Clinical Physiology 

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) .

Bile contains:

• bile acids. These amphiphilic steroids emulsify ingested fat. The hydrophobic portion of the steroid dissolves in the fat while the negatively-charged side chain interacts with water molecules. The mutual repulsion of these negatively-charged droplets keeps them from coalescing. Thus large globules of fat (liquid at body temperature) are emulsified into tiny droplets (about 1 µm in diameter) that can be more easily digested and absorbed.

• bile pigments. These are the products of the breakdown of hemoglobin removed by the liver from old red blood cells. The brownish color of the bile pigments imparts the characteristic brown color of the feces.

The Lymphatic System

Functions of the lymphatic system:

1) to maintain the pressure and volume of the extracellular fluid by returning excess water and dissolved substances from the interstitial fluid to the circulation.

2) lymph nodes and other lymphoid tissues are the site of clonal production of immunocompetent  lymphocytes and macrophages in the specific immune response.
 

Filtration forces water and dissolved substances from the capillaries into the interstitial fluid. Not all of this water is returned to the blood by osmosis, and excess fluid is picked up by lymph capillaries to become lymph. From lymph capillaries fluid flows into lymph veins (lymphatic vessels) which virtually parallel the circulatory veins and are structurally very similar to them, including the presence of semilunar valves.

The lymphatic veins flow into one of two lymph ducts. The right lymph duct drains the right arm, shoulder area, and the right side of the head and neck. The left lymph duct, or thoracic duct, drains everything else, including the legs, GI tract and other abdominal organs, thoracic organs, and the left side of the head and neck and left arm and shoulder.

These ducts then drain into the subclavian veins on each side where they join the internal jugular veins to form the brachiocephalic veins.

Lymph nodes lie along the lymph veins successively filtering lymph. Afferent lymph veins enter each node, efferent veins lead to the next node becoming afferent veins upon reaching it.

Lymphokinetic motion (flow of the lymph) due to:

1) Lymph flows down the pressure gradient.

2) Muscular and respiratory pumps push lymph forward due to function of the semilunar valves.

Other lymphoid tissue: 

        1. Lymph nodes: Lymph nodes are small encapsulated organs located along the pathway of lymphatic vessels. They vary from about 1 mm to 1 to 2 cm in diameter and are widely distributed throughout the body, with large concentrations occurring in the areas of convergence of lymph vessels. They serve as filters through which lymph percolates on its way to the blood. Antigen-activated lymphocytes differentiate and proliferate by cloning in the lymph nodes. 

        2. Diffuse Lymphatic Tissue and Lymphatic nodules: The alimentary canal, respiratory passages, and genitourinary tract are guarded by accumulations of lymphatic tissue that are not enclosed by a capsule (i.e. they are diffuse) and are found in  connective tissue beneath the epithelial mucosa. These cells intercept foreign antigens and then travel to lymph nodes to undergo differentiation and proliferation. Local concentrations of lymphocytes in these systems and other areas are called lymphatic nodules. In general these are single and random but are more concentrated in the GI tract in the ileum, appendix, cecum, and tonsils. These are collectively called the Gut Associated Lymphatic Tissue (GALT). MALT (Mucosa Associated Lymphatic Tissue) includes these plus the diffuse lymph tissue in the respiratory tract. 

        3. The thymus:   The thymus is where immature lymphocytes differentiate into T-lymphocytes. The thymus is fully formed and functional at birth. Characteristic features of thymic structure persist until about puberty, when lymphocyte processing and proliferation are dramatically reduced and eventually eliminated and the thymic tissue is largely replaced by adipose tissue. The lymphocytes released by the thymus are carried to lymph nodes, spleen, and other lymphatic tissue where they form colonies. These colonies form the basis of T-lymphocyte proliferation in the specific immune response. T-lymphocytes survive for long periods and recirculate through lymphatic tissues.

        The transformation of primitive or immature lymphocytes into T-lymphocytes and their proliferation in the lymph nodes is promoted by a thymic hormone called thymosin.  Ocassionally the thymus persists and may become cancerous after puberty and and the continued secretion of thymosin and the production of abnormal T-cells may contribute to some autoimmune disorders.  Conversely, lack of thymosin may also allow inadequate immunologic surveillance and thymosin has been used experimentally to stimulate T-lymphocyte proliferation to fight lymphoma and other cancers. 

        4. The spleen: The spleen filters the blood and reacts immunologically to blood-borne antigens. This is both a morphologic (physical) and physiologic process. In addition to large numbers of lymphocytes the spleen contains specialized vascular spaces, a meshwork of reticular cells and fibers, and a rich supply of macrophages which monitor the blood.  Connective tissue forms a capsule and trabeculae which contain myofibroblasts, which are contractile.  The human spleen holds relatively little blood compared to other mammals, but it has the capacity for contraction to release this blood into the circulation during anoxic stress. White pulp in the spleen contains lymphocytes and is equivalent to other lymph tissue,  while red pulp contains large numbers of red blood cells that it filters and degrades.

    The spleen functions in both immune and hematopoietic systems. Immune functions include: proliferation of lymphocytes, production of antibodies, removal of antigens from the blood. Hematopoietic functions include: formation of blood cells during fetal life, removal and destruction of aged, damaged and abnormal red cells and platelets, retrieval of iron from hemoglobin degradation, storage of red blood cells.

Hemostasis - the  stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:

1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.

2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.

3) Formation of the Blood Clot:

A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.

B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.

C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.

The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.

Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.

Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.

Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are  VIII, IX, and XI.

Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage

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.

• There Are 12 Pairs of Cranial Nerves

• The 12 pairs of cranial nerves emerge mainly from the ventral surface of the brain
• Most attach to the medulla, pons or midbrain
• They leave the brain through various fissures and foramina of the skull

• Nerve	Name	Sensory	Motor	Autonomic Parasympathetic
  I	Olfactory	Smell
  II	Optic	Vision
  III	Oculomotor	Proprioception	4 Extrinsic eye muscles	Pupil constriction Accomodation Focusing
  IV	Trochlear	Proprioception	1 Extrinsic eye muscle (Sup.oblique)
  V	Trigeminal	Somatic senses (Face, tongue)	Chewing
  VI	Abducens	Proprioception	1 Extrinsic eye muscle (Lat. rectus)
  VII	Facial	Taste Proprioception	Muscles of facial expression	Salivary glands Tear glands
  VIII	Auditory (Vestibulocochlear)	Hearing, Balance
  IX	Glossopharyngeal	Taste Blood gases	Swallowing Gagging	Salivary glands
  X	Vagus	Blood pressure Blood gases  Taste	Speech Swallowing Gagging	Many visceral organs (heart, gut, lungs)
  XI	Spinal acessory	Proprioception	Neck muscles: Sternocleidomastoid Trapezius
  XII	Hypoglossal	Proprioception	Tongue muscles Speech

   

• Many of the functions that make us distinctly human are controlled by cranial nerves: special senses, facial expression, speech.

• Cranial Nerves Contain Sensory, Motor and Parasympathetic Fibers