Exam 2 O2 Transport, Blood Flow, Coagulation Flashcards
Blood flow
Volume movement along a pressure gradient w/in vascular bed
Blood Pressure
Blood moves from areas of high (arteries) to low pressure (veins)
Blood resistance
Opposing forces that deter blood flow (as resistance increased flow decreases)
Ohm’s Law of Circulatory Physiology
MAP = CO x TPR (Total Peripheral Resistance)
MAP = DBP + (Pulse pressure / 3)
Flow = _____ / _____
Flow = Pressure/Resistance ( F= P/R)
P = F x R
Pouisuille’s Law Flow =
Resistance = 8LN /πR^4
8 x Length x Viscosity / Pi x Radius to the fourth
Arterioles
Major site of resistance, profound effect on SVR
SVR =
(MAP-CVP) x 80 / CO
Vascular Resistance is regulated _____ by _____ and _____ by ____
Centrally, ANS, locally, tissues
Release of norepinephrine results in ______ via _____ receptors
Vasoconstriction, alpha1
Epinephrine results in ______ via ______ receptors in ______ arteries and _____ muscle vascular beds
Vasodilation, B2 adrenergic, coronary, skeletal
(Epi stimulates a1, a2, B1, B2, B3) The affinity of epinephrine for beta receptors is somewhat greater than its affinity for alpha receptors. When given in low doses, or by slow IV infusion in humans, the beta effects of epinephrine may predominate.
Local blood flow through tissues is regulated through _____ influenced by _____ sensing and release of _____ and _____
Autoregulation, endothelial, nitric oxide, prostacyclin
Steps of vascular smooth muscle contraction
Norepinephrine binds to the __ receptor
A __ protein, ___is activated
__ activates a _____ (“L” type) ____ channel, increasing intracellular ___
Simultaneously, ___ activates_____
____ splits a membrane ____, PIP2, forming two products:_____ and _____
____ releases _____ from intracellular stores in the________, further increasing intracellular ____
Increased intracellular _____ leads to VSM contraction via the ______
A1, G, Gq, voltage-gated, calcium, Ca, Gq, phospholipase C (PLC), PLC, lipid, diacylglycerol (DAG), inositol triphosphate (IP3), IP3, Ca, endoplasmic reticulum, Ca, Ca, myosin light-chain kinase mechanism
Circulating Hormones: Vasoconstriction (2)
Angiotensin II: Tubule glomerular feedback v Na and H2O deliver thereby decreasing MAP). Stimulates renin release.
Vasopressin (ADH): released from posterior pituitary in responses to increased osmolality, acts as vasoconstrictor at V1 receptors through Gq mechanism.
Circulating Hormones: Vasodilation (2)
Kinins (Bradykinin): Endothelial cell beta 2 kinin receptor activation causes cGMP and cAMP mediated vasodilation in adjacent VSM cells.
Natriuretic peptides (ANP/BNP): secreted after atrial/ventricular wall stretch, activated ANP/BNP on VSM receptors = vasodilation
Endothelium: Vasoconstrictors (1)
Endothelial: expressed after shear stress, hypoxia, circulating hormones (angiotensin 2, AVP) IP3 mediated vasoconstriction via endothelin receptors on VSM cells
Endothelium Vasodilators (2)
Prostacyclin (PGI2): Normal endothelium produces PGI2 from arachidonic acid
Nitric Oxide: cGMP mediated relaxation by free diffusion from endothelial to VSM cells. Endothelial NO is a major regulator of local and systemic blood flow!
Transcapillary Exchange of fluids, electrolytes and nutrients
Exchange of gases and nutrients is dependent on pressure gradient between capillary and interstitium.
Starling Law: Transcapillary fluid exchange
Determinants of fluid movement
Fluid movement = P x S (Pcap + πtissue) - (Ptissue + πcap)
Out. In
P = Permeability
S = Surface area
πcap = Plasma oncotic Pressure AKA colloid osmotic pressure (pull into capillary)
Pcap = capillary hydrostatic pressure (push out of capillary)
πtissue = Colloid osmotic (oncotic) pressure
Ptissue = Tissue hydrostatic Pressure
Pressure exerted by impermeable ______ PULL (πcap)
Albumin _____ %
Globulin _____
Fibrinogen ______
Others ______
plasma proteins
51, 17, 4, 28
Pressure exerted by blood on capillary wall function to _____ plasma water and electrolytes ____ of the capillary
(Pcap)
Push, out
Thrombi Development
Stationary blood clot formed w/in a vessel or a chamber of the heart (causes dramatic slowing of blood flow and more turbulent flow)
Emboli Development
Material that forms a clot w/in bloodstream. Traveling clot.
(Can be produced by fat, malignant neoplasm/tumor, collection of bacteria, air)
Vasospasm
Sudden constriction of arterial smooth muscles resulting in obstruction of flow. May be mediated by hormonal changes, food additives or environmental factors.
External compression
May be caused by trauma, tight cast, compartment syndrome
Structural alteration that can causes arterial/venous obstruction (4)
1) Valvular incompetence: superficial = varicose veins, deep = chronic venous insufficiency
2) Atherosclerosis
3) Aneurysms: localized arterial dilutions, bulge outward. (Saccular = one sided balloons out, Fuji form = both sides balloon out, berry = balloon has stem/neck)
4) AV fistula: AVM = most common and serious type, tangled = knot of arteries and veins found most commonly w/in brain
Steps of developing atherosclerotic plaque (4 steps)
1) Initiated by endothelial surface damage to ther arterial intima causing inflammatory response and increase in vessel wall permeability
2) LDL breach intimal layer, leukocytes and endothelial cells oxidize the lipids causing further damage
3) Simultaneously Plt’s aggregate at the site and release platelet-derived growth factor (PDGF); stimulates growth of smooth muscle cells
4) Media smooth muscle cells, normally confined to the other tunica, drawn to the intima and proliferate. (Plaques slowly enlarge, v Orifice of artery and v Perfusion)
Clinical consequences of acute and chronic arterial obstruction
Decreased distal flow and eventually ischemia.
Clinical consequence of superficial and deep vein obstructions
Venous stasis ulcers, pain, and edema
How do plt’s and factors of clotting cascade contribute to hemostasis
After injury endothelin is released and causes vasoconstriction
Platelets bind to exposed collagen via von Willebrand factor and become activated, activated platelets release granules containing mediators (ADP, serotonin, histamine, thromboxane), more platelets are recruited by the ADP that was released, platelet-thrombin coactivation = positive feedback at site of injury.
Fibrin clot: secondary hemostatic plug, intrinsic and extrinsic lead to the common final pathway called coagulation cascade
Clot reaction: antithrombotic counterregulation - fibrinolysis = clot dissolution, occurs as fibrin clot is forming. Factor XII, HMWK, Kallikrein and thrombin release plasminogen activators. These cleave plasminogen to form plasminogen. Plasminogen digests fibrinogen and fibrin and inactivates factor V and VIII
Indications of bleeding disorder
Assessment: pallor, jaundice, hemarthrosis, telangectasisa, petechiae, purport, ecchymosis, hematoma, occult or frank bleeding, hematochezia/melena, hematuria, hematemesis, epistaxis, geophysics, menorrhagia
CBC: to identify anemia, platelet count
PT/INR assess extrinsic pathway of coagulation
aPTT assess intrinsic pathway of coagulation
D-dimer reflects fibrinolysis
Family history of bleeding in both males and females
Von Willebrand disease
Family history of bleeding in males, newly acquired bruising
Hemophilia A or B
Drugs (especially aspirin and NSAIDS, anticoagulant therapy), thrombocytopenia
Excessive bleeding/bruising during/after surgery
Mild-severe deficiency of coagulation factors, Von Willebrand disease, thrombocytopenia, drug ingestion
Bleeding following initial hemostasis
Factor XIII deficiency
Vascular Purpura
Abnormality of vessels or supportive tissues
Ehlers-Danlo’s Syndrome
Deficient collagen and elastin
Vitamin C deficiency
Defective collagen synthesis
Aging
Loss of subcutaneous fat and changes in connective tissue
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)
Autosomal dominant, dilated torturous small blood vessels that easily bleed, vessel wall composed of single layer of endothelium
Common cause of thrombocytopenia (plt’s < 150,000)
4 causes
1) Decreased platelet production (float/B12 deficiency, radiation therapy, chemotherapy, drugs, aplastic anemia, cancer in bone marrow)
2) Decreased Platelet survival (Drugs like thiazides/digoxin/heparin/furosemide/abx, mechanical prosthetic heart valves, viral and bacterial infections, circulating immune complexes, increased destruction in the spleen, DIC
3) Splenic sequestration (pooling) (splenomegaly, hypothermia)
4) Platelet Dilution (Massive transfusions with blood stored for more than 24 hours)
Causes of Thrombocytosis (Platelets > 400,000)
3 causes
1) Transitory (due to stress/physical exercise)
2) Primary (polycythemia Vera or chronic granulocytic leukemia. Treatment with cytotoxic agents, antiplatelet or interferon therapy)
3) Secondary (Response to hemorrhage, disease process or splenectomy)
Causes of Qualitative Platelet Disorders (platelets dysfunctional concerning adhesion, aggregation or release reaction)
2 Causes
Inherited (Bernard-Soulier syndrome, Von Willebrand disease, thrombasthenia)
Acquired (more common) - Drug induced, renal failure, hematologist disease
Treat based on underlying disorder may require platelet transfusion
Common causes of inherited and acquired disorder of coagulation
1) Hemophilia
2) Von Willebrand Disease
3) Vitamin K deficiency
4) Disseminated Intravascular Coagulation
Hemophilia
Most common inherited coagulation disorder
Excessive bleeding. Hallmark = hemarthrosis (bleeding into joints)
Hemophilia A
Factor VIII deficiency
Treatment = cryoprecipitate or factor VIII concentrate
Hemophilia B (Christmas disease)
Factor IX deficiency
Treatment = FFP or cryoprecipitate
Von Willebrand Disease
Autosomal dominant
Disorder of factor VII carrier protein and platelet dysfunction. Excessive bleeding, prolonged bleeding time, prolonged aPTT. Normal platelet count and normal PT/INR.
Treatment: Desmopressin - releases Von Willebrand factor and factor VIII from vascular endothelial cells. Cryoprecipitate and human-P used to manage severe bleeding. Avoid aspirin use.
Vitamin K deficiency
In infancy
Deficiency of Vitamin K-dependent coagulation factors (II, VII, IX, X). Evidence of bleeding includes melena, umbilical bleeding, hematuria, intracranial hemorrhage, hypovolemic shock. Prophylactic administration of Vitamin K to newborns, fresh plasma or whole blood may also be needed.
Acquired deficiency. May occur w/ malnutrition, malabsorption, chronic hepatic disease, antibiotic therapy, oral anticoagulation therapy. Increased PT/INR but other coagulation studies are normal. Treat with parent earl administration of Vitamin K and address underlying condition.
Disseminated Intravascular Coagulation
Acquired hemorrhagic syndrome in which clotting and bleeding occur simultaneously
Causes: trauma, malignancy, burns, shock, abruptly placenta
Decreased fibrinogen and platelet counts
Increased bleeding time
^ PT/INR/aPTT, D-diner/fibrin split products
Treatment: correct underlying cause, support major organs, FFP, PRBC’s, or cryoprecipitate, heparin to minimize further consumption of clotting factors (controversial)
Flow is largely proportional to _____
____ and ____ have more flow than ____ and ____
Metabolism,
brain, heart, kidneys, gut
(tissues that are not metabolically active have low flow, tissues that are metabolically active have high flow like brain and heart, but organs like kidneys, gut, skeletal muscles have low flow)
The _____ determine regional flow to metabolically active tissue
Arterioles
Majority of blood stored in ____ until we become more active
Veins
_____ pick up excess water from____ and brings it back to ____
Lymph, interstitium, veins
Blood vessel linings:
adventitia, media, intima (teflon) vascular endothelial cells it’s anticlot (unless you injure it)
_____ heart pressure low, _____ heart pressure high, same amount of volume going through
Right, Left
Lymph capillary ____ with capillary bed, when you get to capillary beds __ comes out and ___ comes back in and you wash it away, ___ also leaks out and gets picked up by the _____ and comes back to _____ circulation (not getting rid of water = lymphodema)
Intertwines, O2, Co2, H2O, lymph, venous
F=___ , P= ____
P/R, FxR
RBC’s transport___ to tissues, remove___ from tissue
O2, CO2
CD3 cells found on ____ cells
T
RBC formation:
Pluripotential stem cells - Hematopoietic stem cells - committed progenitors of erythrocytes, granulocyts, monocytes, and megakaryocytes - immature hematopoietic precursors - mature functional blood cells
O2 combines with ___ portion to form_____, Each Hgb molecule can bind to __ molecules of O2,
hem, oxyhemoglobin, 4,
Partial pressure of O2 is the ______ affects tendency of O2 to bind with Hgb (expressed as PO2), PO2 high in _____ capillaries (O2 binds easily with Hgb), PO2 low in ____ capillaries (O2 released from Hgb), O2 saturation = amount of Hgb bound to oxygen,
pressure O2 exerts when dissolved in pulmonary, tissue
Labs for anemia:
CBC, Serum iron, serum ferritin
Labs for polycythemia:
H&H, CBC, Erythropoietin
Aplastic anemia -
stem cell disorder. V hematopoietic tissue, fatty marrow replacement, pancytopenia (low RBC, WBC, plt’s) Dx: bone marrow biopsy, Insidious onset of symptoms - weakness, fatigue, lethargy, pallor, dyspnea, palpitations, murmurs, tachycardia, thrombocytopenia (prone to bleeding) neutropenia (prone to infections), May need bone marrow transplant
Chronic renal failure anemia-
impairs erythropoietin, v RBC count with low H&H, give them erythropoietin
B12/folate deficiency anemia -
pernicious anemia r/t lack of Vit B12, deficient folate r/t alcohol, cirrhosis, pregnancy, infancy, Low RBC, WBC, Plt’s with ^ MCV; megaloplastic dysplasia, peripheral nerve degeneration, shillings test indicates low B12, achlordydria (absence of acid in GI secretions), altered personality/dementia/spastic weakness (r/t B12 deficiency) Give B12, folate or both
Iron deficiency anemia:
most common nutritional deficiency in the world. Microcytic RBC’s, low MCV, MCH and MCHC. V Serum ferritin, v serum iron, ^ Total Iron Binding Capacity, Pica (craving no food substances), Koilonychias (spoon shaped nails), Blue sclera, Give ferrous sulfate or ferric glucosamine,
Thalassemia -
RBC destruction (hemolysis), Hypochromic, microcytic RBC’s, MCV, MCH and MCHC are low, erytrhoblastic hyperplasia, Blood transfusions, splenectomy, chelation, bone marrow transplant, genetic counseling,
Sickle cell anemia -
RBC’s of different shapes and sizes, recurrent pain, Tx: Stem cell transplant
Hereditary Spherocytosis -
defective RBC membrane skeleton, altered membrane properties, altered cell metabolism, autosomal dominant, RBC’s fragile microspherocytes w/ ^ destruction of sphrocytes, ^ Hgb concentration, Tx = splenectomy
Glucose-6-phosphate Dehydrogenase deficiency:
RBC membrane destruction, Tx: preventative w/ drugs that trigger hemolytic episodes, aggressive infection management
Hemolytic disease of of newborn -
maternal antibodies against antigen on fetal RBC, Tx: RhoGAM to mother before or after delivery, severe cases = in utero blood transfusion an dearly delivery
Acute blood loss anemia -
tachycardia, orthostatic hypotension, shock and death occur with 50% loss of circulating volume, Tx: Blood volume replacement (crystal loads, colloids, fresh whole blood)
Polycythemia Vera -
transformation of bone marrow stem cells, ^ RBC mass, leukocytosis, thrombocytosis, ^ uric acid r/t excess proliferation, normal O2 sat, ^ viscosity. Tx: reduce blood volume, viscosity, RBC mass and platelet count w/ phlebotomy, radioactive phosphorus, chemotherapeutic agents. No cure.
Secondary Polycythemia -
r/t chronic hypoxemia w/ ^ erythropoietin production. ^RBC production w/o increase in WBC’s or platelets. Identify and manage underlying cause of hypoxemia.
Relative Polycythemia -
r/t dehydration with spurious increase in RBC production. ^H&H and RBC count, Tx: Recognize and mange underlying cause, fluids.
RBC O2 saturation and content.
Saturation = amount of O2 on HGb,
O2 content = How much O2 gets on Hgb and how much gets off to the tissues.
AVO2 (arterial venous oxygen)
difference is how much O2 tissues are taking out and using in mitochondria,
Lymph capillary anatomy:
intertwines with capillary bed, when you get to capillary beds O2 comes out and CO2 comes back in and you wash it away, H2O also leaks out and gets picked up by the lymph and comes back to venous circulation (not getting rid of water = lymphodema)
Artery anatomy:
Intima (endothelial cells in direct contact with blood as it flow through the vessel “teflon”, Media (smooth muscle tissue thickest section of artery), Adventitia (collagenous connective tissue)
Vein anatomy:
Intima (endothelial cells in direct contact with blood as it flow through the vessel “teflon”, Media (smooth muscle tissue thickest section of artery), Adventitia (collagenous connective tissue. Thickest section in veins) “poorly developed medial layer permites greater capacitance.
Capillary anatomy:
single thick endothelial cells attached to basement membrane, pores between endothelial cells determine permeability of capillary, “capillaries permit ready diffusion of O2 and nutrients because it’s comprised only of endothelial cell.
