Lecture 4: Hemodynamics and Shock I (Dr. Singh) Flashcards
What is edema?
Fluid collection in the interstitial space
What is an effusion?
Can you state an example of a space where an effusion would exhist in?
Fluid collection in a potential space (body cavity)
- Pleural space
- Peritoneal space (ascites)
- Pericardial space
- Joint space
What are the two ways you can get an increased intravascular hydrostatic pressure?
- Sodium and water retention
- Congestion
What is hyperemia?
Too much blood is arriving
(physiologic, occurs after a workout for example)
What is congestion?
Not enough blood is leaving
(pathologic)
What controls hyperemia?
Precapillary sphincter
Soft tissue edema/pitting edema is usually indicative of what?
Heart failure
Describe the mechanism of heart failure leading to edema/effusion
During heart failure, the heart fails to perfuse the body.
THEN
When the kidneys are underperfused, the kidneys will activate the RAAS system in order to retain water
This leads to the overall increase in dilute water retention –> edema/effusion
What else is associated with heart failure?
Pulmonary edema
Pleural effusions
What are the effects of liver failure?
Edema
Ascites
Part 1
Why do patients with liver failure get edema?
(specific to a particular protein mechanism)
With liver failure, the liver fails to produce normal byproducts.
Liver is responsible for producing ALBUMIN
WIth LESS albumin, means more leaky fluid!
Part 2
Why do patients with liver failure get edema?
Second mechanism
Portal hypertension
leads to ascites
What are the two methods of getting edema through liver failure?
- Decreased production of albumin
- Portal hypertension
What are the two ways renal disease can cause edema?
-Retained sodium and water (leads to increased intravascular hydrostatic pressure)
-Nephrotic syndrome (excess protein loss in urine leads to decreased oncotic pressure)
Can you guess what is happening here?
Protein deficiency (Kwashiorkor)
Insufficient albumin (reduced plasma oncotic pressure)
Not enough protein ingested : malnutrition
Not enough protein produced : liver failure
Too much protein lost: kidney disease with nephrotic syndrome
This is image represents what type of edema?
Lymphatic obstruction
Can you give a few examples of what would cause localized lymphedema?
Infection
Inflammation
Trauma
Tumors
Surgery
Malformations
You have identified your patient is releasing exudate. What is most likely causing this protein rich fluid to escape?
Sepsis
Inflammation
Burns
*All three of these lead to increased vascular permeability
What is this histologic slide showing?
Pulmonary edema
*Notice how SOME of the alevolar spaces are filled with air, and others have a pink tinge to them. ALL of the alveolar spaces SHOULD be filled with air. The pink spaces are abnormal fluid accumulation
What are these slides revealing?
Name the cells!
CHRONIC Pulmonary edema
*hallmark: chronic congestions shows an increase in hemosiderin-laden macrophages “heart failure cells”
Hepatic congestion is due to the obstruction/flow reduction of the ______________
Central vein
What is this gross specimen revealing?
“Nutmeg liver”
Shows the pathology of chronic hepatic congestion
Dark areas=dying hepatocytes
What is the initial step in hemostasis?
Reflexive vasoconstriction
Why is neurogenic reflexive vasoconstriction an effective first step in hemostasis?
- Reduces blood flow to the area so you don’t bleed as much!
- Reduces the surface area of the affected area to allow hemostasis to occur
What is the “goal” of primary hemostasis?
Formation of a Platelet Plug
Weibel palade bodies are useful indicators of what cells?
They are a significant source of?
Endothelial cells
vWF
What happens if you have a deficiency in vWF?
Von Willebrand Disease
Inability of platelets to stick down, Platelet adhesion will not occur
What happens if there is a deficiency in Gp1b receptor?
Bernard Soulier Syndrome
Platelet adherance disorder
How can you morphologically identify the difference between Von Willebrand disease and Bernard Soulier syndrome?
Bernard Soulier syndrome will have morphological defects in the platlets themselves!
That’s because receptor Gp1b is ON THE PLATELETS
*ON THE RIGHT=Bernard Soulier syndrome platelets, HUGEEEE platelets
What occurs during platelet activation?
After adhesion…
Conformational change
(-) Negatively charged surface
GpIIb-IIIa change and create fibrinogen links
Secretion initiated by thrombin, release of ADP and Thromboxane A2
What does aspirin inhibit?
Why does that make sense?
Thromboxane A2
Blocking platlet aggregation
What occurs during the third step in primary hemostasis?
Aggregation
Describe what happens during aggregation in primary hemostasis?
Conformational change in the GpIIb-IIIa complex in activated platelets allow for bivalent binding of fibrinogen and subsequent cross-linking
What is the name of the disease associated with a deficiency of GpIIb-IIIa?
Glanzmann Thrombasthenia
How do we know if something is wrong with primary hemostasis?
What are the clinical questions we can ask?
Nose bleeds?
Oral bleeding with teeth brushing?
Easy bruising?
Heavy menstrual cycle?
What are the laboratory methods to determine there is something wrong with primary hemostasis?
Bleeding time (outdated)
Platelet function studies (outdated)
PFA 100 (modern)
Flow cytometry (modern)
Thrombocytopenia
Mechanism?
Platlet count?
Platelet adhesion?
Platelet aggregation?
Mechanism = loss or impaired production of platlets
Platlet count= LOW
Platelet adhesion= YES
Platelet aggregation= YES
Von WIllebrand disease
Mechanism?
Platlet count?
Platelet adhesion?
Platelet aggregation?
Mechanism= Inherited lack of vWF
Platlet count= Normal
Platelet adhesion= NO
Platelet aggregation= YES
Bernard-Soulier disease
Mechanism?
Platelet count?
Platelet adhesion?
Platelet aggregation?
Mechanism= Abnormal GpIb
Platelet count= Normal
Platelet adhesion= NO
Platelet aggregation= YES
Glanzmann’s Thrombasthenia
Mechanism?
Platelet count?
Platelet adhesion?
Platelet aggregation?
Mechanism= Abnormal GpIIb-IIIa
Platelet count= Normal
Platelet adhesion= YES
Platelet aggregation=NO
Generally, what are the three steps of primary hemostasis?
Adhesion
Activation/secretion
Aggregation
What is the goal of secondary hemostasis?
Forming a fibrin clot
Draw the coagulation cascade with the intrinsic and extrinsic pathway
What does aPTT measure?
WHat does PT measure?
aPTT = intrinsic pathway clotting time
PT = extrinsic pathway clotting time
Aliases for clotting cascade:
What is the name of Factor I? Ia?
I =Fibrinogen, Ia=Fibrin
*activated form is (a)
Aliases for clotting cascade:
What is the name of Factor II? IIa?
II= Prothrombin, IIa=Thrombin
Aliases for clotting cascade:
What is the name of Factor VIII?
Antihemophilic A Factor (AHF)
What are the vitamin k-dependent factors?
II
VII
IX
X
How does coumadin work?
Blocks the formation of active Vitamin K
By doing this, you knock out factors II, VII, IX, X
THEN you don’t clot as much!
What are the three major functions of Thrombin?
- Stabilizes fibrin
- Activates platelets
- Activates receptors on inflammatory cells and endothelium
What are the dermatologic manifestations of a defect in hemostasis?
(A) Petechiae (small)
(B) Purpura (larger)
(C) Ecchymosis (palpable)
What is a disease that is commonly associated with factor deficiencies?
Hemarthrosis
Bleeding into a joint space
What is the last step in secondary hemostasis?
STOPPING IT!
Fibrinolysis and limitation of clot formation
- Arrest in clot formation
- Resorption of clot
- Tissue repair
What is the body’s endogenous clot dissolver?
Plasmin
What activates plasmin?
t-PA
What are three endothelium factors that inhibit platelets?
Adenosine diphosphatase
Prostacyclin
Nitric oxide
What mechanism in the endothelium turns off coagulation?
When Thrombin sees a normal and healthy endothelial cell, it binds to the receptor thrombomodulin. This creates activated protein C which TURNS OFF COAGULATION
What are ALL the vitamin-k dependent factors?
II
VII
IX
X
Protein C
Protein S
Define a:
Thrombus
Embolus
Thrombus: Occlusion
Embolus: Traveling occlusion
What is Virchow’s tirad?
Risk factors associated with Thrombosis
Virchow’s triad part 1:
Describe what happens when you damage the endothelium?
Endothelium becomes PROTHROMBOTIC
Virchow’s triad part 2:
What happens with alterations in blood flow?
Turbulent blood flow is BAD
Can feed into endothelial injury as well!!!
Virchow’s tirad part 2:
What happens with alterations in blood flow?
Internal obstructions, compressions, inadequate heart chamber function, aneurysm, hemorrhoids can all contribute to
formation of a thrombus
Virchow’s triad part 3: Hypercoagulability
What are the primary genetic causes?
Deficiency of antithrombotic factors:
- Antithrombin (III) deficiency)
- Protein C deficiency
- Protein S deficiency
Increased prothrombotic factors:
- Factor Va
- Prothrombin
What are the secondary (acquired) causes of hypercoagulability?
Prolonged bed rest/immobilization
MI
Cancer
A fib
What are the ways a DVT can present?
What are you most concerned about a DVT embolus dislodging?
Pulmonary embolism
Read pages 123-125 of robbins per Dr. Singh
Genetic:
Factor V Leiden mutation
Aquired:
Heparin-induced thrombocytopenia
Antiphospholipid antibody syndrome
What is the mechanism of action of factor V leiden mutation?
Mutation in factor V that makes it resistant to cleavage by protein C
Therefore….cannot turn off coagulation
How can you test for Factor V Leiden mutation?
Direct genetic testing
or
APC resistance testing
How to suspect primary hypercoagulable states?
An initial event occured: DVT, PE
No provoking factors
Young age <40
Strong family history
What is Heparin-induced thrombocytopenia?
AQUIRED Hypercoagulable state
Prothrombotic state caused by antibodies to PF4-heparin
What is Antiphospholipid antibody syndrome?
Aquired Hypercoaguable state
Antibodies against plasma proteins that bind to phospholipids
What are lines of zahn?
Pathologic finding that indicates a thrombus/embolus occurred during active blood flow
(during the patient’s life)
What are the 5 types of emboli we discussed in lecture?
- Thromboemboli (blood clot)
- Fat/marrow emboli
- Air emboli
- Septic emboli
- Amniotic fluid emboli
Describe a :
Fat Emboli
Caused by a fracture or soft tissue trauma
BONE MARROW/(fat) is introduced into circulation
*frequently seen as a post mortem finding due to resuscitation prior to demise
What are common causes of Air embolism?
Cardiac catheterization
Deep sea diving! The Bends, “Caisson disease”
What is an Amniotic fluid embolism?
More of a severe anaphylactic response to amniotic fluid
Sudden dyspnea, cyanosis, shock, subsequent pulmonary edema
What is endocarditis?
Heart valve has become infected
Infective vegetations break off and manifest in other sites
What are the peripheral manifestations of endocarditis?
Skin microemboli: Janeway lesions (purpuric)
Retinal microemboli : Roth spots
Vascular damage in nail bed: Splinter hemorrhage
Read infarct section
Robbins pages 129-130
What is a white thrombus?
ARTERIAL
Platelet rich
Occur in high shear stress
ARTHEROSCLEROSIS
Coronary, cerebral arteries
What is a red thrombus?
Venous
Red cell rich
Occurs during STASIS
Lower extremities
What are disease that occur when white thrombi collect?
Strokes
Heart attacks
What is the definition of shock?
Tissue oxygen and nutrient delivery is inadequate to meet physiologic needs
