Diabetes Pancreatitis Flashcards
What are the exocrine functions of the pancreas?
Acinar cells secrete pancreatic enzymes into pancreatic duct
What are the endocrine functions of the pancrase?
IN
islets of langerhan cells secrete hormones into the blood vessels
What are the digestive functions of the exocrine pancreas?
Secretes alkaline fluid containing bicarbonate and digestive enzymes that assist in absorption of nutrients and digestion in the small intestine
What enzymes are produced/secreted by acinar cells?
– Amylolytic enzymes:
• Hydrolyze starch
• AMYLASE
– Lipolytic enzymes:
• Include LIPASE,phospholipaseA2,cholesterolesterase
– Proteolytic enzymes:
• ELASTASE,trypsin,chymotrypsin,carboxypeptidases,aminopeptidases
What are hte multiple hormones that the endocrine pancreas makes to regulate glucose homeostasis?
insulin
glucagon
somatostatin
insulin (HIGH GLUCOSE)
glucose stimulates BETA cells to secrete insulin
glucagon (LOW GLUCOSE)
low insulin/blood glucose stimulates ALPHA cells to produce glucagon that stimulates glycogenolysis/gluconoeogenesis
somatostatin
deta cells –> STT –> inhibits both insulin and glucagon secretion
How is hte insluin molecule formed?
Preproinsulin (contains signal peptide and c peptide) >
pro insulin (c peptide) >
insulin (just A and B chains)
Describe insulin biogenesis?
Reserve pool and RRP
What happens when insluin is realsed from readily releasable pools followed by reserve pools?
biphasic insulin release
What counterregulates glucose when it is low (sxs seen when glucose is < 55)?
Glucagon epinephrine growth hormone cortisol imparied cognition
A 45 year old female nurse presents to the ER with confusion, palpitations and diaphoresis.
• Labs:
– Random plasma glucose: 40 mg/dL
What is the definition of hypoglycemia?
• Depends on whether the patient has diabetes
• In diabetics:
– ADA recommended there should be concern about the
possibility of hypoglycemia if ≤ 70 mg/dL
– Higher than cut‐off for non‐diabetics, reflecting concern that diabetics may have repeated hypoglycemic episodes related to treatment
• In non‐diabetics:
– Hypoglycemia should not be diagnosed solely on the basis of a glucose level unless it is severely depressed (<40 mg/dL
– That being said, symptoms usually kick in for non‐diabetics ≤ 55 mg/dL
– Only patients with Whipple’s triad should be evaluated for a hypoglycemic disorder
What is whipple’s triad?
Whipple’striad: Whipple triad is the clinical presentation of PANCREATIC INSULINOMA and consists of:
1. fasting hypoglycemia (<50 mg/dl)
2. symptoms of hypoglycemia
3. Immediate relief of symptoms after the administration of IV glucose.
– Recognize that the patient’s symptoms could be caused by hypoglycemia
– Document that the patient’s plasma glucose concentrations are low when the symptoms are present
– Show that the symptoms can be relieved by administration of glucose
• If it is possible, order a 2nd random plasma glucose before glucose infusion to confirm result
– However if clinical situation is urgent do NOT delay glucose infusion for a second measurement
What is the most common ddx for hypoglycemia?
• Diabetes mellitus
– Due to exogenous insulin or an insulin secretagogue (i.e. sulfonylurea or glinide)
• Drug induced
– MOST common cause of hypoglycemia
– 164 drugs associated with hypoglycemia
– Seen with quinolones, pentamidine, quinine, beta blockers, ACE inhibitors, IGF‐1, others
– Alcohol:
• Inhibits gluconeogenesis but not glycogenolysis
• Typically happens after a several‐day binge with limited food ingestion resulting in hepatic glycogen depletion
What are less common causes of hypoglycemia?
• Endogenous hyperinsulinism: – Insulinoma
– Sulfonylurea/glinide use
– Nesidioblastosis
– Insulin autoimmune hypoglycemia
• Antibodies to insulin or insulin receptor
• Accidental, malicious or surreptitious hypoglycemia:
– Suspect with children (Munchausen’s by proxy), health care workers,
spouses of diabetics, pharmacy or medical error • Pseudohypoglycemia:
– Ifcollectiontubedoesnothaveaninhibitorofglycolysis,glucosecan lower by 10 mg/dL per hour in the tube
– Shouldbemeasuredfromagray‐toptube(withNaF) • Other:
– Non‐islet cell tumors, cortisol deficiency, malnourishment, critical illness
After Whipple’s triad is confirmed, what additional tests should be ordered, and why?
Additional tests: – Insulin – C‐peptide – Proinsulin – Sulfonylurea and glinide screen – Beta‐hydroxybutyrate
•Once patient is treated and asymptomatic, she should undergo a supervised fast until symptom recurrence, or until 72 hours elapse
How do you interpret these lab results measured during a 72 hour fast?
• Glucose 40 mg/dL
• Insulinlevel: 12mU/L
– Reference range: up to 20 mU/L when fasting
– However, if glucose < 55 mg/dL insulin should be < 3 mU/L
• C‐peptidelevel: 2.9ng/mL
– Reference range: 0.8‐4 ng/mL when fasting
– However, if glucose < 55 mg/dL, C‐peptide should be < 0.6 ng/mL
• ThereforebothinsulinandC‐peptideare inappropriately normal (high for the situation)
What causes endogenous hyperinsulinemia?
- Sulfonylurea/glinide use
- Insulinoma
- Autoimmune hypoglycemia mediated by insulin antibodies
- Noninsulinoma pancreatogenous hypoglycemia syndrome
- Post gastric bypass hypoglycemia
Insluinoma -elevated insluine and high c peptide
What is seen with exogenous hyperinsulinemia?
elevation of insulin level and low c peptide
What are hte current diagnostic criteria for diabetes?
- Fasting plasma glucose ≥ 126 mg/dL
- HbA1C ≥ 6.5%
- 2 hour value in an OGTT ≥ 200 mg/dL
- Random plasma glucose concentration ≥ 200 mg/dL with symptoms
Does repeat testing of this patient’s plasma glucose need to be performed to confirm a diagnosis of diabetes? Why or why not?
- if the pt has unequivocal symptomatic hyperglycemia a subsequent measurement is NOT required
- in the absence of CLEAR SXS a repeat test is required
- if two different tests (RPG and A1C) are available then concordant repeat testing is NTO required regardless of sxs
- if two tests are discordant the test that is diagnostic of diabetes shoiuld be repeated to confirm the diagnosis
Which of the diagnostic criteria are now primarily recommended for the diagnosis of diabetes?
A1C > 6.5%
Diabetes should be confirmed w/ repeat A1c uncless CLEAR sxs or 2nd test concordant
What are the advantages of A1C?
increased convenience
correlation w/ retinopathy (increased w/ A1c > 5.5%)
HbA1C is indicative of glucose control over what time period?
Hgb undergoes nonenzymatic glycation
Reflects mean blood glucose over the entire 120 day life span of RBC but correlates best with the mean blood glucose over 2-3 mo period
What other laboratory tests can be used as indicators of glucose control over a period of time?
Fructosamine
1,5- anyhydroglucitol
What is fructosamine
albumin also undergoes nonezymatic glycosylation
fructosamine is formed when glucose reacts w/ amino terminus of albumin
turnover is in 28 days so reflects blood glucose over 1-2 week period
What is 1,5 anhydroglucitol?
renal absorption is inhibited by blood glucose, reflects blood glucose over last 24 hrs
When are HbA1C results not reliable?
• Hemoglobinopathies:
– If a patient has no hemoglobin A (SS, SC, EE) then they will not have HbA1c
• Hemolysis:
– Life span of RBCs shortened which will falsely
lower HbA1c values
• Polycythemia or post‐splenectomy:
– Somewhat longer life span of RBCs will falsely elevate HbA1c
• Fructosamine is recommended alternative test
A 65 year old diabetic female is brought to the ER after being found unresponsive at home.
• Labs:
– Random plasma glucose = 650 mg/dL
iven her known history of diabetes, what two entities are of greatest concern given her clinical presentation and glucose level?
Diabetic ketoacidosis or hyperosmolar hyperglycemic state (HHS)
What laboratory tests should be ordered to differentiate between DKA and HHS?
- Serum glucose
- Serum electrolytes
- UA with urine ketones by dipstick
- Plasma osmolality
- Serum ketones (if urine ketones present)
- Arterial blood gas (if urine ketones or anion gap present)
How do you differentiate DKA from HHS?
DKA: glucose <800 more likely w/ type 1 rapid over 24 hrs < 65 ketones PRESENT
HHS: glucose > 1000 more likely w/ type 2 isidious w/ polydipsia, polyuria, weight loss >65 ketones ABSENT
*Interesting factoid: It has been hypothesized that ketone bodies are not generated in HHS because these patients tend to have some insulin which can block lipolysis. The amount of insulin required to block lipolysis is 1/10 what is required for glucose utilization, so the insulin blocks lipolysis but can’t stimulate glucose utilization leading to hyperglycemia.
Given the following lab results, what is the most likely diagnosis:
pH 7.18 (7.35‐7.45) [HCO3] = 11 mEq/L (20‐32)
anion gap = 20
Diabetic ketoacidosis. The ketones are organic acids that create a high anion gap metabolic acidosis. The bicarbonate is low to compensate for the acidosis. Urine and serum ketones would be positive if measured.
Given the following lab results, what is the most likely diagnosis:
pH 7.4 (7.35‐7.45)
[HCO3] = 23 (20‐32)
serum osm 330 mOsm/kg (nl 285‐295 mOsm/kg)
Hyperosmolar hyperglycemia state
What is the difference between serum osmolality and serum osmolarity and does it matter?
- Osmolality is the number of moles of solute in a kg of H2O (solvent)
- Osmolarity is the number of moles of solute in a liter (volume) of H2O (solvent)
- Osmolality is preferred as the mass of H2O is constant, whereas the volume of H2O can change with temperature
- However, overall these terms are often used interchangeably because the changes in volume of water with temperature are negligible
What is the formula for calculating serum osmolality?
Serum osmolality = 2Na+ + (glu/18) + BUN/2.8
How does one calculate an osmolar gap?
Osmolar gap = Measured osmolality – calculated osmolality
Normal gap <10 mOsm/kg
Would you expect an osmolar gap in patients with HHS, why or why not?
you would NOT expect an osmolar gap with HHS b/c glucose is in the equation for calcluated osmolality
What are causes of an increased osmolar gap?
Nonelectrolyte solutes such as ethanol, ethylene glycol, methanol, mannitol, acetone, isopropyl alcohol
What is the formula for calculating anion gap?
Anion gap = Na+ – (Cl‐ + HCO3‐)
– Normal gap: 3‐14 mmol/L
– Anion gap is used in an attempt to identify the cause of a metabolic acidosis (lower than normal pH in the blood) if the gap is greater than normal
What are causes of an increased anion gap?
MUDPILES – methanol, uremia, diabetic ketoacidosis, paraldehyde/propylene glycol, isoniazid, lactic acidosis, ethylene glycol, salicylates
A 32 year old female at 25 1/7 weeks gestation presents for gestational diabetes screening
What is the recommended screening approach for gestational diabetes?
• ADA and WHO recommend a 1 step approach
– 75 gram 2 hour oral GTT
– Requires a single elevated value for diagnosis
• ACOG recommends a 2 step approach
– Initial screening glucose challenge
– 3 hour oral GTT in screen positive patients
– In the United States the ACOG approach is the most commonly used
What are the advantages and disadvantages of each screening approach?
1 step approach
– Pros:
• Only 1 visit required for diagnosis
– Primarily what is used outside of the United States
• Simpler results interpretation – diagnosed with one abnormal value
– Cons:
• Implementation would increase diagnosis of GDM 2‐3 fold
• 2 step approach – Pros:
• Labeling of additional women with GDM will result in increased medical interventions and costs
• Current long‐standing practice in the United States
– Cons:
• One Canadian study showed only 36% of women with a failed screen received the 3 hour GTT
What is the 1 hour glucose screening challenge?
• 50 gram glucose load given
– Non‐fasting
• Glucose = 161 mg/dL (60‐130 mg/dL)
How is the 3 hour GTT performed, and what constitutes a positive GTT?
- Patient has fasting glucose measured
- 100 g glucose drink administered
- Measure plasma glucose at 1 hr, 2 hr and 3 hr
- Positive if 2 or more glucose values elevated
What are acceptable results of a 3 hour GTT
- Fasting: 75 mg/dL (60‐94 mg/dL)
* 1 hour: 132 mg/dL (60‐179 mg/dL) • 2 hour: 138 mg/dL (60‐154 mg/dL) • 3 hour: 137 mg/dL (60‐139 mg/dL)
How many patients fail the glucose screen? How many patients with a positive glucose screen end up with a diagnosis of gestational diabetes?
- Depending on the cut‐off used, 14‐23% of patients will fail the glucose screen
- Studies show that only 8‐11 % of patients who fail the initial screen will be diagnosed with gestational diabetes
What laboratory tests are recommended in a patient with acute right upper quadrant/epigastric pain?
- CBC
- Electrolytes, BUN, creatinine, glucose
- ALT, AST, alkaline phosphatase, bilirubin • Lipase
Labs: – HCG: negative – Total bilirubin: 3.4 mg/dL [0.2 – 1.3 mg/dL] – Alkaline phosphatase: 178 U/L [40 – 150 U/L] – ALT: 464 U/L [0 – 50 U/L] – AST: 245 U/L [0 – 45 U/L] – Lipase: 47,534 U/L [73 – 393 U/L] – WBC: 18.8 x 10e9/L [4 – 11 10e9/L] – Glucose: 135 mg/dL [70 – 99 mg/dL]
Based on these lab results, what is the most likely diagnosis?
Acutepancreatitis
• Diagnosis established with 2 out of 3 of the following criteria:
– Typical abdominal pain in the epigastrium that may radiate to the back
– 3x or greater increase in serum lipase and/or amylase
– Confirmatory findings of pancreatitis on abdominal
imaging
• NOcorrelationbetweenseverityofpancreatitis and degree of elevation of lipase/amylase
What other lab abnormalities can be seen in patients with acute pancreatitis?
• Elevatedamylase
• Leukocytosisandhyperglycemiaarefrequently seen
• Hemoconcentration with Hct > 44%
– May be a harbinger of more severe disease
• Azotemia(BUN)isasignificantriskfactorfor mortality
• Hyperbilirubinemia in ~10% of patients
• Transientelevationsofalkphos,ALT,AST
• Hypocalcemiain~25%
• Hypoxemia in 5 – 10% of patients
Why was amylase not on the list of recommended laboratory tests for this patient?
- Lipase elevations occur earlier and last longer than amylase
- amylase may be normal in 20% of pts with alcoholic pancreatitis and 50% of hypertrig associated pancreatitis
- amylase is NOT specific to the pancreas (salivary isoform, elevated in other conditions)
bottom line: measure lipase ALONE
What is macroamylasemia?
- Macroamylase is a high molecular weight form of amylase in the patient’s serum
- Typically this is due to binding of an immunoglobulin to amylase in the circulation
- The large size of this complex prevents excretion in urine leading to elevated amylase
- This elevated amylase is not diagnostic for nor related to pancreatitis
- Found in 1.5% of the nonalcoholic general adult hospital population
- Specialty labs can test for the presence of macroamylase if a patient has elevated amylase unrelated to pancreatitis
What are other causes of an elevated lipase?
– Acute or chronic pancreatitis – Post‐ERCP/trauma – Diabetic ketoacidosis – HIV – Macrolipasemia – Celiac disease – Drugs – Idiopathic – Renal failure – Acute cholecystitis – Bowel obstruction/infarction – Duodenal ulceration – Pancreatic stone/tumor
What are the most common causes of acute pancreatitis?
– Gallstones • 30 – 60% of cases – Alcohol • 15 – 30% of cases – Hypertriglyceridemia • 1 – 4% of cases; triglycerides usually > 1000 mg/dL – ERCP • occurs in 5‐10% patients post procedure – Drugs – Trauma or postoperative
What are some of the differences between acute and chronic pancreatitis?
Acute: non progressive painful lipase/amylase always elevated diffuse pancreas involvement with neutrophillic response
Chronic:
progg inflammatory changes w/ permanent damge
can be asymptomatic or have sxs of pancreatic insufficiency
amylase/lipase can be normal
patcy focal disease w/ mononuclear infiltrate and fibrosis
how is chronic pancreatitis diagnosed?
Diagnosis of early or mild chronic pancreatitis challenging due to lack of a biomarker for disease
– Amylase and lipase are not diagnostic or prognostic for chronic pancreatitis
• Triad of pancreatic calcifications, steatorrhea and diabetes mellitus are strongly suggestive, but are usually seen only in very advanced disease
• May have elevated bilirubin and alkaline phosphatase if there is cholestasis from common bile duct stricture due to chronic inflammation
• Steatorrhea:
– Indicative of pancreatic exocrine dysfunction if small bowel
biopsy normal
– 72 hour quantitative fecal fat is the gold standard
• Exocrine dysfunction:
– Most use fecal elastase, with values < 100 mcg/g strongly suggests severe pancreatic insufficiency
What imaging is used to diagnose chronic pancreatitis?
• Plain films, ultrasonography or CT scan can be used to identify calcifications, dilated ducts, atrophy, and also for excluding pseudocyst and cancer
• MRCP is becoming a diagnostic test of choice
– Can visualize calcifications and duct obstruction consistent with chronic
pancreatitis
– No contrast agents needed (MR sequence is sensitive to static fluid)
– Non‐invasive (unlike ERCP)
• Endoscopic ultrasound or ERCP
• Pancreatic function testing
– SECRETIN STIMULATION test has the best sensitivity and specificity amongst imaging options
– Secretin administered via IV, and duodenal aspirates collected at multiple time points
– Measureeitherbicarbonateorenzymesintheaspiratetodiagnosis pancreatic insufficiency
