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Physiology

The Sliding Filament mechanism of muscle contraction.

When a muscle contracts the light I bands disappear and the dark A bands move closer together. This is due to the sliding of the actin and myosin myofilaments against one another. The Z-lines pull together and the sarcomere shortens

 

The thick myosin bands are not single myosin proteins but are made of multiple myosin molecules. Each myosin molecule is composed of two parts: the globular "head" and the elongated "tail". They are arranged to form the thick bands.

It is the myosin heads which form crossbridges that attach to binding sites on the actin molecules and then swivel to bring the Z-lines together

 

Likewise the thin bands are not single actin molecules. Actin is composed of globular proteins (G actin units) arranged to form a double coil (double alpha helix) which produces the thin filament. Each thin myofilament is wrapped by a tropomyosin protein, which in turn is connected to the troponin complex. 

The tropomyosin-troponin combination blocks the active sites on the actin molecules preventing crossbridge formation. The troponin complex consists of three components: TnT, the part which attaches to tropomyosin, TnI, an inhibitory portion which attaches to actin, and TnC which binds calcium ions. When excess calcium ions are released they bind to the TnC causing the troponin-tropomyosin complex to move, releasing the blockage on the active sites. As soon as this happens the myosin heads bind to these active sites.

Respiratory system plays important role in maintaining homeostasis . Other than its major function , which is supplying the cells with needed oxygen to produce energy and getting rid of carbon dioxide , it has other functions :

1 Vocalization , or sound production.
2 Participation in acid base balance .
3 Participation in fluid balance by insensible water elimination (vapors ).
4 Facilitating venous return .
5 Participation in blood pressure regulation : Lungs produce Angiotensin converting enzyme ( ACE ) .
6 Immune function : Lungs produce mucous that trap foreign particles , and have ciliae that move foreign particles away from the lung. They also produce alpha 1 antitrepsin that protect the lungs themselves from the effect of elastase and other proteolytic  enzymes

Serum Proteins

Proteins make up 6–8% of the blood. They are about equally divided between serum albumin and a great variety of serum globulins.

After blood is withdrawn from a vein and allowed to clot, the clot slowly shrinks. As it does so, a clear fluid called serum is squeezed out. Thus:

Serum is blood plasma without fibrinogen and other clotting factors.

The serum proteins can be separated by electrophoresis.

  • The most prominent of these and the one that moves closest to the positive electrode is serum albumin.
  • Serum albumin
    • is made in the liver
    • binds many small molecules for transport through the blood
    • helps maintain the osmotic pressure of the blood
  • The other proteins are the various serum globulins.
    • alpha globulins (e.g., the proteins that transport thyroxine and retinol [vitamin A])
    • beta globulins (e.g., the iron-transporting protein transferrin)
    • gamma globulins.
      • Gamma globulins are the least negatively-charged serum proteins. (They are so weakly charged, in fact, that some are swept in the flow of buffer back toward the negative electrode.)
      • Most antibodies are gamma globulins.
      • Therefore gamma globulins become more abundant following infections or immunizations. 

Serum Lipids

 

LIPID

Typical values (mg/dl)

Desirable (mg/dl)

Cholesterol (total)

170–210

<200

LDL cholesterol

60–140

<100

HDL cholesterol

35–85

>40

Triglycerides

40–160

<160

 

  • Total cholesterol is the sum of
    • HDL cholesterol
    • LDL cholesterol and
    • 20% of the triglyceride value
  • Note that
    • high LDL values are bad, but
    • high HDL values are good.
  • Using the various values, one can calculate a
    cardiac risk ratio = total cholesterol divided by HDL cholesterol
  • A cardiac risk ratio greater than 7 is considered a warning.

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:

  • beta cells, which secrete insulin and amylin;
  • alpha cells, which secrete glucagon;
  • delta cells, which secrete somatostatin, and
  • gamma cells, which secrete a polypeptide of unknown function.

Beta Cells

Beta cells secrete insulin in response to a rising level of blood sugar

Insulin affects many organs. It

  • stimulates skeletal muscle fibers to
    • take up glucose and convert it into glycogen;
    • take up amino acids from the blood and convert them into protein.
  • acts on liver cells
    • stimulating them to take up glucose from the blood and convert it into glycogen while
    • inhibiting production of the enzymes involved in breaking glycogen back down (glycogenolysis) and
    • inhibiting gluconeogenesis; that is, the conversion of fats and proteins into glucose.
  • acts on fat (adipose) cells to stimulate the uptake of glucose and the synthesis of fat.
  • acts on cells in the hypothalamus to reduce appetite.

Diabetes Mellitus

Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:

  • a failure of the kidney to retain glucose .
  • a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).

There are three categories of diabetes mellitus:

  • Insulin-Dependent Diabetes Mellitus (IDDM) (Type 1) and
  • Non Insulin-Dependent Diabetes Mellitus (NIDDM)(Type 2)
  • Inherited Forms of Diabetes Mellitus

Insulin-Dependent Diabetes Mellitus (IDDM)

IDDM ( Type 1 diabetes)

  • is characterized by little or no circulating insulin;
  • most commonly appears in childhood.
  • It results from destruction of the beta cells of the islets.
  • The destruction results from a cell-mediated autoimmune attack against the beta cells.
  • What triggers this attack is still a mystery, although a prior viral infection may be the culprit.

Non Insulin-Dependent Diabetes Mellitus (NIDDM)

Many people develop diabetes mellitus without an accompanying drop in insulin levels In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles. Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter. This transporter forms a channel that permits the facilitated diffusion of glucose into the cell. Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen is reduced. This is called insulin resistance. NIDDM (also called Type 2 diabetes mellitus) usually occurs in adults and, particularly often, in overweight people.

Alpha Cells

The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose (glycogenolysis) which is deposited in the blood.

Glucagon secretion is

  • stimulated by low levels of glucose in the blood;
  • inhibited by high levels, and
  • inhibited by amylin.

The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.

Delta Cells

The delta cells secrete somatostatin. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine.

Gamma Cells

The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.

 Acute Obstructive Disorders
 1.    Heimlich maneuver
 2.    Bypass, tracheostomy w/catheter to suck up secretion

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

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