RBC pathology

polycthemia

thrombosis (high RBC)

male hemoglobin adn female

• male: 13.8 - 17.2

• Female: 12.1-15.1

hematocrit

Fraction or % of blood that is packed with RBCs

• males; 40-52%

• Female; 38-48%

hematopoiesis

• production of new blood cells

• stem cell in bone marrow called hemocytoblasts

• growth factors stim differentiation into

  • RBC

  • WBC

  • platelets

Erythopoiesis

• lose nucleus and the reticulocyte is released into blood

• persist foe 24 hours, loss of cytoplasmic RNA, mature RBC

• remains in circulation for 110-120 days before removed by macrophages in spleen

homeostatic control of RBC in blood

• decreased blood oxygen (from low RBC) → kidney makes erytopoietin → stims RBC production to get to set point

fate of old damaged RBC

• globin → amino acids

• heme → iron recycle, converted into biliruibin (yellow pigment)

two main hemolysis (hemolytic anemia)_

• Red cell membrane is damaged and cell bursts in blood vessels: intravascular hemolysis (hemoglobinemia, hemoglobinuria, loss of iron)

  • mechanical forces

  • toxins

• Red cell defective and phagocytized by macrophages in spleen

Extravascular hemolysis consequences

too many cells trapped in spleen:

• splenomegaly

• hemolytic anemia

• hyperbiliruibinemia

  • deposits in tissue → jaundice

  • to liver: high level in bile → gallstones

hereditary spherocytosis pathogensis

• autosomal dominant

• mutation in cytoskeletal proteins

  • Band 3

  • ankyrin

  • spectrin

• the link between cytoskeleton and bilayer weakens

  • unsupported areas of lipid bilayer lost “blebs”

  • lose more membrane than cytosol

  • Decrease in surface to volumer ratio

• trapped and destoryed in spleen

  • smaller

  • spherical

  • dont deform

• yes anemic

• yes cna be huge

• elevated

• yes

• yes

• elevated

• subclinical to severe

how can you tell if someone has hereditary spherocytosis

• do a peripheral blood smear to look for spherocytes

  • no zone of central pallor

  • variation in size with many small RBC

hereditary spherocytosis treatment

• splenectomy

• +

  • reduce RBC destruction and correct anemia

• -

  • risk of infection (immune organ)

pathogenesis of sickle cell anemia

• point mutation in gene for B globin chain of hemoglobin

  • sickle:

    • 2 mutated B globin,

    • 2 alpha globin (hemoglobin S)

  • normal

    • 2B globin

    • heme (fe)

    • hemoglobin A (HbA): 96

genetics of sickle cell anemia

• homozygous: both mutated alleles

  • no HbA

  • mostly HbS

  • disease

• hetero

  • 60% HbA

  • 40% HbS

• inhereited in recessive pattern

reversible sickling

• healthy: oxyhemoglobin S → biconcave

• Deoxyhemoglobin S in RBC → HbS polymerizes → reversible sickling

factors affect sickling of RBC

• oxygen tnesion

• presence of other forms of hemoglobin (HbF (fetal) prevent polymerization: 5-6 months to switch from HbF to HbA

• conc of HbS in RBC

  • dehydration promotes sickling

• Sluggish blood flow

  • longer time in capillaries → more time to sickle in microvasculature

  • esp spleen and bone marrow, and with inflammation

Consequences of sickle

• chronic hemolytic anemia (mod to severe) → both extra and intravascular → 20 day lifespan of RBC

• Episdoic pain crises (vasoocclusive crisis) associated with ischemic tissue damage

  • spontaneosuly

  • precipitating stimulus →

    • slows down flow

    • increase conc of HbS

signs/sympt of sickle cell anemia

• fatigue palllor

• low hemoglobin levels

• elevated erythropoitein levels

• elevated reiculocytees

• elevated bilirubin → jaundice and gallstones

how does thalassemia differ from sickel cell anemia

• thess

  • Mutation that causes the amount of a globin or B globin chain to bre reduced or absent

  • minor to intermed to major

• sickle

  • mutation in B globin causing HbS

  • Sc trait

  • Sc anemia

pathogeneis of anemia from B thalassemia

• reduced synthesis of B globin

  • inadequate HbA formation

    • RBC less hemoglobin

  • Excess unpaired a globin in erythroid percurors causes hemoglobin to aggregate and precipitate → membrane damage

• extravasvular hemolysis and apopotsis of precursors in bone marrow

b thalassemia peripheral blood smer

pale cells (hypochromic) small cells, microcystic?

general manifestations of b thalasassemia anemia

• reduced hemoglobin → less O2

• tonf of erythopoitein

• hepatomegaly, splenomegaly, skeleton abornamliites

  • skeletal: marrow hyperplasia and expansion

  • frontal bossing

b thalassemia treatment options

1. bone marrow transplant

2. blood transfusion thruout life

   1. req for surival

   2. iron overload and failure and death: prevented by ion chelators (excrete via kidney)

B thalassemia minor vs major

• minor:

  • target cells

  • mild microcytic

  • hypochromic anemia

  • asymptomatic

Anemias of diminished erythhropoiesis

• inadequate nutrinets

  • iron

  • folic acid

  • vitamin B12

• Bone marrow failure (aplastic anemia)

• systemic inflammation (chronic disease)

• bone marrow infiltration by tumor or inflammatory cells

peripheral blood smear of iron deficient anemia

hypochromatic, microcytic due to decreased hb production

main causes of iron deficiency

• Chronic blood loss

  • GI tract

  • uterus

• Increased requirement

  • pregnancy

• inadequate iron intake

  • dietary insufficiency is not common in uS

  • general intestinal malabsorption

folate and vitamin B12 anemia causes ___? what is its pathogenesis

• megaloblastic anemia

  • big cells

1. Erythroid progenitor

2. Lacks either folate or B12

3. Insufficent DNA synthesis and cel division

4. Unimpaired RNA and protein synthesis

5. macro-ovalocytes

megaloblastic anemia blood smear

• hypersegmented nuclei

• large hyperchromic cells

what causes glossitis: what is it?

• nutritional deficiencies, such as folic acid, vitamin B12, iron deificency

• inflammation and atrophy of lingual papillae

vitamin B12 deficiency consequncies

• nerve demyelination in spinal cord

  • numbness. tingling, burning in hands and feet

  • loss of position sense

  • unsteady gait

  • megaloblastic anemia reversible, neurological problems irreversible

main causes of folic acid deficiecy

• decreased diet intake

  • destoryed by cooking

  • stores only last few weeks

• chronic alcoholism or liver diseae

  • folate stored in liver

• increased req (preg)

• MAlabsorption (celiac)

• drug induced

vitamin B12 deficiency caues

• Not diet unless vegetarian or vegan

  • meat, fish, eggs

• malabsorption

  • loss of intrinisc factor

    • pernicious anemia (autoimmune to parietal cells)

  • loss of acid and pepsin to release vitamin B12

  • loss of IF: absorption