General pathology lecture 1 introduction & cell injury

Dr. Barcarse

1. INTRODUCTION
and
CELL INJURY
Lecture 1

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. It is the “scientific study of disease“.
"scientific study of the molecular, cellular,
tissue, or organ system response to
injurious agents."
Definition of Pathology
Pathology serves as a Pathology serves as a "bridge""bridge" or or "link" "link" between the preclinical between the preclinical
ssciencesciences ( (anatomy, physiology, anatomy, physiology, …………etcetc.) and the courses in clinical .) and the courses in clinical
medicine.medicine.

5. What is the Disease?
•It is the “state in which an individual
exhibits an anatomical, physiological, or
biochemical deviation from the normal”.

6. In order for a subject or course to be
meaningful, one should become familiar
with the basic terminology applicable to
that subject!!!!!!
Basic Language of Pathology

7. •General Pathology
–Common changes in all tissues. e.g..
Inflammation, cancer, ageing, edema,
hemorrhage ….etc.
•Systemic Pathology
–Discussing the pathologic mechanisms in
relation to various organ systems e.g. CVS,
CNS, GIT…..etc.
Learning Pathology:

8. •Definition.
•Epidemiology – Where & When.
•Etiology – What is the cause?
•Pathogenesis - Evolution of dis.
•Morphology - Structural Changes
•Functional consequences
•Management
•Prognosis
•Prevention
Pathology
What should we know about a Disease?

9. Pathology focuses on 4 aspects of
disease:

ETIOLOGY:ETIOLOGY: CauseCause of disease. of disease.

PATHOGENESIS:PATHOGENESIS:
MechanismsMechanisms of development of disease. of development of disease.

MORPHOLOGY:MORPHOLOGY:
The The structural alterationsstructural alterations induced in cell and tissues. induced in cell and tissues.

FUNCTIONAL CONSEQUENCES:FUNCTIONAL CONSEQUENCES:
Functional results of the morphologic changes, as observed Functional results of the morphologic changes, as observed
clinicallyclinically..

10. Manifestations of Diseases
The manifestations of a disease are the sum of
the damage done by a harmful agent and the
body’s response.
The variation in these components accounts for
the great diversity of disease, which can be
classified into 4 main groups:
1. Developmental – genetic, congenital
2. Inflammatory - trauma, infection, immune
3. Neoplastic - tumors, cancers
4. Degenerative – ageing
5. Iatrogenic – drug-induced

11. Manifestations of Diseases
•Signs – are objective findings as perceived by an examiner,
physician or dentist
•Symptoms – are functional manifestations or evidences of a
disease process
•Lesions – 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 – a sudden increase in the severity or seriousness
of the signs and symptoms during the course of a disease.
•Remissions – become less intense at a time.
•Complications – unfavorable conditions that arise during the
course of a disease
•Sequelae – 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 – radiation, trauma or mechanical injury, thermal
changes, electrical, nuclear or X-rays, changes in
atmospheric pressure
- CHEMICAL AGENTS – 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. •
One etiologic One etiologic
agent several agent several
diseases, as diseases, as
smoking.smoking.
Disease
•
Several etiologic agents Several etiologic agents
one disease, as one disease, as
diabetes .diabetes .
Disease
Disease
Disease
Disease

One etiologic agent One etiologic agent

- one disease, as - one disease, as
MalariaMalaria..
Etiology

14. Environmental agents:
•Physical
•Chemical
•Nutritional
•Infections
•Immunological
•Psychological
Genetic Factors:
•Age
•Genes
Multifactorial::
As Diabetes, As Diabetes,
HypertensionHypertension
CancerCancer
Etiology:
What is the cause?

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,”from the time it is initiated to its final
conclusion in recovery or death”
The core of the science of pathology — The core of the science of pathology —
the study the the study the
pathogenesis of the disease.pathogenesis of the disease.

16. METHODS OF STUDYING
PATHOLOGY
•GROSS EXAMINATION
•LIGHT MICROSCOPY
•IMMUNOCHEMISTRY
•ELECTRON MICROSCOPY
•MOLECULAR BIOLOGY

17. 
Necropsy: Gross examination of the animal
cadaver by systematic dissection in order to
evaluate any abnormal changes (lesions) that
may be present.

Autopsy: Synonymous to necropsy in human
medicine

Biopsy: Removal and examination of tissue
obtained from the living body

Euthanasia: Intentional putting to death of an
individual with an incurable or painful disease by
employing humane means

18. Types of Diseases
•Acute – characterized by a sudden onset or in a rapid
course
•Fulminating – an acute fatal disease
•Chronic – slow onset and long duration or having a long
course
•Intercurrent – occurs during the course of another
disease
•Idiopathic – disease with unknown cause
•Teratogenic – diseases that are cause by drugs that
cross the placental barrier and harm the fetus
•Contagious – transmitted by direct, intimate or by skin
contact
•Venereal – transmitted by sexual contact
•Infectious – are caused by pathogenic microorganisms
•Communicable – 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.

20. CELL INJURY

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

22. Adapted
Cell
+ Stress
Injury
Normal
cell
Reversibly
injured cell
Irreversibly
Injured cell
Dead cell
+Stress
Apoptosis
Necrosis
- Stress
- Stress
Overview

23. The Normal Cell

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

25. Ischemic Injury

26. Mechanisms of Cell
Injury
Ischemic injury

27. Cell injury and death
•Reversible hypoxic/ ischemic injury
Loss of ATP generation by mitochondria initially
results in reversible events:
oNa+/K+ ATPase membrane pump leads to a loss of
ionic and osmotic gradient ( ↑edCa+2+ Na+, ↓ed K+
and osmotic gain of water) resulting cell swelling & ER
dilatation)
o↑ed anaerobic glycolysis results in glycogen depletion
and lactate accumulation (↓ed pH).
oReduced protein synthesis due to ribosome
detachment from the RER

28. Morphology of Cell Injury
and Necrosis
•Cell Injury – Reversible
– Irreversible
•Cell Death – Necrosis
– Apoptosis

29. Cell Injury and Death
•Reversible Injury
oCell swelling develops when cells are incapable of
fluid an ion homeostasis (↓ed function of ATP
dependant pumps).
oFatty change the accumulation of lipid vacuoles in the
cytoplasm.
•Irreversible injury (Necrosis)
oTwo basic processes underlie the morphologic
changes of necrosis
Denaturation of protein
Enzymatic digestion of cell components

31. Morphology of Cell Injury
•Plasma membrane alteration
•Mitochondrial Changes
•Dilation of Endoplasmic reticulum
•Nuclear Alteration
Reversible Injury
Cellular swelling
Fatty change

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
•↑edCa+2 activates
omembrane phospholipases with resulting membrane damage
oIntracellular 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
•↑Ca+2 activates
omembrane phospholipases with resulting membrane
damage
oIntracellular proteases leading to cytoskeletal
degradation
•Phospholipid degradation products that accumulate are
directly toxic to the cell

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 C
2 H
5OH, chloroform, CCl
4,
during sever infections, in prolonged
anemia and in toxemia of pregnancy.
•Fatty liver is due to:
inability of the liver to synthesize
phospholipids
decreased lipoprotein release from
hepatocytes
Increased triglyceride production

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.

47. FATTY DEGENERATION
(Wallerian degeneration)

48. Hyaline Degeneration-Liver

49. HYALINE DEGENERATION

50. HYALINE DEGENERATION
•Zenker’s waxy hyaline masses - typhoid
fever; Weil’s disease or leptospirosis
•Mallory bodies- nutritional cirrhosis
•Russel bodies- chronic inflammation
•Crooke’s hyaline bodies - Cushing’s
syndrome
•Councilman bodies - yellow fever;
viral hepatitis

51. CUSHING’S SYNDROME
Crooke’s Hyaline bodies-Liver

52. LEPTOSPIROSIS
Zenker’s waxy hyaline masses-liver
Causative agent: Liptospira icterohaemorrhagica

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

54. LIPOIDAL DEGENERATION-
AORTA

55. LIPOIDAL DEGENERATION
(Cholesterol clefts)

56. •Next Meeting:
•Quiz on Normal Cell & Cell Injury
•Assignment: Intracellular Accumulations

57. “True 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!”
Author Unknown