Dr. Xiyun Dr. Xiyun DengDeng ( ( 邓锡云邓锡云 ))

Dept. of PathologyDept. of Pathology

Medical CollegeMedical College

Hunan Normal UniversityHunan Normal University

(( 湖南师范大学医学院病理学教研室湖南师范大学医学院病理学教研室 )) 1

PathophysiologyPathophysiology（病理生理学）（病理生理学）

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Overview of Overview of PathophysiologyPathophysiology

Concept of PathophysiologyConcept of Pathophysiology

Brief history of PathophysiologyBrief history of Pathophysiology

Methods of Pathophysiology researchMethods of Pathophysiology research

Pathophysiology ≠ Pathology + Physiology

Pathophysiology

Pathophysiology

Pathophysiology

Physiology

Physiology

Disease

Normal PathologyPathology

Function & Metabolis

m

Morphology

(Structure)

Pathophysiology

Pathophysiology

Definition: The discipline that describes the changes of the function and metabolism of the disease and the mechanisms involved.

Task: To reveal the nature of the disease and provide a theoretical basis for the prevention and treatment of disease.

Pathophysiology

Pathophysiology

PhysiologyPhysiology

Different Subjects

Normal Subjects Diseased Subjects

PathologyPathology

Different Viewpoints

Function & Metabolism

Morphology

Is a bridge between basic medical sciences and clinical medical sciences.

Guidance for clinical practices.

Why Is Pathophysiology Important?

Basic Medical

Sciences

ClinicalMedical Sciences

Pathophysiology

Histology & Embryology

AnatomyPhysiology

BiochemistryPathology

…

Internal MedicineSurgeryPediatricsOB/GYNInfection Diseases…

Brief History of Pathophysiology

Morgagni (1692~1771): Organ Pathology(Italian anatomist)

Virchow (1821~1902): Cell Pathology(German pathologist)

Bernard (1813~1878): Experimental Pathology(French physiologist)

Kazan University (1879-): Pathophysiology(Russian)

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Methods of Pathophysiology Methods of Pathophysiology ResearchResearch

Experimental researchExperimental research

Animal modelsAnimal models

Cell biology experimentsCell biology experiments

Molecular biology experimentsMolecular biology experiments

Epidemiological researchEpidemiological research

Clinical researchClinical research

Dept. of PathologyDept. of Pathology

Medical CollegeMedical College

Hunan Normal UniversityHunan Normal University

(( 湖南师范大学医学院病理学教研室湖南师范大学医学院病理学教研室 ))8

Chapter 1Chapter 1

Conspectus of Conspectus of DiseaseDisease

（疾病概论）（疾病概论）

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Conspectus of DiseaseConspectus of Disease

Concept of health and diseaseConcept of health and disease

Etiology of diseaseEtiology of disease

Pathogenesis of diseasePathogenesis of disease

Outcome of diseaseOutcome of disease

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Health (Classic Concept)Health (Classic Concept)

The state of the organism when it functions optimally without evidence of disease.

Health (WHO definition)Health (WHO definition)

Health indicates not only without any evidence of disease, but also a state of complete well-being physically, psychologically and socially.

Concept of Disease (Dis + ease)

An abnormal life process involving physical, mental and social problems which is induced by imbalance of homeostasis under the action of certain causes.

Diseases are manifested by a series of symptoms and signs.

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Symptom ( 症状 )

An abnormal feeling noticed by a patient.(headache, stomachache, fever, cough…)

Sign ( 体征 )

An objective indication of some medical fact or characteristic that may be detected by a physician.(body temperature, respiration, pulse, blood pressure…)

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Sub-Health (亚健康）(Sub-optimal Health Status, SHS)

A situation in which the person does not show A situation in which the person does not show specific symptoms or signs, but lives a low-quality of specific symptoms or signs, but lives a low-quality of life both physically and mentally. life both physically and mentally.

ManifestationsManifestations

PhysicallyPhysically Tiredness, low-spiritedTiredness, low-spirited

Psychologically Psychologically Irritable, stressfulIrritable, stressful

SociallySocially Bad human relations, lonely Bad human relations, lonely

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Sub-healthSub-health

HealthHealth DiseaseDisease

Relationship AmongRelationship AmongDifferent Health/Disease StatesDifferent Health/Disease States

Health

Disease

Sub-health

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Conspectus of DiseaseConspectus of Disease

Concept of health and diseaseConcept of health and disease

Etiology of diseaseEtiology of disease

Pathogenesis of diseasePathogenesis of disease

Outcome of diseaseOutcome of disease

2. Etiology

( 病因学 )The study of the many factors (causes and conditions) coming together to cause a disease. 

Classifications:Causative factorsConditions

•Predisposing factors •Risk factors

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2.1 Causative Factors (原因 )

Extrinsic causesBiological

Chemical

Physical

Nutritional

Intrinsic causesGenetic

Congenital

Immunological

Psychological

A cause of a disease is an event that precedes the disease in a disease cause chain. Without this event, the disease either would not have occurred at all or would occur at a later time. 

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1) Biological AgentsMicroorganisms and parasites ( 病原微生物和寄生虫 )

Bacteria

Viruses

Fungi

Rickettsia

Spirochete

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2) Chemical AgentsCorrosive chemicals

Strong acids or alkalis

Carbon monoxide

Formaldehyde

Nitrosamine

Polycyclic Aromatic Hydrocarbons, PAHs

……

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45,612 in China (2013)878 carcinogenic

3) Physical Agents

Mechanical forces Trauma

Extremes of temperature Burn/Freezing

Electric shock Shock

Radiation Irradiation damage

(X-ray, Gamma, UV, Microwave)

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Nutritional imbalancesNutritional imbalances

Nutritional deficiencyNutritional deficiency Nutritional excessNutritional excess

4) Nutritional Imbalances

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Vitamin deficiency (avitaminosis)

Vitamin A  night blindness ( 夜盲症）Vitamin B1 beriberi ( 脚气病 )

Vitamin B3 pellagra ( 糙皮病 )

Vitamin C scurvy ( 坏血病 )

Vitamin D rickets ( 佝偻病 )

Vitamin K impaired coagulation ( 凝血病 )

Iron deficiency anemia ( 贫血 )

High lipids & carbohydrates obesity, atherosclerosis, diabetes

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2.1 Causative FactorsExtrinsic causes

Biological

Chemical

Physical

Nutritional

Intrinsic causesGenetic

Congenital

Immunological

Psychological 26

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Genetic factors

*Alterations in genetic materials Gene mutation Chromosomal aberration

Hereditary factors

Genetic Factors

Hemoglobin gene mutation Sickle-cell anemia

Factor VIII deficiency Hemophilia

Photopigments genes missing or damagedColor blindness

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Congenital FactorsCongenital Factors

Congenital heart defectCongenital heart defect

Congenital limb defectCongenital limb defect

A congenital disorder, or congenital disease, is a A congenital disorder, or congenital disease, is a condition existing at condition existing at birth or during the first month  or during the first month of life (of life (neonatal disease).  disease).

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Congenital factorsCongenital factors

*Harmful agents acting on fetus*Harmful agents acting on fetus

Cleft lip(( 唇裂 唇裂 ))

Anencephalus(( 无脑儿无脑儿 ))

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Immunological factors

Hypersensitivity (too strong) Immunodeficiency (too weak) Autoimmunity (misdirected)

Stress

Bad human relations

AnxietyAnxiety

Hypertension

Peptic ulcer

Heart disease

Depression

Cancer

……

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Psychological Factors

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Be joyful!

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Be forgiving!

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Mercy for the weak!

2.2 Conditions (条件）

Natural conditionWeatherGeology (location)

Prostate and breast cancer – high in the USLiver cancer – high in China

Physical conditionTirednessHypertension – easy to get myocardial infarction

Social conditionLaborHygiene Life style

Factors that by themselves are not sufficient to cause a disease but could influence the process or severity of disease.

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Conspectus of DiseaseConspectus of Disease

Concept of health and diseaseConcept of health and disease

Etiology of diseaseEtiology of disease

Pathogenesis of diseasePathogenesis of disease

Outcome of diseaseOutcome of disease

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Pathogenesis of Disease

The study of the rules and mechanisms underlying the development of the disease.

How the pathological agents cause disease?

How the disease develops?

3.1 General Rules of Disease 3.1 General Rules of Disease Development Development

Disruption of homeostasisDisruption of homeostasis

Alternation of cause and effectAlternation of cause and effect

Damage and anti-damageDamage and anti-damage

Local-systemic relationshipLocal-systemic relationship

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Four RulesFour Rules

3.1.1 Disruption of Homeostasis3.1.1 Disruption of HomeostasisWhat is homeostasis?What is homeostasis?Homeostasis (Homeostasis (homeohomeo = similar; = similar; stasisstasis = standing still) = standing still) refers to the process whereby the internal environment refers to the process whereby the internal environment tends to remain balanced and stable, which is required tends to remain balanced and stable, which is required for optimal functioning of the organism. for optimal functioning of the organism.

ExamplesExamplesTemperatureTemperaturepHpHBody fluidsBody fluidsElectrolytesElectrolytesOxygen levelOxygen level

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3.1.2 Alternation of Cause and 3.1.2 Alternation of Cause and Effect Effect ( (因果交替因果交替 ))

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Cause 1

Effect 1Cause 2

Effect 2Cause 3 ……

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Trauma

Hemorrhage

Blood volume↓

Blood pressure↓

Sympathetic nerve ↑

Vasoconstriction

Hypoxia

Microcirculation blood clotting

……

Vicious cycle

Example

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3.1.3 Damage and Anti-damage3.1.3 Damage and Anti-damage ( (损伤与抗损伤损伤与抗损伤 ))

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• Inter-connected, fighting.

Characteristics

• Balance determines disease

development.

Damage Anti-damage

Worse

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• Inter-connected, fighting.

Characteristics

• Balance determines disease

development.

Damage Anti-damage

Better

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• Inter-connected, fighting.

Characteristics

• Balance determines disease

development.

• Interchangeable.

Damage Anti-damage

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Trauma

Hemorrhage

Blood volume↓

Blood pressure↓

Sympathetic nerve ↑

Vasoconstriction

Hypoxia

MC blood clotting

……

Anti-damage → Damage

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3.1.4 Local-Systemic Relationship3.1.4 Local-Systemic Relationship

Inflammation (Furuncle) Inflammation (Furuncle) ((LocalLocal))

InfectionInfection

Fever Fever ↑↑WBCsWBCsSepsisSepsis((SystemicSystemic))

3.2 Fundamental Mechanisms of 3.2 Fundamental Mechanisms of DiseasesDiseases

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1)1) Neural mechanismNeural mechanism(( 神经机制神经机制 ))

22)) Humoral mechanismHumoral mechanism(( 体液机体液机制制 ))33)) Cellular mechanismCellular mechanism(( 细胞机制细胞机制 ))

44)) Molecular mechanismMolecular mechanism(( 分子机分子机制制 ))

Four MechanismsFour Mechanisms

Neural Mechanism Neural Mechanism (( 神经机制神经机制 ) )

◆ ◆ Rabies Rabies

virusvirus

VaccineVaccine

RabiesRabies

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◆◆Type B Encephalitis Virus Type B Encephalitis Virus Destroy Destroy CNS CNS Type Type

B Encephalitis B Encephalitis

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Humoral Mechanisms (Humoral Mechanisms ( 体液机体液机制制 ))

Humoral factorsHumoral factors

Hormones (estrogen, androgen, etc)Hormones (estrogen, androgen, etc)

Chemical mediators (histamine, Chemical mediators (histamine,

prostaglandins, etc)prostaglandins, etc)

Cytokines (ILs, TNFs, IFNs)Cytokines (ILs, TNFs, IFNs)

Humoral MechanismHumoral Mechanism

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Endocrine

Paracrine

Autocrine

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Cellular MechanismsCellular Mechanisms

Non-selective damageNon-selective damage

Direct damage to the cellDirect damage to the cell

(Strong acid or alkali)(Strong acid or alkali)

Selective damageSelective damage

Damage to cell membrane function (ion Damage to cell membrane function (ion

pump)pump)

Damage to the organelle (mitochondria)Damage to the organelle (mitochondria)

Damage to the cellDamage to the cell

Cell membrane damageCell membrane damage

Lysosome Lysosome damagedamage

Mitochondria damageMitochondria damage

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Receptors

Cell surface markers

Cytoskeleton (structural proteins)

Enzymes (kinases, phosphatases, etc)

Pumps

Channels

Molecular Mechanism (Molecular Mechanism ( 分子机分子机制制 ))

（（ Molecular Pathology (Molecular Pathology ( 分子病理学分子病理学 )) ） ）

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Enzyme deficiency:

Glucose-6-phosphate Glucose

Molecular Mechanism (Molecular Mechanism ( 分子机分子机制制 ))

G6PDH ↓↓

Glycogen Storage Disease(Liver)

Glucose-1-phosphate

Glycogen

Example

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Conspectus of DiseaseConspectus of Disease

Concept of health and diseaseConcept of health and disease

Etiology of diseaseEtiology of disease

Pathogenesis of diseasePathogenesis of disease

Outcome of diseaseOutcome of disease

5858

Outcome (Fate) of DiseaseOutcome (Fate) of Disease

Recovery Death

Complete recoveryIncomplete recovery

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Complete recovery

The best outcome of a disease.

The pathologically altered metabolism, structure and function are completely restored.

The symptoms and signs disappear entirely.

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Incomplete recovery

The main symptoms disappear but pathological changes still exist.

Sequela ( 后遗症 ) brought about by the compensatory response to maintain a relatively normal activity.

Heart disease Cardiac ventricular hypertrophyRheumatic feverDamage to the heart valvePolio Paralysis

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Death

Traditional concept

Cessation of heart-beats

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Death

A state of prolonged irreversiblecessation of all brain activities.

Modern concept

*Sign of death ━ brain death

6363

Irreversible coma

Absence of spontaneous respiration

No brain stem reflex

Flat EEG (brain wave)

Persistence of these signs for 30-60

min and for 6 h after coma

Criteria of brain death

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Saving medical resources

Having proper donors for organ

transplantation

The Significance of Brain Death Criteria