Introduction to Pathology Lecture 2: Cell Response to Injury PDF

 Introduction to Pathology MDL 338 Prof. Dr. INTRODUCTION Noha Mohammed Afifi TO  Assignment for “Introduction to Pathology” 1- Role of Physiotherapy in management of Osteomyelitis. 2- Types & Healing of Skin Wounds: Rol...

 Introduction to Pathology MDL 338 Prof. Dr. INTRODUCTION Noha Mohammed Afifi TO  Assignment for “Introduction to Pathology” 1- Role of Physiotherapy in management of Osteomyelitis. 2- Types & Healing of Skin Wounds: Role of Physiotherapy. 3- Pathological causes of Hyperplasia: Role of Physiotherapy in treatment. 4- Hypersensitivity disorders (Anaphylaxis) 5- Healing of Nerve injuries in PNS & CNS: Role of Physiotherapy. 6- Healing of Bone Fractures: Role of Physiotherapy. 7- Cell Aging. 8- Phlegmonatous Inflammation: Role of Physiotherapy. 9- Steatosis (Fatty Liver). 10- Sheehan Syndrome.  Lecture 2 Cell Response to Injury  Causes of Cell Injury) Cell injury can be caused by either: A- Hypoxia and Ischemia (the most important cause of cell injury). B- Genetic factors. C- Acquired (Environmental) factors. D- Aging.  (A) Hypoxia and Ischemia Hypoxia means Oxygen deficiency Ischemia means reduced blood in Tissues. supply. Both deprive tissues of Oxygen. In addition, Ischemia results in deficiency of essential Nutrients and accumulation of Toxic metabolites  What are the Causes of HYPOXIA? Hypoxia (decrease of oxygen supply to the Tissues) is the most important cause of cellular injury]. Causes of HYPOXIA: 1- Ischemia: Reduction or loss of blood supply [such as in case of arterial thrombosis]. 2- Inadequate Oxygenation of Blood e.g. in cases of Cardio-Respiratory Failure. 3- Loss of Oxygen-Carrying Capacity of the Blood as in cases of Anemia (reduced RBCs number------reduced Hb).  Examples of Ischemia a) Thrombosis of Coronary artery b) Thrombosis of Cerebral artery results in Myocardial results in Brain Ischemia. Ischemia.  Homework 1: - Complete: a) Hypoxia means------------------ b) Ischemia means ----------------. Give 2 examples for Ischemia. c) Inadequate oxygenation of blood occurs in --------------------------. d) Loss of oxygen carrying capacity of the blood occurs in ---------------.  (B) Genetic Factors - Chromosomal & gene mutations.  (C) Environmental Factors Environmental causes of disease include: ‫االسباب البيئية لالمراض‬ 1) Physical agents. 2) Chemical agents. 3) Nutritional [deficiency or excess]. 4) Infections. 5) Psychogenic factors. 6) Immunological factors.  Environmental Factors 1- Physical agents: Physical agents include: -) Extremes of temperature [heat & cold]. -) Electric shock. -) Trauma [Mechanical due to e.g. motor vehicle crashes]. -) Radiation therapy (Radiotherapy) for cancer (High Dose). -) Ultraviolet Rays.  Environmental Factors i- Drugs ii- Poisons iii- Pollutants 2- Chemical agents: iv- Caustics v- Social (I) ***Therapeutic Drugs as:  Chemotherapy used for cancer treatment: Nephrotoxic.  Paracetamol is Hepatotoxic & Nephrotoxic. (II) Poisons as: Cyanide is toxic to all body cells.  Many Drugs are metabolized in liver & excreted in kidney, so these organs are susceptible to chemical injury.  Environmental Factors 2- Chemical agents: (III) Environmental Pollutants, as:  Asbestos  Mercury (IV) Caustics & Strong Acids: (V) Social Stimuli: act locally at the site of - Alcohol is Hepatotoxic. application. - Narcotics:‫المخدرات‬damage CNS (Neurotoxic) e.g. Morphine, Heroine, Cocaine  Environmental Factors 3- Nutritional Deficiency or Excess: Nutritional Deficiency may take the form of:  Deficiency of the MAJOR classes of food, usually PROTEIN in case of Marasmus or Kwashirkor. or  Deficiency of Vitamins e.g. Vitamin D deficiency causes Rickets in children.  Deficiency of elements essential for metabolic processes e.g. iron for hemoglobin synthesis. Childhood Malnutrition Diseases  Environmental Factors 3- Nutritional Deficiency and Excess: On the other hand, Dietary Excess: Obesity. Has become increasingly common with dangers of: - Type 2 diabetes mellitus. - Hypertension. - Atherosclerosis. - Fatty liver.  Environmental Factors 4- Infections: Viruses, Bacteria, Fungi, Parasites all cause disease.  Environmental Factors ‫العوامل النفسية‬ 5- Psychogenic Factors: Mental stressors particularly in technologically-advanced communities, - Contribute to some diseases.  Environmental Factors 6- Immunological Factors: - The immune system defends the body against microorganisms and parasites. - However, Abnormal immune reactions can result in cell and tissue injury.  - Immunological Factors: ii) Auto- iii) Immuno- i) Hypersensitivity immunity deficiency In All of these situations, immune response elicits Inflammatory Reaction; which is the cause of cell damage.  - Immunological Factors: i) Hypersensitivity - This is exaggerated immune response to an antigen (Allergen) for example: Bronchial Asthma can occur due to exaggerated immune response to the harmless pollen.  - Immunological Factors: ii) Autoimmunity - This is an abnormal immune response against the self-antigens of the host. - Therefore, Autoimmunity is a hypersensitivity reaction against self- antigens. - For example Type 1 Diabetes Mellitus is caused by autoimmune destruction of the beta cells of the Islets of Langerhans of the Pancreas.  - Immunological Factors: iii) Immunodeficiency - This is due to deficiency of a component of the immune system which leads to increased susceptibility to different diseases. - An example is AIDS.  Homework 2: - Complete: a) Physical agents that cause cell injury include -----------, ------------, --------- & ---------- b) -------------- & --------------- are Hepatotoxic. c) Protein deficiency causes childhood malnutrition diseases e.g. ------- & -------------. d) Type I Diabetes Mellitus is a type of abnormal immune response known as ---------. e) ------------ is an example of hypersensitivity immune reaction.  Cell Response to Injury Stressmay force the cell to a new state :- (I) Adaptation: Changes in cell morphology (shape) in response to Stress *e.g. Atrophy, Hypertrophy --- INABILITY To Adapt to Stress Occurs when stress exceeds capacity of the cell to adapt. (II) Cell Injury a) “Reversible “ Cell Injury (Degeneration): NON-LETHAL (MILD / Transient) injury, causes Metabolic and Morphologic changes in the cell that can be corrected if injury is mild or removed. b) “Irreversible” Cell Injury (Cell Death): LETHAL (SEVERE) injury causes Permanent pathologic changes in the cell that results in cell death.  Homework 3: - Complete: a) Changes in cell morphology in response to stress, defines------------------ b) Reversible cell injury is known as -------. It results when the stress is --------- or ------- --------------. c) Irreversible cell injury is caused by ------- injury, that results in cell --------. d) Types of Cell Death include ------- &---------.  Adaptations may be: 1) Physiological Adaptation. 2) Pathological Adaptation. The cell adapts by 1 of 5 processes: 1- Atrophy. 2- Hypertrophy. 3- Hyperplasia. 4- Metaplasia. or 5- Dysplasia.  1- Atrophy ‫ضمور‬ Definition of Atrophy: Reversible Atrophy is Reduction in the size & Weight of an organ, due to reduction in the SIZE of its cells, “and / or” NUMBER of cells, OR BOTH.  - Atrophy ‫ضمور‬ Mechanism of Atrophy: Decreasing the number of organelles in the cell by Autophagy, with resulting increase in the number of Autophagic Vacuoles (seen under microscope)  Causes of Atrophy: A- Physiological. B- Pathological. A- Physiological Atrophy: (occurs mostly with Age) e.g. - Thymic Involution (at puberty) i.e. at a young age. - Appendix at middle age. - Uterus & Ovary in females after menopause due to loss of hormonal stimulation by Estrogen.  Causes of Atrophy: A- Physiological. B- Pathological. A- Physiological Atrophy: (occurs mostly with Age) e.g. - Senile (above the age of 70) atrophy of heart and brain (Alzehimer’s disease). Senile atrophy of the heart of the brain  Exam Gross Appearance of BrainofAtrophy the brain A B A: Normal brain of a young adult. B: Atrophy of the brain in an 82-year-old patient with Atherosclerotic disease. Atrophy of the brain is due to Aging and reduced blood supply (Ischemia). B- Pathological Atrophy: 1- Disuse atrophy 2- Neurogenic atrophy. 3- Ischemic atrophy. 4- Pressure atrophy. 5- Nutritional atrophy.  B- Pathological Atrophy: 1) Disuse Atrophy of Muscle “Use it or Lose it” e.g. Skeletal Muscle e.g. prolonged bed rest (e.g. immobilization by wearing cast for healing of fractures of long bones (decreased workload)  B- Pathological Atrophy: 2) Neurogenic Atrophy of Muscle Peroneal Nerve (branch from Sciatic Nerve) supplies the Tibialis anterior muscle which is responsible for dorsiflexion of the ankle. Injury to the peroneal nerve causes Foot Drop. Loss of nerve supply (due to nerve injury or spinal cord injury), also leads to Disuse Atrophy due to Muscle Paralysis B- Pathological Atrophy: (Ischemic Atrophy of Kidney) Atrophy of Kidney due to decreased blood 3) Ischemic Atrophy supply (Ischemia) Exam Normal Kidney Stenosis = Atrophic Kidney Narrowing Gross appearance of Atrophic Kidney  B- Pathological Atrophy: Exam 4) Pressure Atrophy Aneurysm (focal dilatation) of the abdominal Aorta, causes pressure on the bodies of vertebrae, resulting in atrophy of the bony vertebral bodies due to pressure on blood vessels, while cartilaginous discs are Not affected (Cartilage is Avascular). Aneurysm of the abdominal aorta (white arrow) resulting in pressure atrophy of vertebral bodies.  B- Pathological Atrophy: 5) Nutritional Atrophy mainly due to Protein deficiency (e.g. Marasmus & Kwashiorkor) [muscle atrophy in children due to protein deprivation].  B- Pathological Atrophy: 6) Endocrine Atrophy A Destructive lesion affecting the Pituitary gland (Hypopituitarism) with loss of Hormones ------ leads to Atrophy of: - Thyroid gland (TSH), - Adrenal glands (ACTH), and - Gonads (Testis & Ovary) (FSH and LH)  Homework 4: a) List 4 Causes for Physiological Atrophy. b) List 5 Causes for Pathological Atrophy. 46 2- Hypertrophy ‫تضخم نتيجة زيادة حجم الخاليا‬ Definition of Hypertrophy: Reversible Hypertrophy is an increase in the SIZE of the organ, due to increase in the SIZE of its cells, Without an increase in the Number of cells (i.e. No New cells, just bigger cells). Hypertrophy occurs when cells have limited capacity to divide.  - Hypertrophy ‫تضخم نتيجة زيادة حجم الخاليا‬ Mechanism of Hypertrophy: (due to increase in the number of organelles). Causes of Hypertrophy: Hypertrophy can be Physiological or Pathological and is caused by either:  Increased workload  Hormonal stimulation.  Growth factors.  Causes of Hypertrophy: A- Physiological. A- Physiological Hypertrophy: B- Pathological. - Enlargement of skeletal muscle due to Exercise (increased workload) in Athletes. - Pregnant (gravid) uterus [increased mechanical load on uterine smooth muscle by the growing fetus, under Estrogen stimulation]. Gross Picture of Hypertrophic Gravid (Pregnant) Uterus Exam Gravid Uterus Normal Uterus B- Pathological Hypertrophy: - i) Cardiac: Left ventricular hypertrophy in case of Systemic Hypertension (due to increased load against the heart) ….end in Heart Failure. - ii) Compensatory: In Paired organs e.g. in case of Unilateral Nephrectomy so the other kidney undergoes Hypertrophy. B- Pathological Hypertrophy: - iii) Hormonal Hypertrophy: due to Pituitary Tumor secreting excess Growth Hormone, causing Gigantism in Childhood (before closure of Epiphyseal plates of bone so becomes very tall) and Acromegaly in Adulthood. Height is Not affected Gigantism in Child Acromegaly in Adult  Gross Appearance of Exam  Homework 5: Hypertrophy is defined as ………….. a) Mention 2 Examples for Physiological Hypertrophy. b) Mention 2 Examples for Pathological Hypertrophy. 54  3- Hyperplasia ‫تضخم نتيجة زيادة عدد الخاليا‬ Definition of Hyperplasia: Reversible Hyperplasia is increase of tissue mass due to increase in the NUMBER of cells. This occurs in response to HORMONES & growth factors. Occurs in tissues whose cells can divide, [so increase their number] or contains many stem cells. Causes of Hyperplasia: A- Physiological Hyperplasia; A- Physiological. B- Pathological. 2 Types 1- Hormonal Hyperplasia e.g. Hyperplasia of female Mammary e.g. Hyperplasia of gland (Breast) at Puberty, during Uterus during Pregnancy &Lactation Pregnancy (under the (under the effect of effect of Estrogen) Estrogen) Causes of Hyperplasia: A- Physiological Hyperplasia; A- Physiological. B- Pathological. 2 Types 2- Compensatory Hyperplasia e.g. when lobe of liver is resected, mitotic activity in the remaining cells begins as early as 12 hours, then restoring the liver to its normal size (under the effect of Growth factors produced by uninjured hepatocytes). Then, Growth Inhibitors turn off cell proliferation.  Homework 6: Hyperplasia is defined as ………….. a) Mention 2 Examples for Physiological Hormonal Hyperplasia. b) Complete: Physiological Compensatory Hyperplasia is seen in case of ……………………… 58  B- Pathological Hyperplasia; 4 Types 1- Hormonal Stimulation: – In females, Excess Estrogen (without antagonizing Progesterone) acts on Breast causing [FIBRO-Cystic disease of the breast, was called: Mammary Hyperplasia] [Precancerous lesion]. FibroCystic disease of breast [Precancerous Lesion] if the cause remains  B- Pathological Hyperplasia; 4 Types 1- Hormonal Stimulation: - In females, Excess Estrogen in Uterus-----Endometrial Hyperplasia which is a common cause of abnormal uterine bleeding. - Endometrial Hyperplasia may be [Precancerous lesion if the cause remains]. [Precancerous lesion if the cause remains]. Post- Menopausal Females receiving Hormone Replacement Therapy (HRT)  B- Pathological Hyperplasia; 4 Types 1- Hormonal Stimulation: - In males: Increased DHT [Not androgen]----- Senile Prostatic Hyperplasia [Not precancerous]. NOT- Precancerous lesion  B- Pathological Hyperplasia; 4 Types 1- Hormonal Stimulation: Exam Increased Pituitary Tumors - Hyperplasia of Thyroid Gland: causing Goitre due to increased TSH. - More in Females. Increased Pituitary Tumors - Hyperplasia of Adrenal Gland: causing Cushing Syndrome due to increased ACTH, results in excess secretion of Cortisol. Goiter (increased TSH); Hormonal Pathological Hyperplasia  B- Pathological Hyperplasia; 4 Types 2- Irritation Hyperplasia: occurs in tissues which have a power of mitosis e.g. epithelial tissue which divide to overcome the irritation] e.g. Irritation of Transitional epithelium of the Urinary Bladder by Bilharziasis Ova, which may progress to Cancer of Urinary Bladder.  B- Pathological Hyperplasia; 4 Types 3- Reactive Hyperplasia e.g. hyperplasia of lymph nodes in infections.  Exam Enlarged Cervical Lymph Node in the neck of a boy, due to infection (Tonsillitis); Reactive Pathological Hyperplasia  B- Pathological Hyperplasia; 4 Types 4- Compensatory Hyperplasia e.g. hyperplasia of Bone Marrow in response to Hemorrhage. Cases of Combined Hypertrophy & Hyperplasia 1- Pregnant (gravid) Uterus. 2- Compensatory: in case of Unilateral Nephrectomy.  Homework 7: a) List 2 Examples for Precancerous Lesions of Pathological Hormonal Hyperplasia in females. b) List 1 Example of Pathological Hormonal Hyperplasia in Males. - C) Pathological Irritation Hyperplasia is seen in cases of………. - d) Pathological Reactive Hyperplasia is seen in cases of………. - e) Combined Hyperplasia and Hypertrophy are seen in cases of ------ - & --------- 68 Hypoplasia: Failure of an organ to reach full maturation, smaller than normal, during Embryogenesis, e.g. Uterine Hypoplasia Normal Uterus Uterine Hypoplasia (Infantile Uterus---Infertility) Aplasia: Failure of an organ to develop during Embryogenesis, e.g. Kidney Aplasia (Agenesis) Kidney Aplasia  4- Metaplasia:  Change of 1 type of Differentiated epithelium into another type that can better endure the change or stress. HOW??  Reprogramming of genes of Stem Cells to differentiate into NEW Cells.  4- Metaplasia: WHY?? Metaplasia is usually a response to Chronic Inflammation or Irritation. Differentiated cells are better able to withstand the stress. Metaplasia is Reversible on removal of the cause. Metaplasia is NEVER Physiological. All cases of Metaplasia are Precancerous. Metaplasia may be the 1st step towards Neoplasia  EXAMPLES; (I) Squamous Metaplasia  1- In Heavy Cigarette Smokers: Replacement of the normal Respiratory epithelium in the upper airway (in Trachea & Bronchi) by squamous epithelium, for better resistance. [change of Pseudo-stratified columnar ciliated epithelium into squamous epithelium] How is Respiratory Metaplasia a “double-edged Sword”? Stratified epithelium is able to withstand the poisons in cigarette smoke; however important protective X mechanisms are lost e.g. mucus secretion & ciliary clearance of foreign body.  EXAMPLE; (I) Squamous Metaplasia  2) In Bilharziasis: Replacement of  3) In Gall Bladder Stones: the normal Transitional epithelium Replacement of the normal in the Urinary bladder by Squamous Columnar epithelium in the Gall Epithelium. bladder by Squamous Epithelium.  EXAMPLE; (II) Columnar Metaplasia - GERD (Reflux Esophagitis) “Barrett’s Esophagitis”. Stratified Squamous Epithelium of Esophagus, changes to (Columnar epithelium of stomach to produce protective mucus). GERD (Gastro-Esophageal Reflux Disease). Barrett’s Esophagus.  Homework 8: a) Metaplasia is defined as ………….. b) Mention 2 Examples for Squamous Metaplasia. c) Mention 1 Example for Columnar Metaplasia. 76  5- Dysplasia; [Abnormality in Morphology & Arrangement] Definition: Dysplasia is: Disordered cell growth, with Partial loss of resemblance to the tissue of origin - Usually induced by Chronic cell irritation. - No Invasion [Not Yet Cancer] morphology Herpes Simplex Virus  Features of Dysplastic Cells: Nuclear Changes  Nuclear Pleomorphism: Nuclei are variable in size and shape (Anisonucleosis). Nuclear Membrane: Irregular. Nuclear Chromatin: Irregular distribution of chromatin, mostly Hyperchromatic (darkly stained - Hyperchromatosis)  Size of Nucleus: Large. + Increased Nuclear-to-Cytoplasmic ratio: (N/C Ratio) [more than the normal 1:4]……… now 1 : 1  Nucleoli: very large size & prominent.  Features of Dysplastic Cells: Cytoplasmic Changes  Cellular Pleomorphism (i.e. Variation in size and shape of cells).  Loss of Polarity: Disorganization of tumor cells. Tumor Giant cells: Multinucleated cells that are much larger than their neighbors.  Disturbed Function: (e.g. reduced keratinization, reduced secretions…)  Features of Dysplastic Cells: Exam Mitoses: Frequent and Abnormal Mitotic Figures; e.g. Tripolar Quadripolar or Multipolar forms. Abnormal Tripolar mitosis Normal: 1 Mitotic Figure  Dysplasia; [Abnormality in Morphology & Arrangement] Microscopic Characteristics: affects mainly Epithelium. Grading of Dysplasia:  Mild Dysplasia (Dysplasia Grade 1) (affecting lower third of epithelium; actively dividing cells).  Moderate Dysplasia (Dysplasia Grade 2) (affecting lower two-third of epithelium). Mild and moderate grades of dysplasia are Reversible on removal of the cause. Examples (Sites) of Dysplasia: - Cervical dysplasia in females with chronic cervicitis.  Severe Dysplasia (involves the Whole epithelial thickness). Severe dysplasia corresponds to Carcinoma in situ (Not invading yet), a highly precancerous, almost all cases progress to invasive cancer (invade).