HEART DISORDERS

1. Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
   1. Renin release (Juxtaglomerular cells) Kidney
   2. Converts Angiotensinogen => Angiotensin I
   3. In lungs Angiotensin I Converted => Angiotensin II
   4. Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
      1. stimulates thirst
      2. stimulates adrenal cortex to release Aldosterone
         (Sodium retention, potassium loss)
      3. stimulates kidney directly to reabsorb Sodium
      4. releases ADH from Posterior Pituitary
2. Myocardial Infarction

    

   1. Myocardial Cells die from lack of Oxygen
   2. Adjacent vessels (collateral) dilate to compensate
   3. Intracellular Enzymes leak from dying cells (Necrosis)
      1. Creatine Kinase CK (Creatine Phosphokinase) 3 forms
         1. One isoenzyme = exclusively Heart (MB)
         2. CK-MB blood levels found 2-5 hrs, peak in 24 hrs
         3. Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
      2. Serum glutamic oxaloacetic transaminase (SGOT)
         1. Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
         2. SGOT returns to normal after 3-4 days
   4. Myocardium weakens = Decreased CO & SV (severe - death)
   5. Infarct heal by fibrous repair
   6. Hypertrophy of undamaged myocardial cells
      1. Increased contractility to restore normal CO
      2. Improved by exercise program
   7. Prognosis
      1. 10% uncomplicated recovery
      2. 20% Suddenly fatal
      3. Rest MI not fatal immediately, 15% will die from related causes
3. Congenital heart disease (Affect oxygenation of blood)
   1. Septal defects
   2. Ductus arteriosus
   3. Valvular heart disease
      1. Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
      2. Regurgitation = cusps, retracted, Do not close, blood moves backwards

Neurophysiology

Transmission of an action potential. This occurs in two ways:

1) across the synapse - synaptic transmission. This is a chemical process, the result of a chemical neurotransmitter.

2) along the axon - membrane transmission. This is the propagation of the action potential itself along the membrane of the axon.

Synaptic transmission - What you learned about the neuromuscular junction is mostly applicable here as well. The major differences in our current discussion are:

1) Transmission across the synapse does not necessarily result in an action potential. Instead, small local potentials are produced which must add together in summation to produce an action potential.

2) Although ACh is a common neurotransmitter, there are many others and the exact effect at the synapse depends on the neurotransmitter involved.

3) Neurotransmitters can be excitatory or inhibitory. The result might be to turn off the next neuron rather than to produce an action potential

The basic steps of synaptic transmission are the same as described at the neuromuscular junction

1) Impulse arrives at the axon terminus causing opening of Ca²⁺ channels and allows Ca²⁺  to enter the axon. The calcium ions are in the extracellular fluid, pumped there much like sodium is pumped. Calcium is just an intermediate in both neuromuscular and synaptic transmission.

2) Ca²⁺  causes vesicles containing neurotransmitter to release the chemical into the synapse by exocytosis across the pre-synaptic membrane.

3) The neurotransmitter binds to the post-synaptic receptors. These receptors are linked to chemically gated ion channels and these channels may open or close as a result of binding to the receptors to cause a graded potential which can be either depolarization, or hyperpolarization depending on the transmitter. Depolarization results from opening of Na⁺ gates and is called an EPSP. Hyperpolarization could result from opening of K⁺ gates and is called IPSP. 

4) Graded potentials spread and overlap and can summate to produce a threshold depolarization and an action potential when they stimulate voltage gated ion channels in the neuron's trigger region.

5) The neurotransmitter is broken down or removed from the synapse in order for the receptors to receive the next stimulus. As we learned there are enzymes for some neurotransmitters such as the Ach-E which breaks down acetylcholine. Monoamine oxidase (MAO) is an enzyme which breaks down the catecholamines (epinephrine, nor-epinephrine, dopamine) and nor-epinephrine (which is an important autonomic neurotransmitter) is removed by the axon as well in a process known as reuptake. Other transmitters may just diffuse away.

Graded Potentials - these are small, local depolarizations or hyperpolarizations which can spread and summate to produce a threshold depolarization. Small because they are less than that needed for threshold in the case of the depolarizing variety. Local means they only spread a few mm on the membrane and decline in intensity with increased distance from the point of the stimulus. The depolarizations are called EPSPs, excitatory post-synaptic potentials, because they tend to lead to an action potential which excites or turns the post-synaptic neuron on. Hyperpolarizations are called IPSPs, inhibitory post-synaptic potentials, because they tend to inhibit an action potential and thus turn the neuron off.

Summation - the EPSPs and IPSPs will add together to produce a net depolarization (or hyperpolarization).

Temporal summation- this is analogous to the frequency (wave, tetany) summation discussed for muscle. Many EPSPs occurring in a short period of time (e.g. with high frequency) can summate to produce threshold depolarization. This occurs when high intensity stimulus results in a high frequency of EPSPs.

Spatial summation - this is analogous to quantal summation in a muscle. It means that there are many stimuli occurring simultaneously. Their depolarizations spread and overlap and can build on one another to sum and produce threshold depolarization.

Inhibition - When the brain causes an IPSP in advance of a reflex pathway being stimulated, it reduces the likelihood of the reflex occurring by increasing the depolarization required. The pathway can still work, but only with more than the usual number or degree of stimulation. We inhibit reflexes when allowing ourselves to be given an injection or blood test for instance.

Facilitation - When the brain causes an EPSP in advance of a reflex pathway being stimulated, it makes the reflex more likely to occur, requiring less additional stimulation. When we anticipate a stimulus we often facilitate the reflex.

Learned Reflexes - Many athletic and other routine activities involve learned reflexes. These are reflex pathways facilitated by the brain. We learn the pathways by performing them over and over again and they become facilitated. This is how we can perfect our athletic performance, but only if we learn and practice them correctly. It is difficult to "unlearn" improper techniques once they are established reflexes. Like "riding a bike" they may stay with you for your entire life!

Post-tetanic potentiation - This occurs when we perform a rote task or other repetitive action. At first we may be clumsy at it, but after continuous use (post-tetanic) we become more efficient at it (potentiation). These actions may eventually become learned reflexes

The Action Potential

The trigger region of a neuron is the region where the voltage gated channels begin. When summation results in threshold depolarization in the trigger region of a neuron, an action potential is produced. There are both sodium and potassium channels. Each sodium channel has an activation gate and an inactivation gate, while potassium channels have only one gate. 

A) At the resting state the sodium activation gates are closed, sodium inactivation gates are open, and potassium gates are closed. Resting membrane potential is at around -70 mv inside the cell. 

B) Depolarizing phase: The action potential begins with the activation gates of the sodium channels opening, allowing Na+ ions to enter the cell and causing a sudden depolarization which leads to the spike of the action potential. Excess Na+ ions enter the cell causing reversal of potential becoming briefly more positive on the inside of the cell membrane.

C) Repolarizing phase: The sodium inactivation gates close and potassium gates open. This causes Na+ ions to stop entering the cell and  K+ ions  to leave the cell, causing repolarization. Until the membrane is repolarized it cannot be stimulated, called the absolute refractory period.

D) Excess potassium leaves the cell causing a brief hyperpolarization. Sodium activation gates close and potassium gates begin closing. The sodium-potassium pump begins to re-establish the resting membrane potential. During hyperpolarization the membrane can be stimulated but only with a greater than normal depolarization, the relative refractory period.

Action potentials are self-propagated, and once started the action potential progresses along the axon membrane. It is all-or-none, that is there are not different degrees of action potentials. You either have one or you don't.

HEART DISORDERS

1. Pump failure => Alters pressure (flow) =>alters oxygen carrying capacity.
   1. Renin release (Juxtaglomerular cells) Kidney
   2. Converts Angiotensinogen => Angiotensin I
   3. In lungs Angiotensin I Converted => Angiotensin II
   4. Angiotensin II = powerful vasoconstrictor (raises pressure, increases afterload)
      1. stimulates thirst
      2. stimulates adrenal cortex to release Aldosterone
         (Sodium retention, potassium loss)
      3. stimulates kidney directly to reabsorb Sodium
      4. releases ADH from Posterior Pituitary
2. Myocardial Infarction

    

   1. Myocardial Cells die from lack of Oxygen
   2. Adjacent vessels (collateral) dilate to compensate
   3. Intracellular Enzymes leak from dying cells (Necrosis)
      1. Creatine Kinase CK (Creatine Phosphokinase) 3 forms
         1. One isoenzyme = exclusively Heart (MB)
         2. CK-MB blood levels found 2-5 hrs, peak in 24 hrs
         3. Lactic Dehydrogenase found 6-10 hours after. points less clearly to infarction
      2. Serum glutamic oxaloacetic transaminase (SGOT)
         1. Found 6 hrs after infarction, peaks 24-48 hrs at 2 to 15 times normal,
         2. SGOT returns to normal after 3-4 days
   4. Myocardium weakens = Decreased CO & SV (severe - death)
   5. Infarct heal by fibrous repair
   6. Hypertrophy of undamaged myocardial cells
      1. Increased contractility to restore normal CO
      2. Improved by exercise program
   7. Prognosis
      1. 10% uncomplicated recovery
      2. 20% Suddenly fatal
      3. Rest MI not fatal immediately, 15% will die from related causes
3. Congenital heart disease (Affect oxygenation of blood)
   1. Septal defects
   2. Ductus arteriosus
   3. Valvular heart disease
      1. Stenosis = cusps, fibrotic & thickened, Sometimes fused, can not open
      2. Regurgitation = cusps, retracted, Do not close, blood moves backwards

• Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions):

• Alveoli
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Alveolar capillaries
  • Entering the alveolar capillaries
    • PO₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
    • PCO₂ = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 

• While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

• Leaving the alveolar capillaries
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
• • Entering the systemic capillaries
    • PO₂ = 100 mm Hg
    • PCO₂ = 40 mm Hg
  • Body cells (resting conditions)
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
• • Leaving the systemic capillaries
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Each hormone in the body is unique.  Each one is different in it's chemical composition, structure, and action.  With respect to their chemical structure, hormones may be classified into three groups: amines, proteins, and steroids.

 Amines- these simple hormones are  structural variation of the amino acid tyrosine.  This group includes thyroxine from the thyroid gland and epinephrine and norepinephrine from the adrenal medulla.

Proteins- these hormones are chains of amino acids.  Insulin from the pancreas, growth hormone from the anterior pituitary gland, and calcitonin from the thyroid gland are all proteins.  Short chains of amino acids are called peptides.  Antidiuretic hormone and oxytocin, synthesized by the hypothalamus, are peptide hormones.

Steroids- cholesterol is the precursor for the steroid hormones, which include cortisol and aldosterone from the adrenal cortex, estrogen and progesterone from the ovaries, and testosterone from the testes.

Ventilation simply means inhaling and exhaling of air from the atmospheric air into lungs and then exhaling it from the lung into the atmospheric air.
Air pressure gradient has to exist between two atmospheres to enable a gas to move from one atmosphere to an other.
 

During inspiration: the intrathoracic pressure has to be less than that of atmospheric pressure. This could be achieved by decreasing the intrathoracic pressure as follows:
 

Depending on Boyle`s law , the pressure of gas is inversely proportional to the volume of its container. So increasing the intrathoracic volume will decrease the intrathoracic pressure which will allow the atmospheric air to be inhaled (inspiration) . As decreasing the intrathoracic volume will increase the intrathoracic pressure and causes exhaling of air ( expiration)

So. Inspiration  could be actively achieved by the contraction of inspiratory muscles : diaphragm and intercostal muscles. While relaxation of the mentioned muscles will passively cause expiration.
 

Contraction of diaphragm will pull the diaphragm down the abdominal cavity ( will move inferiorly)  , and then increase the intrathoracic volume ( vertically)  . Contraction of external intercostal muscle will pull the ribs upward and forward which will additionally increase the intrathoracic volume ( transversely  , the net result will be increasing the intrathoracic volume and decreasing the intrathoracic pressure.
 

Relaxation of diaphragm will move it superiorly during expiration, the relaxation of external intercostal muscles will pull the ribs downward and backward , and the elastic lungs and chest wall will recoil. The net result is decreasing the intrathoracic volume and increasing intrathoracic pressure.
 

All of this occurs during quiet breathing. During forceful inspiration an accessory inspiratory muscle will be involved ( scaleni , sternocleidomastoid , and others) to increase negativity in the intrathoracic pressure more and more.
 

During forceful expiration the accessory expiratory muscles ( internal intercostal muscles and abdominal muscles ) will be involved to decrease the intrathoracic volume  more and more and then to increase  intrathoracic pressure more and more.

The pressure within the alveoli is called intralveolar  pressure . Between the two phases of respiration it is equal to the atmospheric pressure. It is decreased during inspiration ( about 1 cm H₂O ) and increased during expiration ( about +1 cm H₂O ) . This difference allow entering of 0.5 L of air into the lungs.

Intrapleural pressure is the pressure of thin fluid between the two pleural layers . It is a slight negative pressure. At the beginning of inspiration it is about -5 cm H2O and reachs -7.5 cm H₂O at the end or inspiration.

At the beginning of expiration the intrapleural pressure is -7.5 cm H₂O and reaches -5 cmH₂O at the end of expiration.
The difference between intralveolar pressure and intrapleural pressure is called transpulmonary pressure.

Factors , affecting ventilation :
 

Resistance : Gradual decreasing of the diameter of respiratory airway increase the resistance to air flow.
 

Compliance : means the ease , which the lungs expand.It depends on both the elastic forces of the lungs and the elastic forces , caused by the the surface tension of the fluid, lining the alveoli.
 

Surface tension: Molecules of water have tendency to attract each other on the surface of water adjacent to air. In alveoli the surface tension caused by the fluid in the inner surface of the alveoli  may cause collapse of alveoli . The surface tension is decreased by the surfactant .

Surfactant is a mixture of phospholipids , proteins and ion m produced by type II pneumocytes.

Immature newborns may suffer from respiratory distress syndrome , due to lack of surfactant which is produced during the last trimester of pregnancy.
 

The elastic fibers of the thoracic wall also participate in lung compliance.