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Liver dysfunction and severe lactic acidosis in a previously healthy man

Case Editor - Judd Flesch

Reviewed By Critical Care Assembly

Submitted by

David A. Kaufman

Assistant Professor

Mount Sinai School of Medicine

New York, NY

Shawn Knapik

Department of Veterans Affairs

New York Harbor Healthcare System

Brooklyn, NY

Submit your comments to the author(s).


A man in his eighth decade presented to his primary doctor three weeks prior to admission with easy bruising.  A complete blood count revealed low counts in all three major cell lines and a subsequent bone marrow biopsy demonstrated B-cell follicular lymphoma.  Other biochemical parameters, including tests of liver transaminases and bilirubin, were normal.  Two weeks later he developed a cough and shortness of breath and he received a diagnosis of “acute bronchitis,” for which he was prescribed azithromycin along with an inhaler of salmeterol and fluticasone.

His cough and dyspnea did not improve and he was admitted to another hospital for further evaluation. A diagnosis of liver failure was made based on elevated liver function tests (aspartate aminotransferase=995 U/L, alanine aminotransferase=552 U/L, total bilirubin=7.2 mg/dL, direct bilirubin=5.5 mg/dL); worsening pancytopenia was noted.  Evaluation of the acute liver failure did not reveal an etiology, and he was transferred to a tertiary care hospital for further evaluation and care.

Past Medical & Surgical History:
Thyroid cancer, s/p partial thyroidectomy
Diabetes Mellitus, type 2
Benign prostatic hypertrophy

Herbal medicines:
  - saw palmetto
  - milk thistle
  - chromium picolinate

Social History:
Denies excessive alcohol and illicit drug use
40 pack-year cigarette smoking history, stopped in 2004
Worked as a welder, retired for 15 years
Married, three adult children

Hospital Course:
Laboratory investigation did not reveal occult infectious hepatitis or autoimmune disease.  Diagnostic imaging of the liver revealed a large intra-hepatic mass and trans-jugular liver biopsy showed extensive hepatic infiltration by lymphoma. 

His respiratory status became increasingly tenuous and his trachea was intubated and positive-pressure mechanical ventilation was initiated. He was transferred to the ICU but suffered the rapid onset of shock despite infusions of sodium bicarbonate and norepinephrine. After a conversation with his family about his wishes for end-of-life care, further attempts at resuscitation were deferred and the emphasis of care was placed on the amelioration of pain and suffering. He died one day later with his family at his bedside.

Physical Exam

On admission to the Intensive Care Unit:

T=37.3ºC      P=93/min      BP=134/61 mmHg     RR=26/min
SaO2=98% on ambient air 
General: alert but moderate respiratory distress, able to hold a conversation despite labored breathing
Head/neck: jaundiced sclerae bilaterally; jugular venous pressure estimated to be normal
Chest: 3+ use of accessory muscles of breathing, clear breath sounds throughout
Cardiac: regular rhythm, no extrasystolic sounds
Abdomen: soft no distension, moderate RUQ tenderness, marked hepatomegaly and splenomegaly
Extremities: warm, strong pulses in all limbs, no edema
Neurologic exam: +asterixis, normal speech pattern and content


Sodium    137 mmol/L
Potassium    4.7 mmol/L
Chloride    106 mmol/L
Bicarbonate    6 mmol /L
Blood urea nitrogen    29 mg/dL
Creatinine    0.3 mg/dL
Glucose    73 mg/dL
Arterial pH    7.05
Arterial PCO2    19 mm Hg
Arterial PO2    140 mm Hg
Arterial lactate    20 mg/dL
Leukocytes    1.4 x103/mm3
Hemoglobin     8.3 g/dL
Platelets    56 x103/mm3
Albumin    1.7 g/dL
Total bilirubin    18.8 mg/dL
Direct (Conjugated) bilirubin    17.8 mg/dL
Aspartate aminotransferase (AST)    997 U/L
Alanine aminotransferase    835 U/L
Lactate dehydrogenase (LDH)    327 U/L
Prothrombin time (PT)    36 sec
International normalized ratio (INR)    2.9
Partial thromboplastin time (PTT)    36.5 sec


Portable A-P chest radiograph taken on transfer to the tertiary hospital

Question 1

What is the pathogenesis of lactic acidosis in this patient?


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