Section 6 - hemolysis

State the length of normal RBC survival in circulation.

~120 days

State the 3 main physiologic functions of the RBC membrane

(Maintain osmotic balance, maintain cell shape and deformability, transport cellular ions and gasses)

1) Maintain osmotic balance between plasma and cell cytoplasm. Compare RBC in isotonic (normal), hypotonic soln (swollen), Hypertonic soln (crenated)

2) Maintain shape and deformability- cells deform to streamline and reduce resistance.

3) Transport cellular ions & gasses: cation pump regulate balance of Na+ & K+

-gasses = O₂ & CO₂

-Anions = HCO3-, Cl-

-Cations = Na+, K+

State the role of sialic acid in the RBC membrane

(negative charge, cellular repulsion)

provides a negative charge to maintain cellular repulsion. Prevents RBCs from clumping together & protects RBC’s from premature detection by immune system.

is an integral protein- goes across lipid bilayer

State the function of Spectrin in the RBC

(Provides cytoskeleton)

Modulates shape and deformability

Embden-Meyerhof Pathway (Metabolic pathway)

(Anaerobic Glycolysis)

RBC major source of cellular energy (90-95% or RBC glucose consumption)

Net gain of 2 ATP

Pyruvate Kinase is one of the most common ENZ deficiencies that affects RBC

Hexose Monophophate Pathway/Shunt (Metabolic pathway)

(Aerobic glycolysis, Oxidative)

How the body fights oxidative injury to RBCs

The main enzyme is Glucose-6-phosphate dehydrogenase (G6PD)

Rapport-Luebering Pathway (Metabolic Pathway)

(Regulates oxygen delivery to the tissues)

2,3,-biphosphglycerate

Methemoglobin Reductase Pathway (Metabolic Pathway)

(MHR keeps Fe in Hgb reduced to the 2+ state)

Main enzyme is Methemoglobin reductase

Hgb with Fe³+ is methemoglobin

Without methemoglobin reductase we get methemoglobinemia, resulting in cyanosis .

Methemoglobin can’t carry 0²

Hereditary enzyme deficiency, toxic substances that oxidize hgb, Hgb M disease

State the primary function of hemoglobin

(gas transport)

To transport oxygen from the lungs to the tissues and CO² from the tissues to the lungs for exhalation

What are the 2 major components of a normal Hgb molecule?

(Heme & Globin)

Describe the function and composition of heme

Ring of C, H, & N atoms called propophyrin IX (pyrole ring) with an atom of ferrous (Fe_²+) iron inserted

There 4 Hemes in each hgb

Describe Globin

(Amino acid chains of Hgb)

Teach hemoglobin molec has two pairs of poly. p. chains

141-146 aa per chain

Ferritin

(Iron +apoferritin)

Major storage form of Fe

Heme Iron

Iron in the “ferrous” or +2 form

Transferrin

(Plasma transport protein)

Fe₃+ iron bound to plasma transport protein

Carries Iron in the Ferric state

Hemosiderin

(Intracellular storage form of Fe)

Breakdown product of ferritin

Found in the kidneys

also acts to store Fe

List the Intrauterine Hemoglobins

(Gower 1, Gower 2, Portland)

1) Gower 1 (ζ₂ε₂) zeta₂ epsilon₂

₂₎ Gower 2 (a₂ε₂) alpha₂ epsilon₂

₃₎ Portland (ζ₂γ₂) zeta₂ gamma ₂

List the Hemoglobin found at birth

(HgB F & Hgb A)

1) Hgb F (α₂γ₂)   alpha₂ gamma₂   (60-90%)

2) Hgb A (α₂β₂)   alpha₂ beta_{2 -} the rest is filled by the deficit left by Hgb F

Normal Adult Hemoglobin Chains

List ~% & Composition of each chain

(Hgb A, Hgb A₂, Hga F

1) Hgb A (α₂β₂)    alpha₂ beta₂ (> 95%)

2) Hgb A₂ (a₂δ₂ )  alpha₂ delta₂ (~ 2%)

3) Hgb F (a₂γ₂ )   alpha₂ gamma₂ (1-2%)

Normal intrauterine Hemoglobin Chains

List ~% & Composition of each chain

Gower 1 (zeta2 epsilon2)

Gower 2 (alpha2 episilon 2)

Portland (zeta2 gamma 2)

Hemoglobin-Oxygen Dissociation curve

(Describes respiratory movement, oxygen loading/unloading)

Normal curve

2,3-BPG

(Control Hgb affinity for oxygen)

2,3-biphosphoglycerate

Increases the affinity for oxygen

P-50

The partial pressure at which hgb is 50% saturated under standard in vitro conditions

Reference Range:

P50 = 26-30 mmHg

As the P50 goes up, oxygen affinity goes down and more oxygen is released to the tissues.

Shift to the left

(Increases Hgb affinity for O2, decreases O2 delivery to tissue)

Cause abnormal Hgbs with increase O2 affinities

undesirable

Decrease BPG

about 12% of oxygen is delivered to tissues

P50 goes down to ~ 23 mmHg

Shift to the right

(Decreases Hgb affinity for O2, increases O2 delivery to tissues)

Mediate by increased 2,3-BPG

In response to hypoxia

desireable

P50 increases to ~40 mmHg

50% opposed to 25% of oxygen delivered to tissues

RBCs have become more efficient

Methemoglobin

(Hgb w Fe in 3+ state)

Can’t carry oxygen

Results in Shift to the left

Causes:

1) presence of nitrites

2) Decreased methemoglobin reductase

3) inherited hgb M disease

Sulfhemoglobin

(sulfur is added to pyrole ring)

Conversion of Fe to the ferric +3 state

HOWEVER, normally only 1-2 hemes affected and actually REDUCES remaining Hgb for oxygen so more oxygen can be delivered to tissues

Results in SHIFT TO THE RIGHT

Carboxyhemoglobin

(Carbon monoxide binds to Heme iron)

Hgb loves CO 200x more than O2

CO Bonds more slowly, but more strongly than O2

Completely eliminates O2 transport

Cherry red blood

MASSIVE SHIFT TO THE LEFFT

Define: cyanosis

Bluish-purple discoloration of the skin or mucous membranes that occurs when there's a decrease in the amount of oxygen bound to hemoglobin in red blood cells.
Methemoglobinemia will lead to this

length of normal rbc survival in circulation

120 days

 3 physiologic functions of the rbc membrane

1) maintaining osmotic balance between plasma and cell
2) Maintain cell shape and deformability - flexibility of cell allows for them to squeeze through vasculature and reduce flow resistance
3) Transport cellular ions & gases selective permeability - K+/Na+ pumps, O2, CO2, H2O, anions

Permiability of
1)H2O
2)Anions
3)Cations (K+/Na+)

1) simple diffusion
2) Integral proteins (channels) facilitate diffusion
3) Cation pumps (Cation gradients across the membrane are actively maintained by pumps keeping intracellular sodium low and intracellular potassium high)

Form of iron that is incorporated into the heme molecule

ferrous (Fe2+)

Define: Transferrin

Plasma protein that carries iron in Ferric (Fe3+) form

Define: Ferritin

Apoferritin carrying iron. A major storage form of iron
Found in most tissues as a cytosolic protein - also in plasma

Define: Apoferritin

The protein shell of ferritin, meaning it is the iron-free form of the protein

Define: Hemosiderin

Intracellular storage form of iron; breakdown product of ferritin

Define: cyanosis

Bluish-purple discoloration of the skin or mucous membranes that occurs when there's a decrease in the amount of oxygen bound to hemoglobin in red blood cells.
Methemoglobinemia will lead to this