Ch.3 Hemodynamic Disorder Pt.1 Flashcards
the accumulation of fluid in tissues resulting from a net movement of water into extravascular spaces
Edema
process of blood clotting that follows blood vessel damage.
Hemostasis
(excessive bleeding), which may compromise tissue perfusion and, if massive and rapid, lead to hypotension, shock, and death.
hemorrhage
Inappropriate clotting
thrombosis
migration of clots in the vasculature
Embolism
blood vessel obstruction and ischemic cell death
infarction
What underlies
- myocardial infarction
- pulmonary embolism
- cerebrovascular accident (stroke).
thromboembolism
Clotting and migration of clot
is an active process resulting from arteriolar dilation and increased blood inflow; it occurs at sites of inflammation and in exercising skeletal muscle.
Hyperemia
Red tissues, lots of O2 blood
Passive process resulting from impaired outflow of venous blood from a tissue
occurs systemically in *cardiac failure *and locally as a consequence of venous obstruction.
Congestion
Tissues are blue-red color (cyanosis) Acc. of deoxygenated hemoglobin
What kind of Congestion?
Microscopicall marked by** blood-engorged alveolar** capillaries and variable alveolar septal edema and intraalveolar hemorrhage.
acute pulmonary congestion
What kind of Congestion?
the septa become thickened and fibrotic and the alveolar spaces contain *numerous macrophages *laden with hemosiderin (“heart failure cells) derived from phagocytosed red cells.
chronic pulmonary congestion
the central vein and sinusoids are** distended with blood** and centrally located hepatocytes may undergo necrosis.
** Periportal hepatocytes, which experience less severe hypoxia because of their proximity to hepatic arterioles, may develop fatty change**
Acute hepatic congestion
What kind of Congestion?
the central regions of the hepatic lobules are congested, red-brown, and **slightly depressed **(owing to necrosis and cell loss)
are accentuated by surrounding zones of *tan, sometimes Fatty, periportal hepatocytes (nutmeg liver)
chronic passive liver congestion
Extravascular fluid can collecting in body cavities
effusion
Examples of?
1.pleural cavity (hydrothorax)
2.pericardial cavity (hydropericardium)
3.peritoneal cavity (hydroperitoneum, or ascites)
Effusion
Extravascular fluid can collecting in body cavities
severe, generalized edema marked by profound swelling of subcutaneous tissues and accumulation of fluid in body cavities.
Anasarca
In inflammation, edema is due to what?
Increased vascular permability
GOverns movment of fluid in and out of aterioles
Controled by Na+ and K levels
Hydrostaic Pressure
2
Under normal circumstances what is the **balance **of hydrostatic pressure and osmotic pressure?
outflow of fluid produced by hydrostatic pressure at the arteriolar end of the microcirculation is nearly balanced by inflow at the venular end owing to osmotic pressure.
GOverns movment of fluid in and out of venules
Controled by protein concentration
Osmotic Presure
What 2 trends in hydrostatic pressure and osmotic pressure cause :
increased movement of water into the interstitium and if the drainage capacity of the lymphatics is exceeded, edema results.
- Increased hydrostatic pressure
- diminished colloid osmotic pressure
Edema fluid that accumulates due to high Hydrostatic pressue or low osmotic pressure is:
protein-poor transudate
increased vascular permeability, inflammatory edema fluid is
Protein rich exudate
are mainly caused by disorders that impair venous return
Increases in hydrostatic pressure
Impaired venous return Causes What?
the lower extremity may cause edema restricted to the distal portion of the affected leg,
deep venous thrombosis
Increase in Hydrostatic Pressure
Impaired venous return Causes What?
leads to a systemic increase in venous pressure and, often, widespread edema.
Congestive Heart faliue
Increase in hydrostatic pressure
ALL DO WHAT?
- Congestive heart failure
- Constrictive pericarditis
- Liver cirrhosis
- Venous obstruction or compression
- Thrombosis
- External pressure (e.g.,mass)
- Lower extremity inactivity with prolonged dependency
All things that cause Stagnation in venous portion of vascular because arterial end is empty no pressure pushing= whole system to backup = high hydrostatic pressure= water pushed out.
Reduced cardiac output leads to pooling of blood in the _____ and** increased capillary hydrostatic pressure**
venous circulation
The Reduction in cardiac output also results inhypoperfusion of the kidneys, triggering the renin-angiotensin-aldosterone axis and inducing ______ (secondary hyperaldosteronism).
Sodium and water retention
secondary hyperaldosteronism
Reduced plasma albumin is a common feature of disorders in which edema is caused by ____
Decreases in colloid osmotic pressure
Protien. Accounts for almost half of the total plasma protein and is the biggest contributor to colloid osmotic pressure.
Albumin
All result in?
- Nephrotic syndrome
- Reduced albumin synthesis is seen in the setting of severe liver disease (e.g.,cirrhosis)
- protien malnutriotion
Decrease of Osmotic pressure (protien out)
Excessive retention of ____ (and associated water) can lead to edema by increasing hydrostatic pressure (owing to expansion of the intravascular volume) and **reducing plasma osmotic pressure **
Retention of Salt; Na+ and K
defined as the extravasation of blood from vessels, results from damage to blood vessels and may be exacerbated by defects in blood clotting.
Hemorrhage
- Trauma
- atherosclerosis
- inflammatory or neoplastic erosion of a vessel wall also may lead to::
Hemmorage
What kind of hemorrhage?
Hemorrhage may take the form of external bleeding or may accumulate within a tissue
no iron deficiency
Hematoma
Bruises or massive retroperitoneal hematoma rupure in aorta, hemothorax
What kind of hemorrhage?
minute (1 to 2mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces
Low platlet count, or defective platlet function
Petechiae
What kind of hemorrhage?
lightly larger (3 to 5mm) hemorrhages
Caused by trauma, vascular inflammation (vasculitis), and increased vascular fragility
Purpura
What kind of hemorrhage?
larger (1 to 2cm) subcutaneous hematomas (colloquially called “bruises”).
Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of** hemoglobin** (red-blue color) to** bilirubin** (blue-green color) and eventually hemosiderin (golden-brown
Ecchymoses
relatively trivial in the subcutaneous tissues may cause death if located in the ___
Brain bleed
chronic or recurrent external blood loss can lead to a what defiinceny?
Peptic ulcer or menstration
Anemia; iron deficiency
precisely orchestrated process **involving platelets, clotting factors, and endothelium **that occurs at the site of vascular injury and leads to the formation of a blood clot, which serves to prevent or limit the extent of bleeding.
Homeostatis
1st. markedly reduces blood flow to the injured area
* local seretion of endothelin vasoconstrictor
Transient effect, bleeding will resume
Arteriolar vasoconstriction
2nd Step
* Basment membrane exposed* (collagen)*
* Bind Von Willebrand factor (VWF); Promotes platelet adherence and activation
* Platlet undergo shape change (small round flat to **spickey) **
* Release secratory granules (ADP, TXA2 vasoconstrictor)
* Bring more plugs in
* Plug formed
Primary hemostasis: the formation of the platelet plug.
3rd step
* Injury exposes tissue factor
* Tissue factor binds & activates Factor VII (7)
* Cascade reaction activated
* Thrombi generated
* Thrombin cleaves circulating fibrogenn into insoluble Fibrin
* More paltlet agregation
* More plug
Secondary hemostasis: deposition of fibrin. Vascular injury exposes tissue factor
4th Step
* Polymerized fibrin is crosslinked covalently by factor XIII (13)
* Platlet agregate contracts
* Formation of solid permanent plug = no more beleediing
* Size of clot resticted by anticoagulatory mechaims
Clot stabalization
potent endothelium-derived vasoconstrictor.
endothelin
molecule that promotes platelet adherence and activation
produced by enothelial cells
von Willebrand factor (VWF)
What are 2 secretory granuales released by activated platlets?
ADP & TXA2 (vasoconstrictor)
a membrane-bound procoagulant glycoproteinthat is normally expressed by subendothelial cells in the vessel wall, such as smooth muscle cells and fibroblasts.
tissue factor
Tissue factor binds and activates factor ?
Factor VII (7)
Sets action of cascade that makes Thrombin
cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork, and is a potent activator of platelets, leading to additional platelet aggregation at the site of injury.
Thrombonin
Insoluble fibrin mesh does what? Green.
Prevent blood loss, forms plug to stop bleeding.
Acute phase protiens Il-1, Il-6 and TNF is released from kidney along with what?
Fibrogen proteins
participate in a series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot
Roman numerals; circulate as** inacitve enzymes** (zymgogens)
Coagulation Factors
when coagulation factors activate, many become protien cleaves enzymes that contains serine .
Serine proteases
- Sequential activation of clotting factor zymogens (normal is low level activation
- Amplication with endothelial damage
- Results in fibrin generation
*Sequential= mutlple steps for feedback inhibition.
Coagulation Casacade
Assesses the function of the proteins in the extrinsic pathway (factors X, VII, V, II [prothrombin], and fibrinogen).
prothrombin time (PT)
Lab test
assesses the function of the proteins in the intrinsic pathway (factors XII, XI, X, IX, VIII, V, II, and fibrinogen).
partial thromboplastin time (PTT)
Lab test
what pathway?
Deficiencies of factors V, VII, VIII, IX, and X are associated with ____ and prothrombin deficiency is incompatible with life.
moderate to severe bleeding
Deficiency in XI causes
only causes a mild bleeding disorder
Deficiency in XII causes
No bleeding disorder
What is most important control amongst coagulation factors, controls diverse aspct of hemostasis and linsks clotting to inflmation and repair
Thrombin
In coagulation Cascade
X to Xa is what?
most central point to both pathways. Activation makes fibrin.
Drugs= block both arms.
Needed to produce all coagulation factors, vitamin K deficency results is less coagulation
Vitamin K
Xa converts what to what?
Prothrombin(II) to Thrombin (IIa)
Thrombin IIa catalyzes what conversion?
Fibrogen to FIbrin
Xa inhibitors, Rivaroxaban, Apixanbam all do what?
Decrease Thrombin
Block Xa no conversion of prothombrin to thrombin
Direct thrombin ibhibitors, hirudin, aragtorban, dabiagatran (PO) all do what?
**All decrease Fibrin **
Block conversion of fibrogen to fibrin.
- Glycoprotien
- Expressed in sub-endothelial cells
- Major activator of coagulation system
- Basis for Prothrombin time PT = time for blood clot
- No contact with circulating bloood
Tissue Factor Thromboplastin (extrinsic)
Primary event is exposure of tissue factor in sub endothelial cells
Factor VII and VIIa
tissue factor activates X to Xa
Extrinsic coagulation cascase
Thrombin IIa makes what?
MORE THROMBIN
Factor VIII and Factor IX are deficient in people with ____, extrinsic tissue factor pathway shut off.
Hemophillia
- Produced by endothelial cells (not liver)
- Circulates bound to vWF
- Released only at site of damage
- Platlet agregation & adhesion to each other
Factor VIII
A VERY important for coagulationNEEDED as cofactor for activation of multiple component complexworking downstream to activate downdstream components
Calcium
How many complexes come together to changes X to Xa
2 complexes
- Phospholipid TF-Bearing
- Tissue Factor
- Substrate: Factor X
Extrinsic Xase
- Phosopholid: Platelet
- Enzyme: Factor IXa
- Co-factor Factor VIII (VIIa) substrate; Factor X
Intrinsic Xase
Reslts in clot formation, activataton if this enzyme activates platlets and they release calcium.
Factor IV (4)
EDTA in blood collection tube binds calcium which does what?
Prevents clotting
Crosslink fibrin make hemostatic plug*
* stabalizes fibrin plug
* absence= inadequate plug formation
* requires calcium as co-factor
* Activated by thrombin
Factor 13 (XIII)
- can actiavte factor XI -> XIa
- Importance in testing of coagulation system
- activated by contact of (-) charged substances (ex. silica)
-
Basis and inital factor in Parital Thromboplastin time PTT
*
Factor XII Hangeman Factor
Add plasma to what to start forming clot in intrinsic pathway? PTT
Negatively charged substance, ex.silica
Add plasma to what to start forming clot in extrinsic pathway? PT
Tissue factor
Edma may result in this, compromises resorption of fluid from interstitial spaces.
Ex. parasitic infection filariasis, elephantitis!
Lymphatic Obstruction
