Pathophysiology Lecture 1 PDF

3th year Pathophysiology lecture 1 1st semester Introduction to pathophysiology and cell injury Lect. Ehab Hamed Abdul-Mageed AL-Kunooze University-College of Pharmacy What the pathophysiology is Pathophysiologia pathos = disease, pain, suffering Physiologia f...

3th year Pathophysiology lecture 1 1st semester Introduction to pathophysiology and cell injury Lect. Ehab Hamed Abdul-Mageed AL-Kunooze University-College of Pharmacy What the pathophysiology is Pathophysiologia pathos = disease, pain, suffering Physiologia fysis = nature; logos = science fysis = nature; logos = science Pathophysiology - definitions is the study of the functional changes associated with a specific disease and seeks to provide an understanding of the mechanisms of disease and how and why alterations in body structure and function lead to the signs and symptoms of disease. Why pathophysiology is important for medical students and physicians 1- Pathophysiology is the bridge between basic science and clinical studies. Its important for patient care, from diagnostic testing and treatment advice to preventing disease. 2- If doctors are able to understand the causes and mechanisms of the disease. Pathology is a result of disease and changes in homeostasis. Homeostasis the human body strives to maintain internal stability, the process of maintaining normal balance within the body is called homeostasis. Pathophysiology the study of abnormal functions in the body and how disease processes work. The disease is an abnormal alteration of structure and/or function in any part of the human body. When a disease is diagnosed, treatment is given to prevent or ameliorate complications. What are the aspects of the disease? 1- Etiology 2- Pathogenesis biological mechanism that leads to the diseased state. Also, the term can describe the origin and development of the disease. 3- Manifestation include signs and symptoms. 4- Prognosis is a prediction of the course of a disease following its onset. It refers to the possible outcomes of a disease (e.g. death, chance of recovery and recurrence). 5- Complications a secondary disease that develops in the course of a primary disease and arises either as a result of it or from independent causes. Types of pathological specimens 1-Autopsy is a dissection performed on a cadaver to find possible cause(s) of death. 2-Biopsy is the removal and examination of a sample of tissue from a living body for diagnostic purposes. There are different types of biopsy and their performed depend on location, size and clinical impression of the lesion. Basic types of Biopsy 1-Incisional biopsy is a medical test to remove a piece of tissue from a lesion or mass. 2-Excisional biopsy is a medical test in which the whole lesion or mass is removed and tested. Structure of pathophysiology 1-General Pathology: is the study of cellular responses to different abnormal stimuli generated and it focuses on the etiology, manifestation and diagnosis of disease e.g. inflammation, fever, shock, stress, edema and cancer…etc 2-Systemic pathology: is the study of diseases as they occur within a particular organ system e.g. GIT and respiratory system…etc CELL INJURY When the cell is exposed to an injurious agent/stress/stimulus, and it leads to injury of the cell, it is termed cell injury. Cell injury is reversible up to a certain point, but if the stimulus persists or is severe from the start, the cell reaches a point of no return and suffers irreversible cell injury and ultimately cell death. Cell death is death of a cell as a result of cell injury. There are two principal patterns of cell death, necrosis and apoptosis. CELL DEATH Necrosis is the type of cell death that occurs due to disease, injury, or failure of the blood supply (ischemia) and it is always pathologic. Apoptosis occurs when a cell dies through activation of an internally programmed death of single cell. Types of cell injury Types of cell injury Types of cell injury Causes of cell injury Cell injury can be caused by a number of agents, including physical agents, chemicals, biologic agents and nutritional factors. Causes of injury (are the same for both reversible and irreversible ) 1) Hypoxia and ATP depletion. It is a common cause of cell injury and cell death. Hypoxia can be due to: Causes of cell injury 2)Physical agents e.g. mechanical trauma, burns and deep cold, sudden changes in atmospheric pressure, radiation, and electric shock 3)Chemical agents and drugs e.g. oxygen in high concentrations, poisons, pollutants, insecticides, industrial and occupational hazards, alcohol and narcotic drugs and therapeutic drugs. 4)Infectious agents 5) Immunologic agents e.g. thyroid damage caused by autoantibodies. 6) Genetic derangements e.g. sickle cell anemia. 7) Nutritional imbalances Factors affecting cell injury Response of the cell to injury depends on: 1. Severity of the injury. 2. Duration of the injury. 3. The type of cell. For example: low dose of toxins or a brief duration of ischemia cause reversible cell injury. While larger toxin doses or longer ischemic duration result in irreversible injury and cell death Mechanism of cell injury 1- Depletion of ATP. 2- Cell membrane damage/defects in membrane permeability:. 3- Mitochondrial damage: It is seen specially in hypoxic injury and cyanide poisoning. 4- Ribosomal damage: It is seen in alcohol damage of liver cells and with antibiotic use. 5- Nuclear and DNA damage. 6- Influx of intracellular calcium leading to loss of normal calcium balance: ischemia causes an increase in intracellular calcium concentration. Increased Ca2+ in turn activates a number of enzymes which cause damage. 6- Free radical injury. Mechanism of cell injury Reversible cell injury Cell injury can be reversible or irreversible. The type of injury, the time duration of injury and the severity of injury will determine the extent of cell damage i.e. whether the injury is reversible or irreversible. Reversible Cell Injury: initially cell injury is reversible. If the injurious stimulus is removed the damage can be reversed. Ultrastructural (electron microscopic) changes associated with reversible cell injury are: 1-Swelling & vacuolization of cytoplasm called “hydropic/ vacuolar degeneration”. 2-Mild mitochondrial swelling 3-Mild rough endoplasmic reticulum and plasma membrane damage. 4-Defect in protein synthesis. 5-Mild eosinophilia of cytoplasm (due to decrease in cytoplasmic RNA) Type of reversible cell injury Cellular swelling 1-Cellular swelling: Mildest and commonest reversible cell injury characterized by swelling of the cell and its organelles. Swelling of cells results from influx of water. Pathogenesis of cellular swelling:- The injurious agents such as hypoxia causes:- 1- Mitochondrial damage. 2- Loss of ATP formation. 3- Failure of the active cell membrane transports (Na+/ K+ ATPase membrane pump). 4- Na enters the cell. 5-K out of cell. 6- Excessive intracellular Na is followed by accumulation of water inside the cell. Cellular swelling 2-Fatty changes 2-Fatty changes are linked to intracellular accumulation of fat. When fatty changes occur, small vacuoles of fat spread throughout the cytoplasm. It results when toxic injury disrupts metabolic pathways and leads to rapid accumulation of triglyceride-filled lipid vacuoles. The liver, where most fats are synthesized and metabolized, is particularly susceptible to fatty change (steatosis) but fatty changes may also occur in the kidney, the heart, and other organs. Fatty changes (steatosis) Irreversible cell injury Irreversible cell injury When cells are injured by sever injurious agents they will die. There are two principal types of cell death:- A- Necrosis. B- Apoptosis. These two types of cell death differ in their mechanisms, morphology, and roles in physiology and disease.  Necrosis Definition of necrosis: refers to un-programmed death of group of cells in an organ or tissue within a living body. Necrosis is a pathologic process that is characterized by denaturation of cellular proteins, leakage of cellular contents through damaged membranes, local inflammation, and enzymatic digestion of the lethally injured cell. Necrosis is characterized by changes in the cytoplasm and nuclei of the injured cell. These changes often are not visible, even under the microscope, for hours after cell death. 1- Cytoplasmic changes. 2- Nuclear changes. Types of necrosis Types of necrosis 1- Coagulative necrosis: This type of necrosis is characteristic of hypoxic injury and is seen in infarcted areas. Infarction (i.e., tissue death) occurs when an artery supplying an organ or part of the body becomes occluded and no other source of blood supply exists. This type of necrosis occurs in kidney (renal infraction) and heart (myocardial infarction). Types of necrosis 2- Liquefactive necrosis: The dead cells are completely digested, transforming the tissue into a viscous liquid that is eventually removed by phagocytes. Examples of liquefaction necrosis are the softening of the center of an abscess and in the brain infarction. Types of necrosis 3-Caseous necrosis: the dead cells appear as cheese like debris. Unlike coagulative necrosis, the tissue architecture of gaseous necrosis is completely obliterated and cellular outlines cannot be distinguished. This type of necrosis occurs in tuberculous infection. Types of necrosis 4- Gangrenous: is the death of tissue due to lost blood supply or infection. There are several types of gangrene each with different causes. 1. Dry gangrene. 2. Moist (wet) gangrene. 3. Gas gangrene. Apoptosis Apoptosis: it is programmed death of single cell. Causes of Apoptosis: physiological and pathological processes. Apoptosis is a highly selective process that eliminates injured and aged cells thereby controlling tissue regeneration. In apoptosis, the cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins. Causes of apoptosis  Causes of apoptosis Apoptosis is responsible for several normal physiologic and pathologic processes. 1- Physiologic processes: A. During embryonic development: e.g. the heart begins as a pulsating tube and is gradually modified to become a fourchambered pump, apoptotic cell death allows for the next stage of organ development. It also separates the webbed fingers and toes of the developing embryo. After puberty, the thymus gland slowly starts to decrease in size by apoptosis. B. Hormone-dependent involution of tissues: e.g. endometrial cells during the menstrual cycle and in the regression of breast tissue after weaning from breast-feeding. Causes of apoptosis 2- Pathologic processes: 1-Apoptosis contributes to carcinogenesis. 2-Apoptosis is involved in the cell death associated with viral infections, such as hepatitis B and C. 3- Apoptosis may also be implicated in neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS), Alzheimer disease, and Parkinson disease. However, the exact mechanisms involved in these diseases remains under investigation. Apoptosis vs Necrosis References -Robbins Basic Pathology 9th edition. - Carol Mattson Porth - Essentials of Pathophysiology 4rd edition.