Clinical Physiology 

Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .

To understand the pathophysiology  of the heart failure ,  lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume

Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload    (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .

Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .

Contractility : Reducing the power of contraction such as in  myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .

Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.

Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility  . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff  .

The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .

The Parathyroid Glands

The parathyroid glands are 4 tiny structures embedded in the rear surface of the thyroid gland. They secrete parathyroid hormone (PTH) a polypeptide of 84 amino acids. PTH increases the concentration of Ca²⁺ in the blood in three ways. PTH promotes

• release of Ca²⁺ from the huge reservoir in the bones. (99% of the calcium in the body is incorporated in our bones.)
• reabsorption of Ca²⁺ from the fluid in the tubules in the kidneys
• absorption of Ca²⁺ from the contents of the intestine (this action is mediated by calcitriol, the active form of vitamin D.)

PTH also regulates the level of phosphate in the blood. Secretion of PTH reduces the efficiency with which phosphate is reclaimed in the proximal tubules of the kidney causing a drop in the phosphate concentration of the blood.

Hyperparathyroidism

Elevate the level of PTH causing a rise in the level of blood Ca²⁺ .Calcium may be withdrawn from the bones that they become brittle and break.

 Patients with this disorder have high levels of Ca²⁺ in their blood and excrete small amounts of Ca²⁺ in their urine. This causes hyperparathyroidism.

Hypoparathyroidism

This disorder have low levels of Ca²⁺ in their blood and excrete large amounts of Ca²⁺ in their urine.

Hyperventilation

1. Treatments :Rebreath air, hold breath (Increase CO₂)
   Give oxygen for Hypoxemia

The Nerve Impulse

When a nerve is stimulated the resting potential changes. Examples of such stimuli are pressure, electricity, chemicals, etc. Different neurons are sensitive to different stimuli(although most can register pain). The stimulus causes sodium ion channels to open. The rapid change in polarity that moves along the nerve fiber is called the "action potential." In order for an action potential to occur, it must reach threshold. If threshold does not occur, then no action potential can occur. This moving change in polarity has several stages:

Depolarization

The upswing is caused when positively charged sodium ions (Na+) suddenly rush through open sodium gates into a nerve cell. The membrane potential of the stimulated cell undergoes a localized change from -55 millivolts to 0 in a limited area. As additional sodium rushes in, the membrane potential actually reverses its polarity so that the outside of the membrane is negative relative to the inside. During this change of polarity the membrane actually develops a positive value for a moment(+30 millivolts). The change in voltage stimulates the opening of additional sodium channels (called a voltage-gated ion channel). This is an example of a positive feedback loop.

Repolarization

The downswing is caused by the closing of sodium ion channels and the opening of potassium ion channels. Release of positively charged potassium ions (K+) from the nerve cell when potassium gates open. Again, these are opened in response to the positive voltage--they are voltage gated. This expulsion acts to restore the localized negative membrane potential of the cell (about -65 or -70 mV is typical for nerves).

Hyperpolarization

When the potassium ions are below resting potential (-90 mV). Since the cell is hyper polarized, it goes to a refractory phrase.

Refractory phase

The refractory period is a short period of time after the depolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to its normal resting potential. The sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized. This refractory area explains why action potentials can only move forward from the point of stimulation.

Factors that affect sensitivity and speed

Sensitivity

Increased permeability of the sodium channel occurs when there is a deficit of calcium ions. When there is a deficit of calcium ions (Ca+2) in the interstitial fluid, the sodium channels are activated (opened) by very little increase of the membrane potential above the normal resting level. The nerve fiber can therefore fire off action potentials spontaneously, resulting in tetany. This could be caused by the lack of hormone from parathyroid glands. It could also be caused by hyperventilation, which leads to a higher pH, which causes calcium to bind and become unavailable.

Speed of Conduction

This area of depolarization/repolarization/recovery moves along a nerve fiber like a very fast wave. In myelinated fibers, conduction is hundreds of times faster because the action potential only occurs at the nodes of Ranvier (pictured below in 'types of neurons') by jumping from node to node. This is called "saltatory" conduction. Damage to the myelin sheath by the disease can cause severe impairment of nerve cell function. Some poisons and drugs interfere with nerve impulses by blocking sodium channels in nerves. See discussion on drug at the end of this outline.

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.

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.