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USMLE Step 1 study materials
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USMLE Step 1 practice questions

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Question 1General Principles of Foundational Science

A reversible inhibitor binds the free enzyme at the substrate-binding site. Which change in Michaelis-Menten parameters describes its effect?

  1. Km rises, Vmax unchanged Correct answer.
  2. Both Km and Vmax fall
  3. Vmax rises with Km unchanged
  4. Vmax falls, Km unchanged

Explanation

A competitive inhibitor competes with substrate at the active site, so sufficiently high substrate concentration can outcompete it; apparent Km increases while Vmax is unchanged. Inhibitors that lower Vmax without changing Km act at a site other than the substrate-binding site.

Question 2General Principles of Foundational Science

Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate. Which cofactor is covalently attached to this enzyme and required for its activity?

  1. Cobalamin
  2. Biotin Correct answer.
  3. Pyridoxal phosphate
  4. Thiamine pyrophosphate

Explanation

Carboxylase reactions that add CO2 to a substrate use biotin, which is linked by an amide bond to a lysine residue and carries activated bicarbonate. Pyruvate carboxylase is the biotin-dependent anaplerotic enzyme that replenishes oxaloacetate.

Question 3General Principles of Foundational Science

During DNA replication, which enzyme separates the two parental strands at the replication fork?

  1. DNA ligase
  2. Topoisomerase
  3. Helicase Correct answer.
  4. Primase

Explanation

DNA helicase disrupts the hydrogen bonds between complementary base pairs, unwinding the duplex to expose the single-stranded templates. The other fork enzymes act on the primers, the supercoiling, or the joining of fragments.

Question 4General Principles of Foundational Science

In eukaryotic translation, which codon signals the initiation of protein synthesis?

  1. UGA
  2. GUG
  3. UAA
  4. AUG Correct answer.

Explanation

AUG is the eukaryotic start codon and also encodes methionine, so the initiator tRNA carrying methionine is placed in the P site. UAA and UGA are termination codons.

Question 5General Principles of Foundational Science

Both parents are phenotypically normal carriers of the same autosomal recessive disorder. What is the probability that their next child will be affected?

  1. 25% Correct answer.
  2. 75%
  3. 100%
  4. 50%

Explanation

Two heterozygous (Aa) parents produce offspring in a 1:2:1 genotypic ratio, so one quarter are homozygous recessive and affected. Each pregnancy is an independent event with the same risk.

Question 6General Principles of Foundational Science

The Na+/K+-ATPase of the plasma membrane transports ions in which stoichiometry per molecule of ATP hydrolyzed?

  1. Two Na+ out, three K+ in
  2. One Na+ out, one K+ in
  3. Three Na+ out, two K+ in Correct answer.
  4. Three Na+ in, two K+ out

Explanation

The pump moves three sodium ions out of the cell and two potassium ions in per ATP, producing a net export of one positive charge. This electrogenic action helps maintain the resting membrane potential and the low intracellular sodium concentration used for secondary active transport.

Question 7General Principles of Foundational Science

E. coli is grown in medium containing abundant lactose and no glucose. Which combination best describes the state of the lac operon?

  1. Repressor off operator; CAP active Correct answer.
  2. Repressor on operator; CAP active
  3. Repressor on operator; CAP inactive
  4. Repressor off operator; CAP inactive

Explanation

Lactose (as allolactose) binds the repressor and releases it from the operator, while the absence of glucose raises cAMP so CAP binds its site and activates transcription. Repressor removal plus CAP activation gives maximal expression of the operon.

Question 8General Principles of Foundational Science

A mutation deletes the AAUAAA signal from the 3' untranslated region of a gene. What is the most likely consequence for the transcript?

  1. Loss of the poly(A) tail Correct answer.
  2. Failure of 5' cap addition
  3. Failure of intron splicing
  4. Failure of tRNA charging

Explanation

The AAUAAA sequence directs cleavage of the nascent transcript and addition of the poly(A) tail, which protects the mRNA from exonuclease degradation and assists nuclear export and translation. Loss of the signal destabilizes the transcript.

Question 9General Principles of Foundational Science

Following DNA damage, activated p53 halts the cell cycle in G1 by which mechanism?

  1. Phosphorylation of Rb by p53
  2. Proteasomal degradation of p27
  3. Activation of CDK4-cyclin D complexes
  4. Induction of p21, which inhibits CDKs Correct answer.

Explanation

p53 is a transcription factor that induces p21, a CDK inhibitor that blocks cyclin E-CDK2 activity and keeps Rb hypophosphorylated, so E2F remains sequestered and the G1/S transition is prevented. This allows time for DNA repair.

Question 10General Principles of Foundational Science

Cytochrome c escapes from the mitochondrial intermembrane space into the cytosol during apoptosis. Which caspase is directly activated in this pathway?

  1. Caspase-9 Correct answer.
  2. Caspase-1
  3. Caspase-3
  4. Caspase-8

Explanation

Cytochrome c complexes with Apaf-1 to form the apoptosome, which recruits and activates the initiator caspase-9. Caspase-9 then cleaves and activates executioner caspase-3.

Question 11General Principles of Foundational Science

An infant has fasting hypoglycemia, hepatomegaly, lactic acidosis, and elevated liver glycogen. Deficiency of which enzyme best explains this presentation?

  1. Glucose-6-phosphatase Correct answer.
  2. Muscle glycogen phosphorylase
  3. Acid alpha-glucosidase
  4. Debranching enzyme

Explanation

Glucose-6-phosphatase deficiency (von Gierke disease) prevents the liver from converting glucose-6-phosphate into free glucose, so fasting hypoglycemia occurs while glucose-6-phosphate is shunted to glycogen and lactate. Glycogen accumulates and causes hepatomegaly.

Question 12General Principles of Foundational Science

A neonate develops lethargy and hyperammonemia after feeding. Urinary orotic acid is markedly elevated and blood urea nitrogen is low. Deficiency of which enzyme is most likely?

  1. Argininosuccinate lyase
  2. Arginase
  3. Carbamoyl phosphate synthetase I
  4. Ornithine transcarbamylase Correct answer.

Explanation

Ornithine transcarbamylase transfers carbamoyl phosphate to ornithine; when deficient, carbamoyl phosphate accumulates and is diverted into pyrimidine synthesis, producing excess orotic acid. Hyperammonemia results from the blocked urea cycle.

Question 13General Principles of Foundational Science

A boy shows hyperuricemia, choreoathetosis, spasticity, and self-mutilating behavior. Deficiency of which enzyme underlies this disorder?

  1. Adenosine deaminase
  2. Xanthine oxidase
  3. HGPRT Correct answer.
  4. PRPP synthetase

Explanation

Hypoxanthine-guanine phosphoribosyltransferase loss impairs purine salvage, so hypoxanthine and guanine are degraded to uric acid while rising PRPP drives de novo purine synthesis. The neurological features are characteristic of Lesch-Nyhan syndrome.

Question 14General Principles of Foundational Science

A drug has a very large apparent volume of distribution. This finding most likely indicates that the drug is:

  1. Highly bound to plasma albumin
  2. Confined largely to plasma
  3. Distributed extensively into tissues Correct answer.
  4. Excreted only by glomerular filtration

Explanation

Volume of distribution equals the amount of drug in the body divided by its plasma concentration, so a large value means most of the drug has left the plasma and partitioned into tissues. The calculated value is apparent rather than a true anatomic space.

Question 15General Principles of Foundational Science

A competitive antagonist is added to a tissue preparation at a fixed concentration. How does the agonist dose-response curve change?

  1. Lowers Emax without a shift
  2. Rightward shift, Emax unchanged Correct answer.
  3. Shifts right and lowers Emax
  4. Leftward shift, Emax unchanged

Explanation

A competitive antagonist binds reversibly at the agonist site, so increasing the agonist concentration can overcome the blockade and restore the full maximal response; only potency falls, shifting the curve right. A reduction in Emax indicates noncompetitive or irreversible antagonism.

Question 16General Principles of Foundational Science

Which receptor type mediates its effects through intrinsic enzymatic activity rather than through a G protein or a second messenger cascade?

  1. Nuclear hormone receptor
  2. Receptor tyrosine kinase Correct answer.
  3. G protein-coupled receptor
  4. Ligand-gated ion channel

Explanation

Receptor tyrosine kinases such as the insulin receptor autophosphorylate on ligand binding and then phosphorylate downstream adaptor proteins like IRS-1. Their kinase domain is part of the receptor itself.

Question 17General Principles of Foundational Science

A child has ataxia, seizures, and inappropriate laughter. Cytogenetic studies show a deletion of the maternal copy of chromosome 15q11-q13. Which diagnosis fits?

  1. Angelman syndrome (ataxia, seizures, laughter) Correct answer.
  2. Silver-Russell syndrome (growth restriction)
  3. Prader-Willi syndrome (hypotonia, hyperphagia)
  4. Beckwith-Wiedemann syndrome (macrosomia)

Explanation

The 15q11-q13 region is imprinted, and neurons express only the maternal copy of UBE3A, so maternal deletion abolishes this gene's function and causes Angelman syndrome. Deletion of the paternal copy of the same region causes Prader-Willi syndrome.

Question 18General Principles of Foundational Science

A congenital autosomal recessive disorder affects 1 in 10,000 newborns in a population at Hardy-Weinberg equilibrium. What is the approximate carrier frequency?

  1. 1 in 100
  2. 1 in 10
  3. 1 in 25
  4. 1 in 50 Correct answer.

Explanation

The affected frequency equals q squared, so q equals 1/100 and p is approximately 0.99. The carrier frequency 2pq is therefore about 0.02, or 1 in 50.

Question 19General Principles of Foundational Science

A patient with a connective tissue disorder has impaired activity of a copper-dependent enzyme, and collagen fibrils show reduced tensile strength. Which step of collagen synthesis is most directly affected?

  1. Cross-linking of lysine residues Correct answer.
  2. Glycosylation of hydroxylysine
  3. Hydroxylation of proline residues
  4. Cleavage of terminal propeptides

Explanation

Lysyl oxidase, which requires copper, oxidatively deaminates lysine and hydroxylysine to reactive aldehydes that form covalent cross-links between adjacent collagen molecules, giving fibrils their strength. Loss of this step produces weak, stretchy connective tissue.

Question 20General Principles of Foundational Science

A 5-year-old develops numerous freckle-like lesions and skin cancers on sun-exposed skin. Cultured fibroblasts cannot remove UV-induced pyrimidine dimers. Which repair process is defective?

  1. Base excision repair of oxidized bases
  2. Mismatch repair of replication errors
  3. Homologous recombination of double-strand breaks
  4. Nucleotide excision repair Correct answer.

Explanation

Nucleotide excision repair excises bulky, helix-distorting lesions such as UV pyrimidine dimers; when it fails, mutations accumulate and cause xeroderma pigmentosum. Defects in the other pathways produce different diseases and different lesion spectra.

Question 21Behavioral Health & Nervous Systems/Special Senses

A dog learns to salivate when a bell is rung because the bell has been repeatedly paired with food. In this paradigm, the food is best described as which of the following?

  1. Unconditioned response
  2. Conditioned stimulus
  3. Conditioned response
  4. Unconditioned stimulus Correct answer.

Explanation

Classical conditioning pairs a neutral stimulus with a biologically potent stimulus. The food is the naturally effective stimulus that elicits salivation without prior training, so it is the unconditioned stimulus, and the salivation it produces is the unconditioned response.

Question 22Behavioral Health & Nervous Systems/Special Senses

A slot machine pays out after an unpredictable number of pulls, and this produces persistent, high-rate play that resists extinction. This schedule of reinforcement is which of the following?

  1. Fixed-ratio
  2. Fixed-interval
  3. Variable-interval
  4. Variable-ratio Correct answer.

Explanation

Reinforcement delivered after an unpredictable number of responses defines a variable-ratio schedule, which generates the highest and most extinction-resistant response rates. Predictable response counts or time-based delivery yield slower or more pause-prone behavior.

Question 23Behavioral Health & Nervous Systems/Special Senses

A medical student who feels hostile toward a supervisor instead pours that energy into warmly mentoring a junior student. Which defense mechanism is most likely being used?

  1. Regression
  2. Projection
  3. Sublimation Correct answer.
  4. Denial

Explanation

Sublimation is the mature defense in which an unacceptable impulse is channeled into a socially acceptable and productive activity. The hostile drive is redirected into mentoring rather than expressed or disavowed.

Question 24Behavioral Health & Nervous Systems/Special Senses

Which of the following EEG patterns is most characteristic of stage N3 sleep?

  1. Sleep spindles and K complexes
  2. Delta waves Correct answer.
  3. Sawtooth waves
  4. Alpha rhythm

Explanation

Stage N3, or slow-wave sleep, is defined by high-amplitude, low-frequency delta activity. The other listed patterns mark different states of arousal or sleep stages.

Question 25Behavioral Health & Nervous Systems/Special Senses

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the pathologic hallmark of which of the following?

  1. Multiple sclerosis
  2. Parkinson disease Correct answer.
  3. Alzheimer disease
  4. Huntington disease

Explanation

Loss of nigrostriatal dopamine neurons disinhibits the indirect pathway and increases indirect pathway output, producing rigidity, bradykinesia, and resting tremor. This selective nigral loss defines Parkinson disease.

Question 26Behavioral Health & Nervous Systems/Special Senses

A 62-year-old man speaks fluently but his speech conveys little meaning, he cannot follow simple commands, and he is unconcerned about his language problem. Which of the following is the most likely diagnosis?

  1. Broca aphasia
  2. Conduction aphasia
  3. Global aphasia
  4. Wernicke aphasia Correct answer.

Explanation

Wernicke aphasia follows damage to the dominant superior temporal gyrus and produces fluent but meaningless speech, impaired comprehension, and poor awareness of the deficit. Impaired repetition with preserved comprehension would instead point to a disconnection syndrome.

Question 27Behavioral Health & Nervous Systems/Special Senses

A patient walks with a wide-based gait and tends to fall toward the side of a cerebellar hemisphere lesion. Which of the following additional findings is most consistent with this lesion?

  1. Spasticity
  2. Loss of vibratory sense
  3. Dysdiadochokinesia Correct answer.
  4. Resting tremor

Explanation

Cerebellar hemisphere lesions cause ipsilateral limb ataxia, including impaired rapid alternating movements (dysdiadochokinesia), intention tremor, and overshoot on finger-to-nose testing. Truncal and gait ataxia predominate with midline vermal lesions.

Question 28Behavioral Health & Nervous Systems/Special Senses

The afferent limb of the pupillary light reflex is carried by which of the following nerves?

  1. Facial nerve (CN VII)
  2. Trigeminal nerve (CN V)
  3. Optic nerve (CN II) Correct answer.
  4. Oculomotor nerve (CN III)

Explanation

Retinal ganglion cell axons travel in the optic nerve to the pretectal area, which projects bilaterally to the Edinger-Westphal nuclei; the efferent limb then travels with the oculomotor nerve. Thus the optic nerve carries the sensory input of the reflex.

Question 29Behavioral Health & Nervous Systems/Special Senses

A patient has a left homonymous hemianopia with sparing of the macula. A lesion of which of the following structures is most likely responsible?

  1. Right occipital cortex Correct answer.
  2. Left optic nerve
  3. Optic chiasm
  4. Right optic tract

Explanation

Posterior cerebral artery infarction of the occipital pole spares the macular representation because the occipital pole also receives collateral supply from the middle cerebral artery. This produces a contralateral homonymous hemianopia with macular sparing.

Question 30Behavioral Health & Nervous Systems/Special Senses

A patient reports hearing loss in the left ear. On examination, the Weber test lateralizes to the left ear and the left ear hears bone conduction better than air conduction. Which of the following best describes the hearing loss in the left ear?

  1. Retrocochlear hearing loss
  2. Conductive hearing loss Correct answer.
  3. Sensorineural hearing loss
  4. Normal hearing with malingering

Explanation

In conductive loss, ambient sound is not masked by air conduction, so bone conduction exceeds air conduction on Rinne testing and the Weber test lateralizes to the affected ear. Sensorineural loss instead lateralizes the Weber to the better ear and preserves air conduction over bone conduction.

Question 31Behavioral Health & Nervous Systems/Special Senses

Bilateral destruction of which of the following structures produces a syndrome of hyperorality, hypersexuality, visual agnosia, and loss of fear?

  1. Mammillary bodies
  2. Hippocampus
  3. Amygdala Correct answer.
  4. Septal nuclei

Explanation

The amygdala assigns emotional salience to sensory input and mediates fear and social behavior; bilateral loss produces Klüver-Bucy syndrome. The hippocampus handles declarative memory, so its loss produces amnesia rather than this behavioral picture.

Question 32Behavioral Health & Nervous Systems/Special Senses

Which of the following features most favors major depressive disorder over uncomplicated grief?

  1. Preserved sense of self-worth despite the loss
  2. Pervasive anhedonia and worthlessness Correct answer.
  3. Tearfulness triggered by reminders of the deceased
  4. Sadness that comes in waves with periods of normal mood

Explanation

Uncomplicated grief comes in waves, is cued by reminders of the deceased, and usually spares self-esteem. Pervasive anhedonia with worthlessness, guilt, and persistent functional impairment indicates a major depressive episode.

Question 33Behavioral Health & Nervous Systems/Special Senses

Withdrawal from which of the following substances is characterized by tremor, seizures, and delirium tremens?

  1. Opioids
  2. Cannabis
  3. Cocaine
  4. Alcohol Correct answer.

Explanation

Alcohol withdrawal reflects loss of chronic GABA facilitation and NMDA antagonism, producing autonomic hyperactivity, tremor, seizures, and delirium tremens, which can be fatal. Opioid and stimulant withdrawal are distressing but not typically life-threatening in this way.

Question 34Behavioral Health & Nervous Systems/Special Senses

Which of the following is most characteristic of bulimia nervosa?

  1. Intense fear of gaining weight with low body weight
  2. Amenorrhea
  3. Recurrent binge eating followed by purging Correct answer.
  4. Body weight substantially below normal

Explanation

Bulimia nervosa is defined by recurrent episodes of binge eating with compensatory purging, and body weight is usually normal or near normal. The disorder also carries risk of hypokalemia, metabolic alkalosis, and dental enamel erosion.

Question 35Behavioral Health & Nervous Systems/Special Senses

A 24-year-old man started haloperidol 3 days ago and now has a temperature of 40°C, generalized rigidity, confusion, and a creatine kinase level of 4,000 U/L. Which of the following is the most likely diagnosis?

  1. Acute dystonic reaction
  2. Serotonin syndrome with clonus
  3. Malignant hyperthermia from anesthesia
  4. Neuroleptic malignant syndrome Correct answer.

Explanation

Neuroleptic malignant syndrome follows dopamine blockade and presents with fever, lead-pipe rigidity, altered mental status, and marked creatine kinase elevation, typically over days. Management includes stopping the agent and giving dantrolene or bromocriptine.

Question 36Behavioral Health & Nervous Systems/Special Senses

A patient taking an MAO inhibitor is given meperidine and develops agitation, hyperthermia, hyperreflexia, and inducible ankle clonus. Which of the following is the most likely cause of this presentation?

  1. Serotonin syndrome Correct answer.
  2. Neuroleptic malignant syndrome
  3. Tyramine-induced hypertensive crisis
  4. Anticholinergic toxicity

Explanation

Combining a monoamine oxidase inhibitor with a serotonergic opioid causes synaptic serotonin excess, producing the triad of mental status change, autonomic instability, and neuromuscular hyperactivity with clonus. Rigidity with bradyreflexia would instead suggest neuroleptic malignant syndrome.

Question 37Behavioral Health & Nervous Systems/Special Senses

A patient has right-sided ptosis, a dilated right pupil, and a right eye deviated down and out, together with left-sided weakness of the arm and leg. A lesion of which of the following is most likely responsible?

  1. Right pons
  2. Right midbrain Correct answer.
  3. Left medulla
  4. Right cerebellar hemisphere

Explanation

This is Weber syndrome, caused by a midbrain lesion involving the oculomotor fascicle and the cerebral peduncle. The result is ipsilateral CN III palsy with contralateral hemiparesis.

Question 38Behavioral Health & Nervous Systems/Special Senses

A patient with a stab wound to the spinal cord has lost vibration and position sense on the right below the lesion and pain and temperature sensation on the left below the lesion. Which of the following is the most likely diagnosis?

  1. Brown-Séquard syndrome Correct answer.
  2. Anterior spinal artery occlusion
  3. Syringomyelia
  4. Tabes dorsalis

Explanation

Hemisection of the cord damages the ipsilateral dorsal columns and corticospinal tract and the ipsilateral spinothalamic fibers that have already crossed, giving ipsilateral loss of vibration and position sense plus contralateral loss of pain and temperature. This combination defines Brown-Séquard syndrome.

Question 39Behavioral Health & Nervous Systems/Special Senses

Pain and temperature sensation from the trunk and limbs is conveyed to the thalamus primarily by which of the following pathways?

  1. Dorsal columns
  2. Corticospinal tract
  3. Spinothalamic tract Correct answer.
  4. Spinocerebellar tract

Explanation

Nociceptive and thermal fibers synapse in the dorsal horn, cross in the anterior white commissure, and ascend in the contralateral spinothalamic tract to the thalamus. This crossing explains the contralateral loss of pain and temperature after a cord hemisection.

Question 40Behavioral Health & Nervous Systems/Special Senses

According to Erikson, an adolescent who fails to develop a coherent sense of self may remain unable to resolve which psychosocial stage?

  1. Intimacy vs isolation
  2. Identity vs role confusion Correct answer.
  3. Industry vs inferiority
  4. Trust vs mistrust

Explanation

Erikson's fifth stage, identity versus role confusion, occurs in adolescence and centers on forming a stable self-concept. Failure to do so leaves the person ill equipped for the later stage of intimacy versus isolation.

Question 41Blood & Lymphoreticular/Immune Systems

A 24-year-old woman has a microcytic, hypochromic anemia. Which laboratory result best distinguishes iron deficiency anemia from the anemia of chronic inflammation?

  1. Low serum ferritin Correct answer.
  2. Low serum total iron-binding capacity
  3. Increased mean corpuscular volume
  4. Increased transferrin saturation

Explanation

Iron deficiency depletes body iron stores, so ferritin - the main storage protein - falls and is the most specific single test. In anemia of chronic inflammation ferritin is normal or elevated because it is an acute-phase reactant, while total iron-binding capacity falls and iron is trapped in macrophages.

Question 42Blood & Lymphoreticular/Immune Systems

Gamma-carboxylation of glutamate residues is required for the function of which group of coagulation factors?

  1. Factors XI, XII, prekallikrein, and high-molecular-weight kininogen
  2. Factors VIII, IX, XI, and XII
  3. Factors II, VII, IX, and X Correct answer.
  4. Factors I, V, VIII, and XIII

Explanation

Vitamin K is the cofactor for gamma-glutamyl carboxylase, which converts glutamate residues on factors II, VII, IX, and X (and proteins C and S) into calcium-binding gamma-carboxyglutamate. Without this modification the factors cannot assemble on phospholipid membranes.

Question 43Blood & Lymphoreticular/Immune Systems

Unfractionated heparin exerts its anticoagulant effect by which mechanism?

  1. It potentiates antithrombin-mediated inactivation of thrombin and factor Xa Correct answer.
  2. It chelates calcium and blocks assembly of the prothrombinase complex
  3. It inhibits vitamin K epoxide reductase and reduces gamma-carboxylation of factors
  4. It cleaves fibrinogen directly into degradation products that inhibit thrombin

Explanation

Heparin binds antithrombin and produces a conformational change that accelerates its inactivation of thrombin, factor Xa, and several other serine proteases. Low-molecular-weight heparin retains mainly anti-Xa activity because shorter chains cannot bridge antithrombin to thrombin.

Question 44Blood & Lymphoreticular/Immune Systems

Which immunoglobulin isotype is produced earliest in a primary humoral response and is the most efficient activator of the classical complement pathway?

  1. IgA
  2. IgE
  3. IgG
  4. IgM Correct answer.

Explanation

Naive B cells express surface IgM, and IgM is the first secreted isotype after antigen exposure. Because it is a pentamer, a single IgM molecule can bind two nearby Fc regions and trigger C1q, making it the most potent complement activator.

Question 45Blood & Lymphoreticular/Immune Systems

Auer rods seen on a bone marrow aspirate are most characteristic of which diagnosis?

  1. Acute myeloid leukemia Correct answer.
  2. Acute lymphoblastic leukemia
  3. Hodgkin lymphoma
  4. Chronic lymphocytic leukemia

Explanation

Auer rods are needle-shaped aggregates of fused primary granules that are found only in cells of the myeloid lineage, most often in acute promyelocytic leukemia. Their presence confirms a myeloblastic rather than lymphoblastic origin.

Question 46Blood & Lymphoreticular/Immune Systems

A person with blood type O carries which naturally occurring plasma antibodies?

  1. Anti-A and anti-B Correct answer.
  2. Anti-A only
  3. Neither anti-A nor anti-B
  4. Anti-B only

Explanation

Individuals form IgM antibodies against the ABO antigens they lack, generated in response to similar environmental oligosaccharides. Type O red cells express neither A nor B antigen, so the plasma contains both anti-A and anti-B.

Question 47Blood & Lymphoreticular/Immune Systems

Which metabolite is elevated in vitamin B12 deficiency but remains normal in isolated folate deficiency?

  1. Formiminoglutamic acid
  2. 5-methyltetrahydrofolate
  3. Methylmalonic acid Correct answer.
  4. Homocysteine

Explanation

Vitamin B12 is the cofactor for methylmalonyl-CoA mutase, so its deficiency causes methylmalonic acid to accumulate; folate has no role in that reaction. Homocysteine rises in both deficiencies because the methionine synthase reaction requires both B12 and 5-methyltetrahydrofolate.

Question 48Blood & Lymphoreticular/Immune Systems

In chronic inflammation, interleukin-6 stimulates the liver to release which peptide that lowers intestinal iron absorption and blocks macrophage iron export?

  1. Hepcidin Correct answer.
  2. Ferroportin
  3. Erythropoietin
  4. Transferrin

Explanation

Hepcidin binds and internalizes ferroportin on enterocytes and macrophages, trapping iron inside cells and lowering plasma iron. This is the central mechanism of the hypoferremia seen in anemia of chronic inflammation.

Question 49Blood & Lymphoreticular/Immune Systems

A man of Mediterranean descent develops jaundice and dark urine after taking primaquine. Which peripheral smear finding is most characteristic of this disorder?

  1. Schistocytes
  2. Spherocytes
  3. Bite cells Correct answer.
  4. Target cells

Explanation

Oxidant drugs overwhelm the reduced glutathione system when glucose-6-phosphate dehydrogenase is deficient, and hemoglobin precipitates as Heinz bodies. Macrophages remove these inclusions, leaving a bite-shaped defect in the red cell membrane.

Question 50Blood & Lymphoreticular/Immune Systems

A 30-year-old has chronic hemolytic anemia, splenomegaly, and pigment gallstones, and his red cells show loss of membrane surface area with no inclusions. Which test best supports the suspected diagnosis?

  1. Hemoglobin electrophoresis
  2. Flow cytometry for CD55 and CD59
  3. Osmotic fragility test Correct answer.
  4. Direct antiglobulin (Coombs) test

Explanation

Hereditary spherocytosis results from defects in vertical membrane skeleton proteins, and the poorly supported lipid bilayer loses area as cells pass through the spleen. Spherocytes are unable to swell in hypotonic saline because they already have maximal sphericity, so osmotic fragility is increased.