Test 3 - 2 Flashcards
1
Q
Blood vessel tunics
A
- Intima
- media
- adventitia
2
Q
tunica intima
A
- Endothelium and basal lamina
- Subendothelial layer
- Loose connective tissue
- Scattered fibroblasts and, in arteries, occasional smooth muscle cells
- Internal elastic lamina (membrane): Composed of elastin; Contains fenestrae for diffusion of substances
3
Q
tunica media
A
- Concentric layers of smooth muscle cells
- Variable amounts of: Elastin, elastic fibers, fibronectin and fibrillin-1; Reticular fibers; Proteoglycans
- External elastic lamina (membrane) comprised of elastin
4
Q
tunica adventitia
A
- Connective tissue layer
- Type I collagen fibers
- Elastic fibers
- Fibroblasts
5
Q
components of the cardiovascular system
A
blood vessel system, lymphatic system
6
Q
Vasa vasorum (vessels of the vessels)
A
Arteries - outer wall mostly vs. veins-gets right up to tunica intima (poorer oxygen conc and diffusion need to go deeper)
-Required for vessels greater than 1 mm in diameter
vessels that supply blood to blood vessels
7
Q
syphilis and vasa vasorum:
A
Vasa vasorum of the ascending aorta become inflamed in syphilis. This results in endarteritis and periarteritis of the vasa vasorum, which then eventually become obliterated. This causes focal necrosis and scarring of the media and degeneration of the elastic lamellae. The focal scarring of the media results in depressions that can be observed on the surface of the intima. Consequently, a tree bark appearance is imprinted on the intimal surface.
8
Q
atherosclerosis and vasa vasorum
A
-In atherosclerosis, vasa vasorum contribute to the angiogenesis and inflammation of the diseased vascular wall (this includes intimal thickening).
9
Q
Innervation of BV
A
- network of autonomic nerve fibers known as the nervi vasorum or vascularis
- ARTERIES: nerve endings do not penetrate the media;
- VEINS: Nerve ending in adventitia and media; density is less than arteries
-mainly sympathetic fibers but some parasymp in vascular beds
10
Q
Endothelial cells
A
- Flattened, polygonal cells; long axis is in direction of blood vessel
- Intercellular juntions between endothelial cells and to basal lamina. Also, myoendothelial junction. Shear stress exerted by blood flow increases endothelial [Ca2+] producing endothelial cell hyperpolarization. conducted to vascular smooth muscle via gap junctions=hyperpolarization=vasodilation.
- Contain Weibel – Palade bodies. Bodies contain: Von Willebrand factor (coagulating factor VIII); Tissue plasminogen activator; Interleukin 8; P-selectin attachment for leukocytes to move into ECM; Others: Promote/inhibit blood coagulation; Modulate smooth muscle activity (ex., endothelin and NO); Regulate inflammatory cell traffic; Transport – numerous pinocytotic vesicles; Regulate angiogenesis
- microvilli
11
Q
Elastic (large) arteries
A
- Elastic lamellae increase with age
- Aging also causes mild to moderate intimal fibrosis and fragmentation of elastic lamellae in the media
- Marfan’s syndrome severe elastic medial fragmentation with GAG area - lose struts connecting adjacent lamelae.
- MEDIA IS THINK IN ARTERY
- INTERNAL AND EXTENAL ELASTIC MEMBRANES BETTER DEVELOPED
12
Q
muscular (medium) arteries
A
- Aging also results in progressive intimal fibrosis (thickening) and alterations of elastic elements
- Aneurysm - circle of Willis
13
Q
Arteroiles
A
smaller-ish that meduium?
-BLOOD PRESSURE CONTROL HERE
14
Q
Metarterioles
A
- Vessels between arterioles and capillaries
- Media is composed of a discontinuous layer of smooth muscle
- Help to regulate blood flow into the capillary bed
- muscle sphincters determines blood distribution
15
Q
Capillaries
A
1) Tunica intima: Endothelium & Basal lamina
2) Tunica media (true media is absent) - Pericytes relate to the position of this layer. Pericytes contribute to the formation of scar tissue in the CNS and perhaps in other organs.
3) Tunica adventitia – ABSENT
Facilitate exchange bw blood and tissues
16
Q
Three types of capillaries
A
- Continuous (location – CNS, muscle, and lungs)
- Fenestrated (location – kidney, intestines, endocrine glands)
- Sinusoidal (location – spleen, liver, and bone marrow)
17
Q
Pericytes
A
- Mesenchymal cells
- contractile
- Can transform into smooth muscle cells and fibroblasts
18
Q
thickest layer in vein
A
adventitia
19
Q
continuous capillaries
A
- tight junctions bw endothelial cells - with marginal folds (help with defense cell movement)
- lack pores (or fenestrae)
- contain numerous pinocytotic vesicles
- well dev basal lamina
- in brain, muscle, CT, and exocrine glands, lungs
20
Q
fenestrated capillaries
A
- fanestrae (pores) are present in endothelial walls-pores have thin diaphragm
- continuous basal lamina
- subclasses-witho r without diaphragm in pores
- in exchanging tissues: kidney (glomerlus without diaphragm), endocrine, intestines,
21
Q
sinusoidal capillaries
A
- discontinuous endothelial lining - large openings
- discontinuous or absent basal lamina
- macrophages present
- incell exchange itssues: red bone marrow, liver, spleen, adrenal cortex
22
Q
longitudinal bundle of smooth muscle is found in what and what layer?
A
adventitia of IVC, SVC, brachiocephalic, renal, iliac veins
23
Q
age related change to muscular arteries
A
tunica intima gets thicker and media thins
24
Q
arteriole distinguishing fact
A
if wall is about as thick as the lumen
25
venules
smallest - no smooth muscle but has pericytic - can be leaky during inflamation
-usually irght next to arterioles
venules join to form muscular venules
26
post capillary venules
can be leaky - help with cell migration-finds marginal folds to pass through intercellular junction
27
medium vein
thicker wall and better developed tunica media with smooth muscles (still weak)
tunica adventitia is thickest layer
no internal and external elastic membrane
28
large vein
like brachiocephalic, portal vein
thin tunica media
circumpherential muscle
start to see longitudinal smooth muscle in adventitia
29
vasculogenesis in adults occurs by three methods:
from endothelial precursor cells (EPCs)
from pre-existing vessels
from tumor angiogenesis (uses both mechnanisms)
30
vasculogenesis from endothelial precursor cells:
- EPCs are angioblast-like cells that reside in the red bone marrow of adults and non-bone marrow niches
- When necessary, EPCs mobilize from their niches and migrate to the site where blood vessel formation is to occur. The mechanism by which they home in on this site remains unclear.
31
EPC mech for vasculogensis uses:
- Replaces lost endothelial cells
- Re-endothelization of vascular implants
- Neovascularization of ischemic organs, wounds, and tumors
32
Pre-existing BV formation of BV steps
- Vasodilation (NO) and increased vascular permeability (VEGF) of pre-existing (parent) vessel
- Proteolytic degradation of the basal lamina of the parent vessel by metalloproteinases. Endothelial cells shed their cell-to-cell contacts (intercellular junctions). This loss of cell-to-cell contact is mediated by plasminogen activator.
- Migration and proliferation of endothelial cells which have disrupted their cell-to-cell contacts. The migration and proliferation is induced by proangiogenic factors (e.g., VEGF and angiopoietin). Fibroblast growth factor-2 can also mediate endothelial cell migration and proliferation.
- Endothelial cells mature into an endothelial capillary tube.
- Elaboration of basal lamina and recruitment of periendothelial cells. (pericytes for capillaries and pericytic venules and smooth muscle cells for larger vessels). Elaboration of basal lamina elements is mediated by TGF-β (tumor growth factor). Recruitment of periendothelial cells is mediated by the interaction of Ang 1 with the Tie2 receptor on endothelial cells. PDGR (platelet-derived growth factor) induces recruitment of smooth muscle cells. Angiopoietin (Ang) 2 is involved in the stabilization process. Ang2 bound to Tie2, in the absence of growth factors, makes the endothelial cell more responsive to antiangiogenic factors.
33
tumor endothelial marker for tumor vessels
tumor endothelial marker 8
34
Proangiogenesis for clinical benefit
```
Myocardial ischemia
Peripheral ischemia
Cerebral ischemia
Wound healing and fracture repair
Reconstructive surgery
Transplantation of islets of Langerhans
```
35
Antiangiogenesis for clinical benefit
```
Tumor growth and metastases
Ocular neovascularization
Hemangiomas
Rheumatoid arthritis
Atherosclerotic plaque neovascularization
Birth control
```
36
vascular remodeling is driven by:
changes in stress drive trasnformational changes in the wall of the blood vessel to normalize wall stress
37
angiogenic steps from preexisting vessels again:
1) vasodialate (NO)]] and increase permeability (VEGF)
2) Degrade basal lamina with MMP and disrupt intercellular junctions with plasmalogen activator
3) ANG-2 destabilized vessel
4) Migration and proliferation of endothelial cells with (to) VEGF and FGF
5) Formation of endothelial capillary tube
6) Reform basal lamina with TGF-Beta and recruit periendothelial cells (pericytes or SMCs) with ANG-1-TIE-2 and PDGF
38
high flow on vascular remodeling=
increase in outside diameter and in increase in luminal diameter - vessel wall thickness the SAME
39
low flow on vascular remodeling=
decrease in outside diameter and a decrease in luminal diameter - vessel wall thickness decreases
40
increased pressure on vascular remodeling of large arteries=
outward hypertrophy - vessels become larger in diameter as wall becmoes thicker (smooth muscle externally - hence outward) - diameter of lumen unchanged
41
increased pressure on vascular remodeling of small arteries=
inward hypertrophy - outside diameter remains the same as wall becomes thicker (adding to INSIDE)- diameter of lumen decreases
42
increased pressure on vascular remodeling of arterioles=
- inward hypertrophy
- Inward (eutrophic) remodeling – wall thickness and wall diameter decrease. Prolonged stimulation by NE + ANG II induces activation of ROS-dependent activation of MMPs.
- Rarefaction (vessels disappear)
43
heart layers
1) Endocardium - inner layer (tunica intima) a. Endothelium (simple squamous epithelium) and basal lamina b. Subendothelial layer c. Myoelastic layer: smooth muscle and elastic and collagen fibers d)Subendocardium; Loose connective tissue; Small blood vessels; Nerve fibers; Purkinje cells or fibers (ventricles only)
2) Myocardium contains three types of cardiocytes (tunica media): a) Contractile b) Myoendocrine-Atrial natriuretic factor; B-type natriuretic factor (ventricles); Diuresis and vasodilation; B-type is elevated in congestive heart failure c) Specialized conductive
3) Epicardium (tunica adventitia)-Mesothelium (simple squamous epithelium) and basal lamina; Subepicardium
44
Cardiac skeleton is made up of
Dense connective tissue where cardiac muscle and valves are anchored
45
three layers of AV valves
1) Atrialis – layer of elastic and collagen tissue subjacent to endothelium of the atrial surface. Helps to contract valve
2) Spongiosa – middle layer of loose CT that serves as a shock absorber
3) Fibrosa – core of denser irregular collagenous tissue for mechanical integrity. Is subjacent to endothelium of ventricular surface
46
three layers of semilunar valves
1) Fibrosa – core of denser irregular collagenous tissue for mechanical integrity. Is subjacent to endothelium of aortic or pulmonic surface
2) Spongiosa – middle layer
3) Ventricularis – layer of elastic and collagen tissue subjacent to endothelium of ventricular surface
47
Myxomatous degeneration of AV valve basically means
floppy valves bc of dermatan sulface deposition
48
Conduction tissue of heart
1) SA node- cells smaller than atrial muscle cells; fewer myofibrils; SA node degenerates with age
2) AV node-similar to SA node
3) AV bundle of his- purkunje cells (fibers); travel into subendocardium; gap junctions; few myofibrils
glycogens; 1-2 nuclei
49
CSCs and ECCs differentiate into
cardiomyocytes, SMCs and endothelial cells
50
hCSCs are able to
replace the myocyte compartment 11 to 15 times.
51
Lymphatic vascular system made up of:
1) lymph capillaries: thin blinded end vessels - single layer endothelial cells - incomplete or absent basal lamina-microfibrils for anchoring - no pericytes - no smooth muscle
2) Lymph vessels: like veins but thinner walls - VALVES
3) lymph ducts (thoracic and R lymphatic): like veins, vasa vasorum, smooth muscle present
52
when does tunica intima thickening occur?
occurs in injury and as a normal consequence of aging
- Recruitment of smooth muscle cells
- Smooth muscle phenotype is proliferative/synthetic hence ECM elements are elaborated
53
modifiable risk factors for atherosclerosis
- Hyperlipidemia and cholesterol guidelines: < 200 mg/dL total; < 130 mg/dL LDL; > 45 mg/dL HDL; Triglycerides < 150 mg/dl
- Hypertension
- Smoking – one or more packs per day increases risk 200%
- Diabetes mellitus
- Incidence of MI is twice as high in diabetics as in nondiabetics, when other factors are equal
- 100-fold increased risk for gangrene of lower limb
- Other factors: Elevated C-reactive protein, a marker of inflammation; Elevated homocysteine (controversy exists)
54
nonmodifiable risk factors for atherosclerosis
- Age. Incidence of MI increases 5-fold between 40 and 60 years of age
- Sex. Men are at greater risk than premenopausal women. After menopause, the incidence in women increase until the risk is equal by the 7th to 8th decade of life.
- Family history
- Genetics. Familial hypercholesterolemia may lead to cholesterol levels of 300 to 500 mg/dL; in rare cases, over 800 mg/dL.
55
key events of atherosclerosis
1) Injury to epithelial cells=dysfunction:More permeable and cannot synthesize adhesion molecules
2) accumulation of lipoproteins (LDL)
* **3) oxydation of LDLby smooth muscle, endothelial cells and macrophages***
4) Adhesion of blood monocytes and otherleukocytes to endothelium - Macrophages with LDL=foam cells
5) platlet adhesion=less NO =>increases adhesion of platelets and leukocytes
6) Growth factors are released by platelets, endothelial cells, and macroph=more smooth muscle cells into endothelial compartment of tunia intima-smooth muscle is from precursors in blood or from media layer migration
7) smooth muscle cells tarnsition from contractile to proliferative synthetic=ECM deposited in subendothelial compartment=thickening of tunica intima
8) accumulation of lipids
56
consequences of atherosclerosis:
- ischemic heart disease=coronary artery narrowing and thrombosis - most=ant IV artery
- cerebral infarts=microscopic changes eosinophilia of neurons (red neurons)- neutrophil infiltration occurs at sites where bv are intact; macroph and reactivegliosis
57
wavefront phenomena of cell death
death occurs in the inner wall of the myocardium (subendomyocardium) and proceeds outward toward the subpericardium
58
myocardial infarct consequences:
- Arrythmias
- Acute rupture of the cardiac wall or IV septum
- Rupture of papillary muscles
- Ventricular aneurysm
59
predominant cell type in atherosclerosis
foam cells - macrophages
60
atherosclerosis is (basic)
chronic inflamatory state due to endothelial injury
61
primary lymphatics tissues
bone marrow-make immunocompetent cells
| thymus
62
secondary lymphatic tissues
- lymph nodes - FILTER LYMPH
- mucosa associated lymphatic tissue(SURVEILLANCE-MALT): GUT, BRONCHUS, GU, TONSILS
- spleen-BLOOD FILTER
63
Diffuse Lymphatic tissue (MALT)
- simple organization: part of lamina propria wall of GI tract (GALT), respiratory tract (BALT), GU tract.
- reticular fibers=support framework
- cells: lymphocytes, monocytes, macrophages, and plasma cells
64
lymphatic nodules (follicles)
- non-encapsulated, spherical, dense aggregations of lymphoctes
- primary nodule: homogeneous and small lymphocytes
- secondary nodule: -corona (mantle) zone:outer, dark staining=mature (small) lymphocytes; geerminal center: inner, light staining zone=mature (med&large) lympocytes.
- encounter with antigen=germinal center swells
65
solitary lmphatic nodules are
temporary and can appear or disappear at a particular site
66
Lymphatic aggregates are
permanent
such as: -peyer's batches (B and T lymphocytes-permanent aggregations of lymph nodules in ileum)
-lymph in appendix(in lamina propria and submucosa of appendix)
-BALT(like peyers but in wall of bronchus)
-Lymph noduels in tonsils, lymph nodes, and spleen
67
permanent ymph nodule areas:
tonsils, lymph nodes, and spleen
68
tonsils (3)
- pharyngeal, palatine, and lingual = lymphatic nodules
- form ring around the entrance to oropharynx
- partial/incomplete CT capsule which has septa snet toward interior
- B-lymphocytes
69
pharyngeal tonsils
- adenoid
- nasopharynx
- pseudostrat columnar epith with cilia
- no crypts... has pleats
70
palatine tonsils
- piar... one in each lateral wall bw palatoglossal and pallatopharyngeal arches
- strat squamous non kerat epith
- b-lymphocytes
- epithelial-lined pits=crypts (fssues)= divide tonsil
- multiple lymphatic nodules that produce b-lymph at germinal centers
71
lingual tonils
- small bumps on dorsal surface of post 1/3 tongue
- strat squamous nonkeratinized epith
- crypts
72
lymph nodes
filter lymph before putting it into blood vascular system
73
components of lymph system
- capsule- dense CT; trabeculae (CT septa that extend into lymph node with BV and nerves)
- hilum-concave- where artery and vein leave node with lymphatic vessel
- sinuses-subcapsular: Deep to CT drains into trabecular sinus; trabecular sinuses: separate lymphatic nodules from trabeculae, drain into medullary sinus, endothelial lining(allow cells to pass through), reticular cell meshwork(NOT HOLLOW); medullary sinuses: wide and tortuous, all lined by macrophages
74
flow of lymph:
```
afferent
subcapsular sinus
trabecular sinuses
medullary sinuses
efferent lymphatic vessels (hilum WITH VALVES)
```
75
reticula rtissue
- reticular cells and fibers = 3D meshwork- suspends cells, sinuses and supports lymph node contents
- reticular cells - like fibroblasts... make type III
- dendritic cells- ag-presenting cells that monitor foreign substances
- macrophaes - phagocytotic and ag-presenting
- follicular dendritic cells - bind ag-ab complexes
76
parenchyma (cellular) parts:
cortex -lymphatic nodules
paracortex (deep cortex)
medulla- medullary cords,
77
cortex of lymph node parenchyma
-- lyphatic nodule:
contains b lymphocytes
germinal centers contain dendritic reticular cells - bind newly synthesized immunoglobulin and when these cells reendcounter the same antigen they bind it and present it to the B- and T-lymphocytes.
-more cells than medulla
78
paracortex oflymph node parenchyma
DEEP cortex- no nodules of it's own
contiains t-lymphocytes
-thymus dependent cortex
-postcapillary venules (PVCs)= high endothelial venules (HEVs)--> simple cuboidal to columnar epithelium
-B and t-lymphocy are circulating and enter throughte HEVs (90% of lymphocytes enter via HEVs of paracortex
79
where do B-lymphocytes go?
CORTEX
80
where to t-lymphocytes go?
stay in PARACORTEX
81
medulla of lymph node parenchyma
medullary cords: cellular, reticular cells and fibers
| most b-lymphocytes, plasma cells, dendritic cells, and macrophages
82
blood supply route
Arterial supply → hilum → CT trabeculae → medulla → loose their CT sheath and pass into the medullary cords → form capillary beds. Small branches of the arteries proceed through the medullary cords to the cortex where they form a capillary bed which empties into postcapillary venules. They in turn empty into larger veins → exit lymph node at the hilum
83
thymus
2- lobes
| site of t-lymphocyte maturation
84
parts of the thymus
capsule - t-lymphocyt maturation
cortex
medulla
85
capsule of thymus
- Dense irregular collagenous CT
- Trabeculae partition thymus, to form thymic lobules which are incompletely separated. Each lobule consists of cortex and medulla
- The capsule and trabeculae contain blood vessels, efferent lymphatic vessels and nerve fibers. The CT of the thymus contains collagen, fibroblasts, plasma cells, granulocytes, lymphocytes, mast cells, adipose cells and macrophages
- The medulla of one lobule is continuous with the medulla of other surrounding lobules, since the septa cut through the lobule only part way
- Is the site where T-lymphocytes mature
86
cortex of thymus
- Epithelioreticular cells – form a framework that supports the T lymphocytes
- Type I epithelioreticular cells
- Type II epithelioreticular cells
- Type III epithelioreticular cells
- Note that all 3 types of epithelioreticular cells "protect", "guard", and aim at creating a pristine (antigen-free) environment for the maturing thymocytes residing in the cortex. The cortex is like a school with many students (T-lymphocytes) under training to become immunocompetent. Macrophages residing in the cortex phagocytize T cells that do not meet thymic education requirements
- Small T-lymphocytes (thymocytes): Undergo a progressive maturation and differentiation as they move from the cortex toward the medulla; 98% of mature T-lymphocytes die (undergo apoptosis) in the cortex and are eliminated by local macrophages; Surviving mature T-lymphocytes migrate to the medulla and then leave the medulla ("graduate") via the vascular system to be delivered to secondary lymphatic organs (that is, the thymus-dependent zone of lymph nodes known as the paracortex and the PALS of the spleen)
87
medulla of thymus
- Type IV epithelioreticular cells are associated with Type III cells and participate in the establishment of a "barrier" at the corticomedullary junction
- Type V epithelioreticular cells form the meshwork / cytoreticulum (framework) of the medulla
- Type VI epithelioreticular cells form thymic corpuscles called Hassall's corpuscles - concentric, eosinophilic, whorls, unique to the thymic medulla. They exhibit keratinization
- Lighter-staining and less cells than cortex
- Contains mature T-lymphocytes
- Immunocompetent cells leave thymus, enter the blood stream from the medulla via postcapillary venules to take up residence in the paracortex of the lymph nodes and PALS of spleen
88
blood thymus barrier consists of:
- Endothelium
- Basal lamina
- Macrophages
- Type I epithelioreticular cells
89
vascular supply of thymus
arteries-->capsule--->bw lobules via trabeculae--->corticomedullary junction--->form capillary beds ---> cortex
90
cortical capillaries of thymus:
continuous type-thick basal lamina covered by sleeve of type I epithelioreticular cells (=thymus blood barrier)
91
Di Georges syndrome
cant produce T-plymph
death from infection.
thymus has n oafferent lymphatic vessels
92
Spleen
largest lymphatic organ
| inspectsblood cells - filters blood
93
capsule of spleen
covered by mesothelium: Dense irregular collagenous CT. Also contains smooth muscle cells and elastic fibers; Trabeculae (septa) carry branches of the splenic artery deep into the spleen
-Site of B- and T-lymphocyte proliferation
94
hilum of spleen
blood vessels and nerves enter and leave organ
95
CT stroma of spleen
reticular fiber 3D meshwork
96
vascular supply to spleen:
-splenic artery enters at hilum-->trabeular arteries---->central artery or periarterial lymphatic sheath(PALS-tunica adventitia infiltrated with T-lyphocytes)--->penicillar arterioles (when looses lymphatic sheath)--->arterial capillaries/sheathed capillaries (with macrophage sheath)---> empty into splenic cords--->splenic sinuses--> general circulation
97
circulation of the spleen is:
OPEN- arterial capillaries end near the sinusoids, and blood from these capillaries seeps into the splenic cords (red pulp) and then into the splenic sinusoids
98
white pulp of spleen
- parenchyma -
- blue with hematoxylin)
- PALS:Is the thymus-dependent zone of the splenic pulp; Contains T-lymphocytes; Central artery is centrally-located within the PALS and that is why it is called the “central artery”
- Splenic Nodules (Malpighian Corpuscles): Are lymphatic nodules; Contain B-lymphocytes; May contain a germinal center around the central artery; Central artery is eccentrically-located in the lymphatic nodule
99
marginal zone of spleen
parenchyma
| bw red and white pulp
100
red pulp of spleen
parenchyma
- Are irregular and branching cords of splenic tissue; Contain a loose network/framework consisting of reticular cells and reticular fibers; Spaces between fibers are filled with blood (RBC’s, granulocytes, lymphocytes, and platelets) that is filtered; Filter blood; Contain macrophages, plasma cells, and dendritic cells
- Splenic Sinuses (Sinusoids): Are lined by endothelial cells, with wide intercellular spaces allowing blood cells to pass in and out of the sinuses; Drain into pulp veins which in turn drain into trabecular veins
101
Type I epithelioreticular cells
Thymus-form a "seal" around the cortex, separating it from the CT capsule and trabeculae. They also form a sleeve around the tunica adventitia of vessels. Type I cellsform occludens junctions sealing the thymic cortex from the rest of the body
102
Type II epithelioreticular cells
(thymus)are branching, stellate-shaped cells that form a meshwork / cytoreticulum in the midcortex. Type II cells are held together by desmosomes. These cells are like "teachers" involved in "thymic cell education"
103
Type III epithelioreticular cells
(thymus) reside in the deep cortex and the corticomedullary junction. Involved in protein synthesis, form occludens junctions. They form a "seal" between the cortex and medulla, isolating the two
104
Type I epithelioreticular cells
Thymus-form a "seal" around the cortex,separating it from the CT capsule and trabeculae. They also form a sleeve around the tunica adventitia of vessels. Type I cellsform occludens junctions sealing the thymic cortex from the rest of the body
105
Type II epithelioreticular cells
(thymus)are branching, stellate-shaped cells that form a meshwork / cytoreticulum in the midcortex. Type II cells are held together by desmosomes. These cells are like "teachers" involved in "thymic cell education"
106
Type III epithelioreticular cells
(thymus) reside in the deep cortex and the corticomedullary junction. Involved in protein synthesis, form occludens junctions. They form a "seal" between the cortex and medulla, isolating the two
107
where do b-lymphocytes originate?
bone marrow
108
where do t-lymphocytes originate?
begin in bone marrow and move to thymus to mature
109
hypothalamus consists of two populations of cells and does what:
- central role in the coordination of endocrine functions and the integration of endocrine and autonomic functions.
- controls the pituitary gland
1) neurons that produce and release neurotransmitters, and 2) special neurons that produce and release hypothalamic neurosecretory hormones, instead of neurotransmitters.
110
hypothalamus regulates the activity of with neurotransmitters and hypothalamic neurosecretory hormones?
pituitary gland - the master endocrine gland
anterior lobe=glandular
posterior lobe=neural
111
hypothalamic neurosecretory hormones (Releasing or inhibiting hormones-Factors)
- synthesized in neurons of the hypothalamus
- released by axon terminals into the primary capillary plexus (fenestrated capillaries in the median eminence)
- then drain into the hypophyseal portal veins (located in the infundibulum)
- then pass into second capillary plexus (the sinusoidal cap with fenestrated endothelium in ant pituitary
- releasing or inhibiting hormones pass into the parenchyma of the ant lobe of pitutary to influence secretory cells there
112
Growth Hormone-Releasing Hormone (GHRH)
stimulates the secretion of somatotropin (growth hormone, GH)
113
Prolactin-Releasing Hormone (PRH
stimulates the secretion of prolactin
114
Prolactin-Inhibitory Factor (PIF)
inhibits the secretion of prolactin
115
Corticotropin-Releasing Hormone (CRH)
stimulates the secretion of adrenocorticotropin (ACTH)
116
Thyroid-Stimulating Hormone-Releasing Hormone (TSH-RH) (also known as Thyrotropin-Releasing Hormone [TRH])
stimulates the secretion of thyroid stimulating hormone (TSH)
117
Gonadotropin-Releasing Hormone (GnRH)
- stimulates the secretion of Luteinizing Hormone (LH)
| - stimulates the secretion of Follicle Stimulating Hormone (FSH)
118
Supraoptic and paraventricular nuclei of the hypothalamus
- House the cell bodies of neurosecretory cells
- synthesize vasopressin (antidiuretic hormone, ADH) and oxytocin. Cells also synthesize neurophysin (a carrier protein) which binds to the above 2 hormones
- Their neurosecretory cells give rise to unmyelinated axons which form the hypothalamohypophyseal tract. This tract, carrying the above hormones (bound to neurophysin), descends to terminate near the capillaries in the posterior lobe of the pituitary gland. There, the axon terminals release the hypothalamic hormones (ADH and oxytocin) which then pass into the capillaries.
119
Adenohypophysis (Anterior Pituitary)
- Also referred to as the Pars Distalis (Pars Anterior, Anterior Lobe)
- is covered by a fibrous CT capsule
- consists of cords of cells (glandular epithelial tissue)
- contains reticular fibers
- contains fenestrated sinusoidal capillaries (of secondary capillary plexus): fenestrated endothelial lining-permits the diffusion of releasing factors into gland-permits gland secretory products to pass into capillaries
- Chromophils and chromophobes
120
Chromophils
- cell of ant pituitary (“color friendly”) contain secretory granules that have an affinity for dyes)
- ---->Acidophils:stain orange-red with acidic dyes; are the most common cells of the pars distalis -types: 1) somatotropes-- are stimulated by GHRH-- are inhibited by somatostatin-- secrete somatotropin (GH) which increases cellular metabolic rates, --influences long bone growth (growth plates) --excessive GH causes gigantism in children and acromegaly in adults
2) lactotropes (mammotropes)-- stimulated by PRH -- inhibited by PIF-- produce prolactin which promotes mammary gland growth during pregnancy & lactation following birth
- --->Basophils: stain blue with basic dyes (PAS) -types: 1) corticotropes-- stimulated by CRH-- secrete ACTH which stimulates the adrenal cortex to produce cortisol and corticosterol
2) thyrotropes-- stimulated by TRH-- secrete TSH (thyrotropin)-- inhibited by T3 and T4 in the blood
3) gonadotropes-- stimulated by GnRH-- secrete FSH and LH-- function in male and female reproduction
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Chromophobes
- cell of ant pituitary- color fearing - no affinity for dyes
- may be degranulated chromophils
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Pars intermedia (zona intermedia)
- ant pituitary part
- contains Rathke's cysts containing colloid (function unknown). Cysts are remnants of the ectoderm of Rathke's pouch. They are rudimentary in humans
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Pars tuberalis
- ant pituitary part
- forms a "sleeve" around the hypophyseal stalk
- is very vascular (by arteries and hypophyseal portal system)
- may release ACTH, FSH and LH
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infundibulum
- post pituitary part
| - continuous with the median eminence of the hypothalamus
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pars nervosa
- post pituitary part
- not an endocrine gland - neural secretory tissue
- receives the unmyelinated hypothalamohypophyseal tract terminals (containing ADH and oxytocin), that is, it serves as a storage depot for neurosecretions produced by neurons of the supraoptic and paraventricular nuclei of the hypothalamus
- Herringbodies - cross section of axons/axon terminals
- pituicytes-glia-like, local cells that cover and support axons and their terminals
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herringbodies
- post pituitary - pars nervosa
- are accumulations of neurosecretory granules in the axons and axon terminals of the hypothalamohypophyseal tract
- nervous stimulation causes these granules to release their contents near the fenestrated capillary plexus
- contain either (a or b):
a) vasopressin (ADH) -target: distal tubules and collecting ducts of the kidney (resorb water); function: lowers urine volume
b) oxytocin-target: uterine myometrium, and myoepithelial cells of mammary gland; function: stimulates smooth muscle contraction of uterus (for parturition) and mammary gland (for lactation)
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Pituitary Adenomas
- common, benign tumors of the anterior pituitary
- may affect the secretory activity of other cells in anterior pituitary
- may compress and wear down surrounding neural tissue and bone
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Diabetes Insipidus
- may be caused by damage to the hypothalamus or the pars nervosa
- results in reduction of ADH
- insufficient water resorption by the kidney
- polyurea (excess urination) and dehydration
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Arterial Supply to pituitary
Internal carotid artery branches:
1) superior hypophyseal arteries
- supply pars tuberalis
- supply infundibulum
- form the primary capillary plexus in the median eminence
2) inferior hypophyseal arteries
- supply posterior lobe (mainly)
- note that the anterior lobe does not have its own blood vessels
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Venous Drainage of pituitary
primary capillary plexus (of the median eminence) empties into → hypophyseal portal veins (in the infundibulum) which empty into → secondary capillary plexus (of the anterior pituitary) → cavernous sinus → systemic circulation
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thyroid gland capsule
- derived from the deep cervical fascia
- dense irregular collagenous connective tissue
- gives rise to trabeculae that partition the gland into lobules: trabeculae carry blood vessels, lymphatic vessels, and nerve fibers deep into gland. Thyroid gland is an endocrine gland and is very vascular; parathyroid glands are located within the capsule covering the posterior part / surface of the thyroid gland
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thyroid gland function
-synthesizes the following hormones:
a. T3 (triiodothyronine)
b. T4 (tetraiodothyronine, thyroxine)
(a,b) -These hormones regulate cell and tissue metabolism and heat production
c. calcitonin (thyrocalcitonin)- Is involved in the regulation of blood calcium levels
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thyroid follicle
-is the basic structural and functional unit of the thyroid
-spherical, variable diameter
-surrounded by a basal lamina, reticular fibers, and then a fenestrated capillary plexus
-store glandular secretory product in follicular lumen (extracellularly)
note: in contrast, other endocrine glands accumulate their secretory product(s) in the parenchyma (cellular part of gland), that is, the
secretory product is stored within the secretory cells
-follicular epithelium (follicular cells, principal cells)
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follicular epithelium of thyroid
i. simple squamous – low level of activity
ii. simple cuboidal – normal level of activity
iii. simple columnar – highly active
iv. Organelles: The nucleus is round to ovoid. The cytoplasm is basophilic (due to ribosomes on RER). RER are the site of
protein synthesis and glycosylation. Golgi apparatus is site of glycosylation and packaging of secretory product. The vesicles contain thyroglobulin. The lysosomes contain proteases. The microvilli ↑ absorption.
v. The luminal surface of the cell membrane faces and comes in contact with the colloid
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parafollicular cells of thyroid
-clear cells, c-cells
i. are derived from the neural crest
ii. are wedged between follicles (are not exposed to colloid), lie within basal lamina surrounding follicles, and are near many
capillaries
iii. are light-staining, with a round nucleus
iv. their dense secretory granules contain
a) calcitonin (thyrocalcitonin)
i) is a peptide hormone
ii) is released by parafollicular cells when
blood calcium levels are high -Calcitonin lowers blood calcium levels to NORMAL as follows: It inhibits bone breakdown by osteoclasts; It promotes calcium deposition in bones (osteoid calcification)
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lumen of thyroid
i. colloid
a) thyroglobulin (glycoprotein)
b) hormones (bound to thyroglobulin)
i) T3
ii) T4
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synthesis of thyroid hormones is controlled by
TSH and iodide levels
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synthesis of thyroid hormones
1) basophils (thyrotropes secrete TSH
2) TSH goes to thyroid gland and binds TSH receptor on follicular cells
3) follicular cells make thyroglobulin (in RER) and also glycosylation in golgi
4) Golgi form vessicles and secrete (exocytosis) into follicular lumen - has tyrosine residues
5) iodine enters body via diet and is reduced to enter bloodstream
6) iodide in bloodstream pumped into follicular cells (active transport - NA/I symport)
7) oxidized into active iodine with thyroid peroxidase (membrane bound) with H2O2
8) iodine iodinates the tyr of each thyroglobulin moleule to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) via thyroid peroxidase
9) MIT + DIT = triiiodinated tyrosine & DIT + DIT=tetraiodinated tyrosine
-throglobulin is not hormone - INACTIVE STORAGE FORM OF THYORID HORMONES
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basophils -(thyrotropes) secrete
thyroid stimulating hormone (TSH)
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T3 is mostly produced by
conversion from T4 by heart, liver and kidney
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release of thyroid hormones T3 and T4
1) ant pituitary gland basophils (thyrotropes) release TSH
2) TSH enters blood and goes to thyr gland
3) TSH binds follicular cell basal membrane
4) filopodia form at luminal surface of follicular cells
5) endocytosis (cell eating) of colloid
6) vesicles enclosing colloid unite with endosomes – in cytoplasm
7) endosomes contain proteases which split the iodinated tyrosine residues from the thyroglobulin
8) iodinated tyrosine residues are released into the cytoplasm as: uncoupled monoiodotyrosine (MIT), uncoupled diiodotyrosine (DIT), and T3 and T4 that formed earlier during coupling reactions of MIT + DIT and DIT + DIT, respectively.
9) iodotyrosine dehalogenase splits iodine from the free monoiodotyrosine MIT and diiodotyrosine (DIT)
10) iodine and tyrosine remain in cytoplasm for recycling
11) T3 and T4 liberated from follicular cell basement membrane -- to capillaries
12) thyroglobulin breakdown by lysosomal proteases and carbs
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T4 is only produced by:
throid follicular cells
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T3 is mostly produced by
conversion from T4 by heart, liver and kidney
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T3/T4 effect on body:
- ↑ cellular metabolism
- ↑ growth rate
- ↑ mental activity
- stimulation of endocrine gland function(s)
- stimulation of carbohydrate metabolism
- ↓ formation of phospholipids, and triglycerides, enhance the production of endogenous cholesterol
- ↑ formation of fatty acids
- ↑ of thyroid hormone synthesis results in: ↓ body weight; ↑ in heart rate, metabolism, respiration, muscle function, and appetite.
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parathyroid glands histology
1. Covered by a collagenous connective tissue capsule which sends septa that
2. carry blood vessels, lymphatic vessels, and nerve fibers into the glands
3. Septa and reticular fibers form a supporting framework
4. Fenestrated capillary network
5. In the adult, adipose tissue is present (makes up about 60-70% of gland)
6. Parenchyma contains epithelial cells arranged as cords or clusters
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chief cells (parathyroid)
- eosinophilic
- secretory granules =parathyroid hormone (PTH)
- ribosomes on rER manufacture preproparathyroid hormone
- splits into proparathyroid hormone and polypepdide while moving around in rER
- when moved to Golgi splits into parathyroid hormone and another polypeptide
- put into secretory vessicle and exocytosed
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oxyphil cells (parathyroid)
- function unknown but may be dormant-inactive chief cells
- intensely eosinophilic (due to mitochondria)
- larger than chief cells - are dispersed throughout the gland as single cells, or cluster
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intermediate cell (parathyroid)
No body knows what this guy does.
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effects of PTH
- regulates CA and PO4 levels (inc CA and dec PO4)
- low CA stimulates release of PTH/high levels inhibit
- PTH(inc CA) and calcitonin(dec CA) have reciprocal effects
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PTH on Bone
- PTH attaches to osteoblast receptors
- causes osteoblasts to release osteoclast-stimulating factor, which triggers osteoclast activity (bone breakdown = osteolysis), freeing calcium from bone to enter the bloodstream
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PTH on kidney
- PTH prevents calcium loss in the urine
| - PTH promotes phosphate loss in the urine
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PTH on GI tract
- PTH increases low calcium levels in the blood to normal
- calcitonin decreases elevated calcium levels in the blood to normal
- cotnrols formation of Vit D in the kidneys --> vit D related to CA absorption
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removal of parathyroid glands:
will drop blood CA levels = tetanic contraction of muscles (ncluding laryngeal and respiratory = death
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pancreas
-Covered by a connective tissue capsule
-The capsule gives rise to septa that: Partition the gland into poorly-defined lobules; Carry blood vessels, lymphatic vessels, nerves and gland ducts
-Consists of exocrine and endocrine portions which produce digestive
enzymes and hormones, respectively
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endocrine pancreas cells
i. Alpha cells:Glucagon: Affects liver, skeletal muscle and adipose tissue; Increases blood glucose levels PINK
ii. Beta cells: Insulin: Decreases blood glucose levels BLUE
iii. Delta cells: Somatostatin: Reduces smooth muscle contraction of digestive tract and gallbladder
iv. G cells: Gastrin; Stimulates synthesis of HCl by parietal cells
in the stomach mucosa
v. PP cells (F cells): Pancreatic polypeptide; Inhibits pancreatic exocrine secretions
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Diabetes Mellitus
1) Type 1 diabetes (insulin-dependent, juvenile-onset diabetes): Affects individuals under 20 years of age--> Signs: Polydipsia (excessive thirst); Polyphagia (excessive eating); Polyuria (excessive urination)
2) Type 2 diabetes (non-insulin-dependent diabetes): Most common; Affects individuals over 40 years of age
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anatomy of suprarenal (adrenal) glands
1. Connective tissue capsule: CT trabeculae carry blood vessels and nerve fibers deep into the gland
2. Parenchyma: -->Cortex (outer region)- Makes up about 90% of organ; Produces corticosteroids
- -> medulla (inner region): Functionally associated with the sympathetic nervous system; Produces catecholamines (epinephrine and norepinephrine)
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zona glomerulosa of adrenal gland
-cortex
-(outer zone) (L. glomerulus, "ball of yarn")
-->Columnar cells arranged in cords and clusters
-->Acidophilic cytoplasm; Abundant SER, mitochondria, GA, RER, lipid droplets, free ribosomes
-->cells synthesize mineralocorticoid hormones- Aldosterone (mainly): Main target: distal convoluted tubule of the kidney; Function: stimulate water balance, absorption of
sodium and excretion of potassium
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zona fasciculataof adrenal gland
- cortex part
- intermediate zone
- Largest layer
- Sinusoidal capillaries
- Cells (spongiocytes) are arranged in radial columns with sinusoidal capillaries running in between
- Have lipid droplets, after tissue processing lipid vacuoles impart a "foamy" appearance and cells are referred to as "spongiocytes"
- Abundant SER, GA, mitochondria, lipofuscin pigment
- Cells synthesize glucocorticoid hormones: Hydrocortisol (cortisol); Corticosterone; Function in control of carbohydrate, fat and protein metabolism
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Cushing's Syndrome (Hyperadrenocorticism)
Results from small tumors of the basophils in the anterior pituitary gland. Tumors produce excess ACTH which over stimulates the suprarenal cortex (cortex enlarges) and produces excess cortisol. Affected individuals become obese, mainly in the face, neck and trunk. Impotency in males, amenorrhea in females
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zona reticular of adrenal gland
- cortex
- inner zone
- Intensely acidophilic, cells contain lipofuscin pigment
- Cells form anastomosing cords
- Cells synthesize ("weak") androgens: Dehydroepiandrosterone; Androstenedione
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Suprarenal Medulla
- Is derived from neural crest cells
| - Is a "modified sympathetic ganglion"
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cells of suprarenal medulla
- -->Chromaffin cells
- Are modified neurons - no dendrites or axons
- Form cords or clusters
- Synthesize catecholamines (neurotransmitters) which are released by 2 different populations of cells: Epinephrine; Norepinephrine
- Catecholamines prepare the body for the “fight-or-flight” response; Receive the axon terminals of preganglionic sympathetic neurons of splanchnic nerves which release Ach; are equivalent to postganglionic sympathetic cells (but no dendrites or axons)
- ->Sympathetic ganglion cells: in CT of medulla; send their axons to the cortex where they modulate cortical activity and innervate blood vessels
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very high levels of thyroid hormone results in
- muscle tremor, fatigue, impotence in men, and abnormal menstrual bleeding in women
