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BIOEN 345: Blood vessel biology

and pathologies
Lecture 1: Blood Vessels, Flow Control
Guidelines to conduct on-line SPR 2020 classes:

No in-person classes, meetings, office hours or group project


sessions for BIOEN 345 for SPR 2020.
Classes and office hours will be conducted fully on-line.
Small-group projects and assignments, and these must also be
conducted 100% remotely.
No in-person team work is allowed, on or off-campus.

Recording of BIOEN345 will be made available to all students


in the class. The recordings will be available for viewing for a
12-hour period following the class scheduled time,
approximately from 6 pm to 6 am PDT the following day. The
recordings must not be shared with students outside
BIOEN345. We will be monitoring the viewing.
FAILURE ANALYSIS: Blood vessel biology, Failures, and Vascular Therapeutics
Date Room Instructor Lecture/Lab Topic Reading Assignment
Blood vessels and blood
22-Apr Online Scatena Lecture
flow Ch. 15 Silverthorn,
24-Apr Online TA - Clark Lab 1 Flow Simulation
Blood composition and Lab 2 instructions
27-Apr Online Scatena Lecture
coagulation Ch.16 Silverthorn out

29-Apr Online Scatena Lecture Vascularization and


vascularization therapies

1-May Online TA - Clark Lab 2 Lab 2 report due


Engineered Angiogenesis
Pathologic basis of
disease Ch 12 or
Vessel pathologies, Lab 1 report due
4-May Online Scatena Lecture therapies and devices
pathophysiology of
heart disease Ch 5
Call for LOI out
and 8
Control of blood
6-May Online Scatena Lecture pressure and lymphatic
system Ch. 15 Silverthorn,
TA - Clark,
Design Lab - Proposal
8-May Online Graders, Lab 3 presentation
Lab 3 report due
Scatena
TA - Clark,
11-May Online Evaluation Midterm 2
Scatena

Scatena office hours: Wednesday 10:00 AM-Noon


Labs
• Lab 1: Computer lab – study the flow pattern in different diseased
blood vessels–April 24th
• Lab report 1 (due May 4th)
• Lab 2: Engineered Angiogenesis – May 1st
• Lab report 2 (due May 1st)
• Lab 3: Design lab –design a diagnostic, or treatment tool for a
vascular disease – May 8th
• The group will be assigned a disease
• Lab presentation + 1 page LOI proposal (due April May 8th)
• 10 minutes presentation to cover the context of disease,
current diagnostic/treatment methods,
challenges/gap/misdiagnostic/low-efficiency treatment, your
method, and potential application
Letter of Intent (LOI) format
1.Font size: 12 Times New Roman
2.Page length: 1 page
3.Format
• Title, and participants
• Goal
• Background (context of disease, current
methods, challenges)
• Your approach
• Feasibility
• Innovation and impact
https://archive.org/de https://alliance-
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Grading structure

Assignment % of total Points of total


grade grade
Midterm 2 40% 60
Lab report 1 23.3% 35
Lab report 2 13.4% 20
Lab 3 LOI and 23.3% 35
presentation
Total 100% 150
Cardiovascular System: a closed
circuit of transport
Possible failures
Blood vessel failure:
- occlusion (break/block-> heart pump changes)
- change of resistance
- loss of elastic properties - no control of dilating
or constricting
- regression and overgrow (ischemia, retinopathy,
cancer)

Blood failure:
- blood cells structure change, dysfunction
- coagulation factors
- blood cell activation
Cardiovascular System: Tissue
Structure
Blood Vessels - Layers

Capillaries
Immune cells
fibroblasts
Blood Vessel Structure

Elastic
Muscular

+ pericytes

+ pericytes
Vein
Muscular vein

http://www.histology.leeds.ac.uk/circulatory/veins.php
Elastic artery
Muscular artery
Arteriole/Small artery

https://www.studyblue.com/notes/note/n/histology-of-veins-
arteries--lymphatics/deck/11053853
Capillary

http://www.columbia.edu/itc/hs/medical/sbpm_histology_old/lab/
lab02_micrograph.html
Veins

Venule
Vein

Muscular Vein

http://www.histology.leeds.ac.uk/circulatory/veins.php
Vein - Valve

http://www.courseweb.uottawa.ca/medicine-
histology/english/cardiovascular/histologybloodvessels.htm
Structure à Function

• What role does the smooth muscle play in the vasculature?


• What role does the elastic matrix play in the vasculature?
Silverthorn
Silverthorn
Hemodynamics

• Flow
• Pressure gradient (DP)
• Resistance (R)

Flow µ DP/R

R depends on radius and length of the


vessel and viscosity of the fluid
• R= 8hl/p r4
• h = viscosity, l = length of vessel, r = radius
22
Velocity of Blood Flow
Velocity of flow depends on total cross-
sectional area of the vessels

Velocity Flow rate


=
of Flow Cross-sectional
area

Figure 15-17

Silverthorn
Functional Model of the Cardiovascular System –
unidirectional blood flow
• What role does the smooth muscle play in the vasculature?
• What role does the elastic matrix play in the vasculature?

precapillary resist. vessels

Figure 15-1

Silverthorn
Blood Flow
Blood flow through individual blood vessels is determined by vessel’s
resistance to flow
Flow µ 1/resistance

Figure 15-14a

Silverthorn
Blood Flow

When? How?
What is the mechanism and how is it triggered and regulated?
Figure 15-14b

Silverthorn 26
Control of Blood Flow

• Local blood flow is regulated in proportion to the


metabolic demand in most tissues
• Short term control involves vasodilatation
vasoconstriction of precapillary resist. vessels
• arterioles, metarterioles, pre-capillary
sphincters
• Long term control involves changes in tissue
vascularity
• formation or dissolution of vessels
• vascular endothelial growth factor & others

Silverthorn 27
Smooth muscle cells

Silverthorn
Local Control of Flow (short term)
• vasoconstriction/vasodilatation of pre-
capillary resistance vessels
– Active tissue release local vasodilator
(metabolites) which relax vascular smooth
muscle
Vasoconstriction Vasodilation
• Endothelins • histamine
• hydrogen ions
• PGE & PGI series prostaglandins
• Nitric Oxide
• carbon dioxide
• Adenosine
29
Norepinephrine - Systemic Control (short term)
Tonic control of arteriolar diameter

Figure 15-12
Silverthorn 30
Control of Flow (long term)

• Changes in tissue vascularity


• On going day to day reconstruction of the vascular system

• Angiogenesis-production of new microvessels


• Arteriogenesis (exercise)
• shear stress caused by enhanced blood flow velocity associated
with partial occlusion
• Angiogenic factors (pathological growth)
• small peptides-stimulate growth of new vessels
• VEGF (vascular endothelial growth factor)

31
Flow µ DP/R
Volume-Pressure relationships

• A D volume µ D pressure
• Distensibility is the ability of a vessel to stretch (distend): =
D Vol/D Pressure X Initial. Vol
• Compliance is the ability of a vessel to stretch and hold volume: =
D Vol/D Pressure

• In systemic arteries a small D volume is associated with a large D


pressure
• In systemic veins a large D volume is associated with a small D
pressure
• Veins are about 8 X more distensible and 24 X more compliant
than systemic arteries

32
Artery vs vein
Extracellular matrix (elastin)

Silverthorn 33
Arteries Arterioles Capillaries Veins

Central venous compartment: volume enclosed by the right atrium and great veins in
the thorax
Arteries

Arterioles

Ventricle
Capillaries
Atrium

Veins
Central venous compartment

Peripheral venous compartment

Mohrman and Heller, Cardiovascular Physiology


Flow µ DP/R

Regulation of blood pressure (BP)


Why?
• To ensure adequate blood flow to each organ
• autoregulation of individual organs works best with a steady pressure
at input
• most important function – maintain a steady pressure

• To avoid competition among the organs for blood supply

• To adjust BP to bodily need (sleep, exercise)

• To keep BP high enough to supply all organs (>80mmHg) but low enough to
avoid damage to vasculature

35
Pressure in Systemic Circulation
Blood pressure is highest in the arteries and decreases continuously as
it flows through the circulatory system

MAP = diastolic P + 1/3(systolic


P – diastolic P)
Where
systolic P – diastolic P=pulse
pressure

Figure 15-5

Silverthorn 36
How?
Concept of Contents vs. Container
Contents
• blood volume
Container
• blood vessels

Control of blood pressure is accomplished by either affecting


vascular tone or blood volume

37
Factors that Influence Mean Arterial Pressure

Venous reservoir

hemorrhage
Figure 15-10

Silverthorn 38
Mean arterial pressure is a function of cardiac output and
resistance in the arterioles= the volume produced by the heart
times vessel radius (vasodilation/vasoconstriction)

Figure 15-8

Silverthorn 39
Systolic Blood Pressure
• The maximum pressure in the systemic arteries
• Pressure peaks as blood is ejected from the left ventricle into the aorta

• Inflow volume from the Left Ventricle typically occurs at a faster rate then
peripheral runoff out the arterial tree during systole causing arterial
Pressure to Ý
Silverthorn 40
Diastolic Blood Pressure
• The minimum pressure in the systemic arteries

• How low the pressure falls is dependent on 2 factors


• Cycle length (CL) inversely proportional to Diastolic Blood Pressure (DBP)
• Ý CL will ⇓DBP
• Total peripheral resistance (TPR) proportional to DBP
• Ý TPR will Ý DBP
• During exercise DBP may not change much due to ⇓ CL is offset by ⇓ in TPR.
Silverthorn 41
Blood Pressure
Blood pressure control involves the nervous,
cardiovascular, and renal systems

Figure 15-9 42
Silverthorn
Fluid Exchange at a Capillary
Hydrostatic pressure and osmotic pressure regulate bulk flow

What factors will influence this


exchange, and how?
Figure 15-18a

Silverthorn 43
Silverthorn
Lab 1 –Flow lab

Silverthorn

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