General Pathology Practice Questions

Q: The mother of a newborn boy is alarmed that her baby regurgitates at every feeding. An endoscopic examination reveals that the child's esophagus is almost completely occluded. This finding represents an example of which of the following errors of morphogenesis?

Atresia. **Explanation:** The clinical presentation of a newborn with immediate regurgitation and an occluded esophagus is a classic description of **Esophageal Atresia** [1]. **1. Why Atresia is Correct:** In embryology, **Atresia** refers to the congenital absence or closure of a normal body orifice or tubular organ. During the 4th to 6th weeks of development, the esophagus undergoes a period of rapid epithelial proliferation that temporarily occluded the lumen. This is followed by **recanalization**. Failure of this recanalization process results in atresia. In the esophagus, this is often associated with a Tracheoesophageal Fistula (TEF). **2. Analysis of Incorrect Options:** * **Aplasia:** Refers to the complete failure of an organ or tissue to develop, despite the presence of its primordial precursor. In this case, the esophagus exists but is not patent. * **Dysplasia:** Refers to abnormal organization of cells within tissues, resulting in altered morphology (e.g., fibrous dysplasia of bone or precancerous epithelial changes). It is a qualitative defect, not a structural occlusion. * **Dysraphic Anomaly:** Refers to a failure of fusion of homologous structures along the midline. The most common examples are neural tube defects like Spina Bifida or Craniorachischisis. **3. NEET-PG High-Yield Pearls:** * **Most Common Type:** The most common variant of TEF is **Type C** (Esophageal atresia with a distal fistula), occurring in ~85% of cases [1]. * **Clinical Sign:** Look for "Maternal Polyhydramnios" in the history, as the fetus cannot swallow amniotic fluid [1]. * **Associated Syndrome:** Often part of the **VACTERL** association (Vertebral, Anal atresia, Cardiac, TEF, Renal, Limb defects). * **Diagnosis:** Inability to pass a nasogastric tube into the stomach; confirmed by an X-ray showing the tube coiled in the upper esophageal pouch [1].

Q: Two siblings have osteogenesis imperfecta, but their parents are normal. What is the most likely mechanism of inheritance?

Germline mosaicism. **Explanation:** The correct answer is **Germline mosaicism** (also known as gonadal mosaicism). **1. Why Germline Mosaicism is correct:** Osteogenesis Imperfecta (OI) is typically an **Autosomal Dominant (AD)** disorder. When two siblings are affected but both parents are phenotypically normal (and test negative for the mutation in their blood/somatic cells), the most likely explanation is that one parent carries the mutation specifically in a subset of their **germ cells** (sperm or eggs). Since the mutation is absent in the parent's somatic cells, they remain healthy, but they can pass the mutation to multiple offspring. This explains the recurrence in siblings without a family history. **2. Why the other options are incorrect:** * **Anticipation:** Refers to the increasing severity or earlier onset of a disease in successive generations (e.g., Huntington’s disease, Fragile X). It does not explain how normal parents have two affected children. * **Genomic Imprinting:** Involves differential expression of a gene depending on which parent it is inherited from (e.g., Prader-Willi/Angelman syndromes). It does not typically result in the recurrence of an AD condition from normal parents. * **New Mutation (De novo):** While a new mutation can cause OI in a child of normal parents, the probability of a *de novo* mutation occurring twice in the same family (affecting two siblings) is statistically negligible. **Clinical Pearls for NEET-PG:** * **Germline Mosaicism** is a classic "trap" for AD conditions like **Osteogenesis Imperfecta** and **Duchenne Muscular Dystrophy (DMD)**. * Always suspect germline mosaicism when **two or more siblings** are affected by an AD or X-linked disorder, but the parents are clinically and genetically normal. * **OI Type II** (the lethal perinatal form) is the most common subtype associated with germline mosaicism in board exams.

Q: Which of the following phospholipids serves as a marker of apoptosis?

Phosphatidylserine. **Explanation:** **Phosphatidylserine (PS)** is the correct answer because of its unique distribution in the cell membrane. In healthy cells, the enzyme **flippase** actively maintains PS on the **inner (cytoplasmic) leaflet** of the plasma membrane. During apoptosis, this asymmetry is lost due to the inactivation of flippase and the activation of **scramblase**. Consequently, PS "flips" to the **outer leaflet** (extracellular surface). This "PS exposure" acts as an "eat-me" signal, recognized by macrophages for phagocytosis without triggering inflammation. Clinical detection of this shift is commonly done using **Annexin V** staining in flow cytometry. **Analysis of Incorrect Options:** * **Phosphatidylinositol (A):** Primarily located on the inner leaflet, it serves as a precursor for second messengers like $IP_3$ and $DAG$ and anchors proteins via GPI linkages. It is not a marker for apoptosis. * **Phosphatidylcholine (C):** The most abundant phospholipid in the eukaryotic membrane, typically found on the outer leaflet. It serves a structural role and is not a signaling marker for cell death. * **Phosphatidylethanolamine (D):** Found mainly in the inner leaflet and involved in membrane fusion and cytokinesis, but its translocation is not the primary diagnostic marker for apoptosis. **High-Yield NEET-PG Pearls:** * **Annexin V:** A protein that binds specifically to Phosphatidylserine in the presence of $Ca^{2+}$; used to identify early apoptotic cells. * **Flippase vs. Scramblase:** Flippase (ATP-dependent) moves PS inward; Scramblase (Ca-activated) moves phospholipids non-specifically in both directions. * **Cardiolipin:** A phospholipid found exclusively in the inner mitochondrial membrane; its oxidation is also linked to the intrinsic pathway of apoptosis.

Q: Familial amyloid polyneuropathy is due to amyloidosis of nerves caused by deposition of which of the following?

Mutant transthyretin. **Explanation:** **Familial Amyloid Polyneuropathy (FAP)**, also known as Transthyretin Amyloidosis (ATTR), is an autosomal dominant multisystem disorder. The correct answer is **Mutant transthyretin (Option C)**. Transthyretin (TTR) is a transport protein synthesized primarily in the liver that carries thyroxine and retinol-binding protein. In FAP, a genetic mutation (most commonly **Val30Met**) causes the TTR protein to become unstable, misfold, and aggregate into insoluble amyloid fibrils. These fibrils deposit preferentially in the peripheral and autonomic nerves, leading to progressive sensorimotor neuropathy and autonomic dysfunction. **Analysis of Incorrect Options:** * **Amyloid associated protein (AA):** This is found in **Secondary Amyloidosis**, typically resulting from chronic inflammatory conditions (e.g., Rheumatoid Arthritis, Osteomyelitis). * **Mutant calcitonin:** This forms amyloid deposits in **Medullary Carcinoma of the Thyroid**. * **Normal transthyretin (Wild-type):** While normal TTR can deposit as amyloid, it causes **Senile Systemic Amyloidosis**, which primarily affects the heart in elderly patients, rather than the hereditary polyneuropathy seen in younger populations. **High-Yield Clinical Pearls for NEET-PG:** * **Most common mutation:** Valine substituted by Methionine at position 30 (Val30Met). * **Primary organ of synthesis:** Liver (This is why liver transplantation was historically a treatment strategy). * **Staining:** Like all amyloids, it shows **Apple-green birefringence** under polarized light with Congo Red stain. * **Newer Treatments:** TTR stabilizers (Tafamidis) and gene-silencing therapies (Patisiran).

Q: Patau syndrome is caused by which chromosomal abnormality?

Trisomy 13. **Explanation:** **Patau syndrome** is a severe genetic disorder caused by **Trisomy 13** (the presence of an extra copy of chromosome 13) [1]. It is the least common and most severe of the three viable autosomal trisomies. The underlying mechanism is usually **meiotic non-disjunction**, most frequently associated with advanced maternal age. **Analysis of Options:** * **Trisomy 13 (Correct):** Characterized by a classic triad of **Microphthalmia, Cleft lip/palate, and Polydactyly** [1]. It also involves severe CNS malformations like holoprosencephaly and scalp defects (aplasia cutis congenita). * **Trisomy 21 (Option A):** This is **Down Syndrome**, the most common autosomal trisomy [1]. Key features include Brushfield spots, Simian crease, and early-onset Alzheimer’s. * **Trisomy 18 (Option B):** This is **Edwards Syndrome** [1]. It is characterized by "rocker-bottom feet," clenched fists with overlapping fingers, and micrognathia. * **18p deletion (Option C):** This refers to Monosomy 18p, a rare chromosomal deletion syndrome distinct from the numerical trisomies. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Trisomies:** **P**atau (Trisomy **13** - **P**uberty age), **E**dwards (Trisomy **18** - **E**lection age), **D**own (Trisomy **21** - **D**rinking age). * **Patau Key Features:** Holoprosencephaly (failure of forebrain to divide), Polydactyly, and "punched-out" scalp lesions (**Aplasia cutis**). * **Screening:** On maternal serum screening, Patau syndrome typically shows **decreased** levels of free β-hCG and PAPP-A in the first trimester. * **Prognosis:** Extremely poor; most infants do not survive beyond the first year of life. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172.

Question 1

The mother of a newborn boy is alarmed that her baby regurgitates at every feeding. An endoscopic examination reveals that the child's esophagus is almost completely occluded. This finding represents an example of which of the following errors of morphogenesis?

Accepted Answer

Atresia

Answer

Aplasia

Answer

Dysplasia

Answer

Dysraphic anomaly

Question 2

Two siblings have osteogenesis imperfecta, but their parents are normal. What is the most likely mechanism of inheritance?

Accepted Answer

Germline mosaicism

Answer

Anticipation

Answer

Genomic imprinting

Answer

New mutation

Question 3

Metastatic calcification is commonly seen in all of the following, except:

Accepted Answer

Cardiac valves

Answer

Lungs

Answer

Kidneys

Answer

Gastric mucosa

Question 4

Which of the following phospholipids serves as a marker of apoptosis?

Accepted Answer

Phosphatidylserine

Answer

Phosphatidylinositol

Answer

Phosphatidylcholine

Answer

Phosphatidylethanolamine

Question 5

Familial amyloid polyneuropathy is due to amyloidosis of nerves caused by deposition of which of the following?

Accepted Answer

Mutant transthyretin

Answer

Amyloid associated protein

Answer

Mutant calcitonin

Answer

Normal transthyretin

Question 6

Patau syndrome is caused by which chromosomal abnormality?

Accepted Answer

Trisomy 13

Answer

Trisomy 21

Answer

Trisomy 18

Answer

18p deletion

Question 7

Congo red staining of abdominal fat has confirmed a diagnosis of Amyloidosis in a 28-year-old man. Which is the most common cause of death in primary AL Amyloidosis?

Accepted Answer

Cardiac failure

Answer

Respiratory failure

Answer

Renal failure

Answer

Septicemia

Question 8

A 56-year-old male patient complains of swelling in his legs. He is a known case of hypertension and is under treatment. On general physical examination, pitting edema is seen on the legs, and his TSH level is 3 mU/L. Which of the following is not a cause of this condition?

Accepted Answer

Myxedema

Answer

Increase in hydrostatic pressure

Answer

Decreased colloid osmotic pressure

Answer

Lymphatic obstruction

Question 9

Which of the following is NOT a form of reversible cellular injury?

Accepted Answer

Karyorrhexis

Answer

Vacuolar degeneration

Answer

Fat accumulation

Answer

Cell swelling

Question 10

Hemosiderin contains which of the following elements?

Accepted Answer

Iron

Answer

Calcium

Answer

Magnesium

Answer

None of the above

General Pathology — MCQs

General Pathology — MCQs

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