HEMATOLOGY RED BLOOD CELLS “BEST MODULE EVER”

AY 2019 -2020 Dr. Galang & Dr. Baccay

Module 3 09/16/19

BLOOD COMPONENTS
LEARNING OBJECTIVES • Blood is centrifuged to separate the Formed Elements from
• Identify the morphology and physiologic functions of red blood the Plasma.
cells • PLASMA (55%) + FORMED ELEMENTS (45%) = WHOLE
• Discuss the molecular structure and metabolism of hemoglobin BLOOD
• Correlate diseases relative to red blood cells

OUTLINE
I. Blood VI. Iron
a. Functions a. Iron absorption in GI
b. Characteristics tract
II. Blood Components b. Iron transfer and
a. Hematocrit recycling
b. Serum vs. Plasma VII. Erythropoiesis
c. Formed elements a. Stages
III. Hematopoeisis b. Maturation
IV. Red Blood Cells c. Factors affecting
V. Hemoglobin (Hb) erythropoiesis
a. Fetal Hemoglobin d. Regulation of
b. Hemoglobin conversion erythropoiesis
and recycling VIII. RBC indices Figure 1. Blood composition

BLOOD A. HEMATOCRIT
1. 45% of the whole blood
“Blood is a specialized connective tissue.” 2. Clinically important
A. FUNCTIONS 3. It is the proportion of the cellular components in ratio to the
1. Transports dissolved gases, nutrients, hormones and whole column of the blood sample
metabolic wastes. 4. Amount of packed cell volume (PCV)
• oxygen from lungs to tissues and vice versa 5. It is the volume percentage of the RBCs in blood
6. Normal Value: Male = 40-54% Female = 37-47%
• metabolic wastes of cells (ex. urea and creatinine) to
the kidneys for excretion
"Males have higher hematocrit values than females because
• materials (ex. lipids) from the gastrointestinal tract to males have testosterone that has a role in formation of RBCs
tissues and liver (for storage) and females have monthly menstruation (discharge/loss of
blood)."
2. Restricts fluid loss
• Platelets and clotting proteins minimize blood when a **Also, production of blood is regulated by metabolism, males
blood vessel is damaged. tend to have a higher metabolic demand and greater muscle
mass
3. Regulates B. SERUM VS. PLASMA
• Body Temperature 1. Serum
- When the body gets cold, there is a need to conserve • Plasma without clotting factors
body heat; hence, blood vessels in the skin constrict. • Does not have fibrinogen
There would be less blood flow and less heat loss by
2. Plasma (non-cellular components)
conduction and convection.
• pH and electrolyte composition of the interstitial • Produced mainly from liver, have fibrinogen
fluids
 • Fluid component of blood
- Hemoglobin is a good buffer, which prevents rapid • Contains mostly water (92%)
change in pH. • Has other solutes (1%)
B. CHARACTERISTICS OF BLOOD • Also contains Plasma Proteins
1. Blood volume (liters) = 7% of the body weight (kg)
• Adult male: 5 to 6L Albumin (60%) • Transport substances such as
• Adult female: 4 to 5L fatty acids, thyroid hormones,
2. Temperature is 38 °C and steroid hormones
3. Color range • Major protein in blood and
• Oxygen-rich blood is scarlet red produced from liver
• Oxygen-poor blood is dull red Globulin (45%) • Antibodies, immune function
4. High viscosity (thickness, 5x more viscous than H2O) aka immunoglobulins • Can be divided into alpha,
5. Slightly alkaline pH (7.35 - 7.45) beta, and gamma globulins
• Acidic – decrease pH, more H ions in blood Fibrinogen (4%) • Functions in blood coagulation
• Alkaline – increase pH, less H ions in blood
**lungs and kidneys regulates pH

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 Clinical Correlation:
• Patients with liver diseases manifest with “Edema”
because the liver is where proteins are synthesized
• With a liver damage, plasma protein decreased. In such
situation, the plasma will be pushed toward the
interstitial space. 


3. How serum and plasma are obtained

• Blood is centrifuged to remove cellular components, Anti-
Figure 2. RBC structure
coagulated blood yields PLASMA containing fibrinogen
and clotting factors. Coagulated blood (clotted blood)
yields SERUM without fibrinogen and clotting factors. 1. Anemia – decrease number of RBCs
2. Polycythemia – increase number of RBCs
C. FORMED ELEMENTS 3. Sickle Cell Anemia – decrease flexibility of cell
1. Red Blood Cells (RBCs) or Erythrocytes: Transport membrane of RBC
oxygen and help transport carbon dioxide 4. Thalassemia - an inherited blood disorder characterized
2. White Blood Cells (WBCs) or Leukocytes: Part of the by less hemoglobin and fewer RBCs in body than normal
immune system 5. Porphyrias – group of disorders caused by
3. Platelets or Thrombocytes: Cell fragments involved in abnormalities in the pathway of biosynthesis of heme 

clotting 6. Microcytic – RBCs are smaller than normal
**Fragments of cytoplasm of megakaryocytes which is found in 7. Macrocytic – RBCs are larger than normal
bone marrow
HEMOGLOBIN
HEMATOPOEISIS
1. Globular protein; complex quaternary structure
• Process of producing the formed elements
2. Iron-containing protein
• Prenatally, hematopoiesis begins in the yolk sack 3. The red pigment that gives whole blood its color
then in the liver, and lastly in the bone marrow.
4. Major type of Hb: HbA1 – consists of 2 a and 2 b chains
• Hematopoiesis in adults occurs in the bone marrow
5. Normal Value: Male = 14-18g/dL Female = 12-16g/dL
• All cells circulating blood begin their lives inside the
bone marrow from a single Pluripotent or Multipotent FUNCTIONS:
Hematopoietic Stem Cells 6. Binds O2 in the lungs and transport it to cells of the tissues
• HSC give rise to two progenitor cells (myeloid and +
7. Also, transports CO2 and H from the tissue to lungs
lymphoid) 8. Carry and release NO (nitric oxide) in the blood vessels
o Lymphoid cells T and B Lymphocytes of the tissues *NO – a potent vasodilator and inhibitor of
o Myeloid cells Thrombocytes, RBCs, platelet aggregation
Granulocytes, and Monocytes

Organ Responsible for Red

Stage of Life
Cell Production
rd
3 week of gestation Yolk sack
th
6 week Liver
rd
3 trimester and after birth Bone marrow takes over
Vertebrae, ribs, sternum,
20 years and above
ilia, bone marrow of the skull
Table 1. Red blood cell production

RED BLOOD CELLS (ERYTHROCYTES)

MAJOR FUNCTION: Carries hemoglobin in the circulation and
Figure 3. Heme and Hemoglobin structure
HEMOGLOBIN inside the RBCs CARRIES THE OXYGEN in return
9. Contain a heme prosthetic group, consisting of four
1. Lacks nuclei (no DNA), mitochondria (no Electron
globin subunits of pyrrole linked by a-methylene
Transport Chain), and ribosome (no new protein
bridges or salt bridges
synthesis)
10. Recall: prosthetic group – the nonpolypeptide chain
Ø Means no repair and anaerobic metabolism
that forms a functional part in the protein
2. Shape: biconcave or discoid
Protein with prosthetic group = holoprotein;
3. Diameter: 6-8um (central pallor: 1/3 of the whole
without = apoprotein
diameter of cell)
11. Heme type of hemoglobin is protoporphyrin IX
4. Thickness: 2um (thin in middle and thicker at edge)
12. Each polypeptide has a heme ring with a pocket
5. Contains a large quantity of carbonic anhydrase
where the iron molecule can interact with oxygen
6. Diapedesis: during reticulocyte stage, the cells pass
13. Four Hb chains: Alpha, Beta, Gamma, and Delta
from the bone marrow into the blood capillaries by
o Most common in adult: HbA
squeezing through the pores of the capillary membrane
o 2a and 2b chains
7. Contains Hemoglobin (Hb), that gives blood its color
8. Flexible – enables RBC to undergo changes in shape o Each with 1 molecule of heme, and each
9. Life span: 120 days heme contains 1 iron ion
10. Rouleaux formation – stacking up of RBC aggregates
in small vessels FETAL HEMOGLOBIN
• High affinity for oxygen
• Strong form of hemoglobin found in embryos
• Takes oxygen from mother’s hemoglobin

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 oCeruplasmin – ferroxidase that
HEMOGLOBIN CONVERSION AND RECYCLING facilitates transfer of iron from ferritin to
1. Macrophages of liver, spleen, and bone marrow transferrin
o Monitor RBCs • Transferred into plasma
o Engulf RBCs before membranes rupture (hemolyze) o Apotransferrin – transport protein
2. If hemoglobin released by hemolysis is phagocytized: o Ferroportin – specific iron channels
o Hemoglobin breaks down o Hephaestin – facilitates iron transport;
o a and b chains – filtered in the kidneys and eliminated has copper. (Copper deficiency will
in urine decrease iron absorption)
Hemoglobinuria – urine may turn red or brown if there’s o Transferrin – apotransferrin with iron
an abnormally large amount of RBC breakdown due to o Hepcidin – main iron regulating protein,
excess hemolysis decreases iron absorption by decreasing
Hematuria – presence of intact RBCs in urine (due to ferroportin
kidney damage or damage to vessels along the urinary
tract) B. IRON TRANSFER/ RECYCLING
3. Globular proteins – disassembled into their component 1. Iron exists as transferrin (protein transporter) in
amino acids circulation
4. Heme unit – each unit will be stripped of its iron and 2. Most of the iron used for RBC hemoglobin production
converted to biliverdin (green color) which will be comes from the hemoglobin breakdown of hemolyzed
converted to bilirubin (orange-yellow pigment) exerted cells (recycling)
by liver (bile) and released into the bloodstream 3. Once iron is removed from the heme leaving biliverdin:
5. Bilirubin – binds to albumin o Utilized as part of enzymes
• Transported to liver for excretion in bile o Storage form of ions: Ferritin & Hemosiderin
• Jaundice – yellowing of skin and eyes due to high o Exported via Ferroportin
circulating levels of bilirubin which happens when the
ERYTHROPOIESIS
bile ducts are blocked or the liver cannot absorb or
• Production of Red Blood Cells (RBC)
excrete bilirubin • Produced only in myeloid tissue (red bone marrow) in
• Large intestine – bacteria convert bilirubin to: adults
o Urobilinogens – some are absorbed into the **hematopoietic cells: stem cells mature to become RBCs
bloodstream and excreted into urine
o Stercobilinogens – on exposure to oxygen, some A. STAGES OF ERYTHROPOIESIS
of the urobilinogens and stercobilinogens are 1. Pluropotential Hematopoietic Stem Cell (HSC):
source from which all circulating blood cells are derived
converted to urobilins (makes urine yellow) and
2. Committed Stem Cells: have become committed to a
stercobilins. Both make feces yellow-brown or particular line of cells
brown depending on the proportion of urobilins 3. Colony forming unit – erythrocyte (CFU-E): a
and stercobilins. committed stem cell that produces erythrocytes
4. Growth inducers: multiple proteins which control the
in lungs, oxygen binds with heme iron growth and reproduction of the different types of
portion to form oxyhemoglobin committed stem cells (eg. Interleukin-3)
5. Differentiation inducers: promote differentiation of
when blood reaches body tissue cells; convert committed stem cells to adult form
capillaries, hemoglobin releases
oxygen first into interstitial fluid and
then to cell for its cellular metabolism
Pluropotential Hematopoietic Stem Cell (HSC) Committed
stem cells Colony forming unit – erythrocyte (CFU-E)
carbon dioxide will bind to globin to
form carbaminohemoglobin, higher Proerythroblast (ProE) Basophilic erythroblast (BasoE)
affinity than O2 Polychromatophilic erythroblast (PolyE) Orthochromatic
erythroblast (OrthoE) Reticulocyte Erythrocyte (RBC)

as blood flow to the lungs, carbon

dioxide is released by hemoglobin
and then exhaled B. ERYTHROCYTE MATURATION
Figure 4. Binding of oxygen to Hb

IRON
1. Mostly found in Hemoglobin
2. Ferritin – stored iron
3. Transferrin – transport form of iron
4. Myoglobin and Plasma – has small amount of irons


A. IRON ABSORPTION IN GI TRACT
1. Dietary iron from either inorganic or animal sources
2. Dietary iron enters intestinal cell wherein it will be:
• Used (incorporated into enzymes)
• Stored as Ferritin
o Becomes hemosiderin when oxidized

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1. Proerythroblast or Rubriblast: D. REGULATION OF ERYTHROPOIESIS
• Basophilic, with nucleoli 1. Stimulated by hypoxia
• Upon stimulation, large number • Reduced number of RBCs
of these cells are formed from • Reduced availability of O2
the CFU-E stem cells 2. Inhibited by rise in circulating RBC levels
• Divides multiple times, 3. Controlled by circulating hormone called
eventually forming many Erythropoietin (EPO) also known as, “erythropoiesis-
mature RBC stimulating hormone”
• Synthesized by both kidneys
2. Basophilic erythroblast or • Produced in juxtaglomerular cells of kidney
Prorubricyte:
• Cytoplasm: blue – due to o Adjacent peritubular fibroblast
abundant RNA • Principal stimulus for RBC production
• No granules, no nuclei • Released in response to tissue hypoxia
• Smaller than the • EPO binds the EPO-receptor (cytokine receptor)
proerythroblast with a smaller resulting to JAK2 & STAT5 activation
nucleus but a more basophilic
cytoplasm **Thyroid hormone and testosterone play much smaller roles in
erythropoiesis
3. Polychromatophilic erythroblast **People living in high altitudes where oxygen is not as abundant
or Rubricyte:
st
• 1 stage of hemoglobin in low lands, more RBC is produced
produced
• Its cytoplasm appears greyer RBC INDICES
due to increased acidophilic
staining caused by the o RBC COUNT
Male: 4.5 – 6.3 million
presence of Hb Concentration of RBCs in
Female: 4.2 – 5.5 million
• Basophilia is from staining of whole blood
ribosomes and acidophilia from o HEMOGLOBIN
Male: 14-18g/dL
hemoglobin Concentration of Hb in
Female:12-16g/dL
4. Orthochromatic erythroblast or whole blood
Metarubricyte: • HEMATOCRIT Male: 40-54%
• Last stage that possess Fraction of blood volume Female: 37-47%
nucleus that consists of intact RBCs Anemia
• More production of hemoglobin (expressed as percentage) Polycythemia
• More darker and solid, showing o MCV 80-96 fL
true colors (Mean Corpuscular Volume) MCV = IDA (Microcytic)
5. Reticulocyte Average volume of a single MCV = FAD & Vit. B12
• Index of RBC production RBC Deficiency (Macrocytic)
• Immediate precursor before • MCH
maturation of RBC (Mean Corpuscular Hb)
• Cell passes from bone marrow Average amount of Hb
into the blood capillaries by within a single RBC
diapedesis • MCHC 27-34 pg/ul
• Contains ribosomes (RNA) (Mean Corpuscular Hb MCV = IDA (Hypochromic)
Concentration) MCV = FAD & Vit. B12
**remnants of RNA
6. Erythrocyte or Red Blood Cell Deficiency (Hyperchromic)
• No nucleus, nucleus extruded o RDW
• RNA is lost (Red Cell Distribution Width)
• Final product of erythropoiesis A measure of the variation in
and is released from bone RBC size
o Measured Values IDA – Iron Deficiency Anemia
marrow into circulation
• Calculated Values FAD – Folic Acid Deficiency

C. FACTORS AFFECTING ERYTHROPOIESIS References:

th
1. Amino acids (1) Hall, J. E., & Guyton, A. C. 13 Ed. (2015).
Blood cells,
2. Iron – essential component of Hb Immunity and Blood coagulation. Guyton and Hall
3. Vitamin B12 (Cobalamin) and B6 (Pyridoxine) textbook of medical physiology.
• Improve utilization of FA (2) PPT by Dr. Galang
4. Folic acid (3) Videos by Dr. Baccay

• Essential for synthesis of DNA

Folic Acid Deficiency

ü Megaloblastic Anemia - Described as macrocytic
and hyperchromic. 

Vitamin B12 Deficiency
ü Pernicious Anemia - A condition characterized by
the absence of parietal glands in the stomach which
are needed for the secretion of intrinsic factor

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