Cirrhosis pathophysiology

FIGURE 19-1. The portal venous system. (From Timm EJ, Stragand JJ. Portal hypertension and cirrhosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 694, with permission.)... 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

Cirrhosis results in elevation of portal blood pressure because of fibrotic changes within the hepatic sinusoids, changes in the levels of vasodilatory and vasoconstrictor mediators, and an increase in blood flow to the splanchnic vasculature. The pathophysiologic abnormalities that cause it result in the commonly encountered problems of ascites, portal hypertension and esophageal varices, HE, and coagulation disorders. 

Endocannahinoids play important roles in a variety of pathophysiological conditions including hemorrhagic, endotoxic, and cardiogenic shock, and in the hemodynamic sequelae of advanced liver cirrhosis. Furthermore, pharmacological manipulation of the endocannabinoid system may offer novel therapeutic approaches in hypertension and ischemic heart disease. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

This chapter elucidates the pathophysiology of cirrhosis and the resultant effects on human anatomy and physiology. Treatment strategies for managing the most commonly encountered clinical complications of cirrhosis are discussed. 

Hepatorenal syndrome, functional renal failure in the setting of cirrhosis in the absence of intrinsic renal disease, occurs in patients with cirrhosis as a result of intense vasoconstriction within the renal cortical vasculature. It is common and develops in approximately 40% of patients with cirrhosis and ascites within 5 years. The resultant reduction in blood supply to the kidneys causes avid sodium retention and oliguria. The vasoconstriction that occurs in the kidneys is in stark contrast to the state of systemic vasodilation that is characteristic of chronic liver failure. The pathophysiologic mechanism responsible for these effects is unknown, but is linked to the systemic vasodilation, hypovolemia, and hyperkinetic circulation seen in chronic liver failure. ... 

HAV is primarily responsible for acute hepatitis. It is most often linked to sporadic events of contaminated food in the United States and to international travel, and is usually a self-limited disease. HBV and HCV are primarily responsible for the development of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Immunomodulatory therapy and direct antiviral agents have been developed for both HBV and HCV. These therapeutic modalities require long courses of therapy and are associated with limited success. This chapter will focus on the pathophysiology, clinical course, and management of these three primary causes of viral hepatitis, namely HAV, HBV, and HCV. 

This technique may provide many new insights into the physiology of carbohydrate metabolism and also into pathophysiologic changes in patients with diabetes, liver cirrhosis or hepatitis. 

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