Nichols + ??? 2 Flashcards Preview

GI > Nichols + ??? 2 > Flashcards

Flashcards in Nichols + ??? 2 Deck (91)
1

Acinar Cell: Protective Mechanisms

1. Inactive proenzymes
2. Membrane enclosed
3. Separate pathways
4. Trypsin inhibitor

2

Acinar Cell: Acute Pancreatitis, mechanisms of injury

1. Blockage of Secretion
2. Co-localization of ZG and lysosomes
-premature zymogen activation
-autodigestion from within acinar cell

3

Cytokines and Acute Pancreatitis

-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

Local Effets

-autodigestion of the pancreas
-pancreatic swelling (edema)
-fat necrosis and hemorrhage

***pain, nausea, vomiting***

5

Systemic Containment Response

-circulation alpha1-antitrypsin (inactivates circulating proteases)
-Circulating alpha-macroglobulin
-binds to circulating trypsin
-facilitates monocyte clearance of macroglobulin-tyrpsin complexes

6

Severe Pancreatitis: Inflammatory

Cause: TNF-alpha, IL-6
-fever, malaise, confusion

7

Severe Pancreatitis: Vascular

Cause: kallikrein - hypotension
thrombin activation - DIC, hemorrhage
elastase - hemorrhage
chymotrypsin - hemorrhage

8

Severe Pancreatitis: Respiratory

Cause: Phospholipase A2 - hypoxemia

9

Severe Pancreatitis: Metabolic

Cause: Fat Saponification - hypocalcemia

10

Acute Pancreatitis: Causes

gallstones & alcohol

11

Acute Pancreatitis: Symptoms

abdominal pain, nausea, vomiting

12

Acute Pancreatitis: Diagnosis

-elevated serum amylase and lipase
-inflamed pancreas on CT scan

13

Acute Pancreatitis: Management

IV fluids, pain meds, remove stone (if causative)

14

Acute Pancreatitis: Etiologies

-miscellaneous
-autoimmune, hyperlipidemia, hypercalcemia, drugs, infection, iatrogenic, trauma, shock, genetic, scorpion bite
40% alcohol
40% gallstones

15

Hereditary Pancreatitis

tyrpsinogen mutation (arg to his) where degradation of trypsin cleavage is

16

Acute Pancreatitis: Diagnostic Criteria

2 of the 3

1. abdominal pain, nausea/vomiting
2. elevated serum amylase & lipase more than 3x upper limit of normal
3. CT imaging showing pancreatic inflammation

17

Factors suggesting Pancreatitis is from Gallstone

1. age >50
2. female
3. amylase > 4000 IU/L
4. AST > 100 U/L
5. alk. phos. >300 IU/L

18

Acute Pancreatitis: Supportive Management

-close observation (hospital)
-NPO
-very aggressive IV fluid replacement
-relief of pain
-nutritional support (if prolonged)
-antibiotics (if biliary pancreatitis)

19

Acute Pancreatitis: Predictors of Poor Outcome

-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

Acute Pancreatitis: Clinical Prognosis CT

1. Interstitial Pancreatitis (85%)
-multi-organ failure rate < 10%
-infection rate <1%
-mortality ~3%
2. Necrotizing Pancreatitis (15%)
-multi-organ failure rate 50%
-infection rate 15-20%
-mortality 17%

21

Complications of Acute Pancreatitis

-fluid collections
-pseudocysts
-fistulas (ascites, pleural effusions)
-splenic vein thrombosis

22

Chronic Pancreatitis: Pathophysiology

-recurrent injury with tissue destruction and fibrosis

23

Chronic Pancreatitis: Cause

chronic alcohol

24

Chronic Pancreatitis: Symptoms

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