What percentage of your blood is cellular?

Related to cellular, what is the composition of the cellular portion?

What percent of blood is fluid? What does that component consist of?

What percentage of your blood is cellular? 40-48%

Related to cellular, what is the composition of the cellular portion? RBC, WBC, Platelets

What percent of blood is fluid? 52-60%

What does that component consist of? Plasma and serum

transport

defense

Regulation of body temperature

Hemostasis

What are the stimulators that promote hematopoiesis?

What is the name of the cell that responds to perceived metabolic needs in commitment to specific cell line production?

What are the stimulators that promote hematopoiesis?

Erythropoietin

Leukopoetin

Thrombopoetin

cytokines

interleukins

What is the name of the cell that responds to perceived metabolic needs in commitment to specific cell line production?

PURIPOTENTIAL STEM CELL

What are sites of erythropoiesis in an adult vs a fetus?

Adult (4)

Fetus (5)

Sites—Adult

Bone marrow of axial skeleton, proximal epiphyses of long bones, skull; lymph nodes

Sites—Fetus

Yolk sac, placenta→bone marrow, spleen, liver, lymph nodes

What type of cell is released to replace senescent RBCs?

Are they slightly larger or smaller than mature RBCs?

How would you describe the MCHC of this type of cell?

What type of cell is released to replace senescent RBCs? RETICULOCYTES ("adolescent")

Are they slightly larger or smaller than mature RBCs?

 slightly larger

How would you describe the MCHC of this type of cell?

polychromatophilic

biconcave disc

Reversible deformability

What is a senescent erythrocyte?

Who helps to remove it from circulation?

What protein helps to recycle it?

It's part of what type of production?

What is a senescent erythrocyte? aged, damaged, abnormal RBC's removed from circulation

Who helps to remove it from circulation?

 Macrophages of spleen, liver, BM

What protein helps to recycle it? transferrin; iron (stored in tissues as ferritin), globin

It's part of what type of production? bilirubin production

Hgb A, 2 alpha, 2 beta

Hgb A2, 2 alpha 2 delta

Hgb F (predom Hgb in fetus), 2 alpha, 2 gamma

HgbS: 2 alpha, 2 beta (substitution of valine for glutamic acid)

What does hematocrit measure?

What does hemoglobin measure?

Hematocrit: mesure of packed red cell volume

Hgb: measure of total amt hgb in blood

What is the composition of a RBC?

Globin molecule: 2 pairs of amino acid chains

type of Hgb based on AA pairs

4 heme units: contain iron

What are the RBC indices?

What do they measure?

MCV: avg volume (size) of single RBC

MCH: avg RBC mass

MCHC: concentration of hgb in single RBC

What are type sof blood abnormalities?

(3)

hemochromatosis (overload of iron)

cab be primary (genetic)

secondary (ie. alcoholism)

Polycythemia

Primary

Secondary: ie. COPD

Anemia

decreased RBC or Hgb OR BOTH

categorize based on RBC indices

Impaired O2 transport and recruitment of compensatory mechanisms

Alterations in Hgb levels and red cell number and appearance

Signs and sxs assoc with the pathologic process that is causing the anemia

How would you describe morphology changes in RBC?

(2)

Anisocytosis: size

poikilocytosis: shape

ANEMIA:

What are pathologies causing impaired production?

What are pathologies leading to excessive loss/increased destruction?

What are pathologies causing impaired production?

lack building blocks, stimulators

abnormal genetic code

What are pathologies leading to excessive loss/increased destruction?

Abnormal genetic code

Intravascular

Extravascular

• AIDS
• osteomyelitis
• chronic renal failure
• RA
• sequestering iron in the psleen and contribute to RBC destruction
• lymphocytes release cytokines that suppress erythropoietin production and action

What are causes of hemolytic anemia?

(4)

Intravascular hemolysis: may be due to transfusion reaction, mechanical injury, toxins

Extravascular hemolysis: when abnormal RBCs are phagocytized in the spoleen as in sick cell anemia

Intrinsic causes may be due to defects in RBC mebranes, hemoglobinapathies, inherited defects

Extrinsic or acquired causs may be due to drugs, bacterial toxins, antibodies, physical trauma

Name the disease causing excessive loss/increased destruction:

1. autosomal dominant disorder affecting RBC membrane proteins

2. absent or defective synthesis of alpha or the beta hgb chains)

3. Hgb gets denatured

4. abnormal substitution of a single AA valine for glutamic acid

1. autosomal dominant disorder affecting RBC membrane proteins HEREDITARY SPHEROCYTOSIS

2. absent or defective synthesis of alpha or the beta hgb chains) THALASSEMIA

3. Hgb gets denatured G6PD DEFICIENCY- seen in AA population

4. abnormal substitution of a single AA valine for glutamic acid: SICKLE CELL DISEASE

Pt presents saying they feel fature, weakness, dyspnea, palpitations, angina, headache, fainting, visual changes, pallor tachycardia, heart murmur, splenomegaly, jaundice....

What are you thinking?

Name the disease:

A proliferative disease of the bone marrow with an absolute increase in total RBC mass with elevated white cell and platelet counts

if you noticed the following:

hematocrit >54% in male

Hematocrit > 51% in female

abnormally high total RBC mass

What are you thinking?

Name the disease.

It is caused by alloantibodies.

Comes from an exogenous source

An antibody produced by a person to an antigen within the same species but that is not present in that person.

GRANULOCYTES

Neutrophils

Eosinophils

Basophils

AGRANULOCYTES

lymphocytes (lymphoid cell line)

monocytes (myeloid cell line)

Neutrophils

Function:maintain normal host defenses

Life Span: 4-5 days

Normal Percentage: 55-65%

Eosinophils

Function:detoxify agents assoc with allergic reactions

Life Span: not known

Normal Percentage:1-3%

Basophils

Function:role in allergic reactions

Life Span:unknown

Normal Percentage: 0.3-0.5%

Lymphocytes

Function:B-cells differential to form antibody-producing plasma cells, involved in humoral-mediated immunity

T-cells responsibel for orchestrating the immune response and effecting cell-mediated immunity

Life Span:hours to years

Normal Percentage: 20-30%

**maturation sequence: T cells, B cells

Function: phagocytes

Life span: 1-3 days in the circulation; months to years in tissues

Normal percentages: 3-8%

If a pt had chronic infections such as TB, syphillis and leukemia.

What would you expect to see in WBC counts?

If you had a patient who had

an invasive parasitic disease

allergic reaction

Hodgkins disease

Leukemia

What would you expect to see on their WBC count?

A patient with a viral illness or HIV.

What would you abnormality would you expect to see in their WBC count?

What abnormality would you expect to see on pt's WBC count if they had

drug-induced illness cuasing defective production of a certain WBC and an immune destruction?

If a patient had chronic myelogenous leukemia,

what type of WBC would you expect to see increased?

basophils

therefore...basophilia

Name the disorder:

Referring to a group of disorders characterized by autonomous proliferation of one or more hematopoietic elements in the bone marrow. In many cases, th eliver and spleen are enlarged.

Name the disorder.

Plasma cell cancer of the osseous tissue; in the course of its dissemination, may also involve non-osseous sites; characterized by uncontrolled proliferation of an abnormal clone of plasma cells, which secrete primarily IgG or IgA.

Acute lymphocytic

Chronic lymphocytic

Acute myelogenous (granulocytes, monocytes)

Chronic myelogenous

Name the disease.

Malignant neoplasms coming from the transformation of a single cell line orginally derived from hematopoetic stem cells.

Hodgkin's disease

Non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma

viral cause is suspected

can orginate in T cells or B cells

Inflammation involves ______ and _______components.

Unlike immune response, there is no _____

Involves ___, ___, ____

Inflammation involves vascular and cellular components.

Unlike immune response, there is no memory.

Involves blood vessels, chemical mediators WBC's

1. Limit and control injury (inflammation)

2. Prevent further tissue damage.

3. Prepare area of healing.

4. Remove bacteria and dead cells

What are the five cardinal signs of inflammation?

R, S, H, P, L

REDNESS

SWELLING

HEAT OR TEMPERATURE

PAIN

LOSS OF FUNCTION

Initial vasoconstriction at injury site.

Vasodilation of capillaries-slows and increases blood flow to the area. Increases hydrostatic pressure.

capillary permeability increases- leakage of plasma proteins (exudate) causes edema

Tissue oncotic pressure increases

Increased blood flow causes increased warmth and redness

Constriction of blood vessels followed by vasodilation of arterioles/venules causes congestion, REDNESS, WARMTH

Blood vessels become smore permeable, proteins exit, fluid moves into tissues so you get SWELLING, PAIN and LOSS OF FUNCTION

this helps keep infection localized

Minor injury: immed transient response

Moderate injury: immed sustained response lasts for several days, vessel damage in the area

Delayed response- occurs 4-24 hours later, injury is not noticed right away (sunburn)

Explain the cellular phase of acute inflammation.

1. Neutrophils and monocytes move into the area

2. Margination and adhesion: phagocytes adhere to the blood vessel walls

3. Emigration (diapedesis)

Phagocytes slip though blood vessel walls via endothelial junctions

4. Chemotaxis: chemical "perfume" helps attract the leukocytes to the area

5. Phagocytosis

Adherence plus opsonization then ENGULFMENT (intracellular destroying)

What is the name of the receptor that is on the surface of cells and their function is to respond to early tissue injury?

It is thought that genetic differences in these receptors is what causes some people to be more susceptible to infections.

What is the receptor? Name examples of cells that bind to the recetors.

What is the name of the receptor that is on the surface of cells and their function is to respond to early tissue injury? TOLL LIKE RECEPTOR

Name examples of cells that bind to the recetors.

mucosal epthelial cells, mast cells, dendritic cells in skin, neutrophils, macrophages

What type of cells can divide and survive at inflammation sites?

Which cells CANNOT?

What type of cells can divide and survive at inflammation sites? macrophages

Which cells CANNOT? neutrophils

What factors are secreted by the macrophages that help activate other inflammatory cells?

granulocyte colonystimulating factor

Gamma interferon

Interleukin 1

Fibroblast activating factor

1. The Complement System

2. The Clotting System

3. The Kinin System

This system is potent against bacterial infections.

It can destroy pathogens DIRECTLY or assist in killing pathogens.

Opsonization, Degranulation and causes contraction of smooth muscle.

What's the system?

Classical pathway: proteisn of acquired immune system (antigen-antibody)

Lectin pathway- certain bacterial carbohydrates

Alternative pathway- gram neg bacteria and fungal cell wall components

The following are part of what system:

1. Opsonization

2. Mast Cell Degranulation

3. Leukocyte Chemotaxis

4. Cell Lysis- Enzymes

Clotting system

this plasma protein system works closely with coagulation system.

It works closely with ______.

At low doses it causes ____.

Acts with ___ to induce pain.

Causes smooth muscle cell contraction.

Increases vascular permeability and leukocyte chemotaxis.

KININ SYSTEM

It works closely with coagulation system.

At low doses it causes VASODILATION.

Acts with PROSTAGLANDINS to induce pain.

1. histamine/serotonin- causes vessel dilation

2. arachidonic acid metbolites- prostaglandins, leukotrienes, thromboxane A2 (vasoconstriction platelet clumping)

3. Platelet Activating factor- causes platelet aggregation

4. Cytokines

5. Nitric Oxide- smooth muscle relaxation; reduces platelet aggregation and adhesion, helps with phagocytosis

Natural killer cells: recognition and elimination of cells infected with viruses.

Platelets: activated several ways, stop bleeding, contain coagulation proteins (fibrinogen), adhesion molecules and growth factors

Name the cell described.

cellular bags of granules located in loose connective tissue, close to blood vessels and areas exposed to environment- skin, Gi, Resp.

Physical injury- heat, trauma, UV light, X-ray

Chemical agents- toxins, bsee stings, snake venom

Immunologic means- antibody-antigen complement

Activation of TLR's-bacteria and viruses

This chemical inflammatory mediator is produced by macrophages and monocytes.

It includes

Interleukin 6, 1 beta

Tumor necrosis factor- alpha

interferon gamma

Transforming growth factor TG-beta

CYTOKINES

Diffuse over ____ distances and bind to target cells.

Various activites dependining on target cell.

The majority of cytokines are ___ or ____.

Diffuse over SHORT distances and bind to target cells.

Various activites dependining on target cell.

The majority of cytokines are INTERLEUKINS or INTERFERONS.

Who produces interleukins?

Interferons protect against what type of infections?

Interleukins produced by macrophages

Interferons protect against viral infections

Who secretes TNF alpha?

Increases ___in the liver.

can cause __or ___ in prolonged infection.

Causes ___ of some tumors/ promotes ____ of some tumors.

Who secretes TNF alpha? macrophages

Increases pro-inflammatory proteins in the liver.

can cause cachexia or muscle wasting in prolonged infection.

Causes necrosis of some tumors/ promotes growth of some tumors.

What composes exudates? (2)

Name four different types.

Exudates: plasma protein and cell debris.

Serous: watery, low plasma proteins, early or mild inflammation

Fibrinous: more severe inflammation, lungs in pneumonia, thick, sticky fibers

Purulent: large number of leukocytes, bacterial infections, pus, tissues, proteins

Hemorrhagic- bleeding, filled with erythrocytes (blood blister) more severe tissue damage

Abscess: localixed area of inflmmation containing purulent exudate.

Ulcers: occur on epithelial tissues liek Gi tract or skin as a result of inflammation or vascular compromise

Fever, leukocytosis, increase in circulation of plasma proteins (acute phase reactants) and lympadentis.

THESE ARE ALL ____ SIGNS OF ______.

LOOK AT PAGE 498 in the book

read about fever patho

What system is involved in the following:

nonspecific response to mediators released rom injured tissue.

Immunologic response to a specific antigen.

at least 2 weeks

can lasts weeks, months or years

What can form in chronic inflammation?

What is it doing?

____ fuse to form multinucleated gian cells.

Surrounded by _____.

What can form in chronic inflammation? granulomas

What is it doing? wall off area

Macrophages fuse to form multinucleated giant cells.

Surrounded by lymphocytes.

What is Omega 3 found in?

What is Omega 6 found in?

Omega 3:green leafy veg, walnuts, flaxseed, fish oils

Omega 6: various veg oils

**Compete for an enzyme that helps produce anti-inflam PGs

What does wound healing begin with?

What is involved?

Phagocytosis of fibrin, dissolved clots, erythrocytes and dead tissue at the site.

Involves: fillin, seal, shrink the wound

1. Labile cells: continually divide- surface epithleium, uterine, vaginal tissue, Gi tract

2. Stable cells: stop dividing when growth stops but can regenerate (bone marrow, liver)

3. Permanent or fixed cells- don't undergo mitosis any more- nerve cells, cardiac muscle tissue, skeletal muscle cells once destroyed they're replaced with scar tissue

What does this refer to:

collagen that restores structural integrity of the area but does NOT restore physiologic function

SCAR TISSUE/FORMATIOn

In some cases, scarring can compromise function ie. heart

Reconstruction phase

Maturation Phase

What cell is involved in reconstruction phase? What is its function?

In ___ days, ____ and in large wounds ____ occurs.

What cell is involved in reconstruction phase? FIBROBLAST What is its function? synthesize and secrete collagen

In 2-3 days, EPITHELIALIZATION and in large wounds GRANULATION TISSUE occurs.

WOUND HEALING:

When does maturation occur? how long can it last?

What do you NEVER regain?

When does maturation occur? begins 3 weeks after injury

how long can it last? can last 6 mts or longer

What do you NEVER regain? orginial tissue

HOW THE WOUND HEALS:

What's the difference between primary and secondary intention?

Primary: minimal tissue loss, heals by opposition of wound edges (ie. surgical incision)

Secondary:edges of the wound are unable to be opposed; healing will occur with excess trauma or tearing of the skin-ie dog bite.

What is the outcome during healing if any of the following occurS:

• inflammatory response
• wound become reinfected
• pts with Dm, immunocompromised
• hypoxemia
• Certain drugs or lack of nutrients (increase need for protein)
• prolonged bleeding- delays healing
• fibrous adhesions form- binds organ together
• Prolonged infection: prolongs inflmmation, increases purulent exudate, excess scar formation
• hypovolema with excess bleeding- bessel constriciton
• NSAIDS, steroids

inhibits fibroblast migration to the wound

impairs angiogenesis, wound contraction and epithelialization

ERRORS IN RECONSTRUCTIOn:

Explain the following:

1. Keloids

2. Hypertrophic scar

3. Wound dehiscence

4. Contracture

1. Keloids: large raised scar extending beyond the margins of the orginal wound; improper collagen formation

2. Hypertrophic scar: raised by stays within boundaries of wound

3. Wound dehiscence: pulling apart at the edges, greates 5-12 days after suturing, often with wound sepsis/excessive strain/obesity may see serous drainage from wound; nees surgical repair

4. Contracture: deformity at the site of the wound; functio laesa (decrease ROM) burns, cirrhosis, duodenal strictures from ulcers healing

True or False

EVERY cell in the body contain the same genetic information.

What are the four bases making up the alphabet of the genetic code?

What creates a complimentary MRNA copy?

Adenosine

Cytosine

Guanine

Thymine

What creates a complimentary MRNA copy? Transcription

CELL DIVISION:

what are the terms that describes the following:

this cell division occurs in SOMATIC cells; results in the formation of 23 pairs of chromosomes

This cell division is limited to replicating germ cells

Resulst in teh formation of gametes or reproductive cells; each has a single set of 23 chromosomes

this cell division occurs in SOMATIC cells; results in the formation of 23 pairs of chromosomes MITOSIS

This cell division is limited to replicating germ cells

Resulst in teh formation of gametes or reproductive cells; each has a single set of 23 chromosomes MEIOSIS

Mitosis: one division 2 daughter cells; same number of chromosome cells in daughter and parent; somatic cells; throughout life used for growth and repair

MEIOSIS: 2 divisions; 4 daughter cells per cycle; daughter cells genetically different; half number of chromosomes in a daughter vs parent cells; germline cells; in humans, complete after sexual maturity; used for sexual reproduction, new gene combinations

Mitosis vs Meiosis:

What has cells that go to the offspring?

All males have an __ and ___ sex chromosome.

All females have two __ chromosomes

All males have an X and Y sex chromosome.

All females have two X chromosomes

There are __ pairs of chromosomes alike in males and females.

__ chromosomes make up the 23rd pair, determining sex of person.

There are 22 pairs of chromoses alike in males and females.

SEX chromosomes make up the 23rd pair, determining sex of person.

TRANSMISSION OF GENETIC INFORMATION

What is an allele?

What is a locus?

What is a chromosome?

What is an allele? alternate forms of a gene; one from each parent

What is a locus? position genes occupy on a chromosome/ location of allele

What is a chromosome? genes are organized in structures

The physical manifestation of genetic information. What is the term?

The sum total of genetic information in the cells. What is the term?

The physical manifestation of genetic information. What is the term? PHENOTYPE

The sum total of genetic information in the cells. What is the term? GENTOTYPE

substitution of one base pair for another

The loss or addition of one or more base pairs

The rearrangement of base pairs.

TRUE OR FALSE

Mutations in DNA ONLY occur in germ cells.

FALSE

Mutations may arise in somatic cells OR in germ cells.

What gene disorder is caused by a single defective or mutant gene?

It can be present on an autosome or the X chromosome.

It may affect one member or both members of an autosomal gene pair.

their patterns of transmission and can be obtained througha  family genetic history.

Defects follow the Mendelian pattern of inheritance

Arrangement of Alleles:

Define homozygotes.

Define heterozygotes.

Define homozygotes: persons in whome the two alleles of a given pair are the same

Define heterozygotes: persons having different alleles (Aa) at a gene locus

GENETIC TRAITS.

Define recessive trait.

Define dominant trait.

Define carrier.

Define recessive trait: one expressed only in a homozygous pairing.

Define dominant trait: one expressed in eith a homozygous or a heterozygous pairing

Define carrier: a person who is heterozygous for a recessive trait and does NOT manifest the trait.

DISORDERS OF SINGLE GENE INHERITANCE.

What does it mean to have an autosomal dominant mutation?

Autosomal recessive mutation?

X-linked recessive mutation?

What does it mean to have an autosomal dominant mutation? a single mutant allele from an affected parent is transmitted to an offspring regardless of sex

Autosomal recessive mutation? manifested only when both members of the gene pair are affected (both parents unaffected, but carriers)

X-linked recessive mutation? always associated with the X chromosome; inheritance pattern is predominantly recessive.

AUTOSOMAL DOMINANT SINGLE GENE DISEASES:

1. does it skip generations?

2. What is the recurrence risk?

3. When does it happen? at birth or later in life?

1. does it skip generations? not seen typically

2. What is the recurrence risk? 50%

3. When does it happen? at birth or later in life?

occurs later in life

Huntinton's Chorea: atrophy and loss of striatal neurons in the caudate nucleus, putamen and frontal cortex

assoc with triplet of CAg on short arm of chromosome 4

familial hypercholesterolema: mutation in the LDl receptor produce a deficit in receptor abundance, resultin gin increased circulating LDL levels

Marfan's syndrome: a connective tissue disorder manifested by changes in the skeleton, eyes, and cardiovascular system

due to mutation in gene that encodes in fibrillin, a key component of connective tissue

Von Willebrand's disease: platelet adhesion defect

Cystic Fibrosis: most common AR disease, mutation in gene result in absent or abnormal expression of the chloride channel as well as misregulation of a sodium channel

Sick Cell Disease: seen in 1/600 AA births. Caused by mutation in the beta globin gene on chromosome 11, alters the hemoglobin molecule, erythocytes assyme "sickle" shape under condition of low oxygen tension

X-Linked (X Chromosome) SINGLE GENE DISEASE:

ONLY on _ chromosomes

ONLY ___ are affected.

is it common to skip a generation?

___ can be carriers, and 50% of __ will have trait/disease.

ONLY on X chromosomes

ONLY MALES are affected.

is it common to skip a generation? YES!!!

FEMALES can be carriers, and 50% of SONS will have trait/disease.

Hemophilia A: Deficiency of clotting factor VIII, a protein that is encoded by a gene on the long arm of the X chromosome

Duchenne muscular dystrophy: mutation in gene that encodes dystrophin, vital muscle protein

Fragile X syndrome: Assoc with a fragile site on teh X chromosome where the chromatin fails to condense during mitosis

Second most common cause of mental retardation after Downs syndrome.

Name three causes of chromosomal disorders.

Name 3 examples.

Alterations in chromosome duplication.

Alteration in chromsome number

Trisomy 21

Monosomy X

Polosomy X

Alterations in chromosome structure

What happens during cell division in trisomy-21?

What are some signs and symptoms?

Non-dysjunction during meiosis

growth failure

metnal retardation

flat back of head

abnormal ears

pam crease

special skin w ridge pattern

umbilical hernia

diminished muscle tone

big toes widely space

enlarged colon

congenital heart disease

big wrinkled tongue

dental anomalies

broat flat face, slanting eyes, epicanthic eyefold, short nose

Small and arched palate

Name the chromosomal disorder.

99% are spontaneously aborted.

Absense of ovaries.

Most common genetic cause of amenorrhea

Webbing of neck.

Lymphedema of the hands and feet.

MONOSOMY X (23)

TURNER SYNDROME (45, X)

Name the chromosomal disorder:

Affects males.

due to NON-dysjunction during meiosis.

tall males, normal at brith

Seminiferous tubule dysgensis, gynecomastia.

NOT mentally retarded.

POLYSOMY X: XXY, XXXY

Klinefelter's syndrome (47, XXY)

What are environmental influences causing chromosomal disorders?

• Teratogenic agents: produce abnormalities during embryonic or fetal development:
• radiation
• Chemical and drugs: fetal alcohol syndrome, cocaine babies, folic acid deficiency
• Infectious agents ie. H. Pylori

Assessmetn of genetic risk and prognosis

Detailed FHx

Pregn Hx

Detailed accounts of birth process

Accoutn sof postnatal health and development

Physical exam of affected child and family

Lab tests

all the above are part of what assessment?

1. vessel spasm

2. formation of platelet plus

3. blood clot formation

4. clot retraction and fibrous tissue growth

5. clot dissolution

1. Inappropriate clotting within the vascular compartment.

2. Clotting insufficient to stop blood flow from the vascular compartment.

VESSEL SPASM

Initiated by ____ spasm.

Result of ___ and ____ mechanisms.

Constricts blood vessel→decreased blood flow

Typically lasts less than a minute, cute can last hours if needed.

PLATELET REVIEW

Formed in ____ as cytoplasmic ___ from _______.

Production is under the influence of ______ (hormone.)

It is processed through ___ for about 8 hrs before being released into  peripheral circulation

What is the life span?

What are normal counts?

PLATELET CHARACTERISTICS:

What factor is required to activate platelets?

What charge does a circulating platelet have before it's activated?

What factor is required to activate platelets? Von Willebrand Factor

What charge does a circulating platelet have before it's activated?

Negatively charged

Platelets contact injured vessel wall

-negative charge of cessel wall is lost, so the negatively charged plateltes adhere to the surface

Platelets become activated

upon activation, platelet surface becomes spiny, exposing surface receptors

Platelet functions

adherence and aggregation

adherence/adhesion

aggregation: form meshwork under influence of ADP, platelet activating factors such as thromboxane A and thrombin

CLINICAL NOTE:

Platelet deficiencies in number and/or function cause what?

increased capillary permeability resulting in

1. small skin/mucous membrane hemorrhages known as petechiae/purpura/ecchymosis

BLOOD CLOT FORMATION

Production of _____ fibrin.

occurs via _____ and ___ pathways. 

Requires activation and consumption of _____.

Production of insoluble fibrin.

occurs via extrinsic and intrinsic pathways. 

Requires activation and consumption of coagulation factors.

COAGULATION FACTORS

Procoagulants:

Factors I-VIII circulate in the blood in ____ form.

All factors are made in the ____ except factor ____.

Factors __, ___, ___, ____ are Vitamin K dependent for formation (as well as Protein __)

Procoagulants:

Factors I-VIII circulate in the blood in inactive form.

All factors are made in the liver except factor VIII.

Factors II, VII, IX, X are Vitamin K dependent for formation (as well as Protein C)

COAG FACTORS

Factor I → 

Factor II →  

Factor III → 

Factor IV → 

Factor I → FIBRINOGEN

Factor II →  PROTHROMBIN

Factor III → TISSUE THROMBOPLASTIN

Factor IV →CALCIUM

Antithrombin III

heparin

alpha2 macroglobulin

protein C

Stage I: formation of prothrombin activator

Stage 2: conversion of prothrombin to thrombin

Stage 3: conversion of fibrinogen to fibrin

Extrinsic: vascular wall and/or extravascular tissues damaged/traumatixed which causes release of tissue thromboplastin factor, activation of Factor X (you get cleaving of prothrombin to thrombin, mechanism accelerated with Factor V) and formation of prothrombin activator

Intrinsic: blood trauma or exposure of blood to vascular wall collagen causes 

activation of Factor XII and release of vWF, TXA2 and ADP

Facors XI, IX, VII (w Ca) activation leds to activation of Factors X and V

Prothrombin activator formed

What test is used to measure the extrinsic pathway?

What test is used to measure the intrinsic pathway?

What test is used to measure the intrinsic pathway?

aPTT/PTT

unfractionated heparin

What is the end product of both the extrinsic and intrinsic pathway?

This new activator allows for what?

CLINICAL NOTE:

Where is prothrombin formed?

What does it require for normal formation of Factor II?

Where is prothrombin formed? LIVER

What does it require for normal formation of Factor II?

requires Vit K

if no Vitamin K and/or severe liver disease causes decreased levels of prothrombin and results in bleeding via a coagulation defect.

antigen antibody reactions

some drugs and venoms

circulating cellular debris

retained placental fragments

...all of the above could cause what? (related to coagulation)

Consumptive coagulopathy

-platelets, coagulation factors get depleted because coagulation sequence is activated

-High mortality

Meshwork of fibrin fibers, RBC's, platelets and plasma

...these are all part components of what?

What is the function?

BLOOD CLOT

Function: vascular wall attachment of blood clot at site of injury/damage prevents blood loss

Protein C- inactivates V and VIII

Heparin- combines with anti-thrombin III cofactor to suppress the fibrin formation

antiphospholipd syndrome

increased platelet function (ie. atherosclerosis, smoking)

accelerated activation of coagulation system (ie. elevated estrogens, OCP's, malignant disease, post surgery)

all of these could cause what type of state?

_____ Disorder

Caused by vascular integrity (damaged/weak vessels)

Evidenced by purpura, petechiae

Examples:

Vit C deficiency

Hemorrhagic telangiectasia (Weber Osler Rendu)

Cushin's disease

heparin

quinine, quinidine

sulfa, penicillin

cephalosporin

What is the word for "abnormal platelet function?"

Name four causes.

thrombocytopathia

Causes:

Von Willebrand's disease

ASA

NSAID

Uremia

Aspirin

Warfarin: reverse effects with Vit K and fresh frozen plasma admin

Heparin: reverse effects with Protamine sulfate

Congential

Hemophilia A

Christmas Disease

Acquired

Liver disease

Vit K deficiency

Exsanguination

Cardiovascular shock

multiple organ failure

death

M phasE: replicated chromosomes separate and form two nucli by mitosis and cytoplasm divides between two nuclei by mitosis and cytoplasm divides btw to two cells by cytokinesis

G1 (gap 1) growth period when cell determines if its ready to commit to DNA synthesis

S (DAN synthesis) period during which genetic material replicated

G2 (gap 2): period during which DNA replication is checked and errors are corrected

cell growth is not regulated by external signals

cells have the ability to invade tissues

CANCER:

What's the difference between invasion and metastasis?

invasions: goes to neigboring tissues

Metastasis: goes to lymph nodes, blood vessels and distant sites

divide and differentiate

divide: ie stem cells

differeniate: no longer able to divide

G1: cell decides if ready for DNA synthesis

M: DNA replication occurs

G2: cell checks itself for accuracy and repairs errors

M phase: chromosomes replicate and divide via mitosis AS WELL as division of the cytoplasms via cytokinesis

GENETIC BASIS OF CANCER

Most cancers originate from a _____ cell.

Most mutations occur in ____ cells (_%)

Minority of cancers are ____ (_%)

1. Errors in DNA replication

2. Induced carcinogen exposure

3. Requires multiple genetic lesions

Majority of _____ mutations are _____ and most are due to _____

CML is due to _______

carcinogens

able to damage genome or disrupt cellular metabolic processes

Name the gene:

genes that promote normal cell growth and can be converted to oncogenes through mutations or increased expression.

EXAMPLES: RAS, WNT, MYC, ERK, TRK

Name the gene:

usually restrain growth with unregulated cell growth occurring when they malfunction.

• growth factors
• receptor tyrosine kinases
• cytoplasmic tyrosine kinases
• cytoplasmic serine/threonin kinase
• regulatory GTPases
• Transcription factors

This is a protein subfamily of small GTPases which function as on/off switches.

Involved in cellular signal transduction

This gene encodes for transcription factor.

Regulates expression of 15% of all genes.

Involved in Burkitt Lymphoma.

What is causing the following to occur to cells?

altered morphology

loss of contact inhibition

ability to grow without attachment

ability to proliferate indefinitely

reduced need for growth factors

high saturation density

inability to halt proliferation in response to deprivation of growth factors

increased glucose transport

tumorigenicity

Name the gene:

Ex of tumor suppressor gene

Dominant inheritance

germline mutation causes loss of function of one allele on chromosome 13

occasional sporadic cases are unilateral and caused by somatic mutations of both __ alleles.

This tumor suppressor gene can cause sarcomas, brain tumors, leukemia.

What syndrome is associated with the gene?

this video may help you remember it:

http://www.youtube.com/watch?v=PMe_w_EOasU

Tumor Suppressor Gene p53

Li Fraumeni syndrome

What is Lynch syndrome?

HNPCC: hereditary nonpolyposis colon cancer

conol cnacer in three or more individuals over at least 2 generations

-at least one dividual under age 50

-about 1/200 individuals have HNPCC

What is the relationship of apoptosis and cancer?

Loss of what gene can cause apoptosis to go haywire?

Tumors evolve ways to inhibit or disable apoptosis

Loss of p53 tumor suppressor gene

What do tumors require to receive adequate supply of oxygen, nutrients and removal of waste products?

What can you do to treat several solid tumors? (medication)

Cancer needs adequare blood supply so you need to stop angiogenesis

Bevacizumab is a monoclonal antibody against VEGF and used in tx of several solid tumors

What am i describing?

molecular or tissue based assay beyond routine clinical, radiographic or pathologic examination which predicts future behavior of cancer.

How are they measured?

Identified where? (4)

Biomarkers

Measured: DNA, RNA, protein, cell tissue

Identified in tumor tissue, lymph nodes, distant sites or blood

Risk determination (screening/prevention)

Screening (early detection)

Differential diagnosis (B-HCG, Alpha fetal protein for germ cell tumors)

Prognosis: risk of invasion and metasttasis

Prediction: how patient will respond to given therapy

Monitoring: CEA, CA 125, PSA

name the biomarker:

Proto-oncogene important in breast cancer.

Prognostically signals a  more aggressive cancer.

How is it measured?

name the biomarker: HER 2

How is it measured? Immunohistochemistry or FISH (fluorescent in situ hybridization)

Name 3 tumor markers for Breast Cancer.

Name one tumor maker for colorectal cancer.

Name one tumor maker for Pancreatic cancer.

**YOU DON'T DIAGNOSE WITH THESE; JUST GOOD FOR MONITORING!