Cell Injury & Death

General Pathology
Lab II

Mahmoud Kiswani, MD
What are the cellular changes of cell injury ?
Case 1
• A 53-year-old man has had severe chest pain for the past 6 hours. On physical
examination he is afebrile, but has tachycardia. Laboratory studies show a serum
troponin I of 10 ng/mL. A coronary angiogram is performed emergently and reveals >90%
occlusion of the anterior interventricular (left anterior descending) artery. In this setting, an
irreversible injury to myocardial fibers will have occurred when which of the following
cellular changes occurs?
• A Glycogen stores are depleted
• B Cytoplasmic sodium increases
• C Nuclei undergo karyorrhexis
• D Intracellular pH diminishes
• E Blebs form on cell membranes
Case 1
• A 53-year-old man has had severe chest pain for the past 6 hours. On physical
examination he is afebrile, but has tachycardia. Laboratory studies show a serum
troponin I of 10 ng/mL. A coronary angiogram is performed emergently and reveals >90%
occlusion of the anterior interventricular (left anterior descending) artery. In this setting, an
irreversible injury to myocardial fibers will have occurred when which of the following
cellular changes occurs?
• A Glycogen stores are depleted
• B Cytoplasmic sodium increases
• C Nuclei undergo karyorrhexis
• D Intracellular pH diminishes
• E Blebs form on cell membranes
Nuclear changes:
• Changes in the nucleus in necrosis:
• Pyknosis: increased basophilia due to shrinkage
of the nucleus.
• Karyorrhexis: fragmentation of the pyknotic
nucleus by nucleases
• Karyolysis: loss of the basophilia of the
chromatin, 2ry to DNAase activity.
Case 2
• A 79-year-old man has a large myocardial infarction involving much of the left ventricular
free wall. He develops congestive heart failure (CHF) with decreased cardiac output. Now,
a year later, his CHF is worsening. By echocardiography there is a large, bulging akinetic
area typical for a left ventricular aneurysm. Which of the following laboratory tests on
serum would best indicate poor peripheral tissue perfusion in this patient?
• A Elevated troponin I
• B Increased sodium
• C Elevated lactate
• D Increased hematocrit
• E Increased sedimentation rate
Case 2
• A 79-year-old man has a large myocardial infarction involving much of the left ventricular
free wall. He develops congestive heart failure (CHF) with decreased cardiac output. Now,
a year later, his CHF is worsening. By echocardiography there is a large, bulging akinetic
area typical for a left ventricular aneurysm. Which of the following laboratory tests on
serum would best indicate poor peripheral tissue perfusion in this patient?
• A Elevated troponin I
• B Increased sodium
• C Elevated lactate
• D Increased hematocrit
• E Increased sedimentation rate
Case 3
• A 77-year-old man with hypertension, type 2 diabetes mellitus, and
atrial fibrillation is admitted to the hospital because of a 3-
hour history of nausea and flank pain. Two days after admission, he
suddenly develops aphasia and left-sided paralysis. Despite
appropriate life-saving measures, he dies. A photograph of a section
of the kidney obtained at autopsy is shown. Microscopic examination
of the pale region in the photograph shows preserved cellular
architecture with eosinophilic cytoplasm and no visible nuclei. Which
of the following pathological changes is most likely responsible for the
renal findings on autopsy?
• Coagulative necrosis
• Non-enzymatic fat necrosis
• Gangrenous necrosis
• Liquefactive necrosis
• Fibrinoid necrosis
• Caseous necrosis
• Coagulative necrosis
• Non-enzymatic fat necrosis
• Gangrenous necrosis
• Liquefactive necrosis
• Fibrinoid necrosis
• Caseous necrosis
Question 4
• What is the type of necrosis in this image ?

• What is the morphological type of infarction ?

Question 5

myocardial infarct
• What is the type of necrosis in this image ?

• What is the morphological type of infarction ?

Case 6
• A 64-year-old woman is brought to the emergency department 30
minutes after the onset of right-sided weakness and impaired speech.
On admission, she is diagnosed with thrombotic stroke and treatment
with alteplase is begun. Neurologic examination four weeks later
shows residual right hemiparesis. A CT scan of the head shows
hypoattenuation in the territory of the left middle cerebral artery.
Which of the following processes best explains this finding?
• Gangrenous necrosis
• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fibrinoid necrosis
• Fat necrosis
• Gangrenous necrosis
• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fibrinoid necrosis
• Fat necrosis
Give another example for liquefactive necrosis?
Case 7
• A 34-year-old woman comes to the physician a week after noticing
a lump in her left breast. Three months ago, she was discharged from
the hospital after treatment of multiple injuries sustained in a motor
vehicle collision. Her only medication is an oral contraceptive. Her
mother died of ovarian cancer. Examination shows a 2.5-
cm, nontender mass in the upper outer quadrant of the left breast.
Mammography shows a circumscribed radiolucent lesion with a rim
of peripheral calcification. A photomicrograph of tissue from a biopsy
of the mass is shown. Which of the following is the most likely cause
of the breast swelling?
• Thrombophlebitis of subcutaneous veins
• Stimulation of estrogen receptors
• Defect in DNA repair
• Obstruction of lactiferous ducts
• Release of cytoplasmic triglycerides
• Thrombophlebitis of subcutaneous veins
• Stimulation of estrogen receptors
• Defect in DNA repair
• Obstruction of lactiferous ducts
• Release of cytoplasmic triglycerides
Case 8
• A 40-year-old woman has the sudden onset of severe abdominal pain. On physical
examination she has diffuse tenderness in all abdominal quadrants, with marked guarding
and muscular rigidity. She has laboratory findings that include serum AST of 43 U/L, ALT
of 30 U/L, LDH 630 U/L, and lipase 415 U/L. An abdominal CT scan reveals peritoneal
fluid collections and decreased attenuation along with enlargement of the pancreas.
Which of the following cellular changes is most likely to accompany these findings?
• A Coagulative necrosis
• B Dry gangrene
• C Fat necrosis
• D Apoptosis
• E Liquefactive necrosis
Case 8
• A 40-year-old woman has the sudden onset of severe abdominal pain. On physical
examination she has diffuse tenderness in all abdominal quadrants, with marked guarding
and muscular rigidity. She has laboratory findings that include serum AST of 43 U/L, ALT
of 30 U/L, LDH 630 U/L, and lipase 415 U/L. An abdominal CT scan reveals peritoneal
fluid collections and decreased attenuation along with enlargement of the pancreas.
Which of the following cellular changes is most likely to accompany these findings?
• A Coagulative necrosis
• B Dry gangrene
• C Fat necrosis
• D Apoptosis
• E Liquefactive necrosis
Case 9
This 70-year-old man was admitted to the hospital with a history of
upper abdominal pain, anorexia, nausea, and general malaise, all of
approximately three weeks' duration. His hospital stay was
characterized by fever and severe respiratory distress. There were
multiple densities in the patient's chest x-ray consistent with
pneumonia and examination of a stained sputum specimen showed
acid fast bacilli. Despite intensive therapy, the patient progressively
deteriorated and died 14 days after admission.
What is the type of necrosis ?

Other example’s?
Tuberculosis of the lung, with a large area of
Microscopic
caseous necrosis containing yellow-white
(cheesy) debris.
cheesy-appearing nodules (arrows) in the lymph nodes give
rise to the descriptive terminology of caseous necrosis.

The black pigment in the

lymph nodes is
anthracotic pigment
 Case 10
• A 60-year-old woman has noted a dark red-black appearance to
her great toe and second and third toes of her left foot for the past
month. On physical examination, the toes are cold and have no
sensation to touch. The dorsalis pedis and posterior tibial pulses
are not palpable on the left. A transmetatarsal amputation is
performed. These findings are most typical for a patient with
which of the following conditions?
 Case 10

• A Diabetes mellitus
• B Gout
• C Blunt force trauma
• D AIDS
• E Rheumatoid arthritis
 Case 11
• A 55-year-old man has a 30-year history of poorly controlled
diabetes mellitus. He has had extensive black discoloration of
skin and soft tissue of his right foot, with areas of yellowish
exudate, for the past 2 months. Staphylococcus aureus is cultured
from this exudate. A below-the-knee amputation is performed. The
amputation specimen received in the surgical pathology
laboratory is most likely to demonstrate which of the following
pathologic abnormalities?
 Case 11
• A Fibrinoid necrosis
• B Wet Gangrene
• C Vasculitis
• D Dry gangrene
• E fat necrosis
Question 12: Bowel
• What is the type of necrosis in these images ?

• What is the possible cause of this injury ?

Question 13:
What is the type of necrosis ?

What are the causes ?

Apoptosis
Case 14
At the end of a normal menstrual cycle, the endometrium sloughs.
Examination of the endometrium microscopically shows cellular
fragmentation. Which of the following is most likely to trigger apoptosis in
these endometrial cells?
• A Acute inflammation
• B Hypoxia
• C p53 protein accumulation
• D Decreased estrogen
• E Anaerobic glycolysis
Case 14
At the end of a normal menstrual cycle, the endometrium sloughs.
Examination of the endometrium microscopically shows cellular
fragmentation. Which of the following is most likely to trigger apoptosis
in these endometrial cells?
• A Acute inflammation
• B Hypoxia
• C p53 protein accumulation
• D Decreased estrogen
• E Anaerobic glycolysis
Case 15
An investigator is studying intracellular processes in muscle tissue after
denervation. A biopsy specimen is obtained from the biceps femoris
muscle of an 82-year-old woman who sustained sciatic nerve injury.
Investigation of the tissue specimen shows shrunken cells with dense
eosinophilic cytoplasm, nuclear shrinkage, and plasma membrane
blebbing. Which of the following best explains the muscle biopsy
findings?
Case 15
• Overexpression of Bcl-2
• Release of mitochondrial cytochrome c
• Degradation of Bcl-2-associated X protein
• Denaturation of cytoplasmic proteins
• Deactivation of caspases
• Inhibition of Fas/FasL interaction
Case 15
• Overexpression of Bcl-2
• Release of mitochondrial cytochrome c
• Degradation of Bcl-2-associated X protein
• Denaturation of cytoplasmic proteins
• Deactivation of caspases
• Inhibition of Fas/FasL interaction
Case 16
An investigator is studying the normal process of shrinking of the
thymus gland with increasing age in humans. Thymic size is found to
gradually start decreasing during puberty. Which of the following
enzymes is most likely involved in the process underlying the decline in
thymus mass with aging?
Case 16
• Lipase
• Metalloproteinase
• Caspase
• NADPH oxidase
• Collagenase
• Lipoxygenase
Case 17
• Lipase
• Metalloproteinase
• Caspase
• NADPH oxidase
• Collagenase
• Lipoxygenase
Case 18
During an experiment, an investigator attempts to determine the rates
of apoptosis in various tissue samples. Injecting cytotoxic T cells into
the cell culture of one of the samples causes the tissue cells to undergo
apoptosis. Apoptosis is most likely due to secretion of which of the
following substances in this case?
Case 18
• Cytochrome C
• Bcl-2
• TNF-α
• BAX
• Granzyme B
• Caspases
• FasL
Case 18
• Cytochrome C
• Bcl-2
• TNF-α
• BAX
• Granzyme B
• Caspases
• FasL
Calcification
Case 19
• A 72-year-old man died suddenly from congestive heart failure. At
autopsy, the heart weighed 580 g and showed marked left ventricular
hypertrophy and minimal coronary arterial atherosclerosis. A serum
chemistry panel ordered before death showed no abnormalities.
Which of the following pathologic processes best accounts for the
appearance of the aortic valve seen in the figure?
•□ (A) Amyloidosis
•□ (B) Dystrophic calcification
•□ (C) Lipofuscin deposition
•□ (D) Metastatic calcificaation
•□ (E) Fatty change
•□ (A) Amyloidosis
•□ (B) Dystrophic calcification
•□ (C) Lipofuscin deposition
•□ (D) Hemosiderosis
•□ (E) Fatty change
Case 20
• A 35-year-old woman has had headaches and abdominal pain worsening for 3 months.
There are no remarkable physical examination findings. On radionucleide scanning of the
neck, she is found to have a mass involving one of her parathyroid glands. An abdominal
CT scan suggests extensive nephrocalcinosis along with urinary tract calculi. Which of the
following laboratory test findings is most likely to accompany her disease?
• A CO2 of 30 mmol/L
• B Phosphorus of 2.2 mg/dL
• C Uric acid of 15.1 mg/dL
• D Sodium of 121 mmol/L
• E Albumin of 3.5 g/dL
• A 35-year-old woman has had headaches and abdominal pain worsening for 3 months.
There are no remarkable physical examination findings. On radionucleide scanning of the
neck, she is found to have a mass involving one of her parathyroid glands. An abdominal
CT scan suggests extensive nephrocalcinosis along with urinary tract calculi. Which of the
following laboratory test findings is most likely to accompany her disease?
• A CO2 of 30 mmol/L
• B Phosphorus of 2.2 mg/dL
• C Uric acid of 15.1 mg/dL
• D Sodium of 121 mmol/L
• E Albumin of 3.5 g/dL
• Dystrophic vs Metastatic clacification :
1- Ca deposition?
2- Extent?
3-Etiology?
4- Serum Ca level?
Intracellular accumulation
• Defenetion:

• General pathways for intracellular accumulation:

• Examples of intracellular accumulation:

• A 69-year-old woman has had transient ischemic attacks for the past
3 months. On physical examination, she has an audible bruit on
auscultation of the neck. A right carotid endarterectomy is
performed. The curetted atheromatous plaque has a grossly yellow-
tan, firm appearance. Microscopically, which of the following
materials can be found in abundance in the form of crystals that
produce long, cleft-like spaces?
•□ (A) Glycogen
•□ (B) Lipofuscin
•□ (C) Hemosiderin
•□ (D) Immunoglobulin
•□ (E) Cholesterol
•□ (A) Glycogen
•□ (B) Lipofuscin
•□ (C) Hemosiderin
•□ (D) Immunoglobulin
•□ (E) Cholesterol
Hepatic steatosis
Steatohepatitis
 Pigments
• Exogenous:

• Endogenous: lipofuscin, melanin and hemosiderin

• A 79-year-old homeless man is brought to the emergency department
by ambulance 30 minutes after being found unresponsive by the
police. On arrival, he is apneic and there are no palpable pulses.
Despite appropriate life-saving measures, he dies. Examination of the
heart during autopsy shows normal ventricles with a sigmoid-
shaped interventricular septum. A photomicrograph of a section of
the heart obtained at autopsy is shown. Which of the following is the
most likely underlying cause for the structure indicated by the arrow?
• Accumulation of iron granules
• Clumping of defective mitochondria
• Oxidation of phospholipid molecules
• Aggregation of alpha-synuclein
• Deposition of wild-type transthyretin
• Accumulation of iron granules
• Clumping of defective mitochondria
• Oxidation of phospholipid molecules
• Aggregation of alpha-synuclein
• Deposition of wild-type transthyretin
 Hemosiderin

Hemosiderin in liver cells Prussian blue reaction

85
Histopathology
Liver
Heart
Heart- normal
Heart- necrosis
Lung
Retroperitoneal fat
Retroperitoneal fat