Objective 10 and 43 (a lot of diseases)

What is the etiology of IDA?

• inadequate intake

• increased need

• impaired absorption

• chronic blood loss

What are symptoms of IDA?

• fatigue, irritability, headache, weakness, shortness of breath, tachycardia, pale skin color

• Severe Symptoms

  • Koilonychias

  • Cheilitis

  • Glossitis

  • PICA

  • muscle dysfunction

What lab findings indicate IDA?

• ↑ TIBC and Transferrin

  • because body is making more transporters waiting for Fe to show up

• ↓ Hgb, MCV, iron, ferritin, % saturation

• microcytic / hypochromic

• prussian blue stain: NEGATIVE

WHat can be used to treat IDA?

• treat underlying cause

  • oral supplements

    • ferrous sulfate

    • iron dextran parenteral administration

    • monoferic - given IV

  • RBC transfusion - does NOT fix Fe deficiency

How can you measure response to IDA treatment?

• reticulocyte Hb content

• relative / absolute reticulocyte counts

• Hgb and MCV

• peripheral film smear

What is the etiology of Sideroblastic Anemia?

• defective incorporation of iron into hemoglobin

  • iron is present BUT cant be used

  • accum. of iron in erythroid cells

  • ineffective erythropoiesis

  • increase in serum / tissue iron

  • microcytic / hypochromic

• iron deposits in mitochondria of erythrocytes

What can cause Sideroblastic anemia?

• Congenital - rare

• Aquireed

  • Primary

    • myelodysplastic syndrome with ringed sideroblasts in BM

  • Secondary

    • Lead - rare

      • blocks heme synthesis

      • basophilic stipplings

      • no ringed sideroblasts

    • drugs / alcohol

These images are indicative of what disease?

• iron deficiency Anemia

What are symptoms of Sideroblastic Anemia?

• weakness, fatigue, palpitations, shortness of breath, pale skin, headaches

• Hepatomegaly / splenomegaly

• cognitive impairment with lead exposure

What is the hallmark lab finding for Sideroblastic anemia?

• ringed sideroblasts

What can be seen on a blood smear for Sideroblastic Anemia?

• anisocytosis

• poliocytosis

• target cells

• pappenheimer bodies

• basophilic stipplings

• ringed sideroblasts

  • ONLY in BM

  • Fe accumulation in mitochondria

  • dots around nucleus

What treatment is used for Sideroblastic Anemia?

• Pyridoxine (B6)

• Transfusion

What lab findings indicate Sideroblastic Anemia?

• ↓ Hgb and RBC

• dimorphic RBC

• ↑ RDW

• normal / ↓ transferrin / TIBC

• ↑ iron, ferritin, % saturation

What is the etiology of Anemia of Chronic Inflammation?

• 2nd most common cause of anemia

  • “iron exists BUT it is locked away”

• due to chronic conditions / infections

  • hospitalized patients

  • autoimmune conditions

  • long term immune activation

  • ↑ levels of hepcidin

    • locks iron in storage / hides it from chronic disease

What is used to treat Anemia of Chronic Inflammation?

• treat underlying disease

• Erythropoietin

• Ferrous sulfate

What lab testing can indicate Anemia of Chronic Inflammation?

• microcytic/normocytic and hypochromic / normochromic

• ↓ serum iron, transferrin, % saturation, TIBC

• normal / ↑ ferritin

• prussian blue stain: positive

What is an easy way to distinguish IDA and anemia of chronic inflammation?

• Transferrin

  • decreased in ACI

  • increased in IDA

What is the etiology of Hereditary Hemochromatosis?

• recessive genetic disorder causes the body to absorb too much iron from the intestines

• hepcidin deficiency

What are clinical findings of Hereditary Hemochromatosis?

• Early symptoms

  • fatigue

  • joint paint

  • bronze discoloration of skin

• later symptoms

  • hepatomegaly → leads to cirrhosis and fibrosis of liver

  • iron deposits in heart tissue → cardiomyopathy

  • diabetes mellitus, hypopituitarism, hypogonadism, hyoparathryoidism

What lab testing can indicate Hereditary Hemochromatosis?

• ↑ liver function enzyme tests

• ↑ serum iron , ferritin , transferrin

What is used to treat Hereditary Hemochromatosis?

• Therapeutic phlebotomy

  • chelating agents can be used to reduce iron stores if phlebotomy is not appropriate

What is the etiology of Megaloblastic Anemia?

Root Cause

• impaired DNA synthesis

• defective nuclear maturation

Deficiencies of vitamin B12 / folate

What are symptoms of Megaloblastic anemia?

• weakness, fatigue, shortness of breath

• lightheadedness

• yellow skin tint - mild jaundice

What can be used to measure the response to treatment for Megaloblastic Anemia?

• Increased reticulocyte count

  • may take weeks

What treatment is used for Megaloblastic anemia?

• directed towards specific vitamin deficiency

  • pernicious anemia - cobalamin given IM

  • folic acid given orally

• after therapy:

  • bone will reflect normoblastic cells

  • peripheral blood retic will normalize in 1 week

  • H/H will normalize in 3 weeks

What can be seen on a blood smear that would indicate Megaloblastic anemia?

• tear drop cells

• RBC fragments

• Howell jolly bodies

• cabot rings

What lab findings would indicate Megaloblastic anemia?

• decreased H/H

• macrocytosis

• pancytopenia

• MCV: 100 - 150 fl

• high RDW

• Hypersegs

What is the Etiology of Hereditary Spherocytosis?

• vertical defect: connect the membrane skeleton and lipid bilayer

  • if these are defected, the RBC loses pieces of its membrane

• group of hemolytic anemias caused by vertical interactions between RBC membrane skeleton and lipid bilayer

• protein defects disrupt vertical interactions

  • spectrin, ankyrin, band 3, protein 4.2

Describe the pathophysiology of Hereditary Spherocytosis.

Primary membrane cytoskeleton defect → loss of membrane due to decreased stability → decreased surface: volume ratio → spherocytes (decreased deformability) → erythrostasis due to splenic trapping → phagocytosis

What are symptoms of Hereditary Spherocytosis?

• anemia

• jaundice

• splenomegaly

• in infancy, childhood, adulthood

What lab findings indicate Hereditary Spherocytosis?

• hallmark → spherocytes

• polychromasia

• reticulocytes

• ↑ MCHC and RDW

• ↑ osmotic fragility

What is used to treat Hereditary Spherocytosis?

• Splenectomy

What is the etiology of Hereditary Xerocytosis?

• rare autosomal dominant

• defect in cation permeability of RBC

  • effects hydration

• K+ leak

  • RBC dehydrated

What are symptoms of Hereditary Xerocytosis?

• mild - mod compensated anemia

• splenomegaly

• may show iron overload

What lab findings indicate Hereditary Xerocytosis

• ↑ MCHC - dehydration

• mild ↑ MCV

• target cells

• burr cells

• puddled cells

• ↓ osmotic fragility

What treatment is used for Hereditary Xerocytosis?

• None needed

What is the etiology of Hereditary pyropoikilocytosis?

• a and B disorder

• microspherocytes and micropokilocytosis

• fragments

• few elliptocytes

What lab findings indicate Hereditary pyropoikilocytosis?

• extreme poikilocytosis

• many fragmented RBC

• microspherocytes

• low fluorescence with eosin 5 ‘ maleimide

• MCV: 50 - 65 fl

• thermal sensitivity

  • RBC fragment 41 - 45 C

What is the treatment for Hereditary pyropoikilocytosis?

• splenectomy

• RBC transfusions to treat anemia

What is the etiology of Hereditary Elliptocytosis?

• heterogenous group of hemolytic anemias

• presence of elliptical (oval) RBCs

• more common in Africa and Mediterranean

• majority are autosomal dominant

• abnormality is in membrane skeleton - spectrin / protein

What are the groups of Hereditary Elliptocytosis?

• Common HE - most prevalent

• SE Asia Ovalocytosis

• Hereditary pyropoikilocytosis

What clinical findings indicate Hereditary Elliptocytosis?

• most are asymptomatic

• can have mild compensated hemolysis

• MCV: norm / ↑

• reticulocytosis

• elliptocytosis, not oval, like cigars

• norm / ↑ osmotic fragility

What is used to treat Hereditary Elliptocytosis?

• Mild - none

• Severe (HPP)

  • splenectomy

  • RBC transfusions to treat anemia

What mutations are associated with Hereditary Elliptocytosis?

• alpha spectrin (65% of cases)

• Beta spectrin (30% of cases)

• protein 4.1 (5% of cases)

• description of spectrin → destabilizes cytoskeleton

• horizontal defect

Describe SE Asian Ovalocytosis.

• seen in SE Asian population

• has spoon shaped ovalocytes

• resistant to malaria

• has two distinct ridges / transverse bars

What is the etiology of a G6PD deficiency

• oxidative damage to RBCs

  • can NOT produce enough NADPH to keep glutathione reduced

• no glutathione = RBC can not detoxify H2O2

• leads to: hemoglobin oxidation / RBC destruction

What morphological findings indicate a G6PD deficiency?

• normocytic / normochromic anemia

• reticulocytosis

• anisocytosis

• poikilocytosis

• spherocytosis

• Helmet Cells

• Heinz Bodies

What do these lab findings indicate?

• Hemoglobinuria and Jaundice

• Anemia 

• Hyperbilirubinemia (neonatal)

  • Kernicterus > 18 mg/dl

  • Brain damage > 25 mg/dl 

• ↑ LDH

• Dark urine 

• Splenomegaly 

• Chills, fever, headache, nausea, vomiting, back pain 

• Asymptomatic until exposed to triggering mechanism 

  • fava beans, drugs, infections

GP6PD deficiency

What is used to treat G6PD deficiency?

• discontinue implicated drugs

• RBC transfusion

What is the etiology of Babesia?

• tick transmitted disease: B. microti

• humans are incidental host

• can also be transmitted from transfusing RBC from asymptomatic donors

What are symptoms of Babesia?

• 1-9 week incubation period

• asymptomatic, fever, chills, headache, sweats, nausea, fatigue

• jaundice, splenomegaly, hepatomegaly

• history of tick infested area

What lab findings indicate Babesia?

• low Hgb

• ↑ retic count

• ↓ serum haptoglobin

• bilirubinemia

• Leukopenia, throkbocytopenia, hemoglobinuria, proteinuria

What is used to treat babesia?

• Clindamycin

• Quinine