Assessment of Protein Status

Assessment of Protein Status
FCSN 442 - Nutrition Assessment Laboratory
By:Dr. David L. Gee
Central Washington University

Assessment of Protein Status
* Anthropometric Assessment
o body composition estimations
o midarm muscle circumference/area
* Laboratory Assessment
o serum albumin
o other serum proteins (transferrin, prealbumin, retinol-binding protein)
o urinary creatinine excretion
o total lymphocyte count

Midarm Muscle Area
* Estimate of MAMA is an estimate of overall muscle mass
* Assumptions

Midarm Muscle Circumference
* MAMC = AC - (.314 x TSF)

* “…change in arm muscle area is greater than the change in mid-arm circumference. Consequently, changes in upper-arm musculature are not as easily detected by measurement of mid-arm circumference as by AMA. Therefore, AMA is the preferred nutritional index.”

Arm Muscle Area
* AMA = ((MAC - (3.14 x TSF)2 ) / (4 x 3.14)
* adjusted AMA

Guidelines for Interpreting Percentile Values for Arm Muscle Area (appendix R)
Biochemical Assessment of Protein Status
* Two protein compartment model
* “No single test or group of tests can be recommended at this time as a routine and reliable indicator of protein status.” Young, 1990
* “…a combination of measures can produce a more complete picture of protein status.”

Serum Albumin
* Major serum protein
* Most common indicator of depleted protein status
* Half life = 14-20 days
* poor indicator of early protein depletion and repletion
* Levels affected by rate of synthesis (liver disease may reduce levels)
* May reflect level of physiological stress
* Levels affected by abnormal losses
* Levels affected by fluid status
* Normal values: 4.5 g/dL + 35-50 (SD)

Serum Transferrin
* Function: transport protein for iron
* half-life = 8-9 days
* Influenced by other factors
* limited usefulness in protein status assess.

Serum Prealbumin
* aka. transthyretin and thyroxine-binding prealbumin
* functions:
* short half life (2-3d), small body pool
* Returns to normal at beginning of nutritional therapy
* Influenced by other factors
* generally considered preferable than albumin and transferrin

Retinol Binding Protein
* Function: carrier for retinol
* responds like prealbumin
* very rapid turnover (12 hours), very small body pool
* generally not considered to be more useful than prealbumin

Immunocompetence
* Immune system affected by nutritional status
* Tests of immunocompetence useful functional indicators of nutritional status
* Delayed Cutaneous Hypersensitivty (DCH)
o intradermal injection of antigens
* Total Lymphocyte Count (TLC)

Total Lympocyte Count
* White blood cell count
* TLC = (%lymp x WBC)x100
* Normal = 1200-1800 cells/mm3
* Moderate PCM = 800-1200
* Severe PCM = < 800 Urinary Creatinine Excretion * Creatinine excreted in proportion to muscle mass * LBM estimated by comparing 24-hr urine creatinine excretion with standard based on stature or reference values of 23 and 18 mg/kg for M and F Example: Creatinine Height Index * CHI = (24 hr urine creatinine x 100) / (expected 24 hr urine creatinine for height) o CHI = 1436/1596 x 100 = 90% * expected values in table 9-1 (p306) o CHI > 80% = normal
o CHI = 60-80% = mild protein depletion
o CHI = 40-60% = moderate depletion
o CHI < 40% = severe depletion Assessment of Protein Status

Read more...

Immune System Overview Mechanisms of Immunosuppression

Immune System Overview Mechanisms of Immunosuppression
By:Bob Luebke
Immunotoxicology Branch
Experimental Toxicology Division
NHEERL, ORD

Role of the Immune System in Homeostasis

* Bidirectional interaction with other systems
o Reproduction
o Endocrine
o CNS

Basics of Immunology
The Immune Response
Innate Immunity
Adaptive (Acquired) Immunity
-Phylogenetically ancient
-Limited recognition
-Rapid (minutes – hours)
- No cell proliferation required
-Limited memory (? mammals)
-First appeared in jawed fishes
- Infinite array of specificities
- Slow (days)
-Requires proliferation and differentiation
-Long-lasting memory

Basics of Immunology
* The adaptive immune response to antigen
Organs of the Immune System
Immune System Anatomy
Organs of the Immune System
Thymus: source of naive T cells
Fate of T Cells in the Thymus
Positive selection: optimal binding to self Ag prevents apoptosis
Negative selection: superoptimal binding to self Ag induces apoptosis
B cells: Tolerance to “Self”
Anergy: low expression of
IgM on surface; can’t bind Ag
Clonal ignorance: too few
copies of Ag in the periphery

Thymus size and architecture:
* May be very sensitive to xenobiotics
* Also sensitive to acute toxicity

Methods for Assessing Direct Immunotoxicity Associated with Exposure to Chemicals
Organs of the Immune System
Spleen: Antigen trapping and presentation, clonal expansion, cellular export
Organs of the Immune System
Lymph nodes: Antigen trapping and presentation, clonal expansion, cellular export
Cells of the Immune System
Innate Immune System: Granulocytes
Neutrophil (“PMN”)
* First responders
* Phagocytosis and killing of bacteria
* Inflammation

Eosinophil
* Allergy
* Killing parasite larvae
Basophil
* Circulating mast cells
* Allergy/anaphylaxis

Innate Immune System: Granulocytes
Neutrophil (“PMN”)
* First responders
* Phagocytosis and killing of bacteria
* Inflammation
Cells of the Immune System
Innate Immune System: Monocytes
Monocyte/macrophage
Macrophage with ingested
asbestos fiber (encarta.msn.com)
* Phagocytosis and killing of bacteria
* Antigen processing
* Inflammation
Adaptive Immune System: Lymphocytes
Activated B cell
Peripheral blood
Activated T cell (SEM)
* B cells: Mature into plasma cells, secrete antibody (IgM, IgG, IgA, IgE, IgD)
* T cells: T helper - produce stimulatory and regulatory cytokines
* T cells: T cytotoxic/suppressor – contact-dependent cytotoxicity,

regulation of immune response
* NK cells: direct killing of cells (innate arm of IS)

Plasma Cells Produce Antibodies
* IgM: Primary response, efficient agglutination
* IgG: Recall response, highest concentration
* IgA: Mucosal surfaces, trapping of microbes
* IgE: Allery/anaphylaxis

Factors Affecting Immunocompetence
* Age
* Gender
* Genotype
* Nutritional status
* Life style choices
* Acute toxicity
CONCEPT: Individual immunocompetence, in the absence of xenobiotic exposure, is complex, dynamic and affected by fixed and variable factors. At the population level, the “normal” range is broad.

Immunocompetence in the Young: Innate immunity
* Neutrophils
* NK cells
Immunocompetence in the Young: Adaptive immunity
* Humoral immunity
* Cellular immunity
* Resistance to infection
Advanced Age and Immunocompetence

* Innate Immunity
* Adaptive immunity
* Resistance to infection

Gender and Immunocompetence
Genotype and Immunocompetence
Lifestyle and Immunocompetence
* Recreational drug use
* Excessive use of alcohol
* Smoking
* Stress

Xenobiotic Exposure and Immunocompetence
Immune
System
Exposure
Suppression
Infection
Neoplasia
Modulation
Allergy
Autoimmunity

Consequences of Xenobiotic Exposure on Immunocompetence
“Pre-immune” Mechanisms of Defense
Immune Mediated Resistance to Infection
Organism Factors Influencing Host Resistance
Mechanisms of Chemically-induced Immunosuppression
Mechanisms of Suppression:
Effects on Supply of Cells
Mechanisms of Suppression: Effects on Supply of Cells
UVB (320-280 nm) exposure
Mechanisms of Suppression: Tolerance Induction (and then some)
Mechanisms of Suppression: Tolerance Induction (human studies)
Mechanisms of Suppression: Modulation of cytokine production
Mechanisms of Suppression: Th1/Th2 Polarization
Mechanisms of Suppression: Disruption of innate immunity
Human and Mouse Macrophage Responses to Ozone in vivo
Mechanisms of Chemically-induced Immunosuppression
Mechanisms of Suppression:
Summary
* Reduced supply of immune system cells
* Misdirection of the immune system
* Direct effects on cells
* Combination of effects
Decreased Host Resistance: Implications for Human Health

Immune System Overview Mechanisms of Immunosuppression

Read more...

Metabolic Disorders - Inborn Errors of Metabolism

Metabolic Disorders - Inborn Errors of Metabolism
By:Dr. Sara Mitchell

Overview
* Proteins - what are they and what do they do?
* Amino Acids - what are they and what do they do?

Eight Essential Amino Acids
* Tryptophan
* Lysine
* Methionine
* Phenylaline
* Theronine
* Valine
* Leucine
* Isolecucine

Inborn Errors of metabolism
* Affects amino acid & protein, carbohydrate, and lipid metabolism.
* Most disorders are autosomal recessive in transmission
* Most disorders are evident at or soon after birth.
* Early detection and treatment are essential to the prevention of irreversible cognitive impairment and early death

Newborn Screening: What is it?
* A test developed in 1961 by Dr. Robert Guthrie to evaluate infants for certain genetic anomalies, inborn errors of metabolism, and other disorders.

http://health.state.ga.us/programs/nsmscd/

Phenylketonuria (PKU):What is it?
* The most common amino acidemia. Classic PKU develops in the absence of the enzyme phenylalanine hydroxylase.
* Incidence

Phenylketonuria: How’s it happen?
* Cause
o absent Phenylalanine hydroxylase causes a build up phenylalanine
* Effect

Phenylketonuria
* Treatment
* Prognosis

Galactocemia: What is it?
* An inborn error of carbohydrate metabolism in which the hepatic enzyme galactose 1-phosphate uridine transferase is absent.
* Incidence

Galactocemia: How does it happen?
Galactocemia: What are the clinical manifestations?
Galactocemia: Diagnosis & Treatment
* Diagnosis
* Treatment

Metabolic Disorders - Inborn Errors of Metabolism.ppt

Read more...