Serum Lipids

• Total cholesterol is the sum of
  • HDL cholesterol
  • LDL cholesterol and
  • 20% of the triglyceride value
• Note that
  • high LDL values are bad, but
  • high HDL values are good.
• Using the various values, one can calculate a
  cardiac risk ratio = total cholesterol divided by HDL cholesterol
• A cardiac risk ratio greater than 7 is considered a warning.

Serum Proteins

Proteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins.

After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:

Serum is blood plasma without fibrinogen and other clotting factors.

The serum proteins can be separated by electrophoresis.

• The most prominent of these and the one that moves closest to the positive electrode is serum albumin.
• Serum albumin
  • is made in the liver
  • binds many small molecules for transport through the blood
  • helps maintain the osmotic pressure of the blood
• The other proteins are the various serum globulins.
  • alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A])
  • beta globulins (e.g., the iron-transporting protein transferrin)
  • gamma globulins.
    • Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.)
    • Most antibodies are gamma globulins.
    • Therefore gamma globulins become more abundant following infections or immunizations. 

Respiration involves several components:

Ventilation - the exchange of respiratory gases (O₂ and CO₂) between the atmosphere and the lungs. This involves gas pressures and muscle contractions.

External respiration - the exchange of gases between the lungs and the blood. This involves partial pressures of gases, diffusion, and the chemical reactions involved in transport of O₂and CO₂.

Internal respiration - the exchange of gases between the blood and the systemic tissues. This involves the same processes as external respiration.

Cellular respiration - the includes the metabolic pathways which utilize oxygen and produce carbon dioxide, which will not be included in this unit.

Ventilation is composed of two parts: inspiration and expiration. Each of these can be described as being either quiet, the process at rest, or forced, the process when active such as when exercising.

Quiet inspiration:

The diaphragm contracts, this causes an increase in volume of the thorax and the lungs, which causes a decrease in pressure of the thorax and lungs, which causes air to enter the lungs, moving down its pressure gradient. Air moves into the lungs to fill the partial vacuum created by the increase in volume.

Forced inspiration:

Other muscles aid in the increase in thoracic and lung volumes.

The scalenes - pull up on the first and second ribs.

The sternocleidomastoid muscles pull up on the clavicle and sternum.

The pectoralis minor pulls forward on the ribs.

The external intercostals are especially important because they spread the ribs apart, thus increasing thoracic volume. It's these muscles whose contraction produces the "costal breathing" during rapid respirations.

Quiet expiration:

The diaphragm relaxes. The elasticity of the muscle tissue and of the lung stroma causes recoil which returns the lungs to their volume before inspiration. The reduced volume causes the pressure in the lungs to increase thus causing air to leave the lungs due to the pressure gradient.

Forced Expiration:

The following muscles aid in reducing the volume of the thorax and lungs:

The internal intercostals - these compress the ribs together

The abdominus rectus and abdominal obliques: internal obliques, external obliques- these muscles push the diaphragm up by compressing the abdomen.

Respiratory output is determined by the minute volume, calculated by multiplying the respiratory rate time the tidal volume.

Minute Volume = Rate (breaths per minute) X Tidal Volume (ml/breath)

Rate of respiration at rest varies from about 12 to 15 . Tidal volume averages 500 ml Assuming a rate of 12 breaths per minute and a tidal volume of 500, the restful minute volume is 6000 ml. Rates can, with strenuous exercise, increase to 30 to 40 and volumes can increase to around half the vital capacity.

Not all of this air ventilates the alveoli, even under maximal conditions. The conducting zone volume is about 150 ml and of each breath this amount does not extend into the respiratory zone. The Alveolar Ventilation Rate, AVR, is the volume per minute ventilating the alveoli and is calculated by multiplying the rate times the (tidal volume-less the conducting zone volume).

AVR = Rate X (Tidal Volume - 150 ml)

For a calculation using the same restful rate and volume as above this yields 4200 ml.

Since each breath sacrifices 150 ml to the conducting zone, more alveolar ventilation occurs when the volume is increased rather than the rate.

During inspiration the pressure inside the lungs (the intrapulmonary pressure) decreases to -1 to -3 mmHg compared to the atmosphere. The variation is related to the forcefulness and depth of inspiration. During expiration the intrapulmonary pressure increases to +1 to +3 mmHg compared to the atmosphere. The pressure oscillates around zero or atmospheric pressure.

The intrapleural pressure is always negative compared to the atmosphere. This is necessary in order to exert a pulling action on the lungs. The pressure varies from about -4 mmHg at the end of expiration, to -8 mmHg and the end of inspiration.

The tendency of the lungs to expand, called compliance or distensibility, is due to the pulling action exerted by the pleural membranes. Expansion is also facilitated by the action of surfactant in preventing the collapse of the alveoli.

The opposite tendency is called elasticity or recoil, and is the process by which the lungs return to their original or resting volume. Recoil is due to the elastic stroma of the lungs and the series elastic elements of the respiratory muscles, particularly the diaphragm.

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.  

The small intestine

Digestion within the small intestine produces a mixture of disaccharides, peptides, fatty acids, and monoglycerides. The final digestion and absorption of these substances occurs in the villi, which line the inner surface of the small intestine.

This scanning electron micrograph (courtesy of Keith R. Porter) shows the villi carpeting the inner surface of the small intestine.

The crypts at the base of the villi contain stem cells that continuously divide by mitosis producing

• more stem cells
• cells that migrate up the surface of the villus while differentiating into
  1. columnar epithelial cells (the majority). They are responsible for digestion and absorption.
  2. goblet cells, which secrete mucus;
  3. endocrine cells, which secrete a variety of hormones;
• Paneth cells, which secrete antimicrobial peptides that sterilize the contents of the intestine.

All of these cells replace older cells that continuously die by apoptosis.

The villi increase the surface area of the small intestine to many times what it would be if it were simply a tube with smooth walls. In addition, the apical (exposed) surface of the epithelial cells of each villus is covered with microvilli (also known as a "brush border"). Thanks largely to these, the total surface area of the intestine is almost 200 square meters, about the size of the singles area of a tennis court and some 100 times the surface area of the exterior of the body.

Incorporated in the plasma membrane of the microvilli are a number of enzymes that complete digestion:

• aminopeptidases attack the amino terminal (N-terminal) of peptides producing amino acids.
• disaccharidasesThese enzymes convert disaccharides into their monosaccharide subunits.
  • maltase hydrolyzes maltose into glucose.
  • sucrase hydrolyzes sucrose (common table sugar) into glucose and fructose.
  • lactase hydrolyzes lactose (milk sugar) into glucose and galactose.

Fructose simply diffuses into the villi, but both glucose and galactose are absorbed by active transport.

• fatty acids and monoglycerides. These become resynthesized into fats as they enter the cells of the villus. The resulting small droplets of fat are then discharged by exocytosis into the lymph vessels, called lacteals, draining the villi.

1.Rhythmicity ( Chronotropism ) :  means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization )  . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.

There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
-  transplanted heart continues to beat regularly without any nerve supply.
-  Embryologically the heart starts to beat before reaching any nerves to them.
-  Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.

Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.

Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system  is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.

These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.

The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) . 

The threshold is also less negative than that of nerve cells ( -40 millivolts ).

The decreased permeability to potassium from its side decrease the eflux  of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape

Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.

Factors , affecting the rhythmicity of the cardiac muscle :

I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia

II. Factors that decrease rhythmicity ( negative chronotropic):

1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.