Pathophysiology

(BMS 518)
Dr. Tom Brady
Professor and Chairman of the
Department of Biomedical Sciences
 Health versus Disease
 Health: the state of an organism when all
body systems are functioning optimally,
without evidence of disease or abnormality.

 Disease: a state of an organism in which one

or more body systems are not functioning
optimally thereby resulting in abnormal
physiology.
 Health and Disease
 Health is often viewed as an equilibrium
between the many stresses/injuries that our body
cells/tissues are constantly subjected to, and the
ability of the body’s adaptive/defen- sive/repair
mechanisms to deal effectively with these
injuries.

 The body’s ability to adapt to these injuries will

therefore determine the individuals status
regarding health and disease.
 Examples of Stresses/Injuries
 infectious agents (b, v, f, p)
 chemical toxicity (endogenous/exogenous)
 physical agents (heat/cold, radiation, pressure)
 tissue hypoxia (ischemia….)
 internal mechanical stress (blood pressure, tumor)
 trauma
 DNA damage
 nutritional deficiencies
 genetic/chromosomal abnormalities
 Adaptation/Defense/Repair
Mechanisms
 immune system
 chemical detoxification/excretion systems
 DNA repair enzyme systems
 inflammatory response
 tissue healing/regeneration
 heat-shock response (i.e. stress proteins)
 apoptosis
 hemoglobin oxygen release in hypoxia
Basic Epidemiology
 Life Expectancy (U.S.)
 In the year 2008: females ~80, males ~76

 In the year 1908: ~47 years old???

 In the year 10,008 BC: ~35???

 In the year 2108 AD: ~???

Life Span vs. Maximal Life Span
 Whereas life expectancy refers to an average
within a population (e.g. the U.S.), life span
refers to how long an individual lives.

 Maximal life span refers to the longest period

that an individual of a particular species has
lived. What is the maximal life span for
humans on Planet Earth? Is this immutable?
Major Causes of Death in 2008 in All
Age Groups (U.S.)
 heart disease
 cancer
 stroke
 pulmonary disease
 infectious diseases
 diabetes
 kidney disease
Major Causes of Death in 1908 in All
Age Groups
 infectious diseases (by far #1)
 heart disease
 cancer
 stroke
 What has Changed Since 1908?
 antibiotics
 vaccines
 public health policies (sewage, food, water)
 personal hygiene
 medical advances
 alteration personal behavior
Basic Terminology in
Pathophysiology
 Terminology
 Pathophysiology may simply be defined as
the study of disease mechanisms at the cellular
and molecular levels.
 Pathogenesis is related to this in that it refers
to the specific steps involved in the
development of the disease process (e.g. HIV
infection -> immune system decline -> AIDS).
 Terminology
 Lesion: the actual tissue injury (e.g. infarct,
cut, DNA damage, tumor…)

 Etiology: the cause of the disease (HIV/AIDS)

 Idiopathic: the cause of the disease is

unknown.
 Terminology
 Acute disease: a disease characterized by
rapid onset, short duration and is generally of a
severe nature (e.g. acute hepatitis).

 Chronic disease: a disease characterized by a

relatively slow onset, long duration and
generally not as severe as acute disease (e.g.
chronic hepatitis).
 Terminology
 Congenital disease: a deformity resulting from abnormal
gestational development (i.e. a birth defect).

 Familial disease: a disease that is expressed within a family

(e.g. diabetes, breast cancer).

 Genetic/inherited disease: a disease that is inherited directly

through specific genes (e.g. cystic fibrosis, hemophilia, sickle
cell anemia).

 Disease predisposition: an increased likelihood of expressing

a particular disease.
 Terminology
 Morbidity: refers to a diseased state or a
decrease in life expectancy.

 Mortality: refers to causing death.

 Classification of Disease Types
 Inherited/genetic
 Congenital
 Metabolic
 Degenerative
 Neoplastic
 Immunologic
 Infectious
 Physical/chemical agent induced
 Nutritional deficiency
 Psychogenic
 Iatrogenic
 Idiopathic
 Review of Basic Cell and
Tissue Biology/Biochemistry
Review of Cell Structure/Function
 Review of Major Bio-molecules
 Carbohydrates

 Lipids

 Proteins

 Nucleic acids
Glucose
Lipid-Triglyceride
Lipid-Cholesterol
Proteins
DNA
DNA
DNA versus RNA
 Review of Cell Processes
 Movement of materials into and out of cell

 Cell energetics (ATP/oxidative phosphorylation)

 Protein synthesis (transcription/translation)

 Cell division via mitosis (cell cycle)

 Cell division via meiosis

Movement of Molecules Across a
Biological Membrane
ATP Production
Protein Synthesis via Transcription
and Translation
Mitosis
Cell Cycle
Meiosis
 Four Major Tissue Types
 Epithelial

 Connective

 Muscle

 Nerve
Epithelial Tissue
Connective Tissue
Muscle Tissue
Nerve Tissue
Cell/Tissue Injury, Death,
Mechanisms/Responses
Cell/Tissue “Targets” for Injury
 Cell membrane integrity
 Organelle membrane integrity
 ATP generation
 Protein synthesis
 Integrity of DNA
 Cytoplasmic calcium concentration
 Cell oxidant/anti-oxidant equilibrium
Ischemia-Related Damage
Cytosolic Calcium Disturbances
Oxidant/Anti-Oxidant Homeostasis
Reversible vs. Irreversible Cell
Injury
 Factors in Injury Response
 Specific type of injury (hypoxia, radiation…)

 Severity of injury (degree, dose…)

 Specific cell types involved (neurons, epithelial…)

 Duration of injury ( acute vs. chronic exposure)

 Health status of cell(s) at time of injury (hypoxic..)

Cell Death Mechanisms
Induction of Apoptosis
Responses to Injury Other Than Cell
Death
 Fatty changes (steatosis)
 Calcification
 Atrophy
 Hypertrophy
 Hyperplasia
 Metaplasia
 Dysplasia
 Neoplasia
Tissue Responses
 Tissue Adaptations
 Metaplasia: abnormal transformation of a normal
tissue type with another normal tissue type (e.g.
squamous metaplasia in smokers).
 Dysplasia: abnormal tissue development (e.g.
myeloid dysplasia).
 Aplasia: defective development or absence of a
tissue or organ (e.g. aplastic anemia).
 Neoplasia: abnormal tissue growth of a benign or
malignant nature (e.g. a tumor).
Cell Aging
 Cellular Aging/Senescence
 Multicellular organisms all show a progressive and
irreversible physiological decline that is referred to as
senescence or aging.

 This is a multifactorial process resulting from both

extrinsic and intrinsic factors which result in an
accumulation of cellular alterations which, in turn,
results in diminished cell/tissue function and
eventually senescence and death.
 Structural Changes in Aging
Cells
 Lobed nuclei
 Mitochondrial vacuoles
 Decreased ER
 Distorted Golgi
 Accumulation of pigments (e.g. lipofuscin)
 Micro damage to cell membranes
 Functional Changes in Aging Cells
 Decrease in oxidative phosphorylation
 Decrease in protein synthesis
 Decreased nutrient uptake
 Decreased repair ability, including DNA repair
 Decreased antioxidant activity
 Increased production of free radicals