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CRIMEAN STATE MEDICAL UNIVERSITY
NAMED AFTER S.I.GEORGIEVSKY
Digest on pathomorphology
Assistant of professor
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.
Z 143 О.Загорулько, Т.Філоненко
«Дайджест з патоморфології». – Сімферополь, 2007.-417с. – Мова англ.
«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 A.Zagorоulko, T.Filonenko
«Digest on pathomorphology». – Simferopol, 2007. – 417 p.
“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.
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.
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:
The acquired causes of disease comprise the vast majority of common diseases and can be further categorised as the follows:
Hypoxia and ischemia.
Physical agents (mechanical trauma, thermal trauma, ultraviolet and ionizing radiation, rapid changes in atmospheric pressure).
Chemical agents and drugs.
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:
Infiltration – redundant accumulation (deposition) of metabolites into the cells and extracellular matrix.
Decomposition (phanerosis) – disintegration of membranous structures of the cells and extracellular matrix.
Perverted synthesis - synthesis of abnormal substances in the cells and tissues.
Transformation – formation of one type of metabolism’s products from common initial substances for proteins, fats and carbohydrates.
(PARENCHYMAL DEGENERATIONS OR DYSTROPHIES)
Intracellular accumulations are the accumulation of abnormal amounts of various substances in the cells. The stockpiled substances fall into three categories:
1. A normal cellular constituent accumulated in excess, such as water, lipid, protein, and carbohydrates.
2. An abnormal substance such as mineral, or a product of abnormal metabolism.
3. A pigment or an infectious product.
Parenchymal degenerations occur in functional cells such as: cells of a liver, kidneys, a myocardium and are characterized by accumulation in their cytoplasm proteins, fats and carbohydrates. It is accompanied by decrease (reduction) of function of enzymic systems and occurrence of structural changes in cells. The most often causes of parenchymal dystrophies are hypoxia, the intoxication, and also enzymopathy - genetically determined diseases at which is observed an inconsistency of enzymic systems in cells. In result enzymopathy there is an accumulation in cells of any products of a metabolism. Such diseases are named as storage diseases.
Intracellular proteinous degenerations
There are four kinds of intracellular accumulations of proteins:
1. A granular degeneration (dystrophy). Macroscopical kind of organs at this dystrophy it is determined as “muddy or dim swelling”. At a section the organs are dim, swollen. Microscopical descriptions of cells on electronics level: presence of electrondense granules in cytoplasm of the cells.
2. Hyaline-drop degeneration (dystrophy) is characterized by the aggregation of small proteins granules into cytoplasm of cells. It is not determined macroscopically. This dystrophy occurs in kidneys, liver and myocardium. The cytoplasm of plasma cells shows pink hyaline inclusions called Russell's bodies representing synthesised immunoglobulins, the cytoplasm of hepatocytes shows eosinophilic globular deposits of a mutant protein. Mallory's body or alcoholic hyaline in the hepatocytes is intracellular accumulation of intermediate filaments of cytokeratin. The outcome is negative. The focal or total coagulative necrosis develops.
3. Hydropic (cloudy, vacuolar, balloon) degeneration is characterized by accumulation of water within the cell due to cytoplasmic vacuolation. The common causes include bacterial toxins, chemicals, poisons, burns, and high fever. The affected organ such as kidney, liver or heart muscle is enlarged. The cut surface bulges outwards and is slightly opaque. Microscopically: the cells are swollen and the microvasculature compressed. Small clear vacuoles are seen in the cells. These vacuoles represent distended cisternas of the endoplasmic reticulum. Ultrastructural changes in hydropic swelling include the following:
Dilation of endoplasmic reticulum.
Blebs on the plasma membrane.
Loss of fibrillanty of nucleolus.
The outcome is negative, because the focal or total colliquative cellular necrosis develops.
4. Keratoid (horney) degeneration is characterized by increase production of keratin substance. This process may be local and general. The intracellular keratin may be located in epidermis of skin, keratinic squamous epithelial cells, cervix, and esophagus. Leucoplakia means hyperkeratosis in mucosa. Leucoplakia may lead to malignization. For example: Squamous cell carcinoma with keratinization. The groups of keratinized cells can be found in the center of squamous cell carcinoma’s areas. These cell’s complexes here and there look like rose color homogenous found forms (“canceromatous perls”).
Intracellular fatty degenerations
Intracellular fatty degenerations are the abnormal accumulations of triglycerides within parenchymal cells. The heart, liver, kidneys are damaged most frequently.
The main cause of fatty degeneration is hypoxia, which may be due to:
Excess alcohol consumption (most commonly).
Chronic cardiovascular and chronic pulmonary insufficiency.
Infections (e.g. diphtheria, tuberculosis).
Late period of pregnancy.
Hepatotoxins (e. g. carbon tetrachloride, chloroform).
Certain drugs (e. g. administration of estrogen, steroids, tetracycline).
In the case of cell injury by chronic alcoholism, many factors are implicated with increased lipolysis, increased free fatty acid synthesis, decreased tryglyceride utilisation, decreased fatty acid oxidation to ketone bodies, and block in lipoprotein excretion.
An alcoholic who has not developed progressive fibrosis in the form of cirrhosis, the enlarged fatty liver may return to normal if the person becomes teetotaler.
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), oil red O and osmic acid.
1. Fatty degeneration of the liver
Macroscopically the fatty liver is enlarged with rounded margins.
The cut surface bulges slightly and is pale-yellow and is greasy to touch. It is called “goose liver”.
Microscopically: there are numerous lipid vacuoles in the cytoplasm of hepatocytes. The vacuoles are initially small (microvesicular), but with progression of the process, the vacuoles become larger pushing the nucleus to the periphery of the cells (macrovesicular).
At times, the hepatocytes laden with large lipid vacuoles may rupture and lipid vacuoles coalesce to form fatty cysts. Infrequently, lipogranulomas may appear.
2. Fatty degeneration of the heart
It is also called “Tiger’s” heart.
Macroscopically the heart is enlarged, the chambers are stretched, flabby.
Microscopically we can see dust-like fatty vacuoles in the cardiomyocytes.
It is observed in the papillary muscles and trabecules of the ventricles in the form of bands (surrounding the veins).
3. The kidneys look like “large white kidney”. They are enlarged, flabby. The cortical substance is gray with yellow drops.
Outcomes of fatty degenerations are seldom reversible. Necrosis or sclerosis may develop.
Intracellular carbohydrate degenerations
Carbohydrates are divided into 3 groups:
1. Polysaccharides (glycogen).
3. Glycoproteides (mucin, mucoid).
There are several special reactions for identification of these carbohydrates. Best’s carmine and PAS (periodic acid-Schiff) staining may be employed to confirm the presence of glycogen in cells. Polysaccharides and mucopolysaccarides are stained dark pink or red. Staining according to Haile - for identification glycoproteides. Glycoproteides are stained blue.
Accumulations of glycogen
Accumulations of glycogen are excessive intracellular deposits of glycogen usually in patients with an abnormality of either glucose or glycogen metabolism.
Morphological features – appearance of glycogen masses as clear vacuoles within the cytoplasm developed with special stain – PAS-reaction.
In diabetes mellitus - 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.
Amount of glycogen in the tissues reduces sharply (e.g. in the liver) which causes its fat infiltration (fatty liver degeneration).
Mucus secreted by mucous glands is a combination of proteins complexes with mucopolysaccharides Mucin, a glycoprotein, is its main constituent. Mucin is normally produced by epithelial cells of mucous membranes and mucous glands, as well as by some connective tissues like in the umbilical cord. Epithelial mucin is stained positively with periodic acid-Shiff (PAS), while connective tissue mucin does not but is stained positively with colloidal iron. Both are, however, stained by alcian blue.
Epithelial mucin is associated with:
Catarrhal inflammation of mucous membrane (e. g. of respiratory tract, alimentary tract, uterus).
Obstruction of duct leading to mucocele in the oral cavity, chronic appendicitis and gall bladder.
Cystic fibrosis of the pancreas or mucoviscidosis.
Mucin-secreting tumors (e. g. of ovary, stomach, large bowel etc.).
There are a lot of diseases, which are due to hereditary factors and connected with metabolism disturbance. These diseases are called storage diseases or enzymopathy.
A few general comments can be made about all storage diseases:
All the storage diseases occur as a result of autosomal recessive, or sex-(X-) linked recessive genetic transmission.
Most of the storage diseases are lysosomal storage diseases. Out of the glycogen storage diseases, 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:
The type of proteinoses, lipidosis and glycogenoses depends on the defect in the enzyme. The most frequent lipidosis are Gaucher’s disease, Niemann-Pick disease.
This is an autosomal recessive disorder in which there is deficiency of lysosomal enzyme, glucocerebrosidase, which normally cleaves glucose from ceramide. This results in lysosomal accumulation of glucocerebroside (ceramide-glucose) in phagocytes of the body and sometimes in the neurons. 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, while the deposits in the neurons consist of gangliosides.
Clinically, there are 3 types of Gaucher’s disease:
1. 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, principally involving the spleen, liver, bone marrow and lymph nodes. This is the most common type comprising 80% of all cases of Gaucher’s disease.
2. Type II is the infantile form in which there is progressive involvement of the central nervous system.
3. Type III is the juvenile form of the disease having features in between type I and type II, i.e. they have systemic involvement like in type I and progressive involvement of the central nervous system (CNS) as in type II.
In addition to involvement of different organs and systems (splenomegaly, hepatomegaly, lymphadenopathy, bone marrow and cerebral involvement), a few other features include pancytopenia, or thrombocytopenia secondary to hypersplenism, bone pains and pathologic fractures.
Microscopically large number of characteristically distended and enlarged macrophages called Gaucher cells which are found in the spleen, liver, bone marrow and lymph nodes, and in the case of neuronal involvement, in the Virchow-Robin space. The cytoplasm of these cells is abundant, granular and fibrillar resembling crumpled tissue paper. They have mostly a single nucleus but occasionally may have two or three nuclei. These cells often show erythrophagocytosis and are rich in acid phosphatase.
This is also an autosomal recessive disorder characterized by accumulation of sphingomyelin and cholesterol.
Majority of the cases (about 80%) have deficiency of sphingomyelinase, which is required for cleavage of sphingomyelin, while a few cases probably result from deficiency of an activator protein.
The condition presents in infancy and is characterized by hepatosplenomegaly, lymphadenopathy and physical and mental underdevelopment.
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, particularly in the cells of mononuclear phagocyte system.
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.
These cells are located in the spleen, liver, lymph nodes, bone marrow, lungs, intestine and brain.
The most frequent glycogen storage diseases or glycogenosis are Pompe’s disease, Mc Ardle’s disease and Gierke disease. There is defective metabolism of glycogen due to genetic disorders.
Pompe’s Disease. This is also an autosomal recessive disorder due to deficiency of a lysosomal enzyme, acid mahase. Its deficiency results in accumulation of glycogen in many tissues, most often in the heart and skeletal muscles leading to cardiomegaly and hypotonia.
Mc Ardle’s Disease. The condition occurs due to deficiency of muscle phosphorylase resulting in accumulation of glycogen in the muscle (deficiency of liver phosphorylase). The disease is common in 2nd to 4th decades of life and is characterized by painful muscle cramps, especially after exercise, and detection of myoglobinuria in half the cases.
Gierke Disease. This condition is inherited as an autosomal recessive disorder due to deficiency of enzyme, glucose-6-phosphatase. In the absence of glucose-6-phosphatase, excess of normal type of glycogen accumulates in the liver and also results in hypoglycemia due to reduced formation of free glucose from glycogen. As results, fat is metabolized for energy requirement leading to hyperlipoproteinemia and ketosis. Other changes due to deranged glucose metabolism are hyperuricemia. The disease manifests clinically in infancy with failure to thrive and stunted growth. Most prominent feature is enormous hepatomegaly with intracytoplasmic and intranuclear glycogen. The kidneys are also enlarged and show intracytoplasmic glycogen in tubular epithelial cells. Other features include gout, skin xanthomas and bleeding tendencies due to platelet dysfunction.
The outcome of storage diseases is unfavorable because of insufficienty of the respective organ.
Mescnchymal (stromal vascular) degenerations develop in the connective tissue as a result of metabolic disturbances in it.
Stromal vascular proteinous degenerations
Proteinous mesenchymal degenerations occur as mucoid swelling, fibrinoid changes, hyalinosis and amyloidosis.
The first three types are the stages of connective tissue disorganization. The causes of mucoid swelling, fibrinous changes and hyalinosis are the same as they are the stages of one process. They are immunopathological and autoimmune states, hypoxia, infections. These types of connective tissue disorganization are frequently observed in hypertension, rheumatism and other diseases of the connective tissue accompanied by immune disturbances as well as in allergic diseases, diabetes mellitus, etc. In the majority of cases the arterial walls, heart valves, endocardium, epicardium, articular connective tissue are involved.
1. Mucoid swelling
Mucoid swelling is superficial reversible disorganization of the connective tissue.
These processes are associated with swelling of collagen fibers, increased vascular permeability (due to glucosaminoglycans (GAG) action) and plasmorrhagia.
Microscopic examination shows metachromasia. Under normal conditions the main substance is basophilic. In this case staining with toluidine blue demonstrates reddish coloring.
Macroscopic appearance is absent.
The outcome may be reversible. In other cases, the development of fibrinoid swelling is possible.
2. Fibrinoid changes
Fibrinoid swelling is deep irreversible connective tissue disorganization.
Fibrinoid is formed as a result of the main substance destruction and more increase in vascular permeability.
The appearance of the organs is changed a little.
The main signs are revealed microscopically: the bands of collagen fibers are homogenous, impregnated with plasma proteins.
Metachromasia is not marked due to GAG depolymerization of the main substance.
Fibrinoid swelling may be generalized (in systemic diseases of the connective tissue) and localized (in chronic inflammations).
The outcomes are fibrinoid necrosis, sclerosis or hyalinosis.
3. Hyaline changes (hyalinosis)
Hyaline changes (hyalinosis) - (greek “hyalos” - transparent, glass-like) usually refers to an alteration within cells or in the extracellular matrix, which gives a homogenous, glassy, pink appearance in routine histologic sections stained with hematoxilin and eosin.
Hyalinosis develops as a result of plasma infiltration, fibrinoid swelling, inflammation, necrosis, and sclerosis.
Hyalinosis is classified according to its localization (vascular hyalinosis and connective tissue hyalinosis) and propagation (generalized and localized).
Vascular hyalinosis involves the arterioles and small arteries. In their walls, the endothelium, basement membranes, and smooth muscle cells are damaged.
Three types of vascular hyaline are distinguished depending on the pathogenetie character of its formation: 1) simple, 2) lipohyaline, 3) compound hyaline.
Microscopic study of the arteries demonstrates thickened walls with sharply narrowed or obliterated lumen. At first, hyaline is accumulated in subendothelial areas of the vascular wall, and then it destroys elastic and middle membranes.
In long-standing hypertension and diabetes mellitus, the walls of arterioles, especially in the kidney, become hyalinized, owing to extravasated plasma’s protein and deposition of basement membrane material.
Hyalinosis of connective tissue is usually localized; it develops in scars, adhesions, in the areas of chronic inflammation (e.g. “glazed spleen”).
The outcome of hyalinosis is irreversible.
Functional significance of hyalin is different. Thus, vascular hyalinosis may lead to atrophy or sclerosis, infarction of organs. Local hyalinosis in the cardiac valves results in heart defects.
Amyloidosis is the term used for a group of diseases characterised by extracellular deposition of fibrillar proteinaceous substance called amyloid.
Nature and etiology
Amyloid is composed of 2 main types of complex proteins:
1. Fibril proteins comprising about 90% of amyloid.
2. P-componentconstituting the remaining 10% of amyloid.
By electron microscopy the major component of amyloid material (about 90%) consists of meshwork of fibril proteins. 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. AL protein of fibrils consists of polypeptides, which may be made up of whole immunoglobulm light chains or fragment of light chains. AL type of fibril protein is produced by immunoglobulin-secreting cells and is, therefore, seen in association with plasma cell dyscrasias. The stimulus for production of AL-amyloid is some disorder of immunoglobulin synthesis (multiple myeloma). B-cell lymphoma, other plasma cells dyscrasias.
AA (amyloid associated) protein. AA protein consists of polypeptides having 76 amino acids and is derived from larger precursor protein in the serum called SAA (serum amyloid-associated protein). In the plasma SAA circulates in association with HDL3 (high-density lipoprotein). SAA is an acute phase reactant protein synthesised in the liver, its level being high in chronic inflammatory and traumatic conditions. It may be in chronic mflammation and cancer, familial Mediterranean fever.
Other proteins. 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.
A2-microglobulm (A2m) is amyloid seen in cases on long-term hemodialysis (8-10 years).
-amyloid protein (A) is distinctive from A2m and is seen in cerebral plaques as well as cerebral blood vessels in Alzheimer’s disease.
Hormone precursor such as procalcitonin and pro-insulin (amyloid endocrine) and keratin has also been reported in amyloid.
The second component of amyloid is non-fibnllar P-component that constitutes about 10% of amyloid material. It is synthesised in the liver and is present in all types of amyloid. 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. According to this classification, amyloidosis can be divided into 2 major categories each found in distinct clinical settings.
A. Systemic Amyloidosis
1. Primary amyloidosis.
This is one of the two types of systemic or generalised amyloidosis.
Primary amyloidosis associates with plasma cell dyscrasias and conteins AL-protein.
In the 25% to 40% of these cases, primary amyloidosis is the high binger of frank plasma cell neoplasia, such as multiple myeloma or other B-cell lymphomas.
Primary amyloidosis is often severe in the heart, bowel, skin, skeletal muscle, and less often in the solid abdominal viscera.
This type of amyloidosis is most common form in the world.
2. Secondary (reactive) amyloidosis.
The second form of systemic or generalised amyloidosis is reactive or secondary in which the fibril proteins contain AA amyloid.
Secondary or reactive amyloidosis occurs as a complication of chronic infectious or noninfectious inflammatory conditions associated with tissues destruction such as tuberculosis, bronchiectasis, chronic osteomyelitis, chronic pyelonephritis, leprosy, autoimmune disorders (rheumatoid arthritis, dermatomyositis and scleroderma), inflammatory bowel disease (ulcerative colitis and Crohn’s disease) and some tumors (renal cell carcinoma and Hodgkin’s disease).
Secondary amyloidosis is typically distributed in solid abdominal viscera like the liver, spleen, kidneys and adrenals Secondary reactive amyloidosis is seen less frequently in developed countries due to containment of infections before they become chronic, but this is the most common type of amyloidosis in underdeveloped and developing countries of the world.
3. Familial amyloidosis.
Familial amyloidosis is seen in patients with familial Mediterranean fever and familial amyloidotic polyneuropathy.
Familial Mediterranean fever is an autosomal recessive disease. The condition is characterised by periodic attacks of fever and polyserositis.
Amyloidosis occurring in these cases is AA type.
Hereditary polyneuropathic amyloidosis is an autosomal dominant disorder in which amyloid is deposited in the peripheral and autonomic nerves.
B. Localized Amyloidosis
Senile cardiac amyloidosis is seen in 50% of people above the age of 70 years. The deposits are seen in the heart and aorta.
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. Patients of Alzheimer’s disease also develop amyloid in the senile plaques.
Endocrine amyloidosis. Some endocrine tumors are associated with microscopic deposits of amyloid in medullary carcinoma of the thyroid, and islet cell tumor of the pancreas.
Macroscopically, the affected organs are often enlarged and firm and have a waxy appearance. If the deposits are sufficiently large, painting the cut surface with iodine imparts a yellow color that is transformed to blue violet after application of sulfuric acid.
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, homogeneous, structureless and eosinophilic hyaline material
Metachromatic stains (Rosaniline Dyes). Amyloid has the property of metachromasia, i. e. the dye reacts with amyloid and undergoes a color change. Metachromatic stains employed are rosaniline dyes such as methyl-violet and crystal-violet, which impart rose-pink coloration to amyloid deposits.
Congo red. All types of amyloid have affinity for Congo red stain. The stain may be used on both gross specimens and microscopic sections amyloid stains an orange color. The stain can also be used to distinguish between AL and AA amyloid (primary and secondary amyloid respectively). After prior treatment with permangnate on the section, Congo red stain is repeated: in the case of primary amyloid (AL amyloid), the Congo red positivity (congophilia) persists while it turns negative for Congo red in secondary amyloid (AA amyloid).
Sulfated alcian blue. This is a nonspecitic screening test and imparts blue-green color to amyloid positive areas.
lmmunohistochemistry. More recently, immunohistochemical stains can classify type of amyloid. Antibody specific for fibril protein gives positive immunoreactivity.
Diagnosis of amyloidosis
Histologic examination of biopsy material is the commonest and confirmatory method for diagnosis in a suspected case of amyloidosis. If renal manifestations are present, kidney is the preferred site for biopsy. Otherwise the commonly accessible sites such as rectum, gingiva, and more recently abdominal fat, are biopsied and are followed by Congo red staining for confirmation.
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 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, enlarged or terminally contracted due to ischemic effect of narrowing of vascular lumina. Cut surface is pale waxy and translucent.
Amyloid deposition occurs primarily in the glomeruli though it may involve peritubular interstitial tissue and the walls of arterioles as well:
In the glomeruli, the deposits initially appear on the basement membrane of the glomerular capillaries, but later extend to produce luminal narrowing and distortion of the glomerular capillary tuft.
In the tubules, the amyloid deposits likewise begin close to the tubular epithelial basement membrane.
The vascular involvement affects chiefly the walls of small arterioles and venules, producing narrowing of their lumina and consequent ischemic effects.
Amyloidosis of Spleen
Two patterns are observed:
“Sago spleen”. The splenomegaly is not marked and cut surface shows characteristic translucent pale and waxy nodules resembling sago grains and hence the name. Microscopically, the amyloid deposits begin in the walls of the arterioles of the white pulp and may subsequently replace the follicles.
“Lardaceous spleen”. There is generally moderate to marked splenomegaly (weight up to 1 kg). Cut surface of the spleen shows map-like areas of amyloid. Microscopically, the deposits involve the walls of splenic sinuses and the small arteries and in the connective tissue of the red pulp.
Amyloidosis of Liver. The liver is often enlarged pale, waxy and firm. The amyloid initially appears in the space of Disse, but later as it increases; it compresses the cords of hepatocytes.
Amyloidosis of Heart.
Heart is involved in systemic amyloidosis quite commonly more so in the primary than in secondary systemic amyloidosis. It may also be involved in localised form of amyloidosis in very old patients.
Amyloidosis of the heart may produce arrhythmias due to deposition in the conduction’s system. The heart shows tiny nodular deposits of amyioid underneath the endocardium.
Later, there may be a pressure atrophy and impaired ventricular function, which may produce restrictive cardiomyopathy.
Amyloidosis of Alimentary tract. Involvement of the gastrointestinal tract by amyloidosis may occur at any level from the oral cavity to the anus. Rectal and gingival biopsies are the common sites for diagnosis of systemic amyloidosis.
The prognosis for patients with generalized amyloidosis is poor. Those with immunocyte-derived amyloidosis have a median survival of 2 years after diagnosis.
Stromal vascular fatty degenerations
Stromal fatty infiltration is the deposition of mature adipose cells in the stromal connective tissue. The condition occurs most often in patients with obesity.
As a rule it is a generalized process when the amount of fat in the depots increases.
Depending on the excess of the patient mass compared to the norm, 4 degrees of obesity are defined:
1. If the patient’s mass increases by 20 -29% we distinguish 1st degree of obesity;
2. If the patient's mass increases by 30 -49% - 2nd degree;
3. If the patient's mass increases by 50 - 99% - 3rd degree;
4. If the patient's mass increases by 100% and more 4th degree of obesity.
The two commonly affected organs are the heart and the pancreas.
The damage to these organs is most serious.
Subepicardial fat covers the heart as a case, invades the myocardial stroma causing atrophy and sclerosis.
If the connective tissue does not grow, heart rupture in the area of fat growth may occur.
In pancreatic lipomatosis beta-cell atrophy and diabetes mellitus are possible.
According to the etiology the following types of obesity are defined:
1. Primary (idiopathic);
There are several types of secondary obesity:
4. Hereditary in Gierke’s disease.
According to the patient's appearance, obesity may be
According to morphological peculiarities of adipose tissue, it may be:
In hypertrophic type adipose tissue enlarges due to increased volume of fatty cells, in hyperplastic due to increase in their number. Obesity is a severe complication of mainly endocrine and nervous diseases. Alimentary obesity is also unfavorable for the organism. As a rule such patients develop ischemic heart disease.
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.
Sharp reduction in the amount of neutral fat in the whole organism is called cachexia.
Disturbance in cholesterol and its esters metabolism causes atherosclerosis. The wall of the vessel is thicken everywhere, but much more it is thicken because of the formation of the atherosclerotic plaque, which are composed with lipids and fibrotic tissue.
Stromal vascular carbohydrate degenerations
Stromal vascular carbohydrate degenerations develop due to disturbance of glycosaminoglycans and glycoproteids metabolism. When glycoproteid metabolism is disturbed, chromotropic substances are released from the protein bonds. They accumulate in the main substance of the connective tissue. Collagen fibers change into mucus-like mass.
Connective tissue mucin is associated with:
Mucoid or myxoid degeneration in some tumors (myxomas).
Neurofibromas, soft tissue sarcomas etc.
Myxomatous change in the dermis in myxedema.
Myxoid change in the synovium in ganglion on the wrist.
The condition results in colliquative necrosis with formation of cavities filled with mucus.
Disturbance of glycosaminoglycans (GAG) is due to hereditary factors as in a storage disease.
It is characterized by deficiency of specific lysosomal enzyme involved in the degradation of mucopolysaccharides or glycosaminoglycans.
Syndrome of MPS manifests in infancy or early childhood and involves multiple organs and tissues, chiefly connective tissues, liver, spleen, bone marrow, lymph nodes, kidneys, heart and brain.
The mucopolysaccarides accumulate in mononuclear phagocytic cells, endothelial cells, smooth muscle cells and fibroblasts.
The material is finely granular and PAS-positive by light microscopy.
By electron microscopy, it appears in the swollen lysosomes and can be identified biochemically as mucopolysaccharide.
The most frequent of them are Pfaundler-Hurler disease, or gargoilism. Its cause is congenital defect of the enzyme determining GAG metabolism. This disease is characterized by irregular skeleton growth, “massive” skull, heart defects, inguinal and umbilical hernias, hepato- and splenomegaly, keratoleukoma (retina opacity).
PATHOLOGY OF PIGMENTS
Pigments are colored substances, some of which are normal constituents of cells where as others are abnormal and collect in cells only under special circumstances.
Pigments are generally classified into two broad categories:
Endogenous pigments, which are normal constituents of cells and tissues;
Exogenous pigments introduced into the body from environment.
Classification of endogenous pigments
1. Hemoglobinogenic pigments.
Pigments derived from hemoproteins appear as a result of physiologic destruction of erythrocytes.
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