GENERAL VISCERAL AFFERENT (GVA) PATHWAYS

Pain and Pressure Sensation via the Spinal Cord

Visceral pain receptors are located in peritoneal surfaces, pleural membranes, the dura mater, walls of arteries, and the walls of the GI tube.

Nociceptors in the walls of the GI tube are particularly sensitive to stretch and overdistension.

General visceral nociceptors conduct signals into the spinal cord over the monopolar neurons of the posterior root ganglia. They terminate in laminae III and IV of the posterior horn as do the pain and temperature pathways of the GSA system , their peripheral processes reach the visceral receptors via the gray rami communicantes and ganglia of the sympathetic chain

Second-order neurons from the posterior horn cross in the anterior white commissure and ascend to the thalamus in the anterior and lateral spinothalamic tracts,

Projections from the VPL of the thalamus relay signals to the sensory cortex.

The localization of visceral pain is relatively poor, making it difficult to tell the exact source of the stimuli.

Blood Pressure, Blood Chemistry, and Alveolar Stretch Detection

The walls of the aorta and the carotid sinuses contain special baroreceptors (pressure receptors) which respond to changes in blood pressure. These mechanoreceptors are the peripheral endings of GVA fibers of the glossopharyngeal (IX) and vagus (X) nerves

The GVA fibers from the carotid sinus baroreceptors enter the solitary tract of the brainstem and terminate in the vasomotor center of the medulla (Fig-14). This is the CNS control center for cardiovascular activity.

Stretch receptors in the alveoli of the lungs conduct information concerning rhythmic alveolar inflation and deflation over GVA X fibers to the solitary tract and then to the respiratory center of the brainstem. This route is an important link in the Hering-Breuer reflex, which helps to regulate respiration.

Carotid body chemoreceptors, sensitive to changes in blood PO2 and, to a lesser extent, PCO2 and pH, conduct signals to both the vasomotor and respiratory centers over GVA IX nerve fibers

GVA X fibers conduct similar information from the aortic chemoreceptors to both centers

Cystic Fibrosis
→ Thick mucus coagulates in ducts, produces obstruction, Too thick for cilia to move
 
→ Major Systems Affected: Respiratory System, G. I. Tract,Reproductive Tract

→ Inherited, autosomal recessive gene, most common fatal genetic disorder

→    Major characteristic, Altered electrolyte composition (Saliva & sweat Na+, K+, Cl-)

→    Family history of Cystic Fibrosis
→    Respiratory Infections & G.I.Tract malabsorption
→    Predisposes lung to Secondary infection (Staphylococcus, Pseudomonas)
→    Damages Respiratory Bronchioles and Alveolar ducts, Produces Fibrosis of Lungs, Large cystic dilations)

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.

A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.

Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.

Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.

Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.

Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects 

Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.

1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.

2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.

3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.

4) Ventricular repolarization occurs.

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.

Hyperventilation

1. Treatments :Rebreath air, hold breath (Increase CO₂)
   Give oxygen for Hypoxemia