CHEMICAL PATHOLOGY MCQs

Question 1

Alpha-fetoprotein (AFP) is most useful as a tumor marker for

Accepted Answer

Hepatocellular carcinoma and non-seminomatous germ cell tumors — AFP produced by yolk sac and fetal liver. Elevated in HCC ( 400ng/mL highly suggestive), hepatoblastoma, yolk sac tumors. Pure seminoma does NOT produce AFP. Mildly elevated in cirrhosis/hepatitis but not diagnostic alone.

Question 2

PSA is best described as

Accepted Answer

Organ-specific but NOT cancer-specific — elevated in BPH, prostatitis, and carcinoma — PSA is prostate-specific but NOT cancer-specific. Elevated in BPH, prostatitis, post-DRE, and carcinoma. Low free:total PSA ratio (<10%) favors carcinoma. High ratio ( 25%) favors BPH. Used for screening, staging, and monitoring.

Question 3

CA 19-9 is most useful as a tumor marker for

Accepted Answer

Pancreatic carcinoma — CA 19-9 elevated in pancreatic carcinoma (~80% sensitivity). Also elevated in cholangiocarcinoma, gastric, colorectal cancer. NOT useful for screening. Most valuable for monitoring treatment response and recurrence. Cannot be produced by Lewis antigen-negative individuals (5–10% of population).

Question 4

Ectopic ACTH production causing Cushing's syndrome is most commonly associated with

Accepted Answer

Small cell lung carcinoma (SCLC) — SCLC most common cause of ectopic ACTH. Features: rapidly progressive, severe hypokalemia, metabolic alkalosis, hyperpigmentation, muscle wasting — often WITHOUT classic cushingoid appearance. ACTH very high, NOT suppressed by high-dose dexamethasone. Other causes: bronchial carcinoid, medullary thyroid Ca, pancreatic NETs.

Question 5

The most common cause of hypercalcemia in hospitalized cancer patients is

Accepted Answer

PTHrP secretion causing humoral hypercalcemia of malignancy — PTHrP mimics PTH at PTH1R → hypercalcemia + hypophosphatemia. PTH itself SUPPRESSED — key distinguishing feature from primary HPT. Most common tumors: SCC lung/head/neck, renal cell, breast, bladder carcinoma.

Question 6

SIADH as a paraneoplastic syndrome is most commonly caused by

Accepted Answer

Small cell lung carcinoma (SCLC) — SCLC produces ectopic ADH → SIADH → dilutional hyponatremia + inappropriately concentrated urine. Features: hyponatremia + low serum osmolality + urine osmolality 100 mOsm/kg + euvolemia. Treatment: fluid restriction ± tolvaptan/demeclocycline.

Question 7

CEA is most useful for

Accepted Answer

Monitoring treatment response and detecting recurrence of colorectal carcinoma — CEA NOT useful for screening (low specificity — elevated in smokers, pancreatitis, IBD, cirrhosis). Most valuable post-surgery for detecting colorectal cancer recurrence. Also elevated in breast, lung, gastric, pancreatic cancers. Normal <5 ng/mL.

Question 8

Beta-hCG as a tumor marker is elevated in

Accepted Answer

Choriocarcinoma, gestational trophoblastic disease, and non-seminomatous germ cell tumors — Beta-hCG is the marker for gestational trophoblastic disease and non-seminomatous GCTs. Pure seminomas may have mildly elevated hCG (~10%) but AFP is normal. Extremely sensitive — detects tiny tumor burden. Used for diagnosis, staging, monitoring, and recurrence detection.

Question 9

Constitutional delay of growth and puberty (CDGP) is best described as

Accepted Answer

A normal variant — delayed but eventual spontaneous puberty, normal final height — Most common cause of delayed puberty in boys. Family history of late puberty typical. Bone age delayed. GnRH stimulation test shows normal LH/FSH response. Reassurance is key. Short course of low-dose testosterone can be used if causing psychological distress.

Question 10

Gonadotropin-dependent (central) precocious puberty is caused by

Accepted Answer

Premature activation of the hypothalamic-pituitary-gonadal axis with elevated LH/FSH — Central precocious puberty: premature GnRH activation → elevated LH, FSH → gonadal sex steroid production → puberty before age 8 girls, age 9 boys. Girls = mostly idiopathic. Boys more often have CNS cause (tumor, hamartoma). Treatment: GnRH agonist (leuprolide) to suppress axis.

Question 11

McCune-Albright syndrome causes gonadotropin-INDEPENDENT precocious puberty through

Accepted Answer

Gain-of-function GNAS mutations → constitutively active Gsα → autonomous sex steroid production without LH/FSH — Classic triad: precocious puberty + polyostotic fibrous dysplasia + café-au-lait spots (irregular "coast of Maine" borders). GnRH agonists do NOT work (axis not driving it). Treatment: aromatase inhibitors (girls) or testolactone.

Question 12

Kallmann syndrome is characterized by

Accepted Answer

Hypogonadotropic hypogonadism combined with anosmia due to failed GnRH neuron migration — Kallmann syndrome: KAL1 (X-linked) or FGFR1 (autosomal dominant) mutations → GnRH neurons fail to migrate from olfactory placode to hypothalamus → absent GnRH + absent olfactory bulbs → anosmia + hypogonadotropic hypogonadism. Low LH, FSH, testosterone/estrogen. Treatment: GnRH pulsatile therapy or gonadotropin replacement for fertility.

Question 13

The most common cause of hirsutism in women is

Accepted Answer

Polycystic ovary syndrome (PCOS) — PCOS causes ~70–80% of hirsutism cases. Mechanism: insulin resistance → hyperinsulinemia → increased androgen production from theca cells + decreased SHBG → elevated free testosterone → hirsutism, acne, androgenic alopecia. Rotterdam criteria (2 of 3): oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovaries on ultrasound.

Question 14

Virilism in women differs from hirsutism in that it includes

Accepted Answer

Clitoromegaly, deepening of voice, temporal balding, and muscle development — suggesting androgen-secreting tumor — Hirsutism = excess terminal hair in male-pattern distribution (mild-moderate androgen excess). Virilism = full masculinization including clitoromegaly, voice deepening, temporal balding, breast atrophy, increased muscle mass — suggests severe androgen excess from adrenal or ovarian androgen-secreting tumor. Requires urgent investigation with testosterone, DHEAS, 17-OHP.

Question 15

In semen analysis, the normal sperm count (WHO 2021 criteria) is

Accepted Answer

>16 million/mL (lower reference limit) — WHO 2021 lower reference limits: sperm concentration ≥16 million/mL, total motility ≥42%, progressive motility ≥30%, normal morphology ≥4% (Kruger strict criteria). Azoospermia = no sperm. Oligozoospermia = <16 million/mL. Asthenozoospermia = poor motility. Teratozoospermia = abnormal morphology.

Question 16

Turner syndrome (45,X) causes infertility because of

Accepted Answer

Premature ovarian failure — streak gonads → primary amenorrhea + elevated FSH/LH — Turner syndrome: 45,X (or mosaic). Streak gonads (fibrous tissue replacing ovaries) → no estrogen/progesterone → no negative feedback → elevated FSH and LH (hypergonadotropic hypogonadism). Features: short stature, webbed neck, shield chest, coarctation of aorta, horseshoe kidney. Requires estrogen replacement for puberty induction and bone protection.

Question 17

Therapeutic drug monitoring (TDM) is most important for drugs with

Accepted Answer

Narrow therapeutic index where small dose changes cause toxicity or treatment failure — TDM is indicated for: narrow therapeutic index drugs (digoxin, lithium, phenytoin, gentamicin, vancomycin, cyclosporine, theophylline), drugs with unpredictable pharmacokinetics, drugs where toxicity mimics the disease being treated, monitoring compliance, and dose adjustment in renal/hepatic failure.

Question 18

Digoxin toxicity is characterized by

Accepted Answer

Xanthopsia (yellow vision), nausea, bradycardia, heart block, and ventricular arrhythmias — Digoxin toxicity features: GI (nausea, vomiting, anorexia), CNS (xanthopsia — yellow-green visual disturbance, confusion), cardiac (bradycardia, AV block, ventricular arrhythmias — PAT with block is classic). Hypokalemia WORSENS toxicity (K+ and digoxin compete for same Na/K ATPase binding site). Therapeutic range: 0.5–2.0 ng/mL.

Question 19

Lithium toxicity is precipitated by

Accepted Answer

Dehydration, sodium depletion, NSAIDs, and thiazide diuretics — all increase lithium reabsorption — Lithium is reabsorbed in proximal tubule alongside sodium. Anything that depletes sodium → kidney conserves sodium AND lithium → toxicity. Precipitants: dehydration, low-salt diet, NSAIDs (reduce GFR), thiazides (increase proximal reabsorption), ACE inhibitors. Therapeutic range: 0.6–1.2 mmol/L. Toxicity: tremor, ataxia, confusion, seizures, cardiac arrhythmias.

Question 20

Paracetamol (acetaminophen) overdose causes hepatotoxicity through

Accepted Answer

Saturation of glucuronidation/sulfation → excess NAPQI production → glutathione depletion → hepatocyte necrosis — Normal: paracetamol metabolized by glucuronidation/sulfation (safe). Small amount via CYP2E1 → NAPQI (toxic) → immediately detoxified by glutathione. Overdose: glucuronidation saturated → more NAPQI → glutathione depleted → NAPQI binds hepatocyte proteins → centrilobular necrosis. Treatment: N-acetylcysteine (NAC) replenishes glutathione. Nomogram used to guide treatment.

Question 21

Salicylate (aspirin) overdose characteristically causes

Accepted Answer

Early respiratory alkalosis followed by high anion gap metabolic acidosis — Salicylates: directly stimulate respiratory center → hyperventilation → respiratory alkalosis (early). Then: uncouple oxidative phosphorylation → lactic acidosis + ketoacidosis → HAGMA (late). In children: metabolic acidosis often predominates. Features: tinnitus, hyperventilation, hyperthermia, confusion. Treatment: urinary alkalinization (sodium bicarbonate) → increases ionized salicylate in urine → traps it → enhances excretion.

Question 22

Carbon monoxide (CO) poisoning causes toxicity by

Accepted Answer

Binding hemoglobin with 240× greater affinity than O2 → carboxyhemoglobin → functional anemia + tissue hypoxia — CO binds Hb → carboxyhemoglobin (COHb) → reduces O2-carrying capacity + shifts O2 dissociation curve LEFT (Hb holds O2 more tightly → less O2 delivered to tissues). Also inhibits cytochrome oxidase directly. Pulse oximetry FALSELY NORMAL (cannot distinguish COHb from oxyHb). Diagnosis: co-oximetry. Treatment: 100% O2 (shortens COHb half-life from 5hrs to 60–90min) ± hyperbaric O2.

Question 23

The antidote for organophosphate poisoning is

Accepted Answer

Atropine + pralidoxime (2-PAM) — Organophosphates irreversibly inhibit acetylcholinesterase → ACh accumulates → cholinergic toxidrome: SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis) + bradycardia, miosis, bronchospasm, muscle fasciculations → paralysis. Atropine: blocks muscarinic effects. Pralidoxime (2-PAM): reactivates acetylcholinesterase i [... middle excerpt for long-note safety ...] cessive. Phenylalanine → normally converted to tyrosine (requires phenylalanine hydroxylase + BH4 cofactor). Blocked → phenylalanine accumulates → phenylpyruvate/phenylacetate in urine (musty/mousy odor). Decreased melanin → fair skin/hair/eyes. Detected on newborn screening (Guthrie test). Treatment: phenylalanine-restricted diet + sapropterin (BH4 analogue) in responsive cases. Start IMMEDIATELY to prevent intellectual disability.

Question 24

Phenylketonuria (PKU) is caused by deficiency of

Accepted Answer

Phenylalanine hydroxylase — Phenylalanine hydroxylase deficiency → phenylalanine accumulates to neurotoxic levels. Autosomal recessive. Phenylalanine → normally converted to tyrosine (requires phenylalanine hydroxylase + BH4 cofactor). Blocked → phenylalanine accumulates → phenylpyruvate/phenylacetate in urine (musty/mousy odor). Decreased melanin → fair skin/hair/eyes. Detected on newborn screening (Guthrie test). Treatment: phenylalanine-restricted diet + sapropterin (BH4 analogue) in responsive cases. Start IMMEDIATELY to prevent intellectual disability.

Question 25

Maple syrup urine disease (MSUD) is caused by

Accepted Answer

Deficiency of branched-chain alpha-ketoacid dehydrogenase → accumulation of leucine, isoleucine, valine — Autosomal recessive. Branched-chain amino acids (leucine, isoleucine, valine) accumulate → maple syrup odor of urine/cerumen. Leucine is most neurotoxic. Presents neonatally: poor feeding, vomiting, lethargy → cerebral edema → death if untreated. Treatment: BCAA-restricted diet + thiamine supplementation (some responsive). Leucine levels monitored closely.

Question 26

Homocystinuria (classical) is caused by deficiency of

Accepted Answer

Cystathionine beta-synthase → homocysteine accumulates — CBS deficiency → homocysteine + methionine accumulate. Features resemble Marfan syndrome (tall, long limbs, lens subluxation — but DOWNWARD in homocystinuria vs UPWARD in Marfan). Plus: intellectual disability, osteoporosis, THROMBOEMBOLISM (homocysteine damages endothelium). Treatment: B6 (pyridoxine) in responsive cases + low-methionine diet + betaine + B12/folate.

Question 27

Alkaptonuria (ochronosis) is caused by deficiency of

Accepted Answer

Homogentisate oxidase → homogentisic acid accumulates → deposits in connective tissue — Autosomal recessive. Homogentisic acid (HGA) accumulates → oxidizes and polymerizes → ochronosis (blue-black pigmentation of connective tissue: ear cartilage, sclerae, tendons). Urine turns dark on standing (oxidation of HGA). Complications: ochronotic arthropathy (spine, large joints), cardiac valve involvement. Benign in childhood, symptomatic in adulthood. Treatment: low protein diet + nitisinone (blocks HGA production).

Question 28

Galactosemia (classical) is caused by deficiency of

Accepted Answer

Galactose-1-phosphate uridylyltransferase (GALT) → galactose-1-phosphate accumulation → liver, brain, kidney damage — GALT deficiency → galactose-1-phosphate accumulates (toxic). Presents in neonates after milk feeding: jaundice, hepatomegaly, cataracts (galactitol in lens), intellectual disability, E. coli sepsis (particularly susceptible). Newborn screening: positive Beutler test. Treatment: immediate galactose/lactose-free diet. Note: galactokinase deficiency (milder) causes cataracts only.

Question 29

Osteoporosis is defined as

Accepted Answer

Bone mineral density T-score ≤ −2.5 at hip or lumbar spine (WHO definition) — WHO definition: T-score compares BMD to young adult mean. Normal: T ≥ −1.0. Osteopenia: −1.0 to −2.5. Osteoporosis: ≤ −2.5. Severe osteoporosis: ≤ −2.5 + fragility fracture. DEXA scan is gold standard. FRAX tool calculates 10-year fracture probability. Treatment: bisphosphonates (alendronate), denosumab, teriparatide (severe cases).

Question 30

Osteomalacia in adults (rickets in children) is caused by

Accepted Answer

Vitamin D deficiency or phosphate wasting → defective bone mineralization → soft bones — Osteomalacia: inadequate mineralization of osteoid (bone matrix laid down but not calcified). Causes: vitamin D deficiency (most common), malabsorption, renal disease (impaired 1-alpha hydroxylation), phenytoin (accelerates vitamin D catabolism), X-linked hypophosphatemia (FGF23 excess). Features: bone pain, muscle weakness, waddling gait, Looser's zones (pseudofractures) on X-ray. Biochem: low Ca, low PO4, high ALP, high PTH, low 25-OH-vitamin D.

Question 31

Paget's disease of bone is characterized by

Accepted Answer

Disordered bone remodeling — excessive osteoclast activity followed by disorganized osteoblast activity → enlarged, deformed,… — Paget's: paramyxovirus implicated. Phases: osteolytic (osteoclast excess) → mixed → osteosclerotic. Characteristic histology: mosaic/jigsaw pattern of lamellar bone. Markedly elevated ALP (bone formation marker). Features: bone pain, skull enlargement (hat size increase), bowing of tibia (saber shin), deafness (CN VIII compression), high-output cardiac failure (increased vascularity). Complications: osteosarcoma (<1%). Treatment: bisphosphonates.

Question 32

In gout, monosodium urate crystal deposition is most commonly seen in the

Accepted Answer

First metatarsophalangeal joint (podagra) — Gout = inflammatory arthritis due to monosodium urate crystal deposition. Hyperuricemia is a prerequisite but not diagnostic. Most common site: first MTP joint (podagra). Other sites: knees, ankles, wrists, elbows. Tophi (urate deposits in soft tissues). Diagnosis: needle-shaped, negatively birefringent crystals in synovial fluid. Treatment: acute attack (NSAIDs, colchicine, steroids); prophylaxis (allopurinol, febuxostat, probenecid).

Question 33

Which of the following causes a HIGH anion gap metabolic acidosis (HAGMA)?

Accepted Answer

Lactic acidosis (e.g., sepsis, hypoperfusion) — HAGMA = MUDPILES (Methanol, Uremia, DKA, Paraldehyde, Iron/Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates). Normal anion gap metabolic acidosis (NAGMA) = used to be HARDASS (Hyperalimentation, Addison's, RTA, Diarrhea, Acetazolamide, Spironolactone, Saline). Diarrhea and RTA are NAGMA. Saline infusion causes hyperchloremic NAGMA.

Question 34

The most common cause of chronic kidney disease (CKD) in developed countries is

Accepted Answer

Diabetes mellitus — Diabetes (diabetic nephropathy) is the leading cause of CKD, followed by hypertension. Both contribute significantly to end-stage renal disease (ESRD). Early detection and management of diabetes and hypertension are critical for CKD prevention.

Question 35

Which of the following is most indicative of acute kidney injury (AKI)?

Accepted Answer

Rapid decline in GFR, leading to accumulation of nitrogenous waste (e.g., sudden increase in creatinine by >0.3 mg/dL or 50%… — AKI is defined by a rapid decrease in kidney function over hours to days, characterized by an increase in serum creatinine or a decrease in urine output. KDIGO criteria: creatinine increase ≥0.3 mg/dL within 48h, or creatinine increase ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/h for 6 hours.

Question 36

A dipstick test showing 3+ protein and 2+ blood, with microscopic hematuria and red cell casts, strongly suggests

Accepted Answer

Glomerulonephritis — Red cell casts are pathognomonic for glomerulonephritis (inflammation of the glomeruli), indicating glomerular bleeding. Proteinuria is also typical for glomerular damage. Prerenal azotemia would have minimal protein/blood. UTI would show WBCs and bacteria, usually without casts. Postrenal obstruction might have blood but not red cell casts (unless there's superimposed GN).

Question 37

The most common type of renal stone is

Accepted Answer

Calcium oxalate — Calcium oxalate stones are the most common (70–80%). Causes: hypercalciuria (idiopathic), hyperoxaluria. Uric acid stones (5–10%) associated with gout/hyperuricemia, acidic urine. Struvite stones (10–15%) associated with UTI by urease-producing bacteria (Proteus, Klebsiella), staghorn calculi. Cystine stones (1–2%) due to inherited defect in amino acid transport.

Question 38

The most appropriate initial diagnostic test for suspected renal artery stenosis (RAS) is

Accepted Answer

Renal biopsy — Renal ultrasound with Doppler is a common first-line screening test due to its non-invasiveness, though its sensitivity/specificity are operator-dependent. CT angiography and MR angiography are more definitive non-invasive tests. Angiography is the gold standard but invasive. RAS should be suspected in sudden onset or refractory hypertension, especially with unexplained AKI after starting ACEi/ARB, or asymmetric kidney size.

Question 39

The C-peptide level is useful in distinguishing between type 1 and type 2 diabetes because

Accepted Answer

It is co-secreted with insulin, so reflects endogenous insulin production (low in type 1, variable/normal/high in type 2) — C-peptide is a byproduct of proinsulin cleavage, equimolarly secreted with insulin. Therefore, C-peptide levels reflect endogenous insulin production. In Type 1 DM, beta cells are destroyed, so insulin and C-peptide are very low or undetectable. In Type 2 DM, there is insulin resistance and often initial hyperinsulinemia, so C-peptide can be normal or high, decreasing over time.

Question 40

The Somogyi effect differs from the dawn phenomenon in that

Accepted Answer

The Somogyi effect = nocturnal hypoglycemia → counter-regulatory hormone rebound → morning hyperglycemia (manage by reducing… — Somogyi effect: excess insulin → nocturnal hypoglycemia → counter-regulatory response (glucagon, adrenaline, GH, cortisol) → rebound morning hyperglycemia. Management: reduce evening insulin dose. Dawn phenomenon: overnight GH/cortisol surges → hepatic glucose output → morning hyperglycemia WITHOUT prior nocturnal hypoglycemia. Management: increase evening insulin or use longer-acting insulin. Distinguish by continuous glucose monitoring or 3am blood glucose check.

Question 41

The polyol pathway in diabetic complications involves

Accepted Answer

Aldose reductase converting excess glucose to sorbitol → osmotic damage to cells (lens, nerves, kidneys) — Four key mechanisms of diabetic microvascular complications: (1) Polyol pathway — sorbitol accumulation (lens → cataracts, nerves → neuropathy). (2) AGEs — glycation of proteins/vessels. (3) PKC activation — vascular permeability, angiogenesis. (4) Hexosamine pathway. Aldose reductase inhibitors (e.g. epalrestat) target the polyol pathway. Know all four mechanisms for exams.

Question 42

The dexamethasone suppression test distinguishes causes of Cushing's syndrome. Which result pattern confirms ectopic ACTH syndrome?

Accepted Answer

Cortisol NOT suppressed by either low-dose or high-dose dexamethasone, with very high ACTH — Ectopic ACTH: very high ACTH (often 200 pg/mL) + cortisol not suppressed by any dose of dexamethasone. Primary adrenal tumor: ACTH undetectable (suppressed by high cortisol) + cortisol not suppressed. Cushing's disease (pituitary adenoma): not suppressed by low-dose but suppressed by high-dose. Normal: suppressed by low-dose.

Question 43

The biochemical hallmark of primary hyperaldosteronism (Conn's syndrome) is

Accepted Answer

Low renin, high aldosterone, and elevated aldosterone:renin ratio (ARR >30) — ARR (aldosterone:renin ratio) is the best screening test for primary hyperaldosteronism. ARR 30 (with aldosterone 15 ng/dL) = positive screen → confirm with salt loading test or fludrocortisone suppression test → adrenal CT → adrenal vein sampling (to distinguish unilateral adenoma from bilateral hyperplasia). Unilateral adenoma → surgery. Bilateral hyperplasia → spironolactone/eplerenone.

Question 44

11-beta-hydroxylase deficiency (CAH variant) differs from 21-hydroxylase deficiency in that

Accepted Answer

It causes hypertension due to accumulation of 11-deoxycorticosterone (a mineralocorticoid) — 11β-hydroxylase deficiency (~5% of CAH): blocks conversion of 11-deoxycortisol → cortisol AND 11-deoxycorticosterone → corticosterone. DOC (11-deoxycorticosterone) accumulates → potent mineralocorticoid effect → HYPERTENSION + hypokalemia (unlike 21-hydroxylase which causes salt wasting). Both: elevated androgens → virilization in females, elevated 17-OHP (11-beta) or 17-OHP + DOC.

Question 45

Acute intermittent porphyria (AIP) presents with the classic triad of

Accepted Answer

Abdominal pain, neuropsychiatric symptoms, and dark urine — WITHOUT skin involvement — AIP: porphobilinogen deaminase deficiency → ALA and PBG accumulate. No photosensitivity (porphyrins don't accumulate in skin). Precipitants: alcohol, OCP, barbiturates, sulfonamides, fasting, infection. Urine turns dark/port-wine on standing. Diagnosis: elevated urine PBG during attack. Treatment: IV hemin (heme arginate) + IV glucose (suppresses ALA synthase) + avoid triggers.

Question 46

Porphyria cutanea tarda (PCT) differs from AIP in that it presents with

Accepted Answer

Blistering photosensitive skin lesions, skin fragility, and hypertrichosis on sun-exposed areas — NO neurological features — PCT: uroporphyrinogen decarboxylase deficiency → uroporphyrin accumulates in skin → photosensitivity, blistering, skin fragility, hypertrichosis, hyperpigmentation. Associated with: alcohol, hepatitis C, HIV, hemochromatosis (HFE mutations), estrogens. Urine fluoresces pink/red under Wood's lamp. Treatment: phlebotomy (removes iron which inhibits enzyme) + chloroquine (chelates porphyrins).

Question 47

Erythropoietic protoporphyria (EPP) presents with

Accepted Answer

Immediate painful photosensitivity (burning, stinging) without blistering — unlike PCT — EPP: ferrochelatase deficiency → protoporphyrin accumulates in RBCs and skin. Immediate painful photosensitivity (within minutes of sun exposure) — burning, stinging, erythema. Characteristically NO blistering (unlike PCT). Can cause liver disease from protoporphyrin accumulation. Treatment: afamelanotide (alpha-MSH analogue → increases skin melanin), beta-carotene, sun avoidance.

Question 48

The enzyme deficient in all acute porphyrias that leads to ALA accumulation when induced is

Accepted Answer

ALA synthase 1 (ALAS1) — which is actually UPREGULATED, driving excess ALA production — In acute porphyrias, the specific enzyme block causes heme deficiency → derepresses ALAS1 (the rate-limiting enzyme) → ALAS1 upregulated → excess ALA (delta-aminolevulinic acid) produced → accumulates proximal to block → neurotoxicity. Drugs/hormones that induce CYP450 also induce ALAS1 → precipitate attacks. Hemin and glucose SUPPRESS ALAS1 → treat/prevent attacks.

Question 49

Lead poisoning causes a porphyria-like syndrome by inhibiting

Accepted Answer

ALA dehydratase AND ferrochelatase → ALA accumulates + zinc protoporphyrin (ZPP) accumulates in RBCs — Lead inhibits two enzymes: ALA dehydratase (early in pathway) → ALA accumulates (similar to AIP — can cause abdominal pain + neurological features) AND ferrochelatase (late) → zinc incorporated instead of iron → elevated ZPP in RBCs (useful screening test). Also causes: microcytic anaemia (basophilic stippling), encephalopathy, peripheral neuropathy (wrist/foot drop), renal tubular dysfunction (Fanconi syndrome). Treatment: chelation with DMSA or EDTA.

CHEMICAL PATHOLOGY MCQs

Questions, Answers & Explanations