Diabetes and Glaucoma

Diabetes, Glaucoma and Homeostasis

Remember, the main function of our body systems provides a perfect environment for a cell to live.

Acidity, concentrations of electrolytes, removing wastes, 98.6 degrees F, food (glucose) , a perfect place to live forever.

Diabetics have trouble maintaining that environment. Insulin regulation and diet are important. The problem is the blood capillaries. The capillaries continue to gradually decline in their ability to maintain essential solute molecules to retrain blood volume. Regulating insulin doesn't stop the breakdown of capillaries.

Its like a movie in slow motion. How can a person with diabetes stop this slow degradation of the capillary single cell thick membrane? Research will continue to probe and test. Right now there isn't a cure.

Since the capillaries reach everywhere in our body where living cells reside there are numerous exchange points for providing fluid (water) that disappears from the blood only to return a short time later. How does this work in the  eye?

A capillary bed is an exchange point for maintaining a function for an organ, part of an organ, tissues, spaces inside a structure - anywhere fluid provides products the body uses and fluids.

A capillary has an arterial end (think high pressure) and a venous end (think lower pressure). In the eye what does a capillary bed provide that makes our vision operate well?

It provides water.(think incompressible) The water maintains the shape of the eye so the mechanics of vision can function. Its like a stream flowing along , at the same rate, year after year. 

In glaucoma, one end of the capillary bed is not functioning well. Blood pressure supplies the water to the interior of the eye and the venous end of the capillary bed is supposed to reabsorb exactly the same amount of water that enters the eye chamber from the arterial end of the capillary bed.

In a person suffering from glaucoma the above does not take place. There is an imbalance. More water is formed than water reabsorbed. Keep in mind this difference is very slow in developing. 

What is the reason why there may be a connection between a history of glaucoma and diabetes? The deterioration of the capillary membrane from, possibly (don't know for sure), diabetes. 

When the larger solute molecules leave the blood capillaries at the arterial end of the capillary bed the venous end has lost its ability to reabsorb all the water that was formed by osmosis. 

Since water is incompressible it will put increased pressure on the optic nerve over time. The sensitive retinal layer, in the rear of the eyeball, begins to fail from the increase of pressure. You will develop blindness if the buildup in pressure continues without detection. Total destruction of the retinal layer will render you blind. 

See an Ophthalmologist for an eye examination if you are diabetic or, if not diabetic, were screened and found to have intraocular pressure readings from a Tonometer exceeding 20. 

The treatment is easy and painless. One drop of a fluid to each eye each day will keep the buildup from happening.

What if a Concentration Gradient Doesn't Exist?

Active Transport and Concentration Gradients - Energy

In the nervous system and muscle system small particles with electrical charges use active transport carriers to recover the functioning capability of each body system.

Remember what the purpose of glucose is to a living cell? It provides a large molecule, glucose, that is broken up and acted upon in a cycle that produces usable chemical energy.

The energy produced is stored by the cells as ATP. It is in the form of a high energy bond associated with ATP. When a cell needs energy for one or more functions the ATP provides that energy.

There are two types on active transport mechanisms. One is associated with small particles like Sodium Ions (+), Chloride Ions (-), Potassium Ions (+), Hydrogen Ions (+) Calcium Ions (+) and a few more complex ions like NH4 (+), HCO3 (-) and Phosphate Ions (-). The other with larger protein molecules that I will post on tomorrow.

Example of a small particle active transport:

When a nerve is ready to receive an impulse that eventually reaches the brain for interpretation, it prepares by fixing its cell membrane to carry an electrical charge.

A nerve cell membrane has a large concentration of Sodium Ions (+) on the outside of the membrane and a large concentration of Potassium ions (+) on the inside of the cell membrane. 

The cell, when it has a larger concentration of positive ions on one side (outer membrane surface) and a lower concentration of positive ions on the inside of the membrane (both positive) the cell membrane is polarized (ready to create a electrical charge by depolarizing.}

Think of a nerve as a railroad track. On the track is a single railroad car. Wherever the railroad car is a depolarization is taking place. All the Sodium Ions are rushing into the cell through the selectively permeable membrane and all the Potassium Ions rush out of the same membrane. 

After the railroad car has passed over a section of track it begins the process of depolarization. The nerve cell calls upon its supply of ATP to provide energy to push the Sodium ions back out of the nerve cell against its concentration gradient. There are many more Sodium Ions out there even after a depolarization.

A small carrier molecule picks up a Sodium Ion, carries it to the external membrane surface and releases it.

Instead of wasting its return trip to pick up another Sodium Ion the carrier molecule picks up a Potassium Ion and returns (against its concentration gradient) it to the cell interior by active transport. Its like a two way pump that re-establishes the polarity across the nerve cell membrane.

All this activity needs energy to function. Once the nerve cell is depolarized it is ready to receive a new nerve impulse. 

In review, active transport uses energy to push a particle (ion) through a selectively permeable membrane against its concentration gradient.

The Importance of Large Molecules in Blood Vessels

Fluid Balance and the Role of Large Molecules

Water is a critical fluid in maintaining life. How does the circulatory system maintain its volume? What role does osmosis play in the circulatory retention of water?

First, just what is a solute particle? In the blood capillary the two major solute particles that are to large to pass through the selectively permeable membrane are albumins and globulins. They are found in the blood plasma. Problems begin when the number of albumins and globulins escape from the blood capillary.

Normally they are always present in the capillary and provide the high concentration of solute molecules that cause water, a solvent, to enter the blood capillary via osmosis.

This is very important. The circulatory system is the transportation system of our body. The volume of the circulatory system is critical for maintaining blood pressure and the prevention of circulatory collapse.

Therefore, again, osmosis is the movement of water from an area of low solute concentration to an area of high solute concentration through a selectively permeable membrane.

In this example, the importance of retaining the albumins and globulins in the blood capillaries is paramount. In the kidneys the functional unit is the glomerulus. It is here the blood, under pressure, loses (filters out ) almost everything that is considered a solute except for albumins, globulins and red blood cells. 

In diabetes the capillaries become inflamed (an "itis," attached to a medical term, is used to convey an inflammation of something) For instance, glomerulitis means an inflammation of the capillaries of the glomerulus.

When glomerular capillaries are inflamed spaces appear between the capillary cells that are now large enough for albumins, globulins and red blood cells to pass through into the interstitial fluid. Now we really have problems.

The capillaries of the circulatory system are unable to reconstitute the circulatory system with water that was lost during the initial filtration by the kidneys.

When the inflammation is treated the capillaries are again able to retain water by osmosis. This damage is the very serious for the diabetic. It occurs, even though a person has their insulin under control.

If you ever attended a "Walk for the Cure" event for Diabetes they have T- Shirts for participants. This is a little different.

I use this example to point in the direction of other solute particles, like ions and smaller molecules, that are selectively moved to create osmotic effects for water transport.

Above all else the integrity of the cells that make up a capillary must be maintained without leakage of the albumins, globulins and red blood cells for our body to function. This is a challenge for physicians treating diabetics.

The Traveling Man - Glucose

Glucose - A Molecule in Motion with a Purpose

Lets begin with its breakdown. It starts with a polysaccharide to a disaccharide to a monosaccharide (glucose). All of this begins in the mouth. Glucose is so important to you it gives excessive time to digest all the basic sugar components of nutrition you provide. 

Keep in mind, the pancreas is both an endocrine organ ( insulin and glucagon) and an exocrine organ (digestive enzymes for disaccharides, dipeptides and fats). Hormones are secreted directly into the circulatory system and are global( Reaches all cells supplied by blood capillaries). Enzymes work locally and enter  their workplace through a tube into the small intestine.

One very important principal is the concept of surface area. There is a direct correlation between an increase in the rate and quantity of absorption of digestion products and the increase in the surface area exposed to the end product glucose.

Surface area is one of the factors that scientists use to differentiate lower animals from higher animals like us. The increased surface area in our intestines (especially the small intestine) allows us to meet our energy demands efficiently and quickly. This is a big improvement over lesser creatures.

Once in its final stage of breakdown (the monosaccharide glucose) it is absorbed in the small worm-like villae that cover the inside of the small intestine. They really increase the surface area used for absorption.

Remember, it passes through the mosaic membrane of the cells (intracellular fluid compartment) that are in direct contact with the glucose in the small intestine. It now exits that membrane cell on the other side of the cell membrane into a fluid matrix called the interstitial fluid compartment of the extracellular fluid compartment. It travels through that compartment where it enters the intracellular fluid compartment of a cell layer that makes up blood capillary.

It leaves the cell that lines the blood capillary. In review, it goes from an intracellular compartment into the blood capillary fluid that makes up the other compartment of the extracellular fluid.

The blood, with the dissolved glucose in it is transported to all the cells that use glucose for energy.

Excess glucose that isn't used enters the kidneys where it is excreted into the urine. It is similar to water flowing over a dam. This occurs when something is amiss. Maybe insulin is not produced adequately and this excess is in addition to the glucose transported to the liver for storage as glycogen. It may be called back as glucose in emergencies.

The glucose that is still present in the blood, in very high amounts, even after flowing over the dam in the kidneys, is Diabetes. (The result of not facilitating the uptake of glucose that we described above)

This trip we just took is a one way trip. There is some glucose that is converted to a more complex molecule and stored in the liver. This more complex stored molecule breaks down in the liver, when called upon, to provide glucose when your blood sugar is low due to a number of factors.

I don't know about you but my feet are a little sore from walking with the glucose molecule on its trip. You should begin to realize now how complex your body has developed to accomplish all this without you really knowing that it is happening.

Negative and Positive Feedback Systems - Homeostasis

Concentration Gradients and Homeostasis

Time to backup and talk about feedback systems that keep the concentration of things your body needs to function normally.

Homeostasis is a state reached when your chemicals necessary for life are within their normal concentration range.

Wide swings in concentrations is not good. You don't feel good when "wide swings" occur. Do you feel good with high concentrations of glucose in your blood that persist? No.

A "Negative Feedback System" , when operating normally, prevents "wide swings" in the concentration of substances that are important to your body systems. One of these chemicals is a by-product of digestion.

If the body produces glucose for the metabolism necessary for life in all our living cells there is a feedback system ( this link is a series of excellent diagrams of negative and positive feed back systems) for glucose that turns off the production of glucose when it is no longer needed. It does this to prevent the concentration of glucose to reach levels in the blood that are dangerous. The swing upward (wide swing) of glucose is too great if the feedback system isn't working.

Lets look at a muscle cell. If its contracting it needs food (glucose) to manufacture energy for contraction to occur. When the period of contraction ends the need for glucose ends. To conserve glucose for another time a process takes place to remove the excess glucose from the blood and store it. The normal level of glucose is maintained. Insulin does this normally.

Think of a small stone thrown into a quiet pond. Little waves are produced. This is very similar to the small up and down swings in your glucose concentration if the feedback system is working well. This is homeostasis. 

The process is called a "Negative Feedback System." It prevents "wide swings" in the concentration of necessary chemicals, like glucose, from occurring.   It starts a system up to provide the necessary chemical (glucose) and shuts down the process when the need for (glucose) temporarily disappears. The body likes to save essential chemicals for a later time.

For a diabetic, the pancreas is not producing enough insulin to bring the concentration of glucose back to normal levels after the need for the glucose ends. (like a muscle contracting.)

The Negative Feedback System for glucose homeostasis is not functioning. The excess glucose is not returning for the storage process after the "need event." This, in very simple terms, is Diabetes.

Let me digress a bit, before I get one of my headaches when I start to think to much! :):)

A Positive Feedback System is Blood Clotting. You want blood clotting to occur and keep occurring at  the site of a good, bleeding scratch or cut to form a scab to prevent further fluids and electrolytes from leaving the body too quickly and not under body control. Since there is not a need to lose body fluids and electrolytes in uncontrolled events (like a severe cut) this system works only one - a positive action to make a clot and scab formation possible.

What happens to Large Molecules after Digestion?

The Mosaic Nature of a Cell Membrane

Have you ever eaten a peanut butter and mayonnaise sandwich? A cell membrane is built sort  of like a sandwich.

It is a double layer of fat sandwiched between two water soluble layers. There are a variety of things that facilitate movement back and forth across this selectively permeable membrane.

The by-products of digestion are monosaccharides (little molecules of sugar) , amino acids (little protein parts) and fats (fatty acids and glycerol.) These little guys have to make it through the cell membrane somehow. 

If the molecule is fairly simple, a concentration gradient is enough. If you have a large number of molecules on one side of a membrane and fewer molecules on the other side the flow of the molecules goes from a high concentration of the molecules to a concentration that is lower.

This is a definition of Simple Diffusion across a selectively permeable membrane. The membrane uses simple diffusion based on concentration gradients.

What happens if one or more of the following prevents or slows down diffusion?

• The molecule is charged. (like an ion.)
• The molecule is too large.
• The molecule is shaped wrong. (a square peg in a round hole.)
• The molecule is water soluble but the membrane has a double lipid layer (think fat). (they are not miscible)
• The molecule is soluble in fats but will not mix with water or water soluble molecules.
• There isn't a concentration gradient or you try to move a molecule against a concentration gradient if a gradient exists.

Since in Diabetes lets see what happens to Glucose, a monosaccharide breakdown product of a complex polysaccharide. 

Glucose is a large molecule that needs the presence of a transporter protein that is unique to glucose. The transporter acts as a signal mechanism that opens an area either on the outside or inside of a cell membrane. 

Imagine a V-shaped structure that opens on the outside of a cell membrane (V) and the glucose molecule, with the assistance of the protein transporter, helps the glucose wedge into the open end of the (V). As soon as the glucose is wedged in the (V) is reversed and the open end of the (V) is now pointing the other way. The glucose molecule is released into the inside of the cell. It is a modified protein tube that passes completely through the mosaic like cell membrane.

It by-passes several of the hinderances to the passage of glucose mentioned above.

By-passes charge, shape, chemical nature, and size (up to a point). Since digestion keeps a steady supply of glucose coming into the system, the concentration gradient is higher on the outside of the mosaic membrane. The glucose molecule follows is concentration gradient.

In fact the cell membrane has a bunch of these holes that make it look like a piece of swiss cheese.

In summary, this is how a large molecule, like glucose, makes its way into a cell or out of a cell.