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Physiology

Oxygen Transport in Blood: Hemoglobin

A.    Association & Dissociation of Oxygen + Hemoglobin

1.    oxyhemoglobin (HbO2) - oxygen molecule bound
2.    deoxyhemoglobin (HHb) - oxygen unbound
    
H-Hb     +    O2  <= === => HbO2 + H+

3.    binding gets more efficient as each O2 binds
4.    release gets easier as each O2 is released

5.    Several factors regulate AFFINITY of O2

a.    Partial Pressure of O2
b.    temperature
c.    blood pH (acidity)
d.    concentration of “diphosphoglycerate” (DPG)

B.    Effects of Partial Pressure of O2

1.  oxygen-hemoglobin dissociation curve

a.    104 mm (lungs) - 100% saturation (20 ml/100 ml)
b.    40 mm (tissues) - 75% saturation (15 ml/100 ml)
c.    right shift - Decreased Affinity, more O2 unloaded
d.     left shift- Increased Affinity, less O2 unloaded


C.    Effects of Temperature
    
1.    HIGHER Temperature    --> Decreased Affinity (right)
2.    LOWER Temperature        --> Increased Affinity (left)

D.    Effects of pH (Acidity) 

1.    HIGHER pH    --> Increased Affinity (left)
2.    LOWER pH    --> Decreased Affinity (right) "Bohr Effect"
a.    more Carbon Dioxide, lower pH (more H+), more O2 release

E.    Effects of Diphosphoglycerate (DPG)

1.    DPG - produced by anaerobic processes in RBCs
2.    HIGHER DPG    > Decreased Affinity (right)
3.    thyroxine, testosterone, epinephrine, NE - increase RBC metabolism and DPG production, cause RIGHT shift

F.    Oxygen Transport Problems

1.    hypoxia - below normal delivery of Oxygen

a.    anemic hypoxia - low RBC or hemoglobin
b.    stagnant hypoxia - impaired/blocked blood flow
c.    hypoxemic hypoxia - poor lung gas exchange

2.    carbon monoxide poisoning - CO has greater Affinity than Oxygen or Carbon Dioxide 
 

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .


Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.
 

CNS PROTECTION

 

- Bones of the Skull       Frontal, Temporal, Parietal, Sphenoid, Occipital

- Cranial Meninges         Dura mater, Arachnoid Space, Pia mater

- Cerebrospinal Fluid

Secreted by Chroid Plexi in Ventricles

Circulation through ventricles and central canal

Lateral and Median apertures from the 4th ventricle into the subarachnoid space

Arachnoid villi of the superior sagittal sinus return CSF to the venous circulation

Hydrocephalic Condition, blockage of the mesencephalic aqueduct, backup of CSF, Insertion of a shunt to drain the excess CSF

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) .

Surface Tension

1.    Maintains stability of alveolus, preventing collapse

2.    Surfactant (Type II pneumocytes) = dipalmityl lecithin

3.    Type II pneumocyte appears at 24 weeks of gestation;
    
1.    Surfactant production, 28-32 weeks;
    2.    Surfactant in amniotic fluid, 35 weeks.
    3.    Laplace equation for thin walled spheres P = 2T
        a.    P = alveolar internal pressure r
        b.    T = tension in the walls r = radius of alveolus
        
4.    During normal tidal respiration

    1.    Some alveoli do collapse (Tidal pressure can't open)
    2.    Higher than normal pressure needed (Coughing)
    3.    Deep breaths & sighs promote re-expansion
    4.    After surgery/Other conditions, Coughing, deep breathing, sustained maximal respiration

Membrane Structure & Function

Cell Membranes

  • Cell membranes are phospholipid bilayers (2 layers)
  • Bilayer forms a barrier to passage of molecules in an out of cell
  • Phospholipids = glycerol + 2 fatty acids + polar molecule (i.e., choline) + phosphate
  • Cholesterol (another lipid) stabilizes cell membranes
  • the hydrophobic tails of the phospholipids (fatty acids) are together in the center of the bilayer. This keeps them out of the water

Membranes Also Contain Proteins

  • Proteins that penetrate the membrane have hydrophobic sections ~25 amino acids long
  • Hydrophobic = doesn't like water = likes lipids
  • Membrane proteins have many functions:
    • receptors for hormones
    • pumps for transporting materials across the membrane
    • ion channels
    • adhesion molecules for holding cells to extracellular matrix

cell recognition antigens

The endocrine system along with the nervous system functions in the regulation of body activities.  The nervous system acts through electrical impulses and neurotransmitters to cause muscle contraction and glandular secretion and interpretation of impulses.  The endocrine system acts through chemical messengers called hormones that influence growth, development, and metabolic activities

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