on 25-Nov-2021 (Thu)

Cirrhosis is a condition that is defined histopathologically and has a variety of clinical manifestations and complications, some of which can be life-threatening.

the pathologic features consist of the development of fibrosis to the point that there is architectural distortion with the formation of regenerative nodules. This results in a decrease in hepatocellular mass, and thus function, and an alteration of blood flow. The induction of fibrosis occurs with activation of hepatic stellate cells, resulting in the formation of increased amounts of col- lagen and other components of the extracellular matrix.

Laboratory tests may be completely normal in patients with early compensated alcoholic cirrhosis. Alternatively, in advanced liver disease, many abnormalities usually are present. Patients may be anemic either from chronic GI blood loss, nutritional deficiencies, or hypersplenism related to portal hypertension, or as a direct suppres- sive effect of alcohol on the bone marrow. A unique form of hemolytic anemia (with spur cells and acanthocytes) called Zieve’s syndrome can occur in patients with severe alcoholic hepatitis. Platelet counts are often reduced early in the disease, reflective of portal hypertension with hypersplenism. Serum total bilirubin can be normal or elevated with advanced disease. Direct bilirubin is frequently mildly elevated in patients with a normal total bilirubin, but the abnormality typically progresses as the disease worsens. Prothrombin times are often pro- longed and usually do not respond to administration of parenteral vitamin K. Serum sodium levels are usually normal unless patients have ascites and then can be depressed, largely due to ingestion of excess free water. Serum alanine and aspartate aminotransferases (ALT, AST) are typically elevated, particularly in patients who con- tinue to drink, with AST levels being higher than ALT levels, usually by a 2:1 ratio.

Patients who have any of the above-mentioned clinical features, physical examination findings, or laboratory studies should be considered to have alcoholic liver disease. The diagnosis, however, requires accurate knowledge that the patient is continuing to use and abuse alcohol. Furthermore, other forms of chronic liver disease (e.g., chronic viral hepatitis or metabolic or autoimmune liver diseases) must be considered or ruled out, or if present, an estimate of relative causal- ity along with the alcohol use should be determined. Liver biopsy can be helpful to confirm a diagnosis, but generally when patients present with alcoholic hepatitis and are still drinking, liver biopsy is withheld until abstinence has been maintained for at least 6 months to determine residual, nonreversible disease. In patients who have had complications of cirrhosis and who continue to drink, there is a <0% 5-year survival. In contrast, in patients who are able to remain abstinent, the prognosis is significantly improved. In patients with advanced liver disease, the prognosis remains poor; however, in individuals who are able to remain absti- nent, liver transplantation is a viable option.

Treatment is restricted to patients with a discriminant function (DF) value of >32. The DF is calculated as the serum total bilirubin plus the difference in the patient’s prothrombin time com- pared to control (in seconds) multiplied by 4.6. In patients for whom this value is >32, there is improved survival at 28 days with the use of glucocorticoids.

Other therapies that have been used include oral pentoxifylline, which decreases the production of tumor necrosis factor α (TNF-α) and other proinflammatory cytokines. In contrast to glucocorticoids, with which complications can occur, pentoxifylline is relatively easy to administer and has few, if any, side effects.

Abstinence is the cornerstone of therapy for patients with alcoholic liver disease. In addition, patients require good nutrition and long- term medical supervision to manage underlying complications that may develop. Complications such as the development of ascites and edema, variceal hemorrhage, or portosystemic encephalopathy all require specific management and treatment. Glucocorticoids are occasionally used in patients with severe alcoholic hepatitis in the absence of infection

the cornerstone to treatment is cessation of alcohol use. Recent experience with medications that reduce crav- ing for alcohol, such as acamprosate calcium, has been favorable. Patients may take other necessary medications even in the presence of cirrhosis. Acetaminophen use is often discouraged in patients with liver disease; however, if no more than 2 g of acetaminophen per day are consumed, there generally are no problems.

Hipoksik hücrede görülen ilk morfolojik bulgu? Hücre şişmesi (Na-K ATPaz pompası çalışamıyor, Na hücre içinde kalıyor, Su da çekiyor) 2.Bulgu ise Yağlanma’dır.

The kidney is both a target and a cause of hypertension. Primary renal disease is the most common etiology of secondary hypertension. Mech- anisms of kidney-related hypertension include a diminished capacity to excrete sodium, excessive renin secretion in relation to volume sta- tus, and sympathetic nervous system overactivity. Conversely, hyper- tension is a risk factor for renal injury and ESRD. The increased risk associated with high blood pressure is graded, continuous, and present throughout the distribution of blood pressure above optimal pressure. Renal risk appears to be more closely related to systolic than to diastolic blood pressure,

Atherosclerotic, hypertension-related vascular lesions in the kidney primarily affect preglomerular arterioles, resulting in ischemic changes in the glomeruli and postglomerular structures. Glomerular injury also may be a consequence of direct damage to the glomerular capillaries due to glomerular hyperperfusion. Studies of hypertension-related renal damage, primarily in experimental animals, suggest that loss of autoregulation of renal blood flow at the afferent arteriole results in transmission of elevated pressures to an unprotected glomerulus with ensuing hyperfiltration, hypertrophy, and eventual focal segmental glomerular sclerosis. With progressive renal injury there is a loss of autoregulation of renal blood flow and glomerular filtration rate, result- ing in a lower blood pressure threshold for renal damage and a steeper slope between blood pressure and renal damage. The result may be a vicious cycle of renal damage and nephron loss leading to more severe hypertension, glomerular hyperfiltration, and further renal damage. Glomerular pathology progresses to glomerulosclerosis, and eventually the renal tubules may also become ischemic and gradually atrophic. The renal lesion associated with malignant hypertension consists of fibrinoid necrosis of the afferent arterioles, sometimes extending into the glomerulus, and may result in focal necrosis of the glomerular tuft.

Clinically, macroalbuminuria (a random urine albumin/creatinine ratio >300 mg/g) or microalbuminuria (a random urine albumin/ creatinine ratio 30–300 mg/g) are early markers of renal injury. These are also risk factors for renal disease progression and cardiovascular disease