Accepted Manuscript

Medical Complications of Anorexia Nervosa and Bulimia

Patricia Westmoreland, MD, Mori J. Krantz, MD, Philip S. Mehler, MD, FAED, FACP

PII: S0002-9343(15)00582-3
DOI: 10.1016/j.amjmed.2015.06.031
Reference: AJM 13081

To appear in: The American Journal of Medicine

Received Date: 22 May 2015

Revised Date: 19 June 2015
Accepted Date: 19 June 2015

Please cite this article as: Westmoreland P, Krantz MJ, Mehler PS, Medical Complications of Anorexia
Nervosa and Bulimia, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.06.031.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
 ACCEPTED MANUSCRIPT

Medical Complications of Anorexia Nervosa and Bulimia

Patricia Westmoreland, MD1

Mori J. Krantz, MD2,4

PT
Philip S. Mehler, MD, FAED, FACP1,3,4

RI
1
Eating Recovery Center of Denver, 7351 E Lowry Blvd, Suite 200, Denver, CO 80230

SC
– Pwestmoreland@eatingrecoverycenter.com
2
Cardiology Division, Denver Health Medical Center, Denver, CO, 777 Bannock St.,

U
MC0960, Denver, CO 80204 – Mkrantz@dhha.org
AN
3
ACUTE at Denver Health, Denver Health Medical Center, 777 Bannock Street,

MC4000, Denver, CO 80204 – PMehler@dhha.org

M

4
Department of Medicine, University of Colorado Health Sciences Center
D
TE

Corresponding Author:

Philip S. Mehler, MD, FAED, FACP

EP

777 Bannock Street, MC 4000

Denver, CO 80204
C

303-602-4972
AC

Email: PMehler@dhha.org

Funding Source – None

Conflict of Interest – None

Word Count: 3,888

 ACCEPTED MANUSCRIPT

ABSTRACT

Anorexia nervosa and bulimia nervosa are serious psychiatric illnesses related to

disordered eating and distorted body images. They both have significant medical

PT
complications associated with the weight loss and malnutrition of anorexia nervosa as

RI
well as from the purging behaviors which characterize bulimia nervosa. No body

system is spared from the adverse sequela of these illnesses, especially as anorexia

SC
nervosa and bulimia nervosa become more severe and chronic. Here we review the

medical complications which are associated with anorexia nervosa and bulimia nervosa

U
as well as the treatment for said complications. We also discuss the epidemiology and
AN
psychiatric comorbidities of these eating disorders.
M
D
TE
EP

Keywords: Anorexia Nervosa, Bulimia, Medical Complications, Hypokalemia,

Osteoporosis
C
AC
 ACCEPTED MANUSCRIPT

INTRODUCTION

Anorexia nervosa and bulimia nervosa are serious psychiatric illnesses with

substantial morbidity and mortality. It is the psychiatric illness with the highest mortality

rate.1-7 Mortality is also increased in patients with bulimia nervosa.8 In both anorexia

PT
nervosa and bulimia nervosa, much of the increased mortality rate is attributable to the

RI
medical complications inherent to these two illnesses.

Although anorexia nervosa and bulimia nervosa are defined as separate

SC
disorders in the psychiatric Diagnostic and Statistical Manual 5th Edition (DSM-5),9 they

both fall into the category of disordered eating, driven by an irrational fear of normal

U
body weight, a desire for thinness, and leading to body image distortion.10 Cultural
AN
ideals of beauty and thinness may incite the development of disordered eating in

vulnerable individuals, who have a genetic predisposition towards anxiety and

M

perfectionism.11 Both starvation and purging may initially calm these feelings of anxiety
D

and reduce obsessions and compulsions via a serotonergic neuronal pathway.12, 13

TE

During the course of anorexia nervosa and bulimia nervosa, comorbid mental

disorders also emerge as a result of altered neurotransmitter metabolism and/ or

EP

endocrine changes that result from caloric deprivation.14-17 Almost 50% of adolescent

patients with anorexia nervosa meet criteria for at least one comorbid psychiatric
C

illness.18 Eating disorders are strongly associated with mood and anxiety disorders, and
AC

the type and severity of these comorbidities is increased in patients who have the most

severe eating disorders.19-23

In addition, patients with bulimia nervosa who have comorbid borderline

personality disorder have poorer outcomes than those without borderline personality
 ACCEPTED MANUSCRIPT

disorder when both groups are treated with psychotherapy and pharmacotherapy.24,25

Psychiatric comorbidity, as well as a history of suicidal or self-harm ideation, and

comorbid mental illnesses all confer an increased risk of death in patients with eating

disorders.25-28 Problems socializing, and difficulties with being assertive, are factors that

PT
contribute to maintaining an eating disorder. 29 Temperament traits of harm avoidance,

RI
combined with high reward dependence, are protective factors seen more commonly in

patients who recover from eating disorders.30

SC
Treatment of anorexia nervosa and bulimia nervosa is multi-dimensional. In

addition to nutritional rehabilitation, cognitive-behavioral psychotherapy, along with

U
family therapy, have been shown to be effective in treating patients with anorexia
AN
nervosa,31 although the benefit of these therapies have been mostly noted in the weight

maintenance phase of treatment.32

M

There is only minimal to moderate evidence that psychiatric medications are

D

efficacious in treating patients with anorexia nervosa. Despite the prevalence of mood
TE

and anxiety symptoms in patients with anorexia nervosa, medications used to treat

these conditions are not necessarily useful treatment adjuncts for reducing the
EP

symptoms of anorexia nervosa. In one study, fluoxetine assisted in preventing relapse

in weight-restored patients with anorexia nervosa.33 However this finding was not
C

replicated in a subsequent study.34 While there may be evidence for using

AC

antidepressants in the weight maintenance phase, antidepressants do not ameliorate

eating disorder pathology in patients who are acutely underweight.35 The poor

response to antidepressants is believed to result from starvation-induced abnormalities

in serotonin receptors.36
 ACCEPTED MANUSCRIPT

In addition to concerns regarding the efficacy of antidepressants in patients with

anorexia nervosa, there is also considerable debate as to the efficacy of antipsychotics

in treating their symptoms. Low-dose antipsychotic medications may be useful in

treating delusional beliefs regarding body image, intense ruminations about food, and

PT
the hyper-arousal and as well as anxiety induced by having to face weight

RI
restoration.37,38 Although atypical antipsychotic medications promote weight gain in

normal weight individuals, they do not have this effect in patients with anorexia

SC
nervosa.35,39 However, patients with eating disorders may not accept reassurance in

this regard. Despite the paucity of associated weight gain, there remains concern that

U
the risk of using these medications outweighs their potential benefit.40 First generation
AN
antipsychotics (typical antipsychotics) lower the seizure threshold. Side effects of

second-generation antipsychotics (atypical antipsychotics), such as orthostasis,

M

prolonged QTc, and hepatotoxicity are of concern.

D

Despite continued debate regarding the usefulness of pharmacotherapy in

TE

patients with anorexia nervosa, pharmacotherapy for bulimia is well established.

Fluoxetine (at doses of 60 mg or higher) is FDA-approved for bulimia nervosa, and

EP

other selective serotonin reuptake inhibitors (as well as other classes of

antidepressants) have been found to be useful in treating patients with bulimia

C

nervosa.32,37 The effect of fluoxetine in treating the symptoms of bulimia nervosa

AC

appears to be independent of its effects on mood, and is reportedly related to the effects

of the medication on satiety, thereby reducing binge eating.41,42 Cognitive behavioral

therapy is a well-established psychotherapeutic treatment for bulimia nervosa.32,43

 ACCEPTED MANUSCRIPT

MEDICAL COMPLICATIONS - ANOREXIA NERVOSA

Anorexia nervosa can adversely affect almost every body system. The

complications arise as a direct result of weight loss and malnutrition. However, there

are no studies which define which body mass index (BMI) is associated with a particular

PT
medical complication. The eyes may be affected by lagophthalmos, wherein the eyelids

RI
do not totally cover the eye during sleep, resulting in irritation to the cornea and mild

ocular discomfort.44 Treatment involves taping the eyes shut at night after first applying

SC
a sterile lubricant.

GASTROINTESTINAL
U
AN
Dysphagia can frustrate the ingestion of oral calories during the early stages of

refeeding. It is due to weakened and uncoordinated pharyngeal muscles. As a result,

M

patients may complain of coughing with eating or may have a history of aspiration
D

pneumonia. The diagnosis is made by a modified barium swallow test and the
TE

treatment depends on weight restoration and input from a speech therapist to define

proper food consistencies.45 Patients with anorexia nervosa have significantly slowed
EP

gastric emptying at their nadir weights which is accompanied by complaints of early

satiety, nausea and bloating.46 This gastroparesis ultimately resolves with weight gain,
C

but symptoms may respond early on to low dose, short-term usage of metoclopramide
AC

before meals. Acute gastric dilatation is a serious condition which can lead to gastric

perforation if not recognized early.47 It can occur independently as an isolated finding in

the early phases of refeeding or, it can occur as a result of the superior mesenteric

artery syndrome.48 Superior mesenteric artery syndrome is defined by the extrinsic

 ACCEPTED MANUSCRIPT

compression of the third portion of the duodenum by the superior mesenteric artery, due

to loss of a fatty tissue pad which normally maintains the angle between the superior

mesenteric artery and the aorta. Significant left upper quadrant abdominal pain with

eating, emesis during the meal and early satiety should prompt an evaluation for gastric

PT
dilatation or superior mesenteric artery syndrome, via an abdominal radiograph or CT

RI
scan. Treatment of superior mesenteric artery syndrome is aimed at weight restoration

to reconstitute the fat pad. This can be achieved by a soft or liquid oral diet or by enteral

SC
feeds via a nasojejunal tube or a percutaneously placed one.49 Acute gastric dilation is

first treated by gastric decompression with a nasogastric tube, followed by similar

U
treatments to those used in superior mesenteric artery syndrome. Just as there is
AN
slowing of the proximal gastrointestinal tract, there is also slowing of colonic function,

resulting in constipation as an accompanying symptom in anorexia nervosa.50 Osmotic

M

laxatives are useful along with reassurance that the patient’s prior bowel pattern should
D

return over a few weeks with ongoing progressive nutritional rehabilitation.

TE

Elevated liver transaminases occur frequently at patient’s nadir weights.51 This

generally represents apoptosis, a programmed hepatocyte death as a result of

EP

malnutrition. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

are the most frequently affected in a range of 2-4 times elevated, but severe elevations
C

have also been reported to occur.52 ALT is more elevated than AST. The prevalence of
AC

liver enzyme abnormalities correlates with lower BMI’s, hypoglycemia and the

development of refeeding hypophosphatemia.53 Progressive nutritional support will

resolve these elevations over the first few weeks of refeeding. Alkaline phosphatase

and bilirubin are not commonly affected. Less frequently, elevations of the AST and
 ACCEPTED MANUSCRIPT

ALT may be due to steatosis as a result of actual refeeding. A liver ultrasound can help

elucidate the cause since in steatosis, a fatty enlarged liver will be noted.54

CARDIAC

PT
As noted above, anorexia nervosa has the highest mortality of any psychiatric

RI
disorder. Sudden cardiac death along with other medical complications and suicide

account for about 60% of the deaths. The exact cause of sudden death in anorexia

SC
nervosa remains unknown. Autopsy studies do not reveal evidence of obstructive

coronary artery disease.55 It has been postulated that alterations in cardiac conduction

U
and repolarization contribute to heightened mortality though a single unifying
AN
mechanism. Bradycardia is commonly noted in patients and reflects heightened vagal

tone in the setting of substantial weight loss. This often recovers with restoration of body
M

weight. A resting heart rate of less than 60 beats per minute, for example, was seen in
D

95% of patients in a consecutive series.56 Sinus bradycardia in and of itself does not
TE

require specific therapy, but current guidelines recommend hospitalization for a heart

rate less than 40 beats per minute. High-grade atrioventricular block is exceedingly rare
EP

and suggests underlying structural heart disease that may be unrelated to anorexia

nervosa itself. Temporary pacemakers are rarely required. Persistent junctional rhythm
C

has been described among patients with severe anorexia nervosa, which may be
AC

extinguished with exercise.57,58

Patients may present with prolongation of the rate-corrected QT (QTc) interval on

surface electrocardiography and a commonly held belief was that this is the primary

cause of sudden cardiac death. However, this relationship is confounded by concurrent

 ACCEPTED MANUSCRIPT

QTc-prolonging medications and depletion of serum potassium and magnesium levels.

In a series of patients with severe anorexia nervosa, marked QTc interval prolongation

(>500 ms) was actually uncommon in the absence of contributing factors.59 Similarly,

Facchini and colleagues observed 29 patients with anorexia and found marked QTc-

PT
prolongation in only 2 individuals.60 Both had profound hypokalemia, and after

RI
potassium repletion, the QTc interval normalized. Therefore, to date, an independent

causal pathway between anorexia nervosa, QTc-prolongation, torsade de pointes, and

SC
sudden cardiac death have not been demonstrated. Expectant management of delayed

repolarization is generally adequate and includes electrolyte repletion, discontinuation of

U
QTc-prolonging medications, and serial 12-lead electrocardiography.
AN
Severe anorexia nervosa is also known to change cardiac structure. Many

patients develop left ventricular atrophy and subsequent annular changes that lead to
M

mitral valve prolapse. Patients occasionally develop pericardial effusions, which are
D

generally self-limited and resolve with weight restoration. Among the most prominent
TE

cardiovascular structural abnormalities is a substantial reduction in left ventricular

myocardial mass with preserved left ventricular systolic function. This is generally
EP

reversible with refeeding. One study demonstrated myocardial fibrosis/scar manifested

by late gadolinium enhancement on magnetic resonance imaging (MRI) in nearly a

C

quarter of patients.61 Although echocardiographic atrophy and fibrosis by MRI have

AC

been demonstrated, histologic abnormalities in the heart have been poorly

characterized until very recently: a published autopsy report showed left ventricular

atrophy with endocardial and interstitial fibrosis, focal myxoid material deposition with

mast cells, and increased cytoplasmic lipofuscin.62 Although most cardiac structural
 ACCEPTED MANUSCRIPT

abnormalities are reversible in this condition, the presence of myocardial scar suggests

that malignant arrhythmias remain a possible mechanism of increased mortality in this

disease.

PT
PULMONARY

RI
As opposed to the cardiac system, the lungs are not adversely affected for the

most part. There appear to be some pulmonary function test abnormalities associated

SC
with anorexia nervosa which are similar to those seen with emphysemia.63 It is not clear

if this impairment recedes with refeeding. Spontaneous pneumothorax has been

U
reported in anorexia nervosa along with prolonged air leaks.64
AN
HEMATOLOGY
M

As anorexia nervosa becomes worse, there is trilinear hypoplasia causing

D

anemia, leukopenia and thrombocytopenia. Anemia occurs in 40% of these patients,

TE

with leukopenia noted in 30% and thrombocytopenia in about 10%.65 The cytopenia are

due to gelatinous marrow transformation with atrophy of the normal fat content in the
EP

marrow and replacement by a mucopolysacharide.66 Iron deficiency is not typically

found and red cell indices are normal. Although often neutropenic, surprisingly, these
C

patients do not appear to be more susceptible to infectious complications.67 However,

AC

they also do not manifest a typical febrile response to infections and inflammatory

markers are suppressed, which can cause a delay in the diagnosis of an infection.68

The cytopenias resolve with weight restoration; growth factors are not indicated in

anorexia nervosa.69 Very recently, plasma levels of vitamin B12 and folate have been
 ACCEPTED MANUSCRIPT

found to be increased. The increase is artificial as it was found to be due to hepatocyte

dysfunction with leakage of the vitamins from these cells.70

MUSCULOSKELETAL

PT
Osteoporosis is common in anorexia nervosa and occurs early in the disease.71

RI
Decreased bone density is evident after just one year of anorexia nervosa,

notwithstanding the relatively young age of these patients. The risk of subsequent

SC
fragility fractures is markedly elevated, both in adults and adolescents with anorexia

nervosa.72,73 Fracture incidence increases soon after diagnosis of anorexia nervosa

U
and remains so many years later. This is one of the rare complications of anorexia
AN
nervosa which may leave irreversible damage even after recovery. Thus, the need for

obtaining bone density testing in all patients with a disease duration of more than one
M

year. In contrast to postmenopausal osteoporosis, in anorexia nervosa the loss of bone

D

mineral density is due to both decreased bone formation along with increased bone
TE

resorption. Also, trabecular bone is more affected than cortical bone. Yet, the exact

etiological factors involved in their loss of bone density is not clear. Putative factors
EP

include the overlap between the normal accrual of peak bone mass and the age of

onset of anorexia nervosa, along with the typical hypogonadal state, elevated cortisol
C

levels and growth hormone resistance found in anorexia nervosa as will be described
AC

below.

There are currently no treatments specifically approved for the osteoporosis of

anorexia nervosa. Weight gain and resumption of menses are key and are associated

with significant increases in spine and hip bone mineral density.74 However estrogen
 ACCEPTED MANUSCRIPT

therapy does not appear to be of much value in anorexia nervosa. Many randomized

controlled trials have found it to be ineffective, a fact which is underappreciated in the

medical community.75-77 Also, the withdrawal bleeding associated with their usage can

mislead patients into believing they are getting better. Transdermal estrogen patches

PT
have shown promising results in adolescents.78 Calcium and vitamin D by themselves

RI
do not restore bone density.79 Bisphosphonates have been shown to be effective in

anorexia nervosa with an increase of 3-4% in spine bone mineral density after twelve

SC
months of treatment.80 Teriparatide, a recombinant parathyroid hormone, has recently

demonstrated very favorable effects in this population.81 There are no data as yet with

U
denosumab.82 Testosterone therapy may be effective in male patients with anorexia
AN
nervosa who also have low serum testosterone levels. Males with anorexia nervosa

actually have more severe degrees of osteoporosis then their female counterparts.83
M
D

ENDOCRINE
TE

There are multiple endocrine abnormalities associated with anorexia nervosa.

Most patients, both female and male, are hypogonadal, due to reversion to a
EP

prepubertal state wherein pulsatile hypothalamic gonadotropin releasing hormone

(GNRH) secretion is reduced, causing low levels of follicle stimulating hormone (FSH)
C

and leutinizing hormone (LH).84 Thus, amenorrhea is commonly noted in most, but not
AC

all females with anorexia nervosa. Leptin may have a causal role in the amenorrhea.85

Resumption of menses generally occurs at the weight where the periods ceased or at

more than 90% of ideal body weight.86 Some patients, however, have prolonged

amenorrhea even after weight restoration, and fertility may be permanently adversely
 ACCEPTED MANUSCRIPT

affected.87 In males with anorexia nervosa, the low testosterone levels affect potency,

libido and muscle strength.

Cortisol levels have been noted to be elevated due to both increased adrenal

production and decreased renal clearance.88 Growth hormone levels are also noted to

PT
be elevated, but insulin growth factor-1 (IGF-1) levels are low, indicating a state of

RI
growth hormone resistance.89 Most patients have thyroid function abnormalities which

closely mimic sick euthyroid syndrome. These resolve with weight gain.90

SC
Hypoglycemia occurs as anorexia nervosa becomes more severe, as a result of

depleted hepatic glycogen stores. It is a poor prognostic sign which requires close

U
monitoring.91 There is also evidence that Type 1 diabetes may be related to the
AN
development of anorexia nervosa, although the specifics are inconclusive.92 However,

what is very clear is that some of these insulin-dependent diabetic patients realize that
M

they can induce weight loss via reducing their use of insulin, thereby causing
D

hyperglycemia and a resultant osmotic diuresis. This accelerates microvascular

TE

complications.93
EP

NEUROLOGIC

Brain atrophy changes occur as a result of the malnutrition of anorexia nervosa.

C

Neurocognitive functioning may be permanently impaired even though brain atrophy

AC

improves with weight restoration.94 Both gray and white matter are affected.

DERMATOLOGIC
 ACCEPTED MANUSCRIPT

There are multiple skin changes that occur in anorexia nervosa. These include

xerosis, lanugo hair growth on the spine and sides of the face, thinning of the hair,

acrocyanosis and perinosis. Increased acne and carotenoderma have also been

described.95 None of these are signs of virilization, but rather are either related to

PT
reduced subcutaneous tissue or to the body’s attempt to maintain core temperature and

RI
prevent heat loss. They all resolve with weight gain.

SC
MEDICAL COMPLICATIONS OF BULIMIA

Self-Induced Vomiting

U
While the mortality rate associated with bulimia is much less than in anorexia
AN
nervosa, it is also elevated due to the severe electrolyte and acid base alterations which

can be associated with purging behaviors. Ninety percent of the purging behaviors
M

found in bulimia are either self-induced vomiting or the abuse of stimulant laxatives.
D

With self-induced vomiting, the complications can be divided into the local adverse
TE

effects of vomiting and the electrolyte-acid base abnormalities which can ensue as this

behavior becomes more extreme. Excessive vomiting can lead to persistent gastric
EP

acid reflux leading to dysphagia and dyspepsia. Treatment is cessation of this behavior

and the administration of proton pump inhibitors. Whether patients with bulimia should
C

be screened for Barrett’s esophagus is not clear.96 There have been reports of
AC

esophageal malignancy in bulimia.97 But, even screening for Barrett’s esophagus is the

general population with reflux has recently been questioned due to lack of proof of

efficicacy.98 Hematemesis is usually due to the limited Mallory-Weiss tears. Epistaxis

and subconjunctival hemorrhages are self-limited, but recurrent epistaxis in a young

 ACCEPTED MANUSCRIPT

female should raise the question of covert bulimia. Perimolysis refers to erosion of the

dentin and enamel on the lingual service of the teeth due to repeated exposure to

stomach acid.99 Similarly, oral mucositis and cheilitis are found in these patients from

the recurrent vomiting. Recommended therapies include oral hygiene such as gentle

PT
brushing and use of a fluoride mouthwash.100 Acid exposure also causes damage to

RI
the larynx with inflammatory changes to the vocal cords and a hoarse voice.101

Parotid gland enlargement, or sialadenosis, is a common feature of self-induced

SC
vomiting, although the precise mechanism remains elusive.102 Tissue examination of

these parotid glands reveals large acini with prominent zymogen granules without other

U
pathology. Of note, sialadenosis develops 3-4 days after the cessation of chronic
AN
excessive self-induced vomiting and can be very distressing to a patient with bulimia

whose focus on body image is exaggerated. The swelling is bilateral, with minimal
M

tenderness. There may be elevation of the salivary isonmylase enzyme serum level.103
D

Treatment should ideally be preemptive and comprised of use of sialagogues such as

TE

tart candies, along with an anti-inflammatory medication and the frequent application of

hot packs. Usually this will help prevent, or if started late, said treatment usually
EP

resolves the issue within 1-2 weeks. Rarely, oral pilocarpine may be judiciously used to

help resolve the sialadenosis.104

C

The most dangerous medical complications of self-induced vomiting relate to the

AC

acid-base and electrolyte changes which ensue as a result thereof. These aberrations

are the same which occur with abuse of diuretics as the preferred mode of purging, but

in general those encountered with self-induced vomiting are more profoundly abnormal.

The most common electrolyte abnormalities are a metabolic alkalosis and hypokalemia.
 ACCEPTED MANUSCRIPT

With vomiting this is due both to loss of acid and potassium in the vomitus, as well as

from the volume depleted state causing increased aldosterone secretion to sustain their

blood pressure. This course of compensatory events is referred to as pseudo-Bartter’s

syndrome.105 It predisposes these patients to a distressing propensity towards edema

PT
formation with the cessation of purging behaviors as well as if intravenous saline

RI
repletion is required and infused too quickly.106 These patients must be treated

differently than, for example, a patient with acute gastroenteritis in need of intravenous

SC
saline, in whom it can be safely infused rather quickly.107 While the protective elevated

aldosterone levels will self-normalize after a few weeks of no ongoing purging

U
behaviors, it is often purposeful to initiate spironolactone in a starting dose of 25-50 mg
AN
daily, to both prevent and treat edema formation. The finding of hypokalemia, in an

otherwise healthy young adult, is highly specific for the diagnosis of covert bulimia.108
M

The potentially severe degrees of hypokalemia and metabolic-alkalosis and resulting

D

cardiac arrhythmias which can develop in those who excessively purge, is the likely
TE

reason for the elevated mortality rate associated with bulimia nervosa.109 Recently,

hypokalemia was reported to be especially dangerous in females, which is the gender

EP

mostly identified to have bulimia.110

Most patients with bulimia nervosa use their fingers to provoke vomiting.
C

However, some abuse syrup of ipecac to accomplish this. This is even more dangerous
AC

because, emetine, the alkaloid in ipecac which induces vomiting, is a direct cardiac

toxin.111 This toxicity is cumulative. Each bottle of ipecac contains 30 mg of ementine

and with a dose of just 1,250 mg, there can be the development of an irreversible

cardiomyopathy and severe congestive health failure.112

 ACCEPTED MANUSCRIPT

Laxative Abuse

Excessive laxative abuse is the other main mode of purging.113 Hypokalemia is

again a potential risk of this behavior. However in contrast to diuretics and self-induced

PT
vomiting, laxative abuse is initially associated with a hyperchloremic metabolic acidosis

RI
which eventually reverts to a state of metabolic alkalosis after a chronic volume

depleted state evolves. In addition to the electrolyte abnormalities, laxative abuse

SC
causes expected local gastrointestinal adverse effects including rectal prolapse,

diarrhea, hemorrhoids and hematochezia.114,115 There has long been a debate whether

U
stimulant initiative cause colorectal cancer.116
AN
One final and major complication of laxative abuse is the cathartic colon

syndrome.117 For many years it has been known that stimulant laxatives, whose
M

mechanism of action is based on stimulation of peristalsis via a direct effect on

D

Auerbach’s plexus in the colon, can cause permanent harm to these nerve plexi.118 As a
TE

result of chronic usage, the colon is converted into an inert tube incapable of the

propagation of fecal material and severe constipation ensues,119 which may necessitate
EP

a colectomy. The exact amount of time or quantity of abuse needed to cause the

cathartic colon syndrome is unknown. Therefore it is important to exhort these patient

C

to cease abuse of laxatives which either contain senna, cascara, phenothalcin or

AC

bisocodyl. The aforementioned edema formation which can develop can also be

treated with spironolactone and patient concerns about resultant constipation can be

allayed with substitution of a judicious amount of an osmotic laxative.120,121 Much less

commonly patients with bulimia purge via the usage of enema type products.122 The
 ACCEPTED MANUSCRIPT

main dangers from them are attributable to the electrolyte abnormalities previously

mentioned, but also from the potential for fatal hyperphosphatemia from the sodium-

phosphate active ingredients.123

PT
CONCLUSION

RI
In summary, both anorexia nervosa and bulimia nervosa inherently have a litany

of medical complications associated with them. While most of them are treatable after

SC
effective medical interventions and psychotherapy. To halt the disease process, these

are a notable few which are associated with permanent harm. Therefore, given the

U
relatively young age of onset of these illnesses, there is an impelling need for informed
AN
medical treatment to help achieve a successful treatment outcome.
M
D
TE
C EP
AC
 ACCEPTED MANUSCRIPT

REFERENCES

1. Sullivan PF. Mortality in anorexia nervosa. Am J Psychiatry. 1995;152:1073-1074.

2. Harris EC, Barraclough B. Excess Mortality of Mental Disorder. Br J Psychiatry.

1999;173:11-53.

PT
3. Emborg C. Mortality and causes of death in eating disorders in Denmark 1970-1993:

RI
a case register study. Int J Eat Disord. 1999;25:243-251.

SC
4. Nielsen S. Epidemiology and mortality of eating disorders. Psychiatr Clin North Am.

2001;24:201-214.

U
5. Mehler PS, Krantz M. Anorexia nervosa medical issues. J Womens Health.
AN
2003;12:331-340.
M

6. Guarda AS. Treatment of anorexia nervosa: insights and obstacles. Physiol Behav.

2008;94:113-120.
D
TE

7. Herpertz-Dahlmann B. Adolescent eating disorders: definitions, symptomatology,

epidemiology and comorbidity. Child Adolesc Psychiatr Clin N Am. 2009;18:31-47.

EP

8. Crow SJ, Peterson CB, Swanson SA, et al: Increased Mortality in Bulimia Nervosa

and Other Eating Disorders. Am J Psychiatry. 2009;166:1342-1346.

C
AC

9. American Psychiatric Association, Diagnostic and Statistical Manual of Mental

Disorders, 338-45 (5th ed.). 2013.

10. Andersen A, Yager J. Eating disorders. In: Saddock BJ and Saddock VA. Kaplan

and Saddock’s Comprehensive Textbook of Psychiatry, 8th Edition. Philadelphia:

Lippincott, Williams and Wilkins. Pp. 2002-2021, 2005.

 ACCEPTED MANUSCRIPT

11. Lulé D, Schulze UME, Bauer K, et al. Anorexia nervosa and its relation to

depression, anxiety, alexithymia and emotional processing deficits. Eat Weight

Disord. 2014;19:209-216.

PT
12. Kaye WH, Fudge JL, Paulus M. New insight into symptoms and neurocircuit function

in anorexia nervosa. Nat Rev Neurosci. 2009;10:573-584.

RI
13. Zink CF, Weinberger DR. Cracking the moody brain: the rewards of self- starvation.

SC
Nat Med. 2010;16:1382-1383.

14. Pollice C, Kaye WH, Greeno CG, Weltzin TE. Relationship of depression, anxiety

U
and obsessionality to state of illness in anorexia nervosa. Int J Eat Disord.
AN
1997;21:367-376.
M

15. McAdams CJ, Krawczyk DC. Impaired neuronal processing of social attribution in

anorexia nervosa. Psych Res. 2011;194:57-63.

D

16. Neufang S, Specht K, Hausman M, et al. Sex differences and the impact of steroid
TE

hormones on the developing human brain. Cereb Cortex. 2009;19:464-473.

17. Rothemund Y, Buchald C, Georgiewa P, et al. Compulsivity predicts fronto striatal

EP

activation in severely anorectic individuals. Neurosci. 2011;197:242-25-.

18. Bühren K, Schwarte R, Fluck N, et al. Comorbid psychiatric disorders in female

C

adolescents with first-onset anorexia nervosa. Eur Eat Disorders Rev. 2013;22:39-
AC

44.

19. Aspen V, Weisman H, Nafiz N et al. Psychiatric comorbidity in women presenting

across the continuum of disordered eating. Eat Behav. 2014;15:686-693.

 ACCEPTED MANUSCRIPT

20. Hudson JL, Hiripi E, Pope HG, Jnr, Kessler RC. The prevalence and correlates of

Eating Disorders in the National Comorbidity Survey Replication. Biol Psych.

2007;61:348-358.

21. Swanson SA, Crow SJ, LeGrange D, et al. Prevalence and correlates of eating

PT
disorders in adolescents. Correlates from the national comorbidity survey.

RI
Replication adolescent survey. Arch Gen Psych. 2011;68:714-723.

22. Brown TA, Haedt-Matt AA, Keel PK. Personality pathology in purging disorder and

SC
bulimia nervosa. Int J Eat Disord. 2011;44:735-740.

U
23. Rossiter EM, Agras WS, Telch CF, Schneider JA. Cluster B personality disorder
AN
characteristics predict outcome in patients with bulimia nervosa. Int J Eat Disord.

1993;13:349-357.
M

24. Herzog TA, Hartmann A, Sandholz A, Stammer H. Prognostic factors in outpatient

D

therapy of bulimia. Psychother and Psychosomatics. 1991;56:48-55.

TE

25. Button EJ, Chadalavada B, Palmer RL. Mortality and predictors of death in a cohort

of patients presenting to an eating disorders service. Int J Eat Disord. 2010;43:387-

EP

392.
C

26. Franko DL, Keel PK, Dorer DJ, et al. What predicts suicide attempts in women with
AC

eating disorders? Psychol Med. 2004;34:843-853.

27. Keel PK, Dorer DJ, Eddy KT, et al. Predictors of Mortality in Eating Disorders. Arch

Gen Psychiatry. 2003;60:179-183.

 ACCEPTED MANUSCRIPT

28. Papadopoulos FC, Ekbom A, Brandt L, et al. Excess mortality, causes of death and

prognostic factors in anorexia nervosa. Br J Psychiatry. 2009;194:10-17.

29. Raykos BC, McEvoy PM, Carter O, Fursland A, Nathan P. Interpersonal problems

PT
across restrictive and binge-purge samples: data from a community-based eating

disorders clinic. Eat Behav. 2014;15:449-452.

RI
30. Atiye M, Miettunen J, Raevuori-Helkamaa A. A meta-analysis of temperament in

SC
eating disorders. Eur Eat Disord Rev. 2015;23:88-99.

31. Brauhardt A, de Zwaan M, Hilbert A. The therapeutic process in psychological

U
treatments for eating disorders: a systematic review. Int J Eat Disord 2014;47:565-
AN
584.
M

32. Yager J, Devlin MJ, Halmi KA, Herzog DB, Mitchell JE, Powers P, Zerbe KJ.

Practice guideline for the treatment of patients with eating disorders. 3rd ed.
D

Washington, DC: American Psychiatric Association. 2006.

TE

33. Kaye WH, Nagata T, Weltzin TE, et al. Double-blind placebo controlled
EP

administration of fluoxetine in restricting and purging type anorexia nervosa. Biol

Psych. 2001;49:644-652.
C

34. Walsh BT, Kaplan AS, Attia E, et al. Fluoxetine after weight restoration in anorexia
AC

nervosa: a randomized controlled trial. JAMA. 2006;295:2605-2612.

35. deVos J, Houtzager L, Katsaragaki G, et al. Meta-analysis on the efficacy of

pharmacotherapy versus placebo on anorexia nervosa. J Eat Disord. 2014;2:27.

 ACCEPTED MANUSCRIPT

36. Kaye WH, Frank GK, Bailer UF, Henry SE. Neurobiology of anorexia nervosa:

clinical implications of alterations of the function of serotonin and other neuronal

systems. Int J Eat Disord. 2005;37:S15-S19.

PT
37. Hay PJ, Claudino AM. Clinical psychopharmacology of eating disorders: a research

update. Int J Neuropsychopharmacol 2012; 15:209-222.

RI
38. Flament MF, Bissada H, Spettigue W. Evidence-based pharmacotherapy of eating

SC
disorders. In J Neuropsychopharmacol 2012;15:189-207.

39. McKnight RF, Park RJ. Atypical antipsychotics and eating disorders: a review. Eur

Eat Disord Rev 2010;18:10-21.

U
AN
40. Kishi T, Kafantaris, Sunday S, et al. Are antipsychotics effective for the treatment of
M

anorexia nervosa? Results from a systematic review and meta-analysis. J Clin

Psychiatry 2012;73:e757-e766.
D
TE

41. Goldstein DJ, Wilson MG, Ashcroft RC, et al. Effectiveness of pharmacotherapy in

bulimia nervosa regardless of comorbid depression. Int J Eat Disord 1999;25:19-27.

EP

42. Walsh BT, Agras WS, Devlin MJ, Fairburn CG, Wilson GT, Kahn C, Chally MK.

Fluoxetine for bulimia nervosa following poor response to psychotherapy. Am J

C

Psychiatry 2000;157:1332-1334.
AC

43. Serpell S, Stobie B, Fairburn CG, et al. Empirically-supported and non-empirically

supported therapies for bulimia nervosa: retrospective patient ratings. J Eat Disord

2013;1:41.
 ACCEPTED MANUSCRIPT

44. Gaudiani JL, Braverman JM, Mascolo M, Mehler PS. Lagophthalmos in severe

anorexia nervosa: a case study. Arch Ophthalmol. 2012;130:928-930. doi:

10.1001/archophthalmol.2011.2515.

45. Holmes SR, Gudridge TA, Gaudiani JL, Mehler PS. Dysphagia in severe anorexia

PT
nervosa: a case report. Int J Eat Disord. 2012;45:463-466. doi: 10.1002/eat.20971.

RI
46. Benini L, Todesco T, Dalle Grave R, Deiorio F, Salandini L, Vantini I. Gastric

emptying in patients with restricting and binge/purging subtypes of anorexia nervosa.

SC
Am J Gastroenterol. 2004;99:1448-1454.

47. Mascolo M, Dee E, Townsend R, Brinton JT, Mehler PS. Severe gastric dilatation

U
due to superior mesenteric artery syndrome in anorexia nervosa. Int J Eat Disord.
AN
2015 Jan 30. doi: 10.1002/eat.22385.

48. Welsch T, Buchler MW, Kienle P. Recalling superior mesenteric artery syndrome.
M

Dig Surg. 2007;24:149-156.

D

49. Le Moigne F, Lamboley JL, Vitry T, Stoltz A, Galoo E, Salamand P, Michel P,

TE

Farthouat P. Superior mesenteric artery syndrome: a rare etiology of upper intestinal

obstruction in adults. Gastroenterol Clin Biol. 2010;34:403-406. doi:

EP

10.1016/j.gcb.2010.04.012.

50. Zipfel S, Sammet I, Rapps N, Herzog W, Herpertz S, Martens U. Gastrointestinal

C

disturbances in eating disorders: a clinical and neurobiological aspects. Auton

AC

Neurosci. 2006;129:99-106.

51. Miller KK, Grinspoon SK, Ciampa J, Hier J, Herzog D, Klibanski A. Medical findings

in outpatients with anorexia nervosa. Arch Intern Med. 2005;165:561-566.

 ACCEPTED MANUSCRIPT

52. De Caprio C, Alfano A, Senatore I, Zarrella L, Pasanisi F, Contaldo F. Severe acute

liver damage in anorexia nervosa: two case reports. Nutrition. 2006;22:572-575.

53. Brown CA, Sabel AL, Gaudiani JL, Mehler PS. Predictors of hypophosphatemia

during refeeding of patients with severe anorexia nervosa. Int J Eat Disord. 2015 Apr

PT
2. doi: 10.1002/eat.22406.

RI
54. Narayanan V, Gaudiani JL, Harris RH, Mehler PS. Liver function test abnormalities

in anorexia nervosa – cause or effect. Int J Eat Disord. 2010;43:378-38.

SC
55. Arnette EN, Isner JM, Redwood DR, Kent KM, Baker WP, Ackerstein H, Roberts

WC. Coronary artery narrowing in coronary heart disease: a comparison of

U
cineangiographic and necropsy findings. Ann Intern Med. 1979;91;350-356.
AN
56. Yahalom M, Spitz M, Sandler L, Heno N, Roguin N, Turgeman Y. The significance of

bradycardia in anorexia nervosa. International Journal of Angiology. 2013:22:83-94.

M

57. Krantz MJ, Gaudianni J, Johnson V, Mehler PS. Exercise Electrocardiography

D

Extinguishes Persistent Junctional Rhythm in a Patient with Severe Anorexia

TE

Nervosa. Cardiology. 2011;120:217-220.

58. Kossaify A. Management of sinus node dysfunction with junctional escape rhythm in
EP

a case of anorexia nervosa. Turk Kardiyol Dern Ars. 2010;38:486-488.

59. Krantz MJ, Sabel A, Sagar U, Long CS, Barbey JT, White K, Gaudianni J, Mehler
C

PS. Factors Influencing QT prolongation in Hospitalized Patients with Severe

AC

Anorexia Nervosa. Gen Hosp Psychiatry. 2011;34:173-177.

60. Facchini M, Sala L, Malfatto G, Bragato R, Redaelli G, Invitti C. Low-K+ dependent

QT prolongation and risk for ventricular arrhythmia in anorexia nervosa. International

Journal of Cardiology. 2006;106:170-176.

 ACCEPTED MANUSCRIPT

61. Oflaz S1, Yucel B, Oz F, Sahin D, Ozturk N, Yaci O, Polat N, Gurdal A, Cizgici AY,

Dursun M, Oflaz H. Assessment of myocardial damage by cardiac MRI in patients

with anorexia nervosa. Int J Eat Disord. 2013;46:862-866.

62. Lamzabi I, Syed S, Reddy VB, Jain R, Harbhajanka A, Arunkumar P. Myocardial

PT
changes in a patient with anorexia nervosa: a case report and review of literature.

RI
Am J Clin Pathol. 2015;143:734-737.

63. Gardini GG, Boni E, Todisco P. Respiratory function in patients with anorexia

SC
nervosa. Chest. 2009;136:1356-1360.

64. Biffl W, Narayanan V, Gaudiani JL, Mehler PS. The management of pneumothorax

U
in patients with anorexia nervosa. Patient Saf Surg. 2010;4:1-4.
AN
65. Hutter G, Ganepola S, Hofmann WK. The hematology of anorexia nervosa. Int J Eat

Disord. 2009;42:293-300.
M

66. Muhajir M. Gelatinous transformation of bone marrow in a patient with anorexia

D

nervosa. Int J Hematol. 2013;97:157-158.

TE

67. Nova E, Samartin S, Gomez S, Morande G, Marcos A. The adaptive response of

the immune system to the particular malnutrition of eating disorders. Eur J Clin Nutr.
EP

2002;56:S34-37.

68. Brown RF, Bartrop R, Beaumont P, Birmingham CL. Bacterial infections in anorexia
C

nervosa: delayed recognition increases complication. Int J Eat Disord. 2005;37:261-

AC

265.

69. Sabel A, Gaudiani J, Statland B, Mehler PS. Hematological abnormalities in severe

anorexia nervosa. Ann Hematol. 2013;92:605-609.

 ACCEPTED MANUSCRIPT

70. Corbetta F, Tremolizzo L, Conti E, Ferrarese C, Neri F, Bomba M, Nacinovich R.

Paradoxical increase of plasma vitamin B12 and folates with disease severity in

anorexia nervosa. Int J Eat Disord. 2015;48:317-322.

71. Kraeft JJ, Uppot RN, Heffess Am. Imaging findings in anorexia nervosa. AJR Am J

PT
Roentgenol. 2013;200:328-334.

RI
72. Faje AT, Fazeli PK, Miller KK, et al. Fracture risk and areal bone mineral density in

adolescent females with anorexia nervosa. Int J Eat Disord. 2014;47:458-466.

SC
73. Vestergaard P, Emborg C, Stovving RK, Hagen C, Moseklide L, Brixen K. Fractures

in patients with anorexia nervosa – a nationwide register study. Int J Eat Disord.

2002;32:301-308.
U
AN
74. Miller KK, Lee EE, Lawson EA, et al. Determinants of skeletal loss and recovery in

anorexia nervosa. J Clin Endocrinol Metab. 2011;91:2931-2937.

M

75. Klibanski A, Biller BM, Schoenfeld DA, Herzog DB, Saxe VC. The effects of
D

estrogen administration on trabecular bone loss in young women with anorexia

TE

nervosa. J Clin Endocrinol Metab. 1995;80:898-904.

76. Stokosh GR, Friedman AJ, Wu SC, Kamin M. Effects of oral contraceptive on bone
EP

mineral density in adolescent females with anorexia nervosa. J Adolesc Health.

2006;39:819-827.
C

77. Golden NH, Lanzkowsky L, Schebendach J, Palestro CJ, Jacobson MS, Shenker IR.
AC

The effect of estrogen progestin treatment on bone density in anorexia nervosa. J

Pediatr Adolesc Gynecol. 2002;15:135-143.

 ACCEPTED MANUSCRIPT

78. Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, et al. Physiologic estrogen

replacement increases bone density in adolescent girls with anorexia nervosa. J

Bone Miner Res. 2011;26:2430-2438.

79. Mehler PS, Mackenzie TD. Treatment of osteopenia and osteoporosis in anorexia

PT
nervosa. A systematic review of the literature. Int J Eat Disord. 2009;42:195-201.

RI
80. Golden NH, Iglesias EA, Jacobson MS, et al. Alendronate for the treatment of

osteopenia in anorexia nervosa. J Clin Endocrinol Metab. 2005;90:3179-3184.

SC
81. Fazeli PK, Wang IS, Miller KK, et al. Teriparatide increases bone formation and

bone mineral density in adult women with anorexia nervosa. J Clin Endocrinol

Metab. 2014;99:1322-1329.
U
AN
82. Zaher S, LeBoff M, Lewiecki M. Denosumab for the treatment of osteoporosis.

Expert Opin Drug Metab Toxicol. 2015;11:461-470.

M

83. Mehler PS, Sabel AL, Watson T, Andersen AE. High risk of osteoporosis in male
D

patients with eating disorders. Int J Eat Disord. 2008;41:666-672.

TE

84. Devlin MJ, Walsh BT, Katz JL, et al. Hypothalamic-pituitary-gonadal function in

anorexia nervosa. Psychiatry Res. 1989;28:11-16.

EP

85. Miller KKm Grinspoon S, Gleysteen S. Preservation of neuroendocrine control of

reproductive function despite under nutrition. J Clin Endocrinol Metab.

C

2004;89:4434-4438.
AC

86. Golden NH, Jacobson MS, Schebendach J, et al. Presumption of menses in

anorexia nervosa. Adolesc Med. 1997;151:16-21.

 ACCEPTED MANUSCRIPT

87. Jocangeli F, Masala S, Staar Mezzasalma F, et al. Amenorrhea after weigh recovery

in anorexia nervosa: role of body composition and endocrine abnormalities. Eating

Weight Disorder. 2006;11:e20-26.

88. Lo Sauro C, Ravaldi C, Cabras PL, et al. Stress, hypothalamic-pituitary-adrenal axis

PT
and eating disorders. Neuropsychobiology. 2008;57:95-100.

RI
89. Golden NH, Kreitzer P, Jacobson MS, et al. Disturbance in growth hormone

secretion and action in adolescents with anorexia nervosa. J Pediatr. 1994;125:655-

SC
660.

90. Utiger RD. Altero thyroid function in non-thyroidal illness and surgery. To treat or not

U
to treat. N Engl J Med. 1995;333:1562-1567.
AN
91. Rich LM, Caine MR, Findling JW, Shader JL. Hypoglycemic coma in anorexia

nervosa. Arch Intern Med. 1990;150:894-898.

M

92. Baechle C, Castillo K, Strasburger K. Is disordered eating behavior more prevalent

D

in adolescents with type 1 diabetes then in their respective peers? Int J Eat Disord.
TE

2014;47:342-352.

93. Wisting L, Frossland DH, Skrivarhaug T, Dahl-Jorgenson K, Ro O. Disturbed eating

EP

behavior and commission of insulin in adolescents receiving insulin treatment.

Diabetes Care. 2013;36:3382-3387.

C

94. Roberto CA, Mayer LE, Brickman AM, et al. Brain tissue volume changes following
AC

weight gain in anorexia nervosa. Int J Eat Disord. 2011;44:406-410.

95. Strumia R, ed. Eating Disorders and the Skin. Springer Publishing Company: New

York. 2012.
 ACCEPTED MANUSCRIPT

96. Denholm M, Jankowski J. Gastroesophageal reflux disease and bulimia nervosa—A

review of the literature. Dis Esophagus. 2011;24:79–85. doi:10.1111/j.1442–

2050.2010.01096.

97. Dessureault S, Coppola D, Weitzner M, Powers P, Karl RC. Barrett’s esophagus and

PT
squamous cell carcinoma in a patient with psychogenic vomiting. Int J Gastrointest

RI
Cancer 2002;32:57–61.

98. Spechler SJ, Souza RF. Barrett’s Esophagus. N Engl J Med 2014;371:836-845. doi:

SC
10.1056/NEJMra1314704.

99. Uhlen MM, Tveit AB, Stenhagen KR, Mulic A. Self-induced vomiting and dental

U
erosion--a clinical study. BMC Oral Health 2014;14:92. doi: 10.1186/1472-6831-14-
AN
92.

100. Christensen GJ. Oral care for patients with bulimia. J Am Dent Assoc
M

2002;133:1689–1691.
D

101. Ferreira CP, Gama AC, Santos MA, Maia MO. Laryngeal and vocal analysis in
TE

bulimic patients. Braz J Otorhinolaryngol 2010;76:469-477.

102. Coleman H, Altini M, Nayler S, Richards A. Sialadenosis: a presenting sign in

EP

bulimia. Head Neck 1998;20:758-762.

103. Kinzl J, Biebl W, Herold M. Significance of vomiting for hyperamylasemiaand

C

sialadenosis in patients with eating disorders. Int J Eat Disord 1993;13:117–124.

AC

104. Mehler PS, Wallace JA. Sialadenosis in bulimia: A new treatment. Arch

Otolaryngol Head Neck Surg 1993;119:787–788.

105. Bahia A, Mascolo M, Gaudiani JL, Mehler PS. PseudoBartter syndrome in eating

disorders. Int J Eat Disord 2012;45:150-153. doi: 10.1002/eat.20906.

 ACCEPTED MANUSCRIPT

106. Trent SA, Moreira ME, Colwell CB, Mehler PS. ED management of patients with

eating disorders. Am J Emerg Med 2013;31:859-865. doi:

10.1016/j.ajem.2013.02.035.

107. Mascolo M, Trent S, Colwell C, Mehler P. What the emergency room department

PT
needs to know when caring for patients with eating disorders. Int J Eat Disord.

RI
2012;45:977-981.

108. Wolfe BE, Metzger ED, Levine JM, Jimerson DC. Laboratory screening for

SC
electrolyte abnormalities in bulimia nervosa. Int J Eat Disord. 2001;30:288-293.

109. Crow SJ, Peterson CB, Swanson SA, Raymond VC, Speeker S, et al. Increased

U
mortality in bulimia nervosa and other eating disorders. Am J Psychiatry.
AN
2009;166:1342-1346.

110. Jensen HK, Brabrand M, Vinholt PJ, Hallas J, Lassen AT. Hypokalemia in acute
M

medical patients: risk factors and prognosis. Am J Med 2015;128:60-67. doi:

D

10.1016/j.amjmed.2014.07.022.
TE

111. Silber TJ. Ipecac syrup abuse, morbidity, and mortality: isn't it time to repeal its

over-the-counter status? J Adolesc Health 2005;37:256-260.

EP

112. Ho PC, Dweik R, Cohen MC. Rapidly reversible cardiomyopathy associated with

chronic ipecac ingestion. Clin Cardiol 1998;21:780-783.

C

113. Koracs D, Palmer RL. The association between laxative abuse and other
AC

symptoms among adults with anorexia nervosa. Int J Eat Disord. 2004;36:224-

228.

114. Xing JH, Soffer EE. Adverse effects of laxatives. Dis Colon Rectum.

2001;44:1201-1209.
 ACCEPTED MANUSCRIPT

115. Malik M, Stratton J, Sweeney WB. Rectal prolapse associated with bulimia

nervosa: report of seven cases. Dis Colon Rectum 1997;40:1382-1385.

116. Dukas L, Willett WC, Colditz GA, Fuchs CS, Rosner B, Giovannucci EL.

Prospective study of bowel movement, laxative use, and risk of colorectal cancer

PT
among women. Am J Epidemiol 2000;151:958-964.

RI
117. Muller-Lissner S. What has happened to the cathartic colon? Gut 1996;39:486-

488.

SC
118. Smith B. Effect of irritant purgatives on the myenteric plexus in man and the

mouse. Gut 1968;9:139-143.

U
119. Joo JS, Ehrenpreis eD, Gonzalez L, Kaye M, Breno S, Wexner SD, Zaitman D,
AN
Secrest K. Alterations in colonic anatomy induced by chronic stimulant laxatives:

the cathartic colon revisited. J Clin Gastroenterol 1998;26:283-286.

M

120. Colton P, Woodside DB, Kaplan AS. Laxative withdrawal in eating disorders.
D

Treatment protocol and 3 to 20 year follow up. Int J Eat Disord 1997;25:311-317.
TE

121. Chu ES, Gaudiani JL, Mascolo M, Statland B, Sabel A, Carroll K, Mehler PS.

ACUTE center for eating disorders. J Hosp Med 2012;7:340-344. doi:

EP

10.1002/jhm.1906.

122. Davies C. The use of phosphate enemas in the treatment of constipation. Nurs
C

Times. 2004;100:32-35.
AC

123. Ori Y, Rozen-Zoi B, Chagnac A. Fatalities and severe metabolic disorders

associated with the use of sodium phosphate enemas. Arch Intern Med.

2012;172:263-265.
 ACCEPTED MANUSCRIPT

Clinical Significance

• Anorexia nervosa and bulimia have many medical complications associated with
them
• In anorexia nervosa the medical complications are due to weight loss and
malnutrition
• In bulimia the medical complications are due to the mode and frequency of purging

PT
• Most complications are reversible with early effective treatment

RI
U SC
AN
M
D
TE
C EP
AC