Hepatobiliary Disease Flashcards
Structure and Function of the Liver
The liver is located in the (1) quadrant of the abdomen in the ______ space just below the right side of the _____ and under the ___ cage.
It is anatomically separated into ___ predominant lobes, a right and left lobe.
Function =
(1) large ligaments that separate the right and left lobe
(1) ligament on the bottom of the liver
(1) large vein that drains all the blood from lower limbs and carries it to the heart - liver empties directly into this
(1) structure connected to the liver
Right upper quadrant, peritoneal, diaphragm, rib cage
Two lobes
One of our major filtering organs
Falciform Ligament
Round Ligament
Inferior Vena Cava
Gallbladder
Blood Flow Through the Liver
The liver recieves __% of cardiac output on average.
Blood enters the liver through two vessels
- (1) carries blood from the GI tract directly to liver and is critical for liver to carry out all of its _____
- (1) functions to _______ the liver
These vessels converge and blood ____ as it passes through the hepatic _____ toward the ____ veins
The central veins drain into the _____ vein which then leads to the (1)
25%
- Portal vein, functions
- Hepatic artery, oxygenate
blood mixes, hepatic sinuses, central veins
hepatic vein, inferior vena cava
Blood Flow Through Liver (Notes)
Blood flow through the liver is very unusual - one of the only places we see venous and arterial blood _____
Portal vein: blood that enters this carries everything that was absorbed in the (1) - so that blood is critical for liver to carry out all of its _____
Hepatic Artery: branches off the (1) - ______ the liver
Flow of Blood =
Each of the hexagonal arrangement of cells is the _____
mixing
GI tract, functions
Abdominal aorta, oxygenates
Blood coming from GI tract -> portal vein -> hepatic sinuses -> mixes with arterial blood and passes through hexagonal arrangement of liver cells (hepatocytes) -> drains into central vein -> hepatic vein -> inferior vena cava
Filter
Hexagonal Arrangements of Hepatic Lobules
Hepatic Lobule =
- Hepatic Triad =
Blood moves into the hexagon: You can see the mixing of blood from hepatic artery (_____ blood) and portal vein (blood that needs _____) and direction as they pass through filtering liver cells and drains into _____ vein -> _____ vein -> ____ ____
Blood moves out of hexagon: Arrow of bile duct moves in the _____ direction bc hepatic cells are making bile and delivering it to the bile duct
Each corner of the hexagon
- Branch of Portal Vein, Hepatic Artery, Bile Duct
oxygenated, filtering, central -> hepatic -> vena cava
opposite direction
Gallbladder
As blood moves through the liver, away from the GI tract and toward the IVC, ____ moves in the opposite direction -> toward the (1) then into the (1)
Common bile duct merges with the _____ duct = (1) + (1) into duodenum
Bile -> common bile duct -> duodenum
pancreatic duct = bile + pancreatic juices
Overlapping Categories of Liver Function
(4)
Energy Metabolism and Substrate Interconversion
Protein Synthetic functions
Solubilization, transport, and storage functions
Protective and Clearance functions
Energy Metabolism and Substrate Interconversion
- (1) through gluconeogenesis and glycogenolysis
- (1) by pathways of glycogen synthesis, fatty acid synthesis, glycolysis, and the tricarboxylic acid cycle
- (1) from acetate, triglyceride synthesis from fatty acids, and secretion of both in VLDL particles
- (1) by endocytosis of HDL and LDL particles with excretion of cholesterol in bile, B-oxidation of fatty acids, and conversion of acetyl-CoA to ketones
- Deamination of amino acids and conversion of _____ to ____ via the urea cycle
- (1) and de novo synthesis of nonessential amino acids
- Glucose production
- Glucose consumption
- Cholesterol synthesis
- Cholesterol and trigyleride uptake
- Ammonia to Urea
- Transamination (ketone conversion used by brain for energy when glucose is unavailable)
Protein Synthetic Functions
Synthesis of various plasma _____, including a_____, ____ factors, b____ proteins, apo_____, angio_____, and insulin-like ____ factor I
proteins, albumin, clotting factors, binding proteins, apolipoproteins, angiotensinogen, growth
Solubilization, Transport, and Storage Functions
- D____ and p____ detoxification through phase I and II biotransformation reactions and excretion of _____
- Solubilization of ____ and fat soluble vitamines in bile for uptake by enterocytes
- _____ and secretion of VLDL and pre-HDL lipoprotein particles and ____ of HDL, LDL, and chylomicron remnants
- Synthesis and secretion of various binding _____, including transferrin, steroid hormone-binding globulin, thyroid hormone-binding globulin, ceruplasmin, and metallothionein
- Uptake and _____ of _____ A, D, B12, and folate
- Drug and Poison detoxification, Excretion of bile
- Fat
- Synthesis of VLDL, Clearance of HDL, LDL
- Proteins
- Vitamins
Protective and Clearance Functions
- Detoxificiation of _____ through the urea cycle
- Detoxification of _____ through microsomal oxidases and conjugation systems
- Synthesis and export of g______
- Clearance of damaged ____ and p_____, h_____, drugs, and activated ____ factors from portal circulation
- Clearance of b_____ and an_____ from the portal circulation
- ammonia
- drugs
- glutathione
- damaged cells, proteins, hormones, clotting
- bacteria, antigens
Overview of Liver Function (Notes)
Energy Metabolism = ____ production, ____ consumption, _____ storage, ch____ and t_____ synthesis (VLDL, HDL), major consumer of ____, oxidation of ___ ____, ____ conversion (used by brain for energy when glucose is unavailable)
Amino Acid and Protein Synthesis
- Critical Function: removes _____ coming from the __ _____
- Large amount of ammonia generated by GI tract predomoninantl by gut _____ consuming amino acids
- Liver converts ammonia into ____ -> some gets eliminated through ____ and some gets _____ to make (1)
- Important bc ammonia is highly _____
- Synthesizes large array of _____ critical for ____ function
- Produces our _____ proteins for ____ function
Glucose production, glucose consumption, glycogen storage, cholesterol and triglyceride synthesis, LDL, fatty acids, ketone
-
removes ammonia from the GI tract
- bacteria
- urea, urine, recycled to make amino acids
- neurotoxic
- proteins for bodily function
- complement proteins for immune function
Overview of Liver Function (Notes)
-
(1) = taking a molecule that is fat soluble and making it water soluble bc fat soluble substances are difficult to control the movement of
- Drug ______
- _____ conjugation: where sugar molecules are added to make it water soluble
- S_____
-
Protective and Clearance functions
- Glutathione: is a critical antioxidant that liver produces to help our bodies do what?
- Clears damaged ___, h____, dr____, b____, and antigens using _____ cells (liver macrophage)
-
Solubilization
- metabolism
- Bilirubin
- Storage
-
Protective and Clearance functions
- neutralizes reactive oxygen species
- cells, hormones, drugs, bacteria, Kuppfer cells
Liver Disorders
Clinical Manifestations of Liver Disease
(4)
Portal Hypertension
Ascites
Hepatic Encephalopathy
Jaundice
Portal Hypertension
=
- Caused by any disease that ____ or impedes blood flow through any component of the portal venous system or the vena cava
- Long term portal hypertension can lead to (or worsen (4)
Abnormally high BP in the portal circulation
- obstructs
- Varices
- Ascites
- Splenomegaly
- Hepatic Encephalopathy
Clinical Manifestations of Liver Disease (Notes)
Liver Failure = becomes _____, scar tissue and collagen
Critical Outcome is (1): probably the most important change that brings about the many other manifestations of lvier failure
- Portal Circulation: portal vein carries blood from GI tract to the liver -> as liver becomes fibrotic, blood flow is impeded and _____ in portal vein increases (usually a _-_ mmHg) -> pressure will ____ or ____ and once it reaches > __ mmHg you start to see pile up of complications
- Complications: varices, ascites, splenomegaly, hepatic encephalopathy as _____ levels rise
fibrotic
Portal Hypertension
- pressure increases (3-5mmHg) -> double, triple, _>_10 mmHg
- ammonia
Varices related to Portal Hypertension
Portal vein, its major tributaries, and the most important shunts (collateral veins) between the portal and caval systems
Normally portal vein is so large and pressure is so ____
As pressure rises, increase in blood flow to ______ circulation
- Superior and inferior mesenteric veins from GI tract leads to (3) places
Low
Collateral
- Portal Vein
- Splenic Vein -> engorges spleen/splenomegaly -> thrombocytopenia/anemia
- Coronary Vein -> engorges veins in the esophagus and stomach (varices) and can bypass liver entirely to drain into vena cava
Takeway: Portal Hypertension directly leads to many of these other manifestations
Varices
Distended and _____ Collateral veins - prolonged elevation in pressure in collateral veins causes their transformation into _____ are most common in (2)
Major clinical completion includes variceal _____
- May cause
- ______ of large volumes of blood
- Blood in ____
- A______
- Hemorrhagic ______
Tortuous, varices, ESOPHAGUS and STOMACH
Bleeding
- Vomiting
- Stool
- Anemia
- Shock
Varices (notes)
Varicose veins = _____, distended, tortuous veins, who often times valves in those veins have _____ -> risk of ____ formation bc you get a lot more blood flow through these veins than you normally see
- Usually ____ esophagus and ____
- Visualization through _____
- Dangerous and can ____ to cause massive hemorrhage
- Slow bleeding results in -> blood going ____ -> found in _____
- If it goes down GI tract, rise in _____ bc GI tract digests blood that has intestinal bacteria -> hepatic _____ which can lead to coma
Takeaway: whether its a slow bleed or alot of bleeding is a medical _____, mortality rate 50-60%
Enlarged, prolapsed valves, clot
- lower esophagus and stomach
- endoscopy
- rupture
- south, stool
- ammonia, encephalopathy
emergency
Ascites
The word ascites is of Greek origin (askos) and means ___ or ____
Ascites describes the condition of pathologic _____ accumulation within the abdominal _____
Ascites traps fluid in a “___ ____” from which it cannot escape
_____ is most common cause
bag or sac
fluid accumulation, abdominal cavity
“third space”
Cirrhosis
Ascites Contributing Factors
(think of ascites as a type of edema disorder):
- (1) increased BP in messenteric circulation
- (1) decreased plasma oncotic pressure
- (1) leads to expansion of plasma volume and increased blood pressure
- Portal Hypertension
- Hypoalbuminemia
- Impaired liver breakdown of ADH and Aldosterone
Ascites (Notes)
Third space =
- ____pleural space, _____ cavity, synovial sacs
- Difficult to get this fluid out compared to other ECP
Tend to see Ascites in 2 contexts
- (1) = can’t produce albumin bc function has decreased
- (1) = liver function but liver can’t produce enough protein bc you’re not consuming enough amino acids
Precipitating cause in fluid accumulation = (1)
Transcellular space surrounded by serous membranes
- interpleural space, abdominal cavity
- Liver Failure
- Starvation
Hypoalbuminemia
Ascites (Notes)
-
(1) increased pressure in veins coming from GI tract -> low albumin causes low plasma oncotic pressure so not enough _____ pressure to keep fluid in blood vessels so it leads out
- Also the HTN increases capillary BP that causes too much ____ force of fluid into peritoneal cavity
- Liver is critical in breakdown of hormones like (2) = as liver function declines, half life of these hormones increase -> excess ____ and ____ retention
-
A person with low _____ cannot keep fluid in their vascular space = fluid leaks out and manifests as ascites and peripheral edema -> __ low -> ______ think you don’t have enough plasma volume by increasing Na and water retention but all that fluid again just leaks out
- Tx = _____ but sometimes they’re too hypotensive
-
Portal Hypertension, pulling
- pushing
- ADH and Aldosterone, sodium and water retention
-
albumin, BP low -> kidneys
- Diuretics
Fluid Wave Test
Tests for what?
Ascites
Paracentesis
=
Precaution?
Physical removal of fluid from peritoneal cavity
Set of capillaries facing peritoneum creates pushing pressure of fluid out of blood vessels into peritoneum, and as fluid accumulates in peritoneum creates a counter pressure pushing the other way. Removing fluid disturbs that balance.
So you need to drain very slow w close hemodynamic monitoring bc if removed too quickly -> fluid shift from blood vessels out into peritoneum and BP will crash
Hepatic Encephalopathy
A complex neurological syndrome characterized by (3)
P______ changes, I______ impairment, and a depressed level of _______
May develop _____ or _____ with chronic liver disease
An important prerequisit for the syndrome is ______ of portal blood into the ______ circulation through ______ ______ vessels
Impaired cerebral function, Flapping Tremors, EEG changes
Personality, Intellectual, Consciousness
rapidly or slowly
diversion of portal blood into systemic circulation through portosystemic collateral vessels
Hepatic Encephalopathy (Notes)
Stems from Portal ______
Flapping tremors =
Root cause =
Primary problem =
Portal Hypertension
hand tremor
Bypassing of blood away from the liver
Elevation of circulating ammonia and the effects that ammonia has on the brain
Role of Ammonia
- Ammonia itself is very _______
- Ammonia changes the _______ of the _____ (w more exposure to ammonia, BBB becomes more permeable which allows ammonia greater access to the brain)
Changes in brain function in elevated ammonia levels
- Personality changes - more emotionally _____, ag_____, _____ impairment
- More _____ levels of consciousness as ammonia gets higher
- Neurotoxic
- Permeability of the BBB
- emotionally labile, agitated, intellectual impairment
- Depressed lvls of consciousness
Role of GABA
- ___ tract also releases alot of GABA (neurotransmitter) - so there is a fair amount of GABA that enters the liver in the portal circulation
- GABA normally enters portal circulation and gets _____ by liver
- So when blood is bypassing liver, more GABA enters _____ circulation, enters ____ and causes _____ brain function
- GABA vs. Ammonia?
- GI tract
- metabolized
- general, brain, depressed
- GABA does play a role but Ammonia is the primary neurotoxin - will see improvement when removing ammonia
Grading of Symptoms of Hepatic Encephalopathy
Grades 0-4?
- Clinically normal mental status but minimal changes in memory, concentration, intellectual function, and coordination
- Coma with or without response to painful stimuli
- Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time
- Mild confusion, euphoria, or depression; decreased attention; slowing of ability to perform mental tasks; irritability; and disordered sleep pattern, such as inverted sleep cycle
- Somnolent but can be aroused, unable to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech
Treatment (2)
- Grade 0
- Grade 4
- Grade 2
- Grade 1
- Grade 3
Low protein diet, Lactulose to keep from getting constipated and elevated ammonia
Grade 1 may describe the baseline of a person with late stage liver disease -> then if something happens to elevate their ammonia - protein rich meal and constipation will acutely elevate ammonia into grade 2 -> acute encephalic events require hospitalization
Jaundice
Results from any type of liver _____ that elevates circulating _______, reflects hepatocellular injury and death
- Bilirubin has a ____/____ color and highly ___ soluble, so as blood levels rise it deposits in the _____
- Manifestion =
- In darker skin individuals, easier to detect where?
injury, bilirubin (hyperbilirubinemia)
- yellow/orange, fat soluble, deposits in skin
- yellow/orange color of skin and sclera
- Easier to detect in eyes and soles of hands and feet
Bilirubin Production
Bilirubin comes from the ____ group that represents the oxygen binding site of hemoglobin
- _____ is part of our immune system and is also where old rbcs get trapped and processed: aging rbcs get dismantled
- Protein and Iron in the RBCs are ______
- Hemoglobin is _____
- ______ gets converted to _______
Heme Group
- Spleen
- recycled
- broken down
- Heme group gets converted to bilirubin
Bilirubin Processing
- Bilirubin leaves spleen through the splenic _____ and travels to the _____ -> at this point it is ______ (naked) bilirubin that is highly ______ soluble
- Lipid soluble things travel in the bloodstream bound to _____ -> travels through portal vein to liver where Hepatocytes _____ bilirubin by adding a _____
- Conjugated bilirubin is _____ soluble and liver adds it to ____ (what gives bile its color) -> leaves liver through bile duct and enters duodenum during digestion
- Splenic vein -> liver, unconjugated, fat soluble
-
Albumin, Hepatocytes conjugate bilirubin by adding a sugar
- Water soluble, Bile
Bilirubin Removal
In gut, bilirubin can get unconjugated by ______ and gets _____ or/most of bilirubin is converted to ________ (SBG) by gut bacteria and is what makes feces _____
bacteria, reabsorbed, Stercobilinogen, brown
Bilirubin Production, Processing, and Removal Summary
=
Results in (2)
Naked bilirubin from heme group comes from spleen -> very fat soluble and travels through portal vein attached to albumin to liver -> liver conjugates it by adding a sugar and makes it water soluble, adds it to bile duct -> enters duodenum during digestion
1) gets unconjugated and reabsorbed
2) rest is turned into SBG that makes your poop brown
What happens in Liver Failure
That leads to circulating bilirubin and jaundice?
(3)
- In acute liver injury, injured cells are going to stop conjugating bilirubin -> fat soluble naked bilirubin levels rise and cause jaundice
- Don’t have to be in liver failure to be jaundiced, ie Hep A (acute injury, can recover)
- Portal Hypertension as a result of liver disease -> less bilirubin getting to liver bc its bypassing it
- Hypoalbuminemia -> less albumin to carry naked bilirubin into liver so quickly diffuses out of bloodstream and into tissue
Summary of Liver Failure Manifestations
Effects of Portal Hypertension
- Esophageal _____ -> if rupture ->
- (1) or
- (1): black tarry stool, smells awful, resulting in bleeding in upper GI tract that gets passed down and digested through the body
- ____megaly
- ____ abdominal veins
- A______
- _____ varices (hemorrhoids)
- Esophageal Varices
- Hematemesis
- Melena
- Splenomegaly
- Dilated Abdominal veins
- Ascites
- Rectal varices
Summary of Liver Failure Manifestations
Effects of Liver cell failure
- ____ from hepatic encephalopathy
- ____ Hepaticus (breath smells like freshly opened corpse)
- _____ veins (little hemorrhages) on periphery ( a result of coagulopathies from not enough clotting factors in liver failure)
- ______ from impaired hormone elimination
- _____ hand tremor
- Ankle ____ + generalized peripheral edema
- Coma
- Fetor Hepaticus
- Spider veins
- Gynecomastia
- Flapping
- edema
Hepatorenal Syndrome
=
Form of kidney injury where the hemodynamic changes in liver failure reduces blood flow to kidneys and stimulates them to constantly retain fluid -> kidney failure going along with liver failure is a common combination and cause of death
Acute Peritonitis
=
- Can precipitate (1) by bacteria produce tons of ammonia
- Tx =
Where bacteria in GI tract increase in # and cause infection of peritoneal cavity (dt loss of immune function that liver serves) -> less trapping of bacteria by liver, bacteria finds its way to circulation, GI tract bacteria also increase in # -> a bacterial bloom
- hepatic encephalopathy
- Antibiotics
Hepatitis
(cause of liver injury)
=
(5)
Inflammation of Liver
Hepatitis Viruses that Preferentially infect hepatocytes and cause liver inflammation and cell death
Hep A
Hep B
Hep C
Hep D
Hep E
Hepatitis A and E
Transmission =
Effects =
Fecal oral route, virus is shed through feces -> consuming food that’s been contaminated by someone with poor handwashing skills
Acute illness with Full recovery (2 wks post exposure and emergence of S/S, then a few weeks after jaundice, can recover fully w/o tx)
Hepatitis B
Transmission =
Effects =
____ series available
Risk of contracting _____
Blood, Bodily fluids (vaginal secretions, semen)
For minority of pts will cause acute illness ten full recovery, but majority pts will cause chronic infection (but only a small percentage of those with chronic infection will develop liver cirrosis)
Vaccine
Hep D
Hepatitis D
Transmission =
Effects =
Blood, Bodily fluids
Requires presence of Hep B to be infected by it (so is actually a complication of being infected with Hep B) - when you do get D on top of B -> Fulminant liver failure (acute liver failure)
Hepatitis C
Transmission =
Effects =
Blood and bodily fluids
Chronic, devastating infection that destroys liver and cirrhosis
Normal Biopsy vs. Hepatits
- Normal Biopsy = Hepatic ____ present (bile duct, hepatic artery, portal vein), cells _____ in size and color, a ___ of connective tissue around triads
- Mild Hepatitis = around triads a bit ____ fibrotic tissue showing signs of chronic _______ and acutely _____ hepatocytes that are enlarged and discolored
- Moderate Hepatitis: scar tissue/connective tissue now ____ together, more acutely inflamed _____ (blood enters through hepatic artery and portal so as scar tissue worsens) -> ______ of blood flow through liver -> ____ _______
- triad, uniform, bit
- more fibrotic tissue, chronic inflammation, acutely inflamed
- banding, hepatocytes, impedence, portal hypertension
Alcoholic Hepatitis
Chronic exposure to _____, liver breaks it down and produces byproduct of _____ _____ which is highly _____
(1): initial, early stage where acetyl aldehyde blocks _____ of (1) so fat accumulates in liver cells (is ______)
Elevate liver enzymes, biopsy shows _____ color to hepatocytes that are inflamed and enlarged
ethanol, acetyl aldehyde, hepatoxic
Fatty liver disease, blocks oxidation of fatty acids, reversible
yellow
What are the 2 leading causes of Liver Cirrhosis?
Hep C
Alcoholism
Viral Hepatitis
Clinical Manifestations
Acute viral hepatitis causes abnormal liver function ____ results
The serum aminotransferase values (2) are elevated - how?
liver function test results
Aspartate Transaminase (AST), Alanine Transaminase (ALT) - when liver cells die they release these enzymes into bloodstream so the more we see, reflects liver cell death
3 Phases in the Clinical Course of Viral Hepatitis
-
_____ Phase
- Begins about __ weeks after exposure and ends with appearance of _____. Symptoms may include? Also common is _ _ _ pain and weight ____. The virus is highly ______ at this stage.
-
______ Phase
- Begins about _-_ weeks after prodromal phase and lasts anywhere from _-_ weeks. Is the _____ phase of illness. Hepato_____ damage and Intrahepatic bile _____ causes jaundice.
- ______ or ______ Phase
-
Prodromal
- 2 wks post exposure, ends with appearance of jaundice. Fatigue, anorexia, malaise, n/v, headache, hyperalgia, cough, low grade fever; RUQ abd pain, weight loss, highly transmissable
-
Icteric (Jaundice)
- 1-2 wks, 2-6 wks, acute, Hepatocellular, bile stasis (first appearance of jaundice, peak severity of this acute illness)
- Recovery or Chronic
Liver Cirrhosis
= Liver ____ through ______
Very n_____, _____ in size, feels _____, biopsy shows large _____ of fibrotic tissue separated by nodules of _______ liver, so liver is still trying to regnerate but really isn’t working bc so much fibrosis, and areas of n______
Occasionally, evidence of hepatic ______ (chronic inflammation increases likelihood)
Liver failure through fibrosis
nodular, shrunken, hard, bands of fibrotic tissue, regenerated liver, areas of necrosis
Hepatic Carcinoma
What is picture A and B?
Cirrhotic liver with micronodules
Cirrhotic liver with macronodules, could also have carcinoma (dark spots)
Cirrhosis
An _______ inflammatory disease that disrupts st____ and f_____. Is characterized by chronic ______ that leads to ____ of fibrosis in between _____ of _____ liver tissue.
Examples
- ______ cirrhosis (includes a reversible fatty liver phase)
- ______ cirrhosis (post ____ hepatitis B, C, D)
Cirrhosis develops slowly over a period of several ______
The severity and rate of progression depends on the _____
irreversible, structure and function, inflammation, bands of fibrosis in between nodules of regenerated liver tissue
- Alcoholic
- Postnecrotic (viral)
years (about 5-10 years with cirrhosis to lead to death so can still live for a while)
cause
Fulminant Hepatitis
=
Causes (3)
Acute liver failure thats very rare and has very few causes
- Hep D after B
- Environmental exposure to highly hepatotoxic agents (ie solvents in dry cleaning)
- Tylenol overdose (when acetaminophen is broken down produces products that damage livr and slow down acetaminophen metabolism -> vicious cycle)
