Page 305 - Textbook of Pathology, 6th Edition

1. Mean corpuscular volume (MCV) = Vitamin B (pyridoxine), vitamin E (tocopherol) and 289
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PCV in L/L riboflavin are the other essential vitamins required in the
_________________ synthesis of red cells.
RBC count/L
3. Amino acids. Amino acids comprise the globin compo-
The normal value is 85 ± 8 fl (77-93 fl)*. nent of haemoglobin. Severe amino acid deficiency due to

2. Mean corpuscular haemoglobin (MCH) = protein deprivation causes depressed red cell production.
4. Hormones. As discussed above, erythropoietin plays a
Hb/L
________________ significant regulatory role in the erythropoietic activity.
RBC count/L Besides erythropoietin, androgens and thyroxine also appear
The normal range is 29.5 ± 2.5 pg (27-32 pg)*. to be involved in the red cell production.
3. Mean corpuscular haemoglobin concentration HAEMOGLOBIN. Haemoglobin consists of a basic protein,
(MCHC) = globin, and the iron-porphyrin complex, haem. The molecular
weight of haemoglobin is 68,000. Normal adult haemoglobin
Hb/dl
_________________ (HbA) constitutes 96-98% of the total haemoglobin content
PCV in L/L and consists of four polypeptide chains, α β . Small quantities CHAPTER 12
2 2
The normal value is 32.5 ± 2.5 g/dl (30-35 g/dl). of 2 other haemoglobins present in adults are: HbF containing
α γ globin chains comprising 0.5-0.8% of total haemoglobin,
2 2
Since MCHC is independent of red cell count and size, it and HbA having α δ chains and constituting 1.5-3.2% of
2 2
2
is considered to be of greater clinical significance as compared total haemoglobin. Most of the haemoglobin (65%) is
to other absolute values. It is low in iron deficiency anaemia synthesised by the nucleated red cell precursors in the
but is usually normal in acrostic anaemia.
marrow, while the remainder (35%) is synthesised at the
RED CELL MEMBRANE. The red cell membrane is a reticulocyte stage.
trilaminar structure having a bimolecular lipid layer Synthesis of haem occurs largely in the mitochondria by
interposed between two layers of proteins. The important a series of biochemical reactions summarised in Fig. 12.7.
proteins in red cell membrane are band 3 protein (named on Coenzyme, pyridoxal-6-phosphate, derived from pyridoxine
the basis of the order in which it migrates during (vitamin B ) is essential for the synthesis of amino levulinic
6
electrophoresis), glycophorin and spectrin; important lipids acid (ALA) which is the first step in the biosynthesis of
are glycolipids, phospholipids and cholesterol; and protoporphyrin. The reaction is stimulated by erythropoietin
carbohydrates form skeleton of erythrocytes having a lattice- and inhibited by haem. Ultimately, protoporphyrin combines
like network which is attached to the internal surface of the with iron supplied from circulating transferrin to form haem.
membrane and is responsible for biconcave form of the Each molecule of haem combines with a globin chain
erythrocytes. synthesised by polyribosomes. A tetramer of 4 globin chains,
A number of inherited disorders of the red cell membrane each having its own haem group, constitutes the
and cytoskeletal components produce abnormalities of the haemoglobin molecule (Fig. 12.8, A).
shape such as: spherocytosis (spherical shape from loss of part RED CELL FUNCTIONS. The essential function of the red
of the membrane), ovalocytosis (oval shape from loss of cells is to carry oxygen from the lungs to the tissue and to
elasticity of cytoskeleton), echinocytosis (spiny processes from transport carbon dioxide to the lungs. In order to perform Introduction to Haematopoietic System and Disorders of Erythroid Series
external surface due to metabolic abnormalities of red cells), these functions, the red cells have the ability to generate
and stomatocytosis (bowl-shaped red cells from expansion of energy as ATP by anaerobic glycolytic pathway (Embden-
inner membrane on one side). Meyerhof pathway). This pathway also generates reducing
power as NADH and NADPH by the hexose monophosphate
NUTRITIONAL REQUIREMENTS FOR ERYTHRO- (HMP) shunt.
POIESIS. New red cells are being produced each day for
which the marrow requires certain essential substances. 1. Oxygen carrying. The normal adult haemoglobin, HbA,
These substances are as under: is an extremely efficient oxygen-carrier. The four units of
tetramer of haemoglobin molecule take up oxygen in
1. Metals. Iron is essential for red cell production because succession, which, in turn, results in stepwise rise in affinity
it forms part of the haem molecule in haemoglobin. Its
deficiency leads to iron deficiency anaemia. Cobalt and of haemoglobin for oxygen. This is responsible for the sigmoid
shape of the oxygen dissociation curve.
manganese are certain other metals required for red cell The oxygen affinity of haemoglobin is expressed in term
production.
of P value which is the oxygen tension (pO ) at which 50%
50
2
2. Vitamins. Vitamin B and folate are essential for bio- of the haemoglobin is saturated with oxygen. Pulmonary
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synthesis of nucleic acids. Deficiency of B or folate causes capillaries have high pO and, thus, there is virtual saturation
12
2
megaloblastic anaemia. Vitamin C (ascorbic acid) plays an of available oxygen-combining sites of haemoglobin. The
indirect role by facilitating the iron turnover in the body. tissue capillaries, however, have relatively low pO and, thus,
2
part of haemoglobin is in deoxy state. The extent to which
–1
*For conversions, the multiples used are as follows: ‘deci (d) = 10 , milli oxygen is released from haemoglobin at pO , in tissue
2
–6
–9
–3
(m) = 10 , micro (μ) = 10 , nano (n) = 10 , pico (p) = 10 –12 , femto (f) = capillaries depends upon 3 factors—the nature of globin
10 –15