Endocrine Exam PDF

Endocrine exam ============== Adrenal Glands - Medulla & Catecholamines ----------------------------------------- - **Catecholamines Produced**: - **Epinephrine (Adrenaline)**: About 80% of the catecholamines produced. - **Norepinephrine (Noradrenaline)**: About 20%. -...

Endocrine exam ============== Adrenal Glands - Medulla & Catecholamines ----------------------------------------- - **Catecholamines Produced**: - **Epinephrine (Adrenaline)**: About 80% of the catecholamines produced. - **Norepinephrine (Noradrenaline)**: About 20%. - **Dopamine**: A precursor to norepinephrine, but is produced in smaller amounts. **Functions of Catecholamines** 1. **Fight-or-Flight Response**: - **Epinephrine**: Increases heart rate, dilates airways, increases blood flow to muscles, and raises blood glucose levels. - **Norepinephrine**: Primarily increases vasoconstriction (narrowing of blood vessels), raising blood pressure. 2. **Metabolic Effects**: - Stimulates glycogen breakdown in the liver (glycogenolysis). - Increases lipolysis (fat breakdown). - Promotes increased glucose release for energy. 3. **Central Nervous System Effects**: - Increase alertness, arousal, and focus. - Enhances memory formation in response to stress. 4. **Cardiovascular Effects**: - **Epinephrine**: Increases heart rate and force of contraction. - **Norepinephrine**: Causes vasoconstriction, elevating blood pressure. **Stimuli for Release of Catecholamines** - **Stress** (physical or emotional, acute or chronic) - **Exercise**: Physical exertion triggers the release. - **Hypoglycemia**: Low blood glucose levels signal catecholamine release. - **Hypoxia**: Low oxygen levels in blood can stimulate release. - **Pain**: Acute pain or injury can stimulate release. - **Fear/Anxiety**: Psychological stress activates the sympathetic nervous system. **Inhibitors of Catecholamine Release** - **Parasympathetic Nervous System Activity**: The parasympathetic response counteracts the sympathetic (fight-or-flight) response, reducing catecholamine secretion. - **High Cortisol Levels**: Chronic high cortisol (due to long-term stress) may dampen acute catecholamine release. - **Negative Feedback**: High levels of catecholamines themselves can reduce further release through negative feedback mechanisms. - **Beta-Blockers**: Medications like beta-blockers can block the receptors for catecholamines, reducing their effects. **Adrenal Cortex** ------------------ - It produces steroid hormones, which are essential for regulating metabolism, immune function, and salt balance. - The adrenal cortex is divided into three distinct zones: 1. **Zona Glomerulosa** 2. **Zona Fasciculata** 3. **Zona Reticularis** **1. Zona Glomerulosa** - **Hormones Produced**: - **Aldosterone** (mineralocorticoid) - **Function**: - **Regulates sodium and potassium balance**. - **Increases sodium reabsorption** in kidneys, which leads to water retention and increased blood volume. - **Promotes potassium and hydrogen ion excretion** by the kidneys, helping maintain electrolyte balance and pH. - **Stimuli**: - **Renin-Angiotensin-Aldosterone System (RAAS)**: - Low blood pressure or low blood sodium levels stimulate the kidney to release **renin**. - Renin converts **angiotensinogen** to **angiotensin I**, which is converted to **angiotensin II** in the lungs. - Angiotensin II stimulates the **zona glomerulosa** to release aldosterone. - **High potassium levels** in the blood (hyperkalemia) stimulate aldosterone secretion. - **ACTH** (Adrenocorticotropic Hormone) from the pituitary gland has a minor role in stimulating aldosterone secretion. - **Inhibitors**: - **Low potassium levels** (hypokalemia) inhibit aldosterone release. - **Increased blood pressure** or adequate blood volume (via negative feedback from RAAS). **2. Zona Fasciculata** - **Hormones Produced**: - **Cortisol** (glucocorticoid) - **Function**: - **Regulates metabolism** (primarily carbohydrate, protein, and fat metabolism). - Stimulates **gluconeogenesis** (production of glucose from non-carbohydrate sources, e.g., proteins) in the liver. - **Increases blood glucose levels** by promoting the breakdown of proteins and fats. - **Anti-inflammatory**: Inhibits the immune response and reduces inflammation. - **Stress response**: Plays a role in the body's adaptation to stress (long-term). - **Stimuli**: - **ACTH (Adrenocorticotropic Hormone)**: Secreted by the anterior pituitary, stimulates cortisol release from the zona fasciculata. - **Stress** (physical, emotional, or metabolic stress) increases ACTH release from the pituitary, leading to increased cortisol release. - **Circadian rhythm**: Cortisol levels peak in the early morning and decrease at night. - **Inhibitors**: - **Negative feedback**: High cortisol levels in the blood inhibit ACTH release via feedback to the hypothalamus and pituitary. - **Increased blood glucose** can suppress cortisol secretion by negative feedback. **3. Zona Reticularis** - **Hormones Produced**: - **Androgens** (DHEA and androstenedione -- weak male sex hormones) - These hormones serve as precursors to **testosterone** and **estrogen**. - **Function**: - **Development of secondary sexual characteristics**: Though weak, the androgens from the zona reticularis contribute to sexual characteristics, particularly during puberty. - **Sexual differentiation**: Contributes to the onset of puberty, especially in females. - **Precursor to sex hormones**: In females, the adrenal androgens may be converted into estrogens. - **Stimuli**: - **ACTH**: Stimulates the zona reticularis to produce androgens. - **Stress**: Increased ACTH during stress can lead to the production of more androgens. - **Inhibitors**: - **Negative feedback** from high cortisol levels can reduce the secretion of ACTH, thus indirectly inhibiting androgen production. - **Estrogen/testosterone feedback**: In both men and women, feedback from sex hormones (estrogen and testosterone) can suppress ACTH release, decreasing androgen production. Insulin Overview ---------------- - **Produced by**: **Beta cells** of the **Islets of Langerhans** in the pancreas. - **Primary Role**: Regulates blood glucose levels by promoting the uptake and storage of glucose and other nutrients. **What Insulin Does (Functions)** 1. **Lowers Blood Glucose Levels**: - **Promotes glucose uptake** by cells (especially in muscle, fat, and liver). - **Stimulates glucose storage** in the form of **glycogen** in liver and muscle cells. - **Inhibits gluconeogenesis** (production of glucose from non-carbohydrate sources) in the liver. 2. **Promotes Fat Storage**: - **Stimulates lipogenesis** (fat synthesis) in adipose tissue. - **Inhibits lipolysis** (fat breakdown), promoting fat storage. 3. **Promotes Protein Synthesis**: - Stimulates **amino acid uptake** into cells. - **Enhances protein synthesis** in muscles, reducing protein breakdown. 4. **Regulates Metabolism**: - Facilitates nutrient storage (glucose, fats, proteins) during the **fed state**. - **Counteracts the effects of glucagon** and other hormones that increase blood glucose levels (e.g., cortisol, epinephrine). **Stimuli for Insulin Release** 1. **High Blood Glucose (Hyperglycemia)**: - The primary stimulus for insulin release. - After meals, glucose levels in the blood rise, triggering insulin secretion to promote glucose uptake and storage. 2. **Amino Acids**: - **Elevated amino acid levels** (especially after protein-rich meals) can stimulate insulin secretion. 3. **Incretin Hormones**: - **GLP-1 (Glucagon-like peptide-1)** and **GIP (Gastric inhibitory peptide)** are secreted by the gut in response to food intake, enhancing insulin release. 4. **Parasympathetic Nervous System**: - Activation of the parasympathetic system (rest and digest) increases insulin secretion during the feeding state. **Inhibitors of Insulin Release** 1. **Low Blood Glucose (Hypoglycemia)**: - Low blood sugar inhibits insulin release to prevent further lowering of glucose levels. 2. **Sympathetic Nervous System**: - Stress, exercise, and the "fight-or-flight" response stimulate the sympathetic nervous system, which **inhibits insulin release**. - This ensures that glucose remains available for energy during periods of stress. 3. **Somatostatin**: - Released by **delta cells** in the pancreas, somatostatin inhibits both insulin and glucagon secretion. 4. **High Cortisol Levels**: - Cortisol (from the adrenal cortex) can indirectly inhibit insulin release or reduce its effectiveness (insulin resistance). 5. **Fasting**: - During fasting states, insulin secretion is low to promote the use of stored energy. **Physiological Effects of Insulin** 1. **Glucose Regulation**: - **Decreases blood glucose levels** by promoting its uptake into muscle, fat, and liver cells for energy or storage as glycogen. 2. **Fat Metabolism**: - **Stimulates fat storage** in adipose tissue by facilitating glucose conversion to fat (lipogenesis). - **Inhibits fat breakdown** by preventing lipolysis. 3. **Protein Metabolism**: - **Increases protein synthesis** by promoting the uptake of amino acids into cells, particularly muscle cells. - **Reduces protein breakdown** (catabolism). 4. **Promotes Anabolic State**: - Overall, insulin is an **anabolic hormone**---it promotes the storage and building of energy reserves (glucose, fat, proteins). - This contrasts with **catabolic hormones** like glucagon, cortisol, and adrenaline, which stimulate the breakdown of energy stores. 5. **Inhibition of Gluconeogenesis**: - Reduces the liver\'s production of new glucose (gluconeogenesis), supporting the effect of lowering blood glucose. Glucagon Overview ----------------- - **Produced by**: **Alpha cells** of the **Islets of Langerhans** in the pancreas. - **Primary Role**: Raises blood glucose levels by promoting the release of glucose from storage sites in the body. **What Glucagon Does (Functions)** 1. **Increases Blood Glucose Levels**: - **Stimulates glycogenolysis**: Breaks down **glycogen** (the stored form of glucose) in the liver into **glucose** to raise blood sugar levels. - **Stimulates gluconeogenesis**: Promotes the production of **new glucose** from non-carbohydrate sources (e.g., amino acids) in the liver. 2. **Promotes Fat Breakdown (Lipolysis)**: - Stimulates the breakdown of stored **fat** in adipose tissue to release fatty acids and glycerol for energy. - Increases the release of **free fatty acids** into the bloodstream for use by tissues, particularly during fasting. 3. **Inhibits Glycogenesis**: - **Prevents glycogen synthesis**: Inhibits the process of **glycogenesis** (formation of glycogen) in the liver, ensuring glucose remains available in the bloodstream. 4. **Promotes Ketogenesis**: - **Increases ketone production** in the liver, providing an alternative energy source for the brain and muscles during prolonged fasting or low carbohydrate availability. **Stimuli for Glucagon Release** 1. **Low Blood Glucose (Hypoglycemia)**: - The **primary stimulus** for glucagon release. - When blood glucose levels are low (e.g., between meals or during fasting), glucagon is released to promote glucose release from the liver to raise blood glucose levels. 2. **High Amino Acid Levels**: - Elevated **amino acid levels** (especially after a high-protein meal) can stimulate glucagon release, helping convert amino acids into glucose (gluconeogenesis). 3. **Exercise**: - During physical activity, the body requires more energy, leading to the release of glucagon to increase glucose availability for muscle activity. 4. **Stress**: - Physical or emotional stress triggers the **sympathetic nervous system** and **stress hormones** (e.g., epinephrine), which increase glucagon release to provide more glucose for the body\'s fight-or-flight response. **Inhibitors of Glucagon Release** 1. **High Blood Glucose (Hyperglycemia)**: - Elevated blood glucose levels **inhibit** glucagon release. The body does not need additional glucose when blood sugar levels are already high. 2. **Insulin**: - **Insulin** (secreted by beta cells) **inhibits glucagon release**. After meals, insulin and glucagon work together in a counter-regulatory manner to balance blood glucose levels. 3. **Somatostatin**: - **Somatostatin** (secreted by delta cells of the pancreas) inhibits both **insulin** and **glucagon** release. This prevents excessive fluctuations in blood glucose levels. 4. **High Fatty Acid Levels**: - **Elevated fatty acids** in the bloodstream (from fat stores being used for energy) reduce glucagon release, as the body is obtaining sufficient energy from fats. **Physiological Effects of Glucagon** 1. **Increase in Blood Glucose (Hyperglycemia)**: - **Stimulates liver glycogen breakdown** (glycogenolysis) to release glucose into the bloodstream. - **Stimulates gluconeogenesis** to generate new glucose from amino acids and other substrates in the liver. 2. **Increased Ketone Production**: - During prolonged fasting or carbohydrate restriction, glucagon stimulates **ketogenesis** in the liver, producing ketones (alternative energy sources) from fatty acids for use by the brain and muscles. 3. **Increased Lipolysis**: - **Stimulates fat breakdown** (lipolysis) in adipose tissue, releasing fatty acids and glycerol into the bloodstream for energy use. 4. **Preserves Muscle Mass**: - By promoting **gluconeogenesis** from amino acids, glucagon helps preserve muscle protein stores during fasting periods. **Key Points to Remember** - **Glucagon** is a **counter-regulatory hormone** to insulin. It acts to **raise blood glucose levels** during fasting, stress, or exercise by stimulating glycogen breakdown, glucose production, and fat breakdown. - It is primarily triggered by **low blood glucose** (hypoglycemia) and also by **amino acids** after protein meals. - **Glucagon\'s actions** ensure that the body has adequate glucose (and other energy sources like fatty acids) for the brain and muscles, especially in times of fasting or physical exertion. - Its release is inhibited by **high blood glucose** and **insulin**. Diabetes Mellitus Overview -------------------------- - **Diabetes Mellitus** is a group of metabolic disorders characterized by **chronic hyperglycemia** (high blood glucose levels). - It results from either **insulin resistance**, **insulin deficiency**, or both. There are two main types of diabetes: 1. **Type 1 Diabetes** (T1D) 2. **Type 2 Diabetes** (T2D) **Normal Glucose Homeostasis** - **Insulin** (produced by **beta cells** of the pancreas) and **glucagon** (produced by **alpha cells** of the pancreas) regulate blood glucose. - After eating, blood glucose rises, stimulating insulin release to promote glucose uptake by cells for energy storage (glycogen, fat) and usage. - When blood glucose is low, glucagon is released to stimulate the liver to release glucose (via glycogen breakdown and gluconeogenesis). **Type 1 Diabetes (T1D)** - **Cause**: **Autoimmune destruction of beta cells** in the pancreas, leading to **insulin deficiency**. - **Insulin Production**: Very little or no insulin is produced by the pancreas. - **Onset**: Often occurs in **childhood** or **young adulthood** (but can develop at any age). **Physiological Effects in T1D:** 1. **Increased Blood Glucose (Hyperglycemia)**: - Without insulin, cells cannot take up glucose from the blood, leading to elevated blood glucose levels. 2. **Ketosis and Ketoacidosis**: - **Fat breakdown** increases (lipolysis) as the body cannot use glucose effectively. - Free fatty acids are converted into **ketones**, leading to **diabetic ketoacidosis (DKA)** if left untreated, which can be life-threatening. 3. **Increased Gluconeogenesis**: - The liver produces more glucose from non-carbohydrate sources (e.g., amino acids), further raising blood glucose levels. 4. **Polyuria, Polydipsia, Polyphagia**: - **Polyuria** (excessive urination) occurs due to high glucose levels in the urine, causing water loss. - **Polydipsia** (excessive thirst) results from dehydration due to fluid loss. - **Polyphagia** (excessive hunger) occurs because cells are unable to access glucose for energy, signaling hunger. **Type 2 Diabetes (T2D)** - **Cause**: Primarily **insulin resistance** in tissues (muscle, liver, fat), combined with a relative insulin deficiency. - **Insulin Production**: Initially, the pancreas compensates by producing more insulin, but over time, beta cells become fatigued and insulin secretion decreases. - **Onset**: Typically occurs in **adults** (but can occur in children), often associated with **obesity**, **physical inactivity**, and **genetics**. **Physiological Effects in T2D:** 1. **Insulin Resistance**: - **Tissues (muscle, fat, liver)** become resistant to insulin, requiring higher levels of insulin for the same effect. 2. **Hyperinsulinemia**: - Initially, the pancreas secretes more insulin to overcome insulin resistance, leading to **high insulin levels** in the blood. 3. **Impaired Glucose Uptake**: - Because cells do not respond properly to insulin, glucose remains elevated in the bloodstream. 4. **Increased Hepatic Glucose Production**: - The liver continues to produce glucose (via gluconeogenesis), contributing to hyperglycemia. 5. **Beta Cell Dysfunction**: - Over time, pancreatic beta cells become **exhausted** and fail to produce enough insulin, worsening the condition. 6. **Symptoms**: Similar to T1D but often **gradual onset**: - **Polyuria**, **polydipsia**, and **polyphagia**. - Fatigue, blurred vision, slow wound healing, and recurrent infections are common. **Common Physiological Features of Both T1D and T2D** - **Hyperglycemia**: Elevated blood glucose due to insufficient insulin action. - **Increased Blood Lipids**: Both types often result in abnormal lipid profiles (e.g., high triglycerides, low HDL). - **Impaired Protein Metabolism**: Both types can lead to muscle wasting (catabolism) due to the inability to use glucose properly. **Chronic Complications of Diabetes Mellitus** - **Macrovascular Complications** (Large blood vessels): - **Atherosclerosis** (plaque buildup in arteries), leading to: - **Coronary artery disease** (increased risk of heart attacks) - **Peripheral arterial disease** (reduced blood flow to extremities) - **Stroke** (increased risk of cerebrovascular events) - **Microvascular Complications** (Small blood vessels): - **Retinopathy**: Damage to the small blood vessels in the eyes, leading to blindness. - **Nephropathy**: Kidney damage, which may lead to kidney failure (end-stage renal disease). - **Neuropathy**: Nerve damage, particularly in the legs and feet (peripheral neuropathy), leading to pain, numbness, and increased risk of infections. - **Increased Risk of Infection**: Elevated blood glucose impairs immune function, increasing susceptibility to infections. **Diagnosis of Diabetes Mellitus** 1. **Fasting Blood Glucose** ≥ 126 mg/dL (7.0 mmol/L) 2. **Oral Glucose Tolerance Test (OGTT)**: 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) 3. **HbA1c** (Glycated Hemoglobin): ≥ 6.5% (reflects average blood glucose over 2-3 months) **Management of Diabetes Mellitus** - **Type 1 Diabetes**: - Requires **insulin therapy** (multiple injections or insulin pumps). - **Blood glucose monitoring** is essential. - **Type 2 Diabetes**: - **Lifestyle modifications** (diet, exercise) are key in managing insulin resistance. - Medications (e.g., **metformin**, **sulfonylureas**, **GLP-1 agonists**, **SGLT2 inhibitors**) may be used to improve insulin sensitivity and lower blood glucose. - **Insulin therapy** may eventually be required as the disease progresses. Testes Overview --------------- - **Location**: The testes are the male gonads, located in the **scrotum**. - **Primary Functions**: - **Spermatogenesis**: Production of sperm. - **Hormone Production**: Mainly **testosterone**. **Testes Cell Types** 1. **Sertoli Cells (Nurse Cells)**: - **Location**: Found within the **seminiferous tubules** of the testes. - **Function**: - **Support spermatogenesis**: Nourish and protect developing sperm. - **Form the blood-testis barrier**: Protects developing sperm from autoimmune attack. - **Secretion of Inhibin**: Inhibits FSH (Follicle-Stimulating Hormone) release to regulate spermatogenesis. - **Secretion of Androgen-Binding Protein (ABP)**: Binds to testosterone to keep it concentrated in the seminiferous tubules for spermatogenesis. - **Phagocytosis**: Engulf and digest defective sperm cells. - **Support the process of meiosis and spermiogenesis**. 2. **Leydig Cells (Interstitial Cells)**: - **Location**: Found in the **interstitial tissue** between the seminiferous tubules. - **Function**: - **Secretion of Testosterone**: The primary hormone responsible for male sexual development, spermatogenesis, and maintenance of secondary sexual characteristics. - **Stimulated by LH (Luteinizing Hormone)** from the pituitary gland. 3. **Germ Cells (Sperm Cells)**: - **Location**: Found within the seminiferous tubules, these are the developing sperm cells. - **Types of Germ Cells**: - **Spermatogonia**: The stem cells that undergo mitosis to produce spermatocytes. - **Primary Spermatocytes**: Undergo meiosis to form haploid secondary spermatocytes. - **Secondary Spermatocytes**: Divide further to form spermatids. - **Spermatids**: Undifferentiated sperm cells that mature into spermatozoa (sperm). **Testes Hormones** 1. **Testosterone** (Main Male Sex Hormone) - **Produced by**: **Leydig cells** in response to **LH** (Luteinizing Hormone). - **Functions**: - **Development of male secondary sexual characteristics** (e.g., deepening voice, facial hair, muscle growth). - **Stimulates spermatogenesis** in the seminiferous tubules. - **Maintains libido** and erectile function. - **Regulates male pattern of fat distribution**. - **Supports bone density** and muscle mass. - **Negative feedback**: High testosterone levels inhibit the release of both **LH** and **GnRH** (Gonadotropin-Releasing Hormone) to regulate production. 2. **Inhibin** - **Produced by**: **Sertoli cells**. - **Function**: - **Inhibits FSH (Follicle-Stimulating Hormone)** release from the anterior pituitary. - **Regulates spermatogenesis**: When sperm production is sufficient, inhibin is released to reduce FSH and slow sperm production. 3. **Follicle-Stimulating Hormone (FSH)** (Indirect Role in Hormonal Regulation) - **Produced by**: The **anterior pituitary gland**. - **Function**: - Stimulates **Sertoli cells** to support spermatogenesis. - Acts indirectly to enhance **testosterone production** by stimulating **Leydig cells**. 4. **Luteinizing Hormone (LH)** - **Produced by**: The **anterior pituitary gland**. - **Function**: - Stimulates **Leydig cells** to produce **testosterone**. - Plays a key role in the regulation of **testosterone levels** for male reproductive function. 5. **Gonadotropin-Releasing Hormone (GnRH)** - **Produced by**: The **hypothalamus**. - **Function**: - Stimulates the **anterior pituitary** to release **FSH** and **LH**, which in turn regulate spermatogenesis and testosterone production. **Hormonal Regulation of Testes Function** - **GnRH** from the hypothalamus stimulates the **anterior pituitary** to release **FSH** and **LH**. - **FSH** acts on **Sertoli cells** to support spermatogenesis. - **LH** acts on **Leydig cells** to stimulate testosterone production. - **Testosterone** has **negative feedback** on both the hypothalamus and anterior pituitary to **suppress GnRH** and **LH** release when levels are high. - **Inhibin** released from **Sertoli cells** exerts feedback inhibition specifically on **FSH** to modulate spermatogenesis. Ovaries Overview ---------------- - **Location**: Paired organs located on either side of the uterus in females. - **Primary Functions**: - **Oogenesis**: Production of oocytes (eggs). - **Hormone Production**: Estrogen, progesterone, inhibin, and small amounts of androgens. - **Ovulation**: Release of a mature oocyte from the follicle. **Ovarian Follicles** - **Ovarian Follicle**: A structure that contains a developing oocyte (egg) surrounded by layers of cells. The follicle grows and matures in several stages until ovulation. - **Follicular Development**: Oocytes develop in the follicles in response to hormonal signals, starting from primordial follicles to primary, secondary, and tertiary (Graafian) follicles. - **Follicular Cells**: The two main types of cells involved in the development of the follicle are **granulosa cells** and **thecal cells**. **Granulosa Cells** - **Location**: Found in layers surrounding the oocyte within the ovarian follicle. - **Function**: - **Support oocyte development**: Provide physical and nutritional support to the developing oocyte. - **Convert androgens to estrogens**: Granulosa cells contain the enzyme **aromatase**, which converts **androgens** (produced by the thecal cells) into **estrogens**. - **Secretion of Inhibin**: Inhibits **FSH** (Follicle-Stimulating Hormone) production from the anterior pituitary to regulate follicular development. - **Production of Estrogen**: Granulosa cells produce estrogen as the follicle matures. **Thecal Cells** - **Location**: Found in the outer layer of the ovarian follicle, surrounding the granulosa cells. - **Function**: - **Production of Androgens**: Thecal cells produce **androgens** (such as **androstenedione**), which are precursors to estrogen. - **Secretion of Progestins**: Thecal cells also produce small amounts of progesterone during the luteal phase (after ovulation). - **Support for estrogen production**: The androgens produced by thecal cells are converted to estrogen by granulosa cells under the influence of **FSH**. **Hormones Involved in Ovarian Follicle Function** 1. **Estrogen**: - **Produced by**: **Granulosa cells** (from the conversion of androgens produced by the thecal cells). - **Functions**: - **Stimulates the growth and maturation of the ovarian follicle**. - **Regulates the menstrual cycle**, promoting the proliferation of the endometrial lining in the uterus. - **Development of secondary sexual characteristics** (breast development, widening of hips, etc.). - **Positive feedback** on **LH** (Luteinizing Hormone) near the end of the follicular phase, leading to the **LH surge** and ovulation. 2. **Progesterone**: - **Produced by**: **Granulosa lutein cells** in the **corpus luteum** (post-ovulation). - **Functions**: - Prepares the **endometrium** for implantation of a fertilized egg. - **Inhibits further ovulation** during the luteal phase (via negative feedback on **FSH** and **LH**). 3. **Inhibin**: - **Produced by**: **Granulosa cells**. - **Function**: - Inhibits **FSH** release from the anterior pituitary. - Regulates the development of follicles during the menstrual cycle, particularly by reducing FSH levels as a single follicle becomes dominant. 4. **Androgens (e.g., Androstenedione)**: - **Produced by**: **Thecal cells**. - **Function**: - Precursors to **estrogen** synthesis in granulosa cells. - Small amounts of androgens are produced, which are then converted to estrogens by granulosa cells in the presence of FSH. 5. **Luteinizing Hormone (LH)**: - **Produced by**: **Anterior pituitary gland**. - **Function**: - Stimulates the **thecal cells** to produce androgens. - Involved in the **LH surge** that triggers **ovulation** (release of the egg from the mature follicle). - After ovulation, LH helps the **granulosa** and **thecal cells** transform into **luteal cells** in the corpus luteum, which produces progesterone. 6. **Follicle-Stimulating Hormone (FSH)**: - **Produced by**: **Anterior pituitary gland**. - **Function**: - Stimulates **granulosa cells** to proliferate and secrete estrogen. - Facilitates the conversion of **androgens** to **estrogens** by granulosa cells. - Helps in the selection of a dominant follicle in the ovary. 7. **Gonadotropin-Releasing Hormone (GnRH)**: - **Produced by**: **Hypothalamus**. - **Function**: - Stimulates the **anterior pituitary** to release **FSH** and **LH**. - **Pulsatile release** of GnRH is essential for normal function of the menstrual cycle and ovarian follicle development. **Follicular Development and Hormonal Regulation** 1. **Follicular Phase**: - **FSH** stimulates the growth of multiple ovarian follicles. - **Granulosa cells** increase estrogen production. - As the follicles grow, they secrete increasing amounts of estrogen. - Rising estrogen levels promote a **positive feedback loop** on the anterior pituitary, leading to a surge in **LH**. 2. **Ovulation**: - The **LH surge** triggers the final maturation and release of the egg (ovulation) from the dominant follicle. 3. **Luteal Phase**: - After ovulation, the ruptured follicle becomes the **corpus luteum**. - **Corpus luteum** produces **progesterone** and some estrogen to prepare the endometrium for implantation. - **Inhibin** also decreases FSH secretion to prevent the growth of additional follicles during the luteal phase. 4. **If No Pregnancy**: - The corpus luteum degenerates, progesterone levels drop, and the endometrial lining is shed (menstruation). - **FSH** levels rise again to stimulate the next menstrual cycle. Calcium Homeostasis Overview ---------------------------- - **Purpose**: Maintain stable blood calcium levels to ensure proper function of muscles, nerves, bones, and other tissues. - **Normal Blood Calcium Range**: 8.5--10.5 mg/dL (2.12--2.62 mmol/L). - **Organs Involved**: - **Bones**: Major storage site for calcium. - **Kidneys**: Filter and regulate calcium excretion. - **Intestines**: Absorb calcium from diet. - **Parathyroid Glands**: Release hormones to regulate calcium levels. **Key Regulators of Calcium Homeostasis** 1. **Parathyroid Hormone (PTH)**: - **Produced by**: **Parathyroid glands** (4 small glands located on the back of the thyroid). - **Function**: - **Increases blood calcium levels** when they are too low. - Stimulates **osteoclast activity** in bones to release calcium into the bloodstream. - Enhances calcium reabsorption in the **kidneys**. - Stimulates **activation of vitamin D** (calcitriol) in the kidneys, which increases calcium absorption from the intestines. 2. **Calcitonin**: - **Produced by**: **Thyroid gland**, specifically the **C cells**. - **Function**: - **Decreases blood calcium levels** when they are too high. - Inhibits **osteoclast activity** in bones, reducing calcium release from bones into the blood. - Increases calcium excretion by the **kidneys**. 3. **Vitamin D (Calcitriol)**: - **Produced by**: **Skin**, **liver**, and **kidneys**. - **Function**: - In its active form (**calcitriol**), it enhances **calcium absorption** from the **small intestine**. - Helps in the **mobilization of calcium** from bones (though to a lesser degree than PTH). - Works synergistically with PTH to maintain calcium levels. **Mechanisms of Calcium Regulation** 1. **Bone Regulation (Osteoblasts and Osteoclasts)**: - **Osteoclasts**: Break down bone tissue to release calcium into the bloodstream. Activated by **PTH**. - **Osteoblasts**: Build bone and deposit calcium in bone matrix. Inhibited by **PTH** but stimulated by **calcitonin**. 2. **Kidneys**: - **PTH** increases calcium reabsorption in the **proximal convoluted tubule** and **loop of Henle**. - **Calcitonin** increases calcium excretion by the kidneys. - **Vitamin D** (calcitriol) promotes calcium reabsorption in the kidneys. - **Renal Tubules**: Control the final calcium concentration in urine, which helps fine-tune calcium balance. 3. **Intestines**: - **Vitamin D** increases calcium absorption from the diet in the **small intestine**. - Calcium absorption is enhanced in the presence of **active vitamin D** and **PTH**. **Feedback Mechanisms for Calcium Regulation** 1. **Low Blood Calcium (Hypocalcemia)**: - **Stimulus**: Calcium levels fall below the normal range. - **Response**: - **PTH** is released from the parathyroid glands. - **PTH** stimulates osteoclasts to release calcium from bones. - **PTH** enhances calcium reabsorption by the kidneys and promotes activation of vitamin D. - **Vitamin D** increases calcium absorption from the intestines. - Result: Blood calcium levels rise to normal range. 2. **High Blood Calcium (Hypercalcemia)**: - **Stimulus**: Calcium levels rise above the normal range. - **Response**: - **Calcitonin** is released from the thyroid. - **Calcitonin** inhibits osteoclast activity, decreasing calcium release from bones. - **Calcitonin** increases calcium excretion through the kidneys. - Result: Blood calcium levels fall to normal range. **Effects of Calcium Imbalance** 1. **Hypocalcemia (Low Calcium Levels)**: - Can lead to **tetany** (muscle spasms), **numbness** or **tingling** in the fingers and toes, and **seizures**. - May occur due to **hypoparathyroidism** (low PTH), **vitamin D deficiency**, or **renal failure**. 2. **Hypercalcemia (High Calcium Levels)**: - Can cause **kidney stones**, **bone pain**, **constipation**, **fatigue**, and **confusion**. - May result from **hyperparathyroidism** (excessive PTH), **malignancy** (tumors releasing PTHrP), or **excessive vitamin D**. Adrenal Androgens Overview -------------------------- - **Adrenal Androgens**: A group of **steroid hormones** produced by the **adrenal glands**, specifically by the **adrenal cortex**. - **Location**: Secreted by the **zona reticularis** of the adrenal cortex (the innermost layer). - **Types of Androgens**: - **Dehydroepiandrosterone (DHEA)** - **DHEA sulfate (DHEAS)** - **Androstenedione** - **Primary Function**: Precursor hormones that are converted into **testosterone** and **estrogen** in peripheral tissues. **Production and Regulation of Adrenal Androgens** 1. **Stimuli for Secretion**: - **ACTH (Adrenocorticotropic Hormone)** from the anterior pituitary stimulates the adrenal cortex. - **CRH (Corticotropin-Releasing Hormone)** from the hypothalamus promotes ACTH secretion, which in turn stimulates androgen production in the adrenal glands. - **Stress** and **circadian rhythms** can also influence the secretion of ACTH and therefore adrenal androgens. 2. **Regulation**: - **Negative feedback**: High levels of androgens (or downstream estrogens/testosterone) can inhibit ACTH and CRH secretion. - **Aging**: Levels of adrenal androgens (especially DHEA and DHEAS) decline with age. **Key Adrenal Androgens** 1. **Dehydroepiandrosterone (DHEA)**: - **Most abundant** adrenal androgen. - **Produced by**: Zona reticularis of the adrenal cortex. - **Function**: - **Precursor to sex hormones**: Converted to testosterone and estrogen in peripheral tissues (e.g., skin, liver). - Plays a role in **pubertal development**, but less potent than gonadal androgens like testosterone. - **Influences mood** and **energy levels**. 2. **DHEA Sulfate (DHEAS)**: - **Sulfated form of DHEA**, more stable and abundant in circulation than DHEA. - **Converted to DHEA** in peripheral tissues, where it is further converted into **testosterone** or **estrogen**. - Levels peak in the **early 20s** and decline with age. - Used as a **biomarker for adrenal function** and aging. 3. **Androstenedione**: - **Precursor to testosterone** and **estrogen**. - **Produced by**: Zona reticularis of the adrenal cortex and gonads. - **Converted to testosterone** in men and estrogen in women in peripheral tissues (mainly adipose tissue). - Plays a role in **sexual development** and **libido** in both men and women. **Physiological Effects of Adrenal Androgens** 1. **Development of Male Characteristics**: - Androgens from the adrenal glands contribute to **pubertal development** (e.g., increased body hair, deepening voice) in both men and women, though less potent than gonadal testosterone. - **Sexual dimorphism**: Responsible for some secondary sexual characteristics like axillary and pubic hair in both sexes. 2. **Influence on Female Sexual Health**: - **Libido**: Androgens influence sexual desire in both women and men. - **Hormonal Balance**: In women, adrenal androgens are a primary source of testosterone, especially after menopause when ovarian testosterone production decreases. 3. **Metabolic Effects**: - **Fat distribution**: Adrenal androgens can influence fat deposition, contributing to **android-type fat distribution** (i.e., abdominal fat). - **Muscle mass**: In both genders, androgens support the maintenance of lean muscle mass. 4. **Mood and Energy**: - **DHEA** is thought to have **mood-enhancing** effects and may have a role in combating **fatigue**. - Low levels of DHEA have been associated with **depression** and **chronic fatigue syndrome**. 5. **Immune Function**: - **DHEA** has **immunomodulatory** effects, helping to regulate immune responses and inflammation. Puberty Overview ---------------- - **Definition**: Puberty is the period of physical and hormonal changes that lead to sexual maturity and the ability to reproduce. - **Age Range**: Typically occurs between ages **8-14** in girls and **9-15** in boys. - **Key Hormonal Changes**: - **Hypothalamus** releases **GnRH (gonadotropin-releasing hormone)**. - **GnRH** stimulates the **anterior pituitary** to release **FSH (follicle-stimulating hormone)** and **LH (luteinizing hormone)**. - **FSH and LH** stimulate the **gonads** (ovaries in girls, testes in boys) to produce **sex hormones** (estrogen and progesterone in girls, testosterone in boys). Menstrual Cycle Overview ------------------------ - **Definition**: A regular cycle of physiological changes in women's bodies that prepares for pregnancy. It typically lasts **28 days** but can range from **21 to 35 days**. - **Key Phases**: **Menstrual phase**, **Follicular phase**, **Ovulation**, and **Luteal phase**. - **Regulated by**: **GnRH**, **FSH**, **LH**, **estrogen**, and **progesterone**. **Menstrual Cycle Phases (In Point Form)** **1. Menstrual Phase (Day 1-5):** - **First day of menstruation** is considered Day 1 of the cycle. - **Low levels of estrogen and progesterone** lead to the **shedding of the uterine lining** (endometrium). - **Bleeding** occurs due to the breakdown of the endometrial tissue. **2. Follicular Phase (Day 1-13):** - **FSH** stimulates the growth of **follicles** in the ovaries. - **Estrogen** is produced by developing follicles, promoting the growth and maturation of the uterine lining (endometrium). - **One dominant follicle** matures and prepares to release an egg (ovum) during ovulation. **3. Ovulation (Day 14):** - **LH surge** triggered by rising **estrogen** levels causes the **dominant follicle** to release an egg. - The egg is released from the **ovary** and travels into the **fallopian tube**. - **Cervical mucus** becomes **thin and slippery**, facilitating sperm movement. **4. Luteal Phase (Day 15-28):** - After ovulation, the **ruptured follicle** becomes the **corpus luteum**, which produces **progesterone**. - **Progesterone** prepares the endometrium for possible implantation of a fertilized egg. - If **pregnancy does not occur**, the **corpus luteum degenerates**, causing **progesterone** and **estrogen** levels to fall. - **Menstruation** begins if implantation does not happen, and the cycle restarts. **Hormonal Regulation of the Menstrual Cycle** - **GnRH (Gonadotropin-Releasing Hormone)**: Released by the hypothalamus, stimulates the pituitary gland to secrete **FSH** and **LH**. - **FSH (Follicle-Stimulating Hormone)**: Stimulates **follicular development** and **estrogen** production in ovaries. - **LH (Luteinizing Hormone)**: Triggers **ovulation** and supports the formation of the **corpus luteum**. - **Estrogen**: Builds the **endometrial lining** during the follicular phase and increases during ovulation to trigger the LH surge. - **Progesterone**: Produced by the **corpus luteum**, stabilizes the endometrial lining for pregnancy, and inhibits further ovulation during the luteal phase. Summary of Hormonal Changes in Pregnancy ---------------------------------------- - **hCG** maintains the pregnancy and prevents menstruation. - **Progesterone** ensures uterine relaxation and maintains the pregnancy. - **Estrogen** supports uterine and mammary gland growth. - **Relaxin** prepares the body for childbirth. - **Prolactin** prepares the breasts for lactation. - **hPL** modifies metabolism and supports fetal growth. - **Oxytocin** triggers labor and milk ejection. - **Cortisol** helps with fetal development and metabolism. - **Thyroid hormones** regulate metabolism and fetal brain development. - **hGH** supports growth and protein synthesis. General Adaptation Syndrome (GAS) Overview ------------------------------------------ - **Definition**: The **General Adaptation Syndrome** is the body's **adaptive response** to stress, including the physical stress of exercise. - **Phases**: The GAS consists of three distinct stages: 1. **Alarm Stage** 2. **Resistance Stage** 3. **Exhaustion Stage** - The GAS model was first proposed by **Hans Selye** in the 1930s to describe how the body reacts to stressors over time. **1. Alarm Stage (Initial Response)** - **Trigger**: This phase begins when the body is exposed to an **acute exercise stressor** (e.g., intense workout, heavy lifting). - **Physiological Response**: - **Immediate activation of the sympathetic nervous system** (\"fight or flight\" response). - **Increased heart rate, blood pressure, and breathing rate**. - **Release of stress hormones** like **cortisol** and **epinephrine**. - **Muscle fatigue** and **energy depletion**. - **Decreased immune function** immediately after intense exercise. - **Duration**: Short-term response, lasting from **minutes to hours**. - **Purpose**: The body mobilizes energy stores and prepares for the stressor. In this phase, the body is not yet adapted to the stressor and experiences **disruption** in homeostasis. **2. Resistance Stage (Adaptation Phase)** - **Trigger**: This phase begins after the body has successfully dealt with the stressor from the alarm stage. - **Physiological Response**: - **Adaptation to the exercise**: The body starts to adjust and adapt to the stressor. - **Increased energy efficiency**: The muscles and systems involved in the exercise become more efficient. - **Hypertrophy (muscle growth)**: Muscle fibers grow stronger in response to strength training (protein synthesis increases). - **Enhanced cardiovascular and respiratory efficiency**: Heart rate and stroke volume increase during exercise to improve oxygen delivery. - **Increased mitochondrial density** in muscles for better energy production. - **Improved endurance**: The body becomes more efficient at metabolizing fat and carbohydrates for sustained energy during prolonged activities. - **Recovery**: This phase involves **tissue repair**, **glycogen replenishment**, and restoration of homeostasis. - **Duration**: This stage can last for **weeks to months** depending on the intensity and consistency of training. - **Purpose**: The body is now better able to tolerate the exercise load and recovers faster. It adapts by improving strength, endurance, and overall fitness. **3. Exhaustion Stage (Overtraining or Burnout)** - **Trigger**: If the stressor is **too intense, too frequent**, or **insufficient recovery** occurs between exercise sessions. - **Physiological Response**: - **Overtraining**: The body's ability to recover and adapt to stressors becomes overwhelmed. - **Decreased performance**: Strength, endurance, and overall fitness levels may plateau or decrease. - **Increased risk of injury**: Muscles, joints, and connective tissues become more susceptible to strains and tears. - **Chronic fatigue** and **decline in immune function**. - **Elevated levels of stress hormones** like **cortisol** (catabolic effects). - **Mood disturbances** such as irritability, anxiety, or depression. - **Decreased motivation** and **poor sleep quality**. - **Duration**: This stage can last for **weeks to months**, and if prolonged without proper intervention, can lead to **burnout** or **overtraining syndrome**. - **Purpose**: If stress exceeds the body\'s ability to adapt, it leads to **fatigue**, **depletion of energy stores**, and a **decline in physical performance**.