Pathophysiology Unit 1- HOMEOSTASIS Part-I.pptx
- 1. Unit-1 Basic Principles of Cell Injury and Adaption Presented by, Ms. Deshmukh Y.R. Asst. Professor GIPER LIMB SATARA
- 2. SYALLABUS -Intro, definations -homeostasis -components and types of feedback system -causes of cell injury -pathogenesis Cell membrane damage, mitochondrial damage, ribosome damage
- 3. INTRODUCTION Due to changes in external environment human body made changes within itself to make it equal with external environment. Internal environment = External Environment
- 4. HOMEOSTASIS It is a condition when our cells internal environment is constant with external environment Derived from 2 greek words HOMEOSTASIS= MOMEO + STASIS (same/constant) (state/phase) It means studying the constant/same by maintaining pH, temperature, acid-base balance. https://www.youtube.com/watch?v=S0WLVFK G2WI
- 5. FEEDBACK SYSTEM A system who responsing back Components of feedback system: All the body organ co-ordinate with each other to maintain homeostasis. This co-ordination of homeostasis is controlled by feedback system with the help of nuro-endocrine system It has three components – 1. Receptors 2. Control center 3. Effector
- 6. Receptors- It is a type of sensor or which receive/detects changes or other stimuli. Control center- It receive the signal from receptor through blood veins and analyze it Effector- It response to signal or stimuli receptor
- 8. NEGATIVE FEEDBACK • Negative feedback is the most common feedback loop in the biological system. • Negative feedback is the one to which the system reacts in such a way as to arrest the change or reverse the direction of change. • After receiving a message, the effectors send negative feedback signals back to the system. • Now the system stabilizes its own function and makes an attempt to maintain homeostasis. • Many homeostatic mechanism in the body function through negative feedback. • Negative feedback also regulates many systems in organisms
- 9. A thermostat is a device for regulating the temperature of a system so that the system's temperature is maintained near a desired setpoint temperature.
- 10. Glucose and Insulin Negative Feedback Loop Boy eating cake Increases Glucose Levels Stimulates β cells of pancreas to secrete insulin Insulin stimulates the cells to take up glucose from the blood. Lowers Blood Glucose levels CYCLE 1 (-)
- 11. CYCLE 2 Low Blood Glucose Levels Stimulated Alpha Cells in Pancreas Glucagon is released Glucagon stimulates liver cells to release glucose into the blood High blood glucose levels and Cycle 1 continues (-)
- 12. Temperature Regulation of the Body • Increased temperature causes vasodilatation (blood vessels near the surface of the skin dilate). • The large surface area allows heat to be lost from the blood and lowers the body temperature. Sweating also helps lower the temperature. Decreased temperature causes vasoconstriction (blood vessels constrict) and minimal heat loss occurs which helps maintain body temperature. Hair on the body provides insulation and helps maintain body temperature.
- 13. Positive Feedback • A positive feedback loop occurs when the output of a system acts to enhance the changes to the input of the system. • One example of a biological positive feedback loop is the onset of contractions in childbirth. – When a contraction occurs, the hormone oxytocin is released into the body, which stimulates further contractions. – This results in contractions increasing in amplitude and frequency.
- 14. • Another example is blood clotting. – The loop is initiated when injured tissue releases signal chemicals that activate platelets in the blood. – An activated platelet releases chemicals to activate more platelets, causing a rapid cascade and the formation of a blood clot. • Lactation involves positive feedback so that the more the baby suckles, the more milk is produced.
- 15. • In most cases, once the purpose of the feedback loop is completed, counter-signals are released that suppress or break the loop. – Childbirth contractions stop when the baby is out of the mother's body. – Chemicals break down the blood clot. – Lactation stops when the baby no longer nurses.
- 16. ROLE OF VARIOUS SYSTEMS IN THE BODY • Each body system contributes to the homeostasis of other systems. • No system of the body works in isolation. • Well being of the person depends upon the well being of all the interacting body systems. NERVOUS SYSTEM: The nervous system maintains homeostasis by controlling and regulating the other parts of the body. Regulating centers are located in the CNS, consisting of the brain and spinal cord.
- 17. ENDOCRINE SYSTEM • Endocrine system consist of glands which secrete hormones into the blood stream. • Each hormone has an effect on one or more target tissues, in this way the endocrine system • Regulates the metabolism and development of most body cells and body systems. • INTEGUMENTARY SYSTEM: • Synthesize vitamin D which interact with calcium and phosphorus absorption needed for bone growth, maintenance and repair. • Skin help to maintain balance by excretion of water and other solutes.
- 19. SKELETAL SYSTEM • Protection is the pivotal role occupied by the skeletal system. MUSCULAR SYSTEM: Also responsible for involuntary(breathing, digestion) and voluntary (walking, picking up objects) actions. CARDIOVASCULR SYSTEM: The cardiovascular system, in addition to needing to maintain itself within certain levels, plays a role in maintenance of the other body system
- 20. RESPIRATORY SYSTEM • Respiratory systems works in conjunction(Collaboration) with the cardiovascular system to provide oxygen to cells within every body system for cellular metabolism. • Also remove CO2 from lungs • Helps in maintain proper blood pH levels.
- 21. CELL INJURY • Cells are the basic unit of tissue, which forms organ and systems of body • Cell injury is defined as effect of variety of stress that causes changes in cell’s internal as well as external environment • The cellular response to stress depends on variety of factors and also the cell injury can be either reversible and irreversible. • It is a change or alteration in cells structure or functions due to some stress that exceed the ability of cells to handle it • When the intensity of stress is severe, cell may lead to death
- 23. Cellular Adaptation: It is a process of any cell to survive in any opposite or adverse situation. These are the temporary or permanent changes in the shape, size or type of cell. It occurred due to functional demand and revert back to its normal state and function. Eg. Atropy, hypertropy, hyperplasia.
- 24. REVERSIBLE CELL INJURY: If the stress applied on the cell is mild to moderate level when the applied stress is removed, cell recovered itself back to its normal state knoen as reversible cell injury IRREVERSIBLE CELL INJURY: It is the stress applied on the cell of very severe level then it may lead to cell death. Eg. Apoptosis, necrosis
- 25. Etiology/ Causes of cell injury There are variety of stress causes cell injury. The reasons for reversible and irreversible cell injury are same: They are mainly classified into 2 types: A. Genetic B. Acquired
- 26. GENETIC CAUSES: When cell injury occurs due to defect in genes or chromosomes, then these type of causes known as as genetic causes. These are of following types: 1. Develpomental defect 2. Cytogenic effect 3. Single gene defect 4. Multifunctional inheritance defect
- 27. DEVELOPMENTAL DEFECT: Occred in featal life CYTOGENIC DEFECT: Abnormalities of chromosomes. It can be either structural or functional SINGLE GENE DEFECT: Also known as MENDELIAN disorder. Occurred due to damage to single gene MULTIFUNCTIONAL INHERITANCE DEFECT: Multifactorial inheritance, also known as complex inheritance. Multifactorial inheritance is when more than 1 factor causes a health
- 28. Acquired causes Like genetic disorder there are many acquired disorders: •Hypoxia and Ischemia •Physical agents •Chemical agents and drugs •Microbial agents •Immunological agents •Nutritional derangements •Psychological factors
- 29. HYPOXIA AND ISCHEMIA: •Cells of body require oxygen and blood to generate energy and perform different functions. •Hypoxia is defined as loss of oxygen supply while •Ischemia is defined as loss of blood supply •Both are of the major causes for cell injury
- 30. • 2. Physical agents • Direct Physical Effects- Exposure of tissue to extreme heat or cold results in direct injury that is often irreversible, resulting in a pattern of coagulative necrosis. • Sudden changes in pressure can cause cellular disruption (e.g. a hammer blow to the thumb). • Electrical currents can cause direct breakdown of cellular membranes that may be irreversible.
- 31. 3. Chemical agents & drugs: • Common poisons (arsenic, cyanide, mercury) interfere with cellular metabolism. If ATP levels drop below critical levels, affected cells will die. • The list of pharmaceuticals that may have toxic effects on cells is enormous. • Some act directly, but most have their effect through breakdown metabolites. Metabolism of alcohol (a type of drug) to acetaldehyde is one example.
- 32. 4.Microbial agent • Injuries by microbes include infections caused by Fungi, Rickettsiae, Bacteria, parasites and Viruses 5. Immunologic agents: Double –edged sword’- protects the host against various injurious agents but it may also cause cell injury. • Hypersensitivity reactions • Anaphylactic reactions to a foreign body • Autoimmune diseases(allergies)
- 33. • 6. Nutritional Imbalances: • Both a lack of essential nutrients and an excess of certain nutrients can disrupt cellular functions and lead to damage. • Deficiencies in calories, protein, vitamins, or essential fatty acids can all impair cellular processes, while excessive intake of things like cholesterol or certain fats can also lead to cellular harm
- 34. 7. Psychogenic diseases: • No specific biochemical or morphologic changes in acquired mental diseases. • problems of drug addiction, alcoholism & smoking results in various organic diseases such as liver damage, chronic bronchitis, lung cancer, peptic ulcer, HT, IHD etc
- 35. Biochemical Changes: These involve changes in brain chemicals (neurotransmitters like dopamine, serotonin, norepinephrine). For example, two individuals with depression might show different neurochemical profiles. Morphologic Changes: This refers to changes in the structure or shape of brain tissue (as seen on imaging like MRI or CT scans) Acquired Mental Diseases: These are not present at birth but develop due to environmental, psychological, or physical factors. Examples: Depression, anxiety, schizophrenia (possibly both genetic and acquired)
- 36. 8. Genetic derangements: • Result in a defect as severe as the congenital malformations associated with down syndrome, caused by chromosomal abnormalities. • Inborn error of metabolism arising from enzymatic • abnormalities.
- 37. Pathogenesis/Mechanism of cell injury: It is process of causes of cell injury, which involve following steps: 1. Cell membrane damage 2. Mitochondrial damage 3. Ribosome damage 4. Nuclear damage
- 39. Pathogenesis of reversible cell injury: • Hypoxia or ischemia decreases generation of cellular ATP. • Sodium potassium pump damage leads to accumulation of sodium and water inside cell which ultimately causes cell swelling • Increased anaerobic glycolysis leads to increase formation of lactic acid which causes clumping of chromatin
- 40. Pathogenesis of irreversible cell injury: The pathogenesis of irreversible cell injury refers to the sequence of events by which a cell sustains damage that leads to permanent dysfunction and death, typically by necrosis or apoptosis. This usually follows prolonged or severe stress that the cell cannot adapt to or recover from. • Increased calcium influx: Mitochondrial damage • Phospholipase activation: Membrane damage • Protease activation: Protein damage • Endonuclease activation: Nuclear damage • Atpase activation: ATP Damage
- 41. 1. CELL MEMBRANE DAMAGE • Membrane of cell can be easily damaged by any type of destructive physical agents like heat or radiation • Loss of oxygen supply causes hypoxia, decreases ATP formation and due to this supply of essential material that cell needs to survive get reduced • Also influx of calcium ions in cell leads to cell injury
- 42. 2. MITOCHONDRIAL DAMAGE •Mitochondria are critical for cell survival, mainly due to their role in ATP production. When they are damaged beyond repair, it becomes a point of no return in irreversible cell injury. •Increased cytosolic calcium leads to increase in inorganic phosphate and certain fatty acids •Inorganic phosphate and fatty acids alone cannot damage the mitochondria but along with calcium ions they can damage
- 43. Causes of Mitochondrial Damage: • Hypoxia/ischemia reduces oxidative → phosphorylation. • Calcium overload in cytosol. • Reactive oxygen species (ROS) damage mitochondrial membranes. • Toxins (e.g., cyanide, alcohol, drugs). Consequences of Mitochondrial Damage: 1.Failure of Oxidative Phosphorylation Damaged inner mitochondrial membrane loss of → electron transport chain. 2.↓ ATP production energy failure cell death. → →
- 44. 3. RIBOSOMAL DAMAGE •Ribosomes are essential for protein synthesis in the cell. • Damage to ribosomes, or detachment from the endoplasmic reticulum (ER), severely impairs the cell’s ability to make proteins— this is a key feature of reversible injury, but when prolonged, it contributes to irreversible cell damage. •Decrease in ATP formation to detachment of ribosomes from rough endoplasmic
- 45. 3. NUCLEAR DAMAGE Nuclear damage is a hallmark of irreversible cell injury and a strong indicator that the cell is undergoing death — either by necrosis or apoptosis. Once nuclear structures are disrupted, the cell cannot recover. The decrease in ATP formation and loss of oxygen supply leads to increase anaerobic glycolysis which results into increased lactic acid formation This lactic acid leads to clumping of
- 46. MORPHOLOGY OF CELL INJURY -Adaptive changes are the adjustment made by cell in the response of stress -These changes can be physiological as well as pathological -Adaptive changes are generally related to change in size, shape, or type. -Following are the adaptions cell made in the reponses of stress • Atrophy • Hypertrophy • Hyperplasia • Metaplasia
- 47. MORPHOLOGY OF CELL INJURY Atrophy is a reduction in cell size and function. • It can be physiological (normal) or pathological (disease-related). • Caused by disuse, denervation, ischemia, malnutrition, hormonal loss, or pressure. • Involves decreased protein synthesis and increased degradation. • Atrophy found in heart, ske;etal muscle, brain.
- 48. MORPHOLOGY OF CELL INJURY Hypertrophy is an increase in the size of individual cells, leading to an increase in the size of the affected organ or tissue. The number of cells does not increase (that’s hyperplasia). It is occurred due to increased functional demand. It is either physiological or pathological
- 49. MORPHOLOGY OF CELL INJURY Hyperplasia is an increase in the number of cells in an organ or tissue, leading to an increase in size. Occurs mainly in tissues with cells capable of mitosis (e.g., epithelial and glandular tissues). Often occurs together with hypertrophy. Mechanism of Hyperplasia: Increased demand or hormonal stimulation → growth factors released. Enhanced DNA synthesis and mitosis.
- 50. MORPHOLOGY OF CELL INJURY Metaplasia is when one type of mature cell in your body changes into another type of mature cell. This usually happens because the new cell type is stronger and can handle things like irritation or injury better. For example, if the cells lining your windpipe get irritated by cigarette smoke, they might change from one kind of cell to another that is tougher and protects better. The good news is, this change can go back to normal if the irritation or stress stops.
- 51. MORPHOLOGY OF CELL INJURY Dysplasia is when cells in a tissue start to grow abnormally. The cells look different from normal cells — they might be irregular in size, shape, or organization. This is often a response to ongoing irritation or damage. Dysplasia isn’t cancer yet, but if the problem keeps going, these abnormal cells might turn into cancer later. Dysplasia is usually reversible if the irritating factor is removed early.
- 52. CELLULAR SWELLING •Accumulation of water in the cell •It occurs b’coz of imbalance in between sodium and potassium pump •Cellular swelling is the earliest and most common sign of reversible cell injury. •It happens when a cell takes in too much water, causing it to swell and look bigger under the microscope. Why does it happen? •When a cell is injured, its energy production (ATP) drops. •Without enough ATP, the sodium-potassium pump (Na⁺/K⁺-ATPase) fails. •Sodium (Na⁺) builds up inside the cell.
- 53. CELLULAR SWELLING •Swollen cells have distended organelles (like mitochondria and ER). •The plasma membrane becomes leaky and can develop blebs. •The cell can still recover if the injury is mild and removed.
- 54. INTRACELLULAR ACCUMULATION •Intracellular accumulation is simply defined as accumulation of abnormal substances that can temporarily or permanently damage a cell. •It can be occurs due to overproduction, abnormal metabolism •It can be either reversible or irreversible.
- 55. CALCIFICATION It is defined as accumulation of calcium in body tissues It is normally occurs in the formation of bone but abnormal deposition of calcium can disrupt body’s natural process Calcification can be occur almost in every part of and eventually leads to health problem It occurs due to hypercalcemia,
- 56. CALCIFICATION •Most of the body's organ functions at a cetrain pH range. •Disable in thes pH range can causes disturbance in functioning. Ideally pH of blood is 7.4 •If the pH of blood falls down 7.4 then it is defined as acidosis. •If the pH of blood goes above 7.4 then it is defined as alkalosis. •Acidosis and alkalosis are of two types: •Respiratory •Metabolic
- 57. ELECTROLYTE IMBALANCE • Bloodstream contains many chemical that are very essential for normal body functions. Electrolytes are one of them • Calcium, magnesium, sodium, potassium are some examples of electrolytes • Now imbalance in these electrolytes can cause variety of disturbance. • Electrolytes imbalance can become result into vomiting, diarria, sweating, high fever.
- 59. anaerobic glycolysis: a metabolic process where glucose is broken down in the absence of oxygen, resulting in the production of ATP and lactic acid Cell Swelling and Lysis: Accumulation of sodium within the cell, due to pump failure, can lead to osmosis, causing water to rush into the cell and potentially causing it to swell and rupture. Attached ribosomes synthesize proteins that are transported out of the cell via secretory vesicles The endoplasmic reticulum is involved in the transportation of substances throughout the cell. It plays a primary role in the metabolism of carbohydrates, synthesis of lipids, steroids and proteins. Ribosomes are the protein synthesisers of the cell.