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.

Production of Hormones

The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.

Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
 
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
 
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.

Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.

Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

• consists of four polypeptides:
  • two alpha (α) chains of 141 amino acids and
  • two beta (β) chains of 146 amino acids
• Each of these is attached the prosthetic group heme.
• There is one atom of iron at the center of each heme.
• One molecule of oxygen can bind to each heme.

The reaction is reversible.

• Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated hemoglobin of the venous blood becomes the bright-red oxyhemoglobin of the arterial blood.
• Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin gives up its oxygen.

The Lymphatic System

Functions of the lymphatic system:

1) to maintain the pressure and volume of the extracellular fluid by returning excess water and dissolved substances from the interstitial fluid to the circulation.

2) lymph nodes and other lymphoid tissues are the site of clonal production of immunocompetent  lymphocytes and macrophages in the specific immune response.
 

Filtration forces water and dissolved substances from the capillaries into the interstitial fluid. Not all of this water is returned to the blood by osmosis, and excess fluid is picked up by lymph capillaries to become lymph. From lymph capillaries fluid flows into lymph veins (lymphatic vessels) which virtually parallel the circulatory veins and are structurally very similar to them, including the presence of semilunar valves.

The lymphatic veins flow into one of two lymph ducts. The right lymph duct drains the right arm, shoulder area, and the right side of the head and neck. The left lymph duct, or thoracic duct, drains everything else, including the legs, GI tract and other abdominal organs, thoracic organs, and the left side of the head and neck and left arm and shoulder.

These ducts then drain into the subclavian veins on each side where they join the internal jugular veins to form the brachiocephalic veins.

Lymph nodes lie along the lymph veins successively filtering lymph. Afferent lymph veins enter each node, efferent veins lead to the next node becoming afferent veins upon reaching it.

Lymphokinetic motion (flow of the lymph) due to:

1) Lymph flows down the pressure gradient.

2) Muscular and respiratory pumps push lymph forward due to function of the semilunar valves.

Other lymphoid tissue: 

        1. Lymph nodes: Lymph nodes are small encapsulated organs located along the pathway of lymphatic vessels. They vary from about 1 mm to 1 to 2 cm in diameter and are widely distributed throughout the body, with large concentrations occurring in the areas of convergence of lymph vessels. They serve as filters through which lymph percolates on its way to the blood. Antigen-activated lymphocytes differentiate and proliferate by cloning in the lymph nodes. 

        2. Diffuse Lymphatic Tissue and Lymphatic nodules: The alimentary canal, respiratory passages, and genitourinary tract are guarded by accumulations of lymphatic tissue that are not enclosed by a capsule (i.e. they are diffuse) and are found in  connective tissue beneath the epithelial mucosa. These cells intercept foreign antigens and then travel to lymph nodes to undergo differentiation and proliferation. Local concentrations of lymphocytes in these systems and other areas are called lymphatic nodules. In general these are single and random but are more concentrated in the GI tract in the ileum, appendix, cecum, and tonsils. These are collectively called the Gut Associated Lymphatic Tissue (GALT). MALT (Mucosa Associated Lymphatic Tissue) includes these plus the diffuse lymph tissue in the respiratory tract. 

        3. The thymus:   The thymus is where immature lymphocytes differentiate into T-lymphocytes. The thymus is fully formed and functional at birth. Characteristic features of thymic structure persist until about puberty, when lymphocyte processing and proliferation are dramatically reduced and eventually eliminated and the thymic tissue is largely replaced by adipose tissue. The lymphocytes released by the thymus are carried to lymph nodes, spleen, and other lymphatic tissue where they form colonies. These colonies form the basis of T-lymphocyte proliferation in the specific immune response. T-lymphocytes survive for long periods and recirculate through lymphatic tissues.

        The transformation of primitive or immature lymphocytes into T-lymphocytes and their proliferation in the lymph nodes is promoted by a thymic hormone called thymosin.  Ocassionally the thymus persists and may become cancerous after puberty and and the continued secretion of thymosin and the production of abnormal T-cells may contribute to some autoimmune disorders.  Conversely, lack of thymosin may also allow inadequate immunologic surveillance and thymosin has been used experimentally to stimulate T-lymphocyte proliferation to fight lymphoma and other cancers. 

        4. The spleen: The spleen filters the blood and reacts immunologically to blood-borne antigens. This is both a morphologic (physical) and physiologic process. In addition to large numbers of lymphocytes the spleen contains specialized vascular spaces, a meshwork of reticular cells and fibers, and a rich supply of macrophages which monitor the blood.  Connective tissue forms a capsule and trabeculae which contain myofibroblasts, which are contractile.  The human spleen holds relatively little blood compared to other mammals, but it has the capacity for contraction to release this blood into the circulation during anoxic stress. White pulp in the spleen contains lymphocytes and is equivalent to other lymph tissue,  while red pulp contains large numbers of red blood cells that it filters and degrades.

    The spleen functions in both immune and hematopoietic systems. Immune functions include: proliferation of lymphocytes, production of antibodies, removal of antigens from the blood. Hematopoietic functions include: formation of blood cells during fetal life, removal and destruction of aged, damaged and abnormal red cells and platelets, retrieval of iron from hemoglobin degradation, storage of red blood cells.

(RDS) Respiratory distress of Newborn
1.    hyaline membrane disease of the new born
2.    decrease in surfactant, Weak, Abnormal complience of chest wall
3.    Small alveoli, difficult to inflate, Alveoli tent to collapse, many of varied sizes
4.    decrease in O2 diffusion area, lung difficult to expand, in compliance

Normal Chemical Composition of Urine

Urine is an aqueous solution of greater than 95% water, with a minimum of these remaining constituents, in order of decreasing concentration:

Urea 9.3 g/L.

Chloride 1.87 g/L.

Sodium 1.17 g/L.

Potassium 0.750 g/L.

Creatinine 0.670 g/L .

Other dissolved ions, inorganic and organic compounds (proteins, hormones, metabolites).

Urine is sterile until it reaches the urethra, where epithelial cells lining the urethra are colonized by facultatively anaerobic gram-negative rods and cocci. Urea is essentially a processed form of ammonia that is non-toxic to mammals, unlike ammonia, which can be highly toxic. It is processed from ammonia and carbon dioxide in the liver.