Anion Gap Other Than Metabolic Acidosis

Conventionally Serum Anion Gap is calculated as: 

                                                                  Serum AG  =  Na - (Cl + HCO3)

•            Na  is Primary Cation
•            CL+HCO3 are Primary Anion

Serum AG  =  All unmeasured anions – all unmeasured cations

What are Unmeasure Anions?

• Any ion in the serum other than Na, Cl, or HCO3

Causes of lower Serum AG

•Hypoalbumin

•Hyperkalemia

•Hypercalcemia

•Hypermagnesemia

•Lithium toxicity

•IgG multiple myeloma

Negative Serum AG:

•      Rarely seen.
•      Laboratory error ( this is not reproducible)
•      Overestimation of serum chloride:  marked hyperlipidemia, salicylate intoxication, bromide intoxication ( in past bromide used as sedative

Case discussion

A 41 year old male presents to the ER with the following lab results (hint: look for multiple simultaneous problems).

Na 140 mmol/L
K 4.0 mmol/L
Cl 110 mmol/L
pH 7.0
pCO2 35 mmHg
pO2 75 mmHg
HCO3 8 mmol/L

Answer:

The primary disturbance in this patient is an acidosis, as indicated by the acidemic pH in the blood (pH 7.0). The normal bicarbonate concentration is 24 mmol/L but this patient’s bicarbonate concentration is 8 mmol/L. This indicates a fall in bicarbonate of 16 mmol/L.

Thus, there is a primary metabolic acidosis.

The anion gap is 22.

Recall, anion gap is calculated by the formula:

AG = Na – HCO3 – Cl

AG = 140 – 8 – 110

AG = 22

The normal anion gap is about 12, so the anion gap is increased.

Thus, there is an anion gap metabolic acidosis.

The anion gap is increased by 10 but the bicarbonate has fallen by 16mmol/L. Therefore, there is also a fall in bicarbonate that is not accounted for by the H+ ions that accompanied the unmeasured anions in this case – this means there is also a non-anion gap metabolic acidosis.

The bicarbonate has decreased by 16.

We would expect that in a metabolic acidosis, there would be a 1 mmHg fall in pCO2 for every 1 mmol/L of bicarbonate.

Therefore, we would expect that the pCO2 would be 24 mmHg. Since it is 35mmHg, it is too high and this represents arespiratory acidosis.

Therefore, this is a case of a

1. Anion gap metabolic acidosis
2. Non-anion gap metabolic acidosis

1. Respiratory acidosis

Nephrolog

List 6 clinical features of preeclampsia.

Answer
Preeclampsia usually begins in the third trimester, but can occur earlier in patients with preexisting renal disease or hypertension.  It can also occur postpartum with hypertension and seizures 24-48 hours after delivery. It usually resolves 10 days after delivery.

It presents with weight gain and edema, particularly of the hands and face, with variable increases in blood pressure and proteinuria.

There is a fall in renal blood flow and GFR that can lead to hyperuricemia and hypocalciuria as well as acute renal failure.  The acute renal failure is thought to be due to glomerular endotheliosis with swelling of endothelial cells and subendothelial hyaline and fibrin deposition.  Acute tubular necrosis and cortical necrosis can also occur.

Pulmonary edema can occur due to changes in pulmonary capillary permeability.  Hyperreflexia reflects increased nervous system excitability.When preeclampsia is more severe, it can progress to the HELLP syndrome with hemolysis, elevated liver enzymes, and low platelets.

Due to decreased placental perfusion, fetal growth restriction and oligohydramnios can occur. 

Question 37
List 4 classes of drugs that decrease cyclosporine levels and 4 classes of drugs that increase cyclosporine levels.   

Answer
Cyclosporine is metabolized by the  hepatic cytochrome P450 family of enzymes and excreted into the bile.  As a result of this, a variety of important drug interactions with drugs that either effect or are metabolized by these enzymes can occur.

Drugs that induce CYP3A4 may decrease the levels of cyclosporine.  Examples of these include carbamazepine, nafcillin, nevirapine, phenobarbital, and phenytoin.

Drugs that inhibit CYP3A4 may increase the levels of cyclosporine.  Examples of these includeazole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, isoniazid, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Cyclosporine may increase the levels of CVP3A4 substrates.  Examples of substrates include benzodiazepines, calcium channel blockers, mirtazapine, sildenafil, tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam),  and selected HMG-CoA reductase inhibitors (lovastatin and simvastatin) are generally contraindicated with strong CYP3A4 inhibitors.  

Question 38
A 67 year old female is admitted with congestive heart failure and angina.  She is started on diuretics and an ACE inhibitor and then undergoes cardiac catheterization.  Her creatinine on admission was 150 and rose to 400 three days later. 

List five potential causes for the decline in her renal function.

Answer
Possible diagnoses include:

Congestive heart failure with decreased cardiac output/Overly aggressive diuresis
Use of an ACE inhibitor in the setting of unrecognized bilateral renal artery stenosis.
Contrast nephropathy
Cholesterol embolic disease
Acute interstitial nephritis from drugs  

Question 39
Unfortunately a 37 year old male construction worker suffered severe musculoskeletal injuries after a crane had fallen on him. 

Outline the principals of management to lower his risk of rhabdomyolysis.

Answer
Rhabdomyolysis is the breakdown of myocytes with leakage of potentially toxic cellular contents into the systemic circulation.

The clinical sequelae of rhabdomyolysis include the following:

Acute renal failure (nephrotoxic effect of myoglobin)
Hypovolemia (third-spacing into injured myocytes)
Hyperkalemia (due to myocyte degeneration)
Metabolic acidosis (release of cellular phosphate and sulfate)
Disseminated intravascular coagulation (DIC)

The general recommendations for the treatment of rhabdomyolysis includes fluid resuscitation and prevention of end-organ complications:

Administer isotonic crystalloid 500 mL/h and titrate to maintain a urine output of 200-300 mL/h.  Consider invasive monitoring to assess volume status, if indicated.

Acute renal failure develops in 30-40% of patients with rhabdomyolysis. To prevent renal failure, many authorities advocate urine alkalinization (titrated to urine pH higher than 7), mannitol, and loop diuretics.

After establishing an adequate intravascular volume, mannitol may be administered to enhance renal perfusion

Loop diuretics may be used to enhance urinary output in oliguric patients, despite adequate intravascular volume.

Monitor for the development of compartment syndrome, which would necessitate a consultation for fasciotomy.

Patients with rhabdomyolysis should be supported with renal replacement therapy as indicated.

How kidney patients are presented

Abnormal laboratory studies (e.g., elevated blood urea nitrogen [BUN] and serum
creatinine, decreased estimated glomerular filtration rate, or abnormal serum electrolyte
values)
n Asymptomatic urinary abnormalities (e.g., gross or microscopic hematuria, proteinuria,
microalbuminuria)
n Changes in urinary frequency or problems with urination (e.g., polyuria, nocturia, urgency)
n New-onset hypertension
n Worsening edema in dependent areas
n Nonspecific symptomatologies (e.g., nausea, vomiting, malaise)
n At times symptoms can be specific (e.g., ipsilateral flank pain in those with obstructing
nephrolithiasis)
n Incidental discovery of anatomic renal abnormalities on routine imaging studies
(e.g., horseshoe kidney, congenitally absent or ptotic kidney, asymmetric kidneys,
angiomyolipoma, renal mass, polycystic kidneys)