Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO₂) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O₂  <= === => HbO₂ + H+

3.    binding gets more efficient as each O₂ binds
4.    release gets easier as each O₂ is released

5.    Several factors regulate AFFINITY of O₂

a.    Partial Pressure of O₂
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O₂

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O₂ unloaded

C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

Cystic Fibrosis
→ Thick mucus coagulates in ducts, produces obstruction, Too thick for cilia to move
 
→ Major Systems Affected: Respiratory System, G. I. Tract,Reproductive Tract

→ Inherited, autosomal recessive gene, most common fatal genetic disorder

→    Major characteristic, Altered electrolyte composition (Saliva & sweat Na+, K+, Cl-)

→    Family history of Cystic Fibrosis
→    Respiratory Infections & G.I.Tract malabsorption
→    Predisposes lung to Secondary infection (Staphylococcus, Pseudomonas)
→    Damages Respiratory Bronchioles and Alveolar ducts, Produces Fibrosis of Lungs, Large cystic dilations)

Serum Lipids

• Total cholesterol is the sum of
  • HDL cholesterol
  • LDL cholesterol and
  • 20% of the triglyceride value
• Note that
  • high LDL values are bad, but
  • high HDL values are good.
• Using the various values, one can calculate a
  cardiac risk ratio = total cholesterol divided by HDL cholesterol
• A cardiac risk ratio greater than 7 is considered a warning.

HEART DISORDERS

1. Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
   1. Renin release (Juxtaglomerular cells) Kidney
   2. Converts Angiotensinogen => Angiotensin I
   3. In lungs Angiotensin I Converted => Angiotensin II
   4. Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
      1. stimulates thirst
      2. stimulates adrenal cortex to release Aldosterone
         (Sodium retention, potassium loss)
      3. stimulates kidney directly to reabsorb Sodium
      4. releases ADH from Posterior Pituitary
2. Myocardial Infarction

    

   1. Myocardial Cells die from lack of Oxygen
   2. Adjacent vessels (collateral) dilate to compensate
   3. Intracellular Enzymes leak from dying cells (Necrosis)
      1. Creatine Kinase CK (Creatine Phosphokinase) 3 forms
         1. One isoenzyme = exclusively Heart (MB)
         2. CK-MB blood levels found 2-5 hrs, peak in 24 hrs
         3. Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
      2. Serum glutamic oxaloacetic transaminase (SGOT)
         1. Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
         2. SGOT returns to normal after 3-4 days
   4. Myocardium weakens = Decreased CO & SV (severe - death)
   5. Infarct heal by fibrous repair
   6. Hypertrophy of undamaged myocardial cells
      1. Increased contractility to restore normal CO
      2. Improved by exercise program
   7. Prognosis
      1. 10% uncomplicated recovery
      2. 20% Suddenly fatal
      3. Rest MI not fatal immediately, 15% will die from related causes
3. Congenital heart disease (Affect oxygenation of blood)
   1. Septal defects
   2. Ductus arteriosus
   3. Valvular heart disease
      1. Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
      2. Regurgitation = cusps, retracted, Do not close, blood moves backwards

Oxygen Uptake in the Lungs is Increased About 70X by Hemoglobin in the Red Cells

• In the lungs oxygen must enter the blood
• A small amount of oxygen dissolves directly in the serum, but 98.5% of the oxygen is carried by hemoglobin
• All of the hemoglobin is found within the red blood cells (RBCs or erythrocytes)
• The hemoglobin content of the blood is about 15 gm/deciliter (deciliter = 100 mL)
• Red cell count is about 5 million per microliter

Each Hemoglobin Can Bind Four O₂ Molecules (100% Saturation)

• Hemoglobin is a protein molecule with 4 protein sub-units (2 alphas and 2 betas)
  • Each of the 4 sub-units contains a heme group which gives the protein a red color
  • Each heme has an iron atom in the center which can bind an oxygen molecule (O2)
  • The 4 hemes in a hemoglobin can carry a maximum of 4 oxygen molecules
• When hemoglobin is saturated with oxygen it has a bright red color; as it loses oxygen it becomes bluish (cyanosis)

The Normal Blood Hematocrit is Just Below 50%

• Blood consists of cells suspended in serum
• More than 99% of the cells in the blood are red blood cells designed to carry oxygen
  • 25% of all the cells in the body are RBCs
• The volume percentage of cells in the blood is called the hematocrit
• Normal hematocrits are about 40% for women and 45% for men

At Sea Level the Partial Pressure of O₂ is High Enough to Give Nearly 100% Saturation of Hemoglobin

• As the partial pressure of oxygen in the alveoli increases the hemoglobin in the red cells passing through the lungs rises until the hemoglobin is 100% saturated with oxygen
  • At 100% saturation each hemoglobin carries 4 O₂ molecules
  • This is equal to 1.33 mL O₂ per gram of hemoglobin
• A person with 15 gm Hb/deciliter can carry:
  • Max O₂ carriage = 1.33 mL O₂/gm X 15 gm/deciliter = 20 mL O₂/deciliter
• A plot of % saturation vs pO2 gives an S-shaped "hemoglobin dissociation curve"
• At 100% saturation each hemoglobin binds 4 oxygen molecules

At High Altitudes Hemoglobin Saturation May be Well Below 100%

• At the alveolar pO₂ of 105 mm Hg at sea level the hemoglobin will be about 97% saturated, but the saturation will fall at high altitudes
• At 12,000 feet altitude alveolar pO₂ will be about 60 mm Hg and the hemoglobin will be 90% saturated
• At 29,000 feet (Mt. Everest) alveolar pO₂ is about 24 mm Hg and the hemoglobin will be only 42% saturated
• At very high altitudes most climbers must breath pure oxygen from tanks
• During acclimatization to high altitude the hematocrit can rise to about 60%- this increases the amount of oxygen that can be carried
• Hematocrits above 60% are not useful because the blood viscosity will increase to the point where it impairs circulation

Ingestion: Food taken in the mouth is

• ground into finer particles by the teeth,
• moistened and lubricated by saliva (secreted by three pairs of salivary glands)
• small amounts of starch are digested by the amylase present in saliva
• the resulting bolus of food is swallowed into the esophagus and
• carried by peristalsis to the stomach.