Monday, March 31, 2008

Electrical Activity of the Heart and ECGs

At rest, the heart muscle is polarized. This means that the cells are negatively charged on the inside and positively charged on the outside, due to different concentrations of ions on the inside and outside. These ions include sodium and potassium (most important), calcium and chloride.

The heart must depolarize before it can contract, which means ths insides of the cells must become positively charged and the outsides must become negatively charged. This depolarization is caused by an increase in the conductance of sodium across the membrane. The sodium brings with it calcium, to activate the contractile proteins. When the impulse spreads through transverse tubules (T-tubules) from the sarcolemma to calcium storage sites in the sarcoplasmic reticulum (membrane tubes near the sarcomeres, which cause contraction), calcium ions are released and cause contraction. Once the contraction is complete, the calcium is pumped back into the storage sites. During this phase, repolarization, the cells return to their resting action potentials. Potassium conductivity increases and the movement of sodium and calcium into the cell slows down.

An electocardiogram (ECG) measures the differences in membrane potentials on the heart's surface by determining the difference between 2 electrodes placed on the body's surface.

The SA node creates an impulse that carries a wave of depolarization over both atria. This is the p-wave. It immediately precedes atrial contraction and allows for simultaneous contraction of the left and right atria.

Once the impulse reaches the AV node, there is a slight delay to allow for blood to pass through the AV valve. Once the AV node is stimulated, the ventricles depolarize, creating the QRS complex.

The impulse then enters the AV Bundle, left and right bundle branches and purkinje fibers, which allow for rapid stimulation of the ventricular muscles. The contraction of the ventricles occur just after the appearance of the QRS complex. Atrial repolarization occurs at this time, but is usually hidden by the QRS complex on ECGs.

The T-wave represents the repolarization of the ventricles, just after ventricular contraction. The ST segment appears between the S and T wave, and detects deficiencies in coronary artery blood flow.

A refractory period occurs after contraction of cardiac muscle. During this time, the muscle is incapable of a full contraction, and an attempt at depolarization during this interval results in a reduced force of cardiac contraction.

Training's effects on ECG
Appearance of sinus bradycardia- Trained athletes have reduced resting heart rates. This is probably due to reduced stimulation from the sympathetic nervous system and increased stimulation from the parasympathetic nervous system. Also, a lower intrinsic heart rate may contribute to the lower RHR.

Other disturbances that may be visible in the ECGs of athletes include: AV conduction delays, wandering atrial pacemaker, ST segment elevation, T-wave inversion, substitute of the AV node as primary pacemakes. These are also common in those with ischemic heart disease. Athletes tend to have an increased stimulation of parasympathetic influences from the vagus nerve, which can disappear during exercise since parasympathetic stimulation decreases and sympathetic stimulation increases during exercise.

Sunday, March 30, 2008

Atherosclerosis

Atherosclerosis is a form of arteriosclerosis, which involves the build-up of plaque. 60-70% of build-ups cause an MI to occur, but most fatal heart attacks result from a 40% blockage.

Plaque formed on vessel walls crack or break, causing the fibrous cap (scab) to break as well. The contents of the plaque are released into the bloodstream, causing a clot to develop. The clot moves through smaller blood vessels and ends up blocking the bloodstream. This clot is called a thrombus.

Thrombolytic drugs can dissolve clots if administered within 2-6 hours, but most people don't want to go to the Emergency Room.

Atherosclerosis is the accumulation of lipids and other substances in the innermost lining of the blood vessel wall, the endothelial cells. These lipids are not an isolated thing- everyone has some. They start in childhood but manifest in adulthood, becoming visible to the naked eye by age 3.

The "Injury Theory" suggests that an unknown injury occurs at the endothelial cells. A monocyte, white blood cell, moves to the area and can be trapped under the lining due to a disconnect in the endothelial cell. Possibly an inflammatory response occurs, which attracts more monocytes to the area.

The monocytes become macrophages, which swallow other things including lipids and LDL. The macrophages then become foam cells, which are a component of the fatty streak. As the accumulation develops under the blood vessel wall, smooth muscle surrounds the blood vessel and allows vasocontriction and vasodilation. Macrophages release a signal for reinforcement and smooth muscle cells and LDL come to the site, as well as clotting factors that initiate a clot.

The accumulation bulges out into the blood vessel and reduces flow. A fibrous cap forms that covers it. It may crack or break open, then form a clot in a smaller blood vessel.

CV Responses to Acute Exercise

Increased heart rate (linear) as a direct function of the SA Nore. Neural control starts to lose predominance as the intensity of exercises increases. No change with maximal heart rate.
Increased stroke volume. Affected by heart rate, preload, afterload, contractility.

troke volume increases until about 40-60% of maximum capacity, then levels off. Per Gladhill, stroke volume does not plateau in endurance athletes. Postmenopausal women may hit a peak, then decline. Stroke volume is the factor that separates the athlete from the non-athlete. If there is a plateau, then an increase in Cardac Output is the result of an increase in heart rate.


Systolic blood pressure increases with exercise because cardiac output increases, which means more blood is being pumped out of the heart. The diastolic blood pressure does not change much - draining through the system. Changes in the diastolic blood pressure greater than 10mm Hg is reason to stop exercising.

Mean arterial pressure is the average of the systolic and diastolic blood pressure, and describes the average driving pressure for movement of blood. Since the heart is in diastole for 2/3 of each beat, then MAP is determined calculating DBP + 1/3(SBP-DBP).

Total Peripheral Resistance decreases with exercise.

av-O2 Difference is the difference between the amount of oxygen in the arteries and the amount of oxygen in the veins. This tells us how efficiently the muscles are extracting and using oxygen. During exercise, this difference increases.

Saturday, March 29, 2008

Krebs Cycle and Electron Transport Chain

Describes the specific metabolic pathway within cells to account for oxidation of basic food components (carbohydrates, fat, protein) for energy. The reactions all occur within the mitochondria of the cells.

Acetyl CoA can be formed from glucose metabolism, fatty acid metabolism, or amino acid metabolism. No matter how it was formed, the majority of it goes into the Citric Acid, or Krebs Cycle.

Acetyl CoA splits off a coenzyme A group. This releases bond energy to power the next reaction. The acetyl group couples to oxaloacetate, resulting in the formation of citrate, which then undergoes a series of conversions. The final product of these conversions is oxaloacetate. This allows for incoming Acetyl CoA and the cycle is repeated. The acetyl group is completely oxidised to form 2 carbon dioxide molecules. One of these reactions produces GTP, which is converted to ATP. Four of these reactions are oxidative reactions; 3 where NAD acts as the electron acceptor, and 1 where FAD acts as the electron acceptor. Since the supply of oxidised cofactors is limited, NADH and FADH must be re-oxidised, which is where the electron transport chain comes into play.

The purpose of the electron transport chain is to reoxidise NADH and FADH to NAD and FAD, respectively. This occurs through a series of oxidations/reduction reactions, producing bond energy harnessed to the reaction of the production of ATP and water. 3 ATP are produced for every NADH involved, and 2 ATP are produced for every FADH involved. Oxygen is the final electron acceptor, producing water.

Fat Metabolism

Adenosine Triphosphate (ATP) is a compound used to exchange or supply energy for endergonic processes. Endergonic processes are those in which energy is absorbed in the form of work- energy is required and leads to the formation of molecular bonds, which results in decreased entropy (useless energy). ATP is hydrolysed by either removing 1 terminal phosphate (ATP ---> ADP + Pi) or removing 2 terminal phosphates (ATP ---> AMP + Pi).

Skeletal muscles are very efficient at converting chemical energy into mechanical energy with little waste (30-50%). ATP is regenerated from Creatine Phosphate during exercise. Creatine Phophate can quickly release a phosphate group, which can react with ADP to create the ATP necessary for muscle contraction. At rest, normal cell metabolism resynthesises ATP, which in turn resynthesises Creatine Phosphate.

Dietary fat is digested, then stored as triglycerides, which is the major fuel source stored in the body. A triglyceride is a glycerol molecule with 3 fatty acids attached. Triglycerides are non-polar (meaning there is equal sharing of electrons between two atoms). Chlyomicrons are large lipoprotein particles that give the triglycerides a polar coat and transport them to adipose tissue. The enzyme lipoprotein lipase is stimulated by insulin and stores the triglyceride in the adipose tissue.

The release of triglycerides from fatty tissue, when needed, is catalyzed by the enzyme mobilisng lipase, which is stimulated by glucagon and adrenaline. The triglycerides are transported via attachment to the major protein in circulation, albumin, to the tissue for oxidation.

Triglycerides make up about 70% of the body's energy reserves due to the efficiency with which they are stored and their ability to be highly reduced. Since they are anhydrous (stored without water due to their non-polar nature), triglycerides tend to be compact and light. Vast quantities of triglycerides can be stored in less space. Since they are a largely hydrocarbon chain (16-20 covalently linked methyl groups), they are highly reduced and capable of yielding a large supply of energy (40 J/g as compared to 18 J/g glycogen).

B-Oxidation of Fatty Acids occurs within the mitochondria of the liver and muscles. During sustained exercise, this cyclic chain provides a major source of energy in slow-twitch muscles. Each cycle of this chain of reactions results in 2 carbohydrates hydrolysed into molecules of Acetyl CoA from a fatty acid chain. Each cycle of the chain also contains NAD ---> NADH and FAD ---> FADH. The NADH and FADH are then oxidised to the electron transport chain and coupled with ATP production, while the Acetyl CoA molecules are converted into CO2 in the Citric Acid Cycle, then participate in the electron transport chain, coupled with ATP production.

Ketone Bodies are 4-carbon units that are oxidised in an alternate method of using Acetyl CoA formed in B-oxidation. In this process, Acteyl CoA is converted to acetoacetate in the liver, then further reduced to b-hydroxybutyrate. Acetoacetate is preferred as a source of energy over glucose by heart muscle and the renal cortex. The brain prefers glucose, but can use acetoacetate if necessary, as during starvation. Fatty acids can't enter neural tissue, so acetoacetate is regarded as a water-soluble, easily-transportable version of Acetyl CoA. The efficiency of this mechanism as compared to B-oxidation is comparable.

Fatty Acid Synthesis occurs in the cytoplasm of cells. Cyclic reactions occur, resulting in the conversion of Acteyl CoA to 2-carbon units added to the fatty acid chain. This supplies fatty acids that are needed by the body but not supplied through the diet. The purpose of fatty acid synthesis is to convert excess dietary glucose to fatty acids for storage. Glucose is converted to Pyruvate through glycolysis, then to Acteyl CoA. If ATP is required, then Acetyl CoA is oxidised via the Citric Acid Cycle. If glucose intake exceeds the body's needs, then the Acetyl CoA is used in fatty acid synthesis in the liver or is stored as triglycerides in the adipose tissue.

The drawback to fat metabolism is that it requres oxygen. If energy is needed faster than oxygen can be delivered to the working muscles, then they switch to one of the less-efficient anaerobic pathways.

ATP - Adenosine Triphosphate. 1 phosphate ---> 7.3 kcal/mole

NADH - Nicotinamide Adenine Dinucleotide. Can transfer 2 electrons and 1 hydrogen ion to oxygen. --->52 kcal/mole.....3 ATP formed.

FADH2 - Flavin Adenine Dinucleotide. 43.4 kcal/mole......2 ATP formed.