PBL Topic 2 Case 7 Flashcards
Explain how haemoglobin is involved in the return of CO2 to the lungs
- Contains carbonic anhydrase
- Allows CO2 to react with H2O
- To form bicarbonate ions
What does mean corpuscular volume measure?
- Size of red blood cells
What is the normal range of the mean corpuscular volume?
- 80 - 99 femtolitres (fL)
What is the mean diameter, thickness and volume of red blood cells?
- Diameter: 7.8 uM
- Thickness: 2.5 uM
- Volume: 90-95 cubic uM
How does the average number of red blood cells differ in males and females?
- Males: 5,200,000
- Females: 4,700,000
What is meant by the term hematocrit?
- Percentage of blood composed of red blood cells
What is the normal value of hematocrit?
- 45 per cent
Where are red blood cells produced in early embryonic life?
- Yolk sac
Where are red blood cells produced during the second trimester?
- Liver
- Spleen
- Lymph Nodes
Where are red blood cells produced during the final month of gestation and after birth?
- Bone marrow
In which types of bones does the marrow typically produce red blood cells after birth?
- Membraneous bones
- Including sternum, ribs and vertebrae
What is a pluripotential haematopoietic stem cell?
- Type of cell from which all cells of the circulating blood are derived
What is a committed stem cell?
- Type of cell that differentiates to form other types of cell
What is a CFU-E?
- Colony-Forming-Unit Erythrocyte
- A committed stem cell that produces erythrocytes
What is a CFU-GM?
- Colony-Forming-Unit Granulocyte and Monocyte
- A committed stem cell that produces granulocytes and monocytes
Identify factors that affect the formation of growth and differentiation inducers in erythrocytes
- Exposure to low oxygen in the blood
Identify factors that affect the formation of growth and differentiation inducers in lymphocytes
- Exposure to a pathogen in the blood
What is CFU-M?
- Colony-Forming-Unit Megakaryocyte
- A committed stem cell that produces platelets
What is the role of erythropoietin?
- Stimulates proliferation of erythrocyte progenitor cells
- Stimulates their differentiation in mature erythrocytes
What is the role of thrombopoeitin?
- Stimulating of megakaryocyte production
- Via its c-mpl receptor
Identify the roles of 3 different colony stimulating factors
- GM-CSF: Increases stem cell commitment to granulocyte and monocyte production
- G-CSF: Increases stem cell commitment to granulocyte production
- M-CSF: Increases stem cell commitment to monocyte production
Identify the roles of IL-3, IL-5 and IL-11
- IL-3: Growth and reproduction of all types of stem cells
- IL-5: Growth and differentiation of eosinophils
- IL-11: Promotes megakaryocyte production
Identify the role of Stem Cell Factor
- Synergises with IL-3 and GM-CSF
- To increase proliferation of many types of stem cells
Identify the six generations of erythrocytes
- Proerythroblast
- Basophil Erythroblast
- Polychromatophil Erythroblast
- Orthochromatic Erythroblast
- Reticulocyte
- Erythrocyte
What occurs during the successive stages of red cell differentiation?
- Accumulation of haemoglobin (B)
- Nucleus is absorbed (B)
- Endoplasmic reticulum is absorbed (B)
- Passage from the bone into the capillaries by diapedesis (R)
Where is erythropoietin produced?
- Kidneys
Explain how erythropoietin stimulates erythropoietic activity?
- Under hypoxic conditions
- Binds to Hypoxia Inducible Factor
- Which binds to Hypoxia Response Element
- Activates gene transcription
- Via the combined effects of nuclear factor and co-activator p300
- Increased proportion of committed cells to erythropoiesis
- Stimulation and differentiation of CFU-E
Explain how under normal conditions HIF is controlled
- The HIF-alpha subunit is hydroxylated
- Which promotes interaction with von Hippel-Lindau E3 ubiquitin ligase
- Resulting in degradation of HIF
What is the lifespan of an erythrocyte?
- 120 days
Identify five roles of the cytoplasmic enzymes contained within erythrocytes
- Glucose metabolism
- Maintain pliability
- Membrane transport
- Maintain ferrous iron
- Prevents oxidation of proteins
What is the role of Kupffer cells?
- Types of macrophages produce by the liver
- Phagocytosis of haemoglobin from worn out red blood cells
What is the role of Transferrin?
- Transport of iron from the haemoglobin from worn out red blood cells to the bone marrow
- For either production of new red blood cells or storage as ferritin
What happens to the porphyrin portion of the haemoglobin of worn out red blood cells?
- Converted into bilirubin my macrophages
- Removed from the body by secretion through the liver into the bile
Explain how red blood cells may self-destruct in the spleen
- Squeeze through red pulp into the trabeculae
Explain how a molecule of pyrrole is produced in the formation of Haemoglobin
- Succinyl coenzyme A is formed in the Krebs cycle
- It binds with glycine to form Pyrrole
Explain how protoporphyrin IX is produced in the formation of Haemoglobin
- Four molecules of pyrrole combine
Explain how haem is formed formed protoporphyrin IX
- Protoporphyrin IX reacts with ferrous iron (Fe2+)
Explain how a haemoglobin chain is produced from haem
- Haem combines with globulin
Which chains make up Haemoglobin A?
- 2 x Alpha Chain
- 2 x Beta Chain
How many molecules of oxygen can be transported by a molecule of haemoglobin? Why is this the case?
- Four
- There are four haem group
- Which contain a single iron atom
- That can form a loose bond with oxygen
How does the T conformation of haemoglobin differ to the R conformation?
- T: Globin chains are held tight together
- R: Oxygen binding sites are more exposed
- Therefore R conformation has a higher affinity for oxygen
Why is haemoglobin considered an allosteric protein
- Binding of one oxygen molecule increases oxygen affinity of the remaining binding sites
- This explains the sigmoid shape of the oxygen dissociation curve
What is the effect of binding of hydrogen ions and carbon dioxide to haemoglobin?
- Reduced affinity for oxygen
- Bohr Effect
- Oxygen dissociation curve shifts right and downwards
What is the effect of oxygenation on haemoglobin?
- Reduced affinity for Carbon Dioxide
- Haldane Effect
What is the effect of 2,3-BPG on haemoglobin?
- Stabilises T-conformation
- Reduced affinity for oxygen
- Oxygen dissociation curve shifts right and downwards
Explain the role of ferrireductase
- Conversion of ferric iron (Fe3+) to ferrous iron (Fe2+)
Explain the role of DMT1 (Divalent Metal Transporter)
- Divalent Metal Transporter
- Transports iron across the luminal surface of the mucosal cells in the small intestine
Explain the role of HCP1
- Haem Carrier Protein 1
- Transports haem across the luminal surface of the mucosal cells in the small intestine
Explain the role of FPN-1
- Ferroportin 1
- Transports iron out of mucosal cell
- Requires hephaestin
Explain the role of Hepcidin
- Regulation of iron absorption
- By binding to iron-exporting protein Ferroportin 1
- Causing its degradation
- Decreasing iron efflux
What is the role of apotransferrin
- Combines with iron to form transferrin
- Which is transported in the plasma
Identify two locations where iron is deposited
- Liver
- Bone Marrow
Explain how haemoglobin is produced from circulating iron
- Transferrin attaches to surface receptor on erythrocyte
- Iron is released and transported to mitochondria
- Iron combines with protoporphyrin to form haem
Explain how iron is stored from circulating iron
- Transferrin attaches to surface receptor on erythrocyte
- Iron combine with apoferritin to form ferritin
How does ferritin differ from hemosiderin
- Ferritin is soluble
- Hemosiderin is insoluble
Identify three causes of iron deficiency
- Blood loss, typically from GI tract
- Demands of growth and pregnancy
- Decreased absorption
- Poor intake
Identify the four generations of granulocytes
- Myeloblast
- Promyelocyte
- Myelocyte
- Metamyelocyte
What are band forms?
- Immediate precursor of mature granulocytes
- With irregular horseshoe shaped nucleus
What is the difference between left and right shift?
- Left shift involves mobilisation of metamyelocytes
- Right shift involves further maturation
Identify five locations in which lymphocytes and plasma cells are produced
- Bone marrow
- Spleen
- Thymus
- Lymph Glands
- Peyer’s Patches underneath epithelium in gut wall
What is anaemia?
- Reduction in haemoglobin
- Below the reference level for the age and gender of the individual
Identify three types of anaemia, how are they classified?
- Microcytic Anaemia
- Normocytic Anaemia
- Macrocytic Anaemia
- Classified based on MCV
Identify two mechanisms that occur, resulting in an asymptomatic patient of anaemia
- Enhancement of oxygen carrying capacity of blood
- Rise in 2,3-BPG allowing for oxygen dissociation at the tissues
Identify 7 general symptoms of anaemia
- Fatigue
- Headache
- Faintness
- Breathlessness
- Angina
- Claudication
- Palpitations
What is claudication?
- Pain in limb
- That occurs on exercise
- Due to obstruction of an artery
Identify 7 signs of anaemia
- Pallor
- Tachycardia
- Systolic Flow Murmur
- Koilonychia (spoon shaped nails)
- Jaundice
- Bone deformities
- Leg ulcers
How can exercise be used to assess the effects of anaemia?
- Exercise causes angina and intermittent claudication
Identify five evaluation tools when a patient presents with a low haemoglobin count
- Red blood cell indices
- White blood cell count
- Platelet count
- Reticulocyte count (as this indicates marrow activity)
- Blood film
What is meant by the term dimorphic and when may this be seen on a blood film?
- Two populations of red cells are seen
- In patients with double deficiencies
- For example iron and folate deficiency in coeliac disease
What is meant by the term poikilocytosis?
- Variation in cell shape
- As demonstrated in microcytic anaemia
What is mean by the term anisocytosis?
- Variation in cell size
- As demonstrated in microcytic anaemia
Identify two methods of obtaining and examining bone marrow
- Aspiration provides a film which can be examined by microscopy
- Trephine provides a core of bone which is processed on a histological specimen