Short Answer Qs Flashcards
(155 cards)
1
Q
What is the primary source of Vitamin B12?
A
Found in animal products (meat, dairy)
Vitamin B12 is crucial for various bodily functions.
2
Q
What binds to Vitamin B12 during the gastric phase of absorption?
A
R-binder (haptocorrin) secreted by salivary glands
This initial binding is essential for the protection of B12 in the stomach.
3
Q
In which part of the digestive system does Vitamin B12 bind to Intrinsic Factor (IF)?
A
In the duodenum
Intrinsic Factor is secreted by parietal cells and is crucial for B12 absorption.
4
Q
What receptors does the B12-IF complex bind to for absorption?
A
Specific receptors (cubilin)
This binding occurs in the terminal ileum.
5
Q
What transport protein carries Vitamin B12 to tissues?
A
Transcobalamin II
This protein is responsible for the delivery of B12 throughout the body.
6
Q
What are the clinical consequences of Vitamin B12 deficiency?
A
Megaloblastic anemia, neurological symptoms (subacute combined degeneration)
These symptoms highlight the importance of B12 in red blood cell formation and nerve function.
7
Q
What gene is mutated in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A
PIGA gene
This mutation leads to a deficiency of GPI-anchored proteins.
8
Q
What is the pathophysiological consequence of the lack of CD55/CD59 in PNH?
A
Complement-mediated intravascular hemolysis
This results in the destruction of red blood cells.
9
Q
What are the clinical features of Paroxysmal Nocturnal Hemoglobinuria?
A
Hemoglobinuria (especially in the morning), pancytopenia, thrombosis
These symptoms are critical for diagnosis and management.
10
Q
How is Paroxysmal Nocturnal Hemoglobinuria diagnosed?
A
Flow cytometry for CD55/CD59 deficiency on RBCs and granulocytes
This diagnostic method is essential for confirming PNH.
11
Q
What is the composition of Hemoglobin H?
A
Composed of β4 tetramers
This structure is indicative of a specific type of thalassemia.
12
Q
What condition is Hemoglobin H associated with?
A
Alpha-thalassemia (HbH disease) with 3 gene deletions
This genetic aspect is crucial for understanding the disease’s etiology.
13
Q
What is the pathophysiological consequence of excess β-chains in Hemoglobin H?
A
Unstable HbH → ineffective erythropoiesis & hemolysis
This leads to various clinical symptoms.
14
Q
What are the clinical manifestations of Hemoglobin H disease?
A
Moderate anemia, splenomegaly, Heinz bodies
These features are important for clinical recognition.
15
Q
What is the role of Pyruvate Kinase in red blood cell metabolism?
A
Converts phosphoenolpyruvate (PEP) to pyruvate, generating ATP
This is the final step in glycolysis, vital for RBC energy.
16
Q
Why is Pyruvate Kinase important for red blood cells?
A
RBCs rely on glycolysis for energy (lack mitochondria)
This metabolic pathway is their primary source of ATP.
17
Q
What is the consequence of Pyruvate Kinase deficiency?
A
Chronic hemolytic anemia due to energy depletion
This leads to cell rigidity and destruction.
18
Q
What causes Hemophilia A?
A
Factor VIII deficiency, X-linked recessive
This genetic disorder primarily affects males.
19
Q
What causes Hemophilia B?
A
Factor IX deficiency, X-linked recessive
Similar to Hemophilia A, this condition also predominantly affects males.
20
Q
How does the severity of Hemophilia correlate with factor levels?
A
Severe: <1%, Moderate: 1-5%, Mild: 5-40%
Understanding these levels is crucial for treatment planning.
21
Q
What do one-stage clotting assays measure?
A
Activity of specific coagulation factors (VIII, IX, XI)
These assays are primarily used for diagnosing bleeding disorders.
22
Q
Which conditions are diagnosed using one-stage clotting assays?
A
Hemophilia A (↓FVIII), Hemophilia B (↓FIX)
Hemophilia A is characterized by a deficiency of factor VIII, while Hemophilia B involves a deficiency of factor IX.
23
Q
What is the purpose of mixing studies in coagulation testing?
A
Differentiate between factor deficiency and inhibitor presence
This is crucial for accurate diagnosis and treatment planning in bleeding disorders.
24
Q
How can factor deficiency be confirmed?
A
Chromogenic assays and genetic testing if needed
These methods provide additional confirmation beyond initial screening tests.
25
What matrix proteins are exposed after vascular injury?
Collagen, von Willebrand Factor (vWF)
## Footnote
The exposure of these proteins is critical in initiating the coagulation process.
26
What initiates platelet adhesion after vascular injury?
GPIb-vWF interaction
## Footnote
This interaction is essential for platelet adhesion to the subendothelial matrix.
27
What triggers the coagulation cascade after vascular injury?
Release of tissue factor (TF)
## Footnote
This release leads to thrombin generation and subsequent fibrin clot formation.
28
What is the function of GPIb-IX-V?
Platelet adhesion to subendothelial vWF
## Footnote
This receptor plays a key role in the initial stages of hemostasis.
29
What ligands activate GPVI & Integrin α2β1?
Collagen
## Footnote
Activation of these receptors is crucial for platelet activation during hemostasis.
30
What is the function of GPIIb/IIIa (αIIbβ3)?
Platelet aggregation
## Footnote
This receptor binds fibrinogen and vWF to facilitate platelet clumping.
31
What amplifies platelet activation via P2Y12 receptor?
ADP
## Footnote
ADP is a key signaling molecule that enhances platelet activation.
32
What is the role of PAR-1/PAR-4 in platelet function?
Potent platelet activation
## Footnote
These receptors respond to thrombin, a key enzyme in the coagulation cascade.
33
What does EQA stand for in the context of hematology?
External Quality Assessment
## Footnote
EQA programs are essential for maintaining laboratory standards and accuracy.
34
What does regular participation in EQA help to detect?
Analytical errors
## Footnote
Participation ensures laboratories comply with testing standards and improves performance.
35
What are some advantages of Point-of-Care Testing (POCT) in coagulation?
* Rapid results (e.g., INR, D-dimer)
* Bedside testing in critical care
* Useful in emergency situations
* Enhances clinical decision-making
## Footnote
POCT provides immediate information that can be crucial in urgent care scenarios.
36
What are some disadvantages of POCT/NPT in coagulation?
* Potentially lower accuracy
* Requires strict quality control
* Higher cost per test
* May lack full analyte range
## Footnote
These factors must be considered when implementing POCT in clinical settings.
37
What is Nested PCR?
Two-step PCR amplification to increase specificity and sensitivity
## Footnote
This technique is particularly useful for detecting low-copy DNA.
38
What is the first step in Nested PCR?
First PCR amplifies a broad target region
## Footnote
This step lays the foundation for the more specific second PCR amplification.
39
What is the temperature range for LAMP (Loop-Mediated Isothermal Amplification)?
~60-65°C
## Footnote
LAMP is advantageous because it does not require thermal cycling.
40
What is one application of LAMP?
Point-of-care malaria diagnosis
## Footnote
LAMP is particularly beneficial in low-resource settings due to its rapid and sensitive nature.
41
What type of inheritance pattern does Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency follow?
X-linked recessive
42
What is the consequence of decreased NADPH in G6PD Deficiency?
Decreased reduced glutathione, making RBCs susceptible to oxidative damage
43
What can trigger a hemolytic crisis in G6PD Deficiency?
Infections, fava beans, drugs (e.g., primaquine, sulfa drugs)
44
What abnormal findings are seen on a blood film in G6PD Deficiency?
Heinz bodies and bite cells
45
How is G6PD Deficiency diagnosed?
G6PD enzyme assay
46
What is the role of von Willebrand Factor (vWF) in haemostasis?
Mediates platelet adhesion to subendothelium via GPIb receptor
47
What additional function does von Willebrand Factor serve?
Acts as a carrier for Factor VIII, protecting it from degradation
48
What condition results from vWF deficiency?
Von Willebrand disease
49
What are the clinical manifestations of von Willebrand disease?
Mucocutaneous bleeding
50
What type of disorder is Chronic Myeloid Leukaemia (CML)?
Clonal myeloproliferative disorder
51
What is the characteristic genetic alteration in CML?
Philadelphia chromosome: t(9;22) → BCR-ABL fusion gene
52
What is the result of the BCR-ABL fusion gene in CML?
Constitutive tyrosine kinase activity
53
What are common clinical presentations of CML?
Splenomegaly, leukocytosis
54
What is the standard treatment for CML?
Tyrosine kinase inhibitors (e.g., imatinib)
55
What causes Hereditary Spherocytosis (HS)?
Autosomal dominant defects in RBC membrane proteins (ankyrin, spectrin)
56
What is the consequence of membrane loss in HS?
Formation of spherocytes and splenic destruction leading to hemolytic anemia
57
How is Hereditary Spherocytosis diagnosed?
Osmotic fragility test, EMA binding assay
58
What are the treatments for Hereditary Spherocytosis?
Folic acid, splenectomy
59
What is the purpose of External Quality Assessment (EQA) in Haematology?
Ensures accuracy and reliability of lab results via inter-laboratory comparisons
60
What issues does EQA help identify?
Analytical errors, instrument calibration issues
61
Is EQA mandatory for laboratory accreditation?
Yes, it is mandatory (ISO 15189)
62
What is a key benefit of EQA in laboratories?
Continuous quality improvement tool
63
What binds to Intrinsic Factor in the absorption of Vitamin B12?
Vitamin B12
## Footnote
Intrinsic Factor is produced by gastric parietal cells.
64
Where is Vitamin B12 absorbed?
Terminal ileum
## Footnote
Absorption occurs via receptor-mediated endocytosis.
65
What conditions are required for Vitamin B12 absorption?
Acidic pH, pancreatic enzymes, intact ileum
## Footnote
These factors are essential for proper absorption.
66
In which conditions is there malabsorption of Vitamin B12?
Pernicious anaemia, terminal ileum diseases
## Footnote
These conditions affect the absorption process.
67
What are CAR T Cells?
Chimeric Antigen Receptor T-cells
## Footnote
They are genetically engineered to target tumour antigens.
68
In which type of malignancies is CAR T Cell Therapy used?
Refractory B-cell malignancies
## Footnote
This therapy is designed for cancers that do not respond to standard treatments.
69
What are potential side effects of CAR T Cell Therapy?
Cytokine Release Syndrome (CRS), neurotoxicity
## Footnote
These are serious complications that can arise from the therapy.
70
What is an example of adoptive immunotherapy?
CAR T Cell Therapy
## Footnote
This therapy utilizes the patient's own immune cells to fight cancer.
71
What genetic alteration is associated with Chronic Myeloid Leukemia (CML)?
t(9;22) → BCR-ABL fusion gene
## Footnote
This translocation results in the formation of an oncogene.
72
What does the BCR-ABL fusion gene encode?
A constitutively active tyrosine kinase
## Footnote
This enzyme promotes cell proliferation and inhibits apoptosis.
73
What do targeted therapies for CML, such as imatinib and dasatinib, inhibit?
BCR-ABL tyrosine kinase
## Footnote
These drugs are designed to block the activity of the fusion protein.
74
What mutation is associated with Factor V Leiden?
Point mutation (Arg506Gln) in Factor V gene
## Footnote
This mutation leads to resistance to activated Protein C.
75
What is the consequence of persistent Factor V activity?
Increased thrombin generation, thrombosis
## Footnote
This results in a higher risk of blood clots.
76
What is the most common inherited thrombophilia?
Factor V Leiden Mutation
## Footnote
This condition increases the risk of venous thrombosis.
77
How is Factor V Leiden diagnosed?
APC resistance assay, genetic testing
## Footnote
These tests confirm the presence of the mutation.
78
What pre-analytical variable can affect coagulation testing results?
Incorrect citrate ratio
## Footnote
Underfilling a sample can lead to inaccurate results.
79
What can delayed sample processing lead to in coagulation testing?
Factor degradation
## Footnote
Timely processing is crucial for accurate results.
80
What factors can cause artefacts in coagulation testing?
Hemolysis, lipemia, improper storage
## Footnote
These conditions can alter test outcomes.
81
What practices are essential for proper coagulation testing?
Proper phlebotomy, prompt transport, centrifugation
## Footnote
These steps ensure sample integrity and accuracy of results.
82
What is the function of Antithrombin (AT)?
Inhibits thrombin & Factor Xa
## Footnote
Antithrombin is a natural anticoagulant that plays a crucial role in regulating blood coagulation.
83
What does Protein C do when activated?
Degrades Factors Va & VIIIa
## Footnote
Protein C is an important regulatory protein in the coagulation cascade.
84
What is the role of Protein S?
Cofactor for Protein C
## Footnote
Protein S assists Protein C in its anticoagulant function.
85
What is the consequence of Protein C or S deficiency?
Leads to hypercoagulability
## Footnote
Deficiencies in these proteins can increase the risk of thrombosis.
86
What changes occur in the subendothelium after vascular injury?
Exposure of collagen, vWF, tissue factor
## Footnote
These changes are critical for initiating the coagulation process.
87
What initiates platelet adhesion and activation?
vWF & GPIb
## Footnote
von Willebrand factor (vWF) plays a key role in platelet function.
88
What pathway is initiated during the coagulation cascade after vascular injury?
Extrinsic pathway
## Footnote
The extrinsic pathway is triggered by tissue factor exposure.
89
What is formed as a result of the coagulation cascade?
Haemostatic plug
## Footnote
The haemostatic plug is essential for stopping bleeding.
90
What is the shape of the oxygen dissociation curve?
Sigmoidal shape
## Footnote
This shape reflects the cooperative binding of oxygen to hemoglobin.
91
What causes a right shift in the oxygen dissociation curve?
↑ CO2, ↑ temperature, ↑ 2,3-BPG, ↓ pH
## Footnote
A right shift indicates decreased affinity of hemoglobin for oxygen.
92
What conditions lead to a left shift in the oxygen dissociation curve?
Opposite conditions of right shift
## Footnote
A left shift indicates increased affinity for oxygen.
93
Why is the oxygen dissociation curve important?
Important in oxygen delivery to tissues
## Footnote
The curve helps understand how hemoglobin releases oxygen under different physiological conditions.
94
What is the purpose of High-Performance Liquid Chromatography (HPLC) in hemoglobinopathies?
Separates haemoglobin variants
## Footnote
HPLC is a key diagnostic tool for various blood disorders.
95
What does HPLC quantify in hemoglobin analysis?
HbA, HbA2, HbF, abnormal Hbs (e.g., HbS, HbC)
## Footnote
This quantification is critical for diagnosing conditions like sickle cell disease and thalassemia.
96
What is the structure of Adult Hemoglobin (HbA)?
Tetramer: 2 alpha and 2 beta chains
## Footnote
This structure allows hemoglobin to effectively transport oxygen.
97
How many oxygen molecules can each hemoglobin molecule bind?
4 oxygen molecules per Hb
## Footnote
Each of the four heme groups in hemoglobin binds one oxygen molecule.
98
What is the principle of cooperative binding in hemoglobin?
Efficient O2 transport
## Footnote
Cooperative binding enhances the ability of hemoglobin to pick up and release oxygen.
99
What is the action of Warfarin?
Inhibits Vitamin K epoxide reductase
## Footnote
This action decreases the activation of several clotting factors.
100
What clotting factors are affected by Warfarin?
Factors II, VII, IX, X
## Footnote
Warfarin's effect on these factors is crucial for its anticoagulant properties.
101
How is Warfarin monitored?
Using Prothrombin Time (PT) / INR
## Footnote
Monitoring is essential due to Warfarin's narrow therapeutic index.
102
What is a key characteristic of Warfarin therapy?
Narrow therapeutic index
## Footnote
This characteristic necessitates careful dose adjustments to avoid complications.
103
What are the stages of granulopoiesis?
Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band cell → Mature granulocyte
104
What biochemical changes occur during the promyelocyte stage of granulopoiesis?
Synthesis of primary (azurophilic) granules
105
What biochemical changes occur during the myelocyte stage of granulopoiesis?
Synthesis of secondary granules, chemotactic receptors, cytoplasmic enzymes
106
Describe the morphological changes in granulopoiesis.
Gradual nuclear condensation, lobulation, cytoplasm changes from basophilic to eosinophilic
107
What is the laboratory investigation for G6PD deficiency?
Enzyme assay after haemolytic episode, fluorescence spot test
108
What is the laboratory investigation for Pyruvate Kinase deficiency?
PK enzyme assay, increased 2,3-BPG levels
109
How is Pyruvate Kinase deficiency confirmed in familial cases?
Genetic testing
110
List risk factors for haematological malignancies.
* Genetic predisposition (e.g., Down syndrome, Fanconi anaemia)
* Radiation exposure
* Chemicals (benzene)
* Viral infections (EBV, HTLV-1)
* Immunosuppression
* Aging
* Smoking
111
What laboratory roles are involved in leukaemia diagnosis?
* FBC & blood film (blasts, anaemia, thrombocytopenia)
* Bone marrow biopsy
* Immunophenotyping by flow cytometry
* Cytogenetics (Philadelphia chromosome)
* Molecular testing (PCR, FISH)
112
What are rapid bedside tests in Point of Care Testing (POCT) in haematology?
INR, D-dimer, Hb levels
113
What are the advantages of Point of Care Testing (POCT)?
Fast results, critical care use
114
What are the disadvantages of Point of Care Testing (POCT)?
Less sensitive, quality control challenges
115
Where is iron absorbed in the body?
Duodenum via DMT1 transporter
116
How is iron exported from cells?
By ferroportin, aided by hephaestin
117
What regulates iron absorption?
Hepcidin (inhibits ferroportin)
118
What enhances iron absorption?
Vitamin C
119
What substances reduce iron absorption?
Phytates, calcium
120
What mutation causes Sickle Cell Anaemia?
Mutation in beta-globin gene (Glu6Val)
## Footnote
This mutation leads to the formation of HbS.
121
What occurs when deoxygenated HbS polymerizes?
RBC sickling
## Footnote
This sickling can lead to vaso-occlusive crises and haemolysis.
122
How is Sickle Cell Anaemia diagnosed?
Hb electrophoresis/HPLC
## Footnote
These methods are used to identify the presence of HbS.
123
What is erythropoiesis?
Production of RBCs from HSCs in bone marrow
## Footnote
HSCs refer to hematopoietic stem cells.
124
What stimulates erythropoiesis?
Erythropoietin (EPO) from kidneys
## Footnote
EPO is a hormone that regulates RBC production.
125
List the stages of erythropoiesis.
* Pronormoblast
* Basophilic
* Polychromatic
* Orthochromatic
* Reticulocyte
* Mature RBC
## Footnote
These stages represent the maturation process of red blood cells.
126
What is the first test for diagnosing Antiphospholipid Syndrome (APS)?
Lupus anticoagulant (LA) detection: dRVVT, aPTT assays
## Footnote
These assays help identify the presence of lupus anticoagulant.
127
What antibodies are tested for in APS?
* Anticardiolipin antibodies (IgG, IgM)
* Anti-β2 glycoprotein I antibodies
## Footnote
These antibodies are associated with increased risk of thrombosis in APS.
128
When should tests for APS be confirmed?
At 12 weeks
## Footnote
Confirmation is necessary to establish a diagnosis.
129
What do Howell-Jolly bodies indicate?
Splenic dysfunction
## Footnote
Howell-Jolly bodies are remnants of DNA in RBCs, typically removed by a healthy spleen.
130
What condition is associated with Heinz bodies?
G6PD deficiency
## Footnote
Heinz bodies are formed due to oxidative damage in RBCs.
131
What does basophilic stippling indicate?
Lead poisoning
## Footnote
Basophilic stippling is characterized by the presence of small blue granules in RBCs.
132
What are Pappenheimer bodies associated with?
Sideroblastic anaemia
## Footnote
These bodies represent iron deposits in RBCs.
133
What is extravascular haemolysis?
RBCs destroyed in spleen/liver by macrophages
## Footnote
It is a process often seen in certain hemolytic anemias.
134
What conditions are associated with extravascular haemolysis?
* Hereditary spherocytosis
* Autoimmune haemolytic anaemia
## Footnote
These conditions lead to increased destruction of RBCs.
135
What are the signs of extravascular haemolysis?
* Splenomegaly
* Unconjugated hyperbilirubinaemia
## Footnote
These signs indicate increased RBC destruction and bilirubin production.
136
What infection causes infectious mononucleosis?
EBV infection
## Footnote
Epstein-Barr Virus (EBV) is responsible for this condition.
137
What symptoms are associated with infectious mononucleosis?
* Fever
* Pharyngitis
* Lymphadenopathy
## Footnote
These symptoms are common in patients with infectious mononucleosis.
138
How is infectious mononucleosis diagnosed?
Heterophile antibody test (Monospot), EBV serology
## Footnote
These tests help confirm the presence of EBV and related antibodies.
139
What is the function of Antithrombin?
Inhibits thrombin, Factor Xa
## Footnote
Antithrombin is a key natural anticoagulant that helps regulate blood clotting by inhibiting specific clotting factors.
140
What does Protein C degrade?
Factors Va, VIIIa
## Footnote
Protein C is activated in the presence of Protein S and plays a crucial role in the regulation of coagulation.
141
What is the role of Protein S?
Cofactor for Protein C
## Footnote
Protein S enhances the anticoagulant effects of Protein C.
142
What is the purpose of mixing studies in coagulation?
Differentiate factor deficiency from inhibitors
## Footnote
Mixing studies help identify whether a prolonged PT/aPTT is due to a deficiency of clotting factors or the presence of inhibitors.
143
What is the significance of Vitamin K in coagulation?
Essential for γ-carboxylation of Factors II, VII, IX, X
## Footnote
Vitamin K is crucial for the synthesis of certain clotting factors, and its deficiency can lead to bleeding disorders.
144
How is Vitamin K deficiency monitored?
Monitored via PT/INR
## Footnote
Prothrombin time (PT) and International Normalized Ratio (INR) are used to assess the coagulation status related to Vitamin K.
145
What does D-Dimer measurement detect?
Fibrin degradation products
## Footnote
D-Dimer is a useful marker in diagnosing thrombosis but can yield false positives in various conditions.
146
What is the sensitivity and specificity of D-Dimer for thrombosis?
High sensitivity, low specificity
## Footnote
While D-Dimer tests are sensitive for conditions like DVT and PE, they are not specific and can be elevated in other situations.
147
What does External Quality Assessment (EQA) ensure?
Lab result accuracy
## Footnote
EQA programs allow laboratories to benchmark their performance and maintain accreditation standards.
148
What is the structure of the red cell membrane?
Lipid bilayer with embedded proteins
## Footnote
The red cell membrane contains various proteins that play roles in transport and maintaining cell shape.
149
What are the cytoskeletal proteins that maintain red cell shape?
Spectrin, ankyrin
## Footnote
These proteins form a network that provides structural support to the red blood cell membrane.
150
What are the integral proteins important for transport in red blood cells?
Band 3, glycophorin
## Footnote
Integral proteins facilitate the movement of ions and molecules across the red cell membrane.
151
What is the principle of HPLC in the context of hemoglobin variants?
Separation of Hb fractions based on charge
## Footnote
High-Performance Liquid Chromatography (HPLC) is used to analyze and separate different hemoglobin variants.
152
What does capillary electrophoresis measure in hemoglobin variants?
Migration of Hb variants in electric field based on charge & size
## Footnote
This technique allows for the separation and identification of hemoglobin variants based on their physical properties.
153
What activates plasminogen to plasmin?
tPA/uPA
## Footnote
Tissue Plasminogen Activator (tPA) and urokinase Plasminogen Activator (uPA) are key in the fibrinolysis process.
154
What does plasmin do?
Degrades fibrin → fibrin degradation products
## Footnote
Plasmin is essential for breaking down fibrin clots, leading to the resolution of blood clots.
155
What inhibits plasmin?
PAI-1 and α2-antiplasmin
## Footnote
These inhibitors regulate the fibrinolysis process by preventing excessive degradation of fibrin.
