GB, liver, pancreas Flashcards
- Cholelithiasis
Types: cholesterol and pigmented (ca bilirubin salts)
Patho of cholesterol stones:
1. Things which alter bile composition (cholesterol saturation
estrogen, prostagladin/mucin production,
increased water/lyte absorption)
2. Decreased GB motility (sympathetic stimulation, estrogen, decreased Oddi sphincter relaxation
Patho of pigmented stones:
things that increase bilirubin levels (biliary tract infection, unconjugated bili, intravasc hemolysis)
- Cholecystits Acute
Inflamation of GB neck, bile duct, cystic duct caused by obsturction. Leads to ischemia, mucosal epi injury due to stone or bile, infection
Clinic manif: RUQ pain ^alk pase hyperbilirubinemia, N/V, anorexia fever Murphys sign
- Chronic cholecystitis
Ongoing inflamm
possible calcificaton to wall.
clinical manif:
RUQ pain
N/V
inolterance to fatty foods
- Liver - Structure
Receives 25% of cardiac output.
1. Blood supply (sinusoids have combines art and ven systems)
Venous - portal vein
Art - hepatic artery
Central art and hepatic vein drain into inf vena cava.
2. Organization lobulues acinus parenchymas between vessels (zone 1 proximal to blood supply - zone 3 distal to blood supply et shows necrosis first) 3. Cells - a. Hepatocytes between sinusoids and bile canaliculus. b. Kupffer cells (macrophages) c. Stellate cells or lipocytes (sotre fat) 4. Space of Disse spaces between hepatocytes and endo cells lymphatic channels 5. Bile duct and canaliculi
- Liver - Physiology - Energy metabolism
- Carb metabolism - stores glucose, glucogenolysis, gluconeogeneis, carbs into triglycerides.
- Protein metabolism - degrade amino acids used for energy, glucose/protein synthesis, urea breakdown
- Lipid metabolism -
Fatty acids degrade into Acetyl Co-A, et ACA synthesizes cholesterol.
- Liver - Physio - Plasma protein synthesis
Albumin, globulins, hormones, clotting factors
- Liver - Physio - Solubilizes, transport, storage
- Bile (contain acids, bili, choles)
- bile acids (produced by hepatocytes) - reabsorbed in intestines (distal ileum) to be recycled.
Solubilizes & emulsifies lipids.
Transports fatty acids. - Bilirubin - hepatycytes solubilize bili > conj bili et exreted into caniculi.
- Drug metablism - converts to more soluble forms (in ER of hepato and mitochondria)
Phase 1 - CYP450 oxidzes, reduces, hydrolysis drugs.
Phase 2 - conjugates intermediate products et solubilizes metabolites.
Glutathione produced to decrease oxidative stress. - Stores vitamins, metabolizes steroids, blood reservoir
- Liver - Physio - Protective and clearance functions
- Kupffer cells - remove bacteria/antigens from circulation
- Hepatocytes remove damaged plasma proteins
- Ammonia metabolized to urea
- Glutathione- hepatic IC antioxidant
- Hyperbilirubinemia - unconjugated (indirect)
Increased breakdown of RBCs
Reduced or impaired hepatic uptake of unconj bili
Clinic Manif:
increased bili and unconj bili levels (total bili)
Unconj bili may diffuse to brain
Normal colored stools.
- Hyperbilirubinemia - conjugated
Decreased hepatocyte excretion of bili into bile caniculi due to damage, deficiency, or dysfunction of membrane.
Impaired intra or extrahepatic bile flow
Clinic manif: jaundice elevate conj/unconj bili level ^ alk phase bili in urine clay colored stools
- Cholestasis - failure to excrete bile
Due to hepatocellular dysfunction (not able to manuf bile) Intrahep obstruction (decrease bile flow, caniculi obs) Extrahep obstruction (bile duct obs)
- Portal hypertension- increased resistance to portal blood flow
Prehepatic - obstructive thrombosis or narrowing of portal vein or splenomegaly
Intrahepatic - obs of blood flow within liver such as cirrhosis
Posthepatic - obs of flow through hepatic veins such as severe right sided heart failure, pericarditis, hep ven thrombosis
- Hepatic injury - Inflammation
- Hepatocyte swelling . accumulates IC substances,
loss of cytoplasm,
necrosis,
apoptosis
Kupffer cells (macrophages) hypertrophy, beocme APC, incite cytokine release
Stellate (lipid) cells proliferabe and beocme fibroblasts >secrete fibrin andcollagen which can contract.CAn revert.
Obstruction of bile canaliculi due to swelling
- Hepatic Injury - Regeneration
Cell injury or death stimulate replication.
If unable, progenitor cells located in intrahepatic ductules.
- Hepatic Injury - Clinical manif
- anorexia, n/v, wt loss, hepatomegaly, ruq pain, jaundice, fever, elevated enzymes
- altered liver func (carb metabolism, fat lipid metablism, ^lipidemia, bili conjugation, bile production/excretion/ drug detox, decreased vit b storage, protein met, decreased proc of plasma protein (hypoalb, clotting factor), ammonia detox)
- Acute hepatitis - Drug induced liver disease (toxic)
- Specific drugs (tylenol)
- Mech
toxic to hepatocytes zone 1
intermediate toxicity zone 2-3
immune - act as hapten> autoimmune response
Patho: hepathocyte injury
Clinic manif may be delayed or immediate from hep injury, chronic hep to acute liver failure
- Acute Hepatitis - alcoholic liver disease (toxic)
Patho:
Breakdown produces acetaldehyde>acetic acid.
- injure cell membranes’
- react with proteins and inactivates enzymes
- Ethanol impairs protein synthesis and mitochondrial func (Inhibits glucose prod, fat oxidation,lipoprotein trasnport > fatty liver.
2. Requires oxygen increasing O2 uptake, cauisng hypoxia of sinusoidal blood to service zone 3 cells.
3. Hep injury and hypoxia> inflamm response (hepatocyte swelling, Kupffer>cytokines, endothelin release, Mallory’s bodies tangles)
4. Fibrosis
5. Hepatomegaly
6. Can regenerate if not fibrosed.
7. Continued injury > liver disease and cirrhosis.
- Hepatitis A
Single strand RNA virus (fecal oral) which replicates in liver.
Tcell mediated damages infected hepatocyts.
- Hepatitis B
Double stranded DNA virus (parenteral).
Infected cells killed by immune system (viral antigen on hep cell surface)
If unable to clear virus > chronic hepatitis.
- Hepatitis C
Single stranded RNA virus (parenteral). 80% risk for chronic hepatitis due to strong CD4/8 response. Ongoing hepcell damage contines.
- Hepatitis
Patho; hepatic injury
Clinic manif (3 stages)
1. Prodromal -onset of symptoms with appearance of jaundice, extrahep s/s (HA, photophocia, cough, myalgisas, rash), viral antigen measured.
2. Icteric - symptoms improve, ^liver enzymes, light stool, ecchymosis, jaundice, encephalopathy
3. convalescent - resolving symptoms, abn LFTs
- Chronic Hepatitis
Necrosis or inflamm > 6mos. Etio: persistent hep virus drugs/alcohol genetic disease metabolic syndrome immune related
Patho;
Ongoing inflamm & inflitration of lymphocytes
Hep cell necrosis/apoptosis
Fibrosis
Kupffer (macrophage) > cytokine release > damage to hepcells
Stellate cells - secrete collagen/fibrin and multiply > high density matrix in Space of Disse.
Edema> loss of endo fenestrations and microvilli (loss of filtration systems)
More depositon of fibrin/collagen in space of disse > bile duct damage
- Cirrhosis
Irregular, regenerating nodules with fibrous bands between nodules.
Etio: Viral hepatitis chronic biliary obs drugs, alcohol immune genetic infiltrative/metabolic d/o heart failure (ischemia)
- Cirrhosis
Patho: continued process
ischemia, diffuse fibrosis, nodules, decreased blood/bile flow
STellate cell increase >upregulate collagen/fibrin deposition >tight matrix
Hepcytes surrounded by fibrotic bands >
Parenchymal nodules
Clinic manif: constitutional symptoms portal htn ascites hypoalb peripheral edema altered glucose metabolism bacterial peritonitis varices and bleeding decrease hormonal metabolism hepatocellular carcinoma hep encephalpathy hepatorenal syndrome (renal failure)
- Ascites
Resistance to portal flow (blood and lymph)
These back up into the peritoneal cavity.
Hep lymph has ^oncotic pressure pulling fluids into peritoneal cavity.
2.Increased Na and water retention due to :
^sinusoidal pressure > underfilling of central vein > decreasing volume and renal perf.
This ^ renin secretion > renal Na.water absorption >vasoconstriction
- Hepatic encephalopathy
Caused by ammonia > brain edema
impaired BBB
^ GABA levels since not removed by hepcells
Altered AA metablolism>false neurotransmitters
