Exchange of gases:

• External respiration:
  • exchange of O2 & CO2 between external environment & the cells of the body
  • efficient because alveoli and capillaries have very thin walls & are very abundant (your lungs have about 300 million alveoli with a total surface area of about 75 square meters)

• Internal respiration - intracellular use of O2 to make ATP
• occurs by simple diffusion along partial pressure gradients

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.

Cardiac Output:

Minute Volume = Heart Rate X Stroke Volume

Heart rate, HR at rest = 65 to 85 bpm  

Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.

Stroke volume, SV at rest = 60 to 70 ml.

Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.

Terms:

End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.

End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.

EDV - ESV = SV

SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.

Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood. 

Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.

Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.

Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.

Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart. 

The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases

Ventilation simply means inhaling and exhaling of air from the atmospheric air into lungs and then exhaling it from the lung into the atmospheric air.
Air pressure gradient has to exist between two atmospheres to enable a gas to move from one atmosphere to an other.
 

During inspiration: the intrathoracic pressure has to be less than that of atmospheric pressure. This could be achieved by decreasing the intrathoracic pressure as follows:
 

Depending on Boyle`s law , the pressure of gas is inversely proportional to the volume of its container. So increasing the intrathoracic volume will decrease the intrathoracic pressure which will allow the atmospheric air to be inhaled (inspiration) . As decreasing the intrathoracic volume will increase the intrathoracic pressure and causes exhaling of air ( expiration)

So. Inspiration  could be actively achieved by the contraction of inspiratory muscles : diaphragm and intercostal muscles. While relaxation of the mentioned muscles will passively cause expiration.
 

Contraction of diaphragm will pull the diaphragm down the abdominal cavity ( will move inferiorly)  , and then increase the intrathoracic volume ( vertically)  . Contraction of external intercostal muscle will pull the ribs upward and forward which will additionally increase the intrathoracic volume ( transversely  , the net result will be increasing the intrathoracic volume and decreasing the intrathoracic pressure.
 

Relaxation of diaphragm will move it superiorly during expiration, the relaxation of external intercostal muscles will pull the ribs downward and backward , and the elastic lungs and chest wall will recoil. The net result is decreasing the intrathoracic volume and increasing intrathoracic pressure.
 

All of this occurs during quiet breathing. During forceful inspiration an accessory inspiratory muscle will be involved ( scaleni , sternocleidomastoid , and others) to increase negativity in the intrathoracic pressure more and more.
 

During forceful expiration the accessory expiratory muscles ( internal intercostal muscles and abdominal muscles ) will be involved to decrease the intrathoracic volume  more and more and then to increase  intrathoracic pressure more and more.

The pressure within the alveoli is called intralveolar  pressure . Between the two phases of respiration it is equal to the atmospheric pressure. It is decreased during inspiration ( about 1 cm H₂O ) and increased during expiration ( about +1 cm H₂O ) . This difference allow entering of 0.5 L of air into the lungs.

Intrapleural pressure is the pressure of thin fluid between the two pleural layers . It is a slight negative pressure. At the beginning of inspiration it is about -5 cm H2O and reachs -7.5 cm H₂O at the end or inspiration.

At the beginning of expiration the intrapleural pressure is -7.5 cm H₂O and reaches -5 cmH₂O at the end of expiration.
The difference between intralveolar pressure and intrapleural pressure is called transpulmonary pressure.

Factors , affecting ventilation :
 

Resistance : Gradual decreasing of the diameter of respiratory airway increase the resistance to air flow.
 

Compliance : means the ease , which the lungs expand.It depends on both the elastic forces of the lungs and the elastic forces , caused by the the surface tension of the fluid, lining the alveoli.
 

Surface tension: Molecules of water have tendency to attract each other on the surface of water adjacent to air. In alveoli the surface tension caused by the fluid in the inner surface of the alveoli  may cause collapse of alveoli . The surface tension is decreased by the surfactant .

Surfactant is a mixture of phospholipids , proteins and ion m produced by type II pneumocytes.

Immature newborns may suffer from respiratory distress syndrome , due to lack of surfactant which is produced during the last trimester of pregnancy.
 

The elastic fibers of the thoracic wall also participate in lung compliance.

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.
 

Concentration versus diluting urine 

Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.                   
                                                   
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.

In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.

If plasma is hypotonic ADH will be inhibited and the diluted urine in distal  tubules will be excreted as diluted urine.

Urea  contributes to concentrating and diluting of urine as follows:

Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.