Liver Disorders: Cirrhosis

Liver

Largest visceral organ; 2.5% of TBW

Metabolic

Hematologic

Bile production

Functions of the liver

true

- stomach → duodenum → liver

- extracts nutrients and minerals

T/F: All blood leaving absorptive areas must first travel through the liver

DEAK

Fat-soluble vitamins

Vitamin A

Which vitamin is for vision?

Vitamin D

Vitamin needed for the absorption of calcium

Vitamin E

Vitamin that is an antioxidant

Vitamin K

Vitamin important for clotting

glucose (as glycogen), iron, and copper

What does the liver store?

Ammonia (NH3)

Clostridium difficile

Which toxins does the liver remove?

Jaundice: yellowing of skin

Icterus: yellowing of the whites of the eyes

When hemoglobin is broken down into heme and globin (90% reabsorbed), heme changes into unconjugated bilirubin. The liver conjugates unconjugated bilirubin. If the liver is not functioning properly, there will be a decrease in conjugated bilirubin and an increase in unconjugated bilirubin. What does excess unconjugated bilirubin manifest as?

ALT, GGT

Liver-specific enzymes

LDH

Which enzyme is elevated in injury to the liver, pancreas, heart, lungs, or red blood cells and is therefore considered non-specific?

AST

Which enzyme is elevated in injury to the liver and the heart and is therefore non-specific?

MCV

Measures the average size (volume) of RBCs

Decrease in folic acid or B12

*Order labs to figure out which one is deficient, then replace it. For B12, if due to pernicious anemia, must give IM B-12

Causes of macrocytic anemia (MCV > 98)

iron deficiency anemia

*Give iron to treat

Cause of microcytic anemia (MCV < 86)

Albumin

Made by the liver and controls oncotic pressure; manifests as ascites and/or edema in liver impairment

True

- 25% of the total blood supply resides in the liver

T/F: The liver is the largest blood reservoir

Kupfer cells

WBCs that reside in the liver

- phagocytic; removes pathogens

2, 7, 9, 10

Vitamin K-dependent factors

cholesterol

Bile salts are made of cholesterol

1. Bile salts: made of cholesterol

2. Water

3. Ions

4. Conjugated bilirubin

5. Drugs: Doxycycline

6. Copper: excreted in bile

Bile contains

Propranolol

Which medication undergoes the second-pass effect?

Liver

- transfers cholesterol using LDL, HDL, and VLDL

Which organ is primarily responsible for synthesizing and releasing cholesterol?

Angiotensinogen

Which liver-produced protein helps regulate blood pressure through the renin-angiotensin system?

Insulin, ADH, aldosterone, estrogen, testosterone, and epinephrine.

Which hormones are broken down by the liver?

The liver has 4 lobes:

- Right

- Left

- Caudate

- Quadrate

How many lobes does the liver have? What are they called?

Amylase and lipase; located in the pancreas

Carbs are broken doen by ____ and ____, which are located in the ____

Bile salts

____, which are located in bile, are responsible for breaking down lipids

Pepsin

Pepsinogen, in the presence of acid the stomach, is broken down to _____, which is responsible for breaking down proteins.

Porta hepatis

The doorway to the liver with three vessels attached to it: hepatic artery, portal vein, and bile ducts

Esophagus

Stomach

Spleen

Small and Large Intestines

Anus

Where does the portal vein drain?

hepatic artery

Oxygenated blood is transferred to the liver through the ____

To carry nutrient-rich, deoxygenated blood from the gastrointestinal tract and spleen to the liver for processing.

What is the primary function of the portal vein?

1. Folic acid: megaloblastic anemia

2. Thiamine [B1]

3. Pyridoxine [B6]

- sometimes observed as peripheral neuropathy

4. Cyanocobalamin [B12]: megaloblastic anemia

- test for intrinsic factor

5. Vitamin E

6. Vitamin K: increased INR

7. Possible: magnesium, ascorbic acid, zinc

Common nutritional deficiencies seen in liver disorders

Vitamin B6 (pyridoxine)

A deficiency in which vitamin manifests as peripheral neuropathy?

Destroying cells: RBCs, WBCs, platelets

What is the spleen responsible for?

Increased destruction of cells: RBCs, WBCs, platelets

- Destruction of RBCs: increased unconjugated bilirubin, causing jaundice and icterus

- Destruction of WBCs: reduced immune response

- Destruction of platelets: increased INR, PT

Portal hypertension can cause enlargement of the spleen. Why is splenomegaly problematic?

Anemia

Thrombocytopenia

Leukopenia

Hematologic manifestations of spenomegaly

Watchful waiting: monitor blood counts and treat the underlying cause (portal hypertension)

Treatment approach for splenomegaly

Pneumococcal, Haemophilus influenzae type b (Hib), and Meningococcal vaccines

What vaccines are recommended after a splenectomy to prevent infection?

Skip the next dose (if on anticoagulation) or give vitamin K and recheck INR.

What is the first step in managing a mildly elevated INR in a patient with liver disease or vitamin K deficiency?

Mephyton 2.5-5 mg PO

Aqua-Mephyton 1-2 mg IV

What are the two forms vitamin K used to correct elevated INR or PT?

When oral absorption is impaired or rapid correction is required.

When is IV vitamin K preferred over oral?

When immediate correction of coagulopathy is needed, such as in active or severe bleeding, because FFP provides clotting factors directly while vitamin K takes hours to restore synthesis

When are Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC) preferred over vitamin K for treating bleeding tendencies?

increase in unconjugated bilirubin and a decrease in urine urobilinogen

Hyperbilirubinemia is caused by an increase in ___ bilirubin and a decrease in urine _____

1. Phenobarbital 105 mg/kg/day (first option for adults)

2. Phototherapy for children

3. Rhogham

4. IVIG 500-1000 mg/kg/day (second option for adults)

Treatment options for hyperbilirubinemia

Phenobarbital 105 mg/kg/day (first option for adults)

Treatment for hyperbilirubemia that induces UDP-glucuronyl transferase, the liver enzyme that conjugates bilirubin and makes bilirubin more water-soluble, allowing it to be excreted.

Phototherapy

Uses blue light to convert unconjugated bilirubin into water-soluble isomers that can be excreted in urine and bile without conjugation.

- Standard treatment for newborn jaundice

IVIG 500-1000 mg/kg/day (second option for adults)

Treatment for hyperbiirubinemia that blocks Fc receptors on macrophages, which reduces phagocytosis of antibody-coated RBCs, lowering bilirubin production.

Urobilinogen

gives waste products its characteristic color

- in hepatic dysfunction: feces turn gray and urine becomes dark

Ascites

accumulation of excess fluid in the peritoneal cavity due to decreased albumin levels, leading to a decrease in oncotic pressure

- common complication of portal hypertension and liver cirrhosis

25.4 mmHg

When albumin levels drop and oncotic pressure decreases below ____, fluid leaks into the abdominal cavity, causing ascites and edema.

2 g/day

Sodium resitriction for ascites.

Albumin

Which plasma protein primarily binds acidic drugs in the blood?

Phenytoin, Warfarin, and Digoxin

List some acidic drugs whose free concentrations increase when albumin levels fall in liver disease.

Paracentesis

Direct removal of fluid from the abdomen by a needle.

If >5L has been removed with paracentesis, replace with 25% albumin at 6-8 g/L of fluid removed to prevent circulatory collapse

When should albumin be administered for ascites?

If ≤ 5 L has been removed with paracentesis, admister a plasma expander like Dextran 70 or Hydroxyethyl starch to maintain volume.

When should Dextran or hydroxyethyl starch be administered for ascites?

Spironolactone 100-200 mg/day (titrate)

Diuretic of choice for ascites

Furosemide 20-40 mg/day (up to 160 mg/day)

Preferred diuretic in patients with renal failure who have ascites

Midodrine 7.5-12.5 mg PO TID (off-label)

α₁-agonist that increases vascular tone and renal perfusion, helping improve response to diuretics used for refractory ascites in addition to Furosemide.

Esophageal varices

Dilated veins in the lower esophagus that form when blood flow through the liver is blocked by portal hypertension

hepatic encephalopathy

In patients with esophageal varices, the blood seeps from the esophagus into the stomach, where the protein in blood is changed to ammonia (NH3). Ammonia has no electrical charge, so it can cross the blood-brain barrier.

Normally, the liver detoxifies ammonia by converting it to urea for excretion. In liver failure, ammonia builds up, causing _____.

Beta-blockers:

- Propranolol 20-160 mg PO BID

- Nadolol 20-160 mg PO QD

- Carvedilol 6.25-12.5 mg QD

Prophylactic treatment for esophageal varices; reduces portal pressure by decreasing cardiac output and splanchnic blood flow.

Octreotide 50 mcg/hour IV infusion for 3-5 days

Somatostatin analog that constricts splanchnic (gut) circulation, slowing portal venous blood flow, lowering pressure in varices.

- first-line for acute variceal hemorrhage

Terlipressin 2 mg IV bolus, then 1-2 mg IV Q4-6 hours for up to 48 hours

- use Vasopressin if Terlipressin is unavailable

Potent vasoconstrictor that reduces portal venous inflow used as second line treatment in esophageal varices

Ceftriaxone 1 g IV for 5-7 days

Prophylactic antibiotic for esophageal varices

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Procedure that reduces pressure in the portal vein by shunting blood away from the scarred liver

- Used for refractory bleeding in patients with esophgeal varices

Hepatic encephalopathy

Ammonia is produced by intestinal bacteria that break down proteins. Normally, NH3 is converted by the liver into urea and excreted by the kidneys. In liver failure, this detoxification doesn't happen, so NH₃ (lipid-soluble) accumulates and is able to cross the BBB, causing _____.

1.2-1.5 g/kg

Protein restriction for hepatic encephalopathy

Lactulose 30-45 mL PO 2-4 times daily

DOC for hepatic encephalopathy; acidifies the colon, converting NH3 (ammonia; lipid-soluble) to NH4+ (ammonium; water-soluble), which is excreted in the urine

Rifaximin 550 mg PO BID

Poorly absorbed oral antibiotic that kills ammonia-producing gut bacteria; prevents recurrence of HE

- minial resistance

Neomycin 4-12 g/day

Second line antibiotic used in HE to prevent gut bacteria from producing ammonia

- not used much anymore due to ototoxicity and nephrotoxicity

L-ornithine L-aspartate (LOLA/2 amino acids) 20 mg/day in 500 ml over 4-6 hours

Adjunct therapy to lactulose and rifaximin that enhances urea cycle and increases ammonia detoxification