![Vitamin D Synthesis
• PTH increases the activity of 1-α-hydroxylase enzyme, which converts 25-
hydroxycholecalciferol to 1, 25-dihydroxycholecalciferol, the active form of vitamin
D.
Regulation of PTH Secretion
• Secretion of parathyroid hormone is chiefly controlled by serum [Ca2+] through
negative feedback, which is achieved by the activation of calcium-sensing receptors
located on parathyroid cells.](https://image.slidesharecdn.com/13-241112182811-bf87bcb9/85/13-ENDOCRINE-SYSTEM-FOR-BEST-LEARNING-AND-EXPANDING-KNOWLEDGE-95-320.jpg)
![• Stimulators
• Decreased serum [Ca2+].
• Mild decreases in serum [Mg2+].
• An increase in serum phosphate (Since increased phosphate will complex
with serum calcium to form calcium phosphate, this causes the Ca sensitive
receptors (CaSr) to think that serum Ca has decreased, as CaSR do not sense
Calcium phosphate, thereby triggering an increase in PTH).
Inhibitors
• Increased serum [Ca2+].
• Severe decreases in serum [Mg2+], which also produces symptoms of
hypoparathyroidism (such as hypocalcemia).](https://image.slidesharecdn.com/13-241112182811-bf87bcb9/85/13-ENDOCRINE-SYSTEM-FOR-BEST-LEARNING-AND-EXPANDING-KNOWLEDGE-96-320.jpg)
13. ENDOCRINE SYSTEM FOR BEST LEARNING AND EXPANDING KNOWLEDGE
- 1. DESCRIBE STRUCTURAL ORGANIZATION OF ENDOCRINE SYSTEM BY DR HERIEL (MD)
- 2. Introduction to Endocrine System and Hypothalamus • The endocrine system consists of glands widely separated from each other with no direct links. • Endocrine glands consist of groups of secretory cells surrounded by an extensive network of capillaries that facilitates diffusion of hormones (chemical messengers) from the secretory cells into the bloodstream. • Hormone is a chemical substance produced in the body which has a specific regulatory effect on the activity of certain cells or a certain organ. • Endocrine glands are commonly referred to as the ductless glands because the hormones diffuse directly into the bloodstream. • The hormone is then carried in the bloodstream to target tissues and organs that may be quite distant, where they influence cellular growth and metabolism.
- 3. • The major endocrine glands in the body are, o Hypothalamus o Pituitary gland o Thyroid gland o Parathyroid gland o Adrenal gland o Pancreatic Islet o Ovaries o Testes in males
- 4. Major Endocrine Gland in The Body
- 5. Classification of Hormones Classification of Hormones Based on General Function Hormones • Tropic hormones, hormones that target other endocrine glands and stimulate their growth and secretion, tropic hormones are hormones produced and secreted by the anterior pituitary which target endocrine glands. Tropic hormones include o Thyroid-stimulating hormone (TSH or thyrotrophic) - stimulates the thyroid gland to make and release thyroid hormone. o Adrenocorticotropic hormone (ACTH or corticotrophin) - stimulates the adrenal cortex to release glucocorticoids. o Luteinizing hormone (LH) - stimulates the release of steroid hormones in gonads— the ovary and testes. o Follicle-stimulating hormone (FSH) - stimulates the maturation of eggs and production of sperm. • The hypothalamus controls the release of tropic hormones by secreting a class of hypothalamic neuro-hormones called releasing and release-inhibiting hormones, which are released to the hypothalamo-hypophyseal portal system and act on the anterior pituitary.
- 6. • Anabolic hormones (hormones that stimulate anabolism in their target cells), Anabolism is the set of metabolic pathways that construct molecules from smaller units. o These reactions require energy. o One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite. o Anabolism is powered by catabolism, where large molecules are broken down into smaller parts and then used up in respiration. o Many anabolic processes are powered by adenosine triphosphate (ATP). o Anabolic processes tend toward building up organs and tissues. o These processes produce growth and differentiation of cells and increase in body size a process that involves synthesis of complex molecules. o Examples of anabolic processes include the growth and mineralization of bone and increases in muscle mass. o Endocrinologists have traditionally classified hormones as anabolic or catabolic, depending on which part of metabolism they stimulate. o The classic anabolic hormones are the anabolic steroids, which stimulate protein synthesis and muscle growth.
- 7. o The balance between anabolism and catabolism is also regulated by circadian rhythms, with processes such as glucose metabolism fluctuating to match an animal's normal periods of activity throughout the day. o Classic anabolic hormones Growth hormone GF1 and other insulin-like growth factors Insulin Testosterone Estradiol • Sex hormones, hormones that target reproductive tissue. o Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. o Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades.
- 8. o The term sex hormone is nearly always synonymous with sex steroid. o Production, natural sex steroids are made by the (ovaries or testes), by adrenal glands, or by conversion from other sex steroids in other tissue such as liver or fat. o Synthetic sex steroids, there are also many synthetic sex steroids. o Synthetic androgens are often referred to as anabolic steroids. o Synthetic estrogens and progestins are used in methods of hormonal contraception. o Ethinylestradiol is a semi-synthetic estrogen.
- 9. o Specific compounds that have partial agonist activity for steroid receptors, and therefore act in part like natural steroid hormones, are in use in medical conditions that require treatment with steroid in one cell type, but where systemic effects of the particular steroid in the entire organism are only desirable within certain limits. o Types, in many contexts, the two main classes of sex steroids are androgens and estrogens, of which the most important human derivatives are testosterone and estradiol, respectively. o Other contexts will include progestagen as a third class of sex steroids, distinct from androgens and estrogens. o Progesterone is the most important and only naturally occurring human progestagen. • o In general, androgens are considered male sex hormones, since they have masculinizing effects, while estrogens and progestagens are considered female sex hormones although all types are present in each gender, albeit at different levels. • o Sex steroids include Androgens,testosterone,androstenedione,dehydroepiandrosterone,anabolic steroids Estrogens, estradiol, estrone ,estriol Progestagens, progesterone, progestins striker
- 10. Division of Hormones Based on Chemical Structure • Steroids hormones, these are manufactured by endocrine cells from cholesterol. They are lipid soluble and can easily pass through the phospholipids plasma membrane of target cells. • Non steroid hormones o Are synthesized primarily from amino acids. Some of non-steroids hormones are protein hormones like growth hormones prolactin, parathyroid hormone, calcitonin, adrenocorticotropic hormone (ACTH) insulin and glucagon. o Protein hormones that have carbohydrates groups attached to their amino acid chains are often classified as glycoprotein hormones these include follicle-stimulating hormones (FSH), luteinizing hormone (LH), and chorionic gonadotropin (CG). o Another group of nonsteroid hormones are antidiuretic hormones (ADH), oxytocin, melanocyte-stimulating hormone (MSH), somatostatin, thyrotropin-releasing hormone (TRH) and gonadotropin realising hormone. o Another category of nonsteroid hormones consists of the amino acid derivative hormones. They are derived from a single molecule of amino acid they are divided into amine hormones such as noradrenalin, adrenalin and melatonin. o The other group is synthesized by adding iodine atom these are thyroxine T4 and Triiodothyronine T3
- 11. Endocrine Glands and its Hormones
- 12. Importance and Functions of Endocrine System • The autonomic nervous system is concerned with rapid changes, while hormones of the endocrine system are mainly involved in slower and more precise adjustments. • Hormones have the following effects on the body o Stimulation or inhibition of growth o Mood swings o Induction or suppression of apoptosis (programmed cell death) o Activation or inhibition of the immune system o Regulation of metabolism o Preparation of the body for mating, fighting, fleeing, and other activity o Preparation of the body for a new phase of life, such as puberty, parenting, and menopause o Control of the reproductive cycle o Hunger cravings • A hormone may also regulate the production and release of other hormones. Hormone signals control the internal environment of the body through homeostasis. • The endocrine system consists of a number of distinct glands and some tissues in other organs.
- 13. • Energy balance, metabolism, & nutrition o The endocrine system, like the nervous system, adjusts and correlates the activities of the various body systems, making them appropriate to the changing demands of the external and internal environment. o Endocrine integration is brought about by chemical signals secreted by ductless glands and transported in the circulation to target cells. o The hormones regulate metabolic processes. o The term metabolism, literally meaning change, is used to refer to all the chemical and energy transformations that occur in the body. o The animal organism oxidizes carbohydrates, proteins, and fats, producing principally CO2, H2O, and the energy necessary for life processes. CO2, H2O, and energy are also produced when food is burned outside the body. o In the body, oxidation is not a one-step, semiexplosive reaction but a complex, slow, stepwise process called catabolism, which liberates energy in small, usable amounts. Energy can be stored in the body in the form of special energy-rich phosphate compounds and in the form of proteins, fats, and complex carbohydrates synthesized from simpler molecules. o Formation of these substances by processes that take up rather than liberate energy is called anabolism.
- 14. • The hypothalamus is classified as a part of the brain and not as an endocrine gland it controls the pituitary gland and has an indirect effect on many others. • When a hormone arrives at its target cell, it binds to a specific area called the receptor, where it acts as a switch influencing chemical or metabolic reactions inside the cell. • The receptors for peptide hormones are situated on cell membrane and those for lipid based hormone inside the cell. • Examples of lipid based hormones are glucocorticoids, mineralocorticoids and thyroid hormones. • Examples of peptide hormones are adrenaline and nor-adrenaline, insulin and glucagon.
- 15. Regulation and Control of Hormones in the Body • In biology regulation means to control something. • Regulating hormones means controlling how much hormones are made and released from cells. Negative Feedback • Hormone regulation is mostly done by negative feedback. • In negative feedback a hormone makes an effect. • The cells that make the hormone see that effect happen. • When they see it happen, they stop making more hormones. • A good example of negative feedback is the hormone insulin. Insulin is a hormone that is made by the pancreas. • Insulin is released by the pancreas when you eat glucose (a kind of sugar). The glucose, goes from your stomach to the blood. • The amount of glucose in the blood goes up. The pancreas sees this high glucose level. It makes insulin and releases it into the blood. • Then the insulin goes through the whole body and tells cells to take glucose out of the blood. • Cells use some of this for energy. But some extra is also saved in the cells to use later.
- 17. • When cells take up glucose from the blood this makes the glucose level go down. • The pancreas sees this and stops making insulin. When the pancreas stops sending this message (insulin), the cells in the body stop taking extra glucose out of the blood. • So the negative feedback works to keep the blood glucose level normal. If glucose is high, the pancreas makes insulin. • The insulin causes the glucose to fall. Then this lower level of glucose tells the pancreas to stop making insulin.
- 18. Counter Regulatory Hormones • Sometimes two or more hormones control the same thing. For example, blood glucose is very important to an organism. • So it is not controlled by just one hormone. Other hormones also make the glucose level go up or down. • If the glucose level gets too low, the body releases hormones that do the opposite of insulin. They do not tell the cells in the body to take up glucose from the blood. They tell the cells to put glucose back into the blood. • These kinds of hormones that work opposite of other hormones are called counter-regulatory hormones. • Counter-regulatory hormones for insulin are glucagon and epinephrine.
- 19. Positive Feedback • Most important things in an organism are kept in homeostasis by negative feedback and counter- regulatory hormones. • Few things are controlled in different ways. • One rare way is positive feedback. In negative feedback, the hormone's effect makes a gland stop making hormones. In positive feedback the opposite happens. The effect of the hormone tells the gland to make even more hormones. • An example of positive feedback is the hormone that causes childbirth (when babies are born). • The hormone that causes this is oxytocin. This hormone is made by the pituitary gland. • When the baby starts coming out, it stretches the muscle in the cervix (the bottom of the womb.) • Nerves in the cervix send a message to the pituitary. This message makes the pituitary release more oxytocin. • The oxytocin then causes the muscles of the womb to contract, or squeeze. This causes more stretching in the cervix. • This stretching then tells the pituitary to make even more oxytocin. So levels of oxytocin keep rising until the squeezing or contractions of the womb force the baby out.
- 21. • The level of a hormone in the blood is variable and self-regulating within its normal range. • A hormone is released in response to a specific stimulus and usually its action reverses or negates the stimulus through a negative feedback mechanism. • The effect of a positive feedback mechanism is amplification of the stimulus and increasing release of the hormone until a particular process is complete and the stimulus ceases, e.g. release of oxytocin during labour.
- 22. Structure and Functions of Hypothalamus Location of Human Hypothalamus
- 23. Medial View of Brain Showing the Position of Hypothalamus
- 24. • The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. • One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland (hypophysis). • The hypothalamus is located below the thalamus, just above the brain stem. • In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is roughly the size of an almond. • The hypothalamus is responsible for certain metabolic processes and other activities of the autonomic nervous system. • It synthesizes and secretes neurohormones, often called hypothalamic-releasing hormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. • The hypothalamus controls body temperature, hunger, thirst, fatigue, and circadian cycles.
- 25. • The hypothalamus is a complex region in the brain of humans, and even small nuclei within the hypothalamus are involved in many different functions. • The paraventricular nucleus for instance contains oxytocin and vasopressin (also called antidiuretic hormone) neurons which project to the posterior pituitary, but also contains neurons that regulate ACTH and TSH secretion (which project to the anterior pituitary), gastric reflexes, maternal behavior, blood pressure, feeding, immune responses, and temperature. • The hypothalamus co-ordinates many hormonal and behavioural circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and many important behaviours. • The hypothalamus must therefore respond to many different signals, some of which are generated externally and some internally. o It is thus richly connected with many parts of the central nervous system, including the brainstem reticular formation and autonomic zones, the limbic forebrain(particularly the amygdala, septum, diagonal band of Broca, and the olfactory bulbs, and the cerebral cortex).
- 26. • The hypothalamus is responsive to o Light-day length and photoperiod for regulating circadian and seasonal rhythms. o Olfactory stimuli, including pheromones o Steroids, including gonadal steroids and corticosteroids o Neurally transmitted information arising in particular from the heart, the stomach, and the reproductive tract o Autonomic inputs o Blood-borne stimuli, including leptin, ghrelin, angiotensin, insulin, pituitary hormones, cytokines, plasma concentrations of glucose and osmolarity o Stress o Invading microorganisms by increasing body temperature, resetting the body's thermostat upward
- 27. Neural Inputs • The hypothalamus receives many inputs from the brainstem, notably from the nucleus of the solitary tract, the locus coeruleus, and the ventrolateral medulla. • Oxytocin secretion in response to suckling or vagino-cervical stimulation is mediated by some of these pathways, vasopressin secretion in response to cardiovascular stimuli arising from chemoreceptors in the carotid sinus and aortic arch, and from low-pressure atrial volume receptors, is mediated by others. • These effects are all mediated by the hypothalamus, and the information is carried mainly by spinal pathways that relay in the brainstem. • Stimulation of the nipples stimulates release of oxytocin and prolactin and suppresses the release of LH and FSH. • Cardiovascular stimuli are carried by the vagus nerve, but the vagus also conveys a variety of visceral information, including for instance signals arising from gastric distension to suppress feeding. Again this information reaches the hypothalamus via relays in the brainstem.
- 28. Blood-Borne Stimuli • Peptide hormones have important influences upon the hypothalamus, and to do so they must evade the blood-brain barrier. • The hypothalamus is bounded in part by specialized brain regions that lack an effective blood-brain barrier. The capillary endothelium at these sites is fenestrated to allow free passage of even large proteins and other molecules. • Some of these sites are the sites of neurosecretion, the neurohypophysis and the median eminence. • These structures are densely vascularized, and contain osmoreceptive and sodium receptive neurons which control drinking, vasopressin release, sodium excretion, and sodium appetite. • They also contain neurons with receptors for angiotensin, atrial natriuretic factor, endothelin and relaxin, each of which is important in the regulation of fluid and electrolyte balance.
- 29. • It is not clear how all peptides that influence hypothalamic activity gain the necessary access. In the case of prolactin and leptin, there is evidence of active uptake at the choroid plexus from blood into CSF. • Some pituitary hormones have a negative feedback influence upon hypothalamic secretion, for example, growth hormone feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of prolactin and TSH. • The hypothalamus functions as a type of thermostat for the body. It sets a desired body temperature, and stimulates either heat production or retention to raise the blood temperature to a higher setting, or sweating and vasodilation to cool the blood to a lower temperature. • All fevers result from a raised setting in the hypothalamus, elevated body temperatures due to any other cause are classified as hyperthermia. o Rarely, direct damage to the hypothalamus, such as from a stroke, will cause a fever; this is sometimes called a hypothalamic fever. o It is more common for such damage to cause abnormally low body temperatures.
- 30. Steroids • The hypothalamus contains neurons that react strongly to steroids and glucocorticoids (the steroid hormones of the adrenal gland, released in response to ACTH). o It also contains specialised glucose-sensitive neurons (in the arcuate nucleus and ventromedial hypothalamus), which are important for appetite. • The preoptic area contains thermosensitive neurons; these are important for TRH secretion.
- 32. Hormones of the Pituitary Gland Structure of the Pituitary Gland (15 minutes) • The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g. • It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica) covered by a dural fold (diaphragma sellae). • The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in • the middle cranial fossa at the base of the brain. • • It is considered a master gland. • • The pituitary gland secretes hormones regulating homeostasis, including tropic hormones • that stimulate other endocrine glands. • • It is functionally connected to the hypothalamus by the median eminence. • • Located at the base of the brain, the pituitary is composed of two lobes: the anterior • pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis).
- 33. • The pituitary is functionally linked to the hypothalamus by the pituitary stalk, whereby hypothalamic releasing factors are released and, in turn, stimulate the release of pituitary hormones. • Although the pituitary gland is known as the master endocrine gland, both of its lobes are under the control of the hypothalamus. • The pituitary gland itself consists of three sections: o The anterior lobe o The intermediate lobe o The posterior lobe
- 34. • Histologically the gland composed of three types of stains; these are o Chromophobes (afraid of colour) o Acidophils (acid stain lover) o Basophils (base stain lover) • Functionally the cells are divided into o Somatotrophs – secrete growth hormone o Corticotrophs – secrete adrenocorticotropic hormone (ACTH) and melanocyte – stimulating hormone (MSH) o Thyrotrophs – secrete thyroid stimulating (TSH) Lactotrophs – secretes luteinizing hormone(LH) and follicle stimulating hormone(FSH)
- 35. GROWTH HORMONE(SOMATOTROPIN HORMONE) • This is the most abundant hormone synthesized by anterior pituitary gland. • It stimulates growth and division of most body cells especially that of bones and skeletal muscles. • It also regulates metabolism in many organs example, stimulates protein synthesis and break down of fats. • Stimulate growth by stimulating the liver to produce certain growth factors, which in turn accelerate amino acid transport into cells. • Rapid entrance of amino acids from the blood into the cells allows protein anabolism within the cell to accelerate.
- 37. • Increased protein anabolism allows increased rate of growth. o Growth promotes the growth of bone, muscle and other tissues. o Stimulates fat metabolism. o Accelerates mobilization of lipid from storage in adipose cells and speeds up the catabolism of those lipids after they have entered other cells. o Indirectly inhibit glucose metabolism and increases blood glucose levels. o This growth hormone is said to have a hyperglycemic effect. • Hypersecretion of Growth during the growth years before ossification of the epiphyseal plates causes an abnormally rapid rate of skeletal growth. • This condition is known as gigantism. • Hypersecretion after skeletal fusion has occurred can result in acromegally (abnormal enlargement of hands, feet, face and jaw causing separation of the teeth. • Hyposecretion of growth hormone during growth years may result in stunted body growth, known as pituitary dwarfism.
- 38. Prolactin and other Tropic Hormones • Produced by acidophils cells is also called lactogenic hormone. o It initiates milk secretion (lactation). o During pregnancy, a high level of prolactin promotes the development of the breast in anticipation of milk secretion. o Hypersecretion of PRL may cause lactation in non nursing women, disruption of the menstrual cycle and importence in men. o Hyposecretion of PRL is usually insignificant except in women who want to nurse their children. Tropic Hormones • Tropic hormones are hormones that have a stimulating effect on other endocrine glands. • These hormones stimulate the development of their target glands and tend to stimulate synthesis and secretion of the target hormone.
- 39. • Four principal tropic hormones are produced and secreted by the basophils cells. o Thyroid- Stimulating Hormone or thyrotropin. Promotes and maintains the growth and development of its target gland – the thyroid. TSH also causes the thyroid gland to secrete its hormones. It stimulates growth and activity of the thyroid gland, which secretes the hormones thyroxine (T4) and triiiodothyronine (T3). Release is lowest in the early evening and highest during the night. Secretion is regulated by a negative feedback mechanism. When the blood level of thyroid hormones is high, secretion of TSH is reduced, and vice versa.
- 40. o Adrenocorticosteroid (ACTH) or adrenalcorticotropin. Corticotrophin releasing hormone (CRH) from the hypothalamus promotes the synthesis and release of ACTH by the anterior pituitary. This increases the concentration of cholesterol and steroids within the adrenal cortex and the output of steroid hormones, especially cortisol. ACTH levels are highest at about 8 a.m. and fall to their lowest about midnight, although high levels sometimes occur at midday and 6 p.m. This circadian rhythm is maintained throughout life. It is associated with the sleep pattern and adjustment to changes takes several days, following, e.g., changing work shifts, travelling to a different time zone (Jet lag). Promotes and maintains normal growth and development of the cortex of the adrenal gland. Stimulates the adrenal cortex to synthesize and secrete some of its hormones
- 41. o Gonadotrophin: There are two gonadotrophins which are released by anterior Pituitary gland. o These are Follicle stimulating hormone and Lutenizing hormone. o Follicle-Stimulating hormone (FSH) Stimulates structure within the ovaries, primary follicle, to grow toward maturity. Each follicle contains a developing egg cell (ovum), which is released from the ovary during ovulation. FSH stimulate the follicle to synthesize and secrete estrogen (female sex hormones Oestrogen and Progesterone) in the male, FSH stimulates the development of the seminiferous tubules of the testes and maintains spermatogenesis (sperm production) by them.
- 42. Luteinizing Hormone (LH) • Stimulates the formation and activity of the corpus luteum of the ovary. • The corpus luteum (meaning yellow body) is the tissue left behind when a follicle ruptures to release its egg during ovulation. • The corpus luteum secretes progesterone and estrogeus when stimulated by LH. • LH supports FSH in stimulating the maturation of follicles. • In males, LH stimulates interstitial cells in the testes to develop, the synthesize and secrete testosterone (the male sex hormone testosterone). • FSH and LH are called gonodotropins because they stimulate the growth and maintenance of the gonads (ovaries and testes).
- 43. Intermediate Lobe • There is also an intermediate lobe in many animals. • In adult humans, it is just a thin layer of cells between the anterior and posterior pituitary. • The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary. • Melanocyte-Stimulating Hormone is secreted by basophil cells. • Stimulate melanocytes in the skin to produce more melanin and thus darken the skin. • MSH, ACTH and other skin-darkening hormones (such as estrogen and progesterone) work together to modulate the pigmentation of normal skin.
- 44. Control of Secretion in the Adenohypophysis • Hypothalamus secretes releasing hormones into the blood and travel through a complex of small blood vessels called hypophyseal portal system. • A portal system is an arrangement of blood vessels in which blood existing one tissue is immediately carried to a second tissue before being returned to the heart and lungs for oxygenation and redistribution and redistribution. • The hypophyseal portal system carries blood from the hypothalamus directly to the adenohypophysis where the target cells of the releasing hormones are located. • The releasing hormones that arrive in the adenohypophysis by means of this portal system influence the secretion of hormones by acidophils and basophils.
- 45. • The following is a list of some of the important hormones secreted by the hypothalamus into the hypophyseal portal system. o Growth hormone – releasing hormone o Growth hormone – inhibiting hormone (somatostatin) o Thyrotropin – releasing hormone o Corticotrophin – releasing hormone o Gonadotropin – releasing hormone o Prolactin – releasing hormone o Prolactin inhibiting hormone • Through negative feedback mechanisms, the hypothalamus adjusts the secretions of the addenohypophysis adjusts the secretions of its target glands, which in turn adjust the activity of their target tissues.
- 46. Feedback Mechanism • • That is, when there is a low level of a hormone in the blood supplying the hypothalamus it produces the appropriate releasing hormone that stimulates release of a trophic hormone by the anterior pituitary. • This in turn stimulates the target gland to produce and release its hormone. • As a result the blood level of that hormone rises and inhibits the secretion of releasing factor by the hypothalamus.
- 47. Posterior Pituitary (Neurohypophysis) • This is formed from nervous tissue and consists of nerve cells surrounded by supporting cells called pituicytes. • The gland secretes Antidiuretic hormone and Oxytocin. • These are synthesized hormones are synthesized in the hypothalamus and the stored in the axonal terminals within the posterior Pituitary gland. • So the posterior pituitary stores and releases. • Posterior pituitary hormones are synthesised in the nerve cell bodies, transported along the axons and then stored in vesicles within the axon terminals within the posterior pituitary their release by exocytosis is trigggered by nerve impulses from the hypothalamus.
- 48. • Oxytocin is one of the few hormones to create a positive feedback loop most of which is released from the paraventricular nucleus in the hypothalamus. o For example, uterine contractions stimulate the release of oxytocin from the posterior pituitary, which, in turn, increases uterine contractions. o This positive feedback loop continues throughout labor. o This stimulates two target tissues during and after child birth. o These tissues are uterine smooth muscles and muscle cells of lactating breast. o Inhibition occurs after delivery when uterine contractions no longer dilate (stretch) the cervix. o Oxytocin also stimulates contractions of the milk ducts in the breast, which move milk to the nipple (the let-down) in lactating women.
- 49. • Antidiuretic hormone (ADH, also known as vasopressin and AVP, arginine vasopressin), the majority of which is released from the supraoptic nucleus in the hypothalamus. • The main effect of ADH is to regulate fluid balance in the body by reducing the urine output, for instance during thirsty, hypotension and when there is high plasma osmolarity and during stress. • At high concentrations, for example after severe blood, ADH causes smooth muscle contraction, especially vasoconstriction in the blood vessels of the skin and abdominal organs. • This has a pressor effect, raising systemic blood pressure; the alternative name of this hormone, vasopressin, reflects this effect.
- 53. Adrenal Glands, Pancreas and Local Hormones • Structure and blood supply of the adrenal gland. • Anatomically, the adrenal glands(suprarenal) are located in the thoracic abdomen situated on top of the kidneys, one on each side, specifically on their anterosuperior aspect. • They are also surrounded by the adipose capsule and renal fascia. • In humans, the adrenal glands are found at the level of the 12th thoracic vertebra and receive their blood supply from the adrenal arteries. • The adrenal gland is separated into two distinct structures, both of which receive regulatory input from the nervous system. • They consists of two parts, the outer cortex and the inner medulla. • It secretes hormones that influence the body`s metabolism, blood chemicals, and body characteristics, as well as influence the part of the nervous system that is involved in the response and defense against stress.
- 54. Adrenal cortex. • The adrenal cortex is devoted to the synthesis of corticosteroid hormones from cholesterol. Some cells belong to the hypothalamic- pituitary-adrenal axis and are the source of cortisol and corticosterone synthesis. • Under normal unstressed conditions, the human adrenal glands produce the equivalent of 35-40mg of cortisone acetate per day.
- 55. • Other cortical cells produce androgens such as testosterone, while some regulate water and electrolyte concentrations by secreting aldosterone. • In contrast to the direct innervation of the medulla, the cortex is regulated by neuroendocrine hormones secreted by the pituitary gland and hypothalamus, as well as by the renin-angiotensin system. • The cortex is divided into three zones, or layers. • This division is sometimes referred to as ‘functional zonation’.
- 56. • Moving from the outermost layer in: o Zona glomerulosa, the zona glomerulosa is the main site for production of mineralocorticoids, namely aldosterone, which plays an important role in the body's sodium homeostasis. o Zona fasciculata, the zona fasciculata is responsible for producing glucocorticoids, chiefly cortisol in humans. o Cortisol secretion is stimulated by adrenocorticotropic hormone (ACTH) from the anterior pituitary, by binding to a cell surface receptor and in turn increasing intracellular cAMP. o In the absence of ACTH, the zona fasciculata secretes a basal level of cortisol. o Zona reticularis, the zona reticularis produces androgens, mainly dehydroepiandrosterone (DHEA) and DHEA sulfate in humans.
- 57. Adrenal Medulla • The adrenal medulla is the core of the adrenal gland, and is surrounded by the adrenal cortex. • The chromaffin cells of the medulla are the body's main source of the circulating catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). • These water-soluble hormones, derived from the amino acid tyrosine, are part of the fight-or-flight response initiated by the sympathetic nervous system. • The adrenal medulla can be considered as specialized ganglion of the sympathetic nervous system, lacking distinct synapses, instead releasing secretions directly into the blood. • Noradrenaline is the postganglionic neurotransmitter of the sympathetic division of the autonomic nervous system. • Adrenaline and some noradrenaline are released into the blood from the adrenal medulla during stimulation of the sympathetic nervous system they are structurally very similar and this explains their similar effects.
- 58. • Together they potentiate the fight or flight response by: o Increasing heart rate. o Increasing blood pressure. o Diverting blood to essential organs including the heart, brain and skeletal muscles by dilating their blood vessels and constricting those of less essential organs, such as the skin. o Increasing metabolic rate. o Dilating the pupils. • Adrenaline has a greater effect on the heart and metabolic processes whereas noradrenaline has more influence on blood vessels.
- 60. Blood supply to Adrenal Gland. • Although variations of the blood supply to the adrenal glands (and indeed the kidneys themselves) are common, there are usually three arteries that supply each adrenal gland: o The superior suprarenal artery is provided by the inferior phrenic artery. o The middle suprarenal artery is provided by the abdominal aorta. o The inferior suprarenal artery is provided by the renal artery. • Venous drainage of the adrenal glands is achieved via the suprarenal veins: o The right suprarenal vein drains into the inferior vena cava. o The left suprarenal vein drains into the left renal vein or the left inferior phrenic vein. • The suprarenal veins may form anastomoses with the inferior phrenic veins. • The adrenal glands and the thyroid gland are the organs that have the greatest blood supply per gram of tissue. Up to 60 arterioles may enter each adrenal gland.
- 61. Hormones of the Adrenal Cortex • The adrenal cortex produces three groups of steroid hormones from cholesterol. • They are collectively called adrenocorticocoids (corticosteroids, corticoids). • They are: o Glucocorticoids o Mineralocorticoids o Sex hormones (androgens) • The hormones in each group have different characteristic actions but due to their structural similarity the actions may overlap.
- 62. Glucocorticoids • Cortisol (hydrocortisone), is the main glucocorticoid but small amounts of corticosterone and cortisone are also produced. • They are essential for life, regulating metabolism and responses to stress. • Secretion is controlled through negative feedback system involving the hypothalamus and anterior pituitary. • It is stimulated by ACTH from the anterior pituitary and by stress. • In non stressful conditions, secretion has marked circadia variations. • Glucocorticoids have widespread metabolic effects and these include: o Gluconeogenesis (formation of new sugar from, for example, protein) and hyperglycaemia (raised blood glucose level). o Lipolysis (breakdown of triglycerides into fatty acids and glycerol for energy production). o Stimulating breakdown of protein, releasing amino acids, which can be used for synthesis of other proteins, e.g. enzymes, or for energy (ATP) production? o Promoting absorption of sodium and water from renal tubules (a weak mineral corticoid effect).
- 63. • In pathological and pharmacological quantities glucoocorticoids also have other effects including: o Anti-inflammatory actions o Suppression of immune responses o Delayed wound healing
- 64. Mineralocorticoids (Aldosterone) • Aldosterone is the main mineralocorticoid. • Its functions are associated with the maintenance of water and electrolyte balance in the body. • Through a negative feedback system it stimulates the reabsorption of sodium (Na+) by the renal tubules and excretion of potassium (K+) in the urine. • Sodium reabsorption is also accompanied by retention of water and therefore aldosterone is involved in the regulation of blood volume and blood pressure too. • The blood potassium level regulates the amount of aldosterone produced by the adrenal cortex. • When the blood potassium level rises, more aldosterone is secreted. • Low blood potassium has the opposite effect. • Angiotensin also stimulates the release of aldosterone.
- 65. Renin-Angiotensin-Aldosterone System • When renal blood flow is reduced or blood sodium levels fall, the enzyme renin is secreted by kidney cells. • Renin converts the plasma protein angiotensinogen, produced by the liver, to angiotensin 1. • Angiotensin converting enzyme (ACE), formed in small quantities in the lungs, proximal kidney tubules and other tissues converts angiotensin 1 to angiotensin 2, which stimulates secretion of aldosterone. • It also causes vasoconstriction and increases blood pressure.
- 66. Sex Hormones • Sex hormones secreted by the adrenal cortex are mainly androgens (male sex hormones) and the amounts produced are insignificant compared with those secreted by the testes and ovaries in late puberty and adulthood.
- 69. Hormones Secreted by Endocrine Pancreas • The cells that make up the pancreatic islets (islets of Langerhans) are found in clusters irregularly distributed throughout the substance of the pancreas. • Unlike the exocrine pancreas, which produces pancreatic juice, there are no ducts leading from the clusters of islet cells. • Pancreatic hormones are secreted directly into the bloodstream and circulate throughout the body. • There are three main types of cells in the pancreatic islets: o α (alpha) cells, which secrete glucagon o β (beta) cells, which secrete insulin o Δ (delta) cells, which secrete somatostatin
- 70. • The normal blood glucose level is between 3.5 and 8 mmol/litre (63 to 144 mg/100 ml, blood glucose levels are controlled mainly by the opposing actions of insulin and glucagon, o Glucagon increases blood glucose levels. o Insulin reduces blood glucose levels. • The most numerous cells, types alpha and beta, secrete glucagon and insulin respectively. • Alpha cells tend to be concentrated at the periphery of islets, and beta cells more centrally. • A third type, the delta cell, secretes somatostatin and gastrin, and like alpha cells, is peripherally placed within the islets. • A minor cell type, the F cell, secretes pancreatic polypeptide (PP), which is stored in smaller secretory granules. • The autonomic transmitters acetylcholine (ACh) and noradrenalin affect islet cell secretion. • ACh augments insulin and glucagon release, noradrenalin inhibits glucose-induced insulin release and they may also affect somatostatin and PP secretion.
- 71. Insulin • The main function of insulin is to lower raised blood nutrient levels, especially glucose but also amino acids and fatty acids. • When these nutrients, especially glucose, are in excess of immediate needs insulin promotes their storage by: o Acting on cell membranes and stimulating uptake and use of glucose by muscle and connective tissue cells. o Increasing conversion of glucose to glycogen (glycogenesis), especially in the liver and skeletal muscles. o Accelerating uptake of amino acids by cells, and the synthesis of protein. o Promoting synthesis of fatty acids and storage of fat in adipose tissue (lipogenesis). o Decreasing glycogenolysis (breakdown of glycogen, into glucose). o Preventing the breakdown of protein and fat, and gluconeogenesis (formation of new sugar from, e.g., protein).
- 72. Glucagon • The effects of glucagon increase blood glucose levels by stimulating: o Conversion of glycogen to glucose in the liver and skeletal muscles (glycogenolysis). o Gluconeogenesis. o Somatostatin (GHRIH). • The effect of this hormone, also produced by the hypothalamus, is to inhibit the secretion of both insulin and glucagon in addition to inhibiting the secretion of GH from the anterior pituitary.
- 73. Local Hormones and Pineal Body • A number of body tissues secret hormones that act locally, these are Histamine, serotonin, and Prostaglandins. • Others are gastrointestinal hormones including Gastrin, Secretin and Cholecystokinin. • Histamine is secreted by mast cells and Basophils during inflammation. • It increases capillary permeability and causes vasodilatation. • Prostaglandins have a wide range of physiological effects in: o The inflammatory response o Potentiating pain o Regulating blood pressure o Blood clotting o Uterine contraction during labour
- 74. o Cause constriction or dilation in vascular smooth muscle cells o Cause aggregation or disaggregation of platelets o Sensitize spinal neurons to pain o Decrease intraocular pressure o Regulate inflammatory mediation o Regulate calcium movement o Control hormone regulation o Control cell growth o Acts on thermoregulatory center of hypothalamus to produce fever o Acts on mesangial cells in the glomerulus of the kidney, to increase glomerular filtration rate
- 75. Clinical Uses • Synthetic prostaglandins are used: o To induce childbirth (parturition) or abortion (PGE2 or PGF2, with or without mifepristone, a progesterone antagonist) o To prevent closure of patent ductus arteriosus in newborns with particular cyanotic heart defects (PGE1) o To prevent and treat peptic ulcers (PGE) o In pulmonary hypertension o In treatment of glaucoma (as in bimatoprost ophthalmic solution, a synthetic prostamide analog with ocular hypotensive activity) o To treat erectile dysfunction or in penile rehabilitation following surgery (PGE1 as alprostadil)
- 76. The Pineal Gland • This gland is located near the center of the brain in humans, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies join. • Its shape resembles a tiny pine cone (hence its name) and is stimulated by nerves from the eyes. • The pineal gland produces the serotonin derivative melatonin at night when it’s dark. • Melatonin a hormone that affects the modulation of wake/sleep patterns and seasonal functions, it promotes sleep. • It also affects reproductive functions by depressing the activity of the gonads. • Additionally, it affects thyroid and adrenal cortex functions • Because melatonin production is affected by the amount of light to which a person is exposed, this is tied to circadian rhythm(having an activity cycle of about 24hrs), annual cycles, and biological clock functions.
- 78. Thyroid and Parathyroid Gland • Structure of the Thyroid Gland • The thyroid is one of the largest endocrine glands in the body. • This gland is found in the neck inferior to (below) the thyroid cartilage (also known as the Adam's apple in men) and at approximately the same level as the cricoid cartilage. • The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings: (right lobe) and (left lobe), and is also connected with the isthmus. • The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath. • It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence or Adam's apple) and extends inferiorly to the fifth or sixth tracheal ring. • It is difficult to demarcate the gland's upper and lower border with vertebral levels because it moves position in relation to these during swallowing. • The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea, composed of an internal and external layer.
- 79. • The external layer is anteriorly continuous with the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the carotid sheath. • The gland is covered anteriorly with infrahyoid muscles and laterally with the sternocleidomastoid muscle. • On the posterior side, the gland is fixed to the cricoid and tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia to form the posterior suspensory ligament of berry. • Thyroid produces hormones that regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. • Iodine and tyrosine are used to form both thyroid hormones. • Production of thyroid hormones is controlled by the hypothalamus and pituitary.
- 80. Blood Supply • The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and sometimes by the thyroid artery, branching directly from the brachiocephalic trunk. • The venous blood is drained via superior thyroid veins, draining in the internal jugular vein, and via inferior thyroid veins, left brachiocephalic vein. • Lymphatic drainage passes frequently the lateral deep cervical lymph nodes and the pre and parathracheal lymph nodes. • The gland is supplied by sympathetic nerve input from the superior cervical ganglion and cervicothoracic ganglion of the sympathetic trunk, and by parasympathetic nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve.
- 82. PRODUCTION OF THYROID HORMONES AND ACTION. • The thyroid hormones are synthesized as a larger precursor molecules called thyroglobulin, the primary function of the thyroid is production of the hormones thyroxine(T4), triiodothyronine (T3) and calcitonin. • Up to 80% of the T4 is converted to T3 by the peripheral organs such as the liver, kidney and spleen. • T3 is about ten times more active than T4 • The major constituents of colloid • The release of T3 and T4 into the blood is regulated by thyroid stimulating hormone (TSH) from the anterior pituitary. • Secretion of TSH is stimulated by thyroid releasing hormone (TRH) from the hypothalamus and secretion of TRH is stimulated by exercise, stress, malnutrition, low plasma glucose and sleep. • Thyroxine (T4) is synthesized by the follicular cells from free tyrosine and on the tyrosineresidues of the protein called thyroglobulin (Tg). • Iodine is captured with the ‘iodine trap’ by the hydrogen peroxide generated by the enzyme thyroid peroxidase to T3.
- 83. • Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3. • Cells of the brain are a major target for the thyroid hormones T3 and T4. • Thyroid hormones play a particularly crucial role in brain maturation during fetal development. • In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. • Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. • Only the free fraction has hormonal activity.
- 84. T3 and T4 Regulation • The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH), released by the anterior pituitary (that is in turn released as a result of TRH release by the hypothalamus). • The thyroid and thyrotropes form a negative feedback loop. • TSH production is suppressed when the T4 levels are high, and vice versa. • The TSH production itself is modulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). • TSH production is blunted by somatostatin (SRIH), rising levels of glucocorticoids and sex hormones (estrogen and testosterone), and excessively high blood iodide concentration. • Secretion of T3 and T4 begins about the third month of fetal life and is increased at puberty and in women during the reproductive years, especially during pregnancy. • Otherwise, it remains fairly constant throughout life.
- 85. Calcitonin • An additional hormone produced by the thyroid contributes to the regulation of blood calcium levels. • This hormone is secreted by the parafollicular or C-cells in the thyroid gland. • Parafollicular cells produce calcitonin in response to hypercalcemia. • Calcitonin stimulates movement of calcium into bone, in opposition to the effects of parathyroid hormone (PTH). • However, calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids.
- 86. Significance of Iodine • Iodine is essential for the formation of the thyroid gland hormones, thyroxine (T4) and tri-iodothyronine (T3). • The body's main sources of iodine are seafood, vegetables grown in iodine-rich soil and iodinated table salt in the diet. • The thyroid gland selectively takes up iodine from the blood, a process called iodine trapping. • In areas of the world where iodine (essential for the production of thyroxine, which contains four iodine atoms) is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre. • The uptake mechanism with a large surplus of non-radioactive iodine, taken in the form of potassium iodide tablets. • While biological researchers making compounds labelled with iodine isotopes do this, in the wider world such preventive measures are usually not stockpiled before an accident, nor are they distributed adequately afterward.
- 87. • The use of iodised salt is an efficient way to add iodine to the diet. • It has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour or salt mandatory. • Potassium iodide and sodium iodide are the most active forms of supplemental iodine. • In humans, children born with thyroid hormone deficiency will have physical growth and development problems, and brain development can also be severely impaired, in the condition referred to as cretinism.
- 88. Functions of the Thyroid Hormones • Thyroid hormones enter the target cells and regulate the expression of genes in the nucleus, i.e. they increase or decrease the synthesis of some proteins including enzymes. • They combine with specific receptor sites and enhance the effects of other hormones, e.g. adrenaline (epinephrine) and noradrenaline (norepinephrine). • They increase the basal metabolic rate and heat production. • Regulating metabolism of carbohydrates, proteins and fats. • T3 and T4 are essential for normal growth and development, especially of the skeleton and nervous system. • Most other organs and systems are also influenced by thyroid hormones. • Physiological effects of T3 and T4 on the heart, skeletal muscles, skin, digestive and reproductive systems are more evident when there is underactivity or over- activity of the thyroid gland.
- 89. • It acts on bone and the kidneys to reduce the blood calcium (Ca2+) level when it is raised. • It reduces the reabsorption of calcium from bones and inhibits reabsorption of calcium by the renal tubules. • Its effect is opposite to that of parathyroid hormone, the hormone secreted by the parathyroid glands. • Release of calcitonin is stimulated by an increase in the blood calcium level. • This hormone is important during childhood when bones undergo considerable changes in size and shape.
- 90. Hyperthyroidism • Is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones (thyroxine or ‘T4’ and/or triiodothyronine or ‘T3’). • Hyperthyroidism is thus a cause of thyrotoxicosis the clinical condition of increased thyroid hormones in the blood. • Hyperthyroidism and thyrotoxicosis are not synonymous. • Thyroid hormone functions as a controller of the pace of all of the processes in the body. • This pace is called metabolism. • In excess, it both over stimulates metabolism and exacerbates the effect of the sympathetic nervous system, causing ‘speeding up’ of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). • These include fast heart beat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility (diarrhea), considerable weight loss and unusually low lipid panel (cholesterol) levels as indicated by a blood test.
- 91. • Hyperthyroidism usually begins slowly. • At first, the symptoms may be mistaken for simple nervousness due to stress. • If one has been trying to lose weight by dieting, one may be pleased with weight loss success until the hyperthyroidism, which has quickened the weight loss, causes other problems. • On the other hand, a lack of functioning thyroid tissue results in a symptomatic lack of thyroid hormone, termed hypothyroidism. • Hyperthyroidism often eventually leads to hypothyroidism. • Cretinism is a form of hypothyroidism found in infants.
- 92. Structure of the Parathyroid Gland. • Parathyroid glands are small flattened, oval lie external to the fibrous capsule on the medial half of the posterior surface of each lobe of the thyroid gland. • Most people have four parathyroid glands. • Approximately 5% of people have more; some have only two glands. • The two superior parathyroid glands are usually at the level of the inferior border of the cricoid cartilage. • The inferior parathyroid glands are usually near the inferior poles of the thyroid gland, but they may lie in a variety of positions. • The gland is composed of cuboidal epithelium that forms spherical follicles. • These secrete and store colloid, a thick sticky protein material.
- 93. Functions of the Parathyroid Gland • It produces hormone that regulation of serum calcium. • Its action is antagonistic to Calcitonin.
- 94. Regulation of Serum Phosphate • PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine. • However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. • In the intestines, which are mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D as is that of calcium. • The end result is a small net drop in the serum concentration of phosphate.
- 95. Vitamin D Synthesis • PTH increases the activity of 1-α-hydroxylase enzyme, which converts 25- hydroxycholecalciferol to 1, 25-dihydroxycholecalciferol, the active form of vitamin D. Regulation of PTH Secretion • Secretion of parathyroid hormone is chiefly controlled by serum [Ca2+] through negative feedback, which is achieved by the activation of calcium-sensing receptors located on parathyroid cells.
- 96. • Stimulators • Decreased serum [Ca2+]. • Mild decreases in serum [Mg2+]. • An increase in serum phosphate (Since increased phosphate will complex with serum calcium to form calcium phosphate, this causes the Ca sensitive receptors (CaSr) to think that serum Ca has decreased, as CaSR do not sense Calcium phosphate, thereby triggering an increase in PTH). Inhibitors • Increased serum [Ca2+]. • Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).
- 97. Clinical Significance • A high level of PTH in the blood is known as hyperparathyroidism. o If the cause is in the parathyroid gland it is called primary hyperparathyroidism. o The causes are parathyroid adenoma, parathyroid hyperplasia and parathyroid cancer. o If the cause is outside the gland, it is known as secondary hyperparathyroidism. o This can occur in chronic renal failure. o In secondary hyperparathyroidism, serum calcium levels are decreased, which causes the hypersecretion of PTH from the parathyroid glands. o PTH acts on the proximal tubules in the kidney to decrease reabsorption of Phosphate (increasing its excretion in urine, decreasing its serum concentration). o Note that in chronic renal failure, because the kidneys are failing they are unable to excrete phosphate in the urine, so in this case of secondary hyperparathyroidism, serum calcium will be decreased, but serum phosphate will be increased. • A low level of PTH in the blood is known as hypoparathyroidism. • Causes include surgical misadventure (eg inadvertent removal during routine thyroid surgery), autoimmune disorder, and inborn errors of metabolism.