Today, I review, link to, and excerpt from “Hepatic Cirrhosis” From StatPearls. Bashar Sharma; Savio John. Last Update: October 31, 2022.
All that follows is from the above resource.
Introduction
Cirrhosis is characterized by fibrosis and nodule formation of the liver, secondary to a chronic injury, which leads to alteration of the normal lobular organization of the liver. Various insults can injure the liver, including viral infections, toxins, hereditary conditions, or autoimmune processes. The liver initially forms scar tissue (fibrosis) with each injury without losing its function. After a long-standing injury, most of the liver tissue gets fibrosed, leading to loss of function and the development of cirrhosis. See image. Cirrhosis, Liver.
Etiology
Chronic liver diseases usually progress to cirrhosis. In the developed world, the most common causes of cirrhosis are hepatitis C virus (HCV), alcoholic liver disease, and nonalcoholic steatohepatitis (NASH). In contrast, hepatitis B virus (HBV) and HCV are the most common causes in the developing world.[1] Other causes of cirrhosis include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, Budd-Chiari syndrome, drug-induced liver cirrhosis, and chronic right-sided heart failure. Cryptogenic cirrhosis is defined as cirrhosis of unclear etiology.
Epidemiology
The worldwide prevalence of cirrhosis is unknown; however, it has been estimated to be between 0.15% and 0.27% in the United States.[2][3]
Pathophysiology
Multiple cells play a role in liver cirrhosis, including hepatocytes and sinusoidal lining cells such as hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs), and Kupffer cells (KCs).
The major cause of morbidity and mortality in cirrhotic patients is the development of portal hypertension and hyperdynamic circulation. Portal hypertension develops secondary to fibrosis and vasoregulatory changes intrahepatically and systematically, leading to collateral circulation formation and hyperdynamic circulation.
Histopathology
Cirrhosis is classified based on morphology or etiology.
History and Physical
Patients with cirrhosis can be asymptomatic or symptomatic, depending on whether their cirrhosis is clinically compensated or decompensated. In compensated cirrhosis, patients are usually asymptomatic, and their disease is detected incidentally by labs, physical exams, or imaging. One of the common findings is mild to moderate elevation in aminotransferases or gamma-glutamyl transpeptidase with possible enlarged liver or spleen on the exam. On the other hand, patients with decompensated cirrhosis usually present with a wide range of signs and symptoms arising from a combination of liver dysfunction and portal hypertension. The diagnosis of ascites, jaundice, hepatic encephalopathy, variceal bleeding, or hepatocellular carcinoma in a patient with cirrhosis signifies the transition from a compensated to a decompensated phase of cirrhosis. Other cirrhosis complications include spontaneous bacterial peritonitis and hepatorenal syndrome, which occur in patients who have ascites.
Multiple Organs Affected
Gastrointestinal
Portal hypertension can cause ascites, hepatosplenomegaly, and prominence of the periumbilical abdominal veins, resulting in caput medusa. Esophageal varices are another complication of cirrhosis secondary to increased blood flow in the collateral circulation, with a mortality rate of at least 20% at 6 weeks after a bleeding episode.[10] Patients with alcoholic cirrhosis are at increased risk of small bowel bacterial overgrowth and chronic pancreatitis, and patients with chronic liver disease have a higher rate of gallstone formation.[11][12]
Hematologic
Anemia can occur due to folate deficiency, hemolytic anemia (spur cell anemia in severe alcoholic liver disease), and hypersplenism. There can be pancytopenia due to hypersplenism in portal hypertension, impaired coagulation, disseminated intravascular coagulation, and hemosiderosis in cirrhosis patients due to different causes.
Renal
Patients with cirrhosis are prone to develop hepatorenal syndrome secondary to systemic hypotension and renal vasoconstriction, causing the underfilling phenomenon. Splanchnic vasodilation in cirrhosis leads to decreased effective blood flow to the kidneys, activating the renin-angiotensin-aldosterone system, leading to sodium and water retention and renal vascular constriction.[13] However, this effect is not enough to overcome the systemic vasodilation caused by cirrhosis, leading to renal hypoperfusion and worsened by renal vasoconstriction with the endpoint of renal failure.[14]
Pulmonary
Manifestations of cirrhosis include hepatopulmonary syndrome, portopulmonary hypertension, hepatic hydrothorax, decreased oxygen saturation, ventilation-perfusion mismatch, reduced pulmonary diffusion capacity, and hyperventilation.
Skin
Spider nevi, central arterioles surrounded by multiple smaller vessels resembling a spider, are seen in cirrhosis patients secondary to hyperestrogenemia. Liver dysfunction leads to a sex hormone imbalance, causing an increased estrogen-to-free testosterone ratio and the formation of spider nevi.[15] Palmar erythema is another skin finding that is seen in cirrhosis and is also secondary to hyperestrogenemia. Jaundice is a yellowish discoloration of the skin and mucous membranes seen when the serum bilirubin is greater than 3 mg/dL and in decompensated cirrhosis.
Endocrine
Patients with alcoholic liver cirrhosis can develop hypogonadism and gynecomastia. The pathophysiology is multifactorial, mainly due to the hypersensitivity of estrogen and androgen receptors seen in cirrhotic patients. Hypothalamic pituitary dysfunction has also been implicated in the development of these conditions.[16] Hypogonadism can lead to decreased libido and impotence in males with loss of secondary sexual characteristics and feminization. Women can develop amenorrhea and irregular menstrual bleeding, as well as infertility.
Nail Changes
Clubbing, hypertrophic osteoarthropathy, and the Dupuytren contracture are seen. Other nail changes include azure lunules (Wilson disease), Terry nails, and Muehrcke nails.
Others
Fetor hepaticus (sweet, musty breath smell due to high levels of dimethyl sulfide and ketones in the blood) and asterixis (flapping tremor when the arms are extended and the hands are dorsiflexed) are both features of hepatic encephalopathy that can be seen in cirrhosis.[17] Cirrhosis can lead to hyperdynamic circulation, reduced lean muscle mass, muscle cramps, and umbilical herniation. Physical examination in patients with cirrhosis may reveal stigmata of chronic liver disease (spider telangiectasias, palmar erythema, Dupuytren contractures, gynecomastia, testicular atrophy), signs of portal hypertension (ascites, splenomegaly, caput medusae, Cruveilhier-Baumgarten murmur- epigastric venous hum), signs of hepatic encephalopathy (confusion, asterixis, and fetor hepaticus), and other features such as jaundice, bilateral parotid enlargement, and scant chest/axillary hair.
