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Chem PPT Flashcards, Unit 4 Diabetes Mellitus is a group of metabolic disorders of ___ metabolism Diabetes Mellitus can cause the following lifethreatening episodes: Complications of DM includes: Diabetes was first classified as Juvenile vs. adult onset, then insulin dependent vs. noninsulin dependent and finally: Two other types of DM include: Type 1 DM accounts for __% - __% Type 1 DM presents with: In type 2 DM, insulin deficiency is caused by: loss of pancreatic islet β-cells Type 2 DM accounts for __%: Are patients with type 2 DM dependent on insulin? What is the mechanism for type 2 DM? How is type 2 DM usually treated? Usually occurs in people over: Other causes of DM can include: Gestational DM is defined as: Incidence is between __% and __% Impaired glucose tolerance is defined as: Rare complications of IGT are: There is an increased prevalence of : Hormone that decreases blood glucose Counter-regulatory hormones that increase blood glucose concentrations Insulin is produced by the _______ of the islets of Langerhans of the _____. Carbohydrate Ketoacidosis and hyperosmolar coma Retinopathy, nephropathy, neuropathy and atherosclerosis Type 1 and type 2 Gestational and other types 5 - 10 polyuria, polydipsia, and rapid weight loss loss of pancreatic islet β-cells 90% No. Insulin resistance dietary manipulation, oral hypoglycemic agents, or insulin to control hyperglycemia 40 Genetic defects of β-cell function, Genetic defects in insulin action Exocrine pancreas disease, Endocrinopathies (Cushing syndrome, acromegaly, glucagonoma)Hormones or drugs that induce β-cell dysfunction (dilantin, pentamidine) or impair insulin action (glucocorticoids, thiazides, β-adrenergics), Infection, Uncommon forms of immune-mediated diabetes, Other genetic conditions (Down syndrome, Klinefelter syndrome, porphyria) carbohydrate intolerance of variable severity with onset or first recognition during pregnancy 6-8 people with intermediate glucose levels (140 to 199 mg/dL or 7.8 to 11.1 mmol/L Microvascular disease and renal and retinal CVD Insulin Glucagon, epinephrine, cortisol, growth hormone B-cells, pancreas 1 Chem PPT Flashcards, Unit 4 Insulin is an _______ hormone that stimulates uptake of glucose into fat and muscle. Insulin promotes the conversion of glucose to glycogen or fat for storage. Insulin inhibits glucose production by the liver. Insulin stimulates protein synthesis and inhibits protein breakdown. ______ is the major storage form of insulin and has approximately 10% of insulin potency. Glucose transport is modulated by what two families of proteins? _____ promotes the uptake of glucose and galactose from the lumen of the small bowel and their reabsorption from urine in the kidney. _____ is located on the surface of all cells, and are designated GLUT1 to GLUT14. What does IGF stand for? _____ were previously referred to as nonsuppressible insulin-like activity or somatomedin. IGF exhibit metabolic and growth-promoting effects similar to those of insulin. _____ was previously known as somatomedin C, mediates growth hormone action, and regulates cell growth and differentiation. Synthesis of IGF-1 occurs primarily in the ______. Exogenous administration of IGF-1 produces _______. Deficiency of IGF-1 causes ________. The physiological role of IGF-2 is unknown. Glucagon, epinephrine, and growth hormone have actions ______ to those of insulin. Where is glucagon secreted? What is the major target organ for glucagon? Glucagon stimulates the production of glucose in the liver by _______ and ________ and enhances ketogenesis in the liver. The minor target organ for glucagon is ___________, where the hormone increases lipolysis. Increased secretion of glucagon is primarily regulated by low concentrations of _____ ______. High concentration is regulated by decreased secretion. ______, ______, and ______induce glucagon Anabolic True True True Proinsulin Sodium dependent glucose transporter, and facilitative glucose transporters Sodium dependent glucose transport Facilitative glucose transporters Insulin-like growth factors IGF True IGF-1 Liver Hypoglycemia Dwarfism True Opposite Alpha cells of the pancreas Liver Glyconeogenesis and gluconeogenesis Adipose tissue Plasma glucose Stress, exercise, and amino acids 2 Chem PPT Flashcards, Unit 4 release. Insulin inhibits glucagon release from the pancreas and decreases glucagon gene expression, thereby attenuating its biosynthesis. Increased glucagon concentrations are believed to contribute to the hyperglycemia and ketosis of diabetes. Epinephrine is a ______ secreted by the adrenal medulla. Epinephrine stimulates glucose production via gluconeogenesis and glycogenolysis, and _______ glucose use, thereby _______ blood glucose concentrations. Epinephrine also ______ glucagon secretion and ______insulin secretion by the pancreas. _________ has a key role in glucose counterregulation when glucagon secretion is impaired Phyisical or emotion stress _______ epinephrine production, releasing glucose for energy. What are tumors of the adrenal medulla also known as? What is a polypeptide hormone secreted by the anterior pitutiary gland? What is the anterior pituitary also known as? What is the most abundant hormone produced by the adenohypophysis? During daytime hours, plasma concentrations are ____. In the evening hours, adults and children show a marked _____ 90 minutes after the onset of sleep. Growth hormone stimulate _______, enhances _____, and antagonizes insulin-stimulated glucose uptake. What is the major glucocorticoid synthesized from cholesterol in the zona fasciculata and reticularis of the adrenal cortex? Cortisol is secreted in response to _____. Cortisol stimulates _______and ________ the breakdown of protein and fat. Patients with Cushing Syndrome have _______ level or cortisol due to tumor or hyperplasia of the adrenal cortex and may become _____glycemic. What hormone is secreted by the thyroid gland True True Catecholamine Decreases, increasing Stimulates, inhibits epinephrine increases pheochromocytomas Growth hormone Adenohypophysis Growth hormone Low Rise Gluconeogenesis, lipolysis Cortisol ACTH Gluconeogenesis, increases Increases, hyper Thyroxine 3 Chem PPT Flashcards, Unit 4 and is not directly involved in glucose homeostasis? Thyroxine stimulates _______ and increases the rates of gastric emptying and intestinal glucose absorption. Patients usually have a normal fasting plasma glucose concentration despite factors that may produce glucose intolerance in thyrotoxic individuals. What is also known as growth hormone inhibiting hormone? Where is somatostatin found? Glyconeogenesis True Somatostatin Gastrointestinal tract, hypothalamus, and Delta cells of the pancreatic islets Somatostatin inhibits secretion of ________ and Glucagon, insulin _______ by the pancreas, thus modulating the reciprocal relationship between the two hormones. What are the primary clinical applications for Immunoassays, isotope dilution mass insulin for the evaluation of patients with spectrometry assay, immunoreactive insulin fasting hypoglycemia? assays What does IDMS stand for? Isotope Dilution Mass Spectrometry What is usually in patients with benign or Proinsulin malignant b-cell tumors of the pancreas? What is primarily used to evaluate fasting C-peptide hypoglycemia and monitor patients response to pancreatic surgery? Measurement of urine C-peptide is useful when B-cell continuous assessment of ______ is desired. Very high concentrations of glucagon are seen Glucagonomas in patients with α-cell tumors of the pancreas called What is low glucagon associated with? Chronic Pancreatitis What are the names of type1 Diabetes Mellitus? Type 1A (Immune medicated diabetes) Type 1B (Idiopathic diabetes) Autoimmune process where there is 80% to Type 1A 90% reduction in the volume of β-cells to induce symptomatic type I diabetes β-cells destruction is due to chromosomal Type 1B abnormality or an unknown cause rather than any autoimmune process What are the most practical markers of beta cell Islet Cell Antibodies (ICA) autoimmunity our circulating antibodies which Insulin Autoantibodies (IAA) have been detected in the serum years before Antibodies to the 65 kDa isoform of glutamic the onset of hyperglycemia: acid decarboxylase Insulinoma-associated antigens (IA-2A and IA-2βA) 4 Chem PPT Flashcards, Unit 4 Zinc Transporter (ZnT8) The human leukocyte antigen (HLA)-DQ and –DR genetics factors Insulin Resistance What are the most important determinants for risk of type I diabetes? What decreased ability of insulin to act on peripheral tissue and also known as syndrome X or the metabolic syndrome? Inability of the pancreas to produce sufficient B-cell dysfunction insulin to compensate for the insulin resistance Chronic complications in diabetes mellitus Diabetes-specific microvascular pathology includes: in the retina, renal glomeruli, and peripheral nerves produces retinopathy, nephropathy, and neuropathy Diabetes is the most frequent cause of? Blindness What disease is the leading cause of diabetes? End stage renal disease What is the major cause of mortality in Myocardial Infarction diabetes? Portable meters for measurement of blood 1. In acute and chronic care facilities (at the glucose concentrations are used in three major patient's bedside and in clinics or settings: hospitals) 2. In physician’s offices 3. By patients at home, work, and school (selfmonitoring of blood glucose - SMBG) What is blood glucose monitoring called based on enzymes, electrodes, or fluorescence implanted subcutaneously? Applies low-level electric current to the skin Spectroscopic measurement of light absorption from subcutaneous tissue The primary substrates for ketone body formation are? What are the 3 kinds of ketone bodies? What is Ketonemia What is Ketonuria Ketonemia and Ketonuria are seen in what two instances? What might cause a decrease in glucose availability? What might cause a decrease in carbohydrate use? Implanted sensors Minimally invasive monitoring Noninvasive monitoring free fatty acids from adipose stores. Acetone β-hydroxybutyrate Acetoacetate Increased concentration of ketones in the blood Increased excretion of ketones in the urine Decreased glucose availability Decreased carbohydrate use Starvation or severe vomiting Diabetes mellitus Glycogen storage disease (von Gierke disease) Alkalosis 5 Chem PPT Flashcards, Unit 4 What are two specimens used to measure ketones? Why are ketones routinely measured in patients with DM? Which ketone body does Gerhardt’s ferric chloride test test for? True or false Acetest is a tablet that turns purple when certain ketones react to it. Acetest tablets contain a mixture of glycine, sodium nitroprusside, disodium phosphate and lactose. Which of these causes the important chemical reaction when in contact with certain ketone bodies? In an acetest tablet, what role does lactose play? In an acetest tablet, what role does disodium phosphate play? Of the three ketones, Acetone, βhydroxybutyrate and Acetoacetate, which does the acetest tablet test for? Why doesn't the acetest test for βhydroxybutyrate? Blood Urine To monitor diabetic ketoacidosis What types of specimen can be used with the acetest? What is the test called that is a modification of the nitroprusside test, in which a reagent strip is used instead of a tablet? Ketostix give a positive result in how many seconds with specimens containing how much acetoacetate in the sample? What test tests for β-hydroxybutyrate? Blood and urine What is the first step in the DiaScreen 1K test? β-hydroxybutyrate in the presence of NAD is converted by β-hydroxybutyrate dehydrogenase to acetoacetate, producing reduced NADH. Diaphorase catalyzes the reduction of nitroblue tetrazolium (NBT) by NADH to produce a purple compound, and its absorbance is read in a special meter that provides a digital readout. the condensation of glucose with the Nterminal valine residue of each β-chain of HbA to form an unstable Schiff base that may dissociate to form a stable ketoamine. The second step in the DiaScreen 1K test once NADH is produced is? How is HbA1c formed? Acetoacetate True Nitroprusside Enhances the color Provides optimum pH for the reaction. Acetoacetate and Acetone (to a lesser extent) β-hydroxybutyrate does not react with nitroprusside Ketostix 15s , 50mg/L DiaScreen 1K 6 Chem PPT Flashcards, Unit 4 True or false True The rate of HbA1c formation is directly proportional to the concentration of glucose in the body. How far in the past does the HbA1c assay detect HbA1c concentration represents integrated glucose values? values for glucose over the preceding 8-12 weeks. An HbA1c value of ≥ 6.5% is considered to be Diabetes the decision point used for the diagnosis of? What HbA1c value range indicates individuals from 5.7% to 6.4% at high risk of developing diabetes? What is the “normal” reference interval for 4%-5.6% HbA1c? True or false True HBA1c is accepted to be an alternative to glucose for screening for diabetes. What test is is firmly established as an index of HbA1c long-term blood glucose concentration and a measure of the risk for developing microvascular complications in patients with diabetes. In patients without diabetes, how is HbA1c HBA1c is directly related to risk of used? cardiovascular disease How is HbA1c used to monitor patients who are It is recommended that HbA1c should be compliant to the diabetic lifestyle, diet, exercise routinely monitored at least every 6 months in etc.? patients meeting treatment goals and who have stable glycemic control. What are the three general methods for HbA1c Methods based on Charge differences. determination? Methods based on structural differences. Methods based on chemical analysis. What are the HbA1c methods based on charge Ion Exchange Chromatography differences? HPLC Electrophoresis Isoelectric focusing What are the HbA1c methods based on Affinity Chromatography structural differences? Immunoassays What are the HbA1c methods based on Photometry chemical analysis? spectrophotometry Is fasting required for the HbA1c test? No What type of tube/anticoagulant should be used Lavender EDTA, Gray oxalate or fluoride for the HbA1c test? Fructosamine is? the generic name for plasma protein ketoamines, specifically glycated serum albumin. How far in the past does glycated albumin 2-3 weeks measure glucose control? 7 Chem PPT Flashcards, Unit 4 When is glycated albumin most useful? What are three test methods used to measure glycated albumin? What refers to an excretion rate of albumin greater than normal but less than that detectable by routine dipsticks methods? What is the excretion rate? What does a UAE rate of greater than 200µg/min indicate? What does urinary albumin excretion precede and is highly indicative of? What else can UAE indicate? What physiological factors can increase UAE? When should sample for UAE not be collected? What are some examples of acceptable specimens? At what temperature is urine stored and for how long is it stbale? At what temperature does albumin concentration decrease by 0.27 % per day? What temperature should refrigerated urine samples be allowed to reach before analysis? How many specimens should be assayed and why? Useful in conditions where HBA1c is of little value, such as I patients with hemoglobin variants that are associated with decreased erythrocyte life span. 1. Affinity Chromatography 2. High Performance Liquid Chromatography (HPLC) 3. Photometric and Spectrophotometry High albuminuria (formerly known as microalbuminuria). 20 to 200 µg/min (30 to 300 mg/24hours Overt diabetic nephropathy 1) Diabetic nephropathy 2) End-stage renal disease 3) Cardiovascular mortality Total mortality in patients with diabetes It identifies a group of people without diabetes who are at risk for coronary artery disease 1) Exercise Posture and diuresis 1) After exertion 2) In the presence of infection (UTI) 3) During acute illness 4) Immediately after surgery After an acute fluid load 1) 24 hour collection 2) Overnight (8-12 hours times) 3) 1-2 hour timed collection First morning sample Urine should be stored at 4 degrees Celsius after collection. It is stable for 1 week at 4 degrees Celsius and for at least 5 months at 80 degrees Celsius. Urine should be stored at 4 degrees Celsius after collection. It is stable for 1 week at 4 degrees Celsius and for at least 5 months at -80 degrees Celsius. -20 degrees celsius 10 degrees Celsius At least 3 separate specimens, collected on different days, should be assayed because of high intraindividual variation and diurnal 8 Chem PPT Flashcards, Unit 4 What does diagnosis require? What testing methods are used? What are some examples of quantitative methods used to screen UAE? What are the two most common cardiovascular disorders that rely on a biochemical diagnosis? What are the measurement of cardiac biomarkers useful in diagnosing and detecting? What is the most serious form of ischemic disease? What is an acute myocardial infarction? When does this occur? What is the result when this happens? What is the condition marked by severe pain in the chest, often also spreading to the shoulders, arms and neck caused by an inadequate blood supply to the heart? What is an angina that occurs unpredictable or suddenly increased in severity of frequency? What is a sudden cardiac disorder that varies from angina to unstable angina and to myocardial infarction? What is the weight of the average human heart? What is the sac that encloses the heart? variation (50% to 100% higher during the day) Increased UAE in at least 2 of 3 test measured within a 3-6 month period 1) Test strips are semi-quantitative assays used for screening Quantitative methods 1) RIA 2) ELISA 3) Radial Immunodiffusion Immunoturbidimetry 1) Acute ischemic disease (acute myocardial infarction) Heart failure (congestive heart failure) 1) Cardiac disease 2) Cardiac disorders 3) Detecting the risk of developing cardiac disorders 4) Monitoring the disorder Predicting the response of a disorder to a treatment Acute myocardial infarction (AMI) It is an acute infarction (obstruction of circulation) of the heart muscle occurring during the period when circulation to a region of the heart is obstructed and necrosis is occurring It occurs when there is an imbalance between supply and demand for oxygen in the myocardium This can result in injury and to eventual death of muscle cells. When blood supply is blocked for more than a few minutes, most of the muscle cells die. Angina Unstable angina Acute coronary syndrome 325 grams in men and 275 grams in women Pericardium 9 Chem PPT Flashcards, Unit 4 What are the 3 layers of the cardiac wall? What are the 4 chambers of the heart? A cardiac cycle consists of what two intervals? What is systolic pressure? What is diastolic pressure? What is an electrocardiogram (ECG)? What is an ECG used to identify? What are an ECG’s three major components What is acute coronary syndrome? What is the major cause of acute coronary syndrome? What is atherosclerosis? Atherosclerosis, the abnormal blood flow through the narrowing of an artery is caused by what yellowish substance? Detection of rise and/or fall of cardiac biomarkers (preferably troponin) above the 99th % of the upper reference limit, together with evidence of ischemic symptoms with at least one of the fallowing symptoms of ECG changes of ischemia changes or new left bundle branch block, development of pathologic Q waves on the ECG, identification of an intracoronary thrombus by angiography or autopsy is criteria for the definition of what? 4 cardiac markers for the diagnosis of acute myocardial infarction are? 1) Epicardium (outermost layer where coronary arteries are found) 2) Middle layer 3) Endocardium (innermost layer most susceptible to myocardial ischemia) Upper chambers (right and left atria) Lower chambers (right and left ventricles) Systolic and diastolic The blood pressure in the aorta is about 120 mm Hg The blood pressure falls to about 70 mm Hg It records changes in electrical potential and is a graphic tracing of the variation in electrical potential caused by the excitation of the heart muscles. Used to identify the anatomic, metabolic, ionic, and hemodynamic changes in the heart 1) Atrial depolarization (p wave) 2) Ventricular depolarization (QRS complex) Repolarization (ST segment and T wave) Includes individuals who have a variety of forms of unstable ischemic heart disease Athersosclerosis A diseased caused by plaque (a deposit of fatty material) formed in the inner lining of the coronary arteries that feed the surface of the heart, contributing to significant narrowing of the artery’s lumen. Atherosclerotic Plaque Myocardial Infarction AST, SGOT - aspartate aminotransferase LD - lactate dehydrogenase CK - total creatine kinase 10 Chem PPT Flashcards, Unit 4 A condition in which the heart has lost the ability to pump enough blood to the body’s tissue? As a result to CHF, the _____ may respond by causing the body to retain fluid (water) and salt. A common cause of CHF; a disease of the arteries that supply blood and oxygen to the heart causes decreased blood flow to the heart muscles. The heart becomes starved for oxygen and nutrients if the arteries become blocked or severed narrowed. This disease is known as? A common cause of CHF include damage to the heart muscle from causes other than artery blood flow problems such as from infections, alcohol or drug abuse is known as? These are substances that are released onto the blood when the heart is damaged or stressed. Measurements of cardiac biomarkers are used to help diagnose ___ ____ ____and ___ ___, conditions associated with insufficient blood flow to the heart as well as CHF. These are specific proteins found in cardiac muscles and are measured in the diagnosis of myocardial infarction. Three troponin subunits form a complex that regulate the interaction of actin and myosin and thus regulate cardiac contractions are? a-hydroxybutyrate Congestive Heart Failure (CHF) kidneys Coronary artery disease (CAD) Cardiomyopathy Cardiac Biomarkers acute coronary syndrome (ACS) and cardiac ischemia cTns Troponin T (the tropomyosin-binding component) Troponin I (The inhibitory component) Troponin C (the calcium-binding component) Cardiac troponin __ and Cardiac troponin __ are Cardiac troponin I (cTnI) the two main types of troponin used as cardiac and biomarkers. Cardiac troponin T (cTnT) Trponins are localized primarily (94%-97%) in myofibrils the ____ with smaller cytoplasmic fraction. In general, what is the technique of choice for Immunoassay measuring cTns? The laboratory should perform biomarkers 1 hour 30 minutes testing with a maximum turnaround time (TAT) of how long? What term is defines as the time from blood Turnaround time (TAT) collection to the reporting of results to the provider? What type of blood specimen appears to be the Anticoagulated whole blood or plasma optimal specimen for rapid processing and testing? What two blood tube collection additives EDTA and Heparin 11 Chem PPT Flashcards, Unit 4 interfere with troponin antibody-binding affinity? This type of cardiac testing is detected by a 32amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). The release of this test is modulated by calcium ions. The 3 major circulating forms of BNP are? What does a normal level of either BNP or NTproBNP rule out in am emergency setting? True or False An elevated BNP or NT-proBNP should never be used to rule in acute or chronic heart failure in emergency settings due to lack of specificity What can be used for screening and prognosis of heart failure? BNP or NTproBNP are typically increased in what kind of patients? BNP accurately reflects what? What is the half-life of BNP? What is the half life of NT-proBNP? How are the concentrations of BNP and NTproBNP measured? What is the acceptable specimen used for BNP? What is the acceptable specimen used for NTproBNP Where is CK enzyme present? (3) Name the 3 isoemzymes of CK Which CK isoenzyme is the dominant form in the brain and smooth muscle? Which CK isoenzyme is sometimes called the cardiac isoenzyme because 10%- 20% of total CK activity in myocardium is from CK-MB? Which CK isoenzyme is predominant in both heart and skeletal muscle? What is CK-Mt Brain Natriuretic Peptide (BNP) 1) NT-pro BNP (N-terminal protion or fragment of proBNP) 2) proBNP 3) BNP (C-terminal part of proBNP and the physiological active hormone Acute heart failure True Either BNP or NT-proBNP Patients with left ventricular dysfunction, with or without symptoms Current ventricular status 20 minutes 1-2 hours By immunoassays EDTA-anticoagulated whole blood or plasma in plastic blood collection tube Serum, heparin-plasma, EDTA plasma collected in either glass or plastic Heart muscle, skeletal muscle and the brain CK1 or CKBB CK2 or CKMB CK3 of CKBB CK-Mt CK1 or CKBB CK2 or CKMB CK3 or CKMM Mitochondrial isoenzyme 12 Chem PPT Flashcards, Unit 4 What is C-reactive protein? What does it mean when concentrations of Creactive protein fall below those seen in infection but above healthy values? What is an oxygen binding protein of cardiac and skeletal muscle? Myoglobin levels increase before CK2 after what? (Increases/decreases) in serum myoglobin occur after trauma to skeletal or cardiac muscle as in crush injuries or AMI Why are false-negative results of myoglobin seen in patients after a few hours? True or False Kidneys play a central role in homeostatic mechanisms Fill in the blank: Kidneys filter the _______ and excrete the end products of the body metabolism in the form of ________. The kidneys regulate the concentrations of which ions? True or False? Kidneys do not function to produce hormones What is the functional unit of the kidney? Name all the parts of the nephron What is the outer region of the kidney called? What is the inner region of the kidney called? Where is the glomerular capillary network formed? What does Pars convolute become? What does the collecting ducts form? What does the ducts of Bellini drain into? What is glomerulus formed by? What is the Juxtaglomerular Apparatus? What does it do? What does it generate? How does vasoconstriction work? What do Anterior and posterior renal artery An acute phase reactant initially developed to evaluate patients with infection They are shown as biomarkers of arteriosclerotic process Myoglobin AMI Increases Because increases of serum concentrations of myoglobin are cleared rapidly True Blood; Urine Hydrogen, sodium, potassium, phosphate, and other ions in the ECF False The nephron Glomerulus, proximal tubule, loop of Henle, distal tubule, and collecting duct Cortex Medulla On the basement membrane Pars recta Ducts of Bellini The renal calyx Specialized network of capillaries on basement membrane. Area of specialization at area of loop of Henle and Bowman's capsule Maintains systemic blood pressure by regulating blood volume and sodium concentration Generates angiotensin acts to increase release of antidiuretic hormone arterioles and then capillaries 13 Chem PPT Flashcards, Unit 4 divide into ? What do capillaries form? Efferent arteriole merges with what? Renal veins emerge into what? Kidneys receive how much of cardiac output in adults? What are the 3 functions of the kidneys? Urine passes from kidneys to? Characteristics of healthy urine? Urination (or micturition) is adequate at? Oliguria (<400 ml/day) is? What does oliguria result from? What is Anuria? What does anuria result from? Polyuria is what? What causes polyuria? What is Nocturia? What types of homeostasis is regulated in kidneys? How is electrolyte homeostasis maintained? How is water homeostasis maintained? What hormones are produced? Secondary endocrine function is what? Three physiological functions of kidneys? What does GFR measure? What is useful about measuring GFR? efferent arteriole renal venules to form renal veins inferior vena cava about 25% Excretion, Homeostatic regulation, Endocrine Ureters, to bladder, exits urethra sterile, clear, amber, slightly acidic about 500 mL per day decrease in the normal daily urine output commonly accompanies states of dehydration such as vomiting, diarrhea, perspiration or severe burns Absence of urine results from serious damage to the kidneys or from a decrease in the flow of blood to the kidneys increase in the normal daily urine output, (>3,000 ml/day) seen in diabetes mellitus and diabetes insipidus induced with diuretics, caffeine or alcohol consumption increase in the excretion of urine at night Electrolyte and water. Reabsorption in proximal convoluted tubule Bicarbonate, phosphate, high-threshold substances, uric acid 70% reabsorbed in proximal tubule 5% in loop of Henle 10% in distal tubule Remainder in collecting ducts Erythropoietin, Prostaglandins and thromboxanes, Renin, and 1,25(OH2) vitamin D3 (site of action for hormones produced or activated elsewhere) Glomerular Filtration Rate (GFR), Renal Blood Flow Glomerular Permeability functional capacity of the kidneys and indicative of the number of functioning nephrons. targeting treatment, monitoring progression, 14 Chem PPT Flashcards, Unit 4 The renal clearance of a substance is defined as what? For a substance(s) or marker(s) to be used to measure renal clearance, it must be what 7 things? What is the concept of the renal clearance of a substance? predicting when renal replacement therapy (RRT) will be required, and as a guide to dosage of drugs excreted by the kidneys to prevent potential drug toxicity. as "the volume of plasma from which the substance is completely cleared by the kidneys per unit of time". 1. In stable concentration in the plasma 2. Physiologically inert 3. Freely filtered at the glomerulus 4. Neither secreted 5. Neither reabsorbed 6. Neither synthesized 7. Not metabolized by the kidney Clearance (ml/min) = U/P x V (mL/min) x 1.73/A What are U,P, V, 1.73, and A stand for? U= concentration of the substance in urine P = concentration of substance in plasma (blood) V = total volume of urine excreted in 24 hrs converted to mL/min 1.73 = body surface area in square meters A = body surface of patient obtained from patient’s height and weight (nomogram) What markers have been used to estimate clearance? A variety of endogenous and exogenous markers. Endogenous markers: Creatinine concentration Low–molecular weight proteins (Cystatin C) Exogenous markers: Inulin Iohexol Radiopharmaceuticals 51Cr-ethylenediaminetetraacetic acid (EDTA) 99mTc-diethylenetriaminepentaacetic acid (DTPA) 125 I-iothalamate What urinary protein loss is defined? Increased urinary protein loss (proteinuria) results from any increase in the filtered load, increased circulating concentration of low molecular weight proteins, or decrease in reabsorptive capacity It is less than 150 mg /24 hours which is How is the normal urinary total protein loss? 15 Chem PPT Flashcards, Unit 4 What primary part is the predominant protein in urine in the majority of kidney diseases and is accurately and specifically measured using immunoassay techniques? How is progression of kidney disease leading to loss of function and ultimately to kidney failure? How many parts pathophysiology of kidney disease are? What is the definition of Acute kidney injury (AKI)? How Chronic kidney disease (CKD) is defined? What markers used to identify CKD? What is sevenfold to tenfold greater in patients with CKD? What is characterized as elevated total or lowdensity lipoprotein (LDL) cholesterol levels, and elevated triglycerides. What is is also affected in CKD, leading to "adynamic" bone diseases. mostly albumin (50% to 60%) Albumin These are: Early inflammation Accumulation and deposition of extracellular matrix Tubulointerstitial fibrosis Tubular atrophy Glomerulosclerosis (scarring) Diagnosis and screening for kidney disease Urinalysis Proteinuria Hematuria a symptoms or physical sign systemic disease with the known renal involvement like diabetes mellitus 1. Increase of plasma creatinine by ≥ 0.3 mg/dL (26 µmol/L) within 48 hours 2. Increase in plasma creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days 3. Reduction in urine output (documented oliguria < 0.5 mL/kg/hr for more than 6 hours Is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health These are plasma creatinine, estimated GFR and measured creatinine. Lowering blood pressure and reduction of proteinuria have been shown to decrease the progression of CKD The incidence of cardiovascular disease It is Dyslipidemia in CKD Calcium and phosphate metabolism 16 Chem PPT Flashcards, Unit 4 How Adynamic bone is defined? How the classic signs of uremia? bone is associated with low PTH concentration, abnormal calcium balance, hyperphosphatemia, acidosis and the use of high doses of vitamin D analogs.Due to the predominant loss of peritubular fibroblast (specialized cells that produce collagen) within the renal cortex that synthesize erythropoietin, thus causing anemia The symptoms are progressive weakness and easy fatigue, loss of appetite followed by nausea and vomiting, muscle wasting, tremors, abnormal mental function, frequent but shallow respirations and metabolic acidosis. What are the most characteristic laboratory findings in Uremic syndrome? The most characteristic laboratory findings are increased concentrations of nitrogenous compounds in plasma such as urea and creatinine, as a result of reduced GFR and decreased tubular function. How retention of urea and creatinine and of metabolic acids is followed? Retention of urea and creatinine and of metabolic acids is followed by progressive hyperphosphatemia, hypocalcemia and potentially dangerous hyperkalemia Kidneys fail to maintain adequate excretory, regulatory, and endocrine function.At least 90 organic compounds are retained in urea What are another diseases of kidney? These are diabetic nephropathy and hypertensive nephropathy. How is diabetic nephropathy defined? It is a clinical diagnosis based on the finding of proteinuria (albuminuria) in a patient with diabetes It is the most common cause of end stage renal disease (ESRD) What is hypertensive nephropathy Hypertensive nephropathy considered another accelerating force in the development of ESRD. What are Glomerular diseases? • Glomerular diseases 17 Chem PPT Flashcards, Unit 4 • Immunoglobulin A nephropathy • Rapidly progressive glomerulonephritis • Acute nephritic syndrome • Nephrotic syndrome What are Interstitial nephritis diseases? • What is the Polycistic kindney disease? What causes Toxic nephropathy? What is Obstructive uropathy? What are the different diseases of the kidney? What is Dialysis of the kidney? Interstitial nephritis • Caused by a variety of chemical, bacterial, and immunological injuries to the kidney • Polycystic kidney disease • Is the most common inherited kidney disease presented by hypertension and gross hematuria. • Toxic nephropathy • Caused by a wide variety of nephrotoxins present in the environment like cadmium and lead. • Obstructive uropathy Benign prostatic hypertrophy (BPH) is one of the most common type. • Tubular diseases • Renal tubular acidoses • Inherited tubulopathies • Diuretics • Diabetes insipidus • Renal calculi • Prostaglandins and NSAIDs in kidney disease • Monoclonal light chains and kidney disease • • Dialysis Is the process of separating macromolecules from ions and 18 Chem PPT Flashcards, Unit 4 low molecular weight compounds in solution by the difference in their rates of diffusion through a semipermeable membrane. Explain dialysis procedures? Crystalloids (aqueous solutions of mineral salt) passed readily through this membrane, but larger substances (colloids) passed very slowly or not at all. • Dialysis procedures include: • Hemodialysis HD) • Is the most common method used to treat advanced and permanent kidney failure by connecting the patient to a hemodialyzer into which their blood flows. • Hemodiafiltration (HDF) • Is a method of treatment that combines hemodialysis and hemofiltration that yields more urea clearance than hemodialysis alone. What is Peritoneal dialysis (PD)? What is Kidney transplantation and • Peritoneal dialysis (PD) • Type of dialysis in which dialysate is introduced into the patient's peritoneal cavity and the peritoneum employed as the dialysis membrane • Kidney transplantation 19 Chem PPT Flashcards, Unit 4 how is it successful? What are the criterias for kidney transplants? • Is the most effective form of renal replacement therapy (RRT) in terms of long-term survival and quality of life. • Successful transplantation requires: • 1. Preoperative assessment • 2. Postoperative assessment • 3. Therapeutic drug management • Preoperative assessment • Criteria for acceptance include: • candidates should not be obese (body mass index (BMI) should be less than 40 kg/m²) • should NOT have severe chronic lung disease, inoperable ischemic heart disease, active infective liver or immunological disease, chronic infection like tuberculosis, pre-existing malignancy or lower urinary tract 20 Chem PPT Flashcards, Unit 4 dysfunction How is total body water (TBW) distributed? How is the ECF subdivided? What is the average adult blood volume and plasma volune? What are some factors that influence water and electrolytes in the human body? How much water do adult humans need to intake? What are some primary cationic electrolytes? What are some primary anionic electrolytes? What are the major ions in the ECF? What are the major ions in the ICF? What causes active transport? What is an example of an active transport system in the human body? Define active transport? Two- thirds of total body water(TBW) is distributed into intracellular fluid (ICF) compartment, and one third into the extracellular fluid (ECF) compartment. These compartments are separated by plasma membrane. - Interstitial fluid compartment (≈75% of ECF) Intravascular fluid compartment (≈25% of ECF): these fluid compartments are separated by capillary endothelium The average adult has ≈ 5.0 L blood volume (intravascular compartment) and a plasma volume of ≈ 3.0 L when the hematocrit is ≈40%. Factors that influence water and electrolyte requirements include activity of the individual, environment, and disease. On average, an adult must take in ≈ 1.5 to 2.0 L of water daily to maintain fluid balance Na+, K+, Ca2+, and Mg2+ Cl–, HCO3–, HPO42–, SO42–, organic ions, and negatively charged proteins Na+, Cl–, and HCO3– K+, Mg2+, organic phosphates, and protein - The unequal distribution of ions is due to active transport of Na+ from inside to outside the cell against an electrochemical gradient. ATP which is present in most cell membranes is required for active transport. Na + /K + -ATPase, an ubiquitous Na-H exchanger (often referred to as an antiporter), actively pumps H+ out of the ICF in exchange for Na+. This is critical for maintaining intracellular pH homeostasis. - Can be defined as a process in which a molecule is carried from a region of lower concentration to a region of higher concentration against the concentration gradient. Because of the resistance which occurs during this process, it needs energy. It is thus named 21 Chem PPT Flashcards, Unit 4 as "active“ transport because of its one vital ingredient, which is the energy that is required for this process. Define passive transport? - Can be defined as a process in which a molecule is carried from a higher concentration to a lower concentration along the concentration gradient and therefore, it faces no resistance. Because of the lack of persistence, passive transport requires no energy for this purpose to take place and hence the name "passive“ transport. What is the difference between an active and a - The main difference between active passive transport? transport and passive transport is the fact that active transport needs energy which is known as Adenosine Triphosphate (ATP). - Active transport requires energy whereas passive transport does not. Active transport involves the carrying of a molecule or a solute against a concentration gradient; Passive transport involves the carrying of a molecule or a solute along the concentration gradient. What role does sodium have in kidney function? • Kidney function • Proximal convoluted tubules • 70% to 80% of filtered sodium is actively reabsorbed • water and chloride passively reabsorbed • Descending loop of Henle • water but not electrolytes is passively absorbed • Ascending loop of Henle • chloride is actively reabsorbed with the sodium following • Distal convoluted tubules secretion of aldosterone, renin and antidiuretic hormone What role does sodium have in hyponatremia? - Defined as a decrease plasma sodium concentration (<130 to 135 mmol/L) - Hypo-osmotic hyponatremia: Hyponatremia characterized by low 22 Chem PPT Flashcards, Unit 4 What role does sodium have in hyperosmotic hyponatremia? What role does sodium have in isomotic hyponatremia? What role does sodium have in hypernatremia? What role does sodium have in Hypovolemic hypernatremia? What is Normovolemic hypernatremia? What role does potassium have in Hypokalemia? plasma sodium concentration, low calculated or measured osmolality. - Depletional hyponatremia: Hyponatremia due to excess loss of sodium Dilutional hyponatremia: Hyponatremia due to increased ECF volume - Hyponatremia that occurs in the presence of increased quantities of others solutes in the ECF as a result of an extracellular shift of water or on intracellular shift of Na+ to maintain osmotic balance between ECF and ICF compartments. The most common type is seen in severe hyperglycemia. A pseudohyponatremia caused by an electrolyte exclusion effect characterized by decrease in measured Na+ concentration but with normal plasma osmolality, glucose and urea levels. - Increase plasma sodium concentration (>150 mmol/L) Hypovolemic hypernatremia: Hypernatremia characterized by decrease ECF caused by renal or extra-renal loss of hypo-osmotic fluid, leading to dehydration. - Hypernatremia in the presence of excess total body water indicating a net gain of water and sodium, with sodium gain in excess of water. Commonly seen in hospital patients receiving hypertonic saline or sodium bicarbonate. Hypernatremia in the presence of normal ECF volume seen in diabetes insipidus. - Decrease in extracellular potassium (<3.5 mmol/L) either due to redistribution of extracellular K+ into ICF, or true K+ deficits, caused by decreased intake or loss of potassium rich body fluids - characterized by muscle weakness, irritability and paralysis. Concentrations less than 3 mmol/L are often associated with marked neuromuscular symptoms. 23 Chem PPT Flashcards, Unit 4 What role does potassium have in Hyperkalemia? Following are characteristics of what type of electrolyte disorder? Decreased chloride levels causes of hypokalemia will parallel causes of hyponatremia respiratory acidosis, accompanied by increased HCO3-, is another common cause of decreased Cl with normal Na Hyperchloremia is defined as? Following are characteristics of what type of electrolyte disorder? similar to increased Na+ concentrations, as seen in dehydration, prolonged diarrhea with loss of sodium bicarbonate, diabetes insipidus, and overtreatment with normal saline solutions Hyperchloremia is seen in respiratory alkalosis or respiratory acidosis? How much of the total carbon dioxide of plasma is made up of bicarbonate ions? What is the characteristic of acid-base imbalances? What is the total carbon dioxide (CO2) content of plasma consist of? What is the normal blood PH? Alkalemia (alklaosis) is defined as? True or False Acids - are chemical substances that donate protons (H+ ions) True or False Bases - are chemical substances that accept protons PH of a solution is defined as? At lower concentrations, tachycardia and cardiac conduction defects are apparent by ECG (flattened T waves) and has been known to lead to cardiac arrest. - Increased plasma K+ (>5.0 mmol/L) which may be caused by redistribution, increased intake, or increased retention pre-analytical conditions such as hemolysis, thrombocytosis, and leukocytosis have been known to cause marked pseudohyperkalemia Hypochloremia Increased Chloride levels Hyperchloremia Seen in respiratory alkalosis because of renal compensation for excreting HCO3-. Bicarbonate ions makeup all but ≈2 mmol/L of the total carbon dioxide of plasma Alterations in HCO3- and CO2 dissolved in plasma Carbon dioxide dissolved in an aqueous solution (dCO2), CO3 loosely bound to amine groups in proteins (carbamino compon), HCO3-, and very small quantities of CO32ions and carbonic acid acid (H2CO3). 7.35 – 7.45 an arterial blood pH > 7.45 True True negative logarithm of hydrogen ion activity 24 Chem PPT Flashcards, Unit 4 What is the average pH of blood (7.40) corresponds to? What PK is defined as? What is PK values for acids? What is PK values for bases? What is the most important buffering system in the body? What is the effectiveness of Bicarbonate/carbonic acid buffer system? ----------are able to increase or decrease the rate of reclamation of bicarbonate from the -----------? What is the normal bicarbonate/dCO2 ratio? What is the ratio (cHPO42-/cH2PO4-) In Phosphate buffer system At the plasma pH of 7.4? Name the buffer system which the total concentration of it is in both erythrocytes and plasma accounts for about 5% of the nonbicarbonate buffer value of plasma? What is the form of organic phosphate in phosphate buffer system? In phosphate buffer system----------- accounts for about 16% of the non-bicarbonate buffer value off erythrocytes. What is the major part of the non-bicarbonate buffers of erythrocyte fluid? What is the most important buffer groups of protein in the physiological pH range? What protein accounts for the greatest portion (>90%) of the non-bicarbonate buffer value of plasma? What are four conditions associated with Abnormal Acid-Base Status and Abnormal Electrolyte Composition of the Blood? Following are characteristics of what type of acid base condition? production of organic acids that exceeds the rate of elimination (e.g. production of a set the (pH = - log aH+) a hydrogen ion concentration of 40 nmol/L Is the pH at which an acid is half dissociated, existing as equal proportions of acid and conjugate base. Acids have pK values <7.0 Bases have pK values > 7.0 Bicarbonate/carbonic acid buffer system is based on the fact that the lungs are able to readily dispose of or retain CO2 renal tubules- glomerular filtrate 20:1 4:1 (pK=6.8) Phosphate buffer system 2,3-diphosphoglycerate (present in erythrocytes in a concentration of about 4.5 mmol/L), organic phosphate hemoglobin imidazole groups of histidine (pK = 7.3) albumin Metabolic acidosis (primary bicarbonate deficit) Metabolic alkalosis (primary bicarbonate excess) Respiratory acidosis Respiratory alkalosis Metabolic Acidosis 25 Chem PPT Flashcards, Unit 4 acetic acid and β- hydroxybutyric acid in diabetes ketoacidosis and of lactic acid in lactic acidosis) Following are characteristics of what type of acid base condition? reduced excretion of acids (H+) ask occurs in renal failure and some renal tubular acidosis, resulting in the accumulation of acid that consumes bicarbonate Following are characteristics of what type of acid base condition? excessive loss of bicarbonate due to increased renal excretion (decreased tubular reclamation) or excessive loss of duodenal fluid (as in diarrhea) In Metabolic Acidosis the ratio of cHCO3/cCO2 is decreased or increased? What is the resulting drop in pH in Metabolic Acidosis? Anion gap is increased or decreased in Metabolic Acidosis? What is the first indication of a metabolic acidosis? What test should be used for assessing the presence of an elevated anion gap? What is Respiratory compensatory mechanism in metabolic acidosis? What is Kussmaul breathing? When Metabolic Alkalosis occurs? In the Metabolic Alkalosis the ratio of cHCO3/cCO2 is increased or decreased? What is Respiratory compensatory mechanism in metabolic alkalosis? What are some compensatory mechanisms in metabolic alkalosis? Metabolic Acidosis Metabolic Acidosis Decreased because of the primary decrease in bicarbonate. The resulting drop in pH stimulates respiratory compensation via hyperventilation, which lowers PCO2 and thereby increases the pH Increased the presence of an elevated anion gap should be assessed in the electrolyte profiles of all patients The decrease in pH stimulates hyperventilation (Kussmaul respiration) which results in: 1. The elimination of carbonic acid as CO2 2. A decrease in PCO2 (hypocapnia) 3. A decrease in cdCO2 Is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also kidney failure 1. Excess base is added to the system 2. Base eliminations decreased 3. Acid-rich fluids are lost increased because of the primary increase in bicarbonate The patient will hypoventilate to raise PCO2, thereby lowering the pH stored normal It will include both respiratory and renal compensation. The increase in pH depresses 26 Chem PPT Flashcards, Unit 4 What is respiratory acidosis? Does respiratory acidosis occur only through decreased elimination of CO2? What is the most common cause of respiratory acidosis? What may be another cause of respiratory acidosis? What are some compensatory mechanisms in respiratory acidosis? What causes respiratory alkalosis? Is the basic cause of respiratory alkalosis is excess elimination of acid via the respiratory about? What does excessive elimination of carbon dioxide cause? What is the first stage of compensatory mechanism of respiratory alkalosis? What is the second stage of compensatory mechanism of respiratory alkalosis? the respiratory center, causing retention of carbon dioxide (hypercapnia), which in turn causes an increase in cH2CO3 and cdCO2. The kidneys respond to the state of alkalosis by decreased Na+-H+ exchange, decreased formation of ammonia and decreased reclamation of bicarbonate Any condition that decreases elimination of carbon dioxide through the lungs results in an increase in PCO2 (hypercapnia) and dCO2 (respiratory acidosis). Yes Chronic Obstructive Pulmonary Disease (COPD) Rebreathing , or breathing air high in CO2 content may also cause a high PCO2 The increased PCO2 stimulates the respiratory center, resulting in an increase pulmonary rate and depth of respiration. Elimination of carbon dioxide through the lungs results in a decrease in cdCO2; thus the ratio of cHCO3/cdCO2 and pH approach normal.The kidneys respond similarly to the way that they respond to metabolic acidosis and namely, with increased Na+-H+ exchange, increased ammonia formation and increased reclamation of bicarbonate. A decrease in PCO2 (hypocapnia) and the resulting primary deficit in cdCO2 (respiratory alkalosis) are caused by an increased rate and/or depth of respiration. Yes Excessive elimination of carbon dioxide reduces the PCO2 and causes an increase in the cHCO3-/cdCO2 ratio. In the first stage, erythrocyte and tissue buffers provide H+ ions that consume a small amount of HCO3-. The second stage becomes operational in prolonged respiratory alkalosis and the kidneys respond by decreasing Na +-H + exchange, decreasing formation of ammonia and decreasing reclamation of bicarbonate. 27 Chem PPT Flashcards, Unit 4 What is Diabetes Mellitus? What are some life-threatening episodes? What are some complications due to DM? About how many cases are DM Type 1? What are some abrupt symptoms of DM Type 1? What is the cause of DM Type 1? What are patients with DM Type 1 dependent on? Do most patients with DM Type 1 have antibodies? When is the peak/main onset of DM Type 1? About how many cases are DM Type 2? Do most patients with DM Type 2 show any symptoms? Are patients with DM Type 1 dependent on anything? How are insulin levels in a DM Type 2 patient? D most individuals with DM Type 2 have impaired insulin action? How is DM Type 2 characterized? A group of metabolic disorders of carbohydrate metabolism in which glucose is underuse leading to hyperglycemia Life-threatening episodes: ketoacidosis, hyperosmolar coma Complications: diabetic retinopathy (blindness), diabetic nephropathy (renal failure), neuropathy (nerve damage), atherosclerosis About 5% to 10% Abrupt onset of symptoms such as polyuria, polydipsia, and rapid weight loss. They have insulinopenia (a deficiency of insulin) caused by loss of pancreatic islet β-cells Dependent on insulin to sustain life and prevent ketosis Most patients have antibodies that identify an autoimmune process Peak incidence occurs in childhood and adolescence (before the age of 18), but onset in the remainder may occur at any age About 90% of cases Patients have minimal symptoms, and are not prone to ketosis Patients are not dependent on insulin to sustain life and to prevent ketonuria Insulin concentrations may be normal, decreased, or increased. Yes This form of diabetes is characterized by receptor deficiency. What is DM Type 2 commonly associated with? Commonly associated with obesity; can be improved by weight loss What are some treatments for DM type 2? Individuals with the disease may require dietary manipulation, oral hypoglycemic agents, or insulin to control hyperglycemia. When is the peak/main onset of DM Type 2? Peak incidence after 40 years of age, but it may occur in younger people What are some underlying causes of Genetic defects of β-cell function, genetic hyperglycemia? defects in insulin action, exocrine pancreas disease, and endocrinopathies (Cushing syndrome, acromegaly, glucogonoma) What is the functional anatomic unit of the The lobule liver? 28 Chem PPT Flashcards, Unit 4 What are Kupffer cells? What do Kupffer cells contain, and what function do they serve? What is the main site for clearance of antigenantibody complexes from the blood? What are the major functioning cells in the liver? What are they responsible for? What is the site of oxidative phosphorylation and energy production? What is the site of protein synthesis? What does the smooth ER contain? What enzyme is contained in lysozomes? What does it act as? What are two substances secreted by the Golgi apparatus? How is hepatic excretory function measured in the liver? What are drug metabolic tests used for in assessing hepatic excretory function? What plasma proteins are used in assessing hepatic protein synthesis function? Besides proteins, what other organic compound is used in assessing hepatic synthetic function? When checking ammonia metabolism in hepatic metabolic function what ailments are being checked for? What are xenobiotics? What are some clinical manifestations of liver disease? What is another name for jaundice? What is jaundice characterized by? How does portal hypertension occur? Macrophages that live in the liver Lysosomes which break down phagocytized bacteria. Lysosomes in Kupffer cells. Hepatocytes, which are responsible for most of its metabolic and synthetic functions Mitochondria Rough ER Microsomes involved in drug and toxn metabolism and cholesterol and bile acid synthesis. Hydrolytic enzymes which act as scavengers. Bile acids and albumin. Measurement of plasma concentrations of endogenously produced compounds such as bilirubin, and less commonly used bile acids. Used as markers of function in liver transplants and in advanced liver disease. Plasma proteins such as albumin, transthyretin, immunoglobulins, ceruloplasmin, α1-antitrypsin, and αfetoprotein and coagulation proteins. Urea Reye syndrome and hepatic encephalopathy Foreign substances that are cleared and metabolized by the liver such as bromsulfonphthalein (BSP), indocyanine green (ICG), aminopyrine, caffeine, lidocaine and stain rose bengal. Jaundice, portal hypertension, Bleeding esophageal varices, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome. Icterus A yellow appearance of the skin, mucous membranes and sclera caused by bilirubin deposits. When there is obstruction to portal flow anywhere along its course 29 Chem PPT Flashcards, Unit 4 How are the causes of obstruction leading to portal hypertension classified? Which classification is the most common cause of portal hypertension? Which classification is also known as BuddChiari syndrome? Which coagulation factors are synthesized in the liver and measured by PT (prothrombin time)? What may also cause an increase in PT in cholestasis? What does a disorder of fibrinogen lead to in both acute and chronic liver disease? What does Disseminated Intravascular Coagulation (DIC) with? What may contribute to ineffective intravascular coagulation? What are enzymes released from diseased liver tissue? What are the cytosolic enzymes? What are Mitochondrial and cytosolic isoenzymes in hepatocytes? What are the canalicular membranes of hepatocytes? AST activity is what times that of ALT? Are hepatocyte activities of LD higher or lower than that of AST and ALT relative to plasma? Are plasma activities of LD higher or lower than those of ALT and AST? What is the simplest mechanism of enzyme release from diseased liver tissue? What enzyme does alcohol appear to induce to expression of on the surface of hapatocytes? The release of what two enzymes appears to be associated with increased synthesis, membrane fragmentation by bile acids, and solubilization of membrane-bound enzymes of bile acids? What is the half-life of ALT? What is the half-life of AST? What does the much longer half-life of ALT lead to? Pre-sinusoidal, sinusoidal, and post sinusoidal. Pre-sinusoidal Post sinusoidal Factor I (Fibrinogen) Factor II (Prothrombin) Factor V (Proaccelerin) Factor VII (Proconvertin) Factor X (Stuart Factor) Vitamin K deficiency Prolonged PTT Hepatic necrosis Thrombocytopenia Aspartate aminotransferase (AST, SGOT) Alanine aminotransferase (ALT, SGPT) Alkaline phosphatase (ALP) γ- glutamyltransferase (GGT) Lactate dehydrogenase (LDH) AST, ALT, and LD AST, ALT ALP and GGT Two times Lower Higher Cell injury Mitochondrial AST GGT and ALP 48 hours 16-18 hours Higher activites of ALT than AST in most forms of hepatocellular injury 30 Chem PPT Flashcards, Unit 4 What is the half-life of liver isoenzyme of ALP? 1 to 10 days What is the reported half-life of GGT? 4.1 days What are disorders of bilirubin metabolism? Unconjugated hyperbilirubinemia, and conjugated hyperbilirubinemia What is increased in unconjugated Production of unconjugated bilirubin from hyperbilirubinemia? heme What is decreased in unconjugated decreased delivery of unconjugated bilirubin hyperbilirubinemia? in plasma to hepatocyte decrease uptake of unconjugated bilirubin across hepatocyte membrane decreased storage of unconjugated bilirubin decreased conjugation What is decreased in conjugated decrease secretion of conjugated bilirubin into hyperbilirubinemia? canaliculi decreased drainage What is conjugated hyperbilirubinemia also Cholestasis known as? What five viruses have been identified in A, B, C, D, and E. hepatic viral infection? What is the most common cause of acute viral Hepatitis A (HAV) hepatitis? What is Hepatitis A associated with? Waterborne and foodborne contamination Does Hepatitis A have a chronic form? No How is Hepatitis B virus transmitted? Parenteral, sexual, or from mother to child after delivery (vertical transmission). How is Hepatitis B prevented ? It can be prevented by passive (hepatitis B immune globulin [HBIG]) or active (hepatitis B recombinant vaccine) immunization What is the most common cause of chronic Hepatitis C virus hepatitis? What is the major risk factor for acquiring Hepatitis C major risk factor include injection Hepatitis C virus? from drug use as well as transfusion before testing the blood supply What is used to detect the presence of Hepatitis HCV RNA is used to detect the presence of C virus? Hepatitis C virus. The known causes of transmission of Hepatitis Fecal-Oral and Household. D, and E viruses are? What is acute hepatitis? Acute injury directed against hepatocytes which may either be directly or indirectly. Give an example of a drug that causes direct Acetaminophen injury to hepatocytes. What is indirect injury to hepatocytes? Indirect injury is immunologically mediated injury that occurs with hepatitis viruses and most drugs including ethanol. A person with Wilson’s Disease will show an 3-10 URL increase of ALT/AST Upper reference limit by 31 Chem PPT Flashcards, Unit 4 how much? What is the Bilirubin level for someone with viral, alcoholic, drug induced, autoimmune hepatitis, and Wilson’s Disease? What is acute alcoholic hepatitis characteristically associated with? What drug has a toxic metabolite that can cause Toxic hepatitis? What is another term for Ischemic Hepatitis? What is increased during Ischemic Hepatitis? What is Cholestatic Hepatitis? What is chronic hepatitis? What are the two major components of chronic hepatitis? What is ALT activity strongly correlated with and NOT strongly correlated with? What are the most common causes of Chronic hepatitis? How is idiopathic hepatitis diagnosed? α1- Antitrypsin deficiency is diagnosed by? How many genotypes of Chronic Hepatitis C are there? What is the test performed after 24 weeks after completion of treatment for Hepatitis C? How are the results after completion of treatment for Hepatitis C interpreted? What are the diseases associated with fat and inflammation of the liver not associated with alcoholism? NAFLD and NASH are associated with what diseases? What is Autoimmune Hepatitis? What are the most important antibodies for the diagnosis of Autoimmune Hepatitis? 5-10 mg/dL Leukocytosis and increased concentrations of acute phase response proteins. Acetaminophen Hypoperfusion Cytosolic enzymes It is the obstruction of bile secretion and dysfunction of bile canaliculi in the Golgi apparatus of the liver cells. It’s the continuous inflammatory damage to hepatocytes lasting more than six months, accompanied by hepatocytes lead generation and scarring. Fibrosis and necroinflammatory activity. ALT activities are strongly correlated with necroinflammatory activity, but not with fibrosis. Chronic HBV, chronic HCV, and nonalcoholic steatohepatitis (NASH). Through liver biopsy and the absence of markers. α1- AT Phenotype. 24 Sensitive HCV RNA. Results can be treated as nonresponder, treatment responder, relapser, and sustained virologic response (SRV) Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) Autoimmune Hepatitis is a rapidly progressing form of chronic hepatitis associated with the presence of autoimmune markers and substantial hypergammaglobulinemia. Antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver32 Chem PPT Flashcards, Unit 4 What is the Antigen target for Anti-LKM1 What are the Antigen targets for ASMA What are the most common drugs involved with drug induced chronic hepatitis? What have been linked to chronic hepatitis? What is Liver Disease? What is genetic Liver Diseases that presenting as Chronic Hepatitis? What is Hemochromatosis? What is Alpha I-antirypsin? What is Wilson disease? What is Alcoholic Liver Disease? What is Cirrhosis? What is Cholestatic Liver Disease What is Primary biliary Cirrhosis (PBC)? What is primary sclerosing Cholangitis (PSC)? kidney microsomal antigen type I (LKM1) Cytochrome P450 IID6 Actin, Tubulin, Vimentin, Desmin, Skelitin Nitrofurantoin, Methyldopa, and HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors. Herbal Medications When the liver or hepatocyte function abnormality cause inflammation, fibrosis, scarring. 1. Hemochromatosis 2. Alpha I – Antitrypsin (AAT) deficiency Wilson Disease A rare genetic disorder, due to abnormalities in genes that regulates iron metabolism. Is a major protein serine protease inhibitor (serpin) in plasma, and is decreased homozygous deficiency and cirrhosis and increased by acute inflammation. An autosomal recessive disorder associated with excessive quantities of copper in the tissue particularly the liver and central nervous system. Risk factors for developing alcoholic liver disease include duration and magnitude of alcohol abuse, sex, presence of co-infection with HBV or HCV, and nutritional state. Defined anatomically as diffuse fibrosis with nodular regeneration, represents the end-stage of scar formation and regeneration in chronic liver injury. Stoppage or suppression of the flow of bile is associated with the retention of bile within the excretory system, which may be due to gallstones in the bile ducts (choledocholelithiasis), narrowing (strictures) and tumors. Also known as nonsuppurative destructive cholangitis, is an uncommon autoimmune disorder targeting intrahepatic bile ducts primarily in middle age women (6:1 female to male ratio). A chronic inflammatory disease of the biliary tree, most commonly affecting extrahepatic bile ducts, characterized by the presence of 33 Chem PPT Flashcards, Unit 4 What is Gallstones? What is Hepatic Tumors? What is Hepatocellular Carcinoma (HCC)? What are the preferred Tests of Hepatic Function: Bilirubin Test ALP test AST Test ALT Test Albumin Test PT Test What is the Specimen of choice for liver disease? What is serum albumin? What is the purposed of Prothrombin time test (PT)? anti-neutrophil cytoplasmic antibodies (ANCA) Are solid formations in the gallbladder that are composed of cholesterol and bile salts. the most important primary liver tumor is hepatocellular carcinoma (HCC). the major risk factor for development of HCC is infection with HBV or HCV. the most widely used tumor marker is AFP. A cancer arising from hepatocytes, complication of HBV and HCV also cause HCC. Diagnosing jaundice, modest correlation with severity. Alkaline phosphatase diagnosing cholestasis and space-occupying lesions Aspartate Aminotransferase Sensitive test of hepatocellular Disease; AST > ALT in alcoholic disease, cirrhosis Alanine aminotransferase sensitive and more specifc of hepatocellular disease. Indicator of chronicity and severity Prothrombin test indicator of severity, early indicator of cirrhosis in chronic hepatitis Serum albumin Useful in assessing the chronicity and severity of liver disease. Serum albumin concentration is decreased in chronic liver disease. Also decreased in severe acute liver disease, in inflammatory disorders, malnutrition, and with nephrotic syndrome. serial measurements of serum albumin also are used to assess the severity of liver disease serial PT measurements are used to determine in synthetic liver function. more reliable done albumin measurements because fewer 34 Chem PPT Flashcards, Unit 4 What are the major organs of the G.I. Tract include: What are 3 major zones off the Stomach? What is cardiac Zone Secret? What is the body of stomach secret? What is the Pyloric Zone Secret? What is the function of the small intestine (SI)? What are the 3 parts of the SI? What is the Function of Duodenum? What is the function of Jejunum? What is the function of ileum? What is the function of large intestine? What are the 5 parts of Large Intestine? conditions (other than warfarin administration) affect PT then affect albumin. PT is the most important prognostic marker in acute liver disease and is usually the first function tests to become abnormal as chronic hepatitis evolves into cirrhosis. • Stomach • Small intestines • Large intestines • Pancreas Gallbladder Three major zones: cardiac zone, body pyloric zone Secretion of Mucus Secretion of HCL, enzymes, mucus, and intrinsic factor. Secretion of mucus, pepsinogen, and gastrin Converts food into chime and Duodenum Jejunum Ileum Is the 1st and shortest segment of the small intestine. It receives partially digested food (known as chime) form the stomach and plays a vital role in the chemical digestion of chime in preparation for absorption in the small intestine. Is specialized for the absorption, by the enterocytes, of small nutrient particles which have been previously digested by enzyme in the duodenum. Mainly to absorption of B12 and bile salt and whatever products of digestion were not absorbed by the jejunum. Is to absorb water from the remaining indigestible food matter and transmit the useless waste material from the body. Cecum Appendix Colon Rectum anal canal 35 Chem PPT Flashcards, Unit 4 Cecum Appendix Colon What is Function of Pancreas? What is the function of Gallbladder? What is bile? What is Zollinger-Ellison (Z-E) syndrome? Where was the Zollinger-Ellison (Z-E) tumor found? What are the characteristics of Zollinger-Ellison (Z-E) syndrome? What were the evidences caused increased the concentration of high serum gastrin? What is the definition of Gastritis? Where were leading to Erosive gastritis (Acute gastritis)? What was the technique used to diagnosis for Erosive gastritis (Acute gastritis)? How is Nonerosive gastritis (Chronic gastritis) associated with peptic ulcer? Store food material where bacteria are able to break down the cellular. Acts as a storehouse for good bacteria, rebooting the digestive system after diarrheal illness. Is to reabsorp fluids and precess waste products from the body and prepare for its elimination. Are secreted into small intestine to further break down food after it has left the stomach. The gland also produces the hormone insulin and secretes it into the bloodstream in order to regulate body glucose or sugar level. Is to store and concentrate bile, a yellowbrown digestive enzyme produce by the liver. Is a digestive juice that secreted by the liver and stored in gallbladder. Important functions: 1. assists with fat digestion and absorption in the gut 2. body to excrete waste product from blood. Increase absorption of fats, it’s an important part of absorption of fat-soluble substances, such as Vitamins A, D, E, K. Results from a tumor (gastrinoma) of the pancreatic islet cells The primary tumors classically occur in the pancreas, duodenum or intestinal lymph nodes, but also occur in other organs it is characterized by fulminant peptic ulcers, massive gastric hypersecretion, hypergastrinemia, diarrhea and steatorrhea. The documentation of an increased basal acid output (BAO) in gastric juice provide strong evidence that the high serum gastrin concentration is caused by Z-E syndrome. Is the term used to denote mucosal inflammation of the stomach Occurs in individual after severe trauma, or severe burns (Curling ulcer) and craniotomy or traumatic head injuries Diagnosed by endoscopy Associated with peptic ulcer disease or gastric carcinoma, the period after partial 36 Chem PPT Flashcards, Unit 4 What are other names of Celiac disease? Where would Celiac disease, a lifelong autoimmune intestinal disorder, is found in? What is the external trigger to Celiac disease’s development? What antibodies used to diagnose celiac disease? What can be used as measurement to diagnosed Celiac disease? For a definitive diagnosis, what is a jejunum biopsy required? What does Disaccharidase deficiency lead to? gastrectomy, pernicious anemia, H. pylori infection and healthy elderly individuals - non-tropical sprue - Celiac Sprue Gluten-Sensitive Enteropathy individuals who are genetically susceptible found in gluten, which is a complex group of proteins present in wheat Immunoglobulin A (IgA) antibodies tissue transglutaminase (tTG) antibodies for endomesial antibodies (EMA) - antireticulin antibodies (ARA) Antigliadin antibodies with the characteristic changes in villous atrophy, increased intraepithelial lymphocytes, and hyperplasia of the crypts - Lactose intolerance - Congenital lactase deficiency - Acquired lactase deficiency - Sucrase-Isomaltase and Trehalase deficiencies - What are the methods to detect lactase deficiency? What are diseases lead to from a bacterial overgrowth? - Lactase in mucosal biopsy Oral lactose tolerance - bile salt deficiency, which causes fat malabsorption Vitamin B12 deficiency What does diagnostic gold standard require? intubation with aspiration of jejunal contents and the demonstration of a bacterial count of >107 organisms/mL and >104 anaerobes/mL - Jejunal diverticuli - Crohn disease - Automatic neuropathy - Scleroderma - Pseudo obstruction Postgastretomy Following cholecystectomy and in some patients with irritable bowel syndrome (IBS) - selenohomocholyltaurine test - Measurement of serum 7a-hydroxy-4cholesten-3-one levels Therapeutic trial of bile acids sequestrants What are the small intestine abnormalities associated with bacterial growth? When does Bile salt malabsorption occur? Procedure for the diagnosis of bile salt malabsorption 37 Chem PPT Flashcards, Unit 4 What are Inflammatory bowel disease (IBD) What can IBD be diagnosed by? What is the diagnose of Protein-losing enteropathy? How does Protein-losing enteropathy diagnosed? What is Cystic fibrosis (CF) What is a reliable test for pancreatic insufficiency in infants over the age of 2 weeks with CF, and in older children at diagnosis of the disorder? What are the Adult disorders of exocrine pancreas What are Invasive test of pancreatic exocrine function? What are noninvasive test of pancreatic exocrine function? What might lead to Carcinoid tumors? What are the clinical presentations of maldigestion/malabsorption? What are the causes of chronic diarrhea? What are the main functions of bone? What’s the composition of bones and function of each? What are the two main types of bone cells? such as cholestyramine Crohn disease, ulcerative colitis and a number of microscopic inflammatory bowel disorders diagnosed by fecal lactoferrin or calprotectin determinations patients with hypoalbuminemia in whom renal loss, liver disease and malnutrition have been excluded measuring the fecal clearance of alpha-1 antitrypsin as a marker of G.I. protein loss the most common severe autosomal recessive disease affecting the pancreas measurement of pancreatic elastase-1 in feces - Acute pancreatitis - Chronic pancreatitis Carcinoma of the pancreas - Lundh test - Secretin stimulating test Secretin CCK test - Fecal chymotrypsin - Fecal elastase 1 - NBT-PABA - Pancreolauryl 13C mixed chain tryglyceride absorption - Pancreatic tumors - Insulinomas - Gastrinomas - VIPomas (Werner-Morrison syndrome) - Detection of chromogranin A - Somatostatinomas Glucagonomas Evidence of general ill health, isolated nutritional deficiencies, abdominal symptoms, watery diarrhea and possibly steatorrhea. Carbohydrate malabsorption, laxative use, VIPoma, ulcerative colitis, crohn’s disease. Mechanical, protective and metabolic. Cortical bone (80% of mineral) to primarily mechanical and protective, trabecular bone (20% of mineral) function is more metabolically active. Osteoclasts and osteoblasts. 38 Chem PPT Flashcards, Unit 4 What is the function of osteoclasts? What is the function of osteoblasts? What are the remodeling or turnover of bone cycles? How do osteoblasts form bone? What is bone growth and turnover influenced by? What are the percentages of bone content and the specific mineral? What does the concentration of these electrolytes in plasma depend on? What principal hormones regulate these processes? What is the 5th most common element in the body? What is the body’s content of calcium? What states does calcium exist in the blood? What is the calcium regulating hormone? What are the physiological functions of intracellular calcium? What is extracellular calcium needed for? What does a decrease in serum free calcium concentration cause? What does an increase in serum free calcium concentration cause? What is the clinical significance of calcium? What Spectrophotometric methods can you use to measure total calcium? Osteoclasts resorb bone, which is the process that osteoclasts break down bone and release minerals, resulting in a transfer of calcium from bone fluid to blood. Osteoblasts function is to synthesize new bone. It’s a cell that secretes the matrix for bone formation; a cell that makes bone. Activation, resorption, reversal, formation, rest phase. By synthesizing the organic matrix, including type I collagen and participating in the mineralization of newly synthesized matrix. Metabolism of calcium, phosphate, magnesium and by many hormones specially parathyroid hormone (PTH)< 1,25dihydroxyvitamin D (1,25 [OH]2D) and several cytokines. Bone contains nearly all the calcium (99%), most of the phosphate (85%), and much of the magnesium (55%) of the body. The net effect of bone mineral deposition and resorption, intestinal absorption and renal excretion. PTH and 1,25(OH)2D. Calcium, and is the most prevalent cation. 99% predominantly as extracellular crystals of hydroxyapatite, Ca10(PO4)6(OH)2. Ionized (50%), bound to plasma proteins, primarily albumin (40%), complex with small ions (10%). PTH and 1,25(OH)2D. Muscle contraction, hormone secretion, glycogen metabolism and cell division. Bone mineralization, blood coagulation, and other functions. Neuromuscular excitability and tetany. It reduces neuromuscular excitability. Hypocalcemia and hypercalcemia. 1) o-Cresolpthalein Complexone method 2) Arseno III method 3) Ion-Selective Electrode methods 4) Atomic Absorption Methods 39 Chem PPT Flashcards, Unit 4 What are the Specimen requirements for the total calcium measurements? 1) Serum and heparinized plasma are the preferred specimens for total calcium determination. 2) Citrate, oxalate,and EDTA anticoagulants should not be used because they interfere by forming complexes with calcium. 3) Co-precipitation of calcium with fibrin in heparinized plasma or lipids has been reported with storage or freezing. 4) Urine specimens a should be preserved by adding 20 to 30 mL of 6 mol/L HCl per 24 hours specimen (1 to 2 mL for a random specimen) to prevent calcium salt precipitation. What area some interferences for the total measurement of calcium? What can you use to measure free (ionized) Calcium? What are some interferences with the measurements of Free (Ionized) Calcium? what are the specimen requirements of free (ionized) Calcium? 1) Hemolysis, icterus, lipemia, paraproteins, magnesium and gadolinium chelates in contrast agents interfere with photometric methods. 2) Remedy: use of bichromatic analysis, multi-wavelength corrections, or blanking to reduce interference Ion- Specific Electrode methods Ionic strength of the specimen anionic surfactants and ethanol effect of pH 1) Specimens must be collected and handled anaerobically and promptly to minimize alterations in pH and free calcium due to the loss of CO2 and the metabolism of blood cells. 2) Syringes and evacuated tubes should be filled completely and sealed to prevent the loss of CO2 (increase in pH). 3) Specimens should be handled to prevent the production of lactic acid (decrease in pH) by erythrocytes or white blood cells during anaerobic metabolism or glycolysis. 40 Chem PPT Flashcards, Unit 4 4) Specimen should be collected, transported and maintained on ice to prevent anaerobic metabolism. 5) Free calcium is measured in heparinized whole blood, heparinized plasma or serum. 6) Free calcium is stable in whole blood specimens for 1 hour at room temperature and for 4 hours at 4°C. What are the effects of anticoagulants on Free (Ionized) Calcium? What are the patient Preparation and Sources of Preanalytical Error for Total and Free Calcium Measurements? 7) The free calcium concentration and the actual pH of the specimen should be reported on each specimen. The pH is useful in verifying that the specimen has been properly handled. 1) Heparin is the only acceptable anticoagulant for free calcium determinations 2) Liquid heparin should be avoided since it may falsely low free calcium levels. 3) Citrate, oxalate, and EDTA bind calcium and unacceptably decrease free calcium concentration 1) Use of tourniquet (if required), should be applied just before sampling and released within 1 minute. 2) Fist clenching or other forearm exercise should be avoided before phlebotomy to prevent decrease in pH (due to lactic acid production) and an increase in free calcium. 3) Avoid sudden changes in posture. 4) Inactivity such as bed rest can lead to bone resorption and increase total and free calcium in blood. 5) Hyperventilation decreases concentration of free calcium. 6) Exercise increases the concentration of free calcium. 7) Both serum free calcium and calcium excretion are lower during the night 41 Chem PPT Flashcards, Unit 4 What is Phosphate? Inorganic phosphate is the fraction measured in? In blood, organic phosphate esters are located primarily within? Inorganic phosphate is a major component of? How is phosphate measured? What is are the preferred specimens? Citrate, oxalate and EDTA should not be used because? Is concentration of inorganic phosphate about 0.2 to 0.3 mg/dL or 0.06 to 0.10 mmol/L lower or higher in heparinized plasma than in serun? True or false phosphate concentrations in plasma or serum are decrease by prolonged storage with cells at room temperature ? What is the name for specimens that are unacceptable because erythrocytes contain high concentrations of organic phosphate esters, which hydrolyze to inorganic phosphate ? What molecule is increases in hemolyzed specimens stored at 4*C more rapidly at room temperature 37*C Phosphate is ____1_ in separated serum for days at 4*C and for ___2___ when frozen provided evaporation is prevented What molecule is the fourth most abundant cation in the body ? 55%of the total body _______is in the skeleton and 45% is intracellular Within the cell most of the magnesium is bound to ______ and ________________notably ATP What molecule is a cofactor for more than 300 enzymes required for enzyme substrate complex formation and an allosteric activator of many enzyme systems Which molecule is metabolized in a cell to produce energy for performing work? True or false ? the potential energy in an ATP Phosphorus in the form of inorganic and organic phosphate is an important and widely distributed element in the human body. Plasma and serum by clinical laboratories. Cells and incorporated into nucleic acids, phospholipids, phosphoproteins, and highenergy compounds, such as ATP. Hydroxyapatite in bone. Based on the reaction of phosphate ions with ammonium molybdate to form a phosphomolybdate complex that is measured spectrophotometrically. Serum and heparinized plasma They interfere with the formation of the phosphomolybdate complex. Lower in heparinized plasma than in serum False Hemolyzed Inorganic phosphate 1. stable months Magnesium Magnesium 1. proteins negatively charged molecules Magnesium Glucose True 42 Chem PPT Flashcards, Unit 4 molecule is derived mainly from its three phosphate groups Which process is not part of the cellular respiration pathway that produces large amounts of ATP in a cell? Inonezed calcium is characterized as ? Which is the physiological active form of calcium ? Phosphomolybdate is used to measure which of the following ? TSH is secreted by the ? Which of the pituitary hormones regulates renal free water excreation to maintain homeostasis Serum thyroid-stimulating hormone levels are decreased in ? Tetraiodothyronine describes which thyroid hormone? The principle method used to measure hormone levels in blood in most clinical labs is ? Free thyroxine assays measure ? What would be the predicted results for the following lab tests for a patient with hypothyroidism ? Crushing syndrome is characterized by? What are some of the parathyroid hormone hyposecreation symtoms ? What are some of the Parathyroid hormone fuctions are ? Where is the parathyroid horomone located ? What are the thyroid glands composed of ? True or false? PTH acts directly on bone and kidney What technique is used for the measurement of parathyroid hormone? Specimen used for the measurement of parathyroid hormone Sources of Vitamin D. Fermentation Free or unbound Ionized Inorganic phosphorus Anterior pituitary Antidiuretic hormone Primary hyperthyroidism T4 (thyroxine) Immunoassays Only the unbound thyroxine level Elevated TT4 below normal FT4 elevated TSH Excess secretion of pituitary ACTH 1.Low blood calcium (hypocalcemia 2. Nerve discharge and seizutes 3. Muscle sparms Raises blood calcium Stimulates release of calciumfrom bones Indirectly increases activity of and number of osteoclast Stimulates final conversion of vitamin Din the kidneys Calcidiol into calcitriol, calcitriol aids calcium absorption in the small intestine Bilaterally in the neck two on the left and two on the right Chief and oxyphil cells that synthesize ,store and secrete PTH True Two-site or sandwich immunoassays Serum or EDTA plasma It is produced endogenously by exposure of skin to sunlight and absorbed from foods 43 Chem PPT Flashcards, Unit 4 Main circulating form of Vitamin D. Biologically active form of Vitamin D. Metabolites of vitamin D. What is the rle of 1,25(OH)2D in small intestine? primarily fish liver oils, fatty fish, egg yolks and liver. 25-hydroxyvitamin D [25(OH)D] 1,25-dihydroxyvitamin D [1,25(OH)2D] -Cholecalciferols (Vitamin D3) -Ergocalciferols (Vitamin D2) It stimulates calcium absorption, primarily in the duodenum, and phosphate absorption in the jejunum and ileum. Effects of 1,25(OH)2D on BALP and OC? By stimulating osteoblast, 1,25(OH)2D also increases the circulating concentration of bone alkaline phosphatase (BALP) and the non-collagenous bone protein osteocalcin (OC). Role of 1,25(OH)2D in kidneys. In the kidneys, 1,25(OH)2D inhibits its own synthesis and stimulates its metabolism. Clinical significance of Vitamin D and its Useful in evaluating hypocalcemia, vitamin D metabolites. status, bone disease and other disorders of mineral metabolism. Useful in detecting inadequate or excessive hormone production in the evaluation of hypercalcemia, hypercalciuria, hypocalcemia and bone and mineral disorders. Measurement techniques of Vitamin D -Competitive Protein Binding Assay (CPBA) metabolites -Immunoassay -UV absorbance after separation by -High Performance Liquid Chromatography (HPLC) -Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) What is Calcitonin? It is a 32-amino acid linear polypeptide hormone that is produced in humans primarily by the parafollicular cells (also known as Ccells) of the thyroid. What is Parathyroid hormone-related protein (or It is a protein member of the parathyroid PTHrP) ? hormone family. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell lung carcinoma). However, it also has normal functions. Role of PTHrP. It acts as an endocrine, autocrine, paracrine, and intracrine hormone. What happened If PTHrP stimulate? PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and 44 Chem PPT Flashcards, Unit 4 inhibition of proximal tubular phosphate transport. By Which method PTHrP can be measured? By Which way PTHrP can be protected? What is Osteoporosis? What is cause by Osteomalacia and Rickets? Osteomalacia or rickets done by which deficiency? What is the types of Disorders of Bone and mineral in chronic kidney disease (Renal Osteodystrophy)? Define Paget Disease of Bone. Pituitary Gland also called what? Pituitary gland located in a bone cavity, known as _____, found at the base of the __________ The anterior lobe of the pituitary gland is known as? The posterior lobe of the pituitary gland is known as? Anterior Pituitary Cells is responsible for Anterior Pituitary Cells synthesize both _____ and ______ hormones in response to signals from the hypothalamus Trophic hormones stimulate its target organ to PTHrP can be measured by competitive and noncompetitive immunoassays A combined mixture of aprotinin, leupeptin, pepstatin, and EDTA provides the greatest protection. Osteoporosis is a disease of bones where bone mineral density is reduced and the amount and variety of proteins in bone is altered. Osteomalacia and Rickets Caused by a mineralization defect during bone formation, resulting in an increase in osteoid, the unmineralized organic matrix of bone. Osteomalacia or rickets is usually due to either vitamin D deficiency or phosphate depletion. -High-turnover bone disease Osteitis fibrosa or secondary hyperparathyroidism -Low-turnover bone diseases osteomalacia adynamic (aplastic) bone disease Paget Disease of Bone is a localized disease of bone characterized by osteoclastic bone resorption, followed by replacement of bone in a chaotic fashion. a disease that affects the skull, femur, pelvis and vertebra. the most common finding leading to the diagnosis of Paget disease is increased serum activity of ALP. hypophysis 1. sella turcica skull Adenohypophysis) / Anterior pituitary Neurohypophysis) /Posterior pituitary hormone production. 1. trophic non- trophic target hormones (TSH) 45 Chem PPT Flashcards, Unit 4 release what? Non-trophic hormones acts directly without the production of a what? What are the Anterior Pituitary Gland hormones? What are 3 glycoprotein hormones that process a common alpha subunit and a distinct beta subunit that confers biologic specificity. ACTH, PRL, and GH what type of hormones? What cells do not synthesize any known hormone but serve as a storage area for hormones produced by the hypothalamus 2 hormones that are stored in the posterior pituitary gland are Disorders of the pituitary gland either pituitary adenoma or pituitary hyperplasia are Primary or Secondary factors? disorders of the hypothalamus or ectopic origin are primary or secondary factors? Hyposecretion can be decreased secretion of one hormone, a group of hormones, or all hormones (panhypopituitarism). This is what type of disorder? What causes hypersecretion of one hormone which commonly results in hyposecretion of remaining pituitary hormones (due to destruction of pituitary gland by the growing tumor) What is a protein hormone synthesized and released from the anterior pituitary is response to stimulation from the hypothalamic growth hormone releasing factor (GHRH). This is also know as? What is Growth hormone stimulated by? How does growth hormone affect metabolic processes? During daytime hours, plasma concentration target hormone (PRL) Melanocyte Stimulating Hormone Prolactin (PRL) Growth Hormone (GH); Somatotropin Luteinizing Hormone (LH) Follicle-Stimulating Hormone (FSH) Thyroid-Stimulating Hormone (TSH) Adrenocorticotrophic Hormone (ACTH) TSH, LH and FSH polypeptide Posterior Pituitary 1.Oxytocin 2. Anti-diuretic Hormone (ADH); Vasopressin Primary Secondary Anterior Pituitary Disorder Pituitary adenoma Growth Hormone exercise, physical and emotional stress, hypoglycemia, increased amino acid levels (arginine), hormones (testosterone, estrogen, thyroxine) by stimulating protein synthesis and fat and glucose metabolism Growth Hormone 46 Chem PPT Flashcards, Unit 4 remains stable and relatively low. Secretory spikes occur approximately 3 hours after meals and after exercise. Marked rise approximately 90 minutes after the onset of sleep; concentrations reached a peak value during the period of deepest sleep. Depressed by abnormally high levels of glucocorticoids. This is all done by what type of hormone? IGF is a family of small peptides formed in the liver under the control of GH that exhibit similar activity as _______. Where do IGF's circulate? Active in stimulating many aspects of cell growth particularly that of what type of tissue? The most important of the IGFs is IGF-I. In addition to its growth promoting effects on cartilage and insulin -like activity in other tissues, it increases _______ in adipose tissue and stimulates glucose and amino acid transport into muscle and heart muscle. Synthesis of what two substances is enhanced by IGF-I, which also has positive effects on calcium, magnesium and potassium homeostasis. What are 2 examples of Hypersecretion of Growth Hormone? What is Acromegaly in adults? What is pituitary gigantism in children? What is an example of Hyposecretion of Growth Hormone? What is Pituitary Dwarfism? insulin in blood, complexed to specific plasma binding proteins (Insulin-like growth factor binding protein [IGFBP]-3) cartilage glucose oxidation 1. collagen proteoglycans Acromegaly in adults Pituitary gigantism in children An extremely rare syndrome that results when the anterior pituitary gland produces excess growth hormone (GH) after epiphyseal plate closure at puberty. It results from pituitary adenoma secreting GH and compression of adjacent tissues of the pituitary gland, causing hyposecretion of other trophic hormones. Pituitary dwarfism Growth hormone deficiency A condition in which the pituitary gland does not make enough growth hormone. This results in a child's slow growth pattern and an unusually small stature but proportionally built. 47 Chem PPT Flashcards, Unit 4 Name 3 Analytical Methods used for Growth Hormone testing. What does PRL stand for? Give at least 3 aliases for PRL. What is PRL is a hormone secreted by? What is under inhibitory control by the hypothalamic dopamine? What occurs during Hypersecretion (Hyperprolactenemia) of PRL? What occurs during Hyposecretion (Hypoprolactenemia) of PRL? What is the main analytical method used for the testing of Prolactin (be specific)? What occurs during a Two-site immunometric (“sandwich”) assay? What does ACTH stand for? What is ACTH? Where is ACTH secreted from? What are some aliases for ACTH? What does ACTH act primarily on? What does ACTH do to the Adrenal Cortex? When does ACTH production is increased? Give an example of Hypersecretion of ACTH. What is Cushing’s Syndrome? Immunoassays Mass spectrometry methods Stimulation tests - Insulin tolerance tests Prolactin - Lactogen - Lactotropin - luteotropin - mammotropin - galactopoietic - lactation - lactogenic luteotropic hormone Specialized cells within the adenohypophysis termed lactotrophs A polypeptide Prolactinomas Galactorrhea Infertility & amenorrhea in women Oligospermia or Impotence in men Lack of lactation in postpartum women Immunoassays: Two-site immunometric (“sandwich”) assay The signal antibody is labeled with a detection molecule such as an enzyme, fluorophore, or chemiluminescent tag. Adrenocorticotrophic Hormone A peptide hormone secreted by the adenohypophysis is one of the derivatives of pro-opiomelanocortin (POMC Adenohypophysis Corticotropin Corticotrophin Adenocorticotrophin Adenocorticotropin Adrenal cortex Stimulating its growth and the synthesis and secretion of corticosteroids, most importantly, cortisol. During times of stress Cushing’s Syndrome A disease is caused by a tumor (pituitary adenoma) or excess growth (hyperplasia) of the pituitary gland. or excess production of a 48 Chem PPT Flashcards, Unit 4 What is Cushing’s Syndrome characterized by? What are useful tests for the diagnosis of Cushing syndrome/disease? What is Hyposecretion of ACTH? What are 3 signs of Hyposecretion of ACTH What are some of the tests used for the diagnosis of secondary adrenal insufficiency due to CRH-ACTH deficiency? Describe Thyroid Stimulating Hormone (TSH) What are some of the steps involved in thyroid hormone synthesis? What is a Follicle stimulating hormone (FSH)? What is a Luteinizing hormone (LH)? non-endocrine tumor truncal obesity hyperglycemia hypertension protein wasting 1. 24 hour excretion of urinary-free cortisol 2. Dexamethasone suppression tests (both overnight with 1 mg and 48 hours with 2 mg per day) 3. Demonstration of loss of the diurnal variation with inappropriately increased cortisol concentrations in the evening as assayed by plasma or salivary cortisol. ACTH deficiency or secondary hypoadrenalism weight loss weakness gastrointestinal problems Cosyntropin test, Overnight metyrapone test, Insulin tolerance test, Cosyntropin infusion tests over several days. Thyroid Stimulating Hormone (TSH) is a glycoprotein peptide hormone synthesized by the thyrotroph cells of the adenohypophysis that promotes the growth and uptake of iodine by the thyroid gland and stimulates the synthesis and secretion of thyroid hormones from the thyroid gland. It is also called thyrotropin. Uptake of iodine, organification of iodine onto tyrosine, coupling of tyrosines, proteolytic release of stored thyroid hormone from thyroglobulin stores. A Gonadotropins that is synthesize in the adenohypophysis and stimulates the growth and maturation of ovarian follicles, stimulates estrogen secretion, promotes the endometrial changes characteristic of the first phase (proliferative phase) of the menstrual cycle, and stimulates spermatogenesis in the male. It is also called follitropin. A Gonadotropin that synthesize in the adenohypophysis and acts with FSH to promote ovulation and secretion of androgens and progesterone. 49 Chem PPT Flashcards, Unit 4 It initiates and maintains the second (secretory) phase of the menstrual cycle. In females, it is concerned with corpus luteum formation. In males, it stimulates the development and functional activity of testicular Leydig cells and testosterone production. LH is also called interstitial cell stimulating hormone and lutropin What is the difference between Hypersecretion Hypersecretion results in sexual precocity and Hyposecretion? which is usually a result of brain tumors in the region of the hypothalamus while Hyposecretion results in sexual underdevelopment and infertility What is Anti-diuretic hormone (ADH)? Anti-diuretic hormone (ADH) is an hormones of the Neurohypophysis also known as arginine vasopressin and vasopressin.Formed by neuronal cells of hypothalamic nuclei and stored in the neurohypophysis. Osmolality of the blood is the main regulator of ADH secretion. The major physiological function is the control of water homeostasis, which allows the kidney to reabsorb water and concentrate urine. What are the functions of ADH? •to stimulate contraction of the muscles of capillaries and arterioles, increasing blood pressure •promote contraction of the intestinal musculature, increasing peristalsis •exert contractile influence on the uterus •have a specific effect on the epithelial cells of renal collecting tubules How is the concentration of plasma ADH? Plasma ADH concentrations are “inappropriately” increased relative to a low plasma osmolality and to a healthy or increased plasma volume What are some of the symptoms in patients with The typical patient with SIADH has: hyponatremia ,hypoosmolar plasma (< 280 Syndrome of Inappropriate ADH secretion mOsm/kg) ,urine osmolality >100 mOsm/kg , (SIADH)? urine sodium concentration that is inappropriately elevated (> 40 mmol/L). What causes Diabetes insipidus? Diabetes insipidus results from destruction of the posterior pituitary gland or the hypothalamus causing insatiable thirst, 50 Chem PPT Flashcards, Unit 4 The three main categories of diabetes insipidus are? What causes HDI, NDI, and Polydipsia? Where is oxytocin synthesized? What are the primary functions of oxytocin? What is the primary stimulus for release of oxytocin? What reaction would occur with stimulation of stretch receptors in the uterus and in the vaginal mucosa? What is the purpose of oxytocin in a Male? What gland lies at the upper pole of each kidney, pyramidal in shape, and weighs approximately 4 grams regardless of age, weight, or sex? Name the 2 sections to an adrenal gland? What are the 3 layers that make up the adrenal cortex? Which layer of the adrenal cortex is the outermost zone and constitutes approximately 15% of the cortex? Name the middle layer that composes about 75% of the cortex with large and lipid laden cells? polydipsia, and polyuria. Hypothalamic diabetes insipidus (HDI) , Nephrogenic diabetes insipidus (NDI), and Psychogenic or primary polydipsia. . Hypothalamic diabetes insipidus (HDI) also called neurogenic, central or cranial diabetes insipidus, It is caused by a failure of the pituitary gland to secrete normal amounts of ADH in response to osmoregulatory factors Nephrogenic diabetes insipidus (NDI) results from the failure of the kidney to respond to typical or increased concentrations of ADH. Psychogenic or primary polydipsia a chronic, excessive intake of water suppresses ADH secretion and produces hypotonic polyuria In the hypothalamus as part of a preprohormone, along with a separate neurophysin binding protein Promotes uterine contractions Lactation And contributes to the second stage of labor in pregnancy Suckling Initiates action potentials in afferent nerve fibers that ultimately stimulate the release of oxytocin from the neurohypophysis. Unknown function. Oxytocin is present in males and females, but its physiological effects are known only for females. The adrenal gland Each gland consists of a yellow outer cortex, and a grey inner medulla zona glomerulosa zona fasciculata zona reticularis Zona Glomerulosa Zona Fasciculata 51 Chem PPT Flashcards, Unit 4 Name the innermost a zone that contains irregular looking cells with little lipid content? What are the three major classes of steroid hormones secreted by the adrenal cortex? What are steroid hormones? CPPP is an abbreviation for? Where are steroid hormones primarily synthesized? What is the major site for steroid metabolism? Where are steroid hormones stored in the body? What is the function of aldosterone? Name the sites where mineralocorticoids can bind to in order to promote sodium reabsorption and potassium and hydrogen ion excretion? The production and secretion of aldosterone are regulated by? What is the primary carrier of aldosterone? Major glucocorticoid synthesized from cholesterol in the zona fasciculata and reticularis of the human adrenal cortex. Cortisol is principally bound and transported to corticosteroid binding globulin (CBG) and is metabolized and conjugated where? Between what percentages of cortisol is carried by CBG? What percentage of cortisol is loosely bound to albumin, and the percentage of unbound (free). Glucocorticoids bind to the glucocorticoid receptor (GR) which can be found where? True or false Glucocorticoids have multiple effects on metabolism of glucose and carbohydrates, Zona Reticularis Mineralocorticoids Aldosterone Glucocorticoids Cortisol Adrenal androgens Dehydroepiandrosterone (DHEA) Androstenedione They are steroids that work as hormones Cyclopentanoperhydrophenanthrene. The basic structure to the nucleus of steroid hormones. Steroid hormones are synthesized primarily from cholesterol in the adrenal glands and gonads The liver Steroid hormones are not stored in hormoneproducing cells and therefore must be produced as needed Regulate salt homeostasis (sodium conservation and potassium loss) and extracellular fluid volume Cytoplasmic mineralocorticoid receptor (MR) in the distal convoluted tubule (DCT) Collecting ducts of the nephron, colon, and salivary glands renin in angiotensin system Albumin Cortisol In the liver 80% and 90% 7% loosely bound to albumin and 2%-3% is unbound(free) Found in many tissues including lymphocytes, hepatocytes and bone. true 52 Chem PPT Flashcards, Unit 4 increases protein catabolism and have several effects on lipid metabolism True or False Glucocorticoids also are powerful antiinflammatory hormones. Cortisol release is controlled through what type of system? Provide androgenic effects through their peripheral conversion to testosterone, which in turn binds to the androgen receptor (AR). True or False Between ages 7 and 8, the urinary excretion of 17 ketosteroids (the breakdown products of adrenal androgens) increases as an early sign that puberty will begin in the coming 3 to 5 years True or false DHEA and its sulfated form, DHEA-S, and estradiol are predominantly bound to albumin, whereas testosterone and dihydrotestosterone (DHT) are mostly bound to sex hormonebinding globulin (SHBG). How do we measure 17- hydroxycorticosteroids (17-OHCS)? 17-hydroxyprogesterone, 11-desoxycortisol are 17-ketogenic steroids. Cortisol also an 17-ketogenic steroid can be measured by? What is a Adrenocorticotropic Hormone (ACTH) Stimulation (Cosyntropin) Tests? Cosyntropin is given to a patient with a low baseline cortisol, what if cortisol level increases? What if cortisol level does not change? A direct and selective test of anterior pituitary gland function. True hypothalamic-pituitary-end organ negative feedback system. Androstenedione true true Measured by the Porter-Silber reaction Measured by Zimmermann reaction Designed to document the functional capacity of the adrenal glands to synthesize cortisol. The test determines whether the adrenal glands are responsive to ACTH. If cortisol level increases the problem lies with the anterior pituitary (secondary adrenal insufficiency) If cortisol level does not change, problem lies in the adrenal cortex (primary adrenal insufficiency) Corticotropin-Releasing Hormone (CRH) Stimulation Test Injection of ovine CRH stimulates ACTH secretion in healthy subjects within 60 to 180 minutes; glucocorticoids inhibit this effect (as in cases of Cushing syndrome) 53 Chem PPT Flashcards, Unit 4 What test is used to test the integrity of the hypothalamic pituitary adrenal axis? An indirect test of hypothalamic pituitary adrenal axis function involves the administration of metyrapone causing a decrease in cortisol The decrease in cortisol is expected to allow an increase in ACTH secretion,What test is this? This type of test involves the administration of potent glucocorticoid dexamethasone, and measuring serum or urine cortisol concentrations to evaluate the hypothalamic response. What test is this? Patients with Cushing syndrome of any cause will fail to suppress their morning plasma cortisol concentration to less than 2 µg/dL in response to a 1 mg dose of dexamethasone administered at 10:00PM. What is a Mineralocorticoid Stimulation Tests Insulin-Induced Hypoglycemia Stimulation Test Insulin is given to produce hypoglycemia which is a physiologic stimulus for release of CRH; plasma ACTH and cortisol concentrations are then measured and will be increased if the hypothalamic pituitary adrenal axis is intact Metyrapone Stimulation Test Dexamethasone Suppression Test Used to determine the function of the reninangiotensin-aldosterone system by stimulating the renin-angiotensin system based on volume depletion maneuvers such as sodium restriction, upright posture or diuretic administration. A normal response is a two to threefold increase in plasma renin, indicating that the JGA is responding properly to decreased plasma volume Mineralocorticoid Stimulation Tests What test makes use of either saline infusion, oral salt loading, or mineralocorticoid administration, each of which should suppress the secretion of aldosterone by the adrenal gland What is Adrenal insufficiency (Addison Results from progressive destruction or disease) ? dysfunction of the adrenal glands by an autoimmune process, the systemic disorder, and inborn error of metabolism (endogenous causes), or by an exogenous cause, such as infection. The most common cause of primary adrenal insufficiency is infectious diseases like 54 Chem PPT Flashcards, Unit 4 What is Hypoaldosteronism? Hypoaldosteronism is seen in? Glucocorticoid Excess (Cushing syndrome)is a result of what? What are the characteristics of a person with Glucocorticoid Excess (Cushing syndrome)? Exogenous Cushing syndrome is a caused of what? What are the clinically significant analytes of virilizing adrenal adenomas? A. Increased DHEA-s,DHEA B. Androstenedione C. Testosterone D. All Of The Above DHEA in high concentrations can be found in virilizing ovarian tumors in women. A. True B. False Adenomas can produce Aldosterone? A. True B. False Conn Syndrome has several symptoms that are clinical in nature. Identify two of them. A. Increased rennin B. HypoKalemic Alkalosis C. Hypertension tuberculosis, fungal infections and cytomegalovirus infection. Deficient aldosterone production occurring in conditions other than Addison disease. Seen in patients with: inadequate production of renin by the kidney which leads to secondary aldosterone deficiency (hyporeninemic hypoaldosteronism) inherited enzyme defects in aldosterone biosynthesis acquired forms of primary aldosterone deficiency (post-surgical or due to heparin therapy) Endogenous Cushing syndrome is a result of autonomous excessive production of cortisol. Characteristic clinical features include truncal obesity, moon facies, a buffalo hump on the upper back below the neck, supraclavicular fat pads, myopathy, hypertension, hirsutism, hypokalemic alkalosis, carbohydrate intolerance, secondary osteoporosis, disturbed productive function and neuropsychiatric symptoms. Exogenous Cushing syndrome is caused by excessive oral or parenteral glucocorticoid therapy. D A B B and C 55 Chem PPT Flashcards, Unit 4 D. Testosterone Incidentalomas are functioning and malignant. A. True B. False Incidentalomas can be found by using two types of technology. Pick Two. A. MRI B. CT C. None of The Above D. Ultrasound A laboratory can confirm the incidentaloma with what two hormones? A. Aldosterone B. Testosterone C. Cortisol D. GRH Hyperaldosteronism is the oversecretion of what hormone? A. Renin B. Aldosterone C. GRH D. Adrenocortcosteroids Outside stimulus can activate the renninangiotensin system in secondary hyperaldosteronism. A. True B. False Choose two causes of Mineral Corticoid excess. A. Bilateral idiopathic hyperplasia B. Aldosterone producing adenoma C. None of the Above D. All of the Above If the PAC/PRA given range ratio concentration value is from 20-25. Presume: A. Primary Aldosteronism B. Secondary Aldosteronism C. Hypokalemia D. Diastolic hypertension Dictate the four analytes for determining Adrenocortical function. A. Urine, Blood B. Saliva C. Hair D. All of the Above B A and B A and B B True D A and C D 56 Chem PPT Flashcards, Unit 4 Cortisol can be measured in several analytes. Name three. A. serum B. heparinized plasma, EDTA Plasma C. Whole Blood D. A and B Cortisol Concentration is lowest in the morning. A. True B. False Can Cortisol be associated with Stress, Pregnancy, and Hypoglycemia? Free Cortisol can be detected by the following methods including: A. Ultrafiltration, Gel Filtration B. Equilibrium C. Dialysis D. All of the above Should a 24 hour urine specimen be collected with boric acid and refrigerated? For collection of Aldosterone, the patient should be upright for: A. 30-120 minutes during collection B. 30-60 before collection C. 30-120 minutes standing or seated before collection D. 30-120 minutes sedentary EDTA is the preferred tube for collecting the plasma specimen? Can Aldosterone decline after 24 hours stored at room temperature? The most stable long term way to store Aldosterone is: A. Refrigerated B. Frozen C. Urine with boric acid D. All of the above A measurement of 17-OHP is used to diagnose what illness? A. Adrenal Hyperplasia B. Congenital Adrenal Hyperplasia C. Renal Hyperplasia D. None of the Above For 4 days at 4 degrees centigrade can specimens, including unseperated blood of 17OHP can be stored? D B Yes D Yes C Yes Yes D B Yes 57 Chem PPT Flashcards, Unit 4 11 beta desoxycortisol can be measured using what techniques? A. LC-MS/MS B. Immunoassay C. Both options Above D. None of the above For the above analyte what are the preferred specimens? A. Serum B. Plasma C. Urine D. All of the above For rennin activity plus it’s concentration the lab can use.. A. Immunoassays B. Immunoradiometric assays C. Immunochemiluminometric assays D. All of the above RBC’s when hemolyzed cause a problem for rennin activity and concentration measurement. Identify the agent they release. A. Angiotensins B. Potassium C. Calcium D. Hemogloblin Cryoactivation should be avoided at all costs for rennin activity and concentration measurements? The thyroid gland butterfly shaped and located just inferior to the ___. The thyroid gland has 2 lobes connected by the ___. The thyroid glands secretory unit is the ___. The thyroid gland produces two hormones: C What is the butterfly-shaped gland situated just below the “Adam's Apple” or larynx? The thyroid gland is composed of two lobes connected by a narrow band of thyroid tissue called _______. What is the secretory unit of the thyroid gland? Thyroid follicle is also known as _____ What is thyroid hormone T3? What is thyroid hormone T4? Thyroid gland D D A Yes larynx isthmus Follicle or acini Triiodothyronine (T3) Tetraiodothyronine or Thyroxine (T4) Isthmus Thyroid follicle Acini Triiodothyronine Tetraiodothyronine or thyroxine 58 Chem PPT Flashcards, Unit 4 Thyroid gland contains 2 cell types: Which cell type produces the hormones T3 and T4? Which cell type produces the hormone calcitonin ? What is a glycoprotein in which the thyroid hormones are stored in the thyroid gland? Biological function of Thyroid Gland: T4 T3 FT4 FT3 TSH rT3 What is the basic element involved in the synthesis of thyroid hormones. What is organification? What are first two steps of organification? What are the second two steps of organification? Follicular cells Parafollicular cells Follicular cells Parafollicular cells Thyroglobulin - Control basal metabolic rate and calorigenesis\ -Enhance mitochondrial metabolism and sensitivity of adrenergic receptors to catecholamines -Stimulate neural development, adrenergic activity, promote sexual maturation -Increase synthesis and degradation of cholesterol and triglycerides, stimulation of protein synthesis and carbohydrate metabolism -Increases the requirement for vitamins, and calcium and phosphorus metabolism Total thyroxine Total triiodothyronine Free thyroxine Free triiodothyronine Thyrotropin (thyroid stimulating hormone) Reverse triiodothyronine Dietary Iodine The process of biosynthesis of thyroid hormones 1) Trapping of circulating iodide by the thyroid gland 2) Incorporation of iodine into thyroglobulin tyrosines producing monoiodinated tyrosines (MIT) and the di-iodinated tyrosines (DIT) 1) Coupling of two iodinated tyrosyl residues to form the thyronines (T4 and T3) within the protein backbone of 59 Chem PPT Flashcards, Unit 4 The normal thyroid gland produces about __% T4 and about __% T3. However, T3 possesses about four times the hormone “strength” as T4. Free (unbound) T4 (FT4) is the primary or secondary secretory product of the normal thyroid gland? What is T4? Which is the most predominant form of thyroid hormone? What percentage of T4 is converted to T3? What is T3? Which thyroid hormone is more physiologically active and more potent that T4? T3 acts as what kind of regulator? When T4 and T3 are in circulation, which carrier proteins are they bound to? What is TBG What is TBPA What is TTR What is TBA What percentage of the above proteins are bound to T4? What percentage of the above proteins are bound T3? How are thyroid hormones regulated? Thyrotropin-releasing hormone (TRH) is released from what? Thyroid stimulating hormone (TSH) is from what? Thyroid hormones are produced from? How does the biostnthesis of thyroid hormones occur? the thyroglobulin (Tg) protein in the follicular lumen Endocytosis followed by proteolytic cleavage of thyroglobulin (Tg) releases the iodothyronines into the circulation 80% T4 and 20%T3 FT4 is the primary secretory product Tetraiodotyronine Thyroxine T4 80% Triiodotyronine T3 Predominant thyroid negative feedback regulator TBG TBPA TTR TBA Thyroxine-binding globulin Thyroxine-binding prealbumin Transthyretin Thyroxine-binding albumin 99.97& 99.7% Negative feedback system from hypothalamus from pituitary from follicular cells of thyroid glands • The biosynthesis of thyroid hormones occurs by a process termed “organification”, which involves: • 1. Trapping of circulating iodide by the thyroid 60 Chem PPT Flashcards, Unit 4 gland • 2. Incorporation of iodine into thyroglobulin tyrosines producing monoiodinated tyrosines (MIT) and the diiodinated tyrosines (DIT) • 3. Coupling of two iodinated tyrosyl residues to form the thyronines (T4 and T3) within the protein backbone of the thyroglobulin (Tg) protein in the follicular lumen. What is the percentage of T3 and T4 that the thyroid gland produces? What is the difference of T3 and T4 and their functions? • Endocytosis followed by proteolytic cleavage of thyroglobulin (Tg) releases the iodothyronines into the circulation. • The normal thyroid gland produces about 80% T4 and about 20% T3, however, T3 possesses about four times the hormone "strength" as T4. • Free (unbound) T4 (FT4) is the primary secretory product of the normal thyroid gland. • T4 (Tetraiodotyronine, Thyroxine) • most predominant form 80% is converted to • T3 61 Chem PPT Flashcards, Unit 4 How does T3 and T4 circulate in the blood? What is the regulation and control of thyroid hormones? What are the different thyroid disorders? • T3 (Triiodotyronine) • more physiologically active (more potent than T4) • predominant thyroid negative feedback regulator • T4 and T3 in circulation are bound to carrier proteins • Thyroxine-binding globulin (TBG) • Thyroxine-binding prealbumin (TBPA; transthyretin [TTR]) • Thyroxine-binding albumin (TBA) • These proteins bind 99.97% of T4 and 99.7% of T3, thus very small fraction is unbound and available for biological activity. • Regulation and control • Controlled by Negative Feedback System • Thyrotropin-releasing hormone (TRH) from hypothalamus • Thyroid stimulating hormone (TSH) from pituitary Thyroid hormones from follicular cells of thyroid glands • Euthyroid • having normal thyroid function • Hyperthyroidism (Thyrotoxicosis) • a condition caused by excessive production of iodinated thyroid hormones 62 Chem PPT Flashcards, Unit 4 What are the different thyroid disorders? • Hypothyroidism • a condition of deficient thyroid gland activity • Thyroiditis • a condition characterized by inflammation of the thyroid gland Thyroid storm • a life-threatening condition that develops in a minority of cases of untreated thyrotoxicosis (hyperthyroidism, or overactive thyroid) Toxic multi-nodular goiter • a condition in which the thyroid gland contains multiple lumps (nodules) that are overactive and that produce excess thyroid hormones. Also known as Parry disease and Plummer disease. • • What is a goiter? What is sporadic goiter? Name hypothyroidism disorders? - An enlargement of the thyroid gland that causes a swelling in the front part of the neck - Occur when the thyroid gland produces either too much thyroid hormone (hyperthyroidism or toxic goiter) or not enough (hypothyroidism or non-toxic goiter). Can form if the diet includes too many goiterpromoting foods, such as soybeans, rutabagas, cabbage, peaches, peanuts, and spinach. These foods can suppress the manufacture of thyroid hormone by interfering with the thyroid's ability to process iodide. -Myxedema -Cretinism -Primary hypothyroidism Endogenous causes Exogenous causes 63 Chem PPT Flashcards, Unit 4 What are characteristics of Myxedema? What is Cretinism? What are some differences between Dwarfism and Cretinism? What are the clinical symptoms of hypothyroidism? What are the physical signs of hypothyroidism? What endogenous disorders cause primary hypothyroidism? -Central hypothyroidism Secondary hypothyroidism a severe form of hypothyroidism in which there is accumulation of mucopolysaccharides in the skin and other tissue, leading to a thickening of facial features and a doughy induration of the skin. Is the archaic term used to describe severe hypothyroidism that develops in the newborn period. Appropriate term is congenital hypothyroidism Dwarfism is caused by hypopituitarism and Cretinism is cause by hypothyroidism. Dwarfism has decreased Growth Hormone secretion while cretinism has decreased T4 and T3. Dwarfs are mentally normal while patients with cretinism have a low IQ. Mental dullness, somnolence, increased sleeping, lethargy, easy fatigability, hoarseness, hair loss, weight gain, cold intolerance, menstrual irregularities, infertility, growth failure, delayed puberty in adolescents, constipation, muscle weakness or cramps, and depressed affect or frank clinical depression. Bradycardia, decreased pulse pressure, cool and/or dry skin, puffy eyes, loss of the outer lateral eyebrows, delayed relaxation phase of reflexes, myopathy, carotenemia, occasional galactorrhea, short stature in affected children, radiologic evidence of delayed bone age in children, congestive heart failure, coma may rarely occure (severe hypothyroidism) Autoimmune thyroid diseases such as Hashimoto thyroiditis, atrophic thyroiditis, late-stage graves disease, and postpartum thyroiditis. Inborn errors in thyroid hormone biosynthesis such as Na+/ iodine pump dysfunction, inadequate organification/ iodination-TPO dysfuntion, defective thyroglobulin, deiodinase deficiency, and pendred syndrome-hypothyroidism and deafness. Developmental disorders involving the thyroid gland such as congenital hypothyroidism: aplasia, hypoplasia, and ectopic thyroid: lingual thyroid, thyroglossal 64 Chem PPT Flashcards, Unit 4 What exogenous disorders cause primary hypothyroidism? For primary hypothyroidism what happens to T3, T4, FT4I, and T3U and TSH. In primary hypothyroidism, why does TSH concentration increase when concentrations of T3, T4, FT4I, and T3U? For secondary hypothyroidism what happens to T3, T4, FT4I, and T3U and TSH? In secondary hypothyroidism, why do the concentrations of T3, T4, FT4I, T3U and TSH decrease? What is Hypothyroidism? What disease caused by Hypothyroidism? What is Hashimoto’s Disease? duct cyst. Consumptive hypothyroidism (increased metabolism of T4, and T3 by tumors) Iodine excess/ deficiency, drugs, thionamides, lithium, nitroprusside, amiodarone, biologicals like interferon and interleukin-2, dietary goitrogens, radiation-induced hypothyroidism, surgical removal of the thyroid gland, and viral or bacterial thyroiditis. Concentrations of T3, T4, FT4I, and T3U decrease while TSH concentration increases. Due to the negative feedback mechanism, the low concentrations of T3, T4 is sensed by the pituitary gland causing it to secrete more TSH in order for the thyroid to secrete more T3 and T4, however since the thyroid is not functioning properly T3 and T4 are not secreted, which causes more secretion of TSH by the pituitary gland. Concentrations of T3, T4, FT4I, T3U and TSH decreases. Because the pituitary gland is not properly functioning causing a decrease in TSH secretion, which in turn causes the decrease in T3 and T4 secretion by the thyroid. A Condition of deficiency thyroid gland activity leading to lethargy, muscle weakness, and intolerance to cold. Hashimoto’s Disease (Hashimoto’s thyroiditis) Is an autoimmune disease, a disorder in which the immune system turns against the body's own tissues. In people with Hashimoto's, the immune system attacks the thyroid, leading to hypothyroidism. People who have family members who have thyroid disease or other autoimmune diseases usually develops the disease. (Genetic component) Hashimoto's affects about seven times as many women as men, suggesting that sex hormones may play a role. Furthermore, some women have thyroid problems during the first year after having a baby. 65 Chem PPT Flashcards, Unit 4 What is autoimmune disease? Immune system disorders cause abnormally low activity or over activity of the immune system. In cases of immune system over activity, the body attacks and damages its own tissues. For example, Immune deficiency diseases decrease the body's ability to fight invaders, causing vulnerability to infections. What is thyroid disease? Any dysfunction of the butterfly-shaped gland at the base of the neck (thyroid). – Autoimmune hypothyroidism – Inborn errors in thyroid hormone biosynthesis – Developmental disorders – Iodine deficiency or excess – Drug-induced – Surgical and radiation-induced – Viral or bacterial thyroiditis – Central hypothyroidism – Subclinical hypothyroidism Monocarboxylate Transporter (MCT) 8 mutation (Allan-Herndon-Dudley syndrome) Hashimoto’s disease, which leads to destruction of the Thyroid follicular cells through a cell-mediated autoimmune Process, Initially, the gland is usually enlarge for instance, goiter Are rare cause of primary hypothyroidism because of Biochemical defects of iodine transport from loss-of-function mutations in sodium iodide symporter transporter system. Worldwide, the most common cause of goiter is iodine deficiency producing endemic goiter with or without nodularity. Excess iodine can cause a transient state of reduces thyroid function. Various drugs effect thyroid function. Surgical removal of TG will produce hypothyroidism. External irradiation of the TG (treatment of lymphoma or Hodgkin Disease) or ingestive iodine also has been What are the other Causes of Hypothyroidism included: What is autoimmune Hypothyroidism? What is the Etiology of Inborn error in thyroid hormone biosynthesis? What is the etiology of Iodine Deficiency or excess? What is the etiology of drug-induced? What is the etiology of surgical and radiationInduced? 66 Chem PPT Flashcards, Unit 4 What is the etiology of Viral or Bacterial Thyroiditis? What is the etiology of Subclinical hypothyroidism? What is the other name for hyperthyroidism/thyrotoxicosis disease? What are the causes of hyperthyroidism/thyrotoxicosis disease? What are the clinical techniques involved in hyperthyroidism treatment? What are endogenous thyroid disorders? What are exogenous thyroid disorders What are clinical symptoms of hyperthyroidism? What are physically sign of hyperthyroidism? What are the specific causes of hyperthyroidism? known to cause hypothyroidism. Although rarely occurring, some (1) viral infections (such as, sub-acute thyroiditis or giant cell thyroiditis), or 2 bacterial infections (acute thyroiditis or abscesses) of TG will seriously damage the TG and lead to hypothyroidism. A persistent elevation in TSH (6 to 12 weeks or longer) in the setting of FT4 concentrations that are repeatedly found within reference interval. Graves' disease Endogenous causes Exogenous causes – Anti-thyroid drugs – Radioiodine ablation Surgical removal of thyroid gland - Autoimmune thyroid disease - Graves disease - Hashitoxicosis - Postpartum thyroiditis - Toxic nodule, multinodular goiter, adenoma Stumi ovari - Thyroid destruction Iodine induced hyperthyroidism Thyroid hormone ingestion (thyrotoxicosis factitia) - Nervousness, erratic behavior, restlessness, sleeplessness - Weightloss, excessive sweating - Heat intolerance - Menstrual irregular Diarrhea - Tachycardia - Atrial arrhythmia - Systolic murmurs - Increased pulse pressure - Bounding pulse - Warm/ damn skin - Tremors - Increased reflexes Eyelid retraction T3 toxicosis, graves’ disease, hashimoto’s disease and postpartum thyroiditis, toxic nodular or multinodular goiter, gain-of67 Chem PPT Flashcards, Unit 4 What is Graves’ disease also known as? What is Graves’ disease or hyperthyroidism? What are the signs and sympptomes of hyperthyroidism? What are the hyperthyroidism’s laboratory evaluation? Graves disease is an autoimmune disorder that involves ? What are some of the Grave’s disease symptoms in the human body Thyroid hormone affect a numerous of body funtions includind ? The primary treatment goals for graves disease function mutations in thyroid-stimulation hormone receptor, central hyperthyroidism, human chorionic gonadotropin, iodineinduced hyperthyroidism, thyroid-storm and apathic hyperthyroidism, subclinical hyperthyroidism, pregnancy and other exogenous causes. Toxic diffuse goiter and Flajani-BasedowGraves disease. Is an autoimmune disease that affects the thyroid, resulting in hyperthyroidism and an enlarged thyroid. Include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea, and weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye problems such as bulging, a condition known as Graves' ophthalmopathy. About 25% to 80% of people with the condition develop eye problems. • Laboratory Evaluation of Hyperthyroidism: • ↑ FT3 • ↑ FT4 • ↑ FT4I • ↑ T3U • ↑ THBR (thyroid hormone binding ratio) • ↓ TSH Over activity of the throid gland (hyperthyroidism) Bulging eyes Sweating Thick red skin usually on the shings or tops of the feet Enlarge thyroid Metabolism Heart and nervous system function Body temperature Muscle strength Menstrual cycle Tremor Exophthalmos Inhibit the production of thyroid hormones 68 Chem PPT Flashcards, Unit 4 are to ? Some treatment for Graves’s disease are ? Lessen the severity of symptoms Anti thyroid medication Radioactive iodine Surgery Disorders associated with thyroid hormone excess or deficiency in absence of thyroid disease What happens in primary hypothyroidism? What happens in primary hyperthyroidism? What hormone is the American Thyroid Association’s recommended for screening test? What is the method for Measurement of Thyroid Stimulating Hormone (TSH)? -Significant nutritional deprivation -Acute severe illness -Chronic illness TSH increased, FT4 decresed. TSH decreased, FT4 increased. Measurement of Thyroid Stimulating Hormone (TSH) Measurements are done using the two-site "sandwich" heterogenous immunoassay involving enzyme, fluorometric substrate or chemiluminescent labels. A. TSH Both serum and plasma are used for what type of measurements. TSH is stable for how many days at 2 to 8°C, and for at least 1 month when stored frozen. For newborn screening, whole blood may be collected by heel puncture how many hours after birth. Secretion of TSH is circadian with big concentrations occurring between ______(time of day), and the lowest between _______(time of day). Measurement is done using electron capture gas chromatography, high performance liquid chromatography, and isotope dilution tandem mass spectrometry. This is the Measurement of what? What is the preferred specimen (EDTA and heparin plasma can also be used) for Total Thyroxine . Because total T4 alone provides limited clinical information, FT4 measurements are preferred. True or False? What does T3 stand for? What is the techniques of choice to measure T3 in body fluids predominantly serum or plasma? Give 2 examples. Serum specimens should be tested within ______ hours of collection. 5 days 48 to 72 1. 2:00 to 4:00 AM 5:00 to 6:00 PM Total Thyroxine (T4) Serum True Triiodothyronine Immunoassays Radio immunoassay Non-isotopic immunoassays 24 69 Chem PPT Flashcards, Unit 4 What temperature must serum specimens be stored at after 24 hours? What does ‘rT3’ stand for? Measurement are done, using which immunoassay? True or False: rT3 measurement has limited diagnostic value. True or False: The diagnosis of non-thyroidal illnesses can usually be established without measuring rT3. 2 to 8°C Reverse Triiodothyronine Radio immunoassay True True What are the methods of measurement of Free Thyroid Hormones? Direct assays •serve as reference methods –Direct Equilibrium Dialysis –Ultrafiltration Indirect or estimate assays •for general laboratory use –Two-step and One-step immunoassay What type of measurement are used in •competitive, heterogenous method Thyroxine Binding Globulin (TBG)? •measurement of bound conjugate by chemiluminescence •enhance microparticle turbidimetry Measurement of Thyroglobulin (Tg) is done by: Competitive and noncompetitive immunossasys What are the 4 autoantibodies of clinical interest Thyroid-stimulating antibodies which are found in thyroid disease? (TSAb), TSH receptor-binding inhibitory immunoglobulins (TBII), Antithyroglobulin antibodies (Anti-Tg Ab) Antithyroid peroxidase antibody (Anti-TPO Ab) Of the 4 clinically important autoantibodies Anti-TPO Ab has emerged as the most which is generally the most useful? generally useful marker for the diagnosis and management of autoimmune thyroid disease Determination of Thyroid Autoantibodies Measurement includes: includes what tests/measurements? Indirect immunofluorescence Agar gel diffusion precipitin technique Agglutination (hemagglutination or latex particle agglutination) RIA (Radio immunoassay) Complement fixation ELISA techniques Chemiluminescence based immunometric assays 70 Chem PPT Flashcards, Unit 4 Please refer to picture below. After screening using TSH, if the result of the TSH is elevated what hormone is needed to be tested in order to determine the type of thyroidism does the patient has? FT4 71