Pathology is the study of disease through scientific methods. This document discusses several core concepts in pathology including cellular adaptations, injury, and death. It describes different types of cellular changes like hyperplasia, hypertrophy, atrophy, and metaplasia that can occur as adaptive responses to stressors. The document also examines the morphology and mechanisms of the two main types of cell death: necrosis and apoptosis. Necrosis is unprogrammed cell death due to external factors, while apoptosis is a tightly regulated genetic program of cell suicide.

1. Introduction to pathology
Dr. Jebessa Gemechu (MD, Assistant professor of pathology)

2. Introduction to pathology
Learning Objectives
• Upon completing this topic students should be able to:
1. Define pathology
2. Discuss the core aspects of disease in pathology
3. Know the diagnostic techniques used in pathology
4. Know the various categories of the causes of diseases
5. Know the course, outcome, consequences of diseases

3. The core aspects of diseases in
pathology
 Pathology is the study of disease by scientific
methods.
 The word pathology came from the Latin words
“patho” & “logy”.
 ‘Patho’ means disease and ‘logy’ means study.
 Diseases may, in turn, be defined as an abnormal
variation in structure or function of any part of the
body.

4. …..
Pathology gives explanations of a disease by studying
the following four aspects of the disease.
1. Etiology,
2. Pathogenesis,
3. Morphologic changes and
4. Functional derangements and clinical significance.

5. Cellular Adaptations, Cell Injury
and Cell death

6. Cellular response
- The normal cell is confined to a fairly normal
range of function & structure.
- It is nevertheless able to handle normal
physiologic demands, maintaining steady state
called homeostasis.
- More severe physiologic stresses & some
pathologic stimuli may bring about a number
of physiologic & morphologic cellular
adaptation.

7. …
• If the limits of adaptive response to a stimulus
are exceeded, or the cell is exposed to an
injurious agent or stress , a sequence of events
follows that is termed Cell injury.

9. Cellular adaptation
 It is a new but altered steady state which preserves the
viability of the cell & modulates its function as it
responds to a stimuli.
 Adaptations are reversible functional and structural
responses to changes in physiologic states E.g.
pregnancy and
 Some pathologic stimuli, during which new but altered
steady states are achieved, allowing the cell to survive
and continue to function

10. A. Hyperplasia
 It is an increase in number of cells in an organ or
tissue
 Usually resulting in increased volume of the organ
or tissue
 Hyperplasia takes place if the cellular population
is capable of synthesizing DNA or able to undergo
mitotic division
 Usually, it occurs together with hypertrophy
 It can be physiologic or pathologic

11. 1. Physiologic Hyperplasia
1. Due to the action of hormonal hyperplasia or
growth factor which increases the functional
capacity of a tissue when needed.
Eg. Proliferation of glandular epithelium of
female breast during pregnancy & puberty or
physiologic hyperplasia that occurs in
pregnant uterus.

12. 2. Pathologic hyperplasia
- Most are caused by excessive hormonal
stimulation or growth factors acting on target
cells
- Eg. Endometrial hyperplasia (due to estrogen),
benign prostatic hyperplasia (due to androgen)
Mechanisms of Hyperplasia -Hyperplasia is the
result of growth factor-driven proliferation of
mature cells and, in some cases, by increased
output of new cells from tissue stem cells.

13. Uterus

14. prostate

15. B. Hypertrophy
 It refers to an increase in the size of cells ,
 Resulting in an increase in the size of the organ.
 The increase in size is due to synthesis of more structural
components
 It can be physiologic or pathologic & is caused by
increased functional demand or by specific hormonal
stimulation
Example:
 The enlargement of the left ventricle in hypertensive
heart disease &
 The increase in skeletal muscle during strenuous
exercise

16. • Mechanisms of Hypertrophy -Hypertrophy is
the result of increased production of cellular
proteins.
• Much of our understanding of hyper trophy is
based on studies of the heart.
• There is great interest in defining the
molecular basis of hypertrophy since beyond a
certain point,

17. Figure –Physiologic hypertrophy of the uterus during pregnancy

18. Heart

19. C. Atrophy
 Shrinkage in the size of the cell by loss of cell
substance.
 Atrophy is defined as a reduction in the size of an
organ or tissue due to a decrease in cell size and
number.
 Atrophy can be physiologic or pathologic
Physiologic atrophy is common during early
development
 Early embryonic structures such as thyroglossal duct
undergo atrophy during fetal development.
 Uterus decreases in size shortly after parturition.

20. Pathologic atrophy
 It Can be local or generalized
The common causes of atrophy are the following
Decreased work load (Atrophy of disuse)
Loss of innervations (denervation atrophy)
Diminished blood supply
Inadequate nutrition
Loss of endocrine stimulation
Aging
Pressure
Mechanisms of Atrophy -Atrophy results from decreased
protein synthesis and increased protein degradation in
cells.
 Protein synthesis decreases because of reduced metabolic

21. Figure Atrophy. A, Normal brain of a young adult.
B, Atrophy of the brain in CVA

22. Brain…

23. D. Metaplasia
 It is a reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by another adult
cell type.
 It may represent an adaptive substitution of cells that are
sensitive to stress by cell types better able to withstand
the adverse environment
 Change inphenotype of differentiated cells,
often in response to chronic irritation, that makes cells
better able to withstand the stress; usually induced by
altered differentiation pathway of tissue stem cells; may
result in reduced functions or increased propensity for
malignant transformation

24. Metaplasia….
 The most common metaplasia is columnar to
squamous, as occurs in the respiratory tract in
response to chronic irritation
 The normal ciliated columnar epithelial cells of the
trachea & bronchi are often replaced focally or
widely by stratified squamous epithelial cells in
cigarette smokers
 The influences that predispose to metaplasia , if
persistent, may induce malignant transformation in
metaplastic epithelium

26. Metaplasia….
 Metaplasia from squamous to columnar type (Barret
esophagus) may also occur.
 Esophageal squamous epithelium is replaced by
intestinal - like columnar under the influence of
refluxed gastric acid
 Cancers may arise that are typically glandular
carcinoma (adenocarcinoma)

27. Mechanisms of Metaplasia - Metaplasia does
not result from a change in the phenotype of an
already differentiated cell type; instead it is the
result of a reprogramming of stem cells that
are known to exist in normal tissues, or of
undifferentiated mesenchymal cells present in
connective tissue.

28. Figure Metaplasia of columnar to squamous epithelium. A, Schematic
diagram.
B, Metaplasia of columnar epithelium (left) to squamous epithelium
(right) in a bronchus.

29. Cell Injury
 Cell injury results when cells are stressed so severely
that they no longer able to adapt or the cells are exposed
to inherently damaging agents .
 If the limits of adaptive responses are exceeded or if
cells are exposed to injurious agents or stress, deprived
of essential nutrients, or become compromised by
mutations that affect essential cellular constituents, a
sequence of events follows that is termed cell injury

30.  These alterations may be divided into the
following stages
 Reversible cell injury – is manifested as
functional & morphologic changes that are
reversible if the damaging stimulus is removed
 In early stages or mild forms of injury.
 The hallmarks of reversible injury are reduced
oxidative phosphorylation with resultant
depletion of energy (ATP)

31. • Irreversible injury or cell death – with
continuing damage , the injury becomes
irreversible at which time the cell cannot
recover and it dies.
• Historically, two principal types of cell death,
necrosis and apoptosis, which differ in their
morphology, mechanisms, and roles in
physiology and disease, have been recognized.

32. Causes of cell injury
 Oxygen deprivation- Hypoxia is a deficiency of oxygen ,
which causes cell injury by reducing aerobic oxidative
respiration.
 It should be distinguished from ischemia , which is loss of
blood supply from impeded arterial flow or reduced
venous drainage in tissue .
 Causes of hypoxia include cardio respiratory failure,
anemia, carbon monoxide poisoning
 Physical agents – mechanical trauma, extremes of
temperature, sudden changes in atmospheric pressure
 Chemical agents & Drugs
 Infectious agents
 Immunologic reactions
 Genetic derangements
 Nutritional imbalance

33. Mechanisms of cell injury
Principles that are relevant to most forms of cell
injury:-
 The cellular response to injurious stimuli
depends on the type of injury, its duration & its
severity
 The consequences of cell injury depend on the
type, state, & adaptability of the injured cell

34. Morphology of cell injury &
Necrosis
Reversible injury
Two patterns of reversible cell injury can be
recognized under the light microscope
1. Cell swelling
 The is the first manifestation of almost all
forms of injury to cell injury
 It appears whenever the cells are incapable of
maintaining ionic & fluid homeostasis & is
result of loss of function of plasma membrane
energy-dependent ion pumps.

35. Reversible injury….
2. Fatty change
- It is manifested by the appearance of small &
large lipid vacuoles in the cytoplasm & occurs
in hypoxic & various toxic injury.
- It is principally seen in cells involved in &
dependent on fat metabolism such as
hepatocytes & myocardial cell

36. Irreversible injury
Also called cell death
- Necrosis
- Apoptosis

37. A. Necrosis
- It refers to a spectrum of morphologic changes that
follow cell death in a living tissue resulting from the
progressive degradative action of enzymes in lethally
injured cells.
- Necrosis is cell death occurring in the setting of
irreversible exogenous injury.
- Necrotic cells aren’t able to maintain membrane
integrity & their content leak out & elicit
inflammation in the surrounding tissue

38. Morphology of necrosis
- The morphologic features of necrosis is the
result of denaturation of intracellular proteins &
enzymatic digestion of the lethargic injury cell.
- These processes require hrs to develop so there
would be no detectable change immediately.

39. Morphology…
Necrotic cells show increased eosinophilia due to
loss the normal basophilia imparted by RNA in
the cytoplasm
1. Nuclear changes-appear in one of three
patterns, all due to nonspecific breakdown of
DNA
A. Karyolysis – The basophilia of the nucleus fades
B. Pyknosis- Nuclear shrinkage & increased basophilia
C. Karyorrhexis – Nuclear fragmentation

41. 2. Morphologic patterns of necrosis
A. Coagulative necrosis
 Most often results from sudden interruption of
blood supply to an organ.
 It is, in early stages, characterized by g
preservation of tissue architecture when
denaturation is the primary pattern
 Is a form of necrosis in which the architecture
of dead tissues is preserved for a span of at
least some days

42. Figure- Coagulative necrosis.
A, a wedge-shaped kidney infarct (yellow).

43. B. Microscopic view of the edge of the infarct, with normal
kidney

44. B. Liquefactive necrosis
 It is characterized by digestion of tissue.
 It shows softening & liquefaction of tissue.
 Characteristically results from ischemic injury
to the CNS.
 Also occurs in suppurative infections
characterized by formation of pus.
 Is contrast to Coagulative necrosis, is
characterized by digestion of the dead cells,

45. Figure - Liquefactive necrosis. An infarct in the brain,
showing dissolution of the tissue.

48. C. Gangrenous necrosis
 It is due to vascular occlusion & most affects the lower
extremities & the bowel.
 Is not a specific pattern of cell death, but the term is
commonly used in clinical practice.
 When there is more Liquefactive necrosis because of the
actions of degradative enzymes in the bacteria and the
attracted leukocytes (giving rise to so-called wet
gangrene).

50. D. Caseous necrosis
 It is type of necrosis most often seen in foci of
tuberculosis infection.
 The term Caseous is derived from the cheesy
white gross appearance of the area of necrosis
 On microscopic examination, the necrotic
focus appears as amorphous granular debris
enclosed within a distinctive inflammatory
border known as a granulomatous reaction

51. Figure-Caseous necrosis. Tuberculosis of the lung, with a large
area of Caseous necrosis containing yellow-white & cheesy
debris.

53. E. Fat necrosis
 Focal areas of fat destruction, typically
occurring as a result of release of activated
pancreatic lipases into the substance of the
pancreas & the peritoneal cavity. This occurs
in acute pancreatitis.
 The activated enzymes liquefy fat cell
membranes & the lipases split the triglyceride
contained with in fat cells.
 Does not in reality denote a specific pattern of
necrosis.

55. Fat necrosis.

57.  Necrosis can be followed by release of
intracellular enzymes into the blood (
creatinine kinase or troponin in myocardial
infarction ), inflammation or dystrophic
calcification ( if necrotic cells are not
phagocytosed.
 They tend to attract calcium salts )

58. F. Fibrinoid necrosis????
 Is a special form of necrosis usually seen in
immune reactions involving blood vessels.
 This pattern of necrosis typically occurs
when complexes of antigens and antibodies
are deposited in the walls of arteries

59. B. Apoptosis
 It is a pathway of cell death that is induced by tightly
regulated intracellular program in which cells destined to
die activate enzymes that degrade the cells’ own nuclear
DNA & nuclear & cytoplasmic proteins.
 Apoptotic cells break up into fragments, called apoptotic
bodies Apoptosis is sometimes referred to as
programmed cell death. , as certain forms of necrosis,
called necroptosis, are also genetically programmed, but
by a distinct set of genes

60. Causes of Apoptosis
• Apoptosis occurs normally both during
development and throughout adulthood, and
serves to remove unwanted, aged, or
potentially harmful cells.
• It is also a pathologic event when diseased
cells become damaged beyond repair and are
eliminated

61. Apoptosis in physiologic situations
The following important in the physiologic
situations:
 Programmed destruction of cells during
embryogenesis, Death of host cells, Cell loss in
proliferating cell population, Elimination of
potentially harmful self-reactive lymphocytes
 Hormone –dependent involution in the adult such as
endometrial cell breakdown during menstrual cycle ,
the regression of the lactating breast after weaning.
Is death by apoptosis is a normal phenomenon that
serves to eliminate cells that are no longer needed,
and to maintain a steady number of various cell
populations in tissues.

62. Apoptosis in Pathologic conditions
Apoptosis eliminates cells that are injured beyond
repair without eliciting a host reaction, thus limiting
collateral tissue damage.
Death by apoptosis is responsible for loss of cells in a
variety of pathologic states:-
 Cell death produced by a variety of injurious stimuli
such as radiation & cytotoxic anticancer drugs
 Cell injury in certain viral diseases such as viral
hepatitis
 Pathologic atrophy in parenchymal organs after duct
obstruction, such as occurs in the pancreas, parotid
gland, and kidney.
 Cell death in tumors. Accumulation of misfolded
protein.

63. Morphology
The following morphologic features characterize cells
undergoing apoptosis
 Cell shrinkage- The cell is smaller in size, the cytoplasm
is dense and the organelles, although relatively normal.
 Chromatin condensation-This is the most characteristic
feature of apoptosis.
 Formation of cytoplasmic blebs & apoptotic bodies-The
apoptotic cell undergoes fragmentation into membrane
bound apoptotic bodies
 Phagocytosis of apoptotic cells or cell bodies usually by
macrophages

64. Summery

65. Features of Necrosis and Apoptosis
Feature Necrosis Apoptosis
Cell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis, karyorrhexis,
karyolysis
Fragmentation into
nucleosome size fragments
Plasma membrane Disrupted Intact; altered structure,
especially orientation of
lipids
Cellular contents Enzymatic digestion; may
leak out of cell
Intact; may be released in
apoptotic bodies
Adjacent inflammation Frequent No
Physiologic or pathologic
role
Invariably pathologic
(culmination of irreversible
cell injury)
Often physiologic, means of
eliminating unwanted cells;
may be pathologic
after some forms of cell
injury, especially DNA
damage