Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2617_Библиотеки_им_академика_М_И_Перельмана

Urinary creatinine, commonly used to assess kidney func­tion, can give useful information about an individual’s mus­cle mass. Creatine is almost completely present in muscle (in the form of creatine phosphate) and is converted to creatinine at a relatively constant rate; therefore, excretion of creatinine in the urine may be a reliable indicator of muscle mass. The most widely used method for assessing urinary creatinine is to calculate the creatinine/height index, which is the ratio of the subject’s creatinuria to the ideal creatinuria of a reference subject of the same sex and height.

Chylomicrons are the largest lipoproteins synthesized at the intestinal level, with the primary role of transporting fats of exogenous origin, mainly triglycerides, absorbed at the enterocyte level, to the liver and peripheral tissues.

VLDLs are the very low-density lipoproteins synthesized in the liver. They represent the main plasma transport vehicle of endogenous triglycerides. The most represented apolipopro­tein is ApoB-100. Similar to chylomicrons, the size of VLDL can vary depending on the number of triglycerides trans­ported by the particle.

LDLs, the low-density lipoprotein, originate from IDL and have a high cholesterol content. Indeed, their main function is the transport of cholesterol in the plasma, both in free and esteried form.

Like VLDL, the major apolipoprotein in LDL is ApoB­100, which plays a key role as it mediates the interaction of the lipoprotein with its receptor expressed on the cell membrane.

atherogenic for several reasons. First, small and dense LDL has a lower afnity for the LDL receptor prolonging the lipo­protein’s stay in the bloodstream. In addition, they penetrate the artery wall more easily, where they bind more avidly to proteoglycans and become trapped. Finally, they are more susceptible to oxidation resulting in greater uptake by macrophages.

HDLs, the high-density lipoprotein, acts as a scavenger, mediating the cholesteroltransport, from peripheral tissues to the liver. Nascent HDLs, synthesized in the liver and intes­tine, known as pre-beta HDLs, pick up free cholesterol at the periphery through interaction with the ABCA1 (ATP- Binding Cassette transporter A1) enzyme, and esterify it through the membrane-associated LCAT (lecithin- cholesterol acyltrans­ferase)enzyme. The main inducer of the LCAT enzyme is ApoA-Iapolipoprotein, which represents the most abundant protein component of HDL.The continuous accumulation of esteried cholesterol in the lipoprotein core transforms the nascent HDL from discoidal particles to spherical parts, called HDL-3. Through the esteried cholesterol transfer pro­tein (CETP), HDL gives up esteried cholesterol, in exchange for triglycerides, to VLDL, IDL, and chylomicrons and is transformed into HDL-2. The latter, enriched in triglycerides, can be metabolized by hepatic and lipoprotein lipase and, thus, return to the nascent HDL stage, or be directly captured and degraded by the liver. The accelerated catabolism of tri­glyceride-rich HDL-2 explains the common nding of low HDL cholesterol levelsduring hypertriglyceridemia.

The physiological role of Lp(a) is not yet completely clear, but levels >30mg/dL are associated with an increased atherosclerotic risk. It is not known whether Lp(a) partici­pates directly or indirectly in the formation of atheroma. However, due to its homology with plasminogen, Apo(a) may inhibit brinolysis and promote thrombosis, thus inter­acting with the physiological mechanism of coagulation.

LPL is an enzyme synthesized in numerous tissues, includ­ing muscle and adipose tissue, secreted and anchored to heparan sulfate on the luminal surface of endothelial cells.

LPL catalyzes the hydrolysis of triglycerides, chylomicrons, and VLDL, releasing glycerol and fatty acids, which, once released, are picked up by cells. Triglyceride catabolism leads to the conversion of chylomicrons into chylomicron remnants and VLDL into IDL.LPL requires ApoC-II as a cofactor. In addition, ApoA-V also plays a key role in the activation of the enzyme. In contrast, ApoC-III and ApoA-II inhibit its activity. Insulin stimulates the expression of LPL, whereas the activity of the enzyme is reduced in patients with poorly controlled dia­betes, and this could impair the metabolism of triglyceride-rich lipoproteins, leading to hypertriglyceridemia.

The ABCA1 is expressed in most cells of the body, includ­ing hepatocytes, enterocytes, and macrophages, where it mediates the transport of cholesterol and phospholipids from cells to lipid-poor HDLs (pre-beta HDLs). Therefore, it plays a key role in the initial lipidation processes of nascent HDLs.

The ABCG1 is expressed in many cell types and mediates cholesterol efux from cells to mature HDLs.

The ABCG5/ABCG8 are expressed in the liver and intestine as heterodimers. In the intestine, these transporters mediate the ow of cholesterol from the enterocyte to the intestinal lumen, thereby reducing its absorption. In the liver, however, they promote the transport of cholesterol into the bile.

Hepatic lipase is located on the sinusoidal surface of hepato­cytes, where it mediates the hydrolysis of triglycerides and phospholipids of IDL and LDL, leading to the formation of smaller particles (IDLs are converted into LDLs, and large LDLs are converted into smaller particles).

It is a glycoprotein synthesized in the liver and released into plasma, where it mediates the transfer of cholesteryl esters

from HDL to VLDL, chylomicrons, and LDL, and the trans­fer of triglycerides from VLDL and chylomicrons to HDL. Inhibition of CETP activity leads to an increase in HDL cholesterol and a decrease in LDL cholesterol.

muscular tissue, LPL hydrolyses the triglycerides carried by the chylomicrons into glycerol and fatty acids. The latter are picked up by skeletal and cardiac muscle cells for energy production (beta-oxidation) and by adipocytes, where they are used as substrates for triglyceride synthesis and subse­quent accumulation as an energy reserve.

In the direct pathway, SR-B1 receptor, expressed on the surface of hepatocytes, mediates the HDL interaction and modication by selectively removing cholesterol from mature HDL, and thus transforming them into lipid-poor HDL remnants, ready for a new cycle.

From a nosographic point of view, there are different classi­cations of dyslipidemias, depending on the lipid alteration (hypercholesterolemia, hypertriglyceridemia, or mixed forms), the phenotypic aspect (Fredrickson classication), the biochemical-genetic defect (mono and polygenic altera­tions) or the pathogenicmechanism (primary and secondary dyslipidemias). Each of these classications has strengths and limitations.

The lipoprotein alteration is represented by increased chylo­microns associated with severe hypertriglyceridemia (>1000mg/dL) and low HDL levels. This phenotype is more frequently found in individuals with primary dyslipidemias due to a familial defect of the lipoprotein lipase enzyme, with theabsence or reduction of function, or to the absence of ApoC-II, an activator of lipase, or in individuals affected by other diseases, such as diabetes (insulin is an activator of lipase). Individuals with this phenotype frequently experi­ence pancreatitis due to elevated triglyceride levels.

encoding for ApoB, which make the protein poorly or not

recognizable by the LDL receptor, resulting in a reduction in

catabolized.