advphysII-examI.docx

**[Endocrine Function]** 1. **Introduction to Endocrine Glands** - Found throughout the body and within upper and GI tract - Chemical messengers released from glands are hormones i. Autocrine -- within the cells ii. Paracrine -- between the cells iii. Endo...

**[Endocrine Function]** 1. **Introduction to Endocrine Glands** - Found throughout the body and within upper and GI tract - Chemical messengers released from glands are hormones i. Autocrine -- within the cells ii. Paracrine -- between the cells iii. Endocrine -- between remote cells - **Functions:** iv. Differentiation of reproductive and central nervous system in developing fetus v. Stimulation of sequential growth and development during childhood and adolescence vi. Coordination of the male and female reproductive systems vii. Maintenance of an optimal internal environment throughout the lifespan viii. Initiation of corrective and adaptive responses when emergency demands occurs 2. **Describe the chemical factors, endocrine factors, and neural factors that stimulate hormone release, and provide an** **example of each.** - **Regulation of Hormone Release:** ix. When to start secretion is dictated by: circadian/diurnal rhythms, pulsatile/cyclic rhythms, and patterns that depend on substrate levels (electrolyte levels or hormone levels) x. Operate within (negative or positive) feedback loop systems to maintain optimal internal environment xi. Only affects cells with appropriate receptors xii. Steroid hormones are excreted by kidneys or metabolized by the liver -- peptide hormones are catabolized by circulating enzymes - **Chemical Factors** (blood levels of a specific chemical) xiii. Serum glucose increases, causing secretion of insulin - **Endocrine Factors** (a hormone from one endocrine gland controls another endocrine gland) xiv. Adrenal cortex releases cortisol, which regulates/stimulates insulin release from beta cells in the pancreas - **Neural control** (neurons directly control the endocrine gland) xv. Autonomic nervous system directly stimulates the insulin-secreting cells of the pancreas 3. **Compare negative feedback and positive feedback, and give an example of each.** - **Negative Feedback** xvi. Most common xvii. Occurs when something reduces the synthesis and secretion of a hormone xviii. Example: Body temperature regulation -- when your body temperature gets too high, you sweat which cools you down - **Positive Feedback** xix. Less common xx. Occurs when a stimulus increases the synthesis and secretion of a hormone xxi. Can also occur when the hormone itself causes a further increases in synthesis/secretion xxii. Example: Blood clotting -- when a wound occurs, platelets aggregate at the site and release chemicals that attract even more platelets, rapidly forming a clot to stop bleeding; this process accelerates itself until the clot is large enough to seal the wound 4. **Hormone Transport: Water Soluble vs Lipid Soluble Hormones** - **Only unbound (free) hormones can initiate changes within a target cell** - **[Water-soluble hormones]** xxiii. Freely circulate in unbound form xxiv. Generally have a very short ½ life due to circulating enzymes - **[Lipid-Soluble hormones]** xxv. Transported bound to a carrier protein and can remain in blood for hours to days 5. **Compare/contrast up-regulation and down-regulation in terms of hormonal sensitivity, and provide an example of each.** - Hormone Receptors -- recognize and bind with high affinity to their hormones, initiate a signal to appropriate intracellular effectors - **Hormonal sensitivity/affinity is directly related to the concentration of how many receptors are on the cell:** xxvi. Up-regulation: low concentrations of hormone, increases the number of receptors per cell xxvii. Down-regulation: high concentrations of hormone decreases the number or affinity of receptors 6. **Differentiate between first messengers and second messengers, and give examples of each.** - **Water Soluble Hormones** -- cannot cross lipid bilayer xxviii. 1^st^ messenger: hormone xxix. 2^nd^ messenger: chemical *(Second messengers are tissue-specific, what cAMP does in one tissue may be different in another tissue)* 1. cAMP 2. cGMP 3. Calcium 4. IP3 5. Membrane-associated diacylglycerol 6. Tyrosine kinase system - **Steroid (Lipid-Soluble Receptors)**  - Synthesized from cholesterol (except for thyroid hormones) - Can cross plasma and nuclear membranes by simple diffusion - Glucocorticoids - Androgens - Estrogens - Progestins - Mineralocorticoids - Vitamin D - Retinoid - **Binding of hormone with receptor causes:** - Acting on pre-existing channel-forming proteins to alter membrane permeability - Activating pre-existing proteins through a second messenger system - Activating genes to cause protein synthesis - **Direct hormone effects** - Obvious changes in cell function that specifically result from stimulation by a particular hormone - Ex: insulin has a direct effect on skeletal muscle cells, causing increased glucose transport into these cells - **Permissive Effects** - Less obvious hormone-induced changes that facilitate maximal response or function of a cell - Ex: insulin has a permissive effect on mammary cells, facilitating their response to prolactin 7. **Identify the hormones secreted by each of the following glands and their target tissue:** - **[Hypothalamic-Pituitary Axis ]** xxx. **Hypothalamic-Pituitary Axis** 7. Integrates the neurologic and endocrine system \~negative feedback must kick in at both locations\~ - **[Hypothalamus]** xxxi. Located at the base of the brain xxxii. Connected to pituitary gland xxxiii. Secretes several hormones that cause secretion or inhibition of hormones in the pituitary gland xxxiv. Also **synthesizes oxytocin and ADH, which are then stored in the pituitary gland**  - **[Anterior pituitary]** 8. **Adenohypophysis (anterior)** a. Most of the weight (75%) b. Most of the hormones (3 groups) i. Corticotropin-related (ACTH) 1. ACTH is a hormone your pituitary gland releases that plays a role in how your body responds to stress 2. ACTH triggers adrenal glands to produce cortisol (stress hormone) and androgens ii. Glycoproteins iii. Somatotropins c. Responsive to hypothalamus d. FLAT PiG (FSH, LH, ACTH, TSH, Prolactin, GH) - **[Posterior pituitary]** 9. **Neurohypophysis (posterior)** e. **Oxytocin** - stored here iv. Secretion d/t: 3. Suckling 4. Mechanical distension of female reproductive trial (child birth) v. Binds to receptors in mammary tissues, causing contraction, milk expression in lactating women vi. Also stimulates uterine contractions (decreases bleeding loss) vii. **Has an anti-diuretic effect in both sexes can cause water toxicity** f. **Anti-diuretic hormone** -- stored here viii. Secretion d/t: 5. Increased osmolality (detected by osmoreceptors of hypothalamus) 6. Reduced intravascular volume (detected by baroreceptors in LA, carotid arteries, aortic arch) ix. Binds to V2 receptors in renal tubular cells, increasing their permeability to water (water reabsorption) g. Responsive to cholinergic and adrenergic neurotransmitters (glutamate and GABA) - **[Thyroid]** xxxv. 1 thyroid gland xxxvi. **Regulation of thyroid hormone secretion** 10. Negative feedback loop involving hypothalamus, anterior pituitary, and thyroid gland xxxvii. **Thyroid stimulating hormone causes:** 11. Immediate release of thyroid hormones 12. Increase in iodide uptake and oxidation 13. Increase in thyroid hormone synthesis 14. Increase in synthesis and secretion of prostaglandins xxxviii. **Thyroid hormone structure** 15. T3-triiodothyronine (90%) 16. T4-thyroxine (10%) 17. **Most T4 is converted to T3 which acts on the target cells to produce a response** xxxix. **Thyroid Hormone Actions** 18. Regulates protein, fat, carbohydrate catabolism 19. Metabolic rate of all cells 20. Insulin antagonist 21. Cardiac rate, force, output 22. GI tract secretion 23. Respiratory rate, oxygen utilization - **[Parathyroid]** xl. 4 parathyroid glands (posterior) -- two pairs on the upper/lower poles of thyroid gland xli. **Secretion influenced by:** 24. **Calcium levels (primarily)** h. Regulates serum calcium concentration - secretion is stimulated by a decrease in serum ionized calcium levels 25. **Magnesium levels** 26. **Phosphate levels** xlii. **Bone effects** 27. Mobilizes calcium release from bone (bone reabsorption), increasing serum calcium level xliii. **Kidney effects** 28. Acts on distal tubules to increase reabsorption of calcium (back to peritubular capillaries/serum) 29. Acts on proximal tubules to decrease reabsorption of phosphate and bicarbonate (keeps it in tubules) -- as calcium levels rise, phosphate levels drop 30. Stimulates the production of vitamin D - **[Pineal gland]** xliv. Located near center of brain, secreting melatonin xlv. Melatonin 31. Synthesized from tryptophan 32. Regulates circadian rhythms and reproductive systems, including onset of puberty 33. Release is stimulated by exposure to dark 34. Release is inhibited by exposure to light - **[Pancreas]** xlvi. Exocrine function -- produces digestive enzymes xlvii. Endocrine function -- produces hormones xlviii. Islets of Langerhans  - **[Adrenal gland]** xlix. Pyramid shaped organs above each kidney, surrounded by capsule embedded in fat l. Two separate portions 35. Cortex -- non SNS innervation 36. Medulla -- SNS innervation, releases epi and norepi 8. **Identify the physiologic functions of the adrenal glands, including:** - **[Cortex]** li. **[Zona glomerulosa]** 37. Outer layer 38. 15% of cortex 39. Aldosterone lii. **[Zona fasciculata]** 40. Middle layer 41. 78% of cortex -- largest portion 42. Glucocorticoids (cortisol, cortisone, corticosterone) liii. **[Zona reticularis]** 43. Inner layer 44. 7% of cortex 45. Mineralocorticoids, adrenal androgens, and estrogens, and glucocorticoids - **Medulla** liv. Chromaffin cells (pheochromocytes) 46. Stores and secrete epinephrine and norepinephrine lv. Direct SNS stimulation from pre-ganglionic sympathetic fibers lvi. Epi and norepi are synthesized from the amino acid phenylamine - **Catecholamine biosynthesis** lvii. Tyrosine hydroxylase is rate-limiting enzyme lviii. Responds to increasing levels of dopamine and norepinephrine in a negative feedback mechanism 9. **Describe the physiologic changes that occur with aging for the:** - Thyroid gland - Endocrine pancreas - Parathyroid glands - Adrenal glands **[Endocrine Pathophysiology]** 1\. **[Alterations ]** - **Inappropriate amount of hormone** - Inadequate hormone synthesis d/t inadequate precursors or unable to convert precursors to active hormone - Failure of feedback systems - Inactive hormones - Dysfunctional delivery systems d/t inadequate blood supply, inadequate carrier proteins, and ectopic production (hormone produced in wrong spot) - **Inappropriate response by target cell** - Cell surface receptor disorders - Receptor reduction - Impaired receptor function - Antibodies against receptors - Malfunctioning receptors - Intracellular disorders - Inadequate second messengers - Altered proteins or enzymes 2\. **Describe the alterations in the hypothalamic-pituitary system, and the physiologic manifestations of each.** - Most common -- interruption of pituitary stalk from lesions, head injury, surgical transection, tumor a\. **Hypopituitarism** - Inadequate supply of hypothalamic hormones - Damage to pituitary stalk - Inability of pituitary gland to produce hormones - **Causes:** - Pituitary adenoma -- suppressing cells so nothing can be secreted - Pituitary surgery or radiation - Pituitary infarction (Sheehan Syndrome) - Pituitary apoplexy - Aneurysms - Sickle cell disease - TBI - Infections - Sarcoidosis - Autoimmune hypophysitis - Medications - **Pituitary gland is HIGHLY vascular -- relies on portal blood flow from the hypothalamus (very vulnerable to ischemia and infarction)** - Infarction leads to tissue necrosis and edema/gland swelling - Sella turcica (protects the pituitary gland) is fixed in size -- expansion of the gland leads to compression of the pituitary blood supply and/or surrounding structures -- can cause otherwise normal cells to stop secreting - **Panhypopituitarism** -- all hormones are deficient - Cortisol deficiency - Thyroid deficiency - Lack of secondary sex characteristics - Poor growth in children or other s/s in adults - No lactation in postpartum women - **Evaluation** -- hormone measurements, CT/MRI to evaluate pituitary gland - **Treatment** -- correction of underlying cause, circulatory collapse -- glucocorticoids and IV fluids b**. Hyperpituitarism** - **Pituitary adenomas** - Usually benign, slow-growing - Microadenomas usually found on autopsy/incidentally on MRI - Macroadenomas and giant adenomas usually demonstrate s/s - Alterations in hormone secretion (hypersecretion from adenomas itself, or hyposecretion from surrounding cells) - Visual disturbances -- pressure on optic chiasm and optic nerve (visual field impairments and temporary blindness) - Headache - Fatigue - Neck pain/stiffness - Seizure - **Growth hormone excess: adults** - Nearly always due to GH-secreting tumor - In adults -- acromegaly - In children -- giantism - **Excess Growth hormone effects** - Increased cartilage growth - Bony proliferation - Metabolic changes - Inhibition of peripheral glucose uptake, increased production - Increased insulin secretion, insulin resistance - CV (htn, LVF, and cardiomyopathy) - Overactive sebaceous/sweat glands - Coarse skin and body hair - Effects of pituitary gland compression - **Prolactinoma** - Most common hormonally active pituitary adenomas - S/s: inhibition of GnRH, altered release of LF/FSH, gonadal steroidogenesis - Women: Amenorrhea, infertility, galactorrhea/prolacetinemia (milk production), excessive hair growth - Men: erectile dysfunction, infertility, osteopenia - **Evaluation** - Presence of clinical features - Visual field testing - MRI - Lab values - **Treatment Goals** - Normalize GH/IGF-1 levels - Surgical resection or radiation - s/s often improve with treatment except for skeletal changes **3. Disease of the Posterior Pituitary Gland** - **[SIADH ]** - High levels of ADH in the absence of normal physiologic release stimuli - ADH increases water reabsorption by the kidneys - Intracellular volume expansion, leading to dilutional hyponatremia, hypo-osmolality, and highly concentrated urine - Symptoms increase as serum sodium falls - Hypovolemia or increased osmolality stimulates ADH release - Due to: - Ectopic tumor production - Small cell carcinomas in gastric system - Uro-gyn cancers (prostate, bladder, endometrium) - Pulmonary disease (TB pna, small cell carcinoma, asthma, cystic fibrosis, respiratory failure requiring mechanical ventilation) - CNS disorders (encephalitis, meningitis, ICH, tumors, trauma from neurosurgery) - Transient SIADH common after pituitary surgery - Medications (especially in the elderly) - Hypoglycemics, anti-depressants, anti-psychotics, narcotics, general anesthetics, chemo drugs, NSAIDs, synthetic ADH - **[Diabetes Insipidus ]** - ADH insufficiency - Insufficient secretion of ADH or insufficient response to ADH in renal tubules - Insufficient ADH causes excretion of large volumes of dilute urine, increasing plasma osmolality - Thirst - Hypernatremia - Hyperosmolality - Other electrolytes not affected - **Clinical manifestations**: - Polyuria - Polydipsia - Nocturia - Urine output is varied (up to 12 L/day) - **Neurogenic DI** - Usually abrupt onset - Inadequate secretion of ADH - Interference with ADH synthesis, transport, release - Primary/metastatic brain tumors - Hypophysectomy - Aneurysms - Thrombosis - Infections - Immunologic disorders - TBI - Pregnancy complications - **Nephrogenic DI** - Usually gradual onset - **Inadequate response of the renal tubules to ADH; usually acquired but may be genetic** - Pyelonephritis - Amyloidosis - Destructive uropathies - Polycystic disease - Intrinsic renal disease - **Evaluation** - Water deprivation test - Differentiation between neurogenic and nephrogenic DI - Neurogenic DI responds -- increased ability to concentrate urine - Nephrogenic does not respond - **Treatment** - ADH replacement (desmopressin) -- if neurogenic DI - Fluid replacement - Discontinuing medications that may be contributory - Thiazide diuretics may help with water retention  **2. Describe the alterations in the thyroid gland that may predispose a patient to thyroid dysfunction**. - **[Primary thyroid disorders]** - Disease or dysfunction of the thyroid gland - Alterations in TH levels with secondary feedback effect on pituitary TSH levels - **[Secondary thyroid disorders]** - Disease or dysfunction of pituitary gland (TSH production) **3. Compare and contrast hypothyroidism and hyperthyroidism in terms of:** **[a. Thyrotoxicosis]** - Increased TH levels (any cause) - **Primary hyperthyroidism** - Graves' disease - Toxic multimodal goiter - Solitary toxic adenoma - Follicular thyroid carcinoma - **Secondary hyperthyroidism** - TSH-secreting pituitary adenomas - **Clinical manifestations:** - Increased metabolic rate - Heat intolerance - Increased tissue sensitivity to SNS stimulation - **Evaluation:** - Primary hyperthyroidism (increased T3 and T4 levels with decreased serum TSH levels) - Secondary hyperthyroidism (normal/increased TSH levels with elevated T3 and T4 levels) - **Treatment:** - Anti-thyroid medications - Radioactive iodine therapy - Surgery - Treatment complications include development of hypothyroidism **[b. Hypothyroidism ]** - **Primary hypothyroidism** - most common disorder of thyroid function - Decreased production of TH (T3 and T4) and increased secretion of TSH - Autoimmune thyroiditis (Hashimoto) - Iatrogenic after surgery or radiation - Head/neck radiation - Medications - Iodine deficiency - **Secondary hypothyroidism** - Related to pituitary or hypothalamic failure - Pituitary tumors - TBI - Subarachnoid hemorrhage - Pituitary infarction - **Clinical manifestations** - Low basal metabolic rate - Cold intolerance - Diastolic hypertension - Reduced TH levels can increase TSH, causing a goiter - **Myxedema** - Connective fibers are separated by increased protein and mucopolysaccharides, promoting non-pitting edema - Myxedema coma (medical emergency) -- precipitated by infections, d/c of thyroid medications, overuse of sedatives, acute illness with hypothyroidism - Diminished LOC - Hypoventilation - Hypotension - Hypoglycemia - Lactic acidosis - Coma - **Evaluation:** - Clinical s/s - Primary: increased levels of TSH and decreased levels of TH - Secondary: decreased levels of TH, with normal or low TSH - **Treatment:** hormone replacement therapy (Synthroid) **4. Describe the alterations present in the parathyroid gland, and the physiologic manifestations of each.** - **Hyperparathyroidism:** Excess secretion of parathyroid hormone and hypercalcemia - Primary -- PTH secreted in excess by the parathyroid gland - Secondary -- compensatory response to chronic hypocalcemia (CKD) - Tertiary -- develops after long-standing hypocalcemia (produces parathyroid cell hyperplasia and overproduction -- s/p renal transplant) - **Clinical manifestations: Hypercalcemia and hypophosphatemia** - Fatigue - Headache - Depression - Anorexia - N/V - Pathologic fractures - Kyphosis - Compression fractures of vertebral bodies - Calcium stones - **Evaluation:** - Primary: increased calcium and increased/normal PTH levels - Secondary: reduced calcium and high PTH levels - **Treatment:** - Primary: hydration, surgical removal of 1-3 glands (inadvertent removal often occurs with thyroidectomy) - Calcium replacement, phosphate restriction, vitamin D replacement - **Hypoparathyroidism** - Most commonly diagnosed by damage/removal of glands during thyroid surgery - **s/s:** - lower threshold for nerve and muscle relaxation - perioral numbness, paresthesia, tingling, tetany, laryngeal spasms (due to decreased Calcium) - Chvostek sign -- cheek twitching - Trousseau sign -- carpal pedal spasm - **Evaluation:** - Low calcium/high phosphate level - Low PTH level - **Treatment:** - IV calcium (acutely) - Oral calcium and vitamin D (chronic) - PTH hormone replacement **5. Compare Type I vs. Type II diabetes in terms of:** **a. causes** - Hyperglycemia -- insulin secretion defect, insulin action defect, or BOTH - **Type I** -- autoimmune beta cell destruction - Most common pediatric disease - Diagnosis peaks at age 12 - Insulin normally suppresses glucagon - Glucagon acts in liver to stimulate glycogenolysis and gluconeogenesis (breakdown of glycogen and production of glucose) - Amylin also suppresses glucagon release from alpha islet cells - **Type II** -- insulin resistance with relative insulin deficiency - Suboptimal response of insulin-sensitive tissues (liver, muscle, fat) - Associated with obesity - Risk factors: - Age - Obesity - Htn - Physical inactivity - Family hx - **Gestational diabetes** - Glucose intolerance during pregnancy - Both insulin resistance and inadequate insulin secretion are factors - Risks to pregnancy -- stillbirth, fetal macrosomia (big baby -- 4kg), neonatal hypoglycemia (baby producing own high levels of insulin), shoulder dystocia - **Diagnosed with:** - HGB A1C - Fasting plasma glucose in OGTT - Random glucose levels in symptomatic individuals b\. signs/symptoms - **Type I** -- long preclinical course of beta-cell destruction - Evaluation: many children are diagnosed when they present with DKA, diagnosis is made with lab value and concurrent symptomology - Treatment: focused on maintenance of normoglycemia---insulin therapy, exercise, meal planning, self-monitoring - **Type II --** - Treatment: - Maintain euglycemia (diet, oral hypoglycemic medications, insulin) - Weight loss improves insulin sensitivity and glucose tolerance, preserves remaining beta-cell function - Bariatric surgery **c. acute complications (DKA vs. HHNK)** - Hypoglycemia -- Type II is at less risk than Type I - **DKA** -- generally occurs in Type I diabetes more than Type II - Insulin deficiency + excess counterregulatory hormone levels - Without insulin, fat cells release fatty acids producing ketones faster than can be used (insulin deficiency) - Ketones produce metabolic acidosis - Total body hypokalemia significant, but may appear normal -- reflects volume contraction and extracellular shift (dehydrated patients) - ***Insulin deficiency is more profound in DKA -- why ketones are produced*** - **S/s:** - Kussmaul respirations - Postural dizziness - CNS depression - Ketonuria - Sweet breath - Anorexia - n/v - abdominal pain - polyuria - hypokalemia - **Labs:** - Glucose \>250 - Bicarbonate \320 - Absent or low levels of ketones in blood/urine - **Tx:** - Insulin infusion - Fluid replacement **-- fluid replacement is more rapid compared to DKA; increased fluid deficit** - Electrolyte replacement **- electrolyte deficiencies may be more extreme** **d. chronic complications** - **Causes of complications:** - Chronic hyperglycemia - Insulin resistance or deficit - Accumulation of advanced glycation end products (prayer sign) - Activation of damaging pathways - Oxidative stress - **Types of complications:** - **Microvascular** - **Retinopathies**: leading causing of blindness worldwide - **Diabetic kidney disease**: most common cause of CKD and ESRD - **Diabetic neuropathy**: most common cause of neuropathy, and common complication of diabetes - **Autonomic neuropathy**: GI nerves (delayed gastric emptying), bladder/sexual dysfunction, sweating, body temperature regulation, CV processes - **Charcot neuroarthropathy**: affects foot/ankle - **Macrovascular** - **CV disease** -- silent MI (esp, in women) - **Stroke** -- twice as common in diabetics, esp in women - **Peripheral artery disease** - **Infection** - Sensory alteration - Hypoxia - Pathogenic environment - Reduced blood supply (WBC delivery) - Suppressed immune response - Delayed wound healing **6. Identify the pathologies that occur with hyper- and hypo- function of the adrenal gland, including causes, expected lab values and side effects of:** **a. Adrenal Hyperfunctioning** - **Hypercortisolism -- Cushing disease** - Excess endogenous secretion of ACTH, causing high levels of cortisol production - ACTH-dependent hypercortisolism (most commonly d/t pituitary adenoma) - ACTH-independent hypercortisolism (caused by adrenal tumor) - **S/s:** - Truncal obesity (buffalo hump, moon face) - Glucose intolerance (insulin resistance) -- hyperglycemia - Muscle wasting - Osteoporosis - Hypertension - Easy bruising - **Evaluation:** - Tumors diagnosed using imaging - Serum ACTH levels - Urinary and serum cortisol levels - **Treatment:** - Specific to the cause - Medication - Radiation - Surgery - W/o treatment, prognosis is poor -- 50% die within 5 year without treatment - Infection - Suicide - HTN - Arteriosclerosis - **Hyperfunction of adrenal androgens -- virilization (androgens) or feminization (estrogens)** - Adrenal tumors - Endogenous hypercortisolism - Defects in steroid synthesis - **Androgen-secreting tumors:** - Excess body hair - Clitoral enlargement - Deepening of voice - Amenorrhea - Acne - Breast atrophy - **Estrogen-secreting tumors:** - Gynecomastia (increased breast tissue in men) - Testicular atrophy - Decreased libido - **Hyperaldosteronism -- Conn syndrome** - Excessive aldosterone secretion by the adrenal cortex - Primary hyperaldosteronism -- Conn syndrome - Secondary hyperaldosteronism -- excess secretion from an adrenal stimulus - Renin secretion suppressed in primary, elevated in secondary - **S/s:** - HTN - Hypokalemia - Hypervolemia (increased sodium reabsorption) - Metabolic alkalosis - **Evaluation:** - HTN sensitivity - Electrolyte levels (Serum sodium, potassium, urinary potassium) - Aldosterone-renin ratio - Aldosterone suppression testing - Imaging for tumors - **Tx:** - Management for HTN and hypokalemia - Surgery for tumors - ACE and ARB for secondary disease **b. Adrenal Hypofunctioning** - **Hypocortisolism/Adrenal insufficiency -- Addison's disease** - **Primary -- Addison's disease** - Inability to synthesize/secrete adrenocortical hormones (both cortisol and aldosterone) - Auto-immune destruction of adrenal cortex OR infections, infiltrative diseases or adrenal hemorrhage - Inadequate glucocorticoid and mineralocorticoid synthesis, combined with elevated ACTH levels (d/t loss of negative feedback) - More common in women - **S/s:** - Weakness, fatigue - Skin changes - Anorexia, N/V, diarrhea - Hypovolemia - Postural hypotension - Dizziness - Dehydration - Hyperkalemia - Salt craving - **Evaluation:** - Reduced cortisol levels with increased ACTH - Hypoglycemia - Hyperkalemia - **Treatment:** - Lifelong replacement of glucocorticoids and mineralocorticoids - Additional replacement during times of stress -- give steroids up front before surgical stress - **Secondary** - Inadequate stimulation by ACTH - Caused by chronic administration of steroids -- causing ACTH levels to decrease - Adrenal glands atrophy over time - Renin-angiotensin system is functional, so aldosterone levels usually are normal - **Tertiary** - Abrupt withdrawal of exogenous glucocorticoids -- profound hypotension - **If on long term steroids, patient stops producing ACTH/adrenal gland suppressed-- steroid taper required** **7. List the diseases commonly associated with pheochromocytoma and paragangliomas.** - Catecholamine-secreting tumors - Associated with von Hippel Lindau, MEN-2, and neurofibromatosis-1 - 10-20% are malignant - **S/s:** r/t to catecholamine excess - HTN - Headache - Sweating - Palpitations - Tachycardia - ***Women are usually not dx right away -- think its anxiety*** **8. Identify the lab tests useful in the diagnosis of pheochromocytoma.** - **Evaluation:** - Increased catecholamines in blood (plasma metanephrines and urine metanephrines) -- byproducts of metabolism of catecholamines - Imaging to determine tumor location, surgical resectability - Genetic testing - **Management:** - Tx of catecholamine excess - **Alpha blockers -- given first (afterload reduction)** - **Beta blockers -- given second (can go into HF, if you do not reduce afterload because BB reduces contractility, Hr, and BP)** - Calcium channel blockers - Surgery **9. Compare and contrast android vs gynoid obesity in terms of fat distribution and associated risks.** - White adipose tissue -- most of adipose tissue in body -- considered an endocrine organ (adipokines) - Circulates in the blood, increase or decrease in relation to body fat mass - Provide signals to the hypothalamus, brainstem, and ANS - Control of food intake/energy expenditure - Lipid storage - Insulin sensitivity - Immune and inflammatory responses - Coagulation - Fibrinolysis - Angiogenesis - Fertility vascular homeostasis - Blood pressure regulation - Bone metabolism - Acute energy surplus -- excess calories (Mature WAT cell hyperplasia and adipogenesis -- increase in \#) - Chronic energy surplus -- mainly on WAT cell hyperplasia (bigger) - Complications of obesity are r/t where the fat is stored not just the amount of fat storage - **Visceral obesity (android)** - Distribution is around the abdomen and upper body - Apple shaped - Increased risk of metabolic syndrome, OSA, DM II, CV Complications, cancer - More men - **Peripheral obesity (Gynoid)** - Distribution is around hips, thighs, buttocks - Pear-shaped - Less metabolically active - Risk factors less severe than those for visceral obesity - More women - Obesity risk factors for other diseases: HTN, Stroke, HLD, gallstones, GERD, hiatal hernia, infections, asthma, OSA, CKD - **Evaluation:** - Height/weight/BMI - Weight-to-hip ratio - Above 0.90 for men - Above 0.85 for women - Skinfold thickness - Ultrasound - Bioelectric impedance - **Tx:** - Diet, exercise, modification of any metabolic disturbances - Bariatric surgery shows to have most significant reduction of comorbidities and insulin resistance **10. Other Nutritional Disorders** - **Starvation** - Decreased calorie intake - Short term -- glycogenolysis (splitting of glycogen into glucose), gluconeogenesis (formation of glucose from non-carbohydrate molecules) - Leads to ketosis and acidosis - Long term -- marasmus, kwashiorkor (protein deficiency) - **Anorexia of Aging** - Reduced energy needs - Decreased production of saliva - Medications - Co-morbidities - Delayed gastric emptying/decreased gastric motility - Sensory impairments - Medical/psych disorders **Quiz Questions** 1\. Antidiuretic hormone secretion may be stimulated by a(n): **Reduction in intravascular volume** 2\. In a normal physiologic state, increasing levels of thyroid hormones will cause: **Decrease in thyrotropin-releasing hormone secretion and Decrease in thyroid-stimulating hormone secretion** 3\. Secretion of parathyroid hormone is stimulated by a reduction in: **Serum calcium levels** 4\. The portion of the of the adrenal gland that secretes the glucocorticoids is the: **Zona fasiculata** 5\. Which clinical sign is consistent with a diagnosis of diabetes insipidus? **Low urine specific gravity** 6\. Laboratory values consistent with a diagnosis of hypothyroidism include: **Increased TSH and decreased TH** 7\. The most critical management component of a patient with a secreting adrenal medulla tumor includes the administration of: **Anti-hypertensives** 8\. Which clinical sign or symptom is consistent with a diagnosis of Addison's disease? **Hypovolemia** 9\. Which lab value is consistent with a diagnosis of diabetes mellitus? **8 hour fasting glucose 140md/dL** 10\. Diabetic neuropathy usually presents: **in the hands and feet** 11\. Which condition is associated with the development of syndrome of inappropriate antidiuretic hormone (SIADH)? **Small cell carcinoma of lungs** **[Describe the physiology and pathophysiology of the reproductive system during fetal development, puberty, and in the aging individual.]** - Structure and function of reproductive systems are dependent on steroid hormones called **sex hormones** - Steroid hormones are grouped into two classes: **corticosteroids and sex steroids** - **Five types according to the receptors to which they bind:** - testosterone (androgen) - Estradiol (estrogen) - Progesterone (progestin) - Cortisol/corticosterone (glucocorticoid) - Aldosterone (mineralocorticoids) - Early in embryonic development reproductive structures of male and female embryos homologous -- **every embryo has both at the beginning** - One pair of gonads and two pairs of ducts = Wolffian ducts and Mullerian ducts - Gonad= an organ that produces gametes- a testis or ovary - **Mullerian = internal female sex organs** - **Wolffian = male internal sex organs** - Embryogenesis, the first eight weeks of development after fertilization +-----------------------------------+-----------------------------------+ | **Male differentiation (XY):** | **Female differentiation (XX):** | +-----------------------------------+-----------------------------------+ | - 6-8 weeks gestation | - 6-8 weeks gestation | | occurrence | occurrence | | | | | - Male embryo differentiates | - Absence of SRY gene | | under influence of | expression- no signal from | | ***testes-determining factor | the Y chromosome -- no | | (TDF**), a protein expressed | testes-determining factor | | by the SR**Y** **gene*** | (TDF) | | | | | - By 8 weeks TDF stimulates | - Needs *presence of estrogen* | | male gonads to develop into | and absence of testosterone | | testes- testosterone | and MIH-\> loss of Wolffian | | secretion begins | ducts | | | | | - **Mullerian inhibitory | - Loss of wolffian ducts allows | | hormone (MIH) secreted by | the **Mullerian ducts to | | Sertoli** cells in testes = | join** and become the uterus, | | NO mullerian ducts | fallopian tubes, cervix, and | | | upper two thirds of vagina. | | - **Wolffian duct remains.** | | +-----------------------------------+-----------------------------------+ - **External sexual differentiation** - External structures develop from homologues tissues - **During the first 7-8 weeks gestation all embryos develop an elevated structure called the genital tubercle** - **Testosterone is necessary for genital tubercle to differentiate into male genitalia; otherwise female develop** - **Gametes= reproductive cells** - **Female gametes**= ova or egg cells - **Male gametes**= sperm cells - Ova and sperm are haploid cells, each cell carries only one copy of each chromosome - **Females**= all primary oocytes (potential to become secondary oocytes through menstrual cycle and ovum through fertilization) present in the ovaries at birth. - **Bicornuate uterus -** failure of fusion of mullerian ducts = heart shaped uterus and can impact infertility. - **Males**= sperm development begins at puberty and continues lifelong - Congenital absence of a testicle - Undescended testes usually self resolve around one year or can get surgical procedure to bring down testes. - Hypospadias can impact urination **[Identify the functions of reproductive hormones]** **Production of GnRH in hypothalamus** **\*DON'T WORRY ABOUT DHEA AND INHIBIN\*** - **What is the function of GnRH in females?** - In the [[female reproductive system]](https://my.clevelandclinic.org/health/articles/9118-female-reproductive-system), GnRH indirectly stimulates your body's production of [[estrogen]](https://my.clevelandclinic.org/health/articles/16979-estrogen--hormones) and progesterone. These are the predominant female sex hormones that play a key role in [[ovulation and conception]](https://my.clevelandclinic.org/health/articles/11585-pregnancy-ovulation-conception--getting-pregnant) - **What is the function of GnRH in males?** - In the [[male reproductive system]](https://my.clevelandclinic.org/health/articles/9117-male-reproductive-system), GnRH stimulates the production of: - Luteinizing hormone, which affects how much [[testosterone]](https://my.clevelandclinic.org/health/articles/24101-testosterone) and [[androgens]](https://my.clevelandclinic.org/health/articles/22002-androgens) (male sex hormones) your body makes. - Follicle-stimulating hormone, which affects sperm production **[Hypothalamic Pituitary Cycle]** Beginning of the Hypothalamic Pituitary Gonadal (HPG) axis Occurs in BOTH men and women - HPG axis responsible for development and maintenance of - Secondary sexual characteristics - Menstrual cycle in females - Puberty completes at the first ovulatory menstrual period. - Spermatogenesis in males - Production of mature sperm ***[Puberty]*** - Prior to puberty, the pituitary becomes more responsive to the release of GnRH by the hypothalamus - **Increased production of estrogen and testosterone leads to development of secondary sex characteristics** - Adrenarche-- adrenal contribution- increased production of adrenal androgens-- converted to estrogen and testosterone and related to pubic and axillary hair growth and increased sweat glands (secondary sex characteristics - Male: - Testes begin to produce mature sperm - Puberty complete with first ejaculation of mature sperm - Determine puberty based on secondary sex characteristic development - Female: - Ovaries begin to release mature ova - Puberty complete at first ovulatory menstrual period - Determine puberty based on secondary sex characteristic development - Delayed puberty - Psychosocial implications - Skeletal development -- lack of estrogen/testosterone leads to inadequate bone density - Hormonal or genetic causes - Precocious puberty -- young age at which puberty starts - Psychosocial implications - Skeletal development -- premature closure of epiphyses leads to short stature - Differing hypotheses of causes **[Ovarian Cycle]** - **Ovaries** - Female gonads - Primary female reproductive organ - Secrete female sex hormones- estrogen and progesterone - Develop and release female gametes - Almond-shaped organs on both sides of uterus - Medulla- inside - Cortex- outside that contains ovarian follicles, theca cells, and granulosa cells - Ovarian follicles continuously grow and undergo atresia *(degeneration of the ovarian follicles which do not ovulate during the menstrual cycle)* - Typically, only 1 of the follicles reaches maturation and discharges its oocyte each menstrual cycle - Rest of follicles either fail to develop or degenerate without complete maturation - After ovulation, the "chosen" follicle develops into corpus luteum - IF fertilization occurs, corpus luteum enlarges and secretes hormones that maintain and support pregnancy - **If fertilization does NOT occur, then the corpus luteum degenerates,** which triggers the maturation of another follicle. - In the ovary, all ova are initially enclosed in a single layer of cells known as a follicle, which supports the ova. **During the follicular phase *(first part of the menstrual cycle)*, one or two ovarian follicles grow due to the action of FSH** - This is why absence of menses is suspicious for pregnancy- especially in reproductive years *(roughly age 19-menopause)* but also in age 13-18 as they are capable of reproduction *(but keep in mind though that irregularity within first year of menses is expected, related to expected anovulation in adolescence)* - Process of follicular maturation, ovulation, corpus luteum development and corpus luteum degeneration - Occurs from puberty to menopause - Ceases at menopause - Stops during pregnancy or hormonal contraceptive use (some types) **[Reproductive Hormones]** - Male and female sex hormones present in all adults - Female body contains lower levels of testosterone and other androgens - Male body contains lower levels of estrogen - Dominant female sex hormones, **estrogen and progesterone**, produced primarily in ovaries - Different types of estrogen - During fetal development, infancy, and childhood sex hormone production low - At puberty sex hormone production surges - From puberty to menopause the sex hormones control the menstrual cycle and are produced cyclically - NOT to be confused with gonadotropic hormones (**follicle stimulating hormone (FSH) and luteinizing hormones (LH)**- those are synthesized and released by the anterior pituitary, which act on the gonads (testes or ovaries) to increase production of sex hormones. - **ALSO want to mention that estrogen has nonreproductive effects such as maintaining bone density, acting in liver to decrease cholesterol level, etc... table in book on page 24.1 if curious! Explains why postmenopausal women have different risks associated with low estrogen.** **[Discuss the normal menstrual cycle]** Menstruation consists of phases in ovaries: **Menstrual cycle is 28 days total** - **Follicular (first 14 days of cycle)** - (Ovulation)- not a phase on its own, but an important event in between phases - **Luteal/secretory phase (last 14 days of cycle)** - During menstruation the functional layer of the endometrium disintegrates and is discharged through the vagina +-----------------------+-----------------------+-----------------------+ | **Follicular Phase** | **Ovulation** | **Luteal Phase** | +-----------------------+-----------------------+-----------------------+ | Approximately **days | Most fertile days. | - - - - | | 1-14 of menstrual | | | | cycle** | Last 16-32 hours | - - | | | | | | - - - - - | Move along fallopian | - - | | | tube → uterus | | | | | | | | - - - | | | - - - - - - | | | | | | | | | | | | NOTE: Feedback loops | | | | activated have to do | | | | with concentration of | | | | estrogen. At LOW or | | | | steady concentrations | | | | of increasing | | | | estrogen LH & FSH are | | | | inhibited (negative | | | | feedback) | | | | | | | | BUT as maturing | | | | follicle continues to | | | | secrete estrogen, | | | | estrogen | | | | concentrations rise | | | | higher, and at HIGH | | | | concentrations | | | | estrogen STIMULATES | | | | LH and FSH secretion | | | | (positive feedback) | | | | Only Positive | | | | feedback in | | | | reproductive | | | +-----------------------+-----------------------+-----------------------+  **[Discuss spermatogenesis]** - GnRH secretion by hypothalamus - Stimulates the anterior pituitary to secrete LH and FSH - **LH stimulates testosterone secretion from the Leydig cells** - Testosterone inhibits GnRH and LH secretion - Sex production is continuous in male and variable in females - **Testosterone stimulates the growth & proliferation of** **germ cells** & takes place in seminiferous tubules present inside the testes - At puberty mitosis causes spermatogonia to become a primary spermatocyte→ secondary spermatocyte→ spermatid→ spermatozoa - Maturation takes approximately 70-80 days - Motility requires activation by biochemicals in semen and in the vagina - **GnRH stimulates FSH and LH →FSH stimulates Sertoli cells to induce** **spermatogenesis** - Sertoli cells also produce inhibin→ negative feedback that inhibits FSH **[Describe the pathophysiology of menstrual abnormalities]** - **Dysmenorrhea** - Primary or secondary - **Primary dysmenorrhea** - **Caused by prostaglandin release in ovulatory cycles** - No evidence of organic pathophysiology in the uterus, fallopian tubes, or ovaries. - Multiple symptoms - in addition to pain in abdomen, back, legs may also have temperature fluctuations, diarrhea, fainting, etc. - Prostaglandins have a role in the natural physiology of your body in addition to their role in defense and repair - Prostaglandins are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects - Prostaglandins are responsible for uterine contractions during menstruation. These contractions help release the uterine lining (endometrium) from your uterus, thus producing a period. - **Secondary Dysmenorrhea:** painful menstruation related to pathology - Example endometriosis- a disease in which tissue like the lining of the uterus grows outside the uterus. It can cause severe pain in the pelvis and make it harder to get pregnant - **Amenorrhea** : **Most common cause is pregnancy** - **Absence of menses at any age when menstrual function should be present** - **[Primary - no menstruation:]** - By age 14 years without the development of secondary sex characteristics - By age 16 years regardless of the presence of secondary sex characteristics - **[Secondary - no menstruation:]** For a time equivalent to 3 or more cycles in those who have previously menstruated - ANYTHING that disrupts the HPG axis - Dramatic weight loss, malnutrition, excessive exercise, thyroid dysfunction, PCOS, chemotherapy, and much more - **Physiologic in early adolescence, perimenopause, menopause, pregnancy, and lactation** - **[Endometrial Disruption -- Amenorrhea ]** - ***Asherman syndrome*** - (Intrauterine adhesions or intrauterine synechiae) occurs when scar tissue forms inside the uterus and/or the cervix. These adhesions most commonly occur after surgery of the uterus - ***Endometrial ablation*** - Goal is to reduce how much you bleed during periods, also called menstrual flow. Typically electric current is used to thin layers of the endometrium - ***Contraception side effect (hormonal IUD)*** - Levonorgestrel (a progestins, or progestogen- a class of synthetic hormone drugs that mimic progesterone\'s endogenous hormone) thins the endometrium, there is less of this material to shed so periods may be lighter and briefer periods. - **Abnormal Uterine Bleeding** - Vaginal bleeding separate from normal, cyclic menstrual flow - Duration: Bleeding lasting longer than 7 days - Frequency: Occurring more frequently than every 21 days - Regularity: Intermenstrual spotting or bleeding or bleeding after intercourse - Any bleeding or spotting after 12 months of amenorrhea in menopausal age individual - Any of these things could be considered abnormal uterine bleeding - **Does not include volume**- heavy but regular bleeding requires minimal evaluation, often called menorrhagia **[Aging of female reproductive system]** - **Decline in fertility and increase in spontaneous abortion starting at age 35, greatly increases by age 40** - Decrease in ovarian size - Increase in anovulatory cycles - Decreased breast density - Atrophic changes - **Perimenopause: ​​Patients may begin experiencing symptoms of perimenopause approx. 5 years prior to onset of menopause** - Elevated FSH leads to ovarian hyperstimulation - Increased follicle recruitment and loss - Decreased follicular reserve - Elevated estrogen - Decreased progesterone - **Menopause: Cessation of ovarian function** - Average age 51 - Defined as 12 months of amenorrhea - Elevated FSH - Decreased estrogen, progesterone, and testosterone - produces less estrogen than it used to. This increases the risk of the coronary arteries narrowing whereas it previously protected the lining of the artery walls reducing the build-up of plaque. - drop of estrogen leads to more bone resorption than formation, resulting in osteoporosis. The major health threat of osteoporosis is osteoporotic fractures. - **UTI frequency related to changes in vaginal tissues and pH changes r/t loss of estrogen**- As you age, your vaginal tissue thins, making it more prone to infection. You may also have trouble fully emptying your bladder, which can increase the chance of an infection in your bladder - Vasomotor symptoms - Increase in health risks - largely related to lack of estrogen- such as cardiovascular (heart) disease, osteoporosis (weak bones) and urinary tract infections (UTIs) **[Aging of Male Reproductive System ]** - **Hypogonadism:** Testes are producing less testosterone - **Primary.** This type of hypogonadism --- also known as primary testicular failure --- originates from a problem in the testicles. - **Secondary.** This type of hypogonadism indicates a problem in the hypothalamus or the pituitary gland --- parts of the brain that signal the testicles to produce testosterone. The hypothalamus produces gonadotropin-releasing hormone, which signals the pituitary gland to make follicle-stimulating hormone (follicle-stimulating hormone (FSH)) and luteinizing hormone (luteinizing hormone (LH)). Luteinizing hormone then signals the testes to produce testosterone. - Increased incidence erectile dysfunction - **Proliferative disorders of the prostate** - **Benign prostatic hyperplasia (BPH),** also known as benign prostatic hypertrophy, is a histologic diagnosis characterized by proliferation of the cellular elements of the prostate, leading to an enlarged prostate gland - BPH occurs when both stromal and epithelial cells of the prostate in the transitional zone proliferate by processes that are thought to be influenced by inflammation and sex hormones, causing prostate enlargement **[Identify the pathophysiologic mechanisms of common reproductive system abnormalities]**  **[PALM: Structural Causes]** How would we evaluate structural causes? Pelvic ultrasound (typically transvaginal) - ***[Polycystic Ovarian Syndrome]*** - Complex and multidimensional disorder **caused by insulin resistance** that can cause amenorrhea, infertility, and defects in metabolism - 4-12% of reproductive age - Polycystic ovaries (imaging finding) seen in 21-23% of individuals without PCOS and are no longer considered pathologic - Genetic component - Long-term sequelae include metabolic syndrome, dyslipidemia and endometrial hyperplasia - Imaging not needed to diagnose PCOS - **Pathogenesis of PCOS** - Hyperinsulinemia: 50-70% of those with PCOS - **Increased insulin levels in the blood because of mutation in CYPA11A (insulin receptor gene)** - Less sensitive →insulin does not bind as readily - Higher levels of serum insulin suppress sex hormone binding globulin (SHBG binds tightly to 3 sex hormones found in both males and females. *SHBG carries these 3 hormones throughout your blood)- higher levels of sex hormones circulating in free state* - Estrogen - Dihydrotestosterone (DHT) - Testosterone - ***PCOS: Patient Presentation*** - Menstrual irregularity - Secondary amenorrhea - Oligomenorrhea: abnormal menstruation that involves infrequent periods- may regularly go for longer than 35 days between periods - AUB - **Hyperandrogenism** - Hirsutism: excess hair growth, commonly on face - Male pattern baldness - Acne - **Infertility** - **Central Obesity** - 44% *with* increased waist:hip ratio) - **Acanthosis Nigricans** - Hyperkeratosis & increased skin pigmentation - Velvety plaques on neck, axilla, groin - Also seen in T2DM or obesity because of insulin resistance - **Miscarriage** - First-trimester SAB is reported in 30% **[Female Infection/Inflammation]** - Self cleaning - Acid-base balance discourages proliferation of many pathogenic bacteria - At puberty pH becomes more acidic and squamous epithelial lining thickens -- sustained until menopause - **Contains lactobacillus acidophilus** - Harmless resident bacteria that maintain acidic pH - Conditions that cause vaginal pH to rise lowers vaginal defenses against infection -- destruction of L. acidophilus from antibiotics, low estrogen levels, certain vaginal sprays - ***Vulvitis:* Inflammation of the female external genitalia** - Causes: Contact with soaps, detergents, lotions, hygienic sprays, shaving, menstrual pads, perfumed toilet paper, or non-absorbing or tight-fitting clothing - Vaginal infections that spread to the labia - ***Vaginitis -- most common*** - 3 Primary infections: - Bacterial Vaginosis -- overgrowth of lactobacillus - Candida Albicans - fungal CYP51 needed for cell wall integrity - Trichomoniasis - Acidic nature of vagina provides some protection - pH increases after menopause, increasing risk of infection - ***Cervicitis:* Inflammation or infection of the cervix** - Gonorrhea and Chlamydia - Mycoplasma Genitalium - Mycoplasma genitalium is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans - Mycoplasma genitalium [is not currently] recommended as part of the routine screening for STIs, likely due to prevalence. - ***Pelvic Inflammatory Disease (PID):* Acute inflammation caused by infection** - May involve [any organ] of reproductive tract - Cervicitis - Endometritis - Oophoritis -- infection of ovaries - Salpingitis -- infection of fallopian tubes - [Polymicrobial infection -] sexually transmitted or normally occurring bacteria migrate from the vagina to the upper genital tract - If untreated, can cause abscess, scarring, chronic pelvic pain, and infertility - Cervicitis that\'s caused by gonorrhea or chlamydia can spread to the uterine lining and the fallopian tubes, resulting in pelvic inflammatory disease (PID), - More advanced infection - ***On physical exam movement of the cervix is VERY painful- chandelier sign* - PID** **Female Benign Growths and Pathologic Processes** - ***Simple vs Complex Ovarian Cysts*** - Thin-walled cyst, fluid-filled. Cysts \< 3cm in size are normal - 4-7% have cysts \> 3 cm in size - Produced when an ovarian follicle or a number of follicles are stimulated but no dominant follicle develops and reaches maturity - **Complex cysts contains blood, mucus, septa, or solid components -- of more concern than simple cysts** - Complex: - Much less common than simple cysts - Can result from bleeding into cyst or other disruption in formation of a simple cyst - ***Polyps*** - **Endometrial** - Benign mass of endometrial tissue - Common cause of intermenstrual or excessive menstrual bleeding - Malignancy is rare - **Cervical** - Often visible with speculum exam - Common cause of cervical bleeding - Typically easy to remove and benign - ***Leiomyomas*** - ***Commonly called uterine fibroids*** - *Incidence in US for ages 35-49 - 40-80%, mostly asymptomatic* - *[Benign tumors] of smooth muscle cells in the myometrium* - *Cause abnormal uterine bleeding, pain, and symptoms related to pressure on nearby structures* - *Black females 4 X as likely to develop fibroids as White females, and twice as likely as those of Hispanic ethnicity* - *Black females have earlier age of onset, larger size of tumors and more severe symptoms* - *Link between vitamin D deficiency and fibroids* **[Female Reproductive cancers]** - **Endometrial**-- symptomatic with abnormal uterine bleeding, typically post menopausal bleeding - **Ovarian**-- typically asymptomatic until late. No screening test - **Cervical**-- Screening with Pap and/or HPV test-- associated with HPV - **Vulvar/vaginal**-- usually skin changes **[Male Reproductive System -- Infections/Inflammation ]** - **External genitalia:** - **Testes** - Essential organs of reproduction in male - Produce gametes (sperm) - Produce sex hormones - Dominant male sex hormones: testosterone - Suspended outside the pelvic cavity - Sperm production requires an environment slightly cooler than body temperature - **Seminiferous tubules-** site of sperm production (**spermatogenesis)** - **Leydig cells-** produce androgens, mainly testosterone - **Epididymis** is linked to vas deferens- sperm is stored here, multiple muscular layers capable of peristalsis that transports sperm toward urethra - **Penis erectile reflex** - Corpora cavernosa and corpus spongiosum become engorged with blood - **Parasympathetic nerves cause arterioles to dilate through release of nitric oxide** - **Male Internal Genitalia** - Prostate gland, two seminal vesicles, and two Cowper (or bulbourethral glands) - Secrete fluids for sperm transport; create alkaline, nutritious medium for sperm motility and survival. - Surrounds the urethra - some of the symptoms associated with BPH from hypertrophy - Ejaculatory duct formed by the union of the vas deferens with the duct of the seminal vesicles - Semen is composed of sperm and glandular fluids - **Urethritis** - Usually infectious (chlamydia or gonorrhea) may be non-infectious - May be accompanied by urethral discharge - Cystitis less common in males - ***Epididymitis:*** Inflammation of the epididymis - Typically occurs in sexually active males - **Pathology** - Sexual transmission of intestinal bacteria or *Pseudomonas aeruginosa* in the urinary tract - Pathogen reaches the epididymis and ascends to the vas deferens then to urethra and bladder - Acute and severe scrotal or inguinal pain is caused by inflammation of epididymis - Clinical signs: pyuria, bacteriuria, and urethral discharge - ***Orchitis: Acute inflammation of the testes (rare)*** - A complication of systemic infection or epididymitis - In post-pubertal males, Mumps is the most common infectious cause (ages 15-29 most common) - **30% of affected testes will have irreversible damage resulting in impaired spermatogenesis** - ***Prostatitis: Inflammation of the prostate gland and excretory ducts*** - ***Acute bacterial*** - *Ascending infection of Coliform bacteria* - *Affects those 30-50 years of age* - *Associated with benign prostatic hyperplasia* - ***Chronic bacterial*** - *Recurrent UTIs and persistence of bacteria* - ***Nonbacterial*** - *Most common* - *Inflammation without infection* **[Other Male Reproductive Issues ]** - ***Urethral Stricture*** - *Fibrotic narrowing of urethra d/t numerous foleys* - *Numerous causes, can occur at any age* - *Symptoms are of lower urinary tract issues* - ***Phimosis*** - *Foreskin too tight to be moved over penis -- normal in infancy up to age 3* - ***Peyronie Disease*** - Fibrotic condition causing curvature and sexual dysfunction - ***Priapism*** - *Prolonged, painful, erection* - ***Testicular Torsion*** - *Twisted blood vessels of the spermatic cord* - *Vascular engorgement and ischemia causing acute swelling and pain in scrotum* - *Most common in newborns up to young teens, but can occur at any age* - *Surgical emergency* - ***Benign Prostatic Hyperplasia (BPH)*** - ***Enlargement of prostate by an increase in the number of cells** (increased reproduction rate)* - *Common with aging* - *50% at age 60 and 90% at age 70+* - *Pathophysiology is multifactorial and involves an imbalance of growth factor signaling pathways* - *Not associated with cancer* - *Symptoms* - *Urinary frequency* - *Delay in starting urine stream* - *Decreased force of urine stream* **[Male Reproductive Cancers ]** - **Penile** - Rare - most in those over age 55 - Associated with HPV - **Testicular** - most common cancer in males between ages 15-35 - Cure rate \>90% - **Prostate** - Associated with advanced age, 1 in 6 by age 85 - 14% of all cancer deaths in males - Genetic and epigenetic mechanisms - **Estrogens and androgens act as tumor promoters** - Infection and chronic inflammation - Physical trauma - Environmental factors **[Sexual Dysfunction and Infertility]** - ***Sexual Dysfunction*** - Disorders of Desire-- decreased libido - Multifactorial-- need to establish diagnosis before treatment - **Anorgasmia--** often requires early referral to sex therapy - **Dyspareunia**-- may be associated with decreased estrogen in the female (loss of lubrication and subcutaneous tissue), peyronie's disease in the male, trauma, inflammation, or infection - **Erectile Dysfunction (ED)** - Inability to develop & maintain an erection in the absence of an ejaculatory disorder (e.g., premature ejaculation) - Prevalence of the condition increases with advanced age -- 40% at age 40 - Risk factors include heart disease and diabetes - ***Infertility*** - Incidence approximately 10-15% - Multifactorial (female or male cause) **[Breast issues]** - ***Galactorrhea:*** Persistent leakage of milky fluid when not lactating - Causes include: - Repetitive friction -- can be elicited by expression - Pituitary abnormality (tumor) - Medications (OCPs, psychotropics, metoclopramide) - Hypothyroidism - Stress - Trauma - Herpes zoster - Idiopathic - May continue to leak breast milk w/ pressure approx. 12 months following cessation of breast feeding- not abnormal - **Typically from too much prolactin, produced by pituitary gland** - **Prolactin is a polypeptide hormone that is responsible for lactation, breast development, and hundreds of other actions needed to maintain homeostasis** - Dopamine (a brain chemical) and estrogen (a hormone) control prolactin production and release from your pituitary gland - Your central nervous system, immune system, uterus and mammary glands are also capable of producing prolactin - The regulation of prolactin secretion is exerted by the hypothalamus, and involves the action of a prolactin-inhibiting factor (PIF), a possible prolactin-releasing factor (PRF), catecholamines, serotonin, **[Benign Breast Masses]** - **Fibrocystic breast changes are benign.** **[Breast Cancer: can happen to female and males]** - Incidence 1 in 8 in the U.S - **Invasive ductal carcinoma** - Most common type - Suspicious masses are hard and fixed with irregular borders - **Paget's disease** - Rare 1%-4% - Eczematous skin changes of nipple and areola, itching, redness, nipple discharge - Often with ductal or carcinoma in situ - **Inflammatory breast cancer** - Rare 1%-5% - Rapidly progressing - Erythema, edema, warmth, skin thickening and peau d'orange - May or may not have palpable mass - **Breast cancer risk factors:** - BRCA and other cancer gene mutations - First degree relative - Nulliparity or first child before age 30 - Not breastfeeding - Increased breast density - Breasts are typically less dense after menopause - Increased density is an independent risk factor for cancer as well as potentially masking a mammographic abnormality - Postmenopausal progesterone use - Environmental factors - Genetics and epigenetics **In-Situ Cancers** - **Ductal carcinoma in situ (DCIS)** - cancer cells replace normal ductal cells - Non-invasive form - Increases risk of invasive 2-fold - **Lobular carcinoma in situ (LCIS)** - cells look like cancer cells, but are benign - Increases risk of developing cancer by 4-fold **Quiz Questions**: 1\. Sperm and egg production are controlled **by: GnRH from the hypothalamus and FSH/LH from the pituitary** 2\. Benign Prostatic Hyperplasia is caused by an increase in prostate cell: **Number** 3\. True or False: Progesterone is the dominant hormone in the second (luteal) phase of the menstrual cycle. **True** 4\. True or False: Fibrocystic changes in the breast are associated with breast cancer. **False** 5\. Which of the following conditions would cause vaginal pH to rise thus lowering vaginal defenses against infection: **Destruction of Lactobacillus acidophilus from antibiotic therapy** 6\. Which of the following is TRUE about ovulation: **It occurs after 2-3 days of high estrogen concentration creates a surge in LH and FSH** 7\. A common müllerian duct abnormality is:  **Bicornuate uterus** 8\. The substance responsible for primary dysmenorrhea is: **Prostaglandins**