1133CHAPTER 94 Gastrointestinal Structure and Function absorption Brush border lipase enzymes are involved as well The milieu of the unstirred water layer is acidic (pH 5 to 6) owing to the activity o[.]
CHAPTER 94 Gastrointestinal Structure and Function absorption Brush border lipase enzymes are involved as well The milieu of the unstirred water layer is acidic (pH to 6) owing to the activity of the brush border membrane Na1/H1 exchanger The acid environment facilitates dissociation of fatty acids from micelles, resulting in a high concentration of fatty acids necessary for diffusion across the mucosal membrane Once inside the enterocyte, long-chain fatty acids and monoglycerides are resynthesized into triglycerides and packaged as chylomicrons Lipoproteins (e.g., apo-A, apo-B) and cholesterol are attached to the intestinal chylomicrons and confer important properties for the subsequent systemic uptake and metabolism of the chylomicrons The chylomicrons are exported into the intercellular space and transported through the intestinal lacteals to become part of the intestinal lymph On entering the bloodstream through the thoracic duct, the chylomicrons are associated with other apolipoproteins that allow them to be recognized by specific peripheral tissues.16 Dietary lipids containing short- and medium-chain (C6–C12) triglycerides (MCTs) are processed differently from those of longchain triglycerides As much as 30% of MCTs may be absorbed intact into enterocytes by passive diffusion and enter the portal venous blood directly MCTs are hydrolyzed by pancreatic and mammary lipases to fatty acids and monoglycerides and rapidly enter the enterocytes, where they emerge into the portal venous system without reesterification, as occurs with long-chain fatty acids Intestinal Lymphatics The intestinal lymph chyle is composed of chylomicrons and lipoproteins secreted by the intestinal epithelium in the postprandial state together with nonresorbed interstitial fluid Chyle follows the intestinal lymphatic channels along the mesentery and enters regional lymph nodes from which it flows cephalad through the thoracic duct and ultimately enters the central circulation In the fasting state, intestinal lymph production is relatively low It increases 20-fold during the active absorption of a typical meal The intestinal chyle is joined by lymphatic drainage from other tissues, including the liver and pancreas The protein content of chyle is 2.2 to 5.9 g/dL with a triglyceride content of 0.4 to 6.0 g/dL and 400 to 6800 lymphocytes/dL During digestion of a meal containing long-chain fats, chyle has a typical milky white appearance because of the presence of chylomicrons The rate of formation of chyle depends on the state of nutrient absorption, portal venous pressure, and the rate of lymphatic uptake Conditions that create portal hypertension (e.g., portal vein thrombosis, cirrhosis, congestive heart failure) or impair the flow of lymph back to the central circulation (e.g., increased central venous pressure, superior vena cava syndrome) predispose to the collection of chylous ascites in the abdomen Regulation of Electrolyte and Water Movement The movement of water is primarily coupled to the movement of solute in the form of electrolytes and nutrients It is largely passive, occurring through paracellular routes in the intestine coupled with solute movement Expression of transporters involved in intestinal water and electrolyte transport is regionally defined in the intestines Electrolytes are taken up by enterocytes at the apical membrane and extruded through the basolateral membrane into the paracellular space The relatively hypertonic paracellular fluid pulls water into this space, increasing the hydrostatic pressure locally Since the tight junction between enterocytes is more impermeable to fluid flux than the capillary membranes, fluid and 1133 electrolytes are preferentially driven in the direction of the vascular space Tight junctions are selective and dynamic in function and are regulated by a number of signaling pathways and cellular processes that can determine the size, selectivity, and flow of molecules across this barrier.17 The gut responds to both systemic and local stimuli to regulate motility, transport, and digestive functions Secretion and motility are mediated through typical agonist membrane receptor mechanisms, by local autocrine and paracrine action, or through remote endocrine and neurocrine actions.18 Regulation of peristalsis is crucial for keeping the chyme in contact with the epithelial surface long enough for efficient absorption of nutrients while permitting removal of unusable material and bacteria from the alimentary tract on a regular basis GI smooth muscle demonstrates phasic and tonic patterns of contraction Numerous factors affecting the frequency of contractions include changes in autonomic tone, stimulation of the gut by neurohormonal peptides or pharmacologic agents, and noxious stimuli associated with infectious or inflammatory processes Hypoxia and ischemia decrease motility, frequently leading to paralytic ileus Neural regulation of the GI tract integrates the processes of intestinal water and electrolyte transport, motility, and blood flow Augmentation of water and electrolyte absorption after a meal in the jejunum is neurally mediated The enteric nervous system, capable of functioning independently, is also influenced by the autonomic nervous system.19 Many other factors alter the functions of the gut The terminal ileum and colon are particularly important in this respect The presence of an ileostomy increases the risk of excessive sodium losses, dehydration, and electrolyte abnormalities Terminal ileal resection or other diseases of the terminal ileum such as Crohn disease or radiation enteritis may result in bile acid malabsorption In patients with bile acid malabsorption, bile acids reach the colon, which stimulates electrolyte and chloride secretion Patients with mild to moderate malabsorption present with watery diarrhea and may respond to a bile acid binder such as cholestyramine.20 Impairment of water and ion absorption in inflammatory bowel disease may occur owing to numerous mechanisms, including alteration of epithelial integrity, augmented secretion, and reduced absorption Intestinal inflammation is associated with defects in epithelial barrier function and has a major impact on fluid and electrolyte flux.21 Hyperosmolality of the ileal and colonic contents and the presence of unabsorbed bile acids in the colon lead to a diarrheal state This state is seen when unabsorbed nutrients enter the distal alimentary tract and are broken down by enteric bacteria, resulting in increased luminal osmotic activity and osmotic diarrhea Electrolyte Transport Several basic mechanisms exist for the transport of electrolytes by the epithelia, as summarized in eTable 94.1 The presence of glucose in the lumen of the small intestine stimulates increased sodium absorption through coupled transport Backflow of sodium into the lumen is a passive process since a major task for the GI tract is sodium conservation Systemic acidosis increases Na1 and chloride (Cl–) absorption in the ileum and colon, whereas alkalosis has the opposite effect As seen in other epithelial tissues, aldosterone increases ileal and colonic absorption of Na1 and can increase absorption of water in the colon three- to fourfold Spironolactone blocks this effect The previous enthusiastic use of glutamine in intestinal rehabilitation in the ICU has not been 1134 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition substantiated by recent studies.22 Glucocorticoids increase sodium and water absorption in the distal colon Opiate receptor stimulation increases active Na1 and Cl– absorption in the ileum, and opiate antagonists decrease basal absorption of water and electrolytes The primary antidiarrheal effect of opiates, however, is mediated through a slowing of intestinal transit time.23 In the colon, active absorption and secretion of K1 occurs in a manner consistent with K1/H1 exchange, is electroneutral, and is independent of Na1/Cl– exchange The process of Na1extrusion depends on Na1/K1-ATPase pumping function located at the basolateral membranes, which may be inhibited by oxidative stress during critical illness Extrusion of Cl– follows an electrochemical potential difference The intraluminal secretion of water and other electrolytes appears to follow active secretion of Cl– from the crypt cells of the jejunum, ileum, and colon, with the cystic fibrosis transmembrane conductance regulator (CFTR) mechanism playing an important role This is a common physiologic pattern in the liver, pancreas, and kidney Numerous substances—such as muscarinic receptor agonists, serotonin, and substance P—work through second messengers and signaling cascades to induce active Cl– secretion Vasoactive intestinal peptide (VIP) mediates increased secretion of electrolytes and water by increased cyclic adenosine monophosphate production that stimulates active Cl–secretion and inhibits Na1-Cl– absorption Certain arachidonic acid metabolites, such as prostaglandins (e.g., prostaglandin E1), increase active Cl– secretion with increased loss of electrolytes and fluid Many laxatives and antacids may affect fluid and electrolyte balance by stimulating active electrolyte and fluid secretion in the terminal ileum In addition, these agents increase mucosal permeability and stimulate motility Disruption of normal Na1/K1-ATPase activity results in the net secretion of fluid and electrolytes This mechanism is the final common pathway in a number of secretory diarrheal states, such as ischemia-reperfusion, cholera, enterotoxigenic E coli, Salmonella, Campylobacter jejuni, and Clostridium perfringens, which appear to act through second messenger pathways via their toxins.24 Rotavirus appears to have several mechanisms of causing diarrhea The first appears to be a mechanism of increasing Cl– secretion with a resulting secretory diarrhea mediated by calcium (Ca21), a different mechanism than bacteria-mediated diarrheal diseases The second is an osmotic diarrhea caused by villus destruction and resultant malabsorption In addition, the effects of various paracrine and endocrine mediators alter intestinal adenyl cyclase activity, leading to changes in electrolyte and water balance Gastric Acid Hydrochloric acid secretion by the gastric parietal cell is necessary for pepsinogen activation (pH ,5.0) and to reduce bacterial colonization H1 and HCO3– are produced from water and carbon dioxide by the action of carbonic anhydrase within the parietal cell HCO3– is secreted into the bloodstream in exchange for Cl– at the basolateral membrane Cl– and K1 are both secreted along with H1 across the apical membrane against a large concentration gradient This is an active process, mainly due to the action of the proton pump, H1/K1-ATPase, which is the final step in gastric acid secretion and the site of action of proton pump inhibitor (PPI) antacids Histamine, gastrin, and acetylcholine are the main stimuli for gastric acid secretion Gastric distension, dietary amino acids, and amines stimulate gastrin hormone secretion by G-cells located in the gastric antrum Gastrin is the most potent endogenous stimulant of gastric acid secretion and stimulates release of histamine by the enterochromaffin-like cells Histamine then binds to histamine-2 (H2) receptors on parietal cells, leading to acid secretion Prostaglandins and somatostatin have an inhibitory effect on gastric acid secretion via specific receptors located on the parietal cell H2-receptor antagonists (H2RAs) block histamine-mediated gastric acid secretion found in postprandial acid secretion, Zollinger-Ellison syndrome, and other disorders associated with hypergastrinemia PPIs block gastric acid secretion by inhibiting the parietal cell H1/K1-ATPase They bind irreversibly to the enzyme and subsequent secretion of acid can occur only with the synthesis of new proton pump enzyme, a process that takes 12 to 24 hours For these reasons, PPIs have revolutionized gastric acid suppression therapy H2RAs and PPIs are equally effective in many patients for preventing bleeding in the upper part of the GI tract in patients receiving mechanical ventilation.28 Studies have shown that some oral PPIs suppress acid in ICU patients to a greater extent than IV PPIs ICU patients at risk of stress ulcer– related bleeding are most likely to benefit from prophylaxis,29 although the increased presence of gram-negative organisms in the upper GI tract due to acid-suppressing therapies has been implicated in ventilator-associated pneumonias.30 Intestinal Motility The intestines are sometimes referred to as the second brain in the body owing to the intricate neural network that allows for coordinated peristalsis, creation of suitable neurohumoral reflexes to induce digestive enzyme secretion, mixing of luminal contents to enhance absorption, and elimination of debris The enteric nervous system is contained in the intestinal wall and consists of sensory and motor neurons as well as interneurons that coordinate activity through similar mechanisms and neurotransmitters found in the central nervous system.31 The enteric nervous system can function autonomously but receives significant modulating input from the sympathetic and parasympathetic nervous system.19 Pain receptors generally respond to stretch as occurs when pressure builds up within the lumen Chronic inflammatory stimulation, as seen in inflammatory bowel disease or graft-versus-host disease of the gut, may lead to central sensitization and chronic intestinal pain and spasm.31 Dysmotility is commonly seen in critically ill patients due to intestinal ischemia and drug effects The intensivist will often be confronted with the temporary inability to use the gut for nutrition or medication administration However, in a small number of pediatric patients, many of whom have chronic neurodevelopmental disability or central nervous system dysfunction, intestinal pseudo-obstruction may develop and become permanent.32,33 While acquired intestinal failure due to dysmotility is rare, it represents a major ethical dilemma, because long-term total parenteral nutrition is often the only solution to preserve life in a patient whose quality of life may be limited Pancreas The pancreas has both endocrine and exocrine functions and acts in concert with the liver to regulate blood glucose levels Endocrine-secreting cells of the pancreas are aggregated within the islets of Langerhans There are approximately 1,000,000 islets in the human pancreas Four distinct cell types in the islets that serve the endocrine function are B cells, which secrete insulin (50%–80%); CHAPTER 94 Gastrointestinal Structure and Function A cells, which secrete glucagon (5%–20%); D cells, which secrete somatostatin (5%); and PP cells, which secrete pancreatic polypeptide.34 Branches of the celiac, superior mesenteric, and splenic arteries supply the pancreas Venous drainage is via the pancreaticoduodenal veins, splenic veins, and ultimately the portal vein, providing direct hormonal influence over hepatic metabolism Both parasympathetic and sympathetic innervation of the pancreas occurs by means of the vagal and abdominal plexuses, respectively The vagal innervation of acini, islets, and ducts facilitates secretory function, whereas sympathetic innervation occurs primarily to vascular structures Functional ectopic pancreatic tissue may be found commonly throughout the upper GI tract Pancreatic Exocrine Secretory Function The functional unit of the exocrine pancreas is the acinus, composed of specialized cells containing secretory granules that drain into ductules leading to the pancreatic duct In contrast to the pancreatic endocrine cells that demonstrate specialized function, each acinar cell is capable of secreting all pancreatic digestive enzymes The basolateral membrane has receptors for hormones and neurotransmitters that stimulate pancreatic secretion of the digestive enzymes stored in zymogen granules near the apical membrane of each acinar cell Ultimately, the pancreatic duct joins with the common bile duct and drains into the duodenum through the ampulla of Vater Anatomic variation exists such that 74% of people have a common channel, while 19% have a separate opening Pancreatic juice is an isotonic fluid, containing primarily Na1, K1, Cl–, and HCO3– The total volume of secretion is 2.5 L daily CFTR is the main channel for Cl– secretion in the pancreas and is involved in other ion transport, which has relevance in patients with cystic fibrosis Secretion of HCO3– and water is mediated through the actions of the gut hormones secretin, cholecystokinin, and VIP Stimulation of the vagus nerves or the administration of acetylcholine induces digestive enzyme secretion These effects may be blocked with atropine There are four phases of pancreatic secretion Basal secretion represents approximately 2% of the potential maximum HCO3– The cephalic phase is mediated by the vagal nerves in response to the sight and smell of food The gastric phase consists of secretion of a protein-rich pancreatic juice of low volume and HCO3– occurs following either distention of the stomach or after the ingestion of food The intestinal phase is characterized by marked output of digestive enzymes, fluid, and HCO3–.35,36 The presence of HCO3– is essential to achieve an optimal pH (pH 5) for pancreatic digestive enzyme activity and to ensure solubility of bile salts In addition to HCO3–, the primary secretory products of the exocrine pancreas are amylase, lipase, and the proteases The secondary digestive enzymes consist of nucleases, colipase, and lecithinase Cholecystokinin (CCK) is the major humoral mediator of meal-stimulated enzyme secretion It is released from the small intestinal mucosa in response to presence of fat, protein, and starch, related to total load rather than luminal concentration CCK activates afferent neurons in duodenal mucosa, which leads to secretin release via a vasovagal reflex Inhibitors of exocrine pancreatic secretion include somatostatin, pancreatic polypeptide, and peptide YY Octreotide, a somatostatin analog, has been used for its antisecretory effect in clinical management of pancreatic pseudocysts and fistulae, but its use in acute or chronic pancreatitis remains controversial It is commonly used for chylous 1135 pleural effusions and upper GI bleeding Inflammation of the pancreas (acute pancreatitis) both from infectious and noninfectious causes can produce a dramatic systemic inflammatory response resulting in generalized permeability changes and acute lung injury Hepatobiliary System Examination A complete physical examination of all children admitted to an ICU should include inspection, palpation, and auscultation of the abdomen, with particular attention to hepatic or splenic enlargement, distended superficial veins, and abdominal masses; the characteristics of the bowel sounds; and, finally, visual inspection of the perianal region for signs of trauma, fistulae, and venous distension Palpation of the liver provides information about the hepatobiliary tract as well as function of the right side of the heart Normally, the liver is palpable approximately to cm below the right costal margin in the midclavicular line However, assessment of liver span, and not palpation alone, is the only reliable nonradiologic method for determining liver size Liver span is determined by percussion, palpation, and auscultation along the right midclavicular line with the patient supine and breathing quietly The dullness of the upper border is determined by percussion Palpation or auscultation is most commonly used to establish the lower border The liver span increases with body weight and age in both sexes, ranging from 4.5 to 5.0 cm at week of age to to cm in boys and 6.0 to 6.5 cm in girls by age 12 years.37 Examination of the liver and abdomen should note consistency, contour, tenderness, the presence of any masses or bruits, and assessment of spleen size.38 Splenomegaly is denoted as a spleen that is palpable more than cm below the costal margin.39 Documentation of the presence of ascites and stigmata of chronic liver disease is important Ascites may be suggested by a history of recent increases in weight, on physical examination by shifting dullness or fluid wave, or by abdominal imaging—ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI).38 Tenderness over the liver suggests inflammation or stretching of the fibrous capsule through rapid enlargement Conditions associated with downward displacement of a normal liver include hyperinflated lungs, pneumothorax, retroperitoneal masses, and subdiaphragmatic abscess End-stage liver disease and cirrhosis are associated with a reduced liver span corresponding to decreased hepatic cell mass The spleen tip may be palpable normally in children, especially during inspiration However, enlargement of the spleen generally represents elevated portal venous pressures or invasive processes such as sequestration, malignancy, extramedullary hematopoiesis, or hyperplasia of the reticuloendothelial system.39 Anatomy, Structure, and Function The liver is the largest organ in the body It is composed of 60% hepatocytes, approximately 17% to 20% endothelial cells and Kupffer cells (reticuloendothelial cells), 3% to 5% bile ducts, and 1% hepatic stellate cells (HSCs) and oval cells The liver has a dual vascular supply derived from the hepatic artery branches of the celiac axis, providing about 30% of the blood supply, and the portal vein, providing approximately 70% Innervation of the liver is by the parasympathetic branches derived from both vagi 1136 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition and sympathetic branches, which also carry afferent fibers derived from thoracic segments Denervation of the liver, such as seen after liver transplantation, does not affect function The liver lobule, the functional unit of the liver, is composed of interconnected hepatocytes (hepatic plates) to cells thick and 20 to 25 cells in length separated by a venous sinusoidal space and radiating around the central vein like spokes in wheel The narrow tissue space between the endothelial cells and hepatic plates, the space of Disse, connects with lymphatic vessels in the interlobular septa Hepatic sinusoidal endothelial cells are flat cells that not form intracellular junctions and overlap one another They are fenestrated, allowing plasma to enter into the space of Disse and come into direct contact with the surface of hepatocytes.40 This facilitates bidirectional exchange between the hepatocytes and sinusoidal space Macrophage-derived Kupffer cells line the sinusoidal space These cells have a phagocytic function and contribute to the hepatic inflammatory response Kupffer cells influence hepatocyte responses through paracrine effects following activation HSCs, also known as ito cells, lie within the space of Disse HSCs serve as the hepatic storage site of vitamin A, are effectors of fibrogenesis, and play a role in extracellular matrix remodeling during recovery from injury Chronic activation and proliferation of HSCs may lead to noncirrhotic portal hypertension, fibrosis, and cirrhosis.41 Bile canaliculi lie between adjacent hepatocytes and drain into small terminal bile ducts, which successively drain into larger bile ductules, intralobular bile ducts, and, eventually, the extrahepatic bile ducts Tight junctions between the hepatocytes at the canalicular space permit unidirectional transport of substances from the hepatocytes into the canalicular space Several different carriers, receptors, and transport proteins facilitate movement of compounds across the sinusoidal, hepatocyte, and canalicular membranes Alkaline phosphatase, leucine aminopeptidase, and g-glutamyl transpeptidase are transaminase enzymes selectively localized in the bile canaliculi that are released with injury and serve as markers of biliary disease (eTable 94.2) The microcirculatory path within the lobules leads along a declining hydrostatic pressure gradient from the terminal hepatic arterioles and portal venules within the portal triad toward the central vein representing the beginning of the hepatic vein, resulting conceptually in three hepatocyte functional zones Zone hepatocytes closest to the portal triad are exposed to sinusoidal blood containing the highest concentration of solutes (nutrients, pancreatic hormones) and oxygen In contrast, zones and represent hepatocytes more distant from the portal blood supply and are exposed to a declining oxygen and solute concentration In addition, zone hepatocytes actively participate in drug metabolism and disposition Ischemic injury and drug hepatotoxicity impacts zone hepatocytes to the greatest degree.42 Following irreversible injury in zone 3, fibrosis occurs in a pattern bridging the terminal hepatic venules, leading to the stellate pattern of bridging fibrosis seen histologically Portal Circulation The portal venous system drains the intestines, pancreas, and spleen with numerous collateral anastomoses to other venous beds of the abdomen There is a mixing of portal and systemic blood circulation within the sinusoids; all the blood eventually drains from the liver via the hepatic veins to the inferior vena cava The liver has a high blood flow (27% of the resting cardiac output) and low vascular resistance The portal pressure gradient (PPG) is the pressure difference between the inferior vena cava and the portal vein The average PPG is to mm Hg Portal hypertension is defined as a PPG between and 10 mm Hg A PPG greater than 10 mm Hg carries risk for development of esophageal varices, and a PPG greater than 12 mm Hg predisposes toward ascites formation.39 Obstruction of the portal venous drainage at any level leads to portal hypertension Portal hypertension may be classified as prehepatic, intrahepatic, or posthepatic according to the level at which the obstruction to flow occurs The determination of the location of obstruction is critical for instituting appropriate therapy Ascites formation is multifactorial.38 The central event in ascites formation in cirrhosis is splanchnic arterial vasodilation secondary to portal hypertension This creates an increase in capillary pressure due to increased blood inflow, leading to leakage of fluids based on classic Starling forces Additionally, impairment of systemic hemodynamics and renal function leads to sodium and water retention with intravascular volume expansion Ascites may form in the absence of portal hypertension as the result of low plasma oncotic pressure associated with malnutrition, with renal or enteral protein losses, or through impaired thoracic duct lymph drainage Rarely, arterial-portal venous malformations may lead to portal hypertension as a result of excess portal blood flow and must be investigated when other causes of ascites are not found One additional factor predisposing to ascites is an elevated central venous pressure that increases formation and impairs resorption of interstitial fluid often associated with generalized anasarca or other signs of right heart failure.38 Prolonged portal hypertension produces esophageal and gastric varices Variceal wall tension is a function of transmural pressure across the varix between the variceal and esophageal lumen Variceal bleeding occurs when the wall tension exceeds variceal wall strength Significant bleeding may predispose to encephalopathy in patients with cirrhosis through decreased hepatic perfusion and increased ammonia generated by swallowed blood Vasoactive drugs, such as octreotide, act to reduce splanchnic blood flow, reducing portal venous inflow, thus reducing portal pressure Octreotide has been used safely to slow GI bleeding in patients with varices and portal hypertension.43 Hepatic Function The function of the liver may be broadly characterized in terms of (1) production of substances uniquely made in the liver; (2) the degradation, elimination, and detoxification of biological materials; (3) the maintenance of biochemical homeostasis; and (4) storage of nutritional materials The liver occupies an ideal place in the scheme of digestion Hepatocytes are exposed to large quantities of absorbed nutrients after ingestion of a meal with 20% of the total absorbed nitrogen used for hepatic protein synthesis In addition, the liver receives pancreatic drainage leading to regulatory effects on hepatocyte function Of the large number of plasma proteins synthesized by the liver, several are of major significance in the ICU and are discussed next Albumin has a half-life of 18 to 20 days and is a significant contributor to colloid oncotic pressure.44 It is synthesized solely in the liver; decreased serum levels may predispose to edema formation and decreased binding of bilirubin, calcium, xenobiotics, and other highly protein-bound molecules Low serum albumin levels can be secondary to impaired synthesis from protein-calorie 1136.e1 eTABLE Pattern of Biochemical Tests Based on 94.2 Category of Liver Disease Biochemical Test Hepatocellular Necrosis Cholestasis Infiltrative Process ALT, AST 11 to 111 to to ALK, GGT to 11 to 111 Total/conjugated bilirubin to 111 to 111 to PT Prolonged Prolonged; responsive to vitamin K Albumin Decreased in chronic disorders Decreased in chronic disorders Cholesterol 0 to 111 Bile acids to 111 to 111 0, normal; to 111, degrees of elevation ALK, Alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; GGT, g-glutamyltransferase; PT, prothrombin time ... 94.2) The microcirculatory path within the lobules leads along a declining hydrostatic pressure gradient from the terminal hepatic arterioles and portal venules within the portal triad toward the... Disruption of normal Na1/K1-ATPase activity results in the net secretion of fluid and electrolytes This mechanism is the final common pathway in a number of secretory diarrheal states, such as ischemia-reperfusion,... colonization H1 and HCO3– are produced from water and carbon dioxide by the action of carbonic anhydrase within the parietal cell HCO3– is secreted into the bloodstream in exchange for Cl– at the basolateral