Chapter 1 Introduction of Pathophysiology

Chapter 1 Introduction of Pathophysiology

Dr. Liu Rui (dr.liurui@Hotmail.com)Department of Physiology and Pathophysiology

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1. Nature and Aims of Pathophysiology Basic medicine Clinical medicine Practice Qualified doctor2 Pathophysiology is one of basic medicalsciences, which focus on sick or disorderedlife.

Basic medical courses normal body disordered body structure function structure function metabolism metabolism Anatomy Pathoanatomy Biology Physiology Pathophysiology Histology Biochemistry about drugs----Pharmacology Clinical medical courses

Internal medicine, Surgery, Pediatrics, et al.3

Pathophysiology is the study of the underlying mechanisms by which diseases occur and develop, and the study of the changes by diseases within the body. It provides a theoretical basis for the prevention, diagnosis and treatment.4

StructureIntact bodyFunctionMetabolism

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Alterationsin structureDiseaseAlterations in functionAlterations in metabolism

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Pathophysiology emphasizes the developmental process of diseases. Disruption of the bodys homeostasis; Alterations in function, metabolism

Mechanisms involved.7

2. Content of pathophysiologySystemic and organic pathophysiologyFundamental pathological processGeneral concept of diseasePathophysiology in diseases

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Experimental study Reproduce disease model in animals, isolated organs and cells, and observe or perform something. Clinical study Observe directly the patients symptom, laboratory testing, the rules of evolution; study the treatment and prognosis.Epidemiological study Study the cause or conditional factors, risk factors, rules of development of some infective diseases

93. Research Methods for Pathophysiology

Summary 1. Pathophysiology is one of basic medical sciences which study the rules of origin and evolution of diseases and the underlying mechanisms --- the physiology of disease.

2. Pathophysiology focuses on the alterations in function and metabolism of the body and the mechanisms underlying the development of diseases.

3. Pathophysiology plays an important role in bridge linking basic medical sciences to clinical medicine.10

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PathophysiologyPhysiologyDifferent targets

Normal body

Sick body11

PathophysiologyPathoanatomyDifferent Points

Function

MetabolismMechanismStructure12

PathophysiologyBridge courseBasic medicineClinical medicine13

Chapter 2 General Concepts of Diseases14

1. Basic Concepts1-1 HealthNo diseases or infirmity.A state of complete well-being of all aspects: physical, mental, social.151-2 DiseaseDisease is an abnormal life process caused by certain pathogenic factors, deviation from the normal status including structure, function or metabolism.

Disease is a disordered state of the body due to pathogenic agents-host interactions.16 Homeostasis: the process that the internal environment of an organism tends to remain balanced and stable, which is required for optimum functioning.Disease can be viewed as a disturbance of homeostasis.

Manifestations of diseases:17 1) Symptom: a subjective complaint 2) Sign: a manifestation that is noted by an observer, doctor or nurse, through physical examination, e.g. an elevated body temperature. 3) Laboratory finding: alterations found by laboratory test, X-ray examination (routine or CT), electrocardiogram (ECG), ultrasonography, magnetic resonance imaging (MRI), etc.

Sub-health There is a situation, in which the person does not show specific symptoms and signs of illness, but lives a low-quality of life both physically and mentally; this is called sub-health.

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Sub-health75%Health5%Disease20%

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Senescence (Aging)20 Aging is a natural, lifelong process. There is a general decline in the structure and function of the body with advancing age, resulting in a decreased reserve capacity of the various organ systems. This results in a reduction of homeostatic capabilities, making the older adult more vulnerable to stressors such as illness, surgery, medical administration, and environmental changes.

1-4 Two very important concepts 211) Pathological Process A series of structural, functional and metabolic changes that appear in different diseases, e.g. fever, inflammation, edema, etc.

Pathological Process and DiseaseDiseaseCauseSiteFundamental Pathological ProcessPneumoniaPneumococcusLungFever, inflammation, hypoxia, acid-base disturbances, shockDysenteryDysentery bacilliIntestineFever, inflammation, water and electrolytes disturbances, acid-base disturbances, shock Epidemic meningitisMeningococcusMeningesFever, inflammation, DIC, shock

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2) Syndrome A set of signs and symptoms that occur together and are characteristics of a group of diseases or a specific disease, e.g. ARDS, AIDSetc. 23

Acute respiratory distress syndrome (ARDS) Shock, infection

acute and severe lung damage

pulmonary edema

lung volumes and compliance, gas exchange impaired

tachypnea, labored breathing, cyanosis, chest radiograph shows diffuse, symmetrical interstitial and alveolar infiltration. 24

3. Etiology of Disease Etiology is a science to study the factorsassociated with or involved in initiation and development of diseases. According to their different roles in the development of diseases, these pathogenic factors are classified into cause of disease and conditional factors.25

Causes of diseases are the factors that provoke or cause the particular disease. It determines the characteristics of the disease and is absolutely necessary for disease to occur. 26 Conditional factors are the factors that do not cause disease directly but rather influence the pathogenesis and the natural time course of the disease.

Precipitating factors belong to conditional factors that promote the development of diseases by enhancing the roles of cause of diseases or susceptibility of the body to diseases.27

e.g. Infection, arrhythmias, pregnancy, water-electrolytes and acid-base disturbances areprecipitating factors of heart failure Tubercle bacillus is the cause of tuberculosis. Not all people who inhale the organism willsuffer from pulmonary tuberculosis, whichoccurs in malnutrition, over fatigue and long-term depress.28

Controlling conditional factors is easier thaneliminating the causes. 29

Causes of diseases Extrinsic Factors Biological agents Physical factors Chemical factors Nutritional factors Pathogenic factors Intrinsic Factors Genetic factors Congenital factors Immunological factors Psychological factors Conditional factors Body condition (predisposing factors) Nature condition Social condition

Precipitating factors of diseases

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3-2 Cause of Disease1) Biological agents bacteria, viruses,

2) Physical factors: trauma and fracture, heatstroke, frostbite.

3) Chemical factors Corrosive chemicals such as strong acid and bases can destroy cells at the site of contact. Cell-injurious chemicals are often called toxic substances or poison. They induce tissue and cell damage when they enter the body through certain pathways and reach a sufficient amount. These called intoxication or poisoning. The toxic substances often act on specific cells or organs, e.g. CO poisoning.Electrical injuriesRadiation injuries31

4) Nutritional factorsExcesses: high lipids and carbohydratesdiet obesity, atherosclerosis, diabetesDeficiencies: lack of certain elements in diet(1) Vitamin B: beriberi(2) Vitamin A: night blindness(3) Vitamin C: scurvy(4) Vitamin D: rickets

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3-2-2 Intrinsic Factors 1) Genetic factors Altered genetic material passed from parent to offspring is called genetic factors, which is classified into three groups.

Genetic disorders Chromosome disorders: the defect results from numerical and structural abnormalities of chromosome. Single-gene disorders: the defect is caused by a single defective or mutant gene. Multifactorial inheritance: polygenetic disorder.

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Common Examples of Genetic Disorders34DisorderClassificationGenetics Huntington diseaseSingle-gene disorderAutosomal dominantCystic fibrosisSingle-gene disorderAutosomal dominantHypophosphatemia (vitamin D-resistant rickets)Single-gene disorderX-lined dominantHemophiliaSingle-gene disorderX-lined dominantDown syndromeChromosome disorderTrisomy 21Turner syndromeChromosome disorder45, X

Turner syndrome3545, X

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Down syndrome

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Inherited disease: disease caused by alteredgenetic material, either single gene mutation orchromosome aberrations. e.g. color blindness,Albinism, Down syndrome. 37

38Disorder of multifactorial inheritanceresult from a combination of the multiple genevariations with environmental factors. Thereforethe disease on phenotype are not hereditary, butthese diseases do have a genetic background (genetic susceptibility), such as congenital heart disease, cleft lip, coronary artery disease andhypertension.

Genetic predisposition (genetic susceptibility):a state of body favorable to or showing atendency to certain diseases because ofpolygenetic abnormalities.39

2) Congenital factors Environment factors that occurred duringembryonic or fetal development are calledcongenital factors, including the physiologicstatus of the mother (maternal disease) andteratogenic agents (infections or drugs takenduring pregnancy), which acts on the embryo orfetus, causing abnormalities in form or function.Diseases caused by congenital factorscalled congenital disease. e.g. congenital syphilis.40

3) Immunological factors Although the immune response is a normalprotective mechanism, it may cause disease whilethe response is deficient (immunodeficiencydisease), inappropriately strong (allergy orhypersensitivity----penicillin), or misdirected(autoimmune disease----ankylosing spondylitis).41

4) Psychological factors Anxiety, strong or persistant psychologicalstimulation or stress may lead to mental illnessand may be related to some disease such ashypertension, peptic ulcer(duodenal ulcer), and coronary heart disease.

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3-3 Conditional Factors 1) Bodys condition: age, sex, race; physical training, mental condition, fatigue, smoking, lifestyle. 2) Nature condition: weather condition and geographical environment influence some epidemical diseases. 3) Social condition: labor and hygiene conditions----occupational diseases, social life events----persons mood and life pattern.43

CauseConditional factors

BodyDisease

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Causes of diseases Extrinsic Factors Biological agents Physical factors Chemical factors Nutritional factors Pathogenic factors Intrinsic Factors Genetic factors Congenital factors Immunological factors Psychological factors Conditional factors Body condition (predisposing factors) Nature condition Social condition

Precipitating factors of diseases

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4. Pathogenesis of disease Pathogenesis of disease refers to the rules andmechanisms underlying the development or evolution of the diseases.4-1 General rules for pathogenesis of disease 1) Disruption of homeostasis If homeostasis is disrupted by a variety ofharmful agents, the body cannot functionoptimally, and illness may occur.46

2) Process of damage and anti-damage Damage can induce bodys anti-damage responses. The development of a disease depends on the strength of damage and anti-damage factors. Too much anti-damage process will cause new injury to the body (SIRS----MODS)47

3) Reversal role of cause and result The cause of the disease lead to a result, which can be another cause of the disease in the evolution process. (Cause) (Result) Chronic hypoxia erythrocyte polycythemia (Cause) (Result) blood viscosity thrombus

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Mechanical trauma HemorrhageCardiac outputReturned blood volume Blood pressureMicrocirculation congestionSympathetic nerve exciteCapillary openVasoconstrictionHypoxia in tissure

vicious cycleMaintain BPHeart rate Contractility

beneficial cycleRecovery

(Cause)(Result)(Cause)(Result)49

4) Correlation between systemic and localregulations Local alterations can affect the whole body through neural and humoral regulation, and the systemic functional statues can in turn affect the development of local damages via the same regulating strategies.50

e.g. a severe furuncle congestion and edema (local) fever, chill and WBC (systemic)

e.g. a recurrent furuncle may represent systemic metabolic disorder caused by diabetes. 51

5. Outcome of Diseases52RecoveryDeath

Complete recoveryIncomplete recovery

5-1 Complete recoveryThe alterations of the function, metabolism and structure of the body, which appeared in disease, are perfectly restored.The signs and symptoms of the disease are disappear entirely. 53

5-2 Incomplete recoveryThe main symptoms are absent.Some pathological changes are still present in the body.It is brought about by the compensatory response to maintain a relatively normal life activity. --e.g. Heart disease patients54

5-3 Death5-3-1 Definition: Irreversible cessation of the function of the body as a whole.

Contemporary concept of death is brain death.55

5-3-3 Definition of brain death Prolonged irreversible cessation of all brain functions, including the brain stem.5-3-4 Diagnosis of Death The bases for demonstrating brain deathare the absence of brain stem reflexes, absenceof cortical activity and demonstration ofirreversibility of the state. 56

Criteria indicating brain death Irreversible coma and cerebralunresponsiveness: complete lack of cerebralresponse to any form of external excitation. Absence of all brain stem reflexes: It includes the absences of pupilary reflex, corneal reflex, cough reflex and swallowing reflex. Cessation of spontaneous respiration57

Absence of any electrical activity of brain indicated by EEG (electroencephalogram) for at least 6 hours. Cessation of cerebral circulation58

Brain death versus vegetative stateItemBrain deathVegetative stateDefinitionCessation of all brain functionsCessation of recognizing ability of brainSpontaneous respirationNoYesConsciousnessCessationSleep-awakening cycle without consciousnessBrain stem reflexes NoYesReversibilityNoYes

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Summary 1. Disease is an abnormal life process in whichthe bodys homeostasis is disrupted by theinteractions of certain pathogenic factor andthe body. Intrinsic changes of diseases arealterations in structures, functions andmetabolisms of the body. 2. A set of structural, functional and metabolicchanges that occur together in different diseaseis called pathologic process.60

3. Pathologic factors include cause of diseasethat provoke disease and determine itscharacteristics and conditional factors thatparticipate in and influence the pathogenesis ofdisease. Conditional factors that promote thepathogenesis of disease are called precipitatingfactors.61

4. Irreversible cessation of all brain functions,including the brain stem is called brain death.The bases for determine it are absence ofcortical activity, absence of brain stem reflexes,and demonstration of irreversibility of the state.

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