Liver Flashcards
1
Q
Facts about liver?
A
- big filter (think of it like a swamp
- liver- large, lipophilic moelecules–> slowly filters
- kidney- small, water soluble molecules
- biggest organ in the body
- blood supply
- portal system- blood supply from all organs (lower esophagus to rectum)–> portal system–> liver
- everything except kidney and gonads
- eat something poisonous- liver detoxifies it and clears it with enzymes
- portal system- blood supply from all organs (lower esophagus to rectum)–> portal system–> liver
2
Q
What is the hepatic portal circulation?
A
- Hepatic portal circulation. In this unusual circulatory route, a vein is located between two capillary beds. The hepatic portal vein collects blood from capillaries in visceral structures located in the abdomen and empties into the liver. Hepatic veins return blood to the inferior vena cava.
- Blood supply from all organs (lower esophagus to rectum) → go to portal system → drains to liver
- (except kidneys and gonads)
- Eat something poisonous- liver detoxifies it and clears it
- Blood supply from all organs (lower esophagus to rectum) → go to portal system → drains to liver
3
Q
Which organs are/are not involved in protal system?
General function of organs?
A
- All blood from abdominal viscera (from lower esophagus to rectum) drains through hepatic portal circulation to liver
- if you eat any toxins, the liver has first pass at them, before systemic exposure
- Spleen and the pancreas also drain to the liver
- Kidneys do NOT drain to liver
- Right and left and common bile ducts drain bile from liver
- (Liver) Right/left hepatic duct→ Common hepatic duct meets with cystic duct (from gallbladder) → forms into common bile duct → meets with pancreatic duct → duodenum
- Gallbladder- green (bile)
- Bile- made of molecules used to emulsify fat, amphipathic (both water and lipid cholesterol) and filtered toxins we try to get rid of
- Liver constitutively makes bile which is stored in the gallbladder
- BUT bile is only released into duodenum when we eat
- Pancreas: produces digestive enzymes that are released into duodenum after eating
- Sphincter of Oddi controls release (when it opens, everything is allowed passage
4
Q
What is the liver lobule?
A
- fundamental unit of the liver= lobule
- corner of hexagon are portal triads
- in between are sinusoidal capillaries which are lined by hepatocytes (parenchymal cells of liver)
- oxygenated and deoxygenated blood mixes here
- very convuluted, blood moves very slowly to allow time to clear toxins
-
kupfer cells- macrophages in liver
- looking for anything in blood that we need to get rid of
- Ito cells- fat storing cells
- Bile duct
- Bile canaliculi
5
Q
What composes the portal triad?
A
- Hepatic portal vein (80%)- brings in blood from portal system (lower esophagsu–> rectum, all except kidney/gonads)
- deoxygenated blood from capillary bed
- vein lumen is much bigger
- most of blood coming to liver is portal blood
- Hepatic artery (20%)- brings in fresh blood
-
carries oxygenated blood
- smaller lumen, thicker wall, less blood
-
carries oxygenated blood
- Bile duct
- big, larg lumen, thin wall, low pressure
- Lymphatic vessel
- huge. half of lymph produced by your body everyday is produced by your liver
- lymph should be relatively protein free (because it’s all ISF and the protein should stay in capillaries)
-
half lymph is protein free, half has same concentration as blood
- therefore protein concentration lymph is about half that of your blood
-
“bimodal concentration”
- half lymph is coming from liver
overall, liver has relatively low oxygen supple becaues most blood coming in is deoxygeanted
6
Q
What are 3 functions of hepatocytes?
A
glucose/protein
bile
bilirubin
7
Q
How does liver maintain blood glucose?
A
- Liver take glucose and stores it as glycogen after meals (reduces post meal hyperglycemia)
- if haven’t eating in a few hours, liver breaks down glycogen and releases glucose
- if person has liver fialure, then individual will become hypoglycemic between meals
- also see much higher glucose concentrations immediately after a meal
8
Q
What role does liver play in protein formation?
A
- After meal, take up amino acids, deliver to hepatocytes for synthesis of plasma proteins (liver makes almost all proteins except for antibodies which are made by plasma cells)
- liver also makes lipoprotines (LDL and VLDL)
- some amino acid is stored in hepatocytes
- reserve of amino acids in liver (liver can store up to a days worth)
9
Q
What is the enterohepatic circulation of bile salts?
A
- Liver makes bile (bile salts= bile acids)
- bile acids= H attached
- bile salts= Na attached
- become bile anion as soon as it’s in solution
- Bile salts are amphipathic and used to emulsify fats, and are negatively charged
- liver starts with cholesterol, sticks something polar on one end and releases it to be bile
- released into bile canaliculi: gap between two cells–> bile duct–> hepatic duct–> gallbladder–> duodenum
- CCK makes gallbladder squeeze when eating–>releases bile–> emulsifies fat
- in duodenum, it helps digest fat, working as an emulsifier
- in ileum, we reabsorb bile, blood from ileum goes to liver and we reabsorb the bile, reprocess and recycle it (90% of bile is recycled)– (where some cholesterol lowering meds work)
- 10% new bile
- 10 cycles before we lose it
- if not reabsorbed, liver needs to make a lot more bile (cholesterol in body being used for bile and therefore lowers levels)
10
Q
What is bilirubin metabolism like?
A
- Bilirubin is the result of broken-down heme coming from RBCs as well as from any protein that contains heme
- Hemoglobin= globular protein plus heme (when recycling, globular protein is brokwn down and we recycle the amino acids)
- Heme= iron + porphyrin ring
- Recycle everything we can
- iron- recycle into iron pool
- porphyrin (throw away)–> biliverdin (green)–> unconjugated billirubin (yellow/orange)
- unconjugated bilirubin is lipohilic (lipid soluble) and therefore can’t get rid of it in the kidney, so it needs to go to liver (catches ride on albumin)
- unconjugated bilirubin and glucuronic acid ( makes bilirubin is water soluble with enzyme glucoranyl transferase)–> conjugated (water soluble) bilirubin, excreted with bile into canaliculi
- conjugation= adding water soluble molecule to a lipid soluble molecule
- Bilirubin is component that gives feces dark color (urobilinogen)
- some gets reabsorbe in colon–> kidney can now get rid of it becaues it is water soluble (can make urine dark)
From slide later on in ppt:
- Normal bilirubin production (0.2 to 0.3 g/day) is derived primarily from the breakdown of senescent circulating erythrocytes, with a minor contribution from degradation of tissue heme-containing proteins.
- Extrahepatic bilirubin is bound to serum albumin and delivered to the liver.
- Hepatocellular uptake and
- glucuronidation by glucuronosyltransferase in the hepatocytes generates bilirubin monoglucuronides and diglucuronides, which are water soluble and readily excreted into bile.
- Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogens. The urobilinogens and the residue of intact pigments are excreted in the feces, with some reabsorption and re-excretion into bile. The urobinogen that remains in the colon is converted to stercobilin. Stercobilin is resposnbile for brown color of feces
11
Q
How does fibrosis of the liver occur?
A
- Fibrous tissue is formed in response to inflammation. With time, fibrous strands link regions of the liver, a process called bridging fibrosis
- With continuing fibrosis and parenchymal injury, the liver is subdivided into nodules of regenerating hepatocytes surrounded by scar tissue
- Fibrosis is considered an irreversible consequence of hepatic damage and has lasting consequences on patterns of blood flow and perfusion of hepatocytes.
-
Fibrosis: inflammation→ macrophages activate, stimulating fibroblasts to lay down collagen → scar tissue
- lots of collagen in liver (blue stain): get fibrous bands around pieces of liver forming nodules; impairs blood flow and function of liver (normally no collagen in liver- remodels thicker and thicker→ cirrhosis)
- Insult to liver → neutrophils come out and clean up → macrophages → fibroblasts→ lay down collagen
12
Q
What are stellate cells?
A
- Normally sit in liver and are quiescent (store Vit A)
- If they get activated (by kupfer cells aka macrophages)–> become fibroblast
- Activated Ito/Stellate cells–> become fibroblasts–> lay down collagen (scar tissue)
13
Q
Which enzymes show hepatocyte integrity?
A
Serum aspartate aminotransferase (AST, SGOT)
Serum alanine aminotransferase (ALT, SGPT)
- normally found in hpeatocytes, if you find them in the blood= hepatocytes are dying
- if one goes up more than the other, suggests alcoholic vs viral
14
Q
Which enzymes show biliary tract integrity
A
- Serum alkaline phosphatase (AP, ALP, ALKP, etc)
- Also found in bones
- Serum gamma- glutamyltransferase (GGT)
if increase, cell of biliary tract are dying
15
Q
How is serum bilirubin classified?
A
- Direct (conjugated)
- Total (conjugated + unconjugated)
16
Q
What tests show mepatocyte function?
A
- Serum albumin
- binding protein of choice
- if total protein is low, and albumin is low= liver dysfunction
- if total protein normal and albumin low= liver is ok, someone else is making too much protein
- INR (Prothrombin time)
- liver failure= less coag factors, increase INR
- Liver makes clotting factors and plasminogen (stops clotting)
- coagulopathy- clot slower when need it and clot faster when you don’t need it
- serum ammonia
- two ureas- can cross BBB and cause encephalopathy
-
when liver does gluconeogensis, makes ammonia
- normal: amino acid–> take 2 AA nad CO2 and stick together–> urea (ammonia –> urea in liver)
- if you can’t do that, ammonia increases in blood
- if elevated- liver not converting ammonia to urea
17
Q
What is MELD?
A
Model for End-Stage Liver DIsease
- 3.8 * bilirubin + 11.2 * ln (INR) + 9.6 * ln (Cr) +6.43
- dont’ need equation
- as liver fails, the kidneys stop working and creatinine goes up
- this gives you measure about how bad your liver is (higher MELD, higher mortality and need for liver tx)
- the worse off someone is, the better benefit a liver transplant was
- lower MELD score would do worse post transplant
- Factors considered= bilirubin, INR, creatinine
- around 50, have one month to live
18
Q
What are some consequences of liver disease?
A
- Jaundice: turning yellow from bilirubin
- Cholestasis
- Hypoalbuminemia: low albumin in blood → not making albumin
- Hyperammonemia: high ammonia → liver not converting ammonia to urea
- Hypoglycemia: between meals liver controls glucose liver, if liver is failing glucose starts to fall (hypoglycemia between meals)
-
Fetor hepaticus: if some toxins/waste products not removed by liver, find another way out; one of those ways is lungs
- (“breath of death”) waste products are volatile- low boiling temp (exhale them)
-
Hypogonadism: normally liver gets rid of steroid hormones
- Estrogen is problem without proper liver clearance (build up) –> hypothalamus signals negative feedback–> decreased LH & FSH→ decrease size of genitals!
- Steroids- lipid soluble- liver can’t clear them if failing
-
Gynecomastia: not clearing steroid hormones (Androgens→ (Aromatase) → estrogen/estradiol) → causing female characteristic of breasts
- obese, alcoholic males getting breast cancer, fat converts testosterone to estrogen, a failing liver is not clearing estrogen –> breast development
- Palmar erythemia: red palms, inappropriate capillary sphincter relaxation (blamed on estrogen)
- Spider angiomas (telangiectasia): red dilated capillaries – failure of capillary sphincter – (blamed on estrogen)
-
Depression (added to list)
- ppl with liver failure have psychological problems (hepatic encephalopathy)
- Weight loss
- Muscle Wasting
19
Q
What are consequences of hepatic portal hypertension?
A
- Hepatic Portal Hypertension
- All blood from the abdominal organs is draining through the liver
- If blood can’t get through liver, blood is going to back up – causing portal hypertension
- Ascites: fluid accumulation in abdomen/edema
- blood trying to escape through other routes (3 other ways out)
- Continental Divide: (3)
- 1. esophageal varices (lower esophagus)
- 2. hemorrhoids (rectum)
-
3. caput medusae (umbilicus)
- Connections to umbilicus to liver and IVC
- Splenomegaly: enlarged spleen (only place that gets enlarged)
20
Q
Life threatening complications for liver diseae?
A
- Multiple organ failure
- Coagulopathy: Have a problem with clotting factors (slow to clot, slow to unclot- bc plasminogen made by liver too)
-
Hepatic encephalopathy:
- Build-up of ammonia and other toxins (lipophilic products) can cross blood brain barrier –> encephalopathy
- ammonia gets blame but usually combo of different toxins
- Build-up of ammonia and other toxins (lipophilic products) can cross blood brain barrier –> encephalopathy
-
Hepatorenal syndrome: if liver stops working, few days later kidneys stop working (nothing wrong with them, still has blood flow)
- if fix liver, kidneys come right back (possibly d/t splanchnic circulation) → MELD score…
- `nothing wrong with kidney but seems to have decrease in renal blood flow
- if fix liver, kidneys come right back (possibly d/t splanchnic circulation) → MELD score…
-
**Esophageal varices rupture- most common cause of death
- Vomit and bleed to death
- Vomiting is harsh on esophagus→ stretch and tears (wet/slimy not good for clotting environment)
- Tx: tube down throat and inflate it (pressure to stop bleeding)
- 30% will die, 70% will do it again and then another 30% chance of dying
- Tx: tube down throat and inflate it (pressure to stop bleeding)
- Hepatocellular carcinoma
24
Q
What is cholestasis?
A
- Blockage of biliary duct, Unable to move bile out of hepatocytes and into bile duct
- If passage gets clogged, bile gets blocked→ damage to hepatocytes bc of build up in canaliculi→ cells accumulate inclusions (brown spots on picture- things that shouldn’t be inside a cell) → hepatocytes cells die as they accumulate inclusions(apoptosis)(3)
- think of it like a clogged septic line
Schematic illustration of the morphologic features of cholestasis and comparison with normal liver. In the parenchyma (top), cholestatic hepatocytes (1) are enlarged with dilated canalicular spaces (2). Apoptotic cells (3) may be seen, and Kupffer cells (4) frequently contain regurgitated bile pigments. In the portal tracts of obstructed livers (bottom), there is also bile ductular proliferation (5), edema, bile pigment retention (6), and eventually neutrophilic inflammation (not shown). Hepatocytes immediately adjacent to portal tracts (7) are swollen and undergoing toxic degeneration
37
Q
What is fatty liver?
A
- Fat inside hepatocytes (main cause is alcohol-damaged liver)
- Yellow blob
- Make cholesterol (particle or molecule)
- LDL- large molecule with lipid layer and proteins, middle triglycerides and cholesterol
- Liver makes this → dumps in blood → cells pull in and use
- Too much ETOH → liver takes up → converts to fat (but liver impaired and cant make proteins to convert to LDL) → triglycerides building inside cells
- White stuff- fat inside hepatocytes
- Liver will be enlarged
- Liver can take up the alcohol but CAN’T get rid of the fat, and it builds up in liver (reversible: stop drinking and everything goes back to normal)
- however, this is an inflammatory process, and therefore you get collagen laid down… if persists, can develop cirrhosis
Nonalcoholic fatty liver disease: obese people → get bariatric sx and goes away
Alcoholic liver disease: macrovesicular steatosis, involving most regions of the hepatic lobule. The intracytoplasmic fat is seen as clear vacuoles. Some early fibrosis (stained blue) is present. (Masson trichrome.)
38
Q
What is alcoholic liver disease?
A
- Hepatic steatosis (fatty liver) = 90-100% (% alcoholics will end up with..)
* Steatosis- drinking too much (fatty liver)- Don’t drink → normal liver (clears fat)
- Normal AST/ALT bc cells not dying in fatty liver
- Keep drinking (thicker collagen strands)→ cirrhosis
- Don’t drink → normal liver (clears fat)
- Hepatic steatosis (fatty liver) = 90-100% (% alcoholics will end up with..)
- Alcoholic hepatitis = 10-35%
* Hepatitis- real inflammation- Will have elevated AST/ALT + unconjugated bilirubin
- Severe ETOH intake results in killing hepatocytes
- **More you damage liver- fewer cells left to detoxify ETOH (every hepatocyte works twice as hard) then end up cirrhosis with continued exposure
- Alcoholic hepatitis = 10-35%
- Cirrhosis = 8-20%
* Alcoholic cirrhosis. Nodules of varying sizes are entrapped in blue-staining fibrous tissue. (Masson trichrome.)- Blood not flow through nodules
- Should be low resistance but now BF high pressure (portal HTN/ascites)
- Cirrhosis = 8-20%
