Showing posts with label Manasi Bapat. Show all posts
Showing posts with label Manasi Bapat. Show all posts

Sunday, February 11, 2018

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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Saturday, September 9, 2017

Origins of Renal Physiology at MDIBL Continues to Inspire Nephrology Fellows

2017 MDIBL Origins of Renal Physiology National Renal Fellows Course
I first discovered the Origins of Renal Physiology course on Renal Fellow Network as a medicine intern, and ever since that time, dreamt of going to the course as a renal fellow. Nate’s picture in front of the “Kidney Shed” was seared in my mind. The dream finally came true two weeks ago when I set foot on the Mount Desert Island Biological Lab (MDIBL) in Coastal Maine, and the first place I visited was indeed the Kidney Shed.

In his opening address to the fellows attending the course, Dr. Ziedel rightly said “Physiology is the pride of Nephrology”. He went on to mention the names of several luminaries who have worked at the MDIBL leading to many important discoveries. The lab has been a cornerstone of nephrology research and has been a home for the work of Homer Smith, E.K Marshall, David Evans, Franklin Epstein, and many others who have spent years working on and elucidating the fundamental concepts on kidney physiology.

In modern day practice of nephrology, we are less exposed to these fundamentals of kidney physiology that initially piqued our interest in nephrology. The Origins course is one of the many efforts made by the renal community to reconnect nephrolgoy fellows to physiology. It’s a very unique course which gives the fellows an opportunity to rub elbows with senior and distinguished renal physiologists from esteemed institutions and work with them on experiments to understand the different aspects of kidney biology.

The course consisted of 7 modules, each focusing on a functional unit of the nephron- the glomerulus, proximal tubule, thick ascending limb, distal tubule, acid-base, water homeostasis, and chloride secretion. We studied animals like zebrafish, turtles, and toad bladders. We also explored how ENaC and NKCC channels work. We delved into discussion about morpholinos and so much more. Over the duration of the course, we developed a new-found appreciation for the beauty and wonder of exploring how the kidney regulates homeostasis. We also got a sense for the profound impact MDIBL has had on the field of nephrology and physiology.

As MDIBL is in such close proximity to Acadia National Park- one of the most beautiful national parks in the world, nature is inherently embedded in the process of learning here. Most days started off with a refreshing early morning short hike which energized us to spend the entire day in the lab. On alternate days, amazing outdoor activities were planned for us after presentations of the earlier day’s work. My week at the MDIBL during this course was very memorable.

I was honored to be working closely with great mentors and met nephrology fellows from all over the US and abroad, shared interests and future aspirations and found new friends. 

All in all, an incredible experience! I would wholeheartedly endorse this conference for future fellows.

Manasi Bapat
@manasib33
2nd year Nephrology Fellow
Mount Sinai Hospital, NY

Wednesday, March 15, 2017

Lupus Podocytopathy

I recently finished my 2nd month on the consult service which was a very exciting time for me because I saw patients with every class of Lupus with different kinds of presentations. It was especially rewarding because I biopsied majority of these patients myself and then followed their course through diagnosis, initiation of immunosuppression and witnessed improvement in subsequent clinic visits. I find Lupus Nephritis most fascinating among all the GNs.
One of the most interesting cases I saw since the beginning of fellowship was of a 36 yrs. old woman who presented with joint pain, malar rash, photosensitivity, worsening generalized edema and nephrotic range proteinuria of 8 grams. She had 2 prior renal biopsies- one with a diagnosis of Minimal Change Disease and the second one 2 years ago with FSGS tip lesion and Class 2 lupus Nephritis.
On her current presentation, she met the ACR criteria of diagnosis of SLE. We biopsied her again and essentially found the exact same lesion- FSGS tip lesion with Class 2 lupus nephritis.  There were only scant mesangial deposits, no endocapillary proliferation or necrosis and weak but full house staining on IM. EM showed diffuse foot process effacement. We diagnosed her with Lupus Podocytopathy and she was started on high dose steroids and immunosuppression with MMF with subsequent rapid resolution of symptoms and proteinuria to 0.8 grams within 2 weeks. It remains to be seen how she continues to respond to the treatment and if she remains in remission. She still is likely to relapse in future and switch to a different class of lupus nephritis along her course.
Podocytopathy is a glomerular disease which occurs due to extrinsic or intrinsic primary podocyte injury. Lupus Podocytopathy occurs in association with new or relapse of SLE signs and symptoms.
It is a rare presentation of Lupus Nephritis - the reported incidence is 1.33% of patients with Lupus Nephritis. So far there have been 22 reported cases in literature. Up until the early 2000s, nephrotic syndrome in a patient with class 2 lupus was deemed as a coincidence.  The work of Dube et al, Hertig et al and Kraft et al lead to an understanding that the appearance of nephrotic syndrome in a patient with Class 2 lupus (without any endocapillary proliferation or GBM deposits) coincided with Lupus flare or appearance of Lupus symptoms. Among these patients, the nephrotic syndrome appears best correlated with podocytopathy rather than subepithelial electron dense deposits, mesangial deposits, or mesangial hypercellularity. The currently used ISN/RPS classification of Lupus Nephritis does not include Lupus Podocytopathy.
A more recent article in CJASN in April 2016 studied a cohort of 50 Chinese SLE patients (the largest so far) with diffuse Foot Process Effacement and class 1 and 2 lupus nephritis.  They included minimal change  disease (MCD) in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases.They have proposed a list of criteria to diagnose Lupus Podocytopathy and suggest revision of ISN/RPS classification of Lupus nephritis to include Lupus podocytopathy as a distinct entity. The immunologic and molecular mechanism of Lupus podocytopathy has not yet been fully studied but the T-cell abnormalities in both the disorders could be the unifying pathogenic mechanism in the occurrence of MCD or FSGS in SLE.

There is very limited data currently on the treatment of this group of patients as almost all of it comes from observational studies. But so far, we know that patients with Lupus Podocytopathy are highly steroid responsive. Those who have an FSGS lesion are prone to more relapses and incomplete remission as compared to the ones with MCD, and also need immunosuppressive agents with steroids. Both nephrologists and renal pathologists need to be aware of this entity as a cause of nephrotic syndrome in patients with SLE
Posted by Manasi Bapat, Nephrology Fellow, Mount Sinai Hospital, NY