Index Acelchotine 43,45, 4 Acetylcholinesterase, 45 Acetyl CoA, 4 ‘Acinar ells 123 Actomegaly, 36 Ation potential cf cann apocyes, 63,64 of neuron, 31,98 Addison disease (see Primary adrenal insufficiency) Adenocarcinoma description of, 22 of large intestine, 115, 115. fling. 132 renal, 14 Adenolimontyss ‘anacomy of 147,148 ‘hormonal secretions, 147-148. Adenosine triphosphate, 4 ‘Adipocytes, 27-28 ‘Adreal gland Saxony of, 158-159 linia donde of, 159, 161, 166-165 hormones, 159, 160 byperlasta of 164-165. byporlara of 164-165 ilhistration of, 164-165 smedulhe blood supply, 162 nines synthesis and metabolism, 163 lineal donde of, 162-163 Sescription of, 161 ilhsration of 166 Adrenocortical hormemnes, 159, 160 ‘Adrenoleukodystophy, 5-5 Adult polyeystic kidney disease, 145 Airway resistance, 130 ‘Albi, 192 ‘Alecholiccirthoss, 127 Aldosterone, 138, 158 Alkaline phosphatace, 33-34 Alport syrome, 28, 140 Alveolar pores, 31 ‘Alsheimer' disease, 204 Amenontrea, 169, 1710 ‘Amino ack oxidase, § ‘yAminaburyie ack, 54 ‘Amyloid light chain protein, 29 ‘Amloidoni, 29 References in italics indicate figures; those followed by denote tables Amnyocrophic lateral sclerosis, 56 ‘Anal canal, 111, 112, 113 ‘Anaphylactic reactions, 84 “Androgen-binding procein, 178, 181 SacAndrostanediol, 180 Androstenedione, 180 ‘Anemia hemolytic, 88 irom deficiency, 87 Angiotensin I, 38. Angiotensin li, 38 Ankyrin, 9 “Anterior vermis syndrome, 208 ‘Anterograde transport, SL ‘Antidiuretic hormone, 138, 148 Antimyein A, 4 ‘qy-Antteypsi, 117 Apocrine sweat glands, 191 ‘Apoptosis, 11,17 Arterioles, 69 Arteriovenous anastomoses, 69 ‘Aspergillus fomiganes, 132 Astrocytes, 52, 55 ‘Astrocytoms, 56-57, 61 Atherosclerors, 73, Aral natriuretic peptide, 65 Aurioventticular node, 67 ‘Axon ‘myelinated, 60 unmyelinated, 69 Asonal transport, 51 Bare body, 1 ‘sal lamina, 22 Basket cells 205 Basophils, 82 Biguanides, 127 ‘Bile canaliculus, 120 Bile duct, 18 Biliary crtosis, 119 Billroth cords, 101 Blood ‘composition of hemoglobin, 79 plasina, 78 red blood cell, 78-79 white blood cell (see White blood cells) dlsorders of, 87-92 flow of, 93-99‘Blood —Continued hemostasis, 84-86, 85 hypersensitivity reactions, 83-84 ‘Blood-air baie, 131, 133, Blood-brain barrier, $5, 57 Blood-CSF barter, 55, Blood! gas exchange, 79-81, 89 Blood group antigens, 78 Bloc thymus barrier, 95,97 B lymphocytes, 82-83 Bamemory cells, 83 Bone ‘ood vessels and nerves, 34 aap sod, compart herven, ST ‘osteoblasts, 33-34 ‘osteocytes, 4 ‘ostcoprogenitor, 33 clinical disorders of, 36-37 38 composition of 33 description of, 33, hhormonal influences, 35-36 ‘osteogenesis of, 34-35 repair of, 35. resorption of, 34 spongy, 36 ‘Bowel (see Large incestine; Small intestine) ‘Bowman’ capsule, 136 Breast snanomy of, 172, 176 fbroadenoma of, 176 {nfltrating duct carcinoma of, 177 Bronchogentc carcinoma, 132 Brush cells, 130 Bullous pemphigoid 22 Bundle tranches, 67 Bundle of His, 67 Bure cells, 89 Calettonin, 35 Calcium homeostasis, 156, 157 (Cancer (see Carcinoma) (Candida albicans, 152 Capillaries, 69, 76 Carbohydrates, digestion of, 106 ‘Garkon monoxide poisoning, 81 Carcinoma bronchogenic, 132 cervical, 171.175 ‘medullary, 135 papillary, 155 prostate, 189 small eel, 132 squamous cell ‘of cervix, 171 ‘of lung, 132, 134-135 Candiac muscle, 46, 47,50 Cardiac myocytes, ‘action potential of, 63, 6 anatomy of, 63 contraction of, 64, 65, Cartilage bbone and, comparison between, 37t characteristics of, 31-32 (Catecholarines, 54, 163, Celiac disease, 107, 109 Cell cycle factors that control, 10-11 phases of, 10t Call inclusions hhemosiderin, 1-12 lipofuscin, 11 Cell membrane sdescription of, 7 lipid component of, 7-8 protein component of clinical disorders, 9-10 ‘composition of, 8 ‘methods fr studying, 9 receptor proteins, 8 Calls (ee alo specific ype of cell) apoptosis, 11,17 one ‘osceoblasts, 33-34 osteocytes, 4 ‘osteoprogenitor, 33 ‘connective issue adipocytes, 27-28 fixed, 26-27 mast, 27 resident, 26-27 transient, 28 ‘eytoplasin (see Cytoplasin) red Hood, 78-79 transformation to cancer cell 18 white blood (see White blood cells) Central nervous system degeneration of, 56 regeneration of, 56 Centromeres, 1 Cerebellar cortex anatomy of, 207 clinical disorders of, 208 ‘eytonrchitecture of, 205, 205t slomerulus, 205-207, 206 Cerebral cortex in Alsheimer’s disease, 204 anatomy of, 203 ‘ytoarchitectute of, 202, 2021 ‘organization of, 202, Cervical intraepithelial neoplasa 174 anatoany of, 170-171 carcinoma of, 171, 175 ‘vagina and, junction berween. 17422 Index Dipalmitoylphosphatidylcholine, 131 Distal convoluted tubule, 136 Dopamine, $4¢ Duchenne muscular dystrophy, 45 Dynamine, 6 Dysplastic nevi, 192 Ear membranous labyrinch anatomy of, 193,194 ochleat duct 193-195, 194-195 description of, 193 saceule, 193, 194 semicicalar ducts, 193, 194 uricle 193, 194 ‘ympane membrane of, 193 Eccrine sweat glands, 190 Ectopic pacemakers, 67 Ectopic pregnancy, 167 Eniere-Danlos syndrome, 28 Elastic artery 69 Elastic fers, 26,30 Endocandiu, 63 Endocervical canal, 171 Endacrine amyloid, 29 Endocrine cells, 130 Endometriosis 169 Endometrum, of wens, 168, 173 Endothelin, 1 Endothelium, 70 En plac potential, 45 Enteroendocrine ells, 103, 107, 108 Eosinophils, 81,93 Ependymal cel, 55 Epicardium, 65 Epideris, 190 Epidermolsshulless, 192 Epinephrine, 54,162 Epirhyscal plate 35,37, pitti ell ‘apical region of, 19 bal region of, 20,22 lateral region of 19-20 polarity of, 1-21, 21 Eptehlium clasifcation of, 19, 20e lineal disorders of, 22 description of 19 EnythroblastosisFerals, 79 Erythrocytes (28 Red Hood eels) Evchromatn, | Excitatory postsynaptic potential, 52 Exocrine pancreay 123,128 Eraglomerulr mesangial eal 138 ye “lary body of, 200 clinical disocders of, 199 ‘comes of, 196, 200-201 limbus of, 196 retina of anatomy of, 196, 197, 200 visual transduction, 196-197 Fallopian tubes (see Uterine tubes) Familial adenomatous polyposis coli, 111, 114 Familial hypercholesterolemia, 9 Fasciculations, 45 Fatty acids, 106 Fe-antibody receptors, 27 Feley syndrome, 102 Female reproductive system ‘cervix, 170-171 ‘corpus lutcum, 167 ‘mammary gland, 172, 176 ovary, 167, 168¢ uterine tubes, 167 ters ‘endometrium, 168, 173, menstrual cycle, 168-169 myomersium, 169 vagina, 171-172 Fenestrated capillary, 69, 76 Ferritin, It Ferroheme, 106 Fertilization, of ovum, 167 Fibrllin, 28 Fibcoadenoma, of breast, 176 Fibeoblasts, 26 Fibrocytes, 26 Fibeonectin, 25 Filamentous actin, 6 Filtration barrier, of urinary system, 137-138 First-degree heart block, 67 Follicle-stimulating hormone, 18] Follicular cells, 150, 151 Foves, 196 Free cells, 28, Gall blader, 122 Gandy-Gamina nodules, 102 Gap junetion, 20, 21, 24 Garcnerela vaginalis, 172 Gardner syndrome, 113 Gastric glands, 103, 104 Gastric-inhibitory pepride, 107, Gastric ulcers, 105 Gaucher’ disease, 6 Germ cell neoplasms, 185 Glial fibril acc protein, 7¢ Glomerular filtration rate, 139-140, 140 Glucagon, 103, 124 Glucagon ‘like peptie-t, 107Dipalmitoylphowphariylchatine, 131 Darl convoluted tubule, 136 ‘Dopamine, 54¢ Duchenne muscular dystrophy, 46 Dynamine, 6 Dyin Dysmenorthea, 169 Dysplastie nevi, 192 Ex ‘membranous labyrinth anatomy of, 193, 194 cheat dct, 193-195, 194-195 description of, 193 saceule, 193, 194 semicrcalar duct, 193,194 crcl, 193,194 tympanic membrane of 193 Eccrine sweat glands, 190 Ectopic pacemaker 67 Ectopic pregnancy, 167 Ehlers-Danlos syndrome, 28 Ele artery, 6? Elastic fibers, 26, 30 Endocardium, 63 Endocervial cana, 171 Endocrine amyloid, 29 Endocrine cells, 130 Endometions, 169 Endometrium, of uterus, 168, 173 Enchehalin, | Endetheliu, 70 End plate potential, 45 Enretoendoctin cells, 103,107,108 Enninophls 8198 Ependymal cells, 55 Epicardium, 65 Epidermis, 190 Epidermolysis bullosa, 192 Epinephrine, 54t, 163 Epinhysal plate, 35,37 Eputbelal cel apical region of, 19. ‘basal region of, 20, 22 lateral region of, 19-20, polarity of, 19-21, 21 Epithelium lasiation of, 19, 20¢ clinical disorders of, 22 description of, 19 Erythroblastosis fetalis, 79 Erythrocytes (see Red blood cells) Enchromatin 1 Excitatory postynaptie potential, 52 Exocrine Pncrean 123,128 Peotone ‘mesangial cells, 138 re ciliary body of, 200 clinical disorders of, 199 ‘comea of, 196, 200-201 limbus of 196 retina of ‘anatomy of, 196, 197%, 200 diagrammatic representation of, 198 reds, 201 visual transduction, 196-197 Fallopian tubes (see Urerine tubes) Familial adenomatous polyposis coli, 111, 114 Familial hypercholesterolemia, 9 Fasciculations, 45, Fatty acids, 106 Fe antibody receptors, 27 Felty syndrome, 102 Female reproductive system ‘cervix, 170-171 ‘conpus luteum, 167 ‘mammary gland, 172, 176 ‘ovary, 167, 168t ‘uterine tubes, 167 ters ‘endometrium, 168, 173. menstrual cycle, 168-169 myometrium, 169 vagina, 171-172 Fenestrated capillary, 69, 76 Feritin, 11 Ferroheme, 106 Fertilization, of ovum, 167 Fibellin, 28 Fibroudenoma, of breast, 176 Fibroblasts, 26 Fibeocytes, 26 Fibeonectin, 25 Filamentous actin, 6 Filtration barrier, of urinary system, 137-138 First-degree heart block, 67 Follicle-stimulating hormone, 181 Follicular cells, 150, 151 Foves, 196 Free cells, 28 Gall bladder, 122 Gandy-Gamina nodules, 102 Glial fibsilar acidic protein, 7¢ Glomerular filtration rate, 139-140, 140 Glucagon, 103, 124 ‘Glucagon: like peptide-1, 107Iron deficiency anemia, 87 Islet of Langerhans, 123, 124, 129 Isodesmasine, 26 JG complex, 138 Juxtaglomerular apparatus, 144 Keratinocytes, 199, 191¢ Kericterus, 79 Kidney adenocarcinoma, 141 sorter, 142 isowders of, 140-141, 145-146 ‘medulla, 142 tubules, 136, 137, 139 Kinesin, 6 Kineachores, | Kinocilium, 193 Krabbe’ disease, 6 Kupfer cells, 117, 120 Lacs cell 138 Lactate dehydrogenase, 68, 6% Lrerowe intolerance, 11D Laminin, 7825 Laplace law, 3 Large intestine canal canal, 111, 112, 113 linea deeds of, 111, 113-116 flands, 111 ‘mucosa of, LIL repairof 11 Lend poisoning. 88 Lecithin-cholesterol acyl transferase, 116 Leder heneitary optic neuropathy, 4 Lsiomyema, 169 Lepein, 28 Leukernia chron lymphocytic, 97 chron myelo hairy eal 92 Letkotriene Cy 27 Usukotrene Dy 27 Leydig cells, 179-160, 181, 184 Lipoeytes, 117 Lipofisein, LE Lpopoeacharides,27 poet, 1167 Cishesis of, 121 Slaw ivr lobule, 117-118, 118, clinical disorders of, 119 hepatocyte T6117, 119%, 120 Koper ells 117,125, tipoeyter 117 liver acinus, 118, 118, 119 Iyemph production, 118-119 repair of, 9 Live acinus, 118,118, 19¢ Leal eet neon, 203 Long bones, growth of, 35, Loop of Henle, 136, 139¢ Lenedensitylipoproein, 116, L17¢ Lung (see also Respiratory system) cancer of 132 infections of, 182 Luteinizing hormone, 181 Lah Mow of, 98 liver production of, 118-119 Lymph node, 98-109, 100 Lymphocytes Ber illustration of, 94 T (se T lymphocytes) Lysosomal storage dicwses, 6 ysosomes 45 | Macrophages, 26-27 Macul, 196 Macula adherens, 20, 21 | Macula densa ces, 138 Male reproductive system clini disorders of, 182 hormonal control of, 181 Leylg cells, 179-180, 181, 184 prostate gland anatomy of, 182, 187, benign hyperplasia of, 188 carcinoma of, 189) seminiferous tubules, 178, 183 sperm, 179, 160 spermiogenesis, 178-179, 179 lymphoma of, 182 teratocarcinoma of, 186 Malignant melanoma, 192 Mammary gland anatomy of, 172, 176 fibeoadenoma of, 175 infiltrating duct carcinoma of, 177 Mammoctophs, 148¢ Marfan eyndrome, 28 Mast cells, 27 Maturity onset diabetes of the young, 126-127 MeArdle disease, 12 Meells, 107 Medullary carcinoma, 155 Medulloblastoma, 208, Meissner’s corpuscles, 192 Melanocyte-stimulating hormone, 147 ‘Membranous labyrinth, of eat, 193-195, 194Iron deficiency anemia, 87 Islet of Langerhans, 123, 124, 129 Isoxesmosine, 26 JGcomplex, 138 JJoxtaglomerular apparatus, 144 Kaposi sarcoma, 77, Kartagener syuirome, 22 Keloid formation, 29 Keratan sulfae, 25 Keratinocytes, 190, 19Lt Kericterus, 79 Kidney adenocarcinoma, 141 cortex, 142 disorders of, 140-141, 145-146 medulla, 142 tubules, 136, 137, 139¢ Kinesin, 6 Kinetochores, 1 Kinocilium, 193 Krabbe disease, 6t Kupfer cells, 117, 120 Lacis cells, 138 Lactate dehydrogenase, 68, 69t Lactone intolerance, 110 Laminin, 7,25 Laplace ia, 131 Large intestine anal canal, 111, 112, 113e clinical dionders of, 111, 113-114 ‘lands, 111 truco of 111 repair of, LLL Lead poisoning, 88 Lecithin-cholescerol acyl transferase, 116 Leder’ hereditary optic neuropathy, 4 LLeiomyoma, 169 Leptin, 28, Leukemia hairy cell, 92 Leukotriene Cy, 27 Leukowtiene Dy, 27 Leydig cells, 179-180, 181, 184 pots Lipopolysaccharides, 27 Lipoproteins, 116,117 Liver Cithosisef, 121 classic liver lobule, 177-118, 18 clinical disorders of, 19 hepatocytes, 116-117, 119,120 Kupfer cells, 117, 120 lipocytes, 117 liver acinus, 118, 118, 119 Iymmph production, 118-119 repair of, 19 Liver acinus, 18, 118, 119¢ Local circuit neurons, 203¢ Long bones, growth of, 35 Loop of Henle, 136, 139 Low-density lipoprotein, 116, 117t Lang (se also Respracory system) cancer of, 132 infections of, 132 Luteinizing hormone, 181 Bymah flow of, 98 liver production of, 118-119 Lymph node, 98-100, 100 recs B, 82-83 illustration of, 94 T (see T lymphocytes) Male reproductive system, clinical disorders of, 182 hormonal contro of, 181 Leydig ells, 179-180, 181, 184 prostate gland anatomy of, 182, 187 benign hyperplasia of, 188, carcinoma of, 189 seminiferous tubules, 178, 183 sperm, 179, 180 spermiogenesis, 178-179, 179 estes Tymphoma of, 182 teratocacinoma of, 186 Malignant melanoma, 192 Mammary gland ‘anatomy of, 172, 176 flomdenoma of, 176 pqiteig cn of 77 , 8c Marian syndrome, 28 Mast ells, 27 Maturity onset diabetes ofthe young, 126-127 McArdle disewe, 12 Meclls 107 Medllary carcinoma, 155 Medulloblastoma, 208 Meisner corpuscles, 192 Melanocyte-stimulating hormone, 147 Membranous abyrinch, of et 193-195, 194Menorthagia, 169 Menstrual cycle disorders, 169 hhormonal control of, 170 phases of, 168-169 Merkel endings, 192 Mesangium, 136 Metarterioles, 69 Metrorthagia, 169 Microglia, 35 Microtubules, 6 Microw, 19, 23, Mifepristone, 167 Mitochondria ‘clinical disorders of, 4 components and contents of, 4, 5t furiction of, 4 ilustration of, 15 Mitosis, 10 Monocytes, 82 Mossy fibers, 205, 206, Motor neuron disease, 56 Motor unit, 45 ‘Malletian inhibitory factor, 178 Multiple sleross, 56, 62 ‘Muscarinic acetylcholine receptor, 68 Muscle ‘cara, 46, 47,50, skeletal characteristics of, 47¢ circulation, 71t clinical disorders of, 46 ‘contraction of, 43,44 ‘eross-strations, 41-42 denervation of 45 fiber types, 41. 41¢ Alustration of, 48 innervation of, 45, ‘myofilaments, 42, 42-43 neuromuscular junction of, 43-44, 49 repai of, 45, sireich receptors, 45-46 smooth, 46-47, 47 Muscle fibers skeletal, 41, 4 smooth, 46-47 Muscular artery, 69, 72, Myasthenia gravis, 46 ‘Myelinated axon, 60, “Myocardial endocrine cells, 65 Myocardial infarction ‘enzyme levels in, 68, 69¢ illustration of, 74 Myocardium, 63, 64 Myoclonic epileptic ragaed re fber disease, 4 ‘action potential of, 63, 6 anatomy of 63 emtraction of, 64. 65 Putkinje 46,65, 67,75 Myoflamens of cet msc, 42,4248 Myometrium, 169 Myosin, 42-43 Nabothian cysts, 171 Natural killer cells, 83 Nephrons, 136, 143 Nephiroscleross, 146 Nervous system (see Central nervous system; Periph- eral nervous system) Neuroblascoma, 163-164, 166 Neuroglia cells, 52, 5 Newohrpophiy 148 149 ‘action potential, 51,53 ‘axonal transport, 51 ‘of cerebellar contex, 205, 206-207 (of cerebral cortex, 202, 203¢ ts of 51, 52¢ description of, 51 local cireuit, 203¢ ‘neurotransmitter, 52, 54¢-55t Node of Ranvier, 52, 59 ‘pyramidal, 202 stellate projection, 202, 203t synapse, 51-52, 59 ‘Neuropeptides, 55¢ Neurophysin, 148 Neutrophils, 81, 93 Nicotinic aceryicholine receptor, 45, ‘Niemann-Pick disease, 6t Night blindness, 199 Nitric oxide description of, 70 ‘smooth muscle cell effects, 70 Node of Ranvier, 52,59 Norepinephrine, 54, 68, 162 Nuclear envelope, 1,13, ‘Nuclear lamina, 1 Nuclear pore complex, 1,2¢, 13 Nucleokis,2 Nucleosome, 1, 14 Nucleus, 15 Nyctalopia (se Night blindness) Oligodendrocytes, 52, 38 Oligomycin, 4 Opioid peprides, 55¢ Oran ef ont ‘Corti, 193,195 Ossification, 4-35, Omeoblasts, 33-34 Osteocalcin, 33 Osteoelas, 39 Onteoeytes, 34Qnecgeness, Osteogenesis imperfecta, 28 Ostecid, 33 Osteomalacia, 36 Onteoporesis, 36 Ostecprogenicor cells 33 ‘Orolithie membrane, 193 Ovary, 167, 168e Oxyhemoglcbin, 79 Onyphil cells, 156 Orytocin, 148 Pocinian corpuscles, 192 Paget's disease, 36 Panes ‘exocrine, 123, 128 insulin ceptor, 123, 125 inlerof Langerhans, 123,124, 129 Pancreatitis, 128 Paneth cells, 107, 108, Papillary eacinoma, 155 Popilledema, 199 Pop smear, 71, 1714, 174 Parafollicular cells, 152 Parasympathetic sytem, 67-68 Parathyroid gland, 156,157 Parathyroid hormone, 35, 156 Parietal cells, 103,104 Parkinson discase, 56 Pars deals, 147, 148 Pars intermedia, 147 Pars uberalis, 147 Pepsin, 103 Pepsinogen, 103 Peptidyl sine hydroxylase, 26 Pepridyl proline hydroxylase, 26 Perikaryon, 52¢ Perinuclear cistema, 1 Peripheral nervous system ‘degeneration of, 35-56 regeneration of 56 proliferatoractivated revepeor-y, 127 Peroeisomes, 5-6 Pheochromocytoma 162-163, 165 Phosphatidlinositl 3-kinase, 123 Phospholipase C, 8 Phospholipids description of, 3 types of, 7-8 Pieucytes, 148 Plasina, 78 Plasma cells, 82-83 Platelets, 84 Pewenoets cari, 132 Pheumocytes, 131, 134 Podocytes, 136, 143 Poiseulle law, 30 Polyribexome, 2-3 Pompe's disease, 6t Pores of Kohn (See Alveolar pores) Portal vein, 118 Posterior vermis syndrome, 208 Postmenopausal bleeding, 170 Prepbertl bleeding, 170 Primary adrenal insuffciency, 161, 1618 Primary amenorchea, 169 Primary amyloidosis, 29 Primary biliary cirthoss, 119 Primary hyperaldosteronism, 159, 1614 Primary hyperparathyrovdism, 156 Primary hypoparathyroidism, 156 Primary hypothyroidism, 152, 153 Primary sclerosing cholangitis, 119 Progresaive bulbar palsy, 56 Progressive muscular atrophy, 56 Prolactin, 172 Prostacyclin, 70 Prostate gland anatomy of, 182, 187 benign hyperplasia of, 188 carcinoma of, 169 Prostate-speciic antigen, 182 Protein, 106 Procein-secreting cell, 16 Proceoglycans, 25, 30 Pseudohypoparathyroidism, 156 Pseudostratifed columnar epithelium, 20¢ Purkinje cells, 205, 206 Purkinje myocytes, 45, 5, 67,75 Eyam neurons, 202 2 53 sine Anger protein, 11 Rapidly progressive glomenslonepheitis, 146 Reactive hyperemia, 70 Reactive systemic amyloidosis, 29 Receptorsmedited enocytns, 9 Red blood cell membranes description of 9 proven component of, 9, 9 Rea blood calls, 78-79, Red ber 41, 41¢ Sa-Reductae 2 deficiency 182 Reed-Stemberg cells, 92 Releasing hormones, 147-148 Renal adenocarcinoma, 14 Renal capsule, 136 Rena glomerulus, 136 Renal tubules, 136, 137, 139¢ Reproductive system (se Female reprochictve sp tem Mae eproductve system) Respiratory butt oxidase, 81 Respiratory distress syndrome, 131-132 Respiratory eptheliam, 130 Respiratory system (ee lo Lung) alveok of, 13‘blood-air barrier, 131, 133 bronchi of, 130-131 60,000 4) such as Nucleus + cytoplasm Active transport ‘nucleoplasmin, steroid Requires ATP hydrolysis receptors, DNA and RNA Requites a signal sequence of 4-8 polymerases, gene regula. ‘amino acids for recognition by the tory proteins, RNAprocess- ‘nuclear pore complex ing prot [ATP = adenosine wiphosphate: MRNA = messenger RNA FRNA = ribosomal RNA; TRNA = Vansfor RNA. polymerase Band €, which catalyze DNA repair, and DNA polymerase 7, which catalyzes mitochondrial DNA replication. D. The nucleolus consists of portions of five pairs of chromosomes (Le., 13, 14, 15, 21, ‘and 22) that contain genes that code for ribosomal RNA (rRNA). In humans, RNA polymerase I catalyzes the formation of fRNA. Other RNA polymerases exist within the cell; namely RNA polymerase II, which catalyzes the formation of messenger RNA (mRNA), and RNA polymerase ITT, which catalyzes the formation of transfer RNA (tRNA). By electron microscopy, three regions of the nucleolus ean be distin- quished. 4. The fibrillar center is palestaining and contains transcriptionally inactive DNA. 2. The dense fibrillar component contains RNA in the process of being synthesized. 3. The granular component contains #RNA bound to ribosomal proteins beginning ‘to mature into ribosomes. I. CYTOPLASM contains enzymes for glycolysis, fatty acid synthesis (Le.,farty acid syne thase), three reactions of the urea cycle (using argininosuccinate synthetase, argininosuc- inate lyase, and arginase), glycogen synthesis and degradation, and protein synthesis, as well as intermediates of metabolism and many cofactors. Ill, CYTOPLASMIC STRUCTURES A. Ribosomes: 1. Ribosomes consist of 40S (small) and 60S (large) subunits containing FRNA and various proteins (Table 1-2). 2, ‘They are the sites where translation of mRNA into en amino acid sequence (i.e protein synthesis) occurs 3. Ribosomes may cluster along a strand of mRNA to form a polyribosome (or !Table 1-2 Ribosomal Subunits ‘Number Subunit RNAType of Proteins Functions. 408 185 =33 Has binding sites for mRNA and {RNA Binds to mRNA and finds the start codon AUG 60s 58,585,285 249 Binds to the 40S subunit after 40S subunit finds the start codon AUG Has peptidyl transferase activity {FRNA = ribosomal RNA; mRNA = mossongor RNA: (RNA = anstor RNA. polysome) that is involved in the synthesis of cytoplasmic proteins (c.g. actin, hemoglobulin), 4. They may be directed to the endoplasmic reticulum to form FER if the nascent pro- {cin contains a hydrophobic signal sequence at its amino terminal end, which is cleaved in the rER lumen by signal peptidase. B. rER. This membranous organelle contains ribosomes attached to its cytoplasmic sur- face by the binding of ribophorin I and II to the ribosomal 60S subunit. . Ie isthe site of synthesis of secretory proteins (eg. insulin), cell membrane pro teins (e.g. receptors), and Iysosomal enzymes. 2. It's the site of co-translational modification of proteins: a. Nelinked glycosylation (addition of sugars to asparagine begins in the rER and is completed in the Golgi complex) 1b. Hydroxylation of proline and lysine during collagen synthesis ©. Cleavage of the signal sequence d._ Folding of the nascent protein into three-dimensional configuration Association of protein subunits into multimeric complex G. Smooth endoplasmic reticulum (sER) isa membranous organelle that contains no ti bosomes. Iris involved in: 4. Synthesis of membrane phospholipids (phosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylthanolamine), cholesterol, and ceramide 2. Synthesis of steroid hormones in testes, ovary, adrenal cortex, and placenta 3. Drug detoxification using cytochrome Pysoy which isa family of heme proteins (alko called mixed-fanction oxidase system) that participates in hydroxylation of barbiturates, phenytoin, or benzopyrene (a carcinogen found in cigarette smoke), makes them more soluble in water, and allows excretion into the urine 8. Activation of cytochrome Pyjy by one agent enhances the detoxification of other agents, which has clinieat implications. b. In chronic alcoholics or newborns, large amounts of anesthesia agents are needed (which may be dangerous) because cytochrome Py has been acti- vated by detoxifying either alcohol or breakdown products of fetal hemeglob- ulin, respectively 4, Fatty acid elongation 5. Calcium fluxes associated with muscle contraction D. Golgi complexes are stacks of membranous cisternae with a cis-face (convex) that re-«ccives vesicles of newly synthesized proteins from the 1B and a trans-face (concave) that releases condensing vacuoles of posttranslationally moxified proteins. 1. Icis the ste of postteanslational modification of proteins, sich as: @. Completion of N-linked glycosylation that began in the rER 1b. O-linked glycosylation; that is, addition of sugars to serine by the enzyme gly- conyliransferase ©. Sulfation |. Phosphorylation (phosphorylation of mannose forming mannose-6-phos- phate occurs only in lysosomal enzymes) 2. Icis involved in protein sorting and packaging, J. Secretory proteins (e., insulin) are packaged into clathrin-coated vesicles. . Coll membrane proteins (ex. recepton) are packaged into nonelathrin + Lysosomal eneymes ae packaged ino clathrin-coated vesicles after phospho ‘ylation of mannose. 3. Icisinvolved in membrane recycling. E. Mitochondria 4. Function, Mitochondria are involved in the production of acetyl coenzyme A (CoA), the tricarboxylic acid cycle, fary acid B-enidation, amino acid oxidation, and oxidative phosphorylation [which causes the synthesis of adenosine triphos” phate (ATP) ciriven by electron transfer to oxygen}. Substrates are metabolized in the mitochondrial matrix to produce acetyl CoA, which is oxidized by the tricarboxylie acid eycle to cathon dioxide by The energy released by this oxidation is captured by reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH,). NADH and FADH) are further oxidized, producing hydrogen ions and elec trons. @. Theelectrons are cransferred along the electron transport chain, which is ac~ companied by the outward pumping of hydrogen ions into the intermembrane space (chemiosmotic theory) . The Fo subunit of ATP synthase forms a transmembrane hydrogen ion pore so thar hydrogen ions ean flow from the intermembrane space into the matrix, ‘where the F; subunit of ATP synthase catalyzesthe reaction ADP + P,—> ATP. 2. Components and contents are listed in Table 1-3. 3. Clinical considerations ‘@. Leder’s hereditary optic neuropathy is characterized by progressive optic nerve degeneration and is caused by a mitochondrial DNA mutation in the zene for subunit + of the NADH dehydrogenase complex. Mitochondrial diseases are maternally inherited and affect tissues that have a high requite- ‘ment for ATP (e.g., nerve, muscle). b. Myoclonic epileptic ragged red fiber disease is characterized by progressive myoclonus (muscle jerking), dementia, and hearing loss. Ie is caused by a mi- tochondrial DNA mutation in the gene for tRNA for lysine, ©. Cyanide, carbon monoxide, and antimyein A inhibit the electron transport ‘chain and thus block ATP synthesis, 4d. Oligomycin and venturicidin are antibiotics that bind to ATP synthase and thus block ATP synthesis, F._Lysosomes are membrane-bound cnganelles that contain lysosomal enzymes (also called acid hydrolase enzymes) including cathepsin Band L (proteases), nuclease, 5’-nucleoti-Col Biology 8 Table 13 ‘Components and Contents ‘Components Contents Outer membrane Porin (a transport protein that increases permeability to metabolic ‘sustrates) Intermembrane space Hydrogen ions, Inner membrane Electron transport chain (NADH dehydrogenase, succinate dehydrogenase, (folded into cristae) ubiquinoneeytechrome ¢ oxidoreductase, cytochrome oxidase) [ATP synthase (found on elementary particles) [ATP-ADP translocator (moves ADP into the matrix and ATP out of the matrix) Matrix compartment Tricarboxylc acid (TCA) oycle enzymes (except succinate dehydrogenase) Fatty ocd B-oxidation enzymes. Amino acid oxidation enzymes Pyruvate dehydrogenase comalex Carbamoyiphosprate syntnetase | Omithine tronscarbamoylase (par of urea eye) DDNA, mRNA, tRNA, °RNA Granules containing calcium and magnesium ions NADH ~ reduced nicotinamide adenine dinuclootide: mRNA — mossongor RNA; (RNA = ribosomal RNA; RNA = twonafer ANA: ATP séenosine trphosphete (ATP); ADP ~ adenosine diphosphate (ADP). dase, B-galactosidase, B-glucuronidase, glycosidase, aryl sulfacase, lipase, esterase, and acid phosphatase that function at pH 5. Most lysosomes function intracellularly; however, some eels (eg, neutrophils ostedclsts) release thei lysosomal contents extracellularly. 4. Golgi hydrolase vesicles bud from the Golgi complex and contain inactive acid hydrolase enzymes. a. Golgi hydrolase vesicles fuse with a fate endosome, which contains an H?~ ATPase in its membrane that produces a pH 5 environment, which activates the acid hydrolases. 1b. A late cndosome may fuse with # phagocytic vacuole forming a phagolyso- some, which degrades material phagocytosed by the cell. €. A late endoscme may fuse with an autophagic vacuole forming. an aue tophagolysosome, which degrades cell organelles. 2. Residual hodies contain undigestible material anc! may accumulate within a cell as lipofuscin pigment. 3. Clinical considerations. There are a number of genetic diseases that involve mu- tations of genes for various lysosomal enzymes (acidl hydrolases; Table 1-4). Peroxisomes are membrane-bound ongonelles. L. Contents of peroxisomes include: a. Amino atid oxidase arn! hydroxyacid oxidase, which produce hydrogen per- cide (H,0,) th. Contato nel caiicn pctidanes thant docemnpte biyopen percicide ts weit and oxygen (H,0, > HO + 3) ce. Fatty acid B-oxidation enzymes that ovine long-chain fey acide (> 20 ca toms) to shore-chain fatty acids, which are transfered to mitochonria for ‘complete oxidation 2. Clinical consideration. Adrenoleukodystrophy is a genetic disease that involvesTable 1-4 Lysosomal Storage Diseases ‘Major Accumulating Disease Enzyme involved Metabolite Huner's disease Liéuronidase Heparen sulfate Deramatan sulfate Sanfilippo A Heparan sulfemidase Heparen sulfate Hexosaminidase A GM, ganglioside Baucosidase Glucosyleeramide Sphingomyelinase ‘Sphingomyelin ‘1, 4.Giucosidase (acid maitase) Giyeogen Phosphotransferase Mucopolysaccharide Brgslactosidase Galactosylceramide ‘mutation of genes for various peroxisomal enzymes used in fatty acid oxidation that results in abnormal accumulation of lipid in the brain, spinal cord, and adrenal gland and leads to dementia and adrenal failure. IV, CYTOSKELETON A. Filamentous actin (F-actin) 2. Feactin comprises microfilaments (6-nm diameter) arranged in a helix of poly- merized globular monomers of actin (G-actin). 22. Iris in.a constant state of polymerization and depolymerization. 3. Feactin functions in exocytosis, endocytesis,eytokinesis, locomotion of eellsform- ing lamellipodia, and movement of cell membrane proteins. 4. Cytochalasin is toxic fungal alkaloid thar causes F-actin to depolymerize.. 5. Phalloidin is toxic substance derived from the Amanita mushroom that binds to F-actin, thereby inhibiting polymerication/depolymerization, B. Intermediate filaments (10-nm to 12-nm diameter) 1. These function as the cytoplasmic link between the extracellular matrix, eytor plasm, and nucleus. 22. Invermediace lamers demonstrate specificity (Table 1-5) for certain cell rypesftue mors, and therefore can be used as markers for pathologic analysis. C. Microtubules are 25-rnm- tosis occurs in hormone-depensent involution of cells during the menstrual cycle, em- Inryogenesis, toxin-induced injury (e.g. diphtheria), viral cell death (e.g, Councilman, bodies in yellow fever), and cell death via eytotoxie T cells or other immune cells. Apop- tosis does not elicit an inflammatory response. Vill, CELL INCLUSIONS ‘A. Lipofuscin isa yellow-brown “wear and tear” pigment found predominately in esid- tual bodies, which are the end point of lysosomal digestion, 1, It is composed of phospholipids complexed with proteins, suzesting that it is de- rived from the lysosomal digestion of cellular membranes. 2. Lipofuscin isa telltale sign of free radical damage and isfound prominently within hepatocytes, skeletal muscle cells, and nerve cells of elderly people or patients with severe malnutrition. BB. Hemosiderin is. golden brown hemoglobin-derived pigment consisting of iron. 1, Iron is absorbed mainly by surfa ported in che plasma by a procein as ferritin, which isa protein-iton complex. ‘Small amounts of ferritin normally eirculate i the plasma, making plasma ferritin ‘a good indicator of the adequacy of body iron stores.In iron deficiency, serum ferritin is less than 12 ja. b. In iron overload, serum ferritin approaches 5000 jig. (2) Abo during iron overload, intracellular ferritin undergoes lysosomal degradation, in which the feritin procein is degraced and the iron aggre- gates within the cell as hemosiderin in a condition called hemosiderosis. (2) Hemosiderosis can be observed in patients with increased absorption of dietary iron, impaired utilization of iron, hemolytic anemias, andi blood. transfusions. C. Glycogen is the storage form of glucose and is composed of glucose units linked by a 14 glycosidie bonds. Glycogen synthesis is catalyzed by glycogen synthase. Glycogen, degradation is catalyzed by glycogen phosphorylase. Liver hepatocytesand skeletal mus- cle cells contain the largese glycogen stores, bur the function of glycogen differs widely. 11, Liver glycogen functions in the maintenance of blood glucose levels. ‘a. Synthesis. Liver glycogen is synthesized (using glycogen synthase) during a high-carbohydrate meal due to hyperglycemia and an increase in the in- sulin:glucagon ratio. 1b. Degradation. Liver glycogen is degraced (using liver glycogen phosphorylase isoenzyme) during hypoglycemia (e.g. fasting), exercise, or other stressful situations due m a decrease in the insulin:glucagon ratio and the secretion of epinephrine from the adrenal medulla, which binds to a- and B-adrenergic receptors on the hepatocyte (2) Liverelycogen is degraded to glucose-6-phosphate, which is catalyzed to free glucose by the enzyme ghicose-6-phosphatase (2) Glucose-6-phosphatase is found only in the liver and kidney. ‘Skeletal muscle glycogen functions in the formation of ATP through glycolysis. Synthesis. Skeleral muscle glycogen ts synthesized (using glycogen synthase) during carbohydrate meal cue to hyperglycemia and an inerease in the lucagon ratio. 1b, Degradation. Skeletal muscle glycogen is degraded (using muscle glycogen phosphorylase isoenzyme) during exercise or stressful situations due to a de crease in ATP, calcium released during contraction, and secretion of epi nephrine from the adrenal medulla, which binds to @- and B-adrenengic re- ‘ceptors on the skelecal muscle cell. (A) Skcletal muscle glycogen is degraced to ghucose-6-phosphate, which en- ters glycolysis to produce ATP. (2) The absence of glucose-6-phosphatase enzyme in skeletal muscle pre- vents the degradation of glycogen to free ghicose 3. Glycogen storage diseases are genetic diseases that involve mutations in one of the enzymes of glycogen synthesis or degradation. a. Von Gierke disease (type 1 glycogenosis) results from a deficiency in the en- zyme glucoe-6-phorphatase, causing an enlarged liver and severe hypo- lycemia. 1b, McArdle disease (type V glycogenosis) results from a deficiency in the en- zyme muscle glycogen phosphorylase, causing exercise-induced muscle pain and cramps.