INTRODUCTION CELLULAR RESPONSES And cell death Pathology is

Pathology is the study (logos) of disease (pathos). Study of the structural, biochemical,

pathology is divided into general pathology and systemic pathology. reactions of cells and

LIVER BIOSY IN AFLD Companion site for Molecular Pathology Copyright © 2009 by Academic

Disease process cause (etiology), the mechanisms of its development (pathogenesis), the biochemical and structural

hypertrophy Hypertrophy refers to an increase in the size of cells, resulting in an

Hypertrophy can be physiologic or pathologic increased functional demand or stimulation by hormones

Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved.

hyperplasia Hyperplasia is an increase in the number of cells in an organ or

Hyperplasia is the result of growth factor–driven proliferation of mature cells by increased

ATROPHY Atrophy is reduced size of an organ or tissue resulting from a decrease

CAUSES OF ATROPHY Loss of innervation (denervation atrophy Decreased workload (atrophy of disuse Diminished

With continuing damage the injury becomes irreversible, at which time the cell cannot

REVERSIBLE INJURY cellular swelling and fatty change. when cells can’t maintaining ionic and fluid

hallmarks of reversible injury are reduced oxidative phosphorylation with resultant depletion of energy

1. Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli 2.

A, Normal kidney tubules with viable epithelial cells. B, Early (reversible). C, Necrosis Companion

Necrosis denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell Necrotic

Morphology of necrosis Necrotic cells show increased eosinophilia loss of cytoplasmic RNA The necrotic

Nuclear changes The basophilia of the chromatin may fade (karyolysis), loss of DNA because

FIGURE 1. 1 Electron microscopy of oncotic necrosis to a rat hepatic sinusoidal endothelial

Coagulative necrosis architecture of dead tissues is preserved for a span of days. tissues

Myocardial infarction Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All

Liquefactive necrosis digestion of the dead cells, with a liquid viscous mass formation. seen

Liquefactive necrosis(brain) Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All

Gangrenous necrosis term is commonly used in clinical practice. Applied to a limb, generally

Caseous necrosis in foci of tuberculous infection “caseous” (cheeselike) is derived from the friable

Fat necrosis refers to focal areas of fat destruction, resulting from release of activated

Acute pancreatitis Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All

Fat necrosis Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All

Fibrinoid necrosis seen in immune reactions involving blood vessels. occurs when complexes of antigens

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INTRODUCTION CELLULAR RESPONSES And cell death

Pathology is the study (logos) of disease (pathos). Study of the structural, biochemical, and functional changes in cells, tissues, organs that underlie disease. Use of molecular, microbiologic, immunologic, and morphologic techniques. Signs and symptoms manifested by patients 2

pathology is divided into general pathology and systemic pathology. reactions of cells and tissues to abnormal stimuli and to inherited defects, the main causes of disease. (principles of general pathology ) the alterations in specialized organs and tissues responsible for disorders that involve these organs. (systemic pathology) 3

DIAGNOSTIC LAB 4

MOLECULAR TECHNIQUES IN DIAGNOSIS 6

Disease process cause (etiology), the mechanisms of its development (pathogenesis), the biochemical and structural alterations induced in the cells and organs of the body (molecular and morphologic changes), functional consequences of these changes (clinical manifestations). 7

Response to cell injury 8

Different cellular responses 9

hypertrophy Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ. The hypertrophied organ has no new cells, just larger cells. synthesis of more structural components of the cells 11

Hypertrophy can be physiologic or pathologic increased functional demand or stimulation by hormones and growth factors The most common stimulus for hypertrophy of muscle is increased workload. 12

hyperplasia Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue. triggered by the same stimulus. Hyperplasia takes place if the cell population is capable of dividing, physiologic or pathologic. 14

Hyperplasia is the result of growth factor–driven proliferation of mature cells by increased output of new cells from tissue stem cells. For instance, after partial hepatectomy growth factors are produced in the liver that engage receptors on the surviving cells and activate signaling pathways that stimulate cell proliferation. 15

Endometrial hyperplasia 16

ATROPHY Atrophy is reduced size of an organ or tissue resulting from a decrease in cell size and number. physiologic or pathologic. atrophy is common during normal development. Some embryonic structures, such as the notochord and thyroglossal duct, undergo atrophy during fetal development. uterus decreases in size shortly after parturition 18

CAUSES OF ATROPHY Loss of innervation (denervation atrophy Decreased workload (atrophy of disuse Diminished blood supply Inadequate nutrition. Loss of endocrine stimulation. Pressure 19

With continuing damage the injury becomes irreversible, at which time the cell cannot recover and it dies. There are two principal types of cell death, necrosis and apoptosis differ in their morphology, mechanisms, and roles in physiology and disease. 20

Necrosis and apoptosis 21

REVERSIBLE INJURY cellular swelling and fatty change. when cells can’t maintaining ionic and fluid homeostasis due to failure of energy-dependent ion pumps in the plasma membrane swelling occurs. Na-K ATPase 24

hallmarks of reversible injury are reduced oxidative phosphorylation with resultant depletion of energy stores in the form of adenosine triphosphate (ATP) Fatty change occurs in hypoxic injury and various forms of toxic or metabolic injury. appearance of lipid vacuoles in the cytoplasm. (hepatocytes and myocardial cells) 25

1. Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli 2. Mitochondrial changes, including swelling and the appearance of small amorphous densities 3. Dilation of the ER, with detachment of polysomes; intracytoplasmic myelin figures may be present 4. Nuclear alterations, with disaggregation of granular and fibrillar elements. 26

Necrosis denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell Necrotic cells are unable to maintain membrane integrity contents often leak out, elicit inflammation lysosomes of the dying cells themselves digest necrotic cells and lysosomes of leukocytes (inflammatory reaction). 28

Morphology of necrosis Necrotic cells show increased eosinophilia loss of cytoplasmic RNA The necrotic cell may have a more glassy homogeneous appearance than do normal cells, mainly as a result of the loss of glycogen particles enzymes digest the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears motheaten. 29

Nuclear changes The basophilia of the chromatin may fade (karyolysis), loss of DNA because of enzymatic degradation by endonucleases. pyknosis, characterized by nuclear shrinkage and increased basophilia. chromatin condenses into a solid, shrunken basophilic mass. karyorrhexis, the pyknotic nucleus undergoes fragmentation 30

FIGURE 1. 1 Electron microscopy of oncotic necrosis to a rat hepatic sinusoidal endothelial cell after ischemia/reperfusion. Note cell rounding, mitochondrial swelling (arrows), rarefaction of cytosol, dilatation of the ER and the space between the nuclear membranes (*), chromatin condensation, and discontinuities in the plasma membrane. Bar is 2 µ m. Companion site for Molecular Pathology Copyright © 2009 by Academic Press. All rights reserved. 31

Coagulative necrosis architecture of dead tissues is preserved for a span of days. tissues exhibit a firm texture. Injury denatures not only structural proteins but also enzymes so blocks the proteolysis of the dead cells eosinophilic, anucleate cells may persist for days or weeks. infarct 32

Liquefactive necrosis digestion of the dead cells, with a liquid viscous mass formation. seen in focal bacterial infect. microbes stimulate the accumulation of leukocytes and liberation of enzymes necrotic material creamy yellow (dead leukocytes) called pus. hypoxic death of cells (CNS) liquefactive necrosis 34

Gangrenous necrosis term is commonly used in clinical practice. Applied to a limb, generally the lower leg, lost its blood supply and has undergone necrosis (typically coagulative necrosis) involving multiple tissue planes. 37

Caseous necrosis in foci of tuberculous infection “caseous” (cheeselike) is derived from the friable white appearance of the area of necrosis. On microscopic examination, the necrotic area appears as a collection of fragmented or lysed cells amorphous granular debris enclosed within a distinctive inflammatory Border( granuloma) 38

Caseous necrosis lung 39

Fat necrosis refers to focal areas of fat destruction, resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. This occurs in the calamitous abdominal emergency known as acute pancreatitis 40

Fibrinoid necrosis seen in immune reactions involving blood vessels. occurs when complexes of antigens and antibodies are deposited in the walls of arteries. Deposits of these “immune complexes, ” together with fibrin (leaked out of vessels) called “fibrinoid” (fibrin-like) by pathologists ( 43