Hematology: RBCs

the production of all blood cells in the bone marrow

hematopoiesis

What is the purpose of RBCs?

carry oxygen to the tissues in exchange of CO2 then circulate back to the lungs for oxygen

What is the lifecycle of a normal RBC?

120 days

the production of RBCs in the bone marrow

erythropoiesis

What are the functions of the following?

kidneys

liver

bone marrow

spleen

kidneys: secrete erythropoietin for RBC production

liver: stores RBCs

bone marrow: site of RBC production

spleen: recycles and destroys RBCs

glycoprotein secreted in kidneys in response to the need for more RBCs

erythropoietin

What 2 things stimulate erythropoietin (which signals for RBC production?

1. low oxygen to tissues (hypoxia)

2. low intracellular oxygen tension (PO2)

What 4 conditions stimulate erythropoiesis?

1. anemia

2. cardiac or pulmonary disorders

3. abnormal hemoglobins

4. high altitudes

Why do levels of erythropoietin *decrease* in cases of renal insufficiency or end stage renal disease?

because kidneys cannot secrete enough erythropoietin

List the maturation process of the RBC starting with pronormoblast (tricky names). (6)

1. pronormoblast

2. basophilic normoblast

3. polychromatophilic normoblast

4. orthochromatophilic normoblast

5. polychromatophilic erythrocyte

6. erythrocyte

List the maturation process of the RBC starting with rubriblast (easy names). (6)

1. rubriblast

2. prorubricyte

3. rubricyte

4. metarubricyte

5. reticulocyte

6. erythrocyte

Where are normoblasts commonly seen?

bone marrow (blasts should not been seen in the peripheral blood in a healthy individual)

Where are reticulocytes commonly seen?

peripheral smear

protein that serves as a vehicle for the transport of oxygen and carbon dioxide

hemoglobin

What part of the RBC is iron incorporated into the porphyrin ring?

red cell mitochondira

Heme and globin chains are combined in what part of the RBC?

cytoplasm

What is the combination of heme and globin when are they combined in the cytoplasm?

hemoglobin

List the alpha-like and non-alpha chains.

alpha-like: alpha, zeta

non-alpha: beta, delta, epsilon, gamma

What are the 4 types of fetal hemoglobin?

Gower I, Gower II, Portland's, Hgb F

What is the chain combination for Gower I?

Gower I= 2 *zeta*, 2 *epsilon*

What is the chain combination for Portland's?

Portland's= 2 *zeta*, 2 *gamma*

What is the chain combination for Gower II?

Gower II= 2 alpha, 2 *epsilon*

What is the chain combination for HgF?

Hgb F= 2 alpha, 2 *gamma*

What are the 4 types of adult hemoglobin?

Hgb A, Hgb A1c, Hgb A2, Hgb F

What is the chain combination for Hgb A?

Hgb A= 2 alpha, 2 *beta*

What is the chain combination for Hgb A1c?

Hgb A1c= 2 alpha, 2 *beta-NH-glucose*

(diabetics, glucose, A1c checks)

What is the chain combination for Hgb A2?

Hgb A2= 2 alpha, 2 *delta*

What are the Y and X axis on an oxygen dissociation curve?

Y= functional saturation of hemoglobin

X= concentration of oxygen measured as PO2

What 5 components cause a shift in the oxygen dissociation curve?

1. temperature

2. CO2

3. O2

4. 2,3-BPG concentration

5. pH

What is the normal line on the oxygen dissociation curve?

pH 7.4

PO2 26mmHg

hemoglobin 50% saturated with oxygen

a product of the glycolytic pathway that decreases the oxygen affinity of hemoglobin

2,3-BPG

What happens when 2,3-BPG increases?

oxygen is released into tissues, shift right

What are the two implications of a left shift in the oxygen dissociation curve?

1. increased oxygen affinity (R state)

2. reduced oxygen delivery to tissues

What are the two implications of a right shift in the oxygen dissociation curve?

1. reduced oxygen affinity (T state)

2. increased oxygen delivery to tissues

Shift left or right?

- high pH

- low temp

- low 2,3-BPG

- fetal Hgb

- methemoglobinemia

- carboxyhemoglobinemia

- high O2 affinity hgb variants

left shift

Shift left or right?

- low pH

- increased CO2

- high temp

- high 2,3-BPG

- low O2 affinity hgb variants

right shift

What are the normal hemoglobin reference ranges for:

males

females

newborns

males: 13-17 g/dL

females: 12-16 g/dL

newborns: 14-22 g/dL

Deoxyhemoglobin contains iron in a (reduced/oxidized) state, represented as Fe (++/+++)

*Deoxyhemoglobin* contains iron in an *oxidized* state, represented as Fe *+++* (ferric)

Oxyhemoglobin contains iron in a (reduced/oxidized) state, represented as Fe (++/+++)

*Oxyhemoglobin* contains iron in a *reduced* state, represented as Fe *++* (ferrous)

What are the 3 clinically significant hemoglobins?

carboxyhemoglobin, methemoglobin, sulfhemoglobin

What is carboxyhemoglobin made up of?

hemoglobin and carbon monoxide (CO)

What color is carboxyhemoglobin?

cherry red

What type of pateints have carboxyhemoglobin?

pts who smoke, live in high pollution areas, exposed to smoke (e.g. house fires)

What is the toxic level for carboxyhemoglobin?

5g/dL

What is another name for methemoglobin?

deoxyhemoglobin

What color is methemoglobin?

chocolate brown (oxidized blood)

Is methemoglobin reversible?

yes

Increased levels of methemoglobin are seen in pts who are exposed to what 3 things?

oxidizing chemicals, drugs, aniline dyes

Cyanosis occurs at ____% methemoglobin.

10%

Hypoxia occurs at ____% methemoglobin.

60%

What is sulfhemoglobin a combination of?

hemoglobin and sulfur

What color is sulfhemoglobin?

lavendar

Increased levels of sulfhemoglobin are seen in pts who are exposed to what 2 things?

sulfa drugs and trinitroluene

Is the sulfhemoglobin compound reversible?

no, the compound is very stable

Sulfhemoglobin is toxic at ____%

0.5%

the reagent used in cyanmethemoblobin method

Drabkins

What are the 3 components of Drabkins?

sodium bicarbonate, KCN (potassium cyanide), potassium ferricyanide

What is the absorbance peak of Cyanmethemoglobin?

540nm

Which clinically signficant hemoglobin is not tested by the Cyanmethgb method?

sulfhemoglobin

Using the specific gravity method to test hemoglobin concentrations, what do the following results mean?

drop floats to top

drop sinks to bottom

drop does not float or sink

drop floats to top: lower conc.

drop sinks to bottom: higher conc.

drop does not float or sink: same conc.

What is the solution used to test the hemoglobin concentration of the specific gravity test?

copper sulfate

What 3 problems interfere with hemoglobinometry? How do you solve them?

1. High WBC count-- add blood to reagent, centrifuge and WBC will sink to bottom

2. Lipemic-- saline replacement

3. variant inherited hemoglobinopathies (Hgb S or C disease)-- dilute 1:1 with water to lyse RBCs, add reagent and multiply results by 2

What is the rule of 3 in regards to H/H?

hemoglobin should match hematocrit.

hemoglobin x3 = hematocrit +/-3

% RBCs in blood

hematocrit

What are the hematocrit ranges for the following:

males

females

newborns

males: 40-54%

females: 36-47%

newborns: 50-62%

What is the most reproducible test in the lab?

hematocrit

List two problems that can cause falsely low hematocrits when using the manual method.

1. incomplete sealing (no clay=RBCs spill out)

2. over-anticoagulation of specimen

List two problems that can cause falsely elevated hematocrits.

1. allowing hematocrit tubes to sit too long in the centrifuge

2. trapped plasma with the packed red cell layer

Why do newborns have such a high number of RBCs?

because they are growing and have a high heart rate

nucleated RBCs, seen in people with a high rate of erythropoiesis

orthochromatic normoblast/metarubricyte

the glycolytic pathway that produces 2,3-BPG

Embden-Meyerhoff pathway