Actinic cheilitis, 1145b ADAMTS13, in thrombotic
Actinic keratosis, 1145–1146, 1145b, 1146f microangiopathies, 666
Active plaques, in multiple Adaptations, cellular, 33–69
Index sclerosis, 1270b–1271b of growth and differentiation, 57–61
Active transport, 9–10 atrophy, 59–60, 60f
Acute antibody-mediated hyperplasia, 59
Page number followed by t, f, rejection, 236, 236b, 238f hypertrophy, 35f, 57–59, 58f
or b indicates table, figure, or box, Acute arthritis, 1205, 1205b metaplasia as, 61, 61f
respectively. Acute axonal injury, 1219f Adaptive immunity, 85, 190, 190f
Acute biliary obstruction, 854b defects in, 242–245
Acute cellular rejection, 236b peptide display system of, 198–199
A Acute chest syndrome, in sickle cell Adaptor proteins, 19
AA, Arachidonic acid disease, 643–644 ADCC, Antibody-dependent cell-mediated
AAA, Abdominal aortic aneurysm Acute cholecystitis, 875 cytotoxicity
Abdominal aortic aneurysm (AAA), 506– morphology of, 875b Addison disease, 1123–1124, 1124b
507, 506f, 506b Acute coronary syndromes, 543 Adenocarcinoma, 269
Abdominal pain, in acute pancreatitis, 885 Acute disseminated encephalomyelitis, 1272 of bladder, 962
Aberrantly expressed cellular proteins, as Acute eczematous dermatitis, 1154– of cervix, 999f, 999b–1000b
tumor antigens, 310 1155, 1155b, 1156f of colon, 271f
Abetalipoproteinemia, 787 stages of development, 1155f colorectal, 813–817
ABO incompatibility, fetal hydrops due Acute fatty liver of pregnancy (AFLP), 865 clinical features of, 816–817, 817f, 817t
to, 463 morphology of, 865b epidemiology of, 814
Abscess(es), 94 Acute GVHD, 239, 240f morphology of, 816f, 816b
caused by anaerobes, 379, 379b Acute hemolytic reactions, 671 pathogenesis of, 813t, 814–816, 815f
subareolar, recurrent, 1040 Acute hemorrhagic leukoencephalitis or staging of, 818t
Acanthamoeba, 1311 Weston Hurst, 1272 esophageal, 762–763, 763f, 763b
Acantholysis, 1161b Acute hepatitis, 838f gastric, 774–776, 775f–776f, 775b–776b
Acanthosis, 1135t Acute illness, and malnutrition, 433 of lung, 716–717
nigricans, 330, 1143, 1143b Acute inflammation, 73, 75–96 of prostate, 977–982
in type 2 diabetes mellitus, 1105 features of, 73t clinical features of, 981–982
Accessory spleens (spleniculi), 631 inflammatory chemokines in, 90 ductal, 982
ACE, Angiotensin-converting enzyme vascular reactions in, 76b etiology and pathogenesis of, 978
Acellular amyloid deposits, 1091b–1092b Acute inflammatory dermatoses, 1153–1156 grading and staging of, 980–981, 981f, 981t–982t
Acetaldehyde, oxidation of ethanol to Acute kidney injury, 896 morphology of, 979f–980f, 979b–980b
produce, 419 Acute liver failure, 826–827, 837 Adenohypophysis, 1066f
Acetaminophen, toxicity of, 422–423, 423f Acute lung injury (ALI), 676–678, 677b Adenoid cystic carcinoma, 1056b–1058b
Acetylsalicylic acid, 423 Acute lymphoblastic leukemia/lymphoma of salivary glands, 750, 751f, 751b
Achalasia, 757–758 (ALLs), 594–597, 596f, 604b–605b Adenoma(s), 268
Achondrogenesis, 1176t morphology of, 596b gastric, 774, 774b
Achondroplasia, 1175, 1176t Acute myeloid leukemia (AML), 590, 617– lactational, 1042b
Acid hydrolases, 154 620, 619f, 627b nephrogenic, 957
Acid proteases, in inflammation, 83 major subtypes of, 618t, 619f pituitary, 1067–1072, 1069f–1070f
Acidophil bodies, 825, 825f morphology of, 618b pleomorphic, 269
Acinar cell carcinoma, 893–894 Acute necrotizing hemorrhagic renal papillary, 948, 948b
Acinic cell carcinoma, 752f encephalomyelitis, 1272 of thyroid, 271f
Acinus, 673–674, 679f Acute neuronal injury, 1242b Adenomatoid tumors
Acne vulgaris, 1165, 1166f Acute nonspecific lymphadenitis, 588–589 of fallopian tubes, 1016
Acoustic neuroma, 1237 Acute pericarditis, 577–578 paratesticular, 969
Acquired genetic alterations, indications for Acute plaque change, 502–504 Adenomatous polyposis coli (APC), tumor
analysis of, 181 Acute promyelocytic leukemia suppressor genes, 297, 298f
Acquired immunodeficiency syndrome (APML), 317, 318f Adenomyosis, 1004–1006, 1006b
(AIDS), 247–259 Acute radiation syndromes, 431 Adenosarcomas, of endometrium, 1013
acute retroviral syndrome, 253–254 Acute rejection, 236b Adenosis, of breast, 1042b
clinical features of, 255–259 Acute respiratory distress syndrome sclerosing, 1043b
epidemiology of, 247–248 (ARDS), 137, 676–678, 676t, 677f, 678b Adenosquamous carcinoma, 1056b–1058b
Kaposi sarcoma and, 256 Acute retroviral syndrome, 254 Adenovirus, and viral gastroenteritis, 795
lymphomas in, 257–258 Acute rheumatic fever, 210t ADH, Antidiuretic hormone
major abnormalities of immune function Acute T cell-mediated rejection, 236, 237f Adhesins, 346
in, 252t Acute tubular injury, 924–926, 926b Adhesion receptors, 24–25
morphology of, 259b clinical course of, 926 Adhesive glycoproteins, 24–25, 26f
opportunistic infections with, 255–256, 256t morphology of, 925f, 925b–926b Adipocytes, in energy balance, 445f
pathogenesis of, 248–253, 259b pathogenesis of, 924–925, 924f Adipokines, in insulin resistance, 1104–
peripheral neuropathy in, 1222 Acute viral hepatitis, 837b–838b 1105
transmission of, 247–248 Acute-phase proteins, 102 Adiponectin, in energy balance, 447
tumors in, 256–258 Acute-phase reactants, 706 Adipose tissue, in energy balance, 447
Acquired lactase deficiency, 786 Acute-phase response, in inflammation, 101 Adjuvants, in immune responses, 200
ACTH-producing pituitary AD, Alzheimer disease Adnexal components, of skin, 1134
microadenoma, 1115 Adamantinomatous Adnexal tumors, 1144–1145, 1145f
Actin microfilaments, 11–12 craniopharyngioma, 1074f, 1074b Adrenal carcinoma, 1126f
Actinic band keratopathy, 1311 Adrenal cortex, 1115–1126
Adrenal cortical adenoma, 1125f AION, Anterior ischemic optic neuropathy Alveolar walls, 674, 674f
Adrenal cortical cell lipid depletion, due to Air embolism, 132 Alveoli, 673–674, 677f
shock, 138b Air pollution, carcinoma and, 716 Alzheimer disease (AD), 1275–1280, 1278f–
Adrenal glands, 1114–1129 “Airway remodeling,” in asthma, 685f– 1279f
Adrenal hypoplasia congenita, 1124 686f, 686b clinical features of, 1280
Adrenal incidentaloma, 1126 Alagille syndrome, 856 molecular genetics and pathogenesis of, 1275–
Adrenal medulla, 1114–1115, 1126–1129 Albers-Schönberg disease, 1176–1177 1278
Adrenal myelolipomas, 1126 Albinism, 148 AMD, Age-related macular degeneration
Adrenal neuroblastoma, 478f Alcohol Amebocytes, 73
Adrenal pheochromocytoma, 1127 blood level, 418–419 Ameloblastoma, of oral cavity, 739
Adrenocortical adenomas, 1125b–1126b effects of, 418–420, 420b Amenorrhea, 435–436
Adrenocortical hyperfunction, 1115–1121 myopathies and, 1231 AML, Acute myeloid leukemia
in adrenogenital syndromes, 1120–1121 as teratogen, 456 Ammonia, lung diseases due to, 692t
in hypercortisolism (Cushing syndrome), 1115– Alcohol abuse, 418 Amnion nodosum, 455
1118 and cancer, 278 Amniotic bands, 454, 454f
Adrenocortical insufficiency, 1122– Alcohol consumption, pancreatitis and, 884 Amniotic fluid embolism, 132, 133f
1125, 1122t, 1124b Alcohol dehydrogenase, alcohol oxidation Amphetamines, abuse of, 425
primary, chronic (Addison disease), 1123–1124 by, 419 Amphiboles, 694
secondary, 1124–1125 Alcoholic cardiomyopathy, and chronic Amplicon length analysis, 182
Adrenocortical neoplasms, 1119–1120, 1125 alcoholism, 420 Amplification, local, 185
Adrenogenital syndromes, 1120– Alcoholic cerebellar degeneration, 1292f Amyloid
1121, 1121b–1122b Alcoholic chronic pancreatitis, 887f, 888 of aging, 263
Adrenoleukodystrophy, 1124, 1290 Alcoholic cirrhosis, 845f chemical nature of, 260
ADRs, Adverse drug reactions Alcoholic liver disease, 842–845, 844f, 846b deposition within islets, 1108b–1109b
“Adult” postductal coarctation, 541b morphology of, 843b–844b endocrine, 263
Adult red cell (HbA), 641 Alcoholic steatohepatitis, 843b–844b physical nature of, 260
Adult stem cells, 28 Alcoholism structure of, 260f
Adult T-cell leukemia/lymphoma acute, 419–420 Amyloid light chain (AL) protein, 260
(ATLL), 595t, 605–606, 607b chronic, 420, 433 Amyloid precursor protein (APP), 260
human T-cell leukemia virus type 1 and, 324 ALDH2*2, 419 β-amyloid (Ab) protein, 260
Advanced glycation end products Aldosterone suppression test, 1120 Amyloid-associated (AA) protein, 260
(AGEs), 1108 Aldosterone-producing adenomas, 1119b Amyloidosis, 259–264, 263f, 264b–265b
Adventitia, of blood vessels, 486 Alexander disease, 1243 cardiac, 574, 575f
Adverse drug reactions (ADRs), 420– ALI, Acute lung injury classification of, 260–264, 261t
423, 421f, 421t Alignment, in bioinformatics, 185 clinical features of, 264
of acetaminophen, 422–423, 423f Alimentary tract, in systemic sclerosis, 232b hemodialysis-associated, 262
of anticoagulants, 421 Alkaptonuria, 65 and light-chain cast nephropathy, 934
of aspirin, 423 Allergic bronchopulmonary localized, 262–263
of menopausal hormone therapy, 421–422 aspergillosis, 687 morphology of, 263b–264b
of oral contraceptives, 422 Allergic diseases, chronic inflammation due pathogenesis of, 260–264, 261f
Aerobic glycolysis, in cancer, 300 to, 96 perivascular, 663
Affected females, of fragile-X Allergic rhinitis, 739 plasma cell disorders associated with, 261–262
syndrome, 175 Allergies, development of, 208 primary, 261–262
Affinity maturation, in humoral Allogeneic hematopoietic stem cell properties of amyloid and, 259–260
immunity, 203 transplantation, 621 reactive systemic, 262
Aflatoxin, 449 Allogeneic MHC molecules, recognition secondary, 102
hepatocarcinogenesis and, 868–869 of, 235–236 vascular, 264
Aflatoxin B1, 322 Allograft vasculopathy, 580 Amyotrophic lateral sclerosis (ALS), 1287–
AFLP, Acute fatty liver of pregnancy Allografts, mechanisms of recognition and 1288, 1288f, 1288b
African Americans, 574, 641 rejection of, 234–240, 240b Anaerobic bacteria, 379–380
African trypanosomiasis, 392, 393b Allorecognition Anal canal, tumors of, 818, 818f
Agammaglobulinemia, X-linked direct pathway of, 234–235 Analgesics, and bladder cancer, 958
(Bruton), 243–244 indirect pathway of, 234–235 Anaphase lag, 165
Age ALLs, Acute lymphoblastic Anaphylatoxins, 86, 91, 206
atherosclerosis and, 494–495 leukemia/lymphoma Anaphylaxis, 91
and breast cancer, 1046 All-trans-retinoic acid, 437 systemic, 208
and cancer, 278–279 and congenital anomalies, 457 Anaplasia, 270–273
Agenesis, 455 Alpha-thalassemia/mental retardation Anaplastic astrocytomas, 1294b–1295b
Age-related macular degeneration syndrome, X-linked (ATRX), 1113 Anaplastic (undifferentiated)
(AMD), 1323–1324, 1324f Alport syndrome, 922, 922f, 922b carcinomas, 1090–1091, 1091b–1092b
AGEs, Advanced glycation end products ALPS, Autoimmune lymphoproliferative Anaplastic large-cell
Aging, and heart, 529, 529t syndrome lymphoma, 595t, 605, 606f, 607b
Agranulocytosis, 586–587, 587b ALS, Amyotrophic lateral sclerosis Anaplastic (malignant) meningioma, 1300b–
Agricultural exposures, occupational health Alternative pathway, 91 1301b
risks, 414–418 Alveolar damage, diffuse, due to Anaplastic oligodendrogliomas, 1296b
Agyria, 1247 shock, 138b Anaplastic tumors, 271f
AID, Antigen-induced cytosine deaminase Alveolar ducts, 673–674 ANAs, Antinuclear antibodies
AIDS, Acquired immunodeficiency Alveolar epithelium, 674 Anasarca, in right-sided heart failure, 533b
syndrome Alveolar rhabdomyosarcoma, 1212f, 1212b Anastomosing capillaries, 674
AIDS-associated (epidemic) KS, 521 Alveolar sacs, 673–674
ANCAs, Antineutrophil cytoplasmic Ankyrin, in hereditary Antiphospholipid antibodies, in systemic
antibodies spherocytosis, 638, 638f lupus erythematosus, 222t, 223–224
Anchoring junctions, 12–13 Anlagen, 1173 Antiphospholipid antibody syndrome, 127–
Ancylostoma duodenale, and parasitic Anoikis, in apoptosis, 308, 315 128, 225
enterocolitis, 796 Anorexia nervosa, 435–436, 436f, 443b Antiplatelet antibodies, 664
Androgen receptor (AR), in prostate Anovulatory cycle, 1003–1004 Antiproteases, in inflammation, 83
cancer, 978–979 Anterior ischemic optic neuropathy Anti-proteinase-3, 510
Androgens, in prostate cancer, 978–979 (AION), 1325–1326, 1326f Antiretroviral drug therapy, for HIV
Anemia(s), 635–661 Anterior subcapsular cataract, 1314– infection, 258–259
aplastic, 659–661, 659t, 660f 1315, 1315f Anti-Sm antibody, in systemic lupus
of blood loss, 636–637, 636t Anterior synechiae, 1314–1315 erythematosus, 222t
of chronic disease, 658–659 Anthracosis, 64, 692b–693b Anti-SS-A antibodies, 230
classification of, 635, 636t Anthrax, 362–363, 363f, 363b Anti-T cell immunotherapy, 580
defined, 635 Anti-apoptotic Bcl family, 44 Antithrombotic events, 119f
of diminished erythropoiesis, 636t, 651–661 Antibodies, structure of, and B-cell antigen Antithrombotic properties, of
due to chronic renal failure, 661 receptor, 196f endothelium, 123–124
due to endocrine disorders, 661 Antibody-dependent cell-mediated α1-antitrypsin, 680–681, 851
due to hepatocellular liver disease, 661 cytotoxicity (ADCC), 192, 209–210 deficiency, 64, 851–852, 851f, 852b
due to pure red cell aplasia, 661 Antibody-mediated glomerular morphology of, 851b
Fanconi, 659 injury, 901t, 902f in inflammation, 83
of folate deficiency, 651t Antibody-mediated (type II) Antitumor effector mechanisms, 311, 311f
from lead, 411 hypersensitivity, 204t, 209–210 Antiviral defense, in innate immunity, 192–
hemolytic, 637–650 examples of, 210t 193
iron deficiency, 655–658, 655t, 657f Antibody-mediated injury, mechanism Aorta, coarctation of, 540–541, 540f
macrocytic, 635 of, 209f Aortic atresia, congenital, 541
megaloblastic, 651–654, 651f–652f, 651t Antibody-mediated reactions, in transplant Aortic dissection, 507–508, 507f–
microcytic hypochromic, 635 rejection, 236 508f, 507b–508b
of iron deficiency, 658f, 658b Antibody-mediated rejection, in cardiac in Marfan syndrome, 149b
myelophthisic, 661 transplantation, 580 Aortic stenosis
normochromic, normocytic, 635 Antibody production, spleen and, 629 calcific, 557–559, 558b
pernicious (vitamin B12 deficiency), 651t, 652– Anticipation congenital, 541
653 in fragile-X syndrome, 175 supravalvular, 541
red cell indices for, 635 in Huntington disease, 1285 valvular, 541
Anencephaly, 1246 Anticoagulant effects Apathetic hyperthyroidism, 1077
Anergy, 217 of endothelium, 123–124 APC, Adenomatous polyposis coli
Aneuploidy, 165 in hemostasis, 122 APCs, Antigen-presenting cells
Aneurysm(s), 487, 504–508, 504f, 508b Antidiuretic hormone (ADH), 1067 Aphthous ulcers, 732–733, 732f
false, 504–505 syndrome of inappropriate secretion of, 1074 Aplasia, 455, 1174
formation of, 499b–502b Anti-dsDNA antibody, in systemic lupus Aplastic anemia, 659–
fusiform, 505 erythematosus, 222t 661, 659t, 660f, 661b–662b
pathogenesis of, 505–506 Antiendothelial cell antibodies, 511 morphology of, 660b
thoracic aortic, 507 Antifibrinolytic effects, of thrombosis, 126 Aplastic crises, 639–640
and thrombosis, 126 Antigen(s), display and recognition of, in in sickle cell disease, 644
Aneurysmal bone cyst, 1194– immune responses, 200 APML, Acute promyelocytic leukemia
1195, 1194f, 1194b Antigen-induced cytosine deaminase Apocrine carcinoma, 1056b–
Angelman syndrome, 178–179, 179f (AID), 315 1058b, 1059f, 1144b–1145b, 1145f
Angiitis, of CNS, primary, 1254 Antigen-negative variants, selective Apocrine cysts, of breast, 1042f
Angina pectoris, 542–543 outgrowth of, in immune evasion, 311 Apoptosis, 15–16, 42–46, 46b
Prinzmetal variant, 543 Antigen-presenting cells (APCs), 203b– causes of, 42–43
stable (typical), 543 204b cytokine T lymphocyte-mediated, 42–43
unstable or crescendo, 543 Antigenic drift, 709 due to protein misfolding, 54, 55f, 55t
Angiodysplasia, intestinal, 783 Antigenic drugs, immunohemolytic evasion of, 343
Angiogenesis, 105–107, 107f anemia, 649 in cancer, 284, 302–303, 303b
in cancer, 284, 305–306, 306b, 315 Antigenic shift, 709 execution phase of, 46
in chronic inflammation, 96 Antigenic variation, 343 extrinsic (death receptor-initiated) pathway
Angiogenic switch, 305–306 mechanisms of, 343t of, 45–46, 46f
Angiomyolipoma, 948 Antiinflammatory cytokine, 107 in immunologic tolerance, 217–218
Angiopoietins 1 and 2 (Ang 1 and Ang Anti-Jo1 antibodies, 1228 intrinsic (mitochondrial) pathway of, 44–
2), 106–107 Anti-Mi2 antibodies, 1228 45, 45f, 302, 302f
Angiosarcoma(s), 522, 522b, 523f Antimicrobial peptides, resistance to, 343 mechanisms of, 44–46, 44f
of breast, 1063 Anti-myeloperoxidase, 510 morphologic and biochemical changes
cardiac, 579 Antineutrophil cytoplasmic antibodies in, 43, 43f, 43b
of liver, 872 (ANCAs), 510–511 p53-induced, 295–296
Angiotensin II, in blood pressure Antinuclear antibodies (ANAs), 221 in pathologic conditions, 42–43
regulation, 491 staining patterns of, 223f in physiologic situations, 42
Angiotensin-converting enzyme (ACE), 491 in systemic lupus erythematosus, 222t removal of dead cells in, 46
Angle-closure glaucoma, 1314 Antioxidants TNF receptor family induced, 45–46
Ankylosing spondylitis, 1202–1203 free radicals removal by, 53 Apoptosome, 45
HLA alleles and, 219t vitamin C, properties of, 449 Apoptotic bodies, 42
Anti-P155/P140 antibodies, 1228 APP, Amyloid precursor protein
Appendage tumors, of skin, 1144–1145 Aryl hydrocarbon receptor interacting pathogenesis of, 497–499
Appendicitis, acute, 818–819, 819b protein (AIP) gene, in pituitary endothelial injury, 497–498, 497f
Appendix, tumors of, 819 tumors, 1069t hemodynamic disturbances, 498
Appositional growth, 1173 Asbestos, 694, 695b infection, 498
APS1, Autoimmune polyendocrine as carcinogen, 280t inflammation, 498, 499f
syndrome type 1 lung diseases due to, 692t lipids in, 498
APS2, Autoimmune polyendocrine pneumoconioses due to, 415 overview, 499
syndrome type 2 related diseases of, 694, 695f smooth muscle proliferation, 498
Aquaporins, 9 Ascaris lumbricoides, and parasitic risk factors for, 494–495, 494t, 495–496, 496–
Aqueous humor, 1313 enterocolitis, 795–796 499
Arachidonic acid (AA) Ascending cholangitis, 839 sequence of cellular interactions in, 500f
in immediate hypersensitivity, 207 bile duct obstruction and, 854, 855f Atherosclerotic disease, consequences
metabolites, in inflammation, 86–88, 87f Ascending (transcending) infections, of, 502–504
actions of, 86t perinatal, 461 Atherosclerotic ischemic renal disease, 939
Arachnodactyly, congenital Ascites, 829 Atherosclerotic plaques, 494, 499b–
contractural, 148–149 in right-sided heart failure, 533b 502b, 503f
Arachnoiditis, chronic adhesive, 1262b Ascorbic acid, 442–443, 442f basic structure of, 494f
Arcuate nucleus, in energy balance, 444– ASD, Atrial septal defect hemorrhage into, 499b–502b
445 Aseptic meningitis, 1262 histologic features of, 501f
ARDS, Acute respiratory distress syndrome Aspergilloma, 387b and ischemic heart disease, 543
Area cerebrovasculosa, in Aspergillosis, 387 rupture of, 502f
anencephaly, 1246 invasive, 387b thrombosis of, 504
Arnold-Chiari malformation, 1247– Aspergillus, 322, 387, 387f–388f, 387b Atherosclerotic stenosis, 502
1248, 1248f Aspergillus fumigatus, 687 ATLL, Adult T-cell leukemia/lymphoma
Array-based comparative genomic Aspirin, 120, 423 Atopy, 208
hybridization, 183 bleeding disorder due to, 667 ATP, depletion of, cell injury due to, 49–
Arrhythmias, 529, 554–555, 554t, 555b mechanism of action of, 88 51, 50f
due to myocardial infarction, 551–552 Asterixis, 827 ATP7B gene, mutation of, 850
Arrhythmogenic right ventricular Asteroid bodies, in sarcoidosis, 696b–697b ATP-binding cassette protein member 3
cardiomyopathy, 572, 572f Asthma, 678t, 683–686, 686b–687b (ABCA3), 700
Arsenic atopic, 683 Atrial fibrillation, in left-sided heart
as carcinogen, 280t clinical features of, 686 failure, 532b
in environmental pollution, 413 drug-induced, 683 Atrial myxomas, 579, 579f
Arterial thrombosis, 130 environmental factors in, 686 Atrial natriuretic peptide, in
Arterial ulcers, 110, 111f genetic susceptibility to, 684 myocardium, 528
Arterioles, 486 non-atopic, 683 Atrial septal defect (ASD), 536–
fibrinoid necrosis of, in malignant normal airway and, 685f 537, 537b, 538f
hypertension, 936b, 938f occupational, 683–684 Atrioventricular (AV) node, 528
Arteriolosclerosis, 1108b–1109b organic dusts that induce, 692t Atrophic glossitis, due to vitamin
Arteriosclerosis, 493 pathogenesis of, 684–686 B12 deficiency, 654b
hyaline, in benign nephrosclerosis, 935f Astrocytes, 1242, 1243f Atrophy, 59–60, 60f
Arteriovenous fistulas, 487 Alzheimer type II, 1243 of caudate nucleus, 1286b
Arteriovenous malformations gemistocytic, 1242 mechanisms of, 60
(AVMs), 1260f, 1260b reactions to injury of, 1242 ATRX, Alpha-thalassemia/mental
Arteritis Astrocytoma, 1293–1295 retardation syndrome, X-linked
giant cell, 511–512 diffuse, 1294f, 1294b–1295b Atypical ductal hyperplasia, 1045, 1045f
Takayasu, 512 gemistocytic, 1294b–1295b Atypical lobular hyperplasia, 1045, 1045f
Arthritis, 1206b–1207b infiltrating, 1293–1294 Atypical lymphocytes, in infectious
acute, 1205, 1205b pilocytic, 1296, 1296b, 1297f mononucleosis, 357–358, 358f, 358b
chronic tophaceous, 1205, 1205b Asymmetric division, of stem cells, 28 Atypical meningiomas, 1300b–1301b
crystal-induced, 1204–1206 Asymptomatic hyperparathyroidism, 1095 Atypical parkinsonism syndromes, 1284–
infectious, 1203–1204 Ataxia-telangiectasia, 314, 1148t, 1287 1285
juvenile idiopathic, 1202 Atelectasis (collapse), 674–675, 675f Autocrine signaling, 17
Lyme, 1203–1204 ATG16 gene, autoimmune diseases Autoimmune adrenalitis, 1123
mycobacterial, 1203 and, 219t Autoimmune cholangiopathies, 857–859
osteoarthritis, 1198–1199, 1198f–1199f, 1198b Atheroembolic renal disease, 939, 940f Autoimmune diabetes, 1110f
reactive, 1203 Atheroembolism, 499b–502b Autoimmune diseases, 215–234, 215t, 702
rheumatoid, 691, 1199–1202, 1199f– Atheromas, 494 general features of, 221
1202f, 1201b Atheromatous plaques, 494 HLA alleles and, 218–219
secondary osteoarthritis, 1198 Atherosclerosis, 63, 493–504, 495f, 499b– infections and, 220, 220f
suppurative, 1203 502b, 501f, 503f, 504b inflammation due to
viral, 1203 chronic inflammation in, 96 acute, 74
Arthropod-borne viral cigarette smoking and, 417 chronic, 96
encephalitis, 1264, 1264b–1265b diet and, 450 inflammatory myopathies, 234
Arthus reaction, 211t, 212 epidemiology of, 494 lupus erythematosus
Artifact, 613f, 1150f and ischemic heart disease, 542 chronic discoid, 229
Artificial heart valves, complications morphology of, atherosclerotic plaques drug-induced, 229
of, 566f in, 494, 499b–502b subacute cutaneous, 229
hemorrhage into, 499b–502b systemic, 221–229
histologic features of, 501f mixed connective tissue disease, 234
non-HLA genes associated with, 219t B cells, 326, 357, 1224 Basement membrane, 23, 674
non-MHC genes and, 219–220 B lymphocytes BAX gene, 295–296
polyarteritis nodosa and other vasculitides, 234 activation of, 201–203 B-cell acute lymphoblastic
systemic, autoantibodies in, 222t in immune response, 195–196, 203b–204b leukemia/lymphoma, 595t
systemic sclerosis (scleroderma), 231–234 naive, 202f B-cell lymphomas, in AIDS, 257f
Autoimmune enteropathy, 786 recognition of graft alloantigens by, 234–235 BCG, Bacillus Calmette-Guérin
Autoimmune hemolytic anemia, 210t Babesia divergens, 390 BCL2 oncogene, in apoptosis, 44–45, 45f
Autoimmune hepatitis, 839–841, 840f, 841b Babesia microti, 390 BDNF, Brain-derived neurotrophic factor
morphology of, 839b–840b Babesiosis, 390, 390b, 391f Becker muscular dystrophy, 1232
Autoimmune hypoparathyroidism, 1096 Bacillary angiomatosis, 520, 521f morphology of, 1232b–1233b
Autoimmune hypothyroidism, 1077 Bacillus anthracis, 364f Bellini duct carcinoma, 950
Autoimmune lymphoproliferative syndrome Bacillus Calmette-Guérin (BCG), for Bence-Jones proteins, 261–262, 607, 934
(ALPS), 217–218 bladder cancer, 961–962 Bence-Jones proteinuria, and light-chain
Autoimmune orchitis, 968 Bacteria cast nephropathy, 934
Autoimmune pancreatitis, 886, 886b–887b anaerobic, 379–380 Bends, the, 132
Autoimmune polyendocrine syndrome type in sexually transmitted diseases, 400t Benign familial hematuria, 922–923
1 (APS1), 1123 Bacterial adherence, to host cells, 346 Benign metastases theory, of
Autoimmune polyendocrine syndrome type Bacterial infections, 359–382, 359t endometriosis, 1005
2 (APS2), 1123 anaerobic, 379–380 Benign neoplasms, in liver, 866–867, 866f
Autoimmune pulmonary alveolar anthrax, 362–363, 363f, 363b Benign prostatic hyperplasia
proteinosis, 700 chancroid (soft chancre), 367, 367b (BPH), 59, 976–977, 976f, 977b
Autoimmune regulator (AIRE) protein, in chlamydial, 381, 381b Benign teratomas, 1023f–1024f, 1023b–
immunological tolerance, 216 clostridial, 380, 380b–381b 1024b
Autoimmune thrombocytopenic diphtheria, 361–362, 362f, 362b Benign tertiary syphilis, 376
purpura, 210t Gram-negative, 364–367 Benign tumors
Autoimmunity, 189 Gram-positive, 359–364 characteristics of malignant and, 270–
immunologic tolerance and, 216– granuloma inguinale, 367, 367b 276, 276t, 276b–277b
218, 216f, 221b leprosy, 374, 374b–375b differentiation and anaplasia, 270–273, 271f, 276t
infections and, 220–221, 220f listeriosis, 362, 362b local invasion, 273, 276t
mechanisms of, 218–221 Lyme disease, 378–379, 379b metastasis, 273–276
pathogenesis of, 218f neisserial, 364–365 defined, 268
susceptibility genes in, 218–220 Nocardia, 363–364, 364b nomenclature for, 268–270
in systemic sclerosis, 231–232 obligate intracellular, 381–382 Benzene
Autoinducer peptides, 346 pertussis, 365, 365b as carcinogen, 280t
Autoinflammatory syndromes, 74, 191–192 plague, 366–367, 367b lung diseases due to, 692t
Autonomic nerves, 1217 Pseudomonas, 366b occupational health risks, 414–415
Autophagy, 15, 35, 48–49, 48f, 49b rickettsial, 382 Berger disease, 920–922, 921f, 921b
in inflammatory bowel disease, 800 staphylococcal, 359–360, 359f, 361f Bergmann gliosis, 1292
in tumor cells, 300 streptococcal and enterococcal, 360–361 Bernard-Soulier syndrome, 666
Autoregulation, in blood pressure syphilis, 375–377, 377b–378b Berry aneurysms, 487
regulation, 490–491 tuberculosis, 368–371, 369f, 372f Beryllium
Autosomal dominant disorders, 144– Bacterial injury, mechanisms of, 345–347 as carcinogen, 280t
145, 145t Bacterial meningitis, 1262 lung diseases due to, 692t
Autosomal-dominant Bacterial toxins, 346 pneumoconioses due to, 415
hypoparathyroidism, 1097 Bacterial vasculitis, 366f, 366b BH3-only proteins, in apoptosis, 45
Autosomal dominant (adult) polycystic Bacterial virulence, 345–346 Bicuspid aortic valve, calcific stenosis
kidney disease, 941–943, 941f– Bagasse, hypersensitivity pneumonitis due of, 559
943f, 941t, 942b to, 692t Bilateral idiopathic
Autosomal recessive disorders, 145– Baker cyst, 1207 hyperaldosteronism, 1118
146, 146t Balanced reciprocal translocation, 166, 166f Bilateral idiopathic hyperplasia, 1119b
Autosomal recessive (childhood) polycystic Balanoposthitis, 963–964 Bile, hepatic, 852
kidney disease, 941f, 941t, 943–944 Balloon angioplasty, 523 Bile cast nephropathy, 935
Autosomal recessive severe combined “Ballooned” neurons, in corticobasal Bile duct obstruction, 854f, 859b
immunodeficiency, 242 degeneration, 1284b morphology of, 854b, 855f
Autosplenectomy, in sickle cell Ballooning, 1135t Bile formation, 852–853
disease, 642b, 643f Band keratopathies, corneal Biliary adenocarcinoma, 871
Avascular necrosis, 1185, 1185f, 1185b degenerations, 1311 Biliary atresia, 856
AVMs, Arteriovenous malformations Barium sulfate, lung diseases due to, 692t morphology of, 856b
Axillary lymph node, involvement of, in Barrett esophagus, 761–762, 761f– Biliary cirrhosis, 855f
breast carcinoma, 275f, 1058–1059 762f, 761b–762b Biliary tree, structural anomalies of, 859–
“Axillary tail of Spence,”, 1038 Bartholin cyst, 990 860
Axon terminals, 1067 Bartonella henselae, 520 Bilirubin, 852
Axonal neuropathies, 1218, 1219f–1220f Bartonella quintana, 520 metabolism and elimination of, 852f
Axonal reaction, 1242b Basal cell carcinoma Binge eating, 436
Azotemia, 896–897 of eyelid, 1308 Bioaerosols, in indoor air pollution, 410
Azurophil granules, in inflammation, 83 of skin, 1147–1148, 1148b–1149b, 1150f Biofilms, 346
of vulva, 989–990 Bioinformatics, 185–186
Base pair Bioterrorism, agents of, 401
human genome, 1 Bird droppings, hypersensitivity
B nucleosomes, 3 pneumonitis due to, 692t
Bird fancier's disease, 698 pathology of vascular intervention for, 523 homeostasis and remodeling of, 1173–
Birth weight, 475 Raynaud phenomenon, 516–517, 516f 1174, 1174f–1175f
Bisphenol A (BPA), 415 response to injury of, 487–489 metabolic diseases of, 1179–1183, 1182b
Bitemporal hemianopsia, 1067 structure and function of, 485–487, 487b osteomyelitis of, 1185–1187, 1186f, 1186b
Bitot spots, 437–438, 438f tumor(s) of, 518–520 osteonecrosis of, 1185, 1185f, 1185b
Black Death, 366 benign, 518–520, 520b tumors and tumor-like lesions, 1187–
Bladder, 955–962 bacillary angiomatosis, 520 1196, 1187t, 1197b
anatomy of, 953 glomus tumor (glomangioma), 520 Bony ankylosis, 1201b
congenital anomalies of, 955, 955f hemangioma, 519–520 Border zone (“watershed”)
diverticula of, 955 lymphangiomas, 520 infarcts, 1256, 1256f
exstrophy of, 955, 955f intermediate-grade (borderline) tumors of, 520–522 Bordetella pertussis, 365, 365b
inflammation of, 955–957, 956f hemangioendothelioma, 522 Borrelia burgdorferi, 378, 1203
inflammatory disorders and metaplasias, 957bKaposi sarcoma, 520–521 Botox, 1226
metaplastic lesions of, 957 malignant, 522 Botulism, 380, 1226
obstruction of, 962 angiosarcoma, 522, 523f Bowen disease, of penis, 965, 965f
morphology of, 962b vascular anomalies, 487 Bowenoid papulosis, 965, 1167
Bladder carcinoma in situ, 960f vasculitis of, 508–516 Bowman layer, 1310
Bladder tumors, 957, 957t, 962b Buerger disease, 515 BPD, Bronchopulmonary dysplasia
classification of, 961t Churg-Strauss syndrome, 515 BPH, Benign prostatic hyperplasia
mesenchymal, 962 giant cell, 511–512 Brachydactyly, 1176t
secondary, 962 immune complex-associated, 509–510 types D and E, 1175
urothelial (transition), 957–962 infectious, 516 Bradykinin, in inflammation, 92
Blastomyces dermatitidis, 712–713 Kawasaki diseases, 513 BRAF gene, oncogenic, 287
Bleeding disorder(s), 635–672 microscopic polyangiitis, 513–514 Brain abscess, 1262–1263, 1263f, 1263b
caused by vessel wall abnormalities, 663 noninfectious, 509–516 Brain-derived neurotrophic factor (BDNF),
disseminated intravascular coagulation, 669– polyarteritis nodosa, 513 in energy balance, 445–446
671 Bloodstream expression sites, 392 Brain edema, 117b
due to defective platelet functions, 666–667 Bloodstream parasites, of African Brain injury
hemorrhagic diatheses, 662–672 trypanosomiasis, 392, 393f concussion, 1249
related to abnormalities in clotting factors, 667– Bloom syndrome, 314 contusions, 1249
669, 667f “Blue bloaters,”, 682 coup, and contrecoup, 1249
related to reduced platelet number, 663– Blue-dome cysts, of breast, 1042f, 1042b diffuse axonal, 1250
666, 664t Blue nevus, 1136t lacerations, 1249
Blepharitis, 1307–1308 BMPR2, Bone morphogenetic protein parenchymal, 1249–1250
Blister, 1135t, 1159f receptor type 2 perinatal, 1248
Blistering disorders, 1165b BMPs, Bone morphogenic proteins sequelae of, 1252
inflammatory, 1159–1163 Body mass index (BMI) skull fractures, 1249
bullous pemphigoid, 1162–1163 and malnutrition, 444 vascular, 1250–1252
dermatitis herpetiformis, 1163 and obesity, 444 Brain stem, 474–475
pemphigus, 1159–1162 Boil, 360b Branchial cyst, 745
noninflammatory, 1163–1164, 1163f Bone, mineralization of, 440, 441f BRCA1, 314–315
epidermolysis bullosa, 1163–1164 Bone disease(s), in and breast cancer, 1047, 1049t
porphyria, 1163–1164 hyperparathyroidism, 1096 BRCA2, 314–315
Blood-brain barrier, 487, 1244 Bone-forming tumors, 1187–1189, 1197b and breast cancer, 1047, 1049t
Blood cell progenitors, 590 osteoblastoma, 1188, 1188b and prostate cancer, 978
Blood cells osteoid osteoma, 1188, 1188f, 1188b Breakdown products, lipid, 51
adult reference ranges for, 584t osteosarcoma, 1188–1189, 1189f, 1189b Breast, 1037–1064
differentiation of, 585f Bone marrow, 585b–586b anatomy of, 1037, 1038f
phagocytosis of, 629 in sarcoidosis, 696b–697b developmental disorders of, 1038
Blood clots Bone matrix, 1171–1172 fibroadenoma, of, 273f
postmortem, 128b–129b Bone morphogenetic protein receptor type 2 invasive ductal carcinoma of, 273–276
in thrombosis, 118 (BMPR2), 703 life cycle changes in, 1038f
Blood flow, alterations in, in Bone morphogenic proteins (BMPs), 1173 male, 1061
thrombosis, 126 Bones, 1171–1215 supernumerary, 1038
Blood loss basic structure and function of, 1171–1174
acute, 636–637 cells of, 1172–1173
anemias of, 636–637, 636t development of, 1173 Breast carcinoma, 1046–1061, 1053b
chronic, 637 developmental disorders of, and basal-like, 1047, 1048f
Blood pressure regulation, 490–492, 492b cartilage, 1174–1178, 1176t, 1178b comedo, 1053b–1054b, 1054f
Blood supply, to heart, 528–529 degradation of macromolecules, diseases associated contralateral, 1054–1055
Blood vessel(s), 485–525 with defects in, 1178 development of, 1050f
abdominal aortic aneurysm, 506–507 extracellular structural proteins, defects in, 1175– ductal
aneurysms and dissection of, 504–508 1176 invasive (infiltrating), 1055, 1057f
arteriosclerosis of, 493 hormones and signal transduction proteins, defects in situ, 1053, 1054f–1055f
atherosclerosis of, 493–504 in, 1175 epidemiology of, 1046
hyperactivity of, disorders of, 516–517 metabolic pathways, defects in, 1176–1178 estrogen receptors in, 1045, 1060
in inflammation nuclear proteins and transcription factors, defects gene expression profiling for, 1057f, 1060
acute, 75–76 in, 1174–1175 grading of, 1058f, 1060
chronic, 96 fractures of, 1183–1185 HER2-positive, 1046, 1048f, 1051, 1051f–
myocardial vessel vasospasm, 517 1052f, 1056b–1058b, 1060–1061
hereditary, 1047, 1049t granulomatous, 1041 Cadherins, 12–13
incidence of, 1046, 1046f periductal, 1040 Cadmium
inflammatory, 1060 lymphomas, 1063 as carcinogen, 280t
invasive (infiltrating), 1055, 1059t male, 1061 in environmental pollution, 413–414
ductal (no special type), 1055, 1058f carcinoma, 1061 Café au lait spots, 1302
lobular, 1056 gynecomastia, 1044, 1044f Caisson disease, 132
papillary, 1056b–1058b metastases, 1058–1059 Calcific band keratopathy, 1311
lobular stromal tumors, 1061–1063, 1063b Calcification(s)
invasive, 1056 benign, 1062 of breast, 1039–1040
in situ, 1055, 1056f fibroadenoma, 1062, 1062f pathologic, 65–66, 66b
locally advanced, 1060 malignant, 1063 Calciphylaxis, 1096
luminal, 1051, 1051f phyllodes tumor, 1062–1063, 1063f Calcitonin, 1075
lymphovascular invasion by, 1060 Breast milk, 1040 Calcium
male, 1061 Breast pain, 1038–1039 blood, interaction of PTH in regulation of, 440
medullary, 1056, 1059f Breast tissue, accessory axillary, 1038 reabsorption, in kidney, stimulation of, 440
metaplastic, 1056b–1058b Breastfeeding, and breast cancer, 1046–1047 Calcium homeostasis
metastatic, 1058–1059 Brenner tumors, 1022, 1022f loss of, cell injury due to, 54, 54f
molecular mechanisms of carcinogenesis and Bridging veins, in subdural hematoma, 1251 vitamin D in, 440
tumor progression, 1047–1053, 1048f Broad-spectrum antibiotics, 587 Calcium influx, cell injury due to, 54, 54f
mucinous (colloid), 1056b–1058b, 1059f Bronchiectasis, 678t, 687–688, 687b– Calcium nutritional state, 1179–1180
neoadjuvant therapy for, 1060 688b, 688f Calcium oxalate stones, 947, 947t
no special type, 1055, 1058f Bronchioles, 673–674 Calcium pyrophosphate crystal deposition
occult, 1055b–1056b Bronchiolitis, 678t, 710b disease, 1205–1206
oral contraceptives and, 422 Bronchiolitis obliterans organizing Call-Exner bodies, in granulosa cell
papillary, 1056b–1058b pneumonia, 690–691 tumors, 1026b
pathogenesis of, 1047–1053 Bronchopulmonary dysplasia (BPD), in Calor, 73, 95–96
prognostic and predictive factors in, 1058– neonatal respiratory distress Caloric restriction, in cellular aging, 68
1061, 1061b syndrome, 460 Calyx(ces), 930f, 946f
proliferative rate of, 1060 Brown atrophy, 60 Camptomelic dysplasia, 1176t
risk factors for, 1046–1047, 1047t Brown tumor, 1094b–1095b, 1181f, 1181b CAMs, Cell adhesion molecules
screening for, 1038–1039, 1039f, 1046 Brunn nests, 957 Canalicular cholestasis, 855
in situ, 1053–1055 Bubonic plague, 367b Canals of Hering, 104–105
ductal, 1053, 1054f–1055f Budd-Chiari syndrome, 862, 862f, 862b Cancer
lobular, 1055, 1056f Buerger disease, 515 alcohol consumption and, 278
sporadic, 1049–1053 Bulbar conjunctiva, 1308–1309 benign tumors and, 270–276, 276t, 276b–277b
staging of, 1060t–1061t Bulimia, 435–436 cachexia due to, 328
susceptibility genes for, 1047, 1049t Bulla, 1135t carcinogenic agents in, 320–327
triple negative, 1046, 1051f, 1055b–1056b Bullous pemphigoid, 1162– chemical, 321, 321f, 321t, 322b
tubular, 1056b–1058b, 1059f 1163, 1162f, 1162b direct-acting, 322
tumor size in, 1059–1060 Bundle of His, 528 indirect-acting, 322
types of, 1050t, 1053–1061, 1061b Buphthalmos, 1326b microbial, 323–327
Breast changes, nonproliferative Burkitt lymphoma, 595t, 601– radiation, 323
(fibrocystic), 1042, 1045t 602, 602f, 602b, 604b–605b categorization of undifferentiated, 332
Breast cysts, 1042f, 1042b Epstein-Barr virus and, 325, 326f, 357–358 cell cycle and inhibitors in, 290t
Breast disease Burns, thermal, 427 cell-like properties of, 303–305
benign epithelial, 1042–1045, 1045b Byproduct characteristics of, 270–276, 276t, 276b–277b
adenosis, 1042b sulfur dioxide, 409 differentiation and anaplasia, 270–273, 271f, 276t
sclerosing, 1043f, 1043b xenobiotics, 408 local invasion, 273, 276t
atypical ductal hyperplasia, 1045, 1045f metastasis, 273–276
atypical lobular hyperplasia, 1045, 1045f chronic inflammation and, 280, 281t
clinical significance of, 1045, 1045t classification of, 335f
complex sclerosing lesion, 1043b, 1044f C clonal expansion of, 282
cysts, 1042f, 1042b C chemokines, 90 defined, 268
epithelial hyperplasia, 1043f, 1043b C1 inhibitor (C1 INH), in complement detection of molecules of prognostic or
fibrosis, 1042b system, 91 therapeutic significance in, 332
lactational adenomas, 1042b C3 convertase, 91 development of, 282f
nonproliferative (fibrocystic) changes, 1042, 1045t C3α, 91 diet and, 278, 449
papillomas, 1043b, 1044f C3β, 91, 346 enabling inflammation and, 315–316
proliferative changes C4α, 91 epidemiology of, 277–281, 281b
with atypia, 1044–1045, 1045t C5 convertase, 91 acquired predisposing conditions in, 279–281
without atypia, 1042–1044, 1045t C5α, 91 age in, 278–279
calcifications due to, 1039–1040 C-21 hydroxylase deficiency, 1120f, 1121 environmental factors in, 278
clinical presentations of, 1038–1040, 1039f CAA, Cerebral amyloid angiopathy genetic predisposition in, 281
densities due to, 1039 Cachectin, in cachexia, 328 geographic variation in, 279f
inflammatory, 1040–1041 Cachexia, 89–90, 435 global impact of, 277–278
duct ectasia, 1041, 1041f due to cancer, 328 incidence in, 277, 277f
fat necrosis, 1041 CACNA1S, mutations of, 1236 grading and staging of, 330
lymphocytic mastopathy, 1041 CADASIL, Cerebral autosomal dominant growth factor signaling pathways in, 286f
mastitis arteriopathy with subcortical infarcts and hereditary predisposition to, 333
acute, 1040 leukoencephalopathy host defense, evasion of
antitumor effector mechanisms in, 311, 311f environmental, 278 Cartilage, developmental disorders
immune surveillance and escape, 309–313, 313b indirect-acting, 322 of, 1174–1178
mechanisms of, 311–313, 313f ultimate, 322 Cartilage-forming tumors, 1189–
tumor antigens in, 309–310, 310f Carcinoid heart disease, 565, 565b, 566f 1192, 1197b
laboratory diagnosis of, 331–336, 336b Carcinoma en cuirasse, 1060 chondromas, 1190–1191
molecular basis of, 281–320 Carcinoma in situ, 272–273, 273f chondrosarcoma, 1191–1192, 1192f
angiogenesis in, 284, 305–306, 306b, 315 of bladder, 957–958, 958f, 959b–960b osteochondroma, 1189–1190, 1190f, 1190b
cellular and molecular hallmarks of, 284, 284f of breast Caruncle, urethral, 963
chromosomal changes in, 316–318 ductal, 1053, 1054f–1055f Caseous necrosis, 40b–41b, 41f
chromosomal translocations in, 316–317 lobular, 1055, 1056f Caspases, in apoptosis, 44, 302–303
dysregulation of cancer-associated genes in, 316– of penis, 964–965, 964f, 966t, 966b Catalase, 83
320 Carcinomas, 269 in alcohol metabolism, 418–419
epigenetic changes in, 319–320 Carcinosarcomas, of endometrium, 1012 Cataract, due to diabetes mellitus, 1108b–
evasion of apoptosis in, 284 Cardiac atrophy, 536 1109b
gene amplification in, 317–318 Cardiac cirrhosis, in right-sided heart Catecholamine cardiomyopathy, 1129
genetic lesions in, 318b failure, 533b β-catenin gene, 297, 298f
genomic instability in, 284, 314–315, 315b Cardiac conduction system, 528 Cathelicidins, in phagocytosis, 83
immunodeficiency states and, 280–281 Cardiac devices, 580–581 Cationic trypsinogen gene, in
invasion and metastasis in, 284, 309b, 315–316 Cardiac dilation, 528 pancreatitis, 882t
local and hormonal effects of, 328 Cardiac hypertrophy, 58–59, 528, 530– Cat-scratch disease, 520
microRNAs (miRNAs) in, 320 532, 532f Caveolae, 11
as multistep, 320 left ventricular, 531f Cavernous hemangiomas, 520
mutations in, 282–283 physiologic, 532 Cavernous lymphangiomas, 520
noncoding RNAs and, 320 pressure-overload, 530 Cavernous malformations, of brain, 1260b
oncogenes in, 284–286, 285t, 286–290 volume-overload, 530 CBD, Corticobasal degeneration
tumor suppressor genes in, 291–299, 292t Cardiac hypoplasia, 536 C-C chemokines, 90
Warburg effects in, 299–302, 302b Cardiac myocytes, 528 CCPs, Citrullinated peptides
molecular profiles of, 334–335 Cardiac output, in blood pressure CCR5, in West Nile virus, 345
nomenclature for, 268–270 regulation, 490, 490f CD+ T cell-mediated inflammation, 212–
obesity and, 278, 448–449, 448f Cardiac pathophysiology, 529–530 214
occupational, 280t Cardiac Raynaud, 517 CD4+ helper T cells
paraneoplastic syndromes due to, 328–330, 329t Cardiac regeneration, 529 activation of, 212
precursor lesions and, 280 Cardiac stem cells, 529 evasion of recognition by, 344
promoting inflammation and, 284 Cardiac thrombosis, 130 in immune responses, 200–201, 203b–204b
reproductive history and, 278 Cardiac transplantation, 580, 581f in systemic lupus erythematosus, 224
risks from exposures to radiation, 432–433 Cardiac tumors CD4+ T cell-mediated inflammatory
tumor markers for, 335–336 metastatic, 580 reactions, clinical examples of, 214
Cancer immunoediting, 309 primary, 579–580, 579f CD8+ cells, 195, 212
Cancer stem cells, 282 Cardiac valves, 528 CD8+ cytotoxic T cell-mediated cell
Cancer-testis antigens, 310 aging effect on, 529 death, 1079
Candida albicans, 384 Cardiogenic shock, due to myocardial CD8+ T cell-mediated cytotoxicity, 214–
esophagitis, 384b–385b infarction, 551 215
vaginitis, 384b–385b Cardiomegaly, 528 CD28, in anergy, 217
Candida esophagitis, 384f Cardiomyopathies, 567–577, 567t– CD46, 350
Candidiasis, 383–385, 384f, 384b–385b 568t, 568f, 577b CDK4, in osteosarcoma, 1188
in AIDS, 256 Cardiotoxic drugs, myocardial disease due CDKN1B (p27/KIP1) gene, in pituitary
cutaneous, 384b–385b to, 577 tumors, 1069t
invasive, 384b–385b Cardiovascular disease CDKN2A gene, 298
Canker sores, 732, 732f and chronic alcoholism, 420 in dysplastic nevi, 1138–1140
Capillaries, structure and function of, 487 climate change and, 406 in pancreatic carcinoma
Capillary hemangiomas, 519–520 oral contraceptives in, 422 CDKs, Cyclin-dependent kinases
Capsule, 273 Cardiovascular lesions, 149b Celiac disease
Carbon dioxide (CO2), in greenhouse Cardiovascular syphilis, 376 HLA alleles and, 219t
effect, 406 Cardiovascular system, in systemic lupus malabsorption and diarrhea in, 784–786, 784f–
Carbon monoxide erythematosus, 225b–228b 785f, 785b
as air pollutant, 410, 410b Caries, 731 Cell
CNS toxicity of, 1292 Carney complex, cardiac myxomas in, 579 basic subcellular constituents of, 7f
Carbon tetrachloride, occupational health Carney triad, gastrointestinal stromal tumors and extracellular matrix interactions, 26f
risks, 414–415 in, 778 as a unit of health and disease, 1–31
Carbonic anhydrase 2 (CA2) gene, 1176– Carnitine palmitoyltransferase II waste disposal of, 14–15
1177 deficiency, 1234 Cell adhesion molecules (CAMs), 24–25
Carbuncle, 360b Caroli syndrome, 860 Cell-cell interactions, 11f, 12–13
Carcinogenesis β-carotene, 436, 449 Cell cycle, 25–28
chronic alcoholism and, 420 Carotenoids, 436 landmarks, 26f
diet and, 449 Carotid body tumor, 746, 746f, 746b Cell damage, sensors of, 74
DNA damage and, 432 Carpal tunnel syndrome, 1224 Cell death, 16, 35
molecular basis of multistep, 320 Carrier males, of fragile-X syndrome, 175 causes of, 36
nonlethal genetic damage in, 281 Carrier proteins, 9 enhanced resistance to, 315
Carcinogens Carrier state, in viral hepatitis, 837 via apoptosis, morphologic alterations in, 37t
direct-acting, 322 via necrosis
clinicopathologic correlations of, 55–57 adaptations of cellular growth and amyotrophic lateral sclerosis, 1287–1288, 1288f
morphologic alterations in, 36, 37t differentiation, 57–61 ataxia-telangiectasia, 1287
overview of, 35 apoptosis, 42–46, 46b atypical parkinsonism syndromes, 1284–1285
Cell-derived mediators, of autophagy, 35, 48–49, 48f, 49b corticobasal degeneration, 1284
inflammation, 85–86 cellular aging, 66–69, 69b Friedreich ataxia, 1287
arachidonic acid metabolites, 86–88 intracellular accumulations, 62–65, 66b frontotemporal dementia, 1280
cytokines and chemokines, 88–90 pathologic calcification, 65–66 Huntington disease, 1285–1286, 1286f
neuropeptides, 92 Cellular stress response, in inflammatory of motor neurons, 1288–1289
nitric oxide, 83 bowel disease, 800 multiple system atrophy, 1284–1285, 1285b
platelet-activating factor, 92 Cellular swelling, in cell injury, 36, 37b Parkinson disease, 1282–1284, 1283f
vasoactive amines (histamine and serotonin), 86 Celsus, 73 Pick disease, 1280b
β-cell destruction, mechanism of, in type 1 Central artery, of eye, 1306f progressive supranuclear palsy, 1284
diabetes mellitus, 1102–1103 Central-core disease, 1231t spinal and bulbar muscular atrophy (Kennedy
Cell differentiation, vitamin A in, 437 Central nervous system (CNS), 1241–1304 disease), 1289
β-cell dysfunction, in diabetes cellular pathology in, 1242–1243, 1243b–1244b spinal muscular atrophy, 1289
mellitus, 1105 cerebral edema, 1244–1245, 1245b spinocerebellar, 1286–1287
β-cell function, genetic defects in, 1105 cerebrovascular disease, 1253– perinatal brain injury, 1248, 1252b–1253b
Cell growth 1260, 1260f, 1260b raised intracranial pressure and
metabolism and, in cancer, 301f hypoxia, ischemia, and infarction, 1254f herniation, 1244–1245, 1245f, 1245b
vitamin A in, 437 hypoxia and ischemia, 1253–1256, 1255f toxic, 1291–1293, 1293b
Cell injury, 33–69, 34f–35f intracranial hemorrhage, 1257–1260, 1258f trauma, 1249–1252
causes of, 36 demyelinating, 1269–1273, 1273b concussion, 1249
chemical (toxic), 56–57 acute disseminated encephalomyelitis, 1272 diffuse axonal injury, 1250
clinicopathologic correlations of, 55–57 acute necrotizing hemorrhagic parenchymal injuries, 1249–1250
irreversible, 39f encephalomyelitis, 1272 sequelae of, 1252
ischemia-reperfusion, 56 central pontine myelinolysis, 1272–1273 skull fractures, 1249
ischemic and hypoxic, 55–56, 57b multiple sclerosis, 1269–1272, 1271f–1272f vascular injury, 1250–1252, 1251t
mechanisms of, 49–54, 54b, 56f neuromyelitis optica, 1272 tumors, 1293–1303, 1303b
accumulation of oxygen-derived free radicals hydrocephalus, 1244–1245, 1245b astrocytoma, 1293–1295, 1294f, 1297f
(oxidative stress), 52–53, 52t, 53f infections in, 1261–1269, 1261t, 1269b ependymoma, 1296–1298, 1297f
calcium homeostasis disturbance, 54, 54f abscess familial tumor syndromes of, 1302–1303
defects in membrane permeability, 51, 51f brain, 1262–1263 gliomas, 1293–1298
depletion of ATP, 49–51, 50f extradural, 1263 medulloblastoma, 1298–1299, 1299f
mitochondrial damage, 49–51, 50f acute focal suppurative, 1262–1263 meningiomas, 1300–1301, 1300f
progression of, 36–37, 37f–38f, 37t, 42b acute meningitis, 1261–1262 metastatic, 1301
reversible, 35, 37, 38f–39f meningoencephalitis neurofibromatosis, 1302
Cell lysis, complement system in, 91 chronic bacterial, 1263–1264 neuronal, 1298
Cell-mediated immunity, 200– fungal, 1268 paraneoplastic syndromes due to, 1301–1302
201, 201f, 203b–204b viral, 1264–1268 primary CNS lymphoma, 1299–1300
in glomerulonephritis, 904 protozoal, 1268–1269 Central pontine myelinolysis, 1272–1273
Cell populations subdural empyema, 1263 Central tolerance, 216–217
maintaining, 25–30 injury, spinal cord, 1252 Central vein, of eye, 1306f
mechanisms regulating, 28f involvement Centrilobular necrosis, 863
Cell proliferation, 25 in AIDS, 258 in right-sided heart failure, 533b
signals and control mechanisms of, 103–104 pathogenesis of, 253 Centroblasts, 599b
Cell shrinkage, in apoptosis, 43f, 43b in systemic lupus erythematosus, 225b–228b Centrocytes, 599b
Cell signaling, 17 malformations and developmental Centronuclear myopathy, 1231t
δ-cell tumors (somatostatinomas), 1114 diseases, 1245–1248, 1248b Cerebral amebiasis, 1269, 1269f
α cells, of pancreas, 1097 of forebrain, 1246–1247 Cerebral amyloid angiopathy
β cells, 1097 neural tube defects, 1245–1246 (CAA), 1257, 1278b
δ cells, 1097 of posterior fossa, 1247, 1248f Cerebral autosomal dominant arteriopathy
Cell-surface receptors, 17 syringomyelia and hydromyelia, 1248 with subcortical infarcts and
Cellular activation, 16–20 metabolic diseases leukoencephalopathy (CADASIL), 1257
Cellular adaptations, to stress, 61b acquired, 1291–1293, 1293b Cerebral edema, 1244
Cellular aging, 66–69, 67f, 69b Alexander disease, 1290 Cerebral infarction, 1253–1254, 1254f–
Cellular dysfunction, in antibody-mediated due to hyperglycemia, 1292 1255f
hypersensitivity, 210 due to hypoglycemia, 1292 due to global cerebral ischemia, 1256
Cellular housekeeping, 6–15, 7f due to vitamin deficiencies, 1291–1292 hemorrhagic, 1258f
Cellular metabolism, 15–16 genetic, 1289–1291, 1291b nonhemorrhagic, 1254b–1255b
altered, in cancer, 284 hepatic encephalopathy, 1292 Cerebral ischemia, 1253–1256
Cellular proteins, overexpressed or Krabbe disease, 1290, 1290f focal, 1253–1254
aberrantly expressed, as tumor Leigh syndrome, 1291 global, 1256
antigens, 310 leukodystrophies, 1290 Cerebral malaria, 1269
Cellular receptors, for microbes, products of mitochondrial encephalomyopathies, 1290–1291 malignant, 390f, 390b
damaged cells and foreign myoclonic epilepsy and ragged red fibers, 1291 Cerebral palsy, 1248
substances, 191–192, 191f, 193f neuronal storage diseases, 1289 Cerebral toxoplasmosis, 1269, 1269f, 1269b
Cellular rejection, 580 Pelizaeus-Merzbacher disease, 1290 Cerebrospinal fluid (CSF), Guillain-Barré
Cellular responses Tay-Sachs disease, 1289 syndrome and, 1221
to stress and noxious stimuli, 34–37, 34f, 37t neurodegenerative, 1273–1289, 1274t, 1289b Cerebrovascular disease, 1252b, 1253–
to stress and toxic insults, 33–69 Alzheimer disease, 1275–1280, 1277f–1279f 1260, 1260b–1261b
and climate change, 406 benign, 475–477, 476f Chronic bronchitis, 678t, 681–
hypoxia, ischemia, and infarction, 1254f malignant, 477, 477t 682, 681b, 682t
hypoxia and ischemia, 1253–1256, 1255f CHIP, Clonal hematopoiesis of Chronic cholecystitis, 876, 876f
intracranial hemorrhage, 1257–1260, 1258f indeterminate potential morphology of, 876b
Ceruloplasmin, 83 Chlamydia trachomatis, 399–400, 400t, 988 Chronic diffuse interstitial (restrictive)
Cervical cancer, oral contraceptives in, 422 in conjunctival scarring, 1309 diseases, 688–700, 688t, 691b
Cervical carcinoma, 998–1000 Chlamydial infections, 381, 381b Chronic disease, anemia of, 658–659, 661b–
human papillomaviruses and, 992f, 998–999 Chloracne, 415 662b
screening and prevention for, 1000–1001, 1000f Chloroform, occupational health risks, 414– Chronic granulomatous disease, 241
Cervical intraepithelial neoplasia 415 Chronic GVHD, 239, 240f
(CIN), 997–998, 997b, 998f Chloroquine, 1230 Chronic hepatitis, 837, 838f
Cervical lymphoepithelial cyst, 745 Chokes, the, 132 Chronic illness, and malnutrition, 433
Cervicitis, acute and chronic, 995–996 Cholangiocarcinoma, 871f Chronic inflammation, 73, 96–101, 101b
Cervicovaginal smear, in cancer, 332f morphology of, 874b features of, 73t
Cervix, 995–1001 Cholecalciferol, 438–439 Chronic inflammatory demyelinating
endocervical polyps of, 996, 996f Cholecystitis, 875–876 poly(radiculo)neuropathy, 1221, 1221f
inflammations of, 995–996 Choledochal cysts, 859–860 Chronic kidney disease, 896–897, 897t
premalignant and malignant neoplasms of, 996– in gallbladder, 872 Chronic liver failure, 828
1000 Cholelithiasis, 873–875 Chronic lymphocytic leukemia
cervical carcinoma, 998–1000 obesity and, 448 (CLL), 595t, 597–599, 598f, 604b–605b
cervical intraepithelial neoplasia, 997– Cholestasis, 827, 854f, 855, 859b morphology of, 597b
998, 997t, 997b morphology of, 853b Chronic myelogenous leukemia
squamous intraepithelial lesions, 997– Cholesteatomas, 744–745 (CML), 622–624, 623f
998, 997b, 999t Cholesterol morphology of, 622b–623b
Cesarean section, 1031 intracellular accumulation of, 62–63 pathogenesis of, 623f
Cestodes, intestinal, and parasitic metabolism and transport of, 151–154 Chronic neuronal injury, 1242b
enterocolitis, 797 Cholesterol emboli, 130–131 Chronic nonspecific lymphadenitis, 589–590
CFH, Complement factor H Cholesterol esters, intracellular Chronic obstructive pulmonary disease
CFTR, Cystic fibrosis transmembrane accumulation of, 62–63 (COPD), 678–682, 682b
conductance regulator Cholesterol stones, 873t, 874f, 874b clinical features of, 681–682
CFUs, Colony-forming units Cholesterolosis, 63, 63f Chronic pancreatic injury, 886
Chagas disease, 393, 393b–394b Chondroblastic osteosarcoma, 1189b Chronic pelvic pain syndrome, 956
α chain, 198–199 Chondroma, 268 Chronic pericarditis, 578–579
β chain, 199 Chorioamnionitis, 458 Chronic rejection, 237b
Chalazion, 1307–1308 Choriocarcinoma Chronic renal failure, anemia due to, 661
Chalk stick-type fractures, 1183 gestational disorders, 1034–1035, 1035b Chronic tophaceous arthritis, 1205, 1205b
Chancroid, 367, 367b ovarian, 1025 Chronic traumatic encephalopathy
Channel proteins, 9 testicular, 972, 972f, 972b (CTE), 1252
Channelopathies, and sudden cardiac Choristoma, 269–270 Chronic vascular occlusion, 542–543
death, 554–555 Choroid, 1306f Chronic viral hepatitis, 837b–838b, 839f
Chaperone molecules, 13 Choroid plexus carcinomas, 1298 cirrhosis from, 828f
Charcot-Leyden crystals, 686b Choroid plexus papillomas, 1298 Chronic wound, 110
Charcot-Marie-Tooth (CMT) disease, 1224 Choroidal neovascularization, 1323–1324 Churg-Strauss syndrome, 515
CHD, Congenital heart disease Christmas disease, 669 Chvostek sign, in hypoparathyroidism, 1097
CHEK2, and breast cancer, 1049, 1049t Chromaffin, in adrenal medulla, 1126– Chylocele, 974
Chemical agents 1127, 1128b Chylothorax, 725
cell injury due to, 36 Chromatin, 3 Cigarette smoke, as teratogen, 456
toxicity of, 407–408 condensation, in apoptosis, 43f, 43b Cigarette smoking
Chemical organizing factors, 3 and atherosclerosis, 496
carcinogenesis, 321, 321f, 321t, 322b Chromium, as carcinogen, 280t and bladder cancer, 958
molecular targets of, 322 Chromophobe renal carcinoma, 950, 950b and cancer, 278
Chemical injury, inflammation due to, 74 Chromosomal disorder(s), 142, 164–173 and pancreatic carcinoma, 891, 893b
Chemokines chromosome 22q11.2 deletion syndrome, 169 Ciliary body, 1306f
in glomerular injury, 905 fetal growth restriction due to, 458 Ciliochoroidal effusion, 1328
in inflammation, 78, 90 hermaphroditism and CIN, Cervical intraepithelial neoplasia
Chemotaxis, of leukocytes, 79–80 pseudohermaphroditism, 173 Circulating proteins, 74
Cherry-red spot, in Tay-Sachs disease, 157b involving autosomes, 166–169, 170b Cirrhosis, 828, 829f
CHF, Congestive heart failure Klinefelter syndrome, 170–171 from chronic viral hepatitis, 828f
Chiari type I malformation, 1247 normal karyotype and, 164–165 hepatitis C-related, 870f
Chiari type II malformation, 1247–1248 prevalence of, 455–456 morphology of, 828b
Chickenpox, 355, 355f, 355b trisomy 21 (Down syndrome), 166–169 Citrullinated peptides (CCPs), 1200
Children Turner syndrome, 171–173, 172f Civatte bodies, 1158b
causes of death in, 453, 456t Chromosomal rearrangements, 166f CJD, Creutzfeldt-Jakob disease
congenital anomalies in, 453–457 Chromosome 22q11.2 deletion Class switching, 591
causes of, 455–457, 456t syndrome, 169 Classic KS, 520, 521b
pathogenesis of, 456–457, 457f Chromosomes, structural abnormalities Classical pathway, 90
diseases of, 453–483 of, 165–166 Clathrin, 11
inborn errors of metabolism in, 464–473 Chromothrypsis, in cancer, 318 Clathrin-coated pits, 11
mortality, in Global Burden of Disease, 405 Chronic antibody-mediated rejection, 236– CLC1, mutations of, 1236
tumors and tumor-like lesions in, 475–483 237 Clear cell carcinoma
in kidney, 949, 949f, 950b ischemic bowel disease of, 781–783, 781b–782b cyanotic, 538
of ovaries, 1021–1022 Colon cancer, 449 etiology and pathogenesis of, 535–536
Clear cell chondrosarcoma, 1192b Colon carcinoma, 275f incidence of, 534–535, 535t
Cleft lip, 454f Colonic polyp, 268f with left-to-right shunts, 536–538, 538f
Cleft palate, 454f Colony-forming units (CFUs), 584, 585f atrial septal defects, 536–537, 538f
Cleidocranial dysplasia, 1175, 1176t Colony-stimulating factors (CSFs), 102, 200 patent ductus arteriosus, 538, 538f
Climate change, health effects of, 406– Colostrum, 1037–1038 patent foramen ovale, 537
407, 406f Comedo ductal carcinoma in situ, 1053b– ventricular septal defects, 537–538, 538f–539f
CLL, Chronic lymphocytic leukemia 1054b, 1054f obstructive, 540–541
Clonal hematopoiesis of indeterminate Communicating hydrocephalus, 1244 aortic stenosis and atresia, 541
potential (CHIP), 494–495 Communicating junctions, 13 coarctation of the aorta, 540–541, 540f
Clonal selection, 193–194 Complement, in glomerular injury, 905 pulmonary stenosis or atresia, 541
Close-up, of cortical surface in benign Complement cascade, in septic shock, 135– with right-to-left shunts, 536, 538–540, 539f
nephrosclerosis, 935f 136 persistent truncus arteriosus, 538
Clostridial cellulitis, 380b–381b Complement factor H (CFH), 92 tetralogy of Fallot, 538–539, 539f
Clostridial infections, 380, 380b–381b Complement pathway, alternative, in total anomalous pulmonary venous connection, 538
Clostridium perfringens, 380, 380f membranoproliferative transposition of the great arteries, 539–540, 539f–
Clotting, in inflammation, 92 glomerulonephritis, 904 540f
Clotting factor, abnormalities in, 667– Complement system, 90–92 tricuspid atresia, 538
669, 667f activation and function of, 91f Congenital hepatic fibrosis, 860, 860f
CLRs, C-type lectin receptors deficiencies affecting, 241–242 Congenital hypothyroidism, 1077
CML, Chronic myelogenous leukemia in innate immunity, 191 Congenital infections, with
CMV, Cytomegalovirus Complex chromosomal rearrangements, 318 cytomegalovirus, 356
CNS, Central nervous system Complex karyotype, 1208–1209 Congenital lactase deficiency, 786
CNV, Copy number variations Complex multigenic disorders, 142, 163– Congenital melanosis oculi, 1310
Coagulation 164 Congenital myasthenic syndromes, 1226
disseminated intravascular, 118, 130, 669–671 Complex sclerosing lesion, of Congenital nevus, 1136t
in septic shock, 136–137 breast, 1043b, 1044f Congenital syphilis, 376–377, 377b–378b
factors that limit, 122–123 Compound heterozygosity, 638 Congestion, 117–118
in inflammation, 92 Compression atelectasis, 675 edema due to, 117–118
Coagulation cascade, in hemostasis, 120– Compression neuropathy, 1224 morphology of, 118b
123, 121f Concussion, 1249 Congestive heart failure (CHF), 530
Coagulation factors, 123b Conduction system, of heart, 528 edema due to, 116
Coagulation system, in glomerular Condyloma acuminatum, 1167b–1168b therapy for, 534
injury, 905 of penis, 964, 964f, 964b Congestive hepatomegaly, in right-sided
Coagulative necrosis, 40f, 40b–41b of vulva, 991, 991f heart failure, 533b
Coagulopathy, consumptive, 130 Condylomata lata, in syphilis, 376 Congestive splenomegaly, 630
Coal dust Confluent necrosis, in hepatocytes, 825 morphology of, 630b
intracellular accumulation of, 64 Congenital abnormalities, of gastrointestinal in right-sided heart failure, 533b
lung diseases due to, 692t tract, 754–756, 756b–757b Conidia, 383
pneumoconioses due to, 415 atresia, fistulae, and duplications, 754f Conjugated hyperbilirubinemia, 853t
Coal workers' diaphragmatic hernia, omphalocele, and Conjunctiva, 1306f, 1308–1309, 1309b
pneumoconiosis, 64, 692, 692b– gastroschisis, 754 Conn syndrome, 1119
693b, 693f ectopia, 755 Connective tissue, remodeling of, 106–108
Coarctation of the aorta, 540f Hirschsprung disease, 755–756, 756f, 756b Connective tissue deposition, 103, 107
Cocaine, abuse of, 423–424, 425f Meckel diverticulum, 755, 755f repair by, 105–108
Coccidioides immitis, 713 pyloric stenosis, 755 Connective tissue diseases, 221
Codominance, 144 Congenital adrenal hyperplasia, 1120– Connexins, 13
Cofactor, 121–122 1121, 1121b Connexons, 13
Cognitive impairment, in Alzheimer Congenital aganglionic megacolon, 755– Contact dermatitis, 214
disease, 1277 756, 756f, 756b Contact sensitivity, 213t
Co-infection, in HDV, 835 Congenital anomalies, 453–457 Contractile dysfunction, due to myocardial
COL7A1 gene, in epidermolysis of bladder, 955, 955f infarction, 551
bullosa, 1164 causes of, 455–457, 456t Contraction, in tissue repair, 111
Cold agglutinin type immunohemolytic of kidney, 940–941 Contraction atelectasis, 675
anemia, 649t, 650 agenesis, 940 Contraction band necrosis, 517
Cold hemolysin type immunohemolytic ectopic kidneys, 940–941 Contraction bands, after myocardial
anemia, 649t, 650 horseshoe kidneys, 941 infarction, 550
Cold sores, 354b–355b hypoplasia, 940 Contrecoup injury, 1249
Collagen biosynthetic pathway, 25f pathogenesis of, 456–457, 457f Contusions, of brain, 1249, 1250f, 1250b
Collagen vascular diseases, 221 of penis, 963 Coombs antiglobulin test, 649
Collagens, extracellular matrix and, 23 of testes, 966–967, 967f COPD, Chronic obstructive pulmonary
Collar-button lesion, 723b of ureters, 954, 954t disease
Collecting duct carcinoma, 950, 950b Congenital contractural Copper, deficiency of, 1223
Collectins, 74 arachnodactyly, 148–149 Copy number high/serous-like tumors, 1008
Colloid carcinoma Congenital fiber type disproportion, 1231t Copy number low/MSS (microsatellite
of breast, 1056b–1058b, 1059f Congenital heart disease (CHD), 534– stable) tumors, 1008
of prostate, 982 541, 541b–542b Copy number variations (CNV), 183
Colon cardiac development and, 534, 537f Cor pulmonale, 533, 556, 556b–557b
angiodysplasia of, 783 clinical features of, 536 disorders predisposing to, 556t
due to pulmonary embolism, 131 CTLA-4, in anergy, 217 Cystic fibrosis transmembrane conductance
Coreceptors, 195 C-type lectin receptors (CLRs), 192 regulator (CFTR), 467f–468f
Cornea, 1306f, 1310–1312 Curare, 1226 dysfunction, 681
Corneal stroma, 1310–1311 Curie (Ci), as radiation unit, 429 in pancreatitis, 884t
Corneal ulcer, 438f Curschmann spirals, 686b Cystic follicles, 1016
Coronary arterial occlusion, and myocardial Cushing syndrome, 1072, 1118f, 1118b Cystic hygromas, 463, 464f, 520
infarction, 544 clinical course of, 1117–1118 Cystic medial degeneration, 505–
Coronary artery disease, obesity and, 448 clinical features of, 1118t 506, 505f, 507b–508b
Coronary atherosclerosis, 553b due to cancer, 328 Cystic neoplasms, of pancreas, 888–890
Coronary syndromes, acute, 543 endogenous causes of, 1116t Cysticerci, 396f, 396b
Corpora amylacea, 1243 morphology of, 1116b–1117b Cystine stones, 947, 947t
Corpus callosum, agenesis of, 1247, 1247f Cutaneous anthrax, 363 Cystitis
Cortical atrophy, in Alzheimer Cutaneous leishmaniasis, 392b acute and chronic, 955–956
disease, 1278f, 1278b Cutaneous T-cell lymphoma cystica, 957
Cortical hamartomas, in tuberous (CTCL), 1151, 1152f eosinophilic, 955b–956b
sclerosis, 1302b Cutoffs, 407 glandularis, 957
Cortical inclusion cysts, of CX3C chemokines, 90 hemorrhagic, 955b–956b
ovaries, 1018, 1018f C-X-C chemokines, 90 interstitial, 956
Corticobasal degeneration (CBD), 1284 Cyanide, poisoning, 56–57 with malacoplakia, 956, 956f, 956b
Corticosteroids, for inflammation, 88 Cyanosis, 117–118 morphology of, 955b–956b
Corticotroph, 1068t Cyanotic congenital heart disease, 538 pathogenesis of, 955b–956b
Corticotroph adenomas, 1071–1072 Cyclin D1 gene polypoid, 956–957
morphology of, 1071b–1072b in parathyroidism, 1094 radiation, 955b–956b
Corticotroph cell hyperplasia, 1115 in pituitary tumors, 1069t tuberculous, 955
Corticotropin, 328 Cyclin-dependent kinases (CDKs), 25 Cystocele, 953
Corynebacterium diphtheriae, 361–362 in cell cycle, 290 Cystosarcoma phyllodes, 1062
Costimulators, in immune responses, 200 oncogenes for, 290 Cytochrome c, in apoptosis, 44–45
Cotinine, 417–418 role of, 27f Cytochrome P-450 enzyme system, 408
Cotton, asthma due to, 692t Cyclins, 25 alcohol on, 420b
“Cotton-wool spots,”, 1320, 1321f oncogenes for, 290 Cytochrome P-450-dependent mono-
Coumadin, 121–122 role of, 27f oxygenases, 322
Councilman bodies, 825 Cyclooxygenase (COX), in Cytogenetic disorder(s)
Counter-inflammatory responses, in septic inflammation, 86 chromosome 22q11.2 deletion syndrome, 169
shock, 135–136 Cyclooxygenase (COX) inhibitors, hermaphroditism and
Coup injury, 1249 mechanism of action of, 88 pseudohermaphroditism, 173
Cowden syndrome, 1148t Cyclooxygenase 1 (COX-1), in involving autosomes, 166–169, 170b
PTEN in, 298–299 inflammation, 86 involving sex chromosomes, 170–173, 173b
Craniopharyngioma, 1074, 1074b Cyclooxygenase 2 (COX-2), in Klinefelter syndrome, 170–171
Craniosynostosis, 1174 inflammation, 86 terminology, 165
Craniotabes, 440b–442b Cyclophosphamide, and bladder cancer, 958 trisomy 21 (Down syndrome), 166–169
C-reactive protein (CRP), 102 Cylindroma, 1144, 1144f, 1144b–1145b Turner syndrome, 171–173, 172f
and atherosclerosis, 496, 496f CYP2E1, in alcohol metabolism, 419 Cytogenomic array technology, 183–184
Creatine kinase, in myocardial Cyst(s) Cytokines, 199–200
infarction, 550 breast, 1042f, 1042b in glomerular injury, 905
Creeping substitution, 1185b apocrine, 1042f, 1042b in immediate hypersensitivity, 207
Crescentic glomerulonephritis, 907t, 909– blue-dome, 1042f, 1042b in inflammation, 78, 89f, 89t, 90
911, 909t, 910f, 910b dermoid, of skin, 1144b–1145b Cytokine-mediated cell death, 1079
Cretinism, 1078 pilar (trichilemmal), 1144b–1145b Cytokine T lymphocyte-mediated
Creutzfeldt-Jakob disease (CJD), 1274 thyroglossal duct, 1092 apoptosis, 42–43
Crewcut, 647f Cystadenocarcinomas, ovarian, 1017 Cytologic methods, for diagnosis of
Crigler-Najjar syndrome, type I and II, 853t Cystadenofibroma, 1022 cancer, 331–332
Crohn disease, 101 Cystadenomas, 268 Cytologic smears, for cancer, 331
Crooke hyaline change, 1116b–1117b Cystic diseases, of kidney, 941– Cytomegalic inclusion disease, 356
CRP, C-reactive protein 945, 941t, 945b Cytomegalovirus (CMV), 356–357, 356f
Cryoglobulinemia, essential mixed, acquired, 941t, 945 in AIDS, 256
glomerular lesions in, 924 autosomal dominant (adult) polycystic, 941– congenital infections with, 356
Cryptococcal meningitis, 1268 943, 941f–943f, 941t, 942b encephalitis due to, 1265f, 1266b
Cryptococcosis, 385–386, 385b autosomal recessive (childhood) in immunosuppressed individuals, 357
in AIDS, 256 polycystic, 941f, 941t, 943–944, 943b mononucleosis, 356–357
Cryptococcus neoformans, 385, 386f medullary sponge kidney, 941f, 941t, 944 morphology of, 356b
Cryptogenic cirrhosis, 828 nephronophthisis, 944, 944f, 944b perinatal infections, 356
Cryptogenic fibrosing alveolitis, 688–689 and adult-onset medullary, 941t
Cryptorchidism, 966–967, 966b, 967f simple cysts, 941f, 941t, 945
Cryptosporidium, and parasitic Cystic fibrosis, 466–473 Cytopathic-cytoproliferative
enterocolitis, 797–798 clinical features of, 472–473, 472t reaction, 348, 348f
Crystals, 1206b environmental modifiers of, 470–473 Cytoplasmic blebs, in apoptosis, 43f, 43b
CSF, Cerebrospinal fluid genetic modifiers of, 470–473 Cytoskeletal abnormalities, cell injury due
CSFs, Colony-stimulating factors malabsorption and diarrhea in, 784 to, 51
CTCL, Cutaneous T-cell lymphoma morphology of, 471b Cytoskeletal proteins, accumulation of, 64
CTE, Chronic traumatic encephalopathy Cytoskeleton, 11–12, 11f
Cytotoxic edema, 1244 Deposition of amyloid, 1113b development of, 1104f
Cytotoxic T lymphocyte-associated antigen- Dermal papillae, 1163b pathogenesis of, 1103–1105
4 (CTLA4) gene, 219t, 1078–1079 Dermatitis, herpetiformis, 1163, 1164b– Diabetic ketoacidosis, 1106
1165b Diabetic macrovascular
Dermatofibroma, 1149, 1150f, 1151b disease, 1107, 1108b–1109b
Dermatofibrosarcoma protuberans, 1150– Diabetic microangiopathy, 1108b–1109b
D 1151, 1151f, 1151b Diabetic microvascular disease, 1107
DAD, Diffuse alveolar damage Dermatographism, 1152 Diabetic nephropathy, 923, 1108b–
DAF, Decay accelerating factor Dermatomyositis, 1228–1229, 1229f 1109b, 1111
Damage-associated molecular patterns morphology of, 1228b Diabetic neuropathy, 1108b–1109b
(DAMPs), 135–136 Dermatophytes, 340 Diabetic ocular complications, 1108b–1109b
in innate immunity, 191 Dermatophytoses, 1169b Diabetic retinopathy, 1108b–1109b
DAMPs, Damage-associated molecular Dermatosis(es), inflammatory Diabetic ulcers, 110, 111f
patterns acute, 1153–1156 Diapedesis, of leukocyte through
Dandy-Walker malformation, 1247 eczematous dermatitis, 1154–1155 endothelium, 78–79
Darier sign, 1152 erythema multiforme, 1156 Diaphragmatic hernia, 754
D-binding protein (DBP), 439 urticaria, 1153–1154 Diarrhea, 783–787
DBP, D-binding protein chronic, 1157–1158 exudative, 784
DCIS, Ductal carcinoma in situ lichen planus, 1158 malabsorptive, 784
D-dimers, 122–123 psoriasis, 1157 osmotic, 784
DDT, Dichlorodiphenyltrichloroethane seborrheic dermatitis, 1158 secretory, 784
De Quervain thyroiditis, 1080 Dermatosis papulosa nigra, 1142 Diastolic dysfunction, 530
Death domains, 45–46 Dermis, tumors of, 1149–1151 Diastolic failure, 533
Death receptor-initiated pathway, of Dermoid cysts DIC, Disseminated intravascular coagulation
apoptosis, 45–46, 46f ovarian, 1023, 1023f Dichlorodiphenyltrichloroethane
Death receptors, 45 of skin, 1144b–1145b (DDT), 415
Decay accelerating factor (DAF), in DES, Diethylstilbestrol Diet
complement system, 91–92 Descemet membrane, 1306f, 1311 and atherosclerosis, 450
Decompression sickness, 132 Desmoid tumors, 1211 and cancer, 278, 449
Dedifferentiated chondrosarcoma, 1192b Desmoids, 111 Dietary insufficiency, 433
Deep fibromatosis, 1211 Desmoplasia, 268 Diethylstilbestrol (DES), developmental
Deep venous thrombosis (DVT), 130 Desmosomes, 12–13 anomalies of vagina, 994
edema due to, 116 Developmental aneurysms, 487 Dieulafoy lesion, 766
pulmonary embolism due to, 131, 131f DHT, Dihydrotestosterone Differentiation, in neoplasia, 270–273, 276t
Defective imprinting, 179 Diabetes Differentiation therapy, 317
Defensins, in phagocytosis, 83 acute metabolic complications of, 1106–1107 Diffuse alveolar damage (DAD), 676, 677f
Deficiency syndromes chronic, manifestations of, 1111–1112 Diffuse axonal injury, 1250, 1250b
function and, of vitamins, 443t chronic complications of, 1107–1108, 1108b– Diffuse cortical necrosis, 939f, 939b
trace elements and, 444t 1109b Diffuse cutaneous leishmaniasis, 392b
Deformations, 454–455 classic triad of, 1106 Diffuse esophageal spasm, 757
Degenerative joint disease, 1198 clinical features of, 1106–1112, 1107f Diffuse hyperplasia, in adrenal
7-Dehydrocholesterol, 438–439, 439f long-term complications of, 1109f glands, 1116b–1117b, 1117f
Delayed union, 1185 monogenic forms of, 1105 Diffuse large B-cell lymphoma
Delayed-type hypersensitivity peripheral neuropathy in, 1222, 1223f (DLBCL), 595t, 600–601, 600f–
(DTH), 212, 214f morphology of, 1223b 601f, 604b–605b
chronic inflammation due to, 96 and pregnancy, 1105 morphology of, 600b–601b
Deletions, 165, 166f tissue repair and, 108 Diffuse lupus nephritis, 225b–228b
in cancer, 317 type 1, 1099 Diffuse mesangial sclerosis, 1108b–1109b
in immunologic tolerance, 216 HLA alleles and, 219t Diffuse microvesicular steatosis, 826b
Dementia type 2, 1099 Diffuse neurofibromas, 1237, 1237b–1238b
with Lewy bodies, 1283–1284 Diabetes-induced hyperglycemia, 1108b– Diffuse plaques, in Alzheimer
pugilistica, 1252 1109b disease, 1278b
Demyelinating diseases, 1269–1273 Diabetes insipidus, 1073–1074 Diffuse sclerosing variant, 1088b–1089b
central pontine myelinolysis, 1272–1273 Diabetes mellitus, 1097–1112 DiGeorge syndrome, 169, 169f, 244, 631
encephalomyelitis and atherosclerosis, 496 in hypoparathyroidism, 1097
acute disseminated, 1272 classification of, 1099–1100, 1099t Dihydrotestosterone (DHT), in benign
acute necrotizing hemorrhagic, 1272 diagnosis of, 1098–1099 prostatic hyperplasia, 976, 976f
multiple sclerosis, 1269–1272, 1271f–1272f environmental factors of, 1102 1,25-Dihydroxyvitamin D [1a,
neuromyelitis optica, 1272 genetic susceptibility, 1101–1102 25(OH)2D3], 439–440, 439f
Demyelinating neuropathies, 1220 glucose homeostasis, 1100–1101 Dilated cardiomyopathy, 568–572, 569f–
Dendritic cell(s) maternal, congenital anomalies due to, 456 571f, 571b
cell-mediated immunity, 201f, 203b–204b pancreatic neuroendocrine tumors, 1113–1114 Dimorphic fungi, 383
in immune response, 196, 201f pathogenesis and long-term complications Dioxin (TCDD; 2,3,7,8-tetrachlorodibenzo-
of skin, 1133–1134 of, 1112b–1113b p-dioxin), 415
Denervation atrophy, 59–60 in retinal vascular disease, 1321f–1322f Dipeptidyl peptidase (DPPs), 1100–1101
Dengue, 353 type 1, 213t Diphtheria, 361–362, 362f, 362b
Dense (δ) granules, 119–120 pathogenesis of, 1101–1103 peripheral neuropathy in, 1222
Dense deposit disease, 907t, 918–920, 919f– stages in development of, 1103f Direct Coombs antiglobulin test, 649
920f, 920b vs. type 2, 1100t Direct Coombs test, 222t
Dentigerous cyst, 737 type 2 Direct parenchymal injury, 1249
Discoid rash, in systemic lupus DSBs, Double stranded breaks dependent, 117b
erythematosus, 222t DTH, Delayed-type hypersensitivity in inflammation, 75, 80f
Disruptions, 454, 454f DUB, Dysfunctional uterine bleeding morphology of, 117b
Dissecting osteitis, 1181f, 1181b Dubin-Johnson syndrome, 853t pathophysiologic features of, 116t
Disseminated intravascular coagulation Duchenne muscular dystrophy, 1232, 1233f periorbital, 117b
(DIC), 118, 130, 669–671, 671b morphology of, 1232b–1233b pitting, 117b
due to cancer, 330 Duct ectasia, 1041, 1041f, 1041b pulmonary, 117b, 533, 675–676, 675t
morphology of, 670b Duct of Santorini, 881, 882f caused by microvascular (alveolar) injury, 676
pathophysiology of, 670f Duct of Wirsung, 881, 882f hemodynamic, 675
in septic shock, 136–137 Ductal carcinoma in situ noncardiogenic, 676
Disseminated peritoneal (DCIS), 1053, 1053b–1054b, 1054f– subcutaneous, 117b
leiomyomatosis, 1014b 1055f systemic, mechanisms of, 117f
Dissolution, of thrombi, 129 Ductal hyperplasia, atypical, 1045, 1045f tissue, in right-sided heart failure, 533b
Distal symmetric diabetic Ductular cholestasis, 855f Edema factor (EF), in anthrax, 363
polyneuropathy, 1223 Ductus arteriosus, patent, 538, 538f EDS, Ehlers-Danlos syndromes
Disuse, atrophy of, 59 coarctation of the aorta with, 540–541, 540f Edwards syndrome, 168f, 169
Divalent metal transporter 1 Duncan disease, 358 EF, Edema factor
(DMT1), 656, 657f Duodenal ulcers, 94f Effusions, 93, 115–117
Diverticulum(a), Meckel, 755, 755f Dupuytren contracture, 1211 EGF, Epidermal growth factor
DLBCL, Diffuse large B-cell lymphoma Duret hemorrhages, 1245, 1245f Ehlers-Danlos syndromes (EDS), 149–
DMT1, Divalent metal transporter 1 DVT, Deep venous thrombosis 151, 150t, 151b
DNA-anti-DNA complexes, 225 Dysembryoplastic neuroepithelial bleeding disorder due to, 663
DNA damage tumor, 1298 Ehrlichiosis, 381–382
apoptosis due to, 42 Dysfunctional uterine bleeding Eicosanoids, in inflammation, 86, 88
cell injury due to, 51 (DUB), 1002–1004, 1003f, 1003t Eisenmenger syndrome, 536
in cellular aging, 67, 67f Dysgerminoma Elastic arteries, 486
due to ionizing radiation, 429 ovarian, 1024–1025, 1025f, 1025b Elastin, extracellular matrix and, 23
DNA methylation, 3 testicular, 970 Electromechanical dissociation, 701–702
in cancer, 319 Dyskeratosis, 1135t Electron-dense deposits, subendothelial, 918
DNA microarrays, 333 Dyslipoproteinemias, in atherosclerosis, 498 Elephantiasis, 398b–399b, 399f
DNA mismatch repair, 314 Dysostoses, of bone, 1174 edema due to, 116–117
DNA polymerase, 315 Dysphagia, in systemic sclerosis, 233 Embolism, 130–132, 133b
DNA polymorphisms, 184f Dysplasia, 272–273, 455 air, 132
Döhle bodies, 588, 588f of bone, 1174 amniotic fluid, 132, 133f
Dolor, 73, 95–96 Dysplastic nevi, 1136t, 1137–1138, 1138f– cerebral infarction due to, 1253–1254
Dormancy, of metastasis, 309 1139f, 1138b–1139b fat and marrow, 131–132, 132f
Double minutes, in cancer, 317–318 Dysplastic nevus syndrome, 1137–1138 paradoxical, 131, 536, 544
Double stranded breaks (DSBs), 432 Dysplastic nodules, in liver, 869b–870b pulmonary, 131
Down-regulation Dyspnea, 678 systemic, 131
of BMPR2, 703 in left-sided heart failure, 532–533 Embolization, of thrombi, 129
of growth, 458 paroxysmal nocturnal, 532–533 Embolus(i), 130–131, 131f
of GSTP1 expression, 979 Dystrophic calcification, 65–66, 66f, 1074b cholesterol, 130–131
Downstream phosphorylation, 18–19 Dystrophin, 1232, 1232f coronary artery occlusion due to, 544
DPPs, Dipeptidyl peptidase Dystrophinopathies, 1232 paradoxical, 544
Dressler syndrome, 552 saddle, 131
Driver mutations, in cancer, 282 small, 701–702
Drug(s) Embryonal carcinoma, testicular, 971, 971f–
cell injury due to, 36 E 972f, 971b
congenital anomalies due to, 456 E6 proteins, oncogenic activities of, 324– Embryonal neoplasms, 1298–1299
genetically determined adverse reactions to, 148 325 Embryonal
Drug abuse, 423–426, 424t E7 proteins, oncogenic activities rhabdomyosarcoma, 1212f, 1212b
of 3,4 methylenedioxymethamphetamine of, 324f, 325 of bladder, 962
(MMDA), 426 Early endosome, 11 of vagina, 995, 995f
of amphetamines, 425 Ears, disorders of, 744–745, 745b Embryonic stem cells, 28, 29f
of cocaine, 423–424, 425f Eating disorders, 435 Embryopathy
of marijuana, 425–426 EBNA-2 gene, 325 diabetic, 456
of methamphetamine, 425 EBV, Epstein-Barr virus retinoic acid, 457
of opiates, 424–425 E-cadherin, 12, 297–298 valproic acid, 457
Drug-eluting stents, 523 in invasive lobular carcinoma, 1055 EMD, Emery-Dreifuss muscular dystrophy
Drug hypersensitivity vasculitis, 510 in metastasis, 307 Emerging infectious diseases, 400–401, 401t
Drug-induced interstitial nephritis, 932– Ecchymoses, 125 Emery-Dreifuss muscular dystrophy
933, 932f Eccrine poroma, 1144 (EMD), 1234
Drug-induced liver injury, 841–842, 842b Eclampsia, 864, 864f Emphysema, 678t, 679–681, 681b, 682t
patterns of injury in, 841t ECM, Extracellular matrix bullous, 682, 683f
Drug-induced lupus erythematosus, 229 ECs, Endothelial cell(s) centriacinar (centrilobular), 679, 679f–680f
Drug-induced thrombocytopenia, 665 Ecthyma gangrenosum, 366b compensatory hyperinflation, 682
Drug injury, 426b Ectopia lentis, in Marfan syndrome, 149b distal acinar (paraseptal), 679
Drug reactions, bleeding disorder due Ectopic pregnancy, 1029–1030 forms of, 682–683
to, 663 Edema, 115–117, 116f, 117b interstitial, 682–683
Drug toxicity, agranulocytosis and, 586–587 clinical features of, 117 irregular, 680
obstructive overinflation, 682 Endometrial cancer, oral contraceptives antithrombotic properties of, 123–124
panacinar (panlobular), 679, 679f–680f in, 422 corneal, 1311
pathogenesis of, 680–681, 680f Endometrial carcinoma, 1007, 1010b– fibrinolytic effects of, 124
Empty sella syndrome, 1073 1011b, 1013b in hemostasis, 123–124
Empyema, 725 type I, 1008t, 1009, 1010f leukocyte adhesion to, 77–78
EMT, Epithelial-to-mesenchymal transition type II, 1008t, 1011f, 1013b platelet inhibitory effects of, 123
Encephalitis, mumps, 351b Endometrial hyperplasia, 59, 1006– Endotoxin, bacterial, 346–347
Encephalocele, 1246 1008, 1007f, 1007b–1008b Endovascular stenting, 523
Enchondromas, 1190, 1191f, 1191b Endometrial intraepithelial End-stage liver disease, 858
End product, decreased amount of, 148 neoplasia, 1007b–1008b Energy balance, regulation of, 444–
Endemic African KS, 520–521 Endometrial polyps, 1006 445, 445f–446f
Endemic goiter, 1083 Endometrial stroma, tumors of, 1013– Engulfment, in phagocytosis, 80–81, 82f
Endocarditis 1014, 1015b eNOS, Endothelial nitric oxide synthase
infective, morphology of, 128b–129b Endometrioid Entamoeba histolytica, and parasitic
Libman-Sacks, 128b–129b adenocarcinomas, 1010f, 1010b–1011b enterocolitis, 797
nonbacterial, thrombotic, 128b–129b Endometrioid adenofibromas, 1021 Enteroaggregative Escherichia coli, 793
of systemic lupus erythematosus, 565 Endometrioid carcinoma, 1007, 1010b– Enterobius gregorii, and parasitic
Endocervical polyps, 996, 996f 1011b, 1021, 1021b enterocolitis, 796–797
Endochondral ossification, 1173 Endometrioid endometrial carcinoma, 1008– Enterobius vermicularis, and parasitic
Endocrine atypia, 1094b–1095b 1010 enterocolitis, 796–797
Endocrine disorders Endometrioid tumors, ovarian, 1021, 1021b Enterochromaffin cells, 1097
of adrenal cortex, 1115–1126 Endometriosis, 1004–1006, 1004f– Enterococcal infections, 360–361, 360b
cretinism, 1078 1005f, 1006b Enterocolitis
of pancreas, 1097–1114 Endometriotic lesions bleed, 1006b infectious, 787–798, 788t
diabetes mellitus, 1097–1112 Endometritis due to Campylobacter, 789–790, 789b, 790f
of parathyroid glands, 1093–1097 acute, 1004 due to cholera, 787–789, 789f
hyperparathyroidism, 1093–1096 chronic, 1004 due to Escherichia coli, 792–793
of pineal gland, 1130–1131 Endometrium, 1001–1016 due to salmonellosis, 791, 791b
of pituitary gland adenosarcomas, 1013 due to shigellosis, 790–791, 790b
carcinoma, 1072 carcinoma of, 1008 due to typhoid fever, 791–792
gonadotroph (LH-producing and FSH-producing) dating of, 1001 due to Whipple disease, 794, 794f, 794b
adenomas, 1072 endometriosis and adenomyosis, 1004– due to Yersinia, 792, 792b
nonfunctioning (silent variants, null-cell) 1006, 1004f, 1006b parasitic, 795–798
adenomas, 1072 functional endometrial disorders (dysfunctional pseudomembranous, 793, 793f, 793b
pituitary adenomas and hyperpituitarism, 1067– uterine bleeding), 1002– viral, 794–795, 796f
1072 1004, 1003f, 1003t necrotizing, 460–461, 461f, 461b, 782–783
prolactinomas, 1070f histology in the menstrual cycle, 1001– radiation, 782
thyrotroph (TSH-producing), 1072 1002, 1002f Enterohemorrhagic Escherichia coli, 792–
of thyroid gland, 1075–1092 malignant mixed Müllerian 793
goiter, 1082–1084 tumors, 1012, 1012b, 1013f Enteroinvasive Escherichia coli, 793
Graves disease, 1081–1082, 1082f malignant tumors of, 1008–1012 Enteropathogenic Escherichia coli, 792
hyperthyroidism, 1075–1077 stromal tumors, 1012b, 1013–1014 Enterotoxigenic Escherichia coli, 792
hypothyroidism, 1077–1078 Endoneurium, 1218 Environment, definition of, 405
thyroiditis, 1078–1081 Endophthalmitis, 1314–1315 Environmental carcinogens, 278
Endocrine neoplasm Endoplasmic reticulum (ER), 13 Environmental diseases, 405–451
of adrenal cortex, 1115–1126 Endothelial activation, 88– alcohol, effects of, 418–420
pancreatic neuroendocrine, 1113–1114, 1114f 89, 488, 488f, 676 climate change and, 406–407, 406f
α-cell tumors (glucagonomas), 1114 in septic shock, 136 health effects of, 406–407, 406f
hyperinsulinism, 1113–1114 Endothelial and leukocyte adhesion definition of, 405
VIPoma, 1114 molecules, 78t due to thermal injury, 427–428
Endocrine signaling, 17 Endothelial cell(s) (ECs) electrical injury, due to, 428
Endocrine stimulation, loss of, atrophy due contraction of, in inflammation, 76 ionizing radiation, injury produced by, 428–
to, 60 properties and functions of, 488t 433, 430b–431b
Endocrine system, 1065–1132 vascular, in response to injury, 488 occupational health risks, due to, 414–418, 414t
adrenal glands, 1114–1129 in vascular wall response to injury, 487 pollution, due to, 408–414, 410b
adrenal medulla in, 1126–1129 Endothelial dysfunction, 488, 1108b–1109b air, 408–410
feedback inhibition in, 1065–1066 Endothelial injury metals, 411–414
multiple endocrine neoplasia syndromes, 1129– in atherosclerosis, 497–498 therapeutic drugs and drugs of abuse, injury
1130 disseminated intravascular coagulation due by, 420–426
pancreas, 1097–1114, 1108b–1109b to, 669 tobacco, effects of, 415–418, 416f, 416t
parathyroid glands in, 1093–1097 in inflammation, 76 toxicity of chemical and physical agents, due
pineal gland, 1130–1131 in septic shock, 136 to, 407–408, 407f–408f
pituitary gland, 1066–1074 in thrombosis, 126 Environmental hazards, toxicity of, 407
thyroid gland, 1075–1092 in thrombotic microangiopathies, 937 Environmental influences, of congenital
Endocrine tumors, 1129 Endothelial nitric oxide synthase (eNOS), 83 anomalies, 456
Endocrinopathies, paraneoplastic syndromes Endothelial protein C receptor, 123–124 Environmental toxins, and breast
and, 328 Endothelin, in hemostasis, 118 cancer, 1046–1047
Endodermal sinus tumor, testicular, 971 Endothelium Enzyme defects, 148
Endogenous pyrogens, 101–102 anticoagulant activities of, 124f disorders associated with, 154–162
anticoagulant effects of, 123–124 Enzymes, 1176–1178
in immediate hypersensitivity, 207 Erythema nodosum, 1166b Exotoxins, bacterial, 347
Eosinophil(s) Erythroblastosis fetalis, 463b–464b, 464f Exstrophy, of bladder, 955, 955f
in chronic inflammation, 99–100, 100f Erythrocyte sedimentation rate, 102 External elastic lamina, of blood
in immediate hypersensitivity, 207–208 Erythroid precursors, in hemolytic vessels, 486
Eosinophilia, in inflammation, 102 anemia, 638f, 638b External herniation, 780
Eosinophilic cystitis, 955b–956b Erythromelalgia, 625 Extra-adrenal paragangliomas, familial
Eotaxin, 90 Erythroplakia, of oral cavity, 734–735, 735f syndromes associated with, 1127t
Ependymal cells, 1243 Erythropoiesis, anemias of Extracellular matrix (ECM)
Ependymoma, 1296–1298, 1296b– diminished, 636t, 651–661 components of, 23–25, 23f–24f
1298b, 1297f aplastic, 659–661, 659t, 660f interaction with, 21–25, 22f
Ephelis, 1135 of chronic disease, 658–659 invasion of, in metastasis, 307–308
Epicardial coronary arteries, 528 due to chronic renal failure, 661 Extracellular microbes, elimination of, 201–
Epidemic typhus, 381 due to hepatocellular liver disease, 661 203
Epidermal appendages, disorders of, 1165 due to pure red cell aplasia, 661 Extradural abscess, 1263
acne vulgaris, 1165 of folate deficiency, 651t, 654–655 Extralobar sequestration, 674
rosacea, 1165 iron deficiency, 655–658, 655t, 657f Extramedullary plasmacytoma, 611b
Epidermal growth factor (EGF), 20, 20t megaloblastic, 651–654, 651f–652f, 651t Extranodal NK/T-cell
Epidermal maturation, disorders of, 1152– myelophthisic, 661 lymphoma, 595t, 607, 607b
1153 pernicious (vitamin B12 deficiency), 651t, 652– Extrauterine stem/progenitor cell theory, of
Epidermal tumors, premalignant and 653 endometriosis, 1005
malignant, 1145–1148 Escherichia coli, in pyogenic Extravascular hemolysis, 637
actinic keratosis, 1145–1146 osteomyelitis, 1185–1186 in β-thalassemia, 645
basal cell carcinoma, of skin, 1147–1148 E-selectin, in inflammation, 78, 78t “Extrinsic allergic alveolitis,”, 698
squamous cell carcinoma, 1146–1147 Esophageal atresia, 754, 754f Exudate(s), 75
Epidermodysplasia verruciformis, 1146 Esophageal lacerations, 758, 758t fibrinous, 93–94, 93f
Epidermolysis bullosa, 1163–1164, 1164f Esophageal mucosal webs, 757 formation of, 75f
Epididymis, inflammation of, 967–968, 968f Esophageal obstruction, 757 Exudation, 75
Epididymitis, nonspecific, 967, 967b– eosinophilic, 760, 760f Eye, 1305–1328
968b, 968f Esophageal sphincter dysfunction, anatomy of, 1306f
Epidural hematoma, 1250–1251, 1251f lower, 757 anterior segment of, 1313–1315, 1315b
Epigenetic alterations, 184–185 Esophageal stenosis, 757 cataract, 1314
Epigenetic changes, in cancer, 319–320 Esophageal tumors, 762–764 endophthalmitis, 1314–1315
Epigenome, in cancer, 320 adenocarcinomas, 762–763, 763f, 763b functional anatomy, 1313, 1313f
Epineurium, 1218 squamous cell carcinoma, 763–764, 763f and glaucoma, 1314
Epispadias, 963 Esophageal varices, 517, 760– panophthalmitis, 1314–1315, 1315f
Epithelial basement membranes, invasion of, 761, 760b, 761f conjunctiva of, 1308–1309, 1309b
by tumor cells, 307f Esophagitis, 758–762 functional anatomy of, 1308–1309, 1308f
Epithelial cell injury, in glomerular chemical and infectious, 758, 758b–759b, 759f neoplasms, 1309, 1310f
disease, 905, 905f due to lacerations, 758, 758t pinguecula, 1309
Epithelial cells, 190 reflux, 759–760, 759f pterygium, 1309
Epithelial hyperplasia, of Esophagus, 757–764 scarring of, 1309
breast, 1043f, 1043b achalasia of, 757–758 cornea of, 1310–1312
Epithelial-to-mesenchymal transition agenesis of, 754 degenerations and dystrophies, 1311–1312, 1312b
(EMT), in metastasis, 307, 307f Barrett, 761–762, 761f–762f, 761b–762b functional anatomy of, 1310–1311, 1311f
Epithelial tumors, 1017–1023, 1023b Essential thrombocytosis (ET), 625– keratitis in, 1311, 1311f
benign, 1142–1143 626, 626f ulcers in, 1311
acanthosis nigricans, 1143 Esthesioneuroblastoma, 741 end-stage, 1328
epithelial cyst (wen), 1143 Estrogen deficiency, 1180 eyelid of, 1307–1308, 1308b
fibroepithelial polyp, 1143 Estrogen exposure, and breast cancer, 1046– functional anatomy of, 1307–1308, 1308f
seborrheic keratoses, 1142 1047 neoplasms of, 1308, 1308f, 1308b
Epithelioid cells, 100 Estrogen receptors (ER), in breast movement disorders, in paraneoplastic
Epithelioid carcinoma, 1045, 1060 syndrome, 1302
hemangioendothelioma, 522, 872 ET, Essential thrombocytosis optic nerve of, 1325–1327, 1327b
Epithelium, alveolar, 674 État criblé, 1255–1256 anterior ischemic optic neuropathy, 1325–
Epitope spreading, 221 Ethanol 1326, 1326f
Epstein-Barr virus (EBV), 357–358 CNS toxicity of, 1292 glaucomatous damage of, 1326, 1326b, 1327f
in Burkitt lymphoma, 325, 326f, 357–358 effects of, 418 neuritis of, 1327
clinical features of, 358 metabolism of, 419f neuropathies of, 1326–1327
in immune response, 196 ETS genes, in prostate cancer, 979 papilledema, 1326, 1326f
morphology of, 358b Euchromatin, 4f orbit of, 1306–1307, 1307b
oncogenic potential of, 325–326 Euploid, 165 functional anatomy of, 1306–1307
pathogenesis of, 357–358 Ewing sarcoma family tumors, 1192– inflammatory conditions of, 1306–1307
ER, Endoplasmic reticulum 1193, 1193f, 1193b, 1197b neoplasms of, 1307
ERBB1 gene, 287 Excessive scarring, 110–111 proptosis, 1306–1307
ERBB2 gene, 287, 317–318 Excoriation, 1135t thyroid ophthalmopathy, 1307f
Erosion, 1135t Executioner caspases, 46 retina, 1318–1325, 1325b
Erysipelas, 361f, 361b in apoptosis, 302–303 age-related macular degeneration, 1323–1324
Erythema, 117–118 Exocytosis, 11, 1135t artery and vein occlusions, 1323
infectiosum, perinatal infection with, 462, 462f Exogenous pyrogens, 101–102 degenerations of, 1324
multiforme, 1156, 1156f Exostosis, 1189–1190 functional anatomy, 1318–1319, 1318f
lymphoma, 1325 fallopian tubes, 1015 aggressive, 111
neoplasms in, 1324–1325 gestational and placental disorders of, 1028– of breast, 1063
retinal detachment, 1319–1320, 1319f 1035 Fibromuscular dysplasia, 487
retinitis, 1324 of early pregnancy, 1029–1030 of renal artery, 936f, 936b–937b
retrolental fibroplasia, 1322–1323 of late pregnancy, 1030–1033 Fibromuscular intimal hyperplasia, 493
vascular disease, 1320–1322 infections of, 986–989 Fibronectin, 24, 26f
sclera of, 1310 myometrium, tumors of, 1014–1015 Fibropolycystic disease, of liver, 860
uvea of, 1315–1318, 1318b ovaries, 1016–1028 Fibrosis
neoplasms in, 1316–1318 uterus, 1001–1016 of breast, 1042b
nevi and melanomas in, 1316–1318, 1317f, 1317b vagina, 994–995 due to ionizing radiation, 431f–432f, 432
uveitis, 1316 vulva, 989–993 in inflammation, 95, 95f
vitreous of, 1318–1325 Ferritin, 655–656 in parenchymal organs, 110, 111f
Fetal alcohol syndrome, 420, 456 in systemic sclerosis, 232
Fetal chromosomal anomalies, 1029 in tissue repair, 103
Fetal growth restriction, 457–461 Fibrothecomas, ovarian, 1027
F Fetal hemoglobin (HbF), 641 Fibrotic scar, in infarcts, 134f
Factitial panniculitis, 1166 Fetal hydrops, 462–464 Fibrous ankylosis, 1201b
Factor V Leiden, and thrombosis, 127 clinical features of, 464 Fibrous capsule, of tumor, 273
Factor VIII, 667–668, 667f immune, 462–463, 463f Fibrous cortical
Factor VIII deficiency, 668–669 morphology of, 463b–464b defect, 1195, 1195f, 1195b, 1197b
Factor VIII-vWF complex, 667–668, 667f nonimmune, 463–464, 464f Fibrous dysplasia, 1195–
Factor IX deficiency, 669 Fetal infection, 458 1196, 1196f, 1196b–1197b
FADD, Fas-associated death domain Fetal influences, on fetal growth Fibrous histiocytoma, benign, 1149, 1150f
Fallopian tubes, 1015 restriction, 458 Fibrous proliferative lesions, of oral
inflammations of, 1015 Fetal macrosomia, 456 cavity, 732–733, 732f
tumors and cysts of, 1016 Fever, in inflammation, 101–102 Fibrous tumors, of infants and children, 476
Familial amyloid polyneuropathies, 1225 Fever blisters, 354b–355b Fifth disease of childhood, perinatal
Familial breast cancer, 314–315, 1047 FFAs, Free fatty acids infection with, 462, 462f
Familial hematuria, benign, 922–923 FGF, Fibroblast growth factor FIH, Familial isolated hypoparathyroidism
Familial hypercholesterolemia, 151– FGF receptor 3 (FGFR3), 1175 Filariasis, edema due to, 116–117
154, 154b Fiber intake, and colon cancer, 449 Filtration slits, 898, 900f
Familial isolated hypoparathyroidism Fibrillary glomerulonephritis, 920 Fine-needle aspiration, of tumors, 331
(FIH), 1097 Fibrillin, 148–149 First-degree relatives, with breast
Familial Mediterranean fever, 262 in congenital heart disease, 536 cancer, 1047
Familial medullary thyroid cancer, 1130 Fibrillin-1, 148–149 FISH, Fluorescence in situ hybridization
Familial melanoma syndrome, 1148t Fibrin Fish, methyl mercury in, 413
Familial mental retardation 1 (FMR1), 143 in coagulation cascade, 120–121 Fish oil, for inflammation, 88
Familial mental retardation protein in hemostasis, 118–119 Fistulas
(FMRP), 176–177, 177f Fibrin split products, in fibrinolysis, 122– arteriovenous, 487
Familial paraganglioma 1, 1127t 123 congenital vesicouterine, 955
Familial paraganglioma 3, 1127t Fibrin thrombi, 138b tracheoesophageal, 754f
Familial paraganglioma 4, 1127t Fibrinogen, 102 Flare-ups, 229
Familial tumor syndromes, 1302–1303 in coagulation cascade, 122 Flax, asthma due to, 692t
Fanconi anemia, 314, 659 Fibrinoid necrosis, 40b–41b, 41f FLIP, and apoptosis, 45–46
Farmer's lung, 698 of arterioles, in malignant Flow cytometry, 332–333
Fas (CD95), in immunologic tolerance, 217– hypertension, 936b, 938f Fluid movement, in capillary walls, 116f
218 Fibrinolysis, 122–123 Fluorescence in situ hybridization
Fas-associated death domain (FADD), in Fibrinolytic cascade, 122–123, 123f (FISH), 182–183
apoptosis, 45–46 Fibrinolytic effects, of endothelium, 124 FMR1, Familial mental retardation 1
Fas ligand (FasL) Fibroadenoma, of FMRP, Familial mental retardation protein
in apoptosis, 45–46 breast, 273f, 1062, 1062f, 1062b Foam cells, in atherosclerosis, 497
in immunologic tolerance, 217–218 Fibroblast growth factor Focal adhesion complexes, 13
Fascioscapulohumeral dystrophy, 1234 (FGF), 20t, 21, 1173 Focal cerebral ischemia, 1253–1254
Fat embolism, 131–132 in benign prostatic hyperplasia, 976 Focal lupus nephritis, 225b–228b
Fat necrosis, 40b–41b, 41f, 885f, 885b Fibroblast growth factor receptor-3 Focal segmental glomerulosclerosis
of breast, 1041, 1041b (FGFR3), 1142 (FSGS), 906, 907t
Fat-soluble vitamins, 436, 443t Fibrocystic changes, 1042, 1042b Folate, deficiency of, 1223
Fatty change, 37, 62, 63f Fibroelastoma, papillary, cardiac, 579– Folate deficiency anemia, 651t, 654–655
Fatty liver, Hepatic steatosis 580, 579b Folic acid, dietary sources of, 654–655
Fatty liver disease, 842–848 Fibroepithelial polyps, 1143, 1143b Folic acid antagonists, 655
Fatty streaks, in atherosclerosis, 499b– of ureters, 954 Folic acid deficiency anemia, 651t, 654
502b, 500f of vulva, 990–991 Follicles, in peripheral lymphoid
Favism, 640 Fibroids, uterine, 1014 organs, 197
Feedback inhibition, 1065–1066 Fibrolamellar carcinoma, 869b–870b, 870f Follicular adenomas, of
Felons, 360b Fibroma(s), 268 thyroid, 1085, 1085f, 1092b
Felty syndrome, 606 of oral cavity Follicular carcinomas
Female genital tract, 985–1036 irritation, 732, 732f clinical course of, 1090
cervix, 995–1001 peripheral ossifying, 732 morphology of, 1089b
embryology and anatomy of, 986f ovarian, 1027, 1027f in thyroid, 1089–1090, 1090f, 1092b
endometrium, 1001–1016 Fibromatosis(es), 1211, 1211b, 1212f Follicular dendritic cell, 196
Follicular helper T cells (TFH), in humoral Funisitis, 458 diaphragmatic hernia, omphalocele, and
immunity, 203 Furuncle, 360b gastroschisis, 754
Follicular hyperplasia, 589f, 589b, 1084b Fusobacterium necrophorum, 379 ectopia, 755
Follicular inclusion cyst, 1143 Hirschsprung disease, 755–756, 756f, 756b
Follicular lipping, 1158b Meckel diverticulum, 755, 755f
Follicular lymphoma, 595t, 599–600, 599f– pyloric stenosis, 755
600f, 604b–605b G esophagus in, 757–764, 764b
morphology of, 599b G banding, 164–165, 164f achalasia of, 757–758
Follicular tonsillitis, 740 G-protein, 19, 1068 Barrett, 761–762, 761f–762f, 761b–762b
Foot processes, 898, 900f G protein-coupled receptors esophagitis of, 758–762, 758t, 758b–759b, 759f
Foramen ovale, patent, 537 (GPCRs), 19, 192 obstruction of, 757
Forebrain anomalies, 1246–1247 in inflammation, 79, 86 tumors of, 762–764, 763f, 763b–764b
Foregut cysts, 674 G1/S checkpoint varices of, 760–761, 760b, 761f
Foregut neuroendocrine tumors, 778 in cell cycle, 290 infections via, 340–341, 340t
Foreign bodies role of RB in regulating, 294f peritoneal cavity of, 820
inflammation due to, 74 G2/M checkpoint, in cell cycle, 290 infection of, 820
tissue repair and, 108 Galactocerebroside b-galactosidase, inflammatory disease of, 820, 820b
Foreign body granulomas, 100 deficiency of, 1290 sclerosing retroperitonitis of, 820
Formaldehyde, in indoor air pollution, 410 Galactosemia, 466 tumors of, 820
Formed elements, of blood, 584, 585f Gallbladder, 872–877 small intestine and colon in, 780–819
sequestration of, 629 congenital anomalies in, 872 acute appendicitis of, 818–819, 819b
Fornix, 1308–1309 diseases of, 877b–878b anal canal tumors of, 818, 818f
FOXP3, in immunologic tolerance, 217 Gallbladder adenocarcinoma, 877f angiodysplasia of, 783
Fractalkine, 90 Gallbladder carcinoma, 876–877, 877b appendix tumors of, 819
Fracture contusions, of skull, 1249 Gallbladder empyema, 875b graft-versus-host disease of, 805–806
Fractures, 1183–1185 Gallstones, 873–875 hemorrhoids of, 818, 819b
healing of, 1184–1185, 1184f morphology of, 874b infectious enterocolitis of, 787–798, 788t
Fragile X-associated tremor/ataxia obesity and, 448 inflammatory bowel disease of, 798–804, 799f
syndrome, 177 in pancreatitis, 882 irritable bowel syndrome of, 798
Fragile-X syndrome, 174–177, 175f– risk factors for, 873t ischemic bowel disease of, 781–783, 781b–
176f, 177b, 182f Gametocytes, of malaria, 389 782b, 782f
Frameshift mutation, 142–143 Gangliogliomas, 1298 malabsorption and diarrhea of, 783–787, 783t
Frank-Starling mechanism, 530 Ganglion cysts, 1207 obstruction of, 780–781
Freckle, 1135, 1135b–1136b Ganglioneuromas, 478f polyps of, 807–811, 817b–818b
Free fatty acids (FFAs), in insulin Gangrene, 133 stomach in, 764–779
resistance, 1104 of lower extremities, due to diabetes dysplasia of, 771
Free radicals mellitus, 1108b–1109b gastritis of, 765–766, 765f, 766b, 773b
cell injury due to, 52–53, 52t, 53f Gangrenous necrosis, 40b–41b hypertrophic gastropathies of, 771–773, 772t
generation of, 52–53, 53f Gap junctions, 13 Ménétrier disease of, 771–772, 772f, 772b
pathologic effects of, 53 GAPs, GTPase-activating proteins mucosal atrophy and intestinal metaplasia of, 771
removal of, 53, 53f Gardnerella vaginalis, 988 peptic ulcer disease of, 770–771, 770f, 770b–771b
Friedreich ataxia, 1287 Gartner duct cysts, 986, 994 polyps of, 773–779
Frontal bossing, 440b–442b Gas gangrene, 380 tumors of, 773–779
Frontotemporal dementia (FTD), 1280 Gastric adenocarcinoma, 774–776, 775f– Zollinger-Ellison syndrome of, 773
Frontotemporal lobar degenerations 776f, 775b–776b Gastropathies, hypertrophic, 771–773, 772t
(FTLDs), 1280–1282, 1281f Gastric adenoma, 774, 774b Gastroschisis, 754
Fructose-6-phosphate, hexosamine pathways Gastric antral vascular ectasia (GAVE), 766 GATA4, in congenital heart disease, 535–
and generation of, 1108 Gastric lymphomas, Helicobacter 536, 535t
Frustrated phagocytosis, 84 pylori and, 327 Gaucher cells, 159f, 159b
FSGS, Focal segmental glomerulosclerosis Gastrinomas, in pancreatic neuroendocrine Gaucher disease, 158–159, 159f
FTD, Frontotemporal dementia tumors, 1114 GAVE, Gastric antral vascular ectasia
FTLDs, Frontotemporal lobar degenerations Gastritis GBM, Glomerular basement membrane
FTLD-tau, 1282b acute, 765–766, 765f GDP, Guanosine diphosphate
FTLD-TDP, 1280–1282, 1282b autoimmune, 768–769, 768t, 769f, 769b
Fuchs endothelial dystrophy, of chronic, 766–771
cornea, 1312, 1312f cystica, 771 Gemistocytic astrocytes, 1242
Fulminant disseminated eosinophilic, 769 Gender, atherosclerosis and, 495
histoplasmosis, 712b granulomatous, 769–770 Gene amplification, in cancer, 317–318
“Fulminant liver failure,”, 826 Helicobacter pylori, 767–768, 767b, 768f, 768t Gene defects, associated with congenital
Functio laesa, 73, 95–96 lymphocytic, 769 heart disease, 535t
Functional endometrial disorders, 1002– uncommon forms of, 769–770 Gene editing, 6, 6f
1004 Gastroenteritis, climate change and, 406 Gene expression profiling, for breast
Fundic gland polyps, 773, 773b–774b Gastrointestinal anthrax, 363 carcinoma, 1060
Fungal infections, 383–388 Gastrointestinal stromal tumor (GIST), 778– Gene rearrangements, in oncogenes, 286–
aspergillosis, 387, 387b 779, 779f, 779b 287
candidiasis, 383–385, 384f, 384b–385b Gastrointestinal tract, 753–822 General paresis, of the insane, 1264b
cryptococcosis, 385–386, 385b and chronic alcoholism, 420 Generalized osteitis fibrosa cystica, 1181b
deep, of oral cavity, 733 congenital abnormalities of, 754–756, 756b– Generative lymphoid organs, 196
zygomycosis (mucormycosis), 387–388, 388b 757b Genes(s), and human diseases, 141–144
Fungal meningoencephalitis, 1268 atresia, fistulae, and duplications, 754, 754f Genetic analysis
array-based comparative genomic hybridization dysgerminoma, 1024–1025, 1025f, 1025b synthesis, 644, 646f
in, 183 ovarian, 1023–1025, 1023f, 1025b–1026b Globoid cells, in Krabbe disease, 1290
detection of DNA sequence alterations, 181–182yolk sac, 1025 Glomerular basement membrane
for epigenetic alterations, 184–185 teratomas, 1023–1024 (GBM), 898, 901b
polymerase chain reaction, 181–182, 182f testicular, 969–973 thickening of, 900
polymorphic markers in, 184 choriocarcinoma, 972, 972f, 972b Glomerular capillary basement
prenatal, 181 classification of, 969t, 970 membrane, 1108b–1109b
RNA analysis in, 185 clinical features of, 973 Glomerular crescents formation, 900
southern blotting in, 180, 182f embryonal carcinoma, 971, 971f–972f, 971b Glomerular diseases, 897–924, 898t
Genetic disorders, 141–188 environmental factors of, 969–970 dense deposit disease, 918–920, 920f
chromosomal, 164–173 genetic factors of, 970 focal segmental glomerulosclerosis, 906
complex multigenic, 163–164 mixed, 973 isolated abnormalities of, 920–923
due to copy number variations, 183 nonseminomatous, 973 mechanisms of progression in, 905–906, 906b
due to single nucleotide polymorphism, 183 pathogenesis of, 969–970, 969f with nephrotic syndrome, 896
molecular diagnosis of, 184 seminoma, 970, 970f–971f, 970b rapidly progressive (crescentic), 896
array-based comparative genomic hybridization spermatocytic, 970–971, 971b Glomerular filtration barrier, 898
in, 183 teratoma, 972–973, 972b–973b, 973f Glomerular filtration rate, in blood pressure
for epigenetic alterations, 184–185 yolk sac, 971, 972b regulation, 491
for genomic alterations, 182–184 Germinal center, in peripheral lymphoid Glomerular hyalinosis, 900–901
polymorphic markers in, 184 organs, 197 Glomerular hypercellularity, 900, 908b–
RNA analysis in, 185 Germinomas, in pineal gland, 1130 909b
southern blotting, 180, 182f Germline mutations, and breast Glomerular injury
prevalence of, 455–456 cancer, 1047–1049 mechanisms of, 901t, 903–904
single-gene Gestational disorder(s) mediators of, 904–905, 904f
Mendelian, 144–163 choriocarcinoma, 1034–1035, 1035f, 1035b pathogenesis of, 901–906, 902f, 906b
autosomal dominant, 145t ectopic pregnancy, 1029–1030 Glomerular lesions, associated with
autosomal recessive, 145–146, 146t gestational trophoblastic disease, 1033–1035 systemic diseases, 923–924, 923b
biochemical and molecular basis of, 147–148, 147t hydatidiform mole, 1033–1034, 1034f, 1034b Glomerular sclerosis, 900–901
due to defects in enzymes, 154–162 of placental implantation, 1031 Glomerulonephritis
due to defects in proteins that regulate cell growth, 163 placental infections, 1031, 1031f acute proliferative, 906–909, 908f
due to defects in receptor proteins, 151–154 placental site trophoblastic tumor, 1035 anti-GBM antibody induced, 901
due to defects in structural proteins, 148–151 preeclampsia and eclampsia, 1031–1033, 1032f– cell-mediated immunity in, 904
due to enzyme defects, 147–148, 147f 1033f circulating immune complexes, 903
Ehlers-Danlos syndromes, 149–151, 150t, 151b spontaneous abortion, 1029 fibrillary, 920
familial hypercholesterolemia, 151–154, 154b twin placentas, 1030–1031, 1030f Heymann model of, 912
Gaucher disease, 158–159 Gestational trophoblastic disease, 1033– membranoproliferative, 907t, 917–918
glycogen storage diseases, 160–162, 162b 1035 postinfectious, 906–907, 907t
lysosomal storage diseases, 154–160, 155f, 156t, 160b hydatidiform mole, 1033–1034, 1034f, 1034b poststreptococcal, 906–907
Marfan syndrome, 148–149, 151b GFAP, Glial fibrillary acidic protein primary, 907t
mucopolysaccharidoses, 160, 160b GH, Growth hormone rapidly progressive
Niemann-Pick disease type C, 158 Ghon complex, 371f, 371b–373b (crescentic), 898t, 907t, 909–
Niemann-Pick disease types A and B, 157–158, 158b Ghost cell glaucoma, 1314 911, 909t, 910f, 910b
Tay-Sachs disease, 156–157 Ghrelin, in energy balance, 444, 445f–446f Glomerulus, 898–900, 899f
transmission patterns of, 146b Giant cell arteritis, 511–512, 511f, 511b– immune complexes in, 903f
X-linked, 146, 146t 512b pathologic responses to injury, 900–901
with nonclassic inheritance, 173–180 Giant cell tumor, 1193–1194, 1193f, 1193b Glomus tumor, 520
Angelman syndrome as, 178–179 of tendon sheath, 1207 Glossitis, atrophic, due to vitamin
due to genomic imprinting, 178–179, 179b–180b Giardia lamblia, and parasitic B12 deficiency, 654b
due to gonadal mosaicism, 180 enterocolitis, 797 GLP-1 receptor agonists, 1100–1101
due to mutations in mitochondrial genes, 177–178 Gilbert syndrome, 853t Glucagon, 1097
fragile X syndrome and fragile X tremor/ataxia Gingivitis, 731–732 Glucocerebrosides, 158, 159b
as, 174, 177b Gingivostomatitis, 354b–355b Glucocorticoids, 1114–1115
Leber hereditary optic neuropathy, 177–178 GIP, Glucose-dependent insulinotropic tissue repair and, 108
Prader-Willi syndrome as, 178–179 polypeptide Glucocorticoid-remediable
Genetic heterogeneity, 144 GIST, Gastrointestinal stromal tumor aldosteronism, 1119
Genetic sex, 173 Glandular neoplastic lesions, 993 Glucokinase (GCK) genes, 1105
Genetics, atherosclerosis and, 494–495 Glanzmann thrombasthenia, 120, 666 Glucose-dependent insulinotropic
Genital herpes, 354b–355b Glaucoma, 1314 polypeptide (GIP), 1100–1101
Genital sex, 173 Glial cells, reactions to injury of, 1243 Glucose homeostasis, 1100–1101
Genital warts, of vulva, 991 Glial cells missing-2 (GCM2), 1097 Glucose-6-phosphate dehydrogenase
Genome, 1–6 Glial cytoplasmic inclusions, 1243 (G6PD) deficiency, 146, 640, 640f–
Genome-wide association studies (GWAS), Glial fibrillary acidic protein 641f, 650b
in type 2 diabetes mellitus, 1103 (GFAP), 1242, 1243f Glutathione (GSH), 1108
Genomic alterations, molecular analysis Glioblastoma, 1294b–1295b, 1295f Glutathione peroxidase, 83
of, 182–184 in oncogenes, 286 free radical removal by, 53
Genomic imprinting, 178–179, 179b–180b Gliomas, 1074, 1293–1298, 1294t Glycocalyx, 9
Genomic instability, in cancer, 314– Gliosis, 1242 Glycogen metabolism, 161f, 163f
315, 315b Global cerebral ischemia, 1256, 1256b– Glycogen storage diseases, 64, 160–
Germ cell tumors 1257b 162, 162b
choriocarcinoma, 1025 β-globin, 641 Glycogenoses, 64, 160–162, 162t
Glycolipids, 9 Granulomatous thyroiditis, 1080– HCV, Hepatitis C virus
Glycosaminoglycans, 23–24 1081, 1080f, 1080b HD, Huntington disease
Glycosylphosphatidylinositol (GPI), 648 Granulosa cell tumors, of ovaries, 1026– HDV, Hepatitis D virus
GM2 gangliosidosis, 156–157 1027, 1026f, 1026b Head and neck disorders, 731–752
GM-CSF, Granulocyte-macrophage colony- Granzymes, in T cell-mediated of ears, 744–745, 745b
stimulating factor cytotoxicity, 215 of neck, 745–746, 746b
GNAS gene, in pituitary tumors, 1069t Graves disease, 210t, 1081– of oral cavity, 731–739, 739b
GnRH, Gonadotropin-releasing hormone 1082, 1082f, 1082b aphthous ulcers, 732, 732f
Goiter in antibody-mediated hypersensitivity, 210 caries, 731
clinical course of, 1083 clinical course of, 1082 due to infections, 733
diffuse (nontoxic), 1083, 1083f morphology of, 1081b–1082b due to systemic disease, 733–734
intrathoracic/plunging, 1084b of orbit, 1306, 1307f fibrous proliferative lesions, 732–733, 732f
morphology of, 1083b pathogenesis of, 1081 gingivitis, 731–732
multinodular, 1083–1084, 1084f Gray (Gy), as radiation unit, 429 hairy leukoplakia, 733–734
Goitrous hypothyroidism, 1082–1083 Great arteries, transposition of, 539– inflammatory/reactive lesions, 732–733, 733b
Golgi apparatus, 6–7, 13 540, 539f–540f leukoplakia and erythroplakia, 734–735, 735f–736f
Gonadal mosaicism, 180 Greenhouse effect, 406 odontogenic cysts and tumors, 737–739, 737t–738t
Gonadal sex, 173 Ground-glass hepatocytes, on chronic periodontitis, 732
Gonadoblastoma, 1028 hepatitis, 837b–838b, 838f squamous cell carcinoma, 735–736, 736b–
testicular, 974 Ground-glass picture, due to neonatal 737b, 737f–738f
Gonadotroph(s), 1068t respiratory distress syndrome, 460 of salivary glands, 747–751, 748t, 751b
Gonadotroph adenomas, 1072 Growth factor(s) neoplasms, 738t, 748–751
Gonadotropin-releasing hormone in cell proliferation, 104 sialadenitis, 747–748
(GnRH), 435–436 in glomerular injury, 905 xerostomia, 747
Gonococcal infections, pelvic inflammatory involved in regeneration and repair, 20t of upper airways, 739–744, 744b
disease, 988–989 oncogenes for, 286 Healed pericarditis, 578–579
Gonococcal urethritis, 963 and receptors, 20–21 Healing, 103
Gonorrhea, epididymitis and orchitis due Growth factor receptors, oncogenes defects in, 110
to, 968 for, 286–287 by first intention, 108–109, 109f
Goodpasture syndrome, 210t, 704–705 Growth hormone (GH), in bone, 1173 by second intention, 109f, 110
glomerular disease in, 923 Growth hormone (GH)-secreting of skin wounds, 108–110
Gout, 1204–1205, 1205b, 1206f somatotroph adenomas, 1071 Health care-associated
classification of, 1204t Growth inhibition, insensitivity to, in pneumonia, 706t, 710–711
clinical course of, 1205 cancer, 284, 291–299 Heart, 527–582
pathogenesis of, 1204–1205, 1205f Growth plate, 1173, 1173f aging effects on, 529, 529t
Gouty nephropathy, 933, 1205b Growth signals, self-sufficiency in, in amyloidosis of, 263b–264b
GPCRs, Gprotein-coupled receptors cancer, 284–286 blood supply to, 528–529
GPI, Glycosylphosphatidylinositol Growth suppressors, removal of, in conduction system of, 528
GpIIb-IIIa deficiency, 120, 120f cancer, 315 morphology of, 532b–533b, 538b–539b
G-protein signaling, in pituitary GTPase-activating proteins (GAPs), 287 structure and specializations of, 528–529
adenomas, 1068, 1069f Guanosine diphosphate (GDP), 1068 tumors of, 579–580
Grading, of cancer, 330 Guillain-Barré syndrome, 1220 primary cardiac, 579–580, 579f
Graft survival, methods of increasing, 237– morphology of, 1221b Heart disease
238 Gummas, 376 carcinoid, 565
Graft-versus-host disease Gut hormones, in energy balance, 447 cardiomyopathies, 567–577
(GVHD), 239, 240f Gut microbiome, role of, 447 congenital, 534–541
Gram stain, 375, 1262 Guttata, 1311–1312 cyanotic, 538
Granulation, exuberant, 111 GVHD, Graft-versus-host disease with left-to-right shunts, 536–538, 538f
Granulation tissue, formation of, 105– GWAS, Genome-wide association studiesatrial septal defect, 536–537, 538f
106, 106f Gynecomastia, 1044, 1044f patent ductus arteriosus, 538, 538f
α-Granules, 119–120 patent foramen ovale, 537
Granulocyte-macrophage colony-stimulating ventricular septal defect, 537–538, 538f–539f
factor (GM-CSF), 699–700 obstructive, 540–541
Granuloma, 100 H aortic stenosis and atresia, 541
inguinale, 367, 367b H2O2, Hydrogen peroxide coarctation of the aorta, 540–541, 540f
of oral cavity H5N1 influenza virus, 710 pulmonary stenosis or atresia, 541
peripheral giant cell, 732–733 Hageman factor, in coagulation cascade, 122 with right-to-left shunts, 536, 538–540, 539f
pyogenic, 732, 733f Hairy cell leukemia, 595t, 603– persistent truncus arteriosus, 538
periapical, 738 604, 604f, 604b, 607b tetralogy of Fallot, 538–539, 539f
Granulomatosis, with polyangiitis, 514– Hairy leukoplakia, 733–734 total anomalous pulmonary venous connection, 538
515, 514b–515b Halo nevus, 1136t transposition of the great arteries, 539–540, 539f–540f
Granulomatous disease, 101 Halogenation, in phagocytosis, 82–83 tricuspid atresia, 538
Granulomatous inflammation, 100–101, 348 Hamartomas, 269–270 hypertensive, 555–556
diseases with, 101t Hand-Schüller-Christian triad, 628 pulmonary (right-sided), 556, 556f, 556t
morphology of, 100f, 100b–101b Haptoglobin, 637 systemic (left-sided), 555–556, 556f
in T cell-mediated hypersensitivity, 214, 214f Hashimoto thyroiditis, 1078– ischemic, 542–553
Granulomatous lobular mastitis, 1041 1080, 1079f, 1079b angina pectoris, 542–543
Granulomatous mastitis, 1041 Hashitoxicosis, 1080 chronic, 553, 553f, 553b–554b
Granulomatous orchitis, 968 HAV, Hepatitis A virus epidemiology of, 542
Granulomatous prostatitis, 975–976 HBV, Hepatitis B virus myocardial infarction, 543–553
clinical features of, 550–551, 551f radiation effects on, 431–432 platelets in, 119–120
consequences and complications of, 551–553, 552f Hematopoietic tissues primary, 118
pathogenesis of, 544–550 development/maintenance of, 584– secondary, 118–119
reperfusion of, 549–550, 550f 585, 584t, 585f, 585b–586b Hemostatic plug, 119f
reversible vs. irreversible, 545f, 547t, 549f morphology of, 585b–586b secondary, 120
right ventricular, 551 Hematuria Hemothorax, 725
subendocardial, 547 asymptomatic, 896 Hemp, asthma due to, 692t
transmural, 546–547 benign familial, 922–923 Henoch-Schönlein purpura, 923
triphenyltetrazolium chloride in, 547b–549b, 548f Hemidesmosome, 12–13 Hepadnaviridae, 832
pathogenesis of, 542 Hemochromatosis, 656–657, 848– Heparin, unfractionated, 127
sudden cardiac death due to, 542, 555 852, 849f, 852b Heparin-induced thrombocytopenia
myocarditis, 575–576 morphology of, 849b (HIT), 127, 665
pericardial, 577–579 Hemodialysis-associated amyloidosis, 262 Heparin-like molecules, 123–124
hemopericardium, 577 Hemodynamic disorders, 115–139 Hepatic adenoma, oral contraceptives
pericardial effusion, 577 edema, 115–117 in, 422
pericarditis, 577–579 hemorrhagic disorders, 118–130 Hepatic angiosarcoma, 522
tumors, 579–580 hyperemia and congestion, 117–118 Hepatic artery compromise, 861
primary cardiac, 579–580, 579f Hemoglobin Hepatic congestion, 118b
valvular, 557–567 adult reference range for, 637t Hepatic encephalopathy, 827, 1292
with calcification, 557–559, 558f mean cell, 635, 637t Hepatic necrosis, massive, 826b
endocarditis Hemoglobin C (HbC), 641 Hepatic steatosis (fatty liver), 843b–
infective, 563–564 Hemoglobin concentration, 635 844b, 844f
nonbacterial thrombotic endocarditis, 564 mean cell, 635, 637t Hepatic vein thrombosis, 862–863
noninfected vegetations, 564–565 in sickle cell disease, 641–642 Hepatic venous outflow obstruction, 862–
etiologies of acquired, 557, 558t Hemoglobin H (HbH) disease, 646t, 648 863
mitral valve prolapse, 559–560 Hemoglobin SC (HbSC) disease, 641 Hepatitis, viral, 836t
rheumatic, 560–563 Hemoglobinuria, paroxysmal Hepatitis A virus (HAV), 831–
Heart failure, 530–534, 534b cold, 650 832, 831f, 836t
left-sided, 532–533 nocturnal, 648–649 Hepatitis B virus (HBV), 832–833, 836t
right-sided, 533–534 Hemolysis infection, 832f–833f
therapy for, 534 extravascular, 637 oncogenic potential of, 326–327
Heart failure cells, 532b in β-thalassemia, 645 Hepatitis C virus (HCV), 834–835, 834f–
Heart fields, in cardiac development, 534 intravascular, 637 835f, 836t
Heart valves, 528 in paroxysmal nocturnal hemoglobinuria, 648 oncogenic potential of, 326–327
Heat cramps, 428 Hemolytic anemias, 637–650 related cirrhosis, 870f
Heat exhaustion, 428 classification of, 636t, 638 Hepatitis D virus (HDV), 835–836, 836t
Heat intolerance, in hyperthyroidism, 1076 due to glucose-6-phosphate dehydrogenase Hepatitis E virus (HEV), 836, 836t
Heat stroke, 428 deficiency, 640, 640f–641f Hepatoblastoma, 867–868, 867b, 868f
Heavy-chain disease, 607 due to hereditary spherocytosis, 638–640, 638f– Hepatocellular adenoma, 866–867, 867f
Heberden nodes, 1198–1199 639f β-catenin activated, 867
Hedgehog signaling pathway, 455–456 due to paroxysmal nocturnal morphology of, 867b
Heinz bodies, 640, 641f hemoglobinuria, 648 HNF1-α inactivated, 866
Helicobacter pylori, as carcinogen, 327 due to red cell trauma, 650, 650f morphology of, 867b
HELLP syndrome, 864 due to sickle cell disease, 641–644, 642f–643f inflammatory, 866–867
Helper T lymphocytes, in immune due to thalassemia syndromes, 644–648, 646t morphology of, 867b
system, 194–195, 202f immuno-, 649–650, 649t subtypes of, 868f
Hemangioblastomas, in von Hippel-Lindau microangiopathic, 650, 650f Hepatocellular carcinoma, 868–871, 869f
disease, 1303b morphology of, 638f, 638b aflatoxin and, 449
Hemangioendothelioma, 522 and systemic lupus erythematosus, 222t Hepatocellular liver disease, anemia due
Hemangioma(s), 519–520, 519f Hemolytic-uremic syndrome to, 661
capillary, 519–520 (HUS), 92, 665– Hepatocyte and parenchymal responses, in
cavernous, 520 666, 666t, 671b, 938, 939b liver disease, 824–825
in infants and children, 476, 476f Hemopericardium, 577 Hepatocyte apoptosis, 825, 825f
juvenile, 520 Hemophagocytic lymphohistiocytosis Hepatocyte growth factor (HGF), 20–21, 20t
pyogenic granulomas, 520 (HLH), 590 Hepatocyte necrosis, 825, 825f
Hemarthrosis, 125 Hemophilia A, 668–669, 671b massive, 827f
Hematocele, 974 Hemophilia B, 669 Hepatocyte proliferation, 104
Hematocrit, 635 Hemorrhagic cystitis, 955b–956b Hepatolithiasis, 856f
adult reference range for, 637t Hemorrhagic disorders, 118–130 Hepatorenal syndrome, 827
Hematogenous spread, 275–276 Hemorrhagic (hypovolemic) shock, 125 Hepcidin, 102, 848
Hematologic (transplacental) Hemorrhoids, 517, 818, 819b in iron metabolism, 656, 657f
infections, 461–462, 462f Hemosiderin, 655–656 in β-thalassemia, 646
Hematoma, 125 intracellular accumulation of, 65 HER2, 1060–1061
epidural, 1250–1251, 1251f Hemosiderosis, 65 in breast cancer, 1046, 1048f, 1051, 1051f–
subdural, 1251f–1252f in hemolytic anemia, 637 1052f, 1056b–1058b, 1060–1061
Hematopoiesis, spleen and, 629 Hemostasis, 118–130 Hereditary angioedema, 91
Hematopoietic stem cells (HSCs), 584 coagulation cascade in, 120–123, 121f Hereditary hemochromatosis, 848, 849f
transplantation of, 238–240 endothelium in, 123–124 Hereditary hemorrhagic telangiectasia, 519
Hematopoietic system general sequence of events in, 118–119, 119f Hereditary hyperbilirubinemia, 853–
components of, 583 normal, 118–124, 119f 854, 853t
Hereditary motor/sensory Histiocytoses, 590 HTLV-1, Human T-cell leukemia virus type
neuropathies, 1224 Histologic methods, for diagnosis of 1
Hereditary nephritis, 922, 922f, 923b cancer, 331–332 Human genome, non-protein-coding
Hereditary nonpolyposis colon cancer Histone(s) sequences found in, 2, 2f
syndrome (HNPCC), 314 acetylation, 3 Human herpesvirus 8 (HHV8), 257, 520–
Hereditary predisposition, to cancer, 333 in cancer, 319 521
Hereditary pulmonary alveolar methylation, 3 Human immunodeficiency virus (HIV), 247
proteinosis, 700 organization of, 3–4, 4f B-cell function in, 252–253
Hereditary sensory neuropathies, phosphorylation, 3 B-cell hyperplasia, 258
with/without autonomic Histone modifying factors, 3 CDC classification categories of, 255t
neuropathy, 1225 Histoplasma capsulatum, 712 chronic infection with, 254–255
Hereditary spherocytosis (HS), 638– HIT, Heparin-induced thrombocytopenia clinical course of, 254f
640, 638f–639f, 650b HIV, Human immunodeficiency virus effect of antiretroviral drug therapy on, 258–259
clinical features of, 639–640 HIV-associated dementia, 1267 encephalitis due to, 1267, 1267f, 1267b
morphology of, 639b HLA, Human leukocyte antigen genome of, 249f
pathogenesis of, 638–639, 638f HLH, Hemophagocytic lymphohistiocytosis infection of cells by, 249–250
Heredofamilial amyloidosis, 262 HNPCC, Hereditary nonpolyposis colon life cycle of, 249–251, 250f
Heredofamilial congenital lymphedema, 518 cancer syndrome mechanism of T-cell depletion in, 251–252
Hermaphroditism, 173 Hodgkin lymphoma, 592– model for pathogenesis of B-cell lymphomas
Hernia 593, 607b, 611t, 616b in, 257f
diaphragmatic, 754 clinical staging of, 615t morphology of, 259b
hiatal, 760 Reed-Sternberg cells in, 258 natural history of, 253–255
intestinal, 780 subtypes of, 613t of non-T cells, 252
Herpes bronchopneumonia, 354b–355b Hollenhorst plaques, 1323 opportunistic infections with, 255–256, 256t
Herpes epithelial keratitis, 354b–355b Holoprosencephaly, 455–456, 1247 pathogenesis of infection, 248–253, 253f, 259b
Herpes esophagitis, 354b–355b Holt-Oram syndrome, 1176t peripheral neuropathy in, 1222
Herpes hepatitis, 354b–355b Homan sign, 517 primary infection of, 253–254
Herpes labialis, 733 Homeobox (HOX) proteins, 457 properties of, 248
Herpes simplex encephalitis, 354b–355b Homeostasis, 34–35 pulmonary disease in, 714
Herpes simplex virus (HSV), 354 defective protein, 68 structure of, 248, 248f
genital tract with, 987, 987f, 987b Homeostatic chemokines, 90 thrombocytopenia associated with, 665
of oral cavity, 733 Homer-Wright rosettes, 1193b transmission of, 247–248
type 1, encephalitis due to, 1265, 1265f, 1265b Homing, of tumor cells, in invasion and viral replication of, 250–251
type 2, encephalitis due to, 1266 metastasis, 308–309 Human leukocyte antigen (HLA), 198, 198f
Herpes simplex virus infection, in Homocysteine, elevated levels of, and Human leukocyte antigen (HLA) alleles,
AIDS, 256 thrombosis, 127 association with disease, 218–219, 219t
Herpes stromal keratitis, 354b–355b Homocystinuria, 496 Human papillomavirus (HPV), 278
Herpes zoster, 355 Homogeneous staining regions, in and cervical carcinoma, 992f, 998–999
encephalitis due to, 1266 cancer, 317–318 and condyloma acuminatum of penis, 964
Herpesvirus infections, 353– Homologous recombination, 432 female genital tract with, 986
357, 354f, 354b–355b DNA repair by, 314 oncogenic potential of, 324–325, 324f
Herpetic gingivostomatitis, acute, 733 Hormone replacement therapy (HRT), 421– and penile carcinoma, 964–965, 965b–966b
Herpetic stomatitis, recurrent, 733 422 and vulvar intraepithelial neoplasia, 991, 992f
Heterochromatin, 4f Horseshoe kidneys, 941 Human T-cell leukemia virus type 1
Heteroplasmy, 177–178, 1291 Host cell metabolism, manipulation of, 343 (HTLV-1), 324
HEV, Hepatitis E virus Host damage, by microbes, 345–347, 347b Humoral immunity, 193, 201–203
Hexosaminidase a-subunit deficiency, 156– Host defenses, against tumors Hunner ulcers, 956
157 antitumor effector mechanisms in, 311, 311f Hunter, John, 73
Heymann model, of glomerulonephritis, 912 immune surveillance and escape as, 309– Hunter syndrome, 160
HGF, Hepatocyte growth factor 313, 313b Huntingtin, 145, 1285
HHD, Hypertensive heart disease mechanism of, 311–313, 313f Huntington disease (HD), 1285–
HHS, Hyperosmolar hyperosmotic tumor antigens in, 309–310 1286, 1286f, 1286b
syndrome Host immune response, evasion of, in Hurler syndrome, 160
HHV8, Human herpesvirus 8 cancer, 284 Hürthle cells, 1079f, 1079b, 1086f
Hiatal hernia, 760 Host immunity HUS, Hemolytic-uremic syndrome
Hibernation, of myocardium, 550 to infections, vitamin A in, 437 Hyalin, 900
Hidradenitis, 360b injurious effects of, 344 Hyaline arteriolosclerosis, 492b–493b
High-density lipoprotein (HDL) cholesterol, Host-microbial interactions, in inflammatory in benign nephrosclerosis, 935f
and atherosclerosis, 495–496 bowel disease, 800 due to diabetes mellitus, 1108b–1109b
High-fiber diet, protective effect of, and Host-pathogen interactions, 343–345 Hyaline cartilage, 1197
colon cancer, 449 Howell-Jolly bodies, in sickle cell Hyaline change, 64
High-grade squamous intraepithelial lesion disease, 642b Hyaline membrane disease, 459, 460f
(HSIL), 997 HPV, Human papillomavirus Hyaline membranes, 676
Hilus cell tumors, 1028 HRAS gene, in pituitary tumors, 1069t Hyaluronan, 23–24, 24f
Hindgut neuroendocrine tumors, 778 HRT, Hormone replacement therapy Hydatid cysts, 839
Hirschsprung disease, 755–756, 756f, 756b HS, Hereditary spherocytosis Hydatid disease, 395–396
Histamine HSCs, Hematopoietic stem cells Hydatidiform mole, 1033–
in asthma, 684 HSIL, High-grade squamous intraepithelial 1034, 1034f, 1034b
in immediate hypersensitivity, 207 lesion Hydatids of Morgagni, 1016
in inflammation, 86 HSV, Herpes simplex virus Hydrocarbons, 416
Hydrocele, 974 primary, 1093–1096, 1130 Hypopituitarism, 1067, 1072–1073
Hydrocephalus, 1244, 1244f secondary, 1096 genetic defects, 1073
ex vacuo, 1244 Hyperpituitarism, 1067–1072, 1072b radiation, 1073
posttraumatic, 1252 Hyperplasia, 59, 455 Hypoplasia, 455
Hydrogen peroxide (H2O2) compensatory, 59 pulmonary, 674
cell injury due to, 52t hormonal, 59 Hypoplastic left heart syndrome, 541
in phagocytosis, 82–83 mechanisms of, 59 Hypoproteinemia, edema due to, 116
Hydromyelia, 1248 pathologic, 59 Hypopyon, 1311
Hydronephrosis, 945–946, 946f, 954 physiologic, 59 Hypospadias, 963
Hydropic swelling, 1135t Hyperplastic arteriolosclerosis, 492b–493b Hypotension, 489
Hydrops, corneal, 1312b Hyperprolactinemia, 1071 Hypothalamic lesions, 1073
Hydrops fetalis, due to α-thalassemia, 648 Hypersensitivity, 204 Hypothalamic suprasellar
Hydrosalpinx, 989b Hypersensitivity diseases, classification tumors, 1074, 1074b
Hydrostatic pressure, increased, edema due of, 204–205 Hypothalamus-pituitary-thyroid axis, 1075f
to, 116 Hypersensitivity pneumonitis, 698 Hypothermia, 428
Hydroureter, 954 organic dusts that induce, 692t Hypothyroidism, 1077–1078
Hydroxychloroquine, 1230 Hypersensitivity reactions autoimmune, 1077
25-Hydroxycholecalciferol (25-OH- delayed-type, chronic inflammation due to, 96 causes of, 1077t
D), 439, 439f inflammation due to, 74 cretinism, 1078
5-Hydroxyeicosatetraenoic acid, in mechanisms of, 204t Hashimoto thyroiditis, 1081
inflammation, 88 Hypersplenism, 629 iatrogenic, 1077–1078
Hydroxyl radical Hypertension, 493b, 496 myxedema, 1078
cell injury due to, 52t aortic dissection, 507 Hypotonic infant, differential diagnosis
in inflammation, 82–83 chronic, 496 of, 1235–1236
5-Hydroxytryptamine, in inflammation, 86 environmental factors, 492 Hypotonicity, plasma membrane, 10
Hygiene hypothesis, 208 essential, 489, 492 Hypotrophy, 455
Hyperacute rejection, 236f, 236b genetic factors, 492 Hypoventilation syndrome, obesity in, 448
Hyperaldosteronism pathogenesis of, 492 Hypoxia, 36
clinical course of, 1119–1120 during pregnancy, 458 cerebral, 1253–1256
morphology of, 1119b in retinal vascular disease, 1320, 1320f–1321f inflammation due to, 73
primary, 492, 1118–1120, 1119f secondary, 492 Hypoxia-inducible factor-1, 56
secondary, 1119 types and causes of, 490t Hypoxic cell injury, 55–56
Hyperbilirubinemia vascular pathology in, 492, 493f Hypoxic encephalopathy, in left-sided heart
due to hemolytic anemia, 637 Hypertensive heart disease (HHD), 555– failure, 533
pathophysiology of, 853 556, 555b, 557b
Hypercalcemia pulmonary (right-sided), 556, 556f, 556t
causes of, 1095t systemic (left-sided), 555–556, 556f
in metastatic calcification, 66 Hypertensive vascular disease, 489–492 I
and nephrocalcinosis, 933 Hyperthermia, 428 IAP, Inhibitors of apoptosis protein
paraneoplastic syndromes and, 329 Hyperthyroidism, 210t, 1075–1077, 1076f Iatrogenic hypothyroidism, 1077–1078
Hypercholesterolemia, 498 clinical course of, 1076–1077 Ichthyosis, 1152–1153, 1153f, 1153b
and atherosclerosis, 495–496 Graves disease, 1081 ICU myopathy, 1230–1231
Hypercoagulability, in thrombosis, 126– Hypertonicity, plasma membrane, 10 IDH, Isocitrate dehydrogenase
128, 126t Hypertrophic cardiomyopathy, 572– IDH1 gene, 1191
Hypercortisolism, 1115–1118, 1118b 574, 573f, 573b IDH2 gene, 1191
Hyperdynamic circulation, 828–829 Hypertrophic osteoarthropathy, due to Idiopathic orbital
Hyperemia, 117–118 cancer, 330 inflammation, 1307, 1307f, 1307b
Hyperestrogenemia, 828 Hypertrophic scar, 110 Idiopathic/primary osteoarthritis, 1198
Hyperglycemia Hypertrophy, 35f, 57–59, 58f, 455 Idiopathic pulmonary arterial
neurologic sequelae of, 1292 mechanisms of, 57–59, 58f hypertension, 703, 703f
in septic shock, 137 Hyperuricemia, 1204 Idiopathic pulmonary fibrosis (IPF), 688–
Hypergranulosis, 1135t Hyperviscosity, and thrombosis, 126 690, 689b–690b
Hyperhomocysteinemia, 496 Hyperviscosity syndrome, 610–611 clinical features of, 690
Hyper-IgM syndrome, 244–245 Hypervitaminosis A, 438 pathogenesis of, 689, 689f
Hyperinsulinemia, obesity and cancer, 448 Hypervitaminosis D, in children, 442 environmental factors, 689
Hyperinsulinism, 1113–1114, 1113b Hypoadrenalism, 1124b genetic factors, 689
Hyperkeratinization, of the epidermis, due to secondary, 1125b Idiopathic pulmonary hemosiderosis, 704
vitamin A deficiency, 438 Hypocalcemia, 439–440 IDL, Intermediate-density lipoprotein
Hyperkeratosis, 1135t Hypocalcemic tetany, 438 α-1-iduronidase, 160
Hyperlipidemia, and atherosclerosis, 495– Hypochlorite, in phagocytosis, 82–83 IFIH1 gene, autoimmune diseases and, 219t
496 Hypochondroplasia, 1176t IgA nephropathy, 907t, 920–
Hypermutated/MSI (microsatellite Hypochromic microcytic anemia, 635 922, 921f, 921b, 923b
instability) tumors, 1008 of iron deficiency, 658f, 658b IgE-coated mast cells, 206
Hyperosmolar hyperosmotic syndrome Hypocitraturia, 947 IHD, Ischemic heart disease
(HHS), 1106 Hypoglycemia, 1106–1107 Ihh, Indian hedgehog
Hyperparathyroidism, 1093– neurologic sequelae of, 1292 IL2RA gene, autoimmune diseases and, 219t
1096, 1095f, 1096b, 1180– Hypogonadism, 828 IL23R gene, autoimmune diseases and, 219t
1181, 1181f, 1181b Hypokalemia, 1120 ILCs, Innate lymphoid cells
clinical features of, 1095–1096 Hypoparathyroidism, 1096–1097 Immature malignant
morphology of, 1094b–1095b Hypoperfusion, 138b teratomas, 1024, 1024f, 1024b
Immediate (type I) polyarteritis nodosa and other vasculitides, 234 Indirect Coombs antiglobulin test, 649
hypersensitivity, 204t, 205–208, 208b– systemic sclerosis (scleroderma), 231–234 Indoor air pollution, 410
209b hypersensitivity reactions, inflammation due Induced pluripotent stem cells (iPS
examples of disorders caused by, 208t to, 74 cells), 29–30, 30f
local, 208 Immune thrombocytopenia, 663–664 Inducible nitric oxide synthase (iNOS), 83
mediators of, 206–207 Immune thrombocytopenic purpura Industrial exposures, 414–418
phases of, 205f (ITP), 671b Industrial hazards, carcinoma and, 716
sequence of events in, 206f acute, 665 Infant mortality rate, 453
Immediate reaction, after allergen chronic, 664–665 Infants
exposure, 205 clinical features of, 664–665 causes of death in, 453, 456t
Immediate transient response, in morphology of, 664b congenital anomalies in, 453–457
inflammation, 76 pathogenesis of, 664 causes of, 455–457, 456t
Immune complex(es) Immunity pathogenesis of, 456–457, 457f
deposition of, 211 adaptive (acquired, specific), 190 diseases of, 453
formation of, 211 innate (natural, native), 190 fetal hydrops in, 462–464
pathogenesis of diseases caused by, 212b Immunodeficiency, 240 clinical features of, 464
and tissue injury, 212 associated with systemic diseases, 245–246 immune, 462–463, 463f
Immune complex-associated vasculitis, 509– common variable, 245 morphology of, 463b–464b
510 primary nonimmune, 463–464, 464f
Immune complex-mediated (type III) hyper-IgM syndrome, 244–245 inborn errors of metabolism in, 464–473
hypersensitivity, 204t, 210–212, 211f isolated IgA deficiency, 245 perinatal infections in, 461–462
examples of, 211t Wiskott-Aldrich syndrome, 246 premature, 457–461
local, 212 Immunodeficiency diseases, 204 necrotizing enterocolitis in, 460–461, 461f
morphology of, 212b Immunodeficiency-associated large B-cell neonatal respiratory distress syndrome in, 459–
Immune destruction, evasion of, in lymphoma, 601 460, 459f–460f
cancer, 316 Immunoglobulin A (IgA), in humoral risk factors for, 457–458
Immune dysregulation, Polyendocrinopathy, immunity, 203 sudden infant death syndrome in, 473–
Enteropathy, X-linked (IPEX), 217 Immunoglobulin E (IgE), 1154 475, 474t, 474b
Immune evasion, by microbes, 343– in asthma, 684 tumors and tumor-like lesions in, 475–483
344, 343f, 344b Immunoglobulin E (IgE) antibody, benign, 475–477, 476f
Immune granulomas, 100 production of, 205–206 malignant, 477, 477t
Immune-privileged sites, 217–218 Immunoglobulin G (IgG), in humoral Infarct(s)
Immune reactions, inflammation due to, 74 immunity, 203 defined, 133
Immune reconstitution inflammatory Immunoglobulin G4-related disease (IgG4- factors that influence development of, 134
syndrome, 258–259 RD), 234, 235f, 506b morphology of, 133b–134b
Immune responses Immunohemolytic anemia, 649– red, 133f, 133b–134b
adaptive immunity in, 193–198 650, 649f, 649t, 650b splenic, in sickle cell disease, 643f, 644
cell-mediated immunity in, 193, 200– Immunohistochemistry, 332 white, 133f, 133b–134b
201, 201f, 203b–204b Immunologic disorder, and systemic lupus Infarction(s), 133–134, 134b
cells of immune system in, 193–196 erythematosus, 222t myocardial, 543–553
cytokines in, 199–200 Immunologic memory, 203–204 clinical features of, 550–551, 551f
decline of, 203–204 Immunologic reactions, cell injury due consequences and complications of, 551–553, 552f
humoral immunity in, 201–203, 202f to, 36 pathogenesis of, 544–550
lymphocyte activation and, 200–204 Immunologic tolerance, 216–218 patterns of, 546–549, 546f
normal, 190–204, 203b–204b and autoimmunity, 221b reperfusion of, 549–550, 550f
Immune surveillance, 309–313, 313b Immunologically mediated tissue reversible vs. irreversible, 545f, 547t, 549f
Immune system injury, 204–215 right ventricular, 551
cells of, 193–196 Immunoregulatory pathways, activation of, subendocardial, 547
diseases of, 189–266 in immune evasion, 312 and thrombosis, 126
evasion of, 311–312, 312f Immunosuppression-associated Kaposi transmural, 546–547
immunodeficiency diseases, 240–259 sarcoma, 521–522 triphenyltetrazolium chloride in, 547b–549b, 548f
messenger molecules of, 199–200 Immunosuppressive factors, secretion of, by septic, 133b–134b
tissues of, 196–198 cancer cells, 312
Immune system disorder(s) Imperforate anus, 754
amyloidosis, 263f, 264b–265b Impetigo, 1168, 1168b–1169b Infection(s), 986–989
of aging, 263 Inactive plaques, in multiple acute (transient), 349–353
classification of, 260–264, 261t sclerosis, 1270b–1271b bacterial, 359–382, 359t
endocrine, 263 Inborn errors of metabolism, 464–473, 465t bleeding disorders due to, 663
hemodialysis-associated, 262 cystic fibrosis, 466–473, 469f–472f central nervous system, 1260b–
heredofamilial, 262 clinical features of, 472–473, 472t 1261b, 1261t, 1269b
localized, 262–263 environmental modifiers of, 470–473 abscess
pathogenesis of, 260–264, 261f genetic modifiers of, 470–473 brain, 1262–1263
plasma cell disorders associated with, 261–262 morphology of, 471b extradural, 1263
primary, 261–262 galactosemia, 466 acute focal suppurative, 1262–1263
properties of amyloid and, 259–260 phenylketonuria, 465–466, 466f acute meningitis, 1261–1262
reactive systemic, 262 Inclusion body myositis, 1230, 1230f meningoencephalitis
vascular, 264 morphology of, 1230b chronic bacterial, 1263–1264
autoimmune Incomplete penetrance, 144–145 fungal, 1268
chronic discoid lupus erythematosus, 229 Indian hedgehog (Ihh), 1173 viral, 1264–1268
mixed connective tissue disease, 234 Indirect-acting carcinogens, 322 protozoal, 1268–1269
subdural empyema, 1263 tissue injury mediated by, 84 chronic, 1157–1158
emphysema, 680 morphologic patterns of, 93–94 lichen planus, 1158
of female genital tract, 986–989 outcomes of, 95, 95f psoriasis, 1157
fetal, 458 reactions of blood vessels in, 75–76 seborrheic dermatitis, 1158
fungal, 383–388 stimuli for, 73–74 Inflammatory disorders, 1004
host defenses against, 343–344 summary of, 95–96 of breast, 1040–1041, 1042b
host immunity to, vitamin A in, 437 termination of, 85 duct ectasia, 1041, 1041f
inflammation due to vascular reactions in, 76b fat necrosis, 1041
acute, 73 in Alzheimer disease, 1277 lymphocytic mastopathy, 1041
chronic, 96 anemia of chronic disease due to, 658 mastitis
intrauterine, 458 antibody-mediated, 210 acute, 1040
involving the lower and upper genital in asthma, 684 granulomatous, 1041
tract, 988–989 of bladder, 955–957, 956f periductal, 1040
of lower genital tract, 987–988 causes of, 73–74 Inflammatory lesions, larynx, 743
and malnutrition, 434 chronic, 96–101, 349 Inflammatory myopathies, 234, 1228–1230
of oral cavity, 733 causes of, 96 Inflammatory neuropathies, 1220–1222
parasitic, 388–399 cells and mediators of, 97–100 Inflammatory reactions
in people with immunodeficiencies, 344–345 defined, 73 diseases caused by, 73t
perinatal, 461–462 macrophages in, 97–98 nature of leukocyte infiltrates in, 80f
skin disorders due to, 1166–1169 morphological features of, 96–97, 96f role of mediators in, 92t
impetigo, 1168 other cells in, 99–100 Inflammatory response
molluscum contagiosum, 1168 progression to, 95 components of, 72, 72f
superficial fungal, 1169 and scarring, 349, 349f in septic shock, 135–136
verrucae (warts), 1167 chronic bronchitis and, 681 Inhalational anthrax, 363
spectrum of inflammatory responses to, 347– consequences of, 72 Inherited genetic alterations, indications for
349, 348t cytokines in, 89f, 89t analysis of, 180–181
staphylococcal, 359–360, 359f, 361f defined, 71 Inherited peripheral neuropathies, 1224–
streptococcal and enterococcal, 360–361 fibrinous, 93–94, 93f 1225
tissue repair and, 108 general features of, 74b Inhibin, in granulosa cell tumors, 1026–
transient, 349–353 granulomatous, 100–101, 347–348, 348f 1027
urinary tract, 897, 927–931, 927f harmful consequences of, 72 Inhibitors of apoptosis protein (IAP), 302–
viral, 349–358, 349t historical highlights of, 73 303
Infectious agent(s) in innate immunity, 192 Initial innate immune response, 218
of cancer, 278 local and systemic, 72–73 Initiation, of chemical carcinogenesis, 321t
cell injury due to, 36 macrophages in, chronic, 97f–98f Injury, resolution of, 676
special techniques for diagnosing, 401– mediators of, 73, 85–92, 85t INK4α, in osteosarcoma, 1188
402, 402t actions of, 93b Inlet patch, 755
vertical transmission of, 341 cell-derived, 85–86 Innate immunity, 74, 190–193, 190f
Infectious disease(s), 339–403 arachidonic acid metabolites, 86–88 components of, 190–191
bacterial, 359–382, 359t cytokines and chemokines, 88–90 defects in, 241–242, 241t
emerging, 400–401, 401t neuropeptides, 92 reactions of, 192–193
fungal, 383–388 nitric oxide, 83 Innate lymphoid cells (ILCs), 190–191
microbial pathogenesis of, 339–349 platelet-activating factor, 92 iNOS, Inducible nitric oxide synthase
microorganisms cause disease, 340–342, 342b– reactive oxygen species, 82–83 Insecticides, as air pollutants, 692t
343b vasoactive amines (histamine and serotonin), 86 Insulin, 1097
parasitic, 388–399 plasma protein-derived elevated, levels of, 448–449
viral, 349–358, 349t complement system, 90–92 in energy balance, 444, 445f
Infectious neuropathies, 1222 kinins, 92 in glucose homeostasis, 1100f
Infectious rhinitis, 739 products of coagulation, 92 regulation of, release, 1100–1101
Infectious vasculitis, 516 mononuclear, 347–348, 348f resistance, obesity in, 448
cerebral infarction due to, 1254 overview of, 71–74 Insulin action, 1101
Infective endocarditis, 563–564, 563f, 563b– of penis, 963–964 genetic defects in, 1105
564b, 564t of prostate, 975–976 target cell, 1102f
Inferior vena cava syndrome, 517–518 purulent (suppurative), 94, 94f, 347, 360f Insulin-like growth factor 1 (IGF-1), in
Infiltrative ophthalmopathy, 1081 recognition of microbes and damaged cells cellular aging, 68
Inflammasome, 74, 191–192, 192f, 1204– in, 74 Insulin receptor, 1101
1205 and repair of damaged tissues, 103 Insulin resistance, 1104
in type 2 diabetes mellitus, 1105 serous, 93, 93f in septic shock, 137
Inflammation, 71–113, 496, 498, 499f systemic effects of, 101–102, 102b in type 2 diabetes mellitus, 1104
acute, 75–96 of testis and epididymis, 967–968, 968f Insulin-resistant diabetes, 210t
cardinal signs of, 73 ulcers due to, 94, 94f Insulin signaling pathways, 1101
components of, 75 of urethra, 963 Insulitis, 1108b–1109b
defined, 73 Inflammatory AAAs, 506b Integrins, 13, 24–25, 26f
due to infections, 73 Inflammatory bowel disease, 213t in inflammation, 78, 78t
leukocytes in Inflammatory carcinoma, of breast, 1060 Intercapillary glomerulosclerosis, 1108b–
clearance of offending agents, 80–85 Inflammatory dermatoses, 1159b 1109b
other functional responses of activated, 84–85 acute, 1153–1154 Interdigitating dendritic cells, 196
recruitment to sites of inflammation, 77–80, 77f, 79b– eczematous dermatitis, 1154–1155 Interferons, type I, in systemic lupus
80b erythema multiforme, 1156 erythematosus, 224
removal of offending agents, 85b urticaria, 1153–1154 Interferon regulatory factors (IRFs), 191
Interleukins, in immune responses, 199 due to volvulus, 781 Ion channels, 1176–1178
Interleukin-1 (IL-1), in inflammation, 88–90 polyps of, 807–811, 817b–818b Ion channel myopathies
Interleukin-6 (IL-6) in familial adenomatous polyposis, 812– (channelopathies), 1236
anemia of chronic disease due to, 658–659 813, 813f, 813t Ionizing radiation, in cancer, 323
in inflammation, 90 hamartomatous, 808–810, 808b, 809t IPEX, Immune dysregulation,
Interleukin-8 (IL-8), 90 hyperplastic, 807, 807f, 807b Polyendocrinopathy, Enteropathy, X-
Interleukin-17 (IL-17), in inflammation, 90 inflammatory, 808, 808f linked
Intermediate-density lipoprotein (IDL), juvenile, 808–809, 808b, 810f IPF, Idiopathic pulmonary fibrosis
cholesterol metabolism and neoplastic, 810–811, 811f–812f, 811b IPMNs, Intraductal papillary mucinous
transport, 151–152 in Peutz-Jeghers syndrome, 809–810, 809b– neoplasms
Intermediate filaments, 12 810b, 810f iPS cells, Induced pluripotent stem cells
Internal elastic lamina, of blood sigmoid diverticulitis of, 806, 806f, 806b IRF5 gene, autoimmune diseases and, 219t
vessels, 485–486 Intima, of blood vessels, 485–486 IRFs, Interferon regulatory factors
Internode, 1217–1218 Intimal thickening, in response to vascular Iris, 1306f
Interstitial cystitis, 956 injury, 488–489 Iris bombé, 1314
Interstitial matrix, 22 Intra-alveolar fluid, accumulation of, 676 Iron
Interstitium Intracellular accumulations, 62–65, 62f, 66b absorption, 656, 657f
pulmonary, 674 of glycogen, 64 distribution in body of, 655, 655t
surrounding, 674 hyaline change, 64 requirements for, 655
Intestinal obstruction, 780–781, 780f of lipids, 62–63, 63f Iron-binding capacity, 658
Intestinal volvulus, 781 of pigments, 64–65, 65f Iron deficiency anemia, 655–
Intestinalization, due to vitamin of proteins, 63–64, 63f 658, 655t, 657f, 661b–662b
B12 deficiency, 654b Intracellular bacteria, 346 clinical features of, 658
Intestine, 780–819, 787b, 798b, 806b–807b infections caused by other, 381–382 etiology of, 657–658
acute appendicitis of, 818–819, 819b virulence of, 347–348 morphology of, 658b
anal canal tumors of, 818, 818f Intracellular catabolism, 14f pathogenesis of, 658
angiodysplasia of, 783 Intracellular destruction, of microbes and Iron metabolism, 655–657, 655t, 656f–657f
appendix tumors of, 819 debris, 81–83, 82f Iron overload
colitis of Intracellular microbes, elimination of, 200– classification of, 848t
diversion, 805, 805f 201 in β-thalassemia major, 647
indeterminate, 803–804 Intracellular receptors, 17 Iron oxide, 692t
microscopic, 805, 805f Intracranial hemorrhage, 1257–1260 Irritable bowel syndrome, 798
colorectal cancer of due to vascular malformations, 1260 Irritation fibroma, of oral cavity, 732, 732f
adenocarcinoma, 813–817, 815f–817f, 816b, 817t– intraparenchymal, 1250, 1257, 1257b, 1258f Ischemia, inflammation due to, 74
818t subarachnoid (due to ruptured saccular Ischemia-reperfusion injury, 56
hereditary non-polyposis, 813, 813t aneurysms), 1258–1260 Ischemic bowel disease, 781–783, 781b–
graft-versus-host disease of, 805–806 Intracranial pressure, raised, 1244–1245 782b, 782f
hemorrhoids of, 818, 819b Intraductal papillary mucinous neoplasms Ischemic cardiomyopathy, 553
infectious enterocolitis of, 787–798, 788t (IPMNs), 889–890, 890f, 890b Ischemic cell injury, 55–56
Campylobacter, 789–790, 789b, 790f Intraductal papilloma, of breast, 1044f Ischemic heart disease (IHD), 542–553
due to cholera, 787–789, 789f Intrahepatic angina pectoris, 542–543
due to Escherichia coli, 792–793 cholangiocarcinoma, 871, 871b–872b epidemiology of, 542
due to salmonellosis, 791, 791b Intrahepatic cholestasis, of pregnancy, 865 myocardial infarction, 543–553
due to shigellosis, 790–791, 790b Intralobar sequestration, 674 clinical features of, 550–551, 551f
due to typhoid fever, 791–792 Intraluminal digestion, 783 consequences and complications of, 551–553, 552f
due to Whipple disease, 794, 794f, 794b Intramural arteries, 528 pathogenesis of, 544–550
due to Yersinia, 792, 792b Intranuclear basophilic inclusions, 356b reperfusion of, 549–550, 550f
parasitic, 795–798 Intraparenchymal reversible vs. irreversible, 545f, 547t, 549f
pseudomembranous, 793, 793f, 793b hemorrhage, 1250, 1257, 1257b, 1258f right ventricular, 551
viral, 794–795, 796f Intraparenchymal metastases, 1301b subendocardial, 547
inflammatory bowel disease of, 798–804, 799f Intrarenal reflux, 928 transmural, 546–547
colitis-associated neoplasia due to, 804, 805f Intraretinal microangiopathy, 1108b–1109b triphenyltetrazolium chloride in, 547b–549b, 548f
Crohn disease, 799t, 800–801, 800b–801b, 801f– Intrauterine infection, prematurity due pathogenesis of, 542
802f to, 458 sudden cardiac death due to, 542, 555
ulcerative colitis, 799t, 801–803, 802b–803b, 803f– Intravascular hemolysis, 637 Ischemic necrosis, in hypopituitarism, 1073
804f in paroxysmal nocturnal hemoglobinuria, 648 Islet cell tumors, 1113, 1114f
irritable bowel syndrome of, 798 Intrinsic factor in vitamin Islets of Langerhans, 1097
ischemic bowel disease of, 781–783, 781b– B12 metabolism, 652–653, 652f Isochromosome, 165–166, 166f
782b, 782f Invasion, in cancer, 306–309, 309b Isocitrate dehydrogenase (IDH), 301, 301f
malabsorption and diarrhea of, 783–787, 783t of extracellular matrix, 307–308 Isotype switching, in humoral
in abetalipoproteinemia, 787 vascular dissemination and homing of tumor immunity, 203
in autoimmune enteropathy, 786 cells in, 308–309 “Itai-Itai” disease, 413–414
in celiac disease, 784–786, 784f–785f, 785b Invasive (infiltrating) ITP, Immune thrombocytopenic purpura
in cystic fibrosis, 784 carcinoma, 1055, 1056b–
in environmental enteropathy, 786 1058b, 1059f, 1059t
in lactase (disaccharidase) deficiency, 786 Invasive ductal carcinoma, of breast, 274f
obstruction of, 780–781 Invasive thymoma, 632b–633b J
due to adhesions, 780–781 Inversion, 165, 166f JAG1, in congenital heart disease, 536
due to hernias, 780, 780f Involucrum, 1186b Jaundice, 853
due to intussusception, 781 Iodopsins, 436–437 causes of, 853t
due to fetal hydrops, 463 Klatskin tumors, 871b–872b LATs, Latency-associated viral RNA
due to hemolytic anemia, 637 Klebsiella, in pyogenic osteomyelitis, 1185– transcripts
obstructive, due to pancreatic carcinoma, 893 1186 LCIS, Lobular carcinoma in situ
in pregnancy, 864 Klinefelter syndrome, 170–171 Lead
JC virus, in AIDS, 256 Koilocytic atypia, in condyloma in environmental pollution, 411
Joints, 1171–1215 acuminatum, 991, 991f poisoning, 411, 411f–412f, 412b
crystal-induced arthritis of, 1204–1206 Koplik spots, 350b Leber hereditary optic neuropathy, 177–
infectious arthritis of, 1203–1204 Korsakoff syndrome, 1291 178, 178f
juvenile idiopathic arthritis, 1202 Krabbe disease, 1290, 1290f Lectin pathway, in complement system, 91
osteoarthritis of, 1198–1199, 1198f– Krukenberg tumor, 1028 Left bundle branches, 528
1199f, 1198b KS, Kaposi sarcoma Left shift, in inflammation, 102
rheumatoid arthritis of, 1199–1202, 1199f– Kuru plaques, 1275b Left-sided heart failure, 532–533
1202f, 1201b Kussmaul breathing, 1106 Left-sided hypertensive heart disease, 555–
seronegative spondyloarthropathies, 1202–1203 Kwashiorkor, 434–435, 434f 556, 556f
solid, 1197 Kyphoscoliosis, in Ehlers-Danlos Left-to-right shunts, 536–538, 538f
synovial, 1197 syndromes, 150 due to atrial septal defect, 536–537, 538f
in systemic lupus erythematosus, 225b–228b due to patent ductus arteriosus, 538, 538f
tumors and tumor-like conditions of, 1207–1208 due to patent foramen ovale, 537
Joubert syndrome, 1248 due to ventricular septal defect, 537–538, 538f–
Junctional epidermolysis bullosa, 1164f L 539f
Juvenile hemangiomas, 520 Labile tissues, 103 Left ventricular hypertrophy, 531f
Juvenile idiopathic arthritis, 1202 Lacerations, of brain, 1249 Legionnaires' disease, 707
Juvenile laryngeal papillomatosis, 743 Lactation, breast during, 1037–1038 Leigh syndrome, 1291
Juxtacortical chondromas, 1190 Lactational adenomas, 1042b Leiomyoma(s), 1014, 1014f, 1014b, 1213
Lactic acidosis, due to shock, 137–138 benign metastasizing, 1014b
Lactiferous ducts, squamous metaplasia of bladder, 962
of, 1040–1041, 1040f uterine, 1014
K Lactoferrin, in phagocytosis, 83 Leiomyosarcomas, 276f, 1213, 1213b
Kallikreins, in inflammation, 92 Lactotroph adenoma, 1068t, 1070–1071 uterine, 1014–1015, 1015f, 1015b
Kaposi sarcoma (KS), 520–521, 522f clinical course of, 1071 Leishmania donovani, 392f
in AIDS, 256 morphology of, 1070b Leishmania species, 391, 392b
orbital, 1308 Lactotroph hyperplasia, 1071 Leishmaniasis, 391–392
Kaposi sarcoma herpesvirus, 257, 520–521 Lacunar infarcts, 1255–1256, 1256f Lens, 1306f
Kartagener syndrome, 687 Lacunes, in hypertensive cerebrovascular Lentiginous, 1135t
Karyotyping, 164 disease, 1255–1256 Lentigo, 1136, 1136b
Kasabach-Merritt syndrome, 670b Lafora bodies, 1242 Lepromatous leprosy, 375f
Kawasaki disease, 513, 513b Lambert-Eaton myasthenic Lepromin, 374
Kayser-Fleischer rings, 850b syndrome, 722, 1226 Leprosy, 374, 374b–375b
KCNJ2, mutations of, 1236 in paraneoplastic syndrome, 1302 lepromatous (multibacillary), 374b–375b, 375f
Kearns-Sayre syndrome, 1235 Lambl excrescences, 579–580 peripheral neuropathy in, 1222
Keloid, 110, 112f Lamellar bone, 1185 tuberculoid (paucibacillary), 374b–375b, 375f
Keratic precipitates, 1314 Laminin, 24, 26f Leptin, in energy balance, 444, 445f–446f
Keratinizing squamous cell carcinomas, 991 Langerhans cell(s), 196, 1133–1134 Lesch-Nyhan syndrome, 1204
Keratinizing squamous metaplasia, 1040b– Langerhans cell histiocytosis, 590, 627– Leser-Trélat sign, 1142
1041b 628, 628f Lesions simulating primary
Keratinocyte growth factor (KGF), 20t multifocal multisystem, 627–628 neoplasms, 1195–1196
Keratinocytes, 1133, 1160f pulmonary, 628 Lethal factor (LF), in anthrax, 363
Keratoconjunctivitis sicca, in Sjögren unifocal/multifocal unisystem, 628 Letterer-Siwe disease, 627–628
syndrome, 229 Langhans giant cells, 100f, 100b–101b Leukemia, 269, 592
Keratoconus, corneal degenerations, 1311– Large bile duct obstruction, 854 Leukemoid reactions, in inflammation, 102
1312, 1312f, 1312b Large cell change, in liver, 869f, 869b–870b Leukocyte(s), in inflammation
Keratomalacia, 437–438, 438f morphology of, 869b–870b chemotaxis of, 79–80, 79f–80f
Kernicterus, due to fetal hydrops, 463, 465f Large granular lymphocytic clearance of offending agents by, 80–85
Keshan disease, 444t leukemia, 595t, 606–607, 607b margination, rolling, and adhesion to
Ketone bodies, 1106 Laryngeal carcinoma, 743–744, 744f, 744b endothelium of, 77
Ketonemia, 1106 Laryngeal chemoreceptors, in sudden infant migration through endothelium of, 78–79
Ketonuria, 1106 death syndrome, 475 other functional responses of activated, 84–85
KGF, Keratinocyte growth factor Laryngotracheobronchitis, 710b recognition of microbes and damaged cells, 74
Kidney(s), 895–952 Larynx, disorders of, 743–744 recruitment to sites of inflammation, 77–80, 77f
amyloidosis of, 263f, 263b–264b Laser-assisted in situ keratomileusis removal of offending agents by, 85b
in left-sided heart failure, 533 (LASIK), 1310 tissue injury mediated by, 84
myeloma, 934 LASIK, Laser-assisted in situ keratomileusis Leukocyte activation, in
neoplasms, 952b Late phase reaction, after allergen inflammation, 80, 81f, 85b
in systemic sclerosis, 232b exposure, 207–208 Leukocyte adhesion
Kidney grafts, rejection of, 235–237, 236b– Latency-associated viral RNA transcripts defects in, 241
237b, 239f (LATs), 354 in inflammation, 77–78
Kidney injury, acute, 896 Latent membrane protein-1 (LMP-1) molecules, 78t
Kimmelstiel-Wilson disease, 1108b–1109b gene, 325 Leukocyte function, defects in, 241
Kininogens, in inflammation, 92 Late-onset adrenal virilism, 1121 Leukocytoclastic vasculi, 1201b
Kinins, in inflammation, 92 Leukocytosis, 587–588
in inflammation, 102 and the bile ducts, 823–872 metaplastic lesions of, 957
mechanisms/causes of, 587t–588t cholestatic diseases in, 852–859, 859b neoplasms of, 957–962, 957t
Leukodystrophies, 1289–1290 and chronic alcoholism, 420 mesenchymal tumors, 962
Leukoerythroblastosis, 585b–586b circulatory disorders of, 861–863, 861f, 863b–secondary, 962
Leukopenia, 586–587 864b urothelial tumors, 957–962, 958f–959f, 959b–
in inflammation, 102 impaired blood flow into the, 861–862 960b, 961t
in systemic lupus erythematosus, 222t impaired blood flow through the, 862 obstruction of, 962
Leukoplakia infectious disorders of, 831–839 morphology of, 962b
hairy, 733–734 in infectious mononucleosis, 358b L-selectin, in inflammation, 78, 78t
of oral cavity, 734–735, 735b, 736f malignant neoplasms in, 867–872 LSIL, Low-grade squamous intraepithelial
of vulva, 990 metastasis in, 872 lesion
Leukotrienes, 684 with metastatic cancer, 275f Lung(s), 673–729
in immediate hypersensitivity, 207 nodules and tumors in, 865–872 farmer's, 698
in inflammation, 86, 88 nutmeg, 118f, 118b hamartoma, 724, 724f
pharmacologic inhibitors of, 88 in right-sided heart failure, 533b humidifier or air-conditioner, 698
Leukotriene B4 (LTB4), in inflammation, 79 Liver abscesses, 839 in left-sided heart failure, 532b
Lewis, Thomas, 73 Liver disease metastasis to, 275f
Lewy bodies, dementia with, 1283–1284 associated with pregnancy, 864–865 pigeon breeder's, 698
Lewy neurites, 1284 general features of, 824–831 shock, 138b
Leydig cell tumors, testicular, 974, 974b mechanisms of injury and repair, 824–826 in systemic lupus erythematosus, 225b–228b
Libman-Sacks disease, 565 laboratory evaluation of, 824t in systemic sclerosis, 232b
Libman-Sacks endocarditis, 128b– morphology of, 826b transplantation of, 714–715, 715f, 715b
129b, 228f regression in, 825–826 complications of, 714–715
Lichen planus, 1158, 1158b, 1159f scar formation in, 825–826, 827f Lung cancer
Lichen sclerosus, of vulva, 990, 990f Liver failure, 826–831, 831b genetic alterations in, 334f
Lichen simplex chronicus, of vulva, 990 acute, 826–827 and smoking, 416, 416t, 417f
Lichenification, 1135t chronic, 828 Lung disease(s)
Liddle syndrome, 492 Liver flukes, 839 carcinoma, 715–722, 717t, 717b–722b, 719f
Li-Fraumeni syndrome, 294–295 Liver infarct, 861f adenocarcinoma, 716–717
and breast cancer, 1047, 1049t Liver regeneration, 104–105, 104f adenocarcinoma in situ, 717b–721b, 718f
Ligamentum arteriosum, in coarctation of Liver tumors, 872b atypical adenomatous hyperplasia, 717b–721b, 718f
aorta, 540–541 LKB1 gene, 299 carcinoid, 723, 723f, 723b
Light-chain cast Lobular carcinoma, invasive, 1056 classification of, 717b–721b
nephropathy, 934, 934f, 934t, 934b Lobular carcinoma in situ clinical features of, 721–722, 722t
Light-chain deposition disease, 934 (LCIS), 1055, 1055b, 1056f combined carcinoma, 717b–721b
Limb-girdle muscular dystrophy, 1234 Lobular hyperplasia, atypical, 1045, 1045f etiology and pathogenesis of, 715–717
Limbic encephalitis, in paraneoplastic Lobule, pulmonary, 673–674 hamartoma, 724, 724f
syndrome, 1301 Local invasion, by neoplasm, 273, 276t inflammatory myofibroblastic, 724
Limit dextrin, 161 Local mass effect, in pituitary gland, 1067 large cell carcinoma, 717b–721b
Lines of Zahn, 128b–129b Localized amyloidosis, 262–263 lymphangioleiomyomatosis, 724
Linkage, 184 Localized cutaneous neurofibroma, 1237b– in mediastinum, 724, 724t
Lipids, intracellular accumulation of, 62–63 1238b metastatic, 724, 724b, 725f
Lipid-free radical, 53 Loeys-Dietz syndrome, aneurysms and, 505 miscellaneous, 723–724
Lipid/glycogen metabolism, diseases Long noncoding RNAs, 5–6 mucinous adenocarcinomas, 717b–721b
of, 1234 roles of, 5f secondary pathology of, 717b–721b
Lipid mediators, in immediate Long QT syndrome, and sudden cardiac small cell carcinoma, 717
hypersensitivity, 207 death, 554–555 squamous cell carcinoma, 716–717, 720f
Lipid rafts, 9 Longitudinal bone growth, 1173 staging of, 721, 721t
Lipofuscin Low blood pressure, 491 vascular, 700–705
intracellular accumulation of, 64–65, 65f Low-grade squamous intraepithelial lesion caused by air pollutants, 692t
neuronal inclusions of, 1242b (LSIL), 997, 997b, 998f, 1001b drug-induced, 696
Lipomas, 1209, 1209b Low-density lipoprotein (LDL) cholesterol, due to infections, 705–714
of breast, 1063 and atherosclerosis, 495–496 abscess of, 711–712, 711b–712b, 712f
cardiac, 579 Low-density lipoprotein (LDL) human immunodeficiency virus, 714
of spermatic cord, 969 metabolism, 151f eosinophilia of, 698
Lipoprotein α, 496 Low-density lipoprotein (LDL) receptor, in fibrosing, 688–696
Liposarcoma, 1209, 1209b, 1210f cholesterol metabolism, 152f–153f complications of therapies, 696–698
Lipoxins, in inflammation, 88 Lower urinary tract, 953–983 connective tissue diseases, pulmonary involvement
Lipoxygenase(s), in inflammation, 88 anatomy of, 953 in, 690–691
Lipoxygenase inhibitors, 88 ureters in, 954 cryptogenic organizing pneumonia, 690, 691f
Liquefactive necrosis, 40b–41b, 41f congenital anomalies of, 954, 954t nonspecific interstitial pneumonia, 690, 690b
Lisch nodules, 1302 inflammation of, 955b granulomatous, 696–698
Lissencephaly, 1247 obstructive lesions of, 954, 954t hypersensitivity pneumonitis, 698, 698f, 698b
Listeria monocytogenes, 362 tumors and tumor-like lesions of, 954, 954f sarcoidosis, 696–697, 696b–697b, 697f
Listeriosis, 362, 362b urethra in, 963 neuroendocrine proliferations of, 722–723
Liver, 823–879 inflammation of, 963 obstructive, 678–688, 678t, 679f
amyloidosis of, 263b–264b tumors and tumor-like lesions of, 963 of pleura, 725–727
anatomy of, 824f urinary bladder in, 955–962 effusion of, 725
bacterial, parasitic, and helminthic infections congenital anomalies of, 955, 955f malignant mesothelioma, 726–727, 727f, 727b
of, 839 inflammation of, 955–957, 956f pneumothorax, 725–726
solitary fibrous tumors of, 726, 726f, 726b Lymphogranuloma venereum, 381b Magnesium ammonium phosphate
tumors of, 726–727 Lymphoid cells, 315, 584 stones, 947, 947t
pulmonary alveolar proteinosis, 699–700, 700f– Lymphoid leukemias Major basic protein
701f, 700b common forms of, 604b–605b in chronic inflammation, 99–100
pulmonary Langerhans cell histiocytosis, 699 major types of, 595t in phagocytosis, 83
radiation-induced, 696 Lymphoid neoplasms, 590, 592–616, 592t Major histocompatibility complex (MHC)
restrictive, 688–700 immune cell antigens detected by monoclonal molecules, 198–199
smoking-related, 698–699 antibodies, 593t in immune system, 195
desquamative interstitial, 699, 699f, 699b origin of, 594f loss or reduced expression of, in immune
respiratory bronchiolitis-associated uncommon, 607b evasion, 312
interstitial, 699, 699b Lymphoid organogenesis, 99 Major histocompatibility complex (MHC)
surfactant dysfunction disorders, 700, 700b Lymphoid organs, tertiary, 99 restriction, 195
tumors of, 715–724 Lymphoid systems, radiation effects Malabsorption, 783–787, 783t
in vascular on, 431–432 in abetalipoproteinemia, 787
diffuse pulmonary hemorrhage syndromes, 703– Lymphoid tissues, 583 in autoimmune enteropathy, 786
705, 704f, 705b Lymphoma(s), 592 in celiac disease, 784–786, 784f–785f, 785b
pulmonary embolism, 700–702, 701f–702f, 701b– of breast, 1063 in cystic fibrosis, 784
702b common forms of, 604b–605b in environmental enteropathy, 786
pulmonary hypertension, 702–703, 703f–704f, 703b gastric, 776–777, 777f, 777b in lactase (disaccharidase) deficiency, 786
Lupus anticoagulant syndrome, 127 testicular, 974 Malakoplakia, cystitis with, 956, 956f, 956b
Lupus erythematosus, 691, 1166 Lymphopenia, 586 Malar rash, in systemic lupus
Lupus nephritis, 227f, 923 in systemic lupus erythematosus, 222t erythematosus, 222t
advanced sclerosing, 225b–228b Lymphoplasmacytic lymphoma, 610– Malaria, 388–390, 390b
Luteal cysts, 1016b 611, 610f, 611b Male breast, 1061
Lyme arthritis, 1203–1204 morphology of, 610b Male genital tract, 963–983
Lyme disease, 378–379, 379b, 1264 Lymphopoiesis, 585f penis in, 963–966
clinical stages of, 379f Lyon hypothesis, 170 congenital anomalies of, 963
peripheral neuropathy in, 1222 Lysosomal enzymes, 154–155 inflammation of, 963–964
Lymph node(s), 197 in inflammation, 83 tumors of, 964–966, 964f–965f
in acute inflammation, 76 in leukocyte-mediated tissue injury, 84 prostate in, 975–983
in infectious mononucleosis, 358b synthesis and intracellular transport of, 154f benign enlargement of, 976–977, 976f–977f, 976b–
morphology of, 197f Lysosomal enzyme arylsulfatase A, 1290 977b
reactive proliferations of, 587–590 Lysosomal membranes, injury to, 51 inflammation of, 975–976
Lymph node metastases, of breast carcinoma Lysosomal storage diseases, 154– normal anatomy and histology of, 975, 975f
Lymphadenitis, 76, 371b–373b, 588–590 160, 155f, 156t, 160b tumors of, 977–983, 979f–980f, 982t
morphology of, 589b Lysosomes, 7, 14–15 testis and epididymis in, 966–974
Lymphangioleiomyomatosis, 724 degradation of, 14f congenital anomalies of, 966–967, 967f
Lymphangitis, 76, 518 Lysozyme, in phagocytosis, 83 inflammation of, 967–968, 968f
Lymphatic filariasis, 398, 398b–399b regressive changes of, 967
Lymphatic obstruction, edema due to, 116– tumors of, 969–974, 969t, 974b
117 germ cell, 969–973
Lymphatic spread, 275 M gonadoblastoma, 974
Lymphatic transport, and M component, in myeloma, 607 lymphoma, 974
malabsorption, 783 MAC, Membrane attack complex of sex cord-gonadal stroma, 974
Lymphatic vessels, in acute Machado-Joseph disease, 1286–1287 spermatic cord and paratesticular, 969
inflammation, 76 Macrocytic anemia, 635 tunica vaginalis, 974
Lymphatics, 487 α2-macroglobulin, in inflammation, 83
vascular disorders of, 968, 968f
veins and, 517–518 Macronodular hyperplasia, 1116b–1117b Malformations, 454, 454f
Lymphedema, 116–117, 518 Macrophage(s), 190, 196 and developmental disorders, of central nervous
Lymphoblastic leukemias, acute, oncogenes activated, 97–98, 98f, 100, 106 system, 1245–1248
for, 288 alveolar, 674 of forebrain, 1246–1247
Lymphoblasts, 594 in glomerular injury, 904 neural tube defects, 1245–1246
Lymphocyte(s) in inflammation of posterior fossa, 1247
activation and function, defects in, 245 acute, 81t, 85 syringomyelia and hydromyelia, 1248
in chronic inflammation, 98–99, 99f chronic, 97–98, 97f–99f Malignancy, neuropathies associated
diversity, 193–194 in phagocytosis, 81–82 with, 1223–1224
principal classes of, 194f in repair, 106 Malignant biliary tumors, 871–872
recirculation, 197–198 in tuberculosis, 368–369 Malignant fibrous histiocytoma
of skin, 1134 Macrophage activation syndrome, 590 (MFH), 1214
Lymphocyte depletion type, of Hodgkin Macrophage inflammatory protein-1α (MIP- Malignant hypertension, 490
lymphoma, 612b–614b 1α), 90 Malignant hyperthermia, 428
Lymphocyte maturation, defects in, 244 Macrophage-lymphocyte interactions, in Malignant mixed Müllerian tumors
Lymphocyte predominance type, of chronic inflammation, 99f (MMMTs), 1012, 1012b, 1013f
Hodgkin lymphoma, 612b–614b, 614f Macrosomia, fetal, 456 Mallory hyaline, 843b–844b, 845f
Lymphocyte-rich type, of Hodgkin Macular degeneration, age-related, 92 Mallory-Weiss tears, 758
lymphoma, 612b–614b Macular edema, 1321b Malnutrition
Lymphocytic mastopathy, 1041 in diabetes, 1108b–1109b atrophy due to, 60
Lymphocytosis, in inflammation, 102 Macule, 1135t chronic alcoholism and, 420
Lymphoepithelioma-like carcinoma, 632b– Maffucci syndrome, 1190 climate change and, 406
633b
ignorance and failure of diet supplementation Media, of blood vessels, 486 due to defects in enzymes, 154–162
and, 433 Mediterranean lymphoma, 607 due to defects in proteins that regulate cell
primary, 433 Medullary carcinoma growth, 163
secondary, 433 of breast, 1056, 1059f due to defects in receptor proteins, 151–154
Mammalian target of rapamycin clinical course of, 1092 due to defects in structural proteins, 148–151
(mTOR), 287–288, 579–580 morphology of, 1091b–1092b due to enzyme defects, 147–148, 147f
Mammographic screening, 1039– of thyroid, 1091–1092, 1091f–1092f, 1092b Ehlers-Danlos syndromes, 149–151, 150t, 151b
1040, 1039f Medullary cystic disease, adult- familial hypercholesterolemia, 151–154, 154b
Mammosomatotroph, 1068t onset, 941t, 944f Gaucher disease, 158–159, 159f
Mannose-binding lectin, 74 Medullary sponge kidney, 941f, 941t, 944 glycogen storage diseases, 160–162, 162b
Mannose receptors Medulloblastoma, 1298–1299, 1298b– lysosomal storage diseases, 154–
in inflammation, 80 1299b, 1299f 160, 155f, 156t, 160b
in innate immunity, 192 Megakaryocytes, 585b–586b Marfan syndrome, 148–149, 151b
Mantle cell lymphoma, 595t, 602– Megalencephaly, 1246–1247 mucopolysaccharidoses, 160, 160b
603, 602b–603b, 603f, 607b Megalin, 912 Niemann-Pick disease
Marasmus, 434, 434f Megaloblastic anemia(s), 651–654, 661b– type C, 158
Marfan syndrome, 148–149, 151b 662b types A and B, 157–158, 158b
aneurysm and, 505 folate deficiency, 651t, 654–655 Tay-Sachs disease, 156–157
Marginal zone lymphoma, 603, 607b morphology of, 651f–652f, 651b–652b transmission patterns of, 144–146, 146b
extranodal, 595t pernicious (vitamin B12 deficiency), 651t, 652– X-linked, 146, 146t
Margination, 77–78 653 Ménétrier disease, 771–772, 772f, 772b
Marijuana, abuse of, 425–426 Megalocornea, 1326b Meningiomas, 1300–1301, 1300b–1301b
Marrow embolism, 131–132, 132f Melanin, intracellular accumulation of, 65 Meningitis
Mast cell(s) Melanocortin receptor 4 (MC4R), in energy acute, 1261–1262, 1262b
in inflammation, 100 balance, 446–447 aseptic (viral), 1262
sensitization and activation of, in immediate Melanocyte(s), 1133 pyogenic (bacterial), 1262, 1262f
hypersensitivity, 206 Melanocyte disorders, 1135–1142 cryptococcal, 1268, 1269f, 1269b
Mast cell mediators, in immediate dysplastic nevi, 1137–1138 defined, 1261
hypersensitivity, 207f freckle (ephelis), 1135 Meningocele, 1246
Mastalgia, 1038–1039 lentigo, 1136 Meningoencephalitis
Mastitis melanocytic (pigmented) nevus (mole), 1136– chronic bacterial, 1263–1264
acute, 1040 1137 defined, 1261
granulomatous, 1041 melanoma, 1139–1142 Meningomyelocele, 1246
periductal, 1040 α-Melanocyte-stimulating hormone (MSH), Meningovascular neurosyphilis, 1264b
Mastocytoma, 1152b in energy balance, 445–446 Menopausal hormone therapy (MHT), 421–
Mastocytosis, 1152, 1153f Melanocytic nevus, 1136– 422
Mastodynia, 1038–1039 1137, 1136b, 1137f, 1142b Menstrual cycle
Mastopathy, lymphocytic, 1041 representative variant forms of, 1136t breast changes during, 1037
Maternal abnormalities, in fetal growth Melanoma(s), 1139–1142, 1140f– endometrial histology in, 1001–1002, 1002f
restriction, 458 1141f, 1140b–1142b Mercury, in environmental pollution, 412–
Maternal endocrine factors, 1029 conjunctival, 1309 413
Maternal inheritance, 177–178 Melanoma antigen gene (MAGE) Merkel cell, 1134
Maternal vasculature, systemic disorders family, 310 Merlin, 1237
affecting, 1029 Melanomalytic glaucoma, 1314 Merozoites, of malaria, 389
Matrix metalloproteases (MMPs), 1172– MELAS, Mitochondrial MERRF, Myoclonic epilepsy and ragged red
1173 encephalomyopathy, lactic acidosis, and fibers
Matrix metalloproteinases (MMPs), 107– stroke-like episodes Mesangial cells, 898, 899f
108 Melittin, 206 Mesangial proliferative lupus
Maturity onset diabetes of the young Membrane attack complex (MAC), 91, 91f nephritis, 225b–228b
(MODY), 1105 Membrane permeability, defects in, cell Mesenchymal chondrosarcoma, 1192b
Mazabraud syndrome, 1195 injury due to, 51 Mesenchymal stem cells, 28
MB form of creatine kinase (CK-MB), in Membrane transport, 9–11 Mesenchymal tumors
myocardial infarction, 550 Membranoproliferative glomerulonephritis of bladder, 962
McCune-Albright syndrome, 1195 (MPGN), 907t, 917–918 of prostate, 983
cardiac myxomas in, 579 clinical features of, 918 Mesial temporal herniation, 1245
MCHC, Mean cell hemoglobin morphology of, 918f–919f, 918b Mesonephric ducts, 986, 986f
concentration pathogenesis of, 918 Metabolic abnormalities, in septic
MDM2, in osteosarcoma, 1188 secondary, 918 shock, 137
MDMA, 3,4 Membranous lupus nephritis, 225b–228b Metabolic acidosis, due to shock, 138
Methylenedioxymethamphetamine Membranous nephropathy, 907t, 933
MDS, Myelodysplastic syndromes Memory cells, 203
Mean cell hemoglobin, 635, 637t MEN1 gene, in pituitary tumors, 1069t Metabolic diseases
Mean cell hemoglobin concentration MEN1 mutations of central nervous system
(MCHC), 635, 637t in pancreatic neuroendocrine tumors, 1113 acquired, 1291–1293
in sickle cell disease, 637t, 641–642 in parathyroidism, 1094 Alexander disease, 1290
Mean cell volume, 635 Mendelian disorder(s), 144–163 due to hyperglycemia, 1292
adult reference range for, 637t autosomal dominant, 144–145, 145t due to hypoglycemia, 1292
Measles, 350, 350f, 350b autosomal recessive, 145–146, 146t due to vitamin deficiencies, 1291–1292
Mechanical factors, in tissue repair, 108 biochemical and molecular basis of, 147– genetic, 1289–1291
Mechanical trauma, 426–427 148, 147t hepatic encephalopathy, 1292
Krabbe disease, 1290, 1290f spread and dissemination of, 341– Mitochondrial membrane damage, 51
Leigh syndrome, 1291 342, 342f, 342b–343b Mitochondrial myopathies, 1235
leukodystrophies, 1290 vertical transmission, 341 morphology of, 1235b
mitochondrial encephalomyopathies, 1290–1291 Microbial carcinogenesis, 323–327 Mitochondrial pathway, of apoptosis, 45f
myoclonic epilepsy and ragged red fibers, 1291 Helicobacter pylori, 327 Mitoses, in neoplasia, 272
neuronal storage diseases, 1289 oncogenic DNA viruses, 324–327 Mitotic crisis, evasion of, 303–304, 304f
Pelizaeus-Merzbacher disease, 1290 oncogenic RNA viruses, 324 Mitral annular calcification, 559
neurologic sequelae of, 1292 Microbicidal activity, inherited defects Mitral valve prolapse (MVP), 559–
Metabolic ketoacidosis, 1106 in, 241 560, 559b
Metabolic syndrome, 447–448, 448f, 496 Microbiome, 340 in Marfan syndrome, 149b
Metabolism, cell growth and, in cancer, 301f Microcytic hypochromic anemia, 635 Mixed-cellularity type, of Hodgkin
Metachromasia, 1290 of iron deficiency, 658f, 658b lymphoma, 612b–614b, 614f
Metachromatic leukodystrophy, 1290 Microencephaly, 1246–1247 Mixed connective tissue disease, 234
Metals, in environmental pollution, 411– Microglia, reactions to injury of, 1243 Mixed tumors, 269–270, 269f
414, 414b Microglial nodules, 1243 testicular, 973
Metaphyseal dysplasia, 1176t in arthropod-borne viral encephalitis, 1264b– MMMTs, Malignant mixed Müllerian
Metaphyseal fibrous defects, 1195 1265b, 1265f tumors
Metaplasia, 272–273 in HIV encephalitis, 1267b MNA, Mini nutritional assessment
columnar to squamous, 61, 61f β2-microglobulin, in amyloidosis, 260 Mobile genetic elements, 2
connective tissue, 61 Micronodular hyperplasia, 1116b– MODY, Maturity onset diabetes of the
mechanisms of, 61 1117b, 1117f young
squamous to columnar, 61 Microorganism, 340–342 Mold infections, 386–388
Metaplastic carcinoma, of breast, 1056b– Micropapillary carcinoma, 1056b–1058b Moldy hay, hypersensitivity pneumonitis
1058b MicroRNAs (miRNAs), 4–5 due to, 692t
Metaplastic lesions, of bladder, 957 in cancer, 320 Molecular analysis, of genomic
Metaplastic theory, of endometriosis, 1005 generation of, 5f alterations, 182–184
Metastasis(es), 273–276, 306–309, 309b Microsatellite instability, 314 Molecular and cytogenetic diagnostics
of breast cancer, 274f, 1056b–1058b, 1058– Microscopic polyangiitis, 513–514, 514b for detection of minimal residual disease, 333
1059 glomerular lesions in, 923 of hereditary predisposition to cancer, 333
determination of site of origin of, 332 Microsomal ethanol-oxidizing system, 419f of malignant neoplasms, 333
invasion of extracellular matrix in, 307–308 Microtubules, 12 for prognosis of malignant neoplasms, 333
of prostate cancer, 979b–980b, 980f Microvascular disease, in systemic Molecular chaperone therapy, for lysosomal
vascular dissemination and homing of tumor sclerosis, 232 storage diseases, 155
cells in, 308–309 Microvascular occlusions, in sickle cell Molecular genetic diagnosis, 180–187
Metastatic calcification, 66 disease, 642, 642f array-based comparative genomic hybridization
Metastatic cascade, 306–307, 306f Microvascular thrombosis, 138b in, 183
Metastatic neoplasms, in Waterhouse- Microvillus inclusion disease, 786 diagnostic methods for, 180–181
Friderichsen syndrome, 1123–1124 Midgut neuroendocrine tumors, 778 for epigenetic alterations, 184–185
Metastatic tumors, 1196 Migratory thrombophlebitis, 130, 517 for genomic alterations, 182–184
of ovaries, 1028 due to cancer, 330 indications for testing in, 180–181
Metazoal infections, 394–399 Mikulicz syndrome, 231 polymorphic markers in, 184
Metchnikoff, Elie, 73 Milk-alkali syndrome, 66 RNA analysis in, 185
Methamphetamine, 425 Milk line remnants, 1038 southern blotting, 180, 182f
Methane, in greenhouse effect, 406 Milroy disease, 518 Molecular mimicry, in autoimmunity, 220
Methemoglobin, 637 Minamata disease, 413 Molecular profiles, of tumors, 334–335
Methicillin-resistant Staphylococcus Mineral dusts, inhalation of, 415 Molluscum contagiosum, 987–
aureus (MRSA), 360 Mineralocorticoids, 1114–1115 988, 988f, 1168, 1168f, 1168b
Methotrexate, for rheumatoid arthritis, 1202 Mini nutritional assessment (MNA), 435 Mönckeberg medial sclerosis, 493
α-methylacyl-coenzyme A-racemase Minimal mesangial lupus nephritis, 225b– Monoclonal gammopathies, neuropathies
(AMACR), in prostate cancer, 979b– 228b associated with, 1224
980b Minimal residual disease, detection of, 333 Monoclonal gammopathy of undetermined
Methylcobalamin, 653, 653f Misfolded proteins, accumulation of, significance (MGUS), 607, 610, 611b
3,4 Methylenedioxymethamphetamine apoptosis due to, 42 Monocyte(s)
(MDMA), 426 Missense mutations, 142 differentiation of, 585f
Methylmalonic acid, in vitamin Mitochondria, 8 in glomerular injury, 904–905
B12 deficiency, 653 energy generation of, 15–16 in inflammation
MFH, Malignant fibrous histiocytoma function of, 15–16 acute, 80
MGUS, Monoclonal gammopathy of roles of, 16f chronic, 97, 97f
undetermined significance Mitochondrial damage, cell injury due in innate immunity, 190
MHT, Menopausal hormone therapy to, 49–51, 50f Monocyte chemoattractant protein (MCP-
MI, Myocardial infarction Mitochondrial DNA (mtDNA), 177– 1), 90
Microaneurysms, 1108b–1109b, 1321b 178, 178f Monodermal teratomas, 1024
Microangiopathic hemolytic Mitochondrial dysfunction, in Parkinson Mononeuritis multiplex, 1220
anemia, 650, 650f disease, 1282–1283 Mononeuropathies, 1220
Microangiopathy, thrombotic, 665–666 Mitochondrial encephalomyopathies, 1289– Mononuclear phagocyte system, in chronic
Microbe(s) 1291 inflammation, 97
body transmission of, 342 Mitochondrial encephalomyopathy, lactic Mononucleosis, cytomegalovirus, 356–357
immune evasion by, 343–344, 343f, 344b acidosis, and stroke-like episodes Monosodium urate (MSU) crystals, 1204–
routes of entry of, 340–341, 340t (MELAS), 1291 1205
Mitochondrial genes, mutations in, 177–178 Monosomy, 165
Morton neuroma, 1224 Mural thrombus, due to myocardial right ventricular, 551
Mosaicism, 165 infarction, 552 subendocardial, 547
Motor unit, 1217 Muscle, 1217–1240 transmural, 546–547
Mott cells, 393b in sarcoidosis, 696b–697b triphenyltetrazolium chloride in, 547b–
MPGN, Membranoproliferative Muscleblind-like-1, 1234 549b, 548f
glomerulonephritis Muscular arteries, 486 Myocardial irritability, due to myocardial
MPO, Myeloperoxidase Muscular dystrophies, 1232–1234 infarction, 551–552
MPSs, Mucopolysaccharidoses Musculoskeletal system, in systemic Myocardial ischemia
MRSA, Methicillin-resistant Staphylococcus sclerosis, 232b causes of, 542
aureus Mutated genes, products of, as tumor consequences of, 543, 548f–549f
MS, Multiple sclerosis antigens, 310 coronary artery occlusion due to, 544
MSA, Multiple system atrophy Mutation(s), 142–144 reversible vs. irreversible, 545f, 547t, 549f
MSH, α-Melanocyte-stimulating hormone in cancer, 319t temporal progression of, 545, 545f, 545t
mTOR, Mammalian target of rapamycin within coding sequences, 142 Myocardial natriuretic peptides, 492
MUC5B gene, 689 due to deletions and insertions, 142–143, 143f Myocardial necrosis, progression of, 546f
Mucinous carcinoma, of breast, 1056b– frameshift, 142–143, 143f Myocardial response, to coronary artery
1058b, 1059f gain-of-function, 145 obstruction, 544–546, 544f–545f, 545t
Mucinous cystic neoplasms, of missense, 142 Myocardial rupture, due to myocardial
pancreas, 889, 889f within noncoding sequences, 142 infarction, 551, 552f
Mucinous tumors, of ovaries, 1020– nonsense, 142, 142f Myocardial vessel vasospasm, 517
1021, 1020b, 1021f point, 142, 143f Myocarditis, 575–576, 575t, 576f, 576b
Mucocele, of salivary glands, 747, 747f trinucleotide-repeat, 143, 173–177, 174t, 175f lethal acute, 393b–394b
Mucocutaneous leishmaniasis, 392b Mutational signature calling, 186 Myocardium, 528
Mucoepidermoid carcinoma, 750– MVP, Mitral valve prolapse hibernation, 550
751, 750f, 750b MX1 gene, expression of, 709–710 stunned, 550
Mucopolysaccharidoses Myasthenia gravis, 210t, 1225–1226 Myoclonic epilepsy and ragged red fibers
(MPSs), 160, 160b, 1178 in antibody-mediated hypersensitivity, 210 (MERRF), 1291
Mucormycosis, 387–388, 388f, 388b due to cancer, 330 Myofibroblastoma, of breast, 1063
Mucosal immunity, in inflammatory bowel MYC oncogene, 289–290, 300 Myofibroblasts, 107, 110
disease, 799–800 Mycobacterial arthritis, 1203 Myometrium
Mucus hypersecretion, 681 Mycobacterial infections, 367–374 leiomyoma of, 276f
Muir-Torre syndrome, 1148t Mycobacterial osteomyelitis, 1186 tumors of
Müllerian ducts, 986, 986f Mycobacterium leiomyomas, 1014, 1014f, 1014b
Müllerian-inhibiting substance, in avium complex, 373, 374f, 374b leiomyosarcomas, 1014–1015, 1015f, 1015b
cryptorchidism, 966 Mycobacterium leprae, 373 Myophagocytosis, 1228
Müllerian tumors, in ovaries, 1016 Mycoplasma hominis, 988 Myophosphorylase deficiency, 1234
Müller's muscle, 1076 Mycoplasmas, sexually transmitted Myosin deficient myopathy, 1230–1231
Multicystic encephalopathy, 1248 infections, 400t Myositis, autoimmune, autoantibodies
Multicystic renal dysplasia, 944, 945f Mycosis fungoides, 595t, 606 in, 222t
Multidrug resistance (MDR) protein, 9–10 Mycotic AAAs, 506b Myotonic dystrophy, 1234
Multifactorial inheritance, congenital Myelin figures, in cell injury, 40b Myxedema, 1078
anomalies due to, 456 Myelodysplasia, 621f pretibial, 1081
Multilobular meningioma, 1300f Myelodysplastic syndromes Myxoid liposarcoma, 1209b, 1210f
Multinodular goiter, 1083– (MDS), 590, 620–621, 627b Myxomas, cardiac, 579, 579f, 579b
1084, 1084f, 1084b morphology of, 620b–621b Myxomatous degeneration, of mitral
Multinucleated giant cells, in HIV Myelogenous leukemia, chronic, oncogenes valve, 559–560, 560f
encephalitis, 1267b for, 288, 288f Myxopapillary ependymomas, 1296b–1298b
Multiple endocrine neoplasia Myeloid neoplasms, 590, 616–628, 627b
type 1 (MEN-1), in Myeloid tissues, 583
parathyroidism, 1094, 1129–1130 Myeloma kidney, 608b–609b, 934
type 2 (MEN-2), 1130 Myelomeningocele, 1246, 1246f N
in parathyroidism, 1094 Myeloperoxidase (MPO), in NAD, Nicotinamide adenine dinucleotide
in pheochromocytoma, 1127t phagocytosis, 82–83 NADPH, Nicotinamide dinucleotide
type 2B (MEN-2B), 1127t Myelophthisic anemia, 661 phosphate
Multiple endocrine neoplasia Myeloproliferative disorders, 621–627, 627b NAFLD, Nonalcoholic fatty liver disease
syndromes, 1129–1130 tyrosine kinase mutations in, 622t Nail changes, due to psoriasis, 1157b–1158b
Multiple hereditary exostosis MYH9-USP6 fusion gene, 1211 Nail-patella syndrome, 1176t
syndrome, 1189–1190 Myocardial disease 2-Naphthylamine, and bladder cancer, 958
Multiple myeloma, 595t, 607–610, 608f– due to amyloidosis, 574, 575f Nasal polyps, 739, 740f
609f, 608b–609b, 611b due to cardiotoxic drugs, 577 Nasal ulcers, in systemic lupus
morphology of, 610b Myocardial hypertrophy, 35f, 58f erythematosus, 222t
Multiple sclerosis (MS), 213t, 1269– Myocardial infarction (MI), 543–553, 547b– Nasopharyngeal angiofibroma, 740–
1272, 1270b–1271b, 1271f–1272f 549b 741, 741f
HLA alleles and, 219t acute, and thrombosis, 126 Nasopharyngeal carcinoma, 741–743, 742f
Multiple system atrophy (MSA), 1284– clinical features of, 550–551, 551f Epstein-Barr virus in, 326
1285, 1285f, 1285b consequences and complications of, 551– Nasopharynx
Multipotent progenitors, 584 553, 552f disorders of, 740
Mumps, 350–351, 351b pathogenesis of, 544–550 inflammations of, 740
epididymitis and orchitis due to, 968 reperfusion of, 549–550, 550f tumors of, 740–743
reversible vs. irreversible, 545f, 547t, 549f Native immunity, 190
Natural immunity, 190 due to bile cast nephropathy, 935 spinocerebellar, 1286–1287
Natural killer cells, in immune due to hypercalcemia and nephrocalcinosis, 933 vascular (multi-infarct) dementia, 1273
response, 190–192, 192f, 203b–204b due to light-chain cast Neurofibrillary tangles, 1278b
NBCCS, Nevoid basal cell carcinoma nephropathy, 934, 934f, 934t, 934b Neurofibromas, 1237
syndrome due to urate nephropathy, 933, 933f morphology of, 1237b–1238b
Necator duodenale, and parasitic Nephrocalcinosis, 933 Neurofibromatosis, 1302
enterocolitis, 796 Nephrogenic adenoma, 957 Neurofibromatosis type 1
Neck, disorders of, 745–746 Nephrolithiasis, 897, 933, 948f, 948b, 1096 (NF1), 1127t, 1148t, 1239
Necroptosis, 47, 48b Nephronophthisis, 944, 944f, 944b Neurofibromatosis type 2, 1148t, 1239
TNF-mediated, 47f Nephropathy Neurokinin A, in inflammation, 92
Necrosis associated with NSAIDs, 932–933 Neurologic disorder, and systemic lupus
caseous, in immune granuloma, 100b–101b bile cast, 935 erythematosus, 222t
cell death and, 16 diabetic, 923 Neurologic sequelae, of metabolic
ischemic coagulative, 133b–134b gouty, 933 disturbances, 1292
liquefactive, 133b–134b light-chain cast, 934, 934f, 934t, 934b Neuromuscular diseases, 1217
morphologic changes in, 38f, 39–42, 40b membranous, 907t, 933 Neuromuscular junction
patterns of, 40–42 polyomavirus, 930, 930f antibody-mediated diseases of, 1225–1226
Necrotizing lesions, of nose and upper reflux, 930–931 diseases of, 1225–1226, 1226b
airways, 740 sickle-cell, 940 Neuromyelitis optica (NMO), 1272
Necrotizing papillitis, 1108b–1109b urate, 933, 933f Neuromyopathic paraneoplastic
Necrotizing pneumonia, 366b Nephrosclerosis, 492b–493b, 935– syndromes, 330
Negative selection, in immunologic 936, 935f, 935b–936b Neurons, 104, 134, 445–446
tolerance, 216 due to diabetes mellitus, 1111f reactions to injury, 1242
Negri bodies, 1266b, 1267f malignant, 936b, 938f Neuronal heterotopias, 1247
Neisseria gonorrhoeae, 364–365 Nephrotic syndrome, 116, 896, 898t, 911– Neuronal inclusions, 1242b
Neisseria meningitidis, 364 920, 920b Neuronal injury
Neisserial infections, 364–365 causes of, 912, 912t acute, 1242b
Nelson syndrome, 1072 due to focal segmental glomerulosclerosis, 914– reactions to, 1242
NEM, Nemaline myopathy 917, 916f–917f, 916b subacute and chronic, 1242b
Nemaline myopathy (NEM), 1231t due to HIV-associated nephropathy, 917, 917f Neuronal nitric oxide synthase (nNOS), 83
Neonatal cholestasis, 856, 859b due to membranoproliferative Neuronal storage diseases, 1289
major causes of, 856t glomerulonephritis, 917–918, 918f– Neuronal tumors, of CNS, 1298
Neonatal hepatitis, 856, 857f 919f, 918b Neuronopathies, 1220
morphology of, 857b due to membranous nephropathy, 912– Neuronophagia, 1243, 1265b
Neonatal respiratory distress 914, 913f, 913b Neuropathies, metabolic, hormonal, and
syndrome, 459–460, 459f–460f, 459b– due to minimal-change disease, 914, 914b, 915f nutritional, 1222–1223
460b pathophysiology of, 911 Neuropeptides, in inflammation, 92
Neoplasia, 267–338 Nerve, 1217–1240 Neurosyphilis, 376, 377b–
basic components of, 268 Nesidioblastosis, 1113b 378b, 1264, 1264b
characteristics of benign and malignant, 270– NETs, Neutrophil extracellular traps Neurotoxins, 347
276, 276t, 276b–277b Neural end organs, in skin, 1134 Neutral proteases, 83
differentiation and anaplasia, 270–273, 271f, 276t Neural tube defects, 1245–1246 Neutropenia, 586–587
local invasion, 273, 276t Neuritic plaques, in Alzheimer morphology of, 587b
metastasis, 273–276 disease, 1278b Neutrophil(s)
clinical aspects of, 328–336, 331b Neuroblastic tumors, 477–480 differentiation of, 585f
clinical manifestations of, 328–330 clinical course and prognostic features of, 478– in glomerular injury, 904–905
defined, 268 480, 479t, 480f in inflammation
desmoplasia, 268 morphology of, 478b acute, 80, 81t
host defense, evasion of Neuroblastomas, amplification of NMYC chronic, 100
antitumor effector mechanisms in, 311 gene in, 289f in innate immunity, 190
immune surveillance and escape as, 309–313, 313b Neuroborreliosis, 1264 in phagocytosis, 81–82
mechanism of, 311–313, 313f Neurodegenerative diseases, central nervous Neutrophil extracellular traps (NETs), 83–
tumor antigens in, 309–310, 310f system, 1273–1289, 1274t 84, 84f
local and hormonal effects of, 328 Alzheimer disease, 1275–1280, 1277f–1279f Neutrophilia, in inflammation, 102
molecular profiles of, 334–335 amyotrophic lateral sclerosis, 1287–1288, 1288f Neutrophils, adhesion and extravasation
nomenclature for, 268–270, 270t ataxia-telangiectasia, 1287 of, 676
scirrhous, 268 atypical parkinsonism syndromes, 1284–1285 Nevi, conjunctival, 1309
tumor markers for, 335–336, 336t corticobasal degeneration, 1284 Nevoid basal cell carcinoma syndrome
Neoplasm, defined, 268 dementia with Lewy bodies, 1283–1284 (NBCCS), 1147–1148, 1148t
Neovascular glaucoma, 1313f, 1314 Friedreich ataxia, 1287 Nevus flammeus, 519
Neovascularization, 499b–502b frontotemporal dementia, 1280 Nevus of Ota, 1310
Nephrin, 898–900, 900f Huntington disease, 1285–1286, 1286f Next-generation sequencing (NGS), 185–
Nephritic syndrome, 896, 898t, 906– of motor neurons, 1288–1289 187, 186f
911, 911b multiple system atrophy, 1284–1285, 1285b NF1., Neurofibromatosis type 1
Nephritis Parkinson disease, 1282–1284, 1283f NF2 gene, 1239
hereditary, 922, 922f, 923b Pick disease, 1280b, 1281f NGS, Next-generation sequencing
lupus, 923 progressive supranuclear palsy, 1284 NGU, Nongonococcal urethritis
tubulointerstitial, 926–927, 926t spinal and bulbar muscular atrophy (Kennedy NHEJ, Nonhomologous end joining
acute vs. chronic, 927 disease), 1289 NHLs, Non-Hodgkin lymphomas
drugs and toxins induced, 931–933, 932b–933b spinal muscular atrophy, 1289 Nickel, as carcinogen, 280t
Nicotinamide adenine dinucleotide Noncoding RNAs, alterations in, 143 Nutcracker esophagus, 757
(NAD), 419 Noncomedo ductal carcinoma in Nutmeg liver, 118f, 118b, 863b, 864f
Nicotinamide dinucleotide phosphate situ, 1053b–1054b Nutritional diseases, 433–450, 443b
(NADPH), 1108 Noncommunicating hydrocephalus, 1244 anorexia nervosa and bulimia, 435–436
Nicotine, 416 Nondisjunction, 165 cachexia, 435
Niemann-Pick disease Nonenzyme proteins, alterations of, 148 cancer in, 449
type C, 63, 158 Nongonococcal urethritis (NGU), 963 dietary insufficiency, 433
types A and B, 157–158, 158f, 158b Non-Hodgkin lymphomas marasmus, 434, 434f
Night blindness, 437–438 (NHLs), 592, 611t obesity, 444–449
Nipple clinical staging of, 615t protein energy malnutrition, 434
congenital inversion of, 1038 major types of, 595t vitamin deficiencies, 436–443, 443t
discharge, 1039, 1039f Nonhomologous end joining (NHEJ), 432 Nutritional imbalances, cell injury due to, 36
Paget disease of, 993, 1053b–1054b, 1055f Noninfectious vasculitis, 509–516 Nutritional status, tissue repair and, 108
supernumerary, 1038 Noninvasive thymomas, 632b–633b
Nitrates, as carcinogens, 449 Nonneoplastic cysts, 888
Nitric oxide (NO) Nonobstructive neonatal cholestasis, 856
cell injury due to, 53 Nonossifying fibroma, 1195, 1195f, 1195b O
in inflammation, 83 Nonpesticide organochlorines, 415 Obesity, 444–449, 448f, 449b
Nitric oxide synthase (NOS), 83 Nonproliferative breast and cancer, 278
Nitrosamides, in gastric carcinoma, 449 changes, 1042, 1042b, 1045t central/visceral, 444
Nitrosamines, 416 Nonproliferative diabetic retinopathy, 1321b clinical consequences of, 447–448
in gastric carcinoma, 449 Nonreceptor tyrosine kinase, 19 hyperinsulinemia, associated with, 448
Nitrous oxide, lung diseases due to, 692t oncogenes for, 288–289 insulin resistance, associated with, 448
NK-cell neoplasms, 605–607 Nonrhegmatogenous retinal pathogenesis of, 444
NKX2-5, in congenital heart disease, 535– detachment, 1320 Obligate intracellular bacteria, 381–382
536 Nonscarring alopecia, in systemic lupus Obliterative endarteritis, 1187b, 1203–1204
NLRs, NOD-like receptors erythematosus, 222t Obliterative portal venopathy, 862
NMO, Neuromyelitis optica Non-self antigens, 663–664 Obstructive lesions, of ureters, 954, 954t
NMYC gene, in neuroblastomas, 289f Nonseminomatous germ cell tumors Obstructive sleep apnea, 703
nNOS, Neuronal nitric oxide synthase (NSGCTs), 973 Obstructive uropathy, 945–947, 946f, 946b
NO, Nitric oxide Nonsense mutations, 668 Occluding junctions, 12
Nocardia, 363–364, 364b Nonspecific acute splenitis, 629 Occupational cancers, 280t
Nocardia asteroides, 364f Nonsteroidal antiinflammatory drugs Occupational health risks, 414–418, 414t
Nocardia brasiliensis, 363–364 (NSAIDs) Ochronosis, 65
NOD2 gene, autoimmune diseases and, 219t bleeding disorder due to, 667 OCs, Oral contraceptives
Nodes of Ranvier, 1217–1218 mechanism of action of, 88 Ocular changes, 149b
NOD-like receptors (NLRs), in innate Non-T cells, HIV infection of, 252 Ocular cicatricial pemphigoid, 1308
immunity, 191–192 Nontherapeutic agents, injury by, 423– Odontogenic cysts, 737–739, 737t
Nodular diabetic glomerulosclerosis, diffuse 426, 424t Odontogenic keratocyst (OKC), 737
and, 1111f Nontuberculous mycobacterial Odontogenic tumors, 738–739, 738t
Nodular fasciitis, 1211, 1211f, 1211b infections, 373 Odontoma, 739
Nodular glomerulosclerosis, 1108b–1109b Nonunion, 1185 Odynophagia, 758
Nodular hyperplasia(s) Normal-tension glaucoma, 1326 OI, Osteogenesis imperfecta
in liver, 865 Normoblasts, in hemolytic “Oil-droplet keratopathy,”, 1311
focal, 865b, 866f anemia, 638f, 638b OKC, Odontogenic keratocyst
prostatic, 976f, 977b Normochromic, normocytic anemia, 635 Older adults
Nodular sclerosis type, of Hodgkin Norovirus, and viral gastroenteritis, 794–795 heat stroke in, 428
lymphoma, 612b–614b, 614f NOS, Nitric oxide synthase vitamin D insufficiency in, 440
Nonalcoholic fatty liver disease Nose Olfactory neuroblastoma, 741, 742f
(NAFLD), 846–848, 847f, 848b disorders of, 739–740, 740f Oligodendrocytes, 1243
morphology of, 846b–847b inflammations of, 739–740 response to injury of, 1243
natural history of both phenotypes of, 847f necrotizing lesions of, 740 Oligodendroglioma, 1295–
Nonatopic allergy, 208 tumors of, 740–743 1296, 1296f, 1296b
Non-atypical hyperplasia, 1009f Nosocomial infection, 705 Oligohydramnios sequence, 455, 455f
Nonbacterial thrombotic Notch signaling, in angiogenesis, 107 Ollier disease, 1190
endocarditis, 564, 565f NOTCH2, in congenital heart disease, 536 Omega-3 fatty acids, 495–496
due to cancer, 330 NOTCH3 gene, 1257 Omphalocele, 754
Nonclassic inheritance, single-gene NRF2 gene, 680 Onchocerca volvulus, 399, 399f, 399b
disorders with, 173–180 NSAIDs, Nonsteroidal antiinflammatory Onchocerciasis, 399
Angelman syndrome as, 178–179 drugs Oncocytoma, 948
due to genomic imprinting, 178–179, 179b– NSGCTs, Nonseminomatous germ cell Oncogenes, 284–286, 285t, 286–290, 290b–
180b tumors 291b, 316t
due to gonadal mosaicism, 180 Nuclear DNA, organization of, 2f for growth factor receptors, 286–287
due to mutations in mitochondrial genes, 177– Nuclear factor κB (NF-κB), in innate for growth factors, 286
178 immunity, 191 for nonreceptor tyrosine kinases, 288–289
fragile X syndrome and fragile X tremor/ataxia Nuclear morphology, abnormal, 271–272 for receptor tyrosine kinase signaling
as, 174, 177b Nuclear receptors, 19 pathway, 287–288
Leber hereditary optic neuropathy, 177–178 Nuclear sclerosis, 1313–1314 Oncogenesis
Prader-Willi syndrome as, 178–179 Nucleosomes, 3 “two-hit” hypothesis of, 291
Noncoding DNA, 1–3 Nucleotide excision repair, 314 viral and bacterial, 327b
Oncogenic DNA viruses, 324–327 Osteitis deformans, 1182–1183, 1182f Oxyphil adenomas, in
Oncogenic RNA viruses, 324 Osteitis fibrosa cystica, 1181b hyperparathyroidism, 1094b–1095b
“Oncogenic” stress, 295 Osteoarthritis, 1198–1199, 1198f– Oxyphil cells, in parathyroid glands, 1093
Oncogenic viruses, tumor antigens produced 1199f, 1198b Oxytocin, 1067
by, 310 idiopathic/primary, 1198 Ozone (O3)
Oncology, 268 obesity and, 448 as air pollutant, 409
Oncoprotein-directed drugs, guiding therapy Osteoblasts, 1172, 1172f in greenhouse effect, 406
with, 333 Osteocalcin, 1172 Ozone layer, 409
Oncoproteins, 284, 286–290, 591 Osteochondritis, syphilitic, 377b–378b
Onion-bulb lesions, 1221, 1221f Osteoclasts, 1172–1173, 1172f
Onion-skin lesions, 225b–228b Osteocytes, 1172
Onycholysis, 1135t Osteogenesis imperfecta (OI), 1175– P
Open-angle glaucoma, 1314 1176, 1176t, 1177f PAF, Platelet activating factor
OPG, Osteoprotegerin subtypes of, 1177t Paget disease, 1182–1183, 1182f–
Opiates, abuse of, 424–425 Osteoid, 1171–1172 1184f, 1183b
Opportunistic infections, in AIDS, 255– Osteomalacia, 438, 440, 1180, 1182b extramammary, 993, 993b, 994f
256, 256t Osteomyelitis, 1185–1187, 1186f, 1186b of nipple, 1053b–1054b, 1055f
Opsonins, in inflammation, 80 Osteonecrosis, 1185, 1185f, 1185b Pagetoid spread, of urothelial carcinoma in
Opsonization Osteopenia, 1179–1180, 1182b situ, 959b–960b
in antibody-mediated hypersensitivity, 209– Osteopetrosis, 1176– Pain, due to pancreatic carcinoma, 893
210, 209f 1178, 1176t, 1177b, 1178f Pain crises, in sickle cell disease, 643–644
in inflammation, 74 Osteopontin, 1172 Palpable masses, of breast, 1039, 1039f
Optic nerve, 1306f, 1325–1327, 1327b Osteoporosis, 1179–1180, 1179f– Palpebral conjunctiva, 1308–1309
Optic neuritis, 1271 1180f, 1179t, 1180b PAMPs, Pathogen-associated molecular
Oral candidiasis, 733 clinical course of, 1180 patterns
Oral cavity, 731–739, 739b pathogenesis of, 1179–1180 Pancoast tumors, 721
diseases of teeth and supporting structures, 731 Osteoporosis-pseudoglioma Pancreas, 881–894
caries, 731 syndrome, 1176t acinar cell, 893–894
gingivitis, 731–732 Osteoprotegerin (OPG), 1173–1174 agenesis of, 882
periodontitis, 732 Otitis media, 744 annular, 881
due to infections, 733 Ouch-ouch disease, 413–414 congenital anomalies of, 881–882
deep fungal, 733 Outdoor air pollution, 408–410, 409t divisum, 881, 882f
with herpes simplex virus, 733 Oval cells, 104–105 ectopic, 881–882
oral candidiasis, 733 Ovarian cancers, oral contraceptives in, 422 endocrine, 881
due to systemic disease, 733–734, 734t Ovarian tumor(s), 1016–1028, 1017t, 1018f exocrine, 881
hairy leukoplakia, 733–734 Brenner, 1022, 1022f neoplasms, 888–894
inflammatory/reactive lesions of, 732–733, 733b choriocarcinoma, 1025 nonneoplastic cysts of, 888
aphthous ulcers, 732, 732f dysgerminoma, 1024–1025, 1025f, 1025b congenital, 888
fibrous proliferative, 732–733, 732f endometrioid, 1021, 1021b pseudo-, 888, 888f, 888b
odontogenic cysts and tumors, 737–739, 737t– germ cell, 1017t, 1023–1025, 1023f, 1025b– Pancreatic adenocarcinoma, invasive, 892t
738t 1026b Pancreatic carcinoma, 890–893, 893f
precancerous and cancerous lesions, 734–736 metastatic, 1028 clinical features of, 893
leukoplakia and erythroplakia, 734–735, 735f– mucinous, 1020–1021, 1020b, 1021f epidemiology and inheritance of, 891–892
736f, 735b serous, 1018–1020, 1019f–1020f, 1019b inherited predisposition to, 892t
squamous cell carcinoma, 735–736, 736b– Sertoli-Leydig cell, 1027–1028, 1027f, 1027b– morphology of, 892b–893b
737b, 737f–738f 1028b pathogenesis of, 891–892
Oral contraceptives (OCs), 422 sex cord-stromal, 1017t, 1026–1028, 1028b precursors to, 890–893
Oral ulcers, in systemic lupus surface epithelial-stromal, 1017t Pancreatic duct obstruction, 883, 883f
erythematosus, 222t teratomas, 1023–1024 Pancreatic endocrine neoplasm, 1114
Orbit, of eye, 1306–1307, 1307b type I, 1018 α-cell tumors (glucagonomas), 1114
Orchitis, 967, 967b–968b type II, 1018 VIPoma, 1114
mumps, 351b yolk sac, 1025 Zollinger-Ellison syndrome (gastrinomas), 1114
Orexigenic effect, 447 Ovaries, 1016–1028 Pancreatic enzymes, in pancreatitis, 882–
Organ dysfunction, in septic shock, 137 cortical inclusion cysts, 1018, 1018f 883
Organic materials, smoke from, 410 follicle and luteal cysts, 1016, 1016b Pancreatic intraepithelial neoplasia
Organic solvents, occupational health polycystic, 1016 (PanIN), 890, 890f–891f
risks, 414–415 stromal hyperthecosis, 1016 Pancreatic islet cells, 1098f
Organization Overexpressed cellular proteins, as tumor Pancreatic neuroendocrine tumors, 1113–
of fibrinous exudate, 93–94 antigens, 310 1114
of thrombi, 129, 129f Oxidant drugs, G6PD deficiency due hyperinsulinism, 1113–1114
Organochlorines, occupational health to, 640, 641f Zollinger-Ellison syndrome (gastrinomas), 1114
risks, 415 Oxidative stress Pancreatic polypeptide, 1097
Ormond disease, 954 cell injury due to, 52–53, 52t, 53f Pancreatic tissue, ectopic, 755
Orphan Annie eye nuclei, 1088b–1089b in emphysema, 680 Pancreatitis, 882–887
Orthopnea, in left-sided heart failure, 532– in primary acinar cell injury, 883 acute, 882–885, 885b–886b
533 Oxycodone, 424 clinical features of, 885
Osmotic demyelination disorder, 1272 Oxygen deprivation, cell injury due to, 36 interstitial, 885b
Ossification, intramembranous, 1173 Oxygen-derived free radicals, accumulation morphology of, 885b
Osteitis, fibrosa cystica, in of, cell injury due to, 52–53, 52t, 53f necrotizing, 885b
hyperparathyroidism, 1094b–1095b pathogenesis of, 882–884, 883f
vs. chronic, 886f morphology of, 1096b Pemphigus, 1159–1162, 1161f
autoimmune, 886, 886b–887b Parathyroid hormone, in erythematosus, 1161
chronic, 886–887, 887f, 887b–888b hyperparathyroidism, 1180 foliaceus, 1159f, 1160–1161, 1161f
clinical features of, 887 Parathyroid hormone-related protein vegetans, 1160
morphology of, 886b–887b (PTHrP), 1173 vulgaris, 210t, 1159–1160, 1159f–1160f
pathogenesis of, 886 in hypercalcemia, 329–330 Penis, 963–966
vs. acute, 886f Paratubal cysts, 1016 Bowen disease of, 965, 965f
and chronic alcoholism, 420 Parenchyma, 268 bowenoid papulosis of, 965
hemorrhagic, 885b Parenchymal injuries, of central nervous carcinoma of
hereditary, 884 system, 1249–1250 invasive, 965
Pancreatoblastoma, 894 Parenchymal organs, fibrosis in, 110, 111f in situ, 964–965, 965f, 966t, 966b
PanIN, Pancreatic intraepithelial neoplasia Parent-of-origin effects, 178 congenital anomalies of, 963
Panniculitis, 1166 Paretic neurosyphilis, 1264b inflammation of, 963–964
Pannus, 1201b Parkinson disease (PD), 1282–1284, 1283f lesions of, 965b–966b
Panophthalmitis, 1314–1315, 1315f Parkinsonism, 1282 tumors of, 964–966, 964f
Papillary carcinoma Paronychia, 360b Penumbra, 1253
in kidney, 949, 950b Parotid gland, mixed tumor of, 269f Peptic ulcer, 94
of thyroid, 1084–1092, 1088f Parotitis, mumps, 351b in Zollinger-Ellison syndrome
Papillary craniopharyngioma, 1074b Paroxysmal cold hemoglobinuria, 650 (gastrinomas), 1114
Papillary hidradenoma, of vulva, 993, 993f Paroxysmal nocturnal dyspnea, in left-sided Peptic ulcer disease (PUD), 770–
Papillary microcarcinoma, 1088b–1089b heart failure, 532–533 771, 770f, 770t–771t, 770b–771b
Papillary muscle dysfunction, due to Paroxysmal nocturnal hemoglobinuria Peptide display system, of adaptive
myocardial infarction, 551 (PNH), 91–92, 648–649, 649f immunity, 198–199
Papillary necrosis Pars plana, 1306f Peptide YY (PYY), in energy
in acute pyelonephritis, 928b–929b, 929f Pars plicata, 1306f balance, 444, 445f–446f, 447
causes of, 933t Partial thromboplastin time (PTT), 122, 662 Perforins, in T cell-mediated
Papillary transitional cell carcinoma, of Particulate matter, as air pollutant, 409 cytotoxicity, 215
ureters, 954f Parvovirus B19 Perfusion, poor, tissue repair and, 108
Papillary urothelial neoplasms of low perinatal infection with, 462, 462f Periapical granuloma, 738
malignant potential (PUNLMP), 959b– red cell aplasia due to, 661 Pericardial disease, 577–579
960b Passenger mutations, 282 Pericardial effusion, 577
Papilledema, 1326, 1326f Passive congestion, of liver, 863, 864f Pericardial spaces, in right-sided heart
Papilloma(s), 268 morphology of, 863 failure, 533b
of bladder, 959f, 959b–960b Passive transport, 9–10 Pericarditis, 552, 577–579, 577t, 578f
of breast, 1043b, 1044f Patau syndrome, 168f, 169 in systemic lupus erythematosus, 225b–228b
Papillomatosis, 1135t Patent ductus arteriosus (PDA), 538, 538f Pericytes, 487
Papillomatous epidermal coarctation of the aorta with, 540–541, 540f Periductal mastitis, 1040
hyperplasia, 1167b–1168b Patent foramen ovale, 537 Perifascicular atrophy, 1228b, 1229f
Papovavirus, 256 Pathogen-associated molecular patterns Perinatal brain injury, 1248
Papule, 1135t (PAMPs), 135–136 Perinatal infections, 356, 461–462
Papulosis, bowenoid, 965 in innate immunity, 191 Perineural invasion, in prostate
Paracortical hyperplasia, 589b Pathogenesis, 34 cancer, 979b–980b, 980f
Paracrine signaling, 17 Pathogenicity islands, 345–346 Perineurium, 1218
Paradoxical embolism, 536, 544 Pathology, 1 Periodontitis, 732
Parafollicular cells, 1075 clinical manifestations in, 34 Periostitis, syphilitic, 377b–378b
Paraganglioma, 746, 746f, 746b etiology or cause in, 34 Peripheral B-cell neoplasms, 597–604
Paraganglion system, 1126–1127 general, 33 morphology of, 597b
Parakeratosis, 1135t introduction to, 33–34 Peripheral blood granulocytes, 383f
Parallel sequencing, 185 molecular and morphologic changes in, 34 Peripheral giant cell granuloma, of oral
Paraneoplastic neuropathies, 1223–1224 pathogenesis in, 34 cavity, 732–733
Paraneoplastic pemphigus, 1161 systemic, 33 Peripheral lymphoid organs, 196–197
Paraneoplastic syndromes, 328– Pattern recognition receptors, in innate Peripheral nerves, diseases of, 1217–
330, 329t, 722 immunity, 191 1225, 1218f
Parasitic infections, 388–399 “Pauci-immune injury,” in microscopic Peripheral nerve injury, general types
African trypanosomiasis, 392, 393b polyangiitis, 514b of, 1218–1220
babesiosis, 390, 390b Pautrier microabscesses, 1151b Peripheral nerve sheath tumors, 1236–
Chagas disease, 393, 393b–394b PCBs, Polychlorinated biphenyls 1239, 1239b
cysticercosis and hydatid disease, 395– PCOS, Polycystic ovarian syndrome malignant, 1238
396, 396b PCV, Polycythemia vera morphology of, 1238b–1239b
lymphatic filariasis, 398, 398b–399b PD, Parkinson disease Peripheral neuropathies, 1225b
malaria, 388–390, 390b PDA, Patent ductus arteriosus anatomic patterns of, 1220
onchocerciasis, 399, 399b PDGF, Platelet-derived growth factor specific, 1220–1225
schistosomiasis, 397, 397b–398b PDX1 gene, 882 Peripheral ossifying fibroma, of oral
strongyloidiasis, 395, 395b PE, Pulmonary embolism cavity, 732
trichinosis, 396, 396b–397b Peau d'orange, 1056b–1058b Peripheral resistance, in blood pressure
Paratesticular tumors, 969 Peliosis hepatis, 862 regulation, 490–491
Parathyroid adenoma, 1093f–1094f Pelvic inflammatory disease (PID), 988– Peripheral T-cell lymphoma,
Parathyroid carcinomas, 1094b–1095b 989, 989b unspecified, 595t, 605, 605f
Parathyroid glands, 1093–1097 Pelvic pain syndrome, chronic, 956 Peripheral T-cell neoplasms, 605–607
clinical course of, 1096 PEM, Protein-energy malnutrition Peripheral tolerance, 217–218
Peritoneal cavity, 820 Phyllodes tumor, of breast, 1062– due to hypothalamic suprasellar tumors, 1074
infection of, 820 1063, 1062b–1063b, 1063f pituitary adenomas and hyperpituitarism, 1067–
inflammatory disease of, 820, 820b Physical agents 1072
sclerosing retroperitonitis of, 820 cell injury due to, 36 ACTH cell (corticotroph), 1071–1072
tumors of, 820 injury by, 426–433 gonadotroph (LH-producing and FSH-producing)
Peritoneal mesothelioma, 727 mechanical, 426–427 adenomas, 1072
Peritoneal spaces, in right-sided heart thermal, 427–428 nonfunctioning (silent variants, null-cell)
failure, 533b toxicity of chemical and, 407–408 adenomas, 1072
Perivascular amyloidosis, 663 Physical defects of the uterus, 1029 prolactinomas, 1070f
Periventricular leukomalacia, 1248, 1249f Physical forces, neuropathies caused thyrotroph (TSH-producing), 1072
Permanent tissues, 104 by, 1224 Pituitary dwarfism, 1073
Pernicious anemia, 210t, 651t, 652–653 Physical injury, inflammation due to, 74 Pituitary gland, 1066–1074
clinical features of, 654 Physiologic jaundice of the newborn, 853 carcinoma, 1072
incidence of, 653 Physis, 1173 normal, 1067f
morphology of, 654b PI3K mutations, 287–288 Pituitary syndromes, 1073–1074
pathogenesis of, 653–654 PI3K/AKT pathway, in endometrial Pituitary tumors, genetic alterations
Peroxisome proliferator-activated receptors carcinoma, 1009 in, 1069t
(PPARs), 408, 437 PI3K/AKT signaling, 300 PKU, Phenylketonuria
Peroxisomes, 7 Pick bodies, 1280b Placenta, 1028, 1029f–1030f, 1032b–1033b
Peroxynitrite (ONOO-) Pick cells, 1280b preeclampsia and eclampsia, 1031–1033, 1031f–
cell injury due to, 52t Pick disease, 1280b 1033f
in phagocytosis, 83 Pickwickian syndrome, 448 Placental abnormalities, in fetal growth
Persistent diarrhea, 256 PID, Pelvic inflammatory disease restriction, 458–459
Persistent lymphedema, 398b–399b, 399f PIF, see Proteolysis-inducing factor Placental-fetal transmission, 341
Persistent truncus arteriosus, 538 PIGA, Phosphatidylinositol glycan Placental implantation, abnormalities
Pertussis, 365, 365b, 366f complementation group A gene of, 1031
Petechiae, 125f Pigeon breast deformity, 440b–442b Placental infections, 1031, 1031f
Peyronie disease, 964, 1211 Pigeon breeder's lung, 698 Placental site trophoblastic tumor
Phacolysis, 1314 Pigment stones, 873t, 874f (PSTT), 1035
Phagocytes, killing by, resistance to, 343 morphology of, 874b Plague, 366–367, 367b
Phagocyte oxidase, 82–83 Pigmentary glaucoma, 1314 Plaque(s), 1135t
Phagocyte receptors, in inflammation, 80 Pigmentation disorders, 1135–1142 dental, 732
Phagocytosis, 10–11, 15 dysplastic nevi, 1137–1138 jaune, 1250f, 1250b
in antibody-mediated hypersensitivity, 209–210 freckle (ephelis), 1135 Plasma cells, in chronic inflammation, 99
complement system in, 91, 91f lentigo, 1136 Plasma cell leukemia, 608b–609b
discovery of, 73 melanocytic (pigmented) nevus (mole), 1136– Plasma cell neoplasms, 592, 611b
frustrated, 84 1137 and related disorders, 607–611
in inflammation, 80–81, 82f melanoma, 1139–1142 Plasma-derived mediators, 85–86
Phagolysosome, 82–83 Pigmented nevus, 1136–1137 Plasma membrane
Phagolysosome function, defects in, 241 Pigmented villonodular synovitis, 1207 damage, 51
Phagosome, 80–81 Pigments, intracellular accumulation of, 64– movement of small molecules and larger
Pharyngitis, 740 65 structures across, 10f
Phenotypic sex, 173 Pilar leiomyomas, 1213 organization and asymmetry of, 8f
Phenylketonuria (PKU), 465–466, 466f Pili, 346 protection and nutrient acquisitions, 8–11
Pheochromocytoma(s), 1127– Pilocytic astrocytomas, 1325 Plasma osmotic pressure, reduced, edema
1129, 1128f, 1128b Pilomatricoma, 1144 due to, 116
clinical course of, 1128–1129 Pilomatrixomas, 1144b–1145b Plasma protein-derived mediators, of
Philadelphia chromosome, 317 PIN, Prostatic intraepithelial neoplasia inflammation
Phimosis, 963 Pinealomas, 1131 complement system as, 90–92
Phlebothrombosis, 128b–129b, 130, 517 Pinguecula, 1309 kinins, 92
Phosphatase and tensin homologue (PTEN) Pink puffers, 682 products of coagulation, 92
gene, 287–288, 298–299 Pink tetralogy, 539 Plasmablast, 195
in endometrial carcinoma, 1007 Pinocytosis, 11 Plasmacytoma, solitary, 595t
in endometrial hyperplasia, 1007 Pipe-stem fibrosis, 397b–398b, 398f Plasmapheresis, 705
Phosphatidylinositol, 8 Pituicytes, 1067 Plasmin, in fibrinolysis, 122–123
Phosphatidylinositol glycan Pituitary adenomas, 1067–1073, 1069f– Plasminogen, in fibrinolysis, 122–123
complementation group A gene 1070f Plasminogen activators, in fibrinolysis, 122–
(PIGA), 648 ACTH cell (corticotroph), 1071–1072 123
Phosphatidylserine, 9 anterior, 1072 Plasminogen activator inhibitors (PAIs), 126
Phospholipid breakdown, increased, cell classification of, 1068t Plasmodium falciparum, 388, 389f–
injury due to, 51 clinical course of, 1070 390f, 390b
Phospholipid synthesis, decreased, cell gonadotroph (LH-producing and FSH- Platelet(s)
injury due to, 51 producing) adenomas, 1072 decreased production of, 663, 664t
Phosphorus homeostasis, vitamin D in, 440 morphology of, 1069b–1070b decreased survival of, 663–664, 664t
Photosensitivity, in systemic lupus nonfunctioning, 1072 defined, 119–120
erythematosus, 222t prolactinomas, 1070f differentiation of, 585f
Phrygian cap, of gallbladder, 872, 873f surgery, 1073 in glomerular injury, 904
Phthisis bulbi, 1328 thyrotroph (TSH-producing), 1072 in hemostasis, 119–120
Pituitary apoplexy, 1067, 1073 sequestration of, 664, 664t
Pituitary disorder(s)
Platelet activating factor (PAF), in due to Klebsiella pneumoniae, 707 Polyradiculoneuropathies, 1220
necrotizing enterocolitis, 460–461 due to Legionella pneumophila, 707 POMC, Pro-opiomelanocortin
Platelet activation, in due to Moraxella catarrhalis, 707 Pompe disease, 163f, 1234
hemostasis, 120, 120b, 122 due to Mycoplasma pneumoniae, 707–709 Porphyria, 1163–1164, 1164f
Platelet adhesion, 120, 120f, 120b due to Pseudomonas aeruginosa, 707 Port wine stain, 519
Platelet aggregation, 120, 120f, 120b due to Staphylococcus aureus, 707 Portal hypertension, 827–830
in thrombotic microangiopathies, 937–938 due to Streptococcus pneumoniae, 706 consequences of, 830f
Platelet contraction, 120 fibrosing location and causes of, 829t
Platelet counts, 662 cryptogenic organizing, 690, 691f Portal system, in right-sided heart
Platelet function(s) nonspecific interstitial, 690, 690b failure, 533b
defective, bleeding disorders related to, 666– hospital-acquired, 706t, 711 Portal vein obstruction and thrombosis, 861–
667 idiopathic chronic eosinophilic, 698 862
tests of, 663 in immunocompromised host, 706t, 714, 714t Portopulmonary hypertension, 830
Platelet inhibitory effects, of lobar, 707f–708f, 707b–709b Portosystemic shunts, 829–830
endothelium, 123 lung abscess, 706t, 711–712, 711b–712b Posterior fossa anomalies, 1247
Platelet number, reduced, bleeding related necrotizing, 706t Posterior subcapsular cataract, 1313–1314
to, 663–666, 664t usual interstitial, 690f Posterior synechiae, 1314–1315
Platelet plug, 118 Pneumonic plague, 367b Postinfectious glomerulonephritis, 906–907
Platelet-activating factor (PAF), 207, 684 PNH, Paroxysmal nocturnal hemoglobinuria Postmenopausal osteoporosis, 1179f, 1180
in inflammation, 92 Podocytes, 898, 899f, 901b Postmortem clots, 128b–129b
Platelet-derived growth factor POEMS syndrome, 1224 Postpolio syndrome, 1266
(PDGF), 20t, 21 Poison, definition of, 407 Postrenal azotemia, 896–897
Pleiotropism, 144 Polarity, loss of, in neoplasia, 272 Poststreptococcal
Pleomorphic adenoma, 269 Poliomyelitis, 351, 1266, 1266b glomerulonephritis, 211t, 906–907
of salivary glands, 748–749, 748b, 749f Poliovirus infection, 351 Posttranscriptional silencing, 4
Pleomorphic liposarcoma, 1209b Pollution, environmental, 408–414 Posttranslational modifications, 154
Pleomorphic rhabdomyosarcoma, 1212b air, 408–410 Posttraumatic hydrocephalus, 1252
Pleomorphism, in neoplasia, 271 metals, 411–414 Potocytosis, 11
Pleural effusion, 725 Polonium 214 and 218, as carcinogens, 433 Pott, Percival, 320–321
inflammatory, 725 Polyarteritis Pott disease, 371b–373b, 1186
noninflammatory, 725 nodosa, 211t, 234, 513, 513f, 513b Potter sequence, 455, 455f
in right-sided heart failure, 533b cerebral infarction due to, 1254 Poverty, and malnutrition, 433
Pleural plaques, in asbestos, 695f, 695b Polychlorinated biphenyls (PCBs), PPROM, Preterm premature rupture of
Pleural spaces, in right-sided heart occupational health risks, 415 placental membranes
failure, 533b Polycyclic hydrocarbons, occupational Prader-Willi syndrome, 178–179, 179f
Pleuritis, hemorrhagic, 725 health risks, 415 Pre-B cells, 243–244
Plexiform neurofibromas, 1237, 1237b– Polycystic kidney disease Precursor B-cell neoplasms, 594–597
1238b, 1238f autosomal dominant (adult), 941–943, 941f– Precursor lesions, 280
Plummer syndrome, 1084 943f, 941t, 942b Preductal coarctation, 541b
Plummer-Vinson syndrome, 658, 757 autosomal recessive Preeclampsia, 458, 864
Pluripotency, of hematopoietic stem (childhood), 941f, 941t, 943–944, 943b morphology of, 864b
cells, 584 Polycystic ovarian syndrome (PCOS), 1016 Pregnancy
PML, Progressive multifocal Polycythemia, 662 and breast cancer, 1046–1047
leukoencephalopathy absolute, 662 breast during, 1037–1038
Pneumatosis intestinalis, in necrotizing pathophysiologic classification of, 662t hepatic disease associated with, 864–865
enterocolitis, 461, 461f relative, 662 toxemia of, 458
Pneumoconioses, 415, 691–695, 695b–696b Polycythemia vera (PCV), 624– Pregnancy disorder(s), 1029–1030
coal workers', 692, 692b–693b, 693f 625, 624f, 662 choriocarcinoma, 1034–1035, 1035f, 1035b
Pneumocystis infections, 386, 386f morphology of, 624b ectopic pregnancy, 1029–1030
Pneumocystis jiroveci pneumonia, 255 Polydactyly, 454f gestational trophoblastic disease, 1033–1035
Pneumonia, 705–706 Polyglucosan bodies, 1243 hydatidiform mole, 1033–1034, 1034f, 1034b
acute, 711b Polyglutamine diseases, 1286–1287 of placental implantation, 1031
eosinophilic, with respiratory failure, 698 Polykaryons, 348 placental infections, 1031, 1031f
aspiration, 706t, 711 Polymerase chain reaction (PCR) test, for placental site trophoblastic tumor, 1035
bacterial, 707b–709b, 708f infectious agents, 351 preeclampsia and eclampsia, 1031–1033, 1032f–
bronchopneumonia, 707f, 707b–709b Polymicrogyria, 1247 1033f
chronic, 706t, 712–713 Polymorphic markers, 184, 184f spontaneous abortion, 1029
blastomycosis, 712–713, 713f, 713b Polymorphisms, single nucleotide, 183 twin placentas, 1030–1031, 1030f
coccidioidomycosis, 713, 713b, 714f Polymyositis, 1229, 1230b Pregnancy luteoma, 1028
histoplasmosis, 712, 712b, 713f Polyneuropathies, 1220 Prematurity, 457–461
community-acquired Polyol pathways, intracellular necrotizing enterocolitis with, 460–461, 461f
bacterial, 706–709, 706t hyperglycemia and disturbances in, 1108 neonatal respiratory distress syndrome
viral, 709–710, 710b Polyomavirus nephropathy, 930, 930f with, 459–460, 459f–460f
complications of, 707b–709b Polyp(s), 268 retinopathy of, 460
desquamative interstitial, smoking- colonic, 268f Premutations, in fragile-X syndrome, 175–
related, 699, 699f, 699b fibroepithelial, of ureters, 954 176
due to Haemophilus influenzae, 706–707 stomach, 773–779 Prerenal azotemia, 896–897
due to human coronaviruses, 710 fundic gland, 773, 773b–774b in left-sided heart failure, 533
due to human metapneumovirus, 710 inflammatory and hyperplastic, 773, 773b, 774f Pressure atrophy, 60
due to influenza virus, 709–710 Polypoid cystitis, 956–957 Pressure-overload hypertrophy, 530
Pressure sores, 110, 111f with atypia, 1044–1045, 1045t, 1045b in immediate hypersensitivity, 207
Preterm, 458 without atypia, 1042–1044, 1043b, 1045t Prothrombin gene mutation, and
Preterm premature rupture of placental Proliferative diabetic retinopathy, 1321b thrombosis, 127
membranes (PPROM), 458 Proliferative vitreoretinopathy, 1319–1320 Prothrombin time (PT), 122, 662
Pretibial myxedema, 1081 Pro-opiomelanocortin (POMC), 328, 1124 Proto-oncogenes, 284, 286, 290b–291b, 316
Primary acinar cell injury, 883, 883f Propagation, of thrombi, 129 Protozoa, 388t
Primary acute adrenocortical Proptosis, 1306–1307 sexually transmitted infections, 400t
insufficiency, 1122 Propylthiouracil, 1075 Protozoal diseases, of CNS, 1268–1269
Primary adrenocortical neoplasms, 1116b– Prostacyclin (PGI2) Protozoal infections, 388–394
1117b in hemostasis, 123 Proud flesh, 111
Primary angle-closure in inflammation, 88 PrP, Prion protein
glaucoma, 1313f, 1314 Prostaglandins, in inflammation, 86–87 PRSS1 gene, pancreatitis, 884, 884t
Primary autoimmune pharmacologic inhibitors of, 88 PSA, Prostate-specific antigen
adrenalitis, 1124f, 1124b Prostaglandin D2, 684 P-selectin, in inflammation, 78, 78t
Primary biliary cirrhosis, 857– in immediate hypersensitivity, 207 Pseudo-aneurysm, 504–505
858, 858f, 859b Prostate, 975–983 Pseudoangiomatous stromal hyperplasia, of
main features of, 857t benign enlargement of, 976–977, 976f– breast, 1061–1062
morphology of, 857b–858b 977f, 976b–977b Pseudoarthrosis, 1185
Primary center, of ossification, 1173 carcinoma of, 982b Pseudocysts, pancreatic, 888, 888f, 888b
Primary ciliary dyskinesia, 687 colloid carcinoma of, 982 Pseudoepitheliomatous
Primary CNS lymphoma, 1299–1300, 1300b inflammation of, 975–976 hyperplasia, 367b, 1149b–1150b
Primary effusion lymphoma, 257, 601 normal anatomy and histology of, 975, 975f Pseudo-gout, 1205–1206, 1207f
Primary gout, 1204 tumors of, 977–983, 979f–980f, 982t Pseudohermaphroditism, 173
Primary hepatolithiasis, 855, 859b Prostate cancer, 978f Pseudohypertrophy, 1233
morphology of, 855b Prostate-specific antigen (PSA), 981–982 Pseudohypoparathyroidism, 1097
Primary hyperparathyroidism, 1181 Prostatic hyperplasia, benign or Pseudomonas
Primary hyperplasia, in nodular, 976–977, 976f, 977b infection, 366, 366b
hyperparathyroidism, 1094b–1095b Prostatic intraepithelial neoplasia (PIN), 979 in pyogenic osteomyelitis, 1185–1186
Primary immune deficiency Prostatitis, 975–976 Pseudomonas aeruginosa, 366
diseases, 243f, 246b acute bacterial, 975 Pseudomonas vasculitis, 366f
Primary/immunocyte-associated chronic Pseudomyxoma peritonei, 274–
amyloidosis, 607 abacterial, 975 275, 1021, 1021f
Primary immunodeficiencies, 240–246 bacterial, 975 Pseudophakic bullous keratopathy, 1312
Primary malnutrition, 433 granulomatous, 975–976 Psoriasis, 213t, 1157, 1157f, 1157b–1158b
Primary myelofibrosis, 626–627, 626f Prosthetic valves, complications of, 565– PSP, Progressive supranuclear palsy
morphology of, 626b 567, 566t PSTT, Placental site trophoblastic tumor
Primary open-angle glaucoma, 1314 Proteases, 680 PT, Prothrombin time
Primary Raynaud phenomenon, 516 Protease-activated receptors (PAR-1, PAR- Pterygium, 1309
Primary sclerosing cholangitis, 858– 4), 120 PTHrP, Parathyroid hormone-related protein
859, 859f, 859b Protease-antiprotease imbalance, in PTT, Partial thromboplastin time
main features of, 857t emphysema, 680 PUD, Peptic ulcer disease
morphology of, 858b Proteasomes, 7, 14–15 Puerperal infections, pelvic inflammatory
Primary spongiosa, 1173, 1173f degradation of, 14f disease, 988
Prinzmetal variant angina, 543 Protective antigen, in anthrax, 363 Pulmonary atresia, congenital, 541
Prion diseases, 1273–1275, 1275f–1276f Protein aggregation, in Alzheimer Pulmonary congestion, 118b
Prion protein (PrP), 1273 disease, 1277f Pulmonary edema, in heart failure
Pro-apoptotic Bcl family, 45 Protein-aggregation diseases, 64 left-sided, 533
Pro-B cells, 243–244 Protein C, 123–124 right-sided, 533b
Progenitor cells, liver regeneration Protein-calorie deficiencies, 36 Pulmonary embolism (PE), 131, 517
from, 104–105 Protein-coding genes, alterations in, 143 Pulmonary infarction, 700–702, 701f
Progesterone receptors, in breast Protein-energy malnutrition Pulmonary stenosis, congenital, 541
carcinoma, 1060 (PEM), 434, 435b Pulmonary venous connection, total
Programmed cell death, 42 in upper income world, 435 anomalous, 538
evasion of, 295 Protein kinase A regulatory subunit 1 PUNLMP, Papillary urothelial neoplasms of
Progressive bulbar palsy, in amyotrophic (PRKAR1A) gene, in pituitary low malignant potential
lateral sclerosis, 1288 tumors, 1069t Pupil, 1306f
Progressive multifocal leukoencephalopathy Protein kinase C (PKC), activation of, 1108 Pupillary block, 1314
(PML), 1267–1268, 1268f, 1268b Protein-protein links, 53 Pure red cell aplasia, 661, 661b–662b
Progressive muscular atrophy, in Protein reabsorption droplets, in proximal Purkinje network, 528
amyotrophic lateral sclerosis, 1288 renal tubules, 63, 63f Purpura(s), 125
Progressive supranuclear palsy Protein S, 123–124 Henoch-Schönlein, 663
(PSP), 1284, 1284b Protein tyrosine phosphatase-22 (PTPN22) thrombocytopenic
Pro-growth signaling pathways, 1140 gene, 1078–1079, 1202 immune
Proinflammatory cytokines, 448 autoimmune diseases and, 219t acute, 665
Pro-inflammatory effects, in hemostasis, 122 in autoimmunity, 219 chronic, 664–665
Prolactin, 1070b Proteinopathies, 64, 1242 thrombotic, 665–666, 666t
Prolactinomas, 1070f Proteins, intracellular accumulation of, 63– Pus, 75, 94
Prolactin-secreting lactotroph 64 Pustular psoriasis, 1157b–1158b
adenomas, 1070 Proteinuria, asymptomatic, 896 Pustule, 1135t
Proliferative breast disease Proteoglycans, 23–24, 24f
Pyelonephritis, 927– in cell injury, 50f, 52–53, 52t, 53f and systemic lupus erythematosus, 222t
931, 927f, 931b, 1108b–1109b in inflammation, 88 vascular, 935–940
acute, 928–930, 928f–929f, 928b–929b in leukocyte-mediated tissue injury, 84 diffuse cortical necrosis, 939f, 939b
chronic, 930–931, 930f–931f, 930b–931b in phagocytosis, 82–83 renal infarcts, 940, 940b
due to ureteral obstruction, 954 in toxicology, 408 Renal failure
xanthogranulomatous, 930b–931b Reactive stroma, 268 chronic, 896–897, 898t
Pyloric stenosis, 755 Real-time PCR, 182 in hyperparathyroidism, 1096
Pyogenic bacteria, 94 Recanalization, of thrombi, 129, 129f Renal glomerulus, 1110f
Pyogenic granulomas, 520 Receptors, defects in, 148 Renal hyaline arteriolosclerosis, 1110f
of oral cavity, 732, 733f Receptor cross-linking, 17 Renal infarcts, 940, 940b
Pyogenic meningitis, 1262, 1262f Receptor editing, 216 Renal medulla, cystic diseases of, 944
Pyogenic osteomyelitis, 1185–1186 Receptor-mediated and fluid-phase Renal osteodystrophy, 1096, 1181–
Pyosalpinx, 989f, 989b uptake, 10f, 11 1182, 1182f, 1182b
Pyrin, in amyloidosis, 262 Receptor-mediated endocytosis, 11 Renal papillary adenoma, 948, 948b
Pyrogens, 101–102 Receptor-mediated signaling, 18f Renal pelvis, urothelial carcinoma of, 951–
Pyroptosis, 47, 48b Receptor tyrosine kinases (RTKs), 19 952, 951f
activity, 300 Renal sodium, excretion, insufficient, 492
Recognition, 72 Renal tubular defects, 897
Recombination activating genes (RAG), 194 Renin, in blood pressure regulation, 491
Q Recruitment, of leukocytes, 72 Renin-angiotensin system, in blood pressure
Q fever, 706t Recurrent thromboemboli, 702 regulation, 491, 491f
Quorum sensing, 346 Red cedar dust, asthma due to, 692t Renovascular hypertension, 492
Red cell aplasia, pure, 661 Repair, 71–113
Red cell count, adult reference range by connective tissue deposition, 105–108
R for, 637t cutaneous wound healing and pathologic aspects
Rabies, 1266–1267, 1266b Red cell distribution width, 635, 637t of, 111b
Race/ethnicity, and breast cancer, 1046 Red cell enzyme defects, hemolytic disease by regeneration, 105b
“Rachitic rosary,”, 440b–442b due to, 640, 640f–641f by scar formation, 108b
Radial scar, of breast, 1043b, 1044f Red cell indices, 635, 637t Reperfusion, of myocardial infarction, 549–
Radial sclerosing lesion, of Red cell trauma, hemolytic anemia due 550, 550f
breast, 1043b, 1044f to, 650, 650f Reperfusion injury, 549, 550f
Radiation, 428–429 “Red neurons,”, 1242b Replicative potential, limitless, in
cancer risks from exposures to, 432–433 Reduction-oxidation reactions, 52 cancer, 284, 305b
CNS effects of, 1292–1293 Reed-Sternberg cells, 611, 612b– Replicative senescence, 67–68, 67f–68f
ionizing 614b, 613f, 615f RER, Rough endoplasmic reticulum
biologic effects of, main determinants of, 429– in Hodgkin lymphoma, 258 Resident glomerular cells, in glomerular
430, 429f–430f, 430t Reflux nephropathy, 930–931 injury, 904–905
injury produced by, 428–433, 430b–431b, 433b Regenerating myofibers, 1228 Resolution, 108
units of, 429 Regeneration, 103, 103f Resorption atelectasis, 675
Radiation carcinogenesis, 323, 323b cell and tissue, 103–105 Resorption pit, 1172–1173
Radiation cystitis, 955b–956b liver, 104–105, 104f Respiratory bronchiole, 673–674
Radiation pneumonitis, 696 Regenerative medicine, 29–30 Respiratory burst, in phagocytosis, 82–83
Radiation retinopathy, 1322–1323 Regulated and normal T-cell expressed and Respiratory diseases, climate change
Radioallergosorbent test (RAST), 683 secreted (RANTES), 90 and, 406
Radon Regulation, of response, 72 Respiratory distress syndrome (RDS), in
as carcinogen, 280t, 433 Regulatory genes, in cancer, 319t newborn, 459, 459f–460f
in indoor air pollution, 410 Regulatory T cells (Tregs), 217 Respiratory tract, infections via, 340t, 341
RAG, Recombination activating genes induction of, in immune evasion, 312 Response to injury, vascular wall, 487–489
Ragged red fibers, 1235f, 1235b Regurgitation theory, of endometriosis, 1005 Restriction fragment length analysis, 182
RANKL, 1173–1174 Relapsing febrile nodular panniculitis, 1166 Restrictive cardiomyopathy, 574, 574b
in giant cell tumor, 1193 Remodeling process, 1173 RET gene, in thyroid, 1087
RANTES, Regulated and normal T-cell Removal, of stimulus for inflammation, 72 Reticular hyperplasia, 589b
expressed and secreted Renal artery stenosis, 936–937, 936b–937b Reticulocyte count, adult reference range
Rapidly progressive glomerulonephritis Renal atherosclerosis, 1108b–1109b for, 637t
(RPGN), 896, 909–911, 909t, 910f, 910b Renal calculi, 947–948, 947t, 948b Reticulocytosis, 637
RARs, Retinoic acid receptors Renal cell carcinoma, 948–951, 949f–951f in hemolytic anemia, 638b
RAS oncogene, 287–288 classification of, 949–950 Reticuloendothelial system, in chronic
RAST, Radioallergosorbent test clinical features of, 950–951 inflammation, 97
Rathke cleft cyst, 1073 epidemiology of, 948–949 Retina, 436, 1306f, 1318–1325, 1324b–
Raynaud phenomenon, 516–517, 516f morphology of, 950b, 951f 1325b
in systemic sclerosis, 233 Renal cortex, 1110f Retinal detachment, 1319–1320, 1319f
RB, in osteosarcoma, 1188 Renal diseases, 896 Retinal pigment epithelium (RPE), 1319
RB tumor suppressor gene, 293– atheroembolic, 939, 940f Retinal vasculitis, 1322–1323
294, 294f, 294b atherosclerotic ischemic, 939 Retinitis, 1324
RDS, Respiratory distress syndrome clinical manifestations of, 896–897, 897b Retinitis pigmentosa, 1319, 1324
Reactive arthritis, 211t, 1203 congenital anomalies, 940–941 Retinoblastoma, 1324–1325, 1325f
Reactive lymphadenitis, 76 agenesis, 940 pathogenesis of, 293f
Reactive nodules, of vocal cords, 743, 743f ectopic kidneys, 940–941 Retinoic acid, 436
Reactive oxygen species (ROS) horseshoe kidneys, 941 Retinoic acid receptors (RARs), 437
in alcohol metabolism, 419 hypoplasia, 940 Retinoic X receptor (RXR), 408
Retinoids, 436 RXR, Retinoic X receptor Scurvy, 442
metabolic effects of, 437 RYR1, mutations of, 1236 bleeding disorders due to, 663
Retinol, 436 Sebaceous adenoma, 1144, 1144b–1145b
Retinopathy, of prematurity, 460, 1322– Sebaceous carcinoma, 1145
1323 of eyelid, 1308, 1308f, 1308b
Retrolental fibroplasia, 1322–1323 S Seborrheic dermatitis, 1158, 1158b
Retroviral syndrome, acute, 253–254 S. aureus toxins, 360, 360f Seborrheic keratosis, 1142, 1142b–
Rhabdomyoma, cardiac, 579–580, 580b S-100, 1128b 1143b, 1143f
Rhabdomyosarcoma, 272f, 1212, 1212f Saccular aneurysms, 505, 1258, 1259f Secondary angle-closure glaucoma, 1314
embryonal, of bladder, 962 ruptured, 1258–1260 Secondary center, of ossification, 1173
Rhegmatogenous retinal detachment, 1319– unruptured, 1259f, 1259b Secondary eosinophilia, 698
1320 Sacrococcygeal teratomas, in infants and Secondary gout, 1204
Rhesus immune globulin (RhIg), 462–463 children, 476–477, 476f Secondary hyperparathyroidism, 1181
Rheumatic fever, 560–563, 561b–562b Salpingitis Secondary immunodeficiencies, 246
Rheumatic heart disease, 560– chronic, 989f, 989b causes of, 246t
563, 561f, 561b–562b suppurative, 1015 Secondary open-angle glaucoma, 1314
Rheumatic mitral valve stenosis, and acute, 989b Secondary osteoarthritis, 1198
thrombosis, 126 tuberculous, 1015 Secondary pulmonary alveolar
Rheumatoid arthritis, 213t, 229, 691, 1199– Salpingo-oophoritis, 989b proteinosis, 700
1202, 1199f–1202f, 1201b Salt retention, edema due to, 116 Secondary Raynaud phenomenon, 516
autoantibodies in, 222t Salt-wasting syndrome, 1121 “Second-hand smoke,”, 415
HLA alleles and, 219t SAM, Sever acute malnutrition Secretagogues, 206
Rheumatoid factor, 1200 Sanger sequencing, 181 Secretory carcinoma, 1056b–1058b, 1059f
Rheumatoid vasculitis, 515–516 SAP, SLAM-associated protein Sedentary lifestyle, diabetes mellitus
RhIg, Rhesus immune globulin Sarcoidosis, 101 and, 1103
Rhinitis, chronic, 739 Sarcolemma, 1225 Seeding, of body cavities and surfaces, 274–
Rhinocerebral mucormycosis, 388b Sarcoma(s), 269, 1209, 1209t 275
Rhodopsin, 436–437 of bladder, 962 Selectins, in inflammation, 78, 78t
Richter syndrome, 599 botryoides, 1212b Self antigens, abnormal display of, 218
Rickets, 438, 440, 1180 of breast, 1063 Self-imposed dietary restriction, and
Rickettsial infections, 382 cardiac, 579 malnutrition, 433
Riedel thyroiditis, 1081 Sarcomeres, of myocardium, 528 Self proteins, citrullination of, 1200
Right bundle branches, 528 Sarcoplasmic reticulum, 13 Self-renewal
Right-sided heart failure, 533–534 SARS-CoV-2 (COVID-19), 353, 401t, 710 in cancer, 304, 305f
Right-sided hypertensive heart Satellite cells, 104 of hematopoietic stem cells, 584
disease, 556, 556f, 556t Scale, 1135t Self-tolerance
Right-to-left shunts, 536, 538–540, 539f Scar, 105 in B cells, 224
due to persistent truncus arteriosus, 538 hypertrophic, 110 in immunologic tolerance, 216
due to tetralogy of Fallot, 538–539, 539f Scar formation, 103, 103f Semilunar valves, 528
due to total anomalous pulmonary venous repair by, 108b Seminoma, 970, 970f–971f, 970b
connection, 538 steps in, 105–106, 105f spermatocytic, 970–971, 971b
due to transposition of the great arteries, 539– Scarlet fever, 361b Senescence
540, 539f–540f SCAs, Spinocerebellar ataxias evasion of, 303, 304f
due to tricuspid atresia, 538 Scavenger receptors, in inflammation, 80 p53-induced, 295
Right ventricular infarction, 551 SCC, Squamous cell carcinoma Senile atrophy, 60
RIG-like receptors (RLRs), 192 SCD, Sudden cardiac death Senile cardiac amyloidosis, 263
Ring chromosome, 165, 166f Schiller-Duval body, in yolk Senile osteoporosis, 1179, 1179f
RLRs, RIG-like receptors sac, 1025, 1025f Senile systemic amyloidosis, 263
RNA analysis, 185 Schistosoma Sensorimotor neuronopathy, 1223–1224
Robertsonian translocation, 166, 166f haematobium infection, 397f, 397b– Sentinel lymph node, biopsy of, for breast
Rocky Mountain spotted fever, 381– 398b cancer, 275
382, 382f, 382b–383b and bladder cancer, 958 Sepsis, 72–73, 102
Rodent ulcers, 1148b Schistosomiasis, 397, 397b–398b, 862 perinatal, 462
ROM, Rupture of membranes and parasitic enterocolitis, 797 Septic shock, 102
ROS, Reactive oxygen species Schlemm canal, 1306f pathogenesis of, 135–137
Rosacea, 1165, 1165b Schneiderian papilloma, 741, 741f pathogenic pathways in, 136f
Rosenthal fibers, 1243 Schwann cells, 1218 severity and outcome of, 137
Rotavirus, and viral gastroenteritis, 795 Schwannomas, 1237, 1238f Septicemic plague, 367b
Rotor syndrome, 853t morphology of, 1237b Sequence, 455, 455f
Rough endoplasmic reticulum (RER), 6– Schwannomatosis, 1302 Sequestration
7, 13 SCID, Severe combined immunodeficiency crises, in sickle cell disease, 644
Rouleaux formation, 608b–609b Scirrhous tumors, 268 pulmonary, 674
RPE, Retinal pigment epithelium Sclera, 1306f, 1310 Sequestrum, 1186b
RPGN, Rapidly progressive Scleroderma, 231–234, 690–691 SER, Smooth endoplasmic reticulum
glomerulonephritis Sclerosing adenosis, of breast, 1043f, 1043b Serine protease inhibitor Kazal type 1
RTKs, Receptor tyrosine kinases Sclerosing lymphocytic lobulitis, 1041 (SPINK1) gene, pancreatitis, 884, 884t
Rubor, 73, 95–96 Sclerosing retroperitoneal fibrosis, of Seronegative spondyloarthropathies, 1202–
RUNX2, 1173 ureters, 954 1203
Rupture of membranes (ROM), preterm SCN4A, mutations of, 1236 Serositis, in systemic lupus
premature, 458 Scrub typhus, 381, 382b–383b erythematosus, 222t
Serotonin, in inflammation, 86 Sickle cell anemia, genetic basis for, 144 in basal cell carcinoma, 1147–1148
Serous borderline tumors, 1019f, 1019b Sickle cell crisis, in liver, 862f melanoma as, 1139–1142
Serous carcinoma Sickle cell disease, 641–644, 650b Skin disorders, 1154
endometrial, 1011–1012, 1012b clinical features of, 643–644 adnexal (appendage) tumors, 1144–1145
ovarian, 1009f, 1013b diagnosis of, 644 benign epithelial tumors, 1142–1143
Serous cystic neoplasms, of pancreas, 888– morphology of, 642b, 643f acanthosis nigricans, 1143
889, 889f, 890b pathogenesis of, 641–642, 642f fibroepithelial polyp, 1143
Serous tumors, of ovaries, 1018– Sickle-cell nephropathy, 940 seborrheic keratosis, 1142
1020, 1019f–1020f, 1019b Sickle cell trait, 144, 641 blistering (bullous), 1159–1164
Sertoli cell tumors, testicular, 974 Sickle hemoglobin (HbS), 641 inflammatory, 1159–1164
Sertoli-Leydig cell tumors, of Sickle retinopathy, 1322–1323 noninflammatory, 1163–1164
ovaries, 1027–1028, 1027f, 1027b– SIDS, Sudden infant death syndrome due to infections
1028b Sievert (Sv), as radiation unit, 429 impetigo, 1168
Serum amyloid A (SAA) protein, 102 Sigmoid septum, 529 superficial fungal, 1169
Serum sickness, 211t Signal transduction pathways, 17–19, 18f of epidermal appendages, 1165
acute, 211 modular signaling proteins, hubs, and nodes acne vulgaris, 1165
Sever acute malnutrition (SAM), 433–435 in, 19 rosacea, 1165
Severe combined immunodeficiency transcription factors in, 19–20 of epidermal maturation, 1152–1153
(SCID), 242–243 Signaling lymphocytic activation molecule ichthyosis, 1152–1153
Sex chromosomes, cytogenetic disorders family member 1 (SLAMF1), in familial cancer syndromes with cutaneous
involving, 170–173, 173b measles, 350 manifestations, 1148t
Sex cord-gonadal stroma, tumors of, 974 Silica, lung diseases due to, 692t infection, 1166–1169
Sex cord-stromal tumors, of Silicosis, 691, 693, 693f–694f, 693b–694b molluscum contagiosum, 1168
ovaries, 1017t, 1026–1028, 1028b chronic inflammation in, 96 verrucae (warts), 1167
Sex steroids, 1114–1115 SILs, Squamous intraepithelial lesions inflammatory dermatoses as
Sexually transmitted infections (STIs), 399– Simple karyotype, 1208 acute, 1153–1156
400 Simple (capillary) lymphangiomas, 520 chronic, 1157–1158
classification of, 400t Simplified Diagnostic Criteria (2008) of the panniculitis, 1166
Sézary syndrome, 595t, 606, 1151 International Autoimmune Hepatitis of pigmentation and melanocytes, 1135–1142
SFTBC gene, 459 Group, 840t dysplastic nevi, 1137–1138
SFTPB gene, 459 Single-base primer extension, 181–182 freckles (ephelis), 1135
Shadow plaques, in multiple Single-gene disorder(s), 492 lentigo, 1136
sclerosis, 1270b–1271b Mendelian, 144–163 melanocytic (pigmented) nevus (mole), 1136–1137
Shaw, George Bernard, 73 with nonclassic inheritance, 173–180 melanoma, 1139–1142
Sheehan syndrome, 1073 Single nucleotide polymorphism (SNP) premalignant and malignant epidermal
Shingles, 355b, 1266 genotyping arrays, 183, 183f tumors, 1145–1148
Shock, 115–139, 138b Sinoatrial (SA) node pacemaker, 528 actinic keratosis, 1145–1146
anaphylactic, 135 Sinonasal papilloma, 741, 741f basal cell carcinoma, 1147–1148
cardiogenic, 134 Sinus histiocytosis, 589b squamous cell carcinoma, 1146–1147
clinical features of, 138 Sinus venosus defects, 537b tumors of cellular migrants to, 1151–1152
hemorrhagic, 125 Sinusitis, 739–740 mastocytosis, 1152
hypovolemic, 134 Sinusoidal obstruction syndrome, 863, 863f mycosis fungoides, 1151
lung, 138b morphology of, 863b tumors of dermis, 1149–1151
morphology of, 138b Sipple syndrome, 1130 dermatofibrosarcoma protuberans, 1150–1151
neurogenic, 135 siRNAs, Small interfering RNAs fibrous histiocytoma, 1149
stages of, 137–138 SIRS, Systemic inflammatory response Skin lesions
with systemic inflammation, 134–135 syndrome nomenclature of, 1135t
types of, 135t Sirtuins, and cellular aging, 68 in sarcoidosis, 696b–697b
Short stature homeobox (SHOX) gene, 171 Sjögren syndrome, 229–231, 230f, 231b Skin wounds, healing of, 108–110
“Shower embolization,”, 1253–1254 autoantibodies in, 222t Skull fractures, 1249
Shunt, 536 clinical features of, 230–231 displaced, 1249
left-to-right, 536–538, 538f etiology and pathogenesis of, 230 SLAM-associated protein (SAP), 245
due to atrial septal defect, 536–537, 538f morphology of, 230b SLL, Small lymphocytic lymphoma
due to patent ductus arteriosus, 538, 538f Skeletal muscle SMA, Spinal muscular atrophy
due to patent foramen ovale, 537 atrophy, 1227 Small-airway disease, 678t
due to ventricular septal defect, 537–538, 538f–539f congenital myopathies of, 1231t Small-caliber minor papilla, 881
right-to-left, 538–540, 539f diseases of, 1227–1236, 1236b Small cell carcinoma, 717, 721
due to persistent truncus arteriosus, 538 fiber types, 1227t of bladder, 962
due to tetralogy of Fallot, 538–539, 539f inherited diseases of, 1231–1236 of lung, 1115
due to total anomalous pulmonary venous neurogenic/myopathic changes in, 1227– Small cell change, in liver, 869f, 869b–870b
connection, 538 1228, 1227f Small interfering RNAs (siRNAs), 4–5
due to transposition of the great arteries, 539– Skeletal muscle tumors, 1211–1212 Small intestine
540, 539f–540f Skeletal syphilis, 1186–1187 ischemic bowel disease of, 781–783, 781b–
due to tricuspid atresia, 538 Skeletal system, in hyperthyroidism, 1076 782b, 782f
SIADH, Syndrome of inappropriate Skin, 1133–1170, 1134f obstruction of, 780–781, 780f
antidiuretic hormone infections via, 340, 340t Small lymphocytic lymphoma
Sialolithiasis, 747–748 as mechanical barrier, 1133–1135 (SLL), 595t, 597–599, 598f, 604b–605b
Sicca syndrome, in Sjögren syndrome, 229 in systemic lupus erythematosus, 225b–228b morphology of, 597b
Sick building syndrome, in indoor air in systemic sclerosis, 232b Smegma, 963–964
pollution, 410 Skin cancers
SMO protein, in nevoid basal cell Spinal cord injury, 1252 Staphylococcus aureus, in pyogenic
carcinomas, 1148 Spinal dysraphism, 1246 osteomyelitis, 1185–1186
Smog, 408–409 Spinal muscular atrophy (SMA), 1235– Staphyloma, 1310, 1326b
Smoke inhalation, passive, 417–418 1236, 1236f, 1289 Stasis
Smokeless tobacco, 415 Spindle and epithelioid cell nevus, 1136t in inflammation, 75–76
health effects of, 418b Spinocerebellar ataxias (SCAs), 1286–1287 and thrombosis, 125–126
Smoking, 415 Spinocerebellar degenerations, 1286–1287 Statins, 495–496, 1230
and lung cancer, 416, 416t, 417f Spirochetes, 375–379 Status asthmaticus, 683, 686b
and other diseases, 416–418, 417f Spironolactone bodies, 1119b Status marmoratus, 1248
white cell neoplasia and, 592 Spitz nevus, 1136t Steatosis, 62, 63f
“Smoky coal,”, 693 Spleen, 628–631, 629f Stem cells, 28
Smoldering myeloma, 607, 610, 611b amyloidosis of, 263b–264b cancer, 282, 304
Smooth endoplasmic reticulum (SER), 6– congenital anomalies of, 631 niches, 28, 29f
7, 13 in immune system, 197 in tissue regeneration, 103
Smooth muscle cells, vascular, in response in infectious mononucleosis, 358b Stereotyped response to vascular
to injury, 488 morphology of, 629b–630b injury, 488–489, 489f
Smooth muscle proliferation, in neoplasms in, 630–631 Steroids
atherosclerosis, 498 rupture of, 631 hormones, obesity in, 449
Smooth muscle tumors, 1213 in sarcoidosis, 696b–697b tissue repair and, 108
Soap-bubble lesion, 386f in sickle cell disease, 643–644, 643f Stevens-Johnson syndrome, 1156b–1157b
Sodium retention, edema due to, 116 in systemic lupus erythematosus, 225b–228b STIs, Sexually transmitted infections
Soft chancre, 367, 367b Splenic infarcts, 630, 631f STK11 gene, 299
Soft tissue, 1208–1214 morphology of, 630b Stomach, 764–779, 779b–780b
pathogenesis of, 1208–1209 in sickle cell disease, 643f, 644 dysplasia of, 771
tumors, 1210t, 1214b Splenic rupture, 631 gastritis of, 765–766, 765f, 766b, 773b
in adipose tissue, 1209 Splenic white pulp, 197 autoimmune, 768–769, 768t, 769f, 769b
chromosomal abnormalities in, 1209t Spleniculi, Accessory spleens cystica, 771
fibrous, 1211 eosinophilic, 769
in skeletal muscle, 1211–1212 granulomatous, 769–770
in smooth muscle, 1213 Splenomegaly, 629–630 Helicobacter pylori, 767–768, 767b, 768f, 768t
of uncertain origin, 1213–1214 congestive, 630 lymphocytic, 769
Soft tissue callus/procallus, 1184 disorders associated with, 630t uncommon forms of, 769–770
Soft tissue tumors, 1171–1215 Spongiform, in prion diseases, 1275b, 1276f hypertrophic gastropathies of, 771–773, 772t
Solid-pseudopapillary neoplasm, of Spongiosis, 1135t, 1155b Ménétrier disease of, 771–772, 772f, 772b
pancreas, 890 Spontaneous idiopathic pneumothorax, 726 mucosal atrophy and intestinal metaplasia
Solitary myeloma, 607, 610, 611b Sporadic goiter, 1083 of, 771
Solitary nodules, in thyroid, 1085 Spot desmosomes, 12 peptic ulcer disease of, 770–771, 770f, 770b–
Solitary tumors, 1113b Squamocolumnar junction, of 771b
Somatic hypermutation, 591 cervix, 995, 995f polyps of, 773–779
Somatic motor function, 1217 Squamous cell carcinoma fundic gland, 773, 773b–774b
Somatic sensory function, 1217 (SCC), 269, 271f, 716, 720f inflammatory and hyperplastic, 773, 773b, 774f
Somatostatin, 1097 of bladder, 962 stress-related mucosal disease of, 766, 766b
Somatostatinomas, 1114 of cervix, 999f, 999b–1000b tumors of, 773–779
Somatotroph, 1068t of esophagus, 763–764, 763f adenocarcinoma, 774–776, 775f–776f, 775b–776b
Somatotroph adenomas, 1071, 1071b head and neck, 735–736, 736b–737b adenoma, 774, 774b
Sommer sector, 1256 of oral cavity, 735–736, 736b–737b, 737f–738f carcinoid, 777b, 778f
Sonic hedgehog (SHH) gene, in basal cell of penis, 964–965, 965f, 965b–966b, 966t gastrointestinal stromal tumor, 778–779, 779f, 779b
carcinoma, 1148, 1149f of skin, 1146–1147, 1147f, 1147b–1149b lymphoma, 776–777, 777f, 777b
Soot of vagina, 994 Zollinger-Ellison syndrome of, 773
as air pollutant, 409 Squamous cell hyperplasia, of Stop codon, 142
occupational health risks, 415 vulva, 990, 990f Storage pool disorders, 667
Southern blotting, 180, 182f Squamous epithelial cells, 1133 “Strawberry cervix,”, 988
SOX9, 1173 Squamous intraepithelial lesions Streak ovaries, 173
Sparsely granulated lactotroph (SILs), 997–998, 997b, 999t Streptococcal infections, 360–361, 361b
adenomas, 1070b Squamous metaplasia Streptococcal pharyngitis, 361b
Spatial separation, 185 of bladder, 957 Stress
Specialized teratomas, 1024 due to vitamin A deficiency, 437 endoplasmic reticulum, 54, 55f
Spectrin, in hereditary of lactiferous ducts, 1040–1041, 1040f oxidative, cell injury due to, 52t, 53f
spherocytosis, 638, 638f Squamous neoplastic lesions, of vulva, 991– Striated muscle cells, 1101, 1101f
Spermatic cord, tumors of, 969 993 Stromal hyperthecosis, 1016
Spermatocele, 974 Squamous papilloma(s) Stromal nodule, of endometrium, 1015b
Spermatocytic seminoma, 970–971, 971b laryngeal, 743f Stromal tumors
Spherocytosis, hereditary, 638–640, 638f– of vulva, 990–991 of breast, 1061–1063
639f Stable tissues, 103–104 of endometrium, 1013–1014, 1015b
Sphingomyelin, 9 Staging, of cancer, 330 Strongyloides, and parasitic
“Spider cells,” in cardiac Staphylococcal infections, 359– enterocolitis, 796
rhabdomyomas, 580b 360, 359f, 360b, 361f Strongyloides stercoralis, 395, 395f
Spider telangiectasias, 519 breast and, 1040 Strongyloidiasis, 395, 395b
Spina bifida, 1246 Staphylococcal scalded-skin Structural proteins, defects in, 148–151
Spinal cord infarction, 1256f syndrome, 360b
Struma lymphomatosa, Hashimoto Symptomatic primary responses of differentiated effector T cells
thyroiditis, 1078 hyperparathyroidism, 1095–1096 in, 213–214
Stunned myocardium, 550 Synaptic signaling, 17 T cell-mediated reactions, in transplant
Sturge-Weber syndrome, 519, 1314 Synarthroses, 1197 rejection, 236
Subacute cerebellar degeneration, in Syndactyly, 454f, 1174 T-cell neoplasms, 594–597
paraneoplastic syndromes, 1301 Syndrome, 455–456 T-cell origin, tumors of, 607
Subacute cutaneous lupus Syndrome of inappropriate antidiuretic T-cell receptor (TCR) complex, 194f–195f
erythematosus, 229 hormone (SIADH), 1074 T-cell receptors (TCRs), 203b–204b
Subacute lymphocytic (painless) Synovial cysts, 1207 T lymphocytes, 194–195, 203b–204b
thyroiditis, 1080, 1080b Synovial fluid, 1197 activation of, 200–201
Subacute neuronal injury, 1242b Synovial sarcoma, 1213, 1213f, 1213b in chronic inflammation, 97
Subacute sensory neuropathy, in α-Synuclein, 1282 in glomerular injury, 904
paraneoplastic syndrome, 1302 Syphilis, 375–377, 376f, 377b–378b helper (TH), 194–195, 202f
Subaortic stenosis, 541 epididymitis and orchitis due to, 968 recirculation of, 197–198
Subarachnoid hemorrhage, 1073, 1258– manifestations of, 375f naive, 200
1260 primary, 376, 377f, 377b–378b recognition of graft alloantigens by, 234–235
Subareolar abscess, recurrent, 1040 secondary, 376, 377b–378b Tabes dorsalis, 1264b
Subcutaneous tissues, in right-sided heart serologic tests for, 377 Taenia solium, 395
failure, 533b tertiary, 376, 377b–378b, 378f Takayasu arteritis, 512, 512f, 512b
Subdural empyema, 1263 Syphilitic bone infection, 1187b Takotsubo cardiomyopathy, 517
Subdural hematoma, 1251– Syphilitic gummas, 377b–378b, 378f Tall-cell variant, 1088b–1089b
1252, 1251f, 1251b–1252b Syringobulbia, 1248 Tapeworms, 396b
Subendocardial (nontransmural) Syringoma, 1144 infection, 395–396
infarction, 547 Syringomyelia, 1248 Target lesions, in aspergillosis, 387b
Subependymomas, 1296b–1298b Syrinx, 1248 Targeted sequencing, 186
Subfalcine (cingulate) Systemic acute-phase response, in Tattooing, 64
herniation, 1245, 1245f inflammation, 89–90 tau, in Alzheimer disease, 1276–1277
Substance P, in inflammation, 92 Systemic connective tissue diseases, Tax gene, 324
Substantia nigra, pallor of, 1283b neuropathy associated with, 1221 Tay-Sachs disease, 156–157, 1323, 1323f
Substrate Systemic disease ganglion cells in, 157f
accumulation of, 147–148 diet and, 450 TBX1, in congenital heart disease, 535
catabolism of, 154 oral manifestations of, 733–734, 734t TBX5, in congenital heart disease, 535–536
tissue-damaging, 148 in skin, 1134–1135 TCGA, The Cancer Genome Atlas
Substrate reduction therapy, for lysosomal Systemic immune complex disease, 211– TCRs, T-cell receptors
storage diseases, 155 212 TDS, Testicular dysgenesis syndrome
Sudden cardiac death (SCD), 542, 555 Systemic inflammatory response syndrome Teeth, diseases of, 731
Sudden infant death syndrome (SIDS), 473– (SIRS), 135 Telangiectasia(s), 518–519, 1228
475, 474t, 474b Systemic lupus erythematosus, 211t, 221– hereditary hemorrhagic, 519, 663
Sulfur dioxide 229, 229b spider, 519
in air pollution, 409 autoantibodies in, 222t Telomerase, 67–68, 68f
lung diseases due to, 692t clinical and pathologic manifestations of, 226t in aplastic anemia, 659
Superantigens, 137, 347, 360 clinical features of, 228–229 in cancer, 303–304
Superficial cutaneous neurofibromas, 1237 criteria for classification of, 222t mutations that activate, 1140
Superficial fibromatosis, 1211 endocarditis of, 565 Telomere attrition, 67–68
Superficial fungal infections, 1169 etiology and pathogenesis of, 224–225 Telomeres, 67–68, 68f
Superinfection, in HDV, 835–836 HLA alleles and, 219t alternative lengthening of, 303–304
Superior vena cava syndrome, 517– model for pathogenesis of, 224–225, 225f progressive shortening of, 303–304, 304f
518, 580, 1084 morphology of, 225b–228b Tenascin-X, 150–151
Supernumerary digit, 1174 skin, 228f Tenosynovial giant cell tumor, 1207–
Superoxidase dismutase, 53 spectrum of autoantibodies in, 221–229 1208, 1207b, 1208f
Superoxide, in phagocytosis, 83 Systemic sclerosis, 231– Tension pneumothorax, 726
Superoxide anion, in inflammation, 82–83 234, 233f, 234b, 691 Teratoma, 269
Superoxide dismutase, 83 autoantibodies in, 222t cystic, 269f
Suppurative arthritis, 1203 clinical features of, 233–234 in infants and children, 476–477
Supravalvular aortic stenosis, 541 etiology of, 231–232 testicular, 972–973, 972b–973b, 973f
Surface epithelial tumors, of ovaries, 1022– morphology of, 232b Terminal bronchioles, 673–674
1023 pathogenesis of, 231–232, 231f Terminal digestion, 783
Surfactant, 459 Systolic dysfunction, 529 Testicular dysgenesis syndrome
exogenous, prophylactic administration of, 460 Systolic failure, 533 (TDS), 969–970
of lungs, 674 Testicular lymphoma, 974
protein B, 700 Testicular tumors, 969–974, 969t, 974b
protein C, 700 germ cell, 969–973, 969t
synthesis of, 459 T choriocarcinoma, 972, 972f, 972b
Surfactant deficiency, neonatal respiratory T-cell acute lymphoblastic classification of, 969t, 970
distress syndrome due to, 459 leukemia/lymphoma, 595t clinical features of, 973
Surgically induced T cell-mediated (type IV) embryonal carcinoma, 971, 971f–972f, 971b
hypoparathyroidism, 1096 hypersensitivity, 204t, 212–215 environmental factors of, 969–970
Sweat glands, 1134 diseases of, 213t genetic factors of, 970
Sympathetic ophthalmia, 1316, 1316f mechanisms of, 213f, 215b mixed, 973
nonseminomatous, 973
pathogenesis of, 969–970, 969f bleeding related to, 663–666 Thymic cysts, 632
seminoma, 970, 970f–971f, 970b causes of, 664t Thymic follicular hyperplasia, 632
spermatocytic, 970–971, 971b dilution, 664 Thymic hyperplasia, 632, 1226
teratoma, 972–973, 972b–973b, 973f drug-induced, 665 Thymic hypoplasia, 244, 631
yolk sac tumor, 971, 972b heparin-induced, 127, 665 Thymoma, 632–633, 632f, 1226
gonadoblastoma, 974 HIV-associated, 665 morphology of, 632b–633b
lymphoma, 974 immune, 663–664 Thymus, 631–633
of sex cord-gonadal stroma, 974 intracerebral hemorrhage and, 125 developmental disorders of, 631–632
spermatic cord and para-, 969 petechiae due to, 125f Thyroglossal duct cyst, 745, 1092
Testis, 966–974 in systemic lupus erythematosus, 222t Thyroid adenomas, 271f, 1085–
atrophy of, 967 Thrombocytopenic purpura 1086, 1085b–1086b
congenital anomalies of, 966–967, 967f immune Thyroid carcinomas, 1086–1092, 1088b–
cryptorchidism, 966–967, 966b–967b, 967f acute, 665 1089b
inflammation of, 967–968, 968f chronic, 664–665 Thyroid disorder(s)
regressive changes of, 967 thrombotic, 665–666, 666t, 671b goiter, 1082–1084
torsion of, 968, 968f, 968b Thromboembolic disease, 115–139 diffuse nontoxic (simple), 1083
tumors of, 969–974, 969t, 974b disseminated intravascular coagulation, 130 Graves disease, 1081–1082, 1082f
germ cell, 969–973 hemostasis, 118–130 hyperthyroidism, 1075–1077
gonadoblastoma, 974 infarction due to, 133–134 hypothyroidism, 1077–1078
lymphoma, 974 Thromboembolism, 130–131 cretinism, 1078
of sex cord-gonadal stroma, 974 oral contraceptives in, 422 myxedema, 1078
spermatic cord and paratesticular, 969 systemic, 131 thyroiditis, 1078–1081
tunica vaginalis of, 974 Thrombomodulin, 123–124, 669 Hashimoto, 1078–1080, 1079f
vascular disorders of, 968, 968f Thrombophilias, 127 subacute (granulomatous, De Quervain
Tetanus, 380 Thrombophlebitis, 517 thyroiditis), 1080–1081, 1080f
Tetany, hypocalcemia, 1097 migratory, 130 subacute lymphocytic (painless), 1080
Tetrahydrofolic acid (FH4), 653–654, 653f due to pancreatic carcinoma, 893 Thyroid dysfunction, 1223
Tetralogy of Fallot (TOF), 538–539, 539f Thromboplastin time, partial, 662 Thyroid follicular epithelial cells, 1075
TFPI, Tissue factor pathway inhibitor Thrombosis, 118–130, 130b Thyroid gland, 1075–1092
TGA, Transposition of the great arteries alternations in normal blood flow, 126 follicular cell-derived malignancies of, 1087f
TGF-α, Transforming growth factor-α antifibrinolytic effects of, 126 neoplasms of, 1084–1092
TGF-β, Transforming growth factor-β in antiphospholipid antibody syndrome, 127– Thyroid hormone (T3), 1173
Th1 response, in tuberculosis, 368 128 Thyroid myopathy, 1076
Th2 cells arterial, 130, 133 Thyroid neoplasms, 1092b
activation of, in immediate in atherosclerotic plaque, 504 Thyroid ophthalmopathy, 1306, 1307f
hypersensitivity, 205–206 cardiac, 130 Thyroid stimulating hormone (TSH), 1075
in asthma, 684 defined, 118 Thyroid stimulating immunoglobulin
Thalassemia(s), 644–648, 650b endothelial injury in, 126 (TSI), 1081
α, 646t, 647 fate of thrombus in, 129–130 Thyroid storm, 1076–1077
clinical syndromes of, 648 in heparin-induced thrombocytopenia Thyroiditis, 1078–1081, 1081b
β, 644 syndrome, 127 cretinism, 1078
clinical syndromes of, 646–647, 646t, 647f hypercoagulability in, 126–128, 126t Hashimoto, 1078–1080, 1079f
genetic basis for, 646t morphology of, 128b–129b subacute
intermedia, 646, 646t venous, 128b–129b, 130 granulomatous, De Quervain thyroiditis, 1080–
major, 646f, 646t, 647 Virchow triad in, 125, 125f 1081, 1080f
minor, 646t, 647 Thrombotic endocarditis, lymphocytic (painless), 1080
molecular pathogenesis, 644–646, 646f nonbacterial, 128b–129b Thyrotoxic myopathy, 1231
morphology of, 647b Thrombotic microangiopathies, 665– Thyrotoxicosis, 1075–1076
Thalassemia trait 666, 666t disorders associated with, 1076t
α, 646t, 648 renal disease due to, 937–939, 937f, 937t, 939b Thyrotroph(s), 1068t
β, 646, 646t Thrombotic occlusions, cerebral infarction Thyrotroph (TSH-producing)
Thalidomide, as teratogen, 456 due to, 1254 adenomas, 1072
Thanatophoric dysplasia, 1175, 1176t Thrombotic thrombocytopenic purpura Tight junctions, 12
The Cancer Genome Atlas (TCGA), 334 (TTP), 665–666, 666t Tin oxide, lung diseases due to, 692t
Therapeutic drugs, injury by, 420–423 renal disease in, 939, 939b Tinea
Thermal burns, 427, 427b Thromboxane A2 (TxA2) barbae, 1169
Thermal injury, 427–428 in inflammation, 88 capitis, 1169
Thermogenesis, leptin in, 446 in platelet aggregation, 120 corporis, 1169, 1169f
Thiamine (vitamin B1) deficiency, 420 Thrombus(i) cruris, 1169
CNS effects of, 1291 arterial, 128b–129b pedis, 1169
Thin basement membrane lesion, 922– clinical features of, 130 versicolor, 1169
923, 923b fate of, 129–130 Tingible-body macrophages, 589b
Thoracic aortic aneurysm, 507 formation of, 118 Tissue damage, in inflammation, 72
Thrombasthenia, Glanzmann, 120 morphology of, 128b–129b Tissue factor, in hemostasis, 118–119
Thrombin mural, 128f–129f, 128b–129b Tissue factor pathway inhibitor (TFPI), 123–
in coagulation cascade, 122, 669 red, 128b–129b 124
in hemostasis, 122f stasis, 128b–129b Tissue injury, type and extent of, tissue
in inflammation, 122 Thrush, 384b–385b, 733 repair and, 108
Thromboangiitis obliterans, 515, 515f, 515b Thymic aplasia, 631 Tissue necrosis, 348–349
Thrombocytopenia, 431–432 Thymic carcinoma, 632b–633b inflammation due to, 74
Tissue plasminogen activator (t-PA), 119 Transcription factors, oncogenes for, 289– Tropism, of viruses, 345
Tissue regeneration, 103–105 290 Troponins, in myocardial infarction, 550
mechanisms of, 104 Transcytosis, 11 Trousseau sign
Tissue repair, 103–111 Transection, neuroblastoma, 478b due to pancreatic carcinoma, 893
abnormalities in, 110–111 Transepithelial transport, and hypoparathyroidism, 1097
factors that influence, 108 malabsorption, 783 Trousseau syndrome, 130
and fibrosis, clinical examples of, 108–110 Transferrin, 83, 655 Truncus arteriosus, persistent, 538
mechanisms of, 103f “Transformation zone,” of cervix, 995 Trypanosoma cruzi, 393
overview of, 103 Transforming growth factor-α (TGF- Trypsin, in pancreatitis, 882–883
Tissue stem cells, 28 α), 20, 20t Trypsinogen gene, 884
Tissue transplants, rejection of, 234–240 Transforming growth factor-β (TGF- TSH, Thyroid stimulating hormone
TLRs, Toll-like receptors β), 20t, 107 TSI, Thyroid stimulating immunoglobulin
TNF, Tumor necrosis factor in Marfan syndrome, 149 TTP, Thrombotic thrombocytopenic purpura
TNM staging system, 330 pathway, tumor suppressor genes in, 298 Tubal pregnancy, 1029–1030, 1029b
Tobacco, effects of, 415– Transfusion, complications of Tubercle, 101
418, 416f, 416t, 418b allergic reactions, 671 Tuberculin reaction, 214
Tobacco smoke, as indoor air pollutant, 410 hemolytic reactions, 671–672 Tuberculomas, 1263b
Tobacco smoking, carcinoma and, 716 infectious, 672 Tuberculosis, 368–371, 369f
TOF, Tetralogy of Fallot transfusion-related acute lung injury, 672 of brain, 1263–1264, 1263b
Tolerance-breaking drugs, Transfusion-related acute lung injury clinical features of, 369–371, 370f
immunohemolytic anemia due to, 649 (TRALI), 672 epidemiology of, 368
Toll-like receptors (TLRs), 74, 442 Transitional cell tumors, of epididymitis and orchitis due to, 968
defects in, 241 ovaries, 1022, 1022b granulomatous inflammation and, 101
engagement by nuclear DNA and RNA, 224 Translocations, chromosomal, in intestinal, 371b–373b
in innate immunity, 191 cancer, 316–317, 316t isolated, 371b–373b
in septic shock, 135–136 Transmembrane receptor RANK, 1173– lymphadenitis in, 371b–373b
Tonsillar herniation, 1245, 1245f 1174 miliary pulmonary disease, 371b–373b
Tonsillitis, 740 Transmigration, of leukocytes through morphology of, 371b–373b, 372f
Tooth decay, 731 endothelium, 78–79 pathogenesis of, 368–369
Tophi, 1205b Transmural infarction, myocardial, 546–547 primary, 369–370, 371b–373b
TORCH infections, perinatal, 462 Transplacental (hematologic) progressive, 371b–373b
Torsion, testicular, 968, 968f, 968b infections, 461–462, 462f secondary, 370, 371b–373b, 372f
Total anomalous pulmonary venous Transplant-associated KS, 521 systemic miliary, 371b–373b, 373f
connection, 538 Transport systems, defects in, 148 Tuberculous adrenalitis, 1123
Total-body irradiation, effects of, 431, 431t Transporters, 1176–1178 Tuberculous cystitis, 955
Toxemia of pregnancy, 458 Transposition of the great arteries Tuberculous granuloma, 100f
Toxic agents, chronic inflammation due (TGA), 539–540, 539f–540f Tuberculous salpingitis, 1015
to, 96 Transtentorial herniation, 1245, 1245f Tuberous sclerosis, 1148t
Toxic disorders, CNS effects of, 1292–1293 Transthyretin (TTR), in amyloidosis, 260 Tuberous sclerosis complex, 1302, 1302b
Toxic epidermal necrolysis, 1156b–1157b Transudate(s), 75, 115–116 Tubo-ovarian abscesses, 989b
Toxic granules, 588, 588f formation of, 75f Tubular carcinoma, of breast, 1056b–
Toxic metabolites, 407–408 Trauma 1058b, 1059f
Toxic multinodular goiter, 1084 central nervous system, 1249–1252 Tubulointerstitial fibrosis, 906
Toxic myopathies, 1230–1231 concussion, 1249 Tubulointerstitial nephritis, 926–927, 926t
Toxic neuropathies, 1223 diffuse axonal injury, 1250 acute vs. chronic, 927
Toxic shock syndrome, 347 parenchymal injuries, 1249–1250 drugs and toxins induced, 931–933, 932b–933b
Toxicology, 407 sequelae of, 1252 due to bile cast nephropathy, 935
Toxins, disorders caused by, 1226 skull fractures, 1249 due to hypercalcemia and nephrocalcinosis, 933
Toxin-induced liver injury, 841–842, 842b spinal cord, 1252 due to light-chain cast
patterns of injury in, 841t vascular injury, 1250–1252, 1251t nephropathy, 934, 934f, 934t, 934b
Toxoplasma gondii, 256 inflammation due to, 74 due to urate nephropathy, 933, 933f
Toxoplasmosis, 394, 394f, 394b, 1269b, 127 Traumatic neuroma, 1218 Tubulointerstitial pattern, of acute T cell-
0f Treponema pallidum, 375f mediated rejection, 236b
TP53, 294–297, 297b Trichinella spiralis, 396, 396b–397b, 397f Tumor(s), 268
in apoptosis, 295–296 Trichinosis, 396, 396b–397b of adipose tissue, 1209
and breast cancer, 1047, 1049t Trichoepithelioma, 1144f, 1144b–1145b anaplastic, 271f
in DNA damage and hypoxia, 295 Trichomonas vaginalis, 988 basic components of, 268
loss of function, 296–297, 303 Trichuris trichiura, and parasitic benign epithelial, 1142–1143
in osteosarcoma, 1188 enterocolitis, 796 bone-forming, 1187–1189
in senescence, 295 Tricuspid atresia, 538, 540 cartilage-forming, 1189–1192
transient, 295, 296f Trinucleotide-repeat mutations, disease characteristics of benign and malignant, 270–
Trabecular meshwork, 1306f caused by, 173–177, 174t, 175f 276, 276t, 276b–277b
Trace elements, deficiency syndromes, 444t Triphenyltetrazolium chloride, in differentiation and anaplasia, 270–273, 271f, 276t
TRALI, Transfusion-related acute lung myocardial infarction, 547b–549b, 548f local invasion, 273, 276t
injury Trisomy 13, 168f, 169 metastasis, 273–276
Transcervical (ascending) infections, Trisomy 18, 168f, 169 clinical aspects of, 331b
perinatal, 461 Trisomy 21, 166–169, 167f–168f of dermis, 1149–1151
Transcobalamin II, 652–653, 652f Triton tumor, 1238b–1239b evolution of, 283f
Transcription factors, 19–20 Trophozoite, of malaria, 389 grading and staging of, 330
Tropical sprue, 783t, 786 host defense, evasion of
antitumor effector mechanisms in, 311, 311f of nasopharynx, 740, 742b staging of, 959b–960b, 961t
immune surveillance and escape as, 309–313, 313b necrotizing lesions, 740 grading of, 959b–960b, 961t
mechanisms of, 311–313, 313f of nose, 739–740 morphology of, 957f, 959f–960f, 959b–960b
tumor antigens in, 309–310, 310f tumors of nose, sinuses, and nasopharynx, 740– noninvasive
in inflammation, 73, 95–96 743 flat, 957–958, 957f
local and hormonal effects of, 328 Up-regulation, of cyclin D1, 602 papillary, 957–958, 957f
molecular profiles of, 334–335 UPS, Undifferentiated pleomorphic sarcoma pagetoid spread, 959b–960b
progression, 283 Urachal cysts, 955 papillary
types, 335f Urachus, 955 carcinoma, 957f
of unknown origin, 1192–1195 Urate nephropathy, 933, 933f of low malignant potential, 959b–960b
Tumor antigens, 309–310, 310f Ureaplasma urealyticum, 988 noninvasive, 957–958
Tumor cells, circulating, 333 Uremia, 896, 897t papilloma, 959f, 959b–960b
Tumor giant cells, 271 Uremic neuropathy, 1223 Urothelium, 953
Tumor-like lesions, 475– Ureter(s), 954 Urticaria, 1153–1154, 1154f, 1154b
483, 954, 963, 1187–1196, 1197b, 1207– anatomy of, 953 pigmentosa, 1152, 1152b
1208 congenital anomalies of, 954, 954t Urticarial allergic reactions, 671
Tumor necrosis factor (TNF) disorders of, 955b Urushiol, 214
in cachexia, 328 hydro-, 954 USP6, 1194
in disseminated intravascular coagulation, 669 obstructive lesions of, 954, 954t Uterine leiomyoma, 1014
in inflammation, 88–90 sclerosing retroperitoneal fibrosis of, 954 Uteroplacental insufficiency, 458
Tumor suppressive miRs, 320 tumors and tumor-like lesions of, 954 Uterus
Tumor suppressor genes, 291– Ureteral obstruction, 954, 954t body of, 1001–1016
299, 292t, 299b Urethra, 963 leiomyoma of, 270f
in APC/β-catenin signaling pathway, 297 anatomy of, 953 physiologic hypertrophy of, 57, 58f
PTEN as, 298–299 carcinoma of, 963, 963f Uveitis, 1316
RB as, 293–294, 294f, 294b inflammation of, 963
silencing of, by local hypermethylation of tumor and tumor-like lesions of, 963, 963f
DNA, 319 Urethral caruncle, 963
in TGF-β pathway, 298 Urethritis, 963 V
TP53 as, 294–297, 296f, 297b gonococcal, 963 Vacuolization, 1135t
VHL as, 299 nongonococcal, 963 Vagina, 994–995
Tunica vaginalis, lesions of, 974 Uric acid, metabolism of, 1204 developmental anomalies of, 994
Turban tumor, 1144 Uric acid stones, 947, 947t embryonal rhabdomyosarcoma, 995, 995f
Turbulent blood flow, 125 Urinary bladder, 955–962 premalignant and malignant neoplasms of, 994–
Turner syndrome, 171–173, 172f anatomy of, 953 995
Turnover, collagen, 503–504 congenital anomalies of, 955, 955f squamous cell carcinoma of, 994
Twin placentas, 1030–1031, 1030f inflammation of, 955–957, 956f Vaginal adenosis, 994
Twin-to-twin transfusion syndrome, 1031 metaplastic lesions of, 957 Vaginal intraepithelial neoplasia, 994
“Two-hit” hypothesis, of oncogenesis, 291 neoplasms of, 957–962, 957t Vaginosis, bacterial, 988
Type I pneumocytes, 674 mesenchymal tumors, 962 Valvular heart disease, 557–567, 567b
Type II pneumocytes, 674 secondary, 962 aortic stenosis, 541
Typhus fever, 382f, 382b–383b urothelial tumors, 957–962, 958f–959f, 959b– Variable expressivity, 144–145
Tzanck test, 733b 960b, 961t Variant annotation, 185
obstruction of, 962 Variant calling, 185
morphology of, 962b Variant Creutzfeldt-Jakob
Urinary tract infection, 897, 927–931, 927f disease, 1275, 1275b
U Urinary tract obstruction, 927, 945– Variant interpretation, 185
UBE3A gene, 179 947, 946f, 946b Variant surface glycoprotein (VSG), in
Ubiquitin, 15 Urinary tract stones, in African trypanosomiasis, 392
Ubiquitin-proteasome pathway, in hyperparathyroidism, 1094b–1095b Varicella-zoster virus (VZV), 355, 355f
atrophy, 60 Urogenital sinus, 986, 986f encephalitis due to, 1266
Ulcer(s), 94, 94f Urogenital tract, infections via, 340t, 341 peripheral neuropathy in, 1222
Hunner, 956 Urolithiasis, 947–948, 947t, 948b Varicocele, 974
peptic, in Zollinger-Ellison syndrome Urothelial carcinoma, 954 Varicose veins, 517
(gastrinomas), 1114 Urothelial tumors, 957–962 Vasa vasorum, 486, 505
Ulceration, 1135t carcinoma Vascular amyloidosis, 264
Ulegyria, 1248 adeno-, 962 Vascular anomalies, in blood vessels, 487
Ultramutated/POLE tumors, 1008 clinical features of, 961–962 Vascular congestion, in inflammation, 75–
Ultraviolet (UV) light, in systemic lupus epidemiology of, 958 76
erythematosus, 224 high-grade, 959f, 959b–960b Vascular dementia, 1260
Ultraviolet rays, in cancer, 323 invasive, 959b–960b, 960f Vascular diseases
Unconjugated hyperbilirubinemia, 853t low-grade, 959f, 959b–960b atherosclerosis in, 493–494
Uncontrolled proliferation, 20 mixed, 962 hypertensive, 489–492
Undernutrition, 434 papillary, 958f, 959b–960b renal, 935–940
Undifferentiated pleomorphic sarcoma of low malignant potential, 959b–960b diffuse cortical necrosis, 939f, 939b
(UPS), 1214, 1214f, 1214b pathogenesis of, 958 renal artery stenosis, 936–937, 936b–937b
Unfolded protein response, 13, 54, 55f, 157 precursor lesions to, 957–958 renal infarcts, 940, 940b
Uniparental disomy, 179 in situ, 957–958, 958f, 959b–960b of testis and epididymis, 968, 968f
Upper airways, disorders of, 739–744 small-cell, 962 Vascular dissemination, in invasion and
of larynx, 743–744, 743f–744f squamous cell, 962 metastasis, 308–309
Vascular ectasias, 518–519 superior and inferior vena cava syndromes Vision, maintenance of normal, vitamin A
Vascular endothelial growth factor of, 517–518 in, 436–437
(VEGF), 20t, 21 thrombophlebitis and phlebothrombosis, 517 Visual impairment, due to diabetes
Vascular flow and caliber, in varicose, 517 mellitus, 1112
inflammation, 75–76 Velocardiofacial syndrome, 169 Vitamin A, 436–438
Vascular injury, of central nervous Venous leg ulcers, 110, 111f deficiency of, 437–438, 438f
system, 1250–1252, 1251t Venous thrombosis, 128b–129b, 130 forms of, 436–437
Vascular intervention, pathology of, 523– Ventricular aneurysm, due to myocardial functions of, 436–437
524, 524f infarction, 552 metabolism of, 437f
Vascular leakage, in inflammation, 76, 76f Ventricular assist devices, 581 sources of, 436
Vascular malformations, of brain, 1260 Ventricular remodeling, 553 toxicity of, 438
Vascular pattern, of acute T cell-mediated Ventricular septal defect (VSD), 537– Vitamin B1 deficiency, 420, 1223
rejection, 236b 538, 538f–539f, 538b CNS effects of, 1291
Vascular permeability, in in tetralogy of Fallot, 538–539, 539f Vitamin B6 (pyridoxine), deficiency
inflammation, 76, 76f in transposition of the great arteries, 539– of, 1223
Vascular reactions, in acute 540, 540f Vitamin B12
inflammation, 75 Verruca vulgaris, 1167f functions of, 653, 653f
Vascular replacement, 523–524, 524f Verrucous carcinoma, of penis, 965b–966b metabolism of, 652–653, 652f
Vascular tumors, 518–522, 522b Vertical transmission, 341 Vitamin B12 deficiency, 1223, 1291–1292
benign, 518–520 during birth, 341 Vitamin B12 deficiency anemia, 651t, 652–
bacillary angiomatosis, 520 placental-fetal, 341 653, 652f–653f
classification of, 518t postnatal, 341 Vitamin C, 442–443
glomus tumor (glomangioma), 520 Very-long-chain fatty acids (VLCFAs), in deficiency states of, 442–443, 442f
hemangioma, 519–520 adrenoleukodystrophy, 1290 function of, 442
lymphangiomas, 520 Very-low-density lipoproteins Vitamin D, 438–442
intermediate-grade (borderline) tumors, 520– (VLDLs), 151–152 on calcium and phosphorus homeostasis, effects
522 Vesicle, 1135t of, 440
hemangioendothelioma, 522 Vesicoureteral reflux, 927–928, 928f, 955 deficiency states of, 440, 440b–442b, 441f
malignant tumors, 522 Vesicouterine fistulae, congenital, 955 functions of, 440
angiosarcoma, 522 Vessel wall abnormalities, bleeding metabolism of, 438–440, 439f
Vascular wall, response to injury of, 489b disorders caused by, 663 nonskeletal effects of, 442
Vasculature, regional specializations VHF, Viral hemorrhagic fever toxicity of, 442
of, 486f Vibrio cholerae, 787 Vitamin D3, 438–439
Vasculitis, 508–516, 510f, 516b VIN, Vulvar intraepithelial neoplasia Vitamin deficiencies, 436–443, 443t
ANCA-associated small vessel, 514f Vinyl chloride primary malnutrition, 433
Buerger disease, 515 as carcinogen, 280t secondary malnutrition, 433
caused by ANCA, 210t occupational health risks, 415 of vitamin A, 437–438
Churg-Strauss syndrome, 515 VIPoma, 1114 of vitamin C, 442–443
immune complex-associated, 509–510 Viral arthritis, 1203 of vitamin D, 439f, 440
Kawasaki disease, 513 Viral hemorrhagic fever (VHF), 352, 352b Vitamin E, deficiency of, 1223
microscopic polyangiitis, 513–514 Viral hepatitis, 831–837, 838b VLCFAs, Very-long-chain fatty acids
neuropathy associated with, 1221–1222 acute asymptomatic infection with recovery VLDLs, Very-low-density lipoproteins
noninfectious, 509–516 in, 837 Vocal cords, 674
noninfectious disorders associated, 515–516 acute symptomatic infection with recovery Volume-overload hypertrophy, 530
polyarteritis nodosa, 513 in, 837 von Hippel-Lindau disease, 1302–1303
primary forms of, 509t clinicopathologic syndromes of, 836–837 von Hippel-Lindau (VHL) gene, 299
Vasculogenic mimicry, 1317b morphology of, 837b–838b von Hippel-Lindau (VHL) syndrome, 1127t
Vasoactive amines Viral infections, 349–358 in renal cell carcinoma, 949
in immediate hypersensitivity, 207 acute, 349–353 von Meyenburg complexes, 860, 860f
in inflammation, 86 chronic von Recklinghausen disease of
Vasoconstriction, 486, 504 latent (herpesvirus), 353–357, 354b–355b bone, 1094b–1095b, 1181b
due to shock, 137 productive, 357 von Willebrand disease, 668, 671b
in hemostasis, 118, 119f Epstein-Barr virus, 357–358 von Willebrand factor
influences, 492 herpes simplex viruses, 354 (vWF), 118, 120f, 667f, 668
Vasodilation, 486 measles, 350, 350f, 350b VSD, Ventricular septal defect
due to shock, 137 mumps, 350–351, 351b VSG, Variant surface glycoprotein
in inflammation, 75 poliovirus, 351 Vulnerable plaques, 503, 503f
Vasogenic edema, 1244 transforming, 357–358 Vulva, 989–993, 993b
Vaso-occlusive crises, in sickle cell West Nile virus, 351, 352b benign exophytic lesions of, 990–991
disease, 643–644 Viral injury, mechanisms of, 345, 345f condyloma acuminatum, 991, 991f
Vasopressin, 1067 Viral meningitis, 1262 extramammary Paget disease, 993, 993b, 994f
Vasospasm, coronary artery occlusion due Viral meningoencephalitis, 1264–1268 glandular neoplastic lesions, 993
to, 544 Virchow, Rudolf, 73, 1133 lichen sclerosus, 990, 990f
Vector-borne infectious diseases, climate Virchow triad, 125, 125f non-neoplastic epithelial disorders of, 990
change and, 406 Virus(es) papillary hidradenoma, 993, 993f
Vegetative endocarditis, 562f sexually transmitted infections, 400t squamous cell hyperplasia, 990, 990f
VEGF, Vascular endothelial growth factor tropism, 345 squamous neoplastic lesions, 991–993
Veins Visceral epithelial cells, 898, 899f, 901b vulvar carcinoma, 991–993
and lymphatics, 517–518 Visceral leishmaniasis, 392b vulvar intraepithelial neoplasia, 991–
993, 992f, 992b
Vulvar carcinoma, 991–993 and pathologic aspects of repair, 111b
Vulvar intraepithelial neoplasia (VIN), 991– regeneration and repair in, 103
993, 992f, 992b Wound strength, 110
vWF, von Willebrand factor Woven bone, 1172, 1172f, 1184–1185
vWF metalloprotease, in thrombotic
microangiopathies, 666
VZV, Varicella-zoster virus
X
X chromosome, 146
X-linked agammaglobulinemia, 243–244
W X-linked disorders, 146, 146t
Waardenburg syndrome, 1176t X-linked lymphoproliferative syndrome, 245
Waldenström macroglobulinemia, 607 X-linked muscular dystrophy, with
Wallerian degeneration, 1218 dystrophin mutation, 1232
Warburg effect, 284, 299–302, 302b X-linked severe combined
Warthin tumor, 749–750, 749b–750b, 750f immunodeficiency, 242
Warthin-Finkeldey cells, 350b Xanthogranulomatous pyelonephritis, 930b–
WASP, Wiskott-Aldrich syndrome protein 931b
Water retention, edema due to, 116 Xanthomas, 63
Waterhouse-Friderichsen syndrome, 1122– Xenobiotics, 407, 408f
1123, 1122f–1123f, 1124b Xenografts, 234
in septic shock, 137 Xeroderma pigmentosum, 314, 323, 1148t
Water-soluble vitamins, 436, 443t Xerophthalmia, 437–438
Wear-and-tear pigment, 64–65 Xerostomia, in Sjögren syndrome, 229
Weber-Christian disease, 1166 X-inactivation, 170
Wegener granulomatosis, 705 XIST, 170
Weibel-Palade bodies, in inflammation, 78
Well-defined noninvasive precursor
lesions, 890
Well-differentiated Y
liposarcoma, 1209b, 1210f Y chromosome, 146
Wen, 1143 Yeast infections, 383–385
Wermer syndrome, 1129 Yersinia pestis, 366
Werner syndrome, 67 Yolk sac tumor
Wernicke encephalopathy, 1291, 1291b ovarian, 1025
Wernicke-Korsakoff syndrome, and chronic testicular, 971, 972b
alcoholism, 420
WES, Whole exome sequencing
West Nile virus, 351, 352b Z
WGS, Whole genome sequencing Zellballen, in pheochromocytoma, 1128b
Wheal, 1135t Zenker diverticula, 757
White cells Zika virus infections, 352–353, 353f, 353b
disorders of, 586–628 Zinc, deficiency of, 1223
neoplasia, etiologic/pathogenetic factors Zollinger-Ellison
in, 590–592, 591f syndrome, 773, 1114, 1114b
neoplastic proliferations of, 590–592 Zonule, 1306f
reactive proliferations of, 587–590 Zoonotic infections, 342
WHO, World Health Organization Zuska disease, 1040
Whole exome sequencing (WES), 186–187 Zygomycosis, 387–388, 388b
Whole genome sequencing (WGS), 187
Wickham striae, 1158b
Wilms tumor, 480–483
clinical features of, 483
morphology of, 482f, 482b
pathogenesis and genetics of, 481–482
Wilson disease, 850–851, 850b, 852b
Wiskott-Aldrich syndrome, 246
Wiskott-Aldrich syndrome protein
(WASP), 246
Wnt protein ligands, 19
WNT signaling pathway, 1074
APC in, 297, 298f
Wood smoke, in indoor air pollution, 410
Workload
decreased, 59
increased, 57
Work-up, diagnostic, 714
World Health Organization (WHO), criteria
for the metabolic syndrome, 846t
Wound healing, cutaneous
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