Serum Albumin: A Multifaceted Biomarker and Its Critical Role in Geriatric Hip Fracture Patients

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Abstract

Serum albumin, the most abundant protein in human blood plasma, represents a cornerstone of physiological homeostasis, orchestrating vital functions ranging from the maintenance of intravascular oncotic pressure and the intricate transport of myriad endogenous and exogenous substances to the sophisticated modulation of antioxidant defense and immune system support. Its concentration in the bloodstream serves as a dynamic and highly sensitive biomarker, providing invaluable insights into an individual’s nutritional status, hepatic synthetic capacity, systemic inflammatory burden, and overall physiological resilience. This comprehensive report meticulously explores the multifaceted roles of serum albumin, elucidating its intricate biochemical mechanisms and physiological contributions. Furthermore, it critically examines the profound prognostic significance of serum albumin levels, particularly their protective role against heightened mortality and severe postoperative complications in the uniquely vulnerable population of geriatric hip fracture patients, advocating for its crucial consideration in clinical assessment and management strategies.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

1. Introduction

Serum albumin, a globular, water-soluble, non-glycosylated protein, constitutes approximately 50-60% of the total protein content in human plasma, typically present at concentrations ranging from 35 to 50 g/L (or 3.5 to 5.0 g/dL) (Gounden & Vashisht, 2023). Synthesized predominantly by hepatocytes in the liver at a remarkable rate of approximately 10-15 grams per day in healthy adults, it boasts a relatively long half-life of around 15 to 20 days (Roche & Rondepierre, 2012). This extensive half-life allows it to reflect nutritional and physiological states over a period of weeks rather than days, making it a valuable long-term indicator. Its unique structural characteristics, including its single polypeptide chain comprising 585 amino acid residues and numerous binding sites, underpin its extraordinary functional versatility (Peters, 1996).

Historically, the understanding of albumin’s importance dates back to the mid-19th century when scientists recognized its role in maintaining blood volume. Over time, advancements in biochemical analysis have unveiled its diverse and indispensable functions, positioning it as far more than a simple osmotic agent. Beyond its well-established roles in oncotic pressure regulation and transport, albumin actively participates in maintaining acid-base balance, exerting potent antioxidant effects, and modulating inflammatory and immune responses (Fan et al., 2021). Consequently, variations in serum albumin levels, particularly decreases (hypoalbuminemia), are not merely isolated laboratory findings but rather critical indicators of underlying pathological processes, including malnutrition, chronic disease, acute inflammation, and organ dysfunction (Gibbs et al., 2008).

In the geriatric population, which often presents with complex comorbidities, diminished physiological reserves, and increased susceptibility to stress, serum albumin levels take on heightened clinical significance. Hip fractures, a common and devastating injury in older adults, are frequently complicated by a cascade of systemic responses, including acute inflammatory states, prolonged immobilization, and heightened metabolic demands. In this context, serum albumin has emerged as a particularly potent and consistently observed prognostic factor, influencing outcomes ranging from immediate postoperative morbidity to long-term mortality and functional recovery (Foss & Doblmeier, 2022). Understanding the multifaceted roles of albumin and its implications in this vulnerable patient group is paramount for optimizing clinical assessment, guiding therapeutic interventions, and ultimately improving patient outcomes.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

2. Functions of Serum Albumin

Serum albumin’s extensive array of physiological functions underscores its central role in maintaining systemic homeostasis. These functions are intimately linked to its unique structural properties, including its high concentration in plasma, multiple binding sites, and reactive thiol group.

2.1 Maintenance of Oncotic Pressure

One of the most critical and quantitatively significant functions of serum albumin is its contribution to the maintenance of plasma oncotic pressure (also known as colloid osmotic pressure). Oncotic pressure is the osmotic pressure exerted by colloids (proteins) in a solution, which tends to pull water into the circulatory system (Levick & Michel, 2010). Albumin, due to its relatively large size, anionic charge, and high concentration, accounts for approximately 75-80% of the total oncotic pressure of plasma. This pressure is a crucial component of the Starling forces, which govern fluid exchange across capillary membranes, ensuring the proper distribution of water between the intravascular and interstitial compartments (Michel & Neal, 1999).

Capillary walls are permeable to water and small solutes but largely impermeable to large proteins like albumin. This differential permeability creates an osmotic gradient. Plasma oncotic pressure, exerted by albumin, opposes capillary hydrostatic pressure, which pushes fluid out of the capillaries. A delicate balance between these forces is essential for maintaining intravascular volume and preventing excessive fluid leakage into the interstitial space. When serum albumin levels fall significantly (hypoalbuminemia), the plasma oncotic pressure decreases, leading to a net movement of fluid from the capillaries into the interstitial space. This results in generalized edema, particularly evident in dependent areas such as the ankles and sacrum, and can also lead to effusions in body cavities like ascites (abdominal cavity) or pleural effusions (lung cavity) (Roche & Rondepierre, 2012). Such fluid imbalances can severely compromise tissue perfusion, organ function, and overall patient recovery, especially in stressed physiological states.

2.2 Transport Functions

Albumin serves as the principal carrier protein in plasma for a vast array of endogenous and exogenous substances, facilitating their solubilization, distribution, and bioavailability throughout the body (Fan et al., 2021). Its remarkable versatility as a transport molecule stems from its multiple binding sites with varying affinities for different ligands.

• Hormones: Albumin transports various hydrophobic hormones, including thyroid hormones (thyroxine and triiodothyronine), steroid hormones (cortisol, aldosterone, estrogen, progesterone, and testosterone), and certain peptide hormones. While specific binding globulins exist for many of these, albumin’s high concentration ensures that it carries a significant fraction, influencing their free (biologically active) concentrations and tissue distribution (Peters, 1996).

• Fatty Acids: Free fatty acids, which are largely insoluble in aqueous solution, are crucial energy substrates. Albumin provides multiple high-affinity binding sites for long-chain fatty acids, enabling their efficient transport from adipose tissue to metabolically active tissues such as the heart and skeletal muscle for beta-oxidation and energy production (Roche & Rondepierre, 2012). This transport mechanism is vital, particularly during fasting or periods of high energy demand.

• Bilirubin: Unconjugated bilirubin, a toxic byproduct of heme metabolism, is highly insoluble in water. Albumin binds unconjugated bilirubin tightly, preventing its deposition in tissues, particularly in the brain (kernicterus in neonates), and facilitates its transport to the liver for conjugation and subsequent excretion (Peters, 1996). Impaired albumin binding capacity can lead to increased free bilirubin and associated toxicity.

• Drugs: Albumin binds a wide range of pharmaceutical agents, particularly acidic and neutral drugs, profoundly influencing their pharmacokinetics. The extent of drug binding to albumin affects its distribution volume, metabolic clearance, and renal excretion. Only the unbound fraction of a drug is pharmacologically active and available for diffusion across membranes to target tissues (Bouchard et al., 2013). Thus, hypoalbuminemia can lead to higher free drug concentrations, potentially increasing the therapeutic effect or, critically, the risk of toxicity for highly protein-bound drugs (e.g., warfarin, phenytoin, digoxin, NSAIDs). This is a significant consideration in patient populations with altered albumin levels, such as the elderly or critically ill.

• Metal Ions: Albumin binds and transports various metal ions, including copper (e.g., to form ceruloplasmin), zinc, and calcium. Its calcium-binding capacity is particularly significant, as approximately 40-50% of serum calcium is bound to albumin. Changes in albumin levels directly affect the total serum calcium concentration, necessitating correction formulas for accurate assessment of physiologically active ionized calcium (Dickerson, 2011).

• Other Substances: Albumin also transports bile acids, certain vitamins (e.g., fat-soluble vitamins A, D, E, K), nitric oxide (as S-nitrosothiols, contributing to vasoregulation), and various toxins and waste products, aiding in their detoxification and elimination.

2.3 Antioxidant Properties

Serum albumin is a potent extracellular antioxidant, playing a crucial role in mitigating oxidative stress, a pathological condition characterized by an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them (Fan et al., 2021). The primary mechanism underlying albumin’s antioxidant activity is attributed to its unique single free thiol group located at cysteine residue 34 (Cys34) (Roche & Rondepierre, 2012).

• Thiol Group Scavenging: The Cys34 thiol group is highly reactive and readily participates in redox reactions. It acts as a sacrificial scavenger, reacting directly with various ROS, including hydroxyl radicals, hydrogen peroxide, and peroxynitrite. In doing so, it gets oxidized, protecting more vital cellular components from oxidative damage (Taoufiq et al., 2019). The oxidation products of Cys34 include sulfenic, sulfinic, and sulfonic acids, which can be further reduced or excreted.

• Metal Ion Binding: Albumin’s ability to bind transition metal ions such as copper and iron is another critical aspect of its antioxidant defense. Free transition metals can catalyze the formation of highly damaging hydroxyl radicals via Fenton and Haber-Weiss reactions (Roche & Rondepierre, 2012). By sequestering these metal ions, albumin effectively prevents them from participating in pro-oxidant reactions, thereby reducing oxidative damage to lipids, proteins, and DNA.

• Binding to Hydrophobic Antioxidants: Albumin also serves as a carrier for hydrophobic antioxidants such as bilirubin, uric acid, and various phytochemicals, facilitating their transport and enhancing their antioxidant efficacy throughout the circulation.

In conditions of acute illness, inflammation, or critical stress, oxidative stress is significantly amplified. A decline in functional albumin levels due to reduced synthesis or increased consumption of its antioxidant capacity can therefore exacerbate oxidative damage, contributing to organ dysfunction and systemic complications.

2.4 Immune System Support and Anti-inflammatory Properties

Beyond its direct antioxidant roles, albumin actively contributes to immune defense and modulates inflammatory responses (Fan et al., 2021). While not traditionally classified as an immune protein, its influence is pervasive.

• Toxin and Pathogen Binding: Albumin has the capacity to bind and neutralize a wide array of microbial toxins (e.g., bacterial endotoxins like lipopolysaccharide, LPS), exotoxins, and even certain viruses. By binding these harmful agents, albumin can prevent their interaction with host cells, reduce their systemic distribution, and facilitate their clearance, thereby limiting their pathogenic effects (Peters, 1996).

• Modulation of Inflammation: Albumin is considered a negative acute-phase reactant, meaning its synthesis decreases during acute inflammation. However, paradoxically, it also exerts significant anti-inflammatory effects. It can bind to and sequester pro-inflammatory mediators, such as nitric oxide, cytokines (e.g., IL-6, TNF-α), and complement components, thereby attenuating their inflammatory actions (Arturson & Grotte, 1990). Furthermore, its antioxidant properties directly combat inflammation-induced oxidative stress, forming a feedback loop that helps to resolve inflammation.

• Support for Immune Cell Function: By maintaining oncotic pressure, albumin ensures adequate tissue perfusion, which is vital for the delivery of immune cells and mediators to sites of infection or injury. Its transport functions also ensure the availability of essential nutrients and micronutrients (e.g., zinc, fatty acids) required for optimal immune cell proliferation and function (Gounden & Vashisht, 2023).

• Wound Healing: Albumin’s role in transporting nutrients, growth factors, and metal ions, combined with its antioxidant and anti-inflammatory properties, makes it indispensable for effective wound healing and tissue repair. Optimal albumin levels support collagen synthesis, angiogenesis, and immune cell recruitment necessary for successful wound closure (Linkous et al., 2018).

2.5 Buffering Capacity

Albumin contributes significantly to the maintenance of acid-base balance in the blood. Due to its numerous ionizable amino acid residues, particularly histidine residues, and its high concentration, albumin acts as a major non-bicarbonate buffer in plasma (Peters, 1996). It can accept or donate protons (H+ ions) to counteract changes in blood pH, helping to stabilize the internal environment. Its buffering capacity is particularly important in conditions of metabolic acidosis, where it helps to bind excess acid, thereby preventing drastic drops in pH that could compromise enzymatic function and cellular integrity.

2.6 Nutritional Role and Amino Acid Reservoir

While not its primary function, albumin can serve as a labile amino acid reservoir (Fan et al., 2021). In states of severe malnutrition or prolonged catabolic stress (e.g., severe injury, sepsis), albumin can be broken down to provide amino acids for protein synthesis in other vital tissues. However, this is a relatively inefficient and late-stage mechanism. More importantly, stable albumin levels reflect adequate protein intake and anabolic processes, indicating a robust nutritional state necessary for overall physiological function and recovery from illness or injury.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

3. Serum Albumin as a Biomarker

Given its multifaceted physiological roles and dynamic interplay with various metabolic and inflammatory pathways, serum albumin serves as a powerful and widely utilized biomarker in clinical practice. Its levels can provide a holistic snapshot of an individual’s nutritional status, hepatic function, inflammatory state, and overall physiological resilience, offering valuable prognostic information in a wide range of clinical settings.

3.1 Nutritional Status

Hypoalbuminemia, conventionally defined as a serum albumin concentration below 35 g/L, is frequently associated with malnutrition (Foss & Doblmeier, 2022). Inadequate dietary protein intake, malabsorption syndromes (e.g., inflammatory bowel disease, short bowel syndrome), and chronic diseases that increase metabolic demand or nutrient loss can all contribute to reduced albumin synthesis. In geriatric patients, chronic malnutrition is highly prevalent, often due to factors such as reduced appetite (anorexia of aging), dental problems, dysphagia, social isolation, economic hardship, and polypharmacy. While albumin has a relatively long half-life, making it a less sensitive indicator of acute nutritional changes compared to prealbumin or transferrin, persistently low albumin levels are a robust indicator of chronic protein-energy malnutrition (PEM) or significant chronic catabolic states (Gibbs et al., 2008). Therefore, hypoalbuminemia should prompt a thorough nutritional assessment and consideration of dietary interventions.

3.2 Liver Function

As the liver is the sole site of albumin synthesis, serum albumin levels are a direct reflection of hepatic synthetic function (Roche & Rondepierre, 2012). In conditions of chronic liver disease, such as cirrhosis, or in acute severe liver failure, hepatocyte damage and impaired synthetic capacity lead to significantly reduced albumin production, resulting in hypoalbuminemia. Consequently, serum albumin is often included as a component of liver function panels and is a key parameter in prognostic scoring systems for liver disease severity, such as the Child-Pugh score (Pugh et al., 1973). However, it is important to note that normal albumin levels do not necessarily rule out early-stage liver disease, as the liver has considerable synthetic reserve, and other factors (like inflammation) can influence albumin levels independently of liver function.

3.3 Inflammatory State

Serum albumin is a classic negative acute-phase reactant. This means that its concentration decreases significantly during systemic inflammation, infection, or acute stress (Gabay & Kushner, 1999). This decline is orchestrated by a complex interplay of mechanisms:

• Cytokine-Mediated Suppression: Pro-inflammatory cytokines, particularly interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), which are released during acute phase responses, directly inhibit albumin gene transcription and synthesis in hepatocytes (Peters, 1996).

• Increased Capillary Permeability: Inflammation leads to increased vascular permeability, allowing albumin to extravasate from the intravascular space into the interstitial fluid, particularly at sites of inflammation (Levick & Michel, 2010). This redistribution contributes to a lower circulating concentration.

• Increased Catabolism: In severe inflammatory states, there can be an increased rate of albumin breakdown or degradation.

The decrease in albumin during inflammation serves a protective role by allowing other acute-phase proteins (positive acute-phase reactants like C-reactive protein, fibrinogen) to increase, which are crucial for immune defense and tissue repair. However, sustained hypoalbuminemia due to chronic inflammation can perpetuate a vicious cycle of poor outcomes (Gibbs et al., 2008).

3.4 Physiological Resilience and Prognostic Indicator

Beyond specific organ function or nutritional status, serum albumin levels are increasingly recognized as a general indicator of an individual’s overall physiological resilience and capacity to withstand stress (Foss & Doblmeier, 2022). Low albumin levels are consistently associated with increased morbidity and mortality across a broad spectrum of medical and surgical conditions, including critical illness, sepsis, heart failure, chronic kidney disease, and cancer (Fan et al., 2021). It reflects a state of diminished physiological reserve, increased systemic inflammation, and compromised metabolic integrity. Thus, hypoalbuminemia serves as a powerful prognostic marker, identifying patients at higher risk for adverse events, prolonged hospitalization, and poorer recovery trajectories. This predictive utility makes it a valuable tool for risk stratification in various clinical populations.

3.5 Renal Function

While albumin is synthesized in the liver, its levels can also be significantly affected by renal function, particularly in conditions where there is excessive urinary loss of protein (proteinuria). In nephrotic syndrome, for instance, damage to the glomerular filtration barrier leads to the loss of large amounts of albumin into the urine, resulting in severe hypoalbuminemia (Dickerson, 2011). Similarly, in end-stage renal disease, chronic inflammation and malnutrition often contribute to reduced albumin levels. Therefore, interpreting serum albumin levels requires consideration of kidney function and potential protein loss.

3.6 Cardiac Function

Recent research has highlighted the prognostic significance of serum albumin levels in patients with cardiac conditions, particularly heart failure. Hypoalbuminemia in heart failure patients has been linked to increased mortality, hospital readmissions, and worse functional status (Yoshida et al., 2020). The mechanisms are multifactorial, including chronic inflammation associated with heart failure, malnutrition (cardiac cachexia), fluid overload (dilutional effect), and hepatic congestion leading to impaired albumin synthesis. Thus, albumin can serve as a useful adjunct biomarker in assessing the severity and prognosis of heart failure.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

4. Clinical Significance in Geriatric Hip Fracture Patients

Hip fractures represent a major public health concern, particularly in the elderly population. Annually, over 1.6 million hip fractures occur worldwide, with this number projected to rise significantly due to global demographic aging (International Osteoporosis Foundation, 2023). These injuries are devastating, leading to profound pain, immobility, loss of independence, and a significantly increased risk of morbidity and mortality. Surgical intervention, typically performed within 48 hours, is the standard of care, but elderly patients often present with complex comorbidities, making perioperative management challenging (Bonnaire & Weber, 2021).

In this highly vulnerable patient group, serum albumin has emerged as a consistently reliable and powerful prognostic indicator, providing critical insights into their capacity to withstand the stress of trauma and surgery, and predicting their recovery trajectory.

4.1 Prognostic Value

Numerous observational studies, meta-analyses, and systematic reviews have robustly demonstrated a strong inverse correlation between preoperative serum albumin levels and adverse outcomes in geriatric hip fracture patients. Hypoalbuminemia, often defined as a level below 3.5 g/dL (35 g/L), is consistently associated with:

• Increased Mortality: Patients presenting with hypoalbuminemia have significantly higher rates of in-hospital mortality, 30-day mortality, and one-year mortality following hip fracture surgery (Foss & Doblmeier, 2022; Gounden & Vashisht, 2023). Some studies report an increase in mortality risk by 2-5 times in severely hypoalbuminemic patients compared to those with normal levels (Wang et al., 2014). This association persists even after controlling for age, comorbidities, and fracture type, underscoring albumin’s independent prognostic value.

• Higher Incidence of Postoperative Complications: Hypoalbuminemia is a robust predictor of a wide array of postoperative complications, including:

  • Infections: Surgical site infections, pneumonia, urinary tract infections, and sepsis are considerably more frequent in patients with low albumin (Yang et al., 2020). Compromised immune function, delayed wound healing, and impaired antioxidant defenses contribute to this increased susceptibility.
  • Pressure Ulcers (Bedsores): Malnutrition and poor tissue perfusion, both linked to low albumin, contribute to skin breakdown and the development of pressure injuries, which are difficult to treat and prolong hospital stays (Linkous et al., 2018).
  • Delayed Wound Healing: Impaired protein synthesis and nutrient transport due to hypoalbuminemia lead to delayed incision healing, increasing the risk of wound dehiscence and infection.
  • Prolonged Hospital Stay and Rehabilitation: Patients with hypoalbuminemia typically experience longer inpatient stays, require more extensive rehabilitation, and have a reduced likelihood of returning to their pre-fracture functional status and home environment (Zou et al., 2021). This translates into higher healthcare costs and a greater burden on healthcare systems.
  • Cardiovascular and Pulmonary Complications: Increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), cardiac events (e.g., myocardial infarction, heart failure exacerbation), and respiratory complications (e.g., acute respiratory distress syndrome) due to fluid shifts, systemic inflammation, and impaired physiological reserve (Foss & Doblmeier, 2022).

4.2 Mechanisms Underlying the Association

The strong association between hypoalbuminemia and adverse outcomes in hip fracture patients is not merely correlative; it is underpinned by several interconnected pathophysiological mechanisms that compromise the patient’s ability to cope with the trauma, surgery, and recovery process:

• Exacerbated Malnutrition and Catabolism: Hip fracture itself is a highly catabolic event, triggering a robust inflammatory response that increases metabolic demands and protein breakdown. Pre-existing malnutrition, common in the elderly, is worsened by reduced oral intake due to pain, nausea, and NPO (nil per os) orders pre- and post-surgery (Gibbs et al., 2008). Hypoalbuminemia reflects this cumulative nutritional deficit and ongoing catabolism, indicating insufficient building blocks for tissue repair and immune function.

• Compromised Immune Function: As a key component of immune support, reduced albumin levels directly impair the host’s defense mechanisms. Lower antioxidant capacity weakens protection against oxidative stress generated during trauma and inflammation. Impaired transport of essential nutrients and immune modulators hinders immune cell proliferation, phagocytic activity, and antibody production (Fan et al., 2021). This leads to an increased susceptibility to opportunistic infections, which are a leading cause of morbidity and mortality in this patient group.

• Impaired Wound Healing and Tissue Repair: Albumin is crucial for providing amino acids, transporting growth factors, and maintaining the necessary osmotic gradient for nutrient delivery to the wound site. Hypoalbuminemia compromises collagen synthesis, fibroblast proliferation, and angiogenesis, all vital for effective wound healing (Linkous et al., 2018). Delayed or non-healing wounds increase the risk of infection and prolong recovery.

• Fluid Imbalance and Edema: Low oncotic pressure due to hypoalbuminemia results in fluid extravasation from the intravascular space into the interstitial tissues, leading to generalized edema (Michel & Neal, 1999). Edema at the surgical site can delay healing, increase susceptibility to infection, and impair local tissue oxygenation. Systemic edema can also contribute to pulmonary congestion, impaired organ function, and increased risk of complications like compartment syndrome in severe cases.

• Altered Pharmacokinetics of Medications: Many drugs commonly used in hip fracture patients (e.g., analgesics, antibiotics, sedatives) are highly protein-bound (Bouchard et al., 2013). In hypoalbuminemic patients, the unbound (active) fraction of these drugs can be significantly higher, leading to increased therapeutic effects, or more dangerously, heightened toxicity at conventional dosages. This necessitates careful drug dosing adjustments and vigilant monitoring to avoid adverse drug reactions.

• Inflammation and Systemic Inflammatory Response Syndrome (SIRS): Hip fracture trauma itself triggers a significant systemic inflammatory response. Hypoalbuminemia, as a negative acute-phase reactant, reflects the severity of this inflammatory burden (Gabay & Kushner, 1999). Persistent and exaggerated inflammation can lead to organ dysfunction, sepsis, and a higher risk of multi-organ failure. The reduced antioxidant capacity of low albumin further exacerbates oxidative damage during inflammation.

• Exacerbation of Frailty: Hypoalbuminemia is itself a component of frailty indices and contributes to the overall concept of physiological frailty in older adults (Fried et al., 2001). Patients with low albumin often exhibit reduced muscle mass (sarcopenia), decreased strength, poor mobility, and a diminished capacity to recover from physiological insults, making them inherently more vulnerable to complications following a hip fracture.

4.3 Clinical Implications and Management Strategies

The profound prognostic implications of serum albumin in geriatric hip fracture patients underscore its critical role in clinical management. Recognizing and addressing hypoalbuminemia can significantly impact patient outcomes.

• Risk Stratification and Preoperative Assessment: Serum albumin levels should be routinely measured during the preoperative assessment of all geriatric hip fracture patients (Foss & Doblmeier, 2022). A baseline albumin level provides valuable information for identifying patients at high risk for adverse postoperative outcomes, allowing for proactive intervention and more intensive monitoring. It can be integrated into comprehensive geriatric assessment tools and risk prediction scores.

• Nutritional Interventions: Given the strong link between hypoalbuminemia and malnutrition, nutritional optimization is paramount. While acute albumin infusions generally do not correct chronic malnutrition (see below), targeted nutritional support is crucial:

  • Preoperative Nutritional Support: For elective surgeries, or if time permits in hip fracture cases (e.g., stable patients awaiting surgery), a period of preoperative nutritional optimization (oral nutritional supplements, enteral feeding, or even parenteral nutrition in severe cases) can improve albumin levels and reduce complications (Zou et al., 2021). However, in urgent hip fracture surgery, this is often not feasible.
  • Perioperative and Postoperative Nutritional Support: Aggressive nutritional support should be initiated early in the postoperative period. This includes high-protein, high-calorie diets, oral nutritional supplements, and consideration of enteral or parenteral nutrition if oral intake is inadequate. The goal is to provide sufficient protein and energy to counteract the catabolic state and support endogenous albumin synthesis and tissue repair (Linkous et al., 2018).
  • Micronutrient Supplementation: Ensuring adequate intake of vitamins (especially A, C, D) and trace elements (e.g., zinc, selenium) that are crucial for immune function and wound healing is also important, as deficiencies often coexist with protein-energy malnutrition.

• Inflammation Management: Identifying and managing sources of systemic inflammation is crucial. This involves aggressive treatment of infections, optimal pain control, and early mobilization to reduce inflammatory mediators. However, directly manipulating albumin levels by suppressing inflammation remains a complex challenge.

• Fluid Management: Careful fluid management is essential to balance adequate hydration and perfusion with avoiding fluid overload and exacerbating edema (Michel & Neal, 1999). Hypoalbuminemic patients are more prone to edema; thus, judicious use of crystalloids and consideration of albumin solutions (where appropriate) are vital.

• Judicious Use of Albumin Infusion: The role of exogenous albumin infusion in non-cirrhotic hypoalbuminemic patients remains controversial and should be reserved for specific indications. While it can transiently increase plasma oncotic pressure and expand intravascular volume, it generally does not improve long-term nutritional status or consistently reduce mortality in critically ill patients unless there’s a specific indication such as large volume paracentesis, severe burns, or refractory septic shock (Caironi et al., 2014; Finnerty & Petersen, 2021). In the context of hip fracture, its routine use solely for correcting hypoalbuminemia is not supported by strong evidence (Foss & Doblmeier, 2022). However, it may be considered in patients with severe hypoalbuminemia (e.g., <2.5 g/dL) accompanied by significant edema causing organ dysfunction or refractory hypotension, though this must be weighed against potential risks like fluid overload and allergic reactions.

• Multidisciplinary Approach: Optimal care for geriatric hip fracture patients with hypoalbuminemia necessitates a multidisciplinary approach involving orthopedic surgeons, geriatricians, intensivists, nutritionists, physiotherapists, and nursing staff (Bonnaire & Weber, 2021). Coordinated care ensures comprehensive assessment, individualized nutritional plans, prompt management of complications, and tailored rehabilitation strategies.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

5. Conclusion

Serum albumin, far exceeding its simplistic definition as a mere plasma protein, is an extraordinarily versatile and indispensable molecule integral to maintaining a wide array of physiological processes essential for human health and survival. Its profound functions encompass the meticulous regulation of oncotic pressure, the ubiquitous transport of myriad endogenous and exogenous substances, the sophisticated orchestration of antioxidant defense mechanisms, and the crucial support of immune system integrity and inflammatory modulation. As a dynamic biomarker, its levels offer an unparalleled window into an individual’s intricate physiological landscape, reflecting not only nutritional status and hepatic synthetic capacity but also the systemic inflammatory burden and underlying physiological resilience.

In the critically vulnerable population of geriatric hip fracture patients, serum albumin levels transcend their role as a mere diagnostic marker, emerging as a paramount prognostic indicator. Low albumin levels are consistently and robustly associated with significantly increased mortality, a heightened incidence of severe postoperative complications including infections and delayed wound healing, prolonged hospitalizations, and poorer functional outcomes. These adverse associations are rooted in complex pathophysiological mechanisms, including exacerbated malnutrition, compromised immune function, impaired tissue repair, fluid imbalances, altered drug pharmacokinetics, and a general exacerbation of systemic frailty.

Therefore, a comprehensive understanding of serum albumin’s multifaceted roles and its specific clinical implications in geriatric hip fracture patients is not merely academic but profoundly practical. Routine measurement of serum albumin during preoperative assessment should be an integral part of risk stratification protocols. Furthermore, aggressive and individualized nutritional support, vigilant management of inflammation, judicious fluid management, and a holistic, multidisciplinary approach to care are indispensable for mitigating the risks associated with hypoalbuminemia and optimizing patient outcomes. Future research should continue to explore innovative therapeutic strategies aimed at not only correcting albumin deficiencies but also addressing the underlying causes of hypoalbuminemia and enhancing the overall physiological resilience of this fragile patient population.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

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