Saladin 5e Extended Outline · Web view2020. 9. 1. · a. Thyroid follicles are filled with a protein-rich colloid and lined with a simple cuboidal epithelium of follicular cells

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Saladin A&P, 8e Extended Chapter Outline

Chapter 17 The Endocrine System

I. Overview of the Endocrine System (pp. 627–630)

A. The body has four principal avenues of communication from cell to cell. (p. 627)

1. Gap junctions join single-unit smooth muscle, cardiac muscle, epithelial, and other

cells, allowing passage of nutrients, electrolytes, and signaling molecules via the

cytoplasm. (Fig. 5.28)

2. Neurotransmitters are released by neurons, diffuse across the synaptic cleft, and bind to

receptors.

3. Paracrines are secreted by one cell, diffuse to nearby cells of the same tissue, and

stimulate them; they are sometimes called local hormones.

4. Hormones, in the strict sense, are chemical messengers transported by the bloodstream

that stimulate physiological responses of cells of another tissue or organ.

B. This chapter deals with hormones and some paracrine secretions. The glands, tissues, and cells

that secrete hormones are the endocrine system. (p. 627)

1. The study of this system and the diagnosis and treatment of its disorders is called

endocrinology.

2. The most familiar hormone sources are the endocrine glands, such as the

pituitary, thyroid, and adrenal glands, etc. (Fig. 17.1)

3. Hormones are also secreted by organs and tissues not usually thought of as glands,

such as the brain, heart, small intestine, bones, and adipose tissue.

C. The classical distinction between endocrine and exocrine glands has been the absence or

presence of ducts. (pp. 627–629)

1. Most exocrine glands secrete their products by way of a duct onto an epithelial surface.

(Fig. 5.30)

2. Endocrine glands, in contrast, are ductless and release their secretions into the

bloodstream. Hormones were originally called the body’s “internal secretions,” from

which the glands get their name.

3. Exocrine secretions have extracellular effects, whereas endocrine secretions have

intracellular effects, altering cell metabolism.

4. Endocrine glands have a high density of blood capillaries, which are of a highly

permeable type called fenestrated capillaries, which have patches of large pores in their

walls.

Saladin Outline Ch.17

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5. Some glands and secretory cells are not easily classified as one or the other type. For

example, liver cells behave as exocrine cells when they secrete bile, but they also secrete

hormones into the blood, along with other factors.

D. The nervous and endocrine systems complement each other rather than duplicate each other’s

functions. (pp. 629–630) (Table 17.1)

1. They differ in the speed of communication. The nervous system responds within

milliseconds, whereas it takes from several seconds to days for a hormone to act.

a. When a stimulus ends, the nervous system stops responding almost

immediately, whereas hormonal effects may last for several days or longer.

b. Under long-term stimulation, most neurons adapt and response declines, but

endocrine system response is more persistent.

2. Another difference is that an efferent nerve fiber innervates only one organ and a

limited number of cells, so its effects are targeted, while in contrast, hormones circulate

throughout the body and have more widespread effects.

3. In terms of similarities, several chemicals function both as neurotransmitters and as

hormones, including norepinephrine, dopamine, and antidiuretic hormone.

a. For example, dopamine is considered a hormone when it is secreted by an

endocrine cell but a neurotransmitter when it is secreted by a nerve cell.

4. Some hormones and neurotransmitters produce identical effects on the same targets,

such as glucagon and norepinephrine acting on the liver cells.

5. The nervous and endocrine systems regulate each other. That is, neurons often trigger

hormone secretion, and hormones often stimulate or inhibit neurons.

6. Neuroendocrine cells act like neurons, but like endocrine cells, they release their

secretions into the bloodstream.

7. Both neurotransmitters and hormones depend on receptors on the receiving cells. The

specificity of target organs or cells allows selective responses to circulating hormones.

(Fig. 17.2)

E. In terms of nomenclature, many hormones are denoted by standard abbreviations. (p. 633)

(Table 17.2)

II. The Hypothalamus and Pituitary Gland (pp. 630–637)

A. The pituitary gland and hypothalamus have a more wide-ranging influence than any other part

of the endocrine system. (p. 630)

B. Anatomically, the pituitary is suspended from the floor of the hypothalamus. (pp. 630–633)

1. The hypothalamus is shaped like a flattened funnel and forms the floor and walls of the

third ventricle of the brain. (Figs. 14.2, 14.12b)

2. The pituitary gland (hypophysis) is connected to the hypothalamus by a stalk

(infundibulum) and housed in a depression of the sphenoid bone, the sella turcica.


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a. The gland is roughly the size and shape of a kidney bean, usually about

1.3 cm wide; it grows 50% larger in pregnancy.

b. It is composed of two structures, the anterior and posterior pituitary, which

have independent origins and separate functions. (Fig. 17.3)

i. The anterior pituitary arises from a hypophyseal pouch that grows

upward from the embryonic pharynx.

ii. The posterior pituitary arises as a bud growing downward from the

brain.

c. The anterior pituitary (anterior lobe or adenohypophysis) constitutes about

three-quarters of the pituitary. (Figs. 17.4a, 17.5a)

i. It has no nervous connection to the hypothalamus but is linked to it

by the hypophyseal portal system. (Fig. 17.4b)

ii. This portal system consists of a network of primary capillaries in the

hypothalamus, a group of veins called portal venules that travel down

the stalk, and a complex of secondary capillaries in the anterior

pituitary.

iii. The hypothalamus controls the anterior pituitary by secreting

hormones into the primary capillaries.

d. The posterior pituitary (posterior lobe or neurohypophysis) constitutes the

posterior one-quarter of the pituitary.

e. The neurohypophysis is nervous tissue and not a true gland. (Fig. 17.5b)

i. The nerve fibers arise from certain cell bodies in the hypothalamus

and pass down the stalk as the hypothalamo-hypophyseal tract to end in

the posterior lobe. (Fig. 17.4a)

ii. The hypothalamic neurons synthesize hormones and transport them

down the nerve fibers by axoplasmic flow to the posterior pituitary,

where they are stored until a nerve signal from the same axons triggers

their release into the blood.

C. Eight hormones are produced in the hypothalamus: six regulate the anterior pituitary and

two are stored in the posterior pituitary and released on demand. (pp. 633–634) (Fig. 17.4)

1. Among the first six, those that stimulate pituitary cells to secrete hormones of their

own are called releasing hormones, while those that suppress pituitary secretion are

called inhibiting hormones. (Table 17.3)

a. The releasing or inhibiting effect is identified in the names of the hormones.

For example, somastatin inhibits growth hormone, which is known as

somatotropin.


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2. The other two hypothalamic hormones are oxytocin (OT) and antidiuretic hormone

(ADH).

a. OT comes mainly from neurons in the right and left paraventricular nuclei of

the hypothalamus, named because they lie in the walls of the third ventricle.

b. ADH comes mainly from the supraoptic nuclei, named for their location just

above the optic chiasm.

c. They are stored and released by the posterior pituitary and so are considered

posterior lobe hormones even though not synthesized there.

D. The six anterior pituitary hormones are summarized as follows. (pp. 633–634) (Table 17.4)

1. Follicle-stimulating hormone (FSH) is secreted by pituitary cells called gonadotropes.

a. In the ovaries, FSH stimulates secretion of ovarian sex hormones and the

development of follicles.

b. In the testes it stimulates sperm production.

2. Luteinizing hormone (LH) is also secreted by the gonadotropes; FSH and LH are

collectively termed gonadotropins.

a. LH stimulates ovulation in females; after ovulation the follicle becomes a

yellowish body termed the corpus luteum, from which LH gets its name.

b. LH also stimulates the corpus luteum to secrete progesterone.

c. In males, LH stimulates the testes to secrete testosterone.

3. Thyroid-stimulating hormone (TSH), or thyrotropin, is secreted by cells called

thyrotropes.

a. It stimulates growth of the thyroid gland and the secretion of thyroid

hormone.

4. Adrenocorticotropic hormone (ACTH), or corticotropin, is secreted by cells called

corticotropes.

a. Its target organ is the adrenal cortex.

b. It stimulates the cortex to release glucocorticoids (especially cortisol), which

are involved in the stress response.

5. Prolactin (PRL) is secreted by cells called lactotropes (mammotropes).

a. PRL secretion increases during pregnancy but has no effect until after a

woman gives birth, when it stimulates the mammary glands to synthesize milk.

6. Growth hormone (GH), or somatotropin, is secreted by somatotropes, the most

numerous cells of the anterior pituitary.

a. The pituitary produces at least a thousand times as much GH as any other

hormone.

b. GH stimulates mitosis and cellular differentiation to promote tissue growth.


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7. The anterior pituitary is thus involved in a chain of events linked by hormones. This

chain begins in the hypothalamus and ends with the binding of hormones from the

anterior pituitary to target organs. (Fig. 17.6)

E. The two posterior lobe hormones are ADH and OT, which are synthesized in the

hypothalamus and then transported to the posterior pituitary for storage. (pp. 634–635)

1. Antidiuretic hormone (ADH) increases water retention by the kidneys, reduces urine

volume, and helps prevent dehydration.

a. ADH also functions as a neurotransmitter and is usually called arginine

vasopressin (AVP) in neuroscience literature. This name refers to its ability to

cause vasoconstriction, but the concentration required is unnaturally high, so it

is of doubtful significance except in pathological states.

2. Oxytocin (OT) has a variety of reproductive functions ranging from intercourse to birth

to breast-feeding.

a. OT surges during sexual arousal and orgasm.

b. It also functions in feelings of sexual satisfaction and emotional bonding

between partners.

c. In childbirth, it stimulates labor contractions.

d. In lactating mothers, it stimulates the flow of milk from mammary gland to

the nipple.

e. It may also play a role in bonding between mother and infant.

F. The control of pituitary hormone secretion, in terms of type, timing, and amount, is regulated

by the hypothalamus, other brain centers, and feedback from target organs. (pp. 635–636)

1. Hypothalamic control enables the brain to monitor conditions within and outside the

body and to stimulate or inhibit the release of anterior lobe hormones appropriately.

a. In times of stress, the hypothalamus triggers ACTH secretion, which leads to

secretion of cortisol and mobilization of materials for tissue repair.

b. During pregnancy, the hypothalamus induces prolactin secretion so a woman

will be prepared to lactate after giving birth.

2. The posterior pituitary is controlled by neuroendocrine reflexes—the release of

hormones in response to nerve signals.

a. Dehydration raises the osmolarity of the blood, which is detected by

hypothalamic neurons called osmoreceptors. They trigger the release of ADH,

which promotes water conservation.

b. Excessive blood pressure stimulates stretch receptors in the heart and certain

arteries, and via another neuroendocrine reflex, ADH release is inhibited,

increasing urine output.


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c. The suckling of an infant stimulates nerve endings in the nipple, sending

sensory signals to spinal cord, brainstem, and hypothalamus, and finally to the

posterior pituitary, causing the release of OT, which stimulates the release of

milk.

d. Neuroendocrine reflexes can also involve higher brain centers, as when

hearing a baby’s cry stimulates a lactating woman to release milk.

3. Feedback from target organs also regulates the pituitary and hypothalamus through

feedback loops.

a. Most often, this regulation occurs by negative feedback inhibition, in which

the hormone itself inhibits further secretion by binding to the pituitary or

hypothalamus. (Fig. 17.7)

b. In the pituitary–thyroid system, the feedback inhibition is as follows:

i. The hypothalamus secretes thyrotropin-releasing hormone (TRH).

ii. TRH stimulates the anterior pituitary to secrete TSH.

iii. TSH stimulates the thyroid to secrete TH.

iv. TH stimulates the metabolism of most cells throughout the body.

v. TH also inhibits the release of TSH by the pituitary.

vi. To a lesser extent, TH inhibits the release of TRH by the

hypothalamus.

c. Steps five and six are the negative feedback inhibition steps, and they ensure

that thyroid hormone secretion oscillates around a set point.

d. Feedback is not always inhibitory. OT triggers a positive feedback cycle

during labor that continues until the infant is born. (Fig. 1.8)

G. Growth hormone is unlike other pituitary hormones in that it is not targeted to just one or a few

organs but has widespread effects on the body. (pp. 636–637)

1. GH directly stimulates tissues, especially cartilage, bone, muscle, and fat. It also

induces the liver and other tissues to produce insulin-like growth factors (IGF-I and IGF-

II), also known as somatomedins, which then stimulate target cells. (Fig. 17.6)

a. One effect of IGF is to prolong the action of GH. The half-life of GH is only 6

to 20 minutes, whereas that of IGFs is about 20 hours.

2. The mechanisms of GH–IGF action include the following:

a. Protein synthesis.

i. Within minutes of its secretion, GH boosts the translation of existing

mRNA, and within a few hours it also boosts DNA transcription.

ii. It also enhances amino acid transport into cells.

iii. GH also suppresses protein catabolism.

b. Lipid metabolism.


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i. GH stimulates adipocytes to catabolize fat and release fatty acids and

glycerol.

ii. By providing these fuels, GH makes it unnecessary for cells to

consume their proteins, which is called the protein-sparing effect.

c. Carbohydrate metabolism.

i. GH also has a glucose-sparing effect. Its role in mobilizing fatty acids

reduces the dependence of cells on glucose so they will not compete

with the brain.

ii. GH also stimulates glucose synthesis by the liver.

d. Electrolyte balance.

i. GH promotes Na+, K+, and Cl– retention by the kidneys.

ii. GH enhances Ca2+ absorption by the small intestine.

3. The most conspicuous effects of GH are on bone, cartilage, and muscle growth,

especially during childhood and adolescence.

a. IGF-I accelerates bone growth at the epiphyseal plates and stimulates

multiplication of chondrocytes and osteogenic cells.

b. It increases protein deposition in the cartilage and bone matrix.

c. In adulthood, it stimulates osteoblast activity and the appositional growth of

bone, influencing bone thickening and remodeling.

4. GH secretion fluctuates over the course of a day.

a. The GH level in blood plasma rises to 20 nanograms per milliliter (ng/mL) or

higher during the first 2 hours of deep sleep, and may reach 30 ng/mL in

response to vigorous exercise.

b. Trauma, hypoglycemia, and other conditions also stimulate GH secretion.

c. Small peaks occur after high-protein meals, but a high-carbohydrate meal

tends to suppress GH secretion.

5. GH levels decline gradually with age.

a. The average concentration is 6 ng/mL in adolescence, and one-quarter of that

in very old age.

b. At age 30, the average adult body is 10% bone, 30% muscle, and 20% fat. At

age 75, the average is 8% bone, 15% muscle, and 40% fat.

III. Other Endocrine Glands (pp. 637–647)

A. The pineal gland is attached to the roof of the third ventricle, beneath the posterior end of the

corpus callosum. (pp. 637-638) (Figs. 17.1 and 14.2)

1. Its name alludes to a shape resembling a pine cone.

2. A child’s pineal gland is about 8 mm long and 5 mm wide, but after age 7 it regresses,

a process called involution.


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3. Pineal secretion peaks between the ages of 1 and 5 years and declines 75% by the end

of puberty.

4. The pineal gland’s function is somewhat mysterious; it may plan a role in establishing

circadian rhythms of physiological function.

a. During the night it synthesizes melatonin, a monoamine, from serotonin.

i. Melatonin has been implicated in some human mood disorders,

although the evidence is inconclusive.

ii. Its secretion fluctuates seasonally with changes in day length, and in

animals that have seasonal breeding cycles.

Insight 17.1 Melatonin, SAD, and PMS

iii. Melatonin may suppress gonadotropin secretion, since removal of

the pineal gland from animals causes premature sexual maturation.

b. The pineal gland may regulate the timing of puberty in humans, but this has

not been conclusively demonstrated.

c. Pineal tumors cause premature puberty in boys, but such tumors also damage

the hypothalamus, so it is inconclusive as to whether the effect is due to pineal

damage.

B. The thymus is a bilobed gland in the mediastinum superior to the heart, behind the sternal

manubrium. It plays a role in the endocrine, lymphatic, and immune systems. (p. 638)

1. In the fetus and infant, it is relatively large, sometimes protruding between the lungs

from near the diaphragm and extending upward to the base of the neck. (Fig. 17.8a)

2. It continues to grow until 5 or 6 years of age. In adults, it weighs about 20 g up to age

60, but becomes less glandular, remaining as a small fibrous and fatty remnant in the

elderly. (Fig. 17.8b)

3. The thymus is a site of maturation for T cells that are critically important for immune

defense.

4. It secretes thymopoietin, thymosin, and thymulin, which stimulate the development of

other lymphatic organs and regulate the development and activity of T cells.

C. The thyroid gland weighs about 25 g and is the largest adult gland to have a purely endocrine

function. It is composed of two lobes that lie adjacent to the trachea immediately below the larynx.

(pp. 638–639)

1. It is named for the shieldlike thyroid cartilage of the larynx.

2. Near the inferior end, the two lobes are usually joined by a narrow anterior bridge of

tissue, the isthmus. (Figs. 17.8 and 17.9a)

3. It receives one of the highest rates of blood flow per gram of tissue and is dark reddish

brown in color. (Fig. 17.9a)

4. Histologically, it is composed mostly of sacs called thyroid follicles. (Fig. 17.9b)


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a. Thyroid follicles are filled with a protein-rich colloid and lined with a simple

cuboidal epithelium of follicular cells.

b. These cells secrete thyroxine (T4, tetraiodothyronine) and triiodothryonine

(T3); they are collectively termed thyroid hormone (TH).

i. An average adult thyroid secretes 80 μg of TH daily, of which 90%

is T4.

c. Thyroid hormone is secreted in response to TSH from the pituitary, and the

primary effect of TH is to increase the body’s metabolic rate.

d. TH raises oxygen consumption and has a calorigenic effect—it increases heat

production.

i. To ensure an adequate blood and oxygen supply to meet the increased

metabolic need, it raises the respiratory rate, heart rate, and strength of

the heartbeat. It stimulates the appetite and accelerates the breakdown

of carbohydrates, fats, and proteins for fuel.

ii. It also promotes alertness and quicker reflexes; secretion of GH;

growth of bones, skin, hair, nails, and teeth; and development of the

fetal nervous system.

5. The thyroid gland also contains nests of C (clear) cells, or parafollicular cells, between

the follicles.

a. These cells secrete calcitonin in response to rising levels of blood calcium,

which stimulates osteoblast activity and calcium deposition while antagonizing

the action of parathyroid hormone.

b. It is important mainly in children, having relatively little effect in adults.

D. The parathyroid glands are ovoid glands about 3 to 8 mm long and 2 to 5 mm wide. Four of

them are found partially embedded in the posterior surface of the thyroid, separated by a thin

fibrous capsule. (p. 639) (Fig. 17.10)

1. Sometimes they occur in other locations ranging from as high as the hyoid bone to as

low as the aortic arch; about 5% of people have more than four.

2. They secrete parathyroid hormone (PTH) in response to low blood calcium levels.

E. The adrenal (suprarenal) glands sit like caps on the superior surface of each kidney.

(pp. 639–642) (Fig. 17.11)

1. Like the kidneys, they are retroperitoneal.

2. The adult adrenal gland measures about 5 cm vertically, 3 cm wide, and 1 cm anterior

to posterior. It weighs about 8 to 10 g in the newborn, but by the age of 2 years following

involution of its outer layer, it is reduced to 4 to 5 g and remains this weight in adults.


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3. The gland forms by the merger of two fetal glands with different origins and functions:

the gray to dark red adrenal medulla is 10% to 20% of the gland, and the yellowish

adrenal cortex is 80% to 90% of the gland.

4. The adrenal medulla has a dual nature, acting as both an endocrine gland and as a

ganglion of the sympathetic nervous system.

a. Sympathetic preganglionic nerve fibers extend through the cortex to reach

chromaffin cells in the medulla.

i. These cells have no dendrites or axon, and they release their products

into the bloodstream; they are considered neuroendocrine cells.

b. Upon stimulation by nerve fibers—usually under conditions of fear, pain, or

other stress—the chromaffin cells release a mixture of catecholamines.

i. About three- quarters of the mixture is epinephrine, one-quarter is

norepinephrine, and a trace is dopamine.

ii. These increase alertness and prepare the body for physical activity.

iii. They mobilize high energy fuels and boost glucose levels by

glycogenolysis and gluconeogenesis.

c. Epinephrine has a glucose-sparing effect in that it inhibits the secretion of

insulin, so that muscles and other insulin-dependent organs absorb and consume

less glucose.

d. The adrenal catecholamines also raise the heart rate and blood pressure,

stimulate circulation, increase pulmonary airflow, and raise the metabolic rate.

e. The catecholamines inhibit functions such as digestion and urine production.

5. The adrenal cortex, which surrounds the medulla, produces more than 25 steroid

hormones known as the corticosteroids or corticoids.

a. Only five of these are produced in physiologically significant amounts or

active forms.

b. These five fall into three categories: mineralocorticoids, which regulate the

body’s electrolyte balance; glucocorticoids, which regulate the metabolism of

glucose and other organic fuels; and sex steroids, which have various

developmental and reproductive functions.

c. The adrenal cortex has three layers of tissue, which differ in their histology

and hormones produced. (Fig. 17.11b)

i. The zona glomerulosa is a thin layer located just beneath the capsule

at the gland surface. Glomerulosa refers to the round clusters of cells in

this zone. The zona glomerulosa secretes mineralocorticoids.

ii. The zona fasciculata is a thick middle layer constituting about three-

quarters of the adrenal cortex. The cells in this zone are arranged in


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parallel cords (fascicles) separated by blood capillaries, perpendicular

to the gland surface. The cells are called spongiocytes because of the

abundance of cytoplasmic lipid droplets. The zona fasciculata secretes

glucocorticoids and androgens.

iii. The zona reticularis is the narrow, innermost layer, adjacent to the

renal medulla. Cells of this zone form a branching network for which

this layer is named. It also secretes glucocorticoids and androgens.

6. Aldosterone is the most significant mineralocorticoid, and is produced only by the

zona glomerulosa.

a. It is part of the renin–aldosterone–angiotensin hormone system that stimulates

the kidneys to retain sodium and excrete potassium. (Fig. 23.15)

b. Because water is retained along with sodium, aldosterone helps to maintain

blood volume and pressure.

7. Cortisol (hydrocortisone) is the most potent glucocorticoid; the adrenals also secrete a

weaker one called corticosterone.

a. Glucocorticoids stimulate fat and protein catabolism, gluconeogenesis, and

the release of fatty acids and glucose into the blood.

b. These hormones also have an anti-inflammatory effect and are used to relieve

swelling and other signs of inflammation.

c. Excessive secretion or medical use suppresses the immune system.

8. Androgens are the primary adrenal sex steroids, but the adrenals also secrete small

amounts of estrogen.

a. The major androgen is dehydroepiandrosterone (DHEA). It has little

biological activity, but most tissues convert it to the more potent forms,

testosterone and dihydrotestosterone.

b. DHEA is produced in tremendous quantities by the large adrenal glands of the

male fetus and plays an important role in prenatal development of the

reproductive tract.

c. In both sexes, androgens are responsible for development of secondary sexual

characteristics in puberty.

d. In men, the large amount of androgen produced by the testes greatly

overshadows that produced by the adrenals, but in women, the adrenal glands

provide about 50% of the androgen requirement.

9. The main adrenal estrogen is estradiol. This is of minor importance to women during

reproductive years, but it is the main source of estrogen after menopause.

10. The medulla and cortex are not as functionally independent as once thought; each of

them stimulates the other.


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a. Without stimulation by cortisol, the adrenal medulla atrophies significantly.

b. Conversely, some chromaffin cells extend into the cortex, and when stress

activates the sympathetic nervous system, these cells stimulate the cortex to

secrete corticosterone.

F. The pancreas is an elongated, spongy, primarily exocrine gland located below and behind the

stomach. It secretes digestive enzymes—but scattered throughout its exocrine tissue are 1 to 2

million endocrine cell clusters called pancreatic islets (islets of Langerhans). (pp. 642–643)

(Fig. 17.12)

1. Although they are less than 2% of the pancreatic tissue, the islets secrete hormones of

vital importance in regulating glycemia, the blood glucose concentration.

2. An islet measures about 75 × 175 µm and contains from a few to 3,000 cells, of which

about 20% are alpha cells, 70% are beta cells, 5% are delta cells, and about 5% are called

PP and G cells.

a. Alpha (α) cells, or A cells, secrete glucagon between meals when the blood

glucose concentration is falling.

i. In the liver, glucagons stimulates gluconeogenesis, glycogenolysis,

and the release of glucose into the circulation.

ii. In adipose tissue, it stimulates fat catabolism and the release of free

fatty acids.

iii. Glucagon is also secreted in response to rising amino acid levels

after a high-protein meal. It promotes amino acid absorption, providing

cells with the raw material for gluconeogenesis.

b. Beta (β) cells, or B cells, secrete insulin during and immediately following a

meal, when blood nutrient levels are rising. Insulin’s main targets are the liver,

skeletal muscle, and adipose tissue.

i. Insulin stimulates cells to absorb these nutrients and store or

metabolize them.

ii. It promotes the synthesis of glycogen, fat, and protein, and thus

promotes the storage of excess nutrients.

iii. It also antagonizes the effects of glucagon.

iv. The brain, liver, kidneys, and red blood cells absorb and use glucose

without insulin, but insulin does promote glycogen synthesis in the

liver.

v. Insulin insufficiency or inaction is the cause of diabetes mellitus.

c. Delta (δ) cells, or D cells, secrete somatostatin (growth hormone–inhibiting

hormone) concurrently with the release of insulin by the beta cells.

i. Somatostatin inhibits the secretion of stomach acid.


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3. Any hormone that raises blood glucose level is called a hyperglycemic hormone.

Insulin is a hypoglycemic hormone because it lowers blood glucose levels.

G. The gonads (ovaries and testes) are like the pancreas in that they are both endocrine and

exocrine. (p. 643)

1. Their exocrine products are whole cells—eggs and sperm—and thus they are

sometimes called cytogenic glands.

2. Their endocrine products are the gonadal hormones, most of which are steroids.

3. The ovaries secrete chiefly estradiol, progesterone, and inhibin.

4. Each egg develops in its own follicle, which is lined by a wall of granulosa cells and

surrounded by a capsule, the theca. (Fig. 17.13a)

a. Theca cells synthesize androstenedione, and granulosa cells convert this to

estradiol and lesser amounts of estriol and estrone.

b. In the middle of the ovarian cycle, a mature follicle ruptures and releases the

egg.

c. The remains of the follicle become the corpus luteum, which secretes

progesterone for the next 12 days in a typical cycle, or several weeks in the

event of pregnancy.

d. Estradiol and progesterone contribute to the development of the reproductive

system and female physique, as well as promote bone growth, regulate the

menstrual cycle, sustain pregnancy, and prepare the mammary glands for

lactation.

i. Inhibin, which is also secreted by the follicle and corpus luteum,

suppresses the secretion of FSH by the anterior pituitary.

e. A testis consists mainly of seminiferous tubules that produce sperm.

f. Its endocrine secretions are testosterone, lesser amounts of weaker androgens

and estrogens, and inhibin.

i. Inhibin comes from sustentacular (Sertoli) cells that form the walls of

the seminiferous tubules.

ii. By limiting FSH secretion, inhibin regulates the rate of sperm

production.

g. Nestled between the tubules are clusters of interstitial cells (cells of Leydig),

the source of the gonadal steroids. (Fig. 17.13b)

h. Testosterone stimulates development of the male reproductive system in the

fetus and adolescent, the development of the male physique in adolescence, and

the sex drive.

H. Several other tissues and organs secrete hormones or hormone precursors. (pp. 643–647)


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1. The skin. Keratinocytes of the epidermis convert a cholesterol-like steroid into

cholecalciferol using UV radiation from the sun.

a. The liver and kidneys convert cholecalciferol to a calcium-regulating

hormone, calcitriol.

2. The liver. The liver is involved in production of at least five hormones.

a. It converts cholecalciferol into calcidiol, the next step in calcitriol synthesis.

b. It secretes angiotensinogen, a protein that is converted by kidneys, lungs, and

other organs into the hormone angiotensin II, which is a regulator of blood

pressure.

c. The liver secretes about 15% of the body’s erythropoietin (EPO), which

stimulates the production of red blood cells by the red bone marrow.

d. It secretes hepcidin, a recently discovered hormone involved in iron

homeostasis.

i. Hepcidin promotes intestinal absorption of dietary iron and

mobilization of iron for hemoglobin synthesis and other uses.

e. The liver secretes insulin-like growth factor I (IGF-I), a hormone that

mediates the action of growth hormone.

3. The kidneys. The kidneys produce three hormones—calcitriol, angiotensin II, and

erythropoietin.

a. They convert calcidiol into calcitriol (vitamin D3), which raises blood

concentration of calcium by promoting its intestinal absorption.

b. They secrete renin, an enzyme that converts angiotensinogen to angiotensin I.

i. As angiotensin I circulates, it is converted to angiotensin II by

angiotensin-coverting enzyme (ACE) in the linings of certain blood

capillaries. Angiotensin II constricts blood vessels and raises blood

pressure.

c. The kidneys secrete about 85% of the body’s erythropoietin.

4. The heart. Rising blood pressure stretches the heart wall and stimulates cardiac muscle

in the atria to secrete two similar natriuretic peptides.

a. These hormones increase sodium excretion and urine output and oppose the

action of angiotensin II.

5. The stomach and small intestine. These contain enteroendocrine cells, which secrete at

least 10 eneteric hormones that coordinate actions of the digestive system.

a. Cholecystokinin (CCK) is secreted when fats arrive and stimulates the

gallbladder to release bile.

b. Gastrin is secreted by cells in the stomach upon arrival of food and stimulates

hydrochloric acid secretion.


15

c. Ghrelin is secreted when the stomach is empty, producing the sensation of

hunger.

d. Peptide YY (PYY), secreted by cells of the small and large intestines, signals

satiety.

6. Adipose tissue. Fat cells secrete the hormone leptin, which has long-term effects on

appetite-regulating centers of the hypothalamus.

a. A low level of leptin (low body fat) increases appetite, whereas a high level of

leptin (high body fat) tends to decrease appetite.

b. Leptin also serves as a signal for the onset of puberty, which is delayed in

persons with abnormally low body fat.

7. Osseous tissue. Osteoblasts secrete the hormone osteocalcin, which increases the

number of pancreatic beta cells, pancreatic output of insulin, and the insulin sensitivity of

other body tissues.

a. Osteocalcin seems to inhibit fat deposition and the onset of type 2 diabetes

mellitus.

8. The placenta. This organ performs many functions during pregnancy, including fetal

nutrition and waste removal. It also secretes estrogen, progesterone, and other hormones

that regulate pregnancy and stimulate development of the fetus and mammary glands.

9. Endocrine organs and tissues other than the hypothalamus and pituitary are reviewed in

Table 17.5.

IV. Hormones and Their Actions (pp. 647–656)

A. Hormones fall into three chemical classes: steroids, monoamines, and peptides. (p. 647–648)

(Fig. 17.14) (Table 17.6)

1. Steroid hormones are derived from cholesterol.

a. They include the sex hormones produced by the testes and ovaries and

corticosteroids produced by the adrenal gland.

b. Calcitriol, the calcium-regulating hormone, is not a steroid but is derived from

one and has the same character and mode of action as the steroids.

2. Monoamines (biogenic amines) are made from amino acids and retain an amino group.

This class includes several neurotransmitters. (Fig. 12.21)

a. The monoamine hormones include dopamine, epinephrine, norepinephrine,

melatonin, and thyroid hormone.

b. Dopamine, epinephrine, and norepinephrine are called catecholamines.

3. Peptide hormones are chains of 3 to 200 or more amino acids.

a. Oxytocin and antidiuretic hormone, from the posterior pituitary, are very

similar oligopeptides of just nine amino acids.

b. Insulin is probably the best-known large peptide hormone.


16

c. Except for dopamine, the releasing and inhibiting hormones of the

hypothalamus are polypeptides.

d. Most hormones of the anterior pituitary are polypeptides or glycoproteins.

e. Most glycoprotein hormones have an identical alpha chain of 92 amino acids

and a variable beta chain.

B. All hormones are synthesized from either cholesterol or amino acids, with carbohydrate added

in the case of glycoproteins. (pp. 648–651)

1. Steroid hormones are synthesized from cholesterol and differ mainly in the functional

groups attached to the four-ringed steroid backbone. (Fig. 17.15)

a. Although estrogen and progesterone are thought of as “female” hormones and

testosterone as a “male” hormone, they are interrelated in synthesis and have

roles in both sexes.

2. Peptide hormones are synthesized in the same way as any other protein.

a. The gene is transcribed to form mRNA, and ribosomes translate the mRNA

and assemble amino acids in the right order to make the peptide.

b. Once assembled, the rough endoplasmic reticulum and Golgi complex may

modify the peptide to form the mature hormone.

c. Insulin begins as a single amino acid chain called proinsulin.

i. A middle portion, the connecting peptide, is removed to convert

proinsulin to insulin, now composed of two polypeptide chains

connected to each other by disulfide bridges. (Fig. 17.16)

3. Monoamines are also made from amino acids.

a. Melatonin is synthesized from the amino acid tryptophan, and the other

monoamines from the amino acid tyrosine.

b. Thyroid hormone is unusual in that each molecule is composed of two

tyrosines.

c. The synthesis, storage, and secretion of thyroid hormone (TH) take place as

follows: (Fig. 17.17)

i. Follicular cells absorb iodide ions (I–) from the blood plasma and

oxidize I– to a reactive form (I*).

ii. Meanwhile, the follicular cells synthesize thyroglobulin (Tg). Each

molecule of has 123 tyrosines among its amino acids, but only 4 to 8

are used to make thyroid hormone. The cells release thyroglobulin by

exocytosis into the lumen of the thyroid follicle.

iii. An enzyme at the cell surface adds iodine to some of the tyrosines.

Some tyrosines receive one iodide and become monoiodotyrosine

(MIT), while others receive two and become diiodotyrosine (DIT). Two


17

tyrosines can link to each other through their side groups. When an

MIT links with a DIT, they form a complex destined to become T3; if

two DITs link, they formT4. One tyrosine then breaks away from its Tg

but the hormone remains temporarily bound to Tg through its other

tyrosine. Tg is stored in the follicles until the thyroid gland receives a

signal to release it. (Figs. 17.17b and 17.9b)

iv. When the cells receive thyroid-stimulating hormone, they absorb Tg

by pinocytosis. A lysosomal enzyme hydrolyzes the peptide chain of

Tg, liberating TH.

v. TH is released into the blood and binds with transport proteins that

carry it to its target cells. The released hormone is about 10% T3 and

90% T4. (Fig. 17.17c)

C. Hormone transport through the blood, which is mostly water, is a simple matter for

monoamines and peptides, but the hydrophobic steroids and thyroid hormone must bind to

hydrophilic transport proteins. (p. 651)

1. Albumins and globulins synthesized by the liver act as transport proteins.

2. A hormone attached to a transport protein is called bound hormone, and one that is not

attached is an unbound or free hormone.

3. Only the unbound hormone can leave a blood capillary and get to a target cell.

(Fig. 17.18)

4. Unbound hormone can be broken down or removed from the blood in a few minutes,

whereas bound hormone may circulate for hours to weeks.

5. Thyroid hormone binds to three transport proteins: albumin, thyretin (an albumin-like

protein), and an alpha globulin named thyroxine-binding globulin (TBG).

a. TBG binds the greatest amount.

b. More than 99% of circulating TH is bound.

6. Steroid hormones bind to globulins such as transcortin, the transport protein for

cortisol.

7. Aldosterone is unusual in that it has no specific transport protein but binds weakly to

albumin and others. However, 85% remains unbound and thus it has a half-life of only 20

minutes.

D. Hormones stimulate only those cells that have receptors for them, and the receptors act like

switches to turn certain metabolic pathways on or off when the hormone binds to them.

(pp. 651–654)

1. Receptor–hormone interactions are similar to enzyme–substrate interactions. Unlike

enzymes, receptors do not chemically change their ligands; they do, however, exhibit

specificity and saturation.


18

a. Specificity means that a receptor for one hormone will not bind other

hormones.

b. Saturation is the condition in which all receptor molecules are occupied by

hormone molecules.

Insight 17.2 Hormone Receptors and Therapy

2. Steroid hormones and thyroid hormone enter the target cell nucleus and act directly on

the genes by activating or inhibiting transcription.

a. Steroid hormones are hydrophobic and diffuse easily through the plasma

membrane.

b. Most pass directly into the nucleus, but glucocorticoids bind to a receptor in

the cytosol, and the complex is then transported into the nucleus.

c. Estrogen and progesterone both act on cells of the uterine mucosa in a way

typical of steroids.

i. Estrogen activates a gene for the protein that functions as the

progesterone receptor.

ii. Progesterone binds to these receptors later, stimulating transcription

of the gene for a glycogen-synthesizing enzyme.

iii. The uterine cell then synthesizes and accumulates glycogen for the

nourishment of an embryo in the case of pregnancy.

iv. Progesterone has no effect on these cells unless estrogen has been

there earlier.

d. Thyroid hormone in the T4 form has little metabolic effect, but in the target

cell cytoplasm, an enzyme converts T4 to the more potent T3.

i. T3 enters the target cell nucleus and binds to receptors.

ii. One of the genes activated by T3 is for the enzyme Na+-K+ ATPase,

the sodium–potassium pump. One of the effects of this pump is to

generate heat.

iii. T3 also activates transcription of genes for a norepinephrine receptor

and a component of myosin, enhancing cell responsiveness to

sympathetic nervous system stimulation.

e. Steroid and thyroid hormones typically require several hours to days to show

an effect, due to the lag time for transcription, translation, and accumulation of

protein.

3. Peptides and catecholamines are hydrophilic and cannot penetrate into target cells, so

they bind to cell surface receptors linked to second-messenger systems. (Fig. 17.18a)

a. Glucagon binds to receptors on the surface of a liver cell, which activates a G

protein.


19

i. This G protein in turn activates adenylate cyclase to produce cAMP,

a second messenger.

ii. cAMP leads ultimately to the activation of enzymes that hydrolyze

glycogen. (Fig. 17.19)

b. Somatostatin inhibits cAMP synthesis.

c. Second messengers do not linger in the cell, but are quickly broken down. For

example, cAMP is broken down by phosphodiesterase.

d. Two other second-messenger systems begin with one of the phospholipids in

the plasma membrane. (Fig. 17.20)

i. When activated, the receptor activates a G protein linked to a nearby

enzyme, phospholipase.

ii. Phospholipase splits a membrane phospholipid into two fragments—

inositol triphosphate (IP3) and diacylglycerol (DAG).

e. DAG activates a protein kinase (PK), in the same manner as cAMP does,

which phosphorylates several other enzymes.

f. IP3 opens Ca2+ channels in the plasma membrane or in the endoplasmic

reticulum, releasing a flood of Ca2+ into the cytosol. Calcium can act through

several means to alter cell physiology.

i. Ca2+ may bind to calcium-dependent cytoplasmic enzymes that alter

cell metabolism.

ii. It may bind to calmodulin, which in turn can activate protein kinases.

iii. Ca2+ may bind to membrane channels and alter their permeability to

other solutes, in some cases altering the membrane potential.

g. In this way, hydrophilic hormones that cannot enter the cell can have marked

effects on metabolic activity by binding to a surface receptor.

h. Hormonal effects mediated through surface receptors are relatively quick

because the cell does not have to synthesize new proteins.

i. A hormone may employ more than one second messenger.

i. ADH uses the IP3–calcium system in smooth muscle but the cAMP

system in kidney tubules.

j. Insulin is different in that it binds to a plasma membrane enzyme, tyrosine

kinase, which directly phosphorylates cytoplasmic proteins.

E. One hormone molecule can trigger synthesis of an enormous number of enzyme molecules, a

mechanism called signal amplification. (p. 654) (Fig. 17.21)

1. One glucagon molecule can ultimately result in the production of 1 billion enzyme

molecules.


20

2. Hormones are therefore potent in very low concentrations, and target cells do not need

a great number of hormone receptors.

F. Target cells can modulate their sensitivity to a hormone by up-regulation and down-regulation

of receptors. (p. 654–655)

1. In up-regulation, a cell increases the number of receptors, becoming more sensitive to

a hormone. (Fig. 17.22a)

2. In down-regulation, a cell reduces its receptor number and becomes less sensitive to a

hormone. (Fig. 17.22b)

3. Hormone therapy often involves long-term use of abnormally high pharmacological

doses of a hormone, which may have undesirable side effects.

4. These side effects can come about in two ways:

a. Excess hormone may bind to receptor sites for other related hormones and

mimic their effects.

b. A target cell may convert one hormone into another, such as testosterone into

estrogen.

G. There are many hormones in the blood and tissue fluid. Therefore, no cell is exposed to only

one hormone. Cells ignore the majority of the hormones and respond to those that they have

receptors for, but most cells are sensitive to more than one hormone. In these cases, the

hormones may have three kinds of interactive effect: (pp. 654–656)

1. Synergistic effects—two or more hormones act together to produce an effect greater

than the sum of their separate effects.

2. Permissive effects—one hormone enhances the target organ’s response to a second

hormone secreted later, such as the effect of estrogen on the up-regulation of

progesterone receptors in the uterus.

3. Antagonistic effects—one hormone opposes the action of another, such as insulin and

glucagon. (Fig. 17.23)

H. Hormone clearance occurs when hormones are taken up and degraded by the liver and kidneys

and then excreted in bile or urine. (p. 655)

1. The rate of hormone removal is the metabolic clearance rate (MCR).

2. The length of time required to clear 50% of the hormone from the blood is its half-life.

V. Stress and Adaptation (pp. 656–657)

A. Stress is any situation that upsets homeostasis and threatens an individual’s physical or

emotional well-being. (p. 656)

B. The body reacts to stress with the stress response or general adaptation syndrome (GAS). This

typically involves elevated levels of epinephrine and cortisol. (p. 656)

C. Hans Selye showed that GAS occurs in three stages: the alarm reaction, the stage of resistance,

and the stage of exhaustion. (p. 656)


21

D. The alarm reaction is the initial response to stress and is mediated mainly by norepinephrine

from the sympathetic nervous system and epinephrine from the adrenal medulla. (p. 656–657)

1. These catecholamines prepare the body to take action such as when fighting or

escaping.

2. The consumption of stored glycogen occurs, which is important in the transition to the

next stage.

3. Angiotensin and aldosterone also increase, raising the blood pressure and promoting

sodium and water conservation.

E. The stage of resistance is entered when the glycogen reserves have been depleted and the

stressful situation has not been resolved. The first priority is to provide alternative fuels for

metabolism. Cortisol dominates this stage. (p. 657)

1. The hypothalamus secretes corticotropin-releasing hormone (CRH); the pituitary then

releases adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to

releases cortisol and other glucocorticoids.

2. Cortisol promotes the breakdown of fat and protein into glycerol, fatty acids, and

amino acids, providing the liver with materials for gluconeogenesis.

3. Cortisol also inhibits glucose uptake (glucose-sparing action) and protein synthesis.

a. Long-term elevation of cortisol secretion has an adverse effect on the immune

system.

i. It inhibits the synthesis of leukotrienes and prostaglandins,

suppresses antibody production, and kills immature T and B cells.

ii. Wounds heal poorly and a person becomes susceptible to infections.

iii. Stress can aggravate ulcers due to reduced resistance to bacteria and

because circulating epinephrine reduces the secretion of gastric mucus

and pancreatic bicarbonate.

4. Cortisol suppresses the secretion of sex hormones.

F. The stage of exhaustion sets in when the body’s fat reserves are depleted and stress overwhelms

homeostasis. (p. 657)

1. This stage may be marked by rapid decline and death.

2. With fat stores gone, the body relies primarily on protein breakdown to meet energy

needs, accompanied by wasting away of the muscles and weakening.

3. The adrenal cortex may stop producing glucocorticoids.

4. A state of hypertension may be the result of aldosterone secretion.

5. Aldosterone also hastens elimination of potassium and hydrogen ions, creating a state

of hypokalemia and alkalosis that can lead to nervous and muscular system dysfunctions.

VI. Eicosanoids and Paracrine Signaling (p. 657–658)


22

A. Paracrine messengers are chemical signals released by cells into the tissue fluid; they do not

travel by way of the blood but diffuse to nearby cells in the same tissue. (p. 657)

1. Histamine is released by mast cells alongside blood vessels in connective tissue, and it

diffuses to the smooth muscle of the blood vessel causing vasodilation.

2. Nitric oxide is released by endothelial cells of the blood vessel itself and also causes

vasodilation.

3. Catecholamines diffuse from the adrenal medulla to the cortex to stimulate

corticosterone secretion.

B. The eicosanoids are an important family of paracrine secretions. (p. 657–658)

1. These compounds have 20-carbon backbones derived from arachidonic acid, a

polyunsaturated fatty acid.

2. Some peptide hormones and other stimuli liberate arachidonic acid from a

phospholipid of the plasma membrane, and then two enzymes convert it to various

eicosanoids. (Fig. 17.24)

a. Lipoxygenase helps convert arachidonic acid to leukotrienes, eicosanoids that

mediate allergic and inflammatory reactions.

b. Cyclooxygenase converts arachidonic acid to three other types of eicosanoids.

i. Prostacyclin is produced by the walls of blood vessels, where it

inhibits blood clotting and vasoconstriction.

ii. Thromboxanes are produced by platelets and override prostacyclin to

stimulate vasoconstriction and clotting.

iii. Prostaglandins are a diverse group of eicosanoids that contain a

five-sided ring structure and were first found in semen and the prostate

gland. They are named PG plus a third letter indicating the type of ring

structure and a subscript indicating the number of double bonds, for

example PGF2α. (Fig. 17.24) (Table 17.7)

3. The action of some familiar drugs, such as NSAIDs, is due to their effect on the

pathways of eicosanoid synthesis.

Insight 17.3 Anti-Inflammatory Drugs

VII. Endocrine Disorders (pp. 659–664)

A. Hyposecretion is inadequate hormone release, and hypersecretion is excessive hormone

release. (p. 659)

1. If the hypothalamo–hypophyseal tract is severed, such as by a fractured sphenoid,

transport of oxytocin and ADH to the posterior pituitary is disrupted, leading to diabetes

insipidus.

2. Autoimmune diseases also can lead to hormone hyposecretion when endocrine cells

are attacked by autoantibodies. This is one of the causes of diabetes mellitus.


23

3. Some tumors result in the overgrowth of functional endocrine tissue and cause

hypersecretion. A pheochromocytoma is a tumor of the adrenal medulla that secretes

excessive amounts of epinephrine and norepinephrine. (Table 17.8)

4. Some autoimmune disorders can cause hypersecretion, such as toxic goiter (Graves

disease), in which autoantibodies mimic the effect of TSH on the thyroid. (Table 17.8)

B. Pituitary disorders affect growth. (p. 659)

1. Hypersecretion of growth hormone (GH) in adults causes acromegaly. (Fig. 17.25)

2. GH hypersecretion in childhood or adolescence causes gigantism.

3. GH hyposecretion in childhood or adolescence causes pituitary dwarfism. (Table 17.8)

a. Pituitary dwarfism is rarer now that genetically engineered human GH is

available.

C. Thyroid and parathyroid disorders are discussed together because of these glands’ proximity.

(p. 660)

1. Congenital hypothyroidism is hyposecretion of TH present from birth.

2. Severe or prolonged adult hypothyroidism can cause myxedema. Both congenital and

adult hypothyroidism can be treated with oral thyroid hormone.

3. A goiter is a pathological enlargement of the thyroid.

a. Endemic goiter is due to a dietary deficiency of iodine, required for TH

synthesis. (Fig. 17.26)

b. Without TH, the pituitary produces extra TSH, and the thyroid gland

undergoes hypertrophy.

4. The parathyroids are sometimes accidentally removed in thyroid surgery.

a. Without hormone replacement, hypoparathyroidism causes a rapid decline in

calcium levels, which can lead to a fatal, suffocating spasm of the larynx

(hypocalcemic tetany).

b. Hyperparathyroidism usually results from a tumor. It causes bone to become

soft and fragile, and raises the blood levels of calcium and phosphate, promoting

the formation of renal calculi (kidney stones) composed of calcium phosphate.

D. Adrenal disorders include Cushing syndrome and adrenogenital syndrome. (p. 660–661)

1. Cushing syndrome is excess cortisol secretion due to any of several causes, including

ACTH hypersecretion by the pituitary, ACTH-secreting tumors, or hyperactivity of the

adrenal cortex.

2. Cushing syndrome disrupts carbohydrate and protein metabolism, leading to

hyperglycemia, hypertension, muscle weakness, and edema.

a. Muscle and bone mass are lost as protein is catabolized.

b. Abnormal fat deposition between the shoulders or in the face may also occur.

c. These may also be effects of long-term hydrocortisone therapy. (Fig. 17.27)


24

3. Adrenogenital syndrome (AGS) is the hypersecretion of adrenal androgens and

commonly accompanies Cushing syndrome.

a. In children, AGS often causes enlargement of the penis or clitoris and the

premature onset of puberty.

b. Prenatal AGS can result in newborn girls exhibiting masculinized genitalia

and being misidentified as boys. (Fig. 17.28)

c. In women, AGS produces masculinizing effects such as increased body hair,

deepening of the voice, and beard growth.

E. Diabetes mellitus is the world’s most prevalent metabolic disease, occurring in about 7% of the

U.S. population and even more in Scandinavia and the Pacific Islands (pp. 661–662)

1. It is the leading cause of adult blindness, renal failure, gangrene, and limb amputations.

2. Diabetes mellitus (DM) can be defined as a disruption of carbohydrate, fat, and protein

metabolism resulting from hyposecretion or inaction of insulin.

a. Classic signs are the three polys: polyuria (excessive urine), polydipsia

(intense thirst), and polyphagia (ravenous hunger).

b. Three further clinical signs are revealed by blood and urine tests:

hyperglycemia (elevated blood glucose), glycosuria (glucose in the urine, from

which the disease gets its name), and ketonuria (ketones in the urine).

3. Normally the kidneys remove glucose from the urine and return it to the blood, via

glucose transporters (carrier-mediated transport).

4. In DM, the amount of glucose exceeds the transport maximum of the glucose

transporters and the excess glucose passes through into the urine.

5. Glucose and ketones in urine raise osmolarity, causing osmotic diuresis—water

remains in the tubules.

6. A person with untreated DM may pass 10 to 15 L of urine per day, compared with 1 or

2 L normally.

7. There are two forms of DM: type 1 (formerly juvenile or insulin-dependent) and type

2 (formerly adult or non-insulin-dependent). The older terms have been abandoned

because they are misleading given current knowledge.

8. Type 1 DM accounts for 5% to 10% of all cases in the U.S.

a. Several genes have been identified that predispose a person to type 1 DM.

b. When a genetically susceptible individual is infected by certain viruses, the

body produces autoantibodies that destroy pancreatic beta cells.

c. When 80% to 90% of the beta cells are gone, insulin falls to a critically low

level and hyperglycemia occurs.

d. It is usually diagnosed before age 30, but may occur later.


25

e. Victims require insulin to survive, usually by injection. Meal planning,

exercise, and self-monitoring of blood glucose are important aspects of the

treatment.

9. Type 2 DM accounts for 90% to 95% of all cases.

a. The chief problem is insulin resistance—unresponsiveness of the target cells

to the hormone.

b. There is clear evidence of a hereditary component, although no one gene can

be blamed for the disease.

c. There are differences in prevalence from one ethnic group to another.

i. Incidence is high among people of Native American, Hispanic, and

Asian descent.

d. It also has a tendency to run in families and has high concordance in

genetically identical twins.

e. Age, obesity, and a sedentary lifestyle are important risk factors.

i. As muscle mass is replaced with fat, a person become less able to

regulate blood glucose level.

f. Type 2 DM develops slowly and is usually diagnosed after age 40, but is

becoming more prevalent in young people because of childhood obesity.

g. Another factor besides the effects of muscle loss is that adipose tissue secretes

chemical signals that directly interfere with glucose transport into most cells.

h. Type 2 DM can often be successfully managed through a weight-loss program

of diet and exercise; if these prove inadequate, insulin therapy is also employed.

10. Pathogenesis of DM results from a combination of cell starvation and

hyperglycemia. a. The body metabolizes fat and protein when cells cannot

absorb glucose.

b. Prior to insulin therapy, victims wasted away in pain, hunger, and despair.

Children lived less than 1 year after diagnosis.

c. Rapid fat catabolism elevates blood levels of free fatty acids and their

breakdown products, the ketone bodies, and leads to ketonuria.

i. Ketonuria flushes Na+ and K+ from the body, creating electrolyte

deficiencies.

ii. Ketones in the blood lower the pH, causing ketoacidosis and a deep

gasping breathing called Kussmaul respiration, typical of terminal

diabetes. Ketoacidosis also produces diabetic coma.

d. DM leads to long-term degenerative cardiovascular disease.

i. Chronic hyperglycemia has negative effects on small to medium

blood vessels (microvascular disease) including atherosclerosis.


26

ii. Two common complications are blindness and renal failure, brought

on by arterial degeneration in retinas and kidneys.

iii. Death by renal failure is more common in type 1 than in type 2.

iv. In type 2, death due to heart failure from coronary artery disease is

more common.

e. DM also leads to long-term degenerative neurological disease.

i. Diabetic neuropathy is nerve damage resulting from impoverished

blood flow.

ii. This can lead to loss of sensation, incontinence, and erectile

dysfunction.

iii. Microvascular disease in the skin results in poor wound healing, so

that even a minor break easily becomes infected and even gangrenous,

especially in the feet.

iv. Neuropathy may make a person unaware of skin lesions so that they

are not treated quickly.

11. Other types of diabetes exist, such as diabetes insipidus, described earlier.

Insight 17.4 The Discovery of Insulin

Connective Issues: Effects of the Endocrine System on Other Organ Systems

Cross ReferencesAdditional information on topics mentioned in Chapter 17 can be found in the chapters listed below.

Chapter 1: Oxytocin and positive feedback cycles

Chapter 2: Enzyme–substrate interactions

Chapter 3: Effects of the sodium–potassium pump

Chapter 5: Exocrine glands

Chapter 7: Mechanisms of parathyroid hormone action

Chapter 12: Monoamines (biogenic amines) as neurotransmitters

Chapter 14: Hypothalamus structure and function

Chapter 18: Prostacyclin and thromboxane action

Chapter 21: The histology and immune functions of the thymus

Chapter 21: Eicosanoids and allergic and inflammatory reactions

Chapter 23: Other forms of diabetes

Chapter 26: Leptin and enteric hormone action

Chapters 27, 28: Anatomy of gonads

Chapter 28: Functions of estradiol and progesterone

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Saladin 5e Extended Outline · Web view2020. 9. 1. · a. Thyroid follicles are filled with a protein-rich colloid and lined with a simple cuboidal epithelium of follicular cells