T5 - IE5 - Gastroenterology - Lam - Portal Hypertension & Complications of the Liver

Cirrhosis is the _______ ______ of any chronic liver disease

- end stage (of any chronic liver disease)

Cirrhosis is the end stage of any __________ __________ ________

- (of any) chronic liver disease

Cirrhosis is characterized histologically by __________ _________ surrounded by _______ tissue

- regenerative nodules

- fibrous (tissue)

Cirrhosis example figure

Clinical Types of Cirrhosis

Compensated

Decompensated

Cirrhosis - Burden of Disease: a ________ ______ of morbidity and mortality in the United States

- leading cause (of morbidity and mortality)

Early readmission increase clinical / economic burden in such patients

Cirrhosis - Burden of Disease: Early readmission increase ________ / __________ burden in such patients

- clinical / economic

Stages and substages of cirrhosis chart

Compensated cirrhosis substages

mild portal hypertension (PH)

clinically significant portal hypertension (CSPH)

No varices

Varices

Decompensated cirrhosis substages

variceal hemorrhage

ascites

hepatic encephalopathy

HE

hepatic encephalopathy

Late (further) decompensation substages

recurrent variceal hemorrhage

refractory ascites, hyponatremia, hepatorenal syndrome (HRS)

recurrent hepatic encephalopathy

jaundice

HRS

hepatorenal syndrome

Complications of cirrhosis pathway chart

Clinical presentation of liver disease

weakness, tiredness, malaise

N/V, abdominal discomfort and pain

anorexia, weight loss (common with acute and chronic liver disease)

jaundice or dark urine

sudden and massive bleeding, with or without shock on presentation

edema and abdominal swelling (ascites); splenomegaly

Clinical presentation of liver disease: _________ _____ is common with chronic and acute liver disease

- weight loss (is common)

Portal hypertension - epidemiology: Portal hypertension (HTN) is a frequent manifestation of ______ ________

- (frequent manifestation of) liver cirrhosis

Portal hypertension - epidemiology: 2016 liver cirrhosis accounted for ~40,545 deaths, making it the _____ leading cause of US deaths

Western countries: ________ and _____ cirrhosis are the leading causes of portal HTN & esophageal varices

- 10th (leading cause of US deaths)

- alcoholic

- viral (cirrhosis)

Portal hypertension - epidemiology in western countries: alcoholic and viral cirrhosis are the leading causes of ____________ ____ and ___________ ______

- (leading causes of) portal HTN

- esophageal varices

Portal hypertension - epidemiology: males make up more than _____% of patients with chronic liver disease and cirrhosis

- 60(% of patients with chronic liver disease and cirrhosis)

Portal HTN: _________ pressures in the portal venous system, a major vein that _______ to the liver that ___ ___ mm Hg

- elevated (pressures)

- leads (to the liver)

- ≥ 10 (mm Hg)

Decompensated portal hypertension ≥ 12 mm Hg

Portal hypertension: elevated pressures in the ______ _______ system, a major that vein that leads to the _______ that is ≥ 10 mm Hg

Decompensated portal hypertension: ____ ____ mm Hg

- portal venous (system)

- (vein that leads to the) liver

- ≥ 12 (mm Hg)

Portal hypertension is an increase in the pressure within the portal vein caused by ___-________, ______-_______ or ________-_______ factors

- pre-hepatic

- intra-hepatic

- post-hepatic (factors)

Results in increase in pressure (HVPG ≥ 10 mm Hg), results in increase in portal venous flow, or hepatic resistance

Portal hypertension: results in __________ in pressure (HVPG ≥ 10 mm Hg), results in increase in _______ _______ ______, or hepatic _________

- increase (in pressure)

- (increase in) portal venous flow

- (hepatic) resistance

This causes the development of varices across the esophagus and stomach to get around the blockage

Portal hypertension: due to increased in pressure, portal venous flow and hepatic reisstance

Results in development of _______ across the esophagus and stomach to get around the __________

- (development of) varices

- (to get around the) blockage

Portal Hypertension Anatomy

Portal hypertension causes

pre-hepatic (obstruction)

- portal vein thrombosis

- chronic pancreatitis

intra-hepatic (intrinsic)

- liver cirrhosis [most common]

post-hepatic (structural)

- Budd-chiari syndrome

- venous occlusive disease

- cardiac-related (e.g., right heart failure or constrictive [occlusive pericarditis])

Portal hypertension: pre-hepatic causes are usually due to ___________

- (usually due to) obstruction

Portal hypertension: pre-hepatic causes

portal vein thrombosis

chronic pancreatitis

Portal hypertension - intra-hepatic is usually ___________

- (usually) intrinsic

Portal hypertension - intra-hepatic: _________ ___________ is the most common cause of portal HTN

- liver cirrhosis (is the most common cause)

Portal hypertension - intra-hepatic causes

liver cirrhosis (the most common)

Portal hypertension - post-hepatic is due to a _________ cause

- structural (cause)

Portal hypertension - post-hepatic (structural) causes

Budd-Chiari syndrome

Venous occlusive disease

Cardiac-related

(e.g., right heart failure or constrictive [occlusive pericarditis])

Portal-hypertension: intra-hepatic causes compose of ___ ___% of the cases with ___________ being the most common

- ≥ 70(% of the cases)

- cirrhosis (being the most common)

Portal hypertension - intra-hepatic: Causes of Cirrhosis

alcohol (most common)

chronic HBV, HCV

autoimmune hepatitis

PBC (primary biliary cirrhosis)

PSC (primary sclerosingitis)

NASH (non-alcoholic steatohepatitis)

Biliary atresia: occurs in children

Cryptogenic / idiopathic: 20% of all diagnoses

Portal hypertension - intra-hepatic: other causes than cirrhosis

schistosomiasis: occurs world-wide

genetic causes

- Wilson disease

- hemochromatosis

- α1-antitrypsin deficiency

- congenital hepatic fibrosis

Pharmacological treatments & management of portal hypertension figure

Portal hypertension - pharmacological treatments: β-blockers

propranolol (INDERAL)

nadolol (CORGARD)

carvedilol (COREG)

propranolol

INDERAL

nadolol

CORGARD

carvedilol

COREG

Portal hypertension - pharmacological treatments: β-blockers adverse effects

light-headedness

fatigue

hypotension

bradyarhythmia

hyperglycemia

ED

Portal hypertension - pharmacological treatments: β-blockers contraindications

asthma

diabetes with frequent or severe hypoglycemia

peripheral vascular disease

Portal Hypertension Complications Algorithm

increase pressure in peritoneal capillaries

portosystemic shunting of blood

splenomegaly

Ascites is caused by ______________ from decreased _________ __________

- hypoalbuminemia

- (from decreased) protein synthesis

This causes increase in capillary permeability and volume overload, which leads fluids escaping to vascular space and accumulating in peritoneal space (cavity)

Ascites is caused by hypoalbuminemia from decreased protein synthesis

This causes increase in ____________ ________ and volume _________

- (increase in) capillary permeability

- (volume) overload

Which allows fluid to escape vascular space and accumulate in peritoneal space

Ascites causes increase in capillary permeability and volume overload, which allows fluid to __________ the _______ space and _________ in peritoneal cavity

- escape

- vascular (space)

- accumulate (in peritoneal cavity)

Ascites results in the increased _________ _______ in the abdominal ________

- (increased) hydrostatic pressure

- (abdominal) circulation

Fluid is pushed into the peritoneal space ("third spacing")

Ascites: fluid is used into the _________ space (______ _______)

Sinusoidal pressure > _______ _______ pressure

- peritoneal (space)

- "third spacing"

- (sinusoidal pressure >) colloid oncotic (pressure)

Ascites is induced by ____________ ________ and ______

- physiologic stress

- fluids

Ascites figure

Ascites complications

spontaneous bacterial peritonitis

hepatorenal syndrome

Ascites pharmacologic therapy

Diuretics

colloids

Ascites management

sodium / water restriction

large volume paracentesis

peritoneal-venous shunt

Ascites approach: perform ___________, drain the _______ fluids from abdomen into __________

- pericentesis

- excess (fluids)

- (into) vacutainers

Ascites approach: administer _______ (with or without ________)

- diuretics

- (with or without) albumin

Ascites approach: administer _________ to increase the ________ pressure inside the veins and vascular spaces

- (administer) albumin

- (increase the) colloid (pressure)

Causes water to go back into vascular spaces and veins

Ascites approach: administering albumin causes water to go back into the ________ ______ and ______

- vascular spaces

- veins

Ascites approach: monitor _____ _____ and _______

- vital signs

- electrolytes

Ascites pharmacological treatments

spironolactone

furosemide

spironolactone + furosemide (preferred treatment approach)

Ascites pharmacological treatments: spironolocatone is ______ for ascites

- DOC (for ascites)

DOC = drug of choice

Onset of effect: 3-5 days before maximal natriuresis achieved; titrate dose Q3-5 days

Ascites pharmacological treatments: spironolocatone onset of effect ___-___ days before maximal natriuresis achieved, titrate dose ____-____ days

- 3-5 (days)

- (titrate dose) 3-5 (days)

Dose-limiting side effects: acute renal failure

Ascites pharmacological treatments: spironolocatone dose-limiting side effects

acute renal failure

monitor:

- hyperkalemia

- gynecomastia

for spironolactone

Ascites pharmacological treatments: spironolocatone monitor

hyperkalemia

gynecomastia

Ascites pharmacological treatments: furosemide is ____ _______ for ascites as monotherapy

- NOT effective (for ascites as monotherapy)

Ascites pharmacological treatments: spironolactone:furosemide ratio

100mg:40 mg

Ascites pharmacological treatments: ___________ + __________ is the preferred treatment approach

- spironolactone (+) furosemide

Ascites pharmacological treatments: furosemide monitoring

BP

UOP

electrolytes

SCr / BUN

DOC

drug of choice

Ascites treatment: albumin ____ use with large volume ____________

- PRN (use)

- (large volume) paracentesis

> 5 liters removed

Ascites treatment: albumin MOA

expands effective plasma volume and may improve effect of vasopressors (by binding vasoconstrictions and increasing central blood volume)

Ascites monitoring parameters

daily weights (should be losing ~500 mL/day)

electrolytes

SCr / BUN

peripheral edema

Spironolactone

ALDACTONE

Spironolactone (ALDACTONE) is preferred as ________ treatment of ascites

- initial (treatment of ascites)

Furosemide

LASIX

Furosemide (LASIX): IV to PO

IV = 50% of PO dose

Routes: PO, IVP, IV infusion NOT effective as monotherapy for ascites

Albumin infusion rate rate for ascites

1 mL/min

STOP infusion if patient is hypotensive

Ascites - non-pharmacological treatment

Low sodium diet

Fluid restriction

Paracentesis ("tap")

TIPS: transjugular intrahaptic portosystemic shunt

TIPS

transjugular intrahepatic portosystemic shunt

Ascites - non-pharmacological treatment: low sodium diet

< 2 gms of sodium / day

Ascites - non-pharmacological treatment: fluid restriction

< 1000 mL/day

only for symptomatic dilutional hyponatremia (Na+ < 130 mEq/L + ascites and/or edema)

Paracentesis ("tap"): treatment option for ______ volume and _______ ascites

- large (volume)

- refractor (ascites)

Typically Q2-4 weeks in refractory

Paracentesis: has _______ risk of complications; ______ and ______ _______ than conventional diuretic therapy

- lower (risk of complications)

- faster

- more effective (than conventional diuretic therapy)

Paracentesis: larger volume (> 5 liters) tap should be accompanied by _________ to decrease complications

- (accompanied by) albumin

Ascites - non-pharmacological treatment: TIPS - prevent ascites in ________ patients; associated with decreased ___-_________- of ascitic fluid compared to large volume taps

- refractory (patients)

- re-accumulation (of ascitic fluid)

Portal hypertension complications - spider angioma: red ________ with peripherally ___________ out arteries

- (red) macules

- branching (out arteries)

Macules = body of the spider

Arteries = spider legs

Portal hypertension complications - spider angioma: develop because the liver is primarily responsible for ________________ estrogen

Estrogen can cause _________ _________

- metabolizing (estrogen)

- (can cause) spider angiomas

If there are more than 5 of these, there may be something wrong especially if patient is at risk of liver failure

Portal hypertension complications - caput Medusa: tortuous, dilated _________ _________ and another _______ of portal hypertension

- dilated (umbilical vessels)

- sign (of portal hypertension)

Spider angiomas figure

Caput medusae figure

Variceal bleeding: splanchnic system drains venous blood from the _____ _______ to the _______

- (from the) GI tract

- (to the) liver

Portal HTN causes resistance to drainage -> superficial vessels (varices) develop to handle overload

Variceal bleeding: splanchnic system drains venous blood from the GI tract to the liver

Portal HTN causes ___________ to drainage -> superficial vessels (varices) ___________ to handle overload

- resistance (to drainage)

- develop (to handle overload)

Varices are weak & easily damaged, which causes GI bleeding

Portal HTN causes resistance to drainage -> superficial vessels (varices) develop to handle overload

Variceal bleeding: splanchnic system drains venous blood from the GI tract to the liver

___________ ____________ causes resistance to drainage -> ______________ ____________ (___________) develop to handle overload

- portal hypertension

- superficial vessels (varices)

Variceal bleeding: Portal HTN causes resistance to drainage -> superficial vessels (varices) develop to handle overload

Varices are _____ & easily __________, which causes _____ __________

- weak

- (easily) damaged

- GI bleeding

Management of acute variceal bleeding - goals: ________ bleeding, _________ rebreeding and avoid acute complications such as ______

- control (bleeding)

- prevent (rebreeding)

- SBP

SBP = spontaneous bacterial peritonitis

Management of acute variceal bleeding - stabilize blood volume: to ____________ stability and Hgb ___ g/dL

- hemodynamic (stability)

- 8 (g/dL)

Management of acute variceal bleeding

stabilize blood vlume

- hemodynamic stability

- Hgb ~ 8 g/dL

Airway management

fluid resuscitation

Management of acute variceal bleeding - pharmacological therapy

octreotide (SANDOSTATIN)