Human Albumin metabolism

1. Metabolism of Albumin
dr. Aritantri Daryanami, M.Sc, Sp.PD, K-GEH,
FINASIM

2. Albumin
 The most abundant plasma protein
 Comprises approximately 50–60% of total serum plasma proteins
 Performs multiple functions in the body including maintaining oncotic
pressure as well as binding and transporting molecules.
Moman RN, Gupta N, Varacallo M. Physiology, Albumin. [Updated 2022 Dec 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-
. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459198/?report=classic

3. Physiology of Albumin
 Albumin is initially synthesized by hepatocytes as preproalbumin.
 Then subsequently cleaved to form proalbumin, which is then cleaved to
produce albumin.
 Albumin is water-soluble; the majority of albumin is secreted into the circulation,
with relatively little remaining in the liver.
 In normal physiological settings, albumin has a relatively long half-life of
approximately 21 days and a total turnover time of 25 days.
 The distribution of albumin is approximately 30–40% in the intravascular space
with the remainder in the extravascular space
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol
Rep 23, 11 (2021). https://doi.org/10.1007/s11894-021-00813-6

4. Synthesis of Albumin
 Approximately 10–15 g of albumin are synthesized by the liver daily in a healthy adult.
 Depending on the condition, the liver can increase synthesis of albumin up to 2.7 times its
normal rate.
 The reference range for albumin concentrations in serum is approximately 3.5–5.0 g/dL
and the cases with the concentration less than 3.5 g/dL is usually referred as
hypoalbuminemia
 Insulin has been shown to increase the rate of albumin synthesis and can help to prevent
hypoalbuminemia in patients with diabetes.
 On a genetic level, decreased rates of albumin synthesis can be due to decreased gene
transcription or inhibition of ribosomal aggregation.
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol Rep 23, 11 (2021).
https://doi.org/10.1007/s11894-021-00813-6
Chien, SC., Chen, CY., Lin, CF. et al. Critical appraisal of the role of serum albumin in cardiovascular disease. Biomark Res 5, 31 (2017).
https://doi.org/10.1186/s40364-017-0111-x

5. Synthesis of Albumin
 Factors influencing albumin synthesis:
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol Rep 23, 11 (2021).
https://doi.org/10.1007/s11894-021-00813-6
Chien, SC., Chen, CY., Lin, CF. et al. Critical appraisal of the role of serum albumin in cardiovascular disease. Biomark Res 5, 31 (2017).
https://doi.org/10.1186/s40364-017-0111-x

6. Degradation of Albumin
 Approximately half of albumin is lost into the extravascular spaces, most of which is subsequently
recovered by lymphatic drainage.
 The skin and muscle are the highest sources of extravascular albumin.
 Only very small amounts of albumin are normally lost through the gastrointestinal and renal
systems.
 When found in other fluids in large concentrations, such as in ascites or urine, it is often an
indication of underlying pathology.
 Albumin degradation occurs in various organs throughout the body, although 40–60% of the
breakdown occurs in the skin and muscle.
 The total amount of albumin degraded per day is approximately 14 g in a 70-kg adult.
 The mechanism of breakdown is likely through receptor-mediated lysosomal degradation facilitated
by albumin binding proteins including gp18 and gp30
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol
Rep 23, 11 (2021). https://doi.org/10.1007/s11894-021-00813-6

7. Synthesis and
Degradation of
Albumin
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol Rep 23, 11 (2021). https://doi.org/10.1007/s11894-021-00813-6

8. Hypoalbuminemia - Hyeralbuminemia

9. Human Serum
Albumin

10. Human Serum Albumin
Definition & Function
 Human Serum Albumin is also a colloid fluid administered to patients in need of
fluid resuscitation, especially in the setting of trauma (i.e. hypovolemic shock),
critical ill, or in the setting of large-volume paracentesis.
 The list of drugs transported by albumin includes methadone, propranolol, thiopental, furosemide,
warfarin, methotrexate, alfentanil, and many others.
 Severe liver disease can result in hypoalbuminemia, which leads to fewer available
binding sites for exogenous drugs. This results in larger amounts of unbound
exogenous drugs, which can lead to increased drug sensitivity.
 This sensitivity manifests when patients have serum albumin concentrations lower
than 2.5 g/dL.

11.  Once albumin enters the circulation, about 30% to 40% stays in the
bloodstream, and the remainder enters the interstitial space.
 The majority of protein that leaves the circulation then returns to circulation
via the lymphatic system.
 The circulatory half-life of albumin is 16 hours.
 The majority of albumin’s osmotic effect is attributed to its large molecular weight, while the
rest is thought to stem from its negative charge.
 The negative charge allows albumin to attract positively charged molecules and, ultimately,
water into the intravascular compartment.
By influencing oncotic pressure, albumin has a major influence on capillary membrane
pressure, which is represented by the equation:
CP = (CHP - IHP) - r(COP - IOP)
CP= capillary membrane pressure, CHP= capillary hydrostatic pressure
IHP= interstitial hydrostatic pressure, r= reflection coefficient
COP= the capillary oncotic pressure, IOP= the interstitial oncotic pressure.
Chen, C.B., Hammo, B., Barry, J. et al. Overview of Albumin Physiology and its Role in Pediatric Diseases. Curr Gastroenterol Rep 23, 11 (2021). https://doi.org/10.1007/s11894-021-00813-6

12. Serum Albumin as a Colloid Fluid
 Some clinicians advocate for the use of albumin because it remains intravascular
for longer than crystalloids and theoretically leads to less pulmonary edema.
 Albumin is theoretically advantageous over crystalloids for its potential to increase
a patient’s oncotic pressure.
 The strength albumin has over crystalloids is that it leads to an increase in
intravascular oncotic pressure.
 In cirrhotic patients receiving large volume (more than five liters) paracenteses,
giving the patient 6 gm to 8 gm of albumin for each liter of ascetic fluid drained
could lead to less incidence of hemodynamic compromise.
Moman RN, Gupta N, Varacallo M. Physiology, Albumin. [Updated 2022 Dec 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK459198/?report=classic
Peters T Jr, Stewart AJ. Albumin research in the 21st century. Biochim Biophys Acta. 2013 Dec;1830(12):5351-3. doi: 10.1016/j.bbagen.2013.05.012. PMID: 24094116.

13. Metabolism of Serum Albumin
 Albumin is ultimately degraded into amino acids, which enter the free amino acid pool
(of the total amino acids available for protein synthesis or enegry production).
 Its destruction contributes to about 5% of the total daily protein turnover in the body.
 At a degradation rate of 3.7% per day, an average albumin molecule lives for 27 days,
circulating around the fluid compartments.
 Theodore Jr Peters mentions that albumin molecules collect various small molecules
by covalent binding along their life in the circulation, like "barnacles" collected by "any
tramp steamer doing its rounds".
Moman RN, Gupta N, Varacallo M. Physiology, Albumin. [Updated 2022 Dec 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK459198/?report=classic
Peters T Jr, Stewart AJ. Albumin research in the 21st century. Biochim Biophys Acta. 2013 Dec;1830(12):5351-3. doi: 10.1016/j.bbagen.2013.05.012. PMID: 24094116.

14. Metabolism of Serum Albumin
 The degradation occurs at a rate of 13.3-13.6g/day in a
typical 70kg person.
 The sites of degradation are ubiquitous. The liver
contributes only about 15%. The kidneys degrade 10%,
and a further 10% is lost via leakage into the GI lumen.
 Persisting radiolabels that remain in lysosomes have
demonstrated that muscle and skin are the major sites
of albumin degradation, accounting for 40-60%.
 The major cell types involved seem to be the fibroblasts
and macrophages.
 The degradation rate is increased by catabolism-
inducing hormones, such as corticosteroids.
Peters T Jr, Stewart AJ. Albumin research in the 21st century. Biochim Biophys Acta. 2013 Dec;1830(12):5351-3. doi: 10.1016/j.bbagen.2013.05.012. PMID: 24094116.