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Physiology

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation. 

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting  contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.

A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:

  • relaxing arterioles
  • inhibiting the secretion of renin and aldosterone
  • inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.

The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.

The Heartbeat

During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.

The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.

The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.

When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.

The contraction of the heart in response to this electrical activity creates systole.

A period of recovery follows called diastole.

  • The heart muscle and S-A node become recharged.
  • The heart muscle relaxes.
  • The atria refill. 

The Electrocardiogram

The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG

Control of the Heart

Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.

  • One sends nerve impulses down accelerator nerves.
  • The other sends nerve impulses down a pair of vagus nerves

Accelerator Nerves

The accelerator nerves are part of the sympathetic branch of the autonomic nervous system, and  like all post-ganglionic sympathetic neurons  release noradrenaline at their endings on the heart.

They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.


Vigorous exercise accelerates heartbeat in two ways;

  • As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay  by the accelerator nerves  to the heart.
  • As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.

Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure

The Vagus Nerves

The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.

Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these  by way of the vagus nerves  to the heart. Heartbeat and blood pressure diminish.

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

As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment  of the small intestine. The duodenum is the first 10" of the small intestine

Two ducts enter the duodenum:

  • one draining the gall bladder and hence the liver
  • the other draining the exocrine portion of the pancreas.

From the intestinal mucosal cells, and from the liver and gallbladder. Secretions from the pancreas and bile from the gallbladder enter the duodenum through the hepatopancreatic ampulla and the sphincter of Oddi. These lie where the pancreatic duct and common bile duct join before entering the duodenum. The presence of fatty chyme in the duodenum causes release of the hormone CCK into the bloodstream. CCK is one of the enterogastrones and its main function, besides inhibiting the stomach, is to stimulate the release of enzymes by the pancreas, and the contraction of the gallbladder to release bile. It also stimulates the liver to produce bile. Consumption of excess fat results in excessive bile production by the liver, and this can lead to the formation of gallstones from precipitation of the bile salts. 

The acid in the chyme stimulates the release of secretin which causes the pancreas to release bicarbonate which neutralizes the acidity

Damage to Spinal Nerves and Spinal Cord

Damage

Possible cause of damage

Symptoms associated with innervated area

Peripheral nerve

Mechanical injury

Loss of muscle tone. Loss of reflexes. Flaccid paralysis. Denervation atrophy. Loss of sensation

Posterior root

Tabes dorsalis

Paresthesia. Intermittent sharp pains. Decreased sensitivity to pain. Loss of reflexes. Loss of sensation. Positive Romberg sign. High stepping and slapping of feet.

Anterior Horn

Poliomyelitis

Loss of muscle tone.  Loss of reflexes. Flaccid paralysis.  Denervation atrophy

Lamina X (gray matter)

Syringomyelia

Bilateral loss of pain and temperature sense only at afflicted cord level. Sensory dissociation. No sensory impairment below afflicted level

Anterior horn and lateral corticospinal tract

Amyotrophic lateral sclerosis

Muscle weakness.  Muscle atrophy. Fasciculations of hand and arm muscles. Spastic paralysis

Posterior and lateral funiculi

Subacute combined degeneration

Loss of position sense. Loss of vibratory sense. Positive Romberg sign. Muscle weakness. Spasticity. Hyperactive tendon reflexes. Positive Babinski sign.

Hemisection of the spinal cord

Mechanical injury

Brown-Sequard syndrome

Below cord level on injured side

Flaccid paralysis. Hyperactive tendon reflexes. Loss of position sense. Loss of vibratory sense. Tactile impairment

Below cord level on opposite side beginning one or two segments below injury

Loss of pain and temperature

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).

DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)

Transcription - DNA is used to produce mRNA

Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein . requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome


tRNA molecule

  • sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are 'read' by anticodons of tRNAs & tRNAs then 'deliver' their amino acid.
  • Amino acids are linked together by peptide bonds (see diagram to the right)
  • As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
  • The polypeptide chain then 'folds' in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.

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