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Author(s): Rebecca W. Van Dyke, M.D., 2012

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M2 GI Sequence

          A GI Smorgasbord:
         Common GI Problems

              Rebecca W. Van Dyke, MD




Winter 2012
Industry Relationship
         Disclosures
 Industry Supported Research and
       Outside Relationships

• None
Topics

• Bright red blood per rectum

• Iron deficiency anemia

• Patient presentation: IBD and disease/surgical
  issues from a patient perspective
Bright Red Blood Per Rectum


  A common problem seen in most
        areas of medicine
Bright Red Blood Per Rectum
• Passage of small amounts of BRBPR is
  common
  – Affects at least 20% of general public at one
    time or another
  – Usually trivial, but can reflect serious disease


• BRBPR – location
  – On toilet paper
  – Streaks on stool
  – Dripping into toilet bowl
  – On underwear
Bright Red Blood Per Rectum
• Differential diagnosis:
  – think types of diseases that could cause small
    amounts of bleeding
  – usually in distal colon or anorectal area:
     •   Trauma
     •   Neoplasia
     •   Infection/inflammatory
     •   Vascular
Bright Red Blood Per Rectum
• Diagnoses after full investigation:
   – 20+%:       Nothing found – presumably tissue tears had
                     healed at the time of investigation
   – 50+%:       Anorectal disease
                     Hemorrhoids
                     Anal fissures
                     Trauma with tissue tears (ask patient )
   –   20-40%:   Polyps (hyperplastic/adenomatous)
   –   2-7%:     Colon cancer (increase with age)
   –   5-15%:    Inflammatory bowel disease
   –   2-5%:     Vascular lesions
                     arteriovascular malformations (AVMs)
   – 1%:         Benign ulcers
                     NSAIDS, stercoral related to chronic constipation
Bright Red Blood Per Rectum
• Goal: Find a disease you would treat
• Evaluation – little evidence to guide you
  – Can do full colonoscopy in everyone

  – Alternative: no clues to disease, no family history of
    CRC:
     • <40, reassure or just do flex sig and Rx constipation
     • 40-49: flex sig or colonoscopy
     • >50: full colonoscopy

  – If disease clues (diarrhea, frequent/continued bleeding,
    iron deficiency, pain) or family history CRC:
     • full colonoscopy and other indicated evaluations
Bright Red Blood Per Rectum
• Complications

  – Patient discomfort/embarressment

  – Iron deficiency anemia
Iron Deficiency Anemia
• You will learn in hematology next week
  how to diagnose iron deficiency anemia

• This is a common problem that is often
  referred to gastroenterologists

• Today lets look at this problem in more
  detail to learn how to determine the cause
  of iron deficiency anemia in patient
Iron Deficiency Anemia
• Why does iron deficiency lead to anemia?

• Why does iron deficiency occur?
Iron Deficiency and Anemia
• Recall the structure of
  hemoglobin                                           Hemo-
                                                       globin
• Recall the role of iron in
  binding and releasing
  oxygen from hemoglobin
                                Julian Voss-Andreae, Wikimedia Commons



• No iron = no erythrocytes
                                                    Heme
• Iron deficiency = fewer and                       ring with
  smaller erythrocytes                              oxygen
Iron Cycle: Facts
• Iron is high toxic at high concentrations
  – Therefore absorption of iron is tightly
    controlled
• Iron is absorbed by the duodenal mucosa
• Iron is efficiently recycled between RBCs,
  the reticuloendothelial system and the
  bone marrow
• Daily loss is about 1 mg a day
Normal Balance of Iron             Dietary iron                         Iron Pools
                                (5-15 mg elemental,
                                   1-5 mg heme)
                                                                            Tissues
                                                               300 mg




                                                                            Storage
                                                            100 – 400 mg
                                                              in women
                                                               1000 mg
                                                                in men


                                            Absorption of                  Red cells
                                            1 mg of iron




                                                                   Normal
         Loss of                                                   2500 mg
       1 mg of iron


       Medium69

                      Obligate loss: ~1 mg of iron from ~1 ml of blood and other losses
Iron Storage/Transport
• Iron is not very water soluble
• It is transported in blood to and from
  tissues bound to transferrin
• Iron is stored in cells by the protein ferritin
• Measurements of body iron stores
  – Percent transferrin saturation (Fe/total iron
    binding capacity x 100)
  – Serum ferritin concentration
Iron cycle reviewed:

1) 1 unit of blood = 250 mg iron - thus ~1/10 of a unit is recycled daily

    2) iron absorption and recycling is controlled by liver/hepcidin
FYI: Genetic Hemochromatosis




   1. A disease of uncontrolled iron absorption from the duodenum
   2. Due to mutations that disrupt liver sensing of body iron stores
   3. Hepcidin is suppressed and iron absorption is increased.
Today:
   Approach to Iron Deficiency
          +/- Anemia
• How do you identify iron deficiency?
• Why does iron deficiency develop?
• How do you evaluate causes of iron
  deficiency in patients?
• How do you treat iron deficiency?
Identification of Iron Deficiency

• Low ferritin
  – < ~100 ng/ml
• Low saturation of iron binding proteins
  – Iron/TIBC < 15-20%
• Microcytic anemia
  – MCV (mean corpuscular volume) < 80-85
• Thrombocytosis (in severe cases)
• Absence of iron in the bone marrow
Etiology of Iron Deficiency
• Loss of blood

• Inadequate dietary intake

• Failure to absorb iron
Etiology of Iron Deficiency
• Loss of blood
   – Menstrual losses/childbirth

   –Gastrointestinal blood loss
   – Hematuria


• Inadequate diet (rare in USA)

• Failure to absorb iron
   – Celiac sprue
   – Loss of duodenal surface area (surgical scar present)
Gastrointestinal Blood Loss and Iron Balance
Normal Balance of Iron                                                                               Iron Deficiency
                              Dietary iron                                      Dietary iron
                          (5-15 mg elemental,                                 (5-15 mg elemental,
                             1-5 mg heme)              Iron Pools                1-5 mg heme)
                                                                                  absorption
                                                                              increases 2-3 times
                                                      Tissues
                                                    300 mg            300 mg




                                                          Storage
                                                100 – 400 mg
                                                  in women
                                                   1000 mg             None
                                                    in men


                                    Absorption of                              Absorption
                                    1 mg of iron
                                                     Red cells                 increases


                                                 Normal
      Loss of                                                       Deficient           3-5 mg of iron
    1 mg of iron
                                                 2500 mg                                                          Loss of
                                                                   < 2000 mg        (i.e., gastrointestinal,    1 mg of iron
                                                                                            menses)
    Medium69
                   Obligate loss: ~1 mg of iron = ~1 ml of blood (~0.5 mg of iron) + ~0.5 mg of nonblood iron



 Additional loss of blood/iron cannot be matched by gut
 absorption and iron deficiency/anemia worsens
Evaluation of Iron Deficiency
• Find source of blood loss
  – GI evaluation is most important
  – Check for hematuria
• Ask patient about diet
• Ask patient about surgery on stomach or
     duodenum (? iron malabsorption)
• Look for malabsorption (celiac sprue)
Evaluation in USA
• Iron deficency in men is always pathologic: must
  evaluate
• Prior to menopause, women are frequently iron
  deficient: evaluate if severe or if other clinical
      clues to disease are present
• GI blood loss accounts for most iron deficiency
  outside of menstrual/birth losses
  – always work up GI tract
  – fecal occult blood tests of little value as they are
    insensitive and non-specific. If patients are iron
    deficiency, we have to look for blood loss no matter
    what the results of fecal occult blood tests are.
GI Evaluation:               Iron deficiency anemia

                                              Pick order based on
                  Colonoscopy                     clinical clues
               Upper endoscopy                  Can do together
                                              Identifies most cases
           Small bowel biopsy (sprue)
           Transglutaminase antibody
                        +          -
                                           Dedicated small bowel
 Treat underlying                            series
   disease                                 Capsule endoscopy
                                           Meckel’s scan
                    Give oral iron
                    Monitor response
                    If poor response,
                        consider IV iron
Most recent recommendations:
depend on availability of capsule endoscopy




      AGA position statement. Gastroenterology 133:1694, 2007
Iron Administration
• Oral iron may work if patients are
  nutritionally deficiency or are losing blood
  only slowly
  – Follow patient carefully to make sure its
    working (what tests would you follow?)
  – Be patient – it can take 6-12 months to re-
    establish normal iron stores from oral intake.
• If patient cannot absorb oral iron, IV iron
  must be given
IV Iron
• Iron dextran – oldest form
  – May give 1-1.5 grams of iron at a single infusion
  – Rare but real anaphylaxtic reactions


• Iron sucrose (Venofer) or sodium ferric
  gluconate complex (Ferrlecit)
  – Developed for use as small doses (100-125 mg) given
    by rapid IV push for dialysis patients
  – Can give 200-500 mg at a single infusion if necessary


• In iron deficiency you have to replace the
  missing erythrocytes AND storage pool.
• In this sequence you have learned
  about a large number of GI diseases
• Some present with inflammation and/or
  iron deficiency or both.
• Some have cures,some are chronic
  diseases with consequences
• Today we have a patient to help us
  understand the patient perspective of
  some of these problems.
Additional Source Information
                              for more information see: http://open.umich.edu/wiki/CitationPolicy

Slide 14: Julian Voss-Andreae, Wikimedia Commons, http://upload.wikimedia.org/wikipedia/commons/6/68/Heart_of_Steel_(Hemoglobin).jpg
CC:BY-SA, http://creativecommons.org/licenses/by-sa/3.0/deed.en

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02.09.12: A GI Smorgasbord - Common GI Problems part II

  • 1. Author(s): Rebecca W. Van Dyke, M.D., 2012 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution – Share Alike 3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  • 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  • 3. M2 GI Sequence A GI Smorgasbord: Common GI Problems Rebecca W. Van Dyke, MD Winter 2012
  • 4. Industry Relationship Disclosures Industry Supported Research and Outside Relationships • None
  • 5. Topics • Bright red blood per rectum • Iron deficiency anemia • Patient presentation: IBD and disease/surgical issues from a patient perspective
  • 6. Bright Red Blood Per Rectum A common problem seen in most areas of medicine
  • 7. Bright Red Blood Per Rectum • Passage of small amounts of BRBPR is common – Affects at least 20% of general public at one time or another – Usually trivial, but can reflect serious disease • BRBPR – location – On toilet paper – Streaks on stool – Dripping into toilet bowl – On underwear
  • 8. Bright Red Blood Per Rectum • Differential diagnosis: – think types of diseases that could cause small amounts of bleeding – usually in distal colon or anorectal area: • Trauma • Neoplasia • Infection/inflammatory • Vascular
  • 9. Bright Red Blood Per Rectum • Diagnoses after full investigation: – 20+%: Nothing found – presumably tissue tears had healed at the time of investigation – 50+%: Anorectal disease Hemorrhoids Anal fissures Trauma with tissue tears (ask patient ) – 20-40%: Polyps (hyperplastic/adenomatous) – 2-7%: Colon cancer (increase with age) – 5-15%: Inflammatory bowel disease – 2-5%: Vascular lesions arteriovascular malformations (AVMs) – 1%: Benign ulcers NSAIDS, stercoral related to chronic constipation
  • 10. Bright Red Blood Per Rectum • Goal: Find a disease you would treat • Evaluation – little evidence to guide you – Can do full colonoscopy in everyone – Alternative: no clues to disease, no family history of CRC: • <40, reassure or just do flex sig and Rx constipation • 40-49: flex sig or colonoscopy • >50: full colonoscopy – If disease clues (diarrhea, frequent/continued bleeding, iron deficiency, pain) or family history CRC: • full colonoscopy and other indicated evaluations
  • 11. Bright Red Blood Per Rectum • Complications – Patient discomfort/embarressment – Iron deficiency anemia
  • 12. Iron Deficiency Anemia • You will learn in hematology next week how to diagnose iron deficiency anemia • This is a common problem that is often referred to gastroenterologists • Today lets look at this problem in more detail to learn how to determine the cause of iron deficiency anemia in patient
  • 13. Iron Deficiency Anemia • Why does iron deficiency lead to anemia? • Why does iron deficiency occur?
  • 14. Iron Deficiency and Anemia • Recall the structure of hemoglobin Hemo- globin • Recall the role of iron in binding and releasing oxygen from hemoglobin Julian Voss-Andreae, Wikimedia Commons • No iron = no erythrocytes Heme • Iron deficiency = fewer and ring with smaller erythrocytes oxygen
  • 15. Iron Cycle: Facts • Iron is high toxic at high concentrations – Therefore absorption of iron is tightly controlled • Iron is absorbed by the duodenal mucosa • Iron is efficiently recycled between RBCs, the reticuloendothelial system and the bone marrow • Daily loss is about 1 mg a day
  • 16. Normal Balance of Iron Dietary iron Iron Pools (5-15 mg elemental, 1-5 mg heme) Tissues 300 mg Storage 100 – 400 mg in women 1000 mg in men Absorption of Red cells 1 mg of iron Normal Loss of 2500 mg 1 mg of iron Medium69 Obligate loss: ~1 mg of iron from ~1 ml of blood and other losses
  • 17. Iron Storage/Transport • Iron is not very water soluble • It is transported in blood to and from tissues bound to transferrin • Iron is stored in cells by the protein ferritin • Measurements of body iron stores – Percent transferrin saturation (Fe/total iron binding capacity x 100) – Serum ferritin concentration
  • 18. Iron cycle reviewed: 1) 1 unit of blood = 250 mg iron - thus ~1/10 of a unit is recycled daily 2) iron absorption and recycling is controlled by liver/hepcidin
  • 19. FYI: Genetic Hemochromatosis 1. A disease of uncontrolled iron absorption from the duodenum 2. Due to mutations that disrupt liver sensing of body iron stores 3. Hepcidin is suppressed and iron absorption is increased.
  • 20. Today: Approach to Iron Deficiency +/- Anemia • How do you identify iron deficiency? • Why does iron deficiency develop? • How do you evaluate causes of iron deficiency in patients? • How do you treat iron deficiency?
  • 21. Identification of Iron Deficiency • Low ferritin – < ~100 ng/ml • Low saturation of iron binding proteins – Iron/TIBC < 15-20% • Microcytic anemia – MCV (mean corpuscular volume) < 80-85 • Thrombocytosis (in severe cases) • Absence of iron in the bone marrow
  • 22. Etiology of Iron Deficiency • Loss of blood • Inadequate dietary intake • Failure to absorb iron
  • 23. Etiology of Iron Deficiency • Loss of blood – Menstrual losses/childbirth –Gastrointestinal blood loss – Hematuria • Inadequate diet (rare in USA) • Failure to absorb iron – Celiac sprue – Loss of duodenal surface area (surgical scar present)
  • 24. Gastrointestinal Blood Loss and Iron Balance Normal Balance of Iron Iron Deficiency Dietary iron Dietary iron (5-15 mg elemental, (5-15 mg elemental, 1-5 mg heme) Iron Pools 1-5 mg heme) absorption increases 2-3 times Tissues 300 mg 300 mg Storage 100 – 400 mg in women 1000 mg None in men Absorption of Absorption 1 mg of iron Red cells increases Normal Loss of Deficient 3-5 mg of iron 1 mg of iron 2500 mg Loss of < 2000 mg (i.e., gastrointestinal, 1 mg of iron menses) Medium69 Obligate loss: ~1 mg of iron = ~1 ml of blood (~0.5 mg of iron) + ~0.5 mg of nonblood iron Additional loss of blood/iron cannot be matched by gut absorption and iron deficiency/anemia worsens
  • 25. Evaluation of Iron Deficiency • Find source of blood loss – GI evaluation is most important – Check for hematuria • Ask patient about diet • Ask patient about surgery on stomach or duodenum (? iron malabsorption) • Look for malabsorption (celiac sprue)
  • 26. Evaluation in USA • Iron deficency in men is always pathologic: must evaluate • Prior to menopause, women are frequently iron deficient: evaluate if severe or if other clinical clues to disease are present • GI blood loss accounts for most iron deficiency outside of menstrual/birth losses – always work up GI tract – fecal occult blood tests of little value as they are insensitive and non-specific. If patients are iron deficiency, we have to look for blood loss no matter what the results of fecal occult blood tests are.
  • 27. GI Evaluation: Iron deficiency anemia Pick order based on Colonoscopy clinical clues Upper endoscopy Can do together Identifies most cases Small bowel biopsy (sprue) Transglutaminase antibody + - Dedicated small bowel Treat underlying series disease Capsule endoscopy Meckel’s scan Give oral iron Monitor response If poor response, consider IV iron
  • 28. Most recent recommendations: depend on availability of capsule endoscopy AGA position statement. Gastroenterology 133:1694, 2007
  • 29. Iron Administration • Oral iron may work if patients are nutritionally deficiency or are losing blood only slowly – Follow patient carefully to make sure its working (what tests would you follow?) – Be patient – it can take 6-12 months to re- establish normal iron stores from oral intake. • If patient cannot absorb oral iron, IV iron must be given
  • 30. IV Iron • Iron dextran – oldest form – May give 1-1.5 grams of iron at a single infusion – Rare but real anaphylaxtic reactions • Iron sucrose (Venofer) or sodium ferric gluconate complex (Ferrlecit) – Developed for use as small doses (100-125 mg) given by rapid IV push for dialysis patients – Can give 200-500 mg at a single infusion if necessary • In iron deficiency you have to replace the missing erythrocytes AND storage pool.
  • 31. • In this sequence you have learned about a large number of GI diseases • Some present with inflammation and/or iron deficiency or both. • Some have cures,some are chronic diseases with consequences • Today we have a patient to help us understand the patient perspective of some of these problems.
  • 32. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 14: Julian Voss-Andreae, Wikimedia Commons, http://upload.wikimedia.org/wikipedia/commons/6/68/Heart_of_Steel_(Hemoglobin).jpg CC:BY-SA, http://creativecommons.org/licenses/by-sa/3.0/deed.en

Notas do Editor

  1. Figure 2. Gastrointestinal Blood Loss and Iron Balance. Normal obligate daily iron loss is from blood loss (presumably from gastrointestinal mucosal microerosions or microulcerations) and iron in sloughed epithelial cells of the gut. Total daily iron loss is approximately 1 mg. The usual Western diet contains mostly elemental iron, of which about 10 percent is absorbed. Heme iron, derived primarily from myoglobin in meats, is preferentially absorbed and accounts for 60 to 80 percent of the iron absorbed per day. Under normal circumstances, iron homeostasis is tightly regulated, and daily iron loss is precisely balanced by iron absorption. Iron deficiency results only when the dynamic, but limited, absorptive capacity of the small intestine is exceeded by iron loss. The time required for the development of iron deficiency depends on the size of initial iron stores, the rate of bleeding, and intestinal iron absorption. Iron deficiency generally occurs only with loss of more than 5 ml of blood per day. Anemia is a late manifestation of the iron-depleted state. The red cells indicate bleeding and potential sites of blood loss.