2. Medicine, to produce health
must study disease
And music, to produce harmony
must study discord.
by Plutarch
3. Introduction
⢠PATHOLOGY IS THE STUDY OF DISEASE.
⢠IT DESCRIBES THE MANIFESTATIONS OF
THE DISEASE, ITS PROCESS AND
SEQUELAE AND ATTEMPTS TO DETERMINE
THE CAUSE (ETIOLOGY) AND UNDERLYING
MECHANISM (PATHOGENESIS).
⢠IT FORMS A BRIDGE BETWEEN BASIC
SCIENCE AND CLINICAL PRACTICE.
4. Definition of Pathology
It is the âscientific study of diseaseâ.
"scientific study of the molecular, cellular,
tissue, or organ system response to
injurious agents."
Pathology serves as a "bridge" or "link" between the preclinical
sciences (anatomy, physiology, âŚâŚetc.) and the courses in clinical
5. What is the Disease?
⢠It is the âstate in which an individual
exhibits an anatomical, physiological, or
biochemical deviation from the normalâ.
6. Basic Language of Pathology
In order for a subject or course to be
meaningful, one should become familiar
with the basic terminology applicable to
7. Learning Pathology:
⢠General Pathology
â Common changes in all tissues. e.g..
Inflammation, cancer, ageing, edema,
hemorrhage âŚ.etc.
⢠Systemic Pathology
â Discussing the pathologic mechanisms in
relation to various organ systems e.g. CVS,
CNS, GITâŚ..etc.
8. What should we know about a Disease?
⢠Definition.
⢠Epidemiology â Where & When.
⢠Etiology â What is the cause?
gy
⢠Pathogenesis - Evolution of dis. th o
lo
Pa
⢠Morphology - Structural Changes
⢠Functional consequences
⢠Management
⢠Prognosis
⢠Prevention
9. Pathology focuses on 4 aspects of
disease:
ďŹ ETIOLOGY: Cause of disease.
ďŹ PATHOGENESIS:
Mechanisms of development of disease.
ďŹ MORPHOLOGY:
The structural alterations induced in cell and tissues.
ďŹ
10. Manifestations of Diseases
The manifestations of a disease are the sum of
the damage done by a harmful agent and the
bodyâs response.
The variation in these components accounts for
the great diversity of disease, which can be
classified into 4 main groups:
1. Developmental â genetic, congenital
2. Inflammatory - trauma, infection, immune
3. Neoplastic - tumors, cancers
4. Degenerative â ageing
5. Iatrogenic â drug-induced
11. Manifestations of Diseases
⢠Signs â are objective findings as perceived by an examiner,
physician or dentist
⢠Symptoms â are functional manifestations or evidences of a
disease process
⢠Lesions â are visible changes produced by a disease in the tissues
or organs. They are usually local abnormalities which could be
benign, cancerous, gross, occult, or primary.
⢠Exacerbations â a sudden increase in the severity or seriousness
of the signs and symptoms during the course of a disease.
⢠Remissions â become less intense at a time.
⢠Complications â unfavorable conditions that arise during the
course of a disease
⢠Sequelae â are remote aftereffects produced by a disease.
12. ETIOLOGY
Knowledge or discovery of the primary etiology remains the backbone on which a
diagnosis can be made and a disease process can be best understood so that a
treatment can be prescribed.
THE ETIOLOGICAL FACTORS ARE:
- ENVIRONMENTAL FACTORS
- GENETIC FACTORS
- IINDIRECT CAUSES
ENVIRONMENTAL FACTORS ARE:
- PHYSICAL AGENTS â radiation, trauma or mechanical injury, thermal
changes, electrical, nuclear or X-rays, changes in
atmospheric pressure
- CHEMICAL AGENTS â chemicals, poisons like venoms or toxins,
corrosive agents like strong acids and alkalis
-NUTRITIONAL DEFICIENCES AND EXCESSES
- INFECTIONS AND INFESTATIONS
- ABNORMAL IMMUNOLOGICAL REACTIONS
- PSYCHOLOGICAL FACTORS
GENETIC FACTORS: ABNORMAL GENES
INDIRECT CAUSES: pertain to the predisposing factors like age, age, sex,
environment, race, climate, state of nutrition, habits
13. Etiology
Disease Disease
Disease
Disease
Disease
ďŹOne etiologic agent
â˘One etiologic
- one disease, as â˘Several etiologic agents agent several
Malaria.
one disease, as diseases, as
diabetes . smoking.
14. Etiology:
What is the cause?
ď Environmental agents:
⢠Physical
⢠Chemical
⢠Nutritional
Multifactorial:
⢠Infections
As Diabetes,
⢠Immunological
⢠Psychological Hypertension
ď Genetic Factors: Cancer
⢠Age
⢠Genes
15. Pathogenesis
The sequence events in the response of the
cells or tissues to the etiologic agent, from the
initial stimulus to the ultimate expression of the
disease,âfrom the time it is initiated to its final
conclusion in recovery or deathâ
The core of the science of pathology â
the study the
16. METHODS OF STUDYING
PATHOLOGY
⢠GROSS EXAMINATION
⢠LIGHT MICROSCOPY
⢠IMMUNOCHEMISTRY
⢠ELECTRON MICROSCOPY
⢠MOLECULAR BIOLOGY
17. ďŹNecropsy: Gross examination of the animal
cadaver by systematic dissection in order to
evaluate any abnormal changes (lesions) that
may be present.
ďŹAutopsy: Synonymous to necropsy in human
medicine
ďŹBiopsy: Removal and examination of tissue
18. Types of Diseases
⢠Acute â characterized by a sudden onset or in a rapid
course
⢠Fulminating â an acute fatal disease
⢠Chronic â slow onset and long duration or having a long
course
⢠Intercurrent â occurs during the course of another
disease
⢠Idiopathic â disease with unknown cause
⢠Teratogenic â diseases that are cause by drugs that
cross the placental barrier and harm the fetus
⢠Contagious â transmitted by direct, intimate or by skin
contact
⢠Venereal â transmitted by sexual contact
⢠Infectious â are caused by pathogenic microorganisms
⢠Communicable â are transmitted by agents, fomites,
vector or carrier
19. Prognosis
Expected outcome of the
disease; it is the clinician's
estimate of the severity and
possible result/s of a disease.
21. What is cell injury?
⢠Cell injury is a sequence of events that
occur if the limits of adaptive capability are
exceeded or no adaptive response is
possible.
⢠Most common causes are: ischemia,
hypoxia, chemical injury, and injury
produced by infectious agents
24. Mechanisms of Cell Injury
⢠Depletion of ATP
⢠Mitochondrial Damage
⢠Influx of Intracellular Calcium and Loss
of Calcium Homeostasis
⢠Accumulation of Oxygen-Derived free
radical (Oxidative stress)
⢠Defects in Membrane Permeability
27. Cell injury and death
⢠Reversible hypoxic/ ischemic injury
Loss of ATP generation by mitochondria initially
results in reversible events:
o Na+/K+ ATPase membrane pump leads to a loss of
ionic and osmotic gradient ( âedCa+2+ Na+, âed K+
and osmotic gain of water) resulting cell swelling & ER
dilatation)
o âed anaerobic glycolysis results in glycogen depletion
and lactate accumulation (âed pH).
o Reduced protein synthesis due to ribosome
detachment from the RER
28. Morphology of Cell Injury
and Necrosis
⢠Cell Injury â Reversible
â Irreversible
⢠Cell Death â Necrosis
â Apoptosis
29. Cell Injury and Death
⢠Reversible Injury
o Cell swelling develops when cells are incapable of
fluid an ion homeostasis (âed function of ATP
dependant pumps).
o Fatty change the accumulation of lipid vacuoles in the
cytoplasm.
⢠Irreversible injury (Necrosis)
o Two basic processes underlie the morphologic
changes of necrosis
ď§ Denaturation of protein
ď§ Enzymatic digestion of cell components
32. Morphology of Cell Injury
Ultrastructural Changes:
⢠Alteration in plasma membrane reflecting
disturbance in ion and volume regulation
induced by loss of ATP
⢠Mitochondrial changes
⢠Endoplasmic reticulum changes
⢠Changes in the lysosomes
33. Alteration in the Plasma Membrane
⢠Cellular swelling
⢠Formation of
cytoplasmic blebs
⢠Blunting and
distortion of microvilli
⢠Creation of myelin
figures
⢠Deterioration and
loosening of
intercellular
attachments
34. Mitochondrial Changes
⢠Early, appears
condensed as a result
of loss of matrix protein
following loss of ATP
⢠Followed by swelling
due to ionic shifts
⢠Amorphous densities
which correlate with the
onset of irreversibility
⢠Finally, rupture of
membrane followed by
progressing increased
calcification
35. Endoplasmic reticulum changes
⢠Dilatation
⢠Detachment of
ribosomes and
disaggregation of
polysomes with
decreased protein
synthesis
⢠Progressive
fragmentation
and formation of
intracellular
aggregates of
myelin figures
36. Changes in the Lysosomes
⢠Generally appear
late
⢠Swelling
rupture
disappear
⢠some fused with
the autohagic
vacuoles
(phagosomes)
which become
apparent within
damaged cells
37. Cell Injury and Death
Irreversible hypoxic/ ischemic injury
⢠These changes are reversible if O2 and flow are reinstated, the
transition to irreversible injury depends on the extent of ATP
depletion and membrane dysfunction especially of mitochondria.
⢠ATP depletion results in MPT with loss of the H+ gradient
⢠ATP depletion releases cytochrome c that can induce apoptosis
⢠âedCa+2 activates
o membrane phospholipases with resulting membrane damage
o Intracellular proteases leading to cytoskeletal degradation
⢠Phospholipid degradation products that accumulate are directly
toxic to the cell
38. Cell Injury and Death
Irreversible hypoxic/ ischemic injury
⢠These changes are reversible if O2 and flow are
reinstated, the transition to irreversible injury depends on
the extent of ATP depletion and membrane dysfunction
especially of mitochondria.
⢠ATP depletion results with loss of the H+ gradient
⢠ATP depletion releases cytochrome c that can induce
apoptosis
⢠âCa+2 activates
o membrane phospholipases with resulting membrane
damage
o Intracellular proteases leading to cytoskeletal
degradation
⢠Phospholipid degradation products that accumulate are
directly toxic to the cell
39.
40. Types of Cell Injury
2.Cloudy or cellular swelling or
parenchymatous degeneration
3.Hydrophic swelling
4.Fatty change
5.Hyaline degeneration
6.Lipoidal degeneration
7.Mucoid or mucinous degeneration
41. ⢠Cloudy swelling is
due to failure of the
cellular sodium
pump. This allows
excess Na+ to enter
cells and eventually
increases cellular
water.
⢠Hydropic
degeneration is a
severe form of
cloudy swelling. It
occurs with
hypokalemia due to
vomiting or diarrhea.
42. Fatty Degeneration
⢠Fatty degeneration or fatty
metamorphosis, steatosis is the
abnormal appearance of fat within
parenchymal cells.
⢠It results from hepatotoxic agents
such as C2 H5OH, chloroform, CCl4,
during sever infections, in prolonged
anemia and in toxemia of pregnancy.
⢠Fatty liver is due to:
ď inability of the liver to synthesize
phospholipids
ď decreased lipoprotein release from
hepatocytes
ď Increased triglyceride production
43.
44. ⢠Hydropic change or Vacuolar
degereration.
⢠Appears whenever cells are incapable of
maintaining ionic and fluid homeostasis.
⢠The first manifestation of almost all forms
of cell injury.
⢠Reversible injury.
Gross Findings
⢠Pallor, increased turgor, and increased in
weight.
45. Micro Findings
⢠1. Cell swelling, cytoplasm contains coarse
granules.
⢠2. Nucleus not affected in light microscopy..
⢠3. Pigmented cast, hyaline cast.
D. Others:
⢠1. The first manifestation of cell injury and is
reversible.
⢠2. Increasing hydration of the cell due to
alteration in ion transport at cell membrane.
⢠3. Cause: infection, physico-chemical injury
( toxic ), ischemia
46. FATTY PHANEROSIS-LIVER
⢠Fatty
phanerosis is
the
unmasking of
invisible fat.
⢠Lipid
accumulates
in the liver
cells, mainly
in the form of
triglycerides.
53. Mucinous Degeneration-Colon
⢠When there is
excessive amount
of mucous in
unusual location,
it is called
mucous deg.
⢠Cancer with high
degree of mucous
deg are called
mucinous
carcinoma or the
colloid carcinoma.
⢠Two types of
mucin: true mucin
and paramucin
56. ⢠Next Meeting:
⢠Quiz on Normal Cell & Cell Injury
⢠Assignment: Intracellular Accumulations
57. âTrue wisdom is in leaning
On Jesus Christ our Lord
True wisdom is in trusting
His own life-giving Word,
True wisdom is in living
Near Jesus everyday
True wisdom is in walking
Where He shall lead the way!â
Author Unknown
Hinweis der Redaktion
Normal cell has relative narrow range of functions and structure Limited changes in metabolism = homeostasis (increased Glc and TG metabolism in active contracting muscle) Stress = demands in excess of normal homeostatic changes leads to adaptations If stress exceeds adaptive response of cell -ď injury In addition, a variety of agents can directly injure cells (ie CN, , Hg, pH, temp, etc)