1. Hormonal Control of BP and Flow
Angiotensinogen (prohormone produced by liver) 
Angiotensin I
Angiotensin II
very potent vasoconstrictor
Renin (kidney enzyme released by low BP)
ACE (angiotensin-converting enzyme in lungs)

2. Hormonal Control of BP and Flow
Aldosterone ( BP)
promotes Na+ and water retention by kidneys
increases blood volume and pressure
Atrial natriuretic factor ( BP)
generalized vasodilation
ADH ( BP)
Antidiuretic hormone (water retention)
Epinephrine and norepinephrine effects
most blood vessels
binds to -adrenergic receptors, vasoconstriction
skeletal and cardiac muscle blood vessels
binds to -adrenergic receptors, vasodilation

3. Anti-hypertension drugs
ACE inhibitors block the conversion of Angiotensin I to Angiotensin II (coughing?) (less effective in some people)
Diuretics decrease total blood volume (K sparing or not)
Beta-blockers (or alpha blockers) block the beta adrenergic receptors
Angiotensin II receptor blockers – ARBS (esp diabetics)
Calcium channel blocker - Cause vasodilation
Nitroglycerin! for emergencies?

4. Routing of Blood Flow Localized vasoconstriction
pressure downstream drops, pressure upstream rises
enables routing blood to different organs as needed
Arterioles - most control over peripheral resistance
located on proximal side of capillary beds
most numerous
more muscular by diameter

5. Blood Flow in Response to Needs
Arterioles shift blood flow with changing priorities

6. Blood Flow Comparison During exercise
 perfusion of lungs, myocardium and skeletal muscles  perfusion of kidneys and digestive tract

7. Capillary Exchange
Only occurs across capillary walls between blood and surrounding tissues
3 routes across endothelial cells
intercellular clefts
fenestrations
through cytoplasm
Mechanisms involved
diffusion, transcytosis, filtration and reabsorption

8. Capillary Exchange - Diffusion
Most important mechanism
Lipid soluble substances
steroid hormones, O2 and CO2 diffuse easily
Insoluble substances
glucose and electrolytes must pass through channels, fenestrations or intercellular clefts
Large particles - proteins, held back

9. Capillary Exchange - Transcytosis
Pinocytosis - transport vesicles across cell - exocytosis
Important for fatty acids, albumin and some hormones (insulin)

10. Capillary Exchange - Filtration and Reabsorption
Opposing forces
blood (hydrostatic) pressure drives fluid out of capillary
high on arterial end of capillary, low on venous end
colloid osmotic pressure (COP) draws fluid into capillary
results from plasma proteins (albumin)- more in blood
oncotic pressure = net COP (blood COP - tissue COP)
Hydrostatic pressure is defined as a physical force exerted against a surface by a liquid. (BP is an example)

11. Capillary Filtration and Reabsorption
Capillary filtration at arterial end
Capillary reabsorption at venous end
Variations by location (glomeruli vs. alveolus)

12. Three Causes of Edema
 Capillary filtration ( capillary BP or permeability)
poor venous return
congestive heart failure - pulmonary edema
insufficient muscular activity
kidney failure (water retention, hypertension)
histamine makes capillaries more permeable
 Capillary reabsorption
hypoproteinemia (oncotic pressure  blood albumin) cirrhosis, famine, burns, kidney disease
Obstructed lymphatic drainage

13. Consequences of Edema Tissue necrosis Pulmonary edema Cerebral edema
oxygen delivery and waste removal impaired
Pulmonary edema
suffocation
Cerebral edema
headaches, nausea, seizures and coma
Circulatory shock
excess fluid in tissue spaces causes low blood volume and low BP

14. Mechanisms of Venous Return
Pressure gradient
7-13 mm Hg venous pressure towards heart
venules (12-18 mm Hg) to central venous pressure (~5 mm Hg)
Gravity drains blood from head and neck
Skeletal muscle pump in the limbs
Thoracic pump
inhalation - thoracic cavity expands (pressure ) abdominal pressure , forcing blood upward
central venous pressure fluctuates
2mmHg- inhalation, 6mmHg-exhalation
blood flows faster with inhalation
Cardiac suction of expanding atrial space
Breathing!

15. By the time the blood makes it through the capillary bed, blood pressure has dropped to almost zero.
Blood returns to the heart through the veins largely by the action of your muscles in concert with the valves in your veins.

16. Venous Return and Physical Activity
Exercise  venous return in many ways
heart beats faster, harder
vessels of skeletal muscles, lungs and heart dilate  flow
 respiratory rate  action of thoracic pump
 skeletal muscle pump
Venous pooling occurs with inactivity
venous pressure not enough force blood upward
with prolonged standing, cardiac output may be low enough to cause dizziness or syncope
prevented by tensing leg muscles, activate skeletal m. pump
jet pilots wear pressure suits

17. Circulatory Shock
Any state where cardiac output is insufficient to meet metabolic needs
Cardiogenic shock - inadequate pumping of heart (MI)
Hypovolemic shock (a form of low venous return shock)
loss of blood volume: trauma, burns, dehydration
Septic shock
bacterial toxins trigger vasodilation and ↑ capillary permeability
Anaphylactic shock
severe immune reaction to antigen, histamine release, generalized vasodilation, ↑ capillary permeability

18. Responses to Circulatory Shock
Compensated shock – may be manageable
Decompensated shock - bad

19. Compensated shock Homeostatic mechanisms bring about recovery
 BP triggers baroreflex and production of angiotensin II, both stimulate vasoconstriction
If person faints and falls to horizontal position, gravity restores blood flow to brain; quicker if feet are raised

20. Decompensated shock Life threatening positive feedback loops occur
 cardiac output myocardial ischemia and infarction  cardiac output goes down even more
slow circulation  disseminated intravascular coagulation  slow circulation
ischemia and acidosis of brainstem   vasomotor tone, vasodilation   caridac output  ischemia and acidosis of brainstem

21. Special Circulatory Routes- Brain
Total perfusion kept constant
seconds of deprivation causes loss of consciousness
4-5 minutes causes irreversible brain damage
Responds to changes in blood pressure and chemistry
cerebral arteries: dilate as BP , constrict as BP rises
main chemical stimulus: pH
CO2 + H2O  H2 CO3  H+ + (HCO3)-
hypercapnia (CO2 ) in brain, pH , triggers vasodilation
hypocapnia,  pH, vasoconstriction
occurs with hyperventilation, may lead to ischemia, dizziness and sometimes syncope

22. TIA’s and CVA’s TIA’s - transient ischemic attacks
dizziness, loss of vision, weakness, paralysis, headache or aphasia
lasts from a moment to a few hours, often early warning of impending stroke
CVA - cerebral vascular accident (stroke)
Two types
brain infarction caused by ischemia
atherosclerosis, thrombosis, ruptured aneurysm
hemorrhagic stroke
effects range from unnoticeable to fatal
blindness, paralysis, loss of sensation, loss of speech common
recovery depends on CAUSE, surrounding neurons, collateral circulation, gender

23. Special Circulatory Routes - Skeletal Muscle
Highly variable flow – OPPOSITE of brain
At rest
arterioles constrict, total flow about 1L/min
During exercise
arterioles dilate in response to epinephrine and sympathetic nerves
precapillary sphincters dilate due to lactic acid, CO2
blood flow can increase 20 fold
Muscular contraction impedes flow
isometric contraction causes fatigue faster than isotonic

24. Special Circulatory Routes - Lungs
Low pulmonary blood pressure
flow slower, more time for gas exchange
capillary fluid absorption
oncotic pressure overrides hydrostatic pressure
Unique response to hypoxia
pulmonary arteries constrict to redirect flow to better ventilated region

25. Pulmonary Circulation
Pulmonary trunk to pulmonary arteries to lungs
lobar branches for each lobe (3 right, 2 left)
Pulmonary veins return to left atrium
increased O2 and reduced CO2 levels

26. Pulmonary Capillaries Near Alveoli
Basketlike capillary beds surround alveoli
Exchange of gases with air at alveoli

27. Unbalanced Ventricular Output
Both ventricles must eject same amount of blood.
They should have the same stroke volume.

28. Unbalanced Ventricular Output
Both ventricles must eject same amount of blood.
They should have the same stroke volume.

29. That’s it for today