Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.

When blood vessels are damaged, fibrils of collagen are exposed.

• von Willebrand factor links the collagen to platelets forming a plug of platelets there.
• The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
• (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)

ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.

Gonadotropin-releasing hormone (GnRH)

GnRH is a peptide of 10 amino acids. Its secretion at the onset of puberty triggers sexual development.

Primary Effects

FSH and LH Relaese

Secondary Effects

Increases estrogen and progesterone (in females)

testosterone Relaese (in males)

Growth hormone-releasing hormone (GHRH)

GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44.  GHRH stimulates cells in the anterior lobe of the pituitary to secrete growth hormone (GH).

Corticotropin-releasing hormone (CRH)

CRH is a peptide of 41 amino acids. Its acts on cells in the anterior lobe of the pituitary to release adrenocorticotropic hormone (ACTH) CRH is also synthesized by the placenta and seems to determine the duration of pregnancy.  It may also play a role in keeping the T cells of the mother from mounting an immune attack against the fetus

Somatostatin

Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to

• inhibit the release of growth hormone (GH)
• inhibit the release of thyroid-stimulating hormone (TSH)

Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

Antidiuretic hormone (ADH) and Oxytocin

These peptides are released from the posterior lobe of the pituitary

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)

CNS PROTECTION

- Bones of the Skull       Frontal, Temporal, Parietal, Sphenoid, Occipital

- Cranial Meninges         Dura mater, Arachnoid Space, Pia mater

- Cerebrospinal Fluid

Secreted by Chroid Plexi in Ventricles

Circulation through ventricles and central canal

Lateral and Median apertures from the 4th ventricle into the subarachnoid space

Arachnoid villi of the superior sagittal sinus return CSF to the venous circulation

Hydrocephalic Condition, blockage of the mesencephalic aqueduct, backup of CSF, Insertion of a shunt to drain the excess CSF

The cell membrane is called the sarcolemma. This membrane is structured to receive and conduct stimuli. The sarcoplasm of the cell is filled with contractile myofibrils and this results in the nuclei and other organelles being relegated to the edge of the cell.

Myofibrils are contractile units within the cell which consist of a regular array of protein myofilaments. Each myofilament runs longitudinally with respect to the muscle fiber. There are two types: the thick bands and the thin bands. Thick bands are made of multiple molecules of a protein called myosin. The thin bands are made of multiple molecules of a protein called actin. The thin actin bands are attached to a Z-line or Z-disk of an elastic protein called titin. The titin protein also extends into the myofibril anchoring the other bands in position. From each Z-line to the next is a unit called the 

    The sarcomere is the smallest contractile unit in the myofibril. Sarcomeres contract because the Z-lines move closer together. As the sarcomeres contract the myofibrils contract. As the myofibrils contract the muscle cell contracts. And as the cells contract the entire muscle contracts.

The arrangement of the thick myosin filaments across the myofibrils and the cell causes them to refract light and produce a dark band known as the A Band. In between the A bands is a light area where there are no thick myofilaments, only thin actin filaments. These are called the I Bands. The dark bands are the striations seen with the light microscope.

Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .

To understand the pathophysiology  of the heart failure ,  lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume

Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload    (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .

Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .

Contractility : Reducing the power of contraction such as in  myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .

Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.

Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility  . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff  .

The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .