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Block 10 Week 2 > Usera > Pancreas > Flashcards

Usera > Pancreas Flashcards

1
Q

what are the 4 types of pancreatic islet cells?

A
  1. Beta
  2. Alpha
  3. Delta
  4. PP
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2
Q

what do Beta cells secrete?

A

insulin

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3
Q

what do Alpha cells secrete?

A

glucagon

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4
Q

what do delta cells secrete?

A

somatostatin

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5
Q

what do PP cells secrete?

A

pancreatic polypeptide

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6
Q

how are the 4 main cell types of the pancreas identified?

A

ultrastructural characteristics (EM) & hormone content

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7
Q

what are the 2 minor cell types?

A

D1 & enterochromaffin cells

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8
Q

what do D1 cells secrete?

A

VIP

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9
Q

what do enterochromaffin cells secrete?

A

serotonin

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10
Q

what do alpha granules look like?

A

round, dense, w/ a thin halo

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11
Q

what do beta granules look like?

A

crystalline core w/ a wide halo

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12
Q

what do delta granules look like?

A

round, less dense core w/ a thin halo

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13
Q

what do PP granules look like?

A

small, hyperdense cores

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14
Q

what are the 2 main disorders of the pancreatic islet cells?

A

diabetes mellitus
AND
pancreatic endocrine tumors

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15
Q

what is diabetes mellitus a dysfxn or loss of?

A

pancreatic BETA cells

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16
Q

what are pancreatic endocrine tumors?

A

abnormal proliferation of pancreatic islet cells

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17
Q

T/F: DM is a single disease entity

A

FALSE

it’s a group of metabolic disorders sharing hyperglycemia

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18
Q

what does DM result from defects in?

A

insulin secretion
insulin action
or both

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19
Q

what are chronic hyperglycemia & metabolic dysregulation assoc w/?

A

secondary organ damage, esp in kidneys, eyes, nerves, & BVs

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20
Q

how many ppl are affected by DM?

A

> 20 million children & adults

>140 million people worldwide

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21
Q

what is the leading cause of ESRD, adult-onset blindness, & non-traumatic lower extremity amputation?

A

DM

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22
Q

how many adults are pre-diabetic?

A

54 million

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23
Q

what is pre-diabetic?

A

elevated blood sugar not meeting criteria for dx of DM

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24
Q

what is the estimated lifetime risk of being diagnosed w/ DM if you were born in 2000 and you are male?

A

1 in 3

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25
Q

what is the estimated lifetime risk of being diagnosed w/ DM if you were born in 2000 and you are female?

A

2 in 5

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26
Q

what is the estimated lifetime risk of being diagnosed w/ DM if you were born in 2000 and you are an ethnic minority?

A

2-5x higher in AA, hispanic, & native american communities (cp to non-hispanic egg whites)

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27
Q

what is the cost of DM in the US (in 2011)?

A

174 billion bucks yo

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28
Q

what region of the US is more affected by DM?

A

the DIRTY SOUTH

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29
Q

to be diagnosed w/ DM, you have to have (how many?) of 3 criteria

A

only 1

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30
Q

what are the 3 possible criteria for DM dx?

A
  1. random blood glucose >200 w/ classic sx
  2. fasting blood glucose >126 more than once
  3. abn glucose tolerance test w/ blood glucose >200 after std carb load
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31
Q

what is a NORMAL fasting blood sugar?

A

<100

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32
Q

what is a NORMAL glucose tolerance test blood sugar?

A

<140

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33
Q

what is type 1 DM?

A

an ABSOLUTE DEFICIENCY of INSULIN d/t AUTOIMMUNE destruction of beta cell mass

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34
Q

which cells are involved in the type 1 DM immune response?

A

t-lymphs mount an attack against pancreatic beta cell ag

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35
Q

what is type 2 DM?

A

PERIPHERAL RESISTANCE to insulin action

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36
Q

what happens w/ insulin in type 2 DM?

A

inadequate secretion by pancreatic beta cells creates a RELATIVE INSULIN DEFICIENCY

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37
Q

do 90-95% of diabetics have type 1 or type 2?

A

type 2

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38
Q

T/F: to have DM type 2, you have to be overweight

A

you don’t HAVE to be

but most ARE

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39
Q

which gene contributes over 50% of the susceptibility to DM1?

A

HLA locus on 6p21

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40
Q

what haplotypes do 90-95% of whites w/ DM1 have?

A

either HLA-DR3 or HLA-DR4

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41
Q

40-50% of DM1 pts have what genetic thing?

A

DR3/DR4 heterozygotes

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42
Q

which 4 non-HLA genes are involved in DM1?

A
  1. insulin (VNTR)
  2. CTLA4
  3. PTPN22
  4. CD25
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43
Q

what viruses can cause DM1?

A 
mumps
rubella
coxsackie B
CMV
"others"
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44
Q

what are the 3 general ways that viruses can cause DM1?

A

bystander
molecular mimicry
precipitating virus

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45
Q

how does the “bystander” pathway work to cause DM1?

A

viral infection induces islet cell injury/inflammation > exposure to self beta cell ag > activation of autoreactive T cells

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46
Q

how does the “molecular mimicry” pathway cause DM1?

A

viral proteins mimic beta cell ag & the immune response cross-reacts

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47
Q

how does the “precipitating virus” pathway cause DM?

A

viral infection early in life could persist in tissue

subsequent infection w/ a similar virus could elicit an immune response against infected islet cells

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48
Q

what happens prior to any signs & sx in DM1?

A

slow progressive destruction of beta islet cells

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49
Q

how many (%) of the beta cells have been destroyed before hyperglycemia & ketosis occur in DM1?

A

> 90%

50
Q

what is the fundamental immune abnormality in DM1?

A

failure of self-tolerance

51
Q

what 3 env factors are involved w/ DM2?

A

sedentary lifestyle
diet
obesity

52
Q

what is the concordance rate of DM2 in monozygotic twins?

A

35-60%

53
Q

what doubles the lifetime risk of getting DM2?

A

if both parents are affected

54
Q

what is the strongest gene association in DM2?

A

TCF7L2

55
Q

is DM2 linked to HLA genes?

A

NOPE

that’s DM1

56
Q

what are the 2 metabolic deficits of DM2?

A
  1. insulin resistance

2. beta cell dysfxn (relative insulin deficiency)

57
Q

what is insulin resistance?

A

decreased ability of peripheral tissues to respond to insulin

58
Q

what is relative insulin deficiency in DM2?

A

inadequate insulin secretion in the face of hyperglycemia

59
Q

what is the PRIMARY event in DM2?

A

insulin RESISTANCE
it predates hyperglycemia
and THEN you get beta cell dysfxn in increasing degrees

60
Q

what 3 things does insulin do to adipose tissue normally?

A

INC glucose uptake
INC lipogenesis
DEC lipolysis

61
Q

what 3 things does insulin do to striated muscle normally?

A

INC glucose uptake
INC glycogen synth
INC protein synth

62
Q

what 3 things does insulin do to the liver normally?

A

DEC gluconeogenesis
INC glycogen synth
INC lipogenesis

63
Q

what % of pts have visceral obesity?

A

80%

64
Q

T/F: obese pts have insulin resistance w/o hyperglycemia

A

TRUE

in states of fat XS, there is a fundamental abnormality in insulin signaling

65
Q

in states of insulin resistance, what happens to insulin secretion?

A

it is initially higher for each level of glucose

66
Q

what does hyperinsulinemic state compensate for in DM2?

A

peripheral insulin resistance

so you can maintain normal blood glucose levels

67
Q

what happens when beta cell compensation becomes inadequate?

A

you get diabetes
that sucks
a lot

68
Q

what happens to the islet cells in DM2?

A

amyloid replacement

69
Q

what is glucotoxicity?

A

persistent hyperglycemia

70
Q

what is HGBA1C?

A

glycosylated hemoglobin (hb bound to glucose)

71
Q

what is the BEST assessment of glycemic control?

A

HbA1C

72
Q

how is HbA1C formed?

A

nonenzymatic covalent addition of glucose moieties to hemoglobin in RBCs

73
Q

what is the time span for HbA1C?

A

120 days

i.e. the lifespan of an RBC

74
Q

what is the HbA1C in a non-diabetic?

A

<7%

75
Q

when do advanced glycosylation end (AGE) pdts form?

A

when nonenzymatic rxns occur btwn glucose & the amino groups of intra & extracellular proteins

76
Q

what can accelerate AGE formation?

A

hyperglycemia

77
Q

what can AGE pdts cross-link to?

A

extracellular matrix proteins

78
Q

what happens when AGE pdts cross-link extracellular matrix proteins?

A

DEC vascular elasticity
INC protein deposition
ENTRAP non-glycated plasma & interstitial proteins (LDL)

79
Q

which tissues do not require insulin for glucose transport?

A 
nerves
lenses 
kidneys
BVs
(these are the tissues that are affected in diabetics)
80
Q

what happens to nerves in hyperglycemic states?

A

diabetic neuropathy

i.e. glucose neurotoxicity

81
Q

what is the etiology of peripheral tissue damage d/t persistent hyperglycemia?

A

INC intracellular glucose in tissues that do NOT require insulin for transport > DEC glutathione pdtion > INC susceptibility to oxidative stress

82
Q

what is macrovascular dz?

A

accelerated atehrosclerosis involving the aorta & large & medium arteries

83
Q

what is a HALLMARK of DM?

A

macrovascular dz

84
Q

what is the most common cause of death in DM?

A

MI d/t atherosclerosis of coronary arteries (equally common in M & F)

85
Q

how can macrovascular dz manifest in a pt?

A

(besides MI & death)

gangrene of lower extremities

86
Q

what type of arteriosclerosis is assoc w/ HTN?

A

hyaline

87
Q

what is microvascular dz?

A

diabetic microangiopathy

diffuse thickening of the BM

88
Q

where is microvascular dz most evident (MICRO is your hint)

A

capillaries

89
Q

what is weird about diabetic capillaries?

A

they are leakier than normal to plasma proteins

90
Q

what underlies the development of diabetic nephropathy, retinopathy, & some types of neuropathy?

A

microvascular dz

91
Q

what is the 2nd most common cause of death in DM?

A

diabetic nephropathy d/t microvascular dz (MI d/t macrovascular was #1)

92
Q

where do you get lesions in diabetic nephropathy?

A

glomerular lesions
&
renal vascular lesions (primarily arteriolosclerosis)

93
Q

what are glomerular lesions?

A

capillary BM thickening (bc glomerular lesions are seen in diabetic nephropathy which is d/t microvascular dz)

94
Q

what do ALL cases of diabetic nephropathy have?

A

glomerular lesions

95
Q

what can you see on EM w/ glomerular lesions?

A

diffuse mesangiosclerosis

96
Q

what does a kidney look like (gross) in a pt w/ nephrosclerosis & long-standing diabetes?

A

bumpy and gross and red

97
Q

what can you see on PAS stain w/ glomerular lesions?

A

Kimmelsteil-Wilson nodules

98
Q

what are the (6) oral manifestations of DM?

A
  1. dental caries
  2. salivary dysfxn & xerostomia
  3. oral mucosal dz
  4. oral infxn
  5. gingivitis & periodontal dz
  6. taste & other neurosensory disorders
99
Q

what contributes to dental caries in DM pts?

A

diet

decreased salivary flow

100
Q

what oral mucosal dz can DM pts get?

A

lichen planus

aphthous stomatitis

101
Q

what oral infxn are DM pts prone to?

A

oral candidiasis

102
Q

what does candidiasis look like?

A

white shit in your mouth

103
Q

what does periodontal disease look like?

A

brown tooth borders (granulomatous tissue at gingival margin)

104
Q

what pt group presents w/ DM1?

A

the young

105
Q

what are the dominant clinical features of DM1 (there are 4)

A

polyuria
polydipsia
polyphagia
ketoacidosis

106
Q

what does insulin deficiency result in?

A

catabolic state affecting glucose, protein, & fat metabolism

insulin is a major anabolic hormone

107
Q

what pt population should you suspect DM2 in?

A

older (>40 yo)

obese

108
Q

when is a dx of DM2 usu made?

A

after routine blood or urine testing in an asymptomatic pt

109
Q

do DM2 pts get ketoacidosis?

A

yeah but it’s infrequent bc higher portal vein insulin levels prevent unchecked FA oxidation & ketone body formation is restricted

110
Q

what happens when DM2 is decompensated?

A

hyperosmotic nonketotic coma w/ severe dehydration from hyperglycemic polyuria

111
Q

what do DM2 pts NOT develop?

A

N/V
respiratory sx
(these occur in keto)

112
Q

what happens to the pancreas in DM1 (think histo)?

A

insulitis
beta cell depletion
islet atrophy

113
Q

what happens to the pancreas in DM2 (think histo)?

A

amyloid deposition in islets

114
Q

what are the most common pancreatic endocrine neoplasms?

A

neoplastic proliferation of beta cells

i.e. INSULINOMAS

115
Q

what do insulinomas do?

A

produce insulin!

116
Q

can insulinomas cause clinical hypoglycemia?

A

YOU BETCHA

117
Q

how do you differentiate acute hypoglycemia d/t INSULINOMA vs exogenous insulin injection?

A

insulinoma pts have INC INSULIN & C-PEPTIDE

118
Q

what are the 3 types of rare pancreatic endocrine neoplasms?

A

alpha cell tumors
delta cell tumors
vipoma

119
Q

what is another name for an alpha cell tumor?

A

glucagonoma

120
Q

what is another name for a delta cell tumor?

A

somatostatinoma

Block 10 Week 2 (6 decks)

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