The Hematologic System

different function of blood

- transporting oxygen

- forming blood clots

- carrying cells and antibodies

- bringing waste to kidney and liver

- regulating body temp

four main components of blood

plasma

red blood cells

white blood cells

platelets

plasma info

- 55% total volume of blood

- electrolytes, waste, proteins, glucose, antigens, formed elements, and clotting factors

role of plasma

transport of...

- blood cells

- waste

- antibodies

- clotting proteins

- chemical messengers

- electrolytes

plasma vs. serum

plasma - clotting factors = serum

erythrocytes info

- most abundant

- tissue oxygenation

- contain hemoglobin

- biconcavity and reversible deformity

- do not contain nucleus

- 120 day life cycle

leukocytes

- defend body against infection

- granulocytes

- agranulocytes

what are granulocytes?

- "phagocytes"

- neutrophils, basophils, and eosinophils

- contain many granules (store molecules)

What are arganulocytes?

monocytes, lymphocytes, and macrophages

platelet info

- cellular fragments of megakaryocyte

- incapable of mitotic division

- granules are generally pro-inflammatory

- live for 8-11 days

- no nucleus

- most in circulation, some in spleen

platelets are removed by the...

spleen

normal count of platelets

140,000-340,000 platelets/mm3

normal level of leukocytes

5000-10,000 cells/mm3

lymphoid organs link the...

hematologic and immune systems

primary lymphoid organs

thymus: T-cell is created in bone marrow but must mature in thymus

bone marrow

secondary lymphoid organs

- spleen

- lymph nodes

- tonsils

- peyer patches of small intestine

spleen information

- largest secondary lymphoid organ

Functions:

- fetal hematopoiesis

- filters blood

- immunity to blood borne pathogens

- destroys aged erythrocytes

- blood reservoir for leukocytes

-stores iron

lymph nodes information

- development and activity of lymphocytes, monocytes, and macrophages (argranulocytes)

- filter lymph

- fibrous capsules

- first encounter between antigen and lymphocyte

what is hematopoiesis?

blood cell production

- done in bone marrow for adults and spleen for fetus

humans need ______ new blood cells per day

100 billion

two kinds of stem cells

1.) mesenchymal cells (MSC): stromal cells

2.) hematopoietic cells (HSC): hematologic progenitors

pluripotent vs. multipotent

pluripotent: cells have unlimited differentiation potential

multipotent: more limited differentiation abilities

heamtopoietic stem cells differentiate under the control of _____

cytokines and growth factors

purpose of colony stimulating factors

they are a growth factor

- push cells down specific different lineages

what are the two pools of hematopoiesis

stem cell pool and bone marrow pool

4 CSF and which cell do they proliferate?

GM-CSF = granulocyte macrophage CSF

G-CSF = granulocyte CSF

SCF = stem cell factor

M-CSF = macrophage CSF

myeloid stem cells

blood stem cells can proliferate into...

myeloid stem cell or lymphoid stem cell

erythropoietin leads to

EPO ----> erythroblast ----> reticulocyte ----> RBC

thrombopoietin leads to

TPO ----> megakaryocyte ----> platelet

why and where is EPO secreted

why: tissue hypoxia

where: kidney

which part of kidney produces EPO?

peritubular cells

two main functions of RBC

- oxygen transportation

- chemokine mop

normal RBC characteristics

- uniform size and shape

- diameter about the size of lymphocyte nucleus

- center pallor = 1/3 diameter of RBC

what is the most common general blood disorder?

anemia

what causes anemia?

decrease in hemoglobin

ferritin info

- major iron storage protein

- precursor is apoferritin (without iron)

transferrin info

- transfers iron in circulation

- precursor apotransferrin

iron homeostasis is controlled by the hormone...

hepcidin

iron cycle

1.) hemoglobin is removed from old erythrocyte

2.) heme is broken down into iron and bilirubin

3.) transferrin plus iron is stored in spleen or directly put into bone marrow

4.) spleen released transferrin and iron into bone marrow to restart hematopoeisis

senescent erythrocytes

- can no longer replicate and survive

- macrophages remove them from circulation

- often broken down in the spleen

what occurs if spleen is unavailable for senescent erythrocytes?

Kupffer cells remove older RBS in liver

what activates platelet degranulation?

- thrombin

- ADP

- collagen

- platelet activating factor (PAF)

three phases of primary hemostatsis

1.) platelet adhesion

2.) platelet activation

3.) platelet aggregation

platelet adhesion info

- receptors of the integrin family

- vWF is released by endothelial cells to show where platelet should bind

- other receptors promote platelet activation

what is vWF

von Willebrand factor: present in plasma and released by endothelial cells and activated platelets

GPIIb/IIIa

- most abundant platelet aggregation receptor

- for platelet to platelet connection

- connect via fibrinogen bridge

GP Ib

- attach to vWF for platelet plug formation

types of degranules

Dense granules

Alpha granules

what is the first step in the shared clotting cascade pathway?

activation of factor X to Xa

two pathways that lead to conversion of prothrombin to thrombin

intrinsic: damage to the blood vessel

extrinsic: damage to tissue outside of vessel

three test to asses coagulation process

1.) bleeding time

2.) prothrombin time (INR)

3.) partial thromboplastin time (PTT)

bleeding time tests the...

platelet function (incision on underside of forearm)

drugs such as ___ increase the bleeding time

aspirin

prothrombin time (PT) evaluates the...

extrinsic coag pathway (blood plasma in presence of excess Ca2+)

_____ increases the prothrombin time (extrinsic pathway)

warfarin

partial thromboplastin time (PTT) tests the...

intrinsic pathway

PTT helps specifically test for...

hemophilia A (classic) and hemophilia B (Christmas disease)

hemophilia A/B info

- X-linked recessive disorder

- result in deficiency of clotting factors VIII and IX

types of anticoagulant factors

- tissue factor pathway inhibitor (TFPI)

- antithrombin III

- thrombomodulin

- proteins C and S

- heparin

tissue factor pathway inhibitor (TFPI) info

- anchored to the endothelial cell membrane

- blocks action of FACTOR VII in extrinsic pathway

antithrombin III info

- binds to activated factor X and thrombin

thrombomodulin info

- binds to thrombin

protein C and S info

- act together to inactivate activated factors V and VIII

heparin info

- released from mast cells and basophils

- augments the effects of antithrombin III

antiplatelet drugs

- aspirin and NSAIDs

- ticlopidine

- clopigogrel (Plavix)

- eptifibatide (Integrilin)

aspirin and NSAIDs MOA

inhibit production of thromboxane A2 (platelet activator) by blocking COX

clopidogrel (Plavix) and ticlopidine (Ticlid) MOA

antagonize action of ADP

Eptifibatide (Integrilin)

competitive inhibitor of GP IIb/IIIa

bacterial infections are normally associated with...

increased neutrophils and monocytes

viral infections increase the...

proportion of lymphocytes

leukopoiesis is under the control of...

several cytokines (CSF)

_______ mature in the bone marrow

granulocytes

____ and ____ are released into the bloodstream BEFORE they fully mature

agranulocytes and monocytes

leukocytes increase in response to...

infection

presence of steroids

reduction or depletion of reserves

the ______ has a horseshoe shaped nucleus

monocyte

once activated the ________ cytoplasm grows

lymphocyte

neutrophils structure

- multi-lobular nucleus

- granules stain neutral

eosinophil structure

- bi-lobed nucleus

- stain pinkish-red

basophil structure

- 2 or 3 lobed (S shaped) nucleus

- stain deep blue/purple

neutrophil information

- most abundant granulocyte

- contain microbicidal enzymes (aid in killing bacteria)

- first line of defense

- live 8 hours

- both immature (band cells) and mature can be seen in blood during infection

eosinophils information

- contain digestive enzymes that are effective against parasitic worms

- involved in asthma and allergic reactions

basophils

- store histamine and heparin (anticoag)

- hypersensitivity reactions

- 0.01 to 0.03% of total WBC

______ are increased in myelogenous leukemia

basophils

mast cell info

- highly similar to basophils (histamine)

- central cells in inflammation

- found in vascularized connective tissue

mononuclear phagocyte system (MPS)

- made up of monocytes and macrophages

- main line of defense against bacteria in blood

- found in tissue and lymphoid organs

_______ are the precursor to _______ and ______ cells

monocytes; macrophage; dendritic

macrophages info

- main job: phagocytosis

- remove old cells from circulation

- antigen processors and presenters

- initiate wound healing

dendritic cells

- extend dendrites into tissue for sweep up antigens

- antigen processors and presenters (very efficient due ot dendrites)

B cell info

- only cell to synthesize antibodies

- specialize in certain antigens

* very picky bc they are very potent

T cell info

- even more specific than B cells

- participate in specific immune response

aging and the hematologic system

- changes little

- RBC replaced more slowly

- platelet adhesions increase

- lymphocyte function decreases

- T-cell function declines

- humoral immune system is less responsive

what are possible causes that slow down RBC replacement with age?

- iron depletion

- decreased total serum iron, iron-binding capacity, and intestinal iron absorption

hemosiderin

insoluble form of iron, occurs when there is iron overload

when there is high hepcidin then is _________

low iron in the blood