1. Northside Medical Center
October 31st, 2013
Gagandeep Singh Anand (ganand@uwaterloo.ca)

2.  Patient Name: Ms. J. P.
 Age: 77
 Sex: Female
 Ethnicity: Caucasian
2

3.  “Persistent diarrhea and pruned skin”
3

4.  Ms. J is a pleasant 77 year-old female who presents
with persistent diarrhea for 3 weeks, at 4-5
times/day. It is of watery consistency, brown color,
foul smell, with traces of blood – though the patient
reports of internal hemorrhoids as a possible reason
– no mucus, and of undigested food.
 The patient reports increased urge to void after
consuming a meal and a coinciding BM with
micturition, in addition, she reports of a
progressively worsening frequency. She does not
report of any active pain, but of slight lower
abdominal discomfort for 15-20mins after a BM.
4

5.  Ms. J reports of having a previous episode (2010) with similar
symptoms which was diagnosed as pseudomembranous colitis;
she reports of no nausea, vomiting, sick contact or recent
travel. Ms. J also reports of acute stress due to a sickness in
the family.
 She was prescribed Flagyl (metronidazole) for 10 days, for
which she is on her 10th day. She was advised by her PCP to
consume bananas and cheese to help with the diarrhea but
had no improvement.
 Ms. J reports having a dental procedure one month ago in
which amoxicillin (4 tabs) was used.
 She also stopped taking her monthly Simponi (Golimumab)
injections for her RA because she believed it was the cause.
5

6.  Pseudomembranous colitis (2010)
 Fibromyalgia for 25+ years
 Rheumatoid arthritis (Type III hypersensitivity,
anti-CCP+, HLA-DR4)
 Psoriatic arthritis (RA affecting fingers and toes,
HLA-B27)
 HTN
 Internal hemorrhoids
 COPD (↓ FEV1/FVC ratio)
6

7.  Laproscopic Cholecystectomy
 Dilation and curettage
 Joint surgery of left shoulder / knees BL / hips BL
for RA
 Intraocular lens (IOL) implants for cataracts in eyes
BL (1993)
7

8.  Her mother (at 93) & father (at 83) both died of
strokes.
 Her son (57) recently had a stroke (July) and has a
pacemaker.
 She has an older sister (86) who had uterine cancer.
 She also mentioned Irritable Bowel Syndrome
present in the family.
8

9.  Divorced, lives by herself in an apartment building
and is “quite active”.
 Drives and attends bible meetings on a weekly
basis.
 No 1st hand smoking – only history of extensive 2nd
hand smoke through family.
 No alcohol.
 No illicit drugs.
9

10. Medications
 Diovan (valsartan) – 160mg daily
 AT II inhibitor
 Protonix (pantoprazole) – 40mg daily
R/O
 inhibit H+/K+ ATPase in parietal cells
 Simponi (golimumab) – 2 IM per
month
 monoclonal Ab for TNFα
 Heparin – tid
 activates antithrombin, ↓ thrombin & ↓
Xa
Allergies
 Latex
10

11.  General: Denies fever, chills, sweats
 HEENT: Occ. forehead aches, h/o head trauma on ice (4-5 yrs ago);
denies visual changes or pain; had ear wax removed, denies hearing
loss / tinnitus / vertigo / ear pain / discharge; reports some nasal drip,
sinusitis; denies teeth problems / abnormal taste / sore throat / speech
difficulty
 Cardiopulmonary: Denies cough / dyspnea / wheezing / hemoptysis /
chestpain / palpitations / orthopnea / PND / syncope
 Gastrointestinal: Normal appetite, persistent diarrhea (4x/d), lower
abdominal pain after BM (for 15-20min), h/o internal hemorrhoids
 Genitourinary: Denies dysuria / discharge / nocturia. Watery BM
coincides with micturition.
11

12.  Musculoskeletal: h/o RA, stiffness of left shoulder, denies stiffness of
knees or hips.
 Dermatological: Reports chancre sore on top lip after dental
appointment (< 1 mo ago) – antiviral was prescribed. Reports prior
pruning of skin, denies pruritus / rash / changes in hair
 Neurological: Some moving pain, “maybe associated with the
fibromyalgia”, denies seizures / paralysis / muscle weakness /
cognitive complaints
 Psychiatric: Some acute stress due to a family sickness (son had a
stroke 1 month ago and is unable to work). Denies suffering from
depression or anxiety other then that.
 Endocrine: No history of thyroid problems or DM.
 Hematology: Denies bleeding or clotting / easy bruising
12

13.  BP sitting: 114 / 70
 Pulse Rate: 65
 Pulse Rhythm: Regular
 Respirations: 16
 Temp: 98.0 °F
 Height: 62”
 Weight: 140 lbs
 Pain: no acute active pain
13

14.  General: AAOx3, very pleasant, NAD
 HEENT: NC, AT; PERRLA, EOMI; hearing grossly intact, ø
ear inflammation / discharge; patent nares, ø discharge /
inflammation; ø gland enlargement / erythema / exudates
 Mouth: Lips dry, mucosa moist, ø angular cheilitis, dentition
intact and normal, ø mucosal / tongue lesions
 Neck: supple, ø JVD / lymphadenopathy, trachea midline
 Chest Wall: Symmetrical bilaterally, ø tenderness upon
palpation
 Breasts: Not performed
14

15.  Lungs: CTA B/L, ø rhonchi / wheezing
 Heart: S1/S2 +, RRR, murmur -
 Abdomen: LLQ surgical scar, soft, NT, ND, BS + (in 4
quadrants), ø organomegaly, ø pain to superficial/deep
palpation
 Genitourinary: Not performed
 Musculoskeletal: 3/5 ROM on left shoulder, ø acute pain, ø
edema / clubbing / cyanosis. Radial pulse full and equal
 Neurologic: CN 2-12 grossly intact
 Skin: Warm & moist, ø gross lesions
 Psychiatric: Patient’s affect is congruent with mood
15

16.  WBC: 4.5  5.5 x 103 per μL
 Hb: 10.8  12.1 g/dL
 Hct: 33.2%
 PLTs: 159 x 103 per μL
 Na+: 141 mEq/L
 K+: 4.2  2.8 mEq/L
 Cl-: 108 mEq/L
 HCO3
-: 27 mEq/L
 BUN: 10 mg/dL
 CR: 0.7 mg/dL
 Glucose: 96 mg/dL
 Lactic acid: 2.3  1.7 mEq/L
 Ca2+: 8.2 mg/dL
 Phosphate: 1.9 mg/dL
 Amylase: 16 U/L
 Lipase: 59 U/L
 Alk. Phos.: 60 U/L
 Albumin: 3.6 g/dL
 ALT: 40 U/L
 AST: 36 U/L
 Bilirubin: 0.8 mg/dL
 Mg+: 1.7 mEq/L
 C. difficile Cx: Negative
 Urine Analysis:
 Leukocyte Esterase: Positive (25)
 WBC: Positive (5-10)
 Bacteria: Moderate 16

17. 1.Persistent diarrhea: complete Flagyl dosage, re-
send stool for WBC, Cx, ova & parasites.
Continue 100 cc/hr IVFs to rehydrate and replenish
electrolytes.
Consider vancomycin. Consider endoscopy.
2.Lactic Acid Elevation: 1.7  2.3 mEq/L.
Continue IVF’s.
3.Asymptomatic Bacteriuria: elevated LE, WBC &
moderate bacteria. Denied urinary Sx on admission.
4.H/o Psoriatic arthritis: continue to see
rheumatologist on OP basis, presently no
medications. 17

18. 5.H/o Fibromyalgia: no acute issues
6.H/o RA: consider holding Simponi injections if RA
asymptomatic. Consult with specialist.
7.HTN: continue valsartan 160mg daily
8.H/o COPD: no acute issues
9.DVT prophylaxis: heparin tid
18

19.  Pseudomembranous colitis (C. difficile) 2o to antibiotic use
 Gram-positive obligate rod. Toxins bind brush border, destroy
cytoskeletal structure of enterocytes. 2o to clindamycin/ampicillin.
 Watery diarrhea, abdominal pain, anorexia, malaise, fever.
 Irritable Bowel Syndrome
 Recurrent abdominal pain with 2 or more: pain improves with
defecation, changing stool frequency, changing stool appearance.
 Middle-aged women, chronic, may have diarrhea/constipation.
 Inflammatory Bowel Disease
 Crohn’s disease: rectal sparing, transmural, “string sign” on Ba swallow,
Th1 mediated.
 Ulcerative colitis: continuous until rectal, bloody diarrhea, “lead pipe”
appearance on imagining, Th2 mediated.
19

20.  Infections (watery diarrhea):
 Vibrio cholera: ↑ cAMP, Gs
 C. perfringens: gas gangrene, lecithinase α toxin
 Protozoa: Giardia (foul-smelling, campers/hikers, fatty diarrhea,
trophozoites/cysts in stool), Cryptosporidium (AIDS pts)
 Strongyloids stercoralis: larvae in soil penetrate through skin
 Enterotoxigenic E.coli: traveler’s diarrhea, ST & LT toxins
 Viruses: Rotavirus (dsRNA), norovirus (ssRNA)
 Endocrine disorders:
 hyperthyroidism, diabetic gastroparesis, niacin deficiency
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21.  Malabsorption syndromes:
 Whipple’s: Tropheryma whipplei (gram+), PAS+, foamy macrophages,
[CVS, arthralgias, neuro.] symptoms, older men.
 Celiac spruce (autoantibodies to gluten): distal duodemum, proximal
jejunum, loss of villi.
 Disaccharidase deficiency (lactase): normal villi, lactase located at tips of
villi, can occur following injury (e.g., viral diarrhea).
 Pancreatic insufficiency: cystic fibrosis, cancer, chronic pancreatitis, ↑ fat
in stool.
21

22.  Bacterial flora of colon disturbed C. difficile colonize  toxins
released  mucosal inflammation and damage
 Antibiotics: ampicillin/amoxicillin, clindamycin, cephalosporins (esp. 2nd &
3rd gen.), and fluoroquinolones
 ToxA (enterotoxin) or ToxB (cytotoxin) bind cell surface receptor
 endocytosis of toxin-receptor complex
 low endosome pH leads to pore-formation
 glucosyltransferase (GTF) & protease translocation into cytosol
 cysteine protease domain activated by inositol
hexakisphosphate (InsP6) cofactor, cleaves toxin, releases GTF
domain into cytosol
 RHO-family gets glycosylated  RHO GTPase inactivated
 RHO proteins: assist in actin polymerization, cytoskeletal
architecture, and cell movement  Inflammation & damage
22

23. 1. Domain B (green): carboxy-
terminal 'binding' domain binds to
a cell surface receptor
2. Domain D (yellow): the 'delivery‘
domain is involved in translocation
of the toxin into the cytosol
3. Domain C (blue): cysteine protease
'cutting' domain
4. Domain A (red): biologically active
glucosyltransferase domain
23

24.  Leukocytosis (15,000 μL)
 Acute kidney injury: Elevated WBC and Creatinine (1.5x pre-
morbid level)
 Electrolyte imbalances, dehydration, hypoalbuminemia, anasarca
 Stool Examination & Stool Assay’s:
1. Culture (gold-standard)
2. Glutamate dehydrogenase (GDH) enzyme immunoassay (EIA)
3. Real-time PCR gene toxin
4. Cell cytotoxic assay
5. EIA for ToxA and ToxB
6. Latex agglutination to detect GDH
Guidelines suggest: # 2 (detection) & # 4 (confirmation)
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25.  Endoscopy: raised, yellowish white, 2- to 10-mm plaques
overlying an erythematous, edematous mucosa
 Histologic: biopsy reveals an inflammatory exudate composed
of mucinous debris, fibrin, necrotic epithelial cells and
polymorphonuclear cells
25

26.  Computed Tomography Scanning: Marked colonic wall
thickening. Ascites, irregularity of bowel wall, pericolonic
stranding, megacolon.
26

27.  Pharmacological:
 Mild-Moderate: metronidazole / vancomycin PO (10-14 d)
 Severe-complicated: empirical vancomycin PO (10-14 d)
 Relapse from mild-moderate:
 1st relapse: metronidazole (forms free radical metabolites in bacteria)
 2nd relapse: vancomycin (binds D-ala D-ala of cell wall precursors)
 Probiotics may be useful for prevention
 Fecal Microbiota Transplanation: transfer healthy donor stool
to C. difficile infected patient
 reconstituting normal colonic flora
 Very promising results!
 Surgical: fulminant colitis & toxic megacolon require surgical
intervention
27

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29. 1. http://radiographics.rsna.org/content/20/2/399/F39.expansion.html
2. http://www.uptodate.com/contents/chronic-diarrhea-in-adults-beyond-
the-basics
3. http://emedicine.medscape.com/article/186458-overview#aw2aab6b2b2
4. http://www.nature.com/nrmicro/journal/v9/n7/box/nrmicro2592_BX1.ht
ml
5. http://emedicine.medscape.com/article/186458-workup#a0756
6. http://emedicine.medscape.com/article/186458-workup#aw2aab6b5b3
7. http://eguideline.guidelinecentral.com/i/53988#
8. http://us.123rf.com/400wm/400/400/mscates/mscates1201/mscates1201
00011/11870590-a-doctor-with-a-thumbs-up-sign-isolated-on-white.jpg
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