Obesity Flashcards
chronic condition defined as an excess of body fat or adipose tissue that causes disease.
Obesity
A normal BMI
18.5 and 24.9 kg/m2
overweight
BMI between 25 and 29.9 kg/m2
class I obesity
BMI of 30 to 34.9 kg/m2
class II obesity
BMI of 35 to 39.9 kg/m2
class III obesity
BMI greater than 40 kg/m2
Complications of obesity
type 2
diabetes, stroke, heart disease, NAFLD, and several types of
cancer, all of which are considered obesity-related causes of
preventable death globally
Dietary Factors
These studies favor a high-protein, low-carbohydrate diet for
avoidance of excess weight gain.
high-protein diets
may be favorable are increased satiety, increased thermic effect
of food, and improved body composition.
Medication-Induced Weight Gain
antipsychotics (e.g., olanzapine, clonazapine),
antidepressants (e.g., the SSRI, paroxetine), anti-epileptics (e.g., valproate, gabapentin), insulin and insulin secretagogues (e.g., thiazolidinediones),
glucocorticoids,
progestational hormones and implants,
oral contraceptives,
beta-blockers
Smoking
first, smoking is thermogenic—that is, the metabolic rate
during the act of smoking is higher than when the subject is not
smoking;
second, smoking reduces hunger and changes taste perception so smokers tend to eat less.
Genetics
The melanocortin-4 receptor (MC4R) gene, leptin gene, pro-opiomelanocortin (POMC) gene, and agouti gene all have significant effects on body fat and fat stores.
Obesity, mental retardation, brachymetaphalangism, short stature
Missense, frameshift, nonsense, splice-site, deletions, insertions in GNAS1/GNAS. Autosomal dominant
Albright hereditary osteodystrophy/ pseudohypoparathyroidism type Ia
Childhood obesity, insulin resistance and type 2 diabetes mellitus, blindness, hearing impairment
Frameshift, nonsense, missense in ALMS1. Autosomal recessive
Alström syndrome
Obesity, retinitis pigmentosa, renal malformation, polydactyly, mental retardation, hypogonadism
Missense, nonsense, splice-site and frame-shift mutations in BBS1, BBS2. Autosomal recessive
Bardet-Biedl syndrome/Laurence- Moon-Bardet-Biedl syndrome
Obesity, umbilical hernia, soft tissue syndactyly, congenital heart disease, mental retardation, hypogenitalism
Truncating, missense, nonsense mutations of RAB23. Autosomal recessive
Carpenter syndrome/ acrocephalopolysyndactyly type II
Obesity and hyperphagia, failure to thrive, hypotonia, genital hypoplasia, mental retardation, small hands and feet
Deletions, mutations, loss of paternal allele MKRN3/ ZNF127/MAGEL2. Autosomal dominant, x-linked
Prader-Willi syndrome/Prader- Labhart-Willi
Leptin
Absence of leptin or an ineffective leptin receptor is associated with severe obesity
Leptin has the dual effect of reducing food
intake and increasing energy expenditure, both of which favor
loss of body fat.
Treatment of leptin-deficient children with
leptin decreased their body weight and hunger, indicating
the importance of leptin in normal subjects.
PATHOPHYSIOLOGY OF OBESITY
One body of neurons expresses the orexigenic peptides neuropeptide Y and agouti-related peptide, each of which function to increase food intake and reduce energy expenditure.
express POMC, and cocaine- and amphetamine-regulated transcript, which are anorexigenic peptides that lead to a reduction in appetite and increase in energy expenditure by activation of downstream pathways, such as activation of MC4R in the para- ventricular nucleus of the hypothalamus.
Damage to POMC neurons
Damage to POMC neurons and concomitant inflammation has been associated with diet-induced obesity and resistance to weight-regulating hormones including leptin and insulin
reduce food intake
Intestinal peptides, including glucagon-like peptide (GLP),
CCK, pancreatic polypeptide, and polypeptide YY
stimulates food intake
ghrelin, a small peptide produced in the stomach
an enzyme that is activated or inhibited in relation to the ratio
of adenosine monophosphate to adenosine triphosphate and is
thought to be the underlying central point in the control system of food intake
Oxidation of fatty
acids modulates activity of 5′-adenosine monophosphate kinase
Waist circumference
Waist circumference should be measured with the proper technique at the level directly above the iliac crests, especially in patients with a BMI greater than 25 to 35 kg/m2 who will require further risk stratification
indicative of insulin resistance;
presence of acanthosis nigricans and skin tags
violaceous striae and dorsocervical fat pads indicative of hypercortisolism; and thyromegaly and delayed reflexes as signs of hypothyroidism.
Lipid Derangements
dyslipidemia, characterized by low HDL cholesterol and high
TG levels, is more common in obese than in non-obese individuals, particularly those with central adiposity.
Obesity also increases the risk of heart failure and atrial fibrillation
Obesity-related
glomerulopathy
a BMI ≥30 kg/m2 and the
presence of glomerulomegaly with or without focal segmental
glomerulosclerosis on kidney biopsy
Gallbladder Disease
increased total cholesterol levels
seen in patients with obesity are excreted in the bile, where high
cholesterol concentrations relative to bile acids and phospholipids may increase the likelihood of precipitation of cholesterol
gallstones in the gallbladder.
Gallbladder Disease
During weight loss, the likelihood
of gallstone formation paradoxically increases because the flux of
cholesterol mobilized from fat is increased throughout the biliary
system
Gastroesophageal Reflux Disease (GERD)
erosive esophagitis and esophageal adenocarcinoma were also more common in obesity, with prevalence rates of 12.5% for BMI less than 25 kg/m2 compared with 26.9% for BMI greater than 30 kg/m for erosive esophagitis
Cancer
Men with obesity have an increased risk for
colon, rectal, and prostate cancers
women with obesity experience more cancers of the reproductive system and
gallbladder
greater risk of endometrial cancer in overweight
women is the increased production of estrogens by aromatization in adipose tissue, which is related to the degree of excess
body fat and accounts for a major source of estrogen production in postmenopausal women.
Breast cancer
Breast cancer is not only
related to total body fat but may also have a more important
relationship to central body fat, which may help explain why
breast cancer risk is increased at age 75 in women in the highest quartile BMI. Increased visceral fat as measured by CT
shows an important relationship to the risk of breast cancer.
Obstructive Sleep Apnea
Increased neck circumference (≥17 inches in men and ≥16 in
women), enlarged floppy uvula, and tonsillar hypertrophy are
predictors of obstructive sleep apnea (OSA).
Acanthosis nigricans refers
to a deepening pigmentation in the folds of the neck, axillae,
knuckles, and extensor surfaces that occurs in many overweight
individuals
Low-Fat Diets (LFDs)
dietary guidelines recommend a reduction in the daily intake of fat to 30% of energy intake or less.
In a met-analysis of trials comparing LFDs (typically <25% of total calories from fat) with a control group consuming a regular diet (30% to 40% of total calories),
Low-Carbohydrate Diets (LCDs)
Paleo diet is a variation of an LCD as it removes grains, in addition to dairy, from the diet.
Pharmacotherapy
The National Heart, Lung, and Blood Institute of the National Institutes of Health recommends that for individuals who fail to respond to lifestyle interventions after 6 months of treatment, have a BMI of greater than 30 kg/m2, or a BMI of greater than 27 kg/m2 with a weight-induced comorbidity, weight-loss medication may be added to their treatment plan
Phentermine/Topiramate
Low-dose, controlled-release phentermine plus topiramate (as 1 capsule)
Phentermine is an adrenergic agonist that promotes weight loss by activation of the sympathetic nervous system with a subsequent decrease in food intake and increased resting energy expenditure
Lorcaserin
selective serotonin 2C receptor agonist, was approved by the FDA in 2012 as a long-term treatment for obesity.
selectively activates the central serotonin 2C receptor over the 2A and 2B receptors and reduces appetite by binding to the 5HT-2C receptors on anorexigenic POMC neurons in the hypothalamus.
The recommended dose of lorcaserin is 10 mg twice daily with or without food. There is also a new 20 mg extended release tablet to be taken once daily.
Bupropion/Naltrexone
Bupropion’s primary mechanism of action is as a reuptake inhibitor of dopamine and norepinephrine.
Inhibiting reuptake of dopamine and/or norepinephrine modulates the “reward pathway” that various foods can stimulate.
Naltrexone is a pure opioid antagonist that blocks an opioid pathway that may slow weight loss.
Orlistat
inhibiting GI lipases, thereby decreasing the absorption of fat from the GI tract.
EVALUATION AND SELECTION OF BARIATRIC
SURGERY CANDIDATES
a BMI of 40 kg/ m2 or greater or a BMI of 35 kg/m2 or greater with obesity- related co-morbidities and at least 6 months of documented medically supervised weight loss attempts.
Contraindications to bariatric surgery
psychiatric conditions such as schizophrenia, severe bipolar disorder, active substance abuse, recent major depression with hospitalization or suicide attempts, and developmental delay.
Age is not an absolute contraindication in patients with severe co-morbidities and bariatric surgery is performed in patients older than age 65 or younger than age 18
recommended by the European Association for Endoscopic Surgery
A preoperative EGD is recommended by the European Association for Endoscopic Surgery to detect and treat any upper GI lesions that may cause postoperative complications or influence the decision of which type of bariatric surgery should be performed
Gastric Bypass
There are many variations of laparoscopic RYGB techniques, but essential components include construction of a gastric pouch, attaching the pouch to the jejunum, and re-routing digestive enzymes such that they do not contact food until it reaches the jejunojejunostomy
Prophylactic subcutaneous heparin (5000 units), sequential compression devices, and cefoxitin (2 g IV) should be administered prior to incision
Gastric Bypass
The greater omentum is elevated, and the ligament of Treitz is identified.
The jejunum is divided into biliopancreatic and Roux limbs at 20 cm distal to the ligament of Treitz.
Next, the jejunojejunostomy is performed after a 75 to 150 cm Roux limb is passed toward the proximal gastric pouch, either through the transverse mesocolon (retrocolic) or in front of the colon (antecolic); the retrocolic method may either take a retrogastric or antegastric route.
Any mesenteric defects between loops of bowel are potential hernia sites and, therefore, are closed with permanent running suture.
The gastric pouch should be between 15 mL and 30 mL in size and is constructed based on the size of the lesser gastric curve. Finally, the gastrojejunostomy is constructed either through circular-stapled, linear-stapled, or hand- sewn techniques, and a surgical drain may be placed.
Sleeve Gastrectomy
removing about 80% of the stomach, with a resultant remain- ing sleeve that is lesser curve-based and is 28 to 32 French (Fr) in diameter.
The patient is given a PPI for 6 months postoperatively as well as multivitamins to be taken for life.
Diet is slowly advanced over 8 weeks as an outpatient from full liquids to pureed food to soft food and finally to a regular diet.
Complications
Complications can be divided into 3 categories: intraoperative, early postoperative (within 30 days of surgery), and late postoperative (>30 days after surgery).
Early postoperative complications
Early postoperative complications are anastomotic leaks, pulmonary and cardiovascular complications including DVT and PE, and mortality.
Late postoperative complications
Late postoperative complications include anastomotic stricture, gallstone formation, nutritional deficiencies, bowel obstruction, intussusception, marginal ulcers or ulcers in the remnant stomach and duodenum, fistula, dumping syndrome, and hypoglycemia.
Cholelithiasis develops in up to 38% of patients after RYGB.
Gallstone formation
Gallstone formation occurs secondary to a combination of vagus nerve damage, altered enteric nerve stimulation, decreased gallbladder emptying, and changes in calcium concentration and the bile salt/ cholesterol ratio
To reduce the incidence of cholelithiasis, a 6-month course of ursodiol is recommended for patients whose gallbladder is not removed prophylactically.
Early dumping
Early dumping ensues 15 to 30 minutes after eating and is thought to be due to the rapid entry of hyperosmotic foods into the jejunum.
It is due to rapid fluid shifts into the intestinal lumen with a meal which results in a parasympathetic response leading to a reduction in systemic vascular resistance, an effect called “splanchnic blood pooling.”
Symptoms include cramping abdominal pain, voluminous diarrhea, bloating, dizziness, nausea, flushing, and tachycardia; symptoms result from hypovolemia and a subsequent sympathetic response.
is triggered by consumption of simple sugars, acidic foods, and nutrient-rich drinks such as Gatorade
Dumping syndrome
Early dumping is usually self-limited and resolves between 7 and 12 weeks after surgery.
Late dumping syndrome occurs 2 to 3 hours after a meal and is secondary to rapid glucose absorption, subsequent hyperglycemia, and release of glucagon-like peptide-1 and gastric inhibitory polypeptide.
Nutritional Deficiencies
patients who do not take daily vitamins postoperatively or patients who experience frequent vomiting are at increased risk of developing such deficiencies, most common of which are protein, iron, vitamin B12, folate, calcium, and the fat-soluble vitamins A, D, E, and K.
Nutritional Deficiencies
The parietal cells of the stomach produce intrinsic factor (IF), which is necessary for vitamin B12 absorption in the terminal ileum
Calcium, iron, and folate deficiency can occur because they
are absorbed mainly in the duodenum and proximal jejunum.
Patients who undergo RYGB
Patients who undergo RYGB may develop B12 deficiency because RYGB separates the parietal cells in the fundus of the stomach from the smaller gastric pouch.
Ulceration
Ulceration at the gastrojejunal anastomosis (GJA) is a common late complication of RYGB.
GJA ulceration often develops in the first 3 months postoperatively but can occur at any time.
Anastomotic ulcers may be due to small amounts of acid produced by the gastric pouch, ischemia, bile acid reflux, Hp infection, NSAIDs, smoking, alcohol, foreign bodies such as non- absorbable sutures or staples, or tension on the Roux lim
Treatment of Ulceration
In patients with
RYGB, anastomotic ulcers should be treated with soluble PPI
or capsules that are broken open, taken twice daily, and tapered
over 6 months.
Sucralfate solution at 1 g 4 times daily should
be used concurrently when possible; the tablet form of PPI does
not appear to be as effective. Bile reflux can be treated with bile
acid binders such as cholestyramine or colestipol. Smoking cessation is critical.
stenosis
stomal stenosis is present if the standard 9.5 mm endoscope cannot traverse the anastomosis.
Treatment of stomal stenosis can be performed with a through- the-scope (TTS) balloon, Savary dilator, or electrosurgical incision. Balloon dilation is the most commonly used technique and is successful in more than 90% of cases.
The balloon catheter should be advanced beyond the GJA, with care to avoid entry into the blind limb; a guidewire and/or fluoroscopic imaging can be used when observation of catheter advancement is sub-optimal, or resistance is encountered.
