Clinical cases and Situational tasks

58. A 45-year-old male with history of hepatitis C and now cirrhosis of the liver is brought to the emergency center by family members for acute mental status changes. The family reports that the patient has been very disoriented and confused over the last few days and has been nauseated and vomiting blood. The family first noticed disturbances in his sleep pattern followed by alterations in his personality and mood. On examination, he is disoriented with evidence of icteric sclera. His abdomen is distended with a fluid wave appreciated. He has asterixis and hyperreflexia on neurologic exam. His urine drug screen and ethyl alcohol (EtOH) screen are both negative. A blood ammonia level was noted to be elevated, and all other tests have been normal. What is the most likely cause of the patient’s symptoms? What is asterixis? What was the likely precipitating factor of the patient’s symptoms?

Answer: Diagnosis: Hepatic encephalopathy likely secondary to elevated ammonia levels. Asterixis: Nonspecific to hepatic encephalopathy. Nonrhythmic asymmetric tremor with loss of voluntary control of extremities while in a sustained position. It is also known as “liver flap.” Precipitating factor: Increased nitrogen load from upper gastrointestinal bleed.

Cirrhosis is a chronic condition of the liver with diffuse parenchymal injury and regeneration leading to distortion of the liver architecture and increased resistance of blood flow through the liver. The patient usually manifests malaise, lethargy, palmar erythema, ascites, jaundice, and hepatic encephalopathy in the late stages. Toxins accumulating in the blood stream affect the patient’s mental status. The most common etiologies of cirrhosis are toxins such as alcohol, viral infections such as hepatitis B or C infection, or metabolic diseases in children (Wilson disease, hemochromatosis, or α1-antitrypsin deficiency). Treatment depends on the exact etiology, although the common therapy includes avoidance of liver toxins, salt restriction, and possibly procedures to reduce the portal pressure.

59. A 20-year-old female was brought to the emergency department after being found on the dormitory room floor nauseated, vomiting, and complaining of abdominal pain. Her friends were concerned when she did not show up for a biochemistry final at the local university. The patient had been under a lot of stress with finals, a recent breakup with a boyfriend, and trying to find a job. In the dormitory room, one of her friends noticed an empty bottle of Tylenol (acetaminophen) near the bed with numerous pills lying on the ground near their friend. On arrival to the emergency department, the patient was found to be in moderate distress and vomiting. The patient was quickly assessed, and laboratory work was obtained. Patient had a hypokalemia noted on electrolytes and elevated liver enzymes. Her white blood cell count was normal. Her urine drug screen was negative, and her acetaminophen blood level was above 200 μg/mL. The emergency department physician prescribes oral N-acetylcysteine to help prevent toxicity from the acetaminophen. What is the pathophysiology of the liver toxicity?What is the biochemical mechanism whereby the N-acetylcysteine helps in this condition?

Answer: Acetaminophen is metabolized via the cytochrome P450 enzymes into a deleterious product N-acetyl benzoquinoneimine, an unstable intermediate, which causes arylated derivatives of protein, lipid, ribonucleic acid (RNA), and deoxyribonucleic acid (DNA), causing destruction of these compounds. Because the liver has high levels of cytochrome P450 enzymes, it is the major organ affected by acetaminophen overdose.

Biochemical mechanism of N-acetylcysteine: As glutathione is used to conjugate the acetaminophen toxic metabolite, the antidote Nacetylcysteine helps to facilitate glutathione synthesis by increasing the concentrations of one of the reactants of the first synthetic step.

The patient described has all the initial signs of a deliberate overdose of acetaminophen. Normally acetaminophen is cleared by conjugation with either glucuronic acid or sulfate followed by excretion. Metabolism also takes place, producing an active intermediate capable of binding tissue macromolecules. These conjugative and metabolic pathways involve a number of enzymes that may themselves be compromised to such an extent that the threshold for the concentration that constitutes an overdose is substantially lowered. More typically, overdose concentrations are the result of deliberate ingestion, as in this clinical case, or accidental ingestion, often involving either a child who finds a bottle of acetaminophen and consumes its contents or a disoriented elderly person who loses track of how many tablets have been consumed. Usually, the acetaminophen serum level is drawn and plotted on a nomogram to determine the possibility of hepatic damage. Hepatocyte necrosis with clinical manifestations of nausea and vomiting, diarrhea, abdominal pain, and shock may ensue. Few survivors of an overdose have long-term hepatic disease. The initial therapy is gastric lavage, activated charcoal, supportive care, and administration of N-acetylcysteine.

60. A 45-year-old female presents with hypercholesterolinemia, ultrasound evidence of gallstones, and recurrent symptoms of gallbladder disease. What factors would you need to consider to assess the need for cholecystectomy? What are gallstones made of?

Answer: Surgical candidates: Frequent and severe attacks, previous complications from gallstones, presence of underlying condition predisposing the patient to increased risk of gallbladder disease. Components of gallstones: Cholesterol, calcium bilirubinate, and bile salts.

This individual fits the “classic” patient with gallbladder disease: female middle-aged, overweight. The gallbladder acts to store bile salts produced by the liver. The gallbladder is stimulated to contract when food enters the small intestine; the bile salts then travel through the bile duct to the ampulla of Vater into the duodenum. The bile salts act to emulsify fats, helping with the digestion of fat. Gallstones form when the solutes in the gallbladder precipitate. The two main types of stones are cholesterol stones and pigmented stones. Cholesterol stones are usually yellow-green in appearance and account for approximately 80 percent of gallstones. Pigmented stones are usually made of bilirubin and appear dark in color. Patients may have pain from the gallstones, usually after a fatty meal. The pain is typically epigastric or right upper quadrant and perhaps radiating to the right shoulder. If the gallbladder becomes inflamed or infected, cholecystitis can result. The stones can also travel through the bile duct and obstruct biliary flow leading to jaundice (yellow color or the skin), or irritate the pancreas and cause pancreatitis.

61. A 26-year-old female at 35 weeks gestation with generalized pruritus without a rash and slightly elevated liver transaminases and bilirubin. What is the patient’s likely diagnosis? What are treatment options? What is the cause of the patient’s generalized itching?

Answer: Diagnosis: Cholestasis of pregnancy. Cholestasis of pregnancy is a condition in which the normal flow of bile from the gallbladder is impeded, leading to accumulation of bile salts in the body. Generalized itching and, possibly, jaundice may result. It is speculated that the hormones such as estrogen and progesterone, which are elevated in pregnancy, cause a slowing of the gallbladder function, leading to this disorder. Uncomplicated cholestasis is usually diagnosed clinically by generalized itching in a pregnant woman, usually in the third trimester without a rash. Elevated serum levels of bile salts can help to confirm the diagnosis. Elevated bilirubin levels or liver transaminase enzymes may also be seen. The usual treatment includes antihistamine medications for the itching. Some experts recommend ursodeoxycholic acid, a naturally occurring bile acid that seems to improve liver function and may reduce the serum bile acid concentration. More severe cases may require bile salt binders such as cholestyramine or corticosteroids. Treatment options: Oral antihistamines, cholestyramine, ursodeoxycholic acid. Etiology of generalized itching: Increased serum bile salts and accumulation of bile salts in the dermis of the skin.

62. A 18-year-old male with sickle cell anemia develops severe right upper-abdominal pain radiating to his lower right chest and his right flank 36 hours prior to admission to the ER. Twelve hours following the onset of pain, he began to vomit intractably. In the past year he has had several episodes of mild back and lower extremity pain that he attributed to mild sickle cell crises. He reported that the present pain was not like his usual crisis pain. He also reports that his urine is the color of iced tea and his stool now has a light clay color. On examination, his temperature is slightly elevated, and heart rate is rapid. He is exquisitely tender to pressure over his right upper abdomen. The sclerae of his eyes are slightly yellowish in color. What is the most likely cause of this patient’s symptoms?

Answer: Although a cholesterol-rich gallstone cannot be completely ruled out with the given information, because the patient has experienced several mild sickle cell crises that are accompanied by increased red blood cell destruction, his symptoms are consistent with a gallstone caused by precipitation of calcium salt of bilirubin. Large quantities of bilirubin can overwhelm the ability of the liver to convert it to the more soluble diglucuronide conjugate. As a consequence, the more insoluble unconjugated form enters the bile and is easily precipitated in the presence of calcium ion. If a large stone forms, it can obstruct the bile duct and result in the symptoms exhibited by the patient.

63. A 45-year-old male with history of hepatitis C and now cirrhosis of the liver is brought to the emergency center by family members for acute mental status changes. The family reports that the patient has been very disoriented and confused over the last few days and has been nauseated and vomiting blood. The family first noticed disturbances in his sleep pattern followed by alterations in his personality and mood. On examination, he is disoriented with evidence of icteric sclera. His abdomen is distended with a fluid wave appreciated. He has asterixis and hyperreflexia on neurologic exam. His urine drug screen and ethyl alcohol (EtOH) screen are both negative. A blood ammonia level was noted to be elevated, and all other tests have been normal. What is the most likely cause of the patient’s symptoms? What was the likely precipitating factor of the patient’s symptoms?

Answer: Diagnosis: Hepatic encephalopathy likely secondary to elevated ammonia levels. Precipitating factor: Increased nitrogen load from upper gastrointestinal bleed. Cirrhosis is a chronic condition of the liver with diffuse parenchymal injury and regeneration leading to distortion of the liver architecture and increased resistance of blood flow through the liver. The patient usually manifests malaise, lethargy, palmar erythema, ascites, jaundice, and hepatic encephalopathy in the late stages. Toxins accumulating in the blood stream affect the patient’s mental status. The most common etiologies of cirrhosis are toxins such as alcohol, viral infections such as hepatitis B or C infection, or metabolic diseases in children (Wilson disease, hemochromatosis, or α1-antitrypsin deficiency). Treatment ndepends on the exact etiology, although the common therapy includes avoidance of liver toxins, salt restriction, and possibly procedures to reduce the portal pressure.