Usera > Pancreas Flashcards
(120 cards)
1
Q
what are the 4 types of pancreatic islet cells?
A
- Beta
- Alpha
- Delta
- PP
2
Q
what do Beta cells secrete?
A
insulin
3
Q
what do Alpha cells secrete?
A
glucagon
4
Q
what do delta cells secrete?
A
somatostatin
5
Q
what do PP cells secrete?
A
pancreatic polypeptide
6
Q
how are the 4 main cell types of the pancreas identified?
A
ultrastructural characteristics (EM) & hormone content
7
Q
what are the 2 minor cell types?
A
D1 & enterochromaffin cells
8
Q
what do D1 cells secrete?
A
VIP
9
Q
what do enterochromaffin cells secrete?
A
serotonin
10
Q
what do alpha granules look like?
A
round, dense, w/ a thin halo
11
Q
what do beta granules look like?
A
crystalline core w/ a wide halo
12
Q
what do delta granules look like?
A
round, less dense core w/ a thin halo
13
Q
what do PP granules look like?
A
small, hyperdense cores
14
Q
what are the 2 main disorders of the pancreatic islet cells?
A
diabetes mellitus
AND
pancreatic endocrine tumors
15
Q
what is diabetes mellitus a dysfxn or loss of?
A
pancreatic BETA cells
16
Q
what are pancreatic endocrine tumors?
A
abnormal proliferation of pancreatic islet cells
17
Q
T/F: DM is a single disease entity
A
FALSE
it’s a group of metabolic disorders sharing hyperglycemia
18
Q
what does DM result from defects in?
A
insulin secretion
insulin action
or both
19
Q
what are chronic hyperglycemia & metabolic dysregulation assoc w/?
A
secondary organ damage, esp in kidneys, eyes, nerves, & BVs
20
Q
how many ppl are affected by DM?
A
> 20 million children & adults
>140 million people worldwide
21
Q
what is the leading cause of ESRD, adult-onset blindness, & non-traumatic lower extremity amputation?
A
DM
22
Q
how many adults are pre-diabetic?
A
54 million
23
Q
what is pre-diabetic?
A
elevated blood sugar not meeting criteria for dx of DM
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
25
what is the estimated lifetime risk of being diagnosed w/ DM if you were born in 2000 and you are female?
2 in 5
26
what is the estimated lifetime risk of being diagnosed w/ DM if you were born in 2000 and you are an ethnic minority?
2-5x higher in AA, hispanic, & native american communities (cp to non-hispanic egg whites)
27
what is the cost of DM in the US (in 2011)?
174 billion bucks yo
28
what region of the US is more affected by DM?
the DIRTY SOUTH
29
to be diagnosed w/ DM, you have to have (how many?) of 3 criteria
only 1
30
what are the 3 possible criteria for DM dx?
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
31
what is a NORMAL fasting blood sugar?
<100
32
what is a NORMAL glucose tolerance test blood sugar?
<140
33
what is type 1 DM?
an ABSOLUTE DEFICIENCY of INSULIN d/t AUTOIMMUNE destruction of beta cell mass
34
which cells are involved in the type 1 DM immune response?
t-lymphs mount an attack against pancreatic beta cell ag
35
what is type 2 DM?
PERIPHERAL RESISTANCE to insulin action
36
what happens w/ insulin in type 2 DM?
inadequate secretion by pancreatic beta cells creates a RELATIVE INSULIN DEFICIENCY
37
do 90-95% of diabetics have type 1 or type 2?
type 2
38
T/F: to have DM type 2, you have to be overweight
you don't HAVE to be
| but most ARE
39
which gene contributes over 50% of the susceptibility to DM1?
HLA locus on 6p21
40
what haplotypes do 90-95% of whites w/ DM1 have?
either HLA-DR3 or HLA-DR4
41
40-50% of DM1 pts have what genetic thing?
DR3/DR4 heterozygotes
42
which 4 non-HLA genes are involved in DM1?
1. insulin (VNTR)
2. CTLA4
3. PTPN22
4. CD25
43
what viruses can cause DM1?
```
mumps
rubella
coxsackie B
CMV
"others"
```
44
what are the 3 general ways that viruses can cause DM1?
bystander
molecular mimicry
precipitating virus
45
how does the "bystander" pathway work to cause DM1?
viral infection induces islet cell injury/inflammation > exposure to self beta cell ag > activation of autoreactive T cells
46
how does the "molecular mimicry" pathway cause DM1?
viral proteins mimic beta cell ag & the immune response cross-reacts
47
how does the "precipitating virus" pathway cause DM?
viral infection early in life could persist in tissue
| subsequent infection w/ a similar virus could elicit an immune response against infected islet cells
48
what happens prior to any signs & sx in DM1?
slow progressive destruction of beta islet cells
49
how many (%) of the beta cells have been destroyed before hyperglycemia & ketosis occur in DM1?
>90%
50
what is the fundamental immune abnormality in DM1?
failure of self-tolerance
51
what 3 env factors are involved w/ DM2?
sedentary lifestyle
diet
obesity
52
what is the concordance rate of DM2 in monozygotic twins?
35-60%
53
what doubles the lifetime risk of getting DM2?
if both parents are affected
54
what is the strongest gene association in DM2?
TCF7L2
55
is DM2 linked to HLA genes?
NOPE
| that's DM1
56
what are the 2 metabolic deficits of DM2?
1. insulin resistance
| 2. beta cell dysfxn (relative insulin deficiency)
57
what is insulin resistance?
decreased ability of peripheral tissues to respond to insulin
58
what is relative insulin deficiency in DM2?
inadequate insulin secretion in the face of hyperglycemia
59
what is the PRIMARY event in DM2?
insulin RESISTANCE
it predates hyperglycemia
and THEN you get beta cell dysfxn in increasing degrees
60
what 3 things does insulin do to adipose tissue normally?
INC glucose uptake
INC lipogenesis
DEC lipolysis
61
what 3 things does insulin do to striated muscle normally?
INC glucose uptake
INC glycogen synth
INC protein synth
62
what 3 things does insulin do to the liver normally?
DEC gluconeogenesis
INC glycogen synth
INC lipogenesis
63
what % of pts have visceral obesity?
80%
64
T/F: obese pts have insulin resistance w/o hyperglycemia
TRUE
| in states of fat XS, there is a fundamental abnormality in insulin signaling
65
in states of insulin resistance, what happens to insulin secretion?
it is initially higher for each level of glucose
66
what does hyperinsulinemic state compensate for in DM2?
peripheral insulin resistance
| so you can maintain normal blood glucose levels
67
what happens when beta cell compensation becomes inadequate?
you get diabetes
that sucks
a lot
68
what happens to the islet cells in DM2?
amyloid replacement
69
what is glucotoxicity?
persistent hyperglycemia
70
what is HGBA1C?
glycosylated hemoglobin (hb bound to glucose)
71
what is the BEST assessment of glycemic control?
HbA1C
72
how is HbA1C formed?
nonenzymatic covalent addition of glucose moieties to hemoglobin in RBCs
73
what is the time span for HbA1C?
120 days
| i.e. the lifespan of an RBC
74
what is the HbA1C in a non-diabetic?
<7%
75
when do advanced glycosylation end (AGE) pdts form?
when nonenzymatic rxns occur btwn glucose & the amino groups of intra & extracellular proteins
76
what can accelerate AGE formation?
hyperglycemia
77
what can AGE pdts cross-link to?
extracellular matrix proteins
78
what happens when AGE pdts cross-link extracellular matrix proteins?
DEC vascular elasticity
INC protein deposition
ENTRAP non-glycated plasma & interstitial proteins (LDL)
79
which tissues do not require insulin for glucose transport?
```
nerves
lenses
kidneys
BVs
(these are the tissues that are affected in diabetics)
```
80
what happens to nerves in hyperglycemic states?
diabetic neuropathy
| i.e. glucose neurotoxicity
81
what is the etiology of peripheral tissue damage d/t persistent hyperglycemia?
INC intracellular glucose in tissues that do NOT require insulin for transport > DEC glutathione pdtion > INC susceptibility to oxidative stress
82
what is macrovascular dz?
accelerated atehrosclerosis involving the aorta & large & medium arteries
83
what is a HALLMARK of DM?
macrovascular dz
84
what is the most common cause of death in DM?
MI d/t atherosclerosis of coronary arteries (equally common in M & F)
85
how can macrovascular dz manifest in a pt?
(besides MI & death)
| gangrene of lower extremities
86
what type of arteriosclerosis is assoc w/ HTN?
hyaline
87
what is microvascular dz?
diabetic microangiopathy
| diffuse thickening of the BM
88
where is microvascular dz most evident (MICRO is your hint)
capillaries
89
what is weird about diabetic capillaries?
they are leakier than normal to plasma proteins
90
what underlies the development of diabetic nephropathy, retinopathy, & some types of neuropathy?
microvascular dz
91
what is the 2nd most common cause of death in DM?
diabetic nephropathy d/t microvascular dz (MI d/t macrovascular was #1)
92
where do you get lesions in diabetic nephropathy?
glomerular lesions
&
renal vascular lesions (primarily arteriolosclerosis)
93
what are glomerular lesions?
capillary BM thickening (bc glomerular lesions are seen in diabetic nephropathy which is d/t microvascular dz)
94
what do ALL cases of diabetic nephropathy have?
glomerular lesions
95
what can you see on EM w/ glomerular lesions?
diffuse mesangiosclerosis
96
what does a kidney look like (gross) in a pt w/ nephrosclerosis & long-standing diabetes?
bumpy and gross and red
97
what can you see on PAS stain w/ glomerular lesions?
Kimmelsteil-Wilson nodules
98
what are the (6) oral manifestations of DM?
1. dental caries
2. salivary dysfxn & xerostomia
3. oral mucosal dz
4. oral infxn
5. gingivitis & periodontal dz
6. taste & other neurosensory disorders
99
what contributes to dental caries in DM pts?
diet
| decreased salivary flow
100
what oral mucosal dz can DM pts get?
lichen planus
| aphthous stomatitis
101
what oral infxn are DM pts prone to?
oral candidiasis
102
what does candidiasis look like?
white shit in your mouth
103
what does periodontal disease look like?
brown tooth borders (granulomatous tissue at gingival margin)
104
what pt group presents w/ DM1?
the young
105
what are the dominant clinical features of DM1 (there are 4)
polyuria
polydipsia
polyphagia
ketoacidosis
106
what does insulin deficiency result in?
catabolic state affecting glucose, protein, & fat metabolism
| insulin is a major anabolic hormone
107
what pt population should you suspect DM2 in?
older (>40 yo)
| obese
108
when is a dx of DM2 usu made?
after routine blood or urine testing in an asymptomatic pt
109
do DM2 pts get ketoacidosis?
yeah but it's infrequent bc higher portal vein insulin levels prevent unchecked FA oxidation & ketone body formation is restricted
110
what happens when DM2 is decompensated?
hyperosmotic nonketotic coma w/ severe dehydration from hyperglycemic polyuria
111
what do DM2 pts NOT develop?
N/V
respiratory sx
(these occur in keto)
112
what happens to the pancreas in DM1 (think histo)?
insulitis
beta cell depletion
islet atrophy
113
what happens to the pancreas in DM2 (think histo)?
amyloid deposition in islets
114
what are the most common pancreatic endocrine neoplasms?
neoplastic proliferation of beta cells
| i.e. INSULINOMAS
115
what do insulinomas do?
produce insulin!
116
can insulinomas cause clinical hypoglycemia?
YOU BETCHA
117
how do you differentiate acute hypoglycemia d/t INSULINOMA vs exogenous insulin injection?
insulinoma pts have INC INSULIN & C-PEPTIDE
118
what are the 3 types of rare pancreatic endocrine neoplasms?
alpha cell tumors
delta cell tumors
vipoma
119
what is another name for an alpha cell tumor?
glucagonoma
120
what is another name for a delta cell tumor?
somatostatinoma
