Term
|
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
|
|
Term
| what is the usually route of an venous emboli |
|
Definition
|
|
Term
| what is the usually route of an portal vein emboli |
|
Definition
|
|
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
|
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
|
|
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
|
|
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
|
|
Term
| what are the common consequences of a large emboli (2) |
|
Definition
sudden death
saddle emboli |
|
|
Term
|
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
|
|
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
|
|
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
|
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
|
|
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
|
Definition
| active increased inflow of blood to tisue causing redness |
|
|
Term
|
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
|
Definition
| accumulation of blood in the tissue |
|
|
Term
| what is an example of a hematoma |
|
Definition
| dissecting aortic aneurysm casuses retropreotineal hematoma |
|
|
Term
|
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
|
Definition
|
|
Term
| what are the causes of purpura |
|
Definition
|
|
Term
|
Definition
| >1-2cm subcutaneous hematoma |
|
|
Term
| what is the cause of ecchymoses |
|
Definition
|
|
Term
| why does ecchymoses change color |
|
Definition
| RBC are degraded by macrophages (Hb > bilirubin > hemosiderin) |
|
|
Term
|
Definition
| crush injury ruptures myocardium or coronary A and blood traps in pericardium |
|
|
Term
| what is complication of hemopericardium |
|
Definition
|
|
Term
|
Definition
| massive breakdown of RBC releases bilirubin |
|
|
Term
| what are the two sites of congestion |
|
Definition
|
|
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
|
|
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
|
|
Term
| where is the most impact of vascular tone occuring at |
|
Definition
|
|
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
|
|
Term
| what are the factors that affect local arteriole regulation |
|
Definition
|
|
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
|
|
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
|
|
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
|
|
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
|
|
Term
| what are 4 characteristics of a malignant tumor |
|
Definition
anaplasia (most of the time)
metastasis
erratic growth
mitotic figures |
|
|
Term
|
Definition
cells without polarity organization
usually loss of differentiation
many abnormal mititoc figures |
|
|
Term
|
Definition
| can invade adjacent tissue and spread to distant sites in the body |
|
|
Term
|
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
|
Definition
| cells vary in size and shape |
|
|
Term
|
Definition
|
|
Term
|
Definition
| dysplasia through entire epithelial thickness but not BM (pre-invasive cancer) |
|
|
Term
|
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
|
Definition
swelling
(for neoplasms and non-neoplasms) |
|
|
Term
| name the root for: fibroblasts, myxoid, cartiladge, osteoblasts, fat |
|
Definition
|
|
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
|
|
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
|
|
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
|
|
Term
| what are the 2 least common places for cancer spread |
|
Definition
|
|
Term
| where does a cracinoma usually spread |
|
Definition
|
|
Term
| where does a sarcoma usually spread |
|
Definition
|
|
Term
| where does colon carcinoma usually spread |
|
Definition
| penetrates gut wall and spreads to peritoneal cavity |
|
|
Term
| where does lung cancer usually spread |
|
Definition
|
|
Term
| where does ovarian cancer usually spread |
|
Definition
|
|
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
|
|
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
|
|
Term
| what is the common cause of cancer in the young |
|
Definition
|
|
Term
| what is the most common cancer in japan |
|
Definition
|
|
Term
| what is the most common cancer in us |
|
Definition
|
|
Term
| what is the most common cancer in africa |
|
Definition
|
|
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
|
|
Term
| what is the most common origin for cancer over 4yo |
|
Definition
|
|
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
|
|
Term
| example of leukplakia of oral cavity, vulva, or penis causing cancer |
|
Definition
|
|
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
|
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
|
|
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
|
|
Term
|
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
|
|
Term
|
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
|
|
Term
| what kind of cancers are HPV very commonly involved in |
|
Definition
| 75% of squamous cell carcinoma and 100% of preneoplastic disorders (dysplasia) |
|
|
Term
|
Definition
| kaposki sarcoma associated herpes virus |
|
|
Term
| what two parts of HPV cause problems |
|
Definition
|
|
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
|
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
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
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
|
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
|
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
|
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
|
|
Term
| what is the problem in LeFraumini syndrome |
|
Definition
|
|
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
|
|
Term
|
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
|
|
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
|
|
Term
| what gene mutations cause loss of tumor supression (3) |
|
Definition
|
|
Term
| what gene mutations cause stop of apoptosis (3) |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
hemorrhage
trauma of burns
MI
pulmonary embolism
sepsis |
|
|
Term
|
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
|
Definition
cardiogenic
hypovolemic
septic
neurogenic
anaphylactic |
|
|
Term
| what causes cardiogenic shock |
|
Definition
| myocardiacal pump failure |
|
|
Term
| what are 2 examples of cardiogenic shock |
|
Definition
|
|
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
|
|
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
|
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
|
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
|
|
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
|
|
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
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
Term
| why does diabetes cause hypertension |
|
Definition
increases platelet aggregation
increases LDL
decreases HDL |
|
|
Term
| where does homocystine comes from |
|
Definition
|
|
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
|
|
Term
|
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
|
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
|
|
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
|
|
Term
| what does athlerosclerosis cause thrombosis |
|
Definition
|
|
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
|
|
Term
|
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
|
|
Term
| why does the immune system make antibodies to the plaque |
|
Definition
|
|
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
|
|
Term
|
Definition
pain
weakness
numbness
cramping
sores
wounds
ulcers
slow healing
bluness, paleness
coolness
less hair and nail growth |
|
|
