Lecture 16: Metabolic Acidosis Flashcards

Question

How does hyperkalemia fuck up ammoniagenesis?

Answer 1

Since K travels from ECF to ICF, it will then mean the cell’s H+ will have to go from ICF out to ECF in order to counteract K influx Thus K influx = increased pH Increased pH = impairment of enzymes involved in ammoniagenesis (which takes a glutamine and breaks that shit down twice to alphaketoglutarate)

Answer 2

Caused by decreased capacity of proximal tubule to reabsorb HCO3 Result = increase in fractional excretion of HCO3 Decreases threshold at which HCO3 reabsorption plateaus Normally, there is a threshold at which HCO3 reabsorption can no longer increase, despite the plasma HCO3…however normally, this threshold is 25 HCO3 mEq/L…in proximal PTA, the threshold is 19 HCO3 mEq/L…this means less bicarb is reabsorbed Urine pH is LOW for proximal RTA patients since the ability to acidify urine is determined by distal nephron -is high at first but will eventually be low pH at steady state

Answer 3

Urine will have so much bicarb, that distal tubule is unable to reabsorb it and the pH will actually start out high However, since there is less bicarb reabsorption at this point, there will be less bicarb volume filtered over time (which is case C in the figure), thus there will be less bicarb in the urine and closer to the threshold In case B, body reaches a steady state, and only enough bicarb is secreted such that all of it can be reabsorbed in the distal tubule and the urine pH remains acidic (5.5) -if you notice in case B, bicarb filtration is 15 mmole/L vs 26 mmole/L of normal patient

Answer 4

Giving acetazolamide (carbonic acid anhydrase inhibitor) Carbonic anhydrase II genetic mutation Mutation in Na/HCO3 cotransporter gene (isolated proximal RTA) Fanconi Syndrome

Answer 5

``` Disease of proximal renal tubules When glucose, amino acids, uric acid, phosphate and bicarb are passed into urine instead of being reabsorbed Caused by a shitload of things such as i. tetracycline ii. tenofovir iii. lead poisoning iv. cystinosis v. Wilson disease vi. Lowe’s syndrome vii. hereditary fructose intolerance viii. multiple myeloma etc. (more causes listed on slide 15) Cystinosis is most common cause in children Multiple myeloma is common in adults of no drugs are present ```

Answer 6

A lysosomal storage disease characterized by abnormal accumulation of amino acid cysteine Can effect the transporters in proximal renal tubule thereby impairing reabsorption Most common cause of Fanconi syndrome in children

Answer 7

Proximal RTA = low pH of URINE after steady state is reached Distal RTA = high pH of URINE -this is because if distal nephron is fucked, one cannot acidify urine well

Answer 8

1. H+ ATPase | 2. Na/H apical channel

Answer 9

Carbonic acid is broken down by carbonic anhydrase leads to H2O and CO2, which diffuse into the cell and leave cell to bloodstream as bicarb (in Na/bicarb symporter)

Answer 10

In contrast with RTA, the problem is with H+ secretion and excretion in the distal nephron Impairment of acidification of final urine Reabsorption of distal RTA thus has the same or higher reabsorption threshold than normal Thus there is no defect in bicarb reabsorption Classic feature of distal RTA: no matter what the serum bicarb, you have high urine pH (because not able to secrete H+)

Answer 11

1. Defect in apical H+/ATPase 2. defect in apical H/K ATPase - rare - due to toxins/contaminants like vanadium 3. H+ backleak - caused by amphotericin - drugs that disrupt membrane integrity 4. Carbonic anhydrase II deficiency - genetic, associated with proximal RTA 5. defect in basolateral Cl/HCO3 cotransporter

Answer 12

Most common defect in pump present in alpha intercalated cells Acquired and genetic Genetic = growth defects and kidney stone Associations Acquired = associations with Sjogrens

Answer 13

Variable K concentration but usually a bit low

Answer 14

Mild hyperaldosteronism due to loss of Na w/ HCO3 and NaCl (due to acidosis) causing mild hypovolemia Increased distal nephron delivery of Na and bicarb stimulates K secretion Defect in H/K ATPase reducing K reabsorption (distal RTA) Increased membrane K permeability (amphotericin B, distal RTA)

Answer 15

Bicarb will just be excreted in the urine and won’t be reabsorbed In a distal RTA, extra bicarb will be reabsorbed and more effective of a treatment

Answer 16

The total acid burden with distal RTA is much greater because there is no factor to diminish bicarb excretion Proximal RTA can adjust its bicarb excretion, since it has normally functioning distal components

Answer 17

Proximal RTA = higher doses of sodium bicarb in order to maintain normal levels of serum bicarb since there will be a high rate of urinary loss Distal RTA = LOWER doses of sodium bicarb since most of it gets reabsorbed by the functioning proximal tubule

Answer 18

Type IV RTA Hyperkalemia and metabolic acidosis is caused by Type IV RTA Hyperkalemia and metabolic acidosis is caused by hypoaldosteronism

Answer 19

Because hyperkalemia reduces ammoniagenesis, reabsorption of ammonium in TAL, and secretion of ammonium in collecting ducts

Answer 20

1. Mineralocorticoid deficiency Primary due to adrenal insufficiency, inherited disorders or drugs Hyporeninemic hypoaldosteronism -diabetes, tubulointerstitial kidney diseases, NSAIDs 2. Mineralocorticoid resistance Due to PHA-1 (pseudohypoaldosteronism type I) -autosomal dominant mineralocorticoid receptor defect 3. Distal nephron tubular dysfunction 4. PHA-2

Answer 21

1. heparin (inhibits aldosterone synthesis) 2. Angiotensin II inhibitors 3. NSAIDs 4. amiloride, trimethroprim, triamterene 5. cyclosporine and tacrolimus (interfere with Na/K ATPase) 6. spironolactone and eplerenone

Answer 22

Pseudohypoaldosteronism type 2 Aka Gordon’s Syndrome or Familial Hyperkalemic HTN Due to mutations in genes that encode kinases, resulting in uncontrolled activation of Na/Cl symporters in DCT -increase Na reabsorption = downregulation of aldosterone = hyperkalemia and metabolic acidosis

Answer 23

Can cause respiratory alkalosis because aspirin stimulates hyperventilation Can cause metabolic acidosis because it can uncouple oxidative phosphorylation Anion gap alteration due to salicylate anion, ketosis (altered glucose metabolism and hypoglycemia) as well as L-lactic acid production

Answer 24

Ketoacidosis Lactic acidosis Increases anion gap

Answer 25

1. methanol 2. ethylene glycol 3. diethylene glycol 4. Toluene 5. Aspirin

Answer 26

Occurs when lactate > 5mM H-pyruvate + NaDH + H H-lactate + NAD+ Pyruvate is product of glycogen, glucose and alanine MET -lactic acid levels reflect NADH/NAD ratio Has two types: i. Type A ii. Type B Also there are two types of lactic acid L-lactic acid = product of metabolism D-lactic acid = product of bacterial metabolism (due to short bowel syndrome or bowel obstruction)

Answer 27

Most common type of lactic acidosis | Caused by hypoxia, sepsis, severe anemia, CO poisoning, hypotension

Answer 28

Due to compromised metabolism of lactate in the absence of overt hypoxia leading to excess production of lactate and/or decreased conversion back to pyruvate Caused by liver disease, thiamine deficiency, alcohol ingestion, mitochondrial toxins, malignancy (tumor lysis syndrome), seizures, inborn errors of metabolism Also caused by drugs like metformin and nucleoside reverse transcriptase inhibitors

Answer 29

Occurs in absence of insulin Also occurs in starvation and alcoholics Can be caused by release of catecholamines as well (makes sense since cortisol inhibits insulin effects) Absence of insulin = unregulated metabolism of FFA = acetyl CoA = acetoacetic acid + beta (OH) butyric acid

Answer 30

Insulin deficiency = promotion of lipolysis (stimulation of lipase) Increases FFA delivery to liver

Answer 31

Beta-hydroxy butyrate Ethanol is metabolized to acetaldehyde and acetic acid by alcohol DH CYP450 pathway in fetuses (when enzymes are yet to be produced)

Answer 32

If the breakdown products of the toxins are acidic Formic acid from methanol Oxalic acid from ethylene glycol for instance (see above)

Answer 33

Give them ethanol! Since ethanol binds to alcohol dehydrogenase (the enzyme that breaks down all three molecules) with 100x more affinity than other 2 Fomepizole, an ADH inhibitor is also commonly used

Answer 34

Measured by Posm = 2Na + BUN/2.8 + glucose/18 | Normally the measured Posm > calculated Posm by 5-10 mosm/L

Answer 35

Indicates likely presence of an osmotically active particle present in the blood but is not part of equation shown above Example: ethanol Ethanol intoxication is MOST COMMON increased osmolar gap Can also be caused by methanol and methylene glycol

Answer 36

Early on, osmolar gap > anion gap for methanol intoxication Later on, Anion gap > osmolar gap for methanol intoxication Anion gap = breakdown products being effective osmoles Occurs because methanol gets metabolized

Answer 37

Refers to the phenomenon in which anion gap increases the SAME amount that bicarb falls in response to simple organic acidosis

Answer 38

Refers to the change in anion gap

Answer 39

May be a clue that there is more than one acid-base disturbance So if change of anion gap does NOT match change of bicarb, then it signifies the presence of a mixed process Theory is that for every acid added, it is buffered by one bicarb so serum bicarb should fall in paralle with increased anion gap

Answer 40

1. hyperventilation -kussmaul respiration -respiratory compensation 2. Hemodynamic compromise (vasodilatation) -blood vessels cant retain tone 3. Hyperkalemia 4. Musculoskeletal manifestations (chronic) Acute acidosis is harmful because of underlying cause Chronic acidosis can lead to impaired growth and muscle development in children -chronic acidosis can also cause osteopenia due to bone buffering and muscle catabolism -release of calcium from bone = hypercalcuria, kidney stones

Answer 41

1. lung | 2. kidneys

Answer 42

A process that corrects for primary defect Example: lowered pH from metabolic acidosis can lead to lowering the pCO2 in lungs Or kidneys can increase/decrease bicarb generation to account for respiratory acid-base disturbance

Answer 43

1. It is NOT second disorder 2. never perfect 3. no such thing as overcompensation - if there is overcompensation, then that signifies a possible second primary process going on Metabolic acidosis = hyperventilation = decrease pCO2 Metabolic alkalosis = hypoventilation = increased pCO2 Respiratory acidosis = increased plasma bicarb reabsorption and increased H/K reabsorption) Respiratory alkalosis = decrease plasma bicarb and decrease renal H and becarb reabsorption)

Answer 44

Winter’s formula | Expected pCO2 = 1.5 * bicarb + 8 (within +/- 2)

Answer 45

There must be an additional acid-base disorder (respiratory alkalosis additionally) Superimposed hyperventilation

Answer 46

No such thing as overcompensation | There must be an additional acid-base disorder (respiratory acidosis perhaps)

Answer 47

Increased glutamine uptake by PT cells, muscle release of glutamine and metabolism of glutamine Can be due to upregulation of N/H exchanger, H-ATPase, H-K ATPase

Answer 48

The patient had a second acid-base disorder called respiratory alkalosis

Answer 49

1. Treat underlying cause 2. oral or IV NaHCO3 or an equivalent such as citrate -desired delta bicarb * 50% body weight in kg = amount of sodium bicarb given Chronic therapy = use bicarb to stabilize pH Acute therapy = not necessary to normalize pH or bicarb…focus is on keeping blood pH above 7.2 through respiratory or bicarb treatment Underlying process > pH in terms of importance

Answer 50

1. hypernatremia and volume overload 2. hyperkalemia (if given as hypertonic bolus) 3. CO2 generation 4. CSF acidosis due to CO2 diffusion across blood brain barrier 5. Overshoot alkalosis - as organic acid gets metabolized (lactic acid and ketoacidosis) 6. Hyperventilation will also raise pH

Answer 51

Occurs when you administer sodium bicarb in patients with lactic acidosis or ketoacidosis Patient metabolizes lactate/ketones and generates bicarbs endogenously Bicarb is also added exogenously (as treatment) Thus endogenous vs exogenous bicarb = alkalemia