8.4 (10.4) Jaundice, ascites, and encephalopathy Flashcards by Shannon Bunn

List THREE categories of unconjugated hyperbili causes and TWO example of each.

◆ Bili overproduction
- Hemolysis
(e.g. sickle cell, autoimmune hemolytic anemia, hereditary spherocytosis, TTP/HUS)
- Ineffective erythropoiesis
(e.g. severe iron def anemia, thalassemia, megaloblastic & sideroblastic anemia, erythropoietic porphyria, erythroleukemia)
- Hematoma reabsorption
- Too much transfusions

◆ Poor liver uptake
- CHF
- Portosystemic shunt

◆ Impaired conjugation by liver
- Gilbert’s syndrome: inherited d/o dec in bili-UGT activity
- Crigler-Najjar syndrome
- Rotor syndrome

Box 8.4.1

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List THREE top causes of hepatic jaundice worldwide + THREE other causes

◆ Top 3 causes worldwide:
- viral hepatitis (esp hep B and C)
- ETOH liver disease
- non alcoholic fatty liver disease (NAFLD)

◆ Other causes (DIMS)
- drugs: immunotherapy, tylenol, nsaid, abx, accutane, herbs
- infection: septicemia (bacterial, viral)
- metabolic: parenteral nutrition
- structural: tumor infiltration, congestive hepatopathy, hypotension (infarct, severe valvular dz), Budd–Chiari syndrome (aka hepatic venous outflow obstruction)

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List TWO malignant and TWO benign causes of obstructive jaundice. Which type of bilirubin is elevated?

◆ Malignant:
- carcinoma of the head of the pancreas
- cholangiocarcinoma
- mets to the liver

◆ Benign:
- gallstones (16% of obs jaundice)
- pancreatitis
- parasitic infections
- primary sclerosing cholangitis
- stricture post invasive procedure

Both conjugated and unconjugated inc - but conjugated higher

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Obstructive jaundice - from where to where can be obstructed?

Any point with in the liver -> ampulla of Vater

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List three medications that (other than tylenol) are associated with idiosyncratic reactions causing liver injury and hepatic jaundice.

◆ antibiotic (amox clav, flucloxacillin, cipro)

◆ anti-inflamatory (NSAIDs)

◆ immune checkpoint inhibitors (eg. ipilimumab, pembrolizumab, nivolumab)

◆ herbs

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Initial bloodwork for jaundice

◆ CBC (plt)
◆ Total bili, unconjugated and conjugated
◆ LFTs
◆ Liver function: albumin, INR/PT

FS: complications
- Ammonia (hep enceph)
- e7 (Hepatorenal)

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List four imaging studies that can be done for assessment of jaundice.

◆ Ultrasound (transcutaneous)
- 1st imaging choice in the pt w/ jaundice.

◆ Endoscopic ultrasonography (EUS)
- more sens for pancreatic & ampullary cancers

◆ Magnetic resonance cholangiopancreatography (MRCP)
- same accuracy as direct cholangiography w/ no cannulation risk

◆ Endoscopic retrograde cholangiopancreatography (ERCP)

◆ Computed tomography w/ contrast
- better imaging than percutaneous US of liver

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What is Budd-Chiari syndrome?

For patients with appropriate goals of care, what are TWO interventions used to treat acute Budd-Chiari syndrome

Occlusion of the hepatic veins
- Primary = Thrombus
- Secondary = Tumor

◆ Transjugular intrahepatic portosystemic shunt (TIPS)
- shunt placement to connect portal vein and hepatic vein
Sup mesenteric vein + splenic vein + gastric vein -> portal vein -> liver -> hepatic vein -> IVC -> heart

◆ Hepatic vein stent

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Name biliary drainage procedures

◆ Biliary drains (External vs Internal/External)

Surgical bypass - surgeon
endoscopic (ERCP) - GI
percutaneous (PTC -percutaneous transhepatic cholangiogram) - IR

FS: ERCP most common

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In what TWO situations would a PTC drain be preferable to ERCP stenting in setting of obstructive jaundice

◆ high bile duct obstruction

◆ distorted duodenal anatomy
- due to previous surgery or presence of local tumour

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What is the correlation between serum bilirubin levels and subjective experience of pruritus? What is better associated?

◆ No correlation to serum bili or stage of liver dz

◆ Associated with circadian rhythm
- seems to be worse between 1200-1800

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Chronic cholestasis can lead to difficulties in absorbing certain vitamins - which ones? What is one complication of this?

◆ Fat soluble - ADEK
- vitamin K def causes inc INR -> inc risk bleeding

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Mechanism of cholestasis induced pruritis

1) Inc circulating bile acids & puritogens

2) Increased autotaxin

3a) Stimulating peripheral itch receptors within skin
and/or
3b) Central neural mech resulting in alterations in NTs (opioids, serotonin, GABA)

FS:

Bile is excreted into the small intestine to help solubilize fat and VIT ADEK
Majority is reabsorbed in ileum into portal vein -> liver

Bile = cholesterol + bile acid (bile salt) + bilirubin

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Name three ways rifampin is proposed to relieve pruritus

◆ Liver: Inhibition of bile acid uptake by hepatocytes*

◆ Liver: Hepatic enzyme inducer (increase metabolism of pruritogens)*

◆ Reduction in circulating levels of autotaxin

◆ Gut: Alteration of bowel flora (decreasing re-uptake of bile acids and pruritogens)*

◆ Central opioid antagonism

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List four non pharm interventions for pruritus

◆ Topical emollients

◆ environmental measures to cool and lessen sweating

◆ keeping finger nails cut short

◆ wearing cotton gloves at night to lessen damage to the skin through scratching

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Outline FIVE mechanisms by which cancer causes malignant ascites

◆ Peritoneal carcinomatosis (53%)

◆ Massive liver mets causing portal hypertension
◆ Two of the above causes in combo
◆ Budd chiari syndrome due to cancer occluding hepatic veins
◆ HCC + cirrhosis
◆ Chylous ascites due to malignancy

FS:
- Exudative: Peritoneal carcinomatosis
- Transudative: Portal HTN due to Budd Chiari syndrome, cirrhosis, liver mets (3)
- Chylous ascites

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What is SAAG, what does it indirectly measure? What does a high SAAG vs low SAAG indicate?

◆Serum to ascitic albumin gradient
- measures portal hypertension

◆ High SAAG (>11mg/L) = portal hypertension -> transudative ascites
(e.g. cirrhosis, BUDD chiari syndrome, alcoholic hepatitis, massive liver mets, portal vein thrombosis)

◆ Low SAAG = exudative ascites
(malignancy like peritoneal carcinomatosis, infection, inflammation)

What is chylous ascites? How does it happen

◆ TRI-GLYCERIDE rich ascites as a complication of:

retroperitoneal tumour spread or its treatment –>
damage to lymphatic vessels / obstruction of lymphatic flow through lymph nodes or pancreas

How to tx chylous ascites due to cancer ? Name 3 methods

◆ Chemotherapy
◆ Statin
◆ TPN

How does the prognosis after the first presentation of malignant ascites in ovarian cancer differ from other cancers?

◆ Have a longer mean survival from the time of development of ascites when compared to those with other malignancies

Name the TWO mainstay txs of ascites of non-malignant origin

◆ Diuretic
◆ Na restriction

What diagnostic test may indicate that a patient with malignant ascites may respond to diuretics? What two diuretics are reasonable to try (what ratio):

◆ High SAAG (>11mg/L) and raised plasma renin

◆ Spironolactone 50mg to furosemide 20mg daily
(max 400mg:160mg)

A patient with malignant ascites and a SAAG of 4 has a paracentesis with 5L of fluid removal. What features would make you consider providing IV fluid replacement?

◆ Hypotensive (decrease BP)

◆ Severe renal impairment (decrease GFR)

◆ Dehydration

List THREE complications of paracentesis

◆ Leakage

◆ Bowel perforation

◆ Peritonitis

◆ Localized cellulitis at the drainage site

What subset of patients with malignant ascites may be prone to hypovolemia following large-volume paracentesis?

◆ Without peripheral edema or ◆ High SAAG + no diuretic response

Procedure to consider for cirrhotic ascites

◆ Transjugular intrahepatic portosystemic shunt (TIPS) - the pressure inside the portal veins is decompressed into the systemic circulation.

List FIVE biochemical indicators that indicate a patient presenting with a first episode of hepatic encephalopathy has a worse prognosis than baseline

Low albumin, high bili, high prothrombin activity, high ALP High potassium, high urea Not in 6th ed. FS: think liver + renal

Pathophysiology of hepatic encephalopathy

◆ Inc levels of ammonia in the sys circulation come principally from: - portosystemic shunting - reduction in the processing capacity of the liver - dec muscle mass and renal dysfunction further contribute to hyperammonaemia, as these organs have the capacity to break down ammonia as well ◆ In the brain ammonia: - directly inhibits both excitatory and inhibitory postsynaptic potentials - disrupts synthesis of neurotransmitters - causes an increase in production of reactive O & N species - leads to inc intracellular osmolarity with edema ◆ Intestinal bacteria produce other potential central neurotoxins such as benzodiazepine-like compounds, mercaptans, phenols, and short- and medium-chain fatty acids - all found in relatively high levels in individuals with chronic liver disease and may contribute to HE. WP: too much detail? FS: - Gut produce ammonia -> systemic circulation - Liver disease -> portosystemic shunt (blood away from liver) -> ammonia cannot be converted in liver to urea (which is cleared renally) - Increased ammonia in systemic circulation -> brain -> HE

A patient presents with hepatic encephalopathy. List FOUR precipitants that you need to consider as you create a tx plan for this patient

◆ Dehydration, uremia ◆ Metabolic derangements (low K, low glucose) ◆ Sedation - Drugs: benzodiazepines, opioids, alcohol and other sedatives - Infection - Anemia/GI bleed - Hypoxia ◆ Constipation FS: think DIMS for delirium

What is the American Association for the Study of Liver Disease and the European Association for the Study of the Liver classification of HE stage 0 & 1?

◆ Stage 0: - lack of detectable changes in personality or behaviour - min changes in memory, concentration, intellectual function, and coordination - asterixis is absent ◆ Stage 1: - trivial lack of awareness w/ a dec attention span. - hypersomnia, insomnia, or inversion of sleep pattern are classic features of this stage - patients may complain of euphoria, depression, irritability, and mild confusion - there is slowing in their ability to perform mental tasks, particularly addition and subtraction. - asterixis may be detected

What is the American Association for the Study of Liver Disease and the European Association for the Study of the Liver classification of HE stage 2?

◆ Stage 2: - lethargy, drowsiness, or apathy develops. - there may be inappropriate behaviour reported by those close to the patient. - slurred speech, gross deficits in ability to perform mental tasks - obvious personality changes - intermittent disorientation can be seen (particularly regarding time - asterixis is obvious and spontaneous

What is the American Association for the Study of Liver Disease and the European Association for the Study of the Liver classification of HE stage 3?

◆ Stage 3: - patients are somnolent but can be aroused - they are unable to perform mental tasks - have gross disorientation regarding time and place. - have marked confusion, associated with amnesia, occasional fits of rage, and often incomprehensible speech. - Muscle rigidity, clonus, and hyperreflexia have replaced asterixis on physical examination.

What is the American Association for the Study of Liver Disease and the European Association for the Study of the Liver classification of HE stage 4?

◆ Stage 4: - patients are comatose with or without response to painful stimuli - decerebrate posturing may be seen. FS: summary of five stages Stage 0 - LOC - normal - Cognition - mild changes - Exam - normal Stage 1 - LOC - hyper/insomnia - Cognition - slow - Exam - May have asterixis Stage 2 - LOC - lethargic - Cognition - grossly slow, intermittent disorientation - Exam - Obvious asterixis Stage 3 - LOC - drowsy but rousable - Cognition - very disoriented - Exam - Myoclonus, rigid, hyper-reflexia Stage 4 - LOC - comatose - Cognition - comatose - Exam - decerebrate

How is covert encephalopathy (stage 0+1) identified?

◆ Specific neuropsych testing - number connector test, block design test, digit symbol test

Management approach of hepatic encephalopathy

◆ Environmental support (like in delirium) ◆ Family and caregiver education/support ◆ Treat precipitants ◆ Hydration ◆ Lactulose 10-30 mL/day w/ titration to 2-4 soft stools per day (oral, NG ,rectal) ◆ ABx to reduce urease producing bacteria in intestine - metronydazole, ampicilin, rifaximin FS- - Lactulose + Rifaximin/flagyl/ampicilin - Hydration - Management of delirium (source, symptoms) - Educate

A patient with hepatic encephalopathy is placed on lactulose. An order is written for 45mL of lactulose q3h. The patient is having very frequent loose BMs. The hepatic encephalopathy appears to be getting worse. A delirium work up is done that shows sodium of 155. What will do you? Why?

◆ The maintenance of circulating blood volume by correction of dehydration is important to maintain adequate renal excretion of ammonia ◆ Give fluids, hold lactulose - goal is 2-3 loose BMs per day

A patient with hepatic encephalopathy is placed on lactulose. An order is written for 30mL of lactulose TID. The patient is having 2-3 loose BMs per day. The hepatic encephalopathy appears to be getting worse. A delirium work up is done. Nothing new is found. What will you do? Why?

◆ Trial of rifaximin ◆ Several trials have demonstrated its efficacy in relieving symptoms of encephalopathy, reducing blood ammonia levels and improving electroencephalographic abnormalities

List FOUR complications of ERCP/PTC

◆ Bleed ◆ Biliary leak ◆ Acute pancreatitis ◆ Bacterial cholangitis

What does PTC stand for and what intervention is usually done?

◆ Percutaneous Transhepatic Cholangiogram - Percutaneous Biliary Drainage (PBD)

List the SIX complications (6) of a peritoneovenous shunt (shunt placed into ascites and then tunnelled under the skin to the systemic circulation, usually the internal jugular or femoral veins)*

◆ Most common: - lumen occlusion as a result of thrombosis - DIC ◆ Less common: - fluid overload with pulmonary edema - thromboembolism - vena caval thrombosis - hepatic encephalopathy - peritonitis - tumor seeding to SC of ant abdo wall

Name FOUR pharm tx for cholestasis induced pruritis

◆ Removal of puritogens - cholestyramine, colestipol, colesevelam ◆ Enzyme induction - rifampin ◆ Opioid antagonist - naloxone, naltrexone ◆ Serotoninergic systems - sertraline, paroxetine