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Lecture : HPA Histology By : Rakhshindah Qureshi Email : [email protected] OFFICE : # 1123 Learning Objectives : • 1.Describe the subdivisions and structure of pituitary gland (hypophysis ) . • 2.Describe the staining characteristics and functions of the subtypes of cells in the pars distalis . •...

Lecture : HPA Histology By : Rakhshindah Qureshi Email : [email protected] OFFICE : # 1123 Learning Objectives : • 1.Describe the subdivisions and structure of pituitary gland (hypophysis ) . • 2.Describe the staining characteristics and functions of the subtypes of cells in the pars distalis . • 3.Describe the histology of pars intermedia . • 4.Describe the histology and functions of pars tuberalis . • 5.Describe the histology of neurohypophysis . • 6. Explain the functions & origins of the major cell types of the neurohypophysis . • 7.Describe the secretions stored in neurohypophysis . • 8. Explain the blood flow through the hypophysis . Reference : AT Lecture Notes Color atlas of Histology by Gartner & Hiatt 8th edition Endocrine Glands Histology • Endocrine glands are composed of islands of secretory epithelial cells with intervening connective tissue , rich in blood and lymphatic capillaries . • The secretory cells discharge hormones into the interstitial spaces, and it is rapidly absorbed into the circulatory system . • Cells of endocrine glands have prominent nuclei , abundant mitochondria , endoplasmic reticulum , Golgi bodies and secretory vesicles . Endocrine Glands Histology • The endocrine system can be divided into 3 parts : • 1. The major endocrine organs , where the major or sole function of the organ is synthesis , storage and secretion of hormones e.g thyroid and adrenal glands . • 2. Endocrine components within other solid organs , e.g the endocrine components of pancreas , ovary , testis , kidneys , in the form of clusters of endocrine cells within other tissues . • 3. The diffuse endocrine system , scattered individual cells or small clumps of cells usually within an extensive epithelium e.g GI & Respiratory tracts . The major function of these cells is paracrine ( i.e., acting on adjacent non endocrine cells , rather than entering the blood stream and producing systemic effects ) Endocrine Glands Histology • The nature of secretory vesicles varies according to the hormone secreted . • There are 4 main groups of chemicals which act as hormones : • 1. Protein and glycoprotein molecules e.g insulin , growth hormone , parathyroid hormone (PTH) • 2. Small peptide molecules e.g vasopressin , products of enteroendocrine cells . • 3. Amino acid derivatives e.g thyroxine , adrenaline (epinephrine) & noradrenaline (norepinephrine) • 4. Steroids derived from cholesterol e.g adrenal cortical hormones , ovarian and testicular hormones PITUITARY GLAND • Also known as the hypophysis , is a small bean shaped gland , at the base of the brain beneath the 3rd ventricle , in a bony cavity in the base of the skull (sella turcica) . • The gland is divided into anterior and posterior parts which have different embryological origins , functions and control mechanisms . • The secretion of all major pituitary hormones is controlled by hypothalamus , which itself is under the influence of nervous stimuli from higher centers in the brain . • Control is mainly by feedback from the levels of circulating hormones produced by pituitary - dependent endocrine tissues . PITUITARY GLAND • Hormones produced by the pituitary gland are important in regulating growth , reproduction and metabolism . • The pituitary hormones fall into 2 functional groups : • 1. Hormones which act directly on non- endocrine tissues : growth hormone (GH) , prolactin , antidiuretic hormone (ADH) , oxytocin and melanocyte stimulating hormone (MSH) . • 2. Hormones which modulate the secretory activity of other endocrine glands ( trophic hormones) : thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH) and the gonadotrophic hormones, follicle stimulating hormone (FSH) and luteinizing hormone(LH) . • Thyroid gland , adrenal cortex and gonads are pituitary – dependent endocrine glands . ANTERIOR PITUITARY GLAND (Adenohypophysis ) • The anterior pituitary arises as an epithelial outgrowth from the roof of the primitive oral cavity known as the Rathke’s pouch. The anterior pituitary is called Adenohypophysis . • The remnants of Rathke’s pouch divide the anterior pituitary into 3 parts : • 1. Pars distalis • 2. Pars tuberalis • 3. Pars intermedia PITUITARY GLAND • Posterior pituitary • • • • (Neurohypophysis), grows as an evagination from the floor of the brain ( the diencephalon) and maintains a stalk like attachment to the brain . Subdivisions of neurohypophysis include : Pars nervosa Infundibulum Median eminence ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS DISTALIS : • ~75% of the adenohypophysis and has a thin fibrous capsule . • The main components are the cords of endocrine cells interspersed with fenestrated capillaries and supporting reticular connective tissue . • Two different types of cells with different staining affinities are seen : • 1. Chromophils , which can either be Acidophils or Basophils . • 2. Chromophobes . ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS DISTALIS : • CHROMOPHILS : • ACIDOPHILS : make up ~ 30-40% of the cells in pars distalis • 1. SOMATOTROPHS : or somatotropic cells secrete growth hormone (somatotropin) • 2. LACTOTROPHS : or lactotropic cells secrete prolactin • BASOPHILS : comprise ~10-25% of the cells in pars distalis . • 1. CORTICOTROPHS : secrete adrenocorticotropic hormone (ACTH) , with target cells in the adrenal cortex • 2.GONADOTROPHS : secrete follicle stimulating hormone (FSH) & luteinizing hormone (LH) with target cells in the gonads . • 3. THYROTROPHS : secrete thyroid stimulating hormone ( TSH) with target cells in the thyroid gland ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS DISTALIS : • CHROMOPHOBES : stain weakly , with a few secretory granules , represent a heterogeneous group of cells including stem cells & undifferentiated progenitor cells . • Chromophobes comprise ~45-60% of the cells in pars distalis . ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS DISTALIS : • • • Each type of cell in the pars distalis makes one kind of a hormone, except : 1. Gonadotrophs : secrete 2 different glycoproteins , follicle stimulating hormone (FSH) and luteinizing hormone (LH) . 2. Corticotrophs : secrete adrenocortical trophic hormone (ACTH) and βlipoprotein (β-LPH) . ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS TUBERALIS : • Is a smaller funnel shaped region surrounding the infundibulum of the neurohypophysis . • Most of the cells of pars tuberalis ANTERIOR PITUITARY GLAND (Adenohypophysis ) • PARS INTERMEDIA : • A narrow zone lying between pars distalis and the pars nervosa . • The pars intermedia contains basophils (corticotrophs) , chromophobes and small colloid filled cysts derived from embryonic hypophyseal pouch . • Best developed and active during fetal life. • Corticotrophs of Pars intermedia secrete smaller peptide hormones , including melanocyte stimulating hormone (MSH) which increases the activity of melanocytes • It also secretes γ- LPH and βendorphin • Overall functional significance of pars intermedia remains uncertain . ULTRASTRUCTURE OF THE ANTERIOR PITUITARY • These cells are round to polygonal in shape with a prominent nucleus that has one or more nucleoli . • These cells synthesize and secrete protein hormone >> have a prominent Golgi complex, many mitochondria , an extensive rough endoplasmic reticulum and secretory granules (vesicles) . • Secretory vesicles scattered in the cytoplasm or near the cell surface discharge by exocytosis close to thin walled and highly permeable fenestrated capillaries . CONTROL OF HORMONE SECRETION IN ANTERIOR PITUITARY • The activities of the cells of anterior pituitary are controlled primarily by specific hypothalamic releasing hormones (peptides) secreted by small neurons near the 3rd ventricle , released from the axons near the median eminence and transported by capillaries of the portal system throughout anterior pituitary . CONTROL OF HORMONE SECRETION IN ANTERIOR PITUITARY These axons store the regulatory hormones of the chromophils . These hormones are released by these axons into the primary capillary plexus and are conveyed to the 2ndry capillary plexus by the hypophyseal portal veins . Most of these releasing hormones are stimulatory , that stimulate the secretion by specific anterior pituitary cells . Two of the hypothalamic releasing hormones are inhibitory , that block hormone secretion in specific cells of anterior pituitary . CONTROL OF HORMONE SECRETION IN ANTERIOR PITUITARY • • Another mechanism controlling the activity of anterior pituitary cells is negative feed back by hormones from the target cells on the secretion of relevant hypothalamic factors and on hormone secretion by the specific anterior pituitary cells . Hormone secretion of anterior pituitary is also affected by other hormones e.g ghrelin secreted by stomach mucosa , also acts as releasing hormone for growth hormone secretion and oxytocin from posterior pituitary which increases prolactin during breast feeding . CLINICAL CORELATES • Benign pituitary adenomas often produce excessive numbers of functional acidophils and basophils . • Adenomas involving the somatotropic cells can cause gigantism in children or acromegaly in adults with musculoskeletal , neurologic and other medical consequences . NEUROHYPOPHYSIS Pituitary ) • Develops as a downward projection from the hypothalamus and consists of 3 divisions : • Median eminence • Infundibular stalk • Pars nervosa or the posterior lobe . • (unlike the anterior pituitary does not contain the cells that synthesize the 2 hormones ) • It is composed of neural tissue, containing some 100,000 secretory unmyelinated axons of large neurons with cell bodies in the supraoptic and paraventricluar nuclei of the hypothalamus . • Glial cells called pituicytes are also present , that resemble astrocytes , and are the most abundant cells in the posterior pituitary . (Posterior NEUROHYPOPHYSIS • The posterior lobe of the pituitary gland is not an endocrine gland . • It is a storage site for neurosecretions of the neurons of the supraoptic and paraventricular nuclei of the hypothalamus . (Posterior Pituitary ) NEUROHYPOPHYSIS (Posterior Pituitary) • The secretory neurons synthesize antidiuretic hormone (ADH) and oxytocin, which are then transported axonally into pars nervosa . • These hormones accumulate in axonal dilatations called neurosecretory bodies or Herring bodies which can be visible in the light microscope as lightly eosinophilic structures . • Herring bodies contain carrier protein called neurophysin . • Nerve impulses along the axons triggers the release of peptides from neurosecretory bodies , taken up by fenestrated capillaries of pars nervosa and the hormones are then released into general circulation . ULTRASTRUCTURE OF THE POSTERIOR PITUITARY • Electron microscopy reveals neurosecretory granules in unmyelinated axons and their terminal swellings (Herring bodies ) . • These small membrane bound secretory vesicles ( 120-200 nm in diameter) contain oxytocin or ADH combined with its specific neurophysins . • Axonal swellings have prominent mitochondria and many microtubules for axoplasmic transport . • Abundant sinusoidal capillaries with fenestrations are also seen .These capillaries are near axonal terminal filled with secretory vesicles , hence facilitating axonal discharge of hormone and rapid distribution of contents into the circulation . NEUROHYPOPHYSIS (Posterior Pituitary ) • ADH is released in response to increased blood tonicity , sensed by osmoreceptor cells in the hypothalamus . • ADH increases the permeability of renal collecting ducts to water , so that water reabsorption is increased, and osmotic balance of body fluids is restored . • ADH is also called arginine vasopressin • CLINICAL CORELATE : • Any head trauma affecting posterior pituitary , can lower the production of ADH , leading to a condition call Diabetes Insipidus , which is characterized by inability to concentrate urine , which lead to frequent urination (polyuria) and excessive thirst ( polydipsia ) NEUROHYPOPHYSIS (Posterior Pituitary ) • Oxytocin stimulates contraction of uterine smooth muscle during childbirth . • Oxytocin also acts on the myoepithelial cells in the mammary gland alveoli . • A nursing infant induces oxytocin secretion by stimulating sensory tracts that act on the hypothalamus (supraventricular nuclei) causing rapid ejection of milk . • Oxytocin also produces psychological effects such as promoting pair binding behavior. The Hypothalamic – Hypophyseal Tract & Blood Supply • The pituitary gland's neural connection to the brain and its blood supply are both of key importance for its function . • Embryologically , anatomically and functionally the pituitary gland is connected to hypothalamus , at the base of the brain . • The vascular portal system carries the small regulatory peptides from the hypothalamus to the adenohypophysis . • A bundle of axons called hypothalamic – hypophyseal tract courses into the neurohypophysis from two important hypothalamic nuclei . The Hypothalamic – Hypophyseal Tract & Blood Supply • Antidiuretic hormone (ADH) and oxytocin (both are peptides) are synthesized by the large neurons in the supraoptic and paraventricular nuclei, respectively . • Both hormones undergo axonal transport and accumulate temporarily in the axons of hypothalamic – hypophyseal tract before their release and uptake by large capillaries branching from inferior arteries . The Hypothalamic – Hypophyseal Tract & Blood Supply • The arteries supplying the pituitary gland are branches of internal carotid arteries and the veins are hypophyseal veins . • The superior hypophyseal arteries supply the median eminence and the infundibular stalk . • The inferior hypophyseal arteries supply the neurohypophysis . • HYPOTHALAMIC – HYPOPHYSEAL PORTAL SYSTEM : • The superior hypophyseal arteries give rise to a primary plexus of fenestrated capillaries that supply the stalk and the median eminence . • The hypophyseal portal veins drain the primary capillary plexus and deliver blood into the secondary plexus of fenestrated capillaries located in the pars distalis .