CVPR Week 4: Microvascular control Flashcards
Objectives
What mechanisms regulate organ blood flow?
local control mechanisms
Locall control mechanisms of organ blood flow
- Autoregulation
- Hyperemia
Autoregulation of blood flow definition
to keep it constant
Hyperemia blood flow definition
increasing blood flow
Example of autoregulation
- when exercising the total blood flow increases and the % blood flow to the brain is reduced; however, the brain is still receiving the same amount of blood as it was at rest
- this is an example of autoregulation
Example of hyperemia`
During exercise the blood to the skeletal muscle is increased dramatically from at rest which is an example of hyperemia
Explain the autoregulatory mechanism of blood flow
With increasing pressure how can blood flow remain constant?
by constricting or dilating vessels as specific
changes in resistance have the greatest impact on vascular resistance
How does the autoregulatory mechanism regulate flow?
- an increase in perfusion pressure to the organ will cause an initial increase in blood flow and a stretch of the arterial smooth muscle cell wall
- stretch stimulates smooth muscle cells in that artery
- causes constriction
- causes increased resistance
- and reduces flow
- so this is a negative feedback to increased flow
Myogenic mechanism
- The method of autoregulation
- AKA Bayliss effect
- receptors on the smooth muscle cells
- Mechanosensitive ion channel (MSC)
- Stretch-activated ion channels (SAC)
- sens the pressure and stretch and allow Ca2+ and Na+ into the cell and causes contraction
Bayless effect AKA
Myogenic mechanism or autoregulatory mechanism
A decrease in transmural pressure
- a reduction in perfusion pressure
- artery dilates
- reduces resistance and increases flow up to a steady-state level
Autoregulation description
- mediated by the myogenic response
- mechanism that maintains blood flow to the organs
How is local vascular resistance and blood flow regulated?
A balance of hemodynamic forces determines local vascular resistance and blood flow
- Shear stress causing relaxation
- Myogenic pressure causing contraction
Explain active hyperemia
- Active hyperemia matches blood flow to the metabolic requirements = as metabolism goes up blood flow goes up, as it goes down blood flow goes down
- is associated with capillary recruitment and allow other capillary bed to open and precapillary sphincters will close to other capillary beds
Congestion and hyperemia
- congestion is an increase in blood flow but it is due to an obstruction in outflow which doesn’t have new nutrients
- Hyperemia supplies tissues with new nutrients
What is hyperemia?
increase in blood flow due to greater demand during exercise, heat, digestion, inflammation or in response to ischemia
Explain reactive hyperemia
a transient increase in blood flow due to ischemia
not that the tissue is requiring more nutrients it just is not getting enough nutrients
The magnitude of reactive hyperemia correlates with?
The duration of the occlusion is highly correlative to the magnitude and duration of the reactive hyperemic response is
“A repayment of nutrients to that tissue”
Post-occlusion reactive hyperemia response (PORH)
is used as a measure of endothelial function
panel B is a good hyperemic response
Panel C is a bad hyperemic response and would indicate endothelial dysfunction
There are some normal hyperemic responses in the body
Give an example
The endocardial arteries during systole has very low flow during systole so during diastole there is a hugh hyperemic response
This is why the are at a high risk for ischemia if there is endothelial dysfunction then the hyperemic response may be reduced leading to the ischemia
The contribution of local blood flow mechanisms
4 listed
Metabolic dilation AKA active Hyperemic response
Skin local blood flow control mechanisms
Sympathetic nervous system and temperature
Coronary local blood flow control mechanisms
- ↓ O2 causes dilation
- adenosine is an important dilator to increase blood flow
Pulmonary local blood flow control mechanisms
↓O2 causes vasoconstriction
Cerebral local blood flow control mechanisms
- Myoogenic
- CO2
Skeletal local blood flow control mechanisms
- Sympathetic nervous system
- Metabolic
Renal local blood flow control mechanisms
- Myogenic
- Tubuloglomerular
How is the cerebral circulation regulated
almost exclusively by local mechanisms
- Myogenic autoregulation - constant blood flow over a wide range of pressures
- metabolic regulations
- ↑CO2 or ↓O2 causes vasodilation and increase blood flow
- endothelial factors such as endothelin
- Sympathetic activity (very little under normal circumstances)
Cerebral blood flow control mechanisms
5 listed
- Myogenic autoregulation - constant blood flow over a wide range of pressures
- metabolic regulations
- ↑CO2 or ↓O2 causes vasodilation and increase blood flow
- endothelial factors such as endothelin
- Sympathetic activity (very little under normal circumstances)
Sympathetic control of cerebral blood flow
level of sympathetic activity modulates blood flow but doesn’t actually increase blood flow
Myogenic autoregulation of cerebral blood flow
Metabolic regulation of cerebral blood flow
What organs extracts the most O2 from the % available?
The heart extracts a lot of the available O2
How does the heart get more nutrients
cannot really extract more O2 as the heart already pulls out a lot of blood
so
hypoxia causes dilation but also produces adenosine
adenosine binds to A1 and A2 causing various effects
Adenosine binding to A1 receptors effects
Adenosine binding to A2 receptors effects and location
Vascular smooth muscle
Know adenosine pathways
Hypoxia in the pulmonary circulation
Pulmonary blood flow decreases through vasoconstriction in response to hypoxia
the reason is so that blood will go to better ventilated areas of the lung
What is more powerful local control or sympathetic control of blood flow?
Local control mechanisms override sympathetic vascular control
Exercise effect on blood flow
- Increased sympathetic outflow and decrease in parasympathetic so = ↑ CO and ↑ HR and ↓ flow to GI and Renal due to constriction to the renal and GI systems and the veins
- however local control mechanisms override sympathetic vascular control to organs that need increased blood flow
- increase in metabolites from the tissue so leads to dilation of skeletal muscle beds
- since the skeletal muscle bed is so big and a lot of the flow volume is going to the skeletal muscle
- ↓TPR is decreased during exercise even though the CO is massively increased
Mechanisms of capillary fluid exchange
- pinocytosis
- diffusion
- filtration
Pinocytosis description
exchangeable proteins are moved across by vesicular transport
Diffusion description
small water-soluble substances pass through the pores
Filtration description
lipid-soluble substances pass through the endothelial cells
Describe the mechanisms of capillary fluid exchange
3 listed
Movement of lipid-soluble and small water-soluble substances by diffusion is governed by?
Fick’s Law
Describe Fick’s Law
Rate of diffusion = k x A x (P2 - P1)
D
Where
k = the diffusion constant
A = the area for gas exchange
P2 - P1 = the difference in partial pressure of a gas or concentration of a substance on either side of the membrane
D = distance (the thickness of the barrier to diffusion
this equation determines the rate of diffusion for a given substance based on area available for diffusion, the concentrations or partial pressures of the substance in question and the thickness of the membrane to diffuse across
What does Fick’s law dictate in regards to capillary exchange?
movement of lipid-soluble substances in capillary fluid exchange
Describe the mechanism of pinocytosis
utilize pinocytotic vesicles called (Caveolae)
What are caveolae?
pinocytotic vesicles used to transport across capillary walls
The mechanism of bulk fluid exchange in capillary fluid exchange
Filtration
The mechanism of filtration follows what principle?
Starling hypothesis
Describe Starling’s Hypothesis
Fluid movement (Jv) = Kf [(PC - Pi) - σ(πc - πi)]
where JV = fluid movement
Kf = The filtration coefficient (describes the leakiness of the capillaries and perfusion area)
Pc - Pi = capillary fluid pressure - interstitial fluid pressure
σ = Reflection coefficient (describes the permeability of the capillaries to proteins)
- Proteins move freely when σ = 0
- Impermeable to proteins when σ = 1
πc - πi = capillary plasma colloid osmotic pressure - Interstitial fluid colloid osmotic pressure
What is hydrostatic pressure?
Blood pressure
What is oncotic pressure?
the osmotic pressure due to solute concentrations
Hydrostatic pressure is highest at?
the arteriolar end and lowest at the venular end of the capillary
Oncotic pressure is greatest where?
- pulls the water into the interstitium because solute concentrations are much greater within the blood on the arteriolar side so you get fluid going out to the tissues
- pulls the water into the capillaries because solute concentrations are much greater within the blood on the venular side so you get reabsorption back into the capillary bed
Filtration values interpretations
(Pc - Pi) > (πc - πi) so would be a positive result then have Net Filtration
(Pc - Pi) = (πc - πi) so would = 0 then have No Net Movement
(Pc - Pi) < (πc - πi) so would be a negative result then have Net Reabsorption
How is capillary hydrostatic pressure regulated?
Identify
Arteriole capillary hydrostatic pressure regulation
- Arteriole vasoconstriction decreases capillary hydrostatic pressure then Reduced overall filtration and more reabsorption
- Arteriole dilation increases capillary hydrostatic pressure to increase and get Increased overall filtration and reduce reabsorption
Venule capillary hydrostatic pressure regulation
- Constriction of venules increases capillary hydrostatic pressure and Increases overall filtration and reduces reabsorption
- Dilation of venules decreases capillary hydrostatic pressure and Decreases overall filtration and increases reabsorption
A decrease in blood volume effect on capillary perfusion
a decrease in blood volume also causes venous pressure to fall and result in reduced overall filtration and increased reabsorption
How does oncotic pressure alter filtration?
- In renal or liver failure or malnutrition, filtration is increased and reabsorption is decreased
- WIth dehydration overall filtration is decreased and reabsorption is increased
How quickly do oncotic pressures change?
Quite slowly and usually doesn’t change except in disease states
How quickly do hydrostatic pressures change?
very quickly
How would liver failure affect capillary filtration?
Albumin may not be synthesized appropriately decreasing the blood’s overall oncotic pressure and therefore increased filtration and decreased reabsorption
How would renal failure affect capillary filtration?
In renal failure, you usually have proteinuria so you would pee out proteins so this would decrease the amount of protein in the blood and decrease capillary oncotic pressure
The would increase filtration and decrease reabsorption
How would malnutrition affect capillary filtration?
reduced nutrient uptake from diet can cause reduced blood proteins thereby reducing capillary oncotic pressure
so you would get more filtration and less reabsorption
How would dehydration affect capillary filtration?
dehydration would result in increased blood proteins increasing the capillary oncotic pressure and thereby
decreasing filtration and increasing reabsorption to suck water out of the tissues
Amount of filtration by capillary beds
3L / day
Amount of filtration by kidneys
180 L / day
Describe renal filtration
The kidneys have 2 capillary beds
- blood enters and leaves a glomerular capillary at very high pressures
- Massive quantities of fluid filter into the renal tubule as a result
All the filtration happens in the glomerular capillary bed
The reabsorption occurs in the peritubular capillary bed
Glomerular capillaries pressure 65 mmHg
Identify
Describe the pulmonary capillary bed
15 mmHg because this pressure is so much lower we get all fluid reabsorption in the lung because the hydrostatic pressure in the lung is so much lower than the oncotic pressure we get nothing but reabsorption
Important roles and features of lymphatic capillaries
- Returns 3 L of interstitial fluid and 120 g of protein per day (70kg man)
- Filters lymph (removal of bacteria)
- Maintain circulating levels of immunoglobulins and lymphocytes
Identify
What cells and structure of lymphatics
- lymphatics are endothelial cells
- anchored to tissue
- these endothelial cells overlap each other and create a kind of microvalve
- When interstitial fluid pressure is higher than in the lymphatic fluid pressure these microvalves open and fluid comes in
- when lymphatic pressure gets higher than interstitial pressure these valves close
- when these valves close the secondary valves open and propel the fluid to the lymph nodes and then back into the circulation
Specialized lymphatics
3 listed
- The brain does not have a true lymphatic system because the capillaries in the brain are very tight BBB?
- The liver is very leaky because of the sinusoidal capillaries so the liver lymph has a very high protein concentration and contributes to more than half of the thoracic duct lymph
- Intestine lymph is called Chyle which has a milky white appearance due to the absorption and transport of fat from the small intestine
Chyle is?
intestinal capillary lymph
What causes tissue edema
4 listed
when the capacity of lymphatic is exceeded
- excessive increased hydrostatic pressure (huge arteriole dilation of venous constriction, or a high volume expansion of blood or in heart failure)
- Increased permeability of the vasculature (immune reactions or burns)
- decreased oncotic pressure (malnutrition, liver disease, nephrotic syndrome
- or impaired lymphatic drainage (blocker or impaired and can no longer take up excess fluid)
Heart failure and edema
Right vs left heart failure
Right = congestion and edema occurs in the peripheral tissues
Left = edema occurs in pulmonary and gets pulmonary congestion and edema
Liver and renal failure edema
Objectives
Question 1
Question 2
Question 3
Question 4
Question 5
Question 6
