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\begin{document}

\title{Severe Hypophosphatemia in Alcohol-Induced Acute Pancreatitis: A Case
Report}



\author[1]{Usamah  Al-Anbagi}%
\author[1]{Shybin  Usman}%
\author[2]{Abdulrahman  Saad}%
\author[1]{Abdulqadir Nashwan}%
\affil[1]{Hamad Medical Corporation}%
\affil[2]{Ministry of Public Health Qatar}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\selectlanguage{english}
\begin{abstract}
Mild hypophosphatemia can be reported in some cases of acute
pancreatitis, especially in alcohol-induced pancreatitis (AIP), but
severe hypophosphatemia (0.33 mmol/L) is rarely reported, even in cases
with AIP. Here we have a case report of a 43-year-old male with
alcohol-related pancreatitis associated with a critical value of
hypophosphatemia.%
\end{abstract}%



\sloppy


\textbf{Severe Hypophosphatemia in Alcohol-Induced Acute Pancreatitis: A
Case Report}

\emph{Short title: Severe Hypophosphatemia in Acute Pancreatitis}

Usamah Al-Anbagi\textsuperscript{1}, Shybin Usman\textsuperscript{1},
Abdulrahman Saad\textsuperscript{2}, Abdulqadir J.
Nashwan\textsuperscript{3*}

\textsuperscript{1} Medicine Department, Hazm Mebaireek General
Hospital, Hamad Medical Corporation (HMC), Doha, Qatar.

\textsuperscript{2} Ministry of Public Health, Doha, Qatar.

\textsuperscript{3} Nursing Department, Hazm Mebaireek General Hospital,
Hamad Medical Corporation (HMC), Doha, Qatar.

E-mails:

Usamah Al-Anbagi: UAlAnbagi@hamad.qa

Shybin Usman: SUsman3@hamad.qa

Abdulrahman Saad: Aalanbagi@moph.gov.qa

\textbf{*Corresponding author:}

Mr. Abdulqadir J. Nashwan

anashwan@hamad.qa

Tel: (+974) 40240487

Mob: (+974) 66473549 P.O. Box 3050

Hamad Medical Corporation, Doha, Qatar

\par\null

\textbf{Informed Consent}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy

\textbf{Abstract}

Mild hypophosphatemia can be reported in some cases of acute
pancreatitis, especially in alcohol-induced pancreatitis (AIP), but
severe hypophosphatemia (0.33 mmol/L) is rarely reported, even in cases
with AIP. Here we have a case report of a 43-year-old male with
alcohol-related pancreatitis associated with a critical value of
hypophosphatemia.

\textbf{Key Clinical Message}

We urge clinicians to consider undertaking serial monitoring of the
serum phosphate levels of any patient admitted with acute pancreatitis,
especially when alcohol is involved.

\emph{Keywords: Pancreatitis; Phosphate; Hypophosphatemia; Alcohol;
Electrolyte abnormalities}

\textbf{Introduction}

Acute pancreatitis is not listed in the causes of severe -critical
value- hypophosphatemia. (1) There are few major conditions which can be
associated with symptomatic hypophosphatemia, the conditions are chronic
alcoholism, intravenous hyperalimentation without phosphate
supplementation, urinary phosphate-wasting syndromes and during
treatment of diabetic ketoacidosis. (2) There are four common mechanisms
that lead to hypophosphatemia, which are the redistribution of phosphate
from the extracellular fluid into inside the cells, the decrease in
absorption of phosphate from the intestine, removal of phosphate by
kidney replacement therapies and increased urinary phosphate excretion
through urinary system. (2)

\textbf{Case Presentation}

A 43 years old gentleman, presented to the Emergency department of our
hospital with severe periumbilical abdominal pain, fever and recurrent
vomiting for the past 2 days. He is a smoker and imbibes alcohol
occasionally with no known comorbidities or regular medications. He had
consumed alcohol 4 days prior to presentation to the hospital. He had
mild diffuse abdominal discomfort and nausea after consuming alcohol.
The symptoms worsened over the next few days until he presented to the
hospital with severe symptoms. His fever was of low grade. The abdominal
pain was limited to the periumbilical area and had no radiation.
Vomiting was non-projectile. The initial vomitus contained food
particles while later he vomited scanty amounts of green fluid only. He
claims to have vomited 10-13 times per day prior to presentation.

He had no chills, rigors, dysuria, diarrhea, cough, breathlessness,
chest pain or throat pain.

On physical examination, he was tachycardic (HR:123/mt) and had high BP
(144/103 mmHg). His respiratory rate was 21/mt and SpO2 was 96\% on room
air. He was afebrile (Temp: 37.1\selectlanguage{ngerman}°C). His weight was 64kg. He had no
pallor, icterus, cyanosis, clubbing or edema. His chest was clear with
no added or adventitious sounds. No abnormality was detected in the
cardiovascular system.

Abdominal examination revealed mild upper abdominal tenderness only. No
visceromegaly, guarding, or evidence of free fluid was detected.
Examination of the nervous system was also within normal limits.

The findings of the imaging tests done as part of management and the
x-ray chest (PA view) showed bilateral accentuation of vascular markings
in the lung fields with no obvious pneumonic consolidation. The
mediastinal and cardiac shadows were normal. There was no pleural
effusion. The thoracic cage was normal. The x-ray of the abdomen showed
nonspecific bowel gas pattern and no air-fluid fluid levels or free
intraperitoneal gas.

Abdominal ultrasound (USG) of the showed only fatty liver. But the
pancreas was obscured by bowel gas. There were no sonographic features
of acute cholecystitis or cholelithiasis. Liver appeared normal in size
measuring 14.9 cm, and it showed increased echogenicity. No focal
lesions or intrahepatic biliary radicles dilatation was seen. Common
bile duct (CBD) was not dilated - measuring 3mm in diameter. Gallbladder
was well distended. No wall thickening, cholelithiasis or
pericholecystic fluid.

The patient was diagnosed with acute alcoholic pancreatitis based on the
history, examination and the high lipase level. The patient received two
liters of normal saline followed by another two liters of 5\% dextrose
in normal saline (DNS) as continuous infusion. The serum phosphate was
assayed on the 2\textsuperscript{nd} day and it was at a critical value
(0.25 mmol/L). Phosphate replacement was started initially with 20 mmol
of sodium glycerophosphate as an intravenous slow infusion over 8 hours
which was followed by oral potassium/sodium phosphate tablet (Neutra ®)
at a dose of 250mg 3 times a day. This led to progressive correction of
phosphate levels. He was discharged on the 4\textsuperscript{th} day of
admission with the serum phosphate level and the other laboratory tests
having returned to normal values.

\textbf{Discussion}

Sever (critical value) hypophosphatemia is rarely reported as one of the
complications in acute pancreatitis and, has been attributed mainly to
the alcohol abuse (3-6). The patient with alcohol use disorder is at
risk to get severe hypophosphatemia, particularly if been admitted to
the hospital. This sequence is mostly due to underlying chronic
phosphate depletion from the body, complicated by acute shifts of
phosphate from the extracellular into the intracellular compartment. (4)

Hypophosphatemia can lead to a variety of symptoms and clinical
manifestations (4). The manifestations depend in large part upon the
chronicity and severity of the phosphate depletion, it includes muscle
pain, bone pain, muscle weakness, altered mental status and numbness,
with seizure and even coma in severe life-threatening hypophosphatemia.

Although phosphate depletion is common in admitted patients with alcohol
use disorder, the drop in the phosphate level (to less than 0.32
mmol/L), may not become obvious and prominent until twelve to thirty six
hours post admission, and it is attributed to movement of phosphate form
extracellular into intracellular part (7, 8).

Two factors may contribute to this shift. The first is intravenous
dextrose-containing solutions that are usually administered in such
situations. Glucose in blood stimulates the release of insulin from
pancreas, which promotes phosphate uptake by the cells as phosphorylated
glucose intermediates (8). If intravenous dextrose infusion is
discontinued, a movement of phosphate into cells may still occur because
of refeeding-induced insulin release to the blood (9-10). Even a small
amount of 5\% dextrose can lead to hypophosphatemia (10-12).

The second factor is acute respiratory alkalosis induced by
hyperventilation as a complication of alcohol withdrawal. The increase
in extracellular pH (Potential of hydrogen) produces a similar change in
pH inside the cells since carbon dioxide (CO2) can rapidly diffuse
across cell membranes. The ensuing intracellular increase in pH
(alkalosis) stimulates intracellular phosphofructokinase, leading to an
increase in glycolysis process and then movement of phosphate into
cells. (13)

For our patient, he had one of the above-mentioned conditions, most
notably the dextrose infusion he received, which had likely contributed
to the drastic decrease of his serum phosphate level. Hypophosphatemic
patients with alcohol use disorder may complains with skeletal muscle
myopathy due to both alcohol effect and phosphate depletion, they also
are at risk of developing rhabdomyolysis (9).

\textbf{Conclusion}

Acute pancreatitis is not listed in the causes of severe -critical
value- hypophosphatemia. Thus, we highly suggest undertaking serial
monitoring of the serum phosphate levels of any patient admitted with
acute pancreatitis - especially when alcohol related.

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

The article describes a case report. Therefore, no additional permission
from our Ethics Committee was required (MRC-04-22-709\textbf{)} .

\textbf{Consent for publication}

The consent for publication was obtained from the patient.

\textbf{Availability of data and material}

All data generated or analyzed during this study are included in this
published article.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

This study was not funded.

\textbf{Authors' contributions}

UA, SU, AS, AJN: Data Collection, Literature Search, Manuscript
Preparation

All authors read and approved the final manuscript

\textbf{Acknowledgments}

Open Access funding provided by the Qatar National Library.

\textbf{Table Legends}

Table 1. Laboratory investigations

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Rizos E, Alexandrides G, Elisaf MS. Severe hypophosphatemia in a
  patient with acute pancreatitis. JOP. Journal of the Pancreas.
  2000;1(4):204-7.
\item
  Lachter J, Keider S, Eidelman S (1986) Hypophosphatemia and idiopathic
  pancreatitis. Am J Gastroenterol 81(12):1221--1222 {[}PMID: 3788937{]}
\item
  Marinella MA. Refeeding syndrome and hypophosphatemia. J Intensive
  Care Med 2005; 20:155.
\item
  De Marchi S, Cecchin E, Basile A, Bertotti A, Nardini R, Bartoli E
  (1993) Renal tubular dysfunction in chronic alcohol abuse: effects on
  abstinence.NEngl JMed 329:1927--1934 {[}PMID:8247056{]}
\item
  Sacks DB, Berman MC (1985) Hypophosphatemia in acute pancreatitis. S
  Afr Med J 68:87--90 {[}PMID: 2409610{]} Loven L, Larsson J, Lennquist
  S (1984) Hypophosphatemia and disturbed phosphate metabolism in
  alcoholic pancreatitis. Acta Chir Scand 150:269271 {[}PMID: 6464628{]}
\item
  Lachter J, Keider S, Eidelman S (1986) Hypophosphatemia and idiopathic
  pancreatitis. Am J Gastroenterol 81(12):1221--1222 {[}PMID: 3788937{]}
\item
  Wesson L (1997) Homeostasis of phosphate revisited. Nephron
  77:249--266 {[}PMID: 9375817{]}
\item
  Knochel JP. The pathophysiology and clinical characteristics of severe
  hypophosphatemia. Arch Intern Med 1977; 137:203.
\item
  Knochel JP. Hypophosphatemia in the alcoholic. Arch Intern Med 1980;
  140:613.
\item
  Miller DW, Slovis CM (2000) Hypophosphatemia in the emergency
  department therapeutics. Am J Emerg Med 18(4):457--461
\item
  MacLeodDB, MontoyaDR, Fick GH, JessenKR (1994) The effect of 25 grams
  IV glucose on serum inorganic phosphate levels. Ann Emerg Med
  23(3):524--528
\item
  Thompson JS, Hodges RE. Preventing hypophosphatemia during total
  parenteral nutrition. JPEN J Parenter Enteral Nutr 1984; 8:137-9.
  {[}84188768{]}
\item
  Hoffman RS, Weinhouse GL, Traub SJ, Grayzel J. Management of moderate
  and severe alcohol withdrawal syndromes. UpToDate. Waltham (MA):
  UpToDate. 2011.
\end{enumerate}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Laboratory parameters & On admission & 2\textsuperscript{nd} day of
admission & upon discharge & Reference values\tabularnewline
\midrule
\endhead
Serum phosphate (mmol/L) & Not done & 0.25 & 1.07 &
(0.8-1.5)\tabularnewline
Total leukocytes & 13 & 6.2 & 6.8 & (6.2 x10\^{}3/uL)\tabularnewline
Hematocrit & 46 & 35.4 & 41.2 & (40-50\%)\tabularnewline
Serum Potassium (mmol/L) & 4.4 & 3.5 & 4 & (3.5-5.3)\tabularnewline
Serum sodium (mmol/L) & 132 & 136 & 138 & (133-146)\tabularnewline
Serum calcium (mmol/L) & Not done & 2.3 & 2.55 &
(2.2-2.6)\tabularnewline
Serum magnesium (mmol/L) & Not done & 0.88 & 0.82 &
(0.7-1)\tabularnewline
Serum urea (mmol/L) & 7.5 & 5 & 2.1 & (2.5-7.8)\tabularnewline
Serum creatinine (umol/L) & 140 & 79 & 49 & (62-106)\tabularnewline
Serum glucose (mmol/L) & 6.5 & 6.2 & 7.1 &
(\textless{}11.1)\tabularnewline
HbA1c & 5.7\% & & & \textless{}5.7\%\tabularnewline
Serum albumin (gm/L) & 53 & 37 & 43 & (35-50)\tabularnewline
Serum total protein (gm/L) & 94 & 67 & 62 & (60-80)\tabularnewline
Serum lipase (U/L) & 485 & 356 & Not done & (13-60)\tabularnewline
Lactate (mmol/L) & 1.3 & 1.5 & 1.6 & (0.5-2.2)\tabularnewline
AST (IU/L) & 48 & 42 & 70 & (0-41)\tabularnewline
ALT (IU/L) & 44 & 32 & 50 & (0-41)\tabularnewline
Alkaline phosphatase (U/L) & 100 & 67 & 64 & (40--129)\tabularnewline
TSH (mIU/L) & 1.52 & & & (0.3-4.2)\tabularnewline
FT3 (pmol/L) & 17.9 & & & (11-23.3)\tabularnewline
Serum total bilirubin (mg/dl) & 34 & 21 & 17 & (0-21)\tabularnewline
Serum chloride (mmol/L) & 84 & 100 & 96 & (95-108)\tabularnewline
Serum bicarbonate (mmol/L) & 10 & 22 & 26 & (22-29)\tabularnewline
24-hr urine Phosphorous (mg/24 hr) & Not done & \textless{}1.1 &
&\tabularnewline
Serum triglycerides (mmol/L) & 3.4 & Not done & 1.2 &
(\textless{}1.7))\tabularnewline
\emph{HbA1c: hemoglobin A1C; AST: aspartate aminotransferase; ALT:
alanine transaminase; TSH:} \emph{thyroid stimulating hormone; FT3:}
\emph{free triiodothyronine} & \emph{HbA1c: hemoglobin A1C; AST:
aspartate aminotransferase; ALT: alanine transaminase; TSH:}
\emph{thyroid stimulating hormone; FT3:} \emph{free triiodothyronine} &
\emph{HbA1c: hemoglobin A1C; AST: aspartate aminotransferase; ALT:
alanine transaminase; TSH:} \emph{thyroid stimulating hormone; FT3:}
\emph{free triiodothyronine} & \emph{HbA1c: hemoglobin A1C; AST:
aspartate aminotransferase; ALT: alanine transaminase; TSH:}
\emph{thyroid stimulating hormone; FT3:} \emph{free triiodothyronine} &
\emph{HbA1c: hemoglobin A1C; AST: aspartate aminotransferase; ALT:
alanine transaminase; TSH:} \emph{thyroid stimulating hormone; FT3:}
\emph{free triiodothyronine}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 1. Laboratory investigations}

\selectlanguage{english}
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