Hemostasis - the  stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:

1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.

2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.

3) Formation of the Blood Clot:

A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.

B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.

C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.

The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.

Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.

Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.

Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are  VIII, IX, and XI.

Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage

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.

Maintenance of Homeostasis

The kidneys maintain the homeostasis of several important internal conditions by controlling the excretion of substances out of the body. 

Ions. The kidney can control the excretion of potassium, sodium, calcium, magnesium, phosphate, and chloride ions into urine. In cases where these ions reach a higher than normal concentration, the kidneys can increase their excretion out of the body to return them to a normal level. Conversely, the kidneys can conserve these ions when they are present in lower than normal levels by allowing the ions to be reabsorbed into the blood during filtration. (See more about ions.)
 
pH. The kidneys monitor and regulate the levels of hydrogen ions (H+) and bicarbonate ions in the blood to control blood pH. H+ ions are produced as a natural byproduct of the metabolism of dietary proteins and accumulate in the blood over time. The kidneys excrete excess H+ ions into urine for elimination from the body. The kidneys also conserve bicarbonate ions, which act as important pH buffers in the blood.
 
Osmolarity. The cells of the body need to grow in an isotonic environment in order to maintain their fluid and electrolyte balance. The kidneys maintain the body’s osmotic balance by controlling the amount of water that is filtered out of the blood and excreted into urine. When a person consumes a large amount of water, the kidneys reduce their reabsorption of water to allow the excess water to be excreted in urine. This results in the production of dilute, watery urine. In the case of the body being dehydrated, the kidneys reabsorb as much water as possible back into the blood to produce highly concentrated urine full of excreted ions and wastes. The changes in excretion of water are controlled by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and released by the posterior pituitary gland to help the body retain water.
 
Blood Pressure. The kidneys monitor the body’s blood pressure to help maintain homeostasis. When blood pressure is elevated, the kidneys can help to reduce blood pressure by reducing the volume of blood in the body. The kidneys are able to reduce blood volume by reducing the reabsorption of water into the blood and producing watery, dilute urine. When blood pressure becomes too low, the kidneys can produce the enzyme renin to constrict blood vessels and produce concentrated urine, which allows more water to remain in the blood.

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

Structure of a nerve:

A peripheral nerve is arranged much like a muscle in terms of its connective tissue. It has an outer covering which forms a sheath around the nerve, called the epineurium. Often a nerve will run together with an artery and vein and their connective coverings will merge. Nerve fibers, which are axons, organize into bundles known as fascicles with each fascicle surrounded by the perineurium. Between individual nerve fibers is an inner layer of endoneurium.

 The myelin sheath in peripheral nerves consists of Schwann cells wrapped in many layers around the axon fibers. Not all fibers in a nerve will be myelinated, but most of the voluntary fibers are. The Schwann cells are portrayed as arranged along the axon like sausages on a string. Gaps between the Schwann cells are called nodes of Ranvier. These nodes permit an impulse to travel faster because it doesn't need to depolarize each area of a membrane, just the nodes. This type of conduction is called saltatory conduction and means that impulses will travel faster in myelinated fibers than in unmyelinated ones.

The myelin sheath does several things:

1) It provides insulation to help prevent short circuiting between fibers.

2) The myelin sheath provides for faster conduction.

3) The myelin sheath provides for the possibility of repair of peripheral nerve fibers. Schwann cells help to maintain the micro-environments of the axons and their tunnel (the neurilemma tunnel) permits re-connection with an effector or receptor  CNS fibers, not having the same type of myelination accumulate scar tissue after damage, which prevents regeneration.

The Cardiac Cycle: the sequence of events in one heartbeat.

systole - the contraction phase; unless otherwise specified refers to left ventricle, but each chamber has its own systole.

diastole - the relaxation phase; unless otherwise specified refers to left ventricle, but each chamber has its own diastole.

1) quiescent period - period when all chambers are at rest and filling. 70% of ventricular filling occurs during this period. The AV valves are open, the semilunar valves are closed.

2) atrial systole - pushes the last 30% of blood into the ventricle.

3) atrial diastole - atria begin filling.

4) ventricular systole - First the AV valves close causing the first heart sound, then after the isovolumetric contraction phase the semilunar valves open permitting ventricular ejection of blood into the arteries.

5) ventricular diastole - As the ventricles relax the semilunar valves close first producing the second heart sound, then after the isovolumetric relaxation phase the AV valves open allowing ventricular filling.