Blood Groups

Blood groups are created by molecules present on the surface of red blood cells (and often on other cells as well).

The ABO Blood Groups

The ABO blood groups are the most important in assuring safe blood transfusions.

When red blood cells carrying one or both antigens are exposed to the corresponding antibodies, they agglutinate; that is, clump together. People usually have antibodies against those red cell antigens that they lack.

The critical principle to be followed is that transfused blood must not contain red cells that the recipient's antibodies can clump. Although theoretically it is possible to transfuse group O blood into any recipient, the antibodies in the donated plasma can damage the recipient's red cells. Thus all transfusions should be done with exactly-matched blood.

The Rh System

Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. They are named for the rhesus monkey in which they were first discovered.

There are a number of Rh antigens. Red cells that are "Rh positive" express the one designated D. About 15% of the population have no RhD antigens and thus are "Rh negative".

The major importance of the Rh system for human health is to avoid the danger of RhD incompatibility between mother and fetus.

During birth, there is often a leakage of the baby's red blood cells into the mother's circulation. If the baby is Rh positive (having inherited the trait from its father) and the mother Rh-negative, these red cells will cause her to develop antibodies against the RhD antigen. The antibodies, usually of the IgG class, do not cause any problems for that child, but can cross the placenta and attack the red cells of a subsequent Rh⁺ fetus. This destroys the red cells producing anemia and jaundice. The disease, called erythroblastosis fetalis or hemolytic disease of the newborn, may be so severe as to kill the fetus or even the newborn infant. It is an example of an antibody-mediated cytotoxicity disorder.

Although certain other red cell antigens (in addition to Rh) sometimes cause problems for a fetus, an ABO incompatibility does not. Rh incompatibility so dangerous when ABO incompatibility is not

It turns out that most anti-A or anti-B antibodies are of the IgM class and these do not cross the placenta. In fact, an Rh⁻/type O mother carrying an Rh⁺/type A, B, or AB fetus is resistant to sensitization to the Rh antigen. Presumably her anti-A and anti-B antibodies destroy any fetal cells that enter her blood before they can elicit anti-Rh antibodies in her.

This phenomenon has led to an extremely effective preventive measure to avoid Rh sensitization. Shortly after each birth of an Rh⁺ baby, the mother is given an injection of anti-Rh antibodies. The preparation is called Rh immune globulin (RhIG) or Rhogam. These passively acquired antibodies destroy any fetal cells that got into her circulation before they can elicit an active immune response in her.

Rh immune globulin came into common use in the United States in 1968, and within a decade the incidence of Rh hemolytic disease became very low.

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.

Bronchitis = Irreversible Bronchioconstriction
 .    Causes - Infection, Air polution, cigarette smoke

a.    Primary Defect = Enlargement & Over Activity of Mucous Glands, Secretions very viscous
b.    Hypertrophy & hyperplasia, Narrows & Blocks bronchi, Lumen of airway, significantly narrow
c.    Impaired Clearance by mucocillary elevator
d.    Microorganism retension in lower airways,Prone to Infectious Bronchitis, Pneumonia
e.    Permanent Inflamatory Changes IN epithelium, Narrows walls, Symptoms, Excessive sputum, coughing
f.    CAN CAUSE EMPHYSEMA

The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO₂ + H₂O <==> H₂CO₃ <==> H⁺ + HCO₃-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H⁺, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO₃- binds to H⁺
high pH     →   H₂CO₃ releases H⁺
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H⁺)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H⁺)

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.