Download Cell Injury

IN THE NAME OF ALLAH ……….
Cell Injury-1
ADAPTATION OF CELLULAR GROWTH AND
DIFFERENTIATION
Dr. Shoaib Raza
Associate Professor, Pathology, RIHS
OBJECTIVE
• The objectives of this lecture are:
• Introduce the term adaptation and cell injury
• Define and brief explanation of various forms of
adaptation; like
•
•
•
•
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
CELL INJURY
• When the adaptive capabilities of the cell are exceeded, the cell injury
ensues
• Reversible cell injury
• Irreversible cell injury
• Cell death, necrosis or apoptosis
• Causes of cell injury:
• Ischemia
• Chemical agent
• Physical agent
• Nutritional imbalance
• Immunologic mechanism
• Biological agent
• Genetic derangements
• Aging
ADAPTATION
• Adaptations are reversible change in the SIZE, NUMBER,
PHENOTYPE, METABOLIC ACTIVITY or FUNCTIONS of the
cells in response to changes in their environment.
• Such adaptations may take several forms:
• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia
HYPERTROPHY
• Increase in the size of cell resulting in an increase in the size of
organ.
• Seen in non-dividing cells
• Pathologic hypertrophy
• Physiologic hypertrophy
• Causes may include:
• Increased functional demand
• Stimulation by hormone
• Stimulation by growth factors
• Increased work load
CAUSES AND EXAMPLES OF HYPERTROPHY
Cause
Physiologic example
Increased work load
Skeletal muscle hypertrophy in Myocardial hypertrophy, due
athletes and body builders
to hypertension or out flow
obstruction
Stimulation by hormone
Uterus during pregnancy
Stimulation by growth factors
Pathologic example
Prostatic enlargement in old
males
MECHANISM OF HYPERTROPHY
• Result of increased production of cellular proteins
• Increased actions of mechanical sensors triggered by
increased work load
• Growth factors (TGF-β, IGF-1, FGF, etc.)
• Vasoactive agents (Endothelin-1, Angiotensin-II)
• These stimuli work coordinately to increase the
synthesis of muscle protein, responsible for
hypertrophy
MECHANISM OF HYPERTROPHY (CONTINUE)
• Switch of contractile proteins from adult to fetal form
• α-isoform of heavy chain of myosin is replaced by β-isoform
• Reinduction of ANF
• May be a combination of mechanical and chemical
stimuli, leads to genetic and molecular rearrangements
during hypertrophy
SUBCELLULAR ALTERATIONS
• Sometimes a subcellular organelle may undergo hypertrophy
• Endoplasmic reticulum of hepatocytes in barbiturates poisoning
• Mitochondrial hypertrophy (giant mitochondria)
EXAMPLES OF HYPERTROPHY
Physiologic Hypertrophy
Pathologic Hypertrophy
• Breasts at puberty
• Myocardial hypertrophy
• Breasts during pregnancy
• Uterus during pregnancy
• Skeletal muscle hypertrophy
in athletes
• Prolonged hypertension
HYPERPLASIA
• An increase in the number of cells in an organ or tissue, usually
resulting in increased mass of the organ or tissue.
• Seen in the cells which are capable of dividing, and thus
increasing the number of cells
• Usually accompanied by hypertrophy as well
• May be
• Physiologic
• Pathologic
OR
PHYSIOLOGIC HYPERPLASIA
• Can be divided into:
• Hormonal hyperplasia:
• Proliferation of glandular epithelium of female breast at
puberty and during pregnancy
• Compensatory hyperplasia:
• Live liver donors
PATHOLOGIC HYPERPLASIA
• Mostly caused by excessive hormone or growth factors acting
on target cells
• Endometrial hyperplasia
• Benign prostatic hyperplasia
• May be a characteristic response to certain viral infections. e.g.
Human Papilloma Virus
MECHANISM OF HYPERPLASIA
• Is the result of growth factor-driven proliferation of mature cells
• Or in some cases, increased output of new cells from tissue
stem cells
• After some minor hepatic injury, liver cells regenerate, under
influence of certain growth factors
• But if regenerative capacity of hepatocyte is compromised (e.g. in
hepatitis), hepatocyte can instead regenerate from intrahepatic
stem cells
Normal endometrium (Proliferative
phase)
Endometrial Hyperplasia
EXAMPLES OF HYPERPLASIA
Physiologic
Pathologic
• Hyperplasia of breasts at
puberty
• Endometrial hyperplasia
• Hyperplasia of breasts during
pregnancy
• Hyperplasia of endometrium
during proliferative phase of
menstrual cycle
• Hyperplasia of bone marrow
• Prostatic hyperplasia
• Hyperplastic polyps in GIT
• Hyperplasia of thyroid gland in
Grave’s disease
• Stratified squamous
hyperplasia of skin and mucus
membranes in HPV infection
CONSEQUENCES OF HYPERPLASIA
• Increased cell number results in:
• Increased functional capacity
• Increase in the size of organ/tissue
• Increased demand of nutrition and perfusion
• In some cases hyperplasia presents a fertile soil for the
development of cancer (neoplasia)
ATROPHY
• Reduction in the size of cell associated with reduction
in the size of tissue or organ
• Can be
• Physiologic:
• During embryogenesis and metamorphosis
• Uterus after parturition
• Pathologic
CAUSES OF ATROPHY
• Pathologic atrophy:
• Decreased work load (Disuse atrophy)
• Loss of innervation (Denervation atrophy)
• Diminished blood supply (Ischemic atrophy0
• Inadequate nutrition (Marasmus, cachexia)
• Loss of endocrine stimulation
• Pressure
• Physiologic atrophy:
• Senile atrophy
• Hormonal atrophy in breasts or uterus
MECHANISM OF ATROPHY
• Decreased protein synthesis
• Increased protein degradation
• Increased autophagy (self eating)
• Increased number of autophagic vacuoles (brown
atrophy)
METAPLASIA
• One adult (differentiated) cell type is replaced by
another cell type
• Usually reversible
• Almost always pathological
• Columnar to squamous cell (chronic bronchitis)
• Squamous to columnar (Barrett’s esophagus)
• May be preneoplastic condition
ANY QUESTIONS