What are the three anatomical regions of the pancreas?
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Head, body, tail of pancreas
2
From which week does the pancreas begin developing?
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Week 4
3
What is the origin of the pancreas and when does it start secreting insulin?
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- ventral bud and dorsal bud with endoderm origin
- secreting insulin from W10
4
What are the endocrine functions of the pancreas?
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- secretes hormones into the bloodstream
- α- and β-cells producing insulin and glucagon → regulate blood sugar levels
5
What are the exocrine functions of the pancreas?
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- 90% of its functions as an exocrine gland
- producing digestive enzymes
6
What is the building block of the exocrine pancreas?
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The acinus
7
What are acinar cells responsible for?
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Enzymatic secretions:
- Synthesize pancreatic enzymes
- store zymogens in secretory granules
8
What are ductal cells
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produce aqueous secretions in the pancreas and help neutralize acidic stomach contents
9
What are the zymogens secreted by acinar cells for protein digestion?
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Trypsinogen, chymotrypsinogen, and procarboxypeptidase.
10
What is the role of enterokinase in protein digestion?
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protease found in the duodenum that activates trypsinogen to yield trypsin
• Activated trypsin activates chymotrypsinogen and procarboxypeptidase
• yields chymotrypsin and carboxypeptidase
11
Acinar cell role in carbohydrate digestion
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pancreatic amylase, secreted in the active form
12
Acinar cell role in lipid digestion
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pancreatic lipase, secreted in the active form
13
Acinar role in nucleic acid digestions
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deoxyribonucleases and ribonucleases are produced to
digest the DNA and RNA, respectively
14
What is the role of bicarbonate in pancreatic ductal cell secretions?
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Bicarbonate neutralizes gastric acid and provides an optimal pH for pancreatic enzymes to function.
15
How do chloride and bicarbonate concentrations in ductal secretions vary with pancreatic flow rate?
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high flow rates: Higher bicarbonate and lower chloride
16
What are the three phases of pancreatic secretion regulation?
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- cephalic phase via vagal stim
- gastric phase via vagal stim and secretin
- intestinal phase via CCK, secretin, and vagal stim
17
What is the strongest stimulator for pancreatic secretions?
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Intestinal phase
• CCK = major for enzyme rich secretions
• secretin = water and bicarbonate
18
What is the multiplicative effect in pancreatic secretion?
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total secretion is greater than the sum of the secretions caused by each stimulus separately
- combined effects of multiple basic stimuli > sum of their individual effects
19
What is the inhibitor of pancreatic secretion?
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peptide YY
- secreted by neuroendocrine cells in the ileum
- decreases pancreatic secretions
20
What are the five different cell types in the endocrine pancreas and what hormones do they secrete?
What is the role of insulin in carbohydrate metabolism?
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promotes glucose uptake into cells, enhances glycolysis, and stimulates glycogen synthesis
44
What are the key steps in insulin signaling?
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Insulin binds to insulin receptors → phosphorylation of signaling proteins → translocation of GLUT-4 to the plasma membrane → regulation of protein synthesis
45
Expression/Function of GLUT-1
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E: skeletal muscle and fat
F: Glucose uptake by skeletal muscle and fat under basal conditions
46
Expression/Function of GLUT-2
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E: Pancreatic B-cells, liver, intestine, kidney
F: ensures glucose uptake only when glucose levels are high
47
Expression/Function of GLUT-3
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E: Neurons
F: Works with GLUT-1; allowing glucose to cross BBB and enter neurons
48
What is the primary function of GLUT-4?
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Major insulin-responsive glucose transporter
49
Where is GLUT-4 predominantly expressed?
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Striated muscle and adipose tissue
50
What is the primary mediator of insulin-stimulated glucose uptake?
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GLUT-4
51
How does exercise affect insulin receptors?
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Exercise upregulates the number of insulin receptors.
repeated episodes of acute inflammation → fibrosis and damage
- persistent pain, worsened by fatty meals or alcohol
59
Complications of Pancreatitis
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• steatorrhea
• weight loss, deficiencies of fat-soluble vitamins (A, D, E, and K)
• Long term: diabetes and pancreatic cancer
60
What percentage of the US population has diabetes?
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11.6%
61
How many people have prediabetes in the US?
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97.6 million; 38% of US adults
62
What are the increased risks associated with diabetes?
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CVD, kidney failure, and nonalcoholic fatty liver disease
63
What is the goal of screening asymptomatic adults for prediabetes and type 2 diabetes?
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earlier detection, diagnosis, and treatment, with the ultimate aim of improving health outcomes
64
Diagnostic criterion for Diabetes Mellitus based on HbA1c?
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HbA1c ≥ 6.5%
65
Diagnostic criterion for Diabetes Mellitus based on Fasting Plasma Glucose (FPG)?
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FPG ≥ 126 mg/dL
- fasting is defined as no caloric intake for at least 8 hours.
66
What is the definition of Glycated hemoglobin (A1C)?
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Glycated hemoglobin (A1C) is a measure of average blood glucose levels over the past 2-3 months, as around 3% of hemoglobin in circulating red blood cells (RBCs) becomes glycated during their lifespan.
What is the prevalence of Type 2 Diabetes Mellitus?
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Affect around 90% of the diabetic population.
85
What is insulin resistance?
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subnormal cellular response to normal insulin conc. → abnormal glucose metabolism, fatty liver, skin pigmentation, inflammation, and increased risk for conditions like CKD, CVS, and PCOS.
86
How does the pancreas respond to insulin resistance?
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pancreas upregulates insulin production to match the hyperglycemic load
- can lead to amyloid polypeptide buildup and aggregation in the islets
87
What is compensatory hyperinsulinemia?
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body produces excess insulin to counteract the effects of insulin resistance
- prevents clinical appearance of diabetes for many years
88
What happens to beta cell function in diabetic patients over time?
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overburdening of the beta cell mass → decrease in beta cell function over time → deficiency of insulin
89
What are the clinical manifestations of type 2 diabetes?
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nonspecific; fatigue, pruritus, recurrent infections, visual changes, neuropathy-related symptoms, acanthosis nigricans, and polyuria, polydipsia, and weight loss
90
What is acanthosis nigricans?
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brownish pigmentation due to insulin resistance and insulin-mediated IGF-1 activation in keratinocytes
91
What is the management strategy for Type 1 diabetes?
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exogenous insulin to compensate for endogenous insulin deficiency
92
What is the first-line management strategy for Type 2 diabetes?
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First line: diet and exercise to attain a healthy body weight
Combo of anti-hyperglycemic meds
93
What is the blood glucose level that defines hypoglycemia?
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Blood glucose <70 mg/dL
94
What are the symptoms of autonomic system activation associated with hypoglycemia?
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Palpitations, sweating, shaking, nausea, hunger
95
What are the neuroglycopenic symptoms associated with hypoglycemia?
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• focal neurological deficit
• mental confusion
• coma
96
What is Diabetic Ketoacidosis (DKA)?
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T1D; insulin deficiency, increased glucagon levels, and the accumulation of acidic ketone bodies, leading to metabolic acidosis
97
What are the key pathophysiological steps in DKA?
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decreased insulin → glucagon ratio → promoting lipolysis → increased fatty acid production → conversion of fatty acids to ketone bodies → hepatic output of ketone bodies
98
What are the symptoms of DKA (Diabetic Ketoacidosis)?
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Nausea/vomiting, thirst/polyuria, abdominal pain, and shortness of breath (kussmaul breathing).
99
What are the precipitating events for DKA?
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inadequate insulin administration, infection, infarction, pancreatitis, drugs (cocaine), and pregnancy
100
Management of DKA
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• IV fluids to replenish the lost fluids
• administration of insulin & electrolyte monitoring
101
What is the definition of Diabetic Ketoacidosis?
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a life-threatening medical condition caused by severe hyperglycemia in the absence or deficiency of insulin, requiring hospitalization due to ketonemia >1.5 mmol/L, ketonuria, and hyperglycemia
102
What is Ketosis and how does it differ from Diabetic Ketoacidosis?
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an increase in ketone bodies concentration, from keto or low carbohydrate diet/fasting
- Differs: not life-threatening and does not require hospitalization
- partial and complete lack of consciousness
- seizures, coma, death
107
What are the long-term complications of diabetes?
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- microvascular: eye, kidney, and nerves
- macrovascular: brain, heart, and extremities
108
What is neuropathy in the context of diabetes?
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damage to the peripheral nervous system caused by hyperglycemia, leading to pain, numbness, and slow-healing foot wounds
109
What is the effect of hyperglycemia on the risk of infections?
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Hyperglycemia increases the risk for infections due to impaired immune responses and slower wound healing.
110
Hyperglycemia + Infection risks are attributed to
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• hypoxia
• decreased blood supply
• recurrent infections
• impairment of innate and adaptive immune systems
• slower collagen synthesis and decreased angiogenesis
111
What are the key factors contributing to xerostomia and hyposalivation in diabetes mellitus patients?
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• Damage to salivary gland parenchyma
• alterations in salivary gland microcirculation
• dehydration
• mitochondrial dysfunction
112
Diabetes+ xerostomia complications
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caries, damage to the gingiva and supporting tissues, increased risk for infection
113
What is the two-way relationship between diabetes and periodontal disease?
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• Damage to the gingiva and supporting tissues is more extensive
• treating periodontal diseases may improve glycemic control
114
What is Gestational Diabetes Mellitus (GDM)?
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transient form of diabetes that occurs during pregnancy due to increased insulin resistance
115
What is the prevalence of GDM compared to Overt Diabetes?
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GDM is more common (80%) compared to Overt Diabetes (15-20%).
116
What is the pathophysiology of gestational diabetes?
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• exact mechanism is unknown
• insulin resistance, inadequate insulin secretion, and pregnancy hormones are contributing factors
117
What are the complications of gestational diabetes?
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• Hyperglycemia and excessive fetal growth → increase the risk of maternal morbidity
• 3rd trimester pregnancy loss/stillbirth
• fetal complications.
118
What is Diabetes Insipidus?
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excretion of abnormally large volumes of dilute urine without an elevated blood sugar level
119
What are the symptoms of Diabetes Insipidus?
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polyuria (2-20 L/d) and polydipsia
120
What are the two types of Diabetes Insipidus?
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• Central diabetes insipidus: deficient secretion of anti-diuretic hormone (ADH)
• Nephrogenic diabetes insipidus: renal resistance to the anti-diuretic hormone