Chapter 24- Endocrine Pancreas Flashcards
What is the process of insulin release
1) GLUT2 take glucose into the cells
2) Glucose generates ATP
3) ATP inhibits the membrane potassium channels
4) Depolarization results in calcium influx
5) Calcium influx causes insulin release
What are the locations that Islets of Langerhans are located
Neck and tail of pancreas
What is the effect of insulin on the adipose tissue
Increased glucose uptake
Increased Lipogenesis
What is the effect of insulin on striated muscle
Increased glucose uptake
Increased glycogen synthesis
Increases protein synthesis
What is the effect of insulin on the liver
Increased glycogen synthesis
Increased lipgenesis
Decreased gluconeogensis
What is the serum marker that is indicative for endogenous insulin
C peptide, as it is only created which insulin is cleaved into its activated form.
*Can be used to differentiate synthetic and endogenous insulin
What causes the release of incretins
Oral glucose
What are the incretins
- Glucagon like peptide-1 (GLP-1)
- Glucose dependant insulin releasing polypeptide (GIP)
What is the mechanism of action for incretins
Stimulate insulin release and inhibit glucagon release, resulting in a lower blood sugar level
What is the role of dipeptidyl peptdidase 4 (DDP-4) on incretin levels
Inactivate incretins, so the blood glucose level will rise
What is the significance of DDP on potential diabetes treatment
By blocking DDP4, there will be less incretin breakdown. As a result, there will be more blood glucose uptake and a reduction in the serum blood levels
What is the major gene linking to T1D
MHC class 2 on chromosome 6p21
How much of the pancreas must be destroyed to see T1D symptoms
> 90%
What are the major risk factors for T2D
- First degree relatives, so there is a familial aspect
- Obesity
What is are the characteristics of maturity onset diabetes of the young (MODY)
T2D like, but in the young:
- Increased blood insulin
- No Autoantibodies
- NOnketotic
What is the genetic link to MODY
Mutations resulting in the loss of function in glucokinase
When is the time to scan for gestation DM
- At the time of initial visit
- Second visit, at 24 to 28 weeks gestation.
What is the triad for diabetes
- Polyphagia (eating more)
- Polyuria (peeing more)
- Polydipsia (drinking more)
How is T2D usually identified on screening in children
- Fatigue or vision changes
- Increased thirst and urination
- Extreme hunger
- Weight loss
- Irritability of behavior changes
- Fruity smelling breath
What is the HLA typing for T1 or T2D
HLA DQ/DR on chromosome 6
What is a large deciding factor on T1 or T2DM
Presence of autobodies
How does the level of antibodies in T1D different between races
- Present in >90% of Caucasian children
- Present in < 50% of African American and Hispanic children
Diabetic ketoacidosios is more commonly seen in which form of diabetes
Type 1
What is the triad of diabetic ketoacidosis
- Hyperglycemia
- Ketonemia
- Metabolic acidosis
What are the common causes of diabetic ketoacidosis
- Noncompliance*** most common
- Precursor infections such as pneumonia and UTI
How to test for ketones
IN the urine
What are the usual clinical presenting signs from DKA
- Nausea/Vomiting
- Tachycardia
- Kussmaul respiration’s
What is Hyperglycemic hyperosmotic syndrome (HHS)
Acute hyperglycemic crisis in T2DM
What are the presenting features for HHS that differentiation for DKA
- Hyperglycemia (>600)
- Severe dehydration
- Hyperosmolaloty (can cause coma)
- Impaired renal function
- NO KETONESSS****
What is the most common cause of death in diabetics
Myocardial infarction
What are diabetics at a higher risk for
- Stroke
- MI (2x)
- Lower extremity gangrene (100x)
What are the major complications of diabetes in the eye
Retinopathy, cataracts, glaucoma
What are the major complications of diabetes in the kidney
Nephropathy
What are the major complications of diabetes with neuropathy
Pain, numbness, feet wounds and gangrene
What are the major complications of diabetes in the brain
TIA, cognitive impairment
What are the effects of advanced glycated end products
- Cytokines (TGF-Beta, VEGF)
- Reactive oxygen species
- Procoagulation
- Proliferation of smooth muscle
- cross linking of matrix proteins (proatherogenic)
What is the leading cause of end stage renal disease in the US
-Diabetic nephropathy
What are the three leasions seen during diabetic nephropathy
- Glomerular sclerosis
- Renal vascular lesions
- Pyelonephritis
What is the happening during the glomerular sclerosis as a result of diabetic nephropathy
-Thickening of the basement membrane and disruption of the cross linkages that make the membrane a filter
What are the pathological changes seen in diabetic nephropathy
- Early basement membrane thickening
- Kimmelstiel-Wilson disease (Nodular mesangial matrix accumulation in glomerulus)
What is the gold standard for testing for diabetic nephropathy
Urine albumin testing (UACR), as the first sign on diabetes is protein in the urine due to loss of filter function
What are the physical changes seen during diabetic retinopathy
- “Cotton wool” spots
- Hemorrhages and aneurysms
**Due to the neovascularization
What is the process that diabetes causes retinopathy
Neovascularization due to hypoxia leading to increased VEGF and blood vessels
What are some of the eye conditions that are seen as a result of diabetes
- Cataracts
- Glaucoma
Which infections are diabetics at a higher risk for
- Cellulitis
- Pneumonia
- Pyelonephritis
Which portion of the pancreas are at a higher risk for pancreatic neuroendocrine tumors
Neck and tail
What are the histological findings for a pancreatic neuroendocrine tumor
-Well differentiated with secretory granules
What type of cell tumor and rate of metastasis in an insulinoma
Beta cell with 10% metastasis
What type of cell tumor and rate of metastasis in an gastrinoma
G cells with 60% metastasis
What type of cell tumor and rate of metastasis in an somatostatinoma
Delta cell with 80% metastatic rate
What type of cell tumor and rate of metastasis in a glucagonoma
Alpha cell with 60% rate of metastasis
What type of cell tumor and rate of metastasis in an VIPoma
D1 cell with 80% rate of metastasis
What is the common histological finding in insulinoma
Amyloid
What are the characteristics of the a insulinoma
- Small tumors causing hypoglycemia
- C peptides levels are used to make the diagnosis
What are the symptoms, aka the triad of gastrinoma
Aka Zollinger ellison syndrome:
- Islet cell tumor
- Gastric acid hypersecretion
- Peptic ulceration
How are gastrinomas usually found
Ulcers that do no respond to the normal therapy
What is the triad of a somatostatinoma
- Diabetes
- Cholithiasis
- Steatorrhea
What is the cause of the triad that is normally seen in a somatostatinoma
- Reduced insulin (diabetes)
- Reduced gallbladder motility (gallstone)
- Reduced exocrine pancreatic secretions (steatorrhea)
What are the clinical presentations of a glucagonoma
4 D’s
- Diabetes
- Dermatitis (necrolytic migratory erythema in groin or LE)
- Depression
- DVTs
What are the clinical presentations of a VIPoma
WDHA syndome:
- Watery diarrhea
- Hypokalemia
- Achlorhydria
*Can also result in flushing in 20%
