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Physiology

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.

 Pain, Temperature, and Crude Touch and Pressure

General somatic nociceptors, thermoreceptors, and mechanoreceptors sensitive to crude touch and pressure from the face conduct signals to the brainstem over GSA fibers of cranial nerves V, VII, IX, and X.

The afferent fibers involved are processes of monopolar neurons with cell bodies in the semilunar, geniculate, petrosal, and nodose ganglia, respectively.

The central processes of these neurons enter the spinal tract of V, where they descend through the brainstem for a short distance before terminating in the spinal nucleus of V.

Second-order neurons then cross over the opposite side of the brainstem at various levels to enter the ventral trigeminothalamic tract, where they ascend to the VPM of the thalamus.

Finally, third-order neurons project to the "face" area of the cerebral cortex in areas 3, 1, and 2 .

Discriminating Touch and Pressure

Signals are conducted from general somatic mechanoreceptors over GSA fibers of the trigeminal nerve into the principal sensory nucleus of V, located in the middle pons.

Second-order neurons then conduct the signals to the opposite side of the brainstem, where they ascend in the medial lemniscus to the VPM of the thalamus.

 Thalamic neurons then project to the "face" region of areas 3, I, and 2 of the cerebral cortex.

 Kinesthesia and Subconscious Proprioception

Proprioceptive input from the face is primarily conducted over GSA fibers of the trigeminal nerve.

The peripheral endings of these neurons are the general somatic mechanoreceptors sensitive to both conscious (kinesthetic) and subconscious proprioceptive input.

Their central processes extend from the mesencephalic nucleus to the principal sensory nucleus of V in the pons

The subconscious component is conducted to the cerebellum, while the conscious component travels to the cerebral cortex.

Certain second-order neurons from the principal sensory nucleus relay proprioceptive information concerning subconscious evaluation and integration into the ipsilateral cerebellum.

Other second-order neurons project to the opposite side of the pons and ascend to the VPM of the thalamus as the dorsal trigeminothalamic tract.

Thalamic projections terminate in the face area of the cerebral cortex.

Cardiac Control: The Cardiac Center in the medulla.

Outputs:

The cardioacceleratory center sends impulses through the sympathetic nervous system in the cardiac nerves. These fibers innervate the SA node and AV node and the ventricular myocardium. Effects on the SA and AV nodes are an increase in depolarization rate by reducing the resting membrane polarization. Effect on the myocardium is to increase contractility thus increasing force and therefore volume of contraction. Sympathetic stimulation increases both rate and volume of the heart.

The cardioinhibitory center sends impulses through the parasympathetic division, the vagus nerve, to the SA and AV nodes, but only sparingly to the atrial myocardium, and not at all to ventricular myocardium. Its effect is to slow the rate of depolarization by increasing the resting potential, i.e. hyperpolarization.

The parasympathetic division controls the heart at rest, keeping its rhythm slow and regular. This is referred to as normal vagal tone. Parasympathetic effects are inhibited and the sympathetic division exerts its effects during stress, i.e. exercise, emotions, "fight or flight" response, and temperature.

Inputs to the Cardiac Center:

Baroreceptors in the aortic and carotid sinuses. The baroreceptor reflex is responsible for the moment to moment maintenance of normal blood pressure.

Higher brain (hypothalamus): stimulates the center in response to exercise, emotions, "fight or flight", temperature.

Intrinsic Controls of the Heart:

Right Heart Reflex - Pressoreceptors (stretch receptors) in the right atrium respond to stretch due to increased venous return. The reflex acts through a short neural circuit to stimulate the sympathetic nervous system resulting in increased rate and force of contraction. This regulates output to input

The Frank-Starling Law - (Starling's Law of the Heart) - Like skeletal muscle the myocardium has a length tension curve which results in an optimum level of stretch producing the maximum force of contraction. A healthy heart normally operates at a stretch less than this optimum level and when exercise causes increased venous return and increased stretch of the myocardium, the result is increased force of contraction to automatically pump the increased volume out of the heart. I.e. the heart automatically compensates its output to its input.

An important relationship in cardiac output is this one:

Blood Flow =  D Pressure / Resistance to Blood Flow      

The Parathyroid Glands

The parathyroid glands are 4 tiny structures embedded in the rear surface of the thyroid gland. They secrete parathyroid hormone (PTH) a polypeptide of 84 amino acids. PTH increases the concentration of Ca2+ in the blood in three ways. PTH promotes

  • release of Ca2+ from the huge reservoir in the bones. (99% of the calcium in the body is incorporated in our bones.)
  • reabsorption of Ca2+ from the fluid in the tubules in the kidneys
  • absorption of Ca2+ from the contents of the intestine (this action is mediated by calcitriol, the active form of vitamin D.)

PTH also regulates the level of phosphate in the blood. Secretion of PTH reduces the efficiency with which phosphate is reclaimed in the proximal tubules of the kidney causing a drop in the phosphate concentration of the blood.

Hyperparathyroidism

Elevate the level of PTH causing a rise in the level of blood Ca2+ .Calcium may be withdrawn from the bones that they become brittle and break.

 Patients with this disorder have high levels of Ca2+ in their blood and excrete small amounts of Ca2+ in their urine. This causes hyperparathyroidism.

Hypoparathyroidism

This disorder have low levels of Ca2+ in their blood and excrete large amounts of Ca2+ in their urine.

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).

Levels of Organization:

CHEMICAL LEVEL - includes all chemical substances necessary for life (see, for example, a small portion - a heme group - of a hemoglobin molecule); together form the next higher level

CELLULAR LEVEL - cells are the basic structural and functional units of the human body & there are many different types of cells (e.g., muscle, nerve, blood)

TISSUE LEVEL - a tissue is a group of cells that perform a specific function and the basic types of tissues in the human body include epithelial, muscle, nervous, and connective tissues

ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g., heart, liver, stomach)

SYSTEM LEVEL - an association of organs that have a common function; the major systems in the human body include digestive, nervous, endocrine, circulatory, respiratory, urinary, and reproductive.

There are two types of cells that make up all living things on earth: prokaryotic and eukaryotic. Prokaryotic cells, like bacteria, have no 'nucleus', while eukaryotic cells, like those of the human body, do.

Neurons :

Types of neurons based on structure:

a multipolar neuron because it has many poles or processes, the dendrites and the axon. Multipolar neurons are found as motor neurons and interneurons. There are also bipolar neurons with two processes, a dendrite and an axon, and unipolar neurons, which have only one process, classified as an axon.. Unipolar neurons are found as most of the body's sensory neurons. Their dendrites are the exposed branches connected to receptors, the axon carries the action potential in to the central nervous system.

 

Types of neurons based on function:

  • motor neurons - these carry a message to a muscle, gland, or other effector. They are said to be efferent, i.e. they carry the message away from the central nervous system.
  • sensory neurons - these carry a message in to the CNS. They are afferent, i.e. going toward the brain or spinal cord.
  • interneuron (ie. association neuron, connecting neuron) - these neurons connect one neuron with another. For example in many reflexes interneurons connect the sensory neurons with the motor neurons.

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