Chapter 1. conspectus of disease

Yu-Hong Jia, Ph.D

Department of pathophysiology

Dalian medical university

• concept of disease• etiology of diseas• pathogenesis of disease• outcome of disease.

1. Concept of disease

• Disease: is referred as aberrant manifestation of deregulated homeostasis caused by harmful agents in a certain condition.

•A certain condition

•Cause of disease

•The interation of damage and anti-damage

•A series of funtional, metabolic and structural alterations in the body

•Clinical Signs and symptoms

Cold, low resistance

Flu virus

Increased immunoresponse

Changes of Glucose, fat and protein metabolism

Alteration of cardiopulmonary function

Catarrh(nose running,sneeze,)Cough, fever,

Flu

Health Former definition of health:The state of the organism when it functionsoptimally without any evidence of disease.

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

Sub-health

• 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.

2. Etiology of disease.

Contributing factors that cause disease.

Causative factors

Predisposing factors

Precipitating factors

• Extrinsic factors• Intrinsic factors

(1) Causes of disease (causative factors)

– Biological agents: microorganisms and

parasites– Chemical agents: non-specific or specific– Physical agents: mechanical injuries,

extremes of temperature, electricity and radiation. Participate in initiation but not development of disease. Non-specific injury.

– Nutritional imbalance: excesses or deficiencies of nutrients.

• Extrinsic causes

• Intrinsic factors

– Genetic factors: single or polygenic mutation– Congenital factors: abnormal embryonic

developmental error– Immunological factors: the immune response is

deficient or inappropriately strong or misdirected– Psychological factors: Anxiety, strong or persistent psychological stress.

(2) Predisposing factor

• influence the susceptibility or resistance to certain disease.– Genetic constitution – Physiological diathesis– Psychological characteristics

(3) Precipitating factor

• intensify the roles of causative factors and promote the onset and development of diseases.– Natural condition e.g. weather condition,

geographical environment– Physical condition e.g. physical or mental

fatigue or anxiety– Social condition e.g. poor labor and hygiene

condition

• Pathogenesis of disease refers to the rules and mechanisms underlying the development or evolution of the disease.– General rules for pathogenesis of disease– Fundamental mechanisms for disease

3. Pathogenesis of disease

(1) General rule for pathogenesis of disease

1) Disruption of homeostasis2) Process of damage and anti-damage3) Reversal rule of cause and result4) Correlation between systemic and local

regulations

1) Disruption of homeostasis

• Homeostasis denotes the process whereby the internal environment of an organism tends to remain balanced and stable, which is required for optimum functioning.

• Disruption of homeostasis by harmful agnents may cause disease.

2) Process of damage and anti-damage

• Any disease is a process full of battle between damage and anti-damage.

• The contrast between strength of damage and anti-damage determine the development of a disease.

reninangiotensinogen

Angiotensin ⅠAngiotensin Ⅱ

Increased water and sodium reaborption

↑effective circulatory blood volume

hemorrhage

↓effective circulatory blood volume

↓Renal artery pressure

↓GFR→↓Na+ at macula

densa

↑Sympathetic nerve

glomerulus

Juxtaglomerular cells

Converting enzyme

+

Organ ischemia, dysfunction

damage

(JG cells)

Adrenal cortex

3) Reversal rule of cause and result

Primary Primary causecause

Result Result (cause)(cause)Further Further alteration alteration

Secondary Secondary alterationalteration

(cause)(cause)

(+)(-)

Severe hemorrhage

↓Cardiac output

↓Blood pressure

↑Symphathetic nerve

↑catecholamine

Constriction of Microartery & micro

vein

Tissue hypoxia

acidosisRe-open of

capillaryBlood stagnant in microcirculation

↓Blood volume returned to heart

+

↓↓BP

v i co

us

i

c yc l e

4) Correlation between systemic and local regulations

Systemic alteration

Local alteration

disease

Neural-humoral regulation

Neural-humoral regulation

Furuncle, Local

inflammation

Systemic reaction of fever and elevated

leukocyte

Systemic metabolic disorder caused by diabetes mellitus

furuncle

(2) Fundamental mechanisms for diseases

1) Neural mechanism2) Humoral mechanism3) Cellular mechanism4) Molecular mechanism

• Alteration of neural system is tightly related with pathogenesis of disease.

• The alterations of neural system induced by pathogens include:– Direct injury of neural system (e.g. type B encephalitis)– Change of neural reflex (e.g. Parkinson’s disease)– Change of metabolism of neural cells (e.g. Alzheimer’s

disease)• Among neural mechanism, sympathetic system is

of important role.– Sympathetic nerve participates in many pathologic

processes, e.g. edema, stress, shock

1) Neural mechanism

Sympathetic system Distribution of sympathetic system• Organs of head, neck, trunk, & external genitalia• Adrenal medulla• Sweat glands in skin• Arrector muscles of hair• All vascular smooth muscle

2) Humoral mechanism

• Humoral dysfunction indicates the alterations in number and activities of some humoral factors.

• Humoral factors include:– Hormones (i.e. Renin-Angiotensin-Aldosterone system, A

DH)– Chemical mediators (i.e. histamine, prostaglandin)– Cytokines (i.e. interleukines, tumor necrosis factors)

• Function manner of humoral factors include:– Endocrine– Paracrine– Autocrine– intracrine

Decreased blood pressure

Angiotensin Ⅰ

Angiotensin Ⅱ

Aldosterone

Decreased urine volume conserves blood pressure

Renin

Regulation of Renin-Angiotensin-Aldosterone system

OsmoreceptorsIncreased osmotic press

ure

Baroreceptors (aortic arch, carotid sinus) Decrease

blood pressure

Neurosecretory cell

Posterior pituitory

vasoconstriction

Blood vessel

Increased blood volume and

increased blood pressure

kidney

Increased reabsorption of water

ADH

Regulation and effect of ADH

Endocrine action: the hormone is distributed in blood and binds to distant target cells.Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.Autocrine action: the hormone acts on the same cell that produced it.

Manners with which humoral factors exerts its function

Neural-humoral regulation

endocrine glands

neural system

one loop of neural system

effect

• For example:Sympathetic nerve excites→increased secretion of epinephrine and norepinephrine by medulla of adrenal gland → α、 ß receptors excitation in cardiac vascular system → heart rate↑ and blood vessels contract → BP↑

3) Cellular mechanism

• Cell damage – Some pathogens destroy the cells with no selection, i.e. strong

acid and alkali– Others attack cells selectively, i.e. hepatitis virus

• Selective damage of cells involves: cell membrane Na+ pump( Na+-K+-ATPase) → cellular edema Ca2+ pump(Ca2+-ATPase) → Ca2+ overload

organelles mitochondrium→ ATP↓ lysosome→ cell autolysis

4) Molecular mechanism

• abnormal alteration at molecular level – macro-molecule →nucleic acid, protein

• Molecular disease• i.e. sickle cell anemia

– micro-molecule

4. Outcome of disease.

• Recovery– Complete recovery : the pathological

alterations are perfectly restored and the signs and symptoms of disease disappear entirely.

– Incomplete recovery: the main symptoms disappear but some pathological changes are still there.

• i.e. myocardial infarction

• Death

Death

• The body as a whole stop working forever• The cessation of heartbeats was used as c

riterion of death before.• The accepted definition of death now is br

ain death.

Brain Death (WHO criteria)

• Cessation of spontaneous respiration• Irreversible coma• Absence of cephalic reflexes• Dilated or fixed pupils• Absence of any electrical activity of the

brain• Absence of brain blood flow

Significance for diagnosis of brain death

In favor of recording the time of death

Define the time to terminate for the rescue

In favor of organ transplantation

review• Concept of disease

– Disease※, health, sub-health• Etiology of disease

– Causative factors– Predisposing and precipitating factors

• Pathogenesis of disease– General rule

• Disruption of homeostasis• Damage and anti-damage• Alternation of cause and result• Correlation of System and local

– Fundamental mechanism• Neural mechanism• Humoral mechanism• Cellular mechanism• Molecular mechanism

• The alterations of neural system – Direct injury of neural system, i.e.

• Type B encephalitis– Change of neural reflex and metabolism of neura

l cells, i.e. • Exciting of sympathetic nerve → release of catechola

mine→biological effects; • Alzheimer’s disease →β-amyloid peptide accumulatio

n in brain cell

1) Neural mechanism

• alterations in number and activities of humoral factors.– Hormones (i.e. Renin-Angiotensin-Aldosterone sy

stem, ADH)– Chemical mediators (i.e. histamine, prostaglandi

n)– Cytokines (i.e. interleukines, tumor necrosis facto

rs)

2) Humoral mechanism

• Function manner of humoral factors include:– Endocrine– Paracrine– Autocrine– intracrine

3) Cellular mechanism

• Cell damage– cell membrane

• Na+ pump• Ca2+ pump

– Cell organelles• Mitochondrium• lysosome