Endocrine Pancreatic Tumors: Ultrastructure

Total Page:16

File Type:pdf, Size:1020Kb

Endocrine Pancreatic Tumors: Ultrastructure ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 1 Copyright© 1980, Institute for Clinical Science, Inc. Endocrine Pancreatic Tumors: Ultrastructure MERY KOSTIANOVSKY, M.D. Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107 ABSTRACT Endocrine pancreatic tumors are frequently multicellular and produce several hormones and peptides. A review of the basic concepts of hormone secretion, pancreatic islet cell composition and ultrastructural make-up of tumors is presented. The importance of correlating ultrastructural, immuno- cytochemical and biochemical studies of these tumors is emphasized. Introduction Morphofunctional Aspects of Pancreatic Islets During the last few years a great amount of information was accumulated regarding At the present time four different types the mechanisms of synthesis, storage and of cells have been described in the pan­ release of hormones.14,28,31 The use of ex­ creatic islets,17,33 each having a specific perimental in vitro m odels21,25,26,28 was secretory product (table I). A variety of very helpful in clarifying the participation other cells possibly exists, although of different organelles in the biosynthesis, further identification is awaited. By light cellular “packaging” and emyocytosis of microscopy, it is not possible to distin­ the secretory products. In a review, Lacy31 guish one type of cell from the other. has proposed a working model for hor­ Histochemical procedures are of help, mone secretion, describing the sim­ however, and B cells are easily stained ilarities between different endocrine with aldehyde fuchsin. The dicferent pro­ glands. Some of this information was ob­ cedures and empiric nature oi the silver tained through the studies of endocrine stain22 added confusion in the nomen­ pancreatic tumors as in the case of the clature of the cells (as seen in table I) discovery of pro-insulin in a beta cell where the same cell has been described adenoma.62 The purpose of this paper is to by different names. illustrate the ultrastructural observations Immunofluorescent studies have dem­ of pancreatic tumors and to review the onstrated that B cells contain insulin. A literature. Attempts are made to correlate, cells contain glucagon and somatostatin wherever possible, the ultrastructural was localized in the D cells.57 Although, morphology of these tumors with normal some investigators20 found gastrin in the pancreatic islets cells and their possible D cells, this finding was not corroborated histogenesis. by others44 and the cell source of gastrin in 65 0091-7370/0100-0065 $01.80© Institute for Clinical Science, Inc. 66 KOSTIANOVSKY T A B L E I Normal Islet Cell Population Type of Cell & Secretory Frequency Electron Microscopy Topographic Product (Percent} Histochemistry Size Shape Localization B cells (B) Aldehyde 200 - 250 nm Insulin fuschsin + A cells (&2> 20 - 25 Argyrophilic 250 - 200 nm Glucagon reaction Grimelius + Argyrophilic 300 - 350 nm Somatostatin reaction Uellerström and Heilman Human pancreatic Not present Grimelius + 100 - 150 nm polypetide in every 4th type islet Acinar cells Ductal cells A fifth type of cell (D1) is omitted since the relation with V.I.P. is still in dispute. the pancreatic islets is not known. In addi­ a central homogenous cell population as tion, a fourth type of cell containing small composed of B cells, and a peripheral granules54 has been shown to store human zone of heterogenous cell population con­ pancreatic polypeptide, (HPP), a secre­ taining A, D and HPP cells or the fourth tory product whose physiological role has type of cells. These authors suggested that not yet been determined.1 this cellular distribution has functional Recently, a fifth type of cell (Dl) was implications. Since each cell produces a described, and there is some indication hormone which is influencing the which correlates this cell with the produc­ neighboring cells in related functions, it tion of vasoactive intestinal polypeptide was hypothesized that this action is local (VIP) or VIP-related molecule.60 In addi­ or “paracrine” in nature, without entering tion, cells similar to the enterochromaffin the general circulation.50 The finding of gastro-intestinal cells were rarely re­ junctional intercellular attachments of ported in human islets.6 Except for the B tight and gap type66 reinforced their and A cells, most of the cells described in hypothesis. the pancreatic islets are also present in the Intracellular Aspects of gastro-intestinal tract. This morphological the Secretory Process and functional overlap between gut endocrinology and pancreatic islets Hormonal synthesis occurs in the rough emphasizes the common embryological endoplasmic reticulum in the form of origin and probably functional inter­ pro-hormones (pro-insulin, pro-gluca- relationship. gon) and by an energy requiring mecha­ Unger et al63 have described a topo­ nism transferred to the Golgi-Complex. In graphic localization of the different cells the Golgi-Complex, the big molecules are in the pancreatic islets. Using immuno- split by an enzymatic mechanism and histochemical methods,50 Orci described converted to the mature hormone. A ENDOCRINE PANCREATIC TUMORS ULTRASTRUCTURE 6 7 membranous sac derived from the Golgi abundance of granules by electron mi­ Complex is added35 and the final product croscopy without evidence of hormonal is condensed in a visible form.25 From the secretion clinically. In vitro studies of Golgi Complex, the mature secretory insulinoma corroborated the assumption products are channeled to the periphery that these tumor cells have the capacity for of the cells where, with the participation a higher turnover of proinsulin and in­ of the microtubular-microfilamentous sulin compared to normal beta cells. system, secretion takes place. The secre­ Hence, insulinoma cells may display a tory mechanism occurs by fusing the decrease storage capacity.10 granule membrane with the plasma membrane of the cell in a process called The Histogenesis of the emiocytosis or exocytosis without loss Pancreatic Islet Cell Tumors of granular membrane (figure 1). The understanding of the secretory The histogenesis of pancreatic islet cell process in the normal cell is important, tumors have been the source of con­ since the neoplastic cell might suffer al­ troversy. Two main theories exist regard­ terations in the different steps of this nor­ ing the cell of origin, one claiming an mal process.19 Tumors usually secrete endodermal origin from a putative pluri- hormone in an “autonomous” fashion un­ potential ductal cell.37 The authors based responsive of stimulatory or inhibitory their hypothesis on morphological obser­ mechanisms. There are few cases in the vations55 of fetal pancreas, as well as on literature of insulinoma retaining the comparative endocrinological studies.12 normal capacity to respond to different The second theory proposed by concentrations of glucose.58 Certain Pearse53 places the islet cells as a part of tumors secrete mainly the immature a big family of cells which appear to be of secretory product as in the case of an neuroectodermal derivation having insulinoma and glucagonoma which pro­ APUD(Amine content and/or Amine Pre­ duced pro-insulin and pro-glucagon, re­ cursor Uptake and Decarboxylation) spectively.12 This would explain the var­ characteristics. Their theory is based on iability of the histochemical reactions in cytochemistry and ultrastructural endocrine pancreatic tumors and the studies52 (figure 2). M icro tu bular m ic ro f il am e nts s y s te m C a p illa ry F I G U R E 1. Schem atic representation of the se­ S e c r e to ry G ra n u le quence of events leading to endocrine secretion. Fndothelial R.E.R. = Rough endo­ CeU plasmic reticulum. N u cleu s B asal M em b ra n e 68 KOSTIANOVSKY HISTOGENESIS OF PANCREATIC ENDOCRINE TUMORS logical behavior of these tumors could be understood better and possible tumor Endodermal Origin Ectodermal Origin markers could be recognized. These (neural crest) tumor markers could be of help in diag­ I i nosis, especially in non-functional tu­ Pluripotential Amine Precursor mors, and in monitoring the treatment of Ductal Cells Uptake and Decarboxylation possible recurrences. Cell Series One such study56 demonstrated in­ I I creased pancreatic polypeptide levels in Pancreatic Endocrine Pancreatic Endocrine Tumors Tumors plasma of patients with different types of pancreatic endocrine neoplasms. How­ F ig u r e 2. A.P.U.D. = Amine Precursor l/ptake ever, it was recently shown in many cases and Decarboxylation (see references 52 and 53). that the increase of pancreatic polypep­ tide levels are due to islet hyperplasia in the peripancreatic region and not to the Creutzfeld recently8,9 described a type presence of pancreatic polypeptide cells in of cell found in different types of pancrea­ the tumor itself.38 tic endocrine tumors which has atypical Several clinical syndromes have been secretory granules unlike any other type produced by endocrine pancreatic tu­ of cell in the normal islet. He concluded mors. Ultrastructurally, these tumors con­ that these cells may represent a precursor tain a variety of granulated and agranu- or stem pluripotential cell type, present lated cell types. The prevailing cell type also in cases of ductular proliferation. in most cases correlated with the clinical Ductular proliferation and nesidio­ symptoms of hormone secretion (tables II blastosis (neoformation of islets) have and III). been recently described in the peritu- moral pancreatic tissue.9,39 Experimental
Recommended publications
  • Cholecystokinin Expression in the Developing and Regenerating Pancreas and Intestine
    233 Cholecystokinin expression in the developing and regenerating pancreas and intestine G Liu, S V Pakala, D Gu, T Krahl, L Mocnik and N Sarvetnick Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (Requests for offprints should be addressed to N Sarvetnick; Email: [email protected]) Abstract In developmental terms, the endocrine system of neither NOD mice continued this pattern. By contrast, in IFN- the gut nor the pancreatic islets has been characterized transgenic mice, CCK expression was suppressed from fully. Little is known about the involvement of cholecysto- birth to 3 months of age in the pancreata but not intestines. kinin (CCK), a gut hormone, involved in regulating the However, by 5 months of age, CCK expression appeared secretion of pancreatic hormones, and pancreatic growth. in the regenerating pancreatic ductal region of IFN- Here, we tracked CCK-expressing cells in the intestines transgenic mice. In the intestine, CCK expression per- and pancreata of normal mice (BALB/c), Non Obese sisted from fetus to adulthood and was not influenced Diabetic (NOD) mice and interferon (IFN)- transgenic by IFN-. Intestinal cells expressing CCK did not mice, which exhibit pancreatic regeneration, during em- co-express glucagon, suggesting that these cells are bryonic development, the postnatal period and adulthood. phenotypically distinct from CCK-expressing cells in We also questioned whether IFN- influences the expres- the pancreatic islets, and the effect of IFN- on sion of CCK. The results from embryonic day 16 showed CCK varies depending upon the cytokine’s specific that all three strains had CCK in the acinar region of microenvironment.
    [Show full text]
  • Reference ID: 4125998
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Determine the number of vials to be reconstituted based on the patient’s These highlights do not include all the information needed to use weight and prescribed dose (2.2) ® CHIRHOSTIM safely and effectively. See full prescribing information for • ChiRhoStim® must be reconstituted with 0.9% Sodium Chloride CHIRHOSTIM®. Injection prior to administration (2.2) • See full prescribing information for complete information on exocrine ® CHIRHOSTIM (human secretin) for injection, for intravenous use test methods (2.3) Initial U.S. Approval: 2004 -------------------------RECENT MAJOR CHANGES----------------------------­ ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ Dosage and Administration (2.1) 07/2017 For injection: 16 mcg or 40 mcg of human secretin as a lyophilized powder in Contraindications, removed (4) 07/2017 single-dose vial for reconstitution (3) Warnings and Precautions (5.1, 5.2) 07/2017 -------------------------------CONTRAINDICATIONS-----------------------------­ -------------------------INDICATIONS AND USAGE----------------------------- None (4) ChiRhoStim® is a secretin class hormone indicated for stimulation of: • pancreatic secretions, including bicarbonate, to aid in the diagnosis of -----------------------WARNINGS AND PRECAUTIONS-----------------------­ exocrine pancreas dysfunction (1) • Hyporesponse to Secretin Stimulation Testing in Patients with • gastrin secretion to aid in the diagnosis of gastrinoma (1) Vagotomy, Inflammatory Bowel Disease or Receiving
    [Show full text]
  • Digestive System Physiology of the Pancreas
    Digestive System Physiology of the pancreas Dr. Hana Alzamil Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin What are the types of glands? Anatomy of pancreas Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Histology of the Pancreas Acini ◦ Exocrine ◦ 99% of gland Islets of Langerhans ◦ Endocrine ◦ 1% of gland Secretory function of pancreas Acinar and ductal cells in the exocrine pancreas form a close functional unit. Pancreatic acini secrete the pancreatic digestive enzymes. The ductal cells secrete large volumes of sodium bicarbonate solution The combined product of enzymes and sodium bicarbonate solution then flows through a long pancreatic duct Pancreatic duct joins the common hepatic duct to form hepatopancreatic ampulla The ampulla empties its content through papilla of vater which is surrounded by sphincter of oddi Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Composition of Pancreatic Juice Contains ◦ Water ◦ Sodium bicarbonate ◦ Digestive enzymes Pancreatic amylase pancreatic lipase Pancreatic nucleases Pancreatic proteases Functions of pancreatic secretion Fluid (pH from 7.6 to 9.0) ◦ acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen ◦ Neutralizes acidic gastric secretion Enzymes ◦
    [Show full text]
  • Normal Pancreatic Function 1. What Are the Functions of the Pancreas?
    Normal Pancreatic Function Stephen J. Pandol Cedars-Sinai Medical Center and Department of Veterans Affairs Los Angeles, California USA [email protected] Version 1.0, June 13, 2015 [DOI: 10.3998/panc.2015.17] 1. What are the functions of the This chapter presents processes underlying the functions of the exocrine pancreas with pancreas? references to how specific abnormalities of the The pancreas has both exocrine and endocrine pancreas can lead to disease states. function. This chapter is devoted to the exocrine functions of the pancreas. The exocrine function 2. Where is the pancreas located? is devoted to secretion of digestive enzymes, ions and water into the intestine of the gastrointestinal The illustration in Figure 1 demonstrates the (GI) tract. The digestive enzymes are necessary anatomical relationships between the pancreas for converting a meal into molecules that can be and organs surrounding it in the abdomen. The absorbed across the surface lining of the GI tract regions of the pancreas are the head, body, tail into the body. Of note, there are digestive and uncinate process (Figure 2). The distal end enzymes secreted by our salivary glands, of the common bile duct passes through the head stomach and surface epithelium of the GI tract of the pancreas and joins the pancreatic duct as it that also contribute to digestion of a meal. enters the intestine (Figure 2). Because the bile However, the exocrine pancreas is necessary for duct passes through the pancreas before entering most of the digestion of a meal and without it the intestine, diseases of the pancreas such as a there is a substantial loss of digestion that results cancer at the head of the pancreas or swelling in malnutrition.
    [Show full text]
  • Physiology of the Pancreas
    Te xt . Only in Females’ slide . Only in Males’ slides . Important Lecture . Numbers No.4 . Doctor notes . Notes and explanation “Be The Best Version Of You” 1 We recommended you to study Histology & Anatomy of pancreas first. Physiology of the pancreas Objectives: 1-Functional Anatomy. 2-Major components of pancreatic juice and their physiologic roles. 3-Cellular mechanisms of bicarbonate secretion. 4-Cellular mechanisms of enzyme secretion. 5-Activation of pancreatic enzymes. 6-Hormonal & neural regulation of pancreatic secretion. 7-Potentiation of the secretory response. 8- Pancreatic acini. 2 Functional Anatomy & Histology of the Pancreas Today we are concern about the digestive role of pancreas not the endocrine role, the endocrine part represent 95% of its Extra function, the left 5% represent the digestive part. Functional Anatomy: The pancreas, which lies parallel to and beneath the stomach is a large compound gland with most of its internal structure similar to that of the salivary glands (Look like them so they have both acinar cells and tubal cells) Islet of langerhans in the pancreas: the pancreas, in addition to its digestive functions, secretes two important hormones: Insulin (beta cells, 60%). Islet of Langerhans have different type of cells (alpha, beta and delta) and If we go and get a cross section view of the every single one of them can release a certain hormone. pancreatic tissue. We can see many acinar Glucagon (alpha cells, ~25%). cells and in the middle we have a ductal That are crucial for normal regulation of glucose, lipid, and protein metabolism. Also somatostatin is lumen. secreted by delta cells (form ~10% of islets’s cells).
    [Show full text]
  • Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: an Etiopathogenetic Hypothesis
    JOP. J Pancreas (Online) 2005; 6(2):122-127. EDITORIAL Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis Giorgio Talamini Gastroenterology and Endoscopy Service, University of Verona. Verona, Italy Summary duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejuno- Chronic pancreatitis patients have an stomy are probably less critically affected increased risk of developing pancreatic because secretions transit, at least in part, via cancer. The cause of this increase has yet to the papilla. be fully explained but smoking and If the duodenal acidity hypothesis proves inflammation may play an important role. To correct, then, in addition to stopping smoking, these, we must now add a new potential risk reduction of duodenal acid load in patients factor, namely duodenal acidity. Patients with with pancreatic insufficiency may help chronic pancreatitis very often present decrease the risk of pancreatic cancer. pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in Chronic pancreatitis (CP) patients have an chronic pancreas patients with pancreatic increased risk of developing pancreatic cancer insufficiency has a normal concentration of s- [1, 2]. The cause of this increase has yet to be cells and, therefore, the production of secretin fully explained and various hypotheses are is preserved. Pancreatic ductal cells are being explored [3, 4, 5, 6, 7]. Nevertheless, largely responsible for the amount of smoking unquestionably plays an important bicarbonate and water secretion in response to role [4, 8, 9] because the great majority of CP secretin stimulation.
    [Show full text]
  • Gastrointestinal Physiology 191
    98761_Ch06 5/7/10 6:27 PM Page 190 190 Board Review Series: Physiology Gastrointestinal chapter 6 Physiology I. STRUCTURE AND INNERVATION OF THE GASTROINTESTINAL TRACT A. Structure of the gastrointestinal (GI) tract (Figure 6-1) 1. Epithelial cells ■ are specialized in different parts of the GI tract for secretion or absorption. 2. Muscularis mucosa ■ Contraction causes a change in the surface area for secretion or absorption. 3. Circular muscle ■ Contraction causes a decrease in diameter of the lumen of the GI tract. 4. Longitudinal muscle ■ Contraction causes shortening of a segment of the GI tract. 5. Submucosal plexus (Meissner’s plexus) and myenteric plexus ■ comprise the enteric nervous system of the GI tract. ■ integrate and coordinate the motility, secretory, and endocrine functions of the GI tract. B. Innervation of the GI tract ■ The autonomic nervous system (ANS) of the GI tract comprises both extrinsic and intrin- sic nervous systems. 1. Extrinsic innervation (parasympathetic and sympathetic nervous systems) ■ Efferent fibers carry information from the brain stem and spinal cord to the GI tract. ■ Afferent fibers carry sensory information from chemoreceptors and mechanoreceptors in the GI tract to the brain stem and spinal cord. a. Parasympathetic nervous system ■ is usually excitatory on the functions of the GI tract. ■ is carried via the vagus and pelvic nerves. ■ Preganglionic parasympathetic fibers synapse in the myenteric and submucosal plexuses. ■ Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 190 98761_Ch06 5/7/10 6:27 PM Page 191 Chapter 6 Gastrointestinal Physiology 191 Epithelial cells, endocrine cells, and receptor cells Lamina propria Muscularis mucosae Submucosal plexus Circular muscle Myenteric plexus Longitudinal muscle Serosa FIGURE 6-1 Structure of the gastrointestinal tract.
    [Show full text]
  • Pancreas Anatomy, Physiology and Genetics
    GI Board Review 2014 Pancreas: A&P, Genetics PANCREAS ANATOMY, PHYSIOLOGY AND GENETICS David C Whitcomb MD PhD Professor of Medicine, Cell Biology & Physiology and Human Genetics Chief, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh Outline Overview Pancreatic Anatomy - Gross anatomy - Microanatomy Pancreatic Physiology - Acinar cell - Duct cell - Neurohormonal control - Meals and system integration Pancreatic Genetics - Mendelian disorders - Complex disorders - Genetic test in interpretation Questions References GI Board Review 2014 Pancreas: A&P, Genetics 1. Overview The pancreas is a vital organ that plays a central role in digestion and metabolism of nutrients. Major functions of the pancreas include: secretion of digestive enzymes into the duodenum for the breakdown of complex proteins, carbohydrates, lipids and nucleic acids, secretion of bicarbonate into the duodenum in order to neutralize the acidic chyme exiting the stomach, and secretion of islet cell hormones into the circulation to control systemic metabolism of nutrients after absorption. 2. Gross Anatomy A. Relationship of the Pancreas to other systems In the adult the pancreas lies behind the peritoneum of the posterior abdominal wall and is in an oblique orientation. The head of the pancreas is flanked by the duodenum on the right. The body is ventral to the 2nd-4th lumbar spine (making it susceptible to blunt trauma) and dorsal to the stomach. The blood supply to the pancreas can be quite variable, but comes, in general from branches of the gastroduodenal, superior mesenteric and splenic arteries. These form anterior and posterior arcades which supply the pancreatic head. The body and tail are supplied predominately by branches of the splenic artery.
    [Show full text]
  • Delta Cell Reprogramming During Mouse Pregnancy
    Aus dem Paul-Langerhans Institut Dresden Direktor: Prof. Dr. Michele Solimena Delta cell reprogramming during mouse pregnancy Dissertationsschrift zur Erlangung des akademischen Grades Doktor der Biomedizin Doctor rerum medicinalium (Dr. rer. medic.) vorgelegt der Medizinischen Fakultät Carl Gustav Carus der Technischen Universität Dresden von Julia Katharina Panzer geb. Stertmann aus Münster Dresden 2018 1. Gutachter: 2. Gutachter: Tag der mündlichen Prüfung: gez.:____________________________ Vorsitzender der Promotionskomission Success is the ability to go from one failure to another with no loss of enthusiasm. – Winston Churchill Table of contents 1 Introduction .............................................................................................. 1 1.1 The Pancreas ...................................................................................................... 1 1.1.1 Anatomy ............................................................................................................................... 1 1.1.2 Development ....................................................................................................................... 2 1.2 Islets of Langerhans ............................................................................................ 6 1.2.1 Islet architecture .................................................................................................................. 6 1.2.2 Islet cell function .................................................................................................................
    [Show full text]
  • EN GAST IND.Pdf
    EN_GAST_IND.QXD 08/31/2005 11:31 AM Page 825 Index The bold letter t or f following a page reference indicates that the information appears on that page only in a table or figure, respectively. abdomen: examination of, 41–8; regions, 43f acetylcholine, 145, 190t abdominal aortic reconstruction, 275t acetyl-CoA, 53 abdominal mass: about, 37–40; with colon N-acetylcysteine, 582 cancer, 365t; and constipation, 386; with achalasia, 118f; about, 121–2; Crohn’s disease, 314, 342t; with cystic cricopharyngeal, 117t, 118; esophageal, fibrosis, 456; GI tract, 307, 373, 375, 379; 6–8, 14, 96, 118f, 120f; and gas, 14; and with hepatocellular carcinoma, 647; in Hirschsprung’s disease, 388; vigorous, pancreas, 434, 445; with ulcerative colitis, 121–2 342t achlorhydria, 57t, 217, 245t, 451 abetalipoproteinemia, 194, 201t acid perfusion test, 98, 106t abscesses: amebic, 392; anorectal, 397, 399, acid suppressants, 145 406–7; appendiceal, 320t; colonic, 391; acidosis: children, 687t, 689, 698, 715, 727t, crypt, 285, 331, 332f; diverticuler, 253; 729; cirrhosis, 571, 591; ischemia, 253, and diverticulitis, 373; eosinophilic, 114; 266; liver transplantation, 641; pancreatitis, horseshoe, 406; liver, 474; lung, 113; 433t; ulcerative colitis, 335 pancreatic, 434; pararectal, 316t; perianal, acids (chemicals), 115 344t acinar cells, 56, 418–19, 422 absorption: of carbohydrates, 194–9, 227–8; acquired immunodeficiency syndrome. see in colon, 360, 362–4; of electrolytes, AIDS 185–92, 333; of fat, 192–4; of glucose, acrodermatitis enteropathica, 205t 194f; principles of, 178; of protein, actinomycosis, 149 199–202; of vitamins and minerals, acute abdomen, 24–7 178–83; of water, 183–5, 360 acute mesenteric ischemia, 252–4 acanthosis, glycogen, esophageal, 126t acyclovir, 294t, 301, 653 acanthosis nigricans, 126 acyclovir treatment, 114 ACE inhibitors.
    [Show full text]
  • The Physiology and Pathophysiology of Pancreatic Ductal Secretion the Background for Clinicians
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by SZTE Publicatio Repozitórium - SZTE - Repository of Publications REVIEW The Physiology and Pathophysiology of Pancreatic Ductal Secretion The Background for Clinicians Petra Pallagi, PhD,* Péter Hegyi, MD, PhD, DSc,*† and Zoltán Rakonczay, Jr, MD, PhD, DSc* and basolateral transporters involved in the secretory process. Abstract: The human exocrine pancreas consists of 2 main cell types: In all cases, the physiological function of this alkaline fluid is acinar and ductal cells. These exocrine cells interact closely to contribute to neutralize the acidic content secreted by acinar cells, to pro- to the secretion of pancreatic juice. The most important ion in terms of − vide an optimal pH for digestive enzymes, to flush down diges- the pancreatic ductal secretion is HCO3. In fact, duct cells produce an alka- − tive enzyme into the duodenum, and also to neutralize the line fluid that may contain up to 140 mM NaHCO3, which is essential for 7 − gastric acid entering the duodenum. Importantly, HCO3 has normal digestion. This article provides an overview of the basics of pancre- a crucial biochemical role in the physiological pH buffering atic ductal physiology and pathophysiology. In the first part of the article, system and is a chaotropic agent that prevents the denaturing we discuss the ductal electrolyte and fluid transporters and their regulation. of proteins such as digestive enzymes and mucins so it facili- The central role of cystic fibrosis transmembrane conductance regulator 4,8 − tates their solubilization in biological fluid. (CFTR) is highlighted, which is much more than just a Cl channel.
    [Show full text]
  • The Endodermal Origin of Digestive and Respiratory Tract APUD Cells Histopathologic Evidence and a Review of the Literature Gurdip S
    The Endodermal Origin of Digestive and Respiratory Tract APUD Cells Histopathologic Evidence and a Review of the Literature Gurdip S. Sidhu, MD Twenty-seven small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous and small cell and/or anaplastic carcinoid-type histologic features were studied by light and electron microscopy. It was shown that the small cells have morphologic characteristics of APUD cells. Also presented are the histologic features of a carcinoma of the lung with large cell undifferentiated carci- noma, adenocarcinoma, squamous cell carcinoma, and giant cell carcinoma areas in the primary site and in several metastatic foci. Two of the renal metastases showed small cell carcinoma. The combined tumors and the numerous other similar neoplasms described in the literature and reviewed here suggest an endodermal origin for diges- tive and respiratory tract APUD cells based on the hypothesis that cancer is a clonal proliferation, and mucous and squamous cell differentiation is an endodermal rather than neural crest characteristic. The ultrastructural features of tumors of cells of known neural crest origin, including a medullary carcinoma of the thyroid, three carotid body tumors, a pheochromocytoma, and two cutaneous melanomas were compared with those of other APUD cell tumors including small cell carcinomas of the lung, two bronchial carcinoids, a carcinoid of the appendix, and a carcinoid of the kidney. Cells of the latter group sometimes possessed cytoplasmic tonofibrils, round compact masses of cytoplasmic microfilaments, and ductal lumina. These features were lacking in the former group and may signify a different embryologic origin. The histologic, histo- pathologic, and embryologic evidence regarding the origin of digestive and respiratory tract APUD cells is reviewed, showing that the former are, and the latter probably are, of endodermal and not neuroectodermal origin.
    [Show full text]