Renal disorders, especially nephrolithiasis, are observed in one-third of patients with Crohn’s disease, probably related to increased oxalate absorption associated with calcium-oxalate-stonesteatorrhea.

HOW? Inflammation or resection affecting the terminal ileum may result in malabsorption of bile acids this will inevitably affect fat absorption.

Increased intestinal fat binds dietary calcium, which is then unavailable to bind oxalate (a type of salt). Oxalate is free to be absorbed in the GI tract -> Blood stream -> re-deposited in the kidney (hyperoxaluria), where it can form calcium oxalate stones.

REFERENCES

  1. Cury DB, Moss AC, Schor N. Nephrolithiasis in patients with inflammatory bowel disease in the community. International Journal of Nephrology and Renovascular Disease. 2013;6:139-142. doi:10.2147/IJNRD.S45466.
  2. Ch 13: Gastrointestinal Disease. Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e. Jason C. Mills, MD, PhD, AGAF; Thaddeus S. Stappenbeck, MD, PhD
how-urea-breath-test-works
Copyright ©1995 Massachusetts Medical Society. All rights reserved.

H. pylori that colonizes the gastric mucosa will produce an enzyme called Urease (catalyzes the breakdown of urea to produce ammonia + carbamate). 

The labeled Carbon-13 isotope urea breath test has become the gold standard to confirm eradication of H. pylori following appropriate treatment because serology will remain positive even after cure.

In this test, the patient drinks an urea solution (~100-200mL) containing a nonradioactive 13-Carbon isotope. Normally gastric urea is virtually all 12-Carbon isotope. If H. pylori Urease is present, the 13C-urea is hydrolyzed and the radiolabeled 13-Carbon dioxide is excreted from the lungs and can be detected in the patient’s expired breath around 30 minutes later. (Only detected if Urease breaks it down)

Samples are sent for mass spectrometry and elevated concentrations of 13-Carbon isotope is considered positive for H. pylori (96% sensitivity and 100% specificity) [3]. 

REFERENCES

  1. Chapter 26: Stomach. Schwartz’s Principles of Surgery, 10e. Yuko Kitagawa; Daniel T. Dempsey
  2. Mobley HLT. Urease. In: Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001. Chapter 16.
  3. Berger A. Helicobacter pylori breath tests. BMJ : British Medical Journal. 2002;324(7348):1263.

Ascites: Defined as free fluid in the abdominal cavity. The fluid wave is a very specific test (82-92%) for detecting ascites. It is performed by having the patient (or assistant) place the medial side of their hands onto the abdominal midline. The examiner then taps the left or right flank sharply while using the opposite fingertips to try to detect the impulse on the contra-lateral flank.

WHY THE HANDS ON THE STOMACH? To stop the transmission of the impulse wave through subcutaneous fat.

fluid-wave

REFERENCES

  1. John W. Williams Jr, MD; David L. Simel, MD, MHS. Does This Patient Have Ascites?. JAMA. 1992;267(19):2645-2648. doi:10.1001/jama.1992.03480190087038.Text Size: A A A

Patients with alcoholic hepatitis almost always have liver markers levels less than 500 IU/L and often have a ratio AST/ALT of 2:1. Elevated gamma-glutamyl transferase supports the diagnosis.

THEORY:
1. ALT= Liver cytoplasmic enzyme (specific for liver cell necrosis). AST= mitochondrial enzyme

  • Ethanol (Alcohol) damages the mitochondrial membrane, which is critical to dealing with reactive oxygen species (ROS). Excess ethanol may overwhelm the mitochondria with oxidative stress leading to cellular damage/death. This in term causes increased leakage of mitochondria AST (mAST) into the bloodstream.

2. Decreased ALT activity most likely due to B6 depletion in the livers of alcoholics

REFERENCES

  1. Botros M, Sikaris KA. The De Ritis Ratio: The Test of Time. The Clinical Biochemist Reviews. 2013;34(3):117-130.
  2. Matloff DS, Selinger MJ, Kaplan MM. Hepatic transaminase activity in alocholic liver disease. Gastroenterology. 1980 Jun; 78(6):1389-92.
  3. Ishii H, Okuno F, Shigeta Y, Tsuchiya M. Enhanced serum glutamic oxaloacetic transaminase activity of mitochondrial origin in chronic alcoholics. Curr Alcohol. 1979; 5():101-8.
  4.  Serum gamma-glutamyl transpeptidase and chronic alcoholism. Influence of alcohol ingestion and liver disease. Dig Dis Sci 30 (3): 211–4. Mar 1985. doi:10.1007/bf01347885. PMID 2857631.

Gastric acid inhibitors [Proton Pump Inhibitor (PPIs) & Histamine 2 receptor antagonists (H2RAs)] is associated with vitamin B12 deficiency; especially in the elderly.  Vitamin-B12-absorption

WHY??? Vitamin B12 absorption requires peptic enzymes to cleave dietary B12 from dietary proteins and to allow for absorption in the distal Ileum.

THEORY: This is performed primarily by pepsin, which requires gastric acid to activate it from its pepsinogen precursor. Therefore in the setting of reduced gastric acid secretion, vitamin B12 will not be cleaved and can not bind to R-proteins in the stomach. This step is required to protect vitamin B12 from pancreatic digestion. Also, parietal cells which generate HCl (via K+/H+ APTase pump) produce intrinsic factor, a compound required for vitamin B12 absorption in the distal ileum. (see image on right)

NOTE: conditions associated with vitamin B12 deficiency (ie, thyroid disease, Helicobacter pylori infection, alcohol abuse, smoking, atrophic gastritis, and achlorhydria), may be confounding!

REFERENCES

  1. Lam JR, Schneider JL, Zhao W, Corley DA. Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA. 2013;310(22):2435-2442. doi:10.1001/jama.2013.280490.
  2. Festen, HP. Intrinsic factor secretion and cobalamin absorption. Physiology and pathophysiology in the gastrointestinal tract. Scand J Gastroenterol Suppl. 1991; 188():1-7.
  3. Howden, CW. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J Clin Gastroenterol. 2000 Jan;30(1):29-33.

Differential Dx of Signs and Symptoms

SYMPTOMS Crohn’s Disease Ulcerative Colitis
Defecation Will present porridge-like stool and possibly fatty diarrhea (steatorrhea) Mucus like and will often PRESENT WITH BLOOD/PUS (90%)
Tenesmus Less Common More Common
Fever Common (Affects everywhere) Less Common (would indicate a severe disease state)
SYSTEMIC MARKERS (CRP, Erythrocyte Sedimentation Rate [ESR], Common (Affects everywhere) Less Common (would indicate a severe disease state)
Weight loss Common Less Common
BOTH: will often have often vomiting, diarrhea and bleeding from the rectum

 

Differential Dx of Histologic/ Pathologic Findings

FINDING Crohn’s Disease Ulcerative Colitis
Inflammation in Terminal Ileus Usually Almost never
Colon Involvement Usually 100% (50% if just colon/ rectum, 30% until left splenic flexure, 20% is the entire colon)
Rectum Involvement Almost never Always
Continuous or Skipping SKIPPING (skip lesions) CONTINUOUS
Higher Rate Of Primary Sclerosing Cholangitis No YES
Depth of the Disease Transmural Contained within the mucosal layer
Strictures and Fistulas Yes No
Granuloma If present, it will rule out UC and give diagnosis of Crohn’s if symptoms fit Never
Abdominal Masses May have one in RLQ Almost Never
Toxic Megacolon No Yes
     
       

Extensive bleeding from the upper gastrointestinal (GI) tract will cause an increase in Urea (BUN).

HOW? Blood is full of proteins (i.e Hemeglobin, Immunoglobins) which are absorbed in the GI tract. Since it is an upper GI bleed (above the ligament of treitz) there is time for adequate absorption.

  • Blood Urea Nitrogen (BUN) reflects the end product of the metabolic breakdown of protein
  • Hence when there is bleeding => protein breakdown & absorption => increase in Urea

*It is often debated that a GI bleed (if severe enough) can also result in hypovolemia -> causing prerenal azotemia and raise the BUN

NOTE: Cannot be utilized in the setting of diuretics or CKD

References

  1. Witting MD, Magder L, Heins AE, Mattu A, Granja CA, Baumgarten M (May 2006). “ED predictors of upper gastrointestinal tract bleeding in patients without hematemesis”. Am J Emerg Med 24 (3): 280–5. doi:10.1016/j.ajem.2005.11.005. .

Cutaneous hyperpigmentation can be present in 70% of patients due to two different mechanisms:

(1) hemosiderin deposition => diffuse, slate-gray darkening of skin

(2) increased production of melanin in the epidermis (this is what causes bronzing hyperpigmentation!!!)

If you get asked = the visible pigmentation (aka bronzing) manifests due to increased melanin in the basal layer of the epidermis. [1]

References

1. Pietrangelo A. Hereditary hemochromatosis—a new look at an old disease. N Engl J Med. 2004;350(23):2383–2397. [PubMed]

Current serological testing detects the IgA isotype of the Anti-TTG antibodies. Hence if a person is IgA deficient they will lack the prerequisite antibodies for testing despite the possibility of Celiac disease. The IgG class of anti-tTG may be ordered as an alternative in those who have a deficiency of IgA. Approximately 2-3% of the time in people with Celiac disease there is concurrent IgA deficiency and can lead to false-negative test results. [1]

References

1. Rittmeyer, C., Rhoads, J. M. 1996. IgA deficiency causes false-negative endomysial antibody results in celiac disease. J. Pediatr. Gastroenterol. Nutr. 23:504-506.