Advanced Pathophysiology Exam 4 Study Guide, Exams of Nursing

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NURS 8022 Advanced Pathophysiology Exam 4 Study Guide Exam 4 Study Guide GASTROINTESTINAL PHYSIOLOGY Anatomy of the GI system – NOT ON STUDY GUIDE • Digestive system – enteric nervous system (extrinsic and intrinsic) o Autonomic (involuntary) and hormonal control [except chewing, swallowing, defecation] ▪ Vagus nerve o Ingested substances trigger hormones that stimulate or inhibit ▪ Muscular contractions – GI motility; timely secretion of substances that aid in digestion o Located near the areas that they innervate and control • Mouth o Reservoir for chewing and mixing of food with saliva o Taste buds (chemoreceptors) and olfactory nerves are stimulated – initiates salivation and secretion of gastric juices in the stomach • Salivary glands o Submandibular, sublingual, parotid (largest; secretes saliva) o Saliva is composed of water with mucus, sodium, chloride, bicarbonate, potassium and salivary a-amylase (carb digestion) and is controlled by ANS ▪ Cholinergic parasympathetic fibers stimulate salivary glands • Ex: anticholinergic meds inhibit salivation ▪ Sympathetic beta-adrenergic stimulation decreases salivary secretion – none, little, or little with rich protein content ▪ A pH of 7.4 which neutralizes bacterial acids aiding to prevent injection ▪ Contains IgA – prevents orally ingested microorganisms • Esophagus o Conducts substances from oropharynx to stomach o Upper esophageal sphincter prevents entry of air into the esophagus during respiration o Lower esophageal sphincter (cardiac sphincter) prevents regurgitation from the stomach Increase tone by cholinergic vagal stimulation and the digestive hormone gastrin Decrease tone/relax by non-adrenergic, non-cholinergic vagal impulse and the hormones progesterone, secretin, and glucagon o Vagus nerve allows relaxation of esophagus during swallowing o Swallowing: complex event mediated by the swallowing center in reticular formation of brainstem Phases: oropharyngeal (voluntary) and esophageal (involuntary) Must coordinate with respiratory center • Respiration is inhibited – epiglottis slides downward to prevent food from entering larynx and trachea o Peristalsis: Primary: immediately follows oropharyngeal phase of swallowing Secondary: bolus of food becomes stuck – wave of contraction and relaxation occurs that is independent of voluntary swallowing • Stomach o Hollow muscular organ – stores food, secretes digestive juices, mixes food with juices – propels chyme into duodenum o Muscle layers – outer (longitudinal), middle (circular), inner (oblique) o Sphincters – lower esophageal (chyme enters from esophagus into stomach), pyloric (chyme exits stomach into duodenum of small intestine o Functional portions – upper (fundus), middle (body), lower (antrum) o Blood supply via branch of celiac artery; drainage via splenic vein and tributaries o Few substances absorbed in stomach – can absorb alcohol, aspirin, NSAIDS o Innervated by sympathetic and parasympathetic o Gastric motility Swallowing causes fundus to relax Gastrin and cholecystokinin enhance relaxation of stomach Gastrin and motilin and low blood glucose enhance peristalsis Sympathetic activity, secretin, cholecystokinin inhibit peristalsis Vagus nerve (parasympathetic) stimulates gastric secretion and motility Gastric mixing enhanced by retropulsion Gastric emptying • Increased by larger volumes of food • Delayed by solids, fats, and non-isotonic solutions - Fat – cholecystokinin – inhibits intake, gastric motility, decreases gastric emptying so that fats do not exceed rate of bile and enzyme secretion -Suppress cell division and shorten villi: starvation, vit B12 deficiency, cytotoxic drugs, irradiation –> leads to diarrhea and malnutrition -Stimulate cell production: nutrient intake and intestinal resection • Large intestine o Massages fecal mass; absorbs water and electrolytes o Parts: ▪ Cecum: pouch that receives chyme from the ileum ▪ Appendix: attached to the cecum ▪ Colon: ascending, transverse, descending, sigmoid ▪ Rectum and anus o Mucous secreting cells (goblet cells) in the mucosa but NO VILLI o Valves and sphincters: ▪ Ileocecal valve: admits chyme from ileum to cecum ▪ O’Beirne sphincter: controls movement of wastes from the sigmoid colon into the rectum ▪ Internal anal sphincter: smooth muscle ▪ External anal sphincter: striated skeletal muscle Basics of digestion and absorption; what happens where • Mouth o Breaks down food, mixes with saliva – initiates digestive process with salivary amylase • Esophageal sphincters o Upper sphincter prevents air from entering stomach o LES (cardiac sphincter) prevents regurgitation of food mass into esophagus • Stomach o Secretes pepsinogen, gastrin, and HCl acid that mix with food to form chyme ▪ Parietal cells secrete acid – pump H+ into stomach in exchange for K+ • Stimulated by gastrin, histamine, acetylcholine; inhibited by somatostatin, prostaglandins, secretin, vasoactive intestinal peptide ▪ Mucous cells secrete mucosal protective layer – secretion mediated by prostaglandins o Intrinsic factor secreted to absorb vitamin B12 in the small intestine o Nu nutrients are absorbed – only alcohol, aspirin, NSAIDS... • Small intestine o Duodenum receives chyme from the stomach through the pyloric valve -Absorbs vitamins, minerals, fats and sugars o Chyme stimulates liver and gallbladder to deliver bile and the pancreas to deliver digestive enzymes and alkaline secretions -Bile and enzymes flow through opening guarded by sphincter of Oddi o Jejunum absorbs carbs and proteins across intestinal mucosa by active transport into the villus capillaries o Ileum absorbs bile salts, vitamin B12, and chloride o All nutrients are absorbed in the small intestines as well as 85% of the water and fluid intake • Colon o Cecum pouch connects the large intestine to the small intestine which is where the appendix is o Serves as a reservoir for fecal mass and absorbs water and electrolytes – no nutrient absorption o Feces (excrement) enters sigmoid colon – consists of food residue, unabsorbed GI secretions, shed epithelial cells, bacteria ▪ Defecation reflex (retrosphincteric reflex): rectal wall stretches and tonically constricted internal anal sphincter relaxes creating urge to defecate – can be voluntarily overridden • Nutrients and absorption: o Carbohydrates digested into monosaccharaides and disaccharides ▪ Salivary and pancreatic amylases break down starches ▪ Sugars are primary absorbed in the duodenum and in the upper jejunum ▪ Glucose transporter 2 (GLUT2) facilitates transfer from cytosol to bloodstream – secondary active cotransport with sodium (Na/K-ATPase pump) ▪ Humans lack enzymes to digest cellulose o Proteins digested into amino acids and peptides ▪ Pancreatic enzymes accomplish major protein hydrolysis in small intestine -Trypsin and chymotrypsin: hydrolyze the bonds of large molecules (endopeptidase) -Carboxypeptidase: breaks away the end amino acids (exopeptidase) ▪ Sodium dependent carrier actively transports amino acids from cytosol to bloodstream ▪ Free amino acids can be absorbed directed from the intestinal lumen using membrane transport protein – secondary active cotransport with sodium (Na/K-ATPase pump) o Fats digested into fatty acids and monoglycerides ▪ 1. Emulsification: emulsifying agents cover the small fat particles and prevent them from re- forming into fat droplets • Ready for lipolysis – lipase breaks down triglycerides; phospholipase cleaves fatty acids from phospholipids; cholesterol esterase breaks cholesterol esters ▪ 2. Micelle formation: fatty acids and monoglycerides must be made water soluble to be absorbed – micelles ▪ 3. Fat absorption – passive via simple diffusion ▪ 4. Resynthesized triglycerides and phospholipids: absorbed as chylomicrons and eventually enter systemic circulation • Excess bind with apoproteins and transfer to systemic circulation o Minerals and vitamins ▪ Most minerals absorbed by passive diffusion or active transport – with carrier protein ▪ Most water-soluble vitamins are passively absorbed or by sodium-dependent active transport • Intestinal motility: o Peristalsis – contractions of circular muscles (segmentation) mixes chyme and promotes digestion o Ileogastric reflex inhibits gastric motility when the ileum is distended o Intestinointestinal reflex inhibits intestinal motility when one intestinal segment is overdistended o Gastroileal reflex increases intestinal motility when gastric motility increases -Three reflexes prevent overloading, backup – keep things moving forward Basic functions of accessory organs; liver, gallbladder, exocrine pancreas • Liver o Structure: • Largest solid organ in the body; right (larger) and left lobes • Glisson capsule – fibroelastic capsule - contains blood vessels, lymphatics, nerves • Requires large amount of blood – receives from hepatic artery (oxygenated) and hepatic portal vein (deoxygenated) [70% of supply] • Hepatocytes are the functional cells of the liver • Synthesize 700-1200 mL of bile per day and secrete into bile canaliculi – small channels between hepatocytes that can drain bile into the common bile duct and then into the duodenum through sphincter of Oddi • Lipocytes are star shaped cells that store lipids including vitamin A • Kupffer cells (mononuclear phagocyte system) are phagocytic cells - central to innate immunity • Stellate cells contain retinoids (vitamin A) - are contractile in liver injury, regulate sinusoidal blood flow, may proliferate into myofibroblasts, participate in liver fibrosis, remove foreign substances from the blood and trap bacteria • Pit cells are natural killer cells - important in tumor defense o Function: ▪ Enterohepatic circulation – choleresis -Recycling of bile salts -Choleretic agent: substance that stimulates the liver to secrete bile -High concentration of bile salts is a strong stimulus – as well as secretin, cholecystokinin, and vagal stimulation ▪ Formation of bilirubin – see below ▪ Vascular and hematologic functions -Stores blood, removes bacterial and foreign particles, synthesizes clotting factors ▪ Metabolizes fats • Bile absorbs fat-soluble vitamins; hydrolyzed triglycerides produce ATP or are secreted into blood stream bound to proteins (lipoproteins) ▪ Synthesizes phospholipids and cholesterol ▪ Metabolizes proteins • Deamination: the removal of ammonia (converted to urea and secreted in urine) converts amino acids into carbohydrates ▪ Metabolizes carbohydrates -Liver releases glucose during hypoglycemia; takes up glucose during hyperglycemia; stores glucose as glycogen (glyconeogenesis) or converts it to fat -When all glycogen stores are used, amino acids and glycerol are converted to glucose ▪ Metabolic detoxification • Biotransformation – makes toxic substances less harmful ▪ Storage of minerals and vitamins – release as needed ▪ Produces bile to absorb fat-soluble vitamins • Vitamin K – essential for synthesis of clotting factors; absorption depends on ▪ Pelvic floor dysfunction (pelvic floor dyssynergia or animus): failure of the pelvic floor muscles or anal sphincter to relax with defecation ▪ Secondary: from an actual disease process, condition, or meds o Clinical manifestations: Two of the following for at least 3 months -Straining with defecation 25% of the time; lumpy or hard stools at least 25% of the time; sensation of incomplete emptying 25% of the time; manual maneuvers to facilitate stool evacuation at least 25% of the time; fewer than 3 bowel movements per week o Fecal impaction: hard, dry stool retained in rectum • Diarrhea o Increased frequency of bowel movements – increased volume, fluidity, weight of feces o Often a protective mechanism – can be acute or chronic o Large-volume diarrhea: volume of feces is increased – caused by excessive amounts of water or secretions or both in intestines o Small-volume diarrhea: volume of feces is not increased – result of increased intestinal motility o Systemic effects are dehydration, electrolyte imbalance, metabolic acidosis, and weight loss o Steatorrhea (fat in stools) and diarrhea are common signs of malabsorption syndromes o Types: ▪ Osmotic • Nonabsorbable substance in the intestine draws water into the lumen by osmosis causing large volume diarrhea • Ex: lactose deficiency, magnesium sulfate, magnesium phosphate ▪ Secretory • Form of large volume diarrhea caused by excessive mucosal secretion of chloride or bicarbonate-rich fluid or the inhibition of net sodium absorption • Ex: bacterial enterotoxins – E. coli, neoplasms ▪ Motility • Excessive motility decreases transit time, mucosal surface contact, and opportunities for fluid absorption • Ex: resection of small intestine, short bowel syndrome, abnormal fistula o Systemic manifestations ▪ Acute bacterial or viral infection – fever with or without cramping pain ▪ Inflammatory bowel disease – fever, cramping pain, bloody stools ▪ Malabsorption syndromes – steatorrhea and diarrhea • Fecal characteristics o Shape: narrow or ribbon like may reflect obstruction in lower GI tract o Bloody stools: lower GI bleed, inflammatory bowel disease, bacterial infection o Black, tarry: upper GI bleed, Pepto Bismol intake, increased iron intake o Blood with stool: lower GI problem, hemorrhoids, cancer, ruptured diverticulum o Clay-colored: gallbladder or liver disease (decrease in conjugated bilirubin) o Frothy, fatty (steatorrhea): problems with fat digestion, children with CF, adults with pancreatic disease or cholecystitis – indicates loss of bile (necessary for fat digestion) ABD pain, basic patho, types • Patho: from stretching, inflammation or ischemia o Biochemical mediators of the inflammatory response: histamine, bradykinin, serotonin – stimulate pain nerve endings producing abdominal pain • Types: o Parietal (somatic pain): in the peritoneum ▪ Localized, intense o Visceral pain: in the organs themselves ▪ Poorly localized, diffuse, vague o Referred pain: felt in another area, usually the back ▪ Is visceral pain intensified – share afferent nerve pathway ▪ Due to distant inflammation, ischemia • Locations o RUQ: liver, gallbladder, bile duct o RLQ: appendix, right ovary/fallopian tube o LUQ: stomach, gastroesophageal junction, spleen o LLQ: desc. colon (diverticular site),left ovary/fallopian tube o Bilateral posterior: kidneys/ureters; bilateral anterior: ovaries o Midline posterior: aorta; upper midline posterior: pancreas, aorta o Lower midline anterior: uterus, bladder Dysphagia Difficulty swallowing • Types: o Mechanical obstruction of the esophagus ▪ Intrinsic: in wall of the esophageal lumen (tumors, strictures, diverticular herniations ▪ Extrinsic: outside esophageal lumen and narrow esophagus by pressing inward (tumors) o Functional disorder that impairs esophageal motility ▪ Caused by neuronal or muscular disorders that interfere with voluntary swallowing or peristalsis – CVA, Parkinson’s *Clinical manifestations: depends on location o Distention and spasm cause stabbing pain at level of obstruction o Upper obstruction: discomfort 2-4 seconds after swallowing o Lower obstruction: discomfort 10-15 seconds after swallowing o Tumor: begins with difficulty swallowing solids and leads to difficulty swallowing liquids o Neuromotor function loss: difficulty beginning with both solids and liquids o All types: retrosternal pain, regurgitation of undigested food, unpleasant taste, vomiting, and weight loss – complication: aspiration pneumonia GERD • Acid and pepsin refluxes from the stomach into the esophagus causing esophagitis • Resting tone of the lower sphincter tends to be lower than normal from transient relaxation or weakness • Conditions that increase abdominal pressure can contribute – vomiting, coughing, lifting, bending, obesity • Risk factors: obesity, H. Pylori Types: o Physiologic reflux: does not cause symptoms -LES relaxes and regurgitation of gastric contents into esophagus – acid is neutralized and cleared by peristaltic action in esophagus in 1-3 minutes and LES tone is restored o Nonerosive reflux (NERD): symptoms of reflux disease but no visible mucosal injury o Reflux esophagitis: combination of factors causes injury and inflammation • Clinical manifestations: o Heartburn, regurgitation of acidic chyme, and upper abdominal pain within 1 hour of eating o S/Sx worsen if person lies down or if intra-abd pressure increases (vomiting, coughing) • Association with GERD and: laryngitis, asthma, chronic cough Gastritis Inflammatory disorder of the gastric mucosa -Acute o Associated with H.Pylori, NSAIDS, drugs, chemicals o Clinical manifestations: vague abdominal discomfort, epigastric tenderness, bleeding -Chronic o Fundal (upper) gastritis ▪ Immune, type A ▪ Autoantibodies to parietal cells and intrinsic factor – gastric atrophy and pernicious anemia o Antral (lower) gastritis ▪ Nonimmune, type B ▪ Associated with H.Pylori and NSAIDS • Malabsorption: failure of the intestinal mucosa to absorb (transport) the digested nutrients o Common causes: bile salt deficiencies, enzyme deficiencies, bacterial infections, disruption of mucosal lining, disturbed lymphatic and vascular circulation, loss of gastric or intestinal surface area • Examples: o Celiac disease: inborn error of metabolism affects absorption of glutens (wheat, barley, rye, oats) o Pancreatic insufficiency: insufficient enzyme production – lipase, amylase, trypsin, chymotrypsin -Causes: pancreatitis, pancreatic carcinoma, pancreatic resection and CF -Leads to fat maldigestion – fatty stools (steatorrhea), weight loss o Lactase deficiency: congenital defect in lactase gene – inability to breakdown lactose – fermentation of lactose by bacteria, causing gas (cramping pain, flatulence) and osmotic diarrhea o Bile salt deficiency: conjugated bile salts are needed to emulsify and absorb fats and are synthesized from cholesterol in the liver – result of liver disease and bile obstructions -Poor intestinal absorption causes fatty stools, diarrhea, loss of fat-soluble vitamins • Vitamin A – night blindness • Vitamin D – decreased calcium absorption, bone pain, osteoporosis, fractures • Vitamin K – prolonged PT time, purpura, petechiae • Vitamin E – testicular atrophy, neuro defects in children Ileus types and basic patho and findings • Ileus: obstruction of the intestines – more common in small intestine (narrower) o Acute: mechanical causes; chronic/partial: tumors, inflammatory disorders (large intestine) • Small intestine obstruction: o Colicky pains caused by intestinal distention followed by nausea and vomiting • Large intestine obstruction: o Hypogastric pain and abdominal distention -Ex: colon cancer, diverticular strictures, twisting o Consequences related to the competence of the ileocecal valve o Ischemia occurs when intraluminal pressure exceeds capillary pressure in the lumen o Ogilvie syndrome: acute colonic pseudo-obstruction – massive dilation of large bowel that occurs in critically ill patients and immobilized older adults – characterized by dilation of the cecum and absence of mechanical obstruction •Obstruction leads to accumulation of fluid and gas inside lumen proximal to obstruction – impair water and electrolyte absorption and enhanced secretion with net movement of fluid from vascular space into intestinal lumen – distention – decreased ability to absorb water and electrolytes – increases net secretion of gastric juice, bile, pancreatic juice and intestinal secretions • Location and type of vomit: o Pyloric: early, profuse vomiting of clear, gastric fluid o Proximal small intestine: mild distention and vomiting of bile-stained fluid o Lower in small intestine: more pronounced distention because a greater length of intestine is proximal to the obstruction; vomiting may or may not occur later and contain fecal matter Ulcerative colitis and Crohn’s disease • Ulcerative colitis : chronic inflammatory disease the causes ulceration of the colonic mucosa of sigmoid colon and rectum o Causes: infectious, immunologic, dietary, genetic o Patho: lesions are continuous with no skipped lesions – limited to mucosa – not transmural o Clinical manifestations: diarrhea (10-20/day), bloody stools, crampy lower abd pain relieved by defecation – remissions and exacerbations • Chron’s o Most commonly affects distal small intestine and proximal large colon o Similar risk factors and causation as UC – strong association with CARD12/NOD2 gene mutations o Patho: skip lesions – inflammation affects some segments but not others – ulcerations produce longitudinal and transverse inflammatory fissures that extend into lymphoid tissue - “cobblestone” o Clinical manifestations: abd pain and diarrhea (>5/day) with passage of blood and mucus; inflammation of ileum causes RLQ tenderness; weight loss -Anemia may result from vitamin B12 and folic acid; bone disease from malabsorption of calcium; protein loss leads to hypoalbuminemia disease: idiopathic inflammatory disorder affecting any part of the digestive tract Diverticular disease; types and basic clinical manifestations and patho • Types o Diverticula: herniations of mucosa through muscle layers of the colon wall (esp. L sigmoid colon) o Diverticulosis: asymptomatic diverticular disease o Diverticulitis: inflammatory stage of diverticulosis; inflammation of the diverticula • Patho o Habitual consumption of low-residue diet reduces fecal bulk – reduces diameter of the colon – pressure within the narrow lumen can increase enough to rupture the diverticula -Also decreases immune response in the colon and permits low-grade inflammation o Diverticulitis can cause abscess formation, peritonitis, or obstruction – risk of perforation • Clinical manifestations o Usually vague or absent o Cramping pain of lower abd – exacerbated by eating, diarrhea, constipation, distention, flatulence o Incomplete relief of pain after defecation o Abscess – fever, leukocytosis, tenderness of LLQ o RLQ pain w/ complications – hemorrhage, perforation w/ peritonitis, bowel obstruction, and fistula IBS •Functional gastrointestinal disorder with no specific structural or biochemical alterations • Characterized by recurrent abdominal pain and discomfort associated with altered bowel habits that present as diarrhea or constipation or both • Clinical manifestations: o Can be diarrhea or constipation predominant; alternating diarrhea/constipation, gas, bloating, nausea o Symptoms relieved with defecation and don’t interfere with sleep o Associated with anxiety, depression, and chronic fatigue syndrome • Cause: unknown – may be related to visceral hypersensitivity, abnormal intestinal motility and secretion, intestinal infection, overgrowth of small intestinal flora, food allergy/intolerance, psychosocial factors Obesity • Increase in body fat mass o Overweight: BMI greater than 25 kg/m2 o Obesity: BMI greater than 30 kg/ m2 • Adipocyte: cellular basis of obesity • Orexins: molecules that stimulate eating – hypocretins from the hypothalamus. • Anorexins: molecules that inhibit eating • Types: o Visceral: intrabdominal, central, apple shape o Peripheral: gluteal-femoral, subcutaneous, pear shape Appendicitis • Inflammation of the vermiform appendix – most common surgical emergency of the abdomen • Patho: obstruction by inflammatory process, foreign body, or neoplasm -Normally polymicrobial process: Enterobacteriaceae, anaerobes, enterococcus -Obstruction of the lumen leads to increased pressure, ischemia, and inflammation of the appendix Clinical manifestations o 96% of patients will exhibit epigastric and RLQ pain – begins vague and increases in intensity – followed by N/V, anorexia; fever is common; diarrhea in children o Rebound tenderness: RLQ pain is associated w/ extension of the inflammation to surrounding tissues; pain when releasing palpation **Without surgical resection – inflammation – gangrene, perforation, peritonitis Cholelithiasis and Cholecystitis • Cholelithiasis: gallstone formation – cholesterol stone formation in bile that is supersaturated with cholesterol o Causes: enzyme defect causing increased cholesterol synthesis; decreased secretion of bile acids Portal hypertension • Abnormally high blood pressure in the portal venous system caused by resistance to portal blood flow • Three regions affected: o Prehepatic (portal vein): caused by thrombosis or narrowing of the portal vein o Intrahepatic (within the liver): from vascular remodeling with intrahepatic shunts, thrombosis, inflammation, or fibrosis of the sinusoids o Posthepatic (hepatic vein): occur from hepatic vein thrombosis or cardiac disorders (right sided heart failure or constrictive pericarditis) that impair the pumping ability of the right heart – blood backs up and increases pressure in portal system • High blood pressure in the portal veins causes collateral vessels to open between the portal veins and systemic veins; blood bypasses the obstructed portal vessels because blood pressure is considerably lower o Activates RAAS – increase renin – increased fluid retention – overload heart and liver further -Positive feedback • Consequences: o Varices: distended, tortuous, collateral veins caused by prolonged elevation in hepatic portal vein pressure causing veins to open and turn into varices ▪ Most common in lower esophagus and stomach – can also occur in abd wall and rect ▪ Rupture can cause life threatening hemorrhage o Splenomegaly: enlargement of the spleen – see below o Ascites: accumulation of fluid in the peritoneal cavity - see below o Hepatic encephalopathy: brain toxicity - see below • Clinical manifestations: vomiting of blood from esophageal varices is most common; and ascites Splenomegaly • Causes: portal HTN causes increased intrasplenic blood pressure • Clinical manifestations: most common is thrombocytopenia – increased bleeding tendency • Can be predictive of esophageal varices severity Ascites • Causes: cirrhosis – also by heart failure, constrictive pericarditis, abdominal malignancies, nephrotic syndrome, malnutrition • Contributing factors: portal HTN, splanchnic vasodilation, hepatocyte failure, sodium retention • Clinical manifestations: abdominal distention, increased girth, weight gain o Secondary: respiratory distress (displaced diaphragm), peripheral edema, dilutional hyponatremia o Complication: peritonitis – fever, chills, shock Hepatic encephalopathy • Accumulation of toxins related to liver failure causing a disruption of neurotransmission o Ammonia accumulates and is toxic to the brain • Clinical manifestations: personality changes, confusion, memory loss, flapping tremor (asterixis), stupor, coma, death – may slowly occur over time with chronic liver disease Jaundice •“icterus”: yellow or greenish pigmentation of the skin caused by hyperbilirubiinemia (>2.5-3) • Causes: o Extrahepatic obstruction to bile flow (gallstones) o Intrahepatic obstruction (from cirrhosis or hepatitis) o Prehepatic obstruction (excessive production of bilirubin from excessive hemolysis of RBC’s) • Clinical manifestations : dark urine, clay-colored stools, yellow discoloration in sclera and then skin, skin xanthomas (cholesterol deposits), pruritis Hepatitis, types and stages, basics of each type • Hepatic necrosis, Kupffer cell hyperplasia, infiltration of liver tissue by mononuclear phagocytes o Causes obstruction of bile flow and impairment hepatocyte function • Chronic active hepatitis: occurs with hepatitis B and C with a predisposition to cirrhosis and hepatocellular carcinoma • Fulminant hepatitis: complication of hepatitis B (with or without D) or hepatitis C – causes widespread hepatic necrosis – often fatal • Stages: o Incubation phase: varies depending on virus o Prodromal (pre-icteric) phase: begins approximately 2 weeks after expsoure; ends with appearance of jaundice -Clinical manifestations: fever, malaise, anorexia, hepatomegaly, tenderness; highly transmissible o Icteric phase: actual phase of illness -Clinical manifestations: jaundice, hyperbilirubinemia, fatigue and abdominal pain, increased bilirubin in serum, PT prolonged o Recovery phase: begins with resolution of jaundice -Symptoms resolve after several weeks – chronic or chronic active hepatitis may develop • Types: o Hepatitis A -Found in feces, bile, sera of infected individual – transmitted fecal-oral route -RNA hepatovirus – vaccine available o Hepatitis B -Transmitted through contact with infected blood, body fluids, contaminated needles -42-nm hepadnavirus with partially double stranded DNA genome -Maternal transmission during 3rd trimester if infected – vaccine available o Hepatitis C -Responsible for most cases of posttransfusion hepatitis; IV drug use, HIV *Up-regulation: low concentration of hormones increases number of receptors *Down-regulation: high concentration of hormones decreases number of receptors Basics of HPA axis what comes from where • Hypothalamic-pituitary axis forms the structural and functional bases for the central integration of the neurologic and endocrine systems – produces many releasing/inhibitory hormones and tropic hormones o Hypothalamus: base of the brain; connected to anterior pituitary by portal blood vessels; connected to posterior pituitary by nerve tract -Produces hormones: • Prolactin-inhibiting factor (PIF-dopamine): inhibition of prolactin • Thyrotropin-releasing hormone (TRH): release of TSH • Gonadotropin-releasing hormone (GnRH): release of LH/FSH • Somatostatin: inhibits release of GH and TSH • Growth hormone-releasing factor (GRF): release of GH • Corticotropin-releasing hormone (CRH): release of ACTH • Substance P: inhibition of ACTH o Posterior pituitary : stores and secretes hormones synthesized in the nuclei of the hypothalamus -Antidiuretic hormone (ADH) -Controls plasma osmolality; causes water reabsorption in the kidneys -Released when plasma osmolality is increased, or intravascular volume is decreased -Oxytocin -Causes uterine contractions and milk ejection in lactating women -Reduces brain’s responsiveness to stressful stimuli (esp. in pregnant/postpartum) *Mediated by cholinergic and adrenergic NT’s - glutamate (stimulus); GABA (inhibitory) o Anterior pituitary : hormones regulated by feedback of hypothalamic releasing-inhibitory hormones/factors, from target gland hormones (cortisol and estrogen), or direct effect of NT’s -Adrenocorticotropic hormone (ACTH) -Target organ: adrenal cortex/gland -Function: increase steroidogenesis (cortisol, androgenic hormones, aldosterone) -Melanocyte-stimulating hormone (MSH) -Target organ: pigment cells -Function: promotes secretion of melanin and lipotropin – makes skin darker -Luteinizing hormone -Target organ: granulosa cells (women); Leydig cells (men) -Function: ovulation, progesterone production (women); testicular growth, testosterone production (men) -Follicle-stimulating hormone -Target organ: granulosa cells (women); Sertoli cells (men) -Function: follicle maturation, estrogen production (women); spermatogenesis (men) -Thyroid-stimulating hormone -Target organ: thyroid -Function: increase production and secretion of thyroid hormone, increased iodine uptake, promotes hypertrophy and hyperplasia of thymocytes -Growth hormone -Target organ: muscle, bone, liver -Function: essential to normal tissue growth and maturation; affects aging, sleep, nutritional status, stress, and reproductive hormones o Controlled by two hormones from hypothalamus 1. Growth hormone-releasing hormone (GHRH): increases secretion 2. Somatostatin: inhibits growth hormone -Prolactin -Target organ: breast -Function: milk production; effects on reproductive and immune functions Pineal gland and thymus – NOT ON STUDY GUIDE • Pineal gland located within brain – made up of photoreceptive cells that secrete melatonin o Plays important role in circadian rhythms, reproductive systems (GnRH and puberty), immune regulation • Thymus – releases thymosin that stimulates T cell development in the immune system Thyroid and parathyroid gland; hormones; and basic physiology • Thyroid gland o Function: produces hormones that control rates of metabolic processes within the body o Structure • Two lobes lie just below larynx on either side of trachea; isthmus joins the two lobes • Composed of follicles (follicle cells) - synthesize and secrete some thyroid hormones • Parafollicular cells (c-cells) - secrete calcitonin - lower serum calcium levels by inhibition of osteoclasts o Hormones ▪ Regulation of thyroid hormone secretion is by TRH from hypothalamus – stimulates TSH from anterior pituitary – TSH increases release of thyroid hormones, iodine uptake and oxidation, thyroid hormone synthesis, and synthesis and secretion of prostaglandins by the thyroid gland • TSH responds to low levels of circulating thyroxine through negative feedback ▪ Thyroid hormone (TH)/thyroxine/T4: precursor to triiodothyronine (T3) ▪ Triiodothyronine (T3): regulates metabolic rate of all cells and processes cell growth ▪ Circulating levels of TSH are used to monitor thyroid conditions and hormone levels -TSH high: decrease or insufficient level of TH has occurred – hypothyroidism -TSH low: increase or excess level of TH has occurred – hyperthyroidism • Parathyroid glands o Structure: small glands located behind the thyroid gland o Hormones ▪ Parathyroid hormone -Regulates serum calcium, increases calcium concentration, decreases phosphate level, acts as co-factor w/ vitamin D to increase calcium absorption -Antagonist to calcitonin Endocrine pancreas, cells and what their function is - which cells release what • Pancreas is both an endocrine (glucagon and insulin) and exocrine (digestive enzymes) gland • Islets of Langerhans: secretion of glucagon and insulin - help regulate carb metabolism • Hormone secreting cells: o Alpha: secrete glucagon – see below o Beta: secrete insulin and amylin – see below o Delta: secrete somatostatin and gastrin ▪ Somatostatin: essential in carb, fat, and protein metabolism; may prevent excess insulin secretion ▪ Gastrin: controls secretion of glucagon ▪ Ghrelin: stimulates GH secretion, controls appetite, regulation of insulin sensitivity o F cells/PP cells: secrete pancreatic polypeptide ▪ PP: released in response to low blood glucose and protein rich meals and signals satiety; increases gastric acid secretion; increased in pancreatic tumors and diabetes ANS innervation of pancreatic islets what does the SNS and PSNS do? • Sympathetic nervous system o Stimulates alpha cells of pancreas to release glucagon o Need glucose/energy for “fight or flight” • Parasympathetic nervous system o Stimulates beta cells of pancreas to release insulin, secretion of pancreatic juice o “rest and digest” Insulin what is its function where does it come from • Comes from beta cells and synthesized from proinsulin • Function o Anabolic hormone that promotes synthesis of proteins, lipids, and nucleic acids o Facilitates rate of glucose uptake into cells of the body - controls blood glucose levels o Facilitates intracellular transport of potassium, phosphate, and magnesium into cells o Secretion is regulated by chemical, hormonal, and neural control • 1. Failure of feedback systems • 2. Dysfunction of an endocrine gland – excessive or inadequate production • 3. Altered hormone – inactivation or degradation • 4. Ectopic hormone release from non-endocrine sites or autonomous production • 5. Failure of target cell to respond to its hormone – receptor disorder, intracellular disorder SIADH basic patho and causes, what happens in the body with SIADH? What type of hyponatremia is present? Clinical manifestations? • Patho: o Levels of antidiuretic hormone (ADH) are abnormally high o Most common cause: ectopic secretion of ADH; also, after surgery and some cancers o Water retention: action of ADH on renal collecting ducts increases their permeability to water, thus increasing water reabsorption by the kidneys o For diagnosis, normal renal, adrenal, and thyroid function must exist o Nephrogenic form: excess free water; genetic form – mutation in arginine vasopressin AVP gene • Clinical manifestations: o Characterized by euvolemic hypotonic (dilutional) hyponatremia -Total body water: increased -Total body sodium: unchanged -Extracellular fluid: increased -Edema: absent o Hyponatremia, serum hypoosmolality (<280 mOsm), urine hyperosmolality, euvolemia (no signs of volume change), weight gain, headache, N/V, confusion; severe hyponatremia can lead to coma, convulsions, death DI basic patho, causes, clinical manifestations? Types? • Patho: o Insufficiency of antidiuretic hormone (ADH) o Types: • Neurogenic (central): deficiency in the brain; insufficient amounts of ADH produced • Nephrogenic (renal): kidneys don’t react to ADH; insensitivity of the renal collecting tubules to ADH • Genetic (x-linked) or acquired (meds, 2nd messenger defect, CKD, hypercalcemia, hypokalemia, cancer) • Dipsogenic/psychogenic: excessive fluid intake – lowers plasma osmolarity to the point that it falls below the threshold for ADH secretion o Clinical manifestations: ▪ Characterized by the inability of the kidney to decrease permeability to water ▪ Excretion of large volumes of dilute urine, increase in plasma osmolality (>300 mOsm), Hypopituitarism; panhypopituitarism; basic patho, what they are? What deficiencies do you see and basic results of the deficiencies? • Patho : o The absence of selective pituitary hormones or the complete failure of all pituitary hormone functions (panhypopituitarism) • The pituitary is vascular and therefore vulnerable to ischemia and infarction • Necrosis leads to edema with swelling of the gland – over time pituitary undergoes shrinkage and symptoms of hypopituitarism develop • Hormones affected: o ACTH (adrenocorticotropic hormone) deficiency ▪ Cortisol deficiency o TSH deficiency ▪ Altered metabolism o FSH and LH deficiency ▪ Lack of secondary sex characteristics o GH deficiency ▪ Lack of growth in children Hyperpituitarism; acromegaly patho, what happens to the body (manifestations), gigantism what is it and which bones does it affect? • Patho: o Commonly from benign, slow-growing pituitary adenoma • Clinical manifestations: o Headache and fatigue, visual changes (close to optic chiasm), CN palsies, hypersecretion of pituitary from tumor, hyposecretion of neighboring anterior pituitary hormones (hypocortisol and hypothyroid) • Giantism: o GH hypersecretion in children and adolescents – effects long bone growth • Acromegaly: o GH hypersecretion in adulthood – mostly caused by slowly progressive pituitary adenoma o Mortality: cardiac hypertrophy, HTN, atherosclerosis, type 2 DM – CAD o Other malignancies common o Connective tissue proliferation -Enlarged tongue, interstitial edema, increase in size and function of sebaceous and sweat glands, coarse skin and body hair o Bony proliferation -Large joint arthropathy, kyphosis, enlargement of facial bones and hands and feet, protrusion of lower jaw and forehead, need for increasingly larger sized shoes, hats, rings, and gloves o Symptoms of diabetes -Polyuria and polydipsia o CNS symptoms -Headache, seizure activity, visual disturbances, papilledema • hypersecretion of prolactin: most common hormonally active pituitary tumor o Women: amenorrhea, galactorrhea, hirsutism, osteoporosis o Men: hypogonadism, ED, impaired libido, decreased ejaculation volume with no sperm Hyperthyroidism; thyrotoxicosis, primary, secondary, manifestations, Graves' disease, thyroid storm • Hyperthyroidism/thyrotoxicosis o A condition that results from any cause of increased level of thyroid hormone – excess secretion o Primary: -Dysfunction of disease of the thyroid gland or anything that alters TH production o Secondary: -Conditions that cause alterations in pituitary or hypothalamic functioning; alters TSH or thyrotropin-releasing hormone (TRH) production o Clinical manifestations: -Increased metabolic rate with heat intolerance and increased tissue sensitivity to stimulation by the sympathetic nervous system; enlargement of the thyroid gland (goiter) -Thin hair, normal or enlarged thyroid that may be warm on palpation or nodular, heart failure (tachycardia), weight loss, diarrhea, warm skin with sweaty palms, hyperreflexia • Graves’ disease o Patho: ▪ Autoimmune hyperthyroid condition that develops autoantibodies (type II hypersensitivity reaction) towards the thyroid – **most common cause o Clinical manifestations: ▪ Ophthalmopathy – exophthalmos: increased secretion of hyaluronic acid, orbital fat accumulation, inflammation, and edema of the orbital contents; diplopia: double vision ▪ Pretibial myxedema (Graves’ dermopathy): leg swelling “orange peel appearance” • Thyrotoxic crisis (thyroid storm) o Rare but life threatening within 48 hours if not treated o Results from excessive stress on patients with hyperthyroidism that’s either undiagnosed or underdiagnosed – ex of stress: infection, trauma, burns, surgery ▪ Increased action of thyroxine (T4) and triiodothyronine (T3) o Clinical manifestations: ▪ Hyperthermia, tachycardia, atrial tachydysrhythmias, high output heart failure, agitation or delirium, N/V/D • Hyperthyroidism resulting from nodular thyroid disease o Toxic multinodular goiter: several hyperfunctioning nodules secrete thyroid hormone o Solitary toxic adenoma: only one nodule becomes hyperfunctioning o Clinical manifestations: ▪ Same as hyperthyroidism but occur slowly; exophthalmos & pretibial myxedema don’t occur Hypothyroidism; primary, secondary, clinical manifestations, myxedema coma • Patho: o Deficient production of thyroid hormone by the thyroid gland o Primary: ▪ Inability of the thyroid gland to produce TH o Type 1: pancreatic atrophy and loss of beta cells ▪ Autoimmune • Environmental and genetic factors trigger cell-mediated destruction of beta cells o Environmental: viral infection, h. pylori, exposure to cow’s milk proteins, relative lack of vitamin D o Genetic: first-degree relative with type 1 DM, association with MHC • Autoantibody, t-cell and macrophage destruction of pancreatic beta cells occur with a loss of insulin production and relative excess of glucagon o 1. lymphocyte and macrophage infiltrate islets – inflammation and islet beta cell death o 2. autoantibodies are produced against islet cells, inulin, glutamic acid decarboxylase, and other cytoplasmic proteins o Both alpha and beta cell functions are abnormal, and both lack insulin and amylin and have relative excess of glucagon – hyperglycemia, hyperketonemia • Human leukocyte antigens are associated ▪ Non-immune • Occurs secondary to other diseases – pancreatitis, idiopathic diabetes ▪ Clinical manifestations: -80-90% loss of function of beta cells before hyperglycemia develops -Polydipsia, polyuria, polyphagia, weight loss, fatigue o Type 2: insulin resistance and decreased insulin secretion by beta cells • Beta cell dysfunction: beta cell mass is decreased; elevated FFA hyperglycemia, adipokines, and inflammatory cytokines promote apoptosis of beta cells • Glucagon: pancreatic alpha cells are less responsive to glucose inhibition resulting in increased glucagon release – increase hepatic production of glucose – further contributing to hyperglycemia • Amylin: decreased in type 1 and type 2 • Ghrelin: decreased in type 2 • Risk factors : age, obesity, HTN, physical inactivity, family history, metabolic syndrome • Metabolic syndrome: central obesity, dyslipidemia, prehypertension, elevated fasting blood glucose level • Genetic, epigenetic, and environmental interactions; must be genetically predisposed • More common than type 1, affecting both adults and children • Clinical manifestations • Fatigue, pruritis, recurrent infections, visual changes, neuropathy Other types --- o Gestational : any degree of glycose intolerance with the onset or first recognition occurring during pregnancy • Recommended that if high risk women are found to have diabetes at first prenatal visit that they receive diagnosis of overt diabetes • Contributing factors: insulin resistance and inadequate insulin secretion; gestational diabetes increases risk for development of type 2 diabetes Complications of DM hypoglycemia, DKA, HHNKS (know differences between DKA and HHNKS and how they present), Somogye effect, dawn phenomenon; basic patho of each • Hypoglycemia o Lowered plasma glucose level – newborns <35; children and adults <50 o Most commonly caused by excess exogenous insulin but may result from meds and is precipitated by change in quantity and timing of activity and food o Clinical manifestations: ▪ Parasympathetic activation (hunger) and sympathetic activation (tachycardia, palpitations, diaphoresis, tremors, pallor, arousal anxiety) • DKA o Absolute or relative deficiency of insulin and an increase in insulin counterregulatory hormones o Precipitating factors: illness, trauma, surgery, MI – most common in type 1 DM o Increased fat mobilization with the release of fatty acids (fat catabolism) leads to increased ketone production and DKA o Clinical manifestations: ▪ Polyuria, dehydration, Kussmaul respirations, sweet or fruity breath ▪ Labs: serum glucose >250, serum pH <7.30, urine ketones, total body potassium depletion • Serum potassium may appear normal or elevated because of fluid shifts and H+ into the cell and K+ out because of acidosis • Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS) o Hyperglycemic hyperosmolar state (HHS) ▪ Amount of insulin required to inhibit fat breakdown is less than that needed for effective glucose transport, insulin levels are sufficient to prevent excessive lipolysis but not to use glucose properly o Precipitated by: infections, meds, nonadherence to diabetes treatment, co-existing disease – life threatening emergency usually associated with type 2 DM o Some insulin deficiency (less than in DKA) o Fluid deficiency (more than in DKA) o Elevated glucose levels (more than in DKA) o Clinical manifestations: ▪ Glycosuria, polyuria, dehydration, coma ▪ Labs: glucose >600, absent or low urine ketones *lack of ketosis* • Differences between DKA and HHNKS •Somogyi effect o Hypoglycemia with rebound hyperglycemia – *an over-compensation of hypoglycemia o Counterregulatory hormones (catecholamines, cortisol, glucagon) cause gluconeogenesis from non-carb substances and increased glycogenolysis (breakdown of glucagon) o Most common in type 1 DM and children • Dawn phenomenon o Early morning glucose elevation without nocturnal hypoglycemia o Related to nocturnal growth hormone elevation o More severe with adolescents/young adults but affects all people with DM (GH peak at younger age) Basics of chronic complications of DM and basic patho (micro and macrovascular disease processes) • Microvascular disease : disease in the capillaries caused by diabetes o Thickening of the capillary basement membrane, endothelial cell hyperplasia, thrombosis, and pericyte degeneration; hyperglycemia must be present; leads to tissue hypoxia and ischemia o Diabetic retinopathy ▪ Leading cause of blindness worldwide; more rapid development in type 2 DM ▪ Maculopathy: progressive process that accompanies retinal capillary permeability, vessel occlusion, and ischemia ▪ Macular edema: fluid accumulation and retinal thickening o Diabetic nephropathy ▪ Most common cause of end-stage kidney disease in the western world ▪ Progressive changes include glomerular enlargement, glomerular basement membrane thickening, injury to the glomeruli by protein denaturation (leads to proteinuria) o Diabetic neuropathy ▪ Most common complication of diabetes ▪ Sensory deficits precede motor involvement ▪ Distal portions of the neurons are initially and eventually more severely affected o Addisonian crisis: severe hypotension and vascular collapse ▪ Combined effects of hypocortisolism (decreased vasomotor tone), hypoaldosteronisms and extracellular volume depletion from precipitating stressor (infection, V/D) • Secondary hypocortisolism o Prolonged administration of exogenous glucocorticoids which suppress ACTH secretion o Clinical manifestations: ▪ Similar to Addison's disease except hyperpigmentation does not occur, RAAS system is normal so normal aldosterone and potassium levels Adrenal medulla dysfunction/hypersecretion; pheochromocytomas • Pheochromocytoma: hyperfunction from a tumor of the adrenal medulla derived from the chromaffin cells of the adrenal medulla that secrete catecholamines (epi/norepi) • Risks: familial forms associated with RET proto-oncogenes, VHL gene (tumor suppressor gene) • Clinical manifestations: o Hypertension, diaphoresis, tachycardia, palpitations, severe headache, glucose intolerance, hypermetabolism; *excessive fight or flight response • Tumors are highly vascular and can rupture causing massive and possibly fatal hemorrhage o Sudden, unexplained decrease in blood pressure, severe abdominal pain, and rigid abdomen **There is no hypofunction of the adrenal medulla identified; only hyperfunction REPRODUCTION PHYSIOLOGY Basics of sexual differentiation, dependent on sex hormones, SRY role • Sexual differentiation in utero o Initially male and female are homologous o Gonads – 6-8 weeks testes form and begin to differentiate or ovaries form in absence of testosterone • Dependent on sex hormone o Males: testosterone – testes-determining factor is needed – sex-determining region on Y chromosome (SRY) is expressed and male gonadal development prevails o Females: estrogen, FSH, LH • Structure and function of male and female reproductive systems are controlled by HPG axis o Set of complex neurologic and hormonal interactions that accelerated at puberty and lead to sexual maturation and reproductive capability Negative feedback system • Present at term pregnancy • Gonadostat responds to placental estrogen – release of gonadotropin-releasing hormone (GnRH) • Soon after birth, sex hormones drop precipitously because of withdrawal of placental steroid hormones • Negative feedback action of the sex steroids on the hypothalamus and pituitary is removed and the gonadotropins LH and FSH are released • Feedback mechanism is probably an intrinsic neuronal inhibitory system which suppresses endogenous GnRH secretion and gonadotropin synthesis Basics of puberty • Onset of sexual maturation ▪ Girls -Begins at 8-9 years with thelarche – breast development; menarche 1-2 years after o Obese girls mature earlier – higher estrogen levels related to leptin and gonadotropin secretion -Ovaries begin to release mature ova o FSH stimulates growth of ovarian follicles and with LH stimulates ovarian estradiol production o Early estradiol stimulates breast development and growth of skeletal pubertal growth spurt o Later – interaction of pituitary secretion of FSH, LH and estradiol – ovulation/menstrual cycles o Complete at first ovulatory menstrual period ▪ Boys -Begins at 11 years; voice changes, enlarged testes, scrotum, sperm in ejaculation -Testes begin to produce mature sperm o LH stimulates Leydig cells to produce testosterone with high concentration – stimulates growth of seminiferous tubules – increased testicular volume o FSH stimulates further growth of tubules and testicular volume o Testosterone induces growth of penis, deepening of voice, growth of hair, increased masculinity o Complete with first ejaculation that contains mature sperm • Involves the hypothalamic pituitary gonadal (HPG) axis, CNS, and endocrine system o Hormones: ▪ Estradiol: breast development, maturation of vagina, uterus, ovaries; fat deposits in hips ▪ Estrogen and increased production of growth factors: rapid skeletal growth in boys and girls ▪ Testosterone: growth of testes, scrotum, and penis ▪ Positive feedback loop: created to produce more sex hormones • Extrahypothalamic factors: o Cause the hypothalamus to secrete gonadotropin-releasing hormone (GnRH) o GnRH stimulates the anterior pituitary gland to secrete gonadotropins (FSH and LH) o FSH and LH: stimulate the gonads (ovaries or testes) to secrete female or male sex hormones o Paracrine hormones (inhibit, activin, follistatin): influence positive and negative feedback loops for the HPG axis • Adrenarche: increased production of adrenal androgens (DHA) prior to puberty – axillary and pubic hair growth, maturation of apocrine sweat glands (body odor), acne - “secondary sex characteristics” • Gonadarche: gonadal maturation Female reproductive organs: uterus and ovaries – NOT ON STUDY GUIDE • Uterus: hollow, pear-shaped organ o Fundus, corpus, isthmus, cervix o Layers: ▪ Perimetrium (parietal peritoneum): outer serous membrane that covers uterus ▪ Myometrium: thick, muscular middle layer; helps childbirth ▪ Endometrium: inner uterine lining • Ovaries: female gonads; primary reproductive organs osecrete hormones (progesterone, estrogen), develop and release female gametes (ova) oComponents: ▪ Medulla, cortex (ovarian follicles, theca cells, granulosa cells Ovulation and ovarian cycle • Release of an ovum; once every menstrual cycle usually only one of the follicles reaches maturation and discharges its ovum through the ovary’s outer covering • Ovarian cycle: continuous from puberty to menopause o After ejecting mature ovum, the follicle develops into the corpus luteum o If the ovum is fertilized then the corpus luteum enlarges and secretes hormones to support pregnancy o If ovum is not fertilized the corpus luteum secretes hormones (primarily progesterone) for 14 days then degenerates which triggers the maturation of another follicle • Gonadotropins and hormones regulate the ovarian function – any disorder that disrupts hormonal process can cause ovarian dysfunction and infertility o Ex: abnormal pituitary/thyroid function, benign or malignant growths, cysts, infection, inflammation Basics of menstrual cycle; phases and hormone role? LH causes what? Estrogen does what? • Menarche: first menstruation; menopause: cessation of flow; normal cycle = 28 days ▪ Levels of sex hormones decrease with the last menstrual cycle – reproductive organ atrophy, thinning of vaginal epithelium, decreased glandular secretions that are more alkaline (less protective) ▪ Continued sexual activity and orgasm reduce vaginal changes o Ovarian changes: ▪ Decrease around age 30, accelerates after age 60 ▪ 500,000 follicles present at puberty; 1000 at menopause o Uterine changes: thickness is greater – periods are heavier (menorrhagia) or spotting (metrorrhagia) o Breast tissue changes: size and firmness reduce o Urogenital tract changes: ▪ Ovaries shrink; uterus atrophies; vagina shortens, narrows, and loses elasticity ▪ Lubrication of vagina diminishes and vagina pH increases – higher incidence of vaginitis o Skeletal changes: brittleness and porosity increases; risk for osteoporosis and fracture increases o Cardiac changes: risk for coronary heart disease significantly increases o Other changes: skin dryness and wrinkling increases • Male: o Function diminishes with age but does not cease; longer capacity o Testes atrophy and produce less testosterone ▪ Some seminiferous tubules may degenerate and become fibrotic – affect libido and sperm morphology – sperm count is normal – semen contains more defective and nonmotile sperm o Erectile reflex is diminished and occurs more slowly as age advances (may also affect ejaculatory function) o Reduced testosterone levels cause some loss of function in the internal genitalia and hypertrophy of the prostate gland PATHOPHYSIOLOGY Delayed vs. precocious puberty • Delayed o Secondary sex characteristics have not yet appeared in girls by age 13; in boys by age 14 o 95% of cases are simply a physiologic delay – hormone levels normal, HPG axis intact, just slow ▪ Greater in boys and tends to be familial o 5% of cases are caused by a disruption of the HPG axis – chronic condition that delays bone aging such as celiac disease, anorexia, hypothyroidism ▪ LH and FSH regulated by secretion of GnRH by hypothalamus controls gonad function ▪ GPR54 receptor ID’d as gatekeeper gene for activation of the GnRH axis – keeps axis normal • Precocious o Sexual maturation before age 6 in black girls; age 7 in white girls; age 9 in boys – most common in girls o Forms: ▪ Complete: sex appropriate, onset of all pubertal features ▪ Mixed: not sex appropriate, virilization of a girl or feminization of a boy ▪ Partial: development of one secondary sex characteristic only, can be in combination o Central precocious puberty is GnRH dependent – HPG axis is working normally but prematurely o Typically caused by neoplasms that secrete hormones Primary and secondary dysmenorrhea • Dysmenorrhea patho: o Result of the effects of excess endometrial prostaglandin production and enhanced by progesterone o Prostaglandins are released during first 48 hours of menstruation when symptoms are most intense • Primary dysmenorrhea: o Painful menstruation associated with prostaglandin release in ovulatory cycles but not pelvic disease o Related to the duration and amount of menstrual flow • Secondary dysmenorrhea: o Painful menstruation related to pelvic pathology – can occur any time in the menstrual cycle Amenorrhea/ basic patho and definition. Primary vs. Secondary? • Amenorrhea: lack of menstruation – most common cause is pregnancy • Primary amenorrhea: o Absence of menstruation by age 14 without development of secondary sex characteristics and/or by age 16 regardless of the presence of secondary sex characteristics • Secondary amenorrhea: o Absence of menstruation for a time equivalent to three or more cycles or 6 months in women who have previously menstruated – associated with anovulation • Categories based on location where underlying disorder is occurring: o Compartment I: disorders of the outflow tract or uterus o Compartment II: disorders of the ovary o Compartment III: disorders of the anterior pituitary o Compartment IV: disorders of the CNS or hypothalamic factors DUB basic patho, definition • Dysfunctional uterine bleeding: heavy or irregular bleeding in the absence of disease o Perimenopausal women are most affected • Patho: 80% associated with anovulatory cycles o Hypomenorrhea followed by missed periods or prolonged intervals between menses can mark onset of physiologic perimenopause or may be early sign of pathologically premature ovulatory failure and secondary amenorrhea o DUB secondary to ovarian dysfunction is result of progesterone deficiency or estrogen excess o DUB in ovulatory cycles isn’t common – result of lesions or corpus luteum defects PCOS basic patho; what is associated with it (hyperandrogenic state; insulin intolerance, etc.) • Polycystic ovarian syndrome: oligo-ovulation or anovulation and elevated levels of androgens or clinical signs of hyperandrogenism and polycystic ovaries • Leading cause of infertility in the United States – result of prolonged anovulation • Hyperandrogenic state is cardinal feature – also common are glucose intolerance, insulin resistance (+obese), hyperinsulinemia which aggravate hyperandrogenic state and further symptoms • Results in infertility, menstrual bleeding disorders, hirsutism, acne, endometrial hyperplasia, CV disease, DM, and obesity •Patho: o High levels of insulin stimulates androgen secretion by the ovarian stroma and reduces hormone-binding globulin – net effect is increase in free testosterone levels ▪ Excess androgens affect follicular growth – insulin affects follicular decline by suppressing apoptosis – allows cells to survive when they’d normally die o Increased leptin levels cause increased release of GnRH and then affect entire axis – FSH low and LH levels increased – persistent LH elevation increases androgens – circulating androgens are converted to estrogen in the tissues which creates a positive feedback to LH and negative feedback to FSH ▪ Because there is a small amount of FSH there is new follicular growth but not to maturation – increased androgen secretion contributes to follicular failure and persistent lack of ovulation – new follicular cells and lack of apoptosis – enlarged, cystic ovaries (a symptom, not the cause) PMS symptoms which are more common, basic underlying patho? • Premenstrual syndrome: cyclic physical, psychological, or behavioral changes that impair interpersonal relationships or interfere with usual daily activities o Occurs in luteal phase of the menstrual cycle • Greater 200 physical, emotional, and behavioral signs and symptoms o Emotional: depression, anger, irritability, fatigue; *most distressing of the symptoms o Physical: water retention, bloating, weight gain (result of sex steroid interacting with RAAS) • Patho: o Abnormal tissue response to normal changes of the menstrual cycle – biologic response triggered by fluctuating estrogen and progesterone levels o Serotonin, GABA, and noradrenaline may have mediating roles on symptom manifestation PID what is it, basic patho, salpingitis, oophoritis? Manifestations • Pelvic inflammatory disease: acute inflammatory disease caused by infection – any organ of reproductive tract o Salpingitis: inflammation of the fallopian tubes o Oophoritis: inflammation of the ovaries o STI’s migrate from the vagina to the upper genital tract – chlamydia and gonorrhea most common • Patho: o Failure of numerous defense mechanisms – virulence of the organism, size of the inoculum, and defense status of the individual determine whether an infectious process result • Vaginal cancer o Arise from epithelium o Rare, most are secondary – risk factors are in-utero exposure to DES (non-steroidal estrogen) • Vulvar cancer o Most are squamous cell carcinoma; some melanomas, Bartholin gland carcinoma, sarcoma, and adenosquamous carcinoma – risk factor: HPV infection • Endometrial cancer o Most common pelvic region cancer o Risk factors: unopposed estrogen exposure, obesity, infertility, failure to ovulate, early menarche/ late menopause, tamoxifen - *oral contraceptive use protects against endometrial and ovarian cancers • Ovarian cancer o Cause of the most deaths of any other genital cancer in women o Risk factors: early menarche/late menopause, nulliparity, use of fertility drugs, and associations with breast cancer susceptibility genes Not on study guide: impaired fertility Urethritis in males • Urethritis: inflammation of the urethra – usually caused by a sexually transmitted infection o Nonsexual origins: urologic procedures, insertion of foreign objects, anatomic abnormalities, trauma • Symptoms: dysuria, frequency, urgency, urethral tingling or itching, and clear or purulent discharge Urethral stricture basics • Fibrotic narrowing of the urethra caused by scarring – acquired or congenital • Commonly a result of trauma or untreated or severe urethral infections • Symptoms: *diminished force and caliber of the urinary stream; urinary frequency and hesitancy, mild dysuria, double urine stream or spraying, post void dribbling Phimosis and paraphimosis differences, what causes • Phimosis: inability to retract foreskin over the glans of the penis (distal to proximal) o Caused by poor hygiene or chronic infections – can lead to paraphimosis • Paraphimosis: inability to replace or cover the glans with the foreskin (proximal to distal) o Can constrict the penile blood vessels, preventing circulation to the glans Peyronie disease and Priapism; what are they basic patho • Peyronie disease: “bent nail syndrome” o Slow development of fibrous plaques (thickening) in the erectile tissue of the corpus cavernosa – fibrosis prevents engorgement on the affected side – lateral curvature of the penis during erection o Occurs in middle-aged men and causes painful erections and intercourse • Priapism: condition of prolonged painful penile erection, not stimulated by sexual arousal o Urologic emergency o Corpus cavernosa fills with blood that does not drain out because of a venous obstruction o Associated with spinal cord trauma, sickle cell disease, leukemia, pelvic tumors; can be idiopathic Penile cancer and balanitis basics • Penile cancer o Rare; mostly squamous cell carcinomas ▪ Penile carcinoma in situ involves the glans; invasive carcinoma involves the glans and shaft o Risk factors: HPV, smoking, psoriasis treatment o 5-year survival rate is 50% • Balanitis: inflammation of the glans penis o Usually associated with foreskin inflammation (posthitis), phimosis, skin disorders, and infections o Accumulation under the foreskin (smegma) causes irritation of the glans Varicocele, hydrocele, Spermatocele basics what are they • Varicocele: o Inflammation/dilation of veins in the spermatic cord o Caused by inadequate or absent valves in the spermatic veins • Hydrocele: o Scrotal swelling caused by collection of fluid within the tunica vaginalis o Imbalance between fluid secretion and reabsorption • Spermatocele: o Painless diverticulum of the epididymis located between the head of the epididymis and the testes o Contains milky fluid that contains sperm and does not cover the entire anterior scrotal surface Cryptorchidism, Orchitis basics, what are they? Complications? • Cryptorchidism: o Congenital condition in which one or both testes fail to descend from abdominal cavity into scrotum o Treated or untreated is associated with infertility and increased risk of testicular cancer • Orchitis: o Acute inflammation of the testes o Complication of a systemic disease or related to epididymitis – mumps most common cause o Pathogenic organisms may reach the testes by ascending through the vas deferens and epididymis o Complications: hydrocele and atrophy Testicular cancer, torsion of the testes, basic patho and manifestations • Torsion of the testes o Rotation of the testes causing twisting of the blood vessels in the spermatic cord o Pain and swollen testes – may be spontaneous or follow physical exertion or trauma o Surgical emergency: needs to be corrected within 4-6 hours otherwise necrosis and atrophy occur • Testicular cancer o Among the most curable of cancers; common in men between age 15-35 o Causes painless testicular enlargement or nodules; most are germ cell tumors o Cause is unknown – may be high androgen levels, genetic predisposition, or a history or cryptorchidism, trauma, or infection Epididymitis basic patho and manifestation • Epididymitis: inflammation of the epididymis (coiled tube that connects vas deferens to rear of testicle) o Common in sexually active young men o Pathogenic microorganism reaches the epididymis by ascending the vas deferens from an already infected bladder or urethra BPH basic patho and manifestations, Prostatitis, types basic patho and manifestations, Cancer of prostate risk factors and manifestations • Benign prostatic hyperplasia: enlargement of the prostate gland o Symptoms associated with urethral compression – lower urinary tract symptoms ▪ Irritative: frequency, urgency, nocturia, urge incontinence ▪ Obstructive: hesitancy or difficulty initiating the stream, straining to void, a reduced flow, intermittent stream, or sensation of incomplete emptying o Relationship to aging o Complex pathophysiology: Circulating androgens (DHT) are associated with BPH and enlargement DHT is converted to testosterone by type II 5-alpha-reductase • DHT works locally, not systemically – prostate enlargement relies on DHT ▪ Growth promoting and tissue remodeling microenvironment supported – interactions lead to increase in prostate volume related to increased testosterone levels • Prostatitis: inflammation of the prostate o Normal protective barriers that protect the lower urogenital tract from infection: urethral length, micturition, ejaculation, antimicrobials in prostatic fluid (PAF=prostatic antibacterial factor *most important chemical defense*) ▪ Structural malformations and instrumentation weaken these defenses o Similar symptoms to UTI with acute; symptoms of BPH with chronic nonbacterial o Types: ▪ Acute bacterial: ascending infection of the urinary tract • Inflammatory response causes prostate to enlarge, become tender, and firm or boggy • Clinical manifestations: similar symptoms to acute cystitis or pyelonephritis; sudden onset of malaise, low back and perineal pain, high fever and chills, dysuria, inability to empty bladder, nocturia, urinary retention o Invasive breast carcinoma ▪ Malignant invasive epithelial lesion derived from the terminal duct lobular unit – can arise anywhere in the breast parenchyma or accessory breast tissue ▪ Most common in upper outer quadrant ▪ Clinical manifestations: first is usually a small, painless lump in the breast; palpable lymph nodes in the axilla, dimpling of the skin, nipple and skin retraction, nipple discharge, ulcerations, reddened skin, bone pain associated with bony mets • Male breast cancer o Most commonly seen after age 60 – generally uncommon but incidence is increasing o Tumors resemble carcinomas of the breast in women; most are ER+ o Clinical manifestations: crusting and nipple discharge o Risk factors: gynecomastia, radiation of the chest wall, germline mutations in BRCA 1 and BRCA 2, FH of breast cancer, Klinefelter syndrome, testicular disorders, obesity o Poor prognosis because of delay of treatment All basic patho and clinical manifestations of all STIs including stages of syphilis Bacterial • Gonorrhea o Patho: Microorganisms of the species Neisseria gonorrhoeae (aerobic, non-spore-forming, gram negative diplococcus – pili help attach to epithelial cells of mucous membranes) Can be local or systemic Complications: PID, sterility, disseminated infection; passed from mother to fetus as eye infection 1-12 days after birth Most common sites: endocervical canal (women); urethra or rectum (men) o Clinical manifestations: Men: sudden onset of painful urination or purulent penile discharge or both Women: asymptomatic; dysuria, increased discharge, increased flow or dysmenorrhea, dyspareunia, lower abdominal and/or pelvic pain; fever, mucopurulent discharge from cervos o *Disseminated gonococcal infection (DGI): rare systemic complication brought about by the spread of infection through the bloodstream ▪ Life threatening – generalized rash, severe joint pain, perihepatitis, ophthalmia neonatorum -Perihepatitis: spreads to liver - opthalmia neonatorum- newborn eye infection from mother • Syphilis o Patho: Caused by Treponema pallidum – works like a corkscrew to infect any body organ or tissue Transmitted most often during first few years of infection – higher incidence among male homosexual activity, poor urban areas, prison community Transmitted to fetus during pregnancy as early as 9 weeks gestation – contributes to prematurity, bone marrow depression, CNS involvement, renal failure, IUGR o Clinical manifestations: ▪ Becomes systemic shortly after infection ▪ Primary: 12 days-12 weeks after exposure (avg 3 weeks) • Granulomatous tissue reaction (hard, painless chancre at site of infection), firm enlarged and nontender regional lymph nodes accompany chancres, microorganisms drain with the lymphatic fluid ▪ Secondary: 6 weeks after appearance of hard chancre • Fever, malaise, sore throat, hoarseness, anorexia, joint pain, skin rash, lesions o Stages ▪ Latent (as short as one year or as long as a lifetime): medical evidence of the infection, asymptomatic individual ▪ Tertiary (appearing after latent phase): usually asymptomatic yet most severe stage • Destructive systemic manifestations: formation of gummas (destructive skin, bone, and soft-tissue lesions), CV alterations (aneurysms, heart valve insufficiencies, heart failure), CNS dysfunction (neurosyphilis) o Congenital: vasculitis, necrosis, fibrosis, distribution of Treponema pallidum throughout the tissues • Chancroid o Patho: ▪ Acute infectious disease caused by Haemophilus ducreyi (gram negative bacillus) o Clinical manifestations: ▪ Painful, tender, soft chancre ▪ Women: asymptomatic but can have dysuria, dyspareunia, vaginal discharge, pain on defecation, or rectal bleeding ▪ Men: unilateral, painful genital ulcers, local lymphadenopathy, inguinal buboes • Granuloma inguinale (donovanosis) o Patho: ▪ Chronic, progressive, destructive bacterial infection ▪ Klebsiella granulomatous – gram negative non-spore-forming encapsulated bacteria ▪ Mildly contagious – repeated exposure required – concurrent with syphilis is common ▪ Donovan bodies: bacteria-filled vacuoles within white cells o Clinical manifestations: ▪ Painful nodule with itching; ulcers on penis or labia • Bacterial vaginosis o Patho: ▪ Sexually associated but not always a STI ▪ Caused by Gardnerella vaginalis and other anaerobes o Clinical manifestations: ▪ Increased thin, grey-white, vaginal discharge with a strong fishy odor • Overgrowth of anaerobic bacteria produce aromatic •Chlamydia • Patho: Chlamydia trachomatis -Obligate, Gram-negative, intracellular bacterium -Metabolically active parasite -Localizes to epithelial tissue and can spread throughout the urogenital tract Causes: -**Most common STI in the United States -Untreated or undertreated chlamydial infections are the primary cause of preventable infertility and ectopic pregnancy -**Leading cause of blindness worldwide -Passes from infected mother to the eyes of newborn infants during birth • Manifestations: -Men: Clear, mucous discharge or mild burning with urination -Women: Leading cause of tubal infertility; acute urethral syndrome (dysuria, urinary frequency, and presence of sterile pus in the urine); yellow mucopurulent discharge with cervicitis -Newborn: Conjunctivitis and pneumonia Viral • HPV o Patho: Most common viral STI in the US Nonenveloped, circular, double stranded DNA virus Initial infection follows trauma to the epithelium that allows the virus to reach and infect the basal cells of the epithelium which are supportive to viral propagation – infected epithelial cells undergo transformation, proliferate, and form a warty growth Risk factors: multiple sexual partners, early onset of sexual activity (16-25 years of age) Associated with cervical and vulvar cancer in females and anorectal and squamous cell carcinoma of the penis in men; infants can be infected during delivery o Clinical manifestations: ▪ High risk strains or “hidden strains” (HR-HPV) do not cause genital warts – dangerous for spreading ▪ Condylomata acuminata (genital warts) - soft, skin-colored, whitish pink-to-reddish brown benign cauliflower painless growths • Genital herpes o Patho: ▪ Two serotypes: genital lesions can be caused by either • Herpes simplex virus type 1 and type 2 – clinically indistinguishable; most are type 2 ▪ Most common cause of genital ulceration in US – reaching epidemic status but underreported ▪ Neonatal infections can occur primarily intrapartum and postpartum