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Flashcards in Pathology Deck (111):
1

What does this blood gas show?

pH 6.9
H+ 126nmol/L
pCO2 3.0kPa
pO2 24.0kPa
HCO3 6mmol/L

A) Normal
B) Metabolic acidosis
C) Metabolic alkalosis
D) Acute respiratory acidosis
E) Chronic respiratory acidosis
F) Respiratory alkalosis
G) Mixed metabolic and respiratory acidosis
H) Mixed metabolic and respiratory alkalosis

B - Compensated metabolic acidosis

Could be due to:
Increased H+ production (DKA, lactic acidosis)
Decreased H+ excretion (renal failure)
Loss of bicarbonate (fistula)

2

What does this blood gas show?

pH 7.55
H+ 28nmol/L
pCO2 8.2kPa
pO2 10.0kPa
HCO3 51mmol/L

A) Normal
B) Metabolic acidosis
C) Metabolic alkalosis
D) Acute respiratory acidosis
E) Chronic respiratory acidosis
F) Respiratory alkalosis
G) Mixed metabolic and respiratory acidosis
H) Mixed metabolic and respiratory alkalosis

C - Compensated metabolic alkalosis

Could be due to:
Hypokalaemia (e.g. vomiting)
H+ loss (e.g. pyloric stenosis)
Ingestion of bicarbonate

3

What does this blood gas show?

pH 7.55
H+ 28nmol/L
pCO2 3.0kPa
pO2 14.4kPa
HCO3 20mmol/L

A) Normal
B) Metabolic acidosis
C) Metabolic alkalosis
D) Acute respiratory acidosis
E) Chronic respiratory acidosis
F) Respiratory alkalosis
G) Mixed metabolic and respiratory acidosis
H) Mixed metabolic and respiratory alkalosis

F - Acute respiratory alkalosis

4

What does this blood gas show?

pH 7.41
H+ 39nmol/L
pCO2 10.4kPa
pO2 7.8kPa
HCO3 47mmol/L

A) Normal
B) Metabolic acidosis
C) Metabolic alkalosis
D) Acute respiratory acidosis
E) Chronic respiratory acidosis
F) Respiratory alkalosis
G) Mixed metabolic and respiratory acidosis
H) Mixed metabolic and respiratory alkalosis

E - Chronic respiratory acidosis (e.g. COPD)

OR

C - Metabolic alkalosis (e.g. hypokalaemia)

Need clinical picture to tell difference.

5

During acute porphyrias, what is the most useful sample to send?

A) Blood
B) CSF
C) Urine
D) Muscle biopsy
E) Stool
F) Skin biopsy

C

Urine PBG should be sent to confirm porphyria. Then further enzymes studies can be done.

6

A 22-year-old female presents with tonic-clinic seizures, blurred vision, and flashing lights. This started on returning to the UK from a holiday during which she reports drinking heavily. Other symptoms include abdominal pain, nausea and vomiting, and paranoia. You suspect a porphyria. Which is the most likely cause?

A) Porphyria cutanea tarda
B) Acute intermittent porphyria
C) Erythropoetic protoporphyria
D) X-linked sideroblastic anaemia

B

7

A porphyria with erythema, no blistering or bullae, is most likely:

A) Porphyria cutanea tarda
B) Acute intermittent porphyria
C) Erythropoetic protoporphyria
D) X-linked sideroblastic anaemia
E) CEP

C

8

TSH <0.01U/L
Free T3 15.6pmol/L
Free T4 38.0pmol/L

A) Clinical primary hypothyroidism
B) Euthyroid status in a patient complaining of tiredness
C) Pituitary driven thyrotoxicosis
D) Secondary or pituitary hypothyroidism
E) Subclinical hypothyroidism with risk of later clinical hypothyroidism
F) Thyrotoxicosis
G) To screen for medullary thyroid carcinoma
H) To screen for recurrence of differentiated thyroid carcinoma

F

9

TSH 8.4U/L
Free T4 11.7pmol/L
Thyroid peroxidase antibodies positive

A) Clinical primary hypothyroidism
B) Euthyroid status in a patient complaining of tiredness
C) Pituitary driven thyrotoxicosis
D) Secondary or pituitary hypothyroidism
E) Subclinical hypothyroidism with risk of later clinical hypothyroidism
F) Thyrotoxicosis
G) To screen for medullary thyroid carcinoma
H) To screen for recurrence of differentiated thyroid carcinoma

E

10

TSH 1.4U/L
Free T4 12.1pmol/L

A) Clinical primary hypothyroidism
B) Euthyroid status in a patient complaining of tiredness
C) Pituitary driven thyrotoxicosis
D) Secondary or pituitary hypothyroidism
E) Subclinical hypothyroidism with risk of later clinical hypothyroidism
F) Thyrotoxicosis
G) To screen for medullary thyroid carcinoma
H) To screen for recurrence of differentiated thyroid carcinoma

B

11

TSH 22.4U/L
Free T4 6.3pmol/L

A) Clinical primary hypothyroidism
B) Euthyroid status in a patient complaining of tiredness
C) Pituitary driven thyrotoxicosis
D) Secondary or pituitary hypothyroidism
E) Subclinical hypothyroidism with risk of later clinical hypothyroidism
F) Thyrotoxicosis
G) To screen for medullary thyroid carcinoma
H) To screen for recurrence of differentiated thyroid carcinoma

A

12

Thyroglobulin 254ug/L

A) Clinical primary hypothyroidism
B) Euthyroid status in a patient complaining of tiredness
C) Pituitary driven thyrotoxicosis
D) Secondary or pituitary hypothyroidism
E) Subclinical hypothyroidism with risk of later clinical hypothyroidism
F) Thyrotoxicosis
G) To screen for medullary thyroid carcinoma
H) To screen for recurrence of differentiated thyroid carcinoma

H

Medullary thyroid carcinoma would be screened for using calcitonin or CEA.

13

Which has the lowest calcium?

A) Primary hyperparathyroidism
B) Secondary hyperparathyroidism
C) Osteoporosis
D) Paget's disease of bone
E) Breast cancer

B

14

Newborn babies, in contrast to adults, have:

A) A higher haemoglobin
B) A lower white cell count
C) Smaller red blood cells
D) The same percentage of haemoglobin F

A

15

Newborn babies, in contrast to adults, have:

A) A higher haemoglobin
B) A lower white cell count
C) Smaller red blood cells
D) The same percentage of haemoglobin F

A

16

Newborn babies, in contrast to adults, have:

A) A higher haemoglobin
B) A lower white cell count
C) Smaller red blood cells
D) The same percentage of haemoglobin F
E) All of the above

A

17

Complications of sickle cell anaemia that are more common in adults than children include:

A) Hand-foot syndrome
B) Hyposplenism
C) Red cell aplasia
D) Splenic sequestration
E) Stroke
F) All of the above

B

18

Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count - likely diagnosis?

A) Splenic sequestration
B) Parvovirus B19 infection
C) Folic acid deficiency
D) Haemolytic crisis
E) Vitamin B12 deficiency

B

19

A 6-year-old Afro-Caribbean boy presents with chest and abdominal pain; Hb is 63g/DL, MCV 85fL, and blood film shows sickle cells. The most likely diagnosis is:

A) Sickle cell trait
B) Sickle cell anaemia
C) Sickle cell/beta thalassaemia

B

20

A 7-year-old Afro-Caribbean boy has abdominal pain and urinary tract symptoms and was given an anti-emetic by his GP. Three days later he had yellow eyes, and was brought to the hospital.

WCC 10.9x10^9/L
Hb 58g/L
MCV 100fL
Platelets 275x10^9/L

His blood film shows irregularly contracted cells and reticulocytes.

What is the likely diagnosis?

A) Hepatitis A
B) Hepatitis B
C) Hereditary spherocytosis
D) Sickle cell anaemia
E) G6PD deficiency

E

21

Complications of sickle cell anaemia that are more common in adults than children include:

A) Hand-foot syndrome
B) Hyposplenism
C) Red cell aplasia
D) Splenic sequestration
E) Stroke
F) All of the above

B

22

Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count - likely diagnosis?

A) Splenic sequestration
B) Parvovirus B19 infection
C) Folic acid deficiency
D) Haemolytic crisis
E) Vitamin B12 deficiency

B

23

A 6-year-old Afro-Caribbean boy presents with chest and abdominal pain; Hb is 63g/DL, MCV 85fL, and blood film shows sickle cells. The most likely diagnosis is:

A) Sickle cell trait
B) Sickle cell anaemia
C) Sickle cell/beta thalassaemia

B

24

A 7-year-old Afro-Caribbean boy has abdominal pain and urinary tract symptoms and was given an anti-emetic by his GP. Three days later he had yellow eyes, and was brought to the hospital.

WCC 10.9x10^9/L
Hb 58g/L
MCV 100fL
Platelets 275x10^9/L

His blood film shows irregularly contracted cells and reticulocytes.

What is the likely diagnosis?

A) Hepatitis A
B) Hepatitis B
C) Hereditary spherocytosis
D) Sickle cell anaemia
E) G6PD deficiency

E

25

A 1-year-old boy presents with joint bleeding. Hb, WCC, and platelets are normal. aPTT is prolonged, PT is prolonged, and bleeding time is normal. What’s the most likely diagnosis?

A) Haemophilia A
B) Haemophilia B
C) Von Willebrand disease
D) Thrombotic thrombocytopenic purpura
E) Has taken mother’s warfarin tablets

A

Haemophilia A is more likely than B.

TTP would show decreased platelets.

26

A 39-year-old female presents with recent onset jaundice and hepatomegaly. She was treated for breast cancer 4 years previously.

Hb 87g/L
Reticulocyte 15x10^9/L
Bilirubin (conjugated) 50umol/L

Her bloods are DAT negative, and her blood film shows nucleated red blood cells.

What is the most likely cause of her anaemia?

A) Iron deficiency anaemia
B) Anaemia of chronic disease
C) Bone marrow metastases from breast cancer
D) Microangiopathic haemolytic anaemia
E) Autoimmune haemolytic disease

C

27

A 45-year-old male presents with a 3-week history of sore throat. He has had a recent episode of shingles, and his EBV IgG serology is positive.

Lymphocytes: 12x10^9/L
Neutrophils: 7x10^9/L

His blood film shows reactive lymphocytes with no abnormal cells. Flow cytometry shows 82% kappa expressing B-cells with 0% lambda.

What is the likely diagnosis?

A) B cell acute lymphoblastic leukaemia
B) Mature B cell lymphoproliferative disorder
C) Infectious mononucleosis
D) T cell acute leukaemia lymphoma

B

Not acute because no abnormal cells found. Not glandular fever because would expect polyclonal B cells (combination of kappa and lambda chains). IgG positive just means he has had EBV in the past.

28

A 22-year-old female presents with drenching night sweats and a mediastinal mass. Biopsy shows Hodgkin’s lymphoma.

CT shows mediastinal and cervical node involvements.

What stage is she?

A) IA
B) IB
C) IIA
D) IIB
E) IIIA
F) IIIB
G) IVA
H) IVB

D

29

The risk of thrombosis is increased by:

A) Reduced prothrombin
B) Thrombocytopenia
C) Reduced protein C
D) Elevated antithrombin
E) Increased fibrinolysis

C

30

The highest risk of thrombosis is conferred by:

A) Factor V Leiden
B) Antithrombin deficiency
C) Family history of thrombosis
D) Reduced Factor VII level
E) 3-hour plane flight

B

31

How does warfarin achieve its antithrombotic effect?

A) Reduction in plasma proteins C and S
B) Blocks phospholipid synthesis
C) Reduction in plasma procoagulant factors
D) Acts as a cofactor for antithrombin
E) Inhibits factors II, VII, IX, and X

C

32

Which patient is most likely to benefit from long-term anticoagulation after developing a DVT?

A) A 57-year-old man after flying from Berlin
B) A 27-year-old woman during pregnancy
C) A 33-year-old woman on the combined oral contraceptive pill
D) A 77-year-old man after a hip replacement
E) A 30-year-old man after a long walk

E

Long-term anticoagulation is unlikely to benefit those in high risk situations (e.g. pregnancy, flying, post-surgery) as each of these situations is short term only, and the risk will decrease as the situation passes.

The man who developed a DVT after a long walk despite being so young has had an idiopathic thrombosis, and is more prone to have recurrent thrombosis.

33

A 53-year-old man presents with weight loss and abdominal discomfort. On examination, he has hepatosplenomegaly.

Hb 98g/L
WCC 20x10^9/L
Platelets 60x10^9/L

BCR/ABL transcripts were not detected. JAK2 V617F is positive. BM aspirate gave a dry tap, and a leucoerythroblastic picture.

What is the likely diagnosis?

A) CML chronic phase
B) Bone marrow metastases from prostate cancer
C) Primary myelofibrosis
D) CML blast crisis

C

34

A 22-year-old male with cyanotic congenital heart disease presents. He has no splenomegaly. His haemoglobin is 210g/L and haematocrit is 60%.

What are likely results of JAK2 V617F and serum erythropoietin?

A) JAK negative, EPO low
B) JAK positive, EPO high
C) JAK negative, EPO high
D) JAK positive, EPO low

C

35

A 35-year-old woman with CML presents on treatment with imatinib. Her blood results at diagnosis, 12m in, and now (24m) are shown.

Hb (g/L): 16 13 9
WCC (x10^9/L: 300 8.5 35
Platelets (x10^9/L): 800 320 24
%Blasts: 2 0 25
BCR-ABL: 100 0.01 10

What phase of disease is she currently in?

A) Chronic phase
B) Accelerated phase
C) Blast crisis

C

Blast % of over 20% is a diagnosis of acute leukaemia, so this is blast crisis.

36

Which of the following statements concerning myelodysplastic syndromes is true?

A) Myelodysplasia has a bimodal age distribution
B) The primary modality of treatment is intensive chemotherapy
C) 1/3 of patients can be expected to die from leukaemia transformation
D) There is no good correlation between severity of cytopenia and overall life expectancy
E) White cell function is frequently well-preserved

C

37

Which of the following statements concerning aplastic anaemia is true?

A) Immunosuppressive therapy is only used to treat a minority of patients with aplastic anaemia
B) If treated with immunosuppression, then relapse of aplastic anaemia occurs in less than 15% of cases
C) The cure rate of AA treated by sibling-related allogeneic stem cell transplantation in a patient under 40 years is >70%
D) Severe aplastic anaemia is differentiated from non-severe aplastic anaemia on the basis of the acquired cytogenetic abnormalities in the bone marrow
E) Leucodepletion of cellular blood products is only exceptionally undertaken for patients with aplastic anaemia

C

38

Which of the following is true?

A) Telomeric shortening is a feature of both idiopathic aplastic anaemia and dyskeratosis congenita
B) Development of malignancy is an uncommon complication of Fanconi's anaemia
C) A single genetic defect has been identified as the underlying cause of Fanconi's anaemia
D) Fanconi's anaemia is usually inherited in an autosomal dominant fashion
E) Telomeric function is considered to be unimportant in the pathophysiology of dyskeratosis congenita

A

39

During normal pregnancy...

A) Less iron is required
B) There is an increase in haemoglobin concentration
C) The platelet count falls
D) The neutrophil count falls

C

40

Coagulation changes in pregnancy...

A) Increase the likelihood of bleeding
B) Result in a hyperfibrinolytic state
C) Are mediated by BHCG hormone
D) Result in a leading cause of maternal mortality

D

The leading cause is VTE.

41

VTE during pregnancy...

A) Has a higher incidence than during postnatal period
B) Is more common in women with high BMI
C) Is more likely to occur following vaginal delivery than elective C Section
D) Usually affects right leg

B

42

Which of the following statements is correct?

A) In gestational thrombocytopenia the baby's platelet count is usually affected
B) Thrombocytopenia is rarely round in association with pre-eclampsia
C) Thrombotic thrombocytopenic purport remits spontaneously following delivery
D) The platelet count may fall following deliver in babies born to mothers with ITP

D

43

A reduction in pregnancy-associated thrombosis mortality rate can be attributed to...

A) Lower obesity rates
B) Improved targeted thromboprophylaxis
C) Rising maternal age
D) Increase in prevalence of gestational thrombocytopenia

B

44

Which of the following statements is correct?

A) Decision to use antithrombotic therapy in pregnant women with history of recurrent pregnancy loss should be based on results of thrombophilia testing
B) Aspirin and heparin have been shown to improve live birth rate in women with recurrent pregnancy loss and antiphospholipid antibodies

B

45

Which of the following statements is correct?

A) 1 litre blood loss can be considered normal following vaginal delivery
B) Uterine atony is a common cause of post partum haemorrhage
C) Post partum haemorrhage is often caused by the changes in coagulation factors in pregnancy

B

46

A blood film shows fragmented red blood cells and reticulocytes in pregnancy. Which is the most likely diagnosis?

A) Folate deficiency
B) Iron deficiency anaemia
C) HELLP syndrome
D) Sickle cell anaemia

C

47

A 22-year-old motorcyclist is involved in a road traffic accident, and is transfused two units of blood. Four hours later he develops acute shortness of breath and hypoxia, and despite attempts at ventilation deteriorates rapidly and foes into respiratory arrest. An autopsy shows evidence of massive pulmonary oedema with granulocyte aggregation within the pulmonary microvasculature. The most likely diagnosis is:

A) Anaphylaxis
B) ABO incompatible blood transfusion
C) Fluid overload
D) Transfusion related acute lung injury
E) Air embolism

D

TRALI is rare, but a leading cause of transfusion-related mortality. The classical presentation is non-cariogenic pulmonary oedema, possibly due to donor HLA antibodies aggregating patient WBCs in pulmonary capillaries. Treatment is supportive: stop the infusion, giving fluids, and ventilation if necessary.

Anaphylaxis is also an immediate reaction, but presents with rash, urticaria, and wheeze.

ABO mismatching is acute intravascular haemolysis, with restlessness, chest or loin pain, hypotension, fever, vomiting, flushing, collapse, and haemoglobinuria.

Fluid overload is common but unlikely with only 2 units of blood and this rapid an onset.

Air embolism is a rare complication of air bubbles in the blood bag, and presents with circulatory collapse.

48

A 43-year-old woman is transfused three units of blood as an emergency following prolonged haematemesis. A few minutes later she becomes restless, and complains of chest pain. On examination she is pyrexial and tachycardic with a BP of 95/60. There is bleeding at the site where her annular is inserted, and urinalysis reveals haemoglobinuria. The most likely diagnosis is:

A) Anaphylaxis
B) ABO incompatibility
C) Myocardial infarction
D) Graft versus host disease
E) Bacterial contamination

B

ABO mismatching is acute intravascular haemolysis, with restlessness, chest or loin pain, hypotension, fever, vomiting, flushing, collapse, and haemoglobinuria. Treatment by stopping the transfusion, fluid resuscitation, and inotropic support. ICU transferral is recommended. The blood bank should be urgently informed in case of a mistake in which bags have been swapped, so that another patient isn't also mismatched.

Anaphylaxis is also an immediate reaction, but presents with rash, urticaria, and wheeze.

MI would not cause intravascular haemolysis.

Graft versus host disease is a delayed reaction, and wouldn't be this acute.

Bacterial contamination would not cause pain or haemoglobinuria, but otherwise can present similarly.

49

An 83-year-old woman with myelodysplasia is found to have a haemoglobin of 6.2 on admission. She is transfused two units of blood, and is discharged 2 days later. Six days after her admission, her carer calls the GP with concerns that she is feverish and her skin looks slightly yellow. She is readmitted to hospital where blood tests reveal the following: bilirubin 35, ALT 15 (5-35), ALP 82 (20-140), Hb 7.3g/dL, platelets 264x10^9/L. The most likely diagnosis is:

A) Febrile haemolytic transfusion reaction
B) Hepatitis B
C) Graft versus host disease
D) Post-transfusion purpura
E) Delayed haemolytic transfusion reaction

E

Delayed haemolytic transfusion reactions occur >24h post-transfusion. They are a result of patient sensitisation against red cell antigens (commonly Kidd or Rh) from previous transfusions or pregnancies.

It causes falling haemoglobin concentration, fever, jaundice, haemoglobinuria, and renal failure. Treatment should monitor renal function, repeating group and screen, and notifying the blood bank.

Febrile haemolytic reactions are acute and due to patient antibodies reacting with donor white cell antigens, or a build-up of cytokines during storage. It requires slowing the transfusion, and giving an antipyretic if necessary.

Hepatitis B is rarer now as blood products are screened for the virus, along with hepatitis C, HIV, HTLV, and syphilis.

Graft vs host disease is a rare delayed reaction in immunosuppressed patients, causing liver failure, diarrhoea, skin rashes, and bone marrow failure.

Post-transfusion purpura is a rare delayed reaction 5-9d post) in which a severe thrombocytopenia and potentially lethal bleeding occurs. It is treated with IV immunoglobulin therapy.

50

An 8-year-old boy is brought to his GP by his father, who reports that he has been feeling progressively more tired over the past few months. On examination, the GP notices a slight yellowing of his sclera, and the presence of splenomegaly. His father recollects that he himself was told he had a problem with his blood cells as a child, but has never been affected by it. A peripheral blood film shows a raised reticulocyte count and spherocytes. He is likely to have a positive:

A) Coombs test
B) Osmotic fragility test
C) G6PD test
D) Sickle cell screen
E) Schilling test

B

Osmotic fragility test is for hereditary spherocytosis or elliptocytosis. Spherocytosis is a result of dysfunctional vertical defects in the red cell membrane such as ankyrin, band 4.2, or spectrin. The osmotic fragility test confirms spherocytes are present, but this could also be a result of any haemolytic anaemia, particularly autoimmune.

Coombs test is for autoimmune haemolytic anaemia, and is also known as the direct anti globulin test.

G6PD is an enzyme in RBCs. Deficiency causes a haemolytic anaemia in response to oxidative stress, with triggers such as broad beans, drugs, or exercise.

The sickle screen test looks for sickle cell anaemia.

The Schilling test is used for vitamin B12, to see if the haemolytic anaemia is pernicious.

51

A 33-year-old Turkish man presents with extreme tiredness and shortness of breath after being started on a course of anti-malarial tablets. A full blood count reveals an Hb of 6.8. His Coombs test is negative. The cell type most likely to be found on his blood film is:

A) Heinz bodies
B) Pencil cells
C) Target cells
D) Spherocytes
E) Sickle cells

A

G6PD is an enzyme in RBCs. Deficiency causes a haemolytic anaemia in response to oxidative stress, with triggers such as broad beans, drugs (anti-malarial, sulphonamides, vitamin K, dapsone), or exercise. It's X-linked recessive. Heinz bodies are characteristically seen on blood film during crises. They're RBC inclusions due to denatured haemoglobin.

Pencil cells are elliptocytes seen in iron deficiency anaemia, thalassaemia, and pyruvate kinase deficiency.

Target calls are seen in hepatic pathology, hyposplenism, and haemoglobinopathies.

Spherocytes are seen in autoimmune haemolytic anaemias, and hereditary spherocytosis.

Sickle cells are found in sickle cell anaemia.

52

A 25-year-old student is treated for infectious mononucleosis following a positive Paul Bunnell test. A blood film reveals target cells, Howell-Jolly bodies, and atypical lymphocytes. Together, these suggest that he has features of:

A) Bone marrow suppression
B) Hyposplenism
C) Disseminated intravascular coagulation
D) Haemolytic anaemia
E) Liver failure

B

Hyposplenism can be a result of splenectomy, sickle cell anaemia, coeliac disease, ulcerative colitis, or trauma. Splenectomies are indicated in massive splenomegaly, thalassaemia, pyruvate kinase deficiency, immune haemolytic anaemia, idiopathic thrombocytopenia purpura, elliptocytosis, and hereditary spherocytosis. Post-splenectomy, patients require life-long penicillin, and vaccines for pneumococcus, Hib, and meningococcus. Blood films show Howell-Jolly bodies, target cells, occasional nucleated RBCs, lymphoctosis, macrocytosis, and acanthocytes.

This patient's atypical lymphocytes are a result of his infectious mononucleosis.

53

A 4-year-old Afro-Caribbean boy has chest and abdominal pain. His blood tests reveal an Hb of 6.1g/dL, with an MCV of 65. A blood film shows the presence of sickle cells. The most likely diagnosis is:

A) Sickle cell trait
B) Sickle cell anaemia
C) Sickle cell/B-thalassaemia
D) Sickle cell/haemoglobin C
E) B-thalassaemia

B

Sickle cell disease encompasses sickle cell anaemia, sickle cell/B thalassaemia, and sickle cell/haemoglobin C. The latter two are less likely in this vignette.

Sickle cell trait is asymptomatic, though does confer some resistance against malaria.

54

A 7-year-old child has known sickle cell disease. He presents with a 5-day history of fever, shortness of breath, and extreme fatigue. His mother reports that his younger brother, who also has sickle cell disease, has been feeling unwell too, recently. A blood test for the patient reveals a severe anaemia and low reticulocyte count. He has most likely developed:

A) Splenic sequestration
B) Pneumococcal infection
C) Vaso-occlusive crisis
D) Folic acid deficiency
E) Parvovirus B19 infection

E

Aplastic crisis can be a result of many triggers. In this case, the fever and the sibling point to an infectious cause.

Parvovirus B19 invades erythrocyte precursors and destroys them. Normally, this is self-limiting and improves after 2-3d with no symptoms. However, if RBC life span is limited (as in sickle cell)), it can be a life-threatening virus.

Splenic sequestration is potentially fatal. RBCs sequester in the enlarged spleen of younger patients, causing circulatory failure. Recurrent infarcts in older children causes hyposplenism, so this becomes less likely with age.

Pneumococcal infection is high-risk in hyposplenism, but wouldn't cause low reticulocyte count.

Vaso-occlusive crises are a result of sickle cell adhesion and occlusion. Significant pain, anaemia, and reticulocytopenia would occur.

Folic acid deficiencies are more common in sickle cell, and can cause aplastic crises, but is less likely than an infectious cause.

55

A 26-year-old pregnant woman is found to have a Hb of 9.5g/dL on a routine blood test, with an MCV of 70. Serum electrophoresis reveals an Hb A2 of 3.9% and HbA of 96.1%. Her ferritin levels are normal. The most likely diagnosis is:

A) Iron deficiency anaemia
B) Cooley's anaemia
C) B-thalassaemia intermedia
D) B-thalassaemia minor
E) a-thalassaemia

D

The haemoglobin molecule is made up of four subunits. a2b2 is HbA, a2d2 is HbA2 (usually 1.5-3.5%), and a2y2 is HbF. B-thalassaemia minor is when one of the B alleles is mutated, causing a mild, asymptomatic, microcytic anaemia (Hb>9). HbA2 will increase (3.5-4%) to compensate.

B-thalassaemia major, or Cooley's anaemia, is homozygous absence of B alleles on chromosome 11. Patients present with severe anaemia and failure to thrive in the 1st year of life. Extramedullary haematopoeisis can cause skull bossing and hepatosplenomegaly. Life-long blood transfusions and iron chelation is indicated, as is splenectomy if hypersplenism continues. Bone marrow transplant can offer the chance of a cure.

B-thalassaemia intermedia falls in between the two states, not requiring blood transfusions.

a-thalassaemia is caused by mutations in the 2 alleles on each chromosome 16. One mutation is clinically normal. Two cause asymptomatic low MCV. Three causes HbH, causing haemolytic anaemia of moderate severity. Four deletions is Bart's hydros, and causes death in utero.

56

A 24-year-old unemployed man presents to his GP with a 4-week history of flu-like symptoms and a persistent dry cough. On examination, he has a maculopapular rash. A blood film reveals a haemolytic anaemia, and he is positive for cold agglutinins. The most likely organism implicated is:

A) Streptococcus pneumoniae
B) Mycoplasma pneumoniae
C) Legionella pneumphilia
D) Chlamydophila psittacosis
E) Borrelia burgdorferi

B

Autoimmune haemolytic anaemia (AIHA) can be cold or warm, depending on the optimal temperature of antibody binding to RBCs. Cold AIHA is mediated by IgM, and is aggravated in cold conditions, causing Raynaud's or acrocyanosis in severe cases. Most cases are idiopathic, but can also be caused by lymphoproliferative disease, and infections such as mycoplasma, or EBV.

Warm AIHA is IgG mediated, and leads to spherocytosis. It can be caused by lymphoproliferative disease, penicillin, and SLE.

57

A 7-year-old boy is taken ill from school on a cold December day, with a presumed viral infection. On returning home that day, he begins to feel even more unwell with a very high fever, headache, and abdominal pain. His father begins to worry that his skin has taken on a yellow tinge, and the boy says his urine is a dark-reddy brown colour. He is taken to the GP, and after several tests the presence of Donath-Landsteiner antibodies is reported. This child is suffering from:

A) Paroxysmal cold haemoglobinuria
B) Paroxysmal nocturnal haemoglobinuria
C) Sickle cell disease
D) Acute intermittent porphyria
E) Epstein-Barr virus

A

PCH affects children acutely after infection, with haemoglobinuria and jaundice after cold exposure. Donath-Landsteiner antibodies bind to RBCs and induce intravascular haemolysis in the cold. It is usually transient and self-limiting.

PNH is potentially life-threatening. It causes pancytopenia, thrombophilia, and intravascular haemolytic anaemia. Flow cytometry is the diagnostic test, replacing Ham's test.

Sickle cell crises can be caused by cold, but pain would be the main complaint.

AIP is an autosomal dominant condition causing neurovisceral symptoms, with characteristic deep red coloured urine.

EBV alone cannot cause these symptoms, but can trigger PCH.

58

A 21-year-old student has recently been diagnosed with coeliac disease. She presents to her GP complained of increased tiredness and shortness of breath on climbing stairs. Which of the following are most likely to be raised in this patient?

A) Serum iron
B) Haematocrit
C) Transferrin
D) Ferritin
E) Mean cell haemoglobin

C

IDA presents with low Hb, low MCV, and low MCH. Blood film shows hypo chromic RBCs with anisocytosis and poikilocytosis (variations in size and shape respectively). Serum iron would be low, and ferritin (the intracellular iron store) would be low. However, note that ferritin is an acute phase protein. Haematocrit is the percentage of RBCs in the blood, and may be low in anaemia.

Transferrin is a glycoprotein that binds to iron. In IDA, the liver secretes more to compensate.

59

A 34-year-old woman with known Addison's disease is brought to the GP by her husband, as he is concerned that she keeps falling over at night. On examination, the GP notices that she has conjunctival pallor. A thorough neurological examination reveals absent knee jerks, absent ankle jerks, and extensor plantars bilaterally. What of the following is the most sensitive test for the condition she has developed?

A) Anti-intrinsic factor antibodies
B) Anti-endomysial cell antibodies
C) Anti-smooth muscle antibodies
D) Anti-parietal cell antibodies
E) Anti-voltage gated calcium channel antibodies

D

This woman has subacute degeneration of the cord (SACD) causing symmetrical dorsal column loss and corticospinal tract loss. The neurological findings in this case are the classical triad in this condition. The falling may also be caused by optic atrophy (also caused by B12 deficiency).

Pernicious anaemia is associated with autoimmune conditions such as Addison's and thyroid disease. Autoimmune atrophic gastritis is the cause, with attack on parietal cells and intrinsic factor. Intrinsic factor antibodies are found in 50% of cases, and anti-parietal cell antibodies are found in >90%.

Anti-endomysial cell antibodies are found in coeliac disease.

Anti-smooth muscle antibodies are found in autoimmune hepatitis and primary biliary cirrhosis.

Anti-VGCC antibodies are found in Labert-Eaton syndrome (a variation of myasthenia gravis).

60

A 58-year-old woman is referred to a haematology clinic following repeated chest infections and epistaxis. On examination, the doctor notes that she has conjunctival pallor and some petechial rashes on her forearms, but no organomegaly. her blood tests reveal a pancytopenia, and an MCV of 112. Her drug history includes omeprazole, carbamazepine, gliclazide, metformin, paracetamol, and simvastatin. A bone marrow biopsy reveals a hypo cellular marrow. The most likely diagnosis is:

A) Aplastic anaemia
B) Myelodysplasia
C) Hypothyroidism
D) Chronic myeloid leukaemia
E) Myeloma

A

61

A 50-year-old diabetic man sees his GP complaining of generalised tiredness and a painful right knee. He is found on examination to have five finger breadths of hepatomegaly. An X-ray of his right knee is reported as showing chondrocalcinosis. His blood tests are likely to reveal:

A) Raised MCV
B) Raised total iron binding capacity
C) Reduced serum ferritin
D) Reduced iron level
E) Raised transferrin saturation

E

62

A 64-year-old woman is seen in the haematology clinic with generalised bone pain and recurrent infections. Following a set of blood tests, a skeletal survey reveals multiple lytic lesions and a bone marrow biopsy reports the presence of >10% plasma cells. Her blood tests are most likely to have shown:

A) Raised calcium, normal ALP, raised ESR
B) Normal calcium, raised ALP, normal ESR
C) Raised calcium, raised ALP, raised ESR
D) Raised calcium, normal alkaline phosphatase, raised CRP
E) Normal calcium, normal ALP, raised CRP

A

This woman has multiple myeloma. ALP is often normal (unlike other bone malignancies). High plasma protein concentrations cause rouleaux formation and high ESR.

Symptomatic myeloma: >10% clonal cells, serum or urine paraprotein, evidence of end-organ damage (CRAB: Calcium, Renal, Anaemia, Bone)

Asymptomatic (smouldering) myeloma: >10% clonal cells and/or serum paraprotein >30/L with no CRABs

MGUS: <10% clonal cells, <30g/L serum paraprotein, no CRABs

63

A 67-year-old woman presented with polyuria and polydipsia on a background of ongoing bone pain. Her blood tests revealed a high calcium, and a serum electrophoresis was sent. Her serum paraprotein was 25g/L, and a bone marrow biopsy revealed 6% clonal plasma cells. The most likely diagnosis is:

A) Plasma cell dyscrasia
B) Monoclonal gammopathy of undetermined significance
C) Smouldering myeloma
D) Multiple myeloma
E) Hypercalcaemia with no evidence of underlying malignancy

D

Symptomatic myeloma: >10% clonal cells, serum or urine paraprotein, evidence of end-organ damage (CRAB: Calcium, Renal, Anaemia, Bone)

Asymptomatic (smouldering) myeloma: >10% clonal cells and/or serum paraprotein >30/L with no CRABs

MGUS: <10% clonal cells, <30g/L serum paraprotein, no CRABs

Plasma cell dyscrasia is a general term describing cancers of plasma cells, including myeloma, MGUS, solitary plasmacytoma of bone, and Waldenstrom's macroglobulinaemia.

64

A 39-year-old motorcyclist is admitted following a road traffic accident complicated by severe burns. Several days later, he is due to go home when oozing is noticed from his cannula site, and he has several nose bleeds. Repeat bloods reveal an Hb of 12.2g/dL, WCC of 11.2x10^9/L, and platelets of 28x10^9L. A coagulation screen shows prolonged APTT and PT. He also has a reduced fibrinogen and raised D-dimers. The most likely diagnosis it:

A) Liver failure
B) Disseminated intravascular coagulation
C) Thrombotic thrombocytopenia purpura
D) Aplastic anaemia
E) Heparin induced thrombocytopenia

B

65

A 46-year-old woman is brought to accident and emergency by her daughter who reports that she had been feeling unwell for a few days with a fever, and is now hallucinating. On examination, she has a temperature of 38.9 degrees Celsius. She's noted to be pale, and has widespread purpura over both arms. Blood tests reveal an Hb 9.1g/dL, platelet count of 60x10^9/L, creatinine of 226 and urea 16.7. A blood film is reported as showing the presence of schistocytes. The most likely diagnosis is:

A) Weil's disease
B) Glandular fever
C) Idiopathic thrombocytopenia purpura
D) Thrombotic thrombocytopenia purpura
E) Haemolytic uraemic syndrome

D

TTP consists of a MAHA with fever, renal failure, CNS symptoms, and low platelets. It is caused by inhibition of a protease by antibodies (e.g. autoimmune, bacterial infection) leading to large vWF multimers which cause platelet aggregation and fibrin deposition in small vessels. Urgent plasma exchange is required, as this is potentially fatal (>95% if untreated).

Weil's disease is caused by a spirochaete spread in rat urine. It can cause renal failure and fever, but not MAHA.

Glandular fever can cause palatal petechiae, but CNS signs, purpura, thrombocytopenia, and anaemia are unlikely.

ITP is an autoimmune disorder caused by IgG against platelets. It's treated with steroids, anti-D, immunosuppression, and splenectomy, dependent on severity.

HUS is a MAHA caused by verotoxin from E. coli 0157. It attacks endothelial cells and causes anaemia, thrombocytopenia, renal failure, and schistocyte production. It is unlikely to affect adults, though, and CNS signs are also unlikely. A preceding GI illness would be expected.

66

A 28-year-old woman in her 29th week of pregnancy comes to accident and emergency with epigastric pain, nausea, and vomiting. She also complains that her hands and feet have been swelling up. On examination, her blood pressure is 165/96, HR 125bpm, and she is pyrexial. She is noted to have yellowing of the sclera and right upper quadrant tenderness. Blood tests reveal an Hb of 10.1, platelets 96, WCC 11.3, LDH 820 (70-250), AST 115 (5-35), and ALT 102 (5-35). Her coagulation screen is normal and a blood film is reported as showing the presence of schistocytes. The most likely diagnosis is:

A) Hepatitis
B) Thrombotic thrombocytopenia purpura
C) Pre-eclampsia
D) Acute fatty liver of pregnancy
E) HELLP syndrome

E

67

A 56-year-old woman with known cirrhosis presents with falls. On examination, she is clinically jaundiced and rectal examination reveals malaena. Blood tests reveal and INR of 2.2. She is diagnosed with decompensated chronic liver disease. Which of the following is not a vitamin K dependent clotting factor?

A) Thrombin
B) Factor VII
C) Factor VIII
D) Protein C
E) Factor X

C

Vitamin K is used to synthesis factors II, VII, IX, and X, and proteins C, S, and Z. Vitamin K deficiencies or inhibition affects mainly the extrinsic pathway, as shown by an increased INR.

Factor VIII is synthesised by endothelial and sinusoidal cells in the liver.

68

A 46-year-old man presents with pain and swelling in the right calf 2 weeks after being fitted with a plaster cast to his leg after a fall. The calf is tender, erythematous and swollen. He is also a heavy smoker and slightly overweight. His admitting physician suspects a deep vein thrombosis (DVT) and books an ultrasound of the calf. A DVT is confirmed, and 5mg warfarin is started the next day. Two days later, the same patient develops pain and swelling in other calf, an ultrasound confirms a further DVT in the contralateral leg. What factor is least likely to contribute to the development of the second DVT?

A) Smoking
B) Warfarin
C) Previous DVT
D) Being slightly overweight
E) Plaster cast

D

All factors may contribute, but being slightly overweight gives the lowest risk. Thrombosis risk factors can be categorised using Virchow's triad:

Vessel wall (injury, HTN)

Blood flow (immobility, venous stasis, varicose veins)

Blood content (hyperviscosity, hypercoagulability, cancer, smoking (increased TXA2 production), pregnancy, race, age, OCP)

Warfarin can induce a paradoxical hypercoagulable state as it inhibits vitamin K metabolism, and thus decreases the vitamin K dependent factors (factors II, VII, IX, and X, and proteins C, S, and Z). Protein C and S have shorter half-lives than the coagulation factors, so a transient hypercoagulable state can occur because of lack of inhibition. Usually, a LMWH should be given with warfarin until the INR stabilises.

69

A 54-year-old man presents with haematemesis. He has known varies and is currently vomiting large amounts of bright red blood. The admitting doctor takes some blood for fast analysis and confirms a haemoglobin of 4g/dL. The patient's haematemesis continues and he is transfused a total of 20 units of blood and 8 units of fresh frozen plasma in the next 24 hours. The patient underwent gastroscopy which revealed bleeding oesophageal varies which were successfully treated by endoscopic banding. His post-transfusion bloods are he following:
Hb 9.2g/dL
WCC 8.0x10^9/L
Platelets 57x10^9/L
Fibrinogen >1.0g/L
Prothrombin times and activated partial thromboplastin times are normal.

What is the most likely cause of his thrombocytopenia?

A) Disseminated intravascular coagulopathy
B) Alcohol excess
C) Massive blood transfusion
D) Megaloblastic anaemia
E) Hypersplenism

C

This patient underwent massive haemorrhage (100% circulating volume lost in 24h, or >50% circulating volume lost in 3h). His blood transfusion was of FFP and packed RBCs, but no platelet replacement. After massive transfusion, platelets should be kept above 50x10^9, but individual variation may require keeping levels above 75x10^9.

70

Which of the following is not often associated with a very high (>100mm/hour) erythrocyte sedimentation rate (ESR)?

A) Myeloma
B) Anaemia
C) Leukaemia
D) Aortic aneurysm
E) Malignant prostatic cancer

B

ESR is calculated by adding anticoagulant to a blood sample and waiting for RBCs to accumulate and sediment at the bottom of a test tube. Increased ESR can also cause Rouleaux formation on blood film.

ESR is increased by high levels of proteins that decrease the ionic repulsion between RBCs, including:

Fibrinogen (prostatic cancer)
Acute phase proteins (inflammation)
Immunoglobulins (inflammation, myeloma, leukaemia, aneurysm)

Sometimes, severe anaemia can falsely increase the ESR as the number of RBCs greatly decreases the ionic repulsion in between, but this rarely increases it to levels over 100mm/h.

71

A 62-year-old man presents with shortness of breath. This has been gradually getting worse for the last few years, and is associated with chronic productive cough. He is a heavy smoker. His chest x-ray shows a hyper expanded chest with no other abnormalities. His blood tests are normal except for a raised haemoglobin and raised haematocrit. What is the most likely cause for this?

A) Polycythaemia rubra vera
B) Idiopathic erythrocytosis
C) Secondary polycythaemia
D) Gaisbock's disease
E) Combined polycythaemia

E

Combined polycythaemia is also known as smoker's polycythaemia, and has 3 main aetiological factors.

1) CO from cigarettes bind to Hb and displace oxygen, causing an increase in erythropoeitin (EPO).

2) COPD obstructs airways and causes hypoxia, leading to EPO production

3) Smoking is associated with reduced plasma volume, leading to an increase in relative Hb concentration

Polycythaemia rubra vera is a chronic myeloproliferative disorder characterised by V617F mutation in JAK2. It causes raised red cell mass.

Idiopathic erythrocytosis is similar, caused by a JAK2 mutation but not V617F.

Secondary polycythaemia is a secondary increase in RBCs due to, for example, living at high altitudes (appropriate increase in EPO) or post-transplant erythrocytosis (inappropriate increase in erythropoetic hormones).

Relative or apparent polycythaemia is historically known as Gaisbock's disease, and is seen when there is a decrease in plasma volume but no change in red cells.

72

A 25-year-old black man develops jaundice and dark red urine 2 days after starting primaquine, an anti-malarial. His blood tests reveal a microcytic anaemia with raised bilirubin and urine dipstick is positive for blood. A peripheral blood film reveals 'bite cells' and Heinz bodies. The most likely diagnosis is:

A) Hereditary spherocytosis
B) Glucose-6-phosphate dehydrogenase deficiency
C) Paroxysmal nocturnal haemoglobinuria
D) Microangiopathic haemolytic anaemia
E) Autoimmune haemolytic anaemia

B

73

What are the likely laboratory findings for a patient with renal cell carcinoma with secondary polycythaemia who is not dehydrated?

A) Normal red cell count, normal red cell mass, increased erythropoietin concentration
B) Increased red cell count, increased red cell mass, increased erythropoietin concentration
C) Decreased red cell count, decreased red cell mass, normal erythropoietin concentration
D) Increased red cell count, decreased red cell mass, increased erythropoietin concentration
E) Decreased red cell count, increased red cell mass, decreased erythropoietin concentration

B

74

von Willebrand's disease is characterised by abnormal platelet aggregation when they are exposed to:

A) Streptomycin
B) Aspirin
C) Fibrinogen
D) Collagen
E) Ristocetin

E

75

An 18-month-old child with Down's syndrome presents with recurrent infections and petechial bleeding. A blood film was analysed, showing a particular distinctive feature of haematological malignancy. What is the most likely diagnostically helpful finding seen in this patient?

A) Smudge cell
B) Reed Sternberg cell
C) Auer rod
D) Pelger Huet anomaly
E) Hairy cell

C

76

An 8-year-old African boy presents with a large jaw mass which has been growing rapidly over the last few weeks. A histological sample was taken and a classical 'starry sky' appearance was observed. The most likely diagnosis is:

A) Follicular lymphoma
B) Marginal zone lymphoma
C) Burkitt's lymphoma
D) Diffuse large B cell lymphoma
E) Mantle cell lymphoma

C

77

A 35-year-old African-American man presents with painless lymphadenopathy, which he noted after shaving. He denies any recent infections, fevers, weight loss, or night sweats. A biopsy is performed which shows lymphocytic and histiolytic cells. A haematologist calls to confirm the diagnosis of non-classical Hodgkin's lymphoma. Which subtype is this?

A) Nodular sclerosis
B) Mixed cellularity
C) Nodular lymphocytic
D) Lymphocytic rich
E) Lymphocytic depleted

C

Non-classical Hodgkin's lymphoma is also known as nodular lymphocytic predominant lymphoma. It is characterised by lymphocytic and histiolytic (L&H) cells. These are also known as popcorn cells.

The other four types are classical Hodgkin's lymphoma subtypes, with nodular sclerosing being the most common (80%), followed by mixed cellularity (17%).

78

A 17-year-old boy with glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with tiredness and is noticed to be jaundiced. These features have developed since he was diagnosed with a chest infection 1 week ago. What is the most likely haematological finding?

A) Positive direct antiglobulin test
B) Low mean cell volume
C) Reduced reticulocyte count
D) Haemoglobinuria
E) Increased haptoglobin concentration

D

G6PD deficiency causes haemolytic anaemia when exposed to certain triggers causing oxidative stress on RBCs. Therefore, signs of intravascular haemolysis will present, including haemoglobinuria.

DAT is for autoimmune haemolytic anaemia.

Low MCV is seen when there is reduced haemoglobin content, for example in IDA, and anaemia of chronic disease. In haemolysis, MCV tends to increase as a result of more reticulocytes. Reduced reticulocytes are a sign of aplastic anaemia.

Haptoglobin circulates in plasma and binds to free haemoglobin to facilitate removal by the reticuloendothelial system. Therefore, it is reduced in intravascular haemolysis as more is bound.

79

A 35-year-old Asian woman presents with tiredness. The full blood count shows:

Hb 10.1g/dL (11.5-16.5)
Platelets 160x10^9/L (150-400x10^9)
WCC 6.6x10^9/L (4-11x10^9)
MCV 62fL (80-96)
HbA2 6.3% (2-3)

Which of the following is the most likely?

A) Sickle cell anaemia
B) Acute myeloid leukaemia
C) B-thalassaemia major
D) B-thalassaemia trait
E) Hereditary spherocytosis

D

This woman has a microcytic anaemia with an increased proportion of HbA2.

Thalassaemia is a reduction of absence of a globin gene. Hb is made up of two alpha and two beta chains. Beta chains come from one beta gene on chromosome 11.

The B(0) gene refers to absence of beta production, causing B-thalassaemia major. It presents in the first year of life with profound life-long transfusion dependent anaemia.

B(+) gene is known as B-thalassaemia trait or minor. It is usually asymptomatic, and causes patients to produce a reduced quantity or quality of B chains. It is compensated for by increasing production of HbA2 (made up of two alpha and two delta chains).

B-thalassaemia intermedia is a combination of 2 heterozygotic thalassaemia variants, for example B(+) with HbE.

80

A 62-year-old man presents with bruising and tiredness. Examination reveals moderate splenomegaly. His bloods show a normocytic anaemia, platelet count of 900x10^9, neutrophilia, basophilia, numerous myelocytes, and 4% myeloblasts. The neutrophils have low leukocyte alkaline phosphatase levels. Which of the following is likely to be present in this patient?

A) t(9;22)
B) t(8;14)
C) BCR-Abl fusion gene only
D) V617F point mutation in JAK2
E) 5q-syndrome

A

This is chronic myeloid leukaemia (increased myeloid cells). Leukocyte alkaline phosphatase is characteristically low in CML. The 9;22 translocation causes production of the BCR-Abl fusion gene, a tyrosine kinase required for transformation into CML. BCR-Abl can occur alone, but is uncommon, and more likely to be alongside many other leukaemogenic pathways.

t(8;14) is common in Burkitt's lymphoma, causing over expression of cmyc, an oncogene.

V617F mutations are found in 99% of cases of polycythaemia rubra vera.

5q- is a subtype of myelodysplastic syndrome.

81

Which of the following patients with Hodgkin's lymphoma has the worst prognosis?

A) 25-year-old man with inguinal lymphadenopathy
B) 25-year-old woman with mediastinal and inguinal lymphadenopathy
C) 25-year-old woman with mediastinal and inguinal lymphadenopathy and night sweats
D) 25-year-old woman with mediastinal and inguinal lymphadenopathy with 5% weight loss in last 6 months
E) 25-year-old man with cervical and mediastinal lymphadenopathy

C

The Ann Arbor staging system is as follows:

I - single nodal area involvement
II - 2+ nodal areas same side of diaphragm
III - 2+ nodal areas different sides of diaphragm
IV - extranodal or bone marrow involvement
Suffix A or B for absence or presence of B-symptoms respectively.

B symptoms include significant unexplained fever, night sweats, or weight loss of over 10% during 6m prior to diagnosis.

Therefore, patient C is a later stage, at IIIb.

82

A patient presents with acute promyelocytic leukaemia. What is the most likely mechanism of underlying leukaemogenesis?

A) Telomere shortening
B) Aberrant fusion of two genes
C) Impaired protein degradation
D) Over-expression of cellular oncogene
E) Post-translational modification

B

Acute promyelocytic leukaemia is a result of t(15;17), leading to production of the PML-RARA fusion gene. APML is associated with DIC, which should be noted in its treatment.

Leukaemias tend to be a result of fusion genes, chromosomal duplications leading to dosage effects (e.g. Down's syndrome), or chromosomal loss or deletion. A type I mutation promotes proliferation, and type II blocks differentiation and apoptosis. Both are generally present in acute leukaemia.

Telomere shortening is a normal outcome of ageing, but is noted in acquired and congenital aplastic anaemias (the latter in the form of dyskeratosiscongenita).

83

A 64-year-old man presents with lethargy, weight loss, and abdominal fullness. He is found to have chronic myeloid leukaemia. He is started on imatinib as part of the initial treatment to control his disease. What is the mechanism of action of imatinib?

A) Proteasome inhibitor
B) Tyrosine kinase inhibitor
C) IL-6 inhibitor
D) p53 inhibitor
E) Human epidermal growth factor receptor 2 protein inhibitor

B

84

A 16-year-old girl with mild von Willebrand's disease is scheduled for a dental extraction. She has had one previously where she required two units of blood transfused. What is the most appropriate treatment for this patient prior to surgery?

A) Cryoprecipitate
B) Desmopressin
C) Fresh frozen plasma
D) Vitamin K
E) Recombinant factor VIII concentrate

B

vWD has three types. Type I is a quantitive defect. Type II is a qualitative defect. Type III causes a profound deficiency.

Desmopressin acts to increase vWF and factor VIII concentration by encouraging release from endothelial cell storage sites. It's efficacious in types I and II. As this patient has a mild disease, desmopressin will likely be viable. Type III might require replacement or recombinant vWF.

Fresh frozen plasma is prepared from whole blood or plasma. It contains coagulation factors and proteins. It's useful for correcting clotting issues quickly, as in warfarin overdose, liver disease, and DIC.

Cryoprecipitate is fresh frozen plasma thawed at 4 degrees Celsius. The remaining precipitate is centrifuged and leaves high concentration factor VIII, fibrinogen, fibronectin, factor XIII,and vWF.

Vitamin K reverses warfarin overdose. It is the basis of synthesis of factors II, VII, IX, and X, and proteins C, S, and Z.

Recombinant factor VIII is used in life-threatening haemophilia type A.

85

An 80-year-old man presents with tiredness and lethargy. After initial work-up, a diagnosis of myelodysplastic syndrome is suspected. Which of the following is true about this condition?

A) A blood film will typically show neutrophil toxic granulation
B) If there are 1% blasts of the total white cell count, this represents leukaemia transformation
C) Cytotoxic chemotherapy is first line treatment
D) Mortality is more likely to be from infection than leukaemia transformation
E) Absence of the short arm of chromosome 5 is a subtype

D

Though MDS generally have a rule of thirds (1/3 infection, 1/3 bleeding, 1/3 transformation), it is weighted more away from transformations and towards infection.

Toxic granulation refers to dark blue, coarse granules seen in inflammatory or septic conditions. In MDS, Dohle bodies (light blue rER) and Pelger-Huet abnormalities (reduced nuclear lobule number) are more likely to be seen.

Leukaemia transformation requires >20% blasts. 5-19% is refractory anaemia with excess blasts, and lower than 5% is normal.

Cytotoxic chemotherapy is rarely first-line, only if they are symptomatic or high risk, and able to withstand the therapy. Treatment is usually supportive (blood products, antibiotics, growth factors).

A subtype of MDS is 5q-. This is deletion of the long arm, not the short (petit) arm.

86

A middle-aged woman comes to the dermatology clinic with a suspicious mole on her back. You decide excision is required, and during the history she says 'I have Factor V Leiden'. Which of the following best describes the pathophysiology of Factor V Leiden?

A) Prothrombin mutation
B) Activated protein C resistance
C) Antithrombin III deficiency
D) Protein C deficiency
E) Protein S deficiency

B

Protein C is responsible for inactivating factor Va by cleavage. Factor V Leiden confers resistance to this inactivation.

87

A 67-year-old woman presents to accident and emergency after having a fall. She is diagnosed with a fractured neck of femur which is fixed with a hemiarthroplasty. She also suffers from metastatic breast cancer. Four days postoperatively, she develops shortness of breath with an increased respiratory rate of 24/min. The doctor on call takes an arterial blood gas sample, which shows the following:

pH 7.48
O2 15.4kPa on 2L oxygen
CO2 2.6kPa
BE +1
Sats 99%

What does the blood gas show?

A) Metabolic alkalosis with respiratory compensation
B) Metabolic alkalosis
C) Respiratory alkalosis with metabolic compensation
D) Respiratory alkalosis
E) None of the above

D

88

A 19-year-old female student presents to the GP with low mood, lethargy, and muscle weakness. She is anxious that she is putting on weight and admits to purging after meals to keep her weight under control for several months. She has a past history of depression and is taking citalopram. On examination, her BMI is 18, she is clinically dehydrated with signs of anaemia, including conjunctival pallor. She has bilateral parotidomegaly and the GP also notices erosions of the incisors. He orders some blood tests:

Hb 9.5
WCC 7.8
Platelets 345
Na 143
K 3.1
Urea 8.5
Creatinine 64
Arterial pH 7.49

Urinalysis is normal except for acidic urine. The cause of this patient's acidic urine is:

A) Acute renal failure
B) Renal tubular acidosis
C) Citalopram
D) Anaemia
E) Physiological

E

This patient suffers from bulimia nervosa. Therefore, her alkalosis is likely due to excessive purging, removing H+ ions.

H+ ions are usually transported across cell membranes alongside K+. Therefore, low plasma H+

In the kidney, H+ and K+ are exchanged in the distal convoluted tubule. To compensate for the hypokalaemia, H+ is excreted, causing a paradoxical aciduria.

Acute renal failure would cause a hyperkalaemia, as K+ is actively secreted by the kidney, and metabolic acidosis due to a lack of bicarbonate.

Renal tubular acidosis is a lack of ability to acidify urine and hyperkalaemia.

Citalopram is an SSRI. SSRIs may cause hyponatraemia, but no hypokalaemia.

Anaemia doesn't usually cause electrolyte abnormalities.

89

A 55-year-old man with severe learning difficulties presents with shortness of breath on exertion, fever, and a productive cough rusty red sputum. On examination, there is increased bronchial breathing in the lower right zone with inspiratory crackles. The patient is clinically euvolaemic, and urine dipstick is normal. A CXR demonstrates right lower zone consolidation with the presence of air bronchograms. He is on carbemazepine for epilepsy and risperidone. Blood tests reveal:

Hb 13.4
WCC 12.8
CRP 23
Na 123
K 4.7
Urea 6
Creatinine 62

What is the most likely cause of hyponatraemia?

A) Pneumonia
B) Carbamezepine
C) Risperidone
D) Syndrome of inappropriate antidiuretic hormone (SIADH)
E) Cerebral salt wasting syndrome

B

Carbemazepine is well-characterised as being a cause of hyponatraemia, as well as being one of the three C's that cause aplastic anaemia (with carbimazole and chloramphenicol).

Pneumonia does not commonly cause hyponatraemia. Legionella pneumophila can rarely cause extrapulmonary symptoms including hyponatraemia, deranged LFTs, and lymphopenia.

90

A patient with end-stage renal failure presents with depression. He is on haemodialysis three times a week but feels it is not working anymore and is getting more tired lately. He says he has lost his appetite and consequently feels rather constipated too. He feels his mind is deteriorating and there is little worth in attending dialysis anymore. His doctor wants to exclude a reversible cause of his depression and orders some blood tests. The doctor finds the patient has a raised corrected calcium, normal phosphate levels, and high parathyroid hormone levels. What is the diagnosis?

A) Primary hyperparathyroidism
B) Secondary hyperparathyroidism
C) Tertiary hyperparathyroidism
D) Pseudohypoparathyroidism
E) Pseudopseudohypoparathroidism

C

PTH has 4 effects. It raises blood calcium by causing renal resorption, stimulates bone resorption of calcium, and increases the conversion of 25-vitamin D to 1,25-vitamin D. It also increases phosphate excretion by the kidney as a result of the increased calcium resorption.

Thus, primary hyperparathyroidism would show increased PTH, increased calcium, and decreased/normal phosphate, which does match this vignette's blood tests. It is usually caused by parathyroid adenomas.

Secondary hyperparathyroidism is an appropriate response to low calcium, for example in renal failure or vitamin D deficiency. It shows high PTH, and low calcium. The phosphate increases, as vitamin D causes phosphate secretion (with deficiency causing the opposite), and renal failure meaing kidneys are unable to excrete phosphate.

Tertiary hyperparathyroidism occurs after the primary defect in secondary hyperparathyroidism is corrected, for example in dialysis. The parathyroid gland continues to produce PTH even after the calcium levels return to normal. It gives the same blood findings as in primary parathyroidism, but with a different history. This is most likely in this case.

91

A 59-year-old man presents with a fall and haematemesis after a heavy night drinking at the local pub. This is his third admission in a month with alcohol-related problems. He has stopped vomiting, and on examination he is haemodynamically stable. He has digital clubbing, spider naevi, and gynaecomastia. He is admitted for neurological observations overnight as he hit his head. The doctors notice the patient suffers from complex opthalmoplegia, confusion and ataxia. Given his neurological symptoms, which test would confirm the associated vitamin deficiency?

A) Red cell folate
B) RBC transketolase
C) RBC glutathione reductase
D) RBC aspartate aminotransferase activity
E) Carbohydrate deficient transferrin

B

This patient is suffering from chronic alcoholism, with the classical triad of Wernicke's encephalopathy (ophthalmoplegia, confusion, and ataxia) caused by a vitamin B1 (thiamine deficiency). The test for this deficiency is RBC transketolase, a thiamine pyrophosphate requiring enzyme. The enzyme activity is measure before and after the addition of thiamine. A large increase signifies a deficiency.

Similar assays are done to test for vitamin B6, pyridoxine, and vitamin B2, riboflavin, with AST and RBC glutathione reductase respectively. B6 deficiency is a side effect of isoniazid use, and should be supplemented alongside the drug.

RBC folate (vitamin B9) measures folic acid levels. Deficiencies cause megaloblastic anaemia and NTDs in pregnancy.

Carbohydrate deficient transferrin is used to detect alcohol abuse.

92

A 75-year-old man presents with acute onset abdominal pain. The patient has not passed stools for 3 days and looks unwell. His past medical history includes bowel cancer which was treated with an abdominoperineal resection and chemotherapy 6 years ago. On examination, there is a large parastomal mass with is tender and irreducible. An arterial blood gas shows metabolic acidosis with raised lactate. The on-call doctor immediately starts normal saline and prepares the patient for theatre. A strangulated hernia is diagnosed by the registrar and an emergency laparotomy is performed to resect the ischaemic bowel. One day postoperatively the patient has the following blood results:

Hb 132
WCC 10.9
Platelets 234
Na 145
K 6.3
pH 7.38
Urea and creatinine normal

A) Acute kidney injury
B) Tissue injury
C) Resolving metabolic acidosis
D) Adrenal failure from metastases
E) Overhydration from intravenous fluids

6 B

K is the principle intracellular cation. Therefore, K rises in tissue injury as cells burst.

AKI is unlikely due to the normal urea and creatinine.

Whilst metabolic acidosis does cause hyperkalaemia, this doesn't last. K+ and H+ ions compete for exchange with sodium, so if there is an acidosis, with high amounts of H+, K+ tends to be left in the extracellular space, and rises. As the acidosis resolves, the hyperkalaemia resolves.

Adrenal failure, or Addison's disease, classically presents with hyperkalaemia, hyponatraemia, and hypercalcaemia.

93

A 54-year-old with a background of hypertension presents to the GP with a 2-week history of diarrhoea. He has been travelling in South East Asia recently and developed symptoms of diarrhoea. He went to the local doctor whilst in China who prescribed tetracycline, but his symptoms have persisted and only improved slightly. His past medical history includes an undisplaced parietal skull fracture he sustained when he was 10. He takes no other medications. The GP orders blood tests which show the following:

Na 148
K 4.8
Urea 13
Creatinine 112

What is the most likely cause of his hypernatraemia?

A) Conn's syndrome
B) Nephrogenic diabetes insipidus
C) Cranial diabetes insipidus
D) Tetracycline
E) Dehydration

E

94

A 42-year-old woman with persistent polyuria and polydipsia is admitted for a water deprivation test. At the beginning of the test, her weight, urine volume and osmolality, and serum osmolality are measured. All are measured hourly thereafter for 8 hours. After 8 hours, she is given intramuscular desmopressin. She drinks 3L of water before going to bed. Her blood is taken again the next morning (16h after beginning the test) and the results are as follows:

Start: weight 70kg, urine vol 0mL, urine osm 278 mosmol/kg

8h: weight 67.8kg, urine vol 2200mL, urine osm 872 mosmol/kg

16h: weight 66.8kg, urine vol 4000mL, urine osm 980 mosmol/kg

What is the most likely diagnosis?

A) Nephrogenic diabetes insipidus
B) Craniogenic diabetes insipidus
C) Psychogenic polydipsia
D) Invalid test
E) Normal

D

95

A 24-year-old previously fit and well woman presents with sudden onset abdominal pain the night after a party where she drank five units of alcohol. She complains of central abdominal pain, with nausea and vomiting. She also finds it difficult to control her bladder. On examination, she is tachycardic, hypertensive, and is beginning to become confused. On looking back at her previous admissions, the doctor notices she has had similar episodes after drinking, and also after starting the oral contraceptive pill. Another similar episode occurred when she had TB and was started on standard antibiotic treatments. She is also seeing a neurologist for peripheral neuropathy of unknown cause. The admitting doctor suggests the possibility of acute intermittent porphyria. What enzyme deficiency is responsible for this disease?

A) Porphobilinogen deaminase
B) Uroporphyrinogen synthase
C) Coproporphyrinogen oxidase
D) Protoporphyrinogen oxidase
E) Uroporphyrinogen decarboxylase

A

96

A patient presents with an acutely painful, inflamed elbow. He has decreased range of movement passively and actively, and the joint is tender, erythematous, and warm. His past medical history includes hypertension, chronic lower back pain for which he takes aspirin, lymphoma for which he has just completed a course of chemotherapy and psoriasis which is well controlled. He is also a heavy drinker. A joint aspirate shows weakly negative birefringent crystals confirming the diagnosis of acute gout. Which factor in this patient is the least likely to contribute to this attack?

A) Bendroflumethiazide
B) Chemotherapy
C) Alcohol
D) Psoriasis
E) Aspirin

D

97

A patient has the following blood results; calculate the anion gap.

Na 143 mmol/L
K 4 mmol/L
Cl 107 mmol/L
HCO3 25 mmol/L
PO4 1 mmol/L
Glucose 8 mmol/L
Urea 7 mmol/L

A) 14 mmol/L
B) 15 mmol/L
C) 16 mmol/L
D) 17 mmol/L
E) Not enough information

E

98

A patient has the following blood results:

Na 143 mmol/L
K 4 mmol/L
Cl 107 mmol/L
HCO3 25 mmol/L
PO4 1 mmol/L
Glucose 8 mmol/L
Urea 7 mmol/L

What is the estimated plasma osmolarity?

A) 309
B) 279
C) 426
D) 294
E) Not enough information

E

99

A 67-year-old man with chronic renal failure presents with fatigue. He has been on haemodialysis 3 times per week for a decade. His past medical history includes diabetes mellitus, hypertension, and gout. He has been increasingly tired the last few weeks although he cannot explain why. He has been attending his dialysis appointments and is compliant with his medications. The GP takes some bloods to investigate. Which of the following is not a common association with chronic renal failure?

A) Acidosis
B) Anaemia
C) Hyperkalaemia
D) Hypocalcaemia
E) Hypophosphataemia

C

100

A 45-year-old woman presents feeling tired all of the time. She has been investigated for anaemia which reveals macrocytosis. She denies drinking excessively. She has recently moved house and the GP notices she has a croaky voice, peaches and cream complexion, and a slowed reaction to his questions. He examines her and elicits slow relaxing ankle reflexes. He suspects hypothyroidism and orders some thyroid function tests. Which of the following results are consistent with primary hypothyroidism?

A) Low TSH, raised free T4 and T3
B) Low or normal TSH with low free T4 and T3
C) Raised TSH with normal free T4 and T3
D) Normal or raised TSH with raised T4 and T3
E) None of the above

E

101

An 86-year-old woman presents to accident and emergency after a fall. She is a frequent faller but was unable to weight bear after the most recent incident. She has a history of rheumatoid arthritis which is controlled with low dose prednisolone. On examination, her right leg is clinically shortened and externally rotated. A pelvic X-ray confirms the presence of a fractured neck of femur. The patient's hip is fixed the next day. Her day one post-operative bloods show the following:

Corrected calcium normal
Phosphate normal
Alkaline phosphate raised
Parathyroid hormone level normal
Vitamin D level low

A) Normal
B) Osteoporosis
C) Paget's disease
D) Osteomalacia
E) Malignancy

D

102

A 42-year-old woman presents to maternity in labour. It is her first child, and she delivers a baby boy at 42 gestation. During the neonatal period, the child develops feeding difficulty with hypotonia and jaundice. On examination, there is a conjugated hyperbilirubinaemia. The mother thinks this has started shortly after she has started feeding the child with milk. After a few months, the child develops cataracts. On testing the urine, there is positive Fehling's and Benedict's reagent tests with a negative glucose oxidase strip test. The milk is eliminated from the child's diet and immediately some of the symptoms improve. What is the diagnosis?

A) Fructose intolerance
B) Galactosaemia
C) Galactokinase deficiency
D) Urea cycle disorder
E) Tyrosinaemia

C

103

A 2-week-old neonate born at term with no gestational complications develops unconjugated jaundice. This was following a difficult birth where instrumentation was required after excessive delay in the second stage of labour. On examination, the neonate looks well, in a normal flexed position with visible jaundice most noticeable in the soft palate. There are no abnormal facies, but there is a visible large caput succedaneum with bruising. Urine dipstick is normal with no markers of infection present in the blood. What is the most likely cause of the jaundice?

A) Urinary tract infection
B) Bruising
C) Haemolysis
D) Crigler-Najjar syndrome
E) Gilbert's disease

B

104

A 54-year-old man with a past history of alcohol abuse, recurrent severe epigastric pain, flatulence, and steatorrhoea presents after a fall whilst out drinking with his friends. He had fallen onto his hip, has severe pain, and inability to weight bear. On examination, his right lower limb is shortened and externally rotated. His liver function tests were normal apart from a raised alkaline phosphatase. A fractured neck of femur is diagnosed and fixed that night. As part of a routine follow-up, the fracture liaison nurse suspects vitamin D deficiency and orders a full set of vitamin D levels. What set of results would you expect in this man given his history?

A) Low 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol, low parathyroid hormone
B) Low 25-hydroxycholecalciferol, high 1,25-dihydroxycholecalciferol, high parathyroid hormone
C) High 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol, high parathyroid hormone
D) High 25-hydroxycholecalciferol, high 1,25-dihydroxycholecalciferol, high parathyroid hormone
E) Low 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol, low parathyroid hormone

A

105

Which of the following is not a cause of raised alkaline phosphatase levels?

A) Pregnancy
B) Paget's
C) Congestive heart failure
D) Obstructive jaundice
E) Myeloma

B

106

A 44-year-old African man is seen by a volunteer doctor in his village with skin changes around the neck. There are erythematous and pigmented areas around the neck in a necklace-like distribution. His family is also complaining of him becoming more forgetful and unable to perform normal daily tasks. This is made particularly distressing given his increase in bowel movements, although he cannot remember how many times he goes. he and his family, like many of the villagers, eat almost exclusively maize, and the doctor has treated several cases of kwashiorkor in the local area. What is the nutritional deficiency most likely to explain his symptoms?

A) Tocopherol
B) Riboflavin
C) Retinol
D) Vitamin B3
E) Ascorbate

D

107

A 51-year-old woman with epilepsy is admitted after suffering a seizure following non-compliance with her phenytoin. She admits to having problems at home and was finding it difficult to continue to take her medication regularly. She is restarted on phenytoin. How many half lives does it normally take for a drug to reach its steady state?

A) 1-2 half lives
B) 3-5 half lives
C) 10-11 half lives
D) 50-60 half lives
E) 100-10 half lives

B

108

A 67-year-old Indian man presents with irritability, sweating, and tremor, which progresses to stupor. The admitting doctor sends for a laboratory glucose which comes back at 2.2 mmol/L. The patient is resuscitated and given intravenous glucose. A history reveals that he does not suffer from diabetes, and his past medical history is remarkable only for vitiligo. On direct questioning, he admits to feeling increasingly more tired, particularly after returning from India. His family arrive after which the doctor notices the patient's unusually darker tan compared with his children. Further investigations reveal the patient has low insulin and low C-peptide concentrations. What is the most likely diagnosis?

A) Pituitary failure
B) Addison's disease
C) Alcohol-induced
D) Glycogen storage disease
E) Medium chain acyl-CoA dehydrogenase deficiency (MCADD)

B

109

A 56-year-old presents with sudden onset, severe epigastric pain which radiates through to the back. The pain is relieved only partly by sitting forward, and is associated with nausea. The admitting doctor suspects pancreatitis and sends for a serum amylase, which is greatly raised. A diagnosis of acute pancreatitis is made. The following blood results come back:

Hb 14.5g/L
WCC 14.2
Na 148
K 4.6
Urea 14
Creatinine 123
Ca 2.98
Cholesterol 5.5
Albumin 35g/L
Glucose 8.8mmol/L

Which biochemical abnormality is not likely to be a consequence of acute pancreatitis?

A) Raised white cells
B) Raised sodium
C) Raised urea and creatinine
D) Raised calcium
E) Raised glucose

A

110

A 76-year-old man presents following a fall, and is diagnosed with a pubic ramus fracture which is treated conservatively. He has a background of chronic renal failure and over the weekend starts to feel palpitations and lightheadedness. An ECG is performed which shows tenting of the T waves, suggestive of hyperkalaemia. A blood test confirms the diagnosis. Which of the following treatments does not lower plasma potassium levels?

A) Calcium resonium
B) Sodium bicarbonate
C) Calcium gluconate
D) Insulin
E) Salbutamol

A

111

A 54-year-old man is admitted for an elective shoulder repair. The day before his surgery he develops acute onset central crushing chest pain radiating to his left arm and up the jaw. He is also sweaty and feel nauseous. He has a past medical history of coronary artery bypass grafting and angina, and his father died from a heart attack aged 46. An ECG is performed, showing acute ST elevation in the inferior leads. He is diagnosed with acute coronary syndrome and treated appropriately. His surgery is delayed, but he presents with the same symptoms 2 days later with further ST changes in the lateral leads. Which cardiac enzyme is most useful to confirm re-infarction?

A) Troponin I
B) Troponin T
C) Aspartate transaminase
D) Creatinine kinase muscle brain (CKMB)
E) Lactate dehydrogenase

B