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.

There are three types of muscle tissue, all of which share some common properties:

• Excitability or responsiveness - muscle tissue can be stimulated by electrical, physical, or chemical means.
• contractility - the response of muscle tissue to stimulation is contraction, or shortening.
• elasticity or recoil - muscles have elastic elements (later we will call these their series elastic elements) which cause them to recoil to their original size.
• stretchability or extensibility - muscles can also stretch and extend to a longer-than-resting length.

The three types of muscle: skeletal, cardiac, and visceral (smooth) muscle.

Skeletal muscle

It is found attached to the bones for movement.

cells are long multi-nucleated cylinders.

 The cells may be many inches long but vary in diameter, averaging between 100 and 150 microns.

 All the cells innervated by branches from the same neuron will contract at the same time and are referred to as a motor unit.

 Skeletal muscle is voluntary because the neurons which innervate it come from the somatic or voluntary branch of the nervous system.

That means you have willful control over your skeletal muscles.

 Skeletal muscles have distinct stripes or striations which identify them and are related to the organization of protein myofilaments inside the cell.

Cardiac muscle

This muscle found in the heart.

 It is composed of much shorter cells than skeletal muscle which branch to connect to one another.

 These connections are by means of gap junctions called intercalated disks which allow an electrochemical impulse to pass to all the connected cells.

 This causes the cells to form a functional network called a syncytium in which the cells work as a unit. Many cardiac muscle cells are myogenic which means that the impulse arises from the muscle, not from the nervous system. This causes the heart muscle and the heart itself to beat with its own natural rhythm.

But the autonomic nervous system controls the rate of the heart and allows it to respond to stress and other demands. As such the heart is said to be involuntary.

Visceral muscle is found in the body's internal organs and blood vessels.

 It is usually called smooth muscle because it has no striations and is therefore smooth in appearance. It is found as layers in the mucous membranes of the respiratory and digestive systems.

It is found as distinct bands in the walls of blood vessels and as sphincter muscles.

Single unit smooth muscle is also connected into a syncytium similar to cardiac muscle and is also partly myogenic. As such it causes continual rhythmic contractions in the stomach and intestine. There and in blood vessels smooth muscle also forms multiunit muscle which is stimulated by the autonomic nervous system. So smooth muscle is involuntary as well

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

The Kidneys

The kidneys are the primary functional organ of the renal system.

They are essential in homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and the regulation of blood pressure (by maintaining salt and water balance).

They serve the body as a natural filter of the blood and remove wastes that are excreted through the urine.

They are also responsible for the reabsorption of water, glucose, and amino acids, and will maintain the balance of these molecules in the body.

In addition, the kidneys produce hormones including calcitriol, erythropoietin, and the enzyme renin, which are involved in renal and hemotological physiological processes.

Anatomical Location

The kidneys are a pair of bean-shaped, brown organs about the size of your fist. They are covered by the renal capsule, which is a tough capsule of fibrous connective tissue.

Right kidney being slightly lower than the left, and left kidney being located slightly more medial than the right.

The right kidneys lie  just below the diaphragm and posterior to the liver, the left below the diaphragm and posterior to the spleen.

Resting on top of each kidney is an adrenal gland (adrenal meaning on top of renal), which are involved in some renal system processes despite being a primarily endocrine organ.

They are considered retroperitoneal, which means that they lie behind the peritoneum, the membrane lining of the abdominal cavity.

The renal artery branches off from the lower part of the aorta and provides the blood supply to the kidneys.

 Renal veins take blood away from the kidneys into the inferior vena cava.

The ureters are structures that come out of the kidneys, bringing urine downward into the bladder.

Internal Anatomy of the Kidneys

There are three major regions of the kidney:

1.         Renal cortex

2.         Renal medulla

3.         Renal pelvis

The renal cortex is a space between the medulla and the outer capsule.

The renal medulla contains the majority of the length of nephrons, the main functional component of the kidney that filters fluid from blood.

The renal pelvis connects the kidney with the circulatory and nervous systems from the rest of the body.

Renal Cortex

The kidneys are surrounded by a renal cortex

The cortex provides a space for arterioles and venules from the renal artery and vein, as well as the glomerular capillaries, to perfuse the nephrons of the kidney. Erythropotein, a hormone necessary for the synthesis of new red blood cells, is also produced in the renal cortex.

Renal Medulla

The medulla is the inner region of the parenchyma of the kidney. The medulla consists of multiple pyramidal tissue masses, called the renal pyramids, which are triangle structures that contain a dense network of nephrons.

At one end of each nephron, in the cortex of the kidney, is a cup-shaped structure called the Bowman's capsule. It surrounds a tuft of capillaries called the glomerulus that carries blood from the renal arteries into the nephron, where plasma is filtered through the capsule.

After entering the capsule, the filtered fluid flows along the proximal convoluted tubule to the loop of Henle and then to the distal convoluted tubule and the collecting ducts, which flow into the ureter. Each of the different components of the nephrons are selectively permeable to different molecules, and enable the complex regulation of water and ion concentrations in the body.

Renal Pelvis

The renal pelvis contains the hilium. The hilum is the concave part of the bean-shape where blood vessels and nerves enter and exit the kidney; it is also the point of exit for the ureters—the urine-bearing tubes that exit the kidney and empty into the urinary bladder. The renal pelvis connects the kidney to the rest of the body.

Supply of Blood and Nerves to the Kidneys

•  The renal arteries branch off of the abdominal aorta and supply the kidneys with blood. The arterial supply of the kidneys varies from person to person, and there may be one or more renal arteries to supply each kidney.

•  The renal veins are the veins that drain the kidneys and connect them to the inferior vena cava.

•  The kidney and the nervous system communicate via the renal plexus. The sympathetic nervous system will trigger vasoconstriction and reduce renal blood flow, while parasympathetic nervous stimulation will trigger vasodilation and increased blood flow.

•  Afferent arterioles branch into the glomerular capillaries, while efferent arterioles take blood away from the glomerular capillaries and into the interlobular capillaries that provide oxygen to the kidney.

•  renal vein

The veins that drain the kidney and connect the kidney to the inferior vena cava.

•  renal artery

These arise off the side of the abdominal aorta, immediately below the superior mesenteric artery, and supply the kidneys with blood.

The large intestine (colon)

The large intestine receives the liquid residue after digestion and absorption are complete. This residue consists mostly of water as well as materials (e.g. cellulose) that were not digested. It nourishes a large population of bacteria (the contents of the small intestine are normally sterile). Most of these bacteria (of which one common species is E. coli) are harmless. And some are actually helpful, for example, by synthesizing vitamin K. Bacteria flourish to such an extent that as much as 50% of the dry weight of the feces may consist of bacterial cells. Reabsorption of water is the chief function of the large intestine. The large amounts of water secreted into the stomach and small intestine by the various digestive glands must be reclaimed to avoid dehydration.

Hemostasis - the  stopping of the blood. Triggered by a ruptured vessel wall it occurs in several steps:

1) vascular spasm - most vessels will constrict strongly when their walls are damaged. This accounts for individuals not bleeding to death even when limbs are crushed. It also can help to enhance blood clotting in less severe injuries.

2) platelet plug - platelets become sticky when they contact collagen, a protein in the basement membrane of the endothelium exposed when the vessel wall is ruptured. As they stick together they can form a plug which will stem the flow of blood in minor vessels.

3) Formation of the Blood Clot:

A) release of platelet factors - as platelets stick together and to the vascular wall some are ruptured releasing chemicals such as thromboxane, PF3, ADP and other substances. These become prothrombin activators. Thromboxane also makes the platelets even stickier, and increases the vascular constriction. These reactions are self perpetuating and become a cascade which represents a positive feedback mechanism.

B) prothrombin activators : prothrombin (already in the blood) is split into smaller products including thrombin, an active protease.

C) thrombin splits soluble fibrinogen, already present in the plasma, into monomers which then polymerize to produce insoluble fibrin threads. The fibrin threads weave the platelets and other cells together to form the actual clot. This occurs within four to six minutes when the injury is severe and up to 15 minutes when it is not. After 15 minutes the clot begins to retract as the fibrin threads contract, pulling the broken edges of the injury together and smoothing the surface of the clot causing the chemical processes to cease. Eventually the clot will dissolve due to enzymes such as plasmin also present in the blood.

The extrinsic pathway: when tissues are damaged the damaged cells release substances called tissue thromboplastin which also acts as a prothrombin activator. This enhances and speeds coagulation when tissue damage is involved.

Anti-thrombin III - this factor helps to prevent clotting when no trigger is present by removing any thrombin present. Its function is magnified many times when heparin is present. Therefore heparin is used clinically as a short-term anticoagulant.

Vitamin K - stimulates the production of clotting factors including prothrombin and fibrinogen in the liver. This vitamin is normally produced by bacteria in the colon. Coumarin (or coumadin) competes with Vitamin K in the liver and is used clinically for long-term suppression of clotting.

Several factors important to clotting are known to be absent in forms of hemophilia. These factors are produced by specific genes which are mutated in the deficient forms. The factors are  VIII, IX, and XI.

Calcium is necessary for blood clotting and its removal from the blood by complexing with citrate will prevent the blood from clotting during storage