Endocrine Disorder 1/ Pancreatic Disorders Flashcards
1
Q
What are is the pancreas composed of?
A
two anatomically discrete sets of cells and functions
2
Q
What two types of cells make up the pancreas?
A
exocrine
endocrine
3
Q
What is the source of insulin and glucagon in the pancreas?
A
endocrine pancreas
4
Q
What cells make up the bulk of the pancreas?
A
exocrine
5
Q
What is the role of the exocrine pancreas?
A
secrete digestive enzymes into ducts that drain via the pancreatic duct and the common bile duct into the duodenum
6
Q
What is the exocrine pancreas?
A
glands lined with epithelial (acinar) cells
7
Q
What is in the endocrine pancreas?
A
islet of langerhans
8
Q
What is the purpose of endocrine pancreas?
A
insulin and glucagon
9
Q
What other hormones are excreted by the endocrine pancreas?
A
amylin, somatostatin, pancreatic polypeptide
10
Q
Where can tumors occur in the pancreas?
A
head of the pancreas
11
Q
What are the three major types of cells in the islet of langerhans?
A
alpha cells
beta cells
delta
12
Q
Why is the blood supply near the islet of langerhans?
A
since the islet of langerhans secrete insulin and glucagon the vasculature allows for immediate secretion into the blood stream
13
Q
What is the size of the islet of langerhans?
A
0.3mm in diameter
14
Q
How many islets of langerhans are in the human pnacreas?
A
1-2 million
15
Q
What do alpha cells secrete?
A
glucagon
16
Q
What do beta cells secrete?
A
insulin
17
Q
What do delta cells secrete?
A
somatostatin
18
Q
Why are the cells within the islet of langerhans located close together?
A
Their close proximity allows for a close negative feedback loop
insulin inhibits glucagon secretion, amylin inhibits insulin secretion, and somatostatin inhibits the secretion of both insulin and glucagon
19
Q
What is an example of a positive feedback loop?
A
oxytoxin during birth
20
Q
What results in insulin release?
A
carbohydrate ingestion
21
Q
What does insulin do when excess amounts of carbohydrates are consumed?
A
increases to store carbohydrates as glycogen in the liver
22
Q
What happens with the excess carbohydrates that can not be stored as glycogen?
A
They are converted under the stimulus of insulin into fats and stored in adipose tissue
23
Q
Define glycogenolysis
A
breaking down glycogen to glucose in the liver
glycogen breaks down into glucose 1 phosphate and glucose with hepatocytes
24
Q
Define Gluconeogenesis
A
utilizing fructose and galactose to glucose
glucose is synthesized from non-carbohydrate metabolites
25
What form does insulin circulate into the blood?
unbound
26
What is the plasma 1/2 life of insulin?
6 minutes
27
What enzyme degrades insulin and where?
insulinase in the liver
28
How does insulin facilitate glucose uptake?
enzyme linked receptor on target cells in varying tissues
29
When is glucagon secreted?
In response to decreased blood glucose levels
| opposite of insulin
30
What is the function of glucagon?
increase blood glucose concentration
31
Examples of hyperglycemic hormones
cortisol
growth hormone
epinephrine
glucagon (stimulates glycogenolysis/ glyconeogenesis and inhibits glycolysis)
32
How much does glucagon increase the blood glucose in the blood in what amount of time?
1mcg/kg of glucagon can elevate the blood glucose concentration approximately 20mg/100ml of blood (25% increase) in about 20 minutes
33
What affects does glucagon have on the liver (2)?
breakdown of liver glycogen (glycogenolysis)
| increased gluconeogenesis in the liver
34
What are four OTHER functions of glucagon?
enhances the strength of the heart (contractility)
increases BF to some tissues (esp. kidneys)
enhances bile secretion
inhibits gastric acid secretion
35
What is the half life of somatostatin?
3 minutes
36
Somatostatin has the same chemical substance as
growth hormone inhibitory hormone
37
What is is somatostain designed to do?
delay the time the body can absorb the nutrients in the stomach
extend the period over which the food nutrients are assimilated into the blood
38
What does somatostatin do in a variceal bleed?
it inhibits the secretions to decrease motility in the GI tract
39
When is somatostatin normally secreted?
ingestion of food stimulate secretion
40
What are 3 inhibitory effects of somatostatin?
depresses secretion of both insulin and gallbladder
| decreases motility of stomach, duodenum and gallbladder
41
What are majority of pancreatitis cases associated with?
gallstones or alcoholism
42
What does pancreatitis result from?
autodigestion and inflammation of the pancreas caused by inappropriate activated pancreatic enzymes
43
What is diabetes mellitus?
group of disorders with relative or absolute insulin deficiency
44
What does diabetes mellitus result from?
inadequate supply of insulin and/or inadequate tissue response to insulin
45
What lab levels will be increase in pancreatits?
amylase
| lipase
46
what does diabetes mellitus result in?
hormone induced metabolic abnormalities
microvascular and macrovascular lesions
long-term end organ complications
47
Describe the type 1 diabetes mellitus
autoimmune destruction of the pancreatic beta islet cells
48
Describe the type 2 diabetes mellitus
peripheral insulin resistance through multiple defects with insulin action and secretion
49
What is associated with type 1 DM?
15% associated with other autoimmune diseases (graves disease, hashimoto thyriditis, addison disease and myasthenia gravis)
50
How are plasma insulin levels in type 1 DM?
relatively low for the level of blood glucose (absence or minimal circulating levels)
51
What type of DM requires insulin therapy?
Type 1 DM
52
How does Type 1 DM result?
autoimmune related
| results from T cell mediated destruction of beta cells within pancreatic islets
53
What type of DM is 90% of cases?
Type 2
54
What is associated with type 2 DM?
associated with excessive weight gain in adults and pediatrics
55
How are plasma insulin levels in type 2 DM?
plasma insulin levels are normal or increased
56
What is type 2 DM prone to?
susceptible to hyperglycemic-hyperosmolar nonketotic state
57
How does Type 2 DM result?
not immune related
| results from defects in insulin receptors and postreceptor intracellular signaling pathways
58
What is type 1 DM susceptible to?
ketoacidosis
59
What are the common medications for diabetes?
```
acarbose
biguinades
dipeptidyl peptidase 4 inhibitors
glucagon like peptide 1 receptor agonists
meglitinide
sodium-glucose transport protein 2 inhibitors
sulfonylureas
thiazolidinediones
```
60
What is acarbose?
delay GI glucose absorption
61
What is an example of biguanides?
metaformin
62
What do biguanides?
suppresses excessive hepatic glucose release
63
What are examples of dipeptidyl peptidase 4 inhibitors?
sitagliptin
saxagliptin
vildagliptin
64
What are examples of glucagon-like peptide 1 receptor agonist?
albiglutide
dulagutide
exenatide
65
What are examples of meglitinides?
repaglinide or nateglinide
66
What is the MOA of sulfonylureas?
increases insulin availability (by stimulating insulin secretion from pancreatic beta cells; enhance insulin-stimulated peripheral tissue utilization of glucose
67
What is the MOA thiazolidinediones?
improves insulin sensitivity
68
What is the MOA of meglitinides?
increases insulin availability
69
What are examples of sodium-glucose transport protein 2 inhibitors?
canagliflozin or empagliflozin
70
What are are examples of sulfonylureas
glibenclamide
glipizide
glimepiride
71
When do insulin dependent patients experience an increase in insulin requirements? Why?
during the post midnight hours
| accelerated glucose production and impaired glucose use due to noctural surges in secretion of growth hormone
72
What is the BS of an insulin dependent patient in the early mornings?
hyperglycemia
73
What is the absorption of insulin dependent on?
highly variable and dependent on type of insulin, the site of administration, and subcutaneous blood flow
74
What are the 5 major risk factors for diabetic patients undergoing surgery?
cardiovascular
renal
joint collagen tissue abnormalities (limited neck extension)
neuropathies
infections complications and poor wound healing
75
What is more important with a patient with long standing diabetes perioperative?
degree of glucose control
| end-organ dysfunction that exists
76
What is glucotoxicity?
long term exposure to high blood glucose
nonenzymatic glycosylation reactions that lead to the formation of abnormal proteins which weaking endothelial junctions and decrease elastances
77
What are signs and symptoms of glucotoxicity
difficult intubations, decreased wound healing, tensile strength
glucose-induced vasodilation
78
What does glucose-induced vasodilation from glucotoxicity cause?
prevents target organs from protecting against increase in systemic blood pressure
renal failure in time
79
What varies in vascular beds?
the threshold for glycemic toxicity
| retinopathy vs coronary arteries
80
According to the WHO surgical safety checklist, what is the target BS ?
100-180mg/dL
81
How do you initiate insulin therapy for hyperglycemia?
bolus 5-10units IV
| divide the last serum glucose value by 150
82
What is the primary site of endogenous glucose production?
lvier
83
What are the precursors for gluconeogenesis?
pyruvate and lactate
| certain gluconeogenic amino acids and glycerol (from fat metabolism)
84
Discuss normal glucose physiology
eating
increased blood glucose
stimulate insulin secretion
stimulates glucose utilization in tissues
85
What occurs postprandial with glucose?
glucose utilization exceeds glucose production
transition from exogenous glucose delivery to endogenous production + decreased insulin secretion
= maintenance of a normal plasma glucose
86
Where is 70-80% of the glucose released by the liver metabolized?
insulin-insensitive tissues
| brain, GI tract, RBCs
87
What age does Type 1 diabetes present?
before age 40 in genetically susceptible individuals
88
what causes onset of type 1 diabetes?
sudden onset due to critical mass of loss of beta cells
89
How much beta cell function must be lost prior to hyperglycemia occurs?
80-90%
90
What are signs and symptoms of hyperglycemia?
```
fatigue
weight loss
polyuria
polydipsia
blurry vision
intravascular volume depletion
```
91
What is diagnoses of Type 1 DM based on
presence of random blood glucose >200mg/dL and a hemoglobin A1c >7%
92
If insulin is withheld in a DM1, what can occur?
diabetic ketoacidosis
93
What are characteristics of Type 2 diabetes?
relative beta cell insufficiency and insulin resistance
inherited insulin resistance
obesity and sedentary lifestyle are contributing factors
94
Describe the initial pathological insult in type 2 DM
peripheral tissues (skeletal muscle, adipose tissue, liver) become insensitive to insulin leads to an increase in pancreatic insulin secretion (hyperinsulinemia) to maintain normal plasma glucose
95
Describe the progression of DM2
pancreatic cell function decreases, and insulin levels are unable to compensate and hyperglycemia occurs
96
What are the three main defects of DM2
increased rate of hepatic glucose release
impaired basal and stimulated insulin secretion
inefficient use of glucose by peripheral tissues
97
What syndrome is seen with DM2 patients?
metabolic syndrome
98
What does metabolic combine insulin resistance with
```
hypertension
dyslipidemia
procoagulant states
obesity
premature atherosclerosis/ cardiovascular disease
```
99
Diagnosis of DM according to the American diabetes association,
fasting (no caloric intake for > 8hrs) plasma glucose .126mg/dl
random plasma glucose concentration >200mg/dL
2-hour plasma glucose level > 200mg/dL during an oral glucose tolerance test
100
What is an impaired fasting glucose?
101-125mg/dL
101
What does an hemoglobin A1c provide?
valuable measure of long term glycemic control
102
What is a normal HbA1c?
4-6%
103
What does glucose do to a hemoglobin molecule?
nonenzymatically glycosylated
104
What is the importance of glycosylated hemoglobin?
freely crosses the RBC membrane and is directly proportional to average plasma glucose concentration during the preceding 60-90 days
105
What is the first line treatment of DM2?
weight loss and exercise therapy
106
How does weight loss and exercise therapy help with DM2
decreases adiposity improves hepatic and peripheral tissues insulin sensitivity, enhances post-receptor insulin action and may possibly increase insulin secretion
107
How is pharmacologic therapy of DM2 managed?
titrated to achieve fasting and peak postprandial glucose levels recommended by the ADA
108
What are the common pharmacologic therapies for DM2?
sulfonylurea or biguanide
109
What is added to a DM2 regimen if combination oral therapy is unsuccessful?
a bed time dose of intermediate-acting insulin
110
Why is an intermediate acting insulin added at night for DM2?
hepatic glucose overproduction is typically highest at night
111
When is a DM2 patient switched to insulin therapy alone?
if oral agents plus single dose insulin therapy isn't effective
112
What are the 4 kinds of insulin?
```
basal insulin (intermediate acting and administered twice daily)
long acting (administered once daily)
short acting (regular) (provide glycemic control at meal times)
rapid acting (provide glycemic control at meal times)
```
113
What is a typical insulin requirement/ regimen for a DM1?
0.5-1u/kg/day divided into multiple doses with 50% given as basal insulin
114
What is diabetic ketoacidosis?
high glucose levels exceed the threshold for renal tubular absorption causing significant osmotic diuresis with marked hypovolemia
115
When does ketosis occur?
when the carbohydrate intake is low
116
How are ketones produced?
When the body breaks down fat it produces an acid, ketones or ketone bones
117
What becomes the body's main source of energy in hyperglycemia/DKA?
ketones
118
What does the increase in ketoacids create?
anion-gap metabolic acidosis
119
Hepatic ketogenesis leads to
overproduction of ketocaids in the liver
120
What labs are seen in DKA
hypokalemia
hyponatremia
hypophosphatemia
121
How does hyponatremia occur in DKA
results from the effect of hyperglycemia and hyperosmolality on water distribution (dilutional)
122
How does hypokalemia occur in DKA
```
usually substantial (3-5meq/l) as moves into the intracellular space with insulin as the acidosis is correct
K also excreted in urine b/c of the increased delivery of sodium to the distal renal tubules that accompanies volume expanison
```
123
How does hypophosphatemia occur in DKA
result of tissue catabolism, impaired cellular uptake and increased urinary losses and can lead to diaphragmatic and skeletal muscle dysfunction and impaired myocardial contractility
124
What is the treatment for DKA?
normal saline
IV loading dose of 0.1u/kg of regular insulin plus a low dose insulin infusion of 0.1 u/kg/h
caution with correction of hyperglycemia without simutaneous correction of serum sodium-> can lead to cerebral edema and seizures
correct electrolytes
125
What is hyperglycemic hyperosmolar syndrome?
severe hyperglycemia, hyperosmolarity and dehydration
126
S/S of HHS
```
polyuria
polydipsia
hypovolemia
hypotension
tachycardia
organ hypoperfusion
```
127
What is responsible for mental obtundation or coma in HHS?
hyperosmolality
| >340mOsm/L
128
If a DM patient presents with metabolic acidosis what is a difference between DKA and HHS?
ketoacidosis (only in DKA)
129
What is the treatment of HHS?
large volumes of hypotonic saline (1000-1500ml/h) should be administered until the osmolarity is <320mOsm/L then isotonic saline (1000-1500ml/h)
IV bolus of 15 U of regular insulin followed by a 0.1u/kg/hr infusion
less severe electrolyte deficits then DKA
130
What are complications of diabetes?
```
nephropathy
peripheral neuropathy
retinopathy
autonomic neuropathy (tachycardia/ST elevation)
cardiovascular disease
```
131
What can reduce the development ad progression of additional comorbidities in DM
strict glycemic control and blood pressure control
132
What are 3 newer treatments of DM
implanted (like a pacemaker) glucose analyzer with electronic transmission to a surface (watch) monitor
new islet transplantation medication
INGAP (islet neogenesis-associated protein) peptide
133
What does INGAP do?
may cause regrowth of normally functioning islet cells
134
What does the islet transplantation medications do:?
make islet cell transplants more successful and rejection medication less hazardous
135
How is hypoglycemia caused in a non-diabetic patient?
```
pancreatic islet cell adenoma or carcinoma
large hepatoma
large sarcoma
alcohol ingestion
use of various medications
```
136
What is hypoglycemia
plasma glucose level <50mg/dl
137
What are symptoms of hypoglycemia?
adrenergic (sweating, tachycardia, palpitations, restlessnes, pallor) and neuroglycopenic (fatigue, confusion, headache, somnolence, convulsions, coma)
138
What is the treatment for hypoglycemia?
dextrose 0.5-1g/kg IV/IO
139
What % dextrose for adults?
50
140
What % dextrose for pediatrics
25
141
What % dextrose for neonates
5-10
142
What is an insulinoma?
rare benign insulin secreting pancreatic islet cell tumors
143
What can an insulinoma present as
multiple endocrine neoplasia syndrome tpye 1
144
What is the triad for MEN 1?
insulinoma
hyperparathyroidism
pituitary tumor
145
Diagnosis of insulinoma
whipple's triad
symptoms of hypoglycemia with fasting
a glucose level below 50 with symptoms
relief of symptoms with administration of glucose
146
What confirms an insulinoma?
inappropriately high insulin level (>5-10mu/ml) during a 48 to 72 hour fast confirms the diagnosis
147
What medication will a patient with an insulinoma be taking preoperatively?
diazoxide
| directly inhibits insulin release from beta cells
148
Does the surgical treatment for insulinoma curative?
yes
149
How frequently are you checking BS during an insulinoma removal?
q15minutes
150
What will BG levels be intraoperatively with an insulinoma?
hypoglycemia with tumor manipulation
| hyperglycemia following tumor removal
151
What medications can be used intraoperatively with an insulinoma?
somatostatin analogue octreotide
| suppress insulin release from such tumors
152
What needs to be in fluids after insulinoma removal?
glucose to MIVF
