Exam IV: Hemodynamic Disorders and Thromboembolic Diseases I

Question 1

Body Water

Answer 1

60% of lean body weight is water
Two thirds of the body’s water is intracellular
Remainder is in extracellular compartments
About 5% of total body water is in blood plasma

Question 2

Edema

Answer 2

Movement of water and low molecular weight solutes (salts) between the intravascular and interstitial spaces

Controlled primarily by opposing effect of:
Vascular hydrostatic pressure
Plasma colloid osmotic pressure

Increased interstitial fluid: increased capillary pressure and diminished colloid osmotic pressure
Fluid accumulation: movement of water into tissues (or body cavities) exceeds drainage
Abnormal increase in interstitial fluid within tissues= edema

Question 3

Fluid Collection in Cavities

Answer 3

Fluid collections in the different body cavities
Hydrothorax
Hydropericardium
Hydroperitoneum (ascites)

Question 4

Ansarca

Answer 4

Severe and generalized edema with widespread subcutaneous tissue swelling
When the patient is in multi organ system failure, all the systems are starting to shut down and the patient is completely swollen; can sometimes recover from this; very puffy all over like in hands, cheeks, feet. abdomen

Question 5

Transudate

Answer 5

Edema caused by:
Increased hydrostatic pressure
Reduced plasma protein

Typically a protein-poor fluid
Heart failure, renal failure, hepatic failure, and certain forms of malnutrition

Question 6

Mechanisms of Edema

Answer 6

Heart Failure:
increased capillary hydrostatic pressure leading to edema
decreased renal blood flow leading to the activation of the renin-angiotensin system + renal failure = retention in Na+ and H2O, which increases blood volume causing edema

Malnutrition, decreased hepatic synthesis, nephrotic syndrome: decreased plasma albumin and plasma osmotic pressure leading to edema

Question 7

Inflammatory Edema

Answer 7

Protein-rich exudate

Result of increased vascular permeability- increased endothelial gaps

Question 8

Lymphedema

Answer 8

Impaired lymphatic drainage
Typically localized
Causes: chronic inflammation with fibrosis, invasive malignant tumors, physical disruption, radiation damage

When you have edema, the lymphatics will try to move that fluid from interstitial tissue and move to vascular space
If lymphatics cannot take the fluid and move it = lymphatic edema
Tumors will clog the lymphatic drainage so fluid cannot get where it needs to go
Physical disruption: removing lymph nodes
Radiation: either tumor or something else, the area around it will have fibrosis and chronic inflammation

Question 9

Lymphokinetics

Answer 9

Highest to lowest pressure
Blood capillaries, interstitial fluid, lymph capillaries, lymph veins, lymph ducts, and large circulation veins (system circulation)

Question 10

Lymphatic Obstruction

Answer 10

Certain infectious agents, parasitic filariasis

Lymphatic obstruction:
Extensive inguinal lymphatic and lymph node fibrosis
Edema of the external genitalia and lower limbs
Massive = elephantiasis, which is permanent

Microfilarae – parasite in 3rd world country where animal/humans defecate on ground and humans walk on it and parasites get in and get into lymph nodes causing chronic inflammation and fibrosis from the parasitic eggs
Edema of the lower limbs and genitalia = elephantiasis

Question 11

Surgical Lymphatic Obstruction

Answer 11

Complicate surgical removal and/or irradiation
Breast cancer and associated axillary lymph nodes

Radical mastectomies- used to remove the breast and axillary cavity lymph nodes… problem is when you remove/radiate those nodes, that arm will become enlarged with edema
Better with conservative therapy where they inject radioactive dye and the cancerous lymph nodes will light up and remove just those instead of removing all of them

Question 12

Lymphatic Obstruction: Morphology of Edema

Answer 12

Morphology
Edema is easily recognized grossly; ECM looks white
Microscopic examination: clearing and separation of the extracellular matrix and subtle cell swelling

Most commonly seen:
Subcutaneous tissues, lungs, and brain

Question 13

Lymphatic Obstruction: Subcutaneous Edema

Answer 13

Diffuse or more conspicuous in regions with high hydrostatic pressures
Distribution is influenced by gravity: legs when standing, the sacrum when recumbent

See with congestive heart failure – look at legs and notice fluid is much more distributed = collection of fluid in lower extremities
Standing and walking – see in legs and ankles
Laying flat: legs don’t look swollen… but has congestive heart failure… sacrum will have those edematous changes not the legs

Question 14

Lymphatic Obstruction: Pitting Edema

Answer 14

Finger pressure over substantially edematous subcutaneous tissue
Displaces the interstitial fluid and leaves a depression

When on feet all day, pregnancy, etc.

Question 15

Lymphatic Obstruction: Renal Dysfunction

Answer 15

Edema secondary to renal dysfunction
Affect all parts of the body
Manifests in tissues with loose connective tissue matrix (eyelids)
Periorbital edema: characteristic finding in severe renal disease

Renal dysfunction: if patient has edema around eyes and not see edema anywhere else (periorbital) = indicates renal disease/failure

Question 16

Lymphatic Obstruction: Soft Tissue Edema

Answer 16

Important because it signals underlying cardiac or renal disease
Impairs wound healing or the clearance of infection

Most patients with edema are older and have chronic illness, or diabetic (sometimes with wound) = must get rid of edema/extra fluid
Cannot inject needle into edematous tissue because like sponge and can’t do that to a sponge

Question 17

Lymphatic Obstruction: Pulmonary Edema

Answer 17

Lungs are often two to three times their normal weight
Sectioning yields frothy, blood-tinged fluid from mixture of air, edema, and extravasated red cells
Common clinical problem
Most frequently seen with left ventricular failure

In a patient that is intubated, and starting to see pink frothy stuff coming out of tube, need to check their heart = pulmonary edema
Red cells outside of the vasculature have been mixing with fluid

Question 18

Lymphatic Obstruction: Brain Edema

Answer 18

Localized or generalized depending on the nature and extent of the pathologic process or injury

Generalized edema:
Brain is grossly swollen with narrowed sulci
Distended gyri show evidence of compression against the unyielding skull

Not much room so edema doesn’t have anywhere to go because thick skull, so the brain stem can herniate through foramen magnum or brain stem vascular supply can be compressed
Either condition can injure the medullary centers= severe injury or death

Question 19

Hyperemia

Answer 19

Stem from locally increased blood volumes

Hyperemia: active process and arteriolar dilation
Sites of inflammation and skeletal muscle during exercise
Leads to increased blood flow
Affected tissues turn red (erythema)
Engorgement of vessels with oxygenated blood

Question 20

Congestion

Answer 20

Passive process
Reduced outflow of blood from a tissue
Systemic like cardiac failure

Local: isolated venous obstruction
Dusky reddish-blue color (cyanosis): red cell stasis and accumulation of deoxygenated hemoglobin

Question 21

Chronic Passive Congestion

Answer 21

Lack of blood flow causes chronic hypoxia and results in ischemic tissue injury and scarring

Capillary rupture: cause small hemorrhagic foci
Subsequent catabolism of extravasated red cells
Leave residual telltale clusters of hemosiderin-laden macrophages

Question 22

Morphology of Congestion: Acute vs. Chronic

Answer 22

Cut surfaces: discolored due to the presence of high levels of poorly oxygenated blood

Acute pulmonary congestion:
Engorged alveolar capillaries
Alveolar septal edema
Focal intra-alveolar hemorrhage

Chronic pulmonary congestion:
Septa are thickened and fibrotic
Alveoli often contain numerous hemosiderin-laden macrophages
Heart failure cells

Question 23

Acute vs. Chronic Hepatic Congestion

Answer 23

Acute hepatic congestion:
Central vein and sinusoids are distended
Centrilobular hepatocytes can be frankly ischemic

Chronic passive hepatic congestion:
Centrilobular regions are grossly red-brown
Areas are accentuated against uncongested parenchyma
Nutmeg liver
Centrilobular hemorrhage
Hemosiderin-laden macrophages
Degeneration of hepatocytes

Question 24

Hemorrhage

Answer 24

Extravasation of blood into the extravascular space
Increased tendency to hemorrhage (usually with insignificant injury)
Occurs in a variety of clinical disorders
Collectively called hemorrhagic diatheses
Vascular fragility from medication (blood thinners) = can causes bruising from hemorrhaging

Question 25

Patterns of Tissue Hemorrhage

Answer 25

Distinct patterns of tissue hemorrhage
Hemorrhage may be external
Contained within a tissue
Hematoma- in soft tissue

Question 26

Petechiae

Answer 26

Minute 1- to 2-mm (very tiny pinpoint) hemorrhages into skin/cutaneous, mucous membranes, or serosal surfaces

Most commonly associated:
Locally increased intravascular pressure
Low platelet counts (thrombocytopenia)
Defective platelet function (as in uremia)

Platelet count drop = thrombocytopenia, start to see pinpoint hemorrhages in serosal parts of organs

Question 27

Purpura

Answer 27

Slightly larger (≥3 mm) hemorrhages compared to petechiae
Associated with many of the same disorders that cause petechiae 
Secondary to trauma, vascular inflammation (vasculitis), or increased vascular fragility (amyloidosis)

Question 28

Ecchymoses

Answer 28

Larger (>1 to 2 cm) subcutaneous hematomas (bruises)
Red cells in these lesions are degraded and phagocytized by macrophages

Hemoglobin (red-blue color) is enzymatically converted into bilirubin (blue-green color)
Hemosiderin (gold-brown color), accounting for the characteristic color changes in a bruise

Question 29

Hemorrhage in Body Cavities

Answer 29

Large accumulation of blood in a body cavity
Hemothorax
Hemopericardium
Hemoperitoneum
Hemarthrosis (in joints)

Question 30

Normal Hemostasis

Answer 30

Consequence of tightly regulated processes
Maintain blood in a fluid state in normal vessels
Permit the rapid formation of a hemostatic clot at the site of a vascular injury
Normally occurring process in body because regulates blood in vessels

Question 31

Thrombosis

Answer 31

Pathologic counterpart of hemostasis that involves blood clot (thrombus) formation

Favored by: Exposure basement membrane and collagen = activates, and platelets release granules causes more activation

Both hemostasis and thrombosis involve three components:

1. Vascular wall (particularly the endothelium)
2. Platelets
3. Coagulation cascade

Question 32

Steps of Clot Formation

Answer 32

1. Vasoconstriction: short time then vasodilation occurs
2. Exposed collagen and basement membrane = platelets activated and become adherent/sticky
3. Platelets adhere to basement membrane and change conformational shape and squishes down and granular release (ADP and TxA2) to call other platelets to area (recruitment)
4. End up with primary hemostatic plug temporarily
5. Other things adhere like RBCs and WBCs forming the secondary hemostatic plug, then hardens
6. Endothelial cells release factors that lyse the clot and break it up via blocking coagulation cascade

Question 33

Endothelial Cells

Answer 33

Key players in the regulation of homeostasis
Exhibit antiplatelet, anticoagulant, and fibrinolytic properties

After injury or activation acquire numerous procoagulant activities; injury from endotoxins, bacteria, high BP, etc.
Activated by infectious agents, hemodynamic forces, plasma mediators, and cytokines

Intact, nonactivated endothelial cells inhibit platelet adhesion and blood clotting
Endothelial injury or activation results in a procoagulant phenotype that enhances thrombus formation

Question 34

Anti-Platelet Effects

Answer 34

Intact endothelium prevents platelets from engaging the highly thrombogenic subendothelial ECM

Nonactivated platelets: do not adhere to endothelial cells
Even if platelets are activated, prostacyclin (PGI2) and nitric oxide produced by the endothelial cells impede platelet adhesion

Endothelial cells also elaborate adenosine diphosphatase to degrade adenosine diphosphate (ADP)
Further inhibits platelet aggregation

Question 35

Anticoagulant Effects

Answer 35

Mediated by endothelial membrane-associated heparin-like molecules

Thrombomodulin: binds to thrombin and converts it from a procoagulant into an anticoagulant via its ability to activate protein C, which inhibits clotting by inactivating factors Va and VIIIa (5a and 8a)

Tissue factor pathway inhibitor is a cell surface protein that directly inhibits tissue factor-factor VIIa and factor Xa activities aka anticoagulant

**These are all endogenous to our system

Question 36

Anticoagulant Effects: Heparin-like Molecules

Answer 36

Heparin-like molecules: act indirectly and consist of cofactors that enhance the inactivation of thrombin and several other coagulation factors
Through the use of plasma protein antithrombin III

Question 37

Fibrinolytic Effects

Answer 37

Endothelial cells synthesize tissue-type plasminogen activator (t-PA)
Protease that cleaves plasminogen to form plasmin
Plasmin cleaves fibrin to degrade thrombi

Endothelial cells caused the clot to develop, but now must break up the clot once job is completed

Question 38

Platelet Effects

Answer 38

Endothelial injury allows platelets to contact the underlying extracellular matrix

Subsequent adhesion occurs through interactions with von Willebrand factor (vWF), a product of normal endothelial cells and an essential cofactor for platelet binding to matrix elements

Cytokines present because bacterial endotoxins could be present during injury

Question 39

Procoagulant Effects

Answer 39

Response to cytokines (TNF or IL-1) or bacterial endotoxin

Endothelial cells synthesize tissue factor, a major activator of the extrinsic clotting cascade
Activated endothelial cells augment the catalytic function of activated coagulation factors IXa and Xa

Question 40

Antifibrinolytic Effects

Answer 40

Endothelial cells secrete inhibitors of plasminogen activator (PAIs)
Limit fibrinolysis and tend to favor thrombosis

Question 41

von Willebrand Disease

Answer 41

Collagen of basement membrane= exposure to vWF
No “houses” aka vWF, the platelet roof will not be able to bind so bleeding is prolonged… either missing vWF or deficiency = von Willebrand disease

No vWF – no clotting = prolonged bleeding

Question 42

Bernard Soulier Syndrome

Answer 42

If missing roofs aka glycoprotein 1B (Gp1B), won’t get platelet to adhere to vWF so still issue for clotting = Bernard Soulier syndrome

Question 43

Glanzmann Thrombasthenia

Answer 43

Have platelets, but no C shaped things aka Gp2b-3a = no connection of platelets = Glanzmann thrombasthenia

Question 44

Platelets

Answer 44

Disc-shaped, anucleate cell fragments
Shed from megakaryocytes in the bone marrow into the blood stream

Play a critical role in normal hemostasis
Forming the hemostatic plug that initially seals vascular defects
Providing a surface that recruits and concentrates activated coagulation factors

Question 45

Platelet Functions

Answer 45

Function depends on several glycoprotein receptors
Contractile cytoskeleton
Two types of cytoplasmic granules
1. α-Granules
2, Dense (or δ) granules 

Following vascular injury platelets encounter ECM constituents- collagen and the adhesive glycoprotein vWF
On contact with these proteins, platelets undergo:
Adhesion and shape change, secretion (release reaction), and aggregation

Question 46

Platelet Adhesion to ECM

Answer 46

Mediated largely via interactions with vWF
Acts as a bridge between platelet surface receptors (glycoprotein Ib) and exposed collagen
vWF-GpIb associations: necessary to overcome the high shear forces of flowing blood

Genetic deficiencies of vWF or its receptor result in bleeding disorders
Von Willebrand Disease- no vWF
Bernard-Soulier syndrome – no glycoprotein 1B (receptor)

Question 47

Platelet Secretion

Answer 47

Occurs soon after adhesion
Various agonists can bind platelet surface receptors
Initiate an intracellular protein phosphorylation cascade
Leads to degranulation (dependent on conformational change of platelets)

Release of the contents of dense-bodies:
Important
Calcium is required in the coagulation cascade
ADP is a potent activator of platelet aggregation that causes additional ADP release and amplifies aggregation process

Question 48

Platelet Activation

Answer 48

Appearance of negatively charged phospholipids (particularly phosphatidylserine) on their surfaces
Bind calcium and serve as critical nucleation sites for the assembly of complexes containing the various coagulation factors

Question 49

Platelet Aggregation

Answer 49

Platelet aggregation follows adhesion and granule release

Vasoconstrictor thromboxane A2: TxA2
Important platelet-derived stimulus
Amplifies platelet aggregation
Formation of the primary hemostatic plug

Initial wave of aggregation is reversible

Question 50

Platelet Aggregation: Activation of Coagulation Cascade

Answer 50

Concurrent activation of the coagulation cascade:
Generates thrombin
Stabilizes the platelet plug via two mechanisms:
1. Thrombin binds to a protease-activated receptor on the platelet membrane in concert with ADP and TxA2 causes further platelet aggregationand platelet contraction (dependent on the platelet cytoskeleton)
Creates an irreversibly fused mass of platelets
Constitutes the definitive secondary hemostatic plug
2. Thrombin converts fibrinogen to fibrin in the vicinity of the platelet plug to cement the platelets in place

Question 51

Platelet Aggregation: Fibrinogen

Answer 51

Noncleaved fibrinogen is an important component of platelet aggregation

Platelet activation by ADP:
Triggers a conformational change in the platelet GpIIb-IIIa receptors
Induces binding to fibrinogen
Large protein that forms bridging interactions between platelets that promote platelet aggregation