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
 

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.

Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)

• Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions):

• Alveoli
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Alveolar capillaries
  • Entering the alveolar capillaries
    • PO₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
    • PCO₂ = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 

• While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

• Leaving the alveolar capillaries
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
• • Entering the systemic capillaries
    • PO₂ = 100 mm Hg
    • PCO₂ = 40 mm Hg
  • Body cells (resting conditions)
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
• • Leaving the systemic capillaries
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Plasma:  is the straw-colored liquid in which the blood cells are suspended.

Plasma transports materials needed by cells and materials that must be removed from cells:

• various ions (Na⁺, Ca²⁺, HCO₃⁻, etc.
• glucose and traces of other sugars
• amino acids
• other organic acids
• cholesterol and other lipids
• hormones
• urea and other wastes

Most of these materials are in transit from a place where they are added to the blood

• exchange organs like the intestine
• depots of materials like the liver

to places where they will be removed from the blood.

• every cell
• exchange organs like the kidney, and skin.

Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO₂) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O₂  <= === => HbO₂ + H+

3.    binding gets more efficient as each O₂ binds
4.    release gets easier as each O₂ is released

5.    Several factors regulate AFFINITY of O₂

a.    Partial Pressure of O₂
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O₂

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O₂ unloaded

C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

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.