Exam 2 Flashcards
(G) Pancreatitis: Endocrine function
Glucose homeostasis regulation
- Beta cells (insulin), alpha cells (glucagon), D cells (somatostatin)
(G) Pancreatitis: Exocrine function
Acinar cells: digestive enzymes (lipases, carbohydrase, peptidase)
(G) What is acute pancreatitis?
Painful episodic inflammation
- may lead to chronic pancreatitis
(G) What is chronic pancreatitis?
Inflammatory condition affecting the pancreas and involves progressive, irreversible damage to the pancreatic tissue
(G) Chronic pancreatitis results in ___, ____, and ____
Loss of glandular function (endo/exo), fat malabsorption (steatorrhea), and protein maldigestion
(G) CP treatment: loss of function
Pancreatic enzymes (lipase, amylase, and proteases) insulin
(G) CP treatment: pain
Delivery of active proteases to the duodenum to repress CCK secretion
(St) What causes acute pancreatitis (AP)?
- Gallstones
- Chronic alcohol abuse
- Pancreatic cancer
- Hypertriglyceridemia
- Drugs (rare)
(St) S/S, lab tests of AP
- Abrupt onset of severe persistent epigastric or LUQ pain that typically radiates to back
- N/V
- Voluntary guarding
- Elevated amylase and lipase
(St) How is AP diagnosed?
At least 2 of the following:
1. Characteristic abdominal pain
2. Serum amylase >= 3x ULN (N: 0-130): not pancreatitis specific: increased by renal, hepatic, cancer
3. Serum lipase >= 3x ULN (N: 20-180): pancreatitis specific
(St) Characteristic findings on CECT or MRI with AP (2 types of AP)
- Interstitial edematous AP: focal or diffuse pancreatic edema
- Necrotizing AP: focal or diffuse areas of pancreatic necrosis
(St) Severity of AP: Mild
- Characteristics
- Local complications
- No organ failure
- No local complications
- Generally marked improvement ( & return to oral feeding) w/i 48 hrs
(St) Severity of AP: Moderately Severe
- Characteristics
- Local complications
- Local complications &/or transient organ failure (<48 hrs)
- Fluid collections, pseudocysts, sterile/infected necrosis
(St) Severity of AP: Severe
- Characteristics
- Local complications
- Persistent organ failure (> 48 hrs)
- Early severe (=< 7 d): SIRS &/or organ failure, GI bleed, serum Cr >=2
- Late severe (> 7 d): sepsis
(St) Severity of AP: Determine SIRS criteria
2 or more of the following
- Fever >38.3 C (100.9F) or <36 C (96.8 F)
- HR > 90 bpm
- Respiratory Rate > 20 bpm or PaCO2 < 32 mmHg
- WBC > 12,000/mm3 or < 4,000 mm3 or >10% bands
(St) Indications of ICU admissions for AP
- Age > 55
- BMI > 30 kg/m2
- APACHE-II >8 during first 24 hr
- SIRS for >48 hr
- Pleural effusions or infiltrates
- Decr mental status
- Underlying cardiac/pulmonary disease
- BUN > 20mg/dL, Hct >44%, or serum Cr > 1.8 mg/dL
- HR <40 or >150
- SBP <80, MAP <60, or DBP >120
- RR >35
- PaO2 <50
- Arterial pH <7.1 or >7.7
- Serum Na <110 or >170, K <2 or >7, glucose >800, or Ca >15
- Anuria
- Coma
(St) Treating ICU AP patients (4)
- Early aggressive hydration: 0.9% NS or lactated Ringer’s over 12-24 hrs
- Pain management: IV opioids hydromorphone or morphine (PCA > IVP)
- Nutrition
- IV antibiotics: empiric antibiotics indicated with necrotizing pancreatitis showing systemic signs of infection (fever, leukocytosis, organ dysfunction)
(St) Treating ICU AP patients:
- Nutrition for mild AP
- Oral intake typically resumes in 3-7 days
- Can start with clear liquids or solid low-fat diet
(St) Treating ICU AP patients:
- Nutrition for moderately severe to severe AP
- Enteral feeding
- Nasogastric/jejunal equally safe and effective
- Start with regular formula, switch to peptide-based formula if not tolerated
- Pancreatic enzyme supplements once enteral feeding initiated
(St) Treating ICU AP patients:
- Antibiotics: gram negative bacteria
- Carbipenem
- Fluoroquinolone + Metronidazole
- 3rd/4th gen Cephalosporin + Metronidazole
- Pip/Tazo (Zosyn)
(St) Treating ICU AP patients:
- Antibiotics: gram positive bacteria
Vancomycin
(St) Potential etiologies of fever and relapsing AP
- Pancreatic abscess or necrosis
- Infected pseudocyst
- Nosocomial pneumonia
(St) High neutrophils (segs, bands) indicate higher chance of ____
Bacterial
(St) High lymphocytes indicate higher chance of ____
Viral
(St) Causes of Chronic Pancreatitis (CP)
- Chronic alcohol abuse
- CF, pancreatic cancer, hypertriglyceridema
(St) Clinical symptoms of CP
- Abdominal pain (worsen after eating)
- Fat malabsorption (steatorrhea: mild = 7-15 g/day fat, severe = >15 g/day), diarrhea, weight loss
- Diabetes
- Duodenal ulcers, biliary cirrhosis
(St) Diagnosis of CP
- High serum amylase and lipase during acute, often normalize as disease progresses
- Fecal fats: steatorrhea does not begin until disease is advanced
- Imaging: Endoscopic retrograde cholangiopancreatography (ERCP), ultrasound/CT
(St) Management of CP (3)
- Chronic pain management: eliminate contributing factor -> APAP or NSAID -> opioid
- Dietary fat restriction: small, frequent meals, medium chain TG
- Pancreatic enzyme supplements
(St) Management of CP
- Pancreatic enzyme supplements: goal, dose, AEs
- 25,000-40,000 units of lipase to duodenum with each meal or snack
- Must be taken with each meal or snack, swallow whole with a full glass of water
- Dose must be individualized
- AEs: N/D, abdominal pain, constipation, bloating, hyperuricemia/uricosuria, hypersensitivity
HBV vs HCV
- DNA/RNA, manageable/curable
- HBV: DNA, manageable
- HCV: RNA, curable
HBV routes of infection
Parenteral, sexual, perinatal
HBV Physical exam
- Icteric sclera, skin, secretions
- Decreased bowel sounds, increased abdominal girth
- Asterixis
- Spider angiomas
HBV Pathology
- Nodules of damaged & regenerating hepatocytes
- Fibrous bands > cirrhosis > HCC
- Ground-glass cytoplasm (light)
- Bile pigment accumulation (dark)
HBV structure: HBsAg
Surface antigen
- Most abundant antigens
- Detectable at onset of clinical symptoms
HBV structure: HBcAg
Core/Capsid antigen
- Marker of viral replication
HBV structure: HBeAg
Antigen b/w nucleocapsid & lipid envelope
- Marker of viral replication
HBV Life cycle: 5 big steps
- Entry into hepatocytes
- Transcription
- Translation
- Packaging
- Secretion/Recycling
HBV Life cycle: Entry into hepatocytes (which transporter?)
- Via NTCP transporter
- Uncoat the nucleocapsid
- Genome released into the nucleus
HBV Life cycle: Transcription
- Relaxed circular HBV genome repaired
- Forms covalently closed circular DNA (cccDNA)
HBV Life cycle: what is cccDNA?
Covalently closed circular DNA
- Template for the viral mRNA transcription
- Resulting DNA does not integrate; only serves as an episomal template
HBV Life cycle: translation
- Pregenomic(pg) HBV mRNAs are translated into L/M/S surface, precore, core, polymerase, HBx proteins
HBV Life cycle: packaging
pgRNA and pol are encapsidated into the nucleocapsid
- Viral DNA is reverse-transcribed into partially double stranded DNA (+)
HBV Life cycle: secretion/recycling
- Assembled HBV virions secreted
- Recycled back to the nucleus for amplification of cccDNA
- Secrete hepatitis core & envelop antigens to promote immune tolerance
Phases of chronic HBV infection (4)
- Immune tolerance phase
- Immune active/clearance phase
- Immune inactive/control phase
- Reactivation phase
Immune tolerance phase:
- Labs, liver histology, tx indication
- Labs: HBsAg(+), HBeAg(+), HB DNA >200,000 IU/mL, ALT normal
- Liver: minimal inflammation/fibrosis
- No
Immune active/clearance phase:
- Labs, liver histology, tx indication
- Labs: HBsAg(+), HBeAg(+), HBV DNA >20,000, ALT >2xULN
- Liver: progressive inflammation/fibrosis (nodules)
- Yes
Immune inactive/control phase:
- Labs, liver histology, tx indication
- Labs: HBsAg(+), seroconversion to HBeAg(-)/anti-HBe(+), HBV DNA <2,000 IU/mL, ALT normal
- Liver: minimal inflammation, fibrosis variable
- No; up to 80% of pts remain in this phase long-term
Reactivation phase:
- Labs, liver histology, tx indication
- Labs: HBsAg(+), HBeAg(-)/anti-HBe(+), HBV DNA >2,000 IU/mL, ALT >2xULN
- Liver: progressive inflammation/fibrosis
- Yes
HBV Pharmacology FDA approved
- Interferon Alpha (IFNa)
- Nucleos(t)ide Analogs
HBV IFNa signaling pathway
- JAKs cross-phosphorylate each other on tyrosines (dimerization)
- Activated JAKs phosphorylate receptors on tyrosines
- STATs dock on phosphotyrosines & JAKs phosphorylate them
- STATs dissociate from receptor and dimerize
- Move into the nucleus for gene transcription
HBV IFNa MoA
- ____ of NK cell
- ____ of viral cccDNA
- ____ of the pool of cccDNA
- ____ of the viral nicleocapsid
Innate immunity cytokine that induces gene expression via JAK-STAT signaling that involves:
- Activation of NK cell activity
- Repression of transcription of viral cccDNA
- Partial degradation of the pool of cccDNA
- Destabilization of the viral nucleocapsid
HBV Nucleoside/tide Analogs MoA
- Potent inhibitors of the reverse transcriptase activity of the HBV pol
- Incorporated into the growing DNA chain leading to chain termination and decreasing the amount of viral DNA
HBV nucleosides vs nucleotide
- Nucleoside: sugar, base
- Nucleotide: sugar, base, phosphate
HBV L-Conformation nucleosides
Direct chain terminator
- Lamivudine: high resistance
- Telbivudine
HBV D-Cyclopentane Sugar/nucleoside drug & MoA
Entecavir
- Deoxyguanosine analog: competitive inhibitor (Not a direct inhibitor)
- Inhibits HBV pol/reverse transcriptase
1. Base priming
2. Reverse transcription of (-) strand from the pgmRNA
3. Synthesis of (+) HBV DNA
- Most potent inhibitor
HBV Acyclic phosphnates/nucleotides
- Adefovir: prodrug for acyclic 2’-deoxyAMP (diphosphate active form), undergoes de-esterification, direct chain terminator
- Tenofovir: MoA similar but preferred due to more favorable safety and resistance
HBV Tx goals: HBeAg(+) vs HBeAg(-)
- HBeAg(+): HBeAg seroconversion, loss of serum HBV DNA, normalization of ALT, loss of serum HBsAg
- HBeAg(-): same except HBeAg seroconversion
HBV Peg IFNa (+), (-)
- (+): finite tx course (48 weeks), no resistance
- (-): more AEs, cannot administer to pt with decompensated cirrhosis
HBV Nucleoside/tide analogues (NAs) (+), (-)
- (+): oral dosing, fewer AEs, pts with decompensated cirrhosis qualify for tx
- (-): viral resistance, require indefinite tx, severe ALT flare upon discontinuation
HBV IFNa monotherapy BBW
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders
HBV Peg IFNa AEs
- Hepatic decompensation in pts with compensated cirrhosis
- Flu-like symptoms when starting tx
- Psychiatric: depression, aggressive behavior, psychosis, hallucinations, suicidal ideation
- Anemia, neutropenia, lymphopenia
- Autoimmunity
- Retinopathy
- Stroke
- Dyspnea, pneumonia
- UC, ischemic colitis
- Pancreatitis
- Growth retardation in pts 5-17 yrs
HBV Peg IFNa absolute C/I
- Decompensated cirrhosis
- Pregnancy
- Hx of severe depression or schizophrenia
- Uncontrolled epilepsy
- Uncontrolled autoimmune disease
- HF or COPD
- Retinal disease
HBV Peg IFNa recommended dose & dose adjustments
- Recommended: 48 weeks, should NOT exceed 96 weeks
- Adjustment: neutropenia (ANC <1,000) or thrombocytopenia (PLT <50,000), CrCL <30, moderate or severe depression
HBV Nucleoside/tide analogues (NAs) preferred agents
- Nucleoside: Entecavir
- Nucleotide: TAF > TDF
HBV Entecavir AEs
Elevated glucose, lipase, liver enzymes, creatinine
HBV TDF vs TAF: AEs, DDIs
- TDF: renal dysfunction, decreased bone mineral density
- TAF: less renal and bone toxicity => first-line, DDI: Pgp inducers (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, St. John’s wort)
HCV route of infection
Parenteral, sexual
HCV structure
- Positive-sense, single-stranded RNA
- Untranslated regions at each end (5’UTR), Structural proteins (Core/Capsid & Envelope E1,E2), Nonstructural (NS) proteins
HCV NS proteins: NS1
Viroporin and assembly factor
HCV NS proteins: NS2
Transmembrane protein with Cys-protease activity
HCV NS proteins: NS3/4A dimer
Serine protease (cleave precursor polyprotein into structural/nonstructural proteins) and cofactor
HCV NS proteins: NS4B
Replication complex that anchors to host ER and induces morphological changes in the ER forming a membranous web structure
HCV NS proteins: NS5A
Viral replication and assembly, will bind to host ER
HCV NS proteins: NS5B
RNA-dependent RNA polymerase
HCV Life cycle 9 steps
- Receptor binding
- Endocytosis
- Fusion and uncoating: fusion of endosome and viral envelope, acidification of endosome, release of +sense ssRNA
- RNA translation: host ER translates a single protein with 3000+ AA
- Cleavage: proteolysis by NS3/4A
- Membranous web formation: NS4B, conceal viral replication from pattern recognition receptors (PRRs) in the cytoplasm that could trigger host cell immune activation
- Transcription: (-) RNA template for new +strand viral genome
- Assembly
- Budding/Release: VLDL secretion
HCV entry into the cell
NPC1L1, SR-B1, occludins, claudins
HCV MoA of drugs
- Immune system boost: Peg IFNa, Ribavirin
- Direct-Acting antivirals (DAA): protease/replicase/polymerase inhibitors
HCV Peg IFNa MoA
Innate immunity cytokine that activates JAK-STAT signal transduction, nuclear translocation, gene transactivation
- Degrade HCV viral RNA
- Block HCV RNA translation
- Induce mutations during HCV RNA replication
- Interfere with HCV viral assembly/release
HCV Ribavirin is a synthetic ____ analog and are _______ by host enzymes
Guanosine (purine), phosphorylated
HCV Ribavirin MoA
- Competitively inhibit cellular IMP dehydrogenase & interferes with the synthesis of GTP and nucleic acids (translation)
- Competitively inhibits GTP-dependent 5’ capping of viral mRNA
- Induce differentiation of activated CD4+ T cells from Th-2 to Th-1
- Restore IFNa responsiveness
HCV Protease inhibitors: drugs, MoA
- ‘-previr’
- Potent inhibition of the HCV NS3/4A serine protease -> prevent processing the HCV polyprotein into constituent proteins
HCV Replicase inhibitors: drugs, MoA, 2 forms when existing
- ‘-asvir’
- Inhibit NS5A viral RNA replication and virion assembly
- Unphosphorylated: replication mode, phosphorylated: particle assembly mode (recruitment of lipid droplets)
HCV Polymerase inhibitors: drugs, MoA
- ‘-buvir’
- Inhibit the NS5B RNA-dependent RNA polymerase by binding the catalytic site of the HCV pol or near the active site of the enzyme
HCV Sofosbuvir activity
- Prodrug uptake by hepatocyte
- Carboxylesterase cleave off and reveal hidden phosphate
- Adds two more phosphates = active
- Inhibit NS5B polymerase
- Dephosphorylation/inactivation
HCV Child-Pugh Scoring System
- Clinical scoring system
- A: 5-6 points, compensated
- B: 7-9 points, decompensated
- C: 10-15 points, decompensated
HCV Metavir Scoring System
- Liver biopsy
- F1: portal fibrosis
- F2: portal fibrosis with few septa
- F3: septal fibrosis
- F4: cirrhosis
HCV testing criteria
- Born 1945-1965
- Hx of IV Drug Abuse (IVDA)
- Hx of incarceration
- Tattoo in unregulated setting
- Clotting factor concentrate prior to 1987
- Blood transfusion or solid organ transplant prior to 1992 or from an HCV+ donor
- Long-term hemodialysis
- Exposure to HCV-infected blood
- HIV+
- Unexplained S/S of CLD (ALT)
- Born to HCV+ mother
HCV Ribavirin (RBV) BBW
- Monotherapy not effective for chronic HCV -> combination with IFNa or DAA
- C/I in CD due to toxicity leading to hemolytic anemia
- C/I in pregnancy, 6 months post tx follow-up, contraception must be utilized during tx & post tx
HCV RBV C/I
- Pregnancy
- Autoimmune hepatitis
- Hemoglobinopathies
- CrCl <50 mL/min
- Concomitant use of didanosine (HIV+)
HCV RBV AEs
- Flu-like symptoms on start
- Psychiatric: depression, relapse, aggressive behavior, psychosis, hallucinations, suicidal/homicidal ideation
- CV: HTN, chest pain, supraventricular arrhythmias, acute MI
- Hemolytic anemia
HCV DAAs: prior use, preferred agents
- All pts should be tested for HBV coinfection prior to starting tx
- Epclusa (NS5B pol & NS5A inhibitor)
- Mavyret (Protease & NS5A inhibitor)
- Harvoni (NS5A & NS5B inhibitor)
HCV Epclusa w or w/o compensated cirrhosis: genotype, dose, duration
- All genotypes 1-6
- 1 T po QD
- 12 weeks
HCV Epclusa AEs, DDIs
- AEs: well-tolerated
- DDIs: Pgp and BRCP inducers (rifampin, St. John’s wort, carbamazepine), CYP2B6 inducers
HCV Mavyret treatment-naive, w or w/o compensated cirrhosis: genotype, dose, duration
- All genotypes 1-6
- 3 T po QD
- 8 weeks
HCV Mavyret AEs, DDIs
- well tolerated
- Strong CYP3A4 inducers (carbamazepine, efavirenz, St. John’s wort)
HCV Harvoni AEs, DDIs
- Well tolerated
- Strong Pgp inducers (carbamazepine, phenytoin, phenobarbital, rifampin, rifabutin, St. John’s wort)
- H2RAs, PPIs, antacids decrease absorption
- Amiodarone: severe bradycardia
- Digoxin: toxicity
- Rosuvastatin: rhabdomyolysis
HCV preferred regimens for tx-naive : G1a
- No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks
- Mavyret 8 wks
- Harvoni 12 wks
-Same
HCV preferred regimens for tx-naive : G1b
- No cirrhosis vs compensated cirrhosis
- Epclusa 8 wks (No cirrhosis), 12 wks (cirrhosis)
- Mavyret 8 wks
- Harvoni 12 wks
- Zepatier 12 wks
HCV preferred regimens for tx-naive : G2
- No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks
- Mavyret 8 wks
Same
HCV preferred regimens for tx-naive : G3
- No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks
- Mavyret 8 wks
Same
HCV preferred regimens for tx-naive : G4
- No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks
- Mavyret 8 wks
- Harvoni 12 wks
- Zepatier 12 wks
Same
HCV preferred regimens for tx-naive : G5 or 6
- No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks
- Mavyret 8 wks
- Harvoni 12 wks
Same
HCV preferred regimens for decompensated cirrhosis: No RBV C/I
- Epclusa/Harvoni + low-dose RBV (600mg/d increased as tolerated to goal of 1000mg/d) for 12 wks
- G3: only Epclusa + RBV (no Harvoni)
HCV preferred regimens for decompensated cirrhosis: RBV C/I
Epclusa or Harvoni 24 weeks
Metabolic functions of liver
- CHO, protein, hormone metabolism
- Synthesis of fatty acids, lipoproteins, cholesterol, plasma proteins, urea
- RBC production
- Ketogenesis
Storage functions of liver
Glycogen, ADEK/B12 vitamins, iron, copper
Excretory/Secretory functions of liver
Bile, IGF-1, most blood proteins, cholesterol, fatty acids
Protective functions of liver
- Purification, transformation, clearance: endo/exogenous
- Kupffer cell: bacteria, foreign materials
Circulatory function of liver
Antechamber of the heart: collect portal blood from the GI tract
Coagulation function of liver
Fibrinogen I, prothrombin II, factors V, VII, IX, X, XI, protein C/S, antithrombin
Liver enzymes
- Transaminases (hepatocytes): AST, ALT
- Cholestatic enzymes (epithelial): ALP, GGT
Liver: bile vs blood flow
- Bile: central to portal triad to portal circulation
- Blood: portal triad to portal vein to hepatic artery to hepatocytes to central
Acute vs Chronic hepatitis characteristics
- Acute: inflammatory infiltrate, MP aggregates
- Chronic: fibrosis
What is MASH?
- Metabolic dysfunction-associated with steatohepatitis
- Non-alcoholic fatty liver disease
Characteristics of MASH & ASH
- Macrovesicular steatosis + inflammation
- Infiltration of both lymphocytes and Kupffer cells
- Ballooned hepatocytes that also contain Mallory-Denk bodies
- Perivenular/cellular “chicken wire” fibrosis
Liver lipid homeostasis to increase fat
- De novo fatty acid synthesis
- Long chain FFA uptake transporter
Two-hit or multi-hit theory of MASH
- First hit: fat accumulation in the liver (obesity, long-term fasting)
- Second hit: injury leads to inflammation (drugs, pathogens, leaky gut, genetic abnormalities, oxidative stress)
What is AUD?
- Alcohol Use Disorder
- ASH: alcoholic steatohepatitis
AUD/ASH pathophysiology
- Hepatic fat storage
- Inflammation: trigger Kupffer cell and leakage
- Oxidation: CYP2E1
- ER stress: ethanol-mediated, protein mis-folding
Mechanism of AUD/ASH inflammation
- Alcohol intake leads to activation of innate & adaptive immunity
- Leads to inflammation and fibrosis
Cirrhosis induced by MASH
¼ of pts never develop cirrhosis and straight to HCC
Treatment for MASH/ASH
- Reduce weight
- Lifestyle modification: exercise, diet
- Reduce or no ethanol
- Avoid drugs or toxins with liver injury
- Avoid pathogens or drugs with gut injury
- No FDA approved drug
Cirrhosis: HVPG >10 to 12 indicates
Clinically significant portal HTN: formation of varices, high risk of progression to decompensation & HCC
Cir: HVPG >12 indicates
Decompensation: high risk of variceal bleeding, formation of ascites
Cir: lab results
- Low: BUN, albumin, RBC, WBC, Plts
- High: ammonia
Cir: management
- Definitive: only liver transplantation
- Supportive care
Cir: prognosis stages 1-5
- Compensated with no varices
- Compensated with varices
- Decompensated with ascites
- Decompensated with GI bleeds
- Infection or renal failure
Cir: what are ascites?
Increased portal venous pressure (water out) and decreased plasma oncotic pressure (water in)
Cir: drugs to avoid in ascites
- Nonselective beta blockers should be stopped in pts with advanced cirrhosis/progressively declining BP (refractory ascites)
- ACEi, ARBs, NSAIDs, nephrotoxic drugs
Cir: What indicates Spontaneous Bacterial Peritonitis (SBP)?
Ascitic fluid neutrophil count (ANC) >250/mm3
Cir: primary prophylaxis of SBP use vs avoid
- Bactrim or Ciprofloxacin
- Avoid PPIs (increase risk of SBP and C. diff)
Cir: tx of SBP
- Ceftriaxone IV x5 days
- Albumin
Cir: Secondary prophylaxis of SBP
Bactrim or Ciprofloxacin
Cir: diuretic tx for ascites
- Must be added if Na excretion =< 50 mEq/day
- Na >30: spironolactone
- Na 10-30: spironolactone + furosemide (100:40 ratio)
- Na <10: refractory, so other options LVP, TIPS
Cir: risk factors for variceal bleeding
- HVPG >12 mmHg
- Medium-large varices, small varices with red wale signs
Cir: primary prevention of medium-large varices & absolute C/I
- Nonselective beta blocker: propranolol, nadolol, carvedilol
- Endoscopic variceal ligation (EVL): 2nd line for refractory pts or who cannot take nonselective bb
- COPD, CHF
Cir: primary prevention of small varices with red wale signs
Nonselective beta blocker: propranolol, nadolol, carvedilol
Cir: tx of active variceal bleeding
- Oxygenation and hemodynamic stability
- NG tube: antibiotic for SBP prophylaxis
- Octreotide 3-5 days
- EVL combo more effective
Cir: variceal rebleeding or high rebleeding risk pts management
Rescue TIPS: lowers portal pressure by shunting blood from portal vein directly into hepatic vein
Cir: secondary prevention of variceal bleeding mangement
- Nonselective bb + EVL
- TIPS if refractory: bridging therapy for good liver transplant candidates
Cir: what is the cause of hepatic encephalopathy
- Ammonia produced by intestinal bacteria that breaks down blood or urea
- Systemic absorption is pH dependent
- At low pH, NH3 gets ionized to NH4+ -> not able to cross membrane easily -> not absorbed efficiency -> :) !!!
Cir: hepatic encephalopathy tx
- Nutrition
- Lactulose: non-absorbable disaccharide converted to lactic/formic/acetic acid by gut bacteria, so lowers pH (dose= 30-50 mL PO Q2-3H titrated to 3-4 loose stools daily)
- Rifaximin: antibiotic that inhibits growth of ammonia-producing gut bacteria
