Serum Lipids

• Total cholesterol is the sum of
  • HDL cholesterol
  • LDL cholesterol and
  • 20% of the triglyceride value
• Note that
  • high LDL values are bad, but
  • high HDL values are good.
• Using the various values, one can calculate a
  cardiac risk ratio = total cholesterol divided by HDL cholesterol
• A cardiac risk ratio greater than 7 is considered a warning.

Bleeding Disorders

A deficiency of a clotting factor can lead to uncontrolled bleeding.

The deficiency may arise because

• not enough of the factor is produced or
• a mutant version of the factor fails to perform properly.

Examples:

• von Willebrand disease (the most common)
• hemophilia A for factor 8 deficiency
• hemophilia B for factor 9 deficiency.
• hemophilia C for factor 11 deficiency

In some cases of von Willebrand disease, either a deficient level or a mutant version of the factor eliminates its protective effect on factor 8. The resulting low level of factor 8 mimics hemophilia A.

• 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.

Excitability ( Bathmotropism ) : Excitability means the ability of cardiac muscle to respond to signals. Here we are talking about contractile muscle cells that are excited by the excitatory conductive system and generate an action potential.

Cardiac action potential is similar to action potential in nerve and skeletal muscle tissue , with one difference , which is the presence of plateau phase . Plateau phase is unique for cardiac muscle cells .
The  resting membrane potential for cardiac muscle is about -80 mV.
When the cardiac muscle is stimulated an action potential is generated . The action potential in cardiac muscle is composed of four phases , which are :

1. Depolarization phase (Phase 0 ) :

A result of opening of sodium channels , which increase the permeability to sodium , which will lead to a rapid sodium influx into the cardiac muscle cell.

2. Repolarization : Repolarization in cardiac muscle is slow and triphasic :

a. Phase 1 (early partial repolarization ) : A small fast repolarization , results from potassium eflux and chloride influx.
b. Phase 2 ( Plateau ) : After the early partial depolarization , the membrane remains  depolarized , exhibiting a plateau , which is a unique phase for the cardiac muscle cell. Plateau is due to opening of slow calcium-sodium channels , delay closure of sodium channels , and to decreased potassium eflux.
c. Phase 3  ( Rapid repolarization) :  opening of potassium channels and rapid eflux of potassium.
d. Phase 4 ( Returning to resting level) in other words : The phase of complete repolarization. This due to the work of sodium-potassium pump.

Absolute refractory period:

Coincides wit phase 0,phase1 , and phase 2 . During this period , excitability of the heart is totally abolished . This prevents tetanization of the cardiac muscle and enables the heart to contract and  relax to be filled by blood ..

Relative refractory period : 

Coincides with the rapid repolarization and allows the excitability to be gradually recovered .
Excitation contraction relationship : Contraction of cardiac muscle starts after depolarization and continues about 1.5 time as long as the duration of the action potential and reaches its maximum at the end of the plateau. Relaxation of the muscle starts with the early partial repolarization.

Factors , affecting excitability of cardiac muscle:

I. Positive bathmotropic effect :

1. Sympathetic stimulation : It increase the heart , and thus reduces the duration of the action potentia; . This will shorten the duration of the absolute refractory period , and thus increase the excitability .
2.  Drugs : Catecholamines and  xanthines derivatives .
3. Mild hypoxia and mild ischemia
4. Mild hyperkalemia as it decreases the K+ efflux and opens excess Na+ channels .
5. Hypocalcemia

II. Negative bathmotropic effect :

1. Parasympathetic stimulation: The negative bathmotropic effect is limited to the atrial muscle excitability , because there is no parasympathetic innervation for the ventricles. Parasympathetic stimulation decreases the heart rate , and thus increases the duration of cardiac action potential and thus increases the duration of the absolute refractory period.
2. moderate to severe hypoxia
3. hyponatremia , hypercalcemia , and severe hyperkalemia.

Clinical Physiology : Extrasystole is a pathological situation , due to abnormal impulses , arising from ectopic focus .It is expressed as an abnormal systole that occur during the early diastole .
Extrasystole  is due to a rising of excitability above the normal , which usually occurs after the end of the relative refractory period ( read about staircase phenomenon of Treppe)

Hormones are carried by the blood throughout the entire body, yet they affect only certain cells.  The specific cells that respond to a given hormone have receptor sites for that hormone.  

This is sort of a lock and key mechanism.  If the key fits the lock, then the door will open.  If a hormone fits the receptor site, then there will be an effect.  If a hormone and a receptor site do not match, then there is no reaction.  All of the cells that have receptor sites for a given hormone make up the target tissue for that hormone.  In some cases, the target tissue is localized in a single gland or organ.  In other cases, the target tissue is diffuse and scattered throughout the body so that many areas are affected.  

Hormones bring about their characteristic effects on target cells by modifying cellular activity.  Cells in a target tissue have receptor sites for specific hormones.  Receptor sites may be located on the surface of the cell membrane or in the interior of the cell.

In general those protein hormones are unable to diffuse through the cell membrane and react with receptor sites on the surface of the cell.  The hormone receptor reaction on the cell membrane activates an enzyme within the membrane, called adenyl cyclase, which diffuses into the cytoplasm.  Within the cell, adenyl cyclase catalyzes or starts the process of removal of phosphates from ATP to produce cyclic adenosine monophosphate or c AMP.  This c AMP activates enzymes within the cytoplasm that alter or change the cellular activity.  The protein hormone, which reacts at the cell membrane, is called the first messenger.  c Amp that brings about the action attributed to the hormone is called the second messenger.  This type of action is relatively rapid because the precursors are already present and they just needed to be activated in some way.  

Heart sounds

Heart sounds are a result of beating heart and resultant blood flow . that could be detected by a stethoscope during auscultation . Auscultation is a part of physical examination that doctors have to practice them perfectly.
Before discussion the origin and nature of the heart sounds we have to distinguish between the heart sounds and hurt murmurs. Heart murmurs are pathological noises that results from abnormal blood flow in the heart or blood vessels.
Physiologically , blood flow has a laminar pattern , which means that blood flows in form of layers , where the central layer is the most rapid . Laminar blood flow could be turned into turbulent one .

Turbulent blood flow is a result of stenotic ( narrowed ) valves or blood vessels , insufficient valves , roughened vessels` wall or endocardium ,  and many diseases . The turbulent blood flow causes noisy murmurs inside or outside the heart.

Heart sounds ( especially first and second sounds ) are mainly a result of closure of the valves of the heart . While the third sound is a result of vibration of ventricular wall and the leaflets of the opened AV valves after rapid inflow of blood from the atria to ventricles . 

Third heart sound is physiologic in children but pathological in adults.

The four heart sound is a result of the atrial systole and vibration of the AV valves , due to blood rush during atrial systole . It is inaudible neither in adults nor in children . It is just detectable by the phonocardiogram .

Characteristic of heart sounds :

1. First heart sound  (S1 , lub ) : a soft and low pitch sound, caused by closure of AV valves.Usually has two components ( M1( mitral ) and T1 ( tricuspid ). Normally M1 preceads T1.

2. Second heart sound ( S2 , dub) : sharp and high pitch sound . caused by closure of semilunar valves. It also has two components A2 ( aortic) and P2 ( pulmonary) . A2 preceads P2.

3. Third heart sound (S3) : low pitched sound.

4. Fourth heart sound ( S4) very low pitched sound.

As we notice : the first three sounds are related to ventricular activity , while the fourth heart sound is related to atrial activity.
Closure of valves is not the direct cause for heart sounds , but sharp blocking of blood of backward returning of blood by the closing valve is the direct cause.