FMGE 2025 Practice Questions

Q: A patient presents with gum bleeding, petechiae, poor wound healing, and other related symptoms. Which of the following vitamin deficiencies is most likely responsible for this presentation?

Vitamin C. ***Vitamin C*** - Vitamin C (ascorbic acid) is essential for the hydroxylation of **proline** and **lysine** residues during collagen synthesis, crucial for maintaining the integrity of blood vessels and skin. - Deficiency results in **scurvy**, characterized by defective collagen, leading to fragile capillaries (manifesting as **gum bleeding** and **petechiae**) and impaired **wound healing**. *Vitamin A* - Deficiency is primarily associated with visual disturbances, most notably **night blindness** (**nyctalopia**), and **xerophthalmia** (dry eyes). - Its main roles involve vision, epithelial differentiation, and immune function, not the stability of subendothelial collagen required to prevent bleeding tendencies described here. *Vitamin B6* - Pyridoxine deficiency symptoms include **seborrheic dermatitis**, **stomatitis**, **cheilosis**, and neurological issues like **peripheral neuropathy** and seizures in infants. - While involved in numerous metabolic pathways, its deficiency is not responsible for the characteristic symptoms of capillary fragility (petechiae and bleeding). *Vitamin B3* - Niacin deficiency causes **pellagra**, classically identified by the "3 D's": **Dermatitis** (photosensitive rash), **Diarrhea**, and **Dementia**. - Although pellagra involves epithelial changes (dermatitis), it does not typically present with the severe vascular fragility, gum manifestations, and poor generalized wound healing seen in scurvy.

Q: A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

Homogentisate oxidase. ***Homogentisate oxidase***- Deficiency of this enzyme causes **Alkaptonuria**, resulting in the accumulation of **homogentisic acid**, which oxidizes into dark polymeric pigment called **ochronotic pigment**.- This pigment deposits in cartilage and connective tissues (**Ochronosis**), leading to severe destructive arthritis, especially in large joints, and causing the characteristic **blackening of joint tissues** observed on arthroscopy.*Branched-chain alpha-ketoacid dehydrogenase*- Deficiency of this enzyme causes **Maple Syrup Urine Disease (MSUD)**, leading to the accumulation of **branched-chain amino acids** (leucine, isoleucine, valine).- MSUD is characterized by severe neurologic dysfunction and a distinctive maple syrup odor in the urine, not chronic arthritis or joint pigmentation.*Tyrosinase*- This enzyme is crucial for the synthesis of **melanin** from tyrosine.- Deficiency results in conditions like **Albinism**, characterized by hypopigmentation of the skin, hair, and eyes, which is distinct from ochronotic arthritis.*Fumarase*- Deficiency of this enzyme (Fumarate hydratase) impairs the **Krebs cycle** (TCA cycle).- Clinical features include severe intellectual disability, microcephaly, and metabolic acidosis, without the development of ochronosis or black joints.

Q: A patient with a history of strenuous exercise skipped a meal and later consumed alcohol at a party. Alcohol inhibits which of the following biochemical processes, potentially leading to hypoglycemia?

Gluconeogenesis. ***Gluconeogenesis*** - Alcohol metabolism by **alcohol dehydrogenase** and **aldehyde dehydrogenase** generates a massive influx of **NADH**, drastically increasing the hepatic NADH/NAD+ ratio. - This high NADH/NAD+ ratio shifts metabolic intermediates, inhibiting key enzymes (e.g., **lactate dehydrogenase** and **malate dehydrogenase**) required to convert precursors like lactate and amino acids into glucose, leading to failure of new glucose synthesis and subsequent hypoglycemia. *Glycogenolysis* - This process, the breakdown of stored **glycogen** into glucose, is not directly inhibited by the increased NADH ratio produced during alcohol metabolism. - In fact, the initial phase of alcohol-induced hypoglycemia relies on the depletion of pre-existing glycogen stores, which is accelerated by factors like strenuous exercise or fasting. *Hexose Monophosphate (HMP) Shunt* - The primary function of the HMP shunt is to produce **NADPH** (for reductive biosynthesis and antioxidant defense) and five-carbon sugars (**ribose-5-phosphate**) for nucleotide synthesis. - Inhibition of the HMP shunt alters cell redox status and nucleotide production but does not directly impair blood glucose maintenance or cause acute hypoglycemia. *Ketone Body Formation* - Alcohol metabolism actually tends to **inhibit** ketone body formation because the high NADH ratio inhibits **beta-oxidation** of fatty acids in the liver, which is required to produce the Acetyl-CoA necessary for ketogenesis. - While ketone formation is inhibited, this is a consequence of high NADH, and the hypoglycemia itself results from the inability to synthesize glucose via gluconeogenesis, not the absence of ketones.

Q: Which of the following accumulates in the mucopolysaccharidosis associated with Natowicz disease?

Hyaluronic acid. ***Hyaluronic acid***- Natowicz disease is synonymous with **Mucopolysaccharidosis type IX (MPS IX)**, a highly rare lysosomal storage disorder.- This condition is caused by a deficiency in the enzyme **hyaluronidase (HYAL1)**, which results in the failure to degrade **hyaluronic acid**, leading to its massive accumulation.*Dermatan sulfate*- Accumulation of **dermatan sulfate** is the defining characteristic of MPS I (Hurler, Scheie), MPS II (Hunter), and MPS VI (Maroteaux-Lamy).- These disorders generally involve widespread visceral, skeletal, and neurological pathology, unlike the localized features of MPS IX.*Heparan sulfate*- **Heparan sulfate** accumulates primarily in the various subtypes of **Sanfilippo syndrome (MPS III)**, as well as MPS I and II.- MPS III is predominantly characterized by progressive **neurocognitive decline** with relatively mild somatic features compared to other MPS types.*Keratan sulfate*- Accumulation of **keratan sulfate** is the metabolic hallmark of **Morquio syndrome (MPS IV)**, a disorder primarily presenting with severe skeletal dysplasia.- MPS IV involves deficiencies in either *N*-acetylgalactosamine-6-sulfatase or $\beta$-galactosidase, not hyaluronidase.

Q: Which drug is preferred for management of diabetes in a patient with cardiac and renal failure?

SGLT2 inhibitors. ***SGLT2 inhibitors*** - These agents are strongly recommended due to their proven benefits in reducing **heart failure (HF)** hospitalizations and **cardiovascular (CV) mortality**. - They also offer robust **reno-protection**, slowing the decline of **eGFR** and reducing albuminuria, making them ideal when both cardiac and renal failure coexist. *Pioglitazone* - This drug class (**thiazolidinediones**) is known to cause **fluid retention** and peripheral edema, thus potentially exacerbating or precipitating **congestive heart failure (CHF)**; it is therefore generally avoided [1]. - It is not associated with improved long-term renal or cardiovascular outcomes in the way that SGLT2 inhibitors are. *Metformin* - While a foundational drug, Metformin is contraindicated in severe **renal failure** (e.g., eGFR <30 mL/min/1.73m²) due to the increased risk of potentially fatal **lactic acidosis**. - Although safe in mild to moderate CKD, it lacks the specific, compelling evidence for reducing progression of **heart failure** or **CKD** compared to SGLT2 inhibitors. *Sulfonylureas* - These drugs primarily increase the risk of **hypoglycemia**, which is heightened in patients with **renal insufficiency** due to altered drug metabolism and clearance. - They provide no demonstrated **cardiovascular** or **renal protective benefits** and may be associated with weight gain.

Q: Which adverse effect of Bleomycin is exacerbated by radiation exposure?

Pulmonary toxicity. ***Pulmonary toxicity*** - Bleomycin is well-known for causing dose-dependent **pulmonary fibrosis**. It damages **type I pneumocytes**, leading to inflammation, proliferation of **type II pneumocytes**, and eventual fibrosis, impairing gas exchange. - The risk of pulmonary toxicity is significantly increased by concurrent or prior **chest radiation therapy** and administration of high concentrations of supplemental **oxygen**, as both are also injurious to lung tissue. *Gastric toxicity* - Bleomycin is not typically associated with significant gastric toxicity. Common side effects are milder and include **mucositis** and **stomatitis** rather than severe gastric damage. - There is no evidence of a synergistic toxic effect on the gastric mucosa when Bleomycin is combined with radiation therapy. *Neural toxicity* - Neurotoxicity is not a characteristic side effect of Bleomycin. Chemotherapeutic agents like **vincristine** and **cisplatin** are more commonly associated with peripheral neuropathy. - While radiation can cause nerve damage, this is not a known interaction that is specifically exacerbated by Bleomycin administration. *Hepatotoxicity* - Severe liver damage (**hepatotoxicity**) is a rare side effect of Bleomycin. Mild and transient elevations of liver enzymes may occur but are not clinically significant. - Unlike the lungs, the liver is not a primary site for synergistic toxicity between Bleomycin and radiation therapy.

Q: A 25-year-old woman presents to the emergency department 6 hours after ingesting a large quantity of paracetamol tablets. What is the most likely progression of paracetamol poisoning in this case?

Increase in liver enzymes starting around 24 hours. ***Increase in liver enzymes starting around 24 hours*** - Phase 2 of paracetamol toxicity, occurring **24–72 hours post-ingestion**, is characterized by the onset of **hepatotoxicity**, marked by rising **AST** and **ALT** levels. - The patient is currently 6 hours post-ingestion (late Phase 1), so the most likely progression is entering Phase 2, where biochemical evidence of liver damage begins around 24 hours and continues to rise. *Liver failure within 24 hours* - **Acute liver failure** (manifested by coagulopathy, jaundice, and encephalopathy) typically develops around 3 to 4 days (72–96 hours) post-ingestion (Phase 3). - Within the first 24 hours, symptoms are usually mild or absent (Phase 1: nausea, vomiting, or asymptomatic). *Paracetamol achieves peak concentration within 4 hours* - While **peak plasma concentration** for standard paracetamol typically occurs around 4 hours post-ingestion, this pharmacokinetic event has already occurred since the patient presents at 6 hours. - The question asks for the subsequent toxicological *progression* (clinical course), not a past pharmacokinetic event. *Recovery within 72 hours* - Recovery (Phase 4) typically occurs after the peak injury period (around 4 days or later), especially with effective antidote treatment (**N-acetylcysteine**). - Given the ingestion of a **large quantity**, the patient is expected to progress through Phase 2 (**hepatotoxicity** at 24-72 hours) and possibly Phase 3 (peak toxicity at 72-96 hours), not recover within 72 hours.

Q: A patient with rheumatoid arthritis is taking indomethacin and an ACE inhibitor for hypertension. What potential side effect is likely to be seen?

Hyperkalemia. ***Hyperkalemia*** - The co-administration of an **ACE inhibitor** and an **NSAID (indomethacin)** significantly increases the risk of **hyperkalemia** due to synergistic effects on renal potassium balance. - **ACE inhibitors** directly block aldosterone synthesis (leading to reduced potassium excretion), while **NSAIDs** reduce prostaglandin synthesis, impairing renin release, which also suppresses aldosterone effect. *Hypercalcemia* - This scenario is not associated with hypercalcemia; drugs notorious for causing hypercalcemia include **thiazide diuretics**, or conditions like **primary hyperparathyroidism**. - Neither ACE inhibitors nor NSAIDs directly impair calcium homeostasis leading to clinically significant increases. *Hypernatremia* - **ACE inhibitors** decrease aldosterone levels, which promotes sodium excretion, typically resulting in **hyponatremia** or normonatremia, not hypernatremia. - Although NSAIDs can cause fluid retention, this is largely due to increased water reabsorption leading to expansion of extracellular fluid, not an increase in serum sodium concentration. *Hyperphosphatemia* - **Hyperphosphatemia** is primarily seen in end-stage **chronic kidney disease (CKD)** because the kidneys cannot excrete phosphate effectively. - The combination of indomethacin and an ACE inhibitor does not directly impair phosphate excretion via the mechanisms needed to cause clinically significant hyperphosphatemia.

Q: Scientists administered norepinephrine to guinea pigs, resulting in an increase in systolic and diastolic blood pressure and a decrease in heart rate. What mechanism explains this response?

Baroreceptor stimulation. ***Baroreceptor stimulation***- The administration of **norepinephrine** causes a massive increase in **systemic vascular resistance (SVR)** via activation of **alpha-1 receptors**, leading to severe hypertension (increased SBP and DBP).- This sudden rise in blood pressure activates arterial **baroreceptors** (in the carotid sinus and aortic arch), triggering a robust compensatory increase in **vagal tone** (parasympathetic outflow), which results in reflex **bradycardia**. *Beta-1 receptor blockade*- Beta-1 receptor blockade would decrease cardiac output and prevent the direct chronotropic effect of norepinephrine, but it would also lead to a **decrease** in SBP rather than the observed rise.- This mechanism cannot explain the severe **hypertension** observed, as norepinephrine's primary pressor effect (vasoconstriction) is mediated by **alpha-1 receptors**. *Alpha-1 receptor blockade*- Alpha-1 receptor blockade would prevent **vasoconstriction**, leading to a significant **drop** in both systolic and diastolic blood pressure, which directly contradicts the finding of increased SBP and DBP.- The hypertensive effect observed requires the potent activation of **alpha-1 receptors** by norepinephrine. *Baroreceptor inhibition*- If the baroreceptors were inhibited, the reflex mechanism would be absent, and the direct effect of norepinephrine on cardiac **beta-1 receptors** would dominate.- This direct stimulation would cause **tachycardia** (increased heart rate), which is the opposite of the observed physiological response.

Question 1

A patient presents with gum bleeding, petechiae, poor wound healing, and other related symptoms. Which of the following vitamin deficiencies is most likely responsible for this presentation?

Accepted Answer

Vitamin C

Answer

Vitamin B3

Answer

Vitamin B6

Answer

Vitamin A

Question 2

A patient presents with arthritis, and arthroscopy reveals blackening of the joints. Which enzyme deficiency is most likely responsible for this condition?

Accepted Answer

Homogentisate oxidase

Answer

Fumarase

Answer

Tyrosinase

Answer

Branched-chain alpha-ketoacid dehydrogenase

Question 3

A patient with a history of strenuous exercise skipped a meal and later consumed alcohol at a party. Alcohol inhibits which of the following biochemical processes, potentially leading to hypoglycemia?

Accepted Answer

Gluconeogenesis

Answer

Glycogenolysis

Answer

Ketone Body Formation

Answer

Hexose Monophosphate (HMP) Shunt

Question 4

Which of the following accumulates in the mucopolysaccharidosis associated with Natowicz disease?

Accepted Answer

Hyaluronic acid

Answer

Dermatan sulfate

Answer

Heparan sulfate

Answer

Keratan sulfate

Question 5

Which drug is preferred for management of diabetes in a patient with cardiac and renal failure?

Accepted Answer

SGLT2 inhibitors

Answer

Pioglitazone

Answer

Metformin

Answer

Sulfonylureas

Question 6

Which adverse effect of Bleomycin is exacerbated by radiation exposure?

Accepted Answer

Pulmonary toxicity

Answer

Neural toxicity

Answer

Hepatotoxicity

Answer

Gastric toxicity

Question 7

What is the key difference between Cisplatin and Carboplatin?

Accepted Answer

Cisplatin has more nephrotoxic side effects compared to Carboplatin

Answer

Cisplatin is less neurotoxic than Carboplatin

Answer

Carboplatin is more neurotoxic than Cisplatin

Answer

Cisplatin causes fewer gastric issues compared to Carboplatin

Question 8

A 25-year-old woman presents to the emergency department 6 hours after ingesting a large quantity of paracetamol tablets. What is the most likely progression of paracetamol poisoning in this case?

Accepted Answer

Increase in liver enzymes starting around 24 hours

Answer

Recovery within 72 hours

Answer

Paracetamol achieves peak concentration within 4 hours

Answer

Liver failure within 24 hours

Question 9

A patient with rheumatoid arthritis is taking indomethacin and an ACE inhibitor for hypertension. What potential side effect is likely to be seen?

Accepted Answer

Hyperkalemia

Answer

Hypercalcemia

Answer

Hypernatremia

Answer

Hyperphosphatemia

Question 10

Scientists administered norepinephrine to guinea pigs, resulting in an increase in systolic and diastolic blood pressure and a decrease in heart rate. What mechanism explains this response?

Accepted Answer

Baroreceptor stimulation

Answer

Alpha-1 receptor blockade

Answer

Beta-1 receptor blockade

Answer

Baroreceptor inhibition

FMGE 2025

Biochemistry

Internal Medicine

Pharmacology

Physiology