Microcirculation

Microcirculation


Fluid movement (Jv) = Κf [(Pc-Pi)-σ(πc-πi)] 

this applies to GFR in kidneys

Pc

Increased Pc 

• dilation of arterioles
• constriction of veins

Decreased Pc

• constriction of arterioles
• constriction of veins

σ

Reflection coefficient  (0 to 1)  0 = leaky and oncotic pressure doesn't have an effect (multiplied by zero)

*can also be increased under pathophysiological conditions (burns and inflammation)*

should  be "decreased"

Kf  

= hydraulic conductivity (permeability to water)

*can also be increased under pathophysiological conditions (burns and inflammation)*


Edema

• cardiogenic
• increased Pc 
• noncardiogenic
• decreased capillary oncotic pressure
• obstructed lymphatics

Ascites (malnutrition - low protein edema)

Local Control of Blood Flow

Active Hyperemia  -  metabolites dilate arterioles

Reactive hyperemia  -  after reduced flow, flow increases (low O2, metabolites)

Hypoxia vasodilates in peripheral circulation but vasoconstricts in pulmonary circulation

• alveolar hypoxia triggers inhibition of voltage gated K+ channels in arterioles leading to depolarization then activation of voltage gated Ca++ channels = vasoconstriction.

Hemodynamic Forces on Vasculature

muscle types; endothelin; pulse pressure

no troponin in smooth muscle.  Calcium binds to calmodulin, activates MLCK, phosphorylation triggers actin-myosin crossbridge = contraction.

Beta agonists lead to increased cAMP which inhibits MLCK = relaxation.  Same receptor but opposite effects on vascular and cardiac muscle.


Viagra targets  PDE5  Mainly in groin and lungs.

Good reference for this stuff


Part 2:  Endothelium

ET-1  most potent vasoconstrictor of any

compliance = delta Vol/delta P

pulse pressure = delta P    stroke volume = delta V

pulse pressure = stroke volume/compliance

decreased compliance (aterosclerosis) = increased pulse pressure

Electrolytes and ECG; Pressure Volume Loops; Reflex control of the heart

electrolytes and ECG

K+   Nernst equation shows that hypoK = hyperpolarization and hyperK = hypopolarization
Major effect, hower, is due to changes in ion currents

Mg++
hypoMg++ similar to hypoK+  for ECG changes

Ca++
hyperCa++  

• shortens QT
• ST segment abolished

Ischemia

• depolarization of resting membranes
• inactivates fast Na channels = slows phase 0 = slows conduction cell to cell
• local acidosis
• K leakage from cell
• arrythmias due to dispersion of refractoriness in different parts of heart
• ST segment elevation in infarct zones and depression in reciprocal leads

Arrhythmia mechanisms associated with ischemia 

• A-V Block, Bundle Branch & Fascicular Blocks 
•  Bradyarrhythmias 
• Enhanced Automaticity 
• PVCs 
• Triggered Activity 
• Polymorphic VT 
• Reentry 
• Monomorphic VT 
• Ventricular Fibrillation

Hypothermia

• Osborn or J wave: A hump-like elevation of the J-point at the onset of ST segment. 
• Caused by dispersion of endocardial to epicardial phase 1 repolarization. 
• Shivering (muscle) artifact. 
• QT prolongation.

Pressure - Volume loops

Positive inotropic agents (digoxin, dopamine, dobutamine, eicosanoids, epinephrine, inamrinone, isoprenaline, milrinone, norepinephrine, phosphodiesterase inhibitors, theophylline)


Negative inotropic agents (beta-blockers, calcium channel blockers, disopyramide, flecainide, procainamide, quinidine)

Reflex control of the heart

read more

Of these two sites for arterial baroreceptors, the carotid sinus is quantitatively the most important for regulating arterial pressure. The carotid sinus receptors respond to pressures ranging from 60-180 mmHg 

important to know that carotid baroreceptor activity is proportional to blood pressure.

switch from sympathetic stimulation to sympathetic inhibition due to GABA release by CVLM

summary figure  P = QR

Efferent Limb: Autonomic Responses

MABP = CO x TPR          

memory tool: alphabet rule  ABC 

PQR   or P = QR

Cardiac Pathology

Cardiac Pathology


dilation = loss of overlap of actin and myosin = weaker contraction
            = distorted gap junctions

Heart Failure = defined as decreased cardiac output

• pressure overload -  concentric hypertrophy = sarcomeres added in parallel
• volume overload - dilated ventricle = sarcomeres added in series - eccentric hypertrophy

Cardiomegaly

• bigger is not better
• increased size does not come with increased capillaries
• Exception - physiological hypertrophy

Heart Failure

dead myocytes are replaced by scar tissue

Chronic ischemic heart disease

at autopsy:

• Enlarged, heavy hearts 
• Left ventricular hypertrophy and dilation 
• Discrete scars = healed infarcts 
• Increased fibrosis 
• Subendocardial vacuolization

Acute MI

at autopsy:

• normal

Hypertensive Heart Disease

Cardiomyopathies - mechanical & electrical (gap junction) problems

Dilated = systolic dysfunction (decreased overlap of actin-myosin); 

• Genetic - 20-50%
• Infections – VIRAL 
• Toxins - ALCOHOL 
• Metabolic – thyroid disorders 
• Neuromuscular disease – muscular dystrophy 
• Storage disorders – glycogen storage disease 
• Infiltrates – leukemia 
• Immunological; e.g, lupus
• Peripartum
• Restrictive 

Hypertrophic

• myocyte disarray
• outflow obstruction due to hypertrophy
• genetic - mutations in genes that encode sarcomeres

Restrictive

• decrease in ventricle compliance (deltaV/deltaP
• Causes 
• Radiation fibrosis 
• Amyloidosis -amyloid deposited between myofibrils
• Sarcoidosis - granulomas
• Metastatic tumors - multiple transfusions - iron overload
• Inborn errors of metabolism 

Myocarditis - inflammation of myocardium

Viral myocarditis 

• Causes MOST cases in the US 
• Coxsackie viruses A and B most common 
• Also see other enteroviruses, CMV, HIV, etc 
• Presentation ranges from sudden death to heart failure 
• Other 
• Rickettsiae, bacteria (diphtheria, Lyme disease), fungal 
  

  (candidal), protozoal (Chagas disease and 

  toxoplasmosis) 
• Hypersensitivity myocarditis - eosinophils present
• Giant-cell myocarditis - giant cells = collection of macrophages

Miscellaneous Myocardial Disease

• Cardiotoxic drugs 
• Catecholamines 
• Amyloid 
• Iron overload 
• Hyper and hypothyroidism

Cardiac Tumors

• myxoma - most common - usually in left atrium
• etc.

Pericardial Disease

• fluid volume in pericardium normally < 50 ml
• pericarditis = inflammation of pericardium = increased fluid (effusion)
• serous = non infectious inflammation
• fibrinous = most common; acute MI, radiation, autoimmune, trauma
• purulent = infections