Nichols + ??? 2 Flashcards
1
Q
Acinar Cell: Protective Mechanisms
A
- Inactive proenzymes
- Membrane enclosed
- Separate pathways
- Trypsin inhibitor
2
Q
Acinar Cell: Acute Pancreatitis, mechanisms of injury
A
- Blockage of Secretion
- Co-localization of ZG and lysosomes
- premature zymogen activation
- autodigestion from within acinar cell
3
Q
Cytokines and Acute Pancreatitis
A
- Proteases activate complement
- C3a and C5a recruit PMNs and macrophages
- Inflammatory cells release cytokines (TNF-alpha, IL-1, PAF, NO)
- Vascular injury and inflammatory responses
4
Q
Local Effets
A
- autodigestion of the pancreas
- pancreatic swelling (edema)
- fat necrosis and hemorrhage
pain, nausea, vomiting
5
Q
Systemic Containment Response
A
- circulation alpha1-antitrypsin (inactivates circulating proteases)
- Circulating alpha-macroglobulin
- binds to circulating trypsin
- facilitates monocyte clearance of macroglobulin-tyrpsin complexes
6
Q
Severe Pancreatitis: Inflammatory
A
Cause: TNF-alpha, IL-6
-fever, malaise, confusion
7
Q
Severe Pancreatitis: Vascular
A
Cause: kallikrein - hypotension
thrombin activation - DIC, hemorrhage
elastase - hemorrhage
chymotrypsin - hemorrhage
8
Q
Severe Pancreatitis: Respiratory
A
Cause: Phospholipase A2 - hypoxemia
9
Q
Severe Pancreatitis: Metabolic
A
Cause: Fat Saponification - hypocalcemia
10
Q
Acute Pancreatitis: Causes
A
gallstones & alcohol
11
Q
Acute Pancreatitis: Symptoms
A
abdominal pain, nausea, vomiting
12
Q
Acute Pancreatitis: Diagnosis
A
- elevated serum amylase and lipase
- inflamed pancreas on CT scan
13
Q
Acute Pancreatitis: Management
A
IV fluids, pain meds, remove stone (if causative)
14
Q
Acute Pancreatitis: Etiologies
A
-miscellaneous
-autoimmune, hyperlipidemia, hypercalcemia, drugs, infection, iatrogenic, trauma, shock, genetic, scorpion bite
40% alcohol
40% gallstones
15
Q
Hereditary Pancreatitis
A
tyrpsinogen mutation (arg to his) where degradation of trypsin cleavage is
16
Q
Acute Pancreatitis: Diagnostic Criteria
A
2 of the 3
- abdominal pain, nausea/vomiting
- elevated serum amylase & lipase more than 3x upper limit of normal
- CT imaging showing pancreatic inflammation
17
Q
Factors suggesting Pancreatitis is from Gallstone
A
- age >50
- female
- amylase > 4000 IU/L
- AST > 100 U/L
- alk. phos. >300 IU/L
18
Q
Acute Pancreatitis: Supportive Management
A
- close observation (hospital)
- NPO
- very aggressive IV fluid replacement
- relief of pain
- nutritional support (if prolonged)
- antibiotics (if biliary pancreatitis)
19
Q
Acute Pancreatitis: Predictors of Poor Outcome
A
- admission hematocrit >44% with failure to decrease after 24hrs of IV fluids
- admission BUN>25mg/dl with an increase after 24 hrs of IV fluids
20
Q
Acute Pancreatitis: Clinical Prognosis CT
A
- Interstitial Pancreatitis (85%)
- multi-organ failure rate < 10%
- infection rate <1%
- mortality ~3%
- Necrotizing Pancreatitis (15%)
- multi-organ failure rate 50%
- infection rate 15-20%
- mortality 17%
21
Q
Complications of Acute Pancreatitis
A
- fluid collections
- pseudocysts
- fistulas (ascites, pleural effusions)
- splenic vein thrombosis
22
Q
Chronic Pancreatitis: Pathophysiology
A
-recurrent injury with tissue destruction and fibrosis
23
Q
Chronic Pancreatitis: Cause
A
chronic alcohol
24
Q
Chronic Pancreatitis: Symptoms
A
chronic abdominal pain
diabetes
steatorrhea
25
Chronic Pancreatitis: Diagnosis
imaging studies
26
Chronic Pancreatitis: Management
pain medications
insulin
enzyme supplements
27
Chronic Pancreatitis: Etiologies
80% alcohol
| miscellaneous: cystic fibrosis, hereditary, tropical, autoimmune
28
Chronic Pancreatitis: Pathophysiology
- chronic alcohol ingestion goes to recurrent bouts of pancreatitis and injury, and abnormal secretion (protein plugs and ductal obstruction - calcification)
- the injury: stellate cell activation, fibrosis, pain & cell death, malabsorption diabetes
29
Chronic Pancreatitis: Pathology
- little dark blue dots (lymphocytes), acini are gone, ducts still present (empty)
- residual necrotic debris
- early fibrosis
30
Chronic Pancreatitis: Clinical Presentation
- chronic abdominal pain ~80%
- malabsorption (steatorrhea) ~35%
- diabetes ~35%
31
Chronic Pancreatitis: Causes of Pain
1. increased pressure
2. biliary strictures
3. acute focal pancreatitis
4. Neural Inflammation
32
Chronic Pancreatitis: Pain Managemetn
narcotics
acute exacerbations - abstinence, enzymes
neural inflammation -nerve block, splanchniectomy
ductal hypertension - drainage (stent/surgery)
pseudocyst pressure - drainage (stent/surgery)
33
Chronic Pancreatitis: Steatorrhea
-fat malabsorption occurs before protein or carbohydrate
-due to lipase deficiency
-treatment: reduce dietary fat intake
oral enzyme supplementation
acid suppression therapy
34
Chronic Pancreatitis: Diabetes
- only seen in severe disease (>80% gland destroyed)
- loss of both insulin and glucagon, difficult to control (brittle)
- low insulin requirements
- ketoacidosis is rare
35
Cystic Fibrosis: Pathophysiology
- genetic disorder of defective chloride secretion
- defective chloride secretion, inspissated secretory product, obstruction of ducts and lumens, infection, inflammation, tissue destruction
36
Cystic Fibrosis: Presentation
pediatric
37
Cystic Fibrosis: Symptoms
lung infection
chronic pancreatitis
hypertonic sweat
38
Cystic Fibrosis: Diagnosis
sweat chloride test
39
Cystic Fibrosis: Treatment
antibiotics
| pancreatic enzymes
40
Cystic Fibrosis
- autosomal recessive
- most common lethal genetic mutation in caucasians (~1:25)
- most CF is caused by a 3 base pair deletion (F508) that affects the folding, processing, and functioning of CF gene product, the cystic fibrosis transmembrane conductance regulator
- CFTR is a cAMP-activated chloride channel
41
Cystic Fibrosis: Clinical Manifestations
- obstructive/ inflammatory lung disease
- chronic pancreatitis
- hypertonic sweat
- hepatobiliary tract disease
- meconium ileus in infants
- infertility
42
Pancreas: Pathology
- minimal pink fibrous tissue
| - minimal thin secretions in ducts
43
Cystic Fibrosis: Pathology
-numerous ducts severely distended with inspissated, dark pink secretions, atrophy of acini and mildly increased fibrous tissue
44
Cystic Fibrosis: Diagnosis
Clinical Symptoms: frequent pulmonary infections (pseudomonas) diarrhea, malabsorption, failure to thrive, frequent episodes of dehydration
Testing: sweat chloride test, pulmonary function tests, genetic testing
45
Cystic Fibrosis: Clinical Management
- daily pulmonary toilet/inhalers
- treatment of pulmonary infections
- high dose pancreatic enzymes
- gene transfer?
46
Cystic Diseases of Pancreas
- pancreatic cysts can be either benign or malignant
- most common benign cyst-like lesion in pancreas is pseudocyst
- serous ones have very little malignant potential whereas mucinous ones have malignant potential
47
Benign Pancreatic Cysts
- pseudocysts - very common (chronic pancreatitis)
| - rare non-neoplastic cysts
48
Cystic Neoplasms
- serous cystic tumors (benign)
- mucinous cyst neoplasms
- intraductal papillary mucinous neoplasms
- solid pseudopapillary neoplasms
49
Cystic Diseases: Diagnostic Evaluation
- imaging to assess cyst size
- endoscopic ultrasound (structure, obtain fluid and tissue for analysis)
- serum tumor markers (CEA for mucinous cystic neoplasm)
- ERCP for intraductal papillary mucinous neoplasms
50
Pancreatic Cancer
- vast majority are adenocarcinomas of ductal origin
- abdominal pain & weight loss
- prognosis is poor unless caught VERY early
51
Pancreatic Cancer Histology
90% are ducal adenocarcinomas
10% miscellaneous (cystic neoplasms, acinar cell neoplasms, lymphomas & sarcomas, neuroendocrine tumors) gastrinoma, insulinoma, glucagonoma
52
Risk factors for pancreatic Cancer
- cigarette smoking
- alcohol in setting of chronic pancreatitis
- hereditary pancreatitis
- family history of pancreatic cancer
53
Diagnosis of Pancreatic Adenocarcinoma
Features: weight loss, abdominal pain, jaundice
Lab Tests: elevated serum CA19-9 (tumor marker)
Imaging: mass of CT or MRI,endoscopic ultrasound with FNA
54
Management Considerations of Pancreatic Cancer
-70% arise in the head of pancreas
-presentation: 40% metastatic (unresectable)
40% advanced local disease (unresctable)
20% organ confined (resectable), less than 1/2 can be cured
-Chemo & radiation therapy have limited effectiveness
55
Surgery for Pancreatic Cancer
```
Cure: for tail lesions (distal pancreatectomy)
-for head (Whipple resection)
Palliation: relieve biliary obstruction
-relieve gastric outlet obstruction
-splanchnietomy for pain control
```
56
Tumors of Small and Large Intestine
- small intestine: rare
- colon & rectum: more primary than any other organ
- colon cancer mortality: 2nd only to lung cancer
- 5% americans get CRC, 40% will die
- 70% of colorectal tumors are adenocarcinomas
57
Polyp
bump or nodule in the mucosa
1. sessile
2. pedunculated
3. papilloma
58
Non-neoplastic Polyps: Hyperplastic
sawtooth (serrated) lumens, due to overgrowth of mature cells in crypt bases, from KRAS mutation without APC mutation
59
Non-neoplastic Polyps: Hamartoma
mass of mature, but disorganized tissue indigenous to site (Peutz-Jaghers syndrome)
60
Non-neoplastic Polyps: Juvenile
retention in adults
| -chronic inflammation, ulceration, dilated glands
61
Adenomatous Colon Polyps
most common type
- glandular structure can be tubular, villous, or tubulo-villous
- has malignant potential
62
Hyperplastic Colon Polyps
- diminutive, dilated glands
| - no malignant potential
63
Inflammatory Colon Polyps
- occur in long-standing IBD
| - not neoplastic
64
Epidemiology of Colorectal Cancer
- most common GI malignancy
- Higher incidence in developed countries
- thought to be secondary to high fat, low fiber diet
- Ca and folate in diet may be protective
- Folate may have anti-cancer benefit early in adenoma sequence
65
Increased Risk of Colorectal Cancer
-lack of physical activity
-red meat
-obesity
-cigarette smoking
-alcohol use
(diet & geography, age, family history, chronic colitis, adenoma, previous colorectal neoplasia)
66
Decreased Risk of Colorectal Cancer
- multivitamin containing folic acid
- aspirin & other NSAIDS
- postmenopausal hormone use
- Ca supplementation
- Selenium
- Consumption of Vegetables, Fruits, and Fiber
67
Presentation: Impact of Location
Ascending: Occult bleeding, anemia
Descending: Obstructive symptoms, overt bleeding
Rectum: Tenesmus, Pain, Bleeding
68
Barium Enema in Diagnosis of CRC
show mass or constricting lesion
69
Colon Cancer and Colonoscopy
- locate lesion
- remove polyps
- biopsy of lesions
70
Treatment of Colon Cancer
- endoscopic polypectomy can be curative if cancer is localized to head of polyp
- pre-op CT to look for metastatic disease
- surgery is mainstay of treatment, involves removal of tumor and adjacent lymphatic
71
Prognosis of Colon Cancer
```
-worsens as extent of invasion increases
Mucosa
Submucosa
Muscularis
Serosa
Lymph nodes
Dukes
```
72
Chemo in CRC
1. Adjuvant Treatment in patients with positive nodes
| 2. Decreases recurrences and improves survival
73
Colon Polyp Progression to CRC
1. APC
2. KRAS/BRAF
3. p53, PIK3CA, loss of 18q
4. P53
74
Endoscopic Polyectomy
-removal of a stalked polyp with colonoscopy using cautery and a snare
75
Tumor Suppressor Genes
- genes that function normally in inhibition of cell growth
| - abnormalities in tumor suppressor genes may be inherited
76
Oncogenes
- activation results in uncontrolled cellular proliferation
- activation is usually from environmental stimuli
- oncogenes are generally not inherited
77
Colonic neoplasia
(polyps and cancer) results from the accumulation of mutations (inherited and/or sporadic) of cellular oncogenes, tumor suppressor genes, and DNA repair genes that cause dysregulation of normal cellular growth
78
Familial Adenomatous Polyposis (FAP)
-autosomal dominant
>100 adenomatous polyps starting in (2nd & 3rd decade)
-all develop CRC without colectomy
-may also have gastric fundic gland polyps, duodenal adenomas and cancer, periampullary adenomas and cancer, desmoid tumors, and retinal pigmented lesions
79
Genetic Etiology of FAP
- one allele of the APC gene inherited in a mutated form (germ line mutation)
- this mutation present in every cell of the colon
- polyp growth begins when the second allele is somatically mutated thus causing loss of gene function
80
Hereditary Non-Polyposis CRC (HNPCC)
- germline mutation
- accounts for 5% of CRC in US
- proximal colon lesions are common
- may also be associated with endometrial, ovarian, urinary, and gastric cancer
- more common than FAP
81
Diagnosis of HNPCC
1) one relative with CRC at age <50
2) CRC spans 2 generations
3) 3 relatives with HNPCC tumors - 2 must be first degree relatives of 3rd
82
Goals of Screening for CRC
1) decrease mortality from colon cancer
| 2) prevent colon cancer by removing adenomatous polyps
83
Colorectal Cancer Screening
- average risk: asymptmatic, age >50, US Task Force recommended to stpo screening at age 75
- High Risk: asymptomatic, personal history of adenomas or cancer, family history, hereditary cancer (FAP, HNPCC), IBD colitis
84
Fecal Occult Blod in the Diagnosis of CRC
Phenolilc Guaiac (colorless) - peroxidase - Pigmented Quinone (turns in blue)
85
Fecal Immunochemical Test (FIT)
- responds to only human hemoglobin
- does not detect UGI bleeding
- requires 1 or 2 stool samples
- may detect as little as 0.3gmHb/gm stool
- more expensive than Guiac
- more sensitive & specific than Guiac
86
Virtual Colonoscopy
- helical CT reconstructed into 3D images
- studies on sensitivity & specificity have been variable
- requires bowel prep
- exposure to radiation
- not widely available
- role in screening is unclear
- positive test requires colonoscopy
87
Barriers to Colon Screening
1. Limited access to medical care or colonoscopy
2. Patient preference-bowel prep, time off from work for colonoscopy
3. Risk and expense of screening test
- best test for individual patient is test that gets done
- only 65% of patients currently get screening between 50-75
88
Colon Neoplasms: Benign Polyps
Adenomas: 2 Types
1. Tubular: more pedunculated
2. Villous: larger, more sessile, higher risk of malignancy
89
Colon Neoplasms: Malignant Neoplasms
Adenocarcinoma: 2 Forms
1. Polypoid
2. Annular
90
Malignant Small Bowel Tumors
-2% of all GI tract cancers
<0.4% of all cancers
-mean age diagnosis-65Y
-adenocarcinoma and carcinoid most common
91
Signs & Symptoms of Small Bowel Tumors
- vague, non-specific-delay in diagnosis of 8-12 months
- crampy abdominal pain
- weight loss
- nausea/vomiting
- GI bleeding/anemia
- Jaundice with ampullary lesions
- symptoms more likely with malignant lesions
