Module 6 - Disturbed Blood Flow

Question 1

What do cells and tissues depend on to survive?

Answer 1

Survival of cells and tissues is dependent on the oxygen provided in the blood supply as well as on a normal fluid balance.

Question 2

Under normal conditions, as blood passes through capillary beds…

What can disturb this?

Answer 2

Proteins in the plasma are retained within the vasculature and there is little net movement of water and electrolytes into the tissues

This balance can be disturbed by pathologic conditions that alter endothelial function, increase vascular hydrostatic pressure, or decrease plasma protein content, all of which promote edema — the accumulation of fluid in tissues resulting from a net movement of water into extravascular spaces

Question 3

The structural integrity of blood vessels is frequently compromised by?

Answer 3

Trauma

Question 4

What is hemostasis?

Answer 4

Hemostasis is the process of blood clotting that prevents excessive bleeding after blood-vessel damage

Question 5

What occurs if there is inadequate hemostasis?

What if there is inappropriate clotting (thrombosis) or migration of clots (embolism)?

Answer 5

Inadequate hemostasis may result in hemorrhage, which can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death.

Inappropriate clotting (thrombosis) or migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction).

Question 6

60% of a persons body weight water is:

Answer 6

• 40% intracellular
• 15% interstitial
• 5% plasma

Question 7

Define edema:

Answer 7

Accumulation of abnormal fluids in the interstitial / intercellular tissue → swelling of the
subcutaneous tissues.

Question 8

Edema: What does normal control mechanism depend on?

Answer 8

1) Starling’s Law

2) Local Factors
- Lymphatic obstruction
- Vascular permeability

3) Permeability Factors
- Cardiovascular function
- Overall fluid balance
- Salt retention

Question 9

Edema:

• What is sterlings law?
• What are the 4 forces?
• Describe what occurs

Answer 9

Movement of fluid between vessels and tissue is governed by the balance between 4 forces:

1) Hydrostatic pressure in vessel which measures:
- 32 mmHg at arterial end
- 12 mmHg at the venous end

2) Oncotic pressure = Colloid osmotic pressure (COP) of plasma (26 mmHg) which reflects the
amount of serum protein (albumin).

3) Interstitial pressure (tissue tension) = 3-4 mmHg.
4) Tissue fluid osmotic pressure (very low).

Fluid movement between the vascular and interstitial spaces is governed mainly by two opposing forces—the vascular hydrostatic pressure and the colloid osmotic pressure produced by plasma proteins.

• Normally, the outflow of fluid produced by hydrostatic pressure at the arteriolar end of the microcirculation is nearly balanced by inflow at the venular end owing to slightly elevated osmotic pressure; hence there is only a small net outflow of fluid into the interstitial space, which is drained by lymphatic vessels.
• Either increased hydrostatic pressure or diminished colloid osmotic pressure causes increased movement of water into the interstitium.

Question 10

Edema will occur when there is:

• 4 factors
• give clinical examples

Answer 10

1. An increase in intravascular hydrostatic pressure: due to increased venous pressure - Clinical examples:
   a. congestive heart failure: Right side failureperipheral edema or Left side failurelung edema
   b. deep venous thrombosis of lower legs (local edema due to increased intravascular pressure)
2. A fall in colloid osmotic pressure of plasma: due to hypoproteinemia - Clinical examples:
   a. Liver disease as cirrhosis (liver failure): decrease synthesis of albumin
   b. Renal failure: loss of albumin in urine
   c. Malnutrition
3. Lymphatic obstruction: accumulation of interstitial fluid because of insufficient reabsorption and deficient removal of proteins, the latter increasing the oncotic pressure of the fluid in the interstitial space - Clinical examples:
   a. cancer
   b. inflammation
   c. postsurgical lymphedema
4. Sodium retention: causes both increase in hydrostatic pressure and reduced vascular osmotic pressure - Clinical examples:
   a. kidney diseases

Question 11

What 2 types are edemas classified into?

Answer 11

1. Localized edema - occurs due to:
   i) increased hydrostatic pressure due to vascular obstruction (local).
   ii) Lymphatic obstruction: compression by tumor or inflammation (local).
2. Generalized edema - occurs due to:
   i) increased hydrostatic pressure: i.e. heart failure.
   ii) decreased oncotic pressure (colloid osmotic pressure) due to:
   - loss of albumin in renal failure.
   - decreased synthesis of albumin (liver failure).
   iii) Sodium retention → Kidney disease.

Question 12

What is the definition of transudate vs. exudate?

Answer 12

Transudate

• Results from disturbances in Starling forces
• Protein<3g/dl
• Specificgravity<1.012

Exudate

• results from damage to capillary wall (recall Inflammation and inflammatory exudate)
• Protein>3g/dl
• Specific gravity>1.020

Question 13

What does normal hemostasis comprise of? What is thrombosis?

Answer 13

Normal hemostasis comprises a series of regulated processes that result in the formation of a blood clot that limits bleeding from an injured vessel

The pathologic counterpart of hemostasis is thrombosis, the formation of blood clot (thrombus) within non-traumatized, intact vessels.

Question 14

What is the definition of thrombosis?

Answer 14

Definition: formation of mass (clotted blood) in the heart or blood vessels. The mass is called a “thrombus” and it consists of:

• Red blood cells
• White blood cells
• Platelets
• Fibrin

Question 15

What are the primary abnormalities that lead to intravascular thrombosis?

Answer 15

(1) endothelial injury
(2) stasis or turbulent blood flow, and
(3) hypercoagulability of the blood (the so-called “Virchow triad”).

Question 16

What are three causes of thrombosis?

Answer 16

1. Vessel wall damage/alteration:
   - injury → tear
   - inflammation
   - endothelial activation / alteration can be produced by diverse exposures, including physical injury, infectious agents, abnormal blood flow, inflammatory mediators, metabolic abnormalities, such as hypercholesterolemia or homocystinemia, and toxins absorbed from cigarette smoke.
2. Changes in blood flow:
   - turbulence (in an aneurysm or
   at site of arterial branching)
   - stasis (slow circulation).
   - lack of activity
   - decreased cardiac output.
   - increased blood viscosity.
3. Changes in blood composition (hypercoagulability):
   - ↑ platelets
   - “Hypercoagulability” refers to an abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors. Can be due to genetic (rare) abnormalities or acquired (more common) conditions. In the latter for instance, prolonged bed rest or immobilization increases risk (see Table 4.2 in text and this week’s Case Study).

Question 17

What are 4 outcomes of thrombosis?

Answer 17

• Can increase in size and obstruct vessels.
• Can breakdown and form emboli.
• Can dissolve or be lyzed by fibrinolytic activity
• Can become organized and may recanalize.

Question 18

What are 2 complications of thrombi?

Answer 18

1) Fragments of thrombus break off and result in thrombo-embolization / emboli
2) Reduced blood flow to a tissue/organ resulting in ischemic injury or infarction.

Question 19

What is the definition of an embolism?

Answer 19

Occlusion of a blood vessel by a mass (embolus) transported to the site through the
blood stream (may be solid, liquid or gas).

Question 20

What are embolisms derived from?

- Common vs. non common

Answer 20

The vast majority of emboli derive from a dislodged thrombus - a thromboembolism.

Less commonly, emboli are composed of fat droplets, bubbles of air or nitrogen, atherosclerotic debris (cholesterol emboli), tumor fragments, bits of bone marrow, or amniotic fluid. Inevitably, emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion; depending on the site of origin, emboli can arrest anywhere in the vascular tree.

Question 21

What is the primary consequence of systemic embolization?

Answer 21

Ischemic necrosis (infarction) of downstream tissues.

Question 22

What are most (60-80%) pulmonary embolisms?

- With time?

Answer 22

Small and clinically silent

- with time, they undergo organization and become incorporated into the vascular wall.

Question 23

At the other end of the spectrum, a large embolus that blocks a major pulmonary artery can cause?

Answer 23

Sudden death

Question 24

What are types of embolisms?

Answer 24

1) Thrombi (termed a thromboembolus)
- The most common type of emboli
- Thromboemboli arise from thrombi and range in size from microscopic to those
which are large enough to occlude major arteries
- Thromboemboli may occur in either arteries or veins

2) Gas (air) = gas bubbles in divers; may be accidentally introduced during invasive procedures
3) Fat = often after fracture of large bones
4) Tumor

Question 25

What is ischema? Results in?

Answer 25

Due to: Inadequate blood supply to an area of tissue.

The result is: Infarction → area of necrosis (death) produced by ischemia.

Question 26

What are 2 causes of ischemia?

Answer 26

1) Decreased blood supply: (inadequate cardiac output).
2) Obstruction of blood vessel by:
o thrombus
o embolus
o pressure (outside pressure) o damage of the vessel wall:
→ inflammation

Question 27

What are the effects of ischemia?

- What does it depend on?

Answer 27

1) no effects → if there is alternate blood supply.
2) tissue death (infarction) → if severe and complete.

Depends on degree of the ischemia

Question 28

What can be said of ischemia and infarctions?

• How does this occur?
• What follows?
• What can be regenerated in some tissues?
• What are most infarcts replaced with?

Answer 28

In most tissues, the main histologic finding associated with infarcts is ischemic coagulative necrosis (Module 2 - Cell Injury and Death).

• An inflammatory response begins to develop along the margins of infarcts within a few hours and usually is well defined within 1 to 2 days.
• Eventually, inflammation is followed by repair, beginning in the preserved margins (Module 3 - Inflammation and Repair).
• In some tissues, parenchymal regeneration can occur at the periphery of the infarct, where the underlying stromal architecture has been spared.
• Most infarcts, however, are ultimately replaced by scar (fibrosis). The brain is an exception to these generalizations; ischemic tissue injury in the central nervous system results in liquefactive necrosis.

Question 29

What is white infarct vs. red infarct?

Answer 29

1) White infarct
◦ Arterial occlusion
◦ Solid organs as heart, spleen, kidney, brain
◦ Leg gangrene

2) Red infarct
◦ Venous or arterial occlusion
◦ Loose tissue as lung
◦ Dual blood supply
◦ Brain, intestine

Question 30

What is hemorrhage?

Answer 30

Hemorrhage (bleeding): a discharge or escape of blood from the blood vessels into the
surrounding tissues or to the exterior of the body or into a body cavity

Question 31

What causes a hemorrhage?

Answer 31

1) Trauma to large blood vessels due to surgical procedures or fracture

2) Weakened artery (from atherosclerosis, e.g. abdominal aortic aneurysm; congenital
weakness, e.g. berry aneurysm in Willis circulation

3) Infections (e.g. pulmonary tuberculosis)
4) Invasive tumors (erosion of vessel wall)
5) Hypertension (increase intraluminal blood pressure)

6) Hemorrhagic diatheses (spontaneous hemorrhage): affecting capillaries (small blood
vessels) including:
- Thrombocytopenia
- Severe decrease in number of platelets
- Deficiency of coagulation/clotting factors

Question 32

Define hematoma

Answer 32

accumulation of blood within the soft tissues

Question 33

Define Petechia

Answer 33

a pinpoint hemorrhage(s) (1-2 mm), usually in the skin; represent rupture
of capillaries or arterioles and mainly involving skin, mucous membranes and serosal
surfaces

Question 34

Define Purpura

Answer 34

diffuse, superficial hemorrhages in the skin, 3 to 5 mm

Question 35

Define Ecchymosis

Answer 35

a larger superficial hemorrhage (e.g. a ‘black’ eye); colloquially what we call
a ‘bruise’; skin discoloration reflects products of heme degradation from hemoglobin in the RBCs (enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown))

Question 36

Hemorrhage:

- Large bleeds?

Answer 36

Are described according to location:

a. Hemothorax / hemopericardium
- Collection of blood in the pleural cavities due to trauma or rupture of aorta
- Collection of blood in pericardial cavityaround heart due to rupture of heart or the aorta

b. Hemoperitoneum
- Collection of blood in the abdominal cavity due to rupture of an aortic aneurysm or
trauma to liver, spleen, or aorta

c. Hemoarthrosis
- Collection of blood in joint

Question 37

What is shock?

- Characterized by?

Answer 37

Shock is a state in which: diminished cardiac output or reduced effective circulating blood volume impairs tissue perfusion and leads to cellular hypoxia
- Characterized by failure of the circulatory system to maintain an appropriate blood supply to the microcirculation with resultant inadequate perfusion of all cells and tissues of vital organ

Question 38

What is shock due to?

Answer 38

1) Decreased blood volume
2) Decreased cardiac output
3) Redistribution of blood

Question 39

What are types of shock?

Answer 39

1. Hemorrhagic/hypovolemic
2. Cardiogenic
3. Septic
4. Anaphylactic/Neurogenic

Question 40

Define Hypovolemic shock:

Answer 40

Due to loss of fluid from vascular compartment (decreased bloodvolume) - as a result of:

a. Loss of blood: Hemorrhage (external) or massive internal hemorrhage
b. Decrease plasma volume: e.g. burns
c. Fluid loss: e.g. diarrhea, excessive urine formation, sweating or vomiting

Question 41

Define cardiogenic shock:

Answer 41

a) Inability of the heart to pump blood
- Myocardial infarction
- Pericardial tamponade (fluid accumulates in the pericardium around the heart)

b) Extensive impairment of cardiac output
- pulmonary embolism

Question 42

What do Hypovolemic and cardiogenic shock result in?

Answer 42

decreased perfusion

Question 43

Define septic shock:

Answer 43

a. Bacteremia
- triggered by microbial infections and is associated with severe systemic inflammatory response syndrome (SIRS)
- The pathogenic mechanism is a massive outpouring of inflammatory mediators from innate and adaptive immune cells that produce arterial vasodilation, vascular leakage, and venous blood pooling
- These cardiovascular abnormalities result in tissue hypoperfusion, cellular hypoxia, and metabolic derangements that lead to organ dysfunction and, if severe and persistent, organ failure and death.

Question 44

Define Anaphylactic, Neurogenic shock

Answer 44

a. Anaphylaxis : Allergic condition; results from systemic vasodilation and increased vascular permeability that is triggered by an immunoglobulin E–mediated hypersensitivity reaction
b. Neurogenic: anaesthesia, injury of spinal cord

Question 45

What is associated with anaphalaic, neurogenic, and septic shock?

Answer 45

Peripheral vasodilation - associated with anaphylaxis, neurogenic and septic shock (due to release of factors (cytokines, bacterial endotoxins, etc.) that cause dilation and increased permeability of the vessels).

Question 46

What are the effects of shock?

Answer 46

The result of decreased tissue perfusion is hypoxic or anoxic cell injury which may lead to further decline in cardiac output (for example as a result of renal failure, heart failure, further endothelial cell damage).