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.

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.
 

Cell, or Plasma, membrane

• Structure - 2 primary building blocks include

protein (about 60% of the membrane) and lipid, or

fat (about 40% of the membrane).

The primary lipid is called phospholipids, and molecules of phospholipid form a 'phospholipid bilayer' (two layers of phospholipid molecules). This bilayer forms because the two 'ends' of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):

• Functions include:
  • supporting and retaining the cytoplasm
  • being a selective barrier .
  • transport
  • communication (via receptors)

Contractility : Means ability of cardiac muscle to convert electrical energy of action potential into mechanical energy ( work).
The excitation- contraction coupling of cardiac muscle is similar to that of skeletal muscle , except the lack of motor nerve stimulation. 

Cardiac muscle is a self-excited muscle , but the principles of contraction are the same . There are many rules that control the contractility of the cardiac muscles, which are:

1. All or none rule: due to the syncytial nature of the cardiac muscle.There are atrial syncytium and ventricular syncytium . This rule makes the heart an efficient pump.

2. Staircase phenomenon : means gradual increase in muscle contraction following rapidly repeated stimulation..

3. Starling`s law of the heart: The greater the initial length of cardiac muscle fiber , the greater the force of contraction. The initial length is determined by the degree of diastolic filling .The pericardium prevents overstretching of heart , and allows optimal increase in diastolic volume.

Thankful to this law , the heart is able to pump any amount of blood that it receives. But overstretching of cardiac muscle fibers may cause heart failure.

Factors affecting  contractility ( inotropism)

I. Positive inotropic factors:

1. sympathetic stimulation: by increasing the permeability of sarcolemma to calcium.
2. moderate increase in temperature . This due to increase metabolism to increase ATP , decrease viscosity of myocardial structures, and increasing calcium influx.
3. Catecholamines , thyroid hormone, and glucagon hormones.
4. mild alkalosis
5. digitalis
6. Xanthines ( caffeine and theophylline )

II. Negative inotropic factors:

1. Parasympathetic stimulation : ( limited to atrial contraction)
2. Acidosis
3. Severe alkalosis
4. excessive warming and cooling .
5. Drugs ;like : Quinidine , Procainamide , and barbiturates .
6. Diphtheria and typhoid toxins.

Graded Contractions and Muscle Metabolism

The muscle twitch is a single response to a single stimulus. Muscle twitches vary in length according to the type of muscle cells involved. .

Fast twitch muscles such as those which move the eyeball have twitches which reach maximum contraction in 3 to 5 ms (milliseconds).  [superior eye] and [lateral eye] These muscles were mentioned earlier as also having small numbers of cells in their motor units for precise control.

The cells in slow twitch muscles like the postural muscles (e.g. back muscles, soleus) have twitches which reach maximum tension in 40 ms or so.

 The muscles which exhibit most of our body movements have intermediate twitch lengths of 10 to 20 ms.

The latent period, the period of a few ms encompassing the chemical and physical events preceding actual contraction.

This is not the same as the absolute refractory period, the even briefer period when the sarcolemma is depolarized and cannot be stimulated. The relative refractory period occurs after this when the sarcolemma is briefly hyperpolarized and requires a greater than normal stimulus

Following the latent period is the contraction phase in which the shortening of the sarcomeres and cells occurs. Then comes the relaxation phase, a longer period because it is passive, the result of recoil due to the series elastic elements of the muscle.

We do not use the muscle twitch as part of our normal muscle responses. Instead we use graded contractions, contractions of whole muscles which can vary in terms of their strength and degree of contraction. In fact, even relaxed muscles are constantly being stimulated to produce muscle tone, the minimal graded contraction possible.

Muscles exhibit graded contractions in two ways:

1) Quantal Summation or Recruitment - this refers to increasing the number of cells contracting. This is done experimentally by increasing the voltage used to stimulate a muscle, thus reaching the thresholds of more and more cells. In the human body quantal summation is accomplished by the nervous system, stimulating increasing numbers of cells or motor units to increase the force of contraction.

2) Wave Summation ( frequency summation) and Tetanization- this results from stimulating a muscle cell before it has relaxed from a previous stimulus. This is possible because the contraction and relaxation phases are much longer than the refractory period. This causes the contractions to build on one another producing a wave pattern or, if the stimuli are high frequency, a sustained contraction called tetany or tetanus. (The term tetanus is also used for an illness caused by a bacterial toxin which causes contracture of the skeletal muscles.) This form of tetanus is perfectly normal and in fact is the way you maintain a sustained contraction.

Treppe is not a way muscles exhibit graded contractions. It is a warmup phenomenon in which when muscle cells are initially stimulated when cold, they will exhibit gradually increasing responses until they have warmed up. The phenomenon is due to the increasing efficiency of the ion gates as they are repeatedly stimulated. Treppe can be differentiated from quantal summation because the strength of stimulus remains the same in treppe, but increases in quantal summation

Length-Tension Relationship: Another way in which the tension of a muscle can vary is due to the length-tension relationship. This relationship expresses the characteristic that within about 10% the resting length of the muscle, the tension the muscle exerts is maximum. At lengths above or below this optimum length the tension decreases.

Plasma:  is the straw-colored liquid in which the blood cells are suspended.

Plasma transports materials needed by cells and materials that must be removed from cells:

• various ions (Na⁺, Ca²⁺, HCO₃⁻, etc.
• glucose and traces of other sugars
• amino acids
• other organic acids
• cholesterol and other lipids
• hormones
• urea and other wastes

Most of these materials are in transit from a place where they are added to the blood

• exchange organs like the intestine
• depots of materials like the liver

to places where they will be removed from the blood.

• every cell
• exchange organs like the kidney, and skin.