Clinical Chemistry 2-Lec Trace Elements & Acid-Base Balance Mechanisms PDF

# CLINICAL CHEMISTRY 2 - Lec ## MIDTERMS | LECTURE ## 1ST SEM | 3RD YEAR ### **TRACE ELEMENTS & ACID-BASE BALANCE MECHANISMS** #### SERAPIO, EsterrRrrrrrRRrr #### Instructor: Dephanie Destor **• Metallothionein** - sequesters & stored copper ## Proven Essential | Probably Essential | Nonessent...

# CLINICAL CHEMISTRY 2 - Lec ## MIDTERMS | LECTURE ## 1ST SEM | 3RD YEAR ### **TRACE ELEMENTS & ACID-BASE BALANCE MECHANISMS** #### SERAPIO, EsterrRrrrrrRRrr #### Instructor: Dephanie Destor **• Metallothionein** - sequesters & stored copper ## Proven Essential | Probably Essential | Nonessential to date ### Trace - Iron - Copper - Zinc - Manganese - Cobalt - Selenium - Molybdenum - Chromium - Iodine ### Ultratrace - Nickel - **Vanadium** - **Tin** - Aluminum - Arsenic - Cadmium - Fluoride - **Gold** - **Lead** - **Mercury** - **Silicon** ## TRACE ELEMENTS **What:** Minerals present in very small amounts but are very essential for physiologic processes **• Roles**: - Required only in minute quantities - Enzyme Function - Hormone production - Overall Cellular Health **• Associated with:** Enzymes and Proteins **NOTES:** - Deficiency impairs a biochemical or functional process. - Replacement corrects the impairment ## Laboratory Determination 1. Anti-coagulated Blood 2. Low concentration and ubiquitous in nature - Ubiquitous: found everywhere 3. Atomic Absorption Spectrophotometry - Prevent contamination ## COPPER - THIRD most abundant trace element - Where in Diet: shellfish, legumes, nuts, liver - Dietary requirement: 1.5-3.0 mg/day - Participates in: 1. Cellular Respiration 2. DNA and RNA reproduction 3. Maintains Cell Membrane Integrity 4. Sequestration of free radicals ## Distribution & Copper-containing proteins - Liver: highest copper concentration - Copper-containing proteins: - Ceruloplasmin: a-2 globulin - Functions as: ferroxidase enzyme - Catalyzes the oxidation of ferrous ion to ferric ion - NOTE: Ceruloplasmin is NOT a transporter protein since the copper is NOT exchangeable (Eastwood, 2003) - Albumin-bound - Transcuperin - transports copper ## Clinical Correlation ### A. Copper Deficiency - Premature infants and undernourished children - Contributing factor in adults w/ osteoporosis & CVD (cardiovascular diseases) - Menke's Disease or kinky hair syndrome - Decreased ceruloplasmin level= diminished copper concentration in the hair ### B. Copper Toxicity: Increased copper in tissue and serum - Hypotonia: decreased muscle tone - Acute Copper poisoning - Fungicides containing copper sulfate - Wilson's Disease: genetically determined copper accumulation disease - Inability of the body to metabolize copper - Leads to accumulation of copper in the: - (a) liver, (b) brain, and (c) cornea of eyes - Lab Diagnosis: Increased Serum copper - Manifestations: - Neurologic Disorder/Mental retardation - Liver Dysfunction:Hepatitis, cirrhosis, renal failure - Kayser-Fleischer rings in cornea: green-brown discoloration ## Analytical Methods ### A. For Copper - Can use: Serum or Urine - Measured by: - Atomic Absorption Spectroscopy (method of choice) - Colorimetric Method ### B. For ceruloplasmin - Photometric Method - Immunochemical Methods: nephelometry ## Reference Interval - Serum Copper: - Male: 70-140 ug/dL (11-22 umol/L) - Female: 80-155 ug/dL (13-14 umol/L) - Ceruloplasmin: 23-50 mg/dL # CLINICAL CHEMISTRY 2 - Lec ## MIDTERMS | LECTURE ## 1ST SEM | 3RD YEAR ### **TRACE ELEMENTS & ACID-BASE BALANCE MECHANISMS** #### SERAPIO, EsterrRrrrrrRRrr #### Instructor: Dephanie Destor ## ZINC - SECOND most abundant trace element - Roles/Functions: - Cofactor for almost 300 enzymes - Important in protein and nucleic acid synthesis - Essential for the synthesis and action of insulin ## Zinc-Containing Proteins - Carbonic anhydrase - Alkaline phosphatase (ALP) - DNA & RNA polymerase - Carboxypeptidase - Alcohol dehydrogenase - Superoxide dismutase ## Metabolism and Distribution - Zinc is distributed/ absorbed in the: 1. Duodenum: absorbs zinc 2. Metallothionein: transfers zinc to portal blood - In blood: bound to albumin and a-2 macroglobulin 3. Muscle & Bones: Contain most of the body's zinc stores; slow turnover - Half life: 300 days 4. Liver: metallothionein-bound zinc; can be readily mobilized - Half life: approximately 2 weeks ## Clinical Significance ### A. Zinc Deficiency: - Common in patients with the following disorders: - Diabetes Mellitus - Alcohol Abuse - Malabsorption Syndromes - Liver and Kidney Disease - Acrodermatitis enteropathica: rare autosomal recessive disorder with impaired intestinal absorption & transport of zinc ## Laboratory Determination - Factors to consider: 1. Diurnal Variation: Zinc is higher in the morning (am) 2. Postprandial variations: Zinc is higher when fasting 3. Serum values: 10% higher than plasma values 4. RBC zinc 10 higher than plasma zinc ## Methods: - Method of choice: Atomic Absorption Spectroscopy 1. Flame Atomic Absorption Spectrophotometry (FAAS): method of choice for Zinc in body fluids 2. Inductive Coupled Plasma -Mass Spectrometry (ICP-MS): reference testing in serum or plasma ## Plasma Reference Value - 70-120 ug/dL (10.7-18.4 umol/L) # IRON - MOST abundant trace element: 40-50 mg iron/kg body weight - Roles/ Functions: - Iron-containing proteins: - Hemoglobin: needs iron to function right - Collagen - Tyrosinase - Catecholamines - Cell-mediated immunity - Modulate proliferation & differentiation of lymphocytes - Affects immune potential of macrophages ## Distribution - Iron is distributed in: 1. Hemoglobin in RBCs 2. Ferritin & Hemosiderin: iron stores 3. Body tissued: myoglobin & non-heme enzymes 4. Iron bound to transferrin ## Metabolism and Regulation - Dietary iron: Ferrous form for reabsorption - Iron absorption (in ferrous form) is facilitated by: - Ascorbic acid & other reducing agents - Acid pH in the stomach - Only 5-10% of dietary iron is absorbed - Transferrin: glycoprotein that transports iron - Synthesized in the liver - High affinity with ferric ion (not in ferrous form) - Ferritin: found in virtually all cells - Stored form of iron - Measured for IDA diagnosis - IDA= iron deficiency anemia - Increased serum ferritin is due to: - Fever - Acute infections - Rheumatoid arthritis - Viral hepatitis ## Analytical Methods ### A. Direct Measurements: - Quantitative, specific, & sensitive - Involve invasive procedures such as: - Quantitative phlebotomy - Bone marrow biopsy - Liver biopsy ### B. Indirect Measurements - Serum iron is measured by: 1. Colorimetric method 2. Atomic Absorption Spectroscopy (AAS) - Serum transferrin is measured by: 1. Direct Immunoassay 2. TIBC (total iron binding capacity): maximum amount of iron that can bind to serum transferrin ## Transferrin Ration: - ratio of the plasma to TIBC - Serum ferritin is measured by: 1. Immunoradiometric assay (IRMA) 2. Enzyme Linked Immunosorbent Assay (ELISA) 3. Immunofluorometric Assay 4. Chemiluminescence Assay - Serum Transferrin receptor (TfR) - Useful marker of body iron stores (pregnancy & neonates) - Sensitive measurement of tissue iron deficiency - Zinc Protoporphyrin (ZnPP) - Zinc-for-iron substitution in IDA: increased ZnPP - Substitution in bone marrow - Extraction with ethyl acetate - HPLC/ High performance liquid chromatography: method of choice ## Clinical Significance ### A. Iron Deficiency - Iron Depletion - Iron storage: decreased/ absent - Serum iron & hemoglobin: preserved - Iron Deficiency Anemia (IDA): most advanced stage of iron deficiency ### Causes: 1. Blood loss due to GI Bleeding 2. Chronic drug ingestion 3. Parasitic 4. Impaired absorption of iron 5. Renal failure ### B. Iron Overload - Hereditary hemochromatosis: most common - Sideroblastic anemia - Chronic ingestion of medicinal iron - Chronic hepatitis ## Reference Interval - Total Iron: 60-150 ug/dL - TIBC: 250-400 ug/dL - Iron Sat'n: 20-55% - Ferritin: - Male: 15-200 ug/L - Female: 12-200 ug/L