Hemodynamics I Lecture (Dr. Galbraith) TEST 1 Flashcards
Edema and Effusions
- INCREASED Hydrostatic Pressure or DECREASED Colloid Osmotic pressure —-> Net movement of fluid out of Vessels
a) EDEMA is an accumulation of fluid in tissues
b) An EFFUSION is an accumulation of fluid within a Body Space or Cavity
- INCREASED Hydrostatic Pressure
a) Often due to Impaired Venous return, may be localized or Systemic - REDUCED Plasma Osmotic Pressure
a) ALBUMIN: Liver Disease —> DECREASED Synthesis; Nephrotic Syndrome —> LOSS of Albumin - Sodium and Water Retention
a) RENAL RAILURE - Lymphatic Obstruction
a) Traumatic Disruption, Tumors, Infection
Morphology and Clinical Features
1) Affected organs appear ENLARGED and HEAVY
a) Pulmonary Edema, Brain Edema
2) Subcutaneous Edema is visible on Physical Exam
3) EFFUSIONS:
a) May be Transudative (Protein POOR): Serous and straw-colored
b) Exudative (Protein RICH): Opaque, with Increased WBSc
c) May involved:
i) Peritoneal Space (AScited)
ii) Pleural Cavity
iii) Pericardial Space
4) Subcutaneous Edema may signify Cardiac or Renal Disease
a) Periorbital Edema characteristic of severe Chronic Renal Disease
5) Pulmonary Edema most commonly Secondary to Congestive Heart Failure
a) Rapid onset may be fatal
6) Ascites is often seen in context of Chronic severe liver disease
Hyperemia and Congestion
- INCREASED Blood Volume in tissue, either locally or Systemically
- HYPEREMIA: the result of Increased Arterial blood delivery to a given location
a) May often be Physiologic - CONGESTION: the result of Decreased Blood Outflow
a) Increased hydrostatic pressure, which may lead to Edema
b) In Chronic cases may lead to Hypoxia and Ischemia
Morphology of Congestion
- Grossly, congested tissue is “dusky” (CYANOTIC)
- Microscopically, Capillaries and Venues are ENGORGED, and often extravasated RBCs are seen in Interstitial Tissue
- Classic Examples:
a) Pulmonary Congestion
b) Hepatic Congestion (NUTMEG LIVER)
Hemostasis
- Arteriolar CONSTRICTION (Vasoconstriction)
- PRIMARY Hemostasis
a) Platelets form a PLUG - SECONDARY Hemostasis
a) Coagulation cascade forming an Insoluble Fibrin Meshwork - Clot STABILIZATION and Resorption
Platelets
GRANULES:
- Alpha Granules (Fibrinogen, FV, vWF)
- Gamma Granules (Ca2+, ADP)
SITES of DAMAGED ENDOTHELIUM:
- Exposed vWF and Collagen
- vWF Binds to Platelets surface Gp1B (Platelet Adhesion)
Platelet Activation
- Platelet Adhesion (BpIb- vWF) serves to ACTIVATE the Platelet:
A) SHAPE CHANGE:
i) Increased Surface Area
ii) Increased Negative Charge at Surface
B) DEGRANULATOIN
C) Production and RELEASE of THROMBOXANE A2
i) Positive Feedback mediator of Platelet activation and Aggregation
ii) Cycooxygenase required for Synthesis
Platelet Aggregation
- Platelets bind FIBRINOGEN to GpIIb/ IIIa
- Aggregated platelets, linked by Fibrinogen, form a Temporary Plug at the site of Endothelial Injury
Secondary Hemostasis
- A cascade of Enzymatic reactions with the goal of forming THROMBIN with PROTHROMBIN
a) thrombin coverts Fibrinogen to Fibrin
b) Promotes further Platelet activation, aggregation, and contraction
c) Acts on normal endothelium to limit clot size
Coagulation Cascade
- Initiated by injury to Endothelium, exposed TISSUE FACTOR, and Platelets
- TF-VIIa Complex activates IX and X, leading to a small amount of Thrombin
- Thrombin feeds back and amplifies the Cascade by activating XI, VIII, and V!!!!!!!!
Coagulation Cascade Cont
A) In VITRO, Divided into Three Pathways:
- PT and PTT measure FIBRIN Clotting time in Plasma by assessing function of the factors involved in these pathways
B) Prothrombin time (PT) measures the EXTRINSIC Pathway
- Add TF, Phospholipids, and Ca2+
C) Patrial Thromboplastin Time (PTT) measure the INTRINSIC Pathway
- Add Negatively charged surface, Phospholipids, and Ca2+
Factors limiting Coagulation
- Wash out of Factors
- Need for Negatively Charged Surface
- Normal Endothelium:
a) PROSTACYCLIN, NO —> INHIBIT Platelet Activation and Aggregation
b) Shields platelets from vWF, and shields coagulation factors from TF
c) THORMBIN induces release of t-PA by Endothelial cells, promoting FIBRINOLYSIS
d) Anticoagulant effects, including production of THROMBOMODULIN and PROTEIN C receptor
Fibrinolysis
- Fibrin cleaves by PLASMIN, producing Fibrin Split products
Endothelial Anticoagulant Effects
1) Heparin-like Molecule:
- Inactivates THROMBIN (also factors IXa and Xa)
2) Tissue Factor pathway Inhibitor:
- Inactivates Factor VIIa Complexes
3) Thrombomodulin:
- Activates Protein C (requires Protein S) and this complex inactivates factors Va and VIIIa!!!!!!!!!!!!
4) PGI2, NO and Adenosine Disphosphatase:
- Inhibit Platelet Aggregation
5) t-PA:
- Activates Fibrinolysis
Defects of Primary Hemostasis (Platelets)
- Associated with MUCOCUTANEOUS BLEEDING
a) Petechiae (1 - 2mm), Purpura (4 - 10mm) - *****May be ACQUIRED:
a) ASPIRIN inhibits Cyclooxyrgenase —> Decrease TxA2 —-> Decrease Platelet Aggregation
b) RENAL FAILURE —> Uremia —> Reduced Platelet Function
c) THROMBOCYTOPENIA
- *****May be HEREDIATARY:
a) GpIIb/ IIIa deficiency (GLanzmann)
b) GpIb deficiency (Bernard-Soulier)
c) vWF deficiency (von Willebrand disease)
