Hematology and Oncology Physiology

• Function:
• -carries O₂ to tissue and CO₂ to lungs
• -membrane contains Cl^-/HCO3^- antiporter (allows RBCs to sequester HCO3^- and transport CO₂ from periphery to lungs for  elimination)

• Structure:
• -anucleate
• -biconcave
• -large surface to volume ratio for gas exchange
• -life span = 120 days

• Source of energy:
• -glucose
• -90% used in glycolysis
• -10% used in HMP shunt

• -polycythemia
• -increased hematocrit

Varying sizes

Varying shapes

• -Immature erythrocyte
• -marker of erythroid proliferation

• Function:
• -primary hemostasis
• -activated by endothelial injury
• -aggregates with other platelets and interacts with fibrin to form platelet plug

• Structure:
• -small cytoplasmic fragment derived from megakarycytes
• -Dense granules (ADP, calcium)
• -α granules (vWF, fibrinogen)

*approximately 1/2 of platelets stored the spleen

*thrombocytopenia and and platelet dysfunction result in petechiae

• Granulocytes:
• -neutrophils
• -eosinophils
• -basophils

• Mononuclear Cells:
• -monocytes
• -lymphocytes

• Function:
• -defense against infection

Normal count = 4000-10,000 cells/mm³

• Neutrophils (54-62%)
• Lymphocytes (25-33%)
• Monocytes (3-7%)
• Eosinophils (1-3%)
• Basophils (0-0.75%)

Neutrophils Like Making Everything Better

• Function:
• -acute inflammatory cell
• -increased in bacterial infections
• -phagocytic

• Structure:
• -multilobed nucleus

• Small, numerous granules:
• -alk phos
• -collagenase
• -lysozyme
• -lactoferrin

• Lysosomes:
• -Large, less numerous
• -azurophilic granules
• -acid phosphatase
• -peroxidase
• -β-glucuronidase

• ->5 lobes
• -seen in vitamin B12/folate deficiencies

• -immature neutrophils
• -reflect states of increased myeloid proliferation (bacterial infection, CML)

• Function:
• -differentiates into macrophages in tissues

• Structure:
• -large, kidney shaped nucleus
• -Extensive "frosted glass" cytoplasm

• Function:
• -phagocytoses bacteria, cell debris and senescent RBCs
• -scavenges damaged cells and tissues
• -long life in tissues
• -activated by IFNg
• -can act as APC via MHC II

• Structure:
• -differentiate from circulating monocytes
• -marker: CD14

• Function:
• -defends against helminthic infections (MBP)
• -highly phagocytic for antigen-antibody complexes
• -produces histaminase and arylsulfatase (helps limit reaction following mast cell degranulation)

• Structure:
• -bilobate nucleus
• -large eosinophilic granules of uniform size

• "NAACP"
• Neoplastic
• Asthma
• Allergic process
• Collagen vascular diseases
• Parasites

• Function:
• -mediates allergic reaction

• Granules:
• -densely basophilic
• -heparin (anticoagulant)
• -histamine (vasodilator)
• -leukotrienes (LTD4)

• Function:
• -mediates allergic reaction in local tissues
• -involved in Type I hypersensitivity
• -can bind Fc portion of IgE to membrane
• -IgE cross-links upon antigen binding causing degranulation

• Structure:
• -resemble basophils structurally and functionally

• Granules:
• -histamine
• -heparin
• -eosinophil chemotactic factors

• Function:
• -highly phagocytic APCs
• -link between innate and adaptive immune system

• Structure:
• -express MHCII and Fc R on surface
• -called Langerhans cells in skin

• Function:
• -mediates adaptive immunity
• -B cells and T cells

• Structure:
• -round, densely staining nucleus
• -small amount of pale cytoplasm

• Function:
• -part of humoral immune response
• -can act as APC via MHC II

• Development:
• -arises from stem cells in bone marrow
• -matures in marrow
• -migrates to peripheral lymphoid tissue (follicles of LN, white pulp of spleen, unencapsulated lymphoid tissue)
• -differentiate in plasma cells when encounter antigen

• Function:
• -produces large amounts of antibody specific to a particular antigen

• Structure:
• -off center nucleus
• -clock-face chromatin distribution
• -abundant RER
• -well-developed golgi

**neoplasm = multiple myeloma

• Function:
• -mediates cellular immune response
• -majority of circulating lymphocytes (80%)

• Development:
• -originates from stem cell in the BM
• -matures in the thymus
• -T cells differentiate into cytotoxic cells, helper cells and regulatory T cells
• -CD28 costimulation is necessary for T cell activation

• A
• B
• AB
• O
• Rh

• Antigen on RBC: A
• Antibody in plasma: anti-B (IgM)

• Antigen on RBC: B
• Antibody in plasma: anti-A (IgM)

• Antigen on RBCs: A and B
• Antibody in plasma: None

• -Universal recipient of RBCs
• -Universal donor of plasma

• Antigen on RBCs: Neither A or B
• Antigen in plasma: anti-A and anti-B

• -universal donor of RBCs
• -universal recipient of plasma

Antigen on RBCs: Rh antigen

RH- mothers exposed to fetal Rh+ blood (often during delivery) may make anti-Rh IgG

In subsequent pregnancy anti-Rh IgG cross the placenta causing hemolytic disease of the new born (erythroblastosis fetalis) if the next fetus is Rh+

• Treatment:
• -Rho(D) Ig form mother at first delivery to prevent initial sensitization of Rh- mother to Rh antigen

• -"lucky pathway" (only have to remember two)
• Factors:
• -Tissue Factor (TF)
• -VII

• Test:
• -PT (less numbers, less letters)

-"unlucky pathway"

• Factors:
• -XII
• -XI
• -IX
• -VII

• Test:
• -PTT (more numbers, more letters)

• 
• Fibrin monomer Aggregation:
• -requires Ca2+ and XIIIa

"Small dollar bills"

• Factors:
• -I
• -II
• -V
• -X

• Tests:
• -PT and PTT

• Plasminogen:
• -plasmin breaks down fibrin
• -activated by t-PA, U-PA

• Inhibition of Fibrinolytic system:
• -TAFIa (shields fibrin from degradation, activated by thrombin/TM)
• -PAI-1 (inhibits t-PA)

• 
• Vitamin K dependent factors:
• -II
• -VII
• -IX
• -X
• -Protein C
• -Protein S

• **VIII is not produced in liver and is protected by vWF
• Deficiency:
• -Warfarin inhibits epoxide reductase
• -neonates lack enteric bacteria that produce vitamin K

• 
• Protein C
• -activated by thrombomodulin
• -works with Protein S to inactivate Va, VIIIa

• Antithrombin
• -inhibits activated forms of II, VII, IX, X, XI, XII
• -inactivated by heparin

= platelet plug formation

**Transient vasoconstriction

• 1. Injury
• -vWF binds exposed collagen upon endothelial damage

• 2. Platelet Adhesion
• -platelets bind vWF via GpIb receptor at site of injury
• -platelets release ADP and Ca²⁺ (necessary for coagulation cascade)
• -ADP helps platelets adhere to endothelium

• 3. Platelet Activation:
• -ADP binding induces GpIIb/IIIa expression on platelet surface

• 4. Platelet Aggregation
• -Fibrinogen binds GpIIb/IIa and links platelets
• -temporary plug stops bleeding

• -TXA₂ (released by platelets)
• -decreased blood flow

• -PGI2 and NO (released by endothelial cells)
• -increased blood flow

• Diseases:
• vWF deficiency: von Willebrand's disease
• GpIb deficiency: Bernard Soulier syndrome
• GpIIb/IIIa deficiency: Glanzmann's thrombasthenia

• Drugs:
• ADP receptor blocked by (inhibit GpIIb/IIIa expression): clopidogrel and ticlopidine
• GpIIb/IIIa blocked by: abciximab
• COX inhibited by (decreased TXA2 synthesis): ASA

Acute phase reactants in plasma (eg: fibrinogen) can cause RBC aggregation and increase ESR

• Elevated ESR:
• -infections
• -autoimmine diseases (SLE, RA, temporal arteritis)
• -malignancy
• -GI disease (UC)
• -pregnancy

• Decreased ESR:
• -polycythemia
• -SCA
• -CHF
• -microcytosis
• -hypofibrinogenemia