COPD and Cancer

A.    Chronic Obstructive Pulmonary Disease (COPD)

1.    Common features of COPD

a.    almost all have smoking history
b.    dyspnea - chronic "gasping" for air
c.    frequent coughing and infections
d.    often leads to respiratory failure

2.    obstructive emphysema - usually results from smoking

a.    enlargement & deterioration of alveoli
b.    loss of elasticity of the lungs
c.    "barrel chest" from bronchiole opening during inhalation & constriction during exhalation

3.    chronic bronchitis - mucus/inflammation of mucosa

B.    Lung Cancer

1.    squamous cell carcinoma (20-40%) - epithelium of the bronchi and bronchioles
2.    adenocarcinoma (25-35%) - cells of bronchiole glands and cells of the alveoli
3.    small cell carcinoma (10-20%) - special lymphocyte-like cells of the bronchi
4.    90% of all lung cancers are in people who smoke or have smoked 
 

The Nervous System Has Peripheral and Central Units

• The central nervous system (CNS) is the brain and spinal column
• The peripheral nervous system (PNS) consists of nerves outside of the CNS
• There are 31 pairs of spinal nerves (mixed motor & sensory)
• There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

The Nervous System Has Peripheral and Central Units

• The central nervous system (CNS) is the brain and spinal column
• The peripheral nervous system (PNS) consists of nerves outside of the CNS
• There are 31 pairs of spinal nerves (mixed motor & sensory)
• There are 12 pairs of cranial nerves (some are pure sensory, but most are mixed)

The pattern of innervation plotted on the skin is called a dermatome

Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .

To understand the pathophysiology  of the heart failure ,  lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume

Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload    (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .

Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .

Contractility : Reducing the power of contraction such as in  myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .

Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.

Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility  . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff  .

The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .
 

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 
 

Bile contains:

• bile acids. These amphiphilic steroids emulsify ingested fat. The hydrophobic portion of the steroid dissolves in the fat while the negatively-charged side chain interacts with water molecules. The mutual repulsion of these negatively-charged droplets keeps them from coalescing. Thus large globules of fat (liquid at body temperature) are emulsified into tiny droplets (about 1 µm in diameter) that can be more easily digested and absorbed.

• bile pigments. These are the products of the breakdown of hemoglobin removed by the liver from old red blood cells. The brownish color of the bile pigments imparts the characteristic brown color of the feces.

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.