SGU Term 5 BSCE Book 2 Flashcards
Colestyramine
management of cirrhosis
help puritis
4g/8h PO, 1 hr after other drugs
Bacterial Endocarditis
Janeway lesions
Osler nodes
Roth spots
Splinter hemorrhages
Causes of liver cirrhosis
Alcohol Hep B,C,D Hemochromatosis a1 antitrypsin def. Wilson’s disease Autoimmune hepatitis NAFLD Biliary tract disease
Cirrhosis complications
Ascites Spontaneous bacterial peritonitis Gastroesophageal varices Hepatic encephalopathy Hepatorenal syndrome Hepatopulmonary syndrome Hepatocellular carcinoma
Palmar erythema
Increased estrogen bc cirrhosis
Decreased ammonia metabolism in cirrhosis
Hepatic encephalopathy
compensated cirrhosis
Calculate MELD every 6 mo
MELD >12
High risk of complications of cirrhosis
MELD score
3.78 x log serum bilirubin + 11.2 x log INR + 9.57 x log serum creatinine + 6.43
Pt has been dialyzed twice in last week
Serum creatinine 4 in MELD score
Child Tircotte Pugh Classification of Cirrhosis
A = 5 to 6 B = 7 to 9 C = 10 to 15
Ascites management
Spironactone 100 mg/day increase dose every 2 days to 400 mg/day
Should have daily weight loss of .5 kg
If not, add furosemide 120 mg/day
Do U&E, Cr often
Ascites fluid restriction
1.5 L per day
Ascites low salt intake recommended
40-100 mmol/day
Therapeutic paracentesis for ascites
Concomitant albumin transfusion 6-8g/L removed
Refractory ascites
Trans jugular intrahepatic portosystemic shunt
Cirrhosis + ascites of 15g/L protein or less
Prophylactic oral ciprofloxacin or norfloxacin, until ascites resolves
Spontaneous bacterial peritonitis
Presenting w fever usually
WCC 250mm3 in ascitic fluid or more
Bacterial peritonitis empiric treatment
Cefotaxime (claforan) and ceftriaxone (rocephin)
Bacterial peritonitis prophylaxis
Ciprofloxacin 250mg PO daily
OR
CoTrimoxazole 960 mg weekdays only
Cirrhosis, esophageal varices screening
Endoscopy every 3 years
Cirrhosis + medium or large esophageal varices
Endoscopic variceal band ligation
Cirrhosis + upper GI bleeding
Prophylactic IV Abx and vasoactive drugs
Cirrhosis or significant fibrosis
METAVIR stage > or equal to F2
Ishak stage > or equal to 3
Surveillance every 6 mo for HCC by: hepatic ultrasound, alpha fetoprotein testing
no significant fibrosis or cirrhosis METAVIR < F2 Ishak < 3 Older than 40 Family Hx of HCC HBV DNA > or equal to 20,000
Surveillance every 6 mo
no significant fibrosis or cirrhosis METAVIR < F2 Ishak < 3 Younger than 40 HBV DNA < 20,000
No surveillance
Early Hep C
Arthralgia Paresthesia Myalgia Pruritis Sicca Sensory neuropathy
Late Hep C
Hepatic encephalopathy Ascites Hematemesis or melena Palmar erythema Dupuytren contracture Asterixis Leukonychia Clubbing Icteric sclera Temporal muscle wasting Enlarged parotid Cyanosis Fetor hepaticus Gynecomastia Testicular atrophy Paraumbilical hernia Caput medusae Hepatosplenomegaly Abdominal bruit Scant body hair Spider nevi Petechiae Excoriations
Sustained eradication of HCV
Absence of HCV RNA in serum 12 weeks post antiviral treatment
Antiviral treatment for Hep C?
High ALT > 18y/o \+ HCV antibody and serum HCV RNA compensated Hb at least 12 for women 13 for men, neutrophil > 1500, creatinine <1.5
Hep C treatment
Oral PI (boceprevir BOC or telaprevir TVR) Pegaylated IFN (PegIFN) Ribavirin RBV
Alcohol cirrhosis risk
7-13 drinks/week women
14-27 drinks/week men
Alcoholic fatty liver
AST/ALT >2
High GGT
Maddrey Discriminate function
Bilirubin + 4.6 x prothrombin time -control
High if alcoholic hepatitis has poor prognosis
> 32: 50% mortality w/in 2 mo of onset of alcoholic hepatitis
DF>32
Corticosteroids
DF<32
Pentoxifylline
DF<32
MELD<21
Glasgow<9
Supportive care
DF>32
MELD>21
Glasgow>9
Prednisolone 40mg/day
(Or pentoxyfylline 400mg 3x per day)
Lillie score at one week
<0.45 continue prednisolone 28 days
>0.45 stop prednisolone
Upper GI bleed
Peptic ulcer
Mallory weiss tears
Esophageal varices
Esophagitis
Glasgow Blatchford Score
0: low risk
>8: ICU admission
Glasgow score of 0
Hb>12.9 men or 11.9 women Systolic BP >109 Pulse <100 BUN <39 No melena or syncope No liver disease or heart failure ever
Upper GI bleed
Blood transfusion at 70-80 g/L Hb, higher threshhold of severe bleeding w hypotension
Upper GI bleed + glasgow <1
Outpatient endoscopy
Upper GI bleed treatment
Erythromycin (prokinetic agent) and PPI
Endoscopic therapy
Injection therapy (epi, always followed by second modality) Thermal probes (bipolar electrocoagulation, heater probe) Clips
Recurrent bleeding
Repeat endoscopic therapy
Subsequent bleeding
Trans arterial embolization
Surgery
Esophageal variceal bleeding
Ligation
Gastric varices
Injection of tissue adhesive
Massive refractory esophageal variceal bleeding
Removable covered metal stent is preferred to balloon tamponade as temporizing measure
Ulcers w high risk lesions post endoscopy
High dose PPI for 72 h
Post endoscopy, pts with cirrhosis
Continue Abx for a week regardless of bleeding source
Post endoscopic Variceal bleeding
Vasoactive drugs for 5 days
Following hemostasis post endoscopy
Reintroduce aspirin/antithrombotics
External hemorrhoids
Minimally invasive:
Rubber band ligation
Sclerotherapy
Coagulation
Hemorrhoidectomy
Hemorrhoid stapling
Colon cancer clinical presentation
Iron deficiency anemia
Rectal bleeding
Abdominal pain
Intestinal obstruction/perforation
Early disease: nonspecific
Advanced disease: abdominal tenderness, macroscopic rectal bleeding, palpable abdominal mass, hepatomegaly, ascites
Colon cancer marker
Serum carcinoembryonic antigen
Colon cancer in cecum and right colon
Right hemicolectomy
Colon cancer in proximal or middle transverse colon
Extended right hemicolectomy
Colon cancer in splenic flexure and left colon
Left hemicolectomy
Colon cancer in sigmoid colon
Sigmoid colectomy
For pts with HNPCC, FAP, metachronous cancers in separate colon segments, acute malignant colon obstructions w unknown status of proximal bowel
Total abdominal colectomy w ileorectal anastomosis
Chemo for colon cancer
5-FU w leucovorin or capecitabine (either alone or w oxaliplatin)
Non surgical colon cancer options
Cryotherapy
Radiofrequency ablation
Hepatic arterial infusion of chemo agents
Diverticulitis etiology
Perforation of diverticula causing extracolonic inflammation
Clinical diverticulitis
Abrupt onset
LLQ pain/tenderness
Low fever
Constipation
Peritonitis caused by perforation
Rebound tenderness and abdominal rigidity
Diverticular abscess causing bowel obstruction
Diffuse abdominal pain
Abdominal distention
High fever
Diverticulitis I
Symptomatic uncomplicated
Fever, abdominal pain
Colonoscopy or enema to rule out neoplasms and colitis
Diverticulitis II
Recurrent symptomatic
CT or barium enema
Diverticulitis III
Complicated
(Abscess, hemorrhage, stricture, fistula, peritonitis, obstruction, etc)
CT
Uncomplicated diverticulitis
Abx
Conplicated diverticulitis
ACS hinchey Ib or II
Abx plus percutaneous drainage for large abscess, small one just Abx
Conplicated diverticulitis
ACD hinchey III or IV
Emergency surgery
Ib
Pericolic or mesenteric abscess
II
Large abscess extending into pelvis (walled off)
III
Gaseous release
IV
Fecal discharge
Drugs to avoid in diverticulitis
Nonsteroidal nonaspirin anti inflammatories
Resolution of acute diverticulitis (high quality exam not done in past 6 mo)
Colonoscopy
Colon cancer nutritional eval
Vit B12
Iron
RBC folate
Marker of intestinal inflammation
Fecal calprotectin
Enzyme check before initiation of therapy w mercaptopurine and azathioprine
TPMT thiopurine methyltransferase
If low, leukopenia, sepsis
pANCA
Ulcerative colitis
ASCA Anti saccharomyces cerevisiae antibodies
Crohn disease
Diagnose crohn’s using
Ultrasonography
Determine extent and severity of colitis
Colonoscopy
Flexible sigmoidoscopy
Crohns location
Entire GI tract
Mostly transition from small to large intestine
Ulcerative colitis location
Colon
Crohns etiology
Skip lesions
Increased risk of cancer
UC etiology
Uniform from rectum up to colon
Marked cancer risk
UC stmptoms
Bleeding
Crohns symptoms
Toxic megacolon
Perf of colon
UC extraintestinal
Liver disease
Crohns extraintestinal
Fistulas
Abscesses
Crohns histology
Granulomas
Lymphocytic
String sign on x ray
UC histology
Neutrophilic
Lead pipe colon on x ray
UC endoscopy
Crypts, continuous lesions, residual tissue
Crohns endoscopy
Discontinuous lesions, strictures, linear ulcerations
IBD diet
B12, D, iron
IBD meds
Aminosalicylates/metronidazole or ciprofloxacin
Steroids (oral prednisone at 10-40 mg/day tapered once symptom relief)
If steroids cant be tapered without recurrence, use immunomodulators or anti TNF therapy
TNF monoclonal antibody therapies
Immunomodulator azathioprine
Achalasia
Myenteric plexus degeneration
Nitric oxide neurons (inhibition)
VIP neurons
Achalasia due to malignancy secondary to
Pancreatic cancer
Prostatic cancer
Lymphoma
Achalasia due to diseases
Amyloidosis
MEN
glucocorticoid deficiency syndrome
Chagas disease may cause
Achalasia
Achalasia left untreated
Increased risk of squamous cell carcinoma after 50
Achalasia meds (not very useful)
Nitrates
Ca channel blocker
Viagra
Achalasia treatments
Pneumatic balloon dilation
Surgical myotomy
Endoscopic myotomy
Botox injection
Achalasia on x ray
Bird’s beak
Scleroderma stages
Neuropathy
Myopathy
Fibrosis
Consequence of severe GERD
Scleroderma
Scleroderma and GERD
Complicated by decreased saliva production
Decreased gastric emptying
Non cardiac chest pain
Nutcracker
DES
Diffuse esophageal spasm
Simultaneous prolonged contractions
Intermittent dysphagia
Atypical chest pain
(Ca channel blockers, nitrates)
Nutcracker esophagus
High amplitude peristaltic contractions
Odynophagia
Boerhaave syndrome
Transmural distal esophageal rupture due to retching
Surgical Emergency
Plummer vinson syndrome
Dysphagia (esophageal webs)
Iron deficiency
Glossitis
In ELDERLY FEMALE
Eosinophilic esophagitis
Atopy in childhood
Children>men>women
Like GERD but doesn’t respond tk gerd tx
PPI responsive EoE do not have gerd
Omeprazole blocks IL13 induced Eotaxin-3 secretion
EoE path
> 15 eos/hpf
High TGFB1
Subepithelial fibrosis/stenosis
Mucosal fragility
Rings/furrows/exudates/strictures
Cowdry Type A inclusion bodies
HSV esophagitis
Decreased LES
Drugs Alcohol Chocolate Peppermint Fatty foods Smoking
Hypersalivation
GERD symptom
Barrett’s esophagus
Metaplastic process
Squamous to columnar epithelium w goblet cells
Progresses to adenocarcinoma
Esophageal impedance
Measures reflux
GERD med adjustment
Discontinue aggravating meds (anticholinergics)
Therapy:
H2 antagonists
PPI
Fundoplication
Surgery for GERD
Adenocarcinoma
Most common in US
lower 1/3
Squamous cell carcinoma
Most common in world
Upper 2/3
Alcohol and smoking
Secondary esophageal cancer
Extrinsic: lung
Submucosal: breast w pseudoachalasia
Cases entering population
Incidence
Current cases
Prevalence
Cases leaving population
Recovery, death, migration
Type 1 and 2 error
1: false pos
2: false neg
Variance
(Xi - mean)^2 / n-1
St deviation
Square root of variance
Positively skewed
Peak happens earlier
Interval variables
Temp in C or F
Exam score
Plus or minus 1 standard deviation
68%
R^2
Determination
Percentage of variance of y explained by x
Regression
Units of outcome
Lead time bias
Earlier detection by screening so longer survival
Length time bias
Excess of asymptomatic cases detected, while fast progressing only detected after symptoms
Deceleration of gastric motility
Pylorostenosis
Hypokalemia
Diabetes
Peptic ulcer
Parietal cell
HCl
Intrinsic factor - B12 absorption
Chief cell
Pepsinogen - protein digestion
Surface mucous cells
Mucus, bucarbonate
Trefoil factors
For protectiob
ECL cells
Histamine - regulation
G cells
Gastrin - secretion
Nerves
Gastrin-releasing peptide - regulation
ACh - regulation
D cells
Somatostatin - regulation
Achylia gastrica
No HCl
No enzymes
Long term increase of stomach secretion
Proteinases Hyperacidity Peptic ulcer Liver disease Hypercalcemia
Decreased stomach secretions
Achlorhydria
Achylia
Atrophic gastritis
Infectious gastritis
Decrease acid production in most people
Atrophic gastritis
Chronic
Type A gastritis
Autoimmune
Corpus affected
Pernicious anemia (B 12 def)
Megaloblastic anemia
Type B gastritis
H pylori Corpus affected Gastric cancer phenotype Or Duodenal ulcer phenotype - Antral infection
Causes of gastritis
Crohns Sarcoidosis Syphilis Atrophic (Type A and B) Infectious NSAIDs
Curlings ulcer
Dec plasma volume
Burns
Cushings ulcer
Inc vagal stimulation
High ACh
High H+
Head injury
Gastritis vs ulcer
Gastritis - mucosa
Ulcer - muscularis/submucosa involvement
Chronic atrophic gastritis
Inflammatory cell infiltrate
Atrophy of mastric mucosa
Risk of adenocarcinoma
H pylori
Gram neg Spiral Microaerophilic Motile UREASE
Associated: gastritis, ulcer, adenocarcinoma, MALToma, non-ulcer dyspepsia
Chronic H pylori
Duodenal ulcer - high gastrin and acid, protection from gastric cancer
Simple gastritis - majority, high gastrin, normal acid
Gastric cancer - very rare, corpus, multifocal atrophic gastritis, high gastrin, low chloride, low pepsinogen
H pylori culture
100% specific
Affected by PPI
UBT
Most Sensitive
Serology
Sensitive
Not useful after eradication therapy
COX 1
GI mucosal integrity
Peptic ulcer disease pathophys
Increased vagal activity
Parietal cell hyperplasia
More acid
Alcohol diet and caffeine cause
Gastritis
NOT peptic ulcer
Gastric ulcer causes
Impaired mucosal defense
Motility defects (bile backs up and messes with mucous barrier)
Delayed gastric emptying
Mucosal ischemia
Weight loss is seen in
Only in gastric ulcer
Gastric ulcer
Duodenal ulcer
Gastric - aggravated by meals
Duodenal - relieved by meals then recurs a couple hours later
Gastric ulcer bleeding
Lesser curvature bleeds from left gastric artery
Gastric cancer after
Gastric ulcer
Men w Blood group o inc risk of
Duodenal ulcer (into submucosa)
Rapid gastric emptying causes
Duodenal ulcer
Zollinger ellison associated w
Duodenal ulcers most common
tumor of G cells in langerhans islets of pancreas (can also come from duodenum)
Secretory diarrhea
Posterior surface bleed
Gastroduodenal art
H pylori
Duodenal ulcer
High gastrin
Duodenal perforation
Ant > post
Bleeding va perf
Bleeding more in post wall
Perf more in ant wall
Duodenal perf leads to
Air under diaphragm on x ray Peritonitis Pancreatic pain Hypovolemic shock OBSTRUCTION
Diagnosis of duodenal ulcer
Stool antigen test
UBT
serology (active infx)
Antral biopsy w urease test (endoscopic)
Refractory ulcer
Zollinger ellison syndrome
Cancer
Crohn’s
Lymphoma
Hyperglycemia
Acute gastroparesis
Antral hypomotility
Scleroderma, vagotomy, hypothyroidism
Chronic gastroparesis
Motility disorders more in
Female
Diabetic gastroparesis
Autonomic neuropathy
Reduced relaxation
Inc pyloric pressure
Gastroparesis sympt
Bloating N/v Anorexia Dehydration Not much pain
Dumping syndrome
Hyperosmolarc cholesterol rich
Early or late (hypoglycemia)
Postvagotomy diarrhea
Billroth ii surgery (stomach wall removed) - iron and calcium malabsorption
Infx leading to gastric cancer
EB virus
H pylori
Gastric cancer genetics
Germline mutation cdh1 (e-cadherin)
Predysposing syndrome for gastric cancer
Pernicious anemia (autoimmune atrophic gastritis)
Hypertrophic gastropathy leads to
Gastric cancer
Menetrier disease
Gastric hypertrophy Protein loss Parietal cell atrophy Inc mucous cells Stomach looks like brain Precancerous
Chronic gastritis leads to
Antral gastritis or
Multifocal atrophic gastritis -> adenocarcinoma
Acanthosis nigricans
Adenocarcinoma due to hp, early mets to liver and LN’s
Ulcer w raised margins
Intestinal type adenocarcinoma
Lesser curvature
Signet ring cells
Linitis plastica
Diffuse type adenocarcinoma
NO hp
Gastric lymphoma
Secondary to hp - MALToma
Symptoms of stomach cancer
Virchow nodes - left supraclavicular node
Krukenberg tumor - bilateral ovaries, signet ring cells, mucous
Sister mary joseph nodule - subcutaneous periumbilical mets
Interstitial cells of Cajal
GI stromal tumor
Mesenchymal tumor
Leiyomyoma sarcoma
Smooth muscle tumor
GIST
Acute diarrhea
Metabolic acidosis
Chronic diarrhea
Ca and P balance disturbance
Steatorrhea
Bleeding
Osmotic gap
<50 secretory
>125 osmotic
Cholera
Over secretion of Cl
Na and water follow
Night and day
Fasting doesnt help
Vibrio cholera
Gram neg Oxidase pos Curved Flagellated rod Shooting star motility Rice water stool
Increase cAMP in intestinal mucosa
Increased Cl secretion
Cholera risk inc w
PPI
grows on highly alkaline media
ETEC
Heat labile toxin LT - inc camp
Heat stable toxin ST
Pili attach intestinal epithelial cells
Cholera toxin
Activates Gs
Osmotic diarrhea
Laxatives Lactose intolerance High fructose corn syrup Sorbitol Antibiotic related
Infx gastroenteritis
Norovirus - most common
Rotavirus - child
Usually viral, usually self limited
Severe diarrhea and pregnant
Listeria
Sympt w in 6 hours diarrhea
Preformed toxin Staph aureus (mayo) Bacillus cereus (rice)
8-16 hours diarrhea
C perfringes - reheated meat, gas gangrene (lecithinase)
Lecithinase
Splits phospholipids
C perf
After 16 hours
Viral
ETEC or EHEC
Bloody diarrhea
EHEC Campylobacter jejuni Yersinia enterocolitica Shigella Salmonella
EHEC
Shiga toxin (verotoxin)
O157:H7
Hemolytic uremic syndrome (HUS)
Undercooked ground beef
C jejuni
Children
Domestic animal exposure
Precedes guillan barre and reactive arthritis
Yersinia
Puppies
Mimics crohn disease
Shigella
Preschool outbreak
No HS on TSI agar
Salmonella
Undercooked poultry, eggs, produce
Kids playing with pet reptiles
HS on TSI agar
Shiga toxin vs Shiga like toxin
SLT does not cause host cell invasion
Shiga invades intestinal mucosa
Small inoculum 50-100 cells
Shiga toxin
Stops 60s ribosome
Blocks trna binding
Pediatric renal failure
HUS
bc cytokine release
HUS
Microangiopathic hemolytic anemia MAHA
Thrombocytopenia
Renal failure
Schistocytes
Salmonella typhi
Gram neg rod Facultative anaerobe Fecal oral Flagella HS ENCAPSULATED Vi antigen - asplenics!
Rose spots on chest
Sickle cell and osteomyelitis
Campylobacter
Gram neg Comma shaped Corkscrew motility 42 C Precedes guillan barre
Rotavirus
Infant
Dehydration and death
Cryptosporidium
Acid fast oocytes
In water
AIDS
Giardia
Camping/hiking
Foul smelling
Fatty diarrhea
Smiley face trophozoites
Entamoeba
Bloody diarrhea
Liver abscess
Anchovy paste exudate
C dif
Toxin A - brush border, inflamm and fluid secretion
Toxin B - cytotoxic, pseudomembrane
PPI inc risk Gram pos Spore forming Toxic megacolon Fecal transplant
Inflamm diarrhea can lead to
Obstruction
Pancreatic cholera
Non beta islet cell tumor
VIP
multiple endocrine tumors
Chronic diarrhea - secretory
Carcinoid syndrome
5-hydroxytryptophan Histamine Paroxysmal flushing, explosive diarrhea, tachycardia, low BP ELEVATED URINE 5-HIAA Chronic diarrhea - secretory
Limited ileal resection
<100 cm
malabsorbed bile in colon causes secretion
Rx - cholestyramine
Extensive ileal resection
>100 cm Impaired enterohepatic circulation Impaired micelles Fat malabsorption and secretion Rx - low fat diet, medium chain triglycerides
Uncontrolled diabetes
Constipation
Osmotic gap
290 - 2(Na + K) stool
50-125 mixed diarrhea
Stool fat > 14g/100g stool
Malabsorption
Pancreatic insufficiency
Bacterial overgrowth
Stool fat <14
Lactose intolerance (genetic or old)
Laxatives
Sugars
Normal stool weight
<300g/day
Normal osmotic gap or <50
Normal stool fat
Increased wt >300
> 1000 secretory diarrhea
Laxative abuse
Hematochezia
Bleeding from rectum, red
Stable
<500 cc
Orthostatic inc HR
500-700 cc
Orthostatic dec BP
700-1000 cc
Resting inc HR
20% or >1L
Resting dec BP
30-40%
Death
> 50%
When to transfuse
High risk: HCT <27% Hb <9
Variceal bleeding: <21% Hb <7
Melenic stool
200 cc blood
BUN/Cr >35
UGIB
Clean based ulcers
Almost no serious recurrent bleeding
Can go home
Vasoactive meds for esophageal varices
Octreotide
Somatostatin
Vapreotide
Terlipressin
For 2-5 days
Long term meds for esophageal varices
Nonselective Beta blockers + endoscopic ligation
Dont use barium x rays for
GI bleeding
Acute acid suppression in UGIB bc
Platelets aggregate poorly at pH < 6
Inhibit pepsinogen
Small intestine bleeding in kids
Meckel’s diverticulum
Eval small intestine bleeding
Angio
Second look procedure
Capsule endoscopy to look at whole small intestine
Pts with small bowel narrowing
Use CT enterography instead of capsule endoscopy
Small intestine bleed meds
Hormonal tx: orthonovum 1/50 BID
LGIB in kids
IBD or juvenile polyps
Positive fecal occult blood
Colonoscopy
Upper endoscopy if upper symptoms
If iron deficiency do both
D-xylose
Differentiate btw malabsorption from small intestine vs pancreatic insufficiency
Celiac diseased
Diarrhea chylosa Consumption of bowels Small bowel disorder Mucosal inflammation Villous atrophy Crypt hyperplasia
Chances of getting celiac
1 first degree = 10%
2 first degree = 25%
1 second degree = 8%
Identical twins = 70%
Celiac disease genetics
Genetic predisposition
HLA-DQ2 and/or DQ8 + other
Celiac trigger
Virus or bacteria allow gliadin to pass to lamina propria
Adenovirus type 12 sensitizes T cells to gliadin
TTG deaminates glutamine at 4,6,7 on gliadin
Inc T cell response
Celiac serology
Anti-deamidated gliadin peptide (DGP) IgA, IgG
DO NOT USE antigliadin IgA, IgG
Antiendomysial IgA (EMA)
ANTI-tissue transglutaminase IgA (TTG IgA)
Celiac symptoms
Diarrhea Overweight/obese - 32% Bruising, skin rash Dermatitis herpetiformis Iron deficiency anemia Bone pain Ascites Epilepsy Infertility Short stature
Extraintestinal celiac
Liver disease - elevated transaminases, autoimmune hepatitis, primary biliary corrhosis
Ascites
Weight loss
Anemia (iron/folate def)
Bruising - vit k def, elevated prothrombin time
Celiac path
Small intestine Villi blunted Crypts elongated Inflammatory infiltrate Mucosal cracks
Celiac treatment
Gluten free diet plus
Take glutenases
Tight junction modulator: larazotide .5 mg TID
Antiinflammatory
Non-celiac gluten sensitivity
IBS-like symptoms
More common than celiac
No evidence of celiac or wheat allergy
More symptoms than celiac
Wheat allergy
IgE mediated
Itching
Swelling of lips, tongue
Tropical sprue
Persistent Contamination of mucosa by: klebsiella, enterobacter cloacae, e coli)
Toxins make structurally abnormal mucosa
Tropical sprue symptoms
Megaloblastic anemia (folate def)
Watery diarrhea
Abdominal cramps
Flatulence
Tropical sprue treatment
Tetracycline and folate for 6 mo
Bacterial overgrowth dx
Small bowel barium x ray
13c-xylose breath test
Lactulose hydrogen breath test
Whipple’s disease
Tropheryma whipplei - gram pos bacilli
Small bowel, CNS, heart, kidneys, joints
Edema
PAS pos granules in macrophages on biopsy
Whipple’s disease tx
Ceftriaxone then bactrium
IBD smoking
Causes crohn’s
Prevents UC
Appendectomy IBD
Protective in UC
Abx use in first year of life: risk factor for
IBD
IBD breastfeeding
Protective
Omegas in IBD
High omega 6, low omega 3: inc risk
Vit D IBD
Protective
IBD: regulation of secretory activity
XBP1
ORMDL3
OCTN
IBD: innate immunity and autophagy
NOD2
ATG16L1
IRGM
JAK2
STAT3
C13orf31
IBD: regulation of adaptive immunity
IL23R
IL12B
IL10
PTPN2
IBD: development and resolution of inflammation
MST1
CCR6
TNAAIP3
PTGER4
Fibrostenosing CD
NOD polymorphisms
Fistulizing CD
ATG16L1
Loss of haustrations
No granuloma
Limited to mucosa and submucosa
UC
Granuloma formation
Transmural
Rectum spaired
Crohns
Ilieocolitis mimics appendicitis
Crohns
Crohn’s
Oxalate kidney stones bc Ca bound by fat, so Na binds oxalate and is absorbed
Primary sclerosing cholangitis
UC
Gallstones
CD
Pyoderma gangrenosum
UC
Sweet’s syndrome
Map like red lesion
High neutrophils
Extraintestinal for IBD
Episcleritis
CD
Aphthous ulcers
CD
AA, hispanic, asian
Ileocolonic CD
pancolonic UC
East asians
Perianal disease
African American
Joint and ocular involvement
Hispanic
Dermatologic manifestations
Endoscopy in crohns
Cobblestoning
Serpiginous ulcers
Aphthous ulcers
IBD treatment
5-ASA (mesalamine) - remission
Anti inflammatory
Azathioprine, 6-mercaptopurine, methotrexate, tacrolimus
anti TNF (infliximab, adalimumab)
anti integrins (natalizumab, vedolizumab)
Rome IV diagnostic criteria
For IBS
Symptom onset 6 mo ago
Criteria fulfilled for last 3 mo
Abdominal pain 1 day/week in 3 mo + 2:
Defacation
Frequency of stool
Appearance of stool
Prolonged fasting
Improves diarrhea in IBS
IBS pathophys
Mid cingulate cortex - more pain
More motility
Inc IL-6,IL1ß, TNF and TRPV1 -> visceral hypersensitivity, permeability
Inc EC cells, TPH1 polymorphism -> inc serotonin -> inc motility
Visceral hypersensitivity in IBS
Afferent disfunction
Hydrophilic colloid, psyllium
Stool bulling agents for IBS
Anti depressants for IBS
TCA’s - delay gut transit time, visceral afferent neural function changed
Post infectious IBS
Campylobacter
Shigella
Salmonella
Good bacteria in low levels in IBS
Bifidobacterium
Lactobacillus
True diverticulum
Ex. Meckel’s
Herniation of entire bowel wall
False diverticulum
Mucosa and submucosa thru muscularis propria
Diverticula more common in
Left colon
Sigmoid
(Rectum spared)
Diverticula in Asians
70% in right colon and cecum
Diverticula pathophys
Nutrient artery (vasa recti) penetrates muscularis propria
Vasa recti compressed or eroded -> bleeding or perf
High press in sigmoid colon -> high amp contractions -> chronic inflamm -> neuron degeneration -> dysmotility and high intraluminal pressures
High fat stool
Diverticulosis
Hematochezia
Or
Asymptomatic
Diverticulitis
Symptomatic uncomplicated diverticular disease (SUDD)
fever
Anorexia
LLQ pain
Obstipation
Complicated: perf, abscess, stricture
Abdominal distension + localized peritonitis
Pericolonic abscess
Diverticulitis Tx
Bowel rest
3rd gen cephalosporin
Cipro + metro
Amp added for non responders
Most colorectal cancers arise from
Adenomatous polyps
Sessile, serrated polyps
Invasive cancer
Villous adenoma
Mostly sessile
Malignant 3x more than tubular
Colorectal cancer pathophys
Microsatellite/chromosomal instability
APC inactivation or b catenin activation
KRAS or BRAF activation
SMAD4 or TGFbII inactivation
TP53 inactivation
Polyposis coli
5q deletion
Absence of tumor suppressors
1000s of adenomatous polyps, cancer by 40
MYH associated polyposis
MUT4H mutation
Polyposis coli or colorectal CA w/out polyposis
Hereditary nonpolyposis colon CA
Lynch’s syndrome
hMSH2 or hMLH1 mutations
Errors in DNA replication
Proximal/ascending colon by 50
IBD and colorectal CA?
UC>CD
Endocarditis from Strep Bovis
Higher risk of colorectal CA
Tobacco use >35y
Higher risk of colorectal CA
Colorectal cancer - cecum
Tumor may be large w/out obstructive sympt bc stool is liquid here
Colorectal CA - right colon
Ulcerate
Hypochromic microcytic anemia
Fatigue
Palpitations
Colorectal CA - transverse and descending colon
Obstruction
Abd cramping
“Apple core” lesion
Colorectal CA - rectosigmoid
Hematochezia
Tenesmus
Narrowed stool
Colorectal CA screening
Flexible sigmoidoscopy every 5 y after 50
Colonoscopy every 10 y after 50
Descending colon colorectal CA
Apple core
Napkin ring
Sigmoid colon CA
U shape
Lab tests for colorectal CA
Liver function (most common for mets) Plasma CEA
Post op colon CA
CEA every 3 mo
PE every 6 mo for 5 yr
Endoscopy every 3 yr
Rectal cancer
Recurrence of 25% so give post op radiation therapy
Primary prevention of colorectal CA
Aspirin and NSAIDs
Suppress proliferation by inhibiting prostaglandin synthesis
Acute liver failure
In a previously healthy person
Coagulopathy (PT>20 or 4-6 sec longer, INR>1.5)
Encephalopathy
Fulminant liver failure
Encephalopathy w/in 2 weeks
Subfulminant liver failure
W/in 3 mo
Hyperacute LF
Acetaminophen toxicity Acute Hep A or E Jaundice -> encephalopathy <1 week Severe coagulopathy Moderate intracranial HTN
Acute LF
Hep B
Jaundice -> encephalopathy 1-4 weeks
Moderately severe coagulopathy
Mild to moderate intracranial HTN
Subacute LF
Nonacetaminophen drug toxicity SEVERE JAUNDICE Jaundice -> encephalopathy 4-12 weeks Mild coagulopathy Absent or mild intracranial HTN
Viral Hepatitis
PAMPs
Innate immune mediated response leading to ALF
Toxin mediated liver injury
DAMPs
Innate immune mediated response
Leading to ALF
Acetaminophen liver damage
Causes necrosis of hepatocytes
Metabolism of acetaminophen
Some acetaminophen -> NAPQI (cyp450 2E1)
NAPQI needs glutathione to flush it out as cysteine and mercapturic acid
Not enough glutathione? Liver cell damage (covalently binds proteins, oxidative damage and mitochondrial dysfunction)
Acetaminophen toxicity antidote
N acetylcysteine
Precursor of glutathione
NAPQI excretion?
Renally excreted
NAPQI hepatocellular damage
Necrosis in centrilobular (zone III) region bc greater production of NAPQI here
Liver biopsy indicated
Lymphoma
Wilson’s
Lab findings in ALF
Decreased platelets
Hypoglycemia
AST of 3500 units/L
Acetaminophen hepatotoxicity
Alcoholic liver injury fibrosis
Stellate cells
Wilson’s
Hepatolenticular degeneration Autosomal recessive Copper Mutation in ATP7B (chr 13q) Late childhood onset Acute hepatitis -> cirrhosis
Wilson disease pathophys
Defective copper transporting P-type ATPase bc of ATP7B mutation
Most common: histidine to glutamine H1069Q
Copper doesnt get into bile for excretion
Copper not incorporated into apo-ceruloplasmin to form ceruloplasmin (binds Cu in blood)
Free radicals, oxidation of lipids and proteins
Non toxic Cu storage
Metallothionein
Kayser fleischer
Cu in descemet membrane in limbus of cornea
Electron dense granules rich in copper and sulfur
Also seen in chronic cholestatic disorders - primary biliary cirrhosis
Wilson’s kidneys
Renal disease bc proximal tubule damage leading to Fanconi syndrome
Hemolytic anemia in wilsons
Oxidative injury by Cu
Lab findings in wilsons
Decreased total serum copper
Decreased serum ceruloplasmin (early stage)
Increased cerum and urine free copper (late stage)
Diagnosing wilsons
Low ceruloplasmin <50
Urinary Cu >100/day
In hepatic tissue >250