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Path Block 11
KYCOM Block 11
455
Pathology
Graduate
11/11/2013

Additional Pathology Flashcards

 


 

Cards

Term
define emboli
Definition
occlusion or obstruction of mass transported in circulation
detached intravascular soild or gas
Term
what are 5 common sites of emboli origin
Definition
systemic vein or right heart
left heart of main artery
mesenteric/portal vein
crossed embolism
retrograde embolism
Term
what is the usually route of an arterial emboli
Definition
systemic
Term
what is the usually route of an venous emboli
Definition
pulmonary
Term
what is the usually route of an portal vein emboli
Definition
hepatic emboli
Term
what is the usually route of an paradoxial emboli (crossed emboli)
Definition
passes through ASD or VSD and into general circulation
Term
what are the 9 causes of emboli
Definition
thromboembolis
fat droplets
nitrogen or air bubbles
amniotic fluid
cholesterol (athlerosclerotic)
endocarditis vegitations
tumor
bone marrow
foreign body (bullet)
Term
what are the two types of thromboemboli
Definition
pulmonary/deep vein thrombosis

systemic/arterial
Term
what is the number one cause of pulmonary emboli
Definition
deep leg vein origion from bed rest or trauma
Term
what is the MOA of the damage of a pulmonary emboli
Definition
prevents blood from going into the lungs
Term
what are some of the complications of a small pulmonary emboli
Definition
could lodge in branching arterioles of pulmonary artery
asymptomatic if not occlusive but could lead to pulmonary hypertension in the future
Term
what are some of the complications of a large pulmonary emboli
Definition
could occlude main pulmonary artery (saddle emboli) causing sudden death
Term
define systemic emboli
Definition
emboli traveling in the arterial circulation
Term
what are the causes of systemic emboli (5)
Definition
intracardiac mural thrombi (80%)
left atrium dilation or fibrillation
heart valve vegetations
aortic mural thrombi
ulcerated atherosclerotic plaques
Term
where is an athlerosclerotic plaque most likley to form
Definition
bifurcations
Term
where are the most common sites of systemic embloli
Definition
lower extremities 75%
brain, intestine, kidney, spleen
Term
what is the cause of a fat droplet emboli (3)
Definition
fracture of long bone
trauma of soft tissue
liver with fatty changes
Term
what are the consequences of a large fat droplet emboli
Definition
occluding branching arterioles of pulmonary artery
Term
what are the consequences of a small fat droplet emboli
Definition
pass through pulmonary circulation to left heart and cause emboli in brain
Term
what are the signs of a fat droplet emboli(6)
Definition
90% asymptomatic
can be fatal
neurological
anemia
thrombocytopenia
petechial rash
Term
how big does a gas emboli need to be to cause obstruction
Definition
>100mL
Term
what are three causes of gas emboli
Definition
obstretic surgery
chest wall surgery
decompression sickness
Term
explain why decompression sickness causes emboli
Definition
sudden change in atmospheric pressure causes high pressure air to be inhaled increasing nitrogen in the blood and if the diver ascends too rapidly and depressurized nitrogen expands in the tissues and bubbles out of solution it can make a gas emboli
Term
how does amniotic fluid cause an emboli (2)
Definition
tear in placenta, rupture in uterine vein
allows amniotic fluid into maternal circulation
Term
what are 6 signs of a amniotic fluid emboli
Definition
dyspenia
cyanosis
DIC
shock
seizure
coma
Term
what do the consequences of an emboli depend on (3)
Definition
contralateral vascular supply to the tissue
tissue vulnerability to ischemia
diameter or caliver of occlusion
Term
what are common outcomes of few small emboli (2)
Definition
asymptomatic or could cause infarction
Term
what are common consequences of many small emboli (2)
Definition
decrease in volume of pulmonary circulation
pulmonary hypertension
right ventricle failure
Term
what are the common cosequences of a medium emboli (2)
Definition
hemorrhage
infarction
Term
what are the common consequences of a large emboli (2)
Definition
sudden death
saddle emboli
Term
define infarction
Definition
ischemic necrosis due to itssue anoxia
Term
what are the layers of an infarct
Definition
infarcted center
hemorrhagic line
normal tissue
Term
what are 4 common cause of infarction
Definition
occlusion or artery or venous drainage
MI
cerebral infarct: stroke
twisting of vessel
Term
what are two examples of twisting of a vessel causing infarct
Definition
ovarian torsion
testicular torsion
Term
why is a venous infarct not as terrible as an arterial
Definition
tend to cause congestion and get bypassed
Term
what are the two kinds of infarct
Definition
white - ischemic
red - hemorrhagic
Term
what is the cause of an ischemic infarct
Definition
arterial occlusion
Term
what is the cause of a hemorrhagic infarct
Definition
venous occlusion causes congestion
Term
where does a red infarct often occur
Definition
tissues with dual blood supply: lungs, SI, liver
Term
where does a white infarct often occur
Definition
solid compact organs with little collateral circulation: spleen, kidney, heart, brain
Term
what happens in the brain if it has an infarct
Definition
liquified necrosis
Term
how can a white infarct be identified
Definition
pale, dry, wedge or conical
necrotic lesion
Term
what natural mechanisms can lessen the severity of an emboli
Definition
if the tissue has dual blood supply or collateral vessels

if the occlusion is slow the body can reorganize and make collateral circulation

some cells are more resistant to hypoxia (some aernt...)

good outcome if there hasnt been ischemia or cyanosis. tissue can bounce back
Term
what tissues have low tolerance for hypoxia, how long until damage starts (5)
Definition
neurons 3-4 min
myocardial cells 20-30 min
fibroblasts, seletal muscle: hours
Term
what are the two general requirements healthy tissues need
Definition
intact circulation
normal fluid homeostasis
Term
what are what components of fluid homeostasis
Definition
BV (60% water)
BP
vessels in tact
osmolarity/protein levels
clot formation and prevention
Term
what is the general MOA of fluid balance
Definition
fluid moving out of vessel is nearly balanced by fluid coming in normally (some goes into lymphatics)
vascular hydrostatic pressure pushes fluid out and plasma colloid osmotic pressure pulls fluid in
Term
what are the two types of edema fluid and a aka for each
Definition
transudate - hydrostatic
exudate - inflammatory
Term
what dinstinguishes transudate and exudate
Definition
transudate: protein poor SG <1.012
exudate: potein rich SG >1.020
Term
what are the types of edema (4)
Definition
hydrothorax
hydroperitoneum (acetes)
hydroperocardium
anasarca
Term
what is anasarca
Definition
severe edema with subcutaneous swelling
Term
what are the 4 main causes of edema
Definition
increased hydrostatic pressure
reduced plasma oncotic pressure
lymphatic obstruction
water and Na retension
Term
what are 3 causes of increased hydrostatic pressure
Definition
impaired venous return
increased arteriolar dilation
congestive heart failure
Term
what are the two types of edema caused by impaired venous return, what is the cause of each
Definition
local: venous thrombosis in lower extremity
general: congestive heart failure
Term
what causes increased arteriolar dilation (2)
Definition
heat, neurohumoral dysregulation
Term
congestive heart failure venous effect MOA
Definition
pump fails decreasing CO and blood backs up
blood cannot leave lungs or return from body increasing venous pressure and pulmonary hydrostatic pressure
causes central venous pressure increase and systemic generalized edema
Term
congestive heart failure arterial effect MOA
Definition
pump fails decreasing CO so less blood is pumped into arteries
kidney does not see enough blood
RAAS activated: increases Na and water retension, renal vasoconstriction, ADH
congestive heart failure worsens
Term
what are two causes of reduced plasma oncotic pressure, explain each
Definition
nephritic syndrome: increased permeability of glomerular BM

reduced albumin synthesis: chirrhosis, protein malnutrition
Term
what are the two causes of lymphatic obstruction
Definition
filarias parasite wuchereria bancrofti
neoplastic lymphatic obstruction
Term
how does filarias causes edema
Definition
causes inguinal lymph and node fibrosis leading to inflammation blockage and elephantitis
Term
what are two types of neoplastic lymphatic obstructions
Definition
arm edema caused by breast cancer or radiation of axilla

peau d' orange: carcinoma of the breast obstructs superificial lymph causing edema
Term
what are the 6 locations of edema
Definition
subcutaneous
pulmonary
brain
dependent
periorbital
generalized
Term
what are 5 signs of subcutaneous edema
Definition
gross detection
dependent
pitting
impair wound healing
impair clearance of infection
Term
what are 5 signs of pulmonary edema
Definition
fluid in alveolar space
lungs 2-3x normal weight
frothy blood tinged fluid
impaired pulmonary function
impaired CO2/O2 exchange inhibits immune system
Term
what is the main cause of subuctaneous edema
Definition
heart failure
Term
what are 6 causes of pulmonary edema
Definition
left sided heart failure
congestive heart failure
adult respiratory distress syndrome
renal failure
pulmonary infection
hypersensitivity
Term
what are two types of brain edema and their causes
Definition
localized; abscess or around tumor

general: encephalitis/infection, hypertension, trauma
Term
what is a major complication of brain edema
Definition
herniation through foramen magnum causes death
Term
what is dependent edema caused by, how does it present
Definition
congestive heart failure
if standing in legs
if sitting at sacrum
Term
what is the cause of periorbital edema
Definition
initial manifestation of nephrotic syndrome
initial manifestation of general edema
Term
how does general edema present
Definition
effects body equally initially in loose CT (like periorbital)

pitting
Term
what are two causes of generalized edema
Definition
renal dysfunction
nephrotic syndrome
Term
define hyperemia
Definition
active increased inflow of blood to tisue causing redness
Term
define congestion
Definition
passive decrease outflow of blood and edema in a tissue causing cyanosis
Term
where is hyperemia located
Definition
internal (hematoma) or external
Term
what is the seriousness of hyperemia dependent on
Definition
location, size, etc
can be minimal or fatal
Term
what are 4 causes of hyperemia
Definition
trauma
athlerosclerosis
inflammation
erosion by tumor
Term
what are 4 clinical challenges with a hyperemia
Definition
<20% blood loss is ok but more can cause hypovolemic shock

trivial subcutaneous bleeding may be hiding massive brain bleed

external blood loss can cause Fe deficiency (internal Fe is salvaged)
Term
what are the 6 types of hyperemia
Definition
hematoma
petechiae
purpura
ecchymoses
hemopericardium
jaundice
Term
define hematoma
Definition
accumulation of blood in the tissue
Term
what is an example of a hematoma
Definition
dissecting aortic aneurysm casuses retropreotineal hematoma
Term
define petechiae
Definition
1-2mm hemorrhage in skin, mucous membrane, or serosa
Term
what is the cause of petechiae (2)
Definition
increased intravascular pressure, low or defective platelets
Term
define purpura
Definition
>3mm hemorrhages
Term
what are the causes of purpura
Definition
trauma and vasculitis
Term
define ecchymoses
Definition
>1-2cm subcutaneous hematoma
Term
what is the cause of ecchymoses
Definition
trauma
Term
why does ecchymoses change color
Definition
RBC are degraded by macrophages (Hb > bilirubin > hemosiderin)
Term
hemopericardium cause
Definition
crush injury ruptures myocardium or coronary A and blood traps in pericardium
Term
what is complication of hemopericardium
Definition
cardiac tamponade
Term
what causes jaundice
Definition
massive breakdown of RBC releases bilirubin
Term
what are the two sites of congestion
Definition
pulmonary and liver
Term
what are two examples of congestion
Definition
heart failure causing edema and hypoxia
Term
what are the two types of pulmonary congestion, what is the MOA of each
Definition
acute: alveolar capillary congestion causes edema and hemorrhage

chronic: like acute fibrosis
Term
what is the diagnostic sign of chronic pulmonary congestion
Definition
heart failure cells: hemosiderin laden macrophages
Term
what are the two types of congestion in the liver, what is the MOA of each
Definition
acute: congestion of central vein sinusoids
chronic: like acute with necrosis of central liver and fibrosis
Term
what are three diagnostic signs of liver congestion
Definition
nutmeg liver (necrosis)
cardiac cirrhosis
heart failure cells: hemoserdin laden macrophages
Term
what is the cut off BP for hypertension
Definition
139/89
Term
what is the diagnostic criteria for hypertension
Definition
BP of 139/89 +
taken twice and averaged
done at two office visits
Term
what are the 4 ranges of blood pressure
Definition
< 120/80 normal
120/80 - 139/89 pre-hypertension
140/90 - 159/99 stage 1 hypertension
160/100+ stage 2 hypertension
Term
why does BP have to be in a certian range, general statement of what happens if low or high
Definition
low: poor perfusion
high: vessel and organ damage
Term
what are the two causes of hypertension
Definition
systemic vascular resistance (tone) of vessels

increased CO (HR and SV)
Term
what are the three things CO (HR and SV) are dependant on
Definition
mineralcorticoids
ANP
Na
Term
where is the most impact of vascular tone occuring at
Definition
arterioles
Term
what causes changes in arteriole tone (3)
Definition
neural and hormonal regulation

local factors
a adrenergic constriction receptors
B adrenergic dilation receptors
Term
what stimulates a adrenergic receptors on arterioles
Definition
angiotensin II
catecholamines
thromboxane
leukotrienes
endothelien
Term
what stimulates B adrenergic receptors on arterioles
Definition
prostaglandins
NO
kinins
Term
what are the factors that affect local arteriole regulation
Definition
ions
pH
hypoxia
Term
what are the two general steps in the course of hypertension
Definition
asymptomatic (until too late)

symptomatic
Term
what are the complications of hypertension (15)
Definition
retinopathy
sleep apnea
kidney failure
stroke
CAD
PAD
coronary revascularization
cardiac hypertrophy (LV)
hypertensive disease (heart failure)
aortic dissection potentiation
renal failure
MI
athlerosclerosis acceleration
hayline arterolosclerosis
hyperplastic arterolosclerosis
Term
how much of the population has hypertension
Definition
25%
Term
what can increase complications of hypertension
Definition
age
african american genetics
Term
what is the prognosis of hypertension
Definition
with a decrease in BP most complications (IHD, CHF, stroke) are avoided
Term
what are the two types of presentation of hypertension, what is the percent of incidence of each
Definition
benign/idiopathic/essential (asymptomatic) 95%

accelerated/malignant (symptomatic) 5%
Term
what are some conditions that cause hypervolemia and increase CO leading to HTN (6)
Definition
renal artery stenosis
renal disease
hyperaldosteronism
hyperADH
coarctation of the aorta
pregnancy
Term
what are 3 types of conditions that cause increased CO leading to HTN
Definition
hypervolemia
stress
pheochromocytoma
Term
what occurs in pheochromocytoma
Definition
increased catecholamines
Term
what are 9 conditions causing increased vascular resistance
Definition
idiopathic/primary/essential HTN
stress
athlerosclerosis
renal artery disease
pheochromocytoma
thyroid dysfunction
diabetes
cerebral ischemia
cushings
Term
how does renal artery stenosis cause HTN
Definition
narrowing decreases blood to the kidney which causes release of renin and increase in angII

angII causes vasoconstriction increasing BP

angII activates adrenal cortex which releases ALD and increase BP

increase in BP causes HTN
Term
how does stress cause HTN
Definition
SNS activation activates adrenal medulla which releases catecholamines (E+NE)

NE increases CO and vascular resistance

both activate ang II which increases ALD (vasopressin) which increases BP
Term
how does hypertension cause sleep apnea, what are the complications
Definition
not sure

SNS acivation and stress of sleep loss lead to apenia induced hypoxia and hypercapnea
Term
how does HTN cause kidney damage
Definition
causes glomerular sclerosis which causes decreased function and evuntally disease (which causes more HTN)
Term
what is the criteria for accelerated/malignant htn
Definition
diastole >120
renal failure
retinal hemorrhage and exudates
Term
what is usually the cause of accelerated htn
Definition
extension of benign htn
Term
what are the criteria for benign htn
Definition
increased BV: decreased Na excretion, Na level alterations

increased resistance: vasoconstriction, structural defects
Term
what happens when there is increased vasoconstriction for a long time
Definition
permanent thickening of the vessel
Term
what two factors must someone have to develop htn
Definition
genetic predisposition
enivornmental factor that modifies genes
Term
hat are 5 enivornmental factors that can start htn
Definition
stress
smoking
obesity
inactivity
increased Na diet
Term
what is the tx for htn (5)
Definition
weight loss
decreased saturated and total fat
decreased Na intake
exercise
limit alcohol
Term
what are two complications htn can cause specificially in small vesses
Definition
hayline arterilisclerosis
hyperplastic arterolosclerosis
Term
define hayline arterolosclerosis
Definition
hayline wall thickening in arteriole
Term
what occurs in hyperplastic arterolosclerosis, where is the most common location
Definition
onion skining: narrowing of arterioles in concentric rings
kidney
Term
what are three causes of hyperplastic arterolosclerosis initiation
Definition
usually in malignant HTN
acute BP elevation
renal or cerebral A injury
Term
what are 5 words that describe a neoplastic cell, explain each
Definition
heritable: cused by genetic changes (parent to daughter cell not mom to baby)

clonal: come from single cell

unregulated: loss of response to growth controls

competitive: compete with normal cells for metabolites

non-autonomous: need blood, nutrients, and sometimes hormones
Term
what are 4 signs of a benign tumor
Definition
innocent microscopic characteristics: resembles tissue of origin, well differentiated

localized

growth is slow and can regress or pause

well demacrated
Term
why can a benign tumor be surgically removed
Definition
it is well demacrated
Term
what are 4 characteristics of a malignant tumor
Definition
anaplasia (most of the time)
metastasis
erratic growth
mitotic figures
Term
define anaplasia
Definition
cells without polarity organization
usually loss of differentiation
many abnormal mititoc figures
Term
define metastasis
Definition
can invade adjacent tissue and spread to distant sites in the body
Term
define dysplasia
Definition
disorderly non-neoplastic proliferation usually of epithelia
Term
what are 4 characteristics of dysplasia
Definition
loss of architectural uniformity and cell orientation
pleomorphic
hyperchromatic
carcinoma-in-situ
Term
define pleomorphic
Definition
cells vary in size and shape
Term
define hyperchromatic
Definition
deeply stained nuclei
Term
define carcinoma-in-situ
Definition
dysplasia through entire epithelial thickness but not BM (pre-invasive cancer)
Term
how is dysplasia treate
Definition
reversable if it does not involve entire epithelial thickness
Term
what are the 5 steps in tumor naming
Definition
1. suffix -oma
2. if benign skip to step 4
3. add carcin- if epithelial origin or sarc- if mesenchyma
4. choose a root to describe cell origin
5. if none of the roots fit choose hamartoma or coristoma
Term
what does -oma mean
Definition
swelling
(for neoplasms and non-neoplasms)
Term
name the root for: fibroblasts, myxoid, cartiladge, osteoblasts, fat
Definition
fibro
myxo
chondro
lipo
Term
name the root for: notochord, smooth muscle, striated muscle, perineurium, endoneurium
Definition
chordo
leiomyo
rhabdomyo
schwannao/neurolemmo
neurofibro
Term
name the root for: vessels, lymphatics, glomus, synovium, mesothelium
Definition
hemangio
lymphangio
glomangio
synovio
mesothelial
Term
name the root for: arachnoid granulations, lymphocytes, placenta, adrenal medulla,
Definition
meningio
lympho
chorio
phrochromocyto
Term
name the root for: glandular epithelium, swuamous or transitional epithelium, resemblence of embryonic cells, totipotent cells from germ layers
Definition
adeno
papillo
blasto
terato
Term
what type of root is for a tumor that has hair and teeth
Definition
terato

totipotent cells from germ layers
Term
what is a hamartoma, how can it be identified
Definition
developmental abnormality, not a tumor

contains tissue of origin but in wrong proportions and disorganized
Term
what is a choristoma (ectopia)
Definition
mass of normal tissue in abnormal location
Term
what is the qualification to be considered a carcinogenesis
Definition
must bypass hayflick limit: length of telomerase or telomerase alternative mechanism
Term
what are the two categories of causes of carcinogenesis
Definition
expansion of single progenerator with non-lethal mutation

defect in DNA repair genes are unable to fix a mutation
Term
what are the two types of single progenitor mutations
Definition
germline / inherited
somatic / acquired
Term
what is the problem in hderditary nonpolyposis colon carcinoma syndrome (NHPCC)
Definition
defect in DNA mismatch repair
Term
what is the problem in xeroderma pigmentosum
Definition
defect in nucleotide excision repair
Term
what is the problem in Bloom's, Werner's, and rothmund thomson syndromes
Definition
RecQ helicase mutations
Term
what is the problem in BRCA1/2 mutations
Definition
defect in double strand break repair cases breast cancer
Term
what are the three effects of carcinogenesis, the thee MOA categories of cancer development
Definition
activation of oncogenes (mutant alleles) transforms cells and promotes autonomous cell growth

mutation of growth inhibiting cancer supressor genes (anti-oncogenes)

mutation of genes controlling apoptosis
Term
in general, how do oncogenes cause cancer
Definition
dominant: only one needs to be activated

change gene sequence making new protein that is no longer inhibitory (oncoprotein)

product causes over production of normal proteins
Term
what is an autocrine loop
Definition
when some cancer cells acquire the ability to make the same growth factors they are responsive to so it creates loop that sitmulates the continued growth of the tumor
Term
how do anti-oncogenes work
Definition
mutation of growth inhibitng cancer supressor is recessive so both genes must be damaged
Term
what is an example of dominant mutation of genes controling apoptosis
Definition
overproduction of BCL-2 in follicular lymphoma
Term
what is an example of recessive mutation of genes controling apoptosis
Definition
homozygous loss of p53 in most cancers
Term
what is the two hit hypothesis
Definition
two mutations are needed to cause retinoblastoma (an many other cancers)

applies to all recessive cancer genes
Term
what are the two reasons cancer can divide unlimitedly
Definition
telomerase is turned on

alternative lengthening of telomeres mechanism
Term
how does the alternative lengthening of telomeres mechanism work
Definition
recombination and amplification of dna at chromosome ends
Term
what is the normal activity over time at the telomere, what is a telomere made of
Definition
repeat on end of chromosome with TTAGGG telomeres that shorten as the cell divides (unless it has telomerase like in germ or stem cells)
evuntally it will get too short and will register as DNA damage and signal apoptosis
Term
why does a tumor need to do angiogenesis, what if it doesnt
Definition
blood can only diffuse 2mm so when a big tumor grows blood cannot get to the center

some neoplasms grow so fast the interior necrosis
Term
how do tissues protect against excessive angiogenesis
Definition
tissues have anti-angiogenesis factors and angiogenesis inhibitors to keep it in check
Term
what are the ways cancer increases angiogenesis
Definition
loss of angiogenic inhibitors
production of angiogenic initiators
Term
what are the inhibitors of angiogenesis cancer turns off
Definition
p53 mutation allows for angiogenesis to start
Term
what are the angiogenic initiators cancer turns on, how are they induced
Definition
VEGF: controlled by RAS, induced by hypoxia inducible factor (HIF-1)

FGF: stored in ECM, released as tumor cleaves ECM during invasion
Term
how does angiogenesis work in benignn tumors
Definition
it dosent
the pituitary grows until it pushes on stella turcia and squishes the vessels and then it spontaneously regresses due to the nutrient limitation
Term
what are the 4 things a cancer needs to overcome to metastasise
Definition
breech BM, interstitial CT, and vessel wall
evade host immune system
Term
what are 2 ways cancer tries to evade host immune system
Definition
form emboli with platelets so they hide in cell

travel as single cell and hope to not get caught
Term
what is the most common 2 places of cancer spread
Definition
liver and lungs
Term
what are the 2 least common places for cancer spread
Definition
skeletal muscle
Term
where does a cracinoma usually spread
Definition
lymph
Term
where does a sarcoma usually spread
Definition
hematogenous
Term
where does colon carcinoma usually spread
Definition
penetrates gut wall and spreads to peritoneal cavity
Term
where does lung cancer usually spread
Definition
pleural cavity
Term
where does ovarian cancer usually spread
Definition
peritoneum
Term
what are the 4 MOA to cancer malignancy
Definition
detachment of tumor cells from eachother
attachment of tumor cells to matrix components
degredation of ECM
migration of tumor cells
Term
3 ways tumor cells detach from eachother
Definition
inactivation of E-cadherin genes (in almost all epithelial cancers)

mutation of B-catenin genes

changes in cellular adhesion molecules (CAMs) gene expression
Term
how do tumor cells attach to matrix when traveling (2)
Definition
lamanin: cancer cells have receptors on all sides (unlike normal cells)

fibronectin: cancer cells dont have it so they can detach from ecm and reattach to it later
Term
how do tumor cells degrade ECM (4 steps)
Definition
tumor secretes proteases or stimulates fibroblasts to make...

MMP (matrix metalloproteases): digest protein

cathepsin D: peptodase

type IV collagenase
Term
how do tumor cells migrade (3)
Definition
clevage produces of some ECM components are chemotactic for tumor cells

tumor cell derived cytokines (autocrine motility factor)

growth factors IGF-1 and II
Term
what are the 3 most common cancers in men
Definition
prostate
lung and bronchus
colon and rectum
Term
what are the 3 most common cancers in women
Definition
breast
lung and bronchus
colon and rectum
Term
what are the 3 most deadly cancers in men
Definition
lung and bronchys
prostate
colon and retcum
Term
what are the 3 most deadly cancers in women
Definition
lung and bronchys
breast
colon and rectum
Term
where do most cancers come from
Definition
epithelium
Term
how can mortality of cancer be determined, give two examples
Definition
more preventable = more deadly

smoking: lung cancer
western diet (low fiber, high fat): colon and rectal cancer
Term
who is cancer more common in
Definition
elderly and men
Term
what is the common cause of cancer in the young
Definition
genetic mutation
Term
what is the most common cancer in japan
Definition
stomach
Term
what is the most common cancer in us
Definition
breast
Term
what is the most common cancer in africa
Definition
hepatocellular carcinoma
Term
what is the most common cancer in KY, why
Definition
lung and bronchial
number one smoking state
Term
where does hepatocellular carcinoma come from, what cancer does it cause
Definition
aspergillus in moldy nuts and grain releases alfatoxin causing carcinogens that progresses to liver cancer
Term
what is the most potent carcinogen
Definition
alfatoxin from aspergillus
Term
what is the most common origin for cancer under 4yo
Definition
neural or hematopoetic
Term
what is the most common origin for cancer over 4yo
Definition
soft tissue
Term
how can familial cancers be identified
Definition
in 2+ close relatives
multiple or bilateral tumors
Term
what are the six causes of acquired paraneoplasitc disorders
Definition
persistent regenerative cell replication

hyperplastic and dysplastic proliferation

chronic atrophic gastritis

chronic ulcertive colitis

leukoplakia of oral cavity, uvula, or penis

vilous adenomas of the colon
Term
two examples of persisent regenerative cells replication causing cancer
Definition
squamous cell carcinoma in long unhealed wounds

hepatocellular carcinoma in cirrhotic liver
Term
two examples of hyperplastic and dysplastic prolieration causing cancer
Definition
endometrial carcinoma from hyperplasia

bronchogenic carcinoma in dysplastic bronchial mucousa of smokers
Term
one example of chronic atrophic gastritis causing cancer
Definition
gastric carcinoma in pernicious anemia
Term
example of chronic ulcerative colitis causing cancer
Definition
colorectal carcinoma
Term
example of leukplakia of oral cavity, vulva, or penis causing cancer
Definition
squamous cell carcinoma
Term
example of vilous adenoma of the colon causing cancer
Definition
high risk of transformation to colorectal carcinoma
Term
explain the normal process of regulation og G1 to S stage of the cell cycle
Definition
cyclins are transcribed from DNA and complex with CDK phosphorlyating them

complexes phosphorlyate RB protein

RB protein release E2F transcription factor

E2F promotes proteins allowing cell to go from G1 (rest) to S (prep for division)

in M phase RB is dephosphorlyated

RB binds E2F transcription factor

cell division stops in G1
Term
what three oncogene dysruptions in the cyclin cell regulation cause cancer
Definition
cyclin D over expression

CDK4 over expression

CDK inhibitor down regulation
Term
what differnt combinations of cyclins and CDK are there (4)
Definition
cyclin D with CDK4 or CDK 6

cyclin E with CDK2

cyclin A with CDK
Term
what does cyclin D overexpression cause to happen, what three cancers have this
Definition
lots of CDK4 activation

breast, liver, lymphoma
Term
what does CDK4 over expression cause to happen, that three cancers have them
Definition
lots of RB phosphorlyation

sarcoma, melanoma, glioblastoma
Term
how are CDK inhibitors rendered ineffective by oncogenes (4)
Definition
down regulation
degredation
cytoplasmic mislocation
sequesteration
Term
what occurs in a RB mutation
Definition
RB cannot be dephosphorlyated so it cannt bind E2F
Term
what are the three types of RB mutations
Definition
familial retinoblastoma
sporadic retinoblastoma
oncogenic virus retinoblastoma
Term
familial retinoblastoma: inheritence, effets (2)
Definition
autosomal recessive but looks like dominant because it is only one random mutation away from dominant

retinoblastoma and WATCH OUT FOR osteosarcoma
Term
what occurs in sporadic retinoblastoma
Definition
both normal RB genes get a somatic mutation
Term
what occurs in oncogenic virus retinoblastoma, 3 example viruses
Definition
virus binds RB so it cannot bind E2F

(polyomavrus, adenovirus, HPV)
Term
explain how normal p53 works (2 prep steps, 3 cell effects)
Definition
DNA damage signals unbinding of p53 from MDM2

p53 activates transcription factors that turn on genes to...

1. activate CDK inhibitors stopping cyclin/CDK complexes from phosphorlyating RB protein pausing the cell cycle

2. activate DNA repair

3. activate apoptosis if it is not successful
Term
what does p53 do in a successful and unsuccessful DNA repair
Definition
success: p53 promotes transcription of MDM2 which degrates p53 (short half life)

not: p53 promotes transcription of apoptosis genes (like BAX)
Term
what are three ways to have a p53 problem
Definition
Li-fraumeni syndrome - inherited
inhibited by DNA viruses
acquired- two random mutations
Term
what occurs in li-fraumeni syndrome, what is the effect
Definition
inherit 1 p53 mutation in every cell
25x chance of malignancy by 50 yo
Term
how do viruses inhibit p53, 3 example viruses
Definition
proteins of virus encode oncogenes
(HPV, HBV, EBVg7)
Term
how does TGF-B regulate cell cycle
Definition
binds receptors 1-3 and sends signal to SMAD and stimulates CDK1 which stops transcription of cyclin E and A, stopping cell in G1
Term
when is TGF-b mutated, what part of the process is normally wrong
Definition
mutated in cell cancers

usually SMAD4 or type II receptor mutation
Term
explain how cell size is regulated
Definition
B-catenin senses cells are too far away and activates growth
B-catenin binds E-catenin making intracellular adhesions when cells are closing stopping B-catenin from activating cell growth
Term
what is the role of APC, how does it work
Definition
some B-catenin will be unable to pair with C-cadherin and may still go to the nuclei and say for the cell to grow

APC comes in and complexes with TcF transcription factor in quiescent cells forming destruction complexes and degrading excess B-catenin
Term
what occurs in a homozygous APC/B-catenin mutation
Definition
loss of APC activity stops degradation of B-catenin causing trancription of cell cycle proteins and cell growth
Term
what occurs in a heterozygous APC/B-catenin mutation
Definition
familial adenomaus polyposlsosis:
adenomatus polyps form on colon in teens and 20s
some will ahve malignant transofrmation
Term
how does MYC work
Definition
cell is induced to divide so MYC binds DNA causing transcription of growth genes (like CDK)

right after delivering the message they should stop being made
Term
what happens in a oncogene induced MYC mutation
Definition
amplification of a region that contains MYC
Term
what are the 4 oncogene induced MYC mutations
Definition
MYC over expression
N-MYC over expression
L-MYC over expression
burkitt lymphoma (B cell tumor)
Term
what cancers result from MYC over expression (3)
Definition
breast, colon, lung
Term
what cancer results from N-MYC over expression, what is a microscopic sign
Definition
neuroblastoma

karotype double minutes (little MYC chromosomes with repeats)
Term
what cancer results from L-MYC over expression, what is a microscopic sign
Definition
small call cancer in the lung

karotype double minutes (little MYC chromosomes with repeats)
Term
what is the cause of burkitt lymphoma
Definition
B cell tumor due to translocation of MYC from CH8 to CH14 next to heavy chain Ig genes increasing Ig production in WBC
Term
what should a chromosome 14 issue tell you
Definition
lymphoma
Term
how does ABL work
Definition
phosphorlyates things via tyrosine kinase, sends signals to nucleus, promotes apoptosis when DNA is damaged
Term
explain how oncogenes cause ABL translocation
Definition
oncogene induces translocation of ABL from CH9 long arm to CH22. ABL is now with BCR making phildelphia chromosome. CH9 becomes abnormally long and CH22 short.
Term
what does a ABL translocation cause to happen within the cell
Definition
TK activates RAS which cannot localize to the nucleus and apoptosis stops
Term
what is a phildalphia chromosome diagnostic for
Definition
chronic myeloid leukemia
Term
what does RAS do
Definition
GF binds RAS receptor which signals cell proliferation via MAP kinase mediated transcription of cell cycle proteins

inactivated RAS is bound to GDP after ONE signal is sent
Term
what is the most common oncogene mutation, what happens
Definition
RAS mutation

GTPase activity is broken and RAS is always activated causing continous transcription of cell cycle proteins
Term
what are two categories of issues an oncogene can cause with growth factor receptors
Definition
mutant receptor proteins deliver continous mitogenic signals to cells

over expression of growth factor receptor
Term
what occurs in a mitogenic EGF receptor mutation
Definition
it is continously activated (despite absence of EGF or TGFa and more cell division occurs allowing more chance for mutations
Term
what occurs in oncogenic over expression or ERBB1 EGF, where does this happen
Definition
increased activation
squamous cell carcinoma
Term
what occurs in HER3 (ERBB2) oncogenic over expression
Definition
increased activation causes gene to be expressed over and over and so when transcription is turned on HER2 builds up on surface of cellls causing breast cancer
Term
how is apoptosis regulated and activated
Definition
BCL-2 binds BAX so cytochrome C isnt activated

BCL-2 lets go of BAX which binds BAD which activates cytochrome C which binds APAF-1 which begins capsase cascade
Term
what are three types of apoptosis mutations
Definition
BCL-2 over expression
follicular lymphoma
APAF-1 mutation
Term
what occurs in BCL-2 over expression
Definition
too much BAX is stopped so apoptosis cannot occur
Term
what occurs in follicular lymphoma
Definition
BCL-2 translocates from Ch12 to CH14 by Ig heavy cjain gene causing excessive (not rapid) proliferation
Term
what occurs in a APAF-1 mutation
Definition
loss of functional gene in some melanomas
Term
how does UV ratiation cause neoplasm
Definition
causes pyrimidne dimers in DNA mutating protoncogenes and tumor supressor genes causing skin cancer
Term
what causes ionizing radiation
Definition
X, Y, a, B rays, protins, neutrons
Term
how does ionizating radiation cause neoplasm
Definition
causes ss and ds breaks of cells, especially those in G2
Term
what is an example of RNA oncogenic virus that causes neoplasm, what kind of neoplasm
Definition
human T cell leukemia virus (HTLV-1) targets CD4 causing leukemia
Term
what are three DNA oncogenic visues and what neoplasm do they cause
Definition
hepatitis B: hepatocellular carcinoma
EBV: burkitt (B cell) lymphoma
HPV: benign squamous cell papilloma
Term
what types of HPV cause cervical cancer
Definition
16 and 18
Term
what kind of cancers are HPV very commonly involved in
Definition
75% of squamous cell carcinoma and 100% of preneoplastic disorders (dysplasia)
Term
what is HHV8
Definition
kaposki sarcoma associated herpes virus
Term
what two parts of HPV cause problems
Definition
viral proteins E6 and E7
Term
what does HPV viral protein E6 do
Definition
inhibit p53 stopping apoptosis
Term
what does HPV viral protein C7 do (3)
Definition
inhibits p53 stopping apoptosis

inhibits p21 which now can no longer inhibit cyclin D / CDK4 complex so now it can run free and cause growth

inhibits RB-E2F complex so it can cause transcription and growth
Term
what neoplasms does helobacter pylori cause
Definition
gastric carcinoma and gastric lymphoma (aka marginal lymphoma or maltoma)
Term
what is evidence that host immune defenses have a role in tumor frmation
Definition
increased risk of cancer and autoimmune disease
Term
what are the two types of tumor antigens, where are they located
Definition
on cell surface MCH-1 to be recognized by CD8

tumor specific antigens: only on tumor cells

tumor associated antigens: on tumor cell and some normal cells
Term
where are tumor specific antigens appearing (5)
Definition
oncoprotein (RAS), over expressed proteins (HER-2), oncogenic virus antigens, oncofetal proteins (CEA), a-feroprotein
Term
what are the types of tumor associated antigens
Definition
tissue specific and differentiation specific
Term
what is an example of a tumor associated antigen, what can it be used for
Definition
prostate specific antigen

not good for prostate cancer because it shows cancer, inflammation, enlargement, ejaculation, etc
Term
anything that decreases immunity....
Definition
increases risk for cancer
Term
list 4 cancer immunosurvelence mechanisms
Definition
subclones with antigens recognized by immune system are eliminated

tumor may have abnormal HLA and get destoried

tumor may not have co-stimulatory molecules for sensitization to T cells

immune supression by carcinogen or expression of FAS B tumor stimulates apoptosis of T cells
Term
what are the 4 clinical features of a neoplasm
Definition
impinge on adjacent structures

hormone production

ulceration

cancer cachexia
Term
what are two examples of a neoplasm impinging on adjacent structures
Definition
pituitary adenoma: compresses and destories gland (hypopitutiarism)

carcinoma of the bile duct: fatal biliary tract obstruction
Term
what are two examples of a neoplasm secreting hormones
Definition
adenoma in islets causes hyperinsulinism

carcinoma of adrenal cortex causes hyperaldosteronism
Term
what are 4 complications of neoplasm ulcer
Definition
bleeding
predisposition to infection
gastric ulcer can cause Fe deficient anemia
intrussuception: tumor protrudes into lumen and causes telescoping leading to infarction
Term
what are 5 signs of cancer cachexia
Definition
cancer wasting syndrome: loss of body fat and mass, weakness, anorexia, anemia

with increased metastasis comes increased cachexia
Term
what are 4 persumed causes of cancer cachexia
Definition
increased calories expended and basal metabolic rate

reduced food intake due to abnormal appetite control

protein mobilizing or lipolytic molecules released caused by tumor or host cytokines and proteolysis factor release

TNF release inhibiting appetite and lipoprotein lipase
Term
what are 5 examples of paraneoplastic syndromes
Definition
cushings syndrome
SIADG
hypercalcemia
venous thrombus
non-bacterial thrombotic endocarditis
Term
define paraneoplastic syndrome
Definition
cannot be explained by tumor tiself, its origin, or secretions
Term
what are 3 concerns with paraneoplastic syndrome
Definition
early sign of neoplasm
lethal side effects
mimic metastastic pattern
Term
what are three neoplasms that are associated with cushings synfrom and what do they secete
Definition
small cell carcinoma of lung: insulin
pancreatic carcinoma: ACTH
neural tumor
Term
what are two neoplasms that are associated with SAIDH and what do they release
Definition
small cell carcinoma of the lung: ADH, ANP

intracranial neopasm
Term
what neoplasm is hypercalcemia associated with, what does it release
Definition
small cell carcinoma of the lungs: PTH, TNFa, TNF, IL-1
Term
what two neoplasms are associated with brnous thrombosis, what do they produce, what effect does this have
Definition
pancreatic carcinoma
bronchogenic carcinoma

make mucins that cause clotting
Term
what neoplasm is non-bacterial thrombotic endocarditis associated with, what does it secrete, what is the effect
Definition
found in advanced cancer

secretes tissue factors that cause hypercoagulation
Term
what is the purpose of staging and grading
Definition
quantify agressiveness and current spread
Term
what is the purpose of grading a tumor
Definition
tells agressiveness.
differes per type of carcinoma
tells how well differentiated
Term
what are the levels of tumor grading, what do they mea
Definition
1: typical tissue - well differentiated
2: nothing like the neighboring tissue
Term
what are the two ways to stage cancer
Definition
TNM and american joint comission
Term
what does TNM stand for
Definition
primary TUMOR
regional NODE involvement
METASTIASIS
Term
what are the 5 T rankings, what do they mean
Definition
Tis: confined to epithelium (in situ)
T1: small
T2: more invasion at primary site (medium)
T3: large - invasion beyone primary site margin
T4: very large - in adjacent tissues
Term
what are the 4 N rankings, what do they mean
Definition
N0: not spread to adjacent nodes
N1: spread to regional nodes
N2: spread to many regional nodes
N3: spread to distand nodes
Term
what are the 2 M rankings, what do they mean
Definition
M0: no metastasis
M1: metastasis
Term
what TNM is stage 0
Definition
Tis N0M0
Term
what TNM is stage 1
Definition
T1 N0M0
Term
what TNM is stage 2
Definition
T3 N0M0
Term
what TNM is stage 3
Definition
any T, N > 0, M0
Term
what TNM is stage 4
Definition
any T, any N, M1
Term
what are the three categories of testing for tumors
Definition
obtaining sample
immunohistochemistry
serum tumor markers
ancillary tests
Term
what are 4 ways to obtain a tumor sample
Definition
excision
biopsy
aspiration
smear (PAP)
Term
what is the purpose of tumor immunohistochemistry
Definition
determine tissue of origin of metastic or poor differentiated tumor
Term
how does immunohistochemistry work
Definition
monoclonal antibody markers are identified
Term
what are 4 examples of monoclonial antibody markers that are identified with immunohistochemistry and their associated cancers
Definition
thyrobluboin - thyroid cancer
S100 - melanoma or neural
CD markers - lymphoma/leukemia
estrogen - breast cancer
Term
what are the uses of serum tumor markers
Definition
tumor specific or associated markers that screen, monitor Tx, or detect recourrance of tumors
Term
what are three examples of serum tumor specific markers and their associated cancers
Definition
a-fetoprotein (AFP): hepatoma, testicular germ cell tumor
B-hCG: trophoblastic tumor, carcinoma
prostatic specific antigen: prostate cancer
Term
what are 4 ancillary tests for tumors, what two are used for prognosis
Definition
flow cytometry: prognosis
PCR/dnA probes
karyotyping: prognosis
flourescent in situ hybridization (FISH)
Term
what is a proband
Definition
person you are studying in a inheritence chart
Term
whem you have anemia in an adult you should think of...? why?
Definition
GI problem because Fe deficiency in the USA is very uncommon without some GI condition
Term
what is a guaiac test
Definition
fecal occult blood screen looks for RBC exodgenous peroxidase (turns blue)
Term
what does hematochezia mean
Definition
visible blood in stool, distal GI bleed
Term
what does melena mean
Definition
tarry black stool from blood exposed to digestive enzymes
stomach or upper GI bleed
Term
what causes a false positive guaiac test
Definition
rare meat
crvicterous veggies
horseradish
myoglobin
Term
what causes false negative guaiac test
Definition
ascorbic acid (reducers)
Term
what is the problem in LeFraumini syndrome
Definition
p53 mutation
Term
sporatic colon cancer: when does it appear, now many areas affected, how do you get it, where does it go
Definition
shows in older age
1 affected spot
little family hx (20%) its spontanous
majority on left/distal colon
Term
familial adenotamous polyposus: cause, when does it appear, how many areas affected, how do you get it, where does it go
Definition
APC mutation allows B-catenin into cell to allow division
appears in 20-30s
thousands of polyps
germline mutation
majority on left/distal colon
Term
hereditary non-polypupus cancer syndrome: when does it show up, how many areas effected, how do you get it, where does it go
Definition
shows in 40s
several polyps
family history of colon cancer (1 inherited mutation increases chances of more)
appears in right/proximal colon
Term
what cancers is HMPCC associated with
Definition
endomterial and ovarian
Term
what causes HMPCC
Definition
microsatelite instability in APC gene

repetative microsatelites are subject to mismatch and when DNA replicates it slips and messes up so DNA mis match repair fixes it. but the repair gene is broken so it allows for amplication of the microsatelites

if this occurs in a coding gene (like APC) it allows for bad proteins. bad APC allows B-catenin to keep allowing cell replication
Term
how is HMPCC identified in the lab
Definition
immunohistochemistry

antibody used against genes. if they bind there gene is there and working.

varability in length of microsatelites in ANY (not just the tumor) tissue can cause mis match repair issue
Term
what does a TP53 mutation cause to happen
Definition
prevents apoptosis in all cancers
Term
how often is a RAS mutation seen
Definition
30% of all tumors
Term
explains what happens in chronic myeloid leukemia
Definition
ABL normall detects DNA damage and uses TK to phosphorlyate to cause apotosis

ABL is translocated from Ch9 to Ch22 where it fuses with BCR and activates RAS causing cell cycle protein trancription and is prevented from going to nucleucs to start apoptosis
Term
what gene mutations cause growth promotion (5)
Definition
HER2
RAS
ABL
MYC
CD/CDK4
Term
what gene mutations cause loss of tumor supression (3)
Definition
RB
TGF-B
APC
Term
what gene mutations cause stop of apoptosis (3)
Definition
TP53
BCL-2
APAF-1
Term
define shock
Definition
cardiovascular collapse
Term
5 causes of shock
Definition
hemorrhage
trauma of burns
MI
pulmonary embolism
sepsis
Term
MOA of shock
Definition
systemic hypoperfusion due to reduced CO and VO

hypotension, impaired tissue perfusion, cellular hypoxia

initially cellular injury is reversible but over time it becomes irreversible
Term
5 types of shock
Definition
cardiogenic
hypovolemic
septic
neurogenic
anaphylactic
Term
what causes cardiogenic shock
Definition
myocardiacal pump failure
Term
what are 2 examples of cardiogenic shock
Definition
MI
ventricular arrhythmia
Term
what are 5 signs of cardiogenic shock
Definition
hypotension
weak rapid pulse
cool, clammy, cyanotic
Term
what are the two areas of dysfunction in cardiogenic shock
Definition
systolic dysfunction
diastolic dysfunction
Term
what is the progression of systolic dysfunction in cardiogenic shock
Definition
ventricular ischemia, structural compormize, or dysrhythmia causes

systolic dysfunction which causes

decrease in SV which causes

decrease in CO which causes

cellular oxygen delivery decrease
Term
what is the progression of diastolic dysfunction in cardiogenic shock
Definition
decreased filling in diastole causes

pulmonary hypertension and edema which causes

decreases oxygenation of blood which causes

tissue hypoxia
Term
what is the caue of hypovolemic shock
Definition
loss of blood or plasma volume
Term
what are three examples of causes of hypovolemic shock
Definition
hemorrhage
burns
trauma
Term
what are 5 signs of hypovolemic shock
Definition
hypotension
weak rapid pulse
cool, clamy, cyanotic
Term
what is the MOA of hypovolemic shock
Definition
relative or absolute hypovolemia leads to

decreased BV, venous return, SV, CO which causes

decreased cellular oxygen delivery
Term
define septic shock
Definition
shock caused by systemic microbe infection
Term
what usually causes septic shock
Definition
gram negative endotoxin producing bacilli
Term
how do microbes cause septic shock
Definition
LPS released when cell wall is degrated from inflammatory response
Term
why is antibiotic treatment difficult in septic shock
Definition
antibiotics could make things worse initially by breaking up LPS
Term
define septic shock
Definition
shock caused by systemic microbe infection
Term
what usually causes septic shock
Definition
gram negative endotoxin producing bacilli
Term
how do microbes cause septic shock
Definition
LPS released when cell wall is degrated from inflammatory response
Term
why is antibiotic treatment difficult in septic shock
Definition
antibiotics could make things worse initially by breaking up LPS
Term
what are 6 microbes that commonly cause septic shock
Definition
E. coli
salmonella
shigella
pseudomonas
neisseria
haemophilus
Term
explain the progression of septic shock
Definition
infection > systemic inflammatory response syndrome > sepsis > severe sepsis > septic shock
Term
what are 4 signs of septic shock
Definition
skin is initially warm and flushed due to peripherial vasodilation
electrolyte imbalance
metabolic acidosis
decreased urine output
Term
what are the three main venues septic shock causes damage through
Definition
endothelial damage
release of inflammatory cytokines and acute phase reactants
CNS endocrine activation
Term
how does endothelial damage contribute to the symptoms of septic shock (3)
Definition
increased capillary permeability
microemboli
activation of the coagulation system
Term
what inflammatory cytokines cause damage iin septic shock (4)
Definition
IL1, TNF, NO, PAF
Term
what acute phase reactants cause damage in septic shock (3)
Definition
complement,
prothrombin
plasminogen
Term
how do cytokines and acute phase reactants cause problems in septic shock
Definition
myocardial depression
vasodilation/hypotension and increased permeability causes decreased contractin and CO
microemboli
Term
what CNS and neuroendocrine activation occurs in septic shock
Definition
selective vasoconstriction
hypermetabolic state that increases oxygen demand
Term
what are the overall results on the body in septic shock
Definition
combination of vasodilation and constriction
increased permeability
increased cell demand
microemboli

all lead to poor distribution of blood volume which decreases delivery of oxygen to tissues
Term
what causes neurogenic shock
Definition
anasthetic accident or spinal cord injury causes loss of vascular tone and peripherial pooling of blood
Term
what is the MOA of neurogenic shock
Definition
loss of sympathetic tone initiates parasympathetic response which decreased HR and CO

loss of sympathetic tone causes vasodilation which decreases BP, venous return, SV, CO and thus O2 delivery to tissues
Term
what causes anaphylatic shock
Definition
IgE mediated hypersensitivity causes vasodilation and increased vascular permeability
Term
what are the three stages of shock
Definition
nonprogessive
progressive
irreversible
Term
what are the activated compensatory mechanisms in the nonprogressive stage of shock
Definition
baroreceptor reflex
catecholamines
fever
sympahtetic stimulation
ADH
RAAS
Term
what does fever in the nonprogressive stage of shock lead to
Definition
increased BMR
Term
explain the sympathetic response in nonprogresive shock
Definition
anterior pituitary releases ACTH which tells adrenal cortex to release glucorticouds which increases blood sugar to meet metabolic need
Term
how is ADH activated, what does it do
Definition
low BP activates causing ADH release from pituitary which increases water reabsorption in kidney increasing BV
Term
explain the RAAS
Definition
decreased flow to kidney causes renin secretion initiating RAAS which releases angiotensin causing adrenal cortex to release aldosterone which causes reabsorption of Na and water to increase BV
Term
what is the overall affect of the compensatory mechanisms in the nonprogressive stage of shock
Definition
tachycardia
peripherial vasoconstriction
renal conservation of blood
increased BMR to give more energy to organs
anaerobic metabolism
Term
why is there anaerobic metabolism in nonprogressive shock
Definition
energy made is not supplied by enough O2 so it is made through carb breakdown
Term
what are the signs of the progressive stage of shock (6)
Definition
heart cannot make enough CO for the body
BP falls and patient becomes cold and clammy (hot in septic shock)
urine output is absent
pulses are fast and week
respiration falls
loss of conciousness
Term
what classifies the irreversible stage of shock
Definition
cardiac, hepatic, renal, respiratory, pancreatic, GI, hematological, neurological failure
no response to treatment
death is imminent
Term
what is the morphology of shock in the brain (2)
Definition
ischemia
enceohalopathy
Term
what is the morphology of shock in the heart (3)
Definition
coagulative necrosis
subendocardial hemorrhage
contraction band necrosis
Term
what is the morphology of shock in the kidney (4)
Definition
tubular necrosis
oliguria
anuria
electrolyte imbalance
Term
what is the morphology of shock in the lungs
Definition
only has symptoms in sepsis or trauma which causes alveolar damage
aka shock lung
Term
what is the prognosis of shock
Definition
varies with origin and duration
80-90% young healthy people with hypovolemic shock survive
75% of people with cardiogenic shock associated with MI or sepsis from gram negative bacilli die
Term
what is multiorgan dysfunction syndrome
Definition
dysfunction of physiological effects of shock
Term
what are the 5 effects in multiorgan dysfunction syndrome
Definition
cardiac depression
respiratory disreess
renal failure
disseminated intravascular coagulation
organ failure
Term
what is the number one complication of athlerosclerosis, why is this so important
Definition
cardiovascular disease
it is the number one killer in the world
Term
where does athlerosclerosis like to form, give 4 examples
Definition
large and medium arteries
aorta, coronary, popliteal, cerebral
Term
what are the two major complications of athlerosclerosis
Definition
MI (heart attack)
stroke
Term
what are 10 risk factors for athlerosclerosis
Definition
age 40+
male (estrogen protects)
FH- hyperlipidemia, cholesteromeia
smoking
hyperlipidemia - diet
hypertension causing vessel stress
diabetes increases lipids in blood
no exercise
obesity
stress
Term
what is the major indicator for athlerosclerosis under 40
Definition
hyperlipidemia - poor diet
Term
why does hyperlipidemia/ hypercholestolemia increase athlerosclerosis
Definition
plaque contains cholesterol so increases in the blood increase chance of plaque formation
Term
what are 4 causes of hyperlipidemia/ hypercholesterolemia
Definition
diabetes
myededma
nephrotic syndrome
familial
Term
what is the treatment of hyperlipidemia/ hypercholesterolemia
Definition
diet and exercise
cholesterol decreasing drugs
Term
other than a general increase in cholesterol for plaque formation, why is hyperlipidemia one of the MAJOR causes for athlerosclerosis
Definition
it can cause athlerosclerosis all alone. it dosent need other factors to help
Term
what type of dietary fat increases cholesterol and athlerosclerosis risk
Definition
trans fat
Term
what type of dietary fat decreases/dosent change cholesterol and decreases/dosent change athlerosclerosis risk
Definition
omega 3 FA
polyunsaturated fats
Term
what is the function of LDL, what is its impact on athlerosclerosis
Definition
delivers cholesterol to tissues
increases athlerosclerosis risk
Term
what is the function of HDL, what is its impact on athlerosclerosis
Definition
transports cholesterol to the liver for bile excretion
decreases athlerosclerosis risk when >60mg/dL
Term
in what 5 ways does smoking increase risk for athlerosclerosis
Definition
decreases HDL

increases CO which causes COHb which causes hypoxia which increases risk

increases platelet adhesion

inncreases permeability of endothelium

nicotine increases sympathetic nervous system
Term
what is the most midifable risk factor for athlerosclerosis
Definition
hypertension
Term
what happens if hypertension goes untreated
Definition
50% die of ischemic heart disease and CHF
Term
what is a sign of long term hypertension
Definition
LV hypertrophy
Term
why does diabetes cause hypertension
Definition
increases platelet aggregation
increases LDL
decreases HDL
Term
where does homocystine comes from
Definition
methionine metabolism
Term
how does homocystine cause athlerosclerosis
Definition
inhibits anti-coagulants
causes epithelial damage
Term
where is CRP made, by what stimulation
Definition
intima of athelosclerosis
released by inflammation
Term
what levels of CRP are a concern
Definition
1-3mg/L
Term
what can CRP perdict
Definition
MI, stroke, peripherial artery disease, sudden cardiac death (even in healthy people)
Term
how does CRP cause athlerosclerosis
Definition
released from plaque
causes adhesion and thrombus
Term
why do we know CRP has to do with athlerosclerosis
Definition
it decreases with less smoking, exercise, and statins
Term
what three microbes cause athlerosclerosis
Definition
chalmydia pneumonia
herpes
CMV
Term
how do microbes cause athlerosclerosis
Definition
initiate inflammatory response
Term
what are the three layers of an athlerosclerosis
Definition
intima: fibrous cap then necrotic center
media
Term
what is in the fibrous cap of a athlerosclerosis
Definition
smooth muscle
macrophages
foam cells
WBC
collagen
elastin
neurovascularization
Term
what is in the necrotic center of an athlerosclerosis
Definition
cell debris
cholesterol
foam cells
calcium
Term
what are three stages of athlerosclerosis , which cause disease
Definition
1. fatty streak
2. fibrous plaque - disease
3. complex lesion - disease
Term
what are the three stages in the formation of a fatty streak
Definition
initial lesion
fatty streak
intermediate lesion
Term
what occurs in an initial lesion
Definition
some macrophages and foam cells gather
Term
what occurs in a fatty streak
Definition
lipid addition intracellulary in intima
increase in macrophages and foam cells
Term
what is a foam cell
Definition
smooth muscle filled with lipid
Term
what occurs in a initial lesion
Definition
increased intracellular lipid and addition of extracellular lipid
stays here for 20 years and digresses or pauses
Term
what are the two stages of fibrous plaque formation
Definition
atheroma
fibrous atheroma
Term
what occurs in an atheroma
Definition
increased intracellular lipids
formation of core of extracellular lipids
Term
what occurs in a fibro atheroma
Definition
many extracellular lipid cores corm
fibrotic, Ca, collagen, SM covering accumulation
Term
what are the complications of a complex lesion
Definition
surface defect: ulcer
hematoma
hemoorrhage
thrombus
scar tissue formation
occlusion
Term
what are the 10 complications of athlerosclerosis
Definition
hemorrhage
ulceration
scar tissue
narrowing
ischemia
thrombosis
emboli
weakening of lg arteries (aorta)
coronary artery disease
peripherial artery disease
Term
what starts the athlerosclerosis process
Definition
endothelial unjiry
smooth muscle migration and proliferation
macrophages eating lipids
Term
what causes endothelial injury
Definition
smoking
immune system
mechanical stress: hypertension
Term
what type of disease is athlerosclerosis classified as
Definition
VISCOUS INFLAMMATORY PROCESS
Term
why does athlerosclerosis cause hemorrhage
Definition
sudden obstruction
Term
what does athlerosclerosis cause thrombosis
Definition
turbulence, slowing
Term
what vessels does athlerosclerosis usually infarct
Definition
heart
extremities
kidney
SI
brain
Term
what is the normal outcome of athlerosclerosis in a medium size vessel
Definition
ischemia, infarct, occlusion
Term
what is the normal outcome of athlerosclerosis in a large vessel
Definition
weakening of vessel wall
Term
how is LDL removed
Definition
LDL recepors in liver
scavenger receptors on macrophages and monocytes
Term
what stimulates for macro and mono to eat LDL
Definition
damaged (oxidixation or modification)of LDL
Term
what happens when lots of LDL is dammaged and macrophages and monocytes keep eating it
Definition
cholesterol ester formation inside them makes them a foam cell
Term
plaque formation at the fatty streak level beins with monocyte attachment, then what do they do to cause propogation
Definition
migrate to subendothelium
mature to macrophages
release ROS...

ROS oxidizes LDL so it cannot be taken into liver
macrophages eat LDL making more foam cells

LDL/ROS cause endothelial damage which causes platelet adhesion which releases growth factors which increases collagen, elastin, and proteoglycens

endotheliam damage causes endothelium derived releasing factor inhibition and LDL antibody production which causes vasospasm

lymphocyte and monocyte chemotaxis due to damage
Term
what determines if there will be ulceration of a plaque
Definition
strength and Ca content of outer layer stimulated by GF release from adhering platelets
Term
why do lymphocytes and monocytes come to plaque
Definition
damage to endothelium
Term
why does the immune system make antibodies to the plaque
Definition
endothelial damage
Term
why is there vasospasm around a plaque
Definition
anti-LDL antibodies
decrease in endothelium derived releasing factor

due to endothelial damage
Term
define coronary artery disease
Definition
cardiac disease caused by impaired coronary flow
Term
what are 5 causes of coronary artery disease, which is the most common
Definition
1. athlerosclerosis
MI
dysarrhythmia
cardiac failure
suddent cardiac death
Term
what is the most common cause of Mi, why
Definition
athlerosclerotic plaque deposits
Term
what is the cut off point for coronary a disease diagnosis, why
Definition
at 75% occlusion vasodilation cannot compensate anymore
Term
what are the two types of coronary artery disease and their mechanism
Definition
stable/fixed lesion: chronic disease. silent MI, etc

unstable/vulnerable lesion: can rupture (plaque dysruption) causing platelet adhesion and thrombosis
Term
what is the tx for coronary a disease
Definition
antiplatlet drugs avoid formation of blockage after rupture avoiding thrombosis (asprin)
Term
define peripherial artery disease
Definition
obstruction of large arteries not within coronary, aorta, or brain
Term
what are causes of peripherial artery disease
Definition
athlerosclerosis blockage
inflammation
embolism
thrombus
Term
what is the mechanism causing problems in peripherial artery disease
Definition
acute or chronic ischemia
Term
what are the risk factors for PAD
Definition
same as athlerosclerosis
Term
PAD symptoms
Definition
pain
weakness
numbness
cramping
sores
wounds
ulcers
slow healing
bluness, paleness
coolness
less hair and nail growth
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