APPROVED by the Academic Council of Kharkiv National Medical University as a textbook

KyivAUS Medicine Publishing20192019

Edited by Professor I.V. SOROKINA,Professor V.D. MARKOVSKYI,Associate Professor D.I. HALATA

Pathomorphology

Approved by the Academic Council of Kharkiv National Medical University as a textbook (minutes No. 2, 22 February 2018)

Au tho r s :I.V. Sorokina, V.D. Markovskyi, D.I. Halata, A.F. Yakovtsova, M.S. Myroshnychenko,

O.M. Pliten, S.M. Potapov, T.V. Bocharova, O.V. Kaluzhyna

Rev i ewe r s :V.O. Tumanskyi — Doctor of Medical Sciences, Professor of the Department of Patho-i

logic Anatomy and Forensic Medicine with Bases of Law of Zaporizhzhia State Medical University;

O.S. Protsenko — Doctor of Medical Sciences, Professor, Head of the Department of General and Clinical Pathology of V.N. Karazin Kharkiv National University

UDC 616-091(075.8)LBC 52.5ya73 P31

Pathomorphology : textbook / I.V. Sorokina, V.D. Markovskyi, D.I. Halatayet al. ; edited by I.V. Sorokina, V.D. Markovskyi, D.I. Halata. — Kyiv : AUSMedicine Publishing, 2019. — 328 p. + 2 colour inserts (8 p. + 12 p.).

ISBN 978-617-505-738-4

The textbook is written by a group of authors of the pathological anatomy department of Kharkiv National Medical University. The modern actual information on general and special pathomorpholo-gy is presented in English. The textbook consists of two parts. The first part is devoted to general patho-logical processes: damage of cells and tissues, regeneration and adaptation, circulation disorders, in-flammation, immune pathology, basics of oncology and tanatology. The second part covers the patho-morphology of diseases according to the nosological principle. The morphological manifestations of pathological processes are described using the newest research methods at the organ, tissue, cellular and subcellular levels, with high-quality illustrations (see colour inserts) of macro- and microspeci-mens. The edition is supplemented with the chapter Oral Pathology, which allows it to be of use for students of the dentistry faculty.

For English-speaking students of higher medical education establishments of Ukraine in the spe-cialties “general medicine”, “dentistry”.

UDC 616-091(075.8)LBC 52.5ya73

© I.V. Sorokina, V.D. Markovskyi, D.I. Halata, A.F. Yakovtsova, M.S. Myroshnychenko, O.M. Pliten, S.M. Potapov, T.V. Bocharova, O.V. Kaluzhyna, 2019

© AUS Medicine Publishing, design, 2019ISBN 978-617-505-738-4

P31

3

C o n t e n t s

Part 1GENERAL PATHOMORPHOLOGY

Chapter 1. CELL AND TISSUE INJURY ........................................................................................................... 6

1. Intracellular Dystrophies ............................................................................................................102. Stromal-Vascular Dystrophies ....................................................................................................163. Pathology of Pigments (Mixed Dystrophies) .............................................................................234. Mineral Metabolism Disturbances .............................................................................................275. Necrosis. Apoptosis ....................................................................................................................30

Chapter 2. BLOOD AND LYMPH CIRCULATION DISTURBANCES ............................................................35

1. Blood Filling Disturbances ........................................................................................................352. Vascular Permeability Disturbances ...........................................................................................373. Blood Rheology Disturbances ....................................................................................................384. Dic Syndrome ............................................................................................................................415. Shock .........................................................................................................................................k 436. Lymph Circulation Disturbances ...............................................................................................447. Interstitial Fluid Amount Disturbances ......................................................................................44

Chapter 3. INFLAMMATION ........................................................................................................................46

1. Exudative Inflammation.............................................................................................................502. Proliferative Inflammation .........................................................................................................52

Chapter 4. IMMUNOPATHOLOGICAL PROCESSES ..................................................................................56

1. Cells And Organs of the Immune System ..................................................................................562. Immune Response ....................................................................................................................603. Pathomorphology of Immunopathological Processes ...............................................................614. Changes of the Antigen-Stimulated Lymphoid Tissue ...............................................................625. Hypersensitivity Reaction ..........................................................................................................n 626. Autoimmune Diseases ................................................................................................................647. Immune Deficiency Syndromes .................................................................................................66

Chapter 5. TISSUE REPAIR AND ADAPTATION .........................................................................................69

1. Regeneration .............................................................................................................................692. Wound Healing ..........................................................................................................................713. Healing in Specialised Tissues ..................................................................................................734. Adaptation ................................................................................................................................755. Compensation ............................................................................................................................79

Chapter 6. NEOPLASIA ................................................................................................................................81

1. General Characteristics of Neoplasia .........................................................................................812. Mesenchymal Tumours ..............................................................................................................843. Tumours of the Nervous System and Brain Membranes ..........................................................894. Tumours of the Melanin-Forming Tissue ..................................................................................955. Epithelial Tumours ....................................................................................................................976. Cancers of Specific Organs ...................................................................................................... 101

4

Contents

Part 2SYSTEMIC PATHOMORPHOLOGY

Chapter 7. HAEMOPOIETIC AND LYMPHOID SYSTEM PATHOLOGIES .................................................108

1. Red Cell Pathology..................................................................................................................y 1082. White Cell Pathology...............................................................................................................y 1153. Thrombocyte Pathology...........................................................................................................y 123

Chapter 8. CARDIOVASCULAR PATHOLOGIES .......................................................................................124

1. Atherosclerosis ......................................................................................................................... 1242. Ischaemic Heart Disease .......................................................................................................... 1273. Hypertensive Vascular Disease ................................................................................................. 1294. Systemic Diseases of the Connective Tissue with Immune Disturbances (Rheumatic Diseases) .................................................................................................................. 133

Chapter 9. CENTRAL NERVOUS SYSTEM PATHOLOGIES .......................................................................141

1. Cerebrovascular Pathology ...................................................................................................... 1412. Head Injury .............................................................................................................................y 1433. Hydrocephalus ......................................................................................................................... 1454. Demyelinating Diseases ........................................................................................................... 1455. Neurodegenerative Diseases .................................................................................................... 1466. Spongiform Encephalopathies ................................................................................................ 1477. Tumours ................................................................................................................................. 147

Chapter 10. RESPIRATORY SYSTEM PATHOLOGIES ..............................................................................148

1. Acute Respiratory Pathology....................................................................................................y 1482. Chronic Obstructive Pulmonary Diseases ................................................................................ 153

Chapter 11. GASTROINTESTINAL TRACT PATHOLOGIES ......................................................................160

1. Throat and Pharynx .................................................................................................................x 1602. Oesophagus .............................................................................................................................. 1613. Stomach ................................................................................................................................... 1634. Intestines .................................................................................................................................. 1685. Appendix..................................................................................................................................x 1726. Peritoneum .............................................................................................................................. 174

Chapter 12. LIVER, GALLBLADDER AND PANCREAS PATHOLOGIES ...................................................175

1. Liver ........................................................................................................................................r 1752. Gallbladder ............................................................................................................................. 1973. Pancreas ................................................................................................................................. 199

Chapter 13. RENAL AND URINARY TRACT PATHOLOGIES ....................................................................201

1. Glomerulopathies ................................................................................................................... 2012. Tubulopathies .......................................................................................................................... 2083. Pyelonephritis .......................................................................................................................... 2104. Nephrolithiasis ........................................................................................................................ 2125. Polycystic Renal Disease ......................................................................................................... 2136. Nephrosclerosis ........................................................................................................................ 2147. Tumours of the Kidneys .......................................................................................................... 216

Chapter 14. ENDOCRINE SYSTEM PATHOLOGIES ..................................................................................218

1. Pituitary Body..........................................................................................................................y 2182. Adrenal Glands ....................................................................................................................... 2193. Thyroid Gland ......................................................................................................................... 2214. Parathyroid Glands ................................................................................................................. 2235. Diabetes Mellitus ..................................................................................................................... 224

5

Contents

Chapter 15. REPRODUCTIVE SYSTEM PATHOLOGIES ...........................................................................226

1. Male Reproductive System ..................................................................................................... 2262. Female Reproductive System ................................................................................................. 2283. Breast ...................................................................................................................................... 2344. Obstetric Pathology ................................................................................................................ 235

Chapter 16. PRENATAL AND PERINATAL PATHOLOGIES .....................................................................239

1. Prenatal Pathology...................................................................................................................y 2392. Perinatal Pathology..................................................................................................................y 245

Chapter 17. INFECTIOUS PATHOLOGIES .................................................................................................250

1. General Pathology of Infectious Diseases ................................................................................ 2502. Gastrointestinal Tract Infections.............................................................................................. 2513. Viral Diseases ........................................................................................................................... 2554. Rickettsioses ............................................................................................................................. 2665. Tetanus ................................................................................................................................... 2686. Childhood Infectious Diseases ................................................................................................. 2697. Tuberculosis ............................................................................................................................. 2778. Sepsis ....................................................................................................................................... 2849. Syphilis .................................................................................................................................... 28810. Quarantine Infections ............................................................................................................ 29111. Prion Diseases ........................................................................................................................ 29612. Protozoal And Helmintic Diseases ....................................................................................... 298

Chapter 18. ORAL PATHOLOGIES ............................................................................................................303

1. Pathology of the Hard Tooth Tissue ........................................................................................ 3032. Pathologies of the Tooth Pulp and Periodontium.................................................................... 3083. Pathology of the Gums and Periodontium ............................................................................. 3114. Pathology of the Jaw Bones .................................................................................................... 3145. Pathology of the Salivary Glands ............................................................................................. 3226. Pathology of the Lips, Tongue and Soft Tissues of the Oral Cavity ........................................y 325

References .............................................................................................................................. 327

6

C h a p t e r 1

CELL AND TISSUE INJURY

INJURY (alteration) is a change in the cell structure, intercellular substance, tissuesYand organs accompanied by disturbances in their vital activity.

There are different morphological manifestations of an injury in the cells and tissues.Subcellular alteration, which largely occurs as a response to more or less constant stim-uli and intracellular accumulation of a number of substances, due to the disturbances in cellular metabolism or excessive storage, as well as cell death (necrosis and apoptosis)have been described in the cells. Visible changes occur in the cells as a result of noxious agents, the degree of changes varying with the severity of the damaging processes: with minor damage the repair mechanisms change, more severe damage results in cell death. There are a lot of genetic and acquired causes of cell injury.

Genetic causes of cell injury producing disease may result from one of the following abnormalities:

1. Abnormalities of chromosomes.2. Abnormalities of genes carried by chromo somes.3. Disorders with multifactorial inheritance.4. Disorders with variable genetic pattern.

Abnormalities of Chromosomes

There are abnormalities in the number and/or morphology of chromosomes. During meiosis in gametogenesis, two homologous chromosomes rather than mo-

ving to the opposite poles of the dividing cell, instead move to the same side so that onegerm cell receives both chromosomes and the other germ cell receives none. This is re-ferred to as chromosomal nondisjunction. The main examples of chromosomal nondis-junction are: Turner’s syndrome (monosomy 45, XO), Klinefelter’s syndrome (trisomy 47, XXY), Down’s syndrome (trisomy 21 involving autosome 21).

When one homologous chromosome in meiosis or one chromatid in mitosis fails to reach the pole of the dividing cell and is left out of the nucleus of the daughter cell, it iscalled anaphase lag. This results in one normal daughter cell and the other with monosomy.

Great deals of inherited and acquired structural ab normalities of the chromosomeshave been described.

Translation means transfer of a segment of one chromosome to an other nonhomol-ogous chromosome. It may be of either of the following types: (1) balanced translocation,when the two fragments of chromosomes exchange material without any loss of material;(2) Robertsonian translocation, when two acrocentric chromosomes lose their short armsand fuse at the centromere so that eventually the cell is left with 45 chromosomes.

7

CELL AND TISSUE INJURY Chapter 1

Deletion means loss of part of the DNA from a chromosome. Deletion may be fromterminal or middle portion of the chromo some. When both ends of a chromosome arelost and the two damaged ends join together, they form a ring chromosome.

Abnormalities of Genes Carried by Chromosomes

Mendelian disorders are the result of mutation of a single gene of large effect. The term “mutation” refers to heritable alteration in the genome, more often affecting a sin-gle base in the gene so that protein synthesis is interfered with. The common types of mutations are point mutation and frameshift mutation. Mutations may be inherited from aparent, or may occur as a result of environmental influ ence such as radiation, chemicalsand viruses as occurs in carcinogenesis.

The inheritance pattern of genetic abnor malities may be dominant or recessive, au-tosomal or sex-linked. A dominant gene produces its effects, whether combined withsimilar dominant or re cessive gene. Recessive genes are effective only if both genes aresimilar. However, when both alleles of a gene pair are expressed in heterozygote state, itis called codominant inheritance. A single gene may express in multiple allelic formsknown as polymorphism. Genes on Y-chromosome are de terminant for testis and arenot known to cause any sex-linked disorder. Therefore, all sex-linked disorders are, in fact, X-linked disorders. All peo ple carrying abnormal gene pairs for a character are af-fected differently. Penetrance means math ematical expression of mutant gene-character as present in the individual, while variable expressivity is variable expression of mutantgene in the dif ferent individuals.

Disorders with Multifactorial Inheritance

These are disorders which result from the combined effect of genetic composition and environ mental influences. Some normal phenotypic char acteristics have also multi-factorial inheritance, e. g. the colour of hair, eye, skin, height and intelligence. Some ex-amples of disorders where environmental influ ences unmask the mutant genes are: (1) autosomal recessive inheritance: beta thalassaemia, sickle cell anaemia, albinism,Wilson’s disease etc.; (2) autosomal codominant inheritance: HLA antigens, blood groupantigens; (3) autosomal dominant inheritance: family polyposis coli, hereditary sphero-cytosis, neurofibromatosis, Marfan’s syndrome etc.; (4) sex (X)-linked recessive inheri-tance: haemophilia A, diabetes insipidus etc.; 5) sex (X)-linked dominant inheritance:hypophosphataemic rickets, incontinentia pigmenti etc.

The causes of acquired damage of cells are various. Their main groups are the fol-lowing:

1. Hypoxia, i. e. reduced oxygen supply (respiratory disease, cardiovascular disease,anaemia).

2. Physical agents (mechanical trauma, excessive heat or cold, radiations).3. Chemical agents (these continue to increase enormously with the complexity of

industrial processes).4. Toxins (bacteria, plants, animals, e. g. tuberculosis).5. Viruses.6. Abnormal immunological reaction (hypersensitivity states, glomerulonephritis).7. Nutritional deficiencies (vitamin deficiency and malabsorption syndromes).

8

CELL AND TISSUE INJURYChapter 1

CELLULAR REACTIONS TO DAMAGE

Cellular reactions to damage depend on the type, duration and severity of the inju-ry induced. The response can range from a minimal and re versible disturbance of cellvolume to massive irrevers ible swelling with a concomitant loss of cell function, fol-lowed by death. When injury develops rapidly, it is conventionally referred to as “acute injury”. The factor that ultimately determines whether a cell will survive or succumb af-ter injury remains to be unequivocally established. Irreversibility is probably attribut ableto the effect of the loss of several vital functions coupled with increased degradation of intracellular components. Recent studies indicate that in the early stages of cell injury there are significant losses of phospholipids from cell membranes. This leads to func-tional alterations of the cell, presumably resulting from acti vation of intracellular phos-pholipases.

If stress is sufficiently prolonged, the cells will cer tainly die; perhaps this occurs when the synthesis of a certain vital molecule or molecules is sufficiently com promisedthat the renewal of cell substance is critically impaired. In less intense and prolongedforms of stress, termed “chronic injury”, cells are able to adapt to environmental ab-normalities to the extent that they are capable of aug mented rather than diminishedfunction.

Cells may adapt to a pathological (disease) stimulus by extending the three normal physiological adaptive responses:

1. Increased cellular activity — increased functional demand on a tissue can be metby an increase in cell number (hyperplasia), as well as by an increase in cell size (hyper-trophy).

2. Decreased cellular activity — cell atrophy.3. Alteration of cell morphology (degeneration, apoptosis, necrosis).The response of cells to an adverse environment is conditioned by numerous intra-

cellular and extracellular factors. These can be classified into four broad catego ries: ex-tracellular and intracellular milieu, pat tern and degree of metabolic activity, level of cell differentiation and amount and expression of information contained in the ge-nome.

Studies of acute injury caused by a variety of noxious agents on both isolated cellsand tissue have shown a striking similarity in the types and sequence of morphologicchanges, regardless of the nature of the injurious agent. The initial event, occurring al-most immediately after exposure of a cell to a noxious environment, is a loss of cell vol-ume control, which is rapidly followed by a decrease in the optical density of the cyto-plasm because of intracellular swelling (hydropic change) and eventual accumulation of lipid droplets (fatty change). If the noxious agent is particularly toxic, additional alter-ations are seen: violent movements of the plasma membrane followed by the develop-ment of bizarre pseudopodia and blebs of the plasma membrane, nuclear swelling, con-densation of nucleus chromatin (pyknosis), dissolution of the nucleus (karyolysis) and fi-nally lysis of the cell (cytolysis).

Cell death is that state in which cells are incapable of any function, including ener-gy generation, homeostatic control, motility, uptake of materials, synthesis, export cellcommunication and excitability and reproduction.

Educa t i ona l e d i t i on

Sorokina Iryna ViktorivnaMarkovskyi Volodymyr Dmytrovych

Halata Daria Ihorivna et al.

Pathomorphology

Textbook

Edited by Professor I.V. Sorokina,

Professor V.D. Markovskyi,Associate Professor D.I. Halata

Authorized for printing 29 January 2019.Format 70100/16. Offset paper.Times typeface. Offset printing.

28,28 conventional printed sheets.Order No.

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