Albumin hepatic synthesis

Sodium retention and hypo albumin aemi a are constant features. The former appears consequent on disturbed blood volume distribution, withslanch-nic dilatation and reduced effective central arterial blood volume leads to sodium retention. Hypoalbu-minaemia associated with reduced hepatic albumin synthesis, and raised portal pressure associated with obstruction to flow, as well as active sodium retention all predispose to ascites. Hypoalbuminaemia is associated with reduced hepatic synthesis. 

In clinical practice, only a few laboratory tests are of value in tlie assessment of protein-energy status It is particularly important to recognize that serum protein concentrations are not helpful in sick patients with any form of inflammatory process (see Chapter 20). Although serum albumin is often measured and reported as an indicator of protein-energy status, factors such as increased transcapillary escape and reduced hepatic synthesis malce it of little value as a nutritional marker. Serum albumin is, however, a valuable prognostic marker and is frequently used as part of prognostic indices. Short half-life proteins, such as transthyretin (prealbumin) also may be of some limited value in patients with no inflammatory response. 

Nephrotic syndrome is characterized by proteinuria greater than 3.5 g/day per 1.73 m, hypoproteinemia, edema, and hyperlipidemia. A hypercoagulable state may also be present in some patients. The syndrome may be the result of primary diseases of the glomerulus, or be associated with systemic diseases such as diabetes mellitus, lupus, amyloidosis, and preeclampsia. Hypoproteinemia, especially hypoal-buminemia, results from increased urinary loss of albumin and an increased rate of catabolism of filtered albumin by proximal tubular cells. The compensatory increase in hepatic synthesis of albumin is insufficient to replenish the protein loss, probably because of malnutrition. 

The cholinesterases are generally accepted as being synthesized in the liver, and the assay of cholinesterase first became of interest to the clinician and to the clinical chemist as a test of liver function. Low serum cholinesterase activities are found in acute hepatitis, acute cirrhosis, and in liver metastases—that is, in those conditions where the hepatic synthesis of the protein is impaired. The synthesis of several other proteins is also reduced in such conditions, so that cholinesterase assay has been largely superseded as a test of liver function by measurements related to such proteins as albumin and prothrombin. Nevertheless, cholinesterase still has a place in the assessment of hepatic and other diseases, as discussed in Section 5.2. 

All of the information obtained on the amounts and patterns of urinary proteins should be interpreted, together with plasma measurements—particularly for evidence of glomerular nitration changes—and altered hepatic protein synthesis. For example, loss of large amounts of urinary albumin may result in hypoalbuminemia, or the hypoalbumineamia may reflect reduced hepatic synthesis with no evidence of marked changes of renal clearance of albumin. 

Hypoproteinemias are characterized by reductions in albumin and/or globulin fractions reductions of albumin may be due to reduced hepatic synthesis or increased losses via the kidney or intestinal mucosa and several other tissues. Severe hypoproteinemia can be associated with edema and ascites due to the major osmotic influence of albumin. Some compounds, such as colchicines and cycloheximide, can... 

It is important to distinguish between changes in zinc metabolism which occur as a secondary effect of disease, injury, infection and drug therapy and alterations caused by a primary nutritional zinc deficiency. There is confusion in the literature because a number of unrelated causes can temporarily lower the concentration of zinc in plasma, and this is reported uncritically as evidence of nutritional depletion. Since a high proportion of zinc in plasma is albumin bound, any circumstance which lowers plasma albumin wiil also lower plasma zinc. For example, the changes seen in severe liver disease are primarily caused by a failure of hepatic synthesis of plasma proteins such as albumin. This results in problems in the distribution of zinc and eventual tissue depletion. It is questionable whether zinc supplementation of diet is worthwhile without some restoration of hepatocyte function, by effective treatment of the underlying disease (Mills et al., 1983). 

Contraindications for the TACE are poor performance status (Karnofsky status <50%), nutritional impairment, neoplastic ascites, high serum bilirubin level (> 3 mg%), poor hepatic synthesis (serum albumin < 2.0 mg/dl) and renal failure (serum creatinine > 2 mg%). There should be an adequate amount of residual uninvolved liver tissue. A tumor burden of more than 50%-75% resulting in an inadequate liver function is regarded as a contraindication for performing TACE (Therasse et al. 1993 Gates et al. 1999). Likewise florid infections or myelosuppres-sion (white blood cell count < 2000/ml, elementary bodies < 100,000/pl) are classified as contraindications for TACE. 

Albumin (69 kDa) is the major protein of human plasma (3.4-4.7 g/dL) and makes up approximately 60% of the total plasma protein. About 40% of albumin is present in the plasma, and the other 60% is present in the extracellular space. The liver produces about 12 g of albumin per day, representing about 25% of total hepatic protein synthesis and half its secreted protein. Albumin is initially synthesized as a preproprotein. Its signal peptide is removed as it passes into the cisternae of the rough endoplasmic reticulum, and a hexapeptide at the resulting amino terminal is subsequently cleaved off farther along the secretory pathway. The synthesis of albumin is depressed in a variety of diseases, particularly those of the liver. The plasma of patients with liver disease often shows a decrease in the ratio of albumin to globulins (decreased albumin-globuhn ratio). The synthesis of albumin decreases rela-... 

Table 1.10. Some pharmaceutical substances originally isolated from animal sources. While some are still produced by direct extraction from the native source, others are now also produced by direct chemical synthesis (e.g. peptides and some steroids), or by recombinant DNA technology (most of the pol5 peptide products). Abbreviations hGH = human growth hormone FSH=follicle stimulating hormone hCG=human chorionic gonadotrophin HSA=human serum albumin HBsAg=hepatitis B surface antigen...

Both forms of PEM are associated with hy-percortisolemia.The level of cortisol in kwashiorkor is lower, however, than in marasmus, likely due to decreased adrenocortical function caused by low protein intake (and not adrenal failure). If a sufficiently high level of cortisol is not maintained, then adequate muscle protein is not mobilized to sustain hepatic protein synthesis. Indeed, hypoproteinemia, evident by the decreased serum albumin and transferrin levels, is more acute in kwashiorkor than marasmus. 

Albumin is synthesized primarily by the hepatic parenchymal cells except in early fetal life, when it is synthesized largely by the yolk sac. The synthetic reserve of the liver is enormous in nephrotic syndrome, it may be 300% or more of normal. The synthetic rate is controlled primarily by colloidal osmotic pressure (COP) and secondarily by protein intake. Synthesis is decreased by inflammatory cytokines, and release (but not synthesis) is decreased by hypokalemia. Catabolism occurs primarily by pinocytosis by aU tissue, with lysosomal catabolism of the protein and use of the resulting free amino acids for synthesis of cellular proteins. The rate of pinocytosis is proportional to the local tissue metaboHc rate. Small amounts (10% to 20% of the total catabolized) are also lost into the gastrointestinal tract... 

Hepatic Disease. The liver retains the ability to synthesize even increased amounts of albumin until parenchymal damage or loss is severe, with the loss of 50% to 95% of function. Thus other mechanisms are responsible for the decreased levels seen in most cases of hepatocellular disease." These include, among others, increased immunoglobulin levels, third space loss (extravasation into the extravascular space), and direct inhibition of synthesis... 

One of the smallest and the most abundant plasma proteins, albumin plays a significant role in osmotic regulation and transport of free fatty acids. Albumin is synthesized in the liver at a rate of approximately 14 g/d, or 10% of the total protein synthesis of the body. Deviations from the normal concentration of albumin in plasma can indicate the state of hepatic function. Albumin is also present in interstitial fluid. 

In mice fed a tryptophan-deficient diet ad libitum for 1 week, Jones et al.31 reported on tissue serotonin synthesis rates, systemic tryptophan metabolism, and its response to steroid or cycloheximide treatment. In the experimental mice, brain serotonin synthesis was decreased while duodenal serotonin synthesis was increased following a tryptophan load. Liver total protein was depressed in experimental mice but increased following a tryptophan load. Blood tryptophan (total and free) and albumin were decreased in experimental mice, but ratios of albumin-bound tryptophan were increased. Enzyme kinetic studies indicated that, in experimental mice, brain tryptophan-5-hydroxylase had a reduced Vmax but the enzyme response to tryptophan or hydrocortisone injection was increased. However, hepatic tryptophan-2,3-dioxygenase response to tryptophan or hydrocortisone injection was blunted in experimental mice. 

After establishing that L-tryptophan alone stimulated overall hepatic protein synthesis, it became important to determine which proteins were involved. Increased synthesis of albumin due to L-tryptophan was reported by Rothschild et al.65 and by Jorgensen and Majumdar.47/18 The latter investigators also reported that tryptophan increased the synthesis of transferrin, fibrinogen, and ferritin. Thus, extracellular as well as intracellular proteins that are synthesized by the liver were affected by L-tryptophan. Furthermore, it was demonstrated that after L-tryptophan administration, both free and membrane-bound polyribosomes of the liver showed a shift toward heavier aggregation, more marked for free polyribosomes than for membrane-bound polyribosomes.62 Also, in vitro protein synthesis revealed a greater increase with free polyribosomes than with membrane-bound polyribosomes of the livers of tryptophan-treated animals in comparison with similar fractions of livers of control animals. 

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