Cirrhosis and Its Complications Catch This Liver Scarring Problem Early, Because Its Effects Can Be Life-Threatening

Cirrhosis and Its Complications Catch this liver scarring problem early, because its effects can be life-threatening

By Scott R. Snyder, BS, NREMT-P, Sean M. Kivlehan, MD, MPH, NREMT-P, & Kevin T. Collopy, BA, FP-C, CCEMT-P, NREMT-P, WEMT

This month’s CE article looks at cirrhosis and its complications. In an attempt to best understand the signs and symptoms and progression of this disease, we will review the anatomy, physiology and pathophysiology of the liver and cirrhosis and the clinical manifestations of the disease and its complications.

ANATOMY OF THE LIVER The liver is the largest visceral organ in the body, and the majority of its mass is located in the upper right abdominal quadrant and extends into the upper left quadrant, lying directly below the diaphragm. It weighs about 3.3 lbs. (1.5 kg) in the average adult male.

The liver is encased in a tough, fi brous capsule (Glisson’s capsule) and covered by a layer of visceral peritoneum. It is held in place in the abdomen by several ligaments, including the falciform, round and coronary ligaments.

The gallbladder is a small, hollow, pear-shaped muscular sac that lies on the posterior surface of the liver. While not a true part of the liver, it works closely with the liver to store and secrete bile produced in the liver to aid digestion.

Blood Supply The liver is the largest blood reservoir in the body, receiving about 25% of the cardiac output. It is unique in that it has a double blood supply, receiving blood from both the hepatic portal vein and hepatic arteries. The hepatic portal vein delivers approximately 66% of the liver’s blood supply and carries venous blood drained from the spleen, gastrointestinal tract and other organs.1 It supplies nutrients and other essential chemicals absorbed by the digestive tract. The hepatic arteries supply oxygenated arterial blood to the liver, accounting for the remaining 33% of its blood fl ow.1

Hepatic Portal Circulation The splenic vein, gastric vein, esophageal vein, and inferior and superior mesenteric veins all feed into the portal vein and together comprise the hepatic portal circulation. Some of these blood vessels surround the esophagus and stomach, and the mesenteric veins contain products absorbed from digestion in the GI tract. The liver then performs its functions on this venous blood, processing useful products of digestion and fi ltering out toxins.

Liver Cells The liver is divided into approximately 100,000 individual lobules, the basic functional unit of the liver. Located in the lobules are the liver cells, or hepatocytes. Each hepatocyte is in contact with at least one of the sinusoid blood vessels that run between the portal and central veins. Another type of cells found in the liver are phagocytic macrophage cells called Kupffer cells. These are located in the sinusoids and engulf cell debris, pathogens and old or damaged red blood cells. Blood fl ows into the liver via the hepatic arteries and portal vein, then through the liver sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and drain into systemic circulation via the inferior vena cava. As such, the blood supplied to the liver is brought into contact with hepatocytes, which perform the majority of functions performed by the liver (Table 1). Bile produced by the hepatocytes drains into bile canaliculi and then the hepatic ducts on its way to storage in the gallbladder.

Simply put, the liver is like a large, blood-fi lled sponge that receives an ample supply of blood from both the hepatic arteries and the portal vein. For blood to move easily through this sponge and come into contact with hepatocytes and Kupffer cells, the functional units of the liver (the lobules) must be unobstructed and allow for proper fl ow. When this occurs, the liver can perform its required functions.

Table 1: Major Functions of the Liver

Digestive and metabolic functions Synthesis and secretion of bile; Storage and of glycogen and lipids; Regulation of blood glucose, fatty acids and amino acids; Storage of fat-soluble vitamins and minerals; Breakdown of hormones such as insulin and estrogen; Synthesis of angiotensinogen; Inactivation and absorption of toxins. Hematologic functions Synthesis of clotting factors; Removal of damaged and/or old RBCs and pathogens from circulation; Synthesis of plasma proteins.

© 2015 EMSWorld.com 1 EMSWORLD.com PHYSIOLOGY OF THE LIVER The liver provides numerous essential functions in the body; some Esophageal vein Liver with sources claim more than 200. These many roles can be broken down cirrhosis Esophageal varices into three basic categories: metabolic regulation; hematologic regulation; and synthesis and secretion of bile.1 Gastric varices Metabolic Regulation The liver plays a major role in the metabolic regulation of many body functions. All the blood leaving the absorptive areas of Portal the digestive tract (stomach, small and large intestines) enters vein Spleen the hepatic portal system and flows into the liver. This gives the Gastric liver the opportunity to extract ingested and absorbed nutrients, vein Superior mesenteric metabolic waste products and toxins from the blood before it vein enters systemic circulation via the hepatic veins.

Hepatocytes in the liver monitor the circulating levels of nutrients such as carbohydrates, amino acids and lipids (fats). Excess nutrients are removed from the blood and stored, and deficiencies can be Fran Milner, www.franimation.com corrected by tapping into stored reserves or synthesizing required nutrients. Excess glucose is stored in the liver as glycogen, and excess fatty acids as lipids, which can be utilized when deficiencies exist. In addition, fat-soluble vitamins such as A, D, K and E are absorbed by and stored in the liver, as are minerals such as iron and copper. Metabolic waste products and toxins are removed from circulation by the liver and deactivated, excreted and/or stored.

The liver plays a major role in the breakdown of not only toxins from the environment (for example, some hydrocarbons or poison from an ingested mushroom) but also in the metabolism of alcohol, drugs and medications. It is also responsible for the breakdown of hormones such as estrogen, testosterone and even insulin.

The liver plays an important role in blood pressure regulation via the synthesis of the inactive hormone angiotensinogen. When activated by renin (secreted by the kidney), angiotensinogen is converted to angiotensin, a hormone that will go on to increase blood pressure through a variety of functions.

Hematologic Regulation As blood passes through the liver, many important processes take place. Phagocytic cells in the liver remove cellular debris, damaged and/or old RBCs, and pathogens from circulation. In addition, cells in the liver synthesize plasma proteins. The major plasma protein in the human body is albumin. Albumin is a relatively large molecule and helps create and maintain the colloidal osmotic pressure of the blood that keeps fluid (plasma) in the vasculature and out of the surrounding tissues. The liver plays an important role in the production of numerous clotting factors required for normal function of coagulation as well as the complement protein components of the immune system.

SYNTHESIS AND SECRETION OF BILE Bile is synthesized by the liver, stored in the gallbladder and excreted into the proximal small intestine (duodenum). It is composed mostly of water (97%) and contains smaller amounts of bilirubin, ions and bile salts. Bile salts assist in the breakdown of lipids and absorption of fatty acids. The bile emulsifies fats entering the small intestine from the stomach, aiding in digestion.

Key functions of the liver described here (Table 2) are but a small fraction of the total number it provides. As such, any condition that damages the liver and prevents it from performing its role in the body can result in a serious, life-threatening condition. Cirrhosis of the liver and chronic liver failure is one such condition.

EPIDEMIOLOGY, ETIOLOGY AND PATHOPHYSIOLOGY The most recent data from the CDC reveals the overall mortality from chronic liver disease and cirrhosis in the United States in 2013 was 36,427 persons.2 The age groups with highest mortalities were 45–54 (8,785) and 55–64 (11,951); these accounted for more than half the deaths. Of persons who died of chronic liver disease and cirrhosis in 2013, 65% were male.2

Caucasians accounted for 87.4% of all deaths from chronic liver disease and cirrhosis.2 Caucasian males accounted for 57.2% of all deaths, while black males accounted for only 2.5%. Of the deaths in the U.S. in 2013 from liver disease and cirrhosis, alcoholic liver disease accounted for 49.8%, while other chronic liver disease and cirrhosis accounted for 50.2%.2

There are numerous etiologies of liver disease that can lead to cirrhosis, and the most common causes in the U.S. are hepatitis C, alcoholic liver disease and nonalcoholic liver disease. Together these three etiologies accounted for about 80% of patients on the liver transplant wait list between 2004–2013.3

While cirrhosis can be treated if identified in the early stages and its underlying cause corrected, late-stage cirrhosis is irreversible, and the only treatment option is a liver transplant. Patients with cirrhosis of the liver are thus subject to a wide range of complications and have decreased life expectancy.

Cirrhosis is a slowly progressing, indolent disease in which healthy tissue in the liver is injured and replaced with scar tissue and ultimately progresses to hepatic fibrosis. This fibrosis interrupts the normal flow of blood through the liver, resulting in impaired function. As a result, vital functions such as the synthesizing and storage of nutrients, the secretion of clotting factors and plasma proteins, and the clearing of toxins in the blood cannot occur. In addition, the impaired flow of blood through the liver results in a backup of blood into the hepatic portal circulation. This backup results in an increase of pressure into the portal, gastric, esophageal and mesenteric veins, a condition termed portal hypertension.4

Portacaval anastomoses are connections between veins of the portal system and the systemic circulation. The most important anastomoses are in the esophagus and rectum, but there are others as well. When portal hypertension occurs, blood flow from the gastrointestinal tract is directed away from the liver and directly

© 2015 EMSWorld.com 2 EMSWORLD.com into systemic circulation, a condition termed portosystemic shunting. This can result in dilation of these anastomotic vessels Table 2: Signs and Symptoms of Cirrhosis and the creation of internal hemorrhoids, as well as gastric and Weakness, fatigue, weight loss; esophageal varices. Jaundice, pruritis;

Early cirrhosis is a disease that can progress undetected, causing Pale, greasy, floating feces; little to no pain until decompensation occurs. Decompensated Upper gastrointestinal bleeding; cirrhosis and liver failure are characterized by the occurrence Dark urine; of life-threatening complications such as ascites, spontaneous Ascites, abdominal distension; bacterial peritonitis, variceal hemorrhage and hepatic Caput medusae, palmar erythema, spider angiomas; encephalopathy. Altered mental status; Bruising, bleeding; SIGNS AND SYMPTOMS Gynecomastia; Table 2 lists the signs and symptoms associated with compensated Hypotension; and decompensated cirrhosis. It is worth understanding how Hepatomegaly, splenomegaly; and why these manifestations occur so you can put together the Asterixis; entire clinical picture when assessing a patient. Pain.

• Pain in the upper right quadrant of the abdomen can occur secondary to liver swelling and subsequent stretching of its protective capsule. This pain is sometimes referred to the right shoulder.

• Weakness, fatigue and weight loss can occur in the patient with chronic liver failure secondary to chronic malnutrition that results from insufficient nutrient, vitamin and mineral synthesis and absorption.

• Pale-colored feces occur when stercobilin, a bile pigment, is absent from the stool. Normally bilirubin is absorbed in the liver and eventually secreted into the small intestine as bile. In the small intestine, some bilirubin is broken down and converted to stercobilin, which is then excreted in the feces and is responsible for its brown color. In chronic liver failure, bilirubin is not absorbed by the liver, and so less bile is produced and secreted into the small intestine, leading to less creation of stercobilin and ultimately gray or white stool. In addition, the lack of bile secretion in to the small intestine leads to a decrease in fat absorption, producing feces that contains excess fat, a condition known as steatorrhea. Such feces may float, due to excess gas, and have an oily or greasy appearance.

• Dark urine occurs when bilirubin is present in the urine. If unabsorbed by the liver (as described above), bilirubin remains in the bloodstream and is excreted by the kidneys, turning the urine a dark amber, cola or even brown color.

• Jaundice, also known as icterus, is a yellowish discoloration of the skin, conjunctival membranes of the sclera and other mucus membranes. As bilirubin levels increase in the blood, it results in an increase of bilirubin in tissues such as the skin and mucus membranes. A serum bilirubin of greater than 2–3 mg/dL is usually required to produce jaundice. The conjunctiva of the eyes are one of the first tissues to become jaundiced as bilirubin levels rise. Patients may also develop pruritis, or itchy skin.

• Ascites occurs secondary to the third-spacing of fluid from the cardiovascular system into the abdominal cavity. In chronic liver failure, the liver does not produce adequate levels of albumin. Albumin is necessary to maintain the colloidal osmotic pressure of blood. This colloidal osmotic pressure keeps fluid in the vascular system. When albumin is not present in sufficient concentrations, the osmotic gradient between the bloodstream and surrounding tissues is changed, and fluid flows out of the cardiovascular system and into the surrounding tissues. Abdominal ascites is the most common manifestation of third-spacing and edema, though peripheral edema in the extremities and pulmonary edema can also occur.

• The liver plays an important role in the synthesis of clotting factors. When it’s diseased, these factors are present in insufficient amounts. As a result, patients will bruise easily, and severe bleeding can occur.

• Caput medusae are dilated periumbilical veins. They occur as a direct result of portal hypertension. Blood and pressure back up in the portal circulation into the periumbilical and abdominal wall veins, which become distended, prominent and easily visible.

• Fetor hepaticus is a condition characterized by a foul-smelling breath. It is observed in patients with liver failure and subsequent portal hypertension and portosystemic shunting. A sweet, pungent odor is created on the breath when thiols, normally filtered out of the blood in the liver, enter systemic circulation and are released from the lungs with exhalation.5

• In liver failure, increased estrogen in the blood (in males and females) results in dilation of a cutaneous arteriole and engorging of the surrounding veins, giving the appearance of a central red dot and surrounding “spider legs.” These angioma are most often found on the trunk, upper limbs and face.5

• As with spider angioma, palmar erythema, reddening of the palms, also occurs as a result of increased estrogen levels in the blood.

• Gynecomastia, an increase in breast tissue and gland size in males, is yet another result of increased estrogen levels in the blood.

• Patients will often experience a decrease in mean arterial pressure as cirrhosis progresses, and those who were previously hypertensive may become normotensive or hypotensive.6

• Hepatomegaly: When palpable, the cirrhotic liver will have a hard and nodular surface. In healthy patients the liver is difficult to palpate, as it is protected by the rib cage. An enlarged liver, as may be the case in a patient with cirrhosis, may extend well below the rib cage.

• Asterixis, also known as the flapping tremor, is the bilateral asynchronous flapping or jerking motions of the hands when bent up at the wrist (dorsiflexion). It is most often seen in hepatic encephalopathy.

SPECIFIC MEDICAL EMERGENCIES Variceal Hemorrhage A varix is an abnormally dilated vessel with a tortuous course. Varices typically occur in the venous system but may also occur in arteries or lymphatic vessels. Esophageal and gastric varices can occur in the esophageal

© 2015 EMSWorld.com 3 EMSWORLD.com and gastric veins secondary to the portal hypertension that results from cirrhosis. These varices do not cause any symptoms until they leak or rupture, resulting in potentially life-threatening hemorrhage.

Less severe bleeding or leaking will result in signs of upper gastrointestinal bleeding such as melana (dark, tarry stool) or bloody diarrhea, dizziness, hypotension, tachycardia and syncope. Severe cases of variceal hemorrhage may present with the vomiting of blood (hematemesis) and the rapid onset of hypovolemic shock and death.

Hepatic Encephalopathy Hepatic encephalopathy is a term used to describe a spectrum of neurologic abnormalities seen in patients with liver dysfunction, occurring in 10%–50% of persons with cirrhosis.7,8 Characteristics of hepatic encephalopathy include the normal signs and symptoms characteristic of cirrhosis in addition to derangements in mental status, level of consciousness and neuromuscular function. In the early stages patients may present with insomnia or hypersomnia, lethargy, mild disorientation, a shortened attention span, disorientation to time, euphoria or depression or irritability, and neurologic manifestations such as tremor, muscular incoordination or asterixis. In the mid stages, patients may experience somnolence or confusion, disorientation to place, decreased inhibitions, inappropriate behavior and anxiety. Slurred speech, ataxia, loss of reflexes and nystagmus are common neurologic findings. In late-stage hepatic encephalopathy, signs such as muscular rigidity, dilated pupils and stupor or coma are present.

Spontaneous Bacterial Peritonitis SBP is an acute infection of ascitic fluid in the abdomen without a readily identifiable and surgically treatable source. It typically occurs in patients with advanced cirrhosis.9 It is important that patients with SBP are identified early in course of infection, as there is a short window of opportunity for successful treatment. If unidentified, SBP can lead to shock, multisystem organ failure and death.9 As such, identification of these patients in the field and transport to an emergency department for evaluation and treatment is important.

Suspect SBP in patients with a history of advanced cirrhosis and ascites who develop signs and symptoms such as abdominal pain, fever and altered mental status. On physical exam there will usually be diffuse abdominal tenderness.

PATIENT MANAGEMENT There is no specific out-of-hospital treatment for cirrhosis, only for the potentially life-threatening complications described above. Treatment for the complications of cirrhosis revolves around supportive care and the maintenance of airway, breathing and circulation. EMS care also should take into account the reduced hepatic function the patient has and avoid medications metabolized by the liver without discussing dosing with medical control—a simple dose of acetaminophen to treat a fever may be life-threatening, and a normal dose of a short-acting drug like midazolam may still affect a patient’s mental status many hours later.

Airway and Breathing Patients with suspected SBP, variceal bleeding or hepatic encephalopathy should receive oxygen at a concentration and with a device sufficient to maintain a saturation of at least 94%. In patients whoare unstable and may decompensate, it is advisable to attempt to achieve an oxygen saturation of 100% in an effort to create and maintain an oxygen reserve in the blood; this will lengthen the time to hypoxia should the patient’s condition deteriorate. Patients with active hematemesis will require aggressive airway suctioning and possibly intubation.

Patients with hepatic encephalopathy and SBP may have an altered level of consciousness that requires airway control. Any patient with gurgling or snoring respirations should have their airway suctioned and a BLS airway adjunct inserted. If the airway cannot be kept open with BLS airway adjuncts, consider a more secure supraglottic airway (King airway, LMA, etc.) or endotracheal tube. If they’re used in your service following advanced airway placement, naso- or orogastric tubes should be carefully considered because of the potential for disrupting varices.

Circulation Patients presenting with hypotension should be placed supine to maintain adequate cerebral blood flow. Obtain large-bore peripheral IV access (14- or 16-gauge angiocath in the antecubital). Administer fluid volume utilizing an isotonic crystalloid solution such as normal saline to maintain a mean arterial pressure above 60 mmHg.

Patients with hypotension secondary to SBP are experiencing severe sepsis and should be managed, from a fluid volume replacement perspective, as any patient with severe sepsis. The optimal volume of fluid that should be administered in patients with SBP and hypotension is unknown. It is prudent to administer rapidly infused 250–500-mL boluses of an isotonic crystalloid solution. Evaluate peripheral tissue perfusion, mental status, blood pressure and the presence of pulmonary edema after each bolus to determine the effectiveness of treatment. It is conceivable that a patient in shock would receive 1–2 liters or more of fluid in the prehospital setting. Consider vasopressors such as norepinephrine in the treatment of SBP and shock refractory to fluids.

Patients with variceal hemorrhage are very similar to trauma patients when considering fluid volume resuscitation. As in any patient with hypovolemic shock secondary to an uncontrollable internal hemorrhage, fluid volume resuscitation should be conservative, or at least not overzealous, to avoid fluid volume overload and worsening hemorrhage. In patients with massive hemorrhaging from variceal bleeding, lost blood volume is ideally replaced with a blood transfusion and clotting factors as necessary.

Article references available at EMSWorld.com/12113585.