1. 1. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 1
2. 2. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 2 Dedication To my students of the third stage in Dentistry faculty at Aliraqia university with best wishes. Prof.Dr. Khalil HassanAljeboori The admonstrator
3. 3. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 3 Topics of Lectures First Term Lectures 1-Introduction 2-Degenerative changes and cellular injury 3- Necrosis and apoptosis (Irreversible cell injury). 4- Disturbances of Pigmentation. 5- Inflammation. 6- Tissue repair healing and regeneration. 7- Cellular adaptation and disturbances of growth. 8- The Infectious Disease I 9- The Infectious Disease II 10- Disturbances of body fluids and electrolytes I 11- Disturbances of body fluids and electrolytes II 12- Immunopathology. 13-Neoplasia (tumors). 14-Ionizing radiation. 15-Genetic diseases Second Term Lectures 16- Cardiovascular system I 17- Cardiovascular system II 18- Cardiovascular system III 19- Diseases of respiratory system I 20- Diseases of respiratory system II 21- Diseases of respiratory system III 22- Diseases of Alimentary system I 23- Diseases of Alimentary system II 24- Diseases of Alimentary system III 25- Diseases of liver and pancreas I 26- Diseases of liver and pancreas II 27- Pathology of Lymphoid System I 28- Pathology of Lymphoid System II 29-Hematopathology I 30-Hematopathology II
4. 4. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 4 Contents Lecture 1: Introduction 13 -Normal cell composition -Definitions -Fields of pathology Lecture 2: Degenerative changes and cellular injury 15 1.Gloudy swelling 2-Hydropic degeneration 3- Fatty change or steotosis 4- Hyaline degeneration A. Connective tissue hyaline B. Epithelial hyaline 5- Glycogen infiltration A. metabolic disease diabetes mellitus B. glycogen storage disease Lecture 3: Necrosis and apoptosis(Irreversible cell injury) 19 *Apoptosis *Necrosis: 1.coagulative necrosis 2. Liquefactive necrosis 3. Caseous necrosis 4. Fat necrosis 5. Gangrenous necrosis 6. Fibrinoid necrosis * Fate of necrosis Lecture 4: Disturbances of Pigmentation 22 *Exogenous pigments *Endogenous pigment *Disturbances of minerals 1. Dystrophic calcification 2. Metastatic calcification *Gout Lecture 5: Inflammation 24 Purpose of inflammation and the inflammatory exudates. Clinical signs or hallmarks of inflammation Exudates or exudation Transludate (non inflammatory edema)
5. 5. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 5 Major important mediator of inflammation Types of inflammation 1- According to duration 2- According to exudates A) Acute inflammation 1-Serous inflammation 2-fibrinous inflammation 3-Hemorrhagic inflammation 4-Purulent (supportive) inflammation 5- Necrotizing or pseudo membranous inflammation 6-Allergic inflammation B) Chronic inflammation Granuloma Systemic effects of inflammation Consequence of excessive inflammation action Lecture 6: Tissue repair healing and regeneration 29 Regeneration Repair A)Healing by first intention Stages of wound healing by first intention B) Healing by second intention Factors affecting wound healing 1-Local 2-systemic Lecture 7: Cellular adaptation and disturbances of growth 31 Adaptation 1. Hypertrophy 2. Atrophy 3. Hyperplasia 4. Metaplasia Dysplasia Anaplasia Lecture 8: The Infectious Disease I 33 Infection Defenses mechanism 1-Nonspecific defense mechanism 2- Specific defense mechanism Mechanism of virus damage to cells Mechanism of bacterial injury, and damage to tissue Lecture 9: The Infectious Disease II 36 -Some human infectious diseases.
6. 6. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 6 Viral diseases Bacterial infections Parasitic infection Mycotic infection Lecture 10: Disturbances of body fluids and electrolytes I 43 Extra cellular fluid Intracellular fluid Fluid and electrolyte balance 1. Sodium 2. Potassium 3. Chloride Causes of edema (transudate) Pathological features of edema: 1-Subcutaneous edema 2-Pulmonary edema 3-Brain edema Clinical significance of edema Hyperemia and congestion Hemorrhage Types of hemorrhage Lecture 11: Disturbances of body fluids and electrolytes II 49 Ischemia Thrombosis Fate of thrombosis Embolism Infarction 1- Red infarction 2- White infarction 3- Septic infarction Shock Categories of shock Pathological changes in shock Lecture 12: Immunopathology 55 1) In adequate immune response a. Primary immunodeficiency b. Secondary immunodeficiency Acquired immunodeficiency syndrome (AIDS) 2) In appropriate immune response. Autoimmune diseases Immunological tolerance Classification of autoimmune diseases 3) Hypersensitivity or immunological injuries 1- Type I hypersensitivity reaction or anaphylaxis 2- Type II hypersensitivity, cellular cytotoxicity or cellular lysis 3- Type III hypersensitivity
7. 7. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 7 4- Type IV hypersensitivity Cell mediated cytotoxicity 4)Amyloidosis Lecture 13: Neoplasia (tumors) 71 Nomenclature of neoplasms Biology of tumor growth 1. Malignant transformation 2. Growth rates of tumor cells 3. Local invasion 4. Metastasis Precancerous condition Cellular effector mechanism against the tumor Effect of tumor on the host Grading and staging Tumor markers Carcinogenesis Lecture 14: Ionizing radiation 81 Ionizing radiation 1. Electromagnetic radiation 2. Particulate radiation Irradiation effects Tissue changes Result of irradiation Lecture 15: Genetic diseases 83 Types of genetic diseases - Chromosomal abnormalities A. Abnormalities of Chromosome number B. Abnormalities of Chromosome structure C. Chromosomal mosaicism - Inherited disorders (gene abnormalities) A. Pattern of inheritance B. Inherited metabolic disorders 1-disorder of carbohydrate metabolism 2-disorder of carbohydrate metabolism 3-disease of amino acid metabolism 4- Disorders of lipid metabolism 5 -lipid storage disease Lecture 16: Cardiovascular system I 90 -Diseases of Arteries Arteriosclerosis Medial sclerosis Endoarteritis oblitrans Arteriosclerosis
8. 8. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 8 Arteritis Thromboangitis oblitrans Aneurysm - Diseases of vein Varicose veins (varicosities) Phlebitis Venous thrombosis Neoplasms Lecture 17: Cardiovascular system II 94 - Diseases of lymph Lymphangitis Tumors of blood and lymphatic vessels - Diseases of heart Coronary heart disease. Hypertensive cardiopathy. Rheumatic heart disease. Congenital heart disease. - Diseases of endocardium Endocarditis Valvular deformities Carcinoid cardio-vascular disease Lecture 18: Cardiovascular system III 98 - Diseases of myocardium Coronary sclerosis. Coronary occlusion. Coronary thrombosis. Myocardial infraction Hypertrophy of heart. Hypertensive heart disease. Myocarditis. Metabolic disease. Heart block. - Diseases of pericardium Pericarditis. Tuberculous pericarditis Constrictive pericarditis (picks disease) Polyserositis (Concatos disease) Hydropericardium Hemopericardium Lecture 19: Respiratory system I 103 -The nose and nasal sinuses -Diseases of larynx -Diseases of bronchi 1. Chronic bronchitis
9. 9. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 9 2. Bronchial asthma 3. Bronchiectasis - Diseases of lungs 1. Chronic venous congestion 2. Edema 3. Thrombosis and embolism 4. Infarction Lecture 20: Respiratory system II 107 -Pneumonia 1. Labor pneumonia 2. Lobular pneumonia (bronchopneumonia) 3. Interstitial pneumonia -Rheumatic pneumonia -Lung abscess -Pulmonary tuberculosis (granulomatous pneumonia) -Pulmonary bilharziasis -Pulmonary hypertension -Obstruction -Atelactasis Lecture 21: Respiratory system III 111 -Emphysema 1. Obstructive emphysema 2. Senile emphysema occur in small lung 3. Pulmonary interstitial emphysema -Pneumoconiosis 1.Anthracosis 2.Silicosis 3. Asbestosis 4. Silicosiderosis 5. Berylliosis 6.Byssinosis 7.Bagassosis 8. Farmer lungs 9. Alveolar pronteinosis - Tumors of the lungs 1. Benign tumors 2. Malignant tumors - Diseases of pleura 1. Pleurisy, pleuritis 2. Empyema 3. Pleural effusion a. Hydrothorax b. Hemothrax c. Pneumothorax - Hemoptysis - Coin lesions
10. 10. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 11 Lecture 22: Diseases of Alimentary system I 116 - Lesion of oral cavity - Ulcers of stomach - Tumors Lecture 23: Diseases of Alimentary system II 121 - Intestinal tract diseases 1.Congenital malformations 2.Diverticula of intestine 3.Inflammation and ulcerations 4.Tumors of intestine 5.Intestinal obstruction Lecture 24: Diseases of Alimentary system III 127 - Diseases of periton 1. Ascites 2. Intraperitoneal hemorrhage 3. Peritonitis - Tumors - Hemorrhoids (piles) - Anal vistula - Pilonidal sinus - Celiac diseases and sprue 1. Celiac diseases 2. Tropical sprue 3.Protein losing-enteropathy (exudative enteropathy) 4. Whipples disease (intestinal lipodystroply) Lecture 25: Diseases of liver and pancreas I 132 - Circulatory disturbances - Infections of liver 1. Pyogenic abscesses 2. Pylephlebitis 3. Tuberculosis 4. Visceral leishmaniasis (kala-azar) 5. Amebic abscess 6. Weils disease 7. Syphilis 8.Viral hepatitis 9.Yellow fever 10.Hydatid cyts 11.Schistosomiasis (bilharziasis) 12.Actionomycosis abscesses -Cirrhosis of liver Distinctive patterns of cirrhosis
11. 11. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 11 Cirrhosis in infancy and childhood Liver Neoplasms Lecture 26: Diseases of liver and pancreas II 138 - Diseases of Gallbladder and bile ducts Cholecystctis Cholesterolosis Cholelithiasis Jaundice - Disease of pancreas Acute hemorrhagic pancreatitis Acute interstitial pancreatitis Chronic pancreatitis Cysts Fibrocystic disease Lesions Calculi Diabetes mellitus - Lesions in kidneys - Lesions in cardiovascular system Hematochromatosis Tumors Lecture 27: Pathology of Lymphoid System I 144 -Diseases of spleen Infectious splenomegaly Non-infectious splenomegaly - Diseases of the thymus Thymic hyperplasia Tumors Lecture 28: Pathology of Lymphoid System II 147 - Diseases of lymph nodes Reactive hyperplasia Acute nonspecific lymphadenitis Chronic nonspecific lymphadenitis Granulomatous lymphadenitis Lymphoid tumors Lecture 29: Hematopathology I 151 -Diseases of erythropoietic system Anemia 1. Deficiency anemia 2. Hypopoietic anemia
12. 12. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 12 Acute hemolytic anemia Acquired and congenital icterus Sickle cell anemia Mediterranean anemia: (thalassemia) Erythroblastosis fetalis. Polycythemia. Polycythemia vera Purpura Lecture 30: Hematopathology II 169 - Diseases of leukopoietic system Neutrophilic leukocytosis Eosinophilic leukocytosis (eosinophilia) Basophils leukocytosis Monocytosis Lymphocytosis Agranulocytosis Leukemia
13. 13. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 13 Lecture 1 Prof.Dr. Khalil Hassan Zenad Aljeboori Introduction Compositions: The normal cell: composed mainly 1. Nucleus 2. Cytoplasm 3. Cell membrane. The nucleus: contain chromosomes a carriers for genes and nucleolus. It is the heart of cell maintaining the genetic constitution of cell, namely chromosome network responsible for hereditary characters cell production and proliferation. The cytoplasm: contain organelles mitochondria, endoplasmic reticulum, Golgi apparatus. The dominant constituents of nucleus and cytoplasm the ribose nucleic acid (RNA) in the mitochondria and in nucleolus and deoxyribose nucleic acid in nucleus particular in chromosomes. The cell membrane: regulate internal environment of cells determine what is goes in and what is come out it is surface structure consisted of lipid, polysaccharides and small amount of protein. Mitochondria: main power plant of cell have different enzymes utilize molecular oxygen and distribute energy yielding component to other organelles and responsible for cell respiration. Endoplasmic reticulum: series of vesicles, canals responsible for protein synthesis. Golgi apparatus: remove cell products to outside. Pathology: is the science which deal with disease causes, nature of disease together with anatomical and functional changes induced by disease. Disease: is any departure of a state of health. Etiology of disease: bacteria and parasite, fungi, viruses, chemical, toxins, heat, cold, light, electricity, irradiation, foreign body, trauma, immunological, disorders.
14. 14. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 14 Nature of disease: 1. Congenital 2. Inflammation 3. Degeneration 4. Physical disturbances circulatory, trauma, obstruction of hollow organs foreign body, hernia, thermal disturbances, light electricity, irradiation, chemical) 5. Tumors Pathogenesis: the development of disease. Prognosis: result of an attack of disease. Complication of disease, new disorders occurred after usual course of disease. Symptoms: functional evidence of the disease. Example pain. Signs: objective evidence of the disease. Syndrome: a set of symptoms occur together. Field of pathology: 1. Histopathology: concerned with investigation and diagnosis of disease by tissue examination. 2. Gross pathology: refers to changes in organs or tissue in disease by naked eye (morbid anatomy) or (post mortem pathology) 3. Clinical pathology: is concerned with analysis of disease itself using laboratory methods or techniques. 4. Cytopathology: concerned with examination of cells to reach diagnosis of disease. 5. Hematology study: the blood and blood forming tissue. 6. Comparative pathology: is the study disease of lower animal comparable to human disease. 7. Physiological pathology: study changes in physiology in disease. 8. Experimental pathology: study the disease experimentally in animal model. 9. Immunopathology: study the disturbances affecting defenses mechanism of body related of disease process. 10. Chemical pathology: study the disease and diagnosis from chemical changes. 11. Toxicology: study the effects of poisons in the body. 12. Genetics: study abnormal chromosomal alteration and genes related to disease process. 13. Forensic pathology: application of pathology to legal purposes i.e. investigation of death in suspected circumstances. End Of Lecture 1
15. 15. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 15 Lecture 2 Prof.Dr. Khalil Hassan Zenad Aljeboori Degenerative changes and cellular injury 1- Cloudy swelling : reaction of cells to injury by swelling and accumulation of the water in their organelles or albumin so called albuminous or parenchymatous degeneration it usually reversible type of cell injury , most of acute infection or toxic condition are accompanied by cloudy swelling , mostly seen in liver , kidney . Grossly: Affected area in organ was swollen, capsule is tense and bulging during cut section, organ opaque. Microscopically: The affected cell are swollen, granular cytoplasm due to aggregate protein or albumin and water in cells organelles such as mitochondria, endoplasmic reticulum so the cell cytoplasm as ground glass appearance. Causes: 1- Hypoxia. A. O2 in blood,decrease. B. Ischemia I.e. No oxygenated blood reach tissue due to thrombus. C. Reduce oxygen capacity of RBCS due to anemia and CCl4 toxicity. 2- Chemical agents, ethanol,CO2. 3- Infections. 4- Genetic defects. 5- Nutritional imbalances. 6- Immunological reactions Ag- Ab complexes. 7- Aging. 8- Physical agents, radiation and electric shock. * All these agents cause disturbances in oxidation- phosphorylation process (energy, ATP) in cell membrane and plasma membrane so Na+ and water or albumin pumped inside cell cytoplasm or cell organelles resulted to cell swelling. The pumping of these materials are through pores in the cell membrane or plasma membrane. 2-Hydropic degeneration : Hydrops or vacuolar degeneration While in cloudy swelling there is too little amount of water in cell organelles, in hydropic degeneration too much amount of water in the cell cytoplasm is related to severity of the etiological agents, So the organ;
16. 16. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 16 Grossly: Swollen but more degree than in cloudy swelling. Microscopically: Clear spaces (water or albumin) these removed during tissue processing so appear clear spaces irregular or hazy borders in liver, kidney. Cause: Similar to cloudy swelling but extensive degree. Blisters: Specific defect of hydropic degeneration in which cystic swelling filled with water or albumin surrounded by thin membrane. Causes: A. hot metallic materials. B. Hot oil &water. C. Hard materials. D. Virus herpes virus. 3- Fatty change or steotosis Abnormal accumulation of fat droplets in cell cytoplasm of the parenchymal cells, kidney, heart and liver. Grossly: Seen mostly in liver, kidney and heart target organs for fat metabolism (triglycerides mainly) so the affected organs are yellow, fatty in nature, greasy inconsistency. Microscopically: Fat droplets appear as clear spaces with regular borders in the cytoplasm, these vacuoles or clear spaces coalesce together to form large vacuole displace the nucleus to the periphery. The clear space originally was fat droplets removed during the tissue processing under the effect of alcohol or xylole in (H&E) by special stain: Fat droplets: staining Sudan iii orange Sudan IV pink Osmic acid black Causes: 1- Toxins,alcohol, ethanol. 2- Metabolic disease diabetes mellitus. 3- Obesity (normally extra cellular fat). 4- Protein malnutrition lipoproteins. 5- Anoxia. 6- Starvation release fatty acids from adipose tissue.
17. 17. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 17 Disturbances in metabolism of cholesterol: abnormal level of cholesterol termed hyper cholesterolemia occur in; A. hypothyroidism. B. some renal disease. C. lipoid nephrosis. D. biliary obstruction. *so deposition of cholesterol in tissue occur such as in atherosclerosis, in gall bladder, old hemorrhage, necrotic tissue, the macrophages in contact with these lipid debris and engulf the lipid appear as a foamy appearance of their cytoplasm so called foam cells . In atherosclerosis both the smooth muscle and macrophages are filled with these lipid. *Similarly in the hereditary hyperlipidemia and in acquired hyperlipidemia the macrophage filled with these lipid form masses in the dermis and tendon called: A. Xanthomas. B. Gauchers disease in which lipid in spleen, brain, skin. C. Neimann pick disease in all tissues. 4- Hyaline degeneration: after line degeneration translucent, homogenous, structure less, materials, protein in nature and stain eosinophilic. Types: A. Connective tissue hyaline: occur in pleura, spleen capsule, corpus albicans C.T hyaline in arteriosclerosis in both the fibroblast lose their nuclei and old age tissue injury. B. Epithelial hyaline which occur: In the kidney when more albumin excrete and accumulated in PCT epithelial hyaline droplet, occur in case of nephrotic syndrome in which combine albumin with lysosomes in PCT epithelium by pinocytosis . in kidney hyaline casts when albumin or protein aggregated renal tubules. Or in liver in case of alcoholic hepatitis Mallory bodies. Immunoglobulin proteins aggregated in plasma cells Russel bodies. In prostate corpora amylacea also aggregation of protein hyaline, Onion like appearances in prostatic acini protein. in brain Alzheimer disease a Neurofibrillary tangle (NFTs) protein in neuron cells aggregated.
18. 18. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 18 C. Keratohyaline: in skin which indicate extensive thickening of stratum corneum, keratin without nuclei for examples hand calluses and foot corns. Causes: 1. Prolonged irritation and friction. 2. Warts viral disease papilloma virus and pox virus. 3. Ichthyosis fish scaly skin congenital disease. Specific type Zinker degeneration is a hyaline degeneration occur in skeletal muscles fibers described by zinker occur due to extensive bacterial toxins or excessive accumulation of lactic acid, so muscles pale friable and loss of striation due to lack of vitamin E . 5- Glycogen infiltration: normally in liver, SK. muscles excessive intracellular deposits of glycogen are associated with the abnormalities in the metabolism of either glucose or glycogen. Causes: A. metabolic disease diabetes mellitus in which abnormal glucose metabolism, so glycogen accumulates in kidney and cardiac muscles. B. glycogen storage disease in which defect in enzyme synthesis or breakdown of glycogen resulted into massive accumulation and death of cells or cell injury grossly cells swollen. Microscopically: glycogen particles appear in the cytoplasm solitary or coalesce together a (alpha) particles (150-300 A) or (beta) particles in electronic microscope). ) Special stain: PAS stain +ve Best carmine stain pink 6- Mucinous degeneration: Mucin is a structure less material pale in H&E secreted from epithelium of intestine. Causes: (Catarrhal inflammation) or in some ovarian tumor when present in more amount termed epithelial mucinous degeneration. Mucoid degeneration or myxomatous degeneration formed by connective tissue fibroblast normally in umbilical cord or in subcutaneous tissue in case of thyroid deficiency (myxedema) and in C.T tumor myxoma stain pale basophilic sky appearance with criss cross arrangement of fibrils and pleomorphic fibroblast nuclei. mucoid degeneration of fat tissue, serous atrophy, gelatin material in fat tissue, stain pink due to fatty acid react with k+. End Of Lecture 2
19. 19. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 19 Lecture 3 Prof.Dr. Khalil Hassan Zenad Aljeboori Necrosis and apoptosis (Irreversible cell injury) Apoptosis: It is programmed cell death in which the relevant cell activate enzyme capable to degrading the cell own nuclear DNA and other cytoplasmic and nuclear proteins, the apoptic cell (dead) is rapidly cleared before its content have leaked out and therefore the cell death by this path way does not elicit inflammatory reaction in the host the apoptosis differ from necrosis that in: ApoptosisNecrosis 1- No still intact.1- Loss of membrane integrity. 2- No leakage.2- Leakage of cell contents. 3- No inflammatory.3- Inflammatory host reaction. Causes of apoptosis: It is physiological in nature so it is important in physiological conditions: 1. during embryogenesis (organogenesis and involution). 2. Involution of hormone dependent tissue example damage of endometrium during menstrual cycle and regression of lactating breast. 3. In proliferating cells (intestinal epithelium) maintain a constant number. 4. In the cell served their function like neutrophils in inflammation. 5. in self-reactive lymphocytes to prevent tissue destruction. 6. Cytotoxic T cells against viral infected cells or tumor cell. Microscopically: Apoptic cell appear round or oval intense cytoplasm eosinophilic condensed chromatin, fragmented (karyorrhexis) shrinkage of cells with cytoplasmic buds and fragment into apoptic bodies composed of membrane bound vesicles of cytoplasm and organells, these fragment are phagocytosed without eliciting inflammatory reaction. Necrosis: Is a local death of tissue in the living body, the process of degeneration that lead to death termed necrobiosis.
20. 20. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 21 Types of necrosis: 1.coagulative necrosis : Occur by cut blood supply(infarction) in Such necrosis the general architecture of tissue are preserved and loss of cellular details, firm in texture , pale. Microscopically: homogeneous cytoplasm, eosinophilic and nuclear changes, pyknosis, karyolysis and karyorrhexis, coagulative necrosis or ischemic necrosis termed. The necrotic cell either removed by leukocytes or digested by leukocytes lysosomal enzymes. 2. Liquefactive necrosis: In which complete digestion of dead cells and tissue leaving liquid mass enclosed within cystic cavity. Liquefaction necrosis occur by two ways: A.Focal pyogenic bacterial infection with pus production (abscess). B.Ischemic destruction of brain tissue leaving a cavity filled with fluid, edema. 3. Caseous necrosis: Occur in tuberculosis with production cheesy like material in the center of tubercles. Microscopically :The caseation appear as amorphous granular mass, complete loss of tissue structure and cellular details, the necrotic area surrounded by inflammatory cellular reaction forming granuloma . 4. Fat necrosis : This occur in acute pancreatitis in which pancreatic lipase lysis fat cells of pancreas and peritoneum, then the triglycerides split into fatty acids combine with Ca++ give violet colour, with K+pink colour,with Na+blue colour Microscopically: Grossly white chalky material, it occur also in female breast following trauma (traumatic fat necrosis), the dead fatty tissue become soapy material like in the necrotic fatty area. 5. Gangrenous necrosis : It is not a distinctive pattern of cell death , the term still use clinically, it occur in limbs , lower legs following cut blood supply , under going into coagulative necrosis (dry gangrene )when infected by bacteria modify into liquefactive action of bacteria and attract leukocytes become wet gangrene with gas bubbles production . Moist gangreneDry gangrene 1. In enriched blood supply organs lung and intestine. 1. In ill blood supply organs limb, hands. 2. Not prominent inflammation zone.2. Prominent inflammatory zone. 3. Putrefied odor more3. Less putrefied odor. 4. Too much gas bubbles.4. Less gas bubbles.
21. 21. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 21 6. Fibrinoid necrosis: Seen in the immune response involving blood vessels, deposition of immune complexes with fibrin leakage from B.V. result in bright pink of amorphous material this type appear in polyarteritis nodosa. The leakage of proteins from dead cells result into for examples cardiac muscles fibers give creatinine kinase, troponine, liver cells give GOT, GPT and ALK phosphatase. Fate of necrosis: A. Liquefaction, removed by blood, lymph. B. Liquefaction, cyst formation. C. Liquefaction abscess formation. D. Sloughing, desquamation. E. Replacement by scar tissue. F. Calcification. G. gangrene, necrosis invaded by saprophytic bacteria (Dry and moist gangrene). End Of Lecture 3 AutolysisNecrosis 1. All dead tissue.1. Presence of dead tissue and living tissue. 2. Only dead tissue.2. Dead tissue accompanied by inflammatory reaction. 3. All RBCs lysed.3. Congestion and RBCs living.
22. 22. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 22 Lecture 4 Prof.Dr. Khalil Hassan Zenad Aljeboori Disturbances of Pigmentation Pigment are colored substance either Exogenous or Endogenous. Exogenous pigments: 1. Carbon in coal dust, air pollutant when inhaled by phagocytes (macrophages) (alveolar macrophages) to regional lymph node and in pulmonary parenchyma (anthracosis) in excessive amount cause coal workers pneumoconiosis. 2. Tattooing: form of pigment (tattoos pigment) in skin by needle or by sharp instrument. Endogenous pigments: 1. Lipofuscin or wear tear pigment: brown yellow granules intracellularly accumulated in heart, liver and brain, this pigment composed of lipid and protein derived peroxidation of unsaturated lipid of body during starvation , malnutrition = brown atrophy. 2. Melanin :Endogenous pigment brown black induced by catalyzed oxidation of tyrosine to dihyroxyphenylalnine, it form in melanocytes located in epidermis protect the body against ultraviolet radiation, absence of melamine termed albinism, in melanoma , nevus and freckles the melanine deposited due to focal melanoblasts proliferation . 3- Hemosiderin :Is brown pigment of red cells in which hemoglobin break down in too much amount the pigment contain iron either free or phagocytosed macrophages, also appear in case hemorrhagic anemia , blood transfusion and passive congestion, the pigment occur in different organs , in case of increase absorption of high iron diet . ( when excessive hemosiderin which more extensive accumulation of iron are seen in hereditary hematochromatosis in skin and viscera in which tissue injury, fibrosis, heart failure and diabetes mellitus occur) . Ochronosis: Melanine pigment affected the cartilage, of ear, nose, and may be congenitally. Bilirubin: Is the pigment of bile derived from Hb but unlike hemosiderin contains No iron. In hepatocytes changed into bilirubin, jaundice occur when too much bilirubin resulted from extensive lysis of RBCs or damage of hepatocytes or obstruction of bile ducts.
23. 23. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 23 Hematoidin: Is close to bilirubin formed in tissue from Hb like hemosiderin its formation is intracellular but need several days to occur in lacking O2 tissue, in dead tissue usually occur. Hematin: When break down of blood red cells is formed by direct action of acids or alkalies on Hb, is not precursor for hemosiderin or bilirubin . Malarial of pigment: Like hematin effect parasite on RBcs, Hb. Disturbances of minerals Calcification: Characterized by abnormal deposition of calcium salts mainly in the dead tissue it is present in 2 type: 1. Dystrophic calcification: occur in dead tissues, grossly chalky like materials and gritty sound during cutting. Microscopically: intra and extra cellular basophilic deposits, plates like 2. Metastatic calcification: Seen in cases of hypercalcemia due to: A. Increase level of parathyroid hormone. B. Destruction of bone example in Paget's disease in which bone turnover occurred. C. Vitamin D disorders or intoxication. D. Renal failure. Metastatic calcification occur through all body organs. Gout: Is the deposition of crystals ofuric acid and urates in cartilaginous, ligament about joints, synovial membrane and viscera. Such as heart valves, kidney, the uric acid and urates may deposited in kidney collecting tubules or in renal cortex form granuloma. Uric acid derived from nucleoproteins of food, when the disturbance of purine metabolism uric and urates were deposited. End Of Lecture 4
24. 24. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 24 Lecture 5 Prof.Dr.Khalil Hassan Zenad Aljeboori Inflammation Is a local tissue reaction, changes against injury or irritation.ie is progressive reaction followed by healing and repair. Causes: 1- Microbial infections. Bacteria..etc. 2- Physical against. Radiations, trauma. 3- chemicals, drugs, toxins. 4- Immunological reaction. Purpose of inflammation and the inflammatory exudates. 1- destroy injurious agents. 2- wall off injurious agents. 3- stimulate the immune response. 4- promote healing. Clinical signs or hallmarks of inflammation: 1- Redness (rubor). 2- Heat (calor). 3- Pain (dolor). 4- Swelling (Tumor). 5- Loss of function. Exudates or exudation: Is escape of fluid, protein, blood, cells from blood vessels into tissue surrounded. Transludate (non inflammatory edema): Escape of fluid only from the blood such us in case of heart failure. Exudates Transudate 1- 1- Protein ,RBCS, WBCS ,fibrin. 1-watery fluid. 2- 2- Acidic PH. 2-Alkaline PH. 3- 3- Putrefied odor. 3-odourless. 4- 4- associated with inflammatory process. 4-without inflammation occurs. 5- 5- protein 4% more 5-protein 4% less 6- 6- specific gravity 1.017 more 6- 1.017 less
25. 25. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 25 Inflammation has 4 major mechanism components or vascular reactions, changes: 1- Vasodilation of B.V and increase blood flow. 2- Increase vascular permeability and reduce blood flow. 3- emigration and activation of leukocytes and increase their phagocytic activity. 4- Chemotaxis. Attract leukocytes to site of inflammation. Major important mediator of inflammation: 1- Vasoactive amines. Such as A) Histamine. B) Serotonin (5-hydroxy tryptamine). 2- Plasma proteins. a) Complement system protein C3a, C5a, enhance vascular permeability and chemotaxis respectively. b) Kinine system in which prekallikrein changed into kallikrein, converts C5 into C5a and C5b (chemotactic mediator). c) Clotting system in which thrombin generate insoluble fibrin clot bind to platelets RBCS, WBCS form clot then followed by plasmin lysis the clot and increase vascular permeability. 3- Phospholipids derived mediators: a) Arachidonic acid metabolites: prostaglandin, leukotriene and lipases mediate all steps of inflammation. b) Platelets activating factors cause vasoconstriction and increase leukocytes adhesions. 4- Cytokines and chemokines, tumor necrosis factor (TNF) and interleukin1(IL1). Their role in inflammation during the a) Enhance cell adhesions (endothelia). b) Enhance the thrombogenicity of endothelia. c) Enhance acute phase protein. d) 1L8 interleukin 8 important for chemotaxis of neutrophils. 5- Nitric oxide (NO) is a potent vasodilator for B.V. 6-lysosomes of leukocytes those enzyme activity to degrade bacteria and tissue debris with in phagocytes and other extracellular components collagen, fibrin, elastin. 7-oxygen derived free radicals (H2O2, O2, HO) to destroy phagocytosed microbe, damage tissue, fluid, Serum, host cells possess anti-oxidant activity against these free radicals.
26. 26. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 26 8- Neuropeptides: play a role in initiation and propagation of inflammatory response during the increase vascular permeability and regulation blood pressure. Types of inflammation: Classify: 1- According to duration: a) Per acute infl. occur within 18 hrs. b) Acute infl. occur within few days c) Subacute infl. occur within 7_14th days d) Chronic inflammation occur within 14days to months, years. 2- According to exudates Type of inflammatory cells and protein exudate. 1-Serous inflammation: in which fluid enriched with protein containing few inflammatory cells mainly neutrophils, these serous fluid appear directly in early influenza infection. 2-fibrinous inflammation: Abundant fibrin in the exudate together with neutrophils and RBCS in this type of inflammation damage to B.V. occur by toxins of bacteria such as in diphtheria. 3-Hemorrhagic inflammation: in with large amount of RBCS with inflammatory cells (neutrophils) such as in anthrax, plague. 4-Purulent (suppurtive) inflammation: in which exudate composed of pus (consisting of the neutrophils (dead and living) and necrotic tissue debris with RBCS. This type caused by pyogenic bacteria (staph, strept. Corynebacterium, pseudomonas). Supportive inflammation may be occur on the surface of tissue lead to: 1. Ulcer in which loss of continuity of the surface of skin, or mucosa, due to surrounding suppurative exudate. 2. Abscess localized pus accumulated in solid tissue encapsulated by fibrous tissue if become chronic. Or may be spread the pus into blood vessels with bacteria cause pyemia or small abscess in skin called boil or furuncles or wide abscessation in skin (carbuncles) giving discharge at several points. *phlegmonous inflammation (cellulitis) diffuse abscessation spread through subcutaneous tissue.
27. 27. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 27 5- Catarrhal inflammation: superficial inflammation of mucous membrane it is commonly in infection of upper respiratory tract and intestine (in case food poisoning, parasitic infection). 6- Necrotizing or pseudo membranous inflammation: occur by powerful necrotizing agent such as diphtheria, irritant gasses, bacillary dysentery in which the necrotic pseudodiphtheric membrane occur in intestinal mucosa. 7- Allergic inflammation: in which eosinophils and much fluid and necrosis such as arthus reaction occur by when antigen injected into skin of previously sensitized individual to the same antigen or microbial agent. Prognosis or results of acute inflammation: 1- Resolution, or healing by fibrosis. 2- Spread and generalization of inflammation. 3- Become chronic. B) Chronic inflammation: May be the result of acute inflammation or may start with low virulence organism early and divided into; 1- Chronic nonspecific inflammation in which mixture of mononuclear cells seen (lymphocytes, macrophage and plasma cells) is the predominant cells type with fibroblasts. 2- Chronic specific inflammation in which mixture of cells present(occur in T.B. or syphilis), the cells include; 1) Lymphocytes. 2) Macrophages. 3) Plasma cells. 4) Basophils (become mast cells). 5) Eosinophils (when parasitic or allergic infection). *Macrophages or Histiocytes when fusion together formed giant cells against foreign body, foreign body giant cells or langhans giant cells against T.B (tubercle bacilli) in which nuclei arranged at the periphery and centrally located cytoplasm giving picture like horse shoe appearance. 6) Fibroblasts is connective tissue cells proliferated gradually and replace the inflammatory cellular reaction also enclosing the chronic state of inflammation such as pus or tubercle granuloma.
28. 28. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 28 Granuloma: A variety of chronic specific infection in a sort of mass consisting of mononuclear cells aggregation, giant epithelipoid cells and outside fibrous tissue encapsulation with the central caseous necrosis in advance stage granuloma divided into either; 1- infective granuloma caused by (Immune granuloma) Bacteria such as T.B, fungi. Spirochete. viruses, protozoa, Helminths components egg, larvae. 2- Non infective granuloma due to regional ileitis (Chrons disease) or sarcoidosis or foreign bodies. Systemic effects of inflammation: Include clinical and pathological changes. 1-Fever in response to pyrogens that act by prostaglandin. 2- Acute phase proteins. a) C-reactive protein (CRP). b) Fibrinogen. c) Serum amyloid A protein (SAA) both CRP and SAA act as opsonins around bacterial cells and fix complement. 3-Leukocytosis may reach into 40,000 IuL or even 100,000 IUL with leukemoid like reaction such Leukocytosis may be due to neutrophilia with bacterial Infection, lymphocytosis with viral infection and eosinophilia with allergic or parasitic manifestation. Certain infections such as typhoid fever, viruses, rickettsia and protozoa associated with leucopenia. 4-other manifestation of infection. Increase pulse and blood pressure 5-Disseminated intravascular coagulation and septic shock due to too much microbial agent their lipopolysaccharides enhance tumor necrosis factor and interleukin-1 both responsible for endothelial damage and intra vascular coagulation C inhibition of natural anticoagulant activity and shock resulted. Consequence of excessive inflammation action: 1- Cancer example chronic uncreative colitis. 2- Atherosclerosis. 3- Ischemic heart disease 4- Some neurodegenerative disease such as Alzheimer disease. End Of Lecture 5
29. 29. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 29 Lecture 6 Prof.Dr.Khalil Hassan Zenad Aljeboori Tissue repair, healing and regeneration Regeneration : complete reinstitution of damage component of the affected tissue i.e. tissue return to a normal state ,the most specialized tissue such as neurons of central nervous system and myocardium not regenerated, whereas ,liver , connective tissue surface epith of skin regenerate easily. Physiological regeneration that occurs in RBCS and skin surface epithelia. Repair : restoration of tissue structure and function after injury this occur by regeneration andor healing which proliferation of various cells and close intercellular spaces by matrix Healing: a reparative process in which laying down connective tissue (fibrous tissue) that result in scar tissue formation this occur when: 1- Injured area are in capable for complete regeneration(wound is much wide). 2- The supporting structures are severely damaged. Healing of cutaneous wound can occur by first intention and second intention. A)Healing by first intention : In which healing of a clean uninfected surgical wound focal disruption of epithelial basement membrane continuity and death of few cells (epithelia) and fibroblasts. Epithelial regeneration predominates over fibrosis from edges, a small scar is formed and mild wound contraction, such type of wound healing united within 2 weeks and dense scar tissue laid down within 1 month. Stages of wound healing by first intention 1- Fibrin clotted blood fill narrow wound incision. 2- Within 24 hrs. Neutrophils migrate to word the fibrin clot. 3- Within 24-48 hrs. epithelial migration from edges along the dermis. 4- By day 3 neutrophils replaced by macrophages and granulation tissue invade the incision space granulation tissue composed of new capillaries and proliferated fibroblasts. 5- By 5th day neovascularization reach its peak as granulation tissue fill the incisional space. 6- During 2nd week collagen accumulation, fibrosis proliferation that bridge the incision.
30. 30. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 31 7- Processes of blanching begins accomplished by collagen deposition and regress of vascular channels. 8- By the end of first month the connective tissue scar devoid inflammatory cells, covered by normal epidermis. B) Healing by second intention: This occur when wound edges are widely separated, the gab cannot bridged directly. Here is extensive loss of epithelia, sever wound contamination and sub epithelial tissue damage so healing occur by granulation tissue from the bottom to the surface of wound .the larger defect is greater mass of scar tissue than healing by first intention, such scarring result too much wound contraction, the mode of healing in 2nd intention occur in large wound, abscess ulcerations, and after infarction. Secondary healing differs from primary by 1- Large clot enriched in fibrin and fibronectin form at the surface of wound. 2- Inflammation more intense because more tissue defects occurred. 3- Much larger amount of granulation tissue result in greater scar formation. 4- Associated with wound contraction. Factors affecting wound healing 1-Local: 1- Wound sepsis. 2- Poor blood supply. 3- Wound tension. 4- Foreign bodies. 5- Previous irradiation. 6- Poor technique. 2-systemic: 1- Nutritional deficiencies 2- Systemic diseases , D.M 3- Therapeutic agents 4- Age. End Of Lecture 6
31. 31. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 31 Lecture 7 Prof.Dr.Khalil Hassan Zenad Aljeboori Cellular adaptation and disturbances of growth Adaptation: Are reversible change in tissue either physiological like enlargement of uterus or breast during pregnancy or due disease conditions. 1. Hypertrophy: increase in size of cells resulted into increase in the size of the whole organ maybe: A. Physiological: like hypertrophy of skeletal muscle in athletes or workers, or uterus during pregnancy. B. Pathological like cardiomegaly secondary to hypertension. The adaption can progress to dysfunction if the stress or cause is not relieved. 2. Atrophy: shrinkage of cell size by loss of cell substance this opposite to hypertrophy, when more cells involved lead to reduce the size of organ. Causes: A. Decrease work load examples: immobilization of limbs. B. Denervation as in poliomyelitis. C. Decrease blood supply. D. inadequate nutrition. E. Loss of endocrine stimulation, example: post-menopausal endometrial atrophy. 3. Hyperplasia: Increase in the number of cells, randomly proliferation of cells under different stimuli. A. Physiological hyperplasia proliferation of glandular epithelial of breast during pregnancy and enlargement of uterus during pregnancy. B. Compensatory hyperplasia occur when part of tissue is removed, the other part of tissue proliferate to restore the normal size of the organ like liver. Most of pathological hyperplasia caused by excessive hormonal and growth factor, example excessive estrogen stimulation lead to endometrial hyperplasia and papilloma virus in skin cause squamous cells hyperplasia, if the cause hormone or growth factor or virus are subsided the hyperplasia disappear if the cause not subsided and continued the hyperplasia develop into cancer .
32. 32. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 32 4. Metaplasia: Reversible change in which the mature adult cell (epith or mesenchymal cell) replaced by another relative cell type, example: ciliated columnar epithelium of trachea, bronchi replaced squamous epithelium in smoking. The metaplastic epithelium still survive the protective mechanism such as cilia and mucus production. Also if the cause example smoking is persisting the metaplasia predispose into malignant transformation such squamous cell carcinoma in bronchi in heavy smokers, also in urinary bladder in schistosomiasis squamous metaplasia occur,if persists may develop to cancer. Closely related topic to metaplasia is the process of dysplasia which is the definite step in cancer evolution. Dysplasia: A disordered growth in mucus membrane like cervix, does not progress to cancer, dysplastic cells showed pleomorphic, hyperchromatic and show abundant mitotic figure, mild or moderate dysplasia is reversible but diffuse dysplasia become cancer. Anaplasia: Loss of normal cellular differentiation or organization i.e. cells become primitive, embryonic and undifferentiated type, this important feature of tumor cell. Anaplasia = Malignant Neoplasia = tumor End Of Lecture 7
33. 33. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 33 Lecture 8 Prof.Dr.Khalil Hassan Zenad Aljeboori The Infectious Disease I Commensals: microorganism live on expense of the host without harm like: a- Bacteria of skin b- VIT K producing bacteria. Pathogens: microorganism that injure the host, cause disease. Pathogenicity: ability of microbe to cause disease. Virulence: degree of Pathogenicity. Opportunistic infection : microbe live in the body, but cause disease and become pathogenic when depressed immunity in aids or microbe present in abnormal site in body like E .coli normal flora in intestine but become pathogenic when introduced in urinary tract other example streptococcus viridians in mouth during tooth extraction may reach valves of heart and cause endocarditis . Infection : Presence of microbe in a part of body (normally absent). The microbe multiply, stimulate the host response and cause the disease. Defenses mechanism : 1- Nonspecific defense mechanism a- Mechanical barriers example skin, mucosal layer of respiratory and GIT mucosa, conjunctive. b- Glandular secretion : Acidity of sweat, gastric acid, lysozyme enzymes secreted by mucous membrane, secretory IgA (antiseptic paint). c- Secretions currents Continuous secretions of tears, ciliated epith. Of respiratory system, obstruction of urine flow, lacrimal gland, saliva .etc. d- Phagocytosis by neutrophils and macrophages both migrate to microbial agent and ingulf it. *inflammation and complement system are nonspecific defense.
34. 34. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 34 2- Specific defense mechanism: Immunity: a- Humoral immunity in which production of antibodies against microbial agents when extracellular appearance in body tissue. b- Cell mediated immunity:In which production of Lymphokines, Monokines, chemokines against intracellular microbial agent such as T.B, viral infected cell and cancer cell. How infections agents cause disease 1- Microbe can contact or enter the host cell like T.B , cause cell damage 2- Pathogens can release a- Endotoxins by Gram negative bacteria or exotoxin by Gram positive bacteria that kill the host cells. b- Release enzymes that cause tissue damage. c- Damage of tissue by ischemia. 3- Pathogens induce cell response that mediated tissue damage by immune mediated mechanisms. Mechanism of virus damage to cells 1- Inhibit the host cell DNA ,RNA or proteins synthesis like polio virus 2- Virus proteins inserted in host cells and cause damage the cell or promote cell fusion like in measles , HIV ,herpes virus 3- Virus replicate in cells cause cell lysis like polio virus. 4- Virus protein on the surface of host cells enhance immune response against virus infected cell, cause liver failure such as in hepatitis virus. 5- Virus damage defense mechanism lead to secondary infections by bacteria (Strept. Pneumoniae) like in influenza virus. 6- Virus kill one type of cells and cause damage to other cells poliovirus lead to muscular atrophy. 7- Virus cause cell proliferation transformation lead to cancer hepatitis virus, EB virus. Mechanism of bacterial injury, and damage to tissue 1- Adhere and enter the cells cause lysis such as T.B 2- Release endotoxin polysaccharide produced by Gram negative bacteria include; a- Include fever. b- Septic shock c- Respiratory distress syndrome. 3- Release of exotoxin protein induced by Gram positive bacteria such as; a- Diphtheria toxin by coryn. diphtheria cause heart failure and neural defects. b- Tetanospasmin by clostridium tetani cause tetanus.
35. 35. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 35 Immune evasion by microbes: Microbe escape HI and CMI BY 1- Kept and residing in host cells. 2- Cleave antibodies such as gonococcus cleave IgA. 3- Resist complement mediated lysis. 4- Survive in phagocytic cells such as T.B 5- Varying or shedding antigen, continuously each time specific Ag. 6- Cause immune suppression. End Of Lecture 8
36. 36. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 36 Lecture 9 Prof.Dr.Khalil Hassan Zenad Aljeboori The Infectious Disease II Some human infectious diseases. Viral diseases: Rhinoviruses and influenza viruses: Responsible for common cold , both RNA viruses type A,B,C, both types caused pandemic infection 1918, it contain both hemagglutinin and neuraminidase mutation of these protein resulted in to escape of virus from the antibodies (antigenic drift) Avian influenza (bird flu) H5N1 cause massive outbreak in poultry and jump to human and cause outbreak. An outbreak at 2009 in virus H1N1 an epidemic of a new strain referred to as swine flu.The resulted mutation of (4) strains of influenza virus A H1N1 an endemic in human and endemic in birds and two endemic in pigs in both the rhinitis , sinusitis , otitis media , Pharyngitis, tonsillitis , tracheitis , bronchitis , bronchiolitis , and secondary bacterial infection by strept. Pneumonia. Herpes viruses infections Herpes virus DNA, HSV-1, HSV2 neurotropic virus , replicate in skin and mucous membranes at the site of entrance of virus ( oropharynx or genitalia ) cause vesicular lesions and infect neuron of the location . The virus remain in nerve cells latent and reactivate and infect skin and mucous membrane. Cells form multinucleated syncytia containing inclusion of virus particles diagnostic in smear of the blisters fluid .so the viral infection clinically show fever blisters (cold sore). Intraepithelial vesicle (hydropic degeneration) of skin around the lips, nose, burst, crust formation at the vesicles. The forms of viral infection include; 1- Gingivostomatitis. Vesicles in mouth, tongue, pharynx. (HSV-1). 2- Genital herpes vesicles seen at genital mucosal layer and external genitalia, associated with ulceration and rimmed by inflammation (HSV-1,2) neonates will affected during delivery in neonates , splenomegaly liver lesion , lymphadenopathy, CNS lesion . 3- Herpetic eye infection: A-Herpes epithelial keratitis lysis of corneal epith. B- Herpes stromal keratitis due to immunological reaction to viral infection. 4-other herpetic infections:Herpes encephalitis, Kaposi sarcoma, eczema Herpeticum, herpes Esophagitis, Bronchopneumonia and hepatitis.
37. 37. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 37 Bacterial infections: Hemophilus influenza : Gram negative bacteria cause lower respiratory tract infection and meningitis. So there is pharyngitis sinusitis, laryngitis, otitis media. Bronchitis especially complicate viral respiratory tract infection obstruction of air ways by fibrin rich exudate similar to strept. Pneumonia infection. H. influenza also produce suppurative meningitis in children. Tuberculosis : Mycobacterium tuberculosis and M. bovis kill 3million patient each year M. tuberculosis transmitted by inhalation mainly, M.bovis is transmitted by milk as for M. avium and M.intracellurar cause infecting in aids patients. M. leprae is the cause of leprosy. Pathogenesis of T.B. depend on 1- Virulence of bacteria. 2- Relationship of hypersensitivity to immunity. 3- Infection degree. So T.B give no toxins ,no endotoxin and no histolytic enzymes but enter macrophages and cause delayed type of hypersensitivity in which macrophages secrete TNF- which cause tissue damage and fever. DTH reaction cause destruction of tissue initially nonspecific reaction by mononuclear cells (lymphocytes macrophages . plasma cells )and few neutrophils then by 2-3 weeks developed in to granuloma with caseous necrosis at the center forming typical tubercle .the host response depend on either the primary infection (first exposure to T.B or 2nd exposure (previous infection ) the role of interferon gamma (INF-) secreted by sensitized lymphocytes (CD4+ ), and activate the macrophages for phagocytic activity to kill T.B and cause tissue damage . Primary T.B When inhaled T.B in to the lung phagocytosis by alveolar macrophages the T.B still multiply and lyse macrophages and enter new cells which transport T.B to hilar lymph node during few weeks, the granuloma developed with central necrosis . this under effect of (INF-) released by CD4+ cells and granuloma developed under effect of (INF-) and TNF- which cause activation of macrophages ,and later on tissue damage .(caseation) followed by calcification in lung and hilar lymph node termed Ghon complex. Secondary and disseminated T.B this occur when reinfection or reactivation of dormant bacilli from primary infection when too much virulence of bacilli or patient susceptible to infection (low immunity ) also disseminated T.B in blood circulation , lymphatic and cause caseation and granuloma in kindly lungs , meninges, bone marrow and other organs. The caseation may followed by cavitation and T.B reach blood circulation and cause military T.B in various organs.
38. 38. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 38 Leprosy (Hansen disease) Caused by M. leprae infect skin and peripheral nerve it transmitted through inhalation taken by alveolar macrophage, through blood reach skin and peripheral organs. Pathological features : 1- Tuberculosis leprosy when high cellular immunity tuberculuid leprosy and epithelioid granuloma in skin localized flat red in colour with induration ,depressed center , Nerve when affected lead to atrophy in skin and muscles when trauma , this part were ulcerated ,contraction , microscopically, epithelioid granuloma , giant cells. Lymphocytes (CD4, CD8) aggregation. 2- Lepromatous leprosy Involve skin, nerves, eye, testes, hand, feet no infection in vital organ brain. Because high temp. More than in peripheral organs. The lesions began macules papules or nodular lesion, coalesce of lesion give a lion facies .in nerve lead to loss of sensation in feet, hand. Microscopically Macrophages laden with bacilli (AFB) some time in liver, lymph node, spleen. In advanced cases in testes cause destruction and erythema nudosumvasculitis. Lepromin test like T.B by injection of lepromin Ag M.leprae Pyogenic bacteria. Staph epidermidis : cause opportunistic infection in catheterized patients, prosthetic valves , drug addicts Staph aureus : Causes: boil, carbuncles in skin, pharyngitis, pneumonia, endocarditis, food poisoning, infections of burn, surgical wound infections, toxic shock syndrome. virulence factors include 1- Protein surface protein help bacteria to attach to tissue. 2- Lytic enzymes , proteases ,lipase. 3- Toxins include hemolytic, leucocidin enterotoxin, hemolytic toxins, exfoliation toxin associated with scaled skin syndrome. Toxic shock syndrome toxin. Streptococcal infection : Associated with pharyngitis, scarlet fever, erysipelas, impetigo (infection of superficial epidermis) rheumatic fever, and glomerulonephritis. In mouth strept. Viridanse endocarditis In mouth strept.Mutans dental caries Strep. Faecalis (enterococcus faecalis) UTI and endocarditis Strep. Agalactiae UTI, neonatal sepsis, meningitis.
39. 39. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 39 Virulence: 1- M protein prevent phagocytosis 2- C5a peptidase (degrade C5a ) 3- Surface molecules (protein ) to attach to host extracellular matrix 4- Polysaccharides inhibit phagocytosis 5- Pneumolysin activate classical pathway lysis target cells 6- Pyogenic exotoxin cause fever rash 7- Metabolism of sucrose in to lactic acid by Strept.Mutans cause demineralization of tooth, plaque, caries formation. 8- Anti strept M protein antibodies cause cross react with cardiac myosin lead to rheumatic fever. Gastrointestinal infection : occurred when host defenses were weakened 1- Low gastric acidity. 2- Antibiotic. 3- Decrease peristalsis movement. 4- Mechanical obstruction. Enteropathogenic bacteria cause disease by: 1- Production of enterotoxins it cause food poisoning e.g. S. typhimurium. 2- Exotoxin by E.coli , vibrio cholera cause intestinal damage , secrete too much water. 3- Invasion of mucosal layer by shigella, dysentria , salmonella cause hemorrhage ,ulceration. 4- S. typhi cause damage mucosal layer to peyer, s patches and to blood stream causing enteric fever. Normal defense in GIT: 1- Acidic ph. gastric juice. 2- Mucus layer covering the gut epith. 3- Pancreatic and bile salts lyse microbial agents. 4- IgA (Anti septic paint) and M cells modified epith. Cover mucosal associate lymphoid tissue take the pathogen to MAIT area to destroy bacteria. 5- Bacterial flora inhibit pathogens establishment. Helicobacter pylori : Causes: 1) Chronic superficial gastritis. 2) Chronic atrophic gastritis. 3) Carcinoma of the stomach, and sometimes lymphoma when reactive, invasion of B and T cells clones.
40. 40. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 41 Clostridial infection : Anaerobic bacteria produce the following disease: 1) Anaerobic cellulites and gas gangrene by Cl. per fringes (welchii) 2)Tetanus by Cl. tetani all these infection occurred by contaminated wound, the toxins of these bacteria (neurotoxin) potent toxin cause skeletal muscle contraction. 3) Botulism caused by Cl. botulinum in contaminated canned food, also neurotoxin released and block acetylcholine release so paralysis of muscles fibers occur. 4) Pseudo membranous colitis by Cl. difficile also release multiple toxins. Syphilis: Caused by Treponema pallidum detected by: 1- Silver stain. 2- Dark filed examination. 3- Immunofluorescence. The infection occur in 3 stages: 1) Primary stage: occur within 3 weeks, the infection in the form of firm non-tender red raised lesion (chancre), located in external genitalia composed of plasma cells, macrophages infiltrate, with obliterative endarteritis. 2) Secondary stage: occur within 2-10 weeks as a diffuse rash in palms and soles, with white oral lesion, fever, arthritis, and lymphadenopathy. 3) Tertiary stage : occur later on in years after the primary the inflammatory lesions in aorta, heart, CNS, liver, bone, skin, called gummas composed of granuloma with central necrosis surrounded by macrophage palisading with fibroblasts and outer plasma cells. Genital syphilis : The Treponema transmitted from infected mother to placenta and cause: 1) Late abortion. 2) Still birth. 3) Death of newborn. 4) Persist a latent in child life. Gonorrhea: caused by Neisseria gonorrhoeae, gram negative diplococcus their pathogenesis occur when bacteria invade epithelial cells and facultative intracellular bacteria depends on host cell actins filaments, their capsule inhibit phagocytosis, secrete protease cleave IgA and release endotoxin which give TNF- cause shock and multisystem failure.the infection by this microbe begin purulent exudates, granulation tissue formation, fibrosis in urethra with mucopurulent exudates and spread to epididymis, prostate, seminal vesicles and in chronic cases sterility occur.
41. 41. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 41 Chlamydial infection : Obligate intracellular organisms in 2 forms either elementary bodies or reticulate bodies both cause: 1-Lymphogranuloma venereum with epidermal vesicles on the genitalia then ulcerate and oozes fluid, the ulcer base, granuloma formation with stellate abscesses in the center of granuloma. 2-Inclusion conjunctivitis: in infants from mother with cervical infection caused by C.trachomatis. 3-Reiter syndrome: a combination of conjunctivitis, genital infection and polyarthritis. 4-Trachoma: kerato conjunctivitis cause blindness in poor societies and transmitted by hand contacts, flies. 5-Ornithosis: pneumonia by C. psittaci secreted from infected birds inhaled with dust particles. Diagnosis; by fluorescent antibody reaction, culture on cell culture and by PCR. Parasitic infection : Schistosomiasis, bilharziasis : Caused S. mansoni, S. hematobium and S. japonicum. Larvae penetrate skin, migrate by B. circulate to traverse the lung, reaching pelvic or portal vein. In pelvis develop into adult with egg production and granuloma develop around the egg in pelvis, bladder. Some eggs from portal vein to intestine wall depend on type of parasite with granuloma. (S.mansoni) in pelvis. Granuloma develop into carcinoma when in bladder occurred.(S.hematobium),egg in stool or urine. S.mansoni in liver when present in portal vein cause : 1- Hepatotoxic effect by egg toxin 2- Granuloma in liver mediated by TNF, H1, H2, cells. 3- TH2 secret IL, 3, 4stimulate mast cells level. 4- TH2 secrete IL5 important for eosinophils and give basic protein kill the larvae. 5- Egg stimulate the lymphocyte to give fibroblasts growth factor to form fibrosis in portal area or in other site. Complication of schistosomiasis include : 1-granuloma in liver, gut, pelvis, in the center ova present, portal fibrosis pipe stem fibrosis. 2-granulomatous pulmonary arteritis, and 3-glomerulonephritis due to Ag- Ab complexes deposition. *S.hematobium in urinary bladder cause hematuria, calcified granuloma, later on develop to carcinoma (transitional cell carcinoma) or (squamous cell carcinoma).
42. 42. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 42 Hydatid cyst : Caused by Echinococcus granulosus and sometime Echinococcus multicularis. The hexacanth embryo (larvae) hatch in intestine of intermediate host (taken contaminated food with egg). The larvae migrate to liver mainly and to the lung and other organs cause hydatid cyst enlarged gradually and cause space equipying lesion. The wall of cyst composed of germinal layer with protosolices surrounded by laminated hyalinized layer and fibrous capsule outside infiltrated with mononuclear cells, giant cells and eosinophils. Trichomoniasis : Sexually transmitted disease, protozoa flagellated, cause superficial infection in genital tract of male and female with watery fluid in vagina and itching, urethritis with mononuclear cells and neutrophils infiltration. MYCOTIC INFECTION : Aspergillosis: Associated with allergic lesions, sinusitis, pneumonia, the fungus appear branching filaments hyphae and budding spores. The fungus surface had 1) sialic acid to bind with protein matrix laminin, fibronectin. 2) Produce aflatoxins (carcinogenic). 3) had restriction and mitogillin both ribotoxin inhibit protein synthesis. 4) Allergic reaction through IgE mediated hypersensitivity, allergic alveolitis and bronchopneumonia with asthma mediated by mitogillin. 5) aspergilloma colonization of the pre-existing cavity caused by T.B ,bronchiectasia. 6) Massive aspergillosis in immunodeficient individuals with infection of all organs. Candidiasis: associated with superficial infection of oral cavity (thrush), valvovaginitis or systemic infection associated with Bronchopulmonary disease and esophagitis. Candidiasis caused by candida albicans. Sporotrichosis: caused by sporotrichiumschenkii ulceration with abscess formation in skin and subcutaneous tissue. Disease of trichophytonrubrum include Tineacorporis (Ring worm) tineapedis ( Athlet's foot). Disease include histoplasmosis, Histoplasma capsulatum and coccidiodomycosis (Coccidiodesimmitis) cryptococcusis (Cryptococcus neoformans) both associated with pneumonia and meningitis. End Of Lecture 9
43. 43. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 43 Lecture 10 Prof.Dr.Khalil Hassan Zenad Aljeboori Disturbances of body fluids and electrolytes I Fluid present in extra cellular and in intra cellular compartment the extra cellular compartment divided in to intra vascular (plasma) and in interstitial tissue. Extra cellular fluid: Chemical composition are similar for the extra cellular fluid mainly sodium, chloride, bicarbonates and low concentration of potassium, magnesium, calcium, phosphate, and sulphate ions together with few protein, glucose and urea. Blood plasma contain large amount of protein comparable to low amount in intracellular fluid. Intracellular fluid: Contain high concentration of potassium and low concentration of sodium and chloride, also it contain more phosphates, sulphate, magnesium, and protein and less bicarbonates than in extracellular fluid. Extracellular fluid Intracellular fluid More Less Na Na Bicarbonates Bicarbonates Chloride Chloride Less More Mg++, k+, Ca++ k, PO4, SO4 PO4 +++ , SO4 ++ . Protein Protein, glucose, urea Mg Fluid and electrolyte balance: In healthy individual there is balance between the amounts of water taken in to the body and that eliminated as well as normal distribution and balance of body fluid and their electrolytes. The water intake by food and drinking and leave body from kidney, skin, lung, glandular secretion A constant exchange between fluid compartments keep the water in dynamic state, depending on electrolytes and protein concentration (active osmotic particles) in fluid compartment. While exchange of substances between the plasma and interstitial fluid occurred by filtration and diffusion across the capillary endothelia, whereas water passes freely
44. 44. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 44 between the intra and extra cellular compartment in accordance with osmotic pressure relationship whereas, electrolytes do not cross the cell members. Kidney: considered important factor regulate water and electrolytes balance. Both conserve or excrete from kidney in maintaining normal volume, concentration, PH of body fluid this regulation in kidney occur by antidiuretic hormone (ADH) and adrenal cortical hormone. Dehydration : Disturbances in water balance in which output exceed the intake causing water below the normal level. As in disorder in swallowing, comatose patients. Mental patient, sweating that is in primary dehydration. Second dehydration cause by loss of sodium, and electrolytes from body during, vomiting, diarrhea, urinary loss of Na+ in Addison disease, chronic renal disease or by both from of dehydration (primary and secondary). Electrolytes disturbances: The role of electrolytes in the maintaining of osmotic pressure and preservation of acid base balance and normal neuromuscular irritability. Electrolytes also had a role in balance and distribution of body fluid among these electrolyte: Sodium: is extra cellular fluid important for extracellular fluid osmotic equilibrium, it origin from food and water and salts. Urinary output of sodium equal to the intake. The retention of sodium and water resulted in edema, this occur in congestive heart failure, hepatic cirrhosis and in nephrotic syndrome. Decrease sodium level in plasma hyponatremia: occur when retention of water more than sodium retention, so there is muscle twitching nausea, fatigability. Hypernatremia: occur when dehydration, diabetic coma, in which output of water in excess of sodium or sever restriction of water (in dehydration) also occur in case of aldosteronism. Potassium: main intracellular, important for cell metabolism and conduction of nerve impulses and for contraction of cardiac and skeletal muscles, help equilibrium between cells water and extracellular fluid. Hypokalemia occur when less K+ taken in starvation or excess loss in vomiting, diarrhea, surgical trauma, administration of adrenocortical hormone and adrenocortical activity. Pathological effects of K+ decrease in heart (foci of hyaline change) on myocardium, vacuolization of proximal convoluted tubules (PCT) in kidney and muscle paralysis.
45. 45. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 45 Hyperkalemia K+ increase rarely occur, because kidney excrete K+ when in high level. Chloride: follow the change of sodium concentration in plasma. Magnesium: intracellular concerned with carbohydrate and protein metabolism and neuromuscular conduction. Hypomagnesemia mg++ decrease occur in starvation, alcoholic, diuresis and associated with muscular twitching, coma and convulsion. Hypermagnesemia when mg++ increase occur in sever dehydration. Diabetic acidosis so there is coma, lethargy and respiratory failure. Disturbances of circulation (blood flow) Edema: excessive accumulation of fluid in tissue spaces such as in pleura termed hydrothorax, in periton (ascites) in pericardial sac (hydro pericardium). Anasarca is a generalized subcutaneous edema. Edema non inflammatory = transudate Inflammatory edema= exudate Causes of edema (transudate): 1- Increase hydrostatic pressure either localized or generalized (systemic) Localized increase in vascular pressure can result from impaired venous return example lower extremity, deep venous thrombosis can result in edema restricted to distal portion of the affected leg. Generalized increased venous pressure with resulted systemic edema occur in congestive failure with involvement of right ventricular cardiac function together with reduced renal perfusion resulted in renal fluid retention and edema with increase venous pressure heart. 2- Reduced plasma osmotic pressure: This occurred when loss of albumin and plasma protein form circulation in case of nephrotic syndrome so decrease colloidal osmotic pressure which mainly depend on albumin also decrease albumin synthesis in liver disease (cirrhosis ) and malnutrition (poor protein) , in all these cases (reduced osmotic pressure) lead to movement of fluid in to interstitial spaces accompanied by renal hypo perfusion together with trigger the renin-angiotensin aldosterone axis induced to much water and salt retention by secondary aldosteronism similar in heart failure .
46. 46. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 46 3- Lymphatic obstruction: Impaired lymphatic drainage result in localized edema like elephantiasis (caused by wucheriabancrofti-their filarial close the lymphatic system of lower limbs and genitalia resulted in edema (lymphedema) . cancer of breast cause loss of lymphatic drainage so upper limb edema similarly in breast carcinoma obstruction of the superficial lymphatics cause edema of overlying skin (lymphedema). 4- Sodium and water retention. Increase of salts with water obligate cause increase hydrostatic pressure due to expansion of intravascular volume with reduced vascular osmotic pressure. Salt retention occur with impairment renal function such as in post streptococcal glomerulonephritis and acute renal failure. Pathological features of edema: 1) Subcutaneous edema: This can be diffuse in regions with high hydrostatic pressure such as 1-In gravity termed dependent edema with gravity. Distribution involving the leg when standing for long time, sacrum when recumbancy, dependent edema is a feature of cardiac failure of right side. 2-Edema due to renal dysfunction or nephrotic syndrome, affect all parts in body equally it is more sever than cardiac edema, all organs affected such as in eyelid periorbital edema. In any part of body finger pressure leave finger shaped depression so called pitting edema. 2) Pulmonary edema : Occur with the following: 1- Left ventricular failure. 2- Renal failure. 3- Acute respiratory distress syndrome. 4- Pulmonary infection. 5- Hypersensitivity reaction. Gross lung, heavy, frothy fluid blood tinged. Microscopically alveolar spaces fluid with fluid (pale pink), congestion of alveolar capillaries. 3) Brain edema: Localized with infarction, abscesses, tumor Generalized in encephalitis or with obstruction of brain venous out flow, trauma cause localized or generalized depend on extent of injury brain appear swollen, flattened gyri.
47. 47. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 47 Clinical significance of edema Subcutaneous edema indicate renal and cardiac failure it is harmful effect. Pulmonary edema: death due to abnormal respiration function. Brain edema: fatal rapidly. Hyperemia and congestion: Local increased volume of blood in particular tissue. Hyperemia: is active process resulted from augmented blood flow due to arterial dilation example in skeletal muscle during Practice or flushing Physiological hyperemia in which affected part more red because engorgement of arterial oxygenated blood, also with acute inflammation . Congestion: passive process resulted from low venous return out of tissue it may occur systemically as in cardiac failure or locally resulted from local venous obstruction. The affected organ blue red colour (cyanosis) due to deoxygenated blood in affected tissue. Congestion of capillary closely related to edema so both occur together long standing congestion called chronic passive congestion which due to deoxygenated blood cause hypoxia and degeneration and death of parenchymal cells. Subsequent fibrosis capillary rupture at this site cause lysis of RBCS and hemosiderin engulfing by macrophages (hemosiderin laden macrophages). Grossly- cut section oozing blood, red of affected site. Microscopically: In acute pulmonary edema congestion of alveolar capillaries with alveolar edema and hemorrhage In chronic cases septae, alveolar wall thickened, fibrotic and alveolar spaces filled with hemosiderin laden macrophages (heart failure cells) with edema. C.V.C in lung termed brown induration. In liver : In acute congestion: central vein and sinusoids distended with blood. With degeneration of central hepatocytes the peripheral hepatocytes better oxygenated because still receive oxygenated blood from arterioles. In chronic venous congestion (CVC) : Grossly: liver enlarged oozing blood in cut section, the central region of liver red, congested, the surrounding region in hepatic lobule uncongested, tan, sometime fatty liver (nutmeg liver).
48. 48. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 48 Microscopically: Center lobular necrosis, hemorrhage, hemosiderin laden macrophages and hepatic fibrosis with long standing heart failure. Causes of CVC: 1) Cardiac valves defect. 2) Cirrhosis. 3) Obstruction of large blood vessel. 4) Age. 5) Pregnancy. Hemorrhage: Extravasation of blood from vessels into extravascular space. Capillary bleeding and hemorrhagic diathesis occur in chronic congestion and wide variety of clinical disorders both two cases hemorrhage by diapedesis. Hemorrhage by rhexis when damage of artery by trauma, atherosclerosis, aneurysmal dilation, inflammatory or neoplastic- erosion of vessel wall. Types of hemorrhage: 1- Petechial H. with 1-2 mm pin point, in skin, mucosal surface, serosa occur with: 1. Increase intravascular pressure locally. 2. Low platelets count (thrombocytopenia). 3. Defect in platelets function. 4. Clotting factor deficiency. 2- Purpura: H. with 3-5mm width similar to petechial H. causes and with trauma, vasculitis (infl. Of B.V). 3- Ecchymosis. H. with 1-2cm. wide area of hemorrhage, associated with hemosiderosis. 4- Hematoma: wide localized area of blood accumulation in body following trauma, similar to ecchymosis lysis of red cells, hemosiderin in engulfed macrophages appear. Large accumulation of blood in the thorax = hemothrax, in pericardium= hemopericardium , in periton =hemoperitoneum . End of Lecture 10
49. 49. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 49 Lecture 11 Prof.Dr. Khalil Hassan Zenad Aljeboori Disturbances of body fluids and electrolytes II Ischemia Decrease of oxygenated blood flow in tissue due to contraction or constriction of vessels (arterioles) due to: 1- Spasm of small blood vessels. 2- Arterial wall defect (arteriosclerosis). 3- External pressure on vessels (tumor, abscess,). 4- Blockage of lumen by thrombus or emboli. Sudden ischemia cause coagulative necrosis and infarction, and gangrene. Thrombosis: Coagulation of blood within blood vessels during life. The pathological form of hemostasis is thrombosis. Both hemostasis and thrombosis involve three component. 1- Vascular wall. 2- Platelets. 3- Coagulation cascade. Pathogenesis: 3 predisposing factor include: 1- Endothelial injury. 2- Stasis or turbulence of blood flow. 3-Blood hypercoagulability. 1- Endothelial injury: Endothelial loss can lead to thrombosis during exposing of sub endothelial extracellular matrix, adhesion of platelets. Release of tissue factor and local depletion PGL2 and plasminogen activator. Similarly the dysfunctional of pro coagulating factors platelets adhesion molecules, tissue factor, plasminogen activator inhibitors or may reduce anticoagulant effectors. Endothelial dysfunction occur in through; 1- Hypertension. 2- Turbulent flow. 3- Bacterial endotoxins. 4- Homocystinuria. 5- Hypercholesterolemia. 6- Radiations. 7- Products absorbed from cigarette smoke.
50. 50. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 51 2- Stasis and turbulence of blood flow : By both mechanisms there is: 1- Disruption luminar flow and bring platelets into contact with endothelia. 2- Prevent dilution of activating clotting factor by fresh flow blood. 3- Retard the inflow of clotting factor inhibitors and permit build up of thrombus. 4- Promote endothelial cells activation resulting in local thrombosis and leukocytes adhesions. Both mechanism (stasis and turbulence) of blood flow occur in several clinical conditions: 1- Ulcerative atherosclerotic plaque. 2- Aneurysm (local dilation) of aorta and arteries. 3- Acute myocardial infarction. 4- Mitral valve stenosis (after rheumatic heart disease). 5- Hyperviscosity syndrome, (polycythemia). 6- Deformed red cells in sickle cell anemia. 3- Hypercoagulability: (change in physical and chemical) component of blood i.e. indicate alteration of coagulation pathway that predispose to thrombosis primary (inherited) when mutation in factor V gene and prothrombin gene. The pathogenesis of secondary (acquired) hypercoagulability include: 1- Cardiac failure or trauma associated with vascular injury. 2- Oral contraceptive and pregnancy in which increase clotting factor by liver. 3- Disseminated cancer. 4- Advance age. 5- Smoking and obesity. Pathological features: 1- Thrombi can develop anywhere in cardiovascular system in cardiac chamber, valves, arteries, veins and in capillaries. 2- The size and shape of thrombi depend on site or origin and the cause. Cardiac and arterial thrombi at the site of endothelial injury whereas venous thrombi at site of flow stasis. Thrombi in the heart valves may occur following bacterial and fungal born infection cause valve damage and thrombus formation, vegetation like in infective endocarditis, also vegetation occur in non-infections state it develop in hyper coagulable state (nonbacterial thrombotic endocarditis) .
51. 51. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 51 Fate of thrombosis: 1. Propagation, additional accumulation of fibrin and platelets cause vessel obstruction. 2. Embolism when fragments of thrombus circulate in blood. 3. Dissolution of thrombus by fibrinolytic activation which lead to thrombus shrinkage and lysis of recent thrombi. 4. Organization and canalization, organization of old thrombus by endothelia, fibroblasts and smooth muscle proliferation. Occasionally instead of organization the center of thrombus may under goes enzymatic digestion by lysosomal enzymes of trapped leukocytes and platelets, this recanalization convert the thrombus into vascularized mas of connective tissue, these channels may not restore significant flow to many obstructed vessels. Embolism An emboli is some a solid or other foreign material carried in the circulation to a point different from the origin. Emboli may be composed from portions of thrombus, tumor cells, fat, air, masses of bacteria, mass of parasites. Emboli that originated in the right side of heart or in venous system it arrested in lungs if originated in portal vein it arrested in liver whereas emboli originated at the left side of heart and arteries it arrested in peripheral parts of arterial system. Veins are easily penetrated by tumor cells so tumor emboli arrested in liver and lungs. Forms of emboli: 1. Thrombo emboli: - fragmental thrombi form 99% of emboli. 2. Fat emboli: - fat droplets, injured fat tissue. 3. Air emboli: - bubbles of air during surgery, pneumothorax. 4. Atherosclerotic emboli: - (cholesterol emboli). 5. Tumor emboli-metastatic tumor cells. 6. Foreign body emboli: - as bullets or shrapnel. 7. Bone marrow emboli: - bits of bone marrow when bone fracture. Embolism from thrombus this common type 99% of emboli, their effects depend on; 1. Emboli is septic or non-infected. 2. The size of embolus. 3. The vessels in which become arrested. Pulmonary emboli which arrested in lungs and originated in venous blood and right side of heart are fatal whereas emboli that originated in cardiac chambers i.e. mural endocardial thrombosis is a complication of cardiac infarction.
52. 52. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 52 Anticoagulant drugs, heparin and dicumarol are important in management of thrombus or emboli. Septic emboli_ which contain infective microorganisms causes pyogenic or abscess in new arrested part in the body. Infected emboli from infected endocarditis, valvitis spread infection to other parts of body, infection of vein in appendicitis give septic emboli arrested in liver, with multiple abscesses formation. Infarction or gangrene may be originated from thrombus and emboli when cut oxygenated blood supply occur in these areas in internal organs or extremities. Infarction Localized area of ischemic necrosis in living tissue or organ at an end artery area so triangular in shape mostly. Infarction rarely occur in venous drainage area. Causes: 1. 99% of infarcts caused by thrombosis or emboli causing arterial obstruction. 2. Expansion of atheromatous plaque by hemorrhage. 3. Spasm of coronary artery. 4. Pressure on vessels from outside by tumor, fibrous adhesion abscess. 5. Twisting (torsion) of the loop of small intestine (volvulus), ovary testis, hernia in which viscera protruded outside the cavity. 1-Red infarction: occur with 1. With venous occlusions such as in ovarian tumor. 2. In loose tissue such as lung, intestine. 3. In tissue that had dual circulation such as lung, small intestine rare in liver because abundant circulation in liver. 4. In tissue with previous congestion, slow flow 5. When flow is reestablished to a site of previous arterial occlusion. 2-White infarction: occur with: 1. Arterial occlusions or in solid organs heart, spleen, kidney. 2. Infarct areas are wedge shape at the apex of end artery. 3. Infarct area well defined by narrow rim of congestion with inflammatory zone at the edge of lesion (line of demarcation), whereas line of demarcation non- prominent in red infarct. 4. In solid organs few extravasated RBCS lysis with releasing Hb in the form of hemosiderin, thus infarct caused by arterial occlusion become pale and depressed whereas in red infarct too much hemorrhage, congestion and edema so infarct area still red protruded and in with few days hemosiderin formed from lysis of RBCS to become red brown and protruded. 5. Infarction in brain may be pale or hemorrhagic, break of emboli give reopening of already closed artery that pour blood into infarct area (pale infarction) and become red due to this hemorrhage by reopened artery.
53. 53. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 53 Microscopically: 1. Area of ischemic coagulative necrosis except in brain may associated with liquefaction. 2. Inflammatory zone around rim of infarction within 1-2days. 3. Parenchymal regeneration begin at the periphery, all infarct area replaced by scar (fibrous tissue formation). 3-Septic infarction: when bacterial vegetation from heart cause emboli or microbe infect the infarct area or infarction occur in already infected area. Factors developing of infarcts: 1. Nature of blood supply 2. Rate of development of the occlusion 3. Vulnerability to hypoxia. 4. The oxygen content of blood. Clinical significance of infarction, 1. Myocardial and brain infarct are fatal 2. Pulmonary infarction are fatal 3. Bowel infarction are fatal 4. Ischemic necrosis of extremities (gangrene) in D.M. Shock: Is the peripheral circulatory deficiency due to decrease blood volume decrease cardiac output, increase blood concentration, lowering blood pressure and hyperkalemia. Categories of shock: 1. Cardiogenic shock this occur in cardiac failure in the following: a) Myocardial infarction b) Ventricular rupture c) Arrhythmia d) Cardiac tamponade e) Pulmonary embolism 2. Hypovolemic shock: hemorrhage, injury. fluid loss, vomiting, diarrhea. 3. Septic shock due to peripheral vasodilation and pooling of blood, endothelium Damage, disseminated intravascular coagulation in cases of; 1) Microbial infection, diffuse. Endotoxic shock. Septicemia. Fungal sepsis. 2) Super antigen toxic shock syndrome.
54. 54. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 54 4. Neurogenic shock: Loss of vascular tone and peripheral pooling of blood in the Anesthesia accidents. spinal cord injury. 5. Anaphylactic shock: systemic vasodilation and increase vascular permeability caused by IgE (type-1) hypersensitivity reaction (anaphylaxis), so vasodilation of B.V and pooling of blood in tissue result in tissue anoxia. Pathological changes in shock: 1. Congestion of viscera and edema in tissue of lungs are prominent findings. 2. Hyperemia and hemorrhage in gastrointestinal mucosa, adrenal gland and in any part of body. 3. Hyperemia and edema in the meninges are common. 4. Parcnethymatous degeneration in kidney, liver, myocardium and the adrenal gland. End Of Lecture 11
55. 55. All Rights Reserved 2017/Aliraqia University/Dentistry/Pathology /Prof.Dr. Khalil Hassan Zenad Aljeboori 55 Lecture 12 Prof.Dr.Khalil Hassan Zenad Aljeboori Immunopathology Body immune responses are normal defense mechanism designed to protect the body from various environments factors, but the diseases may result from: 1- Inadequate immune response.(immunodeficiency). 2- Inappropriate immune response.(autoimmune diseases ,Graft rejection). 3- Ex