deck_3466489 Flashcards
(163 cards)
1
Q
How many protein-coding genes in Human Genome Project
A
19,000
2
Q
Mutations affecting ___ cells can be inherited (basis of genetic disease)Mutations affecting ____ cells can result in tumors (usually not inherited/passed along)
A
GermSomatic
3
Q
Which type of mutation alters reading of RNA
A
Frameshift mutations
4
Q
Fragile X syndrome is what type of mutation?
A
Trinucleotide repeat mutation
5
Q
Where are polymorphisms usually found?What are their significance for disease?
A
NON coding regions (i.e. introns & exons)They are markers
6
Q
Copy number variation is an example of a ____, therefore, it’s recognized as a ____
A
polymorphismmarker
7
Q
Epigentic change is a ___ that reduces/shuts down ____ by:
A
polymorphismtranslocation (protein synth)methylation of cytosine residues
8
Q
Which polymorphism controls gene silencing?
A
Micro-RNA’s
9
Q
Autosomal ___ disorder will be evident clinically when only one of the chromosomes in the pair (heterozygous) exhibits a mutation
A
dominant
10
Q
Majority of automsomal ____ create outward physical changes.Early/late age of onset?Example:
A
dominantLATE (even though mutant gene is present from birth)Huntington’s Disease
11
Q
If one of the parents is infected and half the offspring are affected, it’s autosomal ____
A
dominant
12
Q
Which disease has nearly 100% penetrance
A
neurofibramotosis
13
Q
What is variable expressivity?
A
Trait is seen phenotypically, but is expressed differently among individuals
14
Q
De novo mutation:
A
If a kid has an autosomal disorder and neither of the parents have it
15
Q
Which is a largest group of mendelian disorders?
A
Autosomal recessive
16
Q
For autosomal recessive, do the parents usually show the disease?
A
NO
17
Q
Autosomal ___ is when you need a germline from both parents to develop disease
A
recessive
18
Q
Autosomal recessive commonly effects enzyme for:
A
metabolism
19
Q
For autosomal recessive, the age is onset is ___ in lifeThe expression tends to be ___ uniform and ___ penetrance is common
A
earliermore uniformcomplete penetrance
20
Q
X-linked disorders are almost always (dom/rec)If a man inherits an x-linked recessive (almost all are recessive), is he always affected?
A
RecessiveYES
21
Q
When lyonization occurs, what is left in the female zygote?What is unfavorable lyonization causes clinical evidence of an _____ disease in a ___zygote.- Example:
A
Barr bodyx-linked disease in a heterozygote.Ex. hemophilia A
22
Q
A patient has coarse facial features, clouding of cornea, joint stiffness, and mental retardation. They have _____ which is due to lack of _____. It’s a _______disease
A
-Mucopolysaccharidoses -Lack of enzyme to degrade mucopolysachharides-Lysosomal Storage Disease
23
Q
What are some things that come from MULTIFACTORIAL inheritance?Frequency of inheritance:
A
-Physiologic traits (i.e. height, weight, hair color, BP, etc)-Common diseases (i.e. diabetes, hypertension, gout, schizo)-2-7%
24
Q
Prevalence of newborns that have a chromosomal abnormality:In as many as __% of 1st trimester spontaneous abortions, the fetus has a chromosomal abnormality
A
1/20050%
25
Euploid:Polyploidy:Aneuploidy:Trisomy:Monosomy:
-Euploid: normal -Polyploidy: multiple of 23 (SPONTANEOUS ABORTION)-Aneuploidy: any number that is not exact multiple of 23 (ASSOCIATED W MANY NEOPLASIAS -CANCER)-Trisomy: 1 extra chromosome-Monosomy: 1 less chromosome
26
Translocation:Reciprocal translocation:Deletion:Inversion:
-Translocation: transfer of a part of 1 chromosome to another nonhomologous chromosome-Reciprocal translocation: fragments are exchanged between 2 chromosomes-Deletion: loss of a portion of a chromosome-Inversion: chromosome breaks in 2 points, then the released fragment turns around and then reunites
27
Indications for genetic analysis..Prenatal:Postnatal:
PREnatal:-Mother \>34yrs old-Parent is carrier of chromosomal translocation/ or x-linked disorderPOSTnatal:-Multiple congenital anomalies-Mental retardation-Infertility
28
What does arteriosclerosis due to arteries
harderns arteries
29
Which type of arteriosclerosis is calcification WITHOUT luminal narrowing or disruption (so blood flow is ok)
Monckeberg's
30
Difference of hyaline and hyperplastic arteriosclerosis..-which causes narrowing of lumen?-which causes thickening of basement membrane?-which causes fibrocellular intimal thickening-which is more affected by diabetes?
-hyperplastic = narrowing of lumen-hyaline = thickening of basement membrane-hyperplastic = fibrocellular intimal thickening-hyaline more affected by diabetes
31
What disease is responsible for more death than any other?
Vascular disease
32
Arterial vs. Venous side...Which is high pressure?Which has strong muscular wall?Which has a more elastic wall?Which has a larger lumen?
Arterial = high pressureArterial = strong muscular (to withstand pressure)Venous = elastic wallVenous = larger lumen (dilates easily)
33
Death rate for all atherosclerosis?\_\_% due to MI
50%25% due to MI
34
What is the most important NON-modifiable risk factor for arteriosclerosis?
Genetics (family history of MI)
35
What modifiable risk factor for arteriosclerosis increases death rate by 200%?What is a risk factor in the oral cavity?
smokinginflammation (CRP- inflammatory marker)
36
Atherosclerosis: response to injury hypothesis...-Endothelial injury results in endothelial dysfunction-Accumulation of lipoproteins-Monocyte adhesion =
Monocyte adhesion = migration into intima w/ differentiation into macrophages and "foam cells" (macrophages that have ingested lipid)
37
Atherosclerotic plaque (an atheroma) has a ____ cap, a _____ core and has progressive changes (which includes \_\_\_\_\_)
fibrous capcentral lipid corefissure formation
38
Fatty streaks occur in what age?They can be in atherosclerotic and nonatherosclertoic prone geographic areas and are characterized by:
Infants and childrenLipid-laden cells in the intima
39
A complication of ATHEROSCLEROSIS that's due to pressure atrophy of the media w/ altered balance of collagen synthesis/degradation is?-It leads to?-Other complications?
AneurysmSudden death-gangrene, renal artery stenosis (atrophy of kidney)...
40
Hypertension prevalenceNormal?Severe?
25%Normal 160/106
41
Which type of hypertension accounts for 90%?What are some contributing factors of essential hypertension?What symptoms do most patients have?
Essential hypertensionGenetics, stress, obesity, increased salt intake, smokingNONE until organ damage has already occured!
42
With Essential Hypertension, what happens during compensation?What happens if you add dilation?
Concentric left ventricular hypertrophy...the muscles get stronger and makes the ventricular chamber smaller (cardiac output at risk)...makes heart pump fasterDilation causes it to be DEcompensated. Big heart but can't pump very well. Leads to CHF
43
Hypertension causes ____ sodium excretion --\> salt and water ___ --\> \_\_\_\_plasma volume and cardiac output
reduced excretionsalt and water retentionincreases plasma volume and cardiac output
44
MALIGNANT hypertension complications:\_\_% live beyond 5 years
Cerebral edema with pailledema, retinal hemoorhage, encephalopathy (brain disease), renal failure50%
45
What is Congestive Heart Failure?Affects how many people in US annually?Contributes to \_\_\_\_deaths
Failure of the heart to pump an adequate amount of blood to supply the metabolic requirements5 million300,000
46
CHF compensatory mechanism..Initially:Then:Activation of neurohumoral system releases ____ w/ increased __ + \_\_\_. Activation of ____ system w/ water/salt retention --\> increased circulatory volume
Initially: Myocardial hypertrophy (helps initially, but the larger muscle fibers require more oxygen from the capillaries, which is not typically available)Then: Frank-Starling mechanism (ventricular dilation)...as you stretch cardiac muscle, it'll push out more forcefullyrelease of NE w/ increased HR + contractility-Activation of renin-angiotensin system
47
Biggest cause of LEFT-side heart failure?Biggest cause of RIGHT side failure?Other causes of right side:
Ischemic heart diseaseLeft side heart failure-pulmonary (lung) hypertension (cor pulmonate), valve disease, septal defects w/ left to right shunts
48
Most common manifestation of CHF:CHF due to __ side leads to __ failureLeft ventricular failure causes ___ edemaRight ventricular failure (caused by left failure causing congestion) causes congestion of ____ AND edema of \_\_\_\_
Left ventricular failure Left failure leads to right failure (cuz left doesn't pump out enough so it congests the right)Pulmonary edema (difficulty breathing while lying down)Congestion of liver and spleen AND edema of feet and ankle
49
Prevalence of Congenital heart disease:What are the two forms:
6/1,000 births Cyanotic (right --\> left) (shunting of poorly-oxygenated venous return to systemic arterial circulation.)Noncyanotic (left--\>right)
50
What are the 2 cyanotic congenital heart diseases?This can cause what clinically:Most common congenital heart disease:
Tetrology of Fallot + Transpostion-clubbing of fingers-Ventricular septal defect
51
Leading cause of death in the US?
Ischemic Heart Disease. 500,000 per year
52
During Ischemic heart disease, narrowing of ____ by at least \_\_% by atherosclerosis. Other factors:
narrowing of coronary arteries by at least 75%Shock, pneumonia, anemia
53
Acute myocardial infarction (a type of \_\_\_\_\_\_)..Clinical presentation:Diagnostic test:Pathology:
Ischemic Heart DiseaseClinical: chest pain, shortness of breathDiagnostic: ECG, elevation of serum enzymes/troponinPath: coagulation necrosis (hours), neutrophil infiltration (days), granulomatous tissue (1 week), scar formation (wks-mos)
54
3 types of cardiomyopathy:
DilatedHypertrophicRestrictive
55
DILATED cardiomyopathy:
dilation of all 4 chambers
56
HYPERTROPHIC cardiomyopathy:
GeneticASYMMETRIC HYPERTROPHY
57
RESTRICTIVE cardiomyopathy:
decrease in ventricular compliance (wall is stiffer)
58
Most common cause of myocarditis:Pathology:
Virus-Viral infection produces a lymphocytic infiltrate w/ foci of necrosis -Hypersensitivity (usually to drugs) causes a perivascular inflammatory infiltrate w/ many eosinophils
59
Mitral Valve Stenosis is failure of valve to:It is a result of acute _____ (which is usually caused by \_\_\_\_).This usually causes \_\_carditis which is characterized by \_\_\_\_bodies which are essentially \_\_\_\_
-Failure of valve to OPEN completely (obstructing forward flow)-repeated Acute Rheumatic Fever (ARF)-Pharyngitis-myocarditis-Aschoff bodies-Granulomatous inflammation
60
MITRAL Valve STENOSIS is thought to be due to the production of _____ against the streptococcal (pharyngitis) bacteria which cross react with various antigens in the heart
antibodies
61
MITRAL Valve REGURGITATION is failure of valve to:2 causes:\*\*\*Histopathologic feature:Mitral valve prolapse is when the leaflets balloon into the __ atrium during \_\_\_ventricular contraction (\_\_\_\_\_).Mild prolapse is very common and occurs in \_-\_% of the populationFloppy mitral valve can be an isolated abnormality or part of a systemic connective tissue disorder such as:
-Failure of valve to CLOSE completely (causing backflow of blood)-IHD and endocarditis-\*\*\*Myxomatous degeneration-Left atrium-Left ventricular contraction (systole)5-10%Marfan syndrome
62
AORTIC valve STENOSIS is caused by ___ and ___ which reduce the valve cusp mobility. This can be due to chronic ____ \_\_\_\_ disease, or may occur with advanced age (\>65). Is the aortic valve usually (bicuspid/tricuspid), and what is a common congenital malformation which ends up with fibrosis by 40
Fibrosis and CalcificationChronic rheumatic valvular diseaseUsually tricuspid (bicuspid is malformation)
63
Infective Endocarditis...10-20% of cases are caused by:3 factors that have been identified as important pathogenesis:Weird clinical manifestations of IE:\*\*Complications... rupture of \_\_\_\_
prosthetic valves1. endocardial/endothelial injury due to blood flow abnormality2. fibrin thrombi3. organisms in blood (sepsis)-Nail bed and retinal (Roth) hemorrhages -rupture of chordae tendineae
64
Acute vs Subacute Endocarditis...Which has large vegetations?Which is longer duration?Which has a more virulent organism?Which has a previously normal valve?Which has more tissue destruction
Large vegetations: AcuteLonger = subacuteMore virulent = AcutePreviously normal valve = acuteMore tissue destruction = acute
65
Vasculitis:What causes vasculitis to be worse?
Inflammation of blood vesselsImmune complexes
66
Giant Cell (temporal) Arteritis...\*\*\*AGE:Pathology:Clinical:\*\*similar to _____ arteritis but in \_\_\_\_px and not specific to ____ (gender)
-OLDER px-Granulomatous inflammation w/ giant cells, fibrosis. Causes narrowing of lumen which decreases blood flow to affected tissues-Weakness/pain of jaw (decreased blood supply)-Takayasu arteritis but in OLDER px and NOT specific to women
67
Takayasu Arteritis...Causes "\_\_\_\_\_\_" disease\*\*\*Similar to \_\_\_\_arteritis but in ___ px and \_\_\_(gender)\*\*\*
"pulseless disease" due to weak pulses in arms)-giant (temporal) but in YOUNGER px and WOMEN
68
Polyarteritis nodosa...Associated with which disease?Why is clinical presentation confusing?Clinical:Most common site of involvement?Healing is only by:
-Hep B-Involves multiple organ systems)-Renal failure which leads to hematuria (blood in urine), and ANEURYSM -Kidney-Fibrosis (which is bad for organs!)
69
Kawasaki Disease...\*\*Suspected that a ___ infection triggers a ___ reaction (aka \_\_\_\_\_).\*\*\*Age group:Clinical:Therapy:
VIRAL infection triggers hypersensitivity reaction (aka mucocutaneous lymph node syndrome)-INFANTS/YOUNG children-Skin rash, mucous membrane (mouth) lesions-Self limited, but 1-2% will die of coronary artery vasculitis
70
Microscopic Polyangitis...\*\*Clinical:
-\*\*RASH
71
Wegener Granulomatosis..Why may dentists see it?What else does it affect?Associated with presence of which antibodies?
-Involves sinuses/ upper airway---ALSO causes "strawberry gingivitis-lungs and kidney (glomerulonephritis)-PR3-ANCA
72
Thromboangiitis Obliterans (Buerger Disease)...Endothelial injury from:Usually begins before age ___ and causes pain and ischemia in \_\_\_\_
A substance in cigarette smokeBefore 45Extremities
73
\*\*\*\*Dissecting Aorta Hematoma (ANEURYSM)...How does it affect the media?Altered balance of collagen \_\_\_\_and \_\_\_\_Predisposing factors:Type A dissection is when you affect ______ which causes:Does it cause branch obstruction?
-Splits the media-Collagen synthesis and degradation -hypertension, CT disorders (Marfan).-Ascending aorta --\> sudden death-Yes, causes branch obstruction
74
What are the 2 ANCA - positive forms of vasculitis?
Wegener's and microscopic polyarteritis
75
Leukemias are malignant proliferations of cells native to the _____ which often spillover into the \_\_\_. They can spread to involve \_\_\_\_
bone marrowbloodorgans (usually liver and spleen..but also gingiva)
76
What is defined by Reed-Sternberg cells
Hodgkin Lymphoma
77
Hodgkin lymphoma....-Cause-Defined by:-It's characterized by spread within lymph node groups which is why ___ is important in assessing prognosisFever?Age:Prevalence:Difference of A and B (which has better prog)
-Possibly EBV-Reed-Sternberg cells-Staging-YES fever-Bimodal age distribution (15-30 / 50+)-Only 9,000... (NON-hodkins is 72,000)-A=absence of symptoms(better prog) B=presence of symptoms
78
NON-hodgkin lymphoma....Can be IN lymph nodes OR lymph tissue of solid organs.. basically ALL parts of the body!!!-Prognosis is based on:-Majority is of \_-cell origin -Classification of worst prognosis:-Classification of best prognosis:
-Grading/subtype (based on their morphology)-b cell origin-worst = LARGE DIFFUSE -small nodular
79
Hodgkin VS NHL...Which has RS cellsUsually has multiple node involvement:More common:Which is based on STAGE (location):Which is based on GRADING (morphology):Which affects ALL ages:Large painless lymph nodes:
RS = HodgkinMultiple node = NHLMore common = NHLStage = HodgkinGrading = NHLAll ages = NHLLarge painless nodes = BOTH
80
Biggest difference between acute and chronic Leukemias (with regards to bone marrow)
Acute has an increase in blasts (chronic doesn't have an increase in blasts)
81
Acute Lymphoblastic Leukemia (ALL)...\*\*\*The principal cause of cancer deaths for what age group:Affects which cells (B/T):Best prognosis group:
-\*\*\*\*Children-BOTH (B and T)-Children 2-1- with B cell type
82
Acute Lympoblastic Leukemia (ALL) vs Acute Myeloblastic Leukemia (AML)-Enlargement of lymph nodes, liver and spleen more common in:-Often involves CNS:-Which affects mostly children..which affects mostly adults-Remission more common with
-Enlargement more common = ALL-CNS = ALL-Children = ALL-Adults = AML-Remission = AML
83
Acute Myeloblastic Leukemia (AML)...-\*\*\*\*\*Marker for AML:-\*\*\*Cytoplasmic inclusions called _______ are diagnostic of AML-Usually affects what age
-Marker = myeloperoxidase-AUER RODS-Age = Older population
84
Chronic Lymphocytic Leukemia (CLL)...-\*\*\*\*\*Most common age group:Median survival:
-\>60 (OLDER ADULTS)\*\*\*-4-6yrs
85
Chronic Myelogenous Leukemia (CML)...The specific chromosomal abnormality is the _______ which results in fusion of the _____ genes.-What is almost always enlarged in CML patients?-Terminal phase is marked by increase of ___ in peripheral blood and marrow.-Decreased response to treatment is called:
-\*\*\*Philadelphia Chromosome- BCR-ABL genes-Enlargement of spleen-immature cells-blast crisis
86
What are the 2 main clinical features of Leukemia?
1) impairment of marrow function2 )infiltration of body organs
87
In plasma cell disorders, the secreted immunoglobulin results in increases of \_\_\_\_\_\_\_\_, which may have adverse effects on ___ and ___ fucntion
-increase of serum monoclonal protein (M component)-Adverse effects on renal and neurologic function
88
Multiple Myeloma...-Proliferating cell is a plasma cell that produces:-Most common immunoglobulin:-When only ____ chains are produced, patients can excrete them in the urine (aka \_\_\_\_\_\_\_)-Patients often present with:-What is the diagnostic characteristic?-Cure?-Life expectancy:
Immunoglobulin-IgG-Light chains ... Bence Jones proteinuria-Bone pain, hypercalcemia, renal disease-MULTIPLE bone lesions-No real cure (but some success with thalidomide and ant-resorptive tx.)-4-6yrs
89
Do testing for anemia DIRECTLY measure the red cell mass?Whats an INCREASE in red cell mass called?
NO! just reflectPolycythemia
90
RBC loss // Decreased RBC survival // or Decreased RBC production...\*\*\*Nutritional deficiency:Hemorrhage:Hemolysis (transplant not doing well):Malaria:Iron anemia:Hemolytic anemia:
Nutritional = decreased PRODUCTIONHemorrhage = lossHemolysis (transplant) = decreased survivalMalaria = decreased survivalIron anemia = decreased productionHemolytic anemia = decreased survival
91
Coomb's test is an autoimmune test to see if there is:
immunoglobulin on blood cells
92
Young healthy subjects can tolerate rapid blood loss of \_\_\_\_ml (\_\_% of total).Interstitial fluid will redistribute within \_\_\_Rapid blood loss of \_\_\_\_ml produces shock
500-1000ml (15-20%)24 hrs2000ml
93
The loss of RBC stimulates increased production, mediated by \_\_\_\_, resulting in an increase in the ____ count in the peripheral blood
mediated by erythropoietinincrease in the reticulocyte count
94
Chronic blood loss causes anemia when:
loss exceeds regeneration OR when iron reserves are depleted
95
INTRAvascular hemolysis...key feature:What is excreted in the urine?Conversion of heme to bilirubin leads to:Levels of ____ are characteristically low
-Key: decrease in serum haptoglobin-urine: free hemoglobin (hemoglobinuria)-bilirubin: hyperbilirubinemia and jaundice-heptoglobin
96
Which releases hemoglobin directly in blood and urine (hemoglobinuria).... Intra or Extravascular hemolysis
INTRAvascular hemolysis
97
EXTRAvascular hemolysis...-destruction of RBC in ______ (the blood filters). Which causes these organs to (inc/dec) in size-Examples (diseases):-Chronic elevated levels of bilirubin can promote formation of:
-spleen and liver (reticuloendothelial system)---spleen/liver increase in size-Sickle cell anemia, erythroblastosis fetalis (newborn hemolytic disorder)-formation of gallstones
98
Which are usually inherited? Which are normally acquired (intrinsic/extrinsic hemolytic anemia)
Intrinsic = inheritedExtrinsic = acquired
99
Hereditary spherocytosis....It's a defect of ___ which is a ____ protein of the cytoskeleton.Therapy: (and what can be a negative affect of therapy)Following splenectomy, production of ____ continues, but they're less destructive
-Defect of spectrin (a structural protein)-Removal of spleen (without spleen, you can get sepsis) -Spherocytes
100
Sickle Cell anemia-Inherited autosomal \_\_\_\_\_-Under ______ conditions, the abnormal hemoglobin polymerizes causing RBC to sickle-Complications include auto\_\_\_\_ (complete necrosis of this organ)-Heterozygotes have a resistance to which disease:
-Codominant-Low oxygen-autoSplenectomy-malaria
101
Thalassemia-Cell appearance:-What does it do in regards to bone marrow:-Principal clinical manifestation:-In almost all cases, there is a moderate to marked ____ with target cells... and ______ of the RBCs present on the blood smear.-Thalassemia is common in people from:-What does this reduce the impact of?
-pale and small -can causes bone marrow to be in places it usually isn't (like jaw)-Anemia (decreased hemoglobin production)-microcytosis (small appearance)-basophilic stippling of the RBCs-Mediterranean, african.-reduced malaria
102
G6DP deficiency-\*\*Morphologic hallmark:-Since G6DP is an antioxidant, RBCs are susceptible to:-Effect on RBC membrane:
-"Bite" cell-oxidative injury-membrane flexibility reduced
103
-Erythroblastosis fetalis is caused by:
-caused by blood group incompatibility between mother and fetus
104
Hemolytic Transfusion Reaction...Transfusion of incompatible RBCs results in activation of:Which antigens usually produce this activation?
-Activation of coagulation cascade with bleeding, renal failure, and shock.-ABO antigens
105
Autoimmune Hemolysis \*\*Hallmark?What is the cause?Coomb's test (pos/neg)
-\*\*Spherocytes-Patient makes antibodies to his own RBCs-Positive
106
Cardiac Valve Prosthesis.Hallmark of this mechanical trauma?
-schistocytes (loss of large portion of membrane)
107
Malaria..Parasites infect RBS and cause lysis of RBC during \_\_\_\_
maturation
108
What is the most common cause of anemia in the world?RBCs appearance:Important to recognize anemia may be a sign of a more serious disorder associated w/ chronic blood loss (ie \_\_\_\_\_)
iron deficiency -pale and white-cancer
109
Megaloblastic anemia is deficiency of:They are both involved w/ synthesis of:End result is abnormally \_\_\_RBC precursor, _____ production of MATURE RBCs, and abnormally large \_\_\_\_cells.
B12 and folate-thymidine-abnormally large RBC precursor (megaloblast), -decreased production of MATURE RBCs-also large white cells
110
Where is B12 found?Body stores? (large or small)Folate is found?Body stores?
B12: animal foodsStores: largeFolate: vegetablesStores: small
111
Px with pernicious anemia have autoantibodies directed against\_\_\_\_, which is a carrier for ___ so this causes ___ deficiency.B12 deficiency also causes a _____ disorderHow does this show on tongue?
-directed against intrinsic factor-carrier for B12-B12 deficiency-Demyelinating disorder (neurological....like gate probs)-Redness on tongue
112
What's it called when production of all cellular elements of the blood (red, white, platelets) are decreased.Over half the cases have no know cause (idiopathic)2 major path theories :Therapy?
Aplastic anemia1) acquired defect in stem cell production2) suppression of stem cells by T lymphocytes-Bone marrow transpant
113
What's it called when a tumor replaces bone marrow (so there isn't as much marrow to produce RBCs)
Myelophthisic anemia
114
When you run a marathon (dehydrated) , what happens in regards to RBCs?Living in a high altitude can produce:Neoplastic proliferation of myeloid cells is called:
Relative polycythemia (increase in RBC)secondary absolute polycythemia-polycythemia vera
115
Hemostasis definition:3 major components of hemostasis
ability to maintain blood in a fluid state AND prevent loss from sites of damage (hence "stasis"... equilibrium)-vascular wall, platelets, coagulation proteins
116
Primary hemostasis is \_\_\_drivenSecondary hemostasis is \_\_\_driven
Primary = plateletSecondary = coagulation (thrombin/fibrin)
117
During primary hemostasis, platelet adhesion involves activation of:What's the surface it adheres to?What mediates the adherence of platelets?
-surface membrane receptor (glycoprotein Ib)-subendothelial matrix (collagen)-vWF mediates adherence
118
Activation of primary hemostasis....Secretion:Activation of:Shape change:
Secretes: alpha granules-activation of GP IIb/IIIa receptor-from discoid to spherical
119
Aggregation of primary hemostasis...dependent on:Platelet-platelt binding mediated by:
calcium-fibrinogen
120
What does thrombin do (secondary hemostasis).What does it do to the clot?
Converts fibrinogen to fibrin -Adds stability to the clot
121
Which pathway is more important in secondary hemostasis?It's activated by:
EXTRINSIC -tissue factor
122
Antithrombins def:
inhibit activity of thrombin and other serine proteases
123
What is the protein C system?What's the major effector enzyme, what's the major cofactor?Deficiencies in this system would cause:What does Factor V Ledin mutation promote?
REGULATES hemostasis (they slow down hemostasis)-Protein C is the major effector enzyme, protein s is a major cofactorHypercoagulability-Coagulation
124
Summary of REGULATION of coagulation...Antithrombin inhibits:Protein c inhibits:Plasmin breaks down:
Antithrombin inhbits serine proteasesProtein C inhibits cofactorsPlasmin breaks down fibrin clot
125
Screening tests to evaluate hemostasis...Prothrombin Time def:\*\*\*Used to initiate ____ coagulation cascade
time needed for plasma to form a clot in the presence of added tissue thromboplastinEXTRINSIC
126
Screening tests to evaluate hemostasis...Partial Thromboplastin TimeMeasurement of ____ pathway
time needed for plasma to form a clot in the presence of added ground glass or kaolin (to activate factor XII)INTRINSIC
127
When either the PT or PTT is prolonged, a ______ with 1:1 ratio of normal plasma:patient plasma is performed.If mixing study corrects clotting time, px has ____ of factors.If the mixing times does NOT correct the clotting time, an \_\_\_\_is present (either ____ or \_\_\_\_\_type)
mixed studydeficiency of factorsinhibitor (factor-specific or lupus anticoagulant type)
128
If bleeding disorder screening laboratory tests are normal, disorder of the ____ system may be suspected
regulatory
129
Disorders of Primary or Secondary hemostasisWhich causes more superficial bleeding (i.e. mucosa)?Which causes deeper bleeding (i.e. joints)?
Primary = superficialSecondary = deeper
130
vWF functions both as the carrier molecule for ______ and as the "glue" between damaged endothelium and platelets (primary hemostasis)
Factor VIII
131
What is the most common inherited bleeding disorder?
von Willebrand disease (1% of population)
132
von Willebrand disease predominant clinical manifestation:Symptoms often improve after (what age group):Bleeding time? PTT?Therapy:
mucocutaneous bleeding (nosebleeds - epistaxis, bruise - ecchymoses)-adolescence-prolonged bleeding time, prolonged PTT-desmopressin, factor VIII, cryoprecipitate
133
Hemophilia A is a ________ recessive disorder due to decreased production of \_\_\_\_-Most common cause for:-Clinical hallmark:-Bleeding time? PTT? Factor VIII-Severe hemo A is characterized by:-Therapy:-Complications:
sex-lined recessive (affects males)-decreased production of Factor VIII-serious bleeding-recurrent soft tissue bleeding-normal bleeding time, prolonged PTT, decreased VIII-\<1% Factor VIII-Replacement of Factor VIII-joint disease, pseudotumors (hematomas)
134
How is Hemophilia B different than A?How is vWF disease different than Hemo A
Decreased production of Factor IX (instead of VIII in A)vWF has mucocutaneous bleeding
135
Decrease in platelet count is called:Bleeding due to thrombocytopenia typically appears as:Evaluation of thrombocytopenia is made using peripheral \_\_\_\_\_\_\_, or \_\_\_\_
thrombocytopenia-petechial hemorrhages in skin and mucous membranes-blood smear, bone marrow exam to determine if platelet are being produced in adequate numbers
136
What disorder is characterized by immune-mediated destruction of platelets?-Acute form occurs in (what age)-Therapy:-What group of people predominate-Therapy:
Immune Thrombocytopenic Purpura (ITP)Childhood-Self limited (2-6 weeks)-Females w/ autoimmune disorders predominate-corticosteriods, IV immunoglobulin, splenectomy
137
Cause of Thrombotic Thrombocytopenic Pupura (TTP):Deficiency of this enzyme results in:Left untreated:
-deficiency of of metalloproteinase (ADAMTS 13), that normally degrades some vWF.-abnormally large vWF in the plasma.-death (renal failure)
138
Disseminated Intravascular Coagulation (DIC) results from:There is both formation of ___ and \_\_\_.Coagulation factors are activated and consumed faster than they can be \_\_\_\_. Resulting in:Clinical manifestation:Sepsis increases risk of DIC.Therapy:
uncontrolled activation of the hemostatic system.-formation of thrombin and plasmin-produced; bleeding and microvascular thrombi-bleeding from multiple sites-Directed at removing the initating stimulus, and supporting that patient's coagulation protein reserve w. transfusions of plasma and platelets
139
Azotemia def:Uremia def:
RENAL DISEASESAzotemia = elevation of blood urea nitrogen (BUN) and creatinine levels, due to decreased GFRUremia = azotemia + other clinical symptoms
140
Acute Nephritic Syndrome \*\*\*characterized by:Nephrotic syndrome is characterized by: (how many grams per day)Acute renal failure:
Nephritic = \*\*HEMATURIANephrotic = Proteinuria (\>3.5g per day)Renal failure: acute onset of azotemia w/ oliguria
141
Autosomal dominant vs recessive polycystic kidney disease....-In adults:-Kids:-Which is more common (1:500-1000):-Gradual onset:-\*\*\*Creates cysts in Circle of Willis (intracranial):-Has the gene mutation that includes liver (pkHd1..H is hepatic):-Causes very large kidneys:-Cysts arise from collecting tubules
-Adults = dominant-Kids = recessive-More common = dominant-Gradual = dominant (hence adults)-\*\*Intracranial cysts = dominant-PKHD1 = recessive-Large kidneys = dominant-Collecting Tubules = recessive
142
What are the 2 mechanisms of Glomerular Injury:
1. Immune complex deposits in Glomerular Basement Membrane (GBM)2. Epithelial and endothelial injury
143
For evaluation of kidney biopsies, you use EM (electron microscopy) to identify:
More specific location of beasement membrane
144
Nephrotic syndrome findings...LM:IF:EM:
LM: normalIF: no immune complexe EM: foot process effacment
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Minimal Change Disease...-Path in EM:-Most common cause of Nephrotic syndrome in \_\_\_\_\_.-Response to treatment (good/bad)
-Epithelial cell foot processes-Most common of = children-Treatment = good
146
Focal and segmental glomeruloslerosis...-Sub category of _____ syndrome.-Characterized by:-Response to treatment:
-Nephrotic syndrome-Increased mesangial matrix collagen with obliteration of capillary loops -Poor response to tx.
147
Membranous Nephropathy (glomerulonephritis)-Sub category of _____ syndrome.-Most common in what age:-\*\*Pathology:-Response to tx.
-Nephrotic syndrome-Adults 30-50-Path: Immune complexes in the EPITHELIAL side (SUBEPITHELIAL)-Poor response to tx.
148
What is the 2nd most common cause of death from diabetes (after MI).What is the characteristic of renal disease w/ diabetes:
Renal failure.-Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)
149
Nephritic syndrome...Inflammation severely injures \_\_\_\_\_\_Acute postinfectious (poststreptococcal) glomerulonephritis is associated w/ _____ cells.IgA Nephropathy causes _____ after \*\*upper respiratory infection\*\*Manifestation:\*\*Pathology:
-Capillary walls\*\*-Inflammatory cells (neutrophils and monocytes)-Hematuria-Skin rash and arthritis (Henoch-Schonlein purpura)-\*\*Path: mesangial deposition of immune complexes
150
3 things that kidney disease will affect:
GlomeruliRenal VeinsRenal Pelvis
151
Rapidly Progressive Glomerulonephritis is progressive loss of:-Characteristic finding:Manifestation:
-Loss of renal function-Crescents-Severe oliguria (inability to produce urine)
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Chronic (end -stage) renal disease is loss of glomeruli and tubules leads to \_\_\_\_\_. Damaged glomeruli become completely \_\_\_\_.
FibrosisSclerotic
153
Acute Pyelonephritis is usually caused by:What direction does this infection spread?\*\*What lodges in kidney walls?Treatment?
-bacterial infection-ascends (from bladder to kidney)-\*\*neutrophils (inflammation!)-treat bacterial infection
154
Drug-induced Interstitial Nephritis...RAPID onset of:Path:
fevereosinophils
155
Acute Tubular Necrosis characteristic: (can it regenerate?)Affect on urine:How does it affect the glomerulus?Most common etiology?
-Tubular damage (Which CAN regenerate)-Oliguria (T affect glomerulus-Most common = ischemia
156
Arterionephrosclerosis is associated w/:What group of people does it affect?Effect on kidneys:Pathology:
benign hypertension-African Americans-very small kidneys (cuz they don't get enough blood)-HYPERPLASTIC areriosclerosis
157
Thrombotic Thrombocytopenia Purpura (TTP) AND Hemolytic-Uremic Syndrome (HUS) are related to activation, aggregation, and consumption of:Which one affects kidney?Which one affects more organs?
plataletsTTP= all organs (including CNS)HUS= just kidney
158
Why is ground beef usually recalled? (SHIGA TOXIN)
HUS
159
WHo is at high risk for kidney stones because of high cell turnover?
Ppl with Leukemia
160
Renal Cell Carcinoma...Age group/gender:Predisposing factor:Clinical:This carcinoma is an exception because it invades:
-Older males-polycystic disease due to chronic dialysis -polycythemia (increased RBC) -renal vein (usually lymph)
161
Wilm's tumor is one of the most common cancers in ____ (age).\*\*\*Pathology:
-Children (2-5yrs)-Triphasic proliferation (epithelial, stromal, BLASTEMAL)
162
Glycoprotein IIb/IIIa on the _____ binds \_\_\_
on the PLATELETS binds FIBRINOGEN
163
Heparin works the same way as \_\_\_\_. Which works by stopping:
antithrombinstopping thrombin from making fibrin (inhibit serine proteases)
