N715 Exam 3 Pt 3 PDF

The basement membrane, the endothelial lining with the innate immune response processes Mesangial cells that help regulate sodium but also protect the kidneys from allowing toxic substances to damage the basement membrane and get it through the nephrons themselves Glomerular filtrate: plasma...

The basement membrane, the endothelial lining with the innate immune response processes Mesangial cells that help regulate sodium but also protect the kidneys from allowing toxic substances to damage the basement membrane and get it through the nephrons themselves Glomerular filtrate: plasma – the plasma proteins (albumin), so the large albumin molecules stay within circulation, but everything else in circulation is going to get passed through the glomerulus so that we can regulate fluid/water content but also the balance of electrolytes. Glomerulus and basement membrane are crucial to maintaining overall homeostasis and life. On the far right: Glomerular capsule enters the nephrons and some of the nephrons are a little bit shorter (they are isolated to the outer aspect of the kidney, the renal cortex). Other nephrons extend more deeply. Bigger and longer nephrons= more surface area for reabsorption of sodium chloride and water and those extend down into the renal medulla. After passing through the various nephrons, the final glomerular filtrate, which will become urine, passes through into collecting ducts which then form the renal pelvis and enter into the ureter for storage in the bladder and elimination. Wrapped all around these nephrons is the juxtaglomerular apparatus that allows blood flow that produces glomerular filtrate in that little ball of arterioles that enters into the Bowman’s capsule and also carries away fluid that has been filtered or the substances that have been filtered that are going to go back into the vascular space. Ultimately resulting in the byproduct of urine.  Close up of the renal corpuscle underlying there along the interior aspect the basement membrane, the meningeal cells that help in regulation and protection of the basement membrane and it all filters through the proximal tubule leading into the loop of henle and the nephrons there ➔ As the glomerular filtration moves through the loop of henle, its important to think where different drugs act upon the nephron. ➔ As the filtrate enters the nephron in the descending loop of henle, we see rapid reabsorption of water. \ ◆ This causes filtrate to increase in osmolality. It goes from being very dilute to very thick. ◆ A maximum glomerular filtrate to osmolality of 1200 millimoles. ◆ At this point, selective reabsorption of sodium chloride and filtration occurs and the osmolality goes back down. Elimination of byproduct of urine is seen. Approach to Kidney Injury  What causes AKI? Is it not getting adequate perfusion to maintain function of the cells? Is it something going on within the kidney or intrinsic issues like glomerulonephritis, inflammation of the glomerulus itself? Is it infectious or autoimmune? What is it doing that is causing inflammation and then cellular injury to the actual kidney itself, whether that’s the glomerulus, the tubule, or the cells, the space in between the cells (interstitial space) and the structure of the kidney tissue or is it vasculature. Is there something wrong with the vessels supplying the nephrons themselves (vasculitis, an inflammation of the vascular structures?) Do we have malignant or rapidly uncontrolled hypertension that is pounding against basement membrane and is going to increase permeability and allow those large molecules, the plasma proteins to slip through? When there is damage to the tubules and intersition is it causing or a result of ischemia? And those tubules are becoming necrotic because they haven’t had perfusion. Is it because of sepsis or infection or is it because there is some type of nephrotoxin whether it is a drug or a chemical. Whether that’s a process that has been toxic to the renal tubules and the interstition themselves that is the underlying cause of kidney injury. And now those nephrons are not functioning/filtering appropriately and the kidney itself is not creating or maintaining that balance of fluid and electrolytes in the body.  UPJ: where the ureter exits from the renal pelvis UVJ: is bladder, the stone is at the ureterovesical junction and its just about to pop into the bladder Pelvic brim: blood vessels that cross over the border, and if there’s mention of that, then that can mean that there’s some type of vascular compromise as something travels down the ureter Pre-renal, Intrinsic, Post-Renal, Prerenal: are there pathologic conditions that are preventing good perfusion to the kidneys so that they can function? ○ Prerenal kidney issues result from decreased blood flow to the kidneys without direct kidney tissue damage. They’re often due to factors outside the kidney that reduce blood perfusion, like dehydration, blood loss, low cardiac output, or systemic vasodilation (e.g., septic shock) ○ Reduced renal perfusion causes a drop in glomerular filtration rate (GFR). ○ The kidneys attempt to compensate by reabsorbing sodium and water, which can lead to highly concentrated urine. ○ Urine tends to have a low sodium concentration (20:1 in prerenal cases. Intrinsic: ○ Intrinsic kidney issues involve direct damage to the kidney tissue. Common causes include acute tubular necrosis (ATN),  glomerulonephritis, or interstitial nephritis, often due to nephrotoxic agents (e.g., certain antibiotics or NSAIDs), prolonged ischemia, or autoimmune conditions. ○ Damage to the kidney's structures (glomeruli, tubules, or interstitium) disrupts normal function. ○ ATN is the most common cause and results from cell injury within the renal tubules, which compromises filtration and reabsorption. ○ Urine analysis often shows muddy brown casts (in ATN) or cellular casts (in glomerulonephritis). The BUN/Creatinine ratio is typically closer to 10:1. Post-renal: Some type of obstruction/ blockage that is causing back up of urine that the kidneys have produced back up into the renal callouses and that increase in pressure and the increasing volume and congestion is going to cause cellular injury and damage itself and we see a rise in creatine ○ Postrenal kidney issues stem from obstruction in the urinary tract, which prevents urine outflow. ○ Common causes include kidney stones, tumors, prostatic hypertrophy, or strictures. ○ Obstruction increases pressure within the renal tubules, which impedes filtration and can lead to hydronephrosis (swelling of the kidneys due to urine buildup). ○ Persistent obstruction may cause structural kidney damage if not relieved. ○ Initial lab findings may show variable sodium and osmolality levels, but obstruction can lead to intrinsic damage over time. If someone has a rising creatinine = decreasing renal function. Creatinine is a protein that is a product of breakdown of muscle. We are constantly generating creatinine but we should be eliminating it almost completely by the kidneys that is why our normal serum creatinine should be < 1 (0.9, 0.8 etc) because we should be eliminating all the creatinine that is being generated through the urine. BUN: is the breakdown of proteins and not specific to muscle (nonspecific). If we are dehydrated there will be a increase in BUN but we will be excreting the normal amount of creatine and if we have healthy kidneys so we’ll see an increase BUN to creatinine ratio BUN to creatinine ration is valuable. Should be a ratio of 10:20-1. if that goes up, if we have a normal creatinine of 0 and the BUN has gone up to 30 then that person is very dehydrated (pre-renal cause, something is going on before it gets to the kidneys)  If something is post-renal and something is backing up, then we can’t eliminate any by products of protein breakdown and more specifically that includes the breakdown of muscle or creatinine. Both the Bun and creatinine is going to be elevated in post-renal conditions. If its intrinsic, ratio will be around 10:1 because kidneys themselves are causing some damage to the basement membrane and therefore cannot effectively eliminate creatinine. So ration 10-1, low side to a BUN /creatinine ratio Starvation/ liver disease: unable to process proteins and break them down and we can actually see a decrease BUN because we can't process proteins at all and yet we’re eliminated the breakdown of muscle so we’ll have normal creatinine and that would indicate some kind of starvation state Aging and Renal Function By our 40’s we lose approximately 10% of renal function with each decade We’re losing the actual number of glomeruli that is functional and are present in the kidneys→ They tend to hypertrophy meaning there’s relaxation of the basement membrane and there are changes in the foot processes in the podocytes which help protect the glomeruli to help them to function. Tubules tend to atrophy and we lose ability for collection as well as the efficiency of the loops of Henle.  We see alteration in production of energy and angiotensin ll which is a potent vasoconstrictor in the body. Different vascular regulationà we see increasing endothelial dysfunction and oxidative stress. We can see the accumulation of atherosclerotic plaque foam cell, and increased risk of platelet aggregation and clot formation which would lead to ischemia and even necrosis within the kidney We need the ability to completely filter the plasma to effectively reabsorb the correct amount of water based on the level of our antidiuretic hormone to regulate the amount of sodium, chloride, and other substances in the blood and how that closely relates to the specific gravity or osmolarity of the glomerular filtrate and as we move along the loop and produce urine. Specific gravity tells a lot about the nephron’s ability to concentrate and to effectively reabsorb water and different solutes because where salt goes, water is going to follow. Occult blood: hemolyzed? cells (RBC have broken open such as with rhabdomyolysis) WBC: leukocytes indicating infection/inflammation RBC: can indicate bleeding along the tract--> irritation from bladder infection or kidney stone scraping along ureters leading to micturition of whole RBCs Nitrite: product of gram negative bacteria Glucose: should not be leaking into  Leukocyte esterase: product of inflammation along the genitourinary lining, not very specific but indicates there’s some type of infection going on ○ WBC + Leukocyte esterase= indication of infection and if you add positive nitrites= infection from gram negative bacteria Glucose: should not be leaking into the urine. If basement membrane is damaged or very viscous or hyperosmolar glomerular filtrate (a lot of glucose in the blood) then some of that can leak through the urine and then we have glycosuria Ketones= product of muscle and fat breakdown. So if someone is in lactic acidosis and they’re breaking down fat and its also going to be present with ketone bodies that are caused by diabetic ketoacidosis Epithelial cells: should not be present. If present, person didn’t wipe well, not a clean catch Bacteria: suspicion that its dirty Blood is seen on the left, this pt has rhabdomyolysis (coca-cola colored urine), lysed RBC in there (brownish) which is the spillage of heme from hemolyzed broken RBCs On the right is bloody urine because they are intact RBCs. Something is going on in the urinary tract because there is whole RBCs (indicates bleeding). 2. Relate the clinical manifestations of renal or urinary tract disease to the clinical manifestations found on history and examination. Glomerulonephritis Classification ONSET: acute, chronic or rapidly progressing PRESENTATION: nephrotic or nephritic syndrome CAUSE: ○ Autoimmune ○ Infective ○ Genetic ○ Metabolic ○ Ischemic/Toxic Common Risk Factors Family history Autoimmune Disorders Cancer Infection Diabetes Medication Regular exposure to toxins Function of Kidneys Maintaining ACID-base balance Maintaining WATER balance ELECTROLYTE balance TOXIN removal BLOOD Pressure control Making ERYTHROPOIETIN Vitamin D metabolism Internal Structures Hilum ○ Medial indentation where renal blood vessels, nerves, lymphatic vessels and ureters enter or exit the kidney Cortex ○ Outer layer of the kidney Medulla ○ Inner portion of kidney that consists of pyramids  Pyramids ○ Project into minor and major calyces Calyces ○ Chambers that receive urine from the collecting ducts and form the entry into the renal pelvis. Renal Columns ○ Extension of cortex that extend between the pyramids to the renal pelvis Renal Pelvis ○ Extension of the upper ureter Epithelial Cells ○ Line walls of calyces, pelvis and ureter Smooth muscle cells ○ Contract to move urine to the bladder Lobe ○ Structural unit of the kidney and contains a pyramid and the overlying cortex ○ There are 14-18 lobes per kidney Renal Process: Glomerular Filtration ○ Initial process in urine production ○ Membrane is highly permeable and allows fluid and small solutes to pass to Bowman’s space. Tubular Reabsorption ○ Movement of fluid and solutes from the tubular system to the peritubular capillaries ○ Body is able to retain fluid and desired solutes Tubular Secretion ○ Movement of solutes from the peritubular capillaries into the tubular system ○ Body secretes unwanted or excess substances Excretion  ○ Removal of the end products of metabolism such as urea, creatinine, uric acid, drugs, and foreign chemicals Nephron Classification: Nephron is the functional unit of the kidney and each kidney contains about 1.2 million nephrons Composed of the renal corpuscle, proximal tubule, loops of Henle, distal tubule, and collecting tubule Two types of nephron based on location in renal parenchyma ○ Cortical- perform excretory & regulatory functions ○ Juxtamedullary- role in concentration & dilution of urine Renal Corpuscle: Small, round located in renal cortex Glomerulus: loops of capillaries that filter fluid and small molecules Bowman’s Capsule: Collects filtered fluid and solutes Renin-Angiotensin- Aldosterone System: Kidneys senses a drop in BP and releases renin which is combined with angiotensin which is produced in the liver to produce angiotensin l. Angiotensin l is then uses an enzyme from the lungs called angiotensin converting enzyme (ACE) to create angiotensin ll. Angiotensin ll causes vasoconstriction on its own which will increase BP but is also activates aldosterone to be secreted from the adrenal cortex and aldosterone goes down into the collecting duct of the nephron and will reabsorb sodium and where sodium goes water follows do water will be reabsorbed as well. Aldosterone goes in an reabsorbs sodium and kicks K+ back out into the collecting duct and the water will follow and be reabsorbed as well. If there’s less water in the collecting duct, there’s going to be a decrease in urinary flow. ◾ Glomerulonephritis Patho: Inflammatory response in the glomerulus that causes damage to the glomerular capillaries IgA nephropathy is the most common cause of glomerulonephritis worldwide  Clinical Manifestations: Porous basement membrane leads to: Azotemia-buildup of waste products in blood ○ BUN > 21 mg/dL ○ Increased Cr Proteinuria Hematuria RBC casts (aggregate RBCs) Results in a decrease in GFR ○ Activates RAAS ○ Increased reabsorption of sodium ○ Water retention Increase in RAAS: ○ Oliguria ○ Hypertension: headache ○ Edema Periorbital edema Peripheral edema Pulmonary edema Crackles, SOB ○  ○ Progression of Disease/ Prolonged inflammatory response leads to: ○ Glomerular sclerosis ○ Interstitial Fibrosis ○ Progresses to: CKD ESRD Nephritic Syndrome ○ Loss of epithelial cells and basement membrane Nephrotic Syndrome ○ Loss of podocyte function Rapidly Progressive Glomerulonephritis (Crescentic Glomerulonephritis) ○ Rapid loss of renal function over a very short period (days to weeks) ○ Nephritic urine analysis ○ Renal biopsy—cellular crescent formation in the glomeruli, which is a proliferative cellular response of parietal epithelial cells within the Bowman space.  Goodpasture Syndrome: ○ Type II hypersensitivity reaction against the basement membrane in the lungs and kidneys ○ Circulating auto-antibodies attach to glomerular basement membrane→activate complement cascade→tissue injury ○ Environmental or infectious triggers interacting with genetic predisposition ○ Associated with Nephritic syndrome Nephrolithiasis: kidney stones/renal calculi Risk Factors (Genetic, Systemic, Metabolic, Environmental) ○ Warm climates, high humidity, summer months, global warming ○ Decreased fluid intake ○ Family History ○ Diet high in purines (beer and meat) and sodium – DASH or Low oxalate diet suggested ○ Decreased calcium intake ○ Diabetes ○ Obesity ○ Hypertension ○ Atherosclerosis ○ Metabolic syndrome ○ UTI ○ Urinary stasis (BPH, neurogenic bladder, ureter strictures) ○ Hyperparathyroidism (reduced bone mineral density) ○ Gouty arthritis ○ Cystinuria and Xanthinuria (genetic disorders) ○ Adenine Phosphoribosyltransferase deficiency ○ Dent's disease ○ Medications – topiramate, zonisamide Pathophysiology ○ Kidney stone formation typically requires a nucleus that can form a substrate for crystal growth in supersaturated urine. Injured epithelial cells, bacteria, and Randall’s plaques can serve as nuclei. Genetics, anatomical abnormalities, urinary stasis, inflammation and other diseases can also increase the risk of nephrolithiasis. ○ Randall’s Plaques  calcium phosphate deposits in the basement membrane of the thin limbs of the loop of Henle. Progressive enlargement of these deposits rupture through the epithelium over the renal papillae and into the calyces, where calcium phosphate or calcium oxalate can grow and aggregate into nephrolithiasis. ○ Genetics: Heritable monogenic causes of kidney stones include cystinuria, Dent’s disease, primary hyperoxaluria, and adenine phosphoribosyltransferase deficiency. ○ Anatomic Abnormalities such as medullary sponge disease, polycystic kidney disease and urothelial diverticula are associated with increased risk of nephrolithiasis. ○ Urinary Stasis from the above abnormalities is likely a major mechanism of lithogenesis ○ Inflammation: Studies suggest that inflammation plays a role in stone formation. ○ Autoimmune Diseases and Other Chronic Conditions such as Sjogren’s syndrome, cystic fibrosis, metabolic syndrome, and celiac or Crohn’s disease can increase predisposition to kidney stones. ○ Renal stone formation is related to several complex factors related to: o Supersaturation Supersaturation refers to a state in which solutes in a solution are present at concentrations that exceed their solubility and thus are more likely to form precipitate if the urine is stagnant Supersaturation with stone-forming salts leading to precipitation, such as calcium oxalate and magnesium ammonium phosphate o Precipitation Urine is comprised of several different cations and anions capable of binding together to form precipitate or salts o Crystallization or aggregation Describes the process by which crystals grow starting from a small nucleus to a larger stone Nucleus can be precipitate, Randall's plaque, or injured epithelium Theory proposed of "free-particle mechanism" and "fixed particle mechanism" to describe crystal formation  o Effect of stone inhibitors There are several mechanisms that prevent stone formation including the presence of citrate, uromodulin, pyrophosphate, and magnesium, but can be overwhelmed with supersaturation o Urine pH Low or high pH affects solubility of different solutes, thus different types of crystals form at different urine pH ○ Types of Stones: ○ Calcium Stones Most common type of kidney stone Calcium Oxalate and Calcium Phosphate are most common types Hypercalciuria (elevated levels of calcium in urine) most common abnormality leading to calcium-containing stones Often related to combination of low urine volume, hypercalciuria, hypocitraturia, hyperoxaluria, and hyperuricosuria that creates environment that promotes formation of stones Hypothesized calcium stones form around Randall's plaques ○ Uric Acid Stones o Occur in patients that excrete excessive uric acid in the urine o Often formed in conditions with low urine pH, low urine volume, and hyperuricosuria o Uric acid is less soluble at a lower pH, making thus more likely to form precipitate in acidic urine o Uric acid is byproduct of purine metabolism, which occurs with diet high in animal protein and other foods ○ Struvite Stones: Magnesium Ammonium Phosphate or Calcium Carbonate-Apatite Can fill entire renal pelvis and form staghorn calculus Formed in patients with chronic UTI's with presence of urease producing organisms (Klebsiella, proteus, E. Coli) Certain bacteria and yeast produce the enzyme urease that breaks down urea, a compound found naturally in urine, into ammonium and bicarbonate, which can increase the urine pH and thus lower solubility Signs and symptoms: ○ 40% of patients with kidney stones are asymptomatic ○ Pain ▪ Often occurs when stone enters or obstructs the ureter and correlates to location of stone in urinary tract  ▪ Can have a sudden-onset of abdominal pain that is cramping in nature, associated with moderate to severe colic and mainly localized to flank or anterior lower abdomen ○ Hematuria ▪ Related to damage to epithelium from stone irregular shape and size ○ Nausea and vomiting ▪ Related to shared splanchnic innervation of the kidneys and intestines ○ Dysuria ○ Urgency Complications: ○ Hydronephrosis ○ Acute kidney injury ○ Sepsis from infected stone and/or UTI 3. Assimilate the phases of infection in the female reproductive system with long term complications if left untreated; especially sexually transmitted infections APPLICATION HOURS -- GENITOURINARY OBJECTIVES Concept of Ascending Infection ○ E.g. Biliary colic gallstones -> cholecystitis -> can become ascending cholangitis -> become septic Pelvic Inflammatory Disease Pre-intrinsic-post renal etiology Fxn of glomerulus and nephron ○ Basement membrane of glomerulus -- can assess for problems w/ kidneys Landmarks of urinary & genital systems Notes **Glomerulonephritis = INTRINSIC (within the kidney itself) Kidney Stones ○ Hydronephrosis see hydronephrosis and s/s Key markers in Lab Studies BUN: represents breakdown of protein (waste product) ○ E.g. azotemia - products of protein in blood dt not processing/breakdown proteins -> elevated BUN  Creatinine (waste product): typically a low number since we primarily should be clearing all of it from the kidneys , ratio is 1 or below PID Key Points NP Practice Clinical Signs on Exam ○ Abscess - tubalovarian abscess - can be fatal ○ Salpingitis- along fallopian tube- pus goes into peritoneum -> peritonitis - disseminated infection ○ SIGNS OF PID Painful when walking/movement, fever, dyspareunia, quick onset Checking cervical motion tenderness -> see jumping dt pain Patho ○ Gonorrhea and Chlamydia* #1 cause of PID - invade epithelial, destroy cilia, uterus along the tubes and cause permanent scarring -> inc risk infertility + ectopic pregnancy & uterine cancer ○ Vaginitis & Cervicitis = lower reproductive infections ○ PID Upper reproductive system: ABOVE the cervix, uterus, fallopian tubes w/ salpingitis & ovaries-oophoritis Pyelonephritis bacteria = ANAEROBIC; usually multiple organisms/flora Although STIs can commonly cause PID, it can happen in late stages during menstrual period 2 EXEMPLARS Glomerulonephritis ○ Leaking of protein & RBCs (casts w/ nephritic) from broken basement membrane ○ With more inflammation, worsens the leakage process ○ Reversible ○ Salt reuptake from collecting duct, water follows-> edema ○ After RAAS removing water from collecting ducts - less urine, filtrate remaining RAAS activated due to dec. filtration and compromise; see prerenal conditions (think body is having hypotension and lack of perfusion) Edema formation ○ Infection of glomerulus and effect on basement membrane Swelling, more space, so more proteins spill in case of nephrotic system; change in polarity - losing negative charge and dec regulation of proteins going out spilling into the urine [inc. proteinuria w/ nephrotic syndrome] Nephrotic = overall pouring out; losing negative charge Nephritic syndrome = inflammatory ○ Primary: antibodies attacking kidney directly ○ Secondary: external process causing condition to happen ○ **If Goodpasture’s Syndrome is example of Type II Hypersensitivity reaction [Antibodies attacking specific tissue - epithelia of basement membrane; cytotoxic; specific antibody] ○ **Why is post-streptococcal GN a type 3 hypersensitivity reaction? Not seen as often Antigen/antibody complexes are circulated in the blood and get caught in the glomerulus damaging to the tissue  Predisposing factors: autoimmune conditions; Berger’s disease, HTN, drugs, vasculitis Mesangial cells play huge role in Concentration of glomerular filtrate through basement membrane Nephrolithiasis - Kidney Stone ○ Kidney stones - high calcium can be predisposing factor ○ Symptoms: cold diaphoresis, tachypnic, colic/cramping pain ○ Leakage of blood / hematuria; pt so uncomfortable keeling over & vomiting dt massive inflammatory response w/ stone traveling -> they’re fine once stone passed through uretovesicular junction [UVJ] to bladder -> symptoms relieved If stone at the UPJ, still has a ways to go! ○ *High purines (beef/red/organ meats, cheese, beer, aged foods, etc.) diet more predictive of stone formation ○ *CALCIUM OXIDE is most common ○ *Stones migration down ureter into the bladder and pain associated Calcium Oxide - most common Uric Acid- pts with gout will get these Struvite associated w/ bacteria; frequent/chronic UTIs “Spiky” and stick along the ureters as it travels ○ Predisposing Factors Dehydration and being out in the heat, summer months Occupations: outdoor construction, landscapers ○ Bleeding along epithelial lining of ureter as stone scrapes down -> whole blood cells in urine of UA Heme is lysed RBCs - rhabdomyolysis - in urine w/ UA ○ Plasma protein systems -- KININ dt vasodilation cramping pain & synthesis and activation of prostaglandins Why toradol works better than opioids to target prostaglandins ○ SIZE MATTERS (~5 mm diameter see hydronephrosis, backup, kidney making urine that cannot escape - urine backup into calluses & medulla) ○ Urologic emergency: uti (fever, infection) and kidney stone occuring at same time ○ ○ Week 12 - Endocrine ENDOCRINE OVERVIEW Endocrine System Functions Differentiation of reproductive and central nervous systems in the developing fetus​ Stimulation of sequential growth and development​ Coordination of male and female reproductive systems​​ Maintenance of an optimal internal environment​​ Initiation of corrective and adaptive responses when emergency demands occur Cellular Signaling  Endocrine Paracrine Autocrine NEGATIVE FEEDBACK LOOPS HYPOTHALAMIC-PITUITARY AXIS [HPA] POSITIVE FEEDBACK LOOP HORMONE TRANSPORT Release into circulatory system by glands and distributed throughout the body Water soluble hormones  ○ Circulate free, unbound forms ○ Large molecules, diffuse poorly ○ Rapid action, short duration Lipid soluble hormones ○ Synthesized from cholesterol Androgens, estrogens, glucocorticoids Mineralocorticoids, Vit D ○ Primarily bound Carrier or transport protein Hormone Receptors Target cells​ Recognize and bind with a high affinity to hormones​ Initiate a signal​ The more receptors, the more sensitive the cell​ Up-regulation​ Low concentrations of hormones increase the number of receptors per cell.​ Down-regulation​ High concentrations of hormones decrease the number of receptors. Plasma Membrane Receptors and Signal Transduction -- Hormone binding Lipid soluble goes right through Water soluble binds to receptor -- G-coupled protein -> second messenger to ultimately get cellular response First messenger hormone -> G-coupled proteins – generate ATP & cyclic AMP to act as second messenger to cause specific target cell alteration in function Hormone Effects Three routes stimulate hormone effects​ 1. Acting on preexisting channel-forming proteins to alter membrane channel permeability​ 2. Activating preexisting proteins through a second messenger system​ 3. Activating genes to cause protein synthesis​ Two general effects​ 1. Direct​- Obvious immediate effects on cell function​(Ex. Thyroid hormone increases cellular metabolism)​ 2. Permissive​- Subtle effects, dose dependent​(Ex. ADH at low levels causes Na, H2O retention high levels vasoconstriction) Trophic hormones from hypothalamus​ Prolactin-inhibiting​ Thyrotropin-release: dictate what hormones release from pituitary gland​ >>somatostatin – regulate blood flow to gut​ >>Growth hormone​ >>Gonadotropin-releasing factor ​ >>corticotropin-releasing hormone – production cortisol & ACTH​ >>Substance P​ Anterior pituitary: Adenohypophysis ​ Posterior pituitary: Neurohypophysis Hormones of the Anterior Pituitary Corticotropin-relate Glycoproteins Somato-mammotro Minor Corticotropin d Hormones pin Adrenocorticotropic Thyroid-stimulating Growth hormone B-lipotropin- fat hormone (ACTH) hormone (TSH) (GH) catabolism Follicle-stimulating hormone (FSH) Melanocyte-stimulat Luteinizing Prolactin B-Endorphins- pain ing hormone (MSH) hormone (LH) perception