Transcript pathologic - Lectures For UG-5

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

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 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)
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DIAGNOSTIC LAB
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LIVER BIOSY IN AFLD
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MOLECULAR TECHNIQUES IN
DIAGNOSIS
MOLECULAR TECHNIQUES IN DIAGNOSIS
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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).
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Response to cell injury
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Different cellular responses
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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
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 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.
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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.
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 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.
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Endometrial hyperplasia
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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
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CAUSES OF ATROPHY
 Loss of innervation (denervation atrophy
 Decreased workload (atrophy of disuse
 Diminished blood supply
 Inadequate nutrition.
 Loss of endocrine stimulation.
 Pressure
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 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.
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Necrosis and apoptosis
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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
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 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)
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 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.
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A, Normal kidney tubules with viable epithelial
cells. B, Early (reversible). C, Necrosis
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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).
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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.
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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
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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 µm.
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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
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Myocardial infarction
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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
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Liquefactive necrosis(brain)
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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.
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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)
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Caseous necrosis lung
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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
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Acute pancreatitis
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Fat necrosis
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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 (
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