Microcirculation Flashcards
3 aspects of microcirculation
1. Capillary exchange of solutes Diffusion 2. Capillary exchange of water Starling forces 3. Lymphatics
what is microcirculation
The “point” of the circulatory system for multi-cellular organisms
Site of exchange: gases, water, nutrients, waste
What is exchanged by simple diffusion?
A. Lipid-Soluble Substances
O₂, CO₂, other non-polar substances
Diffusion across endothelial cells
B. Water-Soluble Substances
Na+, K+, glucose, amino acids, other polar substances
Diffusion across clefts between endothelial cells
Plasma proteins are generally too large to pass
How does tissue metabolism influence concentration gradient? example of oxygen
Depletion of cellular O₂ increases gradient to promote increased rate of diffusion, maximizing A-V O₂ difference by increasing O₂ extraction
Capillary Exchange of Fluid: Bulk Flow
Water exchange depends on Net Starling Forces across the capillary membrane
Net Hydrostatic Pressure:
Difference between capillary & interstitial fluid pressures:
Net Osmotic Pressure
Difference between capillary & interstitial fluid colloid osmotic pressures (proteins)
Factors influencing net filtration pressure (the 4 Starling forces)
1. Capillary BP (Pc ) Hydrostatic pressure (BP): out
2. Plasma-colloid osmotic pressure (πP ) Osmotic pressure (plasma proteins): in
- Interstitial fluid hydrostatic pressure (PIF )
Hydrostatic pressure: in (small)
4. Interstitial fluid-colloid osmotic pressure (πIF ) Osmotic pressure (leaked proteins): out (minimal)
Net driving force and starling equation
NDF = (cappillary P - interstitial P) - sigma (capillary collooid osmotic pressure - interstitial fluid colloid osmotic pressure)
If it’s positive, then filtration is occuring (NDF > 0) (fluid is moving out)
If it’s negative, then reabsorption is occuring
the sigma is not important
BLUF: are the inward pressures greater than the outward pressures? –> reabsorption
What important variable in the starling equation changes most through the course of the circulatory system?
Outward pressure from capillary (blood pressure)
Factors impacting filtration & reabsorption (is edema formation promoted or not?)
Capillary hydrostatic pressure (promotes filtration)
Plasma-colloid osmotic pressure (promotes reabsorption)
interstitial fluid hydrostatic pressure (typically close to 0)
Interstital fluid-colloid osmotic pressure (promotes filtration)
Factors impacting capillary hydrostatic pressure (which promotes filtration)
Increased by:
Arteriolar dilation
Increased venous pressure (causes blood to back up)
Hypertension
Decreased by:
Arteriolar constriction
Hemorrhage/blood loss
Factors impacting plasma-colloid osmotic pressure (which promotes reabsorption)
Increased by:
Dehydration (excessive sweating) –>increased protein
Decreased:
Liver failure, protein malnutrition, nephrotic syndrome, pregnancy
Saline infusion
interstitial fluid hydrostatic pressure changes
Typically close to zero
Clinically relevant changes involve pulmonary circulation, edema
Interstitial fluid-colloid osmotic pressure factors
Increased by:
Chronic Lymphatic Blockage
Burns (increased capillary permeability)
Lymphatic System
Accessory route: Filtered fluid & protein returned to circulation from interstitial spaces
Filtration > Reabsorption
~ 1/10 of fluid enters lymphatics vs. being reabsorbed in capillaries –> 2-4 L/day!
Important in preventing edema
Edema Develops When: Filtered volume > lymphatic capacity
Lymph = interstitial fluid that flows into the lymphatic system
Edema develops when…
filtered volume > lymphatic capacity
Factors that increase lymph flow and increase likelihood of edema formation
- Increased capillary hydrostatic pressure
- Decreased plasma colloid osmotic pressure
- Increased interstitial fluid colloid osmotic pressure
- Increased capillary permeability
Each factor causes the balance of fluid exchange to favor net fluid movement out of the capillary bed and into the interstitium (net filtration), resulting in ↑ interstitial fluid volume, interstitial fluid pressure, & lymph flow. These factors can also promote edema.
Coronary blood supply issues
Cardiac output distribution: ∼5% ( Skeletal m. (~3000/mm2 vs. ~400/mm2)
Resting cardiac m. O2 consumption almost = exercising skeletal m. per mass
Fiber diameter: Cardiac m.
types of coronary arteries
Epicardial Coronary Arteries (LCA/RCA) Main coronary arteries on the surface of the heart
Intramuscular arteries Smaller communicating arteries pass through myocardium
Subendocardial Arteries
Deep to the endocardium
Coronary blood flow during cardiac cycle
Blood flow through coronary arteries depends on:
Perfusion pressure at aortic openings
Extravascular compression due to ventricular contraction (especially left ventricle)
LV Myocardial contraction effectively compresses its own vascular supply
Pressures especially compress subendocardial a.a.
∼80% of LCA blood flow occurs during diastole
RV develops lower pressure during systole
RCA blood flow is not significantly occluded during contraction
Cardiac muscle metabolism
Resting myocardial O2 consumption
> 60% fatty acid oxidation
O2 supply (anaerobic/ischemic conditions): Anaerobic glycolysis results in lactic acid production
Possible cause of angina during ischemia
Myocardial O2 consumption at rest
Rest:
Blood flow: ~ 60 - 80 mL/min of blood per 100 g myocardium
O2 extraction: ~ 70 - 80% of arterial O2 content (∼20 mL/dL)
Very low venous O2 content (∼5 mL/dL)
Key Concepts:
Metabolic signals are key drivers of myocardial O2 delivery
Myocardial blood flow parallels myocardial metabolism
Autoregulation
O2 extraction is near max at rest
Myocardial O2 consumption during exercise
↑ coronary blood flow: Key to meeting large increases in O2 demand during exercise
**Extraction is near maximal at rest
Minimal capability to meet increased metabolic demands by increasing O2 extraction beyond resting levels
Coronary blood flow: Exercise > 250 mL/min per 100 g Flow may increase > 5x Coronary Flow Reserve (using dilation, etc.)
Rate-Pressure Product
Indirect index of myocardial O2 consumption (how hard is the heart working?)
Non-invasive, reasonable correlation with changes in myocardial O2 consumption
RPP = HR x SBP
Based on cardiac work: Rate and Pressure
Myocardial O2 supply and demand
Supply: O2 content affected by coronary blood flow:
- coronary perfusion pressure
- coronary vascular resistance
- external compression
- intrinsic regulation
- local metabolites
- endothelial factors
- neural innervation
Myocardial oxygen demand affected by:
- wall stress
- heart rate
- contractility
Autoregulation of coronary blood flow
Ohm’s Law: Flow determined by pressure gradient and resistance
MAP: little variation, even with exercise
CBF is relatively stable at perfusion pressures of ∼70 - 150+ mm Hg
↓ resistance in order to ↑ flow to exercising myocardium Vasodilation Decreased O2 supply promotes vasodilation of coronary vessels O2 demand > O2 supply: vasodilation Active hyperemia: Adenosine Increased Pco2 NO H+ Prostaglandins
Adenosine and Coronary Blood Flow
↓ Myocardial PO2 → (due to increased metabolic activity or insufficient coronary blood flow) ↑ Adenosine levels
Adenosine acts on vascular smooth muscle cells (VSMC), lowering [Ca2+]i and inducing vasodilation
Inadequate perfusion elevates interstitial adenosine, promotes vasodilation & restores flow to affected region
Autoregularion and Neural Input
Autoregulation & vasodilation prevail during exercise
Parasympathetic Minimal ACh receptor distribution on coronary vessels, Minimal vasodilatory effect
Sympathetic
α1: vasoconstriction with epinephrine & norepinephrine
Expression: epicardial a.a. > endocardial a.a.
β2: vasodilation with epinephrine and norepinephrine
Expression: endocardial a.a. > epicardial a.a.
Coronary Blood Flow: Tachycardia
Tachycardia: ↓ time for maximal perfusion during diastole
Impacts CBF, perfusion of LV is especially compromised
Coronary Blood Flow: Healthy Heart
Coronary vessels autoregulate and adequately dilate
Compensate for shorter diastole
Coronary Blood Flow in Coronary Artery Disease
Stenosis: restriction of blood flow
Exertional Angina
Vasodilator Stimuli: Coronary Steal
Vasodilator drugs or exercise:
When atherosclerotic plaque is present in large epicardial a.a.
Tissue distal to stenotic lesion is especially vulnerable to ischemia because arterioles may be maximally dilated at ‘rest’ in effort to compensate for stenosis
There may be insufficient Coronary Flow Reserve capacity to further dilate in order to meet demand with exercise or in response to a vasodilator drug
If arterioles distal to stenosis are maximally dilated, vasodilation can only affect vessels in non-ischemic vascular beds
Coronary/Vascular Steal: Additional reduction in perfusion pressure downstream of stenosis, further compromising blood flow to ischemic tissue
Ischemic Heart disease examples
Angina pectoris
Myocardial infarction
Angine pectoris
myocardial hypoxia triggers nociceptive fibers; referred pain
Myocardial infarction: severe or prolonged hypoxia damaging myocardium.
Atherosclerosis is primary cause
- CBF restriction: Subendocardium is generally first to be damaged
