What aspects should you figure out when taking a PATIENT HISTORY?

1. Primary complaints

2. Other diseases present

3. Past medical history

-History of diseases and injuries

4. Drug History

-Prescribed and recreational

5. Family History

-Inherited diseases

6. Social History

-Drugs, alcohol, lifestyle, environment, job...

Liquid=PLASMA (55-60% of blood)

Solid = CELLULAR (40-45% of blood)

-"Buffy Coat" (WBC's and platelets)

-Hematocrit (packed erythrocytes)

-RBC's

1060 kg/cubic meter

(Very similar to water, which is 1000 kg/cubic meter)

An aqueous solution of:

1. Electolytes (which maintain acid-base balance)

2. Proteins (7%)

3. Small organic molecules like glucose.

Main function is to transport O2  to tissues and to carry CO2 away from these tissues.

-Hemoglobin creates red color in this cell.

-The purpose of hemoglobin is to transport O2 to tissues.

1. Granulocytes

2. Lymphocytes (T cells and B cells)

3. Monocytes (Phagocytes)

Granulocytes are composed of what 3 types of cells?

-What are their primary functions?

1. Neutrophils (MOST COMMON. Are the first line of defense in inflammatory responses)

2. Eosinophils (used to attack parasitic worms)

3. Basophils (contain granules with amines like histimine. Have role in in allergies.)

Lymphocytes are composed what what types of cells?

-What types of immunity are they associated with?

1. T-Cells

-responsible for cell-mediated immunity. they

come from the thymus.

2. B-cells

-responsible for humoral immunity. They originate in the Bone marrow (Bursa of Fabricus)

-Are Monocytes RBC's or WBC's?

-What is their function/purpose?

-They are WBC's

-They exit into tissues to become MACROPHAGES

-they REMOVE DEBRIS,

-aid in INFLAMMATORY RESPONSE, 

-Process aged RBCs

-Help to present antigens to T-cells

Why are platelets important?

-Where are they produced?

1. Important in hemostasis (stopping blood flow) and blood circulation

2. Produced in the megakaryocytes in BM

1. Respiratory gas transport (O2 and CO2)

2. Transport of nutrients and waste products

3. Thermoregulation

4. Hemostasis (stopping of blood flow)

Hematopoeisis

Where is blood formed in the fetus?

Where is blood formed in an adult?

-Hematopoeisis first occurs in YOLK SAC MESODERM

-It then occurs in the fetal LIVER and SPLEEN

-Finally, hematopoeisis occurs in BONE MARROW

In adults, most blood is made in the axial skeleton and long bones

Aspiration: a needle is inserted into the marrow and a liquid sample is sucked into a syringe.

Biopsy: a solid core of bone marrow is examined as a histological specimen.

-Biopsy can contain fatty parts

What is a stem cell?

-Where is it located?

Undifferentiated cell that can divide continuously.

-Its daughter cells from specific irreversibly differentiated cell types

-It is located in the BONE MARROW

(*Pleuripotent Stem Cells are "founder cells")

Pleuripotential--> ________-> unipotential-->

-what is this cell type called?

-What are its two branches?

Multipotential stem cell

-It can become either a myeloid cell or a lymphoid cell.

a) As blood cells mature, their potentiality (increases/decreases)

b) As blood cells develop, mitotic activity
(increases/decreases)

a) Potentiality decreases.

-Mature cells have no potential. Once it is a certain type of cell, it usually stays that way.

b) mitotic activity increases.

at the end of progenitor cells and at the beginning of precursor cells

Order of cell types:

Stem cell-> Progenitor --> Precursor (BLASTS)--> Mature cells

-Stem cells are like "seeds", capable of self renewal

-What type of cells are the "soil"?

-What type of cells are the "fertilizer" (mediating action via receptors on target cells)?

"soil" = STROMAL cells

-(Fat cells, macrophages, endothelial cells, fibroblasts)

"fertilizer" = GROWTH FACTORS (Cytokines, growth factors, interferons)

Non-Lineage Specific: (act on pleuripotent stem cells to initiate self-renewal and differentiation)
a) IL-3

b) GM-CSF

Lineage Specific: (act on committed progenitor cells, involved in differentiation and maturation of blood cells)

a) G-CSF (Granulocyte colony stimulating factor)

b) M-CSF (Monocyte colony stimulating factor)

c) IL-5

d) EPO (erythropoeitin)

e) TPO (thrombopoeitin)

Erythrocytes:

a) Purpose

b) Lifespan

c) Morphology

-Purpose:Transport oxygen from lungs to tissues

-Lifespan: Live for approx 120 days

-Morphology: biconcave disk

-Have area of central pallor

Neutrophils:

a) Purpose

b) Lifespan

c) Morphology

a) Purpose: first line of defense against microorganisms

-quickly mobilized to the circulating blood

-Digests foreign organisms with phagocytosis. LYSOSOMAL ENZYMES in the presence of hydrogen peroxide, superoxide, and halides digest the ingested bacteria.

b) Lifespan: 1-2 days

c) Morphology: granulated, nucleated, 2-4 interconnected lobes.

Eosinophils:

a) Purpose

b) Lifespan

c) Morphology

a) Purpose: Defense against parasites

b) Lifespan: 

c) Morphology: 2 lobed nucleus. Contains large granules that stain red with eosin because of their basi

Basophils:

Morphology and purpose

Contain prominent blue-black granules that contain HISTIMINE

-Important in certain ALLERGIC REACTIONS

Monocytes:

-Morphology

-Purpose

-Have a kidney-bean shaped nucleus

-Phagocytic, but don't become mature MACROPHAGES until mature and enter tissues

-They remove old old RBCs

-Remove foreign cells

Lymphocytes:

a)Types and purpose

b) Morphology

a)

-B-cells (assicated with humoral immunity. become plasma cells which then produce immunoglobulin)

-T-cells (associated with cell-mediated immunity. Plays a role in elimination of foreign cells or viruses)

b) Morphology: Round nuclei, thin rim of cytoplasm. No granules.

Platelets:

a) Where do they mature from?

b) What is their major function?

c) How do they compare in size to a RBC?

a) mature from megakaryocytes

b) Major function is to preserve vascular integrity (and hemostasis)

c) They are smaller than RBCs

1. Hemoglobin (Hb) levels

2. Hematocrit (Hct) : volume of packed RBCs that occupies a volume of blood (%)

3. WBC count (differential includes % of each WBC type)

4. Platelet count (Plt)

5. RBC count

Also:

6. Mean Corpuscle Count (MCV): volume of average RBC

MCV = (Hct x 10)/ RBC count

7. Mean Corpuscular Hemoglobin (MCH): average amount of Hb in a single RBC

MCH = (Hb x 10)/ RBC count

8. Mean Corpuscular Hemoglobin Conc. (MCHC). Mean amount of Hb as % volume of RBC.

MCHC = MCH/MCV

IL-3

GM-CFU

EPO (says "I'm a red blood cell")

What is it called when cell loses nucleus and becomes RBC?

-How many divisions must a CFU-E undergo to become a mature RBC?

-What happens to the RNA as a RBC matures?

-Pyknotic

-Progeny of CFU-E stem cells enter a programmed sequence of 4 cell divisions

-As RBC matures, it loses its RNA

1. Anemia: too few RBCs

2. Polycythemia (erythrocytosis): too many RBCs

What are clinical symptoms of anemia?

What happens as a result?

1. Decreased RBC count

2. Decreased Hb

3. Decreased Hct

Result: Not enough oxygen carried to tissue...leads to HYPOXIA.

1. Genetic

2. Environmental (i.e. lack of essential nutrients)

3. Pathological (i.e. malaria)

4. Latrogenic (Side effect of particular treatment)

1. Microcytic anemia (smaller RBC than normal)

2. Normalcytic anemia (RBC is normal size)

3. Macrocytic anemia (larger RBC than normal)

When oxygen affinity INCREASES, which direction does the oxygen dissociation curve move?

-Examples

When oxygen affinity DECREASES, which direction does the oxygen dissociation curve move?

O2 affinity INCREASE-> curve shifts to LEFT.

-Example: H+ concentration in blood is reduced or when HbF is increased.

O2 affinity DECREASE-> curve shifts to RIGHT.

-Example: High altitude, Sickle Cell anemia

 What is the benefit of RBC's biconcave shape?

Increased surface area

a) What are the main oxygen carrying molecules in the body? How much oxygen to they bind? Which one is more regulated?

Hemoglobin (Hb) and Myoglobin (Mb). 

-Myglobin can bind 1 oxygen

-Hemoglobin can bind 4 oxygens

*Hemoglobin is highly regulated...myoglobin is NOT.
*Oxygen affinity for hemoglobin is ALWAYS lower oxygen affinity than myoglobin. This is because hemoglobin is always needing to release oxygen to tissues.

-The higher the pH (lower H+ concentration), higher the affinity for oxygen. Thus curve shifts to the left.

-The higher the amount of 2,3 DPG, oxygen affinity decreases, thus driving the curve to the right.

***NOTE: pH and 2,3 DPG has NO EFFECT on hemoglobin

-Allosteric affector for Hb is 2,3 DPG

-2,3 DPG shifts curve to the RIGHT, thus decreases oxygen affinity (causes oxygen to be released).

-2,3 DPG raises the P50 for binding of O2, thus decreasing affinity...pushing curve to RIGHT.

Where does 2,3 DPG bind on the hemoglobin?

What does this do to the hemoglobin?

a) 2,3 DPG binds to the CENTRAL cavity of hemoglobin.

b) 2,3 DPG gives hemoglobin its DEOXY form

-O2 does the exact opposite

1. Hyperventilation

2. Increased production of RBCs (to carry more O2)

3. Increased synthesis of 2,3 DPG (decreases oxygen affinity and shifts curve to the right).

1. HbF has 2 gamma chains.

-(HbA has 2 beta chains)

2. HbF has a HIGHER OXYGEN AFFINITY than HbA

3. HbF is not as positively charged, thus it can't bind the negatively charged 2,3 DPG as easily

How do competitors for the iron site affect hemoglobin?

-What kind of hemoglobin is this?

-Competitors such as CN-, SO, NO2, H2S... keep oxygen from being bound.

-This is called METHEMOGLOBIN and cannot bind oxygen.

Carbon dioxide (CO2) DECREASES oxygen affinity

-This happens by lowering the pH

-This, in times of increased activity, the body releases O2 more readily.

-Lungs have low CO2, so oxygen is readily bound. Rest of body produces lots of CO2, so oxygen is released.

The Bohr Effect: Linkage between H+, CO2, and O2

Porphyrins

Heme gives RBC its red color. It is called the "prosthetic group". A protein without its prosthetic group is called an "apoprotein".
-Heme is the most important part of hemoglobin because it allows for the binding of oxygen.

Cobalmin is another name for vitamin B12 (PINK)

What types of globin chains are in HbA2?

What types of globin chains are in HbF?

What types of globin chains are in HbA?

HbA2: 2 alpha chains and 2 delta chains

HbF:   2 alpha chains and 2 gamma chains

HbA:   2 alpha chains and 2 beta chains

1. Operational Iron (69%)

-Iron attached to Hb and Mb

2. Storage Iron (30%)

-Found in the liver, macrophages in BM, and spleen.

3. Labile iron (~1%)

-leftovers

4. Transport iron (<1%)

1. Reuse erythrocyte iron

2. Minimize blood loss

3. Uptake adequate amounts in diet

-Transferrin (carried by iron) bind to receptor and enters cell

-Heme is then synthesized

-Robosomes produce globin chains

-The heme and the globin chains join to produce hemoglobin.

List the stages of Iron Deficiency

(leading up to Anemia)

1. Iron Depletion

-Iron STORAGE DECREASED, but still have normal Hb and Hct levels.

2 & 3. Iron Deficiency (with or without anemia)

-ABSENT IRON STORES. Low serum iron, low transferrin, low Hb.

4. Severe (Advanced) Iron Deficient Anemia:

-Hypochromic-microcytic RBCs. 

-Decreased Ferritin

-Increased in transferrin saturation, increased reticulocyte (immature blood cell) count.

a) Blood Loss

-Gastrointestinal (hookworms, ulcers, etc) -Cancer

-Menstrual bleeding

-Blood donation

b) Runner's anemia

c) Lack of adequate intake (for babies, especially)

What are some symptoms of Iron Deficiency Anemia? Clinical signs?

-What kind of people are mostly affected?

Symptoms:
1. Decreased work tolerance

2. Shortness of breath, palpitations

3. Pallor in skin (Paleness)

Clinical Signs of Iron Deficiency:

1. Brittle nails

2. Sores on mouth

3. Tender tongue

4. Pica

5. Thrombocytosis (elevated platelets)

*People most affected are very young, on poor diets, or women

What is the treatment for Iron-Deficiency Anemia?

1. Find cause of iron imbalance

2. Take oral iron tablets (or IV iron, however this can be dangerous).

Cytokines pull iron out of the bloodstream by increasing levels of hepcidin. 

***This is probably not important for exam***

1. Huge RBCs (thus elevated MCV)

2. Hypersegmented NEUTROPHILS (MANY LOBES in nucleus)

3. RBCs have lost some pallor

4. BEEFY RED SMOOTH TONGUE

5. Neurological dysfunctions (due to B12 deficiency)

It is a MACROCYTIC anemia.

In megaloblastic anemia, what happens to DNA synthesis?

-RNA synthesis?

-Reticulocyte count?

-Slowed (retarded) DNA synthesis

-RNA synthesis stays the same

-Reticulocyte count is reduced (Due to BONE MARROW DEPRESSION).

-Abnormal shapes and sizes

-Mean cell volume  (MCV) is larger

-NORMAL amount of hemoglobin (MCHC)

-Decreased reticulocytes

-Shorter life span due to random destruction

a) Folate Deficiency (used in DNA synthesis)

-Inadequate intake

-Increased requirements (pregancy, etc)

-Blocked activation (Drugs, vit C deficiency...)

b) B12 deficiency

-Inadequate intake

-Inadequate absorption

-Competition for B12 (tapeworm, bacteria)

-Non functional TCII (responsible for binding B12 and transporting where it needs to go)

a) Can the body make folate?

b) Where can you get B12?

a) No. The body does not make folate...OR vitamin B12.

b) B12 comes from meat, milk, etc

-B12 becomes methylated into Methyl-B12

- Methyl-B12 then converts homocysteine into METHIONINE (necessary for DNA synthesis)
-Must have folate for this too

-B12 is also necessary for MYELIN SHEETHS

a) How long does it take to develop B12 deficiency?

b) How long does it take to develop folate deficiency?

a) B12 deficiency takes 8-10 years to develop

b) Folate deficiency develops in a matter of months

-Hemolytic Anemia may be HEREDITARY or ACQUIRED

-Causes may be due to:

1. Defects in the red cell membrane

2. Defects in red cell metabolism

3. The presense of abnormal hemoglobins

1. Innapropriate activation of the immune system

2. Ingestions of drugs and chemicals (interferes with the structure and function of RBC

3. Physical factors

4. Infectious diseases

5. Secondary effect of certain clinical conditions

1. JAUNDICE

2. Dark (tea colored or red) urine (HEMATURIA)

3. Increased pigmented gallstones

4. Chronic ankle ulcers

5. Splenomegaly

6. Increased folate requirement

1. Lots of bilirubin in blood

2. Increased erythropoeisis

3. Damaged/abnormally shaped RBCs

4. Intravascular hemolysis (Red blood cells are destroyed).

What are the two types of HEREDITARY hemolytic Anemias?

-What type of genetic inheritence?

1. Hereditary Spherocytic Anemia (HSA)

-AUTOSOMAL DOMINANT

2. G6PD Deficiency

-on X chromosome (affects males more)

Hereditary Spherocytic Anemia:
a) Physiology

b) Genetics

c) Treatment

a) Genes affect SPECTRIN

-Cells lose bits of their cell membrane eachtime they pass through the spleen. 

-RBCs slowly become spherical

-Spleen is working overtime to remove dying cells (splenomegaly).

b) AUTOSOMAL DOMINANT

c) Splenomegaly

***WILL RESULT IN

HOWELL-JOLLY BODIES: small blue DNA remnants in periphery of RBCs.

G6PD Deficiency:

a) Physiology

b) Genetics

c) Treatment

a) G6PD is a "housekeeping gene" which protects the RBC from oxidant stress.Under OXIDATIVE CRISIS, hemolytic anemia appears.

-During crisis, damaged/fragmented cells called "bite cells" may be present.

b) Mutant protein is A-

c) TREATMENT: Stop the offending drug/infection causing the crisis.

What are the two types of ACQUIRED Hemolytic Anemia?

-What is the pathophysiology?

-What antibody are they associated with?

1. Warm

-Production of autoantibodies of the igG antigens against antigens PRESENT ON RED BLOOD CELL MEMBRANES.

-Will show positive Coomb's test (clumping)

Treatment: IMMUNE SUPPRESSION, splenectomy, supplement with folic acid.

1. Cold

-Pathogenic antibodies are on igM, which bind to RBC's in COOLER extremities.

TEST with Coombs test at 37 degrees. If negative, do at 4 degrees.

-TREATMENT IS TO KEEP PATIENTS WARM

1. Alpha thalassemia

2. Beta thalassemia (corresponds to beta chains)

-Hypochromic-microcytic RBCs

-Increased reticulocyte count (inneffective erythropoeisis)

-Overproduced globin chains begin binding to themselves

MAIN POINT:

Alpha thalassemias are due to what genetic mutation?

How about Beta thalassemias?

Alpha thalassemia = DELETIONS

Beta Thalassemia = POINT MUTATIONS

1. What is the mode of inheritance of Beta Thalassemia?

2. In beta thalassemia, there is an overabundance of what kind of globin chains?

1. Beta Thalassemia is AUTOSOMAL RECESSIVE

2. There is an overabundance of ALPHA globin chains.

1. Major (Homozygous for B-thalassemia)

-NO HbA produced

-No B-chains produced

2. Intermedia

-Some B-chains produced

-Varying levels of HbA

3. Minor (Heterozygous for B-thalassemia)

-Lots of HbA

-considerable amounts of B-chains

a-thalassemia and B-thalassemia

a-globins normally have 4 genes expressed. Deletions of these genes can lead to a-thalassemia due to UNEQUAL CROSSING OVER (recombination).

1 deletion = SILENT CARRIER

2 Deletion = a-thalassemia TRAIT

3 deletions = HbH disease

4 deletions = hydrops fetalis (infant death)

a) Bart's Hb is in fetal blood (excess gamma chains)

-HAVE MUCH HIGHER OXYGEN AFFINITY!!!!!

b) HbH is a-thalassemia proper. There is an overproduction of B-globin

-Produces HEINZ BODIES

If major:

-Blood transfusions

-Avoid high iron foods

If minor (trait):

-Folate suppliments

In thalassemia, IRON OVERLOAD= BAD (need chelation therapy)

In HbS, glutamic aid has been replaced by VALINE at the 6th amino acid from the N-terminus of Beta chain.

-This causes SICKLING

How is malaria diagnosed?

How is it treated?

It is diagnosed using a Giemsa stain.

-It is treated with antibiotics, Malarone, or Mefloquine

In deoxygenated environments, Deoxy HbS polymerizes thus leading to sickling of cells. 

-This happens because the Valines in deoxygenated HbS are exposed and stick together to avoid water (Hydrophobic).

-As the RBCs sickle, they can obstruct capillary flow. This leads to further hypoxia, which leads to MORE sickling.

What are some crisis in Sickle Cell anemia?

What is Treatment of Sickle Cell Anemia?

1. Vaso-occlusive infarcts (dead spots), etc.

2. Treatment is to prevent crisis. Homozygous HbS patients need folic acid supplements.

-Stimulation of HbF can inhibit HbS polymerization. (using HYDROXYUREA as drug of choice )

- Gene therapy will eventually be another way to treat sickle cell anemia.

1. Neutrophil: Multilobed nucleus

2. Monocyte: Large cell, large central nucleus

3. Eosinophils: bilobed nucleus

4. Basophils: Many dark staining granules

What is a BAND CELL?

What is a PMN?

-It is a precursor for production of neutrophils. It has a kidney shaped nucleus

-PMN is a mature nucleophil

What are the two types of inflammation?

How do they differ? (time, type of immunity, dominating cell type, duration, vascular response)

Two types of inflammation are ACUTE and CHRONIC.

1. Acute

-Immediate reaction and fast onset

-Associated with INNATE immunity

-NEUTROPHIL cell dominance

-Last for hours to weeks

-High vascular response

2. Chronic

-Persistent reaction and slow response

-Cell-mediated immunity

-Mononuclear cell dominance (lymphocytes, monocytes, platelets)

-Duration weeks to years

-Less prominent vascular response

1. Redness (rubor)

2. Heat (calore)

3. Swelling (tumor)

4. Pain (dolore)

a) What is EDEMA?

b) What is Exudate?

c) What is Transudate?

a) Edema: accumulation of fluid within an extravascular compartment (outside swelling)

b) Exudate: fluid rich in protein and cellular elements that oozes out of blood vessels due to inflammation.

c) Transudate: filtrate of blood from the blood serum

Neutrophil undergoes TRANSMIGRATION. It squeezes out of the blood vessel and into tissue.

-WBCs flow towards chemical mediators (granules released by other WBCs)

What are the two main types of immunity?

Briefly describe them.

INNATE and ACQUIRED (each one has humoral and cell mediated)

Innate:is present at birth. Not specific.

- enzymes, mucous, urination, defication, etc.

-PHAGOCYTIC CELLS (neutrophils)

ACQUIRED is antigen specific. Requires prior exposure.

1. Neutrophils. Have short lifespan

2. Monocytes. Longer lifespan. (present antigens to T-cells)

3. Macrophages (mature monocytes). Longer lifespan

****Phagocytic cells have lysozymes that break down bacteria

How is Fatal Pneumonia caused?

1. Anaphylatoxins are released and increase the vascular permeability.

2. -Chemoattractants bring white blood cells to site of injury

3. Complement protein C3 tags invading bacteria.

What are the 3 ways that C3 can be activated?

What is the significance of C3?

1. Classical (antibody/antigen complex)

2. Lectin binding

3. Alternative

(OPSONIZATION by C3****)

When C3 tag is combined with Antibody tag, both cells are destroyed.

-Makes chemotaxis molecules

-Stimulates MAST CELLS (which then release histimine)

1. Plasma cell

2. Memory cell

Macrophages have Nitric Oxide, have multiple functions, and live longer than Neutrophils (T/F)

What are the causes of Chronic Inflammation?

-What are end results of Chronic inflammation?

1. Follows acute inflammation

2. May begin slowly

3. Exposure to potentially toxic substances

END RESULTS: Lots of scarring (fibroblasts)!

What is a Plasma Cell?

What is a memory cell?

-B-cell that produces specific antibody

-B cell that reverts to dormant state but is reactivated when antigen is presented again.

Helper T cells have what CD#?

When activated, what do they do?

CD4+

-When activated, they release cytokines which help activate B-cells!

Th1 cells stimulate------

Th2 cells stimulate ----------

T helper cells can also activate ------

Th1 cells stimulate macrophages

Th2 cells stimulate B-cells

T helper cells can also activate Killer T-cells

1. T helper cells (CD4)

CD8+

2. Ts (regulatory/suppressor T cells)

3. Cytoxic T-cells 

4. Memory T-cells

1. Blood filtration

2. Blood pooling

3. Immune function

4. Hematopoeitic function

Red Pulp: Cords and sinuses

White Pulp: B and T lymphocytes

Marginal Zone: Antigen presenting cells

a)What is Granulomatous Inflammation?

b) how does the body deal with it?

a) Neutrophils can't digest foreign substances.

THUS, neutrophils die and foreign substance is still present.

-The cycle repeats...over and over and over

b) The body deals with it by using macrophages instead. Macrophages can LIVE LONGER.

-They then become an epithelioid cell and produce factors that aid in the immune response.

a) What is Chronic Granulamatous Disease?

b) How is it treated?

a) body cannot produce BACTERICIDAL SUPEROXIDE (can't do oxidative burst)

-As a result, granulomas develop

-Thus, people are susceptable to catalase positive microorganisms (i.e. staph aureus).

-Catalase negative organisms, however, kill themselves by producing their own H202.

b)

TB (Tuberculosis) is caused by a bacterium. How is it spread? How is it treated?

Why is it bad with HIV?

It is spread through respiratory system. Can cause necrosis in the lungs.

-It is treated with antibiotics, but the disease is highly drug resistent

***If a person has HIV, the TB is worsened (and vice versa)***

Too many white blood cells! (this is a benign disease

In NEUTROPHILIA, ther are the presence of Doehle bodies!

What virus causes mononucleosis?

Pathophysiology?

Treatment?

Epstein-Barr Virus

-Infects B-cells

TREATMENT=REST REST REST

Define: (are they pathological?)

1. Hyperplasia

2. Hypertrophy

3. Metaplasia

4. Dysplasia

5. Neoplasia

1. Hyperplasia: increase in cell size (can be normal)

2. Hypertrophy: increase in tissue mass (can be normal)

-When be pathological when unregulated.

3. Metaplasia: replacement of one cell type for another.

- e.g. stomach cells in esophagus

-Usually reversable

4. Dysplasia: Atypical proliferation of cells

-Abnormal appearance

-Disorderly arrangement

-MAY BE PRECURSOR TO CANCER!

5. Neoplasia: Abnormal growth/ excessive growth.

-NOT RESPONSIVE to stimulus removal.

-Thus, there is no regulation of growth control genes.

-Can be BENIGN or

MALIGNANT (spreading to other tissues).

Leukemia and Lymphomas: Unregulated clonal proliferation of hematopoetic stem cells.

1. Acute

-Lympoid (ALL)

-Myeloid (AML)

2. Chronic

-Lymphoid (CLL)

-Myeloid (CML)

Acute Myeloid Leukemia (AML) is...

Acute Lymphoblastic Leukemia (ALL)...

a) affects who?

Months to years (rather than weeks to months in Acute Leukemias)

-MORE DIFFICULT TO TREAT!

Hodgkins 

Non-Hodgkins

What are the common age groups for the following diseases?
ALL

AML

CML

CLL

ALL = Mostly children

AML = Incidence rises with age

CML = Incidence rises with age

CLL = Mostly old age

1. Oncogenes

2. Tumor suppressors

3. Chromosomal aberrations

1. If right in between a tumor suppressor

2. Could get two copies of an oncogene

3. Translocation of protooncogene onto unregulated promoter.

1. Karyotype: Direct analysis of chromosomes from tumor cells.

2. Flourescent in situ hybridization (FISH): Flourescently labeled probes are useful in finding translocations and gene duplications

3. Microarray analysis: analysis of transcription in tumor cells (useful in diagnosing different types of leukemia)

4. Restriction Fragment Length Polymorphism (RFLP) 

-Used in paternity testing

-Usefuly in finding particular gene sequences of interest.

CML exhibits thromocytosis

AML exhibits thrombocytopenia

1. Chronic phase (asymptomatic)

2. Accelerated phase (increased myeloblasts,etc)

3. Blast Crisis (behaves like an acute leukemia)

-LOTS of BLASTS

Fusion of BCR-ABL causes what disease?

-What does it do?

- causes CML

-It enhances proliferation (turns off differentiation)

Chromosomes 9 and 22

-Addition to 9

-Loss from 22

1. Bone Marrow Transplant (but very dangerous)

2. Gleevec (inhibits BCR-ABL kinase)

-However, drug resistence has developed

-overexpression of BCR-ABL make it hard to control. Mutations have occured in kinase domain.

What type of B cells are found in Chronic Lymphoid Leukemia (CLL)?

-What is CLL?

CD5+ B-cells

-Malignancy of B-cells

What is the gene expressed in CLL?

-What does it do?

-What is the favorable prognosis?

Gene expressed is Bcl-2

-This gene inhibits apoptosis

del13q14 is the favorable prognosis

How is CLL different from CML?

How does a person usually die from CLL?

CLL exhibits FREQUENT INFECTIONS!

-Patient usually dies from bone marrow failure.

There is no cure. Mostly just improve qualitiy of life.

-Richter's Transformation?

-Monoclonal Antibody Therapy:

Rifluxan (antibody to CD20)

Alemtuzumab (antibody to CD52)

Clumps of granular material that form elongated needles.

-Associated with AML

-Cytoxic chemotherapy

-Bone Marrow Transplants

Rapid onset...malignancy of commited LYMPHOID CELLS.

-High Nucleus to Cell ratio 

1. Precursor B-cell:

postive for CD10, CD19, CD34

2. Mature B-cell:

positive for CD10, CD19, CD20, CD22

-negative for CD34

3. Precursor T-cell:

-positive for CD3,CD4, CD8

1. Remission reduction (destroy as many cells as possible with chemotherapy)

2. CNS prphylaxis

3. Maintenance in remission