Functional Divisions of the Nervous System:

1) The Voluntary Nervous System - (ie. somatic division) control of willful control of effectors (skeletal muscles) and conscious perception. Mediates voluntary reflexes.

2) The Autonomic Nervous System - control of autonomic effectors - smooth muscles, cardiac muscle, glands. Responsible for "visceral" reflexes

• Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions):

• Alveoli
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Alveolar capillaries
  • Entering the alveolar capillaries
    • PO₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
    • PCO₂ = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 

• While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

• Leaving the alveolar capillaries
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
• • Entering the systemic capillaries
    • PO₂ = 100 mm Hg
    • PCO₂ = 40 mm Hg
  • Body cells (resting conditions)
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
• • Leaving the systemic capillaries
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Blood Pressure

Blood moves through the arteries, arterioles, and capillaries because of the force created by the contraction of the ventricles.

Blood pressure in the arteries.

The surge of blood that occurs at each contraction is transmitted through the elastic walls of the entire arterial system where it can be detected as the pulse. Even during the brief interval when the heart is relaxed — called diastole — there is still pressure in the arteries. When the heart contracts — called systole — the pressure increases.

Blood pressure is expressed as two numbers, e.g., 120/80.

Blood pressure in the capillaries

The pressure of arterial blood is largely dissipated when the blood enters the capillaries. Capillaries are tiny vessels with a diameter just about that of a red blood cell (7.5 µm). Although the diameter of a single capillary is quite small, the number of capillaries supplied by a single arteriole is so great that the total cross-sectional area available for the flow of blood is increased. Therefore, the pressure of the blood as it enters the capillaries decreases.

Blood pressure in the veins

When blood leaves the capillaries and enters the venules and veins, little pressure remains to force it along. Blood in the veins below the heart is helped back up to the heart by the muscle pump. This is simply the squeezing effect of contracting muscles on the veins running through them. One-way flow to the heart is achieved by valves within the veins

Exchanges Between Blood and Cells

With rare exceptions, our blood does not come into direct contact with the cells it nourishes. As blood enters the capillaries surrounding a tissue space, a large fraction of it is filtered into the tissue space. It is this interstitial or extracellular fluid (ECF) that brings to cells all of their requirements and takes away their products. The number and distribution of capillaries is such that probably no cell is ever farther away than 50 µm from a capillary.

When blood enters the arteriole end of a capillary, it is still under pressure produced by the contraction of the ventricle. As a result of this pressure, a substantial amount of water and some plasma proteins filter through the walls of the capillaries into the tissue space.

Thus fluid, called interstitial fluid, is simply blood plasma minus most of the proteins. (It has the same composition and is formed in the same way as the nephric filtrate in kidneys.)

Interstitial fluid bathes the cells in the tissue space and substances in it can enter the cells by diffusion or active transport. Substances, like carbon dioxide, can diffuse out of cells and into the interstitial fluid.

Near the venous end of a capillary, the blood pressure is greatly reduced .Here another force comes into play. Although the composition of interstitial fluid is similar to that of blood plasma, it contains a smaller concentration of proteins than plasma and thus a somewhat greater concentration of water. This difference sets up an osmotic pressure. Although the osmotic pressure is small, it is greater than the blood pressure at the venous end of the capillary. Consequently, the fluid reenters the capillary here.

Control of the Capillary Beds

An adult human has been estimated to have some 60,000 miles of capillaries with a total surface area of some 800–1000 m². The total volume of this system is roughly 5 liters, the same as the total volume of blood. However, if the heart and major vessels are to be kept filled, all the capillaries cannot be filled at once. So a continual redirection of blood from organ to organ takes place in response to the changing needs of the body. During vigorous exercise, for example, capillary beds in the skeletal muscles open at the expense of those in the viscera. The reverse occurs after a heavy meal.

The walls of arterioles are encased in smooth muscle. Constriction of arterioles decreases blood flow into the capillary beds they supply while dilation has the opposite effect. In time of danger or other stress, for example, the arterioles supplying the skeletal muscles will be dilated while the bore of those supplying the digestive organs will decrease. These actions are carried out by

• the autonomic nervous system.
• local controls in the capillary beds

Reflexes

A reflex is a direct connection between stimulus and response, which does not require conscious thought. There are voluntary and involuntary reflexes.

The Stretch Reflex:

The stretch reflex in its simplest form involves only 2 neurons, and is therefore sometimes called a 2-neuron reflex. The two neurons are a sensory and a motor neuron. The sensory neuron is stimulated by stretch (extension) of a muscle. Stretch of a muscle normally happens when its antagonist contracts, or artificially when its tendon is stretched, as in the knee jerk reflex. Muscles contain receptors called muscle spindles. These receptors respond to the muscles's stretch. They send stimuli back to the spinal cord through a sensory neuron which connects directly to a motor neuron serving the same muscle. This causes the muscle to contract, reversing the stretch. The stretch reflex is important in helping to coordinate normal movements in which antagonistic muscles are contracted and relaxed in sequence, and in keeping the muscle from overstretching.

Since at the time of the muscle stretch its antagonist was contracting, in order to avoid damage it must be inhibited or tuned off in the reflex. So an additional connection through an interneuron sends an inhibitory pathway to the antagonist of the stretched muscle - this is called reciprocal inhibition.

The Deep Tendon Reflex:

Tendon receptors respond to the contraction of a muscle. Their function, like that of stretch reflexes, is the coordination of muscles and body movements. The deep tendon reflex involves sensory neurons, interneurons, and motor neurons. The response reverses the original stimulus therefore causing relaxation of the muscle stimulated. In order to facilitate that the reflex sends excitatory stimuli to the antagonists causing them to contract - reciprocal activation.

The stretch and tendon reflexes complement one another. When one muscle is stretching and stimulating the stretch reflex, its antagonist is contracting and stimulating the tendon reflex. The two reflexes cause the same responses thus enhancing one another.

The Crossed Extensor Reflex -

The crossed extensor reflex is just a withdrawal reflex on one side with the addition of inhibitory pathways needed to maintain balance and coordination. For example, you step on a nail with your right foot as you are walking along. This will initiate a withdrawal of your right leg. Since your quadriceps muscles, the extensors, were contracting to place your foot forward, they will now be inhibited and the flexors, the hamstrings will now be excited on your right leg. But in order to maintain your balance and not fall down your left leg, which was flexing, will now be extended to plant your left foot (e.g. crossed extensor). So on the left leg the flexor muscles which were contracting will be inhibited, and the extensor muscles will be excited

Oxygen Uptake in the Lungs is Increased About 70X by Hemoglobin in the Red Cells

• In the lungs oxygen must enter the blood
• A small amount of oxygen dissolves directly in the serum, but 98.5% of the oxygen is carried by hemoglobin
• All of the hemoglobin is found within the red blood cells (RBCs or erythrocytes)
• The hemoglobin content of the blood is about 15 gm/deciliter (deciliter = 100 mL)
• Red cell count is about 5 million per microliter

Each Hemoglobin Can Bind Four O₂ Molecules (100% Saturation)

• Hemoglobin is a protein molecule with 4 protein sub-units (2 alphas and 2 betas)
  • Each of the 4 sub-units contains a heme group which gives the protein a red color
  • Each heme has an iron atom in the center which can bind an oxygen molecule (O2)
  • The 4 hemes in a hemoglobin can carry a maximum of 4 oxygen molecules
• When hemoglobin is saturated with oxygen it has a bright red color; as it loses oxygen it becomes bluish (cyanosis)

The Normal Blood Hematocrit is Just Below 50%

• Blood consists of cells suspended in serum
• More than 99% of the cells in the blood are red blood cells designed to carry oxygen
  • 25% of all the cells in the body are RBCs
• The volume percentage of cells in the blood is called the hematocrit
• Normal hematocrits are about 40% for women and 45% for men

At Sea Level the Partial Pressure of O₂ is High Enough to Give Nearly 100% Saturation of Hemoglobin

• As the partial pressure of oxygen in the alveoli increases the hemoglobin in the red cells passing through the lungs rises until the hemoglobin is 100% saturated with oxygen
  • At 100% saturation each hemoglobin carries 4 O₂ molecules
  • This is equal to 1.33 mL O₂ per gram of hemoglobin
• A person with 15 gm Hb/deciliter can carry:
  • Max O₂ carriage = 1.33 mL O₂/gm X 15 gm/deciliter = 20 mL O₂/deciliter
• A plot of % saturation vs pO2 gives an S-shaped "hemoglobin dissociation curve"
• At 100% saturation each hemoglobin binds 4 oxygen molecules

At High Altitudes Hemoglobin Saturation May be Well Below 100%

• At the alveolar pO₂ of 105 mm Hg at sea level the hemoglobin will be about 97% saturated, but the saturation will fall at high altitudes
• At 12,000 feet altitude alveolar pO₂ will be about 60 mm Hg and the hemoglobin will be 90% saturated
• At 29,000 feet (Mt. Everest) alveolar pO₂ is about 24 mm Hg and the hemoglobin will be only 42% saturated
• At very high altitudes most climbers must breath pure oxygen from tanks
• During acclimatization to high altitude the hematocrit can rise to about 60%- this increases the amount of oxygen that can be carried
• Hematocrits above 60% are not useful because the blood viscosity will increase to the point where it impairs circulation

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 .