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34 Cards in this Set

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  • Back
Describe acid balance in a normal individual
-50-100mEq acid production through normal oxidative processes
-Concentration of hydrogen in body fluids is 40nmol/liter
-50-100mEq excreted in urine
-Only 10uEq is H ion
-Most of it is ammonium
What is the most important buffer in the body?
Bicarbonate
Describe bicarbonate as a buffer
-Important because it can be regenerated and can dissociate
-When we add acid to the body the kidney is supposed to cause a reaction that produced CO2 which is easily breathed out
-We are left with a deficit of bicarbonate
-This deficit is replaced with bicarbonate from the kidney
What is the Henderson Hasselbalch equation
pH=pK+log([HCO3]/alphapCO2)

pK=6.1
alpha=0.03
Describe how the kidney produces bicarbonate
-Apical membrane of epithelial cells has a hydrogen ion pump
-It takes water and splits it into hydrogen and hydroxl
-Hydrogen ion is transported into the urine
-Remaining hydroxl is carboxylated through carbonic anhydrase to produce bicarbonate
-Bicarbonate is added to the body fluid
Describe the role of the kidney with respect to bicarbonate
-Kidney can make new bicarbonate and add it to body bluids to balance against acid from diet
-Kidney filters blood full of bicarbonate
-Kidney has to reabsorb this bicarbonate
-Reabsorbed bicarbonate is quantitatively much more significant
Describe how bicarbonate is reabsorbed
-Same hydrogen ion secretion used to make bicarbonate is used to reabsorb filtered bicarbonate
-Urine contains filtered bicarbonate and hydrogen ions are pumped into urine
-Bicarbonate + Hydrogen makes CO2 and water
-The CO2 is permeable and enters the cell
-CO2 reacts with OH to make bicarbonate
Where in the kidney does HCO3 reabsorption/H secretion occur?
Proximal and collecting tubule
Describe H secretion in the proximal tubule
-There is a Na-H exchanger, absorb Na and secrete H
-Use energy from the low Na in cell and high Na in urine
-There is also a proton translocating ATPase in hte lumenal membrane
-Bicarbonate produces is translocated across the basolateral membrane by a Na:HCO3 cotransporter
-With this process we can reabsorb >90% of filtered bicarbonate
-The rest reaches the collecting duct and is reabsorbed there
-NHE3= Na:H exchanger
-NBC Na:HCO3 cotransporter
Describe the location of ion transports/channels in proximal tubule cells
-NaK ATPase is present in the basal and lateral membranes
-NaH exchanger is present only in the lumenal membrane
-NBC1 (Na:HCO3) is also present in the basal and lateral membranes
Describe the cell types in the collecting tubule
-Principal
Na+ absorption ENaC
Water absorption Aquaporin 2
K+ secretion ROMK
-Intercalated
H+ Transport H+ ATPase
Describe H secretion in the collecting tubule
-There is only a hydrogen ATPase on the apical membrane
-There is a Cl-bicarbonate (AE1) exchanger present on the basolateral side
Describe the regulation of H+ transport
-Heavily regulated process
-pCO2 and aldosterone each induce an increase in H ion secretion
-K, Acid-Base status, NH3, pH gradient, membrane potential
Describe the effect of CO2 on hydrogen secretion
-CO2 stimulates function of hydrogen vesicles
-CO2 enters cells, lowering pH
-Low pH causes release of Ca which causes vesicle fusion
-Occurs mainly in the collecting duct, but some in te proximal tubule
Describe what happens to bicarbonate and hydrogen with hyperventilation
-pCO2 drops
-Initially bicarbonate drops (low CO2 forces low pCO2)
-Initial acute response is followed by further drop
-Drop is because we dont reabsorb the filtered bicarbonate
-When you reduce pCO2 suddenly the H ion concentration in the blood drops to low levels
-As you lose bicarbonate the H ion concentration returns towards normal
Describe what happens to bicarbonate and hydrogen with hypoventilation
-Very high pCO2
-Sudden increase in the bicarbonate but slowly you find more and more bicarbonate in the blood
-Kidney is stimulating secretion of hydrogen ions and making new bicarbonate and every day adding it to the body fluids
Describe how membrane potential affects H secretion
-You can stimulate hydrogen ion secretion by negative membrane potential
-You can inhibit hydrogen ion secretion by a positive membrane potential
Describe how aldosterone affects H secretion
Aldosterone stimulates hydrogen ion secretion directly, independent of the membrane potential
Describe how the membrane potential is affected by Na reabsorption
-Na absorption regulates H and K secretion in the collecting tubules
-When you absorb Na you make the lumen negative
-That forces more H and K ions out
-If you give a patient diuretics the collecting tubule is flooded with sodium
-More sodium is absorbed, so the membrane potential becomes negative and lots of H and K are secreted
-Patients with high aldosterone receive diuretics
Describe the generation of the ammonium in urine
-Epithelial cells produce ammonia
-Ammonia goes into the urine and traps hydrogen
-We can excrete 40-50 mEq of ammonia daily
-Ammonia comes from gluconeogenesis
-Glutamine is converted to glucose by glutaminase 1 and 2, each step releasing 1 NH3 molecule
-This only happens in the kidney
-Acidosis stimulates glutaminase acivity
Describe the effect of acid ingestion on ammonia synthesis
-As mEq is ingested, ammonia production i sstimulated almost immediately and reaches steady state in a few days
-Ammonia production maxes out around 250 mEq
-The kidney is able to defend the pH of body fluids
-Each nephron in the kidney is able to increase the ammonia production in response to acidosis by 4-5x
When do people with renal failure become acidotic?
When take away 3/4 of the kidney tubules
Describe tubular interstitial diseases
-The GFR is preserved
-Interstitium has inflammation and this destroys some of the tubules, causing tubular atrophy
-Some tubules can not generate enough ammonia
Describe how to distinguish glomerular diseases from tubular interstitial diseases
-If you see someone with a creatinine of 2-3 and they have acidosis you know it is tubular interstitial disease
-If the tubules worked then there would be no acidosis at a creatinine of just 2-3
-They could secrete NH3 if the tubules worked
-When the number of functioning nephrons falled below 20% (Cr=4) then the daily NH3 production falls below what is needed to maintain acid-base balance
Define acidosis
Blood pH<7.4
Define alkalosis
Blood pH>7.4
Describe how to differentiate between metabolic and respiratory acidosis
If the pH is low either the bicarbonate is down or the pCO2 is up. If the pCO2 has gone up it is respiratory acidosis. If the bicarbonate has gone down it is metabolic acidosis.
Describe how to differentiate between metabolic and respiratory alkalosis
If the pH is high then it is alkalosis. If the bicarbonate is high it is metabolic alkalosis and if the pCO2 is low then it is respiratory alkalosis.
Describe metabolic acidosis
-The brain senses acidosis and forces the lungs to breath fast
-Causes low pH, low HCO3, and low pCO2
-Caused by increased metabolic acid production
-Ketoacidosis from diabetes
-Lactic acid from ischemia
-HCO3 losses
-Diarrhea (colon secretes high levels of bicarbonate)
-Renal tubular acidosis
-Renal failure
-Acid ingestion
What are the main causes of metabolic acidosis?
-Increased metabolic acid production
-HCO3 losses
Describe anion gap
-Anion gap=Na-(Cl+HCO3)
-The missing anion is normally albumin and is usually ~10
-If the anion gap is high, it means there is another ion
-This is likely a metabolic acid
-Consider lactic acidosis, diabetic ketoacidosis, renal failure, and others
-A normal anion game occurs when you lose bicarbonate such as in diarrhea or renal tubular acidosis
Describe metabolic alkalosis
-Plasma bicarbonate is increased
-There is high pH, high HCO3, high pCO2
Describe the development of metabolic alkalosis
-Generation of excess HCO3
-HCO3 ingestion or acid lost
-Acid can be lost through vomiting
-Stomach produces secretes acid into stomach and bicarbonate into blood, but acid is reabsorbed in intestines
-Maintenance of Excess HCO3
-Kidney is good at excreteing bicarbonate
-Increased renal H secretion, but can max out
-Maintenance generally through volume depletion
Describe the maintenance of metabolic acidosis
-Generally through volume depletion
-Volume depletion associated with high angiotensin
-High angiotensin increases filtration fraction and reabsorption in the proximal tubule
-AII stimulates Na:H exchanger
-There is increased reabsorption of everything (Na, Cl, bicarbonate)
-Angiotensin causes high aldosterone state and aldosterone stimulates H secretion in the collecting duct
-Creates more bicarbonate and adds it to body fluids