Pathology is a science dealing with the study of diseases. Four important components of pathology are etiology (causative factors), pathogenesis (mechanism or process by which disease develops), morphology (appearance of cells, tissues or organs) and clinical features. Show CELL INJURY Disease occurs due to alteration of the functions of tissues or cells at the microscopic level. The various causes of cell injury include:
Clinical Importance In response to injury, a cell/tissue can have following consequences:
2
All the features discussed above are of reversible cell injury because if the injurious agent is removed at this point, cell can recover back to its normal state of functioning. However, if the stimulus continues, then irreversible cell injury ensues.
3 Irreversible cell injury may be necrosis or apoptosis (Programmed cell death)
4 APOPTOSIS Apoptosis or programmed cell death can be induced by intrinsic or extrinsic pathway. Normally, growth factors bind to their receptors in the cells and prevent the release of cytochrome C and SMAC. So, withdrawal or absence of growth factors can result in release of these mediators and initiate the intrinsic pathway. Intrinsic pathway: It is initiated by the release of cytochrome C and SMAC (second mitochondrial activator of caspases) from the mitochondrial inter-membrane space. Upon release into the cytoplasm, cytochrome C associates with dATP, procaspase-9 and APAF-1 (apoptosis activating factor -1) leading to sequential activation of caspase-9 and effector caspases {Caspases- 3 and -7}. On the other hand, upon release, SMAC binds and blocks the function of IAPs (Inhibitor of Apoptosis Proteins). Normally, IAPs are responsible for causing the blocking the activation of caspases and keep cells alive and so, neutralization of IAPs permits the initiation of a caspase cascade. Extrinsic pathway: It is activated by binding of Fas ligand to CD95 (Fas; member of TNF receptor family) or binding of TRAIL (TNF related apoptosis inducing ligand) to death receptors DR4 and DR5. This induces the association of FADD (Fas- associated death domain) and procaspase-8 to death domain motifs of the receptors resulting in activation of caspase 8 (in humans caspase 10) which finally activates caspases- 3 and 7 that are final effector caspases. Cellular proteins particularly a caspase antagonist called FLIP, binds to procaspase-8 but can not activate it. This is important because some viruses produce homologues of FLIP and protect themselves from Fas mediated apoptosis. 5 REGULATION OF APOPTOSIS Regulation is primarily by bcl-2 family of genes located on chromosome 18. Some members of this family like bak, bid, bin, bcl-xS (to remember, S for stimulate apoptosis) stimulate apoptosis whereas others like bcl-2, bcl-xL (to remember, L for lower apoptosis) etc inhibit apoptosis. Normal cells have bcl-2 and bcl-xL present in the mitochondrial membrane. They inhibit apoptosis because their protein products prevent the leakage of mitochondrial cyt ‘c’ into the cytoplasm. When there is absence of growth factors or hormones, bcl-2 and bcl-xL are replaced by bax, bin etc. resulting in increased permeability of mitochondrial membrane. This result in stimulation of intrinsic pathway of apoptosis (described above in flowchart). EXAMPLES OF APOPTOSIS
INTRACELLULAR ACCUMULATIONS Various substances like proteins, lipids, pigments, calcium etc. can accumulate in cells.
Disorders with protein defects
REPERFUSION INJURY It is seen with cerebral or myocardial injury. On re-establishment of blood flow, there is increased recruitment of white blood cells which cause inflammation as well as generation of more free radicals. CELLULAR AGEING Features of ageing include decreased oxidative phosphorylation, decreased synthesis of nucleic acids and proteins, deposition of lipofuscin, accumulation of glycosylation products and abnormally folded proteins. The most effective way to prolong life is calories restriction because of a family of proteins called SIRTUINS. The latter have histone deacetylase activity and promote expression of genes whose products increase longevity.
FREE RADICAL INJURY Free radical injury is caused by the following mechanisms:
Mechanism of Free Radical Injury It can result in lipid peroxidation, DNA breaks and fragmentation of the proteins. This is associated with formation of more free radicals thereby making free radical induced injury as an autocatalytic reaction.9 Antioxidants Antioxidants may act by inhibiting the generation of free radials or scavenging the already present free radicals. These may be divided into enzymatic and non-enzymatic.
CHEMICAL FIXATIVES
Commonly Used Stains
10 MULTIPLE CHOICE QUESTIONS CELL INJURY, NECROSIS, APOPTOSIS 1. CD 95 is a marker of (AIIMS Nov 2012)
2. Which of the following is the characteristic of irreversible injury on electron microscopy? (AIIMS May 2012)
3. Caspases are associated with which of the following? (AIIMS May 2010)
4. Caspases are seen in which of the following? (AI 2010)
5. Light microscopic characteristic feature of apoptosis is: (AI 2010)
6. Coagulative necrosis is found in which infection? (AI 2009, AIIMS May’ 10)
7. Organelle which plays a pivotal role in apoptosis is: (AI 2011, 09, AIIMS May 2010)
8. All of the following statements are true regarding reversible cell injury, except (AI 2005)
9. Fibrinoid necrosis may be observed in all of the following, except: (AI 2005)
10. In apoptosis, Apaf-I is activated by release of which of the following substances from the mitochondria? (AI 2005)
11. Which of the following is an anti-apoptotic gene? (AI 2004)
12. Annexin V on non-permeable cell is indicative of: (AIIMS May 2009)
13. Ultra-structural finding of irreversible injury (AIIMS Nov 2007)
14. Caspases are involved in (AIIMS Nov 2007)
15. True about Apoptosis are all except: (AIIMS May 2007)
16. The following is an antiapoptotic gene (AIIMS Nov 2006)
17. Cytosolic cytochrome C plays an important function in (AIIMS Nov 2006)
18. Most pathognomic sign of irreversible cell injury (AIIMS Nov 2006)
19. Internucleosomal cleavage of DNA is characteristic of (AIIMS Nov 2005)
20. Programmed cell death is known as: (AIIMS Nov 2005)
21. Ladder pattern of DNA electrophoresis in apoptosis is caused by the action of the following enzyme: (AIIMS Nov 2004)
22. Which finding on electron microscopy indicates irreversible cell injury? (AIIMS Nov 2002)
23. True about apoptosis is all, except: (AIIMS Nov 2001)
24. Morphological changes of apoptosis include (PGI Dec 01)
25. True about apoptosis (PGI June 2003)
26. Which of the following is the hallmark of programmed cell death? (Delhi PG 2009 RP)
27. Which of the following is an inhibitor of apoptosis? (Delhi PG-2006)
28. Inhibitor of apoptosis is: (Delhi PG-2005, DNB-2007)
29. Apoptosis is associated with all of the following features except: (Karnataka 2009)
30. Liquefactive necrosis is typically seen in (Karnataka 2006)
31. All of the following are morphological features of apoptosis except (Karnataka 2004)
32. Coagulative necrosis as a primary event is most often seen in all except: (AP 2002)
33. Liquefactive necrosis is seen in:
34. Irreversible injury in cell is (UP 2000)
35. Apoptosis is (UP-98, 2004)
36. Pyogenic infection and brain infarction are associated with (UP 2008)
37. In apoptosis initiation: (UP 2008)
38. Apoptosis is alternatively called as (RJ 2005)
39. First cellular change in hypoxia: (Kolkata 2003)
40. About apoptosis, true statement is: (Bihar 2003)
41. Fournier's gangrene is seen in: (Jharkhand 2006)
42. Coagulative necrosis is seen in: (Jharkhand 2006)
43. A patient Fahim presents to the hospital with jaundice, right upper quadrant pain and fatigue. He tests positive for hepatitis B surface antigen. The serum bilirubin levels is 4.8mg/dl (direct is 0.8mg/dl and indirect bilirubin is 4.0mg/dl), AST levels is 300 U/L, ALT is 325 U/L and alkaline phosphatase is within normal limits. The elevation in AST and ALT can be explained by which of the following?
44. A 23-year-old lady Sweety was driving her car when she had to apply brakes suddenly. She suffered from “steering wheel” injury in the right breast. After 5 days of pain and tenderness at the site of trauma, she noticed the presence “lump” which was persistent since the day of trauma. Dr. M. Spartan does an excision biopsy and observed the presence of an amorphous basophilic material within the mass. The amorphous material is an example of
45. A patient Subbu is diagnosed with a cancer. It was observed that he shows a poor response to a commonly used anti-cancer drug which acts by increasing programmed cell death. Inactivation of which of the following molecules/genes is responsible for the resistance shown in the tumor cells?
46. Dr Maalu Gupta is carrying out an experiment in which a genetic mutation decreased the cell survival of a cell culture line. These cells have clumping of the nuclear chromatin and reduced size as compared to normal cells. Which of the following is the most likely involved gene in the above described situation?
47-49. …Read the following statement for questions 49, 50 and 51 carefully and answer the associated questions. A 50-year old male Braj Singh presented to the medicine emergency room with retrosternal chest pain of 15 minutes duration. He also had sweating and mild dyspnea. The physician immediately gave him a nitrate tablet to be kept sublingually following which his chest pain decreased significantly. 47. Which of the following best represents the biochemical change in the myocardial cells of this patient during the transient hypoxia?
48. Which of the following if accumulated is suggestive of reversible cell injury due to hypoperfusion of different organs during this duration of myocardial ischemia?
49. If we presume that the patient has experienced several similar episodes of pain over the last 10 hours, which of the following ultra-structural changes would most likely indicate irreversible myocardial cell injury in this patient?
50. A 55-year-old man, Vikas develops a thrombus in his left anterior descending coronary artery. The area of myocardium supplied by this vessel is irreversibly injured. The thrombus is destroyed by the infusion of streptokinase, which is a plasminogen activator, and the injured area is reperfused. The patient, however, develops an arrhythmia and dies. An electron microscopic (EM) picture taken of the irreversibly injured myocardium reveals the presence of large, dark, irregular amorphic densities within mitochondria. What are these abnormal structures?
51. Which one of the listed statements best describes the mechanism through which Fas(CD95) initiates apoptosis?
Most Recent Questions CELLULAR ADAPTATION, INTRACELLULAR ACCUMULATION 53. Psammoma bodies are seen in all except: (AI 2011,09)
14 54. True about metastatic calcification is (AIIMS May 2009)
55. Both hyperplasia and hypertrophy are seen in? (AIIMS May 2009)
56. Which of the following is not a common site for metastatic calcification? (AIIMS Nov 2005)
57. Calcification of soft tissues without any disturbance of calcium metabolism is called (AIIMS Nov 2004)
58. The light brown perinuclear pigment seen on H & E staining of the cardiac muscle fibres in the grossly normal appearing heart of an 83 year old man at autopsy is due to deposition as: (AIIMS May 2003)
59. Dystrophic calcification is seen in: (AIIMS Nov 2002)
60. The Fenton reaction leads to free radical generation when: (AIIMS Nov 2002)
61. Mallory hyaline is seen in: (PGI Dec 2000)
62. Heterotopic calcification occurs in: (PGI Dec 2000)
63. Pigmentation in the liver is caused by all except: (PGI Dec 01)
64. Wear and tear pigment in the body refers to (Karnataka 2006)
65. Mallory hyaline bodies are seen all Except: (AI 97) (UP 2004)
66. “Russell's body” are accumulations of: (UP 2006)
67. Dystrophic calcification is seen in: (UP 2006)
68. Brown atrophy is due to (AP 2000)
69. Psammoma bodies are typically associated with all of the following neoplasms except (AP 2001)
70. Transformation of one epithelium to other epithelium is known as (AP 2001)
71. All are true about metaplasia except (AP 2004) (AIIMS 1996, UP 2002)
72. About hyperplasia, which of the following statement is false? (AP 2007)
73. Example of hypertrophy is: (Kolkata 2004)
74. Metastatic calcification occurs in all except: (Bihar 2005)
75. Dystrophic calcification is: (Jharkhand 2006)
76. An old man Muthoot has difficulty in urination associated with increased urge and frequency. He has to get up several times in night to relieve himself. There is no history of any burning micturition and lower back pain. On rectal examination, he has enlarged prostate. Which of the following represents the most likely change in the bladder of this patient?
77. An increase in the size of a cell in response to stress is called as hypertrophy. Which of the following does not represent the example of smooth muscle hypertrophy as an adaptive response to the relevant situation?
78. A patient Ramu Kaka presented with complaints of slow progressive breathlessness, redness in the eyes and skin lesions. His chest X ray had bilateral hilar lymphadenopathy. His serum ACE levels were elevated. On doing Kveim test, it came out to be positive. Final confirmation was done with a biopsy which demonstrated presence of non-caseous granuloma. A diagnosis of sarcoidosis was established. Which of the following statements regarding calcification and sarcoidosis is not true?
79. A 50-year-old male alcoholic, Rajesh presents with symptoms of liver disease and is found to have mildly elevated liver enzymes. A liver biopsy examined with a routine hematoxylin and eosin (H & E) stain reveals abnormal clear spaces in the cytoplasm of most of the hepatocytes. Which of the following materials is most likely forming cytoplasm spaces?
80. A 36-year-old woman, Geeta presents with intermittent pelvic pain. Physical examination reveals a 3-cm mass in the area of her right ovary. Histologic sections from this ovarian mass reveal a papillary tumor with multiple, scattered small, round, laminated calcifications. Which of the following is the basic defect producing these abnormal structures?
81. A 28-year-old male executive presents to the doctor with complaints of “heartburn” non responsive to usual medicines undergoes endoscopy with biopsy of the distal esophagus is taken. What type of mucosa is normal for the distal esophagus?
Most Recent Questions MISCELLANEOUS: FREE RADICAL INJURY: STAINS 83. Which of the following is the most common fixative used in electron microscopy? (AIIMS Nov 2012)
84. The fixative used in histopathology: (AIIMS May 2012)
85. Which is the most commonly used fixative in histopathological specimens? (AI 2011)
86. Lipid in the tissue is detected by: (AIIMS Nov 2009)
87. The most abundant glycoprotein present in basement membrane is: (AI 2004)
88. Enzyme that protects the brain from free radical injury is: (AI 2001)
89. Increased incidence of cancer in old age is due to (AIIMS May 2009)
90. Stain not used for lipid (AIIMS Nov 2007)
91. Acridine orange is a fluorescent dye used to bind (AIIMS Nov 2007)
92. PAS stains the following except (AIIMS Nov 2007)
93. All are components of basement membrane except (AIIMS Nov 2007)
94. Which of the following pigments are involved in free radical injury? (AIIMS Nov 2006)
95. True about cell ageing: (AIIMS Nov 2001)
96. Neutrophil secretes: (PGI Dec 2002)
97. Which of the following is a peroxisomal free radical scavenger? (Delhi PG 2006)
98. Crooke's hyaline body is present in: (Kolkata 2001)
99. An autopsy is performed on a 65-year-old man, Suresh who died of congestive heart failure. Sections of the liver reveal yellow-brown granules in the cytoplasm of most of the hepatocytes. Which of the following stains would be most useful to demonstrate with positive staining that these yellow-brown cytoplasmic granules are in fact composed of hemosiderin (iron)?
100. An AIDS patient Khalil develops symptoms of pneumonia, and Pneumocystis carinii is suspected as the causative organism. Bronchial lavage is performed. Which of the following stains would be most helpful in demonstrating the organism's cysts on slides made from the lavage fluid?
101. Which process makes the bacteria ‘tasty’ to the macrophages: (Kolkata 2008)
102. In an evaluation of a 7-year-old boy, Ram who has had recurrent infections since the first year of life, findings include enlargement of the liver and spleen, lymph node inflammation, and a superficial dermatitis resembling eczema. Microscopic examination of a series of peripheral blood smears taken during the course of a staphylococcal infection indicates that the bactericidal capacity of the boy's neutrophils is impaired or absent. Which of the following is the most likely cause of this child's illness?
Most Recent Questions EXPLANATIONS 1. 18 Ans. (b) Extrinsic pathway of apoptosis (Ref: Robbins 8/e p29-30, 9/e p56) In the activation of Extrinsic pathway of apoptosis, binding of Fas ligand takes place to CD95 (Fas; member of TNF receptor family) or binding of TRAIL (TNF related apoptosis inducing ligand) attaches to death receptors DR4 and DR5. This induces the association of FADD (Fas- associated death domain) and procaspase-8 to death domain motifs of the receptors resulting in activation of caspase 8 (in humans caspase 10) which finally activates caspases- 3 and 7 that are final effector caspases 2. Ans. (b) Amorphous densities in mitochondria (Ref: Robbins 8/e p14-19, 9/e p42,50) Two phenomena consistently characterize irreversibility:
So, the answer for the given question is ‘Amorphous densities in mitochondria’. However, please remember friends that the Robbins in its 8th edition pg 14 mentions small amorphous densities to be present in reversible cell injury also. Therefore, the best answer for characterizing irreversibility of an injury is ‘profound disturbances in membrane function’. 3. Ans. (c) Embryogenesis (Ref: Robbins 8/e p25, 9/e p52) Caspases are cysteine proteases and are critical for the process of apoptosis. Physiologically, apoptosis is required to eliminate the cells no longer required and to maintain a steady number of various cell populations in tissues. The programmed cell death (apoptosis) is required at the time of different processes in embryogenesis like implantation, organogenesis, developmental involution and metamorphosis. 4. Ans. (b) Apoptosis (Ref: Robbins 8/e p27, 9/e p53) 5. Ans. (d) Condensation of the nucleus (Ref: Robbins 8/e p14-15, 26-27, 9/e p53) The morphologic features characteristic of apoptosis includes
Regarding option ‘a’…’Plasma membranes are thought to remain intact till late stage of apoptosis, as well as is a normal cell. Regarding option “b”, eosinophilic cytoplasm, it is a common feature of necrosis and apoptosis. 6. Ans. (a) TB > (c) Gangrene (Ref: Robbins 8/e p16, 9/e p43) In the 7th edition of Robbins it was clearly stated that…“Caseous necrosis, a distinctive form of coagulative necrosis, is encountered most often in foci of tuberculous infection. The term caseous is derived from the cheesy white gross appearance of the area of necrosis.” Regarding the option gangrene, it is not specified the type of gangrene and therefore, we go with the better option as tuberculosis in the given question. Moreover, according to Robbins, gangrenous necrosis is not a specific pattern of necrosis but is a term used in clinical practice. 7. Ans. (c) Mitochondria (Ref: Robbins 8/e p28, Harrison 18/e p681, 9/e p53) 8. Ans. (a) Formation of Amorphous densities in mitochondrial matrix (Ref: Robbins 7/e p19, 9/e p42)
Formation of amorphous densities in the mitochondrial matrix is a feature of irreversible injury and not reversible injury.
19
9. Ans. (c) Diabetic glomerulosclerosis (Ref: Robbins 7/e p214, 594, 1008, 9/e p44) Fibrinoid necrosis is a distinctive morphological pattern of cell injury characterized by deposition of fibrin like proteinaceous material in walls of arteries. Areas of fibrinoid necrosis appear as smudgy eosinophilic regions with obscured underlying cellular details. Fibrinoid necrosis is seen in
10. Ans. (d) Cytochrome C (Ref: Robbins 7/e p30; Harrison 17/e p506, 9/e p55) Apoptosis or programmed cell death can be induced by intrinsic or extrinsic pathway. As can be seen in the intrinsic pathway; cyt c gets associated with APAF-1 which activates caspase and cause cell death. For detail see text. 11. Ans. (c) bcl – 2 (Ref: Robbins 7/e p29-30, Harrison 17/e p506) 12. Ans. (a) Apoptosis (Ref: Robbins 8/e p27, 9/e p56) Apoptotic cells express phosphatidylserine in the outer layers of their plasma membranes. This phospholipid moves out from the inner layers where it is recognized by a number of receptors on the phagocytes. These lipids are also detected by binding of a protein called Annexin V. So, Annexin V staining is used to identify the apoptotic cells. 13. Ans. (b) Amorphous densities in mitochondria (Ref: Robbins 7/e p12, 9/e p42) See earlier explanation. 14. Ans. (b) Apoptosis (Ref: Robbins 7/e p28, 9/e p53) Caspases are present in normal cells as inactive proenzymes and when they are activated they cleave proteins and induce apoptosis. These are cysteine proteases. 15. Ans. (a) Inflammation is present (Ref: Robbins 7/e p31, 27, 9/e p56) In Apoptosis the dead cell is rapidly cleared, before its contents have leaked out, and therefore cell death by this pathway does not elicit an inflammatory reactionQ in the host. 16. Ans. (c) Bcl-X (Ref: Robbins 7/e p29, 9/e p55) 17. Ans. (a) Apoptosis (Ref: Robbins 7/e p26, 9/e p55) 18. Ans. (a) Amorphous densities in mitochondria (Ref: Robbin's 7/e p12, 9/e p50) Two phenomenon's consistently characterize irreversible cell injury:
19. Ans. (d) Apoptosis (Ref: Robbin's 7/e p27; Robbins 8/e p27, 9/e p52) The inter-nucleosomal cleavage of DNA into oligonucleosomes (in multiples of 180-200 base pairs) is brought about by Ca2+ and Mg2+ dependent endonucleases and is characteristic of apoptosis. 20. Ans. (b) Apoptosis (Ref: Robbins 7/e p26, 27, 9/e p52) 21. Ans. (a) Endonuclease (Ref: Robbins 7/e p26, 27, 28; 8/e pg28)
22. 20 Ans. (c) Flocculent densities in mitochondria (Ref: Robbins's 7/e p12, 9/e p50) 23. Ans. (c) Apoptosis of cells induce inflammatory reaction (Ref: Robbins 7/e p27, 9/e p56) Remember important features of apoptosis 24. Ans. (a) Cytoplasmic blebs; (c) Nuclear Fragmentation: (Ref: Robbins 7/e p26, 9/e p53) Apoptosis is a programmed cell death. During apoptosis, cells destined to die activate enzymes that degrade the cell's own nuclear DNA and nuclear and cytoplasmic proteins. There is no inflammatory reaction elicited by host.
25. Ans. (b) End products are phagocytosed by macrophage; (c) Intranuclear fragmentation of DNA; (d) Activation of caspases; (e) Annexin V is a marker of apoptotic cell (Ref: Harsh Mohan 5th/53, Robbins 7/e p25-3l, 9/e p53) 26. Ans. (a) Apoptosis (Ref: Robbins 8/e p25, 9/e p52) 27. Ans. (c) Bcl-2 (Ref: Robbins 7/e p31, 32)
28. Ans. (d) Bcl-2 (Ref: Robbins 7/e p29, 31, 32, 9/e p55) 29. Ans. (c) Inflammation (Ref: Robbins 7/e p26, 9/e p53) 30. Ans. (b) Ischemic necrosis of the brain (Ref: Robbins 7/e p21-22, 9/e p43) 31. Ans. (c) Inflammation (Ref: Robbin 7/e p27, 9/e p56) 32. Ans. (b) CNS (Ref: Robbins 8/e p15, 7/e p22, 9/e p43) 33. Ans. (b) Brain (Ref: Robbins 8/e p15, 7/e p22, 9/e p43) 34. Ans. (a) Deposition of Ca++ in mitochondria (Ref: Robbins 8/e p13-14; 7/e p11, 9/e p47) 35. Ans. (b) Type of cell injury (Ref: Robbins 8/e p25; 7/e p26-28, 9/e p52) 21 36. Ans. (b) Liquefactive necrosis (Ref: Robbins 7/e p22, 8/e p1300, 9/e p43) 37. Ans. (a) The death receptors induce apoptosis when it engaged by fas ligand system (Ref: Robbins 8/e p29; 7/e p30, 9/e p56) 38. Ans. (b) Programmed cell death (Ref: Robbins 8/e p25, 9/e p52) 39. Ans. (a) Decreased oxidative phosphorylation in mitochondria (Ref: Robbins 8/e p18-19, 7/e p15, 9/e p45) 40. Ans. (c) Councilman bodies is a type of apoptosis (Ref: Robbins 8/e p25; 7/e 26, 9/e p823) 41. Ans. (b) Scrotal skin 42. Ans. (c) Liver (Ref: Robbins 7/e p21, 8/e p15; 9/e p43) 43. Ans. (b) Cell membrane rupture (Ref: Robbins 8/e p23, 9/e p49-50) The symptoms and the medical reports of the patient are suggestive of liver cell injury. Out of the options provided, rupture of the cell membrane is the only cellular change suggestive of irreversible cell injury. All others may be seen in reversible cell injury as well. 44. Ans. (b) Dystrophic fat necrosis (Ref: Robbins 8/e p16-17, 9/e p65) The situation described above is a typical description of a traumatic fat necrosis. This condition needs to be distinguished from enzymatic fat necrosis. The hint is in the stem of the question which describes the presence of amorphous basophilic material. This is suggestive of calcification and such pattern of calcification of previous damaged tissue is termed dystrophic calcification. 45. Ans. (c) p53 (Ref: Robbins 8/e p30,292, 9/e p53-55) When anti-cancer drugs are administered, they induce the death of the tumor cells by activating p53 gene and increasing apoptosis. Tumor cells may show resistance to these drugs if there is a mutation in the p53 gene thereby preventing apoptosis. Bcl-2 promotes the cell growth by inhibiting apoptosis. Granzyme and perforin also increase apoptosis but in case of cytotoxic T cells. Cytochrome P450 is not associated with apoptosis. 46. Ans. (c) Bcl-2 (Ref: Robbins 8/e p28, 9/e p55) The process being described in the stem of the question is apoptosis. Fas and Bax are genes which promote apoptosis. Bcl-2 is inhibitory for apoptosis. So, a Bcl-2 mutation is associated with an increase in apoptosis. Myc is involved in development of cancer and not directly associated with apoptosis. 47. Ans. (d) Stimulation of anaerobic glycolysis and glycogenolysis (Ref: Robbins 8/e p18, 9/e p46) The hypoxic cell damage results in decrease in oxidative phosphorylation followed by ATP depletion and increase in AMP and ADP. Increased phosphofructokinase and phosphorylase activities respectively stimulate anaerobic glycolysis and glycogenolysis. This results in decrease in intracellular pH and depletion of cellular glycogen stores. Decrease availability of ATP also results in failure of the Na+ -K+- ATPase pump, which then leads to increased cell Na+ and water and decreased cell K+. 48. Ans. (c) Lactic acid (Ref: Robbins 8/e p18, 9/e p45) Anaerobic glycolysis results in accumulation of cellular lactic acid in almost every organ having reduced perfusion. Lactate accumulation also causes reduced pH. Carbon dioxide and creatinine would increase in involvement of the lung and the kidneys respectively. But these are not common for every organ involvement. 49. Ans. (c) Mitochondrial vacuolization (Ref: Robbins 8/e p19, 9/e p46) The appearance of vacuoles and phospholipid-containing amorphous densities within mitochondria generally signifies irreversible injury, and implies a permanent inability to generate further ATP via oxidative phosphorylation. When the mitochondria are injured irreversibly, the cell cannot recover. 50. 22 Ans. (b) Flocculent densities (Ref: Robbins 7/e p15-16, 37-38, , 9/e p51)
51. Ans. (c) i.e. FADD stimulates caspase – 8 (Ref: Robbins 7/e p26-32, , 9/e p56)
52.1. Ans. (a) Apaf 1 (Ref: Robbins 8/e p29, 9/e p55) On being released in the cytosol,cytochromecbinds to a protein called Apaf-1 (apoptosis-activating factor-1 which is responsible for formation of a complex called apoptosome. This complex binds to caspase-9 which is a critical initiator caspase of the mitochondrial pathway of apoptosis. NEET POINTS about APOPTOSIS
52.2. Ans. (b) Neurons (Ref: Robbins 8/e p11-2)
52.3. Ans. (b) Cell membrane (Ref: Robbins 8/e p23, 9/e p50-51) Dead cells may be replaced by large, whorled phospholipid masses called myelin figures that are derived from damaged cell membranes. These phospholipid precipitates are then either phagocytosed by other cells or further degraded into fatty acids. 52.4. Ans. (a) Mitochondrial densities (Ref: Robbins 8/e p23-4, 9/e p50) The two key features of irreversible injury are:
52.5. Ans. (b) CNS (Ref: Robbins 8/e p15, 7/e p22, 9/e p43) As discussed in text, central nervous system is characterized by the presence of liquefactive necrosisQ during ischemic injury. 52.6. Ans. (b) Brain (Ref: Robbins 8/e p15, 7/e p22, 9/e p43) As discussed earlier, CNS shows liquefactive necrosis. 52.7. Ans. (c) Mitochondria (Ref: Robbins 8/e p28, 7/e p29, 9/e p15, 53) Mitochondrion must be recognized not only as an organelle with vital roles in intermediary metabolism and oxidative phosphorylation, but also as a central regulatory structure of apoptosis. 52.8. Ans. (a) Mitochondria (Ref: Robbins 8/e p19, 9/e p65-66) Direct quote.. “Initiation of intracellular calcification occurs in the mitochondria of dead or dying cells that accumulate calcium”. 23 52.9 Ans. (d) Glucocorticoids (Ref: Underwood's Pathology 6/e p80) Glucocorticoids induce apoptosis while sex steroids inhibit apoptosis… Underwood Pathology
52.10. Ans. (c) Inflammation (Ref: Robbin 8/e p26-7) Inflammation is not seen in apoptosis. Chromatin condensation is the most characteristic feature of apoptosis. Other findings like cell membrane shrinkage and DNA fragmentation are also associated with apoptosis. 52.11. Ans (a) Bcl-2 (Ref: Robbin 9th/ 8thed: pg606) We need to identify a gene which should be able to inhibit apoptosis. The answer therefore is bcl-2. It is seen to result in the development of follicular lymphoma. 52.12. Ans (b) Both may be pathological (Ref: Robbin 9th/40) 53. Ans. (a) Follicular carcinoma of Thyroid (Ref: Robbins 8/e p38, 9/e p65) Tumors (MOST for PG)
(Psammoma bodies are seen in papillary thyroid cancer and not follicular thyroid cancer) 54. Ans. (d) Mitochondria involved earliest (Ref: Robbins 8/e p38, Robbins 7/e p41-42, 9/e p65)
Friends, Robbins 7th edn page 41-42 mentions that initiation of intracellular calcification occurs in the mitochondria of dead or dying cells that accumulate calcium. Nothing is mentioned regarding the involvement of mitochondria in metastatic calcification in either 8th or 7th edition of Robbins. However, we got an article on Medscape which states that “Within the cell it is the mitochondria that serves as the nidus for metastatic calcification”. 55. Ans. (b) Uterus during pregnancy (Ref: Robbins 8/e p6-8, 9/e p36)
56. Ans. (c) Parathyroid (Ref: Robbins 7/e p42, 9/e p65)
57. Ans. (c) Dystrophic calcification (Ref: Robbins 7/e p41, 8/e p38, 9/e p65) 58. Ans. (b) Lipochrome (Ref: Robbins 7/e p39, 9/e p64) Regarding other options
59. Ans. (c) Atheromatous plaque (Ref: Robbins 7/e p41, 9/e p65)
60. Ans. (c) Ferrous ions are converted to ferric ions (Ref: Robbins’ 7/e p16, 9/e p48)
61. Ans. (a) Alcoholic liver disease; (b) Hepatocellular carcinoma; (c) Wilson's disease; (d) I.C.C. (Indian childhood cirrhosis); (e) Biliary cirrhosis (Ref: Robbins’ 7/e p905) Mallory bodies: Scattered hepatocytes accumulate tangled skeins of cytokeratin intermediate filaments and other proteins, visible as eosinophilic cytoplasmic inclusions in degenerating hepatocytes. See details in chapter on ‘Liver’. 62. Ans. (a) Ankylosing spondylitis; (c) Forrestier's disease (Ref: Robbins’ 7/e p41-2; Harrison17/e p1952) Pathologic calcification (Heterotopic calcification) is the abnormal tissue deposition of calcium salts together with small amounts of iron, manganese and other mineral salts. It may be of two types: Dystrophic calcification or Metastatic calcification 63. Ans. None (Ref: Harsh Mohan 5th/735; Robbins 7/e p39, 910, 914) Pigmentation in liver is caused by:
64. Ans. (a) Lipochrome (Ref: Robbins 7/e p39, 9/e p64) 65. Ans. (d) Crigler-Najjar syndrome (Ref: Robbins 8/e p858; 7/e p905, Harsh Mohan 6/e p621-622) 66. Ans. (b) Immunoglobulins (Ref: Robbins 8/e p610; 7/e p680-681, 9/e p63) 67. Ans. (a) Atheroma (Ref: Robbins 8/e p38, 7/e p41-42, 9/e p65) 68. Ans. (c) Lipofuscin (Ref: Robbins 8/e p10,532; 7/e 10, 9/e p64) 69. Ans. (a) Medulloblastoma (Ref: Robbins 8/e p38, 1122; 7/e 41,1178,1407, 9/e p65) 25 70. Ans. (d) Metaplasia (Ref: Robbins 8/e p10,11; 7/e 10,11, 9/e p37) 71. Ans. (c) Irreversible (Ref: Robbins 8/e p265; 7/e 10), 9/e p37-38 72. Ans. (b) ↑ Size of affected cell (Ref: Robbins 8/e p8-9, 7/e p7 , 9/e p35) 73. Ans. (b) Uterus during pregnancy (Ref: Robbins 8/e p6, 7/e p7-8 , 9/e p34-36) 74. Ans. (b) Atheroma (Ref: Robbins 8/e p38; 7/e p41, 9/e p65) 75. Ans. (a) Calcification in dead tissue (Ref: Robbins 8/e p38, 7/e p41, 9/e p65) 76. Ans. (c) Hypertrophy (Ref: Robbins 8/e p6-7, 9/e p36) The patient is most likely suffering from benign hyperplasia of the prostate. The question however asks about the change in bladder which would be hypertrophy. This is secondary to the obstruction in the urine outflow following the smooth muscle in the bladder undergoes hypertrophy. 77. Ans. (c) Triceps in body builders (Ref: Robbins 8/e p6-7, 9/e p34) The enlargement of the triceps is an example of skeletal muscle hypertrophy (not smooth muscle hypertrophy). 78. Ans. (b) There is presence of dystrophic calcification (Ref: Robbins 8/e p38, 9/e p65) In sarcoidosis, there is presence of metastatic calcification because of the presence of increased concentration of calcitriol (most active form of vitamin D). Both the patterns of calcification begin in mitochondria. 79. Ans. (e) Triglyceride (Ref: Robbins 7/e p35-37, 41-42; Chandrasoma, 3/8-10, 9/e p62)
80. Ans. (b) Dystrophic calcification (Ref: Robbins 7/e p41-42; Henry/195-196, 9/e p65)
81. Ans. (d) i.e. Non-keratinized, stratified, squamous epithelium (Ref: Robbins 8/e p770, 9/e p37) The esophagus is covered by non-keratinized, stratified, squamous epithelium for its entire length. Heartburn is usually a sign of gastric regurgitation of the acidic contents in the lower esophagus (acid reflux disease). 82.1. Ans. (d) Seen in teratoma (Ref: Robbins 8/e p38, 9/e p65) The progressive acquisition of outer layers may create lamellated configurations, called psammoma bodies because of their resemblance to grains of sand. Some common cancers associated with psammoma bodies are:
26 82.2. Ans. (b) Lungs (Ref: Dail and Hammar's Pulmonary Pathology: Non-neoplastic lung disease, Springer 3/e p777) Direct quote…‘Lung are the most frequent involved of all organs.’ Ours is the only and the first book to give you an authentic reference for this one friends. This is in sharp contrast to all our competitors who give name and page number of books where this info is just not there. Try that yourself. You would find many such questions and answers in other chapters of this edition. Happy reading! 82.3. Ans. (d) Plasma cells (Ref: Robbins 8/e p35, 7/e p37, 9/e p63) Russell bodies are homogenous eosinophilic inclusions that result from hugely distended endoplasmic reticulum. 82.4. Ans. (b) Dystrophic (Ref: Robbins 8/e p38, 7/e p41 , 9/e p65) Direct quote… “On occasion single necrotic cells may constitute seed crystals that become encrusted by the mineral deposits. The progressive acquisition of outer layers may create lamellated configurations, called psammoma bodies.” 82.5. Ans. (b) Ca++ (Ref: Harsh Mohan 6/e p106-107, Robbins 7/e p705) In chronic venous congestion of spleen, some of the hemorrhages overlying fibrous tissue get deposits of hemosiderin and calcium, these are called as Gamma Gandy bodies or siderofibrotic nodules. 82.6. Ans. (c) Mitochondria (Ref: Robbins 8/e p35, 7/e p37 , 9/e p53) Oncocytes are epithelial cells stuffed with mitochondria, which impart the granular appearance to the cytoplasm. 83. Ans. (a) Glutaraldehyde (Ref: Bancroft 6/e p53, Ackerman 9th/27) 84. Ans. (a) 10% buffered neutral formalin (Ref: Bancroft 6/e p53, Ackerman 9th/27)
85. Ans. (b) Formaldehyde (Ref: Bancroft 6/e p53)
86. Ans. (c) Oil Red O (Ref: Bancroft histology 6/e p53) 87. Ans. (a) Laminin (Ref: Robbins 7/e p105, Harrison 17/e p2462 , 9/e p24) Laminin is the most abundant glycoprotein in basement membranes. Type IV collagen, laminin and nidogen are present in basement membranes. 88. Ans. (b) Superoxide dismutase (Ref: Robbins 7/e p17, Harrison's 17/e p2572 , 9/e p48)
89. Ans. (a) Telomerase reactivation (Ref: Robbins 8/e p296-297 , 9/e p67) 90. Ans. (b) Congo red (Ref: Bancroft's histopathology 5th/204) Congo red is used for staining amyloid and not lipids Stains for Lipids
27 91. Ans. (a) DNA and RNA (Ref: Bancroft 5th/236, 237, 238)
92. Ans. (b) Lipids (Ref: Bancroft's histopathology 5th/204) PAS (periodic acid-Schiff) stain is versatile and has been used to stain many structures including glycogen, mucin, mucoprotein, glycoprotein, as well as fungi. PAS is useful for outlining tissue structures, basement membranes, glomeruli, blood vessels and glycogen in the liver. 93. Ans. (d) Rhodopsin (Ref: Robbins 7/e p103, 9/e p24) Basement membrane is Periodic Acid Schiff (PAS) positive amorphous structures that lie underneath epithelia of different organs and endothelial cells. It consists of
94. Ans. (a) Lipofuscin (Ref: Robbins 7/e p39 , 9/e p64) Important points about Lipochrome or Lipofuscin. 95. Ans. (c) Lipofuscin accumulation (Ref: Robbins 8/e p36, 39 – 41, 9/e p64) 96. Ans. (b) Myeloperoxidase; (e) Cathepsin G (Ref: Robbins 7/e p73)
97. Ans. (d) All of the above (Ref: Robbins 7/e p17 , 9/e p48)
98. Ans. (b) Basophil cells of the pituitary gland in Cushing's syndrome (Ref: Robbins 8/e p1149) 99. Ans. (c) Prussian blue stain (Ref: Robbins 7/e p39- 42, 9/e p64)
100. Ans. (c) i.e. Methenamine silver (Ref: Harsh Mohan 6/e p474) The appropriate stain is methenamine silver. The routine hematoxylin and eosin does not adequately demonstrate the organisms. The cysts, when stained with methenamine silver, have a characteristic cup or boat shape; the trophozoites are difficult to demonstrate without electron microscopy. 101. Ans. (c) Opsonisation (Ref: Robbins 8/e p52-53, 7/e p59 , 9/e p78) 102. Ans. (a) Defect in the enzyme NADPH oxidase (Ref: Robbins 7/e p61-62, 243-244 , 9/e p79) Patients with chronic granulomatous disease have defective functioning of phagocytic neutrophils and monocytes.
102.1. Ans. (c) Nigrosin 102.2. Ans. (c) Masson fontana stain (Ref: Histopathology p150)
102.3. Ans. (b) Causes carcinogenesis (Ref: Robbins 8/e p40, 9/e p67)
Decreased activity of telomerase is associated with ageing whereas its excessive activity is associated with cancers.29 GOLDEN POINTS FOR QUICK REVISION (CELL INJURY)
UPDATED INFORMATION FROM 9TH EDITION OF ROBBINS Necroptosis and Pyroptosis Autophagy What happens in irreversible cell injury?Irreversible responses of cell injury refer to changes that lead to a new equilibrium with the environment. Types of irreversible responses include: interruption of membrane integrity; hydrolysis of phospholipids, proteins and nucleic acids; and necrosis, where organelles undergo a sequence of changes.
What are the intracellular causes of cell injury?Oxygen deprivation, Physical agents, Chemical agents and drugs, Immunologic reactions, Infectious agents, Nutritional imbalances, Genetic derangement.
What is the most important factor in irreversible cell injury?Deficiency of oxygen and/or essential nutrients and metabolites. Cell injury can be reversible or irreversible. Hypoxia is the most important cause of cell injury. Irreversible cell injury can be recognized by changes in the appearance of the nucleus and rupture of the cell membrane.
What is the most common cause of injury to cells?Oxygen Deprivation
Extremely important common cause of cell injury/cell death. Causes include reduced blood flow (ischemia), inadequate oxygenation of the blood, decreased blood oxygen-carrying capacity.
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