Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
271 Cards in this Set
- Front
- Back
|
where is the majority of extracellular fluid found?
|
interstitium (third space) that lies between cells
|
|
|
about what percent of total body water is in the blood plasma?
|
5%
|
|
|
where do lymphatic vessels ultimately return to the blood stream?
|
thoracic duct
|
|
|
what two factors can result in increased interstitial fluid?
|
increased capillary pressure
diminished colloid osmotic pressure |
|
|
what is an abnormal increase in interstitial fluid within tissues called?
|
edema
|
|
|
what are the names for the abnormal increases in different body cavities?
|
hydrothorax
hydropericardium hydroperitoneum (ascites) |
|
|
what is anasarca?
|
severe, generalized edema with widespread subcutaneous tissue swelling
|
|
|
what type of fluid is edema caused by increased hydrostatic pressure or reduced plasma protein?
|
transudate
protein poor |
|
|
in what conditions is transudate seen?
|
congestive heart failure
renal failure hepatic failure malnutrition |
|
|
what type of fluid is edema caused by increased vascular permeability?
|
exudate
protein rich (commonly seen in inflammation) |
|
|
what is the result of a focal impairment in venous return?
|
regional increases in hydrostatic pressure, with resulting localized edema
e.g. deep venous thrombosis |
|
|
what is the result of congestive heart failure?
|
generalized increases in venous pressure, with resulting systemic edema
|
|
|
what is the major plasma protein?
|
albumin
|
|
|
when does reduced plasma osmotic pressure occur?
|
when albumin, the major plasma protein, is not synthesized in adequate amounts or is lost from circulation
|
|
|
what is nephrotic syndrome?
|
a group of symptoms including protein in the urine (more than 3.5 grams per day), low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling, caused because glomerular capillaries become leaky
patients typically present with generalized edema b/c of loss of proteins via kidneys |
|
|
what are the effects of excess sodium and subsequent water retention?
|
increased hydrostatic pressure, b/c of intravascular fluid volume expansion
decreased vascular colloid osmotic pressure, b/c of dilution of concentration of proteins |
|
|
when does salt retention occur?
|
whenever renal function is compromised
- primary disorders of the kidney - disorders that decrease renal perfusion |
|
|
what is the effect of congestive heart failure on the kidneys?
|
hypoperfusion
|
|
|
what is the effect of hypoperfusion on the kidneys?
|
stimulates the renin-angiotensin-aldosterone system, to retain sodium and water
beneficial at first b/c it helps to improve CO and restore normal renal perfusion as the patient's condition worsens, the retained fluid merely increases the venous pressure and causes edema |
|
|
what are the valuable treatments for generalized edema?
|
salt restriction
diuretics aldosterone antagonists |
|
|
where is ADH released from?
|
posterior pituitary gland
|
|
|
what are the effects of ADH?
|
primary retention of water
modest vasoconstriction |
|
|
under what conditions is ADH normally released?
|
reduced plasma volumes
increased plasma osmolarity |
|
|
in what disorders can an inappropriate increase in ADH be seen? what are the results of this?
|
malignancies, lung and pituitary disorders
hyponatremia and cerebral edema (not peripheral edema) |
|
|
what is the result of impaired lymphatic drainage?
|
lymphedema (typically localized)
|
|
|
what are the causes of lymphedema?
|
chronic inflammation with fibrosis
invasive malignant tumors physical disruption radiation damage certain infectious agents (e.g. filarriasis) |
|
|
what is filariasis?
|
a parasitic disease and is considered an infectious tropical disease, that is caused by thread-like filarial nematodes (roundworms)
causes lymphatic obstruction in the inguinal lymphatic and lymph nodes, via fibrosis, and subsequently causes elephantiasis |
|
|
what is a common complication of surgical removal and/or irradiation of the breast and associated axillary lymph nodes in patients with breast cancer?
|
severe edema of the upper extremity
|
|
|
how does edema appear microscopically?
|
clearing and separation of the extracellular matrix and subtle cell swelling
|
|
|
where is edema most commonly seen?
|
can be seen in any organ or tissue, but most commonly in subcutaneous tissues, lungs, and brain
|
|
|
what is dependent edema?
|
swelling in lower, or gravity-dependent, parts of the body
(legs when standing, sacrum when recumbent) |
|
|
what is pitting edema?
|
swelling in which pressure leaves a persistent depression in the tissues, even after removed
(pressing on the edematous subcutaneous tissue displaces the intersitial fluid, and leaves a depression) |
|
|
what is periorbital edema?
|
swelling in the loose connective tissue matrix of the eyelids
characteristic finding in severe renal disease |
|
|
describe pulmonary edema
|
the lungs are often 2-3 times their normal weight, and sectioning yields frothy, blood-tinged fluid (mixture of air, edema, and extravasated red blood cells
|
|
|
how does the brain appear with generalized edema?
|
it is grossly swollen with narrowed sulci and distended gyri (evidence of compression against the unyielding skull
|
|
|
why is subcutaneous tissue edema important?
|
signals potential underlying cardiac or renal disease
can also impair wound healing or the clearance of infection if severe |
|
|
in what clinical setting is pulmonary edema typically seen?
|
left ventricular failure
renal failure acute respiratory distress syndrome pulmonary inflammation pulmonary infection |
|
|
what are the effects of pulmonary edema?
|
collects in the alveolar septa around capillaries and impedes oxygen diffusion
edema fluid in the alveolar spaces creates a favorable environment for bacterial infection |
|
|
from what do both hyperemia and congestion stem?
|
locally increased blood volumes
|
|
|
what is hyperemia?
|
an active process in which arteriolar dilation leads to increased blood flow
|
|
|
why do hyperemic tissues become erythematous?
|
because of the engorgement of vessels with oxygenated blood
(e.g. sites of inflammation or in skeletal muscle during exercise) |
|
|
what is congestion?
|
passive process resulting from reduced outflow of blood from a tissue
|
|
|
why do congested tissues take on a dusky reddish-blue (cyanotic) color?
|
red blood cell stasis and accumulation of deoxygenated hemoglobin
|
|
|
what can cause small hemorrhagic foci in chronic congestion?
|
capillary rupture
subsequent catabolism of extravasated red cells can leave residual clusters of hemosiderin-laden macrophages |
|
|
what are heart failure cells?
|
hemosiderin-laden macrophages created by catabolism of extravasated red blood cells
telltale sign of chronic congestion |
|
|
describe what is seen in acute hepatic congestion
|
the central vein and sinusoids are distended; centrilobular hepatocytes can be ischemic while periportal hepatocytes - better oxygenated b/c of proximity to hepatic arterioles - may only develop fatty change
|
|
|
describe what is seen in chronic passive hepatic congestion
|
centrilobular regions are grossly red-brown and slightly depressed (b/c of cell death) and are accentuated against the surrounding zones of uncongested tan liver (nutmeg liver)
|
|
|
what is nutmeg liver?
|
aka chronic passive hepatic congestion
liver dysfunction due to venous congestion, usually cardiac dysfunction, i.e. right heart failure or (less specifically) congestive heart failure |
|
|
define hemorrhage
|
extravasation of blood into the extravascular space
|
|
|
define hemorrhagic diathesis
|
unusual susceptibility to bleeding (hemorrhage) mostly due to hypocoagulability, in turn caused by a coagulopathy (a defect in the system of coagulation)
|
|
|
what is a hematoma?
|
localized collection of blood outside the blood vessels, usually in liquid form within the tissue
|
|
|
what are petechiae?
|
minute 1- to 2-mm hemorrhages into skin, mucous membranes, or serosal surfaces
|
|
|
with what are petechiae commonly associated?
|
increase in intravascular pressure
low platelet counts defective platelet function |
|
|
what is thrombocytopenia?
|
low platelet counts
|
|
|
what are purpura?
|
small hemorrhages (>3mm), slightly larger than petechiae, into skin, mucous membrane, or serosal surfaces
|
|
|
what are ecchymoses?
|
larger (>1-2cm) subcutaneous hematomas (i.e. bruises)
|
|
|
what are the causes of purpura?
|
locally increased intravascular pressure
low platelet counts defective platelet function secondary to trauma vascular inflammation increased vascular fragility |
|
|
what is the process by which hemoglobin is degraded?
|
hemoglobin (red-blue color)
-> bilirubin (blue-green color) -> hemosiderin (gold-brown color) |
|
|
at what point do hemorrhages become significant?
|
rapid loss of up to 20% of the blood volume or slow losses of even larger amounts may have little impact in healthy adults
|
|
|
what type of shock is hemorrhagic shock?
|
hypovolemic shock
|
|
|
what is the effect of chronic or recurrent blood loss (e.g. peptic ulcer or menstrual bleeding)?
|
net loss in iron and can lead to an iron deficiency anemia
|
|
|
what is thrombosis?
|
blood clot (thrombus) formation within intact vessels
|
|
|
what are the three components of both hemostasis and thrombosis?
|
vascular wall (endothelium)
platelets coagulation cascade |
|
|
what happens to the arterioles initially after an injury?
|
brief period of arteriolar vasoconstriction mediated by reflex neurogenic mechanisms and augmented by the local secretion of endothelin
|
|
|
what is endothelin?
|
potent endothelium-derived vasoconstrictor
(important in vasoconstriction immediately following injury) |
|
|
what facilitates platelet adherence and activation in endothelial injury?
|
exposure of highly thrombogenic subendothelial extracellular matrix
|
|
|
what is the conformational change in platelets seen when they are activated?
|
from small rounded discs to flat plates with markedly increased surface area
|
|
|
what two changes occur in platelets when they are activated by extracellular matrix?
|
dramatic shape change
release of secretory granules |
|
|
what is aggregation?
|
secreted products of platelets recruits additional platelets to form a hemostatic plug
|
|
|
what process is referred to as primary hemostasis?
|
formation of a hemostatic plug from aggregation of platelets
|
|
|
what is factor III?
|
aka tissue factor
aka thromboplastin membrane-bound procoagulant glycoprotein synthesized by endothelial cells |
|
|
what two factors act in conjunction as the major in vivo initiators of the coagulation cascade?
|
factor III (tissue factor)
factor VII (proconvertin) |
|
|
what enzyme cleaves circulating fibrinogen into fibrin, creating a fibrin meshwork?
|
thrombin
|
|
|
what is secondary hemostasis?
|
the formation of fibrin (and a fibrin meshwork) through the coagulation cascade
|
|
|
what are the antithrombotic effects of normal endothelial cells?
|
antiplatelet effects
anticoagulant effects fibrinolytic effects |
|
|
how do normal endothelial cells exhibit antiplatelet effects?
|
- nonactivated platelets do not adhere
- adhesion of activated platelets is impeded by prostacyclin and nitric oxide produced by endothelial cells - endothelial cells produce adenosine diphosphatase, which degrades ADP and inhibits platelet aggregation |
|
|
what mediators are produced by normal endothelial cells to impede the adherence and aggregation of platelets?
|
prostacyclin (PGI2)
nitric oxide (NO) |
|
|
what enzyme is produced by normal endothelial cells to impede the adherence and aggregation of platelets?
|
adenosine diphosphatase
degrades ADP; since ADP activates platelets to aggregate, adenosine diphosphatase inhibits platelet aggregation |
|
|
how are the anticoagulant effects of normal endothelial cells mediated?
|
1) endothelial membrane-associated heparin-like molecules
2) thrombomodulin 3) tissue factor pathway inhibitor |
|
|
how do endothelial membrane-associated heparin-like molecules exert anticoagulant effects?
|
indirectly
greatly enhance inactivation of thrombin via antithrombin III |
|
|
how does thrombomodulin exert anticoagulant effects?
|
binds to thrombin and converts it from a procoagulant into an anti coagulant via its ability to activate protein C (which inactivates factors Va and VIIIa)
|
|
|
what is tissue factor pathway inhibitor?
|
cell surface protein that directly inhibits tissue factor-factor VIIa and factor Xa activities
|
|
|
what are the prothrombotic properties induced in endothelial cells by inflammation?
|
platelet effects
procoagulant effects antifibrinolytic effects |
|
|
through what product of normal endothelial cells is platelet adhesion mediated?
|
von Willebrand factor (vWF)
|
|
|
what are the procoagulant effects of endothelial cells, activated by inflammation?
|
synthesize tissue factor (major activator of the extrinsic clotting cascade)
augment the catalytic function of activated coagulation factors IXa and Xa |
|
|
what is the major activator of the extrinsic clotting cascade?
|
tissue factor (factor III)
|
|
|
what are the antifibrinolytic effects of endothelial cells activated by inflammation?
|
secrete inhibitors of plasminogen activator (PAIs), which limit fibrinolysis and favor thrombosis
|
|
|
what are platelets?
|
disc-shaped, anucleate cell fragments shed from megakaryocytes in the bone marrow
|
|
|
what is contained in alpha granules of platelets?
|
P-selectin on the membrane
fibrinogen fibronectin factor V factor VIII (anti-hemophillic factor) platelet factor 4 platelet-derived growth factor transforming growth factor-beta |
|
|
what is contained in dense granules of platelets?
|
ADP
ATP ionized calcium histamine serotonin (5-HT) epinephrine |
|
|
to what receptor on platelets does von Willebrand factor bind?
|
GpIb
|
|
|
what two things does von Willebrand factor connect?
|
collagen in the extracellular matrix
GpIb receptor on platelets |
|
|
for what are the interactions between von Willebrand factor and the GpIb receptor important?
|
necessary to overcome the high shear forces of flowing blood
|
|
|
what is deficient in von Willebrand disease?
|
von Willebrand factor (vWF)
|
|
|
what is deficient in Bernard-Soulier syndrome?
|
GpIb receptor
(receptor for vWF on platelets) |
|
|
why is the release of contents from dense-bodies of platelets especially important to coagulation?
|
calcium is required in the coagulation cascade
ADP is a potent activator of platelet aggregation |
|
|
what causes negatively charged phospholipids (esp. phosphatidylserine) to appear on the surfaces of platelets?
|
platelet activation
|
|
|
what is the function of negatively charged phospholipids (esp. phosphatidylserine) on the surfaces of platelets?
|
bind calcium and serve as critical nucleation sites for the assembly of complexes containing the various coagulation factors
|
|
|
besides ADP, what is the other important platelet-derived stimulus that amplifies platelet aggregation, leading to the primary hemostatic plug?
|
thromboxane A2 (TxA2)
|
|
|
how does thrombin stabilize the platelet plug?
|
binds to a protease-activated receptor (PAR) on the platelet membrane and in concert with ADP and TxA2 causes further platelet aggregation; followed by platelet contraction, this creates an irreversibly fused mass of platelets
converts fibrinogen to fibrin in the vicinity of the platelet plug, functionally cementing the platelets into place |
|
|
what does platelet contraction depend on?
what is its effect? |
depends on the platelet cytoskeleton
creates an irreversibly fused mass of platelets |
|
|
what is the function of fibrin?
|
to functionally cement platelets into place in the secondary hemostatic plug
|
|
|
what enzyme converts fibrinogen into fibrin?
|
thrombin
|
|
|
what triggers a conformational change in the platelet GpIIb-IIIa receptor that induces binding to fibrinogen?
|
platelet activation by ADP
|
|
|
what is deficient in Glanzmann thrombasthenia?
|
GpIIb-IIIa
|
|
|
why is noncleaved fibrinogen important?
|
important for platelet aggregation, because it binds the GpIIb-IIIa receptor on platelets and forms bridging interactions between platelets that promote platelet aggregation
|
|
|
to what platelet receptor does noncleaved fibrinogen bind?
|
GpIIb-IIIa
forms bridges between activated platelets |
|
|
what binds to the platelet GpIIb-IIIa receptor?
|
noncleaved fibrinogen
forms bridges between activated platelets |
|
|
how do leukocytes adhere to platelets?
|
P-selectin
|
|
|
what is the clinical utility of aspirin in patients at risk of coronary thrombosis?
|
aspirin is an irreversible cyclooxygenase inhibitor
it permanently blocks platelet TxA2 synthesis although endothelial prostacyclin production is also inhibited by aspirin, endothelial cells can resynthesize active COX and thereby overcome the blockade, but platelets can't |
|
|
what factor stabilizes fibrin polymers?
|
factor XIIIa
|
|
|
what is factor XIIIa activated by?
|
thrombin
|
|
|
what is the effect of calcium chelators on coagulation?
|
prevents clotting of blood
|
|
|
on what are the components of coagulation factors typically assembled?
|
on a phospholipid surface
held together by calcium ions |
|
|
what coagulation factors are dependent on the addition of gamma-carboxyl groups to certain glutamic residues?
|
factors II, XII, IX, and X
|
|
|
what cofactor is required for the gamma-carboxylation of coagulation factors?
|
vitamin K
|
|
|
what drugs antagonize gamma-carboxylation of coagulation factors?
|
coumadin
|
|
|
at what coagulation factor do the extrinsic and intrinsic pathways of coagulation converge?
|
factor X
|
|
|
why was the extrinsic pathway so designated?
|
requires the addition of an exogenous trigger
|
|
|
what is required by the intrinsic factor for activation?
|
exposing factor XII (Hageman factor) to thrombogenic surfaces
|
|
|
what is the most physiologically relevant pathway for coagulation?
|
extrinsic pathway
occurs when vascular damage has occurred |
|
|
what are the two standard assays to assess the function of the two arms of the coagulation pathway?
|
prothrombin time (PT)
partial thromboplastin time (PTT) |
|
|
what assay assesses the function of enzymes in the extrinsic pathway?
|
prothrombin time (PT)
assesses factors VII, X, II, V, and fibrinogen |
|
|
what enzymes are assessed by the prothrombin time (PT) assay?
|
factors in the extrinsic pathway
assesses factors VII, X, II, V, and fibrinogen |
|
|
what enzymes activate XII to XIIa?
|
high molecular weight kininogen (HMWK)
|
|
|
what enzymes activate factor XI to factor XIa?
|
thrombin
XIIa |
|
|
what factor activates factor IX to factor IXa?
|
factor XIa
|
|
|
what factor activates factor VIII to factor VIIIa?
|
thrombin
|
|
|
what enzymes activate factor X to factor Xa?
|
factor IXa/VIIIa compound
factor VIIa/tissue factor compound |
|
|
what factor activates factor II to factor IIa?
|
factor Xa
|
|
|
what enzyme activates factor V to factor Va?
|
thrombin (factor II)
|
|
|
what factor activates factor XIII to factor XIIIa?
|
thrombin (factor II)
|
|
|
what are the steps of the intrinsic clotting pathway?
|
XII -> XIIa
XI -(XIIa / IIa)-> XIa IX -(XIa)-> IXa VIII -(IIa)-> VIIIa X -(IXa+VIIIa)-> Xa V -(IIa)-> Va II -(Va+Xa)-> IIa fibrinogen -(IIa)-> fibrin XIII -(IIa)-> XIIIa fibrin -(XIIIa)-> cross-linked fibrin |
|
|
what are the steps of the extrinsic clotting pathway?
|
tissue injury
-> tissue factor -(VII)->Tissue Factor+VIIa X -(tissue factor+VIIa)-> Xa V -(IIa)-> Va II -(Va+Xa)-> IIa fibrinogen -(IIa)-> fibrin XIII -(IIa)-> XIIIa fibrin -(XIIIa)-> cross-linked fibrin |
|
|
what assay screens for the function of intrinsic pathway enzymes?
|
partial thromboplastin time
assesses factors XII, XI, IX, VIII, X, V, II, and fibrinogen |
|
|
function of what enzymes is assayed by the partial thromboplastin time (PTT)?
|
enzymes in the intrinsic pathway
factors XII, XI, IX, VIII, X, V, II, and fibrinogen |
|
|
how are most of the proinflammatory effects of thrombin mediated?
|
activation of protease activated receptors (PARs)
|
|
|
where are PARs expressed?
|
PARs = protease activated receptors
expressed on endothelium, monocytes, dendritic cells, T lymphocytes, and other cell types |
|
|
how are PARs activated?
|
PARs = protease activated receptors
activation is initiated by cleavage of the extracellular end of the PAR; this generates a tethered peptide that binds to the clipped receptor |
|
|
what are the three categories of endogenous anticoagulants that control clotting?
|
1) antithrombins
2) Proteins C and S 3) tissue factor pathway inhibitor (TFPI) |
|
|
what is the function of antithrombins (e.g. antithrombin III)?
|
inhibit the activity of thrombin and other serine proteases (factors IXa, Xa, XIa, and XIIa)
activated by binding to heparin-like molecules on endothelial cells |
|
|
what is the function of Proteins C and S?
|
act in a complex that proteolytically inactivates factors Va and VIIIa
|
|
|
by what is protein C activated?
|
thrombomodulin
|
|
|
what is TFPI?
|
tissue factor pathway inhibitor
protein produced by endothelium that inactivates tissue factor-factor VIIa complexes |
|
|
through what enzyme is fibrinolysis mainly accomplished?
|
plasmin
breaks down fibrin and interferes with polymerization |
|
|
what is the role of fibrin split products in coagulation?
|
weak anticoagulants produced from plasmin-mediated cleavage of fibrin
|
|
|
what is the role of fibrin split products clinically?
|
elevated levels of fibrin split products (esp. fibrin-derived D-dimers) can be used to diagnose abnormal thrombotic states including disseminated intravascular coagulation (DIC), DVT, or pulmonary embolism
|
|
|
how is plasmin generated?
|
enzymatic catabolism of plasminogen (inactive precursor) by a factor XII-dependent pathway or by plasminogen activators
|
|
|
what is the most important plasminogen activator?
|
tissue plasminogen activator (t-PA)
|
|
|
where is t-PA synthesized?
|
principally by endothelium
|
|
|
when is t-PA most active?
|
when bound to fibrin
t-PA (tissue plasminogen activator) cleaves fibrin and degrades fibrin clots |
|
|
what is special about urokinase-like PA (u-PA)?
|
can activate plasmin in the fluid phase
|
|
|
what bacterial enzyme can cleave plasminogen to plasmin?
|
streptokinase
|
|
|
how is free plasmin rapidly inactivated?
|
alpha2-plasmin inhibitor
|
|
|
how does plasminogen activator inhibitor (PAI) block fibrinolysis?
|
inhibits t-PA binding to fibrin (convers an overall procoagulant effect)
|
|
|
what is Virchow's triad?
|
three primary abnormalities that lead to thrombus formation
1) endothelial injury 2) stasis or turbulent blood flow 3) hypercoagulability of the blood |
|
|
why is endothelial injury particularly important in thrombus formation in the heart or arterial circulation?
|
the normally high flow rates might otherwise impede clotting by preventing platelet adhesion and washing out activated coagulation factors
|
|
|
describe the normal laminar flow of blood through blood vessels
|
platelets and other bood cellular components flow centrally in the vessel lumen, separated from the endothelium by a slower moving layer of plasma
|
|
|
what are the effects of stasis and turbulence on the thrombotic capacity of the body?
|
promote endothelial activation, enhancing procoagulant activity, leukocyte adhesion, etc.
disrupt laminar flow and bring platelets into contact with endothelium prevent washout and dilution of activated clotting factors by fresh flowing blood, as well as the inflow of clotting factor inhibitors |
|
|
what results from rheumatic mitral valve stenosis?
|
left atrial dilation
|
|
|
in what condition is blood hyperviscosity seen?
|
polycythemia vera
|
|
|
what is the effect of hyperviscosity of the blood?
|
increases resistance to flow
causes small vessel stasis |
|
|
what is thrombophilia?
|
hypercoagulability
loosely defined as any alteration in the coagulation pathways that predisposes to thrombosis |
|
|
what are the two types of hypercoagulability disorders?
|
primary (genetic)
secondary (acquired) |
|
|
what are the most common inherited causes of hypercoagulability?
|
point mutations in the factor V gene and prothrombin gene
|
|
|
what is the Leiden mutation?
|
a single nucleotide mutation in coagulation factor V
results in a glutamine to arginine substitution at position 506 that renders factor V resistant to cleavage by protein C |
|
|
what is the deficiency in Factor V Leiden?
|
factor V cleavage by protein C is deficient because of a mutation in the factor V gene
|
|
|
what is the effect of the mutation in the prothrombin gene?
|
elevated prothrombin levels and an almost threefold increased risk of venous thromboses
|
|
|
what is the effect of homocysteine on coagulation?
|
elevated levels of homocysteine contribute to arterial and venous thrombosis, as well as the development of atherosclerosis
|
|
|
what causes the prothrombotic effects of homocysteine?
|
thioester linkages formed between homocysteine metabolites and a variety of proteins, including fibrinogen
|
|
|
if heterozygosity for Factor V Leiden or for prothrombin defect impart only moderately increased risk, why is it such a big problem?
|
mutations in factor V and prothrombin are frequent enough that homozygosity and compound heterozygosity are not rare, and such genotypes are associated with greater risk
|
|
|
what is the probable cause for hypercoagulability due to oral contraceptive use or the hyperestrogenic state of pregnancy?
|
increased hepatic synthesis of coagulation factors and reduced anticoagulant synthesis
|
|
|
what is HIT?
|
heparin-induced thrombocytopenia syndrome
following the administration of unfractionated heparin, antibodies appear that recognize complexes of heparin and platelet factor 4 on the surface of platelets binding of these antibodies to platelets results in their activation, aggregation, and consumption this effect on platelets and endothelial damage to create a prothrombotic state even in the face of heparin administration and low platelet counts |
|
|
what is the solution that has at least decreased the incidence of HIT?
|
HIT = heparin-induced thrombocytopenia syndrome
newer low-molecular weight heparin preparations induce antibody formation less frequently than unfractionated heparin, but still cause thrombosis if antibodies have already formed |
|
|
what are the clinical manifestations of antiphospholipid antibody syndrome?
|
recurrent thromboses
repeated miscarriages cardiac valve vegetations thrombocytopenia pulmonary embolism (following LE DVT) pulmonary hypertension stroke bowel infarction renovascular hypertension |
|
|
what causes the fetal loss in antiphospholipid antibody syndrome?
|
antibody-mediated inhibition of t-PA activity necessary for trophoblastic invasion of the uterus
|
|
|
how are the pathologic effects of antiphospholipid antibody syndrome mediated?
|
binding of antibodies to epitopes on plasma proteins (e.g. prothrombin) that are somehow induced or unveiled by phospholipids
|
|
|
why do antibodies from antiphospholipid antibody syndrome often give a false positive test for syphilis?
|
the antigen in the standard assay is embedded in cardiolipin
|
|
|
what patients are considered to have secondary antiphospholipid antibody syndrome?
|
those with clearly defined autoimmune disease, such as systemic lupus erythematosus
|
|
|
what patients are considered to have primary antiphospholipid antibody syndrome?
|
those that exhibit only the manifestations of a hypercoagulable state and lack evidence of other autoimmune disorders
|
|
|
what is catastrophic antiphospholipid syndrome?
|
particularly aggressive form of antiphospholipid syndrome characterized by widespread small-vessel thrombi and multi-organ failure (with 50% mortality)
|
|
|
where do arterial or cardiac thrombi typically originate? how do they grow?
|
sites of turbulence or endothelial injury
tend to grow retrograde from point of attachment |
|
|
where do venous thrombi typically originate? how do they grow?
|
sites of stasis
extend in the direction of blood flow |
|
|
what are lines of Zahn?
|
grossly and microscopically apparent laminations that represent pale platelet and fibrin deposits alternating with darker red cell-rich layers
indicate the thrombus has formed in flowing blood |
|
|
what are mural thrombi?
|
thrombi occurring in heart chambers or in the aortic lumen
|
|
|
what type of cells tend to be found in venous thromboses?
|
more enmeshed red cells
relatively few platelets |
|
|
what are the four possible fates of thrombi?
|
propagation
embolization dissolution organization and recanalization |
|
|
what is thrombus propagation?
|
accumulation of additional platelets and fibrin
|
|
|
what is thrombus embolization?
|
dislodging and travel to other sites in the vasculature
|
|
|
what is thrombus dissolution?
|
fibrinolysis, leading to the rapid shrinkage and total disappearance of recent thrombi
|
|
|
why is therapeutic administration of fibrinolytic agents (t-PA) in the setting of acute coronary thrombosis generally effective only when given in the first few hours?
|
extensive fibrin deposition and crosslinking in older thrombi renders them more resistant to lysis
|
|
|
what is thrombus organization and recanalization?
|
organization - ingrowth of endothelial cells, smooth muscle cells, and fibroblasts
recanalization - capillary channel formation that re-establishes the continuity of the original lumen, albeit to a variable degree |
|
|
what is worrisome about venous thrombi?
|
though they can cause congestion and edema in vascular beds distal to an obstruction, but they are far more worrisome for their capacity to embolize to the lungs and cause death
|
|
|
what is worrisome about arterial thrombi?
|
although they can embolize and cause downstream infarctions, a thrombotic occlusion at a critical site (e.g. a coronary artery) can have more serious consequences
|
|
|
where do most venous thrombi occur?
|
superficial or deep veins of the leg
|
|
|
in what vein do superficial venous thrombi typically occur?
|
saphenous veins
in the setting of varicosities |
|
|
what is the main worry in superficial venous thrombi?
|
they rarely embolize, so the main concern is that the local edema and impaired venous drainage predispose the overlying skin to infections and to varicose ulcers
|
|
|
where does deep venous thrombosis occur?
|
larger leg veins (at or above the knee)
|
|
|
why are deep venous thrombi more serious than superficial venous thrombi?
|
they are more prone to embolize to the lungs and give rise to pulmonary infarction
|
|
|
why are DVTs asymptomatic in approximately 50% of people?
|
the venous obstructions can be rapidly offset by collateral channels
in many people, DVTs are only recognized in retrospect after embolization |
|
|
why does bed rest and immobilization predispose patients to lower extremity DVTs?
|
reduces the milking action of the leg muscles, resulting in reduced venous return
|
|
|
what are the common predisposing factors for lower extremity DVTs?
|
bed rest and immobilization
congestive heart failure trauma surgery burns |
|
|
what is Trousseau syndrome?
|
aka migratory thrombophlebitis
In patients with malignancy-associated hypercoagulable states, the blood may spontaneously form clots in the portal vessels, the deep veins of the extremities (such as the leg), or the superficial veins anywhere on the body. These clots present as visibly swollen blood vessels (vasculitis), especially the veins, or as intermittent pain in the affected areas. The pathological phenomenon of clots forming, resolving and then appearing again elsewhere in the body has been named thrombophlebitis migrans or migratory thrombophlebitis. |
|
|
why is atherosclerosis a major cause of arterial thromboses?
|
it is associated with loss of endothelial integrity and with abnormal vascular flow
|
|
|
how can myocardial infarction predispose patients to cardiac mural thrombi?
|
causes dyskinetic myocardial contraction as well as damage to the adjacent endocardium
|
|
|
what are the particularly likely targets of cardiac and aortic mural thrombi? why?
|
brain
kidneys spleen rich blood supply |
|
|
what is DIC?
|
disseminated intravascular coagulation
sudden or insidious onset of widespread fibrin thrombi in the microcirculation not a primary disease, but rather a potential complication of any condition associated with widespread activation of thrombin |
|
|
what disorder is also known as consumption coagulopathy?
|
DIC (disseminated intravascular coagulopathy)
widespread microvascular thrombosis results in platelet and coagulation protein consumption |
|
|
what is an embolus?
|
detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin
|
|
|
unless otherwise specified, what should be considered the origin of emboli?
|
thrombi
|
|
|
from where do pulmonary emboli originate in more than 95% of cases?
|
leg deep vein thromboses
(not all DVTs progress to PEs, as DVTs occur 2-3 times more frequently than PEs) |
|
|
what is a saddle embolus?
|
thrombus that straddles a dividing blood vessel
often lethal because they prevent the entry of blood into the lung and cause acute anoxia typically originate in the veins of the lower extremities and are carried by venous blood to the vena cava and then through the right atrium and ventricle into the pulmonary artery |
|
|
what is a paradoxical embolism?
|
arterial thrombosis caused by embolism of a thrombus (blood clot) of venous origin through a lateral opening in the heart, such as a patent foramen ovale
|
|
|
at what amount of blockage are serious symptoms noted from pulmonary emboli?
|
60% or more of the pulmonary circulation
symptoms: sudden death, right heart failure, cardiovascular collapse |
|
|
what is cor pulmonale?
|
failure of the right side of the heart brought on by long-term high blood pressure in the pulmonary arteries and right ventricle of the heart
|
|
|
what is referred to by the term systemic thromboembolism?
|
emboli in the arterial circulation
|
|
|
what are the factors in where an arterial embolus lodges?
|
source of embolus
blood flow that downstream tissues receive |
|
|
what is a fat embolism?
|
microscopic globules of fat found in the circulation and impacted in the pulmonary vasculature after fractures of long bones (which have fatty marrow) or, rarely, in setting of soft tissue trauma and burns
|
|
|
what is fat embolism syndrome?
|
term applied to the minority of ppl that become symptomatic from fat emboli
characterized by pulmonary insufficiency, neurologic symptoms, anemia, and rapid-onset thrombocytopenia (with resultant diagnostic rash in 20%-50% of cases) |
|
|
in general, how much air is required in an air embolism to have a clinical effect in the pulmonary circulation?
|
more than 100cc
|
|
|
what is decompression sickness?
|
aka the bends
a particular form of gas embolism that occurs when individuals experience sudden decreases in atomspheric pressure |
|
|
how is decompression sickness caused?
|
when air is breathed at high pressure, increased amounts of gas (esp. nitrogen) are dissolved in blood and tissues
with rapid depressurization, the nitrogen comes out of solution in the tissues and blood rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints is responsible for the painful condition called the bends in the lungs, gas bubbles in the vasculature cause edema, hemorrhage, and focalatelectasis or emphysema called the chokes |
|
|
what is caisson disease?
|
a more chronic form of decompression sickness
|
|
|
how is acute decompression sickness treated?
|
place individual in high pressure chamber, which serves to force gas bubbles back into solution, followed by slow decompression
|
|
|
how is the onset of an amniotic fluid embolism characterized?
|
sudden severe dyspnea, cyanosis, and shock, followed by neurologic impairment ranging from headache to seizures and coma
if the patient survives the initial crisis, pulmonary edema typically develops, with DIC |
|
|
what is the cause of amniotic fluid embolism?
|
infusion of amniotic fluid or fetal tissue into the maternal circulation via a tear in the placental membranes or rupture of uterine veins
|
|
|
what is an infarct?
|
area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage
|
|
|
what are the causes of infarcts?
|
- thrombosis
- embolus - local vasospasm - hemorrhage into atheromatous plaque - extrinsic vessel compression |
|
|
in what type of organs are venous thrombosis more likely?
|
organs with a single efferent vein
|
|
|
how are infarcts classified?
|
color: red (hemorrhagic) or white (anemic)
infection: septic or bland |
|
|
where do red infarcts occur?
|
1) with venous occlusions
2) in loose tissues where blood can collect in the infarcted zone 3) in tissues with dual circulations that allow blood flow from an unobstructed parallel supply into a necrotic zone 4) in tissues previously congested by sluggish venous outflow 5) when flow is re-established to a site of previous arterial occlusion and necrosis |
|
|
where do white infarcts occur?
|
with arterial occlusions in solid organs with end-arterial circulation and where tissue density limits the seepage of blood from adjoining capillary beds into the necrotic area
|
|
|
what organs have end-arterial circulation?
|
heart
spleen kidney |
|
|
what is the dominant histologic characteristic of infarction?
|
ischemic coagulative necrosis
|
|
|
how long does it take for tissues to show necrosis?
|
4-12 hours
|
|
|
what are most infarcts ultimately replaced with?
|
scar
|
|
|
what type of necrosis is particular to CNS infarction?
|
liquefactive necrosis
|
|
|
when do septic infarctions occur?
|
when infected cardiac valve vegetations embolize or when microbes seed necrotic tissue
|
|
|
in cases of septic infarctions, into what is the infarct converted?
|
abscess
|
|
|
what is the most important determinant of whether vessel occlusion will cause damage?
|
availability of alternative blood supply
|
|
|
how does rate of occlusion development affect whether it causes infarction?
|
slowly deveoping occlusions provide time to develop alternate perfusion pathways
|
|
|
how quickly after being deprived of blood supply do neurons undergo irreversible damage?
|
3-4 minutes
|
|
|
how quickly after being deprived of blood supply do myocardial cells undergo irreversible damage?
|
20-30 minutes
|
|
|
how does oxygen content of blood affect whether an occlusion causes infarction?
|
a partial obstruction of a small vessel that would be without effect in an otherwise normal individual might cause infarction in an anemic or cyanotic patient
|
|
|
what is shock?
|
shock is characterized by systemic hypotension due either to reduced cardiac output or to reduced effective circulating blood volume
|
|
|
what are the consequences of shock?
|
impaired tissue perfusion
cellular hypoxia |
|
|
what are the three general categories for causes of shock?
|
cardiogenic shock
hypovolemic shock septic shock |
|
|
what is cardiogenic shock?
|
shock resulting from low CO due to myocardial pump failure
|
|
|
what is hypovolemic shock?
|
shock resulting from low CO due to loss of blood or plasma volume
|
|
|
what is septic shock?
|
shock that results from vasodilation and peripheral pooling of blood as part of a systemic immune reaction to bacterial or fungal infection
|
|
|
what is neurogenic shock?
|
shock resulting in hypotension, occasionally with bradycardia, that is attributed to the disruption of the autonomic pathways within the spinal cord
hypotension occurs due to decreased systemic vascular resistance resulting in pooling of blood within the extremities lacking sympathetic tone bradycardia results from unopposed vagal activity |
|
|
what is anaphylactic shock?
|
shock caused by systemic vasodilation and increased vascular permeability caused by an IgE-mediated hypersensitivity reaction
|
|
|
what type of bacteria currently causes septic shock most frequently?
|
gram positive > gram negative > fungi
|
|
|
what are the clinical examples of cardiogenic shock?
|
myocardial infarction
ventricular rupture arrhythmia cardiac tamponade pulmonary embolism |
|
|
what are the clinical examples of hypovolemic shock?
|
hemorrhage
vomiting diarrhea burns trauma |
|
|
what is the role of toll-like receptors in sepsis?
|
recognize microbial elements and trigger the responses that initiate sepsis
|
|
|
what are the metabolic abnormalities that accompany septic shock?
|
insulin resistance
hyperglycemia |
|
|
what is the standard of care for treatment of septic shock?
|
- appropriate antibiotics
- intensive insulin therapy for hyperglycemia - fluid resuscitation to maintain systemic pressures - physiologic doses of corticosteroids to correct relative adrenal insufficiency |
|
|
what syndrome is caused by superantigens? what is this similar to?
|
toxic shock syndrome
similar to septic shock |
|
|
what are the three stages of shock?
|
nonprogressive stage
progressive stage irreversible stage |
|
|
what is the nonprogressive phase of shock?
|
initial phase, during which reflex compensatory mechanisms are activated and perfusion of vital organs is maintained
|
|
|
what is the progressive phase of shock?
|
second phase, characterized by tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances, including acidosis
|
|
|
what is the irreversible phase of shock?
|
third and final phase, that sets in after the body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible
|
|
|
what neurohumoral mechanisms help to maintain CO and BP in the early nonprogressive phase of shock?
|
- baroreceptor reflexes
- catecholamine release - activation of the renin-angiotensin axis - ADH release - generalized sympathetic stimulation |
|
|
what is the net effect of the neurohumoral mechanisms in the early nonprogressive phase of shock?
|
tachycardia
peripheral vasoconstriction renal conservation of fluid |
|
|
what happens if the underlying causes of shock are not corrected in the early nonprogessive phase of shock?
|
passes imperceptibly to the progressive phase with widespread tissue hypoxia
|
|
|
what is the result of lactic acidosis in the nonprogressive phase of shock?
|
lowers the tissue pH and blunts the vasomotor response
arterioles dilate, and blood begins to pool in microcirculation |
|
|
how is widespread cell injury reflected in the irreversible phase of shock?
|
lysosomal enzyme leakage
|
|
|
how do patients present in hypovolemic and cardiogenic shock?
|
hypotension
weak, rapid pulse tachypnea cool, clammy, cyanotic skin |
|
|
how do patients present in septic shock?
|
hypotension
weak, rapid pulse tachypnea initially warm and flushed skin (b/c of peripheral vasodilation) |
|
|
what is the second phase of shock that those who survive the initial complications may enter?
|
period of renal insufficiency, marked by progressive fall in urine output and severe fluid and electrolyte imbalances
|
