General Pathology Practice Questions

Q: Caspase-1 mediated cell death with inflammation is known as

Pyroptosis. ***Pyroptosis*** - This form of programmed cell death is characterized by the formation of an **inflammasome** complex [2], activating **Caspase-1** [1]. - Caspase-1 activation leads to the cleavage of pro-IL-1$\beta$ and pro-IL-18 into their active forms, resulting in a highly **inflammatory** process and cell lysis [1]. *Necroptosis* - This programmed, but non-apoptotic, cell death is mediated by the **RIPK1/RIPK3/MLKL** signaling pathway, involving receptor-interacting protein kinases [1]. - It is morphologically similar to necrosis but can be pharmacologically inhibited; it is **Caspase-independent** [3]. *Ferroptosis* - Ferroptosis is a form of regulated necrosis driven by **iron-dependent lipid peroxidation**. - It is characterized by the accumulation of reactive oxygen species and is typically **Caspase-independent**. *Necrosis* - Necrosis is an uncontrolled, **non-programmed** form of cell death resulting from acute cellular injury or pathology (e.g., ischemia). - It involves cell swelling, rupture of the plasma membrane, and leakage of cellular contents, leading to massive local inflammation, but is **not directly mediated by Caspase-1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, p. 71. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 196. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 69-71.

Q: A middle-aged man from an endemic region presents with progressive swelling of the lower limb. A peripheral blood smear shows the following structure. What is the most likely cause of his limb swelling?

Lymphatic obstruction. ***Lymphatic obstruction*** - The image displays **microfilariae** (suggesting **Lymphatic Filariasis**), where the adult worms settle in the lymphatics, physically blocking flow. - This obstruction results in chronic, progressive edema (known as **lymphedema** or **elephantiasis**) due to the failure of lymphatic drainage in the affected limb. *Hypoalbuminemia* - Edema from **hypoalbuminemia** is due to low plasma oncotic pressure and typically results in generalized, pitting edema, which is not characteristic of chronic, localized filarial swelling. - While malnutrition might co-exist, the core pathology shown by the presence of **microfilariae** points specifically to mechanical lymphatic blockage. *Hypoproteinemia* - **Hypoproteinemia** is a general cause of edema via reduced **oncotic pressure**, leading to fluid shift into the interstitial spaces, usually causing generalized rather than localized swelling. - This systemic cause does not account for the specific parasitic damage to the lymphatics demonstrated by the presence of the **filarial worms**. *increased hydrostatic pressure* - Increased hydrostatic pressure (e.g., in conditions like DVT or CHF) leads to fluid leakage from capillaries, causing pitting edema. - The root cause here is the parasitic **destruction and obstruction of lymph nodes and channels**, which specifically impairs lymph return, not capillary hydrostatic pressure regulation.

Q: Which of the following types of cell death involves activation of caspase enzymes?

Apoptosis and Pyroptosis. ***Apoptosis and Pyroptosis*** - **Apoptosis** is the classic caspase-dependent programmed cell death pathway [1] - Involves **initiator caspases** (Caspase-8, Caspase-9) and **executioner caspases** (Caspase-3, -6, -7) - Characterized by cell shrinkage, chromatin condensation, and apoptotic body formation - **Pyroptosis** is an inflammatory form of programmed cell death that is strictly caspase-dependent [2] - Mediated by **inflammatory caspases** (Caspase-1, -4, -5, -11) [2] - Involves cleavage of Gasdermin-D leading to membrane pore formation - Triggered by inflammasome activation (particularly NLRP3) *Necrosis and Apoptosis* - **Necrosis** is caspase-independent and represents unregulated cell death from acute injury - Characterized by cell swelling, membrane rupture, and inflammatory response - Does not involve programmed activation of caspase enzymes *Apoptosis and necroptosis* - **Necroptosis** is a regulated form of necrotic cell death that occurs in a **caspase-independent** manner [2] - Executed through RIPK1-RIPK3-MLKL kinase pathway [2] - Typically occurs when caspase activity is inhibited or blocked *Apoptosis only* - Incomplete answer as **pyroptosis** is also inherently caspase-dependent - Pyroptosis uses inflammatory caspases (Caspase-1/4/5) distinct from apoptotic caspases - Both pathways represent distinct forms of caspase-mediated programmed cell death **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 64-67. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, p. 71.

Q: A 2-year-old child presents with growth retardation, pallor, bruising and has palpable spleen 5 cm below left costal margin. Bone marrow examination is shown below. Which is incorrect about the clinical diagnosis? (Recent NEET Pattern 2016-17)

Defect on chromosome 3. ***Defect on chromosome 3*** - The clinical presentation (growth retardation, pallor, bruising, massive splenomegaly) and the bone marrow image showing a **Gaucher cell** (macrophage with a characteristic "crinkled paper" or "crumpled tissue paper" cytoplasm due to glucocerebroside accumulation) are classic for **Gaucher disease**. - Gaucher disease is caused by a **deficiency of the enzyme glucocerebrosidase**, which is encoded by the GBA gene located on **chromosome 1q21**, not chromosome 3. Therefore, a defect on chromosome 3 is incorrect. *Glucosylceramide accumulation in reticulo-endothelial cells* - This is a correct feature of Gaucher disease, where the deficient enzyme **glucocerebrosidase** leads to the accumulation of its substrate, **glucocerebroside (glucosylceramide)**, primarily within macrophages (reticulo-endothelial cells). - These lipid-laden macrophages are known as **Gaucher cells** and are pathognomonic for the disease. *Bleeding episodes* - **Thrombocytopenia** (low platelet count) is a common hematological manifestation in Gaucher disease, often due to **hypersplenism** caused by massive splenomegaly and direct bone marrow infiltration. - This low platelet count can lead to an increased tendency for **bruising and bleeding episodes**, which is consistent with the patient's bruising. *Erlenmeyer flask deformity of the distal femur* - This is a characteristic **radiological finding** in Gaucher disease, particularly in the long bones. - It refers to the **widening of the distal metaphysis** of the femur, resembling an Erlenmeyer flask, due to bone marrow infiltration by Gaucher cells.

Q: A 6-month-old child presents with loss of vision and regression of milestones. On examination hepatosplenomegaly and lymphadenopathy is seen. The bone marrow aspiration shows abnormal macrophage shown below. It stains positive for fat and negative for iron. Identify the cell.

Niemann-Pick cell. ***Niemann-Pick cell*** - The image shows a macrophage with a **foamy, vacuolated cytoplasm**, which is characteristic of a Niemann-Pick cell, resulting from the accumulation of **sphingomyelin**. [1] - The clinical presentation of a 6-month-old with **loss of vision, regression of milestones, hepatosplenomegaly, and lymphadenopathy** is highly consistent with Niemann-Pick disease. [1] *Gaucher cell* - A Gaucher cell typically has a **fibrillar or "crinkled paper" cytoplasm** appearance due to the accumulation of glucocerebroside, which is different from the foamy appearance seen here. - While Gaucher disease presents with hepatosplenomegaly, **neurological regression and vision loss in infancy** are more characteristic of Niemann-Pick disease type A in this age group. *Hemosiderosis* - Hemosiderosis involves the accumulation of **iron (hemosiderin)** within macrophages, which would stain positive for iron. The question states the cells stained **negative for iron**. - Clinically, hemosiderosis is primarily characterized by organ damage due to iron overload, not neurological regression or vision loss in infancy as described. *Hallervorden Spatz disease* - Hallervorden Spatz disease (now known as pantothenate kinase-associated neurodegeneration) is a neurological disorder characterized by **iron accumulation in the basal ganglia**. - It does not primarily present with generalized macrophage abnormalities like those seen here, nor with prominent hepatosplenomegaly or lymphadenopathy and the affected cells would contain iron, not fat. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 161-162.

Q: A 50-year-old patient with family history positive for premature coronary artery disease is found to have lumps on Achilles tendon. Biopsy from the lesion shows presence of:

Touton giant cell. ***Touton giant cell*** - The clinical presentation of **Achilles tendon lumps** in a patient with **family history of premature coronary artery disease** is classic for **tendinous xanthomas** seen in familial hypercholesterolemia. - **Touton giant cells** are the characteristic histologic finding in xanthomas, featuring **multiple nuclei arranged in a ring** around a central area of **foamy, lipid-laden cytoplasm**. - These multinucleated giant cells form when macrophages fuse together in response to lipid accumulation in tissues. *Foam cell* - **Foam cells** (lipid-laden macrophages) are indeed present in xanthomas and give them their characteristic appearance. - However, they are typically **mononuclear or binuclear cells**, not the specific multinucleated giant cells with ring-like nuclear arrangement. - While foam cells are a component of xanthomas, the question asks for the most characteristic cell type found on biopsy. *Fatty streak* - A **fatty streak** is an early atherosclerotic lesion found in the **intima of arterial walls**, not in tendons. - It represents a macroscopic pathologic finding in blood vessels, consisting of aggregates of foam cells. - This would not be found in a biopsy of an Achilles tendon lump. *Langhan's giant cells* - **Langhan's giant cells** are characteristic of **chronic granulomatous inflammation**, particularly in tuberculosis and sarcoidosis. - They are formed by fusion of epithelioid macrophages with nuclei arranged in a **horseshoe or peripheral pattern**, not the central ring pattern of Touton cells. - These cells are associated with cell-mediated immune responses to infections or foreign material, not lipid storage disorders.

Q: Agarose gel electrophoresis from DNA of a population of cells as seen under ultraviolet light is shown below. What is the correct explanation for the finding seen in the band labeled as "C"?

Apoptotic cells. ***Apoptotic cells*** - Band C shows a characteristic **DNA ladder pattern** with discrete bands representing fragmentation into nucleosome-sized units (multiples of ~180-200 base pairs), which is pathognomonic of **apoptosis**. [1] - During apoptosis, **endonucleases** cleave DNA at internucleosomal linker regions, creating uniform fragments that migrate as distinct bands on agarose gel electrophoresis. *Predominantly necrotic cells* - **Necrotic cell DNA** undergoes random, non-specific degradation by cellular enzymes, resulting in a continuous **smear pattern** rather than discrete bands. - The **smear appearance** reflects DNA fragments of varying sizes distributed throughout the gel, unlike the organized pattern seen in band C. *Mixed population of normal and apoptotic cells* - A mixed population would show both **intact high molecular weight DNA** (remaining near the gel origin) and the **apoptotic ladder pattern** superimposed. - Band C displays a pure ladder pattern without evidence of intact DNA, indicating a homogeneous apoptotic population. *A population of viable cells* - **Viable cells** maintain intact genomic DNA that remains as a single **high molecular weight band** near the top of the gel. - The **fragmented ladder pattern** in band C is incompatible with viable cell DNA, which should show minimal degradation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 63-64.

Q: An 80-year-old Parkinsonism patient died due to pneumonia. All are true about the heart histopathology slide except:

Positive Acid fast staining. ***Positive Acid fast staining*** - **Lipofuscin**, the pigment associated with brown atrophy and seen in aging hearts, does **not** stain positive with **Acid-fast stain**. - Acid-fast staining is typically used to identify **mycobacteria** (e.g., *Mycobacterium tuberculosis*) due to their mycolic acid content in the cell wall. *Peri-lysosomal location pigment* - **Lipofuscin** is an "wear-and-tear" pigment that accumulates within the **lysosomes** of cells, particularly in long-lived post-mitotic cells like cardiac myocytes [1]. - Its accumulation is a hallmark of cellular aging and is found in a **peri-lysosomal** distribution [1]. *Golden Brown pigment* - **Lipofuscin** characteristically appears as a **golden-brown** granular pigment under light microscopy [1]. - This color is due to its complex lipid and protein composition, resulting from the oxidation of unsaturated lipids and proteins. *Seen in Brown atrophy* - The accumulation of **lipofuscin** in cardiac myocytes, combined with a reduction in cell size (atrophy), leads to the gross appearance of the heart as smaller and brownish, a condition known as **brown atrophy**. - This is a common finding in the hearts of elderly individuals or those with chronic wasting diseases. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, p. 75.

Question 1

Caspase-1 mediated cell death with inflammation is known as

Accepted Answer

Pyroptosis

Answer

Necroptosis

Answer

Necrosis

Answer

Ferroptosis

Question 2

A middle-aged man from an endemic region presents with progressive swelling of the lower limb. A peripheral blood smear shows the following structure. What is the most likely cause of his limb swelling?

Accepted Answer

Lymphatic obstruction

Answer

Hypoalbuminemia

Answer

Hypoproteinemia

Answer

Increased hydrostatic pressure

Question 3

Which of the following types of cell death involves activation of caspase enzymes?

Accepted Answer

Apoptosis and Pyroptosis

Answer

Necrosis and Apoptosis

Answer

Apoptosis only

Answer

Apoptosis and necroptosis

Question 4

A 2-year-old child presents with growth retardation, pallor, bruising and has palpable spleen 5 cm below left costal margin. Bone marrow examination is shown below. Which is incorrect about the clinical diagnosis? (Recent NEET Pattern 2016-17)

Accepted Answer

Defect on chromosome 3

Answer

Glucosylceramide accumulation in reticulo-endothelial cells

Answer

Bleeding episodes

Answer

Erlenmeyer flask deformity of the distal femur

Question 5

Postmortem lung specimen of a patient who developed severe respiratory distress and petechiae after fracture of shaft of femur is given below. All are true about the condition except:

Accepted Answer

Diffuse white matter petechial hemorrhages

Answer

Noncardiogenic pulmonary edema

Answer

GURD criteria

Answer

Oil Red O stain for fat

Question 6

A 6-month-old child presents with loss of vision and regression of milestones. On examination hepatosplenomegaly and lymphadenopathy is seen. The bone marrow aspiration shows abnormal macrophage shown below. It stains positive for fat and negative for iron. Identify the cell.

Accepted Answer

Niemann-Pick cell

Answer

Gaucher cell

Answer

Hemosiderosis

Answer

Hallervorden-Spatz disease

Question 7

A 50-year-old patient with family history positive for premature coronary artery disease is found to have lumps on Achilles tendon. Biopsy from the lesion shows presence of:

Accepted Answer

Touton giant cell

Answer

Foam cell

Answer

Fatty streak

Answer

Langhan's giant cells

Question 8

A 22-year-old biker had a road traffic accident with bilateral tibia fracture. After 7 days, his condition suddenly worsens and leads to death. Pathological specimen is provided. What could be the likely cause of death?

Accepted Answer

Fat embolism

Answer

Septic shock

Answer

Pulmonary thromboembolism

Answer

Air embolism

Question 9

Agarose gel electrophoresis from DNA of a population of cells as seen under ultraviolet light is shown below. What is the correct explanation for the finding seen in the band labeled as "C"?

Accepted Answer

Apoptotic cells

Answer

Predominantly necrotic cells

Answer

Mixed population of normal and apoptotic cells

Answer

A population of viable cells

Question 10

An 80-year-old Parkinsonism patient died due to pneumonia. All are true about the heart histopathology slide except:

Accepted Answer

Positive Acid fast staining

Answer

Peri-lysosomal location pigment

Answer

Golden Brown pigment

Answer

Seen in Brown atrophy

General Pathology — MCQs

General Pathology — MCQs

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