Diff Hemoglobin Derivatives/ Abnormal 1. _____________ - ferric state of blood ➔ Color: _____________ 2. ____________- bound to carbon monoxide which has 210 times greater affinity ➔Color: __________ 3.___________ - exposure to sulfhydryl compounds ➔ ____________

1. Methemoglobin Color: Chocolate brown 2. Carboxyhemoglobin Color: Cherry Red 3. Sulfhemoglobin Color: Mauve-Lavender / irreversible

TOPIC 1: ERYTHROCYTE METABOLISM AND DESTRUCTION Flashcards by Misaki Ayuzawa

CHARACTERISTICS OF A RED BLOOD CELL

Size: ___________

Shape:___________

Lifespan: ___________

Function: __________

Size: 7-8 um, average 7.2 um
Shape: Biconcave Disc
Lifespan: 90-120 Days
Function Efficient transport of oxygen from the lungs
to the tissues, and carbon dioxide from the
tissues to the lungs

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Red blood cells also known as ___________

Erythrocytes

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Diff Hemoglobin Derivatives/ Abnormal

_____________ - ferric state of blood
➔ Color: _____________
____________- bound to carbon monoxide
which has 210 times greater affinity
➔Color: __________

3.___________ - exposure to sulfhydryl compounds
➔ ____________

Methemoglobin
Color: Chocolate brown
Carboxyhemoglobin
Color: Cherry Red
Sulfhemoglobin
Color: Mauve-Lavender / irreversible

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______________ have a very strong plasma membrane

Red Blood Cell

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_____________ - indicates there is little to no
hemoglobin in the area

Central pallor

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Biconcavity
● Most hemoglobin are found on the ___________
● ______ volume
● _________surface area
● _________ cell membrane
● __________ compared to volume

● Most hemoglobin are found on the periphery
● 90 fL volume
● 140um2 surface area
● Very thin cell membrane
● Large surface area compared to volume

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● To separate the intracellular fluid environment from
the extracellular fluid environment

RBC Membrane

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RBC Membrane

_______ Proteins
_______ Lipids (Phospholipids, Cholesterol)
________ Carbohydrates

52% Proteins
40% Lipids (Phospholipids, Cholesterol)
8% Carbohydrates

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● __________ and ________ spectrin ➔ Helical configuration

Alpha and beta

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bound to Band 3 protein

Ankyrin

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anion exchanger

Band 3

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Stabilizes the linkage of ankyrin to band 3

Band 4.2

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_________________ - Transmembrane
○ Gives RBC a negatively charged surface
○ Contains ‘sialic acid

Glycophorin C

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Cytoskeletal protein

SPECTRIN

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➔ Function of cytoskeletal protein

Provides the shape/ maintains the framework of the cell

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Is Protein Interaction Important? YES OR NO?

● Yes
● One absence of the protein will incur damages to the
system

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____________ - there is a problem in the spectrin protein

Hereditary spheocytosis

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the shape of their RBC–instead of biconcave, it
becomes spherical

The name of the cell is called _________ and it doesn’t have __________________

Spherocyte
No Central pallor

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Cells that are spherocytic in shape tend to
_________, leading to ___________

HEMOLYZE - ANEMIA

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EXAMPLES OF TRANSPORTER MEMBRANE PROTEINS
AND FUNCTIONS

Water transporter

Aquaporin 1

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EXAMPLES OF TRANSPORTER MEMBRANE PROTEINS
AND FUNCTIONS

Anion transporter, support
system for surface antigens of
ABHblood group antigens

Band 3
Anion Exchanger 1

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EXAMPLES OF TRANSPORTER MEMBRANE PROTEINS
AND FUNCTIONS

Ca2+ transporter

Duffy blood group
antigens

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Glucose transporter, supports
ABH blood group antigens

GLUTI

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Transports negatively charged
sialic acid, supports MN blood
group antigens

Glycophorin A

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Transports negatively charged sialic acid, supports Ss blood group antigens

Glycophorin B

Transports negatively charged sialic acid, supports Gerbich blood group system antigens

Glycophorin C

Integrin Adhesion

ICAM 4

Zn2+ binding endopeptidase, supports Kell blood group antigens

Kell blood group antigens

Urea transporter

Kidd blood group antigens

Supports Dand CcEe blood group antigens

Rh blood group antigens

Supports DCcEe antigen expression, gas transporter (probably CO2 )

Rh antigen expression protein

IONIC TRANSPORT AND HYDRATION HOMEOSTASIS a Gradient-driven passive or secondary active transporters 1. 2. 3. 4.

○ Band 3 ○ KCC ○ NKCC ○ KNHE

– depends on what is the concentration on the other side of the membrane

Gradient-dependent

____________ -this is why our bones are strong

MINERALIZATION

The membrane will mineralize as well which becomes rigid- which makes it hard to go to the spleen which makes it hard for _______________

RBC destruction

RBC CYTOPLASM 1. 2. 3.

Electrolytes Metabolic Materials Enzymes

○ accurate balance of intracellular K+, Na+ and Ca2+

Electrolytes

○ glucose, intermediate products of glycolysis

● Metabolic Materials

○ glycolytic enzymes

Enzymes

RBC ENERGY METABOLISM ● Limited metabolic activity __________________ (metabolism) - no mitochondria left [only Aerobic if THERE is mitochondria

Anaerobic respiration

is the most immediate source of energy in all cells

Glucose

What hormone is responsible for the entry of glucose into the cell?

Insulin

What electrolye will enter alongside glucose?

Potassium

➔ What glucose needs is

INSULIN

Produces 90% of glucose energy used by RBC

EMBDEN-MEYERHOF PATHWAY

2 molecules of ATP are consumed ● 4 molecules of ATP are produced for each molecule of glucose ● Major energy metabolic pathway in the RBC ● 90% of energy in an RBC is obtained from this pathway ● 4 TOTAL ATP molecules produced; 2 are consumed– 2 net molecules

EMBDEN-MEYERHOF PATHWAY

DIVERSION PATHWAYS

1. Hexose-Monophosphate Pathway 2. Methemoglobin Reductase Pathway 3. Leubering-Rapoport Pathway

also known as Pentose Phosphate Pathway ● Function ➔ Protects hemoglobin from oxidative stress by generating NADPH (product) ○ Important for protection of RBC

1. HEXOSE-MONOPHOSPHATE PATHWAY

- whitening of side effect - OFFERS protection against oxidative stresses - Since it is a reducing substance ; gives production to cells from oxidative stres

Glutathione

provides the only means of generating NADPH for glutathione reduction and in its absence, erythrocytes are particularly vulnerable to oxidative damage

G6PD

G6PD can lead to

HEINZ BODIES

What happens if there is G6PD deficiency? _____________, ____________, __________are not allowed-some medications are not allowed as well

Soy, peanuts, and tomatoes

Appearance: Dots near the periphery on the RBC ○ Normally there should be NOTHING on the RBC

basophilic stipling

A BITE CELL - ___________

POIKILOCYTE

regulation of oxygen release in the tissues ● generation 2,3-Diphosphoglycerate (2,3-DPG)

LUEBERING-RAPOPORT PATHWAY

Where will 2,3-BPG/DPG bind?

The attachment of 2,3-DPG is because of a SALT BRIDGE that forms between the 2 BETA CHAIN

occurs when there is decreased oxygen tension into the tissues → need of oxygen increases

Hypoxia

Mechanism of hypoxia ● ____________ the level of 2,3-GDP ● _____________ in pH

Increase Decrease

The RBC already served its entire lifespan; NORMAL

Senescence

LIFESPAN OF RBC: ________________

90-120 Days

What is the normal way of RBC destruction? ______________ by _________________

ERYPTOSIS by SPLENIC MACROPHAGE

EXTRAVASCULAR HEMOLYSIS Also known as: ____________________ ● Organ location: _______________

MACROPHAGE MEDIATED SPLEEN

◆ RBCs experience slow movement through the red pulp of the spleen, which hinders their circulation. ◆ This sluggish flow causes several problems.

➔ Sluggish movementthrough RED PULP

◆ As RBCs move slowly, the available glucose in the surrounding blood is quickly depleted. ◆ RBCs rely on glucose for glycolysis, which is essential for their energy production

➔ Depletion of Glucose

◆ The low pH in the spleen promotes iron oxidation. Maintaining reduced (ferrous) iron is an energy-dependent process. ◆ Factors that promote iron oxidation cause RBCs to expend more energy, accelerating the catabolism of enzymes.

➔ Low pH

◆ Due to reduced glucose availability and sluggish flow, the glycolytic processes within RBCs deteriorate. ◆ This leads to a reduction in ATP production

➔ Deteriorating Glycolysis

◆ Several membrane systems within RBCs rely on ATP. The reduced ATP production leads to the failure of these systems. For example, enzymes responsible for maintaining the location and reduction of phospholipids in the membrane begin to fail.

➔ ATP-Dependent Systems Fail

____________________ ◆ ATP-dependent enzymes are responsible for maintaining a high level of intracellular potassium while pumping sodium out of the cells. ◆ When this system fails, intracellular sodium levels increase, and potassium levels decrease. ◆ This disrupts the selective permeability of the RBC membrane, causing water to enter the cell

➔ Ion-Imbalance

◆ As a result of the factors mentioned above, the discoid (biconcave) shape of RBCs is lost, and the cells become spherical and rigid

➔ Change in RBC Shape

◆ RBCs must remain highly flexible to exit the spleen by squeezing through the narrow spaces formed by endothelial cells lining the venous sinuses and the basement membrane. ◆ Spherical RBCs are unable to squeeze through these spaces and become trapped against the endothelial cells and basement membrane

➔ Inability to pass through splenic sieve

◆ In this situation, trapped RBCs are readily ingested by macrophages that patrol along the sinusoidal lining. ◆ Macrophages recognize the senescent (aging) RBCs and distinguish them from younger cells. These older cells are targeted for ingestion and lysis.

Phagocytosis

Some researchers view the death of RBCs in the spleen as a form of apoptosis called eryptosis, which is precipitated by factors such as oxidative stress, energy depletion, and membrane signals that stimulate phagocytosis.

Eryptosis

RBCs’ membranes become ___________as they reach senescent.

RIGID

This signals the _______________________to ingest the trapped red blood cells, thus leading to destruction

SPLENIC MACROPHAGE

– SAFEST way that the hemoglobin metabolic waste product to be excreted out of the body. ● There is no hemoglobin that is secreted out of the body. It will have to be processed first

BILIRUBIN METABOLISM

_____________is a colorless product and will be further converted into 2 and these two become part of your stool and urine

UROBILINOGEN Stercobilin ○ Urobilin

Responsible in giving the brown color of stool

STERCOBILIN

Responsible in giving yellow color of urine

UROBILIN

BILIRUBIN 1

→ Unconjugated Bilirubin → Water Insoluble → Non-Polar Bilirubin → Indirect Reacting → OTHER TERM: Hemobilirubin → Free Bilirubin/Slow-reacting → Prehepatic bilirubin

BILIRUBIN 2

→ Conjugated bilirubin → Water-soluble → Polar bilirubin → Direct reacting → Cholebilirubin → One-minute/Prompt Bilirubin → Post hepatic bilirubin