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Gene & Protein in Disease Albumin (HSA) binding and health

explain nutrition of cells and failure during sepsis [16-18] and flowing directly from the pancreas through the hepatic
multiple organ failure as shown in Figure 3. portal vein (HPV). The result is that liver control of glucose
The HSALNP provides binding from the target (liver) to by insulin from the HPV and pancreas is maintained within
the cells, but ABD occurs when binding of systemic nutrients this fast circulation every few minutes at most.
is impaired. Common manifestations of COVID-19 in The ability to raise or decrease WBF has many clinical
children include non-dermatological age-related symptoms, consequences in almost all areas of medicine. In ABD
such as multisensory inflammation syndrome. Age-related (Figure 4), an increase in albumin levels will gradually
dermatological symptoms change from urticaria in stabilize the HSA diurnal rhythm by settling variations
children under 2 years old to chronic lymphocytic leukemia in the cardiovascular capillary circulation and stabilizing
in the middle teens. Distribution of HSA is known to be cardiovascular output. Once HSA is raised to an appropriate
extensive in the children’s skin, which is a relatively larger concentration, ABD will be reversed as the chain of
organ than that in adults . nutrients supplied by the liver and the complex equilibrium
[1]
of nutrients in the plasma re-establish themselves. In the
3. Raising HSA concentration to correct longer term, the 7-h half-life of the HSALNP, which supplies
deficiencies that cause vulnerabilities in ABD the interstitial spaces and deep cells with nutrients and
Gaseous exchange to cells takes place in the lungs, cells are maintains correct colloidal pressure, will resume providing
supplied from the capillary network, with almost all gaseous interstitial spaces and cells as appropriate.
distribution by direct diffusion. In contrast, metabolites are The HSALNP separates the cardiovascular system into
transferred through the cellular interstitial spaces determined different circulations according to the half-life of substances
by HSA binding and interstitial fluid and lymph flow. transported. Thus, conventionally gaseous respiration
However, over 50% of HSA forms a secondary circulation, provides exchange in minutes to the cells from the lungs.
which has a half-life of many hours, from the leakage of The speed and distribution of all other components in the
HSA through the interstitial spaces into the lymph – this is blood is controlled by the binding levels of albumin; 60% of
the HSALNP. This secondary circuit is fed from the primary which passes into the interstitial spaces and lymph, taking
circuit which is maintained by HSA liver production and is many hours to return to the liver. It is this second longer
dependent upon organ movement. In turn, metabolites such nutrient circulation, which has been overlooked, and the
as glucose and ketones are controlled in the primary circuit timing of which may be weeks. Concentrations of all other
by circulating hormones mainly from the adrenal glands components of the blood respond to changes in HSA and
(cortisol, aldosterone, adrenaline, and noradrenaline) and normalize correspondingly.
pancreas (insulin and glucagon). Long-term maintenance of
glucose is therefore dependent on individual organ’s use of 4. Maintenance of physiologically normal
glucose, organ usage reduces glucose levels which are then HSA levels
detected by the pancreas as the lymph returns to the plasma.
Note that glucose levels are maintained in the fast primary In a healthy body, HSA production in the liver is regulated
cardiocapillary circuit and not the HSALNP with insulin by pressure in the hepatocytes of the liver. Increased levels

• A decrease in HSA binding availability causes albumin‑binding deficiency (ABD), whereby insufficient binding for nutrient affects oncotic pressure
and cellular nutrients.
• ABDs are defined symptoms caused by lack of correct binding to HSA, resulting in illness caused by resulting nutrient deficiency and adverse oncotic
pressure changes.
• Sepsis may well be an ABD similar to metabolic diseases and many cardiac symptoms [2,4,17,18,40] .
• ABDs cause endothelial collapse, and the endothelial glycocalyx plays an important role in vascular homeostasis, regulating vascular permeability and
cell adhesion. It has antithrombotic and anti-inflammatory functions and is bound within the glycocalyx, thus contributing to stability of the layer.
• Proteins that support the glycocalyx like C‑reactive protein which are created in the liver are transported by HSA and become integral to the
endothelial glycocalyx [6,15] .
• HSA also transports sphingosine‑1‑phosphate, which has protective endothelial effects .
[5]
• The human serum albumin lymphatic nutrient pump (HSALNP) distributes nutrients selectively to organs, simultaneously maintaining oncotic pressure [1,2,4,5] .
• Present regimens for saline and colloids do not consider physiological reality [4,5] . Infusion of the periphery can produce cellular damage.
• An appropriate procedure for fluid therapy is by direct infusion to the liver, and the most convenient route is by the hepatic portal vein (HPV)
by ultrasound-guided core needle. Note the HPV is the only site of entry for both insulin and HSA where it is possible to maintain appropriate
concentrations. Dilution of insulin or HSA by infusion at the periphery is predicted to cause insulin resistance as it is primarily fed to the periphery.
Figure 4. Albumin-binding deficiency and an appropriate procedure to overcome it.

Volume 2 Issue 3 (2023) 4 https://doi.org/10.36922/gpd.0328