DNA (Deoxyribonucleic acid) - controls cell function via transcription and translation (in other words, by controlling protein synthesis in a cell)

Transcription - DNA is used to produce mRNA

Translation - mRNA then moves from the nucleus into the cytoplasm & is used to produce a protein . requires mRNA, tRNA (transfer RNA), amino acids, & a ribosome

tRNA molecule

• sequence of amino acids in a protein is determined by sequence of codons (mRNA). Codons are 'read' by anticodons of tRNAs & tRNAs then 'deliver' their amino acid.
• Amino acids are linked together by peptide bonds (see diagram to the right)
• As mRNA slides through ribosome, codons are exposed in sequence & appropriate amino acids are delivered by tRNAs. The protein (or polypeptide) thus grows in length as more amino acids are delivered.
• The polypeptide chain then 'folds' in various ways to form a complex three-dimensional protein molecule that will serve either as a structural protein or an enzyme.

Principal heart sounds

1. S1: closure of AV valves;typically auscultated as a single sound 

Clinical note: In certain circumstances, S1 may be accentuated. This occurs when the valve leaflets are “slammed” shut in early systole from a greater than normal distance because they have not had time to drift closer together. Three conditions that can result in an accentuated S1 are a shortened PR interval, mild mitral stenosis, and high cardiac-output states or tachycardia.

2. S2: closure of semilunar valves in early diastole , normally “split” during inspiration . S2: best appreciated in the 2nd or 3rd left intercostal space

Clinical note: Paradoxical or “reversed” splitting occurs when S2 splitting occurs with expiration and disappears on inspiration. Moreover, in paradoxical splitting, the pulmonic valve closes before the aortic valve, such that P2 precedes A2. The most common cause is left bundle branch block (LBBB). In LBBB, depolarization of the left ventricle is impaired, resulting in delayed left ventricular contraction and aortic valve closure.

3. S3: ventricular gallop, presence reflects volume-overloaded state 
 
 Clinical note: An S3 is usually caused by volume overload in congestive heart failure. It can also be associated with valvular disease, such as advanced mitral regurgitation, in which the “regurgitated” blood increases the rate of ventricular filling during early diastole.
 
4. S4: atrial gallop, S4: atrial contraction against a stiff ventricle, often heard after an acute myocardial infarction.

Clinical note: An S4 usually indicates decreased ventricular compliance (i.e., the ventricle does not relax as easily), which is commonly associated with ventricular hypertrophy or myocardial ischemia. An S4 is almost always present after an acute myocardial infarction. It is loudest at the apex with the patient in the left lateral decubitus position (lying on their left side).

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

Carbon Dioxide Transport

Carbon dioxide (CO₂) combines with water forming carbonic acid, which dissociates into a hydrogen ion (H⁺) and a bicarbonate ions:

CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻

95% of the CO₂ generated in the tissues is carried in the red blood cells:

• It probably enters (and leaves) the cell by diffusing through transmembrane channels in the plasma membrane. (One of the proteins that forms the channel is the D antigen that is the most important factor in the Rh system of blood groups.)
• Once inside, about one-half of the CO₂ is directly bound to hemoglobin (at a site different from the one that binds oxygen).
• The rest is converted — following the equation above — by the enzyme carbonic anhydrase into
  • bicarbonate ions that diffuse back out into the plasma and
  • hydrogen ions (H⁺) that bind to the protein portion of the hemoglobin (thus having no effect on pH).

Only about 5% of the CO₂ generated in the tissues dissolves directly in the plasma. (A good thing, too: if all the CO₂ we make were carried this way, the pH of the blood would drop from its normal 7.4 to an instantly-fatal 4.5!)

When the red cells reach the lungs, these reactions are reversed and CO₂ is released to the air of the alveoli.

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 
 

Bile - produced in the liver and stored in the gallbladder, released in response to CCK . Bile salts (salts of cholic acid) act to emulsify fats, i.e. to split them so that they can mix with water and be acted on by lipase.

Pancreatic juice: Lipase - splits fats into glycerol and fatty acids. Trypsin, and chymotrypsin - protease enzymes which break polypeptides into dipeptides. Carboxypeptidase - splits dipeptide into amino acids. Bicarbonate - neutralizes acid. Amylase - splits polysaccharides into shorter chains and disaccharides.

Intestinal enzymes (brush border enzymes): Aminopeptidase and carboxypeptidase - split dipeptides into amino acids. Sucrase, lactase, maltase - break disaccharides into monosaccharides. Enterokinase - activates trypsinogen to produce trypsin. Trypsin then activates the precursors of chymotrypsin and carboxypeptidase. Other carbohydrases: dextrinase and glucoamylase. These are of minor importance.