1. HB Pathology Flashcards
Well show you how the liver exists for clearing synthetic funct. And well show how the biliary system exists to clear some of the bile.
Now the systems of the liver and the biliary system are actually composed of both hepatocytes, arterial branches (bring blood in), they’re composed of venous flow (venous blood from portal system that drains gut into liver). They are composed of outflow venous systems from liver. So blood goes in, mixes around and goes out.
Then biliary system which drains bile (combo of bilirubin derived from Hemoglobin and bile salts from cholesterol metabolism). And they drain outward toward liver into lumen of duodenum.
Note that the arterial branches of hepatic artery to the liver feed not only ____ as they mix
w venous blood in liver, but actually directly feed another sole vascular nutrient source of ____.
hepacytes
biliary system
Case 1- abnormal liver enzymes, on blood test, you think about diff processes that affect liver that give that presentation. Right off the bat its the vast ____ that have elevated or abnormal associated enzymes that truly have underlying liver disease. This is good news. Bad news: we have to figure out is that the case, if they do have liver disease, what is it?
Below: showing types of non neoplastic diseases well talk about. These may affect liver, txts may be very different. This is why knowing types of disease w in the liver esp for NON- neoplastic disease is v important cuz diff prognosis and therapeutic implications
Ex. Fatty liver disease. Whats the cause? ____ syndrome, altered diet, alcohol use. So consequences? W many chronic liver diseases may have ____, chriossis and impaired liver funct.
Ex. Viral Hep C. Chronic liver disease get fibrosis and chirroshis, treat w ____.
Ex. Autoimmune disease. May show similar liver enzymology and clinic presentation. You DONT treat w antivirals, use ____ suppression.
Point: figure out etiology of liver disease so you can understand prognosis and txt.
minority
metabolic
fibrosis
immune
Bottom Line: Liver
- Functions
- ____ (e.g. coagulation factors and albumin)
- ____/detoxify (e.g. bilirubin and drugs) Exogenous (drugs) and endogenous toxins (bilirubin)
- Disease States
- ____ dictate treatment and outcomes
- Acute (no risk fibrosis) versus Chronic (risk for fibrosis)
Rather than leave conclusion to end, shell start off w key points. reads bullets
In terms of inflammatory or non neoplastic states of liver make a point that we need to distinguish acute vs chronic!
Acute:
ALL acute liver injuries have no risk of ____ and no risk of subsequent going on to ____!
Cause NO problems long term, of synthetic and clearing; and no incr risk of ____.
Chronic:
have a risk for fibrosis, hence ____ hence can decrease funct. (both synthetic and learning)
All causes of cirrhosis increase risk of ____
synthetic
clearing
etiologies
fibrosis
cirrhosis
cirrhosis
hepatocellular carcinoma
Lesions and Neoplastic processes
- Inflammatory (e.g. abscess from bacteria)
- Benign (e.g. hemagioma)
- Malignant: the most likely tumor
- ____ (____ cancer) the most probable in a non-cirrhotic liver
- ____ the most probable in a cirrhotic liver
In terms of take away for neoplastic process in the liver aka mass lesions to be more inclusive, we can break down to these categories:
inflammatory
benign- no metastatic potential malignant
Most common malignant tumor in NON cirrhotic liver: is METASTATIC, COLON CANCER Most common malignant tumor in cirrhotic liver: hepatocllular carcinoma
Metastatic lesion to a chronic liver essentially doesn’t occur.
metastasis
colon
hepatocellular carcinoma
Bottom Line Biliary System
• Functions:
• ____ for bile to GI lumen
• Bile helps in ____ absorption and clearing toxins and other agents
- Diseases
- Mechanical: e.g. ____
- Developmental: e.g. Alagelieles
- ____: e.g. PBC, PSC
- Neoplastic: ____
• Mechanical
• Developmental
• Inflammatory
◦ PBC- primary biliary colangitis (used to be called primary biliary chirossis)
◦ PSC (primary sclerosing colangitis)- which is highly associated w ulcerative colitis
• Neoplastic-cholangiocarcinoma
◦ Unlike hepatocellular carcinoma, which Is associated w ALL causes of cirrhosis. The risk factors for cholangiocarcinoma are 3. Most common: ____.
‣ Second most common in US is ulcerative colitis w associated ____.
‣ Worldwide- most common cause are ____ flukes that live in biliary tree that can injure biliary tree. So prevalence of diseases depends where you live
conduit fat stones inflammatory cholangiocarcinoma
bad luck
PSC
liver
Liver: Functions • \_\_\_\_ • Hormone converter • OH \_\_\_\_ • T4\_\_\_\_ • Storage • Synthesizes
detoxification
VIT D
T3
Liver: Clearing
• Glutamate + NH4+ > ____ + H2O; transaminases; transport to kidney where ammonia excreted
• Liver gets rid of 1000 mmol/day of ____ groups generated from catabolism of amino acids
• Liver makes ____ (95% of all ammonia)
glutamine
amino
urea
Open abdomen. Liver composed of these things. Right lobe ____ in ____ abdominal quadrant.
larger
right upper
Bile & Blood Flow
Nice ____ consistency.
Portal tracks is where venous blood flow goes from portal vein and hepatic artery. They exit thought ____ vein
Bile runs COUNTER to vascular flow in liver, exits thru ____to duodenum.
homogenous
hepatic
bile duct
Liver histology
W closer power can see the liver actually has a CAPSULE. Capsule has nerve fibers. So if stretch liver quickly it ____to!
hurts
- Portal tract= portal triad (____, ____, ____)
* Sinusoids- where blood flows • Hepatocytes
vein
artery
bile duct
• Hepatic sinusoids or hepatic CORDS.
◦ Structured well to achieve funct of synthesis and clearing
◦ Hepatocyte- which is main engine of the process, it wants to have optimal exposure to
blood flow
◦ As such its aligned in terms of ____ celled cords, so on ____ sides has access to
blood flow. Separated by actual blood by____ cell, so not in direct contact w many cell in the blood, but certainly in terms of the ____ theres great even exchange.
single
both
fenestrated endothelial
The blood EXITS thru ____ aka central vein, which goes to the ____.
terminal venule
hepatic veins
Compartmental analysis
Liver is series of repetitive units: portal triad > blood flows, mixes from the ____ and ____ into the sinusoids. Exchanges w the hepatocytes, each green hepatocyte here is called the ____. Whereas the bilirubin is excreted there and then ultimately travels to bile duct and out to duodenum.
Exits via ____.
artery
vein
bile caniculus
terminal venule
Hepatocyte
Sub cellular compartments of ____ enzymes differs.
Elevated serum enzymes results from ____ post cellular injury.
• In terms of understanding elevated enzymes need to know what they are and how got elevated
• Liver associated enzymes are 3 fold
◦ AST- in ____
◦ ALT- ____ ONLY
◦ GGT- along ____
• Point: these have diff sub cellular compartments! So when have injury to hepatocyte can see patterns of elevation of enzymes based on subcellualr localization. Pattern and extent of elevation may give a clue of ____ of liver disease. When measure in blood liver ass. Enzymes, measuring blebs of hepatocytes that go into blood stream
enzymes
cytoplasmic blebbing
mitochondria
cytoplasm
canaliculus
etiology
When we measure the enzymes, we can say if we have an elevation of:
• ALT- that its most likely from ____.
• GGT- this is liver but more importantly injury processes of ____ system!
• AST- from liver BUT alot in other ____
• LDH elevation- never only ____! Think about other ____, lymphomas or leukemia
Know the organ compartments important to understand how to evaluate elevations!
liver biliary organs liver organs
Outline • Acute versus chronic injury • Patterns of injury and liver associated enzymes • Vascular • Hepatitic • Infiltrative • Cholestatic All may give ACUTE or CHRONIC injury: KEY is \_\_\_\_
- In terms of injury, wants to stress distinguish acute vs chronic
- Given either you can talk about patterns of injury to give clues to etiology.
- Doesnt read rest
etiology
Approach
A. acute versus chronic & outcomes
B. compartments of injury
• In terms of distinguishing acute vs chronic, thats important first thing you do ◦ Acute- complete ____ or die or get liver transplant
◦ Chronic- percolates along and may go to ____ and cirrhosis
• When think in terms injury, think compartment injured
◦ ____, biliary system, ____ system, etc
recovery
fibrosis
hepatocytes
vascular
Acute Injury May Result in Loss of Hepatocytes
Huge ____ capacity
Re-entry from ____ phase
• ACUTE
◦ Liver has yugeee regenerative capacity. Acute injury- the liver hepatocytes injured, die, but
cuz regenerative capability of hepatocytes that can re renter DNA syntheses-> regeneration. ◦ These no risk for more ____ disease assuming cause of acute injury gone.
regenerative
G0 into S
liver
Chronic Injury May Result in Fibrosis
◦ In contrast, liver injuries like Hep C, B, autoimmune Hepatitis that are ____ liver injury have propensity to cause fibrosis–> cirrhosis (disruption of hepatocellular architecture by fibrosis w associated regenerative nodules)
◦ Gross liver- ____
◦ ____- see what cirrhosis looks like, biopsy gold standard to make dx of cirrhosis cuz
NOT all nodular livers are ____!
◦ why care about cirrhosis? .. next slide
chronic
nodular
histo
cirrhotic
Consequences
- Portal hypertension
- Pressure = Flow X ____
- Varices: bleeding
- Ascites
• Increased risk of ____
- Decreased function
- Synthetic
- ____
- Edema
- Clearing
- ____
- Altered drug metabolism
Portal hypertension
• Portal vein into liver, fibrosis increases ____ in liver! Therefore cuz portal flow maintained the pressure goes up in portal venous system
• Veins draining into portal system increase, like in lower esophagus. As a consequence of inc pressure–> expand aka ____
◦ Decrease the synthetic funct of the liver (coagulation factors) my have propensity to bleed–> death
◦ Cuz of fluid dynamics in the liver, one can have ____ (fluid in abdomen cuz of portal hypertension)
• Incr risk hepatocellular carcinoma
• Dec funct
◦ Synthetic factors: albumin synthesis
◦ Clearing- big issue cuz not cleaning endo.exogenous things–> ____ ◦ All of these can cause death.. and death is bad.. who knew.
resistance
HCC
coagulopathy
encephalopathy
resistance
varices
ascites
encephalopathy
Stage
• How does cirrhosis occur? Very predictable pattern. Use trichrome stain.
• Normal- blue- mature collagen.
• Injuries:
◦ ____- of the portal Tracks in the collagen matrix
◦ 2 triads can connect and ____
◦ Ultimately get to cirrhosis
• Point- ____ incited by large variety of chimeric liver injuries
expansion
bridge
progressive
Mechanisms and Results of Injury
When think about liver injury, this is is what she thinks.
• Series of ways injure the liver (A B C D). They can give set of presentations either lab data or
clinical (Y Z B)
• Sometime liver injury A only give Y presentation but alot of times the same injury may give
multiple ____ and vise versa
• It can be quite overlapping but are ways to think about in terms of consequences and set Y Z W
that we can classify in terms of patterns of injury
• Reason for classifying in this fashion is cuz it’ll narrow down possibilities of inciting agent. Even
given agent, also have to distinguish bet acute and chronic injury
• All these patterns can be acute OR chronic liver process
presentations
• See again blood in and various flows inside
• Caudate lobe- has independent ____
drainage to Inferior vena cava
• Can drain out thru ____ veins
venous
hepatic
Venous Outflow Obstruction: Acute
- now bock blood flow OUT
- Can happen from: clot in IVC, right sided heart failure (putting pressure on liver)
- What happens? Liver ____. Blood in can’t get out
- Initial: increase ____ BUT…..
- But… w increased mechanical pressure can start to incite ____ RESPONSE (shell show later what looks like)
- After acute blockage get congestion in the liver here that show in histo
- In gross section: ____ LIVER- sign ____ congestion in liver
swelling size fibrogenetic nutmeg passive
Venous Outflow Obstruction: Chronic
“Cardiac Type Fibrosis” (NOT cirrhosis)
as a response to that pressure alone, a ____ response may ensue.
• Therefore see trichrome stain w increased collagen along the pressure gradient which will start fundamentally most increased pressure in the area of ____! Cuz if think about a stream w a damn, thats where the greatest pressure head is and eminates out from there.
• Reticulin stain (A)- this is silver stain (name not important) just hilights some of size of ____. And what she shows in conjunction w the increases pressure w fibrogenetic response get ____ of hepatocytes. atrophy due to pressure alone. Overall- ____ response and ____.
fibrogenetic terminal venule hepatocellular cords thinning fibrogenetic atrophy
- Now fundamentally see this alot of times pt w ____ disease.
- Interestingly cuz of livers tremendous ability and redundancy it RARELY leads to synthetic and clearing funct. BUT could get portal hypertension cuz reasons said before.
- Over time get fibrosis and it’ll affect whole liver
cardiac
- Here let’s block the hepatic veins
- What happens? Same thing. Initially liver ____ and if thats blocked acutely can swell acutely causing pain
- But the right and left hepatic lobes are still blocked so they’ll undergo same ____ like situation w cardiac disruption
- BUT cuz of the CAUDATE LOBE w the INDEPENDENT ____ drainage directly to IVC can escape the increased pressure and therefore doesnt undergo ____ or increased pressure it, actually gets ____
- She loves liver cuz socially conscious system in sense of when it senses the loss of parenchyma of brothers and sisters it gets bigger and makes more hepatocytes to ____ for loss of other lobes
swells fibrosis venous fibrosis larger accomodate
Venous Outflow Obstruction: Chronic
Budd-Chiari
- The ____ globe can become very enlarged. When you get the atrophy and fibrosis of other lobes of liver
- This state has a name: BUDD- CHIARI
- initially= acute but over time w fibrosis its chronic
- Caudate lobe enlarged and atrophy and fibrosis of rest of lobes
- In contrast to what stressed before, it does NOT meet the histologic definition even tho theres fibrosis in these lobes and in the cardiac? situation, it does have ____ nodules so it does NOT see the definition of cirrhosis
- Therefore in some ways accordingly, both the cardiac fibrotic state in these venous outflow and Budd- chair states do NOT have an increased risk of ____
- this is one ex. of fibrotic state without incr risk of carcinoma, and number 2, an amazingly interesting scenario where by shows us that ____ pressure alone in the liver–> fibrogeneic response NOT dependent on ____ mediators
caudate regenerative HCC mechanical inflammatory
Inflow Obstruction
What I we blocked inflow?
• Can get ____, looks like it would anywhere else in body
• To have infaraction in liver which is just decrease blood flow in, takes work. Why? Just like lung, it has a ____
BLOOD SUPPLY (venous and arterial)
• To get infarct need to disrupt ____ blood flows, but it can happen
• You have ____ necrosis of hepatocytes, important feature! Cuz if see that means there was ischemic
injury process.. seen on next slide
infarct
dual
both
coagulative
What If use block venous inflow?
Portal vein thrombosis
• This is an autopsy, but it didn’t die cuz of portal vein thrombus
• Initially nothing may ____! You could be fine in terms of function cuz live
off ____ artery
• It wont cause infarction, shows dual blood supply
happen
hepatic
• However, over time the clot in the portal vein may ____ w in the portal tracks w in the liver and you can get the clot and then w organization of the clot may obliterate the____ branches w in the liver in its entirety
propagate
portal venous
Portal Tract Venopathy
• And if that happens you get PORTAL TRACT ____ (said she doesnt care about the name…lies)
• You dont see the vein here, you’ve obliterated the organize w the____
• think about it, what will happen to pressure in portal system? GO ____
◦ Cuz increased resistance. Like taking a straw and decrease orfice of straw so harder to breathe through
• So you’ll have portal hypertension but it does NOT cause fibrosis in rest of the parenchyma, so NOT get ____
• this is ex. of how you have portal hypertension without cirrhosis!
• Worldwide what else can have that will lodge in a portal vein?
◦ one of major causes of portal hypertension in world is NOT hep B C, cirrhosis, its ____ (are these parasites that live in portal vein and mate and shed eggs into system, as eggs go up to portal venous system it CLOGS the portal vein)
• Portal hypertension is not a risk factor for ____ and doesnt cause ____ (google- A cancer in the slender tubes that carry the digestive fluid bile through the liver) cuz its not living in ____ tree (they have diff organisms)
venopathy
clot
up
cirrhosis
schistosomiasis
hepatocellular carcinoma
cholangiocarcinoma
biliary
• What if block artery?
Bile Duct Infarction
• Because of dual blood supply the ____ will be fine!
• However cuz bile duct nourished solely by hepatoarterial component, the ____
can have infarction if block some of hepatic arterial blood flow
• Here infrarcted bile duct, it can get so infarcted that ____ oozes out
hepatocytes
bile duct
bile
“Hepatitis” • Definition: • Acute • Chronic • Etiologies: • Viral (e.g Hepatitis A \_\_\_\_, Hep C \_\_\_\_) • Autoimmune • Toxins • Other • Pathology and Mechanisms of Disease • Etiology dependent
• Hepatitis- when she says hepatitis patterns of injury, talking about those lier processes aimed at hepatocyteS, aimed at diff pathogenies and etiologies
• Ex. Think about it in categories
◦ Viral- hep B and C are ____, hep A- affects hepatocytes and dmg but
ALWAYS ACUTE NEVER CHRONIC
◦ Autoimmune ◦ Toxins
acute
chronic
chronic
Hepatitis C: Chronic Injury • \_\_\_\_ Virus • NOT incorporated into host \_\_\_\_ • 85% of people infected go on to chronic \_\_\_\_ • Cirrhosis may follow • \_\_\_\_ are relatively ineffective
• May mount antibodies to virus, unfortunately those ab are ineffective at clearing
virus cuz of amazing high ____ role (envelope proteins help it escape
immune surveillance)
• Unfortunately theres NO ____ currently available to help hep C, unlike Hep B
where vaccines v effective and hep B is DNA virus
• Unlike hep B where minority get chronic liver injury, hep C for majority is
____ liver injury.. once you get it you have it. So may get fibrosis and cirrhosis
RNA
genome
hepatitis
antibodies
immunogenic
vaccines
chronic
• How does it give a hepatic pattern of injury?
• Hep C and B actually infect and live in the hepatocytes themselves, they mount immune response and the response is ____
• B and T cells go to portal tracts
• T cells go on to parenchyma, ID the infected hepatocyte and try to kill it to rid the body of the
infection
• It does it thru ____
• So see portal tract lymphocytic infiltrate
• Enzymatically- enzymes rich in liver, and hepatocyte itself- ____ and ____
• Bile caniculus may have slight elevation But not too much cuz its not part of the liver cell thats
injured w the viral hep C
• To get increased GGT you need synthesis of GGT by the hepatocyte that occurs only in certain
situation that occurs in some biliary types of injury
cell mediated
apoptosis
ALT
AST
Terminology for Chronic Hepatitis
- Limiting Plate
- Interface hepatitis 3. Activity
- Stage
• Talk about nomenclature of chronic hep.
• Applies to the Hep B, C, and autoimmune hep
• Things we talk about are the activity, or how many lymphocytes there are limiting the hepatocyte,
thats one feature and the other is ____ (something?) fibrosis
• Why do we care? Care about fibrosis cuz of reasons said, but the activity is somewhat loosely
associated w the probability and time course going onto fibrosis and cirrhosis
stage
