Patho by Dr.Elnemr [108][Part.1]

P
ATHOLOGY
CHAPTER 1
1
STYEAR-MODULE1
08
KASRALAI
NYUNI
VERSI
TY
DRAHMEDELNEMR
Pathology New Edition DR.Elnemr
Cellular Response to Injury

Normal cell function requires a balance between physiologic demands and the limitations of
cell structure and metabolic capacity; the result is a steady state, or homeostasis.
Cells can alter their functional state in response to modest stress to maintain the steady state.
More excessive physiologic stresses, or adverse pathologic stimuli (injury), result in:
1) Adaptation.
2) Reversible Injury, or Irreversible Injury and cell death.
NB: These responses may be considered a continuum of progressive impairment of cell

structure and function.
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1. Adaptation
➢ It occurs when physiologic or pathologic stressors induce a new state that changes the cell
but otherwise preserves its viability in the face of the exogenous stimuli.
➢ These changes include:
A. Atrophy.
B. Hypertrophy.
C. Hyperplasia.
D. Metaplasia.
2. Reversible Injury
➢ It denotes pathologic cell changes
➢ It can be restored to normally if the stimulus is removed or if the cause of injury is mild.
3. Irreversible Injury
➢ It denotes permanent pathologic changes that cause cell death.
➢ It occurs when stressors exceed the capacity of the cell to adapt
(Beyond a point of no return) ‫نقطه الالعوده‬
2|Page
Causes Of Cell Injury:

1) Oxygen deprivation (hypoxia)
➢ It affects aerobic respiration and therefore the ability to generate adenosine
triphosphate (ATP).
➢ This extremely important and common cause of cell injury and death.
➢ Hypoxia occurs as a result of:
• Ischemia (deficient blood supply).
• Inadequate oxygenation (e.g., cardiorespiratory failure).
• Loss of oxygen-carrying capacity of the blood
(e.g., anemia, carbon monoxide poisoning).
2) Physical agents including trauma, heat, cold, radiation, and electric shock.
3) Chemical agents and drugs, including therapeutic drugs, poisons, environmental

pollutants, alcohol and narcotics.
4) Infectious agents, including viruses, bacteria, fungi, and parasites.
5) Immunologic reactions, including autoimmune diseases, and cell injury following

responses to infection.
6) Genetic derangements, such as chromosomal alterations and specific gene mutations.
7) Nutritional imbalances, including protein-calorie deficiency or lack of specific vitamins,

as well as nutritional excesses.
3|Page
Mechanisms Of Cell Injury

The degree of injury depends on
1) Duration and persistence of injury,
2) Nature of injurious agent
3) Type of cells affected.
Cell injury occurs by the following mechanisms:
1. Interference with aerobic respiration in mitochondria (oxidative phosphorylation)

➢ This leads to reduction of ATP and therefore impairs biochemical processes in the cell,
with the following effects:
i. Reduction of activity of sodium pump,
leading to accumulation of sodium inside the cell
with influx of water into the cell causing it to swell (cytomegaly)
ii. Interferes with protein synthesis.
iii. Increase of intracellular calcium
(The calcium levels are kept in check by ATP-dependent enzymes).
4|Page
2. Accumulation of reactive oxygen species (oxidative stress) (‫)حاول تقسم الجزء‬

Definition:
➢ Free radicals, including reactive oxygen species are chemical species that
have a single unpaired electron in an outer orbit.
➢ They are highly reactive thus interact and alter adjacent molecules.
The source:
They are produced normally in small amounts
• During The Reduction-Oxidation Reactions
• During Mitochondrial Respiration
• Energy Generation.
Examples of oxidants:
Reactive oxygen species include:
• superoxide (02-)
• hydroxyl radical (OH-)
• hydrogen peroxide (H2O2).
Examples of Anti-oxidants: Oxidants Anti-
Oxidants
• vitamin E
• enzymes such as superoxide dismutase
Normally:
➢ there is a balance between free radicals and defense mechanisms which includes
antioxidants as vitamin E and enzymes such as superoxide dismutase.
In some situations:
➢ The defense mechanisms are overcome and free radicals interact with
• Lipids In Cell Membranes (Peroxidation),
• Cellular Proteins
• DNA,
(This Is Referred to As Oxidative Stress)

Free radicals play a major role in
i. Reperfusion Injury (following restoration of blood flow in ischemic tissue),
ii. Cellular Aging,
iii. Chemical Injury
iv. Radiation Damage.
5|Page
3. Disruption of membranes:
A common result of the above mechanisms is disturbance of the function of membranes.
• ATP depletion affects the Na pump of plasma membrane.

✓ Increase intracellular calcium causes activation of
phospholipases which break down membranes.
• Free radical peroxidation of lipids in membranes further damages the structure.
• Disruption of lysosomal membranes
✓ leads to release of various enzymes including
DNases, and proteases, into the cytosol leading to death of the cell.
Notes:
…………………………………………………………………………………
…………………………………………………………………………………
…………………………………………………………………………………
…………………………………………………………………………………
…………………………………………………………………………..
.……………………………………………………………………….
.
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Morphologic Alternations in Cell Injury
1. Reversible Injury (Degeneration):

A- Cloudy Swelling:
Definition: One of the earliest changes seen in injury
causes:
➢ loss of Na pump
➢ accumulation of sodium and water inside the cell.
Morphology:
➢ The cell is swollen and the cytoplasm appears granular.
Site: It is seen in liver cells, myocardial cells and renal tubular cells.
B- Hydropic, Ballooning or Vacuolar Change:

➢ Same mechanism as cloudy swelling but more advanced.
➢ The cells are swollen due to excess water accumulation.
➢ The cytoplasm is pale and shows multiple vacuoles.
C- Fatty Change:
➢ Fatty change occurs in hypoxic and toxic injury.
➢ Lipid appears as empty vacuoles in the cytoplasm.
➢ It is seen in cells involved in or dependent on fat metabolism,
such as hepatocytes and myocardial cells.
➢ Fatty change in myocardium can be
• Spotty (in case of ischemia) or
• Diffuse (in case of toxemia e.g., in diphtheria).
(See fatty change of the liver in chapter 2)
7|Page
2- Irreversible Injury:
➢ Cell death occurs primarily through two morphologic patterns and mechanisms:
Necrosis And Apoptosis.
NECROSIS
Definition: Necrosis is death of a group of cells within a living body.
 With severe or prolonged moderate injury,

there is loss of membrane integrity and release of lysosomal enzymes in the cytosol
leading to destruction of the cellular constituents.
 There is also leakage of cell constituents into the surrounding tissue,
resulting in an inflammatory response.
 Necrotic area is removed by macrophages and repaired by fibrosis.
 Dystrophic calcification may occur.
Mechanism:
➢ Two processes underlie the basic morphologic changes:
1) Denaturation of proteins.
2) Enzymatic digestion of organelles and other cytosolic components.
Morphology:
➢ There are several distinctive features:
1- Nuclear Changes:
➢ Pyknosis: Nuclear shrinkage.
➢ Karyorrhexis: Destructive nuclear fragmentation.
➢ Karyolysis: Fading of nuclear basophilia.
 Eventually the nucleus disappears completely.
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2- Cytoplasmic Changes:
➢ Necrotic cells are more eosinophilic
(Stain more pink) with hematoxylin and eosin Due To
1) loss of cytoplasmic RNA which binds the blue dye (hematoxylin)
2) presence of denatured cytoplasmic proteins which bind the red dye (eosin).
➢ There is loss of cell border definition.
➢ Later the necrotic tissue appears structureless pink
due to autolysis by lysosomal enzymes.
Normal
Reversible
Necrosis
9|Page
Types of necrosis:
1. Coagulative necrosis (ischemic necrosis):
Etiology:
 It occurs as a result of acute ischemia (sudden decrease in blood supply).
Pathogenesis:
➢ It is due to protein denaturation.
➢ Presumably, the injury denatures structural proteins, as well as the enzymes that cause
proteolysis (autolysis) so the cellular outlines are maintained for some time.
(Ghost Cell)
SITE:
 Any Organs except Brain
e.g.: infarction of kidney, spleen and heart.
Morphology:
Gross picture:
• The necrotic area is initially

white/yellow but of normal consistency ,
Microscopic picture:
• loss of nuclei.
• increased eosinophilia of the cytoplasm with retention of the general cellular outline
(Appearing as ghost of the original tissue).
• Eventually, this cellular outline is lost and tissues break down and
appear structureless pink.
• Inflammatory cells infiltrate the necrotic tissue and macrophages remove the dead
tissue.
2. Liquefactive or colliquative necrosis: Occurs in

A. CNS infarctions, where the tissues are
Rich in lipid, Soft and Lack supporting stroma.
• Necrotic area becomes surrounded
by glial tissue and is changed into a cyst.
B. Pus in suppurative inflammation.
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3. Caseation Necrosis:
It is a type of necrosis where the necrotic tissue appears
 semi-solid,
 yellowish and cheese-like (casein).
Microscopic Picture:
➢ appears as granular structureless pink material.
Pathogenesis:
➢ This occurs mainly in Tuberculosis due to tissue digestion by activated macrophages.

➢ Also, liberation of lipids from the tubercle bacilli capsule adds to the cheese-like
appearance.
4. Fat Necrosis :is of two types:

A- Traumatic Fat Necrosis: B- Enzymatic Fat Necrosis:
Site: Site:
 A common site is the breast where it  Pancreas
results in a palpable mass. Pathogenesis:
Pathogenesis: ➢ In acute pancreatitis, there is leakage of
➢ Trauma to adipose tissue leads to the pancreatic lipase,
release of intracellular fat which which acts on mesenteric fat cells splitting
provokes an inflammatory response. fat into fatty acids,
➢ Macrophages engulf the fat and which combine with calcium to form
eventually lead to fibrosis. white calcium soaps.
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5. Fibrinoid necrosis:
Definition:
 Fibrinoid necrosis is a special form of necrosis,

 where the necrotic material has some staining reactions resembling fibrin.
Morphology:
➢ The material is Deep Red and Homogenous with Hematoxylin and eosin stain.
Causes:
➢ It is seen with collagen damage in

• some autoimmune diseases as rheumatoid arthritis and
• in immune reactions involving blood vessels, e.g., polyarteritis nodosa.
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APOPTOSIS
Definition: Apoptosis means falling away in Greek.
 It is a programmed cell death which is energy dependent.

 It is a form of cell death which leads to the deletion of individual cells.
 Their membranes remain intact and thus do not provoke an inflammatory response.
Causes of apoptosis:
➢ It can occur in physiologic and pathological conditions.
1. Apoptosis in physiological conditions:

A. Programmed destruction of cells during embryogenesis.
B. Hormone dependent involution of tissues e.g., in the endometrium during
menstruation.
C. Cell deletion in proliferating cell populations (e.g., intestinal epithelium) to
maintain a constant cell number.
D. Defective cells which acquire significant DNA damage are removed by apoptosis,
to get rid of cells with unwanted mutations.
2. Apoptosis in pathological conditions:
A. Cell death in virus infected cells, which may be induced by the virus as in
HIV infection or by the host immune response e.g., viral hepatitis.
B. Irradiation damage (DNA damage).
C. Elimination of cancer cells (including action of anticancer drugs).
D. Cytotoxicity induced by T lymphocytes as in organ transplant rejection.
E. Accumulation of misfolded proteins
• (e.g., due to inherited defects or due to free radical damage).
• This may be the basis of cell loss in a number of neurodegenerative disorders.
F. Pathologic atrophy in parenchymal organs after duct obstruction (e.g., pancreas).
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Morphological Changes:
➢ The cytoplasm condenses and the cell shrinks,
retaining an intact plasma membrane.
➢ The nucleus shrinks and fragments.
➢ Apoptotic cells show surface blebs which
later fragment into membrane bound apoptotic bodies,
consisting of a dark nuclear fragment surrounded by
eosinophilic cytoplasm.
➢ Apoptotic cells and apoptotic bodies are removed by
adjacent cells or macrophages.
➢ Control of Apoptosis:
 Apoptosis is controlled by the Bcl2 protein family.
 Apoptosis is brought about by activation of

a group of enzymes called caspases.
 These enzymes result in destroying
the nuclear membrane and
activate DNases which degrade nuclear DNA.
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MCQ On Chapter 1
1) The mildest and commonest type of degeneration is:
a) Hyaline degeneration
b) Cloudy swelling.
c) Amyloid degeneration
d) Fatty degeneration.
2) Cell response to injurious stimuli depends on

a) Type of injury
b) Duration of exposure to injury
c) Cell type
d) All of the above
3) Changes associated with water metabolism are EXCEPT

a) Irreversible cell injury
b) Cellular edema
c) Normal nucle.
d) Energy defect
4) Cloudy swelling occurs in:

a) Parenchymatous cells.
b) Muscle cells.
c) Connective tissue fibroblasts
d) Non of the above.
5) Which of the following is a reversible damage?

a) Karyorrhexis .
b) Pyknosis.
c) Karryolysis
d) Swelling of endoplasmic reticulum.
1- B 2- D 3- A 4- A 5- D
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6) Which of the following is a reversible change?

a) Karyorrhexis.
b) Pyknosis.
c) Karyolysis.
d) Swelling of endoplasmic reticulum.
e) Gangrenous necrosis.
7) Enzymatic digestion is the predominant event in the following type of

necrosis:
a) Coagulative necrosis.
b) Liquefactive necrosis
c) Caseous necrosis.
d) Fat necrosis
8) In hypoxic cell injury swelling of the cell occurs because

intracytoplasmic accumulation of:
a) Lipids.
b) Proteins.
c) Glycogen.
d) Lipofuscin
e) Water.
9) Fibrinoid necrosis is found in the following EXCEPT:

a) Rheumatoid arthritis
b) Necrotizing arteriolitis in malignant hypertension
c) acute hemorrhagic pancreatic necrosis
d) Systemic lupus erythematosus
10) Fat necrosis is usually due to

a) Autoimmune reaction
b) Traumatic
c) Ischemia
d) None of the above.
6- D 7- B 8- E 9- C 10- B
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11) All are correct about Necrosis EXCEPT:

a) Local death of small or large group of cells in living tissue.
b) opaque white with hyperemia in the surrounding tissues.
c) Nuclei of the cells are not affected .
d) It often occurs due to ischemia.
12) Necrosis of the following lesions is liquefactive type EXCEPT:

a) An abscess.
b) Brain infarction.
c) Renal infarction
d) Amoebic liver abscess.
13) All the following are signs of necrosis EXCEPT:

a) Lipofuscin
b) Pyknosis.
c) Karyolysis.
d) Karyorrhexis.
14) Coagulation necrosis occurs in all EXCEPT:

a) Kidney.
b) Heart.
c) Spleen.
d) Central nervous system.
15) Liquefactive ischemic necrosis is especially seen in:

a) Heart.
b) Brain.
c) Spleen.
d) Kidney.
11- C 12- C 13- A 14- D 15- B
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16) A 76-year-old develops signs and symptoms suggestive of Myocardial

infarction. Microscopic examination of the heart is most Likely to reveal:
A. Caseous necrosis.
B. Coagulative necrosis.
C. Enzymatic fat necrosis.
D. Gangrenous necrosis.
E. Liquefactive necrosis.
17) In the process of necrosis, a reduction in the size of the nucleus and a
condensation of nuclear material is known as:
a) Pyknosis
b) Karyolysis.
c) Karyorrhexis
d) Metachromasia.
e) Hypochromasia
18) The underlying tissue damage in most cases of hemorrhagic

Infarction of the lung is:
a) Caseous necrosis.
b) coagulation necrosis.
c) Fibrinoid necrosis.
d) Gangrenous necrosis.
e) Liquefactive necrosis.
19) of the following, caseous necrosis would most likely be Associated

with:
a) Pulmonary tuberculosis
b) Soft tissue abscesses.
a) Sore throat.
b) Thrombophlebitis.
c) Viral bronchitis.
16- B 17- A 18- B 19- A
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20) Which type of the following types of necrosis is grossly opaque and
chalky white
a) Coagulative.
b) Liquefactive.
c) Caseous necrosis
d) Fat necrosis.
21) Cell or tissue death within the living body is termed:

a) Lysis.
b) phagocytosis.
c) pyknosis
d) necrosis
e) Karyolysis.
22) Caseous necrosis is most commonly in which of the Following

disease processes?
a) Tuberculosis
b) Pneumonia.
c) Syphilis.
d) Scarlet fever.
e) Chickenpox.
23) A type of necrosis present in tuberculosis:
a. Coagulative necrosis.
b. Caseation necrosis.
c. Liquefactive necrosis.
d. Enzymatic fat necrosis.
e. Traumatic fat necrosis.
24) Acute pancreatitis is characterized by:
b) Caseous necrosis
c) Fat necrosis,
d) Fibrinoid necrosis.
e) Liquefactive necrosis.
20- D 21- D 22- A 23- B 24- C
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25) Localized area of ischemic necrosis is mostly associated with:

a) Ascites.
b) Petechiae
c) infarction.
d) Emboli formation.
e) Hematoma.
26) Apoptosis has the following features EXCEPT:

a. There is cell shrinkage in apoptosis.
b. There are no acute inflammatory cells surrounding apoptosis.
c. There may be single cell loss or affect clusters of cells.
d. Apoptosis is seen in pathologic processes only.
27) Apoptosis occurs in all EXCEPT:

a) During embryogenesis
b) Viral hepatitis.
c) Menstruation
d) Tuberculosis.
28) Apoptosis is characterized by the following Except

a) Cell shrinkage.
b) Cytoplasmic blebs.
c) Cell membrane rupture
d) Formation of apoptotic bodies.
29) Apoptosis ends by:

a- Fibrosis.
b- Phagocytosis of apoptotic bodies.
c- Giant cell reaction.
d- All of the above.
25- C 26- D 27- D 28- C 29- B
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30) Active programmed cell death is called

b) Fat necrosis.
c) Autolysis.
d) Apoptosis
31) Apoptosis causes EXCEPT:

a) Activation of caspases.
b) Local inflammatory response.
c) Phagocytosis of celt fragment by local macrophages.
d) Condensation of chromatin.
32) Features of apoptosis include all the following except:

a. Shrinkage of cell size.
b. Nuclear chromatin condensation.
c. Formation of membrane blebs.
d. Inflammation.
e. DNA fragmentation.
33) Apoptosis is brought about by a group of enzymes called

a) Lipases.
b) Proteases.
c) Caspases.
d) Catalases.
30) D 31) B 32) D 33) C
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Cellular Response to Injury

NB: These responses may be considered a continuum of progressive impairment of cell

Causes Of Cell Injury:

3) Chemical agents and drugs, including therapeutic drugs, poisons, environmental

4) Infectious agents, including viruses, bacteria, fungi, and parasites.

5) Immunologic reactions, including autoimmune diseases, and cell injury following

6) Genetic derangements, such as chromosomal alterations and specific gene mutations.

7) Nutritional imbalances, including protein-calorie deficiency or lack of specific vitamins,

Mechanisms Of Cell Injury

1. Interference with aerobic respiration in mitochondria (oxidative phosphorylation)

2. Accumulation of reactive oxygen species (oxidative stress) (‫)حاول تقسم الجزء‬

(This Is Referred to As Oxidative Stress)

• ATP depletion affects the Na pump of plasma membrane.

Morphologic Alternations in Cell Injury

1. Reversible Injury (Degeneration):

B- Hydropic, Ballooning or Vacuolar Change:

(See fatty change of the liver in chapter 2)

 With severe or prolonged moderate injury,

➢ Karyorrhexis: Destructive nuclear fragmentation.

➢ Karyolysis: Fading of nuclear basophilia.

 Eventually the nucleus disappears completely.

• The necrotic area is initially

2. Liquefactive or colliquative necrosis: Occurs in

➢ This occurs mainly in Tuberculosis due to tissue digestion by activated macrophages.

4. Fat Necrosis :is of two types:

 Fibrinoid necrosis is a special form of necrosis,

➢ It is seen with collagen damage in

 It is a programmed cell death which is energy dependent.

1. Apoptosis in physiological conditions:

2. Apoptosis in pathological conditions:

 Apoptosis is brought about by activation of

2) Cell response to injurious stimuli depends on

3) Changes associated with water metabolism are EXCEPT

4) Cloudy swelling occurs in:

5) Which of the following is a reversible damage?

6) Which of the following is a reversible change?

7) Enzymatic digestion is the predominant event in the following type of

8) In hypoxic cell injury swelling of the cell occurs because

9) Fibrinoid necrosis is found in the following EXCEPT:

10) Fat necrosis is usually due to

11) All are correct about Necrosis EXCEPT:

12) Necrosis of the following lesions is liquefactive type EXCEPT:

13) All the following are signs of necrosis EXCEPT:

14) Coagulation necrosis occurs in all EXCEPT:

15) Liquefactive ischemic necrosis is especially seen in:

11- C 12- C 13- A 14- D 15- B

16) A 76-year-old develops signs and symptoms suggestive of Myocardial

18) The underlying tissue damage in most cases of hemorrhagic

19) of the following, caseous necrosis would most likely be Associated

16- B 17- A 18- B 19- A

21) Cell or tissue death within the living body is termed:

22) Caseous necrosis is most commonly in which of the Following

20- D 21- D 22- A 23- B 24- C

25) Localized area of ischemic necrosis is mostly associated with:

26) Apoptosis has the following features EXCEPT:

27) Apoptosis occurs in all EXCEPT:

28) Apoptosis is characterized by the following Except

29) Apoptosis ends by:

25- C 26- D 27- D 28- C 29- B