what is pathology? “scientific study of disease" or the alterations that occur when abnormal...
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What is Pathology?
•“Scientific study of disease" or the alterations that occur when abnormal influences (bacteria, viruses, etc.) affect cells, tissues, or body systems. More specifically, pathology may be defined as the "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents or
adverse influences".
Pathology Deals with…
• The causes of disease (etiology)
• Mechanisms of disease (pathogenesis)
• Structural alterations of cells and tissues
• Functional alteration and consequences of disease
Function of Pathology
Pathology serves as a "bridge" or "link" between the preclinical subjects (anatomy, physiology, etc.) and the courses in clinical medicine. Actually, pathology provides a logical means of relating the knowledge of normal structure and function (anatomy and physiology) to abnormal structure and function as encountered in a diseased animal.
General Pathology
•It explores and explains the development of basic pathologic mechanisms:
•Introduction to pathology•Inflammation, repair and regeneration ,
•Cell injury, degenerations and infiltrations •Haemodynamic (circulatory) disorders .
•Granulomatous inflammations .•Growth disorders and neoplasia.
Cell Injury and Necrosis
Causes of Cell Injury
•Oxygen Deprivation
•Physical Agents
•Chemical Agents and Drugs
•Infectious Agents
•Immunologic Reactions
•Genetic Derangements
•Nutritional Imbalances
Oxygen Deprivation
•Hypoxia – deficiency of oxygen
•Ischemia – loss of blood supply (arterial flow or reduced venous drainage)
Causes of Cell InjuryCauses of Cell Injury
Physical Agents
•Mechanical trauma
•Extremes of temperature – burns, deep cold
•Radiation
•Electric shock
Causes of Cell InjuryCauses of Cell Injury
Chemical Agents and Drugs
•Hypertonic concentration of salt – deranging electrolyte homeostasis
•Poisons – arsenic, cyanide, or mercuric salts
•Insecticides and Herbicides
•Air pollutant – carbon monoxide
•Occupational hazard – asbestos
•Alcohol and Narcotic drugs
Causes of Cell InjuryCauses of Cell Injury
Infectious Agents
•Parasites
•Fungi
•Bacteria
•Rickettsiae
•Viruses
Causes of Cell InjuryCauses of Cell Injury
Immunologic Reactions
•Anaphylactic reaction to foreign protein or drug
•Reactions to endogenous self-antigens – autoimmune diseases
Causes of Cell InjuryCauses of Cell Injury
Genetics Derangements
•Congenital malformation – Down syndrome
•Decreased life of red blood cell – Thalassemia, Sickle cell anemia
•Inborn errors of metabolism
Causes of Cell InjuryCauses of Cell Injury
Nutritional Imbalances
•Protein-calorie deficiencies
•Vitamin deficiencies
•Anorexia nervosa
•Excesses of lipids – Obesity, Atherosclerosis
•Metabolic diseases – Diabetes
Causes of Cell InjuryCauses of Cell Injury
Mechanisms of Cell Injury
•Depletion of ATP•Mitochondrial Damage
•Influx of Intracellular Calcium and Loss of Calcium Homeostasis
•Accumulation of Oxygen-Derived free radical (Oxidative stress)
•Defects in Membrane Permeability
Na+
K+
Ca2+
Mechanisms of Cell InjuryMechanisms of Cell Injury
Depletion of ATP
Mitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury
CausesCauses
Hypoxia, Toxins
Cytosolic Ca2+
Oxidative stress
Lipid breakdown product
Mitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury
• Mitochondrial permeability transition of inner membrane (formation of high-conductance high-conductance channelchannel)
• Leakage of Cytochrome cCytochrome c into cytosol
ATP productionATP production
Mitochondrial Oxidative Phosphorylation
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mitochondrial Damage
Influx of Intracellular Calcium and Loss of Calcium
Homeostasis
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mechanisms of Cell InjuryMechanisms of Cell Injury
Morphology of Cell Injury and Necrosis
•Cell Injury – Reversible
– Irreversible
•Cell Death – Necrosis
– Apoptosis
Morphology of Cell Injury
•Plasma membrane alteration
•Mitochondrial Changes
•Dilation of Endoplasmic reticulum
•Nuclear Alteration
Reversible InjuryReversible InjuryCellular swelling
Fatty change
Morphology of Necrotic Cells
•Increased Eosinophilia - loss of RNA (basophilia)
- denatured cytoplasmic protein•Nuclear Changes
- Pyknosis - Karyorrhexis
- Karyolysis• Myelin figure
– large, whorled phospholipid mass (phospholipid precipitate)
HISTOLOGIC FEATURES OF HISTOLOGIC FEATURES OF COAGULATIVE NECROSISCOAGULATIVE NECROSIS
Normal cellNormal cell
Reversible Reversible cell injurycell injury with with cytoplasmic & cytoplasmic & organelle organelle swelling, swelling, blebbing & blebbing & ribosome ribosome detachmentdetachment
Irreversible Irreversible cell injurycell injury with rupture of with rupture of membrane & membrane & organelles, & organelles, & nuclear nuclear
pyknosispyknosis
KaryorrhexisKaryorrhexis
KaryolysisKaryolysis
Morphologic pattern of Necrotic Cell mass
•Coagulative necrosis
•Liquefactive necrosis
•Caseous necrosis
•Fat necrosis
• Coagulative Necrosis
: intracellular acidosis
– protein denatured
– proteolysis inhibited
Morphologic pattern of Necrotic Cell mass
Ischemic necrosis of the myocardium
A, Normal myocardium.
B, Myocardium with coagulation necrosis
•Liquefactive Necrosis
: focal bacterial (or fungal) infections
– accumulation of inflammatory
cells
: hypoxic death of cells within CNS
Morphologic pattern of Necrotic Cell mass
Coagulative and liquefactive necrosisA, Kidney infarct exhibiting coagulative necrosis
B, A focus of liquefactive necrosis in the kidney
•Caseous necrosis
:gross appearance
: microscopic – granulomatous inflammation
Morphologic Pattern of Necrotic Cell Mass
A tuberculous lung with a large area of caseous necrosis
Foci of fat necrosisfat necrosis with saponification in the mesentery
Explain the difference(s) between reversiblereversible and irreversibleirreversible cell injury.
REVERSIBLE IRREVERSIBLE
Loss of ATP Irreversible mitochondrial damage Phospholipid breakdown Massive peroxidation due to due to PLPase activation uncontrolled chain reaction Depolymerization of actin Cleavage of CSK proteins by proteases
Increase in ROS Uncontrolled ROS; inflammation
Release of calcium from Uncontrolled calcium influxstorage site
Altered metabolism Loss of amino acids
Explain the difference(s) between reversiblereversible and irreversibleirreversible cell injury.
REVERSIBLE IRREVERSIBLE
Loss of ATP Irreversible mitochondrial damage Phospholipid breakdown Massive peroxidation due to due to PLPase activation uncontrolled chain reaction Depolymerization of actin Cleavage of CSK proteins by proteases
Increase in ROS Uncontrolled ROS; inflammation
Release of calcium from Uncontrolled calcium influxstorage site
Altered metabolism Loss of amino acids
Describe Patterns of Necrosis in Tissues or Organs
As a result of cell death the tissues or organs display certain macroscopic changes:
1. CoagulativeCoagulative necrosis
outline of the dead cells is maintained and the tissue is somewhat firm. Example: myocardial infarction
3. CaseousCaseous necrosis
form of coagulative necrosis (cheese-like)
Example: tuberculosis lesions
4. FatFat necrosis
enzymatic digestion of fat
example: necrosis of fat by pancreatic enzymes.
5. GangrenousGangrenous necrosis
Necrosis (secondary to ischemia) usually with superimposed infection
example: necrosis of distal limbs, usually foot and toes in diabetes
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