Setting: emergency department (ED)
CC: Tired, weak, and short of breath
VS: BP: 168/106 mm Hg; P: 89 beats/minute; T: 97.8°F; R: 28 breaths/minute
HPI: A 62-year-old woman comes to the ED with 1 day of severe shortness of breath and cough. She says “it came on all of a sudden” when she was largely at rest. She is extremely obese and does not move most of the time. She is adherent to her medications most of the time.
PMHX:
Congestive heart failure (CHF)
Hypertension
Obesity
Medications:
Lisinopril, carvedilol, digoxin
On the computer-based case simulation (CCS), dyspnea and serious blood pressure (BP) abnormalities are two of the main problems that need treatment and testing to be ordered before the physical is done. For dyspnea, order oxygen, oximeter, and chest x-ray (sometimes arterial blood gas [ABG]). For symptomatic hypertension, order labetalol, enalaprilat, or nitroprusside intravenously (IV).
PE:
General: morbidly obese; hard to examine
Chest: incomplete examination because of obesity, possible rales at bases
Extremities: edema; one leg more swollen than the other
Cardiovascular: no murmurs heard; no gallops
Initial Orders:
Chest x-ray
Oximeter
ABG
Oxygen
Basic metabolic panel (CHEM-7)
Electrocardiogram (ECG)
1. Hypertension increases myocardial work.
2. More work requires more oxygen (O2) consumption.
3. More O2 consumption leads to more ischemia.
4. More ischemia leads to a less mobile heart.
5. A less mobile heart exacerbates CHF.
Which medication is missing from this patient’s treatment that would lower her risk of death from CHF?
a. Spironolactone
b. Furosemide
c. Nifedipine
d. Amiodarone
Answer a. Spironolactone
Although a diuretic is good to prevent fluid overload, mineralocorticoid receptor antagonists like spironolactone and eplerenone are superior for lowering mortality. Calcium channel blockers help to control BP, but do nothing for mortality benefit in CHF.
Move the clock forward 15 minutes and look at the Interval History: The patient feels better with the oxygen, but the diagnosis is not clear. There are no clear rales, jugulovenous distention (JVD), or S3gallop.
Report:
Chest x-ray: enlarged heart; no abnormalities, clear in lung fields; incomplete study from obesity
Oximeter: 92%
ABG (on room air): pH 7.49; partial pressure of carbon dioxide (PCO2) 30 mm Hg; partial pressure of oxygen (PO2) 64 mm Hg
CHEM-7: blood urea nitrogen (BUN) 12 g/dL; creatinine 0.8 mg/dL
ECG: sinus tachycardia, right bundle branch block
The patient does not improve.
Order:
Furosemide IV
What is the site of action of furosemide?
a. Tip of loop of Henle
b. Thick ascending limb (TAL) of loop of Henle
c. Na+/K+-ATPase
d. Inhibition of aquaporins at loop of Henle
Answer b. Thick ascending limb (TAL) of loop of Henle
Loop diuretics such as furosemide, bumetanide, and indapamide do not actually work at the tip of the loop. They work at the TAL of the loop (Figure 6-1). This is the site where 25% of sodium (Na) is absorbed at the nephron. Blocking absorption at the TAL cannot be compensated for by sodium absorption at the distal tubule. This is why loop diuretics are so effective at removing fluid from the body.
Figure 6-1. Tubular sites of action of the major diuretics used in clinical medicine. (Reproduced with permission from Fuster V, et al. Hurst’s The Heart, 13th ed. New York: McGraw-Hill; 2011.)
Furosemide inhibits the Na+/K+/2Cl– pump in TAL.
After two repeated doses and urine production, the patient is still dyspneic. Prior to your receiving the patient, the ED attending ordered a computed tomography (CT) angiogram with contrast. He was concerned about a pulmonary embolus in light of the dyspnea, incomplete examination, and relatively normal chest x-ray.
Sudden Dyspnea + Clear Lungs = Possible Pulmonary Embolus
You do not agree with the diagnosis of pulmonary embolus and think this is CHF.
Orders:
B-type natriuretic peptide (BNP)
Addition furosemide
The BNP is markedly elevated. After another 30 minutes, the patient produces voluminous urine. Dyspnea improves. Furosemide is continued at high doses by your postgraduate year 1 (PGY1) intern overnight after you go home. The CT angiogram shows no clot. The physical examination (PE) is excluded.
Atrial natriuretic peptide (ANP) is produced by atrial stretch in fluid overload.
Now that the dyspnea has improved, move the clock forward to the second \day.
Orders:
Echocardiogram
CHEM-7
Troponin
Report:
Echocardiogram: decreased diastolic function; increased left ventricle (LV) thickness; 64% ejection fraction
Troponin: normal
Chemistry: BUN 28 g/dL; creatinine 1.8 mg/dL; potassium (K) 3.2 mEq/L
Loop diuretics inhibit absorption of potassium at TAL.
LV hypertrophy is from hypertension.
Later in the day, the chemistries are repeated.
BUN: 37 g/dL
Creatinine: 2.5 mg/dL
BUN-to-Creatinine Ratio
>20:1 = Prerenal Azotemia = Decreased Perfusion
<15:1 = Intrarenal Acute Kidney Injury = Acute Tubular Necrosis (ATN)
Which of the following laboratory values suggest ATN?
a. Creatinine level rising 5 points in a day
b. Urine sodium >40 mEq/L
c. Urine osmolarity >500 mOsm/kg
d. Fractional excretion of sodium (FeNa) <1%
e. Urine eosinophils
Answer b. Urine sodium >40 mEq/L
ATN is the death of kidney tubule cells. Tubule cells normally absorb sodium. If they are dead, sodium cannot be absorbed and the urine sodium level rises. Nothing raises creatinine 5 points a day. Even an anephric person with zero renal function does not increase the creatinine by 5 points in a day. High urine osmolarity is found in prerenal azotemia. A dehydrated person increases water reabsorption from the kidneys. Urine eosinophils are found in allergic interstitial nephritis.
Do not forget to move the patient out of the ED after the initial set of laboratory tests and treatments!
Contrast agents cause ATN. Look for:
• Urine sodium >40 mEq/L
• Urine osmolarity <350 mOsm/kg
The patient does not feel the rising creatinine. Her dyspnea has improved with BP control to 118/70 mm Hg.
Repeat Laboratory Test Results:
BUN: 48 g/dL
Creatinine: 2.6 mg/dL
Urine sodium: 12 mEq/L
Urine osmolarity: 840 mOsm/kg
Serum bicarbonate (HCO3): 34 mEq/L (elevated)
Which of the following do you expect in this patient?
a. Granular or muddy brown casts
b. Hansel stain positive
c. Urine specific gravity 1.001
d. Hyaline casts
e. Maltese crosses
Answer d. Hyaline casts
Hyaline casts are expected in prerenal azotemia. They are accumulated Tamm-Horsfall protein, which solidifies into a hyaline cast when the person becomes “dry.” In this patient, it is very important to make a precise diagnosis. If it is overdiuresis, you may need to give a small amount of IV fluids.
Granular or muddy brown casts occur in ATN. They are dead tubular epithelial cells. Hansel and Wright stains are used to detect eosinophils in urine in allergic interstitial nephritis. Urine specific gravity is low (<1.010) in ATN. Dead tubule cells (ATN) cannot reabsorb water, so the urine is dilute. Maltese crosses are fat bodies in urine seen in hyperlipidemia.
What is the mechanism of elevated bicarbonate level in this patient?
a. Prerenal azotemia increases bicarbonate production at the distal tubule.
b. Proximal tubule absorption of bicarbonate is increased.
c. Acid excretion at the proximal tubule is increased.
Answer a. Prerenal azotemia increases bicarbonate production at the distal tubule.
Volume contraction increases renin and angiotensin II. Increased angiotensin II (ANGII) increases aldosterone production. Aldosterone excretes acid in the distal tubule and increases new bicarbonate production.
Decreased Body Volume = Metabolic Alkalosis or Contraction Alkalosis
Tubules absorb sodium and water. Dead tubules (ATN) result in:
• Dilute urine (<350 mOsm/kg)
• High sodium level (>40 mEq/L)
Urine specific gravity approximates urine osmolarity.
• Specific Gravity 1.001 = Osmolarity <100 mOsm/kg
• Specific Gravity 1.040 = Osmolarity >500 mOsm/kg
Sodium Absorption in the Kidney.
• It is the greatest energy-using step in the kidney.
• Sixty-seven percent is absorbed in the proximal tubule.
What was the most likely etiology of the patient’s dyspnea on presentation?
a. Hypertension
b. Renal injury
c. Fluid overload
Answer a. Hypertension
Hypertension was likely the etiology of the shortness of breath in this person. Because the BUN-to-creatinine ratio later became clearly 20:1 with low urine sodium level and high urine osmolarity, it becomes clear that this is all prerenal azotemia from overdiuresis. At the beginning, it is often not clear. Contrast agents are most dangerous in those with decreased renal perfusion.
Stop medications and cancel tests on CCS by double clicking on them. CCS will always ask you to confirm everything you do two to three times.
Discontinue the diuretics and order IV fluids. Repeat the chemistry levels 12 and 24 hours later to be sure the patient is going in the right direction.
Contrast may have contributed to some kidney injury in this patient in addition to prerenal azotemia. What therapy reverses ATN?
a. Nothing
b. Bicarbonate
c. N-acetylcysteine
d. Low-dose dopamine
Answer a. Nothing
There is no therapy proven to reverse ATN. It is like sunburn. You cannot reverse ATN, you can only prevent it. Hydration, N-acetylcysteine, and bicarbonate all have some effect in preventing contrast-induced renal failure. They cannot reverse it once it has occurred. Low-dose “renal” dopamine is worthless. It is always a wrong answer.
Low-dose dopamine is useless for kidney injury.
Prevent contrast-induced renal injury:
• Give 1 to 2 L hydration.
What should be changed in chronic medications?
a. Continue spironolactone.
b. Stop digoxin.
c. Add angiotensin receptor blocker (ARB).
Answer b. Stop digoxin.
Digoxin and spironolactone have no benefit in diastolic dysfunction. There is no point in adding an ARB to an angiotensin-converting enzyme (ACE) inhibitor. The patient needs to have her BP controlled, which will avoid decompensated CHF. Use beta-blockers, ACE inhibitors, and possibly calcium channel blockers.
Repeat the chemistries to see that the BUN and creatinine levels have both started to decrease. Do it often so you know when you can stop hydration.