AdenosineTriphosphate (ATP)

• Animal cells cannot directly use most forms of energy
  • Most cellular processes require energy stored in the bonds of a molecule, adenosine triphosphate (ATP)
  • ATP is referred to as the energy currency of the cell

It is a nucleotide, formed from:

• the base adenine (the structure with 2 rings),
• the 5 carbon sugar deoxyribose (one ring)
• 3 phosphates

Energy is stored in the bonds between the phosphates and is released when the bonds are broken

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.

4.    Emphysema
1. Permanent enlargement of airways with distension of alveolar walls
 
    Thickened Bronchial Submucosa, Edema & Cellular Infiltration (loss of elasticity), Dilation of Air spaces, due to destruction of alveolar walls (Air trapped by obstruction)

2.    Lower Respiratory tree destruction

    Respiratory Bronchioles, Alveolar ducts, & Alveolar sacs

Types of Emphysema:
    
    1.    Centrilobular (Centriacinar) = Respiratory Bronchioles
    Rarely seen in non Smokers, More in Men than Women, Found in Smokers with Bronchitis

    2.    Panlobular (Panacinar) 

    Hereditary, Single autosomal recessive gene. Deficient in 1-globulin (1-antitrypsin), Protects respiratory tract from neutrophil elastase (Enzyme that distroys lung connective tissue) , Aged persons, Results from Bronchi or Bronchiolar constriction

    NOTE: Smoking = Leading cause of Bronchitis, Emphysema
 

Chemical Controls of Respiration

A.    Chemoreceptors (CO2, O2, H+)

1.    central chemoreceptors - located in the medulla
2.    peripheral chemoreceptors - large vessels of neck

B.    Carbon Dioxide Effects

1.    a powerful chemical regulator of breathing by increasing H+ (lowering pH)
    
a. hypercapnia            Carbon Dioxide increases -> 
                        Carbonic Acid increases ->
                        pH of CSF decreases (higher H+)- >
                        
DEPTH & RATE increase (hyperventilation)

b. hypocapnia - abnormally low Carbon Dioxide levels which can be produced by excessive hyperventilation; breathing into paper bag increases blood Carbon Dioxide levels

C.     Oxygen Effects

1.    aortic and carotid bodies - oxygen chemoreceptors

2.    slight Ox decrease - modulate Carb Diox receptors
3.    large Ox decrease - stimulate increase ventilation
4.    hypoxic drive - chronic elevation of Carb Diox (due to disease) causes Oxygen levels to have greater effect on regulation of breathing

D.    pH Effects (H+ ion)

1.    acidosis - acid buildup (H+) in blood, leads to increased RATE and DEPTH (lactic acid)

E.    Overview of Chemical Effects

 Chemical                             Breathing Effect

increased Carbon Dioxide (more H+)     increase
decreased Carbon Dioxide (less H+)     decrease

slight decrease in Oxygen             effect CO2 system
large decrease in Oxygen             increase ventilation

decreased pH (more H+)                 increase
increased pH (less H+)                 decrease

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.

Heart is a hollow muscular organ , that is located in the middle mediastinum  between the two bony structures of the sternum and the vertebral column ( a very important location for applying Cardiopulmonary Resuscitation - CPR- ) .
It has a shape of clenched fist , which weighs about 300 grams ( with mild variation between male and female ).
  Heart has an apex that is anteriorly , inferiorly , and leftward oriented , and a base , that is posteriorly , superiorly and rightward oriented   .
 In addition to its apex and base the heart has anterior , posterior and left surfaces.
 
 The wall of the heart is composed of three layers :
 
1. Endocardium : The innermost layer , which lines the heart chambers and is in direct contact with the blood . It is composed of endothelial cells that are similar to those , that line the blood vessels , and of connective tissue too. 
 Endocardium has a smooth surface that prevents blood clotting, as it ensures laminar blood flow .

 Clinical Physiology 
 Endocarditis is the inflammation of the endocardium , which is resistant to antibiotic treatment and difficult to cure.Endocarditis usually involves heart valves and chordae tendineae too.

 2. Myocardium  : The middle layer of the cardiac wall . It is the thickest among the three layers , and is composed of two types of cardiac muscles :
a. contractile muscle cells (form about 98-99% of the cardiac muscle ) .
 b- non-contractile muscle cells ( form about 1-2 % of the cardiac muscles and are the cells that form excitatory-conductive system of the heart).
 The cardiac muscle cells are similar to the skeletal muscles in that they are striated , but similar to the smooth muscles in being involuntary and connected to each others via gap junctions , that facilitate conduction of electrical potential from one cell to the others. Desmosomes adhere cardiac muscle cells to each others .

 3- Epicardium :  is the outermost and protective layer of the heart . It is composed of connective tissue , and form the inner layer of the pericardium ( visceral pericardium - see bellow).

 Pericardium: 
The heart is surrounded by a fluid-fill sac , which is known as pericardium . Pericardium is composed of two layers ( doubled layer membrane ) , between which a fluid-fill pericardial cavity exist .

 The outer layer is called fibrous pericardium , while the inner layer is called serous pericardium , which is subdivided into parietal pericardium and visceral pericardium . The visceral pericardium is the previously mentioned outermost layer of heart ( epicardium) .
Pericardial sac plays an important role in protection of heart from external hazards and infections , as it fixes the heart and limits its motion. It also prevents excessive dilation of the heart.

Clinical physiology: 

When there is excessive fluid in the pericardial cavity as a result of pericardial effusion , a cardiac tamponade will develop . cardiac tamponade means compression of the heart within the pericardial sac , which will prevent the relaxation of the heart ( heart will not be able to fully expand ) , and thus the circulating blood volume will be decreased (obstructive shock) . This is a life threatening situation which has to be urgently cured by  pericardiocentesis . 

Chambers of the heart : 

Heart has four chambers : two atria and two ventricles . The two right and left atria are separated from the two ventricles by the fibrous skeleton , which involves the right ( tricuspid ) and left ( bicuspid ) valves. Right and left atria are separated from each other by the interatrial  septum .
The two ventricles are separated by the interventricular septum.Interventricular septum is muscular in its lower thick part and fibrous in its upper thin part.
The two atria holds the blood returning from the veins and empty it only in a given right moment into the ventricles. Ventricles pump the blood into the arteries . 

Heart valves : 

There are four valves in the heart : Two atrioventricular valves and two semi-lunar valves:
1. Atrioventricular ( AV ) valves: These valves are found between the atria and ventricles , depending on the number of  the leaflets , the right atrioventricular valve is also called tricuspid valve (has three leaflets ) , while the left one is called bicuspid valve (has two leaflets ) . The shape of the bicuspid valve is similar to the mitre of bishop , so it is also called the mitral valve.
The leaflets of the valves are attached to fibrous threads (composed of collagen fibers ) , known as chordae tendineae , which from their side are attached to papillary muscles in the ventricles. These valves prevent backward flow of blood from ventricles during the systole. 

2. Semi-lunar valves : 

These valves are located on the base of the arteries ( aorta and pulmonary artery ) . They prevent the backward flow of blood from the arteries into ventricles.
The structure of the semilunar valves is quite different from that of the AV valves , as they have crescent-shaped cusps that do not have chorda tendinea , instead these cusps are like pockets which are filled of blood when it returns to the ventricles from the lumen of arteries during the diastole  , so they get closed and prevent the backward flow of blood.