HY GI and Liver Path

As the Step 1 exam approaches for many of you, I give you all the credit. Did you know, you are one of 2% of the population that wants to go to medical school! Not only that, you did it! You have learned more in two years than an undergrad learns in 4!

Testing Strategy: Thinking globally/big picture, integrating material, making assertions, problem solving and reading comprehension will make these numbers take flight!

30% of the Test is Knowledge/recall. If you are working daily to put information in and paid attention in the 1st two years, you should be able to get 90% of this part of the exam. = ~27%

70% of THE test is problem solving/interpretation/integration of information. If you can just get to guessing ~ 50%, = ~ 35% of the this portion correct. That puts you at 62% of all your questions correct. That is the national mean for Step 1!

GI

Integrated Info
Men more likely to have
- Barrett esophagus
- Esophageal cancer ( Iran, china)
- Pyloric stenosis (newborns)
- Peptic ulcers
- Hirschprung's disease
Causes of hematemesis
- lacerations
- varicosities
- acute gastritis
- peptic ulcer
- Zollinger-Ellinson syndrome (lots of peptic ulcers)

Malignant Tumors with Bad Prognosis: Esophageal and Gastric carcinoma ( all forms EXCEPT flat intramucosal)

T-cell lymphoma- Celiac Disease (intestines)
B-cell MALToma- H.Pylori (stomach)
Esophagus
Plummer-Vinson syndrome: iron deficiency anemia, dysphagia, esophageal web, and atrophic glossitis.
- esophageal web- mucosal folds- narrowing of lumen
- ring
Boerhaave syndrome: spontaneous rupture of the lower esophagus, a variant of Mallory-Weiss syndrome.

Stomach
H. Pylori:
- chronic atrophic gastritis Type B
- peptic ulcers
- adenocarcinoma of the stomach
- B-cell lymphoma of the stomach (in MALT tissue)
Counter-intuitive
- Shock, hypotension, and ischemia can be a cause of acutge erosive gastritis

Zollinger-Ellison syndrome:
Gastrin secreting tumor (gastrinoma) likely to arise in the gastrinoma triangle (pyloric area, duodenum, head of pancreas). The bigtime gastrin secretion causes lots of HCL secretion which leads to peptic ulceration
- Clinical Clue: presence of peptic ulcers in abnormal places ( small intestine, Meckel's diverticulum..aka places other than the duodenum) because there is sooo much acid secretion, it can not be effectively neutralized
- Also will see malabsorption symptoms because the excessive acid will deactivate pancreatic enzymes
Gastrinomas- can be in duodenum, pancreas and cause multiple peptic ulcers in stomach

Krukenberg Tumor: gastric diffuse carcinoma (signet ring micro form) that metastasizes to the OVARIES

GIST tumor: Gastrointestinal stromal tumor- probably originate stromal stem cells that are precursors of smooth muscle cells- classified as GIST and not a leiomyosarcoma if the cells retain the phenotype of undifferentiated stromal cells, most stain for c-KIT; histology shows spindle and epitheloid types, arise from muscularis propria (smooth muscle), can occur in stomach, or small/large intestines

Intestines
Omphalocele- congenital anomaly umbilical hernia

If GI bleeding: check for
- peptic ulcers (bleeding most common complication)
- gastritis
- hemorrhoids
If all these turn out to be negative, consider ANGIODYSPLASIA
ANGIODYSPLASIA
- older people
- tortuous dilatation of mucosal and submucosal blood vessels, prone to rupture
- maybe part of
o hereditary hemorrhagic teleangectasia
o CREST syndrome
- cecum/right colon

Celiac Disease
- Ab to gliadin (and glutaminases)= antiendomysial antibodies
- HLA-DQ2
- Flattening of villi
- Allergy to gluten, respond well to gluten free diet
- Predisposition to T-cell carcinoma
Non-neoplastic polyp
- hyperplasia
- hamartomatous
o Juvenile
o Peutz-Jeghers polyps- irregularly shaped glands surrounded by smooth muscles- multiple hamartomatous polyps scattered about
- lymphoid
- inflammatory pseudopolyps from UC
Pre-disposition to Cancer of Large Intestine
- Familial adenomatous polyposis- multiple polyps- loss of APC
- Familial NON-POLYPOSIS carcinoma (LYNCH syndrome)-
Cyclophosphamide: treats UIP and Wegener's Granulomatosis


LIVER

HLA linkage: Hemochromatosis

Central lobular congestion- hepatic venous HTN leading to the right ventricle

Limiting plate- connective tissue found around portal tract (hepatic vein, portal vein, bile duct)

Interface hepatitis- inflammation crosses the limiting plate and infects the hepatocytes around it (aka-piecemeal necrosis)

Interstitial cell of Ito- stores Vitamin A

MAJORITY of blood flow INTO liver is through portal vein
- MINORITY is via hepatic artery

Blood flow through hepatic lobule (periphery-central) is OPPOSITE of bile flow (central-periphery)
- both bile stagnation AND blood outflow stagnation will be evident in CENTRAL lobe
The first part of the billiary system is located in the central lobe in the intercellular billiary canaliculi

Gynecomasty from liver failure is a result of failure to detoxify hormones in male

ALT- alanine aminotransferase.

AST- aspartate aminotransferase.

Hepatitis A- directly hepatotoxic
HepB- indirectly hepatotoxic via induction of T-cell immune response- makes granulomas- ground glass appearance

Voluntary intoxication with Tylenol- common cause of emergency liver transplantation

Liver disease skin manifestations:
Spider Nevi
Palmar erythema
telangiectasis
a lesion formed by a dilated capillary or terminal artery, most commonly on the skin., can be a sign of liver disease- SPIDER NEVI- telangiectatic arteriole in skin with radiating capillary branches can be seen in liver disease

Spleenomegaly is also a manifestation of liver disease (remember that liver helps with old RBC metabolism)
- is often accompanied by thrombocytopenia- (decreased platelets) because if spleen is enlarged, the platelets will get caught in spleen (sequestration) and can't go into blood stream

Cholestasis= OBSTRUCTIVE jaundice

Unconjugated bilirubin does NOT show up in the urine (i.e.- hemolytic jaundice or any disorder with accumulation of unconjugated bilirubin)

Bile formation: (spleen) heme--biliverdin--albumin-unconj. Bilrubin--(liver) conjugated bilirubin (with glucouronides via uridine diphosphate-glucoronosyl transferase UGT1A1)---bile---(ampulla of vater)---intestines (metab to urobilinogen---feces (and some in urine)--enterohepatic recirculation as urobilogen
- unconjugated bilirubin (i.e. prehepatic is not soluable, so thus will NOT show up in urine if have pre-hepatic jaundice)
- in obstructive jaundice (cholestasis)- bilirubin is conjugated, so WILL see in urine
Alkaline phsophatase: in liver cell membrane lining intercellular canaliculi, if these levels are increased means OBSTRUCTIVE JAUNDICE Measure obst

Hereditary Hyperbilirubinemias:
Unconjugated:
Gilbert Syndrome: hereditary syndrome, most common form of hereditary jaundice, mild jaundice- unrelated to other symptoms- episodic jaundice (fluctuating hyperbilirubinemia) brought about by stress, exercize, fasting..genetic mutation in UGT1, reduced activity in UGT…no treatment, does not damage liver
-
Crigler-Najjar syndrome- hereditary jaundice, deficiency in UGT- can not conjugate bilirubin
- normal looking liver, really elevated levels of unconj bilirubin
- type I- enzyme absent- bad, type II- reduced enzyme activity- not as bad

Conjugated
Dubin-Johnson syndrome: impaired biliary excretion of bilirubin glucouronides due to mutation in canalicular multidrug resistance protein 2 (MRP2)- responsible for transport of bilirubin glucuronides and related organic acids into the bile
- liver is darkly pigmented- due to granules of epinephrine metabolites (not bilirubin), hepatocytes look otherwise normal

Rotor Syndrome: decreased hepatic uptake and excretion, liver looks normal, patients exhibit jaundice, but otherwise look normal

Alpha-1 antitrypsin defiency

Alpha-1 antitrypsin defiency: can cause conjugated obstructive jaundice, AND liver cirrhosis, and increases the risk of hepatocellular carcinoma
- most common form of neonatal hepatitis

Cholangiocarcinoma: malignancy of billiary tree, see tubular glandular structures surrounded by sclerotic stroma, gross- multiple lesions, maybe looks like metastasis, BUT the lesions are not indurated in the middle
Risk factors:
- primary sclerssinc cholangitis
- Congenital fibropolycystic diseases
- Most in West are spontaneous
- Orient: infection with opisthorchis sinensis (liver fluke)
Oral contraceptives
- cholestasis
- liver thrombosis (drug induced vascular changes in liver)
- liver cell adenoma (benign)

Kayser-Fleisher ring- present on cornea (limbus) in Wilson Disease

Alcoholic liver disease- increased blood ceruloplasmin
Wilson disease- DECREASED blood ceruloplasmin (ceruloplasmin is a copper transport protein)


Antibodies
- Antinuclear (ANA), Anti smooth muscle (ASM)---------Autoimmune hepatitis
- Anti-mitochondrial-------primary billiary cirrhosis
- P-ANCA------primary sclerosing cholangitis
Women:
- Young- auto-immune hepatitis
- Older-premenapausal- primary billiary cirrhosis

Most common causes of fatty liver
- obesity
- alcoholism
- diabetes

Spleenomegaly-----a symptom of liver cirrhosis--harder to pump blood into a cirrhotic liver (same mentality as portal HTN)
Cirrhosis----spleenomegally----asoc with thrombocytopenia---low platelet count