Non Viral Liver Injury

Front 1

drug induced liver injury

Back 1

-frequent cause of acute liver failure
-drugs can be metabolized by phase 1 and 2 or phase 2 conjugation
-unstable metabolites of drugs disrupt function of liver cells

Front 2

physio of drug induced liver injury

Back 2

1. disruption of hepatocyte: drugs bind to prot and dec ATP levels
2. Disruption of transport proteins: bile flow is interrupted >>>cholestasis
3. Immune response : from binding of drug to P450 enzyme
4. Death of liver cells from activation of tumor necrosis factor
5. Mitochondrial disruption

Front 3

Acetaminophen liver injury

Back 3

-most common cause of acute liver injury (prob- OTC!!!)
-can occur at therapeutic or excessive doses
-toxicity enhanced if pt is chronic alcohol user
-suicide attempts

Front 4

Acetaminophen liver injury: Clinical manifestations

Back 4

1. N/V
2. Rising hepatic aminotransfersae levels 24-48jrs after ingestion
3. Jaundice
4. Hepatic encephalopathy
5. Renal failure
6. Death
Dx: serum acetaminophen levels; time since ingestion; tx if serum acetaminophen levl is above toxic line

Front 5

Acetaminophen liver injury emergency mgmt and therapy

Back 5

-activated charcol PO 1-2hrs after ingestion (absorbs drugs and poisons)
-N-acetlycysteine (Mucomist)- effective is started within 8-10hrs of ingestion

Front 6

drug induced liver injury- Salicylates (aspirin)

Back 6

-Ingestion of 200 mg/kg of salicylate over several days can produce intoxication/poisoning
-acute: N/V, gastritis
-moderate: hyperpnea (deep rapid breathing), tachycardia, tinnitus, metabolic acidosis
-Serious: agitation, confusion, coma, seizures, cardiovascular collapse, pulmonary edema, hyperthermia, death

Front 7

Salicylates Dx and mgmt

Back 7

Dx: measure salicylate levels, evaluate blood gas for metabolic acidosis; >100mg/dL indicates severe poisoning
Mgmt: activated charcoal, gastric lavage (take everything out of stomach), Na bicarbonate
-alkalinization of urine
-hemodialysis

Front 8

many drugs cause liver injury!

Back 8

1. Amoxicillin
2. Cipro
3. Erythromycin
4. Fluconazole (can lead to hepatic failure)
5. Isoniazid
6. Sulfonamides
7. Methyldopa (C/I in pts with liver disease)
8 OCs
9. Valproic acid
10. Extasy
11. cocaine

Front 9

risk factors for drug induced liver injury

Back 9

1. Black and Hispanics higher risk for INH toxicity
2. Elderly pts
3. W>M
4. alcohol use
5. liver disease
6. genetic factors: differences in P450 enzymes
7. AIDs/Malnourishment

Front 10

Alcohol induced liver injury

Back 10

-can lead to fatty liver, alcoholic hepatitis, cirrhosis
-drinks >80g/day for M and 30-40 for W

Front 11

Alcoholic fatty liver (steatosis)

Back 11

-can be reversed
-drink >60mg ETOH/day
-mechanism unclear
-genetics, obesity and diet may play a role
-PE may be nml or hepatomegaly common

Front 12

Steatosis Labs and imaging

Back 12

-LFTs: AST > ALT
-Macrocytosis: incr mean cell vol common
-Carbohydrate deficient transferrin: sensitive and specific
-Check for Hep C, iron levels, TIBC
-US, CT, MRI (fatty liver more echogenic)

Front 13

Steatosis procedures and tx

Back 13

-liver biopsy
-no specific medical tx
-replacement of vit, minerals
-alcohol rehab
-counsel pts
-f/u care

Front 14

Non-alcoholic fatty liver disease (steatohepatitis)

Back 14

-fatty liver assoc with inflamm
-excess lipids within hepatocytes
-can progress to cirrhosis and hepatocellular carcinoma
-assoc with metabolic syndrome
-common in obsese pts
-most common liver disease in adolescents

Front 15

steatoheaptitis H&P

Back 15

-asymptomatic, fatigue, malaise, abd discomfort
-hepatomegaly
-splenomegaly, ascites, edema, spider angiomas, varices, gyncomastia
-check LFTs: may be nml or show 10fold inc
-lipids may be elvated

Front 16

steatoheaptitis medical care

Back 16

-no established treatment
-low fat diet
-wt loss
-exercise
-Bariatric surgery and gastric bypass seem to result in improvement

Front 17

Alcohol induced liver injury: Alcoholic hepatitis

Back 17

-Progressive inflammatory liver injury associated with long term heavy alcohol intake
-alcohol damages liver cell membranes
-The metabolism of ethanol results in free radicals and oxidative damage
-most common in Native Americans
-W more susceptible to adverse effects of alcohol

Front 18

alcoholic hepaititis H&P

Back 18

-multiple MVA's/DUI, problems with personal relationships
-FH
Fever/tachypnea/
tachycardia
RUQ pain
Liver enlarged, tender
Scleral icterus/dark urine
Splenomegaly
Asterixsis
Peripheral edema
Ascites
spider angiomata, proximal muscle wasting, altered hair distribution, gynecomastia

Front 19

alcoholic hepatitis dx

Back 19

-CVC: neutrophils, bands, mod anemia
-AST mod. elevated, ALT nl or mildly elevated, AST/ALT ratio >1
-Alkaline phosphatase mildly elevated
-GGT levels elevated
-Albumin low
-Bilirubin elevated
-PT prolonged
-CDT
-serum electrolytes: alterations due to vomiting, ketoacidosis, resp alkalosis
-liver biopsy can determine presence of cirrhosis

Front 20

Liver biopsies

Back 20

Percutaneous biopsy: performed at bedside by gastroenterologist or hepatologist
Transjugular biopsy: done via catheter placed in hepatic vein under fluoroscopic guidance.

Front 21

alcoholic hepatitis medical mgmt

Back 21

-cessation of alcohol
-oral or parenteral nutrition reverse malnutrition
-prot, vit, minerals, folic acid, thiamine
-salt restriction if ascites present
-corticosteroids may reduce short term mortality
-Pentoxifylline
-liver transplantation

Front 22

Cirrhosis

Back 22

-final stage of many forms of chronic liver disease
-characterized by fibrosis, deposition of collagens, glycoproteins, proteoglycans
-nml liver tissue is transformed into structurally abml nodules
-may occur over wks to yrs
-NOT reversible
-hep C and alcohlic liver disease are more common causes followed by non-alcoholic fatty liver disease and chronic hep B

Front 23

Complications of cirrhosis

Back 23

-portal HTN: Result of increased resistance to portal blood flow and increased portal venous inflow.
-spleen grows and sequesters plts and other blood cells -->bleeding prob
-Blood that normally flows into portal system is shunted to systemic circulation. Collateral vessels cannot keep up with portal blood flow.
-Esophageal varices (form with portal P's >12mmHg)--> Can rupture and cause hemorrhage!!
-Ascites

Front 24

treatment of esophageal varices

Back 24

-B blockers (propanolol): reduces portal P by producing splanchnic vasoconstriction and decreasing portal venous inflow.
-Endoscopic variceal ligation with rubber rings
-hospitalization
-vasoconstrictors: stomatostatin
-shunt therapy if bleeding persists (TIPS-Connects portal vein to hepatic vein bypassing liver to normalize portal pressure)

Front 25

Ascites

Back 25

-confirm dx with US
-paracentesis to check for: albumin, prot, WBC's, cultures and cytology (look for an infected process)
-Serum-Ascites Albumen Gradient and ascites protein levels: Serum ascites albumen gradient is >1.1 g/dL with ascites associated with hepatic sinusoid (cirrhosis, cardiac ascites)
-Protein levels of ascites represent integrity of hepatic sinusoid (Normal sinusoids “leak” protein. Sinusoids in cirrhosis do not leak protein)
-CHART!

Front 26

ascites tx

Back 26

-salt restriction
-diuretics-Spironolactone
-add flurosemide if inadequate wt loss or hyperkalemia
-if diuretics do no work, lar vol paracentesis with albumin replacement
-if reccurent, TIPS stent

Front 27

Hepatorenal Syndrome (HRS)

Back 27

-complication of cirrhosis
-renal dysfunction/failure
-caused by vasoconstriction of renal arteries with impaired renal perfusion
-pts have poor response to diuretics so may have to go to renal transplantation

Front 28

HRS dx

Back 28

-CC <40
-Serum creatinine >1.5
-urine vol <500ml/day
-urine sodium <10

Front 29

Spontaneous Bacterial Peritonitis (SBP)

Back 29

-complication of cirrhosis
-Most common organisms are E. coli, Strep pneumoniae, Klebsiella species and gram – enteric organisms
-asympt in 30% of pts
-fever, chills, diarrhea
-worsening encephalopathy
-ascities, renal failure, ileus
-abd tenderness
-hypotension
-jaundice

Front 30

SBP dx and tx

Back 30

-sampling of ascites fluid for neutrophils and culture
-SBP is neutrophil count >250 cells/u: with + bacterial culture
-blood and urine cx
-Cefotaxime
-repeat paracentesis in 48-72hrs to see dec neutrophil count

Front 31

Hepatic encephalopathy

Back 31

-complications of cirrhosis
-includes personality changes, intellectual impairment, depressed level of consciousness.
-memory changes, difficultly concentration, confusion, euphoria/depression, irritability, sleep disorders, drowsiness, lethargy
-inappropriate behavoir, inability to perform mental tasks, amnesia, fits of rage, coma

Front 32

Hepatic encephalopathy diagnostic studies

Back 32

-H&P
-elevated serum ammonia levels
-EEG
-CT or MRU of brain

Front 33

Hepatic encephalopathy tx

Back 33

-Correct causes of encephalopathy (ie: infection, GI bleeding, constipation, narcotics, sedatives)
-Lactulose stimulates passages of ammonia form tissues to gut and inhibits intestinal ammonia production
-Neomycin and other abx

Front 34

Cirrhosis clinical manifestations

Back 34

1. ssx of complications
2. anorexia/malnutrition
3. pruritis
4. hypogonadism (males)
5. osteoporosis

Front 35

Cirrhosis tx

Back 35

-used for complications
-good nutrition with adequate calories and protein
-antihistamines
-topical testosterone for hypogonadism
-calcium and Vit D
-liver transplantation

Front 36

Hemochromatosis (Iron Overload)

Back 36

-abnml accumulation of iron in parenchymal organs leading to organ toxicity
-Hereditary Hemochromatosis (HH) is an inherited disorder of iron metabolism
-untx can lead to cirrhosis, heart failure, DM, impotence and arthritis
-whites 6x higher than AA pts
-M>F

Front 37

Hemochromatosis (Iron Overload): clinical manifestations

Back 37

-symptoms usually begin 30-50yrs
1. liver disease
2. abd pain
3. skin pigmentation
4. DM
5. arhtropathy
6. impotence
7. cardiac enlargement
8. severe fatigue
9. wt loss
10. hepatomegaly
11. RUQ tenderness, fluid overload, conduction abnormalities
12. joint prob: MCP, PIP, knee,s feet, wrists, back neck

Front 38

Hemochromatosis (Iron Overload)- Labs and tx

Back 38

-Transferrin saturation: >50-60&
-Serum ferritin: >200-300mcg/L
-genetic testing
-tx with phlebotomy to remove excess iron; avoid iron supplements, citrus juice and alcohol

Front 39

Wilson's Disease

Back 39

-autosomal recessive disorder of cooper metabolism
-excessive deposition of copper in liver, brain, and other tissues
-SI keps absorbing copper and liver not getting rid of it
-leads to liver failure, encephalopathy, coagulopathy and death
-manifests as liver disease in kids then neuropsychiatric illness in young adults

Front 40

Wilsons disease clinical manifestations

Back 40

1. cirrhosis, acute hepatitis, hepatic dysfunction, hepatic failure
2. asymmetric tremor
3. dfficulty speaking
4. excessive salivation
5. ataxia
6. masklike facies (expression less)
7. personality changes
8. dystonia, spasticity, grand mal seizures, rigidity (latee)

Front 41

wilsons disease psychiatric

Back 41

1. emotional lability
2. impulsiveness
3. disinhibition
4. self injurious behavior

Front 42

wilsons disease signs

Back 42

1. Kaiser-Fleischer rings: golden green0brown deposition of copper in periphery of cornea
2. osteopenia
3. arthropathy
4. hemolytic anemia
5. kidney stones
6. jaundice
7. spider angiomas
8. palmar erythema

Front 43

Wilsons- Labs

Back 43

1. SGOT/SGPT
2. Serum ceruloplasmin levels <20
3. Urinary copper excretion is >100
4. Hepatic copper concentraiton >200

Front 44

Wilsons- Treatment

Back 44

1. Copper chelation with penicillamine (Enhances urinary excretion of copper and prevents copper overload. SE include nephrotoxicity, hematologic abnormalities, rash)
2. other chelators: Oral zinc acetate, triethylene tetramine dihydrochloride (trien) (fewer SE)
-LIfelong tx needed!
-restrict copper rich foods: shellfish, liver
-test water for copper
-OT, PT, speech therapy, psyc