Disorders of the Liver Part 1 Flashcards
1
Q
What are the 4 lobes of the liver and what separates them?
A
- Anteriorly: Right lobe and left lobe by falciform ligament.
- Posteriorly: Anterior and posterior caudate via porta hepatis
2
Q
What are the 3 components of the porta hepatis?
A
- Hepatic portal vein
- Hepatic artery
- Common Hepatic duct
Not the same as a portal triad
3
Q
What are the two vessels that supply hepatocytes?
A
- Venous blood via portal vein
- Oxygenated blood via hepatic arteries
4
Q
What is the flow of blood beginning at a portal vein?
A
- Portal veins
- Sinusoids
- Central Veins
- Hepatic Veins
- IVC
5
Q
What two lipoproteins are made by hepatocytes?
A
- VLDL
- HDL
6
Q
What is bilirubin from?
A
End product of the breakdown of an RBC, created as unconjugated/indirect/lipid soluble bilirubin
Breakdown of heme to protoporphyrin to bilirubin
UCB = unconjugated bilirubin
7
Q
What binds to UCB and takes it to the liver?
A
Albumin
8
Q
What enzyme is used to conjugate bilirubin?
A
Uridine glucuronyl transferase = UGT
9
Q
What happens to bilirubin once it is conjugated?
A
- Transported down bile canaliculi to bile ducts
- Deposited within the gallbladder at direct/conjugated bilirubin
It is now water soluble.
10
Q
What converts CB to urobilinogen and what happens to it?
A
- Microbes convert it to UBG.
- UBG can either become stercobilin into your poop (giving it color)
- It can also become urobilin and get excreted via the kidneys or goes back to the liver
11
Q
What is jaundice?
A
- Product of heme metabolism
- Accumulation of bilirubin
12
Q
How elevated is serum total bilirubin to give skin a yellow discoloration?
A
Usually greater than 2.5mg/dL
13
Q
Would pre-hepatic jaundice present with higher UCB or CB?
A
UCB
14
Q
How do bilirubin levels look in pre-hepatic jaundice?
A
Increased UCB in serum due to RBC hemolysis
aka hemolytic anemias
15
Q
How can bilirubin levels vary in hepatic jaundice?
A
- Increased UCB in serum due to hepatocyte impairment
- Increased CB in serum due to hepatic duct obstruction
16
Q
How do bilirubin levels look in post-hepatic jaundice?
A
- Increased CB in serum due to biliary tract obstruction
- Decreased bilirubin in gut = pale/acholic stool and no UB in urine
17
Q
What clinical findings are most suggestive of elevated UCB?
A
- Normal stool and urine color
- Mild jaundice
- No bilirubin in urine
- Splenomegaly (Except in SCD)
18
Q
What clinical findings are most suggestive of elevated CB?
A
- Pruritis and jaundice
- Light colored stools
- Malaise, anorexia, low-grade fever, RUQ, Dark urine
- Hepatomegaly, spider telangiectasias, palmar erythema, ascites, gynecomastia, sparse body hair
- Varies based on liver dysfunction
19
Q
What is the term for light colored stool?
A
Acholic stool
20
Q
What clotting factors are NOT affected in liver disease?
A
- III
- IV
- VIII
21
Q
What does Vit K require to be absorbed from the GI tract?
A
Bile
22
Q
What CBC count will be lower in liver disease?
A
Thrombocytopenia
TPO is made in the liver
23
Q
What are the 3 common CBC abnormalities seen in liver disease?
A
- Thrombocytopenia
- Leukopenia
- Anemia
EPO is made in both the kidneys and liver
24
Q
What carrier protein does the liver make?
A
Albumin
25
What is the underlying mechanism behind portal HTN?
Blockkage in blood flow through the liver, resulting in **cirrhosis most commonly.**
26
What is the gold standard to diagnose portal HTN?
IVC catheter to measure hepatic venous pressure
27
What are the clinical manifestations of portal HTN?
* Splenomegaly
* Esophageal varices
* Hemorrhoids
* Caput Medusae
28
What are the main veins implicated in portal HTN?
* Esophageal veins
* Paraumbilical veins
* Superior mesenteric veins
* Inferior mesenteric veins
* Middle rectal veins
* Inferior rectal veins
29
What are the ABCDEs of Portal HTN?
* Ascites
* Bleeding
* Caput Medusae
* Diminished liver function
* Enlarged spleen
30
What is the MCC of ascites?
Cirrhosis
31
What are the underlying mechanisms of ascites?
* **Underfill** due to lack of albumin and shift of fluid
* **Overflow** due to increased pressure
* **Impairment** of RAAS
32
What is the MC organism that causes spontaneous bacterial peritonitis?
E. Coli
33
Why does hepatorenal syndrome occur?
1. Arterial vasodilation in **splanchnic circulation** due to Portal HTN
2. More NO is made, vasodilating more and causes a fall in CO
3. Kidneys become poorly perfused
4. Acute renal failure ensures
34
What causes pruritis in liver disease?
Bile salts
35
What are spider nevi and palmar erythema due to?
Excess estrogen
36
What can happen specifically to males with liver disease? Females?
* Males: testicular atrophy & gynecomastia due to **impaired cholesterol synthesis**
* Females: Menstrual irregularities due to **excess estrogen**
37
What is the severe manifestation of liver disease?
Hepatic encephalopathy due to **buildup of ammonia**
| Confusions, tremors, coma
38
What are the components of a LFT/hepatic panel?
* Total protein
* Albumin
* Total bilirubin
* Direct bilirubin
* AST/SGOT
* ALT/SGPT
* ALP
* **GGT**
* **PT/PTT**
* **Cholesterol**
* **BUN**
* **Hepatitis Panel**
| **Bolded** are addons
39
What are the two serum aminotransferases?
* Alanine aminotransferase (ALT/SGPT)
* Aspartate aminotransferase (AST/SGOT)
40
What liver enzymes measure hepatocyte damage?
* AST/ALT
* LDH
41
Which liver enzyme is most specific for hepatocellular damage if markedly elevated?
ALT
| AST is found in heart and skeletal muscle too.
## Footnote
ALT has a L, so its the most Liver specific
Acute Liver Trouble
42
What do significant elevations of ALT and AST associate the most with?
Hepatocellular damage
| 8-25x = acute damage
43
In general, what does an acute liver damage present as in terms of the aminotransferases enzymes? Chronic?
* Acute: ALT > AST (8-25x ULN)
* Chronic: AST > ALT (< 8x ULN)
| ALT = Acute Liver Trouble
44
What does a moderate elevation of AST > ALT of around 2 or more suggest?
Chronic alcoholic liver disease
45
What does a moderate elevation of AST > ALT of around 1-1.99 suggest?
Chronic NASH/non alcoholic cirrhosis
46
What elevates LDH?
Any cellular damage in general. Non-specific test.
47
What liver enzymes are used to measure cholestasis?
* **ALP**
* **GGT (both)**
* 5'-nucleotidase (liver specific)
48
What does a elevation of **ALP > 4x ULN** suggest? **< 4x ULN**?
* **More than 4x ULN = hepatic cholestasis**
* Less than 4x ULN = non-hepatic/non-cholestatic cause
49
What might elevated ALP and GGT suggest?
Hepatobiliary obstruction
50
What is one of the first enzymes to increase in an obstructive disease of the biliary tract?
ALP
51
What might elevated GGT without elevated ALP suggest?
Alcohol or medications
52
What is GGT not elevated in?
Bone disease
53
What LFTs suggest hepatocellular damage?
* Marked elevation of AST/ALT compared to ALP
* Elevated total and direct bilirubin
54
What LFTs suggest obstructive disease of the liver?
* Elevated ALP compared to AST/ALT
* Elevated GGT
* Elevated/normal total bilirubin
* Elevated direct bilirubin
55
In summary, what does elevated direct bilirubin suggest?
Hepatobiliary disease
56
What are the tests for hepatic synthetic function?
* Albumin
* PT
57
What affects albumin level?
* Liver damage
* Poor nutrition
* Kidney disease causing increased excretion(Nephrotic)
58
If PT is prolonged but LFTs remain normal, what does this suggest?
Liver function is fine and **not the cause**
59
What characterizes autoimmune hepatitis?
**Circulating auto-antibodies** and **elevated serum globulin levels**
60
What demographic is autoimmune hepatitis MC in?
Young to middle aged women
61
How does autoimmune hepatitis present?
* Insidious onset
* **Often precipitated by a viral illness/drug exposure or postpartum**
* **Otherwise healthy** with multiple spider nevi, cutaneous striae, acne
* **Extrahepatic features** like arthritis or thyroiditis
62
What lab findings are associated with autoimmune hepatitis?
* AST/ALT elevations of 1.5x-50x ULN
* Elevated total bilirubin
* Positive ANA
* pANCA
* **Anti-SLA (soluble liver antigen)**
63
How is autoimmune hepatitis definitively diagnosed?
Liver biopsy
64
What conditions are autoimmune hepatitis co-existing with sometimes?
* Primary biliary cirrhosis
* Sclerosing cholangitis
65
How do we treat autoimmune hepatitis?
* **Prednisone**
* May add azathioprine
* Liver transplant last resort
66
What medications can induce hepatitis?
* Acetaminophen with alcohol
* Isoniazid with rifampin
* ABX (tetracyclines)
* Herbal supplements
67
How does drug/toxin induced hepatitis present?
* Hepatomegaly
* Jaundice
* Fatigue
* N/V
68
How do the transaminases present in drug/toxin induced hepatitis?
ALT > AST
| Acute Liver Trouble
69
How much acetaminophen can cause hepatitis?
4g in adults or 80mg/kg in kids
| Found in more than just tylenol!!!!!!
70
When does stage 1 of acetaminophen induced hepatitis occur and what happens?
* Timing: 30 minutes - 24 hours
* N/V, diaphoresis, pallor, lethargy, malaise
* Normal labs
* Could be asymptomatic
71
When does stage 2 of acetaminophen induced hepatitis occur and what happens?
* Timing: 24-72 hours
* Stage 1 symptoms resolve, but then the patient worsens
* AST/ALT elevations occur
* **RUQ pain with hepatomegaly and tenderness**
* PT and bilirubin elevations
72
When does stage 3 of acetaminophen induced hepatitis occur and what happens?
* Timing: 72-96 hours
* Stage 1 symptoms reappear + **hepatic encephalopathy**
* AST/ALT > 10k
* Prolong PT/INR
* **Hyperammonemia**
* Hypoglycemia
* Acute renal failure
* **Death usually occurs d/t multi organ failure**
73
When does stage 4 of acetaminophen induced hepatitis occur and what happens?
* Timing: 4 days to 2 weeks
* **Only occurs if you survive stage 3**
* If you do recover, **complete recovery is seen**
74
How do you diagnose acetaminophen induced hepatitis?
* Serum level of acetaminophen
* **treat above the line for the graph**
75
How do you treat acetaminophen induced hepatitis?
**N-acetylcysteine**
| Activated charcoal also helps
76
What is considered excessive alcohol intake and how long do you have to do it for have high risk?
* Males: 2+ drinks a day
* Females: 1+ drinks a day
* 10 years of this
77
What are the stages of alcoholic liver disease?
1. Fatty liver/steatohepatitis (**hepatomegaly**)
2. Alcoholic hepatitis (**acute/chronic inflammation and parenchyymal damage**)
3. Cirrhosis (**Non-reversible**)
78
How much do you have to drink to have a higher frequency of alcoholic liver disease?
50g of alcohol daily for 10 years
79
Why does alcohol cause damage?
Acetaldehyde is a metabolite of ethanol that causes cellular damage
80
In steatohepatitis, how do labs look?
* Mild AST/ALT elevations
* Macrocytic anemia
81
In alcoholic cirrhosis, how do labs look?
* AST/ALT elevations
* Elevated total bilirubin > 10mg
* Hypoalbuminemia
* PT/INR prolongation
* Anemia (iron and folate)
* Later: Lyte abnormalities and elevated BUN/Cr
82
In alcoholic hepatitis, how do labs look?
* **AST > ALT by 2x or more**
* ALP elevated up to 3x
* Elevated total bilirubin
* Leukopenia and thrombocytopenia
| Not an acute process, so AST elevates more
83
How do you definitively diagnose alcoholic liver disease?
Biopsy showing macrovesicular fat and PMN infiltration with hepatic necrosis
84
How do alcoholic steatohepatitis and NASH present?
Identical
85
What is the #1 treatment for alcoholic steatohepatitis?
Not drinking
| Reversible at steatohepatitis stage.
86
What are the pharmacotherapy options for alcoholic hepatitis?
* Methylprednisolone x1 month
* Pentoxifylline if severe (vasodilator) x1 month
87
What are the unfavorable prognostic factors for alcoholic hepatitis?
* Prolonged PT/PTT
* Bilirubin > 10mg
* Hepatic encephalopathy
* Azotemia
88
What is the MC risk factor for NA fatty liver disease?
Obesity
89
What is the difference between Non-alcoholic fatty liver and non-alcoholic steatohepatitis?
* NAFL has **NO inflammation**
* NASH has **inflammation**
90
When is NAFLD typically diagnosed?
40s-50s
91
How do AST/ALT appear for NASH?
< 2
| ETOH would make it higher
92
How do you definitively diagnose NASH?
Liver biopsy
93
NAFLD Spectrum Image
94
What medications can help treat NAFLD?
* Vit E
* TZDs
* Metformin
* Wt loss agents
## Footnote
Insulin sensitizing agents
95
What are the poor risk factors for NASH to become cirrhosis?
* Old
* Male
* Obesity
* DM
96
What is seen throughout the liver in cirrhosis?
* Fibrosis
* Nodular regeneration **replacing functional hepatocytes with nonfunctioning fibrotic nodules**
97
How does cirrhosis typically present?
* N/V
* Abd pain
* S/S of Portal HTN
* Spider angiomas, palmary erythema
* Menstrual abnormalities, ED, gynecomastia
* Anemia
* Glossitis
* Jaundice (later)
* Ascites (later)
* Encephalopathy (later)
98
How do labs appear early in cirrhosis?
Minimal changes
99
What is the first-line test for cirrhosis?
**US** to assess size and ascites and other stuff
100
How is cirrhosis definitively diagnosed?
Liver biopsy
101
What other imaging is highly useful in cirrhosis evaluation?
EGD to check for esophageal varices
| Since Portal HTN is v common w/ cirrhosis
102
How do we treat ascites/edema?
* Na restriction
* Spironolactone
* Lasix
* Paracentesis (new onset, unable to tolerate diuretics, or respiratory issues)
* TIPS placement for variceal bleeding, but also treats ascites
103
What suggests bacterial peritonitis from ascites?
* Worsening abd pain
* Fever
* Leukocytosis
104
What is the MCC of bacterial peritonitis and the treatment and prophylaxis?
* MC organism: **E. coli**
* Tx: **Cefotaxime 2g** IV q8-12h x 5-7d
* Prophylaxis: **Oral FQ**
105
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What secondary organ system can be affected by liver disease?
Renal
106
How do you treat hepatic encephalopathy?
* Less protein
* **Lactulose** to get rid of ammonia organisms
* ABX (Rifamixin or metro)
107
What infusions may help with anemia and coagulopathies due to cirrhosis?
* Ferrous sulfate
* Folic acid
* Vit K
* FFP
* Oral thrombopoietin (maybe)
108
What are the components of a MELD score and what is it?
* Model for End Stage Liver Dz
* Bilirubin, creatinine, and INR
* **14 or higher needed to qualify for transplant**
109
What everyday things can help reduce the risk of rapid decompensation from cirrhosis?
* Coffee
* Tea
* Statins
110
What is primary biliary cirrhosis/cholangitis?
Chronic, autoimmune destruction of **intrahepatic bile ducts and cholestasis**
111
Who is primary biliary cholangitis MC in?
Women aged 40-60
| Often with other autoimmune conditions
112
What lab finding is incidentally found that suggests primary biliary cholangitis?
Elevated ALP
113
What are the MC early s/s of primary biliary cholangitis?
Fatigue and pruritis
114
What labs are elevated in primary biliary cholangitis?
* Early: ALP and cholesterol
* Later: Bilirubin
* Antimitochondrial Ab in 95% of pts
* Positive ANA and IgM
115
How is primary biliary cirrhosis diagnosed?
US and labs only
116
What is the treatment for Primary biliary cholangitis?
* Ursodeoxycholic acid (FDA approved)
* For itchin: Cholestyramine (bile salt binder)
117
What does primary biliary cirrhosis increase your risk of?
Hepatobiliary carcinoma
