Events in Muscle Contraction - the sequence of events in crossbridge formation:

1) In response to Ca²⁺ release into the sarcoplasm, the troponin-tropomyosin complex removes its block from actin, and the myosin heads immediately bind to active sites.

2) The myosin heads then swivel, the Working Stroke, pulling the Z-lines closer together and shortening the sarcomeres. As this occurs the products of ATP hydrolysis, ADP and Pi, are released.

3) ATP is taken up by the myosin heads as the crossbridges detach. If ATP is unavailable at this point the crossbridges cannot detach and release. Such a condition occurs in rigor mortis, the tensing seen in muscles after death, and in extreme forms of contracture in which muscle metabolism can no longer provide ATP.

4) ATP is hydrolyzed and the energy transferred to the myosin heads as they cock and reset for the next stimulus.

Excitation-Contraction Coupling: the Neuromuscular Junction  

Each muscle cell is stimulated by a motor neuron axon. The point where the axon terminus contacts the sarcolemma is at a synapse called the neuromuscular junction. The terminus of the axon at the sarcolemma is called the motor end plate. The sarcolemma is polarized, in part due to the unequal distribution of ions due to the Sodium/Potassium Pump.

1) Impulse arrives at the motor end plate (axon terminus) causing  Ca²⁺ to enter the axon.

2) Ca²⁺ binds to ACh vesicles causing them to release the ACh (acetylcholine) into the synapse by exocytosis. 

3) ACH diffuses across the synapse to bind to receptors on the sarcolemma. Binding of ACH to the receptors opens chemically-gated ion channels causing Na⁺ to enter the cell producing depolarization.

4) When threshold depolarization occurs, a new impulse (action potential) is produced that will move along the sarcolemma. (This occurs because voltage-gated ion channels open as a result of the depolarization -

5) The sarcolemma repolarizes:

a) K⁺ leaves cell (potassium channels open as sodium channels close) returning positive ions to the outside of the sarcolemma. (More K⁺ actually leaves than necessary and the membrane is hyperpolarized briefly. This causes the relative refractory period) (b) Na⁺/K⁺ pump eventually restores resting ion distribution.  The  Na⁺/K⁺ pump is very slow compared to the movement of ions through the ion gates. But a muscle can be stimulated thousands of times before the ion distribution is substantially affected.

6) ACH broken down by ACH-E (a.k.a. ACHase, cholinesterase). This permits the receptors to respond to another stimulus. 

Excitation-Contraction Coupling:

1) The impulse (action potential) travels along the sarcolemma. At each point the voltaged-gated Na+ channels open to cause depolarization, and then the K+ channels open to produce repolarization.

2) The impulse enters the cell through the T-tublules, located at each Z-disk, and reach the sarcoplasmic reticulum (SR), stimulating it.

3) The SR releases Ca²⁺ into the sarcoplasm, triggering the muscle contraction as previously discussed. 

4) Ca²⁺ is pumped out of the sarcoplasm by the SR and another stimulus will be required to continue the muscle contraction.

The Posterior Lobe

The posterior lobe of the pituitary releases two hormones, both synthesized in the hypothalamus, into the circulation.

• Antidiuretic Hormone (ADH).
  ADH is a peptide of 9 amino acids. It is also known as arginine vasopressin. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood.
  • A deficiency of ADH
    • leads to excessive loss of urine, a condition known as diabetes  nsipidus.
• Oxytocin
  Oxytocin is a peptide of 9 amino acids. Its principal actions are:
  • stimulating contractions of the uterus at the time of birth
  • stimulating release of milk when the baby begins to suckle

Respiration involves several components:

Ventilation - the exchange of respiratory gases (O₂ and CO₂) between the atmosphere and the lungs. This involves gas pressures and muscle contractions.

External respiration - the exchange of gases between the lungs and the blood. This involves partial pressures of gases, diffusion, and the chemical reactions involved in transport of O₂and CO₂.

Internal respiration - the exchange of gases between the blood and the systemic tissues. This involves the same processes as external respiration.

Cellular respiration - the includes the metabolic pathways which utilize oxygen and produce carbon dioxide, which will not be included in this unit.

Ventilation is composed of two parts: inspiration and expiration. Each of these can be described as being either quiet, the process at rest, or forced, the process when active such as when exercising.

Quiet inspiration:

The diaphragm contracts, this causes an increase in volume of the thorax and the lungs, which causes a decrease in pressure of the thorax and lungs, which causes air to enter the lungs, moving down its pressure gradient. Air moves into the lungs to fill the partial vacuum created by the increase in volume.

Forced inspiration:

Other muscles aid in the increase in thoracic and lung volumes.

The scalenes - pull up on the first and second ribs.

The sternocleidomastoid muscles pull up on the clavicle and sternum.

The pectoralis minor pulls forward on the ribs.

The external intercostals are especially important because they spread the ribs apart, thus increasing thoracic volume. It's these muscles whose contraction produces the "costal breathing" during rapid respirations.

Quiet expiration:

The diaphragm relaxes. The elasticity of the muscle tissue and of the lung stroma causes recoil which returns the lungs to their volume before inspiration. The reduced volume causes the pressure in the lungs to increase thus causing air to leave the lungs due to the pressure gradient.

Forced Expiration:

The following muscles aid in reducing the volume of the thorax and lungs:

The internal intercostals - these compress the ribs together

The abdominus rectus and abdominal obliques: internal obliques, external obliques- these muscles push the diaphragm up by compressing the abdomen.

Respiratory output is determined by the minute volume, calculated by multiplying the respiratory rate time the tidal volume.

Minute Volume = Rate (breaths per minute) X Tidal Volume (ml/breath)

Rate of respiration at rest varies from about 12 to 15 . Tidal volume averages 500 ml Assuming a rate of 12 breaths per minute and a tidal volume of 500, the restful minute volume is 6000 ml. Rates can, with strenuous exercise, increase to 30 to 40 and volumes can increase to around half the vital capacity.

Not all of this air ventilates the alveoli, even under maximal conditions. The conducting zone volume is about 150 ml and of each breath this amount does not extend into the respiratory zone. The Alveolar Ventilation Rate, AVR, is the volume per minute ventilating the alveoli and is calculated by multiplying the rate times the (tidal volume-less the conducting zone volume).

AVR = Rate X (Tidal Volume - 150 ml)

For a calculation using the same restful rate and volume as above this yields 4200 ml.

Since each breath sacrifices 150 ml to the conducting zone, more alveolar ventilation occurs when the volume is increased rather than the rate.

During inspiration the pressure inside the lungs (the intrapulmonary pressure) decreases to -1 to -3 mmHg compared to the atmosphere. The variation is related to the forcefulness and depth of inspiration. During expiration the intrapulmonary pressure increases to +1 to +3 mmHg compared to the atmosphere. The pressure oscillates around zero or atmospheric pressure.

The intrapleural pressure is always negative compared to the atmosphere. This is necessary in order to exert a pulling action on the lungs. The pressure varies from about -4 mmHg at the end of expiration, to -8 mmHg and the end of inspiration.

The tendency of the lungs to expand, called compliance or distensibility, is due to the pulling action exerted by the pleural membranes. Expansion is also facilitated by the action of surfactant in preventing the collapse of the alveoli.

The opposite tendency is called elasticity or recoil, and is the process by which the lungs return to their original or resting volume. Recoil is due to the elastic stroma of the lungs and the series elastic elements of the respiratory muscles, particularly the diaphragm.

Neurons :

Types of neurons based on structure:

a multipolar neuron because it has many poles or processes, the dendrites and the axon. Multipolar neurons are found as motor neurons and interneurons. There are also bipolar neurons with two processes, a dendrite and an axon, and unipolar neurons, which have only one process, classified as an axon.. Unipolar neurons are found as most of the body's sensory neurons. Their dendrites are the exposed branches connected to receptors, the axon carries the action potential in to the central nervous system.

Types of neurons based on function:

• motor neurons - these carry a message to a muscle, gland, or other effector. They are said to be efferent, i.e. they carry the message away from the central nervous system.
• sensory neurons - these carry a message in to the CNS. They are afferent, i.e. going toward the brain or spinal cord.
• interneuron (ie. association neuron, connecting neuron) - these neurons connect one neuron with another. For example in many reflexes interneurons connect the sensory neurons with the motor neurons.

Physiology - science that describes how organisms FUNCTION and survive in continually changing environments  

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 .