-Ensherah Mokheemer -Talal Al-Zabin - 1 P a g e

Transcription

1 -3 -Ensherah Mokheemer -Talal Al-Zabin - 1 P a g e

2 In today s lecture we will start talking about the pathophysiology of the pituitary gland: Hypofunction of pituitary gland Panhypopituitarism : means decreased secretion of all pituitary gland hormones (anterior lobe and posterior lobe). Severe anterior pituitary deficiency: deficiency of all anterior pituitary hormones Moderate anterior pituitary deficiency: deficiency in all anterior pituitary hormones except STH it is normal Mild anterior pituitary deficiency: from the anterior pituitary hormones only, Gonadotropins hormones are deficient, the others are normal Note that in all cases gonadotropins hormones are deficient, why is that? Out of the hormones of the pituitary gland, Gonadotropins are the hormones secreted with the least percentage (3%-5%) and if you take a section in the pituitary gland you will find the distribution of gonadotropin secreting cells (Gonadotrophs) is the least. 1-Panhypopituitarism: Panhypopituitarism: pan means all, it is a condition of inadequate or absent production of all pituitary hormones (posterior and anterior). Etiology: -Extensive destructive tumour (usually Craniopharyngioma). -Postsurgical -Granuloma or trauma. Remember: The Hormones of the pituitary gland Anterior Lobe: Tropic: ACTH, FSH, LH, TSH Non-tropic: GH and prolactin. Posterior Lobe Oxytocin. * ADH (vasopressin). *Oxytocin works on delivery and milk ejection, but there are other factors involved in milk ejection and delivery, so there are no major problems that occur due to oxytocin deficiency. Manifestation: Hormones of the Posterior pituitary: 2 P a g e

3 -Antidiuretic hormone deficiency: ADH deficiency causes central diabetes insipidus which is a condition characterized by large amount of diluted urine and increased thirst. What ADH do is simply increase water reabsorption and eventually decreases the urine volume and increase its osmolarity so in the absence of adequate amount of ADH urine osmolarity will decrease (Diluted urine) and urine volume will increase (loss of water as urine will increase leading to Polydipsia Increased thirst ). The colour of the urine in case of diabetes insipidus is pale because it is diluted as for the urine but in case of diabetes mellitus it has normal urine colour varying from light yellow to dark yellow depending on fluid intake. -Oxytocin deficiency: In the deficiency of oxytocin, delivery occurs but it'll be much more difficult. Also, milk production is not much affected because of the presence of other factors affecting milk ejection and delivery. Hormones of the Anterior pituitary: The normal function of ADH Water deprivation Increase plasma Increase secretion of ADH from posterior pituitary Increases water permeability of late distal tubule of the kidney Increase water reabsorption Increase urine osmolarity and decrease urine volume -Gonadotropins deficiency: the function of the primary sexual organs ( ovaries and testis), which is the production of ova and sperms respectively and the secretion of hormones, is affected by the deficiency of the gonadotropins. In Males: decreased libido (sexual desire), Aspermia, Loss of some facial and body hair. In females: Decreased libido, Amenorrhea (no menstrual cycle). Recall that Gonadotropins includes: *Follicle-stimulating hormone (FSH): stimulates development of ovarian follicle and regulates spermatogenesis in the testis. *Luteinizing Hormone(LH): causes ovulation and formation of the corpus luteum in the ovary, stimulates production of estrogen and progesterone by the ovary, stimulates testosterone production by the testis. 3 P a g e

4 Child: Delayed puberty. -TSH deficiency: Hypothyroidism. -ACTH deficiency: Adrenal cortical insufficiency. The production of glucocorticoids and androgens is affected, especially cortisol. TSH (Thyroid stimulating hormone): stimulates the production of thyroid hormones. ACTH (Adrenocorticotropic hormone): stimulates the production of glucocorticoids and androgens by adrenal cortex. -MSH (Melanocyte Stimulating Hormone): its deficiency causes pallor (paleness). - Growth Hormone (somatotropin): Its deficiency causes dwarfism (short stature). The individuals do not grow properly and become dwarfs. Usually their mentality is normal, but their fertility might be sometimes affected; they are sometimes infertile. They also suffer from muscle loss, microsplanchnia (the abdomen is small compared to the thorax) and hypoglycaemia. 2-severe anterior pituitary deficiency similar to panhypopituitarism, except that the hormones of the posterior pituitary are normal. All hormones of the anterior pituitary are deficient. 3-Moderate anterior pituitary deficiency Growth hormone is normal, MSH and ACTH are partially deficient, Gonadotropins and TSH are deficient. 4 P a g e

5 4- Mild anterior pituitary deficiency All the hormones of the anterior pituitary are normal except gonadotropins (FSH & LH). Over secretion of Growth Hormone - Giantism (Gigantism): If the over secretion occurs before adolescence, all body tissue will grow rapidly including the bone because the epiphyses of the long bone have not fused with the shaft. 1-Their height is 8-9 feet (1 foot=30.5cm); they are more than 2.5m tall. 2-The giants have hyperglycemia (GH increases glucose level in blood), 10% develops diabetes mellitus. 5 P a g e

6 EXTRA: How can giantism cause diabetes mellitus? Because of hyperglycemia, the beta cells of the islets of Langerhans in the pancreas become overactive and thus they become prone to degenerate. Remember that beta cells produce insulin and Diabetes is due to the pancreas not producing enough insulin so by the degeneration of beta cells no enough insulin will be produce and diabetes mellites develops. 3-If the giants remain without treatment they will develop panhypopituitarism, this is because the gigantism is usually caused by a tumor of the pituitary gland that grows until the gland is destroyed. ** Their extremities have normal proportions, but they are very tall. - Acromegaly: if the over secretion occurs after adolescence, after the fusion of the epiphyses of the long bone have fused with the shaft. The person cannot grow taller, but the bone can become thicker and the soft tissue can continue to grow. 1-Enlargment marked in the small bones of the hands and feet and in the membranous bones, including the cranium, nose forehead, supraorbital ridge, the lower jaw bones and portions of the vertebrae. 2- Many soft tissue or organs like the liver, the tongue and especially the kidneys, become greatly enlarged. Adrenal Glands There are two adrenal glands: left and right. They lie in the superior pole of the two kidneys, each gland is composed of two major parts the adrenal medulla and the adrenal cortex. The blood supply of these glands comes directly from the aorta, which indicates the importance of these gland. ** The adrenal glands have the greatest blood supply rates per gram of tissue of any organ. **If we remove the adrenal glands the person does not survive but one gland is sufficient. 6 P a g e

7 The regulation of cortisol secretion by the hypothalamus-pituitaryadrenal axis. - ACTH (Adrenocorticotropic hormone), an anterior pituitary hormone, stimulates growth of the adrenal cortex and the synthesis and secretion of all its hormones. The main target hormone of ACTH is cortisol. ACTH stimulates desmolase enzyme that converts cholesterol to pregnenolone thus increasing the synthesis of cortisol - Foetus ACTH synthesis and secretion begins just before the development of the adrenal cortex. - The regulation of ACTH secretion is among the most complex of all the pituitary hormones. Although the mechanisms for each form of control are not completely clear, the CRH and ADH are the main stimuli for ACTH secretion. ACTH secretion responds most strikingly to stressful stimuli of all types, a response that is critical for survival. - ACTH has extra-adrenal actions like: lipolysis and MSH-like action. -ACTH regulates the growth and secretion of the adrenal cortex. Let s discuss the regulation of cortisol secretion by the hypothalamuspituitary-adrenal axis: -ACTH (from the anterior pituitary gland) stimulates cortisol secretion (from the adrenal gland), on the other hand ACTH secretion is controlled by corticotropin releasing hormone (RCH) from the hypothalamus. * CRH and ADH are the main stimuli for ACTH secretion. ACTH secretion responds most strikingly to stressful stimuli of all types, a response that is critical for survival: 7 P a g e

8 Pain stimuli caused by physical stress or tissue damage are transmitted first upward through the brain stem and eventually to the median eminence of the hypothalamus and then carried to the anterior pituitary gland where it induces ACTH secretion. The main effect of ACTH on the adrenocortical cells is to activate adenylyl cyclase in the cell membrane. This induces the formation of camp, which activates intracellular enzymes that causes the formation of adrenocortical hormones. One of the moist important intracellular enzymes to be activated is the desmolase, which causes the conversion of cortisol to pregnenolone. This conversion is the rate-limiting step for all the adrenocortical hormones synthesis. Stress stimulates Hypothalamus CRH Anterior pituitary ACTH Adrenal gland ** important: only Cortisol exhibits negative feedback on both the hypothalamus and the pituitary gland. Adrenocortical hormones mainly cortisol - As mentioned before the adrenal gland is composed of two major parts and these parts differ in their embryology, histology, and physiology, their total weight is 6-10g. The Adrenal medulla (20%): the central part of the gland is functionally related to the sympathetic nervous system. It secretes the hormones epinephrine and norepinephrine (catecholamines) in response to sympathetic stimulation. The Adrenal cortex (80%): secretes an entirely different group of hormones called corticosteroids, these hormones are synthesised form steroid cortisol. The adrenal cortex hormones are essential for life because it: Controls Na+, k+ and H2O metabolism Controls carbohydrate, fat and protein metabolism and mobilization for energy. Participates in responses of stresses of various kinds. 8 P a g e

9 The adrenal cortex is composed of 3 zones, and each zone produces specific hormones: 1-Glomerulosa (12%): It produces several hormones collectively known as mineralocorticoids. The most potent hormone of these is aldosterone. From their name, these hormones only function on the metabolism of minerals. 2-Fasciculata (65%): This zone produces a group of hormones called glucocorticoids which function on glucose metabolism. The most potent glucocorticoid is cortisol. This zone also produces a small amount of androgens and estrogens. 3- Reticularis (23%): It mainly produces androgens and estrogens, but it also produces small amounts of cortisol. The adrenal reticularis does not develop properly until the age of 6-8yrs. In the adult, the cells of the glomerulosa migrate down to the reticularis and they change their shape and function while migrating. 9 P a g e

10 Explanation of this figure: (a) Glucocorticoid activity: even aldosterone (a mineralocorticoid) plays a role in glucose metabolism. (b) Mineralocorticoid activity: In addition to aldosterone, cortisol (a glucocorticoid) plays a role in the metabolism of minerals (c) Secretion rate: the secretion rate of cortisol is higher. (d) The contribution of glucocorticoid activity: cortisol has the main role and aldosterone has some contribution (e) Mineralocorticoid contribution: cortisol also contributes in mineralocorticoid activity, but its relative contribution is much more than that of aldosterone, because it has a higher secretion rate (according to c), the amount of cortisol secreted is more than the amounts of aldosterone. Glucocorticoid activity: means which one is more potent as a glucocorticoid? it is the cortisol. Mineralocorticoid activity: This means which one of them is more potent as a mineralocorticoid? It is aldosterone. Secretion rate: Here we compare between the rate of secretion for both of them and we find that cortisol is secreted in a much higher rate than aldosterone, (blood concentrations of cortisol are something like fold higher than aldosterone). Glucocorticoid contribution: This means how much both (cortisol and aldosterone) contribute to the amount of glucocorticoids, and from this figure we find cortisol has a higher contribution. (the amount of cortisol that works as a glucocorticoid is higher than the amount of aldosterone that works as a glucocorticoid) Mineralocorticoids contribution: This means how much both (Cortisol and aldosterone) contribute to the amount of mineralocorticoids, and cortisol was found to be a higher contributor. 10 P a g e

11 The cortisol contributes more than aldosterone in both glucocorticoids and mineralocorticoids that is because it is secreted in much higher rate (more than 200 folds) so its levels will always be much greater than aldosterone s levels. Note that in contribution we take the secretion rate into consideration, not only the potency like in activity. Rhythm of ACTH and cortisol throughout the day: *Recall: the main target hormone of ACTH is cortisol; when ACTH level changes, cortisol level changes. Cortisol is relatively high in the morning but low in the afternoon and early evening. ACTH and cortisol show circadian rhythm as well as pulsatile rhythm. The synthesis of the adrenal cortical hormones - All the adrenal cortical hormones are steroids and are synthesized from cholesterol. - They are synthesized in many steps; many enzymes are needed. - When these hormones, are produced they are released immediately into the blood. This means that any need requires new synthesis. -The adrenal cortex produces steroids: Recall that steroid hormones are: Adrenocortical hormones, sex hormones in both females and males and vitamin D. 11 P a g e

12 that regulates Na+ and k+ balance (Mineralocorticoids). That regulates glucose balance (glucocorticoids) Small amounts of sex steroid hormones. Sometimes there is a problem in the last step of cortisol production which leads to increase in the level of corticosterone. -when the adrenal cortex hormones are produced, they are not stored in the gland, rather they are released immediately and this means that in any need of new hormones, new synthesis of these hormones is required because there are no hormones stored in the adrenal cortex. 90% of cortisol is bound to Corticosteroid- binding protein and 6% binds with albumin, and the free functional part is only 4%. 12 P a g e

13 Being a steroid allows the Cortisol to act on all the systems of the body. The main Functions of cortisol are: 1. Production of glucose from non-carbohydrate sources. 2. Facilitates fat mobilization. 3. Increase the response of blood vessels to catecholamines. 4. Modulate CNS function - The most important function of cortisol is that it facilitates the production of glucose from non-carbohydrate sources. This makes cortisol essential for life for humans and animals especially during fasting; it has a role in the Defence against hypoglycaemia. This means that humans and animals cannot fast in case of cortisol deficiency. - Cortisol affects glycogenolysis but in permissive interaction, it facilitates the action of glucagon, this means that glucagon causes 13 P a g e

14 glycogenolysis by the help of cortisol, this is like the relation between adrenaline and thyroxin on the fat cell (permissive relation) -Hypoglycemia occurs because of the deficincy of cortisol, hypoglycemia is a kind of stress (danger). -Cortisol binds very well to the aldosteron receptors to produce mineral corticoid activity. But there is an enzyme in the kidney that inactivates cortisol. In this case cortisol does not function adequetly as mineralcorticoid. 14 P a g e

15 Cortisol is important even during fetal life. It is essential for the normal development of the fetus; it is involved in: 1. Production of surfactant from type II cells of the alveoli of the lung-a lack of which leads to the respiratory distress syndrome in newborn infants. Extra: Surfactant are phopholipids that lubricates the function of the lung and they are secreted by the type II alveolar epithelial cells in response to beta adrenergic stimulation and the synthesis is increased by corticosteroids. Being a detergent, surfactant lines the air-fluid interface converting it into an air-surfactant interface. This allows surfactant to serve three functions in the respiratory system: Reduction of surface tension Maintaining alveolar stability Reduction of ultra-filtration 2. Development of hypothalamic function and of the thyroid-pituitary axis. 3. The sequential changes of placental structure and in the ionic composition of amniotic and allantoic fluids during development. 4. They are most important in the initiation of the endocrine changes of the fetus and mother which are responsible for parturition. 5. The development of hepatic enzymes, including those involved in gluconeogenesis. 6. Induction of thymic involution. -cortisol is considered as a magical drug since it works on all body systems and is used in many diseases; from skin to cardiovascular diseases. However, it sometimes does not function in some people. If it finds the receptor it functions, if not it doesn't function. - people who have cortisol as drug they look obese because it retains minerals,and also increases apetite. 15 P a g e

16 There are natural as well as synthetic glucocorticoids: Cortisol: very potent, accounts for about 95% of all glucocorticoid activity. Corticosterone: provides about 4 per cent of total glucocorticoid activity but much less potent than cortisol. Any problem in the last step of the synthesis of cortisol, corticosterone level increases. Cortisone: synthetic, almost as potent as cortisol. Methyl prednisone: synthetic, five times as potent as cortisol. Dexamethasone: synthetic, 30 times as potent as cortisol. The End Sorry for any mistake Good luck 16 P a g e