DISORDERS OF RBCs

The disorders of RBCs can be grouped in two major categories;

 Quantitative deficiency
 Quantitative excess.

Let’s now study these disorders in detail.

QUANTITATIVE DEFICIENCY

These disorders are mainly due deficiency in the number of RBCs in blood. This condition is
also known as ANEAMIA. The cause is reduction in the population of RBCs in blood,
sometimes reduction in the level of haemoglobin can also be possible reason.

Signs and symptoms

ANEAMIA goes undetermined in many people and symptoms can be minor or vague. The
signs and symptoms can be related to the ANEAMIA itself, or the underlying cause.

Most common symptoms seen in people are;

I. Feeling of weakness, or fatigue, general malaise and sometimes poor concentration.

II. They may also report dyspnoea (shortness of breath) on exertion. In very severe ANEAMIA.
III. The patient may have symptoms such as palpitations, angina (if pre-existing heart disease is
present), intermittent claudication of the legs, and symptoms of heart failure.
IV. On examination, the signs exhibited may include pallor (pale skin, mucosal linings and nail
beds) but this is not a reliable sign. There may be signs of specific causes of ANEAMIA, e.g.,
koilonychia (in iron deficiency), jaundice (when ANEAMIA results from abnormal break down
of red blood cells — in haemolytic ANEAMIA), bone deformities (found in thalassaemia
major) or leg ulcers (seen in sickle cell disease).
V. In severe ANEAMIA, there may be signs of a hyper dynamic circulation: a fast heart rate
(tachycardia), flow murmurs, and cardiac enlargement. There may be signs of heart failure.
VI. Pica, the consumption of non-food based items such as dirt, paper, wax, grass, ice, and hair,
may be a symptom of iron deficiency, although it occurs often in those who have normal
levels of HAEMOGLOBIN.
VII. Chronic ANEAMIA may result in behavioural disturbances in children as a direct result of
impaired neurological development in infants, and reduced scholastic performance in
children of school age.
VIII. Restless legs syndrome is more common in those with iron deficiency ANEAMIA.

CLASSIFICATION

In morphological approach, ANEAMIA is classified by the size of red blood cells; this is either
done automatically or on microscopic examination of a peripheral blood smear. The size is
reflected in the mean corpuscular volume (MCV).

I. If the cells are smaller than normal (under 80 fl), the ANEAMIA is said to be Microcytic.
 II. If they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100
fl), the ANEAMIA is classified as Macrocytic.
III. If the overall HAEMOGLOBIN levels are decreased, but the red blood cell size (Mean
corpuscular volume) remains normal, the ANEAMIA is said to be Normocytic.

I. MICROCYTIC ANEAMIA: Microcytic ANEAMIA is primarily a result of HAEMOGLOBIN

synthesis failure/insufficiency, which could be caused by several etiologies;
1. Deficiency in HEME synthesis process which can be caused by
a) IRON DEFICIENCY.
b) ANEAMIA OF CHRONIC DISEASE (COMMONLY KNOWN AS
MORMOCYTIC ANEAMIA).

2. GLOBIN synthesis defect, which can be due to

a) THALLESIMIA.
b) Various other unstable haemoglobin diseases.

3. SIDEROBLASTIC DEFECTS: Caused by abnormal production of ringed

sideroblasts, it can be;
a) HEREDITARY.
b) Acquired due to LEAD TOXICITY.
II. MACROCYTIC ANEAMIA: Megaloblastic ANEAMIA, the most common cause of
macrocytic ANEAMIA, is due to a deficiency of either vitamin B12, folic acid (or both).
Deficiency can be either due to inadequate intake or insufficient absorption. Macrocytic
ANEAMIA can be further divided into "megaloblastic ANEAMIA" or "non-megaloblastic
macrocytic ANEAMIA". The cause of megaloblastic ANEAMIA is primarily a failure of
DNA synthesis with preserved RNA synthesis, which results in restricted cell division of
the progenitor cells. The megaloblastic ANEAMIA is often present with neutrophil hyper
segmentation (6–10 lobes). The non-megaloblastic macrocytic ANEAMIA has different
etiologies (i.e. there is unimpaired DNA globin synthesis,) which occur, for example in
alcoholism.
III. NORMOCYTIC ANEAMIA: Normocytic ANEAMIA occurs when the overall HAEMOGLOBIN
levels are always decreased, but the red blood cell size (Mean corpuscular volume)
remains normal. Causes include:
a) Acute blood loss.
b) ANEAMIA of chronic disease.
c) Aplastic ANEAMIA (bone marrow failure).
d) Haemolytic ANEAMIA.

APLASTIC ANEAMIA

It is a condition where bone marrow does not produce sufficient new cells to replenish blood
cells. The condition, per its name, involves both aplasia and ANEAMIA. Typically, ANEAMIA
refers to low red blood cell counts, but aplastic ANEAMIA patients have lower counts of all
three blood cell types: red blood cells, white blood cells, and platelets, termed pancytopenia.

CAUSES
 In many cases, the reason is considered to be idiopathic (cannot be determined), but one
known cause is an autoimmune disorder in which white blood cells attack the bone marrow.
 It is also sometimes associated with exposure to toxins such as benzene, or with the use of
certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine,
and phenylbutazone.
 Exposure to ionizing radiation from radioactive materials or radiation-producing devices is
also associated with the development of aplastic ANEAMIA.
 Aplastic ANEAMIA is present in up to 2% of patients with acute viral hepatitis.

MEGALOBLASTIC ANEAMIA

This results from inhibition of DNA synthesis in red blood cell production. This is often due to
deficiency of vitamin B12 and/or folic acid. Vitamin B12 deficiency alone will not cause the
syndrome in the presence of sufficient folate, for the mechanism is loss of B 12 dependent
folate recycling, followed by folate-deficiency loss of nucleic acid synthesis (specifically
thymine), leading to defects in DNA synthesis. When DNA synthesis is impaired, the cell cycle
cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing
cell growth without division, which presents as macrocytosis.

Megaloblastic ANEAMIA not due to hypo-vitaminosis may be caused by anti-metabolites

that poison DNA production directly, such as some chemotherapeutic or antimicrobial
agents (for example azathioprine or trimethoprim). It is characterized by many large
immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by
hypersegmented or multisegmented neutrophils.

CAUSES

 Vitamin B12 deficiency, it can be due to malabsorption, deficient intake.

 Folate deficiency can be due to alcoholism, deficient intake, during increased need such as
pregnancy, infant, rapid cellular proliferation, and cirrhosis.

 Due to malbsorption.

 Inherent synthesis disorders of and Pyrimidines (ORITIC ACIDURIA).

 Combined deficiency of Vit. B12 and Folate.

 Inherent DNA synthesis disorder

HEINZ-BODY ANEAMIA

Heinz bodies form in the cytoplasm of RBCs and appear like small dark dots under the
microscope. There are many causes of Heinz body ANEAMIA, and some forms can be drug
induced. It is triggered in cats by eating onions or acetaminophen (paracetamol). It can be
triggered in dogs by ingesting onions or zinc, and in horses by ingesting dry red maple
leaves.
 REFRACTORY ANEAMIA

Refractory ANEAMIA is an ANEAMIA which does not respond to treatment. It is often seen
secondary to myelodysplastic syndromes.

Iron deficiency ANEAMIA may also be refractory as a clinical manifestation of

gastrointestinal problems which disrupt iron metabolism.

QUANTITATIVE EXCESS

These diseases are caused due to increase in the level of the RBCs in the blood; these
conditions arise either due to increased production of RBCs or a misbalance between
production and destruction of the cells. The disease is generally called POLYCYTHEMIA; the
patients have a high Hematocrit value, HAEMOGLOBIN count, or Red-blood cell count.

TYPES

PIRMARY POLYCYTHEMIA: Primary polycythemias are due to factors intrinsic to red cell
precursors. Polycythemia Vera (PCV), Polycythemia rubera Vera (PRV), or erythraemia,
occurs when excess red blood cells are produced as a result of an abnormality of the bone
marrow. Often, excess white blood cells and platelets are also produced.

Polycythemia Vera is classified as a myeloproliferative disease. Symptoms include headaches

and vertigo. Signs on physical examination include an abnormally enlarged spleen and/or
liver. In some cases, affected individuals may have associated conditions including high
blood pressure or the formation of blood clots. Transformation to acute leukaemia is rare.

Primary familial polycythemia, Primary familial and congenital polycythemia (PFCP) also
exists as a benign hereditary condition, in contrast with malignant acquired Polycythemia
Vera. In some of the cases a molecular mechanism of PFCP has been identified to be a
dominant mutation in the erythropoietin receptor.

SECONDARY POLYCYTHEMIA

Secondary polycythemia is usually due to increased erythropoietin production either in

response to chronic hypoxia (low blood oxygen level) or from an erythropoietin secreting
tumour. In secondary polycythemia, there may be 6 to 8 million and occasionally 9 million
erythrocytes per cubic millimetre of blood. Conditions which may result in a physiologically
appropriate polycythemia include:

 Altitude related - This physiologic polycythemia is a normal adaptation to living at high

altitudes; athletes train at high altitude to take advantage of this effect — a legal form of
blood doping.
 Hypoxic disease associated - For example in cyanotic heart disease where blood oxygen
levels are reduced significantly. May also occur as a result of hypoxic lung disease and as a
result of chronic obstructive sleep apnoea.

 Iatrogenic - Secondary polycythemia can be induced directly by phlebotomy (blood letting)

to withdraw some blood, concentrate the erythrocytes, and return them to the body.

 Genetic - Heritable causes of secondary polycythemia also exist and are associated with
abnormalities in HAEMOGLOBIN oxygen release. Patients have a special form of
HAEMOGLOBIN known as Hb Chesapeake, which has a greater inherent affinity for oxygen
than normal adult HAEMOGLOBIN. This reduces oxygen delivery to the kidneys, causing
increased erythropoietin production and a resultant polycythemia.

Conditions where the polycythemia is not as a result of physiologic adaptation and occurs
irrespective of body needs include:

 Neoplasms - People with testosterone levels high because of the use anabolic steroids,
including athletes who abuse steroids and patients on high doses of steroids, as well as
people who take erythropoietin may develop secondary polycythemia.

RELATIVE POLCYTHEMIA

 In some forms of secondary polycythemia, the HAEMOGLOBIN or red blood cell count is
perceived to be abnormally high due to an increased concentration of blood. This can
happen as a result of plasma volume loss from dehydration, severe vomiting or diarrhoea, or
excessive sweating. Polycythemia in these situations may be called relative polycythemia,
because the actual numbers of red blood cells are not abnormal.

STRESS POLYCYTHEMIA

 Stress polycythemia is a term applied to a chronic state of low plasma volume which is seen
commonly in active, hard working, anxious, middle-aged men. In these people, the red blood
cell volume is normal, but the plasma volume is low. This condition is also known as
Gaisbock's disease, stress erythrocytosis, or pseudopolycythemia.

 Smoker's polycythemia is a similar condition in which increased levels of deoxygenated

HAEMOGLOBIN causes an increase in red blood cell counts