Exam 1 Flashcards
(335 cards)
1
Q
Submucosal plexus
A
Nerve plexus in GI tract, below mucosa
Regulates secretion
2
Q
Myenteric plexus
A
Nerve plexus in GI tract between circular and longitudinal muscle
Regulate motility and smooth muscle contraction
3
Q
Input to enteric plexi
A
From spinal cord - sympathetic and parasympathetic autonomics
Enteric inputs - proprio and chemoreceptors within mucosa/submucosa
4
Q
Outputs from enteric plexi
A
Regulate function of GI tract
Secretion, motility
5
Q
Sympathetic innervation of GI tract
A
Directly innervate pancreas, liver, gall bladder, vascular smooth muscle of feed arterioles
General inhibition, vasoconstriction
6
Q
Parasympathetic innervation of salivary glands
A
7th and 9th cranial nerves
Increase motor/secretory function
7
Q
Parasympathetic innervation of GI (not salivary)
A
Vagus
Secretion and motility
8
Q
Gastrin: Stimulus, action
A
Stimulated by peptides, amino acids, stomach distention
Function: Stimulate acid secretion and GI growth
9
Q
Secretin: Stimulus and action
A
Stimulus: Duodenal acidity
Action: Pancreatic bicarb secretion
10
Q
CCK stimulus and action
A
Stimulus: Fatty acids, amino acids in intestine
Action: Gall bladder contraction, pancreatic enzyme secretion and growth
11
Q
GIP: Stimulus and action
A
Stimulus: Glucose, fatty acids in intestine
Action: Insulin release
12
Q
High levels of CCK stimulate…
A
Activates motility of stomach and closure of pyloric sphincter
13
Q
Incretins
A
GIP
GLP
Insulin secretion, reduced glucagon secretion
GLP-1 inhibits gastric emptying
14
Q
Gastrin and CCK family overall
A
Increase intracellular Ca in target cells
15
Q
Secretin hormone family: Members and physiological function
A
VIP, GIP, GLP-1
Increase cAMP and AC activity
16
Q
Hormone concentration and length of intestine relationship
A
Increased length along GI tract = more hormone
17
Q
CCK primary location
A
Intestine
18
Q
Gastrin primary location
A
Stomach antrum
19
Q
Secretin cell primary location
A
Intestine
20
Q
GIP secreting cell primary location
A
Intestine
21
Q
GLP-1 secreting cell primary location
A
Small intestine and colon
22
Q
Pancreatic polypeptide stimulus and action
A
Stimulus: glucose
Action: decrease pancreatic bicarb and enzyme secretion
23
Q
Ghrelin
A
Stimulates appetite
Decrease insulin release
24
Q
Motilin
A
Initiates or sensitizes gastric motility
Initiates or sensitizes intestinal motility
25
Entero-oxyntin
Stimulate acid secretion
26
Enterogastrone
Inhibit acid secretion
27
Non adrenergic, non cholinergic neurotransmitters
GI modulating peptides released from nerve endings in neural plexi
28
NANC: VIP and Guanylin
Nerve ending location and action
Location: Mucosa and muscle of gut, colon
Action: SM relaxation, increase cAMP, activate NaCl and water secretion
29
NANC: GRPor bombesin
Location and action
Location: gastric mucosa
Action: gastrin release
30
NANC: Enkephalins
Location and action
Location: Mucosa and muscle of gut
Action: Sphincter muscle contraction
31
NANC: Supbstance P
Location and action
Location: salivary glands
Action: Secretion, enhance blood flow
32
NANC: CCK
Location and Action
Location: Enteric and hypothalamic neurons
Action: Inhibit propulsion, activate satiety
33
Somatostatin
Paracrine
Stimulated by low pH (\<2-3) in pylorus
Decrease gastrin secretion
34
Histamine
Paracrine
Stimulate acid secretion
Activate crypt fluid secretion in intestine and colon
35
Salivary glands in mouth
Parotid - fluid
Sublingual - mucous
Submandibular - mixed
36
Salivary composition
Water
Ions
Organic compounds
37
Organic compounds in saliva
a amylase - starch digestion (pH 7.0)
lingual lipase - fat digestion (pH 4.0)
Lysozyme - anti bacterial
38
Protective effects of saliva
I-, SCN-
IgA
Lysozyme
Lactoferrin
39
Sympathetic stimulation of salivary glands
cAMP increase
Release of proteins (digestive enzymes)
Vasoconstriction so no water/fluid flow
40
Parasympathetic stimulation of salivary glands
Ca increase
HCO3 and protein secretion
Vasodilation - increased fluid flow
41
AcH effects on saliva
HCO3 and protein secretion
42
Substance P effect on salivary glands
Vasodilation and increased fluid flow
43
Cardiac glands
Proximal stomach
Secrete mucus
44
Gastric (oxyntic glands)
Central 3/4 of stomach
Secrete HCl, Pepsinogen, Intrinsic factor
45
Pyloric glands
Secrete mucus into stomach and gastrin into blood
46
Cells of gastric glands
Chief cells - Pepsinogen
Mucus secreting cells - Mucopolysaccharides
Parietal cell - HCL, IF
47
Mechanism of parietal cell HCl secretion
H/K ATPase
H20 + CO2 -- CA --\> H2CO3 --\> H + HCO3
HCO3 pumped out of basolateral side through HCO3/Cl antiporter
48
Mechanisms of regulation for acid secretion
Parasympathetic --\> Ach --\> Increase Ca --\> HCl secretion
Digested peptides/stomach distention/GRP --\> Gastrin --\> Increase Ca --\> HCl secretion
Histamine --\> H2 receptor --\> cAMP --\> Potentiate HCL secretion
Histamine constitutively active
49
Cephalic phase of acid secretion
Chewing, swallowing stimulus
Vagus nerve --\> Parietal cell + G cell activation
50
Gastric phase of acid secretion
Stimulus - Gastric distention
Local and vagovagal reflexes --\> Parietal, G cell
51
Intestinal phase of acid secretion
Protein digestion products in duodenum
Activate intestinal endocrine cells
52
Enterochromaffin cells
Secrete Histamine
Constitutively active cells, basal level
53
G cell and S cell
G cell: Vagus activation + protein digestion activation --\> secrete Gastrin
S cell: Vagus activation + low pH activation --\> Inhibit G cell
54
Aphthous ULcers
Inflammatory lesions
Association with Crohns/UC
55
Forms of candidiasis
Psudomembranous candidiasis (Thrush)
Erythematous candidiasis
Hyperplastic candidiasis
56
Thrush
Pseudomembranous candidiasis
Superficial, gray to white inflammatory membrane
Underlying erythematous inflammatory base layer
Worsoned infection in immunosuppressed patients, if on antibiotics that destoy normal oral flora
57
Erythematous candidiasis
Red, raw looking lesion
May evolve from pseudomembranous candidiasis
Associated with inhaled steroids
Appears on dorsum of tongue, loss of lingual papillae
58
Hyperplastic candidiasis
Nodular, plaque like
White persistent plaque, does not wipe off
59
Treatment of oral candidiasis
Nystatin - topical use
Fluconazole - Inhibit P450 and reduces sterol synthesis
Caspofungin - Echinocandin, decrease cell wall synthesis
60
Leukoplakia
Oral, white patch that cannot be scraped off
Not characterized as any other disease
5-25% can progress to SCC
Tobacco = risk factor
61
Erythroplakia
Less common than leukoplakia, more serious
Red, velvety lesion
Atypical dysplastic lesion, highly prone to progress to SCC
62
Oral hairy leukoplakia
Lateral portion of tongue
Associated with immune compromised patients
Caused by EBV
63
Traditional SCC
Smokers, 60s, oral lesion that infiltrates locally before mets
64
HPV associated SCC
Expression of HPV E6 and E7 protein --\> inactivate p53 and RB --\> tumor growth
65
Sjogrens disease: Definition and symptoms
Autoimmune disease that destroys exocrine glands
Associated with RA
Joint pain, xerostomia, dry eyes
66
Sjogrens pathogenesis
Glandular cells present antigen to T cells --\> cytokine activation (IF-gamma, IL2)
B cell activation
67
Pleiomorphic adenoma
Benign mixed tumor
Most common tumor of Parotid gland
Treat with surgical incision
68
Warthin tumor
Papillary cystoadenoma lyphomatosum
Benign cystic tumor
Parotid gland
69
Mucoepidermoid carcinoma
Most common malignancy of minor salivary glands
Increased risk with radiation exposure
Mucous and squamous cell portions
70
GERD definition and pathogenesis
Reflux of stomach acid into esophagus
Decreased anti reflux, hiatal hernia, decreased gastric emptying
71
Clinical features of GERD
Dysphagia, heart burn, chest pain, hematemesis
72
Microscopic findings of GERD
Epithelial basal zone hyperplasia
Eosiniphils, lymphocytes, neutrophils
73
GERD complications
Bleeding
Strictures
Barrets
74
Barrets Esophagus
Long standing GERD
Squamous cells --\> columnar
Presence of goblet cells increases cancer risk
Adenocarcinoma
75
Eosinophilic Esophagitis
Food allergy main cause
Eosinophils in esophagus
Rings and furrows --\> can lead to stricture
76
Eosinophilic esophagitis treatment
PPI - reduce eosinophil recruitment
Steroids
77
Infectious esophagitis most common etiology
HSV
CMV
78
Cell types affected in HSV and CMV esophagitis
HSV - epithelial cells
CMV - stromal cells
79
Inclusions in HSV and CMV
HSV - nuclear inclusion in multinucleated cells
CMV - nuclear and cytoplasmic inclusions in single cells
CMV has englarged cels (cytomegaly)
80
Location of viral cells relative to ulcer, HSV/CMV
HSV - Edge of ulcer
CMV - base of ulcer
81
Portosystemic anastamoses
1. Umbilical
2. Esophageal
3. Retroperitoneal
4. Superior anal canal
82
Esophageal SCC
More common in underdeveloped countries
No connection to BE
Squamous dysplasia due to smoking/alcohol
Middle 1/3 esohagus
83
Esophageal adenocarcinoma
More common in developed countries - obesity
Related to BE
Lower 1/3 esophagus/GE j(x)
84
H Pylori gastritis: Definition and types
Inflammation of stomach due to H Pylori infection
Most common cause of chronic gastritis
1. Antrum
2. Pan gastritis
85
Antral gastritis
Increased acid secretion --\> duodenal ulcers
86
Pangastritis
Multifocal atrophc gastritis
Decreased parietal cells --\> decreased acid --\> intestinal metaplasia --\> carcinoma
87
Sequelae of H pylori gastritis
1. Peptic ulcer disease
2. Gastric adenocarcinoma, intestinal type
3. MALToma
88
Autoimmune gastritis: Definition and pathogenesis
Autoimmune disease targeting H/KATPase of Parietal cell (CD4 T cells)
Chief cell damaged because of inflamamtion
89
Characterstics of of autoimmune gastritis
1. Decreased parietal --\> decreased acid --\> disinhibition of gastrin cells --\> ECL proliferation --\> carcinoid tumor
2. Decreased IF --\> B12 deficiency --\> megaloblastic anemia
3. Decreased acid --\> decreased iron absorption
4. Intestinal metaplasia --\> Dysplasia --\> Adenocarcinoma
90
Peptic ulcer disease causes
1. H Pylori
2. NSAIDs
3. Smoking
91
Benign peptic ulcer characteristics
Sharp, punched out
Clean base b/c acid digesting necrotic debris
Normal rugae surroundings
Acid digestion can go deep and cause severe bleed
92
Malignant peptic ulcer characteristics
Irregular shape
Base contains necrotic debris
Damage to surrounding rugae
93
Peptic ulcer disease characteristics
1. Bleeding
2. Perforation
3. Gastric outlet obstruction
94
Hypertrophic gastropathy types
1. Menetrier Disease
2. Zollinger Ellison
3. Hypertrophic hypersecreting
95
Menetrier Disease
Increased TGF-B secretion
Diffuse hyperplasia of foveolar epithelium of body/fundus
Hypersecretion of mucus --\> protein loss in mucus --\> peripheral edema
Hypoplasia of parietal and chief cells
Increased risk of adenocarcinoma
96
Zollinger Ellison syndrome
Gastrin secreting tumor --\> Hyperplasia of parietal cells/ECL cells --\> gastric carcinoid tumor
Duodenal ulcers and chronic diarrhea
97
Hypertrophic hypersecretory gastriopathy
Parietal cell hyperplasia with hypogastrinemia
98
Gastric adenocarcinoma - Intestinal type
Gland forming tumor
Arise from intestinal metaplasia/dysplasia
WNT-B-catenin pathway
Increased incidence in FAP
99
Gastric adenocarcinoma - diffuse type
Rare gland formation
\>50% signet ring cells
Diffuse b/c mutation in CHD1 --\> loss of E cadherin --\> cells fall apart
Can metastasize to ovaries --\> Krukenberg tumor
100
Gastric Carcinoid Tumors
Autoimmune gastritis
Zollinger ellison syndrome
Endocrine cell hyperplasia
101
H Pylori triple therapy
PPI
2 antibiotics
102
Omeprazole
Proton pump inhibitor
Activated in acidic environment
Long acting
103
H2 antagonists
Specific therapy for acid related diseases, ie GERD
Cimetidine, Ranitidine, Famotidine
Decrease acid and pepsin secretion
104
Cimetidine
1st H2 antagonist
Short duration of action
Inhibits P450
105
Ranitidine, Famotidine, Nizatidine
H2 antagonists
Treat GERD and peptic ulcer disease
Longer duration, no anti androgenic effects
106
Types of antacids
NaHCO3
Ca-OH/HCO3
Mg-OH/HCO3
Al-OH/HCO3
107
Sodium Bicarb antacid: onset, duration, alkalosis, stool effect
Rapid onset
Short duration
Yes alkalosis
No stool effect
108
Mg antacid: onset, duration, alkalosis, stool effect
Rapid onset
Long duration
No alkalosis
Laxative
109
Ca antacid: onset, duration, alkalosis, stool effect
Intermediate onset
Long duration
No alkalosis
Constipating
110
Al antacid: onset, duration, alkalosis, stool effect
Slow onset
Long duration
No alkalosis
Constipating
111
Sucralfate
1. Complexes with proteins at ulcer site --\> protective layer
2. Decreases back diffusion of H ion
3. Binds to pepsin and bile salts
112
Primary GI site of viral disease
Terminal ileum
113
E coli enterocolitis
Water, food, meat source
Shigatoxin producing E Coli --\> Hemolytic uremic syndrome
114
Intestinal TB
Cecal disease most common
Necrotizing granluomatous inflammation
Stricture formation is common
115
Crohns disease: Location and characteristics
Primarily small intestine (terminal ileum)
Skip lesions, transmural inflammation, granulomas (60% cases)
116
Ulcerative Colitis
Mucosal disease, mainly in colon
Predisposed to pre malignancy, higher incidence in UC
117
Celiac Sprue
Cell mediated immune reaction to gluten
Atrophic villi in SI via T cell mediated epithelial destruction
Flat epithelia, diffuse enteritis, inflammatory infiltrate
118
Tropical sprue
Post infectious sprue
Bacterial overgrowth (E Coli, hemophilus)
Epithelium and submucosa equalliy inflamed
119
Psuedomembranous COlitis
C. Diff overgrowth
Shallow superficial ulcers, covered by fibrin, polys, bacteria
All oral antibiotics except Vanco cause it
120
Acute vs chronic ischemic colitis
Acute:
* Mesenteric artery thrombosis
* Intestinal obstruction
* Causes intestinal infarction and peritonitis
Chronic:
* Arteriosclerotic disease, bloody stool and pseudomembranes
121
Irritable Bowel Syndrome
Intermittent abdominal pain and diarrhea
Stress precipitates symptoms
No anatomic change
NM dysfunction/immune disorders may cause it
Symptomatic treatment
122
Shigella COlitis
G- bacteria, developing world
Distal colon
Superficial inflammation
123
Amebiasis of colon
12% of world infected
10% symptomatic, 80% only intestinal disease
Cecum and sigmoid are resevoirs
Entameba histolytica cysts = infectious
Trophozite = destructive
124
Most common infectious agent associated with vomiting (not food poisoning)
Norovirus
125
Most common pathogen causing watery diarrhea
Rotavirus
126
Pathogen/etiologies of malabsorption
Low volume diarrhea, but prolonged
Giardiasis
Lactose intolerance
Celiac
127
Dysentery: Description and patholgical agents
Inflammatory disease of colon
Fever, low abdominal pain, bloody diarrhea
Shigella, Amebiasis, E coli, C diff
128
Syndrome of food poisoning and pathagent/food
Vomiting - S Aureua, Bacillus cerues enterotoxins
Paralysis - Botulinum
Scombroid fish poisoning - heavily muscled fish
Paresthesias - fish, shellfish
Diarrhea - C Perfingens toxin in intestines
129
Cholera MoA
Cholera toxin upregulates cAMP --\> Cl secretion --\> significant water loss
130
Secondary peritonitis
Rupture/perforation of GI tract --\> fecal matter and bacteria spills into peritoneum --\> systemic sepsis --\> so not chill
131
Primary peritonitis (SBP)
Spontaneous bacterial peritonitis
Ascites in peritoneum often due to chronic liver failure, immune defenses low
Bacteria arrive via blood stream or translocation through intestinal wall
Common cause: E Coli, Strep Pneumoniae
132
CAPD and peritonitis
Complication of Continuous Ambulatory Peritoneal Dialysis
Infection occuring due to exposure of peritoneum during PD
133
Clinical presentation of liver disease patients
Systemic symptoms - fever, malaise, nausea, vomiting
Jaundice
Coagulopathy - inadequate production of coagulation factors
Ascites
Portal HTN
134
Location and ratio of aminotransferases
Liver: ALT \> AST
Muscle: AST \> ALT
135
Aminotransferases and liver disease
Damage to hepatocytes (or myocytes) increases enzymes in blood (testable)
Acute hepatitis - Markedly increased ALT/AST
Alcholic liver disease: Increased AST/ALT
136
Alkaline phosphatase and liver disease
Liver injury --\> AP moved to plasma membrane --\> released into blood
Elevations = bile duct injury or infiltrative liver disease
137
Hepatitis A: Virus type, mode of transmission, illness progression
RNA virus transmitted fecal-oral
Age 2-6 usually asymptomatic
Symptomatic infection 4 weeks after exposure: Fever, nausea, malaise, diarrhea --\> jaundice
No chronic infection
Vaccine available
138
Hepatitis B: Virus type, mode of transmission, disease progression
DNA virus transmitted vertically, body secretions, blood
IV drug users, sexual - western world
Vertically - Developing world
Can be asymptomatic, cirrhosis, liver failure
Chronic infection risk decreases with age (90% newborns, 5% adults)
Vaccine available
139
Hepatitis C: Virus type, mode of transmission, disease progression
RNA virus transmitted through blood, IV sharing, transfusions
Acute infection - asymptomatic
Chronic infection 20-60%
Chronic Hep C most common cause of cirrhosis and liver cancer in Western world
No effective vaccine
140
Hepatitis D: Virus type, mode of transmission, disease progression
Defective RNA virus, can only infect people with Hep B
Can acquire B and D at same time
Can acquire D with chronic B --\> liver disease more active
141
Hepatitis E: Virus type, transmission, progression
RNA virus, fecal oral
Developing world
SImilar to Hep A, milder
Pregnant women --\> hepatic failure
142
Hep A serologic testing
IgM - acute infection
IgG - Resolved infection or imunized
143
Hep B serology:
HBsAg negative
anti-HBc negative
anti-HBs negative
Susceptible
144
Hep B serology:
HBsAg negative
anti-HBc positive
anti-HBs positive
Immune due to natural infection
145
Hep B serology:
HBsAg negative
anti-HBc negative
anti-HBs positive
Immune due to HepB vaccine
Vaccine only contains HBs antigen
146
Hep B serology:
HBsAg positive
anti-HBc positive
IgM anti-HBc positive
anti-HBs negative
Acutely infected
147
Hep B serology:
HBsAg positive
anti-HBc positive
IgM anti-HBc negative
anti-HBs negative
Chronically infected
148
Hepatitis C serology
HCV AB+ = carriers, past infection
HCV RNA+ = Chronic carriers
149
Hepatitis D serology
HDV IgM + = positive acute
HDV IgG + = Positive chronic OR past infection
HDV RNA + = chronic
150
Hepatitis A-E treatment
HAV - supportive care, no effective anti virals
HBV - Interferon alpha, nucleoside analog
HCV - Protease inhibtor
HDV - Interferon alpha
HEV - Supportive care
151
Other causes of acute hepatitis
Acetaminophen
Autoimmune hepatitis
Shock
HF
152
Other causes of chronic hepatitis
Autoimmune/sclerosing cholangitis/primary biliary cirrhosis
Alcoholic liver disease
Alpha methyldopa
153
Bacterial infections of liver primary cause
Biliary tract disease (stones causing cholangitis)
Pyogenic abscesses
154
Characteristics of biliary tract disease
Jaundice
Fever
Colic pain
Liver tests - ALP elevated
155
Treatment of biliary tract disease
Drainage of infected bile surgically of ERCP
156
Pyogenic liver abscess characteristics and diagnosis
Chronic fever
CT/MRI, aspiration and culture of abscess material
Treat with antibiotics
157
Bilirubin fractionation = mixed --\> ALP elevation = ?
Cholestatic disease
Biliary tract disease
Look for stones, abscess, tumors in biliary system
158
Bilirubin fractionation = mixed --\> AST/ALT elevation = ?
Hepatitis
Serological testing
159
Bilirubin fractionation = most unconjugated, low elevation = ?
Hemolysis or Gilberts
Physiological jaundice or Crigler Najjar
160
Replicative HBV serology
HBV DNA = High
HBeAG = +
Increased ALT
161
Non replicative HBV serology
HBV DNA low
HBeAg - HBeAb +/-
ALT normal
162
Agenisis of pancreas
Rare condition, complete absence of pancreas
PDX1 gene
163
Pancreas Divisum
Most common congenital abnormality of pancreas
Failure of fusion of fetal pancreatic duct system
Predisposition to chronic pancreatitis
164
Annular pancreatitis
Portion of pancreas wraps around duodenum --\> obstruction
165
Ectopic pancreas
Normal pancreatic tissue present where it shouldn't be
Jejunum, Meckel diverticulum, ileum
166
Acute pancreatitis definition
Reversible pancreatic parenchymal injury, associated with inflammation
167
Common causes of acute pancreatitis
Biliary tract disease
Medication
Infection (mumps)
Alcohol
Ischemic injury (shock, vasculitis, atheroembolism)
168
Pathogenesis of acute pancreatitis
1. Duct obstruction
2. Primary acinar injury
3. Defective intracellular transport of proenzymes
169
Acute panreatitis: Duct obstruction
Blockage of ductal system --\> retrograde intraductal pressure --\> Leakage of enzymes into pancreatic tissues --\> DESTRUCTION --\> cytokine infiltration and inflammation
Inflammation and edema = compromised blood flow --\> more damage
170
Acute pancreatitis: Primary acinar injury
Secondary to alcohol, viruses, drugs, trauma, shock
171
Acute pancreatitis: Defective enzyme transport
Enzymes transported to where they shouldnt be --\> acinar cell damage
172
Alcohol and pancreatitis mechanisms
Increase sphincter of oddi contraction --\> stone obstruction
Toxic effect on acinar cells
Oxidative stress --\> fusion of lysosome and zymogen granules --\> damage to acinar cells
173
Hereditary pancreatitis
10-20% unknown etiology
Recurrent attacks of severe pancreatitis in childhood
Mutations in cationic trypsinogen gene
174
Histology of acute pancreatitis
Microvascular leaks --\> edema
Fat necrosis via lipolytic enzymes
Destruction of parenchyma
Destruction of blood vessels
175
Clinical presentation of acute pancreatitis
Abdominal pain
Epigastric tenderness
Nausea/vomiting
Fever
Hypotension
Subcutaneous fat necrosis
176
Lab evaluation of acute pancreatitis
Elevated serum/urine amylase
Elevated lipase
Hypocalcemia
177
Chronic pancreatitis definition
Inflammation of pancreas with irreversible destruction of exocrine pancreatic parenchyma, fibrosis ---\> endocrine parenchyma destruction
178
Causes of chronic pancreatitis
Most common: Chronic alcohol abuse
Cystic fibrosis (duct plugging)
Drugs, virus, shock, etc
179
Acute pancreatitis treatment
Rest
IV fluids
Pain meds
180
Pancreatic congenital cysts
Anomalous development of pancreatic duct
Lined by uniform cuboidal epithelium
Sporadic
Syndromic - ADPKD, von Hippel Lindau
181
Pancreatic pseudocyst
Localized collection of necrotic/hemorrhagic material rich in pancreatic enzymes
No epithelial lining
Large
Alcohol, traums
182
Serous cystadenoma
Benign cystic neoplasm, clear fluid
25% of cystic neoplasms in pancreas
70s
Surgical resection
183
Mucinous cystic neoplasm
95% in women
Associated with invasive carcinoma
Painless slow growing mass, filled with mucin
Evaluate for malignancy after removal
184
Intraductal Papillary Mucinous neoplasm (IPMN)
Mucin producing intraductal neoplasm, more in males
Pancreatic head
Involve large pancreatic duct
185
Solid pseudopapillary neoplasm
Young women
LArge circumscribed, solid and cystic
Neoplastic cells in sheets/papillary projections
Activating mutation of B catenin
186
Pancreatic cancer
Infiltrating pancreatic ductal adenocarcinoma = 4th leading cause of cancer death
Highest mortality rate
Smoking, fat, chronic pancreatitis, diabetes, alcohol
187
Pancreatic intraepithelial neoplasia
Precursos of pancreatic cancer
188
Types of cholelithiasis
1. Cholesterol (80%), western
2. Pigment (20%), non western
189
Cholesterol stone pathogenesis
Cholesterol normally soluble in bile
High cholesterol concentrations --\> precipitates out and forms crystals --\> crystals aggregate and form stones
190
Contributing factors to cholesterol stone formation
Biliary hypersecretion of cholesterol
Gallbladder hypomobility - promotes nucleation
Altered bile composition
Mucus hypersecretion - traps crystals
191
Cholesterol stone risk factors
Native American
Age
Female
Estrogen
Obestiy
Gallbladder stasis
Fam hx
FEMALE FAT FORTY FERTILE
192
Pigment stones: Composition and pathogenesis
Mostly bilirubin calcium salts
INfection of biliary tract --\> release of beta glucoronidases --\> hydrolyze bilirubin glucoronides --\> bilirubin release
Intravascular hemolysis --\> increased biliary excretion of conjugated bilirubin
193
Risk factors for pigment stones
Hemolytic syndromes
Bacterial/parasitic infection of biliary tract
194
Cholesterol stone morphology
YELLOW
Finely granular, hard external
Radiolucent if pure cholesterol
Radiopaque if mixed with Ca
195
Pigment stone morphology
Black - Sterile sites. Small, numerous, soft, radiopaque
Brown - Infected bile ducts. Laminated, radiolucent
196
Cholesterolosis
Cholesterol esters accumulate within lamina propria
197
Acute Calculus Cholecystitis - Definition, presentation, labs, treatment
Most common complication
Chemical irritation and inflammation caused by obstruction of gallbladder neck/cystic duct
RUQ pain, fever, tachycardia
Jaundice - bile duct obstruction
Labs: Mild WBC increase, mild ALP increase
Immediate surgery
198
Acute acalculus cholecystitis: Definition, signs/symptoms, prognosis
No gallstones, critically ill patients (surgery, trauma, sepsis, burns)
Related to ischemia due to decreased flow through cystic artery
Fatal if not recognized early
199
Chronic Cholecystitis
May or may not be associated with prior attacks
\>90% associated with gallstones
Recurrent RUQ pain, nausea, vomiting, intolerance for fatty foods
200
Acute cholescystitis complications
Empyema - Lumen filled with pus, gallbladder wall thickened, edematous, hyperemic
Gangrenous cholecystitis - Necrotic gallbladder wall, prone to perforation
Emphysematous cholecystitis - Gas in gallbladder due to gas forming organisms
201
Chronic cholecystitis complications
Porecelain gallbladder - dystrophic calcification within gallbladder wall
Xanthogranulomatous cholecystitis - Shrunken nodular gall bladder, lipid laden histiocytes
Hydrops - Atrophic, chronically obstructed gall bladder filled with clear secretions
202
Choledocolithiasis
Stones within biliary tree - 10% gallstone patients
Symptoms from:
Duct obstruction, pancreatitis, cholangitis, hepatic abscess
203
Cholangitis
Infection of bile ducts
Spread into intrahepatic ducts = ascending cholangitis
Suppurative cholangitis - purulent bile fills bile duct and extends to hepatic parenchyma --\> abscess
204
Commone cholangitis pathogen
Gram - bacteria
E coli
Klebsiella
Bacteroides
205
Charcots Triad
Fever
Jaundice
RUQ pain
CHOLANGITIS
206
Biliary atresia
Most common cause of death from liver disease in early childhood
Rapidly progressive biliary cirrhosis
Fatal at age 2 if not treated
207
Choledochal cysts
Congenital dilations of common bile duct
Increased risk of bile duct carcinoma
208
Gall bladder carcinoma
Female predominance
Stone/infections may be risk factors
Poor prognosis, most are incidental findings
Growth patterns:
1. Infiltrating - irregular, diffuse thickening of wall, firm
2. Exophytic - Irregular, cauliflower like mass growing into lumen
209
Extrahepatic bile duct carcinoma
Elderly patient with jaundice
Risk factorsL Biliary tree infections, primary sclerosing cholangitis, IBD
Poor prognosis
210
Amylose
Plants
Linear alpha 1,4 bonds
211
Amylopectin
Amylose + 1,6 bond branches
212
Glycogen
Amylopectin + branches
213
Cellulose
Linear Beta 1,4 bonds
214
Mouth digestion
Salivary amylase
Cleaves amylopectin
215
Sucrase-Isomaltase complex: Enzymes, substrate, product
Sucrase: Sucrose --\> Fructose+glucose
Maltase: Maltose/Maltotriose --\> Glucose
Isomaltose: A limit dextrins --\> glucose
216
Glucose/Galactose enterocyte absorption protein
SGLT1
217
Fructose enterocyte absorption
Glut5
218
Lipid Digestion Steps
Minor Digestion
Major Digestion
Bile acid
Passive absorption
Re esterification
Assembly and export
219
lingual lipase: Action site, substrate, product
Mouth/stomach
Substrate: TAG w/ medium chain FA
Product: FFA + DAG
220
Pancreatic LIpase: Action site, substrate, product
SI lumen
TAG with long chain FA
FFA + 2MG
221
Phospholipase A2: Action site, substrate, product
SI lumen
Phospholipids
Unsaturated FFA + Lysolechthin
222
Lipoprotein Lipase: Action site, substrate, product
Capillary wal
TAG in chylomicron of VLDL
FFA + Glycerol
223
Insulin function
Promotoes anabolic processes
Inhibit catabolic processes
Counter regulatory to glucagon, epi, cortisol
Stores glycogen, TAG, protein
Increase AA/glucose transport into muscle and fat
224
Insulin production steps
1. mRNA production
2. Preproinsulin synthesized, uptake into ER, signal peptide cut
3. Proinsulin transported ot golgi
4. Proinsulin --\> insulin, C peptide removed
5. Insulin stored
6. Glucose --\> Ca contraction of microfilaments
7. Granule formation w/ membrane
225
Glucagon processing in pancreas
Preproglucagon --\> Proglucagon (signal peptide cut) --\> Glucagon (Golgi proteases)
226
Intestinal glucagon: Stimulus and processing
Stimulated by high AA
Proglucagon --\> Glicentin + GLP-1
Increase insulin, decrease acid secretion
227
Glucose signaling
Glucose binds --\> metabolized --\> ATP activates Ca channels --\> Immediate Insulin secretion
Glucose binds --\> metabolized --\> DAG activates PKC --\> Increase insulin synthesis
228
Insulin, Ca, Calmodulin
Calcium binds to calmodulin --\> CAM kinase activated --\> Increased insulin synthesis
229
Parasympathetic control of insulin
Ach --\> Increase insulin secretion via increased Ca and increased PKC
230
Sympathetic control of insulin secretion
Alpha2 receptors --\> decrease cAMP --\> decrease secretion
Beta 2 receptors --\> increase cAMP --\> increase insulin secretion
NET EFFECT: Decreased
231
Glucagon and GLP on insulin secretion
Both increase cAMP, small effect though
Glucagon: Acts in concert with insulin for normoglycemia. fine tuning control
GLP1: Active with AA's, increase insulin for increased AA uptake by liver for gluconeogenesis
232
Glucagon stimuli
Hypoglycemia - Most potent stimulus
Promotes liver glucose formation: Glycogenolysis --\> gluconeogenesis
Epinephrine increases secretion - fight or flight
233
Insulin and Glucagon response: Elevated blood glucose
Insulin: increase
Glucagon: Decrease
234
Insulin and Glucagon response: Amino Acids
Insulin: Increased
Glucagon: Increased
235
Insulin and Glucagon response: Ketones
Insulin: Increase
Glucagon: No effect
236
Insulin and Glucagon response: GI Peptides
Insulin: increase
Glucagon: No effect
237
Insulin and Glucagon response: SNS catecholamines
Insulin: Decrease
Glucagon: Increase
238
Insulin and Glucagon response: Somatostatin
Insulin: decrease
Glucagon: Decrease
239
Insulin actions
Synthesis/storage of glycogen, fats, TGs
Activate capillary lipoprotein lipase
Increase amount and activity of liver glucokinase
Boost glycogen synthase activity
Maintain protein balance
240
Insulin signal transduction
Insulin binds --\> 1st TyrK activated --\> 2nd TyrK phosphorylated --\> 1st TyrK phosphorylated --\> Activate Glut channels + Dephosphorylate metabolism enzymes
241
GLUT activation signal transduction
Active IRTK --\> Activate docking protein --\> p85/pI3K --\> PIP3 --\> PDK --\> PKB --\> Signals golgi to traffic GLUT4 to membrane
242
Metabolism inhibition via insulin
Active IRTK --\> PLC active --\> GPI to IPG --\> Active protein phosphatase --\> Dephosphorylate glycogen synthase, glycogen phosphorylase, phosphorylase kinase
243
Metabolic Syndrome
Potential risk to develop Type II DM and CV disease
Glucose tolerance, obesity, HTN, HLD
Insulin sensitivity common
244
Role of fatty acids and insulin sensitivity
Circulating fats induce resistance by replacing glucose as key fuel, alter downstream signaling
245
Proinflammatory cytokines and insulin sensitivity
Trigger inflammation associated with metabolic syndrome
TNFa: Hypertriglyceridemia in obesity
IL6: Increase hepatic output of VLDL
Resistin: Prevents adipocytes from becoming larger, causes insulin resistance
246
Progression of type II DM
Insulin resistance --\> hyperglcemia --\> Hyperinsulinemia --\> increased pancreatic B cell demand --\> Decrease insulin response --\> Worse hyperglycemia --\> increased demand --\> Ultimate inadequate response
247
Type II DM inadequate insulin secretion? Glucose toxicity theory
Hyperglycemia --\> glucose toxicity
Beta cells over taxed --\> under expression of GLUT 2, decreased glucokinase transcription, desensitization
248
Type II DM insulin inadequate: Lipotoxicity
Excess fats --\> lipotoxicity
Obesity blunts glucose response
Altered mitochondrial metabolism of pyruvate = decreased ATP
Induction of uncoupling protein --\> decreased OxPhos
249
Lipotoxicity and amylin theory
Increased FA --\> amylin
Amylin reduces post prandial glucagon secretion --\> diminish hepatic glucose output --\> Reduce hyperglycemia risk
High fat diet --\> Increased amylin --\> Replace cell mass/barrier/reduce function/impair insulin secretion
250
Type I DM
Absolute deficiency of insulin secondary to auroimmune destruction of islet B cells
Failure of tolerance to self
Autoantibodies to B cells
251
Type II DM
Relative deficiency of insulin
Inadequate secretory response by B cells in face of hyperglycemia
Insulin resistance --\> B cell dysfunction
252
Advanced Glycosylation End Products
Form when nonenzymatic rxns occur between intracellular glucose and amino products, accelerated in hyperglycemia
AGE receptor mediated events --\> proinflammatory cytokine release, ROS generation, proliferation of cascular endothelium and ECM
AGE's can cross link to ECM --\> decreased vascular elasticity
253
DM and microvascular disease
Hyperglycemia activates PKC --\> VEGF production and neovascularization of diabetic retinopathy
PKC increases vasoconstrictors and decreases dilators
Proinflammatory cytokines and profibrogenic factors produced --\> Inflammation and increased BM deposition
Glutathione production --\> increased susceptibility to oxidative stress
254
DM and macrovascular disease
Accelerated atherosclerosis in aorta and large/medium arteries
MI due to infarction
Hyaline arteriolosclerosis associated with HTN
255
Diabetic microangiopathy
Diffuse thickening of basement membranes
Most evident in skin, skeletal muscle, retina, renal glomeruli, medulla
Diabetic capillaries are leakier
Underlies development of diabetic neuropathy, nephropathy, retinopathy
256
Diabetic nephropathy
Glomerular lesions, renal vascular arteriolosclerosis, pyelonephritis
Capillary BM thickening
Diffuse mesangial sclerosis
257
Nodular glomerularsclerosis
Nodules of matrix material present in glomerular periphery
Hyalinosis of afferent/efferent arterioles
258
Type I DM Clinical features
Polyuria, polydipsia, polyphagia, ketoacidosis
Insulin deficiency results in catabolic state with decreases assimilation of glucoe into cells
Intracellular hyperosmolality = polydipsia
259
Ebb phase of shock: Definition and purpose
Early post trauma period of hypotension and decreased energy consumption
Protective response within first 24hrs to maintain perfusion --\> inadequate perfusion so body switches to anaerobic metabolism --\> acidosis
260
Ebb phase hormonal changes
Increase in catabolic hormones: Glucagon, Cortisol, Epi
Decrease in anabolic hormones: Insulin, sex hormones
Protein metabolism, increase glyogenolysis, gluconeogenesis, lipolysis
261
Flow phase in shock: definition and purpose
Follows Ebb phase with proper resucitation
Repair of damaged tissues, negative nitrogen balance, increased energy consupmtion
Highly catabolic with increased protein degradation
Hyperglycemia results b/c of peripheral insulin resistance of non damaged tissues
262
Strategy of care in Ebb phase
Treat cause of hypovolemic shock, stop progress of Ebb phase
* Stop hemorrhage
* Administer oxygen
* Administer IV volume
* Repair injury
263
Recovery phase treatment strategy
Multi team approach
Prevent developing comlications
Prevent hospital acquired infections
Nutritional supplementation
Strengthen therapy/rehabilitation
264
Fed state: Origin of glucose, tissues using glucose, brain fuel
Origin: Exogenous
Tissues using glucose: All
Brain fuel: Glucose
265
Post absorptive phase: Origin of glucose, tissues using glucose, brain fuel
Origin: Hepatic glycogen, gluconeogenesis
Tissues: All except liver. Muscle/adipose at lower rates
Brain fuel: Glucose
266
Early fasting phase: Origin of glucose, tissues using glucose, brain fuel
Origin: Gluconeogenesis
Tissues using glucose: Brain and RBCs, small amount by muscle
Brain fuel: Glucose
267
Prolonged starvation: Origin of glucose, tissues using glucose, brain fuel
Origin: Gluconeogenesis
Tissues using glucose: Brain at diminished rate, RBCs
Brain fuel: Ketone bodies
268
Brunners Glands
Mucus secreting glands in duodenum
Protect against acid load coming from stomach
269
Crypts of Lieberkuhn
Located in crypts of small intestine
Contain pluripotent stem cells for cell regeneration
270
Stimulus for intestinal stem cells
CCK
271
Active water secretion in intestine
cAMP activated CFTR protein, pumps out Cl
Water follows
Cholera mechanism
272
Normal inducer of intestinal active water secretion
VIP
273
Normal water flow in intestine
Water absorption and HCO3 secretion (Cl/HCO3 antiport)
274
Intestinal Na absorption
Majority occurs in jejunum (80%)
1. Na/H antiport
2. Na/substrate co transport
3. Na channel
275
Intestinal sodium absorption by location
Na/H: High in proximal intestine, low in colon
Na/substrate co transport: Decrease along length of intestine
Na channel: Most important in distal colon
276
Aldosterone in intestine
Increases number of Na channels --\> Regulate water absorption
277
Cl absorption
Proximal intestine: Paracellular to account for electrochemical gradient created by Na absorption
Distal colon: Cl/HCO3 antiport. HCO3 neutralizes H created by bacteria
278
K absorption in intestine
Completely passive absorption
Proximal - absorption b/c solvent drag
Distal - No solvent drag, slower absorption, but driving force increased b/c water absorption = increased [K luminal]
279
Pathophysiology of diarrhea
1. Motility: Increased vs decreased propulsion
2. Absorption: Malabsorption disorders
3. Seretory: Cholera, VIPoma
280
Castor Oil
In low doses, induces crypt cell AC --\> opens Cl channels --\> laxative action
281
Magnesium sulfate
Osmotic laxative
Not absorbed well because of charge --\> induce laxative action
282
Bulk forming laxatives
Bran, Psyllium, methylcellulose
Contain non digestible fibers --\> cause motility and defecation reflex
Safest and preferred
283
Loperamide
Opioid agonist
Reduce motility and GI contraction
284
Diphenoxylate
Synthetic opioid w/ atropine to prevent abuse
Overdose can cause respiratory depression (CNS stimulation)
285
Bismuth Subsalicylate
Anti diarrheal
May bind bacterial toxins and prevent cAMP induced diarrhea
286
Cholestyramine
Binds bile acids and prevents diarrhea caused by inadequate bile acid uptake
Chronic therapy can interfere with fat digestion --\> steatorrhea
287
Prokinetic drugs used for...
GERD
Gastroparesis
Refractory constipation
288
Dopamine and GI motility
Dopamine inhibits GI motility
289
Metoclopramide
Dopamine antagonist (5HT3) --\> Increase motility
5HT4 agonist, ganglionic stimulant --\> increase motility
Prokinetic and anti emetic
Crosses BBB --\> Sedation, anxiety, dystonic
290
Bethanechol
M2 agonist --\> Promote motility
291
Domperidone
Dopamine antagonist
Ganglionic stimulant
Prokinetic, antiemetic
NO BBB CROSSING
Headaches, gynecomastia
292
Baclofen
GABA agonist --\> Reduces LES relaxation
CNS effects --\> Drowsiness, dizziness
293
Splanchnic circulation
ORgans fed by celic, SMA, IMA
294
Segmental control of alimentary blood flow
Regulated by tissue activity
Distension/movement in region --\> increased motility and elevated blood flow
295
Transmural blood flow of alimentary canal
Blood flow to different intestinal layers is highest in those with most activity
296
Post prandial hyperemia
Blood flow to alimentary canal increases substantially floowing meal
Buildup of metabolic end products --\> vasodilation to increase O2 availability and remove absorbed nutrients
297
Countercurrent exchange in intestinal villus
Oxygenated blood flow in and venous blood flow out of villus is parallel
O2 flows from arteriole to venule down concentration gradient directly
298
Implications of villus countercurrent exchange
O2 delivery impeded, can lead to ischemic hypoxia
Increased osmolarity as blood reaches tip which contributes to increased water absorption
299
Protective mechanisms in alimentary canal
HCl in stomach kills bacteria
Ileal-Cecal sphincter - unidirectional flow
MMC - Bacteria remains in colon but material removed from stomach/SI during inter digestive periods
GALT - Dendritic cells and liver kuppfer cells
300
Factors affecting alcohol absorption
COncentration of alc
Irritant properties of alc
Type of beverage
Blood flow to site of absorption
Food
Rate of ingestion
301
Food effect on alcohol
Food delays gastric emptying and slow absorption rate
Food boosts rate of alcohol metabolism
Return to zero alc concentration is earlier
Hepatic first pass is greater
302
Alcohol Distribution
Distributed to tissues in proportion to H2O content
Not absorbed by fats (women have more fat --\> higher BAC b/c not absorbed)
303
Alcohol first pass gastric metabolism
Mediated by gastric alcohol dehydrogenase
Women lack this enzyme
Low in alcoholics
304
Metabolism of alcohol
Alcohol --\> Acetaldehyde (ADH) --\> Acetate (Aldehyde dehydrogenase)
Each step NAD --\> NADH
305
Cytochrome metabolism of alcohol
CYP2E1 metabolizes alcohol at BAC\>.08%
Induced in chronic alcohol consumption
306
Genetic polymorphisms in alcohol metabolism
ADH isoforms can result in faster metabolism --\> lower risk for heavy drinking and alcohol problems
ALDH variations (common in asians) --\> problems with aldehyde breakdown = severe reactions
307
Fomepizole
ADH inhibitor
Used in management of methanol and toxic alcohol poisonings
308
Disulfiram
ALDH inhibitor
Noxious effects due to increased aldehyde in blood
309
Metabolic effects of alcohol metablism
Increased NADH/NAD ratio
Inhibits: Glycolysis, Krebs, PDH, LDH, Fatty acid oxidation
310
Metabolic consequences of heavy alcohol use
Hypoglycemia: Heavy drinking while fasting. Glycogen stores gone and Alc inhibits gluconeogenesis
Ketonemia: Increase acetone formation and Acetoacetate --\> BhydroxyButarate b/c high NADH
Lactic Acidosis: Increase lactate formation, LDH
Hyperuricemia: Lactic acidosis competes with uric acid for renal tubular secretion --\> uricemia
311
Alcohol and lipid metabolism
Alcohol intake --\> Decreased NAD --\> Beta oxidation of fatty acids cannot be completed
Increased NADH --\> Triglyceride synthesis --\> Hypertriglyceridemia
312
Acute molecular neuro effects of alcohol
Increased dopamine release
Increased GABA activity --\> sedation, motor dysfunction
Decreased Glutamate receptor activity
313
Chronic alcohol use neuroadaptation
Decreased dopamine release and increased receptor expression
Decreased GABA receptor expression
Increased glutamate release
Increased NMDA expression
314
Alcohol and GI tract
Irritant + gastric acid production = gastritis and bleeding
Ulcerations
Vomiting due to irritation
Pancreatitis
Upper GI hemorrhage
Mallory Weiss tears via vomiting
315
Alcohol and liver
1. Hepatic Steatosis
2. Alcoholic hepatitis
3. Alcoholic cirrhosis
316
Alcohol and hematopoetic system
Anemia - secondary to GI blood loss, vitamin deficienies, bone marrow depression
Alcohol induced thrombocytopenia, decreased clotting factor production
317
FAS facial abnormalities
Short palpebral fissures
Smooth philtrum
Thin upper lip
318
Alcohol and women
Women tend to have higher BAC b/c of no gastric alcohol dehydrogenase and higher body fat --\> smaller volume of distribution
Women develop alcohol induced liver disease faster
More likely to develop alcoholic hepatitis and die or cirrhosis
319
Alcohol use disorder
Cluster of behavioral and physical symptoms
At risk drinkers
3 fold increase in mortality
Symptoms include withdrawal, tolerance, craving
320
Drug class for alcohol withdrawal management
Benzos
321
Alcohol and warfarin
Alcohol inhibits CYP450 --\> enhanced warfarin action
322
Alcohol and acetominophen
CYP2E1 induction --\> enhanced production of NAPQI --\> liver toxicity
323
Alcoholic steatosis
Extensive fat accumulation, reversible
Microvesicular fat --\> Macrovesicular fat
Liver can enlarge
324
Acute alcoholic hepatitis
Liver swollen, edematous, hepatocytes contain Mallory bodies
Widespread necrosis and PMNs
Pericentral fibrosis
Can lead to cirrhosis
Hepatocyte injury with balooning degeneration
325
Alcoholic cirrhosis
10-15% of alcoholics
Classically micronodular
326
Liver cirrhosis
Parenchymal necrosis
Destroyed liver architecture
Nodular regeneration often with fobrosis
Anorexia, weight loss, ascites, gonadal atrophy, gynecomastia (increased estrogen)
Hepatorenal syndrome (severe)
327
Post hepatic causes of Portal HTN
Severe right sided HF
Budd Chiari
Cosntrictive pericarditis
Hepatic veno occlusive disease
328
Intrahepatic causes of portal HTN
Cirrhosis
Shistosomiasis
Fatty change
Sarcoidosis
Idiopathic
329
Prehaptic causes of portal HTN
Portal vein thrombosis
Splenomegaly
AV fistula
330
Biliary stasis
No necrosis
Caused by anabolic steroids, progesterone
331
Acute hepatic necrosis causes
Carbon tetrachloride
Halothane
Paracetamol
332
Chronic parenchymal damage causes
Methyldopa
Methotrexate
Isoniazid
333
Reyes syndrome
fattty change in liver with encephalopathy
Affects children after flu like symptoms
Microvesicular steatosis, cerebral edema
Biochemical derangement/iral infection affecting mitochondrial metabolism
334
Pre-eclampsia/eclampsia and liver
Small patches of hemorrhage and infarct
Hepatic disease is common --\> Hemolysis, elevated liver enzymes, low platelets
335
Acute fatty liver of pregnancy
Wide range disease
3rd trimester
Biopsy confirmation
Termination of pregnancy
