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.

Respiration occurs in three steps :
1- Mechanical ventilation : inhaling and exhaling of air between lungs and atmosphere.
2- Gas exchange : between pulmonary alveoli and pulmonary capillaries.
3- Transport of gases from the lung to the peripheral tissues , and from the peripheral tissues back to blood .
These steps are well regulated by neural and chemical regulation.

Respiratory tract is subdivided into upper and lower respiratory tract. The upper respiratory tract involves , nose , oropharynx and nasopharynx , while the lower respiratory tract involves larynx , trachea , bronchi ,and lungs .

Nose fulfills three important functions which are :

1. warming of inhaled air .

b. filtration of air .

c. humidification of air .

Pharynx is a muscular tube , which forms a passageway for air and food .During swallowing the epiglottis closes the larynx and the bolus of food falls in the esophagus .

Larynx is a respiratory organ that connects pharynx with trachea . It is composed of many cartilages and muscles and

vocal cords . Its role in respiration is limited to being a conductive passageway for air .

Trachea is a tube composed of C shaped cartilage rings from anterior side, and of muscle (trachealis muscle ) from its posterior side.The rings prevent trachea from collapsing during the inspiration. 

From  the trachea the bronchi are branched into right and left bronchus ( primary bronchi) , which enter the lung .Then they repeatedly branch into secondary and tertiary bronchi and then into terminal and respiratory broncholes.There are about 23 branching levels from the right and left bronchi to the respiratory bronchioles  , the first upper  17 branching are considered as a part of the conductive zones , while the lower 6 are considered to be respiratory zone. 

The cartilaginous component decreases gradually from the trachea to the bronchioles  . Bronchioles are totally composed of smooth muscles ( no cartilage) . With each branching the diameter of bronchi get smaller , the smallest diameter of respiratory passageways is that of respiratory bronchiole. 

Lungs are evolved by pleura . Pleura is composed of two layers : visceral and parietal .
Between the two layers of pleura , there is a pleural cavity , filled with a fluid that decrease the friction between the visceral and parietal pleura.
 

Respiratory muscles : There are two group of respiratory muscles:

1. Inspiratory muscles : diaphragm and external intercostal muscle ( contract during quiet breathing ) , and accessory inspiratory muscles : scaleni , sternocleidomastoid , internal pectoral muscle , and others( contract during forceful inspiration).
 

2. Expiratory muscles : internal intercostal muscles , and abdominal muscles ( contract during forceful expiration)

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

White Blood Cells (leukocytes)

White blood cells

• are much less numerous than red (the ratio between the two is around 1:700),
• have nuclei,
• participate in protecting the body from infection,
• consist of lymphocytes and monocytes with relatively clear cytoplasm, and three types of granulocytes, whose cytoplasm is filled with granules.

Lymphocytes: There are several kinds of lymphocytes, each with different functions to perform , 25% of wbc The most common types of lymphocytes are

• B lymphocytes ("B cells"). These are responsible for making antibodies.
• T lymphocytes ("T cells"). There are several subsets of these:
  • inflammatory T cells that recruit macrophages and neutrophils to the site of infection or other tissue damage
  • cytotoxic T lymphocytes (CTLs) that kill virus-infected and, perhaps, tumor cells
  • helper T cells that enhance the production of antibodies by B cells

Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the bone marrow to the thymus where they mature. Both B cells and T cells also take up residence in lymph nodes, the spleen and other tissues where they

• encounter antigens;
• continue to divide by mitosis;
• mature into fully functional cells.

Monocytes : also originate in marrow, spend up to 20 days in the circulation, then travel to the tissues where they become macrophages. Macrophages are the most important phagocyte outside the circulation. Monocytes are about 9% of normal wbc count

Macrophages are large, phagocytic cells that engulf

• foreign material (antigens) that enter the body
• dead and dying cells of the body.

Neutrophils

The most abundant of the WBCs. about 65% of normal white count  These cells spend 8 to 10 days in the circulation making their way to sites of infection etc  Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis. They have two types of granules: the most numerous are specific granules which contain bactericidal agents such as lysozyme; the azurophilic granules are lysosomes containing peroxidase and other enzymes

Eosinophils : The number of eosinophils in the blood is normally quite low (0–450/µl). However, their numbers increase sharply in certain diseases, especially infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents of their granules on the invader.

Basophils : rare except during infections where these cells mediate inflammation by secreting histamine and heparan sulfate (related to the anticoagulant heparin). Histamine makes blood vessels permeable and heparin inhibits blood clotting. Basophils are functionally related to mast cells.  . The mediators released by basophils also play an important part in some allergic responses such as hay fever and an anaphylactic response to insect stings.

Thrombocytes (platelets):

Thrombocytes are cellular derivatives from megakaryocytes which contain factors responsible for the intrinsic clotting mechanism. They represent fragmented cells  which contain residual organelles including rough endoplasmic reticulum and Golgi apparati. They are only 2-microns in diameter, are seen in peripheral blood either singly or, often, in clusters, and have a lifespan of 10 days.

As the contents of the stomach become thoroughly liquefied, they pass into the duodenum, the first segment  of the small intestine. The duodenum is the first 10" of the small intestine

Two ducts enter the duodenum:

• one draining the gall bladder and hence the liver
• the other draining the exocrine portion of the pancreas.

From the intestinal mucosal cells, and from the liver and gallbladder. Secretions from the pancreas and bile from the gallbladder enter the duodenum through the hepatopancreatic ampulla and the sphincter of Oddi. These lie where the pancreatic duct and common bile duct join before entering the duodenum. The presence of fatty chyme in the duodenum causes release of the hormone CCK into the bloodstream. CCK is one of the enterogastrones and its main function, besides inhibiting the stomach, is to stimulate the release of enzymes by the pancreas, and the contraction of the gallbladder to release bile. It also stimulates the liver to produce bile. Consumption of excess fat results in excessive bile production by the liver, and this can lead to the formation of gallstones from precipitation of the bile salts. 

The acid in the chyme stimulates the release of secretin which causes the pancreas to release bicarbonate which neutralizes the acidity

An anti-diruetic is a substance that decreases urine volume, and ADH is the primary example of it within the body. ADH is a hormone secreted from the posterior pituitary gland in response to increased plasma osmolarity (i.e., increased ion concentration in the blood), which is generally due to an increased concentration of ions relative to the volume of plasma, or decreased plasma volume.

The increased plasma osmolarity is sensed by osmoreceptors in the hypothalamus, which will stimulate the posterior pituitary gland to release ADH. ADH will then act on the nephrons of the kidneys to cause a decrease in plasma osmolarity and an increase in urine osmolarity.

ADH increases the permeability to water of the distal convoluted tubule and collecting duct, which are normally impermeable to water. This effect causes increased water reabsorption and retention and decreases the volume of urine produced relative to its ion content.

After ADH acts on the nephron to decrease plasma osmolarity (and leads to increased blood volume) and increase urine osmolarity, the osmoreceptors in the hypothalamus will inactivate, and ADH secretion will end. Due to this response, ADH secretion is considered to be a form of negative feedback.