digestive disorderas Flashcards
1
Q
Normal Liver-stroma
A
Reticular fibers
- chomphor cell
- eto cell
- endoth. cell
2
Q
Normal Liver-parenchyma
A
Hepatocytes -lrg cells w/ lots of organelles -stem cells like=Divide/regen. during lost hepatocyte -Function :detox :bile production :blood prot. :glycogen storage
3
Q
Normal liver-received blood from which organ
A
Directly from GIT
-perfusion determine susceptibility to toxin
4
Q
Normal liver-vasculature and system
A
Supportive via proper hepatic artery
Incre. O2 level
5
Q
Normal Liver-Vasculature function
A
Digestive tract
Via Portal Vn=incre. Nutrients
6
Q
Normal liver-blood flow
A
Blood–>sinusoid-parenchyma(b/w hepatoxyte) –>central vn(sublobular vn–>hepatic vn–>exit liver)
7
Q
Normal liver-portal triad
A
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)
8
Q
Normal liver-liver perfusion
A
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
9
Q
normal liver-liver perfusion parenchyma is divided into how many lobules
A
3
10
Q
Liver dis. response to injury
A
Hepatocytes -degen./intracellular accumulation -death= necrosis/apoptosis Inflammation Regeneration Fibrosis
11
Q
Clinical Liver Syndromes
A
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
12
Q
Can Cirrhosis maintain function and not know
A
Yes
Functional tissue nodules r suff. for maintenance
Greenish color=bile accum. (b/c bilirubin)
End stg. alcoholic liver~ cirrhosis resulting from other causes
13
Q
Bilirubin Normally cleared
A
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
14
Q
Bilirubin-abnormal
A
Cholestasis=impaired bile formation/flow
Incre. Bilirubin=jaundice and Icterus
15
Q
The cells involved in fibrosis normal actions (when inhibit.)
A
Quiescent Stellate cel
-b/w space of disse=b/w endoth. and hepatocyte
-lipid droplet w/ vit. A storage
Inactive kupffer cell
16
Q
Fibrosis pathogenesis
A
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
17
Q
Causes hepatitis
A
Virus=infects hepatocytes
liver damage 2ndry to systemic infection
DONT need virus for hepatitis
18
Q
Hepatitis-acute clinical synd.
A
Submassive hepatic necrosis
-Asymp.
:serological evidence
:acute w/ recovery
-Acute symptomatic hepatitis w/ recovery=anicteric or icteric
-acute liver failure=massive hepatic necrosis
19
Q
Hepatitis-acute Pathology/pathogenesis
A
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.
20
Q
Hepatitis-chronic clincal synd.
A
Clinical synd.
-w/ or w/o progression cirrhosis
~ presentation to toxic liver injury
21
Q
Hepatitis-chronic hep. pathology and pathogenesis
A
Pathology -end. stg. prog. hepatocyte damage -liver recovers from initial inj. Pathogenesis -dense mononuclear-infiltrate -bridging necrosis
22
Q
Viral hepatitis-3 steps of expression
A
Virus infects hepatocyte
Hepatocytes express viral antGN
Immune system targets hepatocytes
23
Q
Viral hepatitis-Cirrhosis is linked to which cancer
A
hepatocellular carcinoma
24
Q
Viral hepatitis-acute and chronic basics
A
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
25
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
```
26
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.
```
27
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
```
28
Hep C-immune/histo.
Acidophil body=apoptotic cells
| Mononuclear infiltrate=surrounding damage hepatocytes
29
Viral hep.-consequences
```
Loss liver function
-hypoproteinemia
-hyperbilirubinemia
-anemia
Infection/stress=more damage
-cirrhosis may be undx
```
30
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
```
31
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
```
32
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
33
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)
```
34
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.
```
35
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
```
36
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
```
37
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
38
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.
```
39
Toxic liver damage-alcoholic steatosis
Fat deposit w/in liver cell
Lrg/small fat droplets
MC around central vn in Z. 1
40
Toxic liver damage-alcoholic steatofibrosis
fibrotic changes from + steallet cell
41
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
42
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.
43
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.
```
44
histo. what is seen in sickle cell dis. and liver
occlusion of sinusoid
45
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
46
Where is liver found respective to thrombosi?
dwn stream from thrombosis while necrosis and hem is upstres
47
Preeclampsia/eclampsia-S/S
Maternal HTN
Proteinuria
Peripheral edema
Coag. abnorm. (hypercoag.)
48
Preeclampsia/eclampsia-liver dis manifestation as HELLP SYND.
H=hemolysis
EP=elevated liver enzymes
LP=Low platelets
(coag. impacted=fatal)
49
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
50
BF to liver
portal vn.
51
can bilirubin damage liver?
Yes b/c excreted by liver
52
Cholestatic synd.
bile move. damage liver
53
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
```
54
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
55
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
```
56
Cholestasis-hist.
Enlarged hepatocyte
Dilated Canaliculus(channel b/w cells)
Apoptotic hepatocyte
Kupffer cells digest pig.
57
Cholestasis-acute larg duct obstruction
W/in hepatocellular parenchyma
Ductular rxn w/in PMN
Edema in portal tract stroma
NOT w/in caniculi
58
Cholestasis-caused by sepsis?
yes
59
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)
60
Cholestasis-sepsis and commonly leading to canalicular cholestasis
Bile plugs w/in centrilobular bile canaliculi
+Kupffer cell
Mild portal inflam.
61
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
62
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.
63
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
```
64
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.
65
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
```
66
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
```
67
Neuroendocrine tumors-Glucagonoma
```
Alpha cells hyperplasia
Glucagon=incre. gluco.
Excessive gluc.=hyperglycemia
S/S=Rash
-malnutrition
-AA--> to gluconegenesis not prot. production
```
68
Neuroendocrine tumors-insulinoma
```
beta cells hyperplasia
Clinically
-hypoglycemia=neuro sysmpt.
-Incre. by fasting/excersi
-incre. insulin=incre. gluc. uptake
Tx=food/gluc.
```
69
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
70
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
```
71
Diabetes mellitus- type I
```
Beta cell destroy
-cn be absolute insulin def.
Pathology
-autoimmune rxn to islet beta cell(islet langerhan cells)
-form insulitis
```
72
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
73
Pancreatic cells for a,b and d
alpha=glucagon
Beta-inulin
Delat=somatostatin
74
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
75
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
76
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
77
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
```
78
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
```
79
how is trypsin normally
An active pancreatic enzymes secretes and goes to duodenal to activate trypsin
Trypsin will active other enzymes
80
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
81
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
82
Acute pancreatits=pancreatic necrosis
Focal Parenchymal necrosis
| Fat necrosis
83
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
```
84
Chronic pancreatitis -pathogenesis
```
~acute=duct obstruction and cell inj.
Oxidative stress
Repeated acute episodes=fiborsis and parenchyma loss
-pelilobular fibrosis
-duct distortion
-altered secretion
```
85
Chronic pancreatitis -pathology
Parenchymal fiborsis
Reduce exocrin acini (not endocrin islets)
Duct dilation/conc.
86
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
```
87
Clinical pancreatitis
```
Upper abdo pain.
-b/c inflam pancreas. (behind stomach)
Nausea
Vomit
Fever
Tachycardia
Sweating
Icterus/jaundice=gall bladder of ampula
```
88
Pancreatitis-tx
IV fluid
No food b/c activate pancreatic enzymes
Med. for pain/suppor
89
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
```
