1. Cirrhosis of Liver: Continuation Nursing 2015 Part two 22 to 42slides

2. Portal systemic collaterals Distorted sinusoidal architecture leads to increased resistance Distorted sinusoidal architecture leads to increased resistance Portal vein Cirrhotic Liver Splenomegaly ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE

3. CAUSES CAUSES OF PORTAL HYPERTENSION ACCORDING TO SITE OF ABNORMALITY Extrahepatic post-sinusoidal Budd-Chiari syndrome Intrahepatic post-sinusoidal Veno-occlusive disease Sinusoidal Cirrhosis Cystic liver disease Partial nodular transformation of the liver Metastatic malignant disease Intrahepatic pre-sinusoidal Schistosomiasis Sarcoidosis Congenital hepatic fibrosis Vinyl chloride Drugs Extrahepatic pre-sinusoidal Portal vein thrombosis due to sepsis* (umbilical, portal pyaemia) or procoagulopathy (thrombotic diseases, oral contraceptives, pregnancy), or secondary to cirrhosis Abdominal trauma, including surgery Malignant disease of pancreas or liver Pancreatitis Congenital

4. Clinical complications of PHT VARICES:esophageal,gastric,anorectal,retroperit oneal. -portal hypertensive gastropathy and colopathy. -caput medusae -ascites -congestive splenomegaly -hepatic encephalopathy

5. Small varices Large varices No varices 7-8%/year Varices Increase in Diameter Progressively Merli et al. J Hepatol 2003;38:266 VARICES INCREASE IN DIAMETER PROGRESSIVELY

6. Predictors of hemorrhage:  Variceal size  Red signs  Child B/C Predictors of hemorrhage:  Variceal size  Red signs  Child B/C NIEC. N Engl J Med 1988; 319:983 Variceal hemorrhage Varix with red signs PROGNOSTIC INDICATORS OF FIRST VARICEAL HEMORRHAGE

7. Treatment of portal hypertension -treatment of complications:variceal bleeding,,,ascites… -endoscopic procedures:sclerotherapy +band ligation+prophylactic propranolol

8. Treatment of Acute Variceal Hemorrhage General Management:  Iv acess and fluid resuscitation  Do not overtransfuse (hemoglobin ~ 8 g/dL)  Antibiotic prophylaxis Specific therapy:  Pharmacological therapy: terlipressin, somatostatin and analogues, vasopressin + nitroglycerin  Endoscopic therapy: ligation, sclerotherapy  Shunt therapy: TIPS, surgical shunt General Management:  Iv acess and fluid resuscitation  Do not overtransfuse (hemoglobin ~ 8 g/dL)  Antibiotic prophylaxis Specific therapy:  Pharmacological therapy: terlipressin, somatostatin and analogues, vasopressin + nitroglycerin  Endoscopic therapy: ligation, sclerotherapy  Shunt therapy: TIPS, surgical shunt TREATMENT OF ACUTE VARICEAL HEMORRHAGE

9. Endoscopic Variceal Band Ligation  Bleeding controlled in 90%  Rebleeding rate 30%  Compared with sclerotherapy:  Less rebleeding  Lower mortality  Fewer complications  Fewer treatment sessions  Bleeding controlled in 90%  Rebleeding rate 30%  Compared with sclerotherapy:  Less rebleeding  Lower mortality  Fewer complications  Fewer treatment sessions ENDOSCOPIC VARICEAL BAND LIGATION

10. Transjugular Intrahepatic Portosystemic Shunt Hepatic vein Hepatic vein Portal vein Splenic vein Splenic vein Superior mesenteric vein TIPS THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT

11. Management of Uncomplicated Ascites Definition: Ascites responsive to diuretics in the absence of infection and renal dysfunction Sodium restriction  Effective in 10-20% of cases  Predictors of response: mild or moderate ascites, Urine Na excretion > 50 mEq/day Diuretics  Should be spironolactone-based  A progressive schedule (spironolactone  furosemide) requires fewer dose adjustments than a combined therapy (spironolactone + furosemide) Sodium restriction  Effective in 10-20% of cases  Predictors of response: mild or moderate ascites, Urine Na excretion > 50 mEq/day Diuretics  Should be spironolactone-based  A progressive schedule (spironolactone  furosemide) requires fewer dose adjustments than a combined therapy (spironolactone + furosemide) MANAGEMENT OF UNCOMPLICATED ASCITES

12. Diuretic Therapy Dosage  Spironolactone 100-400 mg/day  Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalemia develops  Increase diuretics if weight loss <1 kg in the first week and < 2 kg/week thereafter  Decrease diuretics if weight loss >0.5 kg/day in patients without edema and >1 kg/day in those with edema  Side effects  Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastia Diuretic Therapy Dosage  Spironolactone 100-400 mg/day  Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalemia develops  Increase diuretics if weight loss <1 kg in the first week and < 2 kg/week thereafter  Decrease diuretics if weight loss >0.5 kg/day in patients without edema and >1 kg/day in those with edema  Side effects  Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastia Management of Uncomplicated Ascites MANAGEMENT OF UNCOMPLICATED ASCITES: DIURETIC THERAPY

13. Early Diagnosis of SBP  Diagnostic paracentesis:  If symptoms / signs of SBP occur  Unexplained encephalopathy and / or renal dysfunction  At any hospital admission  Diagnosis based on ascitic fluid PMN count >250/mm 3  Diagnostic paracentesis:  If symptoms / signs of SBP occur  Unexplained encephalopathy and / or renal dysfunction  At any hospital admission  Diagnosis based on ascitic fluid PMN count >250/mm 3 Rimola et al., J Hepatol 2000; 32:142 EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

14. Treatment of Spontaneous Bacterial Peritonitis  Recommended antibiotics for initial empiric therapy  i.v. cefotaxime, amoxicillin-clavulanic acid  oral nofloxacin (uncomplicated SBP)  avoid aminoglycosides  Minimum duration: 5 days  Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of treatment  Recommended antibiotics for initial empiric therapy  i.v. cefotaxime, amoxicillin-clavulanic acid  oral nofloxacin (uncomplicated SBP)  avoid aminoglycosides  Minimum duration: 5 days  Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of treatment Rimola et al., J Hepatol 2000; 32:142 TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)

15. Type C Hepatic Encephalopathy is the Encephalopathy of Cirrhosis  Neuropsychiatric complication of cirrhosis  Results from spontaneous or surgical / radiological portal-systemic shunt + chronic liver failure  Failure to metabolize neurotoxic substances  Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis)  Neuropsychiatric complication of cirrhosis  Results from spontaneous or surgical / radiological portal-systemic shunt + chronic liver failure  Failure to metabolize neurotoxic substances  Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis) TYPE C HEPATIC ENCEPHALOPATHY IS THE ENCEPHALOPATHY OF CIRRHOSIS

16. StageMental stateNeurologic signs 1Mild confusion: limited attention Incoordination, tremor, span, irritability, inverted sleep impaired handwriting pattern 2Drowsiness, personality changes,Asterixis, ataxia, dysarthria intermittent disorientation 3Somnolent, gross disorientation,Hyperreflexia, muscle marked confusion, slurred speech rigidity, Babinski sign 4Coma No response to pain, decerebrate posture 1Mild confusion: limited attention Incoordination, tremor, span, irritability, inverted sleep impaired handwriting pattern 2Drowsiness, personality changes,Asterixis, ataxia, dysarthria intermittent disorientation 3Somnolent, gross disorientation,Hyperreflexia, muscle marked confusion, slurred speech rigidity, Babinski sign 4Coma No response to pain, decerebrate posture Stages of Hepatic Encephalopathy STAGES OF HEPATIC ENCEPHALOPATHY

17. Hepatic Encephalopathy Is A Clinical Diagnosis  Clinical findings and history important  Ammonia levels are unreliable  Ammonia has poor correlation with diagnosis  Measurement of ammonia not necessary  Number connection test  Slow dominant rhythm on EEG  Clinical findings and history important  Ammonia levels are unreliable  Ammonia has poor correlation with diagnosis  Measurement of ammonia not necessary  Number connection test  Slow dominant rhythm on EEG HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS

18. Hepatic Encephalopathy Pathogenesis Bacterial action Protein load Bacterial action Protein load Failure to metabolize NH 3 NH 3 Shunting GABA-BD receptors GABA-BD receptors Toxins PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY

19. Treatment of Hepatic Encephalopathy  Identify and treat precipitating factor  Infection  GI hemorrhage  Prerenal azotemia  Sedatives  Constipation  Lactulose (adjust to 2-3 bowel movements/day)  Protein restriction, short-term (if at all)  Identify and treat precipitating factor  Infection  GI hemorrhage  Prerenal azotemia  Sedatives  Constipation  Lactulose (adjust to 2-3 bowel movements/day)  Protein restriction, short-term (if at all) TREATMENT OF HEPATIC ENCEPHALOPATHY

20. Actions of Lactulose Lactulose Lactic acid Decreased pH NH 3 Urease-producing bacteria Increase cathartic effect NH 3 NH 4 + ACTIONS OF LACTULOSE