Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

• consists of four polypeptides:
  • two alpha (α) chains of 141 amino acids and
  • two beta (β) chains of 146 amino acids
• Each of these is attached the prosthetic group heme.
• There is one atom of iron at the center of each heme.
• One molecule of oxygen can bind to each heme.

The reaction is reversible.

• Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated hemoglobin of the venous blood becomes the bright-red oxyhemoglobin of the arterial blood.
• Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin gives up its oxygen.

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).

The Posterior Lobe

The posterior lobe of the pituitary releases two hormones, both synthesized in the hypothalamus, into the circulation.

• Antidiuretic Hormone (ADH).
  ADH is a peptide of 9 amino acids. It is also known as arginine vasopressin. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood.
  • A deficiency of ADH
    • leads to excessive loss of urine, a condition known as diabetes  nsipidus.
• Oxytocin
  Oxytocin is a peptide of 9 amino acids. Its principal actions are:
  • stimulating contractions of the uterus at the time of birth
  • stimulating release of milk when the baby begins to suckle

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO₂ + H₂O <==> H₂CO₃ <==> H⁺ + HCO₃-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H⁺, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO₃- binds to H⁺
high pH     →   H₂CO₃ releases H⁺
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H⁺)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H⁺)

Proteinuria—Protein content in urine, often due to leaky or damaged glomeruli.

Oliguria—An abnormally small amount of urine, often due to shock or kidney damage.

Polyuria—An abnormally large amount of urine, often caused by diabetes.

Dysuria—Painful or uncomfortable urination, often from urinary tract infections.

Hematuria—Red blood cells in urine, from infection or injury.

Glycosuria—Glucose in urine, due to excess plasma glucose in diabetes, beyond the amount able to be reabsorbed in the proximal convoluted tubule.

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