Acid/Base Flashcards
Acid/Base Definitions
Acid - compound donating H+
Base - compound accepting H+
pH - negative log of [H+]
Acid/Base Formula
pH = 6.1 + log HCO3/H2CO3
BUFFERS
- Systems that resist change in pH when acid, base added
- Usually composed of weak acid, conjugate base
- Work best when near equal amounts of each present (within ± 1 pH unit of pKa of weak acid)
ACIDOSIS vs ACIDEMIA
- Acidosis - increase in amount of acid present relative to base
- Acidemia - increase in [H+]
- All persons who are acidemic have an acidosis; not all persons with acidosis have acidemia!!!
- Compensation, mixed acid base disorders may minimize acidemia in presence of acidosis
ANION GAP
- Difference between measured cation (Na+), anions (Cl-, HCO3 -), ~ 6-12 mmol/L
- Measure of relative amounts of other anions (esp. albumin, acid anions), cations (Ca, Mg, immunoglobulins)
- High anion gap = acid anions
- Low anion gap: low albumin +/or high Ig’s (myeloma, AIDS, cirrhosis)
LABORATORY TESTS OF ACIDBASE STATUS
Blood Gases
Electrolytes
Osmotic Gap
Lactate, Ketones
Blood Gases
- Critical for evaluating respiratory component (as pCO2)
- Also allows evaluation of oxygenation
- Measures pH, pCO2, calculates bicarbonate, O2 saturation
ELECTROLYTES
- Total CO2 content = bicarbonate + carbonic acid + carbamino compounds; usually 1-2 mmol/L higher than true bicarbonate
- Also used to calculate anion, osmotic gap
OSMOTIC GAP
- Difference between measured, calculated (2 * Na + BUN/3 + glucose/20) osmolality
- Normal may be up to 10 mmol/L
- Increase indicates uncharged substances; usually alcohols (volatiles), glycols
- Osmotic gap = concentration (in mmol/L)
- Use freezing point depression; vapor pressure osmometers don’t detect volatiles
LACTATE, KETONES
- Product of anaerobic glycolysis; prevent in vitro glycolysis with NaF
- Ketones come from fatty acid metabolism
- Normally, -OH butyrate dominant, not measured in “ketone” assay; as metabolized, “ketones” rise
Acid/Base Disorders
General Concepts
- For board purposes, acid-base disorders occur singly; if compensated, pH near normal but always on proper side (slightly low in acidosis, slightly high in alkalosis)
- Combined disorders always same direction (e.g., metabolic and respiratory acidosis)
- In real life, these rules don’t apply!!
Acid/Base Disorders
General Concepts 2
- In metabolic disorders, pH, pCO2, HCO3 all change in same direction; in respiratory disorders, pCO2, HCO3 change in one direction, pH in opposite
- Anion gap high ONLY with metabolic acidosis (but there are also non-anion gap metabolic acidoses)
Acid/Base Disorders
General Concepts 2
see image
COMPENSATION
- An adaptive response to return pH towards normal by restoring normal ratio of pCO2 to HCO3
- With respiratory disorders, alters renal excretion of HCO3
- With metabolic disorders, alters respiratory rate to change pCO2
METABOLIC ACIDOSIS
Increased anion gap usually due to overproduction; renal failure rare cause, acute renal failure (rise 1-2/d), end stage chronic renal failure (SCr > 10 mg/dL)
Non-anion gap due to base loss from GI tract (diarrhea, vilous adenoma), kidneys (renal tubular acidosis) – K low in all of these except high in type IV RTA
ACID OVERPRODUCTION
Diabetic ketoacidosis
Uremia
Methanol
Paraldehyde
Salicylates
Alcoholic ketoacidosis
Lactic acidosis
Ethylene Glycol
METABOLIC ALKALOSIS
- High HCO3-, high pH, low K+
- Most commonly due to vomiting, dehydration (urine Cl low)
- Rarely due to excess mineralocorticoids (Cushing’s, hyperaldosteronism)
RESPIRATORY ACIDOSIS
- Increased pCO2, low pH
- Due to decreased alveolar ventilation
- Usually chronic (COPD)
- Acute due to worsening of COPD, respiratory depression, pneumonia, ARDS, chest injury
RESPIRATORY ALKALOSIS
- Decreased pCO2, high pH
- Due to increased alveolar ventilation
- Usually acute, due to anxiety, pain,
- Chronic due to chronic hypoxia, stimulating respiratory center - shunting, interstitial lung disease
OXYGEN AND HEMOGLOBIN
Factors affecting pO2 include ventilation, capillary exchange, and hemoglobin binding
High oxygen affinity (left shift), less tissue delivery: low 2,3 DPG, T, pCO2, H+
Low affinity (right shift) increases oxygen delivery: high 2,3 DPG, T, pCO2, H+
Oxyhemoglobin Saturation
see image
BODY COMPARTMENTS
- Total body is ~ 60% water
- Intracellular fluid - 60% of H2O - high in K, PO4, protein
- Extracellular fluid – 40% - high in Na, Cl
- Interstitial fluid - 30% - low in protein
- Intravascular plasma - 10% - higher in protein
FLUID BALANCE
- Water lost daily; urine losses average 1.5 L, minimum about 0.5 L
- “Insensible” losses in sweat, breath about 1 L/d
- Thirst most important defense mechanism; AVP (ADH), aldosterone also important
- Natriuretic peptides only active hormones for water/Na+ loss
SERUM TESTS of Fluid and Electrolytes
- Na, K measured in serum, regulated in water phase of serum; when H2O < 93% of plasma ( protein, lipids), serum Na falsely low (indirect ISE, flame)
- Na activity (related to Na in H2O) not affected by change in plasma water (direct ISE: Vitros, whole blood)
- Osmolality (discussed earlier); BUN/creat. evaluate plasma volume (high when V , low when V )
URINE TESTS
Urine Na best evaluated by FENa; maximal reabsorption = FENa << 1%
Urine osm: maximum dilution < 100, maximum concentration > 500
HYPERNATREMIA
- Almost always due to dehydration (loss of low sodium fluid) without water replacement
- Common in those without access to water (infants, bed-bound) or with impaired thirst receptors (dementia, neurologic disorders)
- Rarely due to diabetes insipidus, hypertonic solutions
HYPONATREMIA
Usually due to one of five mechanisms:
- Pseudohyponatremia (very rare)
- Osmotic water shifts (rare)
- Na wasting (renal, extrarenal)
- Excess water (SIADH, polydipsia)
- Edematous states (cirrhosis, CHF, nephrotic syndrome)
Laboratory Findings in Hyponatremia
see pic
HYPERKALEMIA (exclude artifactual)
Must first exclude artifactual hyperkalemia:
- Hemolysis
- Delayed separation (especially if refrigerated)
- EDTA contamination
- Fist clenchinng/relaxing during draw
- Thrombocytosis (serum only)
- Lymphocytosis (plasma only)
HYPERKALEMIA
True hyperkalemia usually due to:
- Decreased excretion (renal failure, low aldosterone) most common (also type IV RTA)
- Shift of potassium out of cells (low insulin, acidosis, cell lysis)
- Increased intake
HYPOKALEMIA
True hypokalemia usually due to:
- Increased excretion (diuretics, hyperaldo, RTA, low Mg), GI losses (vomiting, diarrhea, villous adenoma)
- Decreased intake
- Shift of potassium into cells (correction of insulin deficiency, refeeding, alkalosis)
TUMOR MARKERS - General Features
Either produced by or components of tumor cells
- Used to diagnose, monitor cancer
- Ideally, specific to tumor, tissue of origin; detect tumor at early stage; levels related to stage, useful for prognosis; can follow course of disease
- Most tumor markers not ideal
Categories of Tumor Markers
- Normal cell products (PSA, Tg, IgG)
- Oncofetal antigens (CEA, AFP, HCG)
- Surface proteins (CA 19-9, 125, 15-3)
- Hormone receptors (ER/PR, EGFR, HER-2/neu)
- Genetic markers
CEA
- Family of surface glycoproteins
- Shed by cell injury, cleared by liver
- Produced by variety of cancers (GI tract, pancreas, lung, uterus, breast)
- In colon CA, increased in 25% of localized, 70-90% of metastatic
AFP
- Made by fetal hepatocytes, yolk sac (peak 2nd trimester 106 times adult levels)
- Re-expressed by hepatocyte regeneration
- When > 100x increased, fairly specific for HCC (50% sensitive), yolk sac tumor
- L3 variant more specific for HCC, associated with more aggressive tumors
PSA
- Enzyme (human kallikrein 3)
- Circulates bound to protease inhibitors; inactive (free) form higher in BPH
- Relatively specific to prostate, not Ca
- Rapid rises (> 0.75 ng/mL/yr), high values in small prostate more specific
- Should be undetectable after surgery, within ref. range after XRT
CA 15-3/27-29
- Different assays for overlapping regions of same antigen
- Originally found in breast cancer cells, also in lung, pancreas, colon, ovary
- Like CEA, also high in 25% localized, 70% advanced; also high with liver disease
CA 19-9
- Related to Le blood antigen (not made in Le negative)
- Found in pancreas, bile duct, GI tract, lung, breast CA
- In pancreatic CA, high in 40% with small tumors, 80-90% with advanced
- May be markedly increased by cholestasis/cholangitis, falls with stenting
CA-125
- Ovarian surface glycoprotein; also endometrial, pancreas, GI, lung, breast
- High in ovarian surface tumors (not mucinous), 30-40% stage I, 80-90% stage IV tumors
- Also increased by pregnancy, endometriosis, cirrhosis, ascites
ER/PR
- Found in hormonally responsive cells, not in circulation
- In breast CA, indicates better prognosis, response to estrogen deprivation, tamoxifen, aromatase inhibitors
EGFR
- Epidermal growth factor receptor (I)
- Prognostic in colon, lung, H&N, esophageal CA when overexpressed
- Antagonists available for treatment of tumors expressing receptor
- Those with mutated ras gene do not respond to antagonists
HER-2/neu
- Member of EGFR family
- Overexpression in breast Ca indicates poor prognosis; can be treated with antagonist (Herceptin)
- Gene can be detected by FISH, receptor by IHC in cells; excess protein can be detected in circulation (correlation not exact)
