Reduced plasma osmotic pressure is caused by what?
Albumin and liver disease decreases protein synthesis
Nephrotic syndrome leads to loss of proteins
How does sodium and water retention affect hydrostatic pressure and plasma osmotic pressure?
Result?
INC hydrostatic P
DEC osmotic P bc of dilution
Renal failure, can be caused by CHF
What can cause edema via lymphatic obstruction?
Trauma
Fibrosis
Tumor
Infection
How do you describe Transudative effusion?
Protein poor, serous, straw-colored
Characteristics of exudative effusion?
Protein rich, opaque, INC WBCs
Subcutaneous edema may signify what?
Cardiac or renal disease
What is a common characteristic of severe chronic renal disease?
CHF?
Liver disease?
Periorbital edema
Pulmonary edema
Ascites
Increased blood volume in tissue, either locally or systemically is called what?
Result of what?
Hyperemia
INC arterial blood delivery to a given location
Congestion is the result of what?
Causes what?
Chronic cases lead to what?
DEC blood outflow
INC hydrostatic pressure, leads to edema
Hypoxia and ischemia
Morphologically, what appearance do congested tissues take on?
Dusky, reddish-blue color (cyanosis) due to red cell stasis and deoxygenated hemoglobin
What is the 1st thing that happens in Hemostasis at the site of vascular injury?
What mediates this process?
Arteriolar constriction
Endothelin released from endothelium
Where do platelets come from?
Megakaryoctes from bone marrow
What do alpha-granules of platelets contain?
Fibrinogen
Factor V
vWF
What do delta-granules of platelets contain?
Calcium
ADP
Platelet adhesion occurs via what interaction?
What does this interaction cause?
GpIb - vWF
Activation
Activation of platelets induces what?
Shape change to increase surface area and increase negative charge at the surface
Degranulation
Release of TxA2
Platelets aggregate and link through what interaction?
Fibrinogen - GpIIb/IIIa
What induces conformational change to express the GpIIb-IIIa complex to be exposed?
ADP
What converts fibrinogen to fibrin?
What does this promote?
Thrombin
Further platelet activation, aggregation, contraction
What additional role does thrombin serve on endothelium?
Acts on normal endothelium to limit clot size
What is responsible for activating factors 9 and 10?
TF-7a
Thrombin feeds back and amplifies the coagulation cascade by activating what?
11, 8, 5
What does the PT measure?
What must you add?
Extrinsic pathway
TF, phospholipids, Ca
What does PTT measure?
What must you add?
Intrinsic
Negatively charged surface, phospholipids, Ca
What cleaves fibrin?
What is produced?
Plasmin
D-dimers
What does heparin activate?
What does this do?
antithrombin III
Inactivates thrombin, factors 9, 10, 11, 12
What does protein C do?
What does it require the help of?
Inactivates factors 5 and 8
Protein S
Defects of primary Hemostasis is associated with what?
Classic finding?
Mucosal cutaneous bleeding
Petechia (1-2mm) and purpura (4-10mm)
What can cause primary Hemostasis?
Renal failure leading to uremia and reduced platelet function
Thrombocytopenia
What is deficient in Glanzmann disease?
GpIIb-IIIa resulting in bleeding disorder bc platelets are impaired (primary Hemostasis)
What is Bernard-Soulier syndrome?
GpIb deficiency
What makes up Virchow triad?
Primary endothelial injury
Abnormal blood flow
Hypercoagulability
When does endothelial dysfunction result in a prothrombotic environment?
Chronic inflammation
HTN
Hyperlipidemia
Circulating toxins
In endothelial injury what are the Procoagulant effects?
What are the anti fibrinolytic effects?
DEC thrombomodulin
DEC protein C
DEC TF inhibitor
DEC t-PA
Turbulence normally occurs where?
Stasis?
Arteries and in the heart
Veins
What are clinical examples of altered blood flow?
Ulcerated atherosclerotic plaques
Aneurysms
Infarcted myocardial tissue
Prolonged immobilization (bed rest)
What is the defect in Factor 5 Leiden?
Most common among who?
Resistant to protein C
Caucasians 3-8%
What is the 2nd most common inherited cause of hypercoagulability?
What gene?
Prothrombin gene mutation (INC prothrombin)
20210A
Deficiency of what enzyme may result in a hypercoagulable state?
Results in what?
Cystathione B-sythase
Homocystein uri’s
What are some examples of acquired hypercoagulability?
Immobilization MI or AFib Trousseau's syndrome Oral contraceptives and Hyperestrogenic state Tissue injury Smoking HIT syndrome Antiphospholipid Ab syndrome
What is Trousseau’s syndrome?
Seen with malignant cancers (pancreatic, lung) where they reduce prothrombotic mucin
What is HIT?
Abs that complex unfractionated heparin and platelet factor 4 activates the platelets and end up becoming consumed making CLOTS
What is Antiphospholipid antibody syndrome?
What Ab levels may be elevated?
Recurrent vascular thrombosis, thrombocytopenia or recurrent fetal loss
Anticardiolipin Ab
What are the clinical presentations with Antiphospholipid antibody syndrome?
PE
Stroke
MI
Bowel infarction
What do lines of Zahn contain?
Indicates what?
Alternating red and tan regions regions (containing RBCs and platelets)
Thrombus formed in flowing blood
Where are the common sites of arterial thrombi?
Coronary, cerebral, femoral arteries
Where are the common sites of venous thrombi?
Veins of leg (superficial and deep)
Upper extremities
Thrombi occurring in the heart or within the aorta are called what?
Occur when?
Mural thrombi
MI or AAA
What happens in organization of thrombus?
Replaced by fibroblasts, smooth muscle and endothelial cells
What happens in recanalization of thrombi?
New capillaries and small vessels grow through the structure
What is the most common cause of increased hydrostatic pressure?
Impaired venous return
What are the most common symptoms with defects of secondary Hemostasis?
Due to what?
Bleeding into joints (hemarthrosis) or soft tissue
Coagulation factor deficiencies (hereditary or acquired)
What is characteristic of DIC?
Widespread microthrombi
Consumption of coagulation factors
Consumption of platelets
What are some causes that may lead to DIC?
Sepsis
Childbirth problems
Massive trauma
Malignancy
What do lab studies show in DIC?
Elevated PT and PTT
Low fibrinogen
INC D-diners
Thrombocytopenia
What type of cells may be found in DIC?
Intravascular hemolysis - Schistocytes
Vitamin K is essential for production of what?
Where is it found?
2, 7, 9, 10, Protein C, protein K
Leafy greens, synthesized by gut flora
What kind of patients exhibit Vitamin K deficiency?
Pts receiving warfarin/Coumadin
Malnourished or prolonged parenteral nutrition
Prolonged Antibiotics
Massive transfusion defined how?
What does it cause?
1.5 x blood volume in 24 hours
INC PT, PTT
DEC fibrinogen and platelets
What is coagulation factor inhibitor?
What factor inhibition is most common?
Acquired Antibody resulting in impaired factor function
Factor 8 (Hemophilia A)
A mixing study is used to determine what?
What will not correct if there is inhibitor present?
Whether abnormal clotting times are due to a decreased amount of factor (as in hemophilia) or due to presence of inhibitor
PTT
Pulmonary Embolisms originate where?
DVTs in the leg (95%)
What is a saddle embolus?
Straddles the pulmonary artery bifurcation
Sudden death or right heart failure from PE may occur when?
60% of PA circulation is obstructed
Where do systemic embolisms arise from?
80% from the heart (LV wall and LA dilation/fibrillation)
What are the other sites of systemic thromboembolism?
Aortic aneurysms
Atherosclerotic plaques
Cardiac valves (vegetational)
Paradoxical emboli
What is a paradoxical embolism?
Venous embolus that gains access to the systemic arterial circulation
Where do the majority of systemic thromboembolism sludge?
Lower extremities (75%) Brain (10%)
What causes fat and marrow embolism?
Where does it translocate?
Fractures of long bones
Venous sinuses and then travel to the lungs
What is fat embolism syndrome?
Characterized by what?
Symptomatic fat and marrow embolisms
Pulmonary insufficiency, neurological symptoms, anemia, thrombocytopenia
Air embolisms must be what size to produce a clinical effect?
How can they be introduced?
Greater than 100cc
Surgically (vascular, neurosurgical, laparoscopic)
What is decompression sickness? Aka what?
Person experiences sudden decreases in atmospheric pressure (ascending from deep sea dive)
Nitrogen precipitates out of solution into the blood and tissues
Aka bends or chokes
What is Caisson disease?
Persistence of gas emboli in the skeletal system leads to multiple foci of ischemic necrosis, most commonly in the femoral head, tibia, humerus
What causes amniotic fluid embolism?
Can cause what serious condition?
Infusion of amniotic fluid/fetal tissue into maternal circulation via a tear in placental membrane or rupture of uterine veins
DIC
What kind of cells are seen in an amniotic fluid embolism?
Squamous
What is infarction?
Due to what?
Ischemic necrosis via occlusion of arterial supply or venous drainage
Arterial thrombosis or arterial embolism
What is characteristic of a red infarct?
Tissue with a dual blood supply (LUNG)
Venous occlusion (torsion)
Previously congested tissue
Reperfused necrotic tissue after arterial occlusion
What is characterisitc of a white infarct?
What organs?
Arterial occlusions in solid organs with end-arterial circulation
Spleen, kidney, heart
When does a septic infarct occur?
What can it be converted to?
Infected cardiac valve vegetations embolize or when microbes seed necrotic tissue
Abscess w/greater inflammatory response
What causes shock?
Diminished CO or reduced effective circulating blood volume -> cellular hypoxia
What causes cardiogenic shock?
Low CO due to cardiac infarction, tamponade, arrhythmia
What causes Hypovolemic shock?
Low CO due to low blood volume (hemorrhage from burns)
What causes systemic inflammation?
Results in what?
Microbial infections, burns, trauma, pancreatitis
Hypoperfusion, cellular hypoxia
What is the most common cause of death in US ICUs?
Mortality rate?
Causative organism?
Septic shock
20%
Gram positive bacteria
What are the main characteristics of septic shock?
Vasodilation -> DEC BP
Increased permeability -> leakage and edema
Procoagulant state (INC thrombin), eventually DIC
What metabolic disturbances can septic shock cause?
Inflammatory cytokines impair what?
Insulin resistance and hyperglycemia
Adrenal insufficiency and defect of glucocorticoids
GLUT4
Cellular hypoxia and DEC ox-phos leads to what?
INC lactate production and lactic acidosis
How does septic shock affect organs?
Systemic hypotension, edema, vascular leakage, stasis, thrombi
What is the net effect/goal of reflex mechanisms during the Nonprogressive phase of shock?
Tachycardia, peripheral vasoconstriction, renal conservation of fluid
What are the reflex compensatory mechanisms during Nonprogressive phase of shock?
Baroreceptor reflex Catecholamines release ADH release Symp stimulation Activation of renin-angiotensin axis
What characterizes the progressive phase of shock?
Tissue hypoperfusion, lactic acidosis, further vasodilation and peripheral pooling and stasis
In cardiogenic/Hypovolemic shock, how does the patient present?
Septic shock?
Hypotension, tachypnea, weak, cool, clammy, cyanotic
Vasodilated, warm, flushed