L-5 Fatigue, Headaches, and Shortness of Breath

• Gina Foster-Moumoutjis, MD, is an Associate Professor of Family Medicine at Dr. Kiran C Patel College of Osteopathic Medicine, Nova Southeastern University.

HPI Key Points

• Slowly progressive fatigue, headaches, muscle cramps, and shortness of breath with exertion are present.
• Symptoms worsen with exertion and improve with rest; they were first noticed one week prior.
• Symptoms limit daily activity, such as headaches when walking upstairs and inability to complete athletic workouts.
• Pertinent negatives include no chest pain, diaphoresis, cough, or wheezing.

Medical History

• No medical or surgical problems, but a history of radius fracture.
• Family history includes a mother with hyperthyroidism and a healthy father.
• Social history includes no ETOH, drugs, or tobacco use; not currently sexually active, daily exercise, and a well-balanced diet.
• Ibuprofen is taken as needed for dysmenorrhea.
• No known allergies.
• Negative ROS: no hair or skin changes, weight gain or loss, insomnia, fevers, or chills.

Physical Examination

• BP: 92/56, HR 95, RR: 12, O2Sat 99%
• Well-appearing female with good hygiene and no apparent distress.
• Normal heart sounds with no murmurs.
• Clear to auscultation bilaterally with no wheezes, rales, or rhonchi.
• Abdomen with normal bowel sounds, nontender, and no organomegaly.
• No thyroid enlargement or palpable lymphadenopathy in the neck.
• Palmar and conjunctival pallor are noted.

Initial Lab Results

• Complete Blood Count (CBC) includes white blood cells, hemoglobin, hematocrit, and platelets.
• Hemoglobin is low at 8.1.
• Hematocrit is low at 29.
• MCV (mean corpuscular volume) is low.
• White blood cells are normal at 8.
• Platelets are normal at 275.
• The blood disorder present is microcytic anemia.

Follow-up Labs

• Fecal Occult Blood Test (FOBT) result is positive.
• Serum iron is low.
• Ferritin is low.
• Total Iron Binding Capacity(TIBC) is high.
• % Saturation is low.

Peripheral Smear

• Peripheral smear may show hypochromic microcytosis, anisocytosis, and poikilocytosis.

Iron Circulation

• Iron is absorbed through the gut & transported across the cell membrane via ferroportin.
  • It binds to transferrin.
  • Hepcidin downregulates transport across ferroportin.
• Old red blood cells processed by reticuloendothelium (RE) which removes and presents iron back to transferrin.
• Iron is released from stores in tissues or cells (liver, RE) to transferrin.
• Iron binds to transferrin, transported through the blood, and delivered to the bone marrow.
• Iron is used in bone marrow erythroid cells for hemoglobin production, with excess stored as ferritin.
• Total iron is the amount of circulating iron bound to transferrin.
• TIBC is an indirect measure of circulating transferrin.
• % Saturation is the percentage of transferrin binding iron.
• Serum Ferritin reflects the amount of ferritin stored in tissues/cells.
  • Free iron bound to apoferritin equals ferritin.
  • Storing as ferritin prevents damage because unbound iron can be dangerous to cells.

Evolution of Iron Labs

• Negative iron balance means iron stores start to deplete
  • TIBC increases
  • Serum ferritin decreases.
• Iron-deficient erythropoiesis means that transferrin saturation decreases to less than 20% and serum iron (SI) decreases.
• Iron-deficiency anemia presents as microcytosis and anemia.
• Ferritin and TIBC change first in patients with iron loss.
• In iron loss, TIBC increases.
• Compared to negative iron balance, iron-deficient erythropoiesis presents with changes in serum iron (SI), % saturation, and RBC protoporphyrin.

Microcytic Anemia Differential Diagnosis

• Iron deficiency anemia involves decreased marrow iron and depleted body iron stores.
• Anemia of chronic disease involves decreased RBC production due to impaired iron utilization and functional iron deficiency from increased hepcidin.
• Thalassemia involves decreased synthesis of alpha or beta globin chains of Hb, as well as anemia secondary to hemolysis and decreased erythropoiesis.
• Sideroblastic anemia involves defective heme biosynthesis within RBC precursors.

Causes of Iron Deficiency

• Increased demand occurs with rapid growth, pregnancy/lactation, erythropoietin therapy, tumors, and chronic infection.
• Iron loss occurs with chronic blood loss (GI, urinary tract, uterine abnormality), menorrhagia, blood donation, and acute blood loss.
• Reduced absorption may be caused by inadequate dietary intake, malabsorption from disease or surgery, acute/chronic inflammation, and medications (PPI, H2 blocker).

GI Bleeds

• The GI tract can be divided into Upper and Lower, with the division point being at the Ligament of Treitz.
• Upper GI includes the esophagus, stomach, and duodenum.
• Lower GI includes the jejunum, ileum, colon, rectum, and anus.

Clinical Presentation of Bleeds

• Upper GI bleeds:
  • Hematemesis
  • Coffee ground emesis
  • Nausea/Vomiting
  • Epigastric Pain
  • Melena
  • Syncope
• Lower GI bleeds:
  • Bright red blood per rectum
  • Hematochezia
  • Tenesmus
  • Diarrhea
  • Severity of symptoms depends on volume and rate of blood loss.

Causes of Bleeds

• Upper GI causes:
  • Peptic or duodenal ulcers
  • Gastritis
  • Mallory Weiss tear
  • Esophageal varices
  • Cancer
  • gastric, esophageal
  • Aortoenteric fistula
  • NSAID gastropathy Lower GI causes:
  • Hemorrhoids
  • Fissure
  • Colorectal cancer
  • Crohn's disease
  • Diverticula
  • Colitis
  • infectious
  • Vascular ectasia

Differential Diagnosis of GI Bleed Using VINDICATES

• VASCULAR: Vascular ectasia, esophageal varices, hemorrhoids.
• INFECTIOUS OR INFLAMMATORY: Infectious colitis, Crohn's colitis, Gastritis.
• NEOPLASTIC OR NEUROLOGIC: Colon cancer, gastric cancer, anorectal cancer.
• DEGENERATIVE, DEFICIENCIES, DESTRUCTION, DRUGS.
• IATROGENIC OR IDIOPATHIC: NSAID gastropathy, Aspirin.
• CONGENITAL OR GENETIC: Meckel's diverticulum, intussusception.
• AUTOIMMUNE OR ALLERGY: Celiac disease.
• TRAUMA OR DYSFUNCTION: Mallory Weiss tear, anal fissure.
• ENDOCRINE OR METABOLIC.
• SOCIAL OR PSYCH: Alcoholic gastritis.
• Additional questions for HPI: - Have you seen blood in your stool? - Has your stool changed in color or consistency? - Does your stool have a dark black appearance? - Are you taking any supplements like iron or Pepto-Bismol? - Do you have any abdominal pain? - Do you have GERD? - Have you ever had hemorrhoids? - Do you bleed from your gums when brushing teeth? - Any vomiting?

Diagnostic Procedures

• EGD, Biopsy, and Testing for H. pylori can further investigate GI bleeds

Treatment

• Iron Deficiency Anemia treatment includes oral supplementation with ferrous sulfate 325 mg three times a day, every other day (total of 195 mg of elemental iron daily).
  • Increased dietary intake of iron-rich foods.
  • Repeat CBC in 2 weeks, then at 4 weeks check CBC and iron studies; continue to monitor until ferritin and % saturation normalize.

Gastritis Treatment

• Omeprazole (proton pump inhibitor) 20 mg twice daily for 1 month (normal dosing is once daily).
• Discontinue use of NSAIDs.
• Start oral contraceptive for menstrual cramps.

Learning Objectives

• Identify the clinical presentation of anemia.
• Understand the internal iron exchange and the role of iron in hemoglobin synthesis.
• List differential diagnoses in iron deficiency.
• Form a plan for the evaluation of iron deficiency anemia.
• Recognize lab differences in negative iron balance, iron deficient erythropoiesis, and iron deficiency anemia.
• Recognize the difference between symptomatic presentations of upper and lower GI bleeds.