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Prolactin (PRL) PRL is a hormone secreted by the lactotrophs, present in the anterior pituitary gland, and its secretion is under the inhibitory control of hypothalamic dopamine that reaches the anterior pituitary gland through the portal circulation via the pituitary stalk. *Physiologic Effects of...

Prolactin (PRL) PRL is a hormone secreted by the lactotrophs, present in the anterior pituitary gland, and its secretion is under the inhibitory control of hypothalamic dopamine that reaches the anterior pituitary gland through the portal circulation via the pituitary stalk. *Physiologic Effects of Prolactin: Prolactin, in combination with estrogens and Progesterone initiates and maintains lactation. *Prolactin has two major roles in milk production: 1- Prolactin induces growth of the mammary gland. 2- Prolactin stimulates lactogenesis or milk production after giving birth. *Control of Prolactin Secretion The hypothalamus suppresses prolactin secretion from the pituitary gland. Dopamine serves as the major prolactin-inhibiting factor or brake on prolactin secretion. *Disease States of Prolactin Excessive secretion of prolactin - hyperprolactinemia -is a relatively common disorder in humans. Hyperprolactinemia is a condition of elevated prolactin levels in blood above the normal range which could be physiological, pharmacological and pathological, or idiopathic in origin. Causes: ✓ Physiological: pregnancy and lactation and mammary stimulation. ✓ Pharmacologic: neuroleptic and antipsychotic medications (chlorpromazine, risperidone, haloperidol), antidepressants, opioids, cocaine, antihypertensive medications (verapamil, methyldopa), drugs that act in the gastrointestinal tract (metoclopramide, domperidone), and the use of estrogens.  ✓ Associated with systemic diseases: kidney and liver failure. ✓ Associated with endocrinological diseases: primary hypothyroidism, polycystic ovarian syndrome (PCOS), and Addison’s and Cushing’s diseases. ✓ Other tumors of the hypothalamic-pituitary region ✓ The most common cause of hyperprolactinemia is a prolactinoma, a benign (noncancerous) prolactin- releasing tumor (pituitary gland tumors). ✓ Idiopathic. *Common manifestations of hyperprolactinemia in Women ✓ Menstrual irregularities (amenorrhoea or oligomenorrhoea), infertility, decreased libido. ✓ Galactorrhea (excessive or spontaneous secretion of milk). *Disease state in Men In males, hyperprolactinaemia causes ✓ Hypogonadism manifesting with reduced libido, erectile dysfunction, and impaired spermatogenesis. ✓ Gynaecomastia (secondary to hypogonadism) and galactorrhoea occur rarely. ✓ Anaemia, decreased energy and muscle mass may be also present as secondary manifestations of hypogonadism. Case 2: A 23-year-old woman has experienced recent onset of a spontaneous, bilateral breast discharge and gradual cessation of menses. She reports normal growth and development and has never been pregnant. Questions & answers: 1. What conditions could be causing her symptoms? This woman is suffering from hyperprolactinemia (which is characterized by bilateral breast discharge and irregular menstrual cycle) which means that there is a high level of prolactin secretion in blood. 2 - What medical conditions (other than a prolactinoma) are associated with hyperprolactinemia? - Hypothyroidism (due to TSH release from pituitary gland as a response of low thyroxin level and consequently, prolactin hormone increases). - Polycystic ovary syndrome. - Liver failure and renal failure. 3 - Which medications raise prolactin? -some drugs as: *antidepressants as (Fluoxetine). *antipsychotics as (phenothiazine - Butyrophenone - Risperidone). *Anti-hypertensive drugs. *prokinetics as (Metoclopramide). 4 - How would your thinking change if she had galactorrhea but normal levels of prolactin? - Idiopathic galactorrhea , it means that the breast tissues is particularly sensitive to prolactin more than normal , which in turn leads to galactorrhea even with normal level of prolactin in blood Case 12: A 35 years old man admitted to out-patient clinic with decreased sex drive, decreased sperm production impotence and breast enlargement but without milk secretion. 1- What is the metabolic disorder underlying these conditions? Explain your answer? Hyperprolactinemia. (Decreased sex desire.-Decreased sperm count.-Breast enlargement). 2- Causes of these disorders? Physiologic causes: ✓ (Pregnancy, Lactation, Sleep, Stress). Pathologic causes: ✓ The most common cause of hyperprolactinemia is a prolactinoma, a benign (noncancerous) prolactin- releasing tumor (pituitary gland tumors). ✓ Hypothyroidism. ✓ Certain medications (Anti-dopaminergic drugs such as metoclopramide, Antidepressant drugs, Antipsychotic drugs, Antihypertensive drug , estrogen). 3-What is the hormone involved? Prolactin 4-Physiological functions of this hormone? Physiologic Effects of Prolactin: Prolactin, in combination with estrogens and Progesterone initiates and maintain lactation. Prolactin has two major roles in milk production: 1- Prolactin induces growth of the mammary gland. 2- Prolactin stimulates lactogenesis or milk production after giving birth. 5- Regulation of secretion of this hormone? Control of Prolactin Secretion The hypothalamus suppresses prolactin secretion from the pituitary gland. Dopamine serves as the major prolactin-inhibiting factor or brake on prolactin secretion. Thyroid gland Introduction: The thyroid is part of the endocrine system, inside your neck ,located just in front of your trachea, which is made up of glands that produce, store, and release Hormones into the bloodstream. Thyroid gland is responsible for production of: -Triiodothyronine (T3) -Thyroxine (T4) Physiological functions of the hormone: Thyroid hormones are responsible for: Increasing the basal metabolic rate. Inducing the lipolysis or lipid synthesis depending on the metabolic status. Stimulating the carbohydrate metabolism. Affecting the catecholamines (permissive effect by increasing the expression of beta receptors to increase heart rate, stroke volume, cardiac output and contractility.  Stimulating bone growth in children in addition to the growth hormone. Affecting fertility, ovulation and menstruation. Stimulating the respiratory centers and increasing oxygenation due to increased perfusion. Increasing development of type 2 muscle fibers. Synthesis and regulation :- Synthesis and release of T3 and T4 are stimulated by thyroid stimulating hormone) TSH (released from pituitary gland.TSH secretion is under control of thyrotropin releasing hormone )TRH (which is produced in the hypothalamus. Metabolic disorders of thyroid glands: A- Hyperthyroidism B- Hypothyroidism A-Hypertyhrodism:- It is over activity of the thyroid gland that leads to high levels of thyroid hormones (triiodothyronine (T3) and thyroxine (T4(and speeding up of vital body functions. Symptoms: ▪ Losing weight without trying. ▪ Fast heartbeat (tachycardia) and Irregular heartbeat (arrhythmia). ▪ Increased hunger, Sweating and Tiredness. ▪ Nervousness, anxiety and irritability. ▪ Tremor in the hands and fingers. ▪ Increased sensitivity to heat. ▪ Enlarged thyroid gland, sometimes called a goiter. ▪ Muscle weakness, Sleep problems and Warm, moist skin  ▪ Causes:- 1-Graves disease (it is often hereditary) :- It is an autoimmune disorder caused by an abnormal antibody in the blood that causes the immune system to attack the thyroid gland. That prompts the thyroid to make too much thyroid hormone. It is the most common cause hyperthyroidism. 2- Thyroiditis (it is often temporary) :- the thyroid gland becomes inflamed (the reason for it is unclear may be due to autoimmune disorder). When a woman’s thyroid becomes inflamed after having a baby causes (Postpartum thyroiditis ). Inflammation can cause extra thyroid hormone stored in the thyroid gland to leak into the bloodstream and cause symptoms of hyperthyroidism. 3-Toxic nodular goiter also called (multinodular goiter ) Thyroid nodules are caused by an overgrowth of cells in the thyroid gland (goiter). These growths can be: Not cancer (benign), thyroid cancer(malignant) and Fluid-filled 4-Too much iodine:- thyroid gland uses iodine to make thyroid hormone. 5-Over stimulation due to an overactive pituitary gland Overproduction of TSH. 6-Too much thyroid hormone medicine :- some people who take thyroid hormone medicine for hypothyroidism may take too much. Diagnosis: 1-Blood tests:- to check the level of thyroid hormones. If you have thyrotoxicosis, the T3 and T4 levels will be high, while the thyroid-stimulating hormone (TSH) levels will be low. 2-The radioactive iodine uptake test: - checks how well your thyroid absorbs the radioactive iodine. The high radioactive iodine uptake means excessive production of T4. You may develop thyroid nodules and Graves’ disease. The low radioactive iodine uptake means there is a leakage of T4 into your bloodstream from thyroiditis. 3-Thyroid scan:- to look for inflammation, nodules, goiter, and thyroid cancer by injecting radiotracer or radioactive liquid into your veins. TSH: - measures thyroid-stimulating hormoneT4 and T3. TSI: - measures thyroid-stimulating immunoglobulin. Antithyroid antibody test: - measures antibodies (markers in the blood). 4-Thyroid ultrasound:- to determine if you have nodules on the thyroid. B-Hypothyroidism:- Hypothyroidism, also called underactive thyroid disease, is a common disorder. With hypothyroidism, your thyroid gland does not make enough thyroid hormone. Symptoms:- - Increase cold sensitivity. - Hoarseness in voice. - Puffy face and eyes. - eye lids drop. - Enlarged thyroid gland(goiter) & weight gain. - Slowed heart rate. Causes:- The most common cause of hypothyroidism is Hashimoto’s thyroiditis. is an autoimmune disorder. With Hashimoto’s, your body produces antibodies that attack and destroy the thyroid gland. Thyroiditis is an inflammation of the thyroid gland that may also be caused by a viral infection. - Primary : Autoimmune disease. Iodine deficiency. Iodide excess. Genetic abnormality. - Secondary : Drugs induced Hypothyroidism ( Amiodarone, Lithium Adenoma Pituitary destruction Ablative therapy - Tertiary : Hypothalamic disfunction. Diagnosis:- ▪ If you have symptoms of hypothyroidism, your doctor will order blood tests to check hormone levels. These may include: ▪ Thyroid-stimulating hormone (TSH) ▪ T4 (thyroxine) ▪ A low level of thyroxine and high level of TSH indicate an underactive thyroid. ▪ That’s because your pituitary produces more TSH in an effort to stimulate your thyroid gland into producing more thyroid hormone. Treatment:- ▪ Standard treatment for hypothyroidism involves daily use of the synthetic thyroid hormone levothyroxine (Levo-T, Synthroid, others). This oral medication restores adequate hormone levels, reversing the signs and symptoms of hypothyroidism. Diabetes mellitus Definition: Metabolic disorder characterized by hyperglycemia due to an absolute or relative lack of insulin or to a cellular resistance to insulin. Main classification of diabetes.  T1DM is characterized by the destruction of beta cells in the pancreas, it’s due to an autoimmune disease, so insulin becomes absent or extremely low. It affects children mainly, treated by insulin.  T2DM involves a more insidious onset where an imbalance between insulin levels and insulin sensitivity causes a functional deficit of insulin. Insulin resistance is multifactorial but commonly develops from obesity and aging. It affects mainly middle-aged and older adults who have prolonged hyperglycemia due to poor lifestyle and dietary choices, treated by oral hypoglycemic drugs. Other types of diabetes. Neonatal diabetes: This is a rare form of diabetes that occurs within the first six months of life. It’s also a form of monogenic diabetes. About 50% of babies with neonatal diabetes have the lifelong form called permanent neonatal diabetes mellitus. Gestational diabetes: is hyperglycaemia with blood glucose values above normal but below those diagnostic of diabetes. Gestational diabetes occurs during pregnancy. ▪ Women with gestational diabetes are at an increased risk of complications during pregnancy and at delivery. ▪ These women and possibly their children are also at increased risk of type 2 diabetes in the future. ▪ Gestational diabetes is diagnosed through prenatal screening, rather than through reported symptoms. Diabetes insipidus. your blood glucose levels are normal, but your kidneys can’t properly concentrate urine. Although both conditions can increase thirst, intake of liquids, and urination, they are not related. Risk factors of diabetes: Symptoms of diabetes. Complications of diabetes: Management and Prevention: Hormone involved in diabetes: Insulin hormone which is secreted from beta cells in the pancreas and secreted in the blood to reduce the blood glucose level by taking it into the cells for storage or producing energy. Biosynthesis of insulin hormone:  Secretion of insulin hormone: Insulin secretion stimulated by glucose is a complex process of signal transduction in beta cells, comprised of proximal events which include glucose internalization through glucose transporters (GLUT) and its catabolism through glycolysis, Krebs cycle, and oxidative phosphorylation, leading to a rise in ATP/ADP ratio, and by distal events, which include the activation of different ionic channels. Hypoglycemia Definition : ▪ blood sugar (glucose) is below 70 mg/dL. It needs to be treated quickly to stop it getting worse, but you can usually treat it yourself. ▪ affects people with diabetes who take insulin or some other diabetes medicines. ▪ It's rare in people without diabetes. symptoms: ▪ feeling hungry ▪ feeling dizzy ▪ feeling anxious ▪ sweating ▪ heart palpitations ▪ weakness ▪ blurred vision If you have severe low blood sugar you may: ▪ have a seizure or fit ▪ become unconscious / coma How to treat low blood sugar yourself? ▪ Eat or drink something that will raise your blood sugar quickly. ▪ Check your blood sugar after 10 to 15 minutes. ▪ If your blood sugar is still below 70 mg/dL, have another sugary drink or snack, and check again after10 minute How to treat severe low blood sugar ? ▪ Do not give them any food or drink as they will not be able to swallow safely. ▪ Give them a glucagon injection ▪ If they start to recover within 10 minutes of having a glucagon injection and can swallow safely, give them some food or drink that will raise their blood sugar Hormones involved: glucagon hormone secreted from alpha cells of pancreas and insulin hormone. ▪ Biochemical mechanisms of glucose regulation in the fasting and fed states. First, during fasting state: ▪ As blood glucose levels fall during fasting, the pancreas secretes increased amounts of glucagon as a response. ▪ Glucagon binds to glucagon receptors at the liver to trigger a cyclic AMP cascade that eventually activates glycogen phosphorylase. ▪ Glucagon cause the liver to break down glycogen and release the glucose back into the bloodstream Second, during fed state : ▪ In the fed state, or postprandial, elevated glucose levels trigger the release of insulin from the pancreas. ▪ As insulin levels rise, there is an increase in glucose uptake, oxidation, and storage in peripheral tissues as well as increases in other anabolic pathways. Diabetes insipidus Common types of diabetes Diabetes Mellitus Diabetes Innocence Diabetes Insipidus 1-diabetes mellitus a chronic disease associated with abnormally high levels of glucose in the blood. There are two main types of diabetes mellitus:  1. diabetes innocence A rare condition in which glucose is excreted in the urine despite normal blood glucose levels. Glucose should only be excreted in the urine when there are abnormally elevated levels of glucose in the blood. However, in those with renal glycosuria, glucose is abnormally elevated in the urine due to improper functioning of the renal tubules lowering the renal threshold for glucose 2. diabetes insipidus is a rare disorder that causes the body to produce too much urine. Patients with diabetes insipidus can make up to 16L of urine a day. Patients with this disorder need to urinate frequently (polyuria). They also feel thirsty all the time and drink lots of liquids (polydipsia). Antidiuretic hormone: 1. cyclic poly peptide containing 8 amino acids 2. It’s secreted by the posterior lobe of the pituitary gland. It is actually synthesized in the cell body of neurons of the hypothalamus and transported down their axons to the posterior pituitary where it is secreted. physiologic effects of antidiuretic hormone 1. effect on kidney The single most important effect of antidiuretic hormone is to conserve body water by reducing the output of urine. Mechanism: ADH binds to receptors in the distal or collecting tubules of the kidney and promotes reabsorption of water back into the circulation. 2-Effect on vascular system High concentrations of antidiuretic hormone cause widespread constriction of arterioles, which leads to increased arterial pressure. 1. what is the metabolic disorder underlying these conditions? explain your answer? Diabetes insipidus. Patient suffer from symptoms of diabetes Insipidus Which are: 1) Extreme thirst 2) Polyuria 3) Colorless urine 4) Waking frequently through the night to urinate 5) Dry skin 6) Weak muscles. Normal blood glucose and no glucose in urine so it is not diabetes mellitus and not Diabetes innocence 2. causes of disorder? Primary Hypothalamic ("central") diabetes insipidus: It results from a deficiency in secretion of antidiuretic hormone from the posterior pituitary. Causes of this disease include head trauma, and infections or tumors involving the hypothalamus. Hereditary Nephrogenic diabetes insipidus: It occurs when the kidney is unable to respond to antidiuretic hormone. Most commonly, this results from some type of renal disease. 2. mechanism of regulation of Antidiuretic hormone Anti diuretic hormone isn’t regulated by classic feedback inhibtion like most hormones. The most important variable regulating antidiuretic hormone secretion is PLASMA OSMOLARITY, or the concentration of solutes in blood. Osmolarity is sensed in the hypothalamus by neurons known as an OSMORECEPTORS, and those neurons, in turn, simulate secretion from the neurons that produce antidiuretic hormone. When plasma osmolarity is below a certain threshold, the osmoreceptors are not activated and antidiuretic hormone secretion is suppressed. When osmolarity increases above the threshold, osmoreceptors stimulate neurons that secrete the antidiuretic hormone. Blood pressure and baroreceptors also control ADH secretion. 4-What is the test that could be done to prove diabetes insipidus? Water deprivation test Note: Normal person will respond to the test by secreting ADH and reduce urine output.  Hepatitis A (infectious hepatitis) Hepatitis A is a highly contagious liver infection caused by the hepatitis A virus. The virus is one of several types of hepatitis viruses that cause inflammation and affect your liver's ability to function. ▪ Hepatitis A Symptoms Hepatitis A signs and symptoms typically don't appear until you've had the virus for a few weeks. But not everyone with hepatitis A develops them. If you do, hepatitis signs and symptoms can include: Fatigue Sudden nausea and vomiting Abdominal pain or discomfort, especially on the upper right side beneath your lower ribs (by your liver) Clay-colored bowel movements Loss of appetite Low-grade fever Dark urine Joint pain Yellowing of the skin and the whites of your eyes (jaundice) Intense itching If you're over age 50 or have a long-term liver disease, you may have a more severe case of the disease called fulminant hepatitis A infection. You could have symptoms like: Spontaneous bleeding or easy bruising Confusion and changes in alertness Liver function that gets worse Yellowing of the skin and eyes that gets worse ▪ Hepatitis A Causes. You can catch the disease by drinking water or eating food that's been contaminated by someone with the virus. You can also get hepatitis A if you: ✓ Eat fruits, vegetables, or other foods handled or prepared by a person who has the virus. ✓ Eat raw shellfish harvested from water where the virus lives. ✓ Swallow contaminated ice. ✓ Have sex with someone who has it. ✓ Touch your mouth after touching a contaminated object. ▪ Hepatitis A Risk Factors ✓ Travel or work in areas of the world where hepatitis A is common ✓ Attend child care or work in a child care center ✓ Live with another person who has hepatitis A ✓ Are a man who has sexual contact with other men ✓ Have any type of sexual contact with someone who has hepatitis A ✓ Are HIV positive ✓ Are experiencing homelessness ✓ Have a clotting-factor disorder, such as hemophilia ✓ Use any type of illegal drugs (not just those that are injected) ▪ Hepatitis A Diagnosis Your doctor will first ask about your symptoms and check for high levels of liver enzymes in your blood. Then, they’ll do more blood tests to look for: IgM (immunoglobulin M) antibodies. Your body makes these when you’re first exposed to hepatitis A. They stay in your blood for about 3 to 6 months. IgG (immunoglobulin G) antibodies. These show up after the virus has been in your body for a while. You may have them all your life. They protect you against hepatitis A. If you test positive for them but not for IgM antibodies, it means you had a hepatitis A infection in the past or had vaccinations to protect against it. Hepatitis A Treatment No medication can get rid of the hepatitis A virus once you have it. Your doctor will treat your symptoms -- they may call this supportive care -- until it goes away. They’ll also do tests that check how well your liver is working to be sure your body is healing like it should. ✓ You can take these steps to make yourself more comfortable: ✓ Get some rest. You’ll probably feel tired and sick and have less energy than usual. ✓ Try to keep food down. The nausea that sometimes comes with hepatitis A can make it tough to eat. It may be easier to snack during the day than to eat full meals. ✓ Avoid alcohol. It’s harder for your liver to handle medications and alcohol when you have the virus. Plus, drinking can lead to more liver damage. ▪ Hepatitis A Complications The virus usually doesn't cause any long-term problems or complications. Rarely, you may have liver failure or need a transplant. ▪ Hepatitis A Vaccine. The vaccine to prevent it is about 95% effective in healthy adults and can work for more than 20 years. In children, it’s about 85% effective and can last 15 to 20 years. ✓ Experts recommend that certain people get vaccinated: Travelers to countries with more hepatitis A infections Infants 6 to 11 months old who will be traveling internationally Children at 1 year old Families adopting children from countries where the virus is common Men who have sex with men People who have a blood clotting problem Those experiencing homelessness People who have direct contact with a person with the virus People who use recreational drugs People who have long-term liver disease Anyone else who wants to be protected against the virus  The hepatitis A vaccine includes two injections 6 months apart. A combination vaccine for hepatitis A and B has three shots over 6 months. ▪ Hepatitis A Vaccine and Travel. ✓ If you’re going to a country where hepatitis A is common and you’ve never had the virus or the vaccine, start the vaccination process as soon as you can. It takes 2 to 4 weeks after the first dose for the vaccine to work, but even one shot a few days before you leave will give you some protection. ✓ People who are allergic to something in the vaccine and children younger than 6 months might instead get a shot of immune globulin (IG), which will protect against hepatitis A for up to 2 months. ▪ Hepatitis A Prevention ✓ The vaccine is your best defense. If you come into contact with someone who has hepatitis A, you can get the vaccine or an IG shot within 2 weeks for some protection. ✓ Good hygiene is also important. Always wash your hands with soap and water after using the bathroom, before and after handling food, and after changing a diaper. ✓ When you travel to a place with poor sanitation, don’t drink tap water or eat raw food. Hepatitis A Transmission Prevention When you have hepatitis A, take these steps to keep from giving it to others: Avoid all sexual activity. Wash your hands after you use the bathroom or change diapers. Don’t prepare food for other people.  Growth hormone growth hormone: A protein made by the pituitary gland that helps control body growth and the use of glucose and fat in the body. Also called somatotropin. It stimulates the growth of essentially all tissues of the body, including bone. GH has direct metabolic effects on tissues by binding to cells, and has indirect effects by stimulating cells in the liver to produce insulin-like growth factors(IGFS or somatomedines).The main IGF is IGF-1 Direct effects: 1- Increased lipolysis – cells use fatty acid to generate ATP,sparing glucose 2- Glycogenolysis in the liver (breakdown of glycogen to glucose),which is a diabetogenic effect,due to the significant increase in blood glucose live 3- Stimulation of stem cell division and differentiation of daughter cell in epithelial and connective tissue. Indirect Effects : The effects of GH via IGF-1 can be thought of as “anabolic” (compound building) like insulin and include : Increase protein synthesis and cell growth Increase carbohydrate oxidation IGF-1 is important especially after a meal when glucose and amino acids are available in the blood. Glucose is taken up into cells through the action of insulin for ATP synthesis. At the same time, IGF-1 binds to plasma membrane receptors to increase their uptake of amino acids for protein synthesis, which uses up energy. Growth hormone function : - GH is anabolic hormone as it increase the transport of amino acids into muscles cells, help in protein, DNA, and RNA synthesis - GH increases lipolysis, ketogenesis, and fatty acid oxidation in liver -GH increases glucose production from liver and muscles -GH increases mineral absorption (calcium , magnesium, phosphate Stimulate mammary gland and milk production GH metabolic disorders: 1-Acromegaly Acromegaly is a rare condition where the body produces too much growth hormone, causing body tissues and bones to grow more quickly. Over time, this leads to abnormally large hands and feet. Symptoms abnormally large hands and feet large, prominent facial features (such as the nose and lips) and an enlarged tongue, skin changes such as thick, coarse skin. deepening of the voice, loss of sex drive abnormal periods (in women) and erection problems. Causes Pituitary tumors: Most acromegaly cases are caused by a noncancerous (benign) tumor (adenoma) of the pituitary gland. The tumor produces excessive amounts of growth hormone, causing many of the signs and symptoms of acromegaly. Nonpituitary tumors : tumors in other parts of the body, such as the lungs or pancreas, cause the disorder. In other cases, the tumors produce a hormone called growth hormone-releasing hormone (GH-RH), which signals the pituitary gland to make more GH. 2-Dwarfism (Growth hormone deficiency)  There is a deficiency of GH in infants leads to failure of growth. Symptom of dwarfism is abnormally and significantly shorter stature with respect to other persons in the same age, and especially in adults who have reached their final heights 3-Gigantism (Excessive increase of Growth Hormone during Childhood)is a disease resulting from excessive production of GH before the closure of epiphyseal plates, where there is accelerated growth of the long bones. screening tests 1-Insulin like growth factor (IGF) High levels of IGF-1 are responsible for most of the clinical manifestations of acromegaly. IGF-1 measured in the blood is the test of choice and will be raised in a patient with acromegaly. An elevated IGF-1 concentration in a patient showing signs of acromegaly confirms the diagnosis of acromegaly. Conversely, normal IGF-1 concentration suggests that acromegaly is unlikely. 2-Magnetic resonance imaging (MRI) to help pinpoint the location and size of a tumor on your pituitary gland. 3-Computed Tomography (CT) If MRI isn't available 4-Serum phosphate an increased serum phosphate level is common in acromegaly patients. 5-Blood test Definitive test for autonomous growth hormone production Glucose suppression test During this test, your GH blood level is measured both before and after you drink a preparation of sugar (glucose). In people who don't have acromegaly, the glucose drink typically causes the GH level to fall. But if you have acromegaly, your GH level will tend to stay high.  Jaundice Definition Yellow discoloration of the body tissue resulting from the accumulation of excess bilirubin. What is Bilirubin ? Old red blood cells are broken down in the spleen with haem as a breakdown product. This is converted (via a number of stages) to unconjugated bilirubin. Unconjugated bilirubin is then conjugated (made water soluble) by the liver. Normal total bilirubin level is less than 1 mg/dl Albumin capacity 20-25 mg/dl Types of jaundice Types Pre Hepatic (Hemolytic) Hepatic Post Hepatic (Cholestatic) Causes Hemolysis leading to Deficiency in: Deficiency of excretion excess production of –Uptake of conjugated bilirubin bilirubin. -conjugation by Udp due to obstruction of Due to: Hemolytic glucuronyl transferase biliary duct anemia -Excretion from Due to: stones or tumor hepatocytes Due to: infection or cirrhosis Type of Un conjugated Both Conjugated serum bilirubin affected Urine Absent Present Present bilirubin Other Signs of anemia High ALT & AST ALP>3 times features normal level What is neonatal Jaundice and it’s types? results from elevated total serum bilirubin (TSB) and clinically manifests as yellowish discoloration of the skin, sclera, and mucous membrane. In most cases, it is a mild, transient, and self-limiting condition and resolves without treatment referred to as "physiological jaundice. This is due to shorter life span of RBCs and excess bilirubin production along with compromised clearance of bilirubin due to impaired activity of uridine diphosphate glucuronosyltransferase (UGT), the enzyme needed for bilirubin conjugation. The UGT enzyme in a newborn has an activity of about 1% of the adult level. Pathalogical neonatal jaundice is when the bilirubin levels rise by more than 5 mg/dL/day or jaundice persists beyond 2 to 3 weeks in full-term infants. Treatment Phototherapy Enzyme inducer – phenobarbital Glucose administration to be converted to glucuronic acid. Obstructive jaundice Obstructive jaundice is a condition caused by a blockage in the bile ducts, preventing bile from flowing from the liver to the intestines. This results in the accumulation of conjugated bilirubin in the blood, leading to characteristic symptoms. Symptoms: 1-jaundice 2-pale colored stool 3-dark urine 4-itching 5-Right upper quadrant pain 6- weight loss and loss of appetite Causes: extra-hepatic cholestatic jaundice Gall stone in common bile duct. Carcinoma head of pancreas. intra-hepatic cholestatic jaundice Primary biliary cirrhosis. Some drugs such as phenothiazin Some forms of viral hepatitis. The clinical presentation Lab findings: Elevated total bilirubin with a predominantly high direct bilirubin suggests a post- hepatic cause. ALP is markedly elevated, which is a hallmark of bile duct obstruction or cholestasis. Normal or mildly elevated ALT indicates minimal hepatocellular injury. The urine is dark-colored (often described as tea-colored). This is due to the presence of water-soluble conjugated bilirubin, which is excreted in the urine when bile flow to the intestine is blocked(clay stool). Causes of itching? The itching (pruritus) is caused by the accumulation of bile salts and other pruritogenic substances (e.g., bilirubin) in the bloodstream and tissues due to impaired bile excretion.  Kidney failure Position of the kidneys: - Two kidneys are located against the posterior abdominal wall on either side of vertebral column. The left kidney is related interiorly to the stomach, pancreas, spleen and descending colon. The right one is related to the liver, second part of the duodenum and the ascending colon. The suprarenal (adrenal) glands cover the superior poles of kidneys. Functions of the kidneys: 1- Excretory function 2-Regulatory function 3-Endocrine function Causes of hypocalcemia Hypocalcemia occurs when Kidney can't activate vitamin D because there is no (1 alpha hydroxylase enzyme) to produce the active form of vitamin D ( 1,25 hydroxyl vitamin D3 )so causes vitamin D Deficiency which helps absorption of calcium properly. An increased level of phosphorus in your blood so decrease calcium level Kidney failure Kidney failure, also known as end-stage kidney disease, occurs when the kidneys are no longer able to adequately remove waste from your blood and control the level of fluid in your body. Kidney failure can happen suddenly or gradually. People with kidney failure need dialysis or a kidney transplant to stay alive. There are two different types of kidney failure Acute kidney failure has an abrupt onset and is potentially reversible Chronic kidney failure progresses slowly over at least three months and can lead to permanent kidney failure Acute Kidney Failure Reduced urine output Swollen legs, ankles, and feet Weakness and fatigue High blood pressure Confusion Chronic Kidney Failure Abnormal blood and urine tests Swelling in the face, hands, and feet Headaches High blood pressure Liver failure Liver Is the largest gland in the body, very vascular. Located in the upper right-hand portion of the abdominal cavity. Reddish brown in color. Weighs approx 3 pounds. The blood is supplied to the liver by the means of :- 1-The hepatic artery which supplies oxygenated blood 2-The hepatic portal vein which supplies nutrient-rich blood The Liver has many functions which includes :- Carbohydrates, Lipids and Proteins metabolism Detoxification (Ex.) Drugs Urea cycle Storage function as Glycogen, VitB12, Vit.D Formation of Bile Hematological functions RBCs production during fetal life Fibrinogen and prothrombin production (Clotting factors) Liver failure is a life-threatening condition that demands urgent medical care. Most often, Liver failure happens gradually, over many years. It’s the final stage of many liver diseases. But a rarer condition known as acute liver failure happens rapidly (in as little as 48 hours) and can be difficult to detect at first. Liver failure happens when large parts of the Liver become damaged beyond repair and the liver can’t work anymore.  - Causes of chronic liver failure cirrhosis Long -term alcohol consumption Malnutrition Hpatitis B, C Causes of acute liver failure Acetaminophen overdose Reactions to prescription or herbal medication Ingestion of poisonous wild mushroom Hepatitis A, B, C