Portal Hypertension

A presentation on the pathology and current management (with Especial emphasis on surgical management) of Portal Hypertension; a common complication of liver cirrhosis among other liver diseases. Being a copy of seminar presentation I for the HepatoPancreaticoBiliary Unit of the Division of General Surgery, Ahmadu Belllo University Teaching Hospital, Zaria.

1. PORTAL HYPERTENSION By Kabir, Abdulkareem Hepatobiliary Unit, Division of General Surgery Department of Surgery ABUTH

2. OUTLINE INTRODUCTION DEFINITION ANATOMY AND PHYSIOLOGY CLASSIFICATION ETIOLOGY PATHOPHYSIOLOGY COMPLICATIONS MANAGEMENT CONCLUSION REFERENCES

3. INTRODUCTION Portal hypertension is an important cause of morbidity and mortality It is most commonly observed in patients with liver cirrhosis Is a major driver for associated complications variceal bleeding, ascites & hepatic encephalopathy

4. DEFINITION Portal hypertension can be simply defined as the sustained elevation of portal pressure above 12mmhg

5. ANATOMY

6. The portal venous system is valveless . Tributaries of the portal vein communicate with veins draining directly into the systemic circulation. These collateral communications occur at the Gastroesophageal junction, Anal canal, Falciform ligament, Splenic venous bed and left renal vein, Retroperitoneum

7. The portal vein carries 75 % of the total hepatic blood volume, owing It however provides only 50% of the liver's oxygen needs. The remaining 50% is derived from the hepatic artery which accounts for 25 % of the total hepatic blood flow.

8. ETIOLOGY

9. Presinusoidal Extrahepatic Splenic vein thrombosis Splenomegaly Splenic arteriovenous fistula Intrahepatic Schistosomiasis Congenital hepatic fibrosis Nodular regenerative hyperplasia Idiopathic portal fibrosis Myeloproliferative disorder Sarcoid Graft-versus-host disease

10. Sinusoidal Cirrhosis Viral infection Alcohol abuse Primary biliary cirrhosis Autoimmune hepatitis Primary sclerosing cholangitis Metabolic abnormality

11. Postsinusoidal Intrahepatic Vascular occlusive disease Post-hepatic Budd-Chiari syndrome Congestive heart failure Inferior vena caval web Constrictive pericarditis

12. PATHOPHYSIOLOGY

13. INCREASED VASCULAR RESISTANCE The initial factor in the etiology of portal hypertension is an increase in the vascular resistance to the portal blood flow Which is primarily determined primarily by blood vessel radius Liver disease that decreases the portal vascular radius produces a dramatic increase in the portal vascular resistance In cirrhosis, the increase occurs at the hepatic microcirculation (sinusoidal portal hypertension)

14. Obstruction and increased resistance can occur at 3 levels in relation to the hepatic sinusoids Presinusoidal venous block ( eg , portal vein thrombosis, schistosomiasis, primary biliary cirrhosis) Postsinusoidal obstruction ( eg , right sided heart failure, inferior vena caval obstruction Sinusoidal obstruction ( eg , cirrhosis)

15. INCREASED PORTAL VENOUS FLOW This is established through splanchnic arteriolar vasodilatation caused by an excessive release of endogenous vasodilators ( eg , endothelial, neural, humoral). The increase in portal blood flow aggravates the increase in portal pressure; Manifestations of splanchnic vasodilatation include increased cardiac output, arterial hypotension, and hypervolemia. Explains the rationale for treating portal hypertension with a low-sodium diet and diuretics to attenuate the hyperkinetic state.

16. Obstruction of portal venous flow results in a rise in portal venous pressure Leading to development of collateral circulation that diverts the obstructed blood flow to the systemic veins Opening and dilatation of preexisting vascular channels connecting the portal venous system and the superior and inferior vena cava

17. Formation of varices Further increase in Pressure  to the development of varices. Varices form when the HVPG exceeds 10 mm Hg; they usually do not bleed unless the HVPG exceeds 12 mm Hg (normal HVPG: 1-5 mm Hg) The gastroesophageal varices are important because of their propensity to bleed

18. Mechanisms of variceal hemorrhage Increased portal pressure contributes to increased varix size and decreased varix wall thickness  increased variceal wall tension. Rupture occurs when the wall tension exceeds the elastic limits of the variceal wall.

19. COMPLICATIONS Variceal bleeding Hepatic encephalopathy Ascites Spontaneous bacterial peritonitis Hepatorenal syndrome Bacteremia and/or endotoxemia Vascular collapse Cardiomyopathy Portal hypertensive gastropathy -

20. MANAGEMENT HISTORY Determining the cause of portal hypertension involves obtaining information on the following: History of jaundice - Previous jaundice suggests the possibility of a previous acute hepatitis, hepatobiliary disorder Recurrence of jaundice suggests the possibility of reactivation, infection with another virus, or the onset of hepatic decompensation History of blood transfusions , administration of various blood products, or intravenous drug use - These raise the possibility of infection with hepatitis B and C viruses Pruritus Family history of hereditary liver disease ( eg , hemochromatosis, Wilson disease)

21. Symptoms of liver disease include the following: Weakness, tiredness, and malaise Anorexia Sudden and massive bleeding, with or without shock on presentation Nausea and vomiting Weight loss Abdominal discomfort and pain

22. Jaundice or dark urine Edema and abdominal swelling Pruritus Spontaneous bleeding and easy bruising

23. The presence of complications of portal hypertension can be ascertained by the presence of: Hematemesis or melena -  gastroesophageal variceal bleeding or bleeding from portal gastropathy Mental status changes - Such as lethargy, increased irritability, and altered sleep patterns;  portosystemic encephalopathy Increasing abdominal girth -  ascites formation Abdominal pain and fever  spontaneous bacterial peritonitis, Hematochezia  bleeding from portal colopathy

24. Physical Examination Signs of portosystemic collateral formation include the following: Dilated veins in the anterior abdominal wall  umbilical epigastric vein shunts Venous pattern on the flanks  portal-parietal peritoneal shunting Caput medusae (tortuous paraumbilical collateral veins) Rectal hemorrhoids Ascites Paraumbilical hernia

25. Peripheral Stigmata of chronic liver disease include the following: Spider angiomas Gynecomastia in males loss of pubic hair and axillary hair Dupuytren contracture Muscle wasting Palmar erythema and leukonychia Asterixis ("flapping tremor," "liver flap") Testicular atrophy Splenomegaly

26. INVESTIGATIONS The key objectives in the assessment of an individual with suspected complication of portal hypertension are: Diagnosis of the underlying liver disease. Estimation of the functional hepatic reserve. Definition of changes in the portal venous anatomy and hepatic haemodynamic system Identification of the site of any gastrointestinal haemorrhage presenting.

27. INVESTIGATIONS FOR DIAGNOSIS OF THE UNDERLYING LIVER DISEASE. Laboratory Investigations FBC  The presence of anemia, leukopenia, and thrombocytopenia may be present in patients with cirrhosis Pancytopenia can result from hypersplenism, a common complication in patients with portal hypertension PT, INR CHEMISTRY HYPOALBUMINAEMIA AST/ALT > X3 of normal ALT/AST RATIO >2 ALCHOLIC CIRRHOSIS GGT,ALP ELEVATED IN CHOLESTASIS SERUM BILIRUBIN >3mg/dl

28. SEROLOGY HBV/HCV ALPHA FETO PROTEIN ELECTROLYTES HYPONATRIAEMIA, HYPOKALAEMIA METABOLIC ALKALOSIS STOOL MICROSCOPY RECTAL SNIP BIOPSY  Schistosomiasis

29. IMAGING Barium Swallow: It shows varices as rounded filling defects projecting from the wall of the lower oesophagus in about 90% of patients. Duplex doppler ultrasonography It enables both the liver architecture and the portal circulation to be assessed

30. CT Scanning Computed tomography (CT) scanning is a useful qualitative study when ultrasonographic evaluations are inconclusive

31. ESTIMATION OF THE FUNCTIONAL HEPATIC RESERVE. CHILD-PUGH’s Clinicolaboratory scoring system 2 clinical, 3 laboratory Predicts hepatic functional reserve with respect to Predicting operative outcome Assessing long term prognosis

32. MODEL FOR END STAGE LIVER DISEASE Bilirubin And Creatinine INR Aetiology MELD Score = 9.57 Ln( SCr ) + 3.78 Ln( Tbil ) + 11.2 Ln(INR) + 6.43 QUANTITATIVE MEASURES Galactose Elimination Aminopyrine Breath Test Indocyanine Green Clearance Hepatic Amino Acid Clearance

33. Hemodynamic Measurement of Portal Pressure Hepatic Venous Pressure Gradient (HVPG) An indirect measurement that closely approximates portal venous pressure A fluid-filled balloon catheter is introduced into the femoral or internal jugular vein and advanced under fluoroscopy into a branch of the hepatic vein Free hepatic venous pressure (FHVP) is then measured. The balloon is inflated until it is wedged inside the hepatic vein to measure the wedged hepatic venous pressure (WHVP) HVPG= WHVP-FHVP

34. VENOUS ANATOMY Selective Visceral Angiography Doppler Uss CT Angiograpy MR Angiography

35. IDENTIFICATION OF THE SITE OF GASTROINTESTINAL HAEMORRHAGE Upper Gastrointestinal Endoscopy Endoscopy (esophagogastroduodenoscopy [EGD]) is an essential diagnostic and therapeutic tool. If active variceal bleeding or an adherent clot is observed, variceal hemorrhage can be diagnosed confidently.

36. The presence of any of the following risk factors warrants a screening endoscopy to search for varices: International normalized ratio (INR) level of 1.5 or greater Hepatic venous pressure gradient (HVPG) measurement of 10 mm Hg or greater Portal vein diameter of more than 13 mm Presence of thrombocytopenia

37. TREATMENT Treatment is directed at the cause of portal hypertension Gastroesophageal variceal hemorrhage is the single most lethal complication of portal hypertension; As such, most of the following discussion focuses on the treatment of variceal hemorrhage

38. MANAGEMENT OF VARICEAL BLEEDING The management includes: Emergent Treatment, Primary And Secondary Prophylaxis Surgical Intervention

39. EMERGENT MANAGEMENT OF VARICEAL BLEEDING Establish airway protection in patients with massive upper gastrointestinal (GI) tract bleeding, especially if the patient is not fully conscious Establish 2 large-bore venous accesses for blood transfusion, NGT, Urethral catheter Start rapid infusion of crystalloids and/or colloid solution until the blood pressure is restored and the urine output is adequate while results are pending for GXM, FBC, Blood should be replaced as soon as available to achieve modest target of the hematocrit of 25-30% Once patient is haemodynamically stable, attempts should be made to stop the bleeding using the following options

40. METHODS OF STOPPING BLEEDING Use of vasoactive drugs; Vasopressin ( Terlipressin , Glypressin ) it reduces blood flow to all splanchnic organs, Use of vasopressin is also limited by adverse effects related to splanchnic vasoconstriction ( eg , bowel ischemia) and systemic vasoconstriction ( eg , hypertension, myocardial ischemia) Administered as a Continuous infusion of 0.2-0.4 IU/min Vasopressin always should be accompanied by intravenous nitroglycerin at a dose of 40 mcg/min

41. Somatostatin/Octreotide Decreases portal blood flow by splanchnic vasoconstriction, without significant systemic adverse effects Used in conjunction with endoscopic therapy Octreotide is administered at a constant infusion of 50 mcg/h

42. METHODS OF STOPPING BLEEDING cont. Endoscopic therapy Perform endoscopy as soon as possible after the patient has been resuscitated. The aim is to establish the cause of and to control the bleeding It also allows specific treatment to be provided at the time of diagnosis. Failures in endoscopic treatment may be managed with a second session of such therapy It includes Endoscopic Variceal Band Ligation and Endoscopic injection sclerotherapy

43. ENDOSCOPIC VARICEAL LIGATION EVL is the preferred endoscopic therapy in acute esophageal variceal bleeding EVL is performed using a banding device attached to the tip of the endoscope The varix is aspirated into the banding chamber, rubber band is used to ligate the entrapped varix. One to 3 bands are applied to each varix, This results in thrombosis; Ultimately, strangulation, sloughing, and fibrosis obliterate the varices

44. Endoscopic Injection Sclerotherapy This procedure is an alternative procedure when EVL is not technically feasible Treatment involves injecting a sclerosant solution into the bleeding varix, obliterating the lumen by thrombosis, Several different sclerosants are available, including; 5%sodium morrhuate , 1-3% sodium tetradecyl sulfate, and 5% ethanolamine oleate

45. Balloon-tube tamponade Used for patients with esophageal variceal hemorrhage that cannot be controlled by endoscopic and/or pharmacologic treatment Eg include; Minnesota tube, Sengstaken -Blakemore [S-B] tube, Linton- Nachlas tube) It should be employed only in patients with massive bleeding Should serve only as a temporizing measure until definitive treatment can be instituted.

46. Transjugular Intrahepatic Portosystemic Shunt (TIPSS) TIPS is a useful procedure for patients in whom bleeding has continued despite medical and endoscopic treatment, for patients with Child class C disease, and for selected patients with Child class B disease. The hepatic vein is cannulated and a tract is created through the liver parenchyma, from the hepatic to the portal vein, with a needle.

47. This is performed under ultrasonographic and fluoroscopic guidance. The tract is dilated, and an expandable metal stent is introduced, connecting the hepatic and portal systems. Blood from the hypertensive portal vein and sinusoidal bed is shunted to the hepatic vein Indications include; Active variceal bleeding despite emergency endoscopic and/or pharmacologic treatment and Recurrent variceal bleeding despite adequate endoscopic treatment.

48. Primary Prophylaxis Preventive strategies in patients who have never had previous variceal bleeding Involves use of non-selective beta blockers in cirrhotics with small varices <5mm And use of EVL in those with large varices >5mm with features high risk for bleeding

49. Secondary Prophylaxis Entails strategies employed to prevent rebleeding. Involves use of Nonselective beta-blockers Propranolol and nadolol. Endoscopic sclerotherapy Endoscopic sclerotherapy is usually performed at weekly intervals. Approximately 4-5 sessions are required for the eradication of varices. Endoscopic variceal ligation Endoscopic variceal ligation (EVL) is considered the endoscopic treatment of choice in the prevention of rebleeding. Sessions are repeated at 7- to 14-day intervals until variceal obliteration (which usually requires 2-4 sessions

50. SURGICAL INTERVENTION surgery is considered for the prevention of rebleeding when pharmacologic and/or endoscopic therapy have failed OPTIONS INCLUDE; Portosystemic shunts eg Distal Spleno -Renal Shunt Devascularization procedures eg splenectomy, gastroesophageal devascularization, and esophageal transection Orthotopic liver transplantation (OLT) - Treatment of choice in patients with advanced liver disease

51. TREATMENT OF ASCITES SALT RESTRICTION (2g/Day) Spironolactone+/- Furosemide Watch Renal Function Refractory Ascites 5-10% Options Large Vol Paracentesis + Albumin TIPS PERITONEOVENOUS SHUNT (Le Veen)

52. PREVENTION OF ENCEPHALOPATHY A sedative is administered intravenously. Neomycin lg tds by mouth should be given to reduce the intestinal flora. Lactulose 30ml tds decreases ammonia absorption from the bowel.

53. CONCLUSION Portal hypertension is a major complication of cirrhosis, and its consequences, including ascites, esophageal varices, hepatic encephalopathy, and hepatorenal syndrome, lead to substantial morbidity and mortality Early recognition and institution of preventive measures is therefore paramount especially in resource-limited settings such as ours

54. REFERENCES Archampong EQ. Spleen and Portal Hypertension. BAJA’s Principles and Practice of Surgery in the Tropics. 2015 David AG et al. Liver. Schwartz’s Principles of Surgery; 11 th Edition 2019. McGrawHill . Jesus C. Portal Hypertension; Medscape Article. Updated Nov 2017 Samonakis  DN,  Triantos  CK,  Thalheimer  U , et al. Management of portal hypertension. Postgraduate Medical Journal  2004; 80: 634-641. Illustrations courtesy of: https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/liver/portal_hypertension.pdf