Heme

erythrocyte

Nonnucleated disk w/ hemoglobin

Function: tranport gas to and from the lungs/tissues

Life span: 80-120d

granulocytes

Leukocyte classification

• Consists of: neutrophils, eosinophils, basophils, & mast cells

• Have membrane-bound granules in their cytoplasm

• involved in inflammatory/immune functions

agranulocytes

Leukocyte classification

• Lymphocytes

• NK cells

• Monocytes

• Macrophages

• Dendritic cells

platelets

Irregularly shaped cytoplasmic fragment

Function: hemostasis, coagulation/clot formation, release of growth factors

Life span: 8-11d

thymus

Upper chest, between lungs and behind breast bone

Role: T cell maturation and hormone production (thymosin, thymopoietin, and thymulin)

bone marrow

Red (active) and yellow (inactive) bone marrow

Role: Hemapoesis

Niches provide for hematopoietic stem cells and allow them to differentiate into myeloid or lymphoid cells

secondary lymph organs

• Spleen - near stomach

• Lymph nodes

• Tonsils - back of mouth

• Peyer patches - small intestine

Location

intrinsic pathway

Clotting pathway

• Activated when blood comes into contact w/ collagen / anionic surfce. Ex. exposure of subendothelial collage d/t BV damage, HD cath/ECMO clotting (contact activation pathway)

• Defense mechanism against foreign proteins, pathogens, and artificial materials

• Factor XIIa recruits HK that is complexed w/ PK

• PK (prekallikrein) changes into kallikrein that generates more factor XIIa, amplifying the pathway

• HK releases bradykinin

• XI/XIa

• IX → X

• Leads into common pathway

• Minutes (slower)

• Tests: PTT

• Not really needed for hemostasis

hageman factor (XII)

Function: XIIa activates factor XI

Initiates the intrinsic clotting pathway

extrinsic pathway

Clotting pathway

• Activated by vascular injury - tissue thromboplastin/tissue factor (TF)

• TF binds w/ VII to initiate pathway

• Factor X is activated

• Leads into common pathway

• Fast - seconds

• Tests: PT, INR

tissue thromboplastin (tissue factor)

Located in vascular subendothelium, activated that extrinsic clotting pathway

common pathway

Clotting pathway

• where the extrinsic and intrinsic pathways converge

• starts with the activation of factor X

• Xa activates prothrombin (factor II)

• Thrombin converts fibrinogen to fibrin

• Fibrin forms clot mesh

• Fibrin activates factor XIII which cross links the strands

• Speed: depends

• Tests: PT

hemostatic control mechanisms

Endothelium produces these to prevent spontaneous clot formation:

• Nitric oxide (NO)

• Prostacyclin I2 (PGI2)

• Thrombin inhibitors (antithrombin III)

• Tissue factor inhibitors

• Degrading activated clotting factors (thrombomodulin-protein C)

PGI2

anticoagulation control mechanism

• prostacyclin I₂

• Produced by the endothelium

• vasodilator

• maintain platelets in an inactive state

antithrombin iii

anticoagulation control mechanism

• Produced by the endothelium

• produced by the liver

• binds to heparin sulfate on the surface of endothelial cells

• these complexes inhibit thrombin and other activated clotting factors

tissue factor inhibitors

anticoagulation control mechanism

• tissue factor pathway inhibitors

• Produced by the endothelium

• primary inhibitor of the initiation of blood clotting

• forms complexes w/ factor Xa and inhibits the extrinsic pathway

thrombomodulin-protein c

anticoagulation control mechanism

• complex

• acts in association w/ protein S

• Degrades factors Va and VIIIa

• Inhibits fibrin formation

plasminogen

Part of the fibrinolytic system

• converted to plasmin by tissue plasminogen activator (tPA) or urokinase-like plasminogen activator (uPA)

• activated by thrombin, fibrin, factor XIIa, factor XIa, and kallikrein

plasmin

Part of the fibrinolytic system

• an enzyme made by the conversion of plasminogen via tPA or uPA

• degrades the clot

urokinase plasminogen activator

Part of the fibrinolytic system

• involved in extravascular fibrinolysis

• converts plasminogen to plasmin

tissue plasminogen activator

Part of the fibrinolytic system

• involved in intravascular fibrinolysis

• converts plasminogen to plasmin

fibrin degradation products

End products of fibrinolysis, can be measured clinically

ex. D-dimer

polycythemia

Morphology, symptoms, lab results, treatment

Type of myeloid malignancy, bone marrow makes too many red blood cells

• presence of Janus kinase 2 gene (JAK2gene)

• causes increased intracellular stimulation of cell division and overproduction

iron overload

Can be primary or secondary, primary is most commonly hereditary hemochromatosis

• caused by excess iron absorption due to a deficiency of hepcidin/decreased binding of hepcidin to ferroportin

• iron tissue deposits

iron-deficiency anemia

Color: hypochromic

Morphology: microcytic

Symptoms: Pallor, fatigue, SOB, brittle nails, red, sore tongue, angular stomatitis

Lab results: low H&H, MCV, MCHC, ferritin

Treatment: iron supplementation

sideroblastic anemia

Dysfunctional iron uptake by erythroblasts

Color: hypochromic

Morphology: microcytic

Symptoms: iron overload, splenomegaly, hepatomegaly, bronze skin

Lab results: bone marrow examination, normocytic and normochromic cells w/ some microcytic hypochromic cells on smear, rigid sideroblasts

Treatment: reduce iron overload, remove triggers (ex. alcohol), chelation therapy, stem cell transplant

pernicious anemia (vitamin b12 deficiency anemia)

Causes by vitamin b12 deficiency d/t lack of intrinsic factor

Color: normochromic

Morphology: macrocytic

Symptoms: weakness, fatigue, paresthesia, loss of appetite, glossitis, sallow skin (pallor + jaundice), hepatomegaly, splenomegaly

Lab results: high MCV, normal MCHC, low H&H, low b12 levels

Treatment: b12 replacement

anemia of chronic disease

d/t decreased erythrocyte lifespan, decreased erythropoietin, ineffective bone marrow, altered iron metabolism

Color: normochromic

Morphology: normocytic

Symptoms: fatigue, brittle nails, red, sore tongue, angular stomatitis

Lab results: depends on cause, high total body iron storage and failure to respond to conventional iron replacement

Treatment: treat cause

acute blood loss anemia

Color: normochromic

Morphology: normocytic

Symptoms: HoTN, tachycardia, tachypnea, pallor

Lab results: low H&H

Treatment: stop the bleed, transfusion

folate deficiency anemia

Common in alchoholics and those w/ chronic malnourishment

Color: normochromic

Morphology: macrocytic

Symptoms: weakness, paresthesias, loss of appetite, wt loss, sore beefy tongue, sallow skin, nerve symptoms

Lab results: low H&H, low folate

Treatment: folate replacement

hemolytic anemia

d/t destruction of RBCs, can be from paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemias, and drug induced

Color: abnormal cell shape

Morphology: abnormal cell shape

Symptoms: jaundice, splenomegaly

Lab results: low H&H, bone marrow biopsy

Treatment: corticosteroid, splenectomy, rituximab, eculizumab (paroxysmal nocturnal hemoglobinuria)

aplastic anemia

Color: normochromic

Morphology: normocytic

Symptoms: hypoxemia, pallor, weakness along w/ fever and dyspnea

Lab results: bone marrow biopsy, pancytopenia

Treatment: bone marrow/stem cell transplant, immunosuppression, corticosteroids

neutrophilia

causes

• bacterial infections

• acute inflammation

• physical/emotional stress

neutropenia

causes

• prolonged, severe infection

• decreased production

• congenital

• acquired (hodgkin/non-hodgkin lymphoma, leukemias, aplastic anemia, megaloblastic anemias)

eosinophilia

causes

• hypersensitivity reactions

• parasitic invasions

eosinopenia

causes

• migration of cells to inflammatory sites

• stress

• shock

• trauma

• surgery

• burns

basophilia

causes

• hypersensitivity reactions

• immune reactions

• CML

basopenia

causes

• acute infections

• hyperthyroidism

• long-term steroid therapy

• endocrine disorders

monocytosis

causes

• usually occurs w/ neutropenia in late stage bacterial infections

• chronic infections

• correlates w. extent of myocardial damage

monocytopenia

causes

• has been seen w/ hairy cell leukemia and prednisone treatments

• not much is known

infectious mononucleosis

Self-limiting viral infection of B lymphocytes

causes: EBV

infectious period: 4-8wks incubation, 3-5d prodromal

acute lymphocytic leukemia (ALL)

Progression: rapid

Adults or children: children (mc form)

Any special cells: greater than 30% lymphoblasts and B cells

Survival: 91%

acute myelogenous leukemia (AML)

Progression: rapid

Adults or children: adults (mc form)

Any special cells: precursor myeloid cells

Survival: 24%

chronic myelogenous leukemia (CML)

Progression: slow

Adults or children: mostly adults

Any special cells: neutrophilic or eosinophilic or clonal, arise from a hematopoietic stem cell

Survival: no cure

chronic lymphocytic leukemia (CLL)

Progression: slow

Adults or children: adults

Any special cells: monoconal B cells

Survival: 85%

hodgkin lymphoma

Progression: localized, orderly spread

Symptoms: fever, night sweats, wt loss, lymphadenopathy, mediastinal mass

Any special cells: Reed-Sternberg cells, B lymphocytes

Survival: 87%–89%

non-hodgkin lymphoma

Progression: noncontiguous spread, multiple peripheral nodes

Symptoms: painless lymphadenopathy, retroperitoneal and ABD masses, ascites

Any special cells: B cells, T cells, or NK cells

Survival: 74%

burkitt lymphoma

Progression: highly aggressive, fast growing

Symptoms: Tumor of jaw and facial bones, ABD swelling

Any special cells: B cells

Survival: 90% in children and 50–90% in adults

lymphoblastic lymphoma

Progression: quick

Symptoms: painless lymphadenopathy in the neck

Any special cells: T cells

Survival: 5-year overall survival (OS) often exceeding 80–90% in children and roughly 65–70% in adults

multiple myeloma

Progression: originating from abnormal plasma cell growth in the bone marrow. It evolves from asymptomatic, low-level plasma cell protein production to an aggressive, symptomatic cancer causing bone destruction, anemia, and kidney failure.

Causes: plasma cell neoplasia, risk factors include obesity, agent orange, radiation

Symptoms: hypercalcemia, renal failure, anemia, lytic lesions (“punched out” regions of bone), skeletal pain, hyperviscosity syndrome, recurring infections

Any special cells: plasma cells, Bence Jones proteins

waldenstrom macroglobulinemia

(lymphoplasmacytic lymphoma)

Progression: slow-growing plasma cell tumor that secretes IgM

Causes: acquired, non-inherited genetic mutations in B-lymphocyte white blood cells

Symptoms: weakness, fatigue, bleeding, wt loss, bruising

Any special cells: IgM

leukocyte

nucleated cell

Function: body defense mechanisms

Life span: varies by subtype

neutrophil

Segmented polymorphonuclear granulocyte

Function: phagocytosis, esp during early phase of inflammation

Life span: 4d

eosinophil

Segmented polymorphonuclear granulocyte

Function: control of inflammation, phagocytosis, defense against parasites, & allergic reactions

Life span: 8-12d

basophil

Segmented polymorphonuclear granulocyte

Function: Mast cell-like, associated w/ allergic reactions

Life span: few hrs to days

monocytes (macrophage)

Large mononuclear phagocyte

Function: phagocytosis, mononuclear phagocyte system

Life span: months or years

lymphocyte

Mononuclear immunocyte

Function: humoral and cell-mediated immunity

Life span: days or years depending on type

natural killer cells

Large granular lymphocyte

Function: defense against some tumors and viruses

Life span: unknown

intrinsic

If you see just an abnormal PTT, which pathway is effected?

extrinsic/common

PT/INR

common lymphoid progenitors

type of leukocyte progenitor cell:

• some remain in bone marrow

• others undergo differentiation into B cells

common myeloid progenitors

type of leukocyte progenitor cell:

• differentiate into:

  • basophils

  • mast cells

  • eosinophils

  • megakaryocytes

  • granulocyte/monocyte progenitors

NO

anticoagulation control mechanism

• nitric oxide/endothelium-derived vasorelaxant factor

• Produced by the endothelium

• vasodilator

• maintain platelets in an inactive state

polycythemia symptoms

Symptoms:

• increased red cell mass & Hct

  • thrombosis

  • ischemia

• plethora (ruddy, red color of the face, hands, feet, ears, and mucous membranes)

• engorged retinal and cerebral veins

  • HA, drowsiness, delirium, mania, psychotic depression, chorea, visual disturbances

• Splenomegaly

• ABD pain

• Intense, painful itching that seems to be intensified by heat/exposure to water

polycythemia labs

Labs:

• Hgb >16.5 g/dL or Hct >49%

• moderate increases in WBCs and platelets

• JAK₂ mutation

• decreased erythropoietin

polycythemia treatment

Treatment:

• phlebotomy (300-500mls at a time “blood letting”)

• low dose ASA

iron overload symptoms

Symptoms:

• fatigue

• arthralgias (d/t iron deposits)

• weakness

• wt loss

• cirrhosis

• URQ pain

• HF symptoms

conjugated

Which form of bilirubin (conjugated or un-conjugated) is water soluble and therefore can be excreted?

transferrin

a liver-produced protein that transports iron through the blood to tissues, crucial for red blood cell formation

hepcadin

regulates iron

CML and ALL

forms of leukemia that are associated with the Philadelphia chromosome

Thrombopoietin and IL-11

What two things maintain leukocyte levels?

inhibit (_)

Proteins C and S ___ factors Va and VIIIa

RBC

Vitamins C and B and iron are needed for the production of…

bone marrow

Where is the disease in leukemia?

vwf (von willebrand factor)

What is released by endothelial cells when damaged to cause platelet adhesion?

Platelet activation (?)

What happens after platelets bind with vWF and bind in the damaged area?

activation

Causes platelets to change shape, increase surface area, and degranulate

TXA2

Counters the effects of PGI2 to promote clotting during platelet plug formation

ADP

Released by platelet granules to recruit more platelets to form platelet plug

factors III and VII

What factors are part of the extrinsic pathway before activating factor X?

factors XII, XI, IX, and VIII

What factors are part of the intrinsic pathway before activating factor X?

factors X, V, II, I, and XIII

What clotting factors are part of the common pathway?