A young girl bleeds heavily after a dental extraction. Her platelet count is mildly low and the blood film shows giant platelets. Platelets do not aggregate with ristocetin, even when normal plasma is added. What is the diagnosis?
Answer: Bernard–Soulier (GpIb)
Bernard–Soulier syndrome is an inherited deficiency of platelet GpIb, the receptor for von Willebrand factor. Platelets cannot stick to damaged vessel walls. Features: giant platelets, mild thrombocytopenia and absent ristocetin aggregation not corrected by normal plasma.
Remember Bernard–Soulier = Big Sticky-less platelets.
Why the other options are wrong
Glanzmann (GpIIb/IIIa) Normal platelet size and count; no aggregation with ADP or collagen, but normal ristocetin response.
Von Willebrand disease Ristocetin aggregation is corrected by adding normal plasma (it supplies vWF).
Immune thrombocytopenia Platelets are low but function normally; no giant platelets with this pattern.
Haemophilia A Clotting factor problem; platelets are normal.
Question 2Medium
A 78-year-old man has had itchy, tense, fluid-filled blisters on his thighs and abdomen for a month and is otherwise well; they do not spread when pressed and his mouth is spared. Biopsy shows a split beneath the epidermis with eosinophils, and immunofluorescence shows linear IgG and C3 along the basement membrane. Which of the following structures is the target of these antibodies?
Answer: Hemidesmosomes
This is bullous pemphigoid. Hemidesmosomes anchor basal keratinocytes to the basement membrane, linking keratin filaments inside the cell to laminin and type XVII collagen outside it. Autoantibodies against hemidesmosomal proteins (BP180 and BP230) fix complement and cause separation below the epidermis, so the blister roof is the full epidermis and the blisters are tense. Desmosomes, which join keratinocytes to each other, are the target in pemphigus.
Hemidesmosomes
Join basal cell to basement membrane
Targets: BP180, BP230
Split is subepidermal: tense blisters
Nikolsky negative
Remember Pemphigoid: below the epidermis.
Exam trap Do not confuse the immunofluorescence: pemphigoid is linear at the basement membrane, pemphigus is net-like between cells.
Why the other options are wrong
Desmosomes Target in pemphigus vulgaris, which gives flaccid intraepidermal blisters.
Tight junctions Not involved in blistering skin disease.
Gap junctions Allow communication between cells; not the target.
Adherens junctions Link actin via cadherins; not the target here.
Question 3Medium
During an emergency laparotomy for a stab wound, arterial blood sprays into the left eye of an assistant who is not wearing goggles. The patient is known to have hepatitis C, and his HIV status is unknown. The assistant scrubs out. Which of the following should she do first?
Answer: Irrigate the eye with plenty of water or saline
The conjunctiva is a mucous membrane, and blood splashed onto it can transmit blood-borne viruses, though the risk is lower than after a needlestick. The first step is to irrigate the eye immediately and copiously with running water or saline, with contact lenses removed, to reduce the viral dose. Soap and antiseptics should not be put in the eye. The incident is then reported, the source assessed (with consent for HIV testing), and PEP or follow-up arranged as needed.
Mucosal splash
Irrigate at once with water or saline
No soap in the eye
Report and assess the source
Wear eye protection in theatre
Remember Splash in the eye: flush first, think later.
Exam trap Mucous membrane exposures count as significant and must be reported like needlesticks.
Why the other options are wrong
Wash the eye with soap and chlorhexidine Soap and antiseptics injure the conjunctiva.
Instil antibiotic drops and pad the eye Antibiotics do not act on viruses, and padding delays irrigation.
Start three-drug HIV PEP before anything else PEP may be needed, but irrigation comes first and takes only minutes.
Rub the eye dry with a sterile gauze Rubbing can damage the conjunctiva and does not remove blood.
Question 4Medium
A 40-year-old obese nurse completed three doses of hepatitis B vaccine, all given into the buttock at a local clinic, but her anti-HBs level is below 10 mIU/mL. Which of the following most likely explains the poor response?
Answer: Injection into fat rather than muscle
Hepatitis B vaccine is an adjuvanted recombinant HBsAg protein that must reach muscle, which is well vascularised and rich in antigen-presenting cells. Injections into the buttock, especially in obese adults, often deposit the vaccine in subcutaneous fat, where uptake and presentation are poor, so antibody responses are lower. Adults should be vaccinated in the deltoid and infants in the anterolateral thigh. Other causes of non-response include older age, smoking, obesity, immunosuppression and chronic kidney disease.
Vaccine injection sites
Adults: deltoid
Infants: anterolateral thigh
Buttock: risk of fat deposition, poor response
Also sciatic nerve risk
Remember Fat is a poor place for a vaccine.
Exam trap Rabies vaccine given into the buttock has also been linked to vaccine failure.
Why the other options are wrong
The vaccine contains live attenuated virus It is a recombinant protein vaccine, not live.
Buttock injections cause rapid antigen loss in urine Antigen is not lost in the urine.
Women respond poorly to recombinant vaccines Sex does not explain the failure.
Three doses are too few for any adult Three doses give protective levels in most adults when injected into muscle.
A carcinoma and a sarcoma of similar size behave differently in how they first spread. Which statement is generally correct?
Answer: Carcinomas spread first by lymphatics
As a general rule, carcinomas (epithelial cancers) tend to spread first through lymphatics to regional nodes, while sarcomas (mesenchymal cancers) tend to spread first through the bloodstream to the lungs. This is only a rule of thumb: carcinomas can spread by blood too, and some use both routes. Knowing the usual route guides where to look for metastasis and how to stage.
Spread routes
Carcinoma: lymphatics first
Sarcoma: bloodstream first
Rule of thumb, not absolute
Carcinoma can also spread by blood
Remember Carcinoma to nodes; sarcoma to lungs.
Exam trap These are tendencies; exceptions are common.
Why the other options are wrong
Sarcomas spread first by lymphatics Sarcomas usually spread first by blood, not lymph.
Carcinomas never reach the blood Carcinomas can reach the blood later.
Sarcomas spread only within the organ Sarcomas do spread to distant organs.
Both spread first through nerves Perineural spread occurs but is not the usual first route.
Question 6Hard
Three weeks after a difficult caesarean section with extension of the incision, a woman has sudden heavy bright red vaginal bleeding. Urine hCG is negative. Doppler ultrasound shows a 3 cm anechoic sac in the myometrium near the scar, filled with swirling flow that changes direction (a 'yin-yang' pattern), with a narrow neck to a branch of the uterine artery. What is the most likely diagnosis?
Answer: Uterine artery pseudoaneurysm
A pseudoaneurysm forms when an injured arterial wall leaks into surrounding tissue and the haematoma stays connected to the artery through a neck. It is contained only by clot and fibrous tissue, so it can rupture weeks after surgery and cause secondary postpartum haemorrhage. On Doppler it appears as a single anechoic sac with turbulent to-and-fro flow. An arteriovenous malformation shows a tangle of many vessels with high-velocity flow, retained products show echogenic tissue in the cavity, and trophoblastic tumours have a positive hCG.
Uterine artery pseudoaneurysm
Follows caesarean or curettage injury
Secondary PPH weeks later
Doppler: sac with yin-yang flow
Treat by selective embolisation
Remember Late heavy bleeding after a traumatic caesarean: check for a pseudoaneurysm.
Exam trap Secondary PPH is not always retained tissue; a negative hCG and an arterial sac point to pseudoaneurysm.
Why the other options are wrong
Retained products of conception Shows echogenic tissue in the cavity, not an anechoic sac with a neck.
Arteriovenous malformation Shows a tangle of many vessels, not a single sac.
Placental site trophoblastic tumour Usually raises hCG; here it is negative.
Endometritis with scar dehiscence Would cause fever and tenderness; no sac with arterial flow.
Question 7Medium
An Rh-negative primigravida with no previous pregnancies, miscarriages or terminations is found at booking to have a high anti-D titre, and her fetus later becomes anaemic. At 14 she had a large transfusion after a road accident. What most likely sensitised her?
Answer: Earlier transfusion of D-positive blood
Anti-D is not a naturally occurring antibody; it appears only after exposure to D-positive red cells. In a woman who has never been pregnant before, the most likely exposure is a transfusion of D-positive blood, for example in an emergency when Rh-negative blood was not available. A primary response then left memory B cells, so the D-positive fetus provoked a strong IgG response early in this pregnancy. This is why girls and women of childbearing age should receive Rh-compatible blood.
Sensitisation outside pregnancy
Anti-D is never natural
Needs exposure to D-positive cells
Transfusion is a key non-obstetric cause
Give girls Rh-compatible blood
Remember High anti-D in a first pregnancy: ask about transfusion.
Exam trap Do not assume a first pregnancy cannot be affected; ask about previous transfusion.
Why the other options are wrong
Natural anti-D present since infancy Unlike anti-A and anti-B, anti-D does not occur naturally.
Silent fetal bleed in the first trimester Early fetal bleeds are small and rarely give a high titre at booking.
Cross-reaction with her own C antigen Antibodies do not arise against a person's own antigens in this way.
Anti-D passed to her in breast milk Not a route of sensitisation.
Question 8Medium
Five weeks after an intrauterine death at 30 weeks, which she declined to have induced, a woman has bruising and a low fibrinogen. Which result best shows that fibrin has been formed in her vessels and then broken down by plasmin?
Answer: Raised D-dimer level
D-dimer is a fragment released only when plasmin breaks down fibrin that has been cross-linked by factor XIIIa. A high D-dimer therefore proves that thrombin has made fibrin in the body and that fibrinolysis has followed, which is the core of DIC. Low fibrinogen and platelets show consumption but can occur for other reasons, and a long thrombin time reflects low or abnormal fibrinogen. A retained dead fetus releases tissue factor slowly, so DIC usually appears after about four weeks.
D-dimer
Made only from cross-linked fibrin
Proves thrombin and plasmin activity
Retained dead fetus: DIC after ~4 weeks
Fibrinogen and platelets fall
Remember D-dimer means fibrin was made and broken.
Exam trap D-dimer is normally raised in pregnancy, so the trend matters more than one value.
Why the other options are wrong
Prolonged thrombin time Shows low or abnormal fibrinogen, not fibrin breakdown.
Low platelet count Shows consumption or other causes, not fibrinolysis.
Prolonged bleeding time Reflects platelet function or number, not fibrin.
Low fibrinogen level Shows consumption but not that fibrin was formed and lysed.
Question 9Medium
A year after removal of a skull base tumour, a 60-year-old man's tongue deviates to the right on protrusion, and the right half of the tongue is shrunken and soft with a sharp line at the midline. What has happened to the muscle of the right half of the tongue?
Answer: Fatty replacement of denervated muscle
Injury to the hypoglossal nerve denervates the intrinsic and extrinsic tongue muscles on that side, and the tongue deviates towards the weak side on protrusion because the healthy genioglossus pushes unopposed. In the early phase denervated muscle is oedematous. Over months it atrophies and is replaced by fat, giving a shrunken, soft hemitongue sharply limited by the midline septum. On MRI the fat makes it bright on T1, which should not be mistaken for tumour.
Denervated hemitongue
Hypoglossal injury
Tongue deviates to the weak side
Early oedema, late fatty atrophy
Sharp midline boundary
Remember Shrunken, soft half-tongue: look along CN XII.
Exam trap Fasciculation of the wasted half points to a lower motor neurone lesion, as with a nerve injury.
Why the other options are wrong
Acute oedema of denervated muscle Oedema occurs in the first weeks, not a year later, and causes swelling.
Haemorrhage into the tongue Would cause swelling and bruising, not uniform shrinkage.
Recurrent tumour in the tongue Would form a firm mass rather than a shrunken hemitongue.
Venous congestion of the tongue Would cause swelling, not atrophy.
Question 10Medium
A 32-year-old woman who had two laparotomies for a ruptured appendix and pelvic abscess now has pelvic discomfort. At laparoscopy, a multiloculated collection of clear fluid trapped by thin adhesions fills the pelvis and surrounds a normal right ovary. What is the diagnosis?
Answer: Peritoneal inclusion cyst
A peritoneal inclusion cyst (peritoneal pseudocyst) forms in premenopausal women with peritoneal adhesions from surgery, infection or endometriosis. The ovary keeps producing fluid, but the adhesions stop the peritoneum from absorbing it, so the fluid is trapped in loculated pockets that take the shape of the surrounding space. The key feature is a normal ovary lying within or at the edge of the collection. An ovarian tumour arises from the ovary and replaces normal tissue.
Peritoneal inclusion cyst
Adhesions after surgery or infection
Ovarian fluid trapped
Shape follows the pelvic space
Normal ovary inside it
Remember Fluid around a normal ovary after surgery: inclusion cyst.
Exam trap These cysts recur after drainage and can be mistaken for ovarian cancer, leading to radical surgery.
Why the other options are wrong
Mucinous cystadenoma of the ovary Arises from the ovary itself and replaces it.
Hydrosalpinx A distended fluid-filled tube separate from the ovary.
Endometrioma A chocolate-coloured cyst within the ovary.
Lymphocele Follows lymph node dissection and lies along the pelvic vessels.
Question 11Medium
At autopsy six months after a left middle cerebral artery stroke, the infarcted frontoparietal cortex has been replaced by a fluid-filled cavity and the adjacent ventricle is enlarged. What process turned the infarct into this cavity?
Answer: Digestion by microglial lysosomal enzymes
Brain infarcts undergo liquefactive necrosis. The brain has little supporting connective tissue and is rich in lipid, and dead tissue is digested by enzymes from neutrophils and especially microglia (macrophages), which fill with lipid (foamy cells). Over weeks to months the debris is removed, leaving a fluid-filled cyst lined by reactive astrocytes (gliosis). Loss of tissue pulls the ventricle towards the lesion.
Brain infarct
Liquefactive necrosis
Microglia digest debris
Ends as cyst with gliosis
Ventricle enlarges (ex vacuo)
Remember Dead brain is digested to fluid, not scar.
Exam trap The brain is the main organ where ischaemic necrosis is liquefactive.
Why the other options are wrong
Coagulative necrosis with preserved outlines This is the pattern in most solid organs, not the brain.
Caseous necrosis with granulomas Typical of tuberculosis.
Fibrous scarring by fibroblasts The brain repairs by gliosis, not fibroblast scar.
Calcification of dead neurones Calcification is unusual in adult infarcts.
Question 12Medium
A 70-year-old smoker has a 6 cm infrarenal aortic aneurysm repaired. Histology of the resected wall shows a thinned media with loss of elastic lamellae and a dense chronic inflammatory infiltrate in the adventitia. Which of the following mainly breaks down the wall?
Answer: Matrix metalloproteinases from macrophages
Atherosclerotic abdominal aortic aneurysm is driven by chronic inflammation of the wall. Macrophages and other inflammatory cells release matrix metalloproteinases (especially MMP-2 and MMP-9) that degrade elastin and collagen in the media faster than smooth muscle cells can repair them, so the wall thins and dilates. Smoking strongly increases this protease activity. Mycotic and syphilitic aneurysms have distinct infective causes, and autoantibody or complement attack is not the main mechanism.
AAA pathogenesis
Chronic inflammation of the wall
Macrophages release MMP-2, MMP-9
Loss of elastin and collagen in media
Smoking raises protease activity
Remember Too much protease, too little repair: the aorta balloons.
Exam trap Atheroma starts the process, but protease-driven medial loss is what lets the aorta dilate.
Why the other options are wrong
Complement membrane attack complex Not the main mechanism of degenerative aneurysm.
Bacterial collagenase from a mycotic focus Mycotic aneurysms are infective, often saccular, and uncommon.
Antibodies against elastin fibres No specific anti-elastin antibody drives AAA.
Endarteritis of the vasa vasorum This is the mechanism in syphilitic thoracic aortitis.
