2. Outline…
1) Structure of RBCs
2) Normal counts and variations
3) Functions of RBCs
4) Formation of RBCs and requirements
5) Variations in size of RBCs
6) Fate of aged RBCs
7) Packed cell volume and ESR
8) Anemia and polycythemia
9) Review questions
3. Objectives…
By the end of the lecture, learners should be able
to;
i. State the normal RBC count
ii. Identify an RBC
iii. Distinguish between PCV and ESR
iv. Outline the RBC indices and calculate them
v. Explain the fate of aged RBCs
vi. Distinguish between polycythemia and anemia
vii. Explain how anemia affects the CVS
viii.Elaborate the usefulness of regulating RBC
count
4. What are RBCs?
• Red blood cell are non-nucleated formed
elements in the blood.
• RBCs are also known as erythrocytes (erythros =
red).
• Red color of RBC is due to the presence of the
coloring pigment;- hemoglobin.
• RBCs, are the most abundant type of blood cell.
• About 2-3million new erythrocytes are produced
per second.
5. Normal counts and longevity
• Normal count varies with sex, males>females
• Avg is 5million cells/mm3 of blood
• Circulate for abt 100–120 days in the body
before their components are recycled
by macrophages.
• Take an avg of 20 seconds to complete one
cycle of circulation
• Cover about 700 miles in the 120 days
• Count of RBCs can increase or decrease as per
health conditions
6. Structure of RBC
• Mature RBCs are oval
biconcave disks and flexible.
• Each RBC is abt 7.8µm in
diameter and abt 2µm thick
at ends
• Lacks a cell nucleus and
most organelles ;-
accommodates maximum
space for Hb
• Membrane is elastic. why?
7. Is the biconcave shape of RBC
useful?
1) Allows equal and rapid diffusion of oxygen and
other substances into the interior of the cell.
2) Large surface area is provided for absorption or
removal of different substances.
3) Minimal tension is offered on the membrane when
the volume of cell alters.
4) RBCs squeeze through the minute capillaries very
easily without getting damaged.
8. How useful are RBCs?
RBCs serve the following functions;-
1. Mainly transports Hb, which in turn transports
respiratory gases (O2 and CO2)
2. Hb is a useful intracellular acid-base buffer
3. Blood group determination (carry antigen)
9. Fate of Old RBCs…
• After abt 120 days, RBC membrane is weak
• Old RBCs are immediately phagocytized by
macrophages of the body, particularly macrophages
present in liver (Kupffer cells), spleen and bone
marrow.
• The spleen (red pulp) is called ‘graveyard of RBCs’.
• Hb is degraded into iron, globin and porphyrin.
• Iron is stored in the body and reused later.
• Globin enters the protein depot for later use.
• Porphyrin is degraded into bilirubin; excreted by liver through
bile.
10. Variation is size of RBCs
• Under physiological conditions, the size of
RBCs in venous blood is slightly larger than
those in arterial blood.
• In pathological conditions, the variations in
size of RBCs are:
1. Microcytes (smaller cells)
2. Macrocytes (larger cells)
3. Anisocytes (cells with different sizes)
11. Variations in shape
• Shape of RBCs is altered in many conditions including
different types of anemia.
1. Crenation: Shrinkage as in hypertonic conditions.
2. Spherocytosis: Globular form as in hypotonic
conditions.
3. Elliptocytosis: Elliptical shape as in certain types of
anemia.
4. Sickle cell: Crescentic shape as in sickle cell anemia.
5. Poikilocytosis: Unusual shapes due to deformed cell
membrane. The shape will be of flask, hammer or any
other unusual shape.
12. Variation in structure of RBCs
1. Punctate basophilsm; RBCs are striated in
appearance due to presence of dots
2. Ring in RBCs; in certain types of anemia,
3. Howell-Jolly bodies;
• Presence of nuclear fragments in cytoplasm of
RBCs
13. Properties of RBCs
1. Are capable of synthesizing bicarbonate
which acts as a buffer. (carbonic
anhydrase)
2. RBCs are capable of piling up one on top
of the other like a stack of coins
(rouleaux formation).This enables them
to sediment (ESR)
3. Suspension stability (flowing freely in
blood)
4. Specific gravity of RBC is 1.092 to
1.101.
5. Average Lifespan is about 120 days
14. Origin of cells…
• The process of origin, development and
maturation of all blood cells;- hemopoeisis
or hematopoiesis.
15. Formation of RBCs
• The process of origin, development and
maturation of red cells is erythropoiesis.
• The process begins in the embryonic yolk sac
and is continued in the liver, spleen and lymph
nodes in the maturing fetus.
By the end of pregnancy and after birth,
however, the process is restricted to red bone
marrow
17. Summary of events in erythropoiesis
Stage of erythropoiesis Important event
Proerythroblast Synthesis of Hb starts
Early normoblast Nucleoli disappear
Intermediate normoblast Hemoglobin starts appearing
Late normoblast Nucleus disappears
Reticulocyte Reticulum is formed.
Cell enters capillary from site
of production
Matured RBC Reticulum disappears
Cell attains biconcavity
18. Control of erythropoiesis
• Erythropoiesis is controlled by the kidney,
which releases a hormone known as
erythropoietin if the delivery of O₂ to renal cells
falls below normal.
• It occurs if circulating [Hb] is reduced, i.e.,
during anemia.
• The bone marrow responds by increasing red
cell production, thus increasing the Hb content
back to normal.
19. • Since this control loop is sensitive to tissue O₂ levels
rather than the actual Hb concn, other conditions which
reduce the O₂ content of blood will also stimulate
erythropoiesis, even if the Hb concn is normal.
• This is seen at high altitudes, where the partial pressures
of O₂ in the lungs and blood are reduced.
• Over a period of weeks at high altitudes, erythropoietin
stimulates an increase in the Hb concn, with a rise in
PCV and red cell count (compensatory polycythemia).
• It is for this reason that athletes wishing to increase the
O₂-carrying capacity of their blood often train at high
altitudes
22. Requirements for Erythropoiesis
In addition to erythropoietin;
1. Vit B12 and folic acid are required for DNA
formation at early stages
Deficiency of either leads to maturation failure
2. Iron is for Hb formation; deficiency leads to
hypochromic anemia
3. Intrinsic factor is required for absorption of Vit
B12 from GIT
23. Hemoglobin (Hb)
• Hb is the iron containing coloring matter of
RBC
-[Hb] is 15g/dL (14-18) in adult males
-[Hb] is 14g/dL (12-16) in adult females
-[Hb] is 14-20g/dL in infants
• In fetus it is HbF and in adults its HbA
• HbF has a higher affinity for oxygen compared
to HbA.
24. Erythrocyte sedimentation rate (ESR)
• ESR is also called sedimentation rate, sed rate
or Biernacki reaction
• ESR is the rate at which the RBCs settle down.
• Normally, RBCs remain suspended uniformly
in circulation
• If blood is mixed with an anticoagulant and
allowed to stand on a vertical tube, the red
cells settle down due to gravity with a
supernatant layer of clear plasma.
• Can be determined using a Westergren or
Wintrobe tube.
25. Factors affecting ESR…..
Factors increaseing ESR
1. Specific Gravity of RBC
2. Rouleaux Formation
Globulin and fibrinogen
accelerate the rouleaux
formation.
3. Increase in size of RBC.
When the size of RBC
increases (macrocyte), ESR
also increases.
4. Anemia except sickle cell
anemia
Factors decreasing ESR
1. Increased viscosity of Blood
Viscosity offers more
resistance for settling of RBCs.
2. RBC count
When RBC count increases,
the viscosity of blood is
increased and ESR decreases.
And when the RBC count
decreases, ESR increases
3. Sickle cell anemia
26. Packed cell volume (PCV)
• Also called hematocrit value or
erythrocyte volume fraction
(EVF).
• It is the proportion of blood
occupied by cells.
• Its expressed as a percentage.
• It is the volume of RBCs packed
at the bottom of a hematocrit
tube when the blood is
centrifuged.
• Normal PCV:males= 40%-45% ;
females= 38% - 42%
27. Variations in PCV…
• Low PCV values can be indicative of anemia while
high PCV values can be indicative of polycythemia.
• The hematocrit is decreased in a variety of common
conditions including chronic and recent acute blood
loss, some cancers, kidney and liver diseases,
malnutrition, vitamin B 12 and folic acid deficiencies,
iron deficiency, pregnancy, systemic lupus
erythematosus, rheumatoid arthritis and peptic ulcer
disease.
• An elevated hematocrit is most often associated with
severe burns, diarrhea, and dehydration
28. RBC indices…
• Are calculations derived from RBC count, Hb content
of blood and PCV.
• Help in diagnosis of the type of anemia
1. Mean corpuscular volume; Is the average volume of a
single RBC; MCV=
𝑃𝐶𝑉 𝑥10
𝑅𝐵𝐶(10⁶/µL)
fL
1. Mean corpuscular hemoglobin: Is the quantity of Hb
present in one RBC; MCH=
𝐻𝑏𝑥10
𝑅𝐵𝐶(10⁶/µL)
pg
2. Mean corpuscular Hemoglobin concn; Is the
concentration of Hb in one RBC
MCHC=
𝐻𝑏𝑥100
𝑃𝐶𝑉
g/dL
Side work
If pcv is 39%,
Hb is 14g/dL
and total RBC
is 4.5x
10⁶/mm3
MCV=??/
MCH=??
MCHC=??
29. Review questions…
1. Control loop for erythropoiesis directly responds to..
2. Normal PCV is about……
3. Normal RBC count is about…………….
4. The two proteins that promote rouleaux formation…
5. ESR is high in all anemia except in……..
6. Most red cell meet their demise in …………
7. ESR increases with …………….. In viscosity of
blood
8. The main hormone for erythropoiesis is …… and
mainly produced by ………..
9. Deficiency of these can cause maturation failure of the
RBCs………….
30. Anemia…
Anemia is the blood disorder, characterized by the
reduction in:
1. Red blood cell (RBC) count
2. Hemoglobin content
3. Packed cell volume (PVC).
Generally, reduction in RBC count, Hb content and PCV
occurs because of:
1. Decreased production of RBC
2. Increased destruction of RBC
3. Excess loss of blood from the body.
31. Classification of anemia
• Can be classified based on its cause or
morphology of RBCs
• Hence;
1. Etiological classification (cause)
2. Morphological classification (based on indices)
33. 1. Iron deficiency anemia
• Erythrocytes contain less Hb than normal (they are
hypochromic) and are, as a result, smaller than normal
(microcytic).
• Iron-deficiency anemia can occur whenever iron
demand exceeds supply.
• That may be because of reduced iron intake or
increased iron loss, e.g., because of chronic bleeding.
• Men normally lose approximately 1 mg of iron daily,
chiefly through the shedding of intestinal epithelium.
• In menstruating women, this can rise to 2 mg or more.
33
34. 2. Hemorrhagic anemia
• Results from blood loss (of course includes
RBC loss).
• May be from any form of injury that
damages the blood vessels.
• Iron deficiency anemia can be secondary to
hemorrhagic anemia.
34
35. 3. Hemolytic anemia
Here; RBCs rupture prematurely;
This can be due to:
• Hb abnormalities
• Mismatched blood transfusion
• Parasitic infection like malaria
• Sickle cell anemia
• Hereditary spherocytosis
• an auto immune condition.
35
36. Hemolytic anemia…
Sickle cell anemia
• A mutation in the gene for the
beta chain of Hb results in an
abnormal hemoglobin called
HbS.
• Under low-oxygen conditions,
the beta chains link together and
become stiff rods. This gives the
RBC a sickle shape.
• Sickled RBCs can then block and
clog small blood vessels.
36
37. 4. Aplastic anemia
• The cells are normochromic and normocytic.
• Results from destruction of red bone marrow
by toxic chemicals, drugs, radiation,
invasion of the marrow by cancer cells.
• Impacts all blood cells, leading to clotting
difficulties and immune problems.
37
38. 5. Pernicious anemia
• Can be caused by inadequate absorption of
vitamin B₁₂.
• Usually absence of intrinsic factor is the main
cause
• Red cells are megaloblastic/macrocytic but not
pale.
41. How does anemia affect the circulatory system?
• Severe anemia – reduces viscosity of blood by about
1.5x that of water.
• Thus more blood flows to the tissues and also return to
the heart than required.
Hence;
• Increased cardiac output
• Increased workload on the heart
Incase of exercise by the anemic victim;
• Extreme tissue hypoxia results and; acute cardiac failure
occurs afterwards
42. Polycythemia…
• If the RBC count is more than normal, such
state is called polycythemia
• Can be secondary polycythemia or P. vera
1. Secondary polycythemia
-results from any condition that causes tissue
hypoxia or little O2 in the breathed air.
-commonest example is physiologic
polycythemia as in the natives of high altitude.
43. Polycythemia vera
• It is pathological
• Abnormal persistent increase in RBC count;
>7million/µl
• It is due to malignancy of the bone marrow
• Hematocrit is 60-70% instead of 40-45%
• Viscosity increases upto 10x that of water instead of
3x
• WBC count increases along
• Its is referred to as erythremia /primary polycythemia
44. How does polycythemia
affect the circulatory system?
• Because of the greatly increased viscosity
of the blood in polycythemia, blood flow
through the peripheral blood vessels is often
very sluggish
• Hence larger than normal quantity of Hb is
deoxygenated hence skin assumes a bluish
tint (cyanosis)
45. Why should total RBCs in
circulatory system be regulated
within normal limits?
It is regulated so that?
1. An adequate number of red cells must be
available to provide sufficient transport of
oxygen from the lungs to the tissues
2. Cells do not become so numerous that they
impede blood flow
3. Cells do not reduce greatly to cause rapid
48. References…
1) Guyton and Hall (2015): Textbook of Medical
Physiology. 13th Edition.
2) Sembulingam (2012): Essentials of Medical
Physiology. 6th Edition.
3) Sherwood, L. (2015). Human physiology: from
cells to systems, Cengage learning.
4) William F. Ganong (2003): Review of Medical
Physiology. 23rd Edition.