Laboratory Medicine

Laboratory tests
1. Routine Tests
  1. on blood and urine
  2. Blood with or without anticoagulants
    1. Serum
      1. no anticoagulant
      2. general usage
      3. defibrinated plasma
        cannot be used to study coagulation factors
    2. Plasma
      1. EDTA
        Coagulation factors, RBCs, Lipids and lipoproteins
      2. Lithium Heparin
        General usage
      3. fluoride oxalate
        glucose, lactate
2. Specialized Tests
  1. sent to specialized reference laboratories
  2. Examples
    1. VIP
    2. PTHrP
    3. DNA analysis
    4. Troponin
3. Emergency Tests
  1. samples obtained during surgery or as ER work up
  2. intraoperative testing of PTH
    1. determine if PTH-secreting adenoma was removed
4. Qualifications of a "Good" Test
  1. Precision
    1. same result on same sample every time
  2. Accuracy
    1. how close measured value is to true value
  3. Specificity
    1. measures incidence of "true negative"
    2. Spec = (TN/(TN+FP)) * 100
  4. Sensitivity
    1. incidence of true positives
    2. Sen = (TP/(TP+FN)) * 100
  5. Predictive Value
    1. Positive Test
      1. = (TP/(TP + FP)) * 100
    2. Negative Test
      1. = (TN/(TN + FN)) * 100
Water and Sodium
1. Water in comparments
  1. Intracellular volume
    1. potassium most important here
  2. Extracellular volume
    1. interstitial compartment
    2. Plasma
    3. sodium most important here
2. 70 kg man has 4200 mmol Na+
  1. [Na+] ~ 135-145 mmol/L
    1. Depends on Kidneys and hormone
      1. Thirst
      2. ADH
      3. Aldosterone
      4. Atrial Natriuretic Peptide
3. Sodium is a part of...
  1. Acid-Base balance
  2. Cell membrane polarity
  3. Osmolality of body fluids
    1. Sodium is primary determinant
    2. Os = (2*Na)+(glu/18)+(BUN/2.8)
4. Hyponatremia
  1. Dilutional
    1. increased water intake
    2. infusion of water
    3. decreased excretion of water
    4. Hypoproteinemia
    5. Shift of water from cells into ECV
    6. SIADH
  2. Depletional
    1. Gastrointestinal Loss
      1. Vomiting, Diarrhea, sequestration of fluid in intestine, fistulas
    2. Renal Loss
      1. Diabetes mellitus, hypercalcemia, salt-wasting kidney disease, diruetics, Addison's disease
    3. Dermal Loss
      1. Burns
  3. [Na+] < 136 mmol/L
  4. Symptoms
    1. usually asymptomatic
    2. depressed transmission of neural or neuromusclar signals
5. Hypernatremia
  1. [Na+] > 150 mmol/L
  2. Water Loss
    1. Renal loss of water
      1. Diabetes insipidus (central or nephrogenic), renal tubular necrosis, diuretics
    2. GI loss of Water
      1. Diarrhea, vomiting, nasogastric suction tube, osmotic cathartic agents
    3. Dermal Loss of water
      1. Sweating, burns
  3. Excessive Sodium Intake or Retension
    1. Adrenal cortical lesions
      1. hypercortisolism
    2. Corticosteroids
    3. Infusion of sodium-rich solutions
  4. Frequently from Dehydration
Chloride
1. Major extracellular anion
  1. linked to intake, excretion and metabolism of Na+
2. [Cl-] ~ 98-106 mmol/L
3. Hyperchloremic metabolic acidosis
  1. depletion of bicarb, replaced by organic anions
    1. can be filled by Cl-
      1. no hypernatremia
4. Hypochloremic metabolism alkalosis
  1. loss of Cl- in GI tract, filled with bicarb
Potassium
1. intracellular cation
  1. [K+]~ 3.5-5.0 mmol/L
2. Maintained by Kidneys
  1. excrete 100 mmol a day
  2. secreted and diffusion
  3. aldosterone promotes secretion of K+
  4. Cellular States
    1. Normal Cell
      1. Higher K+ in cell
    2. Damaged Cell
      1. Hyperkalemia
    3. Acidosis
      1. Hyperkalemia
    4. Alkalosis
      1. Hypokalemia
  5. Insulin promotes cellular uptake of K+
3. Maintained by Na+/K+ ATPase
4. Hypokalemia
  1. increased loss of K+ in urine
  2. redistribution of K+ into cells
  3. GI loss
  4. Symptoms
    1. Cardiac Arrhythmias
    2. Neuromuscular
      1. weakness and hypotonia
    3. Slow GI peristalsis
    4. decreased concentrating capacity of the kidneys
5. Hyperkalemia
  1. reduced excretion
  2. Massive tissue injury or cell lysis
  3. Redistribution from ICV to ECV
  4. Symptoms
    1. Cardiac Arrhythmias
Acid Base Balance
1. Buffer system
  1. H+ is buffered using bicarb to maintain constant pH
  2. Kidneys can regenerate bicarbonate
    1. Can also remove H+
2. Metabolic Acidosis
  1. accumulation of H+, reduced HCO3
    1. compensate by exhaling CO2, decreased pCO2
  2. Loss of bicarb
    1. DI tract through diarrhea, intestinal, pancreatic, biliary drainage
  3. inability to excrete H+
    1. Kidney failure, hypoaldosteronism
  4. Excessive endogenous acids
    1. diabetes mellitus
  5. Ingestion of fixed acids
  6. high anion gap (sometimes)
    1. adding acid does
3. Metabolic Alkalosis
  1. loss of H+ or HCO3 retention
    1. reduced breathing
  2. ECV contraction
  3. Potassium Deficiency
  4. Mineralocorticoid Excess
4. Respiratory Acidosis
  1. retention of CO2
    1. kidneys retain HCO3
    2. Excess CO2 is buffered as HCO3
      1. Increased H+ in blood
  2. hypoxia
  3. Symptoms
    1. increased blood flow to brain, reduced cardiac output, pulmonary HTN
5. Respiratory Alkalosis
  1. excessive loss of CO2
    1. increase excretion of HCO3
    2. From hyperventilation
  2. Symptoms
    1. hypocapnia, light headedness, syncope
    2. perioral and peripheral paresthesia
Calcium
1. Extracellular Ion
  1. Concentration depends on pH of blood, [albumin],
  2. reduce during respiratory alkalosis
2. [Ca +2] ~ 8.4 - 10.2 mg/dL (2.2-2.6 mmol/L)
  1. Free, protein bound, anion bound
    1. Albumin and globulins are calcium binding proteins
  2. increased [protein bound Ca2+]
    1. Dehydration
    2. Paraproteinemia
  3. Hypoalbuminemia
    1. low total serum calcium with no clinical evidence
3. Hypocalcemia
  1. caused by hypoalbuminemia
  2. Alkalosis
    1. less free H+, albumin will bind calcium more
  3. With hyperphosphatemia
    1. Hypoparathyroidism
      1. surgery or DiGeorge Syndrome
    2. Chronic Renal failure
      1. Inadequate Vit D hydroxylation
    3. Hypomagnesemia
      1. normally help form PTH
  4. with hypophosphatemia
    1. Inadequate intake of Vit D
    2. Rickets
    3. Intestinal Malabsorption
    4. Renal or Liver Disease
    5. Drug related
  5. Neonatal
    1. Inborn errors of met.
  6. Symptoms
    1. Neuromuscular numbness, parestheisa, spasms,
    2. abnormal heart rhythm, prolonged QT
    3. Lack of alertness, convulsions, loss of consciousness
    4. laryngeal stridor
4. Hypercalcemia
  1. Hyperparathyroidism
    1. Primary
      1. parathyroid adenoma or hyperplasia
    2. Secondary
      1. chronic renal disease
    3. Tertiary
      1. becomes independent of [Ca2+]
  2. Neoplasia
    1. malignant tumors
    2. bone metastases
    3. PTHrP
    4. Multiple Myeloma and Lymphoma
  3. Vitamin D intoxication
    1. Granulomatous Diseases
      1. TB, sarcoidosis, fungal infections
  4. Hyperthyroidism
  5. Usually asymptomatic
    1. Renal: polyuria, polydipsia, renal calculi, nephrocalcinosis
    2. Muscle/Skeleton: pain, fractures, weakness,
    3. Neuro: weakness, fatigue
    4. GI: abdominal pain, anorexia, constipation
    5. Cardio: arrhythmia, ECG, arrest
Phosphorus
1. Mostly in bones and teeth, some inside cells (little in serum)
2. phosphates filtered in kidney are reabsorbed
3. Hypophosphatemia
  1. inadequate absorption or increased loss or shiftfrom compartment
    1. antiacids may block absorption
  2. alkalosis
  3. increased insulin
  4. Symptoms
    1. muscle weakness, cardiac arrhythmia, confusion
    2. reduction of 2,3-diphosphoglycerate in RBC
4. Hyperphosphatemia
  1. chronic renal failure preventing excretion
    1. reduces calcium
  2. Massive Cell Lysis
  3. Leads to hypocalcemia and metastatic calcification
Proteins
1. plasma proteins mostly from the liver
  1. Immunoglobulins are the exception
2. Albumin and Globulin
  1. 3:1 ratio normally
3. Electrophoresis
  1. will separate into 5 bands
    1. fetal and newborn blood have 6
      1. prealbumin
4. Albumin
  1. oncotic protein in blood
  2. buffer
  3. source of amino acids for other proteins
  4. transport protein for calcium, FFA, bilirubin, hormones, drugs, etc
  5. antioxidant
  6. regulator of capillary permeability
5. Others
  1. alpha1-globulin
    1. alpha-antitrypsin
      1. serine protease inhibitor
    2. alpha fetoprotein
      1. major fetal protein,
  2. alpha2-globulin
    1. alpha2-macroglobulin
      1. protease inhibitor
      2. increase in nephrotic syndrome
    2. haptoglobin
      1. binds free hemoglobin
    3. ceruloplasmin
      1. ferroxidase activity, transports copper and iron
      2. acute phase protein
  3. beta-globulin
    1. transferrin
      1. iron-transporting protein
    2. complement factors C3 and C4
      1. inflammatory and immune reaction
    3. B2-microglobulin
      1. light chain of class 1 leukocyte antigen
    4. Fibrinogen
      1. coagulation when fibrin
  4. gamma-globulin
    1. immunoglobins
    2. C-reactive protein
      1. present during infection, rheumatoid arthritis, etc.
6. Diagnostic Proteins
  1. Aminotransferases
    1. Aspartate aminotransferase
    2. Alanine Aminotransferase
    3. leak out of damaged livers
  2. Alkaline phosphatase
    1. healthy: from bone
    2. marker of biliary obstruction
  3. Lactate Dehydrogenase
    1. high in neoplastic states
    2. cell damage
  4. Creatine Kinase
    1. muscle injury
    2. CK-MB in myocardial infarction
  5. Blood Urea Nitrogen
    1. high in renal failure, shock, volume depletion
    2. GI bleeding, stress, drugs, corticosteroids
    3. Low: starvation, liver failure, polyuria,
  6. Creatinine
    1. kidney failure
Lipids and Lipoproteins
1. complexed with apoproteins in whater
  1. chylomicrons, VLDL, LDLs, HDLs
2. Hyperlipidemia
  1. primary (genetic)
    1. elevation of cholesterol and TGs
  2. secondary dislipoproteinemias
    1. from diabetes, obesity, alcoholism, hypothyroidism, nephrotic syndrome, biliary obstruction, antihypertensive drugs
Carbohydrates
1. stored as glycogen
2. Hyperglycemia
  1. Diabetes Mellitus
3. Hypoglycemia
  1. overtreatment of diabetes

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Laboratory Medicine

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	Created by Jeff Amos over 10 years ago