HIS Important Questions Flashcards by 888 😉

[Self-assessment]
What is the expected bone marrow cellularity of a person aged 50 years old?
A. 60-80%
B. 50-70%
C. 40-60%

Bone marrow cellularity
= ratio of haematopoietic cells to adipocytes
% cellularity = 100 - Age +/- 10

Newborns, infants: up to 100%, may be lower
Child: 60-80%
Young adults: 50-70%
Adults: 40-60%
Elderly: 25-40%

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[Self-assessment]
What type of capillary is found in bone marrow?
A. Continuous
B. Sinusoidal
C. Fenestrated

Part of vascular components of bone marrow
- deliver products of haematopoiesis away
- arise from vessels at the junction of compact & spongy bone
- connected to nutrient arteries
- drains into 1) central sinus & 2) emissary veins
- endothelial lining + discontinuous BM + incomplete covering of reticular cells

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[Self-assessment]
Polychromatic erythroblasts are so named because their cytoplasm displays both acidophilia and basophilia. What is responsible for basophilia?
A. Haemoglobin
B. Ribosomes
C. Nucleus

Acidophilia: haemoglobin

Proerythroblasts, basophilic erythroblasts: basophilic
Polychromatophilic erythroblasts: polychromatic
Orthochromatophilic erythroblasts, reticulocytes: acidophilic

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[Self-assessment]
A 57-year-old male is diagnosed with essential thrombocytosis. Which cell in his bone marrow is increased in number?
A. Megakaryoblast
B. Platelet
C. Megakaryocyte

Platelets: in circulation
Megakaryoblasts, megakaryocytes: in bone marrow

Essential thrombocytosis:
- benign myeloproliferative disorder
- overproduction of large, non-functional platelets
- increased thrombopoietin +/- megakaryocytes
Tx: control symptoms (headache, enlarged spleen, bleeding from gums, nose, GI tract), anti-cancer agents to maintain proper platelet count

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[Self-assessment]
At which stage of granulopoiesis are specific granules first produced?
A. Promyelocyte
B. Myeloblast
C. Myelocyte

Myeloblasts (progenitor stem cells): X granules

Promyelocytes (precursor cells): azurophilic (primary / non-specific) granules

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[Self-assessment]
In which haematopoietic cell, the nucleus is horseshoe-shaped?
A. Metamyelocyte
B. Band cell
C. Promonocyte

Metamyelocyte: clearly indented nucleus
Band cell: horseshoe-shaped nucleus
Promonocyte: slightly indented nucleus

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[PP]
What is the earliest red cell precursor that can be identified morphologically in the bone marrow?
A. Basophilic erythroblast
B. Orthochromatophilic erythroblast
C. Polychromatophilic erythroblast
D. Proerythroblast
E. Reticulocyte

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[PP]
During examination of a human blood smear, an increased number of eosinophils is found. What is the primary function of eosinophils?
A. Defends against bacterial infections
B. Defends against parasitic infections
C. Presents antigens
D. Release histamine

Present antigens: dendritic cells, macrophages, B cells
Release histamine: basophils, mast cells

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[PP]
Which cell contains the highest density of ribosomes?
A. Basophilic erythroblast
B. Orthochromatophilic erythroblast
C. Polychromatophilic erythroblast
D. Proerythroblast

Basophilic erythroblast:
- most intensely basophilic cytoplasm due to highest density of ribosomes
- NO nucleoli => stop ribosome production

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[Old PP]
Young girl was presented to the hospital after severe asthma attack. Complete blood test was ordered. Which of the following cells is responsible for secreting heparin and histamine?
A. Eosinophil
B. Basophil
C. Neutrophil
D. Monocyte
E. Platelet

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[Old PP]
The bone marrow has formed substances. Which of the following has rRNA residues?
A. Basophil
B. Erythrocyte
C. Megakaryocyte
D. Monocyte
E. Reticulocyte

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[Old PP]
Erythrocytes need to pass through blood capillaries and sinusoids to deliver oxygen to tissues. Which of the following characteristics of erythrocytes contributes to their resilience and durability?
A. Devoid of organelles
B. Glycolipid on plasma membrane
C. Haemoglobin molecules
D. Presence of spectrin and actin
E. Small in size

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[Old PP]
Platelets play a major part in blood coagulation. What is the precursor for platelets?
A. Blastomere
B. Megakaryocyte
C. Monoblast
D. Myeloblast
E. Thrombocyte

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[Old PP]
Mast cells and basophils are the effector cells for immediate hypersensitivity response. What are the major roles of basophils and mast cells?
A. They secrete chemicals to attract macrophages to the site
B. They secrete heparin to restrict blood flow
C. They secrete histamine to promote blood flow
D. They secrete histamine to restrict blood flow
E. They secrete lysozymes to promote blood flow

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[Old PP]
Neutrophils are the most abundant white blood cells in peripheral blood content and they increase their numbers during acute inflammation. Under what circumstances will there most likely be the highest rise in neutrophil concentration in the plasma?
A. Allergy
B. Bacterial infection
C. Parasitic infection
D. Low blood oxygen
E. Yeast infection

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[Old PP]
Histamine is a vasodilator that dilates blood vessels making them more permeable to white blood cells and other proteins. Which of the following immunological cell types secretes histamine in an acute inflammatory response?
A. Basophil
B. Eosinophil
C. Monocyte
D. Neutrophil
E. Platelet

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[Old PP]
What is the expected white blood cell change in peripheral blood in systemic bacterial infection in adults?

Neutrophilia

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[Old PP]
What is the expected white blood cell change in peripheral blood in viral infection in children?

Lymphocytosis

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[Old PP]
What is the expected white blood cell change in peripheral blood in chronic TB infection?

Monocytosis

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[Old PP]
What is the expected white blood cell change in HIV infection?

Lymphopenia

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[Old PP]
What is the expected white blood cell change in chronic allergic skin disease?

Eosinophilia

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[Old PP]
Blood is classified as a type of connective tissue and consist of two main components, namely plasma and formed elements. Which of the following formed elements is a cell fragment?
A. Globulin
B. Lymphocytes
C. Monocytes
D. Platelets
E. Red blood cells

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[Old PP]
Tommy, a lab assistant, cut his finger while handling a microbiological specimen, which of the following responses will most likely occur within 12 hours?
A. Neutrophils phagocytose the bacteria
B. NK cells are activated to kill the bacteria
C. Interferons are produced to kill the bacteria directly
D. Antibodies are created to destroy the bacteria
E. Macrophages ingest the foreign body

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[Old PP]
In a normal adult, where can hematopoietic elements be found?
A. Aorta
B. Lymph node
C. Liver
D. Spleen
E. Sternum

Vertebrae > sternum > ribs > femur > tibia

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[Old PP] There are fat cells and haematopoietic stem cells in the bone marrow in medullary cavity of long bones. Which of the following elements is supporting cell for haematopoiesis? A. Adipocyte B. Megakaryocyte C. Erythrocyte D. Adventitial reticular cell E. Sinusoidal epithelial cell

[Old PP] A certain type of immature cells remain in the blood circulation for 3 days and then enters tissues, differentiating into another cell type which is involved in phagocytosis of pathogens, foreign bodies, etc. Whatbis the immature cell type? A. Endothelial cell B. Histiocytes C. Macrophage D. Monocyte E. Plasma cells

[Old PP] Red bone marrow in medullary cavity of flat bones and head of long bones is a major site of haematopoiesis. Which of the following elements is a non-stromal cell in red bone marrow? A. Endothelial cell B. Fat-storing cell C. Macrophage D. Myeloblast E. Reticular cell

[Old PP] Which of the following is not stromal cells of red bone marrow? A. Fat-storing cells B. Endothelial cells C. Myelocytes D. Fibroblasts

[Old PP] What is the most important property of haematopoietic stem cells which enables them to sustain red cell production throughout life? A. Apoptosis B. Differentiation C. Dormancy D. Proliferation E. Self-renewal

[Old PP] Which of the following is NOT essential for haematopoiesis in the bone marrow? A. Extracellular matrix B. Normal splenic function C. Stromal cells D. Topography of the bone marrow E. Vascular network

[Old PP] What substance persists in the cytoplasm of red blood cells which makes them identifiable as reticulocytes in peripheral blood? A. Haemoglobin B. RNA C. Mitochondria D. Rough endoplasmic reticulum E. Golgi apparatus

[Old PP] Which of the following in blood cells in INCORRECT? A. Increase in neutrophil count is usually due to acute infection such as appendicitis B. Granules of eosinophils contain enzymes that are particularly effective against parasitic worms in their larval form C. Granules of basophils contain histamine and heparin D. Monocytes are non-phagocytes and defend the body against viruses and bacteria E. Platelets derived from megakaryocytes are important for proper blood clotting

[Old PP] When a bacterium is phagocytosed by a neutrophil, the cell organelle that contains a number of hydrolytic enzymes to destroy the bacteria is the A. Centriole B. Golgi apparatus C. Lysosome D. Mitochondria E. Ribosome

[Old PP] Name a major function of neutrophils. They may contain a histological structure known as Barr body, what is it?

As a phagocyte in acute inflammation, especially bacterial infections Inactivated X chromosomes visible in female somatic cells like neutrophils

[Old PP] Which of the following is LEAST likely a property of macrophages? A. The macrophage is derived from a monocyte B. The macrophage phagocytoses apoptotic cells C. The macrophage secretes interleukin-1 D. The macrophage produces IgG E. The macrophage has a kidney-shaped nucleus

[Old PP] Which of the following is NOT a function of macrophages? A. Antigen presentation B. Phagocytosis C. Production of immunoglobulin D. Secretion of IL-1 E. Secretion of TNF-alpha

[Old PP] Mrs. Kwok has lobar pneumonia due to pneumococcus. Which cell type is MOST likely present in the exudate? A. Eosinophils B. Lymphocytes C. Macrophages D. Neutrophils E. Plasma cells

[Old PP] Which of the following is NOT considered a feature of neutrophils? A. They are motile B. They are the main cell type involved in dealing with bacteria C. They contain specific granules D. They phagocytose E. They secrete TNF-alpha

[Old PP] The lifespan of an adult red blood cell is USUALLY considered to be: A. 1 month B. 2 months C. 4 months D. 6 months E. 10 months

[Old PP] Which of the following cells are crucial to the development of specific or acquired immune system in humans? A. Eosinophils B. Lymphocytes C. Neutrophils D. Platelets E. Red blood cells

[Old PP] Which of the following cell types characteristically LACKS a nucleus? A. Eosinophils B. Megakaryocyte C. Monocytes D. Neutrophils E. Platelets

E Short half-life, cannot replace substances inactivated by aspirin

[PP] Ionic iron is kept in a non-toxic state to cells through multiple biochemical mechanisms. Formation of which of the following complexes makes iron ion a relatively safe molecular species when it is stored in cells? A. Fe2+/ferritin complex B. Fe2+/porphyrin complex C. Fe3+/glutathione complex D. Fe3+/transferrin complex

[PP] Hepcidin is a protein secreted by the liver to regulate iron homeostasis in the human body. How does hepcidin control the absorption of dietary iron? A. Decreases the number of intestinal cells that express transferrin receptors B. Increases the rate of degradation of ferroportin C. Inhibits the degradation of haem within intestinal cells D. Stimulates the export of iron from intestinal cells for removal in faeces E. Stimulates the synthesis of ferroxidase

B Increased hepcidin secreted by liver => bind to ferroportin (FPN) => internalisation & degradation => reduced Fe3+ released as transferrin to blood by duodenal enterocytes, macrophages & hepatocytes

[PP] Degradation products of the haem molecule can be eliminated from the human body via the faecal as well as the urinary route. Which biochemical reaction is responsible for channelling haem degradation products for excretion by the urinary route? A. Glucuronidation in kidney medulla B. Glucuronidation in liver C. Oxidation in splenic macrophages D. Reduction in intestine

D Urobilinogen (final degradation product, normally low in urine) is formed by microbial enzymes in intestine

[Self-assessment] Why does frequent blood transfusion result in iron overload? A. Iron is not excretable B. Iron is easily absorbed into body cells C. Blood transfusion stimulates the uptake of iron from diet

A Accumulation of red blood cells and transferrin

[Self-assessment] What is the status of iron when it is stored intracellularly? A. Fe3+ in hemopexin B. Fe2+ in ferritin C. Fe2+ in transferrin

B Hemopexin: transport heme iron in blood Transferrin: transport Fe3+ in blood

[Self-assessment] Which of the following describes the function of transferrin? A. It can translocate iron from intracellular to extracellular space B. It can transport Fe3+ in blood C. It can store iron extra cellular

B Degradation of ferritin to give Fe2+ => Export of Fe2+ by ferroportin (FPN) => oxidation to Fe3+ by ferroxidase (FeOx) => transport by transferrin

[Self-assessment] Which of the following cells gives iron to developing red blood cells in bone marrow? A. Monocyte B. Macrophage C. Neutrophil

B Developing erythroblast => nucleus & mitochondria transferred to central nurse macrophage => iron store built up in macrophage releases Fe3+ to erythroblasts => build up heme & hemoglobin

[Self-assessment] Which of the following proteins immediately controls the release of iron through ferroportin? A. Ferritin B. Hemopexin C. Hepcidin

[PP] In response to antigen stimulation, T cells exhibit unique features of adaptive immunity. Which of the following is a KEY feature of adaptive immunity? A. Activation B. Cytotoxicity C. Differentiation D. Specificity

[PP] In response to viral infections, B cells exhibit unique features of adaptive immunity. Which of the following is a key feature of B cell response? A. Antigen recognition B. Cytokine production C. Cytotoxic activity D. Phagocytic process

[PP] The specific immunity (adaptive immunity) is mediated by T and B lymphocytes upon antigenic exposure. Which of the following soluble factors are produced during development of specific immunity? A. Acute phase proteins B. Chemokine receptors C. Neutralising antibodies D. T cell receptors

[PP] Specific immune responses act as host defences that are mediated by H and T cells following exposure to antigens. Describe specificity as a feature of specific immunity.

B, T lymphocytes express specific membrane receptors that distinguish between distinct antigens => immune responses = specific for distinct antigens (e.g. neutralising antibodies)

[PP] Describe diversity as a feature of specific immunity.

Gene rearrangement => an individual generates numerous different clones of lymphocytes => lymphocytes in mammalian immune system can discriminate at least 10^9 distinct antigens

[PP] Describe (immunological) memory as a feature of specific immunity.

Exposure of immune system to a foreign antigen => formation of memory B and T cells by clonal selection and expansion => enhance ability to response to that specific antigen => secondary immune response = more rapid, stronger

[PP] Describe self-regulation as a feature of specific immunity.

All normal immune responses wane with time after antigenic stimulation e.g. Activation-induced cell death Failure of lymphocytic apoptosis => defective homeostasis (e.g. lung infection in HIV patients)

[PP] Describe discrimination of self from non-self as a feature of specific immunity.

Immune system can distinguish between foreign antigen and self-antigen Lymphocytes - can recognise and respond to foreign antigens - but normally unresponsive to self-antigens (tolerance) mediated by dendritic cells E.g. foetus: distinguish between maternal & foreign material

[Old PP] What are the five major features of adaptive immune response?

1. Specificity 2. Diversity 3. (Immunological) memory 4. Self-regulation 5. Discrimination of self from non-self

[Old PP] Describe clonal selection hypothesis.

1. Specificity: An immunologically competent B / T lymphocyte expresses surface receptors for a single antigenic epitope (i.e. all receptors on one cell are identical) 2. Antigenic stimulation, clonal selection - When the host is exposed to an antigen, the antigenic epitopes will bind specifically to B / T cells with complementary receptors to induce 3. Clonal expansion = proliferation of these lymphocytes into clones of identical cells (surface receptors with same specificity / binding site) - B cells mature into plasma cells (effector cells) secreting antibodies (same specificity as surface receptors on parent B cell) OR memory cells (also same antigen specificity) 4. Tolerance induction - Embryonic development: contact between B / T cells & antigens they are specific for => destruction of that clone = delete / suppress autoreactive B / T cells => antigen-specific non-responsiveness

[Old PP] Research has indicated that an inextricable link exists between our emotions, which includes all stress in our lives, both good and bad, and regulatory mechanisms of immune systems through central nervous system. Suggest 5 psychosocial factors which may alter the immune system.

1. Optimistic / Pessimistic 2. Social support which affects sense of stability & coping resources 3. Confidence in coping with stress 4. Perceived control over stressors 5. Physical activity 6. Hardiness (desire to accept challenges) 7. Financial crisis 8. Chronic stressful conditions

[PP] What is the MOST SPECIFIC laboratory feature for autoimmune haemolytic anaemia? A. Conjugated hyperbilirubinaemia B. Low reticulocyte count C. Positive direct antiglobulin test D. Red cell fragmentation E. Spherocytosis

C Direct Coombs test

[PP] A 28-year-old man presented with fever. His complete blood count showed WCC 0.1*10^9/L (Normal: 3.2-9.6*10^9/L). Physical examination showed pallor and generalised petechiae. What is the MOST LIKELY diagnosis of the patient? A. Aplastic anaemia B. Haemolytic anaemia due to G6PD deficiency C. Idiopathic thrombocytopaenia purpura D. Pure red cell aplasia

[PP] A 70-year-old man with good past health presented with fatigue and dyspnoea. His complete blood count showed: Lowered white blood cell Lowered haemoglobin Elevated mean corpuscular volume Lowered platelet count Lowered reticulocyte count His peripheral blood film showed marked anisopoikilocytosis with macrocytes, macro ovalocytes, and a few hypersegmented neutrophils. Blasts were not evident. Which of the following is the MOST LIKELY cause of the abnormalities? A. Acute leukaemia B. Myelodysplastic syndrome (MDS) C. Pernicious anaemia D. Thrombotic thrombocytopenic purpura (TTP)

C Vitamin B12 deficiency -> pernicious anaemia (pancytopenia, macro-ovalocytes, hypersegmented neutrophils) Folate deficiency: unlikely to cause severe pancytopenia & hypersegmented neutrophils - usually causes mild macrocytic anaemia

[PP] A 50-year-old man presented with shortness of breath. Hypersegmented neutrophils were seen in the peripheral blood film. What is the haematological diagnosis of the patient?

Megaloblastic anaemia

[PP] Following peripheral blood film examination, what is the next step of investigation to confirm the diagnosis of megaloblastic anaemia?

Serum active vitamin B12 level

[PP] Name one non-haematological clinical manifestation of megaloblastic anaemia.

1. Vitamin B12 neuropathy: - peripheral neuropathy, optic atrophy, dementia, subacute combined degeneration of cord (dorsal & lateral columns) - may occur without haematological changes 2. Mild jaundice (lemon yellow tint) 3. Glossitis, angular stomatitis

[PP] Why is a patient with megaloblastic anaemia having shortness of breath?

Cardiopulmonary compensation in response to tissue hypoxia Many large, immature & dysfunctional RBCs in bone marrow, low [Hb] => impaired O2 transport => tissue hypoxia

[PP] For the following lymphomas, which one has the HIGHEST annual incidence in adults in Hong Kong? A. B cell lymphoma B. Hodgkin lymphoma C. NK cell lymphoma D. T cell lymphoma

[PP] The production of platelets is regulated by the hormone thrombopoietin. Which of the following organs releases this hormone? A. Bone marrow B. Liver C. Pituitary gland D. Suprarenal gland

B Erythropoietin: kidney

[PP] Newborn babies receive passive immunity through breastfeeding. Which of the following antibody isotypes is enriched in breast milk? A. IgA B. IgE C. IgG D. IgM

A IgA dimers with J chain, can be transported across epithelium for mucosal secretion

[PP] B cell development takes place in the bone marrow, which can be divided into various differentiation stages. The negative selection is a process of deleting autoreactive B cells. At which of the following B cell differentiation stages does this selection process occur? A. Follicular B cells B. Immature B cells C. Memory B cells D. Progenitor B cells

[PP] B cell development takes place in the bone marrow during postnatal life. Which of the following events occurs during B cell development? A. Antibody affinity maturation B. Immunoglobulin class switching C. Immunoglobulin gene recombination D. T cell receptor gene rearrangement

[PP] In response to antigen stimulation, activated B cells produce antibodies. One IgM molecule consists of which of the following components? A. Two antigen binding sites B. Two constant regions C. Two disulphide bonds D. Two variable regions

[PP] During the humoral immune response, B cells differentiate into plasma cells for antibody production. Which of the following is/are found as structural component(s) of an antibody molecule? A. One constant region B. One variable region C. Two antigen-binding sites D. Two different heavy chains

[PP] Which of the following directly involves collaboration between innate and adaptive immunity? A. Antibody production B. Complement activation C. Natural killer cell activation D. Plasma cell generation E. T cell differentiation

[PP] Mr. Leung, due to a genetic mutation, has abnormally high level of IgM but reduced level of IgG. Which of the following components of the immune system is impaired by this mutation? A. Complement B. CD4+ T cells C. CD8+ T cells D. Natural killer cells

[PP] After stimulation by a polysaccharide antigen, a clone of naive B cells is differentiated into plasma cells. Which antibody isotype is MOST LIKELY produced by these plasma cells? A. IgA B. IgE C. IgG D. IgM

D Polysaccharide antigens are thymus-independent (TI) antigens

[PP] Our immune system can recognise and eliminate specific pathogens. The genes encoding of which of the following can undergo hypermutation to create receptors that are an even better fit for foreign antigens? A. B cell receptors B. Complement receptors C. Fc receptors D. T cell receptors

[Old PP] One woman, farmer, from Cambodia, previously diagnosed of Grave’s disease, given carbimazole, thyroid function test was normal in the subsequent 5 years. Presents with menorrhagia, fever 39 degrees, red dots on skin, petechiae, CBC results are shown below. HGB: 5.0 g/dL MCV: 65 fL RDW: 17% RBC: 2.5*10^12/L Physical examination shows no splenomegaly, no lymph node enlargement. What is the most likely diagnosis for her anaemia? A. Aplastic anaemia B. HbH disease C. Iron deficiency anaemia D. Mixed iron deficiency anaemia with thalassaemia trait E. Pure red cell aplasia due to parvovirus infection

AP Pancytopenia (low Hb, fever, petechiae) - Aplastic -> thrombocytopenia -> petechiae HbH disease & iron deficiency cannot explain all S/S Pure red cell aplasia only affects the red cell lineage Microcytic anaemia: Fe deficiency due to menorrhagia, due to low platelet count

[Old PP] MCV equation A. Haemoglobin / red cell count B. Packed red cell volume / haemoglobin concentration C. Packed red cell volume / RBC D. RBC / packed red cell volume

C MCV (mean corpuscular / cell volume) = hematocrit (Hct, volume of blood * proportion of blood that is cellular) / RBC

[Old PP] A 30-year-old man is found with mild hypochromic microcytic anaemia in routine health check blood test. Serum iron profile is normal. What is the next step of investigation? A. Bone marrow examination to look for aplastic anaemia B. Cytogenetics study to detect constitutional chromosomal changes C. Direct antiglobulin test to confirm autoimmune haemolytic anaemia D. Haemoglobin study to investigate for thalassaemia E. Serum B12 and serum folate study to exclude megaloblastic anaemia

D Thalassaemia

[Old PP] Haematological findings of a hemighost, what is the most likely case? A. 2-year-old girl who takes fava bean B. 30-year-old Chinese man who took cotrimoxazole for urinary tract infection C. 35-year-old Chinese pregnant woman who ate Chinese herbal medicine D. 40-year-old European man who takes steroid and rituximab for lymphoma E. Newborn Italian girl with neonatal jaundice

B Sulfonamide (sulfamethoxazole in cotrimoxazole) -> oxidative stress Enzymopathies (non-immune haemolytic anaemia) - oxidative haemolysis e.g. G6PD deficiency (G6PD generates reducing power, X-linked, esp. African / Mediterranean population) - bite cells, hemighosts (Hb contracted to one pole leaving an empty area at opp. pole, arise due to Hb damage), Heinz bodies

[Old PP] Iron deficiency is a common cause of anaemia in Hong Kong. What is the MOST LIKELY mechanism to explain iron deficiency of a 40-year-old man with iron deficiency anaemia? A. Blood loss B. Drug-induced C. Haemochromatosis D. Malabsorption E. Poor oral intake

[Old PP] Sickle cell anaemia is caused by mutation in the beta globin gene. It includes the restriction site of restriction endonuclease MstII. PCR is done to determine the genotype with a set of primers and later processed with the restriction enzyme. For a heterozygous individual how many bands can be seen?

Three 2 smaller bands from digested normal allele 1 larger band from undigested mutant allele

[Old PP] Patients receiving blood transfusion requires blood checking every 2 to 4 months to prevent iron overload. Which of the plasma proteins is elevated in iron overload? A. Deltaaminolevulinic acid synthetase B. Ferritin C. Ferrochelatase D. Glutathione peroxidase E. Transferrin

[Old PP] What is the characteristic of red cells in iron deficiency anaemia? Size? Colour?

Microcytic, hypochromic

[Old PP] What is the probability that a daughter inherited the gene mutation from a father with G6PD deficiency?

100% Both AIHA and hereditary spherocytosis show high osmotic fragility

[Old PP] Although cobalamin takes part in two metabolic pathways only, deficiency in cobalamin will lead to severe diseases. A deficiency of cobalamin will MOST LIKELY lead to which of the following? A. Glycogen storage disease B. Hyperlipidaemia C. Liver cirrhosis D. Megaloblastic anaemia E. Phenylketonuria

[Old PP] Which of the following kinds of mosquitoes spreads malaria? A. Culiseta B. Anopheles C. Aedes D. Topomyia E. Mansonia

[Old PP] A. Aplastic anaemia B. Autoimmune haemolytic anaemia C. Glucose-6-phosphate dehydrogenase deficiency D. Hereditary spherocytosis E. Hypersplenism F. Iron deficiency anaemia G. Megaloblastic anaemia H. Myelodysplastic syndrome I. Thalassaemia J. Thrombotic thrombocytopenic purpura What is the most likely diagnosis of the following investigation finding is present in an anaemic patient? Markedly hypocellular marrow

[Old PP] Patient with lowered haemoglobin level. Most important piece of information to determine clinical significance? A. Clinical diagnosis of the patient B. Reference interval of haemoglobin level C. Sex of the patient

[Old PP] What is the most likely diagnosis for a 40-year-old Cantonese man with the following blood picture? Hb: slightly low MCV: low MCH: low RDW: normal Reticulocyte: normal A. Aplastic anaemia B. Haemolytic anaemia C. Iron deficiency anaemia D. Thalassaemia major E. Thalassaemia trait

[Old PP] In which of the following conditions has application of exogenous erythropoietin proven useful? A. Anaemia due to alpha-thalassaemia B. Anaemia due to beta-thalassaemia C. Anaemia due to auto-antibodies D. Anaemia due to chronic renal failure E. Anaemia due to iron deficiency

[Old PP] A 43-year-old woman suffering from systemic lupus erythematosus (SLE) is admitted to the medical ward because of worsening dizziness and shortness of breath on exertion for 1 week. There has been no bleeding history. Her Hb is 7g/dL. White cell and platelet counts are normal. Exam of peripheral blood smear shows marked spherocytosis and polychromasia. Which of the following laboratory tests should be requested in order to understand the mechanism of her anaemia? A. Activated partial thromboplastin gene B. Direct antiglobulin test C. Haemoglobin pattern D. Osmolarity fragility E. Reticulocyte count

[PP] Diffuse lymphatic tissues, referred to as gut-associated lymphoid tissues (GALT), are distributed along the gastrointestinal tract. In which histological layer is GALT commonly found? A. Adventitia B. Mucosa C. Muscularis externa D. Serosa E. Submucosa

[PP] The secondary lymphatic organs maintain mature naive lymphocytes and initiate an adaptive immune response. Among the secondary lymphatic organs, which one has a cortex and medulla? A. Lymph nodes B. Spleen C. Thymus D. Tonsils

A Thymus (primary lymphatic organ): capsule, septa / trabeculae, cortex, medulla Lymph nodes (secondary lymphatic organ): capsule, trabeculae, superficial + deep cortex, medulla Spleen (secondary lymphatic organ): capsule, trabeculae, red & white pulps Tonsils: hemi-capsulated, follicles (~lymph nodes) in lamina propria & submucosa, X afferent lymphatic vessels

[PP] A 56-year-old man was diagnosed with lung cancer. He presented with shortness of breath 1 week after pulmonary resection and lymph node dissection. Chest CT showed a large free-flowing left-sided pulmonary effusion. Thoracentesis yielded 300mL of whitish-yellow fluid. What is the MOST LIKELY cause of the pleural effusion? A. Chylothorax B. Congestive heart failure C. Pleuritis D. Pulmonary embolism

A Thoracic duct (in mediastinum) delivers whitish chyle from cisterna chyli (confluence of lumbar & intestinal lymphatic trunks) to left venous angle (IJVs & subclavian veins merge to form brachiocephalic vein) Pulmonary resection may damage the thoracic duct

[PP] A 58-year-old man presents to the Accident and Emergency Department with abdominal pain and distension. He had an abdominal aortic aneurysm reconstruction one month ago. During the physical examination, a fluid wave test is positive for abdominal ascites and paracentesis returns milky fluid. Injury to which structure during the reconstruction is MOST LIKELY responsible for the ascites? A. Bronchomediastinal trunk B. Cisterna chyli C. Jugular trunk D. Right lymphatic trunk

[PP] What is the main function of germinal centre in superficial cortex in lymph nodes? A. Drainage of the lymph that enters the lymph node through the afferent lymphatic vessels B. Facilitation of the migration of T-lymphocytes from the blood into the lymph node C. Production of long-lived antibody-secreting plasma cells and memory B cells D. T cell maturation

C A: medullary sinuses B: Postcapillary high endothelial venules (HEV) D: thymus

[PP] Where do the T cells and B cells mature respectively?

T cells: thymus B cells: red bone marrow

[PP] Describe three histological features of lymphatic capillaries.

1. Blind-ended 2. Incomplete basement membrane 3. Loosely overlapped endothelial cells - lack of tight junctions 4. Anchoring filaments containing elastic fibres -> prevent the lumen from collapsing 5. Slightly larger in diameter than blood capillaries

[PP] Name the type of cells concentrically arranged in thymic (Hassall) corpuscles.

Type VI epithelioreticular cells

[PP] Describe the function of thymic (Hassall’s) corpuscles.

Degeneration centre (pink-stained in H&E): removal of apoptotic thymocytes

[PP] Name the predominant cell type in thymus.

Thymocytes / T lymphoblasts (maturing into immunocompetent T cells)

[PP] Name the major type of lymphocytes located in superficial and deep cortex of lymph node respectively.

Superficial cortex: B lymphocytes Deep cortex: T lymphocytes

[Self-assessment] Thalassaemia is a common genetic disease in Hong Kong. Which of the following best describes the abnormality in thalassaemia? A. Globin chains are structurally abnormal B. Globin chains are overproduced C. Globin chain production is imbalanced

C Alpha / beta-globin chains are structurally normal but reduced in quantity -> imbalance

[PP] The clinical spectrum of HbH disease varies from mild to severe anemia. How does the genetic defect in HbH disease cause anemia? A. Formation of alpha-4 B. Formation of beta-4 C. Formation of gamma-4

B HbH disease - 3 deletions of alpha-globin gene / 2 deletions + 1 non-deletional mutation - beta-4 formation - symptomatic: moderate - severe anaemia Hemoglobin Bart’s hydrops fetalis - alpha thalassaemia major - all 4 alpha-globin genes deleted - OR 3 deletions including severe non-deletional mutations (e.g. hemoglobin Constant Spring) - lethal intrauterine hemolytic anaemia

[Self-assessment] The severity of HbH disease varies greatly. Which of the following might ameliorate the severity of HbH disease? A. Persistent production of beta-globin B. Persistent production of zeta-globin C. Persistent production of gamma-globin

[Self-assessment] Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disease. The incidence of G6PD deficiency in Hong Kong males is 5%. Affected individuals may develop acute hemolytic anaemia when exposed to fava beans, certain drugs or severe infections. What is the expected incidence of G6PD deficiency in Hong Kong females? A. 0.25% B. 0.1% C. 0.5%

A q^2

[Self-assessment] Thalassaemias are inherited blood diseases caused by defects in globin genes. Which of the following statements concerning the genetic defects in beta thalassaemia is CORRECT? A. Beta thalassaemia is caused by the deletion of one or more alpha globin genes B. Beta thalassaemia is caused by point mutations in beta globin genes leading to reduced or no production of beta globin C. Beta thalassaemia is caused by unequal crossover between two sister chromatids

B Alpha thalassaemia - caused by unequal DNA crossover during meiosis - high homology of alpha globin genes (non-expressing pseudogenes look similar) => misaligned recombination between alpha 1,2 => de novo mutations (e.g. alpha-alpha-alpha anti3.7 duplications, -alpha3.7 deletions (common))

[Self-assessment] John has a homozygous mutation at his beta-globin gene. What is the expected frequency of his siblings carrying a mutant allele of beta-globin? A. 75% B. 50% C. 100%

[Self-assessment] A molecular chaperone named alpha hemoglobin stabilising protein (AHSP) binds free alpha globin reversibly. How might AHSP deficiency affect the severity of beta thalassaemia? A. AHSP deficiency exacerbates beta thalassaemia B. AHSP deficiency ameliorated beta thalassaemia C. AHSP deficiency does not affect the severity of beta thalassaemia

A alpha chaperone (AHSP) - reduce alpha-4 (very insoluble) precipitation - secondary target in addressing ineffective erythropoiesis

[Self-assessment] John has an intron 2-654 mutation at his beta-globin gene. Which of the following statements concerning his mutation is CORRECT? A. The mutation creates new splice sites causing a new exon to be incorporated B. The mutation locates in the promoter region to attenuate gene transcription C. The mutation destroys a normal splice sites causing to cause exon skipping

A Intron 2-654 (C->T) mutation - effect: beta-0 - second most common mutation in HK - mRNA with extra exon inserted between exon 2 & exon 3

[Self-assessment] Codon 41/42 mutation in beta globin gene is common among patients with beta thalassaemia in HK. How does this mutation affect beta globin expression? A. Beta globin mRNA is degraded B. Beta globin gene is silenced C. 0.5% beta globin protein is degraded

A Codon 41/42 mutation (△TCTT, -4, deletion, frameshift) - most common (40%) in HK - effect: beta-0 Nonsense-mediated mRNA decay (NMD)

[Self-assessment] Suppose that the frequency of a mutant allele affecting amino acid residues 41/42 of beta-globin in the HK population is 2%. What is the projected incidence of beta thalassaemia major caused by this mutation in HK? A. 0.04% B. 0.4% C. 0.01%

[Self-assessment] Why were JAK2 inhibitors tested for experimental treatment of beta thalassaemia? A. JAK2 exacerbates globin chain imbalance B. JAK2 exacerbates ineffective erythropoiesis C. JAK2 exacerbates iron overload

B Janus kinase 2 (JAK2) inhibition - address ineffective erythropoiesis - also for myeloproliferative disorders

[Self-assessment] What cells were used in gene therapy of beta-thalassaemia? A. white blood cells B. red blood cells C. haematopoietic stem cells

[Self-assessment] Why were hematopoietic stem cells (HSCs) used in gene therapy of beta thalassaemia? A. HSCs can proliferate B. HSCs can self renew and differentiate into red blood cells C. HSCs do not age or die

[PP] Beta-thalassaemia is mostly attributed to point mutations in beta-globin gene. Which of the following is MOST LIKELY used for the detection of multiple known point mutations? A. Amplification-refractory mutation system (ARMS) B. Gap-PCR C. Multiplex ligation-dependent probe amplification (MLPA) D. Restriction fragmention polymorphism (RFLP)

A Gap-PCR: large known deletions Multiplex ligation-dependent probe amplification: unknown deletions RFLP: one known point mutations

[PP] The clinical presentation of hemoglobin H disease varies greatly. Which of the following concurrent mutations might ameliorate the severity of hemoglobin H disease? A. A codon 41/42 mutation in one beta-globin gene B. An activating mutation in the promoter of one gamma-globin gene C. An inactivating mutation in one glucose-6-phosphate dehydrogenase gene D. An inactivating mutation in one hepcidin gene

[PP] A. Mildly increased production of beta-globin B. Mildly reduced production of beta-globin C. No production of beta-globin D. Production of haemoglobin C E. Production of haemoglobin D F. Production of haemoglobin E G. Reduced but detectable production of beta-globin H. Substantially increased production of beta-globin For each of the following mutations in beta-globin allele, match the corresponding impact on beta-globin production in the list of options above. Each option may be used once, more than once, or not at all. A->G at -28

G beta + (milder) -28 (A->G, TATA box i.e. promoter region) 4th most common in HK

C Codon 17 (A->T, nonsense) 5th most common in HK beta-0 * Nonsense mutation (TAG, TGA, TAA)

F E26K - missense mutation in Haemoglobin E thalassaemia - glutamic acid at position 26 -> lysine - structurally ABNORMAL haemoglobin, NOT reduced in quantity - 1 beta-globin gene carrying a thalassaemia mutation (mild / severe) + E26K mutation - prevalent in Southeast Asia (1 million hoz, 30 million hez)

[Self-assessment] Which of the following events occur during progenitor B (pro-B) cell differentiation in the bone marrow? A. Immunoglobulin gene rearrangement B. Surface expression of IgM molecules C. Cytoplasmic expression of light chains

A B: immature B cells C: pre-B cells

[Old PP] Explain the meaning of CD antigens.

CD = cluster designation / clusters of differentiation CD antigens - on leukocyte membranes - differentiation markers / lineage markers for lymphocytes - recognised by clusters of monoclonal antibodies E.g. CD19, 34, 40: lineage markers for B cells (targeted for B cell lymphoma)

[Self-assessment] During B cell development, the negative selection of autoreactive B cells occurs at which of the following B cell differentiation stages? A. Immature B B. Pro-B C. Pre-B

A B, C: no antigen receptor expression

[Old PP] Which CD antigens are used to monitor maturation of T cells in thymus and in what order do they appear?

CD3: all T cells, associated with TCR = lineage marker CD4: co-receptor for MHC-II on APCs, on helper T cells CD8: co-receptor for MHC-I on APCs, on cytotoxic T cells 1. On entering cortex: double-negative thymocytes (CD3- CD4- CD8-) 2. Cortico-medullary junction: double-positive thymocytes (CD3+ CD4+ CD8+) with TCR 3. Positive selection by presenting to self MHC (mostly thymic cortical epithelial cells) => mature, single-positive thymocytes (CD3+ CD4+ OR CD3+ CD8+)

[Old PP] Which of the following is a process occurring in developing B cells in bone marrow? A. Differentiation into mast cell B. IgA expressed on membrane surface C. IgE synthesis D. Heavy chain rearrangement E. Interferon-induced proliferation

[Old PP] In the development of B cells, the B cell receptors undergo various processes to generate diversity for antigen recognition. Which of the following is one of the processes? A. Somatic hypermutation B. Antigen binding at lymph nodes C. Rearrangement of immunoglobulin heavy chain gene D. Clonal expansion of B cells E. Class switching

C Somatic hypermutation -> affinity maturation Antigen binding -> trigger somatic hypermutation and clonal expansion Class switching -> greater immune response since IgG is more potent

[Old PP] T cell development takes place in the thymus. Which of the following is a correct sequence for T cell differentiation? A. CD4+ T cells differentiate into cytotoxic T cells B. CD4+ CD8+ T cells differentiate into CD4- CD8- (double-negative) T cells C. CD4+ CD8+ T cells mature into NK cells D. CD4- CD8- T cells differentiate into either CD4+ or CD8+ T cells E. CD8+ T cells mature into helper T cells

[Old PP] In the bone marrow, developing B cells A. Express IgD first on membrane surface B. Express IgM on pre-B cells C. Rearrange heavy chain at the immature B cell stage D. Require IL-10 to differentiate and proliferate E. Rearrange light chain before heavy chain

D Th1 subset: secrete IL-2, IFN Th2 subset: secrete IL-4, 5, 6, 10

[Old PP] A patient is diagnosed with the congenital disorder DiGeorge syndrome in which the thymus is absent. Which of the following would be true? A. Increased antibody production B. Increased lymphocyte levels C. Decreased NK cell levels D. Increased phagocytosis E. Effective innate immunity

[Old PP] Regarding T cell development in the thymus, A. CD4+ CD8+ cells differentiate into CD4- CD8- cells B. Most T cells express gamma-delta T cell receptors C. CD4- CD8- cells are located in thymic medulla D. Mature, functional T cells are either CD4+ CD8- or CD4- CD8+ cells E. Thymocytes undergo extensive immunoglobulin gene rearrangements

D B: should be alpha-beta TCR C: should be single-positive

[Old PP] Which of the following cellular mechanisms is involved in elimination of autoreactive T cells in thymus during negative selection? A. Anergy B. Apoptosis C. Necrosis D. Receptor editing E. Somatic hypermutation

B Anergy: negative selection of autoreactive B cells which encounter soluble self-antigen Receptor editing: further immunoglobulin light chain gene rearrangements => rescue potentially auto-reactive B cells

[Old PP] B cells are developed in bone marrow. Which of the following gives rise to different specificity of B cell receptors on mature B cells? A. Gene rearrangement of the heavy chain B. Antibody affinity maturation C. Class switching D. Somatic hypermutation

[PP] Name four components of haemostasis.

1. Blood vessels 2. Platelets 3. Coagulation factors 4. von Willebrand factor (vWF)

[PP] A 16-year-old boy suffered from knee pain and underwent a simple arthroscopic examination. Procedure was done without any intervention. However, after arthroscopy, the patient suffered from severe bleeding, with persistent bloody drainage from the wound drain. Red cell transfusion was needed. On further enquiry, there was no documented previous episode of abnormal bleeding. However, his elder brother died from intracranial haemorrhage at 8 years of age. CBC showed normal platelet count. The results of his coagulation studies are as follows: PT: 12.1s (Normal: 12.0-13.1s) APTT: 36.1s (Normal: 29.5-38.2s) TT: normal Fibrinogen: normal For this patient, what is the MOST LIKELY diagnosis?

Congenital factor XIII deficiency (not detected in routine test)

[PP] A 25-year-old woman was admitted to the acute medical ward for fever, gum bleeding and easy bruising for 1 week. On admission, complete blood count (CBC) showed: White blood cell count: decreased Absolute neutrophil count: decreased Hemoglobin: decreased Platelet count: decreased clotting profile showed: PT: prolonged APTT: prolonged Fibrinogen: decreased An urgent blood film review showed abundant circulating abnormal promyelocytes and faggot cells. Name the diagnosis.

Acute promyelocytic leukaemia

[PP] Outline three underlying mechanisms for the bleeding tendency observed in a patient with acute promyelocytic leukaemia (APL).

1. Disseminated intravascular coagulation (DIC) (due to activation of coagulation cascade by tissue factor and cancer procoagulant released from APL cells) 2. Myelosuppression by APL cells causing thrombocytopenia 3. Hyperfibrinolysis (due to activation of fibrinolysis by Annexin II on APL cells), hypofibrinogenaemia 4. Increase proteolysis by factors released from APL cells

[PP] Name the cytogenetic abnormality seen in acute promyelocytic leukaemia (APL).

t(15;17)(q24;q12) PML::RAR_alpha fusion

[PP] A 55-year-old man presented to the general medical ward with progressive shortness of breath, weight loss, generalised pruritis and left-sided abdominal discomfort for 6 months. Physical examination showed pallor and palpable splenomegaly at 20cm below the left costal margin along the Gardner’s line. Complete blood count (CBC) showed: White blood cell (WBC) count: increased Haemoglobin: decreased Platelet count: increased Peripheral blood film review showed a leucoerythroblastic blood picture with frequent tear-drop poikilocytes. Occasional circulating myeloblasts were observed. Name the MOST LIKELY underlying diagnosis.

Primary myelofibrosis (PMF)

[PP] Name the diagnostic investigation for primary myelofibrosis.

Bone marrow examination BMA: dry tap (severe marrow fibrosis) Trephine biopsy: streaming artefacts (severe marrow fibrosis stretch, elongated cells)

[PP] Name the COMMONEST genetic abnormality that may be found in primary myelofibrosis.

JAK2 V617F mutation

[PP] Name one pharmacological treatment that will alleviate the constitutional symptoms and splenomegaly in PMF.

Ruxolitinib (JAK/STAT inhibitor)

[PP] Name the curative treatment for primary myelofibrosis (PMF).

(Allogeneic) Haematopoietic Stem Cell Transplantation (HSCT)

[PP] Name one possible reason explaining the normal APTT in APL.

Factor VIII is acute phase reactant, level increases in acute onset => still “normal” APTT *Prolonged PT: due to short half-life of factor VII

[PP] Macrophage is one of the effector cells responsible for cell-mediated immunity against a variety of microorganisms through the effector mechanism of phagocytosis. Which of the following substances is produced by activated macrophages for killing and digesting the microorganisms inside the phagosomes? A. IFN-gamma B. IgG C. Lysozyme D. Perforin

C IFN-gamma: T, NK cells Perforin: Cytotoxic T cells, NK cells

[PP] CD8+ cytotoxic T lymphocytes are one of the effector cells responsible for cell-mediated immunity against virus infection through the killing of virus infected cells. In such killing processes, perforin and granzymes are released from the activated cytotoxic T lymphocytes cells. Which of the following does perforin serve for this immune defense? A. Binding to MHC class I molecules B. Forming pores in the target cell membrane C. Induction of apoptosis in target cell D. Recognising viral antigen

B Perforin: form pores in cell membrane -> osmotic lysis + allow granzymes to enter Granzymes: -> activate apoptosis -> sometimes toxic to intracellular pathogens (e.g. granulysin) Fas ligand (bind to Fas on target cell) -> activate caspase & endonuclease => apoptosis

[PP] Virus infected cells that activate CD8+ cytotoxic T cells must express which of the following on their surfaces? A. CD28 B. CD80/86 C. Viral antigen presented through MHC class I molecules D. Viral antigen presented through MHC class II molecules

[PP] Which of the following mechanisms is involved in phagocytosis? A. Antibody neutralisation B. Antibody isotype switching C. Cell degranulation D. Complement opsonisation E. Perforin activation

D 3 mechanisms of phagocytosis recognition: 1. Fc receptor-mediated 2. Complement receptor-mediated (complement deposited on pathogens via alternative / classical / lectin-induced pathway) (e.g. C3b, C3bi, C1q receptor on macrophages) 3. Mannose receptor mediated (oligosaccharide on pathogens)

[PP] Which two types of cells are targeted by the secretion of cytokines?

1. Macrophages 2. Lymphocytes (e.g. induce B cell isotype change to become those that can involve in ADCC)

[PP] Macrophages interact with T helper cells to trigger the secretion of cytokines from the latter which act in a paracrine fashion. How do macrophages interact with T helper cells? (3 marks)

1. Antigen presentation Macrophages present peptides on MHC class II molecules, binding to T cell receptors (TCR) on T helper cells 2. CD40 on macrophage binds to CD40L on T helper cells => macrophage activation CD80/86 on macrophage binds to CD28 on T helper cells 3. Cytokine interaction T helper cells release IFN-gamma which activate macrophages to enhance phagocytosis Macrophages release IL-12 to stimulate T helper cells

[PP] Tuberculosis can be controlled by specific T cell responses against Mycobacterium tuberculosis. Which cell type is critical for activating naive T cells to mount specific cellular responses against Mycobacterium? A. B cells B. Dendritic cells C. Mast cells D. Natural killer cells E. Respiratory epithelial cells

B As APCs

[Workshop] What are the immediate management measures in a patient with suspected acute promyelocytic leukaemia (APL)?

1. Initiation of ATRA/ATO 2. Correction of haemostatic problems (coagulopathy, thrombocytopenia): platelet transfusion and transfusion of fibrinogen concentrate/cryoprecipitate/fresh frozen plasma (3. Treat any infection 4. Prevent tumour lysis syndrome)

[Workshop] What are the differences in peripheral blood features between primary myelofibrosis (PMF) and chronic myeloid leukaemia (CML)?

PMF - leucoerythroblastic blood picture with tear-drop poikilocytes CML - bimodal prominence of myelocytes and neutrophils, basophilia

[Self-assessment] One IgM molecule consists of the following structure components: A. Two antigen-binding sites B. Two variable regions C. Two constant regions

[Self-assessment] Which of the following isotypic antibodies involved in allergic reactions? A. IgD B. IgA C. IgE

C IgA - mucosal immunity - in external seromucous secretions (saliva, breast milk, tears, colostrums, tracheobronchial & genitourinary secretions) IgD - antigen-triggered lymphocyte differentiation - enhance basophils IgE - immediate hypersensitivity / allergy (hay fever, asthma, hives, - immunity of helminthic parasites

[Self-assessment] Viral infected cells that activate CD8+ cytotoxic T cells must express which one of the following on their surfaces? A. Viral antigen presented through MHC class II molecules B. Viral antigen presented through MHC class I molecules C. Killer activatory receptors

B Killer activatory receptor (NK): - lectin recognises any carbohydrate on cell -> release cytotoxic factors Killer inhibitory receptor (NK): - Ly49 binds to self MHC-1 -> prevent release of cytotoxic granules

[Workshop] What is pathophysiologic mechanism of TTP? A. Deficiency of von Willebrand factor B. Deficiency of ADAMTS13 C. Increased Factor VIII D. Increased Tissue Factor

[ALW] A patient presented with aPTT prolongation, but did not exhibit any bleeding disorder. Which clotting factor deficiency could have produced this phenomenon? A. Factor X B. Factor VIII C. Factor V D. Factor XII

D Deficiency of contact factors (factor XII, prekallikrein, high molecular weight kininogen HMWK) -> prolong APTT - No bleeding tendency - Initiate intrinsic pathway in lab tests - No major physiological role in haemostasis - Common polymorphism in Orientals Factor V, X: common pathway Factor VIII: intrinsic pathway

[ALW] In the diagnosis of Classical Hodgkin lymphoma, which of the following features is diagnostic? A. Presence of plasma cells B. Presence of B cells C. Presence of T cells D. Presence of Reed-Sternberg cells

D Hallmark of cHL = Hodgkin Reed-Sternberg (HRS) cells

[ALW] For an individual with factor V deficiency, how would their PT and APTT be affected? A. APTT prolonged B. PT prolonged C. APTT and PT prolonged D. APTT and PT normal

C Common pathway

[ALW] In the evaluation of isolated prolongation of activated partial thromboplastin time (APTT), what are the objectives of performing a 1:1 mixing study? A. To look for von Willebrand factor deficiency B. To detect the presence of autoantibodies in the serum C. To differentiate between clotting factor deficiency versus the presence of a clotting factor inhibitor D. To look for clotting factor deficiency only

C 1:1 mix of patient plasma & normal plasma at 37°C for 1h

[ALW] In patients with isolated prolongation of APTT, which of the following is associated with bleeding? A. Factor IX deficiency B. Presence of lupus anticoagulant C. Heparin contamination D. Factor XII deficiency

[Self-assessment] A 12-year-old girl presented with menorrhagia. She also had history of easy bruising, epistaxis. On physical examination, she had pallor. Otherwise the physical examination findings are unremarkable. Ultrasound pelvis is unremarkable. Complete blood count: Hb - lowered WBC, platelet count - normal PT - normal APTT - elevated What is the most possible diagnosis in this patient? A. Immune thrombocytopaenia purpura B. Congenital haemophilia A C. Von Willebrand disease

C Mucocutaneous bleed -> platelet / vessel / vWF defect Mildly prolonged APTT: reduced factor VIII due to vWD (may be normal) Congenital haemophilia A: - X-linked recessive => less likely in females

[Self-assessment] A 52-year-old woman admitted for pyelonephritis. She developed septic shock despite receiving broad spectrum antibiotics and warranted ICU care. Her platelet count was 34 only (ref: 162-390*10^9/L) and thus ICU colleagues consulted haematologists for review. PT: elevated APTT: normal Peripheral blood smear showed genuine thrombocytopenia with occasional giant platelets present. Neutrophilia with toxic changes. Left shift also seen with the presence of occasional myelocytes and metamyelocytes in peripheral blood. What is the haematological condition that most likely can explain the thrombocytopaenia in this patient? A. Thrombotic thrombocytopenic purpura B. Disseminated intravascular coagulation C. Immune thrombocytopenic purpura

B Sepsis, prolonged PT TTP: absence of features of microangiopathic haemolytic anaemia (e.g. schistocytes / red cell fragments)

[Self-assessment] Why is the APTT normal in a patient with disseminated intravascular coagulation? A. Elevated factor VII B. Elevated factor VIII C. Laboratory error

B Factor VIII is an acute phase reactant, level increases in acute onset

[PP] A. Acquired haemophilia A B. Coagulopathy due to liver failure C. Congenital factor VII deficiency D. Congenital factor XIII deficiency E. Congenital haemophilia A F. Contact factor deficiency G. Heparin contamination during blood taking H. Idiopathic thrombocytopenic purpura I. Superwarfarin poisoning J. von Willebrand disease A 28-year-old female with good past health presented with easy bruising, epistaxis and menorrhagia. Platelet count, PT and APTT as well as TT, fibrinogen were all normal. What is the most relevant diagnosis?

J Mucocutaneous bleed -> platelet / vessel / vWF defect

[PP] A. Acquired haemophilia A B. Coagulopathy due to liver failure C. Congenital factor VII deficiency D. Congenital factor XIII deficiency E. Congenital haemophilia A F. Contact factor deficiency G. Heparin contamination during blood taking H. Idiopathic thrombocytopenic purpura I. Superwarfarin poisoning J. von Willebrand disease A 78-year-old woman had an appendectomy in the past with uneventful recovery. She presented with large muscle haematoma and haemarthrosis. There was no previous history of bleeding episodes. Platelet - normal PT - normal APTT - markedly elevated TT, fibrinogen - normal What is the most relevant diagnosis?

A Deep-seated bleeding -> coagulation factors / severe vWF defect Isolated prolonged APTT -> defect of intrinsic pathway Bleeding tendency -> X factor XII Elderly -> acquired

[PP] A. Acquired haemophilia A B. Coagulopathy due to liver failure C. Congenital factor VII deficiency D. Congenital factor XIII deficiency E. Congenital haemophilia A F. Contact factor deficiency G. Heparin contamination during blood taking H. Idiopathic thrombocytopenic purpura I. Superwarfarin poisoning J. von Willebrand disease A 2-year-old boy presented with haemarthrosis. Platelet - normal PT - normal APTT - markedly elevated TT, fibrinogen - normal What is the most relevant diagnosis?

E Deep-seated bleeding -> coagulation factors / severe vWF defect Isolated prolonged APTT -> defect of intrinsic pathway Bleeding tendency -> X factor XII defect Early childhood -> congenital

[PP] A 68-year-old man had a history of spine surgery with uneventful post-op recovery. He presented with dizziness. Physical examination did not find any signs of bleeding tendency. Platelet - normal PT - normal APTT - markedly elevated TT, fibrinogen - normal What is the most relevant diagnosis?

F Isolated prolonged APTT -> defect of intrinsic pathway No bleeding tendency -> factor XII OR contact factor (prekallikrein, HMWK) deficiencies

[Old PP] What coagulation factors require vitamin K for post-translational modifications?

Factor II (prothrombin), VII, IX, X

[Old PP] A previously healthy patient developed deep vein thrombosis 6 weeks ago. Patient fell and caused left calf swelling. Complete blood count and peripheral blood smear are normal. INR = 7.0 What is the cause of abnormal coagulation?

Overdose of warfarin (anticoagulant, vitamin K antagonist) => abnormally high INR INR = (PT_test/PT_standard)^ISI - for warfarin titration ONLY - NOT direct oral anticoagulants / DIC

[PP] Mary, 25-year-old, received three doses of human papillomavirus (HPV) vaccine in her teenage. She learnt from internet sources that HPV vaccine could induce T cell immunity for protection against cervical cancer. Her elder sister never had any HPV vaccination and was recently diagnosed with cervical cancer. For effective vaccination protection, more than 1 dose of vaccine is recommended. Give one immunological explanation for this recommendation.

To generate high affinity antibodies to neutralise / remove the pathogens (affinity maturation) OR To generate long lasting specific cellular responses to the pathogens by increasing the frequency of memory T/B cells

[PP] Can the transfer of T cells from Mary to her sister be a possible anticancer treatment option? (1 mark) Explain your answer with the key immunological concepts involved. (3 marks)

No (1 mark) Antigen-specific T cell response is restricted by MHC molecules (1 mark): T cells recognise antigens presented by self-MHC to mediate immune reactions MHC in human (or HLA) is highly polymorphic, the sisters are not likely to have identical HLA (1 mark): Mary’s T cells cannot recognise antigens presented by MHC of her sister’s cells Mary sister’s immune system recognises the alloantigens on Mary’s T cells and causes rejection (1 mark)

[Self-assessment] Matching of which of the following is considered important for performance of haematopoietic stem cell transplant? A. Gender B. Rhesus blood group C. ABO blood group D. Human Leukocyte Antigen

[Old PP] Ruby is a 16-year-old student who had leukaemia 3 years ago. Despite treatment by bone marrow transplantation, her leukaemia has recently recurred. Besides leukaemia treatment, she is taking anti-infection medications because of increased risks of multiple infections. What is the terminology used to describe infections in high risk patients such as Ruby, and how are they defined?

Opportunistic infections Infections caused by pathogens which do not normally infect healthy hosts, but instead infect inmunocompromised / immunosuppressed hosts

[Old PP] Ruby is a 16-year-old student who had leukaemia 3 years ago. Despite treatment by bone marrow transplantation, her leukaemia has recently recurred. Besides leukaemia treatment, she is taking anti-infection medications because of increased risks of multiple infections. List three common organisms that cause this type of infection.

Candida albicans / Pneumocystis jirovecii / Pseudomonas aeruginosa

[Old PP] Ruby is a 16-year-old student who had leukaemia 3 years ago. Despite treatment by bone marrow transplantation, her leukaemia has recently recurred. Besides leukaemia treatment, she is taking anti-infection medications because of increased risks of multiple infections. List two possible reasons why Ruby has increased risk of infections.

1. Leukaemia -> immature & dysfunctional WBCs, (thrombocytopenia -> slow blood clotting and wound healing -> exposure of wounds to pathogens) -> immunosuppression 2. Immunosuppressive drugs to prevent post-transplant rejection, (chemotherapy, radiotherapy)

[Old PP] A 4-year-old boy who underwent liver transplantation 3 months ago presents with deranged liver function at the follow-up clinic. Liver biopsy shows acute rejection. What is the main cell type responsible for this process? A. B lymphocytes B. Mast cells C. Natural killer cells D. Neutrophils E. T lymphocytes

[Old PP] Which of the following is TRUE in clinical haematopoietic stem cell transplantation? A. Gender compatibility is desirable B. MHC compatibility is needed C. Non-malignant disease can also be treated D. Parents are the ideal donors E. The marrow is the only source of haematopoietic stem cells

B, C MHC compatibility is required by HLA matching (at least 5/6) Non-malignant disease, e.g. SCID Parents: only 3/6 (half-matched / haploidentical) Sources of HSCs: BM / peripheral blood / umbilical cord blood

[Old PP] 2-year-old girl admitted to hospital with deranged liver function, the medical history revealed that she has liver cirrhosis and had a liver transplant eight months ago. She was found to have higher than normal level of tacrolimus and high titre of EBV in blood. What is the diagnosis? A. Acute organ rejection B. Drug-induced hepatotoxicity C. Hepatocellular carcinoma D. Opportunistic viral infection E. Hepatic artery thrombosis

D Acute organ rejection: acute graft-versus-host disease (GVHD)

[Old PP] Which of the following is TRUE is bone marrow transplantation? A. A suitable donor is a necessity in bone marrow transplantation B. Bone marrow transplantation is the treatment of choice for acute leukaemia C. In bone marrow transplantation for malignancies, a source of marrow not contaminated by tumour cells is needed D. Pancytopenia develops in about 60% of patients in the first four weeks after bone marrow transplantation E. Recovery of immune function occurs with engraftment, which is about 4 weeks after bone marrow transplantation

C A: can be autologous B: should be chemotherapy D: should be nearly 100% after bone marrow ablation (conditioning therapy) and before engraftment E: recovery takes months to years

[Old PP] Many types of cells in the immune system and mechanisms are involved in the initiation of allograft rejection in organ transplantation. Which statement about the function of these cells is NOT true? A. Direct presentation or recognition of transplantation antigen (i.e. MHC molecules) by dendritic cells is supposed to be a cross-reaction of a normal T cell receptor (TCR), which is selected to recognise a self-MHC molecules plus foreign antigen, with an allogeneic MHC molecule plus peptide B. Hyperacute rejection (rejection occurs within hours after organ transplantation) usually is mediated by cytotoxic T lymphocytes but not natural antibodies C. In acute rejection, CD8+ T lymphocytes reacting with alloantigens on endothelial cells and parenchymal cells mediate damage to these cell types D. In chronic rejection with graft arteriosclerosis, injury to the vessel wall leads to intimal smooth muscle cell proliferation and luminal occlusion, which may be induced by a chronic delayed-type hypersensitivity (DTH) reaction to alloantigens in the vessel wall E. The most critical barriers in current experimental xenograft transplantation is how to overcome the hyperacute rejection

B Hyperacute rejection: - natural antibodies (e.g. against ABO or HLA antigens) activate complement system -> graft destruction Chronic rejection: - DTH => chronic inflammation and fibrosis of vessel Xenotransplantation - Barrier: preformed natural antibodies against non-human antigens

[PP] A 30-year-old man presented with progressive weight loss, night sweats and generalised pruritis for 4 weeks. Physical examination showed a 3cm palpable lymph node over the left supraclavicular fossa that was rubbery in nature. An excisional biopsy of the lymph node was performed. The histology showed distortion of nodal architecture. Large and multinucleated abnormal lymphoid cells were present. The abnormal lymphoid cells were surrounded by normal lymphocytes, plasma cells and eosinophils. What is the MOST LIKELY diagnosis? A. Classical Hodgkin lymphoma B. Diffuse large B-cell lymphoma C. Follicular lymphoma D. NK/T-cell lymphoma

A Fever, night sweats, weight loss, respiratory symptoms (e.g. dry cough) Multinucleated Reed-Sternberg cells Eosinophilia

[PP] A 40-year-old man with Hodgkin lymphoma is treated with a combination of doxorubicin, cyclophosphamide and vincristine. Which baseline investigation should be ordered before treatment is commenced? A. Echocardiography B. Pulmonary function test C. Exercise stress test D. Urinalysis

A Doxorubicin (Hydroxyl-daunorubicin) - anthracycline (topoisomerase II blocker) - cardiotoxicity

[PP] A 62-year-old man presents with a white cell count of 21*10^9/L. Differential count shows 85% of the white cells to be small lymphocytes. What is the MOST LIKELY diagnosis? A. Acute viral infection B. Chronic lymphocytic leukaemia C. Disseminated malignant lymphoma D. Infectious mononucleosis E. Pulmonary tuberculosis

B CLL (including SLL variant) often diagnosed with incidental findings CLL -> >5*10^8 clonal B cells in circulation (leukocytosis) This is probably SLL (small lymphocytic lymphoma)

[PP] A 56-year-old man was newly diagnosed to have mantle cell lymphoma, a mature B-cell lymphoma. Further genetic test showed that the patient carried oncogenic aberrations of t(11;14)(q13;q32). Where did the oncogenic mutation of this patient arise from? A. Common myeloid progenitors B. Haematopoietic stem cell C. Mature B lymphocytes D. Precursor B cells

C MCL: from mantle zone of lymphoid follicles (mature, naive B cells) Precursor B cells: in bone marrow

[PP] An 80-year-old woman with good past health presented with progressive dyspnoea on exertion for 3 months. The complete blood count (CBC) showed; WBC - lowered Hb - lowered MCV - elevated Platelet count - lowered The peripheral blood film showed absent polychromasia. In addition, macrocytes, hypolobated and hypogranular neutrophils were observed. What is the MOST LIKELY diagnosis? A. Acute myeloid leukaemia B. Haemolytic anaemia C. Myelodysplastic syndrome D. Pernicious anaemia

[PP] A 42-year-old woman was admitted for abdominal pain. Peripheral blood smear showed features consistent with chronic myeloid leukaemia (CML). Bone marrow examination and cytogenetic study confirmed the diagnosis. What is the pathological mechanism of CML? A. Loss of chromosome 7 in common myeloid progenitors B. Loss of long arm of chromosome 5 in common myeloid progenitors C. t(9;22) in the haematopoietic stem cell D. t(9;22) in the precursor B-cell

C Low grade MDS: del(5q), monosomy 7 CML: t(9;22): Philadelphia chromosome (BCR::ABL1 fusion)

[PP] A 30-year-old woman was found to have microcytosis. Haemoglobin pattern study showed features consistent with alpha thalassaemia trait. Globin phenotypic was performed and confirmed that she carries heterozygous two alpha genes deletion of SEA type. Now she got married and pregnant at 8 weeks of gestation. Her husband showed normal results of haemoglobin pattern study. He is suspected to be silent carrier of alpha gene aberrations. Globin genotyping is performed on her husband to exclude this possibility. Which of the following is the BEST strategy for the molecular diagnosis of the husband? A. Amplification refractory mutation system only B. Gap-PCR and Sanger sequencing C. Multiplex Ligation-dependent Probe Amplification only D. Sanger sequencing only

[PP] A 49-year-old man was admitted for prolonged bleeding after tooth extraction 1 week ago. Complete blood count on admission showed: Haemoglobin - lowered White blood cell count - elevated Platelet count - lowered Absolute neutrophil count - lowered Clotting profile showed: Prothrombin time - elevated APTT - normal Fibrinogen - lowered Peripheral blood film showed 91% abnormal promyelocytes. What is the MOST LIKELY underlying genetic abnormality? A. BCR::ABL1 gene fusion B. CALR mutation C. JAK2 V617F mutation D. PML::RARA gene fusion

[PP] A 68-year-old man presented with malaise and weight loss. On physical examination, he was afebrile, with cervical lymphadenopathy. A complete blood count has been performed, which showed: Haemoglobin - lowered White blood cell - elevated Platelet - lowered Peripheral blood smear showed lymphocytosis, with the presence of circulating abnormal (malignant) lymphoid cells. Suggest a possible diagnosis.

Chronic lymphocytic leukaemia (CLL) / Small lymphocytic lymphoma (SLL)

[PP] A bone marrow specimen was collected for evaluation of a patient with suspected CLL/SLL. List two methods for immunophenotyping of the abnormal lymphoid cells.

1. Flow cytometry 2. Immunohistochemistry

[PP] List one advantage and one disadvantage of each of the two immunophenotypic methods.

1. Flow cytometry -> Advantage: can investigate co-expression of antigens on a single cell -> Disadvantage: performed on peripheral blood or marrow aspirate, bone marrow architecture not preserved compared to trephine biopsy OR requires specialised equipment and expertise, and the staining procedure can be time-consuming 2. Immunohistochemistry -> Advantage: performed on trephine biopsy, with preserved bone marrow architecture -> Disadvantage: difficult to demonstrate co-expression of antigens on a single cell

[PP] A 25-year-old man with good past health presented with neck lumps of increasing size for 3 months. He was otherwise asymptomatic and had not taken any medication. On physical examination, there was no fever, but there were multiple cervical lymph nodes with rubbery to firm consistency. Complete blood count showed: Haemoglobin level: normal White cell count: elevated Platelet count: normal Absolute eosinophil count: elevated Peripheral blood smear shows mild leukocytosis, with eosinophilia. There are no circulating abnormal lymphoid cells. Which of the following investigations is the MOST APPROPRIATE at this juncture? A. Bone marrow examination B. Conventional karyotyping C. Fluorescence in-situ hybridisation D. Lymph node biopsy E. Stool for ova and cyst

[PP] What haematopoietic abnormality is present in myelodysplastic syndrome? A. Abnormality in a common myeloid progenitor cell which shows ineffective maturation B. Abnormality in a granulocytic progenitor cell which blocks maturation C. Abnormality in a haematopoietic stem cell which permits effective maturation D. Abnormality in a mature B cell in the lymph node which maintains the maturation state E. Abnormality in a pre-T progenitor cell which blocks maturation

[PP] A 56-year-old man presented with abdominal pain. Physical examination showed splenomegaly of 17cm below costal margin. Complete blood count showed: Hb - lowered White cell count - elevated Platelet - elevated Peripheral blood smear showed leukocytosis with bimodal distribution of myelocytes and neutrophils, basophilia and some giant platelets. Which of the following investigational results is MOST LIKELY in this clinical scenario? A. Bone marrow aspirate shows a hypercellular marrow with the presence of dysplastic features in all haematopoietic lineages B. Conventional karyotyping shows monosomy 7 as the sole karyotypic abnormality C. Fluorescence in-situ hybridisation shows positive signals for BCR-ABL1 rearrangement D. Molecular study shows positivity for JAK2 V617F mutation

C Chronic myeloid leukaemia (MPN) A: MDS B: MDS (del(5q), monosomy 7)

[PP] A 72-year-old man had a history of lung cancer and presented with dizziness. Physical examination showed pallor and no organomegaly. A complete blood count showed the following: Hb - lowered White blood cell - lowered Platelet - lowered Peripheral blood smear showed leukopenia and neutropenia, with occasional circulating blasts and presence of dysplastic features in neutrophils. Which of the following investigational features is MOST PROBABLE in this clinical scenario? A. Bone marrow aspirate shows the presence of abnormal promyelocytes B. Conventional karyotyping show monosomy 7 as the sole karyotypic abnormality C. Fluorescence in-situ hybridisation shows positive signals for BCR-ABL1 rearrangement D. Molecular study shows positivity for JAK2 V617F mutation

[PP] A 50-year-old man completed an orthopaedic surgery yesterday. This morning he complained of swelling in his left leg and difficulty in breathing. Blood flow obstruction was found in his left leg and lungs later. What is the MOST PROBABLE pathological cause?

Venous thromboembolism

[PP] An oncogenic mutation occurring in the common myeloid progenitors causes differentiation arrest. Which haematological disease does this genetic lesion give rise to? A. Acute lymphoblastic leukaemia B. Acute myeloid leukaemia C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia

[PP] Stem cells have many unique properties compared to other somatic cells. What is the property of haematopoietic stem cells that allows them to sustain haematopoiesis throughout a person’s life? A. Dormancy B. Multilineage differentiation potential C. Plasticity D. Self-renewal E. Tightly regulated signalling to haematopoietic stem cells

[PP] What is the major function of cortex in thymus?

T cell maturation by positive selection of immature T cells -> recognise antigens Medulla: T cell education by negative selection -> prevent over-reaction and autoimmunity

[PP] What is the major cell type in cortex of thymus?

T lymphocytes

[PP] Name the lymphatic duct that drains the lymph from coeliac lymph node into the blood.

Thoracic duct Lymphatic trunk: intestinal trunk

[PP] Name the vascular structure that delivers lymphocytes into the lymph node.

High endothelial venules (HEV) / capillaries

[Old PP] For malignant lymphoma, explain in no more than five words the use of positron emission tomography.

Staging (lymphadenopathy, distant metastasis, hepatosplenomegaly)

[Old PP] For malignant lymphoma, explain the use of immunophenotyping.

Determine cell lineage by detecting antigens on the cells-of-interest

[Old PP] For malignant lymphoma, explain the use of bone marrow trephine biopsy.

Staging (examine BM architecture, check for any BM involvement), allow immunohistochemistry

[Old PP] For malignant lymphoma, explain the use of fluorescence in-situ hybridisation.

Detect chromosomal abnormalities (fusion genes, copy number variation)

[Old PP] for malignant lymphoma, explain the use of gene rearrangement study.

Confirm cell lineage, predict prognosis

[Old PP] What is the main treatment modality for a patient with B cell lymphoma?

Chemotherapy e.g. R-CHOP Rituximab Cyclophosphamide Hydroxydaunorubicin (doxorubicin / adriamycin) Oncovin (vincristine) Prednisone (inactive) / Prednisolone (active)

[Old PP] A 60-year-old presents with weight loss and fever for two months. Physical examination shows generalised lymphadenopathy 3-4cm in size. Investigations: Hb: 11.0g/L (11.00-15.00g/dL) White cell count: 10*10^9/L (4-11*10^9/L) Differential count: normal Platelet count: 160*10^9/L (150-450*10^9/L) LDH: 2000IU/L (105-333IU/L) Bone marrow biopsy: Abnormal lymphoid infiltrate in bone marrow Name two essential investigations for this patient.

1. Excisional biopsy of lymph node 2. Immunophenotyping of bone marrow trephine biopsy

B cell lymphoma infiltrating bone marrow (nodal lymphoma is most likely B cell lymphoma in which peripheral blood has no quantitative or qualitative abnormalities) Fever, weight loss, night sweats

Ann Arbor Stage IV Bone marrow involvement High LDH: high tumour load & proliferative potential, may have liver metastasis Ann Arbor staging: - Stage 1: single lymph node / extranodal site - Stage 2; 2+ LNs / sites (SAME side of diaphragm) - Stage 3: Both sides (may include spleen) - Stage 4: Diffuse extralymphatic involvement (e.g. liver, BM, lung, skin)

[PP] A patient with atrial fibrillation has used warfarin for many years for prevention of thrombosis. His doctor would like to change his warfarin to dabigatran. What is the mechanism of action of warfarin, dabigatran and apixaban respectively?

1. Warfarin - inhibit clotting factor synthesis [structural analogue of vit. K => inhibit vit. K epoxide reductase => inhibit post-translational carboxylation of factor II, VII, IX, X and protein C => reduce synthesis of active clotting factors] 2. Dabigatran - direct thrombin inhibitor => inhibit fibrin production 3. Apixaban - direct factor Xa inhibitor => inhibit common pathway of clotting cascade

[PP] List two advantages of dabigatran over warfarin.

1. Does not have the problem of food-drug interaction 2. Drug monitoring is not required (3. Less bleeding 4. Lower risk of drug-drug interactions)

[PP] A 65-year-old man suffering from acute myocardial infarction is brought to the Emergency Department. What drug is the BEST choice to improve blood flow to the ischaemic region of the heart if percutaneous coronary intervention is not immediately available?

Thrombolytic drug

[PP] What is the mechanism of action of thrombolytic drug?

It activates the conversion of plasminogen to plasmin, which breaks down fibrin and lyses the thrombi

[PP] Leucovorin is used in combination with other chemotherapeutic drugs to either enhance the effectiveness (e.g. fluorouracil) or as a chemoprotectant (e.g. methotrexate). Explain the respective mechanisms for leucovorin’s actions in chemotherapy.

1. Leucovorin is a reduced folic acid. It is not cytotoxic itself, but it enhances the binding of fluorouracil to thymidylate synthetase to inhibit DNA synthesis - 5-FU (pyrimidine antagonist) converts to FdUMP -> inhibit thymidylate synthase (TMS) -> block formation of normal pyrimidine nucleotides -> inhibit DNA synthesis - 5-FU -> 5FUTP -> incorporated into RNA -> induce cell death 2. When used together with methotrexate (MTX), leucovorin provides a source of folic acid for the normal cells thus preventing or alleviating the side effects - Leucovorin = active form of folate, bypass dihydrofolate reductase -> reduce MTX toxicity - MTX (folate antagonist / antifolate): occupy active site of dihydrofolate reductase -> reduced availability of co-enzymes for methylation of purines, thymidine, and amino acids (methionine, serine)

[PP] Bleeding is a common adverse effect of antiplatelet agents, anticoagulants and thrombolytic agents. Tranexamic acid is useful to treat the bleeding problem caused by these agents. What is the mechanism of action of tranexamic acid? A. Activation of thrombin B. Activation of vitamin K epoxide reductase C. Enhancing the interaction between antithrombin and coagulation factors D. Increasing the sensitivity of glycoprotein IIb/IIIa receptors E. Inhibition of plasminogen activation

E Reversal of bleeding problems caused by thrombolytic drugs

[PP] Dabigatran is an anticoagulant used for stroke prevention in atrial fibrillation and the prevention and treatment of venous thromboembolism. Which coagulation factor is inhibited by dabigatran? A. Factor II B. Factor IX C. Factor X D. Factor XI E. Factor XII

A Direct thrombin inhibitors - Oral: dabigatran - Parenteral: hirudin (leech saliva), lepirudin (synthetic hirudin), argatroban (completely different from hirudin)

[PP] Antimetabolites, including folic acid, pyrimidine or purine analogues, are effective chemotherapeutic agents for cancer patients. These induce cell death when incorporated into RNA and DNA, or inhibit enzymes responsible for nucleic acid production. In order to prevent toxicity towards normal cells, which of the following drugs is used in combination with methotrexate for cancer treatment? A. Dexrazoxane B. Glucocorticoid C. Leucovorin D. Thalidomide

[PP] In antigen-presenting cell (APC)-T cell interactions, co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) on APC bind to CD28 on T cells to deliver activation signals. Which of the following molecules is induced to expressed on activated T cells which bind to B7 molecules with a much higher affinity and deliver inhibitory signals? A. CD4 B. CD8 C. CD40 D. CTLA-4 E. ICAM-1

D CTLA-4: cytotoxic T lymphocyte antigen-4 Immune checkpoint

[PP] A 45-year-old man received a renal transplant one month ago and is being maintained on immunosuppressant drugs. Which combination of immunosuppressive drugs should be avoided? A. Tacrolimus, basiliximab and prednisone B. Tacrolimus, cyclosporine and prednisone C. Tacrolimus, mycophenolate mofetil and prednisone D. Tacrolimus, sirolimus and prednisone

B Tacrolimus, cyclosporine: inhibitor of calcineurin phosphatase (same MOA & metabolic route) Given together => additive nephrotoxicity

[PP] A 35-year-old female patient has just received a liver transplantation and is taking immunosuppressants. Which of the following immunosuppressive agents specifically inhibits calcineurin in the activated T-lymphocytes? A. Basiliximab B. Mycophenolate mofetil C. Sirolimus D. Tacrolimus

D Basiliximab: IL-2 receptor antagonist / Anti-CD25 antibodies Mycophenolate mofetil: antimetabolite Sirolimus: mTOR inhibitor

[PP] A 3-year-old girl with a history of allogeneic bone marrow transplantation has been admitted with fever, diarrhoea and generalised skin rash. A clinical diagnosis of graft versus host disease is made. What is the recommended first-line treatment? A. Cisplatin B. Corticosteroids C. Intravenous immunoglobulins D. Plasmapheresis

[PP] A 45-year-old man received a renal transplant one month ago and is being maintained on immunosuppressant drugs. Which immunosuppressive drug should be avoided, apart from tacrolimus and prednisone? A. Basiliximab B. Belatacept C. Cyclosporine D. Mycophenolate mofetil E. Sirolimus

C Basiliximab: IL-2 receptor antagonist / Anti-CD25 antibodies Belatacept: costimulation blocker Cyclosporine: calcineurin inhibitor Mycophenolate mofetil: antimetabolite Sirolimus: mTOR inhibitor

[Old PP] A. Acetylsalicylic acid / aspirin B. Antithrombin III C. Heparin D. Dabigatran E. Vitamin K F. Fibrinogen G. Tranexamic acid H. Thrombin I. Clopidogrel J. Warfarin Select the most suitable anti-coagulant for the following. Patient Mrs. Wong has atrial fibrillation. The doctor prescribes a drug by IV to prevent further thrombus formation.

[Old PP] A. Acetylsalicylic acid / aspirin B. Antithrombin III C. Heparin D. Dabigatran E. Vitamin K F. Fibrinogen G. Tranexamic acid H. Thrombin I. Clopidogrel J. Warfarin Select the most suitable anti-coagulant for the following. Mrs. Wong later changes to a drug that requires monitoring of clotting time, and is discharged from hospital with oral medication.

[Old PP] A. Acetylsalicylic acid / aspirin B. Antithrombin III C. Heparin D. Dabigatran E. Vitamin K F. Fibrinogen G. Tranexamic acid H. Thrombin I. Clopidogrel J. Warfarin Select the most suitable anti-coagulant for the following. Mrs Wong finds it troublesome to undertake clotting time monitoring and so doctor changes to a drug that does not require monitoring.

[Old PP] A. Acetylsalicylic acid / aspirin B. Antithrombin III C. Heparin D. Dabigatran E. Vitamin K F. Fibrinogen G. Tranexamic acid H. Thrombin I. Clopidogrel J. Warfarin Select the most suitable anti-coagulant for the following. Mr Chan suffered minor stroke, and is prescribed a drug to alleviate its recurrence. He finds out from Internet that the medication inhibits platelet and has a low cost.

[Old PP] A. Acetylsalicylic acid / aspirin B. Antithrombin III C. Heparin D. Dabigatran E. Vitamin K F. Fibrinogen G. Tranexamic acid H. Thrombin I. Clopidogrel J. Warfarin Select the most suitable anti-coagulant for the following. Mr Chan also finds out a more costly antiplatelet drug.

[Old PP] Warfarin is a commonly used anticoagulant drug for the prevention of thrombosis, and has a low therapeutic index. Warfarin exerts its effects by interfering with the vitamin K-mediated synthesis of clotting factors. Which of the following affects the dose requirement of this drug? A. Genetic alteration in CYP2C19 B. Genetic alteration in CYP2D6 C. Genetic alteration in VKORC1

[Old PP] Blood clotting is an important body regulatory process. Which enzyme activates plasminogen to plasmin? A. Adenylyl cyclase B. Cyclooxygenase C. Glucokinase D. Phospholipase E. Urokinase

E Thrombolytic / Fibrinolytic agents: - Alteplase - Streptokinase - Anistreplase - Urokinase

[Old PP] Mr. Li visits the doctor and was prescribed a drug to reduce the risk of stroke. Which of the following drugs is the most appropriate in reducing the risk of stroke? A. Acetylsalicylic acid (ASA) B. Clopidogrel C. Heparin D. Vitamin K E. Warfarin

A Low dose aspirin for primary prevention of MI and stroke

[Old PP] Which of the following is a potential cause for prolongation of thrombin time? A. F7 B. F13 C. Prothrombin deficiency D. Unfractionated heparin therapy E. Warfarin therapy

D By inhibition of thrombin TT: quantitative / qualitative abnormality of fibrinogen F13: crosslink fibrin(ogen)

[Old PP] Mrs. Cheung has atrial fibrillation. Which of the following can decrease her risk of having thromboembolism? A. Heparin B. Low molecular weight heparin C. Vitamin K D. Tranexamic acid E. Warfarin

E Warfarin: long-term Heparin: short-term / intermediate

[Old PP] Ultrasound indicated presence of deep vein thrombosis in a patient. What is the appropriate initial treatment for this condition? A. Aspirin B. Heparin C. Vitamin C D. Vitamin K E. Warfarin

[Old PP] Which properties, found in aspirin, are most useful for a patient who has suffered cerebrovascular disease? A. Anti-platelet B. Analgesic C. Anti-inflammatory D. Neuro-protective E. Thrombolytic

[PP] What is the MOST predominant class of naturally occurring antibodies against ABO antigens?

IgM

[PP] The discovery of ABO and Rh blood groups allows blood transfusion to occur safely. What blood group recipients can safely be transfused with any ABO and Rh blood types?

AB+ AB+: universal recipient O+: universal donor

[PP] Explain why B+ blood should not be transfused to an O+ patient. (3 marks)

- O+ patient contains anti-B antibodies in the serum - Anti-B antibodies will bind to B antigen on B+ blood of donor - leading to acute haemolytic transfusion reaction and intravascular haemolysis of the transfused blood

[PP] The ABO blood group of a person is inherited from his biological parents. What is/are the ABO genotype(s) of the offspring whose biological parents are of blood groups O and B? A. BB B. BB or OO C. BO D. BO or OO

[PP] ABO blood group of a person is genetically determined. What is/are the ABO genotype(s) of the offspring whose biological parents are of blood groups O and A? A. AO B. AA C. AO or OO D. AA or OO

[PP] The two major blood group systems that are important in blood typing before blood transfusion are the ABO and Rh blood groups. What is the chemical nature of those parts of ABO antigens that determine their abilities to induce specific antibodies? A. Carbohydrate B. Lipid C. Nucleic acid D. Protein

A Oligosaccharide on surface membrane glycoprotein of red cells

[PP] Fatal haemolytic transfusion reaction may occur after blood transfusion of mismatched blood groups. What blood group recipients can safely be transfused with group A blood? A. A or AB B. A or O C. B or AB D. B or O E. O or AB

[PP] Cecilia’s blood type is O+. During surgery, she was accidentally given wrong blood resulting in an ABO incompatibility and a haemolytic reaction within 24 hours. Which antibody subtype is mainly responsible for the haemolysis? A. Immunoglobulin A B. Immunoglobulin D C. Immunoglobulin E D. Immunoglobulin G E. Immunoglobulin M

[PP] Name one alternative to blood transfusion for managing an anaemic individual.

Iron replacement / Erythropoiesis-stimulating agents

[PP] Jane, a 35-year-old female, presented for an antenatal outpatient appointment. It was her first pregnancy and her blood sample was collected for blood grouping. It was found that Jane’s blood group is group B, RhD positive. Name two blood groups that Jane can receive in transfusion.

1. group O, RhD positive 2. group B, RhD positive

[PP] Briefly explain the principles of direct grouping and reverse grouping of blood.

1. Direct grouping - uses antisera to whole blood / RBCs - to determine presence of antigens, namely A / B / RhD 2. Reverse grouping - uses reagent red cells / red cells with known group - to test anti-A and anti-B antibodies in plasma / serum

[Old PP] Alpha-1,3-galactosyltransferase found in which types of blood cells? A. A and AB B. A and O C. B and AB D. B and O E. O and AB

C B allele encodes alpha-1,3-galactosyltransferase -> add galactose to H antigen -> B antigen A allele -> enzyme / glycosyltransferase -> add N-acetyl galactosamine to H antigen -> A antigen

[Old PP] Which of the following contributes to blood group of erythrocytes? A. Spectrin B. Actin C. Intracellular reticulin D. Haemoglobin E. Surface glycoproteins and glycolipids

[Old PP] Enzyme alpha N-acetyl galactosamine. Which blood group? A. A and AB B. A and O C. B and AB D. B and O E. O

[Old PP] Helen is Rh(D) negative and her husband is Rh(D) positive. In her third pregnancy, there is a high chance for her foetus to suffer from haemolytic disease of the newborn. Which of the following is the isotope of antibody against Rh(D)? A. IgG B. IgM C. IgA D. IgD E. IgE

A Warm-reacting IgG of mother crosses placenta -> attack RhD antigens on RBCs of foetus -> HDN

[Old PP] There are two methods used for blood banking, the needle-and-syringe and the closed system method. What is the single MOST important reason that the closed system method is preferred? A. Better practice of standard precaution B. Easier to have successful puncture C. Faster to finish blood taking D. Lower chance of cross contamination E. Lower cost

[Old PP] What is the BEST TIME to label a bottle for blood taking? A. At the nurse station where the patient’s file is available B. During blood taking C. Immediately after blood taking D. Immediately before blood taking E. In the clinical laboratory

[Old PP] Blood group test of a patient Patient’s red blood cell reacts with: Anti-A: 4+ Anti-B: 4+ Patient’s serum reacts with: A cells: negative B cells: negative A. A B. B C. AB D. O E. Non-A non-B

[Old PP] When you are taking multiple blood specimen for different laboratory tests, there are sets of orders to perform the tests, what is the rationale? A. Some tests are critically temperature-dependent B. Some tests are critically time-dependent C. Some tests are less tolerant to contamination D. Some tests are more important in management E. Some tests require fresher blood

[Old PP] Major adverse transfusion reactions may cause mortality. Which major adverse transfusion reaction is often a result of human error? A. ABO incompatible transfusion B. Anaphylaxis C. Transfusion-associated fluid overload D. Transfusion-associated graft-versus-host disease E. Transfusion-transmitted viral infection

[Old PP] Paroxysmal nocturnal haemoglobinuria (PNH) is characterised by the following except A. Intravascular haemolysis B. Extravascular haemolysis C. Dangerous thrombosis D. Acquired defects of red cell E. Negativity with DAT (direct antiglobulin test)

[Old PP] Use the fresh frozen plasma (FFP) is indicated in the following conditions EXCEPT A. Specific clotting factor deficiencies in which factor concentrate treatment is not available B. Bleeding in von Willebrand disease C. Supportive therapy in disseminated intravascular coagulation D. Thrombotic thrombocytopenic purpura E. Clinical coagulopathy in massive blood transfusion

[PP] Flow cytometry and fluorescence in-situ hybridisation (FISH) are two important investigational techniques in haematological malignancies. Regarding their test principles, give one similarity between these two techniques.

Both use fluorochrome-labelled material for investigation.

[PP] Describe the principle of FISH.

FISH uses single-stranded fluorescent/fluorophore-labelled genetic probes that hybridise to specific complementary genomic sequence(s) Subject to the design of probes, one can determine copy number variants, or determine the presence of genetic rearrangements e.g. fusion genes

[PP] For flow cytometry, provide one clinical scenario of haematological malignancies in which the technique is useful for diagnosis.

Identify lineage of abnormal cells in acute leukaemia or lymphoproliferative disease

[PP] For FISH, provide one clinical scenario of haematological malignancies in which the technique is useful for diagnosis.

Detect fusion genes in chronic myeloid leukaemia (BCR::ABL1) or acute promyelocytic leukaemia (PML::RARA); detect copy number variants in myelodysplastic neoplasm, e.g. -5/del(5q), -7/del(7q)

[PP] Which cells highly express HLA-DRB1 protein?

Antigen presenting cells (MHC class II) VS MHC class I: all nucleated cells

[PP] Describe the function of HLA-DRB1 protein.

Present antigen to CD4+ T cells -> induce T cell activation

[PP] Individuals with human leukocyte antigen (HLA)-DRB1*15 allele are more protected from HIV infection. Explain with three steps how HLA-DR polymorphism affects HIV control. (3 marks)

- Different alleles have different binding affinity towards peptide - which can affect the acidity of TCR recognition - leading to generation of HIV-specific CD4+ T cells with different strength

[PP] Nathan, a 30-year-old male, suffered from severe blood loss and required blood transfusion. His blood group is group A, RhD positive. Which of the following blood should he receive in transfusion? A. Group A, RhD negative B. Group AB, RhD positive C. Group B, RhD negative D. Group O, RhD positive

[PP] A routine blood typing was carried out for Nancy, a new-born infant. The results are shown below. Direct typing of red cells: Anti-A anti-serum: positive Anti-B anti-serum: negative Anti-D anti-serum: positive Reverse typing of serum: A reagent red cells: negative B reagent red cells: positive O reagent red cells: negative What is Nancy’s blood group? A. Group A, RhD negative B. Group A, RhD positive C. Group B, RhD negative D. Group B, RhD positive

[PP] Humoral immune responses A. Antigen presentation B. Bacterial peptides C. Bacterial polysaccharides D. Bacterial proteins E. Bone marrow F. Class switching G. Complement activation H. Germinal center I. Lymph nodes J. Somatic permutation B cells produce antibodies that protect us from infection. For each of the following questions, select the MOST RELEVANT option from the list above. Which antigens activate B cells?

[PP] Domains of healthcare quality A. Appropriate B. Cheap C. Disease-oriented D. Effective E. Efficient F. Equitable G. Patient-centred H. Safe I. Timely J. Useful For each of the following descriptions, select the corresponding domain of healthcare quality according to the Institute of Medicine (IOM) framework from the list of options above. Avoiding harm to patients from the care that is intended to help them

[PP] Domains of healthcare quality A. Appropriate B. Cheap C. Disease-oriented D. Effective E. Efficient F. Equitable G. Patient-centred H. Safe I. Timely J. Useful For each of the following descriptions, select the corresponding domain of healthcare quality according to the Institute of Medicine (IOM) framework from the list of options above. Providing services based on scientific knowledge to all who would benefit and refraining from providing services to those not likely to benefit.

D Appropriate, Cheap, Disease Oriented and Useful are not domains in IOM Efficient: avoiding waste (waste of equipment, supplies, ideas and energy) Equitable: providing care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographic location, and socioeconomic status Patient-centred: providing care that is respectful of and responsive to individual patient’s preferences, needs and values and ensuring that patient values guide all clinical decisions. Timely: reducing waits and sometimes delays for both those who receive and those who give care

[ALW] What is an “immunoconjugate” and what is the mechanism of action? Give an example of immunoconjugate.

Structure of antibody-drug conjugates (ADCs): - Link 1. mAb / antibody fragments - specific to a tumour cell-surface antigen + 2. cytotoxic agent / payload -> tumour-targeted killing MOA: 1. Binding of antibody to specific antigen 2. Internalisation of ADCs by target cell 3. Lysosomal degradation of antibody 4. Release of cytotoxic metabolite for tumour cell killing E.g. Brentuximab vedotin - For Hodgkin lymphoma - Against CD30 on lymphocytes - Cytotoxic agent = monomethyl auristatin E (MMAE): anti-microtubule agent (cleaved MMAE disrupts microtubule polymerisation)

[ALW] Based on the immune control of malignancies in healthy individuals, explain the mechanism of action of pembrolizumab.

Bind to PD-1 receptors on T cells => block the action of PD-L1 on tumour cells which inhibit T cell activation => induce T cell response PD-1: programmed cell death protein-1, negative costimulatory molecule with 2 ligands (PD-L1 / B7-H1, PD-L2, B7-DC) Also nivolumab

[ALW] Name the class of Adriamycin, Bleomycin, Vinblastine and Dacarbazine.

Anti-tumour antibiotics: Doxorubicin (=hydroxydaunorubicin, anthracycline), Bleomycin Mitotic inhibitor: Vinblastine (Vinca alkaloid) Dacarbazine: Alkylating agent For Hodgkin lymphoma

[ALW] State the mechanisms of action of Adriamycin and Bleomycin.

Adriamycin (doxorubicin): 1. Intercalate between base pairs of DNA / RNA 2. then, inhibit topoisomerase II -> prevent relaxation of supercoiled DNA -> DNA damage 3. then, interact with O2 to generate free radicals (oxidative) -> single-strand breaks, membrane lipid peroxidation, etc. Bleomycin: - copper-chelating - generate free radicals (oxidative) -> scission of DNA

[ALW] State the mechanisms of action of Vinblastine.

Mitotic inhibitor GTP-dependent tubulin binding -> prevent microtubule polymerisation -> dysfunctional spindles in metaphase -> prevent chromosomal segregation & cell proliferation

[ALW] State the mechanism of action of Dacarbazine.

Alkylating agent - Exert toxic effects by covalently binding to nucleophilic groups of various cell constituents - Alkylation of N7 of imidazole ring of guanine -> Base mispairing, DNA cross-linking & breakage (scission) -> inhibit DNA replication and cell proliferation

[ALW] ABVD is the most common drug combination for newly diagnosed Hodgkin lymphoma. At which HA Drug Formulary category should it be placed? Why?

General drugs (except liposomal doxorubicin: SFIs with safety net) 1. General drugs: well-established indications and cost-effectiveness, for general use for relevant clinical indications 2. Special drugs: under special clinical conditions under specialist authorisation 3. Self-financed items (SFIs) with safety net: expensive drugs with proven clinical benefits, safety net for patients in need to subsidise the expenses 4. Self-financed items (SFIs) without safety net: expensive drugs with preliminary evidence of clinical benefits or only marginal benefits

[ALW] Brentuximab vedotin and pembrolizumab are currently listed under SFI in both categories: with and without safety net. How do these two categories differ?

1. Difference in clinical indications / benefits - Proven significant clinical benefits VS preliminary evidence of clinical benefits / only marginal benefits over available alternatives 2. Difference in subsidy - SFIs with safety net: Samaritan Fund & Community Care (CCF) medical assistance programmes may subsidise the expenses of patients with financial difficulties if their medical conditions might be significantly improved - SFIs without safety net: no subsidy

[ALW] Under what circumstances may brentuximab vedotin and pembrolizumab be shifted from SFIs to Special drugs category? Suggest 2 leading principles.

1. Safety 2. Efficacy 3. Cost-effectiveness

[ALW] Clinical trials showed a satisfactory efficacy and safety of a new immunotherapy drug A and the drug was approved by the US Food and Drug Administration (FDA). However, the Hospital Authority Drug Advisory Committee (DAC) rejected the application to list the Drug under the General and Special categories. What three principles had a main impact on the DAC decision? Select one: A. Positive international recommendation, patients' experience and expert opinion. B. Cost-effectiveness, comparison with available alternatives, opportunity costs. C. Comparison with available alternatives, opportunity costs and disease state. D. Cost of illness, disease state and safety.

[ALW] A chief of a hematology laboratory at Hong Kong public hospital would like to purchase a new automatic blood analyser for the routine hematology testing. What three most important principles of Health Technology Assessment he needs to consider? Select one: A. Cost-utility, safety and quality. B. Cost-minimisation, practicality of implementation and ethics. C. Cost-effectiveness, safety and quality. D. Cost-benefits, safety and social impact.

[ALW] Which of the following helps to reduce the toxicity of doxorubicin? Select one: A. Flucytosine B. Carboplatin C. Amifostine D. Dexrazoxane

D Dexrazoxane - iron chelator - reduce metal ions complexed with anthracyclines -> less superoxide radicals -> less cardiotoxicity Liposomal-encapsulated doxorubicin is less cardiotoxic

[ALW] Which of the following is a long-acting glucocorticoid? Select one: A. Prednisolone B. Hydrocortisone C. Triamcinolone D. Dexamethasone

[PP] A 35-year-old man was presented with a 3 cm neck mass. Fine needle aspiration was performed which showed presence of tumour cells with nuclear inclusions and grooving, overlapping ground-glass nuclei and occasional multinucleated giant cells. What is the MOST LIKELY diagnosis? A. Anaplastic carcinoma B. Follicular carcinoma C. Medullary carcinoma D. Papillary carcinoma D Papillary carcinoma of thyroid - Nuclear grooves, Orphan Annie nuclei / pseudonuclear inclusions - overlapping ground-glass nuclei - multinucleated giant cells [PP] There are different types of thyroid malignancies. Which type of thyroid cancer has the HIGHEST risk of distant metastasis? A. Anaplastic thyroid cancer B. Follicular thyroid cancer C. Medullary thyroid cancer D. Papillary thyroid cancer A Anaplastic thyroid cancer (<5% of thyroid CA) - most aggressive: usually presents with locally advanced disease and distant metastasis (~15-50% of patients on presentation) - undifferentiated cells [PP] Surgically resected thyroid glands are always examined microscopically. Which of the following features, when found in combination, may confirm papillary carcinoma? A. Papillary structures associated with massive lymphoid cells infiltration B. Papillary structures associated with scalloped colloid in the same follicle C. Papillary structures covered by cells with hyperchromatic or enlarged nuclei D. Papillary structures covered by cells with Orphan Annie nuclei or nuclear grooves D [PP] Microscopic examination is essential for the diagnosis of papillary carcinoma of the thyroid. What is/are the key diagnostic feature(s)? A. Coexisting lymphocytic thyroiditis in the non-neoplastic gland B. Diffuse and severe nuclear atypia with irregular nuclear outline C. Nuclei with nuclear grooves and pseudonuclear inclusions D. Prominent papillary architecture with scalloping of colloid C

[PP] Some autoimmune markers are useful for disease monitoring. Which of the following antibody assays is commonly used for systemic lupus erythematosus monitoring? A. Anti-ds DNA antibodies B. Anti-extractable nuclear antigen antibodies C. Anti-neutrophil cytoplasmic antibodies D. Antinuclear antibodies

A SLE monitoring: anti-dsDNA, C3, C4

[PP] Some autoimmune markers are useful for disease monitoring. Which of the following tests is COMMONLY used as a diagnostic assay for connective tissue disease workup but NOT USEFUL for disease activity monitoring? A. Anti-ds DNA antibodies B. Anti-extractable nuclear antigen antibodies C. Anti-neutrophil cytoplasmic antibodies D. Complement measurement, i.e. C3, C4

B Anti-dsDNA, C3, C4: SLE monitoring Anti-dsDNA: SLE diagnosis Anti-extractable nuclear antigen (Anti-ENA): diagnosis

[PP] Regulatory T cells are important in self tolerance. Which of the following BEST describes regulatory T cells? A. Regulatory T cells are developed in the bone marrow B. Regulatory T cells are important components in central tolerance C. Regulatory T cells belong to the subset of cytotoxic T cells D. Regulatory T cells delete autoreactive cells in the thymus E. Regulatory T cells mediate immunosuppressive effect

E Tregs A: thymus B: peripheral tolerance C: CD4+ CD25+ helper T cells D. Deletion of autoreactive cells = central tolerance Tregs suppress autoreactive T cells by producing cytokines (TGF-beta, IL-10)

[Self-assessment] Which of the following test is most commonly arranged as initial workup for connective tissue disease conditions (e.g. systemic lupus erythematosus) : a. anti-nRNP antibody b. anti-Ro antibody c. anti-nuclear antibody d. anti-dsDNA antibody e. anti-cardiolipin antibody

c ANA: sensitive -> screening Others: specific -> further investigations if suspicion (diagnosis, monitoring)

[PP] Membrane phospholipids of platelets are actively involved in the formation of coagulation complexes. Which of the following phospholipids will be exposed to the outer surface of activated platelets? A. Phosphatidic acid B. Phosphatidylcholine C. Phosphatidylethanolamine D. Phosphatidylserine

[PP] PATHOPHYSIOLOGY OF DISEASES A. Carnitine uptake deficiency B. Clotting factor deficiency C. Glucose-6-phosphatase deficiency D. Glucose-6-phosphate dehydrogenase deficiency E. Hepcidin deficiency F. Hepcidin in excess G. Inhibition of angiotensin converting enzyme H. Inhibition of cyclo-oxygenase-2 I. Non-specific inhibition of cyclo-oxygenases J. Venous thromboembolism For each of the following patients, select the MOST PROBABLE pathological cause of the clinical outcomes from the list of options above. Each option may be used once, more than once, or not at all. Question 20 A 65-year-old woman had been taking an anti-inflammatory drug for treating arthritis. Today she is admitted following an ischaemic stroke.

[PP] In erythrocytes, the Fe(II) state of haemoglobin is maintained by NADPH. NADPH is regenerated from NADP as shown. Which metabolite supplies the electrons for the recycling of NADP to NADPH? A. Fructose 6-phosphate B. Glucose 6-phosphate C. Glyceraldehyde 3-phosphate D. Glycerol 3-phosphate

[PP] Name one form of anaemia that can result from oxidative damage of erythrocytes. (1 mark)

Haemolytic anaemia due to G6PD deficiency

[PP] Apart from supplying energy to support erythrocyte function, glucose also serves to mitigate oxidative stress in these cells. Briefly explain how. (2 marks)

1. Pentose phosphate pathway: G6PD uses G6P from glucose to reduce NADP to NADPH 2. Glutathione reductase uses NAPHD to reduce GS-SG (oxidised glutathione) to GSH (reduced glutathione) 3. Glutathione peroxidase uses GSH to reduce H2O2 to harmless H2O -> prevent oxidation of Hb

[PP] Red cell metabolism serves to protect these cells from intracellular oxidation. Name two sources of hydrogen peroxide that contribute to oxidative stress in erythrocytes. (2 marks)

1. ROS including superoxide anion radical (produced by other tissue cells by mitochondrial ETC / by activated neutrophils and macrophages) -> reduced by superoxide dismutase to H2O2 (non-radical ROS) 2. Oxidant stress (fava beans, infections, certain drugs)

[ALW] What are the important questions you will ask a patient presenting with bleeding symptoms?

Family history (congenital bleeding disorders) Medical history (past surgery e.g. tooth extraction -> any excessive bleeding, trauma) Menstrual history in women Symptoms of cytopenia (anaemia, fever) Personal history (age of onset, severity, progression)

[ALW] Mr. Seto, 81-years old, was edmitted to the general medical ward for a 1 week history of haematuria, He was a non-smoker with pest history of hypertension that was wellcontrolled with one antihypertensive agent. He had no previous history of haematuria.On physical examination, large bruises were observed over the lower back.Preliminary investigations were performed. Complete blood count: White blood cell count 6,41 x 10°/L (Normal: 3.89-9,93 x 10°/L) Haemoglobin 10.5 g/dl (Normal: 11.5-14.8 g/dL) Mean corpuscular volurne 80 fL (Normal: 82,0-95.5 fL) Platelet count 455 x 10^9/L (Normal: 167-396 x10^9/L) Blood film review showed no abnormal cells. Polychromasia was absent. Occasional hypochromic and microcytic cells were observed Clotting profile showed: PT 12 seconds (Normal: 10,9-13.6 seconds) APTT 90.2 seconds (Normal: 25.1-33.9 seconds) Iron profile confirmed iron deficiency. The renal and liver function tests were normal. What is the most likely cause of anaemia and thrombocytosis in this patient?

Iron deficiency anaemia with reactive thrombocytosis

[ALW] Mr. Seto, 81-years old, was edmitted to the general medical ward for a 1 week history of haematuria, He was a non-smoker with pest history of hypertension that was wellcontrolled with one antihypertensive agent. He had no previous history of haematuria.On physical examination, large bruises were observed over the lower back.Preliminary investigations were performed. Complete blood count: White blood cell count 6,41 x 10°/L (Normal: 3.89-9,93 x 10°/L) Haemoglobin 10.5 g/dl (Normal: 11.5-14.8 g/dL) Mean corpuscular volurne 80 fL (Normal: 82,0-95.5 fL) Platelet count 455 x 10^9/L (Normal: 167-396 x10^9/L) Blood film review showed no abnormal cells. Polychromasia was absent. Occasional hypochromic and microcytic cells were observed Clotting profile showed: PT 12 seconds (Normal: 10,9-13.6 seconds) APTT 90.2 seconds (Normal: 25.1-33.9 seconds) Iron profile confirmed iron deficiency. The renal and liver function tests were normal. 1:1 mixing study is performed, APTT is not corrected after incubation with normal plasma. Factor VIII level is below normal. What is the most likely diagnosis? What is the first-line treatment?

Acquired haemophilia A (autoantibodies against factor VIII) Tx: immunosuppressants to eradicate inhibitor (e.g. prednisolone), treat acute bleeding

[ALW] What are the differences between the in vitro and in vivo coagulation cascades?

1. Intrinsic & extrinsic pathways: in vitro but not in vivo 2. Factor XII: important in vitro but not in vivo (deficiency causes no bleeding disorder at all) 3. Amplification / Positive feedback in vivo: - thrombin can activate factor XI -> further activate factor IX (=> factor XI deficiency causes only a mild bleeding disorder) - factor Xa (+) factor VIII & factor V Similarities: Both activate prothrombin to thrombin -> form fibrin clot Both require calcium

[Self-assessment] For in vivo condition, which clotting factor is dispensable for normal coagulation function? a. Factor V b. Factor XII c. Factor VII d. Factor X

b Factor V & X: activate prothrombin in vivo Factor VII: activate factor IX in vivo

[Self-assessment] Which clotting factor is vitamin K-dependent? a. Factor XI b. Factor VIII c. Factor VII d. Factor V

C Factor II, VII, IX, X

[Self-assessment] For in vitro condition, which clotting factor is directly activated by negatively charged glass beads? a. Factor VII b. Factor XII c. Factor V d. Factor XI

B Factor VII: activated by tissue factor Factor V: activated by factor Xa Factor XI: activated by factor XIIa

[ALW] What are the causes of isolated prolonged APTT in general?

Deficiency or inhibitor of factor VIII, IX, XI, XII, contact factor Lupus anticoagulant

[PP] a-thalassaemia is most attributed to deletion of a-globin genes. Which method is BEST used for detection of unknown large deletions? A. Allelic specific PCR B. Amplification-Refractory Mutation System C. Gap-PCR D. Multiplex Ligation-Dependent Probe Amplification

D Allelic specific PCR: known SNPs ARMS: multiple known point mutations RFLP: one known point mutation Gap PCR: large known deletions MLPA: unknown deletions

[PP] Health care organisations globally and regionally aim to provide high quality services. What organisation does provide mainly international recommendations for health care quality improvement? A. Department of Health of Hong Kong B. Health Technology Assessment Centre in Australia C. Hospital Authority in Hong Kong D. National Institute for Health and Care Excellence in UK

[PP] Economic evaluation is needed to make informed decision in health care. Which economic evaluation does measure outcomes and benefits in monetary values? A. Cost-benefit B. Cost-effectiveness C. Cost-minimisation D. Cost-utility

[PP] A doctor prescribed a newly approved drug which had entered the market after completion of the clinical trial. After two days, the patient presented to the emergency room with syncope, the ECG showed features of Torsades de Pointes. A doctor considered that a syncope might be due to an adverse reaction of a new drug, but could not find any information about Torsades de Pointes in the information leaflet. What would be a good source of information for medication safety surveillance at this stage? A. Adverse event reporting systems B. NICE systematic review C. Phase II trial results D. Phase III trial results

[PP] A 38-year-old man presented with dyspnoea. Chest X-ray showed a large mediastinal mass with tracheal deviation. CT-guided biopsy of the mediastinal mass revealed an infiltration by sheets of medium-sized lymphoid cells with high nuclear-to-cytoplasmic ratio, slightly condensed chromatin and irregular nuclear contour. Immunohistochemical staining highlighted the medium-sized lymphoid cells are T cells (CD3-positive) with immature phenotype (CD34-positive, Tdt-positive). The abnormal cells were negative for myeloid markers and B-cell markers. Complete blood count was normal. Peripheral blood smear and bone marrow examination were normal, with no evidence of abnormal T cell population. What is the MOST LIKELY diagnosis? A. Primary mediastinal large B-cell lymphoma B. Reactive proliferation of T cells C. T-lymphoblastic leukaemia D. T-lymphoblastic lymphoma

[PP] A 60-year-old man was diagnosed to have plasma cell myeloma and now he is planned to have autologous haemopoietic stem cell transplant. Which of the followings is one of the important properties of haemopoietic stem cell? A. Continuous cell cycle progression B. Continuous proliferation C. Dormancy D. Resistance to apoptosis

[PP] Matching of which of the following is considered important for allogeneic haematopoietic stem cell transplant? A. ABO blood group B. Age C. Gender D. Human Leucocyte Antigen (HLA)

[PP] A 45-year-old man developed unilateral right calf swelling two days after right hip replacement. Which of the following investigation should be ordered immediately? A. Antithrombin, protein C and protein S level B. D-dimer level C. Ultrasound doppler of right lower limb venous system D. X-ray of right lower limb

[PP] John felt very tired and his skin turned yellow after exposure to menthol. He was later found with anemia and jaundice. Which of the following deficiencies causes his conditions? A. Clotting factor XI B. Glucose-6-phosphatase C. Glucose-6-phosphate dehydrogenase D. Hepcidin

[PP] T lymphocytes can recognise and eliminate virus-infected cells. Which structure is responsible for presenting viral antigens to T cells? A. B cell receptor B. Beta-2 microglobulin C. HLA-DM D. T cell receptor

B MHC Class I: alpha chains (polymorphic), beta-2 microglobulin (non-polymorphic) MHC Class II: alpha, beta chains (polymorphic) HLA-DM: for intracellular peptide loading onto MHC class II molecules

[PP] Beti-cel is the first potentially curative gene therapy for transfusion-dependent beta thalassemia. The FDA approval for the use of beti-cel was given in August 2022. What is the genetic modification in this gene therapy? A. Addition of an alpha-globin gene B. Addition of a beta-globin gene C. Disruption of an alpha-globin gene D. Disruption of a beta-globin gene

[PP] CD8+ T cells recognise peptide antigens presented by MHC molecules. From which subcellular compartment are CD8 immunogenic peptides mainly derived? A. Endocytic vesicle B. Endoplasmic reticulum C. Golgi body D. Nucleus

[PP] A patient with lung cancer underwent surgery to remove a lobe of the left lung. Following the surgery, a sample of his pleural fluid appeared white. Which structure was MOST LIKELY damaged during the surgery? A. Azygos vein B. Cisterna chyli C. Oesophagus D. Thoracic duct

D In mediastinum VS cisterna chyli in abdomen

[PP] Which type of cell immediately surrounds central artery in spleen? A. Endothelial cell B. Erythrocyte C. Reticular cell D. T lymphocyte

D Periarterial lymphatic sheath (PALS)

[Self-assessment] A patient was mistakenly administered vincristine instead of cytarabine intrathecally. What is the likely outcome of this drug error? Select one: Rash Death Neuropathy Renal failure Hearing loss

Death

[Self-assessment] A patient is about to undergo three cycles of chemotherapy prior to surgery for bladder cancer. Which best describes chemotherapy in this setting? Select one: Maintenance Palliative Adjuvant Induction Neoadjuvant

Neoadjuvant - before surgery to shrink the cancer Adjuvant: after surgery to attack micrometastases Maintenance: low doses to prolong remission

[Self-assessment] A 45-year-old man is being treated with ABVD chemotherapy for Hodgkin lymphoma. He presents a new- onset cough for a week and has a little trouble catching his breath. Which drug in the ABVD regimen is the most likely cause of his pulmonary toxicity? Select one: Vincristine Dacarbazine Doxorubicin (Adriamycin) Vinblastine Bleomycin

Bleomycin Pulmonary fibrosis caused by Bleomycin = Bleomycin lung Milder: rales, coughs

[PP] A patient is about to begin therapy with doxorubicin and cyclophosphamide. Which test should be ordered for baseline assessment before treatment? Select one: Baseline pulmonary function tests Baseline echocardiogram Baseline liver function tests Baseline renal function tests Baseline stress tests

Baseline echocardiogram

[Self-assessment] Which chemotherapy drug can cause nephrotoxicity, neurotoxicity, ototoxicity, electrolyte abnormalities, and severe nausea and vomiting? Select one: Cisplatin Etoposide Paclitaxel Methotrexate Cyclophosphamide

Cisplatin

[Self-assessment] Which of the following should be ordered for a patient to be treated with cyclophosphamide? Select one: IV hydration, mesna and frequent urinalyses Allopurinol and frequent urinalyses IV hydration, prophylactic antibiotics and frequent urinalyses Leucovorin and frequent urinalyses Dexamethasone, diphenhydramine and frequent urinalyses

IV hydration, mesna and frequent urinalyses

[Self-assessment] Which of the following is inhibited by myeloma cells and, thereby myeloma patients are predisposed to bone complications? a. Chondrocytes b. Osteoblast c. Osteoclast

B ALP is usually normal unless bone fractures

HIS Important Questions Flashcards

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