Arctic
Want to know what toxin in the local diet affected Artic explorers in the 1800s but not native people? Which body part reflects brain swelling? What did the ancient Egyptians use to treat night blindness?
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called Arctic. Want to know what toxin in the local diet affected Artic explorers in the 1800s but not native people? Which body part reflects brain swelling? What did the ancient Egyptians use to treat night blindness? Listen to find out.
Today's episode starts in Alaska where you’re moonlighting in an emergency department, planning to combine it with a few days of vacation afterwards. You've read up on frostbite and hypothermia in preparation. Your first patient has neither of these problems, but is complaining of a headache. He's a 50-year-old man with the worst headache of his life and blurry vision. He can barely see and in addition is having visual spots and flashes. He also reports generalized malaise and fatigue along with nausea and abdominal pain. He denies fever, neck pain and all other symptoms. His only past medical history is significant for a gastric bypass 10 years ago, ie weight loss surgery. He doesn't take any medicines or supplements, and denies tobacco, alcohol or drugs. He works as a truck driver.
As usual, we start with a physical exam. His temperature is 98.5 Fahrenheit or 36.9 Celsius. His heart rate is 80 bpm, his blood pressure is 130/80, his respiratory rate is 18 and oxygen saturation 100%. Completely normal. His physical exam is also completely unremarkable except for his visual acuity. He can barely read the largest letters on the bottom line of the eye chart.
So far, this appears to be a very straightforward case with a clear diagnostic approach. When you go to the emergency department with a headache and say it's the worst headache of your life, we immediately start down a path to rule out meningitis/encephalitis and subarachnoid hemorrhage, due to causes like a ruptured aneurysm.
First, we order a CT scan of the head and some basic lab work. Second, if those are negative, in many cases we perform a lumbar puncture, or a spinal tap. CT scans occasionally miss small amounts of blood in the brain. To avoid missing this life-threatening diagnosis, we send the spinal fluid to the lab to check for blood and infection. You also order pain medicine to treat the headache.
On further reflection, while waiting for the results, you note a few unusual features. Migraines commonly cause severe headaches and visual changes; our patient has no prior history. Anyone can have a migraine, but onset at his age is unusual. In addition, he's complaining right upper quadrant pain, though he didn’t have tenderness there on exam. It’s not uncommon for patients to have both headaches and abdominal pain with things like stomach viruses or the flu. It is unusual with a patient complaining of the worst headache of their lives to also complain of abdominal pain.
His CT is normal, no bleeding, brain mass, or any other abnormality. His lab work shows elevation in his liver function tests, but is otherwise unremarkable. You’re not sure exactly what it means, you are sure it’s not an emergent issue. The headache is.
You go back to check on him and convey the results. He says the pain medicine hasn’t helped the headache. The next step is a spinal tap. After getting the needle into the thecal sac containing the spinal fluid, the first step is to measure the pressure, a reflection of the pressure in the fluid around the brain. You attach a manometer, along, thin glass tube, to the end of the needle. As soon as you attach it, CSF shoots out the top of the apparatus. Uh oh. This means the CSF pressure is more than 30 mmHg. Normal pressure is around ten mmHG, meaning he has intracranial hypertension. You send a few cc of CSF to the lab for analysis.
As you remove the needle and clean up, you reflect on diseases causing intracranial hypertension as you do so. The list includes things like meningitis, encephalitis, intracranial hemorrhage, tumors, lupus, venous sinus thrombosis, and endocrine diseases, like polycystic ovary disease. You order an MRI for further evaluation. However, this isn't a neurology podcast. It's a toxicology podcast.
But first Question number 1. Which body part shows intracranial hypertension when present?
A. Eyes
B. Lower back
C. Nose
D. Neck
Answer: A. The eyes. Papilledema is swelling of your optic nerve, reflecting increased intracranial pressure. If you look into the back of the patient’s eyes, you can see this swelling. It’s difficult to do, while technically possible in the ED, it often requires a dilated eye exam and an ophthalmologist to be able to see it.
Let’s focus on toxins causing increased intracranial pressure. Interestingly, some antibiotics, classically, tetracycline, also penicillin and doxycycline. Steroids like prednisone and oral contraceptives. Lithium. Lead and ketamine.
His lumbar puncture comes back negative, no sign of meningitis or encephalitis, no evidence of bleeding. His MRI is also negative. This is all good news, but leaves us with no idea what’s causing his intracranial hypertension.
Having ruled out the truly emergent problems, you take another look through his chart. There is one clue. The elevated liver function tests. Steroids can cause both liver disease and intracranial hypertension. However, the pattern of the liver tests is wrong and the patient denies medicines or supplements.
Question 2. Time to Pick Your Poison. This is classic for which vitamin toxicity?
A. Vitamin A
B. Vitamin B12
C. Vitamin C
D. Vitamin D
The answer is A. These are the classic symptoms of hypervitaminosis A or vitamin A toxicity. It’s a rare diagnosis, so confirmation would be important, we wouldn’t want to confuse it for some other rare disease. You can send a Vitamin A level, it will take a week or so to come back and can be difficult to interpret. The gold standard is a liver biopsy. It shows characteristic findings of hyperplasia or swelling of stellate cells, formerly called Ito cells with fluorescent vacuoles stuffed with vitamin A.
The biopsy will probably take a few days. In the meantime, our patient still has a headache, and still has blurry vision. We need help from neurology and we need to admit him to the hospital for ongoing treatment. If the intracranial hypertension gets worse, he’ll progress to vision loss, seizures and coma.
Neurology recommends treatment with acetazolamide. It’s a diuretic, ie a water pill. It doesn’t affect vitamin A, but can reduce increased intracranial pressure. It’s the same drug we use to treat cerebral edema due to altitude sickness. Steroids may help. I know I said earlier they can cause intracranial hypertension, but not in the short term. If medicines don’t help and he gets worse, you can actually drain out the CSF with a therapeutic spinal tap.
You order the medicines per neurology recommendations and get him admitted to the hospital. Likely to the ICU for frequent neuro checks to make sure he doesn’t deteriorate.
Putting all of this in motion gives you a chance to ask the biggest question. Where did the massive amount of vitamin A come from? How was our patient exposed? He mentioned a gastric bypass? Could that be the culprit? No. Patients with bariatric surgery are at risk for malabsorptive diseases, meaning not extracting enough nutrients from food. They’re actually at risk for low vitamin A levels.
A common source of hypervitaminosis A is supplements. Patients can take way too much. You ask him again about supplements and he emphatically says no. You tell him you suspect vitamin A toxicity. A surprised look crosses his face. After some further discussion, the source of his exposure becomes clear.
Question number 3, eating which of the following results in high vitamin A exposure?
A. Quails
B. Polar bears
C. Puffer fish
D. Mushrooms
Answer is B. polar bears. Specifically polar bear livers. Our patient ate part of a polar ber liver a few days ago. He’s a truck driver, as mentioned in the history and says he’s been having difficulty with night vision, nearly striking a pedestrian after dark one month ago. Distraught, he did some research online, finding night blindness can be due to low vitamin A levels, which he also found could result from his gastric bypass. Rather than visit his primary care doctor to have vitamin A levels checked, and supplementation recommended, etc, he decided to fix it himself. Why? He recently lost his medical insurance due to a job change.
Our patient’s background is Inuit, native Alaskan. His mother sent him some polar bear meat, and at his request the liver. She advised him not to eat it. They both know polar bear livers are toxic, due to high levels of vitamin A. Ignoring her warning, our patient ate a few bites, hoping to improve his vision and expecting to avoid toxicity. What our patient didn't realize was just how toxic polar bear livers are. Let's talk a little bit about vitamin A toxicity and then come back to our patient.
Question 4. What is another name for Vitamin A?
A. Thiamine
B. Niacin
C. Ascorbic Acid
D. Retinol
Answer: D. Retinol. Vitamin A refers to a group of retinoids, including retinol Vit A1. Knowing this gives us insight into how Vitamin A works. Retinoids have multiple functions in the body, responsible for growth and development of embryos, immune system function, and are critical for vision, especially night vision. They maintain growth and development of epithelial cells especially related to mucus and keratin. Thus the use of retinols in skin cream for aging, acne and inflammation.
Vitamin A deficiency is rare in the US and western Europe due to plentiful dietary exposure. It is found in liver, fish, eggs and dairy products. It occasionally occurs after gastric bypass, with inflammatory bowel disease like Chron’s and is common in cystic fibrosis. Deficiency is more common in African and Asia. A fascinating fact I didn’t know before I did this episode is that deficiency increases the risk of death from infection, especially measles and infectious diarrhea.
Vitamin A deficiency also causes night blindness and problems including complete vision loss. It causes skin changes, due to disappearance of mucus cells and replacement of normal epithelium with a keratinized or dead, tough epithelium. Resulting in dry, peeling skin, broken fingernails and hair loss. In fact, its keratinization of the cornea that causes blindness.
Perhaps our patient’s night blindness was due to vitamin A deficiency. Now he definitely has the opposite problem. Vitamin A toxicity can be acute, as in the case of our patient, or chronic. 10,000 international units of vitamin A is a generally safe amount. Toxicity starts around 25 to 35 international units.
Our patient has typical hypervitaminosis A symptoms, including blurry vision, increased intracranial, pressure, and evidence of liver damage. Vitamin A is stored inside liver cells, if you eat or take too much, the cells swell due to excessive storage, resulting in cell death and liver cirrhosis. The pathophysiology of intracranial hypertension is not well understood, but vitamin A may disrupt membranes, resulting in disruption of CSF outflow, and it may modify gene expression involved in CSF secretion and absorption.
Chronic exposure as I've mentioned results in different symptoms, occurring with consumption of more than 4000 international units per day for longer than six months. Most often with excessive supplement use as I mentioned. Chronic exposure also causes cracked and peeling skin. Interestingly, hair may become permanently curly or kinky. Mucous membranes like the mouth and nose are very dry. Patients also have severe bone pain due from changes including demineralization.
Polar bear liver toxicity has been recognized by Inuit's at least since the 1500s, aware that ingestion caused headaches and prostration. European explorers discovered this for themselves later, in the 1800s. It wasn't until 1942 though that vitamin A itself was isolated as the cause. It's not just polar bear livers. There is a lot of vitamin A in beef liver, as well as very high levels in seal livers and seal fat. Also shark, tuna, and sea bass livers.
Back to our patient. What happened? I mentioned potentially toxic exposures start around 25 to 35,000 international units of vitamin A. Polar bear livers contain extremely concentrated amounts of vitamin A. One of polar bears favorite foods is seal. Seals have extremely high amounts of vitamin A in their livers and their blubber. So to keep polar bears from becoming Vit A toxic after eating, their livers have evolved to safely store high levels of the vitamin.
Just how much? 25 to 35,000 international units per gram. For the Americans, who might be unfamiliar with a gram, it varies with weight, but for example 1 g of salt is 1/6 of a teaspoon and 1 g water is 1/5 of a teaspoon. Meaning a very, very tiny amount of polar bear liver contains a toxic amount. Our patient reports he took only a few bites, but still way more than enough to cause toxicity. A polar bear liver weighs somewhere in the neighborhood of 20 pounds and is estimated to contain enough vitamin A to kill 52 adults. For comparison, 1 g of beef liver contains only 180 international units of vitamin A. You can develop toxicity from beef and fish livers, but you have to eat a lot. Not a tiny part of a tiny bite.
Side note, eating polar bear meat is restricted in many parts of the world due to their endangered status. Native Alaskans are allowed to consume the meat which is perfectly safe health wise. The risk is only due to the liver.
Our patient continues to worsen, with increasingly severe headaches and visual changes. He develops lethargy and becomes comatose. There’s no antidote for vitamin A toxicity. Treatment is removing the exposure. Neurology does another lumbar puncture and drains off CSF to reduce intracranial pressure. The ICU continues supportive care. His liver biopsy confirms vitamin A toxicity.
Fortunately, he not only wakes up, but also recovers his vision. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
Question #5. Liver as a remedy for night blindness was recognized as far back as 1500 BCE by the ancient Egyptians and is noted in ancient Assyrian, Greek and Chinese texts. Which methods of application were used to treat night blindness?
A. Rubbing liver oil on the inside of the eyelids
B. Ingestion of liver
C. Leaning over a cooking, steaming liver so the moisture went into the eyes
D. All of the above
The answer is D. All of the above. I came across an interesting article written by a physician who grew up in the United Arab Emirates. At night, they had no electricity so it was pitch dark. His father developed night blindness. An elderly medical practitioner recommended grilling a fish liver, then applying oil to the insides of his father’s eyelids. Amazingly this worked. Ancient Egyptians knew eating liver cured night blindness and other texts recommended putting your eyes over a steaming liver so the moisture went into the eyes.
Last question in today’s podcast. We’ve discussed why polar bear livers have high Vitamin A. But why do seal livers and seal fat contain high quantities of the vitamin?
A. To help their immune systems
B. To help them grow quickly
C. To help them swim faster
Follow the Twitter and Instagram feeds both @pickpoison1 and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.