Exam 2 Flashcards
(444 cards)
1
Q
why do people turn yellow with jaundice
A
due to disease product bile leaks into blood and patients look yellow
2
Q
how heavy is liver
A
1.5 kg
3
Q
what is glisson’s capsule
A
thin CT capsule deep to mesothelium around the entire liver
4
Q
blood supply to liver (2) and route in liver
A
- hepatic artery from aorta - supplies 25% of blood - highly oxygenized
- portal vein - supplies 75% of blood - poorly oxygenated, nutrient rich
they mix in sinusoids, drain into central veins in the middle of lobules, and then trains into hepatic veins into the iVC
5
Q
components of portal triad
A
branch of portal vein, branch of hepatic artery bile duct
6
Q
what’s a portal lobule?
A
roughly triangular with central veins at three corners and portal triad in the middle - emphasizes production of bile
7
Q
what’s the hepatic acini lobulation structure
A
diamond shaped with central veins and two ends and portal triads at middle ends - emphasizes blood flow
zone 3 is closest to central vein - recieves least oxygenated blood
zone 1 is closest to portal triad, gets damaged first by toxins
8
Q
what kind of epithelium does bile duct have
A
simple cuboidal
9
Q
kupffer ceclls
A
fat, phagocytic cells lining hepatic sinusoids
10
Q
ito cells
A
store vitamin A
11
Q
space of disse
A
between endothelium and hepatic parechymal cels - only see on EM
12
Q
gall bladder histology
A
- mucosa (no muscularis mucosae) has foldings
- tall columnar abosrptive cells NO GOBLET CELLS
- inner thick circullar, variable outler long
- in neck, some mucous secreting cells in submucosa
- mostly serosal, but neck is retroperioteal - adventitia
13
Q
capillaries in pancreas - where are they open and where are they closed
A
closed in exocrine (enzymes), open in endocrine (hormones)
14
Q
alpha and beta cells - what do the produce and where do you see them in light microscope
A
alpha- glucagon
beta - insulin
alpha smaller darker and peripheral
beta larger lighter and central
15
Q
centroacinar cells
A
cell between acinus and intercalated duct
16
Q
names of ducts (and epithelium type) from acinus to end of pancreas (4)
A
1- intercalated ducts (centroacinar cells at tips)
2- intralobular (cuboidal)
3- interlobular (low columnar)
4- main pancreatic (low columnar)
17
Q
is pancreas mostly endocrine or exocrine
A
exocrine
18
Q
what stimulates pancreatic enzyme secretion and through what pathway (5)
A
Calcium mediated:
CCK
ACh
GRP
cAMP mediated:
VIP
Secretin
19
Q
salivary versus pancreatic secretions - hypo hyper or iso osmotic
A
salivary is hypo, pancreatic is iso
20
Q
what transporters maintain gradient to pump bicarb out of pancreas (3)
A
- basolateral sodium bicarb co transporter
- basolateral sodium potassium ATPase
- apical CFTR chloride channel
21
Q
phases of pancreatic secretion (4)
A
- basal - 10% enzyme secretion into acini
- cephalic - neural signals, thinking about eating, Ach from vagus, increases enzyme secretion 20%
- gastric - also Ach release by vagus from neural signals strech receptors, only 5% enzyme secretion
- intestinal - 70% of excretion - copious in response to chyme in small intestine - CCK, Secretin, Ach and VIP (enteropancreatic reflex)
22
Q
at what pH is secretin released
A
below 4.5
23
Q
what are the primary bile acids (2), secondary bile acids (2) and bile salts (2)
A
primary (after 7alpha hydroxylase from cholesterol):
cholic acid
chenodeoxycholic acid
secondary (after bacteria does 7alpha dehydroxylase): deoxycholic acid (from cholic) lithocholic acid (from cheno)
bile salts:
taurine
glycine
24
Q
bile salt independent flow regulators (3)
A
- increased in response to secretin
- opposed by somatostatin
- comprised of secretion of bicarb, absportion of Na and Cl
25
sodium dependent bile acid transporters - what do they transport into the cell?
1. IONIZED unconjugated/free
bile acids
2. conjugated bile acids (ionized or not)
26
how does gut talk to the liver?
bile acids increase in ileal lumen
acids bind nuclear receptor FXR in ileal enterocyte and dimerizes with RXR
downstream gene expression of FGF19 increases
FGF19 gets into blood stream to liver, which gets to hepatocyte
FGF19 then inhibits CYP7A1 which in turn shuts down synthesis of 7alpha hydroxylase - rate limiting step in bile acid synthesis
27
when does glucuronidation happen
secondary bile acids are not good to have around, so they get glucuronidated
28
why is poop brown
conjugated bilirubin from liver gets converted via bacteria to urobilinogen, then to stercobilinogen, and then to stercobilin which is brown
29
why is pee yellow
urobilinogen gets oxidized to urobilin which is yellow
30
how does bilirubin get into hepatocyte
via OATP
31
how does bilirubin get into bile
conjugated to glucuronic acid via general transport MRP
32
jaundice in infants
(UGT) UDP-glucuronyl transferase reduced in infants
33
hemolytic jaundice - what kind of bilirubin do you see
lots of unconjugated bilirubin
34
obstructive jaundice- what kind of bilirubin do you see
lots of conjugated bilirubin
35
where does ammonia come from? (3)
50% from colon - bacterial ureases and AA metabolism
40% from kidneys - glutamine metabolism
red from RBC and muscle
36
which is caudate and which is quadrate
quadrate = with gall bladder
37
cystic artery comes off of what, and where is it
right hepatic, in the triangle between common hepatic duct and cystic duct and liver
38
branches if iMA
left colic - to descending colon and up to splenic flexture - then meets up with marginal artery
sigmoid arteries - to sigmoid colon (2-4 arteries)
superior rectal artery
39
ligament of treitz - AKA, where is it, what does it come from
suspensory ligament of duodenum - holds up the 4th part of duodenum, under the pancreas - from right crus of diaphragm
40
what does left crus of diaphragm do
nothing special
41
what part of pancreas is intraperitoneal
tail next to spleen
42
what vessel is the neck of the pancreas laying over
SMA
43
what structures are posterior to the SMA
unctinate process of pancreas and duodenum
44
hepatic portal vein components
union of smv and splenic vein
45
inferior mesenteric vein dumps into where usually
splenic vein
46
in what part of the duodenum does bile enter into
2nd part
47
why do women get gallstones more than men
high estrogen states makes bile precipitate
48
why do you get referred pain
general somatic and visceral nerve fibers converge on same spinal neuron - brain gets confused where pain is actually coming from
49
extra GI manifestations of gallbladder obstruction
- scleral icterus, jaundice and yellowing frenulum
- abdominal tenderness (somatic localized or visceral diffuse pain)
- mass (distended gall bladder, neoplasm)
50
murphy's sign
acute cholecystitis -
51
cullen's sign and grey-turner
flank, peri-umbilical ecchymosis/ bleeding
| - hemmorhhagic pancreatitis
52
boas sign
irritation heightened sensation in scapular region - referred pain T6-T8
53
rebound tenderness
peritoneal inflammation
54
lab data for gallbladder obstruction (3)
total and direct bilirubin (Extrahepatic obstrution)
gamma glutamyl transpepeitase (Extrahepatic)
amylase rises earlier in pancreatitis, lipase rises later
55
is normal gallbladder hypo or hyper echoic
hypo, hyper would indicate stones (stones also have shadows behind)
56
acute cholecystitis on US (2)
obstruction causes contraction and thickening of the wall
increased bile density - super saturated
57
fat stranding on CT - what does it indicate
haziness - indicates inflammation
58
HIDA scan
hepatobiliary iminodiacetic acid - tracer attaches to anywhere with bile. want to see if it's emptying completely
59
cystic duct obstruction
| lab values
normal LFTs and normal pancreatic enzymes
60
when do you get gangrenous changes in gallbadder
if you let acute cholecystitis go on too long
61
what oxidation state of iron can cross through membranes
+2
62
what oxidation state is stored as ferritin
+3
63
which oxidation state of iron is more dangerous
+2
64
how do you go from transferrin outisde of cell to iron inside cell
transferrin receptor is endocytosed, acidified, transerrin releases +3 iron, which is reduced to +2, transported out of endosome and used, any extra is stored as +3 in ferritin
65
heme biosynthesis steps (feedback and rate limiting) (4)
1. glycine +succinyl-CoA makes 5ALA (via 5ALA synthase - rate limiting step in LIVER) feedback inhibition by hemin (+3 oxidized heme) and lead (replaces zinc cofactor)
2. 2 molecules of 5ALA get converted to porphobilinogen via 5ALA dehydratase
3. 4 molecules of porhobilinogen get converted to uro-porphyrinogen 3 somewhat spontaenously
4. Uro-porphyrinogen 3 then becomes protoporhyrin 9 - and ferrochelatase inserts iron into ring structure and makes heme (rate limiting in RBCs, inhibited by lead)
66
what does 5ALA synthase do and what do you get if it's deficient
makes 5ALA from glycine and succinyl co-a
get X-linked sideroblastic anemia
67
what does ALA dehydratase do and what do you get if it's deficient
takes 2 ALA and makes porphobilinogen
get ALA dehydratase deficient porphyria
68
what does PGB deaminase do and what do you get if it's deficient
takes 4 porphobiliogen into hydroxymethylblaine
get acute intermittent porphyria
69
what does uroporphyrinogen 3 synthase do and what do you get if it's deficient
takes hydroxymethylblaine and makes uroporphyrinogen 3
get congenital erythropoetic porphyria
70
what does uroporphryinogen decarboxylase do and what do you get if it's deficient
takes uroporphyrinogen 3 and makes coproporphyrinogen 3
get porphyria cutanea tarda
71
what does coporporhyrinogen oxidase do and what do you get if it's deficient
takes coproporphyrinogen 3 and makes protoporphyringoen 9
get hereditary coproporphyria
72
what does protoporhyrinogen oxidase do and what do you get if it's deficient
takes protoporphyrinogen 9 and makes protoporphyrin 9
get variegate porphyria
73
what does ferrochelatase do and what do you get if it's deficient
adds iron to protoporphryin 9 and makes heme b
get erythropoetic protoporphyria
74
which steps in heme biosynthesis happen in mitochondria
first and last 3:
enzymes:
1. 5ALA synthase
2. coproporphyrinogen oxidase
3. protoporphyringen oxidase
4. ferrocheletase
75
what happens with water, sunlight and conjugated double bonds
make free radicals - peroxides etc.
76
what kinds of porphyria are considered acute (3)
1. acute intermittent
2. variegate
3. hereditary coproporphyria
77
what are symptoms of acute porphyria (5)
1. ab pain
2. purple skin rashes
3. red urine
4. muscle weakness
5. psychotic episodes
inducible expression
78
what kinds of porphyria are considered chronic (3)
1. congenital erythropoeitic porphyria
2. porphyria cutanea tarda
3. veriegate porphyria
79
chronic porphyria symptoms (4)
1. derm issues (light sensitive, blistering)
2. red urine, blue urine
3. werewolf syndrome - fine hair body-wide, light sensitive
4. vampire syndrome - red fluorescent teeth and gums, light sensitivity AND can't eat garlic for GI issues
80
tx for acute porphyria
hemin - feedback inhibition of ALA synthase
81
what oxygenation state likes to bind to cyanide
+3 - methemoglobin
82
what helps RBCs off load more oxygen
rapaport luebering shunt - stabilizes deoxygenated state
83
Glucose 6 phospate dehydrogenase deficiency
quinine generates free radicals - causes hemolytic anemia
84
what mechanisms are in place to reduce organ damage with hemolysis (2)
haptoglobin - complexes with hemoglobin from lysed RBCs to protect kidney filtration
hemopexin - binds free heme or hemin to generate free radicals
85
what oxygen state is the iron in hemin
+3
86
what happens to hemoglobin in macrophage, once RBC is internalized?
hemoglobin gets broken down into hemin and globin
hemin gets converted to biliverdin via heme oxygenase with NADPH (produces CO)
biliverdin gets converted to bilirubin via biliverdin reductase and NADPH
87
structural difference between biliverdin and bilirubin
verdin is green - has double bonds, is linear, modestly soluble - can interact with water
rubin - 4 single bonds, can rotate and fold back on itself - not soluble, needs to be transported via albumin to the liver to get glucuronidated to make it soluble
88
what's the enzyme that's deficient in neonates
glucuronosyl transferase
89
why does phototherapy work for neonatal jaundice
light (blue especially) converts unconjugated bilirubin into isomeric form (bilverdin) the the liver can kick to bile
90
van den bergh reaction equation
total bilirubin (indirect reacting) - conjugated bilirubin (direct reacting) = unconjugated bilirubin
91
stellate cells - where are they, what do they do
in spce of disse, store vitamin A in quiescent state, activated cells become myofibroblasts that make collagen - for scar formation in liver damage
92
what proteins does the liver make (2)
albumin and most clotting factors
93
when does jaundice become visible
when bilirubin is 2x normal in adults, or 5x normal in neonates
94
halflife of bilirubin-dicluronide, vs bilirubin and biliprotein
biliprotein halflife is 20 days versus 1 day for bili-diglucuronide
95
how to measure direct and indirect
direct measures conjugated - turns serum blue - how much blue, then accellerant is added, and then you measure the rest - then get total
96
prehepatic - what kind of bilirubinemia do you get
increased all uncojugated
97
hepatic- what kind of bilirubinemia do you get
elevated in both - prevents unconjugated from excreting and conjugated from being conjugated
98
post-hepatic - what kind of bilirubinemia do you get
at first, you have increase of conjugated, but then you start to see increases in conjugated too - cause hepatocyte damage eventually
99
cause of pre-hepaitc hyerbilirubinemia
1. hemolysis, transfusion
2. decreased albumin-bilirubin binding
3. decreased hepatocyte internalization
last two affect neonates - physiologic jaundice, can lead to kernicterus - treat with UV light or phenobarb
100
parenchymal causes of hyperbilirubinemia (5)
high unconj:
1. Gilberts
2. Crigler-Najjar type 1
both:
3. Cirgler-Najjar type 2
more conj than unconj:
4. cirrhosis
5. hepatitis
101
enzymes that indicate bile stasis (2)
1. alk phos (7 day half-life)
2. gamma-glutamyl transferase (26 day half-life) - indirect marker of alcohol abstinence
if both are increased, indicates damage to cannalicular membranes. if just alk phos, could be bone, placenta etc.
102
decrease in albumin might mean acute or chronic liver problem
chronic - half life is 20 days
103
increased prothrombin time indicates what kind of liver problem
in acute, severe liver injury - half life is 6 hours (depends on vitamin K - give vitamin K to see if it resolves)
104
liver transaminase half-lives
cytosolic ALT is 48hours
cytosolic AST is 8 hours
mithochondrial AST is 10 days
lactate dehydrogenase - 4-6hours
105
acute, abrupt liver injury - which transaminase is higher
AST is higher, much more of it in liver cell than ALT
106
lower grade and sustained liver injury - which transaminase is higher
ALT is higher - longer half life
107
alcohol-related liver injury - which transaminase is higher
AST is higher than ALT - alcohol inhibits ALT synthesis
108
injury versus function enzymes
bilirubin, albumin and PT are liver fucntion
AST and ALT and alk phos are mark of injury
109
congeintal anolomalies in gall bladder (6)
1. sometimes under left lobe
2. cysts and 3. diverticulae
4. septate gallbladder, multpile gallbladders
5. heterotopia - normal tissue in abnormal location- pancreatic tissue in wall of gallbladder
6. hypoplasia
110
cholesterolosis
red-tinged with yellow stippling- foamy macrophages with cholesterol esters deposited in lamina propria
111
composition difference between cholesterol and pigmented stones
cholesterol has more than 50% cholesterol component
112
different risk factors for choletsterol stones
high fat, age, female gender, pregnancy, obesity, bile stasis
113
risk factors for pigmented stones
heredity
helolytic syndrome
biliary infectinos
GI diseases - chrohn's etc.
114
what do you see in gross for acute cholecystitis? (3)
1. hemorrhage
2. edema
3. mucosal ulceration
115
what do you see in histo for acute cholecystitis
1. fibrin exudate
2. neutrophils
3. hemorrhage that can extend through wall and be necrosis
116
chronic cholecystitis gross findings (1)
thickening of wall
117
chronic cholecystitis histo findings (5)
1. Rokitansky-Aschoff sinuses (look like diverticuli)
2. SM hypertrophy
3. lymphocytic infiltrate
4. granulomas +/-
5. hyperplastic or metaplastic epithelium
118
follicular cholecystits findings and associations (3)
lymph follicles in gallbladder, associated iwth primary sclerosing cholangitis, typhoid and gram neg bacterial infection
119
xanthogranulomatous cholecystitis findings (5)
1. foamy macrophages
2. cholesterol clefts
3. extruded bile
4. multinucleated giant cells and neutrophils
5. thickening of wall with yellow-brown nodules
120
hyalinizing cholecystitis findings and associations (1)
1. replacement of gallbladder wall by hyalinized fibrosis
| 2. associated with occult adenocarcinoma
121
gallbladder tumors (4)
1. benign (adenomyoma)
2. polyps (cholesterol non-neoplastic, adenoma papillary neoplasms)
3. epithelial dysplasia (biliary intraepithelial neoplasia)
4. malignant adenocarcinoma
122
where/when are adenocarcinomas usually found
in fundus and body more so than the neck in older female with stones, esp in south america
123
What parts of the pancreas come from which embryological structures "buds"
ventral bud (from hepatic duct) - forms posterior/inferior head and uncinate process
dorsal bud (From foregut) - forms body, tail and anterior head
124
congenital pancreatic disorders (4)
1. annular pancreas around 2nd part of duodenum
2. divisum - failure of duct fusion (2 ducts) associated with cancers
3. heterotopic pancreas (tissue from pancreas in stomach, duodenum, jejunum)
4. metabolic disorders
125
acute pancreatitis gross/histo findings (4)
1. interstitial edema
2. hemorrhage
3. necrosis (and fat necrosis)
4. pancreatic pseudocysts
126
chronic pancreatitis findings gross and histo (3)
1. loss of parenchyma - replaced by fibrosis and fat tissue
2. chronic inflammation around lobules and ducts (sparing islets)
3. can mimic a pancreatic mass
127
causes of chronic pancreatitis (6)
1. genetic (CFTR)
2. toxic (calc, lipid, alcohol, smoking, hydrocarbons, drugs -thiazides)
3. obstruction
4. autoimmune
5. infectious
6. other (radiation, post-transplant)
128
pseudocyst composition
no epithelial lining, fillled with turbid, blood tinged fluid = necrotic debris, inflammation, hemorrhage, walled off by fibrosis sometimes
129
pancreatic tumors (4)
most are malignant and solid:
1. ductal adenocarcinoma
2. neuroendocrine tumors
3. anaplastic carcinoma
4. acinar cell carcionma
130
panIN
less than 5mm
dysplasia in cysts in pancreas - benign pancreas
grade by low and high - becomes more papillary and enlarged nuclei that lose polarity
131
pancreatic neuroendocrine tumor types and grading
"functional" - have clinical presentation (insulinoma - fainted, irregular heart rate)
"non functional" - no clinical presentation (usually found more advanced)
grading (3) based on mitotic count and IHC
132
anaplastic carcinoma characteritsics (4)
undifferentiated, large eosinophilic cells
rare
poor porgnosis
133
acinar cell carcinoma characteristics (3)
1. metastatic at presentation
2. syndrome of lipase hypersecretion - polyarthralgias, fat necrosis, peripheral eosinophilia
3. sheet of acinar cells
134
serous cystadenoma characteristics (4)
1. benign neoplasm (but may metastasize)
2. central stellate scar with surrounding cysts
3. cysts lined by cuboidal epithelium
4. associated with VHL gene mutation
135
solid pseudopapillary neoplasm - characteristics (4)
1. seen in young females
2. well circumscribed mass with solid and necrotic parts
3. on histo - papillary with fibrovascular cores
4. associated with beta catenin gene mutation (CTNNB1)
136
mucinous cystic neoplasm (4)
1. more freqently in females
2. mucious material and epithelium
3. wall looks like ovary (spindled stroma)
4. associated with KRAS and secondary mutations later
137
intraductal papillary mucinous neoplasm findings (4)
1. more in men
2. mucinous materal and epithelium
3. are associated with pancreatic duct
4. KRAS and/or GNAS mutations
138
what do mets to the pancreas look like
multiple (intrinsic tumors tend to be solitary) well circumscribed masses
139
are cholesterol stones seen on xray?
no - low calcium
140
what kind of bilirubin is in pigmented stone
unconjugated
141
do you see pigmented stones on xray?
yes
142
which kind of stones are infectious
brown pigmented stones (E. coli)
143
what kind of stones are seen in hemolysis and sickle cell
black pigmented stones
144
why does rapid weight loss result in gall stones
lipids go down, so abnormal composition in bile - get bound to calcium and form stones
145
charcot's triad
RUQ pain, fever, jaundice
146
reynolds pentad
charcot's triad plus sepsis and mental status changes
147
how big is ileocecal valve - aka what size stones will cause obstruction
15mm
148
when do you intervene in sphincter of oddi dysfunction
you need to have at least either abnormal liver enzymes or abnormal biliary imaging, biliary type pain is not sufficient
149
causes of acute pancreatitis (6)
1. stones
2. alcohol
3. trauma
4. post-op
5. meds (steroids, estrogens, HIV meds, antibiotics)
6. high triglycerides (over 1000) and calcium
150
what can kill you with acute pancreatitis (2)
ARDS
| splenic artery rupture
151
what 2 out of 3 things do you need to indicate acute pancreatitis
1. ab pain
2. CT findings
3. abnormal lab work (increased lipase and amylase)
152
how bad does chronic pancreatitis have to get to cause steatorrhea and fat malabsorption?
have to burn through 90% of exocrine function
153
fecal elastase indication
if low, then it indicates poor exocrine pancreas function
154
how does chronic pancreatitis sx work (peustow's, frey, whipple)
slice pancreas like a sausage, put part of the intestines in there - decreased ductal pressure
155
how likely are people with chronic pancreatitis to get cancer
4x more likely
156
primary biliary cholangitis associations/patient demographic
1. 30-65 age
2. female predominance
3. associated with thyroid and autoimmne
157
primary biliary cholangitis physical exam and symptoms (8)
1. pruritis
2. fatigue
3. hyperpigmentation
4. xanthelasma (deposits on eyelids)
5. dry eye and mouth (sicca syndrome)
6. jaundice
7. excoriations from itching
8. hepatosplenomegaly
158
what do you do when someone has elevated alk phos
elevated ggtp and 5nt - indicate liver
if liver, go over drug list, AMA (primary biliary cholangitis) ACE (sarcoidosis) RUQ US
159
primary biliary cholangitis lab findings (5)
1. elevated alk phos
2. AMA pos (95%)
3. ANA pos (70%)
4. elevated IgM
5. elevated cholesterol and lipids
160
histo findings for primary biliary cholangitis (3)
1. "florrid" interlobular duct lesions - inflammation around duct (plasma cells, macrophages, eosinophils)
2. granulomas if present are highly indicative
3. eventual fibrosis which leads to cirrhosis
161
treatment for primary biliary cholangitis (2)
ursodeoxycholic acid - which increases bile flow and decreases toxic/hydrophobic bile acids by replacing with more hydrophilic and antinflammatory bile acids
cholestyramine for pruritis (bile acid sequestrants)
162
primary sclerosing cholangitis associations/patient demographics (4)
1. mean age 41
2. 70% male
3. 80% have UC
4. maybe bacterial infection
163
what size ducts are affecting in primary sclerosing cholangitis
medium and large (as opposed to biliary cholangitis - which is interlobular and small ducts)
164
symptoms of primary sclerosing cholangitis (5)
1. RUQ pain
2. fatigue
3. pruritis
4. fevers, chills, night sweats
5. jaundice
165
lab findings in primary sclerosing cholangitis (3)
1. elevated alk phos
2. high IgG4 (steroid responsive) and IgM levels
3. P-ANCA positive
166
imaging findings for primary sclerosing cholangitis (3)
1. bile duct wall thickening and focal dilations
2. beaded appearance of bile duct (short strictures)
3. later, see obliterated ducts with strictures - "pruned tree" appearance
167
histo findings for pirmary sclerosing cholangitis
fibrous obliteration of small bile ducts - onion skinning pattern
168
treatment for primary sclerosing cholangitis
ursodeoxycholic acid - possible, not shown
management of symptoms and liver transplant (recurrence happens often at 5 years)
169
immune-mediated pattern of liver disease - timing of rise of enzymes
slow to rise over several weeks, plateaus and slowly resolves. usually prothrombin time is normal
170
direct toxic pattern - timing of enzymes
pulse injury - marked release in liver enzymes at once (AST higher at first), falls precipitously
171
alcohol related pattern - timing of enzymes
flat - inhibit the synthesis of enzymes to some extent
172
acute viral heptatis histology findings
red swollen liver
1. infiltrate in portal tract and in parenchyma
2. necrosis
3. drop out and apoptotic bodies
173
unpredictable drug reaction liver injury
parenchymal hepatitis that looks a lot like viral hepatitis
174
predictable drug reaction liver injury
see necrosis in zone 3 - looks like ischemia
175
alcohol hepatitis injury pattern
sudden acute liver fat accumulation and inflammation in zone 3 with BALLOON CELLS empty looking cells, and cells with fat globules, some have intermediate fillament aggregations in them (MALLORY BODIES)
176
ascending cholangitis on histology (5)
1. hepatocytes with feathery degeneration (xanthomatous degeneration)
2. bile infarcts/plugs
3. bile lakes
4. ductular proliferation
5. neutrophils
177
causes of chronic hepatitis (3)
1- viral (hep B and C)
2- autoimmune
3- drug-related
178
causes of metabolic chronic liver injury (3)
1- hemachromatosis
2- Wilson's disease
3- antitrypsin deficiency
179
causes of vascular chronic liver injury
1. venous outflow obstruction (Budd-Chiari)
| 2. CHF and ischemic necrosis
180
examples of chronic cholestatic syndromes (3)
1. partial extrahepatic obstruction
2. primary biliary cirrhosis
3. primary sclerosing cholangitis
181
clinical definition of chronic hepatitis (2)
ALT or AST >1.5X (ALT usually higher except for end stage and alcohol)
4-6 mo duration
182
histology of chronic viral hepatitis
zone 1 lymphocytic infiltrate and necrosis. more so in portal tract than parenycmal
183
top 3 causes of liver disease
1. hep B and C
2. alcohol
3. non-alcoholic (getting greater)
184
what is erosion of "limiting plate" on histo and when do you see it
limiting plate is boundary of portal triad - in chronic hepatitis you erode that limiting plate - interface hepatitis
activity grade = how much necrosis do you see
185
fibrous stages in chronic hepatitis
1. enlarged portain tract
2-3. bridges of fibrosis - portal to portal tract
4. cirrhosis encircling fibrosis around regenerative nodules of hepatocytes
186
clues to distinguish chronic hepatitis causes (3)
classic for viral is GROUND GLASS HEPATOCYTE - excess of surface antigen in endoplasmic reticulum - hep B
autoimmune - PLASMA CELLS
drug tox - EOSINOPHILS
187
who gets autoimmune hepatitis
mostly European females, bimodal age distribution, half have extrahepatic autoimmune disease
188
diagnosis of autoimmune heptatitis - tests (3)
ANA (67%)
SMA (87%)
liver biposy (plasma cells)
189
tx for autoimmune hepatitis
steroid
190
what do you see with chronic ischemic fibrosis
chronic centrilobular fibrosis (zone 3)
191
risk factors for chronic liver ischemic/vascular congestion/necrosis
Budd Chiari:
1. young woman - oral contraceptives or pregnancy, and other hypercoaguable states
2. hepatocellular carcinoma
3. right heart failure- cor pulmonale
192
gross characteristic of chronic vascular congestion/necrosis/ischemia
NUTMEG LIVER - congestion and dilation in sinusoids
193
treatment for budd-chiari (3)
1. antithormbotics if quick enough
2. management of ascites
3. TIPS stent to relieve pressure
194
alpha-antitrypsin deficiency also causes
emphysema
195
genes involved in hereditary hemochromatosis
C282Y
H63D gene
196
extrahepatic manifestations of hereditary hemochromatosis (4)
1. cardiomyopathy
2. skin and pancreas - bronze diabetes
3. degenerative arthritis (does not resolve with tx)
4. low libido (pituitary - hypogonadism)
197
histo - hereditary hemochromatois
iron accumulation IN HEPATOCYTES (not just macrophages)
golden brown on H&E
can do prussion blue stain for positive
198
gene related to wilson's
ATP7B
199
when do you start to see copper in extrahepatic tissue
when liver is overwhelmed - probably already cirrhotic
can see movement disorders, RBC hemolysis, renal tubular acidosis, cornea
200
what's the best diagnostic test for wilsons
24hr urine copper excretion test is good
liver biopsy is gold standard
201
copper accumulation in histo
Rhodanine stain - red granules
202
alpha-antitrypsin deficiency gene
protease inhibitor PiZZ
203
histo finding for alpha antitrypsin
PAS diastase resistant red granules
204
difference between steatohepatitis and fatty liver disease
steatohepatitis has inflammatory component - worse- cause chronic damage
205
nonalcoholic steatohepatitis findings (lab)
ALT>AST (opposite for alcohol)
| 20% lead on to cirrhosis
206
treatment for nonalcoholic steatohepatitis
vitamin E
| weight loss and diabetic control
207
steatohepatitis gross presentation
"micronodular" cirrhosis (nodules less than 0.5cm
208
difference between forms of steatohepatitis on histo
mostly the same, but non-alcoholic has more lymphocytes, not so many neutrophils (as opposed to alcohol)
209
flroid duct associated iwth what
PBC
210
onion skin fibrosis of ducts associated with
PSC
211
how to make diagnosis of PSC
imaging
212
what about hepatocytes and sinusoids changes in cancer
hepatocytes are 1-2 cells thick so that every hepatocyte has access to sinusoid, even in cirrhosis, if that's disturbed then that indicates cancer
213
chronic cholestasis extrahepatic manifestations
pruritic rash
xanthelasma (on eyes)
xanthomata (on hands )
214
hepcidin role
normal hepcidin works to endocytose ferroportin transporters, thus decreases iron absorption
abnormal hepcidin (caused by HFE gene mutation) doesn't downregulate iron absoprtion, thus allowing for too much iron into the cells
215
lab values/test for hemochromatosis (2)
1. iron/TIBC >45%
2. ferritin >200 in men and 150 in women
if any of those are positive then do genetic screening (for H63D and C282Y)
216
goal of phlebotomy in hemochromatosis
get ferritin less than 50
217
what should people with hemochromatosis NOT do (3)
1. take iron supplements
2. drink alcohol
3. get cirrhotic - higher chance of cancer
218
patient presents with mental status changes, hemolysis and increased liver enzymes
Wilson's
219
why does Wilson's lead to hemolysis
copper damages RVC cell membrane
220
what lab values/tests do you look for in wilsons
low ceruloplasmin (ceruloplasmin bound to copper does not show up - meaning there's a lot of copper)
urine 24hour commer excretion
221
tx for wilson's (3)
Chelation:
D-penicillamine (EXCEPT in mental status change)
Trientine (in mental status changes)
oral zinc - decreases copper stores, and dietary modification
222
patient presents with RUQ tenderness, elevated liver enzymes, and hyperinflated lungs
alpha 1 antitrypsin deficiency
223
dx for alpha 1 antirtyprsin (2)
blood test for levels and function of antitrypsin protein
liver biopsy
224
tx for alpha 1 antirtyprsin (1)
AAT replacement for lung injury. liver injury is non-reversible - eventually will need transplant
225
what BMI is morbid obesity
over 40
226
swollen smooth liver can be seen with (2)
edema
| fat
227
what test is less useful in people with morbid obesity
NAFLD fibrosis score calculator
228
where does collagen get laid down in fatty liver
perisinusoidal - in SPACE OF DISSE
229
where is scar in steatohepatitis and cirrhosis
steato = centrilobular
| cirrhosis - encircling hepatocytes
230
drinks/week risk factors for alcoholic liver disease
14/week for women
| 21/week for males
231
"metabolic syndrome" risk factors for non alcoholic fatty liver disease (5)
1. fasting glucose >100
2. obesity
3. triglycerids >150
4. BP over 130/85
5. HDL <40 in men and 50 in women
232
pathogenesis of non alcoholic fatty liver disease and steatohepatitis
in insulin resistance:
- decreased adiponectin (which, with the help of PPAR gamma, normally decreases lipid synthesis)
- triglycerides accumulate in liver
- SECOND HIT from microbiome - generates free radicals, stimulates inflammation
233
pioglitazone recommendation and adverse
recommeneded for NASH, but everyone gains weight on it
234
vitamin E adverse
in men is linked to prostate cancer
235
patient presents with jaundice, arthralgia, amenorrhea, fever for 4months. takes OCP. elevated liver enzymes, ANA and ASMA
Autoimmune hepatitis
236
what immune cell is predominant in the infiltrate in autoimmune hepatitis
T cells (also plamsa cells)
237
type 1 autoimmune hepatitis demographics and antibodies
(80% of AIH cases)
female, young
ANA and/or SMA
commonly associated with other autoimmune diseases (thyroid, UC)
238
type 2 AIH demographics and antibodies
anti LKM1 and/or anti LC1 or LKM3
mostly children
other immune diseases
progresssion to cirrhosis is common
239
which Ig levels are abnormal in AIH?
IgG is high
240
histo of AIH (2)
interface hepatitis (zone1 and triad)
plasma cells, lymphocytes
241
tx for AIH (3)
corticosteroids
azathioprine
6MP
242
phase 1 and 2 reaction enzymes and "zones" for drug metabolism
phase 1 cyt p450 (in zone3 - O2 depleted areas)
phase 2 glutathione (in zone1 - O2 rich areas)
243
R value
ratio of ALT/Alk phos:
greater than 5 = hepato
less than 2 = cholestasis
244
high INR means what
can't clot quickly enough
245
what kind of pathology does amox/calv cause
intrahepatic cholestasis
246
are NSAIDS predicatable or unpredictable
unpredictable
247
hepatic encephalopathy causes (4)
alteration of CNS due to hepatic insufficiency triggered by increased nitrogen, increased ammonia - encephalopathy
causes:
- infection
- upper GI bleed
- constipations
- electrolyte abnormalities
248
west-haven criteria/staging
for hepatic encephalopathy
stage 0-4:
- stage 0 have impoaried psychomotor testing
- stage 1 short attention, mild asterixis
- stage 2 - lethargic, asterixis
- stage 3 - will around
- stage 4 - comatose
249
how to dx hepatic encephalopathy
don't take ammonia level - might not represent brain levels
diagnosis of exclusion and clinical, eps with known cirrhosis
250
tx for hepatic encephalopathy (2)
1. lactulose - facilitates ammonia to ammonium, less absorbed
2. rifaximin - reduce bacterial production of ammonia
AVOID BENZOS
251
3 main mechanisms of ascites
1. portal htn
2. low albumin
3. peritoneal diseases - TB, cancer
252
serum ascietes albumin gradient (SAAG) - how do you get it, what is significant
subract ascitic fluid albumin from serum albumin:
normally less than 1.1
if more than 1.1 - 97% chance they have portal hypertension (albumin is large, can't cross barrier - stays high in serum)
253
if someone has ascites and is febrile, what are you thinking, and how can you tell if you're right
spontaneous bacterial peritonitis - do culture for PMN count>250
254
what causes spontaneous bacterial peritonitis
increased intestinal permeability, gut flora overgrowth - bacteria can translocate and colonize mesenteric lymph nodes and the fluid
255
tx for spontaneous bacterial peritonitis
life-long antibiotics
256
at what pressure gradient (between wedge hepatic and free hepatic venous) do you get worried at
10% - risk for variceal hemorrhage
257
red wale marking or white nipple sign - what is it, what does it indicate
red wale - vein very close to the surface,
| white nipple - fibrin clot on varices (in esophagus) makes you very worried about hemorrhages
258
what is primary preventative treamtnet for esophageal variceal hemmorage (BEFORE bleed) (2)
non selective beta blockers (propranolol, nadolol)
banding if BB not tolerated
259
what is acute management of variceal hemmorage (4)
1. volume, coag and hemodynamic stability recussitation
2. intubate
3. octreotide
4. antibiotics
260
if acute management of variceal hemmorhage does not work, what do you do next (2)
1. tamponade iwth balloon
| 2. TIPS (in portal system) shunt surgery
261
what does AFP (alpha fetal protein) elevation indicate (2)
chronic heptatitis (hep B with or without cirrhosis)
can indicate hepatocellular carcinoma when it's over 250
262
how do you dx hepatocellular carcinoma
triple phase CT (arterial phase, portal phase, venous phase - will see WASHED OUT venous phase
increased intesity during arterial phase
if no classic CT or lab values, then do biopsy
263
tx for HCC
liver transplant
(only a candidate if you have 1 tumor less than 5cm or less than 3 tumors less than 3cm)
local ablation, chemoembolization
264
surveillance for HCC
ultrasounds every 6 months for all patients with cirrhosis, or chronic hep B (africans younger, then asians, and family hx of HCC)
265
hepatorenal syndrome type 1
rapid decline in renal function (doubling of creat in less than 2 weeks)
266
hepatorenal syndrome type 2
less rapid - may be manged in outpatient
267
tx for hepatorenal syndrome
IV albumin, octreotide, midodrine
| only as bridge to liver transplant (necessary)
268
how do dx hepatorenal syndrome (3)
1. cirrhosis WITH ascites
2. serum creat >1.5
3. no response to volume expansion with albumin
269
non-specific stigmata of chronic liver disease 94)
1. palmar erythema
2. clubbing
3. spider angiomata
4. gynecomastia
increase in female estrogenic hormones and nitric oxide
270
portal hypertension cause classifications
prehepatic (portal vein thrombosis)
hepatic (cirrhosis, shistosoma)
posthepatic (budd-chiare, CHF)
271
what's a dangerous hepatic wedge pressure
over 12 - usually means cirrhosis
272
"compensatory" hypothesis for ascites
lymphatics weep, pressure pushes by hydrostatic pressure into peritoneal space, liver not making enough albumin, so not keeping osmotic pressure in vascualr space
273
"overflow" hypothesis for ascietes
primary renal retention - senses displacement of fluid into peritoneal space as hypovolemia - increases renin and aldosterone - sodium retention. makes more peritoneal fluid
274
what drugs do you stop if patient has ascites
NSAIDS and renal-toxic drugs like aminoglycodie antibiotics
275
tx for ascites (3)
diuretics: spironolactone and furosemide (watch for hypovolemic shock)
large volume pericentesis (not more than 4-5L)
with concurrent albumin infusion
276
when someone has really really bad breath, what do you think they might have, what substance makes the smell
hepatic encephalopathy , breath caused by mercaptor
277
child's pugh score
broad score of severit of cirrhosis using 5 parameters:
1. encephalopathey
2. ascites
3. high bilirubin
4. low albumin
5. decrased prothrombin ratio
```
A = normal paraeters (40mo)
B = 1-2 abnormal parameters (32mo)
C = more than 2 (8mo)
```
278
meld score critea
for transplant list
uses creatining, bilirubin and INR
less than 10 score (going to survive more than 1 year) not on list. has to have less than 1 year survival
279
liver neoplasms - benign (2) and malignant
benign
1- hemangioma (most common liver neoplasm) cavernous type can be problematic
2- hepatic adenoma - related to females because of estrogen, fibrous capsule with normal hepatocytes but no portal tracts or veins. can grow and rupture
malignant - HCC
280
what viruses ONLY cause acute hepatitis (7)
```
1- hep A
2- hep E
3- EBV
4- CMV
5- HSV
6- VZV
7- yellow fever
```
281
what viruses cause BOTH acute and chronic hepatitis (3)
hep B
hep C
hep D
282
average incubation for acute hep A
30 days - infectious 1-2 weeks before symptoms present
283
labs for symptomatic acute hep A and E (2)
ALT>AST, over 1,000
| elevated total bilirubin
284
types of hep E
5 types, 4 infect humans
GT1,2 have no animal reservoir and only fecal-oral transmission
GT3,4 is zoonotic - swine, deer, elk, bears, cattle (eating or bite from flea)
285
why do kids with Hep A or E have less severe symptoms than adults?
because the symptoms are a result of the immune response, not the virus itself
286
why is there a high mortality rate with hep E?
can get fulminant hepatitis if acquired during PREGNANCY (worse further along in pregnancy)
14-30% mortality rate in preg women
287
chronic hep E - what patients
transplant, chemo, HIV infected - rapid development of cirrhosis
288
definition of chronic viral hepatitis (timing)
hepatitis lasting longer than 3 months
289
hep B - when do infections occur
perinatal or early childhood
290
which of the hepatitis viruses are DNA
hep B
291
what antigens are specific for Hep B (3)
1. hep B surface antigen
2. hep B core antigen
3. hep B e antigen - marker of viral replication and infectivity
292
horizontal transmission of HBV (3)
1. needle sticks
2. sex
3. dialysis and transfusion
293
what can you do to reduce verticle transmission of Hep B?
give hep B immunogloblulin and vaccine to baby within 12 hours of birth
294
chronic hep B symptoms (4)
often nothing specific, but can have
1. cirrohsis symptoms
2. polyarteritis nodosa
3. glomerulonephritis
4. can go on to HCC because it integrates viral DNA (with or without cirrhosis)
295
HBV tx
tenofovir - nucleoside reverse transcriptase inhibitor - good because it's low resistance
296
hep D - who gets it
needs hep B for replication cycle
297
what causes symptoms of hep D
direct cytopathicity of virus - not from immune response like others
298
different classes of clinical preserntations of hep D (2)
can have coinfection:
- simultaneous hep B infection
- usually self-limiting
or
can have superinfection:
- acute D infection with chronic B infection
- get chronic D infection
- higher rates of liver failure, cirrhosis and cancer (worse than with B alone)
299
hep C viral characteristics (5)
1. flavivirus (like yellow fever)
2. infects only men and apes
3. very high replication rate
4. no proof-reading, so has high variablitly
5. uses membranous web for replication, does NOT integrate into DNA
300
what percentage of people with acute hepC progress to chronic
80-85%
301
what cofactors makes hepC infection worse and more likely to progress (4)
alcohol
HIV
male sex
older age
302
extra-hepatic manifestations of hep C (6)
1. cryoglobulinemia and assctd vasculitis
2. sjogren's
3. lymphoproliferative disorders
4. porphyria cutanea tarda
5. neuropathy
6. membranoproliferative glomeruloneprhtitis
303
fibroscan implication and use
for staging of liver disease
shear wave - faster it is the more scar you have
304
ribaviron mechanism of action
guanosine analog
inhibits viral RNA dependent polymerase, induces mutations in RNA
used for HCV
305
ribavirin adverse effect
hemolytic anemia
306
pegylated interferon mechanism of action
binds to membrane receptor and inhibits viral penetration, translation, transcription etc. ramps up immune system
(induces phagocytic activity of macrophages, prolieferation of cytotoxic T cells, and major histocompatibility complex antigens)
Hep C
307
pegylated intereron adverse effects
induces horrible flu-like symptoms
308
simeprevir mechanism of action
HCV protease inhibitor
used to treat HCV1
309
simeprevir adverse effects (3)
1- rash
2- photosensitiivity
3- drug-drug (p-glycoprotein transporter/cyp3A4 hinibitors)
(can have reactivation of HBV if co-infected)
310
sofosbuvir mechanism of action
RNA-dependent NS5B RNA polymerase inhibitor
has activity against all HCV genotypes and those resistant to PIs
311
sofosbuvir adverse effects (2)
1. not recommended for patients with severe renal dysfunction
2. drug-drug (P-gp induces like rifampin)
(can have reactivation of HBV if co-infected)
312
ledipasvir mechanism of action
inhibits NS5A protein which normally assembles the replisome
in combo with sofosbuvir = harvoni --> more effective
approved for HCV 1
313
ledpasvir adverse effects
no real toxicities by itself, but in combo with sofosbuvir can't take with renal dysfunction
(can have reactivation of HBV if co-infected)
314
benefits of most recent HCV txs (3)
approved for all genotypes of HCV
Zepatier can be used with renal impairment
cheaper
315
dx for acute hep A
IgM antibodies in first 3 months
316
what kind of bilirubin gets into urine to make it dark
conjugated
317
what's the cause of bruising in acute liver disease
decreased clotting factors
318
cause of small liver in acute case
hepatocyte drop out
319
how long does it take for albumin to get affected
20 days
320
viral has higher AST or ALT?
ALT (symptomatic 2-4 weeks post infection)
321
what zonality do you see in histo for acute viral hepatitis?
none - inflammation is througout
322
what zonality do you see in histo for chronic viral hepatitis?
zone 1 around portal tract
323
zonaity for balloon cells and mallory bodies
zone 3
324
what does pos AMA tell you
primary biliary sclerosis
325
what characteristic histo do you see for primary biliary sclerosis
florid duct lesion:
| granulomatous infiltrate around intrahepatic bile ducts
326
what liver lab test is high for primary biliary sclerosis
alk phos
327
really really high alpha fetal protein indicates what
cancer
328
long term, what is still present in someone who had hep B in the past, versus someone who was vaccinnated
past infection:
1. HepB surface antibody
2. HepB core antibody
vaccination
1. just HepB surface antibody
329
what lab values do you need for chronic hep B
have surface ANTIGEN, e antigen (can be pos or neg), IgG pos, and HBV DNA persists
CANNOT have sufrace antibody - that means you have immunity
330
what lab distinguishes chronic from acute hep B
acute has IgM and chronic has IgG
331
what weight/age is suspicious of poor growth
<5% on MORE THAN ONE occasion
332
what is hind milk and what is special about it
milk after feeding - higher proportion of fat - offer it in bottle after breastfeeding
333
how regularly should the baby feed
every 3 hours, for 20-30 minutes of active feeding
334
pyogenic liver abscess demographic and causes
middle-aged
- from biliary tree (cholangitis, stone)
- portal vein (diverticulitis, appendicitis, etc.)
- hepatic artery (endocarditis)
- penetrating trauma
335
deductive vs inductive vs abductiv reasoning
deductive (general hypothesis --> specific conclusion)
inductive (specific observations --> general conclusions)
abductive (incomplete observations --> likely explanation)
336
what causes narrowed pulse pressure (incr dec syst or dias)
increased diastolic
337
thromboelastograph (TEG) purpose
Tells about time, rate, quality of clotting
338
ATP and NADH and alcohol
ethoanol powers up ATP - increases ATP/ADP ratio and causes more reduced system (NADH/NAD ratio increases too)
favors SYNTHESIS and production of free radicals
339
how is ethanol produced in yeast
pyruvate --> acetaldehyde --> ethanol + co2 + NAD+
feedback inhibition --> why beer and wine have limited alcohol content
340
ehtanol metabolism in liver
alcohol --> (alcohol dehydrogenase) --> acetaldehyde --> (aledhyde dehydrogenase) --> acetate -->
341
MEOS system
electron transport system cyp2E1
alcohol --> acetaldehyde
produces FREE RADICALS
342
what percentage of alcohol goes through MEOS vs alcohol dehydrogenase system
20% through MEOS
80% through alcohol dehdyrogenase
alcohol dehydrogenase system maxes out at some point and then shunts to MEOS
343
what enzyme changes causes asian flush syndrome
increased ADH1 activity along with decreased ALDH2
344
which aldehyde dehydrogenase isoform localizes to mitochondria
ALDH2
345
which ADH has to do with retinol
ADH7
346
Which ADH has to do with alcohol metabolism
ADH1 dimers - alpha beta and gamma
347
which ADH isoforms has the highest/lowerst affinity for substrate
ADH1 beta1 - very low 0.05 - higher tolerance because alcohol doesn't build up
ADH1beta3 - very high 40 - alcohol builds up before it can be metabolized (seen more in native americans)
348
if you have a really active ADH and really inactive ALDH, what will happen
acetaldehyde is toxin and will build up if you consume alcohol
349
ecxess exposure to acetaldehyde can cause (3)
too much acetyl-CoA which makes KETONES andcan cause synthesis of triacylglyerols and cholesterol (FAT)
too much acetaldehyde causes FREE RADICALS
350
where is cyp2E1 found
inducible microsomal membrane based mini electron transport chain (MEOS)
converts alcohol to acetaldehyde and radicals
351
schiff bases and acetaldehyde
without NADPH alcetaldehyde reacts with lysine redicues to form unstable adduct of schiff base
352
VLDL in excess ehtanol systems
too much acetyl CoA buidlup and NADHPH/NADP ratio is high -- thus, under chronic conditions, VLDL isn't able to traffic all the fatty acids and trigclyerides outof liver -- causing accumulation and fibrotic lesions
353
gluconeogenesis, NADH and ethanol
excess NADH from ethanol metabolism drives pyruvate to lactate, all lactate (lactic acidosis) gets stuck in liver, blocks gluconeogenesis causing hypoglycermia
354
at what BAC does acetaldehyde dehydrogenase work and stop working
when BAC is less than 0.1% ADH works
above than, MEOS kicks in
355
disulfram mechanism
directly inhibits aldehyde dehydrogenase (ALDH) - accumulates acetaldehyde in system causing nausaea, vomitting, headache, and hypotension
356
what drugs have ethanol drug interactions that cause acetaldehyde accumulation (2)
metronidazole and some cephalosporins
hypoglycemics (sulfonylureas)
357
what are examples of p450 metabolized drugs that can have drug drug interactions with alcohol (5)
tricyclic antidepressnants
h1 antihistamines
OPIOIDS
BENZOs
358
whig drug drug interactions with chronic alcohol will cause induction of cyp2e1 and liver damage (1)
acetaminophen
give n-acetylcysteine
359
how many grams of ethanol is in a typical drink
15g
360
BAC calculation for one drink
15g in 50L (for a 150lb person) = 0.3 = 0.03%
361
how long does ADH metabolize asingle drink
1.5 - 2 hours
362
in non tolerant individual, what BAC can cause death (in absence of other drugs)
0.5% (BAC of greater than 500)
363
ethanol CNS effects (3)
enhance GABAa receptor (inhibitory neurotransmitter) - enhances receptor bidning, more negative membrane potential, less likely to fire --> CNS depression
also inhibit glutamate activation of NMDA - causing CNS depression
increases synaptic concentrations of dopamine and endogenous opiods in nucleus accumbens and ventral tegmental area -- leads to dependency and relapse
364
benzos and ethanol CNS effects
benzos and alcohol increase synergystic increased affinity for GABA and receptor causing increased CNS depression
365
two kinds of tolerance
1. MEOS enzyme induction
| 2. functional tolerance
366
3 ways that functional tolerance happens
reduction of CNS sensitivity to ethanol due to
- down reg of GABAa
- upreg of NMDA receptors
- up reg of voltage gated cA2+ channels
367
malabsorption of what vitamin causes unique syndrome in chronic alcoholics?
thiamine (B1)
368
Wernicke - Korakoff syndrome
associated with thiamin deficiency resulting in encephalopathy -- results from chronic alcoholism and malnutrition
presents with ataxia, confusion, memory loss, paralysis
369
where do lesions occur in wernicke-korsakoff
mammary bodies - repsonsible for spacial memory
370
teratogenic effects of alcohol
neurodegeneration and abberant neuronal and glial migration - sensitive in 1st and 3rd trimester
371
mild alcohol withrawl symptoms caused by what and treated by what (2)
caused by sympathetic nervous system, so can be treated by adrenergic drugs like CLONIDINE and peripherally acting PROPRANOLOL (non-selective)
372
Severe withdrawl symptoms caused by what, treated by what (2)
increased CNS excitation due to tolerance - neuradaptive changes are now upopposed - seizures
give tapered DIAZEPAM or other long acting BENZOs
373
how does disulfram work
purposefully inhibits acetaldehyde dehyrogenase - causing adverse reactions (nausaea, vomiting etc.) - associates alcohol consumption with adverse affects - behavior modification
374
Naltrexone mechanism
short circuit reward pathway
naltrexone - mu opionid receptor antagonist - binds in ventral tegmental, prevents beta endorphins from stimulating them, decreases craving in these individuals
375
what is reward pathway (3)
dopa neurons in VENTRAL TEGMENTAL area, send processes to
| acviate NUCLEUS ACCUMBENS which send processes to MEDIAL PREFRONTAL cortex (Reward cenral)
376
at what points in reward pathway does alcohol activate it
beta endorphis in ventral tegmental and dopamine in nucleus accumbens
377
what is neurochemical basis of replase
beta endorphins remain elevated in years, even in the absense of alcohol consumption - stimulate mu opioid receptors ventral tegmental area - lead to relapse
378
naltrexone adverse
1. hepatotoxic (contraindicated in liver failure or acute hepatitis) - disulfram also is, so don't give together
2. can cause severe withdrawal in opioid dependent individuals (give narcan challenge test - and give them disulfram, whic doesn't work on mu opioid receptor, or other anticraving)
379
anticraving drugs that you can give to opioid users (3)
1. acamprosate (anti-seizure drug) with increased effiacy in combo with disulfaram
2. topiramate (anti-seizure drug)
(don't treat the seizures from alcohol withdrawal with these, treat with long-active benzos)
3. SSRIs - anticraving esp in patients comorbid with major depression
380
moderate alcohol consumption and health
previous thought:
red wine has resveratrol antioxidant, decrease risk of MI
Lancet study (2018) proved that moderate alcohol consumption is NOT associated with benefit, in fact can decrease lifespan to up to 4 years
381
fomepizole mechanism
has high affinity for ADH - use in methanol and ethylene glycol poisoning (alternative to ethanol)
382
definition of chronic abdominal pain
2 or more months
383
functional abdominal pain - who gets it, what is it, characteristics
10-20% of children 4-6 and early teens
dysregulation of CNS and enteric nervous system
poorly localized, episodic, no red flags, may have other stressors
(biopsychosocial)
384
what 2 big things do you look at in CBC on kid with chronic abdominal pain
platelets
| hematocrit
385
if you think small bowel is inflamed in chronic abdominal pain, what do you look for on CMP (1)
albumin
386
calprotectin
breakdown products in colon -- indicates inflammatory bowel disease
387
TEF presentation
(1/3,000 most common congenital atresia)
USUALLY also presents with cardiac abnormalities
presents in the first few hours of life:
presents with vomitting, distension (swallowing air), regurg into airways
388
duodenal atresia radigraphic finding
"double bubble"
389
symptoms of duodenal atresia (3)
vomit - may be bilious or non bilious depending on the site of atresia
gasless abdomen - NO distension
burping and vomitting gas from stomach and duodenum
390
hypertrophic pyloric stenosis - when does it present
3-6 weeks of life
391
etiology of hypertrophic stensois (4)
acquired - genetic and environemntal
- prematurity
- bottlefeeding
- maternal smoking
- macrolide antibiotics
392
hypertrophic stensosi symptoms/findings (3)
1. hypochloremic, hypokalemic contraction alkalosis
2. projectile non bilious vomiting
3. palpable "olive"
393
non-pathologic infantile GER - when does it present, what does it NOT present with (3)
at 3-6 months, resolves by 18-24 months
DOES NOT present with barret's or aspiration or poor growth
394
is a PPI acid blocker going to reduce vomitting in kids
no
395
eosinophilic esophagitis symptoms across ages
symptoms can vary with the age:
infants = feeding problems, gagging, poor growth
school-age = volmitting, abdominal pain
adolescents = dysphagia, food impaction (due to strictures)
396
who gets eosinophilic esophagitis
more men than women
atopic individuals - allergies, asthma, eczema, family history
397
tx for eosinophilic asophagitis (2)
1. diet changes (get rid of dairy etc.)
2. swallowed steroids (swallow flovent) - not great for kids, stunts growth
3
398
functional constipation symptoms (3)
1. withholding - cross legs
2. encopresis - poop leaking (more severe behavioral component)
3. enuresis - pressure pushing on bladder - bedweting
399
peak age for IBD presentation
15-30
400
which IBD is more common in kids
crohn's colitis
401
2 unique complications in kids with IBD
growth failure
| pubertal delay
402
when do you want to do a bone scan
with crohn's
403
contrast for X rays (2)
iodine (vascular, oral, enema, cath)
barium (per oral, enema)
404
contrast for ultrasound
microbubbles
405
contrast for MRI
gadolinium
406
contrast for nuclear medicine
technicium 99m (radioactive isotopes)
407
ratio of radiation between a CT scan of abdomen to a chest xray
500:1
408
"string sign" on barium study - what does it indicate
indicates crohns
409
MR enterography - what do you see for crohn's
areas of hyperemia around a portion of intestine - shows active inflammation
410
air fluid levels in small bowel - what might that indicate
small bowel obstruction - small bowel loops have to also be dilated
411
what's the measurement for dilated appendix in appendicitis
more than 6mm, also see thick wall
412
radiographic alternatives to colonoscopy (2)
1. contrast barium enema
| 2. CT colonography (better for smaller polyps)
413
what radiolgraphic options are there to detect acute cholecystitis
1. US to see edema
| 2. 00mTc-IDA scan
414
when do you image acute pancreatitis
only if it's severe and has complications (hypotensive, drops pO2 etc.)
415
greater spanchnic nerve - what are its origins, and where synapse
from T5-T9
| pierces crux of diaphragm and synapses in the celiac ganglia and plexus
416
lesser spanchnic nerve - what are its origins, where does it synapse
from T10-T11
| synapses in SMA ganglia
417
least splanchnic nerve - what are its origins, and where does it synapse
from T12
| symapses on renal plexus and aorticorenal ganglion
418
lumbar splanchinic nerves from what origins and where does it synapse
from L1-L2,
| synapse in inferior mesenteric ganglion and superior hypogastric plexus
419
is thoracic and lumbar splanchnic sympathetic or parasymptatheic
sympathetic
420
what are the origins of the parasympathetic innervation to abdominal cavity (2)
vagus -- supplies foregut and midgut
sacral parasymathetics (From S2,3,4) -- supplies hindgut and pelvic organs (including descending, sigmoid, rectum and anus)
421
is pelvic splangchic sympathetic or parasymp?
parasympathetic
422
lymph draining from stomach gall bladder spleen
celica nodes
423
lymph draiing from midgut
SMA ndes
424
lymph draining from hindgut
iMA nodes
425
after celiac nodes, where does lymph drain to
cisterna chylii and thoracic duct
426
at what spine segment is rectosigmoidal junction
S3
427
how many transverse rectal folds are tehre
3
428
what is the muscle that keeps the anorectal flexure at 90 degrees
the puborectalis portion of the levator ani
429
what does superior rectal artery com from
IMA
430
what does middle rectal artery come from?
internal rectal artery
431
what does inferior rectal artery come from
internal pudendal artery
432
what is venous drainage of superior rectal vein
to inverior mesenteric to PORTAL system
433
what is venous drainage of middle rectal vein
to interla iliac vein to CAVAL system
434
what is venous drainage of inferior rectal vein
to internal pudendal vein to CAVAL system
435
superior half of rectum drains into what nodes
inferior mesenteric nodes
436
inferior half of rectum drains into what nodes
internal iliac nodes
437
what are anal columns made by
bulging of veins
438
what do anal valves and sinuses do
secrete mucus
439
below pectinate line nodal drainage
superfical inguinal nodes
440
internal hemorrhoids are dilations of what veins
superior rectal veins which drain to portal system
441
external hemorrhoids are dilations of what veins
inferior rectal veins which drain to caval system and are innervated somatically
442
portal hypertension can cause what heorrhoids
internal (portal system)
443
wha are the selective shunts
distal spleno-renal
| meso-caval
444
what does TIPS connect
inflow of portal vein and outflow of hepatic vein WITHIN liver
