Liver Flashcards
Where is live Located?
Located in RUQ of abdomen
2 lobes made up of thousands of lobules
Lobules function:
centered on a branch of the hepatic vein (“central vein”)
interconnected by small ducts
contain hepatocytes, separated by sinusoids
“portal triads”at the corners of adjacent lobule–>branches of the bile duct , portal vein, hepatic artery
What is the heaptic duct?
Transports bile produced by liver cells to the gallbladder and duodenum
Unique function of liver cells
Liver cells can regenerate
About 70% of the liver tissue can be destroyed before the body is unable to eliminate drugs and toxins via the liver
Blood flow to liver
~25% of the cardiac output (~1500 mL of blood flow/minute)
Has a dual blood supply
Describe the blood supply flow to the liver
venous flow in from the portal vein*
venous blood from the small intestine (absorbed nutrients, drugs, toxins) directly to the liver
pancreatic venous drainage (pancreatic hormones)
spleen (bacteria, byproducts of blood-cell recycling)
arterial flow in from the hepatic artery
liver oxygenation
venous flow out through the hepatic vein
Blood from both portal vein and hepatic artery mixes together in sinusoids and exits the liver through the hepatic vein
Connected to the GI tract via portal veins and bile ducts
Major functions of the liver
Excretion
Bile* - produced by hepatocytes; metabolizes cholesterol and fat and detoxifies drugs and toxins
Metabolism
Bilirubin, drugs, nutrients, hormones
CHO, lipids, amino acids, hormones/steroids
Storage
Vitamins/minerals (B12, iron), CHO
Synthesis
Plasma proteins (albumin, coagulation proteins, other transport proteins)
Responsibility of gallbladder
Stores and concentrates bile (typically concentrated 5 fold in the gallbladder by absorption of water and electrolytes)
Bile Functions
Bile functions:
Emulsification: dietary fat, chol, vitamins
Elimination of waste: excess chol, xenobiotics, bilirubin
contraction of Gallbladder and bile duct is by…..
Stimulus (food in duodenum) Cholecytikinin
What is enetrohepatic recirculation?
enterohepatic recirculation (95% of bile acids reabsorbed) – some lost in feces, body makes up for it
What is Bilirubin? What is its metabolism?
End product of heme degradation
From breakdown of RBC in spleen/liver
Free bilirubin –> Insoluble-bound to albumin for transport to liver (measured as “indirect bilirubin”)
Bilirubin Metabolism:
Glucuronidated in liver (“direct bilirubin”)
Excreted in bile
Describe billirubin process
Liver Dx can be….
Can be acute or chronic, focal or diffuse, mild or severe, and reversible or irreversible…
Describe liver damage and the types? Is it reversible?
Acute damage to the functional cells of the liver without destruction of the liver’s capacity for regeneration is generally reversible (may be irreversible)
Fulminant liver failure/end-stage disease
insufficient residual hepatocytes to maintain minimal essential liver functionsirreversible
Descirbe the pattern of hepatocellular injury?
Etyiology of Hepatic Injury
Viruses (HAV, HBV, HCV, HDV, other Epstein bar virus as example )
Drugs (Rx, OTC, herbals)
Environmental toxins (chlorinated pesticides, insecticides, etc.)
Alcohol
What are the two types of hepatic injury?
CHOLESTASIS
HEPATOCELLULAR
Define cholestasis.Leads to?
A failure of normal amounts of bile to reach the duodenum’
Leads to accumulation of bile in liver cells and biliary passages (intra vs extrahepatic)
Causes of cholestasis
Cholelithiasis (gall stones) - most common
Tumor, viral hepatitis, alcohol-related liver disease, drugs
Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)
What is primary biliary cholangitis. Stat?
Caused by the slow, immune-mediated destruction of small bile ducts within the liver (impaired excretion of bile)
Leading cause of liver transplant in women in Canada
What is primary sclerosing cholangitis?What is it associated with?
Involves progressive inflammation and fibrosis affecting any part of the biliary tree
Leads to the progressive destruction of bile ducts
Commonly associated with inflammatory bowel disease
What is choletstaic syndrome? Sx?
Blockage of bile flow
Pruritis
Jaundice
Dark Urine
Light coloured stools (greenish)
Steatorrhea (fatty stools)
Xanthoma (growths under skin due to bile salts) and xanthelasma (little growths around the eyelids)
Hepatomegaly
Treatment of choleithiasis?
Ursodeoxycholic acid (ursodiol
MOA of Urosodiol
Naturally occurring bile acid (bile salt) – small amount endogenously
MOA unclear: decrease chol saturation
How are gall stones formeda nd removed?
Gall stones – super-saturation of cholesterol which causes precipitation
- Eliminated on their own, or they can be removed through laparoscopic surgery
Cholethialisis Urosodiol and Counselling
Stones often recur after drug d/c
Urosodiol Dose, A/E
Dose is often 250-500 mg BID – take until stones are gone or 1-3 months after
Genrally well tolerated; limited D.I. – may complain of some pruritis
Urosodiol can also be used in…. to…
Also used in chronic forms of cholestasis such as PBC or PSC
Improves serum biochemical tests
Limited efficacy in preventing disease progression in PSC
Alternative to ursodiol in PSC
Obeticholic acid (OCA) – may use as alternative in PBC
Semi-synthetic bile acid
Pruritis
Often associated wit long standing cholestasis
Rule out local cutaneous causes of pruritus such as eczema
Tx of Pruritis Algorithm
Cholestyramine (best drug – bile acid sequestrant)
will benefit about 90% of patients; must be continued as long as pruritus is present
Binds to bile salts and prevents reabsorption
Antihistamines
(e.g., hydroxyzine) are of no proven benefit, but their sedative properties may help
Naltrexone (opiod antagonist), rifampin (antibio) or sertraline (anti-depressant)
may be tried if refractory
Hepatiocellular damage definition
Direct damage to hepatocytes
Injury may be acute or chronic
Cuases of heaptocellular damage
Toxic agents: Alcohol, drugs, toxins
Infections: Hepatitis
Longstanding cholestasis (can lead to hepatocellular injury as well)
Ischemic injury: Thrombosis
Other Diseases (autoimmune, iron overload)
Course of Heaptocellular DamageDepends on n
Duration of assault (cells can regenerate)
Intensity of assault (massive: fulminant hepatic failure vs mild to moderate: hepatitis)
Tremendous reserve capacity of liver
When hepatocytes are destroyed, what happens?
contents of cells are released into the circulation
functional ability of the liver may be compromised (if enough damage has occurred)
Conditions that can lead to heaptocellular damage?
Autoimmune Hepatitis – autoimmune dx characterized by chronic inflammation of the liver with genetic component
Hemochromatosis – excessive absorption of iron; different types; think of inherited type; may be heterozygous and may not know they have; if homozygeous – will develop sx that may be severe – lead to accumulation of iron in liver, hearts, lungs, joints, ect. –> Could lead to liver transpant TX: Phlebotomy (removal of blood once over twice per month initially)
Evaluating liver function iclcudes:
Liver Enzyme measurement
Testing for enzymes residing inside hepatocytes (release from damaged hepatocytes)
Liver Function tests (LFTs) - abc’s
Evaluate synthetic capacity of liver
Albumin, Bilirubin, Clotting
Liver enzyme measurement includes:
Released into circulation after injury
ALP, AST, ALT, GGT
Liver enzymes measurements are what to liver cells? What do we use them for?
Relatively specific to liver cells
When look at pattern to them -Helps to distinguish type of injury.
Cholestatic
Hepatocellular
Other
Indicators of cholestatic injury
Liver Enzyme elevations in: ALP & GGT
What is ALp? Where is it found?
ALP (Alkaline phosphatase)
Present in bile duct > hepatocytes
High concentrations also found in bone
Marker of cholestatic issues
What is GGt?Also elevated in?
GGT (Gamma glutamyl transpeptidase) – non-specific liver enzyme
Elevated in all liver disorders
Confirms hepatic origin of ALP
Also: EtOH, pancreatitis, MI, COPD, renal
Pattern of ALP and GGT
Ifr ALP is elevated, but GGT is low –> May not be liver
If elevated with GGT, indicates liver involvement –> More conerned
ASTabd ALt are….
Aminotransferases (AST, ALT)
(aspartate aminotransferase, alanine aminotransferase)
Which is more specific, ALT or AST?
ALT more specific than AST
Aminotransferases Correlation and Severity
Poor correlation with severity, prognosis
May be minimally elevated in cholestatic syndromes (if long enough, may increase by direct toxic insult of hepatocytes)
LDH
LDH (LDH5)
very nonspecific
Benefit of liver enzymes.Disadvantage?
often go up before clinical sx goes up so allow for early detection of liver injury – poorly correlated with a severity or prognosis of liver injury
LFT’s measure what?
Test the synthetic capability of the liver
Albumin Normal Lifespan
20 days
Albumin in liver impairement.Sx?
Reduced after sustained assault
Sx: edema, ascites (because you can’t maintain oncotic pressure)
Effects on calcium, highly bound drugs (phenytoin).
When do see albumin decreasing?
- Delay before you see a change in serum albumin following liver injury
- Sustained assault to the liver – will not see this in acute hepatitis
Bilirubin does what in liver damage? Sx?
‘Bilirubin’ (Goes up)
Result of bilirubin retention
Deposits in skin and tissues
Dark urine, pale stools, yellow skin (jaundice)
Causes of Bilirubin increase?
Obstruction: Cholestasis
Impaired metabolism: Hepatocellular
Excessive production: e.g hemolytic anemia (increased breakdown of RBC, increase in unconjugated biliiribuin)
Unconjugated Bilirubin
Unconjugated bilirubin HIGH – bound to albumin and not soluble in water; measured as indirect
Conjugated by the liver
Conjugated bilirubinemia – conjugated by the liver, soluble in the liver, measured as direct
Clootting PT?
Liver synthesizes coagulation factors (I, II, V, VII, IX, and X) in excess. Increased bleeding times.
80% of capcity needs to be lost before see a change
- Acute: would not see this as well
Only seen after moderate to significant damage
Note: Vit K deficiency
Big 7 Lab Tests
Alcohol Related Enzymes
Modest incr <10x
AST>ALT – 2:1
Chronic if albumin low
Define Cirrhosis
A chronic diffuse disease characterized by fibrosis and nodular formation
Cirrohosis is a result of…How long to dvelop?Effects the livers ability to what?
Result of continuous liver injury
Takes a long time to develop
Overwhelms the body’s ability to regenerate
Cirrohosis effect on liver presentation?Leads to?
liver becomes hard, shrunken, and nodular
Loss of normal structure and function
Irreversible fibrosis (scarring) – can’t go back as so much scarring (liver transplant)
Causes of cirrohos?
alcohol, viral, autoimmune, inherited, drugs/toxins, Non-alcoholic fatty liver disease, etc
Different types of liver dx??
Alcohol-related liver disease (ALD)
Non-alcoholic fatty liver disease (NAFLD); now known as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Non-alcoholic steatohepatitis (NASH); now known as Metabolic Dysfunction-Associated Steatohepatitis (MASH)
MASLD and increased alcohol intake (MeALD)
Guidelines for alchol intake?
All levels of alcohol consumption are associated with some risk, so drinking less is better for everyone.
Among healthy individuals, there is a continuum of risk :
Negligible to low for individuals who consume ≤ two standard drinks /wk
Moderate for those who consume between 3 and 6 standard drinks /wk
Increasingly high for those who consume ≥ six standard drinks /wk
Recommendations for alcoohol?
On any occasion, any level of consumption has risks, and with >2 standard drinks, most individuals will have an increased risk of injuries or other problems
Disproportionately more injuries, violence and deaths result from men’s drinking.
Above low levels of alcohol consumption, the health risks increase more steeply for women than for men.
It is safest not to drink alcohol while pregnant and during the pre-conception period.
For women who are breastfeeding, it is safest not to use alcohol.
Are the recommendations specific to alcohol?
hese recommendations are to minimize all alcohol-related risks, not just those related to the liver
Drink Equivalents
12 oz. (341 ml) of beer
12 oz. (341 ml) of a cider or cooler
5 oz. (142 ml) of wine
1 ½ oz. (43 ml) of spirits
Alcohol needed for cirrhosis quantity?
Metanalysis
No increased risk for occasional drinkers.
Consumption of 1 drink per day in = increased in women, but not men
Drinking ≥5 drinks per day = substantially increased risk in women + men
How is cirrhosis diagnosed?
Biochemical Marker
Scoring Systems using biochemical marker
Fibrosis-4 (FIB-4) score
helps to estimate the amount of scarring in the liver/risk of fibrosis using age, platelet count, AST and ALT
AST to Platelet Ratio Index (APRI)
Used to estimate liver fibrosis specifically in patients with hepatitis C
Abdominal ultrasound
generally the first imaging modality recommended when liver disease is suspected
Elastography (e.g., FibroScan)
Relatively new, non-invasive way to determine liver stiffness
Measures propagation speed of mechanical waves through liver parenchyma
Limitations = low reliability in patients with obesity, ascites and artificially elevated stiffness due to severe liver inflammation or steatosis
Liver Biopsy
Rarely needed now for diagnosis
Still has a role in definitive diagnosis of underlying cause
Invasive
Cirrohsosis results in:
↓ functioning liver tissue
impaired function and diminished reserve
Portal HTN (portal-to-systemic shunting)
Death Cirrohosis
Patients will die ~5-15 years after dx of cirrhosis
TX Cirrohosis
Of the specific disease
Of the complications (bleeding esophageal varices, ascites, encephalopathy)
Liver transplantation
Cirrhosis presnetation types:
Compensated, Decompensated
Compensated Cirrohosi
body functions fairly well despite scarring of the liver
May be asymptomatic
Nonspecific symptoms:
Anorexia, weight loss, weakness, NV, GI upset, muscle wasting
LETs may be abnormal (or normal)
Decomensated cirrohosis
severe scarring & disruption of function
Symptoms
confusion, edema, fatigue, bleeding
Abnormal LFTs
INR, albumin, bilirubin
Abnormal exam
Signs of chronic liver disease
Portal HTN, ascites, varices, encephalopathy
Signs and sx of cirrohosis
Asymptomatic
Splenomegaly (enlarged liver)
Jaundice, palmar erythema, and spider nevi (collection of vessels close to the skin)
Ascites and edema
Malaise, anorexia, and weight loss
Encephalopathy (disturbance in brain; accumulation of gut compounds in systemic circulation)
Testicular atrophy, loss of body hair, ammenorrhea, gynecomastia
Laboratory findings cirrhosis
Hypoalbuminemia
Elevated prothrombin time (PT)
Thrombocytopenia
Elevated alkaline phosphatase (ALP)
Elevated aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT)
Elevated bilirubin
Compplications cirrohois
Portal hypertension
Ascites
Spontaneous Bacterial Peritonitis
Hepatorenal syndrome
Varices
Encephalopathy
What is the portal system normally?
Normally self-contained, low-pressure venous system
Describe portal HTN?
If blood flow through the liver is obstructed, pressure is increased (“portal HTN”)
Opens “detours” between the portal and systemic circulation
blood is diverted around the liver rather than filtered through the liver
Portal blood bypasses the liver and directly enters systemic circulation (“portal-to-systemic shunting”)
What causes portal HTN?
Results from increase in resistance to portal flow and increase in portal venous inflow
Splanchnic dilatation
Increase in NO leading to vasodilated state
RAAS
Result of portal HTN on vasculature?
End up with “back flow” of blood and widening of the venous channels that connect the portal and systemic circulation
Portal HTN can lead to….. which can lead to….
Spleen enlarges 3-6x
May be uncomfortable/painful to patient
↑ sequestering and destruction of RBCs
Anemia (common finding with someone in cirrhosis but also nutritional deficiencies)
thrombocytopenia
Consequences of Portal-to-systemic shunting
Portal blood bypassing the liver:
metabolites/toxins in the blood have not been processed by the liver first
↑ sensitivity to noxious substances absorbed from the GI tract (encephalopathy)
malabsorption of fat in the stool (↓ bile flow)
Contributes to all other complications as well: ascites, SBP, varices, hepatorenal sx
What is ascites?
Collection of fluid in the peritoneal cavity
Many liters may collect (up to 20L +)
Can cause massive distension
Pathology of ascites?
Hydrostatic pressure
Hypoalbuminemia (reduced oncotic pressure)
Causes relative hypovolemiaaldosterone secretion in response
Renal retention of Na+ and water
Patients with ascites should be considred for?
Patients with ascites should be evaluated for liver transplant b/c of poor prognosis
Aspiration of Ascitic Fluid?
Aspiration of ascitic fluid and laboratory analysis is an essential step in the management of patients with newly diagnosed ascites
Review: wbc, total protein concentration and albumin
What test can be used to analyze the need for aspiration of ascitic fluid?
SAAG (serum-ascites albumin gradient)
= serum albumin – ascitic fluid albumin
If ≥11 g/L indicates portal hypertension
Likely responsive to diuresis
If <11 g/L likely other causes (e.g. infection, malignancy
Not typically responsive to diureses
Total protein concentration
If ascitic>25g/L associated with a SAAG of >11 g/L suggest cardiac dysfunction as the etiology of ascites
Goal of management of ascites
Remove abdominal fluid
Prevent sx and maintain reasonable QOL
Management of ascites
Salt restriction
Diureses
Paracentesis
TIPS
Liver Transplant (only true cure)
Algorithm for tx of adscites
For diuresis of ascites, what med is used?
spironolactone +/- furosemide
Spironolactone is diuretic of choice here
What is paracentesis?
Aspiration of peritoneal fluid with a needle
Risks and solution with paracentesis
Large volume aspiration may result in “fluid steal” from the vascular space – hypovolemia –> acute renal failure
Paracentesis + Albumin may be helpful (often give albumin to maintain oncotic pressure)
May help ↓ discomfort
Risk of abdominal perforation and infection (risk is low; clinicians are good at this)
NOT a cure; will come back refractory ascites paracentesis on a scheduled basis
What is TIPS?
Transjugular Intrahepatic Portosystemic Shunt
Create an artificial tunnel through the use of a stent from inflow portal vein and outflow hepatic vein
Only cure of ascites
Transplant
What is no longer recommended for ascites?
bed rest no longer recommended
fluid restriction is no longer
recommended unless serum sodium is <120-125 mEq/L (hyponatremia)
Spironolactone MOA
Inhibits the effects of aldosterone
Generally a weak diuretic and anti-HTN med unless aldosterone levels are ↑
Spironlactone Onset
Onset generally delayed 3-5 days
A/e Spironolactone
Hyperkalemia (cause of many DIs)
Dehydration (not common from monotherapy)
Estrogen-like side effects (gynecomastia, decreased libido in males; menstrual irregularities and breast tenderness in females)
D.I. Spironolactone
DI: Drugs affecting K & may incr digoxin level
Furosemide MOA
MOA:
Loop diuretic
Furosemide A/E
Caution with over-diuresis
Potent diuretic: hypovolemia much more common
Diuretic Dosing and Titration
Usual diuretic regimen consists of a single am dose of spironolactone 100mg & furosemide 40mg od (much lower in HTN, generally this regimen for cirrohosis)
Titrate therapy q3-5d using ratio of 100mg:40mg to max of 400mg spironolactone & 160mg furosemide.
Other diuretics qand usage for ascites
Metolazone can be added if ascites is refractory to spironolactone and furosemide
Amiloride can be substituted for spironolactone if intolerable side effects
Monitoring diuretics for ascitees
Monitoring is important!! (watch renal function; risk of hypovolemia, post hepatic renal syndrome)
SCr, Na, K
Weights and blood pressure
What is refractory ascites? Prognosis and avoid?
Unresponsive to sodium-restricted diet and high-dose diuretic treatment
(400 mg/day of spironolactone and 160 mg/day of furosemide)
Recurs rapidly after a therapeutic paracentesis & high-dose diuretics
Poor prognosis
AVOID NSAIDS
Tx refractory ascites
serial therapeutic paracentesis, (+/- albumin)
transjugular intrahepatic portasystemic shunt (TIPS),
or liver transplantation
Monitoring therapy of ascites
Patients should monitor daily weights
Gradual weight loss is the goal
<0.5kg/d if no peripheral edema, more if edema
Edema with ascites; go a bit faster
*Assumes 1kg body wt = 1L of fluid
If no response, check urinary sodium
if low - more diuretic
if high – non-adherence to low Na diet: counsel
Monitor creatinine, serum Na & K frequently
Consider SBP – treatment and prophylaxis (spontaneous bacterial peritonitis)
What is SBP? Cause?
Infection in ascitic fluid without obvious cause
Thought to be from bacteria translocation (the passage of bacteria from the gut to the bloodstream and other extraintestinal sites, together with decreased host defenses
Sx of SBP
Sx of fever, chills, abd pain, etc..
Although typical symptoms may be absent
SBP Risks
Mortality rates are high and presentation is variable so a diagnostic paracentesis should be performed as soon as a patient with ascites and cirrhosis is hospitalized emergently, of has suggestive symptoms
Most common bacteria of SBP?
E coli, Klebsiella pneumoniae, Streptococcus pneumoniae
Tx of SBP
Empirically treat:
Culture positive
PMN >250/uL OR a high degree of suspicion for SBP (do not wait for culture if you don’t have one)
Use broad spectrum empiric therapy
Community acquired
Cefotaxime or ceftriaxone x 5 days
Hospital acquired
Piperacillin/tazobactam
meropenem±vancomycin
Albumin infusions may be added as well
Monitoring of EMpirirc Anti-bio for SBP.Clinical Response?
Second ascitic fluid collection recommended 48h after initiation
Clinical response=decrease in PMN count by 25%
Prophylaxis of SBP. WHich ones?
Consider prophylaxis for pts having survived an episode of SBP (secondary prophylaxis), or those at high risk (primary prophylaxis)
(High risk= low ascitic fluid total protein ascites or variceal hemorrhage)
ex: norfloxacin, septra or ciprofloxacin
After SBP, pt should be considered for:
Patients should be referred for liver transplant if eligible after experiencing SBP
What is hepatorenal syndrome?Due to?
Renal failure in patients with severe liver dz
Characterized by severe vasoconstriction of the renal circulation (activation of RAAS)
In hepatorenal, would see kidney changes?
No pathologic changes are identifiable in the kidney (due to hemodynamic changes)
renal abnormalities associated with liver disease are functional (usually improve with transplant)
When does hepatorenal syndrome occur?
Typically occurs in patients with massive, tense ascites
may be precipitated by aggressive diuresis or SBP
Tx Hepatorenal Syndrome
Stop diuretics
Avoid all potential nephrotoxins such as NSAIDs & aminoglycosides
What are varices?
High pressure in portal vein
Creates “bypasses” or shunts (collaterals – collateral veins)
Relatively small veins become engorged with an excess of blood (Varices)
Principal sites of varices
Veins in rectal area (hemorrhoids)
Abdominal wall (umbilicus)
Esophageal varices (Most common here)
Esophogeal Veins rates
65% of patients with advanced cirrhosis
Veins become enlarged and tortuous (twisted)
Can easily rupture causing massive bleeding
Complicated by clotting disorders
Causes massive hematemesis
7-15% mortality
Risks of esophogeal varices?
Very difficult to stop the bleeding
High risk of recurrent hemorrhage
Possible prophylaxis (primary/secondary prevention)
A variceal bleed is an….;
acute medical emergency
Tx Goals of variceal blees
Adequate blood volume resuscitation
Protection of airway from aspiration of blood
Prophylaxis against SBP and other infections
Control of bleeding
Prevention of re-bleeding
Preservation of liver function/prevention of hepatic encephalopathy
Prevention of acute kidney injury
Treatmennt of variceal bleeds
Packed red blood cells
To resuscitate blood volume
Goal hemoglobin 70-90g/L
Antibiotic prophylaxis for SBP
greater chance of infection with bleeding
Ceftriaxone, cipro, septra, norfloxacin (during acute event)
Octreotide or somatostatin IV
Vasoconstrictors which decreased splanchic blood flow
Used to stop or slow bleeding
Can be discontinued once free of bleeding for at least 24 hours (ICU tx setting)
Endoscopic therapies
band ligation
More effective > control of hemorrhage, less risk for rebleeding, decreased likelihood of adverse events, decreased mortality) – tie off the bleed with band
Sclerotherapy – inject sclerosing agent into the vein to stop it from bleeding by endoscope –>Gastric varices
TIPS
For those who fail to achieve or maintain hemostasis despite combined endoscopic and pharmacologic therapy
Prevention of variceal bleed?
Prophylaxis should be given to
Patients with small varices + increased risk of bleeding
Child Pugh C (severe cirrhosis), Portal pressure >12mmHg
Previous bleed, continued alcohol use
Patients with medium/large varices
Non-selective beta-blocker examples
Propranalol and Nadalol
MOA of Nadalol and Propranalol
decreased portal venous pressure via
decreased cardiac output
unopposed alpha vasoconstriction leading to arteriolar splanchnic vasoconstriction
Effectiveness of Non-selective beta-blockers
Reduces bleeding incidence by up to 50%
Portal pressure <12mmHg?
Sqafety Non-selective ebta-blockers
Asthma (beta-agonsists), mask sx diabetes
Beta blocker s/e
Refractory ascites (watch hypotension)
Nadalol Dosing Regimen
Initial 20mg OD
- Max: 240mg/day (or 120mg with ascites)
- Titrate q3-4 days
- Minimal CNS effects
- 70% excreted unchanged (primarily renally unchanged)
Propranalol Dosing regimen
Initial 20mg BID
- Max: 320mg/day (or 160mg with ascites)
- Titrate q3-4 days
- 0.5% excreted unchanged (1A2 substrate)
Titration of betablocker
***Titrate Bbl to 25% decrease in resting HR or pulse 55bpm
Prevention of Variceal bleeding primary and secondary
Primary prophylaxis:
Non-selective beta blockers
EVL
May be preferred if high risk of bleed, refractory ascites, SBP
Secondary prophylaxis:
Non-selective beta blocker + EVL
TIPS for those who have re-bleeding despite therapy
What is hepatic encephalopathy?
CNS dysfunction observed in late-stage cirrhosis
Cause of encephalopathy?
Accumulation in the bloodstream of neurotoxic substances that are normally removed by the liver
MOA not entirely clear but a number of substances have been implicated
Ammonia pathway (treatment targeted here as of rn)
Tryptophan pathway
GABA’ergic compounds pathway
Encephalopathy Presentation Stages
Grade 1:
Changes in behavior, mild confusion, slurred speech, disordered sleep
Mild Tremor, anxiety, impaired hand writing
Grade 2:
Lethargy, moderate confusion
Ataxia, asterixis, personality changes
Grade 3:
Marked confusion (stupor), incoherent speech, sleeping but arousable
Seizures, muscle twitching, delirium, bizarre behavior
Grade 4:
Coma, unresponsive to pain
Management of encephalopathy started when?
Be alert for signs and symptoms
Confusion, drowsiness, asterixis
Treatment should start ASAP if symptoms appear
Management of encephalopathy?
identify and correct precipitant
restrict dietary protein (and then re-add once tolerated)
avoid CNS depressants ex: BZD
most therapies aimed at lowering blood ammonia []’s
lactulose, antibiotics
Other
What is lactulose?
Synthetic disaccharide (galactose + fructose)
Not absorbed in the gut(can be used in diabetes)
MOA of lactulose
Degraded by colonic bacteria to formic, acetic, and lactic acids
Reduces pH reducing ammonia absorption, decreases production of urease-producing bacteria
Reduces GI transit time
First line (cheap, readily available, safe except for diarhhea)
Dosage of Lactulose. Onset?
Dosage: (15ml=10g lactulose)
15-45ml tid-qid
Onset 12-48 hours
MD of Lactulose
Maintenance dose: 2-3 soft formed stools/day (or less if mental status improves at a lower dose)
Can ↓ dose once mental state improves, often d/c within days to weeks (rarely may see long term usage)
Lactulose Tolerance
Very sweet (fruit juices or pop may help)
GI: Nausea, gas, bloating, diarrhea
Alternatives to lactulose?
Metronidazole
Sterilizes GI tract & inhibits activity of urease-producing bacteria, decreasing production of ammonia
Limited used due to adverse effects (e.g. peripheral neuropathy associated with long term use)
Bacterial resistance
Rifaximin
non-absorbable derivative of rifampin (MOA as above)
at least as effective as lactulose, but costly
Used in com bo with lactulose
Cirrohosis Gneral Approach
Discontinue alcohol (higher risk; bleeding, medical emergency) – may help improve reversible sx
Avoid ASA/NSAIDS
may contribute to gastritis or GI bleed
blunting diuretic effects in ascites
Avoid sedatives/narcotics if possible
Adequate nutritional intake
Deficiencies are common
Nutritional Deficiences in Liver DX
Protein calorie and micronutrient deficiencies are common
Multifactorial
Decreased dietary intake
Malabsorption/Digestion
Overall loss sof protein ADEK vitamins
N=Deficiences with hevay alcohol use
Thiamine (vitamin B1)
Deficiency–> Wernicke’s Encephalopathy
Prevention:
200mg/day (oral)
Pyridoxine (vitamin B6)
Supplementation of 2mg od suggested
Folate
Supplementation of 400 ug od suggested
Consider multivitamin
