MODULE 14 – HEMATOLOGIC SYSTEM I: RED BLOOD CELLS, ANEMIA, & POLYCYTHEMIA

THE DIFFERENT COMPONENTS OF THE BLOOD o ⅔ of total body of water = ICF

LIQUID COMPONENT
PLASMA AS PART OF THE EXTRACELLULAR
COMPARTMENT OF THE BODY
 Plasma is an aqueous solution of PH 7.4, containing
substances of low or high molecular weight that make up
7% of its volume.
 The dissolved components are mostly plasma proteins, but
they also include nutrients, respiratory gases, nitrogenous
waste products, hormones, and inorganic ions collectively
termed as electrolytes.
 The interstitial fluid is the part of the ECF that is outside the
vascular and lymph systems, bathing the cells.
 The plasma and the cellular elements of the blood,
principally red blood cells, fill the vascular system.

PLASMA VS SERUM

 Plasma leaves the capillaries and small venules to enter the

connective tissue spaces as extracellular fluid, which thus
has a composition of electrolytes and small molecules
similar to that in plasma.
 Concentration of proteins (extracellular fluid) - lower than
that in plasma SOLUTES IN THE BLOOD
 The composition of plasma is usually an indicator of the PROTEINS, WITH ALBUMIN AS IN-CHARGE OF
mean composition of the extracellular fluids in tissues ONCOTIC PRESSURE OF BLOOD
 The major plasma proteins include the following:
o Albumin  Plasma is an aqueous solution, pH 7.4, contains
o Globulins (alpha and beta-globulins) substances of low or high molecular weight that make up
o Immunoglobulins (antibodies or y-globulins) 7% of its volume.
o Fibrinogen  The composition of plasma is usually an indicator of the
o Complement Proteins mean composition of the extracellular fluids in tissues.
 Important Reminder!!! o Proteins
o ⅓ of total body of water = ECF o Glucose

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o Lipids technique, salt-soluble serum protein fraction

o Enzymes separated into five major components designated
o Hormones  Albumin
 α1-Globulins (α1-fetoprotein, α1-antitrypsin)
 α2-Globulins (haptoglobin, ceruloplasmin, and α2-
macroglobulin)
 β-Globulins (transferrin, C-reactive protein)
Transport iron and lipids in blood stream
 γ-Globulins [immunoglobulins (Ig) G,A,M,D,E]
Antibodies

 Proteins - The proteins that circulate in blood plasma play

important roles in human physiology
o Macromolecules, synthesized in the liver, secreted by
hepatocytes to circulation
o Composition of Elements: Carbon, Hydrogen, Oxygen,
Nitrogen, and Sulfur (CHONS)
 Plasma contains a complex mixture of proteins. Early
scientists classified these proteins into three groups,
fibrinogen, albumin, and globulins, on the basis of their
relative solubility in the presence of added organic solvents
such as ethanol or salting out agents such as as ammonium
sulfate
 Albumin - facilitate the transit of fatty acids, steroid
hormones, and other ligands between tissues
o Liver- 12g of albumin per day (40% of it circulates in
plasma (3/5 of total plasma protein or 3.4-4.7 g/dL))
o Because of its relatively low molecular mass (about 69
kDa) and high concentration,albumin is thought to
contribute 75 to 80% of the osmotic pressure of  Fibrinogen - The largest plasma protein and it participates
human plasma in blood coagulation (clotting); precursor of fibrin
o 25% of total hepatic protein synthesis (Made in the o Serves as a readily mobilized building block of the fibrin
liver) mesh that provides the foundation ofthe clots used to
o Maintains the appropriate fluid balance in the tissue seal injured vessels
o A major role of albumin is to bind to and transport  Regulatory proteins (Complement Proteins) - Consists
numerous ligand (free fatty acids (FFA), calcium, of enzymes, proenzymes, hormones, and the complement
certain steroidhormones, bilirubin, copper, and system
tryptophan. A variety of drugs, including sulfonamides, o Defensive system important in inflammation and
penicillin G, dicumarol, and aspirin, also bind to destruction of microorganisms
albumin)
o Preparations of human albumin have been widely used
in the treatment of burns and of hemorrhagic shock
o Buffers pH and is a negative acute-phase reactant
protein
o has the largest capacity to bind hormones
 Globulin - The globulins are insoluble in water
o Made by the liver and other cells, include transferrin
(aids the uptake and distribution of iron)and other
transport factors; fibronectin; prothrombin, and other
coagulation factors; lipoproteins and other proteins
entering blood from tissues
o Subsequently, clinical scientists employed
electrophoresis within a cellulose acetate matrix to
analyze the protein composition of plasma. Using this

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GLUCOSE & LIPIDS
 The lipids are a heterogeneous group of compounds,
including fats, oils, steroids, waxes, and related
compounds, that are related more by their physical than by
their chemical properties. They have the common property
of being:
o relatively insoluble in water
o soluble in nonpolar solvents such as ether and
chloroform
 They are important dietary constituents not only because of
the high energy value of fats but also because essential
fatty acids, fat-soluble vitamins, and other lipophilic
micronutrients are contained in the fat of natural foods
 Function: Energy Storage
 Composition: Mostly Carbon & Hydrogen with some
Oxygen
 Characteristics:
o Hydrophobic (Hate water)
o Insoluble in water
o Soluble in nonpolar solvents: Ether and chloroform
o Lipids include fats (most abundant), steroids, and
terpenes.
o Fats are carboxylic esters derived from glycerol and
are also known as glycerides
 Simple lipids - fats and waxes
 Complex - Phospholipids, Glycolipids, lipoproteins
 Derived-formed from hydrolysis of both simple and complex
fatty acids, glycerol other alcohols, fatty aldehydes, ketone
bodies, hydrocarbons, lipid-soluble vitamins and
micronutrients, and hormones.
 4 Major Lipid classes in the plasma as lipoproteins:
o Triacylglycerols (16%)
o Phospholipids (30%)
o Cholesterol (14%)
o Cholesteryl esters (36%)
o A much smaller fraction of unesterified long-chain fatty
acids (or FFAs) (4%)
 The FFA is metabolically the most active of the
plasma lipids
 Fatty acids - Simplest
o Building blocks of lipids
o Saturated (no double bonds) or unsaturated (with
double bonds)
 Cholesterol - Not readily catabolized = not a source of fuel
o Two forms: esterified (60-70%) and free cholesterol
(30-40%)
o An important constiuent of cell membranes and a
precursor of many hormones
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 Triglyceride - three molecules of fatty acids + one molecule
of glycerol
o is made up of fatty acids and glycerol and is partly
synthesized in the liver hepatocyte
o transported through the bloodstream by chylomicrons
and very low-density lipoproteins (VLDLs)
o Function: Provides energy to cells as it loses its fatty
acid and forms ATP, thus acting as an energy store in
the form of fat, and it insulates organs through fat
deposits
 Phospholipids - make up the bilayer of cell membranes
and also form a coating that surrounds cholesterol and
triglyceride and “glues” them to the lipoprotein core
 Sphingolipids - important in cell membrane composition
and in nerve transmission
 Lipid composition of food:
o Triglycerides comprise 98% of fat found in food and are
made up of 95% fatty acid and 5% glycerol
o Fatty acids are long carbon chains joined by single
(saturated) or double bonds (unsaturated) and a
terminal carboxyl group
o The remaining 2% of fat in food is composed of
cholesterol, phospholipids, diglycerides, fat-soluble
vitamins, steroids, and terpenes
 The physiology of lipids involves three phases:
o Digestive phase - begins with chewing and
swallowing
 Triglycerides are digested by lipase, other
enzymes, bile salts, and acid in the gut to form
monoglycerides and diglycerides
 Cholesterol becomes surrounded by bile to form a
micelle package that is absorbed by the small
intestine
o Absorptive phase - occurs in the small intestine as
triglycerides and cholesterol in the micelles are
absorbed and broken down into fatty acids
o Transport phase - occurs as long fatty acids resemble
into chylomicrons (water soluble macromolecules) and
enter the lymphatic system
 Short fatty acids enter the blood bound to albumin,
and these head to all tissues, including adipose
tissue.
 Fat absorbed from the diet and lipids synthesized by the
liver and adipose tissue must be transported between the
various tissues and organs for utilization and storage
 Since lipids are insoluble in water, the problem of how to
transport them in the aqueous blood plasma is solved by
associating nonpolar lipids (triacylglycerol and cholesteryl
esters) with amphipathic lipids (phospholipids and
cholesterol) and proteins to make water-miscible
lipoproteins
 4 Major groups of plasma lipoproteins :the transport vehicle
of proteins:
o Chylomicrons - derived from intestinal absorption of
triacylglycerol and other lipids
 package fatty acid, monoflyceride cholesterol and
apoproteins
 Large molecules that contain mostly triglyceride.
 Originate in the intestinal tract and travel through
the blood and lymph to various tissues.
 They are degraded in the liver
 Chylomicrons arrive in liver , bind to LDL receptors
and enter
o VLDL - derived from the liver for the export of
triacylglycerol
 go into blood, transport TAG for tissues for energy
or storage
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 smaller than chylomicrons
 contain mostly endogenous triglycerides, are
made in the liver
 contain equal amounts of phospholipids and
cholesterol
 degrade to LDLs in the circulation
 Comes across lipase- IDL (intermediate) and
becomes IDL- converted to become LDL
o Lowdensity lipoproteins (LDL) - representing a final
stage in the catabolism of VLDL
 tissues need cholesterol to make hormones,
maintain cell membrane intergrity
 contain mostly cholesterol, with equal amounts of
phospholipid and protein and some triglyceride
 Return to liver- LDL receptor- endocytosed-
recycled or excreted through Bile
o high-density lipoproteins, (HDL) - involved in
cholesterol transport and also in VLDL and
chylomicron metabolism
 Enters circulation- cells in excess cholesterol-
return it to liver- recycled or excreted
 Contain mostly protein, some cholesterol, and a
little triglyceride
 They are made in the liver, and they remove
excess cholesterol from cells
 Carbohydrates - Carbohydrates are widely distributed in
plants and animals; they have important structural and
metabolic roles
 Carbohydrates containing C, H, and O
 Classification:
o Monosaccharides - simple sugars that cannot be
hydrolyzed to a simpler form
GROUP 2 & GROUP 7
 These sugars can contain three, four, five, and six
or more carbon atoms (known as trioses, tetroses,
pentoses, and hexoses, respectively)
 The most common include glucose, fructose, and
galactose
o Disaccharides - formed when two monosaccharide
units are joined by a glycosidic linkage
 The most common disaccharides are maltose,
lactose, and sucrose
o Oligosaccharide - chaining of 2 to 10 sugar units
o Polysaccharides - more than 10 monosaccharides
 Amylase hydrolyzes starch to disaccharides in the
duodenum
 The most common polysaccharides are starch
(glucose molecules) and glycogen
 GLUCOSE: is the most important carbohydrate
o Primary sugar found circulating in the body
 Carbohydrate metabolism:
o Glycolysis: glucose → lactate or pyruvate → energy (↑
glucose)
o Glycogenolysis: breakdown of glycogen to glucose (↑
glucose)
o Glycogenesis: formation of glycogen from sugars for
storage (↓glucose)
o Gluconeogenesis: formation of glucose from non-
carbohydrate sources (↓glucose)
 Normal: <100 mg/dL
 Impaired fasting glucose: 100-125 mg/dL
 Diabetic: >126 mg/dL
 Most dietary carbohydrate is absorbed into the bloodstream
as glucose formed by hydrolysis of dietary starch and
disaccharides, and other sugars are converted to glucose
in the liver
 Glucose is the major metabolic fuel of mammals (except
ruminants) and a universal fuel of the fetus.
 The expected values for normal fasting blood glucose
concentration are between 70 mg/dL (3.9 mmol/L) and 100
mg/dL (5.6 mmol/L)
 The nervous system, including the brain, totally depends on
glucose from the surrounding extracellular fluid (ECF) for
energy
 Nervous tissue cannot concentrate or store carbohydrates;
therefore, it is critical to maintain a steady supply of glucose
to the tissue. For this reason, the concentraƟon of glucose
in the ECF must be maintained in a narrow range
 When the concentration falls below a certain level, the
nervous tissue loses the primary energy source and is
incapable of maintaining normal function
 It is the precursor for synthesis of all the other
carbohydrates in the body, including
 glycogen for storage, ribose and deoxyribose in nucleic
acids, galactose for synthesis of lactose in milk, in
glycolipids, and in combination with protein in glycoprotein
and proteoglycan
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 Factors that affect glucose levels include: HORMONES

o Insulin - a pancreatic hormone  Body’s chemical messengers that travels in the
o That decreases glucose levels by increasing cellular bloodstream to tissues or organs
uptake of glucose and promoting glycogenesis and  Can affect many different processes:
lipogenesis (formation of fat from carbohydrates) o Growth and development
o Glucagon - a pancreatic hormone that increases o Metabolism
glucose levels by stimulating glycogenolysis and o Sexual function
gluconeogenesis o Reproduction
o Epinephrine - an adrenal hormone that elevates o Mood
glucose levels
 Produced by endocrine glands
o Growth hormone and adrenocorticotropic
 Major endocrine glands:
hormone (ACTH) - pituitary hormones that increase
o Hypothalamus - Central controller of the endocrine
glucose levels
system and egulates pituitary glands’ secretion of
o Glucocorticoids - (e.g., corƟsol)- adrenal hormones
hormones
that increase gluconeogenesis and eventually elevate
blood glucose
o Thyroid hormones - stimulate glycogenolysis and
increase blood glucose levels
 Glucose disorders depend on serum glucose levels
o Hyperglycemia occurs when the fasting blood sugar
level rises higher than 110 mg/dL due to a pathologic
disorder, such as diabetes mellitus or liver failure.
o Hypoglycemia occurs when the fasting blood glucose
level is <70 mg/dL. This typically occurs as a result of
hormone deficiency, drug reaction, insulin excess (as
in insulinoma), or a genetic disorder.
o Glycosuria (sugar in the urine) occurs when the renal
threshold for glucose is exceeded (160–180 mg/dL)
during hyperglycemia.
o Diabetes mellitus is a genetic disorder of glucose
metabolism that results in insulin deficiency and lack of
carbohydrate tolerance. There are two classifications:
 Type 1, formerly insulin-dependent diabetes
mellitus.  Pituitary gland - A pea-sized body attached to the base of
 Type 2, formerly non-insulin-dependent diabetes the brain
mellitus.

ENZYMES
 Enzymes are proteins that help speed up chemical
reactions in our bodies.
 Classifications of Enzymes:
o Oxidoreductases - Catalyze an oxidation–reduction
reaction between two substrates
 Examples: LDH, MDH, ICD, G6PD
 Note: Ends with dehydrogenase or oxydase
o Transferases - Catalyze the transfer of a group other
than hydrogen from one substrate to another
 Examples: CK, AST, ALT, OCT
 Note: Ends with kinase or transferase
o Hydrolases - Catalyze hydrolysis of various bonds
 Esterases: ACP, ALP
 Peptidase: Trypsin, Pepsin, LAP
 Galactosidase: AMS, Galactosidase
o Lyases - Catalyze removal of groups from substrates  Pineal - secretes Melatonin
without hydrolysis; the product contains double bonds o A hormone that rises at night, when sunlight is absent
 Example: Glutamate decarboxylase, Pyruvate and falls during the day
decarboxylase o High melatonin levels triggers sleepiness, making it a
o Aldose - Ends with decarboxylase key factor of SLEEP-WAKE CYCLE
o Isomerases - Catalyze the intramolecular  Thymus - secretes Thymosin and Thymopoietin
arrangement of substrate compound o 2 hormones having a role in the development of the
 Example: Glucose phosphate isomerase immune system - T3 (Triiodothyronine) & T4
o Ligases - Catalyze the joining if two substrate (Thyroxine):
molecules, coupled with breaking of the pyrophosphate  Acts to increase the metabolic rate
bond in ATP  Stimulate appetite, digestion, breakdown of
 Example: Glutathione Synthetase Synthase nutrients and absorption
 Increase oxygen consumption, raise the breathing
rate, heart rate and contraction strength

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o Parathyroid - secretes Parathyroid Hormone

 The main hormone the body uses to maintain
normal levels of calcium in the blood.
 Exerts its influence on the bones, kidneys, and
intestines to achieve calcium homeostasis
o Adrenal glands

 Other hormones:
o Erythropoietin (EPO) - a glycoprotein hormone
produced by the peritubular cells of the kidneys ELECTROLYTES WITH SODIUM AS IN CHARGE OF
 Stimulates red bone marrow to produce more red OSMOTIC PRESSURE OF BLOOD
blood cells by increasing the number of  Minerals in blood and other body fluids that carry an electric
proerythroblasts formed and by decreasing the charge
time required for red blood cells to mature.
 PO2 directly regulates EPO production:
 The lower the pO2, the greater the production of
EPO

 Sodium - Major Extracellular Cation

o Represents 90% of all extracellular cations and largely
determines plasma osmolality
o It is the principal osmotic particle outside the cell
o The presence of sodium creates an osmotic pressure,
which attracts water molecules.
o The more solutes there are, the higher the osmotic
pressure

 The fluid state of blood → a protective mechanism,

coagulation (clotting), to stop its flow in case of damage to
the vascular tree.
 Coagulation → is mediated by platelets and blood-borne
factors that transform blood from a liquid to a gel state

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COAGULATION FACTORS AND OTHER GROWTH
FACTORS
 Coagulation factors are proteins in the blood that play a
crucial role in the blood clotting process, also known as
coagulation
 One of the mechanisms for hemostasis is formation of the
blood clot.
 Clotting takes place in three essential steps:
o In response to rupture of the vessel or damage to the
blood itself, a complex cascade of chemical reactions
occurs in the blood involving more than 12 blood
coagulation factors. The net result is the formation of a
complex of activated substances collectively called
prothrombin activator.
o The prothrombin activator catalyzes the conversion of
prothrombin into thrombin.
o The thrombin acts as an enzyme to convert fibrinogen
into fibrin fibers that enmesh platelets, blood cells, and
plasma to form the clot.
o It forms when the body breaks down carbohydrates to
use for energy when oxygen levels are low.
o A test can be done to measure the amount of lactic acid
in the blood.
o Normal results range from 4.5 to 19.8mg/dL
 Creatinine - Creatinine usually enters your bloodstream
and is filtered from the bloodstream at a generally constant
rate
o An increased level of creatinine may be a sign of poor
kidney function.
o The typical range for serum creatinine is:
o For adult men, 0.74 to 1.35 mg/dL
o For adult women, 0.59 to 1.04 mg/dL
 Urea - Urea nitrogen is a waste product that your kidneys
remove from your blood.
o A blood urea nitrogen (BUN) test can provide important
information about your kidney function.
 Bilirubin - A yellowish pigment that is made during the
breakdown of red blood cells.
o Passes through the liver and is eventually excreted out
of the body.
o Higher than usual levels of bilirubin may indicate
different types of liver or bile duct problems.
o Sometimes, higher bilirubin levels may be caused by
an increased rate of destruction of red blood cells
 Ammonia - Also known as NH3
o A waste product made by your body during the
digestion of protein.
o Normally, ammonia is processed in the liver, but if your
body cannot process or eliminate ammonia, it builds up
in the bloodstream.
o High ammonia levels in the blood can lead to serious
o Health problems, including brain damage, coma, and
even death.
GASES
 Oxygen
o Needed for aerobic cellular respiration
o >2% dissolved in plasma
o 98% bound to hemoglobin within erythrocytes
 Carbon dioxide
o A waste product produced by cells during this process
o ~7% dissolved in plasma
o ~27% bound to hemoglobin within
o erythrocytes
o ~66% converted to HCO3-

HYPERVOLEMIA VS HYPOVOLEMIA
 Hypovolemia - Diminished blood volume - Secondary to
sodium and water loss
 Manifestation:
o increase HR,
o low BP (hypotension (90/60]
o pale, cyanotic, cold, dry tongue lips, eyes sunken
o temp low (hypothermic)
o weight loss
o urine output decrease
 Hypervolemia - Aka “Fluid Overload”/”Volume Overload
 Manifestation:
o increase BP
WASTE PRODUCT AND METABOLITES o increase heart rate
o jugular venous pressure inc
 Waste products serve no function in the blood plasma; o edema, jugular pathologic flux, fluid in stomach
 Merely being transported to the liver and kidneys where o gain weight
they can be removed from the blood
 Lactic Acid - It is mainly produced in muscle cells and red
blood cells.

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o SHORT LIFESPAN: Erythrocytes have a lifespan of

about 100-120 days.
 Major function is to:
o Transport hemoglobin
o contain a LARGE quantity of carbonic anhydrase
o The hemoglobin in the cells is an excellent acid-base
buffer (as is true of most proteins), so the RBCs are
responsible for most of the acid-base buffering power
of whole blood.

RETICULOCYTES, MACROCYTES, & MICROCYTES

 Reticulocytes - immature erythrocytes (red blood cells)
that are still developing.
o They are released from the bone marrow into the
bloodstream before they are fully mature.
CELLULAR COMPONENTS o Reticulocytes are larger than mature erythrocytes and
RED BLOOD CELLS (RBC/ERYTHROCYTES) contain ribosomes, which are cellular structures that
 Responsible for carrying oxygen and carbon dioxide. produce proteins.
o Reticulocytes are typically removed from the
 SIZE: 7 to 8 micrometer
bloodstream after 1-3 days, but they may remain in
 Lacks nuclei and completely filled with the O2 - carrying
circulation for longer in certain conditions, such as
protein hemoglobin.
anemia.
 Does not require them to leave the vasculature
 Concentration:
o Males: 4,900,000 - 5,500,000; ave. 5,200,000
o Females: 4,400,000 - 5,000,000; ave. 4,700,000

WHITE BLOOD CELLS (WBC / LEUKOCYTES)

 Immune responses, recognizing and neutralizing invaders
such as bacteria and viruses
 5 MAJOR TYPES and is divided into 2 Groups:
o Granulocytes:
 Neutrophils
 Eosinophils
 Basophils
o Agranulocytes - does not have granules in the
cytoplasm
 Monocytes
 Lymphocytes  Macrocytes - unusually large erythrocytes.
o They are most commonly seen in people with vitamin
PLATELETS (THROMBOCYTES) b12 or folate deficiency, but they can also be seen in
 Platelets are responsible for blood clotting people with other conditions, such as liver disease or
 They’re very small non-nucleated, membrane- bound cell hypothyroidism
fragments only 2-4 μm in diameter
 Originate by separation from the ends of cytoplasmic
processes extending from giant polyploid bone marrow
cells called megakaryocytes
 Promote blood clotting and help repair minor tears or leaks
in the walls of small blood vessels, preventing loss of blood
from the microvasculature
 Normal platelet counts range from 150,000 to 400,000/μL
(mm3 ) of blood

BLOOD CELLS ACCORDING TO THEIR

MORPHOLOGY
ERYTHROCYTES
 Also known as red blood cells (RBCs), are the most
common type of blood cell and the principal means of
delivering oxygen (O2) to the body tissues—via blood flow
through the circulatory system  Microcytes - unusually small erythrocytes. They are most
 Features of erythrocytes: commonly seen in people with iron deficiency anemia, but
o Biconcave discoid shape they can also be seen in people with other conditions, such
o Anucleate as thalassemia or sickle cell disease
o High hemoglobin content o Microcytes are less efficient at transporting oxygen
o Lack of organelles than mature erythrocytes, and they may also be more
likely to break down in the bloodstream.

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 Hypochromia, on the other hand, is an abnormality in

which RBCs have an excessively large area of central
pallor.
o This means that there is less hemoglobin in the cells
than normal.
o Hypochromia is often a sign of iron deficiency anemia.

NORMAL SHAPE OF ERYTHROCYTES

 The normal shape of erythrocytes, also known as red blood
cells, is BICONCAVE DISCOID.
 This means that they are disk-shaped with a central
depression on both sides. The biconcave discoid shape
gives erythrocytes several advantages:
o It allows them to have a large surface area to volume
ratio, which maximizes the amount of oxygen that they
can carry.
o It makes them flexible, which allows them to squeeze
through narrow capillaries.
o It helps to prevent them from clumping together.

SHAPE ADAPTATION OF ERYTHROCYTES TO

CHANGES IN VASCULAR CALIBER LEUKOCYTES
 The following are some of the ways that erythrocytes adapt  Are parts of the immune system participating in both innate
to changes in vascular caliber: and humoral immune responses
o Flexible membrane  They circulate in the blood and mount inflammatory and
o Biconcave discoid shape cellular responses to injury and pathogens
o Cytoskeleton
GRANULOCYTES & POLYMORPHONUCLEARS
NORMAL CENTRAL PALLOR VS. HYPOCHROMIA  Neutrophils
 Central pallor - the normal appearance of RBCs, which o Major Functions: kill and phagocytose bacteria
have a light-colored area in the center. o Diameter: 9-15 um
o This area is caused by the fact that the hemoglobin, the o Nucleus: 3-5 lobes
protein that carries oxygen in the blood, is o Specific Granules: Pink to rose violet/light pink
concentrated at the edges of the cell.  Eosinophils
o Major Functions: kill helminth and other parasites, it
also modulate local inflammation
o Diameter: 12-17 um
o Nucleus: bilobed, sausage-shaped

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o Granules: Reddish Orange, have small central
apparatus and limited enough endoplasmic reticulum
and mitochondria
 Basophils
o Major Function: Modulate local inflammatory also
releases histamine during allergy
o Diameter: 14-16 um
o Nucleus: Bilobed, S-shaped nucleus
AGRANULOCYTES & MONONUCLEARS
 Monocytes - Largest circulating blood cell.
o Major Function: Precursor of Macrophages
o Diameter: 25 um
o Nucleus: large, kidney-shaped
o Nucleoli often present
 gives nucleus a “moth-eaten” appearance
Cytoplasm contains many: Lysosomes Vacuole-
like spaces
 produces “ground-glass appearance”
 Lymphocytes
o Smallest WBC (6-15 um)
o Major Function: Effector and regulatory cells for
adaptive immunity
o Round in blood but can change shape outside the
circulation
o Round densely staining, eccentric nuclei with Spare
cytoplasm contain lysosome-like granules called
Azurophilic granules
GROUP 2 & GROUP 7
THROMBOCYTES
 Normal lifespan = 7-10 days (1⁄3 are sequestered in spleen)
 Disc-shaped (2-4 um)
 Maintained by 10-15 parallel microtubules around its
circumference
 Has 2 tubular systems:
o Dense tubular system
o Surface-opening canalicular system
 Non-nucleated
 Has granule-containing cell fragments
 Granules of thrombocytes:
o Alpha Granules - release clotting factors to promote
blood clot formation
o Dense Granule - release substances involved in
platelet aggregation and vasoconstriction
o Lysosomes - contribute to the breakdown of clot
components formed from megakaryocyte cytoplasm
DEVELOPMENT, DIFFERENTIATION OR
MATURATION, & SITES OF HEMATOPOIESIS
SITES OF BLOOD CELL DEVELOPMENT PER AGE
LEVEL
EMBRYO & FETAL STAGE
 In the early embryo these blood cells arise in the yolk sac
mesoderm. In the second trimester, hemopoiesis (also
called hematopoiesis) occurs primarily in the developing
liver, with the spleen playing a minor role.
 Skeletal elements begin to ossify and bone marrow
develops in their medullary cavities, so in the third-trimester
10
 TRANS: Module 14

marrow of specific bones becomes the major hematopoietic o Fibroblast-like interstitial cells surrounding the tubules
organ. in the renal cortex and outer medulla
 Primitive hematopoiesis (1st month of prenatal life) o Renal epithelial cells
 Begins around 19th day of embryonic development after
fertilization
 Starts outside embryo in the mesenchyme of yolk sac as
BLOOD ISLANDS
 Contain predominantly primitive erythroblasts Large,
megaloblastic cells formed intravascularly and retain nuclei
 Definitive hematopoiesis:
o Takes place in Aorta-gonad-mesonephros (AGM)
region of embryo from which hematopoietic cells
migrate to:
 Placenta
 Liver
 Spleen
 At 6th week, hematopoiesis begins in LIVER
 Early and Mid Fetal life:
o hepatic phase begins 5th to 7th week of gestation
o Liver becomes major hematopoietic organ
o Liver produce Definitive erythroblasts
 Middle part of fetal life:
o Spleen and Lymph nodes start to have minor role in
hematopoiesis
o Liver Continues to dominate
 Latter half of fetal life:
o Prior to the 5th month of fetal development
o Bone marrow becomes the major site of blood cell
production by the end of 24 weeks  EPO is produced when tissue oxygenation is decreased
o Liver’s role ceases (Hypoxia)
 How is EPO produced?
INFANT AKA POSTNATAL HEMATOPOIESIS o Renal tissue hypoxia increases Hypoxia-inducible
 Bone marrow - the only site of production of erythrocytes factor-1 (HIF-1) which serves as transcription factor for
(Active site - Red marrow only). Hematopoietic Stem cells EPO
(HSC) and committed progenitor cells are maintained in o HIF-1 binds to Hypoxia response element (HRE) in the
bone marrow EPO gene to induce transcription of mRNA to increase
 B-cell lymphocytes - produced in the BONE MARROW EPO synthesis
and secondary lymphoid organs
 T-cell lymphocytes - Produced in THYMUS and CYTOKINES & INTERLEUKINS
secondary lymphoid organs  These substances often act synergistically with other
growth factors and may act on normal cells as well as
CHILD-ADULT neoplastic cells.
 Throughout childhood and adult life, erythrocytes,  Cytokines
granulocytes, monocytes, and platelets continue to form o Control the proliferation, differentiation, and survival or
from stem cells located in bone marrow. death of various progenitors.
 The origin and maturation of these cells are termed, o They maintain steady-state levels of blood cells in
respectively, erythropoiesis (Gr. erythros, red + poiesis), normal situations and in response to certain stimuli,
granulopoiesis, monocytopoiesis, and thrombocytopoiesis. induce production of a particular cell type
 Sites of blood cell formation:
o Flat bones (Skull, vertebrae, thoracic cage, shoulder
and pelvis) - principal site
o Proximal Parts of Long Bones
o Remaining parts of marrow space is fatty or yellow
marrow which can be replaced by hematopoietic cells
if continuous, intensive stimulation occurs
 Production of granulocytes & macrophages
STIMULANTS & PROMOTERS INFLUENCING
HEMATOPOIESIS
HORMONES - ERYTHROPOIETIN (EPO)
 Production of red blood cells or erythrocytes, is stimulated
by erythropoietin, EPO.
 Produced predominantly by the liver during fetal
development and by the kidneys in adulthood.
 90% of erythropoietin is formed in the kidneys, 10% in liver
 Cells that produce erythropoietin:

GROUP 2 & GROUP 7 11

 TRANS: Module 14

o another for myeloid cells (Gr. myelos, marrow), which

develop in bone marrow.
o Myeloid cells include granulocytes, monocytes,
erythrocytes, and megakaryocytes.

HEMATOLOGIC GROWTH FACTORS

 Erythropoietin (EPO) - production of erythrocytes
 Thrombopoietin (TPO) - production of megakaryocytes
o Production of platelets is stimulated by thrombopoietin,
a hormone secreted by the kidneys and liver.
o Responsible for formation of megakaryocytes - the
gigantic cells that develop as a result of multiple rounds
of DNA replication without cell division.
 Megakaryocytes - give rise to tens of thousands of
platelets, which are essentially broken fragments of its
cytoplasm
 Chemokines - For regulating hematopoietic cell trafficking
and homing
o CXCL12 (SDF-1) - expressed in bone marrow stromal
cells and microvascular endothelial cells
o CXCR4 - expressed by HSCs, it is the receptor for
CXCL12
o CXCL12-CXCR4 signaling - involved in HSC
maintenance & engraftment

STAGES OF DIFFERENTIATION & MATURATION OF

ERYTHROCYTES
 Production of red blood cells or erythrocytes, is stimulated
by erythropoietin, EPO.

PLURIPOTENT STEM CELLS

 Blood cells arise from a single type of pluripotent
hemopoietic stem cell in the bone marrow that can give rise
to all the blood cell types.
 Rare, proliferate slowly and give rise to two major lineages
of progenitor cells with restricted potentials (committed to
produce specific blood cells):
o Lymphoid cells (lymphocytes)
o Myeloid cells (Gr. myelos, marrow)
 Myeloid cells include:
o Granulocytes (Neutrophil, Eosinophil, Basophil)
o Monocytes
o Erythrocytes
 Mature blood cells have a relatively short life span and must o Megakaryocytes
be continuously replaced with new cells from precursors  Lymphoid progenitor cells migrate from the bone marrow to
developing during hemopoiesis. the:
 Stem cells are pluripotent cells capable of asymmetric o Thymus
division and self-renewal. Some of their daughter cells form o Lymph nodes
specific, irreversibly committed progenitor cells, and other o Spleen
daughter cells remain as a small pool of slowly dividing o Other lymphoid structures, where they proliferate and
stem cells. differentiate
 All blood cells arise from a single type of pluripotent
hemopoietic stem cell in the bone marrow that can give rise MULTIPOTENT STEM CELLS: MYELOID AND
to all the blood cell types LYMPHOID
 These pluripotent stem cells are rare, proliferate slowly, and
give rise to two major lineages of progenitor cells with  The blood cells begin their lives in the bone marrow from a
restricted potentials (committed to produce specific blood single type of cell called the multipotential hematopoietic
cells): stem cell, from which all the cells of the circulating blood are
o one for lymphoid cells (lymphocytes) and eventually derived

GROUP 2 & GROUP 7 12


 Colony-Forming Unit–Erythrocyte (CFU-E) - committed
stem cell that produces erythrocytes.
 Multipotent stem cells - aka Neural Stem Cells (NSCs) or
Mesenchymal Stem Cells (MSCs)
DIFFERENTIATION FROM ERYTHROBLAST
ERYTHROCYTES
 Proerythroblast (Rubriblast or Pronormoblast)
o The distinct erythroid progenitor cell
o Large cell with loose, lacy chromatin, nucleoli and
basophilic cytoplasm
o Size: 12-20um
o Nucleoli: 1-2 (usually very faint)
o Nucleus: Round, central or slightly eccentric
o Cytoplasm: small in amount
GROUP 2 & GROUP 7
TRANS: Module 14
o N:C ratio = 8:1
 Basophilic erythroblast (Prorubricyte or Basophilic
Normoblast)
o Slightly smaller with cytoplasmic basophilia
o More condensed nucleus
o First stage of Hemoglobin Synthesis
o Last stage of nucleolus
o Size: 10-15 um
o Nucleoli: 0-1
o Nucleus: smaller
o Cytoplasm: More abundant than normoblast
o N:C ratio = 6:1
 Polychromatophilic erythroblast (Rubricyte or
Polychromatophilic Normoblast
o Cell volume is reduced
o Polysomes decrease
o Some cytoplasmic areas begin to be filled with
hemoglobin, producing regions of BOTH
 Basophilia
 Acidophilia in the cell Size: 10-12um
o Nucleus: eccentric nucleus
o Cytoplasm: Basophilic to diffusely lilac in color; gray
o N:C ratio = 4:1
 Orthochromatophilic erythroblasts (Metarubricyte or
O. Normoblast)
o Cell and nuclear volumes continue to condense
o Basophilia is gradually lost, producing cells with
uniformly acidophilic cytoplasm
o Cell nucleus is ejected and phagocytosis by
macrophages
o last stage of nucleus Size: 8-10 um
o Nucleus: Pyknotic
TO
o Cytoplasm: Salmon-pink
o N:C ratio = 1:2
 Reticulocytes
o Undergoes uniformly acidophilic cytoplasm
o The cell still retains a few polyribosomes which, when
treated with the dye brilliant cresyl blue, form a faintly
stained network
o These cells enter the circulation (where they may
constitute 1% of the red blood cells)
o Quickly lose all polyribosomes, and mature as
erythrocytes.
o last stage of hemoglobin synthesis
o Looks like a mature erythrocyte but is larger and darker
in color
o In normal circumstances, It spend 3 days in marrow
before entering the circulation where it takes about 1
more day to mature
 Mature erythrocyte (RBC)
o Shape - biconcave disk
o Thickness: 1.5 to 2.5 um
o Average life span: 120 days
o Size: 7-8um
o Cytoplasm: Salmon pink (w/ central pallor 1⁄3 dm.)
o No mitochondria (No protein or Hb Synthesis)
 In healthy adults, only 1% of circulating erythrocytes are
reticulocytes
 Normal Ratio of RBC to WBC: 600:1
 Normal Ratio of RBC to Platelets: 15:1
NORMAL RED CELL POPULATION IN DIFFERENT
AGES & BOTH SEXES
 Healthy men average number / cubic millimeter
o 5,200,000 (±300,000)
 Healthy women average number / cubic millimeter
o 4,700,000 (±300,000)
13

 Marrow of essentially all bones produces RBCs - About 5
years old
 20 years old - The marrow of the long bones becomes fatty
and produces no more RBCs
o EXCEPT for the proximal portions of the humeri and
tibiae.
NORMAL PACKED RED CELL VOLUME
DIFFERENT AGES & BOTH SEXES
THE FUNCTION OF ERYTHROCYTES WITH ITS
HEMOGLOBIN CONTENT
 The main role of erythrocytes is transportation and
exchange of gases (oxygen, carbon dioxide) between lungs
and tissues.
 In lung capillaries, hemoglobin binds the inhaled oxygen,
forming oxyhemoglobin. This substance gives erythrocytes,
and hence arterial blood, a bright red color.
 Oxygen rich erythrocytes then travel through the arteries
until they reach tissue capillaries.
 In tissue capillaries, the oxygen is released from
hemoglobin and diffuses into the tissues.
 Simultaneously, the carbon dioxide from the tissues binds
to hemoglobin, forming deoxyhemoglobin. This substance
gives RBCs, and venous blood, a purple blue color.
 Carbon dioxide rich erythrocytes then travel via venous
blood towards the heart, and then to the lungs.
 Within lung capillaries, the carbon dioxide is released from
hemoglobin in exchange for a new dose of oxygen.
RED CELL PORPHYRINS & BIOCHEMICAL
FORMATION OF HEMOGLOBIN
 Porphyrins are cyclic compounds formed by the linkage of
four pyrrole rings through methyne (=HC-) bridges.
Characteristic property of the porphyrins is the formation of
complexes with metal ions bound to the nitrogen atom of
the pyrrole rings.
GROUP 2 & GROUP 7
TRANS: Module 14
 The porphyrin molecule. Rings are labeled I, II, III, and IV.
Substituent positions on the rings are labeled 1, 2, 3, 4, 5,
6, 7, and 8. The methyne bridges (——HC—) are labeled
α, β, γ, and δ. The numbering system used is that of Hans
Fischer.
IN
 Hemoglobin is an oxygen-binding protein found in
erythrocytes that transports oxygen from the lungs to
tissues. Each hemoglobin molecule is a tetramer made of
four polypeptide globin chains.
 Each globin subunit contains a heme moiety formed of an
organic protoporphyrin ring and a central iron ion in the
ferrous state (Fe2+). The iron molecule in each heme
moiety can bind and unbind oxygen, allowing for oxygen
transport in the body.
 The most common type of hemoglobin in adults is HbA,
which comprises two alpha-globin and two beta-globin
subunits. Different globin genes encode each type of globin
subunit.
 The two main components of hemoglobin synthesis are
globin production and heme synthesis. Globin chain
production occurs in the cytosol of erythrocytes and occurs
by genetic transcription and translation. Many studies have
shown that the presence of heme induces globin gene
transcription.
 Genes for the alpha chain are on chromosome 16, and
genes for the beta chain are on chromosome 11.
 Heme synthesis occurs in both the cytosol and the
mitochondria of erythrocytes. It begins with glycine and
succinyl coenzyme A and ends with the production of a
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 TRANS: Module 14

protoporphyrin IX ring. The binding of the protoporphyrin to  Percent saturation of hemoglobin

a Fe2+ ion forms the final heme molecule. o Increase PO2
 Enzymes involved in heme synthesis: o Increase binding of O2 and Hgb
 Oxygenated Blood → Lungs → Systemic Artery
o PO2: 95 mmHg
o Hemoglobin saturation: 97%
 Venous Blood from peripheral tissues
o PO2: 40 mmHg
o Hemoglobin saturation: 75%
 Factors that shift oxygen hemoglobin dissociation
curve:
o pH CHANGES
o CO2 CONCENTRATION
o BLOOD TEMP
o 2,3 BPG

NORMAL CONCENTRATION OF HEMOGLOBIN

 The amount of hemoglobin in whole blood is expressed in
grams per deciliter (g/dl).
 The normal Hb level for males is 14 to 18 g/dl; that for
females is 12 to 16 g/dl.
 When the hemoglobin level is low, the patient has anemia.
 An erythrocytosis is the consequence of too many red cells;
this results in hemoglobin levels above normal.
SHIFT TO SHIFT TO
ROLE OF HEMOGLOBIN IN OXYGENATION & THE
OXYGEN-HEMOGLOBIN DISSOCIATION CURVE THE LEFT THE RIGHT
 97% = oxygen transported from the lungs to the tissues is
carried in a chemical combination with hemoglobin in the pH INCREASE DECREASE
red blood cells.
 3% = remaining is transported in the dissolved state in the PCO2 DECREASE INCREASE
water of the plasma and blood cells.
 Thus, Oxygen is carried to the tissues almost entirely by 2,3 DPG DECREASE INCREASE
Hemoglobin
 Reversible Combination of O2 with Hgb: Temperature DECREASE INCREASE
o When PO2 is HIGH: Pulmonary Capillaries = O2 binds
with hemoglobin
o When PO2 is LOW: Tissue Capillaries = O2 release Hgb affinity INCREASE DECREASE
with hemoglobin for oxygen
 Oxygen dissociation curve:
HEMOGLOBIN AS A MINOR BUFFERING SYSTEM
 Other function:
o Tissue oxygen buffer system
o Hgb in the blood stabilizes PO2 in the tissues
 Hemoglobin helps maintain nearly constant PO2 in the
tissues
o 5 ml of O2 from each 100 ml: tissue requirement of
blood passing through the tissue capillaries in basal
condition.
o PO2 must fall 40 mmHg = 5 ml of O2 to be released
o cannot rise above 40 mmHg; if high, O2 cant be
released from hemoglobin
o 40mm Hg - upper limit on the PO2 in the tissues
 When atmospheric oxygen concentration changes
markedly, the buffer effect of hemoglobin still maintains
almost constant tissue PO2

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 TRANS: Module 14
 Alveoli PO2: 104 mmHg
 In When Alveolar PO2 Decreased to as low as 60mmHg
o Arterial hgb is still 89%
o Only 8% below normal saturation of 97%
o Still remove 5 ml of O2 / 100ml
 To remove this O2
o PO2 venous blood falls to 35 mmHg (only 5 mmHg
below normal)
 When Alveolar PO2 rises as high as 500 mmHg
o Max. O2 sat. of Hgb can never rise above 100%
o 3% above normal level 97%
 This demonstrate beautifully the tissue “oxygen buffer”
function of the blood hgb system
LIFE SPAN OF THE RED BLOOD CELLS AND THE
MECHANISMS OF CLEARANCE OF SENESCENT &
DEGENERATED RED BLOOD CELLS
LIFE SPAN OF RED BLOOD CELLS
 The average lifespan of a red blood cell is 120 days
 Even though mature RBCs do not have a nucleus,
mitochondria, or endoplasmic reticulum, they do have
cytoplasmic enzymes that are capable of metabolizing
glucose and forming small amounts of adenosine
triphosphate (ATP)
 These cytoplasmic enzymes:
o Maintain pliability of the cell membrane
o Maintain membrane transport of ions
o Keep the iron of the cells’ hemoglobin in the ferrous
form (Fe2+) rather than ferric form (Fe3+)
o Prevent oxidation of the proteins in the RBCs
 The metabolic system of old RBCs become progressively
less active and the cells become more and more fragile,
presumably because their life processes wear out
 Once the RBC membrane becomes fragile, the cell ruptures
during passage through some tight spot of the circulation
 Many of the RBCs self-destruct in the spleen, where they
squeeze through the red pulp of the spleen.
o The spaces between the structural trabeculae of the
red pulp, through which most of the cells must pass,
are only 3 micrometers wide, in comparison with the 8
micrometer diameter of the RBC
 Unique structural features & functional demands of RBCs:
GROUP 2 & GROUP 7
o No nucleus: The absence of nucleus means they
cannot undergo protein synthesis, cell division, or
repair damaged cellular components. Without the
ability to regenerate or repair themselves, red blood
cells become more susceptible to wear and tear over
time.
o No mitochondria: RBCs rely exclusively on glycolysis
for energy (a process that does not require oxygen).
The constant expenditure of energy, coupled with the
inability to generate new ATP through oxidative
phosphorylation, contributes to the eventual decline in
the cell’s function.
o No endoplasmic reticulum: The endoplasmic
reticulum is involved in protein synthesis, folding, and
transport within the cell. Since RBCs do not synthesize
new proteins once they mature, they do not require the
endoplasmic reticulum.
o Constant circulation and mechanical stress: RBCs
circulate continuously through the bloodstream
encountering various stresses such as turbulence in
the heart, narrow capillaries, and vessel bifurcations.
The mechanical stress experienced during circulation
contributes to the gradual degradation of the cell
membrane and other structal elements.
o Accumulation of damage: Over time, RBCs
accumulate damage to their cell membranes,
hemoglobin molecules, and other essential
components.
RBC SENESCENCE MARKERS/TAGGING
 No single signal but rather that macrophages recognize
several
 Whatever the signal, macrophages are able to recognize
senescent cells and distinguish them from younger cells;
thus the older cells are targeted for ingestion and lysis.
 CD47 (integrin-associated protein) - protein expressed
on the surface of RBCs
o Decreased expression of CD47 is associated with the
recognition and removal of senescent RBCs by
macrophages
o May also be involved by binding thrombospondin-1,
which provides an “eat me” signal to macrophages
 Phosphatidylserine exposure - considered a signal for
macrophages to recognize and phagocytose senescent
RBCs
 Band 3 clustering - a major protein in the RBC membrane
o The clustering of band 3 is associated with RBC aging,
and its recognition by macrophages can lead to
phagocytosis
 Glycophorins and other membrane proteins - changes
in the glycosylation patterns of membrane proteins, such as
glycophorins can serve as markers for RBC senescence
 Autoantibodies and Immunoglobulin G (IgG) binding -
binding of autologous IgG antibodies to RBC surface
proteins, particularly band 3, can mark RBCs for removal by
the immune system
 Eryptosis - non-nucleated cell version of apoptosis
(erythrocyte death) that is precipitated by oxidative stress,
energy depletion, and other mechanisms that create
membrane signals that stimulate phagocytosis.
o Considered a form of programmed cell death for RBCs
ROLES OF SPLEEN & LIVER IN THE CLEARANCE
OF SENESCENT RBC
 When RBCs burst and release their hemoglobin, the
hemoglobin is phagocytized almost immediately by
macrophages in many parts of the body, but especially by
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 TRANS: Module 14
the Kupfer cells of the liver and macrophages of the
spleen and bone marrow.
 Liver: The Kupfer cells remove senescent blood cells from
circulation
o Kupfer cells - specialized macrophages located in the
sinusoids of the liver whose primary function is to
phagocytose pathogens, cellular debris, and
senescent RBCs.
 Spleen: Macrophages also engulf senescent RBCs and
breaks them down
o Macrophages in the spleen are able to recognize
senescent cells and distinguish them from younger
cells, thus the older cells are targeted for ingestion
through phagocytosis
DEGRADATION OF HEMOGLOBIN & RECYCLING OF
IRON
 Senescent or damaged RBCs are phagocytosed by
macrophages of the reticuloendothelial system (RES)
present in the spleen and liver
 Within the macrophage, heme derived from hemoglobin is
converted by the enzyme heme oxygenase to biliverdin,
releasing carbon monoxide and iron as by-products
 Iron released from heme is exported from phagocytic
vesicles in the macrophage by NRAMP 1 (natural
resistance-associated macrophage protein 1)
 Iron is subsequently secreted into the circulation by the
transmembrane protein ferroportin
o Ferroportin plays a central role in both iron absorption
by the intestine and iron secretion from macrophages
 In the blood, ferrous (Fe2+) is oxidized to ferric form (Fe3+)
in a reaction catalyzed by the ferrioxidase ceruloplasmin
o Ceruloplasmin - copper containing plasma enzyme
synthesized by liver
 Once oxidized, Fe3+ is then bound to transferrin in blood
 The iron released from macrophages in this way (25 mg/d)
is recycled, thereby reducing the need for intestinal iron
absorption, which averages only 1-2 mg/d
 During the next few hours to days, the macrophages
release iron from the hemoglobin and pass it back into the
blood, to be carried by transferring either to the bone
GROUP 2 & GROUP 7
marrow for the production of new RBCs or to the liver and
other tissues for storage in the form of ferritin
 The porphyrin portion of the hemoglobin molecule is
converted by the macrophages, through a series of stages,
into the bile pigment bilirubin, which is released into the
blood and later removed from the body by secretion through
the liver into the bile
o The enzyme biliverdin reductase reduces the central
methylene bridge of biliverdin to a methyl group,
producing the yellow-pigment bilirubin
RED CELL ANTIGENS & RESPECTIVE PLASMA
ANTIBODIES
MAJOR RED CELL SURFACE ANTIGENS &
CORRESPONDING BLOOD TYPES
 Blood is made up of red blood cells, white blood cells and
platelets in a liquid called plasma.
 Your blood group is identified by antibodies and antigens in
the blood.
 Antibodies are proteins found in plasma. They're part of
your body's natural defences. They recognise foreign
substances, such as germs, and alert your immune system,
which destroys them.
 Antigens are protein molecules found on the surface of red
blood cells.
 Blood types are determined by the presence or absence of
certain antigens – substances that can trigger an immune
response if they are foreign to the body. Since some
antigens can trigger a patient's immune system to attack the
transfused blood, safe blood transfusions depend on
careful blood typing and cross-matching.
 The major red cell surface antigens refer to specific
molecules or markers present on the surface of red blood
cells.
 These antigens play a crucial role in blood transfusions and
are important considerations in blood compatibility.
 The two major blood group systems that are commonly
recognized are the ABO system and the Rh system.
o ABO System
o Rh System
 The ABO System, determined by the presence or absence
of two antigens, A and B, on the surface of red blood cells.
 In addition to the A and B antigens, there is a protein called
the Rh factor, involves the Rh factor, also known as the D
antigen.
 A person is classified as Rh-positive (has the D
antigen/present (+) ) or Rh-negative (lacks the D antigen/
absent (-) ), creating the 8 most common blood types (A+,
A-, B+, B-, O+, O-, AB+, AB-).
 GROUP A - has only the A antigen red cells (and B antibody
in the plasma)
 GROUP B - has only the B antigen red cells (and A antibody
in the plasma)
 GROUP AB - has both the A and B antigen red cells (and
neither A nor B antibody in the plasma)
 GROUP O - has neither A nor B antigen red cells (but both
A and B antibody are in the plasma)
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 TRANS: Module 14

 Degree of hemoglobinization, reflected in the color of

red cells (normochromic or hypochromic) – which could
be determined by your MCHC value
 Shape - could be assessed through visual inspection of
blood smears

ABSOLUTE VS RELATIVE ANEMIA

 Absolute Anemia - refers to a true decrease in the number
of red blood cells or the amount of hemoglobin in the blood.
 Relative Anemia - a situation where the concentration of
red blood cells or hemoglobin appears low, but the actual
number of red blood cells is normal. This can occur when
there is an expansion of blood volume without a
proportional increase in red blood cell mass.

POLYCYTHEMIA
ANTIBODIES IN EACH BLOOD TYPE / ANTIGEN- CAUSE OF PHYSIOLOGIC POLYCYTHEMIA
ANTIBODY REACTIONS BETWEEN DIFFERENT  Most common cause of secondary polycythemia
BLOOD TYPES  Occurs in those who live at altitudes of 14,000 to 17,000
 Blood Type A: feet
o Antigens on Red Blood Cells: A  Atmospheric oxygen is very low
o Antibodies in Plasma: Anti-B antibodies  Blood count: 6 to 7 million/mm3
o Reaction to incompatible blood:
 Reacts with: Type B blood
 Outcome: Anti-B antibodies in the recipient's
RBC Count: 6 to 7 million/mm3
plasma will react with the B antigens on the
donor's red blood cells, leading to agglutination Hematocrit: 30%
(clumping) and potential harm to the recipient.
 Blood Type B:
o Antigens on Red Blood Cells: B ABSOLUTE VS RELATIVE POLYCYTHEMIA
o Antibodies in Plasma: Anti-A antibodies  Relative - hemoconcentration due to decreased plasma
o Reaction to incompatible blood: volume
 Reacts with: Type A blood o results from dehydration (deprivation of water,
 Outcome: Anti-A antibodies in the recipient's prolonged vomiting or diarrhea, or excessive use of
plasma will react with the A antigens on the diuretics)
donor's red blood cells, causing agglutination and  Absolute
potential complications.
 Blood Type AB: RELATIVE ABSOLUTE
o Antigens on Red Blood Cells: A and B
 Increase in the total red
o Antibodies in Plasma: None (lacks anti-A and anti-B  Hemoconcentration
antibodies) blood cell
due to decreased
o Reaction to incompatible blood: plasma volume  2 types: Primary and
 Secondary
Reacts with: None (can receive A, B, AB, or O  Results from
blood without an immune response) dehydration
 Outcome: Blood type AB is considered the (deprivation of water,
universal recipient, as it lacks the antibodies that prolonged vomiting
would react with A or B antigens. or diarrhea, or
 Blood Type O: excessive use of
o Antigens on Red Blood Cells: None diuretics)
o Antibodies in Plasma: Anti-A and anti-B antibodies  Associated with
o Reaction to incompatible blood: stress polycythemia
 Reacts with: Type A, B, and AB blood or Gaisböck
 Outcome: Anti-A and anti-B antibodies in the syndrome, a
recipient's plasma will react with the A or B condition of unknown
antigens on the donor's red blood cells, leading to etiology
agglutination and potential complications.  Males are usually
affected
ANEMIA & POLYCYTHEMIA (hypertensive, obese,
ANEMIA and anxious
 Anemia - defined as a reduction of the total circulating red (“stressed”)
cell mass below normal limits such as reduction of
hematocrit and hemoglobin concentrations

DETERMINANTS OF ANEMIA
 Red cell size (normocytic, microcytic, or macrocytic) -
which is determined by the MCV value

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PRIMARY VS SECONDARY POLYCYTHEMIA

Primary Secondary
(Low Erythropoietin) (High Erythropoietin)
 Results from an  Stems from the
intrinsic abnormality response of red cell
of hematopoietic progenitors to elevated
precursors levels of erythropoietin
 Much less commonly,  Erythropoietin-
results from familial secreting tumors and
erythropoietin rare (but illustrative)
receptor mutations inherited defects in
that induce various components of
erythropoietin- the renal oxygen-
independent receptor sensing pathway
activation  Defects stabilize HIF-
 Polycythemia vera is 1α, a transcription
the most common factor that stimulates
cause the transcription of the
erythropoietin gene
 Elevated hematocrit
leads to increased
blood viscosity and
sludging
 Physiological
polycythemia is the
most common cause

 Polycythemia vera - myeloproliferative neoplasm

associated with mutations that lead to erythropoietin-
independent growth of red cell progenitors
o Characterized by increased marrow production of red
cells, granulocytes, and platelets (panmyelosis), but it
is the increase in red cells (polycythemia) that is
responsible for most of the clinical symptoms
 Pathogenesis: In PCV, the transformed progenitor cells
have markedly decreased requirements for erythropoietin
and other hematopoietic growth factors due to activating
mutations in the tyrosine kinase JAK2
 JAK2 - participates in the JAK/STAT pathway
o lies downstream of multiple hematopoietic growth
factor receptors, including the erythropoietin receptor
o Because the pathway is constitutively active and red
cell numbers are abnormally high, serum erythropoietin
levels in PCV are low

RBC Count: 7 to 8 million/mm3

Hematocrit: 60% to 70%

GROUP 2 & GROUP 7 19