Pathophysiology 101-823

Unit 1

Basic Concepts of Health & Disease

Paul Anderson 2011

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Learning Objectives

• Describe health and disease in terms of the homeostatic model of the human body.

• Explain how disease of cells, tissues or organs affects homeostasis and relate selected disequilibria to their diseases of origin.

• Explain how homeostatic responses may cause clinical manifestations of disease.

• Define the terms etiology, physiology, pathology, pathophysiology.

• Define etiological factors and distinguish between genetic and environmental factors.

• Define multifactorial, congenital and acquired, infectious, contagious (communicable) diseases.

• Define clinical manifestations, signs, symptoms, syndrome.

• Describe the process of diagnosing diseases and requirements of good lab tests.

• Describe the clinical course & appearance of disease, defining the terms acute and chronic diseases, preclinical, clinical, subclinical and carrier.

• Compare how a disease is studied by means of epidemiology and by the study of its pathogenesis.

• Define mortality, morbidity, incidence and prevalence of diseases.

References: Porth, Pathophysiology, Ch. 1 pp. 2 - 9, Ch. 9 (Homeostasis)

Porth, Essentials, Introduction, pp. xxxi-xxxv, Ch. 7 (Homeostasis).

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Disease and Health

What is Health?

• Health can be defined as a state of complete physical, mental and social well being, not merely the absence of disease and infirmity (World Health Organisation WHO 1948).

What is Disease?

• Disease can be defined as a recognisabledeviation from the normal structure and functioning of a body system or its components.

• Diseases may also be called Disorders.

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How Disease affects Homeostatic Mechanisms

Disease affects Homeostatic mechanisms in 4 ways

A. Disease Disturbs Homeostasis, causing Disequilibria.B. Disease causes a Failure of Homeostatic Adaptation

i.e. failure to restore homeostasis.C. The diseased body does adapt to disequilibria caused

by disease through its homeostatic mechanisms, but sometimes Overcompensates to cause Secondary Disease.

D. Compensatory Homeostatic Responses can produceClinical Manifestations of an existing disease.

Homeostatic Control Systems are Sensitive to Changes in the Internal Environment & produce Compensatory Negative Feedback Responses.

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A. Disease Causes Disequilibria

Disease disturbs Homeostasis Producing a State of Disequilibrium

Disease cells tissues organs

Loss of homeostatic function

damages

Disequilibrium

Glomerulonephritisepithelial cells Glomerular Epithelium Kidney

•Filtration of blood•Urine formation:

Hypertension

Heart Disease Causes Disequilibrium

Coronary Heart Disease (CHD)

Heart cells die(Myocardial Infarction)

Ventricular muscle weakened

Heart’s pumping ability declines(cardiogenic shock -a dangerous complication of CHD)

Reduced cardiac outputHypotension

Note: CHD = Coronary Artery Disease - CAD

Examples of Disequilibria

DISEQUILIBRIUM FACTOR AFFECTED POSSIBLE CAUSES

Fever - elevated body temp. Viral/bacterial infection

Edema - elevated body [H20] kidney disease(causing fluid retention)

Hypertension - elevated ABP CV or kidney disease

Hypotension - lowered ABP hemorrhage or heart disease

Hyperglycemia - elevated plasma [glucose] -"blood sugar” Diabetes mellitus

Hypoxia - lowered tissue pO2 Respiratory or CV disease

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B. Disease causes a Failure to Maintain Homeostasis

• Diseased organs, tissues, cells cannot properly adapt to environmental changes and maintain homeostasis.

• With disease there is therefore a tendency for persistence of disequilibria that may lead to other disequilibria and secondary disease.

• Thus in Diabetes mellitus, chronic hyperglycemia with disordered metabolism causes further disequilibriasuch as dehydration and ketoacidosis.

• Complications of diabetes from secondary diseasesare superficial infections and diseases of the eyes, kidneys, nerves and arteries.

Disturbance to Homeostasis

Adaptation

Health Diseasenormal abnormal

Adaptations to Homeostatic Imbalance in Health & Disease

•Healthy Adaptation is Homeostatic, restoring normal equilibrium and health.

•In Disease there is a Failure of Normal Adaptationcausing persistent disequilibrium leading to other disequilibria and secondary disease.

•Disequilibrium removed•Homeostasis restored

•Disequilibrium remains•Further disequilibria may occur•Secondary disease may occur

Local Adaptations to Environmental Change

Increased Workload on

Heart

Local (Cellular)Adaptation

Health Disease

Normal Hypertrophy increases cardiac output & reduces stress on heart muscle

Abnormal Hypertrophy may cause decline in cardiac output

Local Adaptations to Environmental Change are Cellular•myocardial hypertrophy in an athlete (normal): cells increase insize uniformly.•myocardial hypertrophy in hypertensive patient (abnormal): cellsincrease in size abnormally (width more than length)

Exercise causes increased oxygen demands by muscles

Chronic hypertension means heart must generate higher pressure to eject blood

Porth fig 5-2

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Systemic Adaptations to Environmental Change

Hyperglycemia

Systemic Adaptation

Health DiseaseNormal blood sugar level restored

•Hyperglycemia remains•Further disequilibria may occur (e.g. ketoacidosis, dehydration)

•Secondary disease may occur (in skin, eyes, kidneys, nerves, arteries)

Systemic Adaptations to Environmental Change involvesHomeostatic Control Systems

• Restoring the blood sugar level to normal after a meal via the insulin response in a healthy person.

• Failure to restore the blood sugar level in the absence of an insulin response in a diabetic person and shifting of metabolism to fat & protein breakdown.

Blood sugar level rises after a meal

Blood sugar level is high due to pancreatic β cell dysfunction or because of insulin resistance

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C. Disease Caused by Homeostatic Overcompensation

The body adapts to stress from one disease through its homeostatic mechanisms, sometimes Overcompensating to cause a Secondary Disease

Chronic Systemic Hypertension

Increased workload on left ventricle

Left ventricle hypertrophies

Cardiac Arrythmia

Decreased cardiac output

In this example a local (cellular) adaptive response of cardiac muscle results in overcompensation.

Overcompensation may eventually cause

Porth fig 5-2

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D. Homeostatic Responses Produce Clinical Manifestations

Stimulus Receptor

Integrating Center

EffectorCompensatory Homeostatic Response

Negative feedbacknormallyturns off stimulus

ClinicalManifestation of Disease

Disease

Disequilibrium

Homeostatic Responses can cause Clinical Manifestations of a Disease

acts as activates

Sendsmessage to

Sends message to

causes

Compensatory Responses may Persist in Disease State giving Clinical Manifestations

may cause

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Clinical Manifestation of Hemorrhage

Hypotension Arterial Baroreceptors

Cardiac Accelerator Center of hind brain

TachycardiaClinical Manifestation (Sign) of Disease

Negative feedback

Disease or Injury

Blood Volume

Homeostatic responses can causeClinical Manifestations of a Disease.

Compensatory Homeostatic ResponseIncreased heart activity

Causes acute hemorrhage

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Definition of Pathophysiology - 1

• Pathology is concerned mainly with studying the characteristics of diseased organs & tissues.

• Physiology is the study of normal body function.

• Pathophysiology is the study of the physiological changes associated with disease.

Pathophysiology is a combination of Pathology and Physiology

Pathophysiology is the Physiology of Disease

Disturbance to Homeostasis

Adaptation

Health Disease

Local (Cellular)

Systemic (Homeostatic Control System)

Pathology

Pathophysiology

Physiology

normal abnormal

studies Studiesdiseased organs & tissues Studies the

physiology of disease

combination of pathology & physiology

Definition of Pathophysiology - 2

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Focus & Usefulness of Pathophysiology

Since structure and function go together pathophysiologymust deal with

• Structural changes due to disease in organs, tissues and cells

• Effects these structural changes have on body functions.

Therefore Pathophysiology

• Focuses on the mechanisms underlying disease but also

• Provides a background for therapeutic health caremeasures and practices.

Pathophysiology is the Physiology of Disease

Therefore Pathophysiology helps nurses understand disease processes & how nursing interventions can restore health.

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What Pathophysiology Includes

Pathophysiology studies the disease in the individual so includes:

• Etiology

• Clinical Manifestations & diagnosis

• Pathogenesis & Clinical Course of disease

• Treatment & Management of Disease

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Etiology

• Environmental Factors– Microorganisms, viruses, bacteria & other parasites– Physical factors, physical trauma, radiation, etc– Chemical agents, drugs, toxins– Nutritional excess or deficit– Psychological stressors (causing maladaptive responses to stress

e.g. Post Traumatic Stress Disorder)

• Genetic Factors– Inherited gene or chromosomal mutations (alterations to DNA)

Etiology is the the study of the causes of disease

�Etiological factors are factors that cause disease �Etiological factors may be Environmental or Genetic

Diseases may be genetic, environmental or multifactorial(caused by a combination of genetic & environmental factors).

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Genetic Factors may cause Genetic Disease or a Genetic Predisposition to develop a disease.

Etiology: Genetic & Multifactorial Disease

• Genetic Disease may be caused by a single gene defect(e.g. cystic fibrosis, sickle cell anemia), by many genes or by a chromosomal defect (e.g. Down syndrome).

• Diseases involving a Genetic Predisposition are associated with many genetic factors (inheritance of certain genes) and environmental factors (lifestyle etc.) called “Risk Factors” .

• These diseases are therefore called MultifactorialDiseases and include some congenital diseases, heart disease, diabetes mellitus 2, hypertension, cancer, manic depressive psychosis (bipolar disorder) and schizophrenia.

Most Diseases are Multifactorial

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Congenital vs Acquired Conditions

Environmental Factors may cause congenital or acquired disease.

• Congenital Conditions are present at birth.

• Congenital Conditions may be genetic (e.g. cystic fibrosis) environmental (e.g. fetal alcohol syndrome, AIDS) or be multifactorial (e.g. cleft lip or palate, congenital heart disease).

• Acquired Conditions are caused by environmental factors after birth, such as trauma, infection, malnutrition, lack of oxygen.

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Infectious Diseases

• Infection is the presence and multiplication of a living organism, virus or protein in or on a host organism.

• Note - not all microorganisms are detrimental to health (a normal microflora in the body is important for health).

• Agents of infectious disease (pathogens) include• prions (infectious proteins)*• viruses ( e.g. flu, cold, AIDS)• bacteria (e.g. salmonella – typhoid-TB)• rickettsiae (e.g. typhus)• chlamydiae (e.g. some STDs),• fungi (e.g. athletes foot)• animal parasites (e.g. Plasmodium, cause of malaria).

• Contagious (Communicable) Diseases are infectious diseases spread directly from person to person, e.g. measles (rubeola- a viral disease).

*Prions cause transmissible neurogenerative diseases, e.g. Creutzfeldt-Jacob disease

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• Preclinical: not evident but destined to progress to clinical status - cantransmit infection to others, e.g. hepatitis B, HIV but may not show immune response yet.

• Clinical: shows signs and symptoms & positive test for antibodies.

•Sub-clinical: If a disease is inactive (dormant). Most cases of Tuberculosis- TB are “latent” TB: immune system is activated so person gives a positive immune response test result.

• A Carrier for an infectious communicable disease is an individual who harbours the pathogen and can infect others but may not show signs of the disease (e.g. preclinical Hepatitis B, HIV). Individuals with Latent TB cannot infect others so are not carriers.

Appearance of Infectious Diseases: Four States

Preclinical

Clinical Manifestation

of Disease

Clinical SubClinicalbecomes

No Clinical

Manifestation of Disease

carriermay act as

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Clinical Manifestations of Disease - 1

Clinical Manifestations are various indications (signs and symptoms) that a patient is ill.

• Symptom: subjective complaint noticed only by the person with the disorder, e.g. feeling cold, tired, pain.

• Sign: manifestation noted or measured by medical observere.g. shivering, change in body temperature, swelling.Both may be related to the disorder or be indicators of the body’s compensatory mechanisms in action.

Disease is any disruption of normal structure or function of organ or system that is manifested by a characteristic set of signs and symptoms.

A Syndrome is a group of typical signs and symptoms associated with a disease enabling a diagnosis to be made.

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Clinical Manifestations of Disease - 2

Signs

Syndrome

Symptoms

Clinical Manifestations of Disease

Disease

Diagnosis

Compensatory Homeostatic Responses

may cause

causes

causes

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Diagnosis of Disease - 1

• Diagnosis is the designation of the nature of the disease.

- Involves careful consideration of history (symptoms) and physical examination (signs) .

- Requires determination of individual “normality” by taking into account age, sex, race, lifestyle, family history, etc.

- Often relies on information from epidemiology and pathogenesis.

• Diagnosis usually requires several pieces of information such as laboratory tests.

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Diagnosis of Disease - Lab Tests

DiagnosisLaboratory Tests

•Reliable•Valid•Sensitive•Specific

- Reliable: test can be repeated with same result - Valid: test is a true measure of the disease- Sensitive: test gives no false -ves - delays treatment - Specific: test gives no false +ves - creates stress

must be

Positive

Negative

Present Absent

True

Positive

False

Negative

True

Negative

False

Positive

From Porth, fig 1-1

DISEASE

TESTRESULT

•Test Sensitivity gives %

of true +ves (persons

with disease).

•Test Specificity gives %

of true -ves (those with

no disease)

Pathogenesis: The Progression of Disease in Individuals

Pathogenesis is the development of a disease in a person, the sequence of cellular and tissue events following contact with etiological factorse.g. Inhalation of airborne bacteria from person with active TB causes cell mediated immune response that walls off infection in lungs.

•Pathogenesis involves studying morphological changes - seen in a biopsy, e.g. a lesion, using histology- seen with medical imaging e.g. X rays, CAT scans

e.g. TB nodules (granulomas) seen in lung X ray

•Pathogenesis describes how the disease process evolves and explains the clinical manifestations of the disease.

Diseases in individuals are studied in Pathology and Pathophysiology.

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Clinical Course of Diseases

• Acute Disease is severe but self limiting, e.g. measles (rubeola).

• Chronic Disease is continuous long term e.g. malaria, TB.

Chronic Disease is persistent - sometimes for life, often characterized by flare ups (with exacerbation followed by remission).

Clinical Course is the pattern of development of a disease in an individual: it may be Acute or Chronic.

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The Study of Disease in Populations

• Epidemiology was used originally to stop outbreaks of infectious disease during epidemics.

• Epidemiology is now used to study

- how disease spreads, how to control and eliminate it as well as- the risk factors for multifactorial diseases including

age, diet, race, lifestyle, location.

- the Natural History of Disease.

Epidemiology is the study of Disease in Populations

•The Natural History of Disease is its progression and projected outcome in general without intervention (e.g. 80% of persons with hepatitis C virus, for which there is no vaccine, tend to develop a chronic infection).

•Natural History provides data for preventative measures and prognosis.

•Prognosis is the probable outcome/ prospect of recovery in individuals and depends on epidemiological as well as personal data.

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Morbidity Rates include• Incidence: % of new cases in a population at risk

in a specific time• Prevalence: % of people in population who have the disease at a given time

Epidemiology

Epidemiology measures disease frequency,

through the Incidence and Prevalence of disease in

populations using statistics

• Mortality (death) rates

• Morbidity (presence of disease & how disease affects person’s life over long term).