Hepatic (3) Flashcards
How is non-alcoholic liver disease diagnosed?
Hepatocytes contain >5% fat→ Dx with imaging and histology
What are some causes of non-alcoholic fatty liver disease?
- Obesity
- Insulin resistance
- DM2
- Metabolic syndrome
What can NAFLD progress to?
- NASH (non-alcoholic steatohepatitis)
- Cirrhosis
- Hepatocellular carcinoma
______ and ______ have become additional leading causes of liver transplant in the US.
Non-alchoholic fatty liver disease
Non alcoholic steatohepatitis (NASH)
What is the treatment for NAFLD? When is a liver transplant indicated?
Diet and exercise
Liver transplant indicated for advanced fibrosis, cirrhosis related complications
___ out of 4 people have NAFLD regardless of weight
1
What are the 2 types of fatty liver disease?
Non alcoholic fatty liver disease
Alcoholic fatty liver disease
How is autoimmune hepatitis diagnosed?
Positive autoantibodies and hypergammaglobulinemia
AST/ALT may be 10-20x normal in acute
Is autoimmune hepatitis acute?
Can be asymptomatic, acute, or chronic
What is the treatment for Autoimmune hepatitis? Is it curable?
*Steroids
*Azathioprine (immunosuppressant)
60-80% achieve remission–relapse is common
Which group is predominantly effected by autoimmune hepatitis
Women
What is the most common cause of drug induced liver injury? Is it reversible?
Acetaminophen OD
*normally reversible after drug is removed
What are the 3 disorders characterized as inborn errors of metabolism?
- Wilsons Disease
- Alpha-1 Antitrypsin deficiency
- Hemochromatosis
What are inborn errors of metabolism?
Group of rare, genetically inherited disorders that lead to a defect in the enzymes that breakdown and store proteins, carbs, and fatty acids
How common is wilsons, alpha-1 antitrypsin deficiency, and hemachromatosis?
1:2500 births
onset varies from birth to adolescence
What age is the most severe form of inborn errors of metabolism?
Most severe forms appear in the neonatal period→ high degree of mortality
What is Wilsons disease?
“Hepatolenticular degeneration”
Autosomal recessive disease characterized by impaired copper metabolism
How does copper build up cause issues with the liver (wilsons disease)?
Leads to oxidative stress in the liver, basal ganglia, and cornea
What are the S/S of wilsons disease?
Range from asymptomatic to sudden onset liver failure
Neurologic and psychiatric manifestations
How is Wilsons disease diagnosed?
*Serum Ceruloplasmin
* Aminotransferases
* Urine copper levels
-possible liver biopsy for copper level-
What is the treatment for Wilsons disease?
Copper chelation therapy
Oral zinc→ binds copper in GI tract
What is the function of alpha-1 antitrypsin?
Proteins that protect the liver and lungs from neutrophil elastase → an enzyme that disrupts tissues of the lungs and liver
_____________ is the #1 genetic cause of liver transplant in children
Alpha-1 antitrypsin deficiency
Alpha-1 antitrypsin deficiency is a _______ disorder
Genetic
results in defective alpha-1 antitrypsin protein
How is a-1 antitrypsin deficiency diagnosed? What is the treatment?
Dx: A-1 antitrypsin phenotyping
TX: Pooled alpha-1 antitrypsin works for pulmonary symptoms (doesnt help the liver) \
-Liver transplant is the only curative treatment for liver disease from a-1 antitrypsin deficiency_
What is hemochromatosis?
Excessive intestinal absorption of iron
What could cause hemochromatosis if it is not genetically inherited?
Repetitive blood transfusions or iron infusions
*excess iron accumulates in the organs causes damage to the tissues
What is the clinical presentation of Hemochromatosis?
- Cirrhosis
- Heart failure
- DM
- adrenal insufficiency
- Polyarthropathy
What labs would be elevated with hemochromatosis?
*Elevated AST/ALT
* Transferrin saturation
* Ferritin
How is Hemochromatosis diagnosed?
Genetic mutation testing
*echo/MRI diagnose cardiomyopathies and liver abnormalities
* liver biopsy may quantify iron levels in liver/assess damage
What is the treatment for Hemochromatosis?
- Weekly phlebotomy
- Iron chelating drugs
- Liver transplant
What causes primary sclerosing cholangitis?
Autoimmune, chronic inflammation of the larger bile ducts (intrahepatic and extrahepatic)
What is the MOA of Primary sclerosing cholangitis?
Fibrosis in the biliary tree→ causes strictures (beads on string appearance)→ leads to cirrhosis, ESLD
T/F: Males are at greater risk for primary sclerosing cholangitis.
True; onset 40s
What are the S/S or primary sclerosing cholangitis?
*Fatigue
* itching
* deficiency of fat soluble vitamins (A,D,E,K)
* Cirrhosis
What is Primary Biliary Cholangitis (PBC)?
Autoimmune destruction or bile ducts with periportal inflammation and cholestasis
Can cause liver scarring, fibrosis, cirrhosis
What labs changes are associated with primary sclerosing cholangitis?
- Increase alkaline phosphatase
- Increase gamma-glutamyl-transferase
- positive autoantibodies
How is Primary sclerosing cholangitis (PSC) diagnosed?
*MRCP or ERCP showing biliary strictures w/ dilated bile ducts
*liver biopsy reinforces dx but isnt always performed
T/F: female children are mostly affected by primary biliary cholangitis.
False: MIDDLE age females are mostly affected by PBC
What is the treatment for primary sclerosing cholangitis?
No drug treatments effective→ liver transplant is only long term treatment
re-occurance is common after transplant d/t autoimmune nature
What causes PBC?
Exposure to environmental toxins in genetically susceptible individuals
What are S/S of PBC?
*Jaundice
* Fatigue
* Itching
What labs valves are indicative of primary biliary cholangitis?
- elevated alk phos
- elevated GammaGlutamylTransferase (GGT)
- Positive antimitochondiral antibodies
Why is imaging useful in PBC and what imaging is ordered?
- CT, MRI, MRCP to rule out bile duct obstruction
*Liver biopsy reveals bile duct destruction and infiltration with lymphocytes
What is the treatment for PBC?
No cure, exogenous bile acid slows progression
What qualifies for the diagnosis of acute liver failure?
*life threatening severe liver injury occurring within 6 months after insult
* rapid increase in AST/ALT, AMS, and coagulopathy
Almost ___% of cases of Acute liver failure are drug induced.
50% (majority acetaminophen)
Aside from medications, what are other causes of acute liver failure?
- Viral hepatitis
- Autoimmune hypoxia
- Acute liver failure of pregnancy
- HELLP
What happens with massive hepatocyte necrosis?
Cellular swelling and membrane disruption
What are S/S or acute liver failure?
- Jaundice
- Nausea
- RUQ pain
- Cerebral Edema
- Encephalopathy
- Multi-organ failure
- Death
What is the treatment for Acute liver failure?
Treat the cause
Supportive care
Liver transplant
What is the final stage of liver failure?
Cirrhosis
What is pathophysiology of cirrhosis?
Normal liver parenchyma is replaced with scar tissue
What are S/S of cirrhosis?
Often asymptomatic in early stages
* Progress to jaundice , ascites, varices, caogulopathy, encephalopathy
What are the most common causes of cirrhosis?
- Acute liver disease
- Non-alcoholic fatty liver disease
- Hepatitis C
- Hepatitis B
What labs are elevated with cirrhosis? What is the cure for cirrhosis?
*AST/ALT
* Bilirubin
* Alk phos
*PT/INR
*thrombocytopenia
Transplant is the only cure
What are complications of cirrhosis?
*Portal HTN
* Ascites
* Bacterial Peritonitis
* Varices (50% of pts)
* Hepatic encephalopathy
*Hepatorenal syndrome
* Hepatopulmonary syndrome
* Portopulmonary HTN
What is the most common complication of cirrhosis?
Ascites
What causes ascites associated with cirrhosis?
Portal HTN leads to increased blood volume and peritoneal accumulation of fluid
What is a dietary management of ascites?
Low salt diet
Albumin replacement
What is the TIPS procedure?
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
*reduced portal hypertension and ascites
What is the most common infection related to cirrhosis? How is it treated?
Bacterial peritonitis→ Abx
What meds are used to reduce risk of hemorrhage in patients with varices?
*Beta blockers
* Prophylatic endoscopic variceal banding and ligation
* Refractory bleeding (balloon tamponade)
Why does cirrhosis cause hepatic encephalopathy?
- Build up of nitrogenous waste from poor liver detoxification
- Neuropsychiatric symptoms
What is the treatment for hepatic encephalopathy?
- Lactulose, Rifaximin→ decrease ammonia-producing bacteria in the gut
What is the MOA of hepatorenal syndrome? What is used to treat hepatorenal syndrome?
- Excess production of endogenous vasodilators (NO, PGs)→ decrease SVR and RBF
*TX: Midodrine, ocreotide, albumin
What are the symptoms of hepatopulmonary syndrome?
- triad of chronic liver disease, hypoxemia, intrapulmonary vascular dilation
- Platypnea from R to L intrapulmonary shunt
What is portopulmonary HTN? What causes this?
Pulmonary HTN accompanied by portal HTN
Caused by systemic vasodilation that triggers production of pulmonary arterial vasoconstrictors
What is the treatment for portopulmonary HTN?
- PDE-inhibs
- NO
- Prostacylin analogs
- Endothelin receptor antagonists
Transplant is the only cure
What are the 2 scoring systems to determine the severity and prognosis of liver disease?
- Child-turcotte-pugh (CTP)→ points based on bilirubin, PT, albumin, encephalopathy, ascites
- Model for End Stage Liver Disease (MELD)→ score based on bilirubin, INR, creatinine, sodium
How does alcoholism affect MAC?
Alcoholism increases MAC d/t rapid metabolism
What are anesthesia consideration for patients with liver disease?
- Careful H&P
- Preop labs: CBC, BMP, PT/INR
- Increase risk of aspiration (Hypotension/hypoxemia)
- Slow onset of drugs and prolonged DOA
- Bleeding and coagulation management
What fluids are preferred from resuscitation in patient with liver disease?
Colloids> Crystalloids for resuscitation
Which NMB are ideal for liver patients?
Succs and Nimbex (not metabolised in the liver)
What is the purpose of the TIPS procedure?
- Manage portal HTN
- Stent places between hepatic vein and portal vein
- Shunts portal flow into systemic circulation
- Reduces portosystemic pressure gradient
What are indication for TIPS?
- Refractory variceal hemorrhage
- Refractory ascites
What are contraindications for TIPS?
- Heart failure
- Tricuspid regurg
- Severe pulmonary HTN
When is partial hepatectomy indicated?
Resection to remove neoplasms: leaving adequate tissue for regeneration
How much of the liver can be removed in patient with normal liver function?
Up to 75% is tolerated
Liver resections often cause post op _________ disturbances
Coagulation
Want to maintain low CVP with fluid restriction prior to liver resection. Why?
Reduce blood loss
Functions of the liver:
(there’s sooo many)
- Synthesizes glucose via gluconeogenesis
- Stores excess glucose as glycogen
- Synthesizes cholesterol and proteins into hormones and vitamins
- metabolizes fats, proteins and carbs to generate energy
- Metabolizes drugs via CYP450 and other enzyme pathways
- Detoxifies blood
- Involved in acute phase of immune support
- Processes HGB and stores iron
- Synthesizes coagulation factors
- Aids in volume control as a blood reservoir
How much cardiac output does the liver receive?
25%
- 1.25-1.5 L/min
*highest proportionate COP of all organs
What vessels does the liver receive blood from?
Portal vein and hepatic artery
What two vessels does the portal vein arise from?
Splanchnic vein and superior mesenteric vein
Portal vein blood is partially ____ after perfusing GI organs, ____ & _____.
deoxygenated; pancreas & spleen
How much of hepatic blood flow does the portal vein and hepatic artery provide?
- Portal vein = 75%
- Hepatic artery = 25%
How much O2 delivery does the liver receive from the portal vein and hepatic artery?
- Portal vein = 50% (partially deoxygenated)
- Hepatic artery = 50%
Hepatic arterial blood flow is ____ r/t portal venous blood flow
Inversely
How does hepatic blood flow autoregulate?
The hepatic artery dilates in response to low portal venous flow, keeping consistent HBF
Portal venous pressure reflects ____ arterial tone and ____ pressure
Splanchnic; intrahepatic
What happens with increased portal venous pressure?
Blood backs up into systemic circulation
- esophageal varices
- gastric varices
What is used to determine the severity of portal hypertension?
Hepatic Venous Pressure Gradient
Normal portal venous pressure
HVPG 1-5 mmHg
Clinically significant portal hypertension i.e. cirrhosis, esophageal varices
HVPG >10 mmHg
Pressure for variceal rupture:
HVPG >12 mmHg
Physical liver function assessment:
- Often asymptomatic until late-stage liver disease
- Even later stages may only have vague symptoms like disrupted sleep, decreased appetite
- Rely heavily on “risk factors” for degree of suspicion
Risk factors for impaired liver function:
- Family hx
- Heavy ETOH
- Lifestyle
- DM
- Obesity
- Illicit drug use
- Multiple partners
- Tattoos
- Transfusions
Physical exam findings for impaired liver function:
- Pruritis
- Jaundice
- Ascites
- Asterixis (flapping tremor)
- Hepatomegaly
- Splenomegaly
- Spider nevi
Hepato-biliary function labs:
- BMP, CBC
- PT/INR
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT) *most liver-specific enzymes
- Bilirubin
- Alkaline phosphatase
-ɣ-glutamyl-transferase (GGT)
What are the 3 groups of hepatobiliary disease?
- Hepatocellular injury
- Reduced synthetic function
- Cholestasis
Hepatocellular injury labs:
↑AST/ALT
- Acute liver failure: may be elevated 25x
- Alcoholic liver disease: AST:ALT ratio usually at least 2:1
- NAFLD: ratio usually 1:1
Labs with reduced synthetic function:
↓Albumin, ↑PT/INR
Labs with cholestasis:
↑AlkPhosphatase,↑GGT,↑bilirubin
How is bile secreted?
Hepatocytes secrete ebile through bile ducts into common hepatic duct → gallbladder and common bile duct
- gallbladder stores bile to deliver during meals, common bile duct secretes bile directly into duodenum
Risk factors for cholelithiasis “gallstones”
- Obesity
- high cholesterol
- DM
- pregnancy
- female
- family hx
Symptoms of cholelithiasis:
- RUQ pain, referred to shoulders
- N/V, indigestion
- fever (acute obstruction)
Treatment for cholelithiasis:
- IVF
- Abx
- Pain management
- Lap chole
What the heck does Choledocolithiasis mean?
Stone obstructing CBD→ biliary colic
Initial symptoms of choledocolithiasis:
N/V, cramping, RUQ pain
Cholangitis symptoms:
Fever, rigors, jaundice
Treatment for choledocolithiasis:
Endoscopic removal of stone via ERCP
Endoscopic Retrograde Cholangiopancreatography:
- Endoscopist threads guidewire through Sphincter of Oddi, into Ampulla of Vater to retrieve stone from pancreatic duct or CBD
- GA, usually prone with left tilt (tape ETT to left)
- Glucagon may be required in the event of Oddi Spasm
What is bilirubin?
How is it excreted?
End product of heme breakdown
Unconjugated “indirect” bilirubin is bound to albumin, transported to liver, conjugated into its H2O-soluble “direct” state, excreted into bile
What is Unconjugated (indirect) hyperbilirubinemia?
Imbalance between bilirubin synthesis and conjugation
What is Conjugated (direct) hyperbilirubinemia?
Caused by an obstruction, causing reflex of conjugated bilirubin into the circulation
____ is the most common viral hepatitis requiring liver transplant in the US
Hepatitis C virus
Newer treatment for HCV in the US:
- HCV genotype (75% type 1), HCV stage, +/- cirrhosis
- 12 week course Sofosbuvir/Velpatasvir
- Provides 98-99% clearance of genotype 1A/1B
5 most common types of viral hepatitis
A, B, C, D, E
Common symptoms of acute and chronic hepatitis:
- Fatigue
- Jaundice
- N/V
- Lack of appetite
- Bleeding or bruising
- Dark urine
Characteristic features of viral hepatitis:
What is the most common cause of cirrhosis? And top indication for liver transplants in the US?
Alcoholic liver disease
Treatment for alcoholic liver disease:
Centered around abstinence
- manage symptoms of liver failure
- platelet count <50,000 requires blood transfusion
- Liver transplant an option is criteria is met
Symptoms of Alcoholic Liver Disease:
- Malnutrition
- Muscle wasting
- Parotid gland hypertrophy
- Jaundice
- Thrombocytopenia
- Ascites
- Hepatosplenomegaly
- Pedal edema
- *Sx of ETOH withdrawal may occur 24-72 hours after stopping
Lab values for Alcoholic Liver Disease:
-↑Mean corpuscular volume (MCV)
-↑Liver enzymes
-↑ɣ-glutamyl-transferase (GGT)
-↑Bilirubin
- Blood ethanol (acute intoxication)
