c h a p t e r 16 part a 1. chief complaint: 8 year old girl with excessive thirst, frequent...

C H A P T E R 16

Part A

1

Chief Complaint: 8 year old girl with excessive thirst, frequent urination, and weight loss

History: History: Cindy Mallon, an 8-year-old girl in previously good health, has noticed that, in the past month, she is increasingly thirsty. She gets up several times a night to urinate, and finds herself gulping down glassfulls of water. At the dinner table, she seems to be eating twice as much as she used to, yet she has lost 5 pounds in the past month. In the past three days, she has become nauseated, vomiting on three occasions, prompting a visit to her pediatrician.

2

At the doctor's office, blood and urine samples are taken. The following lab results are noted:

blood glucose level = 545 mg/dl (normal 50-170 mg/dl)

blood pH level = 7.23 (normally 7.35-7.45) urine = tested positive for glucose and

ketone bodies (normally urine is free of glucose and ketone bodies)

3

Acts with nervous system to coordinate and integrate activity of body cells

Influences metabolic activities via hormones transported in blood

Response slower but longer lasting than nervous system

Endocrinology Study of hormones and endocrine organs

Slide 1

Controls and integrates Reproduction Growth and development Maintenance of electrolyte, water, and

nutrient balance of blood Regulation of cellular metabolism and

energy balance Mobilization of body defenses

Slide 2

Exocrine glands Nonhormonal substances (sweat, saliva) Have ducts to carry secretion to membrane

surface Endocrine glands

Produce hormones Lack ducts

Slide 3

Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands

Hypothalamus is Neuroendocrine organ Some have exocrine and endocrine functions

Pancreas, gonads, placenta Other tissues and organs that produce

hormones Adipose cells, thymus, and cells in walls of small

intestine, stomach, kidneys, and heart

Slide 4

Figure 16.1 Location of selected endocrine organs of the body.

Pineal glandHypothalamusPituitary gland

Thyroid glandParathyroid glands(on dorsal aspect of thyroid gland)Thymus

Adrenal glands

Pancreas

Gonads

• Testis (male)• Ovary (female)

Slide 5

Hormones: long-distance chemical signals; travel in blood or lymph

Autocrines: chemicals that exert effects on same cells that secrete them

Paracrines: locally acting chemicals that affect cells other than those that secrete them

Autocrines and paracrines are local chemical messengers; not considered part of endocrine system

Slide 6

Two main classes Amino acid-based hormones

Amino acid derivatives, peptides, and proteins Steroids

Synthesized from cholesterol Gonadal and adrenocortical hormones

Slide 7

Though hormones circulate systemically only cells with receptors for that hormone affected

Target cells Tissues with receptors for specific hormone

Hormones alter target cell activity

Slide 8

Hormone action on target cells may be to Alter plasma membrane permeability and/or

membrane potential by opening or closing ion channels

Stimulate synthesis of enzymes or other proteins

Activate or deactivate enzymes Induce secretory activity Stimulate mitosis

Slide 9

Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location1. Water-soluble hormones (all amino acid–

based hormones except thyroid hormone) Act on plasma membrane receptors Act via G protein second messengers Cannot enter cell

Slide 10

2. Lipid-soluble hormones (steroid and thyroid hormones) Act on intracellular receptors that directly

activate genes Can enter cell

Slide 11

cAMP signaling mechanism:1. Hormone (first messenger) binds to

receptor2. Receptor activates G protein3. G protein activates adenylate cyclase4. Adenylate cyclase converts ATP to cAMP

(second messenger) 5. cAMP activates protein kinases that

phosphorylate proteins

Slide 12

cAMP signaling mechanism Activated kinases phosphorylate various

proteins, activating some and inactivating others

cAMP is rapidly degraded by enzyme phosphodiesterase

Intracellular enzymatic cascades have huge amplification effect

Slide 13

Recall from Chapter 3 thatG protein signaling mechanismsare like a molecular relay race.

Hormone(1st messenger)

Receptor G protein Enzyme 2ndmessenger

Adenylate cyclase Extracellular fluid

G protein (Gs)

GDP

Receptor

Hormone (1st messenger) binds receptor.

Receptor activates G protein (Gs).

G protein activates adenylate cyclase.

Adenylate cyclase convertsATP to cAMP (2nd messenger).

Inactiveproteinkinase

Triggers responses of target cell (activatesenzymes, stimulatescellular secretion,opens ion channel, etc.)

Activeproteinkinase

cAMP activates protein kinases.

Cytoplasm

cAMP

GTP

GTPGTP

ATP

1

2 3 4

5

Slide 14



Receptor G protein Enzyme 2ndmessenger Hormone (1st messenger)

binds receptor.1

Extracellular fluid

Receptor

Cytoplasm

Slide 15




Extracellular fluid

Hormone (1st messenger) binds receptor.1

G protein (Gs)

GDP

Receptor

GTP

GTP


2

Cytoplasm

Slide 16





G protein (Gs)

GDP

Receptor




Cytoplasm

GTP

GTPGTP

1

2 3

Slide 17





G protein (Gs)

GDP

Receptor





Cytoplasm

cAMP

GTP

GTPGTP

ATP

1

2 3 4

Slide 18





G protein (Gs)

GDP

Receptor





Inactiveproteinkinase

Triggers responses of target cell (activatesenzymes, stimulatescellular secretion,opens ion channel, etc.)

Activeproteinkinase

cAMP activates protein kinases.

Cytoplasm

cAMP

GTP

GTPGTP

ATP

1

2 3 4

5

Slide 19

PIP2-calcium signaling mechanism Involves G protein and membrane-bound

effector – phospholipase C Phospholipase C splits PIP2 into two second

messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3)

DAG activates protein kinase; IP3 causes Ca2+ release

Calcium ions act as second messenger

Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin

Calcium-bound calmodulin activates enzymes that amplify cellular response

Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones

Some work without second messengers E.g., insulin receptor is tyrosine kinase

enzyme that autophosphorylates upon insulin binding docking for relay proteins that trigger cell responses

Steroid hormones and thyroid hormone1. Diffuse into target cells and bind with

intracellular receptors2. Receptor-hormone complex enters nucleus;

binds to specific region of DNA3. Prompts DNA transcription to produce

mRNA4. mRNA directs protein synthesis5. Promote metabolic activities, or promote

synthesis of structural proteins or proteins for export from cell

The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.

1

5

The receptor-hormone complex enters the nucleus.

The receptor- hormone complex binds a specific DNA region.

Binding initiates transcription of the gene to mRNA.

The mRNA directs protein synthesis.

New protein

Nucleus

mRNA

DNA

ReceptorBinding region

Receptor-hormonecomplex

Receptorprotein

Steroidhormone Plasma

membraneExtracellularfluid

Cytoplasm

2

3

4


1

Nucleus

Receptorprotein



Cytoplasm



1


Nucleus


Receptorprotein



Cytoplasm

2


1



Nucleus

DNA



Receptorprotein



Cytoplasm

2

3


1




Nucleus

mRNA

DNA



Receptorprotein



Cytoplasm

2

3

4


1

5




The mRNA directs protein synthesis.

New protein

Nucleus

mRNA

DNA



Receptorprotein



Cytoplasm

2

3

4

Target cells must have specific receptors to which hormone binds, for example ACTH receptors found only on certain cells

of adrenal cortex Thyroxin receptors are found on nearly all

cells of body

Target cell activation depends on three factors Blood levels of hormone Relative number of receptors on or in

target cell Affinity of binding between receptor and

hormone

Hormones influence number of their receptors Up-regulation—target cells form more

receptors in response to low hormone levels

Down-regulation—target cells lose receptors in response to high hormone levels

Blood levels of hormones Controlled by negative feedback systems Vary only within narrow, desirable range

Endocrine gland stimulated to synthesize and release hormones in response to Humoral stimuli Neural stimuli Hormonal stimuli

Changing blood levels of ions and nutrients directly stimulate secretion of hormones

Example: Ca2+ in blood Declining blood Ca2+ concentration

stimulates parathyroid glands to secrete PTH (parathyroid hormone)

PTH causes Ca2+ concentrations to rise and stimulus is removed

Figure 16.4a Three types of endocrine gland stimuli.

Humoral Stimulus

Hormone release caused by alteredlevels of certain critical ions ornutrients.

Stimulus: Low concentration of Ca2+ incapillary blood.

Parathyroidglands

Parathyroidglands

Capillary (low Ca2+

in blood)

Thyroid gland(posterior view)

PTH

Response: Parathyroid glands secreteparathyroid hormone (PTH), whichincreases blood Ca2+.


Humoral Stimulus


Parathyroidglands

Parathyroidglands

Capillary (low Ca2+

in blood)



Humoral Stimulus


Stimulus: Low concentration of Ca2+ incapillary blood.

Parathyroidglands

Parathyroidglands

Capillary (low Ca2+

in blood)


PTH

Response: Parathyroid glands secreteparathyroid hormone (PTH), whichincreases blood Ca2+.

Hormones stimulate other endocrine organs to release their hormones Hypothalamic hormones stimulate release

of most anterior pituitary hormones Anterior pituitary hormones stimulate

targets to secrete still more hormones Hypothalamic-pituitary-target endocrine

organ feedback loop: hormones from final target organs inhibit release of anterior pituitary hormones

Figure 16.4c Three types of endocrine gland stimuli.

Hormonal Stimulus

Hormone release caused by anotherhormone (a tropic hormone).

Stimulus: Hormones from hypothalamus.

Anteriorpituitarygland

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Response: Anterior pituitary gland secreteshormones that stimulate other endocrine glands to secrete hormones.


Hormonal Stimulus



Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus


Hormonal Stimulus


Stimulus: Hormones from hypothalamus.


Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Response: Anterior pituitary gland secreteshormones that stimulate other endocrine glands to secrete hormones.

Nerve fibers stimulate hormone release Sympathetic nervous system fibers

stimulate adrenal medulla to secrete catecholamines

Figure 16.4b Three types of endocrine gland stimuli.

Neural Stimulus

Hormone release caused by neural input.

Stimulus: Action potentials in preganglionicsympathetic fibers to adrenal medulla.

CNS (spinal cord)

Preganglionicsympatheticfibers

Medulla ofadrenal gland

Capillary

Response: Adrenal medulla cells secreteepinephrine and norepinephrine.


Neural Stimulus


CNS (spinal cord)



Capillary


Neural Stimulus


Stimulus: Action potentials in preganglionicsympathetic fibers to adrenal medulla.

CNS (spinal cord)



Capillary

Response: Adrenal medulla cells secreteepinephrine and norepinephrine.

Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms Example: under severe stress,

hypothalamus and sympathetic nervous system activated

body glucose levels rise

Nervous system can override normal endocrine controls

Hormones circulate in blood either free or bound Steroids and thyroid hormone are attached

to plasma proteins All others circulate without carriers

Concentration of circulating hormone reflects Rate of release Speed of inactivation and removal from body

Hormones removed from blood by Degrading enzymes Kidneys Liver

Half-life—time required for hormone's blood level to decrease by half

Varies from fraction of minute to a week

Some responses ~ immediate Some, especially steroid, hours to days Some must be activated in target cells

Limited Ranges from 10 seconds to several hours Effects may disappear as blood levels drop Some persist at low blood levels

Multiple hormones may act on same target at same time Permissiveness: one hormone cannot

exert its effects without another hormone being present

Synergism: more than one hormone produces same effects on target cell amplification

Antagonism: one or more hormones oppose(s) action of another hormone

Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe)

Neural tissue Anterior pituitary (lobe)

(adenohypophysis) Glandular tissue

Posterior pituitary (lobe) Downgrowth of hypothalamic neural tissue Neural connection to hypothalamus

(hypothalamic-hypophyseal tract) Nuclei of hypothalamus synthesize

neurohormones oxytocin and antidiuretic hormone (ADH)

Neurohormones are transported to and stored in posterior pituitary

Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2).

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

Oxytocin and ADH are stored in axon terminals in the posterior pituitary.

When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

1

2

3

4OxytocinADH

Posterior lobeof pituitary

Opticchiasma

Infundibulum(connecting stalk)

Hypothalamic-hypophyseal

tract

Axon terminals


Paraventricular nucleus

Hypothalamus

Supraopticnucleus

Inferiorhypophysealartery

Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.



1


Opticchiasma


Axon terminals


Hypothalamus

Supraopticnucleus


Hypothalamic-hypophyseal

tract




1

2


Opticchiasma


Axon terminals


Hypothalamus

Supraopticnucleus


Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.Hypothalamic-

hypophysealtract





1

2

3


Opticchiasma


Axon terminals


Hypothalamus

Supraopticnucleus



hypophysealtract





When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

1

2

3

4OxytocinADH


Opticchiasma


Axon terminals


Hypothalamus

Supraopticnucleus



hypophysealtract


Anterior Lobe: Originates as out-pocketing of oral mucosa Vascular connection to hypothalamus

Hypophyseal portal system Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus Carries releasing and inhibiting hormones to

anterior pituitary to regulate hormone secretion

Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2).

Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary.

In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.

GH, TSH, ACTH,FSH, LH, PRL

Anterior lobeof pituitary

When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus.

Hypophysealportal system

• Primary capillary plexus• Hypophyseal portal veins• Secondary capillary plexus

Superiorhypophyseal

artery


Hypothalamus Hypothalamicneurons synthesizeGHRH, GHIH, TRH,CRH, GnRH, PIH.

A portal system is two capillary plexuses (beds) connected by veins.

12

3







Superiorhypophyseal

artery




1








Superiorhypophyseal

artery




12



In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.






Superiorhypophyseal

artery




12

3

Oxytocin and ADH Each composed of nine amino acids Almost identical – differ in two amino acids

Strong stimulant of uterine contraction Released during childbirth Hormonal trigger for milk ejection Acts as neurotransmitter in brain

Inhibits or prevents urine formation Regulates water balance Targets kidney tubules reabsorb

more water Release also triggered by pain, low

blood pressure, and drugs Inhibited by alcohol, diuretics High concentrations vasoconstriction

Diabetes insipidus ADH deficiency due to hypothalamus or

posterior pituitary damage Must keep well-hydrated

Syndrome of inappropriate ADH secretion (SIADH) Retention of fluid, headache, disorientation Fluid restriction; blood sodium level

monitoring

Growth hormone (GH) Thyroid-stimulating hormone (TSH)

or thyrotropin Adrenocorticotropic hormone

(ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL)

All are proteins All except GH activate cyclic AMP

second-messenger systems at their targets

TSH, ACTH, FSH, and LH are all tropic hormones (regulate secretory action of other endocrine glands)

Produced by somatotropic cells Direct actions on metabolism

Increases blood levels of fatty acids; encourages use of fatty acids for fuel; protein synthesis

Decreases rate of glucose uptake and metabolism – conserving glucose

Glycogen breakdown and glucose release to blood (anti-insulin effect)

Indirect actions on growth Mediates growth via growth-promoting

proteins – insulin-like growth factors (IGFs) IGFs stimulate

Uptake of nutrients DNA and proteins Formation of collagen and deposition of bone

matrix Major targets—bone and skeletal muscle

GH release chiefly regulated by hypothalamic hormones Growth hormone–releasing hormone (GHRH)

Stimulates release Growth hormone–inhibiting hormone (GHIH)

(somatostatin) Inhibits release

Ghrelin (hunger hormone) also stimulates release

Hypersecretion In children results in gigantism In adults results in acromegaly

Hyposecretion In children results in pituitary dwarfism

Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH).

Hypothalamussecretes growthhormone–releasinghormone (GHRH), andGHIH (somatostatin)

Anteriorpituitary

Inhibits GHRH release

Stimulates GHIH release

Inhibits GH synthesisand release

Feedback

Indirect actions(growth-promoting)

Liver andother tissues

Insulin-like growthfactors (IGFs)

Produce

Effects

Skeletal ExtraskeletalFat

metabolismCarbohydratemetabolism

Direct actions(metabolic,anti-insulin)

Effects

Growth hormone (GH)

Increased cartilageformation and

skeletal growth

Increased proteinsynthesis, andcell growth and

proliferation

Increasedfat breakdown

and release

Increased bloodglucose and otheranti-insulin effects

Increases, stimulates

Initial stimulus

Reduces, inhibits

Physiological response

Result

Figure 16.7 Disorders of pituitary growth hormone.

Produced by thyrotropic cells of anterior pituitary

Stimulates normal development and secretory activity of thyroid

Release triggered by thyrotropin-releasing hormone from hypothalamus

Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus

Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroidhormones

Target cellsStimulates

Figure 16.8 Regulation of thyroid hormone secretion.

Inhibits

Secreted by corticotropic cells of anterior pituitary

Stimulates adrenal cortex to release corticosteroids

Regulation of ACTH release Triggered by hypothalamic corticotropin-

releasing hormone (CRH) in daily rhythm Internal and external factors such as fever,

hypoglycemia, and stressors can alter release of CRH

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

Secreted by gonadotrophs of anterior pituitary

FSH stimulates gamete (egg or sperm) production

LH promotes production of gonadal hormones

Absent from the blood in prepubertal boys and girls

Regulation of gonadotropin release Triggered by gonadotropin-releasing

hormone (GnRH) during and after puberty Suppressed by gonadal hormones

(feedback)

Secreted by prolactin cells of anterior pituitary

Stimulates milk production Role in males not well understood

Regulation of PRL release Primarily controlled by prolactin-inhibiting

hormone (PIH) (dopamine) Blood levels rise toward end of

pregnancy Suckling stimulates PRL release and

promotes continued milk production Hypersecretion causes inappropriate

lactation, lack of menses, infertility in females, and impotence in males

c h a p t e r 16 part a 1. chief complaint: 8 year old girl with excessive thirst, frequent...

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