WEEK 6 (Erythrocytes & other blood cells) Flashcards
Describe the process of the Bicarbonate Buffer system
CO2 enters cell plasma and erythrocytes -> Some CO2 dissolves in plasma, some binds to haemoglobin & some reacts with H2O to form H2CO3 (CARBONIC ACID) -> H2CO3 decomposes into HCO3- (BICARBONATE) AND H+ -> HCO3- moves into plasma down a conc gradient and Cl- enters erythrocytes -> H+ binds to haemoglobin in erythrocytes and plasma proteins in the plasma
How does the buffer system maintain pH balance?
LOW PH = H+ binds to HCO3- to form H2CO3
HIGH PH = H2CO3 dissociates into H+ and HCO3-
Where are red blood cells produced during embryonic development?
- EARLY WEEKS = yolk sac where RBCs are primitive & nucleated
- MIDDLE TRIMESTER = liver (main organ), spleen & lymph nodes
- LATE GESTATION/AFTER BIRTH = bone marrow
What are the stages of differentiation of Red blood cells?
1) PROERYTHROBLAST divides several times producing cells that begin to synthesise haemoglobin
2) Near the end of development, cell ejects its nucleus and becomes RETICULOCYTE
3) Passes from BONE MARROW into BLOODSTREAM
4) Reticulocytes develop into mature RBCs within 1-2 days after release from bone marrow
What is the role of cytokines in hematopoiesis?
Provide survival and proliferation signals
What is the function of ATP in RBCs?
- Energy production (only pathways supplying ATP to RBC)
- Reduction of methemoglobin
- 2,3 Bisphosphoglycerate binds to Hb (decreases its affinity for O2 and helps its availability to tissues)
Describe Pyruvate Kinase Deficiency
Pyruvate Kinase deficiency is the second most common genetic deficiency that causes HAEMOLYTIC ANAEMIA (occurs when you have a low number of red blood cells due to too much hemolysis in the body)
The red blood cell has NO MITOCHONDRIA and is totally dependent on anaerobic glycolysis for ATP. The decrease in ATP causes the ERYTHROCYTE to lose its BICONCAVE SHAPE & decreased ion pumping via Na+/K+ ATPase results in loss of ION BALANCE and causes OSMOTIC FRAGILITY leading to SWELLING and LYSIS
SYMPTOMS:
- Chronic haemolysis
- Increased 2,3-BPG resulting in lower-than-normal oxygen affinity of HbA
- Absence of Heinz bodies
Describe Familial 2,3-Bisphosphoglycerate deficiency
Familial 2,3-BPG deficiency causes CONGENITAL SECONDARY POLYCYTHEMIA and results from BISPHOSPHOGLYCERATEMUTASE deficiency. It causes a decrease in 2,3-BPG levels which causes the haemoglobin oxygen dissociation curve to the left.
EFFECTS:
- Increases haemoglobin affinity for oxygen -> decreased delivery of oxygen into peripheral tissues
- COMPENSATORY POLYCYTHEMIA due to release of erythropoietin
Describe Glucose-6-Phosphate Dehydrogenase deficiency
X-linked recessive metabolic disorder caused by deficient Glucose-6-Phosphate dehydrogenase which prevents the HMP pathway and thus the reduction of NADPH from NADP.
EFFECTS:
- Glutathione cannot be reduced -> cannot detoxify free radicals and peroxides
- Haemolytic anaemia due to poor RBC defines against oxidising agents
- Inflammatory response produces FREE RADICALS that diffuse into RBCs -> Oxidative damage
SYMPTOMS:
- Increased malarial resistance
- HEINZ BODIES
- BITE CELLS (Result from the Phagocytic removal of Heinz bodies by splenic macrophages)
Describe Pyrimidine 5’ Nucleotidase deficiency
An Autosomal Recessive disorder and the third most common enzymatic deficiency causing haemolysis. Pyrimidine 5’ Nucleotidase is required for RNA degradation in reticulocytes to remove residues of RNA -> deficiency causes BASOPHILIC STIPLING of RBCs
[Pyrimidine 5’ Nucleotidase activity is much higher in reticulocytes than mature red blood cells and is inhibited by lead]
SYMPTOMS:
- haemolytic anaemia
Describe Cytochrome b5 Reductase deficiency
NADH-cytochrome b5 reductase is the enzyme responsible for the conversion of METHEMOGLOBIN (Fe3+) to HAEMOGLOBIN (Fe2+). A deficiency of the enzyme causes the accumulation of methemoglobin which cannot bind oxygen.
SYMPTOMS:
- Chocolate cyanosis
- Chocolate-coloured blood
