Remember the following principles before proceeding :
- Reabsorption occurs for most of substances that have been previously filterd .
- The direction of reabsorption is from the tubules to the peritubular capillaries
- All of transport mechanism are used here.
- Different morphology of the cells of different parts of the tubules contribute to reabsorption of different substances .
- There are two routes of reabsorption: Paracellular and transcellular : Paracellular reabsorption depends on the tightness of the tight junction which varies from regeon to region in the nephrons .Transcellular depends on presence of transporters ( carriers and channels for example).

1. Reabsorption of glucose , amino acids , and proteins :

Transport of glucose occurs in the proximal tubule . Cells of proximal tubules are similar to those of the intestinal mucosa as the apical membrane has brush border form to increase the surface area for reabsorption , the cells have plenty of mitochondria which inform us that high amount of energy is required for active transport , and the basolateral membrane of the cells contain sodium -potassium pumps , while the apical membrane contains a lot of carrier and channels .

The tight junction between the tubular cells of the proximal tubules are not that (tight) which allow paracellular transport.
Reabsorption of glucose starts by active transport of  Na by the pumps on the basolateral membrane . This will create Na gradient which will cause Na to pass the apical membrane down its concentration gradient . Glucose also passes the membrane up its concentration gradient using sodium -glucose symporter as a secondary active transport.

The concentration of glucose will be increased in the cell and this will enable the glucose to pass down concentration gradient to the interstitium by glucose uniporter . Glucose will then pass to the peritubular capillaries by simple bulk flow.

Remember: Glucose reabsorption occurs via transcellular route .
          Glucose transport has transport maximum . In normal situation there is no glucose in the urine , but in uncontrolled diabetes mellitus patients glucose level exceeds its transport maximum (390 mg/dl) and thus will appear in urine .
                   
                   
                   
2. Reabsorption of Amino acids : Use secondary active transport mechanism like glucose.

3. Reabsorption of proteins : 

Plasma proteins are not filtered in Bowman capsule but some proteins and peptides in blood may pass the filtration membrane and then reabsorbed . Some peptides are reabsorbed paracellulary , while the others bind to the apical membrane and then enter the cells by endocytosis , where they will degraded by peptidase enzymes to amino acids .

4. Reabsorption of sodium , water , and chloride:

65 % of sodium is reabsorbed in the proximal tubules , while 25% are reabsorbed in the thick ascending limb of loob of Henle , 9% in the distal and collecting tubules and collecting ducts .
90% of sodium reabsorption occurs independently from its plasma level (unregulated) , This is true for sodium reabsorbed in proximal tubule and loop of Henle , while the 9% that is reabsorbed in distal ,collecting tubules and collecting ducts is regulated by Aldosterone. 

In proximal tubules : 65% of sodium is reabsorbed . The initial step occurs by creating sodium gradient  by sodium-potassium pump on the basolateral membrane . then the sodium will pass from the lumen into the cells down concentration gradient by sodium -glucose symporter , sodium -phosphate symporter and by sodium- hydrogen antiporter and others                    
                   
After reabsorption of sodium , an electrical gradient will be created , then chloride is reabsorbed following the sodium  . Thus the major cation and anion leave the lumen to the the interstitium and thus the water follows by osmosis . 65% of water is reabsorbed in the proximal tubule.

Discending limb of loop of Henle is impermeable to electrolytes but avidly permeable to water . 10 % of water is reabsorbed in the discending thin limb of loob of Henle .

The thick ascending limb of loop of Henly is permeable to electrolytes , due to the presence of Na2ClK syporter . 25% of sodium is reabsorbed here .

In the distal and collecting tubules and the collecting ducts 9% of sodium is reabsorbed .this occurs under aldosterone control depending on sodium plasma level. 1% of sodium is excreted .

Water is not reabsorbed from distal tubule but 5-25% of water is reabsorbed in collecting tubules .

Conductivity :

 Means ability of cardiac muscle to propagate electrical impulses through the entire heart ( from one part of the heart to another)  by the excitatory -conductive system of the heart.
 
Excitatory conductive system of the heart involves:

1. Sinoatrial node ( SA node) : Here the initial impulses start and then conducted to the atria through  the anterior inter-atrial pathway ( to the left atrium) , to the atrial muscle mass through the gap junction, and to the Atrioventricular node ( AV node ) through anterior, middle , and posterior inter-nodal pathways.
The average conductive velocity in the atria is 1m/s.

2- AV node : The electrical impulses can not be conducted directly from the atria to the ventricles , because of the  fibrous skeleton , which is an electrical isolator , located between the atria and ventricles. So the only conductive way is the AV node . But there is a delay in the conduction occurs in the AV node .
This delay is due to:
- the smaller size of the nodal fiber.
- The less negative resting membrane potential
- fewer gap junctions.

There are three sites for delay:
- In the transitional fibers , that connect inter-nodal pathways with the AV node ( 0.03 ) .
- AV node itself ( 0.09 s) .
- In the penetrating portion of Bundle of Hiss ( 0.04 s)  .
This delay actually allows atria to empty blood in ventricles during the cardiac cycle before the beginning of ventricular contraction  , as it prevents the ventricles from the pathological high atrial rhythm.
The average velocity of conduction in the AV node is 0.02-0.05 m/s

3- Bundle of Hiss : A continuous with the AV node that passes to the ventricles through the inter-ventricular septum. It is subdivided into : Right and left bundle. The left bundle is also subdivided into two branches: anterior and posterior branches .

4- Purkinje`s fibers: large fibers with velocity of conduction 1.5-4 m/s.
the high velocity of these fibers is due to the abundant gap junctions , and to their nature as very large fibers as well.
The conduction from AV node is a one-way conduction . This prevents the re-entry of cardiac impulses from the ventricles to the atria.
Lastly: The conduction through the ventricular fibers has a velocity of 0.3-0.5 m/s.

Factors , affecting conductivity ( dromotropism)  :

I. Positive dromotropic factors :

1. Sympathetic stimulation : it accelerates conduction and decrease AV delay .
2. Mild warming
3. mild hyperkalemia
4. mild ischemia
5. alkalosis

II. Negative dromotropic factors :

1. Parasympathetic stimulation
2. severe warming
3. cooling
4. Severe hyperkalemia
5. hypokalemia
6. Severe ischemia
7. acidosis
8. digitalis drugs.

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.

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)

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.

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)