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.

Typical Concentration Gradients and Membrane Potentials in Excitable Cells

The Na Pump is Particularly Important in the Kidney and Brain

• All cells have Na pumps in their membranes, but some cells have more than others
• Over-all Na pump activity may account for a third of your resting energy expenditure!
• In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
  • Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
• Pump activity is also high in the brain because Na and K gradients are essential for nerves
  • The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply

In the Resting State Potassium Controls the Membrane Potential of Most Cells

• Resting cells have more open K channels than other types
• More K+ passes through membrane than other ions- therefore K+ controls the potential
• Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
  • Raising K will make the membrane potential less negative (depolarization)
• High blood K+ can cause the heart to stop beating (it goes into permanent contraction)

During an Action Potential Na Channels Open, and Na Controls the Membrane Potential

• Whichever ion has the most open channels controls the membrane potential
• Excitable cells have Na channels that open when stimulated
• When large numbers of these channels open Na controls the membrane potential

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

Functions

Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts

Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K

Detoxification -alcohol , drugs and medicines , environmental toxins

Protein metabolism -

• transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
• deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.

Glycemic Regulation - the management of blood glucose.

• glycogenesis - the conversion of glucose into glycogen.
• glycogenolysis - the breakdown of glycogen into glucose.

gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein

Physiology - science that describes how organisms FUNCTION and survive in continually changing environments  

Conductivity :

 Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another)  by the excitatory -conductive system of the heart.
 
Excitatory conductive system of the heart involves:

1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through  the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.

2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the  fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.

There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s)  .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction  , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s

3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .

4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.

Factors , affecting conductivity ( dromotropism)  :

I. Positive dromotropic factors :

1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis

II. Negative dromotropic factors :

1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.