Intro to Heme (CMPP)

Hematology

The study of blood and blood disorders

What are the functions of blood?

Transport (O2 + Nutrients + Metabolic Waste)

Regulation of Temp

Immune System Support

Hemostasis + Circulating Coagulation Factors

Signal Transmission (Hormones)

How much blood is present in the body?

9 pints = Females

12 pints = Males

How much blood is given during a donation

1 pint

How long should a person wait between blood donation

8 weeks

What are the main components of blood?

Plasma (55%)

Cells (45%)

What makes up the plasma of blood?

Water (90%)

Molecules (10%) like protein, fat, salt, hormones, Ab, and coagulation factor

What cells are present in blood?

RBC

WBC

Platlets

Centrifugation

A process where a fluid is spun to separate its components by their density

How does blood layer (top to bottom) after centrifugtion

Plasma

Buffy Coat (WBC and PTL)

RBCs

What must be done to blood before centrifugation

Anticoagulation

When does hematopoiesis begin?

First weeks of gestation

In utero, where does hematopoiesis begin

Yolk Sac

How does the location of hematopoiesis travel with development?

1. Yolk Sac

2. Liver and Spleen

3. Bone Marrow

Red Marrow

The major site of healthy hematopoiesis found in bones

What type of bones do most of the hematopoiesis

Flat Bones

Ends of Long Bones

Yellow Marrow

A type of bone marrow found in the shaft of bones that store fat

When will the adult body do hematopoiesis outside of the red marrow?

Pathologic State

What is the main regulator of hematopoiesis

EPO

Erythropoietin (EPO)

A hormone in the kidney produced during hypoxia to promote HSCs to become RBCs

What are the regulators of hematopoiesis

EPO (#1)

Thyroid Hormones

Androgens

Hematopoietic Stem Cells (HSCs)

A precursor cell in bone marrow that can differentiate into all of the cell types in blood

Granulocyte Mast Colony Stimulation Factor (GM-CSF)

A hormone that promotes HSCs into WBCs

Thrombopoietin (TPO)

A hormone that promotes HSCs into PTL

How long does it take a HSC to become a RBC

7-10 days

How does a HSC change into a RBC

Shrinks

Biconcave

Lose nucleus

Become red due to increased heme production

At what stage of development will a non-mature RBC leave the bone marrow

Reticulocyte

Reticulocyte

An anucleate precursor to RBC that can be found in circulation

How long in circulation does a reticulocyte take to mature into a RBC

1-2 days

What is the normal value for reticulocyte count

< 2.5 %

What is the best blood test for measuring bone marrow function

Reticulocyte Count

What is the most abundant cell in blood

RBC

What is the main function of RBC

Gas Exchange

What is the benefit of a biconcave cell

Increases SA

Flexibility

What is the lifespan of a RBC

120 days

What is the normal levels for Hgb

Male = 13.5 - 17.5 g/dL

Female = 12 - 16 g/dL

What makes up Hgb

heme

globin

What makes up a heme

Porphyrin Ring

Ferrous Iron (2+)

What are the usual heme groups

Alpha 1

Alpha 2

Beta 1

Beta 2

Methemoglobinemia

A conditon where heme is produce with ferric iron rather than ferrous

What can cause methmoglobinemia

Genetic

Dapsone

Antimalarials

Topical Anesthetics

Pulse Oximetry

An estimate of the saturation of blood

Arterial Blood Gas (ABGs)

A blood test that can precisly determine the oxygen in blood

What can cause a false normal / high pulse ox reading

CO

Elevated A1C

Skin Pigment

What can cause a false low pulse ox

Nail Polish

Poor Perfusion

Hemoglobinopathy (Sickle Cell / Methemoglobinemia / G6PD deficiency)

What is the most common type of Hgb

Hgb A

Reticuloendothelial System

A process where macrophages in the spleen and bone marrow eat old RBC

Extravascular Hemolysis

The breaking down of Hgb outside of circulation, usually in the spleen and bone marrow

What will globin break down to

Amino Acids

What will heme break down into

Porphyrin

Iron

How does porphyrin breakdown

1. Porphyrin → Biliverdin (Green)

2. Biliverdin → Unconjugated Bilirubin

3. Bilirubin is transported by albumin to the liver

4. Unconjugated bilirubin → Conjugated Bilirubin

Intravascular Hemolysis

A process where a small amount of RBC will break down in circulation

What can we use as a marker for intravascular hemolysis

LDH

Lactate Dehydrogenase (LDH)

An enzyme found in all cells in the body

Commonly used as a marker for tissue breakdown

Pseudohyperkalemia

A state of high K due to the breakdown of RBC inside circulation

What are the sources of iron in the body

Dietary

Recycled

What end of iron balance does the body struggle

Excertion

Transferrin

A glycoprotein made by the liver that transports iron ion through the blood

Ferritin

A storage protein that stores thousands of iron ion

Hemosiderin

A storage protein that stores thousands of ferritin molecules

How does iron change across sex

Men have higher iron storage than pre-menopausal women due to menses, pregnancy, and lactation

What is the difference between intaking heme based iron and non-heme based iron

Heme iron is more bioavailable than non-heme irion

How does iron get absorbed

1. Iron is taken in as ferric iron

2. HCl in the stomach break down ferric iron into ferrous iron

3. Duodenal Enterocytes will absorb ferrous iron

4. Ferrous iron is converted back into ferric iron to bind with transferrin

What supplement can help iron absorption

Vitamin C

What supplement can inhibit iron absorption

Ca

Once absorbed, where will iron go in the body

Bone Marrow = RBC production

Liver = Storage

HFE Protein

A protein in the liver that detects when the body is in a state of high iron

Releases hepcidin

Hepcidin

A protein that will repress the expression of FPN to reduce iron absorption and reduce release from storage

Ferroprotein (FPN)

A protein that is responsible for iron intake

• Promotes absorption from duodenum

• Promotes release from macrophages

  • Promotes release from ferritin in the liver

How does the body regulate iron

• If high = Hepcidin is released and represses FPN, reducing absorption and release

• If low = Hepcidin is not released/ FPN promotes more absorption and release from storage

What are the levels of iron toxicity

< 20 mg/kg = Asymptomatic

20 - 60 = GI symptoms

60 - 120 = Systemic Toxicity (Acidosis and Hepatotoxic)
>120 = Can be lethal

What is included in a CBC w/o diff

• Hgb

• HCT

• WBC

• PTL

• RBC Indices

What are the RBC indices

• MCV

• MCH

• MCHC

• RDW

What is a differential in terms of a CBC

A percentage of WBCs that are of certain types (Neutrophils, Eosinophils, etc.)

What is the normal relationship between Hgb and HCT

HCT = Hgb * 3

What is the first lab value in assessing for anemia

Hgb

What are the panic values for Hgb

< 7 = MI / HF / Death

> 20 = Clogging and Hemoconcentration

Hematocrit (HCT)

A value of the % of blood that is RBCs

What is normal HCT values?

Male = 41-53%

Female = 36-46%

Mean Corpuscular Volume (MCV)

A value of the average size of any RBC

What are the values for MCV

> 80 = Microcytic

80 - 100 = Normocytic

> 100 = Macrocytic

Mean Corpuscular Hemoglobin (MCH)

A value of the average weight of Hgb per RBC

What is the forumla of MCH

Total Hgb Mass / # of RBC

MCH will trend with what other value?

MCV

Mean Corpuscular Hemoglobin Concentration (MCHC)

The average concentration of Hgb in a volume of RBC

What is the forumla of MCHC

Hgb / HCT

What are values of MCHC

< 32 = Hypochromic

32-36 = Normochromic

> 36 = Hyperchromic

What value shows cellular dehydration

MCHC > 36 (Hyperchromic)

Red Cell Distribution (RDW)

A histogram where the size of RBC is plotted by frequency

Ansiocytosis

Variation in size of RBC

What can cause low to normal RDW?

Thalassemia

Chronic Disease

What can cause high RDW

Nutrient Deficiency (Iron / B12 / Folate)

ETOH

What is the normal value for reticulocyte count

0.5% - 2.5%

Peripheral Blood Smear

A microscopic test that looks for RBC shape and size

Poikilocytosis

A variation in RBC shape

Spherocytosis

A condition where RBC appears spherical

What can cause spherocytosis

Hereditary

Autoimmunity Anemia

Severe Infection

Elliptocytosis

A condition where RBC appear as ovals

Schistocytes

A condtion where RBC appear fragmented and sheared

What can cause schistocytosis

Microangipathic Hemolysis