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Physiology

for 1st year medical students

Vascular (1)

A.F.2023
Tel 010 170 71 512

A.F. 2023 1
➢ Blood Flow:
• Flow: volume of fluid that crosses a point per time (e.g. cm3/second).
• Relationship between flow (F), pressure (P), and resistance (R) in blood vessels:
F=∆P÷R
➢ Volume of Blood in the Different Parts of the Circulation
• 84% in the systemic circulation:
▪ 64% in the veins.
▪ 13% in the arteries.
▪ 7% in the arterioles and capillaries.
• 16% in heart and lungs:
▪ 7% in the heart.
▪ 9% in pulmonary vessels.

Venous Circulation
➢ Functions of Veins
1. Blood reservoir (large capacity vessels):
• Significant volumes of blood can be changed with only little changes in pressure:
200 ml of blood rises venous pressure to only one mm Hg.
• specific blood reservoirs: Certain portions have large compliance and contribute
more: cutaneous veins, hepatic and large abdominal veins and the spleen.
2. Transport vessels: offer little resistance to blood flow.
➢ Venous Blood Flow: slower than arterial (25% of aorta) & faster than capillary flow
➢ Venous Pressures:
1. Central Venous Pressure (CVP) “Right Atrial Pressure (RAP)”:
▪ Normally: 0-2 mm Hg.
▪ represents a balance between:
1) Flow of blood from peripheral veins (venous return).
2) ability of heart to pump blood.
▪ Significance:
A. Physiological:
1. main force for ventricular filling.
2. gradient for venous return: Difference between CVP and MSFP
B. clinical:
3. index of blood volume: ↓ volume (hemorrhage) → decrease CVP & Venous return
4. increased in right-sided heart failure.: failing ventricle is unable to pump blood
returning to right atrium: Blood accumulate in right atrium and CVP increase.
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2. Peripheral venous pressure “Pv”:
• In a recumbent person:
- in peripheral small venules: 8-12 mmHg
- in larger veins outside thorax: 5-6 mmHg
- in major veins entering right atrium: 4-5 mmHg above CVP.
• determined by two factors:
1- Venous blood volume
2- Compliance of veins: determined mainly by venous tone = Sympathetic
• affected by:
1. Cardiac output: decreased CO (e.g. ventricular failure) results in blood backing in
venous circulation → Pv rises.
2. Arteriolar dilation: e.g. in skeletal muscles during exercise, leads to increasing blood
flow to veins, Venous volume increases and Pv rises.
3. Total blood volume:
- increased blood volume e.g. in renal failure: ↑ venous volume and Pv rises.
- Decreased blood volume (e.g. hemorrhage): ↓ Pv.

4. Venous tone: venoconstriction (sympathetic) → ↓ venous compliance and Pv ↑.


5. Effect of Gravity on Venous Pressure: In upright position:
▪ Below level of right atrium: pressure increases by 0.77 mm Hg for each cm:
pressure in leg veins increases from 20 mm Hg in recumbent to 80 mmHg
during standing: may cause edema and varicose veins.
▪ Above level of right atrium: pressure decreases by 0.77 mm Hg for each cm:
Head and neck veins are collapsed as pressure is sub-atmospheric.

➢ Venous Return and its Regulation:


• Def.: volume of blood returning to heart per minute.
• N.B.: Under normal conditions, venous return is equal to cardiac output (5 L/min).
• Ohm’s law:

A.F. 2023 3
1- Mean systemic filling pressure (MSFP): (Normally: 6-8 mmHg)
• MSFP: force drives blood back to heart (pressure drives venous return)
• MSFP reflects relationship between:
1) Blood volume.
2) Capacity of circulation, (mainly capacity of veins).
• reflects degree of distension of circulation: The more circulation is distended with
blood the more blood is forced back to heart.
• if cardiac output decreases:
▪ Mean arterial pressure gradually decreases.
▪ RAP gradually rises (due to blood backing).
- If heart stops pumping: cardiac output reaches zero & arterial pressure = RAP.
• Decreased blood volume or increased capacity (decreased sympathetic): decrease VR.
• increased blood volume or decreased capacity (sympathetic stimulation): increase VR.
2- Right atrial pressure (RAP):
- Venous blood returns to right atrium.
- If right atrial pressure is high, it is difficult to drive venous blood back to right atrium.
- increased right atrial pressure opposes venous return.
N.B.: VR depends on difference between MSFP and RAP “pressure gradient for VR”.
3- Resistance to venous return (RVR):
- vascular resistance to venous blood
- calculated using Ohm law:

= 7- 0 / 5 = 1.4 mmHg/L/min.

➢ Venous Return Curve: relationship between RAP and VR :


A. Increasing RAP causes a decrease in VR
- When RAP reaches 7 mmHg VR decreases to zero (VR stops) “ the maximum value
RAP can rise to is the MSFP”

B. decreasing RAP causes VR to increase.


- if RAP decreases to -1 mmHg: VR no longer increases = plateau: negative pressure
causes collapse of veins preventing further increase in VR.

A.F. 2023 4
❖ Effect of changes in MSFP on venous return curve:
- Increasing MSFP (e.g. by increasing blood volume or decreasing capacity of
circulation) causes shift of curve up and to right: for same RAP, higher VR.
- decreasing MSFP causes VR curve shift down and left: for same RAP, lower VR.

❖ Effect of changes in RVR on venous return curve:


- Decreasing RVR: for same RAP VR is increased.
- Increasing RVR: for same RAP VR is decreased.
- N.B.: whatever value of RVR, venous return will be zero when RAP = MSFP.

A.F. 2023 5
➢ mechanisms (mechanical factors) help blood moving upwards towards heart:
1. Thoracic Pump: Negative intra pleural pressure helps venous return. But:
During inspiration During expiration
intra-pleural pressure – 8 mm Hg -4
intra-abdominal pressure raises to 6 mmHg due to 5
descent of diaphragm
gradient between abdominal increased = 6 - (-8) = 14 mm 5 – (-4) = 9 mmHg
and thoracic veins Hg
venous return is lower during expiration than inspiration

2. Heartbeat Effects:
Atrial suction Ventricular sucking
rapid ejection phase rapid filling phase
- atrioventricular ring is pulled down. - opening of tricuspid valve
- drop of atrial pressure sucking of - low ventricular pressure suck blood
blood into atria from atria & veins.
3. Muscle Pump: contraction of skeletal muscles surrounding Veins of limbs
compresses veins.
4. Venous Valves:
- intima veins is folded.
- allow flow towards heart but prevent retrograde flow.
- N.B.: If valves incompetent (e.g. in varicose veins), stasis of blood in lower limb.

➢ Interaction between Cardiac and Peripheral Vascular Factors in Control of CO:


• super-impose two curves:
1) Cardiac output curve. 2) Venous return curve

❖ Under steady states:


1. Venous return = cardiac output.
2. RAP is same for heart to pump its output, and for circulation to bring VR back.
• only point that fulfills this is intercept point (point A):
- Venous return = cardiac output = 5 L/min.
- RAP = 0 mmHg.

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1- If pumping of heart is increased (e.g. positive inotropic as digitalis) without
changing venous return:
shift CO curve up and to left, but CO will increase a little (point A to point B).
2- “Cardiovascular responses to exercise”: both CO & VR are increased
A. shift cardiac function curve up and left through:
a- Increasing inotropy and heart rate (sympathetic stimulation).
b- Decreasing afterload due to vasodilatation:
1) Mainly: local metabolites in contracting muscles
2) sympathetic vasodilator cholinergic fibers
- alone can only increase CO a little (from point A to point B).
B. venous return curve shift up and to right (increased VR): CO increase to much
higher level (intercept point C):
a- Increased MSFP:
1) sympathetic causes contraction of veins.
2) Increased muscle pumping action, thoracic and cardiac suction mechanisms.
3) Arteriolar dilation in contracting muscles
b- Decreased RVR: vasodilation of skeletal muscle vessels (by metabolites locally).

➢ Conclusion:
o Cardiac stimulation has little effect on cardiac output if acting alone.
o if circulatory function is additionally altered cardiac output can increase much higher.
o Explanation: Without changes in circulatory function, cardiac output is limited by the
return of blood to the heart.

A.F. 2023 7
Capillary Circulation
➢ Capillary Pressure:
• systemic capillaries:
o 35 mm Hg at the arteriolar end
o 15 mm Hg at the venous end,
o average capillary pressure of 25 mm Hg: exchange across the capillary wall.
• mean pulmonary capillary pressure is 10 mm Hg. (low value) important
to prevent filtration of fluid from pulmonary capillaries into alveoli
➢ Capillary Blood Flow:
• very slow (0.5 mm/s) because total cross-sectional area is large.
importance: enough time for exchange of materials between blood and ISF.
• Intermittent = “vasomotion”” : alternating contraction and relaxation of metarterioles
and precapillary sphincters in response to metabolites (↓O2, ↑CO2, lactic acid, K+).
a. In resting tissue: (6-12 times / minute)
- most of capillaries closed and blood flows through thoroughfare vessels.
- Metabolites accumulate and cause relaxation of metarterioles and sphincters.
- ↑ blood flow Washing metabolites: constriction of metarterioles and sphincters
b. In active tissues: concentration of metabolites increases.
1) opening of larger number of capillaries.
2) Vasomotion cycles.

➢ Equilibrium with Interstitial Fluid mechanisms of exchange of materials with ISF:


I. Diffusion: quantitatively most important. rate depends on:
A. Capillary permeability
B. Factors related to substance:
1) concentration gradient: directly proportional to rate of diffusion
2) Lipid solubility
3) Molecular size
II. Trans-Capillary Filtration (Bulk flow): “Starling Forces”.:
A. Mean forces tending to move fluid outwards:
1) Capillary hydrostatic pressure (Pc)
2) Interstitial colloid osmotic pressure (πi).
B. Mean forces tending to move fluid inwards:
1) Interstitial hydrostatic pressure (Pi)
2) Capillary colloid osmotic pressure (πc)

A.F. 2023 8
• Fluid movement = k [(Pc + πi) – (Pi + πc)]
A. Most capillaries as muscle capillary:
▪ arteriolar end: (37 + 0) – (1 + 25) = 11 mmHg: fluid moves out.
▪ venular end: (17 + 0) – (1 + 25) = - 9 mmHg: fluid moves into.
B. some other capillaries:
- Fluid may move out along entire length: in renal glomeruli.
- fluid may move in along entire length: in intestines and lungs.
• N.B.:
- interstitial colloid osmotic pressure (πi) is usually very small and can be ignored.
- capillary filtration coefficient (k) is proportionate to:
1) permeability of capillary wall
2) area available for filtration.
- 24 L filtered /day (85% reabsorbed at venous end & remainder returned via
lymphatics)
3. Vesicular Transport:
- for large lipid-insoluble molecules e.g., proteins.
- molecules engulfed by endothelial cells in vesicle that moves across endothelial cell
to be released at interstitial border by exocytosis.
- Importance: provide tissues with HMW molecules e.g. antibodies and hormones.
➢ Angiogenesis:
• developing new vessels by proliferation of endothelial cells (in adult)
• mechanism: ischemia: release of vascular endothelial growth factor

Lymphatic Circulation
• initial lymphatics drain to collecting lymphatics to large veins
• Drainage of lymph is helped by:
1. lymphatics have smooth muscle: peristaltic contraction (main factor)
2. Negative intra-thoracic pressure sucks lymph upwards.
3. Pulsations of neighboring arterioles.
4. Contraction of skeletal muscles surrounding lymphatics
5. Valves allow lymph to flow in only one direction
• Functions of lymphatics:
1. Drainage of excess filtered fluid from capillaries. (normal 2-4 L/day)
2. carry proteins from tissues (25% of plasma proteins returned /day)
3. Transport of absorbed long chain fatty acids and cholesterol from the intestine.
4. Removal of bacteria and their delivery to lymph nodes.
A.F. 2023 9
❖ Factors that determine ISF Volume:
1. capillary hydrostatic pressure.
2. Capillary osmotic pressure.
3. ISF pressure.
4. capillary filtration coefficient.
5. number of active capillaries.
6. lymph flow.
7. total extra-cellular (ECF) volume
8. ratio of pre-capillary to post-capillary venular resistance: pre-capillary constriction
lowers filtration pressure while post-capillary constriction elevates it.

Edema
❖ Definition: accumulation of fluid in interstitial space.
• N.B.: Because of gravity, ISF tends to accumulate in dependent parts (lower limbs in
standing position, and back in recumbent position)
• Causes of increased ISF volume and edema:
1- Increased Filtration Pressure:
a) Arteriolar dilation
b) Venular constriction = Increased venous pressure:
effect of gravity, increased total ECF volume, incompetent venous valves, venous
obstruction, and heart failure.
2- Decreased Osmotic Pressure Gradient Across Capillary:
a) Decreased plasma protein
1) Nutritional
2) liver cirrhosis (decreased synthesis)
3) kidney diseases as nephrosis (loss of plasma proteins in urine.)
b) Accumulation of osmotically active substances in ISF.
3- Increased Capillary Permeability: By Substance P, histamine, kinins in allergy
4- Inadequate Lymph Flow (lymphatic obstruction): high protein content associated
with inflammation and fibrosis (non-pitting edema) as elephantiasis.

A.F. 2023 10

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