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Physiology

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.

Functions

Manufacture - blood proteins - albumen, clotting proteins , urea - nitrogenous waste from amino acid metabolism , bile - excretory for the bile pigments, emulsification of fats by bile salts

Storage - glycogen , iron - as hemosiderin and ferritin , fat soluble vitamins A, D, E, K

Detoxification -alcohol , drugs and medicines , environmental toxins

Protein metabolism -

  • transamination - removing the amine from one amino acid and using it to produce a different amino acid. The body can produce all but the essential amino acids; these must be included in the diet.
  • deamination - removal of the amine group in order to catabolize the remaining keto acid. The amine group enters the blood as urea which is excreted through the kidneys.

Glycemic Regulation - the management of blood glucose.

  • glycogenesis - the conversion of glucose into glycogen.
  • glycogenolysis - the breakdown of glycogen into glucose.

gluconeogenesis - the manufacture of glucose from non carbohydrate sources, mostly protein

Control of processes in the stomach:

The stomach, like the rest of the GI tract, receives input from the autonomic nervous system. Positive stimuli come from the parasympathetic division through the vagus nerve. This stimulates normal secretion and motility of the stomach. Control occurs in several phases:

Cephalic phase stimulates secretion in anticipation of eating to prepare the stomach for reception of food. The secretions from cephalic stimulation are watery and contain little enzyme or acid.

Gastric phase of control begins with a direct response to the contact of food in the stomach and is due to stimulation of pressoreceptors in the stomach lining which result in ACh and histamine release triggered by the vagus nerve. The secretion and motility which result begin to churn and liquefy the chyme and build up pressure in the stomach. Chyme surges forward as a result of muscle contraction but is blocked from entering the duodenum by the pyloric sphincter. A phenomenon call retropulsion occurs in which the chyme surges backward only to be pushed forward once again into the pylorus. The presence of this acid chyme in the pylorus causes the release of a hormone called gastrin into the bloodstream. Gastrin has a positive feedback effect on the motility and acid secretion of the stomach. This causes more churning, more pressure, and eventually some chyme enters the duodenum.

Intestinal phase of stomach control occurs. At first this involves more gastrin secretion from duodenal cells which acts as a "go" signal to enhance the stomach action already occurring. But as more acid chyme enters the duodenum the decreasing pH inhibits gastrin secretion and causes the release of negative or "stop" signals from the duodenum.

These take the form of chemicals called enterogastrones which include GIP (gastric inhibitory peptide). GIP inhibits stomach secretion and motility and allows time for the digestive process to proceed in the duodenum before it receives more chyme. The enterogastric reflex also reduces motility and forcefully closes the pyloric sphincter. Eventually as the chyme is removed, the pH increases and gastrin and the "go" signal resumes and the process occurs all over again. This series of "go" and "stop" signals continues until stomach emptying is complete.

  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

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.

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

Concentration versus diluting urine 

Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.                   
                                                   
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.

In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.

If plasma is hypotonic ADH will be inhibited and the diluted urine in distal  tubules will be excreted as diluted urine.

Urea  contributes to concentrating and diluting of urine as follows:

Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.

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