10 - Obesity Flashcards
What is the estimated number of people living with obesity worldwide by 2030?
One billion
This is double the amount since 2010.
What are some health complications associated with obesity?
- Insulin resistance
- Type 2 diabetes
- Cardiovascular disease
- Liver disease
- Cancer
- Neurodegeneration
Obesity is a preventable disease linked to these complications.
How many deaths were attributed to obesity in 2017 according to the Global Burden of Disease study?
4.7 million
What was the percentage of adult obesity in the U.S. in 2020?
42.4%
What is the main cause of obesity?
Energy imbalance
What factors determine obesity?
- Social factors
- Environmental factors
- Psychological factors
- Genetic factors
- Biological factors
What does energy balance depend on?
Energy intake and expenditure
What happens during a positive energy balance?
Weight gain
How many kilocalories are equivalent to one pound of fat?
~3500 kcal
What is a safe and effective recommendation for weight loss?
1 lb per week
How is Body Mass Index (BMI) calculated?
Weight in kilograms divided by the square of height in meters
What BMI value categorizes a person as obese?
> 30
What is a limitation of using BMI to classify obesity?
It cannot distinguish between fat and lean masses
What waist circumference is considered a risk factor for women?
35 in or higher
What waist circumference is considered a risk factor for men?
40 in or higher
What does a waist to hip ratio above 0.90 for males indicate?
Central adiposity
What is metabolic syndrome?
A term used to define risk factors leading to increased risk of type 2 diabetes and cardiovascular disease
What are the five conditions that define metabolic syndrome?
- Central obesity
- High triacylglycerol levels
- Low HDL
- Hypertension
- High fasting glucose levels
What is the first line of treatment for metabolic syndrome?
Therapeutic lifestyle changes
What role does adipose tissue play in the body?
Acts as an energy storage depot and an endocrine organ
What are the two major types of adipose tissue?
- White adipose tissue (WAT)
- Brown adipose tissue (BAT)
What hormone is known as the ‘hunger hormone’?
Ghrelin
What is the role of lipoprotein lipase (LPL)?
Hydrolyzes triacylglycerol to free fatty acid for uptake by exercising muscle and storage in adipose tissue
What is nonalcoholic steatohepatitis (NASH)?
Accumulation of fat within the hepatocyte along with an inflammatory process
What condition is a major risk factor for obstructive sleep apnea?
Obesity
What is one of the metabolic consequences of increased central adiposity?
Reduced secretion of adiponectin
What does a waist to hip ratio above 0.85 for females indicate?
Central adiposity
What are the potential health benefits of losing more than 10% of body weight?
- Improved blood pressure
- Improved blood cholesterol
- Improved blood glucose
What are some consequences of metabolic syndrome?
- Fatty liver disease
- Chronic kidney disease
- Polycystic ovary syndrome
- Obstructive sleep apnea
- Hyperuricemia
- Cognitive decline
- Cancer
What is the significance of diagnosing metabolic syndrome?
To identify individuals at high risk of cardiovascular disease and type 2 diabetes
What is the primary diagnosis for the patient described in Case 10.1?
Obesity
What laboratory findings were significant for the patient in Case 10.1?
- Dyslipidemia
- Elevated transaminases
What is the relationship between obesity and health conditions?
Obesity is linked with hypertension, dyslipidemia, diabetes, metabolic syndrome, and NASH.
What are valuable markers of cardiovascular risk?
Body mass index and waist circumference.
What function does adipose tissue serve in the body?
Adipose tissue is an endocrine organ secreting adipokines such as leptin and adiponectin.
What is metabolic syndrome?
A cluster of conditions that leads to a fivefold increased risk for type 2 diabetes and a twofold increased risk for cardiovascular disease.
What contributes to the pathophysiology of metabolic syndrome?
Increased circulating free fatty acid leading to lipotoxicity, insulin resistance, and dysregulation of adipokines.
What is the definition of a sphygmomanometer?
A device for measuring blood pressure or tension, commonly known as a blood pressure cuff.
What is the significance of an HbA1C level in diagnosing diabetes?
An HbA1C level ≥6.5% indicates the presence of diabetes.
What are the main differences between type I and type II diabetes?
Type I is characterized by little or no insulin production due to autoimmune destruction of beta cells; Type II is characterized by insulin resistance.
What is the primary cause of insulin resistance in type II diabetes?
Obesity, particularly central or visceral obesity.
What are common complications associated with poorly managed diabetes?
Adult blindness, amputation, renal failure, heart attack, and stroke.
What happens to blood glucose levels in the progression toward type II diabetes?
Postprandial glucose levels increase due to insulin resistance, followed by an increase in fasting glucose levels.
What is the typical clinical outcome of untreated type II diabetes?
Declining insulin secretion and worsening hyperglycemia.
How does insulin regulate vascular function?
Insulin regulates both vasodilation and vasoconstriction; however, in insulin resistance, only vasoconstriction remains.
What is the role of hyperglycemia in diabetes complications?
Hyperglycemia promotes oxidative stress and tissue damage.
What is the effect of insulin resistance on lipid metabolism?
It leads to increased VLDL production and hypertriglyceridemia.
Fill in the blank: The pathologic hallmark of diabetes includes injury to the _______.
vasculature
True or False: Type I diabetes is more common in adults.
False
What lifestyle changes are encouraged for a patient with obesity and type II diabetes?
Major lifestyle changes including dietary modifications and an exercise regimen.
What are the classic complications of poorly managed diabetes?
Loss of vision, kidney failure, neurologic damage, heart attack, and stroke.
What device is suggested for monitoring blood pressure at home?
Sphygmomanometer.
What is the recommended action for a patient with elevated LDL levels?
Consideration of statin therapy.
What is the role of adipokines in obesity?
They are involved in regulating metabolic processes and inflammation.
What is the significance of an elevated BMI?
It indicates increased risk for metabolic syndrome and cardiovascular disease.
What can chronic hyperglycemia lead to in terms of vascular health?
Injury to both microvascular and macrovascular systems.
What is the effect of hyperglycemia on oxidative stress and tissue damage?
Hyperglycemia promotes oxidative stress and tissue damage, particularly in insulin-independent tissues, leading to retinopathies, nephropathies, and neuropathies
This occurs due to increased intracellular glucose levels.
What minor metabolic pathways of glucose are promoted by increased glucose levels?
The polyol and hexosamine pathways
These pathways are utilized for glucose metabolism when glucose levels are high.
What is the role of aldose reductase in glucose metabolism?
Aldose reductase converts glucose to sorbitol using NADPH as a cofactor
This reaction leads to depletion of NADPH, making cells more susceptible to oxidative damage.
What is the consequence of increased sorbitol levels in cells?
Sorbitol is osmotically active and draws water into cells, causing oxidative stress
Most cells cannot further metabolize sorbitol, contributing to cellular damage.
How does increased glycolytic flux affect fructose 6-phosphate levels?
Increased glycolytic flux raises fructose 6-phosphate levels, which can be diverted to the hexosamine pathway
This leads to the production of UDP-N-acetylglucosamine for O-glycosylation of proteins.
What is the relationship between DAG and PKC signaling?
Ectopic lipid accumulation increases diacylglycerol (DAG), activating the PKC pathway
Enhanced PKC signaling exacerbates cellular oxidative stress.
What are advanced glycation end products (AGEs) and their significance?
AGEs are formed through the auto-oxidation of glucose and interact with cellular receptors to stimulate oxidative stress
This interaction activates pathways including PKC.
What is the role of exercise in blood glucose regulation?
Exercise stimulates translocation of Glut4 and increases muscle glucose uptake via the AMPK pathway
This mechanism remains effective even in insulin-resistant patients.
What are the primary metabolic effects of insulin?
Insulin coordinates fuel utilization by tissues, favoring anabolic processes like glycogen, triacylglycerol, protein, and nucleotide synthesis
It acts mainly through binding to insulin receptors on cell membranes.
What causes excessive fat accumulation in the liver?
Increased fatty acid delivery, increased synthesis, reduced oxidation, and reduced export as VLDL
These factors contribute to hepatic steatosis.
How does obesity relate to insulin resistance?
Obesity is central to insulin resistance, diabetes, metabolic syndrome, and dyslipidemia
It disrupts normal metabolic processes.
What is crescendo angina?
Crescendo angina refers to acute episodes of chest pain occurring with increasing frequency, indicating an impending infarction
It is a critical warning sign for cardiovascular events.
What is the function of apolipoproteins?
Apolipoproteins help in the structure, receptor activity, and enzymatic regulation of lipoproteins
They are essential for lipid transport and metabolism.
What is the significance of reactive oxygen species (ROS)?
ROS can damage cellular components like DNA, RNA, proteins, and lipids
They play a crucial role in oxidative stress and cellular injury.
What are the major categories of lipoproteins?
Chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL)
These categories are based on their density and lipid content.
What role does lecithin cholesterol acyltransferase (LCAT) play?
LCAT catalyzes the conversion of cholesterol to cholesteryl esters in HDL
This process increases HDL’s capacity to transport cholesterol.
How are lipids transported in the plasma?
Lipids are transported in the plasma as components of lipoproteins
This allows hydrophobic compounds to move through the hydrophilic environment of blood.
What is the effect of statin therapy on cholesterol?
Statins lower cholesterol levels by inhibiting HMG CoA reductase
This can help manage hyperlipidemia and reduce cardiovascular risk.
What is a troponin test used for?
A troponin test is a diagnostic marker to assess heart damage and evaluate myocardial infarction risk
Elevated troponin levels indicate heart muscle injury.
What is the primary function of the reverse transport pathway in lipid metabolism?
The reverse transport pathway involves HDL, which transports cholesterol away from tissues to the liver for excretion
This pathway is crucial for maintaining cholesterol balance in the body.
What are apolipoproteins?
Apolipoproteins are protein components of lipoproteins that play a role in lipid transport.
What is the main function of chylomicrons (CM)?
Transport of dietary TAG from the intestine.
What apolipoproteins are associated with chylomicrons?
- B48
- CII
- E
What is the function of very low-density lipoproteins (VLDLs)?
Transport of endogenously synthesized TAG from the liver.
What apolipoproteins are found in VLDLs?
- B100
- CII
- E
How are low-density lipoproteins (LDLs) formed?
By the partial breakdown of intermediate-density lipoproteins (IDL) in circulation.
What is the primary role of LDLs?
Delivers cholesterol to peripheral tissues.
What apolipoprotein is associated with LDLs?
B100
What is the main function of high-density lipoproteins (HDLs)?
Removes ‘used’ cholesterol from tissues and transports it to the liver.
What apolipoproteins are found in HDLs?
- A1
- A1
- CII
- E
What is the exogenous pathway of lipid transport?
Involves the incorporation of dietary lipids into chylomicrons in the intestine.
What is required for the assembly of chylomicrons?
Microsomal triglyceride transfer protein (MTP).
What condition results from the absence of MTP?
Abetalipoproteinemia.
How do chylomicrons enter circulation?
Via the lymphatic system and then to the systemic circulation.
What proteins do chylomicrons acquire in circulation?
- Apolipoprotein C-II
- Apolipoprotein E
What is the function of lipoprotein lipase (LPL)?
Hydrolyzes triacylglycerol to free fatty acids for uptake by tissues.
What are chylomicron remnants?
Chylomicrons that have lost TAGs and are small enough to enter the liver.
What happens to chylomicron remnants in the liver?
They are taken up via receptor-mediated endocytosis by the LDL receptor and degraded.
What is familial dysbetalipoproteinemia?
A condition caused by mutations in Apo E leading to decreased chylomicron clearance.
What is the endogenous pathway of lipid transport?
Involves a mixture of dietary and de novo synthesized TAGs, predominantly synthesized in the liver.
What is the role of MTP in VLDL assembly?
Facilitates the fusion of apolipoprotein B-100 with lipid droplets.
What happens to VLDL particles in circulation?
They are converted to intermediate-density lipoproteins (IDL) or cleared by the liver.
What is the role of hepatic lipase (HL) in LDL formation?
Removes triacylglycerol and phospholipids from VLDL to form LDL.
What is the primary receptor for LDL uptake?
LDL receptor.
What enzyme binds to LDL receptors and prevents their recycling?
Proprotein convertase subtilisin/kexin type 9 (PCSK9).
What is oxidized LDL (ox-LDL)?
LDL that has undergone oxidative damage, increasing its proinflammatory properties.
How does oxidized LDL contribute to atherosclerosis?
It is recognized by scavenger receptors on macrophages, leading to foam cell formation.
Why is HDL referred to as ‘good cholesterol’?
It facilitates reverse cholesterol transport from peripheral tissues to the liver.
What is the role of ApoA-1 in HDL formation?
It binds to ABCA1 to facilitate the efflux of cholesterol and phosphatidylcholine.
What happens to free cholesterol in nascent HDL?
It is esterified by lecithin-cholesterol acyltransferase (LCAT).
What are the two fates of HDL after acquiring cholesteryl esters?
- Binds to SR-B1 releasing cholesteryl ester to the liver
- Exchanges cholesteryl esters with VLDL via CETP
What is the role of HDL in reverse cholesterol transport?
HDL facilitates the transport of cholesterol from peripheral tissues to the liver
What does CETP stand for and what is its function?
Cholesteryl ester transfer protein; it moves cholesteryl esters from HDL to VLDL in exchange for triacylglycerol
What is the result of ApoA-II binding to hepatic lipase?
It activates hepatic lipase to hydrolyze triacylglycerol to free fatty acids
Is lipoprotein (a) a risk factor for ASVD events?
Yes, lipoprotein (a) is a modest independent risk factor for atherosclerotic vascular disease events
What are dyslipidemias?
Conditions with elevated plasma cholesterol and triacylglycerols or low HDL levels
What are the two types of dyslipidemias?
- Primary dyslipidemias (genetic defects)
- Secondary dyslipidemias (lifestyle, diet, other diseases)
How is LDL cholesterol calculated?
LDL cholesterol = total cholesterol − HDL cholesterol − (total triglycerides/5)
Define hypertriglyceridemia.
A subtype of dyslipidemia with total plasma triacylglycerol levels exceeding 150 mg/dL in the fasting state
What is a major risk associated with very severe hypertriglyceridemia?
Pancreatitis
What is hypercholesterolemia?
Very high levels of cholesterol in the serum, increasing risk for coronary artery disease
What are the cardinal manifestations of chronically elevated cholesterol?
- Xanthomas
- Xanthelasma
What is choledocholithiasis?
Stone logged in the common bile duct, obstructing bile flow into the duodenum
What is a cholecystectomy?
Surgical removal of the gallbladder
What does gangrenous cholecystitis result from?
Circulatory compromise of the cystic artery leading to acute ischemia
What are the symptoms of biliary colic?
Acute postprandial right upper quadrant pain lasting <2-3 hours, possibly with vomiting
What differentiates acute cholecystitis from biliary colic?
Acute cholecystitis involves persistent pain and marked leukocytosis due to inflammation
What laboratory findings support a diagnosis of acute cholecystitis?
- Marked leukocytosis
- Elevated transaminases
- Normal bilirubin level
What is the typical clinical presentation of acute cholecystitis?
RUQ abdominal pain, fever, and vomiting
What imaging study is typically performed for suspected acute cholecystitis?
Ultrasound of the abdomen
How can recurrent episodes of abdominal pain help in diagnosis?
They can rule out certain causes like musculoskeletal or neuropathic issues
What is the significance of a normal amylase and lipase in gallbladder disease?
It argues against gallstone pancreatitis
What indicates that the stone may remain lodged in the cystic duct?
Normal transaminases and lack of extrahepatic cholestasis
Minor elevations of AST/ALT can occur in acute cholecystitis due to pericolic inflammatory change.
What are the major components of bile?
- Bile acids (bile salts)
- Phospholipids
- Cholesterol
- Bilirubin
- Electrolytes (potassium, sodium, bicarbonate)
- Small amounts of proteins and minerals
The composition of bile varies with the nutritional status of the individual.
What are the two fundamental functions of bile?
- Important in lipid digestion and absorption
- Excretion of cholesterol and bilirubin
What stimulates the release of cholecystokinin (CCK)?
Fatty acids in the duodenum
What is the role of bile acids in lipid digestion?
Facilitate emulsification of fat and formation of micelles
How is cholesterol metabolized in humans?
Synthesis and excretion of bile acids are the only significant mechanisms for eliminating excess cholesterol
What are the primary bile acids synthesized from cholesterol?
- Chenodeoxycholic acid
- Cholic acid
What is the rate-limiting step in the synthesis of primary bile acids?
Catalyzed by 7-alpha-hydroxylase (CYP7A)
What modifies primary bile acids to increase their solubility?
Conjugation via amide linkages of glycine or taurine
What are the secondary bile acids produced in the intestine?
- Deoxycholic acid
- Lithocholic acid
What does enterohepatic circulation refer to?
The movement of bile acids from the liver to the small intestine and back to the liver
What factors can lead to the formation of cholesterol gallstones?
- Certain genetic factors
- Hepatic hypersecretion of biliary cholesterol
- Gallbladder hypomotility
- Rapid phase transitions of cholesterol
- Intestinal factors
What are the three varieties of gallstones?
- Cholesterol stones
- Pigmented stones (black and brown)
- Mixed stones
What is Admirand’s Triangle used to demonstrate?
The balance between bile acids, phospholipids, and cholesterol for cholesterol solubility
What characterizes biliary colic?
Transient symptoms when a gallstone temporarily lodges in the cystic duct
What are the symptoms of cholecystitis?
Persistent RUQ pain, nausea, vomiting
What imaging findings should alert one to choledocholithiasis?
Elevation of bilirubin and alkaline phosphatase and/or a dilated common bile duct
What factors influence gallstone formation?
- Age
- Gender
- Obesity
- Metabolic syndrome
- Effects of estrogen
- Rapid weight loss
- Genetic predisposition
What were the laboratory findings in the 60-year-old female case?
WBC: 3900, Hb: 12 g/dL
Reference ranges: WBC: 4000-10,000, Hb: Not provided in detail.
What is the typical prevalence of gallstones in the U.S. population by age 40?
8%-20%
What is the proportion of gallstones found in women compared to men?
About 2-3 to 1
What are Mallory bodies?
Cytoplasmic hyaline inclusion bodies in hepatocytes indicating liver damage.
What does NAFLD stand for?
Nonalcoholic fatty liver disease.
Define steatosis.
The deleterious accumulation of excess fat in the hepatocyte.
What is the significance of steatosis in liver health?
It becomes a marker that the metabolic machinery is going awry.
What health risks does the patient have in this case?
Obesity, use of tobacco, sedentary lifestyle, unmanaged hypertension.
What supports a diagnosis of metabolic syndrome?
Dyslipidemia combined with central obesity and hypertension.
What does an inversion of the AST/ALT ratio indicate?
It can indicate alcohol abuse or nonalcoholic steatohepatitis (NASH).
What are the common causes of cirrhosis worldwide?
- Alcohol abuse
- Viral agents (hepatitis B and C)
- NASH
What does the presence of elevated bilirubin and alkaline phosphatase suggest?
More significant damage to the liver.
What does mild pancytopenia indicate in this case?
It must be accounted for in the diagnosis.
What is the gold standard for establishing a NASH diagnosis?
Liver biopsy.
What is the major complication of NASH?
Cirrhosis, which may result in decompensated liver disease or hepatocellular carcinoma.
What are the biochemical mechanisms leading to NAFLD?
- Insulin resistance
- Hormones from adipose tissue
- Nutritional factors
- Gut microbiota
- Genetic and epigenetic factors
What role does adiponectin play in NAFLD?
It decreases hepatic and systemic insulin resistance and ameliorates liver inflammation and fibrosis.
What does low adiponectin levels indicate in NAFLD?
Accelerates the progression of the disease from steatosis to NASH.
How does leptin influence NAFLD?
Higher levels of leptin are correlated with increased severity of NAFLD.
What happens to free fatty acids in NAFLD?
There is increased synthesis and decreased export in the form of VLDL.
What is the consequence of leptin resistance in NAFLD?
Increased synthesis of free fatty acids and decreased VLDL secretion.
What lifestyle changes are recommended for treating NASH?
Significant weight loss, increased exercise, and control of hypertension.
List the histologic features of NASH.
- Steatosis
- Hepatocyte ballooning degeneration with Mallory bodies
- Inflammatory infiltration of macrophages
- Fibrosis
True or False: NAFLD is the most common form of liver disease.
True.
What is a common finding in routine laboratory examinations for NAFLD?
Transaminase elevation.
What does an ultrasound reveal in this case?
An enlarged inhomogeneous liver consistent with fatty infiltration.
What is the clinical significance of splenomegaly in this case?
It suggests early portal hypertension.
What are the most common causes of cirrhosis worldwide?
Alcohol abuse, viral agents such as hepatitis B and C, and NASH
NASH stands for nonalcoholic steatohepatitis.
In alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH), what is the usual ratio of ALT to AST?
The usual ratio is inverted; AST is greater than ALT.
What are the histologic features of NASH?
Steatosis, hepatocyte ballooning degeneration with Mallory bodies, inflammatory infiltration of macrophages, and fibrosis.
What type of insulin resistance is seen in patients with NAFLD?
Selective hepatic insulin resistance.
What is impaired in patients with NAFLD regarding glucose?
Impaired glucose homeostasis.
What is enhanced in NAFLD despite impaired glucose homeostasis?
Insulin-mediated hepatic de novo lipogenesis.
What does hepatic de novo lipogenesis limit?
Fatty acid beta-oxidation.
What are the consequences of limited fatty acid beta-oxidation in NAFLD?
High free fatty acid flux, increased triacylglycerol synthesis, increased intrahepatic lipid storage, and decreased VLDL secretion.
What are adiponectin levels in NAFLD?
Adiponectin levels are low.
What resistance is observed in leptin levels in NAFLD?
Leptin resistance.
What happens to leptin levels in NAFLD?
Leptin levels increase.
What laboratory findings suggest a diagnosis of nonalcoholic steatohepatitis?
Increased AST/ALT levels
These findings indicate an inflammatory response in the liver.
What is the most likely initiating factor in the formation of plaque in the anterior descending coronary artery?
Endothelial damage
This injury leads to leukocyte infiltration and increased permeability of the vessel wall.
What is the most likely explanation for the findings in a patient with hypertension, obesity, and elevated liver enzymes?
Decreased adiponectin levels
Adiponectin levels decrease in nonalcoholic steatohepatitis, leading to fat deposition in the liver.
What is the most likely cause of acute right quadrant pain in a patient with a history of similar attacks after meals?
Obstruction of her cystic duct by a gallstone
This condition is indicative of acute cholecystitis.
What pathologic process is described in a patient with long-standing type II diabetes experiencing vision problems?
Nonenzymatic glycation of proteins
This process contributes to complications such as diabetic retinopathy.
What is the most likely diagnosis for a patient with obesity, elevated blood pressure, and elevated blood glucose levels?
Type 2 diabetes
Defined by fasting plasma glucose levels above 126 mg/dL.
Which metabolic pathway in the liver has diminished activity in a patient with type 2 diabetes?
Decreased beta-oxidation
Increased lipid peroxidation and high fatty acid levels inhibit beta-oxidation.
What is the most likely preliminary diagnosis causing increased serum liver enzyme activity in a patient with hypertension and obesity?
Nonalcoholic steatohepatitis
This condition is associated with metabolic syndrome.
What is the most likely explanation for why exercise would improve laboratory findings in a patient?
Activates AMPK pathway
AMPK activation increases glucose uptake by muscle through GLUT4 translocation.
What is the most likely cause of severe abdominal pain in a patient with metabolic syndrome?
Cholecystitis
Gallstones can obstruct the bile duct, causing symptoms consistent with this diagnosis.
