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

Heart sounds

Heart sounds are a result of beating heart and resultant blood flow . that could be detected by a stethoscope during auscultation . Auscultation is a part of physical examination that doctors have to practice them perfectly.
Before discussion the origin and nature of the heart sounds we have to distinguish between the heart sounds and hurt murmurs. Heart murmurs are pathological noises that results from abnormal blood flow in the heart or blood vessels.
Physiologically , blood flow has a laminar pattern , which means that blood flows in form of layers , where the central layer is the most rapid . Laminar blood flow could be turned into turbulent one .

Turbulent blood flow is a result of stenotic ( narrowed ) valves or blood vessels , insufficient valves , roughened vessels` wall or endocardium ,  and many diseases . The turbulent blood flow causes noisy murmurs inside or outside the heart.

Heart sounds ( especially first and second sounds ) are mainly a result of closure of the valves of the heart . While the third sound is a result of vibration of ventricular wall and the leaflets of the opened AV valves after rapid inflow of blood from the atria to ventricles . 

Third heart sound is physiologic in children but pathological in adults.

The four heart sound is a result of the atrial systole and vibration of the AV valves , due to blood rush during atrial systole . It is inaudible neither in adults nor in children . It is just detectable by the phonocardiogram .

Characteristic of heart sounds :

1. First heart sound  (S1 , lub ) : a soft and low pitch sound, caused by closure of AV valves.Usually has two components ( M1( mitral ) and T1 ( tricuspid ). Normally M1 preceads T1.

2. Second heart sound ( S2 , dub) : sharp and high pitch sound . caused by closure of semilunar valves. It also has two components A2 ( aortic) and P2 ( pulmonary) . A2 preceads P2.

3. Third heart sound (S3) : low pitched sound.

4. Fourth heart sound ( S4) very low pitched sound.

As we notice : the first three sounds are related to ventricular activity , while the fourth heart sound is related to atrial activity.
Closure of valves is not the direct cause for heart sounds , but sharp blocking of blood of backward returning of blood by the closing valve is the direct cause.
 

Exchange of gases:

• External respiration:
  • exchange of O2 & CO2 between external environment & the cells of the body
  • efficient because alveoli and capillaries have very thin walls & are very abundant (your lungs have about 300 million alveoli with a total surface area of about 75 square meters)

• Internal respiration - intracellular use of O2 to make ATP
• occurs by simple diffusion along partial pressure gradients

Conductivity :

 Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another)  by the excitatory -conductive system of the heart.
 
Excitatory conductive system of the heart involves:

1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through  the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.

2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the  fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.

There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s)  .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction  , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s

3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .

4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.

Factors , affecting conductivity ( dromotropism)  :

I. Positive dromotropic factors :

1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis

II. Negative dromotropic factors :

1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.

Oxygen Uptake in the Lungs is Increased About 70X by Hemoglobin in the Red Cells

• In the lungs oxygen must enter the blood
• A small amount of oxygen dissolves directly in the serum, but 98.5% of the oxygen is carried by hemoglobin
• All of the hemoglobin is found within the red blood cells (RBCs or erythrocytes)
• The hemoglobin content of the blood is about 15 gm/deciliter (deciliter = 100 mL)
• Red cell count is about 5 million per microliter

Each Hemoglobin Can Bind Four O₂ Molecules (100% Saturation)

• Hemoglobin is a protein molecule with 4 protein sub-units (2 alphas and 2 betas)
  • Each of the 4 sub-units contains a heme group which gives the protein a red color
  • Each heme has an iron atom in the center which can bind an oxygen molecule (O2)
  • The 4 hemes in a hemoglobin can carry a maximum of 4 oxygen molecules
• When hemoglobin is saturated with oxygen it has a bright red color; as it loses oxygen it becomes bluish (cyanosis)

The Normal Blood Hematocrit is Just Below 50%

• Blood consists of cells suspended in serum
• More than 99% of the cells in the blood are red blood cells designed to carry oxygen
  • 25% of all the cells in the body are RBCs
• The volume percentage of cells in the blood is called the hematocrit
• Normal hematocrits are about 40% for women and 45% for men

At Sea Level the Partial Pressure of O₂ is High Enough to Give Nearly 100% Saturation of Hemoglobin

• As the partial pressure of oxygen in the alveoli increases the hemoglobin in the red cells passing through the lungs rises until the hemoglobin is 100% saturated with oxygen
  • At 100% saturation each hemoglobin carries 4 O₂ molecules
  • This is equal to 1.33 mL O₂ per gram of hemoglobin
• A person with 15 gm Hb/deciliter can carry:
  • Max O₂ carriage = 1.33 mL O₂/gm X 15 gm/deciliter = 20 mL O₂/deciliter
• A plot of % saturation vs pO2 gives an S-shaped "hemoglobin dissociation curve"
• At 100% saturation each hemoglobin binds 4 oxygen molecules

At High Altitudes Hemoglobin Saturation May be Well Below 100%

• At the alveolar pO₂ of 105 mm Hg at sea level the hemoglobin will be about 97% saturated, but the saturation will fall at high altitudes
• At 12,000 feet altitude alveolar pO₂ will be about 60 mm Hg and the hemoglobin will be 90% saturated
• At 29,000 feet (Mt. Everest) alveolar pO₂ is about 24 mm Hg and the hemoglobin will be only 42% saturated
• At very high altitudes most climbers must breath pure oxygen from tanks
• During acclimatization to high altitude the hematocrit can rise to about 60%- this increases the amount of oxygen that can be carried
• Hematocrits above 60% are not useful because the blood viscosity will increase to the point where it impairs circulation

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