Cirrhosis and Ascites. Thomas S. Foster, Pharm.D. Integrated Therapeutics PHR 961

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1 Cirrhosis and Ascites Thomas S. Foster, Pharm.D. Integrated Therapeutics PHR 961

2 Overview Liver weighs about 3 pounds and is the largest organ in the body. It is located in the upper right side of the abdomen, below the ribs. Chronic diseases cause the liver to become permanently injured and scarred--cirrhosis.

3 Cirrhosis-Definition Literally, yellow liver condition, frequently caused by chronic alcoholism, characterized in its early stages by enlargement of the liver caused by the appearance of fatty and fibrous tissue. Late stages it becomes Laënnec's cirrhosis, or "hobnail liver", in which normal liver lobules are replaced by nodules, sometimes containing fat, separated by strands of fibrous tissue, and the liver contracts. The condition can cause hypertension, impaired blood flow through the liver, serous fluid flooding of the abdominal cavity, and ultimately death.

4 Liver Functions Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Acting as the body's largest chemical factory, it has thousands of functions including: the production of clotting factors, blood proteins, bile and more than a thousand different enzymes the metabolism of cholesterol the storage of energy (glycogen) to fuel muscles maintenance of normal blood sugar concentration the regulation of several hormones and the detoxification of drugs and poisons including alcohol. Liver disease can cause widespread disruption of body function. While many liver diseases can occur, one of the most important is cirrhosis.

5 Causes of Liver Disease There are a number of conditions that can lead to cirrhosis: excessive intake of alcohol (most common) types B, C and D of chronic viral hepatitis, inherited or congenital diseases -- hemochromatosis Wilson s Dx-- abnormal accumulation of copper in the liver and other organs due to the decreased excretion of copper from the liver. Alpha1 antitrypsin deficiency--inherited absence of a specific enzyme in the liver. Glycogen storage disease --inability to properly utilize sugars. Autoimmune hepatitis prolonged obstruction or other diseases of the bile ducts (biliary cirrhosis, sclerosing cholangitis) prolonged exposure to environmental toxins some forms of heart disease (cardiac cirrhosis) severe reaction to drugs schistosomiasis (parasitic infection)

6 Consequences Scar tissue that forms in cirrhosis harms the structure of the liver, blocking the flow of blood through the organ. Loss of normal liver tissue slows the processing of nutrients, hormones, drugs, and toxins by the liver. Also slowed is production of proteins and other substances made by the liver.

7 Consequences--Liver Disease Chronic disease of the liver may modify the body's responses to a variety of illnesses. Abnormal function of the liver in cirrhosis may: affect the dose of medicine required in the treatment of other conditions affect the treatment of diabetes alter response of the body to infection alter tolerance for surgical procedures Patients with cirrhosis are particularly prone to develop fatal bacterial infections, kidney malfunctions, stomach ulcers, gallstones, a type of diabetes and cancer of the liver.

8 Hepatomegaly

9 Liver in Alcoholic Cirrhosis

10 Liver Disease: Contrasting Path

11 Symptoms Weight loss, malnutrition, fatigue, easy bruising (caused by reduced levels of factors II, VII, IX, and X), jaundice, encephalopathy, pruritus, edema, and ascites. The patient may also have GI bleeding from esophageal varices.

12 Laboratory Analysis Laboratory evaluation may show normal liver enzymes. Low serum levels of total protein and albumin. Anemia and thrombocytopenia may also be present. Blood ammonia levels may be elevated, but these correlate poorly with clinical manifestations of coma. Electrolyte abnormalities include hyponatremia, hypokalemia, and water overload Concomitant acidosis or alkalosis.

13 Symptoms People with cirrhosis often have few symptoms at first. The two major problems that eventually cause symptoms are loss of functioning liver cells and distortion of the liver caused by scarring. The person may experience fatigue, weakness, and exhaustion. Loss of appetite is usual, often with nausea and weight loss. As liver function declines, less protein is made by the organ. Less of the protein albumin is made, which results in water accumulating in the legs (edema) or abdomen (ascites). A decrease in proteins needed for blood clotting makes it easy for the person to bruise or to bleed.

14 Symptoms--Late Disease In the later stages of cirrhosis, jaundice (yellow skin) may occur, caused by the buildup of bile pigment that is passed by the liver into the intestines. Cirrhosis- people experience intense itching due to bile products that are deposited in the skin. Gallstones often form in persons with cirrhosis because not enough bile reaches the gallbladder.

15 Consequences The liver of a person with cirrhosis also has trouble removing toxins, which may build up in the blood. These toxins can dull mental function and lead to personality changes and even coma (encephalopathy). Early signs of toxin accumulation in the brain may include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleeping habits.

16 Portal Circulation A serious problem for people with cirrhosis is pressure on blood vessels that flow through the liver. Normally, blood from the intestines and spleen is pumped to the liver through the portal vein. In cirrhosis, this normal flow of blood is slowed, building pressure in the portal vein (portal hypertension). This blocks the normal flow of blood, causing the spleen to enlarge. So blood from the intestines tries to find a way around the liver through new vessels.

17 Development of Varices Some of these new blood vessels become quite large and are called varices. These vessels may form in the stomach and esophagus They have thin walls and carry high pressure. There is great danger that they may break, causing a serious bleeding problem in the upper stomach or esophagus.

18 Diagnosis Computerized Axial Tomography (CAT) scan, ultrasound, and the radioisotope liver/spleen scan. Biopsy- putting a needle through the skin to take a sample of tissue from the liver. In some cases, cirrhosis is diagnosed during surgery The liver also can be inspected through a laparoscope, a viewing device that is inserted through a tiny incision in the abdomen.

19 Treatment Strategy Treatment of cirrhosis is aimed at stopping or delaying its progress, minimizing the damage to liver cells, and reducing complications. In alcoholic cirrhosis, for instance, the person must stop drinking alcohol to halt progression of the disease.

20 Medication Treatment Overview Medications may be given to control the symptoms of cirrhosis, such as itching. Edema and ascites are treated by reducing salt in the diet. Diuretics are used to remove excess fluid and to prevent edema from recurring. Diet and drug therapies can help to improve the altered mental function that cirrhosis can cause. For instance, decreasing dietary protein results in less toxin formation in the digestive tract. Laxatives such as lactulose may be given to help absorb toxins and speed their removal from the intestines.

21 Additional Considerations The two main problems in cirrhosis are liver failure and bleeding caused by portal hypertension. Blood pressure medication, such as a beta blocker, to treat the portal hypertension. If the patient bleeds from the varices of the stomach or esophagus, a sclerosing agent administered through a flexible tube (endoscope) that is inserted through the mouth and esophagus. In critical cases, a liver transplant or another surgery (such as a portacaval shunt) that is sometimes used to relieve the pressure in the portal vein and varices.

22 Ascites Pathologic accumulation of serous fluid within the abdomen. Caused by decompensated liver disease (alcohol- and virus-related cirrhosis), heart failure, abdominal carcinomatosis, tuberculosis, and pancreatic disease. Cirrhosis is the cause for the most number of cases of ascites.

23 Acute Management Clean bowels with enemas. Neomycin 4 to 6 g PO QD in divided doses to reduce bacterial toxins. Lactulose 30 to 45 g PO TID to produce two or three loose stools per day. Limit total protein intake to 20 to 40 g/day. Vitamin K 5 to 10 mg/day for 2 or 3 days may help coagulation. Potassium supplements may be used for hypokalemia. Potassium-sparing diuretics such as spironolactone 100 to 300 mg/day divided into 2 or 3 doses

24 Ascites Treatment Restricting sodium intake and the promotion of natriuresis with oral diuretics. Combinations of furosemide and spironolactone - optimal for promoting sodium excretion and sparing potassium. Doses should be titrated to a maximum of 400 mg/day and 160 mg/day of spironolactone and furosemide respectively. Other therapies include portal shunting and liver transplantation.

25 Paracentesis for Ascites Therapeutic paracentesis with the removal of 5 or more Liters is indicated if the patient presents with early satiety or shortness of breath. Give 40 g of albumin IV to prevent hyponatremia and renal failure.

26 Case Study TB is a 66 yowm seen in the emergency room complaining of abdominal pain, nausea and vomiting. He had been binging on alcohol for three days after being released from his job as a result of a merger deal at his company. He complains of continued thirst and frequent urination and has had blood in his stool and has vomited red tinged material

27 PM and Social History 15 year IDDM Drug Abuse(alcohol, cocaine, marijuana Chronic diarrhea 32 pound weight loss over 5 months 1 PPD-35 years alcohol- 1-2 six packs/day and binge on bourbon

28 Medication History NPH 20 U q AM and PM Regular Insulin 5 U qam and PM Cimetidine 400 p.o. tid Inderal 80 mg. q AM Allergies: None

29 Physical Exam Gen: Somewhat disoriented and thin man(130lbs) (usual weight lbs) jaundiced VS:BP 110/72,HR 88R, T 37.0C,RR25, HEENT:sclera anicteric,poor dentition,foul breath Abd: mid-epigastric pain,liver enlarged/palp 6 cm Rect: guiac-pos Ext: amputation-rl, ulcers on lf leg Neuro: uncooperative, some asterixis in hands

30 Lab Tests Na-133 K-3.2 Cl-104 HCO3-29 BUN-7.14 Cr-3.3 Hct-25 Hgb-9.8 LKCs-12.5 AST-300 ALT-230 Alk Phos- 180 Alb 1.9 T Bili-1.5 Glu-270 Ca-6.5 PO4-3.5 Trig-286 Amylase-370 PT-16/11

31 Problem List GI Bleed-Variceal Bleed Alcoholism with Cirrhosis PUD IDDM Malnutrition Altered Mental Status

32 Treatment Strategy Hepatic Problems Renal Problems Central Nervous System Problems

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