Gastrointestinal System 2 PDF

GASTROINTESTINAL SYSTEM 2 MODULE NO. 12 Medicine 2| 2nd Bimonthly | S.Y. 2024 – 2025 PHYSICAL DIAGNOSIS AND HISTORY TAKING BATE’S PHYSICAL DIAGNOSIS AND HISTORY TAKING 13TH ED JAUNDICE Jaundice (or icterus) is a ye...

GASTROINTESTINAL SYSTEM 2 MODULE NO. 12 Medicine 2| 2nd Bimonthly | S.Y. 2024 – 2025 PHYSICAL DIAGNOSIS AND HISTORY TAKING BATE’S PHYSICAL DIAGNOSIS AND HISTORY TAKING 13TH ED JAUNDICE Jaundice (or icterus) is a yellowish discoloration of the skin and sclerae from increased levels of bilirubin o a bile pigment derived chiefly from the breakdown of hemoglobin Usually apparent when plasma bilirubin is >3 mg/dL The yellow color may have a greenish tinge in patients with longstanding jaundice o due to oxidation of bilirubin to biliverdin PHYSICAL EXAMINATION: GENERAL APPROACH Predominantly unconjugated bilirubin occurs from the first three mechanisms, as in hemolytic anemia (increased production) and Gilbert syndrome. Impaired excretion of conjugated bilirubin is seen in: o viral hepatitis o cirrhosis o primary biliary cirrhosis o drug-induced cholestasis ▪ from drugs such as: oral contraceptives, methyl testosterone, and chlorpromazine. Intrahepatic jaundice Atypical presentations of abdominal pain can be seen in o can be hepatocellular from damage to the elderly patients who might not mount an adequate hepatocytes, or response. o cholestatic from impaired excretion as a result of damaged hepatocytes or intrahepatic bile ducts Extrahepatic jaundice TECHNIQUES OF EXAMINATION o arises from obstruction of the extrahepatic bile ducts o most commonly the common bile ducts Gallstones or pancreatic, cholangio-, or duodenal carcinoma may obstruct the common bile duct. When the level of conjugated bilirubin increases in the blood: o it may be excreted into the urine ▪ turning the urine a dark yellowish brown or tea color Unconjugated bilirubin is not water soluble o not excreted into urine Dark urine indicates impaired excretion of bilirubin into the GI tract. Painless jaundice points to malignant obstruction of the bile ducts o seen in duodenal or pancreatic carcinoma Painful jaundice is commonly infectious in origin o as in hepatitis A and cholangitis Itching or pruritus occurs in cholestatic or obstructive jaundice when bilirubin levels are markedly elevated. CAROTENEMIA Carotenemia, the presence of the orange pigment carotene in the blood due to ingestion of carrots Presents as a yellow discoloration of the skin o especially palms and soles o not the sclera or mucous membranes ACHOLIC STOOLS When excretion of bile into the intestine is completely obstructed, the stools become gray or light colored, or acholic without bile Acholic stools may occur briefly in viral hepatitis They are common in obstructive jaundice TRANSCRIBED BY GROUP D & E 1 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Bulges Do the flanks bulge, or are there any local bulges? ○ Survey the inguinal and femoral areas. Observe for: The bulging flanks of ascites, The suprapubic bulge of a distended bladder or pregnant uterus, and Ventral, femoral, or inguinal hernias. INSPECTION First observe the general appearance of the patient ○ A patient who is pale or confused or writhing Fat with discomfort may pinpoint to an illness of Fat is the most common cause of a higher acuity compared to someone who is lying protuberant abdomen. Fat thickens the quietly. abdominal wall, the mesentery, and omentum. The umbilicus may appear sunken. A pannus, From the right side of the bed, inspect the surface or apron of fatty tissue, may extend below the contours and movements of the abdomen. inguinal ligaments. Lift it to look for SKIN inflammation in the skin folds or even for a Temperature: hidden hernia. ○ Check if the skin is warm or cool and clammy. Color: Gas ○ Note any bruises, erythema, or jaundice. Gaseous distention may be localized or Scars: generalized. It causes a tympanitic percussion ○ Describe or diagram their location. note. Selected foods may cause mild distention from increased intestinal gas Striae: production. More serious causes are intestinal ○ Old silver striae or stretch marks are normal. obstruction and adynamic (paralytic) ileus. ○ Pink–purple striae Note the location of the distention. Distention hallmark of Cushing syndrome. is more marked in obstruction in the colon Dilated veins: than in the small bowel. ○ A few small veins may be visible normally. ○ Suggest portal hypertension from cirrhosis Tumor (caput medusae) or inferior vena cava A large solid tumor, usually rising out of the obstruction. pelvis, is dull to percussion. Air-filled bowel is Rashes or ecchymoses: displaced to the periphery. Causes include ○ Ecchymosis of the abdominal wall is seen in ovarian tumors and uterine fibroids. intraperitoneal or retroperitoneal hemorrhage. Occasionally, a markedly distended bladder is Umbilicus: mistaken for such a tumor. ○ Observe its contour and location and any inflammation or bulges suggesting a hernia. Pregnancy Pregnancy is a common pelvic “mass.” Ascitic Fluid Ascitic fluid seeks the lowest point in the abdomen, producing bulging flanks that are dull to percussion. The umbilicus may protrude. Turn the patient onto one side to detect the shift in position of the fluid level (shifting dullness). Symmetry Is the abdomen symmetric? ○ Asymmetry may suggest: A hernia, An enlarged organ, or A mass. Visible organs or masses: ○ An enlarged liver or spleen may descend below the rib cage. ○ Inspect for lower abdominal masses or hernias. PULSATIONS Normal Aortic Pulsation: Frequently visible in the epigastrium in thin patients. Increased Pulsations: Inspect for signs of: ○ An abdominal aortic aneurysm (AAA), or CONTOUR OF THE ABDOMEN ○ Increased pulse pressure. Is it flat, rounded, protuberant, or scaphoid (markedly AUSCULTATION concave or hollowed)? TRANSCRIBED BY GROUP D & E 2 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Auscultate the abdomen before performing percussion or Friction Rubs Friction rubs are grating sounds with palpation, as these maneuvers may alter bowel sounds. respiratory variation. They indicate Technique: inflammation of the peritoneal surface of an ○ Place the diaphragm of the stethoscope gently on the organ, as in liver cancer, chlamydial or abdomen for up to 5 minutes. gonococcal perihepatitis, recent liver biopsy, ○ Listen for bowel sounds, which may include clicks and or splenic infarct. When a systolic bruit gurgles at a rate of 5 to 34 per minute (normoactive accompanies a hepatic friction rub, suspect sounds). carcinoma of the liver. Bowel Sounds Normal Bowel Sounds: Clicks and gurgles occurring at PERCUSSION 5–34 per minute. Purpose Hypoactive Bowel Sounds: Frequency 34 per minute. abdomen, solid or fluid-filled masses, and the size of Listening Location: Sounds are widely transmitted; the liver and spleen. listening in the RLQ is usually sufficient. Technique Percuss lightly in all four quadrants: Borborygmi ○ Tympany generally predominates due to gas in the Description: Prolonged gurgles or rumbling associated GI tract. with hyperperistalsis (“stomach growling”). ○ Scattered areas of dullness from fluid and feces are Bruits also common. Detection: Finding: ○ If a pulsatile mass (suggestive of AAA) is Protuberant abdomen with tympany throughout: detected, listen for turbulent flow (bruits) over ○ Suggests intestinal obstruction or paralytic ileus. the aorta. ○ Prevalence: 4–20% of healthy individuals may Dull areas suggest: have abdominal bruits. ○ Underlying mass or enlarged organ (guides further Friction Rubs palpation). Detection: ○ Possible causes: ○ Occur infrequently but may be heard over the Intrauterine pregnancy liver, spleen, or an abdominal mass. Ovarian tumor Associated Conditions: Distended bladder ○ Hepatoma, Large volume ascites ○ Gonococcal infection around the liver, Enlarged liver or spleen ○ Splenic infarction, Assess for ascites: ○ Pancreatic carcinoma. Note where abdominal tympany changes to dullness over solid posterior structures. Dullness in both flanks may indicate ascites Percuss the lower anterior chest above costal margins: On the right side: Dullness of the liver. On the left side: Tympany over the gastric air bubble and splenic flexure of the colon. Situs inversus (rare): Organ reversal, with air bubble on the right and liver dullness on the left. Bowel Sounds may be: Increased, as in diarrhea or early intestinal obstruction Decreased, then absent, as in adynamic ileus and peritonitis. Before deciding that bowel sounds are absent, sit down and listen where shown for 2 min or longer Venous Hum A venous hum is a rare soft humming noise with both systolic and diastolic components. It points to increased collateral circulation between portal and systemic venous systems, as in hepatic cirrhosis. Bruits A hepatic bruit suggests carcinoma of the liver or cirrhosis. Arterial bruits with both systolic and diastolic components suggest partial occlusion of the aorta or large arteries. Such bruits in the epigastrium are suspicious for renal artery stenosis or renovascular hypertension. TRANSCRIBED BY GROUP D & E 3 MODULE 12 | GASTROINTESTINAL SYSTEM 2 PALPATION Light Palpation Purpose Detects abdominal tenderness, muscular resistance, and some superficial organs and masses. Technique ○ Keep your hand and forearm on a horizontal plane, fingers together and flat on the abdominal wall. ○ Palpate with a light, gentle dipping motion in all four quadrants. Findings: ○ Identify any superficial organs, masses, hernias, and areas of tenderness or increased resistance. PERITONITIS ○ Resistance: Peritonitis Inflammation of the parietal peritoneum, signaling an acute Voluntary guarding often decreases with relaxation Definition intra-abdominal inflammatory process requiring urgent techniques. evaluation. Involuntary guarding (rigidity) persists and may suggest peritonitis. Signs of Positive Cough Test: Pain with coughing. ○ Relaxation techniques: Peritonitis Involuntary Guarding: Uncontrolled muscle contraction due Bend the lower extremities at the hip. to peritoneal irritation. Mouth-breathe with jaws open. Palpate after the patient exhales to relax abdominal Rigidity: Persistent abdominal stiffness, significantly indicative muscles. of peritonitis. Rebound Tenderness: Pain when palpation pressure is quickly released. Percussion Tenderness: Pain upon abdominal tapping Clinical Positive Signs: Double the likelihood of peritonitis. Implications Rigidity: Makes peritonitis almost four times more likely. Common Inflammatory, infectious, or ischemic processes such as: Causes - Appendicitis - Diverticulitis - Cholecystitis Deep Palpation - Bowel ischemia or perforation Purpose Used to delineate the liver edge, kidneys, and abdominal Examination Pre-Palpation: Ask patient to cough and locate pain areas. masses. Technique Palpation: Start with one finger, then use the full hand to Technique: locate pain. Place one hand over the other for deeper pressure. Using the palmar surfaces of fingers, press down in all Peritoneal Signs: Check for guarding, rigidity, and rebound tenderness. four quadrants. Findings: Identify any masses; note: Location, size, shape, consistency, tenderness, pulsations, and mobility with respiration or pressure. Correlate with percussion notes to enhance findings. Some Categories of Abdominal Masses: Physiologic: Pregnant uterus Inflammatory: Diverticulitis Vascular: Abdominal aortic aneurysm (AAA) Neoplastic: Colon cancer Obstructive: Distended bladder or dilated loop of bowel TENDER ABDOMENS Abdominal Wall Tenderness Abdominal Wall Tenderness Tenderness may originate in the abdominal wall. When the patient raises the head and shoulders, this tenderness persists, whereas tenderness from a deeper lesion (protected by the tightened muscles) decreases. Tenderness from Disease in the Chest and Pelvis SURGICAL ABDOMEN TRANSCRIBED BY GROUP D & E 4 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Acute Pleurisy Acute Diverticulitis Abdominal pain and tenderness may Acute diverticulitis is a confined result from acute pleural inflammation. inflammatory process, usually in the When unilateral, it can mimic acute left lower quadrant, that involves the cholecystitis or appendicitis. Rebound sigmoid colon. If the sigmoid colon is tenderness and rigidity are less redundant there may be suprapubic or common; chest signs are usually right-sided pain. Look for localized present. peritoneal signs and a tender underlying mass. Microperforation, abscess, and obstruction may ensue. Visceral Tenderness The structures shown may be tender to deep palpation. Usually the discomfort is dull with no muscular rigidity or PHYSICAL EXAMINATION OF THE LIVER rebound tenderness. A reassuring PERCUSSION explanation to the patient may Estimate the size of the liver by percussion. Measure the vertical prove helpful. span of liver dullness in the right midclavicular line after carefully locating the midclavicular line to improve accurate measurement. Acute Salpingitis Frequently bilateral, the tenderness of acute salpingitis (inflammation of the fallopian tubes) is usually maximal just above the inguinal ligaments. Rebound tenderness and rigidity may be present. On pelvic examination, motion of the cervix and uterus causes pain. Starting at a level well below the umbilicus in the RLQ (in an area of tympany, not dullness), percuss upward toward the liver. Identify the lower border of dullness in the midclavicular line. Tenderness of Peritoneal Inflammation Tenderness associated with peritoneal inflammation is more severe than visceral tenderness. Muscular rigidity and rebound tenderness are frequently but not necessarily present. Generalized peritonitis causes exquisite tenderness throughout the abdomen, together with board-like muscular rigidity. These signs on palpation, especially abdominal rigidity, double the likelihood of peritonitis. Local causes of peritoneal inflammation include: Acute Cholecystitis Signs are maximal in the right upper Estimates of liver span by percussion have a 60% to 70% quadrant. Check for Murphy sign correlation with actual span. The span of liver dullness is increased when the liver is enlarged. The span of liver dullness is decreased when the liver is small or when there is free air below the diaphragm, as from a perforated bowel or hollow viscus. Liver dullness may be displaced downward by the low diaphragm of chronic obstructive pulmonary disease. Span, however, remains normal. PALPATION Acute Appendicitis Palpate for the liver edge below the right costal margin. Place your Right lower quadrant signs are typical right hand on the patient’s right abdomen lateral to the rectus of acute appendicitis but may be muscle, with your fingertips. absent early in the course. The typical area of tenderness, McBurney point, is illustrated. Examine other areas of the right lower quadrant as well as the right flank. Acute Pancreatitis In acute pancreatitis, epigastric tenderness and rebound tenderness and localized guarding are usually present, but the abdominal wall may be soft. Firmness or hardness of the liver, bluntness or rounding of its edge, and surface irregularity are suspicious for liver disease. An obstructed distended gallbladder may merge with the liver, forming a firm oval mass below the liver edge and an area that is dull to percussion. HOOKING TECHNIQUE May be helpful, especially when the patient is obese. Stand to the right of the patient’s chest. Place both hands, side by side, on the right abdomen below the border of TRANSCRIBED BY GROUP D & E 5 MODULE 12 | GASTROINTESTINAL SYSTEM 2 liver dullness. Press in with your fingers and up toward the costal margin. Ask the patient to take a deep breath. The liver edge If percussion dullness is present, palpation correctly shown in Figure 19-18 is palpable with the fingerpads of detects splenomegaly more than 80% of the time. both hands. Fluids or solids in the stomach or colon may also cause dullness in Traube space. Downward Displacement of the Liver by a Low Diaphragm This finding is common when the diaphragm is flattened and low, as in COPD. The liver edge may be palpable well below the costal margin. Percussion, however, reveals a low upper edge, and the vertical span of the liver is normal. Smooth Large Liver Cirrhosis may produce an enlarged liver with a firm, nontender edge. The cirrhotic liver may also be scarred and contracted. Many other diseases may produce similar findings such as hemochromatosis, amyloidosis, and lymphoma. An enlarged liver with a smooth, tender edge suggests inflammation, as in hepatitis, or venous congestion, seen in right-sided heart failure. Normal Variations in Liver Shape In some individuals the right lobe of the liver may be elongated and easily palpable as it projects Check for a splenic percussion sign (Castell sign). downward toward the iliac crest. Such an elongation, A change in percussion note from tympany to dullness on sometimes called Riedel lobe, represents a variation inspiration is a positive splenic percussion sign, but this in shape, not an increase in liver volume or size. sign is only moderately useful for detecting splenomegaly. PALPATION Irregular Large Liver Palpate for the splenic edge. An enlarged liver that is firm or hard with an irregular edge or surface suggests hepatocellular carcinoma. There may be one or more nodules. The liver may or may not be tender. PHYSICAL EXAMINATION OF THE SPLEEN PERCUSSION Two techniques may help you to detect splenomegaly, an enlarged spleen: TRANSCRIBED BY GROUP D & E 6 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Causes of bladder distention: outlet obstruction from a urethral stricture or prostatic hyperplasia; medication side effects; and neurologic disorders, such as stroke and multiple sclerosis. Suprapubic tenderness is common in bladder infection. PHYSICAL EXAMINATION OF THE AORTA PALPATION Identify aortic pulsations. In adults over age 50 years, assess the width of the aorta by pressing deeply in the upper abdomen with one hand on each side of the aorta. In this age group, a normal aorta is not more than 3 cm wide. Detection of pulsations is affected by abdominal girth and the diameter of the aorta. PHYSICAL EXAMINATION OF THE KIDNEYS PERCUSSION The kidneys are retroperitoneal and usually not palpable unless markedly enlarged. Assess percussion tenderness over the CVA Start by explaining the maneuver to the patient. In patients suspected to have renal colic or pyelonephritis, CVA tenderness can be elicited due to inflammation of the renal capsule. Pain with pressure or fist percussion supports pyelonephritis if associated with fever and dysuria but may also be musculoskeletal. Abdominal Aortic Aneurysm > A periumbilical or upper abdominal mass with expansile pulsations that is ≥3 cm in diameter suggests an AAA. >Sensitivity of palpation increases as AAAs enlarge. Risk factors for AAA: age ≥65 years, history of smoking, male gender, and a first-degree relative with a history of AAA repair PHYSICAL EXAMINATION OF THE URINARY BLADDER PERCUSSION Normally, the urinary bladder is not palpable unless it is distended above the symphysis pubis. Percuss for dullness and the height of the urinary bladder above the symphysis pubis. Bladder volume must be 400 to 600 mL before dullness Screening by palpation followed by ultrasound decreases appears. mortality, especially in male smokers 65 years or older. On palpation, the dome of the distended bladder feels Pain may signal rupture. Rupture is 15 times more likely in smooth and round. AAAs >4 cm than in smaller aneurysms, and carries an Check for tenderness. 85% to 90% mortality rate. TRANSCRIBED BY GROUP D & E 7 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Note that the USPSTF recommends ultrasound screening for men over 65 years who have “ever smoked. SPECIAL TECHNIQUES: PHYSICAL EXAMINATION OF PATIENTS WITH ASCITES PHYSICAL EXAMINATION OF PATIENTS WITH ASCITES Protuberant abdomen with bulging flanks is suspicious for ascites the most common complication of cirrhosis Assessing Possible Ascites 1. Percuss from area of central tympany to area of dullness on supine patient. 2. Test for shifting dullness PHYSICAL EXAMINATION OF PATIENT WITH ACUTE CHOLECYSTITIS Murphy Sign ○ When a patient present with RUQ pain ○ performed by palpating the subcostal region during inspiration. 3. Fluid wave utilized test to detect an impulse transmitted through ascitic fluid from one flank to the opposite side 4. Ballottement Straighten the stiffer the themes of the hand together, place them on the abdominal surface, and make a briet jabbing movement directly toward the anticipated structure. PHYSICAL EXAMINATION OF PATIENT WITH VENTRAL HERNIAS Assessing Ventral Hernias ○ hernias in the abdominal wall exclusive of groin hernias ○ ask the patient to raise both legs off the table or perform a Valsalva maneuver to increase PHYSICAL EXAMINATION OF PATIENTS WITH ACUTE intraabdominal pressure APPENDICITIS Appendicitis is a common cause of acute abdominal pain Assessing Abdominal Wall Mass especially in the RLQ. ○ masses in the abdominal wall rather than inside McBurney Sign the abdominal cavity. ○ McBurney point lies 2 in from the anterior superior iliac spine on a line drawn from that process to the umbilicus. ○ Palpate the tender area for guarding, rigidity, and rebound tenderness. Rovsing Sign (indirect tenderness) Psoas Sign Obturator Sign VIRAL HEPATITIS A SALIENT FEATURES Rarely fatal Does not cause a chronic hepatitis Deaths usually occur only in those with other liver diseases TRANSMISSION TRANSCRIBED BY GROUP D & E 8 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Viral transmission is primarily person to person through the fecal-oral route and can be reduced by handwashing with soap and water after using the bathroom or changing diapers and before preparing or eating food VACCINE INDICATION All children at age 1 Persons with chronic liver disease Groups at increased risk of acquiring HAV VIRAL HEPATITIS B SALIENT FEATURES More serious health threat than HAI Fatality rate for acute infection can be up to 1.5%, and HBV infection can become chronic TRANSMISSION PATHOLOGY HBV is spread by the blood, semen, or other bodily fluids ROBBINS & COTRAN PATHOLOGIC BASIS OF DISEASE, 11TH ED of an infected person; sexual contact, injection drug use, DOC CASIO PPT: and perinatal transmission are the most common https://drive.google.com/drive/folders/1SkoCO2ZwYDlPkw5x6WigLw-AGZ3T5eTr pathways. PANCREAS PHYSIOLOGY, ANATOMY, AND HISTOLOGY OF ENDOCRINE VACCINE INDICATION AND EXOCRINE PANCREAS Beginning at birth Diseases affecting the pancreas can be the source of Previously unvaccinated children younger than 19 years. significant morbidity and mortality. For adults, vaccine recommendations target high-risk Unfortunately, despite its physiologic importance, the groups retroperitoneal location of the pancreas and the generally vague nature of signs and symptoms associated with its injury VIRAL HEPATITIS C or dysfunction allow many pancreatic diseases to progress SALIENT FEATURES undiagnosed for extended periods of time. Most prevalent chronic bloodborne pathogen Adjacent vessels and ligaments serve to demarcate the organ into a head, body, and tail. TRANSMISSION Endocrine portion: HCV is mainly transmitted by percutaneous exposures, ○ Only 1% to 2% of the pancreas particularly injection drug use, health care workers with ○ Composed of about 1 million cell clusters (The islets of needlestick injury or mucosal exposure to HCV-positive Langerhans (insulin, glucagon, and somatostatin = D blood cells) ○ We have here the alpha, beta, and delta cells VACCINE INDICATION Exocrine portion: Screening tests for HCV are very sensitive. ○ Acinar cells responsible for the synthesis of digestive Antiviral treatment regimens enzymes (mostly inactive pro-enzymes stored zymogen granules). COLORECTAL CANCER ○ Pancreatic enzymes, from the pancreatic duct of Epidemiology Wirsung & the accessory duct of Santorini, drains into Colorectal cancer is the third most frequently diagnosed and is mixed with bile (from the Common Bile Duct) in cancer among both men and women. the Ampulla of Vater (hepato-pancreatic ampulla). ○ The ampulla opens into the sphincter of Oddi (Major Prevention duodenal papilla) situated in the second part of the Decreased tobacco use; increased uptake of screening, duodenum, 7-10 cm from the pylorus, at the level of the which both prevents cancers and increases detection of second or third lumbar vertebrae. early-stage curable cancers; and improved treatments ○ The epithelial cells lining the ducts also are active participants in pancreatic secretion: The strongest risk factors for colorectal cancer are: Cuboidal cells lining the smaller ductules secrete increasing age, personal history of colorectal cancer, bicarbonate-rich fluid adenomatous polyps, or longstanding inflammatory bowel Columnar cells lining the larger ducts produce disease (IBD); and family history of colorectal neoplasia mucin, & also express the cystic fibrosis transmembrane conductance regulator (CFTR) = The most effective prevention strategy is to: affects the viscosity of the pancreatic secretions Screen for and remove precancerous adenomatous ○ Autodigestion of the pancreas (e.g., in pancreatitis) can polyps. Screening programs using fecal blood testing or be a catastrophic event. flexible sigmoidoscopy ○ “Fail-safe” Mechanisms to minimize the risk of occurrence of this phenomenon: Physical activity, aspirin, and other NSAIDs, and postmenopausal Pancreatic enzymes synthesized as inactive combined hormone replacement therapy (estrogen and progestin) proenzymes and sequestered in membrane- also protect against colorectal cancer. bound zymogen granules Activation of proenzymes requires conversion of trypsinogen to trypsin by duodenal enteropeptidase (enterokinase). Trypsin inhibitors (e.g., SPINK1, also known as pancreatic secretory trypsin inhibitor) also are secreted by acinar and ductal cells. Trypsin cleaves and inactivates itself, a negative feedback mechanism that normally p[puts a limit on local levels of activated trypsin. Acinar cells = resistant to the action of activated enzymes such as trypsin, chymotrypsin, and phospholipase A2 TRANSCRIBED BY GROUP D & E 9 MODULE 12 | GASTROINTESTINAL SYSTEM 2 ETIOLOGY, PATHOLOGY, AND SYMPTOMATOLOGY OF THE FOLLOWING PANCREATIC DISEASE CONGENITAL ANOMALIES AGENESIS Pancreas totally absent, with additional severe malformations that are incompatible with life PANCREAS DIVISUM Most common clinically significant congenital pancreatic anomaly; duct systems of fetal pancreatic primordia fail to fuse. The main pancreatic duct drains only a small portion of the head of the gland, while the bulk of the pancreas (from the dorsal pancreatic primordium) drains through the minor sphincter, which has a narrow opening. Elevated intraductal pressure throughout most of the pancreas; increased risk for chronic pancreatitis. ANNULAR PANCREAS Band-like ring of normal pancreatic ACUTE PANCREATITIS tissue that Characterized by reversible pancreatic parenchymal injury and completely encircles inflammation and has many causes, including toxic exposures the second portion of (alcohol), pancreatic duct obstruction (biliary calculi), inherited the duodenum genetic defects, vascular injury, and infections. Annular pancreas Acute pancreatitis results from inappropriate release and activation can produce of pancreatic enzymes that, in turn, destroy pancreatic tissue and duodenal obstruction elicit an acute inflammatory reaction. ECTOPIC PANCREAS Pancreatic tissue found most commonly in the stomach and the duodenum. Jejunum, Meckel diverticulum and ileum are also favored sites for pancreatic ectopia. Composed of normal-appearing pancreatic acini, glands and langerhans. Can cause pain from localized inflammation and mucosal bleeding CONGENITAL CYSTS Are typically unilocular and vary in size from microscopic to 5 cm in diameter. They are lined by cuboidal or flattened epithelium and filled with clear serous fluid, which distinguishes them from pancreatic cystic neoplasms that often contain mucin. PANCREATITIS Pancreatitis is divided into two forms: acute and chronic. Both are initiated by injuries that lead to auto-digestion of the pancreas by its own enzymes. Under normal circumstances, several factors protect the pancreas from autodigestion: Inappropriate trypsin activation within the pancreas can Most digestive enzymes are synthesized as inactive activate other proenzymes such as: prophospholipase proenzymes (zymogens) and packaged within secretory and proelastase, which degrade fat cells and damage the granules. elastic fibers of blood vessels, respectively. Proenzymes are typically activated by trypsin, which itself Once tissue damage commences, trypsin can also directly is activated by duodenal enteropeptidase (enterokinase) in or indirectly activate factors found in the blood, including the small bowel; as a result, intrapancreatic activation of components of the coagulation, complement, kallikrein, proenzymes is normally minimal. and fibrinolytic pathways. Acinar and ductal cells secrete trypsin inhibitors, including The resulting inflammation and small-vessel thrombosis serine protease inhibitor Kazal type 1 (SPINK1), which causes further damage to acinar cells, amplifying further limit intrapancreatic trypsin activity. intrapancreatic enzyme activation. Pancreatitis occurs when these protective mechanisms are disrupted or overwhelmed. CHRONIC PANCREATITIS Prolonged inflammation of the pancreas is associated with irreversible destruction of exocrine parenchyma, fibrosis, and, in the late stages, loss of endocrine parenchyma. The prevalence is between 0.04% and 5%; most affected patients are middle-aged males. The most common cause is long-term alcohol use. TRANSCRIBED BY GROUP D & E 10 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Pseudocysts typically arise following a bout of acute pancreatitis, particularly one superimposed on chronic alcoholic pancreatitis. Traumatic injury to the pancreas can also give rise to pseudocysts. Pseudocysts may be situated within the pancreas or, more commonly, in the lesser omental sac or in the retroperitoneum between the stomach and transverse colon or between the stomach and liver. They can even be subdiaphragmatic. Pseudocysts are lined by fibrous tissue and granulation tissue and range in size from 2 to 30 cm in diameter. PANCREATIC NEOPLASM Chronic pancreatitis has been associated also with the CYSTIC NEOPLASM following conditions: Cystic neoplasms are diverse tumors that range from ○ Long-standing obstruction of the pancreatic duct harmless benign cysts to lesions that are precursors to by calculi or neoplasms invasive, potentially lethal, cancers. ○ Autoimmune injury Virtually all serous cystic neoplasms are benign. ○ Hereditary factors; up to 25% of chronic Noninvasive intraductal papillary mucinous neoplasms and pancreatitis has a genetic basis. mucinous cystic neoplasms are almost always curable, but Chronic pancreatitis often follows repeated episodes of both may progress to invasive, potentially lethal acute pancreatitis. carcinomas. Acute pancreatitis initiates a sequence of perilobular Each of the major cystic neoplasms has a relatively fibrosis, duct distortion, and altered secretions that, as a specific mutational profile. result of recurrent injury, leads to loss of exocrine parenchyma and fibrosis. Serous cystic neoplasms usually occur in the tail of the Chronic pancreatic injury of any cause leads to local pancreas. The cysts are small (1 to 3 mm) and can be solitary, production of inflammatory mediators that promote multiple, or present as a honeycomb of microcystic lesions. Serous fibrosis and acinar cell loss. cysts are lined by glycogen-rich cuboidal cells, and contain clear, Fibrogenic factors tend to predominate in chronic thin, straw-colored fluid (Fig. 19.8). They account for 15% to 25% of pancreatitis. These fibrogenic cytokines, including all cystic neoplasms of the pancreas and are twice as common in transforming growth factor B (TGFß) and women. Serous cystic neoplasms typically present in the sixth to platelet-derived growth factor (PDGF), induce activation seventh decade of life with nonspecific symptoms such as and proliferation of pancreatic stellate cells (periacinar abdominal pain, but many are detected incidentally during imaging myofibroblasts), collagen deposition, and fibrosis. for another indication. Surgical resection is curative in the vast Chronic pancreatitis is characterized by parenchymal majority of patients. Inactivation of the VHL tumor suppressor gene fibrosis, acinar atrophy and dropout, and variable ductal on chromosome 3p is the most common genetic abnormality in dilation. serous cystic neoplasms. Acinar loss is a constant feature, but there is usually relative sparing of the islets of Langerhans, which become embedded in the sclerotic tissue and may fuse and appear enlarged. Ductal epithelium may be atrophic, hyperplastic, or metaplastic (squamous). Chronic pancreatitis caused by alcohol abuse is characterized by ductal dilation and intraluminal protein plugs and calcifications. AUTOIMMUNE PANCREATITIS Autoimmune pancreatitis is a pathogenically distinct form of chronic pancreatitis that comes in two distinct forms, Close to 95% of mucinous cystic neoplasms arise in each with its own characteristic histopathology: women and, in contrast to serous cystic neoplasms, they are ○ Autoimmune pancreatitis type 1 precursors to invasive carcinomas. These neoplasms usually arise in Associated with the presence of the tail of the pancreas and present as painless, slow growing immunoglobulin G4 masses. The cystic cavities are larger than those in serous cystic (IgG4)-secreting plasma cells in the neoplasms and are filled with thick, tenacious mucin. The columnar pancreas and is one manifestation of mucin-producing epithelium that lines the cysts is associated with a a systemic IgG-related disease. dense stroma similar to ovarian stroma (Fig. 19.9). The latter ○ Autoimmune pancreatitis type 2 frequently expresses estrogen and progesterone receptors as well Restricted to the pancreas with the as other markers of the ovarian stroma, such as inhibin. Surgical exception of a subset of patients with resection is curative for noninvasive mucinous cystic neoplasms, but ulcerative colitis. up to one third harbor an invasive adenocarcinoma. Up to 50% of Both variants of autoimmune pancreatitis may mimic patients with an invasive adenocarcinoma arising in a mucinous pancreatic carcinoma, including: cystic neoplasm will succumb to their disease within 5 years; ○ presentation as a "mass lesion" in the therefore, early detection and treatment, before invasive cancer pancreatic head on imaging. develops, is critical. Mucinous cystic neoplasms harbor oncogenic Autoimmune pancreatitis, which responds to steroid KRAS mutations in approximately half of cases, while mutations of therapy, is therefore important to distinguish from TP53 and SMAD4 are typically observed in invasive neoplasms neoplasia. arising from these cysts. Recently, loss-of-function mutations of RNF43, which encodes an E3 ubiquitin ligase that normally PANCREATIC NON NEOPLASTIC CYST downregulates Wnt signaling, have been described in up to one-third of mucinous cystic neoplasms. Similar RNF43 mutations also occur PANCREATIC PSEUDOCYST in colorectal cancers. Are formed when areas of intrapancreatic or peripancreatic hemorrhagic fat necrosis are walled off by fibrosis and granulation tissue. These lesions, which account for 75% of all pancreatic cysts, are referred to as pseudocysts because they lack an epithelial lining. TRANSCRIBED BY GROUP D & E 11 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms that involve the larger ducts of the pancreas. In contrast to mucinous cystic neoplasms, IPMNs arise more frequently in men and tend to involve the head of the pancreas. Up to 20% are multifocal. Two features are useful in distinguishing IPMNs from mucinous cystic neoplasms: (1) absence of the dense “ovarian” stroma seen in mucinous cystic neoplasms and (2) involvement of a pancreatic duct (Fig. 19.10). Just as with mucinous cystic neoplasms, IPMNs can progress to an invasive cancer; early detection and treatment before progression to invasive Pathogenesis cancer is thus critical. Similar to mucinous cystic neoplasms, As with other carcinomas, pancreatic cancer is the product intraductal mucinous papillary neoplasms harbor oncogenic KRAS of complementary mutations and epigenetic alterations mutations in approximately 80% of tumors and loss of-function that alter the expression of oncogenes and tumor RNF43 mutations in up to 50%. TP53 and SMAD4 mutations suppressor genes. The most common molecular typically occur only with transition to invasive cancer. Notably, alterations in pancreatic carcinogenesis are summarized oncogenic mutations of GNAS, which encodes the alpha subunit of in Table 19.3 and include the following. the stimulatory G protein, Gsα, are present in approximately KRAS (chromosome 12p) is the most frequently two-thirds of IPMNs but are not found in other pancreatic cysts. altered oncogene in pancreatic cancer, with activating point mutations present in greater than 90% of cases. These result in constitutive activation of Ras, a small, guanosine triphosphate (GTP)–binding protein enzyme that normally participates in signaling events downstream of growth factor receptors with intrinsic tyrosine kinase activity. Ras signaling activates several downstream pathways that augment cell growth and survival, most notably the mitogen-activated protein kinase (MAPK) and PI3K/AKT pathways. CDKN2A (chromosome 9p) is inactivated in 30% of pancreatic cancers through point mutations or homozygous deletions. This complex locus encodes two tumor suppressor proteins : p16/INK4a, a cyclin PANCREATIC CARCINOMA dependent kinase inhibitor that antagonizes cell cycle Infiltrating ductal adenocarcinoma of the pancreas, progression, and ARF, a protein that augments the more commonly known as pancreatic cancer, is the third function of the p53 tumor suppressor protein. leading cause of cancer deaths in the United States, trailing SMAD4 (chromosome 18q) is inactivated in 55% of only lung and colon cancers, and has one of the highest pancreatic cancers. SMAD4 encodes a tumor suppressor mortality rates of any cancer. that plays an important role in signal transduction from the Pancreatic cancer is one of the most aggressive of the TGFβ family of cell surface receptors. SMAD4 is only solid cancers. rarely inactivated in other cancer types. Cigarette smoking is a significant cause of pancreatic TP53 (chromosome 17p) is inactivated in 70% to 75% of cancer. pancreatic cancers. This gene encodes the tumor Cancer-causing germline mutations are present in 10% of suppressor p53, a nuclear DNA-binding protein that can patients. respond to DNA damage by arresting cell growth, inducing Invasive pancreatic cancer arises from histologically cell death (apoptosis), or causing cellular senescence. well-defined precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). Ductal adenocarcinomas are highly invasive and elicit an intense desmoplastic response. The genes most frequently mutated or otherwise altered in pancreatic cancer include KRAS, p16/CDKN2A, TP53, and SMAD4; transcriptional profiles can be used to define the highly aggressive basal-like and somewhat less aggressive classical subtypes. Patients often present with abdominal pain and weight loss, sometimes accompanied by jaundice and deep vein thrombosis. New-onset diabetes is detected in up to half of cases. TRANSCRIBED BY GROUP D & E 12 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Also seen are less common mutations that affect genes involved in DNA repair or regulation of chromatin structure. DNA methylation (epigenetic) abnormalities. DNA methylation abnormalities are widespread in pancreatic cancer. For example, promoter hypermethylation causes transcriptional silencing of tumor suppressor genes including CDKN2A. Conversely, promoter hypomethylation leads to overexpression of oncogenes such as GATA6 and BRD4. CIRRHOSIS Transcriptomic profiles and pancreatic cancer subtypes. Global analyses of gene expression have identified two distinct pancreatic cancer subtypes, termed basal-like and classical. Basal-like pancreatic cancers are highly aggressive, whereas the classical subtype has a somewhat more favorable prognosis. How these subtypes respond differentially to specific therapies is an area of active investigation. Clinical Features Carcinomas of the pancreas typically remain silent until they cause obstruction or invade into adjacent structures. Pain is usually the first symptom, but by the time pain appears these cancers are usually beyond cure. Obstructive jaundice is associated with most cases involving the pancreatic head, as these tend to block the common bile duct; this is exemplified by the Courvoisier sign, a palpably enlarged, nontender gallbladder with mild painless jaundice. Weight loss, anorexia, and generalized malaise and weakness are often signs of advanced disease. Migratory thrombophlebitis, known as the Trousseau sign, occurs in about 10% of patients and is attributable to the elaboration of platelet activating factors and procoagulants from the carcinoma or its necrotic products PORTAL HYPERTENSION LIVER HEPATIC FAILURE TRANSCRIBED BY GROUP D & E 13 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Mild liver enzyme elevation (transaminitis). Cytomegalovirus (CMV): Affects immunosuppressed patients (e.g., transplant recipients). Features: hepatomegaly, mild hepatitis, and granulomas. Herpes Simplex Virus (HSV): Rare but severe in immunocompromised patients or pregnant women. Causes necrotizing hepatitis. Yellow Fever: Flavivirus transmitted by mosquitoes. Symptoms: jaundice, fever, hemorrhage ("black vomit"). Pathology: midzonal hepatocyte necrosis. DRUG - OR TOXIN-INDUCED LIVER DISEASE Common Drugs or Toxins Causing Liver Injury: 1. Acetaminophen (dose-dependent hepatotoxicity). 2. Amoxicillin-clavulanate (idiosyncratic reaction). 3. Methotrexate (chronic liver fibrosis). 4. Alcohol (fatty liver, hepatitis). 5. Statins (rare transaminitis). 6. Herbal supplements (e.g., kava, green tea extract). Alcoholic Liver Disease: 1. Stages: ○ Steatosis (fatty liver): reversible with abstinence. ○ Alcoholic hepatitis: inflammation and necrosis; presents with jaundice and fever. ○ Cirrhosis: irreversible scarring of the liver. 2. Pathogenesis: ○ Acetaldehyde toxicity and oxidative stress from alcohol metabolism. CHOLESTASIS Neonatal Cholestasis: Prolonged jaundice in infants due to impaired bile flow. Causes: biliary atresia, metabolic disorders (e.g., alpha-1 antitrypsin deficiency). Cholestasis of Sepsis: HEPATITIS Occurs in critically ill patients. ACUTE AND CHRONIC HEPATITIS Caused by inflammatory cytokines impairing bile flow. Two Forms of Hepatocyte Injury (Cell Death): Primary Biliary Cirrhosis (PBC): 1. Necrosis: Autoimmune destruction of intrahepatic bile ducts. ○ Caused by severe cell injury. Features: fatigue, pruritus, and cholestatic pattern (↑ALP, ○ Cellular swelling, rupture, and release of ↑bilirubin). contents lead to inflammation. Associated with anti-mitochondrial antibodies (AMA). ○ Common in acute hepatitis. Primary Sclerosing Cholangitis (PSC): 2. Apoptosis: Chronic inflammation and fibrosis of intra- and ○ Programmed cell death without significant extrahepatic bile ducts. inflammation. Associated with inflammatory bowel disease (IBD), ○ Leads to eosinophilic apoptotic bodies especially ulcerative colitis. ("Councilman bodies"). Risk of cholangiocarcinoma. ○ Seen in both acute and chronic hepatitis. Diagnosed with MRCP/ERCP: "beading" appearance. Stages of Chronic Hepatitis B: HEPATIC INHERITED METABOLIC DISEASES 1. Immune-Tolerant Phase: HEREDITARY HEMOCHROMATOSIS ○ High HBV DNA levels. Excessive accumulation of body iron, (due to excessive ○ Normal ALT and minimal liver inflammation. intestinal absorption.)Total iron accumulation may exceed 2. Immune-Active Phase: 50 gm; deposited in the liver (1/3 of iron), pancreas, and ○ High ALT and active inflammation. heart. ○ HBV DNA levels variable. Most common form: autosomal recessive disease of adult 3. Inactive Carrier Phase: onset (mutations in the HFE gene). ○ Low HBV DNA, normal ALT, minimal Fully developed cases show inflammation. ○ cirrhosis (seen in all patients), ○ HBsAg positive. ○ diabetes mellitus (in 75% to 80% of patients), 4. Reactivation Phase: ○ skin pigmentation (in 75% to 80%). ○ Occurs spontaneously or with immunosuppression. Acquired forms of iron accumulation (secondary iron overload) Multiple transfusions, Autoimmune Hepatitis Ineffective erythropoiesis (as in β-thalassemia and Chronic inflammation of the liver due to autoimmunity. myelodysplastic syndromes Associated with autoantibodies: ANA, SMA (smooth Increased iron intake. muscle antibody), and anti-LKM1 (liver-kidney microsomal ○ Total body iron pool (2 to 6 gm in normal adults); antibody). about 0.5 gm is stored in the liver, 98% of which Histology shows interface hepatitis and plasma cell is in hepatocytes. infiltration. Treatable with corticosteroids and azathioprine. Morphologic Changes Responses to the deposition of hemosiderin in the following organs Other Viral Infections of the Liver (in decreasing order of severity): Epstein-Barr Virus (EBV): Causes infectious mononucleosis. TRANSCRIBED BY GROUP D & E 14 MODULE 12 | GASTROINTESTINAL SYSTEM 2 Liver = golden-yellow hemosiderin granules in the of hepatic copper content in excess of 250 µg/g dry weight cytoplasm of periportal hepatocytes, bile duct epithelium is most helpful for making a diagnosis. and Kupffer cells; liver slightly larger than normal, dense, ○ In the brain, toxic injury primarily affects the and chocolate brown to black liver. basal ganglia, particularly the putamen, which ○ Hepatic iron concentrations >22,000 µg/g dry demonstrates atrophy and even cavitation. weight = development of fibrosis and cirrhosis. ○ Eye lesions ”Kayser-Fleischer rings (green to (N: