CM - GI Study Guide

what is Hepatic Cirrhosis?

• how is it characterized?

late stage of progressive hepatic fibrosis characterized by distortion of hepatic architecture and formation of nodules

what are causes of hepatic cirrhosis?

• top 3?

• alcoholic liver disease (#1)

• primary biliary cirrhosis #2

• chronic hep B and C #3

• hereditary hemochromatosis

• AAT deficiency

• Wilson’s Disease

• NAFLD

• right heart failure w/ chronic liver congestion

what labs are specific for alcoholic liver dz?

ast/alt > 2 (d/t depletion of Vit B6, which is needed for ALT synthesis ) and 2x GGT (specific)

elevated GGT alone not enough to make diagnosis

what labs are indication for primary biliary cirrhosis?

positive anti-mitochondrial antibodies, positive ANA, high bilirubinemia, high alkaline phos (b/c cholestatic pattern), maybe do liver biopsy

what tests should you do if you suspect chronic hep b or c?

test for HBV replications

HBeAg, HbeAB, HBV DNA viral load plus hep c rna viral load

what labs indicate hereditary hemochromatosis? (3)

• in women vs. male?

• what is a high risk for cirrhosis?

• what other test can suggest HH?

Ferritin >200 in women and >300 in males mandate further testing, Ferritin > 1000 is higher risk for cirrhosis, transferrin saturation- >60% in males and >50% in women suggest HH

what labs should you do for wilson’s disease?

Low ceruloplasmin levels, 24 hour urine test, LFTS and liver biopsy

what lab will you see for alpha-1-antitrypsin def?

deficient AAT

what does NAFLD require?

•  may see minor elevations of LFTs- though will expect to see 1 out of the 5 cardiometabolic risk factors 

  • High BP → BP >130/85mmHg or specific antihypertensive treatment

  • Insulin resistance → fasting glucose >100 or T2D or treatment for T2D

  • BMI greater than equal to 25 or waist circumference >40 in males and >35 in females

  • Elevated TG levels >150; HDL <40 or lipid lowering treatments

  • Plasma HDL cholesterol: <40 in men and <50 in women or lipid lowering treatment

what are the physical findings in hepatic cirrhosis (stigmata)?

1. d/t altered estrogen (↑): testosterone (↓) ratios → Spider nevi, telangiectasias, palmar erythema, gynecomastia, testicular atrophy

2. d/t portal HTN → caput medusae, esophageal varices, hemorrhoids, splenomegaly, ascites

3. d/t hepatic congestion → hepatojugular reflux (HJR)

4. ○ d/t hepatocellular dysfunction/injury: jaundice (elevated indirect bilirubin), edema and ascites (due to low albumin levels), high APTT/PT levels, fetor hepaticus (ammonia-smelling breath), elevated AST and ALT, low BUN, high ammonia levels which leads to encephalopathy and asterixes (flapping tremor)

   1. AST and ALT can be pseudo-normal if there is no liver tissue left → levels go down

5. Anemia/pancytopenia

6. Dupuytren’s contracture

7. Parotid gland enlargement

what is oropharyngeal dysphagia?

problems with oropharynx, larynx, upper esophageal sphincter

oropharyngeal dysphagia - what do you struggle swallowing?

• struggle swallowing liquids → use liquid thickeners

what is the primary symptom of oropharyngeal dysphagia?

coughing, choking

what are the causes of oropharyngeal dysphagia?

1. Inadequate saliva production

2. Malignancy of smokers and drinkers 

3. Muscular diseases → dermatomyositis, scleroderma or polymyositis 

4. Neurologic disease → stroke, MG, MS, PD, CN dysfunction: discoordinated swallowing

5. Sensory problems with CN V, IX, and X

6. Motor problems with CN V, VII, IX, X, and XII

what is esophageal dysphagia?

problems with esophagus, lower esophageal sphincter, or cardia of stomach

what is a indication of esophageal dysphagia?

trouble swallowing solids → mechanical obstruction

solids and liquids → motility disorder

what are the symptoms of esophageal dysphagia? (6)

• what are primary symptoms?

1. Vomiting & chest pain → primary symptoms

2. FB sensation

3. Weight loss

4. Heartburn

5. Hematemesis

what are the causes of esophageal dysphagia? (4)

• what is a 2n1s?

1. Mechanical → hiatal hernia, GERD, Zenker’s diverticulum (pouch in upper esophagus d/t weak throat muscles), esophageal cancer, extrinsic masses of the mediastinum 

2. Strictures: due to longstanding GERD, malignancy, radiation, caustic ingestion, previous sclerotherapy for varices, complications of surgical anastomosis (2N-1S)

3. Autonomic dysfunction

4. Motility disorders → achalasia, diffuse esophageal spasm, scleroderma

what is dysphagia?

 difficulty passing solids/liquids from mouth to stomach 

● should never be ignored, often represents something serious

complication of dysphagia

 aspiration and malnutrition (weight loss, dehydration

achalasia

a loss of peristalsis in the distal esophagus and failure of the LES to relax (lower esophageal sphincter)

primary achalasia

absence of post-ganglionic inhibitory (the nerves that tell LES to relax are missing) → innervation of the LES → does not relax

secondary achalasia

• what is appearance on barium swallow?

cancer, scleroderma, or infectious disease destroys the myenteric plexus (controls gut motility)

○ Presents w/bird beak appearance on barium swallow

birds beak appearance on barium swallow 2n1s

secondary achalasia

what is treatment for achalasia?

esophageal dilation or botulinum toxin (relaxes LES by blocking ACH release)

what is diffuse esophageal spasm (DES)?

• what triggers it

intermittent dysphagia

triggered by acid reflux, stress, hot or cold food, or carbonated

beverages

what is scleroderma?

• what can it lead to/cause?

a multisystem disorder causing hypomotility of the lower 2/3 of the esophagus and failure of the LES to contract → GERD, ulcers, strictures

what is Primary biliary cirrhosis?

• what does it cause?

autoimmune disorder that attacks small intralobular bile ducts (intrahepatic) causing cholestasis

what is the presentation of primary biliary cirrhosis?

• what are 3 BIG ones?

• what is the pattern of liver enzymes?

• females 

● Pruritus 

● Glossitis 

● Clubbing 

● Osteoporosis / bone pain

● Hepatomegaly 

● yellowing of the skin 

● cholestatic pattern of liver enzymes 

● xanthelasmas/xanthomas (collection of cholesterol under skin)

what is treatment for primary biliary cirrhosis?

ursodeoxycholic acid (aka ursodiol or Actigall) to suppress hepatic synthesis and secretion of cholesterol and inhibit intestinal 

absorption of cholesterol → decreases bile salt production

what is hereditary hemochromatosis?

• autosomal dom or rec?

• what chromosome is affected?

• what does that chromosome normally do?

 autosomal recessive disease of excessive iron absorption and uptake by cells d/t mutations of the HFE protein on chromosome 6 which controls the interaction of transferrin and its receptors

what population is at highest risk for hereditary hemochromatosis?

pts w homozygous C282Y mutation

what are the symptoms of HH?

• what age in m and f

• when does it occur?

• 2n1s?

do not occur until an excess of 20g of iron accumulates (age 40-50 in men and later in females)

● lethargy, weakness, arthralgia

● bronze diabetic: bronzing of skin + DM1

● low FSH and LH → low testosterone, ED, anovulation, and

infertility

● EKG abnormalities, infiltrative or dilated cardiomyopathy,

conduction defects, sudden death

● unusual GI infections (Listeria, Yersinia, Vibrio)

how do you diagnose HH?

• what labs? (which is most imp?)

• what numbers for those labs?

• what imaging is esp good for HH?

• what is not necessary but you can use + why?

• what is different about iron accumulation and age w/ HH and secondary iron overlod?

• what indicates cirrhosis, what are you suspicious of and what do you do?

serum iron, TIBC, transferrin sat, serum ferritin

○ Fe/TIBC > 45%

○ transferrin sat >60% in males and >50% in females

○ ferritin >300 in men and >200 in women

● MRI (estimate iron deposition) and/or genetic testing

● liver biopsy is not necessary for diagnosis, but can help stage liver disease via hepatic iron index

○ HII: measures liver iron compared to pt's age to determine the presence of hereditary hemochromatosis (iron accumulation increases w age in pts w/HH, but not in pts w secondary iron overload)

● if ferritin >1000 (indicates cirrhosis), screen for hepatocellular carcinoma every 6-12m w U/S and AFP

what is the treatment for HH?

• what is it determined by? what’s the goal?

• when do you stop?

• do you still treat if they don’t have symptoms but they’re homozygous?

therapeutic phlebotomy - 1 unit of blood every 1-2w, determined by ferritin levels (goal is 50-150), hold when Hgb < 12.5 

● blood can be donated, but must be labeled as coming from a pt w hemochromatosis 

● all pts w homozygous hereditary hemochromatosis and evidence of iron overload should be treated regardless of symptoms

what should you avoid in HH?

• what is not helpful?

Chelating agents unless concurrent disorder of erythropoietin or a chronic hemolytic anemia

● Vit C (helps body absorb iron)

● alcohol (risk of cirrhosis)

● low-iron diet is not very helpful bc daily intake is so low

what is wilson’s disease?

• auto dom or rec?

• what causes it? (specific what spot?

• onset?

• what does it cause?

 autosomal recessive disease causing hepatitis and neuropsych problems d/t ceruloplasmin deficiency, leading to copper overload in the liver and CNS, especially the basal ganglia w onset in childhood

what are the S/sx of wilson’s disease?

• what is 2n1s? (2)

Kayser-Fleischer rings (copper rings around iris) 

● Neuro: tremor, rigidity, ataxia, slurred speech, risus sardonicus (uncontrollable grinning), drooling 

● Psych: personality changes, impaired concentration, declining intellect, behavioral problems, depression, paranoia, decreased awareness in surroundings 

● Heme: easy bruising, anemia, hepatosplenomegaly 

what is the treatment for wilson’s dz?

• how long?

• when do reversal of symptoms start?

: lifelong → reversal of symptoms begins in about 6m

● avoid foods w high copper (liver, shellfish, mushrooms, nuts,

chocolate, dried fruit, avocados)

● drink bottled vs tap water (bc copper in pipes)

● copper chelators (D-penicillamine)

● oral zinc (prevents absorption of copper)

● liver transplant if hepatic failure

what is AAT deficiency?

• auto dom or rec?

• what organs does it attack?

• what can it cause

autosomal recessive disease which causes early-onset emphysema, hepatitis, liver cirrhosis, and hepatocellular carcinoma w differing severity based on different mutations

(“attacks” liver and lungs)

what does not make AAT deficiency worse?

alc and viral hepatitis

what accelerates the onset of emphysema in AAT deficiency?

smoking

what is the presentation for AAT def?

• what might you see on labs?

• what about your skin?

• what conditions might they have?

● elevated LFTs

● alpha-1 antitrypsin levels <80 mg/dl

● alpha-1 antitrypsin genotyping

● jaundice

● chronic hepatitis, cirrhosis, and/or hepatocellular carcinoma

development

what is the tx for ascites?

• what should you avoid?

paracentesis (drain), diuretics (slowly add spironolactone and furosemide), sodium restriction, and avoiding NSAIDs and ACEIs (lower GFR → fluid retention), but fluid will still reaccumulate

what are the complications of hepatic cirrhosis? (top 2) (5)

• HCC

• esophageal variceal hemorrhage

• bacterial peritonitis

• GI infections w/ unusual pathogens (vibrio)

• hepato-renal syndrome

what is variceal hemorrhage?

• what is it caused by?

• what makes it worse?

• why is this important?

 → fatal bleeding 

■ caused by portal HTN 

■ made worse by elevated PT and thrombocytopenia 

■ accounts for 1/3 of deaths in pts w cirrhosis 

what is the prophylaxis for variceal hemorrhage?

Nadolol (non-selective BB) to decrease portal HTN

● surgical tx of portal HTN

○ Spleno-Pancreatic and Gastric Disconnection (SPGD)

○ Warren shunt:

○ Transjugular Intrahepatic Portosystemic Shunt (TIPS):

● variceal ligation

what is spleno-pancreatic and gastric disconnection (SPGD)?

ligation of the gastric and pancreatic veins and detachment

of the splenic vein from the portal system

what is warren shunt?

attaches the splenic vein to the L renal vein to

switch it from the portal system to the systemic system

what is transjugular intrahepatic portosystemic shunt (TIPS)?

connect the portal vein to the hepatic (systemic) veins,

bypassing the liver

what is the treatment for variceal hemorrhage? (4)

● Blakemore balloon tamponade

● blood transfusion

● IV somatostatin (vasoconstrictor)

• upper endoscopy w ligation or sclerotherapy (hard if bad hemorrhage)

what is hepato-renal syndrome?

• what organ is normal and what do you have to do for it to regain function?

• what is the median survival

diseased liver releases vasodilating substances → splanchnic (intestinal) vasodilation → activation of RAAS → vasoconstriction of systemic vessels, including kidneys → underfilling of the kidneys 

■ kidneys are still normal and can regain function if liver disease is reversed ■ median survival is 3m if not fixed 

(portopulm HTN and hepato-pulm syndrome included)

what is treatment for hepato-renal syndrome?

treat underlying liver disease if possible, Midodrine (selective alpha 1 agonist) and Somatostatin to reduce portal HTN, Hemodialysis

what is portopulmonary HTN?

• what increases? what does it mean?

• what does it result in?

toxins that the liver cannot filter= release of vasoactive vasoconstrictors= increase in dead space (good ventilation and poor perfusion), resulting in hypoxemia and decreased blood to the left atrium

what is hepato-pulm syndrome?

• what does it increase? what does that mean?

• what is the result?

 toxins in the liver cannot filter= vasoactive substances release vasodilators= increased shunting= hypoxemia and decreased blood to the left atrium

what criteria is used to assess hepatic failure?

Childs-Pugh Classification: system used to determine prognosis of liver failure based on:

● presence of ascites

● bilirubin levels

● albumin levels

● prothrombin time or INR

● presence of encephalopathy

what are tests of liver cell injury/inflammation?

○ AST

○ ALT

○ GGT

○ 5’ nucleotidase

what are tests of liver synthetic fxn (ability to make things)?

• what do they indicate?

○ Serum Albumin

■ normal levels suggest an acute process (viral hepatitis, choledocholithiasis)

■ low levels suggest a chronic process (end stage cirrhosis, cancer)

○ Prothrombin Time

■ elevated levels indicate Vit K deficiency, malabsorption of Vit K, presence of Vit K antagonist, or significant hepatocellular dysfunction

■ if levels fail to correct after IM Vit K → hepatocellular injury

what are 4 tests of liver detox and transport?

• bilirubin (esp conjugated)

• serum ammonia

• BUN

• alk phos

what is unconjugated bilirubin?

• can it be measured?

• does it tend to be over or underestimated + why?

bilirubin that is either free or bound to albumin and has not yet been altered by the liver

● cannot be measured in serum → can be calculated, but tend

to be underestimated b/c…

• some of the bilirubin binds to azobilirubin and is counted as conjugated bilirubin

• free bilirubin reads as CONJUGATED

• covalently bound bilirubin to albumin

what causes elevation unconjugated bilirubin?

transfusion reactions, viral hepatitis, cirrhosis,

autoimmune hemolysis, gilbert syndrome

what is conjugated bilirubin?

• can it be measured

• over or underestimated?

bilirubin that has been altered w

glucuronic acid and becomes water soluble

● can be measured in serum, but tends to be overestimated

what are the causes of elevated conjugated bilirubin?

alcoholic liver disease, scarring of the bile ducts, gallstones, tumors, drugs, viral hepatitis

what is cholestatic liver pattern?

disproportionate elevation of alkaline phosphate compared to AST and ALT, often accompanied by elevated conjugated bilirubin

what is hepatocellular injury pattern?

disproportionate elevation of AST and ALT compared with alkaline phosphatase, often accompanied by elevated indirect (unconjugated) bilirubin → indicates liver is not working

what is mixed cholestatic and hepatocellular injury pattern?

increases in all LFTs d/t too much heme for a healthy liver to handle (hemolysis)

what are causes of elevated transaminases/LFTs?

• top 4?

• other common causes (4)?

• non-hepatic (5)

○ Fatty liver disease

○ Toxic/chemical hepatitis

○ Hepatitis B and C

○ Hemochromatosis

○ Autoimmune hepatitis

○ Wilson’s disease

○ Alpha 1 Antitrypsin Deficiency

○ Cholestatic disease

○ Myopathies

○ Thyroid Problems

○ Iron deficiency

○ Celiac disease

○ Adrenal insufficiency

what nodules suggest abd malignancy?

○ Virchow's node (enlarged L supraclavicular lymph node) and Sr. Mary Joseph’s nodule (periumbilical lymph nodes) suggest abd malignancy

what is hep A?

• transmission

• acute or chronic

• lab

○ fecal-oral transmission, including oral sex practices 

○ acute illness only, never chronic (usually present for 3-4w, but up to 6m)

○ ALT>AST before jaundice occurs

what are diagnostics for hep A?

• why is ordering them together helpful?

■ IgM is the first marker and is predominant for the first 3m, but can be elevated for up to 12m

■ IgG elevates in convalescence (after illness) and stays elevated indefinitely

■ if ordered together, can determine acute vs resolved infection

how to prevent hep A?

■ give Hep A Immune Globulin if exposure suspected and no previous active/passive immunity, preferably within 2 weeks of exposure

■ vaccines: dose at age 1+ and another dose 6-12m later

what is hep B (dane particle) transmission?

○ DNA virus

○ transmitted by body fluids

■ high concentration in blood

■ moderate concentration in semen, vaginal fluid, and saliva

■ low concentration in urine, feces, sweat, tears, breast milk)

hep B acute or chronic? what can it cause?

• what are 2 “subgroups”

○ can be acute or chronic → chronic (>6m) can cause cirrhosis and hepatocellular carcinoma

Mild persistent= carrier for life, asymptomatic

Chronic active= symptomatic everyday

what are the symptoms for hep B?

• prodrome vs. icteric

• what about the prognosis?

■ Prodrome: 1-2w of fever, joint pain, rash, malaise, N/V/D, headaches, weight loss, anorexia, loss of taste (dysguesia)

■ Icteric Phase: weeks 2-10 of jaundice, tea colored urine, liver tenderness, malaise, anorexia

■ 90-95% recover in 6m w lifelong immunity

what are the diagnostics for hep B?

core, envelope, and surface antigens and antibody

hbcag

caused by active infection

hbcab

appears later, persists for life

means you had prior infection

● NOT formed in response to vaxes

“i had hep B and it shook me to the core”

hbeag

 represents high infectivity when present in the acute phase of illness

hbeab

represents low infectivity when present during acute illness

hbsag

• what does it mean if it’s persistent for >6 months with or without LFTs/s/sx?

 the earliest marker, indicating infected state (acute or chronic)

● if persistent for >6m and in the absence of elevated LFTs or S/S = carrier 

● if persistent for >6m and in the presence of elevated LFTs or S/S = chronic infection

what is hbsab

represents immunity (from past infection or from vax)

treatment of active dz for hep b

antiviral drugs IF there is fulminant acute hepatitis

HBIG - hep B immunoglobulin

Otherwise → supportive care and monitoring for clearance/immunity

treatment of chronic hep B

• when meds vs. not?

immune system keeps Hep B under control, generally no tx (don’t want resistant)

HOWEVER IF advanced fibrosis with high serum HBV DNA OR reactivation of chronic HBV after chemotherapy/immunosuppression = treatment is interferon + antivirals x 1 yr

what is the prevention for hep B?

• when do you absolutely want to give vax - after diagnosis of what?

■ Hep B IG given if exposure

■ give Hep B IG at birth if mother is HBsAg+

■ vax doses at 0, 1, and 6m

■ 3 dose regimen for any risk group and healthcare workers

■ immediate vax after diagnosis of DM (1 or 2) btw the ages of 20-59

what is hep C?

• transmission

• acute vs. chronic

• how often is recurrence after transplant?

○ transmitted blood to blood 

○ associated w a broad range of clinical conditions other than liver disease, but most acute infections are asymptomatic 

○ many become chronic if untreated → develop cirrhosis → require liver transplant

○ recurrence post transplant occurs in >95% of pts 

○ no vaccine exists

how to diagnose hep C?

• how long does it take after exposure to become positive?

: presence of anti-Hep C antibody

■ takes 2-6m after exposure to become positive

what is treatment for hep C?

■ pts must be alcohol and IVDU free for 6-12m before treatment is initiated

■ vaccinate against Hep A and B

■ genotyping must be done to determine the type of infection

■ interferon + antiviral (interferon must be injected and has severe side effects)

■ monitor anti-Hep C antibody levels to monitor response to treatment

• monitor for cirrhosis, HCC, esophageal varices

what is hep D?

• why?

• treatment?

• prevention?

○ requires co-infection w Hep B for synthesis of its envelope protein

○ no specific treatment other than treating Hep B as indicated

○ there is no marker that persists long-term to indicate past infection ○ prevent w Hep B vaccine or prophylaxis

what is hep E?

○ does not have an envelope

○ intestinally transmitted

○ causes illness similar to Hep A, but less severe

○ no chronic infection

○ no testing available

what is hep G?

○ often co-infected by Hep B or C or both, but not required

○ associated w IVDU and blood transfusion, suggesting blood transmission ○ usually mild and brief

○ diagnosis by presence of Hep G RNA in blood

what is acute hepatitis?

• how fast does it need to resolve

• symptoms

must resolve w/in 6m

○ abd pain or distention, anorexia, N/V, weight loss

○ dark urine, pale or clay colored stools

○ fatigue, fever

○ jaundice, itchiness

what is autoimmune hepatitis caused by?

• what does it coexist with?

• what do you need to r/o

asymptomatic or symptomatic hepatitis d/t anti-nuclear antibodies or anti-smooth muscle antibodies

often coexists w other (often autoimmune) diseases (hemolytic anemia, ITP, T1 DM, thyroiditis, celiac disease)

○ must r/o infectious hepatitis

what are indications for liver transplant?

• what is most common indication in kids?

● Hep C (#1)

● alcoholic liver disease (#2)

● idiopathic/autoimmune liver disease

● primary biliary cirrhosis

● primary sclerosing cholangitis

● acute liver failure

● hepatitis

● metabolic liver disease

● cancer

● Biliary Atresia (most common indication in kids)

what is budd-chiari syndrome?

• what is the triad?

thrombosis of the hepatic veins anywhere from the hepatic venules to the right atrium, presenting w a classic triad of abd pain, ascites, and hepatomegaly

what is associated with budd-chiari syndrome in order? (7)

polycythemia vera (#1)

○ pregnancy

○ postpartum

○ OCPs

○ paroxysmal nocturnal hemoglobinuria

○ hepatocellular carcinoma

○ lupus anticoagulant

what makes up bile?

bile acids, bile pigments, cholesterol, water, phospholipids, electrolytes

what makes a bile acid?

cholic acid and chenodeoxycholic acid

what are the bile pigments?

waste products of the liver including bilirubin and biliverdin

■ give feces brown color

what are the bile acid dependent components?

• what secretes them?

bile acids, bile pigments, cholesterol, and phospholipids secreted by hepatocytes