Pathophysiology Test 2 USF
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- What does plasma contain?
- Mostly water, proteins (albumin, fibrinogen, antibodies (IgG most), soluble substances like nutrients, resp. gases, wastes
- Hematocrit
- Total volume of formed elements/total volume of blood
- Hematopoeisis
- All blood cell formation
- Erythropoeisis
- Formation of red blood cells
- Leukopoeisis
- Formation of white blood cells
- Basic facts on erythrocytes
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anuclear
no mitosis
live 120 days - Transferrin
- transfer form of iron
- Ferritin
- storage form of iron in liver
- Hemoglobin structure
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globin - 4 polypeptide chains (2 alpha, 2 beta)
heme - each chain has a heme group - iron.
1 hemoglobin = 4 oxygen - oxyhemoglobin
- saturated hemoglobin, carrying 4 oxygen
- Hemoglobin A
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normal adult,
2 alpha, 2 beta chains - Hemoglobin F
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produced during fetal life up to 3-6months
2 alpha, 2 F chains - Stimulus for erythropoeisis
- Low tissue oxygen, stimulates secretion of erythropoetin, which stimulates RBC production
- Polycythemia (erythrocytosis)
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Too many RBC's
excess RBC's increases vessel wall pressure, causes high BP - Primary Polycythemia
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rare neoplastic disease
stem cell to become RBC gets altered - RBC cancer
white males 40-60
flushed face, thrombi, hypertension.
viscous blood from too many RBC's, causes platelets to spontaneously activate, causes thrombi - Secondary polycythemia
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Usually caused by prolonged hypoxia
could be normal physiologic response to:
tissue hypoxia (heart & lung)
high altitudes
heavy smoking (CO2 takes place of oxygen on hemoglobin, bonds easier)
marrow responding to kidney increasing output of EPO - Autologous transfusion blood doping
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remove own blood, reinject later.
inc. risk blood clots, hypertension - Synthetic EPO blood doping
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EPO taken for renal failure
stimulates more RBC production - Homologous transfusion blood doping
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easiest to trace
blood from someone w/ same blood type - Anemia
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reduction of normal Hb in blood
may be due to:
abnormal Hb
reduced # RBC's (dec. prod, blood loss, inc. destruction)
structural abnorm. of RBC's
ALL ANEMIAS - transp. of oxygen is impaired. can't enter Kreb's, produce lactic acid. - Hemolytic Anemia
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normocytic/normochromic (normal size, normal amt. Hb)
premature RBC death
jaundice
liver can't keep up with excess bilirubin, builds up in connective tissue - Spherocytosis
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hemolytic anemia
autosomal dominant disorder expressed when heterozygous - 50% passed to children, M or F
abnormal spectrin AND ankyrin leads to spherical RBC shape
normocytic, but wrong shape, harder to get through capillaries, clogs up spleen - spleenomegaly
RBC ruptures easily in tight curves of spleen
spleenectomy helps - Sickle cell anemia
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blacks/equatorial descent
autosomal recessive disorder
genetic defect in beta Hb chains - valine in place of glutamic acid
homozygous - sickle cell disease
heterozygous - sickle cell trait - Homozygous Sickle Cell Anemia
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Sickle cell disease, symptomatic
produce only HbS, no HbA
all beta chains are S chains, which combine with normal alpha chains to form HbS
cells only sickled in venous blood
sickled RBC lives 10-14 days - Heterozygous sickle cell anemia
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both normal beta and S chains are synthesized
can be symptomatic in times of stress.
asymptomatic if producing at least 40% HbA - Clinical manifestations of sickle cell anemia
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symptoms first noticed 6mo-1yr age (growth puts more demands for oxygen, out of HbF)
low hematocrit
sickling or hemolytic crisis may occur spontaneously, usually induced by fever, resp. disease, pregnancy, stress
peripheral tissues deprived of oxygen due to massive blockage of capillaries.
blood transfusion to treat - Complications of hemolytic anemias
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pigmentary gall stones (inc. bili in bile, supersaturated, crystallizes and becomes a stone)
jaundice
stroke (rbc's cause traffic jam to cerebral arteries)
neuro complications (high bili is toxic to CNS)
survival: 40-50yrs, stroke, MI
bone transplants, blood transfusions successful
hydroxyurea - med decreases painful episodes, inc prod of HbF
gene therapy, nitric oxide therapy (dilates vessels so sickled cells get through easier) - Immune Hemolytic Anemia
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ex. drug induced anemia
penicillin for some people is a hapten, attaches to RBC proteins. type II sensitivity, tissue specific destruction
idiopathic (unknown cause) - Iron Deficiency Anemia
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most common, more prev. in women
detrimental to dev. of NS
microcytic, hypochromic (small cells, not as much Hb)
low hematocrit
poikilocytosis (abnormal shape possible)
Causes: menstruation, bleeding ulcer, defic. iron rich foods - Pernicious anemia
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malabsorption of vit. B12 due to lack of gastric intrinsic factor
vit b12 req. for normal DNA synthesis
lack of parietal cells, which produce intrinsic fact, which binds with B12 in stomach, enters small int., absorbed by epithelial cells of small int., sent into bloodstream
schilling test - measures b12 absorption w/ radioact b12 - Causes of pernicious anemia
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avoidance of dietary b12
atrophic gastritis complications(small parietal clls, less intrinsic factor)
gastric bypass (many parietal cells removed)
Crohn's or other malabsorption syndrome
Autoimmune - antibodies against parietal cells or intrinsic factor
Vit b12 injections directly into bloodstream for treatment - Aplastic anemia
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panctyopenia (many cells affected, low numbers of RBC's, WBC's, dec. thrombocytes) shows up in lab findings
fatigue, pale, inc. infection risk, bruising, excessive blood loss - Idiopathic aplastic anemia
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underlying autoimmune disease?
therapy may require bone marrow transplant - Secondary aplastic anemia
- caused by cytotoxic drugs, radiation therapy or viral infection
- Infectious mononucleosis
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Epstein-Barr virus (B-cell lymphoma link)
infects pharyngeal epithelial cells --> adjacent lymph tissue --> B cells w/ EBV receptors --> infected B cell w/ EBV genome becomes plasma cell --> heterophil antibodies
heterophil antibodies bind to RBC proteins in sheep
4-8 week incubation period
T-cytotoxic cells destroy infected cells - Malignant lymphomas
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tumors arising in the cells of lymphoid tissue
6th most common cause of cancer death in the US - Hodgkin Disease
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young adults and those over 50
Reed-Sternberg cell (probably a transformed macrophage)
cure rate high w/ radiation, chemotherapy
lymph adenopathy (swollen nodes) tired - causes an anemia, increased inf. risk
produce excessive interleukin 13 which leads to proliferation of immune cells - Non-Hodgkin Lymphoma
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more frequent than Hodgkin
numerous subtypes (T or B cell, mostly B) Epstein-Barr virus??
Human t-lymph virus??
herbicides??
Rituximab (drug) binds CD20 on B cell lymphomas and controls proliferation. CD20 NORMALLY causes cells to proliferate
SV40 virus - 40% infected with this, only prior known to inf. rhesus monkey. polio vaccine? - Leukemia
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means "white blood"
neoplastic cell in blood and bone marrow
derived from stem cells
type of leukemia based on which stem cell failed - Causes of leukemia
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most common childhood cancer
high levels of radiation
anti-tumor drugs
down's syndrome (10x more than normal)
virus (human T lymphocytic virus (HTLV) type 1 and 2) - Clinical features common to all leukemias
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leukoblasts (immature WBC's) larger than WBC's
bone marrow contains malignant cells
leukostasis (WBC's thicken blood flow)
lymphadenopathy, hepatomegaly, splenomegaly
complications: anemia, recurrent infections, uncontrollable bleeding (WBC production takes all resources) - Acute Lymphoblastic Leukemia (ALL)
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most common malignancy affecting children
breastfed children at dec. risk
chemotherapy successful - Acute myelogenous leukemia (AML)
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myeloid stem cell leukemia, can present in many ways
many subtypes, most common: acute granulocytic leukemia (neutrophils, basophils, eosinophils)
presents after middle age
down syndrome inc. risk
clinical trials under way for vaccine - Chronic Lymphocytic Leukemia (CLL)
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30% of all leuk. in US
95% of cases a malignant B cell precursor is at fault
asymptomatic at time of Dx
usually affects older adults
error: bcl-2 gene apoptosis - Chronic Myelogenous Leukemia
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Philadelphia chromosome (unique)
30-50yrs old
bone marrow transplant, chemo
long arm of chrom 9 fused w/ short arm of chrom 22 which puts BCR and ABL gene next to each other, which stimulates all to proliferate and differentiate - Arteriosclerosis
- no cholesterol plaque, just hardening of arteries
- atherosclerosis
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cholesterol plaque (atheroma) present, arteries hardened.
underlying disease process in most coronary artery diseases that cause MI, and arterial alterations that produce CVAs
can affect any artery in body
develops from birth, significant in 20's - top 5 arterial locations for atherosclerosis, know in order
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1. abdominal aorta and iliac arteries
2. coronary arteries
3. thoracic/femoral
4. internal carotids
5. cerebral - atherosclerosis risk factors
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age - men over 45, women over 55 (estrogen deters)
gender - more males than premenopausal females, equal after menopause
genetic predisposition:
familial hypercholesterolemia (mutated LDL receptor), sibling history
EBT (electron beam tomography) measures calcium deposits in arteries - hypercholesterolemia
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primary causes: defective synthesis of apoproteins(lipid carriers), lack of receptors
secondary causes: obesity, DM, inc. cholesterol ingestion, excess calorie intake (lowers HDLs), inc. saturated fats - lipoprotein
- apoprotein + lipid
- dietary lipids
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lipids are insoluble in plasma
mostly triglycerides, some cholesterol, some phospholipids
transported in blood by lipoproteins. protein component = apoprotein (ex. A, B, C, E) - Classification of lipoproteins
- by density (more protein = higher density)
- Low density lipoproteins
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chylomicrons - major triglyceride carriers, 2% protein
LDL - 10% triglyceride, 50% chol, 25% protein - high density lipoproteins
- HDL - 50% protein, 20% chol., 5% triglycerides
- hypertension
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inc. bp, norm <120/<80
prevalence inc. with age
more common in men than women, equal after menopause
more common in blacks - Primary hypertension (aka essential hypertension)
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inc. BP existing in absence of another major disease
risk: FH, old age, black, obese (inc. periph resistance), type II diabetes, oral contraceptives, high salt intake - cardiac output
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stroke volume x heart rate
approx. 70mL
amount ejected from each ventricle during contraction - What is arterial blood pressure related to?
- Cardiac output and peripheral resistance.
- Hyperhomocysteinemia
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homocysteine inhibits components of the anticoagulation cascade
inc. homocysteine promotes clotting
taking folate dramatically reduces risk of this, which reduces atherosclerosis and therefore MI and stroke risk - tobacco use and hypertension
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smoking pack/day increases likelihood of coronary thrombosis and MI
when acute MI occurs, more likely to be fatal
tobacco damages vascular endothelium and enhances platelet aggregation
smoking lowers HDL levels
nicotine stimulates release of EP and NOREP which inc. heart rate (nicotine patches too!) - C-reactive protein
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released from liver
serum marker of systemic inflammation, can be lowered with statins - pathophysiology of atherosclerosis
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1. damage occurs in tunica intima where blood/arterial wall interface
2. blood platelets and lipoprotein deposit
3. platelets release growth factors that penetrate vessel wall (proliferation of smooth muscle, attracts calcium into tunica media layer)
4. monocytes adhere to the injured endothelium, engulf lipoproteins by foam cell, which leads to fatty streaks
5. proliferating smooth muscle and fibroblast surround, fatty streak --> plaque, atheroma. start depositing connective tissue to cover the fatty streak - complications of atherosclerosis
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1. thrombosis and embolism - pressure of lipid soft region may cause fibrous capsule to rupture --> ulceration. contents of atheroma highly thrombogenic --> blood clot.
2. acute arterial occlusion - occurs at bifurcations: aorta, iliac and femoral, popliteal... pulse pressure decreases downstream of occlusion - cardiovascular disease
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#1 cause of death in US
1 in 3 MI die within hour
coronary artery disease leads to myocardial ischemia leads to myocardial infarction - male MI symptoms
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left side pain jaw - right arm
fatigue
crushing pain - female MI symptoms
- fatigue
- chronic atherosclerosis
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more time for alternate blood vessel pathways to form
leads to stable angina or silent MI - acute atherosclerosis
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no time for alternate blood vessel pathways to form
leads to MI, unstable angina - angina pectoris
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clinical manifestation of myocardial ischemia
intense pain, buildup of lactic acid and/or irritation of myocardial nerve fibers
stable, unstable, variant - stable angina
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narrowing of lumen due to fixed plaque
relieved by rest or nitroglycerin (vasodilator) - unstable angina
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cannot be predicted
attacks increase w/ frequency
caused by vasospasms and atherosclerotic lesions
treat w/ heparin (blood thinner) - variant angina
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attacks almost always while at rest
vasospasm of 1 or more of the major coronary arteries - blockage in left coronary artery
- affects left atrium
- blockage in right coronary artery
- affects right ventricle, right atrium
- blockage in posterior descending branch of right coronary artery
- affects right and left ventricle
- blockage in left coronary artery, circumflex branch
- affects left atrium, left ventricle
- blockage in left coronary artery, anterior descending branch
- affects left ventricle, right ventricle
- extent of MI depends on
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1. location of occlusion
2. degree of blockage
3. collateral circulation - therapy for myocardial ischemia
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nitrates (vasodilator)
anti-platelet drugs (aspirin, platelet receptor antagonist so it prevents clotting)
block beta-adrenergic receptors- found in cardiac cells, binds epinephrine
calcium channel blockers - lower contractile force of cardiac cell
coronary artery bypass graft - alternate route around occlusion (usually saphenous vein or internal mammary artery)
percutaneous coronary intervention (+ stent) - balloon catheter, squishes plaque, stent keeps bv open - temporary ischemia
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<20 minutes
leads to angina + reversible cell injury - prolonged ischemia
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>20 minutes
leads to MI + irreversible cell injury --> scar tissue - Leading locations of MI
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1. blockage in anterior descending
2. blockage in rt. coronary artery - SERUM MARKERS FOR MI
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CK-MB - creatinane kinase - MB, shows up 4-8 hrs post MI. enzyme in myocardial cells involved in ATP prod. if found in blood, MI occured and dead cells were lysed
Myoglobin - oxygen carrying molecule in muscle cells, increases about 1hr post MI (any muscle)
troponin levels - inc. within 3 hours of MI
CRP - c reactive protein, inc. prior to or following MI - sequelae of acute MI
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1. arrythmias - most serious is ventricular fibrillation
2. cardiogenic shock - decline in cardiac output when 40% of LV myocardium has died
3. thromboemboli
4. healing of infarcted tissue
5. aneurysm
6. rupture (survive? cardiac tamponade - pericardium full of fluid, pushes on heart, makes contraction difficult) - Right sided congestive heart failure manifestations
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peripheral tissue congestion
congested liver w/ impaired liver function --> dec. clotting factors, dec. albumin --> edema. event. jaundice
edema, ascites
GI congestion - anorexia, wt. loss, GI distress - Left sided congestive heart failure manifestations
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dec. cardiac output --> activity intolerance --> dec. tissue perfusion
pulmonary congestion --> impaired gas exchange, pulmonary edema, cough, dyspnea, cyanosis and signs of hypoxia - Acute pericarditis
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chest pain that worsens w/ resp.
inc. capillary permeability --> fibrous deposits
friction rub
anti-inflammatory agents to treat - Dilated cardiomyopathy
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ventricular dilation leads to dec. stroke volume, inc. end-diastolic volumes
alcohol?
dyspnea, fatigue, sometimes inc. BP
treatment: vasodilators and diuretics - Valvular Dysfunction
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endocardium disorder
aortic stenosis (narrowing)
causes: rheumatic disease (strep bact)
congenital defect
calcification
diminished stroke volume - Mitral stenosis
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causes: acute rheumatic fever, bacterial endocarditis
increased atrial pressure, atrial hypertrophy, atrial dilation
pulmonary congestion, rt. ventricular failure - aortic regurgitation
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causes: rheumatic fever, Marfan syndrome (mutated fibrilin) and hypertension
heart murmur
large stroke volume
dysrhythmias - Mitral regurgitation
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causes: mitral valve prolapse, rheumatic heart disease
atrial dilation
pulmonary hypertension - mitral valve prolapse
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thickened mitral cusps
long chordae tendinae
end result, the valve doesn't close as well, causes mitral regurgitation