7 - Hemodynamics (2nd Half) Flashcards
Abnormal Blood Flow (Virchow): Turbulence contributes
To arterial and cardiac thrombosis by causing endothelial or dysfunction
Abnormal Blood Flow (Virchow): Turbulence and stasis contribute to thrombosis in several clinical settings (6)
Ulcerated atherosclerotic plaques
Aneurysms
Acute MI
Acute myocardial infarctions
Rheumatic mitral valve stenosis
Hyperviscosity
Sickle cell anemia
Hypercoagulability (Virchow)
AKA Thrombophilia
Is any alteration of the coagulation pathways that predisposes to thrombosis
Hypercoagulability (Virchow) is divided into
Primary (genetic)
Secondary (acquired) disorders
Hypercoagulability: Primary (Genetic) - Common (3)
*Mutation in Factor V (Leiden)
Mutation in prothrombin gene
Mutation in methyltetrahydrofolate gene
Hypercoagulability: Primary (Genetic) - Rare (3)
Anti-thrombin III Deficiency
Protein C Deficiency
Protein S Deficiency
Hypercoagulability: Primary (Genetic) - Very Rare
Fibrinolytic defects
Hypercoagulability: Secondary (Acquired) - High Risk for Thrombosis
- Prolonged bed rest or immobilization
- MI
- AFib (a SA node)
- Tissue damage (surgery, fracture, burns)
- Cancer (Pancreas)
- Prosthetic cardiac valves
- DIC
Hypercoagulability: Secondary (Acquired) - Low Risk for Thombosis
- Hyper estrogenic states (pregnancy)
- OCPs
Mnemonic to remember thrombophilia
THROMBI
T - Tissue Damage H - Hereditary (V leiden) R - Rest (prolonged) O - Obstetrics (eclampsia, abruptio) M - Malignancy B - Blood flow disturbances (MI, aneurysms, varicose veins) I - Immune mechanisms
Factor V (Leiden) Mutation is called the
G1691A mutation
Factor V (Leiden)/G1691A Mutation
Results in glutamine to arginine substitution at position 506 that renders factor V resistant to cleavage by Protein C
Important anti-thrombotic counter-regulatory pathway is lost
Recurrent DVT
Prothrombin gene mutation
Single nucleotide change (G20210A)
Elevated prothrombin levels
Threefold increased risk of venous thrombosis
Protein C
Anti-thrombotic factor made by liver
Vit. K Dependent
Binds to activated Facts 5 and 8
If patient has a clot in leg before age 50, suspect?
Genetic abnormality rather than environmental
Heparin-Induced thrombocytopenia (HIT) Syndrome
IOccurs following administration of unfractionated heparin
Antibodies to heparin +Platelet factor (pf)-4 complex and Pf-44 like proteins on the endothelial cells
Binding of antibodies results in activation, aggregation, and consumption (thrombocytopenia)
Low molecular weight heparin has less frequency
If you give unfractionated heparin, some part of heparin protein will also resemble proteins in the bod, so what ocurrs?
Cross reaction
Antiphospholipid Antibody Syndrome (APLA)
Previously called lupus anticoaglant syndrome
Name derived from binding of antibodies to epitopes on plasma proteins (e.g. prothrombin) that are induced or ‘unveiled’ by phospholipids
Antiphospholipid Antibody Syndrome (APLA):
The autoantibodies INDUCE a hypercoagulable state by? 3
Causing endothelial injury
Activating platelets and complement directly
Interactions with the catalytic domains of certain coagulation factors
Antibodies to beta-2 glycoprotein are expressed on?
Endothelial cells
Antibodies against anion phosphoplipids
Cardiolipin
What type of reaction is there for VDRL?
False positive
What happens in vitro? (I think it’s referring to VDRL)
Inhibits coagulation
What happens in vivo? (I think it’s referring to VDRL)
Hypercoagulable state
Clinical Features of APLA (10)
- Pulmonary embolism (following lower extremity venous thrombosis)
- Pulmonary hypertension (from recurrent subclinical pulmonary emboli)
- Stroke
- Bowel infarction
- Renovascular hypertension
- Renal microangiopathy
- Recurrent thrombosis
- Repeated miscarriages (due to ab-mediated inhibition of t-PA activity necessary for trophoblastic invasion of the uterus)
- Cardiac valve vegetations
- Thrombocytopenia
Morphology of Thrombus 3
- Develop anywhere in the cardiovascular system
2. Size and shape of thrombi depend on the site of origin and the cause
Sizes and shapes of thrombi depending on the site of origin and the cause
Venous thombi: at sites of stasis; extend IN DIRECTION of blood flow
Arterial thrombi: grow retrograde from the point of attachment
Lines of Zahn
Represent pale platelet and fibrin deposits alternating with darker red cell-rich layers
Are laminations seen in thrombi
*Signigy that a thrombus has formed in flowing blood
Distinguish ante mortem thrombosis from the bland non-laminated clots that occur postmortem
Thrombi occurring in heart are known as mural thrombi
Ante mortem Clot Characteristics (4)
- Adhere to vessel
- Have lines of Zahn
- Can’t be washed away
- Buffed in color
Postmortem Clot Characteristics (4)
- Do not adhere to vessel
- Absent Lines of Zahn
- Easily washed away
- Chicken fat appearance
Mural thombus
Occur in heart chambers or in the aortic lumen
- abnormal myocardial contraction
- Endomyocardial injury
- **Precursors of aortic thrombi
- ulcerated atherosclerotic plaque
- aneurysmal dilation
Cardiac Vegetations
- Thrombi on heart valves
- Infective endocarditis
- Nonbacterial thrombotic endocarditis
- *Libman-Sack’s endocarditis
Fate of Thrombus: 1st - Propagation
Thrombi accumulate additional platelets and fibrin
Fate of Thrombus: 2nd - Embolization
Thrombi dislodge and travel to other sites in the vasculature
Fate of Thrombus: 3rd - Dissolution
Result of fibrinolysis, which can lead to the rapid shrinkage and total disappearance of recent thrombi
Fate of Thrombus: 4th - Organization and recanalization
Older thrombi become organized by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts
Venous Thrombosis (Phlebothrombosis): Superficial Venous Thrombi
Saphenous veins affected in the setting of varicosities
Local congestion, pain, and if edema superadded, impaired blood supply –> ulcer
Venous Thrombosis (Phlebothrombosis): Deep Vein Thrombosis (DVT)
Larger leg veins: at or above the knee (e.g. popliteal, femoral, and iliac veins) - is more serious
More often embolize to the lungs and give rise to pulmonary infarction
C/F - local pain and edema
Causes of for Venous Thrombosis (5)
Migratory thrombophlebitis or Trousseau syndrome (seen in pancreatic carcinoma)
Bed rest and immobilization
CHF
Trauma, surgery, burns
Advanced age
Mnemonic to remember risk factors for DVT/Pulmonary embolism: 5H
Hypercoagulability (sickle cell, polycythemia)
Hypomobility (Prolonged bed rest)
Hereditary (Factor V)
Hormones (OCP)
Hyperhomocysteinemia
Causes of Arterial and Cardiac Thrombosis and Consequences (4)
Atherosclerosis
MI
Rheumatic heart disease
Consequences:
- local obstruction
- embolize peripherally - brain, kidneys, and spleen are particularly likely targets because of their rich blood supply
Disseminated Intravascular Coagulation (DIC): Defined
Sudden or insidious onset of widespread fibrin thrombi in the microcirculation
DIC: Causes (23)
Obstetrics complications
Advanced malignancy
DIC: Pathogenesis
Release of tissue factor and widespread endothelial injury
DIC: Complications
Platelet and coagulation protein consumption
Diffuse circulatory insufficiency, particularly in the brain, lungs, heart and kidneys
Embolism: Definied
Detached intravascular solid, liquid, or gaseous mass that’s carried by blood to a site distant from its point of origin
Pulmonary Embolism: Stats (4)
95% originate from leg (DVTS)
60-80% are clinically silent
Risk for more after having 1
Usually multiple
Course of an Embolus
- DVT
- Reaches the right side of the heart and into the pulmonary arterial tree (deoxygenated blood)
Can have 3 pathways
a. Main pulmonary arteries
b. Straddle the pulmonary arterial bifurcation (saddle embolism)
c. Pass out into smaller, branching arteries
In what conditions can an emboli go from right side to left and into systemic circulation (paradoxical embolism)?
ASD, VSD
Embolism: Clinical Features (5)
Sudden death
Right heart failure (cor pulmonale)
Cardiovascular collapse
Pulmonary infarction - embolus in the setting of left-sided cardiac failure (and compromised bronchial artery flow)
Pulmonary hypertension
Systemic Thromboembolism: Defined
Emboli in the arterial circulation
Systemic Thromboembolism: Source (3)
Intracardiac mural thrombi
Unknown origin
Can travel to a variety of sites
Systemic Thromboembolism: Major Sites (2)
Lower extremities (75%)
Brain (10%)
Systemic Thromboembolism: Causes
Infarction of the affected tissues due to atherosclerosis
Majority occur in the heart
Fat and Marrow Embolism (Rare)
Microscopic fat globules: with or without associated hematopoietic marrow elements in the circulation impacted in the pulmonary vasculature
Fat and Marrow Embolism (Rare): Causes (3)
Fracture of long bones (which have fatty marrow)
Soft tissue trauma (MVA)
Burns
Slide 70
Fat and Marrow Embolism (Rare): Pathogenesis (2)
Mechanical obstruction: Fat, micro emboli and associated red cell and platelet aggregates occlude the pulmonary and cerebral microvasculature
Biochemical injury: Release of free FAs from the fat globules exacerbates the situation by causing local toxic injury to endothelium and platelet activation and granulocyte recruitment
Fat and Marrow Embolism (Rare): Clinical Features (8)
- Pulmonary Insufficiency
- Neurologic Symptoms
- Anemia: red cell aggregation and/or hemolysis
- Thrombocytopenia - splenic sequestration
- Fatal in about 5 - 15%
- Sudden onset of tachypnea, dyspnea, and tachycardia
- Irritability and restlessness can progress to delirium or coma
- A diffuse petechial rash from thrombocytopenia
Air Embolism: General (5)
Gas bubbles within the circulation can coalesce to form frothy masses that obstruct vascular flow
Decompression sickness: seen when there is sudden decrease in atmospheric pressure
Scuba and deep sea divers
Underwater construction workers
Indivduals in unpressureized aircraft in rapid ascent
Air Embolism: Course (for skeletal muscles and joints)
If the diver ascends (depressurizes) too rapidly
The nitrogen comes out of solution in the tissues and the blood, causing
Rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints, leading to
Painful conditions called the bends
Air Embolism: Course (Lungs)
If the diver ascends (depressurizes) too rapidly
The nitrogen comes out of solution in the tissues and the blood in the LUNGS, forming
Gas bubbles in the vasculature, which can cause
Edema, hemorrhage, and focal atelectasis or emphysema, leading to
A form of respiratory distress called the chokes
Air Embolism: Caisson Disease (3)
Chronic form of decompression sickness
Persistence of gas emboli in the skeletal system leads to multiple foci of ischemic necrosis;
Common sites: femoral heads, tibia, and humeri
Amniotic Fluid Embolism (3)
Sudden sever dyspnea, cyanosis followed by shock
Neurological impairment
Pulmonary edema and septic shock
Amniotic Fluid Embolism: Course
Tear in placental membranes or rupture of uterine veins, causing
Infusion of amniotic fluid or fetal tissue into the maternal circulation –> causing amniotic fluid embolism
Amniotic Fluid Embolism: Histological Findings (4)
Squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, in the maternal pulmonary microvasculature
Marked pulmonary edema
Diffuse alveolar damage
Presence of fibrin thrombi in many vascular beds due to DIC
What is vernix caseosa?
White, cheesy surface coating to the skin of infants
Infarction: Defined
Area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage
Infarction: Causes (8)
- Thrombotic or embolic arterial occlusions
- Local vasospasm
- Hemorrhage into an atheromatous plaque
- Extrinsic vessel compression (e.g. by tumor)
- Torsion of a vessel (e.g. in testicular torsion or bowel volvulus)
- Traumatic Rupture
- Vascular compromise by edema (e.g. anterior compartment syndrome)
Morphology of an Infarct: According to Color
Red - hemorrhagic
White - anemic
Morphology of an Infarct: Based on Presence or Absence of Infection
Septic
Bland
Morphology of an Infarct: Wedge-Shaped
With the occluded vessel at the apex and the periphery of the organ forming the base
Red Infarcts occur (5)
- With venous occlusions (e.g. ovary)
- In loose tissues (e.g. lung) where blood can collect in the infarcted zone
- In tissues with dual circulations (e.g. lung and small intestine)
- In tissues previously congested by sluggish venous outflow
- When flow is re-established to a site of previous arterial occlusion and necrosis
Red Infarcts: Course
Extravasated red cells in hemorrhagic infarcts then
Phagocytosed by macrophages, then
Converts heme iron into hemosiderin, and then
Small amounts do not grossly impart any appreciable color, brown residuum
White Infarcts Occur With (3)
- Arterial occlusions in solid organs with end-arterial circulation (e.g. heart, spleen, and kidney)
- Where tissue density limits the seepage of blood from adjoining capillary beds into the necrotic area
- Infarcts resulting from arterial occlusions in organs without a dual blood supply typically become progressively paler and more sharply defined with time
Exception to white infarcts
Brain – liquefactive necrosis
Shock: Is a systemic hypoperfusion due to reduction in? 2
Cardiac Output
Effective circulating blood volume
Shock: Result
Hypotension
Impaired tissue perfusion and cellular hypoxia
Shock: Main Categories
- Cardiogenic
- Hypovolemic
- Septic
Shock: Others
- Neurogenic Shock
2. Anaphylactic Shock
Shock: Cardiogenic Shock (4)
Failure of myocardial pump
Intrinsic Myocardial Damage
- Infarction, Ventricular rupture, arrhythmia
Extrinsic compression
- Cardiac tamponade
Outflow obstruction
- Pulmonary embolism
Shock: Hypovolemic
Due to loss of blood of plasma volume
Hemorrhage
Fluid loss
- From severe burns, trauma, vomiting, diarrahea
Shock: Septic
Most common cause of death in ICU’s in USA
Dissemination of infection into vasculature
Causes: G(+), G(-) infection (endotoxic shock), fungal infections, superantigens
Endothelial cell activation and injury –> hypercoagulable state –> DIC
Shock: Septic - Components
Inflammatory Mediators: TNF, IL-1, IFN-γ, IL-12, and IL-18. high mobility group box 1 protein (HMGB1).
Reactive oxygen species and lipid mediators such as prostaglandins and platelet activating factor (PAF)
Endothelial cell activation and injury: (1) thrombosis; (2) increased vascular permeability; and (3) vasodilation –> DIC
Shock: Septic - *Metabolic Abnormalities
Insulin resistance and hyperglycemia. TNF and IL-1, stress-induced hormones
(Such as glucagon, growth hormone, and glucocorticoids), and catecholamine’s –> gluconeogenesis
- Frank adrenal necrosis due to DIC (*Waterhouse-Friderichsen syndrome)
Immune Suppression
Organ dysfunction
Shock: Septic - Symptoms (7)
- Systemic Vasodilation (Hypotension)
- Diminished cardiac contractility
- Endothelial injury and activation (Adult Resp. Distress Sydrome, ARDS)
- Activatation of coagulation system (DIC)
- Multi-organ system failure
- Liver, Kidney, CNS
- Death
Morphology of Shock: General and Brain
Failure of multiple organ systems
Brain: ischemic encephalopathy
Morphology of Shock: Heart (2)
Focal or widespread coagulation necrosis
Sub-endocardial hemorrhage
Morphology of Shock: Kidney
*Acute Tubular Necrosis
Extensive tubular ischemic injury
C/F - Oliguria, anuria, electrolyte disturbances
Morphology of Shock: Lungs
Pure Hypovolemic Shock
- Rarely affected as they are resistant to hypoxic injury
Shock caused by bacterial sepsis or trauma
- Diffuse alveolar damage (shock lung)
Morphology of Shock: GIT
Hemorrhagic enteropathy
Patchy mucosal hemorrhages and necroses
Morphology of Shock: Liver
Fatty Change
Central hemorrhagic necrosis with severe perfusion deficits
Stages of Shock: Non-Progressive (Early)
Compensatory Mechanisms: Increase HR and peripheral resistance and maintain perfusion of vital organs
Stages of Shock: Progressive
Tissue hypoperfusion
Renal insufficiency and electrolyte imbalance –> metabolic acidosis from lactic acidosis
Stages of Shock: Irreversible
Survival is not possible
Hypovolemic, Cardiogenic, Septic Shock Chart (Slide 103)
Check Slide 103
