Renal Physiology Remediation Exam 2 PDF

RENAL PHYSIOLOGY -- LECTURES 33-45 ================================== **[Lecture 33 - Distribution and Measurement of Fluid Volumes]** - List the varying compartments of fluid distribution and accompanying spaces connecting them. - 60% of total body weight is water - 40% of...

RENAL PHYSIOLOGY -- LECTURES 33-45 ================================== **[Lecture 33 - Distribution and Measurement of Fluid Volumes]** - List the varying compartments of fluid distribution and accompanying spaces connecting them. - 60% of total body weight is water - 40% of total body weight is Intracellular Fluid - 20% of total body weight is Extracellular Fluid - 15% is Interstitial Fluid - 5% is Plasma - Intracellular Fluid Cell Membrane Interstitial Fluid Capillary Membrane Plasma - Understand the properties of substances that are used to measure extracellular fluid volume. - V = amount/concentration - 1ml of a 1,000 mg/ml solution and final concentration of 0.3mg/ml - V = (1ml\*1,000 mg/ml)/0.3mg/ml - V = 3,000 ml - Albumin is an anion that does not cross capillaries and should not be in the urine - Mannitol can cross capillaries - Determine how SIADH impacts body fluid distribution. - In SIADH, water is added to both the ECF and ICF, resulting in a decrease in osmolarity (keeps free water). - This is a hypoosmotic situation in which there is volume expansion (water is gained). **[Lecture 34 - Principles and Overview of Renal Function]** - List and compare the competing Starling forces that control fluid movement across a capillary wall. - Hydrostatic pressure is what primarily causes water and solutes to be pushed out of the plasma and into urine. - Dialysis is driven by a hydrostatic pressure gradient. - There is no capillary osmotic pressure in a healthy Bowman's capsule due to the lack of albumins - Determine how plasma volume impacts RAAS activity. - Renin secretion can be stimulated by decrease blood pressure, decreased sodium delivery in the Macula Densa, increased sympathetic tone - Low blood volume that results in low blood pressure will activate RAAS - Renin is released by the kidney and converts Angiotensinogen to Angiotensin I - ACE is released by the lungs and converts Angiotensin I to Angiotensin II - Activation of RAAS leads to - Kidney -- Constriction of the glomerular efferent arteriole and an increase in Na^+^/H^+^ exchanger activity - Posterior Pituitary -- ADH secretion (Reabsorption of free water and urea) - Vascular Smooth Muscle -- Hypotension - Hypothalamus -- Stimulates thirst - Adrenal Cortex -- Aldosterone secretion (Increase Na reabsorption) **[\ ]** **[Lecture 35 - Renal Blood Flow and Glomerular Filtration Rate I]** - List how constriction of the afferent arteriole effect glomerular hemodynamics. - Constriction of the Afferent Arteriole decreases both RPF and GFR. There is no change in the FF due to a drop in both RPF and GFR. - List how changes in glomerular capillary pressure impact GFR (Glomerular Filtration Rate), RBF (Renal Blow Flow) and FF (Filtration Fraction). - A list of medical terminology Description automatically generated with medium confidence - Recall Starling forces in the kidney and how they impact net filtration pressure. - Net Filtration Pressure = Glomerular Hydrostatic Pressure -- Bowman's Capsule Pressure (Hydrostatic) - Glomerular Oncotic Pressure - 10 mmHg = 60 mmHg -- 18 mmHg -- 32 mmHg - Glomerular Hydrostatic Pressure - Glomerular Oncotic Pressure - Bowman's Space Hydrostatic Pressure - Bowman's Space Oncotic Pressure **[Lecture 36 - Renal Blood Flow and Glomerular Filtration Rate II]** - Understand renal handling of creatinine. - GRF = (creatinine in urine x flow volume) / creatinine in blood - GFR = (125 mg/ml x 1ml/min) / 1mg/ml - GFR = 125 ml/min - Creatinine is higher in urine than the blood - Creatinine is endogenous - Predict the effects of change in tone of the afferent or efferent arteriole on GFR, RBF, and FF. -  - Determine the handling of a substance by comparing its clearance to that of inulin. - GRF = (Inulin in urine x flow volume) / inulin in blood - Inulin is the best way to determine GFR and is not endogenous - It is filtered at approximately 100% at the glomerulus **[\ ]** **[Lecture 37 - Reabsorption and Secretion I]** - List the primary substances that are reabsorbed in the proximal tubule. - Na^+^, Mg^2+^ - Na^+^ with Cl^-^, Ca^2+^, PO~4~^3-^ - 85-90% of bicarbonate (HCO~3~^-^) in the form of CO~2~ and water on the apical side - Amino acids, glucose (SGLT2 in early PCT, SGLT1 in late PCT) - Water and urea passively - List the transporters in the proximal tubule involved in the physiologic response to reduced extravascular volume. - Per Chat GPT - In the context of reduced extravascular volume, the kidney activates several mechanisms to conserve sodium, water, and other vital solutes: - Enhanced sodium reabsorption through NHE3, SGLT2, and NaPi transporters. - Increased water reabsorption via aquaporins (AQP1). - Modulation of acid-base balance via bicarbonate transporters (NBCe1, NHE3). - Optimized solute transport via Na+/K+ ATPase pumps to establish gradients for sodium reabsorption. - These transporters are critical in the proximal tubule\'s adaptive response to conserve sodium and water during volume depletion and contribute to the maintenance of extracellular fluid volume and blood pressure. - Understand that when plasma glucose is above the transport maximum (Tm) of the renal glucose transporters that excess glucose is not reabsorbed and is excreted into the urine. - Some nephrons may become saturated at 350 mg/min, while others may be able to keep up at levels of 400 mg/min. Average is considered 375 mg/min. **[Lecture 38 - Reabsorption and Secretion II]** - Recognize that albumin, immunoglobulins, and some medications are reabsorbed by endocytosis, a completely different mechanism than channels or transporters. - Proteins, such as albumin, and peptide hormones, such as insulin, are reabsorbed by endocytosis and later converted to free amino acids. - List renal transporters and determine what type of transport they provide. - Secondary - Cotransport with Na^+^. - Glucose, amino acid, phosphate, lactate, citrate. - Countertransport - Na^+^/H^+^ - Hydrogen into the lumen to combine with bicarbonate (HCO~3~^-^) to form of CO~2~ and water - Recognize splay and recall why it occurs. - Splay phenomenon is due to variability in saturation thresholds amongst different nephrons. - Some nephrons may become saturated at 350 mg/min, while others may be able to keep up at levels of 400 mg/min. **[\ ]** **[Lecture 39 - Sodium Balance I]** - List the segments of the nephron and how potassium is handled in each. - K^+^ - Reabsorption - 67% in the proximal convoluted tubule - 20% in the thick ascending limb - Na^+^/K^+^ (3/2) is used in the early PCT to reabsorb Na^+^. Potassium is transported into the cells. - NKCC (Na-K-2Cl) symporter is in the Thick Ascending Limb - Na^+^, excretion is about 100 mmol/day, reabsorption: - 67% in the proximal convoluted tubule - 25% in the thick ascending limb - 5% in the distal convoluted tubule - 3% in the inner medullary collecting duct - Determine which segment of the nephron does not require energy to reabsorb water. - Water Reabsorption is passive - 67% in the proximal convoluted tubule - 15% in the loop of Henle - 0% in the early distal convoluted tubule - 8-17% in the late distal tubule and collecting duct - List the physiological effects of mineralocorticoid blockade. - Aldosterone's major site of function is the late DCT and cortical collecting duct - Aldosterone increases K^+^ secretion and increases Na^+^ reabsorption. - Blocking aldosterone results in decreased K^+^ secretion and decreased Na^+^ reabsorption. - This results in natriuresis and hyperkalemia. - This results in decreased blood pressure and hypovolemia. **[Lecture 40 - Sodium Balance II]** - Understand that the Na/K ATPase creates an electrochemical gradient to allow for transport the epithelial cell. - Na^+^/K^+^ (3/2) is used in the early PCT to reabsorb Na^+^. Potassium is transported into the cells. - Name the terminal site of sodium reabsorption of the nephron. - 3% is reabsorbed in the inner medullary collecting duct - List the mechanisms of potassium-sparring diuretics. - Spironolactone, a steroid and aldosterone-antagonist, prevents aldosterone from entering the nucleus of the principal cells and therefore blocks the synthesis of mRNAs and new proteins. - Amiloride and triamterene bind to the luminal membrane Na+ channels and inhibit the aldosterone-induced increase in Na+ reabsorption. - The K+-sparing diuretics produce only mild diuresis because they inhibit such a small percentage of the total Na+ reabsorption. However, as the name suggests, their main use is in combination with other diuretics to inhibit K+ secretion by the principal cells, as discussed in the section on K+ handling. **[\ ]** **[Lecture 41 - Potassium, Phosphate and Calcium Balance ]** - List the effect that phosphate has on PTH secretion and the impact that PTH has on renal phosphate handling. - Parathyroid hormone (PTH) regulates the reabsorption of phosphate in the proximal tubule by inhibiting Na^+^-phosphate cotransport, thereby decreasing the Tm for phosphate reabsorption. When PTH inhibits phosphate reabsorption, it causes phosphaturia, or increased phosphate excretion. - Little to no reabsorption occurs beyond the proximal tubule. - Understand how excess parathyroid hormone will impact renal calcium and phosphorous. - PTH decreases phosphate reabsorption in the proximal tubule, leading to excretion. - PTH increases Ca^2+^ reabsorption in the distal tubule - Recall the physiologic effects of calcitriol. - Calcitriol is a hormone (Vitamin D3 hormone). - In the proximal tubule of the kidney, PTH creates the active form. - Calcitriol is one of the hormones that controls Ca^2+^. - Calcitriol leads to decreased Ca^2+^ and phosphate excretion in the kidney and increased Ca^2+^ and phosphate release in the bones. - AKA Calcitriol allows for calcium to be reabsorbed in the kidney **[Lecture 42 - Acid Base Chemistry]** - Describe the variables of the Henderson-Hasselbalch equation. *(Listed twice)* **Variable** **Definition** **Example in Physiology** -------------- ------------------------------------------------------- ------------------------------------------------- **pH** Measure of hydrogen ion concentration (acidity). Blood pH (\~7.4) **pKₐ** The pH at which a weak acid is 50% dissociated. pKₐ of carbonic acid is 6.1 in blood buffering. **\[A⁻\]** Concentration of the conjugate base (the anion form). Bicarbonate ions (HCO₃⁻) in blood. **\[HA\]** Concentration of the weak acid (proton donor). Carbonic acid (H₂CO₃) in blood. - Respiratory Alkalosis - Can be caused by hyperventilation - Increased pH due to decrease in CO~2~ - Respiratory Acidosis - Can be caused by shallow breathing - Decreased pH due to increase in CO~2~ - Metabolic Alkalosis - Increased pH due to increase in HCO~3~^-^ - Metabolic Acidosis - Decreased pH due to decrease in HCO~3~^-^ **[Lecture 43 - Water Balance]** - List serum and urine osmolality values expected in diabetes insipidus. - With diabetes insipidus, there is an inability to concentrate urine. - List how ADH is regulated by hyperosmolarity and hypotension. - ADH release is increased with increased osmoreceptor firing, which is due to elevated plasma osmolality. - ADH release is decreased with increased baroreceptor firing, which is due to low blood pressure. - Recall the renal site of action of anti-diuretic hormone. - ADH increases the permeability of the collecting ducts to water (increases urea reabsorption) **[\ ]** **[Lecture 44 - Acid-Base I ]** - Determine acid base status of blood and list causes of high anion gap acidosis. - The mnemonic \"MUDPILES\" is often used to remember the common causes of high anion gap acidosis: - M - Methanol poisoning - U - Uremia (renal failure) - D - Diabetic ketoacidosis (DKA) - P - Paraldehyde poisoning - I - Infection (sepsis) - L - Lactic acidosis - E - Ethylene glycol poisoning - S - Salicylate toxicity (e.g., aspirin overdose) - Recognize that high plasma glucose will lead to production of ketoacids, thereby causing an increased anion gap. - Diabetic Ketoacidosis - Define anion gap and determine how decreased tissue blood flow may cause increased anion gap acidosis. - Anion Gap = Na^+^ - (Cl^-^ + HCO~3~^-^) - Lactic acidosis is the most common cause of increased anion gap metabolic acidosis **[Lecture 45 - Acid-Base II ]** - Recognize that proteins can present as a cation, and that excess unmeasured cations also contribute to low anion gap acidosis. - Normal anion gap is 12 ± 2 - Examples of unmeasured cations include IgG, K^+^, Mg^2+^, and Ca^2+^ - Understand that unmeasured osmols, such as ethylene glycol can present early on with elevated osmolar gap. - Determine that chronic use of diuretics leads to the development of metabolic alkalosis and that the respiratory system compensates for this. GI PHYSIOLOGY -- LECTURES 46-51 =============================== **[Lecture 46 - GI Structure & Function]** - Differentiate importance of sympathetic and enteric nervous systems in digestive function. *(Listed twice)* - SNS -- Decreases digestive processes due to fight and flight, has a net inhibitory effect (indirectly by vasoconstriction); (Secretions and sensory) - ENS -- Direct all contractile, secretory, and endocrine GI functions in the absence of extrinsic innervation. Referred to as the second brain. - Myenteric (Auerbach) -- rhythmic contractions, gut motility - Submucosal (Meissner) - secretions and sensory function - Distinguish regional innervation of the esophagus. - Vagus nerve (CN X) innervates the upper GI tract, including the striated muscle of the upper third of the esophagus; parasympathetic - Sympathetic innervation of the proximal esophagus is derived primarily from the cervical and upper thoracic paravertebral ganglia, whereas the lower esophageal sphincter is derived from the celiac ganglion **[Lecture 47 - GI Motility]** - Recognize dysphagia and recall regulatory mechanisms of lower esophageal sphincter opening. - Dysphagia -- Difficulty swallowing - Innervation of the lower esophageal sphincter is derived from the celiac ganglion - Esophageal Spasms -- Esophageal body is primarily involved - Diffuse -- contractions are uncoordinated - Nutcracker -- amplitude is excessive - Achalasia -- Lower esophageal sphincter and esophageal body are both involved - Failure of normal relaxation of lower esophageal sphincter associated with uncoordinated contractions of the thoracic esophagus - Treatment -- calcium channel blockers and nitrates, Myotomy (procedure to cut muscle to help with obstruction), botox - Distinguish between inhibitory and stimulatory innervations in GI motility. - SNS is inhibitory and mediated by norepinephrine - PNS is stimulatory and mediated by acetylcholine - ENS -- Direct all contractile, secretory, and endocrine GI functions in the absence of extrinsic innervation. Referred to as the second brain. - Myenteric (Auerbach) -- rhythmic contractions, gut motility - Submucosal (Meissner) - secretions and sensory function - Motor neurons in the myenteric plexus release Ach and Substance P, which cause smooth muscle contraction - Inhibitory motor neurons release vasoactive intestinal peptide (VIP) and nitric oxide (NO), which cause smooth muscle relaxation - Distinguish ionic basis of slow wave potentials in GI motility. - Slow waves originate in the Interstitial Cells of Cajal (ICC), which is the pacemaker - ICC membrane depolarization is due to Ca^2+^ influx and is up to 10K times higher than extracellularly - Repolarization is due to K^+^ channels opening and efflux **[\ ]** **[Lecture 48 - GI Salivary and Gastric Secretions]** - Determine likely cause of GI symptoms and role of somatostatin in alleviation of those symptoms. - Somatostatin is inhibitory and produced from the D cells regulation of gastrin secretion (inhibits acid) - Inhibits parietal cells, histamine, and gastrin - Peptic ulcers -- over acidity in the stomach - Achlorhydria -- autoimmune condition of parietal cells resulting in decreased acid production - Predict effect of vagus associated compounds on gastrin release. - Gastrin is from the G cells - Vagus nerve gastrin-releasing peptide (GRP) / bombesin G cells parietal cell H^+^ release and gastric mucosa growth (trophic influence) - Indirectly: Vagal stimulation also increases the release of histamine from enterochromaffin-like (ECL) cells in the stomach. Histamine, in turn, binds to H₂ receptors on parietal cells, stimulating the production of gastric acid. - Acidic environment has negative feedback on G-cell release of gastrin. - Somatostatin inhibits G cell gastrin secretion **[Lecture 49 - GI Accessory Secretory Organs I]** - Recall pancreatic fluid synthesis and sequence for aqueous component. - Enzymes are secreted by the acinar cells, which aqueous components are secreted by the centroacinar cells, which is then modified by ductal cells - ACh and CCK act on ductal cells - Provides rapid neutralization of acidic chyme - See PPT - Recall ionic composition of pancreatic fluid and how it is affected by flow rate. - A diagram of a fluid composition Description automatically generated **[\ ]** **[Lecture 50 - GI Accessory Secretory Organs II]** - Understand the bilirubin breakdown pathway. - Most breakdown is in the spleen, the rest in the RES, including the liver - Recognize biliary cancer symptoms and causes. - Biliary cancer (cholangiocarcinoma) is a rare but aggressive cancer of the bile ducts, and it typically presents with jaundice, abdominal pain, fatigue, and weight loss. Early detection is difficult due to the lack of specific symptoms in the early stages. Several risk factors, including chronic bile duct inflammation, PSC, cirrhosis, and parasitic infections, can increase the risk of biliary cancer. Treatment is often limited to surgical resection in early stages, with chemotherapy and palliative care options for advanced disease. **[Lecture 51 -]** **[When Things Go Wrong]** - Recall the role of the arcuate nucleus in appetite regulation and which neuropeptides are present. - The arcuate nucleus is central to appetite regulation, and its neurons are influenced by a variety of neuropeptides and hormones. NPY and AgRP promote hunger and increase food intake, while POMC, α-MSH, and CART suppress appetite. The arcuate nucleus integrates signals from peripheral hormones like leptin, insulin, and ghrelin to maintain energy homeostasis, ensuring that food intake is balanced with the body\'s energy needs. - AgRP is most potent and long lasting - Basis of IBS-D diagnostic antibody test. - Two antibodies - If either are elevated, the test is considered positive and patient can be diagnosed with IBS-D or IBS-M - Antibodies are Anti-CdtB and Anti-Vinculin - If both are not elevated, the test is considered negative [**Unknown Lecture -** **GI Digestion and Absorption**] - Distinguish between CCK, VIP and bicarbonate with respect to roles in gastric motility to determine source of symptoms/presentation. - CCK plays a critical role in regulating gastric motility by slowing gastric emptying and stimulating gallbladder contraction, leading to symptoms like nausea, bloating, and right upper quadrant pain in cases of gallbladder dysfunction. - VIP generally promotes gastric motility through smooth muscle relaxation, but an excessive VIP (as in a VIPoma) leads to watery diarrhea, hypokalemia, and achlorhydria. - Bicarbonate helps to neutralize stomach acid and protect the gastric lining. Problems with bicarbonate secretion (e.g., in conditions like pancreatitis) lead to gastritis or peptic ulcers, while excess bicarbonate can result in alkalosis and digestive discomfort. - Thus, understanding the roles of these substances allows clinicians to distinguish between different gastrointestinal conditions based on the pattern of symptoms, contributing to accurate diagnosis and treatment. ENDOCRINE AND REPRO PHYSIOLOGY -- LECTURES 52-66 ================================================ **[Lecture 52 - Principles of Endocrinology]** - Describe the four classes of hormones and how each is synthesized, stored, secreted and metabolized. - Interpret a change in a dose-response curve. - Depending on the class of hormone, predict which one will have the longest or shortest half-life. - See above table - Binding leads to a longer half life **[Lecture 53 - Hormones of the Endocrine Pancreas]** - Explain insulin's and glucagon's major metabolic actions. - High blood glucose stimulates insulin, which increase glucose uptake into the cells and converts glucose to glycogen - Insulin is essential for maintaining blood glucose homeostasis. It lowers blood glucose by facilitating its uptake into cells, promoting its storage as glycogen or fat, and inhibiting glucose production. In addition to regulating glucose, insulin also affects fat storage, protein synthesis, and electrolyte balance. - Low blood sugar stimulates glucagon, which converts glycogen to glucose - Glucagon is a critical hormone for increasing blood glucose during fasting or between meals. It does this by stimulating glycogen breakdown, glucose production, and fat breakdown. - List the physiological effects of insulin administration. - Insulin administration plays a crucial role in regulating blood glucose and supporting nutrient storage, particularly during the fed state. It promotes glucose uptake, glycogen storage, lipogenesis, and protein synthesis, while inhibiting processes like glycogen breakdown, gluconeogenesis, and lipolysis. - Increase uptake of glucose in the liver and muscles - Decrease the activity of hormone sensitive lipase - List the effects that insulin deficiency has on glucose, protein and fat metabolism. - Leads to prolonged elevation in plasma glucose due to decreased glucose uptake into the cells - Increases protein catabolism and amino acids in the blood - Increase lipolysis, leading to an increase in glycerol, fatty acids, and consequently, ketoacids **[Lecture 54 - Calcium and Phosphate Regulating Hormones]** - Describe how vitamin D3 is synthesized, stored, secreted, and regulated and explain vitamin D3's major actions. - Synthesized - First, hydroxylation occurs in the liver to lead to the formation of 25(OH)D or calcidiol. - Then, hydroxylation occurs in the kidneys and constitutes calcitriol - This is the primary regulated step - 1α-hydrolylase - Activity is increased by decreased plasma Ca^2+^, decreased plasma phosphate, and increased PTH - Stored in the liver and fat - Secreted in response to decreased plasma Ca^2+^ - Action: Stimulate Ca^2+^ and phosphate absorption in the intestines and kidneys and resorption of old bone mineralization of new bone - Diagnose a disease of calcium-sensing receptor mutation and list the expected effects on blood and urine levels of calcium and phosphate. - Familial Hypocalciuric Hypercalcemia (FHH): Caused by mutations in the CaSR (chief cells), leading to hypercalcemia, hypocalciuria, and normal or slightly elevated phosphate levels. - Increase in PTH, serum Ca^2+^, and urine phosphate - Decrease in serum phosphate and urine Ca^2+^ - Remember PTH is "Phosphate Trashing Hormone" - Know the major actions of all calcium and phosphate regulating hormones and determine the major mode of action for each. - PTH - Stimulate Ca^2+^ and phosphate absorption in the intestines and resorption of old bone, and reabsorption of only Ca^2+^ at the kidneys - Stimulated due to decreased plasma Ca^2+^ - Vitamin D - Stimulate Ca^2+^ and phosphate absorption in the intestines and kidneys and resorption of old bone mineralization of new bone - Stimulated due to decreased plasma Ca^2+^ - Calcitonin - Decreases blood calcium -- "Calci-tone-it-down"; less bone reabsorption - Stimulated due to elevated plasma Ca^2+^ **[Lecture 55 - Hypothalamic Neurohypophyseal Axis]** - Recognize the second messenger systems that are activated when ADH binds to its receptor. - V2 Receptor Activation (cAMP pathway) in the kidneys is responsible for ADH\'s primary effect of increasing water reabsorption and concentrating urine. - KIDNEYS - V1 Receptor Activation (IP3/Ca^2+^ pathway) mediates the vasoconstrictive effects of ADH, which helps regulate blood pressure by constricting blood vessels. - VASCULAR SMOOTH MUSCLE - Thus, the cAMP pathway through V2 receptors is essential for ADH\'s action on water balance, while the IP3/Ca^2+^ pathway through V1 receptors is important for the regulation of vascular tone and blood pressure. - Describe the pathologies associated with hyper- or hyposecretion of ADH and evaluate in a patient where the problem originates. - Hypersecretion of ADH (e.g., SIADH) results in water retention, hyponatremia, and hypoosmolality, with elevated urine osmolality. - Hyposecretion of ADH (e.g., diabetes insipidus) causes polyuria, polydipsia, and hypernatremia, with low urine osmolality. Depending on the etiology, it can be caused by problems with ADH production (central DI) or ADH resistance (nephrogenic DI). - Recognize the consequences of the inability to transport oxytocin and ADH and know the physiologic effects that occur with deficiencies in both. - ADH Deficiency (Diabetes Insipidus): Causes polyuria, polydipsia, hypernatremia, and dehydration due to impaired water reabsorption in the kidneys. Central DI arises from lack of ADH production, while nephrogenic DI results from kidney resistance to ADH. - Oxytocin Deficiency: Causes labor complications, failure of milk let-down, and possible social bonding issues. Oxytocin is essential for uterine contraction during childbirth and milk ejection during lactation. - Both hormones are critical for normal physiological function, and deficiencies can have a profound impact on reproductive health, fluid balance, and social and emotional well-being. **[Lecture 56 - Hypothalamic Adenohypophyseal Axis]** - Recognize how GH is regulated. - The secretion of growth hormone (GH) is tightly regulated by a variety of factors, including hypothalamic control via GHRH and somatostatin, negative feedback from IGF-1, and responses to circadian rhythms, exercise, nutritional status, and stress. - Stimulated by GHRH - Inhibited by Somatostatin and hyperglycemia - Recognize the major actions of prolactin. - Mammogenesis -- Growth and development of the mammary gland - Lactogenesis -- Initiation of lactation; increase synthesis of lactose, casein, and lipids - Define the physiological effects that occur with congenitally low growth hormone levels. - Pituitary Dwarfism - Failure to grow, but proportionate - Mild obesity - Normal IQ - Deficiency can also result in short stature and delayed puberty - NOT Laron Dwarf -- mutation in GH receptor **[Lecture 57 - Hypothalamic-Pituitary-Thyroid Axis]** - Know that propylthiouracil is a thyroid peroxidase inhibitor and list its physiologic effects. - Propylthiouracil (PTU) is an effective antithyroid drug that works by inhibiting thyroid peroxidase and reducing the synthesis of thyroid hormones (T3 and T4). It also inhibits the peripheral conversion of T4 to T3. By reducing thyroid hormone levels, PTU helps to manage hyperthyroidism and its associated symptoms such as tachycardia, weight loss, and heat intolerance. However, PTU is associated with potential adverse effects, including hepatotoxicity, agranulocytosis, and hypothyroidism, making careful monitoring necessary during treatment. - Decrease T3 and T4 formation and decrease T4 to T3 conversion - List the physiologic effects of excess thyrotropin-releasing hormone. - Excess thyrotropin-releasing hormone (TRH) can lead to hyperthyroidism due to the overproduction of TSH and thyroid hormones, resulting in a wide range of symptoms, including weight loss, heat intolerance, tachycardia, goiter, gastrointestinal disturbances, and reproductive issues like infertility. - Determine how exogenous thyroid hormone impacts the hypothalamic-pituitary-thyroid axis. - Exogenous thyroid hormone, such as levothyroxine (T4), levotriiodothyronine (T3), or combination therapies, exerts significant effects on the hypothalamic-pituitary-thyroid axis by suppressing TRH and TSH secretion through negative feedback. This suppression reduces the need for the thyroid to produce its own hormone, and when properly dosed, it helps normalize thyroid function in hypothyroid patients. However, excessive thyroid hormone replacement can suppress TSH too much, leading to potential hyperthyroidism and associated risks, requiring careful monitoring of serum TSH levels during therapy. **[Lecture 58 - Adrenal Cortex - Mineralocorticoids]** - Discuss consequences associated with hyper- or hyposecretion of mineralocorticoids. - The secretion of mineralocorticoids, particularly aldosterone, is critical for maintaining electrolyte balance, fluid volume, and blood pressure. Both hypersecretion and hyposecretion of aldosterone can lead to serious consequences: - Hypersecretion (e.g., Conn\'s syndrome) typically results in hypertension, hypokalemia, and metabolic alkalosis due to excessive sodium retention and potassium excretion. - Hyposecretion (e.g., Addison\'s disease) leads to hypotension, hyperkalemia, hyponatremia, - List the pathophysiologic effects of 21 beta-hydroxylase deficiency and determine which is most life threatening. - Increase in synthesis of adrenal androgens, precocious puberty, early appearance of secondary sex characteristics - Deficiency of cortisol -- hypoglycemia, hypotension, rapid growth, early completion short - Deficiency of aldosterone -- hypovolemia, hypotension, hyperkalemia, metabolic acidosis - List the physiologic effects of 11 beta-hydroxylase deficiency. - 11β-hydroxylase deficiency results in cortisol deficiency, mineralocorticoid excess, and androgen excess. The most prominent clinical features include virilization in females, precocious puberty in males, hypertension, hypokalemia, and metabolic alkalosis due to the accumulation of mineralocorticoid precursors like 11-deoxycorticosterone. Cortisol deficiency also increases the risk of adrenal crisis and hypoglycemia. Early diagnosis and appropriate treatment with glucocorticoids and anti-androgens are critical for managing the condition and preventing long-term complications. **[\ ]** **[Lecture 59 - Adrenal Cortex - Glucocorticoids]** - Describe actions of glucocorticoids. - Cortisol - Stimulation of gluconeogenesis - Inhibition of bone formation - Anti-inflammatory effects - Suppression of the immune response - Maintenance of vascular responses to catecholamines - CNS: decrease REM sleep, increase awake time, can cause insomnia - Predict the negative feedback effects of Cushings syndrome or Cushings disease. - In both Cushing\'s syndrome and Cushing\'s disease, the body\'s normal negative feedback mechanisms are disrupted, leading to persistently elevated cortisol levels. - In Cushing\'s disease (pituitary adenoma), the pituitary tumor produces excess ACTH, which results in high cortisol levels and impaired negative feedback. The pituitary and hypothalamus continue to secrete ACTH and CRH despite high cortisol levels. - In Cushing\'s syndrome, there is low ACTH due to adrenal tumor or excess exogenous glucocorticoids - Interpret results of the dexamethasone suppression test. **[Lecture 60 - Adrenal Medulla - Catecholamines]** - Diagnose pheochromocytoma. - Secretes hormones in bursts, so a 24-hour collection is needed. - Pheochromocytoma should be suspected in patients with episodic hypertension, palpitations, sweating, and other associated symptoms. - The most sensitive test for diagnosis is plasma free metanephrines. - Know what enzyme initiates catecholamine formation. - The initial step in catecholamine synthesis, and the rate-limiting step, is catalyzed by tyrosine hydroxylase, which converts tyrosine to L-DOPA, setting the stage for the production of dopamine, norepinephrine, and epinephrine. - Diagnose pheochromocytoma and name the initial line of therapy to control blood pressure. - Sx: adrenal mass, hot flashes, increase BP - First line treatment is phenoxybenzamine, which is an α~1~-adrenergic antagonist - Second line treatment is propranolol, a β-adrenergic antagonist **[\ ]** **[Lecture 61 - Hypothalamo-Pituitary-Gonadal Axis]** - Identify and discern how sex steroids are synthesized and regulated. - Synthesis of Sex Steroids: - Sex steroids (estrogens, androgens, and progesterone) are synthesized from cholesterol via enzymatic steps, with key enzymes such as cholesterol desmolase, 3β-HSD, 17α-hydroxylase, and aromatase playing major roles. - Regulation: - The synthesis of sex steroids is regulated by the HPG axis, where GnRH from the hypothalamus stimulates the pituitary to release LH and FSH, which in turn regulate the gonads to produce testosterone, estradiol, and progesterone. - Distinguish between primary and secondary pathologies related to hyper- and hypogonadism. - A close-up of a text Description automatically generated - Identify and discern how the sex steroids (testosterone, estrogen, progesterone) are synthesized, stored, secreted, and regulated. - Testosterone, estrogen, and progesterone are synthesized from cholesterol via enzymatic pathways involving cholesterol desmolase, 3β-HSD, 17α-hydroxylase, and aromatase. - Testosterone is primarily synthesized in the Leydig cells of the testes and adrenal glands, estradiol in the granulosa cells of the ovaries, and progesterone in the corpus luteum (ovaries). - Secretion occurs in response to GnRH, LH, and FSH secreted by the pituitary gland. - Regulation of these hormones is controlled by negative feedback loops and, in females, positive feedback during the menstrual cycle. - Their physiological effects are essential for reproduction, sexual development, and maintenance of bone and metabolic health. **[\ ]** **[Lecture 62 - Sexual Differentiation]** - Recognize general steps in sexual differentiation during embryonic development, recognize hormonal control in development of reproductive system. - Presence of the SRY gene leads to the testes - Sertoli cells produce anti-müllerian hormone - Leydig cells produce testerone - Wolfian ducts develop into male external genitalia due to testosterone - Dihydrotestoestrone leads to the devolpment of penis, scrotum, and prostate - Absence of the SRY gene leads to formation of the ovaries - Mullerian ducts develop into the fallopian tube and uterus - Determine the consequences of improper sexual differentiation and predict the outcome of the gonads, and internal and external genitalia. Predict result of abnormal hormone production during development. Determine the specific pathology associated with improper sexual differentiation given a clinical scenario. - See PPT - Determine the consequences of improper sexual differentiation and predict the outcome of the gonads, and internal and external genitalia and predict result of abnormal hormone production during development. - See PPT **[Lecture 63 - Male Reproductive Physiology]** - Recognize steps of spermatozoa production and identify storage and delivery pathways, function of glands. - Seminiferous tubules produce sperm ( rete testes efferent ducts) - Epididymis and Vas deferns serve as the storage site - Ejaculatory duct prostate gland urethra is the delivery pathway - Identify how the ANS controls erection and ejaculation. - PNS -- erection - SNS -- ejaculation - Recognize the sequence of events involved in fertilization. - Fusion of egg and sperm in ampulla of fallopian tube within 24-48 hours of ovulation - Capacitation -- Removal of cholesterol coating that surrounds sperm to enable release of acrosomal enzymes & enhanced motility - Acrosome Reaction -- Release of enzymes from acrosome break down zona pellucida and initiates cortical reaction - Block to Polyspermy -- Fast - sodium influx = temporary depolarization, prevents additional sperm from binding. Slow - calcium influx = permanent initiates cortical reaction - Cortical Reaction -- inactivation of sperm-binding receptors on zona pellucida and hardening of zona pellucida, mediated by enzymes released from egg by exocytosis. Stops sperm from advancing and additional sperm from binding  **[Lecture 64 - Female Reproduction I]** - Recognize and interpret hormonal changes during the ovarian cycles. (*Listed twice)* - - Recognize and discern steps in follicle maturation; recognize and interpret hormonal control of follicle maturation. - Follicle Development: - Follicles start as primordial follicles and go through the primary, secondary, and tertiary (antral) stages before becoming the Graafian (mature) follicle. - This process involves proliferation of granulosa cells, the formation of the antral space, and the accumulation of estrogen. - Hormonal Regulation: - FSH stimulates the growth of follicles and granulosa cell activity, leading to estrogen production. - LH contributes to the final maturation of the dominant follicle and triggers ovulation through the LH surge. - Estrogen promotes follicle growth and positive feedback for the LH surge, while also exerting negative feedbackto control hormone levels. - Inhibin and progesterone also play roles in feedback regulation. - Ovulation: The LH surge leads to the rupture of the mature follicle and the release of the oocyte. **[Lecture 65 - Female Reproduction II]** - Recognize and interpret ovarian and uterine phases/events during the ovarian & menstrual cycles. - - Recall and interpret hormonal control of mammary gland development, lactogenesis, and control of lactation. - - Lactation is inhibited in pregnancy by estrogen and progesterone - Prolactin allows for milk production - Suckling inhibits dopamine, leading to increased prolactin - Oxytocin is responsible for milk letdown (ejection) - Recognize hormonal changes that occur with menopause and discern premenopausal and postmenopausal hormone profiles. - Decrease in estradiol and progesterone - Elevated LH and FSH **[\ ]** **[Lecture 66 - Physiology of Pregnancy]** - Recall the three stages of parturition and explain how parturition is hormonally controlled. - Dilation: Contractions increase in force and number - Expulsion: Lasts about an hour and is the forcing of the fetus from mother's body - Placental: lasts about 10 minutes and is the expulsion of the placenta - Estrogen starts the weak/infrequent contractions \~30 weeks; increases oxytocin receptors - Oxytocin has a positive feedback loop to increase uterine contractions - Recognize the placenta as a transient endocrine organ and recall the hormones it can produce. - Secretes estrogens (estriol), progesterone, relaxin, hCG, placental lactogen - hCG is secreted from the trophoblasts, highest in early pregnancy - hCS is also secreted from the trophoblasts - In later pregnancy, prolactin, progesterone, and estriol are higher (in that order) - Placenta must extract DHEA-S from mother or fetus to produce androgens - Recognize events during fertilization and implantation, early embryonic development, development of placenta, including timing of specific events.