Hormones, signal transduction and immunochemistry

17 NEET-PG practice questions on Hormones, signal transduction and immunochemistry, part of Biochemistry. The first 17 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Medium

   Notes on immunoglobulins in a child under evaluation for recurrent infections: 1. IgM is a pentamer and the most efficient activator of classical complement. 2. IgG crosses the placenta through the neonatal Fc receptor. 3. IgD is the main antibody in breast milk. 4. IgE binds mast cells through the high-affinity Fc-epsilon RI. Which statements are correct?

   1. A1, 2 and 4 only
   2. B1, 2, 3 and 4
   3. C1 and 3 only
   4. D2, 3 and 4 only

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   Answer: A · 1, 2 and 4 only

   IgM is a pentamer with a J chain and fixes complement most efficiently, as one molecule can bind C1q. IgG is carried across the placenta by FcRn. Secretory IgA, not IgD, is the main antibody in milk and secretions; IgD acts mainly as a B-cell surface receptor. IgE binds Fc-epsilon RI on mast cells and basophils, and allergen cross-linking releases histamine. Key point: IgM fixes complement best, IgG crosses the placenta, IgA is in secretions and milk, IgE binds mast cells.

   • B: Statement 3 is false, so all four cannot be correct.
   • C: Statement 3 is false (milk contains IgA), and statements 2 and 4 are true.
   • D: Statement 3 is false: IgA, not IgD, is the main antibody in milk.

2. Question 2 · Hard

   Thyroid results that do not fit are referred to the endocrine clinic for a schoolteacher of 30 with a small diffuse goitre and a resting pulse of 92/min, but no weight loss, tremor or eye signs: free T4 3.4 ng/dL (0.9-1.7), free T3 7.8 pg/mL (2.3-4.2) and TSH 3.6 mIU/L (0.4-4.5). Repeat tests on a different assay platform give the same values. Her father and younger brother have similar results. MRI of the pituitary is normal, and the serum alpha-subunit is not raised; TSH rises normally after TRH. Which defect most likely explains her results?

   1. ATSH-secreting pituitary adenoma
   2. BGraves disease with TSH-receptor antibodies
   3. CAntibodies interfering with the assay
   4. DMutation of thyroid hormone receptor beta

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   Answer: D · Mutation of thyroid hormone receptor beta

   High free T4 and T3 with a non-suppressed TSH means either a TSH-secreting adenoma or resistance to thyroid hormone. A familial pattern, normal pituitary MRI, normal alpha-subunit and a preserved TSH response to TRH point to resistance, usually from autosomal dominant, dominant-negative mutations of THRB. The beta receptor is a nuclear receptor that binds T3 and acts on thyroid response elements; the pituitary and liver depend on it, while the heart uses mainly the alpha receptor, which explains the tachycardia. Antithyroid drugs and ablation are inappropriate. Key point: Raised free T4 and T3 with normal TSH, familial, normal MRI and alpha-subunit: resistance to thyroid hormone (THRB mutation).

   • A: A TSH-oma is usually sporadic, with a visible adenoma, a raised alpha-subunit and a blunted TRH response.
   • B: Graves disease suppresses TSH to undetectable levels.
   • C: Assay interference is excluded by identical results on another platform and in relatives.

3. Question 3 · Medium

   Haemoglobin is 19.2 g/dL in a man with itching after hot baths, splenomegaly and portal vein thrombosis; serum erythropoietin is low. A mutation in which signalling molecule is most likely?

   1. ACalreticulin chaperone
   2. BBCR-ABL fusion kinase
   3. CVon Hippel-Lindau protein
   4. DJAK2 tyrosine kinase

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   Answer: D · JAK2 tyrosine kinase

   Erythrocytosis with low erythropoietin, aquagenic pruritus, splenomegaly and splanchnic thrombosis is polycythaemia vera. Over 95% of cases carry JAK2 V617F (or an exon 12 mutation), which keeps the JAK2 kinase linked to the EPO receptor active, so erythroid cells grow without erythropoietin through STAT5 signalling. Ruxolitinib inhibits JAK1 and JAK2. Key point: Polycythaemia vera with low EPO is driven by JAK2 V617F, which activates JAK-STAT signalling without EPO.

   • A: Calreticulin mutations occur in essential thrombocythaemia and myelofibrosis, not PV.
   • B: BCR-ABL defines chronic myeloid leukaemia.
   • C: VHL mutations raise HIF and erythropoietin, so EPO would be high.

4. Question 4 · Easy

   Cord blood IgM is clearly raised in a small-for-dates newborn with hepatosplenomegaly. What does this most suggest?

   1. ARh isoimmunisation
   2. BTransfer of maternal antibody
   3. CNormal neonatal immunity
   4. DIntrauterine infection of the fetus

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   Answer: D · Intrauterine infection of the fetus

   IgM does not cross the placenta, so IgM in cord blood is made by the fetus itself, which can produce it from about 20 weeks when stimulated by antigen. A raised cord IgM therefore points to intrauterine infection such as rubella, CMV, toxoplasmosis or syphilis, and pathogen-specific IgM identifies the agent. Maternal IgG crosses the placenta and only reflects the mother's immunity. Key point: IgM does not cross the placenta; a raised cord IgM means fetal infection (TORCH).

   • A: Rh disease is caused by maternal IgG anti-D, not fetal IgM.
   • B: Antibody transferred from the mother is IgG, not IgM.
   • C: Normal newborns have very low IgM at birth.

5. Question 5 · Easy

   Ring sideroblasts are seen in the marrow of a man taking isoniazid for pulmonary TB without pyridoxine; he has microcytic anaemia with a raised serum iron. Which enzyme of haem synthesis is affected?

   1. AALA synthase
   2. BFerrochelatase
   3. CALA dehydratase
   4. DUroporphyrinogen III synthase

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   Answer: A · ALA synthase

   ALA synthase, the first and rate-limiting enzyme of haem synthesis in mitochondria, needs pyridoxal phosphate. Isoniazid forms a complex with pyridoxine and depletes it, so haem synthesis falls; iron that cannot be used builds up in mitochondria around the nucleus, forming ring sideroblasts. Pyridoxine supplements prevent this. Key point: ALA synthase needs pyridoxal phosphate; isoniazid-induced B6 deficiency causes sideroblastic anaemia.

   • B: Ferrochelatase is inhibited by lead and deficient in erythropoietic protoporphyria.
   • C: ALA dehydratase is inhibited by lead and does not need pyridoxal phosphate.
   • D: Uroporphyrinogen III synthase deficiency causes congenital erythropoietic porphyria.

6. Question 6 · Medium

   Primary amenorrhoea brings a tall 17-year-old girl with well-developed breasts, scanty pubic and axillary hair and a blind-ending vagina to the gynaecology OPD. Ultrasound shows no uterus, with gonads in both inguinal canals. Karyotype is 46,XY; serum testosterone and LH are high. Her maternal aunt had the same problem. Where is the defect?

   1. AAnti-Mullerian hormone receptor
   2. BLH receptor on Leydig cells
   3. C5-alpha reductase type 2
   4. DIntracellular androgen receptor

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7. Question 7 · Medium

   Receptors and their G-protein pathways are reviewed before a pharmacology viva: 1. Alpha-1 adrenergic receptor on vascular smooth muscle. 2. V2 vasopressin receptor in the collecting duct. 3. M3 muscarinic receptor in the bladder detrusor. 4. H2 histamine receptor on gastric parietal cells. Which of these act through Gq, IP3 and calcium?

   1. A1, 2, 3 and 4
   2. B2 and 4 only
   3. C1, 3 and 4 only
   4. D1 and 3 only

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8. Question 8 · Hard

   Vaginal bleeding at 4 years, large irregular cafe-au-lait patches that stop at the midline, and a limp from fibrous dysplasia of the femur bring a girl to the paediatric endocrine clinic; LH and FSH are suppressed. Which molecular change is responsible?

   1. AMosaic activating GNAS mutation blocking GTPase
   2. BGermline inactivating GNAS mutation
   3. CActivating mutation of the LH receptor
   4. DLoss of NF1 neurofibromin

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9. Question 9 · Medium

   Rice-water stools of up to 15 litres a day are passed by a fisherman admitted to a Kolkata hospital during an outbreak; dark-field microscopy of the stool shows darting motile curved rods. He is severely dehydrated, with sunken eyes and a BP of 80/50 mmHg. How does the bacterial toxin cause this diarrhoea?

   1. AIt inactivates elongation factor 2
   2. BIt activates guanylyl cyclase, raising cGMP
   3. CIt ADP-ribosylates Gs alpha, keeping cAMP high
   4. DIt ADP-ribosylates Gi alpha, blocking inhibition

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10. Question 10 · Medium

    After a meal, insulin binds its receptor on the skeletal muscle of a healthy volunteer, and glucose uptake into the muscle rises within minutes. Which signalling route moves GLUT4 transporters to the cell membrane?

    1. AGs, adenylyl cyclase and PKA
    2. BIRS-1, PI3-kinase and Akt
    3. CJAK2 and STAT5
    4. DGq, phospholipase C and PKC

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11. Question 11 · Hard

    Laboratory results of a girl of 11 referred for short stature and episodes of tetany: serum calcium 6.8 mg/dL (8.5-10.5), phosphate 7.4 mg/dL (2.5-4.5), PTH 410 pg/mL (15-65), with normal creatinine and magnesium and a 25-hydroxyvitamin D of 32 ng/mL. She is obese, with a round face and short fourth and fifth metacarpals, and also has a raised TSH with negative thyroid antibodies. She takes no medication, and both parents are of normal height and build. An infusion of PTH fails to raise urinary cyclic AMP. A defect in which protein is most likely?

    1. APTH receptor type 1
    2. BGs alpha subunit (GNAS)
    3. CCalcium-sensing receptor
    4. DVitamin D 1-alpha-hydroxylase

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12. Question 12 · Medium

    Serum protein electrophoresis of a man with alcohol-related cirrhosis shows a low albumin and a broad rise in gamma globulin that merges with the beta band, so the normal dip between them is lost. Total protein is 7.8 g/dL, and ultrasound shows a small nodular liver. Which immunoglobulin rise chiefly causes this beta-gamma bridging?

    1. APolyclonal IgE
    2. BMonoclonal IgG
    3. CPolyclonal IgA
    4. DMonoclonal IgM

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13. Question 13 · Hard

    A haematology referral concerns a young man who neither drinks alcohol nor takes regular drugs. He has microcytic anaemia (Hb 8.4 g/dL, MCV 66 fL), serum ferritin of 900 ng/mL and a transferrin saturation of 78%. Haemoglobin HPLC is normal, and blood lead and serum copper are normal. The bone marrow shows ring sideroblasts in over 30% of erythroblasts. His maternal uncle had a similar anaemia from childhood. There is no family history of thalassaemia, and his liver is palpable 3 cm below the costal margin. Which treatment should be tried first?

    1. AHydroxyurea
    2. BOral ferrous sulfate
    3. CRegular transfusions alone
    4. DOral pyridoxine

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14. Question 14 · Medium

    In the coronary care unit, a man who took sildenafil for erectile dysfunction that evening is given sublingual nitroglycerin for angina and collapses with BP 70/40 mmHg. Both drugs act on one second messenger. Which mechanism explains the collapse?

    1. ANitrate raises cAMP; sildenafil blocks PDE3
    2. BBoth drugs block alpha-1 receptors in veins
    3. CNitrate raises cGMP; sildenafil stops its breakdown
    4. DBoth drugs block L-type calcium channels

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15. Question 15 · Easy

    During her first blood transfusion, a woman who has had frequent sinusitis, chest infections and Giardia diarrhoea develops urticaria, wheeze and hypotension within minutes. Her serum IgG and IgM levels are normal. Which immunoglobulin is most likely absent?

    1. AIgD
    2. BIgE
    3. CIgA
    4. DIgG2 subclass

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16. Question 16 · Easy

    Glucagon raises hepatic glucose output mainly through which second messenger?

    1. ACyclic GMP
    2. BTyrosine kinase cascade
    3. CCyclic AMP
    4. DIP3 and calcium

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17. Question 17 · Medium

    Urine dipstick for protein is negative in a man with back pain, anaemia (Hb 8.6 g/dL), serum calcium 11.8 mg/dL and creatinine 2.6 mg/dL, yet his 24-hour urine protein is 3.2 g. Serum free kappa light chains are 1,240 mg/L with a high kappa:lambda ratio. Why does the dipstick miss his proteinuria?

    1. ADipstick pads detect albumin, not light chains
    2. BLight chains are too large to be filtered
    3. CHypercalcaemia interferes with the dipstick
    4. DLight chains are destroyed at urine pH

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