Part 3: Metabolism Regulation

Endocrine System

Thyroid Gland

Location: base of neckventral surface of tracheaBelow & anterior to larynx

One of the largest endocrine glands in the body

Functional Unit: Follicle

Thyroid Gland

Structure:Two lobes4 cm long, 1-2 cm

wideconnected by a

narrow neck (isthmus)

Color: Red / BrownProduces thyroid

hormones

Thyroid Hormones: T3 and T4T4: Thyroxine / Tetraiodothyronine T3: TriiodothyronineRequires iodination

Comparing T3 and T4

T3 (Triiodothyronine) T4 (Thyroxine)

# of Iodine atoms 3 4

% in blood 0.3% 0.03%% produced by thyroid glands ~ 20% ~ 80%

Potency 4X more than T4 Not very

Half Life Span Shorter (1-2.5 d) Longer (5-7 d)

Main Purpose Regulate basal metabolic processes Conversion to T3

Questions

Why is more T4 made than T3?Why have T4 at all when T3 is so

much more effective?

Thyroid Hormones PropertiesPeptide hormone

Derived from the amino acid tyrosineNot very soluble in bloodHydrophobic and will diffuse into cells

Thyroid hormone receptorIntracellular, in nucleusHas greater affinity for T3 than T4

Thyroid Hormones FunctionAct on nearly every cell in the bodyRegulates metabolism

Increase glucose metabolism Increase protein synthesis Increase oxygen consumption (blood pressure,

heart rate)Regulates growth and tissue differentiation

DigestionReproductionBone growthMuscle toneDevelopment of nerve cells

Thyroid Regulation

Stimulus: change in metabolic rate (decreased metabolism)

Detected by hypothalamus

http://eso-cdn.bestpractice.bmj.com/best-practice/images/bp/en-gb/1121-2-iline_default.gif

Thyroid Regulation:Neuroendocrine pathway

Location HormoneHypothalamus

TSH Releasing Hormone / Thyrotropin releasing hormone (TRH)

Anterior Pituitary

Thyroid Stimulating Hormone (TSH)

Thyroid gland Thyroid hormones T3 & T4

Thyroid Regulation: FeedbackHigh levels of

T3/T4 in blood turn off production of TRH and TSH

http://yaplog.jp/cv/miharu_akimoto/img/21/img20090310_1_p.jpg

decreased metabolismIncreased blood sugar

Anterior pituitary release TSH

Hypothalamus release TRH

increase sugar metabolism

Thyroid Regulation

Thyroid gland released T3/T4

Thyroid Regulation: Feedback

Stimulus Low T3/T4 High T3/T4

Effect on TRH Stimulated Inhibited

Effect on TSH Increase InhibitedEffect on T3/T4 Increase Decrease

Thyroid Disorders

HyperthyroidismPlummer’s diseaseGrave’s disease

HypothyroidismHashimoto’s thyroiditis

Hyperthyroidism: Goiter

enlarged thyroid gland due to overactivity

Cause: Iodine deficiency

Low iodine levels means low levels of T3/T4

Body tries to compensate by working the thyroid gland more to make more T3/T4

Hyperthyroidism Symptomshigh T4 (thyroxine) releasehigh glucose metabolism:

weight loss with increased appetiteanxietyincreased heat release

Cause: Nodules(Plummer’s Disease)Nodule: small lumpstoxic multinodular goiter (many

nodules)

http://www.phoenity.com/diseases/goiter.html

Cause: Autoimmunity (Grave’s Disease)Thyroid stimulating immunoglobulin

(TSI)An antibody that targets TSH receptors

to stimulate TSH secretion (from anterior pituitary)

TSI not subject to negative feedback8x more common in womenbetween ages 20 – 40

Grave’s Disease Symptomsprotruding eyeseye irritation and double vision

Hyperthyroidism: Other CausesOveractive thyroid gland that produces

too many thyroid hormones without requiring stimulation by TSH

Inflammation of the thyroid (thyroiditis)Pituitary tumorsToo much thyroid hormone medicationExcessive intake of iodine

Hyperthyroidism Treatment:Drug TherapyAnti-thyroid drugs (suppressive

medication)Block amount of thyroid hormone in

the blood streamPrevent iodine from entering thyroid

gland

Hyperthyroidism Treatment:Radioactive Iodine TherapyGiven when drug therapy failsRadioactive iodine-131Damages thyroid cells over timeThyroid gland shrinks returning

thyroid hormone to normal level.

Hyperthyroidism Treatment:SurgeryThyroidectomy: removal of all or

some parts of the thyroid glandPost-surgery, thyroid replacement

drugs may be necessary, depending on how much of the thyroid gland is left.

Hypothyroidism Symptomslow thyroxine releaselow glucose metabolism

weight gainfatiguedecreased heart release

4x more common in women than men

usually between ages 35 – 60

Hypothyroidism

Cause: Autoimmunity(Hashimoto’s Thyroiditis)Immune system attacks thyroid

glandInflammation of the thyroid gland

20x more common in womenbetween the ages 30 – 50Treatment: thyroid hormone

supplements

Hypothyroidism: Other CausesIodine deficiencyThyroid gland dysfunction:

producing too little thyroid hormones

After radiation therapy with radioactive iodine

After a thyroidectomy

Comparing Symptoms

Hyperthyroidism Hypothyroidism

Weight Loss but good appetite GainBody Function

Increased bowel movementLight/absent menstrual periods

ConstipationHeavy menstrual periods

Temperature

Warm/moist skin, Feel hot

Feel cold

Neurological

Fatigue, InsomniaIrritability, Nervousness

FatigueSlowed thinking

Others Bulging eyes, goiter Dry skin

Calcium Regulation

Antagonistic hormones:PTHcalcitonin

Calcium Storage

99% stored in bonesIn cells: mitochondria

and ERIn skeletal muscles:

sarcoplasmic reticulum (SR)

http://www.bio.miami.edu/~cmallery/150/neuro/SR2.jpg

Calcium Function

MusclesCa levels inside muscle cells change

when muscles contractNerves

Ca stimulate release of neurotransmitters

Bone Cells

Osteoblast: bone-forming cells, take Ca from blood to build into bones

Osteoclast: break down Ca in bones and release into blood

Parathyroid Gland

4 small oval shaped glands

Located behind the thyroid glands

Each lobe of thyroid gland is adjacent to 2 parathyroid gland

Secretes parathyroid hormone (PTH)

Parathyroid Hormone (PTH)Peptide hormone Continuously produced (tonic

secretion) Stimulated by a decrease in blood

calcium (hypocalcemia)

PTH Targets

BoneInduces osetoclastDecompose bone to release stored Ca

into bloodKidney

Stimulates reabsorption of calciumConverts vitamin D precursor to active

vitamin D

Vitamin D

Steroid hormoneCan be ingested in food or formed in

skin when exposed to sunlightActivated form of vitamin D

reinforces the effect of PTHIncrease calcium in blood

Vitamin D Targets

Bone: release CaIntestine: Stimulates absorption of

calcium

Calcium Regulation

Low blood Ca(hypocalcemia)

PTH releasedBy parathyroid glands

Activation ofVitamin D

BoneKidney Intestine

Increasereabsorption

Stimulate osteoclast

Decomposebone

Increaseabsorption

Calcitonin

Peptide hormoneSecreted by thyroid glandStimulated by increase of blood

calcium (hypercalcemia)Antagonist of PTH: decreases blood

calcium

Calcitonin Targets

BoneStimulates Ca uptake into bones Inhibits osteoclastsLess bone tissue removal

Kidney Inhibits Ca reabsorption Increases rates of Ca loss by urinatinghigher concentration of Ca in urine

Intestine inhibits Ca absorption

http://www.bio.miami.edu/~cmallery/150/physiol/c45x1ca-regulation.jpg

Hypoparathyroidism

Causes:absent parathyroid from birthaccidental removal upon thyroid removal

Symptoms:decreased Ca levels in blood (hypocalcemia)sensitive nervesuncontrollable spasms of the limbs

Treatmentdaily calcium and vitamin D supplements

Hypocalcemia Symptoms

Tetanyan increased excitability of the nerves

(nerves are more likely to respond to less intense stimuli)

results in uncontrollable, painful spasms of the face, hands, arms, and feet

Seizures

hypocalcemia

parathyroid gland release PTHincreased Ca2+ levels

increased Ca2+ uptake in intestines (diet) &

kidneys (reabsorption)

increases osteoclast activity

activation of vitamin D; required for Ca2+ absorption

Hypocalcemia

Hyperparathyroidism

Causes:tumors on the parathyroid

glandSymptoms:

kidney stonesaches & painsosteoporosisdepression & fatigue

Treatment:removal of parathyroid tissue

Hypercalcemia SymptomsStones (Kidney Stones)Bones (Bone Pain)Groans (Constipation)Moans (peptic ulcer, pancreatitis)Overtones (Depression/ Confusion)

hypercalcemia

thyroid gland release calcitonindecreased Ca2+ levels

inhibits Ca2+ absorption by intestines

decreases osteoclast activity

Hypercalcemia

Osteoporosis

Loss of density in bones, leading to fragile bones

CausesHyperparathyroidism

Hyperactive Parathyroid (high levels of PTH)Hypovitaminosis D

Lack of Vitamin D in diet Decrease in enzyme catalyzing Vitamin D

Over activity of osteoclasts

Osteoporosis Symptoms

increase risk of bone fracturesJoint painkyphosis (hunchback)

http://www.youtube.com/watch?v=rHyeZhcoZcQ&feature=related