Liver diseases 1

1. Liver diseases 1

2. Blood supply • Liver receives 25% of resting cardiac output. • Blood enters via • hepatic artery (25%) & portal vein (75%). • carries blood from gut • rich in absorbed nutrients • portal flow increases after meals • Blood leaves via • hepatic vein • Also leaving liver • hepatic ducts • carry bile to gall bladder

3. Normal Situation Systemic Circulation Urea Collateral Splanchnic Circulation GIT Bacteria Protein NH3

4. Presentations of Liver Disease • 􀂄Jaundice • 􀂄Hepatomegaly +/-splenomegaly • 􀂄Abnormal Liver Chemistries (ALT, AST, Alkaline phosphatase, Bilirubin) • 􀂄Portal hypertension (ascites, bleeding from esophageal varices, encephalopaty, thrombocytopenia) • 􀂄Viral markers for hepatitis B or C. • 􀂄Right Upper Quadrant pain

5. Liver Disease: History • Anorexia -related to change in taste/smell • 􀂄Weight loss ->10 lbs. (Malignancy?) • 􀂄Fatigue, mild fever, myalgia –viral hepatitis • 􀂄Chills, fever, biliary tract disease • 􀂄Pruritus –cholestatic liver disease

6. Major Determinants of Disease • toxic accumulations of: • metabolic waste (especially ammonia & bilirubin) • drugs & toxins • endogenous hormones (especially estrogen) • bleeding, associated with a deficiency of coagulation factors. • edema, associated with a deficiency of albumin. • failure to absorb intestinal fat because of a deficiency of bile acids.

7. Viral hepatitis is a common disease. • Cirrhosis is the final endpoint for many liver diseases. • Portal HTN is the most important consequence of cirrhosis & can be associated with liver failure & severe hemorrhage. • Stones often form in the gallbladder & may pass into & obstruct the bile duct.

8. Liver function tests (LFTs) • enzymes • Lactic dehydrogenase (LDH) • Aspartateaminotransferase (AST) • Alanineaminotransferase (ALT) • Alkaline phosphatase (ALKP) • bilirubin • albumin • PT & PTT • viral antigens & antibodies • autoimmune antibodies

9. Synthetic Function • Albumin–12-15 gm/d normally synthesized Low albumin suggest advanced liver disease. • Prothrombin time (PT):deficiency ofCoagulation factors –I, II, V, VII, IX, X, XII, XIII produced in liver, suggest severe liver disease .

10. Jaundice Yellow skin and sclera (bilirubin > 2.8 mg/dl)

11. Jaundice Jaundice indicates one of four problems: 1. increased RBC breakdown . 2. failure of hepatocyte conjugation . 3. failure of hepatocyte excretion of conjugated bilirubin. into the bile canaliculi . 4. extrahepatic obstruction .

12. Liver impairment can cause : • Defects in Amino Acid Metabolism • Defects in Protein Synthesis • Defects in Carbohydrate Metabolism • Defects in Lipid Metabolism • Impaired Production of Clotting Factors • Impairment of Detoxification Functions

13. Portal Hypertension • What is Portal Hypertension? • Portal hypertension is a term used to describe elevated pressures in the portal venous system (a major vein that leads to the liver).

14. Symptoms • Gastrointestinal hemorrhage may be the initial presenting symptom of patients with portal hypertension. Those patients with more advanced liver disease often • present with ascites, hepatic encephalopathy , jaundice, coagulopathy,

15. Portal Hypertension: Causes • Portal hypertension may be caused by intrinsic liver disease, obstruction, or structural changes that result in increased portal venous flow or increased hepatic resistance.

16. Ascites • Ascites is the accumulation of an abnormal volume of fluid in the peritoneal cavity.

17. Pathophysiology of ascites • portal hypertension (increased pressure in the liver blood flow) as the main contributor. The basic principle is similar to the formation of edema due to an imbalance of pressure between inside the circulation (high pressure system) and outside, in this case, the abdominal cavity (low pressure space) Movement of fluid from high pressure system ( circulation) to low pressure space ( the abdominal cavity ) Accumulation of fluid in the peritoneal cavity(ascites )

18. Cirrhosis • Final, common end-stage for a variety of chronic liver diseases

19. The physical evidences of cirrhosis fall broadly into these categories: • 1. changes in liver size and consistency • 2. evidence of portal hypertension • 3. evidence of impaired protein synthesis • 4. evidence of nutritional deficiencies, particularly of the fat soluble vitamins • 5. evidence of altered bilirubin metabolism (jaundice) • 6. evidence of impaired degradative abilities • 7. other associated phenomena

20. Progressive • Irreversible • Incurable • Causes of cirrhosis1. alcohol abuse2. viral hepatitis (B.C )3. Biliary obstructions a. Gallstone b. cystic fibrosis

21. Hepatic Encephalopathy • This complex neuromuscular/neuropsychiatric syndrome occurs in severe liver disease, either late in chronic disease or as a presenting symptom of acute hepatic failure. Causes: • Build up of toxins (ammonia) as a result of poor hepatic function. • Accumulation of cytokines . • Fulminant hepatic failure . • Severe hepatocellular disease.

22. Neurologic disturbances of Hepatic Encephalopathy • Stage I: personality and mood changes, anxiety, mild confusion, disturbance of sleep/wake cycles; fine tremor, poor coordination, slurred speech, poor handwriting. • Stage II: moderate confusion, disorientation, lethargy, inappropriate behavior; primitive reflexes, dysarthria, rigidity. • Stage III: marked confusion, somnolence, incontinence; incoherent speech, hyperreflexia. • Stage IV: coma, which may initially respond to noxious stimuli and then not .

23. Liver failurea) Acute hepatic failure • Types of acute hepatic failure: • Fulminant (hyperacute) hepatic failure ( FHF ): (FHF) is a syndrome of abrupt onset (fulminant explosive), characterized by progressively severe encephalopathy occurring within 7–14 days of the onset of jaundice. FHF is the result of massive hepatocellular necrosis, i.e. death of the liver parenchyma, or other severe functional impairment. •

24. Etiology of FHF In the UK, paracetamol (acetaminophen) poisoning is the most common cause. Many other drugs may cause FHF anaesthesia with halothane being a well-recognized cause, but monoamine oxidase inhibitors (MAOIs), antiepileptics and antimicrobial agents may also be involved. FHF may also occur in Wilson’s disease, Reye’s syndrome and pregnancy and following solvent ingestion or ‘glue sniffing’.

25. Chronic liver failure Chronic liver failure may be the consequence of any chronic liver disease .However,some patients show evidence of raised serum transaminases ( ALT , AST ) or persistent viral hepatitis discovered by chance during investigations . (e.g. when donating blood), without ever showing symptoms or progressing to liver failure. Chronic progressive liver disease always leads to portal hypertension, resulting in ascites or bleeding oesophagealvarices and encephalopathy Cirrhosis frequently develops insidiously.