Red cells haemorrhage and intro to anaemia

Question 1

basic structure and function of RBC’s

Answer 1

discoid, 7microm diameter
No nucleus or RNA
Shape allows: flexibility (can go through capillaries half their diameter) and increased area for gas exchange

Question 2

RBC function

Answer 2

Carry Hb

Allows gas exchange: carry oxygen form lung to tissues, carry CO2 tissues to lungs

Question 3

How is the RBC’s unique shape and deformability created? what can go wrong?

Answer 3

Determined by membrane (lipid bipolar layer) and cytoskeletal proteins (spectrin, actin, ankyrin)
Inherited abnormalities of said membrane proteins = shortened lifespan of red cells.. cell hemolysis (can’t pass through the filter membrane in the spleen so easily so are taken out of the circulation quicker)
Hereditary spherocytosis

Question 4

How does the RBC get energy?

Answer 4

No nuclei or mitochondria, but needs energy source to keep Hb in reduced state and maintain osmotic equilibrium
glycolytic pathways produce ATP - maintains osmotic equilibrium
HMP shunt produces NADPH - keeps Hb reduced
- Inherited defects in enzyme pathways
- GGDP deficiency, increased red cell hemolysis and turnover

Question 5

Haemoglobin carriage

Answer 5

2 alpha and 2 beta chains then haem group
Small amounts of HbF and HbA2
defective production of global chains = thalassemia
Deficiency of iron - reduced production of haem = low Hb

Question 6

Erythroid unit development

Answer 6

From myeloid multi lineage progenitor

• Erythroid burst forming unit earliest (BFU-E), respond to IL-3, GM-CSF and HIGH levels of EPO
• Erythroid colony forming units (CFU-E), more EPO receptors, respond LOW doses EPO

Question 7

Morphological stages

Answer 7

pronormoblast
Normoblast - early intermediate and late stages of development
Reticulocyte
Erythrocyte

Question 8

Kinetics of erythropoiesis

Answer 8

1 promormoblast –> 16 RBC’s
7-10 days, reticulocyte maturation 2 days
4 cell cycles/ divisions

Question 9

Erythroid changes with differentiation

Answer 9

Progressive increase in haemoglobin
Chromatin clumping
Extrude nucleus
Loss of RNA

Question 10

Significance of reticulocytes in the blood?

Answer 10

normally 1-2% of red cells, increased in blood loss hemolysis, low in cases of bone marrow failure

Question 11

Crticial requirements for red cell production

Answer 11

iron
folate
vitamin B12

Question 12

Regulation of erythrocytes

Answer 12

av RBC lifespan 120 days 
ERYTHROPOIETIN regulates 
- glycoprotein 
- Produced in the kidney 
- Production of EPO in response to low oxygen tensions

Question 13

Effects of EPO

Answer 13

Acts through specific EPO receptor to increase RBC production 
stimulation of BFU-E and CFU-E
inc hemoglobin synthysis 
Inc RBC maturation time 
Ince reticulocyte release 
Inc hemoglobin 
therefore inc Ox delivery

Question 14

new methods in doping testing

Answer 14

compare ratio of mature: immature RBC’s if nigh numbers of mature not accompanied by high numbers of immature, suggests RBC’s artificially introduced by transfusion, else must demonstrate through hemaotcrit + haemoglobin results over time

Question 15

EPO clinical implications

Answer 15

Renal failure patients, low Hb 
Clinical use of recombinant EPO
- anaemia of renal failure 
- other anemias 
- potential for abuse - sport

Question 16

How are RBC broken down?

Answer 16

If cells become less deformable removed in spleen
Break down of red cells with release of Hb, Hb broke into globing chains and haem
iron - transferrin - bone marrow
protoporphyrin - bilirubin - liver - bile

Question 17

Relative polycythemia

Answer 17

Alterations in total plasma volume also affect the haemoglobin concentrations e.g. if a person is dehydrated decrease plasma vol

Question 18

Anaemia definition

Answer 18

reduction in Hb conc in the blood <135g/l males and <115g/l females
neonates <140g/l, but this falls dramatically during the first few months of life
usually but not always accompanied by fall in red cell count and packed cell volume (PCV)
Alterations in total plasma volume also affect haemoglobin conc, dehydration may mask anaemia

Question 19

Clinical features of anaemia

Answer 19

Increased cardiac stroke volume, tachycardia, right shift in the Hb dissociation curve
Can be asymptomatic, patients will eventually develop shortness of breath, fatigue, pallor and finally congestive cardiac failure if severe enough, degree of symptoms experienced depends on speed of onset of anaemia
Hb dissociation curve shifts to the right, rise in 2,3 DPG levels, oxygen more readily available in tissues

Question 20

Reticulocyte counts

Answer 20

normally 0.5-2.5%, rises secondarily to increased EPO levels, after acute haemorrhage, reticulocyte count rises within 2-3 days and peaks at 6-10 days, remains raised until the haemoglobin returns to normal

Question 21

Factors that impair the normal reticulocyte response

Answer 21

Marrow disease 
Iron, vit B12 or folate deficincy 
Lack of EPO (renal disease) 
Ineffective erythropoiesis as in thalassemia and myelodysplastic syndromes 
chronic inflammation or malignancy

Question 22

How can the marrow be tested for iron store information?

Answer 22

Bone marrow examination may reveal the cause of anaemia, especially when abnormal white cell pop present
Marrow can be examined for fibrosis and stained for presence of iron in macrophages, Perls’ stain

Question 23

red cell reporting

Answer 23

Population in blood as hematocrit (HCT) or as concentration of haemoglobin (Hb)
HCT = fraction of blood by volume occupied by red blood cells,