1
Q
in the GI system, what is the breakdown of food and fluids facilitated by?
general
A
enzyme
2
Q
majority of molecular absorption into cells occurs where?
general
A
small intestine
3
Q
what are the 5 roles of the GI system?
A
- mechanical processing and movement
- secretion
- digestion
- absorption of nutrients
- elimination
4
Q
what are the accessory organs of the GI system?
A
- salivary glands
- liver
- gallbladder
- pancreas
5
Q
the pancreas produces and secretes what two things?
general
A
enzymes
bicarbonate - neutralize stomach contents
6
Q
identify and describe the layers of the GI system from innermost to outermost
A
- innermost - mucosa - epithelial cells in direct contact with the lumen
- submucosa - connective tissue containing blood vessels, lymph vessels and nerves
- muscularis - smooth muscle responsible for movement and motility
- outermost - serosa - connective tissue that provides anchorage of GI structures
7
Q
what layer of the GI system contains the lamina propria?
A
mucosa
8
Q
what layer of the GI system contains the peritoneum?
A
serosa
9
Q
what are the 5 main GI hormones?
A
- gastrin
- cck - cholecystokinin
- secretin
- gip - gastric inhibitory peptide
- ghrelin
10
Q
describe gastrin:
* secreted by
* secretion trigger
* what it causes
A
- secreted by mucosal cells in stomach
- secreted in response to stomach distrention or partially digested substances
- causes increased gastric motility and relaxation of pyloric and ileocecal sphincters (promote stomach emptying)
11
Q
describe CCK:
* secreted by
* secretion trigger
* what it causes
A
- secreted by jejunum
- secreted in response to fat
- causes contraction of gallbladder and pancreatic secretions
12
Q
describe secretin:
* what it causes
A
- neutralizes gastric secretions
13
Q
describe GIP:
* secreted by
* secretion trigger
A
- secreted by upper portion of small intestine
- secreted in response to fat in chyme and carbohydrates
14
Q
describe ghrelin:
* secreted by
* secretion trigger
* what it is counteracted by
A
- secreted by stomach
- increases appetite, stimulates GH secretion, produces weight gain
- counteracted by leptin
15
Q
what are the 3 physiological characteristics of movement through the GI system?
A
- peristalsis - progressive movement that propels material forwards
- segmental contractions - to keep contents constantly moving and facilitate mechanical breakdown
- sphincters - rings that separate sections to promote one way movement
16
Q
identify and describe the defense mechanisms of the GI system
A
- mucous - move pathogens and prevent direct contact with epithelial layers
- muscular layer and peristalsis - move items down and prevent pathogens from stopping and invading
- stomach acidity - antimicrobial effects to prevent tract colonization
- GI bile - create a hostile environment
- microbiome - add a protective layer, compete for nutrient resources, produce helpful components (i.e. vit K - coagulation)
- GALT - adaptive response
17
Q
define dysphagia
A
difficulty swallowing
18
Q
define gastritis
A
inflammation of the stomach lining
19
Q
define gastroenteritis
A
inflammation along the GI tract
20
Q
define enteritis
A
inflammation of the colon and small intestine
21
Q
define enterocolitis
A
inflammation of the colon and small intestine
22
Q
define colitis
A
inflammation fo the colon
23
Q
define hemmorhagic colitis
A
bloody diarrhea
24
Q
describe constipation by:
* definition
* causes
* complications
* preventative things
A
- definition: small, infrequent, or difficult bowel movments, less than 3 times a week
- causes: low fiber, lack of exercise, aging (slowed peristalsis), motility impacting conditions (diverticulitis, obstruction)
- complication: fecal impaction
- preventative thing: cellulose
25
identify the 4 types of diarrhea
1. osmotic
2. secretory
3. inflammatory/exudative
4. motility related
26
describe osmotic diarrhea
diarrhea when nutrients are inadequately or poorly absorbed
27
describe secretory diarrhea
diarrhea caused by toxins that stimulate intestinal fluid secretion and impair absorptions
* can lose 1L or more a day
* i.e. cholera
28
describe inflammatory or exudative diarrhea
diarrhea caused by inflammation of the mucosal lining
* pus like formation can cause white flakes/patches
29
describe motility related diarrhea
rapid movement of food through tract - decreased transit time of chyme with absorptive surfaces
30
define dysentery
presence of blood in loose or liquid stools
31
what are some means of diagnosis, treatment, and prevention of GI pathologies?
* diagnosis: S&S assesment, imaging, fecal samples
* treatment: alleviate symptoms, oral rehydration therapy
* prevention: eliminate aggravators, proper health and hygiene, sanitation and food handling
32
what function do antacids have in treating GI pathologies?
reduce excessie acidity
33
what function do antiemetics have in treating GI pathologies?
relieve vomiting from drugs, motion sickness, or other therapy
34
what function do laxatives/enemas have in treating GI pathologies?
facilitate bowel movement to treat acute constipation
35
what function do antidiarrheals have in treating GI pathologies?
reduce peristaltic activity (motility) and relieve cramps
36
what function do coating agents have in treating GI pathologies?
enhance gastric mucosal barrier against irritants such as NSAIDs
37
what function do anticholinergic drugs have in treating GI pathologies?
reduce pns activity, reduced secretions and motility
38
what function do histamine blockers have in treating GI pathologies?
useful in gastric reflux
39
what function do proton pump inhibitors have in treating GI pathologies?
reduce gastric secretion
40
describe gastric ulcers by:
* definition
* common sites
* potential causes
* variabiltiy (traits that can be variable)
* definition: lesions in the mucosa
* common sites: stomach, duodenum, esophagus
* causes: stress, foods, meds, H. pylori
* variable traits: number, size, location, severity, causes
41
severity of a peptic/gastric ulcer can vary based on what?
size and depth
42
a true ulcer is a lesion into what layer of the GI lining?
submucosa
43
a pentrating ulcer goes into what layer of the GI lining? what can possibly occur with this type of ulcer?
* into the serosa
* can cause pain and bleeding - indicative when blood in stool
44
describe H. pylori including:
* gram state: + or -
* motility
* spore forming?
* transmission
* other implications
* gram negative
* motile via multiple polar flagella
* non spore forming
* transmitted via fecal-oral or oral-oral
* also implicated in stomach cancer and gastritis
45
what are some things that being H pylori positive increases risk of?
* gastric cancer
* MALT lymphoma
* gastric ulcers
* duodenal ulcers
* functional dyspepsia (indigestion)
46
describe the pathogenesis of H. pylori
* enabled by **urease** : neutralizes stomach pH
* adheres to gastric epithelial cells
* LPS and antigens stimulate immune response and inflammation
* slowed ulcer healing
* high recurrence rate
47
what are the 4 major virulence factors of peptic/gastric ulcers?
1. LPS
2. TFSS/T4SS
3. Vac A
4. Cag A
48
describe TFSS/T4SS
| GI system
* secretion system
* allows pathogen to secrete virulence factors into host
* decreases host function and may induce apoptosis (contribute to erosion)
49
describe Vac A
| GI system
* pore forming cytotoxin
* targets mitochondria
* reduces membrane potential and compromises ATP synthesis
* cytochrome c leakage - caspase activation - proapoptotic
50
describe Cag A
| GI system
* activate of MMP that can facilitate erosion
* alter cell-cell and cell-basement leakage
* e-cadherin or beta-catenine disruption
51
what are some clinical manifestations of peptic and gastric ulcers?
* localized abdominal pain and burning
* nausea - vomiting and loss of apetite
* sometimes bleeding
52
what are some potential complications of peptic/gastric ulcers?
* hemorrhages: via erosion of blood vessels
* perforation: complete erosion that allows chyme to enter peritoneal cavity
* obstructon: via scar tissue formation (more likely in duodenum and esophagus)
53
what is GERD (gastroesophageal reflux disease)?
periodic reflux of gastric contents into the distal esophagus
54
what does the severity of GERD depend on? what can GERD cause?
* severity depends on LES competense, frequency, and amount of acid
* may cause erosion and inflammation
55
what are the clinical manifestations of GERD and some aggravating factors?
* manifestations - heartburn, chest pain, dysphagia
* aggravating factors - caffiene, spicy food, fatty food, alcohol, smoking, some meds
56
since some clinical manifestations of GERD include heartburn and chest pain it is often confused for what?
angina
57
what is GERD often seen in conjunction with?
hiatal hernia
58
what is a hiatal hernia?
when the uppermost portion of the stomach protrudes into the thoracic cavity through the hiatus (opening in the diaphragm)
59
what are some potential causes of a hiatal hernia?
* incompetent sphincter
* diaphragm tone
* abdominal pressure - full stomach, obesity, pregnancy
60
what are some risks/complications associated with hiatal hernias?
perforation/rupture into thoracic cavity due to:
* contents (bacteria and food) within the sac causing aggravation
* feedforward mechanism of inflammation causing pressure on the sac
61
what are some things that impact the tone of the LES?
* delayed gastric emptying
* increased transient LES relaxations
* loss of secondary peristalsis
* increased acidity
62
what are some complication risks with esophageal reflux disease (6)?
1. **stricture** - stiffness caused by scar tissue formation
2. **pain**
3. **obstruction** - food and inflammation preventing passage of food from the esophagus to stomach
4. **perforation**
5. **hemorrhage** - dependent on depth may be internal or external
6. **pneumonia** - contents rise high enough that they go down the trachea into the lungs
63
what is barrett's esophagus?
change in esophageal cell morphology from squamous to columnar epithelieum
64
how can barrett's esophagus be diagnosed? can it be reversed?
* diagnosis - via endoscope
* reversible - yes with removal of irritant
65
what type of cancer does barrett's esophagus increase the risk of?
adenocarcinoma (glandular epithelial cells)
66
what are the 2 diseases within IBD?
1. ulcerative colitis (UC)
2. crohn's disease
67
define IBD by:
* typical diagnosis time
* disease course (general)
* cause
* diagnosis time - childhood
* disease course - variable periods of exacerbation and remission
* cause - idiopathic (unknown because multifactoral)
68
compare/contrast IBD and food-borne infectious GI issues in terms of diagnosis and treatment
**IBD:**
* fecal culture - negative
* treatment - cant use antibiotics
**infectious:**
* fecal culture - positive
* treatment - can use antibiotics
69
ulcerative colitis is a chronic inflammatory disease of the mucosa of the ____ and ____.
* rectum
* colon
( distal GI tract )
70
in UC inflammation begins at the base of ____ causing damage and invasion with ____. this results in formation of an ____ within crypts and formation of large ____ in the mucosal layer
in UC inflammation begins at the base of **intestinal crypts** causing damage and invasion with **leukocytes**. this results in formation of an **abcess** within crypts and formation of large **ulcers** in the mucosal layer
71
in ulcerative colitis coalescence of abscesses results in large ulcerations through the ____.
* epithelia barrier
72
what are the clinical manifestations of ulcerative colitis?
* severe lower abdominal cramping
* diarrhea
* rectal bleeding
* hallmark - bloody diarrhea
73
what causes the diarrhea experienced in ulcerative colitis?
* mucosal destruction in colon ->
* decreased ability to absorb water and sodium ->
* excess fluid volume in intestinal contents ->
* excessive fluid loss
74
ulcerative colitis can be related to ____ which can cause developmental delays in youth
low weight
75
is ulcerative colitis associated with an increase or decrease in lumenal diameter?
decrease
76
what are some other names for crohns?
* regional enteritis
* granulomatous colitis
77
in what areas of the GI tract does crohns normally occur (2)?
* terminal ileum of SI
* ascending colon
78
what is crohns and what does it involve (4)?
* chronic inflammation of **all layers** of the intestinal wall
* includes ulcerations, strictures, fibrosis, fistulas
79
what can crohn's result in?
blockage and inflammation of lymphatic vessels
80
what are skip lesions seen in crohn's
* distribution of affected segments alternating with normal segements of bowel
81
what are fistulas seen in crohn's?
* abnormal opening between two structures
* crohns - between the small and large intestine
82
what are some clinical manifestations of crohns?
* intermittent fever,
* soft or semi-formed stool (may or may not have blood - not as severe as UC when not bloody)
83
what comorbidities may be seen in people with crohns?
* anorexia
* weight loss
* anemia
* fatigue (malabsorption and malnutrition)
* delayed growth and sexual maturation in kids
84
what are the main components of crohns disease (3)?
| very broad
* genomic
* immune
* microbiome
85
what are some potential triggering factors in crohns?
* exercise
* smoking
* infection
* envrionment
* hygiene
* diet
* drugs
* stress
86
what are some treatments for ulcerative colitis and crohn's (6)?
1. anti-inflammatory meds
2. anti-motility agents (symptomatic relief)
3. immunotherapeutic agents
4. antimicrobials
5. nutritional supplements
6. surgical resection (extreme)
87
compare and contrast crohns and ulcerative colitis by:
* region affected
* distribution of lesions
* stool
* granuloma?
* fistula, fissure, abscess?
* stricture, obstruction?
* malabsorption, malnutrition?
88
what is the etiology of irritable bowel syndrome?
unclear or variable
89
what are some clinical manifestations of IBS
* lower abdominal pain
* diarrhea/constipation - abnormal bowel movements
* gas, bloating, nausea
* fecal urgency or incomplete evacuation
90
IBS pathogensis is associated with different types. describe **abnormal gastrointestinal motility and secretion**
* diarrhea type: rapid transit time of feces throguh bowel
* constipation/bloating type: delayed transit time of feces through bowel
91
IBS pathogensis is associated with different types. describe **visceral hypersensitivity**
immune system, involvement of activated mast cells and T lymphocytes
92
IBS pathogensis is associated with different types. describe **post-infectious**
low-grade inflammation associated with bacterial enteritis
93
IBS pathogensis is associated with different types. describe **overgrowth of flora**
* causes constipation and bloating due to methane gas production
* imbalance in microbial growth - i.e. with long term use of antibiotics
94
IBS pathogensis is associated with different types. describe **food allergy or intolerance**
certain food antigens may activate a hypersensitive immune response in the mucosa
95
IBS pathogensis is associated with different types. describe **pyschosocial factors**
emotional stress, affecting the nervous system and neuroendocrine pathway
96
what are some treatment techniques for IBS
* laxatives
* fiber supplements
* antidiarrheal medication
* antidepressants
* analgesics for pain
* antipasmodic medication
* serotonin balancing medications
97
define diverticulum
outpouching of the mucosa through the musculature
98
define diverticulosis
symptomatic diverticular disease
99
define diverticulitis
inflammation usually due to diverticulitis stasis
100
what does diverticular disease result from?
* low dietary fiber intake
101
what does diverticular disease result in?
high intraluminal pressure
102
what is diverticular disease associated with symptomatically?
* cramping
* tenderness
* nausea
* vomiting
* slight fever
* elevated white blood cell count
103
what is the primary location of secondary metastasis?
lungs
104
kRas mutations can lead to what types of cancer?
* pancreas
* colon
* billiary tract
* small intestine
* lung
* ovary
* endometrium
105
nRas mutations can lead to what types of cancer?
* skin
* hematopoetic
* autonomic ganglia
106
hRas mutations can lead to what types of cancer?
* savlivary gland
* urinary tract
* cervix
107
32 Ras-GEF genes are associated with what Ras state?
active - bound to GTP
108
14 Ras-GAP genes are associated with what Ras state?
inactive - GTP hydrolysis and GDP binding
109
what is the pathway for the stimulation of grwoth factors and Ras leading to cancer?
1. growth factors
2. Ras
3. Raf
4. MEK
5. ERK
6. proliferation, differentiation, cell survival
110
how can Ras activation be detected?
phosphorylation via immunoblotting
111
what Ras mutation affected basal homeostasis is colonic epithelieum leading to excessive crypt depth?
K-Ras (G12D)
112
polyps are outgrowths that grow into what area? what can they be assesed through?
* grow into the lumenal cavity
* assessed through endoscopy
113
mutations in what genes are associated with colorectal cancer (4)?
1. p53
2. apc
3. smad2
4. smad4
114
what do most colorectal malignancies develop from?
adenomatous polyps
115
what are the two forms of colorectal cancer?
| general
1. sessile
2. pedunculated
116
what are sessile polyps?
* raised protuberance with a broad base
* more consistent size throughout
117
what are pedunculated polyps?
* attached to bowel wall by a stalk narrower than the body of the polyp
* narrow base with longer/narrow head
118
what are the general clinical manifestations of colorectal cancer?
* change in bowel habits
* bleeding
* abdominal pain and discomfort
* fatigue, weight loss, anemia
119
what occurs with colorectal cancer in the transverse colon?
* semisolid stool
* anemia - occult blood in stool
* change in bowel habits
120
what occurs with colorectal cancer in the ascending colon?
* liquid stool
* occult blood in stool or melena
* anemia, fatigue
* late-palpable mass
121
what occurs with colorectal cancer in the descending colon?
* solid stool
* constipation and discomfort
* abdominal fullness and distention
* red or dark blood in stool
* black, tarry stool
122
what occurs with colorectal cancer in the rectum?
* solid stool
* abdominal discomfort and cramps
* ribbon or pellet stool
* incomplete emptying
* red blood on the surface of stool
123
what type of restriction results due to circumferential growth in colorectal cancer?
stricture
124
what are some risk factors for colorectal cancer (9)?
1. genetics
2. familial polyps (FAP)
3. smoking
4. alcohol
5. western diet
6. processed meats
7. obesity
8. sedentary lifestyle
9. chronic irritation or inflammation
125
colorectal cancer can be diagnosed through 3 ways - testing, visual imaging, and screening. identify some diagnosis techniques in each.
* testing: biomarkers, blood tests, genetic tests
* visual imaging: radiograph, ultrasound mri, ct
* screening: endoscope and biopsy
126
what are the major regions of the pancreas?
* head
* neck
* body
* tail
127
what is the exocrine function of the pancreas?
digestive enzyme and bicarbonate secretion
128
the pancrease secretes enzymes including ____ (3), which is stimulated by the hormones ____ (2) and the proteases ____ (3).
* enzymes: amylase, lipase, proteases
* hormones: cck, secretin
* proteases: trypsin, chymotrypsin, carboxypeptidase
129
briefly describe how zymogens are released from pancreatic acinar cells?
zymogen granules fuse with the apical side of the cell and they are released into the duct leading to the small intestine
130
what is teh role of amylase in the pancreas?
split starch and glycogen into disaccharides
131
what is the role of lipase in the pancreas?
split triglycerides into fatty acids and monoglycerides
132
what is the role of trypsin, chymotrypsin, and carboxypeptidase in the pancreas?
split protein into peptides
133
what is the role of nucleases in the pancreas?
split nucleic acids into nucleotides
134
what are the mechanisms present that prevent auto-digestion?
* pro-enzymes
* trypsin activation (needed)
* trypsin inhibitors (SPINK1)
* trypsin inactivation
135
what are the four potential consequences of pancreatic pathophysiology?
1. insufficiency
2. inflammation
3. neoplasms
4. obstruction
136
what can pancreatic insufficiency lead to?
fatty stools (steatorrhea)
137
what can pancreatic inflammation lead to?
autodigestion of the tissue
may be acute or chronic
138
what can pancreatic neoplasm lead to?
* ductal adenocarcinoma
* neuroendocrine carcinoma
139
what can pancreatic obstruction lead to?
stones or fibrosis
140
what are some potential causes of acute pancreatitis?
* alcohol
* gallstone or biliary sludge
* hypercalcemia ot triglyceridemia
* vascular disease (ischemia)
* iatrogenic causes
* hereditary
* structural abnormalities
141
what are the 3 pathogenic mechanisms of acute pancreatitis?
1. duct obstruction - leads to ischemia and acinar cell injury
2. acinar cell injury - release of proenzymes and lysosomal hydrolases leading to acinar cell injury
3. defective intracellular transport - metabolic injury causing intracellular enzyme activation
142
what are the lesions of acute pancreatitis (think: causes of acinar cell injury and activated enzymes) (4)?
1. interstitial inflammation and edema
2. proteolysis
3. fat necrosis
4. hemorrhage
143
what is the pathogenic mechanism in which acute pancreatitis can occur via blocked secretion?
1. block apical secretion
2. proteases activated within acinar cells
3. digestive enzymes enter interstitial space through disrupted junctions or the basolateral membrane
144
what are the three types of blockages in pancreatitis?
1. **blocking pancreatic outflow** - backflow of digestive juices
2. **allows backflow of bile into pancreas** - inflammation and acinar damage
3. **prevents bile and pancreatic secretions** - fatty stool and pancreatic backflow
145
based on IL and cytokine activation what can pancreatitis lead to?
1. vascular leakage
2. acute tubular necrosis
3. acute respiratory distress syndrome
4. shock
5. hypovolemia
146
acute pancreatitis can cause what type of hemorrhage (colour) and what type of necrosis (colour and type)?
* hemorrhae - red-black
* necrosis - yellow-white fat
147
what are the clinical manifestations of acute pancreatitis?
1. epigastric/abdomenal pain radiating to the back (band-like, not localized)
2. abdominal distention
3. low-grade fever
148
what are 6 things that may come back elevated in a diagnostic test if you have acute pancreatitis?
1. serum amylase
2. serum lipase
3. aminotransferases (AST, ALT)
4. alkaline phosphatases
5. bilirubin
6. lipids
149
apart from elevated levels, diagnostic tests for acute pancreatitis may also show what (2)?
1. hypocalcemia (caclium sites of fat necrosis)
2. leukocytosis
150
apart from blood/serum tests what other diagnostic tests can be done?
abdominal x-rays, ultrasounds, or CT
151
what are some treatments (4) for acute pancreatitis?
1. stopping oral intake - reduce pancreatic secretions
2. treatment of electrolyte imbalances
3. analgesics - pain relief
4. endoscopic treatment
152
describe **bacterial infection** as a risk/complication of acute pancreatitis
* antibiotic treatment
* culture of aspirate fluid
* indicative of poor prognosis
153
describe **abscess or hemorrhage surgical treatments** as a risk/complication of acute pancreatitis
* **neurosectomy:** debridement of devitalized tissue
* **pancreatectomy:** major pancreatic resection, typically resulting in drains
154
describe **psuedocyst** as a risk/complication of acute pancreatitis
* collection of fluid within or adjacent to the pancreas
* notable with abdominal fullness/dystention/mass/tenderness
* managed through endoscopic or surgical drainage
155
describe **pancreatic ascites** as a risk/complication of acute pancreatitis
* persistent leak in pancreatic duct into pleural space and mediastinum
* painless and massive
* detected via imaging (ultrasound/ct) or aspirated fluid analysis
* treated through prolonged parenteral nutrition or stent
156
what are the two main causes of acute pancreatitis?
gallstones and alcohol
157
describe interstitial pancreatitis' progression
1. diffused localized inflammation through pancreatic body and tail
2. transient organ dysfunction, acute fluid collections, mortality (<2%)
3. resolution of fluid infilration or pseudocyst
4. resolution
158
describe the progression of necrotizing pancreatitis
1. persistent organ failure, severe acute pancreatitis, mortality (15-20%)
2. sterile necrosis (10% mortality), infected necrosis (30% mortality)
3. walled off pancreatic necrosis
159
briefly describe chronic pancreatitis and it's predisposing factors
* chronic inflammatory lesions in pancreas associated with alcohol intake, does not increase risk for cancer
* predisposing factors: alcohol consumption, idiopathic, hereditary
160
describe the pathogenesis of chronic pancreatitis
* necrosis of exocrine parenchyma (surrounding connective tissue) followed by fibrosis
* leads to calcification and obstructed flow of pancreatic juices
* persistent symptoms secondary to dysfunction over weeks and months
161
describe the mechanism of chronic pancreatitis via hypersecretion
* acinar hypersecretion
* viscous pancreatic secretions
* protein plug formation from inappropriate protein breakdown
162
describe the mechanism of chronic pancreatitis via acinar atrophy
* acinar cells without zymogen granules (unhealthy)
* ductal stricture and fibrosis - no lumenal diameter
* protein plug formation (intraductal)
* may be due to ischemia
* nothing flows out - may cause necrosis
163
what are some clinical manifestations of chronic pancreatitis?
1. diabetes - progressive loss of islets
2. malabsorption - fat, vitamins A, D, E, and K
3. weight loss - poor intake related to pain
4. insidious onset of steady pain
5. nausea
6. 5 years of continual pain before decrease in symptoms
164
what are some complications of chronic pancreatitis?
* pseudocyst
* pancreatic ascites
* obstruction of common bile duct
* portal and splenic vein thrombosis - may lead to GI hemorrhage
* peptic ulcer disease
165
what are some treatments for chronic pancreatitis?
1. pancreatic sphincterotomy - manage stones
2. endoscopic drains of pseudocysts
3. biliary/pancreatic stents
4. whipple procedure
166
despite pancreatic cancer only being about ____% of cancer its ranks ____th among deaths due to malignancies
* 2%
* 4th
167
what is the median survival rate and mortality % of pancreatic cancer?
* 1 year median survival rate
* 95% mortality
168
is metastases in pancreatic cancer common or uncommon? when does it occur in cancer progression?
* common
* occurs early
169
what are some clinical manifestations of pancreatic head tumors?
* jaundice
* malabsorption
* weight loss
170
what are some clinical manifestations of pancreatic tail tumors?
* abdominal pain
* nausea
171
what percent of pancreatic carcinomas are located in the head of the pancreas?
70%
172
how does mutations with the PRSS1 gene lead to hereditary pancreatitis?
constitutively active trypsin leads to protein degradation, inflammation, abnormal phenotypes, and cancer progression
173
what is the most commmon type of pancreatic cancer? what activation/inactivation occurs?
* adenocarcinoma
* KRAS activation, p53 inactivation
174
what type of neoplasia occurs in pancreatic cancer?
* low or high grade intraepithelial neoplasia
175
176
what are some key mutations that occur in pancreatic cancer?
* p16
* tp53
* SMAD4
* BRCA2
177
what are some fibrotic microenvironment features of pancreatic cancer (5)?
1. abundance of ECM
2. excessive active fibroblasts
3. hypoxia
4. low nutrients
5. immune cells
178
what are some metabolic reprogramming feature of pancreatic cancer?
1. glucose and glutamine uptake
2. lipid and protein uptake
179
what are 2 factors that determine pancreatic cancer resectability?
1. arterial/venous involvement
2. metastases
180
describe **stage 1a** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T1
* nodal status: 0
* distant metastases: 0
* median survival (months): 24.1 months
181
describe **stage 1b** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T2
* nodal status: 0
* distant metastases: 0
* median survival (months): 20.6
182
describe **stage 2a** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T3
* nodal status: 0
* distant metastases: 0
* median survival (months): 15.4
183
describe **stage 2b** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T1, T2, or T3
* nodal status: 1
* distant metastases: 0
* median survival (months): 12.7
184
describe **stage 3** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T4
* nodal status: 0 or 1
* distant metastases: 0
* median survival (months): 10.6
185
describe **stage 4** pancreatic cancer by:
* tumor grade
* nodal status
* distant metastases
* median survival (months)
* tumor grade: T1, T2, T3, T4
* nodal status: 0 or 1
* distant metastases: 1
* median survival (months): 4.5
186
what are some clinical manifestations of pancreatic cancer (12)?
1. abdominal pain
2. anorexia
3. weight loss
4. jaundice
5. diarrhea
6. weakness
7. palpable gallbladder
8. constipation
9. hematemesis/melena (dark feces)
10. vomiting
11. abdominal mass
12. migratory thrombophlebitis
187
what are some abnormal lab tests that may occur with pancreatic cancer?
* increased: AST, bilirubin, amylase
* decreased: albumin
188
what does the liver produce? what is its function?
* bile - emulsifies lipids
189
what is the function of the hepatic portal system?
| general
drain blood from the digestive tract to the liver
190
where is the liver located in the body?
right quadrant of the abdomen
191
what are the 3 components of the structure of the liver?
1. hepatocytes
2. lobules
3. sinusoids
192
what is characteristic of the structure of the liver that allows it to filter?
integrated vascular supply (all hepatocytes have contact with vasculature)
193
what is the function of the **hepatic vein**?
transport blood from the liver through the inferior vena cava to the heart
194
what is the function of the **proper hepatic artery**?
deliver oxygenated blood from the abdominal aorta to the liver
195
what is the function of the **hepatic portal vein**?
deliver oxygenated blood from the GI tract to the liver
ingested nutrients and toxins undergo metabolism w/n hepatocytes
196
what is the function of the **hepatic ducts**?
transport bile from the liver to the gallbladder
197
what is the function of the **common bile duct**?
transport bile from the gallbladder to the duodenum (SI)
198
describe bile by its:
* colour
* production site
* released into...
* contents
* function
* acidity
* colour: yellow-green
* production site: liver
* released into: duodenum by sphincter of oddi
* contents: bile salts, bilirubin, cholesterol, triglycerides, phospholipids
* function: emulsifies fat and increase fat absorption (good for fat-soluble vitamins)
* acidity: alkaline (no HCl)
199
what percent of bile acids are recirculated? what percent are synthesized de novo?
* recirculated: 90%
* de novo: 10%
200
what blood vessel carries blood from the digestive tract capillary beds to the liver capillary beds?
hepatic portal vein
201
heptocyte failure can be attributable to what (3)?
1. loss of hepatocyte function
2. disruption of blood flow
3. disruption of bile flow
202
what are some clinical manifestations of hepatocyte failure? (8)
1. jaundice
2. ascites
3. muscle wasting
4. excess blood loss
5. blood protein deficiency
6. vitamin deficiency
7. hormone deficiency
8. glucose imbalances
203
what is jaundice and what is it caused by?
* yellowing of skin and whites of eyes, amber colour urine
* caused by insufficient bilirubin metabolism
204
what is the typical pathway of hemoglobin breakdown?
hemoglobin -> heme + globin
heme -> bilirubin
globin -> amino acids
205
explain how red blood cell aging and destruction occurs
1. enzymatic activity and membrane lipids of rbc decrease
2. mononuclear phagocytes engulf rbc where they are digested by proteolytic and lipolytic enzymes
206
where are the majority of old red blood cells processed?
spleen and liver
207
describe the process of bilirubin metabolism (7 steps)
1. heme - **hemeoxygenase** -> iron + heme (biliverdin)
2. beiliverdin - **biliverdin reductase** -> bilirubin
3. bilirubin and albumin transported to liver via plasma
4. bilirubin uptake into liver
5. bilirubin conjugation via UDP-GT
6. at ER membrane: bilirubin monoglucuronide and diglucuronide generated
7. bilirubin monoglucuronide and diglucuronide excreted through canaliculi
208
within the intestine what does bacterial beta-glucuronidases generate?
urobilinogen
209
describe pre-hepatic jaundice
* excessive rbc destruction
* elevated unconjugated bilirubin levels
210
describe hepatic jaundice
* when there is hepatocyte disease/dmg
* elevated levels of conjugated and unconjugated bilirubin
* liver unable to process bilirubin
211
describe post-hepatic jaundice
* liver unable to process bilirubin
* build up of bile in liver due to obstructed bile flow into gallbladder or duodenum
* elevated conjugated bilirubin
* lightly colored stool (absence of bile)
212
what are some syndromes that explain genetic mechanism of jaundice (5)?
1. dubin-johnson
2. rotor's
2. crigler-najar
3. neonatal hyperbilirubinemia
4. gilbert's
213
describe portal hypertension by its:
* definition
* cause
* result (varices in what locations)
* definition: increased pressure due to impaired blood flow through the liver
* causes: liver tissue degeneration, GI flow congestion
* result: varices - esophageal, gastric, hemorrhoidal, periumbilical
214
describe gastroesophageal varices and what it can lead to
* venous network surrounding the proximal stomach and esophagus
* can rupture and cause GI bleeding
215
in gastroesophageal varices why does the venous pathway dilate?
in response to elevated portal pressure to try and transport blood from splanchnic bed around cirrhotic liver and back to heart
216
describe GI ascites by:
* definition
* causes
* manifestation
* treatment
* definition: accumularion of fluid within peritoneal cavity
* causes: portal hypertension, plasma hypalbuminemia
* manifestation: abdominal distention
* treatment: paracentesis - relieve pressure and allow for assessment
217
what are the two main pathologies of the liver?
hepatitis
cirrhosis
218
what are the 5 main causes of hepatitis?
1. idiopathic
2. alcoholic
3. viral
4. infection elsewhere in the body
5. chemical or drug toxicity
219
describe chronic persistent hepatitis
* chronic low-grade liver inflammation (any cause)
* inflammation confined to portal triads
* no destruction of normal liver structures
* manifestations: asymptomatic or mild, non-specific
220
describe chronic active hepatitis
* progressive, destructive liver inflammation
* lasts more than 6 months
* extends to hepatic lobule (piecemeal necrosis)
* may progress to cirrhosis
* manifestations: fatigue, nausea, malaise, anorexia, ascites, heptomegaly, pain, jaundice
221
what are some structural differences present in liver with chronic injury (ECM)?
* loss of microvilli/fenestration of hepatocytes
* increased fat cells (fatty liver disease) in ECM
* increased rigidity of ECM
222
describe cirrhosis by:
* characterization
* liver state
* result
* association
* testing
* characterization: extensive diffusive fibrosis that causes bile to back up and interferes with blood supply
* liver state: fibrotic, scarred, nodular
* result: permanent alteration of hepatic blood flow and liver function
* association: loss of lobular organization
* testing: liver biopsy and serologic testing
223
describe/define biliary cirrhosis
* inflammation and scarring of liver
* obliteration of bile ductules
* diffuse, widespread fibrosis
* nodule formation
224
describe the 3 stages of cirrhosis (alcoholic liver disease)
**1. intial - fatty liver**
* liver enlargment
* asymptomatic and reversible
**2. second - alcoholic hepatitis**
* inflammation and cell necrosis
* fibrous tissue formation - irreversible
**3. third - end stage cirrhosis**
* fibrotic tissue replaces normal tissue
* little normal function
225
describe alcoholic fatty liver
* fat accumulation in liver cells
* more fat delivered than can be metabolized by hepatocytes
* mild, asymptomatic, liver enlargment, abdominal discomfort, portal hypertension
226
describe alcoholic hepatitis
* active inflammation of the centrilobular region of the liver
* neutrophilic infiltration and intracellular inclusions (mallory bodies)
227
what are some functional losses with cirrhosis
| never gonna get them all - moreso for cntrl f
* decreased removal/conjugation of bilirubin
* decreased bile production
* impaired digestion and absorption of nutrients
* backup of bile in liver
* decreased production of blood-clotting factors
* imapired glucose/glycogen metabolism
* impaired ammonia -> urea conversion
* decreased inactivation of hormones and drugs
* decreased removal of toxic substances
* blockage of blood flow through liver = portal hypertension
* spleen congestion = hemolysis
* inadequate storage of iron and vitamin B12
* esophageal varices and potential homorrhage
* ascites causing abdominal distention and pressure
228
what are some initial clinical manifestations of cirrhosis?
* often mild/vague
* fatigue, anorexia, weight loss, anemia, diarrhea
* dull aching pain
229
what are some clinical manifestations of advanced cirrhosis
* ascites and periperhal edema
* increased bruising
* esophageal varices
* jaundice
* encephalopathy
230
what is the general function of the gall bladder?
store concentrates and bile
231
what is the composition of bile?
* water
* electrolytes
* organic solutes
* bile acids
* pigment
* cholesterol
* phospholipids
232
what are the primary bile acids?
where are they made?
what is their precursor?
* cholic and chenodeoxycholic acids
* made in the liver
* cholesterol precursor
233
what are the secondary bile acids?
where are they made (via what)?
* deoxyhcolic acid, lithocholic aicd, ursodeoxycholic acid
* made in intestinal tract via microbial metabolism
234
define and describe **cholelithiasis**
formation of gallstones - calculi (solid material) that form in the bile
235
define and describe **cholecystitis**
inflammation of the gallbladder wall and/or cystic duct
236
define and describe **acalculous cholecystitis**
inflammation of the gallbladder wall and/or cytic duct in the absence of stones
237
define **cholangitis**
inflammation usually related to infection of the bile ducts
238
define **choledocholithiasis**
obstruction of the biliary tract by gallstones
239
where can gallstones be present?
bile ducts, gall bladder, cystic duct
240
what do gallstones typically consist of?
cholesterol aggregates and/or calcium
241
describe gallstone formation
* supersaturation of bile with cholesterol causing precipitation
* nucleation of crystals
* hypomotility (stasis of bile) or general movement of anatomy that allows formation
242
pain associated with gallstones typically occurs when?
when stones move throughout the ductal system
243
what are some risk factors for gallstones (3)?
* high cholesterol in bile
* high cholesterol intake
* obesity
244
what is the composition of pigment stones?
pigment polymers and calcium salts
245
describe black pigment stones
* most common
* idiopathic or associated with cirrhosis or hemolysis
* excess bilirubin, rbc degradation, hemolysis
246
describe brown pigment stones
* common is areas with greater risk of parasitic infection
* associated with biliary parasitosis, bacterial colonization, and infection
247
what are some clinical manifestations of gallstones
* asymptomatic
* obstruction of duct by large calculi causing radiating pain
* epigastric pain in upper right abdomen
* nausea and vomiting
* bile back up to liver
* risk of rupture
248
describe chronic cholelithiasis by:
* biliary colic
* manifestations
* diagnosis
* treatment
* biliary colic - intermittment obstruction of cystic duct
* mani: worse with meal, persistent epigastric radiating pain, nausea/vomiting/sweating, increases steadily for 15 min, fatty food intolerance
* diagnosis: ultrasound
* treatment: cholecystectomy, chemical dissolution of stones, lithotripsy (mechanical breaking of stones)
249
describe acute cholecystitis by:
* definition
* clinical manifestations
* diagnosis
* treatment
* definition: acute inflammation of gallbladder wall, obstruction of cystic duct frequently (related to bile stasis)
* manifestations: severe abdominal pain, radiates to back, fever, leukocytosis, mild elevations of bilirubin and serum transaminases
* diagnosis: abdominal ultrasound
* treatment: laparoscopic cholecystectomy, antibiotics
250
describe acaclulous cholecystitis
* occurs in patients without preexisting gallstones
* males >50
* typically occurs in major surgery, critical illness, trauma, burn-related injury, total parenteral nutrition
* rapid development of gangrene, perforation, emphysematous cholecystitis , and empyema
251
describe chronic cholecystitis
* chronic inflammation of gallbladder wall
* low-grade irritation from gallstone, recurrent acute attacks
* predisposing factors: diabetes, obesity
* clinical manifestations: asymptomatic / intermittement biliar colic or acute attacks
* complications; biliary sepsis, porcelain gallbladder, higher risk of cancer
252
provide an overview of the appendix and its functions
* vermiform organ that protrudes from cecum
* right quadrant of abdominal cavity
* function - immunoprotective function, containment of good bacteria
253
what are some causes of appendicitis?
* appendicolith
* fecalith
* tumors that could be benign or malignant
* intestinal parasites
* hypertophied lymphatic tissue
* unknown exact etiology
254
what are some clinical manifestations of appendicitis?
* intrluminal pressure build up
* neutrophil buildup
* lower right quadrant abdominal pain
* localized, sharp, stabbing pain
* fever
* malaise
* urinary frequency/urgency
255
how is appendicitis diagnosed?
* physical exam and clinical presentation
* blood work with elevated leukocytes
* imaging
256
257
how is appendicitis treating?
* surgical removal via appendectomy
* ruptured - irrigation through abdominal cavity
HLTH 341 - Pathobiology
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