Patho: Disorders of red blood cells, HEMATOLOGIC SYSTEM

The Red Blood Cell: Overview 

• Function of the RBC: Carry and transport oxygen to the tissues of the body 

• Too few RBCs: Anemia 

• Too many RBCs: Polycythemia 

• Review normal RBC count: 4.2-6.1 cells/mcL 

• Normal Hemoglobin (Hgb): ____12-16 g/dL__

• Normal Hematocrit (Hct): _____3x Hgb____ 

• “H&H” = hemoglobin & hematocrit 

• Hemoglobin Synthesis 

  • Iron (Fe) is necessary 

What is the function of the RBC

Carry and transport oxygen to the tissues of the body 

Too few RBCs=

anemia

too many RBCs=

polycythemia

What is the normal RBC count?

4.2-6.1 cells/mcL 

What is the normal Hemoglobin (Hgb):

12-16 g/dL

Normal Hematocrit (Hct):

3x Hgb

“H&H” =

hemoglobin & hematocrit

Red Blood Cell Production 

• Erythropoiesis- production of RBCs; begins in bone marrow and completed in blood or spleen 

• Erythropoietin- hormone released by the kidneys in response to tissue hypoxia. Stimulates bone marrow to produce more RBCs 

• Requires folic acid and B12 to mature 

• Red Blood Cell Destruction 

  • RBC lifespan is ~ 120 days 

  • Rate of destruction = rate of production 

  • Destruction is facilitated by the spleen, liver, bone marrow, and lymph nodes 

  • Amino acids and iron from the heme units are salvaged and reused 

  • Bulk of the heme unit is converted into bilirubin and secreted in bile or excreted in the feces or urine 

    • Unconjugated bilirubin (insoluble)- “bad!” 

      • Excessive RBC destruction leads to accumulation of unconjugated bilirubin in blood- results in jaundice 

    • Conjugated bilirubin (water soluble)- okay! 

What is the production of RBCs; begins in bone marrow and completed in blood or spleen 

Erythropoiesis

What is the hormone released by the kidneys in response to tissue hypoxia. Stimulates bone marrow to produce more RBCs

Erythropoietin

Red blood cell production requres what to mature?

folic acid, B12, and iron

Red blood cell destruction

• RBC lifespan is ~ 120 days 

• Rate of destruction = rate of production 

• Destruction is facilitated by the spleen, liver, bone marrow, and lymph nodes 

• Amino acids and iron from the heme units are salvaged and reused 

• Bulk of the heme unit is converted into bilirubin and secreted in bile or excreted in the feces or urine 

  • Unconjugated bilirubin (insoluble)- “bad!” 

    • Excessive RBC destruction leads to accumulation of unconjugated bilirubin in blood- results in jaundice 

  • Conjugated bilirubin (water soluble)- okay! 

What is the lifespan of a RBC

120 days

Unconjugated bilirubin (insoluble)-

“bad”

• Excessive RBC destruction leads to accumulation of unconjugated bilirubin in blood- results in jaundice 

Conjugated bilirubin (water soluble)-

“okay”

Red Blood Cell Metabolism and Hemoglobin Oxidation – Brief Overview 

• Oxygen binds to hemoglobin for transport to the cells 

• Oxyhemoglobin- Hemoglobin bound with oxygen. 

  • 95%-98% saturated with O2 in arterial blood 

  • 75% saturated in venous blood. 

 

• Binding Affinity of Hemoglobin for Oxygen 

  • The hemoglobin molecule should bind to the oxygen molecule. 

  • The hemoglobin molecule should release it as needed to the tissues/cells.  

  • Affinity- Hemoglobin’s ability to bind and hold onto oxygen. 

    • Increased affinity = Hemoglobin binds more readily to oxygen (holds on tightly) 

    • Decreased affinity = Hemoglobin releases the oxygen to the cells more easily (easily lets it go) 

• Factors affecting affinity: pH, CO2 levels, body temperature, oxygen levels 

Anemia overview:

• Overview 

  • Anemia = abnormally low hemoglobin levels, RBC levels, or both 

  • Causes: 

    • Excessive blood loss 

    • Destruction of RBCs 

    • Deficient RBC production 

 

• General manifestations of all anemias (depend on age, severity, and rapidity of development): 

  • Symptoms of tissue hypoxia 

  • Fatigue, very tired  

  • Headache, because youre not getting good perfusion in the brain  

  • Chest pain, heart isn’t getting good perfusion 

  • Dizziness  

  • Tachycardia, fast heartrate because heart is trying to make up for the low perfusion everywhere 

  • Pallor(pale skin) or cyanosis(blueish discoloration) 

• Small decreases in H&H are usually tolerated 

• Remember: Tissue hypoxia is the main stimulus for RBC production. 

 

What is being described?

• abnormally low hemoglobin levels, RBC levels, or both 

anemia

What are causes of anemia?

1. Excessive blood loss 

2. Destruction of RBCs 

3. Deficient RBC production 

General manifestations of all anemias (depend on age, severity, and rapidity of development): 

• Symptoms of tissue hypoxia 

  • Fatigue, very tired  

  • Headache, because youre not getting good perfusion in the brain  

  • Chest pain, heart isn’t getting good perfusion 

  • Dizziness  

  • Tachycardia, fast heartrate because heart is trying to make up for the low perfusion everywhere 

  • Pallor(pale skin) or cyanosis(blueish discoloration)

What is the the main stimulus for RBC production. 

tissue hypoxia

What is being described here?

• Excessive blood loss (acute or chronic, (slowly bleeding over a long period of time)) 

• RBCs are normal in size and color 

• Result: hypoxia stimulates the release of erythropoietin à stimulates RBC production from bone marrow 

• Potential causes: 

  • Trauma  

 

blood loss anemia

What is being described here?

• Excessive destruction of RBCs 

• RBCs normal size and color 

• Inherited hemolytic anemias

  • Sickle Cell Disease  

• Acquired Hemolytic Anemias 

 

hemolytic anemias

What kind of anemia is this?

• Autosomal recessive,  (two people that are carriers would have to have a child, in order for that child to have the disease) 

• Results in “sickling” of the Hemoglobin S (HbS) molecule 

• Molecule changes the shape of the RBC to a sickled shape when the person experiences cold, stress, physical exertion, infection, illness- dehydration, acidosis, hypoxia 

• Abnormally shaped cells 1) cannot efficiently carry oxygen; 2) clump together causing blood clots(leads to decreased perfusion and tissue injury) 

• RBCs have shorter lifespan 

• Causes severe pain and tissue ischemia 

sickle cell disease

manifestations of sickle cell crisis

• pain in abdomen

• chest, joints

• bone infarcts

• joint damage

• skin ulcers

• stroke

• retinal infarcts

• occlusion in vessels of lungs

Acquired Hemolytic Anemias 

May be caused by drugs, chemicals, toxins, venoms, or infections such as malaria that destroy cell membranes 

Anemias of Deficient Red Blood Cell Production 

1. Iron Deficiency 

• Iron is necessary to synthesize new RBCs 

• Causes: 

  • Inadequate dietary intake (ex: vegetarians) 

  • Increased iron demands (ex: pregnancy) 

  • Excessive iron loss

• Manifestations: 

  • Similar to all anemias and... 

  • Brittle hair/nails 

  • Smooth tongue 

  • Spoon-shaped fingernails 

  • Pica 

 

 

(2)Megaloblastic Anemias 

• (1)Vitamin B12 Deficiency Anemia 

  • Vitamin B12 needed for DNA synthesis in RBC 

  • Due to inadequate dietary intake 

  • Or due to lack of intrinsic factor in the stomach 

    • Pernicious anemia- possibly autoimmune caused by atrophic gastritis 

    • Inability to produce intrinsic factor to absorb B12 

    • Requires lifetime vitamin B12 replacement with injection 

  • Neurologic symptoms can develop if left untreated 

    • Paresthesia, numbness or tingly feeling in the hands and feet

    
    

  • (2)Folic Acid Deficiency Anemia 

    • Required for DNA synthesis 

    • Causes: Malnutrition, inadequate dietary intake 

    • Increased need for folic acid during pregnancy 

      • Recommended that women of child-bearing age take 400 mg of folic acid daily 

 

3. Aplastic Anemia 

   1. Also called pancytopenia 

   2. Reduction of all types of blood cells: RBCs, WBCs, and platelets 

   3. Causes: Radiation, chemicals, toxins, many infections (especially viral) 

   4. Manifestations: signs & symptoms related to reductions in all blood cells 

 

4. Chronic Disease Anemias 

   1. Anemias due to underlying disease 

   2. Causes: 

      1. Chronic infections 

      2. Inflammation 

      3. Cancer 

      4. Chronic renal failure 

         1. People with this are almost always anemic because their kidneys are not producing erythropoietin  

What is iron deficiency anemia?

• Iron is necessary to synthesize new RBCs 

  • Causes: 

    • Inadequate dietary intake (ex: vegetarians) 

    • Increased iron demands (ex: pregnancy) 

    • Excessive iron loss 

    
    

• Manifestations: 

  • Similar to all anemias and... 

  • Brittle hair/nails 

  • Smooth tongue 

  • Spoon-shaped fingernails 

  • Pica

Causes of iron defiency anemia:

• Inadequate dietary intake (ex: vegetarians) 

• Increased iron demands (ex: pregnancy) 

• Excessive iron loss 

Manefestations of iron deficeincy anemia

• Brittle hair/nails 

• Smooth tongue 

• Spoon-shaped fingernails 

• Pica 

What are Megaloblastic Anemias 

• Vitamin B12 Deficiency Anemia 

• Folic Acid Deficiency Anemia 

What kind of anemia is being described?

• Vitamin B12 needed for DNA synthesis in RBC 

• Due to inadequate dietary intake 

• Or due to lack of intrinsic factor in the stomach 

  • Pernicious anemia- possibly autoimmune caused by atrophic gastritis 

  • Inability to produce intrinsic factor to absorb B12 

  • Requires lifetime vitamin B12 replacement with injection 

  • Neurologic symptoms can develop if left untreated 

    • Paresthesia, numbness or tingly feeling in the hands and feet  

Vitamin B12 Deficiency Anemia (megoblastic anemia)

What is Pernicious anemia?

• B12 anemia caused by lack of intrinsic factor, preventing B12 absorption

• caused by autoimmune disease atrophic gastritis, or gastrectomy

• treated with lifelong B12 injections

What anemia is being described here?

• Required for DNA synthesis 

• Causes: Malnutrition, inadequate dietary intake 

• Increased need for folic acid during pregnancy 

  • Recommended that women of child-bearing age take 400 mg of folic acid daily 

Folic Acid Deficiency Anemia 

What is aplastic anemia?

• Also called pancytopenia 

• Reduction of all types of blood cells: RBCs, WBCs, and platelets 

• Causes: Radiation, chemicals, toxins, many infections (especially viral) 

• Manifestations: signs & symptoms related to reductions in all blood cells 

Causes of aplastic anemia

• Radiation, chemicals, toxins, many infections (especially viral) 

Manefestations of aplastic anemia:

signs & symptoms related to reductions in all blood cells 

What are chronic diease anemias?

• Anemias due to underlying disease 

• Causes: 

  • Chronic infections 

  • Inflammation 

  • Cancer 

  • Chronic renal failure 

    • People with this are almost always anemic because their kidneys are not producing erythropoietin  

ABO Blood groups

• A 

• B 

• AB+: universal recipient  

• O: O- is the universal donor  

Universal Blood Recipient

Blood type AB + (positive)

Universal Blood Donor

Blood type O - (negative)

Blood compatibility chart:

image of Blood compatibility chart:

Rh types

• positive

• negative

Blood Transfusion Reactions 

• Many types 

  • Acute Hemolytic Transfusion Reaction 

    • Mostly caused by ABO incompatibility 

      • Given the wrong blood type  

    • Life-threatening 

    • Recipient’s antibodies attack and destroy donor RBCs 

  • Manifestations: 

    • Back/flank pain 

    • Fever/chills 

    • DIC 

    • Epitaxis(nose bleed) 

    • Shortness of breath 

    • Hypotension 

    • Tachycardia 

    • Hematuria 

    • Renal failure 

Acute Hemolytic Transfusion Reaction 

• Mostly caused by ABO incompatibility 

• Given the wrong blood type  

• Life-threatening 

• Recipient’s antibodies attack and destroy donor RBCs 

Manefestations of Acute Hemolytic Transfusion Reaction 

• Back/flank pain 

• Fever/chills 

• DIC 

• Epitaxis(nose bleed) 

• Shortness of breath 

• Hypotension 

• Tachycardia 

• Hematuria 

• Renal failure 

What is being described here?

• Abnormally high RBC mass with increased H&H(hematocrit and hemoglobin) 

• Causes: Dehydration, increased RBC proliferation (polycythemia vera), increase in erythropoietin levels- as a result of chronic tissue hypoxia secondary to smoking, high altitudes, chronic heart/lung diseases 

• Manifestations:  

  • Poor concentration 

  • Dizziness 

  • Headache 

  • Hearing/vision changes 

  • Hypertension 

  • Increased risk for blood clots 

 

polycythemia 

Causes of polycythemia :

• Dehydration

• increased RBC proliferation (polycythemia vera),

• increase in erythropoietin levels- as a result of chronic tissue hypoxia secondary to smoking

• high altitudes

• chronic heart/lung diseases 

Polycythemia manefestations:

• Poor concentration 

• Dizziness 

• Headache 

• Hearing/vision changes 

• Hypertension 

• Increased risk for blood clots 

Changes in RBCs Across the Lifespan 

• Neonate 

  • RBCs have shorter lifespan 

  • Increased bilirubin levels are related to increased RBC destruction and inability of the immature liver to conjugate bilirubin 

    • Remember when RBC are destroyed —> we get bilirubin 

  • Increased bilirubin levels are treated with phototherapy- UV light is absorbed by bilirubin in the skin and converted to soluble form of bilirubin that can be excreted 

  • Kernicterus: Rare neurologic syndrome caused by excessive accumulation of unconjugated bilirubin in infant brain cells 

  • Physiologic anemia at 2 months of age 

• Aging 

  • Decreased hemoglobin levels 

 

What is Kernicterus?

Rare neurologic syndrome caused by excessive accumulation of unconjugated bilirubin in infant brain cells