B7: CM H/O Exam 1

Hematology/oncology: where the cells are malignant, the prognosis is guarded, and the jokes are still inappropriate.

Anemia

most common disorder of the blood

1. blood loss

2. destruction of RBC

3. decreased RBC production

the three main causes of anemia

Lasthenie de Ferjol Syndrome

a very rare psychiatric pathology characterized by severe relapsing anaemia due to repeated self-induced hemorrhages

• GI or GU tract; obvious or occult

• Menstrual

• Retroperitoneal

• Nose bleeds, cutting, hematuria

main causes of blood loss that can lead to anemia

• Lack of iron, B12, folate

• Dysfunctional Bone marrow

• Suppressed bone marrow (radiation/chemo)

• Low levels erythropoietin, androgen, thyroid

causes of decreased RBC production that lead to anemia

Bone

where does erythropoiesis occur in adults?

Erythropoietin (EPO)

-enhances growth and differentiation of two erythroid progenitors to normoblasts of

increasing maturity.

Reticulocyte

Normoblast extrudes its nucleus to form a RBC and is identified as a ___________________

1%

Reticulocytes >_____% means bone marrow is working.

Hemolysis

The destruction of red blood cells which leads to the release of hemoglobin from within the red blood cells into the blood plasma

Bi-concave disk

shape of RBC

Normochromic Normocytic

Hypochromic

Hyperchromic

Hemoglobin S

variant of hemoglobin found in people with sickle cell

Hemoglobin C (and E)

variant of hemoglobin that causes mild chronic hemolytic anemia

Hemoglobin AS

variant of hemoglobin is heterozygous and causes sickle cell trait

Hemoglobin A (2 & 2)

Most common type of hemoglobin in adults

Oxygen

____________ binding changes structure of porphyrin heme ring

Bohr Effect

-States that in high acid ([H+]) conditions, side chains of Hb take on hydrogen; changes Hb conformation

-Result is LESS Hb oxygen content at given partial pressure of Oxygen

-O2 leaves Hb & goes to tissues

Right

__________ Shift:

-low affinity for O2

-O2 is released to the tissues

Right

__________ Shift:

-decreased pH

-increased CO2

-increased 2,3 BPG

-high temperature

Left

__________ Shift:

-increased pH

-decreased CO2

-decreased 2,3 BPG

Left

______________ Shift:

-high affinity for O2

Hemoglobin

Iron-containing oxygen-transport metalloprotein in RBC

Denatures the bond between oxygen and Hemoglobin

How does temp affect hemoglobin affinity for oxygen?

Right

__________ Shift:

acidosis

Left

__________ Shift:

alkalosis

Fetal Hemoglobin

Which has a greater affinity for oxygen?

Fetal or Adult Hemoglobin

Pagophagia

-desire to chew on ice

Pica

Eating non-nutritional items (Iron deficiency anemia)

Vitamin B12

__________________ is needed for normal functioning of the brain and nervous system, and the formation of red blood cells

Increasing

the body responds to low oxygen in the peripheral blood by ____________ cardiac output

Mean corpuscular volume (MCV)

-Represents the mean volume of individuals RBCs in blood sample

Microcytosis

defined as a MCV value less than 2 SD below the mean

( <80 fL in adults)

Normocytic

defined as MCV within 2 SD of the mean

Macrocytosis

defined as MCV value more than 2 SD above the mean

(>100 fL in adults)

Medications

Most common cause of macrocytic anemia in children

Mean corpuscular volume (MCV)

Factors that effect ____________ include iron deficiency, lead intoxication, anemia of chronic disease, & hemoglobinopathies (not sickle cell)

RDW (Red Cell Distribution width)

• A measure of the range in the volume and size of RBC

• A quantitative measure of variability of RBC sizes

• Values vary with age, usually ~ 12-14%

• Value increases in conditions in which there is large variation in RBC size.

• Helps differentiate different types of microcytic anemias

Normal

RDW in Thalassemia

>20

RDW in Iron deficiency

RDW (Red Cell Distribution width)

Conditions associated with increased _____________: Iron deficiency anemia, folate deficiency anemia, B-12 deficiency anemia, hemolytic anemia, sideroblastic anemia, transfusion, RBC Fragmentation, Hemoglobin H Disease & Alcohol abuse.

Anisocytosis

cells of different sizes

Poikilocytosis

cells of different shapes

Spherocytosis & reticulocytes

cells that are hyperchromic

1/3

Normocytic central pallor is ~ _________ the RBC diameter

Infection

if there is increased neutrophils on a peripheral smear, there is a concern for __________________

Leukemia or Lymphoma

if there are blasts on a peripheral smear, there is a concern for ________________________

Normal

Reticulocyte Count

Allows critical distinction between anemia arising from failure of RBC production versus that from increased RBC destruction

High

_____________ reticulocyte count with low hgb suggests the body is making RBCs

- anemia is due to blood loss or hemolysis

Low

_____________ reticulocyte count with low hgb suggests inadequate RBC production anemia is due to marrow failure (i.e. aplastic anemia)

0.5 - 2.0 %

normal reticulocyte count for adults

~100-120 days

how long do RBCs survive?

Methylene blue

reticulocytes can be counted manually when stained with _________________

Retic Index

corrected percentage for reticulocyte count

reticulocyte count x (hct/normal hct)

Inadequate

RPI < 3% with anemia = _______________ response of marrow

Appropriate

RPI > 3% with anemia = ______________ marrow response

<3%

RPI ___________% with anemia:

decreased production of reticulocytes (Myelodysplastic) & therefore RBCs.

>3%

RPI ___________% with anemia:

indicates loss of RBCs (from causes such as destruction, bleeding, etc.), with an increased

compensatory production of reticulocytes to replace lost RBCs.

Colon Cancer

when considering a diagnosis of Iron deficiency Anemia, you must rule out ____________________

Iron deficiency Anemia

-Hypochromic and microcytic cells

-most of the red cells are much smaller than the lymphocytes

-increased

platelet count

Duodenum and Upper Jejunum

Iron absorption occurs predominantly where?

pH

the absorption of iron is highly dependent on the __________ of the duodenum and upper jejunum

Iron deficiency Anemia

• Low iron,

• high TIBC (Total Iron Binding Capacity)

• Ferritin Low (High in anemia of chronic disease)

Iron deficiency Anemia

Ferritin

acute phase reactant protein that helps store iron in your body

-low level indicates a low level of stored iron

Transferrin Saturation

the ratio of serum iron and total iron-binding capacity

-his value tells a clinician how much serum iron are actually bound.

Total iron-binding capacity (TIBC)

medical laboratory test that measures the blood's capacity to bind iron with transferrin (may be HIGH if iron level is LOW).

Oral iron

Which treatment for iron deficiency anemia:

• Time consuming

• GI side effects are common

-150-200mg a day (3 pills a day)

IV Iron

Which treatment of Iron Deficiency Anemia

• Many formulations and dosing schemes

• Watch for reactions

• Much faster - can replete a years worth of iron in a dose or two

Anemia of Inflammation/ Anemia of Chronic Disease

acquired condition that is commonly observed in the clinical settings of:

• Infection

• Arthritis

• Malignancy

• trauma

• organ failure.

Anemia of Inflammation/ Anemia of Chronic Disease

What disorder:

-Initially anemia is mild, characterized primarily by a decrease in the number of RBCs

• Over time, the anemia becomes more severe, with hypochromic, microcytic erythrocytes

-results from a host-defense mechanism designed to sequester iron from the invading pathogens

Anemia of Inflammation/ Anemia of Chronic Disease

Pathogenesis:

• First, there is a modest (<10%) shortening of red cell survival which creates a demand for a slight increase in bone marrow red cell production.

-The bone marrow cannot respond adequately owing to impaired erythropoiesis and impaired mobilization of iron from the reticuloendothelial cells

Hepcidin

an endogenous antimicrobial peptide secreted by the liver, has been identified as controlling the level of plasma iron by regulating the intestinal absorption of dietary iron as well as the release of macrophages and the transfer or iron stored in the hepatocytes

Hepcidin

Increase in _____________level in the course of inflammatory disease may be a significant mediator of the accompanying anemia

Lead Toxicity

-Basophilic Stippling

-hct and hb moderately low

-normochromic and normocytic or hypochromic and microcytic

-Eosinophilia

Sideroblastic Anemia

What disorder:

-rare blood disorder characterized by the bone marrow's inability to manufacture normal red blood cells

-normocytic-normochromic anemia with high RDW

-microcytic-hypochromic anemia, particularly with increased serum iron, ferritin, and transferrin saturation

Hereditary Sideroblastic Anemia

-X-linked Recessive

-more commonly in young males, maternal uncles and cousins.

-generally manifests during the first three decades of life especially during adolescence

-inability of bone marrow to make normal RBCs

Acquired Sideroblastic Anemia

anemia due to prolonged exposure to toxins like alcohol, lead, drugs or nutritional imbalances such as deficiency in folic acid, deficiency in copper or excess zinc

-usually seen in patients over 65 year of age but it can be present as early as mid to late fifties

Myelodysplastic Syndrome (MDS)

Idiopathic Sideroblastic Anemia is aka:

Myelodysplastic Syndrome (MDS)

bone marrow dysfunction disorder which can develop into aplastic anemia requiring bone marrow or stem cell transplantation

Sideroblastic Anemia

• Serum iron increased

• transferrin iron saturation percentage increased

• ferritin increased

• transferrin is decreased.

• TIBC is normal to decreased; serum transferrin receptor is normal to high

-MCV normal to slightly increased

-RDW increased

-White blood cells and platelets are decreased.

Blood Transfusions

Treatment for Sideroblastic anemia if the cause of the pts anemia cannot be determined

Pyridoxine (b6)

In rare instances of sideroblastic anemia, treatment with oral ________________________ benefits patients whose who have had the condition since birth

anemia

a serious sign of disease, NEVER NORMAL

Romberg sign

loss of balance standing with eyes closed

angular cheilitis (cracking at corners of mouth), glossitis, jaundice

oral/skin findings of macrocytic anemia

CBCwd, peripheral smear, reticulocyte count

basic initial labs for anemia

b12 level, folate level, MMA and homocysteine

focused initial labs for anemia

WBC, RBC, H&H, MCV

most important aspects of CBC to look at in anemia workup

MCV

Represents the mean volume of individuals RBCs in blood sample

macrocytosis

MCV value more than 2 SD above the mean (>100 fL in adults)

-RBC larger than normal at all stages

-classified as megaloblastic or non-megaloblastic

normocytic

MCV within 2 SD of the mean

microcytosis

MCV value less than 2 SD below the mean( <80 fL in adults)

medications

most common cause of macrocytic anemia in children

megaloblastic anemia

caused by impaired DNA synthesis

-Deficient Thymidylate leads to arrest in cell maturation

-Marked increase in MCV is common (MCV >110)

b12 deficiency

folate deficiency

medication associated

hereditary orotic aciduria

causes of megaloblastic anemia

Reticulocytosis

Hypothyroidism

Liver disease

Postsplenectomy anemia

Myelodysplastic syndromes

Aplastic anemia

Dyserthropoetic anemia

Down syndrome

causes of non-megaloblastic anemia