Starvation Ketosis: A Rare Cause of Metabolic Acidosis

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As a child growing up in India, I have seen several family members performing ritual fasting. Fasting is a ubiquitous religio-cultural practice that is found, in varying forms, across the world. The month-long Ramadan and Buddhist Lent fasts are examples of religious observances practiced by followers of Islam, and Buddhism, respectively. These fasts are characterized by a documented impact on metabolic health, which can be minimized by well-known management strategies.The practice of fasting is a major part of Hinduism and can range from light restriction to extreme abstention. Mahatma Gandhi was a fervent supporter of fasting by religious conviction and as a way of freeing oneself of the constraints of the body. He used fasting as a means of exerting political pressure and engaged in several hunger strikes to protest with non-violence.

In the western countries, starvation ketosis or ketoacidosis has been reported in individuals with strict dieting (e.g.carb-restricted, ketogenic diets or Atkins diet), extreme exercise, and rarely with malnutrition. Few cases of starvation-induced ketoacidosis during pregnancy and lactation, and during the perioperative period have also been reported in literature.

I saw a young non-verbal woman with quadriplegia who was admitted from a nursing home with a two-day history of worsening abdominal pain and leakage around her percutaneous endoscopic  gastrostomy (PEG) tube site. Her medical history was significant for severe developmental delay and chronic constipation. She was afebrile and the rest of the vitals were stable. Her PEG tube feeds had been stopped one day prior to the hospital admission due to abdominal pain. Additionally, she received small doses of iv morphine for pain control. Due to no oral intake, she was maintained on isotonic intravenous fluids.

Laboratory blood work revealed  high anion gap metabolic acidosis (HAGMA). I started going down the GOLDMARK mnemonic for differential diagnosis of HAGMA to ascertain the cause.

Serum blood glucose, lactate and salicylate levels were normal. Alcohol was not detectable in serum, and there was no known exposure to any toxins. Osmolal gap was not elevated. Urine pregnancy test was negative. Urine analysis showed significant ketonuria. Serum beta-hydroxybutyrate was negative.

After ruling out the common causes of acute metabolic acidosis (lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols, uremia, and acute kidney injury), we concluded starvation ketosis was the cause of HAGMA due to elevated urinary ketone levels.

In clinical practice, fasting or starvation is seldom suspected to be the cause of significant metabolic ketoacidosis. Ketone bodies, which are water-soluble, fat derived fuel  are produced by the liver during the time of glucose deficiency. These ketone bodies are used by body tissues for energy generation, when there is limited glucose availability. Additionally, starvation results in decreased insulin and increased lipolysis. The resulting increase in the delivery of free fatty acids to the liver exceeds the capacity of acetyl-CoA to enter the Krebs cycle,which is then diverted into ketogenesis. In otherwise healthy individuals, mild ketosis (ketoacid concentration of about 1 mmol/L) develops generally after 12-14 hours of fasting and arterial pH remains above 7.3.

Since the degree of ketoacidosis usually remains relatively mild, the term "ketosis" is typically used rather than "ketoacidosis." But starvation combined with physiological stress can lead to increased anion gap and ketoacidosis.This usually occurs when there is a relatively large glucose requirement, as occurs with fasting in the very young (eg, normal neonates generally have some degree of ketosis for several days), or in pregnant or lactating women.

Our patient was started on a D5-half NS drip. Following an exchange of her PEG tube, feeding was restarted. The metabolic acidosis resolved within two days and the patient was discharged back to the nursing home. This was a great learning case for me. It is consults like these that make nephrology so challenging and exciting!

Read this excellent review article on ketone bodies.

Post by Manasi Bapat, nephrology fellow at Icahn School of Medicine, Mount Sinai, NY and NSMC Intern 2018

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