Intro to Heme

1/5/26

Hematology def.

study of blood and blood related disorders

What are the roles of blood

• transport O2, nutrients, metabolic waste products

• regulate temp

• immune system support

• hemostasis and circulation of coag. factors

• signal transmission (circulating hormones)

What is the general breakdown of blood and respective %

Plasma 55%; cellular components 45%

What is the breakdown of plasma

90% water; 10% sugar, protein, salt, hormones, Ab, coag. factors

primary function of plasma

maintain fluid balance

what is the breakdown of cellular components (of blood)

erythrocytes, leukocytes, platelets

How can we separate components of blood based on density

centrifuge

Rank components of blood from least dense to most dense

1. plasma

2. buffy coat

3. erythrocytes

What is contained in the buffy coat

WBC and platelets

Hematopoiesis def.

production of cellular components of blood

At what point does hematopoiesis occur in a person’s life?

throughout entire lifetime beginning during first few weeks of life

Where does hematopoiesis occur in utero

yolk sac

Where does hematopoiesis occur as the fetus develops

liver and spleen

Where does hematopoiesis occur in healthy patients

exclusively in bone marrow

What is the purpose of red marrow

major site of hematopoiesis

where do we primarily find red marrow

flat bones

What is yellow marrow

fatty tissue

Is yellow marrow involved in hematopoiesis normally?

no! seen during pathologic states

Where do we find yellow marrow

diaphysis and shaft of long bones

What are 3 regulators of hematopoiesis

1. epo

2. thyroid hormones

3. androgens

What regulator of hematopoiesis is considered the “driving force” needed to stimulate production of RBC

EPO

Where is EPO produced in adults?

Kidneys

How does the body know to release EPO

Kidneys detect low O2

What are 2 key factors about hematopoietic stem cells that promotes survival

1. self renewing

2. multipotent- able to differentiate into different cell types

What is the relationship between EPO and Hematopoietic stem cells

EPO influences differentiation into mature erythrocyte

Finish the chain: stem cell —> common myeloid progenitor cell —> 1 + GM-CSF

—> 2. + TPO

—> 3. + EPO

1. granulocytes

2. platelets

3. RBC

Pathway of stem cell —> RBC

(+) EPO

1. stem cell + EPO

2. proerythroblast

3. erythroblast

4. normoblast

5. reticulocyte

6. erythrocyte

How long is erythropoiesis

7-10 days

Where does majority of erythropoiesis take place

Bone marrow

In what ways does a mature RBC differ from stem cell during early erythropoiesis

1. change shape (biconcave)

2. change size (smaller)

3. anucleated

4. Hgb production (red)

does reticulocyte count come with CBC?

no

Why do we use reticulocyte count

effective marker of erythropoiesis (answers, “are we making RBC?”)

Which cell is bigger: reticulocyte or mature erythrocyte

reticulocyte

What is a normal reticulocyte count

<2.5%

What is the most abundant cell types of all cellular components of blood

erythrocyte

Major function of erythrocyte

transfer O2 to tissue, exchange for CO2

Why do RBC take on biconcave shape

1. increase surface area

2. flexible

3. fits into small capillaries

What is important to note about RBC because they are anucleated

they cannot repair themselves and have limited lifespan

Lifespan of RBC

120 days

Why are RBC red

hemoglobin

RBC contain on average # hemoglobin molecules

270mil

Normal MALE hemoglobin val.

13.5-17.5 g/dL

Normal FEMALE hemoglobin val.

12.0-16.0 g/dL

Function of heme in hemoglobin

bind O2

Function of globin in hemoglobin

surround and protect heme groups for O2 transport; prevent irreversible O2 binding

1 hemoglobin molecule can bind # O2 molecules

1 hemoglobin: 4 O2

1 hemoglobin molecule contains # heme groups

1 hemoglobin: 4 heme groups

Heme groups contain what in center

Iron (Fe2+)

Methemoglobinemia def.

Heme binds ferric iron (Fe3+) and cannot reversibly bind and release O2

Key characteristic of blood presentation in methemoglobinemia

Looks like chocolate

Acquired causes of methemoglobinemia

1. dapsone

2. antimalarial drugs (-quine)

3. topical anesthetics (benzocaine)

Ways to test hemoglobin saturation

ABG & Pulse Ox

ABG: 3 key characteristics about readings/test

1. precise

2. sporadic

3. invasive

Pulse Ox: 3 key characteristics about readings/test

1. Peripheral measurement

2. continuous

3. noninvasive

3 causes falsely normal to high hemoglobin readings

1. carboxyhemoglobin

2. elevated HgA1C

3. Skin pigmentation

3 causes falsely low hemoglobin readings

1. nail polish

2. poor perfusion

3. hemoglobinopathies

Which of the following is NOT an example of a hemoglobinopathy that would cause falsely low readings of hemoglobin

extra glycosylated hemoglobin

Most adult hemoglobin is found as what type?

hemoglobin A

What form of hemoglobin is found in utero

hemoglobin F

What are the 4 subunits of globin

2 alpha, 2 beta

What happens to old or damaged RBC

Phagocytosis via macrophages in spleen and bone marrow

Role of G6PD in RBC

enzyme that resists injury

Reticuloendothelial system def.

careful regulation of RBC lifecycle managed by specialized macrophages in the spleen, liver, and bone marrow

Extravascular hemolysis def.

splenic macrophages breakdown RBC into unit parts of heme/globin

Globin breaks down into… and is sent to

amino acids; bone marrow to make new RBC

Heme breaks down into (2)

1. non-iron portion = porphyrin

2. iron

Porphyrin breaks down into…

biliverdin —> unconjugated bilirubin

Unconjugated bilirubin needs to bind to albumin. Why

It is toxic! Needs to bind so it can be transported to the liver

Why does unconjugated bilirubin go to the liver

becomes conjugated to produce bile

What can we see on a CMP that gives insight to how heme is being broken down?

total bilirubin

Is extravascular or intravascular hemolysis more common

extravascular (90%)

Intravascular hemolysis def.

RBC lysis not done by macrophages within systemic circulation

Can the body handle large amounts of intravascular hemolysis

No

Lactate dehydrogenase (LDH) def.

enzyme found within all living cells; high content in RBC

purpose of Lactate dehydrogenase (LDH)

biomarker of tissue breakdown- can indicate hemolysis

Pseudohyperkalemia def.

false elevation of potassium in blood bc RBC are breaking down in circulation

2 main sources of iron

1. diet

2. recycled from old RBC

What are the controlled mechanisms for excreting excess iron

There are none

Why must iron always be bound in circulation

free iron is toxic

What does the liver produce to bind to iron for safe transport and to increase solubility

transferrin

Iron is stored in the form of?

1. ferritin

2. hemosiderin

What is the primary iron storage

ferritin; 4500 iron ions: 1 ferritin

Do men or premenopausal women have more iron storage

men

4 specific examples of events that alter iron stores

1. menses

2. pregnancies

3. lactation

4. iron intake (diet)