Hypoalbumin; independent

risk factor for severity and

mortality affects
Hendri pangestu
HYPOALBUMINEMIA

▪ A LOW LEVEL OF ALBUMIN IN THE BLOOD

▪ NORMAL RANGE: 3,5 – 5,5 g/ dl
TABLE OF CONTENTS
01 02 05
WHAT DOES ALBUMIN DO? CAUSE OF HYPOALBUMINEMIA REFERENCE

03 04
CLINICAL FEATURES
DIAGNOSIS + TREATMENT
 01
WHAT DOES
ALBUMIN DO?
 THE MOST ABUDANT PROTEIN IN THE BLOOD

1. MAINTAINS ONCOTIC PRESSURE

2. HYDROPHILIC → TRANSPORTS LIPOPHILIC MOLECULES
HORMONES, FATTY ACIDS, UNCONJUGATED BILIRUBIN
3. pH BUFFER
4. SCAVENGES REACTIVE OXYGEN SPECIES
5. BINDS CALCIUM AND DRUGS
 02
CAUSES OF
HYPOALBUMINEMIA
• IMPAIRED SYNTHESIS 1. LIVER DISEASE: CIRRHOSIS, CHRONIC
• INCREASED HEPATITIS
UTILIZATION - IMPAIRED SYNTHESIS
• DISTRIBUTION
PROBLEMS
- CAPILLARY LEAKAGE → DISTRIBUTION
• EXCESSIVE LOSS PROBLEM
2. KIDNEY DISEASE:
NEPHROTIC SYNDROME: ≥ 3 g/ day protein
loss
CHRONIC KIDNEY DISEASE: SLOWER
LOSS
• IMPAIRED SYNTHESIS 3. MALNUTRITION/ MALABSORPTION
• INCREASED - SEVERE MALNUTRITION →
UTILIZATION KWASHIORKORMILD MALNUTRITION IN
• DISTRIBUTION ELDERLY
PROBLEMS - MALABSORPTION
• EXCESSIVE LOSS ULCERATIVE COLITIS, CROHN’S, CELIAC’S
4. INFLAMATION:
- NEGATIVE PHASE REACTANT → LEVELS
DECREASE WITH INFLAMMATION
THEREFORE NOT A GOOD MARKER OF
MALNUTRITION
- IL-6, TNF → CAPILLARY LEAKAGE
INCREASED DEGRADATION
DECREASED SYNTHESIS
- SEPSIS, SEPTIC SHOCK
 03

CLINICAL FEATURES
DEPEND ON UNDERLYING CAUSE

1. WEAKNESS
2. PERIPHERAL EDEMA/ SWELLING
3. ASCITES
4. THIN HAIR
5. JAUNDICE
 04
DIAGNOSIS +
TREATMENT
IDENTIFY CAUSE:
SUSPICION
LIVER DISEASE → TEST: LIVER FUNCTION TESTS (LFT₁) →AST, ALT,
ALP, ɣGT, BILIRUBIN, ALBUMIN
NEPHROTIC SYNDROME→ TEST: URINE ALBUMIN/ PROTEIN
PROTEIN LOSING ENTEROPATHY → TEST: STOOL α1 ANTI TRYPSIN

TREATMENT:
TREAT UNDERLYING CAUSE
ALBUMIN INFUSION, (ORAL?)
 ALBUMIN
▪ Most abundant protein : (55 – 60%)
▪ It has one polypetide chain with 585 amino acids.
It has a molecular weight of 69000 D
▪ It is synthesized by hepatocytes, therefore
estimation of albumin is a liver function test
▪ Half life of albumin is about 20 days
Physiological effect of exogenous albumin
 FUNCTIONS OF ALBUMIN
1. COLLOID OSMOTIC PRESSURE OF PLASMA
● The total osmolality of serum is 278 – 305
mosmol/ kg (about 5000 mmHg). But this is
exerted mainly by salts, which can pass easily
from intravascular to extravascular space.
● So, the osmotic pressure exerted by
electrolytes inside and outside the vascular
compartments will cancel each other.
● If protein concentration in serum is reduced,
the EOP is correspondingly decreased. Then
return of water into blood vessels is
diminished, leading to accumulation of water
in tissues. This is called edema.
● Edema is seen in condition where albumin
level in blood is less than 2 g/ dl
Oncotic pressure is a part of the osmotic pressure, particularly in biological fluids such as
plasma. Oncotic pressure is exerted by colloids or, in other words, proteinaceous
macromolecules of the plasma like albumin, globulin, and fibrinogen. Oncotic pressure is
therefore also called ‘colloid osmotic pressure.’ Albumin is the most abundant of all three
2. TRANSPORT FUNCTION
● Albumin is the carrier of various hydrophobic
substances in the blood. Being a watery medium,
blood cannot solubilize lipid components.
● Bilirubin and non esterified fatty acids are specifically
transported by albumin.
● Drugs like aspirin, salicylate, phenytoin; Hormones like
thyroxine, steroid hormones; Metals like calcium,
copper and heavy metals are carried by albumin. Only
the unbound fraction drugs is biologically active.
3. BUFFERING ACTION
● All proteins have buffering capacity
● Because of its high concentration in blood, albumin
has maximum buffering capacity.
● Albumin has a total of 16 histidine residues which
contribute to this buffering action.
4. NUTRITIONAL FUNCTION

● All tissues cells can take up albumin by pinocytosis.

It is then broken down to amino acid level.
● So, albumin may be considered as the transport form
of essential amino acids from liver to extrahepatic
cells.
 05

REFERENCE
Albumin solutions have been used worldwide for the treatment of critically ill patients since they became
commercially available in the 1940s.
However, their use has become the subject of criticism and debate in more recent years.
Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies
have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of
patients are most likely to benefit from their use.
However, many questions remain related to where exactly albumin fits within our fluid choices.
Albumin administration, although unlikely to cause harm in most
patients, is not necessary in all critically ill patients and should be
reserved for use in specific groups of patients in whom there is
evidence of benefit.

There is now enough evidence – albeit largely from subgroup

analyses – and plausible biological rationale to support use of
albumin in patients with septic shock when a colloid is
considered.

Albumin administration should be considered in patients with

cirrhosis and spontaneous bacterial peritonitis, but possibly also
other infections; in hypo oncotic patients with acute respiratory
distress syndrome; and also in patients with cirrhosis and type 1
hepatorenal syndrome.
Study Design: Retrospective cohort study.

American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2011
to 2014.
identified 1498 adult patients in the ACS-NSQIP database who underwent laminectomy and excision of
metastatic extradural spinal tumors. Patients were categorized into normo albuminemic and hypo albuminemic
(ie, albumin level <3.5 g/dL) groups.
Preoperative serum albumin levels of 1498 patients. The red line represents
the cutoff for hypoalbuminemia (ie, albumin 3.5 g/dL). The mean albumin
level was 3.66 g/dL with a standard deviation of 0.66 g/dL.
Hypoalbuminemia was present in 34.2% (512/1498) of patients.
Mild, 3.3 to 3.4 g/dL,
mild-moderate, 3.1 to 3.2 g/dL,
moderate-severe, and 2.8 to 3.0 g/dL, and
severe hypoalbuminemia 1.2 to 2.7 g/dL,
respectively
were defined as a serum albumin level of
Results:
Hypoalbuminemia was associated with increased risk of perioperative mortality,
any complication, sepsis, intra- or postoperative transfusion, prolonged
hospitalization, and non-home discharge.
However, albumin depletion was also associated with decreased risk of
readmission. There was an albumin level–dependent effect of increasing
mortality and complication rates with worsening albumin depletion.

Conclusions:
Hypoalbuminemia is an independent risk factor for perioperative mortality and
morbidity following surgical decompression of metastatic spinal tumors with a
dose-dependent effect on mortality and complication rates. Therefore, it is
important to address malnutrition and optimize nutritional status prior to
surgery.

Global Spine Journal 2019, Vol. 9(3) 321-330 ª The Author(s) 2018 Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/2192568218797095 journals.sagepub.com/home/gsj
Latar belakang: Hipoalbuminemia pada pasien rawat inap berkaitan dengan prognosis buruk pasien. Penelitian ini,
mengidentifikasi bahwa hipoalbuminemia berat pada awal pasien masuk rawat inap sebagai prediktor andalan
penanda laboratorium dalam mortalitas.
Of the 747 hypoalbuminemia in hospitalized patients

Most patients (83.4 %) had less than or equal to 2.5 g/dL albumin level (severe hypoalbuminemia);

16.6 percent had over 2.5 g/dL to 3.5 g/dL (mild – moderate hypoalbuminemia).

The underlying condition of severe hypoalbuminemia patients was HIV/AIDS infection (29.9 %) and
sepsis (24.6 %).

DISCUSSION

The cause of hypoalbuminemia in sepsis patients are often multifactorial, such as decreased
albumin synthesis, increased albumin loss, redistribution of albumin to locations outside the
intravascular space, and dilution of albumin within the intravascular space.
In addition, some drugs, including antibiotics, can bind with plasma protein and form protein-
drug complexes. Binding to plasma proteins plays a major role in drug treatment.5 However,
severe hypoalbuminemia may result in potentially life-threatening consequences.
The most important concept in treating hypoalbuminemia patients is to address the underlying
problem.
The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a
30% mortality rate.

We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum
albumin in AP.
Data from 2461 patients were extracted from the international, prospective, multi centre AP registry
operated by the Hungarian Pancreatic Study Group.

Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during
hospitalization (n = 1272) were analysed.

The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization.
Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and
organ failure and is associated with longer hospital stay.

Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a
dose-dependent relationship with local complications, organ failure and length of stay.
Free radicals are highly reactive molecules produced as the result of normal cellular
oxygen metabolism in mammals.
At low or moderate levels free radicals exert beneficial effects on cellular responses and
immune function whereas at high concentrations, they generate oxidative stress, a
deleterious process that can damage all cell structures and cause the onset and/or
progression of a growing number of diseases.

Plasma, a body compartment known to be exposed to continuous oxidative stress,

contains a wide range of endogenous antioxidant species among which albumin
represents the most abundant and important.
Therefore, human serum albumin (HSA) used as a resuscitation fluid could represent an
opportunity to enhance endogenous antioxidant protection in critical pathological
interventions.
HSA infusion has been shown to allow for restoring thiol-radical deficient stock during
cirrhosis and improving thiol-dependent anti-oxidant protection.
Evaluation of the structural quality of human albumin preparations
Albumin binding cobalt assay
Evaluation of albumin glycation
UV/visible and fluorescence spectrometry of albumins

Evaluation of the antioxidant capacity of human albumin preparations

Albumin controls
ORAC (Oxygen Radical Absorbance Capacity) assay
Quantification of free thiols using Ellman's reagent
Hydroxyl scavenging capacity of human albumin
Free radical-scavenging capacity of human albumin

The albumins from Octapharma (Albunorm®) and LFB (Viale Bex

® and Ydralbum®) showed a good batch-to-batch consistency
associated with a better antioxidant potential which was not
the case for all the other providers
Acute respiratory failure (ARF) is a life-threatening event, which is frequently associated with the
severe exacerbations of chronic obstructive pulmonary disease (COPD).
Hypoalbuminemia is associated with increased mortality in patients with COPD. However, to date,
little is known regarding whether or not hypoalbuminemia is a risk factor for developing ARF in
COPD.
Conclusion: Hypoalbuminemia is a strong risk factor for ARF in patients with COPD. Therefore, further
prospective studies are required to verify whether or not albumin supplementation or nutritional
support may help to reduce the risk of ARF in patients with COPD.
Study Design and Population
A prospective longitudinal cohort study was carried out at Trieste University hospital, Italy. All adult patients
(aged > 18 years) consecutively admitted to the Infectious Diseases Unit from March 2020 to June 2021
were considered for inclusion if affected by COVID-19 pneumonia.
Diagnosis of COVID-19 pneumonia included a Nucleic Acid Amplification Test positive for SARS-CoV-2 and
radiographic findings suggestive of pneumonia.
Patients without serum albumin determination at hospital admission and those who refused to participate
were excluded from the study.

During the study period, a total of 864 patients diagnosed with COVID-19 pneumonia were enrolled.

Almost a quarter of patients were obese, and more than half suffered from hypertension.
Hypoalbuminemia (SA < 3.5 g/dL) was detected in 586 patients (67.8%). The interval between symptoms
onset and hospitalization did not differ between patients presenting hypoalbuminemia at hospital
admission or not
Conclusions
Our study confirms that hypoalbuminemia at hospital admission may identify patients with
COVID-19 pneumonia at higher risk of severe respiratory failure, death, and longer LOS.
SA level of 3.2 g/dL was identified as the better cut off value to recognize patients at risk for
severe respiratory failure (IMV) and 90-day mortality.
Hypoalbuminemia reflects several pathological conditions, including nutritional deficiencies and chronic
inflammation.
However, its relationship with short-term and long-term mortality in patients undergoing continuous renal
replacement therapy (CRRT) remains unclear. The present study aimed to assess the effect of hypoalbuminemia
on mortality in a large cohort of patients undergoing CRRT.
The study retrospectively reviewed 1,581 patients who underwent CRRT for the treatment of acute kidney injury
from 2010 to 2016.
 Nonlinear relationship between the serum
albumin level and predicted probability of
all-cause mortality

Hypoalbuminemia is associated with increased morbidity and mortality in several

pathological conditions.
Despite the clinical implications of hypoalbuminemia, its relationship with mortality in
patients receiving CRRT has not been demonstrated. To our knowledge, the present study is
the first to show that hypoalbuminemia is associated with high mortality after CRRT initiation.
This trend was independent of the timeframe of follow-up or the location of death (intensive
care unit or hospital ward).
Emergency patients with hypoalbuminemia are known to have increased mortality.
No previous studies have, however, assessed the predictive value of low albumin on mortality in
unselected acutely admitted medical patients.
We aimed at assessing the predictive power of hypoalbuminemia on 30-day all-cause mortality in a
cohort of acutely admitted medical patients.
Malnutrition with hypoalbuminemia (albumin < 35 g/L) is an important factor in
predicting risks associated with colorectal cancer surgery.
However, there is limited data about the effects of mild hypoalbuminemia with
small decreases in albumin on postoperative complications.
Conclusions
In colorectal cancer patients, malnutrition with mild hypoalbuminemia is a
common problem and associated with more comorbidities.
After propensity score matching, a significant association with many
postoperative complications was demonstrated.
Randomized controlled trials are needed to evaluate if early identification
and aggressive nutritional intervention in patients with even mild
hypoalbuminemia would reduce the rate of postoperative complications and
improve postoperative outcomes.

In colorectal cancer, this is the first propensity score matching study of

malnutrition with mild hypoalbuminemia which demonstrates that a mild
decrease in serum albumin contributes significantly to poor postoperative
outcome.
In summary, HSA has been applied in clinical practice since
the 1940s. Because of its ability to regulate colloid osmotic
pressure, antioxidant properties, and its capacity to regulate
and buffer the concentration of nitric oxide, it is widely used
in treating critically ill patients nowadays.
THANKS!
Hydrophilic means water loving; hydrophobic means resistant to water