Blood Physiology & Pathology: MRCEM Primary questions with answers

Blood Physiology & Pathology looks at how blood is made, how it clots and what happens when clotting fails. Physiology carries 60 of the 180 questions in MRCEM Primary. The lessons cover haemopoiesis, haemoglobin, haemostasis, platelets and the platelet plug, the coagulation cascade, hereditary and acquired coagulation disorders, platelet bleeding disorders, and antiplatelet and anticoagulant drugs. This is central to assessing bleeding patients and reversing anticoagulation in emergency care.

5 free questions below, each with the answer and the full explanation · 131 in the full bank · Last updated after the 27 October 2026 MRCEM Primary sitting.

1. Question 1 · Haemoglobin

   A woman aged 35 presents with fatigue and yellow sclera. Blood tests reveal a high bilirubin which is found to be unconjugated bilirubin. Which pathology is the most likely cause of her jaundice?

   1. AHepatocellular carcinoma
   2. BHepatitis
   3. CGallstone in the bile duct
   4. DCarcinoma of the head of the pancreas
   5. ESickle cell disease
   Show answer and explanation

   Answer: E. Sickle cell disease causes haemolysis and unconjugated hyperbilirubinaemia.

   • A: Gives mainly conjugated hyperbilirubinaemia.
   • B: Gives mainly conjugated hyperbilirubinaemia.
   • C: Obstruction raises conjugated bilirubin.
   • D: Obstruction raises conjugated bilirubin.

   Full explanation: Haemoglobin

   Haemoglobin 

   • Red blood cells contain the specialised protein haemoglobin which is responsible for carrying oxygen and carbon dioxide in the blood.  
   • Haemoglobin is composed of four polypeptide globin chains each with its own iron containing haem molecule. 

    Synthesis of Haemoglobin 

   Haemoglobin synthesis occurs in immature red blood cells.  

   • Haem synthesis occurs largely in the mitochondria by a series of biochemical reactions commencing with the condensation of glycine and succinyl coenzyme A under the action of the key rate-limiting enzyme delta-aminolaevulinic acid (ALA) synthase; ultimately protoporphyrin combines with iron in the ferrous (Fe2+) state to form haem.  
   • The globin chains are synthesized by ribosomes in the cytosol. 

   Haemoglobin Degradation 

   • Red cells are destroyed by macrophages in the liver and spleen after 120 days.  
   • The haem group is split from the haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled to plasma via transferrin or stored in macrophages as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in excess bilirubin and jaundice. 

   Types of Hemoglobin 

   There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F. 

   • Fetal HB has high affinity for o2 as compared to adult. 

   Hb	Structure	Normal adult %
   HbA	Two alpha, Two Beta	96 - 98%
   HbA2	Two alpha, Two delta	1.5 - 3.5%
   HbF	Two alpha, Two gamma	0.5-0.8%

2. Question 2 · Blood Physiology & Pathology

   A male aged 60 presents to the ED with fatigue. Lab value reveals anemia, Lymphocytosis, and thrombocytopenia. Which one of the following malignancies is most common in UK?

   1. AAML
   2. BALL
   3. CCML
   4. DHodgkin lymphoma
   5. ECLL
   Show answer and explanation

   Answer: E. CLL is the commonest leukaemia in older adults and gives lymphocytosis, anaemia and thrombocytopenia.

   • A: Myeloid with blasts, not lymphocytosis.
   • B: Mainly children.
   • C: Myeloid; granulocytosis.
   • D: A lymphoma, not leukaemia.

   Full explanation

   Leukemia (High yield)

   1: Acute Leukemia

   AML (Common in Adults)

   Clinical

   • Thrombocytopenia
   • Anemia
   • Neutropenia

   2: ALL (common in Children) Recall

   Greater than > 20% blast cells

   Philadelphia chromosome translocation 9:22

   Clinical

   • Thrombocytopenia
   • Anemia
   • Neutropenia
   • Lymph adenopathy
   • Splenohepatomegaly
   • CNS involvement

    

   Chronic Leukemia

   1: CML (15% leukemia) (40-60 years peak age)

   Dx = 98% Philadelphia chromosome

   Mature myelocytes but a greater amount

   Clinical

   • Anemia
   • Thrombocytes greater or less
   • WBC greater
   • Basophilia
   • Splenomegaly

   2: CLL =} 60-80 years overall most common also in UK

   Lymphocyte mature function abnormally

   Clinical

   • Fatigue most common symptom
   • Lymphadenopathy
   • Lymphocytosis
   • Thrombocytopenia
   • Anemia
   • Bone marrow biopsy smudge cells

    

   Multiple myeloma:

   Neoplastic disease characterized by plasma cell accumulation in bone marrow

   Useful mnemonic OLD-CRAB

   • Old age usually in 60-70
   • hypercalcemia
   • Renal impairment
   • Anemia
   • Bone pain

   Note IgG (60% Cases and IgA (20% Cases) are the immunoglobulins most often found in high amounts in people with multiple myeloma.

3. Question 3 · Acquired Coagulation Disorder of Blood

   A patient with a known history of poorly controlled diabetes mellitus attends with fatigue and dizziness. Routine tests show a normocytic normochromic anaemia. What is the most likely underlying cause?

   1. AVitamin B12 deficiency
   2. BIron deficiency
   3. CHaemolysis
   4. DDecreased erythropoietin
   5. EDecreased hepcidin
   Show answer and explanation

   Answer: D. Diabetic kidney disease reduces renal erythropoietin synthesis, causing normocytic normochromic anaemia.

   • A: Causes macrocytic anaemia.
   • B: Causes microcytic anaemia.
   • C: Haemolysis would give raised bilirubin and reticulocytes.
   • E: Hepcidin is raised, not lowered, in inflammatory or chronic disease anaemia.

   Full explanation: Anaemia Overview

   Anaemia is defined as a reduction in haemoglobin concentration below the normal range for the age and sex of the individual. Women tend to have lower haemoglobin than men.

   Normal Values

   Although laboratory values vary, typical values would be less than 135 g/L in adult males and less than 115 g/L in adult females. From the age of 2 years to puberty, less than 110 g/L indicates anaemia, and at birth less than 140 g/L indicates anaemia.

   Anaemia may occur from an actual reduction in total circulating haemoglobin mass, or with an increase in plasma volume e.g. in pregnancy, causing a dilutional anaemia. Likewise, a reduction in plasma volume may mask anaemia or even cause an apparent polycythaemia. After acute major blood loss, anaemia is not immediately apparent because total blood volume is reduced and it takes up to a day for plasma volume to be replaced and hence the degree of anaemia to become apparent. The initial clinical features in acute haemorrhage are therefore a result of reduction in blood volume rather than that of anaemia.

   Clinical Features

   When anaemia develops slowly, the associated symptoms are often very mild as the body has time to adapt to the fall in haemoglobin. This involves mechanisms such as an increase in red cell 2,3 -diphosphoglycerate (2,3 - DPG), which shifts the oxygen dissociation curve to the right, allowing enhanced delivery of O₂ to the tissues, and an increase in stroke volume and heart rate.

   In acute onset anaemia, a lack of physiological adaptation leads to more marked symptoms and signs. Significant symptoms may also occur in more mild anaemia in older patients with impaired cardiovascular reserve.

   Non-specific symptoms of anaemia include:

   • fatigue
   • dizziness
   • headache
   • palpitations
   • tinnitus
   • shortness of breath on exertion
   • worsening of angina, congestive heart failure or intermittent claudication

   Non-specific signs of anaemia include:

   • pallor of mucous membranes or nail beds (if Hb < 90 g/L)
   • tachycardia
   • bounding pulse
   • wide pulse pressure
   • flow murmurs
   • cardiomegaly
   • in severe cases, signs of congestive cardiac failure

   Causes

   Anaemia can be classified according to the red cell size or mean cell volume (MCV), into microcytic, normocytic and macrocytic anaemia. This classification is not perfect, as some conditions can straddle two categories e.g. anaemia of chronic disease is usually normocytic, but may be microcytic or there may be combined macrocytic and microcytic causes cancelling each other out to produce an apparent normocytic anaemia.

   • Microcytic anaemia (MCV < 78 fl)
     • Iron deficiency
     • Thalassaemia
     • Other haemoglobin defects
     • Anaemia of chronic disease (some cases)
     • Congenital sideroblastic anaemia
   • Normocytic anaemia (MCV 78 - 98 fl)
     • Most haemolytic anaemias
     • Anaemia of chronic disease (most cases)
     • Mixed cases
   • Macrocytic anaemia (MCV > 98 fl)
     • Megaloblastic anaemia
       • Vitamin B12 deficiency
       • Folate deficiency
     • Other causes
       • Alcohol, liver disease, hypothyroidism, reticulocytosis, cytotoxic drugs, aplastic anaemia, pregnancy, myelodysplastic syndromes, myeloma, neonatal macrocytosis

   Typical Investigations

   • Full blood count
   • Stained blood film
   • Haemoglobin electrophoresis or high performance liquid chromatography (HPLC)
   • Haematinic levels (B12, folate, ferritin, iron and iron-binding capacity)

4. Question 4 · Plateletes Bleeding Disorder

   Which of the following is NOT primarily characterised by intravascular haemolysis:

   1. AThrombotic thrombocytopenic purpura
   2. BGlucose-6-phosphate dehydrogenase deficiency
   3. CBeta-Thalassaemia
   4. DHaemolytic transfusion reactions
   5. EParoxysmal nocturnal haemoglobinuria
   Show answer and explanation

   Answer: C. Beta-thalassaemia major causes mainly extravascular haemolysis.

   • A: Fragmentation causes intravascular haemolysis.
   • B: Intravascular.
   • D: Intravascular.
   • E: Intravascular.

   Full explanation: Plateletes Bleeding Disorder

   Platelets bleeding disorder

   Thrombocytopenia or abnormal platelet function is characterized by spontaneous skin purpura, mucosal haemorrhage and prolonged bleeding after trauma. 

   Important to note here difference between TTP and haemolytic uremic syndrome.

   Immune Thrombocytopenic Purpura or idiopathic

   Thrombotic Thrombocytopaenic Purpura

   Acute ITP is most common in children. In approximately 75% of cases, the episode follows vaccination or infection such as chicken pox or glandular fever Chronic ITP: More prevalent in adults Female to male ratio 3:1 More likely to have underlying autoimmune disease. Example: In patients with thrombocytopaenia, normal haemoglobin, white cell counts, and normal coagulation tests (PT, APTT and fibrinogen) most likely go with ITP

   TTP has traditionally been described as a pentad of Thrombocytopaenia Microangiopathic haemolytic anaemia Neurological abnormalities Renal failure Fever Laboratory Findings: Normal PT/APTT and fibrinogen Decreased platelets

   Note: Difference between TTP and haemolytic uremic syndrome

   TTP	HUS
   Adults—20-50	Children <5 years old
   Pentad	Tetrad
   Hemolytic anemia with RBC fragmentation	Hemolytic anemia with RBC fragmentation
   Renal dysfunction	Acute renal failure
   Thrombocytopenia (35,000)	Thrombocytopenia (95,000)
   Severe CNS symptoms	Mild CNS symptoms
   Fever

    

5. Question 5 · Platelet and Platelet Plug

   Aspirin acts as an antiplatelet drug by inhibiting the synthesis of:

   1. ALeukotriene B4 (LTB4)
   2. BThromboxane A2 (TxA2)
   3. CNitric oxide (NO)
   4. DProstaglandin I2 (PGI2)
   5. EAdenosine diphosphate (ADP)
   Show answer and explanation

   Answer: B. Aspirin blocks COX, reducing thromboxane A2 synthesis.

   • A: Not an aspirin target.
   • C: Not the antiplatelet mechanism.
   • D: Prostacyclin inhibits platelets; its loss is not the antiplatelet action.
   • E: ADP is blocked by clopidogrel.

   Full explanation: Platelet and Platelet Plug

   Platelets and platelet plug 

   Platelets:

   These are minute, round or oval discs formed by fragmentation of megakaryocytes. The normal half-life of platelets is 10 days. 

    Platelets contain three types of storage granules.

   • dense granules containing ADP, ATP, serotonin and calcium.
   • alpha granules containing clotting factors, von Willebrand factor (VWF), platelet-derived growth factor (PDGF) and other proteins. 
   • lysosomes containing hydrolytic enzymes. 

   Functional characteristics of platelets: 

   •  Have no nucleus, so cannot reproduce. 
   •  Have actin and myosin molecules and thrombosthenin, so can contract to cause clot retraction. 
   •  Have residual ER and Golgi apparatus to synthesize enzymes and to store Ca ions.  
   •  Have enzyme systems to synthesize ATP from ADP.  
   •  Have enzyme Systems to synthesize prostaglandins. 
   •  Have fibrin-stabilizing factor that causes polymerization of fibrin monomers to form fibrin threads. 
   •  Have growth factor that promote growth and multiplication of vascular endothelial cells, vascular smooth muscle cells and fibroblasts. So, repair damaged vascular wall. 
   •  Its surface has a glycoprotein-coat that adheres it to injured endothelial cells and exposed collagen fibers form deeper vessel wall. 
   •  Its membrane has phospholipids that activates intrinsic system of blood doting. 
   • Its membrane has Adenyl Cyclase that causes formation of cyclic AMP that excites other activities of platelets. 

   Formation of Platelet Plug  

   • Platelets get adhered to the collagen of ruptured blood vessel and secrete adenosine diphosphate (ADP) and thromboxane A2. These two substances attract more and more platelets and activate them. All these platelets aggregate together and form a loose temporary platelet plug or temporary hemostatic plug, which closes the ruptured vessel and prevents further blood loss. 
   • Platelet aggregation is accelerated by platelet activating factor (PAF) 

   Importance: 

   Platelet plug is important to close small rents in vessel wall. 

   Natural Inhibitors of Platelet Function 

   • The release reaction is inhibited by substances that increase the level of platelet cAMP.  
   • Prostacyclin (PGI2), synthesized by endothelial cells, is one such substance, has the opposing effects of TXA2; it is a potent inhibitor of platelet adhesion and aggregation on normal vascular endothelium (and a potent vasodilator). 
   •  Nitric oxide is constitutively released from endothelial cells and also from macrophages and platelets; it inhibits platelet activation and promotes vasodilation. 

    

   Anti-clotting factor:

   Surface of the cell: Cell membrane is covered by the glycocalyx (it makes the cell surface slippery), clotting factor slip the cell surface and move forward.  

   Antithrombin III: It prevents to convert the prothrombin to thrombin. 

   • Inactivates the already made thrombin.    

   Protein C and Protein S formed by liver 

   • Prevent to convert the prothrombin to thrombin. 
   • Prevent to convert the fibrinogen to fibrin. 

   Heparin: It increases the activity of antithrombin III by 1000 times

   Plasmin:  It breaks already formed clot.  

   • Released by all the tissues.  
   • Convert the inactive plasminogen to plasmin.