Principal heart sounds

1. S1: closure of AV valves;typically auscultated as a single sound 

Clinical note: In certain circumstances, S1 may be accentuated. This occurs when the valve leaflets are “slammed” shut in early systole from a greater than normal distance because they have not had time to drift closer together. Three conditions that can result in an accentuated S1 are a shortened PR interval, mild mitral stenosis, and high cardiac-output states or tachycardia.

2. S2: closure of semilunar valves in early diastole , normally “split” during inspiration . S2: best appreciated in the 2nd or 3rd left intercostal space

Clinical note: Paradoxical or “reversed” splitting occurs when S2 splitting occurs with expiration and disappears on inspiration. Moreover, in paradoxical splitting, the pulmonic valve closes before the aortic valve, such that P2 precedes A2. The most common cause is left bundle branch block (LBBB). In LBBB, depolarization of the left ventricle is impaired, resulting in delayed left ventricular contraction and aortic valve closure.

3. S3: ventricular gallop, presence reflects volume-overloaded state 
 
 Clinical note: An S3 is usually caused by volume overload in congestive heart failure. It can also be associated with valvular disease, such as advanced mitral regurgitation, in which the “regurgitated” blood increases the rate of ventricular filling during early diastole.
 
4. S4: atrial gallop, S4: atrial contraction against a stiff ventricle, often heard after an acute myocardial infarction.

Clinical note: An S4 usually indicates decreased ventricular compliance (i.e., the ventricle does not relax as easily), which is commonly associated with ventricular hypertrophy or myocardial ischemia. An S4 is almost always present after an acute myocardial infarction. It is loudest at the apex with the patient in the left lateral decubitus position (lying on their left side).

Carbon Dioxide Transport

Carbon dioxide (CO₂) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H⁺) and a bicarbonate ions:

CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻

95% of the CO₂ generated in the tissues is carried in the red blood cells:

• It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
• Once inside, about one-half of the CO₂ is directly bound to hemoglobin (at a site different from the one that binds oxygen).
• The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
  • bicarbonate ions that diffuse back out into the plasma and
  • hydrogen ions (H⁺) that bind to the protein portion of the hemoglobin (thus having no effect on pH).

Only about 5% of the CO₂ generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO₂ we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO₂ is released to the air of the alveoli.

Respiratory system plays important role in maintaining homeostasis . Other than its major function , which is supplying the cells with needed oxygen to produce energy and getting rid of carbon dioxide , it has other functions :

1 Vocalization , or sound production.
2 Participation in acid base balance .
3 Participation in fluid balance by insensible water elimination (vapors ).
4 Facilitating venous return .
5 Participation in blood pressure regulation : Lungs produce Angiotensin converting enzyme ( ACE ) .
6 Immune function : Lungs produce mucous that trap foreign particles , and have ciliae that move foreign particles away from the lung. They also produce alpha 1 antitrepsin that protect the lungs themselves from the effect of elastase and other proteolytic  enzymes

Hormones are carried by the blood throughout the entire body, yet they affect only certain cells.  The specific cells that respond to a given hormone have receptor sites for that hormone.  

This is sort of a lock and key mechanism.  If the key fits the lock, then the door will open.  If a hormone fits the receptor site, then there will be an effect.  If a hormone and a receptor site do not match, then there is no reaction.  All of the cells that have receptor sites for a given hormone make up the target tissue for that hormone.  In some cases, the target tissue is localized in a single gland or organ.  In other cases, the target tissue is diffuse and scattered throughout the body so that many areas are affected.  

Hormones bring about their characteristic effects on target cells by modifying cellular activity.  Cells in a target tissue have receptor sites for specific hormones.  Receptor sites may be located on the surface of the cell membrane or in the interior of the cell.

In general those protein hormones are unable to diffuse through the cell membrane and react with receptor sites on the surface of the cell.  The hormone receptor reaction on the cell membrane activates an enzyme within the membrane, called adenyl cyclase, which diffuses into the cytoplasm.  Within the cell, adenyl cyclase catalyzes or starts the process of removal of phosphates from ATP to produce cyclic adenosine monophosphate or c AMP.  This c AMP activates enzymes within the cytoplasm that alter or change the cellular activity.  The protein hormone, which reacts at the cell membrane, is called the first messenger.  c Amp that brings about the action attributed to the hormone is called the second messenger.  This type of action is relatively rapid because the precursors are already present and they just needed to be activated in some way.  

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.

The nephron of the kidney is involved in the regulation of water and soluble substances in blood.

A Nephron

A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.

 Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.

It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

The Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.

A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.

The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.

Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.

Proximal Convoluted Tubule

The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.

Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.

Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.

The Loop of Henle

The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.

Distal Convoluted Tubule and Collecting Duct

The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.

Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.

The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.