Download General Principles of Pathophysiology Definition of basic terms

General Principles of
Pathophysiology
Introduction to
Pathophysiology
Walsh McDermott
Cecil’s Textbook of Medicine
Medicine is not a science but a learned
profession, deeply rooted in a
number of sciences and charged
with the obligation to apply them for
man's benefit
The Normal Cell Homeostasis
Cellular & Tissue Response to
Injury
The origins of pathological physiology
Claude Bernard (1813 – 1878) Introduction á l’
étude de la medicine expérimentale, 1865
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Younger than Pathological Anatomy
Experimental science
Integrative subject (genetics, biochemistry,
signal transduction, molecular, subcellular &
cellular aspects, etc.)
Disease
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The term disease, or nosological unit has a
very specific meaning in medicine
It implies a disorder that has a specific
cause, or etiology, from which one should
be able to derive its pathogenesis, or the
development of symptoms
An understanding of the disorder in these
aspect should lead one to specific
therapeutic strategies and measures, and
to prognostic conclusions
Definition of basic terms
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NOSOLOGY
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ETIOLOGY
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Health and disease, classification of diseases
Causes and conditions of pathological processes
and diseases
PATHOGENESIS
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The way from health to disease (regulation,
adaptation, defense systems)
Key terms
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Acute
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A condition with relatively severe manifestations but running
a short course
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Chronic
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Complication
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A condition that lasts for a long period of time
A new or separate process that may arise secondarily
because of some change produced by the original entity
Re-Convalescence
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The stage of recovery after a disease, injury, or surgical
operation
Who is ill and who is healthy?
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Health is the state of complete physical,
mental and social well-being and not merely
the lack of disease or physical defects
Life in harmony with their environment and
each other
WHO (1947, 1986)
Between health and disease
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The difference between physiological & pathological
is not that strict (blood clots)
Pathological processes (inflammation, fever,
oedema, etc.)
Pathological reactions and reflexes
Pathological findings
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Nosological units
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Diabetes
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Diabetes mellitus and diabetes insipidus
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Diabetes mellitus type I, II, other forms
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Classical:
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symptom, biochemistry diagnosis
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Asymptomatic stage of chronic diseases
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symptom, genomics diagnosis)
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Risk factors
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latent (incubation time)
prodromal
manifestation
outcome
symptom, patophysiology diagnosis
Subtypes of diabetes mellitus type II
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Stages of diseases
symptom diagnosis
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laboratory, biochemical abnormalities are not diseases
blood pressure is a special case
noninvasive imaging methods (USG, CT, NMR)
faulty genes
Framingham study, 1949 – 1974
Connection between epidemiological and
experimental results
Probability of the disease development or its
existence in asymptomatic form
Silent form of coronary heart disease
Non-diagnosed diabetes, hypertension, etc.
Glossary
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Disease Sum of deviation from normal structure or funktion of
any part, organ or systém (or combination of there) of the body
manifested by a characteristic set of symptoms and/or signs
and whose etiology, pathogenesis, and prognosis may be
known or unknown
Etiology The assignment of causes or reasons for phenomena
Pathogenesis The development or evolution of the disease. A
description of the pathogenesis includes everything that
happens in the body from the initial stimulus to the ultimate
expression of manifestation of the disease
Remission An abatement or decline in severity of the signs and
symptoms of a disease. If remission is permanent, we say that
the person is “cured”
Prognosis A forecast about the probable outcome of a disease;
the prospect of recovery from disease indicated by the nature,
signs, and/or the symptoms of the case
Glossary
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Pathogen An agent that cause disease
Morphologic changes The structural and
associated functional alterations in cells or
tissues that are eiter characteristuc of the
disease or diagnostic of the etiologic process
Sequela A condition caused by and following
a disease (pl. sequelae)
Glossary
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Exacerbation A relatively sudden increase in the
severity of a disease or any of the signs and
symptoms
Intercurrent Occurs during the course of an already
existing disease
Epidemic Disease occuring suddenly and affecting
numbers of people clearly of excess of normal
expectancy
Pandemic Epidemics that affect large geographic
regions, perhaps spreading worldwide
Glossary
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Pathophysiology The science of disordered function
Building Blocks of Life
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Amino Acids => Proteins
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Structure & Function
Information Transmission, energy storage
Simple Sugars => Polysaccharides
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Cellular Components
Energy Sources, structure
Fatty Acids => Lipids
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Structure, Energy Source
Membrane
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Nucleic Acids => DNA / RNA
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Cell, tissue
Sign Objectively identifiable aberration of the
disease, Fever, reddening of the skin, and palpable
mass are signs of disease
Symptom Subjective feeling of discomfort that can
be reported by the affected individual to the
observer. Nausea, malaise, and pain are symptoms
of disease
Syndrome A collection of different signs and
symptoms that occur together
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Phospholipid bilayer
Membrane proteins
Cytoplasm
Nucleus
Ribosomes
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Mitochondria
Endoplasmic Reticulum
Golgi Apparatus
Lysosomes
Cellular Functions
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Reproduction
Growth
Differentiation
Respiration
Secretion
Excretion
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Methods of Communication
Metabolism
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Catabolism
Anabolism
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Responsiveness
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Movement
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Endocrine
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Nervous
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Conductivity
General Response to Injury
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Atrophy
Hypertrophy
Hyperplasia
Dysplasia
Metaplasia
Neurotransmitters
General Response to Injury
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Cellular Adaptation
Hormones
Cellular Adaptation
Mechanisms of Cell Injury
Manifestations of Cell Injury
Cellular Death
Mechanisms of Injury
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Hypoxic
Chemical
Mechanical
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(e.g., trauma)
Infectious
Immunologic / Inflammatory
Apoptosis
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Physiological cell death
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a genetically encoded cell elimination program
which ensures an equilibrium between cell
proliferation and cell death
The initiation of apoptosis
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The proteins executing the apoptotic program belong to a family of
proteases called the caspases
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These proteins exist as inactive zymogens in all cells
Apoptotic Protease Activating Factor 2 (Apaf-2 or cytochrome C) and
Apoptosis inducing factor
Apaf-2 with the coafactors Apaf-1, Apaf-3 and dATP can activate
caspase-3
Members of Bcl-2 family (proto-oncogenes) act either to prevent or to
promote cell death pathways leading to apoptosis
Apoptosis related genes, such as p53, show high rates of mutations
in human cancers
Diseases related to enhanced apoptosis
Apoptosis
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Programmed cell death (PCD)
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Active, energy saving cell elimination mechanism
Without continuous signalling by growth factors,
hormones or cytokines cells undergo PCD
Diseases related to defective apoptosis
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Defective reversal of hyperplasia (dysmenorrhea, cardiomyopathy)
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Occurrence of metaplasia (in situ carcinoma)
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Development of tumors (carcinoma, non-small-cell lung carcinoma)
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Resistance to cytotoxic treatment
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Residual disease after anti-cancer therapy
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Lymphoproliferative disorders (defect in Fas receptor)
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Auto-immune diseases (lupus erythematosus)
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Deficient resolution of inflammation (keloid formation, pulmonary fibrosis, liver
cirrhosis)
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Altered keratinization (eczema, psoriasis)
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Viral infections (adenovirus, baculovirus)
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Congenital abnormalities (syndactylism, hare lip, hypospadias, neural tube
defect, phocomelia)
Necrosis
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accidental cell death
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Wasting disease (M. Hodgkin, carcinomatosis, tuberculosis)
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Acquired immune deficiency syndrome (AIDS)
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The cell membrane loses its selective permeability
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Presenile atrophy (Macula degeneration, Retinitis pigmentosa,
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This leads almost instantaneously to
Presbyacusis, Osteoporosis, Lung Emphysema)
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Ineffective hematopoiesis (Myelo Dysplastic Syndrome, Aplastic Anemia)
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Neurodegenerative diseases (Alzheimer, Amyotrophic Lateral Sclerosis,
Parkinson disease, Alcoholic brain damage, Fetal alcohol syndrome)
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Ischemic damage (Tubular necrosis, Renal cortical necrosis, Myocardial
infarction, Cerebral infarction)
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Mucosal erosions (steroids, NSAID's, Reye disease)
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Insulin dependent diabetes mellitus
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Ulcerative colitis, Crohn's disease
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swelling of the cell and its organelles, including the
mitochondria, and
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leaking of the cellular contents into the extracellular space.
Activation of enzymes such as hydrolases,
phospholipases, proteases, RNases, and DNases
results in further degradation of membranes, proteins,
RNA and DNA, which accelerates the cellular and
nuclear disintegration
Necrosis
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Occurs in whole fields of damaged cells,
where the leaked cellular debris elicits an
inflammatory reaction in the adjacent tissue
Mechanisms of Cell Injury
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Ischemia
Activated Oxygen Species (O2.-, H2O2, OH. )
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Ischemic and Hypoxic Injury
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Sources
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mitochondria
endoplasmic reticulum
external to the cell
Consequences (activates enzymes)
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ATPase
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phospholipase
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endonuclease
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decreased ATP
decreased phospholipids
nuclear chromatin damage
Web Resources
Cell Membrane:
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http://arbl.cvmbs.colostate.edu/hbooks/molecules/sodium_p
ump.html
Kimbal’s Biology Page(s): You want it, he’s got it!:
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Web Resources
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Virtual Library of Cell Biology:
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On-line pathophysiology course:
http://www.d.umn.edu/~sdowning/Membranes/lecturenotes.
html#anchor360899
Sodium Potassium ATP pump:
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Thank you for attention
Increased Cytosolic Calcium
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Radiation
Inflammation
Oxygen toxicity
Chemicals
Reperfusion injury
http://www.ultranet.com/~jkimball/BiologyPages/T/TOC.html
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http://vl.bwh.harvard.edu/
http://sonser4.nur.uth.tmc.edu/patho/