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Physiology

Red blood cell cycle:

RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. RBCs require Vitamin B12, folic acid, and iron. The lifespan of RBC averages 120 days. Aged and damaged red cells are disposed of in the spleen and liver by macrophages. The globin is digested and the amino acids released into the blood for protein manufacture; the heme is toxic and cannot be reused, so it is made into bilirubin and removed from the blood by the liver to be excreted in the bile. The red bile pigment bilirubin oxidizes into the green pigment biliverdin and together they give bile and feces their characteristic color. Iron is picked up by a globulin protein (apotransferrin) to be transported as transferrin and then stored, mostly in the liver, as hemosiderin or ferritin. Ferritin is short term iron storage in constant equilibrium with plasma iron carried by transferrin. Hemosiderin is long term iron storage, forming dense granules visible in liver and other cells which are difficult for the body to mobilize.

Some iron is lost from the blood due to hemorrhage, menstruation, etc. and must be replaced from the diet. On average men need to replace about 1 mg of iron per day, women need 2 mg. Apotransferrin (transferrin without the iron) is present in GI lining cells and is also released in the bile. It picks up iron from the GI tract and stimulates receptors on the lining cells which absorb it by pinocytosis. Once through the mucosal cell iron is carried in blood as transferrin to the liver and marrow. Iron leaves the transferrin molecule to bind to ferritin in these tissues. Most excess iron will not be absorbed due to saturation of ferritin, reduction of apotransferrin, and an inhibitory process in the lining tissue.

 

Erythropoietin Mechanism:

Myeloid (blood producing) tissue is found in the red bone marrow located in the spongy bone. As a person ages much of this marrow becomes fatty and ceases production. But it retains stem cells and can be called on to regenerate and produce blood cells later in an emergency. RBCs enter the blood at a rate of about 2 million cells per second. The stimulus for erythropoiesis is the hormone erythropoietin, secreted mostly by the kidney. This hormone triggers more of the pleuripotential stem cells (hemocytoblasts) to follow the pathway to red blood cells and to divide more rapidly.

 

It takes from 3 to 5 days for development of a reticulocyte from a hemocytoblast. Reticulocytes, immature rbc, move into the circulation and develop over a 1 to 2 day period into mature erythrocytes. About 1 to 2 % of rbc in the circulation are reticulocytes, and the exact percentage is a measure of the rate of erythropoiesis.

A rise in blood pressure stretches the atria of the heart. This triggers the release of atrial natriuretic peptide (ANP). ANP is a peptide of 28 amino acids. ANP lowers blood pressure by:

  • relaxing arterioles
  • inhibiting the secretion of renin and aldosterone
  • inhibiting the reabsorption of sodium ions in the collecting ducts of the kidneys.

The effects on the kidney reduce the reabsorption of water by them thus increasing the flow of urine and the amount of sodium excreted in it (These actions give ANP its name: natrium = sodium; uresis = urinate). The net effect of these actions is to reduce blood pressure by reducing the volume of blood volume in the system.

The Heartbeat

During rest, the heart beats about 70 times a minute in the adult male, while pumping about 5 liters of blood.

The stimulus that maintains this rhythm is self-contained. Embedded in the wall of the right atrium is a mass of specialized heart tissue called the sino-atrial (S-A) node. The S-A node is also called the pacemaker because it establishes the basic frequency at which the heart beats.

The interior of the fibers of heart muscle, like all cells, is negatively charged with respect to the exterior. In the cells of the pacemaker, this charge breaks down spontaneously about 70 times each minute. This, in turn, initiates a similar discharge of the nearby muscle fibers of the atrium. A tiny wave of current sweeps over the atria, causing them to contract.

When this current reaches the region of insulating connective tissue between the atria and the ventricles, it is picked up by the A-V node (atrio-ventricular node). This leads to a system of branching fibers that carries the current to all parts of the ventricles.

The contraction of the heart in response to this electrical activity creates systole.

A period of recovery follows called diastole.

  • The heart muscle and S-A node become recharged.
  • The heart muscle relaxes.
  • The atria refill. 

The Electrocardiogram

The electrical activity of the heart can be detected by electrodes placed at the surface of the body. Analysis of an electrocardiogram (ECG or EKG) aids in determining, for example, the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG

Control of the Heart

Although the A-V node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain.

  • One sends nerve impulses down accelerator nerves.
  • The other sends nerve impulses down a pair of vagus nerves

Accelerator Nerves

The accelerator nerves are part of the sympathetic branch of the autonomic nervous system, and  like all post-ganglionic sympathetic neurons  release noradrenaline at their endings on the heart.

They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute. The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25-30 liters/minute.


Vigorous exercise accelerates heartbeat in two ways;

  • As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta, and these transmit impulses to the medulla for relay  by the accelerator nerves  to the heart.
  • As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These, too, send impulses to the medulla for relay to the heart.

Distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP) which initiates a set of responses leading to a lowering of blood pressure

The Vagus Nerves

The vagus nerves are part of the parasympathetic branch of the autonomic nervous system. They, too, run from the medulla oblongata to the heart. Their activity slows the heartbeat.

Pressure receptors in the aorta and carotid arteries send impulses to the medulla which relays these  by way of the vagus nerves  to the heart. Heartbeat and blood pressure diminish.

Blood is a liquid tissue. Suspended in the watery plasma are seven types of cells and cell fragments.

  • red blood cells (RBCs) or erythrocytes
  • platelets or thrombocytes
  • five kinds of white blood cells (WBCs) or leukocytes
    • Three kinds of granulocytes
      • neutrophils
      • eosinophils
      • basophils
    • Two kinds of leukocytes without granules in their cytoplasm
      • lymphocytes
      • monocytes

Factors , affecting glomerular filtration rate :

 Factors that may influence the different pressure forces , or the filtration coefficient will affect the glomerular filtration rate . 
 
1. Dehydration : Causes decrease hydrostatic pressure , and thus decreases GFR
2- Liver diseases that may decrease the plasma proteins and decrease the oncotic pressure , and thus increases glomerular filtration rate .
3- Sympathetic stimulation : will decrease the diameter of afferent arteriole and thus decreases glomerular filtration rate.
4- Renal diseases : Nephrotic syndrome for example decreases the number of working nephrons and thus decreases the filtration coefficient and thus decreases the glomerular filtration rate.
Glomerulonephritis will causes thickening of the glomerular basement membrane and thus decreases the glomerular filtration rate by decreasing the filtration coefficient too.

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

  • Intracellular (inside cells) = ~ 34 liters
  • Interstitial (outside cells) = ~ 13 liters
  • Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

  • Capillary walls (1 cell thick) separate blood from interstitial fluid
  • Cell membranes separate intracellular and interstitial fluids
  • Loss of about 30% of body water is fatal

 

Ions = atoms or molecules with unequal numbers of electrons and protons:

  • found in both intra- & extracellular fluid
  • examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

  • Giving up electron leaves a + charge (cation)
  • Taking on electron produces a - charge (anion)
  • Ions conduct electricity
  • Without ions there can be no nerves or excitability
    • Na+ and K+ cations  
    • Ca2+ and Mg2+ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

  • High K+ in cells, high Na+ outside
  • Ion gradients maintained by Na pump (1/3 of basal metabolism)
  • Think of Na+ gradient as a Na+ battery- stored electrical energy
  • K+ gradient forms a K+ battery
  • Energy stored in Na+ and K+ batteries can be tapped when ions flow
  • Na+ and K+ produce action potential of excitable cells

Asthma = Reversible Bronchioconstruction 4%-5% of population
    Extrinsic / Atopic = Allergic, inherited (familia), chromosome 11
    IgE, Chemical Mediators of inflammation
    
a.    Intrinsic = Negative for Allergy, Normal IgE, Negative Allergic Tests

    Nucleotide Imbalance cAMP/cGMP: cAMP = Inhibits mediator release, cGMP = Facilitates mediator release
b.    Intolerance to Asprin (Triad Asthma)
c.    Nasal Polyps & Asthma

d.    Treatment cause, Symptoms in Acute Asthma
    1.    Bronchial dilators
    2.    steroids edema from Inflamation
    3.    Bronchiohygene to prevent Secondary Infection, (Remove Excess Mucus)
    4.    Education

The Body Regulates pH in Several Ways

  • Buffers are weak acid mixtures (such as bicarbonate/CO2) which minimize pH change
    • Buffer is always a mixture of 2 compounds
      • One compound takes up H ions if there are too many (H acceptor)
      • The second compound releases H ions if there are not enough (H donor)
    • The strength of a buffer is given by the buffer capacity
      • Buffer capacity is proportional to the buffer concentration and to a parameter known as the pK
    • Mouth bacteria produce acids which attack teeth, producing caries (cavities). People with low buffer capacities in their saliva have more caries than those with high buffer capacities.
  • CO2 gas (a potential acid) is eliminated by the lungs
  • Other acids and bases are eliminated by the kidneys

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