General Pathology Practice Questions

Q: Werner syndrome is characterized by which of the following?

Premature ageing. **Explanation:** **Werner Syndrome** is a rare autosomal recessive disorder characterized by **premature ageing** (progeria) [1]. It is caused by a mutation in the **WRN gene**, which encodes a member of the **RecQ helicase** family [1]. This enzyme is essential for DNA repair, replication, and maintaining telomere integrity. In its absence, cells accumulate genomic instability and enter replicative senescence prematurely, leading to the clinical manifestation of "adult progeria" [1]. **Analysis of Options:** * **A & B (MEN-I and MEN-II):** These are autosomal dominant syndromes involving endocrine tumors. While **Wermer Syndrome** (with an 'm') is another name for **MEN-I**, it is distinct from **Werner Syndrome** (with an 'n'). This is a common phonetic trap in exams. * **D (Defective sirtuins):** Sirtuins are NAD+-dependent deacetylases that promote longevity by inhibiting metabolic activity and increasing DNA repair. While decreased sirtuin activity is linked to the general aging process, it is not the primary molecular defect in Werner syndrome. **Clinical Pearls for NEET-PG:** * **Clinical Features:** Patients appear normal until puberty, followed by rapid aging: graying/loss of hair, bilateral cataracts, scleroderma-like skin changes, osteoporosis, and atherosclerosis. * **Malignancy Risk:** There is a significantly increased risk of rare cancers, particularly **soft tissue sarcomas** and osteosarcomas. * **Hutchinson-Gilford Progeria:** Unlike Werner (adult-onset), this is a childhood-onset progeria caused by mutations in the **LMNA gene** (Lamin A). * **Key Distinction:** Remember **Wermer** = MEN-1 (3 Ps: Pituitary, Parathyroid, Pancreas); **Werner** = WRN gene (Premature Ageing). **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. 77-78.

Q: What are the principal actions of prostacyclin in inflammation?

Vasodilation. **Explanation:** Prostacyclin (**PGI2**) is a potent lipid mediator derived from arachidonic acid via the cyclooxygenase (COX) pathway [1]. It is primarily produced by vascular endothelial cells. **1. Why Option A is Correct:** The principal actions of Prostacyclin (PGI2) are **vasodilation** and the **inhibition of platelet aggregation** [1]. In the context of inflammation, PGI2 promotes increased blood flow to the site of injury (hyperemia), which contributes to the clinical signs of redness and heat. It acts as a physiological antagonist to Thromboxane A2 (TXA2). **2. Why Other Options are Incorrect:** * **B. Vasoconstriction:** This is the primary action of **Thromboxane A2 (TXA2)** and certain Leukotrienes (LTC4, LTD4, LTE4) [1]. * **C. Increased Vascular Permeability:** This is primarily mediated by **Histamine**, Bradykinin, and Leukotrienes (LTC4, LTD4, LTE4) [1]. While PGI2 can potentiate edema by increasing blood flow, it does not directly cause endothelial cell contraction. * **D. Chemotaxis and Leukocyte Adhesion:** These are mediated by **Leukotriene B4 (LTB4)**, Chemokines (IL-8), and Complement components (C5a) [1]. **NEET-PG High-Yield Pearls:** * **The "Balance" Concept:** PGI2 (Vasodilator/Anti-aggregant) and TXA2 (Vasoconstrictor/Pro-aggregant) maintain vascular homeostasis. An imbalance is linked to thrombosis and atherosclerosis. * **Aspirin's Role:** Low-dose aspirin irreversibly inhibits COX-1 in platelets (reducing TXA2), but endothelial cells can regenerate COX to produce PGI2, leading to a net antithrombotic effect. * **Prostaglandins and Pain:** PGE2 is the primary prostaglandin responsible for pain (sensitizing nerve endings) and fever. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 95-96.

Q: What is the most important cytokine responsible for the synthesis of acute phase proteins?

IL-6. **Explanation:** **Correct Option: B (IL-6)** Interleukin-6 (IL-6) is the primary and most potent inducer of **acute-phase protein (APP)** synthesis by hepatocytes in the liver [1]. During inflammation, macrophages and other cells release cytokines that travel to the liver. IL-6 binds to its receptors on hepatocytes, activating the **JAK-STAT signaling pathway**, which leads to the transcription of genes for proteins like C-reactive protein (CRP), Fibrinogen, and Serum Amyloid A (SAA) [1]. While other cytokines contribute, IL-6 is considered the "chief" mediator of this systemic response. **Incorrect Options:** * **IL-1 & TNF-alpha:** These are "upstream" pro-inflammatory cytokines [1]. While they can stimulate the production of certain APPs and induce IL-6, their primary roles are in activating endothelium, inducing fever (via prostaglandin E2), and causing systemic manifestations like shock or cachexia [2]. * **IL-11:** This is a member of the IL-6 family and can stimulate APP synthesis, but its physiological contribution is significantly less than that of IL-6. It is clinically more relevant for its role in stimulating megakaryocytopoiesis (platelet production). **High-Yield Clinical Pearls for NEET-PG:** * **Positive APPs (Increase):** CRP (most sensitive), Fibrinogen (causes high ESR), Ferritin, Haptoglobin, and Complement proteins (C3, C4) [1]. * **Negative APPs (Decrease):** Albumin, Transferrin, and Transthyretin (Pre-albumin). * **ESR vs. CRP:** CRP rises and falls more rapidly than ESR, making it a better marker for acute changes. * **Hepcidin:** An acute-phase reactant induced by IL-6 that sequesters iron, leading to **Anemia of Chronic Disease**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 111. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 101.

Question 1

BRAF gene mutation is seen in which of the following conditions?

Accepted Answer

Melanoma

Answer

Breast carcinoma

Answer

Osteosarcoma

Answer

Prostate carcinoma

Question 2

What is the most reliable investigation for amyloidosis?

Accepted Answer

Kidney biopsy

Answer

Abdominal fat pad aspirate

Answer

Ultrasound (USG)

Answer

Urine examination

Question 3

Autoimmunity can be caused due to all of the following mechanisms except?

Accepted Answer

Negative selection of T-cells in the thymus

Answer

The pressure of forbidden clones

Answer

Expression of cryptic antigens

Answer

Inappropriate expression of MHC proteins

Question 4

Corpora amylacea are microscopic structures found in which of the following glands?

Accepted Answer

Prostate gland

Answer

Parotid gland

Answer

Pineal gland

Answer

Pituitary gland

Question 5

Werner syndrome is characterized by which of the following?

Accepted Answer

Premature ageing

Answer

Multiple Endocrine Neoplasia type I (MEN-I)

Answer

Multiple Endocrine Neoplasia type II (MEN-II)

Answer

Defective sirtuins

Question 6

Which of the following is NOT a clinical manifestation of Disseminated Intravascular Coagulation?

Accepted Answer

Brain edema

Answer

Microthrombi

Answer

Sheehan postpartum pituitary necrosis

Answer

Waterhouse-Friderichsen syndrome

Question 7

Gain of function mutation in the RAS gene is equivalent to a loss of function mutation in which of the following?

Accepted Answer

GAP protein

Answer

Rb

Answer

Bcr-tyrosine kinase

Answer

Bcl-2

Question 8

All of the following are types of selectin molecules except?

Accepted Answer

M-selectin

Answer

E-selectin

Answer

P-selectin

Answer

L-selectin

Question 9

What are the principal actions of prostacyclin in inflammation?

Accepted Answer

Vasodilation

Answer

Vasoconstriction

Answer

Increased vascular permeability

Answer

Chemotaxis, leukocyte adhesion

Question 10

What is the most important cytokine responsible for the synthesis of acute phase proteins?

Accepted Answer

IL-6

Answer

IL-1

Answer

IL-11

Answer

TNF alpha

General Pathology — MCQs

General Pathology — MCQs

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