Anatomy

1. Introduction To Pathology
By A.I

2. Pathology
2
• Greek (pathos -suffering, logos -study).
• A scientific study of disease
• Bridging discipline which encompasses both basic
science and clinical practice.

3. CONT…
• It is divided into
– General pathology
• cellular and tissue responses to pathologic
stimuli
– Systemic pathology
• responses of specialized organs pathologic
stimuli
3

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.
4

5. 1. Etiology - means the cause of the disease.
• Can be known (1ry) or unknown (idiopathic)
• primary cause is a back bone for the diagnosis
and treatment development
• Etiologic factors
– genetic/intrinsic
– Acquired
– multifactorial (Env’t & genetics)
5

6. 2. Pathogenesis – means mechanism for
development of the disease
• Sequence of events that leads to morphologic
changes.
6

7. 3. Morphologic changes –
• refer to the structural alterations in cells or
tissues that occur following the pathogenetic
mechanisms
• Can be gross or microscopic change
• The changes may be specific to a disease,
that help pathologist diagnose the disease
7

8. 4. Functional derangements and clinical features
• are consequences of morphologic changes
Out come and prognosis
– Cure/resolution
– Disability/permanent damage
– Death
8

9. • In summary, pathology studies:-
• Etiology  Pathogenesis  Morphologic
changes  Clinical features  outcome &
Prognosis of all disease
• Understanding of the above core aspects of
disease (i.e. understanding pathology) will
help one to understand how the clinical
features of different diseases occur & how
their treatments work
9

10. Diagnostic techniques used in pathology
• The pathologist uses the following techniques to
the diagnose diseases:
– Histopathology
– Cytopathology
– Hematopathology
– Immunohistochemistry
– Microbiological examination
– Biochemical examination
– Cytogenetics
– Molecular techniques
– Autopsy
10

11. A.Histopathological techniques
• studies tissues abnormalities under
microscope.
• The gold standard for pathologic diagnosis.
• Tissues obtained by biopsy.
• Biopsy
– a tissue sample from a living person to identify
the disease.
– can be either incisional or excisional.
11

12. 12

13. B. Cytopathologic methods
study of cells from various body sites to
determine the cause or nature of disease.
Advantages :
– it is cheap, takes less time and needs no
anesthesia to take specimens.
– it is complementary to histopathological
examination.
13

14. Cytopathologic methods includes:
1. Fine-needle aspiration cytology (FNAC)
– cells are obtained by aspirating the diseased organ
uses a very thin needle
– the aspirated cells are then stained and studied under
the microscope.
– Superficial organs (e.g. thyroid,breast, LNs, skin and
soft tissues)
• can be easily aspirated.
– Deep organs; such as the lung, liver, pancreas, kidney
• aspirated with guidance by fluoroscopy, ultrasound or CT
scan.
14

15. 15

16. 16

17. • 2. Exfoliative cytology
–examination of cells that are shed
spontaneously into body fluids or
secretions.
–Includes sputum, CSF, effusions in body
cavities (pleura, pericardium, peritoneum)
17

18. • 3. Abrasive cytology
– Refers to methods by which cells are dislodged by
various tools from body surfaces (skin, mucous
membranes, and serous membranes).
– E.g. Pap smears: preparation of cervical smears
with a spatula or a small brush to detect cancer of
the uterine cervix at early stages.
18

19. 19

20. • Applications of cytopathology:
– 1. Screening or early detection of asymptomatic
cancer.
– 2. Diagnosis of symptomatic cancer
– 3. To diagnose cysts, inflammatory conditions and
infections of organs
– 4. Surveillance of patients treated for cancer
• periodic urine cytology to monitor the
recurrence of cancer of the UT
20

21. • C. Hematological examination
– abnormalities of the cells of the blood and their
precursors in BM are investigated
– Used to diagnose different kinds of anemias & leukemias.
• D. Immunohistochemistry
– used to detect a specific antigen in the tissue in order to
identify the type of disease.
• E. Microbiological examination
– Identifying micro-organisms from body fluids,cells and
excised tissues
– Uses microscopy,cultural and serological techniques
21

22. • F. Biochemical examination
– Assessment of metabolic disturbances of disease
– Using assay of various normal and abnormal
compounds in the blood, urine, etc.
22

23. • G. Molecular techniques
– used to detect genetic diseases.
– The techniques such as fluorescent in situ
hybridization, Southern blot, PCR etc...
• H. Cytogenetics,
– Asses chromosomal abnormalities in the cells using
of molecular techniques
23

24. • I. Autopsy
– Examination of the dead body to identify the
cause of death.
– can be done for forensic or clinical purposes.
24

25. Cellular Responses to Stress and Noxious Stimuli
• Homeostasis
– it is the steady state that cells exist in
normally
–an equilibrium of cells with their
environment for adequate function
–disturbance of it leads to disease onset
25

26. 26

27. • Example: heart muscle
• Increased hemodynamic loads the heart
muscle becomes enlarged (adaptation) the
blood supply to the myocardium is
inadequate reversible injury  Eventually
irreversible injury and die
27

28. • Stresses may also induce the following
changes in cells and tissues
– intracellular accumulations,
– pathologic calcification, and
– Cell aging
28

29. CELLULAR ADAPTATIONS TO STRESS
• Adaptations
– reversible functional and structural responses
– a new but altered steady states is achieved
– allow the cell to survive and continue to function
during changes in physiologic states (e.g.,
pregnancy) and some pathologic stimuli
– It is a response by cells for physiologic stresses or
pathologic stimuli
29

30. • Physiologic adaptations
– responses of cells to normal stimulation by
hormones or endogenous chemical mediators
e.g., the hormone-induced enlargement of the
breast and uterus during pregnancy
• Pathologic adaptations
– responses to stress that allow cells to modulate
their structure and function and thus escape
injury
30

31. • Adaptation can be by:-
– Hypertrophy
– Atrophy
– Hyperplasia
– Metaplasia
31

32. Hypertrophy
• it is increase in cell size resulting in increase in
the size of the organ
• Cellular enlargment is due to increased
synthesis of cell structural components and
organelles leads to an increase in organ size and
function.
• Causes
a. increased functional demand
• b. specific hormonal stimulation
32

33. Physiologic hypertrophy
33

34. Pathological Hypertrophy
Pathologic hypertrophy
34

35. Hyperplasia
• it is an increase in the number of normal cells
that leads to an increase in the size of the
organ
35

36. • Hyperplasia can be physiologic or pathologic.
• physiologic hyperplasia includes
• (1) hormonal hyperplasia
– eg. Enlargment of female breast at puberty and during
pregnancy
• (2) compensatory hyperplasia
- a type of hyperplasia that occurs when a
portion of the tissue is removed or diseased
eg. Hepatocyte hyperplasia when a liver is resected
36

37. • pathologic hyperplasia are caused by excessive
hormonal or GF stimulation,
• Examples
1. in balance between estrogen and progesterone
 endometrial hyperplasia abnormal
menstrual bleeding
2.the growth factors may be produced by papilloma
viruses or by infected cell hyperplastic
epithelium  skin warts and mucosal lesions
• Pathologic hyperplasia , if untreated may
developed to cancer
eg. Endometrial hyperplasia to endometrial ca. 37

38. Regenerative capacity of cells
a. Labile cells (stem cells)
– divide continuously
– mainly undergo hyperplasia as an adaptation to injury
– e.g., stimulation of RBC stem cells by EPO in blood loss.
b. Stable cells (resting cells)
– divide infrequently
– undergo hyperplasia and/or hypertrophy
– Eg. hyperplasia of hepatocytes in liver injury;
• hyperplasia and hypertrophy of smooth muscle cells in the uterus
during pregnancy)
c. Permanent cells (non replicating cells)
– highly specialized cells
– undergo hypertrophy only
– e.g., cardiac and striated muscle
38

39. Atrophy
• Shrinkage in the size of the cell by the loss of
cell substance is known as atrophy.
• When a sufficient number of cells involved,
the entire tissue or organ diminishes in size,
becoming atrophic
• atrophic cells may have diminished function,
they are not dead.
39

40. 40

41. 41

42. • Causes :
• 1. disuse
• 2. denervation
• 3. diminished blood supply
• 4. loss of endocrine stimulation
– e.g., hypopituitarism causing atrophy of target
organs such as the thyroid
• 5. aging (senile atrophy).
42

43. • Cellular mechanisms of Atrophy
• 1. decreased protein synthesis because of
reduced metabolic activity
• 2. increased protein degradation due to
ubiquitin-proteasome pathway
• Nutrient deficiency and disuse  activate
ubiquitin ligases,  attach ubiquitin peptide
to cellular proteins proteasomes target
these proteins and degrade them
43

44. Metaplasia
• replacement of one fully differentiated cell
type by another
• cells sensitive to a particular stress are
replaced by other cell types better able to
withstand the adverse environment
• Metaplasia is thought to arise by genetic
"reprogramming" of stem cells rather than
transdifferentiation of already differentiated
cells.
44

45. • Types of metaplasia
• a. Squamous: replacement of columnar
epithelium by squamous epithelium e.g.,
squamous metaplasia of main stem bronchus
45

46. 46

47. • b. Glandular: replacement of squamous
epithelium with intestinal cells (goblet cells,
mucus secreting cells)
Eg . Barrett's esophagus
47

48. 48

49. • Advantage:
– Protective against inciting stimuli
• Disadvantage:
– Loss of functional capability of original cell type
– Risk of cancerous transformation
49

50. Cell injury
• Results when cells failed or unable to adapt to
stresses, injurious agents or intrinsic
abnormalities
• Injury may progress through a reversible stage
 become irreversible  culminate in cell
death
50

51. CAUSES OF CELL INJURY
A. Hypoxia: is decreased oxygen supply to tissues
• It can be caused by:
1. Ischemia which- is a decreased blood flow
-- the most common cause
2. Anemia- a reduction in the number of oxygen
carrying RBCs
3. Carbon monoxide poisoning - decreases the
oxygen-capacity of RBCs by chemical alteration of
hemoglobin
4. pulmonary disease - Poor oxygenation of blood
51

52. B. Chemical Agents
includes: - Excess of innocuous substances
- poisons
- potentially toxic agents
- therapeutic drugs
• Mechanisms -- by altering membrane
permeability, osmotic homeostasis, or the
integrity of an enzyme or cofactor
52

53. C. Infectious Agents
- range from submicroscopic viruses to meter-
long tapeworms
D.Immunologic Reactions
- Examples include autoimmune reactions and
allergic reactions against environmental
substances in genetically susceptible
individuals
53

54. E. Genetic Defects
- leads to cell injury by resulting deficiency of
functional protein
- It can result in gross pathologic changes
(eg.Down syndrome ) or microscopic( eg.sickle
cell anemia)
54

55. .
F. Nutritional Imbalances
- deficiencies or excesses
G . Physical Agents
- Trauma, extremes of temperatures,
radiation, electric shock …
H. Aging
- Cellular senescence decreased replicative
and repair abilities of individual cells and
tissues diminished ability to respond to
damage the death of cells and of the
organism 55

56. MECHANISMS OF CELL INJURY
• GENERAL PRINCIPLES
1. The cellular response to injurious stimuli
depends on the type of injury, its duration,
and its severity.
–low doses of toxins or a brief duration of
ischemia -> reversible cell injury.
–larger toxin doses or longer ischemic
intervals -> irreversible injury and cell
death.
56

57. 2 .The consequences of an injurious
stimulus depend on
Cell type :
– skeletal muscle show no
irreversible injury after complete
ischemia for 2 to 3 hrs but
–cardiac muscle dies after only 20
to 30 minutes.
57

58. 3. Cellular function is lost far before cell death
occurs, and the morphologic changes of cell
injury (or death) lag far behind both.
• Onset of Injury viable but nonfunctional
cells  persistent injury irreversible
biochemical alterations leading to cell death
ultrastructural, light microscopic, and grossly
visible morphologic changes.
58

59. • Example
• myocardial cells –
–non contractile after 1 to 2 minutes of
ischemia
–die after 30 minutes of ischemia
–do not appear dead by ultrastructural
evaluation (electron microscopy) for 2 to 3
hours, and by light microscopy for 6 to 12
hours.
59

60. Sequential development of biochemical and morphologic changes
60

61. 4. Five intracellular systems are particularly vulnerable:
1. cell membrane integrity,
• critical to cellular ionic and osmotic homeostasis;
2. adenosine triphosphate (ATP) generation,
• largely via mitochondrial aerobic respiration;
3. protein synthesis; and
4. the integrity of the genetic apparatus.
5. the cytoskeleton
61

62. Biochemical basis of cell injury
1. Depletion of ATP
• Depletion of ATP to < 5% to 10% of normal levels has
widespread effects on many critical cellular systems.
• major causes :
– reduced supply of oxygen and nutrients
– mitochondrial damage, and
– the actions of some toxins (e.g., cyanide).
• Effect depends on glycolytic capacity of the tissue
(e.g. liver better survive than the brain)
62

63. Effects of ATP depletion
1. Anaerobic glycolysis is used for ATP synthesis and
is accompanied by:
a. Activation of phosphofructokinase caused by
low citrate levels and increased AMP
b. Decrease in intracellular pH caused by an
excess of lactate leading to decreased activity of
many cellular enzymes
2. Impaired Na, K+ -ATPase pump, resulting in
diffusion of Na+ and H20 into cells and causing
cellular swelling
63

64. 3. Impaired calcium (Ca 2+)-ATPase pump,
resulting in increased cytosolic Ca2+
4. Decreased protein synthesis, resulting from
the detachment of ribosomes from the rough
EPR
64

65. 65

66. 2.Influx of Calcium
• Increased cytosolic Ca2+ leads to:
1. Enzyme activation
-- phospholipase: increases membrane permeability
-- Proteases: damages membrane & structural proteins
-- Endonucleases: damages nuclear chromatin, causing
nuclear fading (karyolysis)
-- ATPases : hastens ATP depletion
2. Reentry of Ca2+ into mitochondria: increases
mitochondrial membrane permeability, with release
of cytochrome C (activates apoptosis)
66

67. 67

68. 3. Damage to Mitochondria
• There are two major consequences of
mitochondrial damage :
1. Formation of mitochondrial permeability
transition pore
– which leads to the loss of mitochondrial membrane
potential and pH changes  failure of oxidative
phosphorylation progressive depletion of ATP, 
culminating in necrosis of the cell
2. leakage of cytochrome into the cytosol death
by apoptosis
68

69. 69

70. • 4. Free radicals accumulation
• Free radicals are chemical species with a
single unpaired electron in an outer orbital
• Such chemical states are extremely unstable
and readily react with inorganic and organic
chemicals
• when generated in cells they avidly attack
nucleic acids as well as a variety of cellular
proteins and lipids
70

71. • Reactive oxygen species (ROS)
– oxygen-derived free radical
– has a well established role in cell injury
– produced normally in cells during mitochondrial
respiration and energy generation, but they are
degraded and removed by cellular defense systems.
• When the production of ROS increases or the
scavenging systems are ineffective, the result is
an excess of these free radicals, leading to a
condition called oxidative stress
71

72. Ischemia-Reperfusion Injury
• If cells are reversibly injured by ischemia, the
restoration of blood flow has two possible
effects
• 1. cell recovery-- in most cases
• 2. a paradoxical exacerbated injury--
occasionally
– This is so-called ischemia-reperfusion injury
– It contribute significantly to tissue damage in
myocardial and cerebral infarctions.
72

73. Mechanisms of reperfusion injuries
1. increased generation of ROS :
reoxygenation  incomplete reduction of oxygen by
the damaged mitochondria of parenchyma cells
and endothelial cells and from infiltrating
leukocytes.
2.Ischemic injury is associated with inflammation,
which may increase with reperfusion because of
increased influx of leukocytes and plasma proteins
– The products of activated leukocytes may cause
additional tissue injury
73

74. Thank you!
74

75. THE MORPHOLOGY OF CELL AND TISSUE INJURY
• Noxious stimuli  molecular or biochemical
alterations  cellular function lost 
morphologic changes of cell injury or death
• For example, :
- ischemic myocardial cells become non
contractile  then die  appear dead by EM
then LM
75

76. Morphologic correlates of reversible
cell injury
A. Cellular swelling
• Also called hydropic change or vacuolar
degeneration
• The first manifestation of almost all forms of injury
to cells
• it is the result of failure of energy-dependent ion
pumps in the plasma membrane, leading to an
inability to maintain ionic and fluid homeostasis.
• difficult to appreciate it with the light microscope
76

77. • Grossly
– pallor, increased turgor, and increase in weight of
the organ.
• Microscopic examination may reveal
– small, clear vacuoles within the cytoplasm;
• Which are distended and pinched-off segments of ER
77

78. B. Fatty change
• manifested by the appearance of lipid
vacuoles in the cytoplasm.
• It occurs mainly in cells involved in and
dependent on fat metabolism, such as
hepatocytes and myocardial cells.
78

79. • Ultrastructural changes of reversible cell injury :
(1) Plasma membrane alterations such as
blebbing, blunting or distortion of microvilli, and
loosening of intercellular attachments;
(2) Mitochondrial changes such as swelling
(3) Dilation of the ER with detachment of
ribosomes and dissociation of polysomes; and
(4) Nuclear alterations, with clumping of
chromatin.
79

80. Morphologic correlates of
irreversibility
• Two phenomena consistently characterize
irreversibility:
• 1.The inability to reverse mitochondrial
dysfunction (lack of oxidative phosphorylation
and ATP generation) even after resolution of
the original injury, and
• 2. profound disturbances in membrane
function
80

81. Cell death
81

82. Necrosis
• Necrosis is death of groups of cells, often
accompanied by an inflammatory infiltrate
• largely resulting from the degradative action of
enzymes on lethally injured cells derived from
– the lysosomes of the dying cells themselves or
– from the lysosomes of leukocytes that are recruited as
part of the inflammatory reaction to the dead cells
• Necrotic cells are unable to maintain membrane
integrity, and their contents often leak out
82

83. Morphology of necrotic cells
• They show increased eosinophilia
• have a more glassy homogeneous appearance
• Cytoplasm becomes vacuolated
• myelin figures accumulated
• Calcifications
83

84. • Ultrastructure morphologic changes of
necrotic cells
– Profound nuclear changes includes karyolysis,
pyknosis, karyorrhexis
84

85. Nuclear changes: - due to
nonspecific DNA breakdown
• Pyknosis = nuclear
condensation(shrinkage) and
↑ basophilia
• Karyorrhexis [rhexis,
rupture]= nuclear
fragmentation
• Karyolysis= loss of DNA → ↓
basophilia
85

86. Patterns of Tissue Necrosis
Coagulative necrosis
• when component of cells are dead but the basic
tissue architecture is preserved
• Injury denatures enzymes (in addition to
structural proteins) so blocks the proteolysis of
the dead cells anucleated cells may persist for
days or weeks architecture preserved.
• Coagulative necrosis is characteristic of infarcts
(areas of ischemic necrosis) in all solid organs
except the brain
86

87. *Gangrenous necrosis
• not a distinctive type of necrosis but
commonly used in clinical practice to a limb
that has lost its blood supply and undergone
coagulative necrosis
• when bacterial superinfection is
superimposed coagulative necrosis is
modified by the liquefactive action of the
bacteria and the attracted leukocytes (so-
called wet gangrene).
87

88. Bowel-gangrenous
Diabetic
gangrene
88

89. Liquefactive necrosis
• It Is necrotic degradation of tissue that softens and
becomes liquified
• Mechanism
• microbes  stimulate the accumulation of
inflammatory cells  enzymes of leukocytes digest the
tissue formation of liquid viscous mass
Examples
• 1. CNS infarction: autocatalytic effect of hydrolytic
enzymes generated by neuroglial cells produces a cystic
space
2. Abscess in a bacterial infection: hydrolytic enzymes
generated by neutrophils liquefy dead tissue
89

90. 90

91. Caseous necrosis
• The necrotic area appears friable yellow-white or
cheese-like thus called "caseous"
– formed by the release of lipid from the cell
walls of Mycobacterium tuberculosis and
systemic fungi (e.g., Histoplasma) after
destruction by macrophages.
• tissue architecture is completely obliterated and
cellular outlines cannot be discerned
91

92. 92

93. • Fat necrosis
• Refers to focal areas of fat destruction, typically
resulting from release of activated pancreatic
lipases into the substance of the pancreas and
the peritoneal cavity
• It is associated with acute pancreatitis
• Mechanisms
(1) Activation of pancreatic lipase (e.g., alcohol
excess): hydrolysis of triacylglycerol in fat cells
(2) Conversion of fatty acids into soap
(saponification): combination of fatty acids and
calcium
93

94. • Gross appearance:
– chalky yellow-white
deposits (fat
saponification)
– primarily located in
peripancreatic and
omental adipose
tissue.
94

95. • Non enzymatic fat necrosis
– results from hypoxic necrosis or mechanical injury
to fat cells.
– The fat liquefies at body temperature and is
released as an oily mass, resulting in formation of
oil cysts.
– Eg. In the breast following trauma
– In subcutaneous tissue
95

96. APOPTOSIS
• a pathway of cell death that is induced by a
tightly regulated suicide program
• cells destined to die activate enzymes capable
of degrading the cells' own nuclear DNA and
cellular proteins.
• (apoptosis, "falling off").
– fragments of the apoptotic cells then break off,
96

97. • The plasma membrane of the apoptotic cell
– remains intact but altered in such a way that the
cell and its fragments become avid targets for
phagocytes. Therefore
• dead cell is rapidly cleared before its contents have
leaked out
• cell death by appoptosis does not elicit an
inflammatory reaction in the host.
97

98. • apoptosis differs from necrosis, which is
characterized by loss of membrane integrity,
enzymatic digestion of cells, leakage of cellular
contents, and frequently a host reaction
• However, apoptosis and necrosis sometimes
coexist, and apoptosis induced by some
pathologic stimuli may progress to necrosis.
98

99. Physiologic role of apoptosis:
• 1. The programmed destruction of cells
during embryogenesis, .
• 2. Involution of hormone-dependent tissues
upon hormone deprivation,
• 3.Cell loss in proliferating cell populations to
maintain a constant number,
99

100. • 4.Death of cells that have served their useful
purpose,
– such as neutrophils and lymphocytes at the end of
an immune response
• 5.Elimination of potentially harmful self-reactive
lymphocytes,
• 6.Cell death induced by cytotoxic T lymphocytes,
– to kill and eliminate virus-infected and neoplastic
cells
100

101. Apoptosis in Pathologic Conditions :
• 1. DNA damage
– Radiation, cytotoxic anticancer drugs and hypoxia
can damage DNA,
– either directly or via production of free radicals
– If repair mechanisms cannot cope with the injury,
the cell triggers intrinsic mechanisms that induce
apoptosis
– larger doses of the same stimuli result in necrosis
101

102. • 2. Accumulation of misfolded proteins
– resulted due to
• mutations in the genes encoding proteins or
free radicals damage
• Excessive accumulation of these proteins in the
ER  ER stress apoptotic death of cells
102

103. • 3. Cell injury in certain infections, particularly viral
infections,
– Apoptosis induced by
• the virus (as in adenHIV infections) or
• the host immune response (as in viral hepatitis)
• 4. Pathologic atrophy in parenchymal organs after
duct obstruction,
– such as occurs in the pancreas, parotid gland, and
kidney
103

104. Mechanism of Apoptosis
• Two distinct pathways for caspase activation
– the mitochondrial pathway and
– the death receptor pathway
• Both differ in their induction and regulation,
but culminate in the activation of
"executioner" caspases
104

105. Mitochondrial (Intrinsic) Pathway of Apoptosis
Injurious agent  DNA damage or
accumulation of misfolded ptn  activation of
pro apoptotic members of BCL2 family
(Bax,Bak) inserted into mitochondrial
membrane to form channel cytochrom C
and other ptns escape to cytosol  activate
caspases  nuclear fragmentation
105

106. Death Receptor (Extrinsic) Pathway of Apoptosis
• Many cells express surface molecules, called
death receptors, that trigger apoptosis.
106

107. 107

108. PATHOLOGIC CALCIFICATION
• An abnormal deposition of calcium salts, together with smaller
amounts of iron, magnesium, and other minerals
• it is a common process in a wide variety of disease states
• Of two type
1. Dystrophic calcification
- When the deposition occurs in dead or dying tissues
- it occurs in the absence of calcium metabolic derangements (i.e.,
with normal serum levels of calcium).
2. metastatic calcification
- the deposition of calcium salts in normal tissues
- almost always reflects hypercalcemia
 NB. hypercalcemia is not a prerequisite for dystrophic calcification
but it can exacerbate it.
108

109. Dystrophic Calcification
• Dystrophic calcification: deposition of calcium at sites
of cell injury and necrosis
• It is virtually inevitable in the atheromas of advanced
atherosclerosis, associated with intimal injury in the
aorta and large arteries and characterized by
accumulation of lipids
• Although dystrophic calcification may be an incidental
finding indicating insignificant past cell injury, it may
also be a cause of organ dysfunction.
• For example, calcification can develop in aging or
damaged heart valves, resulting in severely
compromised valve motion.
109

110. 110

111. Metastatic Calcification
• Metastatic calcification can occur in normal
tissues whenever there is hypercalcemia.
• The four major causes of hypercalcemia are :
• (1) increased secretion of parathyroid
hormone, due to either primary parathyroid
tumors or production of parathyroid
hormone-related protein by other malignant
tumors;
• (2) destruction of bone due to the effects of
accelerated turnover (e.g., Paget disease),
immobilization, or tumors (increased bone
catabolism associated with multiple myeloma)
111

112. • (3) vitamin D-related disorders including
vitamin D intoxication and sarcoidosis (in
which macrophages activate a vitamin D
precursor); and
• (4) renal failure, in which phosphate retention
leads to secondary hyperparathyroidism.
112

113. THANK YOU!