Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

GI/Hepatic > Exam 2 > Flashcards

Exam 2 Flashcards

(142 cards)

Start Studying
1
Q

(G) Pancreatitis: Endocrine function

A

Glucose homeostasis regulation
- Beta cells (insulin), alpha cells (glucagon), D cells (somatostatin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

(G) Pancreatitis: Exocrine function

A

Acinar cells: digestive enzymes (lipases, carbohydrase, peptidase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

(G) What is acute pancreatitis?

A

Painful episodic inflammation
- may lead to chronic pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

(G) What is chronic pancreatitis?

A

Inflammatory condition affecting the pancreas and involves progressive, irreversible damage to the pancreatic tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

(G) Chronic pancreatitis results in ___, ____, and ____

A

Loss of glandular function (endo/exo), fat malabsorption (steatorrhea), and protein maldigestion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

(G) CP treatment: loss of function

A

Pancreatic enzymes (lipase, amylase, and proteases) insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

(G) CP treatment: pain

A

Delivery of active proteases to the duodenum to repress CCK secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

(St) What causes acute pancreatitis (AP)?

A
  • Gallstones
  • Chronic alcohol abuse
  • Pancreatic cancer
  • Hypertriglyceridemia
  • Drugs (rare)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

(St) S/S, lab tests of AP

A
  • Abrupt onset of severe persistent epigastric or LUQ pain that typically radiates to back
  • N/V
  • Voluntary guarding
  • Elevated amylase and lipase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

(St) How is AP diagnosed?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

(St) Characteristic findings on CECT or MRI with AP (2 types of AP)

A
  • Interstitial edematous AP: focal or diffuse pancreatic edema
  • Necrotizing AP: focal or diffuse areas of pancreatic necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

(St) Severity of AP: Mild
- Characteristics
- Local complications

A
  • No organ failure
  • No local complications
  • Generally marked improvement ( & return to oral feeding) w/i 48 hrs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

(St) Severity of AP: Moderately Severe
- Characteristics
- Local complications

A
  • Local complications &/or transient organ failure (<48 hrs)
  • Fluid collections, pseudocysts, sterile/infected necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

(St) Severity of AP: Severe
- Characteristics
- Local complications

A
  • Persistent organ failure (> 48 hrs)
  • Early severe (=< 7 d): SIRS &/or organ failure, GI bleed, serum Cr >=2
  • Late severe (> 7 d): sepsis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

(St) Severity of AP: Determine SIRS criteria

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

(St) Indications of ICU admissions for AP

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

(St) Treating ICU AP patients (4)

A
  1. Early aggressive hydration: 0.9% NS or lactated Ringer’s over 12-24 hrs
  2. Pain management: IV opioids hydromorphone or morphine (PCA > IVP)
  3. Nutrition
  4. IV antibiotics: empiric antibiotics indicated with necrotizing pancreatitis showing systemic signs of infection (fever, leukocytosis, organ dysfunction)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

(St) Treating ICU AP patients:
- Nutrition for mild AP

A
  • Oral intake typically resumes in 3-7 days
  • Can start with clear liquids or solid low-fat diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

(St) Treating ICU AP patients:
- Nutrition for moderately severe to severe AP

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

(St) Treating ICU AP patients:
- Antibiotics: gram negative bacteria

A
  • Carbipenem
  • Fluoroquinolone + Metronidazole
  • 3rd/4th gen Cephalosporin + Metronidazole
  • Pip/Tazo (Zosyn)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

(St) Treating ICU AP patients:
- Antibiotics: gram positive bacteria

A

Vancomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

(St) Potential etiologies of fever and relapsing AP

A
  • Pancreatic abscess or necrosis
  • Infected pseudocyst
  • Nosocomial pneumonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

(St) High neutrophils (segs, bands) indicate higher chance of ____

A

Bacterial

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

(St) High lymphocytes indicate higher chance of ____

A

Viral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
(St) Causes of Chronic Pancreatitis (CP)
- **Chronic alcohol abuse** - CF, pancreatic cancer, hypertriglyceridema
26
(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
27
(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
28
(St) Management of CP (3)
1. Chronic pain management: eliminate contributing factor -> APAP or NSAID -> opioid 2. Dietary fat restriction: small, frequent meals, medium chain TG 3. Pancreatic enzyme supplements
29
(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
30
HBV vs HCV - DNA/RNA, manageable/curable
- HBV: DNA, manageable - HCV: RNA, curable
31
HBV routes of infection
Parenteral, sexual, perinatal
32
HBV Physical exam
- Icteric sclera, skin, secretions - Decreased bowel sounds, increased abdominal girth - Asterixis - Spider angiomas
33
HBV Pathology
- Nodules of damaged & regenerating hepatocytes - Fibrous bands > cirrhosis > HCC - Ground-glass cytoplasm (light) - Bile pigment accumulation (dark)
34
HBV structure: HBsAg
Surface antigen - Most abundant antigens - Detectable at onset of clinical symptoms
35
HBV structure: HBcAg
Core/Capsid antigen - Marker of viral replication
36
HBV structure: HBeAg
Antigen b/w nucleocapsid & lipid envelope - Marker of viral replication
37
HBV Life cycle: 5 big steps
1. Entry into hepatocytes 2. Transcription 3. Translation 4. Packaging 5. Secretion/Recycling
38
HBV Life cycle: Entry into hepatocytes (which transporter?)
- Via **NTCP** transporter - Uncoat the nucleocapsid - Genome released into the nucleus
39
HBV Life cycle: Transcription
- Relaxed circular HBV genome repaired - Forms covalently closed circular DNA (cccDNA)
40
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
41
HBV Life cycle: translation
- Pregenomic(pg) HBV mRNAs are translated into L/M/S surface, precore, core, polymerase, HBx proteins
42
HBV Life cycle: packaging
pgRNA and pol are **encapsidated** into the **nucleocapsid** - Viral DNA is **reverse-transcribed** into partially double stranded DNA (+)
43
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
44
Phases of chronic HBV infection (4)
1. Immune tolerance phase 2. Immune active/clearance phase 3. Immune inactive/control phase 4. Reactivation phase
45
Immune tolerance phase: - Labs, liver histology, tx indication
- Labs: HBsAg(+), HBeAg(+), HB DNA >200,000 IU/mL, ALT normal - Liver: minimal inflammation/fibrosis - No
46
Immune active/clearance phase: - Labs, liver histology, tx indication
- Labs: HBsAg(+), HBeAg(+), HBV DNA >20,000, ALT >2xULN - Liver: progressive inflammation/fibrosis (nodules) - Yes
47
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
48
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
49
HBV Pharmacology FDA approved
- Interferon Alpha (IFNa) - Nucleos(t)ide Analogs
50
HBV IFNa signaling pathway
1. JAKs cross-phosphorylate each other on tyrosines (dimerization) 2. Activated JAKs phosphorylate receptors on tyrosines 3. STATs dock on phosphotyrosines & JAKs phosphorylate them 4. STATs dissociate from receptor and dimerize 5. Move into the nucleus for gene transcription
51
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
52
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**
53
HBV nucleosides vs nucleotide
- Nucleoside: sugar, base - Nucleotide: sugar, base, phosphate
54
HBV L-Conformation nucleosides
Direct chain terminator - Lamivudine: high resistance - Telbivudine
55
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
56
HBV Acyclic phosphnates/nucleotides
1. Adefovir: prodrug for acyclic 2'-deoxyAMP (diphosphate active form), undergoes de-esterification, direct chain terminator 2. Tenofovir: MoA similar but preferred due to more favorable safety and resistance
57
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
58
HBV Peg IFNa (+), (-)
- (+): finite tx course (48 weeks), no resistance - (-): more AEs, cannot administer to pt with decompensated cirrhosis
59
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
60
HBV IFNa monotherapy BBW
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders
61
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
62
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
63
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
64
HBV Nucleoside/tide analogues (NAs) preferred agents
- Nucleoside: Entecavir - Nucleotide: TAF > TDF
65
HBV Entecavir AEs
Elevated glucose, lipase, liver enzymes, creatinine
66
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)
67
HCV route of infection
Parenteral, sexual
68
HCV structure
- Positive-sense, single-stranded RNA - Untranslated regions at each end (5'UTR), Structural proteins (Core/Capsid & Envelope E1,E2), Nonstructural (NS) proteins
69
HCV NS proteins: NS1
Viroporin and assembly factor
70
HCV NS proteins: NS2
Transmembrane protein with Cys-protease activity
71
HCV NS proteins: NS3/4A dimer
Serine protease (cleave precursor polyprotein into structural/nonstructural proteins) and cofactor
72
HCV NS proteins: NS4B
Replication complex that anchors to host ER and induces morphological changes in the ER forming a membranous web structure
73
HCV NS proteins: NS5A
Viral replication and assembly, will bind to host ER
74
HCV NS proteins: NS5B
RNA-dependent RNA polymerase
75
HCV Life cycle 9 steps
1. Receptor binding 2. Endocytosis 3. Fusion and uncoating: fusion of endosome and viral envelope, acidification of endosome, release of +sense ssRNA 4. RNA translation: host ER translates a single protein with 3000+ AA 5. Cleavage: proteolysis by NS3/4A 6. Membranous web formation: NS4B, conceal viral replication from pattern recognition receptors (PRRs) in the cytoplasm that could trigger host cell immune activation 7. Transcription: (-) RNA template for new +strand viral genome 8. Assembly 9. Budding/Release: VLDL secretion
76
HCV entry into the cell
NPC1L1, SR-B1, occludins, claudins
77
HCV MoA of drugs
1. Immune system boost: Peg IFNa, Ribavirin 2. Direct-Acting antivirals (DAA): protease/replicase/polymerase inhibitors
78
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
79
HCV Ribavirin is a synthetic ____ analog and are _______ by host enzymes
Guanosine (purine), phosphorylated
80
HCV Ribavirin MoA
1. Competitively inhibit cellular IMP dehydrogenase & interferes with the synthesis of GTP and nucleic acids (translation) 2. Competitively inhibits GTP-dependent 5' capping of viral mRNA 3. Induce differentiation of activated CD4+ T cells from Th-2 to Th-1 4. Restore IFNa responsiveness
81
HCV Protease inhibitors: drugs, MoA
- '-previr' - Potent inhibition of the HCV NS3/4A serine protease -> prevent processing the HCV polyprotein into constituent proteins
82
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)
83
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
84
HCV Sofosbuvir activity
- Prodrug uptake by hepatocyte - Carboxylesterase cleave off and reveal hidden phosphate - Adds two more phosphates = active - Inhibit NS5B polymerase - Dephosphorylation/inactivation
85
HCV Child-Pugh Scoring System
- Clinical scoring system - A: 5-6 points, compensated - B: 7-9 points, decompensated - C: 10-15 points, decompensated
86
HCV Metavir Scoring System
- Liver biopsy - F1: portal fibrosis - F2: portal fibrosis with few septa - F3: septal fibrosis - F4: cirrhosis
87
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
88
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
89
HCV RBV C/I
- Pregnancy - Autoimmune hepatitis - Hemoglobinopathies - CrCl <50 mL/min - Concomitant use of didanosine (HIV+)
90
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
91
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)
92
HCV Epclusa w or w/o compensated cirrhosis: genotype, dose, duration
- All genotypes 1-6 - 1 T po QD - 12 weeks
93
HCV Epclusa AEs, DDIs
- AEs: well-tolerated - DDIs: Pgp and BRCP inducers (rifampin, St. John's wort, carbamazepine), CYP2B6 inducers
94
HCV Mavyret treatment-naive, w or w/o compensated cirrhosis: genotype, dose, duration
- All genotypes 1-6 - 3 T po QD - 8 weeks
95
HCV Mavyret AEs, DDIs
- well tolerated - Strong CYP3A4 inducers (carbamazepine, efavirenz, St. John's wort)
96
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
97
HCV preferred regimens for tx-naive : G1a - No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks - Mavyret 8 wks - Harvoni 12 wks -Same
98
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
99
HCV preferred regimens for tx-naive : G2 - No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks - Mavyret 8 wks Same
100
HCV preferred regimens for tx-naive : G3 - No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks - Mavyret 8 wks Same
101
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
102
HCV preferred regimens for tx-naive : G5 or 6 - No cirrhosis vs compensated cirrhosis
- Epclusa 12 wks - Mavyret 8 wks - Harvoni 12 wks Same
103
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)
104
HCV preferred regimens for decompensated cirrhosis: RBV C/I
Epclusa or Harvoni 24 weeks
105
Metabolic functions of liver
- CHO, protein, hormone metabolism - Synthesis of fatty acids, lipoproteins, cholesterol, plasma proteins, urea - RBC production - Ketogenesis
106
Storage functions of liver
Glycogen, ADEK/B12 vitamins, iron, copper
107
Excretory/Secretory functions of liver
Bile, IGF-1, most blood proteins, cholesterol, fatty acids
108
Protective functions of liver
- Purification, transformation, clearance: endo/exogenous - Kupffer cell: bacteria, foreign materials
109
Circulatory function of liver
Antechamber of the heart: collect portal blood from the GI tract
110
Coagulation function of liver
Fibrinogen I, prothrombin II, factors V, VII, IX, X, XI, protein C/S, antithrombin
111
Liver enzymes
- Transaminases (hepatocytes): AST, ALT - Cholestatic enzymes (epithelial): ALP, GGT
112
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
113
Acute vs Chronic hepatitis characteristics
- Acute: inflammatory infiltrate, MP aggregates - Chronic: fibrosis
114
What is MASH?
- Metabolic dysfunction-associated with steatohepatitis - Non-alcoholic fatty liver disease
115
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
116
Liver lipid homeostasis to increase fat
1. De novo fatty acid synthesis 2. Long chain FFA uptake transporter
117
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)
118
What is AUD?
- Alcohol Use Disorder - ASH: alcoholic steatohepatitis
119
AUD/ASH pathophysiology
- Hepatic fat storage - Inflammation: trigger Kupffer cell and leakage - Oxidation: CYP2E1 - ER stress: ethanol-mediated, protein mis-folding
120
Mechanism of AUD/ASH inflammation
- Alcohol intake leads to activation of innate & adaptive immunity - Leads to inflammation and fibrosis
121
Cirrhosis induced by MASH
¼ of pts never develop cirrhosis and straight to HCC
122
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
123
Cirrhosis: HVPG >10 to 12 indicates
Clinically significant portal HTN: formation of varices, high risk of progression to decompensation & HCC
124
Cir: HVPG >12 indicates
Decompensation: high risk of **variceal bleeding**, formation of ascites
125
Cir: lab results
- Low: BUN, albumin, RBC, WBC, Plts - High: ammonia
126
Cir: management
- Definitive: **only** liver transplantation - Supportive care
127
Cir: prognosis stages 1-5
1. Compensated with no varices 2. Compensated with varices 3. Decompensated with ascites 4. Decompensated with GI bleeds 5. Infection or renal failure
128
Cir: what are ascites?
Increased portal venous pressure (water out) and decreased plasma oncotic pressure (water in)
129
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
130
Cir: What indicates Spontaneous Bacterial Peritonitis (SBP)?
Ascitic fluid neutrophil count (ANC) >250/mm3
131
Cir: primary prophylaxis of SBP use vs avoid
- Bactrim or Ciprofloxacin - Avoid PPIs (increase risk of SBP and C. diff)
132
Cir: tx of SBP
- Ceftriaxone IV x5 days - Albumin
133
Cir: Secondary prophylaxis of SBP
Bactrim or Ciprofloxacin
134
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
135
Cir: risk factors for variceal bleeding
- **HVPG >12 mmHg** - Medium-large varices, small varices with red wale signs
136
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
137
Cir: primary prevention of small varices with red wale signs
Nonselective beta blocker: **propranolol, nadolol, carvedilol**
138
Cir: tx of active variceal bleeding
1. Oxygenation and hemodynamic stability 2. NG tube: antibiotic for SBP prophylaxis 3. Octreotide 3-5 days 4. EVL combo more effective
139
Cir: variceal rebleeding or high rebleeding risk pts management
Rescue TIPS: lowers portal pressure by shunting blood from portal vein directly into hepatic vein
140
Cir: secondary prevention of variceal bleeding mangement
- Nonselective bb + EVL - TIPS if refractory: bridging therapy for good liver transplant candidates
141
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 -> :) !!!
142
Cir: hepatic encephalopathy tx
1. Nutrition 2. 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) 3. Rifaximin: antibiotic that inhibits growth of ammonia-producing gut bacteria

GI/Hepatic (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions