histology - block 3 Flashcards
3 kinds of arteries
elastic - conducting veseels - aorta - main branches
muscular - main distribution
arterioles - terminal branches
as vessels decrease in size, elastic decreases and smooth muscle has more prominence
3 layers of wall
tunica intima, media, adventintia
tunica intima?
- endothelium and basal lamina
- subendothelium (very think loose CT - may have smooth muscle fibers
collagen and smooth longitudinally
- internal elastic membrane (optional
tunica media?
- concentric layers of helically arranged smooth muscle
- between muscle fibers - elastic and lamellae, collagen and proteoglycans - SYNTHESIZED by smooth muscle
- thin external elastic lamina - - found in larger arteries
tunica adventitia?
Loost CT - longitudinall collagenous and elastic fibers -
collagen type 1 merges w/ surrounding tissue
VASO VASORUM,
small vessels in adventitia and outer media of larger vessle -
nourish to thick layers - more frequent in veins
innervation?
sympathetic - unmylienated - norephinephrine - vasoconstriction
arteries in skeletal also receive cholingergic nerve supply
smooth muscle relax (vasodilate when sympathetic stim decreases or when NO, K+, N+, or lactic acid are present
What can cause vasodilation?
smooth muscle relax (vasodilate) when sympathetic stim decreases or when NO, K+, N+, or lactic acid are present
Para? arteries in skeletal also receive cholingergic nerve supply
elastic arteries - tunica intima layer?
look yellow in sample,
wall is thinner for size of vessel
- tunica intima thicker
endothel - simple squamous - microvilli, pinocytotic vesicles, RER, microfilaments, Intercellular junctions, Lysosomed
ROD like inclusions - WEIBEL palade bodies - contain factor VIII antigen (von-Willebrand factor), interleukin 0, P selectin, adn endothelin
- Thick subendothelium - collagen and elastic with some smooth muscle
- indistinct internal elastic lamina - (hidden by elastic laminae)
elastic arteries - tunica media
> 40 layers of concentric smooth muscle fibers - THICK
elastic laminae secreted by smooth muscle - number and thickness INCREASE with AGE and HYPERtension
collagen fibers and proteoglycans, mainly chondrolitin sulfate - between layers
NO distrinct external elast
elastic arteries - tunica adventitia?
smaller than media in thickness
Loose CT, fibroblasta dn collagen bundles longitudinally - some elastic
Can elastic arteries actually propel the blood?
Yes - the store mechanical energy for short time - smooth muscles with high elastic wall stretch
elastin recoils and propels blood when ventricles relax
blood is ejected from heart into elastic arteries, walls strech - accommodating surge - by stretch the elastic sheet and fibers store energy - and function as pressure reservoir.
elastin recoils - stored energy is used to propels blood -
Muscular arteries?
distributing arteries - medium sized -
TUNICA INTIMA
endo + basal
subendo (delicate elastic and collagen fibers, few fibroblasts, some smooth muscle)
internal elastic lamina prominent - thick fenestrated band - junctions with smooth muscle cells of mediat
TUNICA MEDIA
4 - 40 layers of circular smooth - they regulated diameter of lumen and at injury site may close to reduce hemorrhage
elastic and reticular fibers
EXTERNAL elastic lamina - with nerve axons and elastin
TUNICA ADVENTITIA -
loose CT, fibrobalasts, elastic fibers, collagen - longitudinally - lympathtics, vasa vaorum, nerve and adipose
merges with surrounding CT
what happens when an artery is injured?
VASCULAR SPASM
small artery can close - smooth muscle contracts in a vascular spasm - shutting down blood flow
arterioles?
principle blood flow regulator -
tunica intima -
endo on thin basal lamina
very thin subendothelial CT -
Internal elastic thin and fenestrated - absent from terminal arterioles
TUNICA MEDIA
1 - 5 layers of smooth muscle with some elastic - no definite external elastic layer
TUNICA ADVENTITIA - thinner than media - loos, longitudianlly oriented collagen and elastic fibers
Carotid bodies? where are they?
near bifucation of common carotid
What do carotid bodies do?
chemoreceptor sensitive to low oxygen tension high carbon dioxide , and low PH of arterial blood
what are carotid bodies made of? SENSORY organs of arteries
glomuc cells - type 1, and sheath cells or sustentacular Typpe OO cells with rich vascular supply - capillaries fenestrated - many nerves throughout.
What are aortic and jugular glomeruli?
similar in structure to carotid bodies ??
Carotid body? and cartodi sinus?
catotid body - at bifucation, chemoreceptor for Oxy level -
visceral sensory - glossopharyngeal - CN IX, some via vagus CN X
cartoid sinus
prosimal internal carotid
barorecpetor -
same nerves as above
carotid sinus
stim by STRETCH
appears as dilation of lower end of internal cartodi - baroreceptor
tunica media thinner, adventitia thicker - w/ larger no. of senosry nerve ending with glossopharyngeal nerve - stimulated by STRETCH
reaccts to change in blood pressure - and inittiated reflexes tha modigy pressure
age changes in artieres?
tunica intima -
more connective tissue fiber and proteoglycans - become thicker
smooth muscle appear and synthesize collagen and elastic fibers -
vessels become MORE RIGID
ELASTIC arteries - lay down more elasti lamellae
MUSCULAR - increase in muscle w/0 elastic fibers - advanced age - loss of elastic tissue mades vessels elongate and become tortuous
clinical disorders?
aneurysm?
TYPE IV Ehler’s Danlos
translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial
Marfans
The most dangerous complications of Marfan syndrome involve the heart and blood vessels. Faulty connective tissue can weaken the aorta — the large artery that arises from the heart and supplies blood to the body. Aortic aneurysm.
the fibers that support and anchor your organs and other structures in your body. Marfan syndrome most commonly affects the heart, eyes, blood vessels and skeleton
media weakened by embryonic defect, deisea or lesion - wall of artery dilates and may rupture
TYPE IV Ehler’s Danlos
Marfans (autosomal dominant - asso w/ aortic dissecting
Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or back pain, often described as “tearing” in character.
arteriosclerosi?
thickening of walls, loss of elasticity
Atherosclerosis - fibrofatty plagues in intima
Calcification of tunica media
calcium deposit in media
arteriolosclerosis?
thickening of walls of smaller arteris
formation of atherosclerotic plaque?
When plaque (fatty deposits) clogs your arteries, that’s called atherosclerosis. These deposits are made up of cholesterol, fatty substances, cellular waste products, calcium and fibrin (a clotting material in the blood). As plaque builds up, the wall of the blood vessel thickens.
1.increased permeability to LDL cholesterol.
2 endothelial injury increase ROS - which oxidized LDL in tunica intima
3 endothelial cell express cell adhesion molecules CAMS - that intiiate monocyte migration that differentiate in to macrophages
4 Macrophages phagocytize oxidized LDL - become FOAM cells - with spongy appearance loaded with lipid containing vesicles
- platelet derived growth factor PDGF and other growth factors stimulate migration of smooth from media to intima
- in intima, smooth produce lots of ECM increases thicken of Intime
What are FOAM cells?
macrophages or smooth muscle full of lipid material
BLOCKS lumen?
angioplasty - mechanical widening of narrowed/ obstructed arteries
What happens when you eat a cheeseburger?
LIPASE from saliva - breaks into free fatty acids, monoglicerides, cholesterol.
Lipase also comes from pancreas - will be used in small intestine fat breakdown
Path past stomach of cheeseburger?
small intestines, packaged into big fat globules, Liver releases bile which acts on globules, breaking them into smaller droplets
GOAL - adequate surface area
What acts first on fat? bile salts or pancreatic lipase?
Bile salts break down into small droplets - then pancreas lipase
If bile salt step doesn’t happen, trouble - because pancreatic lipase is not as effective
What does pancreatic lipase do to reduced (via bile) fat droplets?
MICELLE _ package
This is what can enter enterocyte - releasing free fatty acid, monoglycerides, cholesterol.
didn’t salivary lipase already do this? It couldn’t do it all -
MUCH stronger! so strong - would hurt your mouth
Micelles are essentially small aggregates (4-8 nm in diameter) of mixed lipids and bile acids suspended within the ingesta. As the ingesta is mixed, micelles bump into the brush border of small intestinal enterocytes, and the lipids, including monoglyceride and fatty acids, are taken up into the epithelial cells.
In enterocyte, what do free fatty acid, monogliceride, and cholesterol form?
TRIglycerides form CHYLOMICRONS (also fat soluble vitamins)
Where does chylomicron go from small intestine?
LYMPH - apo48 (bombs) drops chylomicrons from GI into Lymphatic system
apob48 DROPS these bombs from GI to LYMPH system
once in lymph, where go?
blood system -
differences between HDL (good) and LDL (bad)
high density vs low.
Why is HDL good?
puts more APO proteins on chylomicron - which helps processing - HDLs carry APO proteins around - and drop them off -
Donates - APOC2 and APOE
Now chylo - has THREE APOS on its surface.
apo48, APOC2, and APOE
APOC2? APOE?
APOc2 - activates LPL -
LPL hydrolyze - cuts triglicerideas into fatty acids to be absorbed by body
APOc2 - CUTS and CLEAVES
(insulin also activates LPLs) causing weight loss Type 1 diabetes
APOe?
super important in pathway -
everything has to be broken down into remnants -
APOE gatekeeper - lets remnants be recycles -
APOE EATS the remnants - recycles,
where does the smaller chylomicron remnant go?
to the liver - where it is allowed in.
what secretes VLDL? what does it have inside?
liver -
triglycerides and cholesterol inside
with apoB100 on shell.
what does HDL do to VLDL?
HDL - good fat -
loads VLDL - giving away APOc2 and APOE
Role of apoc2?
activate LDL to hydrolize and convert triglycerideas into fatty acids for absorption.
once apoc2 reacts on vldl?
changes to IDL - intermediate density - on its shell is APOE and APOB100
can ENTER liver and there be converted to LDL
What doesn’t enter liver is converted into LDL also (still has APOB100)
peripheral cells and LDL getting in?
needs APOB100 - that’s the receptor key
why is LDL bad?
because it takes triglycerides and ? and takes them from the liver where they are stored and puts them into peripheral cells - using the APOB100 key to get inside.
which can cause disease
High YIELD - if see APOB100
APO B100 makes you fat - makes you gain 100 pounds.
know that this will allow fat, cholesterol, etc LDL entry into peripheral cells. endocytosis
APO B100 makes you fat - makes you gain 100 pounds.
why is HDL the good one?
donates APO#, APOC2 - allowing reuptake and cleaver triglycerides into fatty acids for absorption.
where does HDL come from?
secreted from liver and small intestine - baby HDL - nascent
What converts nascent HDL to mature HDL?
Lcat - activated by APOA1 -
What would happen if no APOA1?
this allows creation of HDL - APOA1 -
Activates Awesome fat!
How does body make Vitamin D?
skin uses sun and cholesterol.
What parts of body use cholesterol in hormones?
testosterone, adrenal glands.
How does liver use cholesterol?
Makes bile acids to digest food.
Where do triglycerides come from?
food and liver -
Does body need triglycerideas?
yes, uses fat as energy. But fat can’t be directly put in blood stream, needs to be packaged. Lipoprotein - then can move through body to cells that need it.
Cholesterol can be packaged differently - and depending upon that?
things are better or worse. liver makes VLDL (very low density) which makes LDL - Bad. VLDLs are stuffed with cholesterol and triglycerides
Does VLDL travel through your bloodstream?
Yes, and they provide energy to your cells.
What if body makes more VLDL than you need?
Stores the extra triglycerides as body fat. When gives up the triglyceride - becomes LDL the LDLs then travel thru blood providing cholesterol to cells that need it.
What does body do if it has more LDLs than it needs?
Builds up depositing plaque in blood vessels. If vessel walls are damaged, it is easier for plaque to form. Over time, builds up, narrows vessels. Hence BAD LDLs
Where do LDLs often form plaque?
in coronary arteries, carotid (increasing stroke risk bec lack of blood to brain).
What are HDLs?
Liver also makes these - GOOD - inside they have less triglyc and cholesterol than LDL.
What good things does HDL do?
Helps remove cholesterol from cells and from plaque in vessels.
What does HDL do with cholesterol it picks Up?
Takes to liver - which then removes excess cholesterol via bile ?
Cholesterol appropriate levels?
Cholesterol <200mg/dL
HDL>60 or higher
LDL < 100
Triglyc > 150
Saturated vs. Unsat fats?
Saturated / Trans - raise LDL - (solid at room temp)
Meds to reduce cholesterol?
Statins - reduce cholesterol made in liver - effect LDLs mostly
Niacin - reduces LDLs and triglyc and increases HDL made in liver
Bile Acid binding drugs - prevent reuse of bile after being used to help digest food - therefore liver uses up MORE cholesterol lost bile.
Fibrates mainly reduce trigly in blood but also raise HDL levels
Cholesterol absorption inhibitors - reduce cholesterol absorbed in intestines
4 types of lipoproteins?
Chylomicron, VLDL, LDL< HDL
HDL has most amount of protein in ratio to lipids
In this order - Lease protein to most
Is cholesterol a protein or a lipid?
a combo - lipoprotein
What do chylomicrons do?
transport and deliver fat to tissues
how are cholymicrons formed?
in small intestine - lipid broken into micelles
Micells in cells then package - with fatty acid, monodlyceroi, adopocytes, and cholesterol in to cholymicrons
Which GO into lymph - and then blood delivering where needed
remnants go to liver - bind on to LDL receptors - brought into liver.
how is cholesterol made? LONG story - but
in liver, from gluose, via mitochondria - pyruvate to acetyl-coa using enzyme HMG - coa reductase
STATINS inhibit HMG - so less cholesterol in created
Can body make HDL?
it just makes the container - EMPTY _ which goes through body collecting cholesterol.
OR it can make VLDLs - which main job is to transport triglyc and cholesterol to body.
How does VLDL once in blood stream deal w/ lipase?
Liberated fatty acids in Lipase - VLDL becomes IDL (intermediate DL) - and fatty acids can be stored as fat or used by tissues for energy.
How are LDLs created? What is its job?
IDL converts to LDL - which main job is to transport cholesterol to tissues (it has A LOT of cholesterol)
Why does body need cholesterol?
hormones and cell membrane liquidity, one more??
What happens to LDLs once they deliver cholesterol?
return to liver, bind to LDL receptors - can recycle in to golgi to make more lipoproteins or be excreted
What does empty HDL do?
picks up cholesterol in circulation - full HDL returns to liver binding to scavenger receptors - and takes cholesterol into liver.
Statins? action in hepatocyte
inhibits cholesterol formation in liver.
ALSO
gets rid of LDLs and creates HDL.
bad aspects? toxicity
Myology, rhab…
Niacin? action in hepatocyte and in vessles
in hepatocyte -
inhibits VLDL secreting into blood
inhibits Lipolisis in the vessels?
decreases LDL (as VLDL not around) HDL also increased
What is lypolosis?
the breakdown of fats and other lipids by hydrolysis to release fatty acid in the endothelial cells
Bile acid resins?
stops bile reabsorption when comes back to the liver.
fat soluble Vitamins also not able to get into liver
creates Gallstones
decreases LDL - because using up other cholesterol.
HDL - slight increase
Cholesterol absorption blockers
inhibits reabsorption of cholesterol (as opposed to reabsorption of bile)
decrease LDL
No effect on HDL
Fibrates?
work in vessels - decrease lipilosis - uptake of LDL
decrease LDL, huge TAG decresae?, HDL slightly increased.
toxicity - yes. rhabdomyolisis.
What are pericytes?
Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries and venules throughout the body. … Pericytes help to maintain homeostatic and hemostatic functions in the brain and also sustain the blood–brain barrier.
Pericytes and their stem cell potential in the brain: Pericytes are multi-functional cells located within the basement membrane that surrounds capillaries throughout the body. They can regulate blood flow, are involved in angiogenesis and inflammation, and display stem cell-like properties.
fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.
papillary muscles
The papillary muscles are muscles located in the ventricles of the heart. They attach to the cusps of the atrioventricular valves (also known as the mitral and tricuspid valves) via the chordae tendineae and contract to prevent inversion or prolapse of these valves on systole (or ventricular contraction).
subendocardial layer is not found in what two types of heart structures?
papillary muscles and chordae tendineae
diuresis?
increased or excessive production of urine
ANF stimulates
natriuresis?
excretion of sodium in the urine.
ANF stimulates
What causes Hypervolemia?
The most common causes of hypervolemia include: heart failure, specifically of the right ventricle. cirrhosis, often caused by excess alcohol consumption or hepatitis. kidney failure, often caused by diabetes and other metabolic disorders.
when is ANF released?
in response to increased pressure across atrial wall - stretch and Endothelin, a potent vasoconstrictor, stimulates ANP secretion and augments stretch induced ANP secretion.
Veins - are veins or arteries more numerous?
Veins - and caliber is larger - 70% of blood volume
walls thinner, more supple, less elastic
histologically - are seen as COLLAPSED structures - w/ irregular slit-like lumen unless special effort made
Are veins distensible?
Yes, can adapt to volune and pressure variations -
“capacitance” or reservoir vessels.
What does arginine vasopressin do?
The antidiuretic hormone in humans and most mammals is arginine vasopressin (AVP). AVP promotes the reabsorption of water from the tubular fluid in the collecting duct, the hydro-osmotic effect, and it does not exert a significant effect on the rate of Na+ reabsorption
Vascular capacitance?
refers to degree of active constriction of vessels (mainly veins) which affects return of blood to the heart and thus cardiac output. … Capacitance vessels are considered to be the blood vessels that contain most of the blood and that can readily accommodate changes in the blood volume.
Why veins are called blood reservoirs?
In addition to their primary function of returning blood to the heart, veins may be considered blood reservoirs, since systemic veins contain approximately 64 percent of the blood volume at any given time.
Vein structure?
tunica intima, media, adventitia - boundaries often indistinct
muscular and elastic tissue not as well developed as in arteries - but CT much more prominent
Classification of veins?
venules (post cap and muscular types)
small-med
large
What’s a venule, how formed?
When several caps unite - a venule is formed - 15 -20 um cylindrical vessel in diameter
layers of endothelium,
thin longit. retic fibers w/ fibroblasts
pericytes may be present
Similar to capillary - although caliber of vessel is larger
What happens in areas with post - cap venules?
imp sites of fluid exchange and leukocyte migration
Where/how are leukocytes collected?
in the lymph after exiting the caps of arteries or veins.
How does the lymphatic system work with the respiratory system?
The lymph is drained from the lung through two distinct but interconnected sets of lymphatic vessels. … Within the lung and the mediastinum, lymph nodes exert their filtering action on the lymph before it is returned into the blood through the major lymphatic vessels, called bronchomediastinal trunks.
lymph tissue of gut, bronchial walls, lymph nodes and thymus - what are the endothelial cells like?
cuboidal, incomplete intercellular junctions - permitting ready passage of lymphocytes to and from blood. Called HEVs - High endothelial venules
High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node (by crossing through the HEV).
intercellular junctions of post cap venules?
more sensitive to inflam agents - promoting leakiness of fluids and defensive cells in inflammatory response - eg histamine, serotinin, other substances known to increase vascular permeability)
muscular venules?
> 50 um - smooth muscle appears -
> 200 um - circular muscle forms layer 1 - 3 layers thick - - spaced with CT and elastic
THICK adventitia
small - med sized veins?
1 - 9 mm
tunica intima thin - endo cells short and polygonal, irregular shape
subendo - inconspicuous
no distinct internal elastic lamina
TUNICA MEDIA -thinner than in arteries - best developed in lower limbs
ADVENTITIA - thick - thicker than media, made of loose CT with longit. collage bundles and few smooth muscles - arranged in fascicles, longit along vessel.
Large veins
> 10 mm,
tunica intima - lining rests on thick subendothelial layer of CT
Media - poorly developed
Adventitia - THICK. 3 Zones -
inner - dense fibroelastic CT - course collage fibers - frequent spiral arrangement
Mid zone - many longit muscle fibers
outer - only course collag and elastic fibers
Large veins
> 10 mm,
tunica intima - lining rests on thick subendothelial layer of CT
Media - poorly developed
Adventitia - THICK. 3 Zones -
inner - dense fibroelastic CT - course collage fibers - frequent spiral arrangement
Mid zone - many longit muscle fibers
outer - only course collagenous and elastic fibers
Where are vaso vasorums found?
MANY in adventitia - providing nutrients and blood to veins.
Valves of veins?
prevent retrograde flow - formed by reduplcation of intima, strenthened by CT and elastic fibers -
covered in endothelium - arrangement differs on both surfaces.
between valve and wall in sinus - wall usually thin
different surfaces on valves?
current side - subendothelial CT has rich network of elastic fibers
generally valves lie against wall of vein, but when regurg occurs - valves distend, free margins coming into contact - backflow prevented
since venous wall is dilated on cardiac side of attachment, veins appear knotted when distended
Varicose veins?
caused (I think in part - may be sole reason?) by veins dilating and valve free margins can’t reach one another
Arteriovenous anastamosis?
some places (skin, etc) blood shunts from anterioles to venules w/o circulating through cap network. “AV SHUNT”
walls of shunt are thick, muscular, and lots of vasomotor nerve fibers
Glomus body? reg body temp
AV shunts in nail beds of fingers and toes and auricle of ear - branched and torturous - special organ formed called glomus
A glomus body (or glomus apparatus) is a component of the dermis layer of the skin, involved in body temperature regulation. The glomus body consists of an arteriovenous shunt surrounded by a capsule of connective tissue. Glomus bodies are most numerous in the fingers and toes.
What does constriction of AV shunt in skin cause?
lowers blood flow, conserves heat
if CLOSED - heat is lost, if OPEN - conserves heat
what does dilation in AV skin shunt cause?
increases heat loss
Can bacteria and tumor cells easily penetrate veins?
yes, thin walled - and three tunicas not well defined -
how is a varicose vein defined?
when diameter is greater than NORMAL - and is elongated and tortuous.
Where do vericose veins occur?
also in liver cirrhosist, portal vein, hepatic vein (see below)
superficial veins of lower limb
esophageal varices
hemorroids
varicose veins? are they ever caused by faulty valves as opposed to dilated veins?
Yes - often secondary valvular incompetence
valves also can not change size as veins dilate
What is a thrombosis?
formation of a blood clot, known as a thrombus, within a blood vessel. It prevents blood from flowing normally through the circulatory system.
Emboli?
Something that travels through the bloodstream, lodges in a blood vessel and blocks it. Examples of emboli are a detached blood clot, a clump of bacteria, and foreign material such as air.
incrased risk for varicose veins?
obese, familial, pregnancy
due to increased luminal pressure and weakened vessel wall support
tend to be blue and bulge - tortuous
Additional sites of varicosities?
liver cirrhosis,
portal vein obstruction
hepatic vein thrombosis - cause portal vein hypertensions - porto systemic shunting increases blood
butt, gut, caput
What is main cause of portal hypertension?
Cirrhosis
When is a hemorroid thrombosed?
External hemorrhoids can become thrombosed (develop blood clots inside) and become very tender. Large blood clots can produce pain with walking, sitting or passage of stool. It is not clear why healthy people suddenly develop clots in external hemorrhoids
What are hemorroids associated w?
constipation and pregnancy
can be complicated by bleeding and thrombosis (pain)
When internal elastic membrane genetically fails to be produced, what are the two disorders?
Marfan’s - fibrullin - forms ELASTIC fibers
Ehler -Danlos Syndrome - lack of collagen type V
ZEBRA - 5 Zebras - (collagen type 5 - make 1 and 2)
Marfan’s - fibrullin
essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffold for deposition of elastin.
Ehler -Danlos Syndrome - lack of collagen type V
Classical Ehlers-Danlos syndrome (EDS) is characterized by skin hyperelasticity, joint hypermobility, increased tendency to bruise, and abnormal scarring. Mutations in type V collagen, a regulator of type I collagen fibrillogenesis, have been shown to underlie this type of EDS
The EDS community adopted the zebra as its mascot because “sometimes when you hear hoofbeats, it really is a zebra.”
Skin. Soft velvety-like skin; variable skin hyper-extensibility; fragile skin that tears or bruises easily (bruising may be severe); severe scarring; slow and poor wound healing; development of molluscoid pseudo tumors (fleshy lesions associated with scars over pressure areas).
Tunica media is under what nerve control?
sympathetic - “vasomotor tone” - one method of controls our blood pressure -
Does collagen contain elastin?
Elastin is also a protein found in connective tissues—but a different type of protein than collagen. It has the actual property of being elastic. It’s responsible for allowing tissues in the body to “snap back” to their original shape after being stretched or contracted.
Fibrillin?
is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffold for deposition of elastin.
Type of connective tissue in tunica adventitia?
tertiary syphilis destroys VV (vaso vasorum)- VV/VD
Dense irregular CT - with vaso vasorom - also supplies some of tunica media
tertiary syphilis - destroys these v vasorom - destroys blood vessels - which means adventitia dies, and blood vessel wall weakens leading to dissections and aneurysms
main differences between arteries and veins?
tunica media - much thicker in arteries
adventitia THICK in veins
Lumen - collapsed - veins when see on slide
internal elatisic lamina - much more prominent in arteries
3 types of capillaries - sinusoidal:
sinusoidal - liver, spleen, bone marrow -
huge clefts in endothelial cells (intercellular clefts) RBC, plasma, albumin can leak out - in both layers - epithelial and basal lamina
continuous capillaries? LEAST permiable
SKIN, Muscles, BBB, lungs
small clefts (exception is BBB where have tight junctions)
have PERICYTES - believe control endothelial cell growth, constriction, phagocytes, and pericytes - blood
small things can leak out and PINOCYTOSIS - transcytosis
so passage via pinocytosis and passive diffusion
Fenestrated capillaries?
medium intercellular clefts, fenestration pores in endothelial cells - no blood cells can leave, but sollutes and plasma can leave
Pinocytosis possible
Kidneys, glands - exocrine (ducts) endocrine (no ducts - ductless)
microcirculation
terminal arteirial = feeding into AV shunt
metearteriole, true capillaries (where arch happens),
A metarteriole is a short microvessel in the microcirculation that links arterioles and capillaries. Instead of a continuous tunica media, they have individual smooth muscle cells placed a short distance apart, each forming a precapillary sphincter that encircles the entrance to that capillary bed.
vascular shunt - drained by post capillary venule
sphincters in true capillaries?
pre-capillary sphincter - sympathetic and chems control - when contracted, blood can’t enter true capillaries
Albumin, what does it have to do with water in blood stream?
keeps blood in blood stream.
Albumin, the main protein produced in the liver, has numerous functions in the body, the most important of which is maintaining intravascular colloid osmotic pressure (COP). COP helps fluid stay within the vasculature instead of leaking into tissue.
carotid bodies?
near common carotid -
chemoreceptor reads oxygen levels -
hypertension and plaque?
People with high blood pressure are more likely to develop coronary artery disease, because high blood pressure puts added force against the artery walls. Over time, this extra pressure can damage the arteries, making them more vulnerable to the narrowing and plaque buildup associated with atherosclerosis.
Renin secretion from kidneys?
Increases BP, increases Angiotensin 2
causing vasoconstriction mechanisms -
Increases - BP - juxtaglomera apparatus cells respond to NE - increases angiotensin 2 - increasing BP in number of ways - increasing aldosterone, ADH production, causing vasoconstriction mechanisms -
What causes high blood pressure? various - primary vs secondary
3 main -
hyperactivity
in symp nervous system
hyper activity in renin production
decreases sodium excretion (elder, Afric/Am)
hypersensitive nervous system - constricts vasoconstriction in arterioles -
Renin production heightened
SA node increases heart rate - and force of cardiac output
low renin hypertension (elderly and afro americans) Less salt in urine - increase in sodium retention - blood volume increased
Risk factors of people with hypertension?
25 - 55 yo - if outside of age range - probably NOT primary
primary - diabetic obese type A people sedentary obstrutive sleep apnea disorder vitamin d deficiency alcohol smoking ethnicity
secondary causes of hypertension? 5% - not 25 - 55yo
Kidney - disease of renal tissue -
high BP and kidney - kidney has various ways to deal with
Intrinsic MYOGENIC
GFR mechanism (renin + restricting afferent via ca)
vs extrinsic systems
- VASOCONSTRICTION of afferent
protects kidney - too high flow can damage kidney and system in general
afferent delivery system, when stretched contracts delivery system to lower amount of blood coming in. -
smooth muscles contracting delivery system - sodium into smooth - release calcium, combine calmodulin, light chase kinase - contract
Low BP and kidney w/ afferent supply? not good
allow vasodilation - relaxes afferent
If too much salt coming through kidneys?
GFR high? over 120 - too much coming through
GFR is high - prox convoluted tubule cells - little hands catching all sodiums - many will make past - more than normal thru loop of henley
Goal of prox convoluted - to not let too much sodium to pass, but if there is SO much sodium, a lot will get by -
so how to stop this?
when sodium chloride gets by
macula densa cells - chemoreceptors - say OH NO too much, lots of sodium and chloride -
Sodium flows in cells, voltage goes up, atp released - leaves cell, converts to ADENOSINE - goes to
mesangial cells - help w/ phagocytosis, etc - adenosine activate g protein - stim SER - creates calcium
Calcium goes to
JUXTAGLOMERUAL cells (connected to mesangial cells via gap junctions) - releases RENIN
Calcium flows to juxta, in juxta there are granules, ca stim RENIN granules to fuse w/ membrane - renin granules released.
AND mesengial cells also connected to smooth muscle around vessels - constricts vessel, restricts blood flow - gfr rate reduced, sodium reduced
GFR levels?
kidney level
What is the normal GFR level?
Generally: In adults, the normal GFR number is 90 or higher. Having a GFR between 60 and 89 may be normal for some people, including those over age 60.
Glomerular filtration rate (GFR) is a measure of the function of the kidneys. This test measures the level of creatinine in the blood and uses the result in a formula to calculate a number that reflects how well the kidneys are functioning, called the estimated GFR or eGFR
if GFR low - ?
macula densa not cause restriction - they dilate - so more blood flow, more sodium.
Also, Macula densa releases NO and Prosteglanda e too - which relaxes smooth muscle
What does the macula densa do?
Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release
Extrinsic mechanism when Low BP?
Systolic < 80 - baroreptors in carotids - sympathetic - in carotid and aortic sinus - two nerves - glossophangeal (carotid sinus) and vagus (aortic sinus) nerve -
decreases GFR - odd because would think would want GFR to go up! but no, because symp is trying to save system.
on kidney, alpha 1 adrenergic receptor on smooth - CONTRACT powerfully, constricting urine, telling kidney to stop working - because symp trying to save body organs - not the kidney
need to keep urine inside to maintain systemic blood pressure - stops it from leaving
symp nerve also goes to juxta cells Beta 1 adr. - stimulates ca - stimulates renin release -
Renin - enzyme - liver producing angiotensinogen
renin takes amino acids from angiotensinogen -
NEED TO DO THIS.
What is renin?
Renin, which is released primarily by the kidneys, stimulates the formation of angiotensin in blood and tissues, which in turn stimulates the release of aldosterone from the adrenal cortex. Renin is a proteolytic enzyme that is released into the circulation by the kidneys.
What does aldosterone do?
Aldosterone is a steroid hormone. Its main role is to regulate salt and water in the body, thus having an effect on blood pressure.
Aldosterone is a hormone produced in the outer section (cortex) of the adrenal glands, which sit above the kidneys.
arteries in the neck, what can they do?
Carotid bodies
carotid body - at bifurcation - chemoreceptor - measures O2 levels
carotid sinus - proximal internal carotid artery - baroreceptor sensitive to BLOOD PRESSURE -
Sensitive to low oxygen tension, high carbon dioxide and low pH of arterial blood
glossopharyngeal n (CN IX), vagus CN x
What types of cells are carotid bodies?
glomus cells (type 1) and sheath cells or sustentatular Type 2) w/ rich vascular supply - caps fenestrated - lots of nerves
aortic and jugular glomeruli - similar in structure to carotid bodies
What is the carotid sinus?
The carotid sinus is a dilation at the base of the internal carotid artery. The nearby carotid body is a fibrous-covered structure that rests posteriorly to the carotid bifurcation. The blood supply to carotid sinus is by the vasa vasorum vessels.
BARORECEPTOR - tunica media thinner - adventitia thicker - lots of nerves - glossopharygeal nerve - stim by stretching -
thus reacting to changes in pressure -
blood - lecture 1
x
What are humoral agents/
Cellular immunity involves the development of immune cells that are able to recognize, bind, and kill other cells that have previously been infected by foreign infectious agents. THE HUMORAL IMMUNE SYSTEM. The word humoral refers to fluids (Latin - humors) that pass through the body.
blood
cells (rbc, wbc, platelets -thrombocytes)
plasma 55%
hematocrit
% rbc men 40 50%,
women 35 - 45%
Low crit - anemia or blood loss
buffy coat
wbc + platelets
supernatant part of blood (plasma)
denoting the liquid lying above a solid residue after crystallization, precipitation, centrifugation, or other process.
plasma contents
Serum and plasma both come from the liquid portion of the blood that remains once the cells are removed, but that’s where the similarities end.
Serum is the liquid that remains after the blood has clotted.
Plasma is the liquid that remains when clotting is prevented with the addition of an anticoagulant PLENTY of PLasma
albumin fibrinogen immunoglobulins lipids hormones vitamins and salts
anticoagulant
heparin or sodium citrate
serum, blood clot
protein rich fluid lacking fibrinogen
blood clot - fibrin containing network trapping blood cells
see chart re % of components
Plasma has -
water, plasma, hormones, other -
WATER 92%
PLASMA 7%,
albumin 60%, liver transport and osmotic concentration
globulins 38% plasma cells - immunity
alpha -liver - transport
beta - liver - transport
gamma plasma cells - immune
fibrinogen 7% Liver - clotting
HORMONES/enzymes <1%
other 1%
Formed element of blood 37 -54%
rbc, wbc <1, platelets <1
RBC 99% - red bone marrow, non specific immunity
WBC<1% -
granular, made in red bone marrow - non-specific immunity function
leukocytes:
neutrophils
eosinophils
basophils
agranular leukocytes:
lymphocytes, monoctyes
Lymphocytes - bone marrow and lymph tissue - specific immunity
Monocytes red bone marrow - non specific immunity
PLATELETS - Megakaryocytes - red bone marrow - hemostasis
Hemostasis
Stop Bleeding - stop blood flow
megakaryocyte
“large-nucleus cell”) is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting.
RBC qualities?
no nucleus, nor organelles - only plasma membrane , cytoskeleton, hemoglobin and glycolytic enzymes
How are senescent (OLD) rbcs removed?
phagocytosis or hemolysis in spleen
reticulocytes?
baby rbcs - complete hemoglobin synthesis and mature 1 -2 days after entering circulation - accoutns for 1-2% of circulating rbcs
what do rbcs transport?
oxygen and co2, are confined to circ system
see chart re how rbc is circulated
from marrow - destruction to
globin- amino acids, recycled
Heme - bilirubin and iron recycles via trasferrin to liver to marrow
where can old rbcs be broken down?
Liver mainly - using macrophage -
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized macrophages located in the liver, lining the walls of the sinusoids. They form part of the mononuclear phagocyte system.
the liver is the main organ of RBC removal and iron recycling is surprising, as is the fact that the liver relies on a buffer system consisting of bone marrow-derived monocytes that consume damaged red blood cells in the blood and settle in the liver, where they become the transient macrophages capable
Where are old red blood cells broken down?
Old or damaged RBCs are removed from the circulation by macrophages in the spleen and liver, and the hemoglobin they contain is broken down into heme and globin. The globin protein may be recycled, or broken down further to its constituent amino acids, which may be recycled or metabolized.
macrophages re rbcs are found where?
liver, spleen, red marrow
hemoglobin (Hb) characteristics
four subunits - globular protein -
adult HbA - a2b2
2a-globin, 2b-globin
FETAL - HbF - a2y2
Pulls 02 from maternal blood into fetal blood - o2 affinity of hbF is higher - explained by 2,3-BPG
shape of RBC maintained by what “band”?
spectrin, Band 3 proteins
integral and peripheral - arrangement contributes to elastic properties
integral member proteins -
glycophorins
band 3 proteins -
PERIPHERAL membrane proteins - inner surface of membrane - lattice network -
spectrin, actin, Band 4.1, adducin, Band 4.8, trpomyosins
Lattice network bound by andyrin - acticing with band 4.2 and band 3
defects in cytoskeleton?
elliptocytosis and spherocytosis - common features - anemia, jaundice, splenomegaly
spenectomy is normal cure
elliptocytosis - defective spectrin
autosomal dominant disorder - defective spectrin - abnormal binding
spherocytosis - deficient in spectrin or andyrin
autosomal dominant - deficiency in spectrin or andyrin
hereditary spherocytosis
causes decrease in rbc surface - most common defect involves ankyrin
non-deformable cells -
shedding of membrane vesicle
trapped in splenic cords and phagocytosed by macrophages
Howell-Jolly bodies - megaloblastic anemia
Howell-Jolly bodies occur where there is no spleen or an non-functioning spleen, referred to as asplenia. They are usually one of these at most in a red cell, round, dark purple to red in color and often located peripherally on the red blood cell. … It’s also the most common infection in patients with asplenia
Howell-Jolly bodies are nuclear remnants that are found in the RBCs of patients with reduced or absent splenic function and in patients with megaloblastic anemima
Hyperchromic spherocytes?
Hyperchromia means increase in color. The only cells that are truly hyperchromic are spherocytes. Spherocytes are the only cells that contain more hemoglobin than normal in relation to the cell volume. … Cells located in the “too thin” portion of the smear may appear to be hyperchromic; however, this is an artifact
Anisocytosis? - anemia causes
(RBCs) that are unequal in size. Normally, a person’s RBCs should all be roughly the same size. Anisocytosis is usually caused by another medical condition called anemia.
clinical features of hereditary spherocytosis?
What causes Hemosiderosis?
Hemosiderin is one of the proteins (along with ferritin) that stores iron in your body’s tissue. Excessive accumulation of hemosiderin in tissues causes hemosiderosis. This condition is different from hemochromatosis, which is an inherited condition that causes you to absorb too much iron from food
- Hemosiderosis (excessive accumulation of iron deposits)
The lungs and kidneys are
often sites of hemosiderosis. - anemia
- splenomegaly
- jaundice
- rbcs show increased osmotic fragility
- parvovirus b19 infects and destroy rbcs in marrow triggering recurrent aplastic crisis -
supportive treatments
transfusion or splenectomy (risk infection) - partial option
clinical features of hereditary spherocytosis
Splenomegaly with a Mild to Moderate Hemolytic Anemia, Increased Bilirubin and an Increased Risk for Jaundice and Pigment Gallstones Secondary to Chronic Hemolysis, and Increased Risk for Acute Red-cell Aplasia Due to Parvovirus B19 Infection
Laboratory Testing Shows Increased Osmotic Fragility and Normal MCH with Increased MCHC
Treatment Is with Splenectomy
sickle cell? valine at 6th
glutamic acid replaced by valine at 6th position
disc rigid, less deformable - severe hemolytic anemia and obstruciton of postcap venules
Thalassemia syndromes/
defective synthesis of alpha or best chains -
heritable anemia - defective synthesis of alpha or best chains -
anemia - defined by defective synthesis of hemoglobin molecule and hemolysis
hemolysis
the rupture or destruction of red blood cells.
sickle cell anemia - homozygotes vs. heterozygoes?
hetero - half of HbA replaced with HbS -
homo - all HbA replaced
Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that allele (is homozygous).
sickle cell is it on Beta and Alpha chain?
Looks to me like only on beta?
blood smear and sickle cell?
anisocytosis (variation size)
poikilocytosis (vary in shape)
Target cells - dense stained center, pale ring, dark encircling band
reversible vs. irreversible sickling?
distortion of membrane by each sickling episode - leads to influx of calcium, -> loss of potassium and water -> damages membrane skeleton
Alpha-thalassemia?
impaired production of hemoglobin,
a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood.
results in reduced amount of HbF and HbA - since there is reduced synthesis of aglobin subunits
Beta -thalassemia?
People with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body.
Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body.
alpha vs beta thalassemia?
Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains.
can someone have both alpha and beta thalassemia?
Yes – both alpha and beta thalassemia – Hgb A2 is elevated indicating beta thalassemia. More profound microcytosis than expected and gene mutation (so alpha thalassemia). Normal Hgb because it is a balanced mutation
What are the symptoms of someone with beta thalassemia?
tiredness. shortness of breath. a fast heartbeat. pale skin. yellow skin and eyes (jaundice) moodiness. slow growth.
abnormal number - high or low - of rbc?
Polycythemia
low number - anemia
high number - often people at high altitude
Polycythemia dangers?
blood viscosity increased -
What is Macrocytosis a symptom of?
nutritional deficiency, specifically of folate or vitamin B12.
hereitable- if gut can’t make intrinsic factor
greater than 9UM
Usually, macrocytosis is caused by nutritional deficiency, specifically of folate or vitamin B12. This can arise from a hereditary condition called pernicious anemia, in which a protein called intrinsic factor is lacking in your gut. Intrinsic factor helps your body absorb vitamin B12.
different types of anemia?
usually asso w lack of rbcs, but can also be rbc normal in number but lacking hemoglobin - hypochromic anemia.
also can be thru blood loss
hypochromic anemia? different types of anemia?
lacking enough hemoglobin in rbcs - usually due to iron deficiency OR
accelerated destruction of rbcs
OR
insufficient productino of rbcs
anemia treatments?
iron, b12, folate
how does Iron supplement work?
increass serum iron - and iron stored in liver and bone -
iron crucial for normal rbc prodcution and forming proteins, such as hemoglobin
b12, folate?
crucial for DNA synthesis and generating new rbcs (
erythropoiesis?
generating new rbcs definition
megaloblastic anemias -
skips division - abnormally large cells
when folic acid dependent or v b12 dependent synthesis is impaired in immature rbcs -
b12 and folate - are they needed for DNA or RNA synthesis?
both
inadequate vitamin? how affect mitotic division?
skips division - abnormally large cells
erythropoietin? KIDNEYS
normally produced in kidneys in response to decrease in blood flow tension - stiumlates erthropoiesis - (rbc prodcution) and increasese hematocrit.
some drugs can stiumlate this
filgratim and pegfilgratrim - ?
stim proliferatin, diffentiation and migration and functional activity of neutrophils
sargramostim?
stim proliferatin, diffentiation and functional activity of neutrophils, MONOcityes and MACROphages
Leukocytes?
two groups -
granuloctyes (specific granules)
agranulocytes (lack specific granules)
BOTH have nonspecific azurophilic granules, which are lysosomes
diapedesis?
leukocytes leave bloodstream and enter CT by homing mechanism - where perform functions and most die by apoptosis
numbers of leukocytes, neutrophils, etc?
leukocyte - 6000 - 10000
neutrophils 5000 - 60-70%
eosinophils 150
basophils 30
lymphocytes 2400
monocytes 350
platelets 300,000
Reticulocytes? 1% of rbc
are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells.
granulocytes? 3 PHILS
neutrophils
eosinophils
basophils
NON-dividing, terminal cells - life span of few days - die by apoptosis in CT
agranulocytes - ?
moncytes, lymphocytes
Neutrophils?
females Barr Body
most common wbc, 60-70 -%
first cells to migrate to the site of the infection to begin killing the invading microbes
nucleus - 2 - 5 lobes linked w/ chromatin fine threads; few organelles but granules - small golgi, few mitochondria
chromatin - hertochromatin at periphery, ehcromatin in center - females Barr Body forms drumstick shaped appendange on lobe
