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BY

R.MADHURIPHARM-D ,II YEARROLL NO:05

OBESITY

•DEFINITION•ETIOLOGY•PATHOPHYSIOLOGY•SIGNS & SYMPTOMS•TREATMENT

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DEFINITION

It is defined as excess of adipose tissue that imparts

Health risk ,obesity means too much of body fat. It is not .The

same as being overweight. A body weight of 20percent excess over ideal weight for age, sex &height obesity is an illness where health & hence lifestyle is adversely affected by excess body fat. Most widely used method to evaluate obesity is

BMI. Which is equal to weight in kg by height in square

meter, for a healthy individual BMI value ranges from 18-25. BMI

greater than 40 individuals are said to be overweight or morbidly obese.

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Category “BMI” Range• Acceptable range(low risk) 20.0-25.0 kg/m2• Mildly overweight(increased risk)25.1-27.0 kg/m2• Moderately overweight 27.1-30.0 kg/m2• Markedly overweight/obese 30.1-40.0 kg/m2• Morbidly obese >40.0 kg/m2 Body Fat Distribution The distribution of body fat is probably the most

important factor in health and disease. The three types of fat

distribution include:• Upper Body • Normal• Lower Body An excess deposition of adipose tissue focused

on the trunk is Upper Body Obesity or ANDROID Obesity. Upper body

obesity, more specifically, visceral body fat distribution is related to

disease etiologies. An excess of deposition on the limbs or buttocks

is Lower Body Obesity or GYNOID Obesity

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OBESITY IS A COMMON PROBLEM AMONG ALL AGE GROUPS OF PEOPLE

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ETIOLOGY OBESITY results when calorie intake exceeds utilization. Taking in more calories than body can burn can lead to obesity because the body stores the unused calories as fat.

OBESITY CAN BE CAUSED DUE TO:•Eating more food than the body requirement•Drinking too much alcohol•Not getting enough exercise

TWO TYPES OF OBESITY ARE DESCRIBED:•TRUNKAL OBESITY : Where the body fat accumulates chiefly on the trunk (abdomen etc….)•Other type is where fat deposition occurs chiefly on the buttocks & limbs

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BASED ON ETIOLOGY, IT CAN BE CLASSIFIED :•SECONDARY where obesity is due to a known disorder( ex: CUSHING’S syndrome, hypothalamic disorder)•PRIMARY (no specific cause),the probable causes are….PROBABLE CAUSES OF PRIMARY OBESITY:

•Over eating•Genetic hereditary•Hypothalamic set point: •Hypothalamus has a set point regarding body weight .•If body fat is lowered the person develops ravenous appetite. They eat more until set point is achieved.• If body fat amount exceeds the set point the appetite decreases till the body fat amount is restored.• It may be noted that this set point may alter in one’s lifetime. Thus, in a middle aged person, the set point may be elevated and the person gains weight. Hypothalamic set point may be determined by genetic factors..

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•LEPTIN AND NUEROPEPTIDE Y:

LEPTIN is a poly peptide hormone discovered recently & currently under intense research. Obesity, Ischemic heart diseases & even cancer may be related to LEPTIN.•NEUROPEPTIDE Y is a neurotransmitter found in neurons of certain areas of brain. Injection of NEUROPEPTIDE Y in to hypothalamus increases appetite and food intake. LEPTIN is produced by adipose tissue, when adiposity of body rises, more LEPTIN is produced LEPTIN is carried via blood reaches hypothalamus ultimate result is decreased food intake. Probably LEPTIN causes suppression of NEUROPEPTIDE Y synthesis. IT APPEARS HUMAN OBESITY IS DUE TO LACK OF LEPTIN RECEPTORS.

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OTHER FACTORS THAT AFFECT WEIGHT INCLUDE: The way we eat when we are children can affect the

way we eat as adults, The way we eat over many years becomes a habit. It affects what we eat, when we eat & how much we eat.

Many people do not have time to plan & take healthy meals.

More people work desk jobs compared to more active jobs in the past.

Sometimes medical problems and treatment cause weight gain including:

Underactive thyroid gland (HYPOTHYROIDISM)

Medicines such as BIRTH CONTROL PILLS, ANTIDEPRESSANTS, ANTIPSYCHOTRICS ,CORTICOSTEROIDS.

Other factors are STRESS, ANXIETY, DEPRESSION, NOT SLEEPING WELL.

For women: MENOPAUSE: Women may gain 12 to 15 pounds

during menopause, and not losing weight they gained during pregnancy.

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PATHOPHYSIOLOGY The lipid storing cells, ADIPOCYTES comprise the adipose tissue & are present in VASCULAR & STROMAL compartment in the body. Besides their role in fat storage, cells also release ENDOCRINE REGULATING MOLECULES.

These molecules include •Energy regulatory hormone(LEPTIN)

•CYTOKINES (TNF-alpha, IL-6)• Insulin sensitivity regulating agents(ADIPONECTIN,RESISTIN & RBP-4)• PROTHROMBIC factors(PLASMINOGEN ACTIVATOR INHIBITOR)• B.P. regulating agent(ANGIOTENSINOGEN) Adipose mass may be increased due to enlargement

of adipose cells due to excess of intracellular lipid deposition as well as due to increased number of ADIPOCYTES.

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Recently, two obesity genes have been found:

•‘ob’ gene and its protein product leptin•‘db’ gene and its protein product leptin receptor. The fine balance of body weight is maintained by an internal set point or lipostat that can sense the quality of the energy stores and appropriately regulate the food intake as well as the energy expenditure. The neurohumoral mechanisms regulate the energy equation and therefore influence body weight. There are three components of this system:•AFFERENT SYSTEM:

•Generates humoral signals from the adipose (leptin), pancreas (insulin) and stomach (ghrelin)•CENTRAL PROCESSING UNIT: •Located primarily in hypothalamus which integrates the afferent signals.•EFFECTOR SYSTEM: Carries out “orders” from the hypothalamic nuclei in the form of feeding behaviour and energy expenditure.

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•Insulin and leptin activate catabolic circuits

• Ghrelin Produced in the stomach, ghrelin levels rise sharply before every meal and fall promptly when the stomach is “filled”.•leptin has a more important role than insulin in the central nervous system control of energy homeostasis. •Adipocytes communicate with the hypothalamus centers that control appetite and energy expenditure by secreting leptin, a member of the cytokine family.

•When energy is stored in the form of adipose tissue, the resultant high levels of leptin cross the blood-brain barrier, binding to leptin receptors. Leptin receptor signalling has two effects:

•It inhibits anabolic circuits that normally promote food intake and inhibits energy expenditure.•It triggers catabolic circuits through a set of neurons..

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•The net effect of leptin is to reduce food intake and promote energy expenditure.

•This cycle is reversed when adipose tissue is lost and leptin levels are reduced below a threshold.

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•ADIPOCYTES communicate with the hypothalamic centre that control appetite & energy expenditure by secreting polypeptide hormone called LEPTIN.•LEPTIN acts as ANTI OBESITY FACTOR.•LEPTIN mediates its affect by binding to & activating LEPTIN receptors in the HYPOTHALAMUS.

•In experimental animals , Triggering of LEPTIN receptors inhibits appetite & increases energy expenditure, physical activity & production of heat.•THERMOGENESIS is controlled at least in part by LEPTIN RECEPTOR MEDIATED HYPOTHALAMIC SIGNALS that increase the release of NOREPINEPHRINE from the SYMPATHETIC NERVE ENDINGS in the ADIPOSE TISSUE.

•The fat cells express beta-3 adrenergic receptors that when

stimulated by NOREPINEPHRINE cause fatty acid hydrolysis & also uncouple energy production by storage.•Thus fats are literally burned & the energy so produced -dissipated as heat

MECHANISM

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SIGNS & SYMPTOMS• Large body frame.• Difficulty in doing daily activities. • Lethargy • Breathlessness• Disproportionate facial features• Breast region adiposity - (sagging fat cells) in boys• Big belly (abdomen)• Male external genitalia may appear disproportionately small• Early arrival of puberty• Flabby fat in the upper arms and thighs• Knock-knees (Genu valgum) is common• Menstrual problem• Increased sweating• Snoring• Difficulty in sleeping

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SEQUELAE OF OBESITY: Marked obesity is a serious health disorder & may predispose to a number of clinical disorders & pathological changes as described below.......

MORPHOLOGICAL FEATURES: Obesity is associated with increased adipose stores in subcutaneous tissue, skeletal muscles, internal organs such as kidney, heart, liver. FATTY LIVER is also most common in obese individuals. There is increase in both size & number of adipocytes i.e. there is both hypertrophy & hyperplasia.

METABOLIC CHANGES:• HYPERINSULINAEMIA• TYPE II DIABETES MELITUS• HYPERTENSION

• HYPERLIPOPROTEINAEMIA •ATHEROSCLEROSIS

• NON ALCOHOLIC FATTY LIVER DISEASE • CHOLELITHIASIS• HYPOVENTILATION SYNDROME• OSTEOARTHRITIS•CANCER

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MANAGING OBESITY-TREATMENTLIFESTYLE MODIFICATION1. Dietary changes2. Low fat high carbohydrate diets3. Fixed energy deficit diets4. Meal replacements5. Very low calorie diets6. High protein low carbohydrate dietsPHYSICAL ACTIVITY

BEHAVIORAL MANAGEMENT

ANTI OBESITY DRUGSThere are currently two categories of antiobesity drugs: Those that act on the gastrointestinal system (pancreatic lipase inhibitors) and those that act on the central nervous system to primarily suppress appetite.

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Drugs acting on the gastrointestinal system: pancreatic lipase inhibitors

Orlistat inhibits pancreatic and gastric lipase thereby decreasing ingested triglyceride hydrolysis.

It produces a dose dependent reduction in dietary fat absorption: weight loss in obese subjects largely results from reduction in fat intake to avoid gastrointestinal effects.

Vitamin supplementation (especially of vitamin D) may be considered if there is concern about deficiency of fat soluble vitamins.

Centrally acting antiobesity drugs Sibutramine promotes a sense of satiety through its central

action as a serotonin and norepinephrine reuptake inhibitor. In addition, it may mitigate against the fall in thermogenesis

through stimulation of peripheral norepinephrine receptors. It is used in the adjunctive management of obesity in

individuals with a BMI of 30 kg/m2 or more (and no associated comorbidity) or in individuals with a BMI of 27 kg/m2 or more in the presence of other risk factors such as type 2 diabetes or hypercholesterolaemia.

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SIBUTRAMINE •Sibutramine, originally intended as an antidepressant, •The drug inhibits the reuptake of serotonin and noradrenaline at the hypothalamic sites that regulate food intake. •Its main effects are to reduce food intake and cause dose-dependent weight loss. •Produces a reduction in waist circumference (i.e. a reduction in visceral fat), a decrease in plasma triglycerides and VLDL, but an increase in HDL•There is some evidence that the weight loss is associated with higher energy expenditure, possibly through an increase in thermogenesis mediated by the sympathetic nervous system. Unwanted effects • Increases heart rate and blood pressure. •The drug is contraindicated if cardiovascular disease is present or if the systolic or diastolic pressure is raised by 10 mmHg or more. •Other unwanted effects include dry mouth, constipation and insomnia.

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•Orlistat reacts with serine residues at the active sites of gastric and pancreatic lipases, irreversibly inhibiting the enzymes and thereby preventing the breakdown of dietary fat to fatty acids and glycerols. It therefore causes a dose-related decrease in fat absorption and a corresponding increase in faecal fat excretion

ORLISTAT

•Orlistat is also reported to be effective in patients suffering from type 2 diabetes and other complications of obesity, to reduce leptin levels and blood pressure, to protect against weight loss-induced changes in biliary secretion, to delay gastric emptying and gastric secretion, to improve several important metabolic parameters, and not to interfere with the release or action of thyroid and other important hormones o It does not induce changes in energy expenditure

Unwanted effects

•Abdominal cramps, •flatus with discharge

•faecal incontinence

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•Phentermine (30 mg in the morning or 8 mg before mealsAdverse effects e.g., increased blood pressure, palpitations, arrhythmias, •Diethylpropion(25 mg before meals or 75 mg of extended-release formulation every morning)Diethylpropion is one of the safest noradrenergic appetite suppressants and can be used in patients with mild to moderate hypertension or angina, but it should not be used in patients with severe hypertension or significant cardiovascular disease.•Rimonabant  is a recently developed anti-obesity drug. It also acts centrally on the brain and decreases appetite. It may also act peripherally by increasing thermogenesis and therefore increasing energy expenditure.  Increases serotonin release that then activates serotonin receptors in the brain to regulate food intake and body weight, but unfortunately, this drug also causes lesions in heart valves,

•Fen-phen

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OVERVIEWAll of these drugs induce several adverse effects. Although most of these adverse effects are mild and transient, the prolonged use of adrenergic or serotonergic anorectic drugs, or their use as combination treatment, may induce serious and potentially life-threatening complications, such as primary pulmonary hypertension or valvular heart disease. The adrenergic appetite-suppressing drugs are not recommended for the treatment of obesity, since their safety has never been evaluated in long term clinical trials, and because of their stimulatory effects on the cardiovascular and nervous systems.

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SURGICAL TREATMENT IMPORTANT CONSIDERATIONS FOR All WEIGHT LOSS SURGERY-

Surgery should not be considered until all other options have been evaluated1. Weight loss surgery is not a cosmetic surgery.2. The decision to elect surgical treatment requires an

assessment of the risk and benefit to you and the meticulous performance of the appropriate surgical procedure.

3. The success of weight loss surgery is dependent on your long term lifestyle changes in diet, exercise and behavior modification.

4. In a survey of over 10,000 patients, the mortality rate for weight loss surgery was 0.30%

What defines successful weight loss surgery?

The ability to achieve and maintain loss of at least 50% of excess body weight without having substantial adverse effects.

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Laparoscopic approach to weight loss surgery All the procedures are performed Laparoscopically. When a Laparoscopic operation is performed, a small video camera inserted into the abdomen allows the surgeon to conduct and view the surgery on a video monitor. The camera and surgical instruments are usually inserted through small incisions made in the abdominal wall.

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Laparoscopic Sleeve Gastrectomy

• Approximately 2/3 of the stomach is stapled off. This results in a stomach, which is roughly the size and shape of a banana or Sleeve. • It reduces hunger because hunger

stimulating hormone producing part of stomach is removed.

• 90-98% resolution of Diabetes, Hypertension, hyperlipidemia, Sleep apnea,knee joint pain and much quality of life.• Provides satiety with small amount of food.• No malabsorption

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Laparoscopic Gastric Banding

1. The gastric banding is the least invasive of all procedures.

2. An adjustable silicon band is placed around the stomach to create a small stomach. Small quantity of food can fill up the small stomach providing satisfaction/satiety to the person.

• Narrow outlet of this small stomach delays progression of food into intestine – person feels full for longer period. • The size of the stomach opening can be adjusted by injecting saline through a button under the skin. Person is able to eat smaller meals at long interval. 

• The mean weight loss at two years after surgery is 40-55% of excess weight.

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Intra Gastric Balloon  

The Intra Gastric Balloon is a soft, expandable, silicone balloon that is placed inside the stomach via endoscopy that enters through the mouth and into the stomach with or without sedation.

reduces the capacity of the stomach. This creates a feeling of fullness for the patient and does not allow for overeating, therefore allowing the patient to effectively diet without feeling continuously hungry. This procedure generally takes 20 minutes.•Digestion and absorption is normal.•When eating less the body draws the required energy from its own fat•The mean weight loss at six months after is 15-25 Kgs

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Gastric Imbrication•The Gastric Imbrication is a laparoscopic (keyhole)

procedure.•It is a reversible procedure which involves only 3 tiny cuts on the abdomen and the stomach is folded over itself and stitched. •The tiny cuts are so small that they don’t require any stitches and the patient walks home the next morning.•The procedure results in reducing the capacity of the stomach to 100-150 ml and as a result the patient gets a feeling satiety with a small meal.

•It does not require any stapling, disconnecting or reconnecting the intestines and food absorption is normal.

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Liposuction,

Also known as lipoplasty ("fat modeling"), liposculpture suction lipectomy ("suction-assisted fat removal") or simply lipo is a cosmetic surgery operation that removes fat from many different sites on the human body.

• Areas affected can range from abdomen, thighs and buttocks, to the neck, backs of the arms and elsewhere.

Possible Liposuction Risks1. Infection2. Extended healing time3. Fat or blood clots4. Excessive fluid loss can lead to

shock5. Fluid accumulation6. Friction burns7. Damage to the skin or nerves8. Damage to vital organs

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REFERENCE:•Pathological basis of disesase. ROBBINS 7th edition 2005•RANG & DALE’S pharmocology 6th edition•Text book of pathology HARSH MOHAN 6th edition•Concise medical physiology by CHAUDHURI 3rd edition•Pharmacotherapeutics by DIPIRO•www.bellenews.com•www.geniusbeauty.com•www.diabetespharmacist.com•www.healthheap.com•www.coolhealthtips.com•www.lowdensitylifestyle.com•www.medscape.com•www.life123.com•www.teenobesity.net•Obesityinformations.info•www.mrhealthtips.com•www.immortalhumans.com

THANK YOU…….