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Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
Posterior pituitary
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Posterior pituitary

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  1. Posterior pituitary د . بثينة عباس
  2. Posterior pituitary <ul><li>The posterior lobe of the pituitary releases two hormones, both synthesized in the hypothalamus, into the circulation. Vasopressin Vasopressin is a peptide of 9 amino acids (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly). It is also known as arginine vasopressin (AVP) and the antidiuretic hormone (ADH). Vasopressin acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood. This it acts to reduce the volume of urine formed (giving it its name of antidiuretic hormone). </li></ul>
  3. Posterior pituitary <ul><li>Vasopressin has a vital role in the control of tonicity of ECF and indirectly ICF and water balance. The neural impulse that trigger ADH are activated by increase osmolality of plasma is mediated by osmoreceptors located in the hypothalamus and by baroreceptor located in the heart and other regions in the vascular system. </li></ul>
  4. <ul><li>other stimuli include emotional and physical stress and pharmacological agent including acetyl choline, nicotine and morphine. Most these effects involve increased synthesis of ADH and neurophysin II. Excessive secretion results in dilutional Hyponatraemia with risk of water intoxication. Epinephrine and agents that expand plasma volume inhibit ADH Secretion as does ethanol. </li></ul>
  5. Thyroid hormone <ul><li>The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine -based hormones produced by the thyroid gland The thyroid gland, a butterfly-shaped structure in the lower part of the neck, normally produces a hormone called thyroxine. This hormone controls the rate of metabolism—all the physical and chemical processes that occur in cells to allow growth and maintain body functions. When the thyroid gland does not produce enough thyroxine, body processes slow down. An important component in the synthesis of thyroid hormones is iodine . The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half life than T3. The ratio of T4 to T3 released into the blood is roughly 20 to 1. Thyroxine is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase). </li></ul>
  6. Thyroid hormone <ul><li>Most of the thyroid hormone circulating in the blood is bound to transport proteins . Only a very small fraction of the circulating hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. </li></ul><ul><li>When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading. </li></ul>
  7. function <ul><li>The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate , affect protein synthesis , help regulate long bone growth (synergy with growth hormone ), neuronal maturation and increase the body's sensitivity to catecholamines (such as adrenaline ) by permissiveness . The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein , fat , and carbohydrate metabolism , affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. </li></ul>
  8. Synthesis <ul><li>Thyroid hormones are synthesised in adults as long as the dietary iodine is adequate supply to prevent goitre formation. The daily ingestion of iodide is 400-500g.The synthesis in the thyroid gland takes place in the following way: </li></ul><ul><li>A. Dietary iodine (I2) is reduced to iodide (I-) in the stomach and gut is rapidly absorbed and circulates as iodide. </li></ul><ul><li>B. Follicular cells in the thyroid gland possess an active iodide trap that requires and concentrates iodide from the circulating blood. Iodide is transported into the cell against an electrochemical gradient. </li></ul>
  9. <ul><li>The iodide pump is linked to a Na+-K+-pump, which requires energy in the form of oxidative phosphorylation (ATP). The thyroid absorption of iodide is also inhibited by negative ions (such as perchlorate, pertechnetate, thiocyanate and nitrate), because they compete with the iodide at the trap. In the follicular cell, iodide passes down its electrochemical gradient through the apical membrane and into the follicular colloid. Iodide is instantly oxidised – with hydrogen peroxide as oxidant - by a thyroid peroxidase to atomic or molecular iodine (I0 or I2) at the colloid surface of the apical membrane. Thiouracil and sulfonamides block this peroxidase. </li></ul>
  10. <ul><li>D. At the apical membrane the oxidised iodide is attached to the tyrosine units (L-tyrosine) in thyroglobulin at one or two positions, forming the hormone precursors mono-iodotyrosine (MIT), and di-iodotyrosine (DIT), respectively. This and the following reactions are dependent on thyroid peroxidase in the presence of hydrogen peroxide -both located at the apical membrane. As MIT couples to DIT it produces tri-iodothyronine (3,5,3`-T3), whereas two DIT molecules form tetra-iodothyronine (T4), or thyroxine. These two molecules are the two thyroid hormones. Small amounts of the inactive reverse T3 (3,3`,5`- T3) is also synthesised. </li></ul>
  11. <ul><li>C. The rough endoplasmic reticulum synthesises a large storage molecule called thyroglobulin. This compound is build up by a long peptide chain with tyrosine units and a carbohydrate unit completed by the Golgi apparatus. Iodide-free thyroglobulin is transported in vesicles to the apical membrane, where they fuse with the membrane and finally release thyroglobulin at the apical membrane. </li></ul>
  12. <ul><li>E. Each thyroglobulin molecule contains up to 4 residues of T4 and zero to one T3. Thyroglobulin is retrieved back into the follicular cell as colloid droplets by pinocytosis. Pseudopods engulf a pocket of colloid. These colloid droplets pass towards the basal membrane and fuse with lysosomes forming phagolysosomes. </li></ul><ul><li>F. Lysosomal exopeptidases break the binding between thyroglobulin and T4 (or T3). Large quantities of T4 are released to the capillary blood. Only minor quantities of T3 are secreted from the thyroid gland. </li></ul><ul><li>G. The proteolysis of thyroglobulin also releases MIT and DIT. These molecules are deiodinated by the enzyme deiodinase, whereby iodide can be reused into T4 or T3. Normally, only few intact thyroglobulin molecules leave the follicular cells. </li></ul><ul><li>H. TSH stimulates almost all processes involved in thyroid hormone synthesis and secretion. </li></ul>
  13.  
  14. Actions of thyroid hormones <ul><li>Thyroid hormones are lipid-soluble and pass through cell membranes easily. T3 binds to specific nuclear receptor proteins with an affinity that is tenfold greater than the affinity for T4. </li></ul><ul><li>Thyroid hormones stimulate oxygen consumption in almost all cells.Thyroid hormones stimulate the rate of 1) hepatic glucose output and peripheral glucose utilisation, 2) hepatic metabolism of fatty acids, cholesterol and triglycerides, 3) the synthesis of important proteins (the Na+-K+-pump, respiratory enzymes, erythropoietin, -adrenergic receptors, sex hormones, growth factors etc), 4) the absorption of carbohydrates in the intestine and the gut excretion of cholesterol, and 5) the modulation of reproductive function. </li></ul>
  15. Calcitonin <ul><li>Is produced by the parafollicular C-cells of the thyroid. Calcitonin inhibits bone resorption by blocking the parathyroid hormone (PTH)-receptors on the osteoclasts. The result is an extremely effective lowering of plasma-Ca2+  and -phosphate. Calcitonin is important in bone remodelling and in treatment of osteoporosis. </li></ul><ul><li>Calcitonin is a single-chain peptide with a disulphide ring, containing 32 amino acids. Calcitonin is secreted from the thyroid gland in response to hypercalcaemia and it acts to lower plasma [Ca2+], as opposed to the effect of PTH. </li></ul><ul><li>Administration of calcitonin leads to a rapid fall in plasma [Ca2+]. Calcitonin is the physiologic antagonist to PTH and inhibits Ca2+ -liberation from bone (ie, inhibits both osteolysis by osteocytes and bone resorption by osteoclasts). But calcitonin reduces plasma phosphate just as PTH. </li></ul>
  16. <ul><li>Calcitonin probably inhibits reabsorption of phospha¬te in the distal tubules of the kidney, but calcitonin also inhibits the renal reabsorp¬tion of Ca2+, Na+ and Mg2+. Calcitonin may inhibit gut absorption of Ca2+ and promote phosphate entrance into bone and cause important bone remodelling. </li></ul><ul><li>Calcitonin deficiency does not lead to hypercalcaemia, and excess calcitonin from tumours does not lead to hypocalcaemia. Therefore, most effects of calcitonin are evidently offset by appropriate regulation through the actions of PTH and vitamin D. </li></ul>
  17. <ul><li>Calcitonin in plasma declines with age and is lower in women than in men. Low levels of calcitonin are involved in accelerated bone loss with age and after menopause (osteoporosis). </li></ul><ul><li>Calcitonin protects the female skeleton from the drain of Ca2+ during pregnancy and lactation. </li></ul><ul><li>Calcitonin is a neurotransmitter in the hypothalamus and in other CNS locations. </li></ul><ul><li>Calcitonin is administered to postmenopausal females in attempt to prevent osteoporosis. </li></ul>
  18. Hyperthyroidism <ul><li>The classical hyperthyroidism or thyrotoxicosis (Graves thyroiditis) is a condition characterized by an abnormal rise in basal metabolic rate, struma and eye signs (thyroid eye disease). The eyes of the patient typically bulge (ie, exophtalmus). Patients with thyrotoxicosis have overwhelmingly high metabolic rates. </li></ul><ul><li>Thyroid eye disease (with exophtalmus) is not confined to Graves’s hyperthyroidism only. Some exophtalmus patients are euthyroid or hypothyroid. Common to all types of thyroid eye diseases are specific antibodies that cause inflammation of the retro-orbital tissue with swelling of the extraocular eye muscles, so they cannot move the eyes normally. Proptosis and lid lags are typical signs, and conjunctivitis and scars on the cornea follow due to lack of protective cover. </li></ul>
  19. Hyperthyroidism <ul><li>The oedematous retro-orbital tissue may force the eye balls forward and press on the optic nerve to such an extent that vision is impaired or blindness results. The best treatment is to normalise the accompanying thyrotoxicosis. TSH receptor antibody (IgG antibodies) release causes Graves’s disease from activated B-cells. A genetic deficiency is involved, which is shown by the 50% in monozygotic twins. Trigger mechanisms are presumed to be bacterial or viral infections producing autoimmune phenomena in genetically deficient individuals </li></ul>
  20. <ul><li>. The autoimmune system can produce the following autoantibodies: </li></ul><ul><li>TSH-receptor antibodies to the TSH receptors on the surface of the thyroid follicular cells, which they stimulate just like TSH itself, causing thyroid hypersecretion. These IgG antibodies are also termed long-acting thyroid stimulator. </li></ul><ul><li>Specific autoantibodies causing retro-orbital inflammation and thyroid eye disease. </li></ul><ul><li>Thyroglobin antibodies against the storage molecule, thyroglobin. </li></ul><ul><li>Microsomal antibodies against thyroid peroxidase. </li></ul>
  21. <ul><li>The increased metabolic rate and sympatho-adrenergic activity dominate the patient. The patient is anxious with warm and sweaty skin, tachycardia, palpitations, fine finger tremor, and pretibial myxoedema. Typically is a symmetrical, warm pulsating goitre. Lean hyperthyroid females - like female distance runners - have small fat stores and greatly reduced menstrual bleedings (oligomenorr¬hoea) or even amenorrhoea. The high T3 level increases the density of -adrenergic receptors on the myocardial cells. The cardiac output is high even at rest and arrhythmias are frequent (eg, atrial fibrillation). </li></ul><ul><li>Elderly patients may present with an apathetic hyperthyroidism, where they complain of tiredness. Measurement of serum TSH with T3/T4 reveals that the diagnosis is not hypo- but hyperthyroidism. Erroneous treatment with thyroid hormone can kill the patient by causing vasodilatation and cardiac output failure. </li></ul>
  22. <ul><li>A suppressed serum TSH confirms the diagnosis of hyperthyroidism, and the serum T3 or T4 is raised. </li></ul><ul><li>Several drugs are used in the treatment of hyperthyroidism. </li></ul><ul><li>Carbimazole and methimazole inhibit the production of thyroid hormone and have immuno-suppressive actions. </li></ul><ul><li>Monovalent anions and ouabain inhibit the iodide trap. </li></ul><ul><li>Thiocarbamide inhibits the iodination of tyrosyl residues. </li></ul><ul><li>Sulphonamides inhibit thyroid peroxidase, which oxidises iodide to iodine. </li></ul><ul><li>Large doses of iodide inhibit the TSH-receptors on the thyroid gland. </li></ul><ul><li>The high activity of the sympatho-adrenergic system is inhibited by -blockers, preferably with central sedative effects. </li></ul><ul><li>Subtotal thyroidectomy is used to treat patients with a large goitre, or patients with severe side effects to drug therapy. </li></ul><ul><li>Radioactive iodine is stored in the gland and destroys the follicle cells. This therapy is complicated, and some patients develop hypothyroidism. </li></ul>
  23. Hypothyroidism <ul><li>Primary hypothyroidism is an abnormally low activity of the thyroid gland with low circulating thyroid hormone levels caused by thyroid disease. Secondary hypothyroidism results from hypothalamic-pituitary disease. </li></ul><ul><li>Primary hypothyroidism is caused by microsomal autoantibodies precipitated in the glandular tissue. Lymphoid infiltration of the thyroid may eventually lead to atrophy with abnormally low production of T4. Another clinical form starts out as Hashimotos thyroiditis, often with hyperthyroidism and goitre. Following atrophy caused by microsomal autoantibodies, the condition ends as hypothyroidism, or the patient is euthyroid. </li></ul>
  24. <ul><li>When hypothyroidism is congenital both physical and mental development is impaired and cretinism is the result. Also iodide deficiency in childhood may also result in a cretin or a mentally retarded hypothyroid dwarf. </li></ul><ul><li>Myxoedema in the adult is severe thyroid gland hypothyroidism with a puffy swollen face due to a hard, non-pitting oedema (called myxoedema). The skin is dry and cold; there is bradycardia, often cardiomegaly (ie, myxoedema heart), hair loss, constipation, muscle weakness and anovulatory cycles in females. A high TSH level and a low total or free T4 in plasma confirms the diagnosis primary hypothyroidism. Thyroid autoantibodies are usually demonstrable in the plasma. Hypercholesterolaemia and increased concentrations of liver and muscle enzymes (aspartate transferase, creatine kinase) in the plasma is typical. </li></ul>
  25. <ul><li>As stated thyroid gland high TSH characterises hypothyroidism. A test dose of TSH to a patient with thyroid hypothyroidism will not stimulate the thyroid gland. </li></ul><ul><li>A test dose of TRH will result in an increased TSH response in thyroid gland hypothyroidism and decrease in hyperthyroidism. This is due to the negative feedback of thyroid hormones on the hypophysis. Hypothyroid females often have ex¬cessive and frequent menstrual bleedings (menorrhagia and polymenorrhoea). Hypothyroid patients exhibit slow cardiac activity. </li></ul><ul><li>Secondary hypothyroidism is caused by reduced TSH drive due to pituitary or hypothalamic insufficiency. A test dose of TRH to a myxoedema patient with hypothalamic or pituitary insufficiency will result in a normal TSH response. </li></ul><ul><li>Replacement is given to the hypothyroid patient with approximately 100 g T4 daily for the rest of the patients life. </li></ul>
  26. The Parathyroid Glands <ul><li>The parathyroid glands are 4 tiny structures embedded in the rear surface of the thyroid gland. They secrete parathyroid hormone ( PTH ) a polypeptide of 84 amino acids. PTH increases the concentration of Ca2+ in the blood in three ways. PTH promotes release of Ca2+ from the huge reservoir in the bones. (99% of the calcium in the body is incorporated in our bones.) </li></ul><ul><li>reabsorption of Ca2+ from the fluid in the tubules in the kidneys </li></ul><ul><li>absorption of Ca2+ from the contents of the intestine (this action is mediated by calcitriol , the active form of vitamin D .) </li></ul><ul><li>PTH also regulates the level of phosphate in the blood. Secretion of PTH reduces the efficiency with which phosphate is reclaimed in the proximal tubules of the kidney causing a drop in the phosphate concentration of the blood. </li></ul>
  27. Control of the Parathyroids: the calcium receptor <ul><li>The cells of the parathyroid glands have surface G-protein-coupled receptors that bind Ca2+ (the same type of receptor is found on the calcitonin-secreting cells of the thyroid and on the calcium absorbing cells of the kidneys). Binding of Ca2+ to this receptor depresses the secretion of PTH and thus leads to a lowering of the concentration of Ca2+ in the blood. Two classes of inherited disorders involving mutant genes encoding the Ca2+ receptor occur: </li></ul><ul><li>loss-of-function mutations with the mutant receptor always &quot;off&quot;. Patients with this disorder have high levels of Ca2+ in their blood and excrete small amounts of Ca2+ in their urine. This causes hyper parathyroidism . </li></ul><ul><li>gain-of-function mutations with the mutant receptor always &quot;on&quot; (as though it had bound Ca2+). People with this disorder have low levels of Ca2+ in their blood and excrete large amounts of Ca2+ in their urine. This causes hypo parathyroidism </li></ul>
  28. <ul><li>Rare autoimmune disorders can mimic one or the other of these inherited disorders. In each case, autoantibodies bind to the receptors. </li></ul><ul><li>If these inhibit the receptors, they cause hyper parathyroidism. </li></ul><ul><li>If they activate the receptors (like those in Graves' disease ), they cause hypo parathyroidism </li></ul>
  29. Hyperparathyroidism <ul><li>Tumors in the parathyroids elevate the level of PTH causing a rise in the level of blood Ca2+ at the expense of calcium stores in the bones. So much calcium may be withdrawn from the bones that they become brittle and break. </li></ul><ul><li>Until recently, treatment has been the removal of most — but not all — of the parathyroid tissue (i.e. the goal is the removal of 3 1/2 glands). Now clinical trials have begun on a drug (designated R-568) that mimics the action of calcium on the parathyroids, resulting in a drop in PTH and blood Ca2+ and sparing the calcium stores in the bone </li></ul>
  30. Hypoparathyroidism <ul><li>Causes: </li></ul><ul><li>accidental removal of or damage to the parathyroids during neck surgery </li></ul><ul><li>inherited mutations in the PTH gene </li></ul><ul><li>inherited predisposition to an autoimmune attack against the parathyroids (and other glands) </li></ul><ul><li>inherited defect in the embryonic development of the parathyroids (DiGeorge syndrome) </li></ul><ul><li>Treatment: </li></ul><ul><li>give calcium supplements </li></ul><ul><li>give calcitriol (1,25[OH]2 vitamin D3) </li></ul><ul><li>give teriparatide (Forteo®), a synthetic (by recombinant DNA ) version of PTH (containing only the 34 amino acids at the N-terminal ). </li></ul>

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