Transcript 1- Cell and tissue injury

Introduction of
Pathology
By: Dr Tarek Atia
• Pathology is "Scientific study of disease“ Study of
structural and functional changes in disease.
• You need to have a basic knowledge of normal
Anatomy (structure) and Physiology (function) to
understand Pathology.
Diseases is an expression of "discomfort" due to
structural or functional abnormality.
This abnormality can be caused by various agents
Eg. Bacteria, virus, heat, radiation etc. collectively
called 'etiology'.
• Factors causing disease are mainly two types.
Environmental (or external) factors and Genetic
(or Internal) factors.
• Diseases which present since birth are called
Congenital diseases and all other diseases are
known as Acquired diseases.
• Diseases which occur in families are known as
Familial diseases.
Major groups of diseases are Inflammatory, Degenerative
& Neoplastic.
Inflammatory disorders are due to damage to tissues by
various injuries (physical, chemical, infections etc.)
Degenerative disorders are due to lack of growth or
ageing.
Neoplastic disorders are due to excess cell division
forming tumours.
Cell & Tissue Injury
Cell Injury
Damage or alteration of one or more cellular components
1. Many types of injury are tissue-specific because of
anatomic relationships and tissue response to
chemical and infectious agents.
2. Cell injury disrupt cell physiology; so the cell does not
function at full capacity.
Stages in the cellular response to stress and
injurious stimuli
Causes of Cell and Tissue Injury
1. Physical agents
2. Chemicals and drugs
3. Infectious pathogens
4. Immunologic reactions
5. Genetic mutations
6. Nutritional imbalances
7. Hypoxia and Ischemia: cell injury resulting
from inadequate levels of oxygen.
Causes:
A. Inadequate blood supply
B. Lung disease
C. Heart failure
D. Shock
Hypoxia and IschemiaWhy So Important?
All cells in the body require a continuous supply
of oxygen in order to produce ATP via oxidative
phosphorylation in mitochondria.
ATP is absolutely critical for life.
Susceptibility of specific cells to ischemic
injury
• Neurons: 3 to 5 min.
• Myocytes, hepatocytes, renal epithelium: 30 min. to
2 hr.
• Cells of soft tissue, skin, skeletal muscle: many hours
Outcomes from cell injury depend upon:
1. Type of injury
2. Severity of the injury
3. Duration of the injury
4. Type of cell being injured- Some cell types sustain
injury better than others; some tissues (e.g. liver)
have a capacity to regenerate.
Consequences of Injury
1. (Reversible): No long term effects- the cell damage
is repaired, the effects of the injury are reversible.
2. The cell “adapts” to the damaging stimulus.
3. (Irreversible): The cell dies, undergoing necrosis.
The damage is irreversible.
Adaptation to injury
1. Atrophy: decrease in the size and functional capacity
of the cell. after normal growth has been attained . ( O2,
blood, nerve supply)
2. Hypertrophy: an increase in the size of the cell
secondary to an increase in cell function. Increase in
the number of mitochondria and ER, etc.
3. Hyperplasia: an increase in the number of cells of
a tissue in response to a stimulus or injury.
4. Metaplasia: replacement of one type of tissue with
another in response to an injury.
5.
Hypoplasia:
incomplete
development
or
underdevelopment of an organ / tissue (less severe in
degree than aplasia).
6. Aplasia: lack of development of an organ or tissue
(may have a rudimentary organ). can also refer to
lack of production of cells from an organ or tissue (eg
aplastic anemia).
Hypertrophy versus Necrosis
Muscle hypertrophy
Uterine hypertrophy
Metaplasia
Diagram of columnar to squamous metaplasia.
Cell Atrophy
Causes
1.
Loss of blood supply or innervations
2.
Loss of endocrine factors (eg. TSH)
3.
Decrease in the workload
4.
Aging, chronic illness
Reversible Cell Injury
1. Cell swelling– usually accompanies all types of injury.
Results from an increase in water permeability.
Reverses once membrane function is restored
2. Increase in extracellular metabolite-- Because of a
biochemical derangement. i.e.: Increase in extracellular
glycogen in diabetes.
3. Fatty change in liver. Vacuoles of fat accumulate
within the liver cell following many types of injury:
alcohol
intoxication,
chronic
illness,
mellitus, etc.
This may be due to:
•
An increase in entry of free fatty acids.
•
An increase in synthesis of free fatty acids.
•
A decrease in fatty acid oxidation.
diabetes
Vulnerable Sites of the Cell
1.
2.
3.
4.
Cell membranes
Mitochondria
Endoplasmic reticulum
Nucleus
Cell Death
• Apoptosis
• Necrosis
Morphology of Necrosis
Pyknosis
• Shrunken nucleus with dark staining
• Seen in a necrotic (dead) cell
Karyorrhexis
• Fragmentation of pyknotic nucleus
Karyolysis
• Extensive hydrolysis of pyknotic nucleus with
loss of staining
• Represents breakdown of the denatured
chromatin
Karyolysis
Types of Necrosis
1- Coagulative Necrosis
• Dead cells remain as ghost-like remnants of their
former self
• Classically seen in an MI
Cardiac muscle fibers
Kidney (necrotic renal tubules)
2- Liquefactive Necrosis
• The dead cell undergoes extensive autolysis, caused
by the release of lysosomal hydrolases (proteinases,
DNases, RNases, lipases, etc.)
• Seen classically in the spleen and brain following
infarction.
Liquefactive
Necrosis
(A) Coagulative vs. (B) Liquefactive Necrosis
3- Caseous Necrosis (caseum cheesy)
• Resembles cottage cheese
• Soft, friable, whitish-grey
• Present within infected tissues
• Seen in Tuberculosis (Mycobacterium tuberculosis)
Caseous Necrosis
Caseous Necrosis
4- Fat Necrosis
• Leakage of lipases from dead cells attack triglycerides
in surrounding fat tissue and generate free fatty acids
and calcium soaps
• These soaps have a chalky-white appearance
• Seen in the pancreas following acute inflammation