GI Pathophysiology Flashcards
(95 cards)
1
Q
cranial nerve(s) for taste
A
back of tongue to front:
vagus (10)
glossopharyngeal (9)
facial (7) - chorda tympani
2
Q
physiological role of taste buds
A
tongue: tasting food
airways: glucose, bacterial signalling molecules for ciliary function and immune response
GI tract: sweet and bitter, vomit, ciliary, immune
3
Q
-guesia
A
taste problems
dysguesia - altered (such as more or less salty v sweet, which can lead to over-ingestion), medication effects (such as metallic or bitter taste)
hypo
aguesia - loss
can lead to undereating, eating spoiled foods
hyper
4
Q
saliva regulation
A
PNS (most)
- upregulated by food, smell, nausea
- down regulated by dehydration, fear, sleep
- ACh
- M3 (muscarinic) on acinar and ductal cells
SNS (some)
- leads to thicker saliva
- T1 to T3 nerve root
- norepinephrine
- beta-adrenergic on acinar and ductal cells
5
Q
xerostomia
A
dry mouth
d/t:
- meds
- Sjorgen’s, other AI
- radiation
- aging
c/q:
- low appetite, dysguesia
- impaired swallowing
- dental problems
- candidiasis
- glossodynia (tongue pain)
tx:
- switch or d/c offending meds if possible
- otherwise, pilocarpine (muscarinic agonist, stimulates saliva) ± salivary substitutes
6
Q
chewing regulation
A
trigeminal (5) nerve
initiation: voluntary
continuation: reflex
7
Q
swallowing regulation
A
brainstem
initiation: voluntary
continuation: reflex
8
Q
oropharyngeal dysphagia
A
difficulty swallowing
- poor bolus formation
- food retention in mouth
- possible aspiration
d/t:
- neuro
- LOC
- stroke
- brainstem lesion or mass
- myopathy/palsy
- throat problems
- oropharyngeal cancer
- scarring
- crichopharyngeal bar (hypertrophy)
9
Q
foregut, midgut, hindgut
A
embryological structures
foregut = upper part of GI tract and accessory organs
- esophagus
- stomach
- liver
- biliary system
- pancreas
- upper duodenum
midgut –> middle part of GI tract
- lower duodenum, jejunum and ileum (rest of SI)
- most of colon
hindgut –> lower
- distal colon
- andus
- rectum
10
Q
GI neurocrines
A
ACh
NE
VIP (vasoactive intestinal peptide)
enkephalins
11
Q
GI hormones
A
gastrin
CCK (cholecystokinin)
secretin
12
Q
GI paracrines
A
histamine
somatostatin
13
Q
Peyer’s patches
A
lamina of ilium
immune cells surrounded by single layer of epithelium
especially prominent in youths
- M cells function somewhat similarly to T cells, communicate with lumen antigens for specific response
- B cells, mostly IgA
14
Q
Location in brain and receptors responsible for nausea
A
Area postrema (in medulla) Serotonin/5HT3, histamine, dopamine
15
Q
Causes of nausea (general, not specific diseases)
A
Local factors
- GI Rhythm disturbance/spasm
- distention
- blockage
- chemical irritants
Central
- increased intracranial pressure
- psychological factors: stress, Pavlovian, smells, sights, thoughts, emotions
Circulating:
- drugs, toxins, meds
- uremia
- acidosis
- dehydration
16
Q
Location in brain responsible for vomiting
A
Central pattern receptor in NTS (nucleus tractus solitarus)
17
Q
Sequence of events vomiting
A
Autonomic discharge:
- increased HR
- sweating
- nausea
- salivation
Retching
- gastric slow wave abolished
- deep breath
- closed glottis
- ab and diaphragm contraction
- lower esophageal sphincter relaxation
Emesis
- ab and duodenal contractions
- increased intra-ab pressure
- retrograde contraction thorough upper esophageal sphincter
18
Q
esophageal mucosal tear
A
- occurs usually d/t prolonged forceful vomiting + esophageal insult such as food poisoning, alcohol
- initial emesis is non-bloody, then bloody
- usually not an enormous amount of blood but can be
19
Q
esophageal varices
A
- end stage process of portal hypertension (typically cirrhosis-related)
20
Q
ddx: forceful, non-bloody emesis followed by bloody emesis
A
- classic finding for esophageal mucosal tear
- consider other causes of bleeding such as peptic ulcer disease, esophageal varices, etc if suggested by hx
21
Q
when to start transfusion
A
\+ hemorrhage + hypovolemic shock Hgb 7 consider starting at higher Hgb if risk factors: -- active MI -- age -- pre-existing CV disease
generally restrictive about transfusion d/t risks, supply/demand
22
Q
labs to monitor when transfusing
A
** platelets - (1) with packed RBCs, you’re not transfusing platelets; (2) when they’re actively bleeding, they are losing platelets when they really need them
sodium - (1) whenever transfusing any fluids you’re messing with electrolytes; (2) they were probably hypER-Na to begin with and now you’re giving a bunch of things that are (somewhat) hypERosmotic
Hgb, CBCs - are you hitting goals?
iron (especially long term) - are you overloading?
23
Q
chron’s vs uc clinical features
A
Chron’s:
- anywhere in sb or colon
- patchy
- transmural
- granulomatous
- > 50% will require 1+ surgery
- surgery is risky
- pain ± diarrhea
- obstructive sx/constipation
UC:
- only in colon, always starting from rectum
- continuous
- mucosal
- non-granulomatous
- <50% require surgery, but surgery is curative
- pain only accompanying diarrhea
- diarrhea only, no constipation
both:
- 15-30 typical onset
- GI sx:
- diarrhea ± blood
- fecal urgency
- abdominal pain
- hyperactive bowel sounds
- perianal disease
- malnutrition sx
- weight loss
- anemia
- in kids: impaired growth, delayed puberty
- extraintestinal autoimmune sx
- fever
- tachycardia
- joint pain
- rashes
- possible complication: primary sclerosing cholangitis
24
Q
bowel/colon stricturing
A
stricture = very narrowed area
most common in Chron’s d/t inflammatory state
sx:
- cramping after meals
- hyperactive bowel sounds
- bowel obstruction
- vomiting
- food avoidance
25
severe forms of UC
(uc = ulcerative colitis)
fulminant colitis
toxic megacolon
can be cured by surgery
26
ibd labs and tests
labs:
* CRP for generalized inflammation
* Fecal calprotectin from stool sample for inflammation in colon
- CBC for anemia, leukocytosis
- albumin low in severe disease
- vitamin/nutrient/malnutrition panel
* colonoscopy
- - Chron's colitis / terminal ileitis
- - UC
small bowel imaging for Chron's
- - CT, MRI
- - capsule endoscopy
UGD for upper GI Chron's (less common)
27
tx severe ibd
surgery
hospitalization + strong immunosuppressants:
- cyclosporine
- anti-TNF (infliximab)
- IV steroids
28
tx moderate ibd
outpatient tx w/ immunosuppressants
- oral prednisone during *induction phase
- thiopurines, methotrexate, other immunomodulators during *maintenance phase
- biologics e.g. infliximab
general principle of achieving remission with induction agents (strong) and weaning to fewest drugs possible to maintain remission
29
tx mild ibd
outpatient tx w/
- elemental diet
- rectally administered steroids e.g. budesonide
- mesalamine, an NSAID specifically for ibd
30
histological signs of GERD
* 6+ layers of basal cells in epithelium (normal is ~4)
* extended vascular poles in epithelium
* eosinophils in epithelium
31
(possible) disease progression of GERD
GERD --> barret's esophagus --> esophageal cancer
32
layers of muscle throughout GI tract
2 in everything but stomach
- longitudinal + concentric = peristalsis
3 in stomach
- longitudinal + circular + oblique = churning
smooth muscle
33
tx bowel stenosis/strictures (a complication of IBD)
definitive: endo/coloscopic balloon dilation
ultra-definitive: surgical resection
m/w: npo, antiemetics, fluids, pain mgmt
± iv steroids
34
extraintestinal manifestations of IBD
ankylosing spondyliasis
SI joint dysfunction
rashes
others...
35
define zymogen
digestive enzyme released from pancreas
36
CCK produced by ___ and acts on ___
Secretin produced by ___ and acts on ___
Vagal ACh acts on ___
CCK produced by i cells and acts on acinar cells to produce zymogens
Secretin produced by S cells and acts on ductal cells to release Na+ and bicarb
Vagal ACh acts on both
some overlapping functions
37
cells of Cajal
colonic "pacemakers"
stimulate tonic contractions
determine speed of transit
38
diverticulosis vs diverticulitis
diverticulosis are outpouchings of mucosa and submucosa in the colon
common with aging (~60% by age 60)
usually asymptomatic
diverticulitis is inflammation or infection of these pouches and is a medical emergency
- usually (not always) treat with abx
- sometimes treat with surgery
- constant pain, usually LLQ
- ± constipation or diarrhea
- ± fever
- nonspecific labs
39
mutations in familial adenomatous polyposis (FAP)
APC
40
mutations in HNPCC
DNA mismatch repair genes
several possible specific mutations
(hereditary non-polyposis colon cancer)
41
hormone associated with carcinoid syndrome
serotonin/5-HT
metabolite 5-HIAA
this can be measured as a diagnostic
(this is a neuroendocrine colon cancer)
42
GIST
```
gastrointestinal stromal tumor
arises from cells of Cajal
most commonly in stomach
spindle-shaped
cKIT and DOG1+
tyrosine kinase KIT mutations
```
43
toxic megacolon
sequela of IBD, c. diff
gross dilation of large ± small intestine
treat underlying condition
44
toxic megacolon
sequela of IBD, c. diff
gross dilation of large ± small intestine
treat underlying condition
45
mechanism of pain in IBS
visceral hypersensitivity
| or undiagnosed
46
causes of cholelithiasis
- excess cholesterol in bile (by far the most common)
- -- mucin sludge + cholesterol microcrystals --> supersaturation
- -- impaired gallbladder motility
- -- lifestyle can help with prevention as it is linked to hypercholesterolemia, diabetes, and obesity; but there are also uncontrollable risk factors like F>M, genetics, Chron's, rapid weight loss, octrenide meds, fasting
- hemolysis= black pigment, radioopaque
- infection= brown pigment, radiolucent
47
hormone bile release
CCK
48
biliary atresia
- congenital or acquired biliary obstruction in newborns
- bilirubinemia, pale stool, jaundice
- a few weeks of life
- dx w/ cholangiogram
- requires surgery, good px after that
49
biliary colic
- uncomplicated biliary pain
- dull RUQ/EG discomfort. w/ sudden on-off starting an hour or so after fatty meal
- due to contraction against small stones
50
acute cholecystitis
- blockage of cystic duct by gallstone
- urgent to emergent surgery
- emergent IV fluids, pain control, abx (pip-tazo), admit
- possible perforation
- possible ileus (obstruction and fistula caused by large stone)
sx:
- RUQ/EG pain ± fever ± WBCs ± nausea and vomiting
- peritoneal signs and pain w/ movement
* Murphy's sign = pain w/ RUQ pressure + inhalation
- 4-6 hours, steady
dx:
- US
- ± cholescintigraphy/HIDA (dye) scan
- ± MRCP (magnetic resonance cholangiopancreatography)
51
Murphy's sign
acute cholecystitis
| pain w/ RUQ pressure + inhalation
52
choledocholecystitis
- obstructive jaundice (common bile duct obstruction)
- gallstone pancreatitis
- common with age
53
cholangitis
* high mortality
* most emergent
- biliary tract obstruction
- -> sepsis (often)
- infection-related: bacteria from gut via:
- - choledocholithiasis (CBD obstruction)
- - malignancy
- - stricture
- - post-surgery or ERCP (endoscopic retrograde cholangiopancreatography)
- - ulcerative colitis
tx:
- biliary drainage
- abx (pip-tazo)
- tx underlying condition
54
complications of primary sclerosing cholangitis
- sepsis
- high mortality
- cancer of gallbladder or bile duct
- cirrhosis r/q liver tpx
55
porcelain gallbladder
calcified wall d/t chronic inflammation
| multiple stones
56
sclerosing cholangitis
- progressive inflammation --> bile duct obliteration
- associated w/ IBD, UC>CD
sx:
- pruritus (usually first sx)
- jaundice
- RUQ pain
57
heme synthesis
TCA intermediate + one amino acid
early intermediates:
- delta-aminolevulinic acid (∂-ALA)
- porphobilinogen (PBG)
last step: chelation (Fe++)
-- inhibited by Pb++
negative feedback to ALA synthase
58
causes and effects of defective heme synthesis
cause:
- genetic
- Pb++ poisoning
effect:
- anemia
- etc
59
acute intermittent porphyria
- ∂-ALA and PBG accumulation d/t genetic defect
- visceral pain
- neurologic manifestations
60
porphyria cutenea tarda
- late-heme synthesis mutation resulting in buildup of porphyrins
- blistering cutaneous photosensitivity
61
Gilbert syndrome
- benign
- relatively low bilirubin-UGT levels
- buildup of conjugated bilirubin, low uncongugated bilirubin
- bilirubinemia
62
Crigler-Najjar syndrome
- more severe version of Gilbert syndrome
- absent or complete defect bilirubin-UGT
- buildup of conjugated bilirubin, no uncongugated bilirubin or bilirubin excretion
- hyperbilirubinemia
63
Dubin-Johnson syndrome and Rotor syndrome
buildup of conjugated bilirubin (unbound)
| defect in transporters
64
acute pancreatitis
- severe, persistent epigastric pain radiating to back + nausea and vomiting
- if mild, 3-5 day recovery (80% of cases)
- if severe (20%), systemic complications, organ failure, and possible death
exam:
- EG tenderness
- Cullen's sign = periumbilical bruising
- Grey Turner sign = flank bruising
- xanthomas (cholesterol-rich bumps on skin), if pancreatitis is caused by hypercholesterol
dx:
* lipase, amylase > 3x normal
- US to r/o other causes (e.g. biliary)
- triglycerides possibly >1000
- calcium
- hepatic panel
- CBC
causes:
- usually gallstones or alcohol
- also familial, autoimmune, infectious, spider and scorpion bites, idiopathic
65
Cullen's sign
periumbilical bruising
| acute pancreatitis
66
Grey Turner sign
flank bruising
| acute pancreatitis
67
pancreatic pseudocysts
- not "true" cyst d/t no epithelial lining, but significant buildup of serous fluid
- dx CT, US
- sx: pain, distension, anorexia, infection/abscess
68
chronic pancreatitis
- inflammation, scarring, fibrosis, eventual irreversible loss of function of pancreas
- moderate to severe chronic pain
sx:
- EG pain --> back
- after meal, lying down
- intermittent or constant
- steatorrhea (fatty stool) d/t (~90%) loss of exocrine function
- pain ≠ imaging severity
dx
* lipase and amylase either elevated or low d/t exhausted reserves
- tBili and alkaline phosphatase if bili is involved
- low vit D, other fat-soluble vitamins
- elevated tri >1000, intermittent or constant
- fecal elastase
- IgG4 if autoimmune
dx:
- pancreatic stim test
- imaging
causes:
- alcohol
- smoking
- hyper-triglycerides
- autoimmune
- obstruction
- hereditary
- idiopathic
complications:
- osteopenia
- type I-ish diabetes (LOF but not autoimmune)
tx:
* enzyme supplementation
* celiac plexus block for pain
69
ductal adenocarcinoma
- main pancreatic cancer
sx:
* low energy
* weight loss
* jaundice and hepatomegaly
- palpable RUQ mass
- anorexia
- cachexia
- abdominal pain
- dark urine
- Corvoisier's sign (tender, palpable gallbladder)
Rfx:
- smoking
- chronic pancreatitis
- diabetes
- age
dx:
- imaging
tx:
~ 15% surgical - Whipple
~ 60% metastasis - chemo
px:
- poor
- once metastasized usually <1 year despite chemo
70
aspartate aminotransferase
- AST
- released with hepatocyte, myocardial, or skeletal muscle damage
- part of liver function tests
71
alanine aminotransferase
- ALT
- most specific LFT for liver damage
- found in hepatocyte mitochondria
72
alkaline phosphatase
- ALP
- produced by bile duct, bone, placenta, intestinal damage
- part of LFTs
73
gamma glutamyltranspeptidase
- GGT
- hepatocytes and biliary tract
- nonspecific
- not in bone
74
LFTs
```
* ALT (liver, sp)
albumin
AST (liver, nsp)
ALP (bile, nsp)
* bilirubin (liver and bile, sp)
GGT (liver and bile, nsp)
prothrombin
INR
```
75
chronic liver disease vs acute sx
chronic
- may be asymptomatic
- fatigue
- malaise
- poor appetite
- itching
- weight loss
acute or end-stage
- jaundice and icterus (jaundice of eyes)
- dark urine
- abd pain
76
diagnosing and staging liver diseases
- biopsy, percutaneous or transjugular
- US
- MRI
- transient elastography: specialized US for fibrosis
early stages may be reversible
all paths lead to cirrhosis
77
liver failure sx
- small, nodular, cirrhosed liver
- jaundice, icterus, ^bili
- sex hormone dysfunction sx: testicular atrophy, gynecomastia, spider angioma, palmar erythema
- portal HTN: splenomegaly, ascites
- impaired detox --> neuro decline, asterixis (loss of motor control), and hepatic encephalopathy (swelling)
- esophageal and gastric varices as shown by EGD
78
liver failure lab findings
LOW:
- albumin
- thrombocytes
- clotting ability (i.e. increased INR)
HIGH:
- bilirubin
- INR
VARIABLE (dep on disease state):
- AST
- ALT
- ALP
- GGT
79
portal vein htn causes and effects
blood backs up into portal vein branches d/t
- cirrhosis*, sarcoidosis, schisto (intrahepatic)
- portal vein obstruction (prehepatic)
- hepatic vein obstruction, right HF, pericarditis (posthepatic)
branches:
- right and left gastric veins --> gastric and esophageal varices
- paraumbilical vein --> caput medusae (varices around umbilicus)
- splenic vein --> splenomegaly --> platelet consumption
- inferior mesenteric vein --> rectal anastomoses and varices
- superior mesenteric vein
other consequences:
- ascites from high intravascular pressure (blood backup) + low oncotic pressure (low albumin d/t liver disease) + Na+ and H2O retention d/t kidney effects
- -> liver disease
- intrahepatic = cause
- prehepatic = effect; insufficient blood supply to liver
- posthepatic = effect; intrahepatic htn
complications:
- spontaneous bacterial peritonitis = infection of ascites fluid typically d/t gut damage --> leakage of gut bacteria
80
spontaneous bacterial peritonitis
- infection of ascites fluid
- typically d/t gut damage --> leakage of gut bacteria; other sources of infection also possible
tx:
- usually single bacterial species
- start with 3rd gen ceph e.g. cephtriaxone, as this covers most of the common offenders
- abx prophylaxis can be used in high risk
sx:
- fever
- abd pain
- altered mental status
- neutrophilic ascites (> 250 PMN/mm3)
complications:
- hepatorenal syndrome (kidney failure w/ hypER-K, etc.)
81
tx cirrhotic portal htn
- tx underlying cause
- definitive: liver tpx
for ascites:
- diuretics e.g. furosemide and spironolactone
- salt restriction
- paracentesis (remove fluid via big needle)
for varices:
- non selective beta blockers e.g. propranolol to reduce pressure
- variceal ligation and obliteration
- TIPS (transjugular intrahepatic portosystemic shunt)
82
hepatic encephalopathy
- altered mental status d/t toxic buildup
- ranges from mild confusion to coma
dx:
- clinical presentation
- possible elevated ammonia (nsp.)
risk fc:
- infection
- constipation
- GI bleed
- renal failure
tx:
- underlying cause
- tx constipation: 3 soft stools/day w/ lactulose
- rifaximin $$ = chronic non-absorbable abx
83
end stage liver disease
decompensated cirrhosis:
- bleeding varices
- hepatic encephalopathy
- ascites
- jaundice
- LFTs very poor
dx:
- MELD score based on clinical criteria and labs (INR, bili, sCr)
tx:
- transplant: 1 yr survival = 92%, but few donors
84
acetaminophen-induced fulminant hepatic failure
~50% of all FHF
hyperacute: cerebral edema
subacute: renal failure, portal htn
(usually)
dx:
- clinical presentation
- hx of acetaminophen use
- - >12 g/24 h, 1-4 g per dose
- INR > 1.5 (slow clotting)
- elevated ALT/AST (>3500)
- low bilirubin
- no preexisting liver conditions
tx:
- NAC (n-acetyl cysteine) ~70% success
- rest need tpx ~70% success
- so overall ~90% survival
85
non-acetaminophen fulminant hepatic failure
d/t:
- viral hepatitis
- ischemic hepatitis
- Wilson's disease
- drug or supplement
- idiosyncratic
as with acetaminophen induced:
- INR > 1.5
- elevated ALT/AST >3500
- low bili
- no preexisting liver conditions
worse outlook than acetaminophen induced
~30% survival
86
alcoholic hepatitis
- hepatic steatosis (fatty liver)
- initially reversible
- if severe, poor short term mortality
- seen in 10-20% of alcoholics
dx:
- clinical
- AST/ALT > 1 (usually)
tx:
* prednisone
- supportive
- alcohol abstinence
87
hemochromatosis
- genetic: HFE gene
- high iron absorption w/o compensatory excretion
- -> oxidative stress, fibrosis
- sx don't usually develop until 40/60 y/o when iron has built up sufficiently
- can also be secondary to chronic transfusion
dx:
- high iron/transferrin
- high ferritin
- genetic testing
- biopsy
tx:
- serial phlebotomy
- iron chelation
88
Wilson's disease
- genetic: ATP7B copper transport gene
- copper gets stuck in hepatocyte (can't leave via transport gene)
- -> hepatocyte death and release of copper (so overall elevated Cu in liver, brain, cornea--ring around eyes, kidneys
- presents in teens/20s when copper has built up sufficiently and symptoms have progressed sufficiently
- sx usually subclinical prior to that
dx:
- ring around iris (Kayser-Fleischer rings)
- high urinary and serum copper
- low serum ceruloplasmin (copper-containing protein)
sx:
- neuro: movement disorders, dementia, psych sx
- Kayser-Fleischer rings
- hepatitis, acute or cirrhotic
- hemolytic anemia
- kidney disease
tx:
- chelation w/ *penicillamine
- liver tpx curative
89
alpha-1 antitrypsin deficiency
- genetic: infant, ped, and adult
- alpha-1AT buildup in hepatocytes
- fibrosis/cirrhosis
- high HCC risk
- requires tpx
- also lungs (panacinar emphysema, IPF w/o smoking hx)
90
primary biliary cholangitis (cirrhosis)
- T cell destruction of interlobular biliary epithelium
- -> cholestasis
- -> cirrhosis
- mostly middle-aged women
- often comorbid with other autoimmune
- especially UC>CD IBD
- environmental triggers such as infections and chemicals, including cosmetics
sx:
- fatigue
- pruritus
dx:
* anti-mitochondrial Ab
- ALP >1.5x normal
- ANA+
- hyperlipidemia
tx:
- ursodeoxycholic acid (slows)
- liver tpx
91
autoimmune hepatitis
- immune destruction of hepatocytes
- hepatocellular damage pattern
- -> cirrhosis
- mostly women, any age
- often comorbid with other autoimmune
- environmental triggers e.g. infections, chemicals incl cosmetics
dx:
- IgG elevated
* anti-smooth muscle Ab
* anti-liver-kidney microsomal Ab
- AST/ALT elevated
tx:
- prednisone
- other immunosuppressants
92
hepatic adenoma
- rare, benign liver tumor but carries bleeding risk
- F 30-50 d/t OCP hormone use
- resect if symptomatic
- otherwise just stop hormones
93
focal nodular hyperplasia
- common, benign, asymptomatic
- F 30-50
- "stellate scar" from abnormal blood vessel
- no intervention needed
94
hepatic hemangioma
- very common, benign
- usually asymptomatic, incidental finding on imaging
* don't biopsy as it is a vascular lesion
- F>M 30-50
- no intervention needed
95
hepatocellular carcinoma
- among most common causes of cancer death
- may be multiple synchronous tumors
sx:
- incidental from imaging
- abnormal LFTs
- weight loss
- anorexia
- jaundice
- decomp of stable cirrhosis
- new onset hepatic vein thrombosis (Budd Chiari syx)
causes:
- hep B
- cirrhosis
- afloxatin exposure
- at-risk should screen w/ US and serum alpha-fetoprotein (AFP) every 6 mo
tx:
- portal vein embolization
- transarterial chemoembolization
- radio frequency ablation
- surgery
- tpx if small lesions, not metastasized
