Anaemia and polycythaemia

Blood Physiology Lecture Two

Ass.Professor Dr. Samer Al Hakkak

Dean College Of Medicine/University of Alkafeel
PhD ( General Surgeon), FRCS ( Ireland), FACS, MRCS (England, Glasgow,
Edinburgh, Ireland)

March 2024
 Learning objectives

By the end of this session, the students able to:

 Define anaemia and identify types and causes

 Know the clinical features of anaemia.
 Recognize polycythaemia and types and causes
 Illustrate the clinical features of polycythaemia.

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 ANAEMIA

Anaemia means deficiency of haemoglobin in the blood, which can be caused by either too
few RBCs or too little haemoglobin in the cells

The WHO defines anaemia in

adults as a hemoglobin less than 130 g/L
(13 g/dL) in Males, and less than 120 g/L
(12 g/dL) in Females.

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 Question poll 1 :

A 20-year-old female presented to the outpatient clinic with pallor, easy fatigability CBC
did (Hb % level show report ) what is the diagnosis?

Complete blood count CBC normal value

Hb % 10 g/dl (12-15 g/dl)
WBC 12000 ( 4000- 11000) per microliter
Platelets 140,000 (150,000-400,000 )per microliter

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 Types of anaemia:

 1- Iron deficiency anaemia (due to blood loss, either acute or chronic) diet, absorption,
demand

 2- Megaloblastic Anaemia. (Vitamin B12, folic acid, and intrinsic factor)

 3- Hemolytic Anaemia (red cell destruction )

 4- Aplastic anaemia due to bone marrow dysfunction.(Bone marrow aplasia means lack
of functioning bone marrow)

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 1- Iron deficiency anemia

A- Acute blood loss:

It is not immediately apparent because the total blood volume is reduced. After rapid
haemorrhage, the body replaces the fluid portion of the plasma in 1 to 3 days, but this
response results in a low concentration of RBCs. If a second haemorrhage does not occur,
RBC concentration usually returns to normal within 3 to 6 weeks.
B- Chronic blood loss:
Chronic blood loss occurs when a person frequently cannot absorb enough iron from the
intestines to form haemoglobin as rapidly as it is lost. RBCs that are much smaller than
normal and have too little haemoglobin inside them are then produced, and dietary
deficiency of iron also pregnancy, giving rise to microcytic, hypochromic anaemia (Figure 1
& 2)

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Hypochromic iron deficiency anaemia

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 Question poll

The characteristic feature of IDA is

A. Hypochromic anaemia
B. Hypochromic macrocystic anaemia
C. Normochromic microcystic anaemia
D. Hypochromic microcystic anaemia
E. Hyperchromic microcytic anaemia

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 2.Megaloblastic Anaemia.

 Vitamin B12, folic acid, intrinsic factors(dietary or absorption) from the stomach mucosa,
and loss of any of these can lead to slow reproducing erythroblasts in the bone marrow.

 As a result, the RBCs grow too large, with odd shapes, and are called megaloblasts
erythroblasts in the bone marrow show a characteristic abnormality – maturation of the
nucleus being delayed relative to that of the cytoplasm.

 The underlying defect accounting for the asynchronous maturation of the nucleus is
defective DNA synthesis, usually caused by a deficiency of vitamin B12 or folate.

 Thus, atrophy of the stomach mucosa, as occurs in pernicious anaemia or loss of the
entire stomach after surgical total gastrectomy, can lead to megaloblastic anaemia.

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 Also, megaloblastic anaemia often develops in patients who have intestinal sprue, in
which folic acid, vitamin B12, and other vitamin B compounds are poorly absorbed.

 Because in these states, the erythroblasts cannot proliferate rapidly enough to form
normal numbers of RBCs,

 The formed RBCs are mostly oversized, have bizarre shapes, and have fragile membranes.
 These cells rupture easily, leaving the person in dire need of adequate RBCs.

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 3- Hemolytic anaemia.

 Anaemia results from an increase in the rate of red cell destruction.

 Different abnormalities of the RBCs, many of which are hereditary, or acquired, make the
cells fragile, so they rupture easily as they go through the capillaries, especially through
the spleen.
 Hereditary hemolytic anaemia can result from (membrane defects, defective red cell
metabolism or abnormal Hb).
 Even though the number of RBCs formed may be normal or even much greater than
normal in some
 In hemolytic diseases, the life span of the fragile RBC is so short that the cells are
destroyed faster than they can be formed, and serious anemia results.

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 Life span

Why the life span of RBC is 120 days?

Human red blood cells are formed mainly in the bone marrow and are believed to have an
average lifespan of approximately 120 days after which they are replaced.
Because they wear out so quickly, an entire supply of red blood cells is renewed every four
months.

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 Some examples of hereditary hemolytic anaemias:

A. Hereditary spherocytosis HS (Membrane defect): caused by defects in the proteins

 involved in the vertical interactions between the membrane skeleton and the lipid bilayer
of the red cell.
 The RBCs are very small and spherical rather than being biconcave disks.
 These cells cannot withstand compression forces because they lack the normal loose,
baglike cell membrane structure of biconcave disks.
 Upon passing through the splenic pulp and some other tight vascular beds, they are
easily ruptured by even slight compression.

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 Hereditary spherocytosis figure

Hereditary spherocytosis. The peripheral blood smear shows many erythrocytes

with decreased diameter, intense staining, and no central pallor ( spherocytes).

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B. Sickle cell anaemia (Hb abnormality)
 It presents in 0.3 to 1.0 per cent of West African and American blacks,
 The cells have an abnormal type of haemoglobin called haemoglobin S containing faulty
beta chains in the haemoglobin molecule.
 It results from the inheritance of sickle β globin gene caused by substitution of valine for
glutamic acid in position 6 in the β-chain.
 When exposed to low oxygen concentrations, this haemoglobin precipitates into long
crystals inside the RBC. These crystals elongate the cell and give it the appearance of a
sickle rather than a biconcave disk.
 The precipitated haemoglobin also damages the cell membrane, so the cells become
highly fragile, leading to serious anaemia

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Sickle cell anaemia

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 Such patients frequently experience a vicious circle of events called a sickle cell disease
“crisis,” in which low oxygen tension in the tissues causes sickling, which leads to
ruptured RBCs, which causes a further decrease in oxygen tension and still more sickling
and RBC destruction.
 Once the process starts, it progresses rapidly, eventuating in a serious decrease in RBCs
within a few hours and, in some cases, death

Sickle cell anaemia.

Sickled cells ( straight arrows ) are evident.

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 C. G6PD deficiency (Defective Red cell metabolism)
 Deficiency in the glocuse-6-phospahate dehydrogenase enzyme that functions to reduce
nicotinamide adenine dinucleotide phosphate (NADP).

 It is the only source of NADPH which is needed for the production of reduced
glutathione; a deficiency renders the red cell susceptible to oxidant stress (drugs, fava
beans..etc)

 It inherited as sex‐linked, affecting males, and carried by females.

 The subject of RBCs to oxidant stress causes damaging of RBC membrane and denaturing
of Hb leading to hemolytic anaemia.

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G6PD deficiency map

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 An examples of acquired hemolytic anaemias:
Hemolytic disease of newborn (HDN) or erythroblastosis fetalis
 Rh-positive RBCs in the fetus are attacked by antibodies from an Rh-negative mother .
 These antibodies make the Rh-positive cells fragile, leading to rapid rupture and causing
the child to be born with a serious case of anaemia.
 The extremely rapid formation of new RBCs to make up for the destroyed cells in
erythroblastosis fetalis causes a large number of early blast forms of RBCs to be released
from the bone marrow into the blood.
 HDN due to ABO incompatibility
is usually MILD

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 4- Aplastic Anaemia Due to Bone Marrow Dysfunction.

 Bone marrow aplasia means lack of functioning bone marrow.

 For instance, exposure to high-dose radiation or chemotherapy for cancer treatment can
damage stem cells of the bone marrow, followed in a few weeks by anaemia.
 Likewise, high doses of certain toxic chemicals, such as insecticides or benzene in
gasoline, may cause the same effect.
 In autoimmune disorders, such as lupus erythematosus, the immune system begins
attacking healthy cells such as bone marrow stem cells, which may lead to aplastic
anaemia. In about half of aplastic anaemia cases the cause is unknown, a condition called
idiopathic aplastic
 anaemia people with severe aplastic anaemia usually die unless they are treated

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 Clinical Features of Anemia
The symptoms depend on four main factors:
 Speed of onset of anemia: Rapidly progressive anemia causes more
symptoms than that of gradual onset. This is because there is less time for
adaptation in the cardiovascular system.
 Severity of anemia: Mild anemia produces no symptoms compared to
significant symptoms in severe anemia.
 Age of the patient: Young patients can tolerate anemia better than elderly.
 Underlying illness:
The disease which caused
the anemia.

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 Clinical features of anaemia

In anemia, the lowered oxygen content of the circulating blood leads to tissue hypoxia.
General clinical features are either due to tissue hypoxia or compensatory mechanisms.
1. Due to tissue hypoxia:
• Nonspecific symptoms: Weakness, malaise and easy fatigability due to hypoxia of muscles.
• Dyspnea on mild exertion: It is due to the lowered oxygen content of the circulating blood.
• Pallor: Patients appear pale due to deficiency of red colored hemoglobin which is better
appreciated in the conjunctiva, mucous membrane of tongue and nail beds. Pallor associated
with icterus is suggestive of a hemolytic anemia.
• CNS: Patients of severe anemia may complain of headache, vertigo, tinnitus and lack of
concentration.

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 Clinical features of anaemia

2. Due to compensatory mechanisms:

• Cardiac features: Dyspnea on mild exertion, palpitation, tachycardia and cardiac murmur
occur
due to compensatory mechanisms.
The resulting increase in the cardiac output may cause congestive cardiac failure.

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 Polycythaemia

 Polycythaemia is defined as an increase in the haemoglobin concentration above the upper limit of
normal for the patient’s age and sex

 It can be classified according to the pathophysiology into two subdivisions: absolute polycythaemia
and relative or pseudopolycythaemia

 1- Absolute polycythaemia
A- Primary polycythaemia or polycythaemia vera
B- Secondary Polycythaemia
 2- Relative or pseudopolycythaemia:
In which the red cell volume is normal but the plasma volume is reduced.

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 A- Primary polycythaemia or polycythaemia vera

 The RBC count may be 7 to 8 million/mm3 and the hematocrit may be 60 to 70 percent instead of the
normal 40 to 45 percent.

 Polycythaemia Vera is caused by a genetic aberration (JAK2 mutation) in the haematopoietic stem cell
(HSC) cells that produce the blood cells.

 The blast cells no longer stop producing RBCs when too many cells are already present.

 This causes excess production of RBCs in the same manner that a breast tumor causes excess production
of a specific type of breast cell.

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 B-Secondary Polycythaemia.

 Whenever the tissues become hypoxic because of too little oxygen in the breathed air,
such as at high altitudes, or because of failure of oxygen delivery to the tissues, such as in
cardiac failure, the blood-forming organs automatically produce large quantities of extra
RBCs.
 This condition is called secondary polycythaemia, and the RBC count commonly rises to
6 to7 million/mm3 , about 30 percent above normal.
 A common type of secondary polycythaemia, called physiological polycythaemia, occurs
in natives who live at altitudes of 14,000 to 17,000 feet, where the atmospheric oxygen is
very low.
 The blood count is generally 6 to7 million/mm3 ; this blood count allows these people to
perform reasonably high levels of continuous work even in a rarefied atmosphere.

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 Clinical Features

 Most symptoms are due to the increased red cell mass and hematocrit.

 • Plethora (a morbid condition due to excess of RBCs in the blood or increase in the
quantity of blood) and cyanosis due to stagnation and deoxygenation of blood in
peripheral vessels are early findings. Headache, dizziness and visual problems result
from vascular disturbances in the brain and retina.
 • The elevated hematocrit results in increased blood viscosity and sludging. These
factors, along with thrombocytosis and abnormal platelet function, predispose to
thrombotic episodes.

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 By the end of the lecture………

Thank you for your attention

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 References:
 1- Guyton and Hall Textbook of Medical Physiology, 14th Edition, 2021
 2- Hoffbrand’s essential haematolgy, 8 th edition, 2018.
 3- Human anatomy and physiology.
 4- Essential in hematology and clinical pathology.

Question and answers?

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Homework
A B C D

E Email :info@alkafeel.edu.iq
F Website :http://Alkafeel.edu.iq
G H