Liver I-usera Flashcards
1
Q
The (blank) is a location in the liver between a hepatocyte and a sinusoid. what is its function?
When can the function get impaired?
A
perisinusoidal space (or space of Disse)
allows for diffusion of nutrients
-in liver disease leading to obliteration of the space and decreased nutrient uptake and waste disposal by haptocytes.
2
Q
What cells does the space of disse contain?
What do they do?
If you get a bunch of insults to these cells causing inflammation, what can result?
A
Hepatic stellate cells
Store fat or fat soluble vitamins (like Vit A)
Stellate cells transform into myofibroblasts resulting in collagen 1 and 3production, fibrosis and cirrhosis
3
Q
What is a bile canalicuil?
A
how bile is connected throughout hepatocytes
4
Q
What blood supply am I talking about:
Venous blood rich in nutrients from the alimentary tract (60-70%)
A
Portal Vein
5
Q
What blood supply am I talking about:
Arterial blood rich in oxygen from the celiac axis (30-40%)
A
Hepatic artery
6
Q
What does the right hepatic vein drain?
What does the left hepatic vein drain?
What does the middle hepatic vein drain?
A
Drains right lobe
Drains left lateral lobe
Drains middle, left lobe and right lobe
7
Q
How does blood travel through the liver?
A
Portal vein-> central vein-> interlobular vein-> hepatic veins
8
Q
What is the portal triad?
A
Hepatic artery, bile duct, portal vein
9
Q
What is a hepatic lobule? What is this module for?
A
hexagonal unit oriented around central vein (hepatic vein) with portal vein around the periphery
-description of histopathology of the liver
10
Q
What does centrilobular area indicate?
A
area of the liver closest to the hepatic vein
11
Q
What does periportal area indicate?
A
area of the liver closest to the portal tract
12
Q
What is an acinus?
What does an acinus
A
triangular unit with the apex situated near the hepatic vein and the base formed by portal vein tract
13
Q
What do zones 1-3 indicate in an acinus?
A
zone 1 - closest to portal vein, most oxygenated
Zone 2 -middle
Zone 3- least oxygenated, closest to central vein
14
Q
The liver is vulnerable to a wide variety of metabolic, toxic, microbial, circulatory, and neoplastic insults.
T or F
A
T
15
Q
Liver disease is an insidious process in which clinical detection and symptoms of hepatic decompensation may occur (blank) afte the onset of injury
A
weeks to years
16
Q
(blank) tests detect abnormal liver function help confirm the presence of liver disease but do not define the cause.
A
Biochemical
17
Q
What tests detect hepatocyte integrity?
A
AST
ALT
Lactate dehydrogenase (LDH)
18
Q
What tests detect biliary excretory function?
A
- serum bilirubin (total, indirect, direct)
- urine biliurbin
- alkaline phosphatase
- Gamma glutamyl transpeptidase (GGT)
- 5-nucleotidase
19
Q
What tests detect hepatocyte function?
A
Albumin
Prothrombin time (PT)
Ammonia
20
Q
Indirect levels of bilirubin tell you about (blank).
Direct bilirubin tell you about (blank).
A
unconjugated bilirubin
conjugated bilirubin
21
Q
What is the earliest sign of liver damage?
A
coagulopathy (PT will tell you this)
22
Q
If you cant get ammonium you get (blank)
A
toxic encephalopathy
23
Q
What are the patterns of liver injury?
A
Inflammation (acute vs chronic) Intracellular "things" Necrosis Regeneration Fibrosis
24
Q
SInce the liver responds to injury in only a few different ways, there are common clinical syndromes that occur as a consequence of many different diseases, what are these?
A
Hepatic failure
Cirrhosis
Portal HTN
Jaundice/Cholestasis
25
What is the most severe clinical consequence of liver disease?
This results from loss of (blank)% of hepatic functional capacity.
hepatic failure
| 80-90%
26
What is the end stage point of ALL LIVER pathology?
Cirrhosis
27
What are the three categoreis that hepatic failure can be grouped into?
- acute liver failure
- chronic liver disease
- hepatic dysfunction without overt necrosis
28
What are examples of causes of acute liver failure?
Massive toxic overdose,
Massive infarct
Acute EBV w/ hepatic necrosis
29
What is the definition of chronic liver disease?
hepatic necrosis and inflammation are present for at least 6 months-> most common route with the endpoint as cirrhosis
30
What is the definition of hepatic dysfunction without overt necrosis? What are some examples of things that can cause this?
viable hepatocytes with an inability to perform metabolic function
-tetracycline toxicity, acute fatty liver of pregnancy
31
What is this:
| Liver failure associated with encephalopathy within 6 months after diagnosis
Acute liver failure
32
What is this:
| encephalopathy that develops within 2 weeks of jaundice
Fulminant acute liver failure
33
What is this
| encephalopathy that develops within 3 months of jaundice
sub-fulminant liver failure
34
What are the causes of acute liver failure?
drugs
toxins
infections
autoimmune
35
What are the drugs that cause acute liver failure?
acetaminophen, rifampin, isoniazid, MAOIs, Halothane
36
What are the toxins that cause hepatic failure?
```
carbone tetrachloride (used to be used in laundry mats)
mushroom poisoning (aflatoxin)
```
37
What are the infections associated with acute liver failure?
Hep A
| Hep B
38
What are the clinical signs of hepatic dysfunction?
```
jaundice
easy bruising (coagulopathy)
Hypoalbuminemia
Hyperammonemia
Hypoglycemia
Fetor hepatis (order of liver failure)
Hyperestrinism
```
39
What will hyperestrinism cause?
```
hypogonadism
gynecomastia
spider angiomas
palmar erythema
muscle wasting (shoulder girdle atrophy)
```
40
What are the complications of hepatic failure?
severe coagulopathy
encephelopathy
hepatorenal syndrome
multiple organ failure
41
What are the complications of portal hypertension?
esophageal varices
42
What are the compications of malignancy?
hepatocellular carcinoma
43
Why does hepatic encephalopathy occur?
When your liver is broken it cant get rid of toxic metabolites so they go to your brain
44
(blank) is due to poor renal perfusion and renal vasoconstriction. Is there intrinsic renal pathology?
What will your UA look like in hepatorenal syndrome?
hepatorenal syndrome
NO!
Urine is hyperosmolar, hyponatremic, no proteinuria
45
What is a disorder of neurotransmission in the CNS and neuromuscular system associated with elevated levels of ammonia?
hepatic encephalopathy
46
What are the signs and symptoms of hepatic encephalopathy?
- subtle behavioral disturbances to confusion, stupor, coma and death
- rigidity, hyper-refexia, asterixis
47
What is this:
| rena failure in patients with severe chronic liver disease with no intrinsic cause for renal failure.
Hepatorena syndrome
48
What is hepatorenal syndrome due to?
- Systemic vasodilation and decreased perfusion pressure
- Activation of the renal sympathetic nervous system from vasoconstriction of afferent arterioles
- Synthesis of renal vasoactive mediators
49
What characterizes cirrhosis?
fibrosis (vascular disruption lead to hypoperfusion)
nodular regeneration
parenchyma/functiona diruption
greenish pigmentation (from trapped bile)
50
WHy does fibrosis lead to cirrhosis?
because fibrosis blocks perfusion and leads to chronic ischemic state
51
What is the most common cause of cirrhosis? Explain the MOA behind this?
Where does the fibrosis begin?
alcoholic liver disease
toxic metabolite from alcohol damages hepatic stellate cells and turns them into myofibroblasts which deposit collagen 1 and 3
Central vein and progresses towards sinusoids resuing in perisinusoid fibrosis
52
What type of fibrosis is this:
deposition of types I and III colagen into spaces of Disse.
What is this faciliated by?
What is it due to?
```
Bridging fibrosis
Activation of stellate cells into myofibroblasts
-chronic inflammation
-cytokine production
-disruption of the ECM
-direct stimulation by toxins
```
53
What is this:
after injury, surviving hepatocytes regenerate as spherica nodules within the fibrous septa
What will this fibrous cause?
Parenchymal nodule formation
new vascular channels b/w portal vessels and hepatic veins
54
In parenchymal nodule formation, the resultant fibrosis will cause new vascular channels b/w portal vessels and hepatic veins. This will cause what problem with the hepatocytes?
- delivery of blood to hepatocytes will be compromised
| - hepatocyte ability to secrete into plasma is compromised
55
What is the result of architectura distortion?
diffuse parenchymal injury
| diffuse fibrosis
56
If you have distorted sinusoida architecture what will result?
increased resistance and portal HTN-> resulting in hepatosplenomegaly
57
What is this:
| An increase in pressure in the portal vein due to arterial pressures being imposed on the portal system
Portal hypertension
58
What are the prehepatic causes of portal HTN?
Obstructive thrombosis
Massive splenomegaly
Portal vein constriction
59
What are the intrahepatic causes of portal hypertension?
Cirrhosis
Schistosomiasis (common in Africa)
Massive fatty change
Diffuse granulomatous disease (military TB etc)
Nodular regenerative hyperplasia (chronic insults)
60
What are the posthepatic causes of portal hypertension?
Right sided heart failure
Constrictive pericarditis
Hepatic vein outflow obstruction
61
Portal HTN occurs at the levels of the (Blank) caused by increased resistance. WHat are causes of this increased resistance?
sinusoid
- Contraction of SMC
- myofibroblasts
- disruption of blood flow by scarring and formation of parenchymal nodules
62
Portal HTN can occur due to increase flow by hyperdynamic circulation. What are the causes of this?
-arterial vasodilation in the splachnic circulation which leads to increase venous efflux in the portal system
63
Why do you get ascites in portal HTN?
accumulation of serous fluid in the peritoneal cavity due to...
- sinusoidal HTN
- hypoalbuminemia
- thoracic duct overflow
- splachnic vasodilation and hyperdynamic circulation
64
In portal HTN, you have some much blood backing up in your liver where does the blood go and why is this terrible?
goes to the esophagus creating esophageal varices-> prone to rupture
goes to rectum-> hemorrhoids
falciform ligament and umbilicus-> caput mudase (periumbilical vein engorgement)
65
The rise in the portal system pressure leads to (blank) of blood flow.
reversal
| (i.e. portal to system) by dilation of collateral vesses and development of new vessels
66
A small fraction of unconjugated bilirubin is unbound and can cause (blank).
Is it soluble in water?
In high levels, what happens to the unconjugatd bilirubin?
toxic injury (kernicterus)
- insoluble
- it cannot be excreted in urine even when blood levels are high
67
Unconjugated bilirubin makes a tight complex with (blank) in serum.
albumin
68
```
Is conjugated bilirubin...
(water soluble/ water insoluble)
(toxic/ non-toxic)
what is it bound to?
What happens to excess?
```
water soluble
non-toxic
albumin
excreted in urine
69
Normal bilirubin levels are (blank).
| Jaundice is noticable when bilirubin levels reach (blank)
0. 3 – 1.2 mg/dL
| 2. 0- 2.5 mg/dL
70
What is this:
| when bili production exceeds hepatic clearance
jaundice
71
What are the causes of unconjugated bilribubin induced jaundice?
- overproduction (hemolysis)
- Gilbert' syndrome
- Impaired conjugation (UGT1A1)
72
How do you get excess production of unconjugated bilirubin resulting in jaundice?
high levels of Unconjugated Bilirubin overwhelm the conjugating ability of liver and then get hemolysed to cause jaundice
73
What is gilberts syndrome?
| When does this result in jaundice?
- lack of glucuronyltransferase (which conjugates bilirubin) so build up of unconjugated bilirubin.
- periods of prolonged fasting, chronic insults, stress
74
What are the two disorders of unconjugated bilirubin that cause impaired conjugation (UGT)?
```
Neonatal jaundice (babies doent make UGT for a little while)
Criglar-Najjar Types 1 and 2
```
75
Which Criglar-Najjar syndrome is more severe, type 1 or type 2?
Type 1- AR, severe
| Type 2- AD, less severe
76
What are the 2 causes of jaundice causes by increased conjugated hyperbilirubinemia?
- Rotor syndrome (AR)
| - Dubin-Johnson Syndrome (AR)
77
What is dubin johnson synrome?
What is the genetic problem?
Do you die from this?
defective secretion of bilirubin out of the liver-> results in black liver
absence of MRP-2 (transports bile out of the liver)
no
78
What are the two types of neonatal jaundice?
Physiologic jaundice
| Breast milk jaundice
79
What is physiologic jaundice?
mild unconjugated hyperbilirubinemia due to immature hepatic conjugation and excretion system.
80
What is breast milk jaundice?
bilirubin deconjugating enzymes in breast milk
81
Crigler-Najjar syndrome type I is a (unconjugated/conjugated hyperbilirubinemia) problem. How is it inherited? What is the defect in bilirubin metabolism? What is the clinical course?
- unconjugated hyperbilirubinemia
- autosomal recessive
- Absent UGT1A1 activity
- Fatal in the neonatal period
82
Crigler-Najjar syndrome type II is a (unconjugated/conjugated hyperbilirubinemia) problem. How is it inherited? What is the defect in bilirubin metabolism? What is the clinical course?
- unconjugated hyperbilirubinemia
- autosomal dominant with variable penetrance
- decreased UGT1A1 activity
- innocuous
83
Gilbert syndrome is a (unconjugated/conjugated hyperbilirubinemia) problem. How is it inherited? What is the defect in bilirubin metabolism? What is the clinical course?
unconjugated
autosomal recessive
decreased UGT1A1
Innocuous
84
Dubin-Johnson syndrome is a (unconjugated/conjugated hyperbilirubinemia) problem. How is it inherited? What is the defect in bilirubin metabolism? What is the clinical course?
- conjugated
- autosomal recessive
- impaired excretion of bilirubin glucuronides due to mutation in MRP2
- innocuous
85
Rotor syndrome is a (unconjugated/conjugated hyperbilirubinemia) problem. How is it inherited? What is the defect in bilirubin metabolism? What is the clinical course?
conjugated
- AR
- decreased hepatic uptake and storage
- innocuous
86
What is this:
pathologic condition of impaired bile formation and bile flows that leads to the accumulation of bile pigment in hepatic parenchyma
What is it caused by?
Cholestasis
Extrahepatic or intrahepatic obstruction of bile channels
Defection in bile secretion
87
Hepatocyte dysfunction or biliary obstruction results in (Blank)
cholestasis
88
What are the signs of cholestasis?
- Jaundice
- Pruritis
- xanthomas
- "silver stool"
- elevated alk phos
- intestinal malabsorption (vit A, D, K)
89
(blank) is defined as a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts.
Cholestasis
90
What are the causes of neonatal cholestasis?
- Bile duct obstruction
- Neonatal infection
- Toxic
- Metabolic disease
- Idiopathic neonatal hepatitis
91
Neonatal cholestasis is a result of prolonged (unconjugated/conjugated) hyperbilirubinemia.
conjugated hyperbilirubinemia
92
What bacterial infections can cause jaundice?
```
Extrahepatic infections (sepsis)
Staphylococcus aureus
Salmonella typhi (typhoid fever)
Treponema pallidum
Ascending biliary infections (cholangitis)
```
93
What parasitic infections can cause jaundice?
```
Malaria
Schistosomiasis
Strongyloidiasis
Cryptosporidiosis
Leishmaniasis
Echinococcosis
Liver flukes
```
94
What parasitic diseases can cause jaundice?
```
Echinococcal cyst
Clonorchis sinensis
Fasciola hepatica
Schistosomiasis
Malaria
strongyloides
```
95
(blank) is a parasitic disease of tapeworms of the Echinococcus type that infects the liver and causes jaundice.
echinococcal cyst
