Cardio and Smooth Muscle Histology

Question 1

how do nuclei appear in cardiac muscle?

Answer 1

1 or 2 centrally located nuclei

Question 2

in a cross section of cardiac vs skeleton muscle, how do cells appear histologically?

Answer 2

cross-section of cardiac muscle shows cell profiles in a variety of shapes, while skeletal muscle is much more uniform

also the CT between cells is more abundant and less organized in cardiac muscle

Question 3

what are 2 features of cardiac muscle that can differentiate it histologically from skeletal muscle?

Answer 3

cardiac muscle has branching fibers, while skeletal does not

cardiac muscle contains intercalated discs at the Z line (T-tubules also found here)

*note cardiac muscle also has a higher abundance of mitochondria

Question 4

what are the 3 components of intercalated discs in cardiac muscle?

Answer 4

cell-cell junction found at Z line

1. fascia adherens: actin filaments, transverse component
2. spot desmosomes: intermediate filaments, lateral component
3. gap junction: lateral component

Question 5

how can you identify Purkinje fibers of the heart histologically?

Answer 5

Purkinje fibers are larger and paler than ordinary myocytes

pale cytoplasm due to high glycogen content

they are found between endocardium and myocardium

Question 6

what are the basic steps of contraction of cardiac muscle?

Answer 6

1. action potential via pacemaker cells in SA node or AV node
2. depolarization spreads over plasma membrane of cardiomyocytes to T tubules, causing extracellular Ca2+ to enter (via L/long-type calcium channel for sustained contraction)
3. rise in cytoplasmic Ca2+ opens Ca2+ channels in SER
4. Ca2+ is released from SER and it enters sarcoplasma (calcium-induced calcium release)
5. contraction follows similar to skeletal muscle
6. Ca2+ returns to SER and binds calsequestrin

Question 7

how does smooth muscle appear histologically?

Answer 7

spindle-shaped, tapering cell without striations

1 centrally located nuclei

very little CT between cells (cell borders indistinguishable)

caveolae invaginations of plasma membrane - stimulate ion channels and receptors

alpha-actinin cytoplasmic dense bodies - actin filament attachment sites

Question 8

which type of muscle cells can divide and secrete proteins of the extracellular matrix?

Answer 8

smooth muscle

Question 9

how does smooth muscle contraction occur?

Answer 9

1. depolarization or hormonal stimulation causes increase in cytosol Ca2+ (underdeveloped SR, so Ca2+ must come form extracellular source)
2. Ca2+ binds calmodulin, complex binds myosin light chain kinase (MLCK)
3. myosin changes from inactive/folded to active/unfolded state and phosphorylation allows it to attach to actin (slower cross-bridge than skeletal muscle)

*does not contain troponin, but does contain tropomyosin which binds/stabilizes actin filaments
*no sarcomeres

Question 10

in smooth muscle, actin and associated myosin attach to dense bodies, which are attached to the plasma membrane through ___ and ___ intermediate filaments

Answer 10

desmin and vimentin intermediate filaments attach dense bodies of smooth muscle to plasma membrane

when actin-myosin complex contracts, their attachment to the dense bodies determines cell shortening

Question 11

which side of the heart is a higher pressure system?

Answer 11

systemic (left) side is higher pressure than pulmonary (right) side

this makes sense because the left side has to pump blood with enough force for it to circulate the entire body!

Question 12

what are the 3 tissue layers of the heart?

Answer 12

outermost: epicardium, contains coronary blood vessels embedded in adipose

middle: myocardium, with communicating/gap junctions/ nexus between myocytes

innermost: endocardium, simple squamous epithelium with thin layer of CT

Question 13

cardiac muscle is attached to a fibrous _____ which reinforces the bases of valves and insulates the ventricles from electrical activity in the atria

Answer 13

cardiac skeleton

Question 14

what are the 2 hormones secreted from myocytes, which myocytes secrete them, and what do they do?

Answer 14

myocytes secrete hypotensive hormones that promote natriuresis (secretion of salt, water follows) by kidneys

atrial myocytes secrete ANP (atrial natriuretic peptide) from granules in response to volume expansion

ventricle myocytes produce BNP (B-type natriuretic peptide), which causes a more slow effect because it must be unregulated first (not in granules)

Question 15

contrast the natriuretic hormones secreted by atrial and ventricle myocytes

Answer 15

natriuresis = excretion of salt (and water follows) by kidneys

atrial: ANP (atrial natriuretic peptide), in response to volume expansion, secreted from pre-formed cytoplasmic granules

ventricle: in response to volume expansion and pressure overload, secrete proBNP (B-type natriuretic peptide) which is cleaved in blood to active BNP - not stored in granules, so production must be up regulated first —> slower response

Question 16

blood levels of what cardiac hormone can be used as an important diagnostic sign of congestive heart failure?

Answer 16

congestive heart failure: heart is unable to maintain sufficient output for metabolic requirements

BNP (B-type natriuretic peptide) produced by ventricle myocytes (as opposed to ANP by atrial myocytes) is a key diagnostic sign…

…produced in response to volume expansion and pressure overload as proBNP, cleaved in blood to active BNP

not in granules, must be up-regulated first

Question 17

what is the function of cardiac C-type natriuretic peptide hormone, and where is it released from?

Answer 17

vascular endothelium release C-type natriuretic peptide hormone

promotes clearance of types A (ANP, atrial myocytes) and B (BNP, ventricle myocytes)

remember that ANP and BNP are hypotensive hormones that promote natriuresis (salt excretion) - definitely don’t want too much of that

Question 18

how does pressure/speed of flow, permeability, elasticity, and total area compare between large arteries, capillaries, and veins?

Answer 18

large arteries: HIGH pressure/speed of flow, low permeability, high elasticity, low total area
*makes sense because arteries have to pump blood through the whole body

capillaries: low pressure/speed of flow, low elasticity (none), HIGH permeability, HIGH total area
*makes sense because capillary beds are large and function in exchange

veins: low pressure/speed of flow, low permeability, mid-elasticity, mid-total area

Question 19

what are the 3 layes (tunica) of blood vessels?

Answer 19

innermost: tunica intima - simple squamous endothelium, basement membrane, connective tissue, internal elastic lamina

middle: tunica media - smooth muscle, external elastic lamina, well developed in arteries

outermost: tunica adventitia - connective tissue, vaso vasorum/nervi vasorum (supply vessels themselves), well developed in large veins

*note that inner part of blood vessels is avascular because blood flow would damage small vessels (nutrients by diffusion), while outer layer is vascular zone

Question 20

what makes up the perivascular/periarteriolar plexus of blood vessels?

Answer 20

vaso vasorum and nervi vascularis/vasorum - the vessels and nerves of the vessels

note the nervi vasorum innervate smooth muscle cells of vessels AND travel to destinations on internal organs

this plexus is found in the tunica adventitia (outermost layer)

Question 21

how is the elastic tissue and smooth muscle arranged in arterial walls?

Answer 21

circular pattern

Question 22

where does the elastic tissue in large elastic arteries come from?

Answer 22

smooth muscle cells in the tunica media produce the elastic tissue (secretory function)

the elastic tissue is arranged in both fibers and sheets (lamina) in the intima and media, and the elastic lamina has holes to allow diffusion of substances

Question 23

as arteries get smaller the have more ____ and less _____ in the tunica media

Answer 23

as arteries get smaller the have more SMOOTH MUSCLE and less ELASTIC TISSUE in the tunica media

this is to help direct blood flow

Question 24

describe the transition from arteries to capillaries

Answer 24

arteries decrease in size to arterioles, which have relatively thick walls compared to lumen size - this confers high resistance to blood flow, which is responsible for drop in arterial pressure before blood enters capillary bed

metarterioles serve as transition between arterioles and capillary bed, with incomplete layer of smooth muscle, and smooth muscle cells arranged longitudinally

*metartioles can also continue as preferential/thoroughfare channels through a vascular bed that allow capillaries to be bypassed

Question 25

_____ of smooth muscle cells controls the entrance to the capillary bed and regulates the amount of blood that enters

Answer 25

pre-capillary sphincter

Question 26

what allows endothelial cells to regulate capillary diameter?

Answer 26

actin and myosin in their cytoplasm

pericytes are contractile cells (also stem cells) found at intervals along capillaries

Question 27

what are the 3 types of capillaries?

Answer 27

1. continuous: least permeable (zona occludens) - blood-brain barrier, blood-thymus barrier, blood-testis barrier
2. fenestrated: may be covered by a diaphragm - viscera, endocrine glands, renal glomerulus
3. sinusoid (discontinuous): most permeable, lined by fixed macrophages - liver, spleen, bone marrow

Question 28

what are 2 forms of transportation in/out of capillaries?

Answer 28

1. hydrostatic pressure forces plasma out of capillaries and into interstitial tissues… at venous end osmotic pressure (from large proteins that can’t escape) draws fluid back in
2. transcytosis via pinocytotic vesicles: transports larger molecules

Question 29

what determines blood flow in veins?

Answer 29

blood flow in veins is independent of blood pressure in arteries

muscular activity in the lower limb and movement of abdominal/thoracic organs is responsible for squeezing veins to propel blood, and valves in veins inferior to the heart prevent back-flow

Question 30

T/F: venules are as permeable as capillaries

Answer 30

true!

leukocytes often leave circulation via diapedisis from venules to enter tissues

[recall that in lymph nodes, HEV/high endothelial venules facilitate migration of T cells into lymph nodes]

Question 31

how could you distinguish a large vein inferior to the heart from an artery histologically?

Answer 31

large veins inferior to the heart will have large bundles of smooth muscle, like arteries have

however, arteries will have an internal elastic lamina while veins will not! Veins are low-pressure vessels, no need for elasticity

Question 32

what determines the capacitance of veins?

Answer 32

capacitance = ability to store blood

most circulating blood volume is within venous system

distensibility of the walls of veins allows veins to store large amounts of blood with little change in pressure (low pressure system)

Question 33

what is the function of atriovenous (AV) shunts of capillary beds?

Answer 33

allow blood to bypass a capillary bed, such as in the skin to conserve heat

shunts have thick muscular walls and are innervated by the automatic nervous system

Question 34

what is structurally different about lymphatic capillaries compared to blood capillaries?

Answer 34

lymphatic capillaries pick up tissue fluid not taken up by venous end of capillaries (~10%) and deliver to lymph nodes for filtration

lymphatic capillaries have discontinuous basement membranes or are missing altogether so that large proteins and particulates can easily enter

most numbers in CT of skin, mucous membranes, respiratory tract, GI, and UG tract

Question 35

describe what is meant by the “metabolic blood brain barrier”

Answer 35

some endothelial cells have metabolic properties that allow them to activate/inactivate materials before they pass through

the metabolic blood brain barrier modifies some substances to make them less available to the CNS

ex: anti-Parkinson drug L-dopa is decarboxylated in endothelial cells

Question 36

what is the function of acetyl cholinesterase (AChE) and monoamine oxidase (MAO), enzymes found within endothelial cells?

Answer 36

AChE and MAO inactivate neurotransmitters

example of how endothelial cells act as metabolic as well as physical barrier

Question 37

most endothelial cells contain ________, which converts vaso-inactive angiotensin I to angiotensin II, a potent vasoconstrictor which also inactivates the vasodilator ______

Answer 37

most endothelial cells contain ACE (angiotensin converting enzyme), which converts vaso-inactive angiotensin I to angiotensin II, a potent vasoconstrictor which also inactivates the vasodilator BRADYKININ

Question 38

how does the anti-angina drug nitroglycerin work?

Answer 38

nitroglycerin is metabolized by endothelial cells to nitric oxide (NO) and acts as a vasodilator on the coronary arteries

Question 39

how do endothelial cells allow platelets to aggregate, which don’t normally stick to EC due to heparin sulfate (polyanionic)?

Answer 39

damaged EC produce Factor VIII (Von Willebrand’s Factor), which is needed for platelets to adhere to sub-endothelial CT

Factor VIII is stored in Weibel-Palade bodies

recall that Factor VIII deficiency (von Willebrand’s disease) leads to excessive bleeding

Question 40

what do tissue cells deprived of oxygen secrete to increase the transcription of VEGF and induce angiogenesis?

Answer 40

hypoxia-inducible factor I (HIF-1): gene regulatory protein which increases transcription of VEGF (vascular endothelial growth factor)

—> proteases dissolve basement membrane and endothelial cells proliferate and mature

Question 41

claudication

Answer 41

claudication: pain in muscles on exertion due to lack of oxygen

symptom of atherosclerosis