Crash Course in
Crash Course in
Pathophysiology Questions & Answers
Pathophysiology
Questions & Answers
Ataman O.
Crash Course in Pathophysiology
Questions & Answers
Vinnytsia Nova Knyha 2019
УДК 1(075) А95
Автор: Олександр Васильович Атаман – доктор медичних наук, професор, завідувач кафедри фізіології і патофізіології з курсом медичної біології Сумського державного університету МОН України. Рецензенти: І. В. Савицький, професор кафедри загальної та клінічної патологічної фізіології ім. В. В. Підвисоцького Одеського національного медичного університету, доктор медичних наук, професор. М. С. Регеда, завідувач кафедри патологічної фізіології Львівського національного медичного університету ім. Данила Галицького, доктор медичних наук, професор. М. О. Клименко, професор кафедри медичної біології, хімії, біохімії, мікробіології, фізіології, патофізіології і фармакології Чорноморського національного університету ім. Петра Могили (м. Миколаїв), доктор медичних наук, професор. В. О. Костенко, завідувач кафедри патофізіології ВДНЗУ “Українська медична стоматологічна академія”, доктор медичних наук, професор.
А95
Атаман О. В. Crash Course in Pathophysiology. Questions & Answers = Короткий курс патофізіології. Запитання та відповіді : посібник англ. мовою / О. В. Атаман. – Вінниця : Нова Книга, 2019. – 520 с. ISBN 978-966-382-798-8 У посібнику у формі запитань і відповідей викладено основні розділи патологічної фізіології згідно з навчальною програмою для студентів вищих медичних навчальних закладів. Для студентів вищих медичних навчальних закладів. Може бути корисним для лікарів усіх спеціальностей під час підготовки до іспитів на кваліфікаційну категорію. УДК 1(075)
ISBN 978-966-382-798-8
© Атаман О. А., 2019 © Нова Книга, 2019
CONTENT
MODULE I GENERAL PATHOPHYSIOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Content module 1. General doctrine of disease, etiology and pathogenesis. Pathogenic effects of environmental factors. Role of internal factors in pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Lesson 1. Subject, tasks and methods of pathophysiology . . . . . . . . . . . . . . . . . . . . .6 Lesson 2. General nosology, etiology and pathogenesis. . . . . . . . . . . . . . . . . . . . . . 11 Lesson 3. Pathogenic effects of environmental factors . . . . . . . . . . . . . . . . . . . . . . 23 Lesson 4. The role of heredity, constitution and age factors in pathology. Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Lesson 5. Reactivity and resistance. Pathophysiology of immunological reactivity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Lesson 6. Allergy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Content module 2. Typical pathological processes . . . . . . . . . . . . . . . . . . . . . . . 78 Lesson 7. Cell Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Lesson 8. Peripheral circulatory disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Lesson 9. Inflammation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 Lesson 10. Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Lesson 11. Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Content module 3. Typical metabolic disorders. . . . . . . . . . . . . . . . . . . . . . . . . 160 Lesson 12. Impairment of energy metabolism. Starvation . . . . . . . . . . . . . . . . . . 160 Lesson 13. Impairment of carbohydrate metabolism. Diabetes . . . . . . . . . . . . . . 169 Lesson 14. Impairment of fat and protein metabolism . . . . . . . . . . . . . . . . . . . . . . 189 Lesson 15. Impairment of water-salt metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . 200 Lesson 16. Impairment of calcium and phosphate metabolism . . . . . . . . . . . . . . 215 Lesson 17. Impairment of the acid-base homeostasis . . . . . . . . . . . . . . . . . . . . . . 223
Content module 4. Pathophysiology of the blood system. . . . . . . . . . . . . . . . . 233 Lesson 18. Disorders of the red blood cell system. Posthemorrhagic anemia. . . 233 Lesson 19. Hemolytic anemia and anemia due to hematopoietic disorders . . . 246 Lesson 20. Leukocytosis and leukopenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
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MODULE ІІ PATHOPHYSIOLOGY OF THE ORGANS AND SYSTEMS . . . . . . . . . 232
Lesson 21. Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 Lesson 22. Hemostasis disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 Content module 5. Pathophysiology of systemic circulation and external respiration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 Lesson 23. Heart failure. Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301 Lesson 24. Insufficiency of the coronary circulation. Cardiac ischemia . . . . . . . 325 Lesson 25. Pathophysiology of blood vessels. Atherosclerosis. Hypertension . . . 336 Lesson 26. Pathophysiology of external respiration . . . . . . . . . . . . . . . . . . . . . . . . 355 Lesson 27. Hypoxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372 Content module 6. Pathophysiology of digestion, liver and kidneys . . . . . . . . 382 Lesson 28. Digestive disorders in the oral cavity and stomach. Peptic ulcer . . . 382 Lesson 29. Digestive disorders in the intestines. Acute pancreatitis. Intestinal obstruction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406 Lesson 30. Pathophysiology of liver. Hepatic insufficiency . . . . . . . . . . . . . . . . . . 415 Lesson 31. Pathophysiology of kidneys. Renal insufficiency . . . . . . . . . . . . . . . . . 433
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Content module 7. Pathophysiology of regulatory systems and extreme conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 Lesson 32. General pathophysiology of the endocrine system. Adenohypophysis and neurohypophysis disorders . . . . . . . . . . . . . . . . . . . . . . . . 453 Lesson 33. Pathophysiology of peripheral endocrine glands. . . . . . . . . . . . . . . . . 467 Lesson 34. Pathophysiology of the nervous system . . . . . . . . . . . . . . . . . . . . . . . . 491 Lesson 35. Pathophysiology of extreme conditions. Shock. Coma . . . . . . . . . . . 514
MODULE I
GeNeraL PaThoPhYsIoLoGY
ConTEnT moDulE 1. General doctrine of disease, etiology and pathogenesis. Pathogenic effects of environmental factors. Role of internal factors in pathology
Lesson 1. Subject, tasks and methods of pathophysiology 1.1. What is pathophysiology? What does it study? Pathophysiology is a science that studies general laws of occurrence, development and completion of disease. It is a science that studies the vital functions of a sick human body. 1.2. What is the peculiarity of pathophysiology subject? Disease and diseased organism are subjects of study of many general theore tical medical and all clinical disciplines. Peculiarity of pathophysiology subject is that it studies the general in disease, i.e., the most general patterns of occurrence and development of disease, while other sciences study particular, special and specific. 1.3. What are the scientific tasks of pathophysiology?
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1. Establishing the essence of disease (what is a “disease”?). 2. Studying the causes and conditions of disease occurrence. 3. Disclosure of the disease development mechanisms and its particular ma nifestations, establishment of disease course patterns and the mechanisms of convalescence. 4. Determining the general principles of disease prevention and treatment. These tasks find their solution within four components of pathophysiology as a science: nosology, etiology, pathogenesis, experimental therapy.
1.4. how is pathophysiology connected to other sciences? The following connections can be distinguished (Fig. 1): 1. Сonnection with the sciences that study the properties of environmental factors that can cause diseases (physics, chemistry, biology, microbiology, sociology). These sciences provide information necessary for the study of etiology. 2. Сonnection with the sciences that study the properties of organism and its functioning (cytology, embryology, histology, normal physiology, biochemistry, immunology, genetics). These sciences form the basis for the study of pathogenesis. 3. Сonnection with general theoretical sciences that study disease (pathological anatomy, pharmacology). These sciences together with pathophysiology create a holistic picture of the disease. 4. Сonnection with clinical sciences. Pathophysiology determines the main etiological and pathogenetic principles of prevention, diagnosis and treatment of the disease.
Clinical practice Pathological anatomy
Pathophysiology
Physics
Disease
Pharmacology Histology
Chemistry
Normal physiology
Microbiology
Biochemistry
Biology
Immunology
Sociology
Genetics
Environment
Organism
Fig. 1. Relationship of pathophysiology with other sciences
1.5. What is the connection between pathophysiology and clinical practice? The clinical practice sets problems for pathophysiologists and provides the actual material necessary for their solution. Pathophysiology, being scientific basis of medicine (the philosophy of medicine), establishes etiology and pathogenesis of diseases and on this basis determines the main directions of their prevention and treatment (Fig. 2). 1.6. What methods does medicine use in the study of diseases?
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Disease is studied using four main methods: clinical, epidemiological, anatomical and experimental.
Etiological factors
Physical
Chemical
Biological
Social
Hereditary
Etiology
ORGANISM Disorders
Structural
Functional
Immune
Metabolic
Pathogenesis
DISEASE Prevention
Diagnostics
Treatment
Clinical practice
Fig. 2. Pathophysiology – general theoretical basis of medicine
Clinical method is a study of the disease directly at the bedside of a sick person. Pathophysiology has always used this method to solve the tasks assigned to it. modern achievements of science make it possible to study a large number of functional, biochemical, immunological and other indicators in a sick person. In connection with this, one of the directions of pathophysiology is developing rather quickly today – clinical pathophysiology. Epidemiological method uses the population of people as an object of studying the disease. It is of the utmost importance for establishing the causes and patterns of infectious diseases. Pathophysiology does not apply this method directly, but uses obtained data, associated with etiology of major noninfectious diseases (e.g., risk factors of atherosclerosis). Anatomical method is the main method of pathological anatomy, which, together with pathophysiology, studies the essence of disease, using the corpse of a person or tissue obtained from the patient as an object. Experimental method involves studying the disease in laboratory animals that are the object of modeling human diseases. 1.7. What is the main method of pathophysiology? What is its peculiarity? The main method of pathophysiology is experiment. In the broad sense of the word “experiment” is an active influence on nature by man and artificial reproduction of its various phenomena with the aim of understanding objective patterns. The peculiarity of pathophysiological experiment consists in reproduction of experimental models of diseases on experimental animals in order to establish the mechanisms of their origin, development and outcome in humans.
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1.8. What is experimental model of disease? Experimental model of disease is artificial reproduction of disease on laboratory animals, which has certain features of corresponding human disease.
1.9. What is the significance of pathophysiological experiment as a method of studying the disease in humans? 1. Although experiment on animals does not reproduce full picture of relevant disease in humans, it provides an opportunity to observe and study the disease from the onset to its end. It is impossible in the clinical practice. 2. In experiment it is possible to control environmental conditions affecting the course of disease, as well as initial state of the animals that are the subject of experiment. 3. Experiment is the only way to study such influences on body, the use of which in clinical practice is unacceptable (trauma, transplantation of tumors, irradiation). 4. Experimental research provides an objective material for presenting of scientific theories. 1.10. What are the types of experiments? There are acute and chronic experiments. Acute experiment (vivisection) is based on surgical intervention in the animal’s organism. It allows to study acute disorders in organism, e.g., shock collapse, crush syndrome, acute insufficiency of respiration, blood circulation, kidneys, etc. Chronic experiment is a long one, when it is possible to study the dynamics of disease. It is used to model chronic diseases, for example, atherosclerosis, hypertension, diabetes, peptic ulcer, etc. 1.11. What are the stages of pathophysiological experiment? 1. Planning an experiment. 2. modeling of pathological process. 3. obtaining information about the changes in body of experimental animals. 4. Analysis and synthesis of obtained results. 1.12. What is an experiment planning? This stage of experimental research includes: а) creation of working hypothesis; b) setting goal and objectives of the study; c) determining the object of experiment (species, age, sex of animals); d) choosing the design of experiment (the nature and frequency of pathogenic influences, dose, duration, etc.); e) determining the scope of research (number of experiments, a list of specific techniques to be used).
Method of removal. Removal of the liver is used to model hepatic insufficiency, kidneys removal causes acute renal failure, removal of pancreas results in diabetes, when pituitary gland is removed panhypopituitarism develops.
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1.13. What are the methods of disease modeling?
Method of destruction (damage). For this purpose, surgical interventions (nerve cutting, destruction of nerve centers, tissue damage), physical factors (ionizing radiation, temperature, etc.), chemical agents (poisons, inhibitors), immune effects (antitissue sera, antibodies) are used. Method of overload. By causing functional overloads of higher centers of central nervous system, you can simulate neuroses; by creating artificial heart defects, you can reproduce heart failure; introduction of large amounts of cholesterol and naCl models atherosclerosis and hypertension respectively. Method of creating a deficit. By creating oxygen deficit in the pressure chamber, you can simulate hypoxia; by excluding vitamins from diet, you can get avitaminosis and hypovitaminosis, antioxidant insufficiency. Method of violation of nervous and hormonal regulation. Irritation or damage to nerve structures, pharmacological interventions in the exchange of neurotransmitters, administration of large amounts of hormones or their analogues are widely used. Method of creating barriers. By ligating the blood vessels, you can simulate myocardial infarction and hypertension, and by ligating common bile duct – mechanical jaundice. myocardial infarction is reproduced by insertion of emboli into coronary vessels. Method of exogenous induction. You can introduce in the body or act on it by factors that are specific pathogens of the disease. That is how all infectious diseases, malignant tumors, allergies are modeled. Method of transplantation is used in the study of malignant tumors, sclerotic vascular diseases. Explantation method is the study of pathological processes outside the body: in tissue cultures, on isolated organs. This method is used in the study of tumor growth, atherosclerosis, allergic reactions. 1.14. What methods does pathophysiology use to obtain information about changes in the body of experimental animals? 1. Morphological (macroscopic study, light and electron microscopy, etc). 2. Functional (registration of muscle contractions, electrocardiography, encephalography, recording of spirograms, determination of oxygen consumption, etc). 3. Biochemical (determination of substrate concentration, hormones, electrolytes, metabolic products, enzyme activity). 4. Immunological (definition of antibody titer, blasttransformation of lymphocytes, etc.). using these methods, information on changes at the molecular, subcellular, cellular, tissue, organ, systemic levels and at the level of the organism as a whole is obtained.
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1.15. What methods of results analysis can be used in experimental studies? 1. Mathematical methods. These include statistical methods to identify the correlation between different groups of indicators; methods of mathematical modeling.
mechanisms of the aging
mechanisms of the vitauktum
Damage to DNA
DNA repair systems
Free radicals and peroxides
Antioxidant systems
Toxic products
Mechanisms of detoxification
Damage to cells
Reparative synthesis of cellular structures, etc. (see lesson 7)
Cell death
Compensatory hyperfunction and hypertrophy of the remaining cells
Hypoxia
Antihypoxic mechanisms
Stress
Mechanisms of stress limitation
It is believed that each mechanism of aging corresponds to a certain mechanism of vitauktum. 4.41. What is progeria? Progeria is a pathological aging that occurs as a result of action of pathogenic factors on the body. An example is the Hutchinson – Gilford syndrome. This is an autosomal recessive hereditary disease. Its first signs appear very early, already in the first year of life. It is characterized by growth retardation, graying hair, baldness. Skin aquires features of an old skin, cataracts and atherosclerosis develop. Death, as a rule, occurs in 1–2 decade of life. 4.42. What is geroprotection? What approaches does it use? Geroprotection is a direction in medicine that studies ways of increasing life expectancy, slowing down the rate of aging, delaying the onset of pathology associated with the age of a person. It is believed that the factors of prolonging life are diet, motor activity, antioxidants. The geroprotective action of physiologically active substances (polyvitaminic complexes, gerovital, aspirin, latirogens, microelements) and enterosorbents is studied.
Lesson 5. Reactivity and resistance. Pathophysiology of immunological reactivity Reactivity is a property of an organism and its structures to respond to the environmental factors by changes in its vital activity.
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5.1. What is reactivity?
Reactivity ensures interaction of the organism with the surrounding world. It significantly affects the development and course of diseases. 5.2. Give examples of reactivity manifestations at different levels of living objects` organization. At the molecular level – shift in the dissociation curve of oxyhemoglobin to the right in conditions of acidosis caused by hypoxia (Bohr effect). At the cellular level – implementation of phagocytosis by leukocytes in response to tissue invasion by microorganisms. At the tissue level – development of a complex of reactions called “inflammation” in response to the action of damaging factors (see lesson 9). At the organ level – increase in heart rate with increasing blood temperature. At the systemic level – reactions of the systems of external respiration, blood circulation and blood during oxygen starvation (see lesson 27). At the level of the organism as a whole – complex orienting reactions in response to the sound and light signals. 5.3. What types of reactivity are distinguished? The following reactivity types are distinguished: a) species, group and individual. Species reactivity is inherent in all individuals of a given species; group reactivity is specific to a certain group of individuals, individual – to a specific individual; b) nonspecific and specific. Nonspecific (primary, simple) reactivity manifests itself under the influence of various factors on the body. It is based on genetically programmed standard response variants (e.g., protectivecompensatory reactions under the action of high and low temperatures, during oxygen starvation, phagocytosis, etc.). Immunological reactivity is termed specific. (see below); c) physiological and pathological. Physiological reactivity includes the reactions of a healthy organism. Qualitatively changed reactivity under the action of pathogenic factors on the body is termed pathological reactivity. Its example is an allergy (see lesson 6); d) increased (hyperpergia), decreased (hypoergia) and perverted (dysergia). Great value in the development of the theory of different types of reactivity belongs to the works of n. Sirotinin and his disciples.
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5.4. What factors influence reactivity of the human body? 1. Age. Early childhood is characterized by low reactivity. Reactivity gradually increases, reaches its maximum in adults, and at an old age it starts to decline. 2. Sex. 3. Heredity. 4. Constitution.
5. Functional state of the nervous, endocrine, immune systems and connective tissue. 6. Factors of the environment (climate, nutritional habits, social conditions, etc.). 5.5. What is resistance? Resistance is a body’s ability to resist to the action of pathogenic factors. 5.6. What types of resistance are distinguished? Resistance can be passive and active, nonspecific and specific. The basis of specific resistance is immunological reactivity. 5.7. What is passive and active resistance? How do they differ from each other? Passive resistance is insensitivity to the action of the pathogenic factor, in susceptibility to it. It occurs when interaction of the organism with the pathogenic factor is impossible or difficult. Passive resistance is not dependent on energy supply and can be due to the following mechanisms: 1. Existence of barriers for interaction of the pathogenic factor with the structures of organism (biological barriers); 2. Absence or destruction of body structures capable of interacting with pathogenic factor, e.g., the absence of receptors for pathogenic viruses; 3. Destruction of the pathogenic factor by mechanisms not associated with the body’s response to the action of this factor (e.g., destruction of cholera vibrio by gastric juice); 4. Slowing down of the pathogenetic mechanisms, triggered by interaction of the organism with pathogenic factor (e.g., an increase in passive resistance in case of hypothermia). Active resistance is stability, which is provided by a complex of protectivecompensatory reactions aimed at destroying the pathogenic factor and the consequences of its action. Active resistance energy dependent, its basis is the mechanisms of reactivity (e.g., phagocytosis, antibody synthesis, cellular immunity response).
These include: (1) cell areactivity, (2) physical and physicochemical factors, (3) biological barriers, (4) antagonistic relationships between normal and pathogenic microflora, (5) functioning of the physiological system of connective tissue, (6) humoral factors of nonspecific resistance, (7) phagocytosis, (8) inflammation.
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5.8. Name the mechanisms of nonspecific resistance which ensure organism’s resistance to the action of infectious agents.
5.9. What is areactivity of cells as a mechanism of nonspecific resistance to infections? Areactivity of cells is their inability to interact with an infectious agent. It can be caused by: (a) absence of receptors for viruses on the cell surface; (b) absence of receptors for bacterial toxins in cells; (c) toxin binding to receptors of cells that are not sensitive to its action (receptor screening). 5.10. What physical and physico-chemical factors are factors of nonspecific resistance to infections? 1. Temperature. In birds, the temperature level ensures their insensitivity to the pathogen of anthrax. When the body temperature rises, reproduction of many viruses is disrupted and they die. 2. pH value of the medium. In acidic content of the stomach, many pathogens of infectious diseases die, in particular, the cholera vibrio. In the focus of inflammation, high concentration of hydrogen ions is created, which causes damage to the microorganisms present. 3. Partial pressure of oxygen in tissues. under normal conditions, po2 in tissues is enough to prevent the development of anaerobic infections. 5.11. how to classify the biological barriers of the body? Biological barriers are divided into external and internal. External barriers are skin and mucous membranes. Among the internal there are some organ barriers (liver) and histohematic barriers. The latter divide blood and tissues. Histo-hematic barriers are divided into nonspecialized and specialized. Non-specialized barrier is the capillary wall and consists of the endothelium and the basal membrane. The structure of specialized barriers includes additional structures that significantly affect their permeability. Specialized barriers are bloodbrain, bloodocular, bloodtesticular, bloodthyroid and bloodcochlear barriers.
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5.12. What functions are performed by the physiological system of connective tissue? A. A. Bogomolets was the first to point out the important role of connective tissue in organism’s resistance. He was the one to introduce the term “physiological system of connective tissue”. This system performs the following functions: 1. Protective (creation of biological barriers, phagocytosis, humoral and cellular immunity responses); 2. Trophic (providing nutrition to parenchyma elements); 3. Supportive, plastic.
5.13. What is Bogomolets` serum? What is serum’s mechanism of operation? Bogomolets` serum is called antireticular cytotoxic serum (ACS), first obtained and proposed in medical practice by A. A. Bogomolets. This serum contains antibodies against connective tissue components. When small amount of serum is administered, the healing processes of wounds and ulcers are accelerated, and slow inflammatory processes are resolved. The mechanisms of action of ACS are associated with the development of cytotoxic immune responses (see lesson 6). 5.14. Give examples of humoral factors of nonspecific resistance to the action of infectious agents. These factors include lysozyme, Creactive protein, inhibitors of bacterial enzymes, interferons, complement system. 5.15. What are interferons? Interferons are lowmolecular proteins that are formed in virusinfected cells and protect other cells from damage by viruses. under the action of interferons in an uninfected cell, the formation of proteininhibitors is stimulated, which inhibit the synthesis of viral nucleic acids and thus violate reproduction of viruses. Interferons protect cells not only from the type of viruses which infected an organism, but also from others.
Complement is a system of serum proteins, sequential activation of which causes damage (perforation) of cell membranes and, as a result, the destruction (lysis) of bacteria. Complement system consists of 11 proteins, which make up 9 fractions, denoted C1, C2, ..., C9. Complement proteins are regulated by the same number of inhibitors and inactivators. There are several mechanisms of complement activation. 1. Classical pathway (antibodydependent). Activation of complement is associated with the formation of antigenantibody complexes on the surface of the bacterial cell. 2. Alternative pathway. Activation of complement is directly caused by poly and liposaccharides of the bacterial wall. This mechanism requires the participation of serum proteins, called properdin. 3. Nonspecific activation. It can be carried out by active proteases (trypsin, plasmin, kallikrein, lysosomal enzymes, etc.) at any stage of the activation process.
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5.16. What is the complement system? How is it activated?