Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences GI System – Review Problems (1) and (2) – Liver and Biliary Tree Ali Jassim Alhashli, BSc www.alhashli.com

2. Anatomy of The Liver • Blood supply: • Arterial supply: • What are the branches of celiac trunk? • Left gastric artery. • Splenic artery. • Common hepatic artery, which divides to: • Hepatic artery proper → right and left hepatic arteries. Notice that these arteries supply 50% of liver oxygen while the remaining 50% is supplied by portal vein. • Gastroduodenal artery • Venous drainage: through IVC.

3. Anatomy of The Liver • What are the important ligaments of the liver? • Falciform ligament: which attaches the liver to anterior abdominal wall and contains ligamentumteres (obliterated umbilical vein). • Coronary ligament: on the superior aspect of the liver and attaching it to the diaphragm. • Triangular ligaments (right and left): they are extension of the coronary ligament. • Hepatoduodenal ligament: contains common bile duct, portal vein and hepatic artery. • What is the bare area of the liver? • A posterior part of the liver against the diaphragm with no peritoneal covering.

4. Histology of The Liver

5. Anatomy of Biliary System • Parts of the gallbladder: • Infundibulum (Hartman’s pouch): proximal end near the cystic duct. • Fundus: distal larger end. • Valves within the cystic duct are called: valves of Heister. • Function of gallbladder: storage of bile which it collects from the liver via ducts of Luschka. • Biliary tree: right and left hepatic ducts converge to form common hepatic duct → which joins the cystic duct to form common bile duct → that empties in 2nd part of the duodenum through ampulla of Vater that is surrounded by sphincter of Oddi.

6. Bile and Jaundice

7. Bile: • It is composed of: cholersterol, lecithin, bile acids, bilirubin and water. • Function: emulsification of dietary fat facilitating its absorption. • Define enterohepatic circulation. • Bile acids which are released from the liver for emulsification of fat will be reabsorbed in the terminal ileum and transported back to the liver via hepatic portal vein. • What is cholecystokinin (CCK)? • It is a GI hormone which is released by the duodenum in response to the presence of fat in the duodenum. It causes contraction of the gallbladder and relaxation of sphincter of Oddi thus facilitating the release of bile. • Jaundice: • Definition: it is the yellowish discoloration of the sclera and mucous membranes due to increased bilirubin (< 3 g/dL). • Causes are classified to: • Pre-hepatic: hemolytic anemias (examples: spherocytosis, SCD and G6PD deficiency). Indirect bilirubin is increased. • Hepatic: hepatitis, cirrhosis or deficiency of UDP-glucouronyltransferase enzyme. Both direct and indirect bilirubin increased. • Post-hepatic: gallstone or tumor. Direct bilirubin is increased. In obstructive jaundice, alkaline phosphatase is also increased. • Gilbert’s disease vsCrigler-Najjar syndrome: • Gilbert’s disease: AR; ↓ activity of the enzyme UDP glucouronyltransferase; patients are usually asymptomatic. • Crigler-najjar syndrome: absence of the enzyme UDP glucouronyltransferase. Bile and Jaundice

8. Bile and Jaundice

9. Bile and Jaundice • Jaundice (continued): • Signs and symptoms: • Yellowish discoloration of sclera, mucous membranes and skin. • Patient might have hepatomegaly or tenderness in RUQ. • Obstructive jaundice: pale stool, dark urine and pruritis. • Courvoisier’s sign: jaundice with a PAINLESS, palpable gallbladder → seen in patients with cancer in the head of the pancreas. • Diagnosis; what investigations you will request for your patient? • CBC. • LFTs: • ALT: increased in viral hepatitis. • AST: increased in alcoholic hepatitis. • GGT: increased when there is intrahepatic or extrahepatic obstruction of bile flow. • Alkaline phosphatase: increased with obstructuve jaundice. • Serum albumin, PT/PTT and ammonia. • Other investigations might include: ultrasound, CT-scan or ERCP.

10. Viral Hepatitis

11. Viral Hepatitis

12. Viral Hepatitis

13. Viral Hepatitis

14. Portal Hypertension • Definition: it is defined as portal venous pressure < 10 mmHg (measured indirectly by hepatic vein wedge pressure). • Causes: • Pre-hepatic: portal vein thrombosis. • Intra-hepatic: cirrhosis. • Post-hepatic: Budd-Chiari syndrome (thrombosis of hepatic veins). • Signs and symptoms (including both of portal hypertension and liver failure): • Portal hypertension: splenomegaly, ascites, dilated umbilical veins, hemorrhoids, esophageal varices. • Liver failure: jaundice, hepatic encephalopathy, palmarerythema, spider angiomata and flapping tremor. • What is the rule of 2/3 in portal hypertension? • 2/3 of patients with liver cirrhosis will develop portal hypertension → 2/3 of patients with portal hypertension will develop esophageal varices → 2/3 of patients with esophageal varices will bleed from them • Porto-systemic collaterals: • Left gastric vein to esophageal vein → esophageal varices. • Umbilical vein to epigastric veins → caput medusa. • Superior rectal vein to middle and inferior rectal veins → hemorrhoids.

15. Portal Hypertension • Diagnosis: • History and physical examination. • Initially by ultrasound and then confirmed with CT-scan. • Treatment: reducing portal pressure by shunts: • Splenorenal vein: connecting splenic vein to left renal vein. • Total shunt (end-to-side): connecting end of portal vein to side of IVC. • Partial shunt (side-to-side) connecting side of portal vein to side of IVC. • Portocaval H graft: synthetic graft attached from portal vein to IVC. • Mesocaval H graft: synthetic graft attached from superior mesenteric vein to IVC. Notice that a major complications of creating a shunt is increased incidence of hepatic encephalopathy. Medical treatment: β-blockers to reduce portal pressure.

16. Hepatic encephalopathy: • Definition: it is altered mental status which occurs in patients with liver failure due to increased level of ammonia in systemic circulation. • Precipitating factors: • Infections. • GI bleeding. • Opiates and sedatives. • Electrolytes depletion. • Excess intake of dietary protein • Signs and symptoms: • Altered mental status. • Flapping tremor. • Lethargy/coma. • Diagnosis: • Abnormal LFTs. • Elevated serum ammonia. • Altered mental status. • Treatment: lactulose and neomycin. • Ascites: • Definition: excess fluid in peritoneal cavity which increases the risk for spontaneous bacterial peritonitis. • Causes: • Decreased plasma oncotic pressure (deficient albumin production by the liver). • Increased hydrostatic pressure. • Signs and symptoms: distended abdomen, shifting dullness and fluid wave. • Treatment: • Decrease intake of sodium. • Potassium-sparing diuretic (e.g. spironolactone). • Abdominal paracentesis: don’t remove high volume of fluid otherwise patient will suffer from hypovolemic shock. Portal Hypertension

17. Portal Hypertension

18. Esophageal varices: • Definition: dilated esophageal veins occurring in 2/3 of patients with portal hypertension. • Signs and symptoms: • ASYMPTOMATIC UNLESS THERE IS RUPTURE AND BLEEDING. • Rupture (upper GI bleeding):hematemesis, melena and/or hemtochezia (with massive bleeding). You might also notice features of shock! • Diagnosis: • Upper GI endoscopy. • Treatment: • To decrease risk of rupture: β-blockers. • When there is rupture: • Resuscitate the patient. • Give him octreotide. • Endoscopy with: sclerotherapy, injecting vasopressin, band ligation. • If you fail to control bleeding, try balloon tamponade (with Blakemore tube). • Caput medusa: • Definition: dilated veins around the umbilicus seen in patient with portal hypertension and accompanied by bruits. Portal Hypertension

19. Hemochromatosis: • Definition: it is an inherited genetic disorder in which there is increased absorption of iron from duodenum resulting in accumulation of iron in different organs/tissues (liver, heart, pancreas, skin and testes). • Clinical manifestations: • Liver cirrhosis (most common) with 15-20% of patients developing Hepato-Cellular Carcinoma (HCC). • Restrictive cardiomyopathy (20% of patients). • Skin hyperpigmentation. • Diabetes. • Hypogonadism. • Diagnosis: • ↑serum ferritin and serum iron with ↓TIBC. • Most accurate: • Liver biopsy. • Genetic testing for abnormal C282Y gene. • Treatment: • Phlebotomy. If phelobotomy cannot be done → iron-chelating agent (deferoxamine). • Wilson disease: • Definition: it is an autosomal recessive (AR) disorder in which there is impaired ability to excrete copper from the body resulting in accumulation of copper in liver, brain and cornea. • Clinical presentation: • Liver cirrhosis. • Kayser-Fleischer rings are found on slit-lamp examination. • Patient might present with behavioral changes and abnormal movements. • Diagnosis: • Specific: ↓ceruloplasmin level. • Most specific: liver biopsy. • Treatment: • Copper-chelating agents (penicillamine). • Liver transplantation is curative. Hemochromatosis and Wilson Disease

20. Primary Biliary Cirrhosis: • Definition: it is an autoimmune disorder which is associated with other autoimmune disease (RA, Sjogren syndrome and scleroderma). • Epidemiology: middle-aged females. • Clinical manifestations: • 1/3 of patients are asymptomatic and found to have the disease by ↑Alkaline Phosphatase (ALP) with routine examinations. • Most common symptoms are: fatigue and PRURITIS. • 1/3 of patients will have osteoporosis and hypothyroidism. • Diagnosis: • ↑ALP and Gamma GlutamylTranspeptidase (GGTP). • Most specific: positive antimitochondrial antibodies • Treatment: • Symptomatic treatment for pruritis with ursodeoxycholic acid or UV-light. • With advanced disease: definitive therapy is achieved with liver transplantation. • Primary sclerosingcholangitis: • Definition: it is an idiopathic disorder associated with IBD (especially ulcerative colitis). It also has increased risk for cancer of biliary system (15%). • Clinical manifestations (similar to primary biliary cirrhosis): fatigue and pruritis. • Diagnosis: • ↑ALP and GGTP (similar to primary biliary cirrhosis). • NEGATIVE antimitochondrial antibodies. • Most accurate way of diagnosis: Endoscopic Retrograde Cholangio-Pancreaticography (ERCP). • Treatment: • Symptomatic treatment of pruritis with ursodeoxycholic acid. • Definitive treatment with liver transplantation. Primary Biliary Cirrhosis and Primary Sclerosis Cholangitis

21. Primary Biliary Cirrhosis and Primary Sclerosis Cholangitis

22. Definition: it is an autosomal recessive disorder (AR) in which the liver produces α1 antitrypsin but cannot secrete it. Therefore, the lung cannot be protected from the action of neutrophilelastase enzyme which will damage it. • Clinical manifestations: • Most common: non-smoker patient developing emphysema at a young age. • Due to accumulation of α1 antitrypsin in the liver, 15% of patients will have liver cirrhosis. • Diagnosis: blood sample to check for • α1 antitrypsin level. • α1 genotyping. • Treatment: • Liver cirrhosis cannot be reversed. • For emphysema: patients must receive replacement of the enzyme and advice them to stop smoking (if they are smokers). α1 Antitrypsin Deficiency

23. Cholelithiasis: • Definition: it is the formation of stones in the gallbladder due to imbalance between contents of bile. • Types: • Cholesterol stones: 85%. • Pigmented stones: 15%. NOTICE THAT ONLY 15% OF GALLSTONES ARE RADIOPAQUE (BECAUSE THEY DO NOT CONTAIN SUFFICIENT CALCIUM). • Risk factors: • Remember the 4 F’s: Female, Forty, Fertile and Fat. • Others: pregnancy, OCPs, IBD and hyperlipidemia. • Signs and symptoms: • MOST PATIENTS ARE ASYMPTOMATIC. • If symptomatic: colicky pain in RUQ (radiating to back or epigastric area) which is worse when eating fatty food + nausea and vomiting. • Diagnosis: ultrasound. • Treatment: • ASYMPTOMATIC PATIENT: observation unless: • There is porcelain gallbladder (it has increased risk of cancer). • Patient is of pediatric age group. • Patient is immunocompromised. • Presence of large stones < 2-3 cm. • Patient has SCD. • SYMPTOMATIC PATIENT: cholecystectomy. Cholelithiasis and Acute Cholecystitis

24. Cholelithiasis and Acute Cholecystitis

25. Acute cholecystitis: • Definition: it is acute inflammation of the gallbladder due to a stone obstructing the cystic duct. • Signs and symptoms: • Fever. • Nausea and vomiting. • RUQ pain (which gets worse with fatty food) + presence of Murphy’s sign in 1/3 of patients (pain on deep inspiration upon palpation of RUQ). • Diagnosis: • Labs: CBC (leukocytosis), LFTs and bilirubin, amylase, urea/BUN and electrolytes. • Imaging: • Ultrasound: • Gallbladder wall < 4 mm. • Presence of stone. • Presence of fluid around gallbladder. • HIDA scan (most sensitive): filling defect of the gallbladder (not taking up the contrast due to obstruction of cystic duct). • Treatment: • NPO. • IV fluids. • Analgesia. • IV broad-spectrum antibiotics. • Cholecystectomy (laparoscopically preferred) if they present within 24-48 hours from the onset of symptoms. Cholelithiasis and Acute Cholecystitis

26. Cholelithiasis and Acute Cholecystitis