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GI > Week 4 > Flashcards

Week 4 Flashcards

1
Q

Obesity is a problem affecting

A

the whole body

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2
Q

Metabolic syndrome is a problem primarily affecting

A

the liver

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3
Q

most common complications from obesity

A

diabetes, cancer, heart disease

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4
Q

How is obesity measured

A

BMI

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5
Q

Normal glucose tolerance test shows

A

decrease in blood glucose

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6
Q

Overweight BMI value

A

25-29.9

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7
Q

diabetics glucose tolerance test shows

A

no decrease in blood glucose

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8
Q

Features of brown adipose tissue

A
  • small
  • metabolically active, burns off adipose more readily
  • less present in body, found between muscle
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9
Q

Features of White adipose tissue

A
  • larger, “empty area where TAGs accumulate”
  • more present in body
  • associated with obesity, more proliferation and larger in size
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10
Q

increases in lipolysis causes

A
  • decrease in adiponectin
  • increase in TNFalpha
  • increase IL6
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11
Q

2 phenotypes of intestinal microbiome

A
  • bacteroidetes

- firmicutes

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12
Q

which intestinal microbiome phenotype is associated with being lean?

A

bacteroidetes

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13
Q

which intestinal microbiome phenotype is associated with being obese?

A

firmicutes

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14
Q

what type of adipose tissue surrounds the organs?

A

visceral adipose tissue (Brown)

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15
Q

What type of adipose tissue is found subcutaneously?

A

White

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16
Q

Macrophage recruitment to adipocytes induces

A

cytokine release

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17
Q

What do cytokines do

A

increase inflammation, dumbass

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18
Q

Inflammation induced by cytokines causes an increase in

A

TNF alpha

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19
Q

what does TNFalpha do?

A

downregulates insulin response to glucose

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20
Q

Downregulation of the insulin response to glucose causes

A

insulin resistance

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21
Q

recruitment of inflammatory macrophages further amplifies

A
  • inflammation

- fat cell dysfunction

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22
Q

Fat cell dysfunction leads to increased

A

circulating FFA

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23
Q

increased FFA leads to

A
  • Liver: gluconeogenesis
  • adipose: decreased glucose uptake-> increased plasma glucose
  • Pancreas: impaired glucose-stimulated insulin secretion
  • muscle-decreased glycogenesis, decreased glucose oxidation, decreased glucose uptake all leading to increased plasma glucose
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24
Q

How does obesity affect the heart

A

Causes coronary heart disease and associated problems including

  • diabetes
  • dyslipidemia
  • hypertension
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25
Q

Metabolic syndrome is characterized by the presence of

A
  • obesity
  • diabetes mellitus
  • hyperlipoproteinemia
  • hyperuricemia
  • hepatic steatosis
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26
Q

Metabolic syndrome presents with at least 3 of the following

A
  • central obesity
  • dyslipidemia
  • High BP
  • High fasting plasma glucose
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27
Q

Metabolic syndrome presents with at least 3 of the following

A
  • central obesity
  • dyslipidemia
  • High BP
  • High fasting plasma glucose
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28
Q

Central obesity is defined as

A

Large waist circumference

  • male: >102cm/40 in
  • Female: >88cm/35in
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29
Q

Dyslipidemia is defined as

A
  • TAG >1.7

- HDL-C < 40(male), <50(female)

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30
Q

What is a high fasting plasma glucose?

A

> 6.1

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31
Q

What are hepatic hallmarks of metabolic syndrome?

A

liver steatosis and steatohepatitis

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32
Q

Fatty liver disease is characterized by

A
  • reduced glucose processing & utilization
  • increased gluconeogenesis
  • increased FA deposition within organs
  • implications(decreased/toxic) for drug metabolism
  • inflammation
  • altered transaminases
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33
Q

Problems associated with NASH/NAFDL

A
  • fatty liver disease

- end stage cirrhosis

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34
Q

End stage cirrhosis is characterized by

A

increased bilirubin and decreased serum albumin

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35
Q

What controls body mass?

A

adiponectin

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36
Q

increased inflammation->increased inflammatory cytokines-> impacts adipose-> insulin doesn’t work effectively -> ___ and ____

A
  • decrease adiponectin

- increase FFA

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37
Q

A decrease in adiponectin leads to what in the muscle and liver

A
  • muscle: insulin resistance, decrease in glucose utilization
  • Liver: insulin resistance, increased gluconeogenesis and hepatic steatosis
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38
Q

How do adiocytokine concentrations change during lipolysis & inflammation in obesity?

A

TNF alpha, IL-6 increase

39
Q

How do hormones concentrations change during lipolysis & inflammation in obesity?

A

leptin increases, adiponectin decreases

40
Q

What increases in steatosis?

A
  • TAG synthesis

- FFA beta ox.

41
Q

Liver Disease Progress

A

normal liver-steatosis-steatohepatitis(NASH)-fibrosis/cirrhosis-HCC

42
Q

How do hepatocyte mitochondria change during liver disease?

A

Iron, ROS, and lipid peroxidation increase

43
Q

Lifestyle treatment for metabolic syndrome

A

diet, exercise

44
Q

medication treatment for metabolic syndrome

A
  • drugs to lower blood sugar (biguanide)
  • metformin(turns off gluconeogenesis and FA metabolism)
  • BP medication
45
Q

Treatments for obesity?

A

diet, exercise, bariatric surgery when those dont work

46
Q

Types of Bariatric surgery?

A
  • Roux-en-Y
  • lap band
  • vertical sleeve gastrectomy
47
Q

What is Roux-en-Y

A
  • bypasses the K cells of the SI, decreases circulating GIP

- Bypasses L cells of the SI, but increases GLP

48
Q

GLP is responsible for

A

feeling of fullness

49
Q

Pro’s for roux-en-y

A
  • long term weight loss
  • little malabsorption
  • few vitamin/mineral deficiencies
50
Q

Cons to roux-en-y

A

difficult procedure

51
Q

Pros to lap band

A
  • few dietary deficiencies
  • adjustable
  • easy surgical procedure
52
Q

Cons to lap band

A

-less weight loss

53
Q

Pros to vertical sleeve gastrectomy

A
  • good weight loss
  • few dietary deficiencies
  • hunger producing hormones lowered
54
Q

What happens when small amounts of alcohol are ingested?

A

body can still process the alcohol without much damage

55
Q

What happens with large amounts of alcohol are ingested?

A

body can’t process the alcohol fast enough and enzymes become saturated

56
Q

Ethanol is processed by ____, producing ___ and ___

A

-alcohol dehydrogenase (ADH)

  • NADH
  • acetaldehyde
57
Q

Acetaldehyde is processed by ____ producing ___ and ___

A

-aldehyde dehydrogenase

  • NADH
  • acetate
58
Q

Acetaldehyde is processed by ____ producing ___ and ___

A

-aldehyde dehydrogenase

  • NADH
  • acetate(Acetic Acid)
59
Q

why is large amounts of alcohol consumption bad?

A

Acetaldehyde builds up, becomes toxic and damages DNA

60
Q

Acetaldehyde leads to

A

adducts formation, and acetaldehyde can no longer be removed from the system

61
Q

Main complications of alcoholic liver disease

A
  • Steatohepatitis
  • fibrosis
  • cirrhosis
  • hepatocellular carcinoma (HCC)
62
Q

How do the hepatocytes metabolize alcohol

A

via cytosolic ADH and reticular cyP450, leading to an increase in acetaldehyde, ROS(reactive O2 species) and NADH

63
Q

What primarily metabolizes low amounts of alcohol?

A

cytosolic ADH

64
Q

What primarily metabolizes large amounts of alcohol?

A
  • cytosolic ADH

- reticular cyP450

65
Q

What is primarily responsible for the formation of ROS?

A

cyP450

66
Q

A low NAD/NADH ratio leads to

A

cessation of glycolysis and reduced ATP

67
Q

A low NAD/NAHD ratio is caused by

A

increased NADH due to cyP450 metabolizing high amounts of alcohol

68
Q

Reduced ATP affects

A

ion transport and concentration

69
Q

A reduced ATP in the liver would result in

A
  • higher than normal Na+ and Ca2+ in the hepatocyte
  • decreased hepatocyte regeneration (b/c it requires ATP)
  • increased lipgenesis/decreased beta-ox (due to NADH increase), which leads to steatosis(fatty liver)
70
Q

A higher than normal Na+ and Ca2+ in the hepatocyte causes

A

decreased Na/K pump activity, resulting in increased intracellular Na+, leading to decreased Na+/Ca2+ exchange, resulting in increased intracellular Ca2+

71
Q

Kupffer cells and Alcoholic Liver Disease

A
  • metabolize alcohol via cyP450, leading to an increase in acetaldehyde and ROS
  • increased Mg2+ loss from cells with increased Na+ and Ca2+ content
  • production of inflammatory cytokines (including IL-1beta and alpha SMA)
72
Q

Hepatic Stellate cells and Alcoholic Liver Disease

A
  • activation of inflammatory cytokines released from Kupffer cells
  • Vitamin A loss
  • Increased collagen production
  • Endotoxin production
73
Q

How does Alcoholic liver disease affect the brain?

A
  • vessel vasospasm due to intracellular Na+ and Ca2+ increase
  • malnutrition
  • stroke, ischemia, brain hemorrhage
74
Q

How does alcoholic liver disease affect the skeletal muscle

A
  • muscle fiber loss (to support energy production and increased cell death)
  • reduced glucose uptake
  • sarcopenia, glucose metabolism impairment
75
Q

How does alcoholic liver disease affect the pancreas?

A
  • higher than normal intracellular Ca2+
  • vasospasms
  • ectopic activation of pancreatic enzymes
  • malnutrition, pancreatitis
76
Q

How does alcoholic liver disease affect the heart?

A
  • higher intracellular Ca2+
  • altered Ca2+ cycling causing altered contration and relaxation cycle
  • reduced ATP production
  • alcoholic cardiomyopathy
77
Q

Which extraneous organ has cyP450?

A

the heart

78
Q

How does G6P enter the ER?

A

A transporter

79
Q

What happens to G6P once its inside the ER?

A

G6Phosphatase removes phosphate, producing glucose + Pi

80
Q

What does Pi do inside of the ER?

A

brings in Ca2+ ions through the SERCA pump

81
Q

What happens to Ca2+ inside of the ER?

A

Sequestered to lower Ca2+

82
Q

What happens to Ca2+ inside of the ER?

A

Sequestered to lower Ca2+ concentration in the cell (Ca2+ concentration rises in ER)

83
Q

What is entrapment of Ca2_

A

lowering Ca2+ concentration in the cell by trapping Ca2+ in the ER

84
Q

What is IP3 signalling?

A

Release of Ca2+(through IP3R) and Pi(through T3 ) from the ER in response to IP3 (

85
Q

There is a dose dependent relationship between

A

Ca2+ uptake and G6Phosphatase

86
Q

The more alcohol that is ingested, the less

A

Ca2+ you are able to retain

87
Q

Alcohol causes a defect in

A

G6Phosphatase, so you cant form Ca2+/Pi complexes, leading to decreased ER uptake and Ca2+ entrapment

88
Q

Excess Ca2+ in the cytosol causes

A

Activation of 2nd messenger systems

89
Q

Pi is used to

A

sequester Ca2+ in the ER

90
Q

IP3 signals

A

Ca2+ release from the ER

91
Q

Alcohol causes a ___ in ER Ca2+ uptake

A

decrease

92
Q

Ca2+ release from the ER is proportional to

A

Ca2+ taken into the ER, which is effected by alcohol since Pi isnt created to stimulate SERCA and the sequester Ca2+ in the ER

93
Q

Net effect of alcohol/liver cancer on GLPhosphatase?

A

More Ca2+ is released from the ER than is being taken back up which leads to altered Calcium homeostasis

GI (4 decks)

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