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.

Typical Concentration Gradients and Membrane Potentials in Excitable Cells

The Na Pump is Particularly Important in the Kidney and Brain

• All cells have Na pumps in their membranes, but some cells have more than others
• Over-all Na pump activity may account for a third of your resting energy expenditure!
• In the kidney the Na pump activity is very high because it is used to regulate body salt and water concentrations
  • Kidneys use enormous amounts of energy: 0.5% of body weight, but use 7% of the oxygen supply
• Pump activity is also high in the brain because Na and K gradients are essential for nerves
  • The brain is another high energy organ; it is 2% of body weight, but uses 18% of the oxygen supply

In the Resting State Potassium Controls the Membrane Potential of Most Cells

• Resting cells have more open K channels than other types
• More K+ passes through membrane than other ions- therefore K+ controls the potential
• Blood K+ must be closely controlled because small changes will produce large changes in the membrane potentials of cells
  • Raising K will make the membrane potential less negative (depolarization)
• High blood K+ can cause the heart to stop beating (it goes into permanent contraction)

During an Action Potential Na Channels Open, and Na Controls the Membrane Potential

• Whichever ion has the most open channels controls the membrane potential
• Excitable cells have Na channels that open when stimulated
• When large numbers of these channels open Na controls the membrane potential

The Body Regulates pH in Several Ways

• Buffers are weak acid mixtures (such as bicarbonate/CO₂) which minimize pH change
  • Buffer is always a mixture of 2 compounds
    • One compound takes up H ions if there are too many (H acceptor)
    • The second compound releases H ions if there are not enough (H donor)
  • The strength of a buffer is given by the buffer capacity
    • Buffer capacity is proportional to the buffer concentration and to a parameter known as the pK
  • Mouth bacteria produce acids which attack teeth, producing caries (cavities). People with low buffer capacities in their saliva have more caries than those with high buffer capacities.
• CO₂ gas (a potential acid) is eliminated by the lungs
• Other acids and bases are eliminated by the kidneys

1 - Passive processes - require no expenditure of energy by a cell:

• Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:
  • concentration gradient
  • cross-sectional area through which diffusion occurs
  • temperature
  • molecular weight of a substance
  • distance through which diffusion occurs
• Osmosis = diffusion of water across a semi permeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration

• Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of 'carriers' (membrane proteins). In the example below, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an 'opening' in the protein through which a substance (e.g., sodium ions) can pass.

2 - Active processes - require the expenditure of energy by cells:

• Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule
• Endo- & exocytosis - moving material into (endo-) or out of (exo-) cell in bulk form

Red blood cell cycle:

RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.

Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.

Erythropoietin Mechanism:

Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.

HEART DISORDERS

1. Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
   1. Renin release (Juxtaglomerular cells) Kidney
   2. Converts Angiotensinogen => Angiotensin I
   3. In lungs Angiotensin I Converted => Angiotensin II
   4. Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
      1. stimulates thirst
      2. stimulates adrenal cortex to release Aldosterone
         (Sodium retention, potassium loss)
      3. stimulates kidney directly to reabsorb Sodium
      4. releases ADH from Posterior Pituitary
2. Myocardial Infarction

    

   1. Myocardial Cells die from lack of Oxygen
   2. Adjacent vessels (collateral) dilate to compensate
   3. Intracellular Enzymes leak from dying cells (Necrosis)
      1. Creatine Kinase CK (Creatine Phosphokinase) 3 forms
         1. One isoenzyme = exclusively Heart (MB)
         2. CK-MB blood levels found 2-5 hrs, peak in 24 hrs
         3. Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
      2. Serum glutamic oxaloacetic transaminase (SGOT)
         1. Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
         2. SGOT returns to normal after 3-4 days
   4. Myocardium weakens = Decreased CO & SV (severe - death)
   5. Infarct heal by fibrous repair
   6. Hypertrophy of undamaged myocardial cells
      1. Increased contractility to restore normal CO
      2. Improved by exercise program
   7. Prognosis
      1. 10% uncomplicated recovery
      2. 20% Suddenly fatal
      3. Rest MI not fatal immediately, 15% will die from related causes
3. Congenital heart disease (Affect oxygenation of blood)
   1. Septal defects
   2. Ductus arteriosus
   3. Valvular heart disease
      1. Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
      2. Regurgitation = cusps, retracted, Do not close, blood moves backwards