1. PATHOPHYSIOLOGY OF THE CONDUCTION SYSTEM


2. Cardiac arrhythmias = deviation from normal rate, rhythm

    

   1. Heart block (types) = conduction system damage
      1. Complete Heart Block = 3rd degree block
         1. idioventricular beat (35-45/min)
         2. Atria at normal sinus rhythm
         3. Periods of asystole (dizziness, fainting)
         4. Causes = myocardial infarction of ventricular septum, surgical correction of interseptal defects, drugs
      2. Incomplete Heart Block = 2nd degree block
         1. Not all atrial beats reach ventricle
         2. Ventricular beat every 2nd, 3rd, etc. atrial beat, (2:1 block, 3:1 block)
      3. Incomplete Heart Block = 1st degree block
         1. All atrial beats reach ventricle
         2. PR interval abnormally long = slower conduction
      4. Bundle branch blocks (right or left)
         1. Impulses travel down one side and cross over
         2. Ventricular rate normal, QRS prolonged or abnormal
   2. Fibrillation
      1. Asynchronous contractions = twitching movements
      2. Loss of synchrony = little to No output
      3. Atrial Fibrillation
         1. Irregular ventricular beat & depressed pumping efficiency
         2. Atrial beat = 125 - 150/min, pulse feeble = 60 - 70/min
         3. Treatment = Digitalis - reduces rate of ventricular contraction, reduces pulse deficit
      4. Ventricular Fibrillation
         1. Almost no blood pumped to systemic system
         2. ECG = extremely bizarre
         3. Several minutes = fatal
         4. Treatment = defibrillation, cardiac massage can maintain some cardiac output

Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process. Urine formation occurs during three processes:

Filtration

Reabsorption

Secretion

Filtration

During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.

Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows through the rest of the body to facilitate tissue perfusion and gas exchange.

Reabsorption

The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The fluid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.

Secretion

During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular filtration or tubular reabsorbtion.

AdenosineTriphosphate (ATP)

• Animal cells cannot directly use most forms of energy
  • Most cellular processes require energy stored in the bonds of a molecule, adenosine triphosphate (ATP)
  • ATP is referred to as the energy currency of the cell

It is a nucleotide, formed from:

• the base adenine (the structure with 2 rings),
• the 5 carbon sugar deoxyribose (one ring)
• 3 phosphates

Energy is stored in the bonds between the phosphates and is released when the bonds are broken

The thyroid gland is a double-lobed structure located in the neck. Embedded in its rear surface are the four parathyroid glands.

The Thyroid Gland

The thyroid gland synthesizes and secretes:

• thyroxine (T₄) and
• calcitonin

T₄ and T₃

Thyroxine (T₄ ) is a derivative of the amino acid tyrosine with four atoms of iodine. In the liver, one atom of iodine is removed from T₄ converting it into triiodothyronine (T₃). T₃ is the active hormone. It has many effects on the body. Among the most prominent of these are:

• an increase in metabolic rate
• an increase in the rate and strength of the heart beat.

The thyroid cells responsible for the synthesis of T₄ take up circulating iodine from the blood. This action, as well as the synthesis of the hormones, is stimulated by the binding of TSH to transmembrane receptors at the cell surface.

Diseases of the thyroid

1. hypothyroid diseases; caused by inadequate production of T₃

• cretinism: hypothyroidism in infancy and childhood leads to stunted growth and intelligence. Can be corrected by giving thyroxine if started early enough.
• myxedema: hypothyroidism in adults leads to lowered metabolic rate and vigor. Corrected by giving thyroxine.
• goiter: enlargement of the thyroid gland. Can be caused by:
  • inadequate iodine in the diet with resulting low levels of T₄ and T₃;
  • an autoimmune attack against components of the thyroid gland (called Hashimoto's thyroiditis).

2. hyperthyroid diseases; caused by excessive secretion of thyroid hormones

Graves´ disease. Autoantibodies against the TSH receptor bind to the receptor mimicking the effect of TSH binding. Result: excessive production of thyroid hormones. Graves´ disease is an example of an autoimmune disease.

Osteoporosis. High levels of thyroid hormones suppress the production of TSH through the negative-feedback mechanism mentioned above. The resulting low level of TSH causes an increase in the numbers of bone-reabsorbing osteoclasts resulting in osteoporosis.

Calcitonin

Calcitonin is a polypeptide of 32 amino acids. The thyroid cells in which it is synthesized have receptors that bind calcium ions (Ca²⁺) circulating in the blood. These cells monitor the level of circulating Ca²⁺. A rise in its level stimulates the cells to release calcitonin.

• bone cells respond by removing Ca²⁺ from the blood and storing it in the bone
• kidney cells respond by increasing the excretion of Ca²⁺

Both types of cells have surface receptors for calcitonin.

Because it promotes the transfer of Ca²⁺ to bones, calcitonin has been examined as a possible treatment for osteoporosis

Hemostasis - the  stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:

1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.

2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.

3) Formation of the Blood Clot:

A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.

B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.

C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.

The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.

Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.

Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.

Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are  VIII, IX, and XI.

Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage

A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:

• relaxing arterioles
• inhibiting the secretion of renin and aldosterone
• inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.

The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.

The Heartbeat

During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.

The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.

The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.

When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.

The contraction of the heart in response to this electrical activity creates systole.

A period of recovery follows called diastole.

• The heart muscle and S-A node become recharged.
• The heart muscle relaxes.
• The atria refill. 

The Electrocardiogram

The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG

Control of the Heart

Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.

• One sends nerve impulses down accelerator nerves.
• The other sends nerve impulses down a pair of vagus nerves

Accelerator Nerves

The accelerator nerves are part of the sympathetic branch of the autonomic nervous system, and  like all post-ganglionic sympathetic neurons  release noradrenaline at their endings on the heart.

They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.

Vigorous exercise accelerates heartbeat in two ways;

• As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay  by the accelerator nerves  to the heart.
• As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.

Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure

The Vagus Nerves

The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.

Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these  by way of the vagus nerves  to the heart. Heartbeat and blood pressure diminish.