USMLE Step 1 Hematology

What transporter is found on Erythrocytes and what is the function?

HCO3-/Cl- antiporter

HCO3- leaves the RBC and Cl- moves into RBC (chloride shift)

Source of energy for RBC and how is it used?

GLUCOSE

- 90% in glycolysis

- 10% in HMP shunt

Platelets

a. Life span

b. Function

c. Where are they stored?

a. 8-10 days

b. Primary hemostasis (forms platelet plug by aggregating and sticking to fibrinogen)

c. Spleen (1/3 of them are there)

Granules of Platelets contain

Dense granules: ADP, Ca+2. TXA2

alpha granules: vWF, Fibrinogen

Thrombopoietin

a. Made where?

b. Function

a. Liver and kidney

b. Causes megakaryocytes to proliferate/differentiate and make platelets

vWF receptor on platelet

Gp Ib

Fibrinogen receptor on platelet

Gp IIb/IIIa

Thrombocytopenia results in ____.

Petechiae

Neutrophilic specific granules contain what?

ALP (alkaline phosphatase)

Lysozyme

Collagenase

Lactoferrin

Neutrophilic Lysosomes contain what?

Myeloperoxidase

Beta-glucuronidase

Acid phosphatase

Proteinases

Neutrophilic chemotactic agents

C5a

LTB4 (leukotriene)

IL-8

Platelet-activating Factor (PAF)

Kalikrein

Band Cells have decreased _____ receptors.

Fc receptors (CD16)

Hyper segmented PMNs are seen in ______.

B12/Folate deficiency

Increased band cells are seen in _____.

Myeloid proliferation

Causes of neutrophilia

- Leukocyte adhesion deficiency

- Corticosteroid use

- Acute bacterial infections

- Tissue necrosis

Agranulocytosis

a. What is it?

b. Etiology

c. S/S

a. Extremely low neutrophil count (near absent) w/ normal Hb and platelet count

b. (Agranulocytosis Certainly Causes Pretty Major Collapse To Defense Cells)

- Clozapine

- Colchicine

- Propythiouracil

- Methimazole

- Chloramphenicol

- Ticlopidine

- Dapsone

- Carbamazepine

c.

- Necrotizing ulcers in mouth and throat

- Increased risk of life-threatening infections

Inherited Neutrophil Abnormalities

- Leukocyte adhesion deficiency

- Chronic Granulomatous Disease

- Myeloperoxidase Deficiency

- Chediak-Higashi Syndrome

Function of Eosinophils

- Defend against helminthic infections by secreting Major Basic protein (helminthotoxin)

- Regulates immediate type hypersensitivity reactions by releasing histaminase to inactivate histamine and leukotrienes

Causes of Eosinophilia

(NAACP)

- Neoplasia (hodgkin lymphoma due to increased IL-5)

- Allergies/Asthma

- Addison's Disease, Athero-embolic Disease

- Chronic adrenal insufficiency, Collagen Vascular Disease

- Parasites (invasive)

Function of Basophils

Mediate allergic reactions

What do Basophils secrete?

- Histamine (in granules)

- Heparin (in granules)

- Leukotrienes (synthesize on demand)

Causes of Basophilia

- CML ****

- Hypersensitivity reactions

Types of Lymphocytes

B cells

T cells

NK cells

What do lymphocytes produce?

Hematopoietic growth factors

Causes of lymphocytosis other than cancer.

- Viral infections (CD8 T cells)

- Bacterial infections (esp pertussis)

B cells differentiate into what?

Plasma cells

Memory cells

B cells antigen-present via MHC ___.

II

B cells originate in the _____ and mature in the ____.

Bone marrow

Bone marrow

B cells, after maturation, migrate to...

- Cortex of Lymph node follicles

- Spleen (white pulp)

- Unencapsulated lymphoid tissue

What surface markers do B-cells express?

CD 19

CD 20

CD 21

What organelles are well-developed in plasma cells?

RER

Golgi apparatus

What is the name for the cancer of plasma cells?

Multiple Myeloma

T cells originate in the _____ and mature in the ____.

Bone marrow

Thymus

What surface marker do all T-cells express?

CD3

What co-signal is necessary for T-cell activation

CD28

T cells, after maturation, migrate to...

- Paracortex in lymph node follicles

- Periarterial sheath in spleen

Monocytes on peripheral blood smear look like what?

Large kidney-shaped nucleus

Macrophages antigen-present via MHC ___.

II

Macrophages are activated by..

Gamma-interferon

_____ from bacterial LPS binds to _____ on macrophages to initiate ______.

Lipid A

CD14

Septic shock

Mast cells mediate ....

Allergic reactions

Mast cells bind _______ which causes ________ leading to the release of ____.

1. IgE

2. Degranulation

3.

- Histamine

- Heparin

- Eosinophil Chemotactic factors

Mast cells contain ________ (eosinophilic/basophilic) granules and originate from _____.

Basophilic

Same precursor as basophils

________ prevents mast cell degranulation.

Cromolyn Sodium

Dendritic cells antigen-present via MHC ___.

II

_____ are a link between the innate and adaptive immune systems.

Dendritic cells

Dendritic cells are called _____ in the skin.

Langerhans Cells

_____ antibodies are made in ABO classification. ____ are made in Rh classification

1. IgM

2. IgG

A Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. What will cause hemolytic reaction in these patients

a. A

b. Anti-B (IgM)

c. B blood, AB blood

B Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. What will cause hemolytic reaction in these patients

a. B

b. anti-A (IgM)

c. A blood, AB blood

AB Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. What will cause hemolytic reaction in these patients

a. A and B

b. NONE

c. Nothing

O Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. What will cause hemolytic reaction in these patients

a. NONE

b. Anti-B, Anti-A

c. All blood types other than O

_______ is considered universal donor blood.

O blood

_______ is considered universal recipient patients for blood

AB patients

_______ is considered universal donor of plasma.

AB patients plasma

_______ is considered universal recipient patients for plasma.

O blood patients

______ crosses the placenta. _______ doesn't cross the placenta.

IgG crosses

IgM doesn't

Rh(+) Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. Clinical Relevance

a. Rh (D)

b. None

c. No issues

Rh (-) Blood

a. Group antigens on RBC surface

b. Antibodies in plasma

c. Clinical Relevance

a. None

b. Anti-D (IgG)

c. If mother is exposed to Rh(+) fetal blood during delivery, her body will start making Anti-D IgG which will result in hemolytic disease of newborn if her next pregnancy is w/ an Rh+ fetus. To prevent this formation of Anti-D IgG, mom is given Rh(D) immunoglobulin that can bind the fetal blood from first pregnancy before her body makes Anti-IgD

In Hemolytic Disease of Newborn, What happens?

Mom's Anti-D IgG crosses the placenta and "attacks" fetus in utero

Prevention of Hemolytic Disease of Newborn?

Administer RhoGAM to Rh (-) pregnant women during 3rd trimester/after each pregnancy to prevent anti-Rh IgG formation

- RhoGAM is a anti-D IgG

Primary Hemostasis

a. What is it?

b. What initiates it?

c. What are the components?

a. Platelet plug formation (weak) at site of injury

b. Vascular injury (exposure of collagen, basement membrane)

c.

- Since blood vessel is anti-coagulant surface, any disruption is possible for clot formation

- Platelets form a plug at injured site

vWF

a. Function

b. Produced by?

a. Acts as a linker molecule for platelets to bind to during plug formation

b.

- Alpha granules of platelets

- Weibel-Palade bodies of endothelial cells

Weibel-Palade bodies of endothelial cells contain what?

- vWF

- P-Selectin

Endothelin

Released by damaged endothelial cells

- Causes vasoconstriction

ADP

a. Function

b. Produced by?

a. Binds platelets and increases platelet expression of Gp IIb/IIIa

b. In granules in platelets

Gp IIb/IIIa

Platelet receptor that binds fibrinogen which is necessary for platelet aggregation

Steps of Plug Formation

1. Injury to endothelium causes transient vasoconstriction mediated by Endothelinand neural stimulation reflex

2. vWF binds to exposed sub endothelial collagen

3. Platelet binds to vWF via Gp Ib and undergoes conformational change and degranulation releasing ADP, Ca+2, TXA2

4. ADP binds Platelet, increases Gp IIb/IIIa expression

5. Fibrinogen binds Gp IIb/IIIa and links platelets for aggregation

Aggregation is mediated by ______ resulting in _____ blood flow.

TXA2

decreased

Anti-Aggregation is mediated by ______ resulting in _____ blood flow.

NO and PGI2

Increased

Secondary Hemostasis

a. Initiated by

b. Function

a. Activated platelets

b. Produce fibrin to stabilize platelet plug (fibrin can be cross linked)

Coagulation Factors

Produced in liver in an inactivated state

What activates coagulation factors?

Ca+2

Phospholipid surface (platelet)

Hageman Factor

Coagulation factor activated by sub endothelial collagen

Vitamin K Dependent Factors

2, 7, 9, 10

Protein C

Protein S

Coagulation Cascade

Thrombin

- End product of coagulation cascade

- Activated Prothrombin

- Converts fibrinogen to fibrin

Anti-Coagulants

- Anti-thrombin

- Heparin

- tPA

- Protein C

- Protein S

Anti-Thromibin

- Inhibits activated forms of factors 2, 7, 9 ,10, 11, 12

- Targets Thrombin and Factor Xa

Heparin

Enhances the activity of anti-thrombin

tPA

Used clinically as a thrombolytic

- Converts plasminogen to plasmin

Protein C and Protein S

Activated Protein C and Protein S cleave and inactivate Factors 5a and 8a

Plasmin

- Anti-coagulant

- Cleaves cross-linked fibrin and serum fibrinogen

- Destroys coagulation factors

- Blocks platelet aggregation

_____ inactivates Plasmin.

Alpha-2 Anti-Plasmin

vitamin K metabolism

Requires glutamate!

Kinin Cascade

How is HMWK important for coagulation cascade?

It activates Factor 12 to initiate the intrinsic part

Kalikrein

Converts HMWK to Bradykinin

Function of Bradykinin

Increases vascular permeability, pain, vasodilation

Normal Adult Bone marrow

- 50% fat cells

- Myeloid:Erythroid ratio = 2:1 - 7:1

Reticulocytes have a bluish color due to...

RNA remnants

Myeloblasts differentiate into ...

Basophils/mast cells

Eosinophils

Neutrophils

Sources of Iron

Heme = meat (more readily absorbed)

Non-Heme (veggies)

Steps of Iron Absorption

1. Iron binds to brush border and enters enterocyte

2. Iron leaves enterocyte via Ferroportin and enters blood stream

3. Binds to transferrin once in blood

(if iron need is low, it binds to ferritin and is stored intracellularly)

Iron absorption

a. Location of intestine

b. Requires what state of iron

a. Duodenum

b. Fe+2 state (more readily absorbed than Fe+3)

Why is iron always bound to transferrin in blood?

Can form free radicals if not bound

Ferroportin

Transport of iron into and out of cells

Hepcidin

Blocks ferroportin and lowers serum iron concentrations

(prevents duodenal enterocyte uptake of iron. also prevents recycling via macrophages)

When are levels of Hepcidin increased?

- when transferrin bound iron increases

- In iron overloading diseases

- In chronic inflammatory diseases

Transferrin

- Binds iron in blood and transports it to cells (liver and macrophages for storage)