Peripheral capillary bed

For drugs deposited in the proximity of the peripheral capillary beds of muscle and subcutaneous tissue, lipid solubility is considerably less important than the oral route since even ionized forms of drugs are absorbed with relative ease. The capillary wall in these areas is of sufficient porosity that even drugs with molecular weights as great as 60,000 daltons may be absorbed by passive diffusion. This explains why a protein, such as insulin (5808 daltons), can be given subcutaneously and is absorbed into the bloodstream. 

The hypothalamic releasing hormones are peptides. They reach their target cells in the AH lobe by way of a portal vascular route consisting of two serially connected capillary beds. The first of these lies in the hypophyseal stalk, the second corresponds to the capillary bed of the AH lobe. Here, the hypothalamic hormones diffuse from the blood to their target cells, whose activity they control. Hormones released from the AH cells enter the blood, in which they are distributed to peripheral organs (1),... 

Hemoglobin binds Oj at the high PO2 (100 mm Hg) of the lung capillary beds and transports it to the peripheral tissues, where Poj is lower (-30 mm Hg) and O2 dissociates from hemoglobin. 

The absorption of drugs in solution from intramuscular and subcutaneous sites of injection is limited by the perfusion rate. Failure to recognize this important concept has resulted in patient death. For example, morphine sulfate is often administered subcutaneously in a dose of 10 mg per 70 kg of body weight. This dose is sufficient to produce analgesia in 70% of patients with moderate to severe pain. However, in the setting of circulatory collapse and shock (e.g., septic shock in bacteremia due to release of endotoxin) in which the peripheral circulation may be impaired, morphine is not absorbed. Cases have been reported in which the lack of analgesia prompted the additional injection of morphine, all of which remained at the injection site and in the subcutaneous capillary bed. When the peripheral circulation improved, the massive amount of morphine that had collected became absorbed and death ensued, which was primarily due to respiratory depression. 

Figure 13.1 Sagittal section film autoradiogram of a mouse killed 5 minutes after intravenous injection of [14C] histamine, a small molecule that readily crosses the porous capillary beds in peripheral tissues, but does not cross the blood-brain barrier (BBB) in brain or spinal cord...

The endothelial cell is an anatomical location of barrier function and of the various saturable dansporters (Figure 4.1). Capillary beds from peripheral dssues have numerous intracellular and intercellular pores and fenestrations and high rates of pinocytosis that account for their leakiness. The brain endothelial cell engages in comparatively little pinocytosis, has few intracellular pores or fenestrations, and intercellular pores or gaps are eliminated because of tight junctions. 

Figure 4.1. Tlie vasculai blood-brain barrier tliree levels of complexity. The upper panel illustrates tlie brain endotlielial cell. Tliis is tlie functional and anatomical site of botli banier function and of saturable and non-saturable mechanisms of passage. The major modifications allowing botli banier function and selective penetration of substances ai e indicated. Tlie middle panel illustrates otlier cell types and sti uc-tures important in BBB function. Pericytes are embedded in a basement membrane and asti ocytes foim a net-like structure over tlie capillary bed. Botli cell types are in paracellular communication witli tlie brain endotlielial cells. Pericytes and asti ocytes to some extent oppose each o tilers effects on BBB functions. Tlie lower panel illusti ates tlie neurovasculai unit, a concept, tliat emphasizes inlegration of peripheral, BBB, and centi al inleractions.

Systemic (Peripheral) Transports oxygenated blood from the left ventricle to the aorta and into the network of arteries. Nutrients and waste products in the blood are exchanged at capillary beds and returned to the heart by the network of veins. 

In the capillary beds of most organs, a rapid passage of molecules occurs from the blood through the endothelial wall of the capillaries into the interstitial fluid. Thus, the composition of interstitial fluid resembles that of blood, and specific receptors or transporters in the plasma membrane of the cells being bathed by the interstitial fluid may directly interact with amino acids, hormones, or other compounds from the blood. In the brain, transcapillary movement of substrates in the peripheral circulation into the brain is highly restricted by the blood-brain barrier. This barrier hmits the accessibility of blood-borne toxins and other potentially harmful compounds to the neurons of the CNS. 

Systemic (peripheral) circulation. In systemic circulation, the heart pumps blood from the left ventricle to the aorta into the general circulation. Blood is carried by the arteries to the arterioles down to the capillary beds where nutrients in the blood are exchanged with waste products at the cellular level. Blood then returns through the venules to the veins back to the heart. 

The absorbed cholesterol leaves the intestine in form of chylomicrons and VLDL. Once entered the general circulation the catabolism of these lipoproteins initially takes place in the capillary bed here, owing to the activation of lipoprotein lipase, the major portion of triglycerides is removed[66]. The products of this peripheric lipolysis are called "remnants and are removed by the liver[67]. Cholesterol from the remnants seems to be the major modulator of cholesterol synthesis in the liver[68]. 

P. falciparum is the most dangerous of the four malaria strains, and can kill a healthy adult in 48 hours. This type is so dangerous because the parasitized red blood cells become sequestered in the deep vascular beds of the brain—Whence the term cerebral malaria for infection with this strain. Sequestration happens because parasite-derived proteins on the surface of infected red blood cells cause them to stick to each other and to the cells lining the host s venules and capillaries (two types of small blood vessel), especially in the brain and heart. This has the effect of keeping the parasite away from the host s natural defense system. It also means that the progress of the disease can be hidden from a health practitioner who draws blood from a peripheral body region (for example, the arm) such blood will not reveal the true extent of the infection. Delirium, convulsions, and coma are features of falciparum malaria, which is associated with a 20% mortality rate in adults. 

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