HEMATOLOGY 311 nels

MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,

MEMBRANE STURCTURE, AND FUNCTION
✓ Deformable and tolerant against mechanical stress and various
pH and salt concentrations in vivo and in vitro.
Figure 1.0
• Primary blood cell, circulating at 5 million RBCs/uL of blood Note: Horizontal interaction supports everything on the
• Mature RBCs size from 6-8 micron (ave. of 7.5 in diameter), RBC membrane.
average volume of 90 fL A. MEMBRANE LIPIDS
• Has no nucleus nor organelles (anucleate cells) OUTER LAYER
• Exists in blood circulation for 120 days (in a healthy individuals). o Phosphatidyl choline
• Limited activity to metabolize fatty acids and amino acids o Sphingomyelin
• Metabolic processes are maintained through different INNER LAYER
metabolic pathways to produce energy (in order to
survive the 120 days, we’ll be needing these metabolic
pathways to produce RBC).
a. Embden-Meyerhof (production of ATP within cytoplasm)
-Major pathway
b. Oxidative / Hexose-Monophosphate shunt
c. Methemoglobin reductase
d. Leuberin-Rapoport/Rapoport leuberin
Note: The function of RBC membrane is to maintain the cell shape
and deformability, maintains osmotic balance, act as a supporting
skeletal system, and for transportation.

RETICULOCYTE MEMBRANE
✓ Young reticulocytes are less stable than those of mature cells
(because they are immature). o Phosphatidyl ethanolamine
✓ Possesses a significant amount of tubulin and actin o Phosphatidyl serine
-Tubulin and actin are important during the terminal erythroid B. MEMBRANE PROTEINS
differentiation in terms of cell division and cell motility. (RBC INTEGRAL PROTEINS (TRANSMEMBRANE PROTEIN)
does not have this) o Band 3 (anion exchanger protein)
✓ Transition to mature RBCs has significant changes o Glycophorin A, B, C, D
o Increase in shear resistance o Aquaphorin
o Loss of surface (about 20%) area due to loss of membrane PERIPHERAL PROTEINS
lipid o Spectrin
o Acquisition of a biconcave shape -Alpha and beta
-RBC has a biconcave shape -Responsible for the biconcave shape of RBC
o Loss of cytoplasmic organelles o Actin
o Undergoes active endocytosis and exocytosis which does o Protein 4.1
not occur in mature RBCs o Pallidin (band 4.2)
MATURE RBC MEMBRANE
o Ankyrin
✓ Constantly changes as it moves through the circulation
o Adducin
✓ Soft and pliable (pliable: flexible)
o Tropomycon
-Its flexible because it does not have the nuclei. RBC must be
o Tropomodulin
soft and pliable so that it can pass through the tiny capillaries to
carry the oxygen.
✓ Biconcave shape
-Biconcave so that it will be able to pass through the small • Phospholipids form an impenetrable fluid barrier as
capillaries and carry the oxygen. their hydrophilic polar head groups are arrayed
✓ Consists of a membrane skeleton protein lattice and lipid upon the membrane’s surfaces
bilayer • Their hydrophobic nonpolar acyl tails arrange
o 52% glycoproteins themselves to form a central layer dynamically
o 40% lipids mostly phospholipids, cholesterol sequestered (hidden) from the aqueous plasma
o 8% carbohydrate linked to lipid or protein
-The carbohydrates occurs on the external surface of the and cytoplasm.
red cells. 1. Cholesterol
-Lipids: Internal and External layers. − Confers tensile strength to the lipid bilayer
-Protein: Peripheral and Integral proteins. − Esterified and largely hydrophobic, resides
*The peripheral protein interacts to form a cytoskeleton. parallel to the acyl tails of the phospholipids,
*The integral protein penetrates the lipid bilayer and are equally distributed between the outer and inner
firmly anchored within. layers.
✓ More than 50 transmembrane proteins have been identified − Evenly dispersed within each layer,
and more than half carries blood group antigens. approximately one cholesterol molecule per
Reference: Mrs. Agnes Guzman, RMT
 HEMATOLOGY 311 nels
MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
phospholipid molecule.
− Cholesterol’s b-hydroxyl group, the only
hydrophilic portion of the molecule, anchors
within the polar head groups.
2. Phospholipids
− Are asymmetrically distributed (Outer:
Phosphatidyl choline & sphingomyelin; Inner:
phosphatidyl choline phosphatidyl serine).
− The energy of these four are energy dependent,
relying on a number of membrane-associated
enzymes (flippases, floppases, scramblases) for
their positions.
− When phospholipid distribution is disrupted, as
in sickle cell anemia and thalassemia, the only
negatively charged phospholipid redistributes to
the outer layer.
3. Glycolipids (sugar-bearing lipids)
✓ Associate in clumps or rafts and support
carbohydrate side chains that extend into the
aqueous plasma to anchor the glycocalyx
(glycocalyx - a layer of carbohydrates whose net
negative charge prevents microbial attack and
protects the RBC from mechanical damage
caused by adhesion to neighboring RBCs or to
the endothelium)
• Although cholesterol and phospholipids
constitute the principal RBC membrane
structure, transmembrane (integral) and
cytoskeletal (skeletal, peripheral) proteins
make up 52% of the membrane structure by
mass.
TRANSMEMBRANE PROTEINS
BAND 3
✓ Anion transport: mediates chloride-bicarbonate exchange.
✓ Provides a binding site for glycolytic enzyme, hemoglobin,
and skeletal protein
✓ Linkage of lipid bilayer to underlying membrane skeleton.
(serves as junction)
-Interaction with ankyrin and protein 4.2, secondarily
through binding to protein 4.1. (tingin ka sa figure 1.0)
-Main importance is for prevention of surface loss.
GLYCOPHORIN
✓ Cyanic acid which gives RBC a very hydrophilic charge.
✓ Receptor for plasmodium
✓ Plays an important part in the invasion of RBC by malarial
parasites.
✓ Imparts a negative charge to the cell
✓ Glycophorin A = carries peptide-defined MN (M and N
determinants), Gerbich blood group antigens
✓ Glycophorin C, Glycophorin A = important for P.falciparum
invasion and development in RBC
✓ Glycophorin B = carries Ss determinants
AQUAPORIN 1
✓ Selective pores for water transport
✓ Allows RBC to remain in osmotic equilibrium with
extracellular fluid.
-Everything should be balance to avoid cell shrinking or
swelling.
Reference: Mrs. Agnes Guzman, RMT
✓ Major function: water transport
RBC MEMBRANE SKELETON (CYTOSKELETAL PROTEINS)
✓ Hexagonal lattice with 6 spectrin molecules
✓ Each linked to multiple spectrin tetramers
✓ Composed of Spectrin, Actin, Protein 4.1
✓ Ankyrin links the lipid bilayer to membrane via interaction
with band 3.
SPECTRIN
✓ Flexible, rod-like molecule
✓ Responsible for biconcave shape of RBC
✓ Is
✓ Two sub-units (Alpha and Beta)
✓ Beta spectrin:
o Attachment for ankyrin near C terminus (which
binds cytoplasmic tail of band 3) thus
attachment of skeleton to lipid bilayer
At N terminus:
o Attachment for protein 4.1 (associated with glycophorin
C)
-Second anchor point with lipid membrane
o Binding sites for actin filaments and protein
4.1 – forming a junctional complex
-The secondary structure of both a- and b-
spectrin features triple-helical repeats of 106
amino acids each; 20 such repeats make up
a-spectrin, and 16 make up b-spectrin.
-Single helix at the amino terminus of a-
spectrin consistently binds a pair of helices at
the carboxyl terminus of the b-spectrin chain,
forming a stable triple helix that holds
together the ends of the heterodimers.
ACTIN
✓ Short, uniform filaments
✓ Length modulated by
tropomyosin/tropomodulin
✓ Approximately 6 spectrin ends interface with
one actin filament stabilized by protein 4.1.
Remember:
-If there’s a deformability, there’s a problem with the
carbohydrate, protein, or lipids.
-Poikilocytosis: variation of the shape of RBC.
-Anisocytosis: variation of the size of RBC.
-If there’s a problem with the shape, it signifies
membrane defects which includes the spectrin, ankyrin,
protein, lipids, and carbohydrates.
Other peripheral proteins:
PROTEIN 4.1
✓ Stabilizes actin-spectrin interactions
ADDUCIN
✓ Also stabilizes interaction of spectrin with actin.
✓ Influenced by calmodulin (calcium binding protein)
-Promotes spectrin-actin interactions
ANYKRIN
✓ Interacts with band 3 and spectrin to achieve
linkage between bilayer and skeleton
✓ Augmented by protein 4.2
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MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
-Plastic deformation: process in which permanent
deformation is caused by sufficient load. It produces a
permanent change in which would lead to size and shape
alterations.
✓ Deformability can be reduced by increases in associations
between skeletal proteins or between skeletal and integral
(esp. band 3) proteins.
Note:
-RBC should reach its 120 days life span through the help of the 4
metabolic pathways.
-These pathways are important because these are the RBC’S source
of energy.
CYTOPLASMIC CHARACTERISTICS
✓ Cytoplasmic contents of RBCs include: potassium ions,
sodium ions, glucose, intermediate products of glycolysis and
enzymes
✓ Embden-Meyerhof pathway utilizes 90% of RBC total glucose
✓ Efficient cellular metabolism depends on long-lived enzymes

• Deformability is an important property of red cell

function; it depends not only on RBC geometry but
also on relative cytoplasmic viscosity Influenced by:
o Cell shape (ratio of cell surface area to cell
volume)
-There are instances wherein the surface area
differs from the volume leading to bursting,
shrinking or swelling.
-Could be checked using Osmotic fragility test.
o Cytoplasmic viscosity (regulated by MCHC which
is part of the indices and thus cell volume) • Lacking mitochondria, the RBC relies on anaerobic glycolysis
o Membrane deformability and stability for its energy. Hematologists have identified hereditary
deficiencies of nearly every glycolytic enzyme, and their
CELL SHAPE common result is shortened RBC survival, known collectively
✓ Biconcave disc shape creates an advantageous surface area/ as hereditary non-spherocytic hemolytic anemia.
volume relationship. • Glucose enters the RBC without energy expenditure via the
-Biconcave so that it’ll be able to pass on the thinnest, transmembrane protein Glut-1.
narrowest or smallest blood vessel and capillaries and carry
oxygen. ENERGY METABOLISM IN THE ERYTHROCYTE:
✓ Facilitates deformation while maintaining constant surface
area.
✓ Progressive loss of intracellular and membrane components
results in biconcave shape and improved deformability.
✓ SA/V ratio (surface area) alterations will result in more spherical
shape with less redundant surface area, and thus less capacity
for deformability and diminished survival.
-Ulit, kapag abnormal yung shape, magreresult sa shrinkage,
swelling or bursting.
✓ Membrane loss = reduced SA;
✓ Increase in cell water content = increased volume
-If the cell could not take the increased water volume, it will
lead to bursting or lysis.
-Osmotic fragility test will indicate the threshold of the RBC to
hold sole concentrations. Pag kaya, di magbburst.
-Seen after 2 hours of osmotic fragility testing.

MEBRANE DEFORMABILITY/STABILITY EMBDEN-MEYERHOF PATHWAY

✓ During pressure upon RBC, spectrin molecules undergo
reversible change in conformation: some uncoiled and
extended, others compressed and folded.
✓ During extreme or sustained pressure, membrane exhibits
permanent “plastic” deformation.
Reference: Mrs. Agnes Guzman, RMT
✓ Major source of essential cellular energy.
✓ Main idea: Glucose undergoes conversion or glycolysis
(glucose to lactate/lactic acid) to form 2 ATPs.
-Without ATP (absence/deficiency) a premature cell death
will occur due to inherited defects in glycolysis.
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MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
-2 ATP’s will be the source of energy of the RBC.
✓ Maintains pyridine nucleotides in a reduced state to permit
their function in oxidation-reduction reactions within a cell.
✓ Deficiencies to production of ATP can be exhibited by:
-Premature cell death due to inherited defects in
glycolysis.
-Loss of viability during the stage of blood for transfusions
(blood in blood bags deteriorates in terms of the shape.
remember that as the blood ages, the shape will be altered -Pyruvate may diffuse from the erythrocyte or may become a
from discocyte to spherocyte). substrate for lactate dehydrogenase with regeneration of the
✓ Anaerobic glycolysis (90% glycolysis), the EMP, requires oxidized form of nicotinamide adenine dinucleotide (NAD1).
glucose to generate ATP, a high-energy phosphate source. -The ratio of NAD1 to the reduced form (NADH) modulates
✓ Through the EMP, glucose is catabolized to pyruvate (pyruvic the activity of this enzyme.
acid), consuming two molecules of ATP per molecule of *Three alternate path pathways, called diversions or shunts,
glucose and maximally generating four molecules of ATP per branch from the glycolytic pathway:
molecule of glucose, for a net gain of two molecules of ATP.
-The first phase of glycolysis employs glucose
phosphorylation, isomerization and diphosphorylation to
yield fructose 1,6-biphosphate.
-Fructose-biphosphate aldolase cleaves F1,6-BP to
produce glyceraldehyde -3-phosphate.
-The initial hexokinase and 6-phosphofructokinase steps
consume a total of 2 ATP molecules and limit the rate of
glycolysis.
OXIDATIVE PATHWAY/HEXOSE MONOPHOPHATE SHUNT/AEROBIC
GLYCOLYSIS PATHWAY
✓ 10% Aerobic glycolysis
✓ Main idea: This will provide a reduced glutathione.
-We need to reduce glutathione to prevent the oxidative
denaturation of the hemoglobin.
-If it’s not prevented, it will cause the production of the heinz
bodies (inclusion bodies that can be found on the RBC. it is
seen on the peripheral blood smear of patients with
conditions like G6PD which is the most common RBC enzyme
-The second phase of glucose catabolism converts G3P to 3-
deficiency).
phosphoglycerate (3-PG).
-Normal RBC DOES NOT CONTAIN HEINZ BODIES (or any
-In the first step, G3P is oxidized to 1,3 bisphosphoglycerate (1,3-
inclusion bodies such as pappenheimer, howell jolly, cabot
BPG) through the action of glyceraldehyde-3-phosphate
ring, basophilic stippling)
dehydrogenase (G3PD).
✓ Oxidative catabolism of glucose with reduction of NADP
-1,3-BPG is dephosphorylated by phosphoglycerate kinase, which
(Nicotinamide adenine dinucleotide phosphate) to NADPH
generates 2 ATP molecules and 3-phosphoglycerate (3-PG)
(reduced form of NADP) which is required to reduce
glutathione.
✓ Pathway’s activity is increased with oxidation of glucose with
increased oxidation of glutathione.
✓ If pathway is defective, amount of reduced glutathione
becomes insufficient to neutralize oxidants – causes
denaturation of globin (Heinz bodies).
✓ The HMP detoxifies peroxide (H2O2), which arises from O2
reduction in the cell’s aqueous environment, where it oxidizes
and destroys heme iron, proteins, and lipids, especially lipids
-The third phase of glycolysis converts 3-PG to pyruvate and
containing thiol groups.
generates ATP.
✓ By detoxifying peroxide, the HMP extends the functional life
-The product 3-PG is isomerized by phosphoglycerate mutase to 2-
span of the RBC.
phosphoglycerate (2-PG). Enolase (phosphopyruvate hydratase) then
-The HMP diverts glucose-6-phosphate (G6P) to ribulose 5-
converts 2-PG to phosphoenolpyruvate (PEP).
phosphate by the action of glucose-6-phosphate
-Pyruvate kinase (PK) splits off the phosphates, forming 2 ATP
dehydrogenase (G-6-PD).
molecules and pyruvate. PK activity is allosterically modulated by
-In the process, oxidized nicotinamide adenine dinucleotide
increased concentrations of F1,6-BP, which enhances the affinity of
phosphate (NADP) is converted to its reduced form
PK for PEP. Thus, when the F1,6-BP is plentiful, increased activity of
(NADPH). NADPH is then available to reduce oxidized
PK favors pyruvate production.
glutathione (GSSG) to reduced glutathione (GSH) in the
presence of glutathione reductase
• Glutathione is a cysteine-containing tripeptide, and the
Reference: Mrs. Agnes Guzman, RMT
 HEMATOLOGY 311 nels
MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
designation GSH highlights the sulfur in the cysteine moiety. ✓ Acidic pH and low concentrations of 3-PG and 2-PG inhibit the
activity of bisphosphoglycerate mutase, thus inhibiting the
METHEMOGLOBIN REDUCTASE PATHWAY shunt and retaining 1,3-BPG in the EMP.
✓ Main idea: Maintains the hemoglobin iron in its ferrous state ✓ These conditions and decreased ATP activate
to become functional (carry oxygen). bisphosphoglycerate phosphatase, which returns 2,3-BPG to
-If it turns into a ferric state, in won’t be functional anymore the glycolysis mainstream.
because it won’t be able to carry oxygen. ✓ In summary, these conditions favor generation of ATP by
✓ Depends on Embden-Meyerhof pathway for the reduced causing the conversion of 1,3-BPG directly to 3-PG and
pyridine nucleotides that keeps Hgb in reduced state. returning 2,3-BPG to 3-PG for ATP generation downstream by
✓ Methemoglobin is a derivative/modified type of hemoglobin. PK.
✓ Prevent the oxidation of heme iron. METABOLIC COMMON ENZYME MAIN IDEA
-Requires the reducing action of NADH and the enzyme PATHWAY DEFICIENCY
methemoglobin reductase. Embden- Pyruvate kinase Maintains cellular
✓ Heme iron is constantly exposed to oxygen and peroxide. Meyerhof deficiency (PKD) energy by generating 2
✓ Peroxide oxidizes heme iron from the ferrous (+2) to the ATP.
ferric (+3) state.
Oxidative/ Glucose-6-phosphate Provides reduced
✓ The affected hemoglobin molecule is called methemoglobin.
Hexose- dehydrogenase (G6PD) glutathione to prevent
✓ Although the HMP prevents hemoglobin oxidation by
Monophosphate hemoglobin
reducing peroxide, it is not able to reduce methemoglobin
shunt denaturation to avoid
once it forms. NADPH is able to do so, but only slowly.
the production of Heinz
-The reduction of methemoglobin by NADPH is rendered
bodies.
more efficient in the presence of methemoglobin
Methemoglobin Maintain hemoglobin
reductase, also called cytochrome b5 reductase.
reductase iron to ferrous state to
✓ Using H1 from NADH formed when G3P is converted to 1,3-
be functional.
BPG, cytochrome b5 reductase acts as an intermediate
Leubering- It will generate 2,3-
electron carrier, returning the oxidized ferric iron to its
Rapoport diphosphoglycerate or
ferrous, oxygen-carrying state.
2,3-DPG which will
✓ This enzyme accounts for more than 65% of the
regulate the
methemoglobin- reducing capacity within the RBC.
hemoglobin affinity to
the oxygen.
LEUBERING-RAPOPORT PATHWAY
✓ Important in the oxygen-carrying capacity of RBCs.
Notes:
✓ Main idea: It will generate 2,3-diphosphoglycerate or 2,3-
DPG which will regulate the hemoglobin affinity to the • ERYTHROKINETICS: term describing the dynamics of RBC
oxygen. production and destruction.
-2,3 DPG is found on the hemoglobin • ERYTHRON: name given to the collection of all stages of
✓ This mechanism is low in energy consumption erythrocytes throughout the body, developing precursor in the
✓ Capable of regulating oxygen transport even with hypoxia BM and the circulating RBC in peripheral blood.
and acid- base disorders. -It conveys the concept of a unified functional tissue. The
✓ Permits accumulation of 2,3-DPG. erythron is distinguished from the RBC mass. The erythron is
✓ Increased in deoxyhemoglobin results to binding 2,3-DPG the entirety of erythroid cells in the body, whereas the RBC
which stimulate glycolysis. mass refers only to the cells in circulation.
-Deoxyhemoglobin is normal but contains an unregulated • HYPOXIA: the stimulus to Red Blood Cell production; Hypoxia,
hemoglobin (very little amount). too little tissue oxygen, is detected by the peritubular cells
✓ A third metabolic shunt generates 2,3- (primary oxygen-sensing system), which produce erythropoietin
bisphosphoglycerate (2,3-BPG; also called 2,3- (EPO), the major stimulatory cytokine for RBCs.
diphosphoglycerate or 2,3-DPG).
✓ 1,3-BPG is diverted by bisphosphoglycerate mutase to ERYTHROPOIETIN
form 2,3-BPG. ✓ A hormone produced in the kidney in response to tissue
-2,3-BPG regulates oxygen delivery to tissues by competing with hypoxia.
oxygen for the oxygen-binding site of hemoglobin. -EPO is released because oh hypoxia
-When 2,3-BPG binds heme, oxygen is released, which enhances ✓ Consists of a carbohydrate unit that reacts specifically with
delivery of oxygen to the tissues. RBC receptors and a terminal sialic acid unit, which is
✓ This diversion of 1,3-BPG to form 2,3-BPG sacrifices the necessary for biological activity in vivo.
production of two ATP molecules. There is further loss of two ✓ Specific action of EPO:
ATP molecules at the level of PK, because fewer molecules of -Induces committed progenitor cells in the bone marrow
PEP are formed. to differentiate and proliferation into pronormoblast.
✓ Because two ATP molecules were used to generate 1,3-BPG and -Shortens the generation time of pronormoblast. (to avoid
production of 2,3-BPG eliminates the production of four hypoxia)
molecules, the cell is put into ATP deficit by this diversion. -Promotes the early release of reticulocytes to the

Reference: Mrs. Agnes Guzman, RMT

 HEMATOLOGY 311 nels
MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
peripheral blood. attach itself to the cells and induce lysis.
-Has something to do with Ag-Ab reaction.
\ • Hemoglobin denaturation = when Hgb is exposed to oxidant
stress and the mechanism to protect the cell from such damage
fails to work, denatured Hgb precipitates forming inclusion
bodies known as Heinz bodies (abnormal inclusion bodies).
-Oxidative pathway is involved.
-Heinz bodies could either contain RNA or DNA.
-WBC also have abnormal inclusion bodies like the RBC.

2 TYPES OF DESTRUCTION:
• INTRAVASCULAR HEMOLYSIS
✓ Lysis of erythrocytes which occurs within the circulation
through the classic pathway.
Summary: Once the tissue hypoxia stimulates/signals the release ✓ Hemolysis: lysis of RBC
EPO from the peritubular fibroblast of the kidney, and it will go to ✓ It is the usual outcome of sensitization of erythrocytes with
the blood flow then the bone marrow. Not all the EPO that will be complement;
accepted by the bone marrow but only those with receptors. Once, -10% of aged/senescent red cell undergo the destruction
the EPO has its receptor, it will penetrate the bone marrow. Then, -EVENTS:
the EPO and the red cells from the bone marrow will stimulate the  RBCs break down in the circulation
release of RBC production in the blood circulation to stop hypoxia.  Free Hgb; binds to haptoglobin, oxidized to
-Remember that RBC is the carrier of oxygen so tissue hypoxia methemoglobin.
(decreased oxygen) will be prevented.  Heme recovered from haptoglobin, albumin or hemopexin
-If the kidney, can’t produce EPO (due to kidney disease), there is (formed from methemoglobin)
this last resort which is through injecting that is used by patients  Bilirubin conjugated by hepatocytes, then excreted as
who have end stage renal disease (ESRD) or those patients who does urobilinogen and bilirubin
not want blood transfusions. But, the release/increase of EPO is CAUSES:
gradual unlike the natural way which is faster. ▪ ABO mismatched blood transfusion
-Patients with ESRD automatically have anemia. -Easiest but most critical because one wrong mistake or
release may have grave repercussions.
ELEVATED EPO LEVELS ARE OBSERVED IN: -Some ag-ab are slow reacting so wait for it.
o Erythroid hyperplasia -Mix it well for slide method.
o Polycythemia ▪ Cold agglutinin disease
o Hemorrhages ▪ Burns
o Inc. RBC destruction -Especially 3rd degree burns
▪ Snake bites
DECREASE EPO LEVELS: ▪ Bacteria – C. perfringens sepsis
o Anemia ▪ Parasite – P. malaria
-Not a disease but a manifestation of certain disease or -Plasmodium parasites will go inside the RBC that will lead to
condition. cell burst or lysis.
-Ex: ESRD, Patients with metabolic problems ▪ Mechanical heart valves
-Anemia may be caused by increased destruction of RBC, ▪ Paroxysmal cold hemoglobinuria (PCH)
blood loss, or the bone marrow is unable to produce RBC. -Some antibodies are responsible for this.
-RBC tends to lyse during cold weather.
-Urine color: amber/tea color
▪ Paroxysmal nocturnal hemoglobinuria
• Fragmentation = loss of a portion of the erythrocytes -Some antibodies are responsible for this.
membrane, accompanied by loss of cellular contents, including -RBC tends to lyse at night.
hemoglobin. -Urine color: amber/tea color
-Breaks into pieces
• Osmotic Lysis = passing of water into the red cell as to
ultimately burst it.
-Depends on how long your RBC could hold a certain amount of
water. If it exceeds, the cell will burst or undergo lysis.
-Same with malaria because of the infection caused by
plasmodium (plasmodium parasites) will enter the RBC and will
lead to cell bursting.
• Erythrophagocytosis = ingestion of whole red cells by
circulating monocytes or neutrophil or by fixed macrophages of
the mononuclear phagocyte system.
• Complement induced cytolysis = complement has the ability to
Reference: Mrs. Agnes Guzman, RMT
 HEMATOLOGY 311 nels
MIDTERMS WEEK 6: EYTHROCYTE METABOLISM,
MEMBRANE STURCTURE, AND FUNCTION
Summary: There is RBC breakdown/lysis. Since there is lysis the
membrane is already destructed. This destruction will lead to the
leakage of cellular contents. The free hemoglobin will bind to
haptoglobin then it will go to the plasma then the urine. The
presence of hgb in the plasma is called hemoglobinemia while the
presence of hgb in the urine is called hemoglobinuria. The other
hemoglobin which is taken or reabsorbed by the renal tubular cells
will form hemosiderin which is a yellowish-brown crystal like that is
a criterion for lysis.

• EXTRAVASCULAR HEMOLYSIS
✓ Lysis of erythrocytes outside the circulation, in the RES of
the cell liver, spleen.
✓ This usually happens through phagocytosis
✓ About 90% of aged red cells are destroyed
-EVENTS:
 Ingestion of red cells by macrophages in the liver, spleen Summary: The unwell RBC will be ingested by the macrophage. This
and bone marrow RBC will be disrupted then will be separated in parts. The globin will
 Little or no hemoglobin escapes into the circulation be degraded and will go back to the amino acid pool while the iron
 Anemia will bind to transferrin to be carried and recycled by some various
 Decreased Haptoglobin tissues. The protoporphyrin will be degraded to bilirubin then will be
 Normal plasma hemoglobin further degraded to unconjugated bilirubin in which it will be
 RES phagocytosis of RBCs processed in the liver to produce the bilirubin glucuronides. This
 RBC membrane is disrupted bilirubin glucuronides will be converted in the gut and eliminated as
 Lysosomal digestion of Hgb stercobilinogen (faeces) while the other will be reabsorbed by the
 Recovered iron transported to bone marrow kidney and is excreted as urine.
 Protoporphyrin metabolized to bilirubin, conjugated and -2 way release (urine or feces).
excreted.
CAUSES: READ RODAKS PAGE 124.
▪ Some bacterial/Viral infection
▪ Drug induced
-Penicillin can cause the destruction of RBC.
-Should be prescribed by the physician.
▪ Autoimmune
▪ Microangiopathy – Malignancy, Disseminated intravascular
coagulation (DIC), Thrombotic thrombocytopenic purpura
(TTP), Eclampsia
-DIC is a combination of bleeding and clumping.
-TTC is the decrease of platelets
-Eclampsia is seen on pregnant women (BP: 200/160), protein
in the urine is seen. It is crucial for both the mother and
infant. (Remedy: STAT CS)
▪ Hemoglobinopathies
-Sickle cell anemia
▪ Membrane defects – spherocytosis, elliptocytosis,
acanthocytosis (problem on the protein side. Either the
spectrin or actin)
-RBC becomes non-functional
▪ Metabolic defects – G6PD deficiency/ oxidant drugs
-G6PD patients can live a normal life
-Beans should be avoided

Reference: Mrs. Agnes Guzman, RMT