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212 terms

patho test 2

STUDY
PLAY
immune system function
identifies antigens/pathogens and destroys them.

host is recognized and spared
nonspecific immunity
( innate)

rapid response- limited microbed

stimulates and buys time for second line of defense (adaptive response to prepare)
specific immunity
( adaptive)

sepcific recognition, amplified response to invaders

remembers

involves b and t lymphocytes REMEMBERS AGENT

humoral and cell mediated
antigens
invaders which cause immune response

usually large molecules

macrophages breakdown through phagocytosis

binding sites ( epotopes/antigenic determinants) emerge on broken antigen units

the unique shape of the epitope recognizes by either receptors on immune cells or by antibodies
apc
antigen presenting cell ( dendritic)
leukocyte
white blood cells
monocytes
largest leukocyte

mature in tissues ( liver, lung, spleen)

become macrophages

activated wtih either inflammatory stimuli or antigens

involved in innate or adaptive response

experts at phagocytosis

capable of priming specific immunity

FIRST TO MEET ANTIGEN

process and present antigen fragments to t cells for destruction
lymphocyte
principle cells involved in adaptive ( specific) immunity

differentiate into t and b cells

constantly circulate but return to concentrate in lymphoid tissues ( lymph nodes, spleen, thymus)
cardinal features of immune cells
self recognition

specificity

memory

self regulation

diversity
self recognition
keeps immune cells from destroying normal cells

healthy response against FOREING

major histocompatability complex
mhc
major histocompatability complex

unique set of proteins on cell surface that mark cells as " self"

this complex ( a protein) cradle antigens for presentation to t cells

human leukocyte antigen ( HLA)-= MHC controlled by chromosome 6

all play a role in immune function
histocompatability
refers to tissue compatability. determines whether organ transplant will be compatable

no two people have the same mhc except identical twins
mhc 1
displayed on ALL NUCLEATED CELLS AND PLATELETS

proteins protect against viruses or cancers that are intracellular

the antigen is engulged by wbc ( macrophages) and broken down inside the cell...pieces present on cell surface conntected to mhc 1

this presentation allows immune system to look at and read whether " self" or " non self"

if judged foreign attracts cd8 t cells which KILL the antigen ( cell mediated)
mhc 2
proteins connect with antigens OUTSIDE the cell and present those to t lymphocytes

if read by immune system and judge foreign helper t cells multiply and stimulate b cells to produce antibodies
( specific to antigen, HUMORAL)
specificity
ability to exactly recognize invader

design and implement immune response targeted to that specific invader

not like inflammation ( where the response is the same equal for all antigens...inflamation is nonsepcific)

specific response for each pathogen
memory
oncy lymphocytes stimulated by antigen they acquire memory
both t and b cells

remain in body a long time

allow for rapid response on repeated exposure to antigen

often so subtle we dont know its happening
self regulation
immune system carries out functions without direct input from other systems( brain doesnt need to say " hey start working"
diversity
ability to respond to different kinds of antigens daily
cytokines
intercellular signalling molecules or chemical messangers of the immune system

keep immune system working together

very low molecular weight proteins

present in both immunitites

can persist all over

influence the actions of other cytokines- cascades

very short half life. protects against excessive immune response

released at cell to cell interfaces

signals sent to cytoplasm of cells- induced genes to respond

one cytokine often has the ability of acting on more than one cell type
immunization
administration of vaccine
active immunity
achieved by immunization or actually having disease- requires you to make antibodies

depends on a response to the antigen by the person's immune system

long lasting, once established

requires few days to weeks after first exposure to develop sufficient immune response to destroy pathogen

subsequent exposures reacts in hours to the same agent due to memory b and t cells and circulating antibodies
passive immunity
immunity transferred from another source, you dont need to produce your own antibodies they are given

maternal igG passes placenta and provides infant protection for first month of life

when an infant recieves immunity from antibodies through breast milk

only short term protection, weeks to months

can be artificially transferred if given antibodies produced from someone else ( immune serum globulin- pool of antibodies from many people)

FIRST KIND OF IMMUNITY OUT OF ACTIVE AND PASSIVE
antibody mediated
HUMORAL

antibodies responsible for enhancing/ fostering antigen destruction

usually actiavated by bacteria bacterial toxins, free viruses, EXTRACELLULAR PATHOGENS


activate b lymph
two types of responses primary and secondary
primary immune response
first exposure to antigen

lagtime- before antibodies are detected in blood

allows for processing of antigen by apc( machrophages or dendritic)

allows for cd4 helper t cells to recognize antigen cradled on mhc2 protein on cell surface

helper t cells are activated and stimulate / direct the rest the immune system MASTER SWITCH

this triggers b cells to proliferate and differentiate into plasma cells

these plasma cells produce antibodies or memory cells

activation of this response takes 1-2 weeks detectable antibodies will continue to rise for several weeks

recovery from many infections occurs during primary response when antibodies have reached peak in blood
secondary immune response
MEMORY

secondary exposures

memory cells remain in body for a long time, ready for action

remember the invader and cause rapid reaction ( antibodies quick to area) on next exposure

antibodies rise sooner and reach a higher level due to memory cells

booster shot
plasma cells
formed by b cells

can secrete thousands of proteins called antibodies per second ( immunoglobulins)

these antibodies attach to foreign antigens

causing destruction of antigen by :
- clumping togehter
- lysis ( break down)
-neutralization
-facilitation phagocytosis
-activation of complement system
immunoglobulins
during an antibody mediated ( humoral) response

b lymph ( plasma cells) form antibodies to combat the antigen
igM
first antibody type made by newborn

FIRST TO APPEAR IN RESPONSE TO ANTIGEN

presence indicates in utero or newborn infection
igA
found in saliva, tears, colostrum, bronchial, prostatic, vaginal, gi

pprotects against infection in mucosal tissue
igD
found on b lymphocytes
NEEDED FOR MATURATION OF B CELLS
igG
MOST ABUNDANT

only one that crosses the placenta from mother to infant

protects against bacteria, toxins and viruses
igE
binds to mast cells and basophils

INVOLVED IN ALLERGIC REACTIONS AND HYPERSENSITIVITY

combats parasites
memory cells
created after initial exposure to an antigen, aquire memory
cell mediated immune response
invader living INTRACELLULARLY

invaders live inside body's cells ( antivodies cant penetrate the membrane)

both cd4 and cd8

antigens displayed on mhc1

cd8 induce apoptosis of infected cells-perforin secretion to punch holes in membrane

sensitized cd8 cells make clones that recognize other similarly infected cells and target those for destruction

activated t cells can also generate primary and secondary cell mediated immune responses ( humoral)

t cells also have memory
what is a complement
complements/enhances both innate adaptive defensives

a complex cascade of interdependent antimicrobial plasma proteins

circulated in blood in an inactivated form

when activated they can mark cells for destruction or promote inflammation

deposit protein fragment on pathogen ( tags) phagocytes then locate and destroy
immune system regulation
self regulation

when out of order
-inadequate response ( HIV)
-inappropriate response ( autoimmune)
- excessive response ( allergies)
innate immunity
( nonspecific)

inflamation,

protective in nature

eliminates cause of cell injury and necrotic cells

leads way for healing

physiological events similar regardless of cause location or extent of tissue injury
cardinal signs of inflamation
heat-calor
redness-rubor
swelling-tumor
pain-dolor
loss of function- functio laesa
systemic inflammation
generalized vasodilation due to infection

swelling, fever, bacterial count, high inflammatory cytokine levels
vascular stage
first stage of acute inflammation

begins with injury and results in momentary vaso constriction

followed immediately by vasodilation of arterioules and venules- which increasess capillary blood flow and results in redness and warmth

increase in vascular permeability- this causes protein rich fluid to move into the extravascular spaces creating an accumulation of fluid in the tissue ( results in swelling, pain and impaired function)
cellular stage
second stage of the acute inflammatory process
granulocytes
60-80 percent of total number of wbc

derive from myeloid stem cells in marrow and mature in the marrow
basophils
stain blue

precursors to mast cells

granules in the cytpolasm secrete histamine which is responsible for the symptoms of inflammation ( redness and swelling)
eosinophils
inolved in allergic responses and parasitic infections

present in chronic inflammation
neutrophils
most numerous leukocyte

first phagocytic cell to arrive at site of invasion ( within 90 minutes)

life spam-24-48 hours
bands
immature neutrophils

increase when excessive demand for phagocytes
mmonocytes
live 3-4x longer than granulocyte ( netrophils)

largest of all wbc

experts at phagocytosis

signal specific immune response to begin

predominant cell by 48 hours

play important role in chronic inflammation-( wall off material that cant be ingested)
event 1
cellular sequence of events during inflammation

margination ( pavementing)

as fluid seeps out through capillaries

blood becomes more viscous

wbc move to periphery of the vessels and adhere to capillary endothelium
event 2
cellular sequence of events during inflammation

emigration ( transmigration)

wbc move through vessel walls by ameboid action into the tissue spaces
event 3
chemotaxis

damaged tissues

agents send out cytokines

oull wbc to damage areas
event 4
phagocytosis

foreing agents engulfed and destroyed

done mostly by neuutrophils and macrophages
inflammatory mediators
responsivle for the signs and symptoms of inflamation
( histamine, bradykinin, prostaglandins, leuotrienes)
exudate
fluids that have escaped blood vessels

destroyed wbc, rbc, fluid
serosanguineous
mixture of rbc and plamasma
purulennt
contains pus ( degraded wbc proteins, tissue debris)

odor and color depend on organism
serous
watery, low protein

result when plasma enters site
fibrinous
form sticky meshwork

walls off infection
hemorrhagic
severe tissue injury causes damage to vessels

leak of rbc from capillaries
acute inflammation
occurs moments after injry

subsides quickly

self limiting
chronic inflammation
long term

self perpetuating
immune deficiency
deficient or underactive immune system
hypersensitivities
over active immune system
autoimmune disorders
loss of self recognition ability, immune system destroys host
aids
acquired immunodeficiency syndrome

profound immunosuppression with association opportunistic infections

malignancy
hiv
human immunodeficiency virus

selectively attacks cd4 t cells

deteriorating immune system

pandemic

33 million people live with hiv/aids

women and young-50% of infections

not standard reporting
hiv transmision
exchange of blood/ body fluids that contain the virus or virus infected cells

( blood, semen, vaginal secretions, breast milk)
sexual mode of contact
most frequent for transmission

oral, anal, vaginal intercourse is risky

men/memn 53%

men/women 32- high risk

greater risk when mucosal surfaces not intact ( std)
blood to blood contact
needles, syringes contaminated with blood leads to direct route for transmission

.3 risk
perinatal contact
transmission from mom to child most common childhood infection

can occur in utero, during delivery, or thru breast milk
occupational contact
universal precautions
other std/sti
increased risk for hiv

increased severity of other stds

drug abuse
risk factors in essence
risk for infection exists when exposed to infected blood semen or vaginal secretions are deposited onto mucous membranes or into blood of another
risk factors no transmission risk
casual contact, mosquites or insects
hiv blood transfusion
screening after the 1980s

screened for p24 antigen
seroconversion
when a person converts from negative to positive

takes 1-3 months after exposure, can take up to 6 months
window period
time after infection before positive

there are no physical signs however person is highly contagious
hiv/aids pathogenesis
begins with hiv

retrovirus, infects cd4
hiv1
most common form in us associated with aids
hiv2
most common form in western africa

slower progression
step one viral replication
attachment-
virus binds to cd4 cell
step two viral replication
uncoating and internalization-
virus uncoats itself

core content ( viral rna, and reverse transcriptase) enter cell

allows for more hiv production
step three viral replication
dna synthesis-
reverse transcriptase changes viral rna to viral dna
step four viral replication
integration-
viral dna enters nucleus of cd4 cells inserts into original dna
step five viral replication
transcription-
viral dna transcribed, changed into messenger rna
provides instructions for building viruses
step six viral replication
translation-
use instructions
create proteins and exymes ( polyproteins) - these support new viral construction
step seven viral replication
cleavage-
polyproteins broken down to individual protein for new viruses
step eight viral replication
assembly-
viral rna and proteins assembled to new viruses released from cd4 cell
acute phase hiv
primary infection

fever, fatigue, myalgias, sore throat, night sweat, gi, lymphadonopathy

incrased viral load, decreased cd4

1-4 weeks after exposure, lasts for 7-10 days
latent period hiv
chronic infection

no signs or symptoms

decreased cd4

10 years
overt aids
8-10 years to reach

cd4 lymph <200 respiratory gi wasting metabolic cancers
cd4 decrease load increases

2-3 years
viral replication results
cd4 cells killed ( million per day)

hiv copies released into blood ( billions)

invade next cd4 cell
overtime cant keep up viral load increases cd4 decreases
opportunistic infections
infections the immune system could normally get rid of , in hiv/aids causes greate damage

pneumosistis corinii pneumonia - most common

jiroveci coninii-humans

risk greatest when cd4 cells are at the lowest <200
mycobacterium tuberculosis
hypersensitivity disorders
excess or inappropriate immune system activation

results in injury and death
type 1 hypersensitivity disorder
antivodies involved are igE

b lymph

allergic reaction usually environmental cause
( inahaled, injected, ingested, skin contact)
type 1 hypersensitivity example
person exposed to ragweed
igE antivodies attach to mast cells
second exposure IgE primed mast cells -degranulate and release chemcials
- histamine, complement, ( stimulates inflammatory response) acetylcholine ( broncial smooth muscle contraction)
atopic hypersensitivity
genetic
most common in LOCALIZED RESPONSE

common environmental allergens

hay fever, and allergic asthma

food allergies, and dermatitis less common

leads to sneezing, swelling and eye redness

ANNOYING
nonatopic hypersensitivity
systemic response
more serious than the other two

lacks genetic component

not organ specific

ANAPHYLAXIS

immediate response
- vasodilation
-increased capillary permeability ( results in hypotension, or anaphylactic shock)
-blood pressure decreases due to leakiness
-smooth muscle contraction and bronchial constriction
-sense of foreboding
-itching palms, hives, swelling of eyelids, lips, tongue, feet, uvula, and larynx
-air hunger, stridor, wheezing
type 2 hypersensitivity disorder
cytotoxic reaction
antibodies involved are igG and igM attack antigens on cell surfaces

activation of COMPLEMENT SYSTEM
set of 20 plasma proteins
results in phagocytosis and cell lysis

usually involves antigens on rbc or wbc- transfusion reactions or certain drug reactions
incompatable blood
type two hypersensitivity disorder

blood gets coated with igG or igM
- targeted for destruction by macrophages
-complement activated and results in lysis
-transfused rbc
type o
no a or b antigens on rbc surface

a and b plasma

UNIVERSAL DONOR (no antigens present on cell surface of these rbc, no type of antibody present in a recipients blood would react with this donated blood)
type a
a antigens on rbc surface
b antibodies in plasma

transfuse with a or o
type b
b antigesn on rbc surface

a antibodies in plasma

transfuse with b or o
type ab
both a and b antigesn on rbc surface

neitgher a nor b antibodies

transfuse with abo

UNIVERSAL RECIPIENT
type three hypersensitivity
immune complex disorder

- formation if igG and igM antibody/antigen immune complezes

complexes accumulate in capillary walls

leads to activation of the chemical mediators of inflammation ( histamine)

neutrophils attracted to area
- attempt phagocytosis , cause immune complexes to release enxymes which cause further tissue damage
type three hypersensitivity example
strep throat infection, antigen binds with igG and igM in circulation to form immune complexes

complexes accumulate in glomerular basement
type four hypersensitivity
cell mediated

antibodies not involved-T CELLS INVOLVED
- react with antigens and release lymphokines ( draw macrophages to area) causing tissue damage

two sub types
direct cell mediated cytotoxicity
type 4 hypersensitivity sub type 1

when intracellular pathogens ( viruses) or extracellular agents ( fungi and protozoa)

cd8 cytolytic t cells directly kill antigen
- with some infection antigen itself not harmful
-cd8 cells cant tell difference so they kill all infected
--sometimes tissue damage that results is really due to cd8 response and not due to invader
delayed hyper sensitivity response
type 4 hypersensitivity sub type 2

occurs 24-72 hours after exposure of sensitized person to offending antigen ( delayed reaction)

cd4 t cells involved

example ( tb, poison ivy)
autoimmune disorders
inability of immune system to recognize self from nonself

immune response mounted against host tissue

leads to localized or systemic injury

can affect any tissue of body

immune unable to use HLA surface markers to determine foreign from host
autoimmune disorders-etiology
viruses, genetics, gender

if you have one auto disease more prone to others

often associated with abonormal stressors
major components of hematopoietic system
bone marrow- where blood is formed

blood cells- rbc, wbc, platelets

lymphoid tissue
puripotent stem cells
all blood cells derived from these

potential for proliferation and self renewal for life

source/resource for all blood cells
myeloid stem cells path
paths of differentiation

cells formed, maturation and differentiated in bone marrow

generates precursors to
-erythrocytes
-granulocytes
-monocytes/macrophages
-platelets
lymphoid stem cell path
cells formed in marrow but generally mature to some lymph system ( thymus)

generates precursors to b and t cells
red blood cell
up to 1000x more numerous than other blood cells

non nulceated biconcave disks

transport oxygen to tissues via hemoglobin

binds some co2 in tissues and brings it back to lungs ( exhale)
adult hemoglobin
2 pairs ( 4 seperate) polypeptied chains ( alpha and beta)

heme component- pigmented iron containing portion, binds with o2

globin- protein

each hemoglobin molecule can carry 4 o2

with hemolysis iron and protein recycled
- heme changed to biliruibin and eliminated
-lack of iron means decreased hemoglobin synthesis
rbc life cycle
120 days
oxyhemoglobin
fully saturated bright red
deoxyhemoglobin
not fully saturated with o2-blue purple color
fetal hemoglobin
present from 3rd-9th month gestation

alpha chains substituted for gama chains that allow for a greater affinity for oxygen( 6 months after birth changes to adult)
erythrocytes
mature rbc

enter blood stream before they are fully mature ( reticulocyte)
proerythrocytes
precursors to rbc come from pluripotent stem cells
IT TAKES ONE WEEK FOR AN IMMATURE RBC TO BE FORMED AND SHOW UP IN CIRCULATION

1% of rbc in immature stage

IT TAKES 24-48 HOURS FROM RETICULOCYTE TO RBC
erythropoietin
hormone released by the kidneys that stimulates the production of rbc

governed by tissue oxygen needs
red blood cell destruction
normal lifespan 120 days

normally the rate of production and destruction are equal ( 1% made 1% destroyed)

macrophages in liver, spleen, bone marrow, and lymph tissue destroy rbc

amino acids are saved from globin chains

iron saved from heme
lytic
break down
bilirubin
insoluble plasma, unconjugated ( indirect) (what heme is first converted to )

travels to liver where it is changed to soluble (bile) ( direct/conjugated)

too much unconjugated bilirubin builds up when levels exheed liver's ability to remove it ( jaundice)
red blood cell count
total number of rbc in 1 mm of blood

NORMAL 3.6-5.4 MILLION
reticulocyte count
provides an index of rate of red blood cell production

normally 1% of rbc
hemoglobin
MALES 14-16.5 FEMALES 12-15
hematocrit
percentage or rbc in plasma

varies with quantity of extracellular fluid ( increases with dehydration)

MALES 40-50 FEMALES 37-47
rbc indicies
help to differentiate/classify type of anemia
mean corpuscular volume
mcv

reflects the volume of size of rbc

falls with microcytic anemias, grows with carcocytic anemias
normocytic
rbc of normal size
mean corpuscular hemoglobin concentration
refers to concentration of hemoglobin in each cell

accounts for the color of rbc
normochromic
rbc of normal color
hypochromic
decreased color
anemia
low number of circulating rbc

low level of hemoglobin

or both
anemia possible etiology
excess blood loss

excess rbc destruction ( hemolysis)

decidient rbc production
anemia cosequences
decreased o2 carrying capacity

tissue hypoxia ( if not treated)
anemia manefestations
depend on its severity, the rapidity of its development, underlying pathologic conditions and the age and health status

if onselt is slow, body compensates for the drop in o2 carrying capacity of the blood with an increase in plasma volume ( heart works harder, it does this to increase blood flow to tissue) cardiac output( more blood pumped out tachycardia) and resporatory rate( take in more o2)

pallor of skin and nailbeds
- redistribution of the blood from cutaneous tissues or lack of hemoglobin
-body aims to pump blood to vital organs -skin pale
tissue hypoxia signs and symptoms
weakness and fatigue
hemolytic anemia
blood breakdown

premature destruction of rbc

retention of iron-good

results in increased erythropoiesis ( kidneys try to compensate)
hemolytic anemia indicies and labs
normocytic rbc

normochromic rbc

increased reticulocyte count ( premature destruction of erythrocytes reticlocytes released)
hemolytic anemia clinical manifestations
typical of anemia ( fatique and weakness)

bilirubinema ( jaundice)
hemolytic anemia causes
extrinsic ( acquired) - things outside tbc itself ( drugs, bacteria, toxins)

intrinsic ( inherited)- conditions hwere there are defects in rbc membrane or hemoglobinopathies ( sickle cell)
blood loss anemia
if blood loss is rapid circulatory shock and collapse

-bp decreases, pulse incresase, resporatory rate increases

can lose gradually 50 percent without symptoms

if bleeding is controlled and iron is god 3-4 weeks to replenish

external bleeding equals loss in iron
chronic blood loss
does not affect blood volume

usually causes iron deficiency anemia

normally free of symptoms until <8

microcytic hypochromic rbc involved
sickle cell anemia
hemoglobin is altered in sickle cell , caused by mutation of beta chain aa substituted for valine

mostly affects african americans

.1-.2 in us affected by sickle cell disease

8% heterozygous affected by trait

inherited by ressessive inheritance

40% abnormal hbs heteroxygote

80-95% hbs in sickle cell disease ( homo)
hbs
the higher the concentration the higher the risk of sickeling

it polymerizes when deoxygenated creating a semisolid gel that make erythrocyte rigid
- distorts shape and causes structural damage to rbc membrane

can return to its normal shape with oxygenation but if episode of deoxy repeated they are permanentrly sickled

infants dont experience until they are 8-10 weeks because of fetal hemoblobin

sickle cell trait has less hbs generally asymptomatic
sickling consequences
premature destruction of rbc leading to chronic hemolytic anemia

average sickling rbc lifespan is 20 days

vessel occulusion
-this disrupts blood flow and causes ischemia and pain crisis
factors that enhance sickling
cold, stress, physical exertion, infection and illness ( hypoxia, acidosis, dehydration)
iron deficiency anemia
microcytic anemia

deficiency of iron

impaired o2 delivery
iron deficiency anemia causes
chronic blood loss- most common cause for adults

iron normally recycled with chronic blood loss iron also lost in menstration , gi bleeding

dietary usually not a problem in us

we absorb .5-1.5 per day
iron deficiency anemia increased demand
pregnant women- blood volume expands need more iron

lactating women

infants toddlers- increased growth increased blood volume

adolescents- menstration, growth spurts
iron deficiency anemia - labs and indicies
decreased hemoglobin and homatocrit

decreased ferritin ( stored iron) levels

decreased rbc

microcytic

hyochromic

decreased mchc

decreased mcv

irregular shape

irregular size
vitamin b12
megaloblastic anemia- enlarged but poorly working

abnormal dna synthesis

impaired rbc maturation

eventual drop in rbc numbers

develops slowly, usually very few early symptoms
vitamin b 12 deficiency causes
dietary- rare

pernicous anemia
- occurs with immune disorder, chronic atrophic gastritis
-destroys gastric mucousa and parietal cells which normally secrete intrinsic factors

intrinsic factor joins with b12 travels to illium where absorption occurs

parasthesias
b12 labs and indicies
increased size

oval shape

mchc normal

cell membrane flimsy

life span short
folic acid deficiency
also megaloblastic

results in abnormal dna synthesis and impaired rbc maturation

eventual drop in rbc production

slowly develops few early symptoms
folic acid
greens, fruits vegies

normally absorbed in intenstines

especially important for neural tube development of fetus
folic acid indicies and labs
increased size

oval shape

increased mcv

normal mchc

cll membrane flimsy

life span short
aplastic anemia
bone marrow depression fails to replace senescent cells...cells in circulation remain normal

decrease in all hematopoietic lines ( pancytopenia)

drop in rbc, platelets, wbc

marrow replaced with fat

pan " across the board"

Cyto " cell"

penia " drop"
aplastic anemia causes
unknown in 2/3 cases idiopathic aplastic
-radiation
-chemicals ( benzene)
-chemotherapy and irradiation
-antibiotics
-viral infections ( mono, hiv, hepatitis)
idopathic
we dont know the cause
aplastic anemia indicies and labs
normal size

normal color

decreased number

decreased wbc and platelets
hemostasis
normal- stepwise process for stopping bleeding
5 stages

abnormal- clotting insufficient to stop blood flow from cascular compatment
hemostasis major cells
platelets ( thrombocytes)
- circulating cell fragments of the large megakaryocytes
NORMAL COUNT 150,000-400,00
only 2/3 of platelets circulate at any time ( others stay in spleen)

essential for clotting
stage one hemostasis
vessel spasm-

first line of defense

starts with injury to vessel wall ( endothelial lining)

spasm, constriction, reduced blood flow

lasts <1 minute
stage two hemostasis
platelet plug formation-

second line of defense

platelets contact damaged vessel wall

plug enough to stop bleeds if damage small
platelet adhesion
step one of platelet plug formation

platelets swell, get sticky, change from smooth disks to spiny spheres

adhere to subendothelial layer of vessel wall of injury

for adhesion to occur must have von willebrand protein
platelet aggregation
step two of platelet plug formation

platelets released contents of their granlues (adp thrombazane)

cause platelets to attract and attach to each other

process still reversible platelets not cemented " primary hemostatic platelet plug"
stage three hemostasis
coagulation cascade-

if bleed large coagulation cascade ( platelets surfaces) activated

domino effect, once started only stops when platlet plug cementric ( fibrin meshwork) " secondary hemostatic plug"
intrinsic secondary hemostatic plug step
slow process, many steps

when damage within vessel, de to blood contacting collagen of injured vessel wall

defects in this path results in more severe bleeding than extrinsic path defects

both come together at factor 10
extrinsic secondary hemostatic plug step
fewere steps than intrinsic fast SECONDS

bleeding not as severe as when defects in intrinsic path

when tissues are injured a cellular lipolprotein is exposed. activates pathway
final common pathway
although they start from different points ( intrinsic and extrinsic) both paths have same final steps

activation of x factor

prothrombin to thrombin

fibrinogen to fibrin

formation of stable clot
coagulation cascade control
delicate balance between procagulation factors and anticoagulation factors

procoagulation and anticoagulation factors
procoagulation
promote clotting identified by roman numerals

each performs specific steps in coagulation one activaes the next ( cascade)

most always present in blood just not active

calcium ( factor 4) required for all but first two steps
anticoagulation
keep clotitng process balanced

prevent uncontrolled thrombus formation

antithrombin 3 inactivates coagulation factors and neutralizes thrombin
stage four hemostasis
clot retratction-

normally occurs 20-60 minutes after clot formed

once clot stable platelets contract

serum squeezed out, edges of broken vessel brough together

requires large number of platelets
stage five hemostasis
clot dissolution ( fibrinolysis)-

clot break down

shortly after clot formed

blood flow re established

tpa tissue pasminogen activator released from inured tissues

plasminogen always in blood but active converted to plasmin

plasmin digests fibrin and factors

continues until clot dissolved
NORMAL PLATELET COUNT 150,000-400,000

NORMAL LIFESPAN 8-9 DAYS
thrombocytopenia
decrease in the number of circulating platelets to a level <100,00

platelet number must drop beneath 20,000 before spontaneous bleeding

most common at intracellular unctions, skin, mucous membranes, gi, oraphices, nose , ear, vagina
pupura
larger areas of purple bruising
causes of thrombocytopenia
decreased platelet production

decreased platelet survival

spleen sequestration

dilution
hemophilia a
x linked recessive ...mainly effects males

mutation in the factor 8

severity is determined by amount of normal 8 circulating
coagulation cascase
severe hmophelia has less than 1% or less of 8
mild 6-30 moderate 2-5

bleeding most common in gi, hip, knee, elbow, and ankle
granulocytes
wbc
includes neutrophils, eosinophils, basophils
monocyte/macrophages
wbc
lymphocytes
t and b and natural killer cells
leukemia
abnormal decrease in wbv <4000

NORMAL WBC 5,000-10,000
neutropenia
decrease in neutrophils 1500
normally compromise 50-70 wbc count
lymphoma
diverse group of solid tumors composed of neoplastic lymphoid cells. malignancy n peripheral lymph
bimodal
affects two different age groups
hodgkins disease
enlarged painless, node above diaphragm

15-40 and 55+

fever, chills, night sweats, pruitis

for a definite diagnosis, reed sternberg cells must be found
hodgkins stage a
lack of constitutional symptoms- fever weight loss fatigue
hodgkins stage b
if 10% weight loss over 6 months or night sweats present
reed stemberg cell
a malignant b cell

they may be present in other lymphadenophaties but is classic to hodgkins disease
non hodgkins lymphomas
any non hodgkins lymphatic neoplasias

three times more common

5th most common maligancy in men and women of older ages
non hodgkins etiology
unknown in most cases

possible viral cause ( mono)

hiv

herbicide, chemical exposure

malignant transformation of normal lymphoid tissue at specific stages of differentiation

can affect t or b cells

insidious onset

affects central ( bone marrow, thymus) or peripheral ( nodes, spleen) lymph tissues
non hodgkins manifestations
most originate in nodes

have potential to spread thru lymph system especially to lover and spleen and marrow

usually painless superficial lymphadenapothy

incrased susceptability to infections
leukemia
malignant neoplasia of cells orginally derived from pluripotent stem cells
- genetic alterations of dna of cells
- earlier in the differentiation process, th emore malignant
with leukemias single cell undergoes transformation and leukemic cells then proliferate
leukemia etiology
exposure to radiation, benzene, antitumor drugs

second cancer after aggressive chemo ( hodgkins)

genetics - downs, and familiar predisposition
leukemia pathogensis
diffuse replacement of bone marrow with
-unregulated
-proliferating
-immature
-neoplastic cells

leukemic cells spill out into blood
leukemia overal manifestations
neoplastic cells proliferate readily and function poorly. prevent maturation of normal cells in marrow

-decrease wbc- infections
-decreased rbc-anemias
-decrease plat-bleeding
two ways to classify leukemia
predominant cell type
- lymphocytic or myelogenous

acute vs chronic
lymphocytic leukemias
involve immature lymph and their progenitors that originate in marrow but infiltrate other lymph tissue
myelogenous leukemias
involve pluripotent myeloid stem cell in marrow

do interference with maturation of all blood cells
acute leukemia
cancer of the hematopoietic stem cells there for poorly differentiated cells

sudden onset

blasts ( immature) cells in circulation
chronic leukemia
move insidious onset

cells more different but function poorly
blasts
a blast is an immature wbc

there are small number of circulating blasts
acute lymphocytic leukemia
most common leukemia of childhood

accounts for 80-85 % of childhood leukemias

peak incidence at 2-4 years
acute myelogenous leukemia
mostly in (60-65)

strongly linked with toxins

type associated with downs
chronic lymphocytic leukemia
slow , chronic course

older aldults ( 10% younger than 50)

proloferation and accumulation of relatively mature lymphocytes but function poorly

malignant cell line primarily b cells in us
chronic myelogenous leukemia
15-20 percent of all leukemias in adults

mostly disorer 30-50

associated with presence of Philadelphia chromosome
- abl gene translocates to bcr genes and fuse together
-abl bcr fused gene functions as protooncogene results in cml