Post on 29-Dec-2015
Gross Anatomy of Thyroid Gland
Thyroid Gland
• Two lateral lobes connected by median mass called isthmus
• Composed of follicles that produce glycoprotein thyroglobulin
• Colloid (thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone
• Parafollicular cells produce the hormone calcitonin
Figure 16.9 The thyroid gland.
Hyoid bone
Thyroid cartilage
Common carotidartery
Inferior thyroidartery
Trachea
Aorta
Gross anatomy of the thyroid gland, anterior view
Epiglottis
Superior thyroidartery
Isthmus ofthyroid gland
Left subclavianartery
Left laterallobe of thyroidgland
Colloid-filledfollicles Follicular cells
Parafollicular cells
Photomicrograph of thyroid glandfollicles (145x)
Thyroid Hormone (TH)
• Actually two related compounds– T4 (thyroxine); has 2 tyrosine molecules + 4
bound iodine atoms
– T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms
• Affects virtually every cell in body
Thyroid Hormone
• Major metabolic hormone
• Increases metabolic rate and heat production (calorigenic effect)
• Regulation of tissue growth and development– Development of skeletal and nervous systems– Reproductive capabilities
• Maintenance of blood pressure
Synthesis of Thyroid Hormone
• Thyroid gland stores hormone extracellularly
• Thyroglobulin synthesized and discharged into follicle lumen
• Iodides (I–) actively taken into cell and released into lumen
• Iodide oxidized to iodine (I2),
• Iodine attaches to tyrosine, mediated by peroxidase enzymes
Synthesis of Thyroid Hormone
• Iodinated tyrosines link together to form T3 and T4
• Colloid is endocytosed and combined with lysosome
• T3 and T4 are cleaved and diffuse into bloodstream
Figure 16.10 Synthesis of thyroid hormone. Slide 1
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
2
3
4
5
6
7
Golgiapparatus
Iodide (I−)
RoughER
Capillary
Iodide (I–) is trapped (actively transported in).
Lysosome
Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream.
Thyroglobulin colloid is endocytosed and combined with a lysosome.
Iodinated tyrosines are linked together to form T3 and T4.
Iodide is oxidized to iodine.
Iodine is attached to tyrosine in colloid, forming DIT and MIT.
To peripheral tissues
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Thyro-globulincolloid
T3
T4
T3
T4
T3
T4
IodineDIT MIT
Colloid
Figure 16.10 Synthesis of thyroid hormone. Slide 2
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
Figure 16.10 Synthesis of thyroid hormone. Slide 3
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
2Iodide (I−) Iodide (I–) is trapped (actively transported in).
Figure 16.10 Synthesis of thyroid hormone. Slide 4
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
2Iodide (I−) Iodide (I–) is trapped (actively transported in).
Iodine
3 Iodide is oxidized to iodine.
Figure 16.10 Synthesis of thyroid hormone. Slide 5
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
2Iodide (I−) Iodide (I–) is trapped (actively transported in).
Iodine
3 Iodide is oxidized to iodine.
4 Iodine is attached to tyrosine in colloid, forming DIT and MIT.
Thyro-globulincolloidDIT MIT
Figure 16.10 Synthesis of thyroid hormone. Slide 6
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
2Iodide (I−) Iodide (I–) is trapped (actively transported in).
Iodine
3 Iodide is oxidized to iodine.
4 Iodine is attached to tyrosine in colloid, forming DIT and MIT.
Thyro-globulincolloidDIT MIT
5 Iodinated tyrosines are linked together to form T3 and T4.
T3
T4
Figure 16.10 Synthesis of thyroid hormone. Slide 7
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
Golgiapparatus
RoughER
Capillary
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Colloid
2Iodide (I−) Iodide (I–) is trapped (actively transported in).
Iodine
3 Iodide is oxidized to iodine.
4 Iodine is attached to tyrosine in colloid, forming DIT and MIT.
Thyro-globulincolloidDIT MIT
5 Iodinated tyrosines are linked together to form T3 and T4.
T3
T4
6
Lysosome
Thyroglobulin colloid is endocytosed and combined with a lysosome.
Figure 16.10 Synthesis of thyroid hormone. Slide 8
Thyroglobulin is synthesized and discharged into the follicle lumen. 1
2
3
4
5
6
7
Golgiapparatus
Iodide (I−)
RoughER
Capillary
Iodide (I–) is trapped (actively transported in).
Lysosome
Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream.
Thyroglobulin colloid is endocytosed and combined with a lysosome.
Iodinated tyrosines are linked together to form T3 and T4.
Iodide is oxidized to iodine.
Iodine is attached to tyrosine in colloid, forming DIT and MIT.
To peripheral tissues
Colloid inlumen offollicle
Thyroid follicular cells
Tyrosines (part of thyroglobulinmolecule)
Thyro-globulincolloid
T3
T4
T3
T4
T3
T4
IodineDIT MIT
Colloid
Transport and Regulation of TH
• T4 and T3 transported by thyroxine-binding globulins (TBGs)
• Both bind to target receptors, but T3 is ten times more active than T4
• Peripheral tissues convert T4 to T3
Transport and Regulation of TH
• Negative feedback regulation of TH release – Rising TH levels provide negative feedback
inhibition on release of TSH– Hypothalamic thyrotropin-releasing hormone
(TRH) can overcome negative feedback during pregnancy or exposure to cold
Hypothalamus
TRH
Anterior pituitary
TSH
Thyroid gland
Thyroidhormones
Target cellsStimulates
Figure 16.8 Regulation of thyroid hormone secretion.
Inhibits
Homeostatic Imbalances of TH
• Hyposecretion in adults—myxedema; goiter if due to lack of iodine
• Hyposecretion in infants—cretinism
• Hypersecretion—Graves' disease
Figure 16.11 Thyroid disorders.
Calcitonin
• Produced by parafollicular (C) cells
• No known physiological role in humans
• Antagonist to parathyroid hormone (PTH)
• At higher than normal doses– Inhibits osteoclast activity and release of Ca2+
from bone matrix– Stimulates Ca2+ uptake and incorporation into
bone matrix
Parathyroid Glands
• Four to eight tiny glands embedded in posterior aspect of thyroid
• Contain oxyphil cells (function unknown) and parathyroid cells that secrete parathyroid hormone (PTH) or parathormone
• PTH—most important hormone in Ca2+ homeostasis
Figure 16.12 The parathyroid glands.
Parathyroidglands
Parathyroidcells(secreteparathyroidhormone)
Capillary
Oxyphilcells
Pharynx(posterioraspect)
Thyroidgland
Esophagus
Trachea
Parathyroid Hormone
• Functions– Stimulates osteoclasts to digest bone matrix
and release Ca2+ to blood – Enhances reabsorption of Ca2+ and secretion
of phosphate by kidneys– Promotes activation of vitamin D (by kidneys);
increases absorption of Ca2+ by intestinal mucosa
• Negative feedback control: rising Ca2+ in blood inhibits PTH release
Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.
Osteoclast activityin bone causes Ca2+
and PO43- release
into blood
Hypocalcemia(low blood Ca2+)
PTH release fromparathyroid gland
Ca2+ reabsorptionin kidney tubule
Activation ofvitamin D by kidney
Ca2+ absorptionfrom food in small
intestine
Ca2+ in blood
Initial stimulus
Physiological response
Result
Homeostatic Imbalances of PTH
• Hyperparathyroidism due to tumor– Bones soften and deform– Elevated Ca2+ depresses nervous system and
contributes to formation of kidney stones
• Hypoparathyroidism following gland trauma or removal or dietary magnesium deficiency– Results in tetany, respiratory paralysis, and
death
Adrenal (Suprarenal) Glands
• Paired, pyramid-shaped organs atop kidneys
• Structurally and functionally are two glands in one– Adrenal medulla—nervous tissue; part of
sympathetic nervous system– Adrenal cortex—three layers of glandular
tissue that synthesize and secrete corticosteroids
Adrenal Cortex
• Three layers of cortex produce the different corticosteroids– Zona glomerulosa—mineralocorticoids– Zona fasciculata—glucocorticoids– Zona reticularis—gonadocorticoids
Figure 16.14 Microscopic structure of the adrenal gland.
Med
ulla
Cort
ex
Capsule
Zonaglomerulosa
Zonafasciculata
Zonareticularis
Adrenalmedulla
Adrenal gland• Medulla
• Cortex
Kidney
Hormonessecreted
Aldosterone
Cortisolandandrogens
Epinephrineandnorepinephrine
Photomicrograph (115x) Drawing of the histology of theadrenal cortex and a portion ofthe adrenal medulla
Mineralocorticoids
• Regulate electrolytes (primarily Na+ and K+) in ECF– Importance of Na+: affects ECF volume, blood
volume, blood pressure, levels of other ions– Importance of K+: sets RMP of cells
• Aldosterone most potent mineralocorticoid – Stimulates Na+ reabsorption and water
retention by kidneys; elimination of K+
Aldosterone
• Release triggered by– Decreasing blood volume and blood pressure– Rising blood levels of K+
Mechanisms of Aldosterone Secretion
• Renin-angiotensin-aldosterone mechanism: decreased blood pressure stimulates kidneys to release renin triggers formation of angiotensin II, a potent stimulator of aldosterone release
• Plasma concentration of K+: increased K+ directly influences zona glomerulosa cells to release aldosterone
• ACTH: causes small increases of aldosterone during stress
• Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion to decrease blood pressure
Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex.
Blood volumeand/or blood
pressure
K+ in blood Stress Blood pressureand/or blood
volume
Hypo-thalamus
Heart
CRH
Anteriorpituitary
Directstimulatingeffect
Initiatescascadethatproduces
Renin
Angiotensin II
ACTH Atrial natriureticpeptide (ANP)
Inhibitoryeffect
Zona glomerulosaof adrenal cortex
Enhancedsecretionof aldosterone
Targetskidney tubules
Absorption of Na+ andwater; increased K+ excretion
Blood volumeand/or blood pressure
Kidney
Primary regulators Other factors
Homeostatic Imbalances of Aldosterone
• Aldosteronism—hypersecretion due to adrenal tumors– Hypertension and edema due to excessive Na+
– Excretion of K+ leading to abnormal function of neurons and muscle
Glucocorticoids
• Keep blood glucose levels relatively constant
• Maintain blood pressure by increasing action of vasoconstrictors
• Cortisol (hydrocortisone)– Only one in significant amounts in humans
Glucocorticoids: Cortisol
• Released in response to ACTH, patterns of eating and activity, and stress
• Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins– Promotes rises in blood glucose, fatty acids, and
amino acids
• "Saves" glucose for brain• Enhances vasoconstriction rise in blood
pressure to quickly distribute nutrients to cells
Homeostatic Imbalances of Glucocorticoids
• Hypersecretion—Cushing's syndrome/disease– Depresses cartilage and bone formation– Inhibits inflammation– Depresses immune system– Disrupts cardiovascular, neural, and
gastrointestinal function
• Hyposecretion—Addison's disease– Also involves deficits in mineralocorticoids
• Decrease in glucose and Na+ levels• Weight loss, severe dehydration, and hypotension
Figure 16.16 The effects of excess glucocorticoid.
Patient before onset. Same patient with Cushing’s syndrome. The white arrow shows the characteristic “buffalo hump” of fat on the upper back.
Gonadocorticoids (Sex Hormones)
• Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens
• May contribute to– Onset of puberty– Appearance of secondary sex characteristics– Sex drive in women – Estrogens in postmenopausal women
Gonadocorticoids
• Hypersecretion– Adrenogenital syndrome (masculinization)– Not noticeable in adult males– Females and prepubertal males
• Boys – reproductive organs mature; secondary sex characteristics emerge early
• Females – beard, masculine pattern of body hair; clitoris resembles small penis
Adrenal Medulla
• Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%)
• Effects– Vasoconstriction– Increased heart rate– Increased blood glucose levels– Blood diverted to brain, heart, and skeletal
muscle
Adrenal Medulla
• Responses brief
• Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart
• Norepinephrine influences peripheral vasoconstriction and blood pressure
Adrenal Medulla
• Hypersecretion– Hyperglycemia, increased metabolic rate,
rapid heartbeat and palpitations, hypertension, intense nervousness, sweating
• Hyposecretion– Not problematic– Adrenal catecholamines not essential to life
Figure 16.17 Stress and the adrenal gland.
Short-term stress Prolonged stress
Nerve impulses
Spinal cord
Preganglionicsympatheticfibers
Adrenal medulla(secretes amino acid–based hormones)
Catecholamines(epinephrine andnorepinephrine)
Short-term stress response
Stress
Hypothalamus
Corticotropic cells of anterior pituitary
To target in blood
CRH (corticotropin-releasing hormone)
Adrenal cortex(secretes steroidhormones)
Mineralocorticoids Glucocorticoids
ACTH
• Heart rate increasesLong-term stress response
• Kidneys retain sodium and water
• Proteins and fats converted to glucose or broken down for energy• Blood glucose increases
• Blood pressure increases• Bronchioles dilate• Liver converts glycogen to glucose and releases glucose to blood• Blood flow changes, reducing digestive system activity and urine output• Metabolic rate increases
• Blood volume and blood pressure rise • Immune system
supressed
Pineal Gland
• Small gland hanging from roof of third ventricle • Pinealocytes secrete melatonin, derived from
serotonin• Melatonin may affect
– Timing of sexual maturation and puberty– Day/night cycles– Physiological processes that show rhythmic variations
(body temperature, sleep, appetite)– Production of antioxidant and detoxification molecules
in cells
‘Brain Sand’
Pancreas
• Triangular gland partially behind stomach
• Has both exocrine and endocrine cells– Acinar cells (exocrine) produce enzyme-rich
juice for digestion– Pancreatic islets (islets of Langerhans)
contain endocrine cells• Alpha () cells produce glucagon (hyperglycemic
hormone)• Beta () cells produce insulin (hypoglycemic
hormone)
Figure 16.18 Photomicrograph of differentially stained pancreatic tissue.
Pancreatic islet
• (Glucagon- producing) cells
• (Insulin- producing) cells
Pancreatic acinarcells (exocrine)
Glucagon
• Major target—liver
• Causes increased blood glucose levels
• Effects– Glycogenolysis—breakdown of glycogen to
glucose– Gluconeogenesis—synthesis of glucose
from lactic acid and noncarbohydrates– Release of glucose to blood
Insulin
• Effects of insulin– Lowers blood glucose levels– Enhances membrane transport of glucose into
fat and muscle cells– Inhibits glycogenolysis and gluconeogenesis– Participates in neuronal development and
learning and memory
• Not needed for glucose uptake in liver, kidney or brain
Insulin Action on Cells
• Activates tyrosine kinase enzyme receptor
• Cascade increased glucose uptake
• Triggers enzymes to– Catalyze oxidation of glucose for ATP
production – first priority– Polymerize glucose to form glycogen– Convert glucose to fat (particularly in adipose
tissue)
Factors That Influence Insulin Release
• Elevated blood glucose levels – primary stimulus• Rising blood levels of amino acids and fatty
acids• Release of acetylcholine by parasympathetic
nerve fibers• Hormones glucagon, epinephrine, growth
hormone, thyroxine, glucocorticoids• Somatostatin; sympathetic nervous system
Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels.Stimulates glucoseuptake by cells
Insulin
Stimulatesglycogenformationw
Pancreas
Tissue cells
Glucose Glycogen
LiverBloodglucosefalls tonormalrange.
IMBALANCEStimulus Bloodglucose level BALANCE: Normal blood glucose level (about 90 mg/100 ml)
Pancreas
IMBALANCE
Glucose Glycogen
Liver Stimulatesglycogenbreakdown
Bloodglucoserises tonormalrange.
Stimulus Bloodglucose level
Glucagon
Homeostatic Imbalances of Insulin
• Diabetes mellitus (DM)– Due to hyposecretion (type 1) or hypoactivity (type 2)
of insulin– Blood glucose levels remain high nausea higher
blood glucose levels (fight or flight response)– Glycosuria – glucose spilled into urine– Fats used for cellular fuel lipidemia; if severe
ketones (ketone bodies) from fatty acid metabolism ketonuria and ketoacidosis
– Untreated ketoacidosis hyperpnea; disrupted heart activity and O2 transport; depression of nervous system coma and death possible
Diabetes Mellitus: Signs
• Three cardinal signs of DM– Polyuria—huge urine output
• Glucose acts as osmotic diuretic
– Polydipsia—excessive thirst• From water loss due to polyuria
– Polyphagia—excessive hunger and food consumption
• Cells cannot take up glucose; are "starving"
Homeostatic Imbalances of Insulin
• Hyperinsulinism:– Excessive insulin secretion
– Causes hypoglycemia• Low blood glucose levels• Anxiety, nervousness, disorientation,
unconsciousness, even death
– Treated by sugar ingestion
Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus)
Ovaries and Placenta
• Gonads produce steroid sex hormones– Same as those of adrenal cortex
• Ovaries produce estrogens and progesterone– Estrogen
• Maturation of reproductive organs• Appearance of secondary sexual characteristics • With progesterone, causes breast development and cyclic
changes in uterine mucosa
• Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)
Testes
• Testes produce testosterone – Initiates maturation of male reproductive
organs– Causes appearance of male secondary
sexual characteristics and sex drive– Necessary for normal sperm production– Maintains reproductive organs in functional
state
Other Hormone-producing Structures
• Adipose tissue– Leptin – appetite control; stimulates
increased energy expenditure– Resistin – insulin antagonist– Adiponectin – enhances sensitivity to insulin
Other Hormone-producing Structures
• Enteroendocrine cells of gastrointestinal tract– Gastrin stimulates release of HCl– Secretin stimulates liver and pancreas– Cholecystokinin stimulates pancreas,
gallbladder, and hepatopancreatic sphincter– Serotonin acts as paracrine
Other Hormone-producing Structures
• Heart– Atrial natriuretic peptide (ANP) decreases
blood Na+ concentration, therefore blood pressure and blood volume
• Kidneys– Erythropoietin signals production of red
blood cells– Renin initiates the renin-angiotensin-
aldosterone mechanism
Other Hormone-producing Structures
• Skeleton (osteoblasts)– Osteocalcin
• Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat
• Activated by insulin• Low levels of osteocalcin in type 2 diabetes –
perhaps increasing levels may be new treatment
• Skin– Cholecalciferol, precursor of vitamin D
• Thymus– Large in infants and children; shrinks as age– Thymulin, thymopoietins, and thymosins
• May be involved in normal development of T lymphocytes in immune response
• Classified as hormones; act as paracrines
Other Hormone-producing Structures
Developmental Aspects
• Hormone-producing glands arise from all three germ layers
• Most endocrine organs operate well until old age• Exposure to pesticides, industrial chemicals,
arsenic, dioxin, and soil and water pollutants disrupts hormone function
• Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants
• Interference with glucocorticoids may help explain high cancer rates in certain areas
Developmental Aspects
• Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur
• Testosterone also diminishes with age, but effect is not usually seen until very old age
Developmental Aspects
• GH levels decline with age - accounts for muscle atrophy with age
• TH declines with age, contributing to lower basal metabolic rates
• PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH