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.

A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.

Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.

Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.

Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.

Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects 

Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.

1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.

2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.

3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.

4) Ventricular repolarization occurs.

The cell membrane is called the sarcolemma. This membrane is structured to receive and conduct stimuli. The sarcoplasm of the cell is filled with contractile myofibrils and this results in the nuclei and other organelles being relegated to the edge of the cell.

Myofibrils are contractile units within the cell which consist of a regular array of protein myofilaments. Each myofilament runs longitudinally with respect to the muscle fiber. There are two types: the thick bands and the thin bands. Thick bands are made of multiple molecules of a protein called myosin. The thin bands are made of multiple molecules of a protein called actin. The thin actin bands are attached to a Z-line or Z-disk of an elastic protein called titin. The titin protein also extends into the myofibril anchoring the other bands in position. From each Z-line to the next is a unit called the 

    The sarcomere is the smallest contractile unit in the myofibril. Sarcomeres contract because the Z-lines move closer together. As the sarcomeres contract the myofibrils contract. As the myofibrils contract the muscle cell contracts. And as the cells contract the entire muscle contracts.

The arrangement of the thick myosin filaments across the myofibrils and the cell causes them to refract light and produce a dark band known as the A Band. In between the A bands is a light area where there are no thick myofilaments, only thin actin filaments. These are called the I Bands. The dark bands are the striations seen with the light microscope.

Membrane Potential

• Membrane potentials will occur across cell membranes if
  • 1) there is a concentration gradient of an ion
  • 2) there is an open channel in the membrane so the ion can move from one side to the other

The Sodium Pump Sets Up Gradients of Na and K Across Cell Membranes

• All cells have the Na pump in their membranes
  • Pumps 3 Nas out and 2 Ks in for each cycle
  • Requires energy from ATP
    • Uses about 30% of body's metabolic energy
  • This is a form of active transport- can pump ions "uphill", from a low to a high concentration
  • This produces concentration gradients of Na & K across the membrane
  • Typical concentration gradients:

•  
• The ion gradients represent stored electrical energy (batteries) that can be tapped to do useful work
• The Na pump is of ancient origin, probably originally designed to protect cell from osmotic swelling

Inhibited by the arrow poisons ouabain and digitalis

Biological Functions are Extremely Sensitive to pH

• H+ and OH- ions get special attention because they are very reactive
• Substance which donates H+ ions to solution = acid
• Substance which donates OH- ions to solution = base
• Because we deal with H ions over a very wide range of concentration, physiologists have devised a logarithmic unit, pH, to deal with it
  • pH = - log [H⁺]
  • [H⁺] is the H ion concentration in moles/liter
  • Because of the way it is defined a high pH indicates low H ion and a low pH indicates high H ion- it takes a while to get used to the strange definition
  • Also because of the way it is defined, a change of 1 pH unit means a 10X change in the concentration of H ions
    • If pH changes by 2 units the H+ concentration changes by 10 X 10 = 100 times

• Human blood pH is 7.4
  • Blood pH above 7.4 = alkalosis
  • Blood pH below 7.4 = acidosis
• Body must get rid of ~15 moles of potential acid/day (mostly CO₂)
  • CO₂ reacts with water to form carbonic acid (H₂CO₃)
  • Done mostly by lungs & kidney
• In neutralization H⁺ and OH^- react to form water
• If the pH changes charges on molecules also change, especially charges on proteins
  • This changes the reactivity of proteins such as enzymes
• Large pH changes occur as food passes through the intestines.

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