BLD 204 Exam 3

Repeated thrombi blocking coronary arteries

Which of the following would have the most serious clinical significance?

Activate platelet aggregation

Which of the following is a function of thrombosis

Causing endothelial injury

Which of the following is a way that turbulent blood flow can promote thrombosis?

Plasmin



(Degrades fibrin)

What molecule cleaves fibrin to dissolve clots?

1. Vasoconstriction

2. Platelet Plug

3. Coagulation Cascade

4. Secondary Hemostasis
(Stable clot formation)
(Thrombin: Cleaves Fibrinogen → Fibrin Clot AND Activates Platelets to reinforce plug)

5. Limitation of Clotting
(Fibrinolysis, TTPA, Plasminogen → Plasmin)

5 major components involved in hemostasis

hypovolemic

Type of shock caused by a large internal hemorrhage would be

Platelet aggregation

(follows platelet activation, binding of fibrinogen)

Which of the following happens as part of primary homeostasis

Activation

During what step of platelet plug formation do platelets change shape

Activation of the RAA system

Cardiac edema is related to ineffective pumping of the heart, but it is even more strongly influenced by what?

Increased vascular permeability

Jim has an allergic reaction to a new type of sterile gloves used in his lab. thankfully, only his hands are affected, but they are very swollen. what is the cause of this localized edema?

Progressive

At what stage of shock do metabolic problems emerge?

CRP

In the biochemical theory of fat embolism formation, what molecule causes the smaller fatty acids to accumulate into larger globules?

true

T/F: ischemia causes infarcts

Thrombi

(make up emboli)

Most clinically significant pulmonary embolism is cause by...?

lipid debris

What is found in the core of atherosclerotic plaque?

thin cap, large core

Which of the following would describe a vulnerable atheroma?

Accumulation of lipoproteins in intima

Which occurs FIRST in the development of an atherosclerotic plaque?

Atherosclerosis

__________is a chronic inflammatory response to endothelial injury

- tiny (1-2 mm) hemorrhages into skin, mucous membranes, or serosal surfaces,
- causes include low platelet counts, defective platelet function, and loss of vascular wall support, vitamin C deficiency

Petechiae

- slightly larger (3-5 mm) hemorrhages,
-Can result from same disorders as petechiae, as well as trauma, vascular inflammation and increased vascular fragility

Purpura

1. vWF activation of platelets
2. TF activation of Coagulation cascade
3. Plasminogen activator inhibitors

Pro-coagulatant functions of endothelium

1. Inhibit platelets by hiding ECM
2. Inhibit coag factors w/ heparin like molecules, thrombomodulin, and TFPI
3. Fibrinolysis: TTPA

Anti-coagulatant functions of endothelium

- larger (1-2 cm) subcutaneous hematomas (bruises),
- Extravasated RBC's are phagocytosed and degraded by macrophages; color changes of a bruise result from conversion of hemoglobin to bilirubin and eventually biliverdin

Ecchymosis

1. Activates platelet aggregation and endothelial cells
2. Generates fibrin
3. Activates leukocytes

List three functions of thrombin

1. Increased Hydrostatic Pressure INSIDE vessel
2. Increased Colloid Osmotic Pressure OUTSIDE vessel

What causes fluid to leave the vasculature

1. Plasma osmotic pressure
(from plasma proteins like albumin)
2. Selective permeability of endothelium
3. Tissue tension

What causes fluid to stay in the vasculature

Both are related to INCREASE blood flow in given tissue

Active Hyperemia: More blood in (increase traffic)

Congestion: Less blood out (construction)

Active hyperemia vs
Congestion (passive hyperemia)

Hyperemia and Congestion: blood is still confined within the vasculature

Hemorrhage: blood has escaped from the blood vessels

Hyperemia and Hemorrhage

filariasis

What disease below causes lymphedema by blocking the lymph vessels with parasites?

Edema

Abnormal accumulation of fluid in the extravascular compartment

Ascites

accumulation of fluid in the peritoneal cavity, causing abdominal swelling.

1. Increase in intracapillary pressure
2. Decrease in plasma oncotic pressure
3. Lymphatic obstructions
4. Retention of salt/water

Primary causes of edema

arteriolar vasoconstriction

occurs immediately and markedly reduces blood flow to the injured area

Transudates: Edema due to increased hydrostatic pressure or reduced intravascular protein

Exudates: Edema due to increased vascular permeability (ex. inflammation)

Transudates vs. Exudates

Gravity influences the distribution
Excess retention of Na+ and H2O by kidneys (large part)
Weak pumping leads to increase venous P (small part)

Cardiac Edema

Related to Na+ which increases H2O retention, Transudate

Heavy proteinuria from leaky capillaries →
Loss of albumin →
Decrease plasma oncotic pressure

Renal Edema (Nephritic and Nephrotic)

From prolonged starvation →
loss of fat →
decreased tissue tension →
space fills w/ fluid → edema

Nutritional Edema

Presents as ascites

↑ intracapillary P →
↓ albumin/oncotic P →
↑ hepatic lymph AND Na+ retention

Chronic liver damage

Increased intracapillary pressure
Causes: IV overload (main), severe anemia, renal failure, increase in altitude

Increase capillary permeability
Causes: ARDS, Aspiration, DIC, Pneumonia (infectious or chemical), Severe trauma, bacteremia

Pulmonary Systemic Edema

1. Increased hydrostatic pressure in the microcirculation
(Occlusive venous thrombosis → in venous system.
Build-up of pressure b/c blood not flowing)

2. Increased local vascular permeability
(Inflammation, Type I hypersensitivity/allergy)

3. Lymphedema
(Obstruction of the normal lymphatic flow due to surgery or inflammation or filariasis, ex. breast cancer)

3 types of disturbances in fluid distribution seen in local edema

Thrombosis: Hemostasis in the wrong place, wrong time
In healthy blood vessel

Clot: Good if it happens when there's damage to vascular tissue, bad when its in healthy blood vessel

Clots vs. Thrombi

Localized clot formation:
One spot/ non systemic
Normal product of coagulation cascade

Disseminated coagulation:
Clots where they shouldn't be, systemic
All coagulation factors used up leads to at risk for bleeding

Localized clot formation vs. disseminated coagulation

1. Changes in the intimal surface of vessel
2. Changes in the pattern of blood flow
3. Changes in the constituents of the blood

3 states in Virchow's triad

Platelets and WBC's contacting endothelium more than usual

Slowing movement of pro and anti coagulative agents

Stasis contributes to...

Aneurysms
Congestive cardiomyopathy
Myocardial infarct
Mitral valve problems

Stasis in heart vessels can cause...

General = Congestive heart failure
Local = leg thrombosis

General vs. Local vein thrombosis

More platelet-wall interactions, procoagulative factors (fibrinogen)

Decreased natural anticoagulants

Increased blood viscosity

Stasis

Procoagulant compounds form tumors

Hyper coagulable state risk factors

Factor V-Leiden mutation

Prothrombin mutation

Common inherited disorders w/ risk of thrombosis

Thrombosis

related to increase estrogen,

Increases fibrinogen, & Vit K clotting factors

Decreases antithrombin III

Oral contraceptives increase risk of...

Malignancy (tumors)
Nephrotic Syndrome
Obesity
Age
Smoking

Risks for thrombosis

1. Lysed by plasmin

2. Propagate

3. Form emboli (dangerous)

3 outcomes of thrombi

Abnormally increased tendency toward blood clotting (coagulation)

Platelets collect at branching points→
platelet-wall interaction→
inflammation

Causes issues such as atherosclerosis in the narrowed areas of arteries

Define hypercoagulable and relation to platelets

PDGF causes SM proliferation so thrombus in "buried" in intima

PDGF and thrombi

1. Pro inflammatory and hypofibrinolytic effects
2. V-Leiden mutation
3. Stasis or stagnation of blood in the veins.
4. Increase platelet activation
5. Overproduction of plasminogen activator inhibitor-1, inhibits fibrinolysis

How can obesity contribute to generation of thrombi?

1. risk factors on the arterial wall, decreased regular exercise, increasing immobility resulting in venous stasis, and increasing systemic activation of blood coagulation

2. Increases in coagulation proteins, specifically increased levels of factors VIII, IX and XI,

How can age contribute to generation of thrombi?

Leads to endothelial injury and dysfunction

Oxidizing chemicals and nicotine responsible for endothelial dysfunction.

Produces a chronic inflammatory state


Decreased HDL

How can smoking contribute to generation of thrombi?

- Make up 99% of emboli

- Thrombosis = blockage from a clot
(occlusion is any form of blockage)

- In a major vein → can cause deep vein thrombosis

- Embolus → travels until it blocks something or can lay across the side of the vessel (mural clot) and can maintain blood flow but there is long term damage to the blood vessel

Thrombi (difference from emboli)

1. 99% thrombus
2. blood clot
3. Air
4. Nitrogen
5. Fat
6. Chunks of bone marrow→ breaking rib cage/ sternum
7. Debris from atherosclerosis
8. Masses of tumor cells

State at least 8 materials that can cause or be incorporated in emboli

1. DVT: most come from your "kneepit"
2. Venous thrombus→ pulmonary arterial tree

Effects depend on:
Size of embolus
Congestion in the pulmonary circulation

Contributing factors to the development of pulmonary emboli

Massive (5%, sudden death)

Medium (10-15%, dyspnea/trouble breathing)

Small (60-80%, too small for problems)

3 categories of pulmonary emboli

Systemic:
Clots can lodge anywhere
Mainly in Brain, kidneys, leg, GI tract, spleen
Major blood source = Left side of the heart
Causes:
1. Atrial fibrillation- doesn't beat right
2. MI- ischemia
3. Congestive cardiomyopathy- weakened heart
4. Infective endocarditis- bacteria

Pulmonary:
Origin = Mainly "kneepit"
Placement = Lung

Systemic vs pulmonary emboli

Introduced to circulation through air by:
surgery: cardiac or brain
Chest injury
Fallopian tubes in exploration of sterility
Interference with the placenta

Clinically a lot like massive pulmonary embolisms

Explain how gaseous emboli are formed

Sources:
Long bone fractures
Severe burns
Severe soft tissue trauma "crushing"
Ischemic bone marrow necrosis (sickle cell disease)
Cardiopulmonary bypass surgery
Acute pancreatitis
Certain orthopedic procedures
Can occur in the absence of trauma
CRP can form them from stress

Explain how fat could become an embolus

Localized necrosis over an area
Caused by ischemia

Infarct

Reduced blood supply to the area
Blood flow is less than the tissue metabolism required
Usually localized perfusion problem

Ischemia

Arterial obstruction

Venous occlusion

Capillary obstruction

Causes of local ischemia

Functional:
Pain upon exertion (DVT)
Eventual cellular damage leads to more functional loss
1. Cell loss, Abnormal function, Lose vision, confusion, loss of function of body parts

Structural:
Necrosis results, can be patchy or massive
1. Usually coagulative but brain is liquefactive
2. Can become an abscess if microbes have access to the area, i.e. gut
Fibrous tissue when healed

Describe the functional and structural evidence of ischemia

Brain → liquefactive
All other major sites of infarct → coagulative

Types of necrosis

primary homeostasis

formation of the platelet plus. disruption of endothelium exposes sub endothelial von Willebrand factor and collagen-promoting platelet adherence and activation

"Widespread ischemia"

Characterized by systemic underperfusion due to prolonged diminished cardiac output or reduced blood volume

Development of shock

Hypovolemic:
reduced blood

Cardiogenic:
"heart attack"

Septic:
Systemic immune response due to microbial infection
Gram positive > gram negative > fungi
Results in arterial vasodilation and venous pooling

Types of shock

PAMPS recognition→
cell activation→
TNF, IL-1→ ROS, AA metabolites, complement→ inflammation→
systemic vasodilation→
endothelial cell activation→
tissue hypoperfusion, not enough blood because dilated, slower flow→
hypercoagulation/ DIC→
suppressed cell and tissue function→
hypoperfusion and multiple organ dysfunction

Progression of septic shock

dramatic shape change and release of secretary granules

activation of platelets result in what?

arteriosclerosis: hardening of ARTERIES

atherosclerosis: hardening of vascular wall

Arteriosclerosis and Atherosclerosis

Age
Gender (males>females)
Genetics

Atherosclerosis risk factors

aggregation to form a primary hemostatic plug

primary homeostasis secretes products from additional platelets that cause what?

deposition of fibrin

secondary hemostasis

tissue factor

vascular injury exposes _______ at the site of injury; a membrane bound procoagulant glycoprotein that is normally expressed by sub endothelial cells in the vessel wall, such as smooth muscle cells and fibroblasts

factor VII

in secondary homeostasis, tissue factors bind and activate which factor number ___ which sets in motion a cascade of reactions that culminates in thrombin generation

fibrin

thrombin cleaves circulating fibrinogen into insoluble _____, creating fibrin meshwork, and also a potent activator of platelets leading to additional aggregation at site of injury

permanent plug

in clot stablizagtion and respiration, polymerized fibrin and platelet aggregates undergo contraction to form a solid, __________ the prevents future hemorrhage

endothelial cells

what are central regulators of homeostasis?

t-PA and thrombomodulin

expression of which two tissue plasminogen activators confine the hemostatic process to the site of injury?

platelet adhesion

mediated largely via interactions with vWF, which acts as a bridge between the platelet surface receptors GpIb and exposed collagen

change shape and secrete granule contents

after platelet adhesion, platelets do what? this is also known as platelet activation

thrombin and ADP

platelet activation is triggered by which coagulation factors?

glanzmann thrombasthenia

deficiency of GpIIb

bernard-soulier syndrome

deficiency of GpIb

von willebrand disease

deficiency of von willebrand factor

hydrostatic pressure

the pressure that blood exerts on the vessel

plasma colloid osmotic pressure

the pressure exerted by different concentrations of molecules on the inside and outside of the vessel

interstitial fluid pressure

the pressure exerted by the fluid in the interstitial spaces outside the vessel

increased hydrostatic pressure, increased colloid osmotic pressure in the extravascular compartment

what causes fluid to leave the vasculature?

osmotic pressure like albumin, tissue tension and selective permeability of endothelium

what helps fluid remain in the vasculature?

lymph system

normal net loss from the vasculature returns through where?

vascular wall, platelets and coagulation cascade

three elements of hemostasis

ECM

damage to the endothelial layer exposes ______

adhesion, activation, aggregation

platelet plus facilitates platelet ______, ______ and ______

primary hemostasis

the formation of the initial platelet plug is called ______?

thrombin activation

tissue factor + factor VII = ?