digestive disorderas Flashcards
Normal Liver-stroma
Reticular fibers
- chomphor cell
- eto cell
- endoth. cell
Normal Liver-parenchyma
Hepatocytes -lrg cells w/ lots of organelles -stem cells like=Divide/regen. during lost hepatocyte -Function :detox :bile production :blood prot. :glycogen storage
Normal liver-received blood from which organ
Directly from GIT
-perfusion determine susceptibility to toxin
Normal liver-vasculature and system
Supportive via proper hepatic artery
Incre. O2 level
Normal Liver-Vasculature function
Digestive tract
Via Portal Vn=incre. Nutrients
Normal liver-blood flow
Blood–>sinusoid-parenchyma(b/w hepatoxyte) –>central vn(sublobular vn–>hepatic vn–>exit liver)
Normal liver-portal triad
Liver receives BF from 3 BV -bile duct=bile produce b/w hepatocyte and flow periphers (away central vn) -hepatic art=incre. O2 :goes to central vn. -Portal vn=incre. nutrients :goes to central vn :from GIT :kaupffer cells=liver res. MAC (w/ endoth. cells)
Normal liver-liver perfusion
Classic hepatic lobule
-drain blood from portal vn/hep. art.–>central vn
Portal lobules=bile drain from hepatocyte to bile duct
:b/w caniculus central vn as pt. in lobules
Portal acinus=supplies O2 blood to hepatocyte
-dif. zone=Z1, Z2, Z3
:incre. O2 and nurtrients=Z1
:decre. O2 and nutrients=Z3
:incre. toxic affect=Z.3 b/c least support
normal liver-liver perfusion parenchyma is divided into how many lobules
3
Liver dis. response to injury
Hepatocytes -degen./intracellular accumulation -death= necrosis/apoptosis Inflammation Regeneration Fibrosis
Clinical Liver Syndromes
Hepatic Failure -no general functions -cells dnt function properly Cirrhosis -disrupt architecture -fibrosis w/ nodules of hepatocytes Portal HTN=incre. R to BF in liver Bilirubin metabolism failure
Can Cirrhosis maintain function and not know
Yes
Functional tissue nodules r suff. for maintenance
Greenish color=bile accum. (b/c bilirubin)
End stg. alcoholic liver~ cirrhosis resulting from other causes
Bilirubin Normally cleared
Senescent RBC r destroyed by phago.
-w/in spleen, liver, BnM
Color=yellowish
W/in fading bruises as RBCs from hemorrhage r removed
-hem brk dwn=produce billirubin (excreted by bile)
Not H2O soluble (pH=7.4)
Bound to albumin
Conj. Biliruben to glucoronic acid from excreted in bile=incre. solubility
-eventually fecal matter
-bile salts in bile is recycled
Bilirubin-abnormal
Cholestasis=impaired bile formation/flow
Incre. Bilirubin=jaundice and Icterus
The cells involved in fibrosis normal actions (when inhibit.)
Quiescent Stellate cel
-b/w space of disse=b/w endoth. and hepatocyte
-lipid droplet w/ vit. A storage
Inactive kupffer cell
Fibrosis pathogenesis
Foreign memb. comp.(carb/lipid) or secretion of memb. outter leaflet +MAC Release cytokine -prolif.=PDGF, TNF -contract=ET-1 -chemotaxis=MCP-1, PDGF Activation of stellate cells -+myofibrils prolif. -contraction -chemotaxis(influx comp.) -fibrogenesis=2ndry to +MAC
Causes hepatitis
Virus=infects hepatocytes
liver damage 2ndry to systemic infection
DONT need virus for hepatitis
Hepatitis-acute clinical synd.
Submassive hepatic necrosis
-Asymp.
:serological evidence
:acute w/ recovery
-Acute symptomatic hepatitis w/ recovery=anicteric or icteric
-acute liver failure=massive hepatic necrosis
Hepatitis-acute Pathology/pathogenesis
Pathology -necrosis (massive hepatocyte damage) Pathogenesis -lymphocyte infiltrate(mononuclear infiltrate) -hepatic damage -maybe bridging necrosis S/S -fatigue, decre. blood sugar, edema and decre. blood prot.
Hepatitis-chronic clincal synd.
Clinical synd.
-w/ or w/o progression cirrhosis
~ presentation to toxic liver injury
Hepatitis-chronic hep. pathology and pathogenesis
Pathology -end. stg. prog. hepatocyte damage -liver recovers from initial inj. Pathogenesis -dense mononuclear-infiltrate -bridging necrosis
Viral hepatitis-3 steps of expression
Virus infects hepatocyte
Hepatocytes express viral antGN
Immune system targets hepatocytes
Viral hepatitis-Cirrhosis is linked to which cancer
hepatocellular carcinoma
Viral hepatitis-acute and chronic basics
Acute -Primary viral=hepatitis A, B, C, D, E -Systemic viral (yellow fever, mononucleosis-EBV) Chronic=unresolved acute injury or from subacute injury -MC=hep. C -Mini.=Hep B/D -immunocomp.=Hep E -NEVER hep A
Viral hepA
2-6wks=fecal HAV -fecal oral infection 2-12 wks -anti-HAV IGM=decre. overtime -anti-HAV IgG Mo. to recover s/s=jaundice
Hep. B infection
1st acute infection -subclinical=recovery -acute hepatitis=recov. or falminant hepatitis (acute hep. fail) -death/transplant -Chronic :western=spont. clear of HbsAg :cirrhosis and/or hepatocellular carcinoma=death/transplant Histo -necrosis hepatocyte :also seen in hep. A -MAC cluster w/ eosinophilic cytoplasm Test -IHC for HbsAg -ground glass app. for HBsAg eosinophilic accum.
Hep C
Both acute and chronic -serum transaminase -2-26 wls=serum marker for HCV-RNA Acute -recovery w/ anti-HCV for mo. or years Chronic -no recovery -reactivate endogenous HCV strain -new mutant strains
Hep C-immune/histo.
Acidophil body=apoptotic cells
Mononuclear infiltrate=surrounding damage hepatocytes
Viral hep.-consequences
Loss liver function -hypoproteinemia -hyperbilirubinemia -anemia Infection/stress=more damage -cirrhosis may be undx
Chronic hepatitis symp.
S/S=fatigue, malaise, loss of appetite, mild jaundice Blood tests -Serum transaminase is elevated -Hyperglobulinemia -Hyperbilirubinemia Minor hepatomegaly/splenomegaly Hepatic tenderness Tx=symp. and allow it to pass
Drug and toxin liver injury-dis.
cholestatic cholestatic hepatitis -morphology :cholestasis w/ lobular necroinflammatory activity :may shouw bile duct destruction Hepatocellular necrosis -morphology-massive necrosis -assoc. =acetaminophen Fatty liver dis. -morphology=steatohepatitis w/ mallory-denk bodies -assoc. ethanol Fibrosis and cirrhoss -morphology=periportal and pericellular fibrosis -assoc. alcohol Neoplasms -morphology=hepatocellular carcinoma -assoc.=alcohol
Can you have both toxic and viral liver damage
Yes
Produce acute or chronic dis.
Immune response
Hepatocytes are destroyed=cirrhosis
B/C=liver is primary detox organ for the body
-toxins must be eliminated as a potential cuase
Toxic liver Injury
Z. 3=zonal necrosis Portal acinus=perfusion Toxins criteria -predictable/dose dependent Ej=acetaminophen very toxic to liver -idiosyncratic is not does dep. :Isoniazid (Tx TB) :Lovastatin(decre. cholesterol)
Toxic liver inj.-necrosis in liver
Necrotic liver -congested (expand BV and incre. blood -bile accum. -incre. necrosis not fibrosis [ :smaller liver :feel softer(should be tougher) Acetaminophen overdoes -confluent necrosis -zone 3 -surround central vn.
Common liver toxins-acetaminophen
Liver convert reactive intermed. -incre. cell killing in Z. 3 b/c less R to intermed Chlopromazine=dopa antag. -~ to acetaminophen -tx Schizo -form insoluble complex in bile :cholestasis in bile ducts -Metabolites :inhib. memb.-enzyme :improper function
Common liver toxin-ethanol w/ mild and serious injury
Mild injury=mod. alcohol intake(6 beer/8oz. of 80prof.) -liver inj. -steatosis=fatty deposit w/in liver -inhib. liver function -normally clear but accum. w/ chronic alcoholic intake Serious -massive intake/chronic effect -hepatitis
Toxic liver inj.-alcoholic hepatitis
Ethanol w/ multiple hepatocyte effect
-chemically=effect memb. function
:ethanol–>memb. =decre. memb. fluidity(ICF) and impair cell function
-induce/inhib. enzymes detoxying foreign comp.
:accum. foreign comp. and ROS(incre. O2 toxicity)
-Oxidation of Ethanol–>acetaldehyde
:inhib. prot. export/metab.
:alters redox potential
Toxic liver damage-alcoholic hepatitis hepatocyte damage
Necrosis=inflam infiltrate and visible fat pockets Mallory body formation -come from inhib. prot. degradation-- >IF prot. w/ ubiquitin -histologically=eosinophilic conc.
Toxic liver damage-alcoholic steatosis
Fat deposit w/in liver cell
Lrg/small fat droplets
MC around central vn in Z. 1
Toxic liver damage-alcoholic steatofibrosis
fibrotic changes from + steallet cell
Toxic liver Injury-for alcoholic hepatitis can steatosis, cirrhosis and hepatitis occur indi.
Yes BUT also in correlation from each other
Recovery w/ no alcoholic intake
Hepatitis-non alcoholic fatty liver dis.
80%=isolated fatty liver
-inhib. or decre. cirrhosis
-MAINLY steatosis
-no incre. risk of death compared to gen. pop.
Non-alcoholic steatophepatitis (NASH)
-prog. cirrhosis=hepatocell carcinoma or decom.
Hepatic vascular dis.-hepatic circulatory disorder (impaired blood inflow)
Inhib. BF/pre hep. Portal vn obstruction -intra/extrahepatic thombosis Manifestation -esoph. varieces -spleenomeg. -intesteinal cong.
histo. what is seen in sickle cell dis. and liver
occlusion of sinusoid
portal HTN causes
Prehep
-obstructive thrombosis of portal vn.
-structural abnorm. narrow of portal vn.
Intrahep.=anything incre. P.(mainly fibrosis.)
-cirrhosis of any cause
-Primary biliary cirrhosis (even w/o cirrhosis)
-massive fatty change
-diffuse, fibrosing granulomatous dis.(sarcoidosis)
-amyoidosis
Posthep.
-Cor pulmone
Where is liver found respective to thrombosi?
dwn stream from thrombosis while necrosis and hem is upstres
Preeclampsia/eclampsia-S/S
Maternal HTN
Proteinuria
Peripheral edema
Coag. abnorm. (hypercoag.)
Preeclampsia/eclampsia-liver dis manifestation as HELLP SYND.
H=hemolysis
EP=elevated liver enzymes
LP=Low platelets
(coag. impacted=fatal)
Preeclampsia/eclampsia-other S/S
Hemorrhage W/IN SPACE OF DIS
Fibrin deposits w/in periportal sinus
Develop coagulative necrosis of hepatocytes
Hematoma=under glisson’s capsulse(liver CT capsule)
-cn result in catastrophic hepatic rupture
BF to liver
portal vn.
can bilirubin damage liver?
Yes b/c excreted by liver
Cholestatic synd.
bile move. damage liver
Cholestatic synd.- Cholestasis and systemic retention of bilirubin and other solutes
Excess cholesterol Xenobiotics Other wast products NOT H2O soluble -cnt be eliminated in urine(h2o solb. goes to urine) -bile-->duodadenal and not absob=fecal
Cholestatic synd.- cholestasis and impaired bile formation and flow
Accum. of bile in hepatitis
Obstruction of bile channels (extra/intrahep.)
Defects in hepatocyte bile secretion
Cholestatic synd.- cholestasis and s/s
Jaundice=no inhib. biliruben Pruritis= bile sats deposit in skin -very itchy Skin xanthomas(cholest. accum.) Malabsop. -b/c no bile salts in duoad.=no absop. -no absop. of Vit. DEKA
Cholestasis-hist.
Enlarged hepatocyte
Dilated Canaliculus(channel b/w cells)
Apoptotic hepatocyte
Kupffer cells digest pig.
Cholestasis-acute larg duct obstruction
W/in hepatocellular parenchyma
Ductular rxn w/in PMN
Edema in portal tract stroma
NOT w/in caniculi
Cholestasis-caused by sepsis?
yes
Cholestasis-sepsis and the 3 diff. mech.
Diff. effects b/c infect w/in liver(abcess or cholangitis)
-cholangitis=bile duct lining is inflamed
-block bile flow
Circulating microbial products
-main cause leading to cholestasis(esp. gram neg.bact.)
Hypotension=ischemia(esp. if already cirrhotic)
Cholestasis-sepsis and commonly leading to canalicular cholestasis
Bile plugs w/in centrilobular bile canaliculi
+Kupffer cell
Mild portal inflam.
Cholestasis-sepsis and ductular cholestasis
Canal of hering is dilated an bile plugs in bile ductules
Edema/presence of PMN in stroma
Hepatocyte cell=death
Norm. gall bladder
Located=under liver and shares bile duct to go to duodenal
Food enter duodenal
-incre. bile by sphincter of odd into duodenal to mix w/ food
Dnt need bile
-goes to cystic duct and is store in gall bladder
:gall bladder store excess bile by special epith.
Cholecystitis-s/s
Inflammed gall bladder Acute or chronic or both Mainly assoc. w/ gall stones -incre. Bile conc. by ball bladder -cholesterol or pigment(bilirubin) stones
Cholecystitis-acute
Enlarged/tense gall bladder
Thick wall and fluid-filled (edematous)
Serosa=hem. under it
Fibrinous exudate coverage on gall bladder surface
-fibrinosuppurative(pus)=more severe dis.
Cholecystitis-Chronic
Mucosal inflam. infiltrate -incre. P. on wall forming sinuses Sinuses=rokitansky-aschoff sinus -disrupts muscularis of gall bladder -assoc. w/ prolife. of cells=PRE CANCEROUS LESION
Neuroendocrine tumors
Endocrine pancreas issues Benign -2% of pancreatic tumors -s/s relate to excessive hormone release Overgrowth of specific cell types(3 types) -Glucagonoma -Insulinoma -Somatostinoma
Neuroendocrine tumors-Glucagonoma
Alpha cells hyperplasia Glucagon=incre. gluco. Excessive gluc.=hyperglycemia S/S=Rash -malnutrition -AA--> to gluconegenesis not prot. production
Neuroendocrine tumors-insulinoma
beta cells hyperplasia Clinically -hypoglycemia=neuro sysmpt. -Incre. by fasting/excersi -incre. insulin=incre. gluc. uptake Tx=food/gluc.
Neuroendocrine tumors-somatostinoma
delat cells hyperplasia=inhib. alpha and beta cells
Diabetes=change gluc. uptake
cholethiasis=impaired bile secretion(gall stone)
Steatorrhea= inhib. pancreatic excretion (decre. glucagon)
-decre. fat brk dwn
Diabetes mellitus-insulin action
Adipose tissue -incre. gluc. uptake and lipogenesis -decre. lipolysis Striated muscle -incre. gluc uptake, glycogen/port. synth. Liver -decre. gluconeogenesis -incre. glycogen synth./lipogenesis
Diabetes mellitus- type I
Beta cell destroy -cn be absolute insulin def. Pathology -autoimmune rxn to islet beta cell(islet langerhan cells) -form insulitis
Diabetes mellitus-type II
Comb. of inulin R and B cell dysfunction
Pathology-Amyloidosis in islet
-cn be seen w/ normal age
-decre. islet cells
Pancreatic cells for a,b and d
alpha=glucagon
Beta-inulin
Delat=somatostatin
Diabetes mellitus-diabetic glomerulonephrophaty
diffuse mesangeial matrix incre. b/c endoth. uptake of gluc.
Incre. uptake by endoth. cells
-Hyperglycemia w/in insulin R=effect endoth. cell/function
-Incre. atherscloerosis
-Lipidemia=change function of (glycoprot.)
-Fibrinogen= thrombosis
Diabetes mellitus-clinically of no insulin or def./R
Pholyphagia
-incr. lipolysis(free FA)
-incre. prot. catoblisim(aa) w.in sk.muslce
-incre. glucagon
:gluconeogen
Hyperglycemia
-incre. gluconeogen
-insulin R.
-effect on endoth. cells=incre. renal vascular def.
:athrosclorsis
:dislipidemia after liver production of lipoprotein
:fibronolysis (incre. thrombosis)
Ketoacidosis=incre. lypolysis->ketogensis
-diabetic coma
Kid. issues from hyperglycemia and ketoacidosis
-ketonuria glycosuria
-polyuria
-volume depletion=polydispsia
:cn also cuases diabetic coma
exocrine pancreas dis.
Pancreatitis
Acute=reversible
Chronic=irrevers. exposure of unresolved acute damage that is not full resolved from prev. incidents
-cn be progressive and
Acute pancreatitis-CUASES
MC -Biliary tract dis.=b/c share the same duct ampuella w/ pancreas -Alcohol=MC -Toxin -Trauma -Vascular dis. Metabolic -mainly alcohol and drugs -hyperCa+emia and hyperlipoprotenemia Genetic=trypsin Mechanical -gallstone blocking the ampulla duct -Iatrogenic injury=surgery injury :endoscopic procedure w/ dye injection Vascular -shock b/c low BP Infection=mumps
Acute pancreatitis-pathogenesis
3 ways of the beginning -Ductal obstruction :ie gall stones :chronic alcohol -Acinar cell injury=alcohol -defective intracel transport=mainly alcohol All of them cause acinar cell injury Irreg. act. enzymes=causes acute pancreatitis
how is trypsin normally
An active pancreatic enzymes secretes and goes to duodenal to activate trypsin
Trypsin will active other enzymes
Acute pancreatitis-trypsin irreg.
Changes in assoc. w/ acute pancreatitis=autodigestion of pancreas by own digestive enzymes
Trypsin is activated in pancreas not duod.
-cuased mutation of cleavage site that usually deactivate(ie fail safe)
-mutation in trypsin inhib. =always active trypsin
Acute panreatitis-autodigestion
Elastase damages vsl walls=Microvasc. leakage(edema)
Activate lipases=fat necrosis
Proteases(trpsin, chemotryps etc.)=parenchymal degrade
Clotting defect.=thromboses damage wk vessl
Kallikrein=hem
-type of kinin
-related to BP and inflammation
-envolve plasma=degrad clots and +clotting factors
Acute pancreatits=pancreatic necrosis
Focal Parenchymal necrosis
Fat necrosis
Chronic pancreatitis-basic
Inflammation and irrev. destruction of acinar cells Fibrosis impact endocrine parenchyma -affect alpha, beta and delta cells MC=long term alcohol abuse -incre. excretion-->duct obstruction -directly toxic to acinar cells
Chronic pancreatitis -pathogenesis
~acute=duct obstruction and cell inj. Oxidative stress Repeated acute episodes=fiborsis and parenchyma loss -pelilobular fibrosis -duct distortion -altered secretion
Chronic pancreatitis -pathology
Parenchymal fiborsis
Reduce exocrin acini (not endocrin islets)
Duct dilation/conc.
Hepatic vascular dis.-hepatic circulatory disorder (impaired intrahepatic BF)
Inhib. intrahepatic BF Cirrhosis Sinusoid occlusion Manifestation -acites=2ndry to cirrhosis by accum. of fluid b/c assoc. w/ hypoalminemia from liver damage(no edema) -esophageal varices(cirrhosis) -hepatomegaly -elavated aminotransferases
Clinical pancreatitis
Upper abdo pain. -b/c inflam pancreas. (behind stomach) Nausea Vomit Fever Tachycardia Sweating Icterus/jaundice=gall bladder of ampula
Pancreatitis-tx
IV fluid
No food b/c activate pancreatic enzymes
Med. for pain/suppor
Hepatic vascular dis.-hepatic circulatory disorder (Hepatic vn. outflow obstruction-post hep.)
Hepatic vn. Thrombosis (bud-chirai synd.) Sinsusoidal obstruction synd. Manifestation -ascites -hepatomeg. -elevated= aminotrasnferase -jaundice
