SM 118a - Microcirculation Flashcards
Which mechanisms govern water soluble solvent transfer in and out of capillaries?
-
Small molecules
-
Diffusion through endothelial junctions
- Must pass through a gauntlet of fiber matrix
- Glycocalyx
- Protein constituents
- Must pass through a gauntlet of fiber matrix
-
Diffusion through endothelial junctions
-
Larger molecules (plasma proteins)
-
Vesicular transport via transcytosis (active transport)
- This mechanism dominates
- Diffusion through fenestrations in fenestrated capillaries or gaps in discontinuous capillaries
-
Vesicular transport via transcytosis (active transport)
What is the Starling Equation?
What does it predict?
The Starling Equation predicts the net absorption into or filtration out of a capillary
- Note:
- Fluid out of the capillary is (+)
- Fluid into the capillary is (-)
- P = Hydrostatic pressure (pushes fluid out due to volume)
- Pi = Oncotic pressure (sucks water toward it due to osmosis)
What is the reversal point of a capillary?
The point in the capillary where net filtration ends and net absorption begins.
- Predicted by the Starling Equation
- Filtration is early to deliver nutrients along their concentration gradient
- Absorption is later to remove waste products, also along their concentration gradient
Describe the sequence of lymphatic flow from capillaries
Increased interstitial pressure initiates movement into lymphatics
- Expansion phase
- P(interstitium) is greater than P(lymph), forcing fluid into the lymphatics
- 1-way microvalves open
- Compression phase
- Fluid flow into the lymphatics raises P(lymph) above P(interstitium)
- The 1-way microvalves close (this prevents flow back into the interstitium)
- Secondary lymph valves open, allowing the lymph to enter the thoracic duct
What prevents flow from the lymphatics to the interstitial spaces?
1-way valves that only allow for flow from the interstitium to the lymph
List the two systemic and three local mechanisms for control of blood flow
Systemic
- Neural
- Hormonal
Local
- Myogenic
- Metabolic
- Endothelial
Describe neural control of blood flow
Systemic, controlled by the sympathetic nervous system
- Vasoconstrictor nerves secrete norepinephrine
- Activates alpha-1 adrenergic receptors on smooth muscle
- Vasoconstriction in nonessential muscles
- Activates alpha-1 adrenergic receptors on smooth muscle
- Adrenal medulla secretes epinephrine
- Activates beta-2 adrenergic receptors in skeletal muscle/smooth muscle endothelium that carries blood to exerscising muscles
- Vasodilation in excercising muscle
- Activates alpha-1 adrenergic receptors on smooth muscle that is not needed for exercise
- Vasoconstriction in nonessential muscles
- Activates beta-2 adrenergic receptors in skeletal muscle/smooth muscle endothelium that carries blood to exerscising muscles
In neural control of blood flow, what determines whether there is net vasodilation or net vasoconstriction in a given tissue?
- Relative alpha-1 and beta-2 receptors in a given tissue
- Mixture of epinephrine and norepinephrine released
Describe hormonal control of blood flow in response to trauma
Systemic
- Trauma
- -> Histamine Release
- -> Arteriole dilation and venule constriction
- -> Increased pressure in the capillaries
- -> Increased filtration out of the capillaries, due to increased hydrostatic pressure in the capillary
- -> Local edema
Describe myogenic control of blood flow
Local
- Increased local blood flow
- -> Stretch in vascular smooth muscle
- -> Response mediated by stretch receptors
- Reflex constriction
- Increased local resistance
- Local blood flow returns to normal
Describe metabolic control of blood flow
- Metabolically active tissue generate vasodilator metabolites
- Lactate
- Adenosine (breakdown of ATP)
- K+; if cells lyse, K+ in the blood goes up
- H+ (more acidic)
- CO2
- Also sense interstitial concentrations of…
- Decreased pO2
- Increased pCO2
- Decreased interstitial pH
- All of the above trigger increased blood flow
- Wash away waste products (and deliver more oxygen)
- Re-establish equilibrium
Describe endothelial control of blood flow
- Endothelial cells make certain substances
- Vasodilators
- Nitric Oxide
- Generated by endothelial NO synthase (eNOS)
- Converts arginine to NO
- Prostaglandins
- Nitric Oxide
- Vasoconstrictors
- Endothelin (ET) = vasoconstrictor
- Binds ET receptors on vascular smooth muscle
- Increases cytosolic Ca2+
- Released by endothelial cells in response to hypoxia and other stimuli
- Binds ET receptors on vascular smooth muscle
- Thromboxanes
- Endothelin (ET) = vasoconstrictor
What is the effect of prostaglandin on local blood flow?
Protsaglandin is a vasodilator: increases local blood flow
What is the effect of thromboxane on local blood flow?
Thromboxane is a vasoconstrictor: decreases local blood flow
Describe autoregulation of blood flow
- MAP can increase or decrease to keep blood flow to an area constant
- Works in a broad range
This graph shows which pattern of blood flow regulation?
Autoregulation
Describe active hyperemia
- Organ blood flow increases in response to increased metabolic rate
- Blood flow increases to match the metabolic demands of a tissue
- Local metabolic mechanisms are responsible
Which mechanism of blood flow regulation is responsible for active hyperemia?
Metabolic (local)
This graph shows which pattern of blood flow regulation?
Active Hyperemia
This graph shows which pattern of blood flow regulation?
Reactive Hyperemia
Describe reactive hyperemia
- Organ blood flow responds to a period of arrested blood flow
- Blood flow increases after insufficient blood flow
- Flushes away toxins
- Local metabolic and myogenic mechanisms are responsible
Which mechanisms of blood flow regulation are responsible for reactive hyperemia?
- Metabolic (Local)
- Myogenic (Local)
Which mechanism of blood flow regulation relies on the baroreceptor reflex?
Myogenic
Which pattern of blood flow regulation is likely to dominate during exercise?
Active hyperemia, regulated by metabolic mechanisms
Which pattern of blood flow regulation is likely to dominate after anginal pain has subsided?
Reactive hyperemia, regulated by metabolic and myogenic mechanisms
Which mechanism of blood flow regulation dominates in the coronary arteries?
- Metabolic (local)
- Sensitive to hypoxia and adenosine
Which metabolic conditions is the coronary circulation most sensitive to?
- Hypoxia
- Adenosine (breakdown of ATP)
Which mechanism of blood flow regulation dominates in the cerebral circulation?
- Metabolic (local)
- Sensitive to ischemia
Which metabolic condition is the cerebral circulation most sensitive to?
Ischemia
What physiologic response is activated in response to increased intracranial pressure?
- Cushing reflex
- Increased intracranial pressure -> decreased blood flow
- Cushing reflex increases systemic pressure above intracranial pressure to maintain blood flow to the brain
Which mechanism of blood flow regulation dominates in the pulmonary circulation?
- Metabolic (local)
- Sensitive to changes in pO2
Which metabolic condition is the pulmonary circulation most sensitive to?
Changes in pO2
In the pulmonary circulation, what is the response to hypoxia?
Why does this make physiologic sense?
- In the pulmonary circulation, hypoxia leads to vasoconstriction
- Paradoxically, this further restricts blood flow and oxygen delivery
- However, this makes sense in the lungs:
- If a tissue is ineffective for gas exchange (ex: filled with mucus or not working), it is a “waste of circulation” to perfuse it
Which mechanism of blood flow regulation dominates in the skeletal muscle?
- Metabolic (local)
- Sympathetic (systemic)
Which metabolic condition is the skeletal muscle circulation most sensitive to?
Increases in…
- Lactate
- Adenosine
- K+
- Epinephrine acting on beta-2 receptors
All cause vasodilation
What system in the body is responsible for determining TPR?
Skeletal Muscle
What percentage of the total body circulation goes to skeletal muscle at rest?
80%
(More during exercise)
What percentage of the total body circulation goes to the coronary arteries at rest?
5%
(More during exercise)
What is the muscle pump that is sometimes referred to as the “2nd heart?”
The skeletal muscle surrounding veins
Contractions in a pumping pattern increase venous return
What are glomus bodies? Where are they found? What do they do?
Glomus bodies are arterio-venous anastomoses in apical skin that are under sympathetic control.
- They function to control heat conservation or dissipation in apical skin
- If there is a decrease in core temperature, norepinephrine secreted by sympathetic neurons acts on alpha-1 receptors in glomus bodies, causing constriction
- Decreased blood flow -> decreased heat loss
- If there is an increase in core temperature, sympathetic tone is withdrawn
- Glomus bodies dilate
- Increased blood flow -> increased heat dissipation
What regulates blood flow in apical skin in response to core temperature changes?
Glomus bodies
- They constrict in response to decreased core temperature, due to sympathetic input
- Heat conservation
- They dilate in response to increased core temperature, due to decreased sympathetic tone
- Heat dissipation
In non-apical skin, how does blood flow change in response to acetylcholine release by neurons?
Blood flow increases due to vasodilation
