Term
| how much acid does the human body generate each day? what makes up this acid? |
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Definition
| ~ 1 mEq/kg of H+ and countervailing anions (A-) |
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Term
| what is the major buffer in human blood? what is the ratio of this buffer to level of acid in the body? |
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Definition
| HCO3-, which combines with H+ to give H2CO3. H2O3 then dissociates into H20 and CO2, which is expelled by the lungs. (one bicarb lost for each proton generated) |
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Term
| what are the two main methods for the body to regenerate HCO3-? |
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Definition
| 1) the kidney can dump an anion and regenerate one bicarb molecule for each anion excreted 2) the liver can metabolize the anion back to bicarbonate if the anion cannot be renall excreted |
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Term
| how does the kidney maintain bicarb levels? |
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Definition
| first it has to *reclaim filtered bicarb in the PCT, then it has to *regenerate bicarb in the collecting duct |
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Term
| how does the kidney (indirectly) reclaim filtered bicarb in the PCT? |
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Definition
| the kidney secretes protons in the PCT via the Na+/H+ antiporter (very important molecule for reabsorbing bicarb). Na+ goes down its electrochemical gradient, which provides the energy for the PCT cells to kick out a proton which combines with a bicarb molecule (= carbonic acid) and under the influence of carbonic anhydrase becomes CO2 and H2O. the CO2 diffuses back into the cell and combines with the OH anion under the influence of intracellular carbonic anhydrase to make bicarbonate again, which can be expelled at the basolateral surface. |
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Term
| what stimulates bicarb reclamation in the PCT (via the Na+/H+ antiporter)? |
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Definition
| hypokalemia (stimulates ammoniagenesis which helps facilitate H+ secretion in CCD), AII, CO2 excess, hypercalcemia, and ECF contraction |
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Term
| what decreases bicarb reclamation in the PCT? |
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Definition
| hyperkalemia, CO2 decrease, hypocalcemia, hypophosphatemia, or ECF expansion |
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Term
| what is one of the major cells in the CCD? |
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Definition
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Term
| how does the principal cell manage Na+, K+, and Cl-? |
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Definition
| Na+ moves in from the urinary lumen into the principal cell down its concentration gradient, (due to action of basolateral 3Na+/2K+ transporter), and electric gradient (due to action of basolateral 3Na+/2K+ transporter). Cl- is reabsorbed paracellularly (between principal cells), much slower than Na+, making the luminal surface of the principal cell more negative (this allows K+ to be secreted) |
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Term
| what is the function of the intercalated cells in the CCD? |
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Definition
| the intercalated cell is responsible for secreting protons, which is done via an ATPase. when H+ is secreted (taken from water), OH- is left behind - which carbonic anhydrase combines w/CO2 to make HCO3-. the luminal space is negative (due to the action of the principal cell), which also facilitates H+ secretion |
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Term
| what happens if the intercalated cells secrete enough H+ that the pH drops to a point where the luminal surface is no longer negative? what is the hormone that drives this process? |
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Definition
| ammonia (NH3-) that is generated in the PCT makes its way to the CCD and combines with H+ to make NH4+ (ammonium), bringing the urinary pH back up (facilitates further secretion of protons). NH4+ then combines with Cl- and is dumped in the urine. *the hormone that drives this process is aldosterone.* |
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Term
| how does aldosterone drive the process of Na+ reabsorption, proton secretion, bicarb reformation/reclamation? |
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Definition
| aldosterone leads to increased H+/K+ pumps on the basolateral surface and increased Na+ channels on the luminal surface (increases luminal electronegativity) |
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Term
| what is metabolic acidosis due to? |
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Definition
| *increased generation of H+ (can be non-anion gap if countervailing anion excreted in urine, but if retained, this leads to anion gap metabolic acidosis) or *loss of bicarbonate (usually non-anion gap) |
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Term
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Definition
| the anion gap is the Na+ minus Cl- minus bicarbonate. this represents anions not measured in the basic metabolic panel and is *usually 10-12 mEq/L*. (Na - Cl - HCO3 = anion gap, where Cl- and HCO3 represent the "measured" anions). in normal health there are more unmeasured anions(compared to unmeasured cations) in the serum; therefore, *the anion gap is usually positive*. |
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Term
| what is one of the major unmeasured anions (that can contribute to the anion gap)? what happens the level of this molecule does down? are there other molecules/conditions that commonly cause an anion gap decrease? |
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Definition
| albumin (usually 4-4.5 g/L), which if this goes down b/c the pt is malnourished, will *cause the anion gap to decrease (for each decrease in albumin of 1, the anion gap drops by 2.5). increased globulins (IgG, etc are cationic - seen w/myeloma in a monoclonal spike) can also decrease the anion gap. |
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Term
| what will cause the anion gap to increase? |
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Definition
| the anion gap will increase due to an increase in unmeasured anions (such as in certain metabolic acidosis) or due to a decrease in unmeasured cations (such as severe hypocalcemia -> very rare) |
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Term
| what is metabolic acidosis usually reflected by? |
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Definition
| low bicarb and low blood pH |
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Term
| how do the lungs compensate for metabolic acidosis? |
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Definition
| by blowing off increased levels of CO2, which tends to return the pH to normal. (pH = 6.1(log to base 10) + bicarb/.03 x pCO2) |
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Term
| what is the purpose of winter's formula? what is the formula? (*exam question*) |
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Definition
| winters formula allows you to calculate what the pCO2 should be for any given drop in bicarb due to a metabolic acidosis. pCO2 = bicarb x 1.5 + 8 +/-2 |
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Term
| what does it mean if the pCO2 is higher than that predicted by winter's formula? |
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Definition
| if the pCO2 is higher than predicted by winter's formula, the pt has a primary respiratory acidosis (can happen w/emphysema - pt can't blow off enough CO2) |
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Term
| what does it mean if the pCO2 is lower than that predicted by winter's formula? |
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Definition
| if the pCO2 is lower than predicted by winter's formula, the pt has a primary respiratory alkalosis (can happen with septic pts or ASA OD) |
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Term
| what does it mean if the pCO2 is the same as that predicted by winter's formula? |
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Definition
| the pt has appropriate respiratory compensation for a bicarb drop due to metabolic acidosis |
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Term
| what is the most common type of metabolic acidosis seen in the hospital? |
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Definition
| anion gap metabolic acidosis, which is usually due to *increased generation of organic acids w/retention of countervailing anions. *L-lactic acidosis is the most common; due either to an *increased lactic acid generation or *decreased metabolism. (increased generation usually due to decreased O2 delivery to tissues w/conversion to anaerobic metabolism, *such as in shock* - type A) |
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Term
| other than septic shock, what are other possible causes of L-lactic acidosis (type B)? |
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Definition
| increased L-lactic acid production: malignancies, AIDS, and pheochromocytoma. decreased metabolism: advanced liver disease (cirrhosis) |
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Term
| what are other causes of anion gap metabolic acidosis besides L-lactic acidosis? |
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Definition
| methanol, ethylene glycol, *DKA* (diabetic ketoacidosis - second most common after L-lactic acidosis), AKA, starvation ketosis, uremia, and ASA OD (usually accompanied by respiratory alkalosis) |
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Term
| what is the most common cause of non-anion gap metabolic acidosis? |
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Definition
| bicarb loss, either renally (such as w/RTA: renal tubular acidosis - failure of the kidneys to appropriately acidify the urine) or extrarenally (diarrhea) |
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Term
| what are other causes of a non-anion gap metabolic acidosis besides bicarb loss? |
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Definition
| non-anion gap metabolic acidosis is usually due to an increased generation of acid, where the countervailing anion is renally excreted w/the retention of Cl-. examples of this are D-lactic acidosis (short bowel syndrome, bacterial overgrowth = D-lactate production, which is then renally excreted), glue sniffing (creates hippuric acid (countervailing anion), which is renally excreted and the kidneys hold onto Cl to maintain electroneutrality = no change in anion gap), TPN (direct addition of HCL to bloodstream) |
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Term
| how are renal and extrarenal etiologies (RTA vs diarrhea) for non-anion gap metabolic acidosis differentiated? |
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Definition
| via the *urine gap, which is = urine Na plus K minus Cl. extrarenal acidosis is accompanied by increased renal ammoniagenesis, which allows the kidney to secrete more protons to compensate ammonia which is then protonated to ammonium which obligates urinary loss of Cl (via NH4Cl). *this will cause the urine anion gap to become negative* with RTA, the kidney can't dump Cl-, and the urine anion gap will become positive. |
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Term
| how are the 4 major types of RTA distinguished? |
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Definition
| measurement of serum K+ and urine pH |
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Term
| what is the most important type of RTA? (*don't need to know for exam) |
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Definition
| type IV RTA or hyporenin hypoaldo. this is characterized by *hyperkalemia with a urine pH less than 5.3. these pts have low renin level, and thus a defective RAS, no aldosterone = hyperkalemia - which shuts off ammoniagenesis, which lowers bicarb (can't trap protons in the CCD - see earlier question: what decreases bicarb reclamation in the PCT?) |
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Term
| what kinds of pts often get type IV RTA or hyporenin hypoaldo? (*don't need to know for exam) |
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Definition
| diabetics, obstructed uropathies, elderly (usually lower renin levels) |
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Term
| what is type II RTA? (*don't need to know for exam) |
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Definition
| proximal RTA is due to a defect in bicarb reclamation |
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Term
| what is type I RTA? (*don't need to know for exam) |
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Definition
| classic distal RTA is usually due to sjogren's syndrome and amphotericin and is caused by a defect in the proton pump |
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Term
| what is hyperkalemic distal RTA? (*don't need to know for exam) |
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Definition
| this is usually due to a defect in aldosterone release or resistance due to aldosterone (due to CCD damage). common etiologies: sickle cell anemia, obstructive uropathy, interstitial nephritis |
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Term
| what is metabolic alkalosis characterized by? what is it usually due to? |
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Definition
| high bicarb and high blood pH. metabolic alkalosis is usually due to *gain or generation of bicarb (usually leads to volume expansion/HTN) OR *loss of HCL (usually leads to normotension, hypotension, or volume depletion) |
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Term
| how do determine if a metabolic alkalosis due to HCL loss is renal or extrarenal? |
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Definition
| measurement of urine Cl. urine Cl >25 mEq/L implies renal HCl loss (diuretics and bartter's syndrome). urine Cl <25 mEq/L implies extrarenal losses of HCl (vomiting) |
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Term
| what do you do if you have a pt w/a metabolic alkalosis who is not volume depleted but is hypertensive? |
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Definition
| measure renin and aldosterone - have to suspect there is a primary problem with the RAS. |
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Term
| how do you determine *appropriate resp compensation for metabolic alkalosis? |
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Definition
| there is an increase of 0.7 mm Hg in pCO2 for each increase of 1 in bicarb |
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Term
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Definition
| the delta/delta is the ratio of change in bicarb over change in anion gap and allows one to determine if there are 2 simultaneous metabolic processes occurring at the same time. |
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Term
| how is the delta/delta applied? |
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Definition
| if the ratio is > 1: there is a simultaneous metabolic alkalosis and anion gap metabolic acidosis. (ex: if a pt's anion gap increases, their bicarb should decrease in a 1:1 ratio, but if the bicarb doesn't decrease, the pt would then have a metabolic alkalosis in addition to a metabolic anion gap acidosis. vomiting DM pts w/ketoacidosis will present this way.) if the ratio is < 1: there is a presence of non-anion gap and anion gap acidosis. (ex: pt with a bicarb of 10 and anion gap of 20, such as a pt w/severe diarrhea due to ischemic colitis: shock (lactic acidosis)) |
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Term
| what does the osmolar gap help you determine? |
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Definition
| this can help you determine if a pt has taken in a poison or toxin (often methanol or ethylene glycol) |
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Term
| how is the osmolar gap determined? |
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Definition
| the calculated serum osm (Na x2 + glucose/18 + BUN/2.8) is subtracted from the mesured serum osm. normally this difference is <10, but if higher you can suspect poisoning (ethanol, methanol, ethylene glycol, ASA and isopropanol - usually only methanol/ethylene glycol increase the anion gap and give metabolic acidosis) |
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Term
| what is respiratory alkalosis characterized by? what might cause this? how long does metabolic compensation take and is there an acute/chronic difference? |
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Definition
| respiratory alkalosis is usually characterized by low pCO2 and high blood pH and usually due to sepsis, cirrhosis, ASA, CHF or pneumonia. metabolic compensation takes about *48 hrs. *acutely there is a drop of 2 bicarb for each 10 mm Hg drop in pCO2, chronically there is a drop of 5 bicarb for each 10 mm Hg drop in pCO2. |
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Term
| what is respiratory acidosis characterized by? what might cause this? how long does metabolic compensation take and is there an acute/chronic difference? |
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Definition
| respiratory acidosis is usually characterized by a high pCO2 and low blood pH and is commonly caused by COPD, narcotic OD, and neuromuscular disease. metabolic compensation by the kidneys takes *72 hrs. *acutely: there is an increase of 1 bicarb for each increase of 10 pCO2, chronically there is an increase of 3.5 bicarb for 10 PCO2. |
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Term
| what is a common combination of findings? what is the ddx? (*prob exam question*) |
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Definition
| anion gap metabolic acidosis and respiratory alkalosis, for which the ddx is *ASA OD, sepsis (most common), and advanced liver disease (cirrhosis) |
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Term
| how are acid/bast disturbances usually recognized on routine chemistries? what would need to be done for a full evaluation? |
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Definition
| thee is usually an increase in the anion gap or an abnormal bicarbonate level. a full evaluation would require an ABG. |
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Term
| what are urine lytes useful for? |
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Definition
| evaluating metabolic alkalosis and nonAG metabolic acidosis |
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Term
| what are urine pH and serum potassium helpful for evaluating? |
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Definition
| non AG metabolic acidosis due to RTA |
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Term
| what are osmolar gaps helpful for? |
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Definition
| anion gap metabolic acidosis |
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Term
| what needs to be calculated whenever there is an anion gap? |
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Definition
| the delta/delta, *which needs to always be corrected for serum albumin. |
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Term
| what is helpful to measure in pts w/HTN and metabolic alkalosis? |
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Definition
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