Pathology
Anatomy and Physiology
physiology: study living organisms
cells→tissue→organs→systems
bio processes of living things (metabolism, circulation, respiration) how contribute to health and homeostasis
homeostasis→ baseline/balance/equilibrium
think bp
Pathophysiology
study of abnormal ohysiological processes
disease and injusy
what causes
stress, trauma, injury
The cell and disease
diseases begin with something wrong with structure/function of cell, cause changes that can be detected and monitered
Stress and Adaptation
cause of pathology
what is stress
physical/ emotional response to demand/challenges
increase in heart rate (physical activity= challenge), increase in demand
fear/anxiety, change in climate, privation (something use to being there isnt anymore), joy/excitment, physical activity
affect normal cell funciton, cell must adapt to maintain fucntion
no maintain=injury/maladatptive changes
when respong/try to maintian function price to pay
how do cells adapt
atrophy, hypertrophy, hperplasia, metapalasia, dysplasia
atrophy: waste away/ degeneration of cells, dont use it you lose it think muscles and lack of use
hypertrophy: cells get bigger
physiological: cell got bigger but has support to do so (cardiac muscle increase in size as athlete work out)
pathological: cell bigger in size but no support increase (hypertension, enlargement of the heart)
basic cellular adaptations
hyperplasia: too many cells growing, in response to horomonal stimulation ( think preg and enlargemd breast tissue bc of estrogen)
only in cells capable of mitosis
can be maladaptive bc of genetics, cell number increase too much ( keloid formation)
metaplasia: cells change bc of genetic reprogramming to ensure survival ( one cell type to another)
think gerd: lower esophagela cells transform from squamous epithilium to columnar mucois producing cells because of stress in order to protect from splashing acid
if treat and get rid of stress can change back, somewhat reversable
dysplasia: cells have adapted (maladaptive) non reversebal
deranged cellular growth, cells stressed→ dont work right→ become deranged and strange
dna mutation/chronic inflammation (precancerous condition)
cells vay in size shape and organization
neoplasia cancer: new growth, disorganized and uncoordinated, cancerous bc dna mutation
Mechanisms of cell injury
cells adapt and try to mainatain fucnton but get hurt
physical injury
something ohysically happen to cell
hypoxic
no/low oxygen, happen often bc of decreased bloodflow
no blood to cell
aerobic metabolism stops (krebs cycle, atp production)
potassium leak out sodium leak in, mess up e gradient for electric potential activity, k na pump doesnt work with no atp, sodium stays in cell, cell swells, cell loses ability to function
if not using aerobic metabolism stwitch to anaerobic metabolism
end product is lactic acid, bad cfor cell,s damage cell membrane/mitochndria/structure
double edged sword: hypoxic injury, low blood flow, anaerobic metabolism, lactic acid , two bad things happening
metabloic things happening in body, make waste and manage, need to get rid of, overuse metabolism create too much waste and start to damage cell
use lots of resources/metabolic waste
free radicals (weird types of oxygen, cause damage to body), as form throughout day get rid of unless overdue
molecules with unpaired electron on outer shell, unstable (atom like to have even number e on outer shell, will steal and damage other )
usulayy get fixed by antioxidants inhibit action of
free radicals mess with other cells make more free radicals, xidative stress is damage when body cant keep up with waste formation (ROS)
damage to cell, dna, vital organs, lipid peroxidation (mem surround mitochind)
Antioxidants
inhibit activity of excess waste ROS ,packages in peroxisomes
enzymes and vitamins, works unless unreasonable
antioxidant supplements in clinical studies had no benefit and may be harmful
causes cell damage
cell makes antioxidants on location atht eh time, not in pill
Calcium Damage (ischemia)
cells usually mantian low intracellular calcium
busy ion, involve in many metabolic process, so active dont want too much in cell
will start things in cell prematurely, only let in cell when ready for it
sometimes too much extracellular calcium get in bc cellular damage/no atp, start processes and uses up atp cause cell damage
calciu will open gates to allow more calcium in, calcium cascade, the worse it gets the worse it gets
Cell is injured, if reverisble: cell heal and recover and back to work
may get pulled out apoptosis and program cell removal, or just die (necrosis)
cell injury reversible
cell heal itself, direct injury, water move into cell and disrupt
bleb out piuching, cell membrane stretched out of shape, cytoskeleton cllapse, all organelles swell ans stop funciton
reverisble bc nucleus is ok and can have info to fix the cell
sometimes not reversible, necrotic cell death (ishcemia no blood flow, toxic, mechanical injury)
cell rupture and contents spill into surrounding area, trigger inflammatory mediator
nectroic cell damage rest of cells around it, shrunken nucleus means pynknosis, degraded nucleus = karyolysis
tissue infarction: too much cellular death, prolonged ischemia
myocardial infarction, cardiac muscle no blood flow and die
decrease blood flow cause death of that tissue
apoptosis: programmed cell death
damage or worn out cell is very quietyly taken out of line and gotten rid of, no cells bothered
activate capspases, lysosomes with enzymes that begi process apoptosis, break down protien and dna
no infmammation, debris engulf by wbc
initated by: normal wearing out of cell
loss of survival signals, mitochndrila damage/dna damage
if old and worn out go apoptosis
telomere too small cause apoptosis
survival signals (cell talk to one another, tissue too big, cell cant get message, cell gets old and
mitochndiral damage
energy source damage, cell will die (ischemia/toxins)
Gene P53
repair dna damage, look for trouble and repair, will fix cell if fixable, cell alive but no funciton properly will just live, sometimes initiate apoptosis
gene P53 can not fix and start apoptosis in dna damage cell, cell will keep reporducing→ malignant tumor
Necrotic tssue
cell death and degredation
can undergo liquificatio, coagulation, infarcation, caseous necrosis
cell ontents release, causes inflammation
liquifaction: causes to slough away, caseus necrosis causes holes (cheeselike)
Gangrene: large area necrotic tissue
dry: lack arterial blood supply but venous flow carry fluid out tissue, coagulate
wet gangreme: lack venous flow, fluid accumulate, tissue liquefy and infect
gas ganrene: clostriduim infection porduce toxins and H2S bubbles (hydorgen sulfide bubbles in tissue)
Stress Response
alarm→ stresshoromones→ body wide changes
eustress: stimulte person in positive way
distress: stimulate perosn in negative way, hysical and emorional
whole boyd respond
Acute stress: happen intermittenltly, specific thing cause stress and will be relieve d when go away
chronic stress: prolonged activation of stress response, linked to cancer, immune suppresion, plarkinsosn, depression
Hans Selye: general adaptive syndrom
descibed as coordinated response to stressor, sawy innate adaptive ability to maintain hmeostaiss
alarm, resistance, and exhaustion
General Adaptation Syndrome
when have stress body will respond (horomones)
4 system activate:
cotricol )adrenal cortex)
epi and norepi(adrenal medulla/neurons
sns activation
antidiuretic horomone (adh come from posterior pituary
renin angiotensis aldosterone : kidney/adrenal contrec
cortisol: regulate stress repose, divert metabolism so no build tissue to supllying enegery for dealing with stress, cause sign/symptom of chrinic strss
release causes incrwde blood sugar, stronger symp system effect on heart, use energy in activity like hormones, anabolic activity and repdoductive functons, bone formation, rwb and wbs protection, immun systme. become depressed
Emergency activity: epi and nor epi (adrenaline/nor adremalin)
increase hr, periheral vasocontriction, everything peripheral force blood bakc to heart blood and brain, blood pressurengo up, lack of blood flow to internal organs, cause kidneys to stop working
sympathetic system: stress repsonse
rapid resoponse to trauma/emrgency, attach to adreklin and nopepineprhim, both attach onto adgrenergic recpetos on cells
blood prssure restoured, flow back to skin/guts/ kidney reduce, skin apale. urine production decreases, GI activity decreades
ADH: antidiureitic horomone, cause peripheral vasoconstricution, kidney reabosrb water into blood from urine
RAA: renin angiotensin aldosterone: activated by symp system, decrease bf, angiotensis converting ezye=me, angiotensin, stronger vasocontricton ( II)
stimulate adrenal contrex, aldosterone release, kidney reabsorb sodiuma dn water, excrete K+
PAtient Assemsment s/p MVA
increase heart rate, no urine production, no bowel sounds, pale/sweaty skinm low blood pressure, dilated pupils, elevted blood glucose
priority is low blood pressure, epi and nor epi are working to restore, give him fluid (iv) and blood bc fluid level is low
Response to stressor
Neoplasia: A Disorder of Cell Proliferation and DIfferentiation
cancer: patients come for problem also have cancer
prevalence of diagnosis: breast and prostate, dying of lung and colon
Cell cycle
Go cell: resting cell, cells activley doing cell stuff, get signla to divinde→ g1 phase (protiens and resources to grow and divide)→ S phase, gathered stuff and now synth dna→ g2 phase, cell snth structures to seperate→ then splits in hald (2 daughter cells, spend time getting organized, then becom working cells)
number of cell produce = to number of cell die, will get signal/growth factor (from nearby tissue/far away) , only stable cells affected by signal.
cyclins make sure cell has everything it needs
protiens, dna rep correct (if not do aptosis), measure whether cell is large enough to divid
Normal cells mature and work
go to work once stable, stop reporducng
Neoplasia
cell proliferation: process cell division, mech replace cell
cell differentiation: process specialization, cell acquire structure and function
cacer caused by abnormality in these
CAtegories cell types
undifferentiated (stem), when divide produce progenitro cell (mkae more)
poorly differentiated cells (parent/progenitor cell) divide as needed to be working cell in future
well differentiated (neurons/thyroid)
working cells
proliferation (orderly cell replacement)
stem cell divided one daughter and one progenitor, duaghter cells become more differentiated as divide until working cell
differentiation: less specialized cell develop to aquire more specialized form and funciton
getting ready to work
bone marrow, make something thatmay be lymphocyte in the future, become more specialized as continueto divide
Oncogenesis
normal cell to cancer cell
2 gene mutation
proto oncogene: normal gene control normal cell division
mutaton turn to oncogene, unlimited/abnormal division
act abnormally, make abnormal protiens, make too uch/little of protien, not packaged properly/delivered
tumor supressor genes can come and fix this, if it mutates as well is also oncogene
tumor suppressor gene: repair gene p53
fail to kill off nd adamaged cells
intiation: mutation
promotion: divide
progression: tumor cell compete and make more mutatiom and more aggressive
Characteristics cancer cells
will proliferate to form new tissue, just keep dividing and drainign resources, dont mature normally, differentiste, do job, will do too much or abnormal or too little of the tissue, missing out on fucntion
dont die off, no death of cell, immortal,
extend tissue boundaries, invade nearby tissue
metastasis
cells break off, get into blood, go downstream, metastisize/move/spread,
once grow will change rgan fucntion (take up resources, space, damage, failure)
suprress veins and nerves, cause pain and lack of bloodflow
people lose weight, muscle waste, anemia, fatigue
Generalized Effects of Cancer
cancer cachexia syndrome
wasting, weight loss, muscle waste, weakeness, anorexia, anemia
Why?
sometimes just genetic, hereditaty
horomones
carconogens/radiation
oncogenic viruses
immunologic mechanisms
NKC declien with age
Neplasia Terminology
tumor: swelling/inflammation, cellular overgorwth
benign: well differentiated/contained
crowd other tissue, take resources
malignant tumor: undifferentiated cells/not contained
spread/metastisis
take resources
Any cell can mutate
but differentiated working cell mutate, form bening/working tumor
undifferentiated rapidly divide, form malignant tumor
beningn tumor
contain tissue look like nromal tissie
may perform normal fucntion of the tissue (secrete horomone, may over secretion, or secrete wrong/not effective)
no capusle around them, do not invade neighbor tissue, but damage organ by compressing/crowding
Malignant Tumor
retake these
Cells of innate immunity
present at birth,
cells of innate imunity
macrohages; fixed/migrate
release cytokines
start healing process
dnedritic cells: antigne presenting cell
Natura KIller cell
indiff lymphocytes
Complement
seies 20 plasma protiens, enhance immune/inflamm functions
opsonization (coat bacteria as invador)
chemotaxis (cytokines to attract immune/inflamm cells)
cell mem attack complex (final event in complete cascade)
poke holes
Adaptive/Aquired Immmunity
specific cell attack specific antigen after exposure
humoral (antigen/antibody)
b cell become plasma cell
cell mediated
t cell program to attack specific antigen
active v passive
active: body make anitbodies against think you are exposed to, will make antbody again if needed
passive: given antibodies from someone else/somtjing else
antibody can be transmittes from mother to baby
Lymphocytem Development
aquired immune cells
stem cells→ b cell mature in bone marrow→t cells mature in the thymus→ move to lymph nodes to wait for antigen-presenting cell to activate
T lymphocytes
t helper cells/telesytotoxic cell
CD4?CD8
cd4
master of rugulator of innue systme
cd8
cd8 recpetior qttach to marked to invadors, kill inflectios
Anitgen Presenitng Cell
tell immune system what to attack
macrphages, dendritic cells, food,
CD4: Helpter I clellls
release cytokines
messengers, control both types of immune system
inate: activated neutrophil, macrohages, NKS,
Aquired
cause B cell to become plasma/memory
call CD8s to kill invadors
inflammatory mediators, WBC growth. factor
B lympocytes: activated by cdt 4
activated? memory b cell continue moniter for antigen
plasma cell create antobody that attach to the antigen to mark/destroy it
Antigen Epitope Antibody
antbody created to match identifying charac on antigen cell mem, called epitopes
Antibody/Immunoglobulins
no mem each, be aware that this is what we use to protect cell
Primary Immune Response
macrophage engulf antigen→presnt to cd4 cell→activate b cell→ b cell make antobody→ plasma antobody level rise w/in 3 2weeks→ vaccination produces primary immune response
Secodnary Immune System
b mem cells repsond to antigen immediatly ( no cd4 effect)
plasma antobody levels rise w/in days, booster shots
Alterations in the Immune Response
Immune Disorders
Primary
result genetic issue
genetic defect of b or t cell action
secondary
develop later in life in repsonse to another disease process
hodgkins/viral infections
Hypersensitivity
excessive/innapprop. activation of the immune response
body damaged by repsonse, not antigen
Type 1 hypersensitivty
allergic rxn , anaphalactic response/local
aquired/genetc
annoying rhinitis
debilitatinf bronchial asthma
life threatening anaphyplaxis
normally when exposed to antigen ex pollen, make antibodies against that thing
antobody hook up to mast cells ,responsible for keeping saf e from nonliving things
when mast cell sees allergen again will degranulate and dump out contents and fight
small and usual and needed, release histamine
really excessive response
Mast cell degranulation
when dump out have histamine, abnormally high amounts of hsitamine
vasodilation, bronchocontriction, vascular permeability
capillary (1 cell thick), histamine causes vessel to get bigger, cells move away from one another, whatever in capillary dump out into tissue (edema)
shortness of breath, edema, angioedema, constircts airway (swelling), itching, mucus production
hypersensitivity rxn is 2 step process
initial release of histamine and others
when all of those mast cells break down, all of those cells are open, cell membranes laying around have to clean
body break them down, when break down cell emmbranes have arachidonic acid (prostoglandins, thromboxane, leukotriene)
causes more vasodilation, pain, clotting, respiratory issues
type 1 sensitivity is double whammy
Anaphyplaxix life threatening type 1
systmeic repsonse to inflammatory mediator released in type 1 hypersensitivity, vasodilation all over, BP low
bronchoconstriction, cant breath, shortness of breath, low blood oxygenation level
epi cause increase in hr, increase in bp, open up airways
Autoimmune diseases type II,III, iV
failure to recognize self (MHCI)
immune system attacks and destorys body tissues
anti tissue antibodies appear in blood
ex. anti thyroid antibdies
Major Histocompatibility Complex (MHC)
sefl identifier foundon all cells, autoimmune, mhci is defective
Type II hypersensitivity
antibody mediated hypersensitivity
create antibodies against self cell/self receptor
block normal function
myasthenia gravis antibodies against nm receptors, neruomuscular activate muscle antibodies block muscle movement, muscle meakness
Type II hypersensitivity
Accumulation of antigen antibody complexes in blood vessels and tissues, fail to be cleared
tissue damage→ inflammation
systmeic lupus erythematosus
SLE
rheumatoid arthritis
immune complexes deposited in tissue and activate inflammation, tissue is damaged
Type IV hypersinsitivity
delayed
t cells, mean to be alerted to specific antigens, abnormal sensitized t cells attack tissue
often occur after viral illness
like cell mediated but t cells (not b cells) are activated to attack normal tissue
allergic contact dermatitis
latex/poison ivy
usually delayed, take time to develop
Treatment for Autoimmune
treat the symptom not the cause
antiinflammatory drug
cause gastrointesinal upset and bleeding
immunosuppression
leave patient vulnerable to infection, changes in metabolic function
steroids, cortisol/cortisone/prednisone, slow down immune system and syptoms get better, dont want to do for very long
in catabolic state, metabolis dont function properly, calcium problems
Human Immunodeficiency Virus
transmitted body fluids
sexual contact (fluids
breast milk
blood to blood contact
transfusions/transplant
during pregnancy/birth
contaminated needles
HIV infects a cell
virus attaches to cd4 receptors on t cell and enter cell, cd4 master controller of immune response
take out master controller fo immune system, make copies of itself
reverse transcriptase convert rna to dna, dna produce new virons, virons released
HIV diagnosis
seroconverson
immune system repsonds and antibodies against HIV appear (1-6) months
elisa
enzye linked immunosorbent assay, detects antbodies, not definitive
western blot
highly specific
cours eof HIV infection
primary infection phase
signs of sytmeic infeciton
fever, sore throat, myalgias, gi problem
within 4 weeks, last 7-10 dyas
less time to mutate, less long living virus
diagnosis at this time
reduces number of long living infected cells, maintains homogenous viral population
latent period
virus replicating, cd4 cell count falls
may last 10-11 years or longer
overt aids
cd4 count less than 200 cells per meruculiter
or aids defining illness
Aids Defining Illnesses
opportuistic infections
repsiraotry pneumocytisis carinii
gastrointestinal cryptosporidiosis
salmonella
nervous system cytomegalovirus
aids dementia complex
malignancies kaposi sarcoma, lyphoma
wasting syndrome
10% of baseline body weight with diarrhea
Managing Aids
viral load (plasma HIV RNA)
number of viruses/ml keep below 5000
more than 5000 sympton anti viral treatment
cd4 t cell counts keep above 500 ul
less than 200 ul severe symptoms
begin treatment for opportunistic infections
self management
complex treatment many dugs several times/day
adverse effects of drugs and drug interactions
cost
Inflammation and Tissue Repair
too much inflammation is bad, last step in process is tissue repair
inflammation
coordinated response to injury, reaction popportional to size of injury
purpose is to protect, keep injury in one place and prevent spread
call body defense and start healing
two types inflammation
acute inflammation: happen rapidly, work fast over few hours/days
chronic inflammation: occur when inflammatory repsonse persist, inhibit healing, cause continual cell damage and organ dysfunction
Tissue Injury
any time there is tissue injury, tissue will release chem called inflammatory mediators
begin/control/end inflammatory rpocess, in control of bdy response to injury and lead itno healing process
Acute Inflammatory Process
stages overlap
1. vasodilation
vascular permeability: capillary is vessel 1 cell thick, when dilate, cells of wall pull away from one another, fluid and particles in blood can leave vessel and go into tissue
2. cellular chemotaxis
3. systemic repsonses
Vasoldilation/Vascular Permeability
inflammatory mediator, vessel dilation and permability
resources come into area as result (fluid, bwc, platelets, plasma protien) (interstitial space)
cause tissue to swell (edema)
Acute inflammation
increased hydrostatic pressure in the vessel
hydrostatic pressure is pressure fluid exert against walls of container
in vascular space where blood is, fluid pushing against walls (blood pressure)
decreased colloid osmotic pressure in the vessel
particle pull water towards them, inflammatory mediators have opened wall, water coming out with particles, particle pull decrease
Edematous Fluid
when fluids move into tissue, called exudate
pureulent exudate rich in rpotien from wbc, microbrial organisms, and cellular debris
pus
serous/transudate
little protien mainy water filtrate of blood (fluid in blister)
It starts with
tissue damage→ inflammatory mediator→ vasoactive and chemotactic factors→ pain, heat, redness, swelling
cardinal signs of inflammation
loss of function follows
stage 2 cellular chemotaxis
cellular chemotaxis, when wbc move into area (neutrophils), call for help, send out for cytokines (chemotaxis), bring wbc to area destory infective agent, remove damgae cells, release more inflammatory meidators
stage 3 sstemic response
inflammatory meidators in blood
inflammaotyr mediatros go out to world, liver and brain bring about systemic responses
Inflammatory Substances
w/in body
inflammatory mediator: vasoldilation and vascular permeability.
TNFa IL
histamine (vasodilation) protoglandins, leukotrines
interleuken, (ILs) histamine (invoved ateriolar vasodilatio, bhronocontriction
protaglandins, pyrogen, veasodilaton, permability pain
Systemic repsonse
inflammaotry mediators, thermo regulatory cneter →
fvere
liver c reaction protien (CARP), increased bincrease (CRP)
inflammatory marlet supports immun fucntion like compliment
WHite blood cell differential
bands = mormal, wbc,
Fever
microbes, bacterial prpdicts, cyokines act aspyrogens (substace cause feb
pyrogens active protoglands to reset hypothalamic temp, eg, club
Fever the chill
pyrogenic comound i brain, raise set pt for thermostate in hpo→ body thin too cold , hear production
shivering/vasoconstriction
Fever the heat
temp riases to new set point
body thinks its war enough→ warm enough→ begin to lower temperature → sweating, wasolailation
Healing
body looking better, after trying to fight off antigen
macrpophage activate
need lots of resource,s lots can interfere
nutrition and oxygen, good circulation, immune system
anything else (heart oniter, obesity, lupu
put patient in best possible location to hkl
Tissue healing
1st intention healing, heal from inside
2nd tissue intention
1. inflammatory process
2. proliferative phase
3. fibroblast synthesize and secret collagen
growth factors: angiogenesis and epithilial cell proliferation
Proliferation: granualtion tissue connective tissue and microscopic blood vesels highly vascular cobblestone like
hyper granulation ove the edge
Contraction Remodelling
collangenase: reducse size of scar
fibroplasts: rpoduce more collagen to increase strength
Complictons of Wound Healing
Keloid: hyperplasia of scar tissue
contractures: inflexible shrinkage of tissue
dehiscence: opening of wound suture line
evisceration: opening would with extrusion of tissue and organs
stricture: narrowing of a tubular body passage from formation of scar tissue
fistula: abnormal connection between two epithilium or vessels
adhesions: internal scar tissue between tissues or organs
Patient with tuberculosis
fever, productiove cough, bloody sputum
pyrogens cause fever
in SOB lung consolidated with fibrous protiene exhausted
multi drug therapy, thoyght he was cured
three years later, x ray shows nodules in lungs told he had TB bacteria
healing takes place in place of chronic inflammation= scar tissue
Systemic Inflammatory Response Syndrome (SIRS)
inflammatory mediators travel everywhere after you dont get better
something bad has happened, inflammatory rpocess came and stayed
infection (bacteremia, fungemia, parasitemia, verimia) → sepsis→sirs
inflammaotry repsonse goes systemic
vasodilation everywhere, fluid goes everywhere out into tissue (maldistribution)
body knows something bad is happening, so chronic activation of inflammation mechanism
lead to hypermetablims and depletion of resources
not getting more resources
clinical manefestations
look at temperature (pyrogens)
heart rate 90< (what is effecting it)
measuring carbon dioxide in the blood
respiratory rate (>20)
wbc count, too low or too high is bad
bands greater than 10?
systemic manifestations
mediators of inflammation (fluid shift, hypoxemia, edema)
brain: fever, fatigue, malaise, appetite suppression, sleepiness, shivering
marrow: wbc, bands
muscles: catabolism to provide amino acids
aches pains and fatigue (cortisol)
liver: c reactive protien inflammatory marker
prodromal of worsening condition
Types of shock
3 types, caused by different things
distributive shock: poor perfusion because of capillary incompetence ( no 02 bc inflammatory mediators)
cardiogenic shock: poor perusion because of myocardial incompetence (heart not pumping blood)
hypovolemic shock: poor perfusion because of blood volume loss
Distributive shock
adequate perfusion depends on balance among: curculatinf blood volume, pumping ability of heart, size of vascular space (tone and adequacy of microcirulation)
Septic shock
bacterial endotoxin (bacteria in blood)
as bacteria die, release toxins, act as inflammatory mediators
vasodilation, increased capillary permeability
Anaphylactic shock
mast cell degradation (histmaine, leukotriene kinins, prostoglandind, inflammatory mediators)
huge amount vasoldilation and increased capillary permeability
loss of circulating fluid volume
microcirculation
hypotension
edema, wet lungs (posterior base of lungs, crackles (water, wheezing means obstruction)) decreased urine output (no blood flow to kidney)
fatigue, malaise
Distributive Shock
some intial event, Stage 1: initiate stress repsonse
systemic infection/anaphylaxis
lower systemic blood pressure
MAP (mean arterial pressure) 40-60 critical hypoperfusion
MAP less than 40, minimal perfusion
aerobid to anaerobic metabolism
decreased atp production
cell swell
lactic acid
cell/dna damage
inflammation prolonged
Stage 2: Compensatory phase
warm shock
compensatory mechanisms attempt to maintain adequate blood flow
sympathetic ns response
increase hr and bp
activation raa
vasoconstriction and decreased urine output
adh
reabsorb h20 and sodium
cortisol
catabolic - increase blood glucose - direct repsurces at immediatie problem
compensetory mech: higher circulatinf volume, higher venous return, higher co and bp
goal is to return perfusion and cellular oxygenation to normal levels
Stage 3: progressive phase (cold shock)
failure of compensatory mechanisms
aggressive intervention, vasoconstricting medications
fluid resuscitation - crystalloid/colloid
decrease 02 use/increase 02 delivery
induced coma
nutritional support
tube down throat
antibiotics (septic shock)
Stage 4: refractory shock
if imbalance of 02 supply and demand wosens
cellular 02 debt increases
progression to refractory shock state
recovery not possible
More bad news
multiple organ disfuntion syndrome
acute renal failure, acute repiratory distress syndrome (ARDS), dissmeniated intravascular coagulation (DIC)
DIC
big area of tissue die
removal of underlying cause
supportive therapy,
replacing clotting factors (FFP)
can increase clotting
anti-fibrinolytics
can increase bleeding\
Oxygen Transport
rbc born in bine marrow, not differentiated yet
have all the organelles
as grow produce hmolgobin, have large endoplastic reticulum(make protiens) (synthesizing), small golgi bodies (packaging)
when mature they lose their endoplasmic reticulum (make protien), lose their mitochondria (make atp), lose lysosome
rbs have boconcave shape, large surface area carry/exchange oxygen
made up of spectrin (internal structure), allow flexibility in capillaries
inside have hemoglobin (carry o2)
2 alpha chanin, two beta chain
each protien chain have 1 iron containing heme group
02 bind to heme grouo
erythropoieses
proccess make rbc
redcreased blood oxygen→tissue hypoxia→ kidney secrete erythropoetin (hormone)→ bone marrow stimulated→ create new rbc
red blood cells
in adults this process occur in sternum, vertebrae, ribs, and pelvis
immature rbc (nucleated
reticulocytes (rbc w/ endoplasmic reticulum)
bone marrow creare new rbc, may release, mature rbs
live for ab 120 days, membrane weakened, no nuclei, can not make new membrane components
eventually rbc break as they squeeze through the capillaries
most rbc processed in spleen, wbc in spleen proccess rbc (junk/trashed) create unconjugated bilirubin (broken down hemoglobin)
is toxic to patient, liver mus process
connect to gluconoride, excrete in bile
if liver isnt workinf right or abnormally large number rbc, have bilirubenemia
jaundice (bilirubiniemia lodge in skin)
look for in whites of eyes, mucous mem, nails
caused by liver failure or hemolysis
RBC lab values
cell count
prcnt reticulocyte
rate production
hgb/hct
hemoglobin/hematocrit count
mean corpuscular volume
mcv (size rbc)
mean corp Hgb concentration
amount hgm in each cell, color (chromic)
anemia
classified by: size (micro/macro cytic)
color (normo/hypochromic
Hematorcit
centrifuge, make rbc settle at bottom, wbc at top
normal v anemia v polycthemia
Causes Anemia
low rbc count
nutritional problems
deficient rbc production
blood loss/destruction
nutritional problems:
iron deficiency anemia
dietary deficiency
vitamin b12/folic acid deficiency
need for rbc production
intrinsic factor from parietal cell of stomch (absorb b12)
malabsorption
surgical problem, dietary (ETOH, alcohol, hard on parietal cells), neoplasm, inflammation, infection, acid blocking drugs
replace iv better than po
neurological defects
Iron deficiency Anemia
hypochromic and microctic erythrocytes
poikilocytosis (irregular shape)
anisocytosis (irregular size)
Pernicious anemia
parital cells secrete hcl and intrinisic factor
without, no b12 absorption
antiacid drugs
prilosec/pepcid
alcohol, bypass surgery
megablastic anemia
erythrocytes are large w oval shape
poikolycytosis and teardrop shape
neutrophils are hypersegmented
Deficient RBC production
aplastic anemia
abnormal stem cell
fatty replacement of bone marroq
radiation, chemical, toxins
bone marrow toxin
chronic disease anemia (most common)
chronic inflammation, lack of resources
chronic renal failure
weakness, no o2 to make atp bc no xygen in blood
angina
pallor (no hemoglobin)
sweating
tachydardia
confusion
Blood loss anemia
bled, internal or external
hemolysis
excessive detruction rbc
hemolytic anemias
making rbc but they keep degenerating, hemoglobemia, o2 low
aquired hemolytic anemias
drugs, toxins, idiopathic
atibodies from the mother (hmeolytic disease of the newborn)
hemoglobinopathies
sickle cell disease
hemolysis and vessel occulsion
thalassema (mediterranean)
defect of a/b chain in hgb
Sickle cell
mutation on beta chain of hemoglobin
when hemoglobin deoxygenated, beta chain link together form long protien rods (sickle)
tissue ischema begin cycle again
treat w/ geneic therapy
occlude vessles, clots, adhere to vessel walls (tissue hypoxia), the worse it gets the worse it gets
problems caused
sickle cells block capilaries
acute pain, infarctions (large area nectrotic tissue )
damage liver, spleen, heart, kidney, eyes, bones
pulmonary infarction→ acute chest syndrome
cerebral infarction→ stroke
sickle cells more likely to be destroyed
jaundice
Interventions for cickle cell
avoid hot/cold, strenuous exercise
keep weel hydrated, balance diet, avoid tigt clothing
look at concept map
ABO blood groups
antigen (rbc), antibody (plasma)
type a: antibodies against b/ab, can have a or o
type b: cnat have a/ab, can have b/o
type AB: can have any type of blood, universla recipient
type o: only have o blood, is universal donor
Rh factor
express the d natigen positive
no expression d, negative
rh- mom/rh+baby
mom develop antibodies to rh+ blood,
eryhtroblastosis fetalis
fetus dies bc antibodies attach baby
rhogam anti- antibody for mom
Disorders of White Blood Cells
Abnormal wbc production
leukocytosis: increase wbc
leukopenia: decrease in wbc
neutropenia: low wbc count
agranulocytosis (neutrophils)
aplastic anemia
all bone marrow cells
Etiology and Treatment wbc production disorders
etiology: infection, chemo drugs, radiation, splenomegaly ( decrease in circulate rbc, wbc, platelt), antibiotics, antipsychotic agents, genetics
treatment: underlying problem, hemapoietic drugs
force bone marrow make moe wbc, human granulocte colony stimulating factor
filgrastim/neupogen (neulasta)
Neoplasti disorder of blood cells
cancer of blood, 2 mutation
lymphoma or leukema
Leukemia v lymphoma
where it happens
leukemia: wbc formed and differentiate in bone marrow, where mutation occurs (undifferentiated)
neoplasms arising here cause leukemia or plasma cell dyscrasias
malignant
lymphoma: wbs mature and travel to lymphodi organs to mature/develop, if mutation happen here, lymphoma
neoplasms arising here are lymphomas
benign
Lymphomas
hodgkins lymphoma (after left bone marrow, in spleen)
reed sternberg cells (malignant b cells)
are much bigger, rapidly divide, take up space/resources
50 prcnt have ebstein barr virus in rs cells (closely associated)
arise in single node, grow fast and spread quickly
progressuve inavsion lymphoid tissue, eeventual inavsion all tissue
chemotherapy and radiation
non hodgkin lymphoma
associated w virus, immonusuppress, epstein bar visu, h pylori
b t nk cell
proliferation of abnormal cells
arise in lymph tissue, more common and aggressive
chemotherapy and radiation
good response to treatment bc high growth rate
Leukemia
in bone marrow, affect all cells in bone marrow (wbc, rbs, platelepts)
disruption of genes that control normal bc development
egentic and environmental factors
can occur as result of chemotharapy (bc dna damage)
diffuse replacement of bone marrow w/ unregulated proliferate, abnormal cells
fatigue, weight loss, nose bleeds, pallor, bone pain, infections
Leukema
acute: abnormal proliferation of immature blast cells
chronic: abnormal proliferation of better defined cells
myelogenous: myeloif stem cells, granulocyte, erthyrocyte and throbocyte
lymphocytic: immature lymphocytes
Leukemia affect bone marrow
bone pain, risk fracture/break
anemia (low rbc count, bc undifferentiated blood cells mutate, not producing correctly, bone marrow not making good rbc)
thrombocytopenia: bone marrow not maing platelets
immune suppression: abnormal wbc
abnormal wbc
release inflammatory mediators
tnfa and interleukin
increase capillary perm
infiltrate peripheral lymphoid organs
leave bone marrow
increase blood viscosity
too many blood cells
cause clotting
create waste products
cells break down, dump trash into gen circulation, build up
CHild w/ leukemia
fever/night sweats (inflammatory meidators)
appear pale/weak/fatigue (anemia)
cervical lymph node are inlarged (abnormal wbc infiltrate )
develop nosebleed (thrombocytopneia)
after chemotherapy develop hyperkalmia ( high level potassium in blood)
Alterations in Hemostasis
hemostasis
stopping abnormal blood flow, bllood in veins
normal:
coagulaion seal broken blood vessels
abnormal:
clotting abnorma, insifficietn
platelets aggregation
coagulation cascade
Platelets (thromobcyte)
thrombopoietin stim porduction
liver, kidney, smooth muscle, bone amrrow
megakaryocyte
form in bone marrow, break apart to form many platelt
platelt live for ab 8-9 days in circulation
store in spleen, release when need
Coagulation Factors
plasma protiens
synth by liver
von willebrand factor made by endothelium
roman numeral factors
produce the coagulation cascade
calcium (facotr IV)
essential in ann but 2 step
vitamin k
interact w/ protien for clotting factors
vessel injury and tissue injury
this is what happen coagulation
vessel injury, spasm, keep blood in vessel
cytokines are relased, inflammation, call platekets, paltelet activatign factor, platelet plug
plug in hole so stop bleed, chance to heal
platelet plug (vwf, factor vii)
bleeding stop coagulation cascade start
at end of process fibrinogen (protien produce by liver to form blood clot) gets switched and turned into fibrin, make clot overtop paltelt plug
fibrin gather like web, sew together
firbin cover up hole
healing process, fill in fibrin, clean it up, clot is still here
tissue will retract as finish up healing, if hapen quiclly cot will pop off
it will go down, reach vessel smaller than itself and stop blood flow
stop from happeneing by brekaing down clot very slowly
plasminogen trun into plasmin, goes to clots, break down itno peices, easily released, no clots back into plasma
Hypercoagulabilty (patient immobile)
increases platelet funciton
happen with many disease process (diabetes, hyperlipidemia, smoking dm,atherroscloerosis)
clotting activity
peganacy, oral contraceptivem immobility, post op, chif, malignancy
Platelt disorders
thrombocytosis (too many)
thrombocytompenia (too few)
few cause spontanues bleeding
decreased production
increased destruction/sequestrion
platelts used up in forminc clots
impaired platelt function
adp, txa, collagen etc
ITP
immune thrombocytopenia
auto immune destruciton of plateletls
kids recover adults chronic
bruising/bleeding, seteroid /immune suppressants
HIT
heparin induced thrombocytopeia
drug stop clotting from happening
used to be used indiscriminatley, doesnt stop site from clotting off, causes type 2 hypersensitivity
dont destroy, activate, little clots everywhere
autoimue formation of anitbody that activate platelet result in thrombosis
5-7% of people who get heperain get issue, 1-5% fatal
purple toe disease
How does each cause bleeding
aplatic anemia
bleed bc low platelet
splenomegaly
all platelets in spleen
ITP (idiopathic thrombocytopenia purura)
platelt destroy
liver disease
plasma protien make up platelet cascade, come from liver
vitmain k deficiency
factor for coagulation