Intern Report 8.12

internreport

Case Presentation by Jacob Jensen, MD

Chief complaint: nausea and vomiting

HPI: Patient is a 28 year old female with past medical history of developmental delay, schizophrenia, and hypothyroidism transferred to the ED from a skilled nursing facility for nausea and vomiting. Patient is not responding to questions, she is not accompanied by family or nursing home staff, and EMS is unable to supply further details. Per EMR review, patient is often transferred to this or other nearby hospitals with similar complaints (especially the day before holiday weekends).

ROS: Could not be obtained 2/2 patient’s underlying medical presentation.

PMH: Developmental delay, schizophrenia, hypothyroidism

PSH: There is a reference to an X-lap in the EMR but no explanation as to when or why it was performed.

SHx: Patient has resided in a skilled nursing facility for at least the last 10 years

All: NKDA

Meds: seroquel, trazadone, respiredone, cogentin, synthroid,

Physical exam:
Vitals: T 36.4 Oral, HR 137, BP 49/33, RR 22, SpO2 97% on room air
General: Alert but non-verbal
Eye: Extraocular movements are intact
HENT: Normocephalic, Atraumatic, Oral mucosa is dry
Respiratory: Respirations are non-labored
Cardiovascular: Normal S1, S2, no murmurs, rubs, or gallops
Gastrointestinal: Soft, mildly distended, no rebound or guarding
Musculoskeletal: No deformity
Integumentary: Cool, dry, intact

Course in the ED:
Patient was triaged to resuscitation bay due to hypotension with tachycardia. A 16 gauge IV was started and patient was given 2L normal saline. On repeat testing, patients HR had decreased to 118 and BP had increased to 92/70.

Patient had one witnessed episode of vomiting in the ED. The vomitus smelled feculent so an NGT was placed. 300mL of yellow-green gastric contents was returned.

Basic labs were as follows; Bedside Glucose unremarkable, Lactic Acid 9.7, BMP unremarkable, CBC remarkable for leukocytosis of 13.1 with absolute neutrophil count of 9.7, coags unremarkable, urinalysis unremarkable, and urine pregnancy negative.

Chest X-ray was unremarkable.

EKG was unremarkable.

Abdominal series was obtained and read as suggestive of high-grade distal small bowel obstruction.

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The patient is transferred to the module and a surgery consult is placed. On reexamination, HR is 115, BP is 120/68. The patient is now nodding and shaking her head in response to questions. When asked if she has any pain, she indicates her abdomen. Her abdomen is still mildly distended and diffusely TTP without guarding or rebound.

Questions:
A) What is the most likely cause of lactic acidosis in this patient?

  1. Increased pyruvate production
  2. Reduced entry of pyruvate into mitochondria
  3. Accumulation of NADH
  4. Impaired gluconeogenesis
  5. Metabolization of glucose by intestinal bacteria

B) What is the best fluid replacement option in this situation?

  1. Crystalloid (Normal Saline or Lactated Ringer)
  2. Buffer therapy (0.45% saline solution with 75mmol/L of sodium bicarbonate)
  3. Blood products
  4. Albumin
  5. Hyperoncotic starch

C) What further diagnostic studies, if any, are called for?

  1. No further studies are necessary
  2. Check patient’s D Dimer
  3. Check patient’s liver function; AST, ALT, Alk. phos.
  4. Abdominal CT angiogram
  5. Exploratory laparotomy

Answers & Discussion
1) 3
2) 2
3) 6

A) What is the most likely cause of lactic acidosis in this patient?

  1. Increased pyruvate production
  2. Reduced entry of pyruvate into mitochondria
  3. Accumulation of NADH
  4. Impaired gluconeogenesis
  5. Metabolization of glucose by intestinal bacteria

B) What is the best fluid replacement option in this situation?

  1. Crystalloid (Normal Saline or Lactated Ringer)
  2. Buffer therapy (0.45% saline solution with 75mmol/L of sodium bicarbonate)
  3. Blood products
  4. Albumin
  5. Hyperoncotic starch

C) What further diagnostic studies, if any, are called for?

  1. No further studies are necessary
  2. Check patient’s D Dimer
  3. Check patient’s liver function; AST, ALT, Alk. phos.
  4. Abdominal CT angiogram
  5. Exploratory laparotomy

Discussion

  1. First a quick recap of lactate production in human cells. In glycolysis, glucose is broken down into two pyruvate molecules. This pathway produces a total of 2 ATP, and also converts two molecules of NAD+ into two molecules of NADH. In aerobic environments, the two molecules of pyruvate can then be transported into the mitochondria to participate in the citric acid cycle producing more NADH. Finally, NADH is converted back to NAD+ in the electron transport chain of the mitochondrial matrix, creating a proton gradient that is used to produce more ATP. However, the electron transport chain can not operate in an oxygen poor environment. This means that without oxygen, the cell can not convert NADH back to NAD+. The solution to this problem is anaerobic glycolysis, during which pyruvate is converted into lactate, a process which regenerates NAD+.

Jensen2

 

 

 

 

Lactate, or lactic acid, can then be further oxidized into water and carbon dioxide or used by hepatocytes as the substrate for gluconeogenesis in the liver. Of note, human cells produce the L isomer of Lactic acid while bacteria can also produce the D-isomer which is not readily metabolized by human cells and can accumulate.

This patient presented in hypovolemic shock. It is not known how long she had been in this state, but it can be assumed that she has experienced some amount of end organ hypoperfusion. Insufficient oxygen delivery will result in the inability of mitochondria to maintain the activity of the electron transfer chain, resulting in a buildup of NADH. By Le Chatelier’s principle, an accumulation of NADH will drive the Pyruvate/lactate equilibrium toward the production of more lactate. This is what is causing our patient’s lactic acidosis.

Accumulation of NADH might also be secondary to increased metabolic demands such as during a grand mal seizure or intense exercise. However, this does not appear to be the case with this patient.

Increased pyruvate production (a) occurs in patients who have enzymatic defects affecting glycogenolysis or gluconeogenesis. This would most likely present in patients younger than 28 years old. Mitochondrial dysfunction (b) might also be secondary to genetic defects or it could be 2/2 drugs that cause mitochondrial damage. Examples of such drugs include Antiretrovirals and some antibiotics such as linezolid. There is no indication that this patient is taking any such medication.

Gluconeogenesis (d) mostly occurs in the liver. Patients with impaired liver function may have elevated lactic acid levels. Because this patient had an unremarkable coag profile, it is not likely that her liver is the source of her lactic acidosis.

D-Lactic acidosis (e) can be seen when intestinal bacteria are exposed to high levels of glucose. An example of this is patients with short gut syndrome. There is no indication that this patient would have increased levels of D-Lactic acid.

 

  1. Crystalloids (a) are as effective as colloids at expanding plasma volume and saline has the advantage of being less expensive.

It has been thought that adding sodium bicarbonate to half normal saline (b) might help to buffer lactic acidosis while decreasing the chances of developing hyperchloremic acidosis, but this is controversial. At a minimum, patient’s serum pH and bicarbonate levels should be tested before beginning this therapy.

Blood replacement therapy (c) is indicated if patient is actively bleeding, or has a low hemoglobin and is symptomatic, none of which apply to this patient.

No advantage has been found for albumin (d) in hypovolemic resuscitation and hyperoncotic starch (e) is not advised over concern for kidney injury.

 

  1. After resuscitation from hypovolemic shock, this patient was found to have elevated lactic acid, leukocytosis, and small bowel obstruction. She is non-verbal, but she does indicate that she is experiencing abdominal pain even though her abdomen is soft and there are no peritoneal signs. In this instance, the physician should have a low index of suspicion for mesenteric ischemia. The “gold standard” to evaluate for mesenteric ischemia is a mesenteric angiogram, however, recent studies have shown that CT angiogram has a sensitivity of 96% and a specificity of 94%.

Jensen3

 

Abdominal pain, lactic acidosis, and leukocytosis are all very non-specific. It may be very tempting to attribute these abnormalities to the small bowel obstruction and treat for constipation (a). However, mesenteric ischemia has not yet been ruled out.

D Dimer (b) is also a very non-specific test and would have little impact on the management of this patient.

This patient’s coag profile is within normal limits. She is not jaundiced, and there is nothing in her social history to suggest liver failure. Liver function test (c) would not influence the outcome of this case.

Exploratory laparotomy (e) is necessary if the patient has signs of intestinal infarction or perforation. As patient is hemodynamically stable and is not exhibiting peritoneal signs, Ct is more appropriate at this time.

 

 

References:

  1. “Biphasic CT with Mesenteric CT Angiography in the Evaluation of Acute Mesenteric Ischemia: Initial Experience”, Radiology, October 2003. Kirkpatric et. al.
  2. “Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials”, British Medical Journal, March 1998, Schierhout
  3. Rosen’s Emergency Medicine, eighth edition, 2014, pages 1221-1224, Marx
  4. Uptodate, Causes of Lactic Acidosis, 2014 Emmett,
  5. Uptodate, Overview of Intestinal Ischemia in Adults, 2014 Grubiel and Lamont
  6. Uptodate, Treatment of Severe Hypovolemia or Hypovolemic Shock in Adults, 2014, Mandel and Palevsky

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