Liver Disease Patho

Question 1

Functions of the Liver

Answer 1

1. Digestive: processing/storing of fats, carbohydrates, proteins, vitamins, minerals
2. Endocrine: metabolism of glucocorticoids, mineralcorticoids, sex hormones
3. Hematological: temporary storage of blood, synthesis of bilirubin from hemoglobin degradation, synthesis of clotting factors
4. Excretory: excretion of bile, cholesterol, synthesis of urea

Question 2

Liver Disease

Answer 2

• Caused by a variety of factors
• Begins as an injury which is on-going and thus continues to cause damage
• Disease progression is not linear and time to progression can be variable

Question 3

Stages of Liver Injury

Answer 3

1. Hepatitis
2. Fibrosis
3. Cirrhosis

Question 4

Hepatitis

Answer 4

• General term for inflammation of liver

- Can be due to alcohol, viral infections, autoimmune disease, fat, medications, illicit substances

Question 5

Fibrosis

Answer 5

• Ongoing inflammation causes progression to fibrosis
• Liver attempts to heal itself during inflammation and gets scarring
• Collagen in liver that encapsulates damaged tissue or is replaced by collagen
• Fibrolytic changes effect blood flow through liver and liver functions

Question 6

Cirrhosis

Answer 6

• Advanced fibrosis with distortion of hepatic vasculature
• Results in impaired hepatocyte function, increased intrahepatic resistance, impairment of all functions, and risk of development of HCC
• Compensated or decompensated

Question 7

Compensated Cirrhosis

Answer 7

• Liver retains functionality despite damage
• Typically see some changes in laboratories (decline in albumin/platelet levels), but otherwise no symptoms
• Often not diagnosed

Question 8

Decompensated Cirrhosis

Answer 8

• Laboratory changes, patients experience clincal events as a result of loss of hepatic function
• Key events: ascites, encephalopathy, jaundice
• Late event: Hepatocellular carcinoma (HCC - liver cancer)

Question 9

Signs/Symptoms of Liver Disease

Answer 9

• Right upper quadrant pain
• Hepatosplenomegaly
• Jaundice
• Caput medusae
• Spider nevi
• Edema
• Ascites
• Gynecomastia
• Loss of body hair
• Fatigue
• Confusion
• Malaise
• Respiratory difficulties

Question 10

Liver Function Evaluation

Answer 10

• No single test for all the functions

- Must look at all functions and piece together to get the big picture

Question 11

Synthetic Function

Answer 11

• “Making things”
• Albumin - important for osmotic pressure and for drug protein binding in PK
• INR: liver makes all coagulation factors AND most of their inhibitors
• Bilirubin: byproduct of hemoglobin degradation which is conjugated and excreted by liver
• Enzymes: Markers of liver damage

Question 12

Indirect (unconjugated) Bilirubin

Answer 12

• Elevations usually due to hemolysis (med. related)

- Gilbert’s disease: lack of glucoronosyltransferase

Question 13

Direct (conjugated) bilirubin)

Answer 13

• Elevations due to blockage of bile duct (gall stones)
• Elevations due to liver disease
• *Liver can still conjugate even with substantial damage**

Question 14

Liver Enzyme

Answer 14

• AST: aspartate transaminase (other organs too)
• ALT: alanine aminotransferase, liver specific (<19 for women, <30 for men)
• ALP/Alk Phos: alkaline phosphatase - found in bone also
• *Once liver cells are severely destroyed, enzymes will not be elevated**

Question 15

Other Lab Clues

Answer 15

• CBC: cirrhosis may be associated with blood count abnormalities
• Hemoglobin/Hematocri: : complications of cirrhosis, blood loss
• Thrombocytopenia: platelets <150,000, platelets get destroyed by portal hypertension causing them to back up in spleen and be damaged/destroyed from high pressure
• Neutropenia: bone marrow suppression from cirrhosis

Question 16

Physical Manifestations of Cirrhosis

Answer 16

• Altered Hormone Metabolism: spider angiomata, gynecomastia, or loss of body hair
• Bile Blockage/Increased Bilirubin: jaundice and pruritus
• Palmar erythema: non-specific finding which could be due to changes from cirrhosis

Question 17

Liver Disease Complications

Answer 17

1. Portal Hypertension
2. Ascites
3. Hepatic Encephalopathy
4. Hepatorenal Syndrome
5. Infections

Question 18

Portal Hypertension

Answer 18

• Blood can’t get through liver, results in collateral/alternate pathway development
• Causes varices and circulatory abnormalities

Question 19

Varices

Answer 19

• Impediment of blood flow through liver results in development of collaterals or alternative pathways for blood flow
• Vessels swell/engorge with blood leading to a bleed risk and increased pressure
• High bleed/rebleed risk (>50% in patients having a bleed in last 10 days)
• Slow bleeds are common with portal hypertension

Question 20

Circulatory Abnormalities

Answer 20

• Portal pressure increases, systemic pressure decreases to compensate
• Leads to splanic vasodilation, hypoperfusion of kidneys, and CO increases to compensate
• Spleen changes => platelet sequestration
• RAAS stimulated and water/salt retained from kidney changes

Question 21

Ascites

Answer 21

• Accumulation of lymph in peritoneal cavity
• Can be due to hypoalbuminemia and portal hypertension
• Hypoalbuminemia: reduced osmotic pressure
• Portal hypertension can force the fluid into the abdominal cavity from vessel dilation from RAAS activation, often seen as fluid in abdomen and edema in lower extremities
• Infection can develop in this fluid: spontaneous bacterial peritonitis (SBP)

Question 22

Hepatic Encephalopathy

Answer 22

• Neurological impairment ranging from confusion to coma
• Ammonia levels can correlate with level of encephalopathy, but don’t use as a guideline to treat
• Also associated with accuulation of nitrogenous substances from gut and accumulation of GABA by endogenous benzo-like substances

Question 23

Hepatorenal Syndrome

Answer 23

• Kidneys compensate for liver dysfunction
• Also try to compensate for changes in systemic pressure
• Kidneys use RAAS and water/salt retention to try to normalize perfusion, but this also causes major stressors and renal impairment
• SBP, infections, and major bleeds can also further renal failure

Question 24

Infections

Answer 24

• Liver plays big role in innate/adaptive immunity
• Compromised with altered blood flow
• Portal hypertension also increased infection risk by causing bacterial translocation or compromised spleen immune function from splenomegaly

Question 25

Testing for Liver Disease

Answer 25

- APRI or FIB-4 to assess likelihood of fibrosis and cirrhosis - Ultrasound, CT, and MRI can also identify cirrhosis - Transient elastography measures liver stiffness (cirrhosis) - Biopsy: gold standard but minimally used since invasive

Question 26

MELD Score

Answer 26

- Risk of 3-month mortality | - Used to evaluate for liver transplant

Question 27

Child Pugh Score

Answer 27

- Used to stage degree of liver dysfunction in cirrhosis patients - Most commonly used to identify drug dosing adjustments needs for liver dysfunction - A: mild dysfunction (5-6 points), B: moderate dysfunction (7-9 points), and C: severe dysfunction (>9 points)

Question 28

Encephalopathy Scores

Answer 28

- None: 1 point - Moderate: 2 points - Severe: 3 points

Question 29

Ascites Scores

Answer 29

- Absent: 1 - Mild-moderate: 2 - Severe-refractory: 3

Question 30

Bilirubin Scores

Answer 30

- <2 : 1 points - 2-3: 2 points - >3: 3 points

Question 31

Albumin Scores

Answer 31

- >3.5: 1 point - 2.8-3.5: 2 points - <2.8: 3 points

Question 32

INR Scores

Answer 32

- <1.7: 1 point - 1.7-2.3: 2 points - >2.3: 3 points