disorders of RBC (PATHO BEFORE CLASS 2)

Red blood cells

Erythrocyte

Contain hemoglobin

Oxygen transport

Polycythemia

Overproliferation of all blood cells in bone marrow

Less common than anemia

Anemia

Major pathophysiological condition of RBCs

Insufficient oxygen delivery to RBC issue

Increased risk of some forms in certain races/ethnic groups

Erythropoiesis

Synthesis of RBCs

Erythropoietin (EPO)

Released from kidneys

Stimulate RBC formation

Pluripotent stem cells

In bone marrow

RBCs, WBCs, platelets

Reticulocyte

Immature RBC

Reticulocytosis

Increased reticulocyte levels

Indicate increased RBC synthesis

Mature RBC

Has no nucleus

Average lifespan—120 days

Spleen

Removes aged RBCs

Erythrocyte Synthesis in states of hypoxia

• 
  

• Kidney releases erythropoietin (EPO)

  • EPO simulates bone marrow to produce RBCs

• Increased RBCs to compensate for the hypoxia

RBC formation 

Factors needed:

Protein, iron, vitamin B₁₂, folic acid

RBC breakdown

Some components recycled

Hemoglobin

Oxygen carrying component of RBC

Hemoglobin breakdown

Hemoglobin breaks down to heme plus globin

Globin breaks down into porphyrin

Porphyrin breaks down to biliverdin

Bilirubin

Formed from biliverdin

Byproduct of RBC breakdown

Hyperbilirubinemia

Bilirubin accumulates in bloodstream

Jaundice

Yellowing of skin and sclera

Bilirubin accumulation 

Hemoglobin def

• High oxygen affinity

• Four polypeptide chains

  • Two alpha and two beta

  • Contain iron for oxygen binding

• Hemoglobin types

  • Normal hemoglobin (Hgb A)

  • Fetal hemoglobin (Hgb F)

  • Hemoglobinopathy: Abnormal Hgb

    • Example: Sickle cell anemia (Hgb S)

Iron Metabolism

• Required for RBC formation

  • Iron from RBC’s is recycled

• Transferrin

• Transports iron

• Total iron binding capacity (TIBC)

• 
  

• Elevates when iron levels are low 

• More binding spaces available

• Ferritin complexes:

• store iron

  • Present in all cells, but most common in bone marrow, liver, spleen

Oxyhemoglobin Dissociation Curve

• PO₂ and O₂ saturation of Hgb (O₂ sat)

  • Low O₂ sat compromises O₂ delivery

• Influences on dissociation curve:

• shift to right

• 
  

• decreased oxygen affinity

  • Increased CO₂, decrease pH (Bohr effect), increased 2,3 diphosphoglycerate (2,3 DPG), fever

• Influences on dissociation curve:

• shift to the left

• 
  

• increased affinity for oxygen

  • Opposite conditions as above

• Carbon monoxide (CO)

• 
  

• High affinity for Hgb

Blood Types

• Agglutinogens

• Specific RBC antigens

  • Two types: A and B

  • Determine blood type 

    • A, B, AB, O

• Rh factor: D antigen

  • Positive or negative

  • Rh+ or Rh−

    • A+, AB+, A−, etc.

• Antibodies

• produced against blood antigens not present

  • Example: 

    • Type A blood has anti-B antibodies

    • Type B blood has anti-A antibodies

universal blood type

• 
  

• Donor: Type O

• Recipient: Type AB

• Transfusions: blood type

• 
  

• Recipient’s antibodies can attack donor cells

• Type and crossmatch

• antibodies impronat

Hemoglobin (Hgb)

Amount of Hgb in blood (g/dL)

Males: 13–18 g/dL

Females: 12–16 g/dL

Hematocrit (Hct)

Percentage of whole blood consisting of RBCs

Males: 45%–52%

Females: 37%–48%

Total RBCs

Number of RBCs per cubic milliliter

Males 4.5–5.5 × 10⁶

females: 4.0–4.9 × 10⁶

Reticulocytes

Immature RBCs

1% of total RBCs

Assessment of RBCs: size

• Macrocytic (megaloblastic), normocytic, microcytic

  • Mean corpuscular volume (MCV)

Assesment of RBCS color

• Hyperchromic, normochromic, hypochromic

  • Mean corpuscular hemoglobin (MCH)

    • Average amount of Hgb in average RBC

• NCNC: normochromic, normocytic

Anemia

• Possible etiologies

  • Deficiencies: Iron, vitamin B₁₂, folic acid

  • Blood loss: Chronic and acute

  • Hemoglobinopathies

  • Medications

  • Hemolysis

• Different etiologies present with different diagnostic findings

Anemia Signs and Symptom

• May be asymptomatic

• Excessive fatigue

• GI tract blood loss: Melena, hematochezia

• Heavy menstrual periods (menorrhagia)

• Pale complexion

• Tachycardia

• Jaundice

• Splenomegaly

• Nutritional anemias can cause glossitis, cheilitis, koilonychia, or pica

Anemia Diagnosis and Treatment

• Diagnosis

  • Complete blood count: Hb, Hct, RBC count

  • Peripheral blood smear: size, shape, color of RBCs

  • Bone marrow aspiration

  • Echocardiogram/electrocardiogram

  • Nutritional status assessment

• Treatment

  • Varies based on cause

Anemia Caused by Decrease in RBC Mass

• Adult total blood volume: 5 liters

• Can lose 500 mL of blood without serious effects

• Loss of 1,000 mL or more:

  • Serious adverse effects 

  • Hypovolemic shock

  • Cerebral hypoperfusion

Anemia of Acute Blood Loss

• Trauma, hemorrhage, clotting disorder

• Diagnosis

  • NCNC with reticulocytosis

  • Evaluate platelet levels and clotting times

  • FOBT to determine GI blood loss

anemia of acute blood loss treatment

• 
  

• For blood loss, establish hemostasis and fluid volume

  • IV: normal saline

  • Blood transfusion

Amount of Blood Loss <15%

Orthostatic hypotension and anxiety

Amount of Blood Loss 15-30%

SNS activity, increased HR

Activation of RAAS

Release of ADH (decrease urine output)

Restlessness and change in consciousness

Amount of Blood Loss 30-40%

HR >120 bpm

Hypotension

Urine output 5–15 mL/hr

Amount of Blood Loss >40%

Severe hypotension

Decreased consciousness

HR >140 bpm

No urine output

Anemia Caused by Chronic Blood Loss causes

• 
  

• GI bleeding

• Menstrual blood loss 

• Medications

  • NSAIDs may lead to GI bleeding

Anemia Caused by Chronic Blood Loss ss

• 
  

• Blood loss is slow

• Patient may report no noticeable changes

Anemia Caused by Chronic Blood Loss  diagnosis

• 
  

• Iron assessment: 

  • Low iron, low ferritin, increased TIBC

• Microcytic and hypochromic anemia

• Low Hgb and Hct

Anemia Caused by Chronic Blood Loss  treatmemt

• 
  

• Remedy reason for blood loss

• Replace iron: oral ferrous sulfate

Hemolytic Anemias

• Erythrocyte destruction: Outpaces replacement

Hemolytic Anemias causes

• 
  

• Hemoglobinopathies

  • Inherited disorder of Hgb

• Autoimmune disorders

  • Warm (IgG) and cold (IgM) agglutinin syndrome

• Alloimmune hemolysis

  • Blood transfusion reactions

  • Hemolytic disease of the newborn (HDN)

• 
  

• Hereditary spherocytosis

• Lead poisoning

Hemolytic Anemias  ss

• 
  

• Typical anemia signs PLUS jaundice, dark urine (urobilinogen), enlarged spleen due to elevated RBC breakdown

Hemolytic Anemias Diagnosis

• 
  

• Elevated reticulocytes to replace lost cells, peripheral smear will show misshapen and damaged RBCs

Hemolytic Anemias treatment

• 
  

• Depends on underlying causes

Hemoglobinopathy

• Inherited disorder

  • Abnormal structure of the Hgb molecule

    • Cannot carry oxygen efficiently

  • Leads to destruction of RBC

• Examples:

  • Sickle cell anemia (SCA)

  • Thalassemia

Sickle Cell Anemia (SCA)

• Autosomal hemoglobinopathy

• Homozygous and heterozygous forms (HbS)

  • Homozygous form more severe

  • Carrier state

  • Distorts shape of RBC (exposure to hypoxia, dehydration, stress)

  • Signs do not appear until fetal Hgb levels decline

• Malaria: 

  • SCA provides increased resistance to malaria

  • Genetic expression has remained high

Sickle Cell Anemia (SCA) Peripheral blood smear

• 
  

• RBC misshapen, sickle-cell appearance

Sickle Cell Anemia (SCA) Abnormal RBCs 

• 
  

• Lifespan of 10 to 20 days

• Reticulocytosis

Sickle Cell Anemia (SCA)  vaso-occlusive crises

• Misshaped RBC

• Lodge in capillaries

• Causing tissue hypoxia

• Very painful

• Chronic damage to liver, spleen, kidneys, and eyes

  • Spleen may become damaged, requiring removal

Sickle Cell Anemia (SCA)  clinical presentation

• 
  

• Typical anemia signs, hyperbilirubinemia and enlarge spleen may be present 

• Vaso-occlusive crisis

sickle cell anemia diagnosis

• Electrophoresis revealing HbS

Sickle Cell Anemia (SCA) treatment

• 
  

• Avoid triggers of vaso-occlusive crises

• Folic acid supplement to assist in RBC synthesis

• Blood transfusions to replace lost cells (watch that iron levels do not elevate too much)

• Bone marrow transplant

Thalassemia

• Autosomal recessive hemoglobinopathy

  • Major form: homozygous

  • Minor form: heterozygous

• Genetic defect

  • Thalassemia alpha: alpha chain of Hgb affected

  • Thalassemia beta: beta chain of Hgb affected

Thalassemia  presentation

• 
  

• Typical anemia signs

• Bone pain may be present

  • Bone marrow replaces lost RBCs

• Hyperbilirubinemia and jaundice

• Splenomegaly

• Heinz bodies may be present

  • Pathognomonic for thalassemia

  • Collection of polypeptide chain in RBCs

Thalassemia children

• 
  

• “Chipmunk” cheeks 

• “Hair-on-end” appearance of skull bones

Thalassemia Diagnosis genetic testing

• 
  

• Exact nucleotide sequence 

• Deletions, duplications 

• Chromosomal rearrangements

• Prenatal testing, and genetic counselling   

Thalassemia Diagnosis radiographic results

• 
  

• Thinning of cortical bone 

• Resorption of cancellous bone

Thalassemia Treatment

• Transfusions

• Infection prevention

• Folic acid supplementation

• Gene therapy and gene editing under consideration 

• Luspatercept

  • Improves RBC maturation 

  • Approved for with transfusion-dependent beta thalassemia (November 2019)

Hereditary Spherocytosis

autosomoal

abnomral membrane proteins in rbc

spherical shpe to rbc, increased fragility, damage cells gather in spleen

ss- jaundice, bilirubin gallstones, aplastic anemmia

treatment-blod transfusions, splenectomy, folic acid supplemenation

Blood Transfusion Reactions

• Known as hemolytic transfusion reactions

  • Recipient blood-type antibodies attack transfused cells

• Type and crossmatch

  • Mandatory that two clinicians double check donor-recipient blood types

• If transfusion reaction suspected, stop transfusion

Blood Transfusion Reactions  presnetaion adn manifestations

• 
  

• Nonhemolytic febrile reactions and mild allergies

• Anaphylactic reactions

• Manifestations

  • Fever, chills, flushing, burning at IV line, joint pain, tachycardia

  • Severe cases

    • Hypotension, oozing from the IV site, diffuse bleeding, oliguria, shock, and renal failure

Hemolytic Disease of the Newborn (HDN) abo antigens

IgM antibodies cannot cross placenta

Mother can carry pregnancy without problem

During delivery, blood may mix

Hemolysis of infant RBCs, mild hyperbilirubinemia

Sunlight/phototherapy for infant

Hemolytic Disease of the Newborn (HDN) Rh antigens

Rh-negative mother, Rh-positive fetus

Erythroblastosis fetalis

Rh antibodies from mother can cross placenta

Rh positive cells of fetus attacked by antibodies

Hemolysis, hyperbilirubinemia in infant

RhoGAM given to mother to prevent antibodies

Anemia Due to Lead Poisoning

• Lead

  • Impairs hemoglobin synthesis

  • Triggers hemolysis

  • Toxic to neurological system of children

• May cause iron deficiency anemia

• Blood test to check for lead levels

• Chelation therapy

RBC Maturation Defects

• Typical signs of anemia

  • Specific signs and symptoms related to etiology

• Key factors:

  • Iron deficiency

  • Vitamin B₁₂ deficiency

  • Folic acid deficiency

Iron Deficiency Anemia

women most common

most at riskp womens and childberaing age, infants and childrens, elderly, vegaterians, gi bleeding

etiology-menorrhagia, gi bleed, inadequate iron intake

ss-hair loss, glossitis, nial chnages, pica

Iron Deficiency Anemia  diagnosins treatment

• Diagnosis

  • CBC

  • Peripheral blood smear

    • Pale (hypochromic) and small (microcytic)

  • Serum iron and ferritin are decreased

  • FOBT should be done to rule out GI bleed

• Treatment

  • Oral ferrous sulfate

  • Correction of underlying etiology

Vitamin B₁₂ Deficiency

uknown vit b12 defincit

perniciois anemia0disruptists intristic factor needed for b12 absoprion-common cuase anemia worldwide

needed for rbc synthesis, dna synthesis, myelin sheath formation

mlanutrtion, vegan diet, elderly, food cobalamin malaabsoprtion syndrome, achlorhdria at risk and bariastric surgery

Vitamin B₁₂ Deficiency needed for

•  folic acid metabolism and RBC DNA 

  • Megaloblastic anemia

• Neurological system

  • Typical signs of anemia along with glossitis, numbness and tingling, unsteady gate

• Diagnosis

  • CBC, peripheral blood smear reveals large cells

  • Folate, homocysteine, and methylmalonic acid levels should be examined

Vitamin B₁₂ Deficiency treatment

• 
  

• Address underlying etiology

• Intramuscular B₁₂ injections may be needed

Folic Acid Deficiency

• At risk: pregnant and lactating women, alcohol abusers, elderly, celiac disease sufferers

• Megaloblastic anemia

  • Folate along with vitamin B₁₂ needed for RBC DNA synthesis

• Other needs

  • Decreased incidence of spina bifida

  • Breaks down homocysteine

    • High homocysteine associated with increased risk of CVD

Folic Acid Deficiency  symtom trearment

• Patients may be asymptomatic 

• Connection with vitamin B₁₂    

  • Adequate B₁₂ needed for successful folate metabolism

  • Determine levels of both

• Treatment

  • Oral replacement of folic acid

Lack of Bone Marrow Production of RBCs

• Erythropoietin (EPO) lack

  • Usually due to kidney failure

  • Hypothyroidism may also decrease EPO

  • Recombinant EPO can be given

Aplastic Anemia

rare

bone marrow fails, pancytopenia

infection hepatitis, hiv, ebv, radaition, chemicals,, certian drugs, immune disease genetic mutation all at risk

ss- devolop abruptly or gradully, anemia, increased bleeding and bruising, increased infection risk

Aplastic Anemia

• Diagnosis

• 
  

• CBC: pancytopenia

• Bone marrow: severe hypocellularity with predominance of fat cells

• Genetic testing

Aplastic Anemia treatment

• 
  

• Blood transfusions

• Broad-spectrum antibiotics to control infection

• Bone marrow transplant

• Bone marrow stimulating agents

Anemia of Chronic Disease (ACD)

• 
  

• Decreased RBC survival time

• Blunted erythropoietic response

• Impaired iron metabolism

• Signs and symptoms of anemia are present

• Transfusions not recommended

• EPO administration is preferred treatment

  • Higher than normal levels may be needed

Primary Polycythemia

• AKA: polycythemia vera

• Hyperproliferation of all blood cells

  • Increased clot risk

  • CBC may show HCt >60%

• Etiology unknown, may be chromosomal abnormality

• Rare

• EPO level is low

Secondary Polycythemia

• AKA: erythrocytosis

• More common than primary form

  • Caused by prolonged hypoxia, i.e., COPD

  • Correct underlying hypoxia will reverse condition

• Signs and symptoms develop slowly

  • Spleen may enlarge

• EPO levels are HIGH

Reticulocytes

Indicator of bone marrow activity

High reticulocyte count indicates elevated RBC formation

Spleen

“Graveyard of RBCs” 

Also organ of immunity

Splenomegaly occurs with large RBC breakdown

Medications

Drugs known to trigger hemolytic anemia: cephalosporins, quinidine, penicillins, levodopa, methyldopa, and NSAIDs

Splenectomy

Causes immunodeficiency

Renal failure

EPO used to stimulate RBC production and correct anemia

• Carbon monoxide

• 
  

• Greater affinity than oxygen for hemoglobin

• Displaces oxygen from hemoglobin

• Iron deficiency 

• 
  

• In adult male, suspect GI blood loss until ruled out

• Folic acid deficiency

• 
  

• Must exclude vitamin B₁₂ deficiency