The Arlene Berry Case

Arlene Berry died suddenly and unexpectedly at the age of 41, less than 24 hours after being admitted to the Kirkland & District Hospital  on May 23rd of 2000. She had presented initially with "flu-like symptoms with alterations in GI function that have since been thoroughly researched and computer traced to liver encephalopathy due to liver impairment, or acute liver failure. On-line Medical Dictionary Description:Acute Liver Failure

Coagulopathy and altered mental status define the syndrome of acute liver failure. Because acute liver failure is rare, related data have been sparse and the mechanisms by which infection triggers hepatic encephalopathy require further investigation. Studies have suggested that viral hepatitis is the most common underlying cause of this condition. Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure with Tylenol overdoses linked to acute liver failure. Patients with ALF have increased susceptibility to infections. The predominant bacterial pathogens include staphylococci aureus, coagulase-negative staphylococci, streptococci species and coliform organisms (Escherichia coli and pseudomonas aeruginosa). Compare: coagulase-negative staphylococci in the presence of heparin.

Clinically, patients with acute hepatitis may be completely asymptomatic and without jaundice. The usual definition of acute liver failure is the onset of altered mental status (hepatic encephalopathy) and coagulation abnormalities after an illness of less than 26 weeks, although many would use a shorter interval such as 8 to 10 weeks. The most common cause of ALF is related to acetaminophen toxicity, drug reactions, and infection, such as from antibiotic-resistant staphylococci (Staphylococcal Infections), aggrevated by untreated necrotizing enterocolitis, with possible azotemia attributed to untreated or inadequately treated dehydration.

Postoperative infections, ranging from stitch abscesses to extensive wound involvement, commonly are due to staphylococci. Such infections may appear within a few days or several weeks after surgery; they are likely to be delayed in onset if the patient received antibiotics at the time of surgery. O'Grady (1993; London): Dr. Wu's Liver diseases
classification: (encephalopathy appears ~wks within or after the onset of the first symptoms)
Hyperacute liver failure ( within 1 week),
acute liver failure( 2 to 4 weeks) and
subacute liver failure ( 5 to 12 weeks).
survival rate with medical management :

Drugs. Numerous medications can damage the liver, ranging from mild, asymptomatic alteration in liver chemistries to hepatic failure and death. Liver toxicity may or may not be dose-related.

There is howerver, further evidence pointing to possible hypoxic ischemic encephalopathy. Further, HIE is similar to stroke syndromes in adults. There is a distinct pattern of cognitive impairment with respect to these findings, including possible hyponatremic injury that must also be addressed.

Mechanisms of Injury;

Hypoxic Ischemic= lack of oxygen
Encephalopathy = damage to brain
(from various causes, i.e., heart attack, drug overdoses, etc.)
Definition:

The findings suggest related heart, liver and kidney failure associated with ANOREXIA in which metabolic causes via liver, kidney, lung, and heart relationship, suggestive of a multiple organ dysfunction syndrome associated with diseases of the genitourinary system, liver or biliary system, and intestinal system related to recent infection, prolonged antibiotic therapy, and having had a recent surgical or medical procedure, including toxins that I will ascerbically equate with SIRS,an excessive inflammatory response triggered by overproduction of cytokines in which systemic manifestations of the inflammatory response follow a similar timecourse and include low grade fevers, chills, and a flu-like malaise that is consistent with that of the deceased, suggestive of possible staphylococcal toxic shock syndrome, as evidenced by GI illness, Central nervous system: disorientation or alteration in consciousness but no focal neurological signs at a time when fever and hypotension are absent, leukocytosis, elevated prothrombin time, and coagulopathy.

Presents subacutely rather than acutely. Thrombocytosis (rather than thrombocytopenia) is common.

Electrolyte levels may indicate hypokalemia, hyponatremia, with evidence of increased intracranial pressure, increased work breathing (acute respiratory distress syndrome or pulmonary edema), and intracranial hypertension are all associated with toxic shock syndrome.

Toxic shock syndrome is among infectious diseases characterized by rashes as early diagnostic clues.

The hallmark of this condition is the creation of a proinflammatory state, and is associated with hypoperfusion, including sepsis, and shock (= cordiovascular collapse). Shock is a life threatening condition with a variety of possible causes, including loss of fluid and electrolytes from the gut.

Predisposing factors in hepatic encephalopathy include a history of blood in stools (black or bloody stools), opiate use, infection, GI bleeding, dehydration or electrolyte abnormalities. The disorder may also be triggered by any condition that results in alkalosis (alkaline pH). Perhaps the most common predisposing factor is gastrointestinal bleeding, which leads to an increase in the production of ammonia and other nitrogenous substances which are then absorbed.Ammonia is toxic to the CNS and is one of the causes of hepatic encephalopathy.

Compare: Acidosis and Alkalosis, with evident etiology to support this finding. But there is much more to this dillema based on additional findings.

In people with otherwise stable liver disorders, hepatic encephalopathy may be triggered by episodes of gastrointestinal bleeding, excessive dietary protein, or electrolyte abnormalities, especially decrease in potassium, which may result from vomiting, or iatrogenic causes, i.e. treatments, procedures.

Blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

The disorder may also be triggered by any condition that results in alkalosis (alkaline blood pH), low oxygen levels in the body, use of medications that suppress the central nervous system, infections including viral hepatitis, bile duct obstruction, surgery, or any coincidental illness. Compare: Metabolic alkalosis

The liver has a limited number of responses to an infinite number of insults: inflammation, degeneration, necrosis, fibrosis, cirrhosis.

Progress from onset of symptoms to liver failure in as early as 2-3 weeks - usually viral or toxic. Compare: eMedicine - Hepatic Failure : Article by Blake A Jones, MD.

Blood alkalosis inhibits the transport of oxygen to tissues and organs, constricts the blood vessels, and lowers overall circulating blood volume.

A blood pH above 7.4 shows impairment, and above 7.5 there is significant impairment almost no oxygen transport at all.

In people with otherwise stable liver disorders, hepatic encephalopathy may be triggered by episodes of gastrointestinal bleeding, excessive dietary protein, or electrolyte abnormalities (especially decrease in potassium, which may result from vomiting or treatments.

There is a close proximity to Arlene's symptoms to the common but unpleasant side effects of her post-operative course of radiation therapy, i.e. radiation injuries and/or the concomitant effects of her medication regime suggestive of iatrogenic hepatic encephalopathy. She presented to the ER with a hepatitis-like picture or an acute variant thereof believed to have been triggered by inflamation of the porta area, that is consistent with portal-systemic encephalopathy, or portal vein obstruction. Further, Blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

A possible cholestatic reaction to amoxicillin (antibiotic), or radiation induced bile duct injury cannot be ruled out. Upon admission to hospital on May 23rd of 2000, her symptoms were flu-like with bilious vomit, (bile is the bitter, alkaline, brownish-yellow/greenish-yellow or yellow-green fluid secreted by the liver, stored in the gallbladder, and discharged into the duodenum that is consistent with a duodenal or small bowel obstruction. She later went into coma following the administration of a totally contraindicated brain damaging, neurotoxic, anti-psychotic drug by the name of Stemetil (prochlorperazine). Compare: hepatic coma. There was coffee-ground vomit following administration of the drug Stemetil (prochlorperazine), a high risk antiemetic antipsychotic drug believed to have been responsible for exascerbating her condition.

acute form that develops over a period of days.
Compare: SIGNS AND SYMPTOMS THAT MAY BE ASSOCIATED WITH HEPATITIS C

FHF is a term used to describe the development of coagulopathy and encephalopathy as a result of acute hepatic decompensation within 8 weeks from the onset of illness, and this seems to fit the bill with absolute precision.

Other considerations include:

Mechanism of Drug Induced Hepatotoxicity
Hepatitis is an inflammatory process in the liver. It has multiple causes including viruses, drugs and alcohol being the most common.
Toxic & -induced hepatitis,
THE MERCK MANUAL, Sec. 4, Ch. 43, And The Liver.

The principal mechanism underlying cholestasis relates to an interference with bile or bile-acid secretion by oxidant stress and other injurious processes affecting the function of cell organelles Major causes include those of autoimmune, toxic (drug induced), viral, and mechanical bile duct stricture, bile duct obstruction, nature, as well as inborn errors, bile acid synthesis and phospholipids transport.
Compare: liver cirrhosis, biliary.

Compare also Hepatorenal Syndrome-->=bile nephrosis, in which nausea, vomiting, headaches, blood in vomit, blood in stools, abdominal swelling, decrease urine production are all prominant findings.

Cholestasis reflects bile secretion failure. pathologic effects of cholestasis reflects backup of bile constituents. Intrahepatic cholestasis is favored by symptoms of hepatitis, recent use of potentially cholestatic drugs or signs of hepatocellular disease, i.e ascites.   Cholestasis  reflects bile secretion failure in which  reactions are most often due to billiary obstruction from intra-abdominal complications,  or to drugs prescribed postoperatively.

In hepatomegally, the normal liver has a rubbery-soft, smooth edge. This consistency is often maintained due to acute hepatitis, fatty infiltration, passive congestion, and early biliary obstruction.

======================== COMPARE: Postgraduate Medicine: Hepatic encephalopathy