CHAPTER A Practical Approach to Loss of

34 Dwijen Das, Tirthankar Roy

ABSTRACT overgrowth.1 Long lasting usually occurs only Appetite is the desire to eat , sometimes due to in people with serious and chronic underlying disorder. . Decreased desire to eat is termed as anorexia. A Disorders that affect the part of where appetite is brief period of anorexia usually accompanies almost all regulated can cause anorexia as well. In addition, the acute illnesses. Long lasting anorexia usually occurs only anorexia- syndrome is multifactorial and may in people with serious and chronic underlying disorder. involve chronic , depression or anxiety, hypogeusia plays a central role for maintaining the and hyposmia, chronic nausea, early satiety, malfunction appetite along with different neuropeptides. Loss of of the GIT and metabolic alterations.1,2 Unexplained appetite in acute illness is a sort of acute phase response chronic anorexia is a signal to the doctor that something is causes of which may vary from benign viral or bacterial wrong. A thorough evaluation of the person’s symptoms infection or drug induced to very serious lethal conditions and a complete physical examination often suggest a cause like chronic liver or kidney disease, carcinoma stomach and help the physician decide which tests are needed. and colon. PATHOPHYSIOLOGY Detailed clinical history and physical examination usually Feeding and Satiety suffice to pinpoint the cause but in certain situationsa Body weight depends on the balance between intake more aggressive approach with a battery of investigations and utilization of the calories. is usually the may be needed to diagnosethe exact cause of anorexia. result of reduced energy intake, not increased energy Detailed and extensive investigations in anorexia of expenditure. Reduced energy intake arises from dieting, shorter duration is usually unnecessary. Change in the loss of appetite, malabsorption or .3 Food pattern of meals served and change of environment intake is regulated not only on a meal to meal basis but can change appetite in certain cases. Therapy may be also in a way that generally maintains a given set point, required according to the underlying disease causing for example if animals are starved and then permitted to anorexia. eat freely, their spontaneous food intake increases until INTRODUCTION they regain the lost weight. Similarly, during recovery from illness, food intake is increased in a catch up fashion Our survival depends on the ability to procure food for until lost weight is regained.3 immediate metabolic needs and to store excess energy in the form of fat to meet metabolic demands during fasting. Role of the Hypothalamus3 Eating behaviour is stimulated by hunger, craving Appetite and are regulated by an intricate and hedonic sensations and controlled by homeostatic network of neural and hormonal factors. Regulation of processes. Appetite is the desire to eat food, sometimes appetite depends primarily on the interaction of two areas: due to hunger. Appealing can stimulate appetite a lateral hypothalamus “feeding center” in the nucleus of even when hunger is absent. Appetite exists in all higher the medial forebrain bundle at its junction with the pallido- life-forms, and serves to regulate adequate energy intake hypothalamic fibres, and the ventromedial hypothalamus to maintain metabolic needs. It is regulated by close “satiety centre” in the ventromedial nucleus. Stimulation interplay between the digestive tract, and of the feeding centre evokes eating behaviour in conscious the brain. individuals, and its destruction causes severe, fatal Decreased desire to eat is termed as anorexia, while anorexia in otherwise healthy individuals. Stimulation of (or hyperphagia) is increased eating. satiety centre causes cessation of eating, whereas lesion Dysregulation of appetite contributes to , in this region causes hyperphagia and, if the food supply , cachexia, and . is abundant, the syndrome of hypothalamic . Destruction of feeding centre with lesion of the satiety Loss of appetite implies that hunger is absent- a person centre causes anorexia, which indicates that, the satiety with anorexia has no desire to eat. A brief period of anorexia centre functions by inhibiting the feeding centre. Hence, usually accompanies almost all acute illnesses. Anorexia it appears that the feeding centre is chronically active and during disease can be beneficial or deleterious depending that its activity is transiently inhibited by activity in the on the timing and duration. Temporary anorexia during satiety centre after ingestion of the food. acute disease may be beneficial, since restriction of intake of micro- and macronutrients will inhibit bacterial Neuropeptides such as corticotrophin releasing hormone GASTROENTEROLOGY 182 by fattyacidsynthase. produced from Acetyl-CoA and is converted to fatty acids CoA in thetissue inhibits food intake. This substance is important observation isthataccumulationofmalonyl- adipose tissue, stimulates appetite. of loss the with conjunction in occurs which deficiency, and metabolism. behaviour food seeking alter that leptin activates aseriesofdownstreamneuralpathways the expression of α-MSH, which decreases appetite. Thus, expression ofhypothalamicneuropeptideYandincreases and increaseenergyexpenditure. by actingonthehypothalamustodecrease food intake long termmaintenanceofweightrole inthe It isproduced byadiposetissue,anditplaysacentral Leptin iv. iii. ii. mechanisms i. afferent about hypotheses involved inthecontroloffoodintakeare: main Four Afferent Mechanisms in thereceptorcausesnarcolepsy. because mutation hypothalamus. Theyarealsoofinterest They aresynthesizedintheneuronslocatedlateral that increase food intake include -A andOrexin-B. resulting inincreasedfoodintake.Otherpolypeptides exerts itsactionthroughY5receptorinthehypothalamus Y,is Neuropeptide polypeptide important One which induce anorexiabyactingcentrallyonsatietycentres. (α-MSH), hormone and amphetamine relatedtranscript(CART) stimulating melanocyte α- (CRH), decrease food intake. Hypoglycemia suppresses insulin, somatostatin and cholecystokininsignal satietyandthus The gastrointestinal peptides ,glucagon, of effect leptin. the blocks enzyme this of inhibition and cells, phosphotidylinisitol-3-hydroxykinase in hypothalamic by CB1blockade.Leptin activates theenzyme (2-AG). Theanorexiantaction ofleptinisantagonised 2-arachidonoglycerol and anadamide neurotransmitter nervous sytem.Itisactivated bytheendocannabinoid receptor located primarily inthecentraland peripheral as CB1,isaGprotein-coupledcannabinoid abbreviated 1, often CB1 receptors.Thecannabinoidreceptortype in thebodyincreasesappetitebyanactionon their active form of marijuana () that arefound rise above thesetpointinhibitsappetite. below agiven setpointstimulatesappetiteanda Thermostatic hypothesis: Fallinbodytemperature satiety. in thehypothalamusand produces a sensation of Glucostatichypothesis: Increase glucose utilization that actonthehypothalamustoinhibitfood intake. GIT causesthereleaseofoneormorepolypeptides Gut peptidehypothesis:Postulatesthatfood in the food intakeandincreaseenergyoutput. of fatandactsonthehypothalamustodecrease amount to the is proportionate humoral signalthat Lipostatic hypothesis: Adipose tissue produces a 3,5

4 Leptinsuppresses 5 A physiologically A 3,4 A potentially A 4 psychological andsocialfactors. visual, olfactoryandgustatorystimuliaswell asgenetic, of variety wide a by influenced be may intake Food loss. in decreased food intake) is directly relatedtoweight food energy requirements.Hencelossofappetite(resulting decreased includes loss intake, malabsorption,loss of calories and increased weight of Mechanism blood brainbarrier. directly byspecialized transport mechanisms through the stores. They can also signal thecentral nervous system Cytokines causes increased production of leptinfrom fat cytokines. pro-inflammatory of variety a of production walls, bacterialDNAandglycoproteins,whichcantrigger lipopolysaccharides, a peptidoglycanfrombacterialcell Response (APR)toit.The by triggered APR canbe Anorexia ininfectionisapartofthe Acute Phase 4. 3. 2. 1. • 4. 3. 2. 1. Hypothyroidism • ------• and inflammatory responses and induce a variety of avariety induce specificmetabolic alterations. and responses inflammatory and , depressmyocardialfunction,modulateimmune addition tocausinganorexia,thesefactorsmaystimulate Leukaemia inhibitoryfactor(LIF),caninducecachexia.In centre. and varietyIFNγ A TNFα, including cytokines, of the satiety reducing glucoseutilizationandinhibiting ETIOLOGY OF ANOREXIA Pernicious anemia Obstruction Malabsorption Acid pepticdisorder Gastrointestinal disorders Pheochromocytoma Adrenal insufficiency Diabetes mellitus Endocrine andmetabolic intestines. chemotherapy, gastrointestinal organs,suchas the stomach or Radiation treatmentorsurgerytoanypartofthe including cause feelingsofcalmnessorsleepiness. immunotherapy, anddrugscalledsedatives that Medications, eating asmallamountoffood. Ascites, may create a feeling of fullness even after the stomach,creatingafeelingoffullness. When aspleengrowsinsize,itcanpushon larger. Some cancers may causethespleentobecome Advanced cancer usually byaffectingaperson’smetabolism. and stomach cancers–may cause a loss of appetite, Some typesofcancer–includingovarian, pancreatic Cancer : 4 6 5,6 CHAPTER 34 183

, LFT, LFT, ,

Warning sign Treat according Treat according to etiology Significant wt Significant loss present indicated CBC, S. CreatCBC, Blood sugar, CRP,Stool for occult blood,HIV testing, imaging,Chest USG Abdomen, UGI Endoscopy, Colonoscopy as Maligancy, Chronic liver disease, Diabetes mellitus, HIV CKD, infection etc.

Long duration Long Parasitic infection Parasitic Subacute bacterial endocarditis Medications Dexmethylphenidate reuptake inhibitors Selective Topiramate and cocaine nicotine Stimulants such as caffeine, of appetite increasing drugs like Abrupt cessation corticosteroids and . Opiates, NSAIDS. teeth Disorders of mouth and Age related factors


Normal physical examination To be treated accordingly 1. HIV 2. 3. 4. • 1. Amphetamine 2. 3. 4. 5. 6. 7. • • Wait and observe for 6 months. No recovery indicates evaluation Rule outRule IBS, APD, early CKD, early CLD, psychiatric disorder S. Creat,CBC, LFT, Blood sugar, CRP, Abdomen,USG UGI No significant wt No significant loss

Loss of appetite Loss of

No Fever Apigastric ... APD Icterus.. Hepatitis, fatty liver H/o drug intake S. Bilirubin and fraction, ALT, markers,viral endoscopyUGI APD, Hepatitis, Fatty Drug liver, induced etc.

Fig. 1: Algorithmic approach to loss of appetite to 1: Algorithmic approach Fig.

dyspepsia accordingly

Short duration Short (Usually benign) H/o nausea, pain abdomen or


Treat Infection, infection UTI etc with Fever chills jaundice.. cholangitis, Dysuria... UTI Look signs for appendicitis, of cholecystitis UrineCBC, RE,CRP, USG abdomen, serological markers for specific Fever present Fever - Cholecystitis, cholangitis, Appendicitis, Pancreatic disorders Pancreatic Hepatic disorders disease Chronic liver hepatitis Viral Biliary disorders of pregnancy Acute fatty liver Cardiac disorders Chronic ischemia heart failure Congestive Respiratory disorders pulmonary disease Chronic obstructive Renal insufficiency Rheumatologic disease • 1. 2. 3. 4. • 1. 2. • 1. • • • Infections 5. GASTROENTEROLOGY 184 7. 6. 5. Alcoholism 4. Bereavement 3. 2. Anxiety 1. Depression • Psychiatric 2. 1. Isolation • Social 4. 3. Parkinsonism 2. Dementia 1. Stroke • Neurologic 2. 1. nervosa. Physicalexamination may reveal bilateral amenorrhea are some of thesymptoms of bulimia vomiting, dysphagia, bloating,constipation and self induced abdominal painwith irritation, headedness, palpitation, dryskin,pharyngeal least once weekly for3months. Dizziness, light occur at eating that require episodesofbinge criteria diagnostic DSM-5 hormone). thyroid (eg. use ofmedicationsintended tospeedmetabolism to useinsulininthosewithtypeIdiabetes,and/or diuretic abuse,useofappetitesuppressants,failure or compulsive,or strictdieting, episodesoffasting exercise generallyexperiencedas being joyless and/ self-induced vomiting,laxative abuse,excessive used byindividuals with bulimianervosainclude eating duringthis time. Compensatory behaviours behaviour is associated with a perceived loss of control of This period. defined same the during is significantly larger than is typical for most people period oftime(eg2hours)anamountfood that loss of control.Bingeeatingisinadiscrete associated with emotional distress and of eating episodes ofbinge characterized byfrequent Bulimia nervosa is typeofbingeeatingbehaviour Smoking (heavy) needs. amount that is well belowtheirbody’s caloric consumed, characteristically ingestingaminimal offood quantity the limit fiercely will individual exercising. In restrictive anorexia nervosa- the abusing laxativesvomiting, by orexcessively sufferer the guilt experiences inrelationtoeating;theycompensate of feelings overwhelming the a resultof when heorsheeats.Thisistypically purge will disorder this from suffering individual type- The nervosa: anorexianervosabinge/purge Anorexia Nervosa:Therearetwotypesofanorexia Economic hardship Neuromuscular disorders Decreased tasteandsmell Physiologic changes HIV infectionshouldbesoughtfor. and surgeryaswell asdiseases in thefamily. Risks for patient should be questionedaboutthepreviousillness reviewedmedications shouldbe and allthe andthe cigarettes and alcohol of use history, Travel for. sought nausea andvomiting,changeinbowel habitsshouldbe disturbances, includingdysphagia, Gastrointestinal breath, palpitationsand evidence of neurological diseases. associated with prolongedanorexia. medical disorders, medications, psychiatric disorders are oral disorders, major surgery, etc.Chronicunderlying onset anorexia is mainly associated with infections, is ofacuteonsetorchronic. it history, whether the Acute from anorexia of duration the access to is step first The fluctuations in weight and whether weight lossis weight and whether past progressive or stabilized. weight including anorexia, in of fluctuations pattern and duration the As partofthehistoryitisimportanttodetermine anorexia. that are associated with disorders that commonly cause The review of system should focus on sometime indicatesGImalignancy. of anorexiainourcountryandalsoenlargednecknodes for enlargedlymphnodes,astuberculosisisamajorcause should look considered. One must be patient status ofthe status should be looked for, and the social and economic lump should beperformed.Properpsychiatricandbehavioural abdominal and fluid free distension, tenderness, and calluses). Abdominal examinationtoaccess of bulimia(e.g.loss of teeth,enamel,knuckleulcerations of theindividualtoaccesssignswasting,fever, features 6. 5. 4. 3. 2. 1. anorexia: Following questionsshouldbeanswered inacaseof diseases. elderly maybeawarning featureofunderlyingmalignant New onsetanorexia ordyspepsiain age ofthepatient. weight,and physical activity decreased caloric intake, up. Otherfactorstoconsider, include intentiontolose are moreworrisomeandrequireimmediatefollow- presented withhistoryofweight loss that is progressive, weight hasbeenstableformanyyears andwho has APPROACH TOPATIENT THE (FIGURE1) obesity. andhypotension,edema and clinical self induced trauma, bradycardia, tachycardia, other and burning cutting, from resulting scarring hair loss,acne,dryskin,naildystrophyand diffuse sudden caries, dental enlargement, parotid Is thedecreased appetiteanewsymptom? How muchweight hasbeenlost? Is thefamilyworriedabout theeatinghabits? by thesymptoms? Is thepatienttroubled Is itsecondarytoothersymptoms (e.g.,nausea)? Is adiseaseprocesscausing thesymptoms? 8 These include fever, cough,pain,shortness of 8 Anorexia in a person whose 7 9 7 Properexamination CHAPTER 34 185 12 11 12 13 12 Try eating a bedtime snack. Try eating a bedtime 11,13 12 Between meals, sips of drinks with high calories with drinks sips of meals, Between 12 13 If care has been taken for someone with cancer, try not to with cancer, someone taken for been care has If eating. blame them for not Do not bribe or threaten them to get them to eat. Physicians may prescribe drugs to stimulate appetite in (Megace) megestrol include may drugs These cases. some or corticosteroids (steroids). Some people claim that marijuana helps increase their shown for certain, that appetite. To date, studies haven’t appetite. improve marijuana can effectively The management of anorexia depends but are include, Treatment strategies underlying cause. on the specific not limited to, pharmacologic therapy (eg, infections, Keep healthy, high-protein, high-calorie snacks available Keep healthy, high-protein, high-calorie snacks available patient’s appetite returns. they are ready to eat when so Eat food high protein in calories and when the appetite is poor. These foods include fish, chicken, turkey, eggs, Add lentils. beans and yogurt, cream, milk, ice cheese, and fat add to rice and cereal cooked vegetables, to butter calories. products. milk content of calorie the protein and Increase Double the protein and calorie content of whole milk by adding powdered dry milk. in fresh before meals, walking or doing light exercise Try air if possible. Increased activity just before eating and fresh air both stimulate the appetite. Eating atmosphere should be pleasant and relaxed, preferably with friends and family members whenever possible. Eating with someone else from food and can increase the amount consumed. distracts attention Keep mealtimes and snacks flexible and snacks mealtimes Keep appetite. the affect further can eating not about Worrying It is better to include variety to choice of the patient. according in served food and food even regularly eat to effort an Make meals. skip to not Try snacks and meals frequent bites. Small few only a is it if may have people Some the day are advised. throughout a better appetite in the morning, better to advice a large breakfast in them. and fun meals appealing Make Appetite is very much affected by how food looksin an An appealing food by the eating environment. and that what the trick. Recognize may do atmosphere of fun may not be the same the next day. is appealing one day every calorieMake count loss by increasing weight should advice to prevent We especially with of the food served, the nutritional value calories and protein. wants. the person and whenever Allow to eat whatever 1–2 hours throughout the Small snacks and meals every when the times during option. Eat well preferred a is day appetite returns. and protein are advisable. Add sugar syrup, honey or Add and protein are advisable. add to rolls and waffles cereals, meats, vegetables, to jelly calories. 10 As organic 9 10 It should start with It should 10 12 On follow-up, careful attention should attention careful follow-up, On 11 In observational studies, abnormal physical studies, In observational 9,10 Indian Gooseberry (amla) Ginger Black Pepper Cardamom (elaichi) Carom Seeds (ajwain) Diagnostic imaging: Chest radiograph. and If a GI cause is suspected, endoscopy colonoscopy with biopsies may be helpful. Laboratory testing: Complete blood count with Laboratory testing: Complete blood differential, chemistries thyroid renal and hepatic function, calcium, (electrolytes, glucose, urinalysis, stimulating hormone), hemoglobinA1c, erythrocyte sedimentation and hemoccult, stool protein (CRP). rate (ESR) or C-reactive If so, did it start after an upsetting event, such as friend? or family member of a the death TREATMENT disease is rarely found in patients with a normal physical examination and initial diagnostic testing, a waiting period of one to six months is unlikely to result in an outcome. adverse weight signs. of vital and documentation determination weight appearance, the overall should assess The clinician prior surgery, from turgors, scar skin changes (eg. other stigmata of angiomata and spider or melanoma thyroid gland dental diseases, or thrush disorders),oral lymphadenopathy, pallor, of enlargement, presence status, hepatosplenomegaly, icterus, cardiopulmonary breast/prostate abdominal mass, abnormalities, rectal examination with stool hemoccult, and any neurologic deficit. findings were common among those with malignancy. were findings 2. 3. 4. 5. Home remedies for loss of appetite for remedies Home 1. 2. 3. scanning in the initial workup, do not recommend CT We based on history or although CT scan may be indicated on based be should physical examination. Further studies an appropriate results of these initial tests. Despite initial not found. a clear cause for anorexia is often evaluation, preferable to a is six months to one for waiting Watchful battery of testing with low diagnostic yield. Diagnostic testing In patients with positive findings on history or physical on be focused examination, further testing should and history the When diagnosis. suspected the confirming a a likely diagnosis, physical examination do not indicate should include: basic diagnostic evaluation 1. Physical examination Several prospective studies have verified the importance anorexia in evaluating physical examination of a complete loss. unexplained weight and the 7. be paid to dietary history, possibility of psychosocial to dietary history, possibility of be paid causes, surreptitious drug intake, and new manifestations of occult illness. GASTROENTEROLOGY 186 3. 2. 1. treatment forundesired weight loss. recommended as analternative orcomplementary sex hasbeen EPA) or female acid (eicosapentaenoic oil fish the drugs, of derivative hormone .Inadditiontotheseprescription synthetic a (Megace), the malesexhormonetestosterone;andmegestrolacetate and ,whichareanabolicsteroidsrelatedto (marinol, THC),anantiemetic;nandrolone,oxymetholone, (Periactin), anantihistamine;dronabinol (Remeron),atetracyclicantidepressant; medications mostoftenusedintheearly2000sinclude and/or nutritionalsupport(eg,dementia,dysphagia).The depression, anorexianervosa) (eg, therapy behavioral endocrinopathies), surgery/radiation(eg,malignancy), 4. REFERENCES In: Reviewofmedicalphysiology;23r Ganong William F.Centralregulationofvisceralfunction. Elsevier; 2011:chap221. AI, eds. CecilMedicine.24thed.Philadelphia,Pa: Saunders Bistrian BR. Nutritional assessment. In: Goldman L, Schafer nutritional frailtyintheelderly.AnnuRevNutr2002;22:309. Bales CW, RitchieCS.Sarcopenia,weight loss,and Medicine; 17 Refie Carol M. Weight loss. Harrison’s Principles of Internal Graw-Hill, 2010;235-240. th edition;Chap41;255-256. d dto, S, Mc USA, edition, 13. 12. 11. 10. 9. 8. 7. 6. 5. cin , te C Bwa A Ivsiain and Investigation A. Bowman BMJ 2011;342:d1732. C, Steel management of unintentional weight loss in older adults. J, McMinn on=on#ixzz4EokLIlgq. and-treatment/managing-side-effects/loss-of-appetite/?regi Geriatrics 1989;44:31. Robbins LJ. Evaluation of weight loss in the elderly. 2008; 19:345. evaluationMed provideadequatereassurance?EurJIntern S. Involuntaryweight loss. Does anegative baseline Vanderschueren H, Bobbaers DC, Knockaert C, Metalidis 2012, Chap72;571-580. Principles of Internal Medicine; 18th edition; Mc Graw-Hill, Sudenski S, Ferruci L. Clinical problems of aging; Harrison’s 1981; 95:568. significance. prognostic and diagnostic loss: weight Involuntary JR. Krupp JR, HC Sox KI, Marton Elsevier Saunders,2015,Chap132;850-866. York,New edition; 25th Medicine; Goldman-Cecil disease; Gastrointestinal with patient the to Approach K. Mcquaid Saunders, 2015,Chap3;p9-14. Goldman-Cecil Medicine; 25 Medicine; Goldman-Cecil and theirfamilies. Arnold R.Careofdyingpatients 51:213. survival innursinghome residents. 1-year and factors Mortality-related DK. Kiely JM, Flacker th edition;NewYork, Elsevier J Am GeriatrSoc Ann InternMed 2003;