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Physiology

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) .

Platelets

Platelets are cell fragments produced from megakaryocytes.

Blood normally contains 150,000 to 350,000 per microliter (µl). If this value should drop much below 50,000/µl, there is a danger of uncontrolled bleeding. This is because of the essential role that platelets have in blood clotting.

When blood vessels are damaged, fibrils of collagen are exposed.

  • von Willebrand factor links the collagen to platelets forming a plug of platelets there.
  • The bound platelets release ADP and thromboxane A2 which recruit and activate still more platelets circulating in the blood.
  • (This role of thromboxane accounts for the beneficial effect of low doses of aspirin a cyclooxygenase inhibitor in avoiding heart attacks.)

ReoPro is a monoclonal antibody directed against platelet receptors. It inhibits platelet aggregation and appears to reduce the risk that "reamed out" coronary arteries (after coronary angioplasty) will plug up again.

The Adrenal Glands

The adrenal glands are two small structures situated one at top each kidney. Both in anatomy and in function, they consist of two distinct regions:

  • an outer layer, the adrenal cortex, which surrounds
  • the adrenal medulla.

The Adrenal Cortex

cells of the adrenal cortex secrete a variety of steroid hormones.

  • glucocorticoids (e.g., cortisol)
  • mineralocorticoids (e.g., aldosterone)
  • androgens (e.g., testosterone)
  • Production of all three classes is triggered by the secretion of ACTH from the anterior lobe of the pituitary.

Glucocorticoids

They Effect by raising the level of blood sugar (glucose). One way they do this is by stimulating gluconeogenesis in the liver: the conversion of fat and protein into intermediate metabolites that are ultimately converted into glucose.

The most abundant glucocorticoid is cortisol (also called hydrocortisone).

Cortisol and the other glucocorticoids also have a potent anti-inflammatory effect on the body. They depress the immune response, especially cell-mediated immune responses. 

Mineralocorticoids

The most important of them is the steroid aldosterone. Aldosterone acts on the kidney promoting the reabsorption of sodium ions (Na+) into the blood. Water follows the salt and this helps maintain normal blood pressure.

Aldosterone also

  • acts on sweat glands to reduce the loss of sodium in perspiration;
  • acts on taste cells to increase the sensitivity of the taste buds to sources of sodium.

The secretion of aldosterone is stimulated by:

  • a drop in the level of sodium ions in the blood;
  • a rise in the level of potassium ions in the blood;
  • angiotensin II
  • ACTH (as is that of cortisol)

Androgens

The adrenal cortex secretes precursors to androgens such as testosterone.

Excessive production of adrenal androgens can cause premature puberty in young boys.

In females, the adrenal cortex is a major source of androgens. Their hypersecretion may produce a masculine pattern of body hair and cessation of menstruation.

Addison's Disease: Hyposecretion of the adrenal cortices

Addison's disease has many causes, such as

  • destruction of the adrenal glands by infection;
  • their destruction by an autoimmune attack;
  • an inherited mutation in the ACTH receptor on adrenal cells.

Cushing's Syndrome: Excessive levels of glucocorticoids

In Cushing's syndrome, the level of adrenal hormones, especially of the glucocorticoids, is too high.It can be caused by:

  • excessive production of ACTH by the anterior lobe of the pituitary;
  • excessive production of adrenal hormones themselves (e.g., because of a tumor), or (quite commonly)
  • as a result of glucocorticoid therapy for some other disorder such as
    • rheumatoid arthritis or
    • preventing the rejection of an organ transplant.

The Adrenal Medulla

The adrenal medulla consists of masses of neurons that are part of the sympathetic branch of the autonomic nervous system. Instead of releasing their neurotransmitters at a synapse, these neurons release them into the blood. Thus, although part of the nervous system, the adrenal medulla functions as an endocrine gland.The adrenal medulla releases:

  • adrenaline (also called epinephrine) and
  • noradrenaline (also called norepinephrine)

Both are derived from the amino acid tyrosine.

Release of adrenaline and noradrenaline is triggered by nervous stimulation in response to physical or mental stress. The hormones bind to adrenergic receptors  transmembrane proteins in the plasma membrane of many cell types.

Some of the effects are:

  • increase in the rate and strength of the heartbeat resulting in increased blood pressure;
  • blood shunted from the skin and viscera to the skeletal muscles, coronary arteries, liver, and brain;
  • rise in blood sugar;
  • increased metabolic rate;
  • bronchi dilate;
  • pupils dilate;
  • hair stands on end (gooseflesh in humans);
  • clotting time of the blood is reduced;
  • increased ACTH secretion from the anterior lobe of the pituitary.

All of these effects prepare the body to take immediate and vigorous action.

Oxygen Transport

In adult humans the hemoglobin (Hb) molecule

  • consists of four polypeptides:
    • two alpha (α) chains of 141 amino acids and
    • two beta (β) chains of 146 amino acids
  • Each of these is attached the prosthetic group heme.
  • There is one atom of iron at the center of each heme.
  • One molecule of oxygen can bind to each heme.

The reaction is reversible.

  • Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right. The purple-red deoxygenated hemoglobin of the venous blood becomes the bright-red oxyhemoglobin of the arterial blood.
  • Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted and oxyhemoglobin gives up its oxygen.

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

Transport of Carbon Dioxide

A.    Dissolved in Blood Plasma (7-10%)

B.    Bound to Hemoglobin (20-30%)

1.    carbaminohemoglobin - Carb Dioxide binds to an amino acid on the polypeptide chains

2.    Haldane Effect - the less oxygenated blood is, the more Carb Diox it can carry

a.    tissues - as Oxygen is unloaded, affinity for Carb Dioxide increases
b.    lungs - as Oxygen is loaded, affinity for Carb Dioxide decreases, allowing it to be released

C.    Bicarbonate Ion Form in Plasma (60-70%)

1.    Carbon Dioxide combines with water to form Bicarbonate

CO2 + H2O <==> H2CO3 <==> H+ + HCO3-

2.    carbonic anhydrase - enzyme in RBCs that catalyzes this reaction in both directions

a.    tissues - catalyzes formation of Bicarbonate
b.    lungs - catalyzes formation of Carb Dioxide

3.    Bohr Effect - formation of Bicarbonate (through Carbonic Acid) leads to LOWER pH (H+ increase), and more unloading of Oxygen to tissues

a.    since hemoglobin "buffers" to H+, the actual pH of blood does not change much

4.    Chloride Shift - chloride ions move in opposite direction of the entering/leaving Bicarbonate, to prevent osmotic problems with RBCs

D.    Carbon Dioxide Effects on Blood pH

1.    carbonic acid-bicarbonate buffer system
    
low pH       → HCO3- binds to H+
high pH     →   H2CO3 releases H+
    
2.     low shallow breaths    → HIGH Carb Dioxide    → LOW pH (higher H+)
3.     rapid deep breaths     → LOW Carb Dioxide   → HIGH pH (lower H+)

Maintenance of Homeostasis


The kidneys maintain the homeostasis of several important internal conditions by controlling the excretion of substances out of the body. 

Ions. The kidney can control the excretion of potassium, sodium, calcium, magnesium, phosphate, and chloride ions into urine. In cases where these ions reach a higher than normal concentration, the kidneys can increase their excretion out of the body to return them to a normal level. Conversely, the kidneys can conserve these ions when they are present in lower than normal levels by allowing the ions to be reabsorbed into the blood during filtration. (See more about ions.)
 
pH. The kidneys monitor and regulate the levels of hydrogen ions (H+) and bicarbonate ions in the blood to control blood pH. H+ ions are produced as a natural byproduct of the metabolism of dietary proteins and accumulate in the blood over time. The kidneys excrete excess H+ ions into urine for elimination from the body. The kidneys also conserve bicarbonate ions, which act as important pH buffers in the blood.
 
Osmolarity. The cells of the body need to grow in an isotonic environment in order to maintain their fluid and electrolyte balance. The kidneys maintain the body’s osmotic balance by controlling the amount of water that is filtered out of the blood and excreted into urine. When a person consumes a large amount of water, the kidneys reduce their reabsorption of water to allow the excess water to be excreted in urine. This results in the production of dilute, watery urine. In the case of the body being dehydrated, the kidneys reabsorb as much water as possible back into the blood to produce highly concentrated urine full of excreted ions and wastes. The changes in excretion of water are controlled by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and released by the posterior pituitary gland to help the body retain water.
 
Blood Pressure. The kidneys monitor the body’s blood pressure to help maintain homeostasis. When blood pressure is elevated, the kidneys can help to reduce blood pressure by reducing the volume of blood in the body. The kidneys are able to reduce blood volume by reducing the reabsorption of water into the blood and producing watery, dilute urine. When blood pressure becomes too low, the kidneys can produce the enzyme renin to constrict blood vessels and produce concentrated urine, which allows more water to remain in the blood.

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