Refeeding Syndrome is  a set of clinical complications that typically occur in severely malnourished patients as a result of aggressive fluid and electrolyte shifts during oral, enteral, or parenteral nourishment.

What conditions put you at risk for Refeeding Syndrome? 

  • Anorexia Nervosa
  • Alcoholism
  • Cancer
  • Anything that can cause ongoing electrolyte losses (Diarrhea, vomiting, fistulas)
  • Any condition that places patients in the ICU

What are the clinical manifestations of Refeeding Syndrome? 

Prolonged malnourishment leads to decreased carbohydrate intake which reduces serum glucose and ultimately a decreased insulin secretion. As a result, energy supply to the tissues and organs of the body is maintained through lipolysis and protein catabolism which causes intracellular losses of electrolytes, particularly phosphate.

When glucose is re-introduced into the malnourished patient, insulin secretion goes up, and rapidly drives phosphate into cells (including potassium) causing a decrease in the serum concentration of these electrolytes.

  • Hypophosphatemia: See mechanism above. Insulin also causes several molecules to utilize phosphate (i.e. ATP and 2-3 DPG) which further exacerbates the hypophastatemia. The decrease in phosphorylated intermediates contributes to tissue hypoxia and subsequent myocardial dysfunction, but also causes an inability of the diaphragm to contract which can cause respiratory failure. Hypophosphatemia can also induce: rhabdomyolysis, seizures, and delirium)

 

  • Hypokalemia: See mechanism above. 

 

  • Vitamin and trace mineral deficiencies: due to decreased nutritional intake

 

  • Volume overload: insulin secretion can stimulate renal sodium absorption and retention and ultimately, fluid retention which can push a patient into congestive heart failure.

REFERENCES:

  1. Fuentebella, J., & Kerner, J. A. (2009). Refeeding Syndrome. Pediatric Clinics of North America, 56(5), 1201-1210. doi:10.1016/j.pcl.2009.06.006
  2. Hearing, S. D. (2004). Refeeding syndrome. Bmj, 328(7445), 908-909. doi:10.1136/bmj.328.7445.908

Hungry Bone syndrome is a phenomenon of post-operative hypocalcemia. It is an uncommon, but serious post-surgical sequalae of parathyroidectomy.

It is profound and sustained hypocalcaemia (often with concurrent hypomagnesaemia and hypophosphataemia) despite a normal PTH.

The primary patient demography is those with severe primary hyperparathyroidism and preoperative high bone turnover (osteitis fibrosa).

WHY? The severe hypocalcaemia is thought to be secondary to increased influx of calcium into bone, due to the sudden lose of high circulating levels of PTH on chronically elevated osteoclastic resorption.

REFERENCES

  1. Ho L-Y, Wong P-N, Sin H-K, et al. Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism. BMC Nephrology. 2017;18:12. doi:10.1186/s12882-016-0421-5.
  2. Jain N, Reilly RF. Hungry bone syndrome. Curr Opin Nephrol Hyperten 2017 Jul;26(4):250-255. doi: 10.1097/MNH.0000000000000327.
  3. J E Witteveen, S van Thiel, J A Romijn, and N A T Hamdy. THERAPY OF ENDOCRINE DISEASE: Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol March 1, 2013 168 R45-R53.

Sulfonylureas were discovered in 1942, and several have been available since the 1960s. Glyburide is a second-generation sulfonylurea, it works by increasing plasma insulin concentrations.

sulfonylurea (SU) Img Cred: Arch Med Sci. 2015

WHY THE RISK OF HYPOGLYCEMIA?

The biological effect of sulfonylureas often lasts much longer than their plasma half-life, because of receptor interaction and formation of active metabolites, persisting 24 h or more. Moreover, their half-life is prolonged in the presence of renal failure.

REFERENCES

  1. Feldman JM. Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects. Pharmacotherapy. 1985 Mar-Apr;5(2):43-62.
  2. Sola D, Rossi L, Schianca GPC, et al. Sulfonylureas and their use in clinical practice. Archives of Medical Science : AMS. 2015;11(4):840-848. doi:10.5114/aoms.2015.53304.

Prolactin (PRL) is an anterior pituitary hormone which has its principle physiological action in initiation and maintenance of lactation. It may be elevated in a variety of scenarios:

  1. Lactotroph adenomas (Prolactinomas)
  2. Drugs (i.e Anti-psychotics, SSRI, Metoclopamide)
  3. Hypothyroidism
  4. Chronic renal failure
  5. Macroprolactinemia
  6. Other physiologic causes include: pregnancy, nipple stimulation, and stress

REFERENCES

  1. Majumdar, A. and Mangal, N. Hyperprolactinemia. J Hum Reprod Sci. 2013 Jul-Sep; 6(3): 168–175.
  2. Chun, J. Hyperprolactinemia: Causes and Treatments. Clinician Reviews. 2014 February;24(2):26-27.
  3. Serri O., et al. Diagnosis and management of hyperprolactinemia. CMAJ. September 16, 2003 169 (6) 575-581.

Metformin belongs to the Biguanide class of medications used to treat Type 2 Diabetes. Metformin works by decreasing the amount of glucose produced by the liver, improving insulin sensitivity, and by increasing cellular uptake of glucose.

In patients who develop acute or chronic renal failure, the clearance of metformin is decreased resulting in an increased risk of lactic acidosis, which may have a mortality rate up to 50%. Patients who receive IV contrast fluid are at risk for contrast-induced nephropathy and if they are concurrently on metformin, they may experience potentially fatal lactic acidosis. To avoid this issue, most patients scheduled to receive IV contrast have their metformin medication stopped at the time of contrast administration for at least 48 hours after the procedure.

In some patients who have preserved renal function and are receiving small amounts of contrast (< 100 mL), stopping the metformin may not be necessary because the risk of contrast-induced nephropathy is very low in these patients.

REFERENCES
1. Baerlocher, M. O., Asch, M., & Myers, A. (2012). Metformin and intravenous contrast. Canadian Medical Association Journal, 185(1). doi:10.1503/cmaj.090550
2. Benko AFraser-Hill MMagner Pet al.Canadian Association of Radiologists.Canadian Association of Radiologists: consensus guidelines for the prevention of contrast-induced nephropathyCan Assoc Radiol J 2007;58:7987.

Various studies have demonstrated Hypocalcemia as a poor prognostic marker in patients with pancreatitis. It is often apart of severity scoring (i.e Ranson/ APACHE II) to assess the severity of pancreatitis.

HOW DOES IT CAUSE HYPOCALCEMIA?

Exact mechanism of hypocalcemia in acute pancreatitis is unknown. The proposed mechanisms include:

1) Auto digestion of mesenteric fat by pancreatic enzyme (Lipase) and release of free fatty acids, which bind calcium and precipitate out as insoluble calcium salts; dropping serum levels.

2) Later stages of pancreatitis are frequently complicated by sepsis, which becomes an important contributor to hypocalcemia. Increased circulating release catecholamines during sepsis and pancreatic break down can shift calcium intracellular.

3) Hypomagnesaemia-induced impaired PTH secretion and action may have a role

REFERENCES

  1. Egi M, Kim I, Nichol A, Stachowski E, French CJ, Hart GK, et al. Ionized calcium concentration and outcome in critical illness. Crit Care Med. 2011;39:314–21.
  2. Ahmed A, Azim A, Gurjar M, Baronia AK. Hypocalcemia in acute pancreatitis revisited. Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine. 2016;20(3):173-177. doi:10.4103/0972-5229.178182.
  3. Whitted AD, Stanifer JW, Dube P, Borkowski BJ, Yusuf J, Komolafe BO, et al. A dyshomeostasis of electrolytes and trace elements in acute stressor states: Impact on the heart. Am J Med Sci. 2010;340:48–53
  4. ondon JR, Ives D, Knight MJ, Day J. The aetiology of hypocalcaemia in acute pancreatitis. Br J Surg. 1975 Feb;62(2):115-8.C

Propranolol (Beta-blocker) decreases plasma triiodothyronine (T3) and increases plasma rT3 in a dose-dependent manner due to a decreased production rate of T3 and a decreased metabolic clearance rate of rT3.

Up to 30% reduction in conversion of T4 -> T3 at high doses (above 160 mg/day) slowly over 1-2 weeks.

HOW? Via inhibition of the 5′-monodeiodinase; enzyme that converts thyroxine (T4) to T3.

NOTE: Other Beta-blockers (Metoprolol and Atenolol) can also cause a small reduction in serum T3 concentrations.

REFERENCES

  1. Wiersinga WM. Propranolol and thyroid hormone metabolism. Thyroid. 1991 Summer;1(3):273-7.
  2. Wiersinga WM, Touber JL. The influence of beta-adrenoceptor blocking agents on plasma thyroxine and triiodothyronine. J Clin Endocrinol Metab. 1977;45(2):293.
  3. Perrild H, Hansen JM, Skovsted L, Christensen LK. Different effects of propranolol, alprenolol, sotalol, atenolol and metoprolol on serum T3 and serum rT3 in hyperthyroidism. Clin Endocrinol (Oxf). 1983;18(2):139.

Hypercalcemia can occur in the context of several granulomatous diseases including: Sarcoidosis, Wegener’s granulomatosis, Silicosis, Berylliosis, Tuberculosis, Fungal granulomas and lymphomas.

WHY? Due to pathological up regulation of the conversion of:

Calcidiol (25-hydroxyvitamin D) —> Calcitriol  (1,25-(OH2)D3) via 1-hydroxylase

by activated macrophages within the pulmonary parenchyma and granulomatous inflammation.

RESOURCES

  1. Sharma, OP. Hypercalcemia in granulomatous disorders: a clinical review. Curr Opin Pulm Med. 2000 Sep;6(5):442-7.
  2. M. Fuss, T. Pepersack, C. Gillet, R. Karmali, J. Corvilain. Calcium and vitamin D metabolism in granulomatous diseases. Clinical Rheumatology. March 1992, Volume 11, Issue 1, pp 28–36.
  3. Hypercalcaemia secondary to granulomatous disorders- a series. Malik Humayun & Tristan Richardson. Endocrine Abstracts (2012) 28 P18.

The stomach acts as a reservoir for digestion. Food will be stored and broken down in it via acid and proteases. The resulting chyme is released in a controlled manner into the small intestines. Alteration of gastric anatomy (i.e gastric bypass or bypass of the pylorus) can have profound effects on GI motility.

Early dumping occurs immediately after eating (within 10-30 mins); it is characterized by vomiting, bloating, cramping, dizziness, nausea, diarrhea, etc. The cause is thought to be due to neuroendocrine changes from a hyperosmolar load being “dumped” rapidly into the small bowel.

Late dumping typically happens 1–3 hours after a meal and is characterized by hypoglycemia, weakness, sweating, and dizziness.

WHY HYPOGLYCEMIA?

The rapid movement of food into the small intestine leads to a marked increase of carbohydrates into the small bowel.

  • This causes rapid absorption of glucose into the blood stream
  • A reactive release of insulin (hyperinsulinemic response) transpires (GLP-1 mediated) resulting in subsequent reactive hypoglycemia

REFERENCES

  1. Ukleja, A. Dumping Syndrome: Pathophysiology and Treatment.  Nutrition in Clinical Practice Vol 20, Issue 5, Oct 2005 pp. 517 – 525.
  2.  Chapter 18: Disorders of Gastric & Small Bowel Motility. Walter W. Chan; Robert Burakoff. CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 3e.

 

Iron poisoning is often listed in the classic metabolic acidosis mnemonic MUDPILES, but how does it cause an anion gap metabolic acidosis?

HOW? The mechanism appears to be multi-factorial.

  1. Acute excessive ingestion of iron causes direct corrosive damage to the GI tract.
  2. Free iron penetrates numerous organs such as the liver. It enters hepatocytes, damaging the mitochondria (disrupts oxidative phosphorylation) and increases lipid peroxidation. It also damages microsomes, and other cellular organelles.
  3. Excessive iron can affect the heart: resulting in fatty necrosis of the myocardium, increased capillary permeability, and a reduction in cardiac output.
  4. Free iron also stimulates the release of pro-dilatory agents such as serotonin and histamine resulting in hypo perfusion, anaerobic metabolism and lactic acidosis.
  5. In addition ferrous iron is converted to ferric iron; hydrogen ions are released, adding to the metabolic acidosis.

The profound damage to the liver results in: hypoglycemia, hyperammonemia, coagulation defects,

and hepatic encephalopathy occurs in the context of fulminant liver failure.
REFERENCES
  1. Goyer RA. Toxic effects of metals. Klaassen CD, ed. Casarett & Doull’s toxicology:the basic science of poisons. 5th ed. New YorkCity, NY: McGraw-Hill, 1996;715-716.
  2. Williams RJ. Biomineralization: iron and the origins of life. Nature 1990;343:213-214.4.
  3. Osweiler GD, Carson TL, Buck WB, et al. Iron. Clinical and diagnostic veterinary toxicology. 3rd ed. Dubuque, Iowa: Kendall/Hunt Publishing Co, 1985;104-106.5.
  4. Hillman RS. Hematopoietic agents: growth factors, minerals, and vitamins. Hardman JG, Limbird LE, Molinoff PB, et al, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York City, NY: McGraw-Hill,1995;1311-1340
  5. Proudfoot AT, Simpson D, Dyson EH. Management of acute iron poisoning. Med Toxicol. 1986 Mar-Apr;1(2):83-100.
  6. Greentree WF, Hall JO. Iron toxicosis. Bonagura JD, ed. Kirk’s current therapy XII small animal practice. Philadelphia, Pa: WB Saunders Co, 1995;240-242.3.