D2 Cell Adaptations & Cell Injury Lecture Notes PDF

Cellular adaptations and Cell Injury: Introduction, Etiology and Types Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students must know 1. Cellular responses...

Cellular adaptations and Cell Injury: Introduction, Etiology and Types Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students must know 1. Cellular responses to stress and noxious stimuli 2. Cellular adaptations 3. Cell injury and its types 2 Cellular responses to stress and injurious stimuli 3 Cellular Adaptations An increase, decrease or changes in stress on organ can result in Cellular Adaptations ‘’Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment.’’ Physiologic adaptations: usually represent responses of cells to normal stimulation by hormones or endogenous chemical mediators. Pathologic adaptations: are responses to stress that allow cells to modulate their structure and function and thus escape injury. 4 Types of Cellular Adaptations The types of cellular adaptation include: 1. Hypertrophy. 2. Hyperplasia. 3. Atrophy. 4. Metaplasia. 5  1. Hypertrophy: Refers to ↑ Cell Size. Basic description: Hypertrophy is an increase in the size of cells → resulting in Hypertrophy increase in the size of the organ or tissue. Increase in Size of Cells  Characteristics of Hypertrophy Increase in size of cells/ increase in organ size. No new cells/ just bigger cells. Mechanism: Increase in the synthesis of more structural proteins and organelles, and genes activation. Affects cells incapable of proliferation (e.g., cells in cardiac muscle, skeletal muscle and nerve). Hypertrophy and hyperplasia can also occur together (e.g., uterus in pregnancy). Can be physiologic or pathologic.  Physiologic Hypertrophy Physiologic hypertrophy caused by: Increased functional demand (e.g., hypertrophy of skeletal muscles in body builders). Specific hormonal stimulation (e.g.,hypertrophy of uterus or breast enlargement during pregnancy) Pathological Hypertrophy Pathologic hypertrophy caused by increased functional demand Hypertrophy of cardiac muscle cells Example: Left Ventricle Hypertrophy (LVH) following Systemic Hypertension Normal and gravid uterus C  Hypertrophic cardiomyopathy occurs if heart Enlargement of cardiac muscle in muscle cells enlarge and cause response to valve disease the walls of the ventricles (usually the left ventricle) to thicken.  2. Hyperplasia: Refers to ↑ Cell Number. Basic description: Hyperplasia is an increase in the number of cells → resulting in increase the size of the organ or tissue. Hyperplasia It is usually caused by hormonal stimulation. Increase in Number of Cells Mechanism of Hyperplasia 1. Growth Factor Driven → Proliferation of mature cells. 2. Stem Cell Driven → increased output of new cells from tissue stem cells  Characteristics of Hyperplasia A. Increase in number of cells in organ or tissue → increased mass of the organ or tissue. B. Involves the production of new cells from stem cells. C. Affects cells capable of dividing and replication. D. Hyperplasia and hypertrophy generally occur together (e.g., uterus in pregnancy). E. May be triggered by the same external stimuli F. Can be physiologic or pathologic.  Physiologic Hyperplasia There are two types of physiologic hyperplasia are: Hormonal hyperplasia: Proliferation of the glandular epithelium of the female breast at puberty and during pregnancy, after estrogen stimulation. Compensatory hyperplasia: Increases tissue mass after damage or partial resection such as Hyperplasia of liver after partial hepatecotomy.  Pathologic Hyperplasia Pathologic hyperplasia commonly caused by an excessive action of hormones and growth factors acting on target cells Hyperplasia of endometrium due to excess estrogen. Benign prostatic hyperplasia due to excess of androgens. Skin warts (papilloma virus) due to excess of growth factors.  3. Atrophy: Refers to ↓ Cell Size and/or Cell No. Basic description: Atrophy is a decrease in size or in number of cells → lead to decreased size of the organ or tissue. It can be physiologic and pathologic. Atrophy Mechanism of Atrophy Decrease in Size or Number of Cells Atrophy results primarily from decreased protein synthesis due to decreased metabolic activity, and increased proteolysis in cells. Physiological Atrophy Examples Fetal Organs – like the thymus gland and thyroglossal duct. Loss of endocrine stimulation - Endometrium, vaginal epithelium, and breast atrophy after menopause when lost the estrogen stimulation. Senile atrophy: of Brain and Heart.  Pathologic Atrophy The common causes of pathologic atrophy are the following: 1. Decreased workload (Atrophy of disuse) – e.g., immobilization of a limb to permit healing of a fracture. 2. Loss of innervation (Denervation atrophy) - lack of nerve stimulation in peripheral muscles caused by injury to motor nerves. 3. Diminished blood supply (Ischemia atrophy) - e.g., atherosclerosis and arterial occlusive disease. 4. Inadequate nutrition 5. Pressure atrophy– this occurs in areas surrounding the tumours.  4. Metaplasia: Replacement/change of Cell Type → by another Cell Type. Basic description: Metaplasia is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type. Metaplasia. Causes: (Greek: Change. Changes in environment. formation) Change or replacement Irritation of inflammation. of cell type. Nutrition. Mechanism: Reprogramming of local tissue stem cells or, alternatively, colonization by differentiated cell populations from adjacent sites  Types of Metaplasia A. Epithelial Metaplasia Squamous Metaplasia (Columnar → Squamous) - Respiratory tract – due to smoking/ vitamin A deficiency. - Excretory duct of gland – due to stones. Columnar Metaplasia (Squamous→ Columnar) - Esophagus (Barrett's Esophagus) – Chronic acid reflux. Note, Cancer may arise. B. Mesenchymal (Connective Tissue) Metaplasia Osseous metaplasia (Muscle → Bone) - Myositis ossificans - occasionally occurs after bone fracture.  Examples of Metaplasia Changes to Site Stimuli Native Epithelium (Metaplastic Epithelium) Respiratory Tract Smoking Columnar Squamous Excretory Ducts of Salivary Glands, Calculi Columnar Squamous Pancreas or bile ducts Lower Esophagus Chronic acid reflux Squamous Columnar Fracture Site Muscle Injury, truma Muscle Bone Summary of Cellular Adaptations Hyperplasia Hypertrophy Atrophy Metaplasia. Increase in Increase in Decrease in Size or Change or replacement Number of Cells Size of Cells Number of Cells of cell type. Cell injury Most forms of diseases begin with cell injury followed by consequent loss of cellular function. Cell injury is defined as the effect of a variety of stresses due to etiologic agents a cell encounters resulting in changes in its internal and external environment The cellular response to stress may vary and depends upon following two variables: i) Host factors i.e. the type of cell and tissue involved. ii) Factors pertaining to injurious agent i.e. extent and type of cell injury. 22 ETIOLOGY OF CELL INJURY 1. Hypoxia and ischaemia 2. Physical agents 3. Chemical agents and drugs 4. Microbial agents 5. Immunologic agents 6. Nutritional derangements 7. Ageing 8. Psychogenic diseases 9. Iatrogenic factors 10. Idiopathic diseases 11. Genetic causes 23 ETIOLOGY OF CELL INJURY HYPOXIA AND ISCHAEMIA Cells essentially require oxygen to generate energy and perform metabolic functions. Deficiency of oxygen or hypoxia results in failure to carry out these activities by the cells. Hypoxia is the most common cause of cell injury. 24 Cell Injury : Types Reversible cell injury Irreversible cell injury 25 Cell injury: Types Reversible cell injury is characterized by functional and structural alterations in early stages or mild forms of injury, which are correctable if the damaging stimulus is removed. Within limits, the cell can repair the alterations seen in reversible injury and if the injurious stimulus abates, may return to normalcy. 27 Irreversible injury and Cell Death Persistent or excessive injury, however, causes cells to pass the rather nebulous “point of no return” into irreversible injury and cell death. Different injurious stimuli can induce cell death Mainly 2 types of mechanisms or types of cell death 1. Necrosis 2. Apoptosis 28  References 1. Robbins and Cotran Pathologic Basis of Disease; 10th ed. 2021 2. HarshMohan Textbook of Pathology. 7th edition. 33  Thank You Any questions? [email protected] 34