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Unit XI ENDOCRINE SYSTEM

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Title: Unit XI ENDOCRINE SYSTEM


1
Unit XIENDOCRINE SYSTEM
Biology 220 Anatomy Physiology I
Chapter 17, pp. 608-649
E. Gorski/ E. Lathrop-Davis/ S. Kabrhel
2
Comparison of Nervous and Endocrine Systems
NOTE Nervous and endocrine systems work together
to coordinate and integrate activities of body
(homeostasis)
3
Functions of Endocrine System
  • 1. Reproduction
  • 2. Growth and development
  • 3. Response to stress
  • 4. Maintenance of fluid (water), electrolyte and
    nutrient balance
  • 5. Regulation of cellular metabolism and energy

4
Organs of the Endocrine System
  • 1. Pituitary gland
  • 2. Hypothalamus (neuroendocrine)
  • 3. Pineal gland
  • 4. Thyroid gland
  • 5. Parathyroid gland
  • 6. Thymus gland
  • 7. Adrenal gland
  • 8. Pancreas (also has exocrine function)
  • 9. Gonads (testes or ovaries - also have exocrine
    functions)

Fig. 17.4, p.616
5
Topics
  • Hormone
  • Types
  • Modes of Action
  • Target cell activation
  • Control
  • Specific glands, their hormones, and disorders
  • Pituitary
  • Thyroid
  • Parathyroid
  • Adrenal
  • Pancreas
  • Thymus
  • Gonads (testes and ovaries)
  • General Adaptation Syndrome

6
Hormones
  • chemicals
  • secreted by endocrine gland cells into blood (by
    way of interstitial fluid)
  • regulate metabolic functions of other cells
    (called target cells)
  • carried to all cells, but action is specific to
    cells that have receptors for the hormone
  • specificity of bodys response to hormone depends
    on how many cells have the receptor (highly
    specific if few cells respond e.g., ACTH
    diffuse action if many respond e.g., thyroxine)

7
Chemical Types of Hormones
  • Amino-acid based (amino acids, short or long
    peptides, proteins)
  • e.g., insulin, growth hormone, prolactin
  • Steroids - lipid derivatives of cholesterol
  • e.g., hormones from gonads (testosterone,
    estrogen)
  • e.g., hormones from adrenal cortex
    (adrenocortical hormones)
  • Eicosanoids - locally-secreted, locally-acting
    hormones secreted by all cell membranes (e.g.,
    prostaglandins, which increase blood pressure and
    contribute to uterine contraction)

8
Types of Changes in Target Cells
  • plasma membrane permeability changes (opening of
    protein channels may change membrane potential)
  • activation of genes for increased protein
    synthesis, including enzymes
  • activation or deactivation of enzymes already
    present
  • secretion of cellular products
  • stimulation of cell division (mitosis)

9
Mechanisms of Action
  • action in target cell depends on receptor
  • receptor may be
  • in plasma membrane
  • second messenger mechanisms
  • used by most amino acid-based hormones (water
    soluble)
  • intracellular (in cytoplasm or nucleus)
  • direct gene activation
  • used by steroids and thyroid hormones (lipid
    soluble)

10
Mechanisms of Action Steroids
  • bind to intracellular receptors
  • hormone diffuses through plasma membrane and
    makes its way to nucleus
  • gt where it binds with intracellular receptor to
    form hormone-receptor complex
  • gt hormone-receptor complex interacts with
    chromatin (DNA) to affect gene activity (turn
    genes on or off)
  • gt synthesis of mRNA
  • gt synthesis of protein

11
Steroid Signaling
Fig. 17.2, p. 613
12
Mechanism of ActionThyroid Hormone
  • similar to mechanism for steroid hormones
  • diffuses across plasma membrane
  • diffuses into nucleus where it interacts with
    intracellular receptors to activate genes for
    proteins (enzymes) involved in cellular
    respiration (glycolysis)
  • also, binds to receptors at mitochondria to
    activate genes for proteins involved in cellular
    respiration (Krebs cycle and electron transport
    chain)

13
Mechanisms of Action Other Hormones
  • plasma membrane receptor
  • used by most amino acid-based hormones
  • interaction of hormone with plasma membrane
    receptor results in activation of second
    messenger systems (cyclic AMP or PIP-calcium)
  • activation of second messenger has cascade effect
    resulting in
  • enzyme activation, or
  • membrane permeability changes or secretion

14
Membrane Receptor Mechanisms1. Cyclic AMP
(cAMP) Signaling
  • interaction of hormone with receptor
  • gt activates G protein (cleaves phosphate from
    GTP)-gt excitation
  • gt G protein activates adenylate cyclase
  • gt adenylate cyclase forms cAMP from ATP
  • gt cAMP activates protein kinases
  • gt protein kinases activate (or inhibit) other
    proteins by phosphorylation
  • gt cAMP degraded by enzyme
  • slightly different G protein inactivates
    adenylate cyclase - associated with different
    hormone receptor
  • Link to animation http//student.ccbc.cc.md.us/c_
    anatomy/animat/cAMP.htm

15
cAMP Signaling Mechanism
Fig. 17.1, p. 611
16
Membrane Receptor Mechanisms2. PIP-Calcium
Signaling
  • interaction of hormone with receptor --gt
    activates membrane-bound enzyme phospholipase
  • gt phospholipase cleaves PIP2 (phosphatidyl
    inositol diphosphate) into diacylglycerol (DAG)
    and IP3 -- each of which acts as a second
    messenger
  • diacylglycerol (DAG) activates protein kinases
  • IP3 (inositol triphosphate) causes release of
    Ca2 into cytoplasm (from endoplasmic reticulum
    or other storage areas) --gt Ca2 acts as third
    messenger

17
PIP-Calcium Mechanism (cont)
  • -gt Ca2 (third messenger)
  • changes enzyme activity and plasma membrane
    channels, or
  • binds to calmodulin (intracellular regulatory
    protein) --gt activates enzymes
  • see Fig. 17.2 for examples of proteins that act
    through membrane-receptors and 2nd messengers

18
PIP-Calcium Signaling Mechanism
Fig. 17.1, p. 612
19
Factors Affecting Target Cell Activation
  • a. blood levels of hormone, which depend on
  • rate of hormone release
  • rate of deactivation (by target cell or liver)
  • b. affinity of hormone for receptor
  • greater affinity means greater association --gt
    greater effect
  • c. number of receptors available

20
Factors Affecting Target Cell Activation (cont)
  • c. number of receptors available
  • up-regulation increase in blood level of
    specific hormone (normally present at low levels)
    causes cells to make more receptors
  • down-regulation prolonged exposure to high level
    of specific hormone --gt cells remove some
    receptors
  • --gtreturn to normal response level
  • cross-regulation influence of one hormone on
    number of receptors for another hormone e.g.,
    progesterone causes uterus to make fewer estrogen
    receptors estrogen causes uterus to make more
    progesterone receptors

21
Hormone Removal
  • hormones may be
  • degraded by specific enzymes within target cells
  • removed from blood by kidneys (excreted in urine)
  • degraded by liver (excreted in urine and feces)
  • half-life - time for 1/2 of hormone to be removed
    (from a fraction of a minute to 30 minutes)
  • onset - time from release to action (minutes
    amino acid-based to days steroids)
  • duration of action - how long the effects last
    (20 minutes to several hours)

22
Control of Hormone Release
  • Humoral control
  • Neural control
  • Hormonal control

23
Control of Hormone Release Humoral
  • Hormone released in response to changing blood
    levels of ion or nutrient (negative feedback)
  • parathyroid glands detects low blood Ca2 ? PTH
    ? raises blood Ca2
  • thyroid (parafollicular cells) detect high blood
    Ca2--gtcalcitonin--gtdecrease blood Ca2

Fig.17.3, p615
24
Control of Hormone Release Humoral
  • Other examples
  • pancreas
  • beta cells detect high blood glucose ? insulin ?
    decreases blood glucose
  • alpha cells detect low blood glucose ?glucagon ?
    raises blood glucose
  • zona glomerulosa (of adrenal cortex) detects low
    blood Na or high blood K ? aldosteronetthy, ?
    K

25
Control of Hormone Release Neural
  • Hormone released in response to nerve impulse
  • preganglionic fibers of sympathetic division ?
    stimulate release of catecholamines (epinephrine,
    norepinephrine) from adrenal medulla
  • impulses from hypothalamus result in release of
    oxytocin or ADH from posterior pituitary

Fig. 17.3, p. 615
Fig. 17.5, p. 617
26
Control of Hormone Release Hormonal
  • Hormone produced by one endocrine gland (or
    hypothalamus) affects secretion of hormone by
    another endocrine gland
  • hypothalamus acts as overall coordinator ?
    releases regulatory hormones (releasing hormones
    or inhibitory hormones) ? affects anterior
    pituitary
  • anterior pituitary, when stimulated, secretes
    hormones that affect other glands (e.g., TSH
    thyroid stimulating hormone stimulates release
    of thyroid hormones from thyroid gland)

27
Hormonal Control Role of Hypothalamus
  • Releasing hormones from hypothalamus stimulate
    secretion from anterior pituitary
  • Inhibitory hormones from hypothalamus inhibit
    secretion by anterior pituitary
  • Impulses from hypothalamus cause release of
    hormones from posterior pituitary

Fig. 17.5, p. 617
28
Hormone Control - Misc.
  • nervous system can override normal endocrine
    control
  • e.g., in fight-or-flight response, sympathetic
    impulses result in release of epinephrine and
    norepinephrine from adrenal medulla --gt increases
    blood glucose levels to maintain fuel supply
    during stress or exertion (overrules effect of
    insulin on blood glucose level)

29
Organs of the Endocrine System and Their Products
  • The following major glands will be covered one at
    a time with their products
  • 1. Pituitary gland / Hypothalamus
  • 2. Thyroid gland
  • 3. Parathyroid gland
  • 4. Adrenal gland
  • 5. Pancreas (also has exocrine function)
  • 6. Gonadal hormones (ovaries and testes)
  • 7. Thymus

Fig. 17.4, p. 616
30
1. Pituitary Gland (Hypophysis)
  • located in sella turcica of sphenoid bone (in
    cranial cavity), inferior to hypothalamus
  • consists of two lobes
  • A. neurohypophysis ( posterior pituitary)
  • attached to hypothalamus by infundibulum
  • contains axons and axon terminals of
    neurosecretory cells whose cell bodies are in
    hypothalamic nuclei
  • B. adenohypophysis ( anterior pituitary)
  • consists of glandular epithelium

http//www.usc.edu/hsc/dental/ghisto/end/c_1.html
31
Pituitary Development
From roof of mouth
http//calloso.med.mun.ca/tscott/head/pit.htm
32
A. Neurohypophysis (Posterior Pituitary)
  • consists of nerve fibers (axons of neurosecretory
    cells with cell bodies in hypothalamus) and
    pituicytes (glial cells that support nerve
    fibers)
  • acts primarily as a storage and releasing area
    for hormones actually made in hypothalamic nuclei
  • hormones released in response to impulses from
    hypothalamus (neural control)
  • hormones are short amino acid chains (peptides)
  • oxytocin
  • antidiuretic hormone (ADH or vasopressin)

33
A. NeurohypophysisOxytocin (OT)
  • action, in pregnant or nursing women
  • stimulates contraction of smooth muscle of
    uterine wall during labor and delivery
  • stimulates ejection of milk in lactating mothers
  • action, in men and non-pregnant women, may be
    involved in sexual arousal and orgasm

34
A. NeurohypophysisOxytocin (OT)
  • control
  • during labor/delivery, positive feedback
    stretching of uterus/cervix --gt sensory impulses
    to hypothalamus --gt increased secretion of OT --gt
    increased contraction
  • suckling sucking of infant on breast --gt sensory
    to hypothalamus --gt oxytocin release --gt release
    of milk

35
A. Neurohypophysis Antidiuretic Hormone (ADH)
  • action antidiuretic hormone (ADH) directly
    affects blood pressure - acts as powerful
    vasoconstrictor --gt increases blood pressure
    (hence name vasopressin)
  • action affects water balance (indirect affect on
    blood pressure) - acts on tubules of kidney to
    increase reabsorption of water ? less water lost
    in urine

36
A. Neurohypophysis ADH
  • disorders
  • hyposecretion due to damage of hypothalamic
    nucleus or neurohypophysis--gt diabetes insipidus
    - excessive urine production (polyuria) and
    thirst
  • hypersecretion --gt SIADH (syndrome of
    inappropriate ADH secretion) - water retention,
    headache, cerebral edema, weight gain,
    hypoosmolarity

37
Antidiuretic Hormone (ADH) Control
  • neural control increased electrolyte (NaCl)
    concentration --gt affects (supraoptic) nucleus in
    hypothalamus --gt impulse to neurohypophysis --gt
    release of ADH --gt increased water reabsorption
    --gt decrease in electrolyte concentration
  • other stimuli pain, low BP, morphine,
    barbiturates, nicotine, aldosterone (hormone from
    adrenal cortex - hormonal control)
  • inhibition alcohol (results in more urine
    production and, potentially, dehydration)
  • diuretic drugs - some act to supress ADH
    secretion used to treat hypertension and
    congestive heart failure

38
B. Adenohypophysis (Anterior Pituitary)
  • linked to hypothalamus via hypophyseal portal
    system (capillary networks and small veins)
  • carries regulatory hormones from hypothalamus to
    pituitary
  • releasing hormones stimulate secretion of
    pituitary hormones
  • inhibitory hormones inhibit secretion
  • consists of epithelial cells
  • all hormones produced are proteins
  • tropic hormones - affect some endocrine glands or
    provide maintenance oversight for other organs

39
B. AdenohypophysisGrowth Hormone (GH)
  • highest levels during evening and sleep
  • action stimulates increased rate of protein
    synthesis leading to cell growth and division
  • bones and skeletal muscle respond more than other
    body cells
  • action stimulates use of fat as energy source
    and decreases rate of glucose uptake and glucose
    metabolism (diabetogenic effect spares
    glucose)
  • control
  • release stimulated by GHRH (growth hormone
    releasing hormone) from hypothalamus
  • inhibited by GHIH (from hypothalamus) and
    somatomedins (produced by liver under GH
    stimulation)

40
Growth Hormone (GH) Disorders
  • Disorders
  • hypersecretion
  • gigantism (in children)
  • up to 8 tall, normal body proportions
  • acromegaly (after epiphyseal plates close)
  • enlargement of extremities and face, thickening
    of soft tissue
  • hyposecretion
  • pituitary dwarfism - in children, up to 4 tall
  • progeria - premature aging, atrophy of body
    tissues

See Fig. 17.6, p. 619
41
B. Adenohypophysis Prolactin (PRL)
  • action
  • stimulates milk production in mammary glands
  • helps stimulate development of mammary glands
    (along with other hormones)
  • in males, may help regulate testosterone
    production
  • control
  • stimulation PRH (prolactin-releasing hormone
    from hypothalamus), high estrogens,
    breast-feeding
  • inhibition PIH (hypothalamus), stimulated by
    rising PRL levels, low estrogen

42
B. AdenohypophysisProlactin (PRL)
  • Disorders
  • hyperprolactinemia hypersecretion due to
    adenohypophyseal tumors results in galactorrhea,
    lack of menses and infertility in women,
    impotence in men

43
B. Adenohypophysis Thyroid-Stimulating Hormone
(TSH)
  • TSH thyrotropin
  • action
  • stimulates secretion of hormones from thyroid
    gland (T4 and T3) also stimulates development of
    thyroid in youth
  • control
  • release stimulated by TRH (thyroid releasing
    hormone from hypothalamus)
  • inhibited by rising levels of thyroid hormones
    and by GHIH

44
B. Adenohypophysis Adrenocorticotropic hormone
(ACTH)
  • ACTHcorticotropin
  • action stimulates release of hormones from
    adrenal cortex
  • control
  • release stimulated by CRH (corticotropin-releasing
    hormone from hypothalamus)
  • release inhibited by rising levels of
    glucocorticoids from adrenal cortex

45
B. AdenohypophysisGonadotropins
  • regulate activity and secretion by gonads (testes
    in males ovaries in females)
  • control
  • stimulated by GnRH (gonadotropin-releasing
    hormone from hypothalamus)
  • release of GnRH is inhibited by rising levels of
    estrogens, progestins and androgens
    (testosterone)
  • two important hormones
  • FSH
  • LH

46
GonadotropinsFollicle-Stimulating Hormone (FSH)
  • action
  • females (ovaries) - stimulates development of
    ovarian follicles and estrogen production
  • males (testes) - stimulates sperm production and
    development
  • inhibited by inhibin and testosterone from testes
    (feedback to hypothalamus and anterior pituitary)
    and estrogen, progesterone and inhibin from
    ovaries (feedback to anterior pituitary)

47
GonadotropinsLuteinizing Hormone (LH)
  • LHlutropin
  • action
  • females (ovaries) - induces ovulation stimulates
    secretion of estrogens and progestins (e.g.,
    progesterone)
  • males (testes) - stimulates production of
    androgens (e.g., testosterone )
  • inhibited by estrogen, progesterone and inhibin
    form ovaries (feedback to anterior pituitary) and
    by inhibin and testosterone from testes (feedback
    to hypothalamus and anterior pituitary)

48
2. Thyroid Gland
  • located anteriorly in cervical region, just
    inferior to thyroid cartilage two lobes
    connected by thin isthmus
  • largest purely endocrine gland in body
  • consists of follicles (cuboidal or simple
    squamous epithelium) filled with colloid
    (combination of protein thyroglobulin
    containing amino acid tyrosine building block of
    thyroid hormones)
  • parafollicular cells produce calcitonin

http//www.usc.edu/hsc/dental/ghisto/end/c_26.html
49
2. Thyroid Gland T4 and T3
  • hormones based on amino acid tyrosine (differ in
    number of iodine ions)
  • thyroxine (tetraiodothyronine T4) and
  • triiodothyronine (T3)
  • T3 is 10x more active, but less common (T4
    accounts for about 90 of all thyroid hormone)
  • much T4 converted to T3 by liver, kidneys, some
    other tissues

50
2. Thyroid Gland T4 and T3
  • affect metabolic rate of every cell in the body,
    except brain, spleen, testes, uterus and thyroid
    gland
  • affect other activities within these organs and
    glands
  • readily cross membranes (diffuse through plasma
    membrane to bind to mitochondrial receptors and
    receptors in nucleus)

51
2. Thyroid Gland
Fig. 17.8, p. 625
52
T4 and T3 Actions
  • increase synthesis of enzymes involved in
    cellular respiration --gt increase basal metabolic
    rate
  • increases glucose oxidation --gt ATP synthesis
  • increases ATP synthesis in cytoplasm and by
    mitochondria
  • results in increased heat production (calorigenic
    effect)
  • work with GH to promote normal tissue growth and
    development, especially important to
    growth/development of CNS, skeletal and
    reproductive systems

53
T4 and T3 Control
  • release stimulated by TSH (thyroid-stimulating
    hormone from adenohypophysis)
  • release of TSH stimulated by TRH from
    hypothalamus
  • release of TRH is stimulated by cold, pregnancy,
    low thyroxine
  • release inhibited by GHIH, high glucocorticoid
    levels, high sex hormone levels, high iodine

54
Hypothyroidism
  • too little thyroid hormone (thyroid gland defect,
    inadequate TSH, TRH, or iodine)
  • Hashimotos thyroid autoimmune disorder in
    which thyroid is attacked and function decreases
  • myxedema - low BMR, constipation, puffy eyes,
    edema, lethargy, mental sluggishness
  • endemic goiter - enlargement of thyroid gland
    usually due to lack of sufficient iodine
  • cretinism - genetic deficiency of thyroid gland
    or lack of dietary iodine during development
    resulting in mental retardation, disproportionate
    growth, short body with thick tongue and neck
  • treatment - reversed by iodine supplements or
    hormone replacement therapy

55
Hyperthyroidism
  • too much thyroid hormone (thyrotoxicosis)
  • Graves disease - autoimmune disease in which
    abnormal antibodies similar to TSH mimic its
    function and continuously stimulate release of
    thyroid hormones results in high BMR, sweating,
    rapid heart rate, weight loss, restlessness, mood
    shifts, fatigues easily, limited energy also
    toxic goiter
  • exophthalmos - protrusion of eyeballs, fibrous
    tissue become edematous (swollen)
  • treatments - removal of thyroid gland or
    irradiation
  • patient must be on synthetic thyroid hormone the
    rest of his/her life

56
2. Thyroid Gland Calcitonin (CT)
  • polypeptide produced by parafollicular cells
  • actions decreases blood calcium levels by
  • stimulating osteoblasts (Ca2 uptake and
    incorporation into bone)
  • inhibiting osteoclast activities (osteoclasts
    break down bone matrix releasing calcium)
  • control responds directly to blood calcium
    levels
  • very rapid effect
  • probably more important during childhood when it
    stimulates bone growth
  • important because at high blood Ca2, membranes
    become less permeable to Na

57
3. Parathyroid Glands
  • 2 paired structures on posterior of thyroid gland
  • oxyphyil cells - function unknown
  • chief cells secrete parathyroid hormone (PTH
    protein)
  • actions increases blood Ca2 by
  • stimulating osteoclast activity (which break down
    bone matrix) while inhibiting osteoblasts (which
    form bone matrix)
  • stimulating increased reabsorption of Ca2 by
    kidney
  • indirectly stimulating increased absorption of
    Ca2 by small intestine by causing secretion of
    calcitrol form kidneys

58
3. Parathyroid Glands
Fig. 17.10, p. 628
Fig. 17.11, p. 629
http//www.usc.edu/hsc/dental/ghisto/end/c_32.html
59
Hyperparathyroidism
  • rare caused by parathyroid gland tumor
  • results in hypercalcemia (excess Ca2 levels in
    blood) --gt depression of nervous system (because
    of effect on sodium permeability), abnormal
    reflexes, skeletal muscle weakness, nausea,
    vomiting, kidney stones, calcium deposits in soft
    tissues bones become soft

60
Hypoparathyroidism
  • trauma to or removal of parathyroid gland
  • results in hypocalcemia (low blood Ca2) --gt
    neurons become too excitable --gt muscle tetany
    --gt spasms/cramps --gt respiratory paralysis --gt
    death

61
4. Adrenal Glands
  • located in abdominal cavity against back wall
    (retroperitoneal), superior to kidney
  • surrounded by connective tissue capsule
  • two regions
  • cortex - outer region, glandular, three zones
  • zona glomerulosa - outer zone
  • zona fasciculata - middle zone
  • zona reticularis - inner zone
  • medulla - inner region, modified neural tissue
    (develops from same tissue in embryo as
    ganglionic postganglionic neurons of
    sympathetic division)

62
4. Adrenal Gland Development
http//sprojects.mmi.mcgill.ca/embryology/ug/Adren
al_Stuff/Normal/zones.html
63
4. Adrenal Gland Regions and Zones
Fig. 17.12, p. 630
64
Adrenal Cortex Zona Glomerulosa
  • produces steroid hormones based on cholesterol
  • mineralocorticoids - ion (and water) balance
  • main hormone is aldosterone
  • action
  • stimulates reabsorption of Na and secretion of
    K from kidney, sweat glands, salivary glands,
    pancreas
  • secondarily, increases water reabsorption in
    kidney (water follows Na)

65
Adrenal Cortex Zona Glomerulosa
  • control
  • aldosterone release stimulated by
  • high K, low Na
  • angiotensin II (result of renin-angiotensin
    pathway stimulated by low blood pressure),
  • ACTH (when under severe stress)
  • inhibited by low K, high Na

Fig. 17.13, p. 632
66
Adrenal Cortex Zona Glomerulosa
  • Disorders
  • aldosteronism hypersecretion (adrenal tumor)
  • increased water and Na reabsorption --gt
    hypertension, edema
  • loss of K --gt disruption of neural and muscle
    function

67
Adrenal Cortex Zona Glomerulosa
  • Disorders
  • Addisons Disease hyposecretion glucocorticoids
    and mineralocorticoids
  • results in decreased Na and water reabsorption,
    increased blood K --gt low blood volume --gt
    hypotension, dehydration
  • changes in membrane potentials --gt disruption in
    neural and muscular function
  • also decreased cortisol secretion by zona
    fasciculata --gt decreased blood glucose levels
    (especially during prolonged stress)

68
Adrenal Cortex Zona Fasciculata
  • glucocorticoids - effects on glucose metabolism
  • main hormone is cortisol (hydrocortisone)
  • actions
  • maintains blood glucose levels, especially in
    times of stress, by
  • promoting gluconeogenesis (making new glucose in
    liver) and use of alternative fuels by other
    cells (saves glucose for the brain)
  • anti-inflammatory decrease immune response
  • can be used clinically to treat allergic
    reactions (e.g., poison ivy), rheumatoid arthritis

69
Adrenal Cortex Zona Fasciculata
  • Control
  • stimulated by ACTH
  • inhibited by cortisol (inhibits secretion of CRH
    from hypothalamus)
  • blood levels peak in the morning
  • Disorders
  • Addisons Disease
  • - hyposecretion of glucocorticoids and
    mineralocorticoids

70
Zona Fasciculata Cushings Disease
  • hypersecretion of glucocorticoids
  • caused by hypersecretion of ACTH due to tumor in
    ZF, pituitary, lungs, kidneys, or pancreas
  • suppresses glucose metabolism resulting in
  • hyperglycemia (elevated glucose steroid
    diabetes),
  • stimulates lipid metabolism (weight loss),
  • loss of muscle and bone mass,
  • buffalo neck and moon face (fat
    redistribution),
  • anti-inflammatory effects (mask infection)
  • water and salt retention (effect of aldosterone
    hypersecretion --gt water retention --gt
    hypertension)

71
Adrenal Cortex Zona Reticularis
  • gonadocorticoids
  • most are androgens (male sex hormones) -
    converted to testosterone small amounts of
    estrogens
  • actions may contribute to onset of puberty
    (levels rise between 7 and 13 years of age exact
    function compared to hormones from ovaries or
    testes unclear)
  • control stimulated by ACTH

72
Adrenal Cortex Zona Reticularis
  • hypersecretion results in
  • masculinization and masculine pattern of hair
    distribution in females
  • in males - rapid maturation of reproductive
    organs, secondary sex characteristics
    hypersecretion of estrogens causes feminization
    and gynecomastia (enlarged breasts)

73
Adrenal Medulla
  • chromaffin cells (modified neurons - arise from
    same embryonic tissue as postganglionic neurons
    of sympathetic division)
  • catecholamines - epinephrine (80), norepi (NE)
  • control secretion stimulated by preganglionic
    fibers of sympathetic nerves during
    flight-or-fight response

74
Adrenal Medulla
  • actions
  • epinephrine (more potent) - increases HR (beta
    receptors), bronchodilation (in lungs), increased
    blood glucose (breakdown of glycogen in liver and
    skeletal muscle, and breakdown of adipose tissue)
  • NE - peripheral vasoconstriction --gt increased BP

75
5. Pancreas
  • has both exocrine (acini secrete digestive
    enzymes) and endocrine function (islets of
    Langerhans)
  • control responds to blood glucose levels
    (humoral)
  • hormones are polypeptides (proteins)

http//www.usc.edu/hsc/dental/ghisto/end/c_49.html
76
5. Pancreas
  • major cell types
  • alpha cells secrete glucagon
  • beta cells secrete insulin
  • delta cells secrete somatostatin (which inhibits
    insulin and glucagon secretion, and decrease fat
    absorption in intestines)
  • F cells regulate exocrine function of pancreas
    (secrete pancreatic polypeptide)

77
5. Pancreas Glucagon
  • actions hyperglycemic (increases blood glucose)
  • stimulates formation and release of glucose from
    liver (main target)
  • glycogenolysis - breakdown of glycogen (storage
    form of glucose)
  • gluconeogenesis - formation of glucose from
    noncarbohydrate molecules (e.g., amino acids,
    glycerol, lactic acid)
  • stimulates glycogenolysis in skeletal muscle
  • stimulates triglyceride breakdown in adipose
    tissue (fat mobilization)

78
5. Pancreas Glucagon
  • control
  • secreted in response to low blood sugar, rising
    amino acid levels in blood
  • inhibited by increased blood glucose and by
    somatostatin

79
5. Pancreas Insulin
  • actions hypoglycemic (lowers blood glucose)
  • increases transport of glucose into muscle and
    fat cells (NOTE does not increase uptake by
    brain, liver, or kidney)
  • inhibits breakdown of glycogen and formation of
    glucose from amino acids or fatty acids (inhibits
    glycogenolysis and gluconeogenesis)
  • promotes formation of glycogen (liver, skeletal
    muscles), protein synthesis (muscle), and fat
    synthesis and storage (adipose)

80
5. Pancreas Insulin (Control)
  • stimulated by
  • increased blood glucose
  • increased blood amino acid and fatty acid levels
  • parasympathetic impulses
  • hyperglycemic hormones (GH, glucagon,
    epinephrine, thyroxine, glucocorticoids)
    indirectly result in insulin secretion by
    increasing blood glucose levels
  • inhibited by
  • low blood glucose and by somatostatin
  • sympathetic impulses

Fig. 17.17, p. 637
81
5. Pancreas Insulin - Disorders Diabetes
Mellitus (DM)
  • hyposecretion (or hypoactivity) of insulin
  • body cells not stimulated to take up glucose
  • hyperglycemia (excess blood glucose)
  • very high glucose --gt nausea --gt fight-or-flight
    response --gt secretion of hyperglycemic hormones
    (epi, NE adrenal medulla, glucocorticoids
    adrenal cortex) --gt stimulates gluconeogenesis,
    lipolysis, glycogenolysis --gt adds to already
    high glucose
  • not all sugar reabsorbed from urine --gt glucose
    lost in urine (glucosuria) --gt increased water
    loss --gt excessive urine production (polyuria)
    and excessive thirst (polydipsia)

82
5. Pancreas Insulin - Diabetes Mellitus
  • cells use fats as energy source (due to poor
    glucose uptake)
  • hyperglycemic hormones stimulate fat mobilization
    --gt fats in blood (lipidemia) --gt increase in
    lipid metabolites in blood (ketone bodies, which
    are strong organic acids) --gt decrease blood pH
    (ketoacidosis) and ketone bodies in urine
    (ketonuria)
  • decreased blood pH --gt severe depression of
    nervous system --gt deep breathing --gt diabetic
    coma --gt death
  • polyphagia (excessive hunger) - final sign, due
    to use of fats and proteins as energy sources

83
Type I Diabetes mellitus
  • also called insulin-dependent diabetes (IDDM
    formerly juvenile onset diabetes)
  • onset is sudden, usually before age 15
  • may be due to autoimmune attack of proteins in
    beta cells (see A Closer Look, p. 640-641)
  • result is lack of insulin activity
  • lipidemia (high blood lipid content) and
    increased cholesterol lead to long-term vascular
    problems (arteriosclerosis, strokes, heart
    attacks, renal shutdown, gangrene, blindness)
  • treated with insulin injections or pancreatic
    islet transplant (newer technique)

84
Type II Diabetes Mellitus
  • non-insulin-dependent (NIDDM formerly
    mature-onset diabetes)
  • usually starts after age 40
  • insulin levels are normal or elevated, but
    peripheral tissue become less sensitive to it
  • 25-30 of Americans carry gene that predisposes
    them to NIDDM, more likely in over-weight people
    (90 of cases)
  • adipose cells secrete tumor necrosis factor alpha
    that depresses production of protein needed for
    glucose uptake
  • often controllable with diet and exercise

85
Hyperinsulinism
  • excess of insulin (usually from injection of
    excess)
  • causes hypoglycemia --gt secretion of
    hyperglycemic hormones (to raise blood glucose)
    -? low glucose to brain --gt anxiety, nervousness,
    tremors, weakness --gt eventually, disorientation,
    convulsions, death due to insulin shock
  • treated by providing sugar source

86
6. Gonadal Hormones
  • Female - ovaries
  • produce/secrete estrogens and progesterone
  • estrogens alone --gt development and maintenance
    of ovaries, uterus, secondary sex characteristics
  • estrogens with progesterone --gt breast
    development, uterine cycle

http//www.lab.anhb.uwa.edu.au/mb140/CorePages/Fem
aleRepro/femalerepro.htmFollicles
87
6. Gonadal Hormones
  • Male - testes
  • produce androgens (testosterone) --gt development
    and maintenance of male reproductive system and
    secondary sex characteristics sperm production,
    protein synthesis
  • inhibin - inhibits release of FSH and LH

http//www.usc.edu/hsc/dental/ghisto/rep/c_72.html
88
7. Thymus
  • located in mediastinum
  • function
  • active during childhood and before puberty,
  • after puberty gradually decreases in size and
    becomes fibrous (involution)
  • secretes thymosin (thymic extract containing
    several complementary hormones)
  • action promotes development and maturation of
    lymphocytes
  • gradual decrease in size and secretory abilities
    make the elderly more susceptible to disease

89
General Adaptation Syndrome (GAS)
  • stress response
  • stress any condition that threatens to alter
    homeostasis
  • same general response to a variety of stress
  • major endocrine player is adrenal gland (medulla
    and cortex)
  • three phases
  • alarm
  • resistance
  • exhaustion

90
GAS Alarm Phase
  • immediate response to stress
  • mobilization of energy sources
  • sympathetic division activated results in release
    of epinephrine, NE from adrenal medulla

91
GAS Alarm Phase
  • direct neural and epinephrine effects
  • increased heart rate
  • dilation of pupils
  • changes in circulation (more to skeletal
    cardiac muscle, less to gut)
  • increased respiration
  • increased energy use by cells
  • increased blood glucose
  • decreased digestion and urine production
  • increased perspiration

92
GAS Resistance Phase
  • when stress is present more than a few hours,
    able to cope for weeks to a few months
  • secretion of renin from kidney --gt
    renin-angiotensin pathway --gt aldosterone
    secretion --gt increased Na reabsorption --gt
    increased water retention
  • secretion of ACTH from pituitary
  • increased aldosterone secretion
  • increased glucocorticoid secretion --gt increased
    blood glucose, conservation of glucose by muscle,
    lipids and proteins mobilized as alternative
    energy sources
  • secretion of glucose conservation hormones
    (growth hormone, thyroid hormone, epi) --gt
    conservation of glucose and use of alternatives

93
GAS Exhaustion Phase
  • prolonged stress (more than a few months)
  • homeostatic breakdown due to
  • mineral (electrolyte) imbalances
  • depletion of glucocorticoids
  • exhaustion of lipid reserves (especially with
    starvation)
  • structural or functional damage to organs

94
Adrenal Gland Role in GAS
Fig. 17.15, p. 635
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