Anemia and RBC disorders

What are the three main components of a CBC?

1. RBC count

2. WBC count

3. Platelet count

What are three factors that can affect the CBC?

1. age

2. sex

3. race

What is the red iron- based protein in RBCs? What does it transport ?

hemoglobin ; binds and transports CO2 and O2

describe the heme and globin content in hemoglobin

there are 4 molecules of heme each has one iron ion

there are 4 molecules of globulin, 2 alpha and 2 beta chains

What is the shape of a RBC? what is the purpose of this shape?

biconcave disc; provides increased SA for O2 and CO2 also enables them to bend and flex when entering small capillaris

Mature RBCs lack a ________ and most cellular organelles, they usually survive about ____ days.

nucleus ; 120

What is RBC count?

total number of RBC per unit of whole blood

What physiological variants effect the RBC count?

exercise, age, altitude, pregnancy, drugs

What can increase/ decrease RBC count?

increase: secondary polycythemia, dehydration (hemoconcentration), polycythemia vera

decrease: anemia, chronic/ acute blood loss, fluid overload, bone marrow suppression/disease

What is hematocrit (HCT)? how is it calculated?

the volume percentage of RBCs in whole blood, calculated by multiplying RBC count by mean corpuscular volume

What are physiological variants that affect HCT?

age pregnancy and drugs

How is hematocrit increases/decreased?

increased: any condition that increases RBCs (polycythemia, dehydration, physical exercise)

decreased: any conditions that decrease RBCs (anemia, acute hemorrhage, bone marrow suppression/ disease)

What is Hgb or Hb?

the amount of hemoglobin in a given volume of whole blood

what are the physiological factors that can affect Hgb?

age, high altitude, excessive fluid intake, pregnancy, drugs

what can increase/ decrease hemoglobin?

increased: hemoconcentration (dehydration, severe burns, vomiting), polycythemia, extreme physical exercise, hyperlipidemia

decrease: anemia, acute hemorrhage, hemodilution, bone marrow disease

A hematocrit

heart failure and death; spontaneous clotting leading to thrombosis

a hemoglobin value of < 5.0 g/dL leads to ___________________, hemoglobin value >20.0 g/dL results in _________________________.

heart failure and death, hemoconcentration and clogging of capillaries

What is MCV?

average volume of RBC

how is MCV increased/decreased?

increased: liver disease, alcohol abuse, HIV/AIDs, hemochromatosis ect.

decreased: iron definency, thalassemia, lead poisoning ect.

anemia can increase or decrease MCV count it depends on the type of anemia

What is MCH?

average amount of hemoglobin per RBC in absolute units

How is MCH calculated?

(hbg / RBC count ) x 10

how is MCH increased/ decreased?

increased: macrocytosis, hemochromatosis

decreased: microcytosis, hypochromia, lead poisoning most anemias

MCV can indicate if RBCs have ________ but it CANNOT indicate _________.

normal mean value; normal shape

What is MCHC- mean corpuscular hemoglobin concentration?

average hemoglobin concentration in RBC

how is MCHC calculated?

(Hgb/ HCT) x 100

how is MCHC increased/ decreased?

increased : marked spherocytosis (abnormally round RBCc), immune hemolysis

decreased: hypochromic anemia, anemia of chronic disease

When the MCV is low RBCs are called __________, when MCV is high RBCs are called ___________.

microcytic; macrocytic

When the RBC have a high Hg they are called _____________, when RBC have a low Hg they are called _______________.

hyperchromic; hypochromic

What is red cell distribution width - RDW?

measure of variation of RBC volume

How is RDW calculated?

(standard deviation of MCV/ mean MCV) x 100

abnormally high RDW is called ?

anisocytosis

RDW may in increased by?

certain types of anemias like sickle cell

leukemia

What are reticulocytes?

immature RBCs that contain cytoplasmic RNA

What is the reticulocyte count a indication of?

how rapidly reticulocytes are produced by the bone marrow and released into the blood stream and reflects the erythropoietic activity of the bone marrow

how is reticulocyte count usually expressed?

percent of the number of reticulocytes per total number of RBCs counted

What is the normal number of reticulocytes in adults?

25,000- 85,000 per whole blood

What is the difference between reticulocytosis and reticulopenia?

reticulocytosis: increase reiculocytes count

reticulopenia: decreased reticulocyte count

Anemia is defined as?

decrease in RBC or hemoglobin content

polycythemia is defined as?

increase of RBC

what the difference between primary and secondary polycythemia?

primary: bone marrow produces to many RBC on its own

secondary: the body produces to much erythropoietin and stimulates the bone marrow to make more RBCs

What usually causes secondary polycythemia?

chronic lung disease

high altitude living

obstructive sleep apnea

cyanotic heart disease

What are the three basic mechanisms that can cause anemia?

1. reduced/ ineffective erythropoiesis

2. increased RBC loss or reduced RBC life span

3. dilutional anemia

symptoms of anemia vary vastly depending on?

hematocrit level; when the HCT is greater than 30% anemia is asymptomatic when it less than 30% symptoms are usually, weakness, vertigo, headaches , tinnitus, spots before eyes, fatigue, drowsiness, irritability and bizarre behavior

What is the difference between anemias characterized by:

microcytic- hyporchromic RBC

normochromic- normocytic RBC

macrocytic (megaloblastic) RBC

microcytic- hyporchromic RBC = RBC are small and pale and there is a defect in hemo or globin synthesis

normochromic- normocytic RBC = RBC are normal in size and Hg levels are normal but there is not enough RBCs being produced

macrocytic (megaloblastic) RBC = RBC are larger and there is a defect in DNA synthesis

what is iron deficiency anemia (IDA)?

anemia due to decreased iron

What is the most common cause of anemia in the US?

iron deficiency anemia

IDA is most common in what populations?

1. infants and toddlers

2. pregnant patients

3. females age 12 -49 from menstrual loss

What are four causes of IDA?

1. blood loss due to:

- GI bleeding frequently associated with ulcers/ asprin

- menstral bleeding

- certain cancers like esophagus, stomach or GI cancer

2. poor iron intake

3. poor iron absortion

4. increased demand for iron

What is the difference in onset with chronic and acute blood loss pertaining to IDA?

chronic: poor diet slow blood loss

acute: rapid blood loss

What is the clinical presentation of IDA?

(remember that usually mild anemia with HCT over 30% is asymptomatic but severe anemia with HCT under 30% will show signs and symptoms)

- skin, mucosal, and conjuctical pallor

- irraitability, decreased concentration

- weakness

- SOB

- brittle fingernails and koilonychia (spooning of nails)

- headache

- decreased appetite

- Pica (unusal craving for non-nutrional substances)

- dysphagia

- tachycardia

what is the triad of IDA, dysphagia and upper esophageal webs called?

Plummer- Vinson syndrome

What are the oral manifestations of IDA ?

- angular chelitis

- atrophic glossitis (smooth, shiny, red inflamed tongue)

- generalized mucosal atrophy (thin, smooth, red mucosa)

- diffuse or patchy atrophy of dorsal tongue papillae

- glossodynia (tenderness/ burning of the tongue)

Iron deficiency develops in stages, what are they are how are the laboratory test affect in each stage?

1. store irons runs out: body uses up iron stored in bone marrow and lab test show serum ferritin decreased (because it reflects stored iron), there is not a sustainable amount of iron left in bone marrow

2. iron in the blood decreases: the body's iron store are depleted, lab tests show transferrin increased which is a protein that transport iron in the blood, body makes more to try and capture more iron. Total iron-binding capacity TIBC is also increased because more transferrin is present

3. anemia develops: w/o enough iron bone marrow cant produce hemoglobin and will result in smaller and fewer RBCs = microhypochromic anemia

What does the peripheral blood smear show in IDA?

microcytic hypochromic RBCs with wide area of central pallor, anisocytosis (variation to size), poikilocytosis (abnormal variation in shape)

The CBC in IDA shows low levels in ________ and high levels in _____

low: RBC count, Hgb, HCT, MCV, MCH,MCHC

high RDW

(platelet are often elvated)

How do you treat IDA?

iron supplementation usually in the form of ferrous sulfate

When treating a patient with IDA when should repletion of reticulocytes occur?

7-14 days

What is anemia of chronic disease (ACD)?

Also called anemia of chronic inflammation. It is the second most common anemia in the US, especially in older and hospitalized adults. Caused by long-term inflammation from cancer, infections, or autoimmune diseases.

What are the some of the important underlying diseases of ACD?

neoplasms like hodgkins, carcinomas of lung and breast

microbial infection, osteomyelitis, bacterial endocarditis, lung abscess

autoimmune disease like RA, sarcoidosis, systemic lupusm erythematosus, inflammatory bowel disease

how do inflammatory cytokines like IL-6 cause ACD?

IL-6 increase hepcidin production in the liver, which blocks ferroportin, traps iron in macrophages, reduces iron absorption, and decreases EPO. This reduces RBC production in the bone marrow.

What are the symptoms and blood findings of ACD?

Fatigue, weakness, pallor, shortness of breath, and headaches. Usually mild to moderate normocytic, normochromic anemia with low reticulocytes. Some cases are microcytic and hypochromic.

How is anemia of chronic disease treated?

Treat the underlying disease causing inflammation to improve symptoms and restore hemoglobin levels.

What is pernicious anemia?

A megaloblastic, macrocytic anemia caused by vitamin B12 deficiency

What is pernicious anemia characterized by?

atrophic gastritis (thinning of stomach lining) and achlorhydria (lack of stomach acid)

What conditions and genetic factors are associated with pernicious anemia?

Associated with autoimmune diseases (type 1 diabetes, Graves disease, Addison disease) and possible H. pylori infection. Rare hereditary forms occur more often in people of Northern European ancestry, especially Scandinavian.

Who is most commonly affected by pernicious anemia?

Mostly older adults (40-70 years), slightly more common in women, especially Black women a rare form is more frequent in patients of northern European and Scandinavian descent

What causes pernicious anemia?

Autoimmune destruction of the stomach lining damages parietal cells, decreasing intrinsic factor needed for vitamin B12 absorption in the terminal ileum. Over 70% have parietal cell antibodies and over 50% have intrinsic factor antibodies.

What are the histological changes in the stomach with pernicious anemia?

Atrophy of gastric glands, loss of parietal cells, achlorhydria (lack of stomach acid), and intestinal metaplasia with goblet cells.

What are the clinical symptoms of pernicious anemia?

Symptoms develop slowly and may initially be absent. The classic triad is generalized weakness, glossitis, and paresthesias. Other symptoms include loss of appetite, heartburn, nausea, vomiting, and mild jaundice causing lemon-yellow skin.

What neurological problems occur with pernicious anemia?

Vitamin B12 deficiency impairs methionine synthase and methionine production, causing nerve problems. Initially, patients experience tingling (paresthesia) and decreased vibration and position sense, followed by difficulty walking and balancing. Severe cases may cause memory loss, delirium, or dementia.

What are the oral manifestations of pernicious anemia?

Glossitis causing a sore or burning tongue, sometimes affecting the lips and cheeks. The oral mucosa may show patchy or widespread redness (erythema) and thinning (atrophy).

Can vitamin B12 deficiency cause symptoms before anemia develops?

Yes. Neurological and other symptoms may appear months before anemia or RBC changes. Anemia is absent in 20% of patients, and macrocytosis is absent in over 30%.

What are the laboratory findings in vitamin B12 deficiency?

Low serum B12 (often below 100 pg/mL), increased MCV (110-140 fL), increased MCH, normal MCHC, and decreased reticulocytes. Severe cases may have low platelets and WBCs.

What are the peripheral blood smear findings in vitamin B12 deficiency?

Anisocytosis (different RBC sizes), poikilocytosis (different RBC shapes), large oval RBCs (macro-ovalocytes), and hypersegmented neutrophils (more than 5 lobes).

How can vitamin B12 deficiency be distinguished from folate deficiency?

Both can increase homocysteine, but only vitamin B12 deficiency typically increases methylmalonic acid.

How is pernicious anemia treated?

Vitamin B12 replacement, often through intramuscular injections. Early treatment is important because neurological damage may become permanent.

Why should nitrous oxide sedation be avoided in patients with uncontrolled pernicious anemia?

Nitrous oxide inactivates vitamin B12 and its dependent enzyme methionine synthase, potentially worsening neurological damage.

What causes folate (folic acid) deficiency anemia?

Usually caused by poor dietary intake of green vegetables and fruits, increased metabolic needs, or problems with absorption in the jejunum or folate metabolism.

How does folate deficiency lead to anemia?

The body has limited folate stores, so deficiency develops within months. Low folate prevents normal DNA replication, causing megaloblastic, macrocytic anemia.

What are the clinical symptoms of folate deficiency anemia?

Slow onset of weakness and fatigue. Symptoms are similar to vitamin B12 deficiency, but folate deficiency does not cause neurological problems.

What are the laboratory findings of folate deficiency anemia, and how is it different from vitamin B12 deficiency?

Megaloblastic, macrocytic anemia with low serum and RBC folate, increased homocysteine, and normal methylmalonic acid. Unlike B12 deficiency, methylmalonic acid does not increase.

What is hemolytic anemia?

Anemia caused by increased RBC destruction or a shortened RBC lifespan. It can be acute or chronic.

What is the difference between congenital and acquired hemolytic anemia?

Congenital: Caused by an inherited defect in RBCs, usually appears in childhood, and often has a family history.

Acquired: Caused by bone marrow or systemic diseases that destroy otherwise normal RBCs. Family history is usually normal, and the onset can often be identified.

What causes congenital hemolytic anemia?

Inherited defects in hemoglobin structure, RBC metabolism, or hemoglobin production, causing RBC destruction.

What are the complications of congenital hemolytic anemia?

Jaundice, bilirubin gallstones, iron overload (hemosiderosis), fatigue, weakness, and heart enlargement or failure.

What are hemoglobinopathies?

Inherited abnormalities in hemoglobin that cause hemolytic anemia. Abnormal globin chains can be detected by hemoglobin electrophoresis.

What are the three types of normal hemoglobin in adults?

HbA (95-98%) is the main adult hemoglobin with 2 alpha and 2 beta chains. HbA2 (2-3%) and HbF (0.8-2%) are present in small amounts.

What is the difference between a hemoglobin trait and disease?

Trait: Heterozygous (one abnormal gene), usually no symptoms.

Disease: Homozygous (two abnormal genes) or two different abnormal hemoglobin genes, usually causing hemolysis.

What is sickle cell anemia, and what causes it?

The most common inherited hemolytic anemia, caused by a mutation in the beta-globin chain (valine replaces glutamic acid), producing abnormal hemoglobin S (HbS).

What is the most common hereditary hemolytic anemia?

sickle cell

How does HbS cause sickling and hemolysis

Low oxygen (hypoxia) or acidosis causes HbS to form long strands, making RBCs sickle-shaped. These cells block small blood vessels and are destroyed early, mainly in the spleen. RBC lifespan decreases to about 25 days.

What is the difference between sickle cell disease and sickle cell trait?

Sickle cell disease: Homozygous HbS, with 85-95% HbS, causing severe hemolytic anemia and complications.

Sickle cell trait: Heterozygous HbS, with 30-45% HbS, usually asymptomatic with a normal life expectancy. The trait provides some protection against severe malaria.

hat are vaso-occlusive crises, and what triggers them?

Painful episodes caused by sickled RBCs blocking small blood vessels, leading to tissue ischemia. Common triggers include hypoxia, dehydration, infection, fever, acidosis, stress, and temperature changes.

What are the major complications of sickle cell disease?

- Splenic sequestration: Enlarged spleen in children, followed by repeated damage and autosplenectomy (loss of spleen function).

- Dactylitis: Painful swelling of hands and feet, often the first symptom in children.

- Stroke: Caused by blood vessel damage and blockage.

- Acute chest syndrome: Fever, chest pain, cough, and breathing problems; leading cause of death in adults.

Infections: Especially Streptococcus pneumoniae; major cause of death in children.

- Renal failure: Progressive kidney damage.

- Bone damage: Avascular necrosis and osteomyelitis, often involving Salmonella or S. aureus.

What are the oral manifestations of sickle cell disease?

Oral pallor and jaundice, delayed tooth eruption, enamel hypoplasia, and mandibular ischemic necrosis. Radiographs may show widened marrow spaces, fewer trabeculae, a step-ladder pattern, and areas of dense bone.

What are the laboratory findings of sickle cell disease?

Moderate to severe anemia (Hb 6-10 g/dL), increased reticulocytes (10-25%), elevated LDH, and variable WBC counts. Blood smears show sickled RBCs, target cells, and nucleated RBCs.

What is thalassemia, and what are its two types?

An inherited disorder causing decreased production of hemoglobin chains.

Alpha-thalassemia: Decreased alpha-globin production.

Beta-thalassemia: Decreased beta-globin production.

What causes beta-thalassemia, and how does it lead to anemia?

Inherited mutations reduce beta-globin production, causing small, pale RBCs (microcytic, hypochromic). Excess alpha chains accumulate and damage RBCs and their precursors, causing hemolysis and decreased RBC production. It is especially common in Mediterranean populations.

What are the three classifications of beta-thalassemia?

Minor: Heterozygous, mild or asymptomatic anemia with microcytosis and normal lifespan.

Intermedia: Moderate anemia, usually without regular transfusion dependence.

Major (Cooley anemia): Homozygous or severe genetic forms, causing severe anemia and regular transfusion dependence.

What are the clinical complications of beta-thalassemia major?

Severe anemia beginning around 6 months of age, delayed growth and puberty, skeletal deformities, enlarged liver and spleen, jaundice, gallstones, and possible cirrhosis. Blood transfusions can cause iron overload, leading to heart failure, arrhythmias, and endocrine problems.