You are on page 1of 200

1

CRIMEAN STATE MEDICAL UNIVERSITY
NAMED AFTER S.I.GEORGIEVSKY

Digest on pathomorphology

Professor
ALEXANDR ZAGOROULKO
Assistant of professor
TATYANA FILONENKO

Crimea, Simferopol
2007

2
УДК 616-091
Z 16
Рецензенти
І.В.Задніпряний – д.м.н., професор кафедри анатомии КДМУ ім. С.І.Георгієвского
О.Ю.Шаповалова – д.м.н., профессор, завідувач кафедри гістології КДМУ ім. С.І.
Георгієвского
Друкується в авторскій редакції.
О.Загорулько, Т.Філоненко
«Дайджест з патоморфології». – Сімферополь, 2007.-417с. – Мова англ.
ISBN 966-73348-14-8
«Дайджест з патоморфології» (друге видання) підготовлений Академіком Міжнародної
Академії Патології, завідувачем кафедри патоморфології Кримського державного медичного
університету Олександром Загорулько і доцентом кафедри Тетяною Філоненко. Книга містить
короткий огляд головних тем з загальної і клінічної патоморфології відповідно до програми,
затвердженої Центральним методичним кабінетом вищої освіти Міністерства охорони здоров’я
України. Книга розрахована на студентів медичних вузів, які навчаються англійською мовою.
Z 143

Z 143

A.Zagorоulko, T.Filonenko
«Digest on pathomorphology». – Simferopol, 2007. – 417 p.
ISBN 966-73348-14-8
“Digest on pathomorphology” (second edition) is prepared by Academician of International
Academy of Pathology, Head of the Department of Pathology of the Ctimean State Medical
University, professor Alexander Zagoroulko, PhD, MD and assistant of professor Tatyana Filonenko,
PhD. The book includes the quick review of the main topics on general and systemic
pathomorphology.

All rights reserved. This book is protected by copyright. No part of this book may be
reproduced in any form or by any means, including photocopying, or utilized by any information
storage and retrieval system without written permission from the copyright owner.

3

Preface
In the preface to the first edition we stated our motive as follows: “We believe that
communication by verbal and written methods are fundamental basis for study and lerning.
Nevertheless, in the mordern setting where knowledge increases so rapidly and in subject such as
pathology where morphological changes are a major component, we consider that the quick review
has an important facilitating role”.
The first edition of the present book is abridged information about the main topics of the
pathomorphology, which combined the efforts of the scientific achievements of the all
pathomorphologists as in theUkraine and other countries as well.
We have attempted to extract the essential elements from the various pathomorphological
literatures for facilitation of the understanding of pathomorphology. Because pathology is the basis of
our medical practice, or, in the words of Sir William Osler, “As is our pathology, so is our practice.”
This book is expected to fulfil the following goal: as an aid to students to revise the subject
quickly near the examinations in short period of time.

4

PART I. GENERAL PATHOLOGY
INTRODUCTION ON PATHOLOGY
Pathology is scientific study of structure and function of the body in disease. The discipline of
pathology forms a vital bridge between initial learning phase of preclinical sciences and the final
phase of clinical subjects. PATHOLOGY is the study (logos) of suffering (pathos). It is a discipline
involving both basic science and clinical practice and is devoted to the study of the structural and
functional changes in the cells, tissues, and organs that underlie “diseases”.
Pathology studies (1) cause of the disease (etiology), (2) the mechanisms of its development
(pathogenesis), (3) the structural alterations induced in the cells, organs and tissues of the body
(morphological changes), and (4) the functional consequences of the morphologic changes (clinical
significance).

CELLULAR INJURY AND CELLULAR DEATH
Etiology of cellular injury
The causes of cellular injury, reversible or irreversible, may be broadly classified into two large
groups:
1. Genetic causes.
2. Acquired causes.
The acquired causes of disease comprise the vast majority of common diseases and can be
further categorised as the follows:
1. Hypoxia and ischemia.
2. Physical agents (mechanical trauma, thermal trauma, ultraviolet and ionizing radiation, rapid
changes in atmospheric pressure).
3. Chemical agents and drugs.
4. Infectious agents.
5. Immunologic agents.
6. Nutritional derangements.
7. Physiologic factors.

Acute Cell Injury
Reversible cellular injury is characterized with the ability of the cell to return to its normal
state after withdrawal of an acute stress.
Reversible injury is manifested with hydropic swelling of the cell (cellular edema), dilation of
endoplasmic reticulum, and detachment of ribosomes from the granular endoplasmic reticulum,
dissociation of polysomes into monosomes, mitochondria swelling and enlargement, blebs of plasma
membrane, nucleolar alterations with disaggregation of granular and fibrilar elements.
Irreversible cellular injury or cellular death is necrosis and apoptosis.
Morphogenetic mechanisms of intra- and extracellular accumulations
Mechanisms of the development of intra- and extracellular (stromal) degenerations
(dystrophies) are the followings:
1. Infiltration – redundant accumulation (deposition) of metabolites into the cells and
extracellular matrix.
2. Decomposition (phanerosis) – disintegration of membranous structures of the cells and
extracellular matrix.
3. Perverted synthesis - synthesis of abnormal substances in the cells and tissues.
4. Transformation – formation of one type of metabolism‟s products from common initial
substances for proteins, fats and carbohydrates.

Keratoid (horney) degeneration is characterized by increase production of keratin substance. 3. 2. diphtheria. The outcome is negative. Mallory's body or alcoholic hyaline in the hepatocytes is intracellular accumulation of intermediate filaments of cytokeratin. vacuolar. lipid. These cell‟s complexes here and there look like rose color homogenous found forms (“canceromatous perls”). For example: Squamous cell carcinoma with keratinization. Starvation. The groups of keratinized cells can be found in the center of squamous cell carcinoma‟s areas. 4. or a product of abnormal metabolism. The heart. 3.genetically determined diseases at which is observed an inconsistency of enzymic systems in cells. Microscopical descriptions of cells on electronics level: presence of electrondense granules in cytoplasm of the cells. Macroscopical kind of organs at this dystrophy it is determined as “muddy or dim swelling”. An abnormal substance such as mineral. Small clear vacuoles are seen in the cells. keratinic squamous epithelial cells. and high fever. In result enzymopathy there is an accumulation in cells of any products of a metabolism. and esophagus. 2. 5. such as water. Such diseases are named as storage diseases. swollen.g. liver or heart muscle is enlarged. which may be due to: 1. cervix. A pigment or an infectious product. fats and carbohydrates. This process may be local and general. Infections (e. poisons.  Loss of fibrillanty of nucleolus. Intracellular proteinous degenerations There are four kinds of intracellular accumulations of proteins: 1. liver.5 INTRACELLULAR ACCUMULATIONS (PARENCHYMAL DEGENERATIONS OR DYSTROPHIES) Intracellular accumulations are the accumulation of abnormal amounts of various substances in the cells. kidneys are damaged most frequently. Late period of pregnancy. and carbohydrates. The main cause of fatty degeneration is hypoxia. Ultrastructural changes in hydropic swelling include the following:  Dilation of endoplasmic reticulum. tuberculosis). The affected organ such as kidney. The stockpiled substances fall into three categories: 1. kidneys. chemicals. Intracellular fatty degenerations Intracellular fatty degenerations are the abnormal accumulations of triglycerides within parenchymal cells. protein. a myocardium and are characterized by accumulation in their cytoplasm proteins. Hydropic (cloudy. avitaminosis. This dystrophy occurs in kidneys. Leucoplakia means hyperkeratosis in mucosa. because the focal or total colliquative cellular necrosis develops. Leucoplakia may lead to malignization. Parenchymal degenerations occur in functional cells such as: cells of a liver. At a section the organs are dim. 6. burns. A normal cellular constituent accumulated in excess. The cut surface bulges outwards and is slightly opaque. The common causes include bacterial toxins. The outcome is negative.  Mitochondrial swelling. and also enzymopathy . Chronic cardiovascular and chronic pulmonary insufficiency. It is not determined macroscopically. The intracellular keratin may be located in epidermis of skin. liver and myocardium. The cytoplasm of plasma cells shows pink hyaline inclusions called Russell's bodies representing synthesised immunoglobulins. 3. 4. A granular degeneration (dystrophy). It is accompanied by decrease (reduction) of function of enzymic systems and occurrence of structural changes in cells. the intoxication. These vacuoles represent distended cisternas of the endoplasmic reticulum. balloon) degeneration is characterized by accumulation of water within the cell due to cytoplasmic vacuolation. Microscopically: the cells are swollen and the microvasculature compressed. Excess alcohol consumption (most commonly). Hyaline-drop degeneration (dystrophy) is characterized by the aggregation of small proteins granules into cytoplasm of cells. The most often causes of parenchymal dystrophies are hypoxia. the cytoplasm of hepatocytes shows eosinophilic globular deposits of a mutant protein.  Blebs on the plasma membrane. Cachexia. The focal or total coagulative necrosis develops. . 2.

Necrosis or sclerosis may develop. 2. the vacuoles become larger pushing the nucleus to the periphery of the cells (macrovesicular). 9. stained by alcian blue. Epithelial mucin is stained positively with periodic acid-Shiff (PAS). Hepatotoxins (e. Infrequently. Intracellular carbohydrate degenerations Carbohydrates are divided into 3 groups: 1. 2. 3. Glycoproteides are stained blue. as well as by some connective tissues like in the umbilical cord. Morphological features – appearance of glycogen masses as clear vacuoles within the cytoplasm developed with special stain – PAS-reaction. g. In diabetes mellitus . in the liver) which causes its fat infiltration (fatty liver degeneration). The kidneys look like “large white kidney”. Fatty degeneration of the liver  Macroscopically the fatty liver is enlarged with rounded margins. mucoid). 8. Morphological features of fatty change: Fat in the tissue can be demonstrated by frozen section followed by fat stains such as Sudan 3 (red color).  The cut surface bulges slightly and is pale-yellow and is greasy to touch. oil red O and osmic acid. Mucoid change Mucus secreted by mucous glands is a combination of proteins complexes with mucopolysaccharides Mucin. g. There are several special reactions for identification of these carbohydrates. flabby. carbon tetrachloride.  Macroscopically the heart is enlarged. Mucopolysaccharides. while connective tissue mucin does not but is stained positively with colloidal iron. increased free fatty acid synthesis. In the case of cell injury by chronic alcoholism. Mucin is normally produced by epithelial cells of mucous membranes and mucous glands. administration of estrogen. Outcomes of fatty degenerations are seldom reversible. the chambers are stretched.  It is observed in the papillary muscles and trabecules of the ventricles in the form of bands (surrounding the veins).6 7. lipogranulomas may appear. decreased tryglyceride utilisation. however.  Microscopically: there are numerous lipid vacuoles in the cytoplasm of hepatocytes. Certain drugs (e. The cortical substance is gray with yellow drops. The vacuoles are initially small (microvesicular). the enlarged fatty liver may return to normal if the person becomes teetotaler. but with progression of the process. Accumulations of glycogen     Accumulations of glycogen are excessive intracellular deposits of glycogen usually in patients with an abnormality of either glucose or glycogen metabolism. flabby. Best‟s carmine and PAS (periodic acid-Schiff) staining may be employed to confirm the presence of glycogen in cells.  Microscopically we can see dust-like fatty vacuoles in the cardiomyocytes.g. Epithelial mucin is associated with: . chloroform). Staining according to Haile for identification glycoproteides. 3. Glycoproteides (mucin.the prime example of this disorder – the red color granules of glycogen can be found with large magnification in the epithelial cells of Henley‟s loops and in the lumen of kidney‟s canals. Both are. Malnutrition. a glycoprotein. They are enlarged. Polysaccharides (glycogen). decreased fatty acid oxidation to ketone bodies. the hepatocytes laden with large lipid vacuoles may rupture and lipid vacuoles coalesce to form fatty cysts. is its main constituent. Amount of glycogen in the tissues reduces sharply (e. Fatty degeneration of the heart  It is also called “Tiger’s” heart. steroids. many factors are implicated with increased lipolysis. Polysaccharides and mucopolysaccarides are stained dark pink or red. tetracycline). It is called “goose liver”.  At times. An alcoholic who has not developed progressive fibrosis in the form of cirrhosis. 1. and block in lipoprotein excretion.

g. large bowel etc. 3. Cystic fibrosis of the pancreas or mucoviscidosis. Type II is the infantile form in which there is progressive involvement of the central nervous system. while a few cases probably result from deficiency of an activator protein. while the deposits in the neurons consist of gangliosides. of respiratory tract. Storage diseases There are a lot of diseases. Niemann-Pick Disease    This is also an autosomal recessive disorder characterized by accumulation of sphingomyelin and cholesterol. bone marrow and lymph nodes. Obstruction of duct leading to mucocele in the oral cavity.e. The cytoplasm of these cells is abundant. of ovary. . in the Virchow-Robin space. liver. Out of the glycogen storage diseases. Microscopically large number of characteristically distended and enlarged macrophages called Gaucher cells which are found in the spleen. This results in lysosomal accumulation of glucocerebroside (ceramide-glucose) in phagocytes of the body and sometimes in the neurons. which normally cleaves glucose from ceramide. These diseases are called storage diseases or enzymopathy. there are 3 types of Gaucher’s disease: 1. granular and fibrillar resembling crumpled tissue paper. bone marrow and lymph nodes. glucocerebrosidase. stomach. i. 2. alimentary tract. and in the case of neuronal involvement. uterus). liver. chronic appendicitis and gall bladder. or sex-(X-) linked recessive genetic transmission. Clinically. This is the most common type comprising 80% of all cases of Gaucher‟s disease. Majority of the cases (about 80%) have deficiency of sphingomyelinase. A few general comments can be made about all storage diseases:  All the storage diseases occur as a result of autosomal recessive. Gaucher’s Disease This is an autosomal recessive disorder in which there is deficiency of lysosomal enzyme. lipidosis and glycogenoses depends on the defect in the enzyme.). which are due to hereditary factors and connected with metabolism disturbance.7     Catarrhal inflammation of mucous membrane (e. bone pains and pathologic fractures. Type 1 or classic form is the adult form of the disease in which there is storage of glycocerebrosides in the phagocytes of the body. which is required for cleavage of sphingomyelin. g. principally involving the spleen.  Most of the storage diseases are lysosomal storage diseases. or thrombocytopenia secondary to hypersplenism. Morphology   In addition to involvement of different organs and systems (splenomegaly. They have mostly a single nucleus but occasionally may have two or three nuclei. hepatomegaly. Type III is the juvenile form of the disease having features in between type I and type II. lymphadenopathy. The main sources of glucocerebroside in phagocytic cells of the body and sometimes in the neurons are the membrane glycolipids of old leukocytes and erythrocytes. only type II (Pompe‟s disease) is due to lysosomal enzyme deficiency. According to the type of metabolism disturbance storage diseases have been classified into:  Proteinoses  Lipidosis  Glucogenoses The type of proteinoses. The condition presents in infancy and is characterized by hepatosplenomegaly. bone marrow and cerebral involvement). lymphadenopathy and physical and mental underdevelopment. Mucin-secreting tumors (e. The most frequent lipidosis are Gaucher‟s disease. they have systemic involvement like in type I and progressive involvement of the central nervous system (CNS) as in type II. These cells often show erythrophagocytosis and are rich in acid phosphatase. Niemann-Pick disease. a few other features include pancytopenia.

lungs. acid mahase. Microscopic examination shows metachromasia. This condition is inherited as an autosomal recessive disorder due to deficiency of enzyme. etc. glucose-6-phosphatase. These processes are associated with swelling of collagen fibers. Other changes due to deranged glucose metabolism are hyperuricemia. Fibrinoid changes  Fibrinoid swelling is deep irreversible connective tissue disorganization. increased vascular permeability (due to glucosaminoglycans (GAG) action) and plasmorrhagia.8  About a quarter of patients present with familial amaurotic idiocy with characteristic cherry-red spots in the macula of the retina.  The storage of sphingomyelin and cholesterol occurs within the lysosomes. EXTRACELLULAR ACCUMULATIONS (MESENCHYMAL DEGENERATIONS) Mescnchymal (stromal vascular) degenerations develop in the connective tissue as a result of metabolic disturbances in it. Gierke Disease. This is also an autosomal recessive disorder due to deficiency of a lysosomal enzyme. fibrinoid changes. These types of connective tissue disorganization are frequently observed in hypertension. lymph nodes. epicardium. There is defective metabolism of glycogen due to genetic disorders. particularly in the cells of mononuclear phagocyte system. 2. bone marrow. In other cases. heart valves. Pompe’s Disease. infections. most often in the heart and skeletal muscles leading to cardiomegaly and hypotonia. liver. 1. The outcome may be reversible. hyalinosis and amyloidosis. The causes of mucoid swelling. especially after exercise. The first three types are the stages of connective tissue disorganization. The most frequent glycogen storage diseases or glycogenosis are Pompe’s disease. As results. Most prominent feature is enormous hepatomegaly with intracytoplasmic and intranuclear glycogen. the development of fibrinoid swelling is possible. hypoxia. . The disease manifests clinically in infancy with failure to thrive and stunted growth. excess of normal type of glycogen accumulates in the liver and also results in hypoglycemia due to reduced formation of free glucose from glycogen. endocardium.  These cells are located in the spleen. The disease is common in 2nd to 4th decades of life and is characterized by painful muscle cramps. Its deficiency results in accumulation of glycogen in many tissues. Stromal vascular proteinous degenerations Proteinous mesenchymal degenerations occur as mucoid swelling. Mucoid swelling      Mucoid swelling is superficial reversible disorganization of the connective tissue. intestine and brain. Under normal conditions the main substance is basophilic. The outcome of storage diseases is unfavorable because of insufficienty of the respective organ. and detection of myoglobinuria in half the cases. In this case staining with toluidine blue demonstrates reddish coloring. In the majority of cases the arterial walls. fibrinous changes and hyalinosis are the same as they are the stages of one process. fat is metabolized for energy requirement leading to hyperlipoproteinemia and ketosis. Macroscopic appearance is absent. Other features include gout. Mc Ardle’s Disease. diabetes mellitus. rheumatism and other diseases of the connective tissue accompanied by immune disturbances as well as in allergic diseases. skin xanthomas and bleeding tendencies due to platelet dysfunction. The condition occurs due to deficiency of muscle phosphorylase resulting in accumulation of glycogen in the muscle (deficiency of liver phosphorylase). The kidneys are also enlarged and show intracytoplasmic glycogen in tubular epithelial cells. Mc Ardle’s disease and Gierke disease.  The cells of Niemann-Pick disease are somewhat smaller than Gaucher cells and their cytoplasm is not wrinkled but is instead foamy and vacuolated which stains positively with fat stains. articular connective tissue are involved. In the absence of glucose-6-phosphatase. They are immunopathological and autoimmune states.

Microscopic study of the arteries demonstrates thickened walls with sharply narrowed or obliterated lumen. pink appearance in routine histologic sections stained with hematoxilin and eosin. The appearance of the organs is changed a little. P-component constituting the remaining 10% of amyloid. sclerosis or hyalinosis. At first. in the areas of chronic inflammation (e. hyaline is accumulated in subendothelial areas of the vascular wall. AL type of fibril protein is produced by immunoglobulin-secreting cells and is. which gives a homogenous. seen in association with plasma cell dyscrasias. impregnated with plasma proteins. adhesions. Fibril Proteins By electron microscopy the major component of amyloid material (about 90%) consists of meshwork of fibril proteins. 3) compound hyaline. it develops in scars. The main signs are revealed microscopically: the bands of collagen fibers are homogenous. Local hyalinosis in the cardiac valves results in heart defects. B-cell lymphoma. glassy. It may be in chronic mflammation and cancer.9       Fibrinoid is formed as a result of the main substance destruction and more increase in vascular permeability. 2.(greek “hyalos” . therefore. Hyalinosis is classified according to its localization (vascular hyalinosis and connective tissue hyalinosis) and propagation (generalized and localized). AL protein of fibrils consists of polypeptides. Thus. the endothelium. Fibril proteins comprising about 90% of amyloid. especially in the kidney. The outcomes are fibrinoid necrosis. In their walls.  AA (amyloid associated) protein. The stimulus for production of AL-amyloid is some disorder of immunoglobulin synthesis (multiple myeloma). “glazed spleen”). Hyalinosis of connective tissue is usually localized. Three types of vascular hyaline are distinguished depending on the pathogenetie character of its formation: 1) simple. familial Mediterranean fever. basement membranes. Hyaline changes (hyalinosis)           Hyaline changes (hyalinosis) . inflammation. 3. 2) lipohyaline. Metachromasia is not marked due to GAG depolymerization of the main substance. which may be made up of whole immunoglobulm light chains or fragment of light chains. Nature and etiology Amyloid is composed of 2 main types of complex proteins: 1. other plasma cells dyscrasias. fibrinoid swelling. Functional significance of hyalin is different. The outcome of hyalinosis is irreversible. infarction of organs. vascular hyalinosis may lead to atrophy or sclerosis. AA protein consists of polypeptides having 76 amino acids and is derived from larger precursor protein in the serum called SAA (serum amyloidassociated protein). become hyalinized. Chemically 2 major forms of amyloid fibril proteins are identified which have different origins and are seen in distinct clinicopathologic conditions:  AL (amyloid light chain) protein. In long-standing hypertension and diabetes mellitus.transparent. SAA is an acute phase reactant protein synthesised in the liver. its level being high in chronic inflammatory and traumatic conditions. Vascular hyalinosis involves the arterioles and small arteries. glass-like) usually refers to an alteration within cells or in the extracellular matrix. necrosis. and smooth muscle cells are damaged. Fibrinoid swelling may be generalized (in systemic diseases of the connective tissue) and localized (in chronic inflammations). . Amyloidosis Amyloidosis is the term used for a group of diseases characterised by extracellular deposition of fibrillar proteinaceous substance called amyloid. Hyalinosis develops as a result of plasma infiltration. In the plasma SAA circulates in association with HDL3 (high-density lipoprotein). the walls of arterioles. and sclerosis.g. owing to extravasated plasma‟s protein and deposition of basement membrane material. and then it destroys elastic and middle membranes.

Senile cerebral amyloidosis is deposition of amyloid material in the walls of cerebral blood vessels in 60% of people above the age of 70 years. chronic pyelonephritis. Hereditary polyneuropathic amyloidosis is an autosomal dominant disorder in which amyloid is deposited in the peripheral and autonomic nerves. Amyloidosis occurring in these cases is AA type. Morphology . A. Patients of Alzheimer‟s disease also develop amyloid in the senile plaques. bronchiectasis. It is synthesised in the liver and is present in all types of amyloid. chronic osteomyelitis. and less often in the solid abdominal viscera. such as multiple myeloma or other B-cell lymphomas.  -amyloid protein (A) is distinctive from A2m and is seen in cerebral plaques as well as cerebral blood vessels in Alzheimer‟s disease. dermatomyositis and scleroderma). and islet cell tumor of the pancreas.10 Other proteins. 3. Primary amyloidosis. In addition a few other forms of proteins are also found in some types of amyloid  Transthyretin (ATTR) is a serum protein that transports thyroxine and retinol normally while a variant of transthyretin is deposited in familial amyloid polyneuropathies and in senile amyloidosis. According to this classification.  This type of amyloidosis is most common form in the world. autoimmune disorders (rheumatoid arthritis. primary amyloidosis is the high binger of frank plasma cell neoplasia. inflammatory bowel disease (ulcerative colitis and Crohn‟s disease) and some tumors (renal cell carcinoma and Hodgkin‟s disease). B. The deposits are seen in the heart and aorta. leprosy. P-Component The second component of amyloid is non-fibnllar P-component that constitutes about 10% of amyloid material. Familial Mediterranean fever is an autosomal recessive disease.    The second form of systemic or generalised amyloidosis is reactive or secondary in which the fibril proteins contain AA amyloid. bowel. spleen. Localized Amyloidosis    Senile cardiac amyloidosis is seen in 50% of people above the age of 70 years. Endocrine amyloidosis. but this is the most common type of amyloidosis in underdeveloped and developing countries of the world.     Familial amyloidosis is seen in patients with familial Mediterranean fever and familial amyloidotic polyneuropathy. Secondary or reactive amyloidosis occurs as a complication of chronic infectious or noninfectious inflammatory conditions associated with tissues destruction such as tuberculosis. amyloidosis can be divided into 2 major categories each found in distinct clinical settings.  A2-microglobulm (A2m) is amyloid seen in cases on long-term hemodialysis (8-10 years). Some endocrine tumors are associated with microscopic deposits of amyloid in medullary carcinoma of the thyroid. Familial amyloidosis.  Primary amyloidosis associates with plasma cell dyscrasias and conteins AL-protein. The condition is characterised by periodic attacks of fever and polyserositis. skeletal muscle. Systemic Amyloidosis 1. Secondary (reactive) amyloidosis. kidneys and adrenals Secondary reactive amyloidosis is seen less frequently in developed countries due to containment of infections before they become chronic. Secondary amyloidosis is typically distributed in solid abdominal viscera like the liver.  In the 25% to 40% of these cases. 2. skin. It is a glycoprotein resembling the normal serum ar glycoprotein and is PAS-positive Classification of amyloidosis A clinical-pathologic classification is widely used currently.  Primary amyloidosis is often severe in the heart.  Hormone precursor such as procalcitonin and pro-insulin (amyloid endocrine) and keratin has also been reported in amyloid.  This is one of the two types of systemic or generalised amyloidosis.

it compresses the cords of hepatocytes.  Amyloidosis of Heart. If renal manifestations are present. Congo red stain is repeated: in the case of primary amyloid (AL amyloid). Metachromatic stains employed are rosaniline dyes such as methyl-violet and crystal-violet. Pathologic changes in organs Amyloidosis of Kidneys     Amyloidosis of the kidneys is most common and most serious because of ill-effects on renal function. The stain can also be used to distinguish between AL and AA amyloid (primary and secondary amyloid respectively). Otherwise the commonly accessible sites such as rectum.  lmmunohistochemistry. All types of amyloid have affinity for Congo red stain. which impart rosepink coloration to amyloid deposits. painting the cut surface with iodine imparts a yellow color that is transformed to blue violet after application of sulfuric acid. If the deposits are sufficiently large. the amyloid deposits likewise begin close to the tubular epithelial basement membrane. Microscopically. i. kidney is the preferred site for biopsy. the amyloid deposits begin in the walls of the arterioles of the white pulp and may subsequently replace the follicles. are biopsied and are followed by Congo red staining for confirmation. c) The vascular involvement affects chiefly the walls of small arterioles and venules. gingiva. . The deposits in the kidneys are found in most cases of secondary amyloidosis and in about one third cases of primary amyloidosis. The kidneys may be normal-sized. The histologic diagnosis of amyloid is based almost entirely on its staining characteristics:  H & E. Amyloid by light microscopy with haematoxylin and eosin staining appears as extracellular. and more recently abdominal fat.  “Lardaceous spleen”. e.  Congo red. The stain may be used on both gross specimens and microscopic sections amyloid stains an orange color. the Congo red positivity (congophilia) persists while it turns negative for Congo red in secondary amyloid (AA amyloid). Cut surface is pale waxy and translucent. waxy and firm. More recently. Amyloidosis of Liver.  Sulfated alcian blue. The splenomegaly is not marked and cut surface shows characteristic translucent pale and waxy nodules resembling sago grains and hence the name. the deposits initially appear on the basement membrane of the glomerular capillaries. but later as it increases. the affected organs are often enlarged and firm and have a waxy appearance. Diagnosis of amyloidosis Histologic examination of biopsy material is the commonest and confirmatory method for diagnosis in a suspected case of amyloidosis. Cut surface of the spleen shows map-like areas of amyloid. b) In the tubules. enlarged or terminally contracted due to ischemic effect of narrowing of vascular lumina. After prior treatment with permangnate on the section. but later extend to produce luminal narrowing and distortion of the glomerular capillary tuft. Microscopically. immunohistochemical stains can classify type of amyloid. the deposits involve the walls of splenic sinuses and the small arteries and in the connective tissue of the red pulp. homogeneous. The liver is often enlarged pale. structureless and eosinophilic hyaline material  Metachromatic stains (Rosaniline Dyes). the dye reacts with amyloid and undergoes a color change. Amyloid has the property of metachromasia. There is generally moderate to marked splenomegaly (weight up to 1 kg). This is a nonspecitic screening test and imparts blue-green color to amyloid positive areas. The amyloid initially appears in the space of Disse. Amyloid deposition occurs primarily in the glomeruli though it may involve peritubular interstitial tissue and the walls of arterioles as well: a) In the glomeruli.11 Macroscopically. Amyloidosis of Spleen Two patterns are observed: “Sago spleen”. Antibody specific for fibril protein gives positive immunoreactivity. producing narrowing of their lumina and consequent ischemic effects.

Those with immunocytederived amyloidosis have a median survival of 2 years after diagnosis. Medial 4.  Depending on the excess of the patient mass compared to the norm. The heart shows tiny nodular deposits of amyioid underneath the endocardium.  According to the etiology the following types of obesity are defined: 1. which are composed with lipids and fibrotic tissue. which may produce restrictive cardiomyopathy. 3. Upper 3. Rectal and gingival biopsies are the common sites for diagnosis of systemic amyloidosis. 3.  Later. Hypertrophic. As a rule such patients develop ischemic heart disease. It may also be involved in localised form of amyloidosis in very old patients. Endocrine. there may be a pressure atrophy and impaired ventricular function. If the patient's mass increases by 50 . 2. . Hyperplastic. Hereditary in Gierke‟s disease. Involvement of the gastrointestinal tract by amyloidosis may occur at any level from the oral cavity to the anus.12  Heart is involved in systemic amyloidosis quite commonly more so in the primary than in secondary systemic amyloidosis. Amyloidosis of Alimentary tract. Symmetrical 2. 2.3rd degree. The wall of the vessel is thicken everywhere. in hyperplastic due to increase in their number. Sharp reduction in the amount of neutral fat in the whole organism is called cachexia. In hypertrophic type adipose tissue enlarges due to increased volume of fatty cells. If the patient‟s mass increases by 20 -29% we distinguish 1st degree of obesity.  Amyloidosis of the heart may produce arrhythmias due to deposition in the conduction‟s system.  In pancreatic lipomatosis beta-cell atrophy and diabetes mellitus are possible. Stromal vascular fatty degenerations  Stromal fatty infiltration is the deposition of mature adipose cells in the stromal connective tissue.99% . 4. If the patient's mass increases by 30 -49% . 2. Alimentary obesity is also unfavorable for the organism. The condition occurs most often in patients with obesity. 2. Stromal vascular carbohydrate degenerations Stromal vascular carbohydrate degenerations develop due to disturbance of glycosaminoglycans and glycoproteids metabolism. When glycoproteid metabolism is disturbed.  If the connective tissue does not grow. Obesity is a severe complication of mainly endocrine and nervous diseases.  The damage to these organs is most serious. Cerebral.  Subepicardial fat covers the heart as a case. If the patient's mass increases by 100% and more 4th degree of obesity. 4 degrees of obesity are defined: 1.  According to morphological peculiarities of adipose tissue. The prognosis for patients with generalized amyloidosis is poor.2nd degree. invades the myocardial stroma causing atrophy and sclerosis. Secondary. obesity may be 1. heart rupture in the area of fat growth may occur. Disturbance in cholesterol and its esters metabolism causes atherosclerosis. Lower.  There are several types of secondary obesity: 1. but much more it is thicken because of the formation of the atherosclerotic plaque. Primary (idiopathic).  According to the patient's appearance. Local enlargement of adipose tissue (lipomatosis) occurs in Dercum's disease when painful fat nodes appear in the subcutaneous fat of the lower and upper extremities and trunk.  As a rule it is a generalized process when the amount of fat in the depots increases.  The two commonly affected organs are the heart and the pancreas. Alimentary. it may be: 1. 4.

and dermatitis. bone marrow. orange-brown crystal pigment. spleen. It may be congenital and acquired.and splenomegaly. spleen and liver. The mucopolysaccarides accumulate in mononuclear phagocytic cells. endothelial cells. Hemosiderin.  Exogenous pigments introduced into the body from environment. Lipidogenic. Its cause is congenital defect of the enzyme determining GAG metabolism. Ferritin is a ferroproteide. It deposits in blood and urine. Collagen fibers change into mucus-like mass. It‟s formed extravascularly in the center of hemorrhages or foci of necrosis at anaerobic conditions.  Myxomatous change in the dermis in myxedema. keratoleukoma (retina opacity). 2. The material is finely granular and PAS-positive by light microscopy. which is formed by aggregates of ferritin and is identifiable by light microscopy as golden-yellow to brown. bone marrow and lymphatic nodes. Porfirin is precursor of hem. It is located in liver. The condition results in colliquative necrosis with formation of cavities filled with mucus. This disease is characterized by irregular skeleton growth. chiefly connective tissues.13 chromotropic substances are released from the protein bonds. or gargoilism. it‟s taken up by monocytes in the blood and subsequently deposited in the liver and spleen. Pigments derived from hemoproteins appear as a result of physiologic destruction of erythrocytes. Bilirubin is iron-free pigment. hepato. It is characterized by deficiency of specific lysosomal enzyme involved in the degradation of mucopolysaccharides or glycosaminoglycans. in the mononuclear phagocytes of the bone marrow. heart defects.  Myxoid change in the synovium in ganglion on the wrist. 3. which are normal constituents of cells and tissues. soft tissue sarcomas etc. PATHOLOGY OF PIGMENTS Pigments are colored substances. By electron microscopy. Hemosiderin is ferric iron that can be demonstrated by Prussian blue reaction 3. 3. spleen. teeth. Spleen. They accumulate in the main substance of the connective tissue.  Hemomelanin is a brown pigment produced by malarial parasites from hemoglobin. Pathologic pigments 1. Physiologic pigments 1. Proteinigenic. lymph nodes. urine becomes of dark red. inguinal and umbilical hernias. heart and brain. Pigments are generally classified into two broad categories:  Endogenous pigments. 2. Hematin is a brown-black pigment derived from hemoglobin and has 2 types:  Chloric hematin is formed in gastric erosions and ulcers as a result of interaction between hemoglobin and gastric excretion (muriate acid). Hemosiderin is iron-containing pigment. Porphyria develops when porphyrin metabolism is disturbed. kidneys. granular pigment. The most frequent of them are Pfaundler-Hurler disease. Connective tissue mucin is associated with:  Mucoid or myxoid degeneration in some tumors (myxomas). 2. Classification of endogenous pigments 1. bones. Hematoidin is iron-free. Acquired porphyria is . Hemoglobinogenic pigments. Syndrome of MPS manifests in infancy or early childhood and involves multiple organs and tissues. it appears in the swollen lysosomes and can be identified biochemically as mucopolysaccharide. erythema. some of which are normal constituents of cells where as others are abnormal and collect in cells only under special circumstances. smooth muscle cells and fibroblasts. Clinical symptoms are photophobia. “massive” skull.  Neurofibromas. Mucopolysaccharidoses (MPS)        Disturbance of glycosaminoglycans (GAG) is due to hereditary factors as in a storage disease. liver.

 It is characterized by local breakdown of red cells in tissues.results from an excessive breakdown of the red blood cell membrane in a variety of conditions.  It can also occur in patients with chronic ineffective erythropoiesis (such as thalassemia major). Injury of brain may lead to bilirubin encephalopathy (kernicterus). . and in patients requiring repeated blood transfusion. The liver‟s capacity to conjugate it is exceeded. In these conditions the excessive amount of pigment has not pass through the liver for conjugation. e. .14 observed in intoxications.  Hemolytic (familial) jaundice in spherocytosis. viral hepatitis and hypoxic necrosis.  In the lungs hemosiderin-laden macrophages (siderofages) are appropriately referred to as “heart failure cells”.  In each instance the pigment is localized in cells of the reticuloendothelial system. mycoplasma pneumonia. Excessive melanin is also deposited. clostridial infection. Rh incompatibility. The generalized form of this condition also referred to as secondary hemochromatosis. the absorbtion of iron is virtually uncontrolled.  Mechanism of local hemosiderosis is extravascular hemolysis. Intrahepatic jaundice (Hepatocellular jaundice) . pernicious anemia.  The pigment imparts a deep brown color to tissues and organs when it is present in high concentrations. spleen and sometimes in kidneys in cases of hemolytic anemia. Visceral siderosis (systemic hemosiderosis). Pathology of hemosiderin’s metabolism Hemosiderosis Hemosiderosis occurs in two situations: Local hemosiderosis.  Circulating of intravascular toxic substances causing red cell destruction (snake poison).g. Types of jaundice 1. may cause necrosis. Prehepatic jaundice (Hemolytic jaundice) . jaundice appears. . in the brain. and the level of unconjugated bilirubin rises in the plasma. Failure of conjugation may involve:  Hepatocellular jaundice. Pathology of bilirubin’s metabolism Jaundice When the bilirubin content of the serum rises above 34 mmol/l.  An immune reaction. the main ones being: . . The liver is light yellowish-green color of saffron (“saffron liver”).  Leukemia. avitaminosis (pellagra).Heart musle. in internal hemorrhage. 2. a genetic disorder..Skin – mainly around swet glands.  Alcohol ingestion when carried to extremes can lead to hemosiderosis because of the augmentation of iron uptake by alcohol.results from failure both of hepatocytes to conjugate bilirubin and of bilirubin to pass through the liver into the intestine. sepsis).Mesenteric lymph nodes. It can crystallize out in the tissues. which may destroy islet tissue (diabetes mellitus).Liver – usually associated with fibrosis (cirrhosis).  It is seen in the liver.  Incompatible blood transfusion.g.  Hemolytic disease of the newborn.  In hemochromatosis.  Sickle cell anemia. Both of conjugated bilirubin and unconjugated bilirubin increase its amount in blood. e.  It occurs regularly around areas of bruising and hemorrhage. . which include:  A genetic membrane defect. hence this condition is sometimes termed “bronzed diabetes”.Pancreas – associated with fibrosis. and diseases of the liver. The system becomes overload and iron is deposited as hemosiderin in many sites.  Mechanism of systemic hemosiderosis is intravascular hemolysis.  Infections (malaria.

cardiocytes. c) chloasma observed during pregnancy. Nevus is a benign tumor. syphilis. c) acquired focal hypopigmentation from various causes such as leprosy. b) vitiligo is hereditary local hypopigmentation of the skin. . iron or iron oxide. radiation dermatitis. They are highly sensitive to sunlight. cholangioles. d) chronic arsenical poisoning. or bile canaliculi). A dysontogenetic malformation (hamartoma) consisting of nevus cells. phosphorous poisoning. it‟s taken up by adjacent epidermal cells and phagocytic melanophores in the underlying dermis Ultraviolet radiation stimulates the synthesis of melanin. melanosis coli. Pathology of the metabolism of proteinogenic pigments             Melanin is a normal pigment found in the form of fine brown granules in the skin. this is referred as brown atrophy. inflammations.results from an obstruction of the passage of conjugated bilirubin from hepatocytes to the intestine. Focal hyperpigmentation: malignant melanoma. healing of wounds. arsenic. Pathology of the metabolism of lipidogenic pigments    Lipopigments usually include lipofuscin and lipochrom. It‟s frequently presented at birth and grows slowly during puberty. tumors. etc. The liver is dark green. Obstructive jaundice may appear in the following causes:  Stenosis of extrahepatic bile ducts. b) an adrenocortical insufficiency resulting from destruction of the adrenal cortex. Lipofuscin is an insoluble lipid pigment presented in cells of elderly persons and those with mulnutrition or a chronic wasting disease.  Mushroom. d) In Kupffer‟s cells. bile pigments may appear: a) As bile pigment droplets in the hepatocytes. Intrahepatic cholestasis. and neurons.g. congenital intrahepatic occlusion. It is a brown intracellular pigment found in hepatocytes. and hair and sometimes in the meninges and intestine. Melanin is a brown-black pigment synthesized by melanocytes from tyrosine by its oxidation. e. poor vision and severe photophobia. lentigo.15   Drug-induced jaundice. Anthracosis (i. 3. nevus.  Fibrosis involving the small intrahepatic ducts. After secretion of the pigment. Albinism is an inherited generalized disorder of melanin metabolism in which there is a decrease or absence of the pigment in the skin and choroid of the eye. The most commonly inhaled substances are carbon or coal dust.. b) As bile impregnations in necrotic areas. Malignant melanoma is a highly malignant neoplasm that invades normal tissues early and widely and that almost invariably terminates in death.  Gall stones in the major ducts. choroids of the eye.. Organs containing large amounts of lipofuscin are deep brown.  In the liver.  Pancreatic tumor compression. in the heart. Albinos have blond hair. c) As bile casts (bile capillaries. adrenal medulla. e. Posthepatic jaundice (Obstructive jaundice) . Localised hypopigmentation: a) leucoderma is a partial albinism and is an inherited disorder. May be generalized melanin pigmentations: a) Addison‟s disease. deposition of carbon particles) is seen in almost every adult lung and generally provokes no reaction of tissue injury. asbestos and various other organic substances. which is reabsorbed. the bile ducts became distended with conjugated bilirubin. e. disturbance of glucoronide conjugation.g. Conjugated bilirubin is water-soluble and is excreted in the urine. Exogenous pigments Inhaled pigments. or cirrhosis. others are silica or stone dust. Various disorders of melanin pigmentation cause generalized and localized hyperpigmentation and hypopigmentation.

kidneys.  Chronic renal failure. myocardium. Dystrophic calcification refers to the macroscopic deposition of calcium salts in injuried tissues and does not simply reflect an accumulation of calcium derived from the bodies of dead cells. II.  Dead parasites (echinococci). irregular and granular clumps.  Osteomalacia (when the bone becomes soft). It is a hereditary disease in which liver ceruloplasmin production decreases. enzymes. in the pancreas. caudal body. Calcium salts precipitate in different organs. The most frequent disturbances in medical practice are in the metabolism of calcium.  Multiple myeloma. and pigments. potassium. Mineral metabolism disturbance Minerals play an active role in metabolic processes of the human organism. Necrotic tissue. its main cause is hypercalcemia. calcium does not resolve. The outcome is unfavorable.  Multiple fractures of the bones. testes. The state is characterized by development of liver cirrhosis. It may be associated with:  Reduction of calcium excretion from the organism. For identification of calcium salts we usually use special reaction called silver impregnation method or Kossa‟s method. Ingested pigments (tattooing).16 Ingested pigments. They are components of structural elements of cells. Carotenemia is yellowish-red coloration of the skin caused by excessive ingestion of carrots. which is not absorbed:  Old caseous lesions of tuberculosis. Metastatic calcinosis (calcium metastases) reflects deranged calcium metabolism associated with increased serum calcium concentration (hypercalcemia).  Dead fetus (lythopedion). especially fibrous tissue. rock-hard material. cornea (in the cornea it looks like greenbrown ring on its margin of the cornea).  Old collections of pus. arterial walls. degenerative symmetrical changes in the brain in the area of lens nuclei. Chronic lead poisoning may produce the characteristic blue lines on teeth. brain.  Vitamin D intoxication. It may occur in crucial locations. It has systemic character. such as: 1. Ceruloplasmin is alpha2-globulin and can bind copper in the blood. Copper metabolism disturbance      This appears in Wilson-Konovalov disease (hepatocerebral degeneration. Pigments like India ink. Copper blood plasma amount is decreased but is increased in the urine. Tissues undergoing slow degeneration:  Hyaline areas in simple tumors. kidneys. It is often visible to the naked eye.  Lesions of the large intestine (the place of Ca excretion). more frequently in the lungs. cartilage. in the mitral or aortic valves after rheumatic fever with formation of mitral or aortic stenosis or as in atherosclerotic coronary arteries with narrowing of those vessels. copper becomes free from unstable bonds with plasma proteins and sediments in the tissue. and iron. etc. As a result.  Old infarcts.  Tissues in old age. . which may be of endocrine origin in hyperproduction of Parathormone or hypoproduction of Calcitonine. Argyna is chronic ingestion of silver compounds.  Old thrombi. vitamins. gastric mucosa. cinnabar and carbon are introduced into the dermis in the process of tattooing where the pigment is taken up by macrophages and lies permanently in the connective tissue. Calcium deposits are stained black. Calcium metabolism disturbances I.  Hyperparathyroidism. Staining with H&E demonstrates calcium salts as deeply basophilic. hepatolenticular degeneration). Chronic ingestion of certain metals may produce pigmentation. and cortex. and ranges from gritty. sandlike grains to firm. 2. Copper accumulates in the liver. hormones. Dystrophic calcification. pale globe. copper.

inflammation (pyelocystitis.  Bronchial calculi consist of mucus inlayed with calcium. etc. they are acquired or hereditary disturbances of metabolism.e. xantin.  The color depends on their chemical composition: white (phosphates). cholangitis. inflammation. gallbladder. cystin. branching in the kidneys.  Their surface may be either smooth or rough. lenticular. General factors are the main ones. veins (phlebolith). Formation of Stones  Stones or calculi are dense formations freely lying in the cavities of the organs or in the ducts. Compression with a stone may result in necroses in renal pelvis. phosphates. oxalates (calcium oxalate). the hormones of which regulate electrolyte exchange.  Their shape depends on the organs in which they are formed: round in the urinary bladder. Local factors are congestion. . calcium and combined. urolithiasis.urates. facet in the gallbladder (their faces are lapped to each other). hepatolenticular. bedsores. biliary stones may be cholesterol. The immediate mechanism of calculus formation consists of two processes: formation of organic matrix and salt crystallization. Each of these may be primary. cholecystitis.  On cut they may be crystalloid (radial structure). hereditary disease for which attack of weakness and motor paralysis are typical. bronchi. urinary . in the excretory ducts of the pancreas.17   There are 3 forms of the disease: hepatic. perforations.). The outcome is unfavorable. crypts of the tonsils. Potassium metabolism disturbances Increased blood (hyperpotassemia) and tissue potassium amount is observed in Addison’s disease and is associated with the lesion of the adrenal cortex. Potassium deficiency characterizes periodic paralysis.  Stones are most frequently formed in the bile ducts and urinary tract in cholelithiasis.  Their chemical composition is different. yellow (urates). pigment. salivary glands. colloid (stratified structure) and colloidcrystalloid (radial-stratified). dark brown or green (pigment). i. Both general and local factors are important for pathogenesis of calculus formation. intestine (coprolyth).

Liquefactive necrosis occurs also in purulent inflammation due to the heterolytic action of polymorphonuclear leucocytes in pus. and slow in fibrous tissue. The irreversibly damaged nuclei are characterized by one of the following three features: 1. Plasmorrhexis is characterized by decomposition of cytoplasm into clumps due to coagulation. and slightly swollen. Necrosis is defined as focal death along with degradation of tissue by hydrolytic enzymes liberated by cells. . 3.cell digestion by lytic enzymes and denaturation of proteins. Gangrene – develops in organs and tissues having contact with environment. firm. With progression they become more yellowish. Trophoneurotic. and toxic factors). Autolysis can occur in the living body when it is surrounded by inflammatory reaction (vital reaction).irreversible degenerative changes. Liquefied tissue is soft.18 IRREVERSIBLE CELLULAR INJURY: Cell death is a state of irreversible injury. 2. The cells do not lyse. Nuclei disappear and the acidified cytoplasm becomes eosiniphilic. Autolysis is the enzymic digestion of the dead cell due to effect of catalytic enzymes derived from lysosomes. This process is characterised by rupture of nuclear membrane and fragmentation of the nucleus. Then plasmolysis takes place. 5. The most often examples of gangrene are gangrene of low extremities. Also karyolysis may be developed. It is invariably accompanied by inflammatory reaction. when the nucleus dissolves. 2. softer. diffluent and composed of disintegrated cells and fluid. This process is called karyopicnosis. and shrunken. Nuclear changes. Nucleus is decomposed into small granules.reversible changes. Waxy (Zenker‟s) necrosis of muscle may occur at typhoid fever. Sometimes we can observe vacuolization and calcification in the cytoplasm. Necrobiosis . Direct (from influence of mechanical. their outlines are relatively preserved. uterus. Stages of necrosis (or morphogenesis): 1. Vascular or ischemic. e. 3. necrosis and apoptosis). 2. Coagulative necrosis is associated with inhibition of lytic enzymes. Autolysis is rapid in some tissues rich in hydrolytic enzymes such as in the pancreas. reversible degeneration. Indirect (vascular and neurogenous). At electron microscopic level. as a rule. According to the cause: 1. 4. or may occur as postmortem change in which there is complete absence of surrounding inflammatory response. Liquefactive (colliquative) necrosis is marked by dissolution of tissue due to enzymatic lysis of dead cells. and gastric mucosa. After that karyorrhexis develops. Paranecrosis . Plasmolysis is hydrolytic fusion of cytoplasm. disorganization and disintegration of the cytoplasmic organelles and severe damage of the plasma membrane are seen. physical. in addition to the above nuclear changes. Allergic. Types of necrosis    According to the mechanisms of development: 1. chemical. liver and kidney. lungs etc. At first nucleus shrinks and becomes dense. In the cytoplasm. It may occur in the living body as a local change (i. or result in end of the life (somatic death). autolysis. it takes place in the brain when autocatalytic enzymes are released from dead cells. Autolysis (“self-digestion”) is disintegration of the cell by its own hydrolytic enzymes liberated from lysosomes. 3. Typically. 2. 3. Toxic. thus. Necrosis Necrosis is celullar death in the living body in the disease. Foci of coagulative necrosis in the early stage are pale. intermediate in tissues like the heart. Two essential changes bring about irreversible cell injury in necrosis . protein denaturation and coagulation or hydration and colliquation take place. According to the morphological features: 1. 4. Death of cells. 2. Traumatic.

Histologically. apoptotic involves single cells or small clusters of cells. degraded. 4. wet and gas gangrene. faintly basophilic material (soap). Incrustation – replacement of the dead tissue with any other salts except calcium. hyaline like deposition in the vessel‟s wall or on the luminal surface of a peptic ulcer. fat necrosis appears as firm. Morphologic features of apoptosis: 1. 6. as a result of leakage of lipase after acute injury to pancreatic acinar tissue. TABLE 1.does not elicit inflammation. and the fragments are quickly phagocytosed. most commonly from obstruction of pancreatic ducts. which has the staining properties of fibrin. Contrasting features of two main forms of gangrene are summarised in Table 1. In addition. Ossification – the formation of the bone tissue in the necrotic area. Organization – replacement of the dead tissue with connective tissue. Phagocytosis of apoptotic cells or bodies. Fat necrosis is encountered in adipose tissue contiguous to the pancreas and more rarely at distant sites. which contain a white or yellow “cheesy” material (Latin caseum = cheese) that accounts for the name of this lesion. Chromatin condensation. Histologically. 3. Incapsulation – formation of the connective tissue capsula around necrotic area. arterioles in hypertension. in tissues stained with hematoxylin and eosin. Hyaline change – the appearance of the hyaline-like substance in the necrotic area. Cell shrinkage. Formation of cytoplasmic blebs and apoptotic bodies. considerable apoptosis may occur in tissue before it becomes apparent in histologic sections. Suppuration or purulent fusion of necrotic tissues. 4. yellow-white deposits in peripancreatic and mesenteric adipose tissue. which can‟t be autolized.19 There are 3 main forms of gangrene . the outlines of necrotic cells are not preserved. marking it even more difficulty to detect histologically. Infarction – vascular or ischemic necrosis. It is encountered in various examples of immunologic tissue injury. Apoptosis       Apoptosis is a programmed (physiological) death of the cell in the living body. Cystic formation. Petrification – replacement of the dead tissue with calcium salts. and their cytoplasm is filled with an amorphous-appearing. replaced by connective tissue and which is localized among alive tissue. Fibrinoid necrosis is characterised by deposition of fibrin-like material. it occurs in the center of tuberculous granulomas. 2. Histologically. necrotic fat cells are distinguishable as pale outlines. or extruded into the lumen. apoptosis . however. Mutilation – spontaneous tearing. Contrasting features of two main forms of gangrene FEATURE DRY GANGRENE WET GANGRENE . 5. The apoptotic cell appears as a round or oval mass of intensely eosinophilic cytoplasm with dense nuclear chromatin fragments. amorphous material. Because the cell shrinkage and formation of the apoptotic bodies are rapid. peptic ulcer etc. Grossly. Typically. fibrinoid necrosis is identified by brightly eosinophilic.away of the dead tissue.in contrast to necrosis . The remnants of the cells appear as finely granular. Sequestration – formation of sequester. Outcomes of necrosis            Regeneration of tissues – replacement of the dead tissue with a new one. Sequester – fragment of dead tissue. but the tissue has not been liquefied either.dry. Caseous necrosis has features of both coagulative and liquefactive necrosis. Histologically. 7. The contrasting features of apoptosis and necrosis are summarised in Table 2.

Morphology No Inflammatory reaction Inflammatory reaction always present Death of single cells Death of many adjacent cells Cell shrinkage Cell swelling initially Cytoplasmic blebs on membrane Membrane disruption Apoptotic bodies Damaged organelles Chromatin condensation Nuclear disruption Phagocytosis of apoptotic bodies by Phagocytosis macrophages macrophages of cell debris by 4. toxins 3. Definition APOPTOSIS NECROSIS Programmed and coordinated cell Cell death along with degradation of death tissue by hydrolytic enzymes 2 Causative Physiologic agents processes and pathologic Hypoxia. SIGNS OF DEATH. POSTMORTEN CHANGES . Contrasting Features of Apoptosis and Necrosis FEATURE 1. Molecular Lysosomes and other organelles Lysosomal breakdown with liberation changes intact of hydrolytic enzymes and oncossuppressor genes DEATH.20 Site Commonly limbs More common in bowel Mechanisms Arterial occlusion More commonly venous obstruction less often arterial occlusion Macroscopy Organ dry shrunken and black Part moist soft swollen rotten and dark Putrefaction Limited due to very little blood Marked due to stuffing of organ with supply blood Line of Present at the junct on between No clear line of demarcation demarcation healthy and gangrenous part Bacteria Bacteria fail to survive Prognosis Generally better septicemia due Numerous present to little Generally poor due to profound toxemia TABLE 2.

21

Death is the expression of irreversible stopping of the vital activity of organism. With
approach of death a man turns into the dead body or corpse (cadaver).
 There are natural (physiologic), violent death and death after diseases.
 Natural death takes place in senile persons as a result of physiologic wear of organism.
 Violent death is a result of murders, suicides, traumas and accidents.
 Death after diseases is a result of incompatibility of the life with changes that were
provoked by pathological (unhealthy) processes.
 There are clinical and biological death:
1. Clinical death is characterized with stopping of breathing and blood circulation, which are
reversible during some minutes (the time of outliving of the brain cortex). Agony precedes clinical
death and is the result of uncoordinated actions of homeostatic systems during terminal period
(arrhythmia, paralysis of sphincters, convulsions and pulmonary edema).
2. Biological death is irreversible changes of vital activity of organism and beginning of autolytical
processes. The central nervous system dies in the fiirst 5-6 minutes. In other organs and tissues this
process lengthen out to some hours or even days.
Soon after biological death a number of signs of death and postmorten changes appears. They
are the followings:
 coolness of the dead body (algor mortis) develops as the result of stopping of
warnth‟s production in the body and equilization of temperature of dead body and
environment;
 becoming numb of a corpse (rigor mortis) is manifested as condensation of
arbitrary and nonarbitrary muscles because of disappearing of adenosine triphosphate and
accumulation of lactic acid in them. Usually it develops in 2-5 hours after death, spreads to
all muscles of the body to the end of the first day, is kept during 2-3 days and then
disappears;
 putrid drying appears because of evaporation of moisture from the surface of the body. It
may be localized or generalized (mummification). The dimness of cornea and appearance of
dark-brown patches on sclera are connected with this process;
 redistribution of blood in the corpse results in repletion of veins with blood, but
arteries remain almost empty. The postmorten coagulation of veins and cavities of the right
part of the heart takes place. However in the cases of death because of asphyxia the blood
does not coagulate (asphyxia of newborns);
 putrid patches appear because of redistribution of blood in the corpse and depend on its
position. The blood flows down into the veins of the lower parts of the body and
accumulates their. That‟s why putrid hypostases appear in 3-6 hour after death;
 putrifacation of the corpse is connected with processes of autolysis and rotting of the
corpse. Postmorten autolysis appears earlier and is more expressed in glandular organs
which cells are rich in proteolytic enzymes (liver, pancreas, stomach). Patrifacative
processes join quickly to postmorten autolysis because of proliferation of putrifactive
bacteria. Putrifacation intestifies postmorten autolysis, leading to fusion of tissues which
become to be colored in dirty-green color and exhale characteristic putrid smell. Quickness
of corpse‟s aulotysis and putrifacation depends on the temperature of environment.

22

CELLULAR ADAPTATIONS
For the sake of survival on exposure to stress, the cells make adjustments with the changes in
their environment (i. e. adapt). Broadly speaking, such physiologic and pathologic adaptations occur
by
 Decreasing or increasing their size (atrophy and hypertrophy respectively).
 By changing the pathway of phenotypic differentiation of cells (metaplasia and dysplasia).
In general, the adaptive responses are reversible on withdrawal of stimulus.
Atrophy
Atrophy means reduction of the number and size of cells, tissues and organs in living
organism characterized by decrease or stopping their function.
Atrophy may be physiologic and pathologic.
A. Physiologic atrophy. It is a normal process of aging in some tissues:
1. Atrophy of lymphoid tissue in lymph nodes, appendix and thymus.
2. Atrophy of gonads after menopause.
3. Atrophy of brain.
4. Atrophy of bones.
It may be obliteration of the umbilical arteries and arterial duct (Botallow‟s) after birth.
B. Pathologic atrophy may be general and local.
General atrophy is observed in cachexia due to
 Oncologic and chronic diseases.
 Starvation.
 Injury of hypophysis (endocrine cachexia).
 Injury of hypothalamus (cerebral cachexia).
Gross appearance of patients occurs:
 Sharp exhaustion.
 Adipose tissue is decreased and it has brown color.
 Muscles are atrophied; skin is dry and flabby.
 Internal organs are small, brown color and often shrunken.
 Osteoporosis takes place.
Histologically:
 Cells become smaller in size but are not dead cells.
 Shrinkage in cell size is due to reduction in cell organelles.
 Accumulation of lipofuscin around nucleus takes place. Lipofuscin (“wear and tear”
pigment) is a golden yellow pigment representing undigested lipid material derived from
cellular metabolism.
Local atrophy has several types:
1. Ischemic atrophy develops due to insufficiency of the blood supply. Hypoxia stimulates of the
proliferation of fibroblasts and forms sclerosis. For example: small atrophic kidney in atherosclerosis
of renal artery, atrophy of brain in cerebral atherosclerosis.
2. Disuse atrophy (dysfunctional) develops due to reduction of the function of organ: atrophy of
muscles due to immobility, atrophy of the pancreas in obstruction of pancreatic duct.
3. Neuropathic atrophy due to interrupted nerve supply: poliomyelitis, motor neuron disease, nerve
section, and inflammation of facial nerve.
4. Endocrine atrophy: hypopituitarism may lead to atrophy of thyroid, adrenal and gonads;
hypothyroidism may cause atrophy of the skin and its adnexal structures.
5. Pressure atrophy: compression of spine by tumor in nerve root, compression of skull by
meningioma arising from pia-arachnoid, compression of sternum by aneurysm of arch of aorta,
compression of renal tissue by dilated renal pelvic in hydronephrosis, compression of brain tissue by
dilated ventricles in hydrocephalus.
6. Atrophy due to chemical and physical influences. For example: action of the radiation lead to
atrophy of bone marrow and genital organs.
7. Idiopathic atrophy: myopathies, testicular atrophy.
The atrophic tissue may be replaced by fatty ingrowths. Atrophy is reversible provided the cause is
eliminated or deficiencies restored.
Hypertrophy and hyperplasia
Hypertrophy refers to an increase in the size of parenchymal resulting in enlargement of the
organ or tissue, without any change in the number of cells.

23
Hyperplasia is an increase in the number of parenchymal cells resulting in enlargement of
the organ or tissue. Quite often, both hyperplasia and hypertrophy occur together.
Mechanisms of hypertrophy

Hypertrophy of tissue arises due to increase of size of functional cells. Thus, the
hypertrophied organ has no new cells, just larger cells.
 Hypertrophy of tissue arises due to increase of number of functional cells (hyperplasia of
cells).
 Hypertrophy of cells arises due to both increase of size of functional cells and increase of
number of ultrastructural elements. Thus, the increased size of the cells is due not to an
increased intake of fluid, called cellular swelling or edema, but to the synthesis of more
structural components. It is called true hypotrophy.
 False hypertrophy is the increase of the size of organs due to growth of connective
tissue, accumulation of the fluid or fatty tissue. It results in atrophy of organ
(hydronephrosis, hydrocephalus, obesity of heart).
True hypertrophy (hyperplasia) has adaptative and compensative characteristics and may
be physiologic and pathologic:
A. Physiologic hypertrophy (hyperplasia).
1. Neurogumoral (hormonal) hypertrophy: hypertrophy of female breast at puberty,
during pregnancy and lactation, hypertrophy of pregnant uterus, proliferative activity
of normal endometrium after a normal menstrual cycle, prostatic hyperplasia in old
age.
2. Working hypertrophy of skeletal muscle: hypertrophied muscles in athletes and
manual labour.
B. Pathologic hypertrophy (hyperplasia).
1. Neurogumoral hypertrophy develops due to impairment of endocrine functions.
Endometrial glandular hyperplasia following estrogen excess which it occurs by
metrorrhagia; atrophy of testis leads to increase of breast (gynecomastia);
hyperfunction of anterior lobus hypophisis (adenoma) leads to increase skeleton
(acromegaly).
2. Working hypertrophy develops in tissues consisting of stable undivided cells due to
increase of size it one. It may be often in cardiac muscle at some cardiac diseases, such
as: systemic hypertension, aortic valve disease (stenosis and insufficiency), mitral
insufficiency; hypertrophy of smooth muscle: cardiac achalasia (in esophagus), pyloric
stenosis (in stomach), and intestinal stricture; hypertrophy of urine bladder in
adenoma of prostatic glands.
3. Compensatory reparative hypertrophy: regeneration of the liver following partial
hepatectomy, regeneration of epidermis after skin abrasion; hypertrophy of
myocardium in postinfarctional cardiosclerosis.
4. Vicarious (substitutional) hypertrophy: following nephrectomy on one side in a
young patient there is compensatory hypertrophy as well as hyperplasia of the
nephrons of the other kidney.
5. Hypertrophic vegetations develop due to chronic inflammation in mucous
membranes (polyps and condilomas); lymphostasis leads to ingrowth of connective
tissue, examples of false hypertrophy. In wound healing, there is formation of
granulation tissue.
According to stage of adaptation two types of myocardial hypertrophy have been described:
 Concentric. In concentric hypertrophy (clinically, no insufficiency) the musculature is
clearly enlarged, measuring till 1.8 cm, but chambers of the heart are not dilated.
 Eccentric. In eccentric hypertrophy myocardium is enlarged but chambers of the heart are
dilated. This leads to hemodynamic disorder with cardiac insufficiency. It is called
myogenic dilatation.
The affected organ is enlarged and firm. For example: a hypertrophied heart of a patient with
systemic hypertension may weight 700-800 g as compared to average normal adult weight of 350 g.
There is enlargement of muscle fibers as well as of nuclei. At ultrastructural level, there is increased
synthesis.
Metaplasia

24
Metaplasia is defined as a reversible change of one type to another type of adult epithelial or
mesenchymal cells, usually in response to abnormal stimuli, and often reverts back to normal on
removal of stimulus. Metaplasia is broadly divided into 2 types:
A. Epithelial metaplasia. This is the more common type. The metaplastic changes may be patchy or
diffuse and usually result in replacement by stronger but less well-specialized epithelium. Some
common types of epithelial metaplasia following:
 Squamous metaplasia: in bronchus in chronic smokers, in uterine endocervix in
prolapse of the uterus and in old age, in gall bladder in chronic cholecystitis with
cholelithiasis, in prostate in chronic prostatitis and estrogen therapy, in renal pelvis and
urinary bladder in chronic infection and stones; in vitamin A deficiency, apart from
xerophthalmia, there is squamous metaplasia in the nose, bronchi, urinary tract, lacrimal
and salivary glands.
 Columnar metaplasia in which there is transformation to columnar epithelium:
intestinal metaplasia in healed chronic gastric ulcer, conversion of pseudostratified
columnar epithelium in chronic bronchitis and bronchiectasis to columnar type, in cervical
erosion.
B. Mezenhymal metaplasia. Less often, there is transformation of one adult type of mesenchymal
tissue to another.
 Osseous metaplasia. Osseous metaplasia is formation of bone in fibrous tissue, cartilage
or myxoid tissue: in arterial wall in old age, in soft tissues in myositis ossificans, in cartilage
of larynx and bronchi in elderly people, in scar of chronic inflammation of prolonged
duration, in the fibrous stroma of tumor.
 Cartilaginous metaplasia. In healing of fractures, cartilaginous metaplasia may occur
where there is undue mobility.
Dysplasia
Dysplasia means “disordered cellular development”, often accompanied with metaplasia and
hyperplasia, it is therefore also referred to as atypical hyperplasia. Epithelial dysplasia is
characterized by cellular proliferation and cytological changes, which include:
 Hyperplasia of epithelial layers.
 Disorderly arrangement of cells from basal layer to the surface layer.
 Cellular and nuclear pleomorphism.
 Increased nucleocytoplasmic ratios.
 Nuclear hyperchromatism.
 Increased mitotic activity.
The two most common examples of dysplastic changes are the uterine cervix and
respiratory tract.

Healing
Healing is the body response to injury in an attempt to restore normal structure and function.
The process of healing involves 2 distinct processes:
 Complete regeneration (restitution), denoting the replacement of injured cells by
cells of the same type, sometimes leaving no residual trace of the previous injury, and
 Incomplete regeneration (substitution) or replacement by connective tissue, or
fibroplasia, which leaves a permanent scar. In most instances, both processes contribute to
repair. In addition, both regeneration and fibroplasia are determined by essentially similar
mechanisms involving cell migration, proliferation, and differentiations, as well as cellmatrix interactions.
Depending upon their capacity to divide, the cells of the body can be divided into 3 groups:
 Labile cells. These cells continue to multiply throughout life under normal physiologic
conditions. These include: surface epithelial cells of epidermis, alimentary tract, respiratory
tract, urinary tract, vagina, cervix, uterine endometrium, hematopoietic cells of bone
marrow and cells of lymph nodes and spleen.
 Stable cells. These cells decrease or lose their ability to proliferate after adolescence but
retain the capacity to multiply in response to stimuli throughout adult life. These include:
parenchymal cells of organs like liver, pancreas, kidneys, adrenal and thyroid;
mesenchymal cells like smooth muscle cells, fibroblasts, vascular endothelium, bone and
cartilage cells.
 Permanent cells. These cells lose their ability to proliferate around the time of birth.
These include: neurons of nervous system, skeletal muscle and cardiac muscle cells.

The wound starts contracting after 2-3 days and the process is completed by the 14th day. Local factors: infection. and limfoid tissue.25 Forms:    Cellular: bones. . fibrocytes and histiocytes). endocrine organs. vegetative nervous system (VNS). 2. Some components of matrix like type IV collagen. endothelial cells. There is acute inflammatory response with exudation of plasma. Phase of inflammation. Granulation tissue formation The following 3 phases are observed in the formation of granulation tissue. This results in formation of inactive looking scar known as cicatrisation. Granulation tissue formation. 2. This phase consists of 2 main processes: angiogenesis or neovascularisation and formation of fibrous tissue. exposure to ultraviolet light. smooth muscles. 3. Dehydration as a result of removal of fluid. Types: 1. connective tissue. skeletal muscles. hyperregeneration or metaplasia (change in cell type). size and location of injury. Endothelial cell growth factors. 2. Contraction of wounds. 3. mucosa). macrophages. Fibrous tissue formation. Reparative regeneration (complete. 1. As maturation proceeds. 2. and the parenchymal cells of the injured organ. Two processes are involved in repair: 1. Formation of new blood vessels at the site of injury takes place by proliferation of endothelial cells from the margins of severed blood vessels. Phase of clearance. 3. Repair Repair is the replacement of injured tissue by fibrous tissue. poor blood supply to wound. Phase of ingrowth of granulation tissue. Mixed: liver. Contraction of wounds. The process of angiogenesis takes place under the influence of the following: 1. epidermis. neutrophils and some monocytes within 24 hours. Combination of proteolytic enzymes liberated from neutrophils. Physiological regeneration is the process of replacement that occurs due to physiologic necrosis (erythrocytes. mucous membrane. Discovery of myofibroblasts. Contraction of collagen. Pathologic regeneration is the slow (hyporegeneration) or pathologically absence one. 2. The new fibroblasts originate from fibrocytes as well as by mitotic division of fibroblasts. Intracellular: myocardium. more and more of collagen is formed while the number of active fibroblasts and new blood vessels decreases. Repair response takes place by participation of mesenchymal cells (consisting of connective tissue stem cells. lungs. hemopoetic system. type. Wound healing    Healing of skin wounds provides a classical example of combination of regeneration and repair described above. autolytic enzymes from dead tissues cells. foreign bodies including sutures interfere with healing and cause intense inflammatory reaction and infection. and phagocytic activity of macrophages clear of the necrotic tissue. platelets. endothelium. Two types of factors influence the wound healing: those acting locally and those acting in general. kidneys. ganglious cells and central nervous system (CNS). In order to explain the mechanism of wound contraction. exposure to ionizing radiation. incomplete with regenerative hypertrophy) is the regeneration after some pathologic necrosis. pancreas. Some of these fibroblasts have morphologic and functional characteristics of smooth muscle cells (myofibroblasts). Collagen fibrils begin to appear by about 6th day. a number of factors have been proposed: 1. Angiogenesis (neovascularisation). debris and red blood cells.

 Granulation tissue. The basal cells of epidermis from both the cut margins start proliferating and migrating towards incisional space in the form of epithelial spurs. Contraction of wound is an important feature of secondary healing. Implantation (epidermal) cyst. The main bulk of secondary healing is by granulations. nutrition.    Complications of Wound Healing          Infection. Neoplasia. As in primary healing. 2. which then clots and seals the wound against dehydration and infection. Healing by first intention (primary union).  Wound contraction. Incisional hernia. . Surgically incised. Deficient scar formation. Edges of wound are approximated by surgical sutures. By 5th day. This can be accomplished in one of the following two ways: 1. Having extensive loss of cells and tissues. at times infected. which clear off the debris as in primary union. 4.  Presence of infection. The wound is not approximated by surgical sutures but is left open. Excessive contraction. Granulation tissue is formed by proliferation of fibroblasts and neovascularisation from the adjoining viable elements. a few inflammatory cells and epithelialised surface is formed. This occurs within 24 hours with appearance of polymorphs. Epithelial changes.  Epithelial changes. Immediately after injury. new collagen fibrils start forming. Organization. Without much loss of cells and tissue.     Healing by second intention (secondary union) This is defined as healing of a wound having the following characteristics: Open with a large tissue defect. Healing by second intention (secondary union). In 4 weeks. Acute inflammatory response. Pigmentation. There is an initial acute inflammatory response followed by appearance of macrophages. fibroblasts also invade the wound area. Each suture track is a separate wound and incites the same phenomena as in healing of the primary wound. Healing by first intention (primary union) This is defined as healing of a wound. By 3rd day. hematological abnormalities. Hypertrophied scars and keloid formation. the epidermal cells from both the margins of wound proliferate and migrate into the wound in the form of epithelial spurs. 3. Bacterial contamination of an open wound delays the process of healing due to release of bacterial toxins that provoke necrosis. Initial hemorrhage. suppuration and thrombosis. Suture tracks. the space between the approximated surfaces of incised wound is filled with blood. systemic infection. uncontrolled diabetes. the scar tissue with scanty cellular and vascular elements. which has the following characteristics: Clean and uninfected.  Inflammatory phase. not seen in primary healing. 5. Hematological abnormalities. The sequences of events in secondary union are as under:  Initial hemorrhage. The sequence of events in primary union is described below: 1. 2.26   Systemic factors: age.

27 HEMODYNAMIC DISTURBANCES These are considered 2 broad headings Disturbances in the volume of the circulating blood. The organ is deeply congested.  Vacatic (lat.  In arterio-venous fistula. Morphology of congestion Because of the increase in venous blood. These hemorrhages may get organized. With long continued over-distension. etc. These are thrombosis.  Of increasing of amount of erythrocytes. the wall of the venules shows reactive thickening and there is mild intestinal fibrosis of the organs.  development of collateral blood circulation. The dilatation of veins and capillaries due to impaired venous drainage results in passive hyperemia or venous congestion. These macrophages are known as heart failure cells. Arterial or active hyperemia is caused by an increased supply of blood from arterial system. giving them a very firm consistency. whereas the impaired venous drainage is called venous congestion or passive hyperemia. These changes are seen typically in the kidney and spleen. I. II. Phagocytes full of brown pigment migrate into intestinal tissue and to the lymph nodus.  cardiac decompensation. I. congested and brownish in color. The sectioned surface is dark brown. Common arterial or active hyperemia is a result  Of increasing volume of circulating blood (pletora). Pulmonary venous engorgement leads to alveolar hemorrhage. This advanced stage seen more commonly in . embolism. organs become swollen and purplish.  Inflammatory. Hemoglobin from intra-alveolar blood is transformed into hemosiderin. or passive hyperemia. Venous.  Hyperemia after anemia.  Hyperemia and congestion Hyperemia and congestion are the terms used for increased volume of blood within dilated vessels of an organ or tissue the increased volume from arterial and arteriolar dilatation being referred to as hyperemia or active hyperemia. The spleen in early stage is moderately enlarged while in longstanding cases there is progressive enlargement and may weigh up to 500 g to 1000 g. tense and cyanotic (“cyanotic induration of the spleen”). Important additional changes are found in the lungs and liver. like pulmonary fibrosis.  Vacatic. Common congestion or Systemic (General) venous congestion is engorgement of systemic veins. Spleen. which is then phagocytized by macrophages. The affected tissue or organ is pink or red in appearance (erythema). Congestion may be acute or chronic. These include hyperemia and congestion. Sectioned surface is gray tan. – vacuum) because of decreased atmospheric pressure. ischemia and infarction.  compression of venous vessel with tumor or ingrowth of connective tissue.  Collateral. emphysema. the latter being more common and called chronic venous congestion. The lungs are burcly. hemorrhage and shock  Circulatory disturbances of obstructive nature. commonly referred to as congestion. or congestion is caused by impediment to the exit of blood through venous pathway. Lungs. It process in lungs is named as “brown induration” of the lungs. Local arterial hyperemia can be  Angioneurotic – because of dilatation of arteries and arterioles. It can be a result of  left-sided and right-sided heart failure  diseases of the lungs which interfere with pulmonary blood flow. The capillaries and veins are dilated paralytically and filled with blood. Local congestion can be a result of  venous obstruction because of its thrombosis. II. Chronic venous congestion of the spleen occurs in right heart failure and in portal hypertension from cirrhosis of liver. The red pulp shows congestion and marked sinusoidal dilatation with areas of recent and old hemorrhages.

Induration of organs. Thus a severe decrease in the number of platelets (thrombocytopenia) or a deficiency of a coagulation factor (e. 4. irregular. Types of hemorrhages in body cavities     Hemothorax – hemorrhage in the pleural cavity. the remaining liver cells may undergo compensatory hyperplasia. which is usually due to trauma. Following a bruise in association with coagulation defect. Stasis. Capillary. By destruction of the blood vessel‟s wall (f. Purpura or hemorrhagic infiltration .the superficial large extravasations of blood into the skin and mucous membranes. intoxication.28 hepatic cirrhosis is called congestive splenomegaly and is the commonest cause of hypersplenism. Outcomes of congestion:       Edema. Hemopericardium – hemorrhage in the pericardium cavity. The peripheral zone of the lobule is less severely affected by chronic hypoxia and shows some fatty change in the hepatocytes.the accumulation of some erythrocytes in tissue between cells. The liver is enlarged and tender and the capsule is tense. or a coagulation defect. a sequence that reflects the progressive oxidation of bilirubin released from the hemoglobin of degraded of red blood cells. 2.e. Thrombosis.. from esophageal varices. Types of hemorrhages according to the site of origin 1. External hemorrhages may be such as: . The changes of congestion are more marked in the centrolobular zone due to severe hypoxia than in the peripheral zone. The centrolobular hepatocytes undergo degenerative changes. Hematoma . Liver. and eventually centrolobular hemorrhagic necrosis may be seen.a grossly visible localized accumulation of the blood in the soft tissue. bleeding) is a discharge of blood from the vascular compairtment to the exterior of the body or into nonvascular body spaces. Venous. as following a penetrating heart wound. ulcer of stomach. 3. Ecchymoses or bruise .e. By ulceration of the vessel‟s wall (f. Hemoperitoneum – hemorrhage in the abdomen cavity. inherent vessel wall weakness. Arterial. Types of internal hemorrhages     Petechia – a small mucosal or serosal hemorrhage or minute punctate hemorrhage usually in the skin or conjunctiva. due to trauma and rupture of a dissecting aneurysm. pale nodules alternating with areas of fibrosis – so-called cardiac cirrhosis. trauma. Hemorrhage. 2. Cardiac. Hemorrhage Hemorrhage (i. an initially purple discoloration of the skin turns green and then yellow before resolving.e. By diapedesis of erythrocytes because of the increased permeability of the vascular wall (f. necrosis of tumor.g. Chronic venous congestion of the liver occurs in right heart failure and sometimes due to occlusion of inferior vena cava and hepatic vein. Atrophy of organs. hypoxia). factor VIII in hemophylia) is assosiated with spontaneous hemorrhages unrelated to any apparent trauma. 3. pulmonary tuberculosis). Hemoarthrosis – hemorrhage in the joint cavity. Mechanisms of hemorrhages 1. which is usually caused by trauma or surgical operation. Cut surface shows characteristic “nutmeg liver” due to red and yellow mottled appearance. This results in small. It‟s not true cirrhosis and does not causes hepatic failure. If the patient has periods of remission. A good example of an eccxymosis is a “black eye”. rupture of aneurysm).e.

Hemoptyesis is hemorrhage from lungs. and in tissue previously congested (lung. and also increased concentration of water. produced by occlusion of either its arterial supply or its venous drainage. Morphologic features   The primary response of acute ischemia is cellular swelling or edema with dilation of the endoplasmic reticulum. swelling of mitochondria. Types of ischemia     Angiospastic (reflex).  Red (hemorrhagic) infarction is encountered with venous occlusion. infarcts are classified as:  Recent or fresh.  Subtotal (when only a part of the organ is affected). Organization and incapsulation of the hematoma. Outcomes of hemorrhages     Coagulation of the blood. If the duration of ischemia is short. . which occurs when arterial flow is impeded by atherosclerosis or by thrombi. collapse of the great veins. and chloride and decreased concentration of potassium into the cytoplasm. and swelling of lysosomes.  Microinfarct (when observed only microscopically). Compressive. intestinum). whereas acute hemorrhage may lead to serious immediate consequences such as hypovolemic shock. If ischemia persists. gray spleen.  White infarction with hemorrhagic halo (kidneys. infarction. Purulent fusion of the hematoma. Metrorrhagia is hemorrhage from uterus. According to the propagation it may be  Total (when the whole organ is affected). Ischemia Ischemia is a loss of blood supply. the structure and the function of tissue may be restored. and a flabby. or by some other causes.29    Melena is deposition of the blood in the faces (excrement or stool) due to hemorrhage from ulcer of stomach. Ischemia is the most common cause of hypoxia. while loss of upto 50% of blood volume over a period of 24 hours may not be necessarily fatal. When the lesion is continuous. dissociation of polysomes into monosomes. A sudden loss of 33% of blood volume may cause death. Brown cystic formatiom (in cerebral hematoma due to accumulation of hemosiderin). Pathogenesis The process of infarction takes place as follows:  Localised hyperemia due to local anoxemia. However chronic blood loss generally produces an iron deficiency anemia. extensive damage to cytoplasm membranes. atrophy or sclerosis may develop. sodium. polip or ulcer of intestines. irreversible injury ensures with severe vacuolization of the mitochondria including their christae. heart). In cases of death from acute massive hemorrhage. Obstructive. Because of redistribution of blood. in tissue as with double circulation.  Old or healed. Types of infarctions:  Ischemic (white) infarction is encountered with arterial occlusion and in solid tissues (spleen). the most significant postmorten changes are gross rather then microscopic and consists in generalized pallor of tissue. Infarction Infarction is an area of ischemic necrosis within a tissue or an organ. According to their age. shrunken.

 The rate of development of the occlusion. The major determinates include:  The nature of the vascular supply. Causes of stasis:  Physical factors (temperature elevation. a narrow rim of preserved renal tissue under the capsule is spared because it draws its blood supply from the capsular vessels. of the individual.  Chemical factors. Blood pigments. They are columns of erythrocytes sticked together. and most often in the lower lobes. It is white infarction with hemorrhagic halo. Pulmonary infarction is an extremely common complication in a variety of clinical settings. Stasis may be discirculatory as a result of venous hyperemia or ischemia. Splenic infarction results from occlusion of the splenic artery or its branches. Following this. This infarction shows coagulative necrosis of myocardial cells. vascular permeability increase. Stasis Stasis (stasis . they are pale or anemic and wedge-shaped with base resting under the capsule and apex pointing towards the medulla. Almost no blood is seen in the vessels. which is called prestasis. The peripheral portion of the infarction has been invaded by acute inflammatory cells. It is characterized by sticking of erythrocytes. They are characteristically pale or anemic and wedge-shaped with their base at the periphery and apex pointing towards hilum. the affected part becomes swollen due to edema and hemorrhage. Renal infarcts are often multiple and may be bilateral. Ischemic necrosis (gangrene) of the lower extremities is a relatively unusual clinical problem in the population at large but is a major concern in diabetes melitus.  Infectious-allergic factors. long one causes hyaline thrombi formation. . found in upto 5% of autopsies.e. The nuclei of muscle‟s fibers and stroma cells are absent. Splenic infarcts are often multiple. edema. though not always. Occlusion of an artery or vein may have little or no effect on the involved tissue or it may cause death of the tissue and. An acute inflammatory reaction and hyperemia appear at the same time in the surrounding tissues. The affected area shows characteristic coagulative necrosis of renal parenchyma i. Characteristically. Old organized and healed pulmonary infarcts appear as retracted fibrous scars.stop) is arrest of blood flow in the vessels of microcirculatory system (capillaries). bleeding. leukocytes and thrombocytes to each other. Cellular changes such as cloudy swelling and degeneration appear early. Short stasis is reversible. which is accompanied by blood viscosity increase.  Autoimmune factors. Clinical significance of infarction Most of the cardiovascular deaths result from myocardial and cerebral infarction. Embolism of the pulmonary arteries may produce pulmonary infarction.  Infection. there are shadows of renal tubules and glomeruli without intact nuclei and cytoplasmic content. variable in size.  The vulnerability of the tissue to hypoxia. Fibrinous pleuritis usually covers the area of infarct. Infarction of the lungs. cold). Sludge syndrome (phenomenon) is regarded as a type of stasis. There is progressive autolysis of the necrotic tissue and hemolysis of the red cells. which act as scavengers and remove the dead cells. hemorrhagic. Coagulative necrosis and inflammatory reaction are seen. there is progressive ingrowth of granulation tissue from the margin of the infarct.30       Within a few hours. Renal infarction is common. indeed. liberated by hemolysis is deposited in the infarct. Cut surface is dark purple and may show the blocked vessel near the apex of the infarcted area. It is classically irregular shape with hemorrhagic infiltration. Morphologic manifestations Myocardial infarction usually develops due to thrombosis of coronary artery. The capillaries and veins are dilated paralytically and filled with blood. The pulmonary infarcts are classically wedge-shaped with base on the pleura. Infarction of the spleen is one of the common sites for infarction. The characteristic feature is coagulative hemorrhagic necrosis of the alveolar walls. In the lumen of some capillaries the homogenous eosinophilic masses can be seen. Generally. hematoidin and hemosiderin.

31
Isolated vein spasm may cause leukostasis, accumulation of erythrocytes within venules (small
veins) and capillaries. It is observed in hypoxia. In shock, leukostasis may be generalized, but as a rule
it is localized in the venules.
Microcirculation disturbances. There are four links in microcirculation:
1. The link of inflow and distribution of the blood (arterioles and precapillaries).
2. Intermediate (exchange) link (capillaries).
3. Depot link (postcapillaries and venules).
4. Drainage link (lymphatic capillaries and postcapillaries). The function of
microcirculation is exchange between the blood and tissue. Pathology of
microcirculatory system is formed of vascular, intravascular and extravascular
changes.
Vascular changes are those in the thickness and shape of the vessels, angiopathies with
disturbance of vascular permeability as a result of hypoxia.
Intravascular changes manifest as different disturbances of blood rheology (sludge, prestasis,
stasis). They are observed in shock of different origin.
Extravascular changes are perivascular edema, hemorrhage, lymphostasis on the lymph
vessels.

Thrombosis
Thrombosis is a pathologic process, which denotes the formation of a clotted mass of blood
within the noninterruptured vascular system.
Influences predisposing to thrombosis:
1. Injury to endothelium;
2. Alterations in the normal blood flow;
3. Alterations in the blood coagulation system (hypercoagulability).
Mechanisms of formation




Agglutination of platelets. Platelets adhere to the endothelium and to each other forming a
projecting mass;
Agglutination of erythrocytes. If the rate of the blood flow is slow, as in veins, red cells are
entangled so that the lumen is occluded;
Coagulation of fibrinogen. In front and behind the platelet mass the blood stagnates.
Further formation of fibrin takes place resulting in a large solid coagulum. The thrombus
extends in either direction to the nearest junction;
Precipitation of plasma proteins. With a slow blood flow in the joining vessel more fibrin is
formed by the platelets at the tip of the thrombus, thus occluding the joint vessel. Blood
stagnates in the joining vessel and thrombosis forwards to the next joining vessel. There
may be a succession of thrombotic episodes – a propagating thrombus.

Types of thrombi
According to the degree of the lumen obstruction, thrombi may be:
Occlusive thrombi most commonly develop in small arteries and veins.
Wall-attached or parietal thrombi develop in large arteries and heart cavities.
Axial.
Globe-shaped (in the heart).
According to the morphology
Thrombi may be of various shapes, size and composition depending upon the site of origin and
it is attached to the vascular wall; it is dense, with corrugated surface. It is composed of branching
bars of stuck thrombocytes and bands of fibrin with erythrocytes and leukocytes located between
them.




Morphological types of thrombi



White thrombus – consists mainly of platelets, fibrin and leukocytes; forms slowly in
rapid circulation of the blood (usually in the arteries);
Red thrombus – consists of platelets, fibrin and excessive amount of erythrocytes; forms
rapidly at slow blood circulation (usually in veins). Venous thrombi are dark-red colored
dry masses with dim surface.
Mixed or laminated thrombus – has laminated structure, contains white and red
elements of thrombus (usually forms in veins, aneurysms of aorta and heart). Mixed

32
thrombus consists of core or head (white thrombus), body (white and red) and tail (has
construction of red thrombus). Core is connected with endothelium. Mixed thrombus is of
gray-red color with rough dim surface, fixed to the intima of the vessel. Body and tail are
located freely in the vessel‟s lumen.
 Hyaline thrombus consists of precipitating plasma proteins, destructed erythrocytes,
leukocytes and thrombocytes. They do not contain fibrin. They resemble hyaline and are
located in the microcirculatory bed.
 Agonal thrombus – consists of the yellowish fibrin and localizes in the apex of the right
ventricle of the heart and may extend into pulmonary artery. It is formed in the last minutes
of the life when the death occurs slowly. Red clot forms in case of the rapid death.
The distinguishing features between thrombi formed in rapidly-flowing arterial circulation and
slow-moving venous blood are given in Table 3.
TABLE 3. Distinguishing Features of Arterial and Venous Thrombi.

FEATURE

ARTERIAL THROMBI

VENOUS THROMBI

1. Blood flow

Formed in rapidly-flowing blood Formed in slow-moving blood in of arteries and heart
veins

2. Sites

Common in coronary, cerebral, Common in superficial varicose
iliac and femoral arteries
veins, deep leg veins, popliteal,
femoral and iliac veins

3.
Formed following endothelial cell Formed following venous stasis,
Thrombogenesis injury, e.g. in atherosclerosis
e.g. in abdominal operations, childbirth
4. Development

5. Macroscopy
6. Microscopy

7. Effects

Usually mural, not occluding the Usually occlusive, take the cast of
lumen completely, may propagate. the vessel in which formed, may
propagate in both directions.
Grey-white, friable with lines of Red-blue with fibrin strands and
Zahn on surface.
lines of Zahn.
Distinct lines of Zahn composed Lines of Zahn with more abundant
of platelets, fibrin with entangled red cells.
red and white blood cells.
Ischemia leading to infarcts, e.g. Thromboembolism, edema, skin
of heart, brain etc.
ulcers, poor wound healing.

Red thrombi (ante-mortem) have to be distinguished from postmortem clots (Table 4).
TABLE 4. Antemortem Thrombi versus Postmortem Clots

ANTEMORTEM THROMBI
1. Dry, granular, firm and friable
2. Adherent to the vessel wall

POSTMORTEM CLOTS
Gelatinous, soft and rubbery
Weakly attached to the vessel wall

3. May or may not fit their vascular contours Take the shape of vessel or its bifurcation
4. The surface contains apparent lines of
Zahn.

The surface is “chicken fa” yellow covering
the underlying red “currant jell”.

33
Clinical effects of thrombosis
These depend upon the site, rapidity of formation, and nature of thrombi.
1. Cardiac thrombi. Large thrombi in the heart may cause sudden death by mechanical obstruction of
blood flow or through thromboembolism to vital organs.
2. Arterial thrombi. These cause ischemic necrosis of the deprived part (infarct), which may lead to
gangrene. Sudden death may occur following thrombosis of coronary artery.
3. Venous thrombi (Phlebothrombosis). These may cause various effects:
 Thromboembolism.
 Oedema of area drained.
 Poor wound healing.
 Skin ulcer.
 Painful thrombosed veins.
 Painful white leg.
 Thrombophlebitis migrans in cancer.
4. Capillary thrombi. Microthrombi in microcirculation may give rise to disseminated intravascular
coagulation (DIC).
Outcomes of the thrombosis
A.Favourable outcomes:
 Aseptic autolysis (dissolution) by fibrinolytic system, proteinolytic enzymes of macrophages
and leukocytes.
 Organization by the replacement of connective tissue.
 Recanalization is the re-establishment of the vascular lumen through occluding thrombus.
 Incorporation or vascularization means restoration of the circulation in the vessel because
of the formation of the new vessels through the thrombotic mass.
 Petrification or dystrophy calcification – accumulation of the calcium salts in the
thrombotic masses.
B.Unfavourable outcomes:
 Thromboembolism.
 Septic autolysis.
 Propagation with following obstruction of some critical vessel.

Embolism
Embolism is the passage through the venous or arterial circulations of any material capable
of lodging in a blood vessel and they‟re by obstructing the lumen. The transported intravascular mass
detached from its site of origin is called an embolus.
Types of embolism
According to localization:
Small blood circulation.
Large blood circulation.
System of vena portae.
According to the direction of the movement of embolus:
 Orthograde (by blood flow)
 Retrograde (against blood flow). Metastasis of the carcinoma prostate in the spine takes
place.
 Paradoxical (emboli arising in the venous circulation may by pass the lungs by travelling
through an incompletely closed foramen ovale, subsequently blocking flow in systemic
arteries).
According to the material of the embolus:
1. Solid:
 Thromboembolism.
 Atheroembolism.
 Tissue (cellular) embolism due to necrosis of tumor, damaged tissue.
 Bacterial embolism.
 Embolism by parasites.
 Embolism by foreign bodies.
2. Liquid:
 Fat embolism.



34

 Amniotic fluid embolism.
3. Gaseous:
 Decompression sickness (caisson disease).
 Air embolism.
Thromboembolism
A detached thrombus or part of thrombus constitutes the most common type of embolism.
These may arise in the arterial or venous circulation:
The effects of arterial emboli depend upon their size, site of lodgement, and adequacy of
collateral circulation:
 Infarction.
 Gangrene.
 Arteritis and mycotic aneurysm.
 Myocardial infarction.
 Sudden death.
The most significant effect of venous embolism is obstruction of pulmonary arterial
circulation leading to pulmonary embolism.
Pulmonary thromboembolism
Pulmonary embolism is the most common and fatal form of venous thromboembolism in
which there is occlusion of pulmonary arterial tree by thromboemboli. Pulmonary emboli are more
common in hospitalised or bedridden patients. The majority of emboli arise from the deep veins of the
low extremities; most of the fatal ones arise from the ileofemoral veins. Condition that favor the
development of pulmonary thromboembolism are:
 Stasis (heart failure, chronic venous insufficiency).
 Injury (trauma, surgery, parturition).
 Hormonal imbalance (oral contraceptive use).
 Advanced age.
 Immobilization (orthopedic, paralysis, bed rest).
 Sickle cell disease.
Pathogenesis




Detachment of thrombi from any of the above-mentioned sites produces a thromboembolus
that flows through venous drainage into the large veins draining into right side of the heart.
If the thrombus is large, it is impacted at the bifurcation of the main pulmonary artery
(saddle embolus), or may be found in the right ventricle or its outflow tract.
More commonly, there are multiple emboli, or a large embolus may be fragmented into
many smaller emboli.
Paradoxical embolism may occur by passage of an embolus from right heart into the
left heart through atrial or ventricular septal defect.

Consequences of thromboembolism
1. Consequences of pulmonary embolism. These include:
Pulmonary Syndrome (Infarction). The pulmonary syndrome clinically resembles
pneumonia. Pleural effusion is common and often bloody. Pathologically, pyramidal segments of
hemorrhagic infarction are seen at the periphery of the lung. Obstruction of terminal branches
(endarteries) leads to central pulmonary hemorrhage.
Circulatory Syndrome (Without Infarction). Embolism produces pulmonary
hypertension by mechanical blockage of the arterial bed. Reflex vasoconstriction and bronchial
constriction due to release of vasoactive substances may contribute to a reduction in the size of the
functional pulmonary vascular bed. Whether a patient develops the pulmonary or the circulatory
syndrome depends on the thromboembolic load and the availability of circulatory reserve of the
bronchial arteries. Pulmonary hypertension may lead to chronic cor pulmonale and pulmonary
arteriosclerosis. Numerous small emboli may obstruct most of the pulmonary circulation resulting in
acute right heart failure (Acute cor pulmonale).
Massive Pulmonary Embolism. Massive pulmonary emboli typically cause sudden
obstruction of blood flow through one or both of the major pulmonary arteries. The patient often goes
into shock immediately - resumably because of certain: neurologic reflexes - and may die within
minutes. This catastrophe is characteristically precipitated when a patient who has been recuperating
from surgery gets out of bed for the first time.

 Cerebral effects may manifest as vertigo. ligaments and tendons.  Neurological symptoms. The effects of arterial air embolism are certain characteristic features: marble skin due to blockage of cutaneous vessels. This is a specialized form of gas embolism known by various names such as caisson's disease. kidney. left ventricular aneurysm. the effects and sites of arterial emboli are in striking contrast to venous emboli. Some of the fat globules may pass through the pulmonary circulation such as via patent foramen ovale. mitral valve disease. . Decompression Sickness. atrophy and necrosis.  Hypertension. in upright position) and reach the brain.  Causes of arterial embolism include: cardiothoracic surgery and trauma. Acute form occurs due to acute obstruction of small blood vessels in the vicinity of joints and skeletal muscles. coma. Obstruction of arterioles and capillaries by fat globules constitutes fat embolism. The pathologic changes and their effects are:  Ischemia. and sometimes death. renal artery embolism may infarct the entire kidney but more commonly results in small peripheral infarcts.  The “chokes” resulting in acute respiratory distress. it is called fat-tissue embolism. marantic endocarditis). oil red O and osmic acid. myocardial infarction. position of the patient during or soon after entry of air. Two main forms of gas embolism are air embolism and decompression sickness. Atheroembolism. rapidity. cardiomyopathy) or diseased valves (bacterial endocarditis. The condition is clinically characterized by the following:  “The bends”. pallor of the tongue due to occlusion of a branch of lingual artery. inflammation of bones and soft tissues.  Lung involvement. absence of pulse. obstetrical operations.g. Chronic form is due to foci of ischemic necrosis throughout body. especially from aorta. fatty liver. either from high atmospheric pressure to normal level. angiography. and get lodged in the capillaries of organs like the brain. Atheromatous plaques. which are often lodged in the lungs. 2. Consequences of emboli in peripheral arteries. Clinical and morphological features: arterial emboli to the brain cause strokes. Decompression sickness is produced when the individual decompresses suddenly. Air Embolism occurs when air is introduced into venous or arterial circulation. intravenous infusion of blood and fluid. The heart is the most common source of systemic emboli. in the mesenteric circulation they cause infarction of the bowel. embolism of an artery of the legs leads to sudden pain.  Gangrene in the lower limbs.g. General condition of the patient e. skin. Important causes are: trauma. divers' palsy or aeroembolism.35 2.  Other organs like parenchymal cells of the liver and pancreas may show lipidvacuoles. which usually arise from mural thrombi (in atrial fibrilation. Systemic fat embolism. Fat Embolism.  Causes of venous embolism include: operations on head and neck. The air bubbles may ascend into the superior vena cava if the position of head is higher than the trunk (e. may get eroded to form atherosclerotic emboli. as little as 40 ml of air may have serious results. Frozen section is essential for confirmation of globules by fat stains such as Sudan dyes (Sudan black. heart failure of any etiology. coronary artery embolism results in myocardial infarctions. or from normal pressure to low atmospheric pressure. in severely ill patients. coronary or cerebral arterial air embolism may cause sudden death by much smaller amounts of air than in the venous air embolism.  Infarcts in the affected organs. paradoxical air embolism. as the patient doubles up in bed due to acute pain in joints. Consequence of fat embolism: Pulmonary fat embolism. arteriography. Clinical effects of decompression sickness are of 2 types: 1. Sudan III and IV). If the obstruction in the circulation is by fragments of adipose tissue. pancreatitis. arteriovenous shunts in the lungs and vertebral venous plexuses. extrinsic fat or oils introduced into the body. especially the skeletal system:  Vascular necrosis of bones. and a cold limb. air bubbles in the retinal vessels seen ophthalmoscopically. and trauma. Thus. Gas Embolism.  Skin manifestations. The effects of venous air embolism depend upon the following factors: amount of air usually 100-150 ml of air entry is considered fatal.

During labour and in the immediate post-partum period. which caused the shock. infection with E. Endotoxins of gram-negative bacilli have been implicated as the most important mediator of septic shock  Gram-positive septicemia (exotoxic shock) is less common e. Shock Shock is defined as a clinical state of cardiovascular collapse characterized by (1) an acute reduction of effective circulating blood volume and (2) an inadequate perfusion of cells and tissues The final result is hypotension and cellular hypoxia and. adrenal insufficiency). pneumococci caused by endotoxins). congestion. 5. Shock morphology .  Hemorrhagic manifestations due to thrombocytopenia and afibrinogenemia. The attack usually lasts for a few seconds or minutes Secondary of true shok. Primary or initial shok. g. b) Fluid loss e. It can occur immediately following trauma. surgery. Shock developing in hormonal insufficiency (thyrotoxic shock. 6. and is the type described below. This is a stage when the patient suffers from some other stress or risk factors besides persistence of the shock so that there is progressive deterioration. persistent vomitings and severe diarrhea causing dehydration. Neurogenic (in intoxication with hypnotic preparations.  Obstruction to the outflow (pulmonary embolism. In the early stage of shock. Non-progressive (initial compensated reversible) shock. if uncompensated. an attempt is made to maintain adequate cerebral and coronary blood supply by redistribution of blood. myxedema. which occurs due to hemodynamic derangements with hypoperfusion of the cells. no recovery takes place it is called decompensated or irreversible shock. 2. This is the form of shock. ganglioblockers. Notable changes are seen in the lungs such as hemorrhages. Deterioration of the circulation in shock is a progressive phenomenon and can be divided arbitrarily into 3 stages: 1. severe pain or emotional over-reaction such as due to fear. infection with streptococci. This type of shock is the true shock. coli. Severe bacterial infections or septicemia induce septic shock:  Gram-negative septicemia (endotoxic shock. 3. Decompensated (irreversible) shock.  Deficient filling (cardiac tamponade from hemopericardium). Septic. Pathogenesis Stages of Shock. This is achieved by activation of various neurohormonal mechanisms causing widespread vasoconstriction and by fluid conservation by the kidney.  Anaphylactoid reaction to amniotic fluid. This is the most serious. Amniotic Fluid Embolism. The causes of hypovolemia include: a) Severe hemorrhage (external or internal) e.g. According to etiology and pathogenesis shock is classified as: 1. which is commonly referred to as “shock” if not specified. The causes include:  Deficient emptying (myocardial infarction. Cardiogenic. ball valve thrombus). rupture of the heart. Anaphylactic (immediate reaction of hypersensitivity). The cause of death may be a result of the following mechanisms:  Mechanical blockage of the pulmonary circulation. Acute circulatory failure with sudden fall in cardiac output from acute diseases of the heart without actual reduction of blood volume (normovolemia) results in cardiogenic shock. in trauma.) e.  Disseminated intravascular coagulation (DIC). These changes are associated with identifiable amniotic fluid contents within the pulmonary microcirculation.g. in severe burns. the right heart is punctured without taking it out. It is transient and usually a benign vasovagal attack resulting from sudden reduction of venous return to the heart caused by peripheral pooling of blood. unpredictable and unpreventible cause of maternal mortality. Hypovolemic. The cavity of the cardiac sac should be preliminary filled with water. may lead to impaired cellular metabolism and death. When the shock is so severe that in spite of compensatory mechanisms and despite therapy and control of etiologic agent. Pseudomonas and bacteroides. narcotics).36 Diagnosis: at autopsy. the contents of amniotic fluid may enter the uterine veins and reach right side of the heart resulting in fatal complications. g. cardiac arrhythmias). Air discharge and foamy blood are observed. 4. Proteus Klebsiella. crush injury to a limb. sorrow or surprise. and dilatation of right side of the heart. Reduction in blood volume induces hypovolemic shock. 2. Progressive decompensated shock. 3. edema and changes of ARDS.

profuse uterine bleedings.  Shock liver: glycogen amount in the hepatocytes decreases. hemorrhages. Ischemic neurons appear shrunken and have eosinophilic cytoplasm. prothrombin in the blood decreases sharply because they have already been used at the first stage with the resultant consumption coagulopathy. coma and death. hemorrhagic syndrome develops. necroses connected with hypoxia and damaging effect of endotoxins. Intensive transfusion therapy of shock masks clinicomorphological picture.  Shock heart: degeneration and necrosis in cardiomyocytes. Clinical Features The classical features of decompensated shock are characterized by depression of 4 vital processes:  Very low blood pressure. But the constant features are liquid cadaver blood irrespective of the composition of transfused fluids.  Shock lung: atelectasis foci. Renal dysfunction in shock is clinically characterized by a phase of oliguria due to ATN and a later phase of diuresis due to regeneration of tubular epithelium. microthrombosis. Microscopically. fat degeneration. Shock morphology depends not only on the cause of the shock but also on its stage. hydropic degeneration and centrolobular necroses resulting in acute hepatic insufficiency develop.  Shock gastrointestinal: the hypoperfusion of alimentary tract may result in mucosal and mural infarction called hemorrhagic gastroenteropathy.  Shallow and sighing respiration. serous-hemorrhagic edema.    Morphologic features of complications in Shock  Shock kidney: degeneration and necrosis in proximal canals with development of necrotic nephrosis (or symmetrical cortical necroses are possible).  Feeble and irregular pulse. leukemia. and immune organs. With progression of the condition the patient may develop stupor. disturbances of hemodynamic and DIC syndrome are noted. They close the vessel (fibrinoembolism). Combination of renal and hepatic insufficiency is called hepatorenal syndrome. Liquid cadaver blood. The pericellular spaces are dilated because of edema.  Subnormal temperature. which results in acute renal insufficiency. .  Shock brain: Hypoxic changes in the brain. reduction in glycogen amount. Large number of fibrin clots is formed. and necrotic foci. It often develops in complicated pregnancy. large injuries.37 Three main pathological processes are observed in shock: DIC (disseminated intravascular coagulation) syndrome. At the last stages degenerative and necrotic process occurs. At the second stage the amount of thrombocytes. it is characterized by generalized spasms of the vessels. fibrinogen. which is characterized by formation of disseminated blood clots in the microcirculatory bed (often in combination with simultaneous reduction of blood coagulability) causing hemorrhages. stases and thromboses in the microcirculatory bed resulting in acute respiratory insufficiency. So blood composition is a criterion for differential diagnosis. Stages of DIC   At the first stage it is characterized by generalized increase of blood coagulation in the microvessels. anemia. signs of increased vascular permeability in microcirculatory system. Rarification of brain tissue presents.  Similar changes occur in nervous. Blood clots in the cardiac cavities and vessels are characteristic for terminal states of nonshock origin. Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is pathological syndrome. At the early stage. Thus. Hemorrhagic diathesis. endocrine systems. thrombocytopenia. degenerations.50% of cases of asphyxia in premature children. in 36 .

adrenals. In severe cases the three stages develop simultaneously. brain edema. decrease in arterial pressure. shock lung. lungs. According to the presence or absence of inflammation Inflammatory. general changes (like toxicosis or shock) develop. red pulp of spleen. TABLE 5 Differences between Transudate and Exudate FEATURE TRANSUDATE EXUDATE Definition Infiltrate of blood plasma without Edema of inflamed tissue associated changes in endothelial permeability with increased vascular permeability Character Non inflammatory edema Inflammatory edema Protein content Low (less than 3 g/dl): mainly High (more than 3 g/ dl). In thrombosis of larger arteries. Degenerative and necrotic changes develop in parenchymatous organs. Morphological changes in DIC syndrome      Large amount of fibrin thrombi and emboli in the small vessels of the liver. 2. brain. Edema fluid lies free in the interstitial space between the cells and can be displaced from one place to another. DIC results in hemorrhages in different organs.38  At the third stage fibrinolysis activation takes place in response to generalized increase of coagulation occurring at the first stage. placenta. and myocardial infarction. readily albumin. (3) impairment in the flow of lymph. kidneys.e.  Exudate such as in inflammatory edema. opening of arteriovenous shunts. mainly mesothelial cells Many cells (inflammatory as well as and cellular debris parenchymal) Examples Edema in congestive cardiac failure Purulent exudates such as pus Types of edema 1. and (4) renal retention of salt and water. which makes hemorrhagic syndrome more severe. (2) fall of colloid osmotic pressure of the plasma. Mucoid swelling. The differences between transudate and exudate are tabulated in Table 5. According to propagation   . fibrinoid swelling and fibrinoid necrosis with endothelium desquamation in the walls of small arteries. Edema fluid may be:  Transudate. Disturbance in blood clotting is accompanied by stasis. organ pathology prevails. Edema Edema may be defined as abnormal and excessive accumulation of fluid in the interstitial tissue spaces and serous cavities. Under these conditions organ pathology is not distinct. In thrombosis of microcirculatory bed. capillary paralysis. which is more often the case such as in edema of cardiac and renal disease. those in the capsule are most frequent. thymus. vital processes of blood-tissue metabolism stop. low fibrinogen. i. acute renal or hepatic insufficiency. has no coagulates due to high content of tendency to coagulate fibrinogen and other coagulation factors Cells Few cells. Noniflammatory is a result of (1) increase in intravascular hydrostatic pressure.

Oncotic edema results from reduction in colloid-osmotic pressure in the blood plasma. If transudate accumulates in subcutaneous fat it is called anasarca.hydrothorax. prolonged diarrhea). .  Redness (rubor). Inflammation of an organ is usually named by adding the suffix-it is to its Latin name. lymph congestion.  Infective agents (bacteria.  Immunological agents (cell-mediated and antigen-antibody reactions). INFLAMMATION Inflammation is fundamentally a protective response whose ultimate goal is to rid the organism of both the initial cause of cell injury and the consequences of such injury.  Loss of Function (functio laesa). cold. The outcome of edema is favorable. the necrotic cells and tissues.  Hyperergic. 2) those in colloid osmotic pressure of blood plasma.  Pain (dolor). kidneys.  Pulmonary edema is usually confined to the lower lobes.  Chemical agents (organic and inorganic poisons).  Exssudative. the following changes are observed: 1) those in hydrostatic blood pressure. but as a rule one of them prevails.  Edema (tumor). atrophy. The agents causing inflammation may be following:  Physical agents (heat.hydrocele.  Increase in interstitial fluid amount. disturbances of nervous trophism. 4) retention of water and electrolytes. affecting all parts of the body. liver. pathologic conditions of pregnancy (hestosis).  Non-specific. which results in plasma protein exit and its accumulation in the tissues. Localized (hydrothorax or pleural effusion. in the testis . In these diseases.  Edema of the brain (cerebral edema) may be localized to the region of the focal lesions of generalized involving the entire brain. etc. in the abdominal cavity. Localization of edema   Subcutaneous edema of the lower parts of the body is a manifastation of cardiac failure.  Hypoergic. the fluid resolves. mechanical injury). infections. in the heart cavity .  Proliferative (productive). hydroperitoneum or ascitis). These factors accompany each other in the majority of cases. hypertensive crises. e. Lymphogenic edema is caused by lymph congestion.g. as in encephalitis. sclerosis. According to Etiology:  Specific.39   Generalized (anasarca). Electrolyte edema results from retention of water and electrolytes. hydropericardium. in vein thrombosis. Membranogenic edema is associated with the increase in capillary permeability. and the obstruction to the venous outflow of the brain. 3) vascular wall permeability increases. Morphological types:  Alterative.hydropericardium. 3. Reduction in interstitial fluid amount (exicosis) may occur in rapid loss of great amount of fluid (cholera. parasites). Renal edema as a result of renal dysfunction or nephrotic syndrome tends to be generalized.ascites. Types of Inflammation 1. Classic clinical signs of inflammation:  Heat (calor). but prolonged edema can result in degeneration. viruses. Edema develops in the patients with cardiovascular. According to the Type of Tissue Reaction:  Normergic. 2. allergic diseases. radiation. in the pleural cavity . mechanical or congestive edema develops as a result of increase in hydrostatic pressure in microvessels and in fluid filtration.

 Structural changes in the microvasculature that permits plasma proteins and leukocytes to leave the circulation. Acute inflammation Acute inflammation is the immediate and early response to an injurious agent. phlegmon. 7.  Hemorrhagic. empyema).  Fibrinous (croupous and diphtheric).  Suppurative (abscess. and adhesion.  Extravasation of leukocytes from the vascular lumen into the interstitial tissue as a result of the following steps: (1) in the lumen: margination.  Prevailed proliferative inflammation with formation of granulomas. Specific Inflammation: A. Features:  Definite pathogenic organism.  Glanders. and (3) migration in the interstitial tissues toward a chemotactic stimulus. Phagocytosis is the process of engulfment and internalization of foreign agents or injuried cell material and cells that possess this function are reffered to as phagocytic cells.  Vasodilation caused by the release of specific mediators is responsible for the redness and warmth at sites of tissue injury. Types of Proliferative Inflammation:  Interstitial. . Systemic effects of acute inflammation. mucous. Phagocytosis involves three distinct but inter-related steps: (1) recognition and attachment of the particle to be ingested by the macrophage.  With formation of polyps and condylomas. B.  Chronic.  Putrificative.  Stasis with leukocytic orientation along the vascular endothelium (leukocytic margination). Vascular changes in acute inflammation:  Vasoconstriction mediated by both neurogenic and chemical mediator system.  Scleroma. (2) transmigration across the endothelium (diapedesis). 6.  Necrosis of exsudate (primary and secondary).  Increased vascular permeability.  Syphilis.  Changing of tissue reactions. and suppurative).40 4. with subsequent formation of a phagocytic vacuole. Phagocytosis and the release of enzymes by neutophils and macrophages constitute two of the major benefits derived from the accumulation of the leukocytes at the inflammatory focus.  Catarrhal (serous.  Around parasites.  Granulomatous. 5.  Chronic wavy course. leading to the escape of a protein-reach fluid into the interstitium with following edema. According to the Duration:  Acute. (2) its engulfment. Accompanied Diseases:  Tuberculosis.  Emigration of the leukocytes from the microcirculation and their accumulation in the focus of injury.  Serous. Types of Exssudative Inflammation:  Pseudomembranous. (3) killing or degradation of the ingested material. The major components of acute inflammation:  Alterations in vascular caliber that lead to an increase in blood flow.  Subacute.  Mixed.  Leprosy. rolling.

 Fibrinous exudate contains large amount of fibrin. supurative and mixed. A surface inflammation associated with greatly increased secretion of clear mucus. pneumococcus. macrophages.  A fibrinous exudate is characteristic of inflammation in body cavities. meningococcus.  It is localized in mucus and cerous membranes by forming fibrinoid films. autointoxications . usually of the range of 15. anthrax). in lungs at croupouse pneumonia. Suppurative or purulent inflammation.  Causes: streptococcus. in bacterial infections there is neutrophilia.  Shock may occur in severe cases. neutrophils. and in parasitic infestations. and together with necrosed epithelium. seldom in internal organs (serous pneumonia).41 The account of acute inflammation given above is based on local tissue responses. immune complex. herpes. Where the damage is severe.  Serous inflammation locates in serous membranes (polyserositis at rheumatic diseases. burn).000-20.  It is marked by the outpouring of a thin fluid that is derived from either the bloodstream or the secretions of mesothelial cells. However.  This process. Catarrhal inflammation may be serous. Systemic activation of coagulation pathway may occur leading to microthrombi throughout the body and result in DIG. forms false membrane that gives this type of inflammation its name. bowel) to toxins of diphtheria or irritant gases. As a result of denudation of epithelium. Catarrhal inflammation.000/nl. and other debris by macrophages. an example of acute inflammation. however. in viral infections lymphocytosis. when the fibrinous membranes unfix with difficulties. 3.  The skin blister resulting from a bum or viral infections represents a large accumulation of serous fluid. desquamative epithelium). more often.  Usually croupous inflammation develops on the columnar epithelium. respiratory. . Fibrinous inflammation or Pseudomembranous inflammation. Usually.uremia). In this case the fibrinous membranes unfix easily. 4. actual rupture of all blood vessels occurs. Hemorrhagic inflammation.  Lymphangitis-lymphadenitis is one of the important manifestations of localized inflammatory injury. streptococcus.  According to the type of epithelium on which inflammatory process develops and depth of necrosis there are two types of fibrinous inflammation: croupous and diphtheric fibrinous inflammation. plague.  This exudate may be remove by fibrinolysis.  Conversion of the fibrinous exudate to scar tissue (organization) within the pericardial sac will lead either to opaque fibrous thickening of the pericardium and epicardium in the area of exudation or.  Causes: stafiloccocus. to the development of fibrous strands that bridge the pericardial space (obliteration).  Conversion of the fibrinous exudate to scar tissue is called organization.  Serous exudates contain until 2% protein and less quantity cells (neutrophils. in mucus (serous rinitis). shigella. eosinophilia. bleeding and death. in skin (streptococcus infections. pseudomonas aeruginosa.  Diphtheric fibrinous inflammation develops on the squamous or intermediate epithelium. Typhoid fever.  It is inflammatory response of mucous surface (oral. corynebacterium diphtheriae.  Histologically fibrin appears as an eosinophilic network of threads or sometimes as an amorphous coagulum. Morphologic patterns in acute inflammation 1. and macrophages. gonococcus. plasma exudes on the surface where it coagulates. 5. acute inflammation is associated with systemic effects as well as under:  Fever occurs due to bacteriemia.  Outcomes are favorable. with hemorrhage the most striking feature (acute hemorrhagic pneumonia occasionally occurring in fatal cases of influenza. because exudates resolves. induces leucopenia with relative lymphocytosis. Serous inflammation. 2. without any effort. called resolution may restore normal tissue structure.  Leucocytosis commonly accompanies the acute inflammatory reactions. such as the pericardium and pleura. either within or immediately beneath the epidermis of the skin.

42  It is characterized by the production of large amounts of pus or purulent exudate consisting of a lot of neutrophils.  Pus is creamy or opaque in appearance and is composed of numerous dead as well as living neutrophils. This can result in pyemic abscesses or septic infarcts.  Chronic inflammation Chronic inflammation is considered to be inflammation of prolonged duration. In the acute stage. there is infiltration by polymorphs with vasodilatation while long-standing ulcers develop infiltration by lymphocytes.  A cavity is formed which is called an abscess and contains purulent exudate or pus and the process of abscess formation is known as suppuration.  An abscess may be discharged to the surface due to increased pressure inside or may require drainage by the surgeon. It occurs when tissue changes are slight and the cellular changes are reversible. a zone of preserved neutrophils around this necrotic area. myocardium. medium – granulation tissue. Ulcer is a local defect on the surface of an organ produced by inflammation. which cause their effects at the site where they are lodged. lungs.Putrificative is assosiated with anaerobic infection and characterized by numerous necrosis. resulting from very small emboli fragmented from septic thrombus. in which active inflammation. fascias. Phlegmon – a diffuse purulent inflammation.  Carbuncle is seen in untreated diabetics and occurs as a located abscess in the dermis and soft tissues of the neck.  Furuncle is an acute inflammation via hair follicles in the dermal tissues. Fate of acute inflammation The acute inflammatory process can culminate in the following: Complete resolution.  When acute bacterial infection is accompanied by intense neutrophilic infiltrate in the inflamed tissue. fragments of tissue debris and fibrin. The internal wall of abscess is called pyogenic membrane. e. resolution in lobar pneumonia.  Acute abscess has a central region appeared as a mass of necrotic white cells and tissue cells. tendons. vascular-nerves fibres and in subcutaneous fat. Fistula can be formed. necrotic cells.  Progression of the tissue response to chronic inflammation. resolution does not occur but instead healing by fibrous scarring takes place. and attempts at healing are proceeding simultaneously. Pyemia is the dissemination of small septic thrombi in the blood.  Due to tissue destruction.  Cellulitis is a diffuse inflammation of soft tissues resulting from spreading effects of substances like hyaluronidase released by some bacteria.  There are the following types of purulent inflammation: Abscess – localized inflammation.  Chronic abscess has internal pyogenic membrane. and area characterized with vascular dilation.  Progression to suppuration. This takes place when the tissue destruction in acute inflammation is extensive so that there is tissue regeneration but actually there is healing by fibrosis. plasma cells and macrophages with associated fibroblastic proliferation and scarring. This means complete return to normal tissue following acute inflammation. and edema fluid.  It may be densed and soft. it results in tissue necrosis. macrophages and cholesterol crystals are also present. Ulcer. and renal cortex. Acute inflammation may progress to chronic one in which the processes of inflammation and healing proceed side by side. indicating the beginning of repair. external – fibrous tissue membrane. parenchymal and fibroblastic proliferation. Pyemic abscesses are multiple small abscesses in various organs such as in cerebral cortex.  Phlegmon frequently occurs along the muscular fibres. 6. Chronic inflammmation arises under the following settings: . tissue destruction. empyema of gall bladder and urinary bladder and so on). some red cells.g.  Healing by connective tissue replacement (fibrosis). In old pus. 7. Empyema – a purulent inflammation of serous membranes (empyema of pleura.

monocytes. plasmocytes.  Polyps are the end-result of prolonged chronic irritation. tiny lesion. e. However. 2. syphilis. e.  deposition of extracellular matrix.g.  A variant of this type of chronic inflammatory response is chronic suppurative inflammation in which infiltration by polymorphs and abscess formation is additional features. tuberculosis. eosinophils and other cells.g. Types of chronic inflammation: I. histological features are used for classifying chronic inflammation into 3 corresponding types: 1.43     Chronic inflammation following acute inflammation . for a more descriptive classification. Chronic inflammation starting de novo . e. pneumonia terminating in lung abscess. plasmocytes.  migration and proliferation of fibroblasts. leprosy. General features of chronic inflammation 1. Nonspecific. . Chronic nonspecific inflammation. about 1 mm in diameter. composed predominantly of collection of modified macrophages called epithelioid cells.  It is characterized by nonspecific inflammatory cell infiltration. in recurrent urinary tract infection leading to chronic pyelonephritis. infection with Mycobacterittm tuberculosis. 2. sarcoidosis etc. actinomycosis.g.when the tissue destruction is extensive. cervical. In stroma there are hyperemic vessels.g. leprosy. chronic osteomyelitis. e. Chronic granulomatous inflammation. Nasal. e. which include macrophages. colorectal polyps are common. Mononuclear cell infiltration.  Granulomatous inflammation is the distinctive pattern of chronic inflammatory reaction in which the predominant cell type is an activated macrophage with a modified epithelial-like (epithelioid) appearance. Specific. There are four components of this process:  formation of new blood vessels (angiogenesis). 3. chronic osteomyelitis. syphilis.  Condyloma acuminatum is commonly located on the coronal sulcus on the penis or the perineal area.  It is characterized by formation of granulomas.  It occurs on the mucous membranes and in the areas borderline with squamous epithelium. chronic ulcer. Tissue destruction or necrosis is brought about by activated macrophages by release of a variety of biologically active substances. infiltrates of lymphocytes and plasma cells with admixture of leukocytes. eosinophils and mast cells. chronic lung abscess. when the irritant substance produces a non-specific chronic inflammatory reaction with formation of granulation tissue and healing by fibrosis. e.g. immune reactions are set up against the individual‟s own tissues leading to autoimmune diseases.when repeated bouts of acute inflammation culminate in chronicity of the process. and rimmed at the periphery by lymphoid cells. scleroma. actinomycosis. when the injurious agent causes a characteristic histologic tissue response. As a result of necrosis. Recurrent attacks of acute inflammation . lymphocytes and plasma cells. Condyloma is the growth of squamous cell epithelium and connective tissue of the skin with appearance of numerous small papillas on the surface.  maturation and organization of the fibrous tissue. tuberculosis. e. proliferation of small blood vessels and fibroblasts is stimulated resulting in formation of inflammatory granulation tissue. Microscopically they are composed of loose edematous connective tissue containing some mucous glands and varying number of inflammatory cells (lymphocytes. II. Proliferative changes.g. also known as remodeling.  Granuloma is defined as a circumscribed.  The inflammatory cell infiltration consists of lymphocytes. Macroscopically they are gelatinous masses with smooth and shining surface. e. repeated acute infection of gall bladder leading to chronic cholecystitis. eosinophils).g. in osteomyelitis.when the infection with organisms of low pathogenicity is chronic from the beginning. Chronic nonspecific interstitial inflammation with formation of polyps and pointed condyloma. Under certain conditions.g. or the bacteria survive and persist in small numbers at the site of acute inflammation. 3.

the granuloma is reffered to as a tubercle and is classically characterized by the presence of central caseous necrosis surraunded by epitelioid cells. Around gumma forms the granulations tissue and endovasculitis. fungal infections. the epidermis contains confluent granulomas composed of macrophages. Microscopical examination of the non. fibroblasts and single “giant cells of the foreign bodies” can be found. Granulomatous inflammation is typical of reaction to poorly digestible agents elicited by tuberculosis. lymphocytes. 2. Before studying the morphology of immunogenesis disturbance it is necessary to know the normal immune morphology. plasma cells. Fibrosis is due to proliferation of fibroblasts at the periphery of granuloma. and -oma. which is a suffix commonly. central caseation necrosis of tuberculosis. sclerosis and hyalinosis take place. These nuclei may be arranged at the periphery like horseshoe or ring or clustered at the two poles (Langhans’ giant cells). caseous necrosis is rare in other granulomatous diseases. e. The outcomes of chronic inflammation depend on the type of inflammation. Microscopical examination of the spesific granulomas In tuberculosis. and hyaline sphere. In the outside –fibrous capsule. which are associated with disturbances of structure and function of lymphoid tissue. and seldom-giant Langhance‟s cells. plasma cells. etc. The following two factors favour the formation of granulomas: 1. epitelioid cells. limphocytes. which may be organisms like Mycobacterium tuberculosis. 2. The syphilis granuloma is called gumma. where inflammation develops. The progenitor cells produced in the bone marrow circulate to the thymus or peripheral organs . morphofunctional characteristic of the definite organ or tissue. Foreign body granulomas and immune granulomas. lightly-staining slipper-shaped nucleus and the cell membrane of adjacent epithelioid cells is closely apposed. The bone marrow contains progenitor cells for the other lymphoid organs. or they may be present centrally (foreign body giant cells). Epithelioid cells. There is no central necrosis. Necrosis may be a feature of some granulomatous conditions. implying thereby the role of hypersensitivity in granulomatous inflammation. Presence of poorly digestible irritant. so called because of their epithelial cell-like appearance. plasma cells and giant Langhance‟s cells. and leprous Virhov’s cells. particles of talc etc. used for true tumors but here indicates inflammatory mass or collection of macrophages. epithelioid cells. foreign particles.44         The word “granuloma” is composed of granule meaning circumscribed granule-like lesion. Central organs of immune system producing immune-competent cells are bone marrow and thymus. Gumma consists of a central area of fibrinoid or caseous necrosis surrounded by mononuclear inflammatory cells. granulomas may have giant cells. Presence of cell-mediated immunity to the irritant. mostly plasma cells. the granuloma (scleroma) consists of the plasma cells. Large macrophages with light cytoplasm containing Klebsiella rhinoscleromatis (Mikulicz’s cells).spesific granulomas Proliferative inflammation around echinococcus of the liver. are modified macrophages which are somewhat elongated. Leprous Virhov‟s cells (or leprosy cells) refer as large foamy macrophages within fatty vacuoles containing leprous mycobacteriums. IMMUNOPATHOLOGY   Immunopathological processes are pathological states. In peripheral areas crowded lymphocytes. Sarcoidosis. The tissue contains granulomas composed of epithelioid macrofages and only a few lymphocytes and giant cells. leprosy. In contrast. Infectious. lymphocytes. Frequently sclerosis and hyalinosis may develop. Types of granulomas: 1. Besides the presence of epithelioid cells and lymphoid cells. The area of the liver‟s tissue with destructive pink color shined chitinous membrane and surrounded necrotic tissue are seen. In rhinoscleroma of nose.g. In tuberculoid leprosy. and noninfectous. having pale-staining abundant cytoplasm. schistosomiasis. necrosis and fibrosis: The giant cells are formed by fusion of adjacent epithelioid cells and may have 20 or more nuclei.

The weight and the size of thymus are considerably increased. (9) lymphotoxin.transition of the lymphocytes from the cortex to the medullar substance. i. Pathology of Thymus Thymus is the organ regulating the whole immune system. monocytes. Macrophages are dominant participants in subacute and chronic inflammatory reactions. It occurs in the cortex. Stage 4 . Ivanovskaya (1976). intoxications. B-lymphocytes. periarterial zone of the follicle is T-zone. Stage 2 . At this stage Blymphocytes are transformed into plasmoblasts and plasmocytes. Accidental thymus transformation (involution). and medullar layer looks dark as a result of transition of lymphocytes from the cortex to the medullar substance. Thus. Stage 3 – “layer inversion”. (6) interleukin-2. Cellular Components of the Immune Response:  T-cells are thymus-derived lymphocytes and produce (1) B cell growth factor. There are T-. Accidental involution occurs in infections.Reduction in the lymphocyte amount in the both layers. light centers of the follicles age‟s-zone. 1. macrophages without any zones. cortical layer.  Main peripheral organs of immune system are spleen. Transmission of the information is the main function of B-cells. and macrophages.  Natural Killer Cells have capacity to recognize directly and kill various tumors and virusinfected in vitro. Stage 1 – “holey clearing” . (3) colony stimulating factor. (8) leikocyte inhibition factor. in the spleen. the more pronounced is the degree of involution. lymphatic nodes and gastrointestinal associated lymphoid tissue (GALT) and bronchus associated lymphoid tissue (BALT). when the cortex layer looks light. Accidental transformation more often occurs in the newborn suffering from stress factors.45 of immune system. Information transmission is carried out through macrophage system. accidental involution consists of 5 stages.  The thymus produces and differentiates small lymphocytes (T-lymphocytes).  For identification of immunocompetent cells we use monoclonal antibodies to different immune cells. The density of the thymocytes is high. (2) B cell differentiation factor.e. B.  B-cells are defined as lymphocytes that bear membrane immunoglobulin and under appropriate conditions differentiate into antibody-secreting cells.  There are T and B-zones in the peripheral organs of the immune system. According to T. The more powerful is the stimulus. (7) interleukin-3. Among these cells are macrophages. The boundary between the layers is either poorly seen or not seen at all.lymphocytes and macrophages in the medullar substance. B. that is reduction in the size and mass due to thymocyte migration to the peripheral immune organs and blood as well as due to their partial" decomposition and absorption by macrophages (this is called apoptoses). 2. Stage 5 . Kupffer‟s cells of the liver. The function of B-cells is to produce antibodies.  Mononuclear Phagocyte is a general term applied to populations of phagocytic cells found in virtually all organs and connective tissues. (10) migration inhibition factor. and the so-called histiocytes. There are T-. in the children born from sick mothers. B-lymphocytes. paracortical zone and peripheral zone of the follicle is T-zone. In the lymphatic nodes. where they develop into more mature lymphoid cells. Gastrointestinal associated lymphoid tissue (GALT) and bronchus associated lymphoid tissue (BALT) have different immunocompetent cells.  The main T-cell function is to recognize “host” and “foreign” cells. If this condition is accompanied by .  Human Major Histocompatability Complex or human leukocyte antigens are the main target antigens during rejection of transplanted organs.lymphocytes and macrophages in the red pulp of the spleen. marginal zone is inhibited by Blymphocytes.collapse of the lobe of the thymus and sclerosis and lobe atrophy. At immunogenesis disturbances we usually see the following processes and pathology. Populations of bone marrow cells that may have recirculated back to the bone marrow can respond to antigens and are called B-lymphocytes. (4) fibroblast activating factor. thymomegaly). Microscopic examination reveals a large number of immature lobules (zones are not distinct). (5) Gamma-interferon. Thymus hyperplasia (thymolymphatic state. The process is reversible. T-lymphocytes.accumulation of lymphocytes around the macrophages. The main immunocompetent cells are T-lymphocytes. reticular stroma growth. Elimination of pathological agent results in thymus normalization.

liver. different stages of accidental transformation are observed. T-zone is characterized by “holey” appearance. as a result of increased transition of lymphocytes. as well as most types of glomerulonephritis. which develops rapidly.  Reticuloepithelium hyperplasia and lympho-plasmocyte infiltration occur in the interstitial tissue of the kidneys. Immunologically Mediated Tissue Injury. cell-mediated cytotoxisity also fall into this category. there are lymphocytes in the lumen. pancreas. Complement-independent reactions. 3. consequently attracting neutrophils and macrophages. An immune response that results in tissue injury is broadly reffered to as “hypersensitivity” reaction and is associated with a group of diseases categorized as immune and immunologically mediated disorders. T-zones and B-zone hyperplasia occurs. Type I Hypersensitivity (Immediate Type or Anaphylaxis) is manifested by a localized or generalized reaction that occurs immediately (within minutes) after exposure to an antigen to which the individual has previously become sensitized and is characterized by a specific cytotropic antibody that binds to receptors on basophils and mast cells and reacts with specific antigen. It includes: (1) delayed type hypersensitivity. Once deposited in the tissues. 3. Hypersensitivity is defined as a state of exaggerated immune response to an antigen. They represent the classic example of immune complex-mediated injury in which antigen-antibody complexes. Alteration manifests by mucoid.  In the bone marrow the first hyperplasia of B. poor development. After that both T and B-zones become empty. 1. Macrophages and plasmatic cells appear as well as their blasts producing immunoglobulins. are formed in the circulation and mainly directly in tissues.46 hypoplasia of adrenal and sexual glands as well as narrow aorta and arteries. appear to be mediated by type 111 hypersensitivity reactions. The lesions of hypersensitivity (immunologic tissue injury) are produced due to interaction between antigen and product of the immune response. Vascular endothelium is swollen. Lysis is mediated directly by complement or indirectly by opsonization or the chemotactic attraction of phagocytic cells. and muscles. As a rule thymus hypoplasia is typical for congenital immune deficiency. (2) T cell-mediated cytotoxisity. Type III Hypersensitivity reactions involve tissue injury mediated by immune complexes.with the release of potent inflammatory mediators. Type II Hypersensitivity (Cytotoxic Type) reactions are caused by an antigen-antibody reaction but. Type IV Hypersensitivity or Cell-Mediated Immunity is defined as an antigen-elicited cellular immune reaction that results in tissue damage and does not require the participation of antibodies. and proliferation increases slowly. 2. Complement is required for many of cytotoxic events. Many human diseases. and (3) natural killer cellmediated cytotoxisity. which are usually not organ-specifiic. The lymphocytes either die or circulate in the blood. when it becomes empty. two distinct forms of hypersensitivity reactions are recognized: Hypersensitivity of Immediate reaction morphologically manifests itself by the picture of acute immune inflammation. Sudden death syndrome (crib death) may occur in thymomegaly. alteration and exudation stages prevail. these complexes induce an inflammatory response by activating the complement system. as well as lymphocyte component. Changes of lymphoid tissue at antigen stimulation  In the thymus. the antibodies formed are often cytotoxic and are directed against antigens on cell surfaces or in connective tissues. is directly responsible for the injury. In B-zone density of the cells decreases. such as antibody-dependent. this pathological process is called “thymolymphatic state”. First.  The reaction in peripheral lymphoid organs is similar. intestines. Hypersensitivity reaction A state of balance in the immune responses (humoral or cell-mediated) is essential for protection against endogenous and exogenous antigens. it results from insufficiency of T-lymphocytes of the cortex and medullar substance of the adrenal glands. including anti-immune diseases such as systemic lupus erythematosus.lymphocytes are observed. of reticuloepithelial component. The exudate is either fibrinous or . Depending upon the rapidity and duration the immune response. 4. as the name implies. The vessels and connective tissues are involved first. This results in the activation of mast cells and basophils and the release of performed (granule) products as well as the synthesis of mediators. Activation of these cells by the immune complexes. responsible for hormonal function. Thymus hypoplasia is characterized by absence of lobule division into cortical and medullar substance. fibrinoid swelling and fibrinoid necrosis.

Microscopically.47 fibrino-hemorrhagic. glomerulonephritis.  Tolerance is best looked on as a diversion of the immune system to an active state of nonreactivity: that is. and combined T and B cell deficiencies.  An abnormal autoimmune response to self-antigens implies that there is a loss of immune tolerance. Hypersensitivity of Delayed reaction Two types of cells take part in this reaction. cellular (T cell). The defects are congenital or acquired and their precise etiologies are often unclear. 1. nodular periarteritis. Enzyme destruction of the transplant begins which is followed by its rejection.  The causes of autoimmune diseases are not clearly known. That is why HLA genes are included into predisposing factors in the pathogenesis of autoimmune diseases. T-lymphocyte suppressor activity). radiation and genetic factors may be responsible for them. Before studying the pathogenesis of autoimmune diseases it is necessary to know the major histocompatibility complex (MHC). Cellular infiltration causes the disturbance of blood circulation and edema. It is responsible for vascular reaction in lupus erythematosus. 2. genetically dependent features of the target cells). Immunodeficiency Diseases Immunodeficiency disorders are classified into antibody (B cell). There are a lot of autoimmune diseases.  Chronic viral infections. Combined T and B Cell Deficiencies 4. 2. which are connected. and granulomatosis.  Chronic mucocutaneous candidosis. Autoimmune diseases  Autoimmunity implies that an immune response has been generated against self-antigen (autoantigens).  Initiating (viral and bacterial infections. with genetic disturbances of HLA-Dr system. Transplant antigens induce the production of antibodies and sensibilized lymphocytes. Reaction of transplant rejection resembles delayed hypersensitivity reaction. They are sensibilized lymphocytes and macrophages. The main organ specific diseases are: . tuberculosis. Acquired Immunodeficiency. In many cases functional defects are localized to particular points in the ontogeny of the immune system. Acute immune inflammations are observed in tuberculosis. which infiltrate the transplant. The condition occurs in autoimmune diseases. Deficiencies of Antibody (B cell) immunity:  Congenital (Bruton’s) X-linked infantile hypogammaglobulinemia. Organospecific diseases. brucellosis. inhibitory products block the immune response. exposure of immune system and target organs to chemical and physical factors). Morphologically it manifests by chronic immune inflammation characterized by lymphocyte-macrophage infiltration. as a result degenerations and necrosis of transplant develop.and nonself-antigens. Deficiencies of Cell-Mediated (T Cell) Immunity:  DiGeorge syndrome. 3. They are characterized by disturbance of physiological isolation of the organs and tissues due to absence of immune tolerance.  Central to the concept of autoimmunity is the breakdown in the ability of the immune system to differentiate between self. The neutrophils and macrophages appear in the transplant. 3 markers. therefore all the autoimmune diseases can be divided into 2 groups: Group 1. hormonal background.  Selective IgA deficiency. syphilis.  Transient hypogammaglobulinemia of infancy. Lymphohistiocyte infiltration occurs in the tissues (like at slow hypersensitivity reaction). which includes class 1. 2 mechanisms can be distinguished.  In the pathogenesis. dermatitis.  Common variable immunodeficiency.  Contributing (dysfunction of immune system. lymphohistiocyte infiltration is observed in the transplant. When we see lymphocyte-macrophage infiltration accompanied by vascular plasmorrhagic and degenerative processes we can conclude about immune inflammation.  Class 2 MHC markers are also called HLA-Dr. In the pathogenesis of autoimmune diseases the following factors are distinguished:  Predisposing (HLA genes.

AIDS exhibits a spectrum of clinical manifestations. Organ non-specific diseases.insufficiency of cellular and humoral immunity (T. Goodpasture‟s syndrome. Group 2. It is observed in glomerulonephritis. e.g. weight loss.  Mixed connective tissue disease. in tumors.  Rheumatoid arthritis. acquired immune deficiencies. hepatitis. and lymphadenopathy. The diseases with autoimmune disturbances    In these diseases antigenic properties of the tissues change.T-cell deficiencies.  Primary IDS may be understood as primary defects in development of the immune system. a prodromal state manifested by fever. Except for the pathology of thymus and primary lymphatic tissue.  Scleroderma (Progressive systemic sclerosis). burn disease. Some of these are secondary to immunosuppressive therapy. and membranous glomerulonephritis.  Polyarteritis nodosa (PAN). Secondary ones results from diseases or drugs that affect immune system. T-cell deficiencies manifests by agenesis. All immune deficiencies are divided into 2 groups: primary or congenital immune deficiencies and secondary.  Alimentary tract: Autoimmune atrophic gastritis in pernicious anemia. ulcerative colitis. ect. The aquired immunodeficiency syndrome (AIDS) has become recognized as fatal and increasingly prevalent disease.  Polymyositis-Dermatomyositis. defects of development occur.  Primary IDS may be classified into following 4 general groups depending on the stage in development at which the defect occurs: . Immune deficiency syndromes   Immune deficiency syndromes result from immune system insufficiency. The major laboratory features of AIDS are lymphopenia and the loss of circulating T4 (helper/amplifier) lymphocytes. Autoimmunization is responsible not for the beginning but the progress of the disease as autoimmune antibodies appear during the disease.  Blood cells: Autoimmune hemolytic anemia. Graves' disease. e. autoimmune diseases. The type of inheritance is connected with X chromosome. hypoplasia of the thymus and T-dependent zones of the immune system. autoimmune thrombocytopenia. Gianzmann-Riniker syndrome (agammaglobulinemia of Swiss type). chronic active hepatitis. . e. rheumatism. e.B-cell). agammaglobulinemia – Bruton‟s syndrome. .g. MacCusic syndrome. This is inherited according to autosome-recessive type.  Others Myasthenia gravis: Autoimmune orchitis.48  Endocrine glands: Hashimoto‟s (autoimmune) thyroiditis.  Reiter‟s syndrome. . idiopathic Addison‟s disease.g. The etiologic agent of . They are inherited according to autosome dominant type.g. primary biliary cirrhosis. The thymus is preserved. B-cell deficiencies. Immunoglobulins synthesis is absent. Crohn‟s disease. Combined syndromes .  Autoimmune skin diseases. and the classic picture of opportunistic infections and Kaposi‟s sarcoma.  Sjogren‟s syndrome.B-cell deficiencies. including an asymptomatic state with only laboratory evidence of immunodeficiency.Deficiency in inflammatory cells (agranulocytosis). chronic gastritis. Hypoplasia of thymus and peripheral lymphatic tissue. autoimmune encephalomyelitis.Combined (T-B-cell) deficiencies. Chronic virus infections and HIV (human immunodeficiency virus) may cause secondary deficiencies. B-zones in the peripheral lymphatic organs are absent. insulindependent diabetes mellitus. which causes immune reaction development. glomerulonephritis. Secondary deficiencies occur after full development of the immune system. hepatic cirrhosis. Primary disturbances in the immune system causing the loss of ability to distinguish “own” and “foreign” antigens are:  Systemic lupus erythematous.

Macroscopic features. IV.  Malignant tumors are usually irregular in shape. fungati. 7. glands as well as epithelial integument (organspecific). 6. Tumors of nervous system and brain membranes. Sarcomas typically have fish-flesh like consistency while carcinomas are generally firm. hepatoma for carcinoma of the hepatocytes. Teratomas. texture and consistency as compared to the surrounding tissue of origin. while malignant mesenchymal tumors are named sarcomas (sarcos = fleshy).e. all “new growth” is not neoplasms since examples of new growth of tissues and cells also exist in the processes of embriogenesis. Gross terms such as papillary. Tumors composed of a single type of parenchymal cells that differentiate towards more than one cell line are called mixed tumors. uncoordinated. Growth rate. Local invasion (Direct spread). contrasting features of benign and malignant tumors are summarized in Table 6. their total number exceeds 200. According to this classification. 5.  Benign tumors are generally spherical or ovoid in shape. hyperplasia and hormonal stimulation. peculiarity of their structure in a definite organ. excessive. Malignant tumors of epithelial origin are called carcinomas. the new growth produced is called “neoplasm” or “tumor”. poorly-circumscribed and extend into the adjacent tissues. regeneration on repair. ulcerative and cystic are used to describe the macroscopic appearance of the tumors. Mesenchymal tumors. Macroscopic features  Almost all tumors have a different color. 1. Based on these characteristics.49 AIDS is now known to be a retrovirus originally called HTLV-111 (human T cell leukemia/lymphoma virus). more often firm and uniform. Metastasis (Distant spread). tissue of origin) and on the anticipated behavior.  However. V. infarction and ulceration are seen more often. Tumors of endocrine and exocrine. They are encapsulated or wellcircumscribed.  Neoplastic cells lose control and regulation of replication and form an abnormal mass of tissue. 4. Tumors of blood system. freely movable.  The tumors are classified according to histogenetic principles with the account of their morphological structure. The currently used classification of tumors is based on the histogenesis (i. lymphoma for malignant tumor of the lymphoid tissue. Tumors of melanin-forming tissue. unless secondary changes like hemorrhage or infarction supervene. Hamartoma is a mass of disorganised-but mature cells of tissues indigenous to the particular site. Teratomas. benign or malignant character. localization. The classification was suggested as an international one by the Committee on Tumor Nomenclature of the International Anticancer Union. autonomous and purposeless proliferation of cells”. III. and seminoma for malignant tumor of the testis. hemorrhagic. 3. . II. Choristoma refers to the ectopic rests of normal tissue. there are 7 groups of tumors. infiltrating. are made up of a number of parenchymal cell types arising from totipotent cells derived from more than one germ cell layer. Epithelial tumors without specific localization (nonorganspecific). Microscopic features. on the other hand. Characteristics of tumors The characteristics of tumors are described under: I. The suffix “-oma” is added to denote benign tumors. I.  Satisfactory definition of neoplasm or tumor is “a mass of tissue formed as a result of abnormal. 2. NEOPLASIA General pathomorphology of neoplasia  The term “neoplasia” means new growth. Secondary changes like hemorrhage. Some examples contrary to this concept are: melanoma for carcinoma of the melanocytes.

e. quadripolar and multipolar spindles in malignant tumour cells because increased number of normal mitoses may be present in non-neoplastic proliferations such as in hematopoietic cells of the bone marrow. The extent of cellular pleomorphism generally correlates with the degree of anaplasia.g. 2) Nucleocytoplasmic changes.  Characteristically. absence of keratin in anaplastic squamous cell carcinoma. large or small amount of collagen produced by benign tumors of fibrous tissue. As a result of anaplasia. are another important feature of anaplasia. and inflammatory reaction. referred to as hyperchromatism.  The nuclei too.  The epithelial tumors generally consist of acini. Microscopic features: These are: microscopic pattern. a prominent nucleolus or nucleoli may be present in these nuclei reflecting increased nucleoprotein synthesis. reticulin network in soft tissue sarcomas etc. qualitative. sheets. columns or cords of epithelial tumor cells that may be arranged in solid or papillary pattern. Besides.g. . “Poorly differentiated”.  Anaplasia is lack of differentiation and is a characteristic feature of most malignant tumors. 1. there is usually quantitative fall in the product made by the tumor cells. Structural anaplasia in tumors is accompanied with functional anaplasia. “undifferentiated” or “dedifferentiated” are synonymous terms for poor structural and functional resemblance to corresponding normal cell. intestinal epithelium. Most malignant tumors show aneuploidy.  The mesenchymal tumors have mesenchymal tumor cells lying separated from each other usually by the intercellular substance such as cartilaginous matrix in chondroma. Tumor Cytomorphology (Differentiation and Anaplasia)  Differentiation is defined as the extent of morphological and functional resemblance of parenchymal tumor cells to corresponding normal cells. e. following noticeable morphological and functional alterations in the neoplastic cells are observed: 1) Pleomorphism means variation in size and shape of the tumor cells.g.  Other cellular deviations from the normal cellular arrangement in malignant tumors are: loss of basal orientation (polarity). show variation in size (anisonucleosis) and shape in malignant tumor cells.  Hematopoetic tumors such as leukemias and lymphomas often have none or little stromal support. But the more anaplastic tumor cells lose such features. 3) Genetic abnormalities. osteoid in osteosarcoma. the tumor is described as “well-differentiated” such as most benign and low-grade malignant tumors. though there may be quantitative abnormality in the product. Microscopic patten: The tumor cells may be arranged in a variety of patterns in tumors. angiogenesis and tumor stroma. The functional abnormality in neoplasms may be quantitative. cytomorphology of neoplastic cell (differentiation and anaplasia). altered alignment of tumor cells to each other. most benign tumors and low-grade malignant tumors reduplicate the normal structure of origin more closely. e. so that the nucleocytoplasmic ratio is increased. the nuclei of malignant tumor cells are enlarged.  Multinucleate tumor giant cells or giant cells containing a single large and bizarre nucleus. In more anaplastic tumors. possessing nuclear characters of the adjacent tumor cells. These are as under:  Generally. All tumor cells have abnormal genetic composition and on division they transmit the genetic abnormality to their progeny. and stromal invasion by tumor cells.  Generally. or both.  The cytoplasm of tumor cells in better-differentiated cancers and in benign tumors may show the normal constituents from which the tumor is derived. benign tumors and better-differentiated malignant tumors continue to function well qualitatively. keratin formation in well-differentiated squamous cell carcinoma. 4) Functional changes.50 II. the nuclear chromatin of malignant cell is increased and coarsely clumped. 2. hepatocytes etc. Generally.  It is most important to identify abnormal and atypical mitotic figures such as tripolar. If the deviation of neoplastic cell in structure and function is minimal as compared to normal cell.

if the tumor outgrows its blood supply as occurs in rapidly growing tumors. some tumors show chronic inflammatory reaction. Cytoplasm May be present but are always typical mitoses May be present but without nuclear atypia May show normal constituents 10. 3. it is called medullary. it is referred to as desmoplasia and the tumor is hard or scirrhous. chiefly of lymphocytes. due to cell-mediated immunologic response by the host in an attempt to destroy the tumor. If the tumor is almost entirely composed of parenchymal cells.g. Pattern 8. Inflammatory Reaction. malignant melanoma of the skin. Warthin‟s tumor of salivary glands etc. Function Usually well maintained MACROSCOPIC FEATURES 1. The connective tissue along with its blood supply forms the supportive framework on which the parenchymal tumor cells grow and receive nourishment. and in some instances. new blood vessels are formed from pre-existing ones (angiogenesis) that is probably stimulated by secretion of tumor angiogenesis factors from the parenchymal tumor cells such as vascular endothelial growth factor (VEGF). its core undergoes ischemic necrosis. Hyperchromatism Normal Increased Absent Absent Generally present Often present 7. granulomatous reaction.g. lost or become abnormal . plasma cells and macrophages. seminoma testis. However. In order to provide nourishment to growing tumor. e. Angiogenesis and Tumor Stroma. e. FEATURES BENIGN (DIFFERENTIATED) MALIGNANT (UNDIFFERENTIATED) Poorly-circumscribed and irregular 2. 4. prominent inflammatory reaction is present in and around the tumors. MICROSCOPIC FEATURES 1. However. called ectopic hormone production. At times. Tumor giant cells Usually invaded Often lost Normal cytopiasmic elements are reduced or lost May be retained. Pleomorphism Usually not present Often present 4. Secondary changes Usually small Occur less often Often larger Occur more often Often poor resemblance to tissue of origin 2. lymphoepithelioma of the throat. Basal polarity Usually resembles the tissue of origin closely Retained 3. Size 4. It could be the result of ulceration in the cancer when there is secondary infection. Mitoses Mitotic figures increased and are generally atypical and abnormal Present with nuclear atypia 9. oat cell carcinoma of the lung can secrete ACTH and ADH. medullary carcinoma of the breast. Surrounding tissue Encapsulated or wellcircumscribed Often compressed 3. TABLE 6: Contrasting Features of Benign and Malignant Tumors. Boundaries II. Nucleo-cyto-plasmic ratio 5. Anisonucleosis 6.51 Hormones or hormone-like substances may be produced by certain tumors quite unrelated to the endocrine glands. if there is excessive connective tissue stroma.

Malignant tumors also enlarge by expansion. In general.52 III. 2. infiltrating (invasive).  Exophytic growth is expansive growth of the tumor to the cavity of the organ. the tumors invade thin-walled capillaries and veins than thick-walled arteries. blood vessels. possibly due to necrosis caused by good host immune attack. LOCAL INVASION Often compresses the surrounding tissues without invading or infiltrating them Absent Usually infiltrates and invades the adjacent tissues V. In relation to the lumen of the hollow organ. Rate of division and destruction of tumor cells. the whole lymph node may be replaced and enlarged by the metastatic tumor. Rarely. there are different types of its growth: expansive. These are the connective tissue stroma. benign tumors grow slowly and malignant tumors rapidly. can metastasize. The regulation of tumor growth is under the control of growth factors secreted by the tumor cells. Growth rate The tumor cells generally proliferate more rapidly than the normal cells. abundant mucoid material. IV. they are distinguished from benign tumors by invasion. apposition. of course. More commonly. and perineural spaces and may penetrate a bone by growing through nutrient foramina. The tumor emboli enter the lymph node at its convex surface and are lodged in the subcapsular sinus. V. besides distant metastasis. infiltrating or metastasising.  Endophytic growth is infiltrating growth of the tumor deep into the wall of the organ. and is characteristic benign tumors. Metastasis is the most important feature to distinguish malignant from benign tumors. 3. carcinomas metastasize by lymphatic route while sarcomas favour hematogenous route. Sometimes lymphatic metastases do not develop first in the lymph node nearest to . they can be unicenter (one focus) and multicenter (several foci). In general. the growth of the tumor may be endophytic or exophytic.proportion of cells undergoing mitosis (milotic index). Routes of metastasis: 1. 1.  At expansive growth the tumor grows from itself moving away the surrounding tissues. a malignant tumor such as choriocarcinoma and malignant melanoma may disappear spontaneously from the primary site. only to reappear as secondaries elsewhere in the body. Often. According to the number of foci of tumor development. cancers extend through tissue spaces. Metastasis (distant spread) Metastasis is defined as spread of tumor by invasion in such a way that discontinuous secondary tumor mass/masses are formed at the site of lodgement. But. cartilaginous matrix etc all of which add to the bulk of the tumors. spread via cerebrospinal fluid. Hematogenous spread. Lymphatic spread. This type of growth is slow. METASTASIS Frequently present III. infiltration and destruction of the surrounding tissue. implantation). The rate at which the tumor enlarges depends upon 3 main factors: 1. 3.  Apposition growth is due to transformation of normal cells to tumor ones. GROWTH RATE Usually slow Usually rapid IV. The walls of lymphatics are readily invaded by cancer cells and may form a continuous growth in the lymphatic channels called lymphatic permeation. Benign tumors do not metastasize while all the malignant tumors with a few exceptions like gliomas of the central nervous system and basal cell carcinoma of the skin. Non-neoplastic elements within the tumors. Lymphatic spread.  In infiltrating growth the cells of the tumor invade normal tissues and destroy them (so called destructive growth). 2. Later. Degree of differentiation. rate of growth of malignant tumor is directly proportionate to the degree of differentiation. The rate of division of tumor cells depends upon 2 factors . Other routes (spread along epithelium-lined surfaces. and the duration taken to complete the mitotic cell cycle. In general. permeate lymphatics. Local invasion (direct spread) Most benign tumors form encapsulated or circumscribed masses that push aside the surrounding normal tissues without actually invading. Depending on the degree of the tumor differentiation. or may detach to form tumour emboli.

1. 4. etc. all of which provide “good soil” for the growth of “good seeds” (seed-soil theory) than are the unfavourable sites like the spleen and muscles.g.Virus. Chemical carcinogens. 1. 2. Carcinogens are a variety of extrinsic agents. Local effects. Biologic carcinogens (chiefly viruses). physical. ulceration. that encompasses exogenous agents like chemical. e.). the lymph flow is disturbed and retrograde metastases may be seen at unusual sites. chemical. i. dyshormonal. 3. Tissue destruction. Hormonal carcinogens. 2. so called carcinogens. Some of the local effects of tumors are as under     Compression. together referred to as cancer cachexia. Dysontogenetic theory was created by J. physical. Effect of tumor on host Malignant tumors produce more ill effects than the benign tumors. Oncogenic viruses are those containing DNA and RNA (Epstein-barr virus. It states integration of the genomes of the virus and the normal cell that is combination of nucleic acid of the virus with genetic apparatus of the cell. breast. II. hormonal and biological substances. Both benign and malignant tumors cause local effects on the host due to their size or location. lungs. kidney and prostate. Physical carcinogens (mainly radiation). Infarction. Fever. Hematogenous spread. so called stop metastasis. Carcinogenesis Carcinogenesis means inductions of tumors. hepatitis B. The exact mechanism of tumor-associated fever is not known but probably the tumor cells themselves elaborate . Fever of unexplained origin may be presenting feature in some malignancies such as in Hodgkin‟s disease. parasite. tumors appear from embryonic tissue and abnormally developed tissues under the influence of different causative agents. Carcinogenesis. The common sites for blood-borne metastasis are the liver. which can induce tumors. thyroid. Predisposing epidemiologic factors. 2. venules and veins than the arteries which are thick-walled and contain elastic tissue resistant to invasion. Etiology and pathogenesis of neoplasia The etiology of tumors is various. Mechanical obstruction. are called carcinogens. 4. which include a number of endogenous host factors and exogenous environmental factors. metastatic deposits in the adrenals from carcinoma lung etc. hemorrhage. Other times. viral.e. kidneys. Clinical aspects of neoplasia Two major aspects of clinical significance in assessing the course and management of neoplasia are tumor-host inter-relationship and laboratory diagnosis of cancer. Cancer cachexia. Metastasis through blood vessels is the common route for sarcomas but certain carcinomas also frequently metastasize by this mode. osteogenic sarcoma and many other tumors. Polyetiological theory emphasizes the importance of different factors. According to his theory. herpes virus.53 the tumor because of venous-lymphatic anastomoses or due to obliteration of lymphatics by inflammation or radiation. metastasis of carcinoma prostate or stomach to the supraclavicular lymph nodes. agents. 4 theories are recognized. and anorexia. 3. Cancers of the organs draining into portal veins frequently establish metastasis in the liver. adenocarcinoma kidney. Based on the current state of knowledge. due to obstruction of the lymphatics by tumor cells. which are broadly divided into 4 groups: 1. brain and bones. Physicochemical theory suggests that tumor appears under the influence of different physical and chemical substances. Virogenetic theory. Cohnheim. these factors are broadly described under 2 main headings: I. which turns into tumor ceil. The cancer cells readily invade the walls of capillaries. especially those of the lung. while cancers of organs draining into caval veins metastasize to the lungs. Patients with advanced and disseminated cancers terminally have asthenia (emaciation). 2. 3.

etc.  Adenomas have atypical structure. 5. prostatic gland. immunohistochemistry.insulin. medullar layer of adrenal gland .  Origin from the skin and mucous membranes. These cyst-like adenomas are called cystoadenomas.  Adenomas from compact organs (liver.  Sometimes epithelial growth is so intensive that the papillae invade the walls of flie cyst. histochemistry and cytochemistry. their thin branching papillae can be easily injured and bleed. Malignant epithelial tumors . beta cells of pancreas . involve the peritoneum.  Soft papillomas consist of thin fibers with thin-walled vessels. The most certain and reliable method which has stood the test of time is the histological examination of biopsy. These papillomas are mainly found in the neck of the urinary bladder and in the region of the triangle. thyroid gland. formation of mucus. from chemo*-or radiotherapy.  In some adenomas glandular cavities are widened and form large cavities. inflammation.somatotropic hormone.noradrenaline.  Slow growth. relapse.g. hematologic. adenomas of mucous membranes . They manifest by foci of necrosis. parenchyma and stroma ratio (fibroadenoma. numerous bubbles bedded with cylindrical or cubic epithelium are observed in the connective tissue with vessels. adenofibroma) in the glandular tubules and vesicles. liver. gastrointestinal tract. gastrointestinal.  The base of the tumor consists of connective tissue containing blood vessels.  Exophytic tumor. which are not explained by direct and distant spread of the tumor (endocrine. pharynx). They grow quickly. thyroid gland. They develop in ovaries. the structure of adenomas is similar to that of the original organ. larynx. there are glandular cavities resembling tubes in the connective tissue with vessels.  More often they can be found in the breast.54 pyrogens. They often become malignant turning into cancer. Adenoma  Benign epithelial tumor from the epithelium of the glands and glandular organs. Secondary changes in the tumor result from disturbances of blood circulation. amyloidosis).  Hard papillomas locate on the skin and mucous membranes covered with multilayer squamous epithelium (mouth. Papilloma has following features  Bening tumor.  May be hard of soft. calcification. hemorrhages. which is the cause of their functional similarity (ability of adenoma cells to produce respective secretes) e. tumors of glandular epithelium (adenomas). produce metastases. neuromuscular. They are covered with cylindrical transition or ciliated epithelium.  In alveolar adenoma. adenomas of eosinophilic cell of the anterior lobe of pituitary . size and location. which manifests in absence of ducts. cysts filled with serous fluid or mucus.mucus.  Thus. Paraneoplastic syndromes. cytological methods.  It looks like a ledge or a bush of branching papillae. renal syndromes.  In tubular adenoma. EPITHELIAL TUMORS Benign epithelial tumors Benign epithelial tumors are subdivided according to their origin from different types of epithelium into the tumors of integumentary epithelium (papillomas). cause cachexia and may cause sever consequences. ovaries. These adenomas are termed papillary adenocystomas. Paraneoplastic syndromes (PNS) are a group of conditions developing in patients with advanced cancer.  It is a continuation of subepithelial connective tissue covered with epithelium like. Adenocystomas may become malignant more frequently than the other adenomas.  According to the histological composition adenoma may be tubular and alveolar. adrenal gland) can be made of groups of respective cells separated from each other by a thin layer of stroma. 4. Diagnosis of cancer. variety of shape.

Usually they have the structure of capillaries. its development is preceded by different processes characterized by: 1) prolonged chronic course. adenocarcinoma (trabecular. Early gastric carcinoma. hypernephroid cancer). 3. commonly papillary type. 3) Special kinds: chorionepithelioma. chorionepithelioma. The men at the age of 40-60 suffer more often than women. The second common pattern is a cauliflower growth projecting into the lumen. vessels in tumors are new structures but they are connected with general circulation. According to it all cancers can be divided into 3 groups: 1) Poorly-differentiated: small-cell or large-cell. 2) Fungating (polypoid) carcinoma. displasia). malignant tumors are characterized by infiltrating tumor growth. Together with tissue and cellular atypism. Early gastric carcinoma must be distinguished from certain related terms: epithelial dysplasia (cellular atypia seen in intestinal metaplasia such as in atrophic gastritis and pernicious anemia). scirrhus. 3) Scirrhous carcinoma. infiltrating and ulcerative growth with irregular necrotic base and raised margin. The term came to us from the time of Hippocrates and Galen. It is seen more commonly in the region of gastric canal. This is the most common pattern. Classification: According to the deepness of the lesion in the gastric wall there are 2 types of carcinoma: 1. Advanced gastric carcinoma has following patterns: 1) Ulcerative carcinoma. disturbed tissue regeneration (abundant granulation. does not appear at once. medullar.. when carcinoma confined only mucosa layers. Blood vessels in the tumors look differently. If both stroma and parenchyma of the tumor are anaplastic. similar to what is commonly seen in the large intestine. and leukoplakias of the mucous membrane. when it penetrates the muscular layer or beyond. papillary. The lumen of the stomach is reduced. it is important to know that invasion of the tumor cells in the veins is difficult because they become narrowed. Microscopically. The tumors may be connected with the sources of nutrition in different ways. alveolar.  Pre-cancer changes in the gastric mucosa: 1. Clinical-anatomical practice suggests that tumor. cardia and fundus.  Gastric carcinoma is most commonly located in the region of gastric canal (prepyloric region). which invade deeply into the stomach wall. When the carcinoma crosses the basement membrane into the muscular propria or beyond. The morphological classification is based on differentiation of the tumor cells. seminoma. It is seen more often in the fundus. seminoma. chronic inflammatory diseases. termed sarcocarcinomas or carcinosarcomas. polyposis of mucous membrane. metaplasia. hypernephroid cancer. Chronic gastric ulcer. 2. the stomach wall is thickened due to extensive desmoplasia giving the appearance as “leather bottle stomach” or “linitis plastica”. The tumor undergoes necrosis and infection commonly. 3) failure of conservative treatment. As to metastases. ulcerative carcinomas are poorly-differentiated adenocarcinomas. or diffuse affecting whole of the stomach from the cardia to pylorus. it is referred to as advanced gastric carcinoma. There are no ulcers but rugae are prominent. solid. The tumour appears as a flat. The more directly they contact. Adenomatous polyps. without keratinization. 2) Well-differentiated: squamous-cell. In this pattern. including lost embryonic germs. 2. Tubular and acinar patterns are seen more commonly. Precancerous states: defects of development. the more rapidly it produces metastases (e. the more intensive is the growth of the tumor. chronic ulcers. tumors of epithelium are also called carcinoma. fungating or polypoid carcinomas are welldifferentiated adenocarcinomas. carcinoma in situ in the stomach (a state of severe cellular atypia or dysplasia. they characterize combination tumors. less common localization are the body. Microscopically.g. 2) association with cell multiplying. THE MOST OFTEN TUMORS Gastric carcinoma  Gastric carcinoma comprises more than 90% of all gastric malignant tumors. Advanced gastric carcinoma. as a rule. without invasion across the basement membrane of the glands). The involvement may be localized to pyloric antrum.55 Immature. hormonal hyperplasias. Macroscopically. mucous. with keratinization. As a rule. Atrophic gastritis. it may be an adenocarcinoma or . or malignant.

around the cardial and suprapancreatic lymphnodes. brain. they are carried through the lymphatic vessels to regional lymphatic nodes . 5) Ulcer-cancer. Metastases can be: 1. According to the macroscopical signs pulmonory carcinoma may be:  Superficial spreading type.  Branching type.  Small cell carcinoma.  Solid carcinoma.  Bronchiole-alveolar carcinoma. intermediate cell type.  Fundal gastric carcinoma (2%). Majority of ulcer-cancers are malignant lesions from the beginning. This pattern is usually seen in the fundus. the characteristic microscopic appearance of peptic ulcer should be demonstrable with one portion of the base or the margin of the ulcer showing carcinomatous changes.  Nodular-branching type. Carcinoma of lungs According to the types of growth pulmonary carcinoma may be: Exophytic (endobronchial) type.  Endobronchial diffusely spreading type. 2. 4) Colloid (mucoid) carcinoma. trabecular (well. 2. kidneys and adrenal glands. bones. lungs.  Nodular type.differentiated).  In orthograde metastases.  Signet-ring cell carcinoma. Squamous-cell carcinoma. ulcer-cancers are adenocarcinomas without any specific features. but due to marked desmoplasia cancer ceils may be difficult to find.  Adenosquamous carcinoma. extensively infiltrating the stomach wall.   . Microscopically. sometimes having signet-ring appearance. when the carcinoma disseminates through the peritoneum or penetrates to the pancreatic glands.56 signel-nng cell carcinoma. Implantation (contact).  In retrograde metastases they are carried through the lymphatic vessels to the left supraclavicular lymphnode (Virchow’s gland). ovaries (Krukenberg tumor). Lymphogenic. Endophytic (exobronchial and peribronchial) type. scirrhous carcinoma. According to the location gastric carcinoma may be:  Pyloric (50%) gastric carcinoma. 3.  Total gastric carcinoma (3%).  Greater curvature of the stomach (3%). mucoid.  Papillary carcinoma.along the lesser and greater curvature. Hematogenic metastases are carried with the blood flow to the liver. pararectal tissue (Shnitsler’s metastases). solid carcinoma (poorly-differentiated). For confirmation of cancer in a pre-existing gastric ulcer. According to the histoiogical signs there are the following types of gastric carcinoma:  Adenocarcinoma: papillary.  Polypoid type. Small cell carcinoma:  Oat cell carcinoma. mucoid carcinoma contains abundant pools of mucin in which are seen a small number of tumor cells.  Combined oat-cell carcinoma.  Lesser curvature of the stomach (27%). There are 2 types of them: orthograde (with the lymph flow) and retrograde (against the lymph flow).  Cardial gastric carcinoma (15%).  Squamous-cell carcinoma. According to the histological types the bronchogenic carcinoma may be: 1. The tumour grows like masses having gelatinous appearance due to secretion of large quantities of mucus. 3. Adenocarcinoma:  Acinar carcinoma. Microscopically.

inconspicuous nucleoli and very sparse cytbplasm. Hilar type has following features:  Etiopathogenesis: smoking. tubules or papillae but having mucus-containing vacuoles in many tumor cells. Solid carcinoma is a poorly-differentiated adenocarcinoma lacking acini. 2.  The lung cancer arises in the main bronchus or one of its segmental branches in the hilar parts of the lung. 1 to 5 cm in diameter.  Usually the spread of squamous cell carcinoma is more rapid than the other histologic types. have strong relationship to cigarette smoking and are highly malignant tumors.  The cut surface of the tumour is yellowish-white with foci of necrosis and hemorrhages which may produce cavitary lesions. Adenocarcinoma of lungs. genetic factors.  The tumor is diagnosed microscopically by identification of either intercellular bridges or keratinization. Adenocarcinoma is further subclassified into 4 types: 1. and to distant sites by lymphatic or hematogenous routes. 3. round or oval nuclei having diffuse chromatin.Papillary adenocarcinoma. Adenosquamous carcinoma. chronic scarring. Small cell carcinomas are frequently hilar or central in location. abscess formation and bronchiectasis as a result of obstruction and accompanying infections. it thickens the bronchial mucosa producing nodular or ulcerated surface.  The tumor soon spreads within the lungs by direct extension or by lymphatics.  Nodular carcinoma grows into a friable spherical mass. the edge of the growth and the adjoining uninvolved bronchi show squamous metaplasia.  It is common to find secondary changes in the lungs such as bronchopneumonia. Peripheral type:  A small proportion of lung cancers. Small cell carcinomas may be:  Oat-cell carcinoma is composed of uniform.  More often on the right side. narrowing and occluding the lumen. which has a pronounced papillary configuration and is frequently peripherally located in the lungs and is found in relation to pulmonary scars (scar carcinoma). which has predominance of glandular structure and often occurs in the larger bronchi.  Frequently. occupational causes. epithelial dysplasia and carcinoma in situ.  The tumor may be a single nodule or multiple nodules in the periphery of the lung producing pneumonia-like consolidation of a large part of the lung.  The tumor begins as a small roughened area on the bronchial mucosa at the bifurcation. 5. dietary factors. Large cell carcinoma.  As the tumor enlarges. These cells are organized into cords. . dense. Adenocarcinoma is the most common bronchogenic carcinoma in women and is slowgrowing. chiefly adenocarcinomas including bronchioloalveolar carcinomas. small cells. Squamous cell (epidermoid) carcinoma  These tumors usually arise in a large bronchus and are prone to massive necrosis and cavitation. Acinar adenocarcinoma. Bronchiole-alveolar carcinoma is characterized by cuboidal to tall columnar and mucus-secreting epithelial cells growing along the existing alveoli and forming numerous papillary structures. atmospheric pollution.  The cut surface of the tumor is grayish and mucoid. Small cell carcinomas.57 4. aggregates and ribbons or around small blood vessels forming pseudorosettes.  It originates from a small peripheral bronchiole but the exact site of origin may not be discernible. larger than lymphocytes with. 4. They are most often associated with ectopic hormone production because of the presence of neurosecretory granules in majority of tumour cells which are similar to those found in argentaffm or Kulchitsky cells normally found in bronchial epithelium. According to its location bronchogenic carcinoma may be hilar and peripheral.

. According to the WHO.5-5. papillary and cribriform. In situ lobular carcinoma is characterized by filling up of terminal ducts and ductules or acini by rather uniform cells. Large cell carcinoma. 2.  On cut section. which lack a fibrovascular stalk so as to distinguish it from intraductal papilloma. pancreas. c) Papillary type has formation of intraductal papillary projection of tumor cells. intermediate cell type is composed of cells slightly larger than those of oat cell carcinoma and have similar nuclear characteristics but have more abundant cytoplasm.  Large cell carcinomas are more common in men. brain.through the lymphatic vessels to regional lymphatic nodes -hilar. 3. adrenal and thyroid glands.58  Small cell carcinoma.  Macroscopically. Carcinoma-in situ confined within the larger mammary ducts is called intraductal carcinoma. These cells are organized into lobules. the tumor may vary from a small poorly-defined focus to 2. b) Comedo type is centrally placed necrotic debris surrounded by neoplastic cells in the duct. Two types of carcinoma in situ are described: intraductal carcinoma and lobular carcinoma in situ. 1. Breast cancer There are cancer of ducts. Hematogenic metastases are carried with the blood flow to the liver. kidneys. the proliferating tumour cells within the ductal lumina may have 4 types of patterns in different combinations: solid. Non-invasive (in situ) carcinoma The tumour cells within the ducts or lobules without evidence of invasion. have strong association with cigarette smoking and are highly malignant tumors. which lack the specific features by which they could be assigned into squamous cell carcinoma or adenocarcinoma. Lobular carcinoma in situ is identified only microscopically.  Combined oat-cell carcinoma is a tumour in which there is a definite component of oat cell carcinoma with squamous cell and/or adenocarcinoma. Invasive carcinoma 1. Implantation (contact) when the carcinoma disseminates through the pleura or penetrates to the peribronchial lung tissue. Secondary complications: hemorrhages. which are loosely cohesive and have small.  The tumor cells have large nuclei. cervical. comedo. prominent nucleoli. abundant cytbplasm and welldefined cell borders. rounded nuclei with indistinct cytoplasmic margins. They may occur: a) Solid type is characterized by filling and plugging of the ductal lumina with tumorous cells. supraclavicular and paraaortic lymphnodes. 2.5 cm diameter mass. d) Cribriform type is recognized by neat punched out fenestrations in the intraductal tumor.  These are undifferentiated carcinomas. bones. carcinoma of the breast is subdivided on 2 main types non-invasive carcinoma and invasive one. Infiltrating ductal (not otherwise specified) is the classic breast cancer. or the intraductal tumour may be polypoid and friable resembling intraductal papilloma (papillary pattern). necrosis of the tumor as well as cachexia. These are a small proportion of peripheral scar carcinomas having clear evidence of both keratinisation and glandular differentiation. Lymphogenic . Morphological features are:  The tumor initially begins with atypical hyperplasia of ductal epithelium followed by filling of the duct with tumour cells. nipple and areola. mediastinal. tumor shows cystically dilated ducts containing cheesy necrotic material (comedo pattern). parenchyma.  Micrpscopically. Adenosquamous carcinoma. Metastases can be: 1.

parasternal nodes.  Microscopically. the tumor is different from other special types in lacking a regular and uniform pattern throughout the lesion.individual tumor cells resemble cells of in situ lobula of carcinoma. Tumors cervix and body uterus . axilla. the underlying breast contains invasive or non-invasive duct carcinoma.20 years after the operation. Infiltrating (invasive) tubular carcinoma. cords. the former to the lymphatic nodes of the breast base. b) Infiltration by these patterns of tumor cells into diffuse fibrous stroma and fat. and liver. Paget‟s cells are adenocarcinoma-type cells. are seen floating iti large lakes of mucin.  Microscopically. as the name NOS suggests. There are 3 histological types of this carcinoma: a) Anaplastic tumor cells forming solid nests. it may have multicentric origin.50% to the bones. invasive cancers in being more frequently bilateral and within the same breast. In addition. Distant metastases are hematogenic ones. which shows no obvious direct invasion of the skin of nipple. well-circumscribed.  The sectioned surface of the tumor is gray-white to yellowish with chalky streaks and often extends irregularly into the surrounding fat. the skin of the nipple and areola is crusted. the tumour is characterized by a large.59  Macroscopically. subclavicutar. Medullary carcinoma has a significantly better prognosis than the usual infiltrating duct carcinoma. 4. the skin lesion is characterized the presence of Paget‟s cells singly or in small clusters in the epidermis. Microscopically. the appearance varies from a well-defined scirrhous mass to a poorlydefined area of induration that may remain undetected by inspection as well as palpation.  Macroscopically. Cuboidal to tall columnar tumour cellsi some showing mucus vacuolation. They are round and regular with very little pleomorphism and infrequent mitoses. Colloid (mucinous) carcinoma contains large amount of extracellular epithelial mucin and acini filled with mucin. b) The loose connective tissue stroma is scanty and usually has a prominent lymphoid infiltrate. Some tumors may show signet-ring cells distended with cytoplasmic mucus. The metastases are either local or distant. c) Invasion into perivascular and perineural spaces as well as lymphatic and vascular invasion. large vesicular nuclei and many bizarre and atypical mitoses are diffusely spread in the scanty stroma. spherical. poorly-formed glandular structures and some intraductal foci.a characteristic single file (Indian file) linear-arrangement of stromal infiltration by the tumor cells with very little tendency to gland formation is seen. 40 . b) Tumor cytology . scaly eczematoid lesion with a palpable subareolar mass in about half the cases. 2. 3.”  Cut section shows areas of hemorrhages and necrosis. Late metastases and relapses occur 5 . Paget’s disease of the nipple      The nipple bears a crusted. there are 2 characteristics: a) Pattern . hard cartilage-like mass that cuts with grating sound. Macroscopically. fissured and ulcerated. Infiltrating ceils may be arranged concentrically around ducts in a target-like pattern. 1-5 cm in diameter. In these respects. These cells are larger than the epidermal cells. lungs. having hyperchromatic nuclei with eytoplasmic halo that stains positively with mucicarmine.  There arc 2 histological characteristics of this tumor: a) Pleomorphic tumor cells with abundant cytoplasm.  Macroscopically. rounded mass that is typically soft and fleshy brain-like and hence the alternative name of “encephaloid carcinoma. probably due to good host immune response in the form of lymphoid infiltrate in the tumour stroma. the tumor is irregular.

mostly of the cystic variety. 5. Carcinoma extends beyond the cervix but not onto the pelvic wall. Cervical cancer is staged as follows: 1. Carcinoma of endometrium    The uterine corpus including its endometrium and myometrium is affected by a great variety of neoplastic growth. With current methods of treatment. The endometrial stroma (stromal nodule and stromal sarcoma). 4. This stage obviously includes those with metastatic dissemination.    There are sessile masses of variable size that project into the endometrial cavity. Histologically. there is % year survival rate about 80 to 90% with stage 1. 75% with stage 2. Eventually dissemination to the regional lymph nodes occurs. Squamous cell carcinoma may occur in any age from the second decade of life to senility. 2. Functional endometrium. 3. Carcinoma confined to the cervix: preclinical carcinoma diagnosed only microscopically but showing. 2. but not to the lower third. Endomterial polyps are bening tumors. Carcinoma involves the vagina. adenocarcinomas may arise within endometrial polyps. Histologically. two general groups of endometrium cancer can be identified. Rarely. the tumor may be hematogenously borne to the lungs. most endometrial carcinoma is adenocarcinomas characterized by more or less well-differentiated gland patterns lined by malignant stratified columnar epithelial cells. 3. The most common of these tumors are the endometrial polyps. and endometrial carcinomas. In terms of potential pathogenesis. The peak incidence is in the 55 to 65-year-old women. and infiltrative cancer. These can be benign or malignant and can arise from 1. More commonly hyperplastic endometrium. The smooth muscle of the myometrium (leiomyoma. Carcinoma in situ. endometrial carcinoma presents as a localized polypoid tumor or as a diffuse tumor involving the entire endometrial surface. Carcinoma of endometrium        Carcinoma of endometrium is the most common invasive cancer of the female genital tract. Ten to twenty-five per cent of cervical carcinoma constitutes adenocarcinoma. The endometrium glands (endometrial polyps and endometrial carcinomas). adenosquamous arcinoma and undifferentiated carcinoma. 2. Invasive cervical carcinoma manifests in three somewhat distinctive patterns: fungating (or exophytic). bones and other organs. . leiomyosarcoma). Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. 4. The tumor involves the lower third of the vagina. It is uncommon in women younger than 40 years of age. The first and the most well-studied develops on a background of prolonged estrogen stimulation and endometrial hyperplasia. Histologically.60        Cervix is both a sentinel for potentially serious upper genital tract infections and a target for viral or chemical cancerogens. Carcinoma has extended onto the pelvic wall. Mixed mesodermal tumors. 35% with stage 3 and 10 to 15% with stage 4 disease. leiomyomas. Grossly. asymptomatic or may cause abnormal bleeding if the ulcerate or undergo necrosis. about 95% of squamous cell carcinomas are composed of relatively large cells either keratinizing (well-differentiated) or non-keratinizing (moderately differentiated) patterns. which may lead to invasive carcinoma. The more well-differentiated tumors tend to be those of endometrial differentiation. and in the late stages. made up of 1. they are generally of two types. They may be single or multiple. ulcerating.

epithelium-lined channels or ducts separated by a scant-to-abundant connective tissue stroma and sharply demarcated from the surrounding liver. Carcinoma of prostate gland Cancer of the prostate is the second most common form of cancer in males. and kidneys.  Microscopically. It is a disease of men above the age of 50 years and its prevalence increases with increasing age so that 60% or more of men 80 years old have asymptomatic carcinoma of the prostate. 2. Incidental carcinoma. Morphology  Macroscopically. permeating .  Hematogenous: pelvis. The malignant prostate is firm and fibrous. Hepatocellular carcinoma may appear macroscopically as a unifocal (usually large) mass. Liver cell adenomas are pale. multifocal. This is found unexpectedly as a small focus of carcinoma in the prostate during autopsy studies in men dying of other causes. and usually single discrete nodules rarely more than I cm in diameter. Portal tracts are absent. Latent carcinoma. but it may be deficient in places or entirely absent. squamous cell carcinoma and undifferentiated carcinoma.  They may reach 30 cm in diameter.  Administration of estrogens. followed in frequency by lung cancer. Occult carcinoma. This is the type in which the patient has no symptoms of prostatic carcinoma but shows evidence of metastases on clinical examination and investigations. in contrast to the liver cell adenoma.  Microscopically they are composed of uniformly sized.  Racial and geographic influences (in Americans). Its incidence in autopsies has been variously reported as 25-35%. instead prominent arterial vessels and draining veins are distributed through the substance of the tumor. About 15-20% of prostatectomies done. pale. Liver tumors Benign tumors 1. and frequently bile-stained nodules.  In patients with Klinefelter’s syndrome. transitional cell carcinoma. especially in the posterior lobe. or a diffusely infiltrative cancer. Cut section is homogeneous and contains irregular yellowish areas. prostatic carcinoma is located in the peripheral zone. found anywhere in the hepatic substance but often beneath the capsule. lungs. widely distributed nodules of variable size. Metastases:  Lymphogenous: sacral. they are almost never bile stained. adenoacantoma) when associated with well-differentiated adenocarcinomas. two histologic patterns behave as poorly differentiated regardless of their degree of differentiation and include papillary serous carcinoma. In 95% of cases. Precursor for prostatic cancer:  Androgens level is high. A capsule that rahges from delicate collapsed reticulin to welldefined connective tissue usually separates the lesion from the surrounding parenchyma. lumbar spine.  Nodular hyperplasia. 3. encapsulation may not be macroscopically evident. yellow-tan. iliac and para-aortic lymph nodes. 2. Malignant tumors 1. 4. Although they are usually well demarcated. brain. liver cell adenomas are composed of sheets and cords of cells that may resemble normal hepatocytes or have some variation in cell and nuclear size.  Microscopically. Although classification as a poorly differentiated adenocarcinoma typically requires a less of glandular differentiation and the presence of solid growth. Clinical prostatic carcinoma is the type detected by rectal examination and other investigations and confirmed by pathologic examination of biopsy of the prostate. There are following 4 types carcinoma of the prostate: 1.61   Squamous elements most commonly are histologically benign in appearance (called adenocarcinoma with squamous metaplasia or more traditionally. there are 4 histologic types of cancer of the prostate adenocarcinoma. Bile duct adenomas are firm. the prostate may be enlarged. normal in size or smaller than normal. frequently found in a subcapsular location. Clinical carcinoma.

 Cholangiocarcinomas are rarely bile stained because differentiated bile duct epithelium does not synthesize pigmented bile. 1.  All patterns of hepatocellular carcinoma have a strong propensity for invasion vascular channels. The most common type is papillary carcinoma. Hepatocellular carcinoma range from well-differentiated to highly anaplastic undifferentiated lesions. It produces high levels of adrenaline/noradrenaline hormones and their breakdown products.  When discrete masses can be seen. creamy cut surface that changes to dark brown almost instantly when exposed to air. cells recognizable as hepatocytic in origin are disposed either in a trabecular pattern or in an acinar.  Most are well-differentiated sclerosing adenocarcinomas with clearly defined glandular and tubular structures lined by somewhat anaplastic cuboidal to low columnar epithelial cells.  Supporting connective tissue is minimal to absent. Cholangiocarcinomas resemble adenocarcinomas arising in other parts of the body.” 2.  In well-differentiated and moderately well-differentiated tumors. due to oxygenation of tumor pigments.  Hepatocellular carcinoma sometimes takes on a green hue when composed of welldifferentiated hepatocytes capable of secreting bile. both of which are excreted in the urine and can be estimated as a diagnostic test. Pheochromocytoma consists of secreting cells of the adrenal medull. Mucus is frequently present within cells and the lumina but not bile. Despite the fact that the tumor is usually small and nonmetastatic. and tends to metastasize via lymphatics to nodes in the neck. This tumor occurs in young men and women (20 to 40 years of age) with equal incidence.  All three patterns may cause liver enlargement (2000 to 3000 gm). These neoplasms are often markedly desmoplastic. pseudoglandular pattern. Pheochromocytoma is one of the causes of surgically treatable systemic hypertension. it is a hazardous condition with high perioperative mortality. It has a good prognosis.62 widely and some times involving the entire liver. they are basically yellow-white.  A distinctive variant of hepatocellular carcinoma is the fibrolamellar carcinoma. it is one of the tumors that characteristically spread to bone. Tumors of the adrenal medulla       The two principal types of tumour of the adrenal medulla are pheochromocytomas (occurring in adults) and neuroblastomas (occurring in children). hard “scirrhous” tumor with fibrous bands coursing through it. Histologically it is composed of well-differentiated polygonal cells growing in nests or cords and separated by parallel lamellae of dense collar bundles. Patients may occasionally present with a spontaneous fracture due to metastatic disease. particularly the unifocal massive and multinodular patterns. cardiac failure. 2. Thyroid cancer There are four main types of malignant tumor derived from thyroid follicle cell. Macroscopically. . There may be intractable. and often unexplained. It is often multifocal within the thyroid. vanyl mandelic acid (VMA) and homovanillic acid (HVA). and has a distinctly better prognosis. the tumor is usually spherical and less than 5 cm in diameter. has no association with HBV or cirrhosis factors. Follicular carcinoma most commonly affects middle-aged people.  The diffusely infiltrative tumor may blend imperceptibly into a cirrhotic liver background. It is slow-growing and has an excellent prognosis. but the hypertension eventually becomes constant. Metastasizing via the bloodstream. explaining the soft consistency of most hepatocellular carcinoma. before the primary tumor is detected. Bile may occasionally be seen in canalicular spaces or lumens between tumor cells. It usually constitutes a single large. The excessive amine production produces hypertension that is often initially paroxysmal and associated with severe headaches. 3. it has a pale. punctuated sometimes by areas of hemorrhage or necrosis. irregular calcification. hence the name “fibrolamellar. a well-differentiated tumor that arises most frequently in young adults. so dense collagenous stroma separates the glandular elements. even metastatic tumors grow slowly and can be cured by surgical resection. and bile canaliculi may be present ultrastructurally. atypical cells. Medullary carcinoma is a less frequent derived from parafolicular or C-cells and characterised by fibrovascular septa and amyloid-conteining stroma.

 The etiology of these tumors is obscure. undifferentiated and round. while the rest have either hyperplasia of many islands. 70% have a solitary adenoma. formerly "MEA". 4) tissues of musculoskeletal system. low measured plasma glucose (hypoglycemia). PP-omas ("P-cell tumors"): no syndrome despite huge amounts of pancreatic polypeptide Multiple Endocrine Neoplasia Syndromes ("MEN". 3. insulin. 2. parathyroid adenoma. loss of potassium. produce an insulin-like activity (probably somatomedin. medullary carcinoma of the thyroid  MEN IIb/III: Medullary carcinoma of the thyroid.  Metastatic spread remains the only reliable criterion for malignancy in these tumors. "VernerMorrison syndrome"): pancreatic cholera (horrible diarrhea). especially related to fasting or exercise. gastrinomas. pancreatic polypeptide (PP). must be distinguished histologically from malignant lymphoma.  The tumors are usually slow-growing. etc. the latter can also affect the thyroid in the elderly. vasoactive intestinal polypeptide (VIP). there's not even an important genetic syndrome. .000 people)  Look for Whipple's triad: 1. mucosal neuromas. even when malignant (10% of total. adenomas): some or all of the following in same family:  Wermer's MEN I: pituitary adenoma. attacks relieved by glucose administration. The majority of gastrinomas are low-grade malignancies. patients become massively obese. but is more responsive to treatment. Tumors secreting vasoactive intestinal polypeptide ("VIPomas". MESENCHYMAL TUMORS In ontogenesis. It may present with a rapidly enlarging thyroid mass causing tracheal compression or jugular vein invasion.000. and occasionally other tumors. which are usually small. mesenchyma gives the beginning to 1) connective tissue. such as the trachea and soft tissues of the neck. higher for glucagonomas. Delta cell tumors ("somatostatinomas"): diabetes. 2) vessels. Pancreatic islet cell tumors   Islet cell tumors may be hormonally inactive or may produce hyperfunction.  Gastrinomas occur in the wall of the duodenum. The cells of the tumor. These produce mild diabetes. gallstones. sore tongue.63 4. May be benign and malignant. ACTH-omas and somatostatinomas). 3) muscles. and necrolytic migratory erythema. diarrhea. Entirely confined to the elderly.  Often. Zollinger-Ellison  Sipple's MEN II(a): Parathyroid adenoma. achlorhydria -excellent response to somatostatins. These tumors make one or more of the following: glucagon. "G-cell tumors")  An especially troublesome syndrome of multiple bleeding ulcers and diarrhea. The prognosis is very poor. mental changes.  The surrounding pancreatic islets may show hyperplasia. Don't miss this diagnosis.  Many mesotheliomas and retroperitoneal fibrosarcomas.  Grossly: usually solitary and well-encapsulated. They are named according to their histogenesis: Beta cell tumors ("insulinomas")  the most common islet cell tumors (* but their incidence is only about 1 in 1.  High basal acid secretion plus a marked increased in serum gastrin levels in response to secretin administration strongly suggests gastrinoma. somatostatin. extensively invading tissues near the thyroid. Size from0/5 to 10cm.  Microscopically: cords and sheets of well-differentiated B-cells which do not differ from normal cells. anaplastic carcinoma grows very rapidly. Gastrinomas (Zollinger-Ellison Syndrome. pheochromocytoma. gastrin. Marfanoid habitus. or a beta cell carcinoma. Glucagonomas ("alpha-two cell tumors").  Of beta-cell tumor patients. pheochromocytoma. but it varies).

More often it is located in the skin of the legs. Histologically. and abundant mitotic figures. There are giant polynuclear cells with lipids and hemosiderin between cells.small fibrous node with yellow-brown color. It produces metastases more frequently. including loss of the structure.  Poorly differentiated fibrosarcoma. 7) bone tissue. breast.  Microscopically.  Soft (loose connective tissue with great amount of stroma cells -fibroblasts and fibrocytes). . granular-cell tumor). There are 3 types of fibrosarcoma:  Differentiated fibrosarcoma is characterized by prevalence of fibrous component over cellular component. fleshy. slow-growing fibrosarcoma of the skin. and neck. 3) muscular tissue. 6) hemopoietic system. It may develop in every site where there is fat tissue. Malignant connective (fibrous) tissue tumors Macroscopically sarcoma looks like “fish flesh”. As a rule sarcoma metastases are disseminated hematogenically. usually small yellow node. 3) Dermatofibroma (histiocytoma) . or bowel wall. 6) mesothelial tissue. More often it is located on the anterior abdominal wall. mitoses are not as numerous as in fibrosarcoma.64 5) serous membranes. It looks like node or encapsulated formation. dermatofibromas are composed of intertwined and anastomosing bundles of fibroblasts surrounded by dense collagen. retroperitoneum. “tame-looking” fibroblasts that do not metastasize. 5) synovial tissue. anaplasia. termed cellular sarcoma. 2) Desmoid fibroma is a kind of dense fibroma and characterized by infiltrating growth and relapses. It is composed of banal.  Round-cell tumors of unknown origin. showing spindled and polygonal cells.  Grossly. shoulder. infiltrative. 2) fat tissue.  The overlying epidermis is thinned and there often is microscopic extension into subcutaneous fat. They may be benign (name of the tissue + oma) and malignant (name of the tissue + sarcoma). showing increased fibroblastic cells. It is locally aggressive but rarely metastasizes. Connective (fibrous) tissue tumors Main benign connective (fibrous) tissue tumors 1) Fibroma . Mesenchymal tumors develop from 1) connective (fibrous) tissue. termed unclassified tumor. Tumors of fatty tissue Benign: 1. It is characterized by prevalence of cellular component over fibrous component. and unencapsulated but deceptively circumscribed. 4) blood and lymphatic vessels. Lipomas are encapsulated. There are also special terms (e. 1) Fibrosarcoma occurs in deep soft tissue sites. Lipoma     It is the most frequent soft tissue tumors. arising in subcutaneous regions at any site but most commonly on the back. they are multilobulated gray-white. desmoid.  Localization of fibroma is various: skin. Tumors are characterized by atypical cells. there are cellular neoplasm composed of radially oriented (“storiform”) fibroblasts. 2) Dermatofibrosarcoma protruberans (malignant histiocytoma)  It is essentially a well-differentiated. They can also arise in the mediastinum.g.a node of differentiated connective tissue with different direction of the bands:  Dense -fibrous structures prevail over the cellular elements.

These tumors may be apparent only with immunohistochemical investigation. and less commonly at other body sites. d) Pleomorphic liposarcoma are high-grade. The cells have round shape. It is subdivided into four types based on the morphologic features:  The pleomorphic type occurs in patients over 45 years. especially in children. and skin. deep soft tissues.  If stroma prevails this tumor is termed fibromyoma. Malignant: 1. a large number of mitoses (high mitotic index) are characteristic. large tumor. 2. the stomach and particularly in the uterus from pre-existing myomas.  It appears against a background of tissue shifts and is accompanied by other development defects (large masses of striated muscles). Leiomyosarcoma (malignant leiomyoma) with cellular and tissue atypism. b) Myxoid (embryonic) liposarcoma tend to be low-grade tumors. with grape-like masses projecting into a cavity such as: vagina. large with granular cytoplasm (no lipids). 3. It resembles embryonic muscular fibers and myoblasts. in the abdominal wall.  Leiomyomas occur predominantly in the female genital tract. Hybernoma is a rare tumor of brown fat and consists of large round cells with granular or foamy cytoplasm (fat vacuoles). it infiltrates to intermuscular connective tissue. hyalinosis.65  Intramuscular infiltrating lipoma is a tumor without distinct (clear) borders. esophagus. Rhabdomyosarcoma (malignant rhabdomyoma) is a more common. Leiomyoma  Leiomyoma consists of smooth muscle with chaotic (confused) location of the muscular tissue bands. botryoid. petrifaction are characterized for leiomyomas. 2. the stroma with vessels and nerves. Granular-cell tumor (Abrikosov's tumor): this is small tumor in a capsule. The botryoid pattern is basically a morphologic variant of embryonal. which are stubbornly recurrent. follow a more protracted course. hemorrhages. cysts. bladder. Liposarcoma (lipoblastic myoma) is a rare. Tumors of the muscles Benign: 1. Malignant granular-cell tumor (malignant myoblastoma) resembles malignant rhabdomyoma but the cytoplasm is granular. It is located in the tongue. It has . This variant has large. 2. in the head and neck and urogenital region. aggressive sarcomas (85-90% metastasize).  Secondary changes: necrosis. and a little number of vessels. These rare tumors arise in the skin. nipple.  Embryonal. atypical tumor cells. 2.  The tumors are most frequently primary tumor of the heart in infants and children and are frequently discovered in the first years of life because it leads to obstruction of valve orifice or cardiac chamber. Synovial sarcoma (malignant synovioma) develops around the large joints (but not in joint spaces). Malignant hybernoma is a very rare tumor with cellular polymorphism and a lot of giant cells. Tumors of synovial tissue 1. Rhabdomyoma  Rhabdomyoma consists of striated muscles. bowel wall). There may occur xanthomic cells and clefts. Malignant: 1. in the parapharyngeal region. It contains a lot of stroma with hyalinosis. There are several types of liposarcoma: a) Well differentiated (lipoma-like) liposarcoma. some showing abundant cytoplasm with cross striations characteristic of skeletal muscle differentiation. 2. alveolar types are poorly differentiated tumors of small blue cells that have focal skeletal muscle differentiation (rhabdomyoblasts with abundant eosinophilic cytoplasm or cross striations). and metastasize late. 3. but they may also occur at other body sites where smooth muscle is well represented (scrotum. which is composing of lipocytes of different degree of maturity and lipoblasts. Benign synovioma develops in the tendons and tendon sheath. c) Round-cell liposarcoma.

it is termed macroglossia. Hemangioma is a tumor from blood vessels. small. liver. gray-red. its structure is similar to fibroma (fibroid mesothelioma). more often in children. first described by Kaposi. four forms of Kaposi‟s sarcoma are described:  Classic (european) Kaposi’s sarcoma. dome-shaped nodules or plaques in the skin. Angiosarcoma also known as hemangiosarcoma and malignant hemangioendothelioma. a) Capillary lymphangioma is small. pericardium) microscopically looks like atypical large cells with vacuolized cytoplasm. The tumor is composed of capillaries surrounded by spindle-shaped pericytes outside the capillary basement mambrane forming whorled arrangement. Malignant mesothelioma may has tubular and papillary structures. bones. Lymphangiomas growth of lymphatic vessels in different direction with formation of a node or enlargement of the organ. the other have fibroblastoid atypical cells and collagen fibers. mucous membranes. A large cystic variety called cystic hydroma occurs in the neck producing gross deformity. gastrointestinal tract. Silver impregnation stains are employed to confirm the presence of pericytes outside the basement mambrane of capillaries and to distinguish it from hemangioendothelioma. Malignant tumors from blood vessels and lymph vessels 1. b) Cavernous lymphangioma is more common than capillary type.66 polymorphic structure. There are several types of hemangioma: a) Capillary. They are often 1 to 2 cm in diameter. filled partly or completely with blood. These lesions are characterized by extreme pain. structures resembling tendons. 3. Thedisease is slow and appears as multiple. liver. It is composed of a network of endothelium-lined. purple. It consists of large dilated lymphatic spaces lined by flattened endothelial cells and containing lymph. which develops in the skin. Glomus tumor is an uncommon true benign tumor arising from contractile glomus cells that are present in the arteriovenous shunts. if lymphangioma develops in the lip it is termed macrocheilia. If lymphangioma develops in the tongue. red to blue. Microscopically: the tumors are composed of small blood vessels lined by endothelium and surrounded by aggregates of glomus cells. in 1872. They are single or multiple. 2. 2. Tumors of mesothelial tissue 1. These lobules are composed of capillary-sized. gastrointestinal tract. skin. Kaposi’s sarcoma is a malignant angiomatous tumor. Cavernous hemangiomas are composed of thin-walled cavernous vascular spaces. to poorly-differentiated lesions composed of plump. blood-filled vessels. and muscles. slightly elevated lesion measuring 1 to 2 cm in diameter. spleen. The glomus cells are round to cuboidal cells with scanty cytoplasm. brain. The intervening connective tissue stroma contains some non-myelinated nerve fibres. thin-walled. liver. Pericytes are cells present external to the endothelial cells of capillaries and venules. discrete of diffuse. Malignant mesothelioma (peritoneum. the tumor has attracted greater attention more recently due to its frequent occurrence in patients with AIDS. The tumor is usually well-defined. These vessels are lined by single layer of plump endothelial cells surrouded by a layer of pericytes. 3. Some tumors have polymorphic cells and pseudoepithelial gland formations with cysts. Glomus tumor (glomus angioma). it is a malignant vascular tumor occurring in the skin. Presently. subcutaneous tissue. circumscribed. Hungarioan dermatologist. pleura. Capillary hemangiomas are well-defined but unencapsulated lobules. Malignant hemangiopericytoma is a tumor arising from pericytes. b) Cavernous hemangioma locates in the liver. muscles. soft and spongy masses. The tumors may be well-differentiated masses of proliferating endothelial cells around well-formed vascular channels. However. Mesothelioma with tubular and papillary structures is called epithelial mesothelioma. Tumors from blood and lymph vessels Benign tumors from blood vessels and lymph vessels 1. especially on the legs. Benign mesothelioma resembles a dense node in serous membrane (pleura). These tumors are highly malignant with early metastases in skin. These tumors are found most often in dermis of the fingers or toes under a nail. capillary-sized spaces containing lymph and often separated by lymphoid aggregates. . lung and retroperitoneal tissues. polypoid mass. 2. anaplastic and pleomorphic cells in solid clusters with poorly identifiable vascular channels.

2. Multinucleated. and destructive masses showing focal hemorrgage and necrosis. usually about 1 cm in diameter. The cutaneus lesions are not localized to lower legs but are more extensively distributed involving mucous membraines. especially lymph nodes and the gut.  Kaposi’s sarcoma in renal transplant cases. and/or osteoid. skull. 4. invasive. In about 10% of cases. like exostoses. Lymphangiosarcoma is seldom tumor and appears as a result of chronic lymphatic stasis. plump tumor cells. It most found in the epiphyseal ends of long bones in adults between 20-55 years of age. it is termed enchondroma. 4. and. marked osteoclast reaction. it tends to be located in the vertebrae or long bones. All form osteoid and /or bone-incorporating malignant cells. 3. and is most often located in the cortex near the ends of the tibia and femur. Their nuclei are often deeply indented or longitudinally grooved. Metastasize widely. They present as gray-white. the changes are nonspecific in the early patch stage and more characteristic in the late nodular stage:  In the early patch stage. Microscopically. hemosiderin. and does not cause as much pain. hemorrhage. The vast majority is benign. interstitial substance. Histologically. Bone tumors Benign: 1.  Epidemic (AIDS-associated) Kaposi’s sarcoma. Osteoblastic type (bone formation). thus. It found in epiphyses. breastbone. arranged in sheets. If in the center area of the bone. and sometimes surrounded by a lacelike pattern of calcification. It is found in younger age and has a more aggressive course than the classic form. Osteolytic type (bone destruction). there are irregular vascular spaces separated by interstitial inflammatory cells and extravasated blood and hemosiderin. lymph nodes and internal organs early in the course of disease. Malignant: . there are slit-like vascular spaces containing red blood cells and separated by spindle-shaped. This form is associated with recipients of renal transplants who have been administered immunosuppressive therapy for a long time. These spindle-shaped tumor cells are probably of endothelial origin. and pelvis. spine. Two types of osteosarcoma are known: 1. 2. b) compact osteoma.67  African (Endemic) Kaposi’s sarcoma. 2 types of osteoma are known: a) spongy osteoma. the tumors are composed of highly atypical fibroblastic cells and are. others largely osteoblastic. osteoclast-like giant cells may be present and abundant enough to suggest giant cell tumor of bone. classified as sarcomas. Osteoid-osteoma is a small. tumor cells are polygonal. The lesions may be localized to the skin or may have widespread systemic involvement. the osteoid is lined by osteoblasts and surrounded by fibrous tissue. Cartilage tumors Benign: 1. some chondroid. Resembling embryonic chondroblasts. Benign chondroblastoma (Godman’s tumor) consists of chondroblasts. usually to lung first but also to other organs and bones (lymph node metastases are rare). osteoclast-like. 2. but rare examples have metastasized to lung. Giant cell tumor of bone (osteoblastoclastoma) is mostly benign but locally aggressive tumors that tend to recur if not removed completely. The histologic pattern is one of uniformly distributed. There may be foci of necrosis. Chondroma derives from hyaline cartilage in the feet. multinucleated giant cells in a plamp spindle-cell background. Benign osteoblastoma (giant osteoid osteoma) is larger than osteoma (greater than 2 cm). They locate in the medullary cavity of the metaphyseal ends of long bones. Malignant: Osteosarcomas (osteogenic sarcoma) compose of bone-forming cells. Osteoma composes of mature compact bone and develops as a rule in spongy and tubular bones.  In the late nodular stage. Some are largely fibroblastic. and others highly vascular (telangiectatic). If tumor is located in the peripheral area of the bone it is termed ecchondroma. The disease begins in the skin but grows rapidly to involve other tissues.

partly mucinous. which are also a part of this system. irregular. The highest incidence is observed between the ages 25 . their processes form thick interlacing. Vegetative. and the spongiosa is invaded. Hyalinosis and calcification may also be observed.existing chondromas. two or more cells in the lacunae. when calcifications are present it may be dense. They do not always have distinct boundaries with the surrounding tissue. more often along the walls of the ventricles. Primary chondrosarcoma originates in bones the trunk (pelvis. 2. Fibrillar tumor is rich in glial fibers looking like parallel bands. Cerebellar astrocytoma and subependymal astrocytoma are separate subtypes. glassy consistency. It may be primary and secondary. Its consistency may be paste-like. pleomorphism. partly hemorrhagic areas of necrosis as well as pseudocysts.  Secondary chondrosarcoma develops from pre. The metastases spread through the liquor routs. 3. more seldom in the region of visual tuber and in the trunk. In rare cases. Astrocytoma is characterized by cyst formation (one or several).40. the tumor is pinkish-gray. considerable enlargement of the brain portions is observed. They are mainly localized in the large hemispheres of the brain. A malignant type of the tumor is oligodendroglioblastoma characterized by special cell location. Protoplasmatic astrocytoma consists of different in size cells with processes. 2. they occur in children. As a rule. 4. they develop in the area of cerebellum and spinal cord. The types of oligodendrogliomas are fusiform cell and polymorphocellular. it disseminates through the liquor routs. The highest incidence is observed at the age of 30 . which resemble astrocytes. A malignant type is astroblastoma characterized by rapid growth. This tumor is rare.68 Chondrosarcomas are malignant tumor consisting of cartilage. . Fibrillar-protoplasmatic tumor is characterized by even location of astrocytes and glial cells.  The cortex is breached in several areas. They develop from astrocytes and can be found in all brain portions. Very seldom. it contains small amount of astrocytes.  Depending on their location. there are peripheral and central chondrosarcomas. There are three histological types of astrocytoma: 1. The tumor is usually poor in vessels. marked polymorphism with giant cells. resembles brain substance and is diagnosed by the enlargement of the brain portion. Mesenchymal elements. Primary multiple oligodendrogliomas of meninges and visual nerves were also described. polymorphism and necroses in the tumor. Microscopically it consists of homogeneous small cells with round nuclei and narrow outline of cytoplasm. They contain colloid substance or yellowish fluid with large amount of protein. vertebrae.  TUMORS OF NERVOUS SYSTEM AND BRAIN MEMBRANES Tumors of nervous system develop from different elements of the nervous system: 1. Peripheral.  Microscopically: atypical cartilage with plump nuclei.  There are also characteristic. which is poorly colored. The diameter of the tumor is about 5-10 cm. frequent multinucleated cells. ribs) and adjacent proximal ends of long bones of the extremities. It is also characterized by numerous mitoses and necrosis foci. Symmetrical location of the tumor nodes in the walls of the ventricles is typical. Oligodendroglial tumors        In the majority of cases these are benign.45. Sometimes it is characterized by the structure resembling honeycombs. 3. Astrocyte tumors or gliomas        The most frequent brain tumors. Macroscopically. Central.  The tumor tissues have a graish-white. It is homogeneous on incision.

3) Neuronal tumors:  Ganglioneuroma is a rare mature tumor. medulloblasts. Heterotopic types are rare (horse‟s tail). This is an extremely rare tumor of CNS. and then become extramedullar. 1) Ependymoma (glioma connected with ventricular ependymoma) looks like intra. It grows quickly.  Macroscopic study demonstrates well-outlined nodes of various sizes. . The cells grow like sincitium. Mitoses are numerous.69 Ependymal tumors and tumors of choroid epithelium Three types of ependymal tumors are distinguished. spongioblastoma. villous structures of cubic or prismatic epithelial cells. It occurs mainly in children. The surface of the tumor is small. the color is pinkish-gray. seldom in the hemispheres of the brain. Papillary cancer is a rare tumor. Choroid papilloma is a tumor from the epithelium of vascular plexus.  Microscopic study reveals perivascular structures of radially located cells. 2) Ependymoblastoma is a malignant type of ependymoma. The latter occurs in children. Consistency is either dense or soft. 2. Single and multiple clefts and tubes bedded with cylindrical epithelium are common. It is located within the brain ventricles.  Ependymoma is usually localized in the bed of the 4th ventricle and in the 3th ventricle.  It consists of numerous. Poorly differentiated and embryonic tumors Medulloblastoma and glioblastoma belong to this group. 1. their connective-tissue stroma is covered with cubic or cylindrical epithelium. looking like a villous node in the cavity of the brain ventricle.  Metastases spread through the liquor routs.  Ganglioneuroblastoma is a malignant analogue of ganglioneuroma (malignant gangliocytoma). The tumor is formed from large cells with bubble-like nucleus. Most frequently it is localized in the bed of the 3th ventricle.or extraventricular node.  The foci of necrosis and cysts can be found in it  Clasters of uni. has cauliflower.and bipolar cells around the vessels (so-called pseudorosettes) and cavities covered with epithelium (true rosettes) are typical. Their processes form a fibrous ring between the body of the cell and the wall of the vessel and over the body of the cell. 2. Choroid carcinoma.  Microscopically it consists of villi.  Macrpscopically. in the cerebellum it looks like hyperplastic folds. Rosette is typical.  Most frequently they are located in caudal portions of rhomboid fossa.  Macroscopically they look like nodes of different size with tuberous (4th ventricle) or villous (lateral ventricle) surface. it is pinkish-gray. Vessels are not numerous. Hyalinosis can be frequently observed. In the medulla oblongata it is diffuse. metastases spread through the liquor system. There are a lot of vessels. Ependymoma may go down the spinal canal (craniospinal tumors).  The most frequent idealization is vermis cerebelli. Glioblastoma is the second (after astrocytoma) in the incidence. This is characterized by marked cellular polymorphism. In the rest of the tumor tissue. It is characterized by cellular polymorphism and similar to malignant glioma. Macroscopically ganglioneuroma looks like a limited node. It is made of anaplastic cells covering the vascular plexus.  Microscopically medulloblastoma consists of homogenous small cells with dark round or oval nucleus and poorly seen rim of cytoplasm. Choroid carcinoma is a malignant type of choroidpapilloma. It usually occurs in children and juveniles.  Neuroblastoma is a rare highly malignant brain tumor. Synonyms: multiform glioblastoma.or large-villous. The tumor consists of mature ganglionic cells divided with the bands of glial stroma. they first grow intramedullary.or mulberry-like appearance. The color is pinkish-gray.  It is mainly observed in young people.  In the area of the spinal cord. the consistency is soft. 1.  Cerebellum ganglioma is characterized by proliferation of large nervous elements of Purkinier's cell type. Medulloblastoma is a tumor made by immature cells. Mitoses are numerous. The cells are located close to each other. glioblastoma. Dedifferentiated ependymoma is a transitory form between the two types: Choroid papilloma. the cells are located in mosaic manner. therefore it is highly malignant.

elastic. 8) tentorium cerebelli. 2. vasomotor vascular crises. Endotheliomatous. from small lymphocyte-like to giant polynuclear. cerebrospinal nerves. sympathetic trunks. sometimes in the trunk. paraganglioma (glomes tumor. 1. while in children. hemorrhages and vascular growths are typical. their consistency is dense. psammoma bodies. paste). chemodektoma) belong to this group. and diffuse sarcomatosis of the meninges. ganglioneurocytes) in sympathetic ganglia as well as from the cells of nonchromophinic paraganglia (glomes) genetically connected with sympathetic nervous system. The tumor . which appear due to the influence on the craniobasal and distal regions of the brain. 2. Macroscopically it is motley-colored due to necroses and hemorrhages.  Macroscopically.  Microscopically large endothelium-like cells characterize it. epileptiform attacks. Meningotheliomatous characterized by microcircular structures. Xantomatous. heart failure.  Ganglioneuromas are localized in the medullar substance of the adrenal gland. they are rare. regional foci of circulation disturbance (insults and hemorrhages). 3.  Special attention should be paid to development of secondary signs. 7) the region of semilunar node of trigeminal nerve. their size and shape are various. 9) vascular plexi. This tumor is mainly located in the large hemispheres of the brain. band-like). 5) wings and body of main bone. It is situated in the white substance of the brain. wedging of cerebellum tonsil to the great foramen. They mainly occur in adults over 30. Tumors of vegetative nervous system Tumors of vegetative nervous system originate from ganglionic cells of different degree of maturity (sympathogonias. The cells usually form groups (plate-like. It is also termed psammoma. Glioblastoma usually produces regional metastases. 6) tubercle of the saddle. multiple) nodes.70       It occurs at the age of 40 . Such benign tumors as ganglioneuroma. morphogenetic variety of CNS tumors.  Only correct diagnosis helps to determine the tactics of treatment for such patients. Meningovascular tumors These tumors appear from the meninges. entrance of the temporal lobe to the tentorial foramen with strangulation of the midbrain.  Types of arachnoidendotheliomas: 1. difficult diagnosis and differential diagnosis as well as their localization allow including them into a separate group.  Secondary syndromes are dislocation syndromes which are dangerous for the life of the patient. The tumor is on incision they are grayish-pink with light bands. those to the inner organs are rare (lungs). Arachnoidendothelioma (meningioma)  Arachnoidendothelioma (meningioma) is the most frequent type of meningovascular tumors. 2) convex. curl-like. sympathoblasts. Microscopically the tumor is characterized by marked polymorphism. arachnoidendothelioma looks like well-limited solitary (in rare cases.  Arachnoendothelioma is usually localized in I) longitudinal sinus and Paccionian bodies. 5. Necroses. 3) falciform process. polymorphocellular sarcoma. The cells are located disorderly (cellular chaos). 4.  Thus. Fibrous arachnoidendothelioma with plenty of connective tissue fibers.  Histologically it resembles fibrosarcoma.60. there are secondary changes (calcifications.  They are characterized by slow expansive growth. Meningeal sarcoma is malignant type of the tumor. 4) olfactory region. Mitoses and centers of atypical division are frequent. In these tumors. so-called endotheliomatous structures. Alveolar. The most frequent is meningioma and its malignant variant meningeal sarcoma. It usually develops in young patients. It is characterized by rapid infiltrative growth without distinct boundaries.

slightly granular.  Nevi are benign tumors of skin consisting of melanocytes of epidermis and derma. 4.  Malignant neurilemma is neurogenic sarcoma. Intradermal nevus. neurofibromatosis (Recklinghausen‟s disease) are benign ones. and nuclear decentralization.  According to the WHO classification (1974). The cells in mature nevi may be polynuclear.  They look like brown spots of different size. Malignant paraganglioma. 5. Ganglioneuroblastoma occupies an intermediate place. The tumor does not produce metastases. This is characterized by cellular polymorphism. Epithelioid nevus or juvenile melanoma can often appear on the face. Macroscopically they have papillomatous appearance and may contain hairs. Involution nevus (fibrous papule of the nose). 8. Their-cytoplasm is homogeneous. Junctional nevus. Pilymorphocellular atypism.  Schwannoma is formed of spinder-like cells with rod-shaped nuclei. Thus. They resemble nests. Schwann‟s glia is represented by satellite cells. It can produce ACTH and serotonin. The nests are round or oval. Sometimes it matures and turns into ganglioneuroma. Epithelioid nevus (intracellular). It consists of connective tissue with nervous cells. the tumors of peripheral ganglias correspond to different stages of their embryonic structure. Giant pigmented nevus. The nevus cells are localized in the area of reticular layer apices. 6.71    differs from normal ganglia as it has the signs of atypism (polynuclear cells. Neurilemma (Schwannoma). small intramural ganglia of the inner organs. It looks like flat or ball-like node. garden-like structure is characteristic. It may be large. The tumor is localized in the middle ear. medullar layer of adrenal glands and sympathetic trunks. Neurogeneous origin of melanocytes is generally recognized. TUMORS OF MELANIN-PRODUCING TISSUE Melanin-producing cells (melaninocytes) are of neurogeneous origin. The cells and fibers form rhythmical structures. 10. Cellular blue nevus. 2. It resembles the tumors of APUD system (APUDomas). sometimes- . It may be localized in any region of vegetative nervous system. its histological structure is alveolar and trabecular with large number of sinusoid vessels. there are the following types of nevi: 1. Together with the nevus cells located on the border of dermis and epidermis. lymphogenic metastases. Lest mature is neuroblastoma. Balloon-cell nevus. 9. there are nests of nevus cells in derma itself. Some of them can be found on the border between derma and epidermis. Intradermal. Junctional nevus. Halo nevus. polynuclear symplasts. especially in children. tigrolysis. Sometimes their size is enormous (giant pigmented nevus). Blue nevus. the most manure is ganglioneuroma. The nevus cells look like compact mass. They may become the origin of tumor-like formations (nevi) and melanomas. 3. infiltrating growth. retroperitoneally. Compound nevus. The surface of the skin is smooth. Nevus cells are located only in derma. The tumor develops intrauterinely or during the first years of life. Compound nevus. Nests of nevus cells are found on the border of epidermis and dermis. neurofibroma. Neurofibroma is a tumor connected with the nerve membrane. 7. Malignant ganglioncuroblastoma is a combination of neuroblastoma and ganglioneuroma. Tumors of peripheral nervous system Tumors of peripheral nervous system originate from the nerve membranes. Nevi are defects of development of neuroectodermal pigment elements. This may be peripheral and central. bodies and fibers. and may be either flat or elevated over the surface or be wart-like.  Neurofibromatosis is a systemic disorder characterized by development of multiplies neurofibromas associated with different development defects. Nonchromophilic paraganglioma is a benign variant.

This variant carries the worst prognosis. The cells have light basophilic cytoplasm and hyperchronic nuclei. there are a lot of mitoses. island. Lentigo maligna melanoma. This often appears as an elevated and deeply pigmented nodule that grows rapidly and undergoes ulceration. spinal cord. Histologically. It is essentially a malignant melanoma in situ. Epithelioid cells with large foamy light cytoplasm may be present. it spreads through the lymphatic and hematogenic routs. brain. where they may be seen in large number. its shape is round or oval. Acute leukemias. Melanoma Melanoma is one of the most malignant tumors. acute leukemias are characterized by the presence of very immature cells (called blasts) and by a rapidly fatal course in untreated patients. In the tumor. They are associated with replacement of normal marrow elements by a sea of proliferating “blast cells” that do not seem to undergo normal maturation. The amount of melanin is small. Blue nevus. Mitotic figures are often present and multinucleate giant cells may occur. Thus. General characteristic      In the major. Depending upon the clinical course and prognosis. They may be epithelioid or spindle-shaped. and adrenals. Some amount of inflammatory infiltrate is present in the invasive melanomas. at least initially. The type of acute and chronic leukemia is established on the basis of cytochemical peculiarities of tumor cells. Undifferentiated. On the other hand. lymph nodes and other tissues throughout the body. These tumor cells may be arranged in various patterns such as solid masses. The tumor often undergoes ulceration an early metastases. body and extremities. meninges. This often develops from a pre-existing lentigo. leukemias are classified on the basis of the cell type involved and the state of maturity of the leukemic cells. Myeloblast. Acute leukemias: 1. spleen. and medullar layer of adrenal glands.or polynuclear cells resemble Teuton’s cells. cutaneus malignant melanomas are of the following 4 types: 1. chronic leukemias are associated. This is a slightly elevated lesion with variegated color and ulcerated surface. it may also be absent. palms and mucosal surfaces. with welldifferentiated (mature) leukocytes and with a relatively indolent course. they grow as loose nests lacking the typical features of maturation. These cells may also infiltrate the liver. alveoli etc. LEUKEMIAS Leukemias are malignant neoplasms of the hematopoietic stem cells characterized by diffuse replacement of the bone marrow by neoplastic cells. liver. The tumors are localized on the skin. Classification of the leukemias I. it does not elevate over the surface of the skin. 4. melanoma cells are larger than nevus cells with irregular nuclei and prominent eosinophilic nucleoli. pigment membrane of the eye. share important morphologic and clinical features. Macroscopically this looks like bluish or bluish-brown or bluish-gray sport. 2. Melanomas may not contain pigments. 2. Uni. It often develops from a superficial spreading melanoma in situ. sheets. hemorrhages and necroses. Sometimes marked acanthosis is present. Melanin pigment may be present or absent without any prognostic influence. . the nature and extent of the vertical growth phase determines the biologic behavior and prognosis. Superficially disseminated melanoma (invasive melanoma). Nodular melanoma. the leukemic cells spill over into the blood. in rare cases mucous membranes. Metastatic spread of melanoma is very common and takes place via lymphatics to the regional lymph nodes and through blood to distant sites like lungs.72 papillomatous changes are observed. Microscopic examination reveals stretched melanocytes. Microscopically it looks like compound nevus with borderline changes. Although morphologic variants of the radial growth phase have been described. Traditionally. 3. There are a lot of vessels. 70% of melanomas develop on the skin of the face. Acral lentigenous melanoma. Mitoses are not numerous. This occurs more commonly on the soles. despite differences in their cell of origin.

73
3. Lymphoblast.
4. Plasmoblast.
5. Monoblast.
6. Erythromyeloblast.
7. Megacaryoblast.
II. Chronic leukemias:
1. Of myelocyte origin:
 Chronic myeloid.
 Chronic erythromyelosis.
 Erythremia.
 True polycytemia (Vaquez-Osler syndrome).
2. Of lymphocyte origin:
 Chronic lympholeukemia.
 Skin lymphomatosis (Sezary’s disease).
3. Paraproteinemic leukoses:
 Myeloma.
 Primary macroglobulinemia (Valdenstrem’s disease).
 Heavy chain disease (Franklin’s disease).
4. Of monocyte origin:
 Chronic monocyte leukemia.
 Histiocytosis.
Classification based on the number of leukemic cells in 1 mcl of blood:
1. Leukemic (tens and hundreds thousand leukemia cells per 1 mcl).
2. Subleukemic (not more that 15.00%-25.000 per 1 mcl).
3. Leukopenic (leukocyte count is reduced but leukemia cells can be found).
4. Aleukemic (leukemic cells in the blood are almost absent).
Morphology of all leukemias








There are two aspects to the morphologic features of leukemia:
1. The specific cytologic details of the leukemic cells seen in periferal blood smears and
bone marrow aspirates.
2. The tissue changes produced by infiltrations of leukemic cells.
The tissue alterations produced by various leukemias are often similar and may be
separated into primary changes, attributed directly to the abnormal overgrowth or
accumulation of white cells; and secondary changes, caused both by the destructive effects
of masses of these cells and by their relative infectiveness in protecting against infection.
Although leukemic cells may infiltrate any tissue or organ of the body.
Leukemic infiltration of hemopoietic organs (bone marrow, spleen, lymph nodes) at first,
then of the other organs (mucous membranes, myocardium, kidneys, brain, vessels, etc.).
The most striking changes are seen in the bone marrow, spleen, and liver: massive
splenomegaly, lymhp node enlargement, enlargement of the liver.
Pyoid bone marrow due to proliferation of the tumor cells (mature or immature,
respectively) in the bone marrow with displacement of the red sprout. Macroscopically,
bone marrow is grayish-whitish.
Necrotic tonsillitis, gingivitis develops due to leukemia infiltration of the oral mucosa and
tonsils against a background of immunogenesis inhibition. Besides, infiltrates in the gingiva
are particularly characteristic of monocytic leukemia.
The secondary changes of all forms of leukemia are:
a) Anemia and thrombocytopenia, especially in acute leukemia.
b) The bleeding diathesis.
c) Petechial and ecchymoses.
d) Hemorrhages into the serosal linings of the body cavities, mucosal
hemorrhages etc.
e) Disseminating intravascular coagulation may also lead to widespread bleeding.
f) And, finally, infections and sepsis are a prominent feature, especially in acute
leukemias.
Foci of extramedullary hemopoiesis develop in the liver, spleen, kidneys, and lymph nodes.
There is compensatory adaptation reaction directed to restoration of the red sprout.

74
Distinctive features of acute and chronic leukemia are:
1) Bone marrow and blood picture (in acute leukemia blasts are observed, in chronic mature
cells are found).
2) Leukemic failure (hiatus leukemicus) characterizes acute leukemia. It is sharp increase of
blast count and single mature elements while transitional forms are absent.
3) Sharp enlargement of the spleen, liver, kidneys and lymph nodes characterizes chronic
leukemia while in chronic one it is less marked. The spleen can weigh 6 - 8 kg, the liver 5 - 6 kg.
Complications and causes of death:
1) Hemorrhage to vital organs (brain).
2) Ulcerative necrotic and septic complications (sepsis).
Chronic myeloid leukemia (CML)
Chronic myeloid (myelogenous, granulocytic) leukemia comprises about 20% of all leukemias
and its peak incidence is seen in 3rd and 4th decades of life. A distinctive variant of CML seen in
children less than 3 years of age is called juvenile CML.
Clinical Features
At research of chromosome clearly recognize Philadelphia chromosome, associated with poor
prognosis.
 Leukemic infiltration contains myelocytes and metamyelocytes.
 Pyoid bone marrow.
 Features of anemia such as weakness, pallor, dyspnoe and tachycardia.
 Symptoms due to hypermetabolism such as weight loss, lassitude, anorexia, night sweats.
 Splenomegaly and hepatomegaly is almost always present and is frequently massive.
 Bleeding tendencies in blast crises.
 Less commonly, features such as gout, visual disturbance, neurologic manifestations and
priapism are present.
 Juvenile CML is more often associated with lymph node enlargement than splenomegaly.
Chronic lymphocytic leukemia (CLL)
Chronic lymphocytic leukemia constitutes about 25% of all leukemias and is
predominantly a disease of the elderly (over 50 years of age) with a male preponderance (male-female
ratio 2:1).
Clinical Features:
 Features of autoimmune hemolytic anemia such as weakness, fatigue and dyspnoe.
 Enlargement of superficial lymph nodes.
 Splenomegaly and hepatomegaly are usual.
 Hemorrhagic manifestations are found in CLL with thrombocytopenia.
 Infections, particularly of respiratory tract, are common.
Paraproteinemic leukemias







The most important of this group is myeloma.
The disease is characterized by growth of tumor lymphoplasmocytic cells (myelomic cells)
in the bone marrow and other organs.
Bone marrow myelomatosis causes bone destruction. Sinusal resorption of the bone results
in osteolysis and osteoporosis. The bones become fragile.
Hypercalcemia develops due to their destruction; it may be followed by development of
calcific metastases.
Myelomic-cell infiltration develops in the inner organs: spleen, lymphatic nodes, liver,
kidneys, lungs, etc.
A number of changes are associated with secretion of paraprotein by the tumor cells. These
changes are amyloidosis, paraproteinemic nephrosis or myelomic nephropathy resulting in
shrunken kidney.
Depending on the character of myelomic cells, myelomas are divided into:
1. Plasmocyte.
2. Plasmoblast.
3. Polymorphocellular.
4. Small-cell.

75

Morphologically, depending on the character of myelomic infiltrations the following forms
are distinguished:
1. Diffuse.
2. Diffuse nodular.
3. Multiple nodular.
Causes of death are uremia, sepsis, necrotic changes, and amyloidosis.

LYMPHOMAS



Lymphomas are malignant neoplasms characterized by the proliferation of cells native to
the lymphoid tissues that is lymphocytes, histiocytes and their precursors and derivatives.
Like other neoplasms, all lymphomas are of monoclonal origin.
Two distinct clinicopathologic groups are distinguished:
I. Hodgkin‟s lymphoma or Hodgkin‟s disease (HD).
II. Non-Hodgkin „s lymphomas (NHL).

Non – Hodgkin’s lymphomas










The usual presentation of Non-Hodgkin‟s lymphomas (NHL) is a localized or generalized
lymphadenopathy.
However, in about one-third of cases it may be primary in other sites where lymphoid tissue
is found, for example, in the oropharyngeal region, bone marrow, gut and skin.
All forms of lymphoma have the potential to spread from their origin in a single node or
chain of nodes to the other nodes, and eventually to disseminate to the spleen, liver and the
bone marrow.
There are some important principles of classification of NHL.
As all tumors of the immune system, NHLs may originate in T-cells, B-cells, or histiocytes.
The vast majority of NHL is of B-cells origin; the remainder is in large part of T-cells
tumors.
Tumors of histiocytes or macrophages are quite uncommon.
Histologically, the lymphoma cells exhibit two different growth patterns: they are either
clustered into identifiable nodules (nodular lymphoma) or spread diffusely throughout the
node (diffuse lymphoma). In general, nodular (or follicular) architecture is associated with
a significantly superior prognosis to that of diffuse pattern.
It may be recalled that normal B cells form follicles within lymph nodes; malignant B cells
tend to recapitulate this behavior with nodule formation. Not surprisingly, therefore,
nodular lymphomas are composed exclusively of B cells.
There are some categories of NHL. Every of this category includes some subtypes of
leukemias with their own morphological features:
1. Low-grade.
2. Intermediate-grade.
3. High – grade.

Low-Grade Lymphomas
This category includes three tumors: small lymphocytic lymphoma; follicular, predominantly
small cleaved cell lymphoma; and follicular, mixed (small cleaved and large cell) lymphoma.
Small Lymphocytic Lymphoma (SLL)



This pattern makes up approximately 4% of all NHLs and is the only low-grade lymphoma
that does not have a follicular architecture.
Microscopically: SLL consists of compact, small, apparently unstimulated lymphocytes with
dark-staining round nuclei, scanty cytoplasm, and little variation in size. Mitotic figures are
rare, and there is little or no cytologic atypia.
Involvement, of bone marrow to present in almost all cases, and in about 60% of patients
the neoplastic cells spill over into blood, evoking a chronic lymphocytic leukemia-like
picture.

Follicular Lymphomas

There are two cytologic subgroups of low-grade follicular lymphomas: follicular small
cleaved cell and follicular mixed cell type.

76




The neoplastic B cells tend to recapitulate normal lymphoid follicles, and hence they
resemble the cells seen within normal germinal centers.
Small-cleaved cells are slightly larger than normal lymphocytes, with scanty cytoplasm. The
most distinctive feature that differentiates the tumor cells from small normal lymphocytes
is their irregular “cleaved” nuclear contour, characterized by prominent clefts, indentations,
and linear enfolding.
The nuclear chromatin is coarse and condensed, and nucleoli are indistinct. Mitoses are
infrequent.
Follicular, mixed lymphomas constitute a small proportion of all follicular center cell
tumors.

Intermediate-Grade Lymphomas
There are four tumors in this category - one with a follicular architecture and the other three
with a diffuse pattern. The diffuse intermediate-grade lymphomas are distinguished on the basis of
their cellular composition.
Follicular, Predominantly Large Cell Lymphoma.

In contrast to the low-grade follicular lymphomas, the majority of the neoplastic cells are
large, with cleaved or noncleaved nuclei. Mitotic figures are also more numerous.

Diffuse Small Cleaved Cell Lymphoma.

This type is composed of small-cleaved cells that are morphologically and phenotypically
similar to those that are present in the follicular small-cleaved cell lymphoma.

Diffuse Mixed Small and Large Cell Lymphoma.





These tumors contain a mixture of small cleaved cells already described and large cells that
may be cleaved or noncleaved.
The nuclei of large cleaved cells are irregular in contour, indented, and larger than nuclei of
normal histiocytes or endothelial cells (often used as a reference in evaluating size).
The nuclear chromatin is slightly more dispersed than in a normal small lymphocyte, and
nucleoli are inconspicuous.
The cytoplasm is scant and pale.
Large noncleaved cells are up to four times the size of normal lymphocytes, with a round or
oval nucleus and one to two prominent nucleoli; the nuclear chromatin-is vesicular and
mitoses are prominent. The amount of cytoplasm is greater than in large cleaved cells and
stains pale blue.

Diffuse Large Cell Lymphoma.



This variant is the most common of intermediate-grade lymphomas.
Morphologically, these tumors contain predominantly large cells of the cleaved and
noncleaved types described above.
It should be noted that the distinction between diffuse large cell lymphomas and the diffuse
mixed variant is difficult and somewhat arbitrary.

High-Grade Lymphomas
There are 3 types of lymphomas in this category: (1) large cell immunoblastic lymphomas; (2)
lymphobtastic lymphoma, a tumor that occurs in adolescents and is associated with a characteristic
clinical presentation; and (3) small noncleaved lymphomas, which include Burkitt's lymphoma and
related B-cell neoplasms.
Large Cell Immunoblastic Lymphoma.



In some cases the tumor cells have plasmacytoid features.
These cells are four to live times larger than small lymphocytes and have a round or oval
large nucleus that appears vesicular owing to margination of chromatin at the nuclear
membrane. One or two centrally placed prominent nucleoli are usually seen.
In other cases, the turner cells may contain large multilobated (polymorphous) nuclei, or
the nucleus may be round with clear cytoplasm.

with round or oval nuclei containing two to five prominent nucleoli. with scanty cytoplasm and nuclei that are somewhat larger than those of small lymphocytes. including systemic manifestations such as fever. with two halves often appearing as mirror images of each other. “owl-eyed” nucleoli generally surrounded by a clear halo. Prominent within the nuclei are large. Characterized by a diffuse or vaguely nodular infiltrate of mature lymphocytes admixed with variable numbers of benign histiocytes. inclusion-like. The nuclear size approximates that of benign macrophages within the tumor. Most patients are under 35 years of age and have an excellent prognosis. or the single nucleus is multilobade and polypoid. admixed with a variable inflammatory infiltrate. The nuclear chromatin is delicate and finely stippled. The lacunar cell is large with single hyperlobated nucleus containing multiple small nucleoli and an abundant.77  Although features such as plasmacytoid appearance and clear cytoplasm or polymorphous nucleus is suggestive of B and T immunoblasts. The origin of HD is unknown. Small Noncleaved Cell Lymphoma. macrophages. these distinctions are not absolute. Lymphoblastic Lymphoma    The tumors are fairly uniform in size. Scatterd among these cells are the distinctive RS cells. The accumulated phenotypic and molecular studies suggest that HD is heterogeneous with respect to both the cell type involved and the etiologic agents. Burkitt's lymphomas). others may arise from B-cells or T-cells. A high mitotic index is very characteristic. the target cell of neoplastic transformation has yet to be identified with certainty. Morphology       A distinctive tumor giant cells known as the Reed-Sternberg cell (RS) is considered to be the essential neoplastic element in all forms of HD. the tumor shows a high rate of mitosis. Hodgkin’s Disease or Lymphogranulomatosis   Hodgkin‟s disease (HD) is a disorder involving primarily the lymphoid tissue. At other times there are multiple nuclei. It arises almost invariably in a single node or chain of nodes and spread characteristically to the anatomically contiguous nodes. and their identification is essential for the histologic diagnosis. and as with other tumors having a high mitotic rate (e. Variants of RS cells include uninucleated cells with prominent nucleoli.    These tumors consist of a sea of strikingly monotonous cells. The nodular form of lymphocyte predominance type is clearly B-cell neoplasm. Respectively. Lymphocytic predominance HD. which also is intensely pyroninophilic and often contains small. which are diffusely distributed among the tumor cells are often surrounded by a clear space. accounting for the presence of numerous tissue macrophages with ingested nuclear debris. it is often associated with somewhat distinctive clinical features. 2. as is cell death. It‟s separated from NHL for several reasons. lipid-filled vacuoles (better appreciated on stained imprints of the tumor). There are some subtypes of HD according to the Rye classification: 1. There is a moderate amount of faintly basophilic cytoplasm. First it is characterized morphologically by the presence of distinctive neoplastic giant cells called Reed-Sternberg’s cells. and nucleoli are either absent or inconspicuous. a "starry sky" pattern is produced by the interspersed benign macrophages. Since these benign. pale-staining cytoplasm. they create a “starry sky” pattern.g. . The nucleus is enclosed within the abundant amphophilic cytoplasm.. Second. 1. Classically it is a large cell. In keeping with its aggressive growth. and lacunar cells. Finally. most often benucleate or belobed.

Nodular sclerosis HD. 3. The reticular variant is cellular and contains highly anaplastic. There are varying proportions of lacunar cells and lymphocytes. atypical RS cells. This uncommon pattern is characterized by a paucity of lymphocytes. In this variant. and also massive foci of necrosis and sclerosis. which includes eosinophils. Septic complications. . Lymphocyte depletion HD. 4. classic RS cells are rare. plasma cells. Renal amyloidosis followed by shrunken kidney and uremia. Patients are usually older and have a very poor prognosis. 2. and histiocytes. Mixed cellularity HD is a common form of HD. Typical RS cells are plentiful. Intoxication. fine or dense collagenous bands subdivide the lymphoid tissue into circumscribed nodules. Most patients are young with an excellent prognosis The causes of death and complications 1. 3. Usually there is heterogenous cellular infiltrate.78 2. RS and their pleomorphic variants.

which can be explained by compensation mechanisms. There are three types of anemias. hypoxia may develop. They stimulate blood and hemopoietic systems. Hypoxia causes appearance of incompletely oxygenated metabolic products. bloodless”. Depending on the size of the injured vessel and the rate of the blood loss it may be acute or chronic. II. Thus. decrease in the number of erythrocytes may cause oxygen deficiency in the tissues.79 PART II.0 g/dl for males and 11. which affect central regulation of blood system as well as neuromuscular apparatus of the heart causing increase in the heart rate and acceleration of the blood flow. increased or decreased. Not only the degree of anemia but also the rate of its development as well as the degree and quickness of the organism adaptation are important. accompanied by damage of the vessel or hemorrhage from the inner organs. but indeed this term denotes a complicated symptom-complex which is characterized by changes in the number of erythrocytes and reduction of hemoglobin amount in a unit of blood volume. In adults. Numerous neurohumoral factors participate in compensation of anemic state. Anemia by increased rate of destruction of red blood cells (RBC) . These conditions are called Normovolemia. minute blood volume discharged by the left ventricle increases twice (to 8 liters instead of 4). Physicians often observe discrepancy between the severity of anemia and active condition of the patient. The anemia by blood loss (Posthemorrhagic anemias) The anemia by blood loss (Posthemorrhagic anemias) is caused by the blood loss in traumas. Only in cases of severe anemia or at high rate of adaptation. It known that erythrocytes and hemoglobin realize transport oxygen to the tissues. As a result.    I. Acute posthemorrhagic anemia . TABLE 7. Anemia is defined as a hemoglobin concentration in blood below the lower limit of the normal range for the age and sex of the individual. Classification of anemias 1 Classification Normocytic-normochromic anemia 2 Microcytic-hypochromic anemia 3 Macrocytic-normochromic anemia Examples Aplastic anemia Posthemorrhagic anemia Hemolytic anemia Anemia of chronic disease Iron-deficiency anemia Sideroblastic anemia Talassemia Perniciosus anemia (lack of vit B12) Folic acid deficiency Blood mass in anemia may be normal. Hypovolemia. i. anemias can be classified on the basis of the size and shape of RBC in peripheral smears and their content of Hb. the lower extreme of the normal hemoglobin is taken as 13. III. SYSTEMIC PATHOLOGY DISEASES OF BLOOD ANEMIAS Anemia literary means “without blood. providing physiological need of the tissues in oxygen. Hypervolemia. Anemia by impaired red cell production (deficient).5 g/dl for females. Anemia by blood loss (post hemorrhagic).e. spasm of peripheral vessels develops in anemia and blood reserves from the tissue depot (mainly from subcutaneous tissue) enter the blood circulation. Classification of anemias is based on the mechanism of production: I. Besides.hemolytic anemia. pathological processes. such as (table 7). hypoxia development. Morphologically.

 Rupture of aortic aneurysm.  In case of the fatal hemorrhage.5-1 mg daily. Anemias impaired red cell production (deficiency anemias) The anemia appearing as a result of breach of hemopoesis is called by three ways: a) deficient anemia. in the majority of cases at hemorrhages from gastrointestinal tract (ulcer. c) Defect in stem cell proliferation and differentiation. hemorrhagic diathesis. 1. Aplastic anemia. The yellow bone marrow replaced by red (hemopoetic) one.  Pulmonary hemorrhage in tuberculosis. Deficient hem synthesis: Iron deficiency anemia.  Loss of 3/4 of the total circulating blood does not cause death if it occurs slowly during several days. death occurs when half of the blood is lost. Diminished erythropoiesis may be the result of deficiency of some vital substrate necessary for red cell formation. Severe irondeficiency anemia develops. . Deficient globin synthesis: Thalassemic syndromes. b) impaired red cell production. in hemophilia.  If the hemorrhage is not fatal. lymphatic nodes and other organs. taking place in the tissue of the bone marrow. In rupture of the aortic arch.  In healthy persons. extramedullary hemopoesis may take place in the spleen. c) anemia of diminished erythropoesis. Morphological signs of hemorrhage:  Pallor of skin and internal organs. liver. 2.  Loss of 1/2 of the total blood volume is incompatible with the life. hemorrhoids).  Rupture of the heart walls due to transmural infarction.80 Examples: Massive hemorrhage from the vessels of the stomach and intestine in ulcer of the stomach and duodenum. its composition restores in 4 . The bone marrow of the flat bones proliferates and becomes bright. The death occurs before exsanguinations of the organism.  In ectopic (tubal) pregnancy. repeated slow blood loss. II. Iron deficiency anemia  Iron obtained from diet showed replace its loss (about 1 mg daily) in an adult male or in a non-menstruating female. b) Nuclear maturation defects. In some cases. loss of less than 1 liter of blood causes death due to sudden drop in arterial pressure. collapse signs. A clinic-morphological signs of anemia are a pale skin and visceral organs. 1. In hemorrhages from small vessels. the source of hemorrhage is inconsiderable and very difficult to reveal.  From the ulcers in typhoid fever. the blood loss is compensated due to regeneration processes.  Congenital anemia. 2.  Chronic post hemorrhagic anemia   This frequently develops after long. Vitamin B12 and/or folic acid deficiency: Megaloblastic anemia. therefore anemia in the organs is not marked. the smallest hemorrhages (petechia) occur under endocardium of the left ventricle (Minakov’s streaks).  In repeated hemorrhages. The prognosis of the hemorrhagic anemia depends on the rate of blood flow:  Rapid blood loss of 1/4 of the total blood volume may cause shock. while in a menstruating woman there is an additional iron loss of 0. Included in this group are: a) Cytoplasmic maturation defects.5 weeks.  Bone marrow infiltration. 1. uterine bleedings. cancer. in ankylospondylosis. even at considerable blood loss. Pure red cell aplasia:  Anemia of chronic disorders.

so called mucosal block.g. milk. Clinical features    Peripheral blood. sugars.  Prematurity. chronic aspirin ingestion. peptic ulcer. and esophageal webs.  Eldery individuals due to poor dentition. One or more of the following factors may cause it: 1.  Pregnancy and lactation. ulcerative colitis. in pregnancy. 3. at onset of menarche. citric acid. 2. Folic acid deficiency anemia. Iron is absorbed mainly in the duodenum and proximal jejunum. Iron balance in the body is maintained largely by regulating the absorptive intake by intestinal mucosal cells. It is absorbed through mucosa of stomach and ileum. atrophic glossitis.  Lungs e. Alopecia. Decreased intestinal absorption.  Spurts of growth in infancy. hemoglobinuria.  Uterine e. apathy and financial constraints.  Anorexia e. iron deficiency anemia develops. Pernicious anemia. Chlorosis (called so because of pale greenish color of skin in this disease). when it has the Castle‟s intrinsic factor. postmenopausal uterine bleeding. hookworm infestation. hematuria.ingestion of foods containing iron and recycling of iron from senescent red cells.81      The iron required for hemoglobin synthesis is derived from 2 primary sources . Increased blood loss. Absorption of non-hem iron is enhanced by factors such as ascorbic acid (vitamin C). hiatus hernia. Additional cells of fundal glands of the stomach produce it.  Nose e. amino acids. cancer of stomach and large bowel. Absorbtion of vitB12 takes place in stomach. oesophageal varices. childhood and adolescence. repeated epistaxis.  Partial or total gastrectomy  Achlorhydria  Intestinal malabsorption such as in celiac disease. associated with loss of sideroblasts and absence of stainable iron in the reticuloendothelial cells. hemorrhoids. Iron from diet containing hem is better absorbed than non-hem iron. Others organs. Megaloblastic anemia There are two principal types of megaloblastic anemia: 1. excessive menstruation in reproductive years. phytates and tannates contained in tea. 4. repeated miscarriages.g. Non-hem iron is absorbed almost exclusively as ferrous form. VitB12 enters the organism through the intestinal tract. Hyperplasia of normoblasts. Pernicious anemia .  Renal tract e. pancreatic secretions. the major form of vitB12 deficiency anemia. Iron absorption is impaired by factors like medicinal antacids. gastric secretions and hydrochloric acid. VitB12 and folic acid are necessary factors of hemopoiesis.g.g. Pathogenesis It is only after the tissue stores of iron are exhausted that the supply of iron to the marrow becomes insufficient for hemoglobin formation. diverticulosis. koilonychias. hemoptysis. Entrance of vitB12 and active folic acid to bone marrow determines normal erythropoesis and activates maturation of red blood cells. Increased requirements.  Gastrointestinal e. Inadequate dietary intake  Poor economic status. completing the Plummer-Vinson triad of hypochromic microcytic anemia. Marrow. 2. atrophies of the tongue and gastric mucosa. The connection of vitB 12 and Castle‟s intrinsic factor leads to formation of the complex of protein and vitamin. Esophageal webs may appear.g. Red cells are pale (hypochromic) and smaller than normal (microcytic).g.

 Radiation lesions (x-rays. These changes lead to sclerosis. sensory ataxia. However. 1.82       If the additional cells of fundal glands don’t product gastromucoprotein the anemia is called pernicious anemia (PA). III. The principal alterations involve the spinal cord. Hemolytic anemia with intravascular hemolysis predominates. Secondary effects of granulocytopenia (infections) and thrombocytopenia (bleeding). its wrinkles are smooth away. As a result of hemolysis of erythrocytes there is hyperplasia of bone marrow. As a result of deficiency of these cells the erythropoiesis is done in megaloblastic type. Morphology       There is general hemosiderosis as a result of disintegration of red blood cells. The liver increases in size. Folic acid deficiency anemia Folic acid deficiency induces a megaloblastic anemia that is clinically and hematologically indistinguishable from that encountered in vitamin B12 deficiency. Anemia by increased rate of destruction of red blood cells (RBC) .  Destruction of the bone marrow by cancer metastases. and thrombocytopenia (pancytopenia). It is catching hereditary. Morphology    Hypocellular marrow. thymus tumors).  Toxicoallergic (drugs). The additional cells are injured.hemolytic anemia. The glands are decreased. These anemias generate large amounts of free hemoglobin in circulation. Megaloblastic and megalocytic disintegrate in bone marrow and in the focuses of extramedullar hemopoesis and in the blood vessels too. plain.    The process of destruction is predominated. anemia.  There are many foci of extramedullar hemopoesis in lymphatic nodules. May be idiopathic or caused due to following factors:  Endocrine (hypothyroidism. sometimes followed by loss of axons. atomic energy). Hypoplastic and aplastic anemias Characterized by failure or suppression of multipotent myeloid stem cells and resultant neutropenia. Hematopoetic cells replaced by fat cells. The autoimmunity injury of additional cells takes place in this case too. These changes give rise to spastic paraparesis. glazed. Pancreas has a density consistence too (sclerosis). The major specific changes in PA are found in bone marrow. and sever paresthesias in lower limbs. cytostatic preparations. sepsis. and “beefy” (atrophic glossitis). where there is myelin degeneration of the dorsal and lateral tracts. There are two groups of this type of anemia. connective tissue and spleen. The epithelium is atrophied. etc. There are general hemosiderosis and hemolytic jaundice. radium radiation. The tongue is shiny.  There are the following courses of this type such as hemolytic poisons.  Chemical (benzene. There are antibodies against the additional cells (gastric parietal cells). They are involuated prematurely. Since this . The changes in the stomach are following: the mucosa is thin. and complications after hemotransfusions and transfusion of incompatible blood groups. hard burns.  Infectious. There is a fatty change in the parenchymatous organs as a result of hypoxia grows. Addison and Birmer described it in 1868. neurologic changes seen in the latter do not occur and gastric atrophy is absent. In the alimentary system abnormalities are regularly found in the tongue and stomach. malaria. has a density consistence and a brown color (hemosiderosis). alimentary tract and central nervous system. The processes of destruction predominate on the processes of hemopoiesis in this case. It has a pinkred color.

Cooley‟s anemia).  Enlargement of the spleen and liver. phosphorus. without light center. the molecular structure of hemoglobin is abnormal. it is essentially an intimal disease. and infarctions. Siderofibrosis caused by hemosiderin accumulation develops due to increased decay of sickle-like erythrocytes in the spleen. It is called atheroma. Nearly all of them are the result of atherosclerotic coronary disease.5 cm in diameter. 2. venom of snakes. : Thalassemia (target cell anemia. This group includes hereditary spherocytosis. spherical. The term AS derives from the combination of athero . lipidrich material in the center of a typical intimal plaque. and sclerosis (scarring). peripheral vascular disease. Atherosclerosis begins early in life and develops progressively over years.).(„porrige‟). i.e. The latter occurs due to Rh incompatibility of the mother‟s and fetus‟s blood. It includes the following forms of the disease: congenital (family) spherical-cell anemia. brightly colored. The major clinical syndromes are related with ischemia. sepsis. Activity of enzymes decreases. thalassemia. it is followed by splenomegaly and anemia. such as 1) Defects of cell membrane. referring to the soft. it is rarely symptomatic in the first three decades. etc. elliptocytosis. they cause stasis. and accumulation of macrophages.83 free hemoglobin can‟t be taken up fast enough by the phagocytic cells of the liver and spleen. The cause of sickle-cell anemia is congenital insufficiency of erythrocytes due to presence of S hemoglobin (S corresponds to sickle). Basic lesion is the patchy deposition of yellow lipid in plaques deep in the intima with overlying fibrosis up to 1. fetal erythroblastosis. but thereafter the frequency of clinical atherosclerotic events increases logarithmically. 2) Defects of enzymes. sickle-cell anemia. causing hemoglobinuria.  Hemoglobin in the primary glomerular filtrate is partially taken up by the proximal tubular cells and transformed into the hemosiderin inside the lysosome. protruding into the vessels lumen. . causing renal hemosiderosis. it is excreted through the glomeruli. Sickle-cell anemia and thalassemia are hemoglobinopathies (conditions due to abnormal hemoglobin in the erythrocytes). malaria. Every year approximately 1 million persons in the world experience either a myocardial infarct or sudden cardiac death. as can be considered epidemic in industrialized nations. which is produced by narrowing of the vascular lumen (coronary heart disease. or Cooley's anemia. with decreased resistance). Because of its prevalence. in burns. Hemolytic anemia with extravascular hemolysis. hemorrhages.referring to the connective tissue components. It occurs in children and is characterized by  Progressive anemia with erythroblastemia.  Acute hemolytic anemia develops in poisoning with hemolytic poisons (mushrooms. The condition is characterized by presence of sickle-like erythrocytes revealed during crisis. or from weakening of the arterial wall leading to aneurysm. proliferation of vascular smooth muscle cells and fibroblasts.  Osteoporosis causing changes in the facial bones. And as a result of this erythrocytes are destructured 3) Defects of molecular structure of hemoglobin (hemoglobinopathies).  Increased hemolysis. Intrinsic defects (usually hereditary) are divided into three groups. Spherical-cell anemia is characterized by congenital spherocytosis (erythrocytes are small. cerebral infarction). The first sign of the disease is jaundice. transfusion of incompatible blood. The disease is characterized by intramural deposits of lipids. These abnormal erythrocytes are destroyed. DISEASES OF CARDIOVASCULAR SYSTEM ATHEROSCLEROSIS       Atherosclerosis is a multifactorial disease that affects the intima of elastic arteries. In some hereditary disorders.

Other risk factors. Stage of fatty stripes (lipoidois). The risk is correlated with elevated low-density lipoprotein (LDL). Stage of liposclerosis. stress. hyperglycemia. Many studies have demonstrated the specific effects of diet on lipid and lipoprotein levels. perhaps because HDL helps clear cholesterol from vessel lesion. and thrombus formation. Genetic factors (Heredity) Evidenced in cases with clearly defined abnormalities of lipid metabolism. Macrophages that have accumulated lipid in their cytoplasm appear histologically as csantomic or foam cells. formed from the catabolism of very-lowdensity lipoprotein (VLDL) to a cholesterol ester-protein core that carries some 70% of the total serum cholesterol. Lack of physical exercise. Risk is inversely related to the high-density lipoprotein (HDL) levels. Ruptured atheromas release thrombogenic material into the circulation. in premenopausal women then in men. macrophages and other cells.  Cigarette smoking. 2. Pathogenesis of AS has three stages: 1. Macrophages secrete growth factors and cytokines. hypertension and diabetes mellitus. Cytokines and growth factors also . their destruction occurs. Fatty stripes appear on intima due to its lipid infiltration. Possible explanations for the sex differences include levels of estrogenic hormones and higher levels of highdensity lipoprotein. and coffee consumption. lipoproteins and proteins fixation. Lipids impregnate intima and are accumulated in macrophages. and glycosaminoglycanes. The major background factors may be grouped into two main categories: I Endogenous (not modifiable) 1. physical activity. protein and fat. which is known to be antiatherogenic. familial hyper cholesteronemia. the destruction of endothelium and elastic and collagen fibers of intima's basal membrane. Other risk factors suggested being associated with AS obesity. platelets. It may be related to effects of the cigarette smoking on thrombosis or to increased concentration of carboxygemoglobin in the blood of smokers. Classification AS has the following microscopically stages (phases): 1. Elastic membranes become swollen. II Environmental (modifiable) 1.84  Background etiological factors influencing the rich of or susceptibility to atheroma are multiply and interrelated. nephrosis. Metabolic diseases. 3. and the intake of alcohol and concentrated sweets (anti-oxidants including red wine reduce the risk). the prevalence in men in the fourth decade is three times that in women. Macrophages also secrete growth factors that stimulate the proliferation of smooth muscle cells. Diet. including the amount of dietary cholesterol ingested. 4. myxedema. 2. causing thrombus for intimal ulceration. especially hyperlipoproteinemia. Endothelial injury is accompanied by the attachment of monocytes. 3. which recruit additional monocytes. Pre-lipid stage is characterized by mucoid swelling of intima and accumulation of plasma proteins. the total number of calories from carbohydrates. The component of cigarette smoking responsible for the acceleration of atherosclerotic events is not known. 2. Atheroma is specifically associated with high blood low-density lipoprotein levels (as well as total cholesterol levels). 2. These factors may act as increased blood lipids-cholesterol and lipoproteins. 3. There are diabetes mellitus. xanthomatosis. Especially in younger ages. Macrophages in the intima phagocytise lipid and transform into foam cells. Apparent genetic roles in familial predisposition to AS may be related to genetic effects on other risk factors. Sex Atherosclerotic coronary heart disease is predominantly a disease of men.  Hypertension.

Outcome is atherosclerotic nephro-cirrhosis. which replaces the normal intimal cells. atheromas typically covered with an intimal fibrous cap. Aneurysms These are localized abnormal dilatations of vascular wall. Atherosclerosis of renal arteries leads to atrophy of parenchyma. 5. 2. cholesterol is released into interstitial spaces. atheroma must be very severe before chronic ischemia with intermittent claudication/or gangrene develops. Morbidity and mortality are secondary to  Rupture. Macroscopically dense. The calcification of vessels leads to hardening of arteries.  Occlusion of proximate vessels by either extrinsic pressure or superimposed thrombosis. Lipid accumulates not only in macrophages but also in smooth muscle cells. Clinical-morphological appearances 1. 6. The complicated lesion is the most common type of atherosclerotic lesion that produces significant circulatory change and clinical disease. Atheromas weaken the arteries and predispose to formation of aneurysm. Most common (and significant) are aortic aneurysms. Atherosclerosis of carotides leads to acute local ischemia and cerebral softening (infarction). Dystrophy and atrophy of the brain cortex may develop as result of the long-term ischemia. Atherosclerosis of arteries of cerebrum. surrounded by collagen. aneurysms are classified as follows: . cystic medial necrosis (the two most common causes). Stage of atherocalcinosis is characterized by deposition of calcium in ulcerative plaque. In the areas of lipidosis a young connective tissue grows and forms a fibrous cap. Development of aortal aneurysm is possible. On the luminal side. General chronic ischemia of brain leads to senile dementia. white formations are observed there.  Etiologies of aneurysms include atherosclerosis. Cholesterol clefts are recognized by their typical needleshaped appearance. thromboembolism and embolism to legs. 4. leading to the gangrene. syphilis. Atheromas consist of amorphous lipid-rich material and are soft. The thrombosis with gangrene of leg is possible. Atherosclerosis of arteries of extremities. 6. consisting of fibroblasts. Stage of ulceration is characterized by the break of the fibrous cap cover and forming of ulcer with small hemorrhage into plaque. Atherosclerosis of aorta . Morphologically. The results are ischemic infarctions of brain. Collateral circulation is usually good. ulceration. 5. oval. Complicated plaques develop from preexisting fibrous plaques as a result of one of a combination of several pathologic changes that include calcification. From dead and dying cells. It‟s possible the development of thrombosis.85 stimulate the proliferation of smooth muscle cells and their ingrowth into the intima from the tunica media.the most common form. Stage of atheromatosis is characterized by necrosis of the central part of fibrous cap with forming of amorphous substance (atheromatouse detritis). very often this process is located in femoral arteries. Dense and fragile cap is formed due to the cap of connective tissue infiltration with calcium. trauma. and infections (mycotic aneurysms).  Embolism from mural thrombosis.  Impingement on adjacent structures. May be causes acute infarction. 3. Atherosclerosis of arteries of an intestine is complicated by the thrombosis. less often the haemorrhage in brain occurs. Usually it is not complicated by the thrombosis. 4. or infarction. thrombosis and hemorrhage. Atherosclerosis of coronary arteries of heart lead to ischemic heart disease (IHD). congenital defects.

3. Benign hypertension is moderate elevation of blood pressure and the rise is slow as the years pass. Small muscular arteries show segmental dilatation as a result of necrosis of smooth muscle cells. both have an increased risk of serious complications. . 2. Increased release of renin and generation of angiotensin.  Tumor of adrenal medulla (pheochromocytoma) – catecholamine excess. hypertension disease would be cure. hemorrhages and hypertensive encephalopathy. 1. which yields the so-called onionskin appearance. depending on the size of the vessels affected. Saccular aneurysm. an increase in the structural mass of the vessel wall. The combination of cell necrosis and deposition of plasma proteins in the vessel wall is termed fibrinoid necrosis. of both systolic . Arterial hypertension is defined clinically as borderline when it riches 140/90 mm Hg and hypertensive when 165/95 mm Hg. All the above mechanisms are essentially vaso-constrictor. Spherical dilatation due to congenital wall weakness. Gradual lumen dilatation generating a spindleshaped lesion up to 20 cm in diameter. 2. Taken together. The period of acute injury is rapidly followed by smooth muscle proliferation and a striking increase in the number of layers of smooth muscle cells. but diastolic hypertension is more dangerous. In 90-95% of all cases of hypertension. Examples:  Kidney diseases.  Hypertension occurs in toxemia of pregnancy.and diastolic pressure (diastolic hypertension). Hypertension is classified into two types: 1. no cause can been established – such cases are called essential or idiopathic or primary. According to the clinical course. In only 5-10% of all cases of hypertension is any disease. the resistance vessels that control the flow of blood through the capillary bed. typically in the circle of Willis. Large spherical dilatation up to 20cm in diameter. which may be associated with disturbance of these mechanisms detectable – such cases are secondary hypertension. The morphologic changes associated with moderate elevations of blood pressure are too subtle to be detected by simple histological studies. often at least partially filled with thrombus. generally less than 1. The lumen may be restricted by active contraction of the vessel wall. Increased sympathetic tone.86     Berry aneurysm. If these causes of secondary hypertension were eliminated. and to the full length of the aorta. and finally. or both. A postulated excessive responsiveness to the other factors. Malignant hypertension is marked and rapid increase of blood pressure to 200/140 mm Hg or more and the patients have papilledema. Morphology      It is important to realize that the central lesion in most cases of hypertension is a decrease in the size of the lumen in small muscular arteries and arterioles. 5.  This hypertension comprises 5-10% causes of disease. usually in the aortic arch. hypertension is the most common serious chronic disease. 4. and dissects the layers-typically between the middle and outer thirds of the media. About 90% of patients of hypertension have benign disease. Blood enters the arterial wall through a tear. affecting about a half of the population over 50 years of age. AS is the most common cause. HYPERTENSION In medically advanced countries. (systolic hypertension) or elevation. Dissecting aneurysm. both types of hypertension may be benign or malignant. The possible roles of vaso-dilator mechanisms – for example the effect of nitric oxide on vascular smooth muscle – are being currently researched. these changes are labeled malignant arteriosclerosis or malignant arteriolosclerosis. Fusiform (cylindroid) aneurysm. The increased peripheral resistance resulting in sustained hypertension may arise from: 1. The presence of vasoconstrictive substances in the circulation.5 cm in diameter. 2. The etiology is usually atherosclerosis. There is elevation of systolic pressure alone.  Hyperfunction of adrenal cortex (Cushing „s syndrome – corticosteroid excess). Increased sodium load and extracellular fluid load.

 Macroscopically. 2. thrombosis. These changes develop slowly. Within 2-3 days.  Microscopically. It is usually the result of fragmentation of occlusive arterial emboli or venous thrombosis. there is focal softening.  Cerebral infarction is a localized area of tissue necrosis caused by local vascular occlusion. The area supplied by distal branches of the cerebral arteries suffers from the most severe ischemic damage and may develop border zone or watershed infarcts in the adjacent zones between the territories supplied by major arteries. the papillary muscles are rounded and prominent. the nerve cells die and disappear and are replaced by reactive fibrillary glia. But when decompensation and cardiac failure develop. Cardiac form     Hypertensive heart disease or hypertensive cardiomyopathy is the disease of the heart resulting from systemic hypertension of prolonged duration and manifesting by left ventricular hypertrophy. The stage of secondary changes of organs is developed in connection with changes of arteries and insufficiency of the intraorganic blood circulation. an anemic infarct becomes evident 6 . Heart is called “cor bovinum”. plaques are more often circular.  Macroscopically.  A hemorrhagic infarct is red and superficially resembles a hematoma. Often hypertension predisposes to atherosclerosis. It is characterized first of all as impairment of cerebral blood circulation. At this stage the hypertrophy of the left ventricle of heart begins. 2. fibrinoid necrosis) and causing infarctions and hemorrhages ( it’s characteristic of malignant hypertension). muscular-elastic and muscular arteries walls undergo elastofibrosis and atherosclerosis. Arteriolar walls permeability is increased. especially of the left ventricle. Elastofibrosis is characterized by a hyperplasia and breaking of internal elastic membrane and spreading of connective tissue. the infarct undergoes softening and disintegration. . The arterial changes and vascular complications increase with the severity and duration of the hypertension.87 Clinical-morphological stages 1. sex (females tolerate hypertension better). A stage of general changes of arteries begins as arterial pressure increases. that cause acute mechanical stenosis of the vessel. and associated diseases. The affected area is soft and swollen and there is blurry of junction between gray and white matter. The main clinical-morphological forms of essential hypertension 1. spasm of arterioles. quickly (spasm. but are modified by genetic factors. Cerebral form (Cerebrovascular diseases. Atherosclerotic changes in case of hypertension are more extensive. there is eccentric hypertrophy (myogenic dilation) with thinning of the ventricular wall and dilation of the left ventricular and atrial cavities. environmental factors. 3.  Cerebral infarction may be anemic or hemorrhagic. Weight of heart reaches 1 kg. There may be dilatation and hypertrophy of right heart as well. the most significant finding is marked hypertrophy of the heart.12 hours after its occurrence. Macroscopically. thickness of left ventricle walls is up to 3 cm. the process reaches small-sized arteries of muscular type. that results in atrophy of parenchyma and sclerosis (it’s characteristic of benign hypertension).  The pathologic appearance of the brain in hypoxic encephalopathy varies depending on the duration and severity of hypoxic episode and the length of survival. Elastic. and the cardiac chamber is small (concentric hypertrophy). This hypertension can result in two main types of parenchymal diseases of the brain: 1) Ischemic brain damage (hypoxic encephalopathy and cerebral infarction). it results in plasmatic impregnation and hyalinosis. Subclinical stage occurs by hypertrophy of muscular layer and elastic structures of arterioles and small-sized arteries. 2) Intracranial hemorrhage (intracerebral and subarachnoid hemorrhage).

anoxia) but also reduced availability of nutrient substrates and inadequate removal of metabolites. 8. Smoking. mostly from hemorrhage into the ventricles. these include glomerular shrinkage.88     Hemorrhage into the brain of patient with hypertension is intracerebral hemorrhage. Ischemia comprises not only insufficiency of oxygen (hypoxia. Hyperlipidemia. Clinical features are variable. The cardiac complications therefore account for 36% of the death. 5. which is usually of hypertensive origin due to rupture of microaneurysm. dizziness. Impairments of tolerance to carbohydrates. Diathesis. Sex-binded. and palpitation. In case of malignant hypertension can develop as hypertonic crisis . thrombosis or thromboembolism of coronary arteries of heart. 2. Pathogenic factors (factors of risk) are: 1. Kidneys have a term “primary shrunken kidneys”. Microscopically. Causes unrelated to hypertension. 6. 4. both kidneys are affected equally and are reduced in size and weight. periglomerular fibrosis. .acute increase of arterial pressure in communication (connection) with spasm of arterioles. Macroscopically. The common sites of hypertensive intracerebral hemorrhage are the region of the basal ganglia. Steatosis. ISCHEMIC HEART DISEASE Ischemic heart disease (IHD) is the generic designation for a group of closely related syndromes resulting from ischemia – an imbalance between the supply and demand of the heart for oxygenated blood. There is variable degree of atrophy of parenchyma. Because coronary artery narrowing or obstruction owing to atherosclerosis underlies myocardial ischemia in the vast majority of cases. About 40% of patients die during the first 3-4 days of hemorrhage. Morphological appearance of hypertonic crisis: plasmatic impregnation or fibrinoid necrosis of arteriolar walls. deposition of collagen in Bowman's space. Direct reasons of development of the myocardial infarctions are spasms of vessels. Genetic predisposition. there are primary diffuse vascular changes. 3. Arterial hypertension. 9. which produce parenchymal changes and secondary as a result of ischemia. The capsule is connected densely to the cortical surface. The surface of the kidney is finely granular and shows V-shaped areas of scarring. Patients can be paralyzed. Cerebrovascular accidents. 3. Renal failure and uremia may occur. Renal form         Renal form is characterized by chronic arteriolo-sclerotic nephrosclerosis. Coronary artery disease. The outcome of intracerebral hemorrhage is cyst formation. 7. The etiology and pathogenesis Etiology of IHD is identical to the one of atherosclerosis and hypertension. IHD is often termed coronary artery disease (CAD) or coronary heart disease (CHD). Uremia. Hypodynamia. elevation of the blood pressure with headache. The cut surface shows firm kidney and narrowed cortex. often weighting about 6 gm. medulla and cerebellum cortex. The causes of death among hypertensive patients are the following:      Congestive heart failure.

but this is observed rarely. At least 90% of transmural acute MI are caused by an occlusive intracoronary thrombus overlying an ulcerated or fissured stenotic plaque. and tends to be of prolonged duration. emotional excitement. According to the degree of thickness of the ventricular wall: . 3. Pathogenesis.lateral wall of left ventricle.interior/posterior wall of left ventricle. 2. Angina pectoris.the infarctions of the anterior wall of left ventricle near apex or anterior two-thirds of interventricle septum. or knife-like) caused by transient (15 sec. Prinzmetal’s variant refers to a pattern of episodic angina that occurs at rest and has been documented to be due to coronary artery spasm. Classification of Myocardial infarction I. right ventricle. Sudden cardiac death. The function becomes strikingly abnormal within 1 min after ischemia. posterior right ventricular free wall in some cases. 3) Stenosis of the left circumflex coronary artery is seen least frequently (15-20%) . is overwhelmingly the most important form of IHD in industrial nations. According to the anatomic region of the left ventricle: anterior. posterior.) myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction. choking. four ischemic syndromes may result: 1. or any other cause of increased cardiac workload. Stable (typical) angina pectoris appears to be reduction of coronary perfusion to a critical level by chronic stenosing coronary atherosclerosis. Unstable angina is induced by fissuring. Occlusion of a major coronary artery results in ischemia throughout the anatomic region supplied by that artery. Chronic ischemic heart disease. ulceration. often occurs at rest. but myocardial coagulation necrosis occurs only after 20 to 40 min of severe ischemia. or rupture of an atherosclerotic plaque with superimposed partial thrombosis and possibly embolization or vasospasm. is precipitated with progressively less effort. Acute Ischemic Heart Disease (AIHD) Angina pectoris It is a symptom complex of IHD characterized by paroxysmal attacks of substernal or pericordial chest discomfort (variously described as constricting. such as that produced by physical activity. and right atrium. 3. septal and circumferential. posterior one-third of interventricular septum. most pronounced in the subendocardium.89 Depending on the rate of development and ultimate of the arterial narrowing and the myocardial response. According to localization: left ventricle. squeezing. left atrium. III. Besides it may be located in other parts of heart. 2. differentiated on the basis of the provocation and severity of the pain: 1. The region of infarction depends upon the area of obstructed blood supply by one or more of the three coronary arterial trunks: 1) Stenosis of the left anterior descending coronary artery is the most common (40-50%) . Infarctions are most frequently located in the left ventricle. Acute myocardial infarction (MI) Acute myocardial infarction also known as “heart attack”. II. to 15 min. 2) Stenosis of the right coronary artery is the next most frequent (30-40%) . Unstable angina refers to a pattern of pain that occurs with progressively increasing frequency. 4. This syndrome is sometimes referred to as preinfarction or acute coronary insufficiency. There are three somewhat distinctive patterns of angina pectoris. lateral. this renders the heart vulnerable to further ischemia whenever there is increased demand. Myocardial infarction.

shrunken fibrous scar. Subendocardial or lamina constitutes an area of ischemic necrosis limited to the inner onethird or at most one-half of the ventricular walls. ultimately generating a dens fibrous scar. 1. Acute myocardial infarction develops in the first time (during 8 weeks from beginning of ischemic necrosis). and myocytes become wavy and buckled. hard. . It is thin. Repeated myocardial infarction develops after 8 weeks of acute infarction. According to the duration of infarctions: 1. Subepicardial is rare infarction. decreased blood supply. Full-thickness or transmural.  By 18-24 hours infracted tissue is pale to cyanotic. typical coagulative necrosis is not yet evident. The consistency of infarct in this period is soft. 3.  Fibrous scar is well established by 6 weeks. as well as the reserve of functional myocardium. Morphology  The macroscopic and microscopic changes in the myocardial infarction correspond to the age of the infarct. lymphocytes and plasma cells are seen.  A circumferential rim of hyperemic granulation tissue that progressively expends may be seen by 7 to10 days. Left ventricular congestive failure and mild-to-severe pulmonary edema (60%).  Between 3 and 7 days dead myocytes begin to disintegrate and are resorbed by macrophages and enzyme proteolysis. 6.  At 7 to 10 days granulation tissue appears and progressively replaces necrotic tissue.  In 12 to 72 hours a neutrophilic infiltrate into necrotic tissue with progressive evolution of characteristic eosinophilic coagulative necrosis can occurs. At this stage. border-zone viable cells show fine lipid droplets and large cytoplasmic vacuoles called vacuolar degeneration or myocytolysis. 3. In addition. gray-white. which is characterized by pneumonitis.90 1.  In fourth to sixth week increased fibrous tissue. 5. It is called reactive pericarditis. 4. fewer pigmented macrophages. Mural thrombosis and thromboembolism from intracardiac thrombi and thrombosis in the leg veins is observed in 15-45% cases of acute myocardial infarction. Microscopically. there is intercellular edema.  In 6-12 hours the lesion may have a slight pallor but may be inapparent. Fibrinous pericarditis appears on the second day of myocardial infarction. During the first weak the heart rupture may develop. endocarditis with thrombus and fibrinous pericarditis can develop.4% of patients who suffered from acute myocardial infarction develop postmyocardial infarction syndrome. 3. Arrhythmias are the most common form of complication in acute myocardial infarction (75 to 95%). Complications of infarction Complications of infarction depend on the size and location of the necrosis. in which the ischemic necrosis involves the full or nearly full thickness of the ventrical wall in the distribution of a single coronary artery. 2.  During first week the lesion becomes progressively more sharply defined. 7. About 3 . Cardiogenic shock (10%). Recurring (recidivic) myocardial infarction develops during 8 weeks of acute infarction. 2. often extending laterally beyond the perfusion territory of a single coronary artery. Rupture of the septum produces a left-to right shunt with right heart volume overload. which is often fatal. As a result the rupture of cardiac wall. however. In region of it fibrinous inflammation of pericardium develops. the color of infarction is charged from cyanotic red to bright yellow or yellow-green. 2. within one hour of ischemic injury. IV. changes in as early as 3 to 6 hours may be accentuated by use histochemical techniques. This is attributable to stretching of noncontractile dead fibers by adjacent viable contracting myocytes. Rupture of the free wall causes pericardial hemorrhage and tamponade.

or hypertrophic cardiomyopathy. . Dressler‟s syndrome. Marked coronary atherosclerosis with critical (greater than 75%) stenosis involving more than one of the three major vessels is present in 80 to 90 % of victims. In the vast majority of cases in adults SCD is a complication and often the first clinical manifestation of IHD. acute ischemic injury. Cardiogenic shock. so as to prevent or postpone heart failure. Cardiac aneurysm often occurs in the left ventricle. Microscopically: diffuse or local perivascular and interstitial fibrosis. In some cases the hypertrophy of adjacent myocytes occurs. mitral valve prolapse. Sudden cardiac death (SCD)    Defined as unexpected death from cardiac causes early after or without the onset of symptoms. Morphology. it impairs the function of the heart and is the site for mural thrombi. Infrequently. Causes: 1. petechias. or both.91 8. sometimes fatal. Macroscopically: on section white foci of sclerosis or brown coloration of the heart.  It appears that stretching of myocardial fibers in response to stress induces the cells to increase in length. spleen) and development of the “nutmeg” liver. or electrical instability due to electrolyte imbalance. Most cases of CIHD constitute simply postinfarctional cardiac decompensation or slowly ischemic myocyte degeneration. indurations of organs (lungs. Compensatory hypertrophy  Hypertrophy of the heart is defined as an increase in size and weight of the myocardium. The ultimate mechanism of death is almost always a lethal arrhythmia. moderate to severe multivessel stenosing coronary atherosclerosis and sometimes total occlusions resulting from organized thrombi. as a consequence of ischemic myocardial damage. 2. Cardiosclerosis leads to chronic cardiac insufficiency. The main causes of death in this case are complications 1. Cardiac hypertrophy and dilation The heart may undergo compensatory enlargement in the form of hypertrophy.g. It is immunocomplexis reaction to decomposition‟s products of the necrotic tissue with formation pericarditis and right-side pleurisy. only 10 to 20% of cases are of nonatherosclerotic origin. The pericardial surface of the heart in CIHD may have adhesions as the result of healing of pericarditis also associated with post myocardial infarctions. 9. hypertrophy of left ventricle or. Chronic Ischemic Heart Disease (CIHD)          The designation of CIHD is used for the heart of patients often but not exclusively elderly. some reduction in heart size. dilation. valvular incompetence) results in hypertrophy with dilatation of the affected chamber due to regurgitation of the blood through incompetent valve. Acute cardiac insufficiency. 4. which is characterized by congestion: edema. kidneys. who individuously develop congestive heart failure (CHF). The atria may also undergo compensatory changes due lo increased workload. presumably triggered by previous conduction system scarring. Due to postinfarctional cardiosclerosis the chronic heart’s aneurysm may develops. in contrary. in others cases myocytic atrophy with perinuclear deposition of lipofuscin appears. Cardiosclerosis can be local postinfarctional and diffuse atherosclerotic. 3. It generally results from increased pressure load while creased volume load (e. cyanosis. The common causes of left ventricular hypertrophy are: a) Systemic hypertension. Thromboembolism. Tamponade of heart. it is a consequence of myocarditis. Left ventricular hypertrophy. Patients may die due to cardiacdecompensation or thromboembolism. The elongated fibers receive better nutrition and thus increase in size.

cellular reactions. Right ventricular hypertrophy. g) Conditions with increased cardiac output: thyrotoxicosis. thyrotoxicosis. . b) Tricuspid insufficiency. Presence of hypersensitivity of immediate type with development of exudative – necrotic reactions and hypersensitivity of delayed type with formation cellular infiltration. while in eccentric hypertrophy the lumen is dilated. rheumatic arthritis has less severe course in the residents of Africa than in those of Europe. tricuspid and/or pulmonary insufficiency in right ventricular dilatation).  Causes: a) Valvular insufficiency (mitral and/or aortic insufficiency in left ventricular dilatation. Lupus erythematosus is more frequent in Europian countries and USA than in Great Britain. In concentric hypertrophy. RHEUMATIC DISEASES    Rheumatic diseases are group of collagen or systemic connective tissue diseases including rheumatic fever.g. Most of the causes of right ventricular hypertrophy are due to pulmonary arterial hypertension.  Microscopically. In pure hypertrophy.  Hypertrophy of the myocardium without dilatation is referred to as concentric. The weight of the heart is increased above the normal. Systemic progressive disorganization of connective tissue includes mucoid swelling. the thickness of the left ventricular wall above 15 mm is indicative of significant hypertrophy. hypertrophy of the heart is accompanied by cardiac dilation. the lumen of the chamber is smaller than usual. injury of microcirculation with following systemic progressive disorganization of connective tissue are main links of pathogenesis of rheumatic diseases. development of autoimmune reactions. d) Chronic lung diseases: chronic emphysema. Compensatory dilation. pulmonary vascular diseases. while in hypertrophy with dilatation these are flattened. anemia. and when associated with dilatation is called eccentric. the papillary muscles and trabeculae cameae are rounded and enlarged. e) Occlusive coronary artery disease. They are characterized by affect of collagen or connective tissue due to disturbances of immune homeostasis. pneumoconiosis. sclerosis. Disturbances of immune homeostasis. dermatomyositis and polyarteriitis nodosa. c) Myocardial diseases: cardiomyopathies. f) Congenital anomalies like septal defects and patent ductus arteriosus. Quite often. Combination of different phases of connective tissue disorganization. and Bechterew‟s disease. etc. Chronic recurrent diseases with alternation of periods of exacerbation and remission Genetic and environmental factors are important for development of these diseases. General characteristic of rheumatic diseases       Presence of chronic infectious focus. e) Left ventricular hypertrophy. Thus. c) Mitral stenosis and/or insufficiency. often over 500 gm. and arteriovenous fistulae. formation of the toxic immune complexes and sensibilizated cells. d) Systemic hypertension. Presence of early systemic changes of microcirculation. arteriovenous shunt. There may be multiple minute foci of degenerative changes and necrosis in the hypertrophied myocardium. 2. bronchiectasis. b) Conditions with high cardiac output e. c) Mitral insufficiency. These are: a) Pulmonary stenosis and insufficiency.  Macroscopically. which indicates the chronic character of the diseases.92 b) Aortic stenosis and insufficiency. myocarditis. there is increase in size of individual muscle fibres. fibrinoid changes. scleroderma. rheumatoid arthritis. d) Coarctation of the aorta. systemic lupus erythematosus.

93 RHEUMATIC FEVER (RF) and RHEUMATIC HEART DISEASE (RHD)       RF is an acute. Erythema marginatum. 3. Typically. or pericarditis. macular lesions with erythematous rims and central clearing. 2. there is endothelium proliferation followed by desquamation. being secondary usually to the myocarditis. and disintegration. the principal lesions being in the connective tissues throughout the body. 4. rheumatic pneumonia is visceral changes. RF has four stages. Carditis. arteriosclerosis. capillarosclerosis). the myocarditis and arthritis are transient and largely resolve. when the first bout of RF is severe. It may be myo-. Arthralgia. so-called rheumatic endotheliosis. Also may develop:  Rheumatic glomerulonephritis. are altered considerably and take on a deeply eosinophilic appearance resembling fibrin. 5. In the early phase of development of the lesions. The affected areas. involuntary. especially in the heart.  Fibrinoid changes. excluding the initial infection (tonsillitis. giant Aschoff bodies are noted. The various manifestations of the disease in the heart and other regions of the body. nasopharyngitis). 2. that is. and subsequently they undergo swelling. The collagen fibers are pushed apart by the accumulating of basophilic ground substance. Migratory large joint polyarthritis. Pathogenesis and Morphology of RF A widely accepted concept of the nature of RF is that it is one of the so-called immune disorders of connective tissue. thus. A neurologic disorder with rapid. There is specific skin “rush”. or with recurrent attacks. Leukocytosis. The early exudative and degenerative features are followed by proliferation. plasma cells.  Mucoid swelling. 4. inflammatory.  Rheumatic vasculitis with fibrinoid changes of the walls. but the valvular involement may lead to deformed. The disease results in vascular sclerosis (arteriolosclerosis. Histologically. Seen in children more often than adults. typically in a bathing suit distribution. Vascular permeability increases sharply. but it is not serious import to the patient unless it involves the heart. the change is referred to as fibrinoid degeneration or necrosis. are not the result of a direct infection.  Hyperplasia of lymphatic tissue. “rheumatic fever licks the joints but bits the heart”. . purposeless movements. Rheumatic Fever is thus a disease that involves many regions of the body. Death is rare during acute RF. recurrent disease mainly of children (ages 5 to 15) that typically occurs 1 to 5 weeks after a group A streptococcal infection (usually sore throat). but microbe initiated autoimmune reactivity is not ruled out. 3. It has been said. endo-. an infiltration by lymphocytes.  Cellular reactions. The most distinctive proliferative lesion is the granulematous phase of the Aschoff body. including collagen fibers and the ground substance. Diagnosis rests on the clinical history and the presence of five major (Jones) criteria: 1. Seen in children more often than adults. Acute RF occurs after the infection with beta-hemolytic streptococci group A. Longer PR interval in the ECG. Minor criteria: 1. Most evidence suggests is secondary to host antistreptococcal antibodies that are crossreactive to cardiac antigens. fragmentation. Sydenhams chorea. Subcutaneos nodules. histiocytes. edema of the connective tissues is associated with an increase of mucopolysaccharide. and fibroblasts. Chronic RHD is more likely to occur when the first attack is in early childhood. fraying. scarred valves with permanent dysfunction (chronic RHD) and subsequent CHF. marked plasmatization is observed in the immune system. In the capillaries. Fever.

this nonspecific inflammatory reaction may be all that occurs. there is endocarditis. macrophages and a few plasma cells. It may lead to thickening. therefore deformation and ankylosis is absent. Lesions may also be present on the chordae tendineae. In the active acute stage of the disease the valve leaflets or cusps are thickened and lose their transparency. or healed) phase. Edema with swelling of the leaflet. The collagenous fibers fuse to form dense collagenous bindles. . These constitute foci of fibrinoid necrosis. Anitschkow cells are mononuclear cells. or alterative) phase. humeral. mainly along the line of closure of the cusps. Abrikosov. hip joint. pericarditis. Their nuclei are large and vesicular and contain a prominent central chromatin mass that longitudinal section is serrated (caterpillar-like). 3. In cross section a halo is observed about the chromatin bar so that the nucleus has an “owl-eye” appearance. the healing phase is reached. In the synovial membrane the mucoid swelling develops. The damage of the brain is connected with rheumatic vasculitis. which is evident during the fourth to the thirteenth week of the disease.I. Diffuse or valvulitis. Early (exudative. and blunting of valvular leaflets. If these changes are clearly marked. In the intermediate phase. This is followed by the appearance of characteristic wartlike nodules (verrucae) ranging from 1 to 3 mm in diameter. Polyarthritic form occurs migratory large joint polyarthritis (knee. Pathognomonic focal inflammatory nodules called Aschoff bodies are the most characteristic in the heart. and pericarditis. however. valvular endocarditis is classified as follows: 1. cubital. frequently perivascularly. fibrous. myocarditis. degenerative. They have a moderate amount of faintly stained cytoplasm with vaguely defined borders. Microscopically: fibrinoid necrosis with thrombotic masses. Acute verrucous endocarditis. Intermediate (proliferative or granulematous) phase. ankle-joint). Endocarditis (valvulitis)  The most prominent changes develop in mitral and aortic valves. initially surrounded by lymphocytes. and are rarely on the papillary muscles of the left ventricle. particularly at their attachment to the leaflets. Usually. but similar lesions may occur elsewhere. healing. 2. The early phase of the life cycle of the Aschoff body occur up to the fourth week of acute RF. brain destruction and hemorrhages occur in the brain. Cardiovascular form occurs endocarditis. cellular proliferation is the dominant feature. It is characterized by serous or serous-fibrinous inflammation. 2.  According to A. Aschoff bodies or diffuse inflammatory cellular infiltration are slowly replaced by fibrous scar mainly about the vessels. characterized by regression and fibrosis of the nodule. myocarditis. they may cause chorea minor (in children). and an infiltration by lymphocytes and occasionally by neutrophils are seen. Clinical-anatomical forms of Rheumatic Fever: 1. 2. with alteration of collagen and the fibrinoid change near the surface of the valve and with surface deposition of fibrin from the blood in the ventricular cavity. Late (senescent. Nervous cells degeneration. Articular cartilage is safe.94  Sclerosis. In 3 to 4 months. an increased number of capillaries. Distinctive plump histiocytes (Aschoff or Anitschkow cells). that is. Cerebral form occurs chorea. Cardiovascular form The cardiac involvement in RF is that of a pancarditis. In some instances. 3. 4. some of which are multinucleated (Aschoff multinucleated giant cells with abundant basophilic cytoplasm). shortening. resulting in small scars between the muscle bundles. there is also an increase in acid mucopolysaccharide. Plasma cells and fibroblasts may be present. appear in periphery of nodules. Nodular (nodules around vessels) form occurs deposition of giant Aschoff bodies under skin and may develop perivascular sclerosis. Three phases or stages in the development of the Aschoff body are recognized: 1.

e) Frequently. especially mitral or aortic. thickening. When mitral insufficiency is the main alteration. Mitral insufficiency and stenosis are commonly combined. d) Thickening. the chordae tendineae.95 3. Contraction of scar tissue takes place. and calcification of the mitral cusps and ring frequently is present to a greater or lesser degree. Fibrous adhesion at the comissures may be slight or extensive. especially toward the closing edges. b) Dilatation and hypertrophy of the left atrium. the effects are the follows: a) Dilatation and hypertrophy of the left ventricle. namely. 4. with contributes to the rigidity of the valve. b) Organization of the vegetations. As the entire valve becomes more rigid it takes on appearance of a fixed diaphragm with a narrow oval or curved opening. Mitral stenosis is the result of rheumatic endocarditis or bacterial endocarditis. so-called purse-string puckering. thickened tissue. The following changes take place: a) Fibroblastic proliferation and collagen formation throughout the valve with scarring. and rigidity of the leaflets. which occasionally appears as a huge saclike structure (so-called giant left atrium). Ulceration of the thickest part of deformed valve is a common occurrence. the valve leaflets become more rigid. When the valves are less extensively involved and the bases of the leaflets are still somewhat pliable.   The result is deformity of one or more valves. the papillary muscles. c) Effects on the right side of the heart as in mitral stenosis after left-sided failure. Fibroblastic or healing of the rheumatic valvulitis. d) Hypertrophy and dilatation of the right ventricle as a result of pulmonary hypertension e) Dilatation of the right atrium as a right-sided heart failure develops. b) Endocardial fibrous thickening of the left atrium. particularly in the region of the commisures. a “buttonhole” or “fish-mouth” orifice. . Relapsing verrucous endocarditis. with greater thickening along the line of closure. which result in heart failure because of the increased work of the heart caused by the valvular stenosis of insufficiency. often greater than in mitral stenosis. and the left ventricle. the functionally important lesions are those of the valves. Valvular insufficiency may result because of retraction of the scarred leaflets in the vertical direction leading to shortening of the cusps. shortening. c) Adhesions between the lateral portions of the cusps. The orifice becomes considerably narrowed. c) Pronounced chronic passive congestion of the lungs. calcification. Changing hemodynamic conditions may dramatically improve or worsen the degree of mitral regurgitation. and fusion of the chordae tendineae. Proper closure of the mitral valve depends not only on the mitral valve leaflets by themselves but also on several additional functional components of the mitral valve apparatus. the narrowed opening is surrounded but puckered. The effects of mitral stenosis develop as a consequence of obstruction to the outflow of blood from the left atrium and include the following: a) Dilatation and hypertrophy of the left atrium. Mitral insufficiency       The pathophysiology of mitral regurgitation is complex. eventual pulmonary-arteriolar thickening. In the chronic or recurrent condition. The gross appearance of the stenotic valve varies greatly according to the degree of involvement. Mitral stenosis           The most characteristic type of deformity causes mitral stenosis. The leaflets are fibrotic and thickened.

plasma cells. lungs. be attributable to various conditions such as pneumonia. In the later stages of the disease may diffuse small-focal cardiosclerosis. Thickening. infective endocarditis. including foci of perivascular interstitial fibrosis and vascularization of the valves. atrophic left ventricle caused by reduced inflow of blood. and to a “chronic adhesive pericarditis”. in prolonged mitral stenosis. spleen. and the Aschoff bodies are converted into small scars. Chronic adhesive pericarditis. shortening. Atrial fibrillation contributes to blood stasis and predisposes to development of thrombosis. Nonspecific exudative interstitial myocarditis. thus the designation of “shaggy” heart. with lesions of the large joints appearing later in the course of the disease. The chief causes of death in RF patients are cardiac failure.96  f) A normal-sized left ventricle or. more significantly. 4. Subsequently. This may lead to fibrous thickening and adhesions of the visceral and parietal layers. and fibrinous pericarditis is a prominent part of the picture of acute rheumatic heart disease. or “cor villosum”. lymph nodes. fibrin is seen as a shaggy layer on the surface of the epicardium and an infiltrate of lymphocytes. Myocarditis Rheumatic myocarditis is characterized by the presence of 1. and other organs can be affected. There is gradual subsidence of the inflammatory reaction. it is usually a little physiologic significance and does not usually affect the clinical course of the patient. 6. with possible hypertrophy of this ventricle if mitral insufficiency or aortic stenosis is present. to partial or complete obliteration of the pericardial cavity. RHEUMATOID ARTHRITIS Rheumatoid arthritis (RA) is a chronic progressive inflammatory arthritis of unknown origin involving multiple joints and characterized by disorganization of connective tissue of the synovial membrane and articular cartilarge and development of their deformation. and embolism.  RA is basically a severe form of chronic synovitis that can lead to destruction and ankylosis of affected joints. 5. especially in the left atrial appendage. Granulematous myocarditis. sceletal muscle. Postmorten diagnosis of old rheumatic disease is based on the following marks: 1. especially circumscribed obliteration of the cardiac sac nears the apex. It is characterized by diffuse or focal lymphohistiocytic infiltration and vasculitis. systemic embolism may result. RA is likely an autoimmune disease. One of the complications that may occur in mitral stenosis and the consequent atrial dilatation is atrial fibrillation. however. . 2. and adhesions of the chordal tendineae. heart. especially at the line of closure. It is characterized by the presence of specific Aschoff bodies. Although pericarditis may be the most prominent gross manifestation of the acute disease. especially aortic or mitral stenosis of insufficiency and. involvement of both the aortic and mitral valves. Death may. 2. organization of the fibrin by vascularized connective tissue may be observed. Fibrous thickening of the valve leaflets. Microscopic changes. eyes. 3.  Although the skin. histiosytes. 3. Valvular deformities. The small joints of hands and feet are usually the first and most common to be involved. and occasionally neutrophils are present. central and peripheral nervous system. Parenchymal damage may lead to acute cardiac insufficiency and to death in early stages of disease or to chronic ischemic heart disease. Pericarditis      The tendency to affect serous membranes is one of the distinctive features of RF. The exudate varies from a thin film of fibrin to a shaggy coat with adhesions between the layers of the pericardium. Microscopically.

 Not infrequently. composed of fibrin. Pathogenesis of RA      Rheumatoid disease is often accompanied by characteristic immunoglobulin (often IgM). these deposits are composed of fibrin and small amounts of gamma globulin and complement components. with complete elimination of the joint. First stage  Acute inflammatory reaction with development of edema.  Granulation tissue composed of synovial fibroblasts and capillaries causes grossly recognizable villous thickening of the synovium. which eventually fills the joint space.  Release of destructive enzymes (proteases and collagenases) and cytokines (particularly IL1) and pannus formation destroy cartilage. and macrophages. Stages of synovitis: 1. in affected person serum. 2.  This exuberant synovium is known as pannus. synovial lining cells. 3. mast cells. encroaching upon the articular surfaces. Other autoantibodies are also found in RA.  In some of these lining cells as well as lymphocytes and plasma cells of the synovium and in leukocytes of the synovial fluid occur. an immune complex binds complement and forms the intraarticular chemotactic factors C3a and C5a. usually symmetrically. proximal joints of the hands and feet. accumulates in joint cavity. whose lining cells become hypertrophic and hyperplastic. hyperemia. called rheumatoid factosr (RF). and infiltration by small and large lymphocytes. collagen and immunoglobulin are present in joint cavities of seropositive patients. elbows. the wrists. but then may involve.  As the pannus ages. some authors have suggested Epstein-Barr virus (EBV) infection. ankles. 2 to 3 mm “rice” bodies. or they may be telescoped into each other. indicating the presence of both humoral and cellular immune response arises. RF forms locally in joint fluid. cell-mediated immune systems also contribute to the pathogenesis of the articular and extra-articular manifestations of RA. and displacement or increasing approximation of the ends of the bones. These factors are against the own immunoglobulins (often IgG) and are of considerable complexity. progressive narrowing of the joint space.  An exudate containing polymorphonuclear leukocytes. Morphology of RA Main morphological appearance of RA is synovitis RA generally first affects the small. Third stage  Fibrous and bony ankylosis can result. they are capable of acting as antiglobulins and of forming complexes with abnormal antigenic gammaglobulins in vivo and in vitro. fibronectin. plasmoblasts. vascularity decreases. plasma cells. synoviocytic hyperplasia. and an intense lymphoplasmacytic and hystiocytic infiltrate take place. The resultant accumulation of neutrophils contributes to the pathogenesis of the joint disease.  Other features include rheumatoid nodules (or rheumatoid granuloma) in subcutaneous tissues (areas of necrosis surrounded by palisade of fibroblasts and white cells at pressure . and in addition to circulating immune complexes.97  Females are affected three times more often than males and there is peak prevalence in the third to fourth decades of life. The last-mentioned produce IL-1 and tumor necrosis factor. leading to changes very reminiscent of degenerative joint disease. the fibrosis and collagenization lead to shrinkage of the capsule.  Closely opposing bones may become fused by bone bridges developing in the scar tissue. The cells and mediators that likely play a role in the RA include neutrophils. The trigger for these immunologic reactions remains unknown. and knees. may with ingested immune complexes.  There often are small areas of superficial necrosis of synovial lining cells with formation of superficial erosions covered by fibrinoid deposits. and macrophages. cytokines known to stimulate release of collagenases and other lytic enzymes. Second stage  Hypertrophy of the synovium. lymphocytes.

Some of the total morbidity of RA is caused by GI bleeding from long-term aspirin therapy. Amyloidosis is a late complication of RA with data on the frequency varying from 25% to 60%. each factor may be necessary but not enough for clinical expression of . as. remitting and relasping. Lymph nodes show hyperplasia and. The result is focal fibrosis. Clinical features       Variable. hormonal.  The cause of SLE remains unknown. The lucky patient experiences mild transient disease without sequelae. and serosal membranes. and tend to develop in patients with high RF titers. fibrinous inflammatory lesions of lungs. characterized by a bewildering array of autoantibodies. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) SLE (Libmnan-Sacks disease) is the classic prototype of the multisystem disease of autoimmune origin. Pulmonary lesions may be focal and granulematous or diffuse. with rapidly progressive development of joint deformities. a granuloma of a few millimeters to several centimeters in size.  Antinuclear antibodies are directed against several nuclear antigens and can be grouped into four categories: (1) antibodies to DNA. and musculoskeletal pain before joint involvement occurs.  SLE appears to be a complex disorder of multifactorial origin resulting from interactions among genetic. Extra-articular manifestations (mentioned above). (3) antibodies to nonhistone proteins bound to RNA. Most patients experience a prodrome of malaise. with focal accumulation of lymphocytes and plasma cells. Some authors consider that RNA virus may cause it. and nonspecific. fever. and eyes. Occlusion of the large vessels can cause gangrene of the terminal phalanges of fingers or toes. although infrequent. granulomas. are rarely the presenting features of the disease. Characteristic deformities are radial deviation of the wrist with ulnar deviation of the fingers. In this complex web. it is chronic. and endocardium. In a minority the onset in acute. SLE is predominantly a disease of women.  Likely most autoimmune diseases. fatigue. these antibodies are of major pathogenetic significance. but most has fluctuating disease with the greatest progression during the initial 4 to 5 years. peripheral nerves. interstitial. The most common extra-articular lesion       The most common extra-articular lesion is the subcutaneous nodule. kidney. Vasculitis associated with deposition of immune complexes in vessel walls is seen especially in patients with high serum titers of IgM-RF complex.98 points such as elbows). Apart from their value in the diagnosis and management of patients with SLE. developing usually in areas close to the joints and subject to minor mechanical insults. acute vasculitis (in patients with high rheumatoid factors). myocardium. infections from steroid use. with frequency of 1 in 700 among women between ages of 20 and 64 and female to-male ratio of 9:1. and environmental factors acting in concert to cause activation of helper T cells and B cells that results in the secretion of several species of autoantibodies. particularly antinuclear antibodies. for example. and (4) antibodies to nuclear antigens. occlusion of the vessel may result in ischemia and microinfarcts. often febrile illness characterized principally by injury to the skin. myocardium. Acute or insidious in its onset. but the existence of a seemingly limitless number of antibodies in these patients against self-constituents indicates that the fundamental defect in SLE is a failure of the regulatory mechanisms that sustain self-tolerance. fibrosis. in the immune complex-mediated glomerulonephritis so typical of this disease. or amyloidosis in long-term severe disease. pericardium. Several types of scleritis and retinopathy have been described in about 1% of patients with rheumatoid disease. The death is caused by uremia.  Antibodies have been identified against an array of nuclear and cytoplasmic components of the cell that are either organ or species specific. and amyloidosis. (2) antibodies to histones. pleura. vasculitis. joints. or intraalveolar. Cardiac lesions may involve the pericardium. less commonly. granulomas.

Except for the blood. 3. 5. but a similar rash may also be seen on the extremities and trunk. almost all cases of SLE show some renal abnormality. It should be noted. 2. Normal by light. maculopapular lesions. Histologically.  An acute necrotizing vasculitis involving small arteries and arterioles may be present in any tissue although skin and muscles are most commonly affected. Changes of sclerotic character caused by the above changes. lymph nodes and the vascular walls. the typical lesion being a nonserosive synovitis with little deformity. there is variable edema and perivascular mononuclear infiltrates. the involved areas show liquefactive degeneration of the basal layer of the epidermis together with edema at the dermal junction. This group is characterized by onion-like sclerosis in the spleen. This phenomen characterizes LSE. The shape of the nuclei does not change but they gradually lose DNA and look pale after stain. 5. electron. The latter fact distinguishes this arthritis from that seen in rheumatoid . but if immunofluorescence and electron microscopy are included in the examination of biopsy material. Urticaria. Visceral manifestations of LSE The most characteristic lesions result from the deposition of immune complexes and are found in the blood vessels. and ulcerations also occur. Membranous glomerulonephritis (class 5).99 the disease. On light microscopic examination. The constellation of clinical. and skin. hematoxylin bodies. Diffuse prolirefative glomerulonephritis (class 4). The skin is involved in the majority of patients. reflecting the variability of the clinical manifestations and the course of the disease in individual patients. bullae. Neutrophils and macrophages phagocytize hematoxylin bodies and form so-called “lupus cells”. which is quite fare. Mesangial lupus glomerulonephritis (class 2). they can be found in the bone marrow. that none of these patterns are specific for lupus. According to WHO morphologic classification of lupus nephritis. Nuclear pathology in the cells of all organs and tissues. Macrophagic activity is increased. producing so-called “onion-skin” lesions. Acute necrotic and degenerative changes of the connective tissue (all stages of disorganization). Subacute interstitial inflammation of all organs including nervous system with involvement of microcirculation (capillaritis. the nucleus disintegrates into granules. Focal proliferative glomerulonephritis (class 3).e. serologic. Their presence in the blood is a significant sign of SLE. SLE is characterized by different cellular and tissue changes which can be divided into 5 groups: 1. 4. connective tissue. arteriolitis. i. these vascular lesions involve the central arteries and are characterized by marked perivascular fibrosis. 2. Joint involvement is frequent. Vasculitis with fibrinoid necrosis of the vessels may be prominent. the kidney appears to be involved in 60 to 70% of cases. In the spleen.  Joints.  Kidney. 4. however. vessels undergo fibrous thickening with narrowing lumen. and immunofluorescent microscopy (class 1). kidneys. Fibrinoid deposits characterize the vessel walls of arteries. It can also be said that none of these morphologic changes is pathognomic. spleen. In chronic stages. 3. Changes of the immune system. Focal accumulations of leukocytes with marked plasmatization are present in the central and peripheral organs. Characteristic erythema in the bridge of the nose and cheeks (facial “butterfly”) occurs. particularly in the lymph nodes. the relative importance of various factors may vary from individual to individual.  Skin. and morphologic changes is essential for diagnosis. Exposure to sunlight incites or accentuates the erythema. vasculitis). Morphology The morphologic changes in SLE are extremely variable. After the death of the cell. five patterns are recognized: 1. In the dermis.

heart. calcinosis. subacute. heart. Morphology. lungs. which results in complete immobility of the spinal column. inflammatory and sclerotic changes are observed in the heart. but it is clinically insignificant. It may occur at any age. and breast. Etiology: infectious-allergic factor. the disease is called polymyositis.  Cardiovascular system. Degenerative. The skin becomes dense. The disease mainly occurs in men with antigen histocompatibility HLA-B27. Inflammation of the serosal lining membranes may be acute. Secondary form is frequently observed in cancer of ovaries. The nonbacterial verrucous endocarditis takes the form of single or multiple irregular 1-to3mm warty deposits on any valve in the heart. and alimentary tract. The most common causes of death are renal failure (uremia) and intercurrent infections.100 disease. The complications and the causes of death depend on the visceral lesions (kidneys. Hyperplasia against the background of plasmatization is observed in the immune organs. distinctively on either surface of the leaflets. cellular reactions are observed. fibrosing alveolitis and diffuse interstitial fibrosis are found out. genetic factors causing disturbances in collagen synthesis cannot be excluded. All stages of connective tissue disorganization against the background of slight cellular reaction are noted in the skin and internal organs. Morphology. termed “true sclerodennic kidney”. Later they become thickened. In lungs the pneumanitis. Etiology. amyloidosis in kidneys. may also be present but is less common. Involvement of peripheral joints and inner organs is possible. Striated muscles. manifested as nonspecific mononuclear cell infiltration. so-called Libman-Sacks endocarditis was more common. and coated with a shaggy fibrous tissue that may lead to partial or total obliteration of the serosal cavity. growth of stroma in the cavity of the joint and its-bony metaplasia with development of bone ankylosis and limitation of their mobility. Primary form in children is caused by genetic factor. the mesothelial surfaces are sometimes covered with fibrinous exudate. lungs. Morphology. Clinico-morpholbgical forms: 1) Primary (idiopathic). Visceral changes: chronic inflammation and sclerosis of aorta. lungs). BECHTEREW’S DISEASE    Bechterew's disease is a chronic disease involving joints and ligaments of the spine causing its immobility. In the era before the widespread use of steroids. The same process with bone formation develops in intervertebral disks. During the acute phase. Abnormal collagen disintegrates quickly and is followed by sclerosis. Myocarditis. In the acute phases of arthritis in SLE. edema. Development of large-focus cardiosclerosis.  Spleen. Patients treated with steroids and immunosuppressive drugs incur the usual risks associated with such therapy.  Lungs. opaque. and diaphragm. mainly in women. followed by diffuse central nervous system disease. 2) Secondary (tumor). Degeneration. there is exudation of neutrophils and fibrin into the synovium and a perivascular mononuclear cell infiltrate in the synovial tissue. lungs. DERMATOMYOSITIS    Dermatomyositis is a chronic rheumatic disease involving striated and in rare cases smooth muscles and skin. or chronic. It manifests by acute renal failure. Involvement is manifested primarily in the form of pericarditis. Valvular endocarditis may occur. spine injury and hereditary factors.  Serosal cavities. its mobility is poor. fibrosis of the lungs and subpleural cavities (basal pneumosclcrosis) are possible. necrosis. Viruses. If the skin is not damaged. stomach. the muscles of the pharynx. SYSTEMIC SCLERODERMA     Systemic scleroderma is chronic disease with skin involvement and visceral manifestations. The spleen may be moderately enlarged. Destructive inflammatory changes in the tissues of small joints of the spinal column resembling those in rheumatoid arthritis with destruction of articular cartilages. Cortical necrosis may develop when the vessels of the kidneys are involved. larynx. . ocular muscles are involved. The condition results in sclerosis and hyalinosis.

3. Bacterial pneumonia. Injury to mucociliary apparatus (as with cigarette or other smoke / gaseous inhalations). Congestion and Edema predominates in the first 24 hours. which cause these diseases. 4. subacute. drug effects). Etiologic classification of pneumonia: 1. 2. b) Legionella pneumonia. Important factors interfering with normal lung defenses are 1. e) Lipid pneumonia. Most lobar pneumonias are caused by pneumococci and Klebsiella pneumonia which enter the lungs via the airways. 2. which spreads throughout the lobe through pores of Kohn and . 5. There are a lot of diseases. 3. One or occasionally several lobes of the lung are involved. constantly relapsing and chronic. or by direct spread across the diaphragm from the subphrenic source. The initial response to the organism is edema. 2. Lobar pneumonia. Croupous pneumonia is infectious-allergic infection and involves a lobe of lung. diabetics.  Pleural involvement occurs commonly in lobar pneumonia Pneumococcal pneumonia typically presents the picture of lobar pneumonia. and patients with multiple myeloma or circle cell disease. Acute and chronic bronchitis. lobular. Fibrinous exudates in alveoli are presence. Accumulation of secretions. and alveolar mechanisms to filter. Other types of pneumonias: a) Pneumocystis carini pneumonia. pleurapneumonia. Decreased cough reflex leading to aspiration (seen in coma. Edema/congestion (CIHD). and clear inhaled organisms and particles.  Hypersensivity of immediate type plays an important role in pathogenesis. of pulmonary system as well as the etiologic factors. destructive processes (abscess and gangrene). Lobar pneumonia    Synonyms: crupous. The most common route is the airways. d) Hypostatic pneumonia. Viral and mycoplasmal pneumonia. by traumatic implantation. alcoholics. Pneumonias    Pneumonia is acute inflammation of the respiratory tract with deposition of intraalveolar exudates. anesthesia. Pulmonary protective mechanisms include nasal. DISEASES OF RESPIRATORY SYSTEM ACUTE BACTERIAL INFECTIONS OF THE LUNGS     Occur when normal lung or systemic protective mechanisms are impaired. Bronchopneumonia (lobular pneumonia). Clinical-morphological classification: 1. probably through the lymphatics. spleenectomized subjects. chronic non-specific pulmonary diseases and cancer of lungs are the most common. oxygen toxicity). Interstitial pneumonia. neutralize. through the bloodstream. tracheobronchial.  The pneumococcus continues to be responsible for 30% to 80% or more of communityacquired pneumonias.  Groups at particular risk include the very young and very old.101  Each form may be acute. Decreased phagocytic /bactericidal function of the alveolar macrophage (as a result of alcohol. bronchial asthma. 3. fibrinous. Pathogenic organisms gain access to the lung through the airways. tobacco. pneumonia. c) Aspiration pneumonia.  Traditionally the progress of the disease is divided into four stages: 1.

hemophylus influenzae. According to extent may be acynous. lobular. and coliform bacteria. pericarditis and other organs. but organization may occur and result in fibrous scarring in some cases. firm. Morphology     Initially bronchi are affected. bacterial endocarditis. Lung abscess results from the breakdown of alveolar walls. inflammation spreads to parenchyma of lungs with accumulation of exudates in the alveoli. Red hepatization (2 days) describes lung tissue with confluent acute exudate containing neutrophils and red cells. In adults streptococcal pneumonia like other pneumonias usually occurs in elderly. 4. Outcomes and complications: resolution of the exudates usually restores normal lung structure. severely debilitated patients. At this stage an involved lobe appears distended. and empyema. Complications: Carnification is organization of fibrinoid exudate. in patients undergoing long-term dialysis. Gray hepatization (4-6 days) follows. The interstitial infiltrate also extends into the adjacent alveolar walls. hemorrhagic or mixed exudates filling airspaces and airways. streptococci. and fluid exudes from the cut surface. The distinctive microscopic feature of streptococcal pneumonia is greater interstitial involvement than in other bacterial pneumonias. staphylococci. Staphylococcal pneumonia   Staphylococcal pneumonia usually occurs either in the presence of a source of bacteremia or after viral infection. There is necrosis of the epithelium of distal airways with infiltration of the bronchial walls by neutrophils and mononuclear cells. Depending pathogenesis autoinfectional bronchopneumonia may be aspirationous. moist. 3. segmental. Bronchopneumonia often arises due to autoinfection. hypostatic. immunodificiency. the lungs show dispersed.102 2. Hematogenous pneumonia is seen in those with soft-tissue infections. Lobe is liver-like. Diabetes is also a risk factor. Resolution (9-11 days) is the favorable final stage in which consolidated exudates undergoes enzymatic and cellular degradation and clearance. arthritis. Gangrene. postoperative.  1. 5. elevated. focal areas of palpable consolidation and suppuration. The pleura are shiny. Bronchopneumonia often is a complication of others disease. Abscess formation. usually about bronchi and bronchioles. Empyema (spread of infection to pleural cavity). serous. as the red cells disintegrate and the remaining fibrinous-suppurative exudates persist. The most often agents are bacterias: pneumococci. Then. Streptococcal pneumonia     Beta-hemolytic streptococci are an uncommon cause of pneumonia at the present time.  bronchioles. Bronchopneumonia (focal pneumonia)      Bronchopneumonia is marked by patchy exudative consolidation of lung parenchyma Polyetiologic. 2. Aggressive disease may produce abscess. pleurisy. Normal structure is restored. 3. Infections caused by this microbe in the newborn are discussed elsewhere. Grossly. giving a gray-brown gross appearance. and miliary. and deep red of purple. Causes of death are acute cardiac-respiratory insufficiency and purulent complications. Histological features consist of acute (neutrophilic) suppurative. The lower lobe is usually the site of major involvement. 4. Bacteremic spread leads to purulent meningitis. giving a red. The airways appear thickened and are filled with a hemorrhagic or purulent exudate. The lesions may appear as septic infarcts that are yellow and . pseudomonas aeruginosa. The pneumonia is lobular with consolidated patches clearly centered on terminal bronchioles.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE The term Chronic Obstructive Pulmonary disease (COPD) refers to a group of conditions that share a major symptom – dyspnea . Chronic Bronchitis The widely accepted definition of chronic bronchitis is a clinical one – chronic bronchitis (CB) is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years. or they may be rounded patches of necrotizing pneumonia that break down. reflecting diffuse alveolar damage. . so common among habitual smokers and inhabitants of smog-laden cities. A predominance of interstitial pneumonitis with widened. amniotic fluid or meconium in infants. The formation of hyaline membranes. Alveoli filled by foamy fluid and pneumocysts. infected material from oral cavity. Pneumocystic pneumonia is characterized by desquamation of alveolar epithelium. It may pattern in AIDS. 2) Right-sided failure. The lesions are those of bronchopneumonia accompanied by a hemorrhagic and necrotizing bronchitis. etc. asthma. ranging from relatively mild upper respiratory tract involvements to severe lower respiratory tract disease.  Obstructive diseases are characterized by increased resistance to airflow because of chronic or recurring expiratory obstruction. these individual disorders – chronic bronchitis. edematous alveolar walls containing a mononuclear inflammatory cell infiltrates. giving rise to abscesses. These substances include food.  In their prototypical forms.103    purulent but preserve to some degree the wedge-shaped configuration of infarcts and are associated with thrombosed vessels. Staphylococcal bronchopneumonia is not rare in children less than 6 months of age. result in varied clinical and pathologic patterns.  Death of the most patients with COPD is due to 1) Respiratory acidosis and coma.  Hypertension of pulmonary circulation and “cor pulmonale” develops in all Chronic Obstructive Pulmonary diseases. Local complications of staphylococcal pneumonia include empyema and bronchopleural fistula. mycoplasma pneumonia.and are accompanied by chronic or recurrent obstruction to air flow within the lung. Staphylococcal pneumonia also results from spread of organisms from the colonized nasopharynx. Interstitial pneumonia Infections by viruses. emphysema – have distinct anatomic and clinical characteristic. is not nearly so trivial as was once thought. gastric contents. etc. Purulent exudate fills the bronchioles and spreads into the adjacent acini. Morphology     Patchy or lobar areas of congestion without the consolidation of bacterial pneumonias. and also hyperemia and inflammatory infiltration of the alveolar septs. 3) Massive collapse of the lung secondary to pneumothorax.  Amyloidosis of kidneys and chronic renal insufficiency may develop often. A notable feature of staphylococcal pneumonia in small children is development of abscesss. pneumocystis carinii. Aspiration pneumonia Aspiration pneumonia results from inhaling different agents into the lungs. Hypostatic pneumonia Hypostatic pneumonia is the term used for the collection of edema fluid and secretions in the dependent parts of the lungs in bed-patients.  This disorder. bronchiectasis.

As CB persists. it is now thought that accompanying alterations in the small airways of the lung can result in physiologically important and early manifestations of the chronic airway obstruction. Cause atypical metaplasia and dysplasia of the respiratory epithelium. 4. due to tumor. Inflammatory infiltration. in which the BE are localized to the obstructed lung segment. Although mucus hypersecretion in large airways is the cause of sputum overproduction. When tumors or aspiration of foreign bodies leads to BE. 2. providing a possible soil for cancerous transformation. Morphology      BE usually affects the lower lobes bilaterally. Congenital or hereditary conditions. Long. Morphology     The hallmark and earliest failure of CB is hypersecretion of mucus in the large airways. The walls of bronchi are thickened and the lumen arc filled with mucus. there is also a marked increase in goblet cells of small airways – small bronchi and bronchioles – leading to excessive mucus production that contributes to airway obstruction. . Goblet cell metaplasia with mucus plugging of the lumen. and is most severe in the more distal bronchi and bronchioles. 3. 2. These dilations may produce: 1. There may be squamous metaplasia of the remaining epithelium. most often caused by tubercle bacillus or staphylococci or mixed infections. It is not responsible for the initiation of CB but is probably significant in maintaining it and may be criterial in producing acute exacerbations. Two sets of factors are important in the genesis of chronic bronchitis: 1. including congenital BE. In the full-down active case. foreign bodies. 3. sometime up to four times normal size. cystic fibrosis. May cause fusiform or even sharply saccular distention (saccular BE) in 6-10 types of bronchus. Pathogenesis. and immune cilia and Kartagener‟s syndromes. Microbiologic infections. Amyloidosis of kidneys. Necrotizing pneumonia. measles. intralobar sequestration of the lung states.104   The role of infection appears to be secondary. particularly those air passages that is most vertical. 2. The pleura is usually fibrotic and thickened with adhesions to the chest wall. and is associated with hypertrophy of the submucosal glands in the trachea and bronchi. BE has many origins and usually develops in association with following conditions: 1. Cut surface has honey-combed appearance. the involvement may be sharply localized to a single segment of the lungs. and occasionally mucous impaction. Outcomes and complications     Lead to “cor pulmonale” and heart failure. most commonly atopic asthma and chronic bronchitis. Fibrosis of bronchiolar wall. or due to diffuse obstructive airway disease. Lead to bronchiectasis. Bronchial obstruction. tube-like enlargements (cylindroid BE) in 1 to 4 type of bronchus. The histologic findings vary with the activity and chronicity of the disease: 1. Clustering of pigmented alveolar macrophages. associated with desquamation of the lining epithelium and extensive areas of necrotizing ulceration. The airways are dilated. 2. Bronchiectasis (BE) BE is chronic necrotizing infection of the bronchi and bronchioles leading to or associated with abnormal dilation of these airways. Histological features of the small airways: 1. Chronic irritation by inhaled substances. there in an intense acute and chronic inflammatory exudation within the walls of bronchi and bronchioles.

along the lobular connective tissue septa. The walls of the emphysematous spaces often contain large amount of black pigment. and increased elastase and decreased alpha-1-AT activity causes to the centriacinar emphysema seen in smokers. accompanied by destruction of their walls. and cigarette smoke activates the alternative compliment pathway. the necrosis completely destroys the bronchial or bronchiolar walls and forms a lung abscess. Outcomes and complications 1. “Cor pulmonale” and chronic cardiac-pulmonary insufficiency. Pulmonary hemorrhage. Amyloidosis are less frequent complications of BE. the central or proximal parts of the acini. Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis. Panacinar (panlobular) emphysema. indeed. The increased recruitment of neutrophils into the lung is likely to result. the distention of airspaces in the opposite lung following unilateral pneumonectomy. In addition. Classification Although the term “emphysema” is sometimes loosely applied to diverse conditions. 3. there are four types: 1. the most plausible hypothesis to account for the destruction of alveolar walls is the protease-antiprotease mechanism. In some instances. but the distal part is dominantly involved. 3. and at the margins of the lobules. 5. In this type the proximal portion of the acinus is normal. emphysema is seen to result from the destructive effect of the high protease activity in subjects with low antiprotease activity. In contrast. Empyema of the pleura. 2. with the resultant influx of neutrophils and macrophages. 2. 7. macrophage elastase is not inhibited by alpha-1 –AT and. In addition. are affected. Pathogenesis While details of the genesis of the two common forms of emphysema – centiacinar and panacinar – remain unsettled. often in association with chronic bronchitis. Smoking enhances elastolytic proteases activity in macrophages. this release being stimulated by smoking. whereas distal alveoli are spared. In this type the acini are uniformly enlarged from the level at the respiratory bronchiole to the terminal blind alveoli. . 3. Oxidants in cigarette smoke and oxygen free radicals secreted by neutrophils inhibit alpha-1AT and thus decrease net antielastase activity in smokers. Pulmonary abscess. 3. and without obvious fibrosis. the enlargement of airspaces unaccompanied by destruction is termed overinflation. Smoking stimulates release of elastase from neutrophils. formed by respiratory bronchioles. 2. Inflammation around bronchi and bronchioles and in the septa is common. It is thus postulated that impaction of smoke particles in the small bronchi and bronchioles. can proteolytically digest this enzyme. Centriacinar (cenrolobular) emphysema. Metastatic brain abscess. 4. nicotine is chemotactic for neutrophils. 6. Smokers have greater numbers of neutrophils and macrophages in their alveoli. 4. some lesions of so-called coal workers‟ pneumoconiosis bear a striking resemblance to centriacinar emphysema. The protease-antiprotease hypothesis also explains the deleterious effect of cigarette smoking. Moderate-to-severe degrees of emphysema occur predominantly in heavy smokers. The distinctive feature of this type is the pattern of involvement of the lobules. Emphysema Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspace distal to the terminal bronchiole.105 2. Fibrosis of the bronchial and bronchiolar walls and peribronchial fibrosis develop in the more chronic cases. Paraseptal (distal acinar) emphysema. This type of emphysema probably underlies many of the cases of spontaneous pneumothorax in young adults. Thus. from the release by activated alveolar macrophages of neutrophil chemotactic factors. 1. for example. This type of emphysema is associated with alpha-1-antitrypsin deficiency. The emphysema is more striking adjacent to the pleura. in part.

produces voluminous lungs. pulmonary infections. Pathogenesis   Chronic airway inflammation involving many cell types and inflammatory mediators accompanies the bronchial hyper-responsiveness of asthma. and the distribution of damage within the pulmonary lobule. The entrance of air into the connective tissue stroma of the lung. the relationship of the inflammatory cells and their mediators to airway hyper-reactivity is not fully understood. intrinsic BA is initiated by diverse. 2. Panacinar emphysema. Nevertheless. Interstitial E. it may be the most common form of emphysema. Generally. or subcutaneous tissue is designated interstitial emphysema. refers merely to at any form of E. is almost invariably associated with scarring. In most instances. and allergic bronchopulmonary aspergillosis (bronchial colonization with aspergillus organisms followed by development of IgE antibodies). Large apical blebs or bulla are more characteristic of irregular emphysema secondary to scarring. as careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process. The macroscopic signs of centriacinar emphysema are less impressive. A severe and unremitting type of the disease termed status asthmaticus may prove fatal. producing even larger abnormal airspaces and possibly blebs or bulla. these foci of irregular emphysema are asymptomatic. so named because the acinus is the irregularly involved. the complete destruction of septal walls. Types of emphysema according to cause 1. The lungs may not appear particularly pale or voluminous unless the disease is well advanced. Microscopical examination is accessory to visualize the abnormal fenestrations in the walls of the alveoli. mediastinum.106 4. stress. refers to the overdistended. BA. Subtypes include atopic (allergic). 2. there may or may not be evidence of bronchitis or bronchiolitis. especially those caused by viruses. This term is sometimes used to designate dilation of alveoli but not destruction of septal walls in response to loss of lung substance elsewhere. Thus. Classification 1. inhaled irrigants (pollutants such as sulfur dioxide). occupational BA (many forms). owing to increased responsiveness of the tracheobronchial tree to various stimuli. including aspirin. leading to episodic. when well developed. sometimes voluminous lungs found in the aged. as mentioned. Extrinsic BA is initiated by a type 1 hypersensitivity reaction induced by exposure to an extrinsic antigen. Often the respiratory bronchioles and vasculature of the lung are deformed and compressed by the emphysematous distortion of the airspaces. Irregular emphysema. the upper two-thirds of the lungs are more severely affected. that produces large subpleural blebs or bullae (spaces more than 1 cm in diameter in the distended state). adjacent alveoli fuse. reversible bronchoconstriction. and. Bronchial Asthma (BA) Bronchial asthma is a disease characterized by hyper-reactive airways. Senile E. Morphology       The diagnosis and classification of the emphysemas are based on naked eye (or hand lens) examination of lungs fixed in a state of inflation. It is best exemplified by the hyperexpansion of the residual lung parenchyma that follows surgical removal of a diseased lung or lobe. Compensatory E. Morphology . and exercise. 4. cold. often overlapping the heart and hiding it when the anterior chest wall is removed. With advance of the disease. nonimmune mechanisms. In contrast. Bullous E. Obstructive overinflation refers to the condition in which the lung expands because air is trapped within it. 3.

. but it appears that the pathology in nonfatal cases is similar. there are still cases in which no reasonable basis for the LA formation can be identified. These are referred to as “primary cryptogenic” LA.  Continued infection leads to large. which give. hemorrhage.Septic embolism.  When all these causes are excluded.Thickening of the basement membrane of the bronchial epithelium. the severe acute paroxysm persists for days and even weeks. ventilatory function may be so impaired as to cause severe cyanosis and even death. and bronchiectases play important roles in their development.  The cardinal histologic change in all abscesses is suppurative destruction of the lung parenchyma within the central area of cavitation. depending on the presence or absence of a communication with one of the air passages. these symptoms persist at a low level all the time.An increase in size of the submucosal glands. .107 The morphologic changes in asthma have been described principally in patients dying of status asthmaticus. designated gangrene of the lung. Chronic Lung Abscess (LA) The term “LA” describes a local suppurative process within the lung characterized by necrosis of lung tissue. and there may be small areas of atelectasis. a reflection of prolonged bronchoconstriction. rise to the wellknown Curschmann‟s spirals. multilocular cavities with poor demarcation of their margins.Emphysematous changes sometimes occur. Idiopathic Pulmonary Fibrosis .  The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick.  The causative organisms are introduced by the following mechanisms: . Morphology    Abscesses vary in diameter from lesions of a few millimeters to large cavities of 5 to 6 cm. the raising of copious mucous secretions provides considerable relief of the respiratory difficulty.Obstructive tumors. . the lungs are overdistended because of overinflation. They may affect any part of the lung and may be single or multiple. the contained exudate may be partially drained to create an air-containing cavity. Complications include extension of the infection into the pleural cavity. under these circumstances. fetid.Hypertrophy of the bronchial wall muscle. . bronchitis may occur. The classic asthmatic attack lasts up to several hours and is followed by prolonged coughing. the development of brain abscesses or meningitis from septic emboli.  A reactive fibrous wall often surrounds chronic abscesses. . which form 5 to50% of the cellular infiltrate.  Numerous eosinophils and Charcot-Leyden crystals are present. . with a prominence of eosinophils. .Edema and inflammatory infiltrate in the bronchial walls. status asthmaticus. the mucous plaques whorls of shed epithelium.Miscellaneous. dental sepsis.Direct traumatic punctures. .Aspiration of infective material.  The other characteristic histologic findings of BA include: . .  Histologically.  When such communications exist. bronchial infections. tenacious mucous plaques. and if chronic bacterial infection has supervened. and rarely reactive secondary amyloidosis.  Superimposed saprophytic infections are prone to flourishing within the already necrotic debris of the abscess cavity. and. The cavity may or may not be filled with suppurative debris.  Grossly.Antecedent primary bacterial infection. green-black. In its most severe form. In some patients.  Oropharyngeal surgical procedures.

enlarged. Etiophathogenesis       Infectious agents are staphylococcus. DISEASES OF ALIMENTARY SYSTEMS Tonsillitis   Tonsillitis is infectious disease and is characterized by inflammatory changes in the crypts of the adenoids and the tonsils on the anterior wall of the pharynx. Tonsils and adenoids are usually unapparent in early infancy. Classification Acute tonsillitis:        Cattharal tonsillitis is characterized by hyperemia and serous or mucous leucocytic infiltration. Purulent tonsillitis is characterized by phlegmonous inflammation or the formation of abscesses. It is so called “idiopathic pulmonary fibrosis” or “cryptogenic fibrosing alveolitis” or “chronic interstitial pneumonitis” Morphology      Pathological changes are bilateral and widespread. thick-walled air spaces) develops in parts of lung. These tissues are part of the bursal system of immunity and consist mostly of B cells. Lymphoid tissue is distributed on the posterior pharyngeal wall and under the tongue. ulceration of the epithelium are morphological features of chronic tonsillitis. Necrotic tonsillitis the ulceration occurs and can be in leukemia and scarlet fever. Fibrinous tonsillitis the deposition of whitish-yellowish fibrinous films (in diphtheria) occurs. Follicular tonsillitis is characterized by hyperplasia of tonsils. Tonsillitis can be acute and chronic. changes vary according to the stage of the disease with formation of hyaline membranes. . streptococcus. Transephithelial. increasing of crypts.108 Diffuse interstitial fibrosis occurs as a result of different pulmonary diseases. adenovirus and bacterium‟s assotiations. There is edema and cellular infiltrate in the alveolar septa in early stage. There is organization of the alveolar exudate and replacement fibrosis in the alveoli and in the interstitial septal wall with variable amount of inflammation in advanced stage. and sometimes purulent exudates and abscesses. hematogenic pathways are responsible for the transmission. sclerosis of tonsil‟s capsule. Tonsils are enlarged due to edema and leucocytic infiltration. which are located in crypts. Hyperplasia and sclerosis of lymphoid tissue. Microscopically. may develop in the crypts of the adenoids and the tonsils on the anterior wall of the pharynx. but gradually undergo hypertrophy and hyperplasia to rich their relatively greatest mass between 2 and 5 years of age.e. Chronic tonsillitis   Chronic tonsillitis is characterized by the persistence of infection or due to relapse of acute tonsillitis. Honey-combing (i. Cryptous tonsillitis is characterized by the deposition of the serous. Macroscopically the lungs are dense. Tonsils are enlarged and hyperemic. Leucocytic infiltration and necrosis of follicles take place. mucous or purulent exudates. reduced volume. Autoinfection is most often cause of tonsillitis against a background the cooling and trauma Acute edema and erythema. Their location is such that they are exposed to inspired air and food and whatever antigens may be carried in either one. Gangrenous tonsillitis the ulceration and hemorrhages occurs also. but not as masses of nodes with crypts such as composes the palatine adenoids and facial tonsils.

This is known as retropharyngeal abscess. The characteristic findings and fever. If the condition is untreated. Peritonsillar cellulitis and abscess are characterized by an extremely sore throat and often high fever. low-grade fever. failure to gain weight. The retropharyngeal nodes drain both the adenoids and the nasopharynx and can become chronically infected. Consequently. hyperextension of the neck. Necrotic (or Corrosive). are extremely common. The importance of this disease is that it is commonly a precursor of rheumatic fever or one form of glomerulonephritis. Inspection of the tonsils is of limited help during acute episode. toxic and bacterial agents. Complication of tonsillitis      Extension of tonsillar infection can take place in the surrounding tissues and is called peritonsillar abscess or quinsy. Chronic gastritis      Chronic inflammatory changes in the mucosa of the stomach. 3. 6. which are almost sensitive to penicillin. Retropharyngeal abscess is virtually limited to infants in the first 2 years of life. These complications of tonsillitis are usually caused by B-hemolytic streptococci. Phlegmonous gastritis. 5. Morphologic classification of acute gastritis: 1. Our understanding of the etiology and mechanism of gastritis and gastroduodenal ulceration has been radically altered by the discovery of specific infective agent Helicobacter pylori. with various degrees of loss of the specialized glandular tissue. cor pulmonale. drugs. Fibrinous gastritis. There is prominence of the infected pharyngeal wall but swelling is almost always unilateral. the widespread use of antibiotics to treat streptococcal pharingitis has been associated with less suppuration in the peritonsillar of retropharyngeal spaces. dysplasia and atypia of the surface epithelium. Hemorrhagic gastritis. sleep apnea. Glandular atrophy is often accompanied by metaplasia. although often clinically silent. Clasification The histological classification incorporates three main positions: 1. Catarrhal gastritis. The Sidney System is a new classification based on this recent new knowledge. dysphagia. retention. or recurrent sore throats with high fever.109   Chronic infection can present as anorexia. Collectively constitute a morphologic continuum of increasingly intense inflammation of mucosa accompanied by progressively more marked atrophy of the mucosa glands. Etiology. and noisy respirations. Hypertrophy can be considerable and lead to mouth breathing. it may lead to significant swelling and even occlusion of the oral pharynx. and. Persistent anterior and posterior cervical adenopathy in the absence of generalized lymphadenopathy is evidence of chronic or recurrent infection. 4. . Pseudomembranous. rarely. Acute gastritis Acute inflammation develops due to injury of the mucosa by the alimentary. It incorporates two separate divisions: histological and endoscopic. or even upper airway obstruction. 2. Gastritis Gastritis is an inflammation of gastric mucosa and can be acute and chronic.

110
2. Topography (i.e.-site affected: antrum, body or both).
3. Morphology (including information about activity, intestinal metaplasia - graded as
mild, moderate or severe).
The three main types of chronic gastritis are examples of this classification according to
topography use:
I. Autoimmune associated chronic pangaslritis with severe atrophy (Type A fundal gastritis)
 Associated with circulating antibodies to parietal cells and intrinsic factor and complete loss
of parietal cells.
 Loss of parietal cells leads to hypo- or achlorhydria, hypergastrinemia, inadequate synthesis
of intrinsic factor and vitamin B12 absorption.
 Overt pernicious anemia develops in 10%.
 Associated with Hashimoto‟s thyroiditis and Addison‟s disease, hence the term
autoimmune gastritis.
 Intestinal metaplasia and dysplasia may occur and possibly resulting in gastric carcinoma.
II. Helicobacter pylori associated chronic gastritis of the antrum with moderate activity (Type B
gastritis)
 The most common form of gastritis in all age groups.
 Background factors are environmental such as intoxication, abnormal dietary, and alcohol.
 Associated with gastric atrophy, intestinal metaplasia, gastric polyps, and gastric cancer.
 Initially superficial, gradually becomes deeper to affect the entire mucosa with glandular
atrophy, leading to “chronic atrophic gastritis”.
 Colonization of mucous layer and surface of mucosal cells with curved organisms, with little
to no tissue invasion, confined to areas of gastric mucosa.
 Small foci of neutrophils, some passing to surface or into superficial crypt lumen occur,
superimposed on a variable background of chronic gastritis (active chronic gastritis with
abundant neutrophils).
III. Reflux-gastritis (formerly known as Type C gastritis)
 Associated with reflux of duodenal contents in stomach.
 May occur after gastric surgery, or with weakened pyloric sphincter tone.
 Localization is antrum.
 Achlorhydria and hypergastrinemia is absent.
According to topography
1. Antral gastritis.
2. Fundal gastritis.
3. Pangastritis.
According to morphology
 Chronic superficial gastritis (early stage): lymphocytes and plasma cells in the upper third
of the lamina propria, some mucosal flattening.
 Chronic atrophic gastritis (later stage): flattening of rugal folds, mucosa thinned and
flattened, chronic inflammation of full thickness of the mucosa, loss of glands, metaplasia of
mucosa to the intestinal type.

Peptic Ulcer Disease
Ulcerative disease is chronic disease with development chronic recurrent peptic ulcer.
Background factors:
 Age. Often diagnosed in middle-aged to elder adults, but may appear in young adult life.
 Common in industrialized nations.
 Sex. Mail-female ratio 3:1.
 Familial tendency and genetic factors for duodenal ulcer.
 Environmental and geographical factors.
 Dietary habits.
 The ingestion of drugs (especially aspirin, corticosteroids).
 Stresses may be important.
 Cigarette smoking and alcohol.
Pathogenesis
Hypersecretion of gastric juice and emotional factors have been considered to be important in
the pathogenesis of peptic ulcers. The gastroduodenal mucous membrane is protected against
digestion of normal gastric secretions not only by its mucus coating but also by dilution and

111
neutralization with swallowed food, saliva, and regurgitated duodenal fluids. This is considered to be
the result of vagal stimulation and can be abolished by section of the vagus nerve. The spiral
bacterium Helicobacter (campylobacter pylori) has been frequently isolated from patients with
gastritis or peptic ulcer disease, but its pathogenic role remains to be determined. Prostaglandin
deficiency has also been implicated as a possible cause of peptic ulcer disease.
For duodenal ulcers, the most important cause is excess exposure to acid and pepsin. Major
influences for duodenal ulcers:
 Hypertone of vagus with increasing of acid-peptic factors.
 Abnormally rapid gastric emptying, exposing the duodenum to a greater acid load.
 Increasing of the level of ACTG and glucocorticoids.
 Duodenal ulcer has been associated with tension, stress, and anxiety but this is by no means
always the case and there is no agreement on the importance of stress in its pathogenesis.
For gastric ulcers, breakdown in mucosal defenses appears to be most important. Major
influences for gastric ulcers:
 Suppression of hypothalamic and hypophysic functions.
 Hypotone of vagus and decreasing of gastric secretion.
 May involve decreased pyloric sphincter tone, and reflux of bile acids.
 Weakening of protective factors of gastric mucosa.
 Exogenous agents that damage the mucosa are more likely to cause gastric ulcers than
duodenal ulcers (alcohol, drugs, chemical substance).
 Possible defect in gastric mucus with the presence of Helicobacter.
Morphogenesis and morphology
I. Erosion is superficial necrosis of mucosal epithelial elements.
 These are tiny ulcers, a few millimeters in diameter, which are formed by the digestion of
the mucosal membrane overlying small hemorrhage.
 They are usually multiple and affect all parts of the stomach.
 They occur mostly on the apex of mucosal folds and involve only the mucosa.
 Note that the changes are superficial so that restoration to normal can very quickly occur.
II. Acute ulcer
 Loss of tissue penetrating into the submucosa.
 Location: single or multiple lesions throughout the stomach and duodenum.
 Circular and small, less than 1 cm in diameter.
 Inflammatory reaction absent initially, develops secondarily.
 Massive hemorrhage may be fatal.
 Perforation can lead to peritonitis.
 This type of ulcer usually heals without a visible scar.
III. Chronic peptic ulcer
 The term “chronic” is applied when the pathological changes have penetrated and destroyed
the muscle coat; they are also, of course, of much longer duration than acute ulcers.
 Gastric ulcers are located along the distal lesser curvature, usually within about 5 cm of the
pylorus.
 Duodenal ulcers usually occur in the first centimeter or two distal to the pylorus on the
anterior or posterior wall rather that laterally (kissing ulcers).
 Classic peptic ulcer is small (about 1 cm in the duodenum; 1 to 2,5 cm in the stomach),
round-to-oval. It is characteristically “punched out”, with sharply defined margins, and has
overhanging mucosa producing a flashlike appearance. Its edges are not raised, and the
mucosal folds covering on the ulcer are distinct to its edge. Frequently it has a terraced
structure.
 Malignant gastric ulcers are generally bowel shaped, with margins that are usually sloped
and generally without overhanging mucosa. The edges are raised and indurated, and
nodular mucosal or submucosal thickening interrupts the mucosal folds toward the crater.
 Microscopically:
1. The bed of the ulcer is covered by fibrinous exudate containing fragmented leukocytes.
2. Fibrinoid necrosis.
3. Granulation tissue with plasma cell and lymphocytic infiltration.
4. Fibrous tissue.
The principal complications of peptic ulcer

112
I. Ulcerative-destructive:
 Perforation. Anterior duodenal ulcers may perforate into the free peritoneal cavity, with
resultant peritonitis. The peritonitis from perforated peptic ulcer is initially a chemical
inflammation, but bacterial contamination soon follows. After successful surgical treatment
of the perforation, there is a risk that infected material lodged between the liver and
diaphragm may become sealed off by fibrinous exudate and cause an abscess that may later
infect the pleura.
 Penetration. Extension of the inflammation to the serous coat may result in adhesion to
the adjacent organs. Perforating posterior ulcers more often penetrate the pancreas,
producing intractable pain. Posterior perforation also may occur into the lesser peritoneal
sac, leading to localized peritonitis. The omentum or adhesions to adjacent organs may also
serve to localize peritoneal inflammation.
 Hemorrhage. Both gastric and duodenal ulcers are subject to massive hemorrhage.
Duodenal ulcers are especially prone to perforation. Any ulcer, but especially those located
posterior, may bleed in smaller amounts, producing melena or evidence of occult blood in
the stool. It may be abundant and give rise to “coffee-grounds” vomit. Sometimes a major
artery may be eroded and a large, even fatal, hemorrhage takes place.
II. Ulcerative- cicatricial (obstruction or healing and scarring).
 Pyloric obstruction may be a complication of an ulcer, gastric or duodenal, situated near the
pylorus. It usually results from a combination of cicatricial narrowing and spasm.
 Scarring in the duodenum may lead to serious stricture (pyloric stenosis). The stomach
becomes greatly dilated and hypertrophied and lead to chronic vomiting with alkalosis and
malnutration.
III. Malignization.
The development of carcinoma has been reffered to as one of the complications of peptic ulcer.
It seems probable that carcinoma can develop in a preexisting ulcer, but it is equally probable that it is
a rare event. It is extremely difficult to establish the occurrence of such a sequence of events in any
particular case.
IV. Inflammatory (gastritis, perigastritis, duodenitis, periduodenitis).
V. Mixed.

Appendicitis
Appendicitis results in severe acute or chronic inflammation of the vermiform appendix.
Acute appendicitis

 Acute appendicitis is the most common acute abdominal condition requiring surgery.
 Acute appendicitis is uncommon at the extremes of age and it is most frequently seen in



elder children and young adults.

The most important factor in its pathogenesis is obstruction of the lumen, with the most
frequent cause being a fecalith, a molded mass of inspissated fecal material that may
develop rock-hard consistency.
Other causes of obstruction are scars representing a residuum of previous attacks of
appendicitis, tumors, external bands, and adhesions, rarely masses of parasites, foreign
bodies, and possibly spasm of the muscle at the base of the appendix.
The immediate cause of acute appendicitis is bacterial infection from the intestinal lumen,
though bacterial invasion from the bloodstream in systemic disease is possible.
The appendix may be involved in diseases primarily affecting other portions of the
gastrointestinal tract, such as Crohn‟s disease, typhoid fever, and amebiasis, and in certain
systemic diseases (such as measles).

Clinical-morphological classification of acute appendicitis
1. Simple appendicitis is characterized by hyperemia; small hemorrhages and primary affect
including small foci leucocytes.
2. Superficial appendicitis is characterized by focus of suppurative inflammation in mucosa
and edema. Serous membrane is dim.
3. Destructive forms:
 Flegmonous appendicitis occurs the diffuse infiltration of leucocytes in wall of
appendix. Gross appearance: appendix is increased, swollen; tense and markedly congested
and covered by fibrinous exudate.

113



Flegmonous-ulcerative appendicitis is characterized by flegmonous inflammation
with necrosis and ulceration in mucosa.
Apostematous appendicitis the formation of small abscesses occurs. The primary
inflammatory lesion may increase in intensity and lead to a small abscess in the wall, and
this may perforate.
Gangrenous appendicitis occurs large areas of necrosis, the immediate antecedent of
rupture and may has two causes:
a) Thrombosis and thromboembolism of mesentery artery (primary gangrene of
appendix) due to obstraction of the lumen by fecoliths.
b) Thrombosis due to development of periappendicitis (secondary gangrenous
appendicitis).

The complications of acute appendicitis
1. Necrosis of appendix wall (gangrenous appendicitis), leading to perforation, with subsequent
generalized peritonitis.
2. Involvement of adjacent bowel loops, causing perforation of small bowel.
3. The omentum may become adherent, localizing the peritonitis to the right iliac fossa. Fibrosis
and continued inflammation cause development of a mass in the right iliac fossa. This may
resolve with scarring, may form an abscess that drains to the surface, or may rupture, with
development of generalized peritonitis.
4. Empyema of appendix due to obstruction of proximal parts.
5. Spread of infection by portal vein branches may propagate to the liver; this was formerly an
important cause of portal pyemic abscesses in the liver.
Chronic appendicitis
Chronic appendicitis is characterized by sclerosis and atrophy, lipomatosis and diffuse
infiltration by lymphocytes and hystiocytes.
 Obliteration of part or all of the appendiceal lumen by a mixture of fibrous tissue,
lymphocytes, lymphoid follicles, and nerve bundles is common.
 In the fibrosis causes complete of the lumen, continued mucous secretion might result in
cystic dilatation – mucocele.
 Such a cyst may rupture, giving rise to myxoma peritonei: the mucus-secreting epithelium
is spilled into the peritoneal cavity and loculations of mucin and adhesions result.
Surgically removed appendix may be histologically normal (false-positive clinical diagnosis). If
the appendix is normal, but clinical cymptomes took place is called “false appendicitis”. It may be
due to mimicking acute appendicitis some diseases: salpingitis, ectopic pregnancy, Meckel‟s
diverticulitis, peptic ulcer, and pain cause by trivial pelvic bleeding at the time ovulation.

DISEASES OF THE LIVER



There are various diseases of the liver.
In some instances, the disease is primary to the liver, as in viral hepatitis and hepatocellular
carcinoma.
More often the hepatic involvement is secondary, often to some of the most often diseases
in humans, such as cardiac decompensation, disseminated cancer, alcoholism, and
extrahepatic infections.
Some general aspects of liver disease are reviewed.

Morphologic patterns of hepatic injury
The liver is an inherently simple organ, with a limited repertoire of responses to injurious
events. Regardless of cause, five general reactions may occur.
I. Necrosis. Virtually any significant insult to the liver may cause hepatocyte necrosis.
 In ischemic necrosis, poorly stained mummified hepatocytes remain (coagulative necrosis).
 Necrosis of scattered hepatosytes, clumps, or an entire lobule. Isolated necrotic hepatocytes
appear as eosinophilic rounded - up, shrunken cells and are called Councilman Bodies or
apoptotic bodies).
 Alternatively, hepatocytes may osmotically swell and rupture so-called hydropic
degeneration.

seen in yellow fever. entire lobules (submassive necrosis). and viral particles. hepatocytes may take on a swollen. particularly smoldering forms of viral hepatitis. brucellosis.  Short of outright necrosis. Inflammation. Classification of the liver diseases 1. Inflammation is defined as the influx of acute or chronic inflammatory cells into the liver and is termed hepatitis.  With continuing fibrosis. d) Massive necrosis is most commonly caused by severe chemical and drug toxicity or viral hepatitis. Regeneration is signified by thickening of the hepatocyte cords (the result of hepatocyte proliferation) and some disorganization of the parenchymal structure. tularemia.  Deposition of collagen has lasting consequences on hepatic patterns of blood flow and perfusion of hepatocytes. and herpes or adenovirus infection. V.  Alternatively. copper. Regeneration. retained biliary material may impart a diffuse foamy swollen appearance to the hepatocyte (cholestasis).  In other conditions. 3. the liver is subdivided into nodules of regenerating hepatocytes surrounded by scar tissue. Strictly periportal necrosis is seen primarily in phosphorus poisoning and eclampsia. Degeneration. such as typhoid fever.  The liver has enormous reserve. a) Focal necrosis is most characteristic of microbial infections.  Although inflammation may be secondary to hepatocellular necrosis. The steatosis (fat hepatosis) is the most common chronic one. . b) Centrilobular necrosis is characteristic of ischemic injury and many drug and toxic chemical reaction. Hepatosis (when degeneration and necrosis inflammation in the hepatocytes prevail). Hepatosis may be inherited and acquired.114  Necrosis may be limited to scattered cells within the hepatic lobules (focal necrosis) or involve particular regions of the lobule (zonal necrosis). lymphocytic attack of viable antigen-expressing liver cells is a common cause of liver damage. Hepatosis     The term hepatosis is used to describe degeneration and necrosis in the liver caused by infectious. and regeneration occurs in all but the most fulminant diseases.  Foreign bodies. almost perfect restitution can occur. edematous appearance (ballooning degeneration) with irregularly clumped cytoplasm and large.  In the case of focal hepatocyte necrosis. fibrosis may develop around portal tracts or the central vein or may be deposited directly within the space of Disse. or the whole liver (massive necrosis).  Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. IV. Hepatic tumors.  In the initial stages. II. macroscopic abscesses may occur. such as iron. III. scavenger macrophages quickly generate scattered clumps of inflammatory cells in an otherwise innocuous parenchyma. Hepatitis (when inflammation in the liver prevails). 2. termed cirrhosis. Inherited hepatosis develops in storage diseases or enzymopathy. and a variety of drugs may incite a granulomatous reaction.  When massive hepatocellular necrosis occurs and leaves the connective tissue framework intact.  Accumulation of specific substances in viable hepatocytes. With disseminated candidal or bacterial infection. toxic. Fibrosis. c) Midzonal necrosis is a rare pattern. The massive necrosis is the most common acute hepatosis. Acquired hepatosis may be acute and chronic. Cirrhosis (when disregeneration is observed).  Inflammatory cells may be limited to the site of entry (portal tracts) or spill over into the parenchyma. expanding regions of the parenchyma are destroyed (geographic necrosis). 4. organisms. clear spaces. circulatory or traumatic agents. may be of particular diagnostic value.

I. the disease is more or less the same and can be divvied into four phases: 1. needle-stick accidents among health care workers. Morphological patterns of Acute Viral Hepatitis  Any one of the hepatotropic viruses can cause acute viral hepatitis. non-B (NANB) hepatitis virus involved chiefly in transfusion-related hepatitis. Etiology. small and large drop in the liver cells are observed. Stage of yellow degeneration. An incubation period carries on 15-45 days. poor hygiene and sanitation.115 Massive necrosis (toxic degeneration of the liver) Massive necrosis (toxic degeneration of the liver) is acute (rarely chronic) disease characterized by massive necrosis of the hepatocytes with development of the hepatic insufficiency. when liver becomes enlarged. Hepatitis may be mild to fulminant. A symptomatic preicteric phase. Progressive chronic disease ending in cirrhosis. 2. exceeding 50%. But in this pathologic agent has less toxicity and. Steatosis     It is a chronic disease. also tenned non-A. degenerative and necrotic changes in pancreas.dust-like. The cut surface is grey. The color is yellow. dense and yellow. Hepatitis C virus (HCV). 1. necrosis of the renal epithelium. It is most commonly caused by viral hepatitis. flabby. Microscopically fat degeneration. drug or mushroom toxicity. HAV does not cause chronic hepatitis. myocardial. The fatality rate associated with HAV is about 0. causing a parenterally transmitted disease that may become chronic. Morphology There are 2 stages in this hepatosis. Etiology of steatosis is similar to massive necrosis of the liver. An asymptomatic carrier state with or without progressive disease. HBV can produce: 1. blood products. HCV has a high rate of progression to chronic disease and eventual cirrhosis. Then it size increases. as a rule. 4. 3. Hepatitis C Virus (HCV). Microscopically . with fulminant disease somewhat more likely than with HBV alone. Fulminant hepatitis with massive liver necrosis. 5. Hepatitis B virus (HBV). it consistency becomes flabby. Transfusion. dialysis. numerous hemorrhages in the skin and mucous. Macroscopically the liver is red due to necrosis end autolysis of hepatocytes with appearance of plethoric blood vessels. and homosexual activity constitute primary risk categories for HBV. II. which is characterized by increase of fat amount in the cytoplasm of the hepatocytes. 2. 2. CNS are observed in the patients with massive necrosis of the liver. compensatory and adaptive processes are higher. This is called “goose” liver. Delta hepatitis virus (HDV) is acute coinfection by exposure to serum containing both HDV and HBV. An incubation period carries on 4 to 26 weeks. hyperplasia of lymph nodes and spleen. Fat drops are seen on the incision. and Hepatitis E Virus (HEV). IV. Hepatitis D Virus (HDV). chronicity rarely develops. Further more HBV plays an important role in the development of hepatocellular carcinoma.1%. Whatever the agent. . Jaundice. The disease occurs in epidemic form as well as sporadically. An incubation period. Stage of red degeneration is characterized by progressive reduction of liver size and mass. III. Hepatitis B Virus (HBV). intravenous drug abuse. Macroscopically the liver is enlarged. Hepatitis A virus (HAV) causing a fecally spread self-limiting disease. The spread is related to close personal contact such as in overcrowding. necrosis and autolysis of hepatocytes are observed. capsule is shrunken. Acute hepatitis. Viral hepatitis Viral hepatitis is reserved for infection of the liver caused by a small (but growing) group of viruses having a particular affinity for the liver: Hepatitis A Virus (HAV). Chronic nonprogressive hepatitis. Hepatitis A is responsible for 20-25% of clinical hepatitis in the developing countries of the world.

116 3. alpha-1-antitrypsin deficiency.  The portal tracts are usually infiltrated with a mixture of inflammatory cells.  Regenerating hepatocytes lack uniformity in size and are pale. chronic hepatitis has been classified according to the extent of inflammation: 1. the liver is slightly enlarged: more or less green depending on the phase of the acute disease and the degree of jaundice. the result of diminished numbers of cytoplasmic organelles. methotrexate). clumps.  Degenerated hepatocytes may also appear ballooned. or an entire lobule. in which inflammation is confined to the portal tracts. chronic alcoholism. Cholestasis is biliary stasis. or portal-to-central regions of adjacent lobules.  Kupffer cells and sinusoidal lining cells undergo hypertrophy and hyperplasia and are often laden with lipofuscin pigment owing to phagocytosis of hepatocellular debris. Therefore. Convalescence. 4. there are many other etiologies: Wilson‟s disease. is taken to mean chronic hepatitis.  An inconstant finding is bile stasis within the lobule. Chronic active hepatitis. Chronic lobular hepatitis. is the etiologic form of hepatitis. signifying a more severe form of acute hepatitis. Morphological patterns of Chronic Viral Hepatitis     Symptomatic. usually prominent feature of acute hepatitis. and therefore prognosis. forming poorly defined ductular structures (cholangioles). Regeneration. and autoimmunity. more or less radial array. the lobule remains somewhat disorganized because hepatocytes can proliferate faster than normal cord-sinusoid-cord relationships can be established. 3. particularly where adjacent hepatocytes have undergone necrosis.  In the recovery phase of acute hepatitis. necrosis. in which portal tract inflammation spills into the parenchyma and surrounds regions of necrotic hepatocytes. classification of chronic hepatitis strictly by histologic criteria is obsolete and should not be used.  The morphologic changes in acute viral hepatitis are virtually the same regardless of the causative agent and can be mimicked by drug reactions. Residual clumps of inflammatory cells may persist for some time.  Histologically the major findings are: Hepatocellular injury:  Necrosis of scattered hepatocytes.  Macrophages may phagocytize the necrotic hepatocytes. Although the hepatitis viruses are responsible for most cases of chronic hepatitis.  Confluent necrosis may lead to bridging necrosis connecting portal-to-portal. Disruption of lobular architecture by necrosis is called lobular disarry. or serologic evidence of continuing or relapsing hepatic disease for more than 6 months. Fatty change is unusual except with HCV. and regeneration of cells producing compression of the vascular sinusoids and loss of the normal. A symptomatic icteric phase. alpha-methyldopa. particularly in cases of HCV hepatitis. The bile duct epithelium may proliferate.  Grossly. Reactive changes in Kupffer’s cells. in which persistent inflammation is confined to the lobule. This is particularly . 2. Chronic persistent hepatitis. although histologic information may provide information helpful for patient management.  Lobular disarray results from the cellular swelling (ballooning). Inflammation is a characteristic. It is now apparent that the primary determinant of disease progression. and may accumulate clumps of lymphocytes and macrophages. central-tocentral.  Double and triple nuclei in regenerating cells are commonly observed.  Isolated liver cells or small cell clusters appear as eosinophilic rounded-up cells (apoptotic bodies. Councilman’s bodies). this infiltrate consists of lymphocytes with a touch of leucocytes and may spill over into the parenchyma. biochemical. drugs (isoniazid. optimally with histologically documented inflammation and necrosis. Since 1968.

2. and serologic observations. Laboratory studies may reveal prolongation of the prothrombin time and. in some instances. Conversely. results in cirrhosis. occasional plasma cells.117   important because therapy that is effective for one cause of chronic hepatitis may be ineffective. bridging necrosis may connect adjacent portal-portal. The likelihood of chronic hepatitis following acute viral infection can be summarized: 1. accompanied by hepatocyte regeneration. 5. or potentially detrimental. centralcentral. hence the facetious designation “transaminitis”. HCV: Develops in more than 50% of infected patients. hepatic tenderness. Chronic active (aggressive) hepatitis is defined as a progressive form of chronic necrotising and fibrosing disease involving portal tracts as well as hepatic parenchyma. and an occasional rare neutrophiles or eosinophiles. a more severe chronic hepatitis is the most frequent outcome of HDV superinfection. lymphoid aggregates in portal tracts and mild fatty change are seen in about 50% of cases. and occasional bouts of mild jaundice. it is frequently impossible to identify the etiology of chronic hepatitis on tissue samples.  Although piecemeal and bridging necrosis do not imply inevitable progression of disease. and mild splenomegaly. and apparently with HCV. the most common being spider angiomas. In patients with chronic HCV hepatitis.  There may be lobular inflammation with focal necrosis of hepatocytes.  There is absence of piecemeal necrosis. less common symptoms are malaise. of whom one-fourth progress to cirrhosis. in other forms of the disease. HEV: Does not produce chronic hepatitis. The aforementioned features are common to all forms of chronic hepatitis (viral or otherwise). Despite use of immunohistochemical techniques.  The lobular architecture of hepatic parenchyma is usually preserved.  There may be formation of lymphoid follicles. Microscopically:  The histologic hallmark of progressive disease is piecemeal necrosis. half of whom progresses to cirrhosis. and portal-central zones. consisting of lymphocytes. loss of appetite.  As with acute hepatitis. and mild elevations in alkaline phosphatase. continued loss of hepatocytes results in fibrous septum formation. Microscopically:  There is portal triad characterized by expansion of the portal tract by mononuclear inflammatory cells. . contributes significantly to the development of primary hepatocellular carcinoma. The diagnosis of chronic persistent hepatitis is confirmed by needle biopsy of the liver. Physical findings are few. so great reliance must be placed on clinical. The most common symptom is fatigue. In some patients. HBV: Develops in more than 90% of infected neonates and 5% of infected adults. “groundglass” hepatocytes are sometimes present in chronic HBV hepatitis. mild hepatomegaly. hyperglobulinemia. macrophages. virologic. The clinical features of chronic hepatitis      The clinical features of chronic hepatitis are extremely variable and are not predictive of outcome. hyperbilirubinemia. 4. with associated necrosis of hepatocytes in the limiting plate. which is invaluable in distinguishing it from more serious form of chronic active hepatitis. palmar erythema. HDV: Rare in acute HDV/HBV coinfection. the only signs of chronic disease are persistent elevations of serum transaminases. if any. Morphology The morphology of chronic hepatitis ranges from exceedingly mild to severe. HAV: Extremely rare. 3. Chronic hepatitis with HBV. to eventual cirrhosis. which. and bile duct damage is seen in more than 90%. where by the chronic inflammatory infiltrate spills out from portal tracts into adjacent parenchyma.

2. allergen.e.). 6. once developed. The major causes of death are hepatic insuffisiency and hepatic encephalopathy or massive hemorrhage from esophageal varicose and.. polyarteritis nodosa) or glomerulonephritis. The fibrosis. in those with long-standing HBV (particularly neonatal) or a HCV infection. i. Macronodular (the nodules are of variable size and are generally large than 3 mm in diameter). The nodules may vary from micronodules (less than 3 mm in diameter) to macronodules (3 mm to several centimeters in diameter). 4. focal injury with scarring does not constitute cirrhosis. Cryptogenic cirrhosis (10-15%). Cardiac cirrhosis. 2. 3. Micronodular (the nodules are usually regular and small. 3. 3. 2. Pigment cirrhosis in hemochromatosis (5%). Infectious (often viral). has no evidence of continuing hepatocellular necrosis and has sharply-defined nodules of surviving hepatic parenchyma without any significant inflammation. Mixed cirrhosis. and rarely in HCV. hepatocellular carcinoma. is generally irreversible. Types according to morphogenesis 1.118   Occasionally in cases of HBV. Cirrhosis of Liver Cirrhosis is the final stage of liver disease and is defined by three characteristics: 1. Toxic and toxic-allergic (Alcoholic cirrhosis. Metabolic-alimentary (Cirrhosis in Wilson‟s disease. Postnecrotic cirrhosis. . 60-70%. extending throughout the liver.). The parenchymal architecture of the liver is divided by interconnecting fibrous scars. a process that closely resembles chronic active hepatosis characterizes an active form. 2. Nodularity is requisite for the diagnosis and reflects the balance between regenerative activity and constrictive scarring. with formation of abnormal interconnections between vascular inflow and hepatic vein outflow. in the form of vasculitis (subcutaneous or visceral. Morphological patterns of cirrhosis . Each of these forms may have an active and inactive form: . the most common. Biliary cirrhosis (5-10%). Vascular architecture is recognized by parenchymal damage and scarring.Hepatocellular necrosis and inflammatory reaction. etc. 3. 5. less than 3 mm in diameter). Cirrhosis in α-l antitrypsin deficiency. 4. Several features should be understood: 1. The parenchymal injury and consequent fibrosis are diffuse. Parenchymal nodules are created by regeneration of hepatocytes. drugs.An inactive form. Classification Morphological types of cirrhosis 1. vise verse. Mixed (some part of the liver show micronodular appearance while other parts show macronodular pattern). Fibrosis is present in the form of delicate bands or broad scars replacing multiple adjacent lobules. 3. Etiologic types of cirrhosis 1. 2. etc. Portal (septical) cirrhosis. some regression has been observed in humans with treated schistosomiasis and hemochromatosis. immune-complex diseases may develop secondary to the presence of circulating antibody-antigen complexes.

or regeneration of the liver cells permits survival with little or no residual scarring. this disease causes chronic inflammation of intrahepatic bile ducts. In a small number of instances. Alternatively. Postnecrotic cirrhosis      This pattern of cirrhosis is characterized by irregularly sized nodules separated by variable but mostly broad scars.  The fibrous septa dividing the variable-sized nodules are generally thick. having distorted shape with irregular and coarse scars and nodules of varying size. readily misinterpreted as postnecrotic cirrhosis in the absence of a history of chronic alcoholism. with the peak incidence between 40 and 50 years. cirrhosis appears only late in the course. such as phosphorus. the features are following:  Abnormal lobular architecture can be identified and central veins are hard to find. Eventually active liver cell necrosis becomes inconspicuous. The onset is insidious. A single attack of massive hepatic necrosis only infrequently gives rise to postnecrotic cirrhosis because either it is fatal. Severe collapse may leave a shrunken liver less than 1 kg in size. usually presenting with pruritus. biochemical and morphological features of long-continued cholestasis of extrahepatic or intrahepatic origin. or a drug such as acetaminophen. The most common known cause is previous viral infection. Fatty degeneration may be present.119    Morphological changes of all types of cirrhosis are similar. Biliary cirrhosis Biliary cirrhosis is defined as a chronic disorder characterized by clinical. there is a well-documented history of acute liver damage caused by some hepatotoxin. Residua of portal tracts may be evident. there remains a large residual of uncertain origin. mushroom poisoning. carbon tetrachloride. Morphology        Typically some time after an acute event or following years of chronic hepatitis. in about 20 to 25% of cases it evolves from chronic HBV infection. granulomatous destruction of medium-sized intrahepatic bile ducts. the contribution of chronic HCV may be even greater. This is primarily a disease of middle-aged women.  Liver cells vary considerably in size and multiple large nuclei are common in regenerative nodules. There is primary and secondary biliary cirrhosis. in time. . Microscopically. Jaundice develops late in the course. Ultimately the diagnosis rests on excluding other bases for cirrhosis. progressive chronic hepatitis of any etiology inexorably transforms a more normalized liver into a patchwork of variably sized nodules alternating with broad septal scars. Macroscopically the liver is small. or alpha-methyldopa. Undoubtedly some cases represent end-stage alcoholic cirrhosis. The primary feature of this disease is a nonsuppurative. leading to their destruction and. bile stasis is variable. Often there is extensive proliferation of bile ductules derived from collapsed liver lobules. The cut surface shows scars and nodules varying in diameter from 3 mm to a few centimetres. Age of onset is between 20 and 80 years.  Active liver cell necrosis is observed. oxyphenisatin. Primary biliary cirrhosis (PBC)     Primary biliary cirrhosis (PBC) is autoimmune disorder focused on intralobular bile ducts and holangioles. cirrhosis. Fibrous septa contain prominent mononuclear inflammatory cell infiltrate even with follicles. After all these possibilities have been excluded. with a female-to-male predominance in excess of 6:1. Microscopically tubular architecture may be completely lost in the developing nodules and scar. the liver exhibits nodules of varying size (some several centimeters in diameter) and broad bands or areas of depressed scarring.

there is frequently a narrow zone of edema and ductular proliferation at the junction of parenchyma and septa. the liver is of yellow-green color and is accompanied by marked icteric discoloration of body tissues and fluids. Secondary bacterial infection ("ascending cholangitis") may contribute to the damage. the liver is hard. Affected portal tracts exhibit a dense infiltrate of lymphocytes (including lymphoid follicle formation). the end-stage picture may be difficult to distinguish from secondary biliary cirrhosis or the cirrhosis that follows chronic active hepatitis. with cytoplasmic and canalicular accumulation of bile. Stigmata of chronic liver disease are late features. other conditions include biliary atresia. Microscopically:  Large and small bile ducts are distended and frequently contain inspissated bile. Parenchymal holestasis may be present. holestasis is prominent. 3) Fibrosis. Hepatocyte loss. plasma cells. Retained bile leads to inflammation initiating periportal fibrosis and eventual cirrhosis. four histologic stages have described: 1) The duct lesion (granulomatous destruction of interlobular bile ducts). fibrosis. 4) Cirrhosis. however. malignancies of the biliary tree and head of the pancreas. causing destruction of adjacent hepatocytes (piecemeal necrosis). With time. enteric organisms such as coliforms and enterococci are common culprits. Macroscopically. bile stasis may become less conspicuous. and secondary obstructive changes develop. Historically. histiocytes. normal interlobular bile ducts become infrequent.  Portal tracts are interconnected by inflamed fibrous septa and appear edematous. The most common cause of obstruction is an impacted gallstone in the common bile duct. PBC is the prototype of all conditions leading to small-duct biliary fibrosis and cirrhosis. Initially portal tract inflammation may be marked and spill over into the parenchyma. Mallory bodies (alcoholic hyaline) may be present in hepatocytes adjacent to portal tracts.  Once the regenerative nodules of cirrhosis have formed. Macroscopically the liver does not at first appear abnormal. and a few eosinophils. ultimately liver weight is slightly decreased. . with a finely granular appearance. On cut surface. uniform micronodularity.  Ascending bacterial infection incites a supervening robust neutrophilic infiltration of bile ducts and cholangitic abscesses. Xanthomas and xanthelasmas arise as a result of cholesterol retention. Bile ducts are reduced. bile stasis stains the liver green. Secondary biliary cirrhosis       Develops with prolonged extrahepatic biliary tract obstruction. focal destruction of interlobular and septal bile ducts by granulomatous inflammation. With more global hepatic involvement. Liver weight is at first normal to increased (owing to inflammation). but as the disease progresses. The disease may be asymptomatic for years. and nodular regeneration lead to the gradual development of true cirrhosis. running its course over two or more decades.  Cholestatic features may be severe. extensive feathery degeneration of hepatocytes. inflammation decreases. Cardiac cirrhosis  Cardiac cirrhosis is uncommon complication of severe right-sided congestive heart failure of long-standing duration. In most cases. and the formation of bile lakes (see earlier discussion of cholestasis). granulomas and duct lesions become infrequent and are replaced by fibrous septa. similar to those seen in extrahepatic obstruction. named the florid duct lesion.120     Hepatomegaly is typical. culminating in a well developed. 2) Ductular proliferation with periportal hepatitis. The capsule remains smooth and glistening until a fine granularity appears. There is random. and strictures resulting from previous surgical procedures.

Regenerative activity of the entrapped parenchymal acini generates fairly uniformly sized “micronodules”. this lesion may smaller on long after cessation of alcohol intake. Although there is little or no fibrosis at the outset. Alcoholic hepatitis. 2. Microscopically. visible as eosinophilic cytoplasmic inclusions. greasy organ. the hepatic sinusoids are dilated and congested with hemorrhagic necrosis of centrolobular hepatocytes. Then fibrous strands radiating from the central veins are observed. Hepatic steatosis       Following even moderate intake of alcohol. This transformation is initially centrolobular. particularly those having Mallory bodies. Fat may be present or entirely absent. Of greatest impact. and is a soft. but in severe cases. single or scattered foci of cells undergo swelling (ballooning) and necrosis. Alcoholic liver disease Alcohol abuse constitutes the major form of liver disease in many countries. and sometimes less than 1 kg in weight. forms of liver disease: 1. . compressing and displacing the nucleus to the periphery of the hepatocyte. Alcoholic hepatitis Alcoholic hepatitis exhibits the following: Liver cell necrosis. Initially the developing fibrous septa are delicate and extend from central vein to portal regions as well as from portal tract to portal tract. nonfatty organ. the fatty change is completely reversible if there is further abstention from alcohol. Cirrhosis referred to as alcoholic liver disease. Over the span of years. Chronic alcohol consumption has a variety of adverse effects. With chronic intake of alcohol. yellow. scattered hepatocytes accumulate tangled skeins of cytokeratin intermediate filaments and other proteins. it is transformed into a brown. it may involve the entire lobule. fatty. tricuspid insufficiency or constrictive pericarditis. Deranged iron processing in the alcoholic typically leads to a modest accumulation of hemosiderin in hepatocytes and Kupffer‟s cells. small (microvesicular) lipid droplets accumulate in hepatocytes. The condition may resolve in the absence of further alcohol exposure or may lead to cirrhosis. more frequently in the centrolobular regions of the lobule. occasionally periportal fibrosis may predominate. Alcoholic hepatitis is almost always accompanied by a sinusoidal and perivenular fibrosis. fibrous tissue develops around the central veins and extends into the adjacent sinusoids. but there is significant risk of death with each bout. At first the cirrhotic liver is yellow-tan.  Fibrosis. albeit overlapping. The outcome is unpredictable. usually weighing more than 2 kg. Up to the time that fibrosis appears.121    The common causes culminating in cardiac cirrhosis are “cor pulmonale”. lipid accumulates to the point of creating large clear macrovesicular spaces. shrunken. and enlarged. up to 4 to 6 kg. Lymphocytes and macrophages also enter portal tracts and spill into the lobule. there are three distinctive. Cirrhosis may develop within 1 to 2 years in the setting of alcoholic hepatitis. 3. however.  Neutrophilic reaction. Neutrophils permeate the lobule and accumulate around degenerating liver cells.  Mallory bodies (alcoholic hyaline). particularly with repeated bouts of heavy alcohol intake. Potentially reversible. with continued alcohol abuse. The liver is often grossly enlarged.  Alcoholic cirrhosis       The final and irreversible form of alcoholic liver disease usually evolves slowly and insidiously. Hepatic steatosis.

Hepatorenal syndrome leading to renal failure may occur in late stages of cirrhosis.  Hepatic ehcephalopathy. Mallory bodies are only rarely evident at this stage. the nodularity becomes more prominent. 3. 5. 7. loses fat. leaving residual parenchymal nodules that protrude like “hobnails” from the surface of the liver (“Laennec‟s cirrhosis”). Cardiovascular complications such as atherosclerosis of coronaries and aorta and myocardial infarction are more frequent in these patients. Infections are more frequent in patients with cirrhosis due to impaired phagocytic activity of reticuloendothelial system. Accordingly. Complications of cirrhosis Complications of cirrhosis are subdivided into 2 groups: hepatic and non-hepatic I. They are usually formed in the gall bladder. both macroscopically and microscopically.  Gall stones usually of pigment type. the gallstones commonly contain cholesterol. testicular atrophy and impotence. Causes of death 1. end-stage alcoholic cirrhosis comes to resemble. age. Non-hepatic complication: 1. cholesterol. Further ischemic necrosis and fibrous obliteration of nodules eventually create broad expanses of tough. Hepatorenal syndrome. sex. Intercurrent infections. Hematological derangements such as bleeding disorders and anemia due to impaired hepatic synthesis of coagulation factors and hypoalbuminemia are present. scattered nodules may become quite large. diet and various other risk factors. but sometimes may develop within extrahepatic biliary passages. Hypertrophic osteoarthropathy. and shrinks progressively in size. pate scar tissue.122       With time. 2. 3. are seen twice more frequently in patients with cirrhosis than in general population. rectum. and rarely in the larger intrahepatic bile duct.  Steatorrhea due to reduced hepatic bile secretion. the liver becomes more fibrotic. Cholelitiasis (Gallstones)      Gallstones are formed from constituents of the bile (viz. the septa contain variable amounts of scattered lymphocytes and some reactive bile duct proliferation. The incidence of gallstones varies markedly in different geographic areas. Development of hepatocellular carcinoma. 4. whereas in cirrhotic women amenorrhoe is a frequent abnormality.  Congestive splenomegaly. bile pigments and calcium salts) along with other organic components. Bile stasis often develops. 8. 6. Hepatic complication:  Progressive hepatic insufficiency. By microscopy. and the liver is converted into a mixed micronodular and macronodular pattern. especially in alcoholic liver disease. Thus. Massive gastrointestinal hemorrhage from esophageal varice. bile pigment and calcium salts in varying proportions. 2.  The formation of portosystemic venous shunts through variceal chanells in the esophagus. and occasionally nodules more than 2 cm in diameter may develop. postnecrotic cirrhosis. 4. and periumbilical abdominal wall. Chronic relapsing pancreatitis. Hepatic coma. The mechanism of cholesterol gallstone formation or lithogenesis is determined by 3 major factors: . Endocrine disorders such as gynecomastia. II. Portal hypertension (increased resistance to portal flow) and its effects such as  Ascites. Parenchymal islands are engulfed by ever wider bands of fibrous tissue. As fibrous septa dissect and surround nodules. 5.  Development of hepatocellular carcinoma.

The lumen is filled with pus mixed with green bile. and gallbladder cancer. In majority of cases. may be observed: thickened and congested mucosa but occasionally mucosa may be totally destroyed. Based on the initiating mechanisms. biliary fistula. congestion and neutrophilic exudate. bums. Numerous complications develop in cholelithiasis. Cholecyscitis Cholecyscitis or inflammation of the gallbladder may be acute. The commonest location of impaction of a gallstone is in Hartman‟s pouch. consisting of lymphocytes. gallstone ileus. multiple injuries. The serosal surface is coated with fibrinous exudate with congestion and hemorrhages. either in pure form or in various combinations. or flattened and atrophied. severe sepsis. variable degree of chronic inflammatory reaction. Acute calculous cholecystitis. In general. They are cholecystitis. Macroscopically. supervenes. a variety of causes have been assigned such as previous nonbiliary surgery. thickened. the gall bladder is distended and tense. acute cholecystitis occurs in two types of situations acute calculous and acute acalculous cholecystitis. The wall of the gall bladder is thickened which on cut section is grey-white due to dense fibrosis or may be even calcified. The association of chronic cholecystitis with mixed and combined gallstones is virtually always present. diabetes mellitus. or acute superimposed on chronic. gallstones are formed most frequently in the gall bladder but may occur in exlrahepatic as well as intrahepatic biliary passages. choledocholithiasis. When obstruction of the cystic duct is complete. The remaining 10% cases of acute cholecystitis do not contain gallstones. There may be frank abscesses in the wall and gangrenous necrosis with rupture into the peritoneal cavity (gangrenous cholecystitis). The condition usually begins with obstruction. the two forms of acute cholecystitis are morphologically similar. the following signs. After that secondary bacterial infection. penetration of the mucosa deep into the wall of the gall bladder up td muscular layer to form Rokitansky-Aschoff sinuses. etc. 3) The hyperfunction of gallbladder. In such cases. acute cholecystitis is caused by obstruction in the neck of the gallbladder or in the cystic duct by a gallstone. a stone is generally impacted in the neck or in the cystic duct. gallstones contain cholesterol. acute cholecystitis is similar to acute appendicitis. Macroscopically. chronic. mucocele or hydrops of the gallbladder. Gallstones are of 3 major types: 1) Pure gallstones 2) Mixed gallstones 3) Combined gallstones. The mucosal folds may be intact.123    1) Namely supersaturation of bile with cholesterol. bile pigment and calcium carbonate. for instance E. the gall bladder is generally contracted but may be normal or enlarged. variable degree of fibrosis in the subserosal and subepithelial layers. Microscopically. plasma cells and macrophages. Microscopically. 2) Cholesterol nucleation. As stated before. Acute cholecystitis     In many ways. wall of the gall bladder shows marked inflammatory edema. . The lumen commonly contains multiple mixed stones or a combined stone. Morphology    Except for the presence or absence of calculi. the lumen is filled with purulent exudate and the condition is known as empyema of the gall bladder. followed by infection later.coli and Streptococcus facialis. Chronic Cholecystitis     Chronic cholecystitis is the commonest type of clinical gallbladder disease. present in the lamina propria and subserosal layer. The mucosa is red. In calculous cholecystitis. Types of gallstones.

The onset of acute pancreatitis is sudden. The severe form of the disease associated with macroscopic hemorrhages and fat necrosis in and around the pancreas is termed acute hemorrhage pancreatitis or acute pancreatic necrosis. Most cases of chronic pancreatitis are caused by the same factors as for acute pancreatitis. The basic alterations are proteolytic destruction of pancreatic substance. Systemic complications are chemical and bacterial peritonitis. necrosis of fat. and duodenal obstruction. . and acute cholecystitis. and acute renal failure. Later manifestations include associated diabetes mellitus and steatorrhea. certain drugs. and variable obstruction of pancreatic ducts of all sizes.124 Pancreatitis Pancreatitis is inflammation of the pancreas with acinic cell injury. blood-borne bacterial infection. Acute pancreatitis      Acute pancreatitis is an acute inflammation of the pancreas. to stones 1 cm to several centimetres in diameter. the gland is hard and exhibits foci of calcification and may developed pancreatic calculi. necrosis of blood vessels with subsequent hemorrhage. perforated peptic ulcer. 2. Macroscopically. The ductal epithelium may be atrophied or hyperplastic or may show squamous metaplasia. Etiology. endotoxic shock. These concretions vary from calculi invisible to the naked eye. Amorphous basophilic calcium precipitates may be visible within the necrotic focus. The two leading causes associated with acute pancreatitis are alcoholism and cholelithiasis. Complications A patient of acute pancreatitis who survives may develop a variety of systemic and local complications: 1. foci of pancreatic necrosis are blue-black hemorrhages and grey-white necrotic softening alternates with sprinkled foci of yellow-white. chalky fat necrosis. Grossly. occurring after a bout of alcohol or a heavy meal. ischemia. viral infections. vomiting and collapse and the condition must be differentiated from other diseases producing acute abdomen such as acute appendicitis. etc. reduced number and size of acini with relative sparing of the islets of Langerhans.  Most patients present with recurrent attacks of severe abdominal pain at intervals of months to years. both of which are implicated in more than 80% of cases. Chronic pancreatitis Chronic pancreatitis is the progressive destruction of the pancreas due to repeated mild and subclinical attack of acute pancreatitis. The condition occurs in adults between the age of 40 and 70 years and is commoner in females than in males. and an accompanying inflammatory reaction.  Weight loss and jaundice are often associated. pancreatic pseudocyst. A chronic inflammatory infiltrate around lobules and ducts is usually present. shock. The lesions have a macroscopic lobular distribution and may involve portions or the entire pancreas. Morphology     The morphology of acute pancreatic necrosis stems directly from the action of activated pancreatic enzymes that are released into the pancreatic substance. The patient presents with abdominal pain. Less common causes of acute pancreatitis include trauma. It is classified into acute and chronic forms both of which are two distinct entities.  Etiology. extension of inflammation from the adjacent tissues. Morphology      Chronic pancreatitis is distinguished by irregularly distributed fibrosis. Local complications are pancreatic abscess. giving rise to the term “chronic calcifying pancreatitis”.

Immune mechanisms A. Asymptomatic hematuria or proteinuria. hematuria. visceral epithelial. and lipiduria. endothelial. Chronic renal failure. lipoid nephrosis. pancreatic insufficiency with steatorrhea and malabsorption and formation of pancreatic pseudocysts. mild to moderate proteinuria. We can now turn to a brief description of the major renal syndromes: 1. diabetes mellitus. etc. 2. Urinary tract infection is characterized by bacteriuria and pyuria. 1. The nephrotic syndrome is characterized by heavy proteinuria. Protein plugs and calcified stones are rare. 2. Immune complex disease. Acute nephritic syndrome is a glomerular syndrome dominated by the acute inset of usually grossly visible hematuria (red blood cells in urine). More recently there has been evidence to suggest that cellmediated immune reactions in the form of delayed type hypersensitivity can cause glomerular injury. The infection may be symptomatic or asymptomatic. DISEASES OF KIDNEY AND URINARY TRACT Diseases of the kidney are characterized by the injury basic morphologic components: glomeruli. interstitial injury. the distribution of lesions is irregular. it is the classic presentation of acute poststreptococcal glomerulonephritis (GN). etc. amyloidosis. is usually manifestation of subtle or mild glomerular abnormalities. It can result from glomerular injury. hyperlipidemia.  The deposition of Ag-Ab complexes in glomeruli is a major mechanism of glomerular injury. and blood vessels.e. Acute renal failure is dominated by oliguria or anuria. Renal tubular defects are dominated by polyuria. 5.).  Immunologic mechanisms underlying glomerular injury are primarily antibody-mediated (immune-complex disease).125  With chronic ductal obstruction. or acute tubular necrosis. There are two basic mechanisms of glomerular injury: immune and nonimmune. mesangial. They are the result of either diseases directly affecting tubular structure or defects in specific tubular infection. nocturia.) Pathogenesis of glomerular injury The consequences of injury at different sites within the glomerulus can be assessed when compared with the normal physiologic role of the main cells involved. whether they are formed “in situ” with glomerular antigens or are trapped circulating complexes. Complications Last stage of chronic pancreatitis may be complicated by diabetes mellitus. and parietal epithelial cells as well as of the GBM. and hypertension. and it may affect the kidney or the bladder only. 4. 6. The clinical manifestations of renal diseases can be grouped into reasonably well-defined syndromes. and the ductal epithelium generally is less severely damaged. 3. tubules. with recent onset of azotemia. i. severe edema. Nephrolitiasis (renal stone) is manifested by renal colic. In secondary glomerular diseases the kidney is one of many organs and systems damaged by a systemic disease ( Systemic lupus erythematous. Antibody-mediated glomerular injury 1. Glomerular deposits are formed by one of the following two mechanisms: . The latter may be inheridited or acquired. interstitium. hypoalbuminuria. and recurrent stone formation Glomerular Diseases Glomerular injury is a major cause of renal disease and may be primary and secondary. 8. characterized by prolonged symptoms and signs of uremia. is the final result of all chronic renal diseases. Primary glomerular diseases are characterized by primary injury of the glomeruli (acute and chronic glomerulonephritis (GN). 7. and electrilyte disorders. or a combination of them.

e. 3. IgA nephropathy and some cases of rapidly progressive GN and focal GN. systemic hypertension. e. A few autoantibodies have been implicated in some patients of glomerulonephritis:  Anti-neutrophil cytoplasmic antibodies (ANCA). 2. Autoantibodies against endothelial antigens have been detected in circulation are several inflammatory vasculitis and glomerulonephritis. Nonimmune mechanisms Though most forms of GN are immunologically mediated.g. mononuclear phagocytes. mesangial cells.g. complement system. Metabolic glomerular injury. membranous GN. their presence in high concentrations for prolonged periods. C. 3. Secondary pathogenetic mechanisms Secondary pathogenetic mechanisms are a number of mediators of immunologic glomerular injury. viral and parasitic products and drugs.  The deposits in alternate pathway of the disease are characteristically electron-dense. such as: neutrophils. Immune complex GN is observed in the following diseases: 1.  Anti-GBM disease is classically characterized by homogeneous linear deposits of anti-GBM antibodies (mostly IgG. platelets. HenochSchonlein purpura and idiopathic mixed cryoglobulinemia. lectins. amyloidosis. DNA. e.  Anti-GBM disease is characteristically exemplified by glomerular injury in Goodpasture‟s syndrome. ANCA causes endothelial injury by generation of reactive oxygen radicals. Anti. or when host mechanisms fail to eliminate immune complexes. About half to two-third of the patients with renal lesions in Goodpasture‟s syndrome have pulmonary hemorrhage mediated by cross-reacting autoantibodies against alveolar basement membrane. 2. The antigenantibody complexes are trapped in the glomeruli where they produce glomerular injury after combining with complement.  Anti-endothelial cell antibodies (AECA). glomerular disease in SLE. e. The examples of planted nonglomerular antigens are cationic proteins. or when they possess properties that cause their binding to glomeruli.g.g. Circulating immune complexes cause glomerular damage under certain circumstances. rarely IgA and IgM) and complement (mainly C3) along the glomerular basement membrane. cryoglobulinaemia. a few examples by non-immunologic mechanisms are found: 1. diabetic nephropathy. Hemodynamic glomerular injury.g.g. particularly in cases with deficient immunoglobulins. in particular C3.  Circulating immune complex deposits.  Alternate pathway disease occurs in most cases of type II membranoproliferative GN. Other mechanisms of antibody-mediated injury. e. Alternative pathway disease. syphilis. and coagulation system. acute diffuse proliferative GN. 2. glomerular lesions in such cases are referred to as dense-deposit disease. IgA nephropathy and in SLE. 4.  Less than 5% cases of human GN are associated with anti-GBM antibodies. About 40% cases of rapidly progressive GN are deficient in immunoglobulins in glomeruli and are positive for ANCA against neutrophil cytoplasmic antigens in their circulation. membranoproliferative GN. Cell-mediated Glomerular Injury Recent evidence suggests that cell-mediated immune reactions in the form of delayed hypersensitivity may be involved in causing glomerular injury. some patients of rapidly progressive GN. a protein of group A streptococci).126  Local immune complex deposits. . Formation of glomerular deposits of immune complex “in situ” occurs as a result of combination of antibodies with autologous nonbasement membrane antigens or nonglomerular antigens planted on glomeruli. Systemic diseases. e. acute diffuse proliferative GN. bacterial products (e.GBM disease. Primary GN. hepatitis. Deposition diseases. The component of GBM acting as antigen appears to component of collagen IV of the basement membrane. Classic experimental model of “in situ” immune complex GN is Heymann nephritis.g. contributes to glomerular injury in the majority of forms of GN. malaria.  The complement system. B.

such as: arterial hypertension. hypernitrogenemia and uremia are presence. and mild to moderate hypertension. viral. Infectious diseases. The patient also commonly has proteinuria and edema. In morphological classification. According to the etiology it may be bacterial.  By immunofluorescence microscopy there are glandular deposits of IgG. relatively bloodness glomeruli.  Infiltration by leukocytes. According to topography: iner. disproteinemia. electron-dense deposits on the epithelial side of the membrane. Acute Glomerulonephritis      The first group of glomerular diseases are characterized anatomically by inflammatory alterations in the glomeruli and clinically by a complex of findings classically reffered to as the syndrome of acute nephritis. The acute nephritic syndrome may occur in such multisystem diseases as SLE and polyarteritis nodosa. According to the pathogenesis there are 2 types of glomeluronephritis: -immunoassociated and non-immunoassociated. Inherited glomerular diseases. oliguria. presumably representing the antigen-antibody . e. hypercellular. but adults of any age can be affected.5 to 12 monthes. involving mesangial cell proliferation and matrix deposition. glomeruli just visible as grey avascular dots. nail-patella syndrome. The classic diagnostic picture is one of enlarged. IgM. and the tubes often contain red cell coasts and may show evidence of degeneration. and intraglomerular coagulationcause the glomerulosclerosis. pale. amorphous. Duration of disease may 1. it is characteristic of acute proliferative GN and is an important component of crescentic GN. red cell casts in the urine. Principles of glomeluronephritis classification    Gomerulonephritis may be primary or secondary. chronic. HCV. and leukocytic infiltration obliterates the capillary lumen.  There may be interstitial edema and inflammation. HIV.  There is also swelling of endothelial cells. however. HBV. Typically. The mesangial response. The nephritic patient usually presents with hematuria. often having the appearance of “humps”. both neutrophils and monocytes. According to propagation: diffuse and local. propagation of pathological process are accounted: 1. that is. Alport‟s syndrome. unclear. hypotrophy of right heart. edema. According to character of inflammation: nonsuppurative exudative and proliferative. The most often the histological type is intracapilary proliferative GN:  Proliferation of endothelial and mesangial cells and.  According to the course GN may be classified into acute. These diseases destroy sufficient functioning nephrons. 3. topography.and extracapillary GN.  According to the histological pattern of damage seen on renal biopsy. e. they are often focal and sparse. character. In occurs most frequently in children of six to ten years of age. 5. It is infectious-allergic or unknown etiology disease with double nonsuppurative glomerulitis. azotemia. Although present.127 4. 2.g. Nonrenal features. swelling.  Special stains can demonstrate small deposites of fibrin within capillary lumina and mesangium. involving all lobules of all glomeruli. medullary rays congested. Adaptive changes in glomeruli to the increased workload cause epithelial and endothelial injury and resulten proteinuria. epithelial cells. sub-acute. The proliferation and leukocytes infiltration are diffuse. in many cases. Acute poststreptococcal glomerulonephritis       It usually appears 1 to 4 weeks after streptococcal infection of the pharynx or the skin.g. and C3 in the mesangium and along the basement membrane. cortex broad. and the combination of proliferation. without markings. Gross appearance: Kidney enlarged. hence knowledge of this aspect of histopathology is needed to understand disease. but these are not as several those encountered in the nephrotic syndrome. The characteristic electron microscopic findings are the discrete.

This syndrome may occur in the course of three broad disease groups: 1. Metabolic disorders (diabetes mellitus. is dominated by the formation of distinctive crescents. mercury). hence the term “membranous”. involving intrinsic glomerular antigens or endogenous and exogenous or planted antigens. diffuse thickening of the glomerular capillary wall. Systemic lupus erythematosus (SLE). Fibrin strands are prominent between the cellular layers in the crescents. Postinfectious rapidly progressive (crescentic) glomerulonephritis. Neutrophils and lymphocytes can be present. schistomiasis. diffuse or focal endothelial proliferation. progressive decline in renal function. It is characterized by the presence of electron-dense. however. Systemic diseases (SLE. In about 85% of patients. the condition is truly “idiopathic”. Infections (chronic hepatitis B. 4. 2. most crescents undergo sclerosis.  The histologic picture. the glomeruli may show focal necrosis. Idiopathic. captopril). MGN may occur in association with known disorders or etiologic agents. 3. These include the following: 1. 2.). 5. Morphology   By light microscopy. Drugs (penicillamine. particularly carcinoma of the lung and colon and melanoma. the latter having lost their foot processes. complicating acute GN. By electron microscopy the apparent thickening is caused by irregular dense deposits between the basement membrane and the overlying epithelial cells. immonoglobulin-containing deposits along the epithelial side of the basement membrane. 6. Rapidly progressive (crescentic) glomerulonephritis It is a syndrome characterized by the accumulation of cells in Bowman‟s space in the form of “crescents” accompanied by a rapid. Malignant epithelial tumors. but in all cases shows distinct ruptures in the GBM. polyarteritis nodosa.  Depending on the underlying cause. The crescents eventually obliterate Bowman‟s space and compress the glomerular tuft. 3. Goodpasture‟s syndrom.  The syndrome is characterized histologically by the accumulation of cells in Bowman‟s space in the form of “crescents”. Subendothelial and intramembranous deposits sometimes seen. The kidneys are enlarged and pale. Morphoplogy   According to histological picture there is extracapillary proliferative GN.128 complexes at the epithelial cell surface. which are formed by proliferation of parietal cells and by migration of monocytes and macrophages into Bowman‟s space. but welldeveloped cases show diffuse thickening of the capillary wall. malaria). are postulated to account for the subepithelial electron-dense deposits. Exposure to inorganic salts (gold.etc. Nephrotic syndrome Membranous glomerulonephritis (MGN)       It is a major cause of nephrotic syndrome in adults. usually resulting in irreversible renal failure in weeks or months. syphilis.  Electron microscopy may disclose subepithelial deposits in some cases. frequently with severe oliguria or anuria. thyroiditis). the glomeruli may appear normal by light microscopy.  In time. and there is often swelling of endothelial and mesangial cells. . In situ formation and deposition of circulating immune complexes. the glomeruli appear normal in the early stages of the disease or exhibit uniform. often with petechial hemorrhages on the cortical surfaces. Early in the disease.

so-called “mesangial interposition”. narrowing of the glomerular capillaries causes ischemic atrophy of the tubules and interstitial fibrosis. Morphology Primary MPGN is devided into two major types on the basis of distinct ultrastructural.  The hypercellularity is produced by proliferation of cells in the mesangium. Immunofluorescence shows no immune deposits. this group of disorders is characterized histologically by alteration in the basement membrane and proliferation of glomerular cells. their epithelium is swelling. Gross appearances (“big white kidneys”): kidneys enlarged.  This is caused by “splitting” of the basement membrane because of the inclusion within it of processes of mesangial cells extending into the peripheral capillary loops. often focally. less commonly postinfectious acute nephritis. these spikes thicken to produce dome-like protrusions and eventually close over the immune deposits. Like many other GN. Tubules are dilated. . flabby. conteining hyaline and fatty droplets.129      Basement membrane material is laid down between these deposits. appearing as irregular spikes protruding from the GMB. Because the proliferation is predominant in the mesangium.  The glomeruli are large and hypercellular. With progress of the disease. Proteinuria is usually selective and is associated with loss glomerular filtration (negative changes) and a hyperpermeable capillary wall. Others changes: protein and fatty droplets in the tubular epithelium and stroma. irregular membrane. burying them within a markedly thickened.  The glomerular capillary wall often shows a “double-contour” or “tram-track” appearance. atrophy. although infiltrating leukocytes and parietal epithelial crescents are present in many cases. Membranoproliferative glomerulonephritis (MPGN)    As the term implies. Immunofluorescence microscopy demonstrates that the granular deposits contain both immunoglobulins and complement. especially evident in silver or PAS stains. most evident in the peripheral capillary loops. and probably pathogenic findings. histologic MPGN either can be associated with other systemic disorders and known etiologic agents (secondary MPGN) or may be primary. yellow color. Foamy macrophages and giant cells form granulomas is association with cholesterol deposits. Patients have hematuria or proteinuria demonstrate a combined nephritic-nephrotic picture. Minimal change disease (MCD) (Lipoid nephrosis)      Nephrotic syndrom in children can be often. a frequently used synonym is mesangiocapillary GN. characterized by normal glomeruli on light microscopy but uniform and diffuse effacement of the foot processes of visceral epithelial cells on electronic microscopy. In time.  The glomeruli have a “lobular” appearance accentuated by the proliferating mesangial cells and increased mesangial matrix. Fatty degeneration. Morphology     GBM isn‟t changes. immunofluorescent. Etiology is unknown. This is often the late result of membranous or membranoproliferative GN. The most characteristic feature of this condition is the good response to corticosteroid therapy. necrobiosis.  Injury of tubular structures and stroma take place. Chronic glomerulonephritis (CGN)   CGN is the final stage of GN when sclerosis has eliminated many glomeruli and their associated tubules.  The GBM is clearly thickened. without known cause (idiopathic) in the kidney. desquamation in tubular epithelium take place.  By light microscopy both types are similar.

surgical. and pulmonary changes of diffuse alveolar damage often ascribed to uremia (uremic pneumonitis).130  At the final stage. 6. acquired cystic disease. capsule is adherent and strips with difficult. extensive deposition of calcium oxalate crystals in tubules and interstitium. Pieces of renal tissue adhere to stripped capsule.  Kidneys from the patients with end-stage disease on long-term dialysis exhibit a variety of so-called “dialysis changes” that are unrelated to the primary disease. and rarely anuria or polyuria. ARF is caused by: 1. 5. 2. Disseminated intravascular renal coagulation. 7. Etiopathogenesis Ischemia may result from following causes: Shock (post-traumatic. Patients dying with chronic GN also exhibit pathologic changes outside the kidney that are related to the uremic state and are also present in other forms of chronic renal failure. occurs due to hypoperfusion of the kidneys resulting in focal damage to the tubules. 3. Weight is 50 gm each. most obvious in glomerular tufts and tubular basement membranes.  Back-leak of tubular fluid into the interstitium. muscle disease or extreme muscular exertion (myoglobinuria nephrosis). uremic gastroenteritis. pelvis dilated and they‟re in an increasing peripelvic fat. proteoglycan-rich stroma. cortical surfaces. Acute tubular necrosis (ATN) ATN is characterized by destrucrion of renal tubular epithelial cells either from ischemia or nephrotoxins. coma. the cortex is thinned and irregular. Histological feature is nephrosclerosis. calcification. Acute tubular necrosis. Often clinically important. obstetrical and septic). On cut section. black-water fever (hemoglobinuric nephrosis).  These include arterial intimal thickening caused by accumulation of smooth muscle-like cells and a loose. Ischemic ATN is called tubulorrhectic ATN or shock kidney. In early cases. On section. the cortex is often widened and pale. Such kidneys are called “secondary shrinkage of kidneys. Severe glomerular disease. left ventricular hypertrophy due to hypertension. the glomeruli may still show evidence of the primary disease. Uremia. burns. Urinary obstructions. Massive infection.  Tubular obstruction by casts in the lumina or by interstitial edema. The pathogenetic mechanism of ischemic ATN is explained on the basis of:  Arteriolar vasoconstriction induced by renin-angiotensin system. Crush injuries. often accompanied by oliguria. Tubulopathy Acute renal failure Acute renal failure (ARF) is a syndrome associated with acute suppression of renal function.  Mismatched blood transfusions. Morphology  The kidneys are symmetrically contracted and have diffusely granular. 4. it is difficult to determine the etiology of the pathological lesion. and increased numbers or renal adenomas and borderline adenocarcinomas. while medulla is dark. Acute tubulointerstitial nephritis. secondary hyperparathyroidism with nephrocalcinosis and renal osteodystrophy. Non-traumatic rhabdomyolysis induced by alcohol. Organic vascular obstruction.    Morphology  The kidneys are enlarged and swollen. hypertensive cardiac failure or cerebral hemorrhage may cause death.  The glomerular histology depends on the stage of the disease. dehydration. these includes uremic pericarditis. .

3. carbon tetrachloride. kidneys are diffusely swollen and edematous. with removal of dead material by phagocytic cells. As tubules open up and glomerular blood flow increases. with salt and water overload. The recovery stage (Polyuric phase. The maintenance stage (Oliguric phase. The pathogenetic mechanism producing ARF in toxic ATN is in principle similar to that for ischemic ATN. Acute renal failure and oliguria. tubules or blood vessels. 2. injection or inhalation of a number of toxic agents.131  Predominant changes are seen in the tubules. Replacement of fluid and electrolytes is needed to compensate for excessive loss from urine. and other manifestations of uremia dominating this phase. b) The desquamated cells may undergo dystrophic calcification. Nephrotoxic ATN occurs as a result of direct damage to tubular cells by ingestion. rising blood urea nitrogens. Hypokalemia. acute and chronic conditions may produce tubulointerstitial nephritis. hyperkalemia and fluid overload in patients develop. b) Focal tubular necrosis at different points along the nephron.  Morphology   The kidneys are enlarged and swollen. 10-21 days) is ushered by a steady increase in urine volume that may reach up to 3 liters per day. e) Disruption of tubular basement membrane (tubulorrhexis). The clinical course of ATN may be devided into stages: 1. which is flat and thin with few mitoses. as well as in the form of casts in urine. Macroscopically. patients develop polyuria. such as sulfonamides. d) Eosinophilic hyaline casts or pigmented hemoglobin and myoglobin casts in the tubular lumina. lasting for about 36 hours. 2-9 days) is characterized by sustained decreases in urine output to between 40 to 400 ml per day. the features are as follows: a) Epithelial cells of mainly proximal convoluted tubules are necrotic and desquamated into the tubular lumina. Regeneration of renal tubular epithelium takes place. The initiating stage (shock). Etiopathogenesis The toxic agents causing toxic ATN are: General poisons such as mercuric chloride. It is characterized by ischemic cortex and congestion of pyramids. ethylene glycol. hyperkaliemia. or obstetric event in the ischemic form of ATN. Tubular changes are as follows: a) Dilatation of the proximal and distal convoluted tubules.  Heavy metals (mercury. the cortex is pale. salicylates. cephalosporin). becomes a clinical problem. . On cut section. certain antibiotics (gentamycin. is dominated by the inciting medical. Tubulointerstitial Disease The term tubulointerstitial nephritis is used for inflammatory process that predominantly involves the renal interstitial tissue and is usually accompanied by some degree of tubular damage. surgical. while the medulla is slightly darker than normal. A number of bacterial and non-bacterial. barbiturates. This is because the regenerated tubular cells are undifferentiated and have not developed the specializations necessary for resorption of electrolytes and water. lead. anaesthetic agents (methoxyflurane. phosphorus and gold). rather than hyperkalemia. There is blockage of renal tubules by necrotic cells. halothane). d) The regenerating epithelium. The prognosis of ATN depends on the clinical setting surrounding its development. In mercuric chloride poisoning. The term interstitial nephritis is reserved for those cases where there is no primary involvement of glomeruli. metabolic acidosis. Interstitium shows edema and mild chronic inflammatory cell infiltrate. while glomeruli are normal.  Radiographic contrast material. It stage may be fatal.  Drugs. c) Flattened epithelium lining the tubules. may be seen lining the tubular basement membrane. mushrooms and insecticides. arsenic. In general it involves the segment of tubule diffusely. and a secondary reduction in glomerular blood flow (caused by arteriolar constriction) reduces glomerular filtration. c) Tubular basement membrane is generally intact.

which are usually spherical. 2. acute pyelonephritis has an acute onset with chills. UTIs are extremely common disorders. 1. intrestitium. Str. fecalis etc. Macroscopically. Etiopathogenesis     The dominant etiologic agents are the gram-negative bacilli that are normal inhabitants of the intestinal tract: E. At the acute phase of PN. Papillary necrosis is seen mainly in diabetics and in those with urinary tract obstruction. The neutrophilic infiltration is replaced by macrophages. after the capsule has been stripped away. Perinephric abscess implies extension of suppurative inflammation through the renal capsule into the perinephric tissue. In most patients with UTI. Three complications of acute PN are encountered in special circumstances. pus cells and pus cell casts in the urinary sediment. This is thus a form of endogenous infection. The term urinary tract infection (UTI) implies involvement of either the bladder (cystitis) or the kidney and their collecting system (pyelonephritis). Chronic PN is a more complex disorder: bacterial infection plays a dominant role. . Glomeruli usually unaffected. The pelvicalyceal mucosa is hyperemic or covered with a fibrinopurulent exudate. b) From the lower urinary tract (ascending infection). Papillary necrosis is usually bilateral. obstruction) are involved in its pathogenesis. diabetes mellitus acute PN may be more serious. In the medulla the abscesses tend to be in the form of yellowish white linear streaks that converge on the papilla. In the presence of unrelieved urinary obstruction. the infecting organisms are derived from the patient‟s own fecal flora. but may be unilateral. Clinical features. plasma cells. and (later) lymphocytes. it is incompetence of the vesicoureteral orifice that allows bacteria to ascend the ureter into the pelvis. 3. healing occurs. under 2 mm in diameter. and deformation of the underlying calyx and pelvis. Acute Pyelonephritis Morphology        The hallmarks of acute PN are patchy interstitial suppurative inflammation and tubular necrosis. leading to repeated septicemic episodes. fibrosis. Pyonephrosis is seen when there is total or almost complete obstruction. It occurs in two forms: 1. Acute PN is acute pyogenic infection. There are two routs by which bacteria can reach the kidneys: a) Through the bloodstream (hematogenous). the kidneys show variable numbers of small. other tubules filled by puss cells. loin pain. Uncomplicated acute PN usually follows a benign course. Histologically: the neutrophilic infiltration is limited to the interstitial tissue. the cortical abscesses are often most prominent on the sub-capsular surface. fever. particularly when it is high in the urinary tract (pelvis filled with puss). 2. dysuria and frequency of micturition.132 Pyelonephritis (PN) PN is a renal disorder affecting tubules. lumbar tenderness. yellowish white cortical abscesses. The pyelonephritic scar is almost always associated with inflammation. and are sometimes surrounded by a zone of hyperemia. Klebsiella and Enterobacter). Chronic Pyelonephritis (CPN) Chronic PN is a chronic tubulointerstitial renal disorder in which chronic tubulointerstitial inflammation and renal scarring are associated with pathologic involvement of the calyces and pelvis. and renal pelvis and is one of the most common diseases of the kidney. Classically. Although obstruction is an important predisposing factor in the pathogenesis of ascending infection. Some tubules destroyed: abscesses formed. or both. Urine will show bacteria. and the symptoms disappear within a few days after the institution of appropriate antibiotic therapy. but other factors (vesicoureteral reflux. The inflammatory foci are eventually replaced by scars.coli (Proteus.

calculi). which are normally in the large bowel. extrinsic compression). in which the kidneys are diffusely and symmetrically scarred. because they have a short urethra. Interstitium. The microscopic changes involve predominantly tubules and interstitium. and bacteriuria. urethral valves. Glomeruli. . or dilatation. Vesicoureteric reflux is particularly common in children. Recurrent episodes of such obstruction and infection result in renal damage and scarring. Morphology     The pelvicalyceal system is dark reddish brown as a result of acute inflammation of the usually smooth creamy mucosal lining due to bacterial infection. There is often periglomerular fibrosis. Chronic obstructive PN may be insidious in onset or may present the clinical manifestations of acute recurrent PN with back pain. urethra (prostatic hyperplasia or carcinoma. Infections of the lower urinary tract     Infections in the lower urinary tract are predisposed by obstruction and stasis. tumors). may occur at any place in the tract: renal pelvis (calculi. lower urinary tract infection is usually associated with structural abnormalities of the lower urinary tract and stasis due to obstruction. coli and Proteus. tumor. Pelvicalyceal system. due to congenital absence or shortening of the intravesical portion of the ureter so that ureter is not compressed during the act of micturition. bladder (tumor. ureter (calculi. Xanthogranulomatous pyelonephritis is an uncommon variant characterised by collection of foamy macrophages admixed with other inflammatory cells and giant cells. women are particularly prone to developing ascending infections. extrinsic compression -pregnancy. if bilateral. Reflux of urine from the bladder into one or both the ureters during micturition is the major cause of chronic pyelonephritis. fibrosis). The kidneys are usually small and contracted (weighing less than 100 gm) showing unequal reduction. pelviureteric junction (stricture. Dilated tubules may be filled with colloid crystals. In men. The renal pelvis and calyces are dilated. the involvement is asymmetric. In advanced cases. This contrasts with chronic glomerulonephritis. plasma cells and macrophages with pronounced interstitial fibrosis. urethral stricture). Obstruction of the drainage of urine from the kidney causes hydronephrosis. which are eventually followed by damage to the kidney and scar formation. Reflux results in increase in pressure in the renal pelvis so that the urine is forced into renal tubules.  Obstructive pyelonephritis. Clinical features. Chronic pyelonephritis often has an insidious onset. Blood vessels. The patients present with clinical picture of chronic renal failure or with symptoms of hypertension. Obstruction. E. Blood vessels entrapped in the scarred areas show obliterative endarteritis. the capsule can be stripped off with difficulty due to adherence to scars. chiefly composed of lymphocytes. And show marked chronic inflammation and fibrosis. The tubules show atrophy in some areas and hypertrophy in others. Diabetes mellitus also predisposes to infection. Lower urinary tract infection is usually due to Gram-negative coliform bacilli. The surface of the kidney is irregularly scarred. especially in girls. calculi. one of the most important consequences of disease of the lower urinary tract. there may be hyalinisation of glomeruli. There is chronic interstitial inflammatory reaction. producing thyroidisation of tubules (thyroidlike). Obstruction to the outflow of urine at different levels predisposes the kidney to infection. fever.133 Etiopathogenesis Two types of chronic pyelonephritis are described: Reflux nephropathy. frequent pyuria. There is generally dilatation of pelvis and blunted calyces. e. The kidney is also congested and some small scattered abscesses are present in the cortex and medulla (acute pyelonephritis).g.  Morphology          Gross examination.

This predisposes to development of out pouching of the bladder mucosa (diverticulae). the renal parenchyma becomes severely atrophic and renal function is permanently impaired. c) Extramural. However. prostrate. They may be pure stones of calcium oxalate (50%) or calcium phosphate (5%). a calculus in the ureter or renal pelvis. e. Unilateral hydronephrosis. Deposits are formed in the lymphatic vessels of the renal papillae and are extruted into the renal pelvis.g. if the obstruction is relieved. obstruction of upper part of ureter by inferior renal artery or vein. Complications: pyelonephtitis. function returns to normal.g. renal. Types of Urinary Calculi There are 4 main types of urinary calculi: 1) Calcium stones. neoplasm of ureter or bladder. pressure on ureter from outside such as carcinoma cervix. 4) Cystine stones. The causes are: a) Intraluminal. This is generally the result of some form of urethral obstruction but can occur from the various causes listed above if the lesions involve both sides. trauma. or mixture of calcium oxalate. Urolithiasis    Urolithiasis or formation of urinary calculi at any level of the urinary tract is a common condition. Uric acid stones are smooth. Hydroureter nearly always accompanies hydronephrosis Hydronephrosis may be unilateral or bilateral. Bilateral hydronephrosis. smooth and often multiple. atresia of the urethral meatus. 2. often called struvite. b) Intramural. hard and often multiple. Precipitates form in the collecting tubules and pass into renal pelvis where they enlarge. yellowish-brown. Two suggestions have been made: 1. a) Congenital. with progressive dilatation of the renal pelvicalyceal system. 3) Uric acid stones. Urinary tract obstruction also predisposes to infection and stone formation. They are yellowish and waxy.134    If obstruction occurs in the urethra. hydronephrosis. the bladder develops dilatation and secondary hypertrophy of muscle in its wall. inflammatory stricture. colon or cecum and retroperitoneal fibrosis. termed hydronephrosis.g. Renal calculi are characterized clinically by colicky pain (renal colic) as they pass down along the ureter and manifest by hematuria. glomerular hyalinization. there is dilatation of the ureter (megaureter). If obstruction occurs in a ureter. As an end-stage. congenital PUJ obstruction. congenital posterior urethral valve. e. 2) Mixed (Struvite) stones. Fluid entering the collecting ducts cannot empty into the renal pelvis and there is intrarenal resorption of fluid. Uric acid calculi are radiolucent unlike radio-opaque calcium stones.g. there is atrophy of renal tubules. hemorrhage. Calcium stones are the most common comprising about 75% of all urinary calculi. atresia of ureter. rectum. e. This occurs due to some form of ureteral obstruction at the level of periureteric junction (PUJ). Cystine stones are small. At this stage. rounded. if obstruction persists. They are seen in heritable tubular transport defects causing cystinuria. . Sites of formation. “'Staghorn stone” which is a large. About 15% of urinary calculi are made of magnesiumammonium-calcium phosphate. It is estimated that approximately 2% of the population experiences renal stone disease at sometime in their life with male-female ratio of 2:1. solitary stone that takes the shape of the renal pelvis where it is often formed is an example of struvite stone. Hydronephrosis      Hydronephrosis is the term used for dilatation of renal pelvis and calyces due to partial or intermittent obstruction to the outflow of urine. e. and fibrosis.

hemorrhagic erosions and ulcer in mucosa). the replacement and compression of functioning renal parenchyma by the cysts leads to slowly progressive impairment of renal function. the dilated pelvi-calyceal system extends deep into the renal cortex so that a thin rim of renal cortex is stretched over the dilated calcyes and the external surface assumes tabulated appearance. Importantly. Hemorrhagic syndrome (petechias. which is characterised by 1. leading to bloodstained contents. Hyperkaliemia. Cysts develop and progressively enlarge over a number of' years. Infantile polycystic disease is uncommon and is encountered at birth. but remain asymptomatic until the number and size of the cysts is so great that the patient becomes aware of abdominal masses. and organic acids). Acquired cystic disease is seen in kidneys left in situ while patients are treated by dialysis or transplantation for chronic renal failure. Fibrinous inflammation: . There is an association with berry aneurysms of the cerebral arteries. Uremia is final stage of chronic renal failure. Increasingly. but may rarely become infected or develop hemorrhage. Initially. with family screening and ultrasound examination. some of which produce renal failure by causing disturbance of renal structure. Arterial hypertension. phosphates. with development of hypertension. Hemorrhage into cysts is common. At about the same time. 8. inflammatory or traumatic urethral stricture and phimosis. watery fluid and have a smooth lining. and patients develop chronic renal failure and hypertension. with compression of the lungs due to massive enlargement of the kidneys. Cystic disease of the kidney          There are several cystic diseases of the kidney. 7. some conditions are heritable. 4. disease is detected in childhood. This advanced stage is called as intrarenal hydronephrosis. 6. Metabolic acidosis (accumulation of sulphates. They are widely held to be acquired abnormalities. 3. e.g. Simple cysts may be single or multiple and vary in size. Children develop severe renal failure. generally becoming clinically manifest in adult life. The wall of hydronephrotic sac is thickened due to fibrous scarring and chronic inflammatory cell infiltrate. 5. Morphology     The kidneys may have moderate to marked enlargement. Eventually. Adult polycystic disease is inherited in an autosomal dominant trait. prostatic carcinoma and prostatitis. Infections are common and will in turn affect renal function. Anemia. incidence increasing with age. Simple renal cysts are the most common form of renal cystic disease and must be distinguished from the congenital types discussed above. prostatic enlargement. Uremia is a syndrome encompassing a group of clinical and biochemical sings derived essentially from the retention of waste products and the failure to control fluid and electrolyte balance. Depression of immunological reaction. Patients with adult-type polycystic renal disease may also develop cysts in the liver. lung and pancreas. The kidney is converted into a mass of large cysts. predisposes to intracranial hemorrhage. bladder neck stenosis. 2. generally being no larger than 5-6 cm. bladder tumor involving ureteric orifices. there is extrarenal hydronephrosis characterised by dilatation of renal pelvis medially in the form of a sac. They contain clear.135 b) Acquired. which. Chronic renal failure    Nephrosclerosis is morphologic basis of chronic renal failure. Hypernitrogenemia. hypercalcemia. They have no effect on renal function.

c) Uremic gastritis. CIN 1 or mild dysplasia: cells of basal third have high nucleocytoplasmic ratio and pleomorphic nuclei. GENITAL TPACT DISEASES Diseases of Cervix    The cervix is an important site of pathology. The prognosis of final stage renal failure has been greatly improved by dialysis. colitis. Leukoplakia may develop (it means the white patches of hyperkeratosis). in pregnancy. Some of these microorganisms are sexually transmitted. CIN 3 or severe dysplasia or cancer in situ: almost complete loss of stratification. and the endocervical canal is covered by mucus-secreting columnar epithelium. such as residual fragments of tampons and pessaries. The term “cervical ectopia” is preffered. Dysplasia Dysplasia refers as cervical intraepithelial neoplasia (CIN) and it has 3 grades of differentiation: 1. d) Edema of lungs. Cervicitis      Cervicitis may be specific and non-specific. the junction between the squamous and columnar epithelium migrates into the convexity of the ectocervix. Since biopsy samples from the cervix frequently exhibit some degree of nonspecific chronic inflammation. 2. whereas others may be introduced by foreign bodies. less commonly. loss of polarity of the cells. enteritis. hormonal stimulation.136  a) Fibrinous pericarditis (“cor vilosum”). Zone transformation is dilated. and. Due to impairment of differentiations the dysplasia can take place. or Enterococcus. particularly in women of reproductive age. particulary Streptococcus. Purulent inflammation is a clinical sign of acute cervicitis. Diseases of Endometrium . b) “Uremic pneumonitis” with pleural exudates. then back into the endocervical canal. At various stages in a woman‟s reproductive life. The ectocervix is covered by squamous epithelium. Healing endocervicosis is characterized by recovery of normal structure of ectocervix or formation of Naboti‟s cysts. which shows glandular down growth. The inflamed cervix becomes congested and edematous. Acute and chronic cervicitis results from infection by any number of microorganisms. staphylococcus. variation in nuclear size with increase in nuclear/cytoplasmic ratio and mitotic figures. Progressive endocervicosis is characterised by proliferation of reserve cells and presence of the various size glands. 3. presence of the cervical glands in ectocervix and papillary formation. 3. Cervical erosion (endocervicosis)    It represents an unfolding and eversion of the distal endocervix into an ectocervix. Neisseria gonorrhoeae and Chlamydia trachomatis. According to duration the endocervicosis classified: 1. Etiology: increased uterine bulk. This squamocolumnar junction is the seat of most of the epithelial diseases that occur in the cervix. the diagnosis of chronic cervicitis should be made only when numerous lymphoid cells are present. CIN 2 or moderate dysplasia: basal cells occupy lower half of squamous epithelium. Simple endocervicosis is characterized by metaplasia of the squamous epithelium into columnar epithelium without proliferation of reserve cells. renal transplantation. 2.

hyperplasia. Abnormalities of the Normal Menstrual Cycle    Dysfunctional bleeding may also be associated with abnormalities of the normal menstrual cycle. The endometrium. or tuberculosis. which in turn leads to stasis. It is one of the most common gynecologic disorders of women of reproductive age. or both. but is also found in women who are being investigated for infertility. Endometritis Acute endometritis        This is almost confined to infection associated with partirition and abortion. Long-standing pyometra may be associated with the development of squamous cell cancer of the endometrium. Curettage is both diagnostic and curative because it removes the necrotic tissue that serves as the nidus of infection. Ovulatory oligomenorrhea (cycle longer than 45 days) is almost always due to a long follicular phase and may be the prelude to ovarian failure. Clinically. but one that is still poorly understood. in which cycles are less than 18 days in length. parametritis. and hemorrhage. subsequent tubal blockage and infertility. Pyometra. patients usually complain of bleeding. pelvic inflammatory disease. salpingitis. coliform organisms and proteus are usual. intrauterine contraceptive devices (IUD) use. and complications of intrauterine or ectopic pregnancy. is caused by short follicular phases (seen generally in adolescence) or short luteal phases (inadequate luteal phase). peritonitis. which results in loss of fluid from the stroma and hence loss of vascular support. Presence of polymorphonuclear leukocytes. The vascular collapse leads to compression of the vessels. fails to proceed through the normal secretory phase. infarction. such as a tumor or scarring from surgical treatment (conization) of the cervix.137 Dysfunctional Bleeding       Dysfunctional uterine bleeding is denned as abnormal bleeding in the absence of an organic lesion of the endometrium. Ovulatory polymenorrhea. Complications may follow endometritis: myometritis. The bleeding may be due to anovulatory cycles related to excessive and prolonged estrogenic stimulation. Suppurative inflammation is usual. Anovulatory Bleeding     Anovulatory bleeding is the most common form of dysfunctional uterine bleeding. particularly during adolescence and the climacteric period. A mixed bacterial flora. pyococci. . pelvic pain. is associated with any lesion that causes cervical stenosis. and retained products of conception after an abortion or delivery. pus in the endometrial cavity. thrombosis. a corpus luteum does not develop and progesterone is not secreted. Anovulatory bleeding is caused by a fall in estrogen levels. and an abnormal menstrual cycle results. Examples of organic disorders are carcinoma. endometritis. Without ovulation. Chronic endometritis may be caused by gonococcal or chlamydial infection. The latter may be due to defects in factors that maintain the corpus lutein. menstrual irregularities. On microscopic examination the glands are disordered and appear crowded because of severe stromal necrosis and collapse of the proliferative endometrium. results when an infection ascends from the cervix. therefore. Chronic endometritis    Chronic endometritis is usually associated with recent gestation. polyps. Organic lesions of the uterus must be excluded before the diagnosis of dysfunctional bleeding can be made. It is believed that estrogen maintains the stromal fluid turgescence that supports the blood vessels.

Typical locations for endometriosis may include: ovaries. Such areas of endometriosis can be seen and obliterated by cauterization via laparoscopy. or menometrorrhagia. Multiple layers of tall columnar epithelial cells with large nuclei. Simple hyperplasia (cystic glandular hyperplasia) is characterised by the presence of large and cystically dilated. Grossly. prominent nuclei. The acute episodes. which are lined by atrophic epithelium. Acute Salpingitis The host responds with a brisk granulocytic infiltrate and vascular engorgement. particularly those associated with chlamydial infection. It is classified into following 3 types: 1. varying-sized glands. Histologically: foci of endometrial glands and stroma. the tube distends and pyosalpinx develops. irregular and hyperchromic nuclei. but are not thought to be premalignant. Atypical hyperplasia (complex hyperplasia with atypia) is characterised by the presence of atypical cells in the hyperplastic epithelium. coli. Diseases of Fallopian tubes    Acute and chronic salpingitis usually results from an ascending infection from the lower genital tract. fallopian tubes and laparotomy scars. menorrhagia (excessive bleeding with menstrual periods). Endometriosis      When endometrial glands and stroma are found outside the uterus. in areas of endometriosis the blood is darker and gives the small foci of endometriosis the gross appearance of "powder burns". old or new hemorrhage. uterine ligaments. Adenomatous hyperplasia (complex hyperplasia without atypia). the condition is known as endometriosis. 2. line the glands and there is no atypia. may be asymptomatic. Hyperplasia of endometrium Endometrial hyperplasia usually results with conditions of prolonged estrogen excess and can lead to metrorrhagia (uterine bleeding at irregular intervals). even when just a few foci are present. . Complications may be caused by either destruction of epithelium or deposition of fibrin on the mucosal plicae. The most common causative organisms are E. Clostridia perfringens and various other anaerobes are less commonly encountered. The glands are enlarged and irregular with columnar cells that have some atypia (loss polarity. Sometimes the old dark brown blood collects over time from repeated hemorrhage in a cystic space in the ovary and produces a so-called “chocolate cyst” (endometriotic cyst). Endometriosis may even be found at more distant locations such as appendix and vagina. A fallopian tube damaged by prior infection is particularly susceptible to reinfection. which have not lost basal polarity. Chlamydia. It can be very disabling and painful. hemosiderin-laden macrophages and surrounding zone of inflammation and fibrosis. and Mycoplasma. 3. Up to 10% of women may have this condition. Chronic Salpingitis    Chronic salpingitis usually results from repeated episodes of acute salpingitis. and edema of the involved tubal layers ensues. glands small and infrequent. rectovaginal septum. This shows distinct proliferative pattern. Adenomatous hyperplasia is premalignant. and altered nucleocytoplasmic ratio). exhibit variation in size and are irregular in shape. The glands are increased in number. large size. pelvic peritoneum. N. Simple endometrial hyperplasias can cause bleeding. As the lumen fills with granulocytes. the fibrin bridges cause the plicae to adhere to one another. epithelium atrophied. gonorrheae.138  Histologically: stroma infiltrated by plasma cells and lymphocytes.

oligomenorrhea. fibrous adhesions (“violin string” adhesions). the adhesions may be dense and the fimbria adhere to each other to form a blunted. resulting in menstrual irregularity. up to 1 cm in diameter. filled with clear fluid. Follicilar cysts are cysts arising from Graafian follicles and are lined by granulosa cells.139     Fibrinous adhesions between the serosa and surrounding peritoneal surfaces may organize into thin. with an outer coat of thecal cells. They filled with clear serous fluid and may attain a diameter up to 2 sm. 3. In severe chronic salpingitis. leaving cysts surrounded by luteinised tissue. 4. low level of progesteron with high levels of circulating androgen produced by the ovary. The outer cortex is thick and fibrous. 2. Because of destruction of the tubal epithelium and fibrosis.  Histologically.g. Multiple follicular cysts. Theca lutein cysts are usually seen as multiple bilateral cysts. Patients have a persistent anovulatory state. 1. They are grey-white color and studded with multiple small bluish cysts just beneath the cortex. They are caused by high levels of gonadotropin. They may be single or multiple. hirsutism. chronic salpingitis may lead to infertility and ectopic pregnancy. There is continued production of progesterone. usually small. Luteal cysts are cysts from which the granulosa cells have disappeared. are associated with endometrial hyperplasia. . high level of estrogen. in hydatidiform mole and drug treatment). with a thick. The subcortical cysts are lined by prominent luteinised theca cells and represent follicles in various stages of maturation but there is no evidence of corpus lutein. yellow lining of luteinized granulosa cells. The high estrogen levels may cause endometrial hyperplasia and increase the risk of development of endometrial carcinoma.  The ovaries are usually involved bilaterally and are at least twice the size of the normal ovary. and infertility. Polycystic ovary disease (Stein-Leventhal Syndrome) is associated with obesity. clubbed end.  The pathogenesis of this syndrome is still uncertain. anovulation. The consequence of the blocked lumen may be a hydrosalpinx or pyosalpinx. Ovarian involvement leads to the formation of a tubo-ovarian abscess. which precipitates follicle development (e. Cysts are typically 2-3 cm in diameter. Diseases of Ovaries Ovarian changes of functional origin.

and. and previous surgery.  Ovarian pregnancy is presumed to result from the rare fertilization and trapping of the ovum within the follicle just at the time of its rupture. proteinuria and peripheral edema. A feature of pre-eclampsia is reduced placental blood flow. Because the tubal mucosa has a limited ability to undergo decidualization. the wall usually ruptures by the 12th week of gestation. Rupture into the lumen of the tube and leakage into perinatal cavity (tubal abortion). Exceedingly rarely the whole pregnancy – ovum and placental tissue – aborts into peritoneal cavity where it reimplants. 2. severe hypertension and intravascular coagulation occur with development of cerebral ischemia and fits. endothelial cells become swollen. with deposition of fibrin in glomeruli. and there is proteinuria and severe peripheral edema. interstitial implantation and tubal wall). with increased risk of perinatal mortality. primigravidae and women over the age of 35 years. gestational choriocarcinoma. Over 95% occur in the tube (ampullary implantation.140 Obstetric pathology Pre-eclampsia and eclampsia         Pre-eclamptic toxemia syndrome is characterised by hypertension. invasive mole. and placental site trophoblastic tumor.  Abdominal pregnancies may develop when the fertilized ovum drops out of the fimbriated end of the tube. in women fitted with intrauterine contraceptive devices. amniotic sac. Complications and causes of death: patients develop disseminated intravascular coagulation. Other factors are peritubal adhesions owing to appendicitis. liver. If untreated.  In all abnormal locations. 3. which results in an abnormal implantation. a situation. rapid and sustained rise in blood pressure. in fatal cases. in severe cases the diastolic pressure is consistently above 100 mmHg.  The wall of the fallopian tube is thin and unless the ectopic pregnancy is discovered. widespread microinfarcts in brain. Seen particularly in association with multiple pregnancies. there may be a further complication – damage to the uterine arteries with arterial bleeding. the trophoblast readily penetrates the mucosa and wall. Ectopic Pregnancy Ectopic pregnancy refers to any gestation that develops outside the endometriun. and the host implantation site develops decidual changes and syncytio-trophoblasts. and fetus.  The direction of rupture varies: 1. shock. Eclampsia is now a fare complication of pregnancy. leiomyomas.  The appearance of ectopic pregnancy resembles that of placenta increta and percreta of the uterus. with the blood pressure under 100 mmHg diastolic and no proteinuria. leading. Most cases are mild. Patients develop severe systemic disturbance. Rupture into the broad ligament lead to extraperitoneal hematoma. anuria and fits. with widespread occlusion of blood vessels.  Tubal rupture with subsequent hemorrhage is a life-threatening complication.  Abdominal pain is the most common symptom. the fertilized ovum undergoes its usual development with the formation of placental tissue. endometriosis. fibrinoid necrosis of vessel wails.  Etiology of tubal pregnancy: salpingitis. If the implatation is interstitial. Usually development is limited and the fetus dies. In the kidney. to proteinuria. this may lead to fetal hypoxia in late pregnancy. particularly during labour. kidney and other organs. leading to partial blockage of the tube. Rupture directly into the peritoneal cavity. . The fetus may also suffer intrauterine growth retardation and have low birth weight.  Gestational Trophoblastic Disease The clinical term “gestational trophoblastic disease” include of hydatidiform mole (complete and partial mole). Placental ischemia takes place.

Partial moles have a lower malignant potential than complete moles. blood vessels.  In this condition there are four characteristic features. Most believe that it is due to disturbances of cyclical ovarian estrogen and progesterone levels. Complete type.  It is difficult to determine the relative frequency of complete and partial moles. lobules. and the mole is aborted shortly thereafter. The most important complication is the development of choriocarcinoma. unlike complete mole.  The invasive mole. and the form. accompanied by altered responsiveness of breast tissues in women approaching the menopause. ductules and stroma. i. if any.  In partial hydatidiform mole. uterine perforation.  Microscopically. show varying degrees of trophoblastic proliferation.  There is no embryo. trophoblastic proliferation is usually prominent. This is mainly an increase in the amount of collagen rather a true growth of fibrous tissue. Partial type.  2. which resemble a bunch of grapes. Fibrosis. . Benign diseases of the breast Fibrocystic disease   Fibrocystic disease is the most common disorder of the female breast. Blood vessels are typically found within the chorionic villi and contain fetal (nucleated) red blood cells. Invasive type. since the entity of partial mole has only recently been recognized. there is frequently an associated embryo. also called chorioadenoma destruens. trophoblastic embolism. being composed of seemingly normal small villi along with villi that have accumulated considerable fluid. and mitotic activity can be marked but there is no danger of malignancy. The cause of fibrocystic disease is uncertain. which duplicate to 46XX.  Complete mole results from fertilization of an egg in which the maternal chromosomal material has been lost or inactivated by a single sperm with a 23X set of chromosomes. which may simulate carcinoma. with the maternal chromosomes remaining. The villous outlines commonly have a scalloped appearance. grossly swollen chorionic villi. is a hydatidiform mole that has invaded the underlying myometrium.  Theca lutein cysts (hyperreactio luteinalis) may occur with any form of trophoblastic disease and may be prominent with invasive moles.  The embryo dies at an early stage before the placental circulation has developed. coagulopathy.  Partial hydatidiform mole is generally the result of fertilization of an egg by two paternal sets of chromosomes.  There is proliferation of acini and stroma. This results in triploidy.  Sclerosing adenosis (fibroadenomatoid hyperplasia or fibroadenosis) is localised condition.  In complete hydatidiform mole.  In partial hydatidiform mole two populations of chorionic villi exist. partial hydatidiform mole resembles complete mole. invasive moles show less hydropic change than complete moles. and infection.  Microscopically.  Complications of complete hydatidiform mole include uterine hemorrhage. 2.  Trophoblastic proliferation is focal and usually less pronounced than in the complete mole. 3.  Uterine perforation from the locally infiltrative disease is the major complication.  Fibrocystic change is characterized by hyperplastic overgrowth of components of the mammary unit. which the disease takes varies according to the relative proportions of these features: 1. some of which show hydropic swelling. Adenosis.141 Hydatidiform Mole 1.e.  The fetus associated with a partial mole usually dies at approximately 10 weeks of gestation. and chorionic villi then contain few.  This is an increase in the number of lobules and in the size of existing lobules.

Fibroadenoma     Fibroadenoma is a bening nodular proliferation. rubbery replacement of breast tissue. c) Epithelium forms clefts: these are due to pressure from the projecting fibrous tissue. the prostate is enlarged. 3. hyperemia and foci of necrosis frequently accompany acute inflammatory involvement. The fibroadenoma is therefore best regarded as a form of hormone-dependent nodular hyperplasia. glistening. it is not safe to assume that a lesion is benign because it has a fluid-filled cyst. areas of fibrocystic changes appear as firm. Fibroadenoma presents as a mobile lump in the breast of young women. It occurs most commonly due to ascent of bacteria from the urethra. Prostatic .  Histologically: cysts are lined by flattened epithelium derived from the lobular-ductal unit and are filled with watery fluid. fibrosed and shrunken. the prostatic acini are dilated and filled with neutrophilic exudate. elastic consistency. Histologically: a) Small acinar and duct structures resembling normal brest. Microscopically. Chronic prostatitis   Macroscopically.  Macroscopically. macrophages and neutrophils within the prostatic substance. Histologically. well-circumscribed. appearing as firm. Macroscopically. The infection may occur spontaneously or may be a complication of urethral manipulation such as by catheterization. but may also result in the development of single breast lumps. b) Fibrous tissue arranged around acini. the prostate may be enlarged.  Epithelial hyperplasia is the most important component because it forms a link between simple proliferation and malignant change. As some carcinomas of the breast may be associated with cysts. 4.  They range in size from those detectable only by histology to palpable lesions I-2 cm in diameter. greish cut surface. Edema. rather than a true benign tumor. etc. such as: a) Proliferation of myoepithelial layer. Fibrocystic change. b) Proliferation of ductal epithelium forming an irregular network (atypical ductal hyperplasia). and occasionally by lymphogenous or hematogenous spread from a distant focus of infection. Acute prostatitis      Acute prostatitis is characterised by acute focal or diffuse suppurative inflammation of the prostate. Macroscopically. cystoscopy. less often by descent from the upper urinary tract or bladder. now considered to be a component of fibrocystic changes and not a true neoplasm.  There are many histological variations within fibrocystic disease. chronic and granulomatous types. rubbery. plasma cells. in which cysts may be visible.  Cysts are a prominent component. The lining epithelium may show apocrine metaplasia. Cut section shows multiple abscesses and foci of necrosis.142  This presents as palpable thickening and nodularity of breast tissue. fibroadenomas are typically 1-3 cm in diameter. swollen and dense. increasing in incidence with the approach of the menopause. c) Uniform proliferation of acinar epithelium without acinar expansion (atypical lobular hyperplasia). There may be diffuse acute inflammatory infiltrate. the diagnosis of chronic prostatitis is made by foci of lymphocytes.  Obstruction of ducts leads to dilatation on the ducts and acini. Cyst formation. Diseases of male genitalia Prostatitis may be acute.

. Morphology Macroscopically: The enlarged prostate is nodular.glandular.  Fibromuscular hyperplasia when present as dominant component appears as aggregates of spindle cells forming an appearance akin to fibromyoma of the uterus. puberty.   Complications     Chronic retention of urine. which enables the surgeon to enucleate the nodular masses. Estrogen excess (cirrhosis. probably caused by leakage of prostatic secretions into the tissue.  In primarily glandular benign nodular hyperplasia the tissue is yellow-pink. there is enlargement of the breast as a firm. In most cases it is idiopathic. chlorpromazine. rubbery mass beneath the nipple. prolactin excess (hypothalamic or pituitary disease). adrenal tumor. Microscopically. The appearance on cut section varies depending upon whether the hyperplasia is predominantly of the glandular or fibromuscular tissue. gonadotropin excess (testicular tumor). digitalis).  Glandular hyperplasia predominates in most cases and is identified by exaggerated intraacinar papillary infoldings with delicate fibrovascular cores. but may be a sign of underlying endocrine disturbance. smooth and firm. lymphocytes. raised. honeycombed. Gynecomastia of male breast      Gynecomastia of male breast is most commonly idiopathic. giving the clinical impression of psoriatic carcinoma on rectal examination. soft.  The hyperplastic nodule forms a mass mainly in the inner periurethral prostatic gland so that the surrounding prostatic tissue forms a false capsule. may be unilateral (70% of cases) or bilateral. Microscopically:  Hyperplasia of all tissue elements in varying proportions . homogeneous and does not exude milky fluid. Granulomatous prostatitis is a variety of chronic prostatitis.  In mainly fibromuscular benign nodular hyperplasia the cut surface is firm. plasma cells and some multinucleated giant cells. the gland is firm to hard. Bening prostatatic hyperplasia (Nodular hyperplasia) Nodular prostatic hyperplasia has been suggested by some as precursor for development of prostatic cancer. exogenous estrogens). which is termed gynecomastia. Macroscopically. Enlargement of the male breast. drug-related (spironolactone. Bladder stone. Hydronephrosis. or could be of autoimmune origin. The male breast is normally rudimentary and inactive. the inflammatory reaction consists of macrophages.143  calculi and foci of squamous metaplasia in the prostatic acini may accompany inflammatory changes. consisting of fibroadipose tissue containing atrophic mammary ducts. and milky fluid exudes. Macroscopically. Other causes include: Klinefelter’s syndrome. fibrous and muscular take place. Cystitis and pyelonephritis.

They may be represented by 1. adrenal cortex hyperplasia. Dysfunction. 2. Acromegaly and gigantism  Excess of STH stimulates all mesenchymal derivatives (bones. Hyperfunction. the administration of hormones (cortisole. Its clinical manifestations (so called Cushingoid) are the same as in the disease (obesity of the upper part of the body). but the other signs are not clearly marked. All diseases of the endocrine system are divided into 1) congenital. adrenal. Itsenko-Cushing disease. sexual. Parathyroid gland. 3. epiphysis) and neuronal (hypothalamus). it is called gigantism. Osteoporosis.144 ENDOCRINE PATHOLOGY       The endocrine system consists of a highly integrated and widely distributed group of organs whose primary function is the control of homeostases. Sexual glands. 1. In this case. 5.  Itsenko-Cushing disease occurs in adenomas from basophilic cells of anterior lobe of the pituitary or adenocarcinoma in rare cases. feet and hands enlarge). 2.  It results in obesity of face and body. cerebro-hypophyseal cachexia. nose. tuberculosis. Pituitary body.  The causes of these states are adrenals damage (tumor of zona fasciculata). and tumor. parathyroid) are closely connected with each other as well as with the central endocrine glands (pituitary. The most frequent are endocrinopathy of 1. The most frequent diseases of pituitary body associated with hyperfunction are Itsenko-Cushing disease. sexual glands atrophy occur). 1. Simmonds’ disease (cerebro-hypophyseal cachexia) is caused by necrosis of pituitary anterior lobe. Pancreas. diabetes mellitus. and gigantism.secreting pituitary adenoma. Pituitary dwarfism (nanism) develops in congenital hypoplasia of the pituitary body or its necrosis in children. acromegaly. 6. inner organ . Diseases of pituitary body Diseases of pituitary body may occur the symptoms of hyperpituitarism or hypopituitarism. Increased ACTH production causes cortex hyperplasia as well as increased production of glucocorticoids.  If the disease occurs in prepubertal boys and gerls. Hypopituitarism is characterised by less secretion of one or more of the pituitary hormones due to destraction of the anterior lobe (by metastases. Hyperpituitarism is characterised by oversecretion of one or more of the pituitary hormones due to the development of a hormone. elevation of arterial pressure. It manifests by cachexia. dysplasia. atrophy of insulin apparatus of pancreas. lower jaw. pancreas. It may occur after childbirth due to vascular embolism as well as due to syphilis. The term “acromegaly” means increased growth of extremities. hydrocortisone). 2.  The other glands also involve by the process (goiter.  If the disease occurs in adults.  The disease should be differentiated from Itsenko-Cushing syndrome. ischemic necrosis) and the development of a nonsecretory adenoma or others tumors. 2. A practical classification of endocrine pathology is based on the damage of the main (primary) gland. sclerosis and tumors may develop. 3. All peripheral endocrine glands (thyroid. thymus and epiphysis hyperplasia. connective tissue). and diabetes insipidus. 2) acquired. nephrolithiasis and chronic pyelonephritis may also develop. General underdevelopment of the organism with preserved proportions is observed. it is called acromegaly (the bones does not grow but ears. and sexual gland dysfunction. Thyroid gland. The most frequent diseases of pituitary body associated with hypofunction are hypophyseal nanism. 4. dystrophy. atrophy. Hypofuniction. cartilages. prednisolone. Adrenal glands.

sclerosis. Diseases of theThyroid gland Two significant functional disorders characterised by distinct clinical syndromes are discribed. Hyperthyroidism Hyperthyroidism (thyrotoxicosis) is a hypermetabolic clinical and biochemical state by excess production of thyroid hormones. Cachexia (suprarenal cachexia) Cardiovascular insufficiency. but three most common causes are: 1. Hyperplasia of thymus and lymphatic peripheral tissue.g. Diseases of adrenal glands     Adrenal glands consist of cortex and medullar substance. congenital hyperthyroidism Goitre Goitre is defined as thyroid enlargement caused by compensatory hyperplasia and hypertrophy of the follicular epithelium is response to thyroid hormone deficiency. necrosis due to vascular thrombosis. Diabetes insipidus is caused by tumors. Morphology       Hyperpigmentation of the skin and mucous membrane due to excessive production of melanin stimulating hormone. metastatic tomors of thyroid. The cause of death:    Acute adrenal failure. Secondary Addison‟s disease is caused by metastases in the adrenal glands. Goitre is classified according to their morphology and epidemiology. 3. 2. aldosterone. damage of the pituitary body (decreases ACTH or corticotropin releasing factor). There are: hyperthyroidism (thyrotoxicosis) and hypothyroidism (mixedema). hemorrhage. One of them causes primary Addison‟s disease (genetic autoimmune disturbances). Toxic multinodular goitre. Simple goitre (diffuse nontoxic or colloid goitre).145 atrophy. which develops in bilateral lesion of adrenal cortex with the development of acorticism (absence of hormones) or hypoadrenocorticosis. course. Myocardial atrophy. It manifests itself by increased urine excretion due to deficiency of Antidiuretic hormone. amyloidosis. In 1849 Addison described the so-called bronze disease. Gastric mucosa atrophy. and trauma of the posterior lobe of pituitary. tuberculosis. Toxic adenoma. Diffuse nodular (mixed). According to the morphology goitre may be: 1. Changes of the lumen in the aorta and large vessels. zona fasciculata which produces glucocorticoids. 2. Graves‟ disease (diffuse toxic goitre). 2. I. Less frequent causes are thyroiditis. The causes of Addison’s disease are divided into two groups: 1. According to the histology there are 2 types of goitre: . inflammation. struma ovarii. II. Hyperplasia of the cells of islets of Langerhans in the pancreas (hypoglycemia). 3. Many diseases may cause hyperthyroidism. Nodular goitre (multinodular goitre or adenomatous goitre). The most frequent disease associated with hypoadrenalism is Addison’s disease. and sexual dysfunction. reticular zone which produces sexual hormones. functional and clinical peculiarities. There are 3 zones in the cortex: glomerular zone which produces mineralocorticoids e. 3.

particularly heart failure and a predisposition to hyperlipidemia and hypothermic coma. II. increasing lethargy and sensitivity to cold. The causes of death are cardiac insufficiency and cachexia.146 1. hoarseness and deepening of voice. This produces sporadic cretinism and is due to failure of normal T3 and T4 synthesis. Cretinism or congenital hyperthyroidism.  Hashimoto’s thyroiditis. This is now rare. or aggressive subtotal thyroidectomy for hypothyroid Graves’ disease. Morphology: prismatic epithelium turns into cylindrical. endemic cretinism may develop (physical and mental retardation). etc. epithelium proliferation with formation of papillae. formation of lymphoid follicles with germ centers are observed. Exophthalmus takes place. Hypothyroidism (mixedema) Hypothyroidism is a hypometabolic clinical state resulting from inadequate production of thyroid hormones of prolonged periods of. Endemic goitre develops in the areas with iodine deficiency in the drinking water (the Urals. and various internal abnormalities. Myxedema It is the adult hypothyroidism. hypertrophy of the left ventricle of the heart. exophthalmic goitre) Diffuse toxic goiter is an autoimmune disease. Sporadic goitre manifests in young and old age. The outcome is diffuse interstitial sclerosis. Colloid goitre may be macrofollicular and microfollicular as well as mixed type. The clinival manifestations of hyperthyroidism are divided to into group: I. In the majority of cases the disease is diffuse.  Inherited enzyme defect. This may be colloid. coarse dry skin. Middle Asia. trachea. Thymus enlargement causes lymphoid tissue hyperplasia and adrenal hypertrophy. diffuse or mixed. Endemic. larynx. colloid vacuolization. In the liver. a protuberant abdomen.g. from resistance of the periferal tissues tj the effects of thyroid hormones. which occurs a puffy face and enlarged tongue (coarse features). there is serous edema causing thyrotoxic liver fibrosis. which is due to reduced metabolic rate. or rarely. which is usually as a result of total thyroidectomy for malignant disease. III. primary hyperplasia. This goitre may be the cause of Basedow‟s disease. Parenchymal. . In case of epithelial proliferation the disease is termed proliferating colloid goitre. In the other organs. Basedow’s disease. The functional activity is decreased. serous edema and lymphacytic infiltration myocardial interstitial spaces develop (thyrotoxic heart). It produces the clinical syndrome. The thyroid gland has the structure of colloid or parenchymal goitre. The main causes of myxedema are:  Surgical ablation of the thyroid gland. 2. According to the epidemiology goiter is classified into: 1. There is progressive slowing of physical and mental activity. Parenchymal goitre is characterized by epithelium proliferation with formation of small follicle-like structures without colloid. It consists of follicles.  Some drug e. Colloid. Graves’ disease      Graves’ disease (or diffuse toxic goiter. with disturbance of their function. puffy face. The main causes of cretinism are:  Untreated maternal hypothyroidism. Siberia. thinning of hair (particularly of the eyebrows). lymphoid plasmocytic infiltration of the stroma. It does not influence the organism as a whole. 2. due to better prevention. The term “myxedema” connotes non-pitting edema due to accumulation of hydrophilic micopolysaccharides in the ground substence of dermis and others tissues. lithium. Sporadic. recognition and treatment of maternal hypothyroidism but it is still a problem in some areas of the world where endemic goiter due to dietary iodine deficiency is seen. Switzerland). which is usually nodular. In children. but it can cause compression of the esophagus. and delayed physical and mental developmental milestones.

Macroscopically. These cells have abundant oxyphilic or eosinophilic and granular cytoplasm due to large number of mitochondria and may cantain large nuclei. 4. at administration of some “drugs”. plasma cells. Morphology     Two varieties of Hashimoto’s thyroiditis are seen: classic from (more common). The etiology is inknown.dependent). locally scattered lymphocytic infiltration and invasion of the adjusent muscle by the process. Hashimoto’s thyroiditis    Hashimoto’s thyroiditis is a destructive autoimmune thyroiditis leading to hypothyroidism. firm and rubbery enlargement of the thyroid which may weigh 100-300 gm. atrophy of thyroid tissue.  The follicular epithelial cells are transformed into their degenerated state termed Hurthle cells (Askanazy cells). the thyroid gland is contracted. and complicated genetic syndromes. Diabetes mellitus Diabetes mellitus is a chronic clinical syndrome characterised by hyperglycemia due to deficiency or defective response to insulin. which are generally atrophic and are often devoid of colloid. Hashimoto thyroids proceed to primary atrophic thyroiditis or lead to carcinoma. Sectioned surface is fleshly with accentuation of normal lobulations but with retained normal shape. Microscopically: extensive fibrocollagenous replacement.147 Thyroiditis Thyroiditis is classified into the following types: 1. Secondary diabetes may occur in pancreatic diseases. Hashimoto‟s thyroiditis. the classic form is characterised by diffuse. Spontaneous diabetes mellitus is an independent disease and can be of 2 types:  Type I (insulin. Microscopically. This is classified into: 1. . It is most common in middle age. Infectious thyroiditis. Riedel‟s thyroiditis (or invasive fibrous thyroiditis. The following autoantibodies against different thyroid cell antigens are detectable in the sera of most patients: 1. stony-hard. symmetric. assemetric and adherent to the adjasent structures. 2. acromegaly. immunoblasts and macrophages. the classic form shows the following features:  There is extensive infiltration of the gland by lymphocytes. with formation of lymphoid follicles having germinal centres. Riedel’s thyroiditis     Riedel’s thyroiditis is characterised by stony-hard thyroid that is densenly adherent to the adjacent structures in the neck. Itsenko-Cushing disease.  There is decreased number of thyroid follicles.  There is slight fibrous thickening of the septa separating the thyroid lobules. 2. Thyroid microsomal thyroiditis.m Thyroglobulin autoantibodies.  Type 2 (insulin-independent). Granulomatous thyroiditis (de Quervain‟s thyroiditis or giant cell thyroiditis). Riedel‟ struma). 2. affecting women more often than men. Cut section is hard and devoid of lobulations. 3. Macroscopically. a good example of organ-specific autoimmune disease. and fibrosing variant (only 10% cases).

diabetic glomerulosclerosis. In the lungs. Diabetic macro. Complications:       Diabetic coma. Diabetic glomerulosclerosis may be diffuse and nodular as well as mixed type. liver. increased arterial pressure). Mesangium hyalinosis and glomerulosclerosis take place. Vasculitis takes place. hyalinosis. and sclerosis with lipohyalin. lymphatic glands: infiltration of brstiomacrophagal system and skin with cell lipids (xantomatosis) develop. diabetic glomerulonephritis and glomerulosclerosis develop. retina.148 3. In the spleen. viruses. The liver is enlarged. In the kidneys. which disturb beta-cell nutrition (bacteria. . lipogranulomas consisting of macrophages and gigantic cell of foreign bodies are present in the walls of the arteries. myocardial infarction.and microangiopathy is seen in the vessels. pancreas. Considerable amount of sugar is formed from the fats and proteins causing hyperlipidaemia. Risk factors of different kinds of spontaneous diabetes are different. brain. Accompanied with macroangiopathy: gangrene of extremities. autoimmune reactions). 4. gangrene. Pathogenesis Insulin insufficiency increases blood glucose amount because cellular membranes are closed for glucose . The death is caused by coma. digestive tract mucosa. Diabetes of pregnant occurs during pregnancy. skeletal muscles. Microscopically proliferation of mesangial cells in response to mesangium clogging with “ballast” metabolic products and immune complexes are observed. Latent (subclinical) diabetes is not evident. and nerves. Diabetic retinopathy is a leading cause of blidness. some of them are hypertrophic.and ketonemia. fat degeneration is observed. There is generalized microangiopathy in the kidneys. Microangiopathy is characterized by plasmatic saturation. Degeneration and hyalinosis are observed in the islets.hyperglycemia and glucosuria develop. Etiopathogenetic factors:    Genetically determined disturbances of the number and structure of beta-cells. Morphology              The pancreas is diminished with lipomatosis and sclerosis. glycogen is absent. Diabetic nephropathy (acute and chronic renal failure). Macroangiopathy is arterial atherosclerosis. aceton. Its clinical manifestations are Kimmelstiel-Wilson syndrome (proteinuria. increase of activity of adrenergetic nervous system. Environmental factors. Infectious sepsis. edema.

b) Embryogenesis from Day 16 to the end of the 3rd month (75th day).  The normal and pathologic development and growth can be divided into the following stages: 1.  Short broad hands with a single simian crease on the palm. Trisomy 21 type – 47XXC2 or 47XXYC1. Gross appearance:  Short stature.  Hyperflexibility of joints and lack of Maro reflex. It stage occurs before the fertilization of the ovum. b) These arising in single gene mutations.  Duration of the prenatal period is 40 weeks (280 days) or 10 lunar months or 9 calendar’s months. Development after fertilization is called kymatogenesis. the case is called mortinatality.  Fetal pathology. is called prenatal pathology. It is a disorder associated with autosomes.  Low-bridged nose. Pathology of embryogenesis is called embryopathy. Gametopathy      Gametopathy is an injury of formation and maturation of the gametes during ovo. Chromosome mutations are called chromosomal aberrations. Currently more than 80% survive to age 30 or beyond. Genetic injuries in origin can be deviled into three groups: a) Those associated with karyotypic aberrations.149 PRENATAL PATHOLOGY  The period of fetus development beginning with the moment of fertilization to the birth of the child is called Prenatal period. The majority of cases of Down’s syndrome are due to nondisjunction of maternal meiosis. The most frequent is trisomy 21 (Down syndrome) and trisomy 13 (Patau’s syndrome).  Short crooked fifth finger. Down’s syndrome        Down syndrome is the most common of the chromosomal disorders and a major cause of mental retardation. which occurs in this period.formation and maturation of the gametes. Progenesis is characterised by gametogenesis. Pathology of gametogenesis is called gametopathy.e. c) Those suspected of resulting from multifactorial inheritance. Pathology of fetogenesis is called fetopathy. At present about 150 autosomal recessive genetic defects and 200 defects with autosomal dominant inheritance are known. The risk of the development of Down syndrome increases with maternal age. Turner’s syndrome. This intrauterine phase can be divided into: a) Blastogenesis from Day 1 to Day 15 of gestation. Pathology of blastogenesis is called blastopathy.  Muscle hypotonia. trisomy 18 (Edward’s syndrome). i.  The case of fetal death before the 14th week of gestation is called abortion that within the period of 14-22 weeks is called late abortion. Virtually all the chromosomal syndromes are characterized by congenital anomalies. Klinefelter’s syndrome.and spermatogenesis until fertilization. a term that implies the interaction of two or more genes of small effect with environmental factors. c) Fetogenesis from the 4rd month of gestation to delivery (from 76th to 280th day).  Flat facial profile. 2. The most causes of death are interrcurrent infections or cardiac insufficiency. Gametopathy occurs in gene mutations and chromosomal aberrations. . If the fetus dies on the 22nd week or later (until the delivery or during it). There are also defects connected with sex X chromosome.

 Short sternum and small pelvis.  Cardiac defects: patent. rocker-bottom feet. double uterus and vagina.  May be leukemia. Survivors have severe mental retardation and failure to thrive. ectopia of spleen into pancreas.  Micrognathia and low-set ears. May die in the neonatal period.  Thyroid dysfunction: hyperthyroidism. Patau’s syndrome    Trisomy 13D – 47XXD or 47XYD occurs at frequency of 1 in 20000 births.  Absence of the corpus callosum and incomplete development of the cerebellum.  Prominent occiput.  Rocker-bottom feet.  Polydactyly.  Microphtalmos.  The mouth is often open and protruding tongue. Somatic anomalies:  Short stature. Characteristics:  Microphaly and archinencephaly.  Neck and lower back.  Scalp defect. particularly of the lungs. a form of senile dementia.  Brushfield spots (the iris may be speckled). . and the majority do not survive beyong 1 year.  Epicanthic folds.  Virtually all patients with trisomy 21 older than 40 years of age develop neutropathologic changes characteristic of Alzheimer disease.  Cardiac dextraposition and interventricular septal defect.  Flexion of fingers (index over third).  Apneic spells and myoclinic seizures.150   Dysplastic ears. Edward’s syndrome     Trisomy 18E – 47XXE or 47XYE.  Hair lip. Turner’s syndrome   It is gonadal dysgenesis (defective second X chromosome – 45 X0). and those who survive have severe mental retardation.  Coloboma of the iris. ductus arteriosus and interventricular septal defects.  Cleft palate.  Extensive visceral defects: polycystic of kidneys.  Abnormalities of the hips and feet (syndactyly).  Patients with Down syndrome have abnormal immune responses that predispose them to serious infections.  Low intelligence.  Anophtalmos.  Oblique palpebral fissures.  Gastrointestinal anomalies.  Congenital heart defects.  Meckel‟s diverticulum.  Renal malformations. Most children die in the first month. Clinical significances:  Mental retardation is usually severe.  Hemangiomas of the head.  Reduced interpupillary distance. and hypothyroidism. goiter. Characteristics:  Hypertonicity.

This type of malformation includes the dicephalus (to spinal columns but only one pelvis). Holocardius Acephalus is the most frequent of the free double malformations in which only the trunk and lower extremities are clearly identifiable. Conjoined double malformations occur: 1. The important feature is the reduplication of the body axis (head.  Low-set ears..  Manifestations of blastopathies are different: a) Superficial or deep implantation of blastocyst (causes defects of development. diprosopus (reduplication of the face). The most frequent cause of blastopathy is chromosomal aberration in combination with harmful effect of environmental factors.  Ovaries are replaced by white “streaks” of fibrous stroma devoid of follicles. Free double malformations are designated as twins (gemini).  Double malformations may be free and conjoined: I. b) Complete symmetrical double malformations show a partial fusion between two generally mature fetuses. Asymmetrical double monsters have one well developed and one rudimentary or hypoplastic twin. i. there is only an incomplete reduplication of the body axis.  Peripheral lymphedema at birth. Characteristic laboratory and morphologic findings are:  Negative sex chromatin test.  Secondary sex characteristics are absent. b) Disturbance of embryo orientation (umbilical-cord defects are the most frequent). Clinical significans:  It is an important cause of sterility in the female.  Webbing of the digits or of the axillae. Symmetric forms or diplopagus represent two equally well developed embrional primordial that are connected to each other by a partial fusion of tissues.151    Primary amenorrhea. especially those in the sacrococcygeal area. c) Empty embryo sacs (blastocytes without an embryo).  Increased gonadotropin. and ischiopagus (“Siamese twins”). Some of the congenital teratomas. they may be connecting only by the placenta or the umbilical cord. or they may be malformed. The rudimentary twin is always abnormal. shape. II.  Uterus. Asymmetric (parasitic) or heteropagus (one of the twins is underdeveloped). localization of placenta).  Reduced levels of ovarian estrogenes. They may be independent of each other.  Low posterior hairline. 2.  Pigmented nevi. They may be: a) Incomplete individuals result from extensive fusion i.e. and is either externally attached to or internally included in the body of the better-developed sibling (fetus in fetu). are actually asymmetrical monsters. Teratomas are regarded as asymmetric monsters.  Shield – like chest with widely spaced nipples. They may be identical and fully developed (monosigotes twins).  Coarctation of the aorta.  Cubitus valgus (an increase in carrying angle of the arm). It is called cephalopagus.  Normal intelligence. Embryopathy . ovarium and fallopian tubes are infantile. while the head is absent.  Webbing of the neck.e.  High-arched palate. craniopagus. trunk. thoracopagus. Blastopathy   Blastopathies occur during the first 15 days from the moment of fertilization. or spinal column). d) Double malformations are reduplicated embrional primordial that are either primary or the result of later devision.  Senile facies. or they may be in direct bodily contact. Usually they cannot live.

 Division failures are defects caused by incomplete cleavage. Many hollow organs originate as strands and cords of cells. congenital cardiac anomalies.  Congenital malformations are morphologic defects that are present at birth. myocarditis. Causes of the congenital malformations I.  Dysplasia is a defect caused by abnormal organization of cells into tissues. hepatosplenomegaly. may induce malformations in the fetus and infant. According to the character of involvement. which was not fully established in embryogenesis. This period is called teratogenic termination period. drugs.  Aplasia is absence of the organ coupled with persistence of the organ anlage or a rudiment that never developed completely. If these cells do not die in a predetermined manner. when that process depends on the involution and programmed death of cells. anticonvulsants. warrafin (oral anticoagulant). 2. The term congenital does not imply or exclude a genetic basis for malformations.  Isolated (one organ). thus forming a central cavity or lumen. Genetic factors.  Radiation. Any congenital defect may manifest as one of the following changes:  Agenesis is the complete absence of an organ pri-mordium.  Alimentary tract. rubella (R).  Ectopia or heterotopia is an anomaly in which an organ is outside its normal anatomical site. to which the mother was exposed during pregnancy. cataracts. pneumonitis. Heterotopic parathyroid glands can be located within the thymus in the anterior mediastinum.  Central nervous system. Thus. herpes virus (H).  Pathologic development is connected with the termination period in which the causative agent acts.152  Embryopathy is a pathology developed within the period of 16 . and bone defects. The latter include fever. chorioretinitis.  Urinary system. Classification of congenital defects 1. and vesicular/hemorrhagic skin lesions. androgenic hormones. The list includes thalidomide.  Systemic (several organs of one system). the fingers will be conjoined or incompletely separated (“syndactyly”). Each organ has its own period of teratogenic factor action. Environmental influences. such as viral infections. . folate antagonists.  Hypoplasia refers to reduce size due to the incomplete development of the organ. II.  TORCH infections are caused by Toxoplasma (T).75 days and occurs by the development of the congenital malformations. and irradiation.  A variety of drugs and chemicals have been suspected to be teratogenic. Atresia of the esophagus is characterized by partial occlusion of the lumen. ectopic heart is located outside the thorax.  Multiple (in different organs and systems). Fingers and toes are formed at the distal end of the limb bud through programmed death of cells between the primordia that contain the cartilage. and a number of other (O) bacterial and viral agents. alcohol. although they may not become clinically apparent until later in life. etc. the centers of which are programmed to die. According to localization. defined as a malformation having either cosmetic or functional significance.  Involution failures are defects due to the persistence of embryonic or fetal structures that should involute at certain stages of development. including growth and mental retardation. Spina bifida is an anomaly in which the spinal canal has not closed completely and the overlaying bone and skin have not fused. encephalitis. hemolytic anemia. cytomegalovirus (C). occurring early in gestation may also cause chronic sequelae in the child.  Cardiovascular system. Such infections. a situation that results in abnormal histogenesis.  Atresia refers to defects caused by incomplete formation of a lumen. It is estimated that about 3% of newborns have a major malformation.  Dysraphic anomalies are defects caused by failure to fuse. thus leaving a midline defect.

during the first 3 months of gestation. the cauda equna or the area medullovasculosa (see above). Craniorachischisis totalis due to failure closure of the neural tube the convexity of the skull is absent and the spine is represented only by it‟s bodies with no posterior covering. Agenesis of the corpus callosum is a component of arrhinencephaly. Hydrocephalus is meant an increased amount of cerebrospinal fluid in the ventriculosubarachnoid pathways of the brain. the medulla and the foramen magnum. 3. and cardiovascular system are most frequently involved because these systems have the longest teratogenic terminal period. Pachygyria is the appearance of large gyri in the cortex due to inadequate differentiation of sulci. remain silent until middle age. The most important malformations are: I. like bicuspid aortic valve. Spina bifida occulta due to the failure of closure of the sacral bones (rachischisis): a) Meningocele. a combination of meningocele and hydromyelia (ballooning of the spinal cord due to a hydrophic accumulation of the fluid in the central canal). 6. Congenital stenosis of the aqueduct. with an added sharp curvature of the neuraxix at the cervicomedullary junction).  Congenital heart defects are the most common forms of heart disease in children. 2. Amyelia. Errors of migration (Heterotopies. 10. II. 12.153 Central nervous system. like a small ventrical septal defects (VSD) or patent foramen ovale may never cause any difficulty at all. 13.  Most defects manifest themselves within the first year of life. 11. Status verrucosus is a wart-like appearance of the cortex produced by a disorderly arrangement of the neuroblasts so that fissuration and sulcation are irregular and unpredictable. 2. which protrudes because of the accumulation of fluid. They occur in about 1% of neonates and in 18% of spontaneous aborted and stillborn fetuses. 4. Microgyria (secondary fissures are lacking). Arnold-Chiari malformation is a group of different combinations (the full deformity is a herniation of the posterior cerebellum. Microcephaly is decrease of the brain‟s size. or total aplasia of the spinal cord. 5. Cyclopia (one eye in the middle of a deformed forehead). c) Meningomyelycystacele or syrengomyelocele. 9. Ectopias) 1. Diplomyelia (Each half of the spinal cord develops separately over many segments). Diastematomyelia (each half has only one dorsal and one ventral horn with a intervening cystic cavity to represent the central canal). such as large ventricular septal defects and tetralogy of Fallot. 3. Errors of fusion 1. Anencephally is an absence of the cranial vault (acrania) and of the brain (anencephaly) and a short neck. diverticulum – like bulging of an arachoid sac filled with clear spinal fluid.  Others. b) Meningomyelocele in which the arachnoidal sac also contains parts of the spinal cord. from the 18th day to the 50th day.  Still other defects. Malformations of the nervous system I. 8. Arrhinencephaly (the olfactory buld and tracts are absent in the mildest form of the disorder). Congenital malformations of the heart  Congenital malformations of the heart represent structural changes that originate during the development of the septa and the rotation of the arterial heart. 7. when degenerative changes of the abnormal valve cause stenosis. Septal defects .

3) Ventricular septal defect (Roger‟s disease). Ventricular septal defect. III. Aorta overriding the right ventricle (aorta dexraposition). III. Stenosis or atresia of the pulmonary outflow tract.  Aortic coarctation.  Congenital mitral insufficiency. Stenoses  Tricuspid stenosis or atresia.  Dextraposition of the heart. No shunt 1) Coarctation of the aorta. II. 3) Transposition of great vessels. Tetralogy of Fallot consists of 1. Defect of interatrial septum. Classification anomalous development of the heart (by Ebbott) I. B. 2) Aortic stenosis.  Anomalies of the pulmonary veins include openings into the superior or inferior vena cava or the coronary sinus. 2. Transposition defects  Dextraposition of the aorta (Eisenmenger’s syndrome.  Mitral stenosis or atresia. Stenosis or atresia of the pulmonary outflow tract. Ventricular septal defect. 4. Pentalogy of Fallot consists of 1. C. Stenosis or atresia of the pulmonary outflow tract. 4. II. VI. 3. Combined heart defects A. Right ventricular hypertrophy. 5. Acyanotic shunt (left-right) 1) Patent ductus arteriosus. 2) Eisenmenger‟s complex (variant of the tetralogy of Fallot). 3. Ventricular septal defects (Roger’s disease). 2) Atrial septal defect. 2.  Aortic stenosis or atresia.  Pulmonary stenosis. Right ventricular hypertrophy. IV. Aorta dexraposition. V. Complete absence of the ventricular septum. . tetralogy Fallot). Hypertrophy of the right heart. Valvular insufficiency  Congenital tricuspid insufficiency (or Ebstein’s anomaly). Examplies of some heart defects Patent ductus arteriosus (PDA)  Before birth the ductus arteriosus (DA) is the only route by which blood in the right ventricle (RV) can reach the systemic circulation. 2. Cyanotic shunt (Right-left) 1) Tetralogy of Fallot. Persistent fetal vessels  Patent ductus arteriosus (with many congenital cardiac defects).154    Patent foramen oval (Atrial septal defect). with or without septal defect (cor bilocular or cor triboculare). 3. Trialogy of Fallot consists of 1. Ventricular septal defect.

When this occurs. With a sizable atrial defect. Within a day or two. Dilation of the atria. they allow significant left-to-right shunting. tip) of the heart. Left ventricular output is usually near normal so that these infants develop normally. Deficient formation of septum secundum. the DA fails to close. pressures in the two atria are similar and the right ventricle fills more easily than the left. But. After birth. Over the course of several decades.e. blood is shunted right-to-left and cyanosis may ensue. which occurs following lung inflation after birth. shunts are reversed and cyanosis appears or becomes more prominent. After birth. The ventricles are separated by the growth of the muscular septum and by the growth and fusion of the endocardial cushions near the atria. Before birth. the pulmonary arterial muscle will atrophy and a normal circulatory pattern will be established.. VSD’s may be of little consequence if they are small. If pulmonary resistance exceeds systemic resistance (due to hypoplastic lungs. In atrial septal defects. 3. Deficient formation of septum primum. With the drop in pulmonary arterial pressure. the pulmonary artery pressure falls to normal or near normal levels soon after birth. This progressively narrowed bed offers greater and greater resistance to pulmonary blood flow. since now (after birth) the pulmonary (right) pressure is lower than the systemic (left) pressure.e. for instance). the resulting atrophy of the right ventricle makes this chamber more distensible than the left ventricle. If the septal defect is operatively closed at this stage. such patients will develop right-sided cardiac failure since the right ventricle is incapable of forcing all of the caval blood through the restricted pulmonary vascular bed. An ASD II may form in any of four ways: 1.155     The DA is located superior to the bifurcation of the pulmonary arteries and enters the aorta just distal to the left subclavian artery. Atrial septal defects (ASD)              The most common ASD is a secundum ASD or ASD II. A secundum ASD means that the ASD is reminiscent of the ostium secundum i. diastolic overloading of the right ventricle continues and both the right ventricle and atrium dilate and hypertrophy. the DA is usually functionally closed. The RV responds to increased flow and pressure with either dilatation (congestive heart failure) or hypertrophy. Consequently. if they are large. the blood shunts from left to right atrium. most of the blood enters the systemic circulation. thereby pulling septum primum and septum secundum apart. the ostium secundum is not covered over. 2. Combination of both. This shunt may be large if the septal defect is large. Resistance in the pulmonary arterial bed may eventually equal or exceed that in the systemic bed. If a large defect is not closed in time. It is invested with spirals of smooth muscle. 4. However. Not infrequently and often in premature infants. blood shunts from the aorta across the PDA and into the main pulmonary artery. not only does the vena caval blood enter the right ventricle but also much of the pulmonary venous blood from the left atrium enters the right ventricle as well. hence a PDA. VSD’s are of little consequence since the pulmonary arterial pressure is equal to the systemic pressure and thus. which contract at birth in response to high tension (coming from the newly aerated lungs). . Pulmonary blood flow is greatly increased while oxyhemoglobin saturation in the systemic arterial system is normal. If the normal cardiac anatomy is now restored through surgery. Ventricular septal defects (VSD)    These are the most common of the cardiac defects. pulmonary vascular obstruction takes place within the pulmonary arterial bed. VSD’s can be located near the atrioventricular valves or nearer to the apex (i. The pulmonary arterial bed responds to this “over circulation” with smooth muscle hyperplasia and hypertrophy.

pneumonia and congestive heart failure. After a long time. i. In the latter situation. pulmonary blood flow may be greatly increased. Much mixing of blood occurs. the pulmonary and systemic circulations are disconnected. If the communication between the two circulations is adequate for oxygenation. He used the term la maladie bleu. This defect is commonly associated with Down’s syndrome (Trisomy 21). as is the RV. After birth. In this defect the aorta arises from the right ventricle and the pulmonary artery arises from the left ventricle. then the LV and then out the pulmonary arteries back to the lungs. Actually. Venous blood enters the RA. Common atrioventricular canal (CAVC)     In this cardiac malformation. it is usually inadequate and these neonates have marked cyanosis. Stenosis or atresia of the pulmonary outflow tract. undivided atrioventrical (AV) canal above the incompletely divided RV and left ventricle (LV). Aorta overriding the right ventricle.e. 2. blood from the right atrium (RA) and the left atrium (LA) enters into a common.156     Thus. With this leftward shift. Because of this left-to-right shunting. a VSD or a patent ductus arteriosus. Pulmonary venous blood enters the LA. Fallot did not actually coin the term. Ventricular septal defect. Whatever mixing of the two systems there is. The RV may also hypertrophy. Survival is dependent on any kind of mixing of oxygenated and unoxygenated blood whether through an ASD. What comprises tetralogy of Fallot? 1. This opens up a “hole” in the interventricular septum (hence a VSD). Right ventricular hypertrophy. . Thus. since venous blood (from the placenta) is oxygenated. resulting in cyanosis. These changes reflect the presence of pulmonary hypertension. Combined heart defects: Tetralogy of Fallot       It was Etienne-Louis Arthur Fallot in 1888 who well described this form of cyanotic heart disease. This underdevelopment of the conus results in malaligament of a band of muscle (the parietal band) that lies beneath the pulmonic valve. however. “tetralogy of Fallot”. then problems of cardiac failure and pulmonary hypertension will inevitably develop.. Transposition of the great arteries (TGA)         This is a fairly common defect and it is important to recognize it early since surgical correction is possible and successful. the basic abnormality is underdevelopment of the subpulmonary cone of muscle (conus). The pulmonary vessels become thicker by undergoing smooth muscle hyperplasia/hypertrophy. this band of muscle shifts anteriorly. Because the atrioventricular valves (mitral and tricuspid) are also formed by the endocardial cushions. edema. the blue disease. 3. blood shunts from right-to-left. resulting in stenosis/atresia of the pulmonary outflow tract. It was Maude E. In tetralogy. Abbott who first used this term tetralogy of Fallot in 1924. hemorrhage. then the RV and then out the aorta. the endocardial cushions fail to separate the atrioventricular canal into right and left sides. they are malformed as well. superiorly and to the left. the aorta is “looking down into” the RV (hence an “overriding” aorta). In utero. this defect causes no trouble. pulmonary pressure may equal or even exceed systemic resistance. the pulmonary vascular bed is faced with abnormally high pressures. leading to pulmonary congestion. It is thought to be due to abnormal development of the conal muscle beneath the two semilunar valves. 4. which obstructs the pulmonary outflow tract.

Double uterus with double cervix. The VSD also contributes to right ventricular hypertrophy. Meckel’s Diverticulum. . Congenital anomalies in the face (8th to 10th week of the embryonal period) 1. Congenital Cystic liver disease. with the narrowed pulmonary outflow tract. ganglioncells are absent in the region of the anorectal junction. Lateral facial clefts: a) Cheiloschisis or cleft lip (limited to the upper lip). Despite the nearly unbelievable variety of cardiac malformations that are possible. Accessory (Additional) kidneys. Reduplication of the urachus. Fallot’s congenital anomaly could be called “monology of Fallot” with the single underlying abnormality being an underdeveloped conus resulting in a stenotic or atretic pulmonary outflow tract. there is obstruction (hence right ventricular hypertrophy). b) Gnathoschisis (extend to the maxilla). Agenesis. the net result of these abnormalities can be reduced to a mercifully short list of clinical signs and symptoms. Stenosis. The right ventricle hypertrophies.   Septate uterus. The result is intestinal obstruction in affected neonates. Horseshoe kidney. hypoplasia. complete repair usually being done within the first two years of life. Congenital anomalies of the genital system I. Displacement. Female Congenital anomalies of the gastrointestinal tract             Agenesis (esophagus. right to-left shunt occurs across the VSD and the patient suffers from severe cyanosis. Polycystic kidney disease. II. Surgical repair is now highly effective. In all patients. This obstruction can be at the level of the pulmonic valve or in the right ventricle just beneath the pulmonic valve. Megaesophagus. intestinum). Fistulous tract of the esophagus with the trachea or main stem bronchi. Diaphragmatic Hernias. total reduplication of the qallbladder. Megacolon (dilation of bowel) in Hirschprung’s disease. in response to the increased resistance and because of the large VSD. Cryptorchidism. Pyloric stenosis. hyperplasia. Hypoplasia. in essence. With severe right ventricular outflow obstruction. Male    Phimosis. The other three abnormalities are a result of this one abnormality. Hipospadias and epispadias. Ectopia of the pancreas. Hirschsprung’s disease results from a failure of migration of neuroblasts that form the myenteric plexus. Congenital anomalies of the kidneys and the lower urinary tract        Agenesis. Atresia.157        Finally. The incidence is 1 per 5000 live births. The degree of cyanosis depends on the degree of pulmonary outflow obstruction. So. c) Palatoschisis (extend to the hard palate).

Infectious fetopathies   Infectious fetopathies can be connected with the influence of viruses and bacterium.5 m. Placenta abruption. Aplasia (Amelia) of legs. 2. fetus hypoplasia develops. Defects of placenta detachment are placenta adhesion (caused by deep implantation of blastocyst). Hondrodysplasia of fetus (lethal micromelia): a) Chondrodysplasia. In early period the impairment of tissue morphogenesis predominates. Hemorrhage may occur. In late period the reactive processes such as the disturbance of the blood circulation. Umbilical cord defects (its normal length is 0. inflammation. degenerations. and it presents a risk of placenta detachment during the delivery and intranatal death of the fetus.hydramnion (2000 ml and more). Amnion development defects: .0. This occurs at extragenital and genital maternal pathology. Fetopathies may be infectious and non-infectious.158 2. more than 0. Disturbance of the umbilical cord attachment to the placenta: 1. when the umbilical cord is attached to the membranes. If the length is less than 0. which may cause their rupture. Achondroplasia is a derangement in epiphyseal cartilaginous growth resulting in dwarfism. Sirenomelia. 3. h) Thickening of vertebra. The term comes from “siren” or “mermaid” because of the characteristic fusion of the lower extremities that results from a failure of normal vascular supply from the lower aorta in utero. regeneration.0.7 in it is long. placenta/fetus ratio is 1/5 -1/7. d) Saddle-like nose. the cord is short. The nose is troguently flat due to the aplasia of the vomer. Median facial clefts may also be limited to the upper lip. The placenta does not detach after the delivery. This develops as a result of Mastopathy. When the mass of the placenta decreases. Inflammation in placenta takes place. Oblique facial clefts extend from the upper lip to the corner of the eye. its causes are unknown. its vessels may be compressed with the parts of the fetus and amniotic fluid. or palate.5 . Fetopathy     Fetopathy is characterised by the combination of the impairment of tissue morphogenesis and reactive processes. e) Thickening of the tongue. compensative and adaptative processes.5 . and intranatal fetus death may occur. c) Open mouth. f) Short neck. presence of immune reactions. oligoamnios (500 ml and less). ante-. Defects of placental development        Placental hypoplasia (normal mass is 0. Defects of placenta localization are marginal and central placenta presentation in respect to internal uterus orifice. necrosis. when the foot and arm growth from trunk. Polyductyly is a malformation consisting of supernumerary finger development. b) Increase of the head. . Congenital malformations of the bone-cartilage system         Hondrodysplasias is characterized by the shortening and thickening of the legs. Phocomelia is underdevelopment of the proximal parts of legs. Membranous is pathological one.7 m). maxilla. Central and eccentric are normal types of attachment. Syndactyly is partial or complete fusion of several fingers. It may result in intranatal fetus asphyxia.7 kg). g) Hypoplasia of the thorax and lungs.

pseudocysts and free parasites. Early period is characterised by microcephalia of brain. DNA-containing virus enters the organism of the fetus from the mother through the placenta.large) is a virus infection involving salivary glands. the body mass is 4 .159  Pathologic morphology of fetopaties: a) Necrosis of parenhymatous organs and brain (rubella. toxoplasmolis). e) Hepato. kidneys. myocarditis. which is not observed in acquired cytomegaly. Productive necrotic rhinitis and uveitis in the retina. porencephalia with gliosis (consolidation of the remained brain tissue) and calcinosis. hemorrhage). myocardium. f) Jaundice. c) Hemorrhagic syndrome. Generalized infection in children is characterized by central nervous system (CNS) involvement. perivascular infiltration and calcinosis foci in the subependymal zone are observed in children. and the face as well as the soft tissues of the back and chest are swollen. jaundice. . adrenal gland.and splenomegaly. Hepatomegaly and cardiomegaly can be seen. Congenital toxoplasmosis       Congenital toxoplasmosis is a disease caused by toxoplasma. Generalized form of infection develops in the newborns. Outcome: death of fetuses and newborns or complication (paralysis.cell and megaios .6 kg. ulcers of the intestine. b) Formation of granulomas (syphilis. mental retardation. kidneys. pancreas. Noninfectious fetopathies   The main noninfectious fetopathies are hemolytic disease of the newborn. meningopathy. and thymus. Cytomegalic cells contain intranuclear formation resembling “owl’s eye”. During teratogenic termination period. The disease lasts several days (sometimes weeks). Microscopic examination demonstrates cysts filled with granular spheres. Encephalitis with formation of cytomegalic cells. Microscopic examination demonstrates erythroblastosis in the liver and spleen. The fetuses are infected through the maternal placenta. Late period occurs the foci of necrosis. cystosis) and systemic congenital defects of the bone and muscular tissues. Early fetopaties occur by the isolated congenital defects (pylorostenosis. megacolon. fetal mucoviscidosis. megaloureter. encephalitis in the whole brain. interstitial pneumonia. The main infectious fetopathies are cytomegaly and congenital toxoplasmosis. It ends with death caused by damage to vitally important organs. d) Immune reactions. These phenomena cause hydrocephalia. necrosis. the neck is short. liver. tuberculosis). cholestearosis in the liver. The signs of immaturity are observed in the mature fetus. As a rule. embryopathy incompatible with life occurs. Hemorrhages and necroses can also be observed in these organs. Diabetic fetopathy      Diabetic fetopathy is the disease of the fetus due to maternal prediabetes and diabetes. Cytomegaly       Cytomegaly (from cytos . The source of human infection is dogs and cats. agenesia. calcinosis and lymphohistiocytic infiltration in the liver. They can be found in the lungs. fibroelastosis of myocardium and diabetic fetopathy. and calcinosis in the brain. chickenpox. It develops as a result of hematogenic transfer from the mother’s organism. cytomegaly. Generalized form: besides GNS involvement there is hepato. intestine. Toxoplasma is a protozoic microorganism from tripanosomid family.and splenomegaly. The disease is characterized by formation of giant cells with intranuclear inclusions. and hydrocephalus. skin. ependymatitis. The skin is purple cyanotic with small point hemorrhages.

and progressive fibrosis. During the delivery of the child with fetopathy. Intestinum: obstruction by mucus (meconium ileus) Endocardial Fibroelastosis    Primary myocardial metabolic/enzymic defect and congenital malformations take place. Prematurity. and fibrosis. fat degeneration of the liver. Alcogolic syndrome of fetus           Alcogolic syndrome of fetus occurs by signs of embryofetopathy. respiratory insufficiency. Decreased pulmonary surfactant. Small cerebellum. The mutant gene may code for abnormal protein that affects chloride transport channels across epithelial membranes. The death is caused by antenatal and intranatal asphyxia. hyperplasia and hypertrophy of mucus-secreting cells. Hyperthelorism. birth injury. liver. hip-joint. cardiomegaly due to hypertrophy of left ventricle. epicanthus. Tight forehead. affecting both mucus-secreting and eccrine sweat glands throughout the body. glycogen accumulation in the tubular epithelium in the kidneys. atrophy of acini. Cleft palate. . General morphologic feature: obstruction by viscous mucoid secretions. Liver: bile ducts plugged by mucus with biliary obstruction and fibrosis. and hypoglycemia after birth stress. Frequent mental retardation. glandular atrophy. flat bridge. It is characterized by focal to diffuse. pancreas. Narrow palpebral fissures. Lung: Obstruction and secondary infection of air passages. hypoxia due to placenta vascular sclerosis and disturbance of placental circulation may occur.160     Microscopic examination demonstrates hypertrophy of islets of Langerhars. Salivary glands: progressive dilatation of ducts. short fingers. leading to viscid mucinous secretions and obstructive disease in lungs. kidney. small weight of fetus. Hyaline membrane disease may develop because synthesis of surfactant is disturbed due to disturbed lipid exchange (lipoproteid). cartilage-like fibroelastic thickening of the myocardium. Malformations of the heart. hydropic degeneration of the myocardium. A simple autosomal recessive syndrome. ptosis. Cystic fibrosis (Fetal mucoviscidosis)          A disorder of exocrine glands. squamous metaplasia. Death can be due to acute cardiac insufficiency in first days of life or due to chronic cardiac decompensation at connection (intercurrent) of the others diseases (pneumonia). Pancreas: plugging and dilatation of ducts. heterozygotes are unaffected. increased amount of B-cells.

Body length is less then 25 cm. 4. This fetus can live a life of independence. peeling. eclampsia). 10.  Stillborn is fetus without breathing and palpitation in the moment of the delivery. Antenatal period (from the 22nd week of gestation to the delivery). Overmaturity may lead to antenatal and intranatal death of the fetus due to hypoxia. 10. 3. umbilical cord. 3. 4. 6.161 PERINATAL PATHOLOGY Perinatal period means the period before and after the delivery. Beclard‟s nucleus of the distal femoral epiphysis is absent (in mature children it is 5 . amniotic membranes are usually staining with meconium (yellowgreenish color) as the fetus experiences intrauterine hypoxia.  Perinatal mortality is stillborn and infant mortality within the first 7 days of the life. 4. Lanugo hair on the face.  Delivery of a smaller fetus and until the end of 22 week of the gestation is called abortion. Amniotic fluid.  In the 22nd week of gestation the fetus must have the weight more than 500 g and the length of the body – 25-30 cm. Features of the overmaturity 1. Postnatal (neonatal) period (from birth to 7th day after birth). Microscopic examination of the organs in premature fetus allows determining the degree of prematurity: 1.  Liveborn is infant with signs of the breathing and palpitation. macerated. 7. 3. Dense long lobe of the auricle. Embryonic glomeruli are noted in the superficial layer of the cortical substance of the kidneys. Underdeveloped nails. 8. Thickening of interalveolar septa in the lungs. 5. Erythroblastosis foci are observed in the kidneys and liver. Early agein of placenta. 3. 6. Main cause of the overmaturity is late prime-gravide. Diseases of the genital tract of the pregnant women. Main causes of the prematurity: 1. 2. General hypotrophy of fetus. Perinatal period and the respective pathology and mortality is divided into 1. Soft lobe of the ear. Severe toxicosis of pregnancy (nephropathy. 2. 8. Signs of the placenta‟s agening (placental infarction. 7. Beclard‟s nucleus has 8 mm and more). Very dense cranial bones. 5. 2. Epidermis is dry. Placental insufficiency. . Overmaturity infant is defined as termination from the 41st week of gestation and later. Placental infections. In girls the labia minora and clitoris are not covered by labia majora. In boys the testes are not descended.7 mm). Premature infant is defined as those when the term of gestation is until 37 week. Acute and chronic infections of the pregnant women. Long nails. Intranatal period (during the delivery) begins in the moment of the delivery until the birth. petrification of the placenta). Soft cranial bones. yellow or yellow-greenish color. 5. 3. 2. Body weight is less then 500 gramms. 9. Rh antigens incompatibility. 7. 9. begining from the 22th week of gestation (196th day) to the 1st week of extrauterine life. 4. Causes and morphological features of prematurity and overmaturity of newborns Features of the prematurity 1. 6. Decreased amount of amniotic fluid. scrotum isn‟t wrinkled. 2. Sprout zone in the brain is widened.

 Chronic renal and pulmonary diseases of the mother. thyreotoxicosis). Degenerative changes in the liver. congestion. fetal factors import for all types of asphyxia. dark fluid blood in the heart chambers. disproportion between the fetus’ head and delivery tract of mother (narrow pelvis. Causes of asphyxia I.  Infections of newborn. such as:  Maternal cardiovascular diseases. brain. adrenal glands.  Late toxemia of the pregnancy. II. meconium. myocardium.  Multiple gestations.  As a rule. postnatal asphyxia is a continuation (or consequence) of intranatal asphyxia.  Aspiration pneumonia. postnatal asphyxia develops.  Background: progressive fetal asphyxia.  When during the delivery CNS (including respiratory center) is damaged or under the influence of intrauterine hypoxia. Prominent among such fetal conditions are chromosomal disorders. III.  Complications of the delivery: weakness of the delivery processes. the disturbance of the psychomotor development and cardiosclerosis may develop. fetus breech presentation.  A birth injury of the spinal cord and central nervous system.  Prolaps of the umbilical cord. development of syndrome’s disseminated intravascular coagulopathy on the other hand. 2. Causes of antenatal asphyxia associated with maternal factors resulting in decreased placental blood flow and placental insufficiency. serous membranes and mucosa. kidneys.  Placenta previa. and congenital infections. Causes of postnatal asphyxia associated with disturbance of the breathing. heavy cigarette smoking).  Accidental hemorrhage. Causes of intranatal asphyxia associated with defects of the placenta and complications of the delivery:  Pretermed placental separation. to inadequate of the delivery and may lead to birth injury. umbilical cord winding round the neck of fetus. Intranatal asphyxia (asphyxia neonatorum) arises during delivery.  Brain trauma or edema with suppression of the respiratory center. If such children survive.162 The most important diseases of perinatal period Asphyxia (anoxia)   Asphyxia means lack of oxygen and excess of carbon dioxide in the blood suppling. Aspiration of amniotic fluid containing skin epithelium. congenital anomalies.  Cord knots. the fetus makes the first inspiration intrauterinally (carbon dioxide stimulates the respiratory center) and amniotic content is aspirated.  Placental abruption. resulting in fibrin thrombi in the microcirculatory vesells. 3. Edematous syndrome in inner organs and cavities. Asphyxia may be 1. Postnatal asphyxia (asphyxia neonatorum) is called asphyxia of the newborn and arises after delivery in result of illnesses of newborn.  Social causes (narcomania. Antenatal asphyxia is called the intrauterine asphyxia of the fetus (fetal asphyxia) and arises during pregnancy.  Endocrine diseases (diabetes mellitus. rupture the short umbilical cord. lanugo. The main clinical-morphological syndromes of asphyxia      Hemorrhagic syndrome: petechial hemorrhage in brain. alcohol. In this case the alveoli cannot spread after the delivery. large fetus).  Severe infections of the mother. Besides. Pneumopathies . because they lead to an inadequate supply of nutrients from the mother.

CNS (central nervous system) malformations and intrauterine hypoxia. desquamated keratotic squames. Slitlike air spaces. contraction and lack of pulmonary surfactant.and extraalveolar hemorrhages develop. Microscopic examination demonstrates collapsed alveoli. which lead to asphyxia of newborn. high diaphragm and spinal deformities. 4. while the newborn infants with weak respiratory action develop incomplete expansion of the lungs and clinical atelectasis. 3. They occur as a rule in preterm children. vascular permeability increases due to hypoxia. Obstructive/absorptive collapse.. Heart and great vessels fully exposed. mucus. The disease of hyalin membranes often accompanies this condition. Pressure from outside causes compressive collapse e. Aspiration during birth of blood clot and amniotic fluid when the amniotic debris (i.e. Respiratory distress syndrome of newborn (RDS)     RDS is one of the most common life threatening complications to confront the newborn infant. Feeble respiratory efforts secondary to immaturity of the lungs and sceletal muscles (primary atelectasis). obstruction.g. including: 1. RDS is also known as hyaline membrane disease (HMD). asphyxia develops quickly. proteinaceous precipitate. and the newborns die within the period of 24 . bronchiectasis. by viscid mucus secretions in bronchial asthma. bronchial tumors and aspiration of foreign bodies. the children die because of respiratory insufficiency.   While pulmonary collapse or primary atelectasis is the term used for reduction in lung size of a previously expanded and well-aerated lungs. . There is atelectasis. Microscopic examination shows intraalveolar pink fluid. This type occurs due to localised fibrosis in lung causing contraction followed by collapse.g. Macroscopicall appearance of atelectasis:     Large plural space. hemothorax. highlighting one of the major pulmonary anatomic findings in this disease. Diffuse edema and large intra.36 hours. 3. The common causes are prematurity. lanugo hairs. Atelectasis    Atelectasis in the newborn or primary atelectasis is defined as incomplete expansion of a lung or part of a lung. by massive pleural effusion. Excessive sedation of the mother with consequent depression of respiration in the infant. Obstruction of a bronchus or many bronchioles causes absorption of oxygen in the affected alveoli followed by collapse e. intrathoracic tumor. development of the hyaline membranes. Compressive collapse. Autopsy demonstrates large lungs with hemorrhages. Lungs are involved. Stillborn infants have total atelectasis. 2. Brain injury with failure of the central respiratory centers. Secondary atelectasis in children and adults may occur from various causes such as compression.163 Pneumopathies are noninflammatory pulmonary diseases. Edematous hemorrhagic syndrome       It is associated with asphyxia when the lung capillaries are overfilled with the blood. cerebral birth injury. Collapse may be of the following 3 types: 1. pneumothorax. Contraction collapse. chronic bronchitis. Small and collapsed lungs against vertebral column and are of cyanotic color. 2. It can have many origins. edematous-hemorragic syndrome. hemorrhages. Difficulty of the breathing takes place.

and random alveoli. Although of normal size. congested and heavy lungs. Birth injury . it also brings to the surface the exquisite fragility of the immature neonate.  In infants who survive more than 48 hours reparative changes are seen in the lungs. total or disseminated atelectasis of the lungs (primary) may develop as the lungs are filled with aspiration masses and do not spread. Pneumonia in newborn         Pneumonia of newborns may occur in uterus (in ante. The alveolar epithelium proliferates under the surface of the membrane.5 hours. mostly the proximal alveoli. Microscopic examination:  The alveoli are poorly developed. But more important than all these by an order of magnitude is the idiopathic RDS. The most frequent are coccal pneumonias. airless. and it maintains alveolar expansion by varying surface tension with alveolar size. klebsiella. Most important among these are patent ductus arteriosus. and is often observed at overmaturation.  The membranes are largely made up of fibrinogen and fibrin admixed with cell debris derived chiefly from necrotic alveolar-lining pneumocytes. Infants who recover RDS are at increased risk for developing a variety of other complications stiff. The atelectasis results from the clearance of the fluid without its replacement by air. This may explain why infants of diabetic mothers have a higher risk of developing RDS. the first breath of life requires high inspiratory pressures to expand the lung. including cortisol.  In early stage of RDS the necrotic cellular debris is present in the terminal bronchioles and alveolar ducts.  Interstitial and intraalveolar edema. Surfactant reduces surface tension within the alveoli so that less pressure is required to hold alveoli open. and necrotizing enterocolitis. In massive aspiration. Amniotic fluid may be infected or may contain meconium. the necrotic material becomes incorporated within pink hyaline membranes that line the respiratory bronchioles. The etiology is different. Surfactant synthesis may be suppressed by the infants of diabetic mothers‟ compensatory high blood levels of insulin. and colon bacillus. Morphological features of RDS Gross examination of the lungs. although the high technology of today saves many infants with RDS. intraventricular hemorrhage. Corticosteroids induce the formation of surfactant lipids and apoproteins in fetal lung. Aspiration syndrome is the first inspiration done in uterus. insulin. The disease often develops against the background of amniotic fluid aspiration both infected and not infected. reddish purple like the liver. prolactin. they are solid.  Later. leukocytic and monocytic infiltration of alveolar tissue involving the bronchioles and bronchi are observed. small-focal pneumonia develops. which counteracts the effects of steroids. alveolar ducts. The role of glucocorticoids is particularly important. The most often in newborn the aspiration pneumonia develops. With deficiency of surfactant the lungs collapse with each successive breath as it did with the first.164 and blood) blocks ventilatory function. and thyroxin. It is synthesized by type 2 alveolar cells most abundantly after the 35 week of gestation in the fetus. in 24 hours it turns into confluent pneumonia. Surfactant synthesis is modulated by a variety of hormones. The syndrome is due to hypoxia. Autopsy demonstrates stiff. If the child survives for 3 . and those that are present are collapsed. Elements of amniotic fluid are determined in the exudate. The fundamental defect in RDS is a deficiency of pulmonary surfactant. Thus. where it may undergo partial digestion or phagocytosis by macrophages. which may be desquamated into the airspace. At birth. Asphyxiating coils of umbilical cord about neck of the infant. as well. Microscopically. It is considered that intrauterine pneumonia is responsible for the death during the first 1 -3 days of life. and they usually sink in water. 5.and intranatal periods) as well as after the birth.

under the ependyma of the lateral ventricles with rupture to the ventricles. tumors. that they hardly merit the designation “birth injury”. even in normal uncomplicated births. Epidural hemorrhages are located between the bones of the skull and the dura mater (inner cephalohematoma). The blood is accumulated under the dura mater on the brain substance. The state of failure of the delivery‟s dynamic: a) Precipitated delivery. wounds) c) Tumors of maternal passages d) Oligoamnios. it may extend across the suture lines. Causes of birth injury are due to: 1. 3. Visceral hemorrhages: subcapsular hematomas and hemorrhage from spleen. and swelling at the site where the head being to enter the lower uterine canal. Because the fluid accumulates in the subcutaneous tissue. liver. which occurs when obstetric manipulations are carried out. When the fetus inherits red cells antigenic determinations from the father that are foreign to the mother. Pathology         Cephalogematoma is produced by an effusion of blood between the pericranium and one of the bones of the head. anomalies. The most frequent course of the death in intracranial injury is rupture of the falciform process and cerebellum tentorium.165    Birth injuries constitute important causes of illness or death in infants as well as in children during the first years of life. c) A lot or little of amniotic fluid. veins. b) Prolonged delivery. leading to the hemolytic disease in . or the extraction of the after-coming head. The state of the fetus: a) Embryopathy. The most severe intracranial injury is hemorrhage to the meninges and brain substance. The most often fractures of the spine (often fatal to the life). bone’s skull. stomach due to fracture. The state of the maternal passages: a) Rigidity of the birth canal tissue. congestion. 4. hydramnion. 2. When infected. It disappears slowly. b) Pelvis defects (narrow pelvis. c) Prematurity (the tissues are easily ruptured) and overmaturity (hypoxia increased vulnerability of the fetus). 2. Birth injury should be differentiated from obstetric injury. 3. Intracerebral cephalohematomas are the hemorrhages to the vascular plexi of the brain. Subdural cephalohematomas occur in rupture of the falciform process and cerebellum tentorium. it may become a source of purulent meningitis. fracture of the clavicle. It occurs in rupture of the falciform process. giving rise to a usually circular area of edema. Morbidity associated with birth injury may be acute or the result of later-appearing sequels. Subarachnoid cephalohematoma is localized between the arachnoid and pia mater. a maternal immune reaction may occur. b) Fetopathy. cerebellum tentorium. The first refers to progressive accumulation of the interstitial fluid in the soft tissues of the scalp. Birth injuries are damage to the fetal tissues and organs with mechanical forces during the delivery. femoral and humerus bones occurring in large fetuses. Hematoma of the sternomastoid muscle may follow traction on the head during the birth of the shoulders. All hemorrhages are divided into 1. Hemolytic disease of the newborn (HDN) or Erythroblastosis fetalis   Erythroblastosis fetalis is defined as a hemolytic disease in the newborn caused by ABO-group and Rh incompatibility between mother and child. rachitic pelvis. Caput succedaneum and cephalhematoma are also so common.

 Subtle medial thickening of small pulmonary arteries and brain-stem gliosis suggests chronic hypoxia. there is transudation in the cavities. The cells stain by yellow color. Ninety per cent of SIDS deaths occur in the first 6 months of life. and even in the heart. transplacental passage of the maternal antibodies into the fetus. spleen. the child is born alive with one of the forms of HDN. Morphology A variety of changes of uncertain significance. Congenital hydrops (edematous form) is characterised by edema of skin. lymphatic nodes. “the apnea hypothesis”. when the cause of death cannot be explained even after autopsy. Sudden infant death syndrome (SIDS)      Included here since some cases of SIDS may be related to congenital cardiac disorders. in turn. defects of CNS development (including complete idiopathy) may occur in future. lungs. such as lymph nodes. Jaundice is absent. 2. Among innumerable hypotheses. The most serious threat in this disease is central nervous system damage known as kernicterus. Icterus gravis (severe jaundice of the newborn) is evident by the end of the first day. . not always present and of diverse nature. meninges and brain substance. Any of the numerous red cell antigenic systems may theoretically be involved. . Often there are minor antecedent respiratory tract infections. kidneys.  In children who survived HDN.Disturbed regulation of respiration. and the child may survive without further complications. Probably a multifactorial entity or common end point of diverse derangements.  In early massive immunization of the mother. spleen. In jaundiced infants.  . The deaths occur without a struggle during the night after a period of sleep. A hemoliyic disease that may appear during gestation or shortly after delivery.  Histologically in all forms.Inherited disorders of fat oxidation. they have the signs of erythroblastosis and hemosiderosis. and possibly other tissues. those favored are: . Anemia neonatorum (hemolytic anemia) is frequent in immature fetuses. The disease develops quickly. In the mildest form. Defined as sudden and unexpected death in a previously basically well infant. on the 5th .Defective regulation of body temperature with resultant acute malignant hyperthermia. The skin and mucous membranes are pale.Unsuspected intestinal infection with Clostrium botulinum.  When the mother’s immunization is later and more moderate. most between the ages of 2 and 4 months.7th month of gestation. 3. Hepatosplenomegaly take place. Causes of death are unknown. Signs of immaturity of organs in mature newborns can be found. . The fetus dies before the birth. the diagnosis of erythroblastosis depends on the identification of abnormally increased erythropoetic activity in the infant. There are bilirubin infarcts in the kidneys. but the major antigens known to induce clinically significant immunologic disease are the ABO and certain of the Rh antigens (Rh negative mother and Rh positive fetus) The resultant fetal hemolytic reaction may cause mild-to-severe disease in the newborn. More severe hemolysis dives rise to jaundice and other features associated with hemolytic anemias.166    the infant. the unconjugated bilirubin appears to be particularly toxic to the brain tissue. The brain is enlarged and edematous and. Basis to such a phenomenon are leakage of fetal red cells into the maternal circulation and. when sectioned. The red cells series in the marrow is hyperactive and extramedullary hematopoesis is almost invariably present in the liver. early fetopathy develops. . Abnormalities in the myocardial conduction system have been observed. or even death. the anemia may be only slight. and kidneys. subcutaneous fat. Microscopically: erythroblastosis in the liver. The liver and spleen are enlarged.Cardiac arrhythmias. Classification of erythroblastosis fetalis 1. is found to have a bright yellow pigmentation (kernicterus).

Also seen are retention of fetal hemoglobin. . extramedullary.167   Right ventricular hypertrophy may be secondary to pulmonary vascular changes or a primary anomaly.

parainfluenza viruses. According to the duration there are    Acute. bacteria.infectious diseases typical only for people. The route of the infection from the primary focus or complex may be lymphogenic. Infections with different mechanisms of transmission. . Infections of the external integument. Bacterial. and serotypes. These include: 1. lymphangitis and lymphadenitis. Latent. Each infectious disease is characterized by local changes in the portal of entry of infectious agent. fungi). one can observe formation of a primary infectious complex consisting of a primary affect. Respiratory. which become the place of causative agent multiplying. contact. of different families. Blood (transmissive) transmitted by blood-sucking insects. climax and extinction). Orthomyxoviruses (influenza A. Classification according to the mechanism of transmission:      Intestinal. According to the etiology they are divided into       Viral. In infectious. Infectious diseases are classified according to a number of signs. A number of common changes (rash. vasculitis. Rickettsiosis. Biological classification:    Anthroponoses . Clinical-morphological characteristics of infectious diseases         Each infectious disease has its own causative agent. hyperplastic processes in the lymphatic nodes. Antropozoonoses . measles virus. Chronic. Fungal. Infectious diseases have a number of common features. and perineural. which can be isolated from the blood or excreted materials of the patient. spleen. and C – RNA virus). {subcutaneous fat and muscles). bone marrow. Paramyxoviruses (respiratory syncytial virus. intracanalicular. Biocenoses . Parasitogenic.infectious diseases that can develop both in people and animals. hematogenic. B. Herpesviruses (varicella-zoster virus).a group of anthroponoses and anthropozoonoses transmitted through the bites of insects. The course of the infectious disease is divided into incubative and prodromal periods and the period of main manifestations of the disease (phases of increase of the signs. Infections can be either exogenic or endogenic. inflammatory processes in the interstitial tissue and degenerative changes in the parenchymatous organs) are observed in infectious diseases. species. Protozoa and helminths cause invasive diseases.168 INFECTIOUS DISEASES Infectious diseases are those caused by infectious agents (viruses. VIRAL DISEASES Respiratory disorders are caused by a wide variety of viruses. Protozoal. mumps virus) 3. Infectious diseases are chiefly cyclic. Adenoviruses. 2. 4.

Patients with viral influenza during the third trimester of pregnancy. The peculiarities of viral diseases 1. 8. causes epidemics. Picornaviruses (rhinoviruses. At this stage acute bronchitis or tracheitis develops. echoviruses. The virus invades the bronchial and alveolar epithelium and endotheliocytes of the capillaries and multiplies there causing primary viremia. adenovirus infection). adenovirus infection. while the patient appears to be getting well. and persons with valvular heart disease or chronic bronchopulmonary disease all have increased susceptibility to bacterial superinfection. Being highly contagious. Cytomegalovirus. the most common cause of viral pneumonia in adults. c) Integration of the virus and the cell genome without considerable destruction of the cell (hepatitis B. headache. necrosis and desquamation of the bronchial epithelium. 4. but not epidemic influenza. The morphological manifestations of cell-virus interrelations are: a) Cytolytic effect of the virus on the cell (influenza). viruses cause epidemics and pandemic. and acute toxic state. The development of the virus in the cells causes degeneration. 3. The epithelial cells die. rhinovirus. b) Formation of inclusions in the cell (influenza.4 days. Immunomorphological study with antisera to the definite strain of viruses is performed in the smears from the mucous membrane of the upper respiratory tract or in the tissue (if it is autopsy material). These are the first clinical signs of the disease. infects animals and man and produces pandemics. reovirus). muscle pains. Influenza viruses are highly contagious and afflict people of all ages and have 3 types: a) Influenza A virus. the virus leaves them and invades ones more the bronchial and alveolar epithelium. but pulmonary complications such as influenza pneumonia and secondary bacterial infection of the lung may complicate and prolong course. and coxsackieviruses). The variety of viruses determines the lesion of specific cells due to the virus trophism. Herpes simplex virus (HSV). d) Proliferation of target cells (smallpox). Acute respiratory viral infection (ARVI) The term denotes a group of acute inflammatory diseases caused by pneumotropic viruses (Influenza. The incubation period is 2 . parainfluenza. e) Giant-cell transformations (measles). which in turn causes secondary viremia. Morphology Clinical-morphological forms of influenza .). sore throat. Dry cough and nasal discharge are present but usually are overshadowed by systemic symptoms.169 5. c) Influenza C virus causes sporadic upper respiratory infections. chemotaxis. Human respiratory coronaviruses. 2. The duration of the disease depends both on the type of the virus and the reactivity of the macroorganism and can be acute. and may have long-term sequelae. In this case bright fluorescence is seen under the microscope. the aged. In uncomplicated cases the illness lasts a few days. slow. chronic. 6. stasis. 7. fever. The character of the cell receptors determines trophism. Influenza viruses are transmitted by aerosols generated by coughing and sneezing. Influenza has significant mortality and morbidity. and is associated with Reye‟s syndrome in children and pneumonitis and croup in infants. which contributes secondary (often bacterial) infection. At present differential diagnosis of ARVI is not difficult. hemorrhage) and immunedepressive action (phagocytosis inhibition. Superinfection usually occurs 1 to 5 days after the onset of the viral illness. respiratory sincitial virus. etc. Its manifestations are vasoparalytic action (plethora. HIV infection). Influenza          Influenza is a disease characterized by abrupt onset. b) Influenza B virus is apparently restricted to man.

pneumofibrosis and other chronic lung diseases develop. hyperemia. Lungs appear as (“large variegated (motley) influenza lung”).  Interstitial pneumonia develops. as well as encephalitis. bronchiectasis. might be found as postmorten examination of fatal cases. The infection involves only the upper respiratory tract. 2. Slight influenza is characterized by the lesion in mucosa of the upper respiratory tract (edema.  The duration of the disease is 3 -4 weeks.  The patients die on. diffuse hemorrhagic necrotizing pneumonitis with pulmonary edema. trunk dislocation develop in the brain. empyema). Replication is restricted to the respiratory tract and moderate intoxication. occurring endemically throughout the year. These are microcolonies of the virus.  Encephalitis. Mild influenza is characterized by involvement of the pathological processes in mucosa of the bronchi. pulmonary complications (pneumothorax. serous inflammation). serous meningitis. Individual cells show pycnosis of the nuclei and loss of cilia. 3. hemorrhagic lung edema may develop.  Microscopically. but they are uncommon. 2. brain trunk dislocation. They are transmitted by inhalation of droplets of aerosols. bronchiolitis. Pulmonary complications. measles virus. and infiltrated with mononuclear cells.  The histopathologic features include a necrotizing tracheitis and bronchitis. brain edema.  Desquamation of the alveolocytes lead to decrease of surfactant and development surfactant-depending atelectases in the lungs. Interalveolar septa are thickened due to proliferation with lymphocytes and macrophages. tracheitis and bronchitis occur. Hemorrhage to the brain and internal organs develop.170 1. Paramyxoviruses    Paramyxoviruses (parainfluenza viruses. the picture is indistinguishable from that of ordinary bronchopneumonia or lobar pneumonia. except in some infants in whom the primary infection may also involve the larynx. The duration of the disease is 5 . The pathology of the disease resembles slight influenza. cerebral hemorrhages. they also can be determined with immunomorphological method. Paramyxoviruses are spherical enveloped viruses that contain single-stranded RNA. Parainfluenza viruses are spread principally by direct contact or by large droplets (in contrast to the spread of influenza virus by inhalation of small droplets). and a fluid exudate in the alveolar spaces has a hyaline membrane appearance. there is pronounced sloughing of the bronchial epithelium into the bronchial lumens. the 4th . bronchioles and lungs. abscesses are presence also.  Lungs are dark red and firm with interstitial emphysema (pink color) that may extend into the mediastinal tissue. Laringitis.  Ciliated epithelial cells are destroyed and goblet cells and mucous glands disrupted.  Obliterating bronchitis. Necrotic foci. Infants are especially susceptible.5th day of hemorrhage to vital centres and of acute respiratory and cardiovascular insufficiency.  If bacterial superinfection occurs. distended. brain edema. Parainfluenza viruses infection (Types l-4)       Type 3 parainfluenza is the most prevalent of the parainfluenzas.  Degeneration and inflammation in the nodes of the vagus and sympathetic nerves cause neuritis. respiratory syncytial virus.  Myocarditis and pericarditis. There is often severe inflammatory edema.  Bronchioles become thickened. and cardiovascular and pulmonary insufficiency.  Besides serous hemorrhagic bronchitis and pneumonia. mumps virus) are important causes of respiratory disease in infants and young children. Severe toxicosis. Severe influenza is characterized by the complicated duration of disease and occurs by: 1. trachea.6 days with following convalescence.  The death is caused by intoxication. and bronchioles. .

the viruses multiply in the epithelium of the intestine (diarrhea). conjunctivitis and regional lymphadenitis. tracheobronchitis. kidneys. Susceptibility is also increased in elderly or immunocompromised patients. which in turn causes immune reconstruction. Slight AVI is characterized by acute rhinitis. but intranuclear inclusions are not present. tonsillitis.  The course may be slight and severe. pneumonia due to the secondary infection. edema. and cell debris. This agent accounts for about one-third of hospital admissions for pneumonia and for up to 90% of those admitted for bronchiolitis. Edema in larynx may lead to development of the “false croup” and asphyxia. hemorrhage. There is interstitial pneumonia. sepsis. sinusitis. 1. conjunctiva and spotted papular eruption on the skin. Severe AVI is caused by generalization of the virus and secondary infections. angina. ganglious cells of the brain with development of inflammation and hemorrhages. annual epidemics occur in midwinter (January-March). laryngitis. abdominal lymphatic nodes as well as conjunctivitis. Histopathologic features include necrotizing bronchitis. types 4 and 7) are common causes of acute respiratory disease and adenovirus pneumonia in military recruits coming together for the first time for basic training. so that the damaged bronchiole resembles a thrombosed blood vessel. Two distinctive types of intranuclear inclusions . bronchopneumonia. bronchiolitis. sinusitis. Adenovirus infection  Adenovirus infection (AVI) is caused by DNA-containing adenovirus. 2. In generalized infection. and interstitial pneumonia. The virus enters the upper respiratory tract and eye conjunctiva. In many cases irregular intracytoplasmic inclusion bodies are seen in alveolar and bronchiolar epithelial cells. mucus.  Adenoviruses (subgroup B.are scattered throughout the lesions but primarily involve bronchiolar epithelial cells and alveolar lining cells. appearance of polymorphic cells with one or several picnotic nuclei (multinucleated cells). Secondary infection is characterized by suppuration and sepsis. and otitis. Histopathologic features of adenovirus pneumonitis include necrotizing bronchitis and bronchiolitis. This is characterized by invasion of the upper respiratory tract. The cause of death is pneumonia. Respiratory Syncytial Virus infection        The respiratory syncytial virus is the most common cause of viral pneumonia in children under 2 years of age and is a common cause of death in infants aged 1 to 6 months. Measles Measles is an acute highly contagious infectious disease characterized by catarrhal inflammation of the mucous membranes of the upper respiratory tract. and mononuclear inflammatory infiltrate. lymphoid tissue of the intestine.171    The characteristic signs are tracheal and bronchial epithelium proliferation. . The infiltrate is purely mononuclear (predominantly lymphocytes). acute pharyngitis. Complications are secondary infection. with necrosis and desquamation of the epithelium Sloughed epithelial cells are subsequently mixed with mononuclear cells. Etiology and pathogenesis    The causative agent of measles is an RNA-containing virus transmitted by inhalation (airdroplets). liver.smudge cells and Cowdry type A intranuclear inclusions . with areas of consolidation showing extensive necrosis.  Complications: otitis. Degenerative changes in the epithelium of the mucous membrane and hematogenous spread are accompanied by short viremia resulting in dissemination of the virus in the lymphoid tissue.  Adenoviruses (subgroup C) are also important causes of chronic pulmonary disease in infants and young children. pancreas. In temperate climates of the northern hemisphere. The death is caused by asphyxia and pulmonary complications. asphyxia.

 The mucous membrane is swollen. affected glands are enlarged. Morphology  Catarrhal inflammation in the mucous membrane of the mouth. A transient viremia spreads the mumps virus to other glands and the central nervous system via the choroid plexus. Complications is accompanied with the secondary viral and bacterial infection. pancreas and central nervous system.  The disease involves internal membrane of the bronchi (endobronchitis). They are of great diagnostic significance. It looks like whitish spots called Belsky-Filatov-Koplik spots. middle layer (mesobronchitis). serous meningitis and meningoencephalitis. plethoric. Exanthema in the form of large-spot papular eruption first appears on the skin behind the ears. neck. the eruption appears. which develop before the eruption on the skin. the gland interstitium is edematous and diffusely infiltrated by histiocytes. the mucous secretion is increased. mononuclear cell infiltration. Neutrophils and necrotic debris may fill the ductal lumen and cause focal damage to the ductal epithelium. body.  Measles is characterized by metaplasia of mucosa epithelium into multilayer squamous epithelium observed in early periods (5th . Incubation period is 9-11 days. The duration of the disease is 2 . conjunctiva develops. salivary glands. and external layer (peribronchitis). When the eruption disappears. Mumps   Mumps virus causes a transient inflammation of the parotid glands and rarely of the testes. and are moist. glistening. and focal hemorrhages has been revealed.172    Viremia becomes more expressed and prolonged.  Varies from pure interstitial (viral) pneumonia to lobar (bacterial) pneumonia. There are often pathognomonic multinucleated giant cells (Warthin-Finkeldey cells).  Viremia and generalization of the process result in enanthema and exanthema: 1. have a soft consistency. greyish-yellow. Such panbronchitis is the source of bronchiectasis. and inner surface of the extremities. trachea. and lacrimation. and hyperplasia of distal bronchial cells. Morphology     In mumps (parotitis). Mumps viruses are spread by inhalation (air-droplets) and multiply within respiratory epithelial cells.  Severe cases are accompanied by necroses. which decreases the barrier function of the epithelium. and purulent pleurisy. bronchi. lymphocytes. In immunocompromised patients measles pneumonia may occur without rash and is often fatal.6th days of the disease). which is bilateral in 70% of cases. the mucosa becomes dull. The disease produces stable immunity. In mumps orchitis. The involvement of peribronchial lung parenchyma causes the development of peribronchial pneumonia and chronic disease of the lungs resulting in pneumosclerosis. Microscopically. Complications: atrophy of testis with azoospermia development. the virus cannot be found in the organism.  The edema and necrosis of the laryngeal mucosa can develop reflex spasm of its muscles with asphyxia (so called “false croup”). 2. and reddish brown on cut-section.  Moist gangrene of the soft tissue of the face (noma) is rarely observed at present. then on the face. lung abscess.3 weeks. The death of the patients with measles is associated with pulmonary complications and asphyxia in “false croup”. testicular edema. intranuclear and intracytoplasmic inclusions. small lumps are seen on its surface. . cough. the involved lungs look like grey-yellow foci resembling tuberculosis ones. and T cells in lymph nodes. Modern seroprophylaxis and vaccination have resulted in considerable reduction of the frequency of disease and death rate.  Destructive (necrotic or purulent-necrotic) panbronchitis can occur.  On incision. and plasmocytes that compress acini and ducts. Enanthema is noted on the mucous membrane of the cheeks against the lesser lower molars. which is accompanied by rhinitis.

. lymphopenia and hypergammaglobulinemia develop. Immunodeficiency leading to opportunistic infections or tumors (AIDS).Chronic active viral infection with immunocomplex disease (such as thrombocytopenic purpura). diarrhea. There are AIDS-ihdicating diseases (according to WHO)   Candidosis of the esophagus. Clinical picture      Incubative period of HIV-1 at sexual way of infection lasts from 2-3 weeks to 2-3 months. Unexplainable body weight loss (by 10% or more). i. HIV can also be spread via blood or blood products. nephritis. HIV is a sexually transmitted disease. 4. lungs. Lymphopenia. cough. 2. Persistent generalized lymphadenopathy. vomiting. nausea. The early signs of the disease are increase of temperature. The patients are infective during all the life. sometimes I year. This is the point at which the characteristic opportunistic infections and neoplasms of AIDS appear. Extrauterine cryptococcosis.173  The death of the patients with mumps is associated with central nervous system involvement. meningoencephalitis. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. then the stage of clinical AIDS has been reached. Infection is aided by Langerhans cells in mucosal epithelial surfaces. The signs of suspected AIDS (according to WHO)      Prolonged fever of unclear origin. pneumonia. most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Acute viral infection sometimes associated with immune complex disease. Chronic encephalopathy caused by HIV 6. Pneumonia of unclear origin resistant to standard therapy.e. ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) Etiology and pathogenesis           Human immunodeficiency virus (HIV) is the causative agent for AIDS. When HIV infects a cell. gastritis. presence of antibodies to HIV infection with simultaneous loss of body mass (20 kg during the last 2-3 years). Chronic active viral infection with constitutional symptoms or AIDS related complex. When the CD-4 lymphocyte count drops below 200/microliter. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. duodenitis. HIV is a retrovirus that contains only RNA. After those lymphatic nodes of different localization as well as the liver and spleen enlarge. which are released. Next stage is appearance of oncological diseases or generalized infection. Chronic diarrhea (not less than 2 months). The source of HIV is a sick person or a virus carrier. bronchi. It is this proviral DNA that directs the cell to produce additional HIV virions. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. which can become infected. The signs of the disease also depend on the lesion in the definite system. it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. 3. trachea. 5. The clinical spectrum of HIV infection is now recognized to comprise 1.

especially the AIDS-dementia is an important cause of morbidity in patients in advanced stages of infection. These “burnt-out” lymph nodes are atrophic and small and may harbor numerous opportunistic pathogens.  Non-Hodgkin’s lymphomas. lymphatic nodes in the patients over 1 month). Morphology At autopsy the gross pathology of AIDS can be split into three general categories as follows: 1. the frenzy of B-cell proliferation subsides and gives way to a pattern of severe follicular involution. They are very aggressive and respond poorly to therapy. mainly seen in white matter. plaques. involving the nodes as well as extranodular sites. In the empty-looking lymph nodes and in other organs. Toxoplasmosis of the CNS in the patients aged over 1 month. such as the liver. These cells are derived from macrophages and support viral replication. Cytomegalovirus lesion of some organs (except for the liver. and the organized network of follicular dendritic cells is disrupted. Infection caused by herpes simplex.  With disease progression. often in the brain. and besides multinucleated cells they include diffuse pallor of the white matter and vacuolar myelopathy. basal ganglia and brain stem.174        Cryptosporiosis with diarrhea for more than 1 month.  Neurologic complications. microglial activation and gliosis in CNS grey matter. 2. spleen. 3.  Lymphocytic meningitis is seen in patients around the time of seroconversion and is defined as occurring in the absence of any demonstrable opportunistic pathogens.  The early stage of HIV is characterized by enlarged lymph nodes and the follicular hyperplasia.  Diffuse poliodystrophy is the term applied to neuronal loss. The germinal centres may even become hyalinised. gastrointestinal tract. spleen and thymus also appear to be “wastelands”.  Cerebral vasculitis is seen most prominently in childhood HIV disease of the brain. These are thus markers of productive infection. Infections caused by opportunistic pathogens. persisting more than I month in the patients aged over 1 month. Malignant lymphomas seen with AIDS are typically of a high grade and extranodal. are primarily high-grade diffuse B-cell neoplasms. .  In later stages of AIDS. Pneumocyst pneumonia. The pathologic abnormalities in patients with AIDS-dementia complex are variable. or nodules over the skin and can be diagnosed with skin biopsy. Multinucleated cells in the brain are found in a subgroup of patients with severe disease.  HIV encephalitis is a multifocal process characterized by inflammatory foci including multinucleated giant cells. Visceral organ involvement eventually occurs in 3/4 of patients with KS. the presence of infectious agents may not be readily apparent without the application of special stains. The morphologic manifestations of profound lymphoid depletion. and bone marrow. Unusual neoplasms such as Kaposi‟s sarcoma and high-grade lymphoma. Kaposi‟s sarcoma (KS) produces reddish purple patches. The follicles are depleted of cells. All histopathlogic abnormalities are most prominent in the subcortical structures.

Diphtheria is amenable to virtually complete eradication by routine immunization with diphtheria toxoid. The soft tissue of the neck is swollen. Diphtheria in the pharynx. gram-positive rod Corynebacterium diphtheria. paretic dilatation of the vessels with disturbance of their permeability. The exotoxin causes local necrosis of the epithelium. Diphtheria in the pharynx Local changes:     Cervical adenopathy seems out of proportion to the pharyngeal lesion. Parietal thrombi can be observed. General changes are accompanied with toxinemia and appear: 1. become gray or black. variegated. The disease is more common in children. 2. excretion of the exotoxin from the organism is accompanied by the damage of tubular epithelium of the kidneys. usually over the tonsils. the genital tract.  Toxic myocarditis develops in the heart. nervous systems and adrenal glands. the edema is considerable and can involve the anterior surface of the chest. but particularly in the tropics. edema of the tissues and release of fibrinogen from the vascular bed. Diphtheria toxin is particularly toxic to myocardium. the muscle is dull. The cavities of the heart are dilated. Morphology Clinical-morphological classification 1. Toxic produced locally by toxigenic strains of C. Alterative and interstitial forms of myocarditis are distinguished. however. esophageal. Etiology and pathogenesis            Diphtheria is caused by a slender. at present the disease is more frequent in children over 7 years. flabby. . or gastric mucosa is involved as well. Incubation period is 2-10 days. Rarely forms of diphtheria. or cultism. Diphtheria in the respiratory tract. from which the process often extends to the nose or larynx). complacency. The diphtheria bacillus multiplies at the site of attachment on the mucosa and excretes exotoxin. In severe toxic forms. with the accumulation of blood. diphtheriae is responsible for an inflammatory reaction on body surfaces at the site of infection (usually the oral pharynx. which consists of leukocytes and numerous bacteria enmeshed in a dense network of fibrin. These enlarge and coalesce and. This exudate constitutes the characteristic diphtheritic inflammation. The umbilical cord (in diphtheria neonatorum). 3. Diphtheria is a composite of a local inflammation and a systemic intoxication. Occasionally the tracheal. and the conjunctivae are rare sites. This simultaneous damage causes hemodynamic disturbances in the organism. Fibrinous films are formed on the surface of the damaged mucous membrane. Soon small gray or white patches of exudate appear on the pharyngeal mucosa. diphtheria may occur when immunization procedures break down because of war. The lymphoid tissues both in regional lymph nodes and systemically (as in the spleen) undergo hyperplasia with the development of prominent germinal centers that are often centrally necrotic. cutaneous trauma or burns may be the site of diphtheria. Exotoxin affects cardiovascular.175 BACTERIAL INFECTIONS OF CHILDHOOD Diphtheria (D) Diphtheria is an acute infectious disease characterized by fibrinous inflammation in the focus of primary fixation of the causative agent and general intoxication due to exotoxin absorption. Less commonly. Even in medically advanced countries. Transmission to nonimmune individuals usually occurs by the respiratory route. which is passed from person to person via aerosols or traumatic skin.

3.176  In the early stages. Necrotic nephrosis and massive necroses of the cortical layer in the severe cases of toxic diphtheria are observed in the kidneys. phlegmon. . A nonspecific. propagation of the process in the small branches of the bronchial tree is called descending croup. Scarlet fever (SF) Scarlet fever is one of the forms of streptococcal infection.  Late paralysis of the heart may lead to acute cardiac failure. degeneration and necrosis of the cells are observed in the medullary layer of the adrenal glands. diaphragmatic nerve.Early cardioplegia in myocarditis and late cardioplegia or paralysis of the diaphragm due to parenchymatous neuritis when antitoxic serum is not administered in time.Intubation or tracheotomy. the local process may produce mechanical respiratory obstruction.  Toxic effects are manifested in degeneration or even destruction of myelin membrane. . and even asphyxia. cloudy swelling of myocardial fibers. hepatocytes exhibit cloudy swelling and less commonly focal necrosis. but it can also be observed in the adults. diaphragm.  If myocarditis develops at the beginning of the 2nd week of the disease and the death is caused by acute cardiac failure and an arrhythmia.  Paralysis of the voluntary muscles of the palate may produce a peculiar nasal quality of the voice and a tendency to regurgitate fluids through the nose. The epithelial surface becomes necrotic and easily adherent to the overlying membrane. which may be accompanied by development of focal pneumonia. the condition is called early cardioplegia. Diphtheria in the respiratory tract      Diphtheria of the respiratory tract is characterised by croupous inflammation of the larynx.Asphyxia (spasm of the larynx in true croup or occlusion of the respiratory tract with fibrinous films) or by accompanying pneumonia and purulent complications. . Axis cylinders undergo swelling and rarely necrosis. Neuropathic manifestations of diphtheria are usually temporary and disappear within 2 or 3 months if the patient survives.  Involvement of extraocular muscles may produce diplopia. interstitial edema. The liver is characteristically enlarged. and purulent mediastinitis. which can result in decubitus. and heart develops. trachea. points are exposed when the membrane is forcibly removed. Due to diphtheritic myocarditis the cardiosclerosis and congestive heart failure develop. Complications in diphtheria of the respiratory tract are caused by . Croupous inflammation of the larynx in diphtheria is called true croup. vagus. and bronchi with formation of fibrinous films. . 5.  Paralysis of the diaphragm may lead to aspiration pneumonia. Death is caused by . sympatic nerves). If particularly extensive. The changes of cardiomyocytes are characterized by fat degeneration and small foci of myolysis. The renal lesion usually resolves completely in patients who recover. Acute adrenal insufficiency may develop.Secondary infection in decubitus causes purulent perichondritis of the cartilages of the larynx.  Clinically apparent weakness or paralysis of limbs is rare. Hemorrhages. this adherence explains why raw bleeding. 4. it is an acute infectious disease accompanied by local inflammatory changes mainly in the pharynx and typical generalized rash.  Parenchymatous neuritis with dvelopment of the late paralysis of the palate.Asphyxia due to obstruction of fibrinous films. and the accumulation of fine cytoplasmic granules of lipid are seen microscopically. and involvement of the ciliary body may result in defective visual accommodation. Diphtherial toxin has a special affinity for peripheral nerves (often in glossopharyngeal nerve. nonsuppurative interstitial nephritis is frequent in diphtheria and is believed to be responsible for the proteinuria often observed. foci of necrosis and disappearance of lipids are seen in the cortical layer. which can be discharged at cough. stridor. The paralytic effects of diphtheritic neuropathy are often sharply localized. The disease is common in children (3-12 years old). 2.

The patients are infected by inhalation (air-droplets rout). seldom-genital tract). cervical adenitis. there is a characteristic acute. thus little of the characteristic skin reaction is evident at autopsy. microbial invasion and allergic reactions. vomiting. Microscopically. The second period (allergic). skin. serous arthritis. Rejection of the necrotic masses results in ulcers. with foci of necrosis and marked myeloid infiltration. a diagnosis of throat infection caused by S. but the disease can also be transmitted through personal belongings and foodstuffs (mainly milk). vasculitis. in other words.177 Etiology and pathogenesis       The causative agent is beta-hemolytic streptococcal group A of different serological types. The diagnosis cannot be positively made until the second stage of the disease. make up the cardinal prodromal symptoms of scarlet fever. acute suppurative mastoiditis. bacteriologic studies do not provide a means for early diagnosis. Cervical lymphatic nodes are plethoric. neutrophilic inflammatory reaction surrounding the affected tissues (skin and lymph nodes). phlegmon of the neck. This is called “primary scarlatinic affect” and “primary scarlatinic complex”. The face is also involved.  Microscopically. Because there is no specific strain of beta-hemolytic streptococci responsible for scarlet fever. General changes. 3.      The second period may develop on the 3rd . Morphology 1. there is a characteristic acute. Toxic period (1-2 weeks). auditory tube (Eustaphian tube). it can pass from the lymphatic nodes to the subcutaneous fat of the neck. and retropharyngeal abscess. enlarged. but usually a small area about the mouth (nasolabial triangle) remains relatively unaffected.5th week of the disease rarely.  Necrotic tonsillitis is characterized by coagulative necrosis and ulceration. The duration of the disease is divided into two periods. pharynx. Local changes appear the inflammatory process in the site of the primary fixation (tonsils. This hyperemia blanches on pressure and disappears on death. In the early stages there is rather severe pharyngitis and tonsillitis. the tongue becomes beefy red and glistening.  The inflammatory involvement of the epidermis is usually followed by hyperkeratosis of the skin.  Catarrhal tonsillitis (during the first few days) is manifested by hyperemia of pharynx (“flaring pharynx” or “burning faucet”) with involvement to oral cavity and tongue. toxic (first) and infectious allergic (second) ones. Skin rash. Pathogenesis of scarlet fever is complicated and explained by third factors: erythrogenic toxin. These. which is reached 1 to 5 days after the onset. juicy. sinusitis. edematous. . The most significant is development of acute or chronic glomerulonephritis with possible nephrosclerosis development.  The general changes depending on toxemia are first of all rash. The hyperemia and resultant red coloration of skin are manifestations of toxic injury (atony and dilatation) of vascular endothelium. to produce a circumoral pallor. which accounts for the scaling during defervescence. edematous. When peeling occurs. which is accompanied by regional lymphangitis and lymphadenitis. Complications are divisible into three major categories: 1 The results of bacterial disseminations locally – otitis media. neutrophilic inflammatory reaction within the affected tissues. pyogenes is not a diagnosis of scarlet fever. It presents a “strawberry” appearance because of the erythematous papillae that project from a gray-coated background. “Primary scarlatinic affect” is characterized by catarrhal or necrotic tonsillitis. middle ear. Necrosis may involve the soft palate.  A punctate erythematous rash that is most abundant over the trunk and inner aspects of the arms and legs manifests exanthema. combined with fever. Incubation period is 3-7 days. verrucous endocarditis can be observed. lungs. and headache. The second period begins with moderate catarrhal tonsillitis.

Morphology Meningococcal nasopharyngitis   It is characterized by catarrhal inflammation of the mucosa with marked hyperemia. The manifestation of extraordinary reactions to toxins (this may be brought about by hypersensitivity) – interstitial nephritis or myocarditis. Infectious M. The meningeal vessels are enlarged and stand prominently. Later the cause of death is meningoencephalitis. and glomerulonephritis. Bacteriologic investigation is necessary for diagnose. Bacteriemia and endotoxinemia lead to endotoxic shock with the development of syndrome of disseminated intravascular coagulation. fungi. Meningococcal infection is an acute infectious process which has three main forms: nasopharyngitis. and neck stiffness. The death may occur from the brain swelling with wedging of the cerebellum tonsils to the great foramen and strangulation of the oblong brain during the acute period. The causative agent is meningococcus (Neisseria meningitidis). which discharges the endotoxin. clouding of consciousness. subdural effusion caused by fluid leading into the subdural space through defects in the arachnoid and occuring most commonly in children. By the end of the 2nd . . and cranial nerve palsies probably related to inflammatory involvement of nerve roots crossing the subarachnoid space. The process begins with basal surface and passes through. and chronic (bacterial or fungal).178  2 The result of bacterial dissemination generally – metastatic foci of infection throughout the body. can be broadly classified as acute pyogenic (usually bacterial). purulent. 3. purulent ependymitis or general cerebral cachexia due to hydrocephalia and atrophy of the brain hemispheres during the following periods. Etiology. green-yellow. irritability. The purulent process involves the meninges of the spine. nonsuppurative arthritis. By the 5th -6th day it becomes denser due to fibrinous effusion.3rd day the exudate becomes thicker. photophobia. edema of the posterior wall of the pharynx and hyperplasia of lymphatic follicles. This form is of great epidemiological importance as clinical diagnosis is often difficult. or parasites. Meningococcal meningitis          It is characterized by the hyperemia of the pia mater. Meningitis (M)        Meningitis (leptomeningitis) is an acute or chronic inflammatory process chiefly affecting the pia and arachnoid mater. purulent meningitis and meningococcemia. The infection may extend into the ventricular system through the foramina of Magende and Luschka causing ventriculitis. pericarditis. The death is caused by toxemia or septic complications. but the disease may occur in persons of any age. cerebrospinal fluid (CSF) and may be caused by bacteria. the disease is more common in children under 5 years. aseptic (usually viral). saturated with dull serous exudate during the first days of the disease. Meningococcemia   Duration is 24-48 hours. The typical patient with acute pyogenic meningitis has general signs of infection with the added symptoms and signs of meningeal irritation: headache. the perivenous spaces to the convex surface mainly of anterior portion of the brain. but chemical meningitis may also occur in response to a nonbacterial irritant introduced into the subarachnoid space. locating there in the form of a yellow-green “cap”. This is characterized by periodic epidemics. or trunk septicemia. It is usually caused by an infection. Other complications of meningitis include hydrocephalus resulting from ventricular obstruction or meningeal fibrosis.

acute renal insufficiency is not so common (in the adults). There may be vesicles or dull dryish foci of necrosis in the centre of the skin elements. Changes in the serous layers of the pericardium are observed. the death occurs from septicemia or purulent meningitis. . changes in the joints. Focal necroses and hemorrhages or bilateral massive hemorrhages with the development of acute adrenal insufficiency (Waterhouse-Friderichsen syndrome) are noted in the adrenals. star-like. lower extremities. Necrosis of nephrothelium of the tubules (necrotic nephrosis) is observed in the kidneys. The changes of the microcirculation are characterized by vasculitis and necrosis. its severity is aggravated by hemorrhages to the adrenals. The death of the patients is caused by bacterial shock. skin rash.179        Changes on the organs are characterized by generalized damage of microcirculation. Purulent arthritis is observed in the small joints of the extremities. Serous meningitis and hemorrhage may occur. eyelids and scleras. located mainly on the buttocks. The rash is hemorrhagic. When the duration of the disease is prolonged. vascular membrane of the eyes. adrenal glands and kidneys.

fibrin deposition. intestinal phlegmon. coli enterotoxin.  Lymphadenitis develops in the regional lymphatic nodes. boydii. Symptoms appear 2 to 5 days after the ingestion of bacteria. Water and electrolyte balance must be maintained to prevent dehydration. like cholera toxin and E. neutrophilic reaction accompanied by congestion. comprises the characteristic dysenteric stool of shigellosis. amyloidosis. The epithelium persists only in the depths of the crypts. . pyelonephritis.  Complications of dysentery are . Transmission occurs by the fecal-oral route. flexneri. The dose of organisms and the status of host defenses influence the incubation period and severity.Extraintestinal complications are bronchopneumonia. which is related antigenically to the enterotoxin of enteropathogenic E. activates membrane-associated adenyl cyclase. Fibrinous colitis. 4. and cachexia. sonnei as well as certain O-type enterotoxic E. . necrosis of renal tubular epithelium. suppurative. and goblet cells contain no mucus in the acute stage. The key to the pathogenicity of Shigella is its ability to invade and multiply in the epithelium and lamina propria of the terminal ileum and colon. neutrophils. Amebiasis The protozoan parasite Entamoeba histolytica infects approximately 500 million persons in developing countries. prostration. coli. and erythrocytes. and impaired mental status. Bacillary D. intestinal pain. Ulcer formation (ulcerative colitis). When the disease remits. Epithelial regeneration is rapid and healing is complete in 2 weeks. then diffusely covers the mucosa and produces a dirty gray-to-yellow pseudomembrane. fibrin. induces hypersecretion of fluid and electrolytes from the mucosa of the terminal ileum. While clearly secondary to invasion. S. and is covered by pus and mucus.180 GASTROINTESTINAL INFECTIONS Shigella bacillary dysentery (D)         Dysentery refers to diarrhea with abdominal cramping and tenesmus in which loose stools contain blood. lyses colonic epithelial cells. S.coli. intoxication. The mucosa becomes edematous and hyperemic. Sloughed pseudomembrane. 3. Amebae cause dysentery – bloody diarrhea. pus.  Histologically. small-focal necroses in the liver. but the role of enterotoxin produced by some species of Shigella in the pathogenesis of dysentery is uncertain.Scar stenosis of the intestine is less common.  The death may cause by intestinal or extraintestinal complications.Perforation (microperforation) of the ulcer with development of. The disease is common in India. and thromboses of small vessels. and mucus. shiga toxin. and Colombia. paraproctitis or peritonitis. . and the ulcers heal by regeneration of the mucosal epithelium. Healing of the wound. this granulation tissue fills the defect. and destroy host cells. Mexico. 2. is caused by Shigella dysenteriae. As the disease progresses. Common changes are spleen hyperplasia. Morphology Colitis has 4 stages: 1. consisting of necrotic mucosa. and pylephlebilic abscesses of the liver. marked edema. and invade the bowel well. they enlarge and protrude over the surface of the mucous membrane (follicular colitis and follicular-ulcerative colitis). there is predominantly mononuclear leukocytic infiltrate within the lamina propria. fatty degeneration in the heart and liver. Shiga toxin probably contributes to the profuse diarrhea that precedes dysentery in some patients. serous (toxic) arthritis. together with blood-tinged mucus. a fibrinosuppurative exudate first patchily. Endotoxin probably adds to necrosis. and S. but the surfaces of the ulcers are covered with an acute. Within the course of 24 hours.  In case of solitary follicle cell hyperplasia. the ulcer margins are transformed into active granulation tissue. fever – when they attach to the colonic epithelium. Thus. This enterotoxin.Intraintestinal hemorrhage . Catarrhal colitis.

All this occurs in the incubation period. Amebic liver abscesses are treated with drainage and drugs or with drugs alone Rarely. The condition results in necrosis of the intestine lymphatic system. rectum. Bacteremia is associated with generalization of the infection. The earliest amebic lesions show neutrophilic infiltrates in the mucosa.181 Morphology      Amebiasis most frequently involves the cecum and ascending colon. burrow through the tunica propria. Bacteremia is also associated with elimination the causative agent that is excreted with the sweat. Amebic liver abscesses have a scant inflammatory reaction at their margins and a shaggy fibrin lining. Morphology The changes in typhoid fever can be local and generalized. Typhoid fever   Typhoid fever (enteric fever) is an acute intestinal infectious disease caused by Salmonella typhy abdominalis. and bile. the abscesses are sometimes filled with a chocolate-colored. whence they reach the liver and then. Bacteremia develops (1st week of the disease). Because of hemorrhage into the cavities. Salmonellas invade nonphagocytotic interstitial epithelial cells as well as tissue macrophages. On penetrating the intestinal mucosa. Epidemics are possible but at present the disease is rare. the overlying surface mucosa is deprived of its blood supply and sloughs. In severe. and are halted by the muscularis mucosae. discrete abscesses. Pathogenesis        The bacteria multiply in the lower portion of the small intestine and produce endotoxins. and appendix. quickly enter lymphatic vessels and mesenteric nodes. milk. urine. Amebae invade the crypts of the colonic glands. the bloodstream. Secondary bacterial infection may make these abscesses purulent. or less often multiple. urine. which later develop into ulcers that contain few host inflammatory cells and areas of extensive liquefactive necrosis. pasty material likened to anchovy paste. Beginning with the 2nd week antibodies to the causative agent are determined in the blood with agglutination reaction (Widal’s reaction). The infection is parenteral. the entire colon is involved. sweat) contain the microbes. by the thoracic duct. The most favourable conditions for the life of the bacteria are in the bile where they intensively multiply (bacteriocholia). followed in order by sigmoid. the bacillus can be isolated from the blood (homoculture). some exceeding 10 cm in diameter. its course is not severe. gram-negative bacteria that cause a self-limited and waterborne gastroenteritis or a little-threatening systemic illness marked by fever. As the amebic abscesses enlarge. the organisms enter Peyer’s patches and solitary follicles. they produce pain by pressing on the liver capsule and can be visualized with ultrasound. amebic abscesses reach the lung and the heart by direct extension or appeared through the blood into the kidneys and brain. The mucosa between ulcers is often normal or midly inflamed. however. full-blown cases. They are excreted with the bile to the small intestine and cause hyperergic reaction in the previously sensibilized lymphatic follicles. parasites penetrate portal vessels and embolize to the liver to produce solitary. The source of infection is a sick person or a human carrier whose excretions (faeces. usually 10 to 14 days. faeces. As the lesion progresses. This is the first stage of the disease. In about 40% of patients with amebic dysentery. The patient is especially infective during this period. . odorless. in which generalization of the infection occurs before localizing lesions draw attention to the intestine. Salmonellosis and typhoid fever   Salmonellae are flagellated.

lymphocytes and plasma cells. Medullar swelling is acute proliferative granulematous inflammation in lymphoid apparatus of intestine with development macrophagal granulomas (“typhoid granuloma”). Salmonellosis      Salmonellosis is an intestinal infection caused by salmonellas. soft. called “typhoid nodule”. The death is caused by the complications. which may be associated with gallstones. After 7 to 10 days. containing bacteria.  The latter are the processes in the organs of the lymphatic system and degenerative changes in the parenchymal organs. Peyer‟s patches in the terminal ileum become sharply delineated. In mucosa the catarrhal inflammation is found out. Clinical symptoms are accompanied with endotoxin and endotoxinemia: fever. The disease resembles cholera that is why it is called “home cholera”. The most prominent changes develop in the Peyer's patches of the ileum (ileotyphus). diarrhea and hypotony and endotoxic shock. Healing (recovery). and prominent sinus histiocytosis and reticuloendothelial proliferation. osteomyelitis. Complications    Intestinal (intraintestinal hemorrhages. ulcer perforation. the picture in the intestine is complicated by necrosis and ulceration of areas that formerly exhibited lymphoid hyperplasia. Edges of ulcer are irregular with necrotic tissue. 2. obliterated follicular markings. Pathology. It is anthropozoonosis and occurs both in human beings and animals. septic.  The spleen is enlarged. with enlargement of draining mesenteric lymph nodes. plateau-like elevations up to 1 cm in diameter.  These distinctive nodules also occur in the bone marrow and lymph nodes. 2. Extraintestinal (pneumonia. Incubation’s period is 12-36 hours. intramuscular abscesses). randomly scattered foci of parenchymal necrosis in which the hepatocytes are replaced by a phagocytic mononuclear cell aggregates. Proliferation of phagocytes with enlargement of reticuloendothelial and lymphoid tissues throughout the body develop. whereas neutrophils are present near the ulcerated surface. purulent perichondritis of the larynx. Typhoid salmonellosis (specific enteric fevers) resembles typhoid fever. The changes in typhoid fever may be typical only for this disease as well as characteristic for any infection. Ulcer formation (“unclear ulcers”). typhoid. Septic salmonellosis (septicemic diseases without specific organ-system localization) differs from interstitial one in hematogenic generalization of the causative agent with formation of metastatic abscesses in different organs while the changes in the small intestine are not significantly pronounced. In this stage the perphoration can develop. necroses undergo to petrification. 4. peritonitis). 3. and bulging. ulcers are smaller and punctate. Zenker‟ s necrosis of the abdominal muscles.  Roseolar-papular rash and typhoid granuloma in different organs occurs.  The liver shows small. resulting in oval ulcers with their long axes in the direction of bowel flow. corresponding to the smaller lymphoid follicles there. 3. Each stage takes approximately one week. cholangiotyphus. 5. “Clean ulcer” has regular shape without necrotic tissue. 1. 1. Follicles are protruded in intestine lumen. Granulomas are sclerosed. General changes. It is characterized by acute gastroenteritis causing severe-dehydration of the organism. In the colon.  Gallbladder colonization. Their surface is striated and like brain. causes a chronic carrier that may require cholecystectomy to eliminate bacterial shedding. salmonella enteritidis. They consist of large macrophages with pail-pink cytoplasm. Macrophages. Salmonellas cause three types of human disease (salmonellosis): interstitial (toxic). salmonella cholera suis. the mucosa over the swollen lymphoid tissue is shed. with uniformly pale red pulp.  Atypical forms are pneumotyphus. The most often pathogenic organism is Salmonella typhi murium. Necrosis. Interstitial salmonellosis (gastroenteritis) develops in food poisoning. These changes develop in 5 stages.182 Local changes occur in the mucous membrane and lymphatic system (group and solitary follicles of the intestine). In the second week. .

myocardium. Bile formation is disturbed. gallbladder. the muscles become dark red.  Rigor mortis develops quickly and persists for several days. with death or recovery occurring within a few days. Vibrios traverse the stomach. creasy (especially on the fingers. and pulp hemosiderosis is observed. brain) can be. The only significant natural reservoir of cholera appears to be humans. resulting in severe diarrhea and hypovolemic shok. body temperature may be subnormal. After the onset of diarrhea. The vibrios never invade the enteric epithelium but instead remain within the lumen and secrete their endotoxin. cholera and food prepared with contaminated water is infectious. An asymptomatic convalescent carrier state is uncommon but can occur. The hematocrit may rise to 55-65 and the plasma specific gravity to 1. The outlines of the muscles are well pronounced (“gladiator posture”). lethargy. The gallbladder is not distended. hypovolemic shock.  The skin is dry. after which a profuse watery diarrhea occurs usually without tenesmus or abdominal distress.  The spleen diminishes. and the only clinically significant portal of entry is the alimentary tract by the fecal-oral route. cholera are appreciably sensitive to normal gastric acidity. gram-negative bacteria that have been caused of seven great long-lasting epidemics (pandemics) of diarrheal disease. and metabolic acidosis follow quickly. which evokes an intense outpouring of watery fluid and electrolytes into the gut lumen. Choleric gastroenteritis is characterized by the hard diarrhea and vomit. 3. Prostration is therefore rapid and profound. serous edema of the intestine mucosa. hemoconcentration. but renal function improves when . sunken eyes. The serous membranes are also dry. its capsule becomes creasy. and elevation of serum proteins. subcutaneous fat and muscles are dry. Choleric exicosis (algid):  Acute dehydration. Drinking water contaminated with V. a weak pulse. Patients are usually a febrile. This is due to the exotoxin of the Vibrio cholera. Choleric enteritis is characterized by the hard diarrhea.  The patient exhibits dry skin. dysbacteriosis when the treatment is inadequate. Due to rapid development of rigor mortis. The disease is ordinarily self-limited. which is nearly identical to E. purulent complications. called “rice-water stool”. enter the small intestine and propagate. Secretory diarrhea is caused by released of an endotoxin. resembles “goose’s skin”. which is stretched out in the form of threads. urine production ceases. and under such circumstances most patients survive. cyanosis. Those with a normal gastric acidity are much less susceptible than those with low levels of stomach acid as a result of a gastrectomy or other cause.  Changes in different organs due to dehydration (spleen. the follicles are atrophic. Cholera           Cholera is an acute gastrointestinal infectious quarantinic disease and is characterized by diarrhea and exicosis. Fluid loss can exceed 10 liters per day.  Degeneration and focal necroses in the liver develop. Fluid loss may exceed 1 liter per hour. The loss of sodium and water causes severe diarrhea.coli endotoxin. Vibrio cholera locates in water often. faint heart sounds.  Necrotic nephrosis of the main portions of nephron (the changes observed in oliguria and acute renal failure) is noted in the kidneys. covered with sticky transparent mucus. called cholera toxin. V. kidneys. dark. Toxicoinfectious shock.  There are degenerative and necrobiotic changes in the brain and myocardium. Clinical-morphological stages of cholera 1.  The mucous membranes. Vibrio cholera is comma-shaped. “beef-steak hands”). filled with clear light bile (“white bile”). The blood in the veins is thick.  Treatment is prompt rehydration.183  Complications.050. The incubation period is usually 1 to 5 days. 2. Morphologically: swelling of enterocytes. increase of dehydration. liver.035-1.

coli appear to be the cause of this bronchopneumonia. and enteroadherent. Enteroadhesiveness is plasmid-dependent and is apparently mediated by pili. Enteroinvasive E. although in bacteremic patients pneumonia may result from seeding by septic emboli. and functionally related to the cholera toxin. Enterotoxigenic E. coma. although the toxin of E. Dehydration and electrolyte imbalance is a significant cause of morbidity and mortality when appropriate rehydration is lacking . ranging from mild cystitis to fatal pyelonephritis. uremia. coli invades the intestinal mucosa and causes local tissue destruction and sloughing of necrotic mucosa. leads to prolonged renal failure. The heat-stable toxin of E. coli causes a diarrheal disease by elaborating two plasmid-mediated enterotoxins. most often in elderly patients with underlying chronic disease. pneumonia. Enteroadhesive E. coli produces a dysentery-like disease resembling shigellosis. At present owing to early adequate treatment (administration of water and salts.184 fluid and electrolytes are replaced. which bind tightly to receptors on the intestinal epithelial cells. Inadequate replacement. coli meningitis die. and the survivors frequently suffer from neurologic or developmental anomalies. Complications There are nonspecific and unspecific complications of cholera. Enteroinvasive E. but it is a major cause of neonatal meningitis. coli is the etiologic agent in many cases of nosocomial pneumonia. with acute damage of tubules and the vacuolar lesions of hypokalemia. In addition. especially in patients with disease lasting more than a week. and intoxication. phlegmon. although it is less severe and requires a much larger infecting dose of organisms. E. . The heat-labile toxin is antigenically. Between 40% and 80% of infants with E. coli causes at least three patterns of human enteric diseases: enterotoxigenic. structurally. 1. Nonspecific complications are pneumonia. coli is also responsible for 50% of traveller's diarrhea. is also an important opportunistic pathogen. and neonatal meningitis. coli cause meningitis in adults. As in cholera. E. Enterotoxigenic E. abscesses. Empyema is a common complication. and sepsis. antibiotics) the death rate has been considerably decreased. enteroinvasive. however. 3.a common combination among infants in less developed countries. are caused by E. a gram-negative bacillus that is part of the intestinal flora. Cholera typhoid and postcholera uremia are specific complications. coli is different from cholera toxin and apparently acts to impair sodium and chloride absorption and to reduce the motility of the small intestine. 2. Only rarely does E. coli is less potent than that of cholera. urinary tract infections. About 80% of all infections of the urinary tract in humans. coli has only recently been associated with diarrheal diseases. The mechanism of diarrhea is unknown. coli. Aspirates of endogenous oral flora containing E. erysipelas. the resulting activation of adenylcyclase produces a hypersecretory diarrhea. The death occurs in algid period and is caused by dehydration. causing diarrhea and dysentery. Bloody mucoid stools contain neutrophils. Escherichia coli Infection Escherichia coli.

Tissue reaction to tubercle bacilli is different in healthy organism not previously infected (primary infection) from an organism who is previously infected (secondary infection). the site of inoculation is indurated and dark. The skin lesion ulcerates which . plays a major role in the development of lesions in tuberculosis.  Infected sputum into larynx (tuberculous laryngitis). This takes place by macrophages carrying the bacilli into the surrounding tissues. This process is a manifestation of delayed type of hypersensitivity and is comparable to primary tuberculosis in children. Latin America and Asia. 2.185 TUBERCULOSIS     Tuberculosis is a chronic communicable disease with specific granulomatous inflammation caused by a variety of tubercle bacilli. This occurs either as a result of tuberculous bacillemia because of the drainage of lymphatics into the venous system or due to caseous material escaping through ulcerated wall of a vein. t. Other factors contributing to higher incidence of tuberculosis are malnutrition. The characteristic lesion is a specifical granuloma with central caseous necrosis. a nodule develops at the inoculation site. poverty. The organism is a strict aerobe and thrives best in tissues with high oxygen tension like in the apex of the lung. especially Micobacterium tuberculosis hominis and M. Through ingestion into GI tract leads to development to tonsillar or intestinal tuberculosis. inadequate medical care. The lungs are the prime target. more common in poorer countries of Africa. Local spread.  Transplacental route results in development of congenital tuberculosis in fetus from infected mother and is a rare mode of transmission. liver. skin. Through mucous membranes of mouth and throat. crowding. Hypersensitivity and immunity in tuberculosis    Hypersensitivity or allergy. 2.  Renal lesions into ureter and down to trigone of bladder. After this period. Lymphatic spread. Primary complex is primary focus with lymphangitis and lymphadenitis. Ingestion.  Transbronchial spread into the adjacent lung segments. the tubercle bacilli are injected into the skin who has been infected with tuberculosis 4-6 weeks earlier. Tuberculosis still continues to be worldwide in distribution. bones and other tissues and is known as miliary tuberculosis. In 1 -2 days. bovis. By the natural passages. but any organ may be infected. 1. alcoholism and immunocompromised states like AIDS. Infection may spread from:  Lung lesions into pleura (tuberculous pleurisy). which subsequently ulcerates and heals poorly. Hematogenous spread. Tuberculosis is primarily an infection of lymphoid tissues. and immunity or resistance.  Swallowing of infected sputum (ileocecal tuberculosis). Tissue changes seen in tuberculosis are not the result of any exotoxin or endotoxin but are instead the result of host response to the organism.   Spread of tuberculosis 1. In the primary infection. intradermal injection of tubercle bacilli into the skin evokes no visible reaction for 10-14 days. chronic debilitating conditions like uncontrolled diabetes. 3. which is in the form of development of cell-mediated hypersensitivity (or type IV hypersensitivity) and immunity. Mode of transmission Human beings acquire infection with tubercle bacilli by one of the following routes: By inhalation into the respiratory tract. This produces millet seed-sized lesions in different organs of the body like lungs. 4. In the secondary infection.  Inoculation. attaining a diameter of about 1 cm.  Tuberculous salpingitis into peritoneal cavity (tuberculous peritonitis). kidneys.

Cell-mediated immunity with consequent delayed hypersensitivity reaction develops with healing of the lesion. but the cell-mediated immunity persists. are as under: The inhaled organism enters the alveolus and is ingested by the alveolar macrophage. The giant cells may have 20 or more nuclei. or they may be present centrally (foreign body giant cells). The macrophages continue to enter the tissue either from circulating monocytes or from local proliferation.these modified macrophages resemble epithelial cells and are called epithelioid cells. some viral infections.186    heals quickly and the regional lymph nodes are not affected. calcium salts may get deposited in the caseous material (dystrophic calcification) and sometimes the lesion may even get ossified over the years. The giant cells may be Langhans’ type or they may be foreign body type. However. In 2-3 days. These nuclei may be arranged at the periphery like horseshoe or ring or clustered at the two poles. Hodgkin’s disease and fulminant tuberculosis. the macrophages undergo structural changes as a result of immune mechanisms . Bacilli Calmette Guerin (BCG). . This is called Koch’s phenomenon and is indicative of hypersensitivity and immunity in the host. Post primary tuberculosis a) Secondary tuberculosis b) Hematogenous tuberculosis Primary Tuberculosis  The infection of an individual who has pot been previously infected or immunised is called primary tuberculosis or Ghon‟s complex or childhood tuberculosis. This stage is called soft tubercle.1 ml of tuberculoprotein. rendering the host tuberculin-positive and hence immune. which is the hallmark of tuberculous lesions. Some of the macrophages form multinucleated giant cells by fusion of adjacent cells. purified protein derivative (PPD). Release of cytokines in response to sensitised CD 4 + T cells and some constituents of mycobacterial cell wall play a role in formation of granuloma. Evolution of tubercule           The sequences of events. Primary tuberculosis II. its growth inhibited or multiplies inside the macrophage. tuberculosis can either be killed by the macrophage. Acid-fast bacilli are difficult to find in these lesions and may be demonstrated at the margins of recent necrotic foci and in the walls of the cavities. The macrophages start phagocytosing the tubercle bacilli. The M. Around the mass of epithelioid cells and giant cells is a zone of lymphocytes. Hypersensitivity and immunity are closely related and are initiated through T lymphocytes sensitised against specific antigens in tuberculin. Immunisation against tuberculosis. which take place when tubercle bacilli are introduced into the tissue. Protective immunisation against tuberculosis is induced by injection of attenuated strains of bovine type of tubercle bacilli. The lesion at this stage is called hard tubercle due to absence of central necrosis. the centre of the cellular mass begins to undergo caseation necrosis. Types of tuberculosis I. In granuloma enclosed by fibrous tissue. A positive test is indicative of cell-mediated hypersensitivity to tubercular antigens but does not distinguish between infection and disease. Tuberculin (Mantoux) skin test. plasma cells and fibroblasts. It behaves more like a parasite and lives in symbiosis with the cell. Within 10-14 days. The test may be false positive in atypical mycobacterial infection and false negative in sarcoidosis. This test is done by intradermal injection of 0. patients having disseminated tuberculosis may show negative test due to release of large amount of tuberculoproteins. Delayed type of hypersensitivity develops in individuals who are having or have been previously infected with tuberculous infection which is identified as an indurated area of more than 15 mm in 72 hours.

and calcification. The caseous material can enter into a bronchus and then spread to other parts of the lung or the opposite lung. In over 90% of normal adults the infection follows this self-limited course. The enlarged and caseous mesenteric Iymphnodes may rupture into peritoneal cavity and cause tuberculous peritonitis. erodes the bronchial tree. but a few remain viable for years. Pulmonary component (Primary affect or primary focus or Ghon‟s focus) is 1-2 cm solitary area of tuberculous pneumonia surrounding by perifocal serous inflammation. When this happens the caseous material is discharged leaving an acute cavity. The lymphatics draining the lung lesion contain phagocytes containing bacilli and may develop beaded. Heal by fibrosis and in time undergo calcification and even ossification. the affected lung may become bronchiectactic. such as: paratracheal.9. resulting in a tuberculous bronchopneumonia.10 segments usually. This consists of enlarged hilar and tracheo-bronchial lymph nodes in the area drained. This leads to a variety of clinical symptoms and pathological changes and form the spectrum of progressive primary tuberculosis. 1. If the collapse persists for a long time. fibrous scarring. Primary complex or Ghon’s complex in lungs consists of 3 components: 1. with compensatory emphysema or an obstructive emphvsema. The initial infection produces only slight abnormalities and may cause only slight malaise and mild fever. In the case of primary tuberculosis of alimentary tract due to ingestion of tubercle bacilli. Fate of primary Tuberculosis Primary complex may have one of the following sequelae: I. cervical and development of tuberculous mezadenitis. II.187      Primary complex or Ghon’s complex is the lesion produced at the portal of entry with foci in the draining lymphatic vessels and lymph nodes. 2. in both the lung and the lymph nodes the lesions of the Ghon complex heal. the resting bacilli may break out and cause serious tuberculous infection. which can produce either a complete or partial obstruction. the primary focus in the lung continues to grow called progressive primary tuberculosis. Lymphatic vessel component.  The infected material can by a retrograde spread. Therefore. The affected lymph nodes are matted and show caseation necrosis. 2. miliary tubercles along the path of hilar lymph nodes. In some cases. The incidence of disseminated form of progressive primary tuberculosis is particularly high in immunocompromised host (in patients of AIDS). Later. supraclavicular. undergoing shrinkage. Most of the organisms die. if immune mechanisms wane or fail. It must be differentiated from lung abscess caused by other conditions.  A subpleural focus can involve the pleura and cause pleuris followed by pleural effusion. Tuberculous lymphangitis the lymphostasis and tuberculi along the edematous perivascular tissue occurs. a sequence that results in adjacent “satellite” lesions. cause bronchial lesion and result in endobronchial ulceration and stenosis. 8.  The lesion may enlarge in size and liquefy with a cavity formation (so called “primary tuberculous caverna”) as in an adult or produce an area of consolidation. The primary complex in lungs is located in the lower part of the right upper lobes or the upper part of the lower lobes in 3.  The enlargement of the bronchial lymph nodes may cause extrinsic compression on the bronchus or erode into the adjacent structures. 3. and spreads. Commonly involved tissues for primary complex are lungs and hilar lymph nodes. Lymph node component. a small primary focus is seen in the intestine with enlarged mesenteric Iymphnodes producing tabes mesenterica. because the cellular immune response is sufficient to control the multiplication of bacilli. It is located under the pleura. This may lead to a segmental collapse. in the lower part of upper lobe and has white-yellow color and firm consistence. Growth of primary parenhymal injury  The primary Ghon focus in the lung is characterized by enlargement of caseous necrosis. Lymphogenous spreading  Lymphogenous spreading is characterized by involvement the new groups of lymph nodes. subclavian. .

 Tuberculosis of the kidneys. b) Chronic miliary tuberculosis.  Tuberculosis of genital tract. Generalized hematogenous tuberculosis is more serious form with dessimenation of granuloms: а) The most acute tubercular sepsis. complete or partial obstruction. liver. Features of hematogenous-disseminative tuberculosis:       May by in adults only. The name "miliary" derives from their supposed resemblance to millet seeds. Presence of unpulmonary tubercular foci. It may be  Bone.articular. A punctate area of necrosis may be seen in the center. Hematogenous spreading The most serious immediate complication is miliary tuberculosis. spleen. tuberculosis and dissemination throughout the body. d) Chronic miliary tuberculosis.plural localization. and in high-risk racial groups. meninges. Development of the pneumosclerosis and emphysema of lungs. coxitis (hip joint disease). The bacilli lying dormant in acellular caseous material are activated and cause progressive hematogenous tuberculosis. Microscopically. yellowish white. Cor pulmonale (hypertrophy of right ventricle of heart).  Hematogenous tuberculosis is characterized by proliferative reaction or formation of the granulomas and hematogenous spreading.5 mm to 2 mm in diameter. Prevalence apex. gonitis develop. b) Acute general miliary tuberculosis. The lesions are classically 0. in alcoholics. Hematogenous tuberculosis with unpulmonary lesions or organic tuberculosis is characterized by acute and chronic destruction and insufficiency of organs. Classification of Hematogenous tuberculosis 1. . c) Acute general large-focal tuberculosis. The lymph node enlargement persists for a longer period and may cause further lymphatic or hematogenous spread. Few organs are spared. usually with a central necrotic portion in which numerous organisms are seen. Hematogenous tuberculosis appears after primary tuberculosis under following conditions:  The presence of sensibilization to tuberculin. in which there is invasion of the bloodstream by M. The enlargement of the lymph nodes may produce a wheeze by compressing the bronchus. This occurs when the parenchymal part of the Ghon complex involves a pulmonary artery or vein and discharges its infected contents into the blood. In tuberculosis of bones and cartilages tuberculous osteomyelitisespccially spondylitis. c) Chronic large-focal tuberculosis or hematogenous-disseminative. Proliferative tissue reaction. 3.  The presence of foci is healed after hematogenous generalization of primary tuberculosis (sifting). and bone marrow. Postprimary Tuberculosis Hematogenous Tuberculosis The healed lesions of primary tuberculosis may get reactivated. Miliary tuberculosis used to be found most often in young children. 2. but in industrialized countries it has become more common in the elderly and debilitated. 3. and evenly distributed through the affected organ.  Strongly pronounced immunity.188           The effect of external compression of the Iymph nodes on the bronchus is similar to what happens in the retrograde involvement from the parenchyma of the lung. Hematogenous pulmonary tuberculosis а) Acute miliary tuberculosis. those most often involved are the lung (mainly by recirculation of the organisms). the lesions of miliary tuberculosis consist of small granulomas. Multiple minute granulomas develop in many organs of the body. kidney.

Caseous pneumonia develops due to progression of infiltrative tuberculosis. the cough worsen and the sputum may be streaked with blood. Complications of cavitary secondary tuberculosis . caseous material. A tuberculoma is typically a firm. The symptoms of secondary tuberculosis begin with cough. lobulated mass of granulomatous inflammation with central caseous necrosis. 4. up to several centimeters in diameter.  Shifts of the clinical-morphological forms. but are most common in the cerebellum.the so-called coin lesions. Tuberculosis of the brain is most important hematogenous localization. During the treatment the exudative process is replaced by proliferative process. where the organisms were seeded during the primary infection. Internal surface may be to connect with bronchus. which may show foci of dystrophic calcification. 6. Fibrous-local tuberculosis forms due to intensification of acute local tuberculosis with formation of fibrous capsule. endogenous tubercle bacilli in a sensitized patient who has had previous contact with the tubercle bacillus. the disease is caused by reinfection with exogenous bacilli. the wall of cavity shows eosinophilic. Tuberculous abscess. and walled off by fibrous tissue. Lesions occur within the cerebral hemispheres. Tuberculosis of endocrine organs and others. From these cavitary nodules the organisms can spread through the lungs and be discharged into the air during bouts of coughing. acellular center. and often night sweats. 5. Foci of caseous necrosis are incapsulated and petrificated. May cause meningitis or abscess. which may be erroneously attributed to smoking or to a “cold”. The wall of cavern has three membranes:  Internal membrane occurs by necrotic tissue. Only Pulmonary localization takes place. meso--. Acute cavernous tuberculosis develops due to lyses of caseous necrosis and characterized by formation of the round cavity. fatigue. Acute local tuberculosis is characterized by specific endo-. therefore process spreads along bronchi into others sites of the lungs. The caseous material from a case of secondary tuberculosis in an individual with high degree of hypersensitivity may spread to rest of the lung producing caseous pneumonia. Tuberculoma consists of focus necrosis surrauded by fibrous capcule. granular. and panbronchitis. Infection is most marked around the base of the brain and. even when infection is treated.  Contact and intracanalicular spreading. The caseous changes prevail over perifocal inflammation.  External membrane occurs by fibrous tissue. even decades later. Widespread coalesced tuberculous granulomas composed of epithelioid cells. As the disease progresses. Low-grade fever develops. with features of chronic meningitis. 3. Treatment with antibiotics is usually ineffective and surgical excision is required. 2. Langhans‟ giant cells and peripheral mantle of lymphocytes and having central caseation necrosis are seen.  Medium membrane occurs by special granular tissue. The rupture of a branch of the pulmonary artery in the wall of a cavity leads to massive hemoptysis and asphyxiation or exsanguination. there is often development of meningeal fibrosis to cause hydrocephalus. 7. anorexia. Fibrous – cavernous tuberculosis is most frequent form. which contains numerous tubercle bacilli. The cuter wall of cavity shows fibrosis.189    Tuberculosis of skin. Meningitis is characterized by numerous granulomas in the leptomeninges. Microscopically. (tuberculoma) forms with infection of the brain parenchyma. Infiltrative tuberculosis is characterized by extension of perifocal inflammation. weight loss. It must be differentiated from tumor of the lungs. Size of tuberculoma may be near 2-5 cm.  Secondary tuberculosis may develop any time after primary infection. Secondary Tuberculosis  Secondary tuberculosis usually results from reactivation of dormant. In some cases. with general malaise. A fibrous capsule surrounds a caseous.  Reactivation typically begins in the apical or posterior segments (often 1-st and 2-nd segments) of one or both upper lobes (“Simon’s foci”). Macroscopically. Forms or stages of the secondary tuberculosis 1. the lesions are spherical and cavitary . It must be differentiated from primary cavernous tuberculosis.

Extension to pleura producing bronchopleural fistula. and shortness of breath. Thickened pleura from adhesions of parietal pleura. Scarring and calcification. . Implantation of bacilli in the larynx. pleural fibrosis and adhesions. bronchi. Pneumothorax.Cirrhotic tuberculosis is a progressive variant of fibrous – cavernous tuberculosis. and pain on swallowing. Erosion into a bronchus. and trachea. 6. which causes laryngitis. These pulmonary lesions of secondary tuberculosis are often complicated by a variety of secondary effects. sharp pleuritic pain. with associated pleurisy. Chronic renal insufficiency due to development of amiloidosis of kidneys. 5. which seeds the mucosal lining of bronchioles. bovis) can lead to entrapment of bacilli in lymphoid patches of small and large bowel. which spills bacilli into the pleural cavity. hoarseness. Acute hemorrhage due to arrosion of vessels. Tuberculous empyema from deposition of caseous material on the pleural surface. Causes of death     Chronic respiratory-cardiac insufficiency due to development cor pulmonale. 2. Lesions of secondary tuberculosis acquired through the gastrointestinal tract (usually with M. Spread to other areas.190     Aneurysms of patent arteries crossing the cavity producing hemoptysis. Lungs are deformed due to development of the diffuse pneumosclerosis. including 1. 3. t. Due to intoxication and sepsis. 8. Rupture of a caseous lesion. 4.

chiefly plasma cells. Syphilitic aortitis. plasma cells and macrophages with mild arteritis. which may affect large parts of any organ or tissue but particularly bones. the gummas contain a center of coagulated. termed hepar lobatum because of the simulation by the deep scars of multiple lobes. with scattered macrophages and lymphocytes and an obliterative endarteritis. The aorta is affected by an infiltration of lymphocytes and plasma cells beginning around the vasa vasorum and extending into the media.  This is a localized area of necrosis. The lesions. shallow ulcer. The essential pathology is the presence of very numerous spirochaetes accompanied by focal infiltration of lymphocytes. Infectivity is very high. Tissue destruction is minimal and healing occurs without scarring. There is compensatory irregular thickening of the intima (tree-bark appearance). .  Testicular gummas often cause painless enlargement of the affected testis. This stage is characterized mainly by local destructive lesions.  In the liver. the chancre is a slightly elevated.  Bone and joint gummas lead to areas of cortical and articular destruction. ulceration of mucous membranes. It occurs years after the initial infection and most frequently involves the aorta. up to several centimeters in diameter that erodes to create a clean-based. It presents as a widespread skin rash (pox) of varying appearance. 3. plasma cell-rich infiltrates. 2. firm. designated meningovascular Syphilis. causing weakening due to focal destruction (windowing) of the specialized elastic tissues. testis and liver and looks like white-gray and rubbery formation. Secondary Syphilis. which may occur at any time for many years after healing of the secondary phase. Gumma. Pathologic features and joint immobilization may result. Tertiary (with lesions of deep organs following a latent period of 2 to 20 years or more). A latent stage of long duration is followed in 35% of cases by tertiary syphilis. Morphology In primary Syphilis. The chancre develops at the site of inoculation in 10 to 90 days (average 21 days) and has a characteristic “luetic vasculitis”. necrotic material and margins composed of plump or palisaded macrophages and fibroblasts surrounded by large numbers of mononuclear leukocytes. offer striking contrasts. Primary (the chancre). but the important effect is expanding aneurysm formation. Neurological Syphilis. reddened papule. and lymphadenitis is called primary syphilitic complex. atrophy of convolutions. Histologically. the central nervous system. The combination of chancre. generalized lymphadenopathy. The main forms are: 1. 3. tabes dorsalis. There are constitutional effects – particularly fiver and anemia. Stages of syphilis: 1.191 SYPHILIS Syphilis (lues) is a sexually transmitted disease of mankind caused by the spirochette Treponema pallidum. damage to various individual organs and tissues. Tertiary (Late) Syphilis. and the liver. or focal epithelioid granulomas. lymphangitis. b) Tabes dorsales – the damage specifically affected the posterior roots and columns of spinal cord – is associated with characteristic clinical symptoms due to lose of proprioceptive sensation in the legs. the result of cell-mediated immune reactions (T-cells) causing necrosis of tissue. gumma may produce the coarsely nodular pattern of cirrhosis. enlargement of ventricales. Secondary (disseminated). The regional nodes are usually enlarged and may show nonspecific acute or chronic lymphadenitis. the chancre contains an intense infiltrate of plasma cells. and general paresis. 2. in which endothelial cells proliferate and swell. Neurosyphilis takes one of several forms. and the walls of the vessels become thickened by lymphocytes and fibrous tissue. bones and testes (gummas).  Meningovascular – mainly affects the meningeal blood vessels and causes neurological impairment secondary  Parenchymatous: a) General paralysis of the insane – severe destruction of cerebral tissue. thus simulating a tumor  Histologically.

are stipulated by generalization of infection and inadequate reaction of organism on the infection. Local changes. the characteristic saddle nose deformity. in some cases it is absent. Hyperergic reaction of the organism on infects and absence of immunity stimulates generalization of infection. fungi and other agents. tuberculosis mycobacteria. and chronic. subacute. anemia stimulates the hemorrhagic syndrome. In perinatal and infantile Syphilis.  Clinical features . as it is observed in many infections. even in early cases. and acute polypous-ulcerative endocarditis with the tissue melting and tearing off of the valve. inflammatory and hyperplastic character. meningococci. and eight-nerve deafness.  Local changes occur by the primary focus of infection (portal of entry) or at some distance. 2. The incidence of sepsis has increased recently which is associated with the appearance of antibiotic-resistant strains of bacteria and administration of cytostatic preparations causing immune system insufficiency.and microorganism.  Vasculitis. hepatitis. lymphothrombosis and lymphadenitis.  The infection propagates from the focus through the lymph and blood vessels. progressing to thrombobacterial embolism. The duration of the disease is different (from some days to several months and even years).  Immunologic peculiarity of the sepsis is that immunity is not formed at this disease. very acute. not infectious illness. General changes  General changes at sepsis have degenerative.  Degenerative changes develop in parenchymatous organs and often finish by the necrosis. Periostitis of the tibia leads to excessive new bone growth on the anterior surfaces and anterior bowing.  The course of the disease is not cyclic.  There is no certain incubate period. or saber shin. The liver is often affected severely in congenital syphilis. pneumococci. inadequate reaction on the activator develops. increasing of vascular permeability.192 Congential syphilis is most severe when the mother‟s infection is recent. hyperergic reaction prevails. intoxication. The death rate in sepsis is very high. myocarditis. it cannot be reproduced experimentally.e. prevalence of general reaction and losses of the ability to locate infection.  Inflammatory changes are represented by interstitial septic nephritis. but also phlebitis and thrombophlebitis quickly develop. later on. The late-occurring form of congenital syphilis is distinctive for the triad of interstitial keratitis. typhoid bacilli.  There is purulent thrombophlebitis. acyclic course.  Epidemiological feature is polyetiology (except viruses). i. except for viruses).irrespective of the character of the activator displays of illness are stereotyped.  Lymphangitis. streptococci.  The inflammatory processes in parenchymatous organs and vessels occur. acute. Syphilitic osteochondritis and periostitis affect all bones. a diffuse rash develops. Diffuse fibrosis permeates lobules to isolate hepatic cells into small nests. .  Sepsis is severe disease with high lethality. significance of which is equivalent. that is why some forms of the disease may be defined. Destruction of the vomer causes collapse of the bridge of the nose and. Hutchinson's teeth. SEPSIS Sepsis is general infectious disease caused by infections getting into the organism and differs from other infectious diseases. blue pus bacilli. Sepsis may be cause by different causative agents (staphylococci.  Usually it is a focus of purulent inflammation. Morphology 1. Gummas are occasionally found in the liver.  Sepsis is not contagious. The lungs may be affected by a diffuse interstitial fibrosis. sometimes with no changes. Pathogenesis   Sepsis is a special form of interaction of macro.  Morphological feature is the fact that the local and general changes have no specific features as it is observed in many infections.

delirium) are characteristic. Hyperplastic processes in histiocyte-macrophage system are the cause of the liver enlargement.  Umbilical. for which toxicosis (high temperature. In blood leukocytosis and. with pulp scraping (“septic spleen”). it is usual in the entrance of infection with purulent lymphangitis and lymphadenitis. fibrinoid changes in the vessels.193        Hyperplastic processes develop in blood-creating and lymphatic tissues. tuberculous. infiltration by neutrophils. . According to portal of entry of infectious agent (location of the septic focus). Peripheral lymphonodes are increased. According to the etiology: staphylococcal. Hemorrhagic syndrome is well pronounced (petechial rash. Proliferation of lymphoid and reticular cells as well as accumulation of mature and immature blood cells are found in the spleen and lymph nodes. flabby on cut and of red color. meningococcal. Hemolytic jaundice may result from hemolytic action of some bacterial toxins. Hyperplasia of lymphoid and hemopoietic system is typical: the spleen is enlarged. Bone marrow hyperplasia occurs in the flat bones. Septicemia            It is a form of sepsis. The skin and sclera are usually yellow (hemolytic jaundice). The stroma of the organs is edematous. liver. hyperergy signs are moderate. septic endocarditis and chronic septicemia. Spleen produces large scrap of pulp (“septic splenitis”).  Otogenic. blue pus bacillus and association of these microorganisms. kidneys). anthracic. main attributes of which are purulent processes in the entrance of infection and bacterial embolism with formation of abscesses in many organs and tissues. absence of purulent metastases and rapid course. sometimes. the so-called leukemoid reaction develops. The etiology is frequently streptococcus. Septicemia is also characterized by increased vascular permeability. spleen is acutely increased. colibacillary. allergic vasculitis that is responsible for hemorrhagic syndrome. Septicopyemia     It is the form of sepsis. The yellow bone marrow of the tubular bones becomes red.  Surgical. Hyperplastic processes in sepsis are observed mainly in the hemopoietic and lymphoid tissue. Classification of sepsis A number of features are taken into account in classification. II. Interstitial inflammation develops in the parenchymal organs (heart. The foci of extramedullar hemopoiesis appear. According to the clinical-morphologic forms of sepsis: septicemia. immature leukocytes are found. In contrast to septicemia.  Tonsilogenic sepsis. and histiocytes is noted.  Odontogenic. Increased hemopoiesis with formation of a large number of immature forms is noted in the bone marrow of the flat bones and in the diaphyses of the bones. I. pneumococcal.  Cryptogenous (portal of entry of infectious agent is absent).  Uterine. The lymph nodes are also enlarged. the course of the disease is not very acute. III. At the dissection there is primary septic focus. increased reactivity of organism (hyperergia). septicopyemia. Primary septic focus is frequently absent.  Pulmonary. lymphocytes. The development is assosiated with staphylococcus and blue pus bacillus.  Therapeutic (parainfectious). gonococcal. hemorrhages to the serous and mucous membranes and internal organs).

 Developed on changed valves (defective) . ulcerative defects are seen in the sclerotic and deformed cusps of the valves. then in the liver. Depending on the presence of the background disease. The presence of primary septic focus on valves of the heart stimulates hyperergic damage of cardiac . Interstitial inflammation in parenchymatous organs is moderate or is absent. subcutaneous fat. b) Nodular thickening on the palm surface of the hand (“Osler’s nodes”). the disease involves the aortic intima. Hyperergia occurs and it can be considered to be bacterial septicemia.  Chronic (months and years). septic endocarditis (especially subacute and acute) is divided into 2 types:  On unchanged valves (intact valves) -primary septic endocarditis (Chernogybov’s disease). infarctions are observed in different organs. in 20. cellular reactions of stroma are marked. The plaques are easily crumbled and are saturated with calcium. aneurysm) and thromboembolism. Thrombotic plaques are located not only on the cusps but also on the parietal endocardium. hemorrhages. The most often causative agents are staphylococcus albus.vascular system. streptococcus viridian. In liver abscess. containing antigen of activator and causing to generalized vasculitis. Morphology            Polypous-ulcerative endocarditis develops on both sclerotic and intact valves. Spleen is septic. In the basis of hyperergia reactions of hypersensitivity lays. After removal of the plaques. skin abscess is complicated with phlegmon. bone marrow (purulent osteomyelitis).194       The purulent thrombophlebitis in the primary septic focus is a source of thrombobacterial embolism. At first metastatic abscesses appear in the lungs. The lymphatic nodes are not increased. Large thromboembolic polyp-shaped plaques appear on sclerotic valves. which causes the creation of metastatic abscesses in organs. When the aortic valves are injured. the heart valves (acute septic polypous-ulcerative endocarditis). Interstitial inflammatory processes. thromboembolic syndrome.and paranephritis. Infarctions and postinfarction scars are frequently observed. Kidney abscesses are complicated with peri. . and enterococcus. stimulated by toxic immune complexes circulating in the blood. Besides. c) Thickening of the nail phalanges (“drum sticks”). The spleen is enlarged due to prolonged pulp hyperplasia. purulent peritonitis develops. Septic (bacterial) endocarditis       It is the form of sepsis. Classification According to the character of course:  Acute (about 2 weeks). there are infarcts in the organ.  Subacute (till 3 months).secondary septic endocarditis in 70-80 % of cases. vasculitis. Immune-complex diffuse glomerulonephritis develops in the kidneys. Increasing of vascular pemerability. aureus. purulent pleuritis and pericarditis develop in the cases of lung abscess. synovial membranes (purulent arthritis). for which septic lesion of valves of the heart is characteristic. which is characteristic for the disease. Hyperplastic processes in blood-creating lymphatic tissue are expressed more poorly. The foci of softening and hemorrhages are observed in the brain due to vascular changes (vasculitis. The so-called peripheral signs of septic endocarditis are a) Petechial hemorrhages in the conjunctiva near the internal angle of the lower eyelid (“Lukin-Libman spots”). kidneys (apostematous nephritis).30 % of cases.

It results from the spread of microbes from severe localized infections (e. and that is why oliguria. peritonitis.. Thromboembolic complications are frequent. The lungs are seldom affected in pure hypovolemic shock because they are resistant to hypoxic injury. sometimes appear in all forms of shock. tonsils but more frequently they are large suppurations resulting from wounds. thromboendocarditis is most commonly localized in the left heart. The term zonal lesions refers to apparent hypercontraction of a myocyte. not healing primary septic focus. Shock is characterized by hypoxic failure of multiple organ systems. distortion of the myofilaments. 3. Pseudomonas aeruginosa. The renal changes are referred to as acute tubular necrosis.  The majority of cases are caused by endotoxin-producing gram-negative bacilli . lungs. causing to intoxication. An initial nonprogressive phase during which reflex compensatory mechanisms are activated and perfusion of the vital organs is preserved. gangrene of the extremities. A progressive stage characterized by tissue hypoperfusion and onset of an everwidening circle of circulatory and metabolic imbalances.  Shock is a progressive disorder that may lead to death. heart. dehydration are expressed. foci of softening in the brain. Brown atrophy is found in the liver. retina. including shortening and scalloping of the sarcomere. Morphology       These reactive features are nonspecific and are present in most bacterial septicemias. Serratia. progressing exhaustion (cachexia) and amyloidosis take place.g. and certain fungi. . The kidneys may be severely affected in shock. adrenals and gastrointestinal tract. suppuration in the tissue is absent which suggests hyperergic reaction of the organism in septic endocarditis. 2. In organs and tissues there is atrophy. abscess. an irreversible stage that sets in after the body has incurred cellular and tissue injury so severe that even if therapy corrects the hemodynamic defects survival is not possible. f) Jaundice. and Bacteroides . spleen. e) Hemorrhages to the skin and subcutaneous fat (Jeinway’s spots). In spite of the presence of streptococci in the thrombi. kidneys.coli. Proteus species. and electrolyte disturbances constitute major clinical problems. or “zonal lesions”. fragmentation of the Z band. Shock tends to evolve through three stages: 1. as the source of thromboembolism.E. and displacement of the mitochondria away from the intercalated disc. The spleen is decreased. Klebsiella pneumonia. Septic shock   Septic shock is currently the most common cause of death in intensive care units. The embolisms give the rise to infarctions in the lungs. such as pneumococci and streptococci.195     d) Necrotic foci in the subcutaneous fat. These septic foci can be found in carious teeth. Extensive purulent processes. but when the vascular collapse is caused by bacterial sepsis or trauma. Gram-positive cocci. The heart may undergo a variety of changes. In the brain the so-called ischemic encephalopathy may develop. Chronic septicemia       This form of sepsis is characterised by durably availability. and striated muscles. Subendocardial hemorrhages and necrosis. kidneys. and hence the cellular changes may appear in any tissue. liver. They are particularly evident in the brain. Thromboembolism frequently becomes generalized and dominates in the clinical picture of the disease. myocardium.hence the term endotoxic shock. intestine. anuria. pneumonia) into the bloodstream. consisting of a toxic lipid A core component and a complex polysaccharide coat. spleen. In finally. and skin necrosis.  Endotoxins are bacterial wall polysaccharides. as well as gram-positive bacterial toxins produce a similar syndrome.

Lymphoid hyperplasia with germinal center formation is pronounced. The adrenal alterations encountered in shock comprise in essence those common to all forms of stress and so might be referred to as “ the stress response”. of course. They are referred to as the acute respiratory distress syndrome. However. It is evident that postshock course of the patient does not lack for threats to life. The gastrointestinal tract may suffer patchy mucosal hemorrhages and necroses referred to as “hemorrhagic enteropathy”. The abscesses of the liver may take place also. most patients who suffer shock so severe as to produce irreversible changes succumb before these alterations become well developed. loss of neurons from the brain and of the myocytes from the heart is. Virtually all of these organs changes may revert to normal if the patient survives. Histiocytic hyperplasia is equally prominent. and plasma cell hyperplasia is present in the marginal zone of the white pulp and in the cords. The spleen is enlarged and soft. Splenomegaly of moderate degree (250 to 350 g) is common in acute systemic infections and is referred to as “acute reactive hyperplasia” or “septic splenitis”. irreversible. and the cut surface demonstrates an equal prominence of the red and white pulp. However. .196       changes may appear that are referred to as “shock lung”. The prognosis varies with the origin of shock and its duration.

. Thomas C. 13. Серов В. – 386 p. Kotran. WB Saunders company. – 687 с. 10. – Toronto – Philadelphia. Патологическая анатомия. .: Медицина. 1994 . 1989. Short lectures on pathology (pathological anatomy). 1998. – 640 с. Струков А.B. – Kharkiv: Tornado. 3rd ed. Руководство к практическим занятиям по патологической анатомии.K. Серов В. W. Cotran RS.222 p.В. Histopathology.Toronto – Philadelphia. – B..Toronto – Philadelphia. Philadelphia. 2000. Sorokina I.V. – М.197 LITERATURE 1. 6th ed. CSMU. – B. 1998. 14. Zagorulko A. Anderson’s Pathology // Edited by John M.. Rosai J: Ackerman's Surgical Pathology (2 vols). Robbins. 1999. Rubin E. Vinay Kumar. 7th ed.М. Lowe J: Pathology. Churchill Livingstone.В. 3. St Louis. Yakovtsova A. 8. Серов В. 2.Н. . Dacie JV. 1990. London. – Simferopol: 2 ed. JB Lippincott Company.C. Пальцев М.-254p. 1995.А. Патологическая анатомия. 1992. Mosby Company. Kumar V.F.C. Курс лекций. Saunders Company. 5. Heptinstall RH: Pathology of the Kidney (3 vols). 1991. 2002 . Thomas C. London. 6. 1997. 1st ed.: Медицина.А.V. Mosby. Пальцев М. 12.: Медицина. Robbins SL: Basic Pathology. 1993. 7. 9. 15. Little. . Kissane. Decker Inc. London. Stanley S. Philadelphia. Учебное пособие. . USA. Ramzi S.1400 p. Decker Inc. 8th ed. Mosby.М.В. The C. Farber JL: Pathology. 1999. Ганзен Т. Lewis SM: Practical Haematology..И. . – 980 p. 11.. 4. Lectures in Pathological anatomy. Stevens A. 1990. Macropathology. –355 p. Brown and Company. – 544 с. Robbins Pathologic Basis of Disease.

EXTRACELLULAR ACCUMULATIONS (MESENCHYMAL DEGENERATIONS) IV. TUMORS OF NERVOUS SYSTEM AND BRAIN MEMBRANES XV. TUMOROUS DISEASES OF BLOOD AND LYMPHATIC SYSTEMS: Leukemias Lymphomas PART II. INTRACELLULAR ACCUMULATIONS (PARENCHYMAL DEGENERATIONS OR DYSTROPHIES) III. SYSTEMIC PATHOLOGY I. HEMODYNAMIC DISTURBANCES: Hyperemia and congestion Hemorrhage Ischemia Infarction Stasis Thrombosis Embolism Shock Disseminated intravascular coagulation Edema VIII. MESENCHYMAL TUMORS XIV.CELLULAR ADAPTATIONS: Atrophy Hypertrophy and hyperplasia Metaplasia Dysplasia Healing Repair VII. IRREVERSIBLE CELLULAR INJURY: necrosis and apoptosis VI. INTRODUCTION ON PATHOLOGY CELLULAR INJURY AND CELLULAR DEATH II. DISEASES OF BLOOD AND LYMPHATIC SYSTEMS: . INFLAMMATION: Acute inflammation CHRONIC INFLAMMATION SYPHILIS IX. TUMORS OF MELANIN-PRODUCING TISSUE XVI. NEOPLASIA (General pathomorphology of neoplasia) XI. Mineral metabolism disturbance V. PATHOLOGY OF PIGMENTS. IMMUNOPATHOLOGY X. EPITHELIAL TUMORS XII. THE MOST OFTEN TUMORS XIII. GENERAL PATHOLOGY I.198 CONTENTS PART I.

DISEASES OF RESPIRATORY SYSTEM: ACUTE BACTERIAL INFECTIONS OF THE LUNGS: Pneumonias CHRONIC OBSTRUCTIVE PULMONARY DISEASE: Chronic Bronchitis Bronchiectasis (BE) Emphysema Bronchial Asthma (BA) Chronic Lung Abscess (LA) Idiopathic Pulmonary Fibrosis V. DISEASES OF CARDIOVASCULAR SYSTEM: Atherosklerosis Hypertension Ischemic heart disease: acute and chronic III. RHEUMATIC DISEASES: Rheumatic fever (RF) and Rheumatic heart disease (RHD) Rheumatoid Arthritis Systemic Lupus Erythematosus (SLE) Bechterew's disease Systemic scleroderma Dermatomyositis IV. DISEASES OF KIDNEY AND URINARY TRACT Glomerular Diseases Nephrotic Syndrome Tubulopathy Acute Tubular Necrosis Tubulointerstitial Disease Pyelonephritis Urolitiasis Hydronephrosis Cystic Disease of kidneys Chronic renal failure VIII. DISEASES OF ALIMENTARY SYSTEMS Tonsillitis Gastritis Peptic Ulcer Disease Appendicitis VI.199 Anemias II. GENITAL TPACT DISEASES: Diseases of Cervix. DISEASES OF THE LIVER: Hepatosis Viral hepatitis Cirrhosis of Liver Alcoholic liver disease Cholelitiasis (Gallstones) Cholecyscitis Pancreatitis VII. Diseases of Endometrium Diseases of Fallopian tubes Diseases of Ovaries Obstetric pathology .

SEPSIS. AIDS.200 Bening diseases of Brest Diseases of mail genitalia IX. INFECTIOUS DISEASES: Viral Diseases. Bacterial infections of childhood Gastrointestinal infections Tuberculosis Syphilis XIII. DISEASES OF ENDOCRINE SYSTEM: Diseases of pituitary body Diseases of adrenal glands Diseases of Thyroid gland Diabetes mellitus X. PRENATAL PATHOLOGY: Gametopaties Blastopaties Embryopaties Fetopathies XI. PERINATAL PATHOLOGY XII. SEPTIC SHOCK .