Lecture | Part 2 Hemodynamic disorder Flashcards
- EXTRAVASATION beyond vessel
- “HEMORRHAGIC DIATHESIS”
- HEMATOMA (implies MASS effect)
- “DISSECTION”
- PETECHIAE (1-2mm) (PLATELETS)
- PURPURA <1cm
- ECCHYMOSES >1cm (BRUISE)
- HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS
- ACUTE, CHRONIC
hemorrhage
manifestations on hemorrhage:
very small 1 to 2 mm millimeters
petechiae
manifestations on hemorrhage:
little larger than petechiae
purpura
manifestations on hemorrhage:
large areas with hemorrhage more than 1 centimeters
ecchymoses or bruise
blood in the thorax
hemothorax.
blood in the pericardial space
hemopericardium
blood in the peritoneal space
hemoperitoneum
blood in the joint spaces
hemarthrosis
from acute to chronic so blood may be manifest as color
BROWN or red brown
from hemoglobin it will be transformed into bilirubin and eventually become
hemosiderin.
timing of lesion where how many days are the lesion present. Helps in the evolution of hemorrhage through
change in the type of pigments through time
hemorrhage in the head
epidural hematoma or subdural
one of the layers of your meaninges– covering of your brain
dura
means above the dura
epi
means down or under so under the dura
subdural
follows skull fracture
epidural
follows close head trauma
subdural hematoma
have texture and usually ADHERE to a vessel wall.
Pre-mortem clots
have a jelly or chicken fat consistency.
Post-mortem clots
opposite of thrombosis
hemostasis
- PRESERVE LIQUIDITY OF BLOOD
- “PLUG” sites of vascular injury
hemostasis
3 components of hemostasis
- VASCULAR WALL
- PLATELETS
- COAGULATION CASCADE
One important or fundamental aspect on blood
it should be in a liquid state
thrombus formation is usually needed ?
- when there are vascular injury
- thrombus is used to plug the blood vessel injury
to achieve this hemostasis there are three important factors or participants
- vascular wall
- platelets
- coagulation cascade
- Reflex Neurogenic
- Endothelin, from endothelial cells
ARTERIOLAR VASOCONSTRICTION
- Adhere and activate platelets
- Platelet aggregation
THROMBOGENIC ECM at injury site
Adhere and activate platelets
TISSUE FACTOR released by endothelium activates coagulation cascade to form
thrombin
first reaction in vascular injury
arteriolar vasoconstriction
exposure of the sub
endothelial matrix is called
thrombogenic
cause platelets to activate and adhere to each other called platelet aggregation
thrombogenic
1° hemostasis
platelet aggregation
a plug that is considered a soft blood because it is composed mainly of platelets
primary hemostasis
tissue factor activates the
coagulation cascade
tissue factor activates the coagulation cascade resulting to
thrombin formation
the purpose of thrombin in tissue factor is to form
fibrin
1° Hemostasis
fibrin
polymerizes the platelet plug–makes it
more durable and makes it quite hard
fibrin
plug that is acted upon by fibrin make it stronger
secondary plug
when the blood vessel wall is already repaired, the fibrin plug or what you call secondary plug will be
lyse
players that participate in thrombus formation
- Endothelium
- Platelets
- Coagulation “Cascade”
–?– formation is not in response to the blood vessel injury but to abnormalities and pathogenic
thrombus
normal endothelial properties
- Antiplatelet properties
- Anticoagulant properties
- Fibrinolytic properties
in injury of endothelium secretes
Pro-coagulant properties
in injury the endothelium will secrete pro-coagulant properties and trigger
coagulation cascade
- Protection from the subendothelial ECM
- Degrades ADP (inhibit aggregation)
ANTI-Platelet PROPERTIES
- Membrane HEPARIN-like molecules
- Makes thrombomodulin which is used for synthesis of
protein c - tisse factor pathway inhibitor
ANTI-Coagulant PROPERTIES
protein c has what type of property
anti-thrombin
makes vWF, TISSUE FACTOR, & Plasminogen inhibitors
PROTHROMBOTIC PROPERTIES
binds Platelets→Collagen
vWF
in injury, endothelium will be prothrombotic and enhanced formation of thrombus due to
Von Willibrand factor
factor that binds platelets to the sub endothelial matrix
Von Willibrand factor
PROTHROMBOTIC PROPERTIES of endothelium is activated by
Infectious agents, Hemodynamics, & Plasma
Alpha granules
- Fibrinogen
- Fibronectin
- Factor-V, Factor-VIII
- Platelet factor 4, TGF-beta
Delta granules (dense bodies)
ADP/ATP, Ca+, Histamine, Serotonin, Epinephrine
platelet phases
- Adhesion
- Secretion (I.e., “release” or “activation” or “degranulation”)
- Aggregation
platelet adhesion is regulated by
Von Willebrand factors
during platelet adhesion, this bridges the receptors in the platelet surface through the extracellular matrix collagen
Von Willebrand factors
in the subendothelial layer, this will be exposed upon injury
in the sub endothelial layer this will be exposed upon injury
Primarily to the subendothelial ECM
platelet adhesion
the release of the substances found in the alpha and delta granules of the platelets
platelet secretion
Binding of agonists to platelet surface receptors and intracellular protein PHOSPHORYLATION
platelet secretion
substances that will enhance platelet aggregation
ADP and thromboxane a2
platelet events
- ADHERENCE to ECM
- SECRETION of ADP and TXA2
- EXPOSE phospholipid complexes
- Express TISSUE FACTOR
- PRIMARY SECONDARY PLUG
- STRENGTHENED by FIBRIN
formation of thrombus which is emphasized will now be abnormal in a
disease condition; pathologic condition because there is blood clot formation
1.INTRINSIC(contact)/EXTRINSIC(Tissue Factor)
2. Proenzymes→ Enzymes
3. Prothrombin(II)→Thrombin(lla)
4. Fibrinogen(1)→Fibrin(la)
5. Cofactors
- Ca++
- Phospholipid (from platelet membranes)
- Vit-K dep. factors
coagulation cascade
Vit-K dep. factors:
II, VII, IX, X, Prot. S, C, Z
triggered when there is release of your tissue factor
coagulation cascade
enhances the cascade
coagulant properties
coagulation cascade inhibitors in the presence of
1.protein c
2. protein s
3. anti-thrombin
4. plasminogen inhibitors
checks for your intrinsic pathway
activated protrumbin time
will look at your extrinsic pathway
protrumbin time
check the number of platelets
Bleeding time
Platelet-count
150,000-400,000/mm3
Bleeding time checks the number of platelets for how many mins
2-9min
- Pathogenesis
- Endothelial Injury
- Alterations in Flow
- Hypercoagulability
- Morphology
- Fate
- Clinical Correlations
- Venous
- Arterial (Mural)
thrombosis
person is prone to thrombus formation because of this abnormalities contributed by these three factors
- one is endothelial injury
- the other one is abnormalities in the flow of blood
- and the third one is a hypercoagulability state
Thrombosis will occur due to Virchow’s triangle which are the
- endothelial injury
- abnormal (non-laminar) flow
- hyper-coagulation
any perturbation in the dynamic balance of the pro- and antithrombotic effects of endothelium, not only physical “damage”
ENDOTHELIAL “INJURY”
disruption on the laminar flow of blood will bring the platelets
platelets into contact with the endothelium and or the extracellular matrix
two forms of hypercoagulability
inherited & acquired
most common inherited hypercoagulability
Factor V and Prothrombin defects
common inherited hypercoagulability are mutation in
prothrombin gene & methyltetrahydrofolate gene
rare inherited hypercoagulability
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
Very rare inherited hypercoagulability
Fibrinolysis defects
- Prolonged bed rest or immobilization
- Myocardial infarction
- Atrial fibrillation
- Tissue damage (surgery, fracture, burns)
- Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis)
- Prosthetic cardiac valves
- Disseminated intravascular coagulation
- Heparin-induced thrombocytopenia
- Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
acquired hypercoagulability
Risk for thrombosis:
- Cardiomyopathy
- Nephrotic syndrome
- Pregnancy
- Oral contraceptive use
- Sickle cell anemia
- Smoking, Obesity
thrombosis morphology adherence to vessel wall, such as
- HEART (MURAL)
- ARTERY (OCCLUSIVE/INFARCT)
- VEIN
most important thing to remember that has clinical outcome of a thrombus formation
OBSTRUCTIVE vs. NON-OBSTRUCTIVE
thrombosis color
RED, YELLOW, GREY/WHITE
mural thrombus in the heart can be found in
chambers or valves of the heart
an example of an obstructive form of thrombus
mural thrombus
fate of thrombi
- PROPAGATION (Downstream)
- EMBOLIZATION
- DISSOLUTION
- ORGANIZATION
- RECANALIZATION
add up more cluttered blood along its
way
Propagation
formation of small lumen within the thrombus that can make the blood pass through
recanalization
the thrombus dissolved and almost get there’s no remnantsthat can be seen
resolution
thrombus become part of the wall; it’s incorporated into the blood vessel wall
organize
thrombus that occurs in the arteries, there is a complete seal off on the blood vessel so blood cannot pass through anymore
occlusive arterial thrombus
DVT
deep vein thrombosis
CHF is a huge factor and fairly common occurrence and it is due to inactivity
deep vein thrombosis
dvt is usually trauma, surgery, burns, injury to vessels, and there is prolonged immobilization to the
lower leg (calf, thigh, pelvic)
Procoagulant substances from tissues and Reduced t-PA activity
deep vein thrombosis
old atherosclerosis + fresh thrombosis
ACUTE MYOCARDIAL INFARCTION
ARTERIAL THROMBI also may send fragments in what direction
DOWNSTREAM
ARTERIAL THROMBI also may send fragments that may contain
flecks of PLAQUE
PROPORTIONAL to the % of cardiac output the organ receives,
LODGING
not a primary disease and considered as complications to obstretic complications, difficult child birth, in advanced malignancies, and shock.
Disseminated intravascular coagulation
Disseminated intravascular coagulation is a serious condition due to
consumptive coagulopathy
prone to bleeding. An example are reduced platelets, fibrinogen, F-VIII and other consumable clotting factors, brain, heart, lungs, kidneys, MICROSCOPIC ONLY
consumptive coagulopathy
other materials that can act as an embolus
fat globules, bubbles of air, amniotic fluid, and tumor cells
type of embolus it is usually fatal
saddle type
consistency of cluttered blood when the patient is still alive
pre-mortem blood clot : Friable, adherent, lines of ZAHN
consistency of cluttered blood when the patient is dead
post mortem blood clot : Current jelly or chicken fat, not adherent
most common source of pulmonary embolism
thrombus from the deep veins of the legs
embolism involves the lungs, usually silent, there’s no premonition and you develop chest pain and have shortness of breath that can cause sudden death
pulmonary embolism
- “PARADOXICAL” EMBOLI
- 80% cardiac; 20% aortic
SYSTEMIC EMBOLI
Embolization lodging site is proportional to the degree of flow (cardiac output) that area or organ gets, i.e., brain, kidneys, legs
SYSTEMIC EMBOLI
based on the proportional degree of the flow of the cardiac output.
SYSTEMIC EMBOLI
emboli that carries the squames from the baby will penetrate the uterine blood vessels and lodge into the lungs of the mother during difficult childbirth
amniotic fluid
deep sea divers are
not advised to arise to the surface of the ocean rapidly due to this emboli
bubbles of air
fat along this may act as an embolus
long bone fractures
Defined as an area of necrosis secondary to decreased blood flow
infarction
INFARCTION FACTORS
- NATURE of VASCULAR SUPPLY
- RATE of DEVELOPMENT
- SLOW (BETTER)
- FAST (WORSE) - VULNERABILITY to HYPOXIA
- MYOCYTE vs. FIBROBLAST - CHFvs.NOCHF
3 cells that are vulnerable to hypoxia
- cardiac cells
- renal tubular cells
- neurons (brain cells)
death of tissues due to loss of blood supply
infarction
- Pathogenesis
- Cardiac
- Septic
- Hypovolemic - Morphology
- Clinical Course
shock
manifested as loss of tissue perfusion
Shock
collapse in the circulatory system such that there is a lack of blood flow to important organs
Shock
defines as cardiovascular collapse
shock
common pathophysiologic features of shock
- INADEQUATE CARDIAC OUTPUT
- INADEQUATE BLOOD VOLUME
general results of shock
- INADEQUATE TISSUE PERFUSION 2. CELLULAR HYPOXIA
- UN-corrected, a FATAL outcome
type of shock : Acute, Chronic Heart Failure
CARDIOGENIC
type of shock : Hemorrhage or Leakage
HYPOVOLEMIC
type of shock : “ENDOTOXIC” shock, #1 killer in ICU
SEPTIC
type of shock : loss of vascular tone
NEUROGENIC
type of shock : IgE mediated systemic vasodilation and increased vascular permeability
ANAPHYLACTIC
cardiogenic shock equates to
failure of the heart to pump adequate blood
equates to inadequate blood volume
hypovolemic shock
due to massive infection and activation of the inflammatory mediators resulting to low blood pressure
Septic shock
IgE
allergy-hypersensitivity reactions
cause systemic visodilatation; slowing down the flow of blood and there is increased vascular permeability.
anaphylactic shock
causes cardiogenic shock
- MYOCARDIAL INFARCTION
- VENTRICULAR RUPTURE
- ARRHYTHMIA
- CARDIAC TAMPONADE
- PULMONARY EMBOLISM (acute RIGHT heart failure or “corpulmonale”)
causes cardiogenic shock when there is an external force that constrict the pumping action of the heart oroutside force that impinged on the heart
Cardiac tamponade
causes cardiogenic shock when contraction of the heart is irregular
Arrhythmia
one of the most common causes of cardiogenic shock
myocardial infarction
caused by overwhelming infection and when gram-negative bacteria enter the blood that results to low blood pressure
Septic shock
polyclonal T-lymphocyte activators that induce systemic inflammatory cytokine cascades similar to those occurring downstream in septic shock
SUPERANTIGENS
- OVERWHELMING INFECTION
- “ENDOTOXINS”
- FUNGAL
- “SUPERANTIGENS
Septic shock
prime example of “toxic shock” antigens
Staphyloccoccus aureus
TOTAL BODY inflammatory response
Septic shock
Usually Gram-negative bacteria, Degraded bacterial cell wall products, Also called “LPS”, because they are Lipo- Poly-Saccharides, Attach to a cell surface antigen known as CD-14
ENDOTOXINS
clinical stages of shock
- NON-PROGRESSIVE
- PROGRESSIVE
- IRREVERSIBLE
clinical stage of shock known as compensatory mechanisms, action is done by catecholamine, and vital organ perfused
NON-PROGRESSIVE
clinical stage of shock known as acidosis, early organ failure, hypoperfusion, and oliguria
PROGRESSIVE
HEMODYNAMIC CORRECTIONS of no use
IRREVERSIBLE
cause acidosis and this is manifested in a low ph.
Lactic acid
Death of the cardiac cells because again lack of oxygen
myocardial necrosis
vulnerability of the renal tubular cells so it is manifested as oliguria; no formation of urine so it is an early or acute renal failure
acute tubular necrosis
simultaneous bleeding and thrombose formation
DIC
clinical progression of symptoms of shock
- Hypotension
- Tachycardia Tachypnea
- Warm skin →→ Cyanosis
- Renal insufficiency
- Obtundance
- Death
increase heart rate increase breathing
tachycardia