Biological causes of variation of test results Midiiielii Knillkuvü, 1YLD I) b p iľľ'iiii biií uí Ľi u bk biin^iľy F u buky uí 1VJ b ill ťin b \yia^iíľjk oni vbľúíy • The discrimination between normal and abnormal results is affected by various physiological factors which must be considered when interpreting any given result. • These include: AGE SEX OF THE PATIENT PREGNANCY MENSTRUAL CYCLE RACE EFFECTS OF ENVIRONMENTAL FACTORS SEASONAL INFLUENCES CIRCADIAN VARIATION POSTURE OF THE PATIENT EFFECTS OF EXERCISE EFFECTS OF DIET SMOKING AGE • different reference ranges for neonates, children, ad u Its, and the elderly • Newborn infant: • the body fluids reflect: • trauma of birth • the changes related to adaptation to an independent existence • maturity of the infant at birth (HbA - HbF) • The serum activities of several enzymes (CK, AST, GMT) are high. • The concentration of bilirubin rises following birth and peaks about the 3rd to 5th day of life = physiological jaundice of the newborn. Examples • total body water: newborn 80% of body weight, the elderly 50% • most important enzyme activities (ALT, AST, ALP, GMT, LD, HBD, CK) higher in childhood (growth and development) • ALP lm. < 55 (jmol/l • K/S 0-1 m. 4.0-7.7 mmol//l adults 3.8 - 5.5 mmol/l 14 Examples • Fe /S 0-1 m. 9 - 36 umol/1 adults 10 -25 umol/1 • ferritin /S <18y. 15-120 ug/l 18-45 y. 55y. d 30-400 ug/l ? 30-120 ug/l • total bil/S Istweeek < 150 (300) umol/1 adults < 20 umol/1 • Creatinin 0-2 d. 20-140 umol/1 2-7 d. 17-100 umol/1 7-14 d. 15-80 umol/1 14-28 d. 10-70 umol/1 10 y. 35-110 umol/1 • The same values in both children and adults: pH and osmolality SEX OF THE PATIENT j 'Ľií'íšľšm valila siříce pub es c en c e ücciirs • sex hormones and their metabolites • Fe/S, ferritin • hemoglobin • lipoproteins • urea, Creatinin • uric acid • homocysteine • ALT, AST, ALP, GMT, LD, CK • CRP • generally higher values in males PREGNANCY j Cküiivs Dl íh'ô V ill 11 b^l > Estradiol FSH LH ► Progesterone ► Prolactin hCG PREGNANCY j líi^ľbuzbú. pIíiDJJiíi volumu —' hbinüüiluilüü - f in glomerular filtration rate (f creatinine clearance) - | in total urine volume, mainly during the 3rd trimester (25%) » t in serum apolipoproteins, TG and chol ■> t in ALP activity » t in ceruloplasmin, T4s acute phase proteins (CRP) synthesis ► relative deficiency of Fe, ferritin ► 4 hey MENSTRUAL CYCLE j Iiíiliíbíi'íu íiiíúíiiy: ♦ Estradiol ♦ FSH ♦ LH ♦ Progesterone ♦ Hey, Chol, Fe RACE Examples: Afroamericans | glucose tolerance than Caucasians Afroamericans t total CK and LD than Caucasians Hispanics and Afroamericans t AFP and hCG Afroamericans t Cu /S Far-east Asians | salivary AIMS EFFECT OF ENVIRONMENTAL FACTORS * geographical location (drinkink water composition, pollution) j iijdtude Effects of altitude ♦ fin: • Haematocrit » (difference sea level -1 400 m.a.s.l. = • Haemoglobin • Erythropoetin • CRP (difference sea level - 3 600 m.a.s.l. = 65%) Increase in htc, Hb, eres Initially, Hb increases as a result of plasma volume decline caused by dehydratatíon (trend not to drink + water lost by hyperventilation + lower humidity), subsequently increased production of eres (- erythropoetin) gives in. fltln 20 n 15j 3> as ICH 5j ü m 4540 m 0 m 4540 m ü m 4540 in Erythropoetin synthesis and erythrogenesis starts to increase in 2 hours after hypoxia occurs. Erythropoetin -t 1 eooum 3 SOU m -i--------------1---------------1--------------1--------------1------------- 2 3 4 5 6' Days in mountains SEASONAL INFLUENCES on the composition of body fluids are small. • Evaluations of seasonal variation are difficult, since they depend on the definition of a season and on the magnitude of temperature change from one season to another. Day-to-day variability in the composition of body fluids is greater in summer than in winter. • Examples: • D vitamin | in summer (lenght of sun exposure) • thyroid hormones I in summer (20%) CIRCADIAN VARIATION • = time when sample was taken • examples: • Cortisol maximal value at 6 a.m. morning 250-650 mnol/l afternoon 50-280 n m o l/l • Fe 30% higher in the morning • creatinine 10-20% higher in the afternoon • STH secreted at midnight POSTURE OF THE PATIENT ♦ head pressure —► redistribution of body fluids • The blood volume of an adult in an upright position compared to an adult in a lying position is typically 600 - 700 ml less. Fluid reduction in plasma is associated with a comparable increase in the plasma protein concentration« • adrenalin and noradrenalin values in an upright position almost 2times higher compared to a lying position blood drawing to the sitting pacient EFFECTS OF EXERCISE • Exercise changes blood levels of all substances that participate in energy metabolism, e.g. glucose, lactate, FA, phosphate, creatinine« • Strenuous exercise can release enzymes from tissues. • Blood pH, oxygen saturation, and venous bicarbonate are decreased. • Long-term exercise increases the concentrations of sex hormones. EFFECTS OF DIET • The sample may be inappropriate if taken when the patient is fasting or after a meal. Define the term f ruling -patient! Fasting patient • didn't eat 10-12 h. during night • was all quiet (didn't ride a bicycle or walk a long time), • didn't smoke, • didn't drink coffee or alcohol or sweetened drinks • blood drawing between 6-9 a.m. EOTE CTS OF DIET • food rich in fats : | TG, chol; I nitrogen compounds (uric acid) • food rich in proteins: t urea, uric acid, phosphates • food rich in saccharides: t ALP, LD; I TG, chol, total proteins • vegetarians: | uric acid, urea, ammonia, total and LDL-chol, TG; t bil; alkalinization of urine (phosphate stones!) EFFECTS OF DIET • immediate food intake: t glc, TG, uric acid, Fe, Na |LD • other examples of diet interferences: • gFOBT test: violation of the blood- and Fe -less diet • clearance determination: insufficient fluic 1 intake EFFECTS OF DIET - LONG-TERM FASTING = FASTING LONGER THAN 24 HOURS • glycogenolysis in liver (—► glc - energy for CNS and eres) • proteolysis in muscles (—► AA for gluconeogenesis) • TG degradation in adipose tissue —► glycerol (-► gluconeogenesis) and FA (direct energy for myocardium, muscles and kidneys + in liver —► keton bodies) • í TG, FA, glycerol • i glc • t bil EFFECTS OF DIET - CAFFEINE CONSUMPTION • phosphodiesterase inhibition —► | cAMP —► t glycolysis —► | energy + alertness of an organism TG cleavage—► f glycerol and FA • | renin and catecholamines (within 3 h) EFFECTS OF DIET - ALCOHOL CONSUMPTION • degradation velocity = 0.15 %o / h • acute Consumption: t TG, aldosterone I prolactin, ADH, Cortisol • chronic consumption: | ALT, AST, GMT; Cortisol, adrenaline, estradiol, uric acid, lactate (MAc) I glc; ketoacidosis • hepatotoxicitv SMOKING • tHbCO(8%) • l vit. Bi2 and Ig • t total Chol and TG, | HDL-chol • f Cortisol, CEA, Pb, Cd • Beware smoking as a risk factor. There is a maxim that doctors should always 'treat the patient, rather than the laboratory report*. Beware of overreacting to the slightfy abnormal result in the otherwise healthy individual