ANNOUNCEMENTS
Email address for Dr. Levy:
[email protected]
Review Sessions for Exam (1/3/10):
Monday 1:10, 5:00, 8:00PM
Tuesday 4:00PM
Circulatory System
Blood Circulatory System
-arterial system
-capillaries
-venous system
Lymphatic System
-capillaries and ducts
-lymphatic organs
spleen, tonsils, thymus, lymph nodes
WEDNESDAY EXAM WILL COVER:
Connective Tissue- general
Cartilage
Bone
Adipose
Muscle
Nerve
Circulatory (arteries, veins, lymphatic vessels)
Arteries* and Veins: Three layers
tunica intima
squamous epithelium
basal lamina
subendothelial layer
*internal elastic membrane
tunica media
smooth muscle
*external elastic membrane
tunica adventitia
connective tissue
vasa vasorum
nervi vascularis
1
Arteries
elastic arteries (large: aorta, pulmonary vein)
reduced internal elastic membrane
tunica media- elastic fibers, smooth muscle
Venous System
Large veins: 3 layers not distinct
lumen larger than artery
lumen often collapsed
valves
muscular arteries (medium)
prominent internal elastic membrane
tunica media: >smooth muscle, <elastic fibers
small arteries/ arterioles
classified by # smooth muscle layers
arterioles 1-2; small artery 3-8
precapillary sphincter- smooth muscle
Medium veins: similar to large vein structure
adventenia thicker than media
several layers of muscle
Venules: postcapillary- fluid/cell loss - histamine
muscular: 1-2 layers of muscle
Artery
Vein
venule
Vein and valve
arteriole
Vein
3 layers not as distinct
lumen larger than artery
lumen often collapsed
valves
vein
capillary
Medium artery
2
Capillaries
- simple squamous epithelium
- no smooth muscle
- basal lamina (basement membrane)
- pericytes within basal lamina
- large surface area for exchange
- primary site of exchange for fluid
electrolytes, gases, and macromolecules
Types:
- continuous
- fenestrated
- discontinuous (sinusoidal)
Continuous Capillaries
- close cellular interconnections
•!junctional complexes
- permeable to small molecules <10nm in diameter
- most transport via pinocytotic vesicles
- muscle, skin, lungs, adipose tissue, CNS*,
retina and mammary glands
3
Pericyte: undifferentiated cell with multiple processes
gives rise to new endothelial cells
contained within basal lamina
Fenestrated Capillaries
- contain 'windows’,
fenestrations
- easy passage of larger molecules (10-100nm)
-! number of fenestrations varies with absorption
-! pinocytotic vesicles
-! diaphragms
-!nonmembranous
- basal lamina intact
- kidneys, pancreas,
gallbladder, intestine
4
Continuous capillary
Discontinuous (sinusoidal) Capillaries
- large diameter
- wide gaps between cells
- relatively free movement (even cells)
- gaps or missing basal lamina
- liver, spleen, ovaries, some endocrine glands
Fenestrated capillary
Blood flow through
Capillary Bed
-!controlled by
precapillary sphincters
-!smooth muscle band at
arteriole/capillary
PERMEABILITY
Low
High
Extremely
High
fajerpc.magnet.fsu.edu/.../ 30_Circulatory.htm
5
Fluid Movement across Capillary Wall:
Starling’s Law of Capillaries
-! Governed by Hydrostatic and Osmotic Pressures
HP > OP -->fluid moves from cap to tissue-->FILTRATION
occurs at arteriole end of capillary
HP < OP-->fluid moves from tissue to cap->REABSORPTION
occurs at venous end of capillary
Capillary Hydrostatic Pressure (HP): blood pressure
forces fluid OUT
Osmotic Pressure (OP): pressure due to plasma
proteins trapped in capillary
draws fluid IN
SMALL NET LOSS OF FLUID FROM BLOOD
Residual Fluid is taken up by Lymphatic Capillaries
-lymphatic ducts
-returned to blood
Lymphatic Capillaries and Vessels
-!blind end capillaries
-!interstitial fluid pressure
drives lymph into lymph
capillary
6
Lymphatic Capillaries and Vessels
The flow of lymph is regulated by:
1. Skeletal Muscle Pump.
2. Respiratory Pump.
3. Contraction of smooth
muscle in larger lymphatic
vessels walls
Skeletal muscle pump
www.cvphysiology.com/ Cardiac
%20Function/CF018.htm
4. Pressure on lymphatic vessels
by expansion/recoil of nearby
arteries
A. A 62 year old woman
has marked swelling of
ankles and lower legs.
Form a hypothesis
stating what you think
could account for this
symptom.
B. Design an
experiment that will
test your hypothesis.
Edema: accumulation of fluid in interstitial spaces
Hypotheses:
1.! Increased capillary hydrostatic pressure
- gravitational forces
- in heart failure
2.! Decreased osmotic pressure
- loss of plasma proteins from kidney or liver disease
3.! Increased capillary permeability
- inflammatory compounds- histamine, Anaphylaxis
- trauma- burns
4.! Lymphatic obstruction (as occurs in filariasis)
- side effect of surgery
- Elephantiasis (filariasis)
7
Lymphatic filariasis
(elephantiasis)
- caused by parasitic worm,
Wuchereria bancrofti
- transmitted to humans by
mosquitoe bites
- painful, disfiguring chronic
enlargement of arms, legs and
genitals
URINARY SYSTEM
•! Produces, stores & voids urine
--> control of blood volume
•! Removes toxic substances from blood
•! Electrolyte balance (Na+, K+, Ca++)
•! Hormone production: erythropoietin, renin
EXAM MATERIAL STOPS HERE
EXAM WILL COVER:
Connective Tissue- general
Cartilage
Bone
Adipose
Muscle
Nerve
Circulatory (arteries, veins, lymphatic vessels)
Kidneys: Produces Urine
blood filtration, selective
absorption of fluids, ions
Ureters: Transfers urine
kidneys --> bladder
Bladder: Stores & voids urine
Urethra: Transfers urine
bladder --> exterior
8
CORTEX
Capsule
Renal Corpuscle= Glomerulus+Bowman’s Capsule
•! Site of blood filtration
Hilum
•! Entrance of renal artery
•! Exit of renal vein
•! Exit of ureters
Associated tubules & collecting ducts
•! Site of absorption of water & small molecules
•! Continuous with the Medullary Rays
Renal Cortex
Renal Medulla
Renal Pelvis
CORTEX
CORTEX
9
Vasculature
Vasculature
Aorta ----> renal artery (RA) -----> hilum
Anterior and Posterior renal arteries
More branching->afferent arterioles (AA)
Glomerulus
Portal System: two capillary beds arranged in series
Portal System: two capillary beds arranged in series
Artery ---> Capillary bed ---> Capillary bed ---> Vein
Artery ---> Capillary bed ---> Capillary bed ---> Vein
Afferent --> glomerulus -->Efferent--> Peritubular
arteriole
arteriole
network
10
NEPHRON
Renal Corpuscle
•! Capillary glomerulus
•! Bowman’s capsule
•! Glomerular epithelium
•! Capsular epithelium
–! Viseral and Parietal Layers
–! Podocytes
»! Pedicels
»! Filtration slits
•! Bowman’s space
•! Poles
•! Vascular pole
•! Urinary pole: continuous with the proximal tubule
RENAL CORPUSCLE
11
NEPHRON
Renal Corpuscle
Initial blood filtration
- Glomerulus:
Fenestrated capillaries
- Bowman’s capsule
Glomerular filtration
Size filtration
•! Small molecules (uric acid, creatinine)
•! Substances with MW over 70 kDa are
excluded (generally albumin)
Visceral Layer:
Podocytes extend processes around capillaries
Interdigitating foot processes form filtration
slits
Charge selectivity
•! negatively charged molecules are limited from
passing to the Bowman’s space
Repelled by:
»!Heparan sulfate proteoglycan
»!Collagen
12
Filtration Slits
Slit diaphragms: span space between
foot processes of podocytes
http://www.jci.org/cgi/content/full/108/11/1583
http://www.jci.org/cgi/content/full/108/11/1583
Podocytes:
rich in actin filaments
slit diaphragm (filtration slit membrane)
bind to basal lamina
structural support to high pressure capillaries
development of glomerulus
Podocyte Process
Damage to Podocytes---> Excess filtration
Basal Lamina
13
http://www.jci.org/cgi/content/full/108/11/1583
Focal segmental glomerulosclerosis (FSGS)
NBA superstar Alonso Mourning
Families with inherited FSGS
- mutations in the ACTN4 gene
- encodes !-actinin-4
!-actinin-4:
- two identical anti-parallel peptides
http://www.bms.ed.ac.uk/research/others/smaciver/Cyto-Topics/alpha%20actinin.htm
Focal segmental glomerulosclerosis (FSGS)
Mutant !-actinin-4
- aggregation of proteins rather than pairing
- accelerated degradation
Wildtype
!-actinin-4
is evenly
distributed
in glomeruli
NEPHRON
Glomerulus
Initial blood filtration
Knockout mice that lacked Actn4 expression
- severely damaged podocytes
- progressive glomerular disease
Mutant "
!-actinin-4
aggregates
in
glomeruli
- Capillary tuft
- Bowman’s capsule
Cortical / medullary tubular system
•!Control of chemical composition
of blood
•!Urine salt concentration
(2004) A Protein's Role in Progressive Renal Disease. PLoS Biol 2(6): e194
14
Cortical / Medullary Tubular System
Convoluted Tubules
- Proximal
- Distal
CORTEX
Loop of Henle
- descending limb
- ascending limb
MEDULLA
Collecting duct
Medullary Pyramid
Cortex
Medulla
Papilla
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