Trace Elements

Definition

Trace elements (also called trace minerals Minerals Electrolytes) are minerals Minerals Electrolytes required in small amounts (1–100 mg/day for adults):

• Have several functions, including in enzyme systems, energy metabolism, and oxygen transport
• Intake of large amounts over a long period can produce toxic effects.
• Required intake is expressed as Recommended Dietary Allowance (RDA): dietary intake sufficient to meet the daily nutrient requirements of 97% of the individuals in a specific life stage group
• If data regarding RDA are limited, Adequate Intake ( AI AI Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease) is used to indicate the amount estimated to be sufficient to maintain a healthy state.

Chromium

General description

• Symbol: Cr
• Multiple ionic states:
  • Dietary chromium: trivalent state
  • Cr⁴⁺: toxic form

Functions

• Potentiates insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
• Influences carbohydrate and lipid metabolism Lipid Metabolism Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Lipid Metabolism

Intake and metabolism

• RDA: 20–35 μg/day for adults
• Source: processed meats, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, brewer’s yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology, whole grains, cereals, fruits, vegetables
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
• Transport ( circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment): bound to albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests and transferrin Transferrin An iron-binding beta1-globulin that is synthesized in the liver and secreted into the blood. It plays a central role in the transport of iron throughout the circulation. Heme Metabolism
• Regulation:
  • ↑ Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption with vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies as well as in zinc and iron deficiency
  • ↓ Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption with antacids and NSAIDs NSAIDS Primary vs Secondary Headaches
  • Excretion: in feces

Deficiency and toxicity Toxicity Dosage Calculation

• Chromium deficiency is generally seen in:
  • Conditions characterized by increased catabolism and metabolic demands (critical illness)
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries 
  • Short bowel syndrome Short bowel syndrome Short bowel syndrome is a malabsorptive condition most commonly associated with extensive intestinal resection for etiologies such as Crohn’s disease, bowel obstruction, trauma, radiation therapy, and vascular insufficiency. The short length of bowel results in insufficient surface area for fluid and electrolyte absorption. Short Bowel Syndrome 
  • Chronic total parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter (especially in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus and increased insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin requirements)
• Excess:
  • Dietary chromium has poor oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics (so generally nontoxic). 
  • Hexavalent chromium (Cr (VI)) toxicity Toxicity Dosage Calculation (airborne): ↑ risk of lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer in stainless steel workers
  • Pentavalent, or Cr (V), and Cr (VI) (by inhalation): bronchogenic cancer, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions ulcers, dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema)

Copper

General description

• Symbol: Cu
• High concentrations in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types 
• In acute-phase response Acute-phase response An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma. Tumor Necrosis Factor (TNF), plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products levels are increased.
• Heritable diseases associated with inborn errors of copper metabolism:
  • Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder characterized by features of copper toxicity Toxicity Dosage Calculation
  • Menkes disease Menkes Disease An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of hypothermia, feeding difficulties, hypotonia, seizures, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including protein-lysine 6-oxidase; ceruloplasmin; and superoxide dismutase. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. Alopecia: X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) genetic disorder characterized by defective transport protein mediating copper uptake from the intestine, leading to copper deficiency

Functions

• Involved in oxidation–reduction reactions
• Integral component of important enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
  • Ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease (copper transporter and ferroxidase) 
  • Cytochrome c oxidase Oxidase Neisseria (electron transport) 
  • Zinc–copper superoxide dismutase Superoxide dismutase An oxidoreductase that catalyzes the reaction between superoxides and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Myeloperoxidase Deficiency (antioxidant defense)
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS monooxygenase (neurotransmitter synthesis Synthesis Polymerase Chain Reaction (PCR)) 
  • Lysyl oxidase Oxidase Neisseria ( collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology cross-linking, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation) 
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS β-hydrolase ( skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pigmentation) 
  • Tyrosinase ( melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis production)

Intake and metabolism

• RDA:
  • Children: 340 µg daily
  • Adults: 900 µg daily
• Source:
  • Highest content in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Vegetable products: vegetables, grains, and pulses (leguminous seeds such as beans, peas, and lentils) 
  • Meat, fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing, and poultry
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
• Copper is taken up by the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and is incorporated into ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease.
• Ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease transports copper from the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy to peripheral tissues.
• Regulation:
  • Excretion via GI secretions and bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy (50% each)
  • Copper homeostasis Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Cell Injury and Death is maintained through the excretion process, especially through the GI tract (preventing deficiency and toxicity Toxicity Dosage Calculation).

Deficiency and toxicity Toxicity Dosage Calculation

• Acquired deficiency:
  • Seen in:
    • Malabsorptive GI surgery (e.g., gastric bypass Gastric bypass Surgical procedure in which the stomach is transected high on the body. The resulting small proximal gastric pouch is joined to any parts of the small intestine by an end-to-side surgical anastomosis, depending on the amounts of intestinal surface being bypasses. This procedure is used frequently in the treatment of morbid obesity by limiting the size of functional stomach, food intake, and food absorption. Gastroesophageal Reflux Disease (GERD)), manifesting with myelopathy or neurologic symptoms similar to those of vitamin B₁₂ deficiency
    • Prolonged parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter (especially in preterm infants)
    • Chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (such as in celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease)
    • Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis
    • Excessive zinc intake
    • Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome (treatment of Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease with chelation and zinc → ↓ copper level)
    • Menkes disease Menkes Disease An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of hypothermia, feeding difficulties, hypotonia, seizures, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including protein-lysine 6-oxidase; ceruloplasmin; and superoxide dismutase. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. Alopecia
  • Manifestations:
    • Depigmentation Depigmentation Vitiligo
    • Muscle weakness
    • Neurologic abnormalities
    • Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
• Excess:
  • Seen in:
    • Accidental ingestion
    • Suicide attempt Suicide attempt The unsuccessful attempt to kill oneself. Suicide
    • Water source contamination
    • Topical creams with copper salts
    • Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease
  • Manifestations:
  • GI symptoms
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Renal and cardiac failure Cardiac failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Heart Failure

Fluoride

General description

• Fluoride (F–): monovalent anion derived from fluorine
• Common in the earth’s crust Crust Dried exudate of body fluids (blood, pus, or sebum) on an area of damaged skin Secondary Skin Lesions as calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes fluoride

Functions

Provides benefits (but not necessary):

• Together with calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, stimulates osteoblastic activity (although reduction in fractures are not seen)
• Used in preventing dental caries

Intake and metabolism

• No RDA due to limited data, but AI AI Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease is defined as:
  • Adult females: 3 mg daily
  • Adult males: 4 mg daily
• Source: found in tea, seafood that contains edible bones or shells (e.g., canned sardines), and fluoridated toothpaste
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
  • About 30% taken up in calcified tissues
  • Most fluoride is in the bones and teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy.
• Excretion: in urine

Deficiency and toxicity Toxicity Dosage Calculation

• Low levels of fluorine in drinking water lead to dental decay. 
• Excess:
  • High levels cause dental fluorosis and mottling of tooth enamel Enamel A hard thin translucent layer of calcified substance which envelops and protects the dentin of the crown of the tooth. It is the hardest substance in the body and is almost entirely composed of calcium salts. Under the microscope, it is composed of thin rods (enamel prisms) held together by cementing substance, and surrounded by an enamel sheath. Teeth: Anatomy.
  • In settings of exposure to Freon vapor or hydrofluoric acid spills, toxicity Toxicity Dosage Calculation can follow inhalation or skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.
  • GI symptoms ( nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea) are noted, but renal and cardiac failure Cardiac failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Heart Failure occurs in severe cases.

Iodine

General description

• Symbol: I
• Essential component of the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types triiodothyronine Triiodothyronine A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones (T₃) and thyroxine Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroid Hormones (T₄)
• Deficiency remains a public health issue in resource-limited countries.

Functions

Physiologic actions of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types involve: 

• Growth and development  
• Control of metabolic processes in the body 
• Energy production
• Lipolysis Lipolysis The metabolic process of breaking down lipids to release free fatty acids, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the digestive tract, circulating lipids in the blood, and stored lipids in the adipose tissue or the liver. A number of enzymes are involved in such lipid hydrolysis, such as lipase and lipoprotein lipase from various tissues. Nonalcoholic Fatty Liver Disease 
• Regulation of gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis and glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis

Intake and metabolism

• RDA:
  • Children 1–8 years of age:  90 µg daily
  • Children 9–13 years of age: 120 µg daily
  • Adolescents and adults: 150 µg daily
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care: 220 µg daily
  • Lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding: 290 µg daily
• Source:
  • Seafood
  • Foods grown in iodine-rich soil
  • Iodized salt
  • Bread and dairy products
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: proximal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
  • Goes into circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and stored in the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy
  • T₃ and T₄ are secreted by the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy.
• Excretion:
  • In urine
  • GI losses are reabsorbed.

Deficiency and toxicity Toxicity Dosage Calculation

• Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones deficiency:
  • From inadequate intake
  • Effects:
    • Goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter 
    • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism 
    • Increased risk of miscarriage Miscarriage Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks’ gestation. However, the layperson use of the term “abortion” is often intended to refer to induced termination of a pregnancy, whereas “miscarriage” is preferred for spontaneous loss. Spontaneous Abortion, preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth, congenital Congenital Chorioretinitis fetal abnormalities 
    • High incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of neonatal death
• Excess:
  • From dietary supplements, prescription medications, radiographic contrast agents Contrast agents Substances used to allow enhanced visualization of tissues. Computed Tomography (CT)
  • Effects:
    • Abrupt increase in iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones in endemic goiter Endemic goiter A form of iodine deficiency disorders characterized by an enlargement of the thyroid gland in a significantly large fraction of a population group. Endemic goiter is common in mountainous and iodine-deficient areas of the world where the diet contains insufficient amount of iodine. Goiter or iodide Iodide Inorganic binary compounds of iodine or the i- ion. Thyroid Hormones deficiency → hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism
    • Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones administration in Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis → may induce hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism

Iron

General description

• Symbol: Fe
• Most abundant essential trace element in the human body
• Forms of iron (total content of iron in the body of 3–4 g in males):
  • 75% in heme proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
    • In the form of hemoglobin (for oxygen transport)
    • Myoglobin Myoglobin A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. Rhabdomyolysis (for oxygen storage in tissues)
    • Cytochrome c (electron transport)
    • Cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury
    • Peroxidases
  • 20%–30% in storage form:
    • Ferritin Ferritin Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store iron in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (apoferritins) made of 24 subunits of various sequences depending on the species and tissue types. Hereditary Hemochromatosis (major intracellular iron-storage protein)
    • Hemosiderin Hemosiderin Heme Metabolism ( ferritin Ferritin Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store iron in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (apoferritins) made of 24 subunits of various sequences depending on the species and tissue types. Hereditary Hemochromatosis breakdown product)

Functions

• Oxygen transport
• Essential component of a number of enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes necessary in:
  • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure and RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Antibody synthesis Synthesis Polymerase Chain Reaction (PCR)
• Metalloenzymes (needed in tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids, dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, and noradrenaline synthesis Synthesis Polymerase Chain Reaction (PCR)) 
• Other biologic effect(s): able to cycle between ferrous (Fe²⁺) and ferric (Fe³⁺) forms, catalyzing reactions that produce reactive oxygen species Reactive oxygen species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include singlet oxygen; superoxides; peroxides; hydroxyl radical; and hypochlorous acid. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids. Nonalcoholic Fatty Liver Disease, causing oxidative damage

Intake and metabolism

• RDA:
  • Women of childbearing age: 18 mg/day (due to losses in menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle)
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care: 27 mg/day
  • Adult males: 8 mg/day 
• Sources:
  • Heme iron: meat, poultry, fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing
  • Nonheme iron: vegetables, fruits, fortified food products
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
  • In the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
  • ↑ By vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies 
  • ↓ By calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, phytic acid, tannates
• Transported in the blood bound to transferrin Transferrin An iron-binding beta1-globulin that is synthesized in the liver and secreted into the blood. It plays a central role in the transport of iron throughout the circulation. Heme Metabolism, then taken up in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis
• Losses: through desquamated skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, bleeding
• Regulation:
  • Certain conditions require a decrease or increase in iron absorption Iron absorption Digestion and Absorption.
  • Hepcidin Hepcidin Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity. Hereditary Hemochromatosis: liver-derived peptide regulating the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products iron concentration
    • ↑ Iron: ↑ hepcidin Hepcidin Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity. Hereditary Hemochromatosis to reduce iron absorption Iron absorption Digestion and Absorption
    • ↑ Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation: ↑ hepcidin Hepcidin Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity. Hereditary Hemochromatosis to limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation iron availability to microorganisms
    • ↑ Erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology: ↓ hepcidin Hepcidin Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity. Hereditary Hemochromatosis to increase iron for hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis

Deficiency and toxicity Toxicity Dosage Calculation

• Deficiency:
  • Seen as microcytic hypochromic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types:
    • Blood loss
    •  ↓ Intake or inability to keep up with demand (such as in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding)
  • Manifestations include pallor, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, and shortness of breath Shortness of breath Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea.
• Excess: seen in hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis, iron poisoning Iron Poisoning Metal Poisoning (Lead, Arsenic, Iron)

Selenium

General description

• Symbol: Se
• Discovered during experiments in rats: Selenium was shown to protect rats against dietary liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage.

Functions

• Part of active site Active site Area of an enzyme that binds to specific substrate molecules in order to facilitate a reaction. Basics of Enzymes of glutathione peroxidase Glutathione peroxidase An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. Cell Injury and Death, an antioxidant enzyme
• Regulates immune, thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy, and reproductive function

Intake and metabolism

• RDA:
  • Children: 20 μg/day
  • Adults: 55 μg/day
• Source: seafood, kidney and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, and grains
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy (methionine absorptive pathway)
• Exerts effects through 2 forms:
  • Selenomethionine: storage pool
  • Selenocysteine: active form of selenium found in proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
• Excretion: in urine

Deficiency and toxicity Toxicity Dosage Calculation

• Deficiency:
  • Seen in:
    • Aging
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Reduced intake (seen in endemic areas)
    • Total parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter (TPN; not supplemented with selenium)
  • Effects:
    • Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types (Keshan disease in China, from low-Se diets)
    • Skeletal muscle dysfunction
    • Thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis can increase with selenium deficiency
    • Impairment of both innate and adaptive immunity
• Excess:
  • Seen in increased supplementation
  • Effects:
    • GI: nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Neurologic: altered mental status Altered Mental Status Sepsis in Children, visual loss, peripheral neuropathy Neuropathy Leprosy
    • Dermatologic: hair loss, nail changes

Zinc

General description

• Symbol: Zn
• Essential element related to a common deficiency worldwide
• In resource-limited countries, supplementation helps reduce serious infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and improve immunity.

Functions

• Important in immune response
• Deficiency leads to phagocytic impairment and decreased IL-2 and immunoglobulin production.
• Stabilizer of the molecular structure of cellular constituents and membranes 
• Participates in the metabolic activity of carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates, proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, and lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids
• Plays an important role in growth (cell proliferation, differentiation, and metabolic activity)
• Involved in wound repair and healing

Intake and metabolism

• RDA varies by age and sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria:
  • Children: 3 mg daily
  • Adult females: 8 mg daily (higher in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and lactation Lactation The processes of milk secretion by the maternal mammary glands after parturition. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including estradiol; progesterone; prolactin; and oxytocin. Breastfeeding)
  • Adult males: 11 mg daily
• Source:
  • Shellfish (especially oysters), beef, and other red meats
  • Nuts, whole grains, legumes
• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: mainly jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy and duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
  • Zinc is released and forms complexes with amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids, phosphates, and histidines.
  • These complexes are absorbed through the intestines → portal circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment → liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
• Regulation:
  • Metallothionein (in the enterocyte) regulates absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption by binding heavy metals (has more affinity for copper) to reduce oxidative damage.
  • Excretion: mainly via GI tract (10% in urine)

Deficiency and toxicity Toxicity Dosage Calculation

• Deficiency
  • Seen in:
    • Exocrine pancreatic insufficiency Exocrine pancreatic insufficiency A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes (lipase; proteases; and amylase) by the exocrine pancreas into the duodenum. This condition is often associated with cystic fibrosis and with chronic pancreatitis. Malabsorption and Maldigestion
    • Reduced intake
    • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion syndromes
    • Gastric bypass Gastric bypass Surgical procedure in which the stomach is transected high on the body. The resulting small proximal gastric pouch is joined to any parts of the small intestine by an end-to-side surgical anastomosis, depending on the amounts of intestinal surface being bypasses. This procedure is used frequently in the treatment of morbid obesity by limiting the size of functional stomach, food intake, and food absorption. Gastroesophageal Reflux Disease (GERD) surgeries
    • Alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis  
    • TPN
    • Acrodermatitis enteropathica: autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease with impaired zinc absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
  • Manifestations:
    • Growth retardation Growth Retardation Failure of a fetus to attain expected growth. Fetal Alcohol Spectrum Disorder
    • Sexual impairment (delayed maturation, impotence, hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism, oligospermia)
    • Immune dysfunction
    • Impaired wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions (e.g., decubitus ulcers, vesiculobullous, and pustular lesions) 
    • Hair changes (e.g., hair loss)
• Excess:
  • Can occur with contaminated food or beverages
  • Manifests with abdominal pain Abdominal Pain Acute Abdomen, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia

Other Trace Elements

• Molybdenum:
  • Deficiency: neurologic abnormalities
  • Toxicity Toxicity Dosage Calculation: fetal and reproductive abnormalities
• Manganese:
  • Deficiency:
    • Impaired growth and skeletal development 
    • Reproductive abnormalities
    • Dysfunction in lipid and carbohydrate metabolism
    • Upper body rash Rash Rocky Mountain Spotted Fever
  • Toxicity Toxicity Dosage Calculation:
    • Neurotoxicity
    • Parkinson-like symptoms
    • Psychosis
    • Pneumoconiosis Pneumoconiosis Pneumoconiosis is an occupational disease that results from the inhalation and deposition of mineral dusts and other inorganic particles in the lung. It can be categorized according to the type of causative particle involved or by the type of response provoked. Pneumoconiosis
• Boron:
  • Deficiency: unclear, as biologic function is undetermined 
  • Toxicity Toxicity Dosage Calculation: GI symptoms, developmental defects, male sterility, testicular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation

Clinical Relevance

• Iron deficiency anemia Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Iron Deficiency Anemia: most common type of anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types worldwide. Iron deficiency anemia Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Iron Deficiency Anemia is due to a decreased supply, an increased loss, or an increased demand for iron. The RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology are microcytic and hypochromic. Iron studies Iron Studies Iron Deficiency Anemia are pivotal to diagnosis. The key to treatment is correction of the cause of the iron deficiency and iron supplementation Iron Supplementation Iron Deficiency Anemia.
• Wilson disease Wilson disease Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7B gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease ( hepatolenticular degeneration Hepatolenticular degeneration Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder caused by various mutations in the ATP7b gene, which regulates copper transport within hepatocytes. Dysfunction of this transport mechanism leads to abnormal copper accumulations in the liver, brain, eyes, and other organs, with consequent major and variably expressed hepatic, neurologic, and psychiatric disturbances. Wilson Disease): autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder associated with mutations in the ATP7B gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, which regulates copper transport. This mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations causes copper to accumulate in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy, and other organs. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often present  with hepatic, neurologic (often resembling Parkinsonism Parkinsonism West Nile Virus), and psychiatric symptoms. Diagnosis is established by detection of corneal deposits of copper ( Kayser-Fleischer rings Kayser-Fleischer rings Copper deposits in Descemet’s membrane of the cornea, manifested as green-brown rings that encircle the iris. Wilson Disease), low plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products ceruloplasmin Ceruloplasmin A multi-copper blood ferroxidase involved in iron and copper homeostasis and inflammation. Wilson Disease, and/or elevated levels of copper in the urine.
• Menkes disease Menkes Disease An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of hypothermia, feeding difficulties, hypotonia, seizures, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including protein-lysine 6-oxidase; ceruloplasmin; and superoxide dismutase. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. Alopecia: inherited X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) copper deficiency. Menkes disease Menkes Disease An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of hypothermia, feeding difficulties, hypotonia, seizures, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including protein-lysine 6-oxidase; ceruloplasmin; and superoxide dismutase. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. Alopecia is caused by a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of the transport protein mediating copper uptake from the intestine, encoded by the ATP7A gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. Inactivating mutations in this gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics result in severe copper deficiency with progressive neurologic deterioration and death during early childhood. The ATP7A gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics is closely related to the gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics responsible for copper overload in Wilson’s disease. 
• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism: condition characterized by the deficiency of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types. Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones deficiency and Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis are the 2 leading etiologies. Clinical features reflect the effects of slowed organ function/decreased metabolic rate. Lab tests show elevated thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH) and a low free T₄. Treatment is with levothyroxine Levothyroxine Thyroid Replacement Therapy.
• Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism: condition caused by sustained overproduction and release of the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types T₃ and T₄. Graves’ disease is the most common cause of hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism. Manifestations are mostly due to the increased metabolic rate and overactivity of the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Lab tests show low TSH and elevated free T₄. Treatment depends on the underlying condition.