Chronic Liver Disease Flashcards
1
Q
Stimuli for stellate cell activation and transdifferentiation
A
- Chronic inflammation and associated cytokines
- Cytokines from Kupffer cells, endothelial cells, hepatocytes, and bile duct epithelial cells
- In response to change in ECM composition
- Direct stimulation by toxins
2
Q
Where is scar laid in fibrosis?
A
Usually in the space of Disse in a lobular pattern
3
Q
Liver fibrosis diagram
A
4
Q
Do patients with acute liver failure tend to get fibrosis?
A
No! Despite the presence of many of the same stimuli.
This may be related to the chromatin state of the stellate cells.
5
Q
In a fibrotic liver, there is an equilibrium between. . .
A
. . . fibrosis and regeneration.
The balance in active disease favors the former and with remission of disease the latter is favored.
However, once this progresses to full cirrhosis, it is irreversible.
6
Q
Cirrhosis
A
- The histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury that leads to portal hypertension and end stage liver disease
- Develops as a result of the combined effect of ongoing liver injury, hepatocyte death, scarring, and regeneration
7
Q
Histologic progression of liver fibrosis
A
8
Q
Effects of fibrosis on sinusoids
A
Defenestration of sinusoidal endothelial cells and ultimately sinusoidal constriction (increased intrahepatic vascular resistance)
9
Q
Splanchnic circulation
A
10
Q
Hepatic portal system
A
11
Q
Hepatic vasculature
A
- High-compliance, low-resistance system
- Accomadates a large volume following a meal without substantially increasing portal pressure
- The hepatic sinusoids are highly permeable because they lack a proper basement membrane and because the endothelial cells that line the sinusoids contain fenestrae
12
Q
Diagram of hepatic sinusoid layers in normal liver versus cirrhotic liver
A
13
Q
In the United States, ___ is by far the most common etiology of portal hypertension
A
In the United States, cirrhosis is by far the most common etiology of portal hypertension
14
Q
In cirrhosis, portal hypertension is the result of two major factors:
A
- Increased resistance to portal blood flow
- Increase in portal venous inflow
15
Q
Reasons for portal hypertension in cirrhosis
A
- Structural changes occur when there is distortion of the liver microcirculation by fibrosis, nodules, angiogenesis, and vascular occlusion in response to increases in flow and shear stress
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Contraction of activated hepatic stellate cells that surround hepatic sinusoids
- Too little Nitric oxide or too much Endothelin I can lead to increased resistance through the hepatic microcirculation
- Angiotensin II is a particularly strong constrictor of stellate cells and is increased abundance during cirrhosis due to systemic sympathetic hyperactivity
16
Q
Reasons for increased portal venous flow in cirrhosis
A
- Hyperdynamic circulation in cirrhosis is characterized by peripheral and splanchnic vasodilatation, and increased cardiac output to maintain near normal blood pressure.
- NO-mediated relaxation of splanchnic arterioles leads to splanchnic vasodilation and splanchnic hyperemia
- Result is increased flow into the portal system, exacerbating portal hypertension
17
Q
In cirrhosis, the picture inside the liver is characterized by ___ while the picture outside the liver is characterized by ___.
A
In cirrhosis, the picture inside the liver is characterized by vasoconstriction while the picture outside the liver is characterized by vasodilation.
18
Q
Categories of portal hypertension
A
- Pre-hepatic
- Intrahepatic pre-sinusoidal
- Intrahepatic sinusoidal
- Intrahepatic post-sinusoidal
- Post-hepatic
19
Q
Portal pressure gradient
A
- Pressure gradient between the portal vein and the IVC
- Normal range 1-5 mmHg
- The larger the gradient, the more severe the portal hypertension and the more likely complications of cirrhosis
- Hepatic Venous Pressure Gradient (HVPG) used as surrogate for portal pressure gradient
20
Q
Measuring pressures to assess portal hypertension
A
- FHVP = Free Hepatic Vein pressure: Balloon deflated in hepatic vein 2-4 cm beyond its connection to the IVC
- WHVP = Wedged HV Pressure (surrogate for portal pressure in cirrhosis): Balloon inflated and occluding in small hepatic veins
- HVPG= Hepatic Venous Pressure Gradient = the difference between the WHVP and FHVP. Represents the pressure gradient between the portal vein and the intra-abdominal IVC.
21
Q
HVPG range
A
- Normal 1-5 mmHg
- HVPG ≥10 mmHg is associated with varices
- HVPG >12 mm Hg is associated with a higher risk of variceal hemorrhage
22
Q
Causes of cirrhosis
A
- Hepatitis C
- Alcoholic liver disease
- NAFLD
- Hepatitis B
- Hemochromatosis
- Less common causes, including many autoimmune fibrosing disorders
23
Q
Physical findings of cirrhosis secondary to altered liver function
A
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Impaired estrogen metabolism and consequent hyperestrogenemia
- In male patients, palmar erythema (intense red coloration of thenar and hypothenar eminences, a reflection of local vasodilatation) and spider angiomas of the skin may develop
- Hypogonadism and gynecomastia
- Hypogonadism may also occur in women due to suppressed LH/FSH
24
Q
Clubbing in cirrhosis
A
Clubbing of the fingernails may result from the presence of arteriovenous shunts in the lung as a result of portal hypertension.
25
Jaundice pruritis
Jaundice, when chronic, can lead to pruritus the intensity of which can be profound. Some patients may even scratch their skin raw and risk repeated bouts of potentially lifethreatening infection
26
Splenomegaly in cirrhosis
**Any longstanding portal hypertension may cause splenomegaly**
The massive splenomegaly may secondarily induce hematologic abnormalities attributable to hypersplenism, such as **thrombocytopenia or even pancytopenia.**
27
Diagram of a cirrhotic male
28
Compensated vs decompensated cirrhosis
29
Development of ascites
30
Hepatorenal syndrome
* Cascade of events associated with **intense dilatation of the splanchnic arterial vasculature** in the setting of cirrhosis resulting in **_profound renal arterial vasoconstriction_** and **progressive renal failure**
* Excessive vasoconstriction **caused by RAAS and vasopressin**
* A type of **pre-renal state**
31
Sequence of events in hepatorenal syndrome
32
Paracentesis for ascites
* May be **diagnostic or therapeutic**
* Color alone may give important information - pus-like, brown, milky, bloody, or clear
* May be cultured, stained, or otherwise assayed for bacteria
* **Albumin level may be measured**
33
**Serum-Ascites Albumin Gradient** (SAAG)
* Test based on the balance of oncotic and hydrostatic forces
* In patients with portal hypertension, there is an abnormally high hydrostatic and oncotic pressure gradient, favoring ascites
* **Cirrhotic ascited fluid is a transudate, which is albumin poor**
* The SAAG will be **elevated (≥1.1 g/dL)** in any disorder in which **portal hypertension** is present.
* A **low SAAG (\<1.1 g/dL)** suggests that the capillaries and/or lymphatics are **disrupted or inflamed** (infections, oncologic conditions)
34
Spontaneous Bacterial Peritonitis
* An ascitic fluid infection without an evident intra-abdominal surgically treatable source
* Common complication of **cirrhosis and ascites**
* Translocation of **gut bacteria across the edematous intestinal wall into MLNs,** followed by **rupture of the infected lymphatics into the ascitic fluid**
* **Bacteria are almost always of GI origin**
* **Symptoms: Abdominal pain, fever, abdominal distension,** worsening hepatic encephalopathy or renal insufficiency
35
Collateral varisces that may be utilized when the portal system is backed up
36
Hepatic encephalopathy
* Increasing in serum ammonia due to lack of hepatic detoxification, causing neuropathy
* Manganese toxicity also plays a roll
* Astrocytes convert ammonia and glutamate into glutamine, which in turn acts as an osmolyte and increases cerebral volume
* May also occur when the liver is fully functional if there is significant porto-systemic shunting
* Brain edema may occur in conjunction with a rapid rise in ammonia levels, particularly in patients with no prior liver failure
* If unchecked, this may lead to coma, brain stem herniation, and death.
37
Hepatocellular carcinoma and cirrhosis
Cirrhosis increases risk of hepatocellular carcinoma. Even in individuals who begin to progress torwards cirrhosis, but then recover, the increased risk of hepatocellular carcinoma remains.
This is likely due to the cumulative exposure to growth factors.
38
Child-Pugh classification
* Used to assess the **surgical risk** in patients with cirrhosis
* Components include presence of ascites, bilirubin, albumin, INR, and degree of encephalopathy.
* Categorize patients into three categories: **well-compensated disease, significant functional compromise**, and **decompensated disease.**
* These correlate with 2-year-survival
39
Model for End Stage Liver Disease (MELD) score
* Liver disease severity scoring system
* **Uses serum bilirubin, serum creatinine, and INR**
* **Predicts three-month survival**, quite accurately
* Used to determine who is in **most urgent need of a transplant**
* New version is **MELD-Na** which **incorporates the serum sodium** into prognostication
40
Pediatric End-Stage Liver Disease (PELD) score
* For patients \<12 y.o.
* Uses age, bilirubin, albumin, INR, and history of growth failure to estimate 90-day waitlist mortality for pediatric liver transplant candidates
41
Health maintenance for patients with compensated cirrhosis
* **Surveillance for Hepatocellular carcinoma,** screening for **esophageal varices, minimizing alcohol consumption,** nutritional counseling, and physical therapy
* **Immunization** against HAV, HBV, pneumococcal pneumonia, and influenza
* Delaying cirrhotic development by treating underlying causes
* **NSAIDs should be avoided as they may provoke hepatorenal syndrome**
* Patients with cirrhosis have protein calorie malnutrition, and **frequent high-calorie small meals,** as well as **bedtime snacks**, are recommended
* **Fat-soluble vitamins and zinc** levels require monitoring, with replacement if required.
42
Is tylenol safe for patients with cirrhosis?
Yes, as long as they don't take too much.
In general, acetaminophen may be used in persons with cirrhosis in doses of **up to 2 g daily**
43
Fatigue in cirrhotic patients
A major factor in reducing a patient's quality of life and may be a manifestation of covert encephalopathy
44
Depression in cirrhotic patients
Depression occurs in 30% to 40% of patients with cirrhosis
45
Cirrhosis compensation and decompensation summary
46
Pringle Maneuver
47
Better portal vein diagram
48
Four major porto-caval shunts
49
Hepatic adenomas
50
Rex Meso-Portal Shunt
Surgical treatment for pre-hepatic pulmonary hypertension. Simply bypass the occluded vessel!
51
Porto-caval side-to-side shunt
Another surgical treatment for pulmonary hypertension. Risk for hepatic encephalopathy.
52
Central splenorenal shunt
Another surgical treatment for pulmonary hypertension. Risk for hepatic encephalopathy.
53
Transjugular intrahepatic porto-systemic shunt
Treatment for **intrahepatic** portal hypertension
54
Endoscopic mangement of esophageal varices
In urgent scenarios, endoscopy may be utilized to stop bleeding of esophageal varices and stabilize a patient so that consideration may be given prior to addressing the cause of their portal hypertension.
Importantly, this gives interventional radiologists enough time to obtain valuable data about the specific site of the lesion.
55
Spider angiomas
Related to hepatic insufficiency
56
Portal HTN with high gradient pressure is of ___ etiology.
Portal HTN with high gradient pressure is of **intrahepatic** etiology.
57
Portal HTN with low gradient pressure, but high free hepatic vein pressure and high wedge pressure is of ___ etiology.
Portal HTN with low gradient pressure, but high free hepatic vein pressure and high wedge pressure is of **post-hepatic** etiology.
58
Portal HTN with low gradient pressure, low free hepatic vein pressure, and low wedge pressure is of ___ etiology.
Portal HTN with low gradient pressure, low free hepatic vein pressure, and low wedge pressure is of **pre-hepatic** etiology.
59
When treating a patient with an upper GI bleed from ruptured varices, you should avoid . . .
. . . **over-transfusing.**
Putting too much blood in will increase the pressure and rupture more varices!
60
Octreotide
In addition to its other roles as a somatostatin analogue, it may act as a splanchnic vasoconstrictor, countering splanchnic vasodilation in cirrhosis.
For this reason it is useful for treating bleeds due to ruptured varices in the acute setting.
61
Varix banding
Endoscopic procedure where varix bleeds are suctioned into a tube, then clamped off with a rubber band. This stops the bleeding acutely.
In a matter of days, the blood will have clotted and the tissue will eventually slough off. A scar will form in this site, tightening it up and making it less likely to rupture again in the future.
62
Fibroscan
Type of routine test done to screen high-risk individuals for early signs of cirrhosis.
VERY early in this screening field and this will likely change dramatically within the next decade, but cirrhosis screening is a big topic of research right now.
Extensively utilized in obese individuals at risk for NAFLD-pathway to cirrhosis.
63
Sinistral Portal Hypertension
Localized, left-sided portal hypertension due to an obstruction in the splenic vein specifically.
Results in expanded short-gastric veins, but no other blood vessels. Risk for gastric varix rupture.
64
A major cause of AKI in decompensated cirrhosis is. . .
. . . **renal artery vasoconstriction**.
This is a **pre-renal problem that will not resolve by giving fluids**.
There is no direct kidney pathology! These patients recover **full kidney function when they receive a liver transplant.**
**This is the crux of hepatorenal syndrome.**
65
Primary biliary cholangitis
An autoimmune disease resulting in damage to small bile ducts.
Chronic damage over years results in fibrosis, precipitating cirrhosis.
