-
Name causes of Pancreatitis
- drugs
- genetics
- gallstones/cholecystisis
- vascular disease
- infections
- hypercalcemia
- High lipids/protein
- trauma
- Alcohol
-
Where does pancreatitis usually occur and what gender
- High developed countries
- women
-
What usually causes pancreatitis in men? women?
-
How is cholecystitis caused
gallstones s/c to high cholesterol, billiary calcium and protein which obstructs bile ducts
-
what age is cholecystitis common in, what conditions
- >40
- obesity
- multiple pregnancies
- genetics
- estrogen supplements
- sickle cell
- rapid weight loss
-
what is the disease process of pancreatitis
inappropriate release of pancreatic enzymes which destroy pancreatic tissue and elicit acute inflammatory response
-
what does acinar cells release and how does that play a role in pancreatitis
- typsin
- typsin continues to produce pancreatic enzymes faster than pancreas can eliminate them destroying pancreatic tissue
-
Name 5 inflammatory mediators that play a role in pancreatitis
-
How do inflammatory mediator exacerbation cause further damage in pancreatitis
develops small vessel thromboses and injures acing cells
-
What results after bile duct obstruction in cholecystitis
glycoprotein mucous layer in gallbladder is irritated and opens mucus epithelium to direct detergent action of bile salts
-
What does gallbladder wall release of prostaglandins cause
distention and inc intraluminal pressure that compromises blood flow to mucosa
-
Name 2 primary prostaglandins released from gallbladder wall in cholecystitis
-
What does pancreas look like morphologically in pancreatitis
- edema
- fat necrosis
- paracyhma destruction
- interstitial hemorrhage
-
How does fat necrosis occur in pancreatitis
lipase and fatty acids combine with calcium forming insoluble salts
-
how does cholecystitis appear morphologically
- enlarged and firm
- red/green/black from subserosal hemorrhage
- cloudy/turbid bile with fibrin, pus, and hemorrhage
-
gallbladder that is thick and hyperemic or becomes necrotic is known as
gangrenous cholecystitis
-
s/s of Pancreatitis
- Elevated amylase and lipase
- pancreatic enlargement
- PRIMARY: constant intense abd pain radiating to back and left shoulder with anorexia, n/v
-
Which lab is most sensitive to pancreatitis
lipase
-
What are severe s/s of pancreatitis
- dyspnea (diaphragmatic inflammation)
- Pleural effusion
- ARDS
- Leukocytosis
- DIC
- Edema
- Shock
-
S/s of Cholecystitis
- Murpheys sign
- RUQ pain, fever, leukocytosis
-
What is tenderness and guarding of hypochondriac exacerbated by inspiration
Murpheys sign
-
When does lipase peak
24 hrs
-
What are s/s of Acute attack of cholecystitis
RUQ pain >6 hours w/ tachycardia, diaphoresis, n/v, anorexia, and mild fever
-
When bile duct is obstructed what occurs in the liver
hyperbilirubinemia and pt presents with jaundice
-
What 2 things must be present for pancreatitis to be diagnosed, EITHER
acute onset of severe epigastric pain radiating to back, pancreatitis on imaging, amylase or lipase levels 3x higher than upper normal limit
-
What tx is available for pt not eligible for surgery
- oral dissolution therapy with bile salts
- percutaneous cholecystectomy with stone extraction
- extracorpeal shock wave lithotripsy
-
Whats reoccurrence rate of cholecystitis
50%
-
How is Hep A transmitted
- Fecal oral route
- Contaminated water or food supply (raw or steamed shellfish)
-
Where is HAV common
underdeveloped countries
-
How long is HAV shed in stool
2-3 weeks before and 1 week after onset of jaundice
-
Is there a chronic form of HAV
no, host eliminated
-
How is Hep B spread
- bodily fluids through break in skin or sex
- IV drug abuse
- Mother to fetus
-
What percent does Hep B spread through mother to fetus
90%
-
How long can a pt be contagious for Hep B
life
-
What hepatitis is a precursor for chronic liver disease and hepatocellular carcinoma
Hep B
-
What disease is categorized as scarring of the liver after repeated injury
Cirrhosis
-
How does HAV enter liver
enters blood stream via epithelium of GI and travels to liver
-
Where does HAV virus replicate
in cytoplasm of hepatocytes using hepatocytes own ribosomes
-
What does HAV require in order to replicate itself
initiating factor 4G from undamaged hepatocytes
-
How long does HAV replicate withought an immune response
2-6 weeks
-
What happens after 2-6 weeks when immune system recognizes HAV
cytotoxic T cells and NK cells attack HAV infected hepatocytes destroying infection and it resolves
-
What cellular immunity plays a key role in hepatocellular injury during HAV infection
CD8+ T cells
-
What antibody type appears against HAV with onset of symptoms making it a reliable marker for acute infection
IgM
-
How does HBV enter liver
attaches to receptor called NTCR triggering endocytosis of virus into hepatocyte
-
How long is HBV incubation period
2-26 weeks
-
What immune response is associated with acute resolution of HBV
CD8+ and CD4+ T cells producing interferon-y cells
-
How are hepatocytes injured during HBV
not directly, but from CD8+ cytotoxic T cell attacking infected cells
-
Why is it difficult to cure HBV
due to virus ability to insert itself into host DNA disguising itself so it isn't recognized by immune response
-
What appears before HBV symptom onset
HBaAg
-
When does HBaAg peak in HBV
during overt disease
-
WHen does HBaAg decline in HBV
undetectable in 12 weeks but can persist to 24 weeks
-
What can be detected serologically before anti-HBs antibody is detectable
IgM anti-Hbc antibody
-
What 3 things does persistence of HBeAg indicate in HBV
- Continued viral replication
- infectivity
- probable progression to chronic hepatitis
-
What does appearance of anti-HBe antibody imply
acute infection has peaked and is on the wane
-
Why do nodules develop on parts of the injured liver in Cirrhosis (3 causes)
- Glucagon
- Insulin
- Increased Blood flow
-
How does portal HTN develop in cirrhosis
New blood vessels form but are compressed by nodules causing blood pressure to rise in small vessels which back up to the portal vein
-
When does scarring of liver begin in cirrhosis
WHen hepatic stellate cells convert to myofibroblasts
-
What induces chrinkiage of myofibroblasts resulting in cirrhosis
Endothelin-1
-
What causes necrosis seen in liver failure in Cirrhosis
Liver cells keep duplicating even around dead liver cells
-
How does the liver appear in severe cases of acute viral hepatitis
atrophic and necrotic
-
How does Chronic Viral Heptatis appear in liver through a biopsy
ground-glass hepatocytes
-
What is a biopsy of liver for relating to chronic viral hepatitis
- Grading and staging
- Determine if pt would benefit from antiviral therapy
-
What happens in liver from Cirrhosis s/c to viral hepatitis
liver's regenerating parenchymal nodules become surrounded with dense scar tissue
-
In chronic liver disease and cirrhosis what 2 things play a role in affecting liver function and increases with advancing stages of disease
- Stem cell activation
- Ductular reactions
-
What is the positive aspect of ductular reaction in chronic liver disease and cirrhosis
increases parenchymal regeneration incorporating more stem cells into the turnover rate of hepatocytes in order to produce more viable liver tissue
-
What is the negative aspect of ductular reaction in chronic liver disease and cirrhosis
may stimulate scar tissue formation
-
What biopsy specimens appearance are least likely to be associated with portal HTN s/c to cirrhosis
narrow, densely compacted fibrous septa separated by large islands of intact hepatic parenchyma
-
What biopsy specimen appearance are most likely associated with portal HTN and end stage disease s/c to cirrhosis
BROAD bands of dense scar tissue with DILATED lymphatic spaces with less intervening parenchyma
-
What classification system is used to classify chronic liver disease severity and describe
- Child-Pugh
- Class A- well compensated liver
- Class B- partially compensated liver
- Class C- decompensated liver
-
S/s of Acute Viral Hepatitis
- Jaundice
- Ascites
- Fatigue/lethargy
- Anorexia
- Abdominal Pain
- PRUITIS (SO SEVERE)
-
How is severe pruitis relieved during Acute Viral Hepatitis
liver transplant
-
What percent of individuals are asymptomatic until advanced stages of Acute Viral Hepatitis
40%
-
What Grade does Hepatic Encephalopathy in acute liver failure involve: mild confusion and changes in behavior
Grade 1
-
What grade does hepatic encephalopathy in acute liver failure involve: lethargy and confusion
Grade 2
-
What grade does hepatic encephalopathy in acute liver failure involve: severe lethargy only awoken with stimulation
Grade 3
-
What 4 concerns are involved in later stages of hepatic encephalopathy s/c to acute liver failure
- Increased ICP
- Cerebral edema
- Seizures
- Resp Depression
-
What grade does hepatic encephalopathy in acute liver failure involve: comatose and unresponsive
Grade 4
-
What are lab markers to diagnose liver failure
- Abnorm coags
- INR = to or >1.5
- Prolonged ptt
- >Billi and ammonia
- <ph/electrolytes
- aminotranseferase levels INC (spec HAV)
- ALT > AST
-
How to treat HAV
like the common cold
-
How is hepatic encephalopathy caused
build up of ammonia which is neurotoxic
-
How can hepatic encephalopathy be treated
lactulose
-
How does lactulose help hepatic encephalopathy
binds to ammonia in gut to be pooped out
-
What is infiltrating ductal adenocarcinoma of pancreas known as
pancreatic cancer
-
What age does pancreatic cancer usually affect, gender, and race
-
2 risk factors of pancreatic cancer
- smoking
- chronic high fat intake
-
What percentage is pancreatitis associated with r/t pancreatic cancer
50%
-
Two genetic mutations show inc of pancreatic cancer
- CFTR (cystic fibrosis gene)
- PRSS1 (cationic trypsinogen)
-
Inactivation of what two tumor suppressor genes are inherited with pancreatic cancer
-
what oncogene is believed to be most common and earliest mutation in pancreatic cancer
KRAS
-
What two things are believed to result in development of precursor lesions in pancreatic cancer
- telomere shortening
- activating mutations of KRAS
-
3 types of pancreatic lesions
- Pancreatic intraepithelial neoplasia
- Mucinous cystic neoplasm
- Intraductal papillary mucinous neoplasm
-
Where do most infiltrating adenocarcinomas of pancreas usually occur
Pancreatic head
-
What 3 places does pancreatic cancer mostly infiltrate
- common bile duct
- portal vein
- lymphatic system
-
What is a common occurence of pancreatic cancer related to billary involvement
billiary obstruction
-
What 2 places can pancreatic cancer directly invade
adrenal and spleen
-
What are two most distinctive features of pancreatic malignancy
- Early invasion
- Elicitation of desmoplastic response
-
What is desmoplastic response in pancreatic cancer
neoplastic parenchymal cells and fibroblasts generate and deposit copious amounts of collagenous stroma
-
What can impede diagnosis via biopsy and responsiveness to therapy in pancreatic cancer
Accumulation of fibrotic tissue
-
s/s of pancreatic cancer
- asymptomatic till it invades other organs (vague and nonsepcific)
- pain
- abd discomfort
- pruitis
- jaundice
- wt loss/anorexia
- malaise/weakness
-
First symptom of pancreatic cancer to appear
pain
-
What causes weight loss in pancreatic cancer
fat and protein malabsorption that occurs when obstructed bile duct impairs enzyme secretion and flow to duodenum
-
Less common s/s of pancreatic cancer
- epigastric pain
- backache
- new onset DM
- acute pancreatitis
- N/V
-
3 fatal aspects of pancreatic cancer
- Hepatic failure
- malnutrition
- systemic disease
-
What is the leading cause of preventable pancreatic cancer
smoking
-
What is hepatocellular statosis
fatty change
-
What is steatohepatitis
alcoholic hepatitis
-
What is steatofibrosis
up to and including cirrhosis and later stages of disease
-
Gender and race most common with alcoholic liver disease
-
What is genetic component of alcoholic liver disease and what ethnicity is it common in
individuals with ALDH (detoxifying enzyme) can't tolerate alcohol, asian
-
What are the two most important underlying factors of hepatocarcinogensis
- Viral infections
- Toxic injuries (alflatoxin, alcohol)
-
What causes cholangiocarcinomas
- infestation by liver flukes
- chronic inflammatory disease of large bile ducts
-
How does estrogen play a role in alcoholic liver disease
increases gut permeability to endotoxins expressing kupffer cells in liver to release cytokines
-
What enzyme converts alcohol to acetaldehyde
alcohol dehydrogenase
-
What enzyme converts acetaldehyde to acetate
acetaldehyde dehydrogenase
-
In alcoholic liver disease, what promotes fatty infiltrates of the liver
Alcohol and Acetaldehyde dehydrogenase reduce NAD to NADH inhibiting gluconeogenesis and increases of fatty oxidation
-
How does alcohol cause release of bacterial endotoxins from gut into portal circulation inducing inflammatory responses of liver in alcohol liver disease
Activation of NF-kB and release of TNF, IL-6, and TGF-a
-
How does alcohol lead to decrease in hepatic sinusoidal perfusion
stimulates release of endothelians from sinusoidal endothelial cells causing vasoconstriction, contraction of activate, and myofibroblastic stellate cells
-
In response to hepatic injury what do growth regulators induce
hepatocellular hyperplasia and angiogenesis
-
4 genetic pathways of Hepatocellular carcinoma
- p53
- PICKA
- beta-catenin
- ARID2
-
What things usually cause death in hepatocellular carcinoma
- cachexia
- GI/esophageal variceal bleed
- liver failure with hepatic coma
- rupture of tumor with fatal hemorrhage
-
Activation of what two genes are most common mutational events in hepatocellular carcinoma
-
What is strongly associated with aflatoxin
TUMORS
-
Where do cholangiocarcinomas occur
bile ducts within and outside the liver
-
What extra hepatic tumors are located at the junction or right and left hepatic ducts
Klatskin tumors
-
Morphological characteristics seen in Alcohol liver disease
- fatty liver (yellow and greasy)
- hepatocyte swelling and necrosis
- MALLORY-DENK BODIES
- CHICKEN WIRE FENCE PATTERN
-
When are direct extension of hepatocarcinoma more likely
tumors >3cm in size
-
s/s of alcohol liver disease
- hepatomegaly
- mild elev of bili and alk phos
- nonspecific sx
-
What percent of pt have elev a-fetoprotein in advanced hepatocellular carnicoma
50%
-
What is the morphological difference between alcoholic r/t hepatic staetosis and non-alcohol steatohepatitis
- Nonalcoholic have more mononuclear cells than neutrophils
- Mallory Denk bodies more clear in alcoholic
-
What diarrheal disease is immune mediated
Celiac
-
What infectious enterocolitis disease is caused by troperyma, who does it usually affect
- Whipple disease
- white male farmers or those working with animals and in soil
-
What is the most common parasitic pathogen transferred by food or water, contaminated fecal matter, and outdoor water sources that is a diarrheal disease
Giardia
-
Most common cause of transmission of Giardia
outdoor water sources
-
What disease involves HLA proteins producing components of gluten contained in particle of carbohydrate called gliadin
Celiac
-
Describe patho of celiac
Gluten digested by peptides > peptides express IL-15 > IL-15 proliferate CD8+ lymphocytes > Lymphocytes express NKG2D > NKG2D attacks enterocytes > damages epithelium allowing gliadin peptide to interact with HLA > cytokines produced > atrophy of villi of small intestine
-
What causes lymphatic obstruction in whipple disease
gram+ actinomycete bacteria on macrophages in small intestine
-
What is needed to expel Giardia infection
IgA and IL-6
-
What causes Giardia
flagellated protozoans decrease expression of lactase, damage small intestine and microvillus
-
What is seen morphologically of celiac disease
- Inc CD8
- Villous atrophy
- Inc plasma
- Mast cells
- Eosinophils
-
One of the markers of celiac disease
HIGH INTRATHELIAL LYMPHOCYTE #s
-
What is seen morphologically in Whipple disease
- Macrophage accumulation in lymph, synovial joints, cardiac valves, brain
- Shaggy gross appearance
-
Giardia morphological characteristic
pear shaped with 2 nuclei
-
Hallmark of Celiac Disease
- STEATORRHEA (frothy, greasy stool- large amounts of fat)
- Nutritional def: b12, folate, iron, vit KCD, calc, mag, K+
- Itchy blistering lesion (dermatitis herpetiformis)
-
S/s of Whipple disease
- Joint pain and swelling
- neuro, cardiac, pulmon issues
-
What may be found in stool samples of pts with giardia
cysts
-
What is included in celiac panel
IgA and anti-tissue transgultaminase antibodies
-
How does PCP differientiate between celiac and gluten intolerance
Gene changes
-
What is considered diarrhea
3+ liquid BM a day
-
What is considered acute diarrhea versus chronic
A: 1-2 days-2 weeks
C: Liq BM >2 weeks (seen in Crohns and UC)
-
What are ulcers that result from persistent inflammation and degradation of mucosal protective structures
Peptic ulcer disease
-
Common causes of PUD (90% of cases)
NSAIDS and H Pylori
-
Patho of PUD
more acid produced and less bicarb
-
H pylori patho of PUD
H pylori produces ammonia which protects it from acid, excess ammonia hinders bicard transport allowing inc acid production and also impairs phospholipid mucous layer that protects endothelium
-
NSAID patho of PUD
Interfere with prostaglandin production vital to mucosal protection and hinder nitric oxide and hydrogen which play a role in mucous production, increasing vasculature, and preventing neutrophils from damaging mucosal lining
-
What are prostaglandins made of and why is that important with NSAIDS
Cox-1 and Cox-2 (NSAIDS pevent COX from functioning properly)
-
s/s of PUD
- 70% asymptomatic
- epigastric burning or aching
- hemorrhage or bowel perforation if severe
- dyspepsia (80%)
- upper abd pain
- Extreme cases: hematemesis, black tarry stool
-
Classic sign of PUD
Upper abd pain 2-5 hours after meal or between 11pm-2am when acid secretion is at its highest
-
When is ulcerative colitis usually diagnosed?, gender? ethnicity?
- 15-40 then again at 50-80
- Female
- Jewish
-
Patho of UC
damage to mucosal barrier allows microflora to trigger uncontrolled inflammatory response
-
Production of IL-13 triggers what in UC
more NK T lymphocytes
-
How do T helper 9 cells inhibit mucosal healing in UC
decrease IL-9 in epithelium which incs TNF
-
What is influx of neutrophils into the intestinal glands called
crypts
-
What occurs during cryptitis of UC
goblet cells release more mucus and epithelial cell turnover increases
-
What does chonic cryptitis lead to in UC
crypt abscesses
-
What morphological changes take place in UC
- inflamed mucosal surface from rectum to cecum
- mucosa flattens
- pseudopolyps
-
How do pseudopolyps develop in UC
rapid tissue regeneration
-
What is at the base of each ulcer in UC
increased fibrin, capillaries, and inflammatory cells
-
s/s of UC
- Blood in stool
- Incontinence, urgency, fatigue, inc BM
- STRINGY MUCUS DISCHARGE
- severe (15%) - fever, wt loss
-
Symptom common in Crohns and not UC!
Abd pain
-
What may initial attack of UC require
surgery
-
4 categories of UC
- Proctitis
- Left sided disease
- Subtotal colitis
- Pancolitis
-
What may pts with UC develop as a result of irritation from freq stools
skin tags or anal fissures
-
3 symptoms of UC not involving colon
- peripheral arthritis
- sclerosing cholangitis
- pyoderma gangrenosum
-
What 2 things can protein loss s/c to UC cause
-
How does Crohns Disease present
RLQ pain
-
Morphological characteristic of crohns
- fibrosing strictures
- bowel perforations
- peritoneal abscess
- fistulas
- serpetine ulcers
- thcik appearance of intestinal wall
- SKIP LESIONS OCCUR IN CD
-
What 3 areas of GI does CD typically affect
- terminal ileum
- ileocecal valve
- cecum
-
What is most common form of esophagitis
GERD
-
What percent of patients with dyspepsia develop Barrets esophagus
8.3%
-
What is the most prevalent esophageal cancer
squamous cell carcinoma
-
What is most prevelant cancer associated with Barrets esophagus
adenocarcinoma
-
What is most common cause of gastric reflux
relaxation of lower sphincter
-
WHat causes relaxation of lower sphincter associated with GERD
- gastric distention
- stomach content
- decreased sphincter tone
-
2 steps of evolution of chronic GERD
- Metaplasia from chronic inflammation of squamous transforming to columnar
- Intestinal metaplasia, development of goblet cells or intestinilization of mucosa
-
What can BE lead to (barrets)
Progress to dysplasia then adenocarcinoma called Barret's metaplasia-dysplasia-carcinoma sequence
-
How can BE transform and develop into rapid evolution of adenocarcinoma
inactivation of TP53 causing genome doubling
-
What appears morphologically in advanced stages of GERD and what does that indicate
- Neutrophils and eosinophils
- inc intraepithelial inflammation & tissue destruction
-
When can basal cell hyperplasia be determined in advanced stages of GERD
when basal layer is >15%
-
How does BE look morphologically
salmon colored velvety mucosa
-
-
What type of cells is cardiac mucosa present with in BE
goblet
-
4 categories to describe dysplasia
- None
- Indefinite
- Low grade (loss of surface maturation)
- High grade
-
As adenoma of BE evolves how will it look
- infiltrates
- ulcerations
- masses
- poss obstruction
-
s/s of reflux esophagitis
- bleeding ulcers
- hematemesis
- melena
- heartburn
- chest pain
- hiatal hernia
-
WHat two conditions is common with hiatal hernia
BE and Chronic GERD
-
What percent of BE advace to adenocarcinoma and what is the percent of 5 year survival rate once that occurs
-
First line treatment for reflux esophagitis
Behavior and diet changes
-
What diet should pts with esophageal reflux be on and how should they sleep for comfort
- mediterranian
- HOB elevated
-
What causes genetic metabolic liver disease; Hep B
- Blood
- Birth
- Sex
- Drug needles
-
Patho of Hep B
Virus with round, partially double stranded DNA with nucleotides cause abnormal protein coding and subsequent abnormal hepatocyte funtions
-
What is HBV surface antigen that infects hepatocytes by enveloping glycoproteins and results in overwhelming synthesis of more of that antigen
HBsAg
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