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what is pathology
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."

slide2
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
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
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.

causes of cell injury
Causes of Cell Injury
  • Oxygen Deprivation
  • Physical Agents
  • Chemical Agents and Drugs
  • Infectious Agents
  • Immunologic Reactions
  • Genetic Derangements
  • Nutritional Imbalances
oxygen deprivation
Causes of Cell InjuryOxygen Deprivation
  • Hypoxia – deficiency of oxygen
  • Ischemia – loss of blood supply(arterial flow or reduced venous drainage)
physical agents
Causes of Cell InjuryPhysical Agents
  • Mechanical trauma
  • Extremes of temperature – burns, deep cold
  • Radiation
  • Electric shock
chemical agents and drugs
Causes of Cell InjuryChemical 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
infectious agents
Causes of Cell InjuryInfectious Agents
  • Parasites
  • Fungi
  • Bacteria
  • Rickettsiae
  • Viruses
immunologic reactions
Causes of Cell InjuryImmunologic Reactions
  • Anaphylactic reaction to foreign protein or drug
  • Reactions to endogenous self-antigens – autoimmune diseases
genetics derangements
Causes of Cell InjuryGenetics Derangements
  • Congenital malformation – Down syndrome
  • Decreased life of red blood cell – Thalassemia, Sickle cell anemia
  • Inborn errors of metabolism
nutritional imbalances
Causes of Cell InjuryNutritional Imbalances
  • Protein-calorie deficiencies
  • Vitamin deficiencies
  • Anorexia nervosa
  • Excesses of lipids – Obesity, Atherosclerosis
  • Metabolic diseases– Diabetes
mechanisms 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
slide15
Na+

K+

Ca2+

Mechanisms of Cell Injury

Depletion of ATP

mitochondrial damage
Mechanisms of Cell InjuryMitochondrial Damage

Causes

Hypoxia, Toxins

Cytosolic Ca2+

Oxidative stress

Lipid breakdown product

mitochondrial damage1
Mechanisms of Cell InjuryMitochondrial Damage
  • Mitochondrial permeability transition of inner membrane (formation of high-conductance channel)
  • Leakage of Cytochrome c into cytosol

Mitochondrial Oxidative Phosphorylation

ATP production

slide18
Mechanisms of Cell Injury

Mitochondrial Damage

morphology of cell injury and necrosis
Morphology of Cell Injury and Necrosis
  • Cell Injury – Reversible

– Irreversible

  • Cell Death – Necrosis

– Apoptosis

morphology of cell injury
Morphology of Cell Injury

Reversible Injury

  • Plasma membrane alteration
  • Mitochondrial Changes
  • Dilation of Endoplasmic reticulum
  • Nuclear Alteration

Cellular swelling

Fatty change

morphology of necrotic cells
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)

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HISTOLOGIC FEATURES OF COAGULATIVE NECROSIS

Karyorrhexis

Normal cell

Reversible cell injury with cytoplasmic & organelle swelling, blebbing & ribosome detachment

Irreversible cell injury with rupture of membrane & organelles, & nuclear pyknosis

Karyolysis

morphologic pattern of necrotic cell mass
Morphologic pattern of Necrotic Cell mass
  • Coagulative necrosis
  • Liquefactive necrosis
  • Caseous necrosis
  • Fat necrosis
morphologic pattern of necrotic cell mass1
Morphologic pattern of Necrotic Cell mass
  • Coagulative Necrosis

:intracellular acidosis

– protein denatured

– proteolysis inhibited

slide28
Ischemic necrosis of the myocardium

A, Normal myocardium.

B, Myocardium with coagulation necrosis

morphologic pattern of necrotic cell mass2
Morphologic pattern of Necrotic Cell mass
  • Liquefactive Necrosis

:focal bacterial (or fungal) infections

– accumulation of inflammatory

cells

:hypoxic death of cells within CNS

slide30
Coagulative and liquefactive necrosis

A, Kidney infarct exhibiting coagulative necrosis

B, A focus of liquefactive necrosis in the kidney

morphologic pattern of necrotic cell mass3
Morphologic Pattern of Necrotic Cell Mass
  • Caseous necrosis

:gross appearance

:microscopic – granulomatous inflammation

slide34
Explain the difference(s) between reversible and irreversible cell injury.

REVERSIBLE IRREVERSIBLE

Loss of ATP  Irreversible mitochondrial damage

Phospholipid breakdown Massive peroxidation due todue 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 influx

storage site  

Altered metabolism  Loss of amino acids

slide35
Describe Patterns of Necrosis in Tissues or OrgansAs a result of cell death the tissues or organs display certain macroscopic changes:1. Coagulative necrosis

outline of the dead cells is maintained and the tissue is somewhat firm. Example: myocardial infarction 

slide38
3. Caseous necrosis

form of coagulative necrosis (cheese- like)

Example: tuberculosis lesions

slide39
4. Fat necrosis

enzymatic digestion of fat

example: necrosis of fat by pancreatic enzymes.

slide40
5. Gangrenous necrosis

Necrosis (secondary to ischemia) usually with superimposed infection

example: necrosis of distal limbs, usually foot and toes in diabetes

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