Microcirculation Flashcards
Describe capillary walls and their permeability.
Capillary walls are one cell thick of endothelium about 42mm thick .
Small and lipophilic substances can pass thru cells . The walls have small gaps called clefts that let other small substances pass through . Any other substance that must diffuse into / out of capillary use vesicles called Caveolae .Different capillaries have different permeabilities based on needs / brain , liver, GI , kidney
Microcirculation
Over 10 billion capillaries with surface area of ~500-700 m2
Transport of nutrients to the tissues
Removal of cell waste
Very thin walls
Controlled by arterioles in each tissue along with precapillary sphincters
Local control
Capillary Walls
One cell thick endothelium
Basement membrane
~0.5 μm total thickness
Contains pores
Intercellular cleft
Caveolae
Brain
Tight junctions – continuous capillaries
Liver
Large clefts - sinusoids
GI tract
Clefts smaller than liver, but still large
Kidney glomeruli
Small oval windows – fenestrated capillaries
Vasomotion
Intermittent flow of blood through capillaries due to regulation via precapillary sphincters and metarterioles or small arterioles
Due to O2 levels of tissue
Bulk Flow in Systemic Capillaries
Transcapillary movement is by bulk flow diffusion
Diffusion is the main method of exchange between plasma and interstitial fluid (fluid in interstitium, found between cells; gel consistency)
Lipid soluble substances pass through cell membrane
Lipid insoluble pass through intercellular clefts
Enhanced by concentration differences
Hydrostatic Pressure
pressure fluid puts on walls
Colloid Osmotic Pressure
pressure solutes put on water, drawing water toward solutes
Capillary Hydrostatic Pressure (Pc)
Tends to push fluid out of capillaries
Interstitial Fluid Hydrostatic Pressure (Pif)
Would tend to pull fluid into capillaries, BUT pulls fluid out of capillaries due to lymphatic drainage
Capillary/Plasma Osmotic Pressure (πp)
Tends to pull water into capillaries by osmosis
Due to presence of proteins (albumin/globulins) in plasma
Interstitial Fluid Osmotic Pressure (πif)
Tends to pull water out of capillaries by osmosis
Due to proteins in interstitium (very low)
Net Filtration Pressure
NFP = outward pressures – inward pressures
NFP = (Pc + πif) – (πp + Pif)
Bulk Flow in Systemic Capillaries
90% of filtered fluid is reabsorbed at venous end
10% is collected by lymphatic system
Lymphatic System
Returns fluid and proteins to the blood
(2-3L/day)
Fluid in lymphatic vessels is called lymph
Prevents edema
Absorbs lipids from GI tract
Role in immune system
lymph flow
aided by smooth muscle and the skeletal muscle pump.
Describe the lymphatic vessel system & its role in preventing fluid accumulation in the interstitial space.
90% of filtered fluid is reabsorbed at the venous end of the capillary .
The remaining 10% is collected by lymphatic capillaries as lymph .
Lymph collecting into the thoracic cavity where , after it has been filtered by lymph nodes , empties back into the veins to contribute to blood volume . lymph flow is aided by smooth muscle and the skeletal muscle pump.
Local Control of Blood Flow
Each tissue controls its own blood flow
Based on tissue needs
Delivery of O2
Delivery of other nutrients: glucose, amino acids, fatty acids
Removal of CO2 and H+
Maintenance of ion concentrations
Transport of hormones and other substances
Flow proportional to metabolic needs
Mechanisms of Blood Flow Control
Acute Control (seconds)
Vasodilation/vasoconstriction
Arterioles, metarterioles, precapillary sphincters
Long-term Control (days, weeks, months)
Increase/decrease in size/number of blood vessels
Acute Control of Local Blood Flow
Increases in metabolism increase flow
Decreases in O2 increase flow
Two theories
Vasodilator theory
O2 demand theory
Vasodilator Theory
Metabolism produces vasodilator substances
Adenosine
Adenosine phosphate compounds
Histamine
CO2
K+
H+
Metabolism produces vasodilator substances
Substances reduce resistance
Flow increases
O2 Demand Theory
O2 decrease in tissues leads to relaxation of smooth muscle
Because O2 is needed for contraction
Relaxation reduces resistance
Flow increases
Reactive Hyperemia
Increase in flow in response to blocked flow
Active Hyperemia
Increase in flow in response to increased metabolism
Explain the factors that control local blood flow
Each tissue controls its own blood flow , directly proportional to metabolic needs . During high metabolic activity of a certain
tissue
ex. Skeletal muscle, GI trait) , flow will increase in that area and decrease in lower energy areas.
2 theories on how this is accomplished
1. Vasodilator theory :
high metabolism produces Vasodilating substances (CO2 , H+) that reduce resistance and increase flow
2. O2 demand theory :
low O2 delivery or high metabolism causes less contraction ,
which reduces resistance and increases flow
Reactive hyperemia : increase in flow after removal of blocked flow
Active hyperemia : increase flow in response to decrease in metabolism
List several substances involved in local and circulating metabolic control of vascular tone and describe how they affect vascular tone.
Vascular tone can be controlled humorally through vasodilators like Bradykinin , histamine, ANP, Serotonin and prostaglandins and
vasoconstrictors like NE , Epi , angiotensin II , and ADH.
It can also be controlled by Vasodilating ions like K+ , Mg”
, H+ and Vasoconstricting ions like Ca++.
Two Theories of Autoregulation
Metabolic theory
Myogenic theory
Myogenic Theory of Autoregulation
Sudden stretch of small vessels leads to contraction
Theory: Stretch of smooth muscles opens mechanically-gated Ca++ channels
Increase in Ca++ in vascular smooth muscle leads to increased contraction
Law of LaPlace
Tension =P ✗ r
Increase pressure - increase tension and decrease radius
Decrease Pressure- decrease tension and increase radius
Describe the myogenic response of blood vessels.
The myogenic theory of response is that in a sudden stretch in small vessels , a contraction of the vessel will occur. This is due to the opening of Mechanically Ca++ Channels in vascular smooth muscle. This mechanism is the default, which can be overridden .
The law of Laplace = Tension =P ✗ r ← allows for constant tension
Explain long-term control of blood flow.
Longterm control is more effective than short term and is due to changes in vascularization. Angiogenesis requires vascular growth factors , which are proteins. These can also be inhibited.
Acute Flow in Specialized Tissues
(Kidneys)
Tubuloglomerular Feedback (in Urinary)
Brain
Also regulated by CO2/H+
Skin
Tied to body temperature regulation
Vasodilators
NO
Released from endothelial cells in response to shear stress (important in larger vessels)
Half life of ~6 sec
Activates guanylate cyclase, which converts GTP to cGMP, which activates PKG, causing relaxation
Vasoconstrictors
Endothelin
Released in response to vessel injury
Prevents blood loss
Autoregulation of Blood Flow
Long term regulation is more effective than short term
Long term changes are due to changes in vascularization
Angiogenesis – formation of new vessels
In response to O2 demand (maximal, not average)
Requires vascular growth factors
VEGF – vascular endothelial growth factor
FGF – fibroblast grown factor
PDGF – platelet-derived growth factor
Angiogenin
Inhibition of vascularization
Angiostatin
Endostatin
Long term regulation
is more effective than short term
Long term changes
are due to changes in vascularization
Angiogenesis
formation of new vessels
In response to O2 demand (maximal, not average)
Requires vascular growth factors
VEGF – vascular endothelial growth factor
FGF – fibroblast grown factor
PDGF – platelet-derived growth factor
Angiogenin
Inhibition of vascularization
Angiostatin
Endostatin
Humoral Control of Circulation (Vasolidators)
Bradykinin
Inflammation
Histamine
Tissue damage/inflammation
Atrial naturetic peptide
High blood volume
Serotonin
Prostaglandins
Vasolidators (Bradykinin)
Inflamation
Vasolidators (Histamine)
Tissue damage/inflammation
Vasolidators (Atrial naturetic peptide)
High blood volume
Humoral Control of Circulation (Vasoconstrictors)
NE (and Epi)
Sympathetic stimulation
Angiotensin II
To increase TPR
ADH
To increase BP
Vasoconstrictors (NE and Epi)
Sympathetic stimulation
Vasoconstrictors (Angiotensin II)
To increase TPR
Vasoconstrictors (ADH)
To increase BP
Control by Ions & Other Factors (Vasodilators)
K+
Mg++
H+
Acetate & citrate (mild)
CO2 (esp. in brain)
Control by Ions & Other Factors (Vasoconstrictors
)
Ca++
