NEET MDS Lessons
Physiology
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.
|
Blood Group |
Antigens on RBCs |
Antibodies in Serum |
Genotypes |
|
A |
A |
Anti-B |
AA or AO |
|
B |
B |
Anti-A |
BB or BO |
|
AB |
A and B |
Neither |
AB |
|
O |
Neither |
Anti-A and anti-B |
OO |
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.
Red blood cell cycle:
RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.
Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.
Erythropoietin Mechanism:
Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.
It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.
Membrane Structure & Function
Cell Membranes
- Cell membranes are phospholipid bilayers (2 layers)
- Bilayer forms a barrier to passage of molecules in an out of cell
- Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
- Cholesterol (another lipid) stabilizes cell membranes
- the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water
Membranes Also Contain Proteins
- Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
- Hydrophobic = doesn't like water = likes lipids
- Membrane proteins have many functions:
- receptors for hormones
- pumps for transporting materials across the membrane
- ion channels
- adhesion molecules for holding cells to extracellular matrix
cell recognition antigens
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.
HEART DISORDERS
- Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
- Renin release (Juxtaglomerular cells) Kidney
- Converts Angiotensinogen => Angiotensin I
- In lungs Angiotensin I Converted => Angiotensin II
- Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
- stimulates thirst
- stimulates adrenal cortex to release Aldosterone
(Sodium retention, potassium loss) - stimulates kidney directly to reabsorb Sodium
- releases ADH from Posterior Pituitary
- Myocardial Infarction
- Myocardial Cells die from lack of Oxygen
- Adjacent vessels (collateral) dilate to compensate
- Intracellular Enzymes leak from dying cells (Necrosis)
- Creatine Kinase CK (Creatine Phosphokinase) 3 forms
- One isoenzyme = exclusively Heart (MB)
- CK-MB blood levels found 2-5 hrs, peak in 24 hrs
- Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
- Serum glutamic oxaloacetic transaminase (SGOT)
- Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
- SGOT returns to normal after 3-4 days
- Creatine Kinase CK (Creatine Phosphokinase) 3 forms
- Myocardium weakens = Decreased CO & SV (severe - death)
- Infarct heal by fibrous repair
- Hypertrophy of undamaged myocardial cells
- Increased contractility to restore normal CO
- Improved by exercise program
- Prognosis
- 10% uncomplicated recovery
- 20% Suddenly fatal
- Rest MI not fatal immediately, 15% will die from related causes
- Congenital heart disease (Affect oxygenation of blood)
- Septal defects
- Ductus arteriosus
- Valvular heart disease
- Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
- Regurgitation = cusps, retracted, Do not close, blood moves backwards
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+)
A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.
Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.
Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.
Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.
Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects
Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.
1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.
2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.
3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.
4) Ventricular repolarization occurs.