Exam 3 review clinical chem 1 lecture Nonessential elements

Ultratrace elements are needed in what units?

ug/dl

trace elements are used in what units?

mg/dl

The collection tube that has no EDTA additive is

royal blue top tube with a RED strip

The collection tube that has K2 EDTA for trace metals

royal blue collection tube

definition of atomic emission spectroscopy

• quantification of an element by measuring the intensity of emitted radiation from an aerosolized sample

definition and pathway of atomic absorption spectroscopy

• determination of element quantity through the absorption of optical radiation by free atoms in the gas phase

same principle, difference is that atomic abs measures light absorbed by atoms when in ground state that jump to higher energy level

Aluminum concentrates in 

bone (50%) and lung (25%)

Is aluminum nonessental or essential?

nonessential (toxic)

What is the major protein responsible for transporting aluminum in blood?

Transferrin 

What is the main organ for excreting aluminum?

kidney

Majority of aluminum is excreted in , where else is it excreted?

urine (95%), bile (2%)

Health effects associated with aluminum

encephalopathy, anemia, bone disease, progressive dementia 

Lab evaluations of aluminum status

ICP-MS and GFAAS; urine and serum samples

fatal conditions caused by arsenic

GI, cardiovascular, hepatic, dermatologic, and renal involvement

which is the more toxic form(s) of arsenic?

inorganic and methylated

What is the best specimen for the laboratory evaluation (ICP-MS and GFAAS) for arsenic

urine (hair and nails also suitable, but urine is the best)

Which nonessential element is higher in females and smokers? why?

Cadmium; They have less ions than males and nonsmokers, so they absorb cadmium more

Health effects and toxicity of cadmium?

• it plays no role in human physiology

• affects liver, bone, immune, blood, pulmonary, and nervous systems

Lab evaluation of cadmium status

ICP-MS and GFAAS; found in red blood cells (80%) or urine

Which form of chromium is easier to absorb, and therefore more toxic?

Cr6+ 

Which mutation is associated with hemochromatosis

C282Y in HFE gene

What are the two forms of chromium?

Cr6+ and Cr3+

role of C3+ form of chromium for insulin ?

It is an essential element for insulin action- enhances activity

Cr6+ role and toxicity 

oxidizing agent- which is dangerous as it causes free radicals, which are associated with carcinogens

Chromium causes toxicity in the body, how?

Lung irritation and dermatitis are more common; liver, kidney, and immune system 

How much lead is absorbed by the RBCs when it gets either ingested or inhaled?

99%

Excretion of lead

Urine accounts for 76% of excretion, 16% in feces, and remainder in hair, sweat, and nails

Health effects and toxicity of lead

• no physiological role in body

• interferes with heme synthesis 

• higher absorption in children; leads to neurologic symptoms and low IQ, anemia

Manganese absorption

primarily ingestion; inhalation, and dermal limited

Which of the following nonessential/toxic elements aids in metalloenzyme and element activation

Manganese

Where is manganese found in the body?

fat and bones

What accounts for the majority of excretion of manganese?

bile 

Absorption of mercury, which pathways and what is the most common route?

Inhalation is the most common way to absorb mercury; ingestion, cutaneous, injection, dental

Health effects and toxicity of mercury poisoning

no physiologic role

• CNS and PNS toxicity occurs; it can damage organs/tissues before symptoms occur

CV-AAS is a method that can be used to evaluate which nonessential/toxic element?

Mercury

Which element is an important cofactor for several enzymes?

Molybdenum

Selenium absorption

Ingestion is most common (up to 50%) of diet is absorbed

Selenium excretion

Urine accounts for most excretion ; some in sweat and exhalation

Toxic states of what element cause tachycardia, GI, and CNS symptoms

Selenium

Selenium health effects

important antioxidant and for thyroid hormone synthesis

Deficient states of what element lead to cardiomyopathy (Keshan disease); Kashin-Beck disease (endemic osteoarthritis) 

Selenium

The majority (50%) of copper is absorbed by? and how?

diet, through the binding of an amino acid 

Transported copper is bound to

ceruloplasmin (95%) and albumin

The major copper transporter

Ceruloplasmin

How is copper associated with the enzyme ferroxidase?

Copper is an essential cofactor and structural component in ferroxidase

Majority (98%) of copper is excreted through what?

Bile 

The hallmark symptom of Menke’s Kinky hair syndrome results from

decreased copper, which decreases melanin and collagen production

What gene is affected by Menke’s Kinky hair syndrome?

Atb78

Menke’s kinky hair syndrome disease cause and cure

• X-linked defect in gene Atb78

• severe cerebellar and cerebral degeneration, failure to thrive, osteoporosis, motor delay, and death within the first decade of life (3 years)

• Treated with Cu Histidine if caught early

Disease conditions of copper deficiency 

microcytic-hypochromic anemia, neutropenia, heart disease, bone and joint osetoarthritis, hypothermia, hypercholesterolemia

Excess copper can result from

oral contraceptives, pregnancy, and infections

Excess copper can be treated with? Provide an example

chelating agents; example: Penicillamine

What is Wilson’s disease?

inherited autosomal defect in Cu2+ metabolism

• copper accumulation in liver, brain, kidney, and cornea of the eye (Kayser -Fleisher rings)

• no copper is found in serum due to a decrease in ceruloplasmin, main copper transporter

What are Kayser-Fleisher rings?

A copper ring around the eye due to excess copper accumulation

how can Wilson’s disease be detected?

decreased liver function, increased copper in urine (>500ug/dl)

Which enzyme requires copper as cofactor?

Lysyl oxidase - responsible for collagen formation

Primary source of iron

RBC turnover and diet (10-20mg Fe)

Iron functions in body

• RBC (Heme synthesis)

• Metabolism (glucose metabolism)

• Production of enzymes required for cytogenesis, synthesis of Amino Acid, neurotransmitters, and hormone

• Immune response

• Cognitive function (in kids)

TIBC and iron relationship

Inverse

All irons in blood are protein-bound (transferrin), and Each transferrin molecule can bind

Two Fe3+ (ferric) molecules

When inflammation occurs, what happens to transferrin

It would decrease

Iron-transferrin complexes are endocytosed via cells expressing transferrin receptors, these cells include? And where are they in?

Reticulocytes (bone marrow); they are in endothelial cells in liver and spleen

Iron turnover rate (half life time)

½ life - about 1-2 hours (very fast)

Most of the body’s iron for heme is

recycled from aged RBCs destroyed by tissue macrophages in the spleen

What cells maintain a storage pool of iron

macrophages

If RBC destruction is greater than RBC production, what happens to macrophages

Iron builds up within the macrophage

A contributing factor to anemia if chronic disease affecting iron storage and release is 

That macrophages are too busy fighting the source of inflammation to have time to release iron to the red blood cells, dropping red blood cell production even with adequate iron storage. 

Total iron binding capacity equation

(TIBC)=[Fe] Serum + UIBC

How to calculate % transferrin saturation

([Fe] / TIBC ) x 100

What is total iron binding capacity (TIBC)?

how much iron can maximally bind to all transferrin,

serum iron decreased in

Iron deficiency anemia, anemia of chronic disease, liver infection, inflammation, decreased or defective p450

What is cytochrome p450?

an enzyme that relies on iron to perform its functions, which include oxidizing and metabolizing various compounds (ie. drugs)

serum iron is increased in 

megaloblastic anemia, hemolytic anemia, sideroblastic anemia, thalassemia, hepatic necrosis, bone marrow hypoplasia, and iron overload

transferrin saturation and iron levels have what type of relationship?

directly proportional

Hepcidin function

iron regulatory hormone

to assess iron availability in hemoglobin production,

can check Zn-protoporphyrin or free erythrocyte protoporphyrin (FEP) ; when iron decreases, FEP is increased

late symptom of iron overload

diabetes mellitus due to iron precipitation in pancreas

early symptom of hemochromatosis

liver cirrhosis, cardiomyopathy

What is the second most abundant trace element in the body? source of zinc

Zinc; Source of zinc is dietary (red meat and fish).

zinc is excrete =d the most through

fecal matter

Deficiency in zinc causes

growth inhibition, testicular atrophy