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If the glycogenstores are not used, excess glucose (not released intothe blood) will eventually be converted to triglycerides(TG) and transported to adipose tissue for storage (see“Lipids”).Gluconeogenesis: The liver (and to a lesser extent, thekidney) has the ability to make glucose from substratessuch as glycerol, pyruvate, and the amino acids glutamine and alanine. This provides an alternate energyHepatobiliary Function■source and occurs primarily during fasting andstarvation.Formation of chemical compounds: Excess glucose canalso be converted into other chemical compounds(pyruvic acid, lactic acid, acetyl CoA) that can be usedin metabolic pathways such as the citric acid cycle.287■■immunoglobulins, which contribute to immunefunctions■ fibrinogen, which is necessary for blood clottingInterconversion of amino acids: Needed amino acids aresynthesized from other available amino acids.LipidsPRODUCTION AND SECRETION OF BILEMost lipids are packaged into chylomicrons in the enterocytes(see Chapter 25).
The chylomicrons enter the lymph lactealsin the small intestine, entering the systemic blood in the largevessels in the thoracic cavity. Thus the first entry of absorbedlipid into the liver is from the systemic, not portal, circulation.Liver lipid metabolism includes the following:Bile is critical for transport of lipids through the unstirredwater layer to the enterocytes. The unstirred water layer is thearea in the gut lumen that is closest to the villous lining. Thereis little flow near the cells, and the water and mucus create abarrier that impedes access of the hydrophobic lipids to theenterocytes (carbohydrates and proteins have no troublepassing through this area).
This challenge is met by bile, whichis amphipathic (has both hydrophilic and hydrophobicregions) and thus is able to move lipids across the unstirredwater. Bile and lipids form micelles, which act like taxis toshuttle the lipids through the unstirred water layer to theenterocytes (discussed further in Chapter 25). Bile solids arecomposed of bile salts (50%), phospholipids (40%), andsmaller amounts of cholesterol (∼4%), bilirubin (∼2%), andwater and electrolytes. Secreted bile is composed of the bilesolids, water, and electrolytes.■■■■b-Oxidation of fatty acids: Although many tissues useβ-oxidation as a source of energy when needed, the rateis very high in the liver.Formation of most lipoproteins: Very low densitylipoprotein (VLDL), low density lipoprotein (LDL), andhigh density lipoprotein (HDL) are formed in the liver.VLDL and LDL transport TG and cholesterol to tissues.LDL is implicated in development of cardiovasculardisease because it is incorporated into atheroscleroticplaques.
HDL transports lipids from tissues to the liverand is considered beneficial.Synthesis of cholesterol and phospholipids: These substrates are necessary for making membranes, and cholesterol is also the precursor for steroid hormones andbile. Because of these important functions, the liverensures a supply of these substrates by forming themfrom other lipids. A liver enzyme, hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase, is the rate-limitingstep in cholesterol synthesis, and pharmacologic intervention by statins (cholesterol-lowering drugs) inhibitsthis enzyme.Conversion of unused glycogen to TGs: If liver glycogenis not used, it is converted to TGs, which are transportedto adipose tissues in VLDLs.In the liver, primary bile acids (cholic, chenodeoxycholicacids) are synthesized in the hepatocytes from sterol rings(from cholesterol).
There are several important aspects of bilesynthesis and secretion:■■ProteinsProtein metabolism in the liver is essential for survival; theliver processes dietary amino acids and participates in theprocessing of nitrogen wastes for excretion. The major functions of the liver in this regard are:■■■Deamination of amino acids: This prevents toxinbuildup, because aminotransferases remove the aminogroup from the amino acids, creating ammonia (NH3).Production of urea: The NH3 combines with CO2 toform urea, thereby buffering NH3 and allowing urinaryexcretion.Synthesis of plasma proteins: About 90% of plasma proteins are made in the liver.
This includes:■ albumin, which contributes to oncotic pressure■■In the liver, one side of the primary bile acid is conjugated with an amino acid (either taurine or glycine),forming a bile salt. This conjugation increases the watersolubility of bile in the lower pH found in the duodenum. The primary bile salts are secreted into the bilecanaliculi, or ductules, and into the common bile duct(see Fig.
24.2).Bile salts are osmotic, and their secretion will drawwater, and then solvents (sodium chloride, HCO3−)from the cells—this is called solvent drag and contributes to the buffering capacity of the bile when it entersthe duodenum.After micelles are formed and the lipids are dropped offat the enterocytes, the majority of the bile remains in thelumen of the small intestine until the terminal ileum,where Na+-dependent transporters recycle the primarybile into the portal vein back to the liver. This bile recycling will occur three to five times for each meal andallows for efficient absorption of the lipids without synthesis of large amounts of bile, because it is reused.However, with each cycle, about 10% of the bile is notabsorbed but is lost in the feces.
This is the majorpathway by which cholesterol is removed from thesystem; other substances including bilirubin are alsoexcreted. The synthesis of bile acids is under feedbackcontrol by bile salts entering the liver from the portal288Gastrointestinal PhysiologyCLINICAL CORRELATEPortal Hypertension and Esophageal Varices in ObstructiveLiver DiseaseIncreased blood pressure in the portal vein can result from suprahepatic pathology (e.g., increase in systemic venous pressures, aswith congestive heart failure) or hepatic pathology (e.g., obstructive liver disease).
Obstructive liver disease is most commonly aresult of cirrhosis or fibrous scarring of the liver, which severelydecreases the flow of blood through the organ. In the UnitedStates, alcoholism and hepatitis C infection are the most commoncauses of cirrhosis. Interestingly, alcoholism causes cirrhosis of theliver or pancreatitis in individual patients, but not both diseases.sion results in increased backpressure in vessels coming fromthe stomach and esophagus, causing enlargement and thinning ofthese vessel walls, forming varices. The thin walls, high pressure,and increased radius in the varices make them susceptible torupture, and because of the superficial nature of the vessels servingthe esophagus, rupture may cause severe bleeding into the esophageal lumen, requiring immediate medical attention.
Treatment ofvarices is by either sclerotherapy (injecting a solution to block thevessels), or rubber-band ligation of the varices, where a band iswound around the varices, cutting off blood flow. The atrophiedarea sloughs off, leaving a healed scar. Portal hypertension can alsoresult in ascites and hemorrhoids, again caused by the backup inpressure in the portal venous system.In the cirrhotic liver, the obstruction of blood flow through theliver increases pressure in the portal system. This portal hyperten-Suprahepatic causesTricuspid incompetenceConstrictive pericarditisThrombosis of hepaticveins (Chiari syndrome)No or few esophageal varicesSpleen moderately enlargedIntrahepatic causesLiver enlargedEsophageal varicesSpleen markedly enlargedLiver cirrhosis (or schistosomiasis)Infrahepatic causesEsophageal varicesSpleen decidedly enlargedPortal vein thrombosisEsophageal VaricesHepatobiliary Function■■circulation.
Reduced bile salts will increase cholesterol7a-hydroxylase, which controls bile synthesis.In the intestines, some of the primary bile acids undergodehydroxylation by bacteria, forming secondary bileacids (deoxycholic, lithocholic acids), which are less efficient at crossing the unstirred water layer, and hence areless readily absorbed.When the stomach is emptied and chyme is no longerpresent in the duodenum, the sphincter of Oddi willclose. As the bile is recycled through the portal systemback through the liver, it will stop at the sphincter ofOddi, and back up into the relaxed gallbladder, where itwill be stored until the next meal.BASIC ENDOCRINE FUNCTIONSThe liver produces or modifies several endocrine and paracrine substances, including the following:■Insulin-like growth factor-I (IGF-I), which is releasedby the liver into the circulation in response to growth■■■■289hormone.
IGF-I mediates many of the somatic effects ofgrowth hormone.Angiotensinogen, which is the precursor to angiotensinI and II (angiotensin II plays an important role in bloodpressure regulation).Thrombopoietin (TPO), which stimulates stem cells inbone marrow to differentiate to megakaryocytes, whichgive rise to platelets.
Platelets are participate in bloodclotting.Hepatocyte growth factor (HGF), which acts locally tostimulate regeneration of liver cells and is especiallyimportant when the organ is damaged.Vitamin D metabolism: The liver hydroxylates cholecalciferol (from diet or synthesized in skin) to form 25hydroxycholecalciferol. This is still inactive and mustbe further hydroxylated in the kidney to become theactive form of vitamin D, 1,25-dihydroxycholecaliferol.Vitamin D is a key regulator of intestinal calciumabsorption.This page intentionally left blank291CHAPTER25Digestion and AbsorptionANATOMY AND NUTRIENT ABSORPTIONAbsorption of nutrients in the small intestine depends on anintact villous lining, which is designed to facilitate efficientnutrient uptake into the body.
The lumen of the small intestine is composed of circular folds, villi, and microvilli(Fig. 25.1). This increases the surface area of the small intestine to approximately 250 square meters and dramaticallyincreases the efficiency of the system so that most of the nutrient absorption will occur by mid- to late-jejunum.
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