Red Blood Cells (erythrocytes)

• Women average about 4.8 million of these cells per cubic millimeter (mm³; which is the same as a microliter [µl]) of blood.
• Men average about 5.4 x 10⁶ per µl.
• These values can vary over quite a range depending on such factors as health and altitude.
• RBC precursors mature in the bone marrow closely attached to a macrophage.
• They manufacture hemoglobin until it accounts for some 90% of the dry weight of the cell.

• The nucleus is squeezed out of the cell and is ingested by the macrophage.

RBC have characteristic biconcave shape

Thus RBCs are terminally differentiated; that is, they can never divide. They live about 120 days and then are ingested by phagocytic cells in the liver and spleen. Most of the iron in their hemoglobin is reclaimed for reuse. The remainder of the heme portion of the molecule is degraded into bile pigments and excreted by the liver. Some 3 million RBCs die and are scavenged by the liver each second.

Red blood cells are responsible for the transport of oxygen and carbon dioxide.

Proteins:

• about 50 - 60% of the dry mass of a typical cell
• subunit is the amino acid & amino acids are linked by peptide bonds
• 2 functional categories = structural (proteins part of the structure of a cell like those in the cell membrane) & enzymes

Enzymes are catalysts. Enzymes bind temporarily to one or more of the reactants of the reaction they catalyze. In doing so, they lower the amount of activation energy needed and thus speed up the reaction

• Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions):

• Alveoli
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Alveolar capillaries
  • Entering the alveolar capillaries
    • PO₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
    • PCO₂ = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 

• While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

• Leaving the alveolar capillaries
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
• • Entering the systemic capillaries
    • PO₂ = 100 mm Hg
    • PCO₂ = 40 mm Hg
  • Body cells (resting conditions)
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
• • Leaving the systemic capillaries
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Exchange of gases takes place in Lungs

• A person with an average ventilation rate of 7.5 L/min will breathe in and out 10,800 liters of gas each day
• From this gas the person will take in about 420 liters of oxygen (19 moles/day) and will give out about 340 liters of carbon dioxide (15 moles/day)
• The ratio of CO₂ expired/O₂ inspired is called the respiratory quotient (RQ)
  • RQ = CO₂ out/O₂ in = 340/420 = 0.81
  • In cellular respiration of glucose CO₂ out = O₂ in; RQ = 1
  • The overall RQ is less than 1 because our diet is a mixture of carbohydrates and fat; the RQ for metabolizing fat is only 0.7
• All of the exchange of gas takes place in the lungs
• The lungs also give off large amounts of heat and water vapor

Principal heart sounds

1. S1: closure of AV valves;typically auscultated as a single sound 

Clinical note: In certain circumstances, S1 may be accentuated. This occurs when the valve leaflets are “slammed” shut in early systole from a greater than normal distance because they have not had time to drift closer together. Three conditions that can result in an accentuated S1 are a shortened PR interval, mild mitral stenosis, and high cardiac-output states or tachycardia.

2. S2: closure of semilunar valves in early diastole , normally “split” during inspiration . S2: best appreciated in the 2nd or 3rd left intercostal space

Clinical note: Paradoxical or “reversed” splitting occurs when S2 splitting occurs with expiration and disappears on inspiration. Moreover, in paradoxical splitting, the pulmonic valve closes before the aortic valve, such that P2 precedes A2. The most common cause is left bundle branch block (LBBB). In LBBB, depolarization of the left ventricle is impaired, resulting in delayed left ventricular contraction and aortic valve closure.

3. S3: ventricular gallop, presence reflects volume-overloaded state 
 
 Clinical note: An S3 is usually caused by volume overload in congestive heart failure. It can also be associated with valvular disease, such as advanced mitral regurgitation, in which the “regurgitated” blood increases the rate of ventricular filling during early diastole.
 
4. S4: atrial gallop, S4: atrial contraction against a stiff ventricle, often heard after an acute myocardial infarction.

Clinical note: An S4 usually indicates decreased ventricular compliance (i.e., the ventricle does not relax as easily), which is commonly associated with ventricular hypertrophy or myocardial ischemia. An S4 is almost always present after an acute myocardial infarction. It is loudest at the apex with the patient in the left lateral decubitus position (lying on their left side).

Carbon Dioxide Transport

Carbon dioxide (CO₂) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H⁺) and a bicarbonate ions:

CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻

95% of the CO₂ generated in the tissues is carried in the red blood cells:

• It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
• Once inside, about one-half of the CO₂ is directly bound to hemoglobin (at a site different from the one that binds oxygen).
• The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
  • bicarbonate ions that diffuse back out into the plasma and
  • hydrogen ions (H⁺) that bind to the protein portion of the hemoglobin (thus having no effect on pH).

Only about 5% of the CO₂ generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO₂ we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO₂ is released to the air of the alveoli.