A Comprehensive Perspective on Liver Physiological Function and the Pathological Evolution of Liver Cirrhosis: From Metabolic Detoxification Mechanisms to Analysis of Compensatory Factors

Chapter Seven: Sub-health and Liver and Kidney Diseases. Sub-health is a broad concept encompassing several interconnected stages. The stage closely adjacent to health can be termed "mild psychosomatic imbalance," often characterized by fatigue, insomnia, poor appetite, and emotional instability. These imbalances are easily recovered from, resulting in a state indistinguishable from that of a healthy person. This stage affects 25%–28% of the population. If this imbalance persists, it can progress to a "latent clinical" state, at which point it exhibits a high risk of developing certain diseases, harboring a high probability of progressing to a specific condition. Liver and kidney diseases also evolve from this "latent clinical" state.

Section 1 Liver Diseases I. Physiological Functions of the Liver The liver performs important and complex physiological functions, among which the following are clearly defined and clinically significant: (I) Bile Secretion Approximately 600-1000 ml of bile is continuously secreted daily, flowing into the duodenum through the bile ducts to aid digestion and the absorption of fat-soluble vitamins A, D, E, and K. (II) Metabolic Functions Nutrients absorbed from the intestines after food digestion enter the liver via the portal vein system. The liver converts carbohydrates, proteins, and fats into glycogen, which is stored within the liver. When blood glucose levels decrease, glycogen is broken down into glucose and released into the bloodstream. In terms of hormone metabolism, the liver has an inactivating effect on estrogen and antidiuretic hormone secreted by the posterior pituitary gland; most of the intermediate metabolism of adrenal cortex hormones and aldosterone occurs in the liver. In cirrhosis, the inactivating effect is reduced. Increased estrogen levels in the body cause spider angiomas, palmar erythema, and gynecomastia in men; increased antidiuretic hormone and aldosterone promote water and sodium retention, leading to edema and ascites. (III) Coagulation Function: The liver is the site of the formation or production of many coagulation substances. In addition to the synthesis of fibrinogen and prothrombin, it can also produce a variety of coagulation factors. (IV) Detoxification Function: Toxins produced during metabolism or foreign toxins are rendered non-toxic in the liver mainly through decomposition, oxidation, and conjugation. Glucuronic acid and glycine are the main components involved in conjugation, binding with toxins to render them non-toxic or eliminating them from the body. (V) Phagocytosis or Immune Function: The liver removes bacteria, pigments, or other debris from the blood through phagocytosis by Kupffer cells of the reticuloendothelial system.

II. Common Symptoms of Liver Disease The most prominent symptoms are fatigue and loss of appetite. Common symptoms include lower rib pain or discomfort, nausea, aversion to oily foods, loss of appetite, postprandial fullness, jaundice, dry mouth, constipation or loose stools, dark urine, low-grade fever, dizziness, tinnitus, and a sallow complexion. In cases of cirrhosis, in addition to the clinical manifestations of hepatitis, there may be ascites, prominent abdominal wall blood vessels, generalized edema, oliguria, palmar erythema, spider angiomas, and in severe cases, massive bleeding.

III. Liver Cirrhosis Liver cirrhosis is a common chronic liver disease. It is caused by long-term or repeated damage to hepatocytes from one or more pathogenic factors, leading to hepatocyte degeneration, necrosis, regeneration, and diffuse connective tissue proliferation, resulting in the destruction of liver lobule structure, the formation of pseudolobules, and hardening of the liver. Therefore, liver cirrhosis is a late-stage manifestation of various diffuse liver diseases. Common causes include viral hepatitis, schistosomiasis, liver fluke disease, alcoholism, malnutrition, and hepatotoxic drugs and chemicals. Clinically, it presents as a chronic process with varying degrees of liver function impairment and portal hypertension. Clinically, it is divided into two stages: compensated and decompensated. The former has mild, nonspecific symptoms, with normal or mildly abnormal liver function. The latter stage manifests as portal hypertension, liver function impairment, and ascites. Upper gastrointestinal bleeding, hepatic encephalopathy, secondary infections, and hepatorenal syndrome are common complications; some patients develop liver cancer. Once complications occur, the mortality rate is very high. Currently, treatment for cirrhosis can only aim to restore and maintain liver function, bring active lesions to a standstill, improve symptoms in the decompensated stage, and strive to restore the liver towards the compensated stage. It also aims to prevent and treat certain complications, thereby prolonging the patient's lifespan and maintaining a certain level of work and daily living ability. Cirrhosis is a common chronic liver disease caused by long-term or repeated exposure to one or more etiologies, resulting in diffuse liver damage. Clinically, in the early stages, due to strong liver function compensation, there may be no obvious symptoms. In later stages, multiple systems are affected, with liver function impairment and portal hypertension as the main manifestations, and serious complications such as gastrointestinal bleeding, hepatic encephalopathy, secondary infections, and cancer often occur.

IV. How does cirrhosis develop? Cirrhosis refers to liver fibrosis and nodular regeneration of residual hepatocytes caused by inflammation and necrosis of liver tissue from various causes. Liver fibrosis scar formation and nodular regeneration of hepatocytes are the liver's response to various long-term inflammatory, toxic, metabolic, and congestive damage. The presence of these factors promotes the formation of fibrous tissue in strip or ring-like patterns, with hepatocytes regenerating into nodules, pathologically termed pseudolobules. For example, alcoholic cirrhosis caused by long-term excessive alcohol consumption is a typical micronodular type of cirrhosis; cirrhosis caused by chronic viral hepatitis, resulting from repeated inflammation and necrosis of liver tissue, is often a macronodular type of cirrhosis. Liver fibrosis leads to liver structural destruction, loss of hepatic lobule morphology, and tortuosity of intrahepatic blood vessels, thereby increasing portal vein pressure, causing intrahepatic venous blood to shun arteries or form collateral vessels. This results in insufficient blood supply to hepatocytes, coupled with direct exposure to toxic, inflammatory, or metabolic substances, leading to functional dysfunction. Therefore, the clinical manifestations of cirrhosis are a series of liver function impairments and portal hypertension.

V. Etiology of Liver Cirrhosis There are many causes of liver cirrhosis, with viral hepatitis being the most common in China. Abroad, especially in North America and Western Europe, alcoholic cirrhosis is the most prevalent. (I) Viral Hepatitis Acute or subacute hepatitis with extensive hepatocyte necrosis and fibrosis can directly develop into cirrhosis, but the more important progression is through a stage of chronic hepatitis. (II) Chronic Alcohol Poisoning In Europe and America, alcoholic cirrhosis accounts for approximately 50%–90% of all cirrhosis cases, while it is rare in my country. Its pathogenesis mainly involves the direct damage to the liver caused by acetaldehyde, an intermediate metabolite of alcohol. (III) Hereditary and Metabolic Diseases Cirrhosis that gradually develops from hereditary and metabolic liver diseases is called metabolic cirrhosis. These diseases mainly include hemochromatosis, Wilson's disease, galactosemia, and glycogen storage disease. (IV) Liver congestion: Chronic congestive heart failure, chronic constrictive pericarditis, and hepatic vein obstruction syndrome caused by various etiologies can all lead to long-term liver congestion and hypoxia, resulting in liver damage. (V) Chemical toxins or drugs: Long-term use of certain drugs such as bisacodyl tincture, methyldopa, tetracycline, etc., or long-term repeated exposure to certain chemical toxins such as phosphorus, arsenic, carbon tetrachloride, etc., can all cause toxic hepatitis, eventually evolving into cirrhosis. (VI) Malnutrition: The relationship between malnutrition and cirrhosis is not yet clear. There are many causes of cirrhosis, and their pathological changes and clinical manifestations also vary. The same cause can develop into different pathological types of cirrhosis; and the same pathological type of cirrhosis can be evolved from multiple causes. Therefore, there is still no unified classification in theory and clinical practice based on etiology combined with its pathological morphology.