Transcript Dr.Noha El-Sharnouby

‫بسم هللا الرحمن الرحيم‬
By
Dr Noha M.
Elsharnouby
Lecturer
of Anesthesia and
intensive care and pain
management
Ain Shams university
 That nutrition and health are intimately
linked has been known since ancient times. It
is now essential to realize the vital importance
of micronutrients to health and that several
micronutrients have antioxidant roles.
What is the evidence in ICU?
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Early enteral feeding is best
Hyperglycaemia/overfeeding are bad
Nutritional deficit causes worse outcome
EN causes aspiration and VAP, while PN cause
infection
 EN and PN can be used to achieve goals
 Protocols improve delivery of feeding
 Some nutrients show promising results
Anti-oxidants
 Normal state: reduction > oxidation
 Acute stress: injury/sepsis causes acute dysregulation:
ROS/RNOS formed
 Mitochondria are both sources and targets
 Observational studies: anti-oxidant capacity inversely
correlated with disease severity due to depletion
during oxidative stress
Reactive Oxygen Species O-, NOPositive actions:
 Bactericidal
 Regulation of vascular
tone
 Cell signalling
But mostly detrimental:
Cell injury (ischaemia
/reperfusion)
 DNA, Lipids, Proteins
Organ dysfunction
 Lungs, Heart, Kidney
Liver, Blood, Brain
Inflammatory
mediators
Healing/repair/
defence
ROS/RNOS
Exacerbation of
cell and tissue
injury
Microneutrient
 Present in the body in amounts less than 50 ug
per gram of body tissues.
 Essential nutrients for an optimal functioning of
organs and tissues, including the immune system
and the heart.
 In hypermetabolic patients in the ICU the trace
element requirements may be far greater.
 Nine trace elements are required by humans in
small amounts : iron, iodine, fluorine, zinc,
chromium, selenium, manganese,
molybdenum, and copper.
 All trace minerals are toxic at high levels, and
some (arsenic, nickel, and chromium) have
been implicated in carcinogenesis.
 Except for deficiencies of iron, zinc, and
iodine, mineral deficiencies do not often
develop spontaneously in adults on ordinary
diets; however, infants are more vulnerable
because of their rapid growth and variation in
intake.
Selenium
 Humans and animals require selenium for
the function of a number of seleniumdependent enzymes, also known as
selenoproteins.
 Seleinum function involves
selenoproteins, glutathione peroxidases,
thioredoxin, and iodothyronine
deiodinases (thyroid hormone
deiodinases).
• Nutrient interactions:
 Selenium appears to support the activity of vitamin E
(a-tocopherol) in limiting the oxidation of lipids.
 Thioredoxin reductase also maintains the antioxidant
function of vitamin C by catalyzing its regeneration.
 Selenium deficiency may exacerbate the effects of
iodine deficiency.
 Deficiency:
 Muscular weakness, muscle wasting, and
cardiomyopathy
 down-regulation of the nuclear transcription factor kB,
• Disease Prevention
 Immune function stimulation: expression
of cell signaling molecules called cytokines,
which orchestrate the immune response,
selenium deficiency is associated with
impairment of both cell-mediated immunity
and B-cell function.
 Viral infection prevention
• Disease Prevention
 Cancer: increasing the levels of selenium
metabolites that inhibit tumor cell growth.
 Cardiovascular diseases: decrease the risk
of cardiovascular diseases by decreasing
lipid peroxidation and influencing the
metabolism of prostaglandins.
• Toxicity
 high doses can be toxic.
 Acute and fatal toxicities have occurred with accidental or
suicidal ingestion of gram quantities of selenium.
 Chronic selenium toxicity (selenosis) may occur with smaller
doses of selenium over long periods of time.
 symptoms of selenosis are hair and nail brittleness and
loss, gastrointestinal disturbances, skin rashes, a garlic
breath odor, fatigue, irritability, and nervous system
abnormalities.
 The Food and Nutrition Board (FNB) recently set the
tolerable upper level (UL) for selenium at 400 mcg/day in
adults based on the prevention chronic selenium toxicity.
• Drug Interactions
• At present the anticonvulsant medication,
valproic acid, has been found to decrease
plasma selenium levels.
• The Recommended Dietary
Allowance (RDA)
(55 mcg/day)
MOLYBDENUM
 function as a cofactor for three enzymes.
 Sulfite oxidase catalyzes the transformation of sulfite to
sulfate, a reaction that is necessary for the metabolism of
sulfur-containing amino acids, such as cysteine. crucial for
human health.
 Xanthine oxidase catalyzes the breakdown of nucleotides
(precursors to DNA and RNA) to form uric acid, which
contributes to the antioxidant capacity of the blood.
 Xanthine oxidase and aldehyde oxidase also play a role in the
metabolism of drugs and toxins.
Deficiency
 has never been observed in healthy people.
 The only documented case of acquired molybdenum
deficiency occurred in a patient with Crohn's disease on
long-term TPN without molybdenum added.
 The patient developed rapid heart and respiratory rates,
headache, night blindness, and ultimately became
comatose.
 The symptoms disappeared when the administration of
amino acid solutions was discontinued.
 Molybdenum supplementation (160 mcg/day) reversed
the amino acid intolerance and improved his clinical
condition.
The Recommended Dietary Allowance
(RDA)
 (45 mcg/day for adults) is sufficient to prevent deficiency.
And the tolerable upper intake level (UL) of 2,000 mcg/day
which should be safe for adults.
ZINC
 Zinc plays important roles in growth and development,
the immune response, neurological function, and
reproduction.
 On the cellular level, the function of zinc can be
divided into three categories: 1) catalytic, 2) structural,
and 3) regulatory.
 Catalytic role:
Nearly 100 different enzymes depend on zinc for their
ability to catalyze vital chemical reactions.
 Structural role:
Zinc plays an important role in the structure of proteins
and cell membranes. A finger-like structure, known as a
zinc finger motif, stabilizes the structure of a number of
proteins.
Loss of zinc from biological membranes increases their
susceptibility to oxidative damage and impairs their
function.
•Regulatory role:
•Regulate gene expression by acting as transcription
factors (binding to DNA and influencing the
transcription of specific genes).
•A role in cell signaling and has been found to influence
hormone release and nerve impulse transmission.
•A role in apoptosis , a critical cellular regulatory process
with implications for growth and development, as well as
a number of chronic diseases.
Nutrient Interactions:
 Copper: interfere with copper bioavailability
 Iron: Supplemental but not dietary levels of iron may
decrease zinc absorption.
 Calcium: Calcium in combination with phytic acid
reduces zinc absorption, and folic acid:
 Folate: the bioavailability of dietary folate is increased
by the action of a zinc-dependent enzyme.
Prevention of Diseases
 Impaired growth and development:
zinc availability affects cell signaling systems that
coordinate the response to the growth-regulating
hormone, insulin-like growth factor-1 (IGF-1)
 Impaired immune system function:
Increased susceptibility to infectious disease in
children
and elderly ( vulnerable to mild zinc deficiency)
Drug Interactions
 Certain antibiotics: as tetracyclines and
quinolones, may decrease absorption of the
antibiotic
 The therapeutic use of metal chelating
(binding) agents like: penicillamine (as in
Wilson's disease) has resulted in severe zinc
deficiency.
 Anticonvulsant drugs, especially sodium
valproate, may also precipitate zinc deficiency.
 Prolonged use of diuretics may increase
urinary zinc excretion
The Recommended Dietary Allowance
(RDA)
 The RDA for zinc (8 mg/day for adult women and 11
mg/day for adult men)
FLOURIDE (FLOURINE)
 occurs naturally in the Earth's crust, water, and
food as the negatively charged ion, fluoride (F-).
 About 95% of the total body fluoride is found in
bones and teeth.
 fluoride is not generally considered an essential
mineral element because humans do not require
it for growth or to sustain life.
• Nutrient Interactions:
Calcium and magnesium form insoluble complexes with
fluoride and significantly decreasing fluoride absorption
 Deficiency
An increased risk of dental caries for individuals of all ages.
 The Adequate Intake (AI):
0.05 mg/kg of body weight most effectively without causing
the unwanted side effect of tooth enamel mottling known as
dental fluorosis.
 Disease Prevention
Prevention of Dental caries , and osteoporosis.
Drug Interactions
Calcium supplements, as well as
calcium and aluminum containing
antacids, can decrease the
absorption of fluoride.
It is best to take these products 2
hours before or after fluoride
supplements
CHROMIUM
 The two most common forms of chromium are trivalent
chromium (III) and hexavalent chromium (VI)
 Recent research suggests that a low-molecular-weight
chromium-binding substance (LMWCr) may enhance the
response of the insulin receptor to insulin. The ability of the
LMWCr to activate the insulin receptor is dependent on its
chromium content.
 Nutrient Interactions:
Iron, Vitamin C, and Carbohydrates
 Deficiency:
Chromium deficiency was reported in patients on longterm intravenous feeding who did not receive
supplemental chromium in their intravenous solutions.
 These patients developed evidence of abnormal glucose
utilization and increased insulin requirements that
responded to chromium supplementation.
 chromium insufficiency has been hypothesized to be a
contributing factor to the development of Type 2
diabetes.
 The Adequate Intake (AI):
from 20 -30 mcg\day.
Disease Prevention
 Impaired glucose tolerance and type 2 (non-insulin
dependent) diabetes.
 Cardiovascular diseases:
Impaired glucose tolerance and type 2 diabetes are
associated with adverse changes in lipid profiles and
increased risk of cardiovascular diseases.
 Increases muscle mass:
Claims that chromium supplementation increases lean
body mass and decreases body fat are based on the
relationship between chromium and insulin action.
MANGANESE
The derivation of its name from the Greek word for magic
 Manganese (Mn) plays an important role in a number of
physiologic processes as a constituent of some enzymes
and as an activator of other enzymes
 Antioxidant function:
• Manganese superoxide dismutase (MnSOD) is the
principal antioxidant enzyme of mitochondria.
• MnSOD catalyzes the conversion of superoxide
radicals to hydrogen peroxide, which can be reduced
to water by other antioxidant enzymes.
 Metabolism:
A number of manganese-activated enzymes play
important roles in the metabolism of
carbohydrates, amino acids, and cholesterol.
 Pyruvate carboxylase, and phosphoenolpyruvate
carboxykinase (PEPCK), manganese-activated
enzymes, play critical roles in gluconeogenesis.
 Arginase, other manganese-containing enzyme,
is required by the liver for the urea cycle
• Bone development:
Manganese is the preferred cofactor of enzymes
called glycosyltransferases, which are required for
the synthesis of proteoglycans that are needed for
the formation of healthy cartilage and bone.
 Wound healing:
manganese is required for the activation of
prolidase, an enzyme that functions to provide
the amino acid, proline, for collagen formation in
human skin cells.
 Nutrient Interactions:
iron, magnesium and calcium.
 Drug Interactions:
Magnesium-containing antacids and laxatives
and the antibiotic medication, tetracycline, may
decrease the absorption of manganese .
 The adequate intake (AI)
2.3 mg/day for adult men and 1.8 mg/day for adult
women.
IRON
 In humans, iron is an essential component of hundreds
of proteins and enzymes.
 Oxygen transport and storage: Hemoglobin and
myoglobin
 Electron transport and energy metabolism:
Cytochromes are heme-containing compounds that are
critical to cellular energy production and therefore life,
through their roles in mitochondrial electron transport.
 Nonheme iron-containing enzymes, such as NADH
dehydrogenase and succinate dehydrogenase, are also
critical to energy metabolism.
 Antioxidant and beneficial pro-oxidant functions:
Catalase and peroxidases are heme-containing enzymes
that protect cells against the accumulation of hydrogen
peroxide, a potentially damaging reactive oxygen species.
 DNA synthesis:
Ribonucleotide reductase is an iron-dependent enzyme
that is required for DNA synthesis.
 Regulation of intracellular iron:
Iron response elements are short sequences of nucleotides found
in the messenger RNA (mRNA) that codes for key proteins in the
regulation of iron storage and metabolism.
 Oxygen sensing:
 Under hypoxic conditions transcription factors,
known as hypoxia inducible factors (HIF), bind to
response elements in genes that encode various
proteins involved in compensatory responses to
hypoxia and increase their synthesis.
 Recent research indicates that an iron-dependent
prolyl hydroxylase enzyme plays a critical role in
regulating HIF and consequently, physiologic
responses to hypoxia.
• Nutrient Interactions:
 Vitamin A: deficiency may exacerbate iron
deficiency anemia.
 Copper: Adequate copper nutritional status
appears to be necessary for normal iron
metabolism and red blood cell formation.
 Zinc: iron supplements can inhibit the
absorption of zinc.
 calcium: decrease the absorption of iron.
Disease Prevention
 Impaired intellectual development in children
 Lead toxicity:
Iron deficiency may increase the risk of lead poisoning in
children.
 Pregnancy complications:
severe anemia in pregnant women are associated with adverse
pregnancy outcomes.
 Impaired immune function:
Iron is required by most infectious agents, as well as by the
infected host in order to mount an effective immune response,
including the differentiation and proliferation of T lymphocytes
and the generation of reactive oxygen species (ROS), which are
used for killing pathogens.
Adverse Effects:
 At therapeutic levels for iron deficiency, iron
supplements may cause:
 gastrointestinal irritation
 nausea, and vomiting
 diarrhea, or constipation.
 Stools will often appear darker in color
Drug Interactions:
 Medications that decrease stomach acidity, such as
antacids, histamine (H2) receptor antagonists, and
proton pump inhibitors may impair iron absorption.
 Decreased absorption and efficacy of the medication:
levodopa, levothyroxine, methyldopa, penicillamine,
quinolones, tetracyclines, and bisphosphonates.
 Cholestyramine resin interferes with iron absorption.
The Linus Pauling Institute
Recommendation
 A multivitamin/multimineral supplement containing
100% of the daily value (DV) for iron provides 18 mg of
elemental iron.
COPPER
 An essential trace element.
 The ability of copper to easily accept and
donate electrons explains its important role
in oxidation-reduction (redox) reactions
and the scavenging of free radicals.
 Copper is a critical functional component of
a number of essential enzymes, known as
cuproenzymes.
• Energy production:
The copper-dependent enzyme, cytochrome c oxidase,
plays a critical role in cellular energy production. By
catalyzing the reduction of molecular oxygen (O2) to
water (H2O).
• Connective tissue formation:
Another cuproenzyme, lysyl oxidase, is required for the
cross-linking of collagen and elastin, which are essential
for the formation of strong and flexible connective
tissue.
 Iron metabolism:
Two copper-containing enzymes, ceruloplasmin (ferroxidase I)
and ferroxidase II have the capacity to oxidize ferrous iron (Fe2+)
to ferric iron (Fe3+).
 Central nervous system:
A number of reactions essential to normal function of the brain
and nervous system are catalyzed by cuproenzymes
 Neurotransmitter synthesis, metabolism and the
formation and maintenance of myelin:
The myelin sheath is made of phospholipids whose synthesis
depends on cytochrome c oxidase activity.
 Melanin formation:
The cuproenzyme, tyrosinase, is required for the formation of the
pigment melanin.
• Antioxidant Functions:
 Superoxide dismutase:
functions as an antioxidant by catalyzing the conversion of
superoxide radicals to hydrogen peroxide, which can
subsequently be reduced to water by other antioxidant enzymes.
 Ceruloplasmin: Free copper and iron ions are powerful
catalysts of free radical damage.


By binding copper, ceruloplasmin prevents free
copper ions from catalyzing oxidative damage.
The ferroxidase activity of ceruloplasmin (oxidation
of ferrous iron) facilitates iron loading onto its
transport protein, transferrin, and may prevent free
ferrous ions (Fe2+) from participating in harmful free
radical generating reactions.
 Regulation of gene expression:
 Copper-dependent transcription factors
regulate transcription of specific genes.
Deficiency:
 Clinically evident or frank copper deficiency is
relatively uncommon.
 Anemia that is unresponsive to iron therapy but
corrected by copper supplementation.
 Abnormal neutropenia and increased
susceptibility to infection.
 Less common features of copper deficiency may
include loss of pigmentation, neurological
symptoms, and impaired growth
• Disease Prevention
 Cardiovascular diseases:
Increased serum copper levels have been associated with
increased cardiovascular disease risk .
 Immune system function:
Development and maintenance of immune system
function, but the exact mechanism of its action is not yet
known.
 Osteoporosis: lysyl oxidase, is required for crosslinking of collagen, a key element in the organic matrix
of bone.
• The Adequate Intake (AI):
The RDA for copper 900 mcg/day for adults
IODINE
 Iodine, a non-metallic trace element.
 Iodine is an essential component of the thyroid
hormones, T3 and T4 and is therefore, essential
for normal thyroid function
 Deficiency: Thyroid enlargement (goiter)
 Disease Prevention: Radiation-induced thyroid
cancer.
 Disease Treatment: Fibrocystic breast
condition.
 Nutrient Interactions:
 Selenium deficiency can exacerbate the effects
of iodine deficiency.
 Acute Toxicity:
Is rare and usually occurs only with doses of many
grams.
Symptoms of acute iodine poisoning include
burning of the mouth, throat, and stomach,
fever, nausea, vomiting, diarrhea, a weak
pulse, and coma.
 Drug Interactions:
 Amiodarone contains high levels of iodine and may affect
thyroid function.
 Medications used to treat hyperthyroidism, such as
propylthiuracil (PTU) and methimazole may increase the
risk of hypothyroidism.
 Lithium in combination with pharmacologic doses of
potassium iodide may result in hypothyroidism.
 Pharmacologic doses of potassium iodide may
decrease the anticoagulant effect of warfarin .
 The Adequate Intake (AI):
Given the importance of sufficient iodine during prenatal
development and infancy, pregnant and breastfeeding
women should consider taking a supplement providing 150
mcg of iodine/day.
OPTIMIZATION OF INTAKE OF TRACE
ELEMENTS
 Prevention of deficiency states cannot be regarded as the
only end point in terms of provision of micronutrients.
Some measure of functional benefit would appear to be
most valuable, as improved immune function and
improved antioxidant .
 Laboratory tests are of relatively little value with regards
to assigning optimal levels of intake.
 Most of the laboratory tests are affected by illness, either
by the acute-phase reaction with changes in carrier
proteins, or by altering the distribution of the trace
elements themselves.
 SUGGESTED PROVISION OF MICRONUTRIENTS
IN CRITICALLY-ILL PATIENTS
 Ideally, most critically-ill patients will meet their
micronutrient requirements by the enteral route.
 In practice, intake of nutrients by the enteral route will
be limited and hence intravenous supply should be
considered.
 Berger & Shenkin have suggested provision of
approximately 10 mg Zn, 1·3 mg Cu, chromium 20-35
mcg and 100 mg Se in the intensive care patient.
 This level of provision rising to 40 mg Zn, 3·75 mg Cu
and 375 mg Se in burn patients.
 FACTORS AFFECTING THE MICRONUTRIENT
STATUS OF A SEVERLY-INJURED PATIENT
• 1) The status on admission
as those consuming excess alcohol, or the
elderly.
• 2) Increased requirements to meet
metabolic demands
due to hypercatabolism which is associated
with severe illness
 3) Increased losses
Severely-ill patients , blood loss, those who require
haemodialysis or peritoneal dialysis, or who develop
complications of surgery leading to gastric aspirate
or intestinal fistula losses, will all lose trace
elements.
 4) Reduced provision
Due to the delay in the full nutrition regimen whilst
stabilization the patient condition, so that the
prescribed amounts are not provided in each 24 h
period.
 CONSEQUENCES OF IMPAIRED MICRONUTRIENT STATUS
• Subclinical Deficiency
• Initially there is depletion of stores and of tissue content, with
attempts to compensate either by increased absorption from
the gut or by reduced excretion.
 This stage is followed by a period of reduced intracellular
concentration, leading to some impairment of biochemical
functions. This stage in turn may lead on to a period of nonspecific functional defects where there may be identifiable
problems in metabolism, immune function, certain types of
cognitive function, or in fatigue and work capacity.
 Clinical Deficiency States
Severe micronutrient deficiency leads to deficiency states, with
specific structural or functional changes which are reversible on
provision of the individual micronutrient.
The main effects of subclinical deficiency
are:
 (a) an altered balance of reactive oxygen species and
antioxidants
leading to oxidative damage of polyunsaturated fatty
acids and nucleic acids, with increased production of
pro-inflammatory cytokines;
 (b) impaired immune function with increased
likelihood of infectious complications.
CONCLUSION
 It is often very difficult to correlate the
biochemistry of a dietary deficiency with clinical
symptoms because trace elements have multiple
roles in metabolism.
 The development of biomarkers to measure
oxidative stress means that more reliable and
precise estimates of oxidative stress may be made.
Any
Questions ?
Thank you