Virginia Commonwealth University: NURS 345- Exam 4 Study Guide; Complete A+ guide updated 2025.

Exam 4 Study Guide Total number of questions: Approximately 60 Total number of points: 100 Time limit: 90 minutes The exam is mostly multiple choice questions, but there are some newer format type questions. Partial credit will be awarded for the newer question format. The question format will be similar to exams 1–3. We will not be reusing questions from previous exams. However, questions may appear similar, so read each question carefully. The question topics are listed below. Note that these topics include both pathophysiology and pharmacology, and some questions cover more than one topic. This is a general guide and is not an allinclusive list. Exam Topics Digestive (approx. 10 questions) Gastritis:  Inflammatory disorder of the gastric mucosa  Common causes include medications such as NSAIDS (ibuprofen, naproxen, indomethacin, and aspirin)  A common cause of vitamin B12 deficiency (because gastritis impairs the usual mechanisms by which vitamin B12 is absorbed  Regular vitamin B12 absorption: o Hydrochloric acid in the stomach removes vitamin B12 from the food that was eaten o The vitamin B12 combines with intrinsic factor, which is a protein made by the stomach o If someone has gastritis, they are not going to be able to make intrinsic factor well o This allows vitamin B12 to then be absorbed in the small intestine (ileum) o Causes anemia which would be manifested by a low RBC count, low hematocrit, and low hemoglobin  Acute gastritis o Caused by injury of the protective mucosal barrier by drugs, chemicals, or H pylori infection  Chronic gastritis o Causes chronic inflammation, mucosal atrophy, and epithelial metaplasia o Tends to occur in older adults o Type A, immune (fundal) o Type B, nonimmune (antral) o Type AB: Types A and B (also known as pangastritis) o Type C: Associated with reflux of bile and pancreatic secretions into the stomach  Symptoms vague o Anorexia, fullness, nausea, vomiting, & epigastric pain, abdominal discomfort, bleeding o Healing typically occurs spontaneously within a few dayso It is recommended to discontinue injurious medications, to use antacids, or to decrease acid secretion with a histamine-2 receptor antagonist to facilitate healing o Symptoms can usually be managed by eating smaller meals in conjunction with a soft bland diet and by avoiding medications and chemicals that can further exacerbate the inflammation  Treatment o Antibiotics for H. pylori infection o Vitamin B12 is administered to correct pernicious anemia PUD: Peptic Ulcer Disease:  A break or ulceration in the protective mucosal lining of the lower esophagus, stomach, or duodenum  The ulcers develop when the mucosal protective factors are overcome by erosive factors commonly caused by NSAIDs and H pylori infection  Superficial o Erosions that erode the mucosa but do not penetrate the muscularis mucosae  Deep o True ulcers that extend through the muscularis mucosae  True ulcer o Extend through the muscularis mucosae and damaged blood vessels which causes hemorrhage and occasionally causes perforation of the GI wall (can cause peritonitis)  Zollinger-Ellison syndrome o Rare syndrome associated with peptic ulcers caused by gastrin-secreting neuroendocrine tumor or multiple tumors of the pancreas or duodenum  Protective factors o Mucus  Secreted cells of the GI mucosa  Forms a barrier to protect underlying cells from acid and pepsin o Bicarbonate  Secreted by epithelial cells of stomach and duodenum  Most remains trapped in mucus layer to neutralize hydrogen ions that penetrate the mucus o Blood flow  Poor blood flow can lead to ischemia, cell injury, and vulnerability to attack o Prostaglandins  Stimulate the secretion of mucus and bicarbonate  Duodenal ulcers o Most common o Causes  Helicobacter pylori infection  Use of NSAIDs o Characterized by intermittent pain in the epigastric area  Relieved rapidly by ingestion of food or antacids (pain-food-relief pattern) o Management aimed at relieving the causes and effects of hyperacidity and preventing complicationso Common complications include bleeding, perforation, as well as obstruction of the duodenum or the outlet of the stomach o Bleeding from duodenal ulcers causes hematemesis (blood in vomit) or melena (blood in the stool) o If someone experiences obstruction of the duodenum or the outlet of the stomach, it is usually due to edema from inflammation or from scarring from chronic injury o Often heal spontaneously but they will reoccur in months if the patient is not treated Duodenal Ulcers: Pathophysiology:  Causative factors cause acid and pepsin concentrations in the duodenum to increase and penetrate the mucosal barrier.  The increased duodenal acid promotes gastric metaplasia in the duodenum.  Both the H. pylori and increased acid result in decreased duodenal bicarbonate production.  The end result is ulceration.  H. pylori infection causes increased levels of gastrin resulting in increased stomach acid secretion and an increased acid load in the duodenum. o H. pylori also produces a toxin that causes loss of protective mucosal cells. o H. pylori infection activates immune cells and releases inflammatory cytokines which damage the mucosa.  NSAIDs o All NSAIDs inhibit COX, an enzyme o The COX enzyme has 2 forms: COX-1 and COX-2. o COX-1 is found in almost all tissues and is responsible for several protective physiologic functions. o COX-2 is made mainly at the sites of tissue injury, where it mediates inflammation o Inhibiting COX-1 causes many of the untoward effects of NSAIDs, including ulcers. o Non selective NSAIDs- Inhibit both COX-1 and COX-2 o People develop PUD from the inhibition of COX-1  Also causes many of the other adverse effects of NSAIDs Duodenal Ulcers: Management:  Treatment/eliminate of the underlying cause o H. pylori with antibiotics o NSAIDs  Antacids  H2 blockers or proton pump inhibitors  Surgical resection for severe complications o Bleeding, perforation, obstruction, peritonitis Gastric Ulcers:  Gastric ulcers tend to develop in the antral region of the stomach, adjacent to the acid-secreting mucosa of the body  The primary defect is an increased mucosal permeability to hydrogen ions  Gastric secretion tends to be normal or less than normal and there may be a decreased mass of parietal cells (parietal cells secrete gastric acid)  A break in the mucosal barrier always hydrogen ions to infuse into the mucosa where they disrupt permeability and cellular structure Manifestations and treatment similar to duodenal ulcers except food causes pain o People tend to eat less food which can result in weight loss and nutrition deficiencies  Bile salts help us break down fat  Can cause damage to the cells of the mucosal barrier Stress-Related Mucosal Disease:  Acute form of peptic ulcer that is related to severe illness or major trauma o Ischemic ulcers  Within hours of trauma, burns, hemorrhage, heart failure, or sepsis o Curling ulcers  Ulcers that develop as a result of burn injury o Cushing ulcers  Ulcers that develop as a result of a brain injury or brain surgery  The primary clinical manifestation of stress-related mucosal disease is bleeding Peptic Ulcer Disease: Treatment:  Medical management o Drugs do not alter the disease process, but they create conditions conducive to healing o Antibiotics o Antisecretory agents (proton pump inhibitors [PPIs], histamine2 receptor antagonists [H2RAs]) o Mucosal protectants o Antisecretory agents that enhance mucosal defenses o Antacids  Surgical management o Indicated for recurrent or uncontrolled bleeding and perforation of the stomach or duodenum Three Ways Antiulcer Drugs Work: Antibiotic Regimens:  Goal: Minimize emergence of resistance; guidelines recommend using at least two antibiotics, preferably three (Amoxicillin, Clarithromycin, Bismuth compounds, Tetracycline, Metronidazole, Tinidazole)  Antisecretory agent: PPI or histamine2 receptor antagonist (H2RA) also should be used Eradication rates are good with a 10-day course and slightly better with a 14-day course Antibiotics for PUD:  Clarithromycin [Biaxin] o Suppresses growth of H. pylori by inhibiting protein synthesis. o Common side effects: Nausea, diarrhea, and distortion of taste.  Amoxicillin o Kills bacteria by disrupting the cell wall. Antibacterial activity is highest at a neutral pH o Common side effect: diarrhea. Bismuth  Bismuth compounds (bismuth subsalicylate and bismuth subcitrate) act topically to disrupt the cell wall of H. pylori, thereby causing lysis and death. o Have anti-infective properties o Can cause a black discoloration to the tongue and the stool  Tetracycline o Inhibits bacterial protein synthesis o Because tetracycline can stain developing teeth, it should not be used by pregnant women or young children. Metronidazole  Metronidazole [Flagyl] o More than 40% of strains are now resistant o Common side effects: Nausea and headache. o A disulfiram-like reaction can occur if metronidazole is used with alcohol, and hence alcohol must be avoided; Can cause chest pain, dizziness, redness of the face, diaphoresis, N&V, headache, dyspnea, and fatigue o Metronidazole should not be taken during pregnancy.  Tinidazole [Tindamax] o Similar to metronidazole and shares that drug’s adverse effects and interactions. Histamine2-Receptor Antagonists:  Histamine acts through 2 types of receptors name H1 and H2  H1 receptors produce symptoms of allergy  H2 receptors are located on the parietal cells of the stomach, and they promote the secretion of gastric acid  Blocking the H2 receptors will decrease both the volume of gastric secretions and its acid concentration  First-choice drugs for treating gastric and duodenal ulcers  Suppress acid secretion by blocking H2 receptors on parietal cells  All are equally effective  Serious side effects are uncommon  Cimetidine [Tagamet] o Selective to the H2 receptors; Does not suppress allergy symptoms o Can cause gynecomastia, as well as reduced libido and erectile dysfunction  Famotidine [Pepcid]  Nizatidine [Axid] Cimetidine (Tagamet):  Pharmacokinetics o Absorption is slowed if taken with mealso Crosses the blood-brain barrier with difficulty o May cause some CNS side effects o Administer medication slowly and monitor the patient for complications  Therapeutic uses o Gastric and duodenal ulcers o Gastroesophageal reflux disease (GERD) o Zollinger-Ellison syndrome o Aspiration pneumonitis o Heartburn, acid indigestion, sour stomach  Adverse effects o Antiandrogenic effects o CNS effects o Pneumonia o IV bolus: Can cause hypotension and dysrhythmias  Drug interactions o Warfarin, phenytoin, theophylline, lidocaine o Cimetidine causes these drug levels to risk. If used, their dosages should be reduced. o Antacids can reduce absorption of cimetidine o Cimetidine and antacids should be administered at least 1 hour apart Other Antiulcer Drugs:  Sucralfate [Carafate]  Misoprostol [Cytotec]  Antacids Sucralfate (Carafate):  Creates a protective barrier for up to 6 hours  Should be taken on an empty stomach; 1 hr before or 2 hrs after meals  Adverse effects o Constipation (only 2% of patients)  Drug interactions o Antacids may interfere with effects of sucralfate; give at least 30 minutes apart o Sucralfate may impede the absorption of phenytoin, theophylline, digoxin, warfarin, and fluoroquinolone antibiotics o Administer sucralfate at least 2 hours apart Misoprostol (Cytotec):  An analog of prostaglandin E1  Therapeutic uses o Only approved GI indication is prevention of gastric ulcers caused by long-term NSAID therapy  Adverse effects o Most common: Dose-related diarrhea and abdominal pain o Contraindicated during pregnancy: Category X Antacids:  React with gastric acid to produce neutral salts or salts of low acidityo This reduces destruction of gut wall  Except for sodium bicarbonate, antacids do not alter systemic pH  4 major groups of antacids o Aluminum compounds  Aluminum hydroxide o Magnesium compounds  Magnesium hydroxide (milk of magnesia)  Magnesium oxide o Calcium compounds  Calcium carbonate (TUMS) o Sodium compounds  Sodium bicarbonate  Magaldrate (a complex of magnesium and aluminum compounds)  Adverse effects o Aluminum hydroxide and calcium carbonate--constipation o Magnesium hydroxide--diarrhea and magnesium toxicity o Sodium compounds—sodium loading  Avoid with HTN and HF  Drug interactions o Cimetidine o Sucralfate Pyloric obstruction  The blocking or narrowing of the opening between the stomach and the duodenum  Can be acquired or congenital o The acquired pyloric obstruction is caused by peptic ulcer disease or carcinoma near the pylorus o The ulceration causes obstruction resulting from inflammation, edema, spasm, or fibrosis (scarring) o Tumors cause obstruction by growing into the pylorus  Manifestations o Epigastric pain and fullness – becomes more distressing after eating and at the end of the day o Nausea – due to stomach muscle contractions in an attempt to force chyme past the obstruction o Succussion splash – sloshing sound caused by rolling or jarring of the abdomen o Vomiting – cardinal sign of obstruction o With a prolonged obstruction, malnutrition, dehydration, and extreme debilitation  Management o Nasogastric tube decompression o Proton pump inhibitors or H2-receptor antagonists o Fluid and electrolyte replacement (IV); Potassium imbalance is most common o Parenteral hyperalimentation (intravenous nutrition) o Pyloric stent placement o Surgical intervention Gastroparesis Delayed gastric emptying in the absence of mechanical gastric outlet obstruction  Associated with diabetes mellitus, surgical vagotomy, or fundoplication  Symptoms include nausea, vomiting, abdominal pain, and postprandial fullness or bloating  Treated with prokinetic medications Prokinetic Agents:  Metoclopramide [Reglan] o Suppresses emesis (by blocking receptors for dopamine and serotonin in the CTZ) o Increases upper GI motility (by enhancing the actions of acetylcholine)  Acts to increase peristalsis in the stomach and improves the amplitude of digestive contractions  Adverse effects o Sedation and diarrhea (with high doses). o Tardive dyskinesia (with long-term, high-dose therapy) ; Repetitive, involuntary movements of the arms, legs, and facial muscles  Contraindications o GI obstruction, perforation, or hemorrhage o Exposure to this medication during the first trimester of therapy is not associated with access risk of congenital malformations, but pregnant women should talk to their provider about continuing the medication Cholecystitis  Cholecystitis: Inflammation of the gallbladder or cystic duct Risk Factors:  Nonmodifiable o Middle age o Female sex (estrogen increases biliary cholesterol secretion) o Native American ancestry (related to a genetic predisposition that causes them to secrete high levels of cholesterol in the bile) o Genetic predisposition  Modifiable o Obesity (higher levels of cholesterol in bile) o Use of oral contraceptives (estrogen increases cholesterol production in the liver) (progesterone decreases gallbladder motility, leading to gallstones) o Rapid weight loss  Other o Gallbladder, pancreatic, or ileal disease Pathophysiology:  Gallstones are formed as a result of impaired metabolism of cholesterol, bilirubin, and bile acids. ; When these become imbalances, it leads to precipitation into stones  All gallstones contain cholesterol, unconjugated bilirubin, bilirubin calcium salts, fatty acids, calcium carbonates and phosphates, and mucin glycoproteins.  Decreased gallbladder motility may also contribute to gallstones. o The stones may lie dormant in the gallbladder or they may become lodged in the cystic or common bile duct, which would cause pain when the gallbladder contracts Cholesterol stones (70% cholesterol) o Most common type o Normally, bile contains enough chemicals to dissolve the cholesterol the liver excretes o If the liver excretes more cholesterol than bile can dissolve, the excess cholesterol may form into crystals and eventually stones o Cholesterol gallstones form in bile that is supersaturated with cholesterol o The bile secreted by the liver may be supersaturated with cholesterol (lithogenic bile) o Bile stasis can promote the progression of supersaturation and changes in the chemical composition of the bile (biliary sludge).  Other types of gallstones o Pigmented stones (black [hard] and brown [soft] with less than 30% cholesterol)  Pigmented brown stones are associated with biliary stasis, bacterial infections, and biliary parasites. These form from calcium bilirubinate and fatty acid soaps that bind with calcium.  Black gallstones are associated with chronic liver disease and hemolytic disease. They are composed of calcium bilirubinate with mucin glycoproteins. o Mixed stones  Cholecystitis o Acute or chronic o Causes  Gallstone becomes lodged in the cystic duct; The bile can continue to flow in the duodenum directly from the liver  Acalculous cholecystitis: Cholecystitis in the absence of obstruction; occurs most often in older adults and the critically-ill  Thought to be related to bile stasis and biliary sludge (viscous bile) o The gallbladder to become distended and inflamed o Inflammation may be confined to the mucous lining or involve the entire wall of the gallbladder. o Acute cholecystitis: The gallbladder is edematous and hyperemic and may be distended with bile or pus. o Chronic cholecystitis: The wall of the gallbladder becomes scarred after an acute attack. Decreased functioning occurs if large amounts of tissue become fibrotic. Clinical Manifestations:  Acute Cholecystitis o Pain is similar to that caused by gallstones. o Fever o Rebound tenderness o Abdominal muscle  Chronic Cholecystitis o Fat intolerance o Dyspepsia (indigestion) o Heartburn o Flatulence Laboratory Data:  Acute Cholecystitiso Leukocytosis  Elevated WBC count o Serum bilirubin and alkaline phosphatase levels may be elevated  May indicate blockage of the bile duct o Complete blood cell count, electrolytes, ALT, AST, ALP, bilirubin, albumin, calcium, serum amylase and lipase o Pregnancy test Alkaline Phosphatase:  Normal levels (don't memorize) o Adult: 30-120 units/L or 0.5-2.0 μ Kat/L o Elderly: slightly higher than adults o Child/adolescent:  < 2 years: 85-235 units/L  2-8 years: 65-210 units/L  9-15 years: 60-300 units/L  16-21 years: 30-200 units/L  ALP is found in many tissues o The highest concentrations are found in the liver, biliary tract epithelium, and bone.  Detection of this enzyme is important for determining liver and bone disorders  ALP levels are increased in obstructive biliary disease and cirrhosis Diagnostic Procedures:  Cholecystitis o Cholescintigraphy (HIDA scan)  A radiotracer scan of the gallbladder Disease Trajectory:  Once gallstones become symptomatic, a laparoscopic (or open) cholecystectomy (surgical removal of the gallbladder) is usually performed.  Other options o Bile acids (cholesterol solvents), such as ursodiol and chenodiol, are used to dissolve stones. Stones may recur. o ERCP with endoscopic sphincterotomy (papillotomy)  Endoscopic retrograde cholangiopancreatography (ERCP) o Extracorporeal shock-wave lithotripsy (ESWL)  Acute cholecystitis o Treatment focuses on pain control, control of infection with antibiotics, and maintaining fluid and electrolyte balance o If nausea and vomiting are severe, NG tube insertion and gastric decompression may be used to prevent further gallbladder stimulation. o Opioids are given for pain management. o Anticholinergics (antispasmodics) can decrease GI secretions and counteract smooth muscle spasms.  Chronic cholecystitis o Fat-soluble vitamin (A, D, E, and K) replacement may be neededo Bile acids, such as ursodiol and chenodiol, can help with digestion and vitamin absorption o Cholestyramine, bile acid sequestrant, may provide relief from itching (excess bile products may accumulate under the skin); Inhibits hepatic reuptake of the intestinal bile salts, which increase their loss in the stool Pancreatitis Intro:  Pancreatitis is inflammation of the pancreas  Relatively rare, can be life-threatening  Acute or chronic Acute Pancreatitis:  Most common cause o Obstruction to the outflow of pancreatic digestive enzymes caused by bile or pancreatic duct obstruction.  Other causes o Direct cellular injury from alcohol, drugs (e.g., NSAIDs), or viral infection  Chronic alcohol use is second most common cause  Mild pancreatitis (edematous or interstitial pancreatitis)  Severe pancreatitis o Increased risk of necrotizing acute pancreatitis, which is inflammation associated with pancreatic tissue necrosis o Increased risk of organ failure and sepsis o Almost half will have permanent decreases in pancreatic endocrine and exocrine function Pathophysiology of Acute pancreatitis:  If duct obstruction is present, there will be edema, impaired blood flow, and ischemia due to a backup of pancreatic secretions OR  Direct injury to the acinar cells can occur from alcohol, drugs, or viruses. o For example, the generation of toxic metabolites from alcohol metabolism injure pancreatic acinar cells  Both of these mechanisms lead to pancreatic enzymes release and activation o This can cause cellular injury, proteolysis (protein breakdown), edema, thrombosis (clot formation), hemorrhage, and necrosis AND o Inflammation, release of cytokines, and activation of complement  This process can cause many complications o Translocation of intestinal bacteria to the bloodstream may cause peritonitis or sepsis o Abscess and formation of pseudocysts (walled-off collections of pancreatic secretions)  Abscesses may rupture or perforate into adjacent organs  Systemic effects related to inflammation and the development of vasodilation, hypotension, shock, and other complications  Recurrent inflammation can cause pancreatic fibrosis, strictures, and duct obstruction that lead to chronic pancreatitisClinical manifestations:  Main manifestation: Abdominal pain due to distention of the pancreas, peritoneal irritation, and biliary tract obstruction. o Sudden onset of LUQ or mid-epigastric pain o Pain often radiates to the back o Pain is severe, deep, piercing, and continuous or steady o Eating worsens the pain o Pain commonly starts when the patient is recumbent (lying down)  Other manifestations o Low grade fever o GI: N/V, jaundice, abdominal tenderness with muscle guarding, diminished or absent bowel sounds, abdominal distention o CV: Hypotension, tachycardia, shock, hypovolemia  Due to plasma volume that is lost as inflammatory mediators are released into the circulation  Shock may occur from bleeding in the pancreas  Toxemia may occur from the activated pancreatic enzymes, or from hypovolemia due to fluid shifting into the retroperitoneal space o Lungs: Crackles; Due to the presence of fluid shifts o Skin  Areas of cyanosis or greenish to yellow-brown discoloration of the abdominal wall  Grey Turner spots or sign, a bluish flank discoloration  Cullen sign, a bluish periumbilical discoloration Laboratory Data:  Serum amylase and lipase o Serum amylase level is usually high early and stays high for 24 to 72 hours. o Serum lipase level is high in acute pancreatitis  Elevated liver enzymes (AST, ALT)  Hyperbilirubinemia; Obstructed biliary tract  Elevated triglycerides; Due to breakdown of triglycerides into toxic fatty acids that damage the pancreas  Hyperglycemia; Can occur if glucagon is released from damaged pancreatic alpha cells  Hypocalcemia; Can occur when calcium is deposited into areas of necrosis  Leukocytosis; Occurs due to the inflammatory process Other Diagnostic Tests:  Abdominal ultrasound, x-ray, or contrast-enhanced CT scan may identify pancreatic problems. o CT scan is the best imaging test for pancreatitis and complications, such as pseudocysts and abscesses  Chest x-rays may show atelectasis and pleural effusions. Disease Trajectory:  Most fully recover  For some, acute pancreatitis is fatal Some develop chronic pancreatitis Treatment:  Pain management  NPO o May need NG tube to suction  IV fluids o Usually isotonic o Severe cases: Albumin  Severe cases: Jejunal tube feeding  H2-receptor antagonists to decrease stimulation of pancreas by secretin  Antibiotics if infection is present Chronic Pancreatitis:  Progressive fibrotic destruction of the pancreas.  Chronic alcohol abuse is the most common cause.  Continuous or intermittent abdominal pain and weight loss are common.  Manifestations of pancreatic enzyme deficiency, such as steatorrhea or a malabsorption syndrome, are present in late stages of chronic pancreatitis. o Oral enzyme replacements are taken before and during meals.  Loss of islet cells can cause insulin-dependent diabetes and requires treatment.  Endoscopic or surgical drainage of cysts or partial resection of the pancreas may be required to relieve pain and to prevent cystic rupture. Complications of liver disorders (ascites, esophageal varices, hepatic encephalopathy) Ascites:  Ascites is the accumulation of fluid in the peritoneal cavity o Traps body fluid in the peritoneal space (it gets trapped) o This reduces the amount of body fluid available o Cirrhosis is the most common cause of ascites  May occur in right side heart failure, cancer, and malnutrition  Major mechanisms o Portal hypertension o Hypoalbuminemia o Hyperaldosteronism Pathophysiology:  Mechanism #1: Portal Hypertension o Portal hypertension causes increased resistance of blood flow through liver o This leads to an increased capillary filtration pressure o This causes proteins to shift from the blood vessels into the lymph space o When the lymphatic system is unable to carry off the excess proteins and water, they leak into the peritoneal cavity o The osmotic pressure of the proteins then draws more fluid into the peritoneal cavity  Mechanism #2: Hypoalbuminemia o Hepatocyte failure leads to decreased albumin synthesis o This decreases the capillary oncotic pressure This leads to the leakage of plasma out of the vascular space into the peritoneal cavity, leading to ascites  This also leads to decreased plasma volume, causing activation of the RAAS system and ADH secretion, further contributing to ascites  Mechanism #3: Hyperaldosteronism o Hepatocytes are damaged, leading to decreased liver catabolism (breakdown) of circulating aldosterone o This leads to activation of the RAAS system (end product is more aldosterone) and ADH secretion o This leads increased renal reabsorption of sodium and water, causing ascites Clinical Manifestations:  Ascites is manifested by abdominal distention with weight gain  Severe cases: Increase in abdominal pressure from the fluid accumulation may cause eversion of the umbilicus  Abdominal striae with distended abdominal wall veins may be present  Patients may have signs of dehydration and a decrease in urine output Laboratory Data and Diagnostic Procedures:  Hypokalemia is common o Due to hyperaldosteronism and diuretic therapy used to treat the ascites  Paracentesis is used to aspirate ascitic fluid for bacterial culture, biochemical analysis, and microscopic examination  The diagnosis is usually based on clinical manifestations and identification of liver disease Disease Trajectory:  Poor prognosis; liver transplant is best option  Complications o Pleural effusion  Fluid in lungs o Spontaneous bacterial peritonitis (SBP)  Bacterial infection of the acidic fluid  Needs to be treated with antibiotics Treatment:  Dietary salt restriction (where sodium goes, water goes)  Diuretics  Paracentesis- Aspirates acidic fluid from the peritoneal space  Electrolyte monitoring (Sodium and potassium)  Transjugular intrahepatic portosystemic shunt (TIPS) Portal hypertension:  Normal portal pressure is normally 3 mm Hg  Portal hypertension is an increase to a minimum of 10 mm Hg. o High blood pressure in the portal venous system is caused by resistance to blood flowPathophysiology:  Normally, the portal circulatory system brings blood to the liver from the stomach, intestines, spleen, and pancreas  Liver inflammation leads to liver necrosis  Liver necrosis leads to liver fibrosis and scarring  The fibrosis and scarring causes resistance to blood flow, resulting in portal hypertension o To reduce pressure, the body develops alternate circulatory pathways, (collateral circulation) o This leads to the development of esophageal and gastric varices and hemorrhoids  Very fragile and prone to bleeding Clinical Manifestations:  Vomiting of blood (hematemesis) from bleeding esophageal varices (most common)  Hemorrhoidal varices present as hematochezia and copious rectal bleeding o Can cause hematochezia, which is fresh blood that is passed through the anus Diagnostic Procedures:  Confirmed by upper GI endoscopy at the time of bleeding  Evaluation of portal venous pressure (rarely performed)  Imaging and blood tests Treatment:  Emergency management of bleeding varices includes o Sclerotherapy (involves injecting a sclerosing solution to the varices through a needle placed through the endoscope) or variceal ligation (performed during endoscopic procedure) o Compression of the varices with an inflatable tube or balloon  Surgical construction of transjugular intrahepatic portosystemic shunts (TIPS) and anastomosis of the portal vein to the inferior vena cava may decompress the varices. o Increases risk of hepatic encephalopathy o Allows blood flowing into the liver from the portal vein to flow through the stent directly into the hepatic vein o The hepatic vein drains blood out of the liver to the vena cava and then immediately to the heart  Liver transplantation is the most successful option for liver failure. Medications:  Emergency management of bleeding varices includes drugs that produce vasoconstriction of the splanchnic arterial bed, decrease portal blood flow, and decrease portal hypertension o Somatostatin analog octreotide (Sandostatin) or vasopressin  Nonselective β-blockers given to↓ Portal venous pressure and esophageal variceal bleeding o Nadolol [Inderal] o Propranolol [Corgard]  Keep and eye on BP and HR Hepatic Encephalopathy:  Also called portal system encephalopathy A complex neurologic syndrome characterized by impaired behavioral, cognitive, and motor function  Process o Liver necrosis leads to liver failure o Liver failure leads to hepatic encephalopathy (HE) o HE can lead to coma and death Pathophysiology:  Review: A major source of ammonia is the bacterial and enzymatic deamination of amino acids in the intestines. The ammonia that results from deamination normally goes to the liver via the portal circulation where it is converted to urea. The kidneys then excrete urea. o Ammonia is also produced by intestinal bacteria  Liver dysfunction and the development of collateral vessels that shunt blood around the liver to the systemic circulation permit toxins absorbed from the GI tract and normally removed by the liver, to accumulate and circulate freely to the brain.  The accumulated toxins alter cerebral energy metabolism, interfere with neurotransmission, and cause edema Risk Factors:  HE can also occur after placement of a transjugular intrahepatic portosystemic shunt (TIPS).  Avoid all CNS depressants as much as possible in pts with cirrhosis who have HE Clinical Manifestations:  Initial o Subtle personality changes o Memory loss o Irritability o Disinhibition o Lethargy o Sleep disturbances  Later o Confusion o Disorientation to time and space o Flapping tremor of the hands (asterixis) o Slow speech o Bradykinesia (slowed movements) o Stupor o Convulsions o Coma Laboratory Data:  Serum ammonia level o Adult: 10-80 mcg/dL o Child: 40-80 mcg/dL o Newborn: 90-150 mcg/dL Treatment: Correct fluid and electrolyte imbalances  Avoid drugs that cause CNS depression  Lactulose prevents ammonia absorption in the colon  Rifaximin decreases intestinal production of ammonia Musculoskeletal (approx. 7 questions) OA Osteoarthritis:  Characterized by o Loss and damage of articular cartilage o Inflammation o New bone formation of joint margins o Subchondral bone changes o Variable degrees of mild synovitis o Thickening of the joint capsule  Prevalence increases with age Pathophysiology:  The primary defect in OA is loss of articular cartilage  The chondrocytes of the articular cartilage become damaged early in the disease process due to o Atypical load bearing o Genetic, epigenetic, and biochemical factors OA: Process:  The articular cartilage surface flakes off and longitudinal fissures develop.  The cartilage becomes thin or absent.  As the articular cartilage erodes, cartilage-coated osteophytes (outgrowths of bone) grow outward from the underlying bone.  Joint mice (small pieces of osteophytes) break off into the synovial cavity, causing irritation, synovitis (inflammation of the synovial membrane), and joint effusion.  The joint capsule also becomes thickened and adheres to the underlying bone, limiting range of motion.  Destruction of articular cartilage begins in the matrix  Proteoglycan changes disrupt the pumping action that regulates movement of water and synovial fluid into and out of the cartilage.  Disruptions in cellular signaling pathways play a significant role in the development of OA.  Cytokines (i.e., interleukin-1 (IL-1) and TNF) may play a major role in cartilage degradation.  Cell-signaling proteins contribute to collagen breakdown in cartilage.  Collagen breakdown destroys the fibrils that give articular cartilage its tensile strength and exposes the chondrocytes to mechanical stress and enzyme attack.  When articular cartilage is damaged, abnormal subchondral bone remodeling occurs.  A cycle of destruction begins that involves all the components of a joint. Early OA Changes:  Destruction of articular cartilage and narrowing of the joint space.  There is inflammation and thickening of the joint capsule and synoviumLate OA Changes:  Constant friction of the two bone surfaces causes thickening of subarticular bone.  Osteophytes form around the periphery of the joint by irregular overgrowths of bone. Risk Factors:  Increased age  Joint trauma, long-term mechanical stress  Obesity Clinical Manifestations:  Pain (worsens with activity and improves with rest)  Stiffness (diminishes with activity) o Usually no more than 30 minutes  Enlargement of the joint o Heberden (DIP joints) o Bouchard nodes (PIP joints)  Tenderness  Limited motion  Muscle wasting  Partial dislocation  Deformity Laboratory Data:  No laboratory tests or biomarkers can be used to diagnose OA.  The erythrocyte sedimentation rate (ESR) is normal except for slight increases during acute inflammation.  Synovial fluid analysis o Normal viscosity o Clear yellow o Few cells Diagnostic Procedures:  X-rays  Early joint changes can be detected with bone scan, CT scan, or MRI Disease Trajectory: Conservative treatment o Exercise and weight loss o Pharmacologic therapies  Topical and oral NSAIDs o Intraarticular injections  Corticosteroids  Hyaluronic acid o Nutritional supplements  Chondroitin and glucosamine  Surgical treatment o Used to improve joint movement, correct deformity or malalignment, or create a new joint with artificial implants First Generation NSAIDS:  Exemplar drug: Ibuprofen [Advil, Motrin]  Mechanism of action: Inhibits COX-1 and COX-2 and has anti inflammatory, analgesic, and antipyretic actions. o COX-1 is found in almost all tissues and is responsible for several protective physiologic functions.  Inhibiting COX-1 causes many of the untoward effects of NSAIDs, including ulcers, bleeding, and renal impairment o COX-2 is made mainly at the sites of tissue injury, where it mediates inflammation.  Inhibition of COX-2 reduces inflammation, pain, and fever.  Inhibition of COX-2 is thought to increase the risk of MI, stroke, and renal impairment o Therapeutic uses: Fever, mild to moderate pain, and arthritis  Side effects: Generally well tolerated o Epigastric pain, heartburn, nausea, constipation, rash, dizziness, edema  Contraindications/precautions o Risk of gastric bleeding o Risk of MI and stroke o Stevens-Johnson syndrome (SJS), a severe hypersensitivity reaction that causes blistering of the skin and mucous membranes o Patients who are hypersensitive to aspirin are likely to experience cross-hypersensitivity with other NSAIDs  Interactions o Aspirin and ibuprofen: Increased bleeding risk o Lithium and ibuprofen: May increase lithium levels. o Selective serotonin reuptake inhibitors (SSRIs) and ibuprofen: SSRIs can inhibit platelet function, increased risk of gastrointestinal bleeding.  Medication administration o Give with food or 8-12 ounces of water to avoid GI effects  Evaluation of effectiveness: Monitor pain level Second Generation NSAIDS:  Exemplar drug: Celecoxib [Celebrex] Mechanism of action: Causes selective inhibition of COX-2, Therapeutic uses: Fever, mild to moderate pain, and arthritis  Side effects: Generally well tolerated o Dyspepsia and abdominal pain  Contraindications/precautions o Long-term reduction in GI complications is questionable o Increases risk of MI and stroke o Celecoxib contains a sulfur molecule that can precipitate an allergic reaction in patients allergic to sulfonamides.  Interactions o Celecoxib may increase the anticoagulant effects of warfarin and may thereby increase the risk for bleeding. o Celecoxib may decrease the diuretic effects of furosemide and the antihypertensive effects of ACE inhibitors. o Celecoxib may increase levels of lithium. o Levels of celecoxib may be increased by fluconazole.  Medication administration: May be taken with or without food.  Evaluation of effectiveness: Monitor pain level RA Rheumatoid Arthritis (RA):  Inflammatory autoimmune joint disease  Systemic autoimmune damage to connective tissue, primarily in the joints (synovial membrane)  Similar symptoms to osteoarthritis with some notable differences  Cause unknown; multifactorial with strong genetic predisposition Pathophysiology:  The antigen triggers an immune response in a genetically susceptible person.  With continued exposure to the antigen, normal antibodies (immunoglobulins) become autoantibodies—antibodies that attack host tissues (self-antigens) o These altered antibodies are called rheumatoid factors (RFs); abnormal IgG and IgM.  The antigen triggers an immune response in a genetically susceptible person.  T cells coordinate the immune response. o Cytokines are released o T cells interact with fibroblasts, converting synovium into a thick, abnormal layer of granulation tissue known as pannus. o Enzymes are released which cause joint destruction  T cells also express RANKL, which promotes osteoclast formation and causes bony erosion.  T cells also activate B lymphocytes  B lymphocytes are stimulated to produce more RFs  RFs bind with their target self-antigens in blood and synovial membrane, forming immune complexes  Formation of immune complexes leads to the activation of complement and an inflammatory response. o Complement makes the immune complex susceptible to phagocytosis  Results in joint injury leading pannus, joint destruction, fibrosis, and ankylosis (stiffness)Risk Factors:  Women  30-60 years old Clinical Manifestations:  Insidious onset  Systemic manifestations o Inflammation, fever, fatigue, weakness, anorexia, weight loss, and generalized aching and stiffness  Painful, tender, stiff joints o Initially the joints most commonly involved are the metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and wrists, with later involvement of larger weight bearing joints.  Joint deformities  Gel Phenomenon: Moderate to severe morning stiffness lasting 60 minutes or more  Spongy, soft feeling in joints  Rheumatoid nodules o A collection of inflammatory cells in the subcutaneous tissue o Can invade the skin, cardiac valves, pericardium, pleura, lung parenchyma, and spleen. RA Joint Deformities: Laboratory Data:  Erythrocyte sedimentation rate (ESR) o ESR is a measurement of the rate with which the RBCs settle in saline or plasma. o Inflammation increases the protein (mainly fibrinogen) content of plasma o This causes RBCs to stack up on one another, increasing their weight and causing them to descend faster. o Nonspecific test, only indicates inflammatory process.  Rheumatoid factor (RF)o Altered IgG and IgM antibodies o Approximately 80% of patients with RA have positive RF titers.  Antinuclear antibody (ANA) o Antinuclear antibodies attack a person’s own cells. o An increase in antinuclear antibody (ANA) titers is an indicator of autoimmune reaction.  C-reactive protein (CRP) o CRP is a protein produced primarily by the liver during an acute inflammatory process o Nonspecific; a positive test result indicates the presence of an infectious or inflammatory disorder. Diagnostic Procedures:  X-ray of involved joints  Synovial fluid analysis o Slightly cloudy, straw-colored o Fluid contains fibrin flecks o The enzyme MMP-3 is increased in the synovial fluid (marker of inflammation) o WBC count of synovial fluid is increased o Tissue biopsy can confirm inflammatory changes Disease Trajectory:  Early initiation of drug therapy improves outcomes  RA is typically marked by periods of remission and exacerbation  Physical and occupational therapy  Therapeutic exercise  Use of assistive devices  Surgery is used to treat deformities or mechanical deficiencies of joints Medications:  Nonsteroidal antiinflammatory drugs (NSAIDs) o Provide rapid relief of symptoms but do not prevent joint damage and do not slow disease progression  Glucocorticoids o Provide rapid relief of symptoms and can slow disease progression. o Use is limited to short-term use of exacerbations due to adverse effects (e.g., osteoporosis, gastric ulceration, adrenal suppression)  Disease-modifying antirheumatic drugs (DMARDs) o Reduce joint destruction and slow disease progression o 3 categories, conventional (traditional) DMARDs, biologic DMARDs, and targeted DMARDs Conventional (Traditional) DMARDs:  Exemplar drug: Methotrexate  Mechanism of action o Methotrexate is a folate antagonist. Folate is necessary for DNA synthesis and cellular replication, so Methotrexate inhibits these processes.  Therapeutic uses o RA, severe psoriasis, acute lymphoblastic leukemia Adverse effects o Hepatic fibrosis, bone marrow suppression, GI ulceration, and pneumonitis.  Contraindications/precautions o Contraindicated for patients with blood dyscrasias, immunodeficiency, and liver disease o Contraindicated in pregnancy o Periodic tests of liver and kidney function and complete blood cell counts are needed o Vaccines are less effective; live vaccines are contraindicated o Dosing with folic acid is recommended to reduce GI and hepatic toxicity  Interactions o Methotrexate and alcohol: Increased risk of hepatoxicity o Methotrexate and other drugs that decrease bone marrow function: Increased risk of myelosuppression  Medication administration: Oral, subq, IM o Oral: May take with or without food  Evaluation of effectiveness: Therapeutic effects may develop in 3 – 6 weeks Biologic DMARDs:  Tumor Necrosis Factor Antagonists  Exemplar drug: Etanercept [Enbrel]  Mechanism of action: Work by antagonizing the actions of TNF, an important immune mediator of joint injury in RA.  Etanercept binds with TNF and prevents TNF from interacting with its natural receptors on cells.  Therapeutic uses: RA, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis.  Adverse effects o Infections, neutropenia, injection site reactions o Headache, rhinitis, dizziness, cough, and abdominal pain  Contraindications/precautions o Risk of heart failure, acute liver failure, lymphoma, and other malignancies o Hematologic disorders: Neutropenia, thrombocytopenia, and aplastic anemia  Medication administration: Subq  Evaluation of effectiveness o Starts working in 1 – 2 weeks, but full effect may take 3 – 6 months Targeted DMARDs:  Janus Kinase Inhibitors  Exemplar drug: Tofacitinib [Xeljanz, Xeljanz XR]  Mechanism of action o JAKs are intracellular enzymes that have a role in initiating cytokine signaling as part of the signal transducer and activation of transcription (STAT) pathway. o This pathway is involved in inflammatory and immune responses o By inhibiting JAKs, they reduce immune and inflammatory responses that underlie the pathology of RA.  Therapeutic uses o RA, psoriatic arthritis and ulcerative colitis  Adverse effects o Infection, bone marrow suppressiono Headache, increased serum cholesterol, increased creatine phosphokinase, and skin rashes  Contraindications/precautions o Decreases efficacy of inactivated vaccines o Live vaccines should be avoided  Interactions o Biologic DMARDs and tofacitinib: Increased risk of toxicity o Tofacitinib and other immunosuppressants: Increased immunosuppressive effects  Medication administration o Oral, subq, IM o Oral: May take with or without food  Evaluation of effectiveness o Starts working in 2 weeks, but full effect may take 3 – 4 months Gout o Inflammatory response to excessive quantities of uric acid o Blood (hyperuricemia) o Other body fluids, including synovial fluid o Elevated levels lead to formation of monosodium urate crystals in joints o Cause acute, painful inflammation o Joint damage: gouty arthritis o Crystals under subcutaneous tissues o Tophi o Acute attacks are treated with anti-inflammatory medications (colchicine or prednisone) and NSAIDs or opioids for pain o Prevention of future attacks with medications to decrease the serum uric acid level o Xanthine oxidase inhibitor, allopurinol Osteoporosis Osteoporosis:  Old bone is resorbed faster than new bone is being formed in osteoporosis, causing the bones to lose density, becoming thinner and more porous. o Increases fracture risk, even with minor injury  The World Health Organization (WHO) definition o “A systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility.”  As bones become more fragile, falls of bumps that would not have normally caused a fracture previously would now cause the bone to break (AKA pathological fracture) o Most common sites are the spine, femoral neck, and wrist Pathophysiology: The OPG/RANKL/RANK System:  Cytokine receptor activator of nuclear factor κB ligand (RANKL) o A cytokine expressed by stromal cells and osteoblasts  RANKL stimulates several processes o RANKL stimulates RANK (Receptor activator nuclear factor κB) on osteoclast precursor cells and mature osteoclasts.o RANKL also stimulates intracellular pathways to promote osteoclast differentiation and activation o RANKL stimulates the PKB/Akt pathway (cytoskeletal reorganization and survival)  Increases resorption and bone loss  Osteoprotegerin (OPG) is secreted by stromal cells and osteoblasts o Acts as a “decoy” receptor and blocks RANK OPG/RANK/RANKL:  RANKL expression ultimately increases bone resorption and bone loss  OPG production blocks the effects of RANK, meaning it prevents bone resorption and bone loss Common Causes of Osteoporosis:  Glucocorticoid-induced osteoporosis (e.g., prednisone) o The most common type of secondary osteoporosis. o Glucocorticoids improve osteoclast survival, inhibit osteoblast formation and function, and increase osteocyte apoptosis (programmed cell death). o Glucocorticoids increase RANKL expression and inhibit OPG production by osteoblasts  Resulting in decreased thickness of the bone cortex and fewer, thinner, and more widely spaced trabeculae in the marrow. Age-Related Bone Loss:  Cause is unclear  What is known o Decreased serum growth hormone (GH) and IGF-1 levels, along with increased binding of RANKL and decreased OPG production, affect osteoblast and osteoclast function. o Loss of trabecular bone in men proceeds in a linear fashion with thinning of trabecular bone.  Women tend to have complete bone loss o Men have approximately 30% greater bone mass than women.  Men’s sex hormone levels decrease more gradually, so they maintain their bone mass longer than women. o Reduced physical activity in older persons probably contributes to age-related bone loss. Risk Factors:  Genetic o Family history of osteoporosis o White race o Greater age o Female sex  Anthropometric o Small stature o Fair or pale skinned o Thin build o Low bone mineral density  Hormonal and Metabolic o Early menopause (natural or surgical) o Late menarcheo Nulliparity o Obesity o Hypogonadism o Gaucher disease o Cushing syndrome o Weight below healthy range o Acidosis  Concurrent o Hyperparathyroidism  Illness and Trauma o Renal insufficiency, hypocalciuria o Rheumatoid arthritis o Spinal cord injury o Systemic lupus erythematosus  Liver Disease o Marrow disease (myeloma, mastocytosis, thalassemia)  Dietary o Low dietary calcium and vitamin D o Low endogenous magnesium o Excessive or low protein o Excessive sodium intake o Anorexia o Malabsorption  Lifestyle o Sedentary o Smoker o Alcohol consumption (excessive) o Low-impact fractures as an adult o Inability to rise from a chair without using one's arms  Drugs o Glucocorticoids Prednisone o Phenytoin [Dilantin] o Gonadotropin-releasing hormone agonists o Loop diuretics (e.g., furosemide [Lasix]) o Methotrexate o Thyroid medications o Heparin o Cyclosporin o Medroxyprogesterone acetate [Depo-Provera] o Retinoids Clinical Manifestations:  Common locations o Spine, hips, wrists  Pain  Bone deformity  FracturesLaboratory Data:  Serum calcium, phosphorus, and alkaline phosphatase (ALP) are usually normal  Biochemical markers of bone turnover  ALP may be increased after a fracture o Although ALP is found in many tissues, the highest concentrations are found in the liver, biliary tract epithelium, and bone. o Bone is the most frequent extrahepatic source of ALP o New bone growth and healing fractures are associated with elevated ALP levels Diagnostic Procedures:  Dual x-ray absorptiometry (DXA) o Gold standard for detecting and monitoring osteoporosis  Bone density is non indicative of bone quality o Measures bone mineral density (BMD) by passing a high and low energy x-ray beam through the body, usually in the hip and the spine. o The utility of DXA in predicting fracture risk has recently been enhanced by the development of a trabecular bone score (TBS) DXA Scan Interpretation:  BMD test results are compared with the ideal or peak BMD of a healthy 30-year-old adult and reported as T-scores.  A T-score of 0 means the BMD is equal to the norm for a healthy young adult.  Differences between the BMD and that of the healthy young adult norm are measured in units called standard deviations (SDs).  The greater the negative number, the lower the BMD and the higher the risk for fracture.  Sometimes a Z-score instead of a T-score. o The patient is compared with someone their own age, gender, and/or ethnic group instead of a healthy 30-year-old person. o Among older adults, Z-scores can be misleading because decreased bone density is common. o If the Z-score is −2 or lower, it may suggest that something other than aging is causing abnormal bone loss. T-Scores:Disease Trajectory:  Chronic disease  Management focuses on nutrition, calcium and vitamin D supplementation, exercise, prevention of falls and fractures, and drugs  Fracture is major complication Other Metabolic Bone Diseases:  Osteomalacia o Inadequate or delayed mineralization of osteoid o Remodeling cycle proceeds through osteoid formation but calcification does not occur; the result is soft bones  Pain, bone fractures, vertebral collapse, bone malformation o Results from vitamin D deficiency o Treatment varies by etiology  Paget Disease of the Bone o Also called osteitis deformans o Chronic accelerated remodeling of spongy bone and deposition of disorganized bone  Enlarges and softens affected bones  Mostly affects vertebrae, skull, sacrum, sternum, pelvis, and femur o Often symptomless o Genetic and environmental factors o Evaluation based on radiographic findings Fractures Types of Fractures:  Complete o Bone completely separated by a break into two parts  Incomplete o Partial break in the bone but still in one piece  Open (formerly compound) o Bone is exposed to air through a break in the skin  Closed (formerly simple or incomplete)o Skin is closed  Displaced o The 2 ends of the broken bone are separated from each other and out of their normal positions  Nondisplaced o The bone fragments stay in alignment  Comminuted o Bone breaks into more than two fragments.  Linear o The fracture runs parallel to the long axis of the bone.  Oblique o The fracture occurs at a slanted angle to the shaft of the bone.  Spiral o The fracture encircles the bone, and a transverse fracture occurs straight across the bone.  Pathological (insufficiency or fragility) o A fracture resulting from force that would not fracture a normal bone o Caused by weakening of the bone structure by pathological processes such as osteoporosis  Stress o Fracture due to exposure to repeated strain, often with sport activities o The forces placed on the bone are cumulative, eventually causing a fracture.  A, Oblique: Fracture at oblique angle across both cortices. o Cause: Direct or indirect energy, with angulation and some compression.  B, Occult: Fracture that is hidden or not readily discernible. o Cause: Minor force or energy.  C, Open: Skin broken over fracture; possible soft tissue trauma. o Cause: Moderate to severe energy that is continuous and exceeds tissue tolerance.  D, Pathologic: Transverse, oblique, or spiral fracture of bone weakened by tumor pressure or presence. o Cause: Minor energy or force, which may be direct or indirect.  E, Segmented: Fracture with two or more pieces or segments. o Cause: Direct or indirect moderate to severe force.  F, Spiral: Fracture that curves around cortices and may become displaced by twist. o Cause: Direct or indirect twisting energy or force with distal part held or unable to move.  G, Transverse: Horizontal break through bone. o Cause: Direct or indirect energy toward bone.  H, Greenstick: Break in only one cortex of bone. o Cause: Minor direct or indirect energy.  I, Impacted: Fracture with one end wedged into the opposite end of the inside of the fractured fragment. o Cause: Compressive axial energy or force directly to distal fragments. Fracture Healing:  When a bone is broken, the periosteum and blood vessels in the cortex, marrow, and surrounding soft tissues are disrupted. Bleeding occurs from the damaged ends of the bone and from the neighboring soft tissue.  A clot (hematoma) forms within the medullary canal, between the fractured ends of the bone, and beneath the periosteum  Bone tissue immediately adjacent to the fracture dies.  This dead tissue (and any debris in the fracture area) stimulates vasodilation, exudation of plasma and leukocytes, and infiltration by inflammatory leukocytes, growth factors, and mast cells that simultaneously decalcify the fractured bone ends.  The hematoma converts to granulation tissue (consisting of new blood vessels, fibroblasts, and osteoblasts).  Within 48 hours after injury, vascular tissue from surrounding soft tissue and the marrow cavity invades the fracture area, and blood flow to the entire bone increases.  Bone-forming cells in the periosteum, endosteum, and marrow are activated to produce subperiosteal procallus along the outer surface of the shaft and over the broken ends of the bone  Osteoblasts within the procallus synthesize collagen and matrix, which becomes mineralized to form callus.  As the repair process continues, remodeling occurs, during which unnecessary callus is resorbed and trabeculae are formed along lines of stress as the repair tissues align with the tissue cells of the host  Two methods o Direct (primary) healing (seen w/ fixation devices such as screws & pins)  Intramembranous bone formation occurs when adjacent bone cortices are in contact with one another, such as when surgical fixation devices are used.  No callus formation occurs with direct bone healing. o Indirect (secondary) healing (seen w/ cast application)  Involves bone formation, development of callus, and eventual remodeling of solid bone..  Callus formation is the hallmark. o Both require integration of cells, signaling pathways, and various molecules. Factors Impairing Healing:  Displacement and site of the fracture  Blood supply  Other local tissue injury  Immobilization  Healing time for fractures increases with age.  Ossification may be slowed or even stopped by o Inadequate immobilization o Excessive movement of fracture fragments o Infection o Poor nutrition o Systemic disease (e.g., diabetes). Clinical Manifestations:  Unnatural alignment (deformity)  Swelling  Muscle spasm Pain/tenderness  Bruising  Decreased mobility  Numbness o Immediately after a bone is fractured, numbness often occurs because of trauma to the nerve(s). o The numbness may last several minutes.  Severe pain follows numbness. Causes include o Muscle spasms o Overriding of the fracture segments o Damage to adjacent soft tissues  Pathologic fractures o Angular deformity o Painless swelling o Generalized bone pain  Stress fractures o Painful because of accelerated remodeling  Initially, pain occurs during activity and is relieved by rest. o Local tenderness o Soft tissue swelling Diagnostic Procedures:  X-ray  CT scan  MRI Disease Trajectory:  The overall goals of fracture treatment are o Anatomic realignment of bone fragments through reduction o Immobilization to maintain realignment o Restoration of normal or near-normal function of the injured part  Most musculoskeletal injuries are not life threatening.  Most fractures heal without complications  Open fractures, fractures with severe blood loss, and fractures that damage vital organs (e.g., lung, heart) are medical emergencies requiring immediate attention. Fracture Complications:  Direct complications o Infection o Problems with bone union  Nonunion is failure of the bone ends to grow together.  Delayed union is union that does not occur until approximately 8 to 9 months after a fracture.  Malunion is the healing of a bone in an incorrect anatomic position. o Avascular necrosis  Death of bone tissue due to a lack of blood supply.  Indirect complicationso Compartment syndrome  Swelling causes increased pressure within a muscle compartment.  Compresses nerves and blood vessels.  Venous thromboembolism  Fat embolism syndrome (FES)  Breakdown of skeletal muscle (rhabdomyolysis)  Hypovolemic shock Treatment:  Nondisplaced fracture o Adequate immobilization with a splint or cast  Displaced fracture o Realigning the bone fragments (reduction) close to their normal or anatomic position AND o Holding the fragments in place (immobilization) so that bone union can occur Fracture Reduction:  Closed manipulation/reduction o Nonsurgical, manual realignment of bone fragments o Used when the contour of the bone is in fair anatomic alignment and can be manually placed into normal alignment, o Once reduced, alignment is maintained with immobilization.  Splints and casts are used to immobilize and hold a closed reduction in place.  Open reduction o A surgical procedure that exposes the fracture site o Fragments are then manipulated into alignment under direct visualization. o Hardware is used (e.g., screw, plate, nail, or wire) to maintain the reduction.  This is called internal fixation  External fixation o A procedure in which pins or rods are surgically placed into uninjured bone near the fracture site and then stabilized with an external frame of bars o A method used to treat fractures that would not be adequately stabilized with a cast  Traction o Used to accomplish or maintain reduction. o Uses weights to apply firm, steady traction (pull) and countertraction (in the opposite direction) to the long axis of the bone.  Traction stretches and fatigues muscles that have pulled the bone fragments out of place, more readily allowing the distal fragment to align with the proximal fragment.  Skin traction o Used when 5-10 pounds of pulling force are needed to realign the fragments or when the traction will be used only for a brief time o Helps to diminish muscle spasms  Skeletal traction o A pin or wire is drilled through the bone distal to the fracture site.o A traction bow, rope, and weights (5 to 45 pounds) are attached to the pin or wire to apply tension and to provide the pulling force required to overcome the muscle spasm and help realign the fracture fragments. Respiratory (approx. 10 questions) ARDS Acute Respiratory Distress Syndrome (ARDs):  Acute lung injury that results from inflammation  More specifically: o “the acute onset of bilateral infiltrates on chest radiograph not explained by cardiac failure or fluid overload o A low ratio of the partial pressure of arterial oxygen to the fraction of inhaled oxygen.” ARDS Pathophysiology:  Injury occurs which then initiates the release of proinflammatory cytokines  The inflammatory response increases capillary permeability  This results in fluid and inflammatory byproducts being pushed into the interstitial spaces and then the alveoli resulting in a V/Q mismatch  Platelets and complement are activated and increase the individual’s coagulability and can form microthrombi  Surfactant production is also decreased which leads to stiffer, less compliant lungs  The massive release of inflammatory mediators can also spread systemically causing SIRS (systemic inflammatory response syndrome)  Once the issue starts to resolve, remodeling and fibrosis occur  This can lead to permanent fibrosis, lack of compliance, and prolonged respiratory issues ARDS Risk Factors:  Advanced age  Genetics  Sepsis  Trauma  Multiple transfusions (TRALI)  Pneumonia  Burns  Aspiration  Pancreatitis  Inhalation injury ARDS Manifestations:  Neuro: Altered LOC, dizziness  CV: tachycardia; hypotension  Resp: tachypnea; dyspnea and hypoxemia that are not responsive to oxygen; crackles; diminished breath sounds; pink frothy sputum  GI: possible n/v  GU: possible oliguria  Integ/Musc: weakness; paresthesia; cyanosis; delayed capillary refill;ARDS Labs and Diagnostics:  Labs o ABGs  Respiratory alkalosis early  Metabolic acidosis late o CBC o Chemistry Panel o Coagulation studies o ESR, CRP o Labs associated with organ dysfunction  Diagnostics o Chest x-ray  Bilateral infiltrates ARDS Pharmacology:  Oxygen and likely mechanical ventilation  Pharmacology is focused on stab