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Lecture 75
Dr Shamshad
1. Describe the physiological anatomy of capillary
circulation.
2. Identify the values for normal capillary blood flow.
3. Discuss the dynamics for interstitial fluid formation.
4. Correlate this knowledge to edema formation.
2
Guyton & Hall,12th edition
3
• Thin & single-layered with highly permeable endothelial cells.
• A thin basement membrane Surrounds the outside of the capillary.
• Total thickness of capillary wall : 0.5 µm.
• Internal diameter: 4 - 9 µm.
Function :
 Serves as nutritional needs in all tissues.
 Exchange of gases, nutrients, & waste products.
 In most of the tissues has non nutritional need . Ex: kidneys, brain,
skin etc.
 Filtration-absorption thus maintain blood volume.
 Signaling in hormone transportation.
 Host defense as in platelets delivery.
Physiological anatomy of capillary circulation.
4
Values for normal capillary blood flow.
Over 10 billion capillaries
surface area : 500-700 sq mts
At any given time 5% of circulating blood vol present.
Pulse pr : 5 mmHg at arteriolar end & Zero at venous end.
Velocity of blood : 0.07cm/sec.
Transit time from arteriolar to venular end : 1-2 sec.
5
Values for normal capillary blood flow.
Capillary pr at rest
Glomeruli Liver Lungs Feet
70 mmHg 6 mmHg 8 mmHg 100 mmHg
Filtration Prevent the back
flow
Hydraulic conductivity of the capillaries cm3/sec/dyne
Brain (except
circum-
ventricular
organs
Skin Skeletal
muscle
Lung Heart GIt Glomerulu
s of kidney
3 100 250 340 860 13,000 15,000
Continuous type Fenestrate
d type
6
Defn : The blood vessels from first
order arteriole to the first order
venule.
Components : Single arteriole &
venule, b/w which extends a
network of true capillaries.
 May have metarteriole.
Precapillary sphincter:
 A smooth muscle fiber encircles
the capillary
Controls the entrance to the
capillary.
Microcirculation
7
1: Continuous: Most common
Interendothelial junctions: 10-15nm wide.
Ex : Skeletal muscles
2: Continuous with tight junctions: Allow only very small
molecules to pass thru.
Ex: Brain protective function
3: Fenestrated: Endothelial cells thin perforated with
fenestration/pores.
Ex:, Exocrine glands, Kidneys
4: Discontinuous :Clefts b/w capillary endothelial cells wide open
Fenestrated, sinusoidal with large gaps
Ex: sinusoids of liver
5: GIT: Midway between continuous and fenestrated type
Capillary types based on degree of leakiness
8
Starling forces:
Rate of filtration at any point along a capillary depends on a
balance of forces:
I: Capillary fluid:
1. Hydrostatic pr/capillary pr (Pc) Filtration
2. Oncotic/Colloidal pr (πc)Absorption (25-30mmHg)
II: Interstitial fluid:
1. Hydrostatic pressure (Pi)mostly remain constant
2. Oncotic pressure of interstitial fluid (πi)few IF proteins.
9
10
Plasma proteins maintain COP at 25-30mmHg
 Osmotic pr across the capillary wall is exerted by both colloidal
(Albumin, globulin etc.) and crystalloid substances (urea,
Sodium, glucose etc.,)
 Since capillary is completely permissible to crystalloid substances
they do not contribute to osmotic pr.
 Hence it is maintained by plasma protein especially albumin and
globulin at 25-30 mmHg.
Bulk Flow the most important mechanism for fluid
transfer driven by Starlings forces.
11
Filtration Absorption
Fluid movement = Kf [(Pc – Pi) – (Πc- Πi)]
Kf = filtration coefficient
12
Forces tending to move fluid outwards
Capillary pr (arterial end of capillary) 30 mmHg
Negative (free) IF pr 3mmHg
IF colloidal osmotic pr 8mmHg
Total outward pr 41mmHg
Forces tending to move fluid inwards
Plasma oncotic pr 28mmHg
Total inward pr 28mmHg
Summation of forces
Outward forces 41mmHg
Inward forces 28mmHg
Net filtration force +13mmHg
Forces Causing Filtration at the Arterial End of the Capillary
13
Forces Tending to Move Fluid Inwards
Plasma oncotic pr 28 mmHg
Total inward pr 28 mmHg
Forces tending to move fluid outwards
Capillary venous pr (venous end of capillary) 10 mmHg
Negative (free) IF pr 3 mmHg
IF colloidal osmotic pr 8 mmHg
Total outward pr 21 mmHg
Summation of forces
Inward forces 28 mmHg
Outward forces 21 mmHg
Net filtration force +7 mmHg
Forces causing Reabsorption at the Venous End of the Capillary
14
15
Defn: Intercellular / tissue fluid : Portion of ECF compartment
that is outside the vascular and lymph systems , bathing the
cells.
The plasma & the interstitial fluid intermingle through pores in
the blood capillaries which allow water & most dissolved
substances except protein to diffuse .
The exchange of material across the capillaries occurs at high rate
by diffusion in both direction.
Interstitial fluid
16
About 1/6th of the total volume of the
body spaces between cells.
Fluid in these spaces is interstitial fluid
Derived: by filtration and diffusion
from the capillaries.
Composition: same as plasma except
with lower concentrations of proteins
17
IF (99%) entrapped in the minute
spaces among the proteoglycan
filaments.
Has characteristics of a gel hence
also called tissue gel.
Fluid diffuses through the gel.
It moves molecule by molecule
from one place to another by
kinetic, thermal motion instead of
moving together.
18
“Free” Fluid in the Interstitium. (≤1% normally )
Small rivulets of “free” fluid and small free fluid vesicles are also
present, that can flow freely.
Significance ; In edema, these small pockets and rivulets of free
fluid expand tremendously.
Interstitial Fluid Pressure is negative due to pumping action by the
Lymphatic System.
Interstitial Fluid Pressure is (Average: −3 mm Hg) in Loose
subcutaneous tissue is Usually Sub atmospheric.
20
 The high content of proteins in the plasma accounts for its
higher osmotic pr compared to that of the IF which will attract
fluid & dissolved substances into the circulation from the tissue
spaces .
 Opposing this force is the hydrostatic pr of the blood
which tends to force fluids out of the circulation & into the
tissue spaces,
 This maintains the equilibrium under physiological condition .
21
 The IF enter lymphatic capillaries through loose junctions
between endothelial cells .
 Lymph flow back to the thoracic duct is promoted by
contraction of smooth muscle in wall of lymphatic vessels &
contraction of surrounding skeletal muscle .
 Failure of lymphatic drainage can lead to Edema .
Lymphatic circulation
22
• Most of the tissues have special lymph channels that drain excess
fluid directly from the interstitial spaces.
• Lymph is derived from interstitial fluid that flows into the
lymphatics
• Any factor that increases interstitial fluid pressure also increases
lymph flow if the lymph vessels are functioning normally.
Two primary factors determine lymph flow
1] The IF pressure
2] The activity of the lymphatic pump.
The rate of lymph flow is determined by the product of interstitial
fluid pressure times the activity of the lymphatic pump.
23
Accumulation of interstitial fluid in abnormally large amounts.
This abnormal accumulation of fluid may be specific organ vs
generalized (Anasarca).
Edema
24
Causes of increased interstitial fluid volume and edema
I:Increased filtration pressure:
i: arteriolar dilatation, ii : Venular constriction
iii : Increased venous pr : heart failure, incompetent valves, venous
obstruction, increased ECF vol, effect of gravity long standing,
pregnancy.
II: Decreased Oncotic pr gradient across capillary
i:Decreased PP level: liver failure, burns ,PEM, Nephrotic syndrome
(proteinuria)
ii: Accumulation of osmotically active substances in interstitial space
, after exercise or tissue injury
25
III : Increased capillary permeability
Tissue injury, allergy In urticaria ,inflammation
Substance P, Histamine & related , Kinins
IV : Inadequate lymph flow: Obstruction,
Legs and scrotum: elephantiasis
filariasis parasitic worms.
Metastasis by malignancies.
26
Causes in Capillaries
Decrease Oncotic pr :Decrease in PP (hypoprotenaemia).
decreases blood osmolarity  allowing fluid to escape from the
circulation to the interstitial space.
Causes:
Physiological : Pregnancy
Pathological: Decreases synthesis: impaired liver cells: hepatitis, Ca liver ,
malnutrition..
Excess lost: burns, dehydration , nephroscrosis..
Increase Hydrostatic pr: Venous End: Cardiac failure , DVT
leads to abnormal increase in IF vol .
Arterial end: Pre-capillary dilatation. Calcium channel blockers.
27
Increase capillary permeability: Histamines, bradykinin kinins
Result of capillary damage:
Pleura: Infections, tumors
Alveoli: Inhalation of noxious substance, Ex: chlorine gas etc
Capillary leaks
28
Interstitial Causes:
Varies from one organ to another:
Subcutaneous tissue: Sub-atmospheric (-2 mmHg)
Brain: Cerebral edema
Lung: Intra-alveolar=pulmonary edema, intra-pleural=pleural
effusion
Peritoneum=ascites
Hypothyroidism : Myxedema
29
Renin angiotensin aldosterone system(RAAS):
secondary hyperaldosteronism
ADH (Vasopressin)
ANP(Atrial Natriuretic Peptide)
Hormones involved in edema:
30
Jugular venous pressure
Elevated and pulsating:
Hypervolemia:
Then edema:
Due to increased capillary hydrostatic pressure:
Cardiac failure, or isolated RV (pulm HT)
Hypervolemia : by transfusion
31
Generalized edema without hypervolemia
Decreased capillary colloid oncotic pressure: liver, kidney,
catabolic states, malnutrition.
Increased interstitial colloid oncotic pressure: lymphatic.
Increase in capillary permeability: Inflammation, toxins, severe
anemia.

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Final lect 75 microcirculation 2020

  • 2. 1. Describe the physiological anatomy of capillary circulation. 2. Identify the values for normal capillary blood flow. 3. Discuss the dynamics for interstitial fluid formation. 4. Correlate this knowledge to edema formation. 2 Guyton & Hall,12th edition
  • 3. 3 • Thin & single-layered with highly permeable endothelial cells. • A thin basement membrane Surrounds the outside of the capillary. • Total thickness of capillary wall : 0.5 µm. • Internal diameter: 4 - 9 µm. Function :  Serves as nutritional needs in all tissues.  Exchange of gases, nutrients, & waste products.  In most of the tissues has non nutritional need . Ex: kidneys, brain, skin etc.  Filtration-absorption thus maintain blood volume.  Signaling in hormone transportation.  Host defense as in platelets delivery. Physiological anatomy of capillary circulation.
  • 4. 4 Values for normal capillary blood flow. Over 10 billion capillaries surface area : 500-700 sq mts At any given time 5% of circulating blood vol present. Pulse pr : 5 mmHg at arteriolar end & Zero at venous end. Velocity of blood : 0.07cm/sec. Transit time from arteriolar to venular end : 1-2 sec.
  • 5. 5 Values for normal capillary blood flow. Capillary pr at rest Glomeruli Liver Lungs Feet 70 mmHg 6 mmHg 8 mmHg 100 mmHg Filtration Prevent the back flow Hydraulic conductivity of the capillaries cm3/sec/dyne Brain (except circum- ventricular organs Skin Skeletal muscle Lung Heart GIt Glomerulu s of kidney 3 100 250 340 860 13,000 15,000 Continuous type Fenestrate d type
  • 6. 6 Defn : The blood vessels from first order arteriole to the first order venule. Components : Single arteriole & venule, b/w which extends a network of true capillaries.  May have metarteriole. Precapillary sphincter:  A smooth muscle fiber encircles the capillary Controls the entrance to the capillary. Microcirculation
  • 7. 7 1: Continuous: Most common Interendothelial junctions: 10-15nm wide. Ex : Skeletal muscles 2: Continuous with tight junctions: Allow only very small molecules to pass thru. Ex: Brain protective function 3: Fenestrated: Endothelial cells thin perforated with fenestration/pores. Ex:, Exocrine glands, Kidneys 4: Discontinuous :Clefts b/w capillary endothelial cells wide open Fenestrated, sinusoidal with large gaps Ex: sinusoids of liver 5: GIT: Midway between continuous and fenestrated type Capillary types based on degree of leakiness
  • 8. 8
  • 9. Starling forces: Rate of filtration at any point along a capillary depends on a balance of forces: I: Capillary fluid: 1. Hydrostatic pr/capillary pr (Pc) Filtration 2. Oncotic/Colloidal pr (πc)Absorption (25-30mmHg) II: Interstitial fluid: 1. Hydrostatic pressure (Pi)mostly remain constant 2. Oncotic pressure of interstitial fluid (πi)few IF proteins. 9
  • 10. 10 Plasma proteins maintain COP at 25-30mmHg  Osmotic pr across the capillary wall is exerted by both colloidal (Albumin, globulin etc.) and crystalloid substances (urea, Sodium, glucose etc.,)  Since capillary is completely permissible to crystalloid substances they do not contribute to osmotic pr.  Hence it is maintained by plasma protein especially albumin and globulin at 25-30 mmHg.
  • 11. Bulk Flow the most important mechanism for fluid transfer driven by Starlings forces. 11 Filtration Absorption Fluid movement = Kf [(Pc – Pi) – (Πc- Πi)] Kf = filtration coefficient
  • 12. 12 Forces tending to move fluid outwards Capillary pr (arterial end of capillary) 30 mmHg Negative (free) IF pr 3mmHg IF colloidal osmotic pr 8mmHg Total outward pr 41mmHg Forces tending to move fluid inwards Plasma oncotic pr 28mmHg Total inward pr 28mmHg Summation of forces Outward forces 41mmHg Inward forces 28mmHg Net filtration force +13mmHg Forces Causing Filtration at the Arterial End of the Capillary
  • 13. 13 Forces Tending to Move Fluid Inwards Plasma oncotic pr 28 mmHg Total inward pr 28 mmHg Forces tending to move fluid outwards Capillary venous pr (venous end of capillary) 10 mmHg Negative (free) IF pr 3 mmHg IF colloidal osmotic pr 8 mmHg Total outward pr 21 mmHg Summation of forces Inward forces 28 mmHg Outward forces 21 mmHg Net filtration force +7 mmHg Forces causing Reabsorption at the Venous End of the Capillary
  • 14. 14
  • 15. 15 Defn: Intercellular / tissue fluid : Portion of ECF compartment that is outside the vascular and lymph systems , bathing the cells. The plasma & the interstitial fluid intermingle through pores in the blood capillaries which allow water & most dissolved substances except protein to diffuse . The exchange of material across the capillaries occurs at high rate by diffusion in both direction. Interstitial fluid
  • 16. 16 About 1/6th of the total volume of the body spaces between cells. Fluid in these spaces is interstitial fluid Derived: by filtration and diffusion from the capillaries. Composition: same as plasma except with lower concentrations of proteins
  • 17. 17 IF (99%) entrapped in the minute spaces among the proteoglycan filaments. Has characteristics of a gel hence also called tissue gel. Fluid diffuses through the gel. It moves molecule by molecule from one place to another by kinetic, thermal motion instead of moving together.
  • 18. 18 “Free” Fluid in the Interstitium. (≤1% normally ) Small rivulets of “free” fluid and small free fluid vesicles are also present, that can flow freely. Significance ; In edema, these small pockets and rivulets of free fluid expand tremendously. Interstitial Fluid Pressure is negative due to pumping action by the Lymphatic System. Interstitial Fluid Pressure is (Average: −3 mm Hg) in Loose subcutaneous tissue is Usually Sub atmospheric.
  • 19. 20  The high content of proteins in the plasma accounts for its higher osmotic pr compared to that of the IF which will attract fluid & dissolved substances into the circulation from the tissue spaces .  Opposing this force is the hydrostatic pr of the blood which tends to force fluids out of the circulation & into the tissue spaces,  This maintains the equilibrium under physiological condition .
  • 20. 21  The IF enter lymphatic capillaries through loose junctions between endothelial cells .  Lymph flow back to the thoracic duct is promoted by contraction of smooth muscle in wall of lymphatic vessels & contraction of surrounding skeletal muscle .  Failure of lymphatic drainage can lead to Edema . Lymphatic circulation
  • 21. 22 • Most of the tissues have special lymph channels that drain excess fluid directly from the interstitial spaces. • Lymph is derived from interstitial fluid that flows into the lymphatics • Any factor that increases interstitial fluid pressure also increases lymph flow if the lymph vessels are functioning normally. Two primary factors determine lymph flow 1] The IF pressure 2] The activity of the lymphatic pump. The rate of lymph flow is determined by the product of interstitial fluid pressure times the activity of the lymphatic pump.
  • 22. 23 Accumulation of interstitial fluid in abnormally large amounts. This abnormal accumulation of fluid may be specific organ vs generalized (Anasarca). Edema
  • 23. 24 Causes of increased interstitial fluid volume and edema I:Increased filtration pressure: i: arteriolar dilatation, ii : Venular constriction iii : Increased venous pr : heart failure, incompetent valves, venous obstruction, increased ECF vol, effect of gravity long standing, pregnancy. II: Decreased Oncotic pr gradient across capillary i:Decreased PP level: liver failure, burns ,PEM, Nephrotic syndrome (proteinuria) ii: Accumulation of osmotically active substances in interstitial space , after exercise or tissue injury
  • 24. 25 III : Increased capillary permeability Tissue injury, allergy In urticaria ,inflammation Substance P, Histamine & related , Kinins IV : Inadequate lymph flow: Obstruction, Legs and scrotum: elephantiasis filariasis parasitic worms. Metastasis by malignancies.
  • 25. 26 Causes in Capillaries Decrease Oncotic pr :Decrease in PP (hypoprotenaemia). decreases blood osmolarity  allowing fluid to escape from the circulation to the interstitial space. Causes: Physiological : Pregnancy Pathological: Decreases synthesis: impaired liver cells: hepatitis, Ca liver , malnutrition.. Excess lost: burns, dehydration , nephroscrosis.. Increase Hydrostatic pr: Venous End: Cardiac failure , DVT leads to abnormal increase in IF vol . Arterial end: Pre-capillary dilatation. Calcium channel blockers.
  • 26. 27 Increase capillary permeability: Histamines, bradykinin kinins Result of capillary damage: Pleura: Infections, tumors Alveoli: Inhalation of noxious substance, Ex: chlorine gas etc Capillary leaks
  • 27. 28 Interstitial Causes: Varies from one organ to another: Subcutaneous tissue: Sub-atmospheric (-2 mmHg) Brain: Cerebral edema Lung: Intra-alveolar=pulmonary edema, intra-pleural=pleural effusion Peritoneum=ascites Hypothyroidism : Myxedema
  • 28. 29 Renin angiotensin aldosterone system(RAAS): secondary hyperaldosteronism ADH (Vasopressin) ANP(Atrial Natriuretic Peptide) Hormones involved in edema:
  • 29. 30 Jugular venous pressure Elevated and pulsating: Hypervolemia: Then edema: Due to increased capillary hydrostatic pressure: Cardiac failure, or isolated RV (pulm HT) Hypervolemia : by transfusion
  • 30. 31 Generalized edema without hypervolemia Decreased capillary colloid oncotic pressure: liver, kidney, catabolic states, malnutrition. Increased interstitial colloid oncotic pressure: lymphatic. Increase in capillary permeability: Inflammation, toxins, severe anemia.