two MAJOR* hormones:
A
- Thyroxine (T4 ) represents 93% of the secretion from the thyroid gland.
- Triiodothyronine (T3 ) represents 7% of the secretion from the thyroid gland.
9
Q
Which hormone represents 93% of the secretion from the thyroid gland (1/2 of the major secretions)
A
Thyroxine (T4 )
10
Q
Triiodothyronine (T3 ) represents what percentage of the secretion of the thyroid gland
A
7% of the secretion from the thyroid gland
11
Q
thyroid gland primarily produces and secretes two (T4 and T3) but also MAKES and SECRETES:
A
calcitonin
12
Q
Calcitonin (the most minor secretion of the throid gland), plays a minor role in maintaining (2)
A
Ca2+ and phosphate regulation
13
Q
The two thyroid hormones (T3 and T4) are required to maintain
A
the basal metabolic rate (BMR)
14
Q
T3 and T4 hormone formation (5 Steps)
A
(1) Thyroxine (T4) and triiodothyronin (T3) are formed by combining TWO TYROSINES with either 4 or 3 iodide molecules
(2) Peroxidase is required to add iodine to tyrosine
(3) after synthesis, TH remains attached to thyroglobulin (each thyroglobulin contains 70 amino acids)
(4) Thyroglobulin containing TH is stored in the follicular coloid
15
Q
The BMR represents
A
the chemical reactions in your body that consume nutrients and oxygen to produce energy, heat and carbon dioxide.
16
Q
Release mechanism of T3 and T4 (9) :
A
(1) Thyroid cells (aka follicular cells) send out pseudopod extensions to engulf small portions of the colloid
(2) lysosomes fuse with these vesicles, releasing enzymes that break down thyroglobulin
(3)Proteinases digest thyroglobulin, releasing thyroxine (T4) and triiodothyronine (T3)
(4)T4 and T3 diffuse through thyroid cells into blood
(5) iodides are recycled within the gland cell for additional TH production (using deiodinase enzyme)
(6) Recycled products are mono-iodo thyronine (MIT) and di-iodothyronine (DIT).
(7) 93% of TH released is thyroxine, and 7% is triiodothyronine. A tiny bit of reverse T3 (RT3) is also secreted, but its function is not known.
(8) Thyroxine is slowly deiodinated to triiodothyronine, making T3 the primary hormone used by tissues.
17
Q
If there is a chronic lack of thyroid hormones, it can decrease the metabolic rate to
A
40 - 50% below normal
18
Q
symptoms of a chronic lack of thyroid hormones:
A
make someone feel cold and gain weight possibly.
19
Q
If there is chronic excessive TH it can
A
increase the metabolic rate to 60 - 100% above normal
20
Q
symptoms of somebody with chronic excessive TH:
A
make someone feel too hot and loose body weight possibly.
21
Q
up to __ is required to produce normal quantities of thyroid hormones
A
1 mg/ week of iodide
22
Q
iodides are ingested:
A
orally
23
Q
iodides are ingested orally and absorbed from __ into __
A
iodides are absorbed from gastrointestine tract into blood circulation
24
Q
the absorption of iodide is so poor that it has to be :
A
chemically modified before being absorbed in the bloodstream (still, most of it gets excreted)
25
When iodide reaches the thyroid gland, there are __
when iodide reaches the thyroid gland, there are iodide pumps to actively transport the iodides from the blood into the thyroid gland
26
What is iodide trapping
When iodide reaches the thyroid gland, there are iodide pumps to actively transport the iodides from the blood into the thyroid gland
27
is iodide trapping effective?
iodide trapping is not very effective, only 20% of the iodides in blood are taken in by thyroid gland and the rest of them are excreted by kidney
28
compare iodide concentration in the blood versus in the thyroid cell
The concentration of iodide is 30x higher in the thyroid cell than in the blood
29
Major, and perhaps only, part of the body that traps and requires iodide.
The thyroid
30
The thyroid gland is composed of many:
follicles filled with colloid
31
The thyroid gland is composed of many follicles (100 to 300 μm in diameter) filled
with colloid
32
colloid (in the follicles that make up the thyroid glans) is mainly composed of:
glycoprotein called thyroglobulin
33
the thyroid gland is composed of many follicles filled with collid, the colloid is composed of the glycoprotein thyroglublin, Thyroglobulin contains
Thyroid hormones (TH)
34
c cells secrete
calcitonin
35
follicular cells secrete
thyroid hormone
36
A large glycoprotein molecule called thyroglobulin can be synthesized by
Golgi apparatus in the thyroid cell
37
Thyroxine (T4 ) and triiodothyronine (T3 ) are formed by:
By combining two tyrosines with either 4 or 3 iodide molecules
(peroxidase is needed to add iodide to the tyrosines -> if the peroxidase system is blocked, or there is not enough iodide, the formation of TH will stop)
38
___ is needed to add iodide to the tyrosines
Peroxidase
39
After Th is synthesized, it remains attached to
the thyroglobulin
40
If the peroxidase system is blocked, or there is not enough iodide, the formation of TH will
stop
41
thyroxine (t4) and throglobulin (T3) are synthesized from what 3 components:
(1) two tyrosines
(2) 4 or 3 iodide molecules
(3) peroxidase
42
Each thyroglobulin contains __ amino acids
70 tyrosine amino acid
43
The thyroglobulin that contains TH will:
secrete into follicular colloid (follicles) to be stored
44
The stored TH is normally sufficient to supply for the body for:
2 to 3 months
45
if the synthesis of TH ceases, the effects of deficiency will __
not be observed for several months
46
Describe the process of the release of thyrosine and triiodothyronine from thyroid gland (5 steps):
(1) the surface of the thyroid cell send out pseudopod extensions that close around small portions of colloid
(2) these colloid-containing vesicles fuse with lysosymes inside the cell
(3): T4 (thyroxine) and T3(triiodothyronine) are cleaved from thyroglubulin during this digestion
(4) the free T3 and T4 molecules then diffuse out of the thyroid cell and into the bloodstream, where they exert systemic metabolic activities
47
what is iodide recycling process?
(1) during the breakdown of thyroglobulin, T4 and T3 are released along with iodide
(2) these iodines are recycled within the thyroid follicular cells to be reused for the synthesis of new thyroid hormones
**
48
What is essential for iodide recycling?
the enzyme deiodinase
49
What will a lack of deiodinase do?
a lack of deioidinase impairs the recycling of deiodide, leading to iodide defficiency within the gland despite normal intake, thereby reducing thyroid hormone production over time
50
What are the products of the recycling process (2)?
the recycled products are mono-iodo thyronine (MIT) and di-iodothyronine (DIT), they are just one tyrosine attached to one or two iodides respectively
51
Percentage of each hormone released by the gland:
93% of TH released from gland is thyroxine and 7% of TH is triiodothyronine. A tiny bit of reverse T3
(RT3), which is a chemical mirror-image of T3, is also secreted but its function is not known.
52
What is the thyroid hormone mainly used by the tissues?
In few
days most of the thyroxine is slowly deiodinated to become triiodothyronine (removal of one iodines
from T4). Therefore, the hormone finally used by the tissues is mainly T3.
53
Once the T4 and T3 enter in the blood, T4 and T3 immediately combine with:
several plasma binding proteins (3)
54
Once the T4 and T3 enter in the blood, T4 and T3 combine immediately with several plasma-
binding proteins including:
1. Thyroxine-binding globulin ( mainly )
2. Thyroxine-binding prealbumin ( less so )
3. Albumin ( less so )
55
Rate of release of T3 in blood to tissue cells:
Half of T3 in blood is released to tissue cells in one day
56
Rate of release of T4 in blood
Half of T4 is released in 6 days, because the plasma-binding protein has higher affinity for T4
57
Why does T4 have a slower release than T3 in blood?
the plasma-binding protein has higher affinity for T4
58
When the T4 and T3 enter tissue cells, they bind with:
intracellular proteins, and will be used by the tissue cell slowly over days or weeks
59
When the T4 and T3 enter tissue cells, they bind with intracellular proteins, which binds more strongly between the two hormones?
T4
60
latency period of t4
2-3 days
61
when does T4 activity reach a maximum
10-12 days
62
T4 decreases with a half life of:
15 days (can be as long as 2 months)
63
The action of T3 occurs __ as fast as those of T4
The action of T3 occurs 4 times as fast as those of T4
64
the latent period of T3
6-12 hours
65
the maximum cellular activity of T3 occurs when
2-3 days
66
Because the plasma-binding protein has higher affinity for thyroxine, release of __ is slower than
that of __.
T4 slower than T3
67
The general effect of thyroid hormone is to cause:
nuclear transcription of genes for synthesizing large number of substances in the cells
68
the general effect of thyroid hormone is to cause nuclear transcription of genes for synthesizing large number of substances in the cells including (4):
(1) Enzymes
(2) Structural Proteins
(3) Transport Proteins
and other substances
69
In what proportions do the thyroid hormones bind on their receptors?
Before the hormone acts on the genes, almost all the thyroxine is deiodinated to triiodothyronine,
then T3 bind with intracellular thyroid hormone receptors in the nucleus. More than 90% of the
thyroid hormone that binds to receptors is T3 , less than 10% of thyroid hormone that binds to
receptors is T4
70
When thyroid hormone attaches to the thyroid hormone receptors, the complex is then attached
to the DNA genetic strands, then what happens?
receptors become activated and initiate the transcription process -> different types of messenger RNA are formed -> many new types of proteins are formed by RNA translation on cytoplasmic ribosomes
71
most of the actions of thyroid hormone result from:
the enzymatic and other functions of these new proteins
72
effect of thyroid hormones on mitochondria (2):
(1) increase the number of mitochondria
(2) increase the total membrane surface area (size) of mitochondria --> increase the formation rate of ATP to energize cellular function
73
thyroid hormone stimulates __ aspects of carbohydrate metabolism because of __
thyroid hormone stimulate all aspects of carbohydrate metabolism because of the increase of metabolic enzymes
74
Effect of thyroid hormones on carbohydrate metabolism
Stimulates all aspects of carbohydrate metabolism because of the increase of metabolic enzymes.
The effects include as follows (5):
(1) Increase absorption rate of glucose from gastrointestinal tract.
(2) Increase uptake rate of glucose by cells (independent of insulin)
(3) Enhance glycolysis (use of glucose for energy through anaerobic conversion of glucose to
lactic acid).
(4) enhance gluconeogenesis ( formation of new glucose ).
(5)Increase insulin secretion, which also promotes glucose uptake.
(6)TH decreases glycogen stores in the liver and skeletal muscle, this is called
glycogenolysis, it allows more glucose to enter the circulation. reference
75
glycogenolysis,
TH decreases glycogen stores in the liver and skeletal muscle
76
Effects of thyroid hormone on fat metabolism:
(1)Thyroid hormone stimulates lipolysis:
Breakdown of triglycerides into free fatty acids (FFAs) and glycerol. --> This leads to mobilization of fatty acids, increasing FFA concentration in the plasma.
(2)TH accelerates the oxidation (use for energy) of these FFAs by peripheral tissues.
77
Effect of Thyroid Hormone on Fat Metabolism: In the Plasma
Despite the rise in FFAs, TH decreases overall plasma levels of cholesterol, phospholipids, and triglycerides.
This occurs because TH increases cholesterol secretion into bile and promotes its excretion via feces.
78
Effect of Thyroid Hormone on Fat Metabolism: In Hepatic (Liver) Cells
TH promotes de novo lipogenesis:
The synthesis of new triglycerides from glucose, glycerol, and FFAs.
“Thyroid hormones are a well-known inducer of hepatic de novo lipogenesis.”
79
Thyroid hormones are a well-known inducer of hepatic
de novo lipogenesis
80
hyperthyroidism effect on fat metabolism in liver:
in hyperthyroidism, fatty acid oxidation surpasses synthesis, resulting in a net decrease in liver triglyceride content.
81
*****Effect of thyroid hormone on fat metabolism: If there is a lack of TH (hypothyroidism) it causes
excessive deposition of fat in liver.
This is due to the lower amount of catabolism in the liver
82
Effect of thyroid hormone on fat metabolism: prolonged hypothyroidism causes:
severe arteriosclerosis due to
accumulation of cholesterol.
83
arteriosclerosis
hardening of arteries
84
Effect of Thyroid Hormone on Protein Metabolism
1. At Normal (Physiological) Levels (3)
(1)promotes protein synthesis in various tissues. which in turn:
(2) anabolic effect supports tissue growth, maintenance, and increased metabolic activity.
(3) Enhances enzyme production and cellular function in response to elevated metabolic demand.
85
Effect of thyroid hormone on protein metabolism.At Excess Levels (Hyperthyroidism)
If TH is in excess, it will increase **proteolysis**, since the **tissues** are active they
**need protein turnover to increase.**
This is a** catabolic effect**, but it helps with growth
to occur properly. Over time though, it **can** weaken the muscle in a hyperthyroid
patient.
86
Effect of thyroid hormone on Vitamin Metabolism
* Vitamins are essential parts of enzymes or coenzymes. TH **increases quantities of
enzymes**, in turn, **increase the need for vitamins.**
* Increase of TH **can cause a relative vitamin deficiency** unless the increased quantities of
vitamins are available.
87
The effect of thyroid hormone in increasing active transport of ions through cell membrane
Thyroid hormone **activates membrane enzymes**, particularly:
Na⁺/K⁺-ATPase, also known as the **sodium-potassium pump.**
This leads to an** increased rate of active transport of Na⁺ and K⁺ ions** across cell membranes.
**Active transport consumes ATP**, and as a result, **increases heat production** (this contributes to TH’s role in regulating basal metabolic rate).
TH also increases membrane permeability to Na⁺ ions, causing more Na⁺ to leak into the cell.
This leak stimulates the Na⁺/K⁺-ATPase to work harder to maintain ionic balance.
The combined effect is:
Greater ATP consumption
Increased metabolic rate
Enhanced thermogenesis (heat generation)
88
The effect of thyroid hormone on growth
* Lack of TH ( hypothyroid ) causes
growth rate retarded for growing children
89
The effect of thyroid hormone on growth:Excessive TH ( hyperthyroid ) causes
rapid skeletal growth, early bone mature for
children
90
The effect of TH on the cardiovascular system: increases 5 things
* Increase blood flow and cardiac output because of the rapid utilization of oxygen for
increased metabolism.
* Increase heart rate because of the increase of cardiac output.
* Increase the strength of the heart beat ( because of increased enzymatic activity ).
* Increase slightly blood volume because of vasodilation which allows increased quantities
of blood to collect in the circulatory system.
* Increase arterial pressure because of the increased blood flow
91
The Effect of thyroid hormone on respiration
Increase **rate** and **depth** of respiration because of increased rate of metabolism ➔
**increased use of oxygen.**
92
The effect of TH on gastrointestinal tract
**Increase secretion rate** of digestive juice and motility of gastrointestinal tract.
93
The effect of TH on gastrointestinal tract: Excessive TH causes
diarrhea
94
The effect of thyroid hormone on central nervous system
Increase brain activity ( cerebration ).
95
The effect of thyroid hormone on central nervous system: Excessive TH ( hyperthyroid ) cause
nxiety, extreme worry and paranoia.
96
The effect of thyroid hormone on muscle function: excess
* Hyperthyroid causes muscle tremor because of increased reactivity of neuronal synapses
in the areas of the spinal cord that control muscle tone.
97
The regulatory mechanism for controlling TH secretion is as follows.
A hypothalamic hormone called thyrotropin-releasing hormone (TRH) is secreted by nerve
endings in the median eminence of the hypothalamus,
➔ TRH is transported to anterior pituitary through the hypothalamic-hypophysial
portal vessel,
➔ TRH bind with TRH receptors on the pituitary cell membrane,
➔ Activates phospholipase second messenger system to produce
phospholipase C and other second messenger products
➔ Cause thyrotropin secreting cell in the anterior pituitary to produce and release
thyroid-stimulating hormone (TSH/thyrotropin ),
➔ TSH bind with TSH receptor on basal membrane surface of thyroid cell,
98
TSH Cause increased release of T4 and T3 into blood by increasing the following (4):
* Proteolysis of thyroglobulin
* Activity of iodide pump
* Iodination of tyrosine for forming TH
* Size and number of thyroid cells
99
The secretion of TSH from anterior pituitary is controlled by feedback regulation mechanism as
follows (direct pathway)
* The concentration level of TH in the body fluid will feedback directly to anterior
pituitary.
* Increased TH will directly affect anterior pituitary to cause decrease of secretion of TSH
➔ decrease the release of TH ➔ eventually to maintain a constant
concentration of free TH in the circulatory body fluids.
100
The secretion of TSH from anterior pituitary is controlled by feedback regulation mechanism as
follows: indirect pathway:
Increased TH ➔ increased metabolic function ➔ increased heat production
➔ increased body temperature ➔ affect on hypothalamus, which is the body
temperature controlling centre ➔ cause decreased release of TRH from
hypothalamus ➔ decreased release of TSH from anterior pituitary ➔
decreased release of TH from thyroid cells
101
Hyperthyroidism: 3 types:
Toxic Goiter, Thyrotoxicosis, Grave's Disease
102
In patients with hyperthyroidism the thyroid gland is increased to
2 to 3 times normal size
103
In patients with hyperthyroidism,The
number of thyroid cell is
increased even several times more than the size increased
104
In patients with hyperthyroidism,the
secretion rate increases:
several fold ( 5 - 15 times normal ).
105
Hyperthyroidism:Principal Causes
Caused by autoimmunity. Presumably, in the history of the person an excessive amount of
thyroid cell antigens has been released from the thyroid cells. This causes the formation of
antibodies against thyroid gland itself. They are called thyroid stimulating immunoglobulins
(TSI)
106
thyroid stimulating immunoglobulins
(TSI)
antibodies against thyroid gland itself
107
thyroid-stimulating immunoglobulin mechanism that causes hyperthyroidism:
TSI is an autoantibody that mimics thyroid-stimulating hormone (TSH).
It binds to the TSH receptors on thyroid follicular cells, activating the cAMP second messenger system, just like TSH.
However, TSI has a much longer stimulatory effect:
TSI stimulates the thyroid gland for up to 12 hours,
TSH stimulates for only about 1 hour.
This prolonged stimulation by TSI leads to:
Excessive thyroid hormone (TH) secretion (T₄ and T₃),
Thyroid gland enlargement (goiter).
As a result of elevated TH levels, there is negative feedback inhibition on the anterior pituitary,
→ causing suppressed TSH production.
108
Thyroid adenoma ( tumor ) developed in the thyroid tissue can also cause
over-secretion of TH.
109
consequences of thyroid adenoma:
A thyroid adenoma is a benign tumor that can develop within thyroid tissue.
It may cause autonomous (uncontrolled) over-secretion of thyroid hormones (T₄ and T₃), independent of TSH regulation.
As a result, thyroid hormone levels in the blood become elevated, leading to hyperthyroidism-like symptoms.
This elevated TH exerts negative feedback on the anterior pituitary,
→ causing suppressed TSH production.
110
Symptoms and Consequences of Hyperthyroidism
* High state of excitability
* Intolerance to heat
* Increased sweating
* Mild to extreme weight loss
* Different degrees of diarrhea
* Muscle weakness
* Nervousness
* Exophthalmos ( protrusion of eyeballs )
* Extreme fatigue
* Inability to sleep
* Tremor of hands
19
* Other psychiatric disorders
111
Symptoms and Consequences of Hypothyroidism
* Fatigue
* Extreme somnolence (feeling sleepy)
* Extreme muscular sluggishness (slow to respond)
* Slow heart rate
* Decreased blood volume and cardiac output
* Increased weight
* Constipation
* Mental sluggishness
* Depressed growth of hair
* Scaling of skin
* Edematous appearance ( myxedema )
* Increase of blood cholesterol ➔ arteriosclerosis
112
Hypothyroidism: Autoimmune Destruction
Most common cause of hypothyroidism.
Autoimmune response destroys thyroid tissue rather than stimulating it.
Begins as thyroiditis (inflammation) → progressive deterioration → fibrosis of the gland.
Leads to reduced or absent thyroid hormone secretion.
113
Iodide Deficiency (Endemic Goiter)
Insufficient iodide intake prevents synthesis of T₄ and T₃.
Thyroglobulin production continues, but lacks thyroid hormone content.
No negative feedback to suppress TSH, so:
TSH levels rise, overstimulating the thyroid.
Thyroid follicles enlarge, leading to a massive goiter (10–20× normal size).
But still, little or no TH is produced, worsening hypothyroidism.
114
idiopathic Nontoxic Colloid Goiter
Enlarged thyroid without iodide deficiency.
Likely caused by mild thyroiditis, leading to slight hypothyroidism.
This triggers increased TSH secretion, stimulating the growth of the non-inflamed portion of the gland.
Exact cause is unknown ("idiopathic").
115
Genetic or Enzymatic Defects in TH Synthesis (4):
Deficient iodide trapping → low iodide entry into follicular cells.
Deficient peroxidase system → iodide not oxidized into usable iodine.
Defective coupling of iodinated tyrosines → T₄ and T₃ not formed.
Lack of deiodinase enzyme → iodide can't be recycled from thyroglobulin
116
Deiodinase enzymes act on
MIT and DIT
117
Deiodinase enzymes act on MIT AND DIT to:
Remove iodide (I⁻) from them.
Recycle the iodide back into the thyroid follicular cells.
118
