Pathology Notes - Week 2 & 3 PDF

PATHOLOGY INTRODUCTION  PATHOLOGY Pathology is derived from the greek words Pathos meaning suffering and Logos meaning study DEFINITION Pathology - is a scientific study of structure and function of the body in disease; it deals with causes, effects, mechanisms and nature of disea...

PATHOLOGY INTRODUCTION  PATHOLOGY Pathology is derived from the greek words Pathos meaning suffering and Logos meaning study DEFINITION Pathology - is a scientific study of structure and function of the body in disease; it deals with causes, effects, mechanisms and nature of disease. Disease- opposite of health, is a loss of ease to the body  Health – is a condition when the individual is in complete accord with the surroundings Illness - is the reaction of the individual to the disease in the form of signs and symptoms.  Homeostasis - is the property of a system that regulates its internal environment and tends to maintain a stable, relatively constant condition of properties such as temperature or pH.  TERMINOLOGY Patient – person affected by disease Lesions – are the characteristic changes in tissues and cells produced by disease in an individual. Pathologic changes or morphology – consist of examination of diseased tissue. Form or structure of organisms.  Etiology – the causal factors responsible for the lesion, causes of disease. Pathogenesis – the mechanisms by which the lesions are produced, The development of a diseased or morbid condition. Signs and symptoms – the functional implications of the felt by the patient and discovered by the clinicians.  Diagnosis – The act or process of identifying or determining the nature and cause of a disease or injury through evaluation of patient history, examination, and review of laboratory data. Prognosis –a prediction of the course or outcome of a disease or disorder and the chances of recovery from a disease  Treatment –the application of medicines, surgery, psychotherapy, etc., to a patient or to a disease or symptom Prevention -The act of preventing or impeding. EVOLUTION OF PATHOLOGY From religious beliefs to rational approach(Antiquity to AD 1500) 1. Aesculapius – Greeks God of healing 2. Aristotle,Socrates,Plato – Introduced philosophical concepts to all natural phenomena. 3. Hippocrates (Greece) 460-377 BC – The great Greek clinical genius and regarded as the father of medicine. -started study of patients symptoms as method of diagnosis. -he introduced ethical concepts in the practice of medicine.(Hippocratic Oath). 4. Charaka and Sushruta (India) 200AD – Disequilibrium of Dhatus (elements constituting the body) as the cause of disease. 5. Cornelius Celsus (Rome) 53 BC-7 AD - Described 4 cardinal signs of inflammation (redness, heat, swelling, pain). 6. Claudius Galen (130-200AD) - Galenic(humoral)theory, suggested that the illness resulted from imbalance between four humors or body fluids. (blood, lymph, black bile, and biliary secretions from liver). -He wrote about 80 books on field of medicine Era of gross pathology (AD 1500 to 1800) 7. Vesalius (1514-1564) – started the dissection of human body. 8. Gabriel Fallopius (1523-1562) – who described human oviducts(fallopian tubes) 9. Fabricius – who discovered lymphoid tissue around the intestine of birds. 10. Anton Von Leeuwenhoek (1632- 1723) – invented the first ever microscope -introduced histological staining in 1714 using saffron to examine muscle fibres. 11. Marcello Malpighi (1632-1723) – father of histology, decribed the layer of skin and lymphoid tissue in the spleen. 12. Giovanni B. Morgagni (1682-1771) – excellent teacher in anatomy, foundation of clinicopathologic methodology in the study of disease. Introduced (CPC), 13. Sir Percival Pott (1714-1788) – famous surgeon in England, identified the first occupational cancer in the chimney sweeps in 1775 and as the first carcinogenic agent  14. John Hunter (1728-1793)- student of percival who become greatest surgeon- anatomist. -Who made a collection of more than 13,000 surgical specimens. -Father of museum in pathology 15. R.T.H. Laennec – French physician, he described several lung diseases and micronodular cirrhosis associated with heavy intake of alcohol. -Invented stethoscope 16. Carl F.von Rokitansky (1804-1878) – German pathologist who performed nearly 30,000 autopsies,he described acute yellow atrophy of the liver 17. Richard Bright (1793-1860) – who described non-suppurative nephritis later termed glomerulonephritis 18. Thomas Addison (1793-1860) – who gave an account of chronic adrenocortical insufficiency termed Addison’s disease 19. Thomas Hodgkin (1798-1866) – who observed the complex of chronic enlargement of lymph nodes, liver and spleen, later called Hodgkin’s disease. Era of Technology Development and Cellular Pathology (1800-1950) 20. Louis pasteur (1822-1895) – French chemist, discovery of existence of disease causing microorganisms 21. G.H.A. Hansen (1841-1912) –identified hansen’s bacillus as causative agent for leprosy (Hansen’s disease) in 1873. 22. Paul Ehrlich (1854-1915) – German physician, -conferred nobel prize for his work in immunology, used staining techniques of cells and bacteria -foundation of haematology 23. Christian Gram (1853-1938) – Danish physician, who developed bacteriologic staining by crystal violet. 24. D.L.Romanowsky (1861-1921) – Russian physician who developed stain for peripheral blood film using eosin and methylene blue derivatives. 25. Robert Kosh (1843-1910) – German bacteriologist, who developed techniques of fixation and staining for identification of bacteria -Discovered tubercle bacilli in 1882 and cholera vibrio organism in 1883. 26. May Grunwald and Giemsan – developed blood stains and applied them for classification of blood cells and bone marrow cells. 27. Sir William Leishman (1865-1928) – who described Leishman’s stain for blood films in 1914 and observed Leishman Donovan bodies 28. Robert Feulgen (1884-1955) – who described Feulgen reaction for DNA staining and laid the foundations of cytochemistry and histochemistry. 29. F.T. Schwann (1810-1882) – the first neurohistologist 30. Claude Bernarde (1813-1878) – pioneer in pathophysiology 31. Rudolf Virchow (1821-1905) – German pathologist, known as the father of cellular pathology 32. Karl Landsteiner (1863-1943) – described the existence of human blood groups in 1901 and was awarded nobel prize in 1930. 33. Ruska and Lorries (1933) – developed electron microscope which aided the pathologist to view ultrastructure of cell and its organelles. 34. George N. Papanicolaou (1883- 1962) – American pathologist, who developed Pap test for diagnosis of cancer of uterine cervix. - father of exfoliative cytology. Modern Pathology 1950’s to 21st century 35. Watson and Crick 1953 –introduced the structure of DNA of the cell 36. Tijo and Levan 1956 – Identify the chromosomes and their correct number in humans 37. Nowell and Hagerford 1960 – Identify chromosomes in chronic myeloid leukemia, the first chromosomal abnormality in any cancer. 38. Paul Berg 1972 – Recombinant DNA technique.  39. Kary Mullis 1983 - Introduced polymerase chain reaction (PCR) 40. Barbara McClintock 1983 – Discovered flexibility and dynamism of DNA  41. Ian Wilmut 1997 – Scottish scientist, used a technique of somatic cell nuclear transfer to create the clone of a sheep named Dolly. _ in 2004 Therapeutic cloning of human embryos for use in treating motor neuron disease; era of human stem cell research. SUBDIVISION 1. Histopathology - refers to the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopathology refers to the examination of a biopsy or surgical specimen by a pathologist 2. Haematology – deals with the diseases of blood. It includes laboratory haematology and clinical haematology. 3. Chemical pathology – Analysis of biochemical constituents of blood, urine, semen and etc.  It encompasses detecting changes in a wide range of substances in blood and body fluids (electrolytes, enzymes and proteins) in association with many diseases. It involves detecting and measuring tumour (cancer) markers, hormones, poisons and both therapeutic and illicit drugs. For example Chemical Pathologists are involved in assessing levels of iron in the blood. 4. Immunology –Detection of abnormalities in the immune system of the body. 5. Experimental Pathology - also known as investigative pathology is the scientific study of disease processes through the microscopic or molecular examination of organs, tissues, cells, or body fluids from diseased organisms. Defined as production of disease in the experimental animal and its study. 6. Geographic Pathology – The study of differences in distribution of frequency and type of diseases in populations in different parts of the world forms. 7. Medical Genetics – Deals with the relationship between hereditary and disease. It involves the diagnosis and management of hereditary disorders. 8. Molecular Pathology - is an emerging discipline within pathology which is focused in the study and diagnosis of disease through the examination of molecules within organs, tissues or bodily fluids. Molecular pathology shares some aspects of practice with both anatomic pathology and clinical pathology  TECHNIQUES FOR THE STUDY OF PATHOLOGY 1. AUTOPSY – the main purpose of autopsy are 1. Quality assurance of patient care -confirming the cause of death -establishing the final diagnosis -study of therapeutic response to treatment 2. Education of the entire team -Discovery of newer disease made at autopsy -Study of demography and epidemiology of diseases 2. Surgical pathology - Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons.The practice of surgical pathology allows for definitive diagnosis of disease. There are two major types of specimens submitted for surgical pathology analysis: biopsies and surgical resections  Biopsy - is a small piece of tissue removed primarily for the purposes of surgical pathology analysis, most often in order to render a definitive diagnosis. Surgical resection - specimens are obtained by the therapeutic surgical removal of an entire diseased area or organ. These procedures are often intended as definitive surgical treatment of a disease in which the diagnosis is already known or strongly suspected. 3. Basic Microscopy – Microscope is the basic tool of the pathologist. It is an instrument which produces greatly enlarged images of minute objects. The usual type of microscope used in clinical laboratories is called light microscope. (2 types) Simple microscope – this is a simple hand magnifying lens. The magnification power of hand lens is from 2x to 200x. Compound microscope – this has a battery of lenses which are fitted in a complex instrument. The objective lens and eye piece lens. MICROSCOPE -Microscope is the basic tool of the pathologist. It is an instrument which produces greatly enlarged images of minute objects. The usual type of microscope used in clinical laboratories is called light microscope.  2 types Simple microscope – this is a simple hand magnifying lens. The magnification power of hand lens is from 2x to 200x. Compound microscope – this has a battery of lenses which are fitted in a complex instrument. The objective lens and eye piece lens. Parts of the Microscope 1. Ocular Lens (Eyepiece) - where you look through to see the image of your specimen. Magnifies the specimen 10X actual size. 2. Body tube - the long tube that supports the eyepiece and connects it to the objectives. 3. Nosepiece - the rotating part of the microscope at the bottom of the body tube; it holds the objectives. 4. Arm - part of the microscope that you carry the microscope with; connects the head and base of the microscope. 5. Objective Lenses - (low, medium, high). Depending on the microscope, you may have 2, 3 or more objectives attached to the nosepiece; they vary in length (the shortest is the lowest power or magnification; the longest is the highest power or magnification).  6. Coarse Adjustment Knob - large, round knob on the side of the microscope used for "rough" focusing of the specimen; it may move either the stage or the upper part of the microscope. Location may vary depending on microscope - it may be on the bottom of the arm or on the top.  7. Fine Adjustment Knob - small, round knob on the side of the microscope used to fine-tune the focus of your specimen after using the coarse adjustment knob. As with the Coarse Adjustment Knob, location may vary depending on the microscope. 8. Stage - large, flat area under the objectives; it has a hole in it (see aperture) that allows light through; the specimen/slide is placed on the stage for viewing. 9. Stage Clips - clips on top of the stage which hold the slide in place. 10. Aperture - the hole in the stage that concentrates light through the specimen for better viewing. 11. Diaphragm - controls the amount of light going through the aperture; may be adjusted.  12. Light or Mirror - source of light usually found near the base of the microscope; used to direct light upward through the microscope. The light source makes the specimen easier to see. Cell structure and CELL INJURY THE NORMAL CELL ADAPTATION---(increase functional demand)--- atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia ---(stress removed)-- Normal Cell Restored REVERSIBLE CELL INJURY---(mild to moderate stress)--- degeneration, subcellular alterations, intracellular accumulations --- Repair and Healing IRREVERSIBLE CELL INJURY --- Cell Death STRUCTURE OF A CELL  components I. CELL MEMBRANE – or plasma membrane has a trilaminar structure having a total thickness of about 7.5nm --separates the interior of all cells from the outside environment. -- is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells.  The basic function of the cell membrane is to protect the cell from its surroundings. - gel like arrangement composed of complex mixture of phospholipids, glycolipids, cholesterol, proteins, and carbohydrates Glycocalyx – outer surface of cell. Proteins and glycoprotein - in cell membrane may act as antigens or may form a receptors - selective permeability that includes diffusion, mambrane pump and pinocytosis (cell drinking). II. NUCLEUS –consist of an outer nuclear membrane enclosing nuclear chromatin and nucleoli. The function of the nucleus is to maintain the integrity of the genes and to control the activities of the cell by regulating gene expression — the nucleus is, therefore, the control center of the cell. 1. Nuclear Membrane – is the outer envelop consisting of 2 layers of the unit membrane which are separated by a 40- 70nm wide space. --The space between the membranes is called the perinuclear space --the two layers of nuclear membrane are fused together forming a circular nuclear pores which are about 50nm in diameter. )  2. Nuclear Chromatin – The main substance of nucleus. -- is in the form of shorter pieces of thread like structures called chromosomes -- there are 23 pairs (46 chromosomes), 22pairs are autosomes and 1 pair for sex chromosomes. -- categorized into 7 groups from A to G, and composed of 3 components ( 20% deoxyribonucleic acid DNA, 10% ribonucleic acid RNA, and 70% consists of nuclear proteins  --DNA molecules consists of two complementary polypeptide chains forming a double helical strands which is wound spirally around an axis composed of pentose sugar-phosphoric acid chains. --composed of 4 nucleotide bases: 2 purines ( adenine and guanine), 2 pyrimidines ( cytosine and thymine)  3. Nucleolus – may contain one or more bodies called nucleoli. --the site of synthesis of ribosomal RNA --composed of granules and fibrils representing newly synthesised ribosomal RNA.  III. CYTOSOL and ORGANELLES CYTOSOL – or the CYTOPLASM is the gel like ground substance in which the organelles of the cells are suspended 1. CYTOSKELETON – responsible for maintaining cellular form and movement Microfilaments – are long filamentous structure having a diameter of 6-8nm. They are composed of contractile proteins, actin and myosin. Intermediate filaments – are filamentous structure, 10nm in diameter, and are cytoplasmic constituent of a number of cell types. They are composed of protein.  5 types of intermediate filaments cytokeratin - found in epithelial cell desmin - found in skeletal, smooth and cardiac muscles vimentin - found in cells of mesenchymal origin. (multipotent stromal cells that can differentiate into a variety of cell types, including:) --osteoblasts (bone cells), --chondrocytes (cartilage cells), --and adipocytes (fat cells).  glial fibrillary acidic protein - present in astrocytes and ependymal cells (astrocytes are characteristic star- shaped glial cells in the brain and spinal cord. They are the most abundant cell of the human brain.) (ependymal cells. are a type of Glial cell and are also CSF producing cells. Within the brain's ventricles)  neurofilaments – seen in neurons (Their main function is to mechanically integrate the cell organelles within the cytoplasm) Microtubules – are long hollow tubular structure about 25nm in diameter. Cilia and flagella are composed of microtubules and are active in locomotion of the cell.  2. MITOCHONDRIA – are oval structures and are more numerous in metabolically active cells. They are enveloped by two layers the outer layer and inner layer. --small spherical to rod-shaped cytoplasmic organelles, enclosed by two membranes separated by an intermembranous space; the inner membrane is infolded, forming a series of projections (cristae). Mitochondria are the principal sites of ATP synthesis --the matrix of mitochondria contains enzyme required in krebs cycle by which the products of carbohydrates, fat and protein metabolism are oxidised to produce energy in the form of ATP --powerhouse of the cell  3. RIBOSOMES – an organelle composed of RNA and protein that functions in the synthesis of protein. Ribosomes interact with messenger RNA and transfer RNA to link amino acid into a polypeptide chain. Ribosomes may exist singly, in clusters as polysomes, or attached to the "rough" endoplasmic reticulum. --are spherical particles which contain 80-85% of the cells RNA.  4. ENDOPLASMIC RETICULUM – is composed of vesicles and intercommunicating canals whose main function is the manufacture of protein.  2 forms of ER -- rough endoplasmic reticulum (granular) – because its outer surface is rough or granular due to attached ribosomes -- smooth endoplasmic reticulum (agranular)-- are involved in the synthesis of lipids, including oils, phospholipids and steroids, metabolizing of carbohydrates, regulation of calcium concentration and detoxification of drugs and poisons.  5. GOLGI APPARATUS OR COMPLEX – is generally located close to the nucleus. It primarily modifies proteins delivered from the rough endoplasmic reticulum but is also involved in the transport of lipids around the cell, and the creation of lysosomes. --The Golgi apparatus is integral in modifying, sorting, and packaging these macromolecules for cell secretion (exocytosis). It is also a major site of carbohydrate synthesis. 6. LYSOSOMES – are rounded to oval membrane bound organelles containing powerful lysosomal digestive enzymes. --contain acid hydrolase enzymes that break down waste materials and cellular debris. --They can be described as the stomach of the cell. varies from 0.1–1.2 μm  3 forms of lysosomes -primary ( storage vacuoles) – are formed from the various hydrolytic enzymes synthesised by the RER and packed in golgi apparatus. -secondary ( autophagic vacuoles) – are formed by fusion of primary lysosomes with the parts of damaged or worn out cell components.  -(residual bodies) – are indigestable materials in the lysosomes e.g. lypofuscin (is the name given to finely granular yellow- brown pigment granules composed of lipid- containing residues of lysosomal digestion. It is considered one of the aging or "wear- and-tear" pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells.)  7. CENTRIOLE OR CENTROSOME – these are seen as two small structures composed of electron-dense fibrils. They perform the function of formation of cilia and flagella and form the spindle of fibrillary protein during mitosis.  IV. INTERCELLULAR JUNCTIONS - plasma membrane of epithelial cell and endothelial cell are separated from each other by 20nm wide spread. These cells communicate across this space through intercellular junctions  4 types of intercellular junctions 1. Occluding junction ( Zonula occludens) – these are tight junctions situated just below the luminal margin. As a result, the regions of occluding zones are impermeable to macromolecules.* 2. Adhering junctions (Zonula adherens) – these are located just below the occluding zones. These zones are in contact with actin microfilament  3. Desmosome (Macula densa) – these are tiny adhesions plates present focally between the adjacent epithelial cells, especially in epidermis. Occuring at the basal region 4. Gap junction (nexus) - are the regions on the lateral surfaces of epithelial cells where the gap between the adjoining plasma membrane is reduces from 20nm to 2nm. Pits or hole  (play vital roles in the human body, including their role in the uniform contractile of the heart muscle.They are also relevant in signal transfers in the brain, and their absence shows a decreased cell density in the brain. Retinal and skin cells are also dependent on gap junctions.) Gap adherens tight desmosome  MOLECULAR INTERACTIONS BETWEEN CELLS All cells in the body including circulations constanly exchange information with each other. This process is accomplished in the cells by chemical agents. 1. Cell Adhesion Molecules (CAMs) 2. Cytokines 3. Membrane Receptors 1. Cell Adhesion Molecules (CAMs) The molecules responsible for creating cell junctions include various cell adhesion molecules. There are 4 main types: selectins, cadherins, integrins, and the immunoglobulin superfamily.  Selectins - are cell adhesion molecules that play and important role in the initiation of inflammatory processes. -L-selectin, P-selectin and E-selectin. L-selectin deals with lymphocytes, monocytes and neutrophils, P-selectin deals with platelets and endothelium and E-selectin deals only with endothelium. Cadherins are extremely important in the process of morphogenesis – fetal development. --calcium dependent adhesion molecules which bind adjacent cell together and prevent invasion of cancer cells  Integrins act as adhesion receptors, transporting signals across the plasma membrane in multiple directions. Immunoglobulin superfamily are a group of calcium independent proteins capable of homophilic and heterophilic adhesion. (Cell adhesion is a vital component of the body. Loss of this adhesion effects cell structure, cellular functioning and communication with other cells and the extracellular matrix and can lead to severe health issues and diseases.) 2. CYTOKINES --These are soluble proteins secreted by haemopoietic and non-haemopoietic cells in response to various stimuli. --their main role is in activation of immune system --presently, about 50 cytokines have been identified and are grouped in 6 categories  1. Interferons (IFN) 2. Interleukins (IL) 3. Tumour necrosis factor (TNF, cachectin) 4.Transforming group factor (TGF) 5. Colony stimulating factors (CSF) 6. Growth factor  3. Cell membrane receptors Cell receptors are molecules consisting proteins, glycoproteins or lipoproteins. 3 main types of receptors 1. Enzyme-linked receptors – are involved in control of cell growth (e.g. tyrosine kinase- activity in the nucleus involves cell-cycle control. is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions.)  2. Ion channel – the activated receptor for ion exchange such as for sodium, potassium and calcium and peptide hormones determines inward or outward movement of these molecules. --pore-forming proteins that help establish and control the voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient.  3. G-protein receptors – these are trans-membranous receptors. --constitute a large protein family of receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. They are called transmembrane receptors because they pass through the cell membrane, and they are called seven-transmembrane receptors because they pass through the cell membrane seven times. --also known as second messenger activation. Cell cycle Mitosis - is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly equal shares of these cellular components Meiosis – multiplication of germ cells  PHASES of cell cycle 1. Interphase - cell prepares itself for cell division. Interphase is divided into three phases: G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. interphase  2. Prophase - At the onset of prophase, chromatin fibers become tightly coiled, condensing into discrete chromosomes. It is crucial for the reader to note that chromatin is a complex consisting of both chromosomes and specific proteins. Since the genetic material has already been duplicated in S phase, the replicated chromosomes have two sister chromatids, prophase  3. Metaphase – The microtubules become arranged between the two centrioles forming spindle, while the chromosomes line up at the equatorial plate of the spindle. --the two centrosomes start pulling the chromosomes through their attached centromeres towards the two ends of the cell. metaphase  4. Anaphase – The centromeres divide and each set of separated chromosomes moves towards the opposite poles of the spindle. Cell membrane also begins to divide anaphase  5. Telophase – There is formation of nuclear membrane around each set of chromosomes and reconstitution of the nucleus. The cytoplasm of the daughter cells completely separates. telophase CELL INJURY  Etiology of cell injury 2 large group causes of cell injury 1.Acquired causes 2.Genetic causes Acquired causes of cell injury can be categorised as under --hypoxia and ischaemia (reduced supply of blood to cell) --physical agents (mechanical trauma—road accident, thermal trauma, electricity, radiation) --chemical agents and drugs (insecticides, pollutants, chemical poisons like cyanide)  --microbial agents (infection caused by bacteria, viruses, parasites) --immunologic agents (hypersensitivity reactions, autoimmune diseases) --nutritional derangements (deficiency of nutrients like starvation, anaemia) --psychological factors (problems of drug addiction, alcoholism and smoking)  Pathogenesis of cell injury (development) General Reduced ATP synthesis/mitochondrial damage Loss of calcium homeostasis Disrupted membrane permeability Free radicals Reversible (if its short duration, the effects are reversible) Loss of ATP – (atp derived from 2 sources, by aerobic respiration and by anaerobic glycolytic pathway) Reduced intracellular pH – due to low oxygen supply to the cell, aerobic respiration by mitochondria fails first.  Ultrastructural changes – (e.g detachment of ribosomes in RER, mitochondrial swelling, reduced synthesis in ribosomal RNA) Functional consequences – (e.g myocardial contractility ceases in 60seconds of coronary occlusion but can be reversed if circulation is restored) Reduced protein synthesis – as a result of continued hypoxia, ribosomes detached from RER Irreversible (cell death) – continuation of reversibly injured cell. 2 essential phenomena are: Mitochondrial dysfunction – as a result of continued hypoxia. Membrane damage – disturbance in cell membrane is the most important event in irreversible cell injury. Morphology of cell injury (structure) reversible 1. cellular swelling ( bacterial toxins, chemicals, poison, burns, high fever) 2. fatty change (intracellular accumulation of neutral fat, common in liver..) 3. hyaline change (glassy, homogeneous, eosinophilic appearance) 4. mucoid change (mucous secreted by mucous gland) Irreversible (cell death) Autolysis – (self-digestion) can occur in the living body when it is surrounded by inflammatory reaction. There is complete absence of surrounding inflammatory response. Necrosis – defined as focal death. is caused by factors external to the cell or tissue, such as infection, toxins, or trauma that result unregulated digestion of cell components.  5 types of necrosis - coagulative necrosis – mostly from sudden cessation of blood flow (ischaemia) and less often in bacterial and chemical agents. Commom affected are the heart, kidney and spleen. - liquefaction (colliquative) necrosis – occurs commonly due to ischaemic injury and bacterial or fungal infections. Ex. Infarct brain and abscess cavity.  - caseous necrosis - is found in the center of foci of tuberculous infections. It combines features of both coagulative and liquefactive necrosis. - fat necrosis – special form of cell death occuring at two different locations (acute pancreatic necrosis and traumatic fat necrosis commonly in breast) - fibrinoid necrosis - characterised by deposition of fibrin-like material which has the staining properties of fibrin. It is encountered in various examples of immunologic tissue injury (e.g. autoimmune diseases), or in peptic ulcers.  Apoptosis – involvement of clusters of single cells or small clusters of cells. The apoptotic cells are round to oval shrunken. Shrinkage of cell with dense cytoplasm and almost normal organelles. There is no acute inflammatory reaction  Gangrene – a form of necrosis. Inflammation provoked by bacteria resulting in massive tissue necrosis. - the type of necrosis is usually coagulative due to ischaemia. - is characterized by primarily inflammation provoked by virulent bacteria resulting in massive tissue necrosis.  3 forms of gangrene Dry gangrene - this form of gangrene begins in the distal part of a limb due to ischaemia.* Wet gangrene – this occurs in naturally moist tissues and organs such as the mouth, bowel, lung, cervix. Diabetic foot and bed sores is another example. Gas gangrene – is a special form of wet gangrene caused by gas-forming clostridia (anaerobic bacteria) which gain entry into the tissues through open contaminated wounds.  Pathologic calcification – or heterotopic calcification is the deposition of calcium salts in tissues.  2 distinct type - dystrophic calcification – deposition of calcium salt in dead tissues (caseous necrosis in tuberculosis, fat necrosis, thrombi, dead parasites, breast cancer) and degenerated tissues ( cysts, stroma of tumour, atheromas, calcinosis cutis) - metastatic calcification – occurs in normal tissues due to hypercalcaemia, its causes would include: excessive mobilisation of calcium from the bone (hyperparathyroidism, bony destructive lesions) and excessive absorption of calcium from the gut (hypervitaminosis, milk alkali syndrome)  (Matastatic calcification may occur in any normal tissue of the body but affects the organ such as kidneys, lungs, stomach, blood vessels, cornea.) Reference Textbook of Pathology 5th edition by: Harsh Mohan Thank You….