Block 3 (Lower GI) Flashcards
(95 cards)
1
Q
Structures that increase surface area in small intestine
A
Plicae circulares: permanent mucosal folds present in duodenum, jejunum, prox ileum (2-3x)
Villi: epithelium covered lamina propria, contain lacteals (lymph) and capillaries (10x)
Microvilli: extensions of apical plasma membrane (20x)
overall: 400-600x
2
Q
Epithelial cells of small intestine
A
Enterocytes: terminal digestion and absorption (300 microvilli/cell)
Goblet cells: secrete mucin, full of carbohydrate
DNES Enteroendocrine cells: secrete hormones
3
Q
Crypts of Lieberkuhn cells
A
DNES Enteroendocrine cells: secrete hormones, eosinophilic part faces outward
Stem cells: differentiate and divide, new cells progress outward to the tip of the villus then slough off (3-6 days)
Paneth cells: long lived, secrete lysozyme and defensins, eosinophilic part faces inward
4
Q
Different histological characteristics of the lower GI tract
A
Duodenum: Brunner's glands Ileum: Peyer's patches (GALT) Colon: just crypts, no plicae, no Paneth cells, lots of goblet cells Appendix: lots of lymphoid tissue Anus: squamous epithelium, glandular
5
Q
Mucin role in host defense
A
specific binding via adhesions of commensals
bacteria and LPS induce MUC gene expression
physical obstruction
contains IgA (serum=monomeric, mucosal=polymeric)
6
Q
Secreted chemical defenses in gut
A
acid RegIIIgamma lysozyme, MPO, SLPI Defensins, cathelicidins iron sequestration
7
Q
Antimicrobial peptides
A
defensins: cationic peptides
alpha- PMNs and Paneth cells, constitutive
beta- mucosal epithelium, can be inducible
8
Q
Microbial composition of lower GI
A
from proximal to distal: aerobic to facultative or obligate anaerobes
Infants: Bifidobacterium lungum
Functions: protective, structural, metabolic
9
Q
Microbiome assoc diseases
A
inflammatory bowel disease (IBD), Crohns esp: immune response to commensal
Obesity
Cancer
Allergy/asthma
10
Q
Uses of probiotic therapy
A
tx of IBS
milk allergy
atopic eczema
allergy
11
Q
Pancreatic secretions
A
Zymogens: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases
Enzymes: a-amylase, lipases, colipase, phospholipases, cholesterol esters, RNAase, DNAase
HCO3-
Controlled by: Ach, gastrin, CCK, secretin
12
Q
HCO3 secretion
A
pancreatic duct cells
stim by ACh and Secretin
13
Q
Digestion of fats
A
lipase (req bile salts and colipase) phospholipases cholesterol esterases Micelles Duodenum and jejunum Transport: chylomicrons and VLDL
14
Q
Digestion of proteins
A
Proteases: pepsinogen from stomach, trypsinogen (from a-cells of pancreas)- activated by epithelial enteropeptidase
trypsin activates chymotrypsin and elastase
Exopeptidases: carboxypeptidases (a-cells), aminopeptidases (intestinal epithelium)
absorbed by amino acid, di or tri peptide transporters in duodenum and jujenum
15
Q
Digestion of carbohydrates
A
a-amylase (saliva and pancreas)
di and trisaccharides (intestinal epithelial cells membranes in duodenum and jejunum
SGLT1 (glucose) and GLUT5 (fructose)
16
Q
Lastase deficiency
A
lastose intolerance
bloating and diarrhea from bacterial degradation of lactose
17
Q
Marasmus
A
severe reduction in caloric intake
depletion of somatic protein compartment
muscle loss
normal albumin
18
Q
Kwashiorkor
A
more severe than marasmus
protein deprivation is worse than caloric dep
or protein loss or malabsorption
loss of visceral protein store (spares muscle)
hypoalbuminemia
hypo/hyper-pigmented, fattly liver, immune def, anemia
19
Q
Fat soluble vitamins
A
A, D, E, K
20
Q
Water soluble vitamins
A
Non-B: C
B, energy releasing: thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), biotin (B7)
B, hematopoietic: Folate (B9), cobalamin (B12)
B, amino acid meta: B6 (pyridoxine)
21
Q
Vitamin absorption
A
most B-vit: duodenum and jejunum
B12: ileum
22
Q
Thiamine (B1)
A
cofactor for pyruvate dehydrogenase, cofactor in PPP
maintains neural membranes
Def is common in alcohlics
Dry beriberi- polyneuropathy
Wet beriberi- dilated cardiomyopathy
Wernicke-Korsakoff syndrome (Wernicke=reversible, nystagmus,, Korsakoff=chronic, irreversible, confabulation)
Tx: supplement, banana bag
23
Q
Pantothenic acid (B5)
A
coenzyme A
widespread in food
deficiency very rare
24
Q
Riboflavin (B2)
A
FMN and FAD
electron carrier
Def is rare except in alcoholics
Sx: cheilosis, angular stomatitis, glossitis, dermatitis
25
Niacin (B3)
NADH / NADPH
NADH: generated during degradation
NADPH: used in synthesis rxns
Def= Pellegra, uncommon except in alcoholics
Sx: dermatitis, diarrhea, dementia
Toxicity: flushing (levels used for hypercholesterolemia)
26
Biotin (B7)
carboxylase cofactor
synthesized by intestinal bacteria
Def= rare, can occur with raw egg whites
Biotinidase deficiency: can't convert dietary to free
Sx: neurological in infants, hair loss in adults (alopecia)
27
Pyridoxine (B6)
coenzyme for amino acid degradation, glycogen deg, porphyrin synthesis
Def: in alcoholics, kidney failure, isoniazid
Sx: cheilosis, angular stomatitis, glossitis, neuropathy, anemia (similar to thiamine)
Toxicity: peripheral sensory neuropathy
28
Folate (B9)
used in purine synthesis, dTMP synthesis, homocysteine to methionine
Sx: megaloblastic anemia, leukopenia, fetal neural tube defects (spina bifida occulta)
29
Cobalamin (B12)
absorbed with intrinsic factor in the ileum
stored in liver for 2yrs
methionine synthase, methyl malonyl CoA mutase
myelination
Sx: megaloblastic anemia, neural tube defects, dorsal and lateral tract demyelination
30
Ascorbate (vitC)
Antioxidant
cofactor for reducing metal ions
Def= scurvy (impaired collagen formation)
31
Tocopherol (vitE)
antioxidant
Def: uncommon
Use: prevent alzheimers
32
Phylloquinones (vitK)
```
cofactor for gamma-carboxylase
coagulation factors, bone Ca binding proteins
synthesized by bacteria in intestine
Def: rare (except w warfarin)
Sx: bleeding
```
33
Carotenes, Retinoids (vitA)
B-carotene: antioxidant
Retinol: transport form
11-cis Retinal: vision
Retinoic acid: gene regulation
Light converts 11-cis to 11-trans which activated G-protein, which activates a PDE, cleaves cGMP which closes an ion channel which sends signal to brain
Def: problem in developing nations
Sx: impaired vision, squamous metaplasia, urinary calculi
All but B-carotene are toxic at high levels
34
Calciferols (vitD)
controls gene expression
maintenence of normal calcium and phosphate levels
Def: children= rickets (bowed legs),, adults= osteomalcia (soft bendable bones, osteoporosis, dowager's hump)
Toxic at high levels
35
Zinc
component of enzymes, Zn fingers, spermatogenesis, skin maintenence
def: rare
Sx: rash, depressed wound healing and immune
Toxicity: inhibits copper abs
36
Iodine
component of thyroid hormones
def: rare
Sx: goiter, cretinism, myxedema
Toxicity: goiter, thyrotoxicosis
37
Copper
oxidation rxns, neurotransmitter regulation, CNS
Def: rare, Menkes syndrome
Sx: microcytic hypochromic anemia, neurological def, bleeding, neutropenia
Toxicity: Wilson's disease (neuro defects, Kaiser-Fleischer rings)
38
Selenium
```
component of glutathione peroxidase
antioxidant with vitE
regulate thyroid hormone
Def: myopathy
Toxicity: tooth decay and neuropathy
```
39
Waldeyer's ring
palatine tonsils, tubal tonsils, adenoid, lingual tonsils
Germinal center= B-cell
Parafollicular cortex= T-cell
unencapsulated
40
Lymph in GI mucosa
Lacteal - Lamina propria follicle (un-encapsulated)- mesenteric lymph node (encapsulated)
41
Ileal Peyer's Patches
follicle associated epithelium = M cells
basically a lymph node (un-encapsulated)
bacteria traffic through M cells to dendritic cells in Peyer's patch
42
Barrier between epithelial cells
in paracellular space: tight junction (claudin) and adherens junction (E-cadherin)
43
Immune response vs tolerance with intestinal dendritic cells
Immune response= IL-6 + TGFb = IFNg, IL17
| Tolerance= TGFb + RA = Treg cell
44
Immune cells trafficking to the gut
Gut homing: a4b7 integrin and CCR9
mucosal addressin: MadCAM on gut endothelial cells
Mucosal trafficking signal: CCL25
Dendritic cells produce retinoic acid
45
T-cells types and cytokines
```
Th1= IFNg (macrophage activation, IgG, intracellular microbes)
Th2= IL4, IL5, IL13 (IgE, parasites, allergies)
Th17= IL17 (recruit neutrophils, extracellular bacteria)
```
46
Infectious diarrhea
small bowel: watery, large volume, cramping, bloating, NO fever, NO blood or WBCs in stool
Large bowel: frequent small stools, painful BM or tenesmus, fever, bloody stool, RBCs and WBCs in stool
Causes: mostly viral (rotovirus, norwalk),, severe mostly bacterial,, small bowel can be protozoal too, or E histolytica in colon
47
Osmotic diarrhea
diarrhea equals body osmolarity = 290mosm/kg
cause: ingestion of poorly absorbed ions or sugars
Sx: disappears with fasting, low electrolyte concentrations in stool (large osmotic gap)
48
Secretory diarrhea
net secretion of anions or inhibition of sodium absorption
usually caused by infxn (enterotoxins)
Small osmotic gap
49
Osmotic gap
=serum osm - stool osm
stool osm= 2x(Na + K)
High in osmotic diarrhea (Mg ingestion)
Low in secretory diarrhea
50
Salmonella typhi
most common food borne disease in US
G- encapsulated bacilli
poultry, eggs, milk, pet turtles
colonic or dysenteric like illness, though is small bowel infxn
Salmonella osteomyelitis= sickle cell disease
51
Shigella
G- bacilli, unencapsulated, facultative anaerobes
highly contagious
daycare settings, kids, fecal-oral
Sx: self limited 6 days of diarrhea and fever,, often left colon
antibiotics help shorten
Rare: hemolytic uremic syndrome, reactive arthritis
52
Campylobacter jejuni
```
most common bacterial diarrhea worldwide
undercooked poultry, milk
incubation= 8days
influenza-like prodrome, self limited
watery or hemorrhagic
Sides: reactive arthritis, Guillain-Barre, pseudoappendicitis
```
53
Giardia lamblia
flagellated protozoan
drinking from mountain streams
acute or chronic diarrhea, bloating, small bowel dx
54
E coli
G- bacilli, commensal
Enterotoxigenic (ETEC): traveler's diarrhea, LT and ST toxins, increase intracellular cGMP (like cholera), Tx: fluoroquinolone or TMP-SMZ
Enteroinvasive (EIEC): bloody diarrhea
Enteroaggressive (EAEC): adherence fimbriae, damage is minimal
Enterohemorrhagic (EHEC): the bad one, undercooked beef, visibly bloody stool, NO fever, high WBCs, assoc with hemolytic uremic syndrome (worse with antibiotics)
55
Vibrio cholerae
G- bacteria
contaminated drinking water
noninvasive, produces enterotoxin, increases cAMP which opens CFTR, releases Cl into lumen (with water)
usually mild, but can be severe,, watery diarrhea
56
Norovirus
cruise ships, schools, etc
nausea, vomiting, diarrhea
self-limited
57
Rotavirus
```
most common childhood diarrhea
kids 6-24 months
day care
vomiting and watery diarrhea
vaccine now available
```
58
Ascaris lumbricoides
nematode, fecal-oral
| can cause ascaris pneumonitis
59
Strongyloides
parasite
fecal ground soil (can penetrate unbroken skin)
autoinfxn cycle, persistent
60
Necator americanus and Ancylostoma duodenale
hookworms, larva penetrates through skin
| leading cause of Fe def in developing world
61
Infectious diarrhea in immunocompromised
Parasites: cryptosporidium, etc
Bacteria: salmonella, campylobacter, shigella, MAC
Viral: CMV, HSV, adenovirus
62
Diarrhea timing after eating
within 6hrs= staph aureus (potato salad) or Bacillus cereus (chinese food)
8-14 hrs= Clostridium perfringens
more than 14hrs= anything
63
C. difficile
G+ spore forming anaerobe
risk: recent antibiotic use, hospital stay
fecal-oral, can be asymptomatic carrier (esp newborns)
Produces toxin A and B,, also is a hypervirulent strain: BI/NAP1/027
Sx: bloody watery diarrhea, fever, leukocytosis
Severe: toxic megacolon, sepsis, perforation
Tx: metronidazole, vancomycin if severe or recurrent
Also Nitazoxanide and Fidaxomicin maybe,, also probiotics and fecal transplants
64
Irritable Bowel Syndrome (IBS)
chronic and relapsing abd pain, bloating, diarrhea and/or constipation
poorly understood
females 20-40yo, developed countries
all normal findings, dx of exclusion
65
Diverticular disease
pseudodiverticular outpouchings of colonic mucosa (discontinuities in muscle wall)
becomes common 60+yo
high fiber diet helps
most common in sigmoid colon, can lead to diverticulitis or perforation
66
Ischemic colitis
mucosal infarction: hypoperfusion
Transmural infarction: arterial occlusion
most common in watershed zones: splenic flexure and sigmoid colon
Mucosa is hemorrhagic and ulcerated
self-limited once inciting resolved
usually older folks with vascular dx, sudden severe abd pain and bloody diarrhea
67
Celiac disease iceberg
Anyone with genetic susceptability (DQ2 or DQ8) is on the berg
healthy (non-celiac) is IgA EMA negative
for IgA positives: can be silent, but with some intestinal mucosal abnormality
Can be "atypical" or can be classic
Classic= diarrhea, bloating, abd pain, weight loss
Atypical= Fe/Folate/B12 def, osteoporosis, dermititis herpetiformis, IBS, DM1, elevated LFTs, amenorrhea, infertility
68
Celiac disease
common in N european descent
genetic risk: HLA class II DQ2 or DQ8
assoc with other autoimmunes, Downs and Turner
Also can have selective IgA deficiency
Dermatitis herpetiformis: extensor surface of extremities, very indicative of CD
Have autoantibody (IgA usually) against deaminated gliadin
Test: IgA tissue transglutaminase (tTG). also IgA level
Small intestine biopsy: scalloping or notching of folds, villous atrophy, lymphocytosis, crypt hyperplasia
Tx: gluten free diet
Sides: increase in all cause mortality, enteropathy assoc T-cell lymphoma, malabsorption
69
Wheat allergy
IgE mediated classic food allergy
have normal allergic reaction signs
normal antibodies, normal intestines
can be confused with celiac
70
Non-celiac gluten sensitivity
maybe real, maybe not
seems likely that gluten free diet may help some people
many reasons for this potentially
71
Environmental Enteropathy (Tropical sprue)
syndrome of stunted growth and diarrhea common in developing countries
repeated bouts of diarrhea in first 3 years of life
histologically similar to celiac
malnutrition may play a role, also some infectious bugs
72
Malrotation
bilious emesis after first feeding in newborn
surgical emergency
winds around narrow mesenteric base
Also Ladd bands can obstruct duodenum
Dx: no air in GI tract, do upper GI contrast
Tx: Ladd's procedure (surgery untwist bowel, appendectomy, SB on right, colon on left)
73
Duodenal atresia
prenatal ultrasound with "double bubble", also polyhydramnios
failure of recanalization
clear or bilious vomit w/in hours of birth
Assoc: Downs, other congenital abnormalities
Tx: NG tube, duodenoduodenostomy
74
Jejunoileal atresia
bilious emesis
in-utero vascular disruption- ischemic necrosis- necrotic tissue reabsorbed, leaves blind ends
Assoc with inherited thrombophilia or maternal use of vasoconstrictors
NOT usually assoc with other abnormalities
Tx: surgery
75
Hirschsprung's Disease
aganglionic bowel, defect in migration of neural crest cells - functional obstruction, usually in rectosigmoid
fails to pass meconium, bilious emesis, possibly enterocolitis
dx: suction rectal biopsy- no ganglion cells
more in males, assoc with Downs and RET mutations
Tx: surgical resection
76
Necrotizing enterocolitis
most common in premature infants
breast milk and probiotics are protective
Dx: abd distention, abd wall erythema, pneumatosis (gas within bowel wall from bacteria within mucosal layers)
Tx: antibiotics, NPO, TPN, surgery if free air
77
Anorectal malformations
usually full term birth, no polyhydramnios
Assoc with Downs and VACTERL
abnormality of caudal descent of urorectum
Males: usually high, rectum to bladder fistula
Females: usually low, rectum to perineum or vestibule
Tx: colostomy with later pullthrough surgery
78
Small intestine neoplastic disorders
only 3-6% of GI tumors
usually adenoma (near ampulla)
can also be carcinoid or adenocarcinoma
or GIST, lipoma, lymphoma
79
Small intestine adenocarcinoma
risks: crohn's dx, celiac dx, familial polyposis syndrome
80
GIST small intestine tumor
mesenchymal origin, from Cajal cells
seen with: carney triad, neurofibromatosis, Carney-Stratakis syndrome
GI stromal GIST= c-kit mutation, also DOG1, CD34+, sometimes PDGFRA
81
Carcinoid tumor of intestine
neuroendocrine tumor, secrete bioactive componds
| elevated serotonin
82
Hamartoma Polyps
benign tumor
mature, histologically normal cells
due to developmental error
Juvenile polyps: kids, pedunculated large, cystic dilated tortuous glands with inflammation
Juvenile polyposis syndrome: SMAD4, BMPR1A, increased risk of colon cancer
Peutz-Jeghers syndrome: STK11, large pedunculated polyps, hyperpigmentation, increased risk of cancer
Cowden syndrome: PTEN mutation, assoc with thyroid and breast CA
Cronkhite-Canada: rare, ectodermal abnormalities
83
Other non-neoplastic polyps
inflammatory: pseudopolyps (IBD)
Lymphoid: normal
84
Serrated polyps
usually in rectosigmoid
serrated lumina, goblet cells, small
Most: hyperplastic, no malignant potential, distal
Some: sessile serrated, proximal, high malignant potential, BRAF V600E mutation
85
Adenomatous polyps (adenomas)
```
epithelial proliferative dysplasia
precursor to adenocarcinoma
Tubular, villous or tubulovillous
Common after 60yo
Tubular: small pedunculated
Villous: large, sessile, more invasive
```
86
Colorectal adenocarcinoma
usually in rectosigmoid
Dx: Fe def anemia, napkin-ring constrictions
Inactivated APC gene- B-catenin mutation- WNT signalling- loss of p53 late
TNM staging
EGFR is a key target for some tumors (not effective if KRAS or BRAF mutation)
87
Familial adenomatous Polyposis (FAP)
```
auto dominant
bunches of colonic adenomas
germline mutation in APC
increased risk of adenocarcinoma
Tx: prophylactic colectomy
```
88
FAP variants
Gardner's syndrome: + asteomas, epidermoid cysts, desmoid tumors
Turcot syndrome: + medulloblastoma
89
MYH Associated Polyposis (MAP)
similar phenotype to attenuated FAP, usually only 20-100 polyps
auto recessive
due to mutation in MYH gene- DNA repair protein
90
Lynch Syndrome (HNPCC)
Increased risk of adenomas and carcinomas
genetic defect in DNA mismatch repair genes (microsatellite instability pathway): MLH1-MSH2, PMS2-MSH6
When staining for above proteins, if MLH1 and PMS2 are missing, then may be LS or sporadic,, if PMS2, MSH2 or MSH6 are missing, then LS
usually tumors are mucinous, infiltrative lymphocytes, and crohn rxn
NEVER has BRAF mutation
Muir-Torre syndrome: sebaceous -omas and keratoacanthomas
91
Tumors of the appendix
most common= carcinoid
mucocele= not really a tumor
Mucinous cystadenoma= mucous secreting epithelial tumor
92
IBD: Ulcerative Colitis (UC)
continuous inflammation starting from rectum
Colon ONLY
superficial (mucosal) inflammation
increased risk of GI cancer
Smoking is protective, risks: white women
Sx: diarrhea, bloody with mucus, abd pain, fever, urgency
Endoscope: erythema, edema, pseudopolyps, ulcers
Fulminant Colitis= severe UC + fever, elevated WBCs, unstable vitals
Complications: episcleritis, uveitis, Toxic megacolon, perforation
93
IBD: Crohn's Disease (CD)
patchy inflammation all over GI, mostly in cecum
full-thickness inflammation, thickened wall
cobblestone appearance
risks: smoking, females, whites
Sx: abd pain, diarrhea, fevers
Endoscope: aphthous ulcers, cobblestoning, discontinuous "skip" lesions
fistulas and strictures, granulomas, risk of cancer
Complications: erythema nodosum, pyoderma gangrenosum
Genetic: NOD2 mutation
94
Treatment for IBD (UC and CD)
nowadays: biologics (anti-TNF)- infliximab
| minimize steroids
95
Microscopic Colitis
Chronic nonbloody watery diarrhea w/out weight loss
Collagenous colitis: dense subepithelial collagen layer, increased lymphocytes
Lymphocytic colitis: collagen layer is normal, more lymphocytes
