Histology of Endocrine SystemMK

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    Lecture by Prof. Marina Kapitonova

    for the year 2 UiTM Dental Students

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    OBJECTIVES:

    1. Define and provide classification of theendocrine glands.

    2. Describe microscopic anatomy of the pituitary as

    the central endocrine gland.

    3. To describe microscopic anatomy of the adrenal

    glands, thyroid and parathyroid glands as

    peripheral endocrine glands.

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    General provisions.

    1. Endocrine system in collaboration with the nervous system, orchestrates

    homeostasis by influencing, coordinating, and integrating the

    physiological functions of the body.2. Whereas the nervous system responds rapidly with a response of short

    duration, the endocrine system responds slowly, and the response is of

    longer duration.

    3. Endocrine glands are responsible for the synthesis and secretion of

    chemical messengers known as hormones which are disseminatedthroughout the body by bloodstream where they act on specific target

    organs. Therefore endocrine glands possess an extensive vascular

    supply that is particularly rich in fenestrated capillaries. They have no

    excretory ducts as they discharge their product directly in blood.

    4. Endocrine glands function by a regulatory system known as negative

    feedback in which production of a hormone affects a target organ to

    initiate a response that eventually reduces secretion of that hormone.

    5. The endocrine system consists of several glands, composed of islands

    of secretory cells of epithelial origin,as well as ofisolated groups of cells

    within certain organs, and individual cells scattered among parenchymal

    cells of the body.

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    Classification of the Endocrine System1.Endocrine glands (pituitary, epiphysis, thyroid gland,

    parathyroid glands, adrenal glands).

    2. Mixed glands (testes, ovaries, pancreas).3. Paracrine system (APUD).

    Endocrine glands:

    1. Central (pituitary hypothalamo-hypophyseal system;pineal gland epithalamo-epiphyseal system).

    2. Peripheral (thyroid, parathyroid and adrenal glands, sex

    glands, pancreas).

    Peripheral endocrine glands:1.Pituitary-dependent (thyroid gland, adrenal cortex, sex

    glands).

    2.Pituitary independent (adrenal medulla, parathyroid

    glands, pancreas).

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    Pituitary Glandand its hormones

    The hypophysis is a

    master endocrine gland

    connected to the hypothalamus at

    the base of the brain, with which is

    has important anatomic andfunctional relationship and formes

    hypothalamo-hypophyseal system

    providing the highest level of control

    of the endocrine functions.

    Similar relations exist

    between pineal gland andepithalamus forming epithalamo-

    epiphyseal system.

    Other endocrine glands

    (thyroid, parathyroid, adrenal

    glands) are considered to beperipheral endocrine glands (purely

    endocrine ones).

    Pancreas, ovaries, testes

    combine functions of the endocrine

    and exocrine glands.

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    cavity of the

    3rd ventricle

    pituitary

    stalk

    median

    eminence

    mammil

    bodyoptic chiasm

    pars tuberalis

    diaphragm

    sella

    anterior pituitary

    pars

    intermediafibrocollagenous

    setum with cysts

    pituitary

    fossa

    sella

    turcica

    dura

    mater

    sphenoid bone

    post.

    pitui-

    tary

    neural

    lobe

    Scheme of pituitary

    The pituitary or

    hypophysis is dividedinto adenohypophysis

    and neurohypophysis

    having different

    embryonic origin.

    Adenohypophysis

    includes pars distalis (orpars anterior), pars

    tuberalis and pars

    intermedia.

    Neurohypophysis is

    formed by the posteriorlobe of the gland.

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    The pituitary is suspended from the hypothalamus (H) by the

    infundibulum which is composed of ther neural portion (infundibular stem,

    IS) and the surrounding pars tuberalis (PT). The 3rd

    ventricle of the brain iscontinuous with the infundibular recess (IR). Pars anterior (PA) is the

    largest portion of the pituitary which is glandular and secretes numerous

    hormones. Pars nervosa (PN) does not manufacture hormones but stores

    and releases them. Pars intermedia (PI) is located between pars anterior

    and pars nervosa, it frequently presents intraglandular cleft (colloid-filled

    cyst) which is a remnant ofRathkes pouch.

    Pituitary gland,H & E

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    Anterior lobe of the hypophysis, toluidine blue staining

    Endocrine cells (E)

    of the

    adenohypophysis

    are arranged in

    groups andsurrounded by

    capillaries (C). The

    capillaries are wide,

    endothelially linedvessels known as

    sinusoids.

    E

    E

    E

    C

    C

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    Lobus anterior (or pars distalis) comprises 80% of the pituitary,while pars intermedia in humans is less developed.

    Pars distalis is composed of large cords of cells that branch and

    anastomose with each other. Traditionally cells of the anterior lobe of the

    pituitary have been classified into three types: acidophils (A), (cytoplasm

    staining by acidic dyes), basophils (B) (cytoplasm staining by basic dyesand PAS-method) and chromophobes (CO) which do not stain.

    Pars distalis of the

    pituitary, H & E

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    The chromophobes do not take up the stain well and only their

    nuclei are demonstrable. They make about 50% of cells of pars distalis.

    These cells are small, therefore chromophobes are easily recognizable since

    their nuclei appear to be clumped together. They represent either non-

    specific stem cells or partially degranulated chromophils.

    Pars Distalis of the Pituitary, H & E.

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    Adenohypophysis,

    PAS-Orage G.

    h

    On the picture acidophils (A) are stained

    bright, basophils (B) are stained dark

    while chromophobes (C) are not

    stained.

    It is now customary to classify cells according to their hormone content which

    is demonstrable by modern immunohistochemocal methods of staing usingantibodies to each hormone type. It was shown that acidophils are cells secreteing

    growth hormone and prolactine (i.e. somatotrophs and lactotrophs), and basophils

    (PAS+) are gonadotrophs, thyrotrophs or corticotrophs. Basophils stain well with

    hematoxylin and PAS which detect glycosil groups, as luteinizing hormone (LH),

    follicle stimulating hormone (FSG) and thyrocyte stimulating hormone (TSH) are

    glycoproteins, and the ACTH precursor protein is glycosylated.

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    Most of the chromophil cells in the pituitary (40%) are

    acydophils, and among them the majority are somatotrophs

    (arrows). Besides the granules, there are mant parallelcysterns of the RER in the cytoplasm. In the malignant cells

    thick bundles of the intermediate filaments may be discovered.

    Most of the granules measure 350-450 nm in diameter, though

    the range is between 300 and 600 nm.

    Anterior lobe of the

    pituitary,

    immunohistoche-mical staining for

    somatotropin.

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    Lactotrophs make up to 25% of the anterior pituitary. While some are

    rounded and polygonal (arrows), most are compressed by adjacent cells intonarrow angular profiles). They increase in size and number during pregnancy and

    lactation. Ultrastructurally they have a prominent Golgi compared to all other

    anterior pituitary cells and their granules measure 200-350 nm in diameter.

    Interesingly, exocytosis may be seen at their lateral borders (misplaced

    exocytosis) as well as in the usual site adjacent to capillary basement membrane.

    This feature can be used in diagnostic assessments as it is limited to lactotroph-derived tumors.

    Anterior pituitary,

    immunohistochemical

    staining for prolactin.

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    Accounting for 15-20% of the anterior pituitary, corticotrophs (arrow)

    are large and polygonal in shape, as shown in this micrograph stained to

    show ACTH by immunoperoxidase technique. Many corticotrophs possess

    an unstained perinuclear vacuole called the enigmatic body, which isderived from secondary lysosomes. Granules in corticotrophs are large

    band typically measure 250-700 nm in diameter. Large perinuclear bundles

    of intermediate cytokeratin filaments are prominent ultrastructurally and

    these become even more prominen in glucocorticoid excess, when they are

    visible under the light microscope as pink-staining inclusions (Crookes

    hyalin).

    Anterior

    pituitary,

    immuno-histoche-

    mical

    staining for

    ACTH.

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    Constituting around 10% of anterior pituitary cells, gonadotrophs

    (arrow) are scattered as single cells or small groups throughout the gland as

    seen in this section stained for the beta-subunit of FSG by

    immunoperoxidease technique. Both FSH and LH may be evident within the

    same cell. Ultrastructurally the granules are 150-400 njm in diameter.Following ablation of the ovaries or testes, gonadotrophs develop extensive

    cytoplasmic vacuolation. This is due to dilation of the endoplasmatic

    reticulum by stored product and caused by the loss of feedback inhibition by

    gonadal steroids. Such cells, large rounded and vacuolated on light

    microscopy, are called castration cells.

    Anterior pituitary,

    immunohisto-

    chemical staining

    for FSH.

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    It is also possible to distinguish cells of the anterior pituitary by elecron

    microscopy. The electron microphotograph reveals the presence of the dence

    core granules in the cytoplasms of adonocytes. Chromophobes fail to stain

    because they contain very few granules, and may be lactotrophs, somatotrophs,gonadotrophs, thyrotrophs or corticotrophs by nature.

    G

    G

    Anterior lobe of the

    pituitary, E,

    12,000

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    Posterior pituitary is composed of axons which originate from cells

    in the hypothalamus and possess numerous neurosecretory granules

    containing either oxytocin or vasopressin together with a carrier proteintermed neurophysin, and ATP. Where axons are adjacent to capillaries

    they form fusiform swellings filled with neurosecretory granules (Hering

    bodies). The posterior pituitary also contains specialized stellate-shaped

    glial cells called pituicytes. In the micrograph the axons are seen a pale

    fibrillary background in which the nuclei of pituicytes (P) and small

    capillary vessels are present.

    Posterior pituitary,

    H & E.

    P

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    Hypothalamic control of anterior pituitary hormone production.

    Hypothalamic

    neurons secrete

    releasing/inhibiting

    factors in response

    to chemoreceptiveand neural inputs.

    These hormones

    diffuse into

    capillaries at the

    median eminenceand are carried to

    the anterior pituitary

    in the portal vessels.

    Astrocyte

    foot processes

    surrounding the

    cappilaries form part

    of their diffusion

    barrier.

    capillary

    astrocyte

    anteriorpituitarycells

    astrocytefootprocess

    endothelial

    cell

    basementmembrane

    portal vessel

    capillaryat median

    eminence

    releasing/Inhibitingfactor

    hypothalamicneuron

    neuralsynapse

    Summary of Histology of Pituitary and Hypophysis

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    Loca-tion

    Gene-ral celltype

    Spe-cificcelltype

    Hor-mone

    Targettissue/organ

    Natureof hor-mone

    Gra-nulesize

    Stain-ing

    Func-tions

    parsdista-lis ofthepitui-

    tary

    acido-phils

    soma-to-trophs

    soma-totro-phin orgrowthhormo-

    ne (GH)

    espe-ciallymuscleandbone

    pro-tein

    300-400nm

    Orange

    G

    stimulates

    growth,

    promotes

    protein

    synthesis in

    bones and

    muscles,

    influences

    carbo-

    hydrate and

    lipid meta-

    bolism.

    acidophil

    mam-mo-troph

    prolac-tine

    breast pro-tein

    550-700

    nm

    Orange

    G

    initiates &

    regulates

    lactation,

    promotes

    mammary

    develop-ment

    Summary of Histology of Pituitary and Hypophysis

    Loca Gene Spe Hor Target Nature Gra Stain Func

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    Loca-tion

    Gene-ral celltype

    Spe-cific celltype

    Hor-mone

    Targettissue/organ

    Natureof hor-mone

    Gra-nulesize

    Stain-ing

    Func-tions

    parsdista

    -lisofthepitui-tary

    basophil

    gona-do-

    trophs

    folli-culo-trophs

    follicle-

    stimu-latinghor-mone

    ovary &testis

    glyco-pro-

    tein

    150-200

    nm

    PAS stimulates

    develop-

    ment offollicles in

    the ovary &

    semini-

    ferous

    tubules in

    the testes

    basophil

    luteo-trophs

    lutei-nizinghormone

    ovary(corpusluteum)

    Glyco-pro-tein

    150-200

    nm

    PAS stimulates

    corpus

    luteum

    develop-

    ment &progesteron

    secretion:

    necessary

    for ovula-

    tion and

    estrogensecretion

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    Loca-tion

    Gene-ral celltype

    Spe-cificcelltype

    Hor-

    mone

    Tar-getorgan

    Natureof hor-mone

    Gra-nulesize

    Stain-ing

    Func-tions

    parsdista-lis ofthepitui-tary

    baso-phil gona-do-troph

    intersti-cial cellstimula-ting hor-mone,probablysame asLH

    testis glyco-pro-tein

    150-200nm

    PAS &

    alde-

    hyde-

    fuchsinPAS

    stimu-latesLeidigcells toproducetesto-sterone

    baso-phil

    corti-co-troph

    adreno-cortico-tropin

    (ACTH)

    adre-nalcortex

    Poly-pep-tide

    200-250

    nm

    PAS stimulatessynthesis

    of adreno-

    corticalsteroid

    hormones

    baso-phil

    thyro-troph

    thyroid-stimula-

    ting hor-mone-TSH

    thy-roid

    glycoprotein

    130-150

    nm

    controls

    thyroxine

    production

    & release

    Loca Gene Spe Hor Tar get Natu Gra Stain Func

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    Loca-tion

    Gene-ral

    Spe-cific

    Hor-mone

    Tar-getorgan

    Natu-re ofhor-mone

    Gra-nulesize

    Stain-ing

    Func-tions

    parsinter-media

    baso-phil mela-no-troph

    APUD

    melano-cyte sti-mulatinghormone(MSH)

    skin ofloweranimals

    poly-pep-tide

    200-300nm

    PASstimulatesmelano-

    cyte

    expansion

    pars

    nervo-sa ofthepitui-tary

    neuro

    -glia

    pitui-

    cyte

    none storage and

    release ofneuro-

    hormones

    of hypo-

    thalamus:

    vasopressin,

    oxytocin

    hypo-thalamus

    neuro-secre-toryneu-

    rons

    neurons

    in para-

    ventri-

    cular

    nuclei

    oxy-tocin

    smoothmuscle,especi-ally

    uterus

    poly-pep-tide

    100-300nm

    Gomori stimulates

    contraction

    of the ute-

    rine wall

    duringparturition.

    L G S H T t N t G St i F

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    Loca-tion

    Gene-ral

    Spe-cific

    Hor-mone

    Targetorgan

    Natureof hor-mone

    Gra-nulesize

    Stain-ing

    Func-tions

    hypo-

    thalamus

    neuro-secre-toryneu-rons

    neu-

    rons insupra-optical-nuclei

    vaso

    pres-sin(anti-diure-tichor-mone- ADH

    renal

    collect-ingtubules,arterio-les

    poly-

    pep-tide

    100-

    300nm

    Gomori increases

    water

    absorption

    of renal

    collecting

    tubules,

    constricts

    arterioles toincease

    pressure

    neuro-secre-toryneu-rons

    neu-rons in

    tuberalnuclei

    six re-

    leasing

    factors

    (RF);

    two

    known

    inhibi-

    tingfactors

    parsdistalis

    parsdistalis

    pep-tide

    pep-tide

    - causesrelease of

    the anterior

    pituitary

    hormones;

    inhibits

    release of

    the anterior

    pituitaryhormones

    3rd tentorium

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    Diagram shows the

    location of the pineal gland.

    Output of pineal melatonin

    is modulated by light

    through nervous pathwayswhich input as sympathetic

    innervation to the gland. It is

    also thought to influence

    gonadal activity

    (suppression). The

    parenchyma is composed ofpinealocytes and interstitial

    cells. Pinealocytes are

    resposible for secretion of

    serotonin and melatonin,

    while the interstisial cells

    are believed to astroglia-likecells.

    Pineal Gland

    light

    eye

    nervus

    opticus

    central

    sympathetic

    pathways

    superior cervicalganglion

    cerebellum

    n.suprachi-

    asmaticus

    pituitary

    gland

    optic

    chiasm

    pineal

    gland

    3rd

    ventricle

    tentorium

    cerebellicorpus

    callosum

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    Thyroid possesses three features of special significance:

    1) it is unique among the endocrine glands in that it manufactures hormones, stores

    them extracellularly and releases for use as required,

    2) it is the only endocrine gland that depends on the external environment for raw

    materials of its hormones,

    3) it possesses one of the richest blood flow compared to adrenal and other glands,

    4) thyroid hormones are the only among amino-acid-derived hormones which being

    lipid-soluble, diffuse through the cell membrane and binds to intracellular hormone

    receptor proteins in the target cells (other amino acid-derived hormones receptorsare present in the cell membrane of the target cells).

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    I. General Morphology

    1. The thyroid gland consists of right and left lobes

    connected across the middle line by a narrowportion, the isthmus (and sometime pyramidal lobe).

    2. Its weight is somewhat variable, but is usuallyabout 30 grams.

    3. It is slightly heavier in the female, in whom it

    becomes enlarged during menstruation andpregnancy.

    4. Parenchyma of thyroid gland: follicles +

    interfollicular clusters of calcitoninocytes.

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    Human Thyroid Gland, H. & E., 162 x.

    Stroma: the inner, true, connective tissue (CT) capsule sends in septa to

    partially enclose lobules separated by a loose CT, with many blood vessels.

    Follicles are the structural units of the thyroid gland. Note variations in shape

    (rounded or tubular) and size (0.05 to 0.5 mm in diameter). Close packingwith a thin reticular network between adjacent follicles.

    colloid

    follicles

    bloodvessels

    100 m

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    Lined by basophilic cuboidal follicular cells, varying in height fromsquamous to low columnar as a simple epithelium on a basal lamina,outside which is an extensive plexus of blood capillaries, and reticular

    fibres and fibroblasts. Follicular cells are polarized with respect to thefollicle lumen. Nucleus is placed centrally or basally. Colloid is found in the

    lumen of follicles. It is variably acidophil or basophil, and often shrunken

    and showing knife chatters.

    colloid

    follicle

    Human Thyroid Gland, H. & E.

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    Thyroid follicles:1. In man they vary markedly between 0.02 and 0.9 mm in diameter.

    2. Larger follicles filled with colloid have a squamous or cuboidalepithelium.

    3. Glands with follicles that have predominantly squamous epithelial

    cells are considered to be hypoactive.

    4. When the gland is stimulated to synthesize thyroid hormone, thefollicular epithelial cells become columnar and the amount of colloid

    is reduced.

    5. Each follicle can store several weeks supply of hormone within

    colloid.

    6. A gland has several million follicles.7. Chemical composition of colloid is a glycoprotein-iodine

    complex (thyroglobulin). The follicles release about 100 mg of

    hormone daily. Of the several iodinated compounds found in the

    gland the 3, 5, 3-triiodothyronine is hormonally the most active.

    Human Thyroid Gland A. H. & E.; B. periodic acid-Schiff and hematoxylin.

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    In B, the colloid is specifically stained red with the periodic acid-

    Schiff method because of the chemical composition of colloid, which

    is a glyco-protein-iodine complex (thyroglobulin).

    Human Thyroid Gland A. H. & E.; B. periodic acid Schiff and hematoxylin.

    In A, the colloid in the lumen of the follicle is not stained.20 m

    A B

    Follicles

    Thyroglobulin

    Follicle

    cell nuclei

    Thyroglobulin

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    Thyroid Physiology:

    Follicular cells:

    (a) Are stimulated by pituitary thyrotrophichormone (TSH) to produce and release twoiodinated amino-acid hormones - tetraiodo-

    thyronine (thyroxine/T4) and 3,5,3-triiodo-L-thyronine(T3),

    (b) which are stored in the colloid, as component

    amino acids of the glycoprotein - thyroglobulin.

    (c) The hormones accelerate general and

    specific metabolic processes of the body.

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    (d) Electron radioautography has shown the sites in the

    sequence of hormone production by the follicular cells:

    i. Iodide concentration - basal part of the follicular cell.

    ii. Iodide oxidation - throughout the cell.

    iii. (ii) Synthesis of thyroglobulin - basal cell, granular ER, Golgi body, by

    vesicle to the lumen.

    iv. In the luminal thyroglobulin, tyrosine residues are iodinated, then pairs

    condense.

    v. Cellular retrieval of thyroglobulin from colloid storage cell's apical

    region by endocytosis.vi. Transport to lysosomes, where cathepsins degrade the large modified

    molecule.

    vii. Release of freed iodothyronines - out of the base of the cells into the

    blood.

    viii. Binding to intracellular proteins after entering cytoplasm andslow use over a period of several days to weeks (both T3 and T4bind to nuclear thyroid hormone receptor proteins, but T3 binds with amuch greater affinity than does T4, which accounts for the greaterbiological activity of T3).

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    Diagram of the synthesis and iodination of thyroglobulin (A) and release of thyroid hormone

    (B).

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    Biological Effects of Triiodothyronine and Thyroxine.

    1) Normal thyroid function is essential for the normal growth, development, and

    tissue metabolism of the body.

    2) T3 and T4: stimulate transcription of many genes

    that encode various types of proteins, resulting in a

    generalized increase in cellular metabolism that may

    be as great as twice resting rate;

    a) stimulate carbohydrate metabolism,

    b) decrease synthesis of cholesterol, phospholipids,

    and triglycerides but increase synthesis of fattyacids and the uptake of various vitamins,

    c) T3 and T4 also increase the growth rate in the

    young, facilitate mental processes, and stimulate

    endocrine gland activity.

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    CLINICAL CORRELATES:

    Increased thyroid hormone production:

    a) decreases body weight,

    b) increases heart rate,

    c) increases metabolism, respiration,

    muscle function, and appetite.

    d) hormone production increases from 5 to 15times normal.

    E i t f th id h

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    Excessive amounts of thyroid hormone(hyperthyroidism) cause:

    a) muscle tremor and weakness,

    b) tiredness,

    c) impotence in men,

    d) frequent menstrual bleeding in women.

    e) excessive appetite and thirst,

    f) weight loss,

    g) rapid respiration, sweating, heat intolerance (due to an increase

    d basal metabolic rate),

    h) increase in heart rate (tachycardia)

    i) emotional disturbance and nervousness

    k) bulging (protrusion) of the eyes (exophthalmos) - occurs due to

    an increase in orbital support tissue.

    l) increases of the size of the thyroid gland two to three times above

    normal

    Th id Gl d H l i Diff

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    Thyroid Gland, Hyperplasia, Diffuse

    In thyroxic hyperplasia a number of follicular cells increases, papillary folds

    of acinar epithelium develop. In addition each epithelial cell is large

    columnar and the edges of colloid are scalloped, indicating active removalof stored colloid for processing into thyroxine.

    colloid in lumen of follicle papillary infoldings

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    CLINICAL CORRELATIONS:

    Overactivity of the thyroid(hyperthyroidism) may be due to a numberof factors.

    In Graves disease, the thyroid isoveractive even with low levels of THS, dueto an immunologic disturbance in which an

    immunoglobulin has an effect similar tothat of TSH (autoimmune IgG antibodiesbind to TSH receptors which stimulatethyroid follicular cells).

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    Deficiency of thyroid hormone:

    a) from the time of birth results in:

    1a) a dwarf child who is mentally retarded (cretinism).

    2a) slow heart rate, muscular weakness, and

    gastrointestinal disturbances.

    Thyroid hormone given to infants at an early stage of

    cretinism can alleviate the symptoms.

    b) i d lt

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    Patients with severe hypothyroidism may develop myxedema, which ischaracterized by bagginess under the eyes and swollen face that is due to

    nonpitting edema of the skin, infiltration of excess glycosaminoglycans, and

    proteoglycans into the extracellular matix.

    b) in adults:

    1b) mental slowing,

    2b) cold intolerance,

    3b) reflex changes,4b) skin changes

    5b) fatigue, sleeping for up to 16 hours per day,

    6b) muscular sluggishness,

    7b) slowed heart rate, decreased cardiac output and blood volume

    8b) failure of body functions,

    9b) constipation,

    10b) loss of hair growth.

    PARAFOLLICULAR CELLS

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    PARAFOLLICULAR CELLS

    OF THE THYROID GLAND

    In thyroid between the follicular cells and the basal lamina (BL), and sometimes

    outside the BLs, lie occasional C cells (clear/parafollicular cells), having no directaccess to the lumen, and no colloid droplets, but with small argyrophil, secretory

    granules.

    Histophysiology of C-cells:(a) they are APUD cells of neural crest origin,

    (b) and produce the polypeptide calcitoninfor the reduction of highplasma Ca2+ and phosphate levels by inhibiting bone resorption

    by osteoclasts and decreasing calcium and phosphate

    reabsorbtion by renal tubules. It may increase the rate of osteoidmineralization.

    (c) although diffuse, in sum they form a gland antagonistic to the

    action of the parathyroids.

    (d) the secretion of calcitonin results from elevation of blood calcium

    concentration above normal levels.

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    PARAFOLLICULAR CELLS (C CELLS)

    Thyroid gland, H. & E.

    Parafollicular cells are located between follicular cells

    or in the interstitial connective tissue.

    C

    C

    C

    G l M h l d Mi t t f C ll

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    General Morphology and Microstructure of C-cells.

    1. Although C-cells are 2 to 3 times larger than follicular cells, they

    account for only about 0.1% of the epithelium.

    2. Parafollicular cells may be found intimately associated with thyroid

    follicles or as isolated or interstitial clusters of cells (the latter location,

    which is less common for human thyroid, explains the archaic name

    parafollicular cells). They are not readily found in routine thicker

    sections of the thyroid gland. The photomicrographs above are from1.5 m plastic sections.

    3. Although parafollicular cells appear, at the light microscopic level, to

    be in intimate contact with thyroid colloid, they are, in fact, separated

    from colloid by thin intervening processes of adjacent thyroid follicular

    cells.

    4. Ultrastructurally they contain dense-core neurosecretory granules that

    are characteristic of neuroendocrine cells.

    PARAFOLLICULAR CELLS (C CELLS)

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    H. & E.,

    A. 119 x;

    B. & C. 169 x.

    PARAFOLLICULAR CELLS (C CELLS)Thyroid gland

    C

    B

    A

    A 100 mB & C 50 m

    Parafollicular

    cells

    Thyroid

    follicles

    Parathyroid

    gland

    Thyroid

    follicular cells

    Colloid

    parafollicular

    cells

    Follicle filled

    with colloid

    Parafollicularcells

    Mast cells

    Interstitial

    aggregation of

    parafollicular

    cells

    Parathyroid gland Human H & E

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    Parathyroid gland, Human, H. & E.

    Stroma: Each of the four (may range from 2 to 12) rounded or ovoid bodies has a

    fine connective tissue capsule and delicate, incomplete septa which divide the glandin lobules. . These septa carry vessels, nerves and many fat cells.

    Parenchyma: supported on fine reticular fibres are many fenestrated blood capillariesand sheets and cords or plates of chief cells (small, 7-10 m diameter; some dark,

    some light: contain glycogen, lipofuscin pigment, and argyrophil secretory granules;

    form occasional small follicles.) and oxyphil cells (larger, acidophilic, and often occur in

    clumps; no secretory granules). The most abundant type is the chief (or principal) cell,which is functionall im ortant.

    A

    C

    C

    O

    Adherent to the true

    capsule of the thyroid,

    the small parathyroid

    glands (4 to 5 mm in

    diameter) and are

    usually found on the

    posterior surface of the

    thyroid gland.

    P h id H H & E

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    Parathyroid, Human, H. & E.

    Chief cells: with prominent nucleus, round and centrally located, and cytoplasm thatstains variably and may be light or dark depending upon its secretory activity.

    The second type, oxyphilic (acidophilic or eosinophilic) cells, occurs in fewer numbers

    in small clumps or nests among chief cells. Larger than chief cells. Oxyphilic cells

    usually arise after puberty and increase in number beyond the age of 40 but their

    specific function is unknown. May be derived from chief cells.

    Oxyphil cells: occurs in small clumps and in fewer numbers. These cells usually

    have small densely staining heterochromatin and an oxyphilic cytoplasm whoseperimeter is usually well defined.

    C

    C

    O

    3 Functions

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    (d) unlike most other endocrine glands, no specific pituitary trophic

    hormone is involved in its control.

    3.Functions

    (a) Secretory granules of chief cells are the polypeptide hormone,

    parathormone/PTH, which is important in calcium and phosphatemetabolism acting mainly on bone and the kidney:

    1a) it is released in response to low blood Ca2+,

    2a) acts on osteoclasts and macrophages to increase boneresorption,

    3a) it also removes calcium phosphate directly from bone matrix, and,

    via intermediary factors, from osteoblasts;.

    (b) in the kidney:

    1b) PTH: promotes the tubular reabsorption ofcalcium

    2b) inhibits the renal tubular reabsorption of phosphate - aphosphaturic action;

    (c) promotes conversion of 25-hydroxyvitamin D to 1,25 -dihydroxyvitamin D (this metabolite increases calcium absorbtion by

    the gut);

    Clinical Correlates:

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    Parathyroid glands are essential for life whereas calcitonin of

    the thyroid appears to provide a complementary mechanism

    for fine adjustment of blood calcium level and is not essentialfor life.

    In the absence of parathyroid hormone, there is a pronounced

    decrease in blood calcium resulting in tetany, abnormal

    twitching, the intense, involuntary spasm of skeletal muscle.caused by changes in excitability at the neuromuscular

    junction, and death.

    Dietary addition of calcium and especially administration of

    parathyroid hormone relieves the abnormal spasms,

    preventing death of the organism.Abnormal levels of calcium may result in abnormal deposition

    of calcium in the kidneys and muscle. Abnormally increased

    blood levels of calcium occur at the expense of bone, which

    may fracture as a result.

    Clinical Correlates:

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    Adrenal Gland

    Cortex: Zona glomerulosa (narrow

    subcapsular zone of cortex) secretesmineralocorticoids, mainly aldosterone.

    Zona fasciculata (broad, yellow mid-zone of

    cortex) secretes glucocorticoids, mainly cortisol

    and corticosterone.

    Zona reticularis (narrow inner zone of

    cortex) secretes mainly androgenic steroids.

    Adrenal medulla (central, enclosed by

    cortex, brown) is neuroendocrine and secretes

    epinephrine and norepinephrine

    (noradrenaline).

    cortexmedulla

    z.reticularis

    z.fasciculata

    z.glomerulosa

    capsule

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    The zona glomerulosa is composed of small compact cells (C)

    arranged in clumps and separated by stroma composed

    largely of thin-walled capillaries. The cells contain scanty lipid

    droplets associated with well developed SER and

    comparatively little RER.

    Adrenal

    Cortex,

    H & E.

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    Zona fasciculata contains cells arranged in vertical

    columns, which are usually 2-3 cells wide, the

    columns being separated by capillaries (Cap).

    Adrenal Cortex, H & E.

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    The inner zona reticularis produces androgenic steroids and some glucocorticoids, butnormally only in small amounts. The inner zone of adrenal cortex is thinner than the zonafasciculata, but thicker than the zona glomerulosa. It is composed of cells with eosinophyliccytoplasm arranged in an anastomosing network of clumps and columns with a capillarynetwork closely apposed to the cell membranes. A characteristic feature of this layer whenstained with H & E is the present of brown pigment (lipofuscin). To the naked eye the layer

    appears pale brown, whereas the zona fasciculata is bright yellow.

    Adrenal Cortex,

    Zona Reticularis.H & E.

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    Because of their high catecholamine content, adrenal medullary cellsdevelop an intensive brown color when exposed to air or to a strongoxidizing agent, such as potassium dichromate, due to the formation ofbrown pigment when the amines are oxydized. This is the basis of theirantiquated name chromaffincells.Adrenal medullary cells (E- and N-cells) show their large nuclei and finelygranular cytoplasm.

    Adrenal

    Medulla,

    H & E

    Adrenal Medulla TEM x20 000

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    Large dense-core

    granules

    corresponding tonorepinephrine (N)

    and epinephrine (E)

    granules.

    Adrenal Medulla, TEM, x20,000