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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) .
 

Concentration versus diluting urine 

Kidney is a major route for eliminating fluid from the body to accomplish water balance. Urine excretion is the last step in urine formation. Everyday both kidneys excrete about 1.5 liters of urine.
Depending on the hydrated status of the body, kidney either excretes concentrated urine ( if the plasma is hypertonic like in dehydrated status ) or diluted urine ( if the plasma is hypotonic) .
This occurs thankful to what is known as countercurrent multiplying system, which functions thankfully to establishing large vertical osmotic gradient .
To understand this system, lets review the following facts:
1. Descending limb of loop of Henle is avidly permeable to water.
2. Ascending limb of loop of Henly is permeable to electrolytes , but impermeable to water. So fluid will not folow electrolytes by osmosis.and thus Ascending limb creates hypertonic interstitium that will attract water from descending limb.
Pumping of electrolytes
3. So: There is a countercurrent flow produced by the close proximity of the two limbs.                   
                                                   
Juxtamedullary nephrons have long loop of Henle that dips deep in the medulla , so the counter-current system is more obvious and the medullary interstitium is always hypertonic . In addition, peritubular capillaries in the medulla are straigh ( vasa recta) in which flow is rapid and rapidly reabsorb water maintaining hypertonic medullary interstitium.

In distal tubules water is diluted. If plasma is hypertonic, this will lead to release of ADH by hypothalamus, which will cause reabsorption of water in collecting tubules and thus excrete concentrated urine.

If plasma is hypotonic ADH will be inhibited and the diluted urine in distal  tubules will be excreted as diluted urine.

Urea  contributes to concentrating and diluting of urine as follows:

Urea is totally filtered and then 50% of filtrated urea will be reabsorbed to the interstitium, this will increase the osmolarity of medullary interstitium ( becomes hypertonic ). Those 50% will be secreted in ascending limb of loop of Henle back to tubular fluid to maintain osmolarity of tubular fluid. 55% of urea in distal nephron will be reabsorbed in collecting ducts back to the interstitium ( under the effect of ADH too) . This urea cycle additionally maintain hypertonic interstitium.

Production of Hormones

The kidneys produce and interact with several hormones that are involved in the control of systems outside of the urinary system.

Calcitriol. Calcitriol is the active form of vitamin D in the human body. It is produced by the kidneys from precursor molecules produced by UV radiation striking the skin. Calcitriol works together with parathyroid hormone (PTH) to raise the level of calcium ions in the bloodstream. When the level of calcium ions in the blood drops below a threshold level, the parathyroid glands release PTH, which in turn stimulates the kidneys to release calcitriol. Calcitriol promotes the small intestine to absorb calcium from food and deposit it into the bloodstream. It also stimulates the osteoclasts of the skeletal system to break down bone matrix to release calcium ions into the blood.
 
Erythropoietin. Erythropoietin, also known as EPO, is a hormone that is produced by the kidneys to stimulate the production of red blood cells. The kidneys monitor the condition of the blood that passes through their capillaries, including the oxygen-carrying capacity of the blood. When the blood becomes hypoxic, meaning that it is carrying deficient levels of oxygen, cells lining the capillaries begin producing EPO and release it into the bloodstream. EPO travels through the blood to the red bone marrow, where it stimulates hematopoietic cells to increase their rate of red blood cell production. Red blood cells contain hemoglobin, which greatly increases the blood’s oxygen-carrying capacity and effectively ends the hypoxic conditions.
 
Renin. Renin is not a hormone itself, but an enzyme that the kidneys produce to start the renin-angiotensin system (RAS). The RAS increases blood volume and blood pressure in response to low blood pressure, blood loss, or dehydration. Renin is released into the blood where it catalyzes angiotensinogen from the liver into angiotensin I. Angiotensin I is further catalyzed by another enzyme into Angiotensin II.

Angiotensin II stimulates several processes, including stimulating the adrenal cortex to produce the hormone aldosterone. Aldosterone then changes the function of the kidneys to increase the reabsorption of water and sodium ions into the blood, increasing blood volume and raising blood pressure. Negative feedback from increased blood pressure finally turns off the RAS to maintain healthy blood pressure levels.

A small fraction of cardiac muscle fibers have myogenicity and autorhythmicity.

Myogenicity is the property of spontaneous impulse generation. The slow sodium channels are leaky and cause the polarity to spontaneously rise to threshold for action potential generation. The fastest of these cells, those in the SA node, set the pace for the heartbeat.

Autorhythmicity - the natural rhythm of spontaneous depolarization. Those with the fastest autorhythmicity act as the 1. heart's pacemaker.

Contractility - like skeletal muscle, most cardiac muscle cells respond to stimuli by contracting. The autorhythmic cells have very little contractility however. Contractility in the other cells can be varied by the effect of neurotransmitters.

Inotropic effects - factors which affect the force or energy of muscular contractions. Digoxin, epinephrine, norepinephrine, and dopamine have positive inotropic effects. Betal blockers and calcium channel blockers have negative inotropic effects 

Sequence of events in cardiac conduction: The electrical events in the cardiac cycle.

1) SA node depolarizes and the impulse spreads across the atrial myocardium and through the internodal fibers to the AV node. The atrial myocardium depolarizes resulting in atrial contraction, a physical event.

2) AV node picks up the impulse and transfers it to the AV Bundle (Bundle of His). This produces the major portion of the delay seen in the cardiac cycle. It takes approximately .03 sec from SA node depolarization to the impulse reaching the AV node, and .13 seconds for the impulse to get through the AV node and reach the Bundle of His. Also during this period the atria repolarize.

3) From the AV node the impulse travels through the bundle branches and through the Purkinje fibers to the ventricular myocardium, causing ventricular depolarization and ventricular contraction, a physical event.

4) Ventricular repolarization occurs.

White Blood Cells (leukocytes)

White blood cells

  • are much less numerous than red (the ratio between the two is around 1:700),
  • have nuclei,
  • participate in protecting the body from infection,
  • consist of lymphocytes and monocytes with relatively clear cytoplasm, and three types of granulocytes, whose cytoplasm is filled with granules.

Lymphocytes: There are several kinds of lymphocytes, each with different functions to perform , 25% of wbc The most common types of lymphocytes are

  • B lymphocytes ("B cells"). These are responsible for making antibodies.
  • T lymphocytes ("T cells"). There are several subsets of these:
    • inflammatory T cells that recruit macrophages and neutrophils to the site of infection or other tissue damage
    • cytotoxic T lymphocytes (CTLs) that kill virus-infected and, perhaps, tumor cells
    • helper T cells that enhance the production of antibodies by B cells

Although bone marrow is the ultimate source of lymphocytes, the lymphocytes that will become T cells migrate from the bone marrow to the thymus where they mature. Both B cells and T cells also take up residence in lymph nodes, the spleen and other tissues where they

  • encounter antigens;
  • continue to divide by mitosis;
  • mature into fully functional cells.

Monocytes : also originate in marrow, spend up to 20 days in the circulation, then travel to the tissues where they become macrophages. Macrophages are the most important phagocyte outside the circulation. Monocytes are about 9% of normal wbc count

Macrophages are large, phagocytic cells that engulf

  • foreign material (antigens) that enter the body
  • dead and dying cells of the body.

Neutrophils

The most abundant of the WBCs. about 65% of normal white count  These cells spend 8 to 10 days in the circulation making their way to sites of infection etc  Neutrophils squeeze through the capillary walls and into infected tissue where they kill the invaders (e.g., bacteria) and then engulf the remnants by phagocytosis. They have two types of granules: the most numerous are specific granules which contain bactericidal agents such as lysozyme; the azurophilic granules are lysosomes containing peroxidase and other enzymes

Eosinophils : The number of eosinophils in the blood is normally quite low (0–450/µl). However, their numbers increase sharply in certain diseases, especially infections by parasitic worms. Eosinophils are cytotoxic, releasing the contents of their granules on the invader.

Basophils : rare except during infections where these cells mediate inflammation by secreting histamine and heparan sulfate (related to the anticoagulant heparin). Histamine makes blood vessels permeable and heparin inhibits blood clotting. Basophils are functionally related to mast cells.  . The mediators released by basophils also play an important part in some allergic responses such as hay fever and an anaphylactic response to insect stings.

Thrombocytes (platelets):

Thrombocytes are cellular derivatives from megakaryocytes which contain factors responsible for the intrinsic clotting mechanism. They represent fragmented cells  which contain residual organelles including rough endoplasmic reticulum and Golgi apparati. They are only 2-microns in diameter, are seen in peripheral blood either singly or, often, in clusters, and have a lifespan of 10 days.

Cell, or Plasma, membrane

  • Structure - 2 primary building blocks include

protein (about 60% of the membrane) and lipid, or

fat (about 40% of the membrane).

The primary lipid is called phospholipids, and molecules of phospholipid form a 'phospholipid bilayer' (two layers of phospholipid molecules). This bilayer forms because the two 'ends' of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):

  • Functions include:
    • supporting and retaining the cytoplasm
    • being a selective barrier .
    • transport
    • communication (via receptors)

  • Partial Pressures of O2 and CO2 in the body (normal, resting conditions):

  • Alveoli
    • PO2 = 100 mm Hg
    • PCO2 = 40 mm Hg
  • Alveolar capillaries
    • Entering the alveolar capillaries
      • PO2 = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
      • PCO2 = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 
  • While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

  • Leaving the alveolar capillaries
    • PO2 = 100 mm Hg
    • PCO2 = 40 mm Hg
  • Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
    • Entering the systemic capillaries
      • PO2 = 100 mm Hg
      • PCO2 = 40 mm Hg
    • Body cells (resting conditions)
      • PO2 = 40 mm Hg
      • PCO2 = 45 mm Hg
  • Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
    • Leaving the systemic capillaries
      • PO2 = 40 mm Hg
      • PCO2 = 45 mm Hg
  • Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

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