He Microanatomy, Block II NotesAs performed by

Blood: What is blood?A mix of a whole different bunch of crap. Also, it’s considered a connective tissue.

Hematocrit: This is the measure of VOL of RBC/ VOL Total Blood. For males, this is around 40-50%, (.4-.5) and for women it’s 35-45%. For newborns, they have more blood/volume, so the number if 45-60%, but 35% for children under 10.

Polycythemia: This is an increased hematocrit. POLY: many; CYT: cell, EMIA: blood. This may be due to physiological reasons, or due to disease.

Anemia: Decreased hematocrit. A-: without.

If you were to layer a blood sample to measure hematocrit, the RBC’s would be at the bottom. Right on top are the leukocytes (White Blood Cells, also called the buffy coat.) This would be about 1% of all the volume of the blood. Almost negligible. (is when calculating plasma vol.)

Leukocytosis: An increase in leukocytes (cytosis = an increase in cells)Leukocytopenia: A decrease of leukocytes (penia; lack)

An increase in leukocytes would be associated with… leukemia.

So what about the rest? It’s all PLASMA. Plama’s about 90% water, then about 7-9% have a few proteins that are important to know.

Albumin: Maintains the colloid osmotic pressure in the capillaries (this is the crap in the Plasma area of the plasma part of ECF in that whole plasma/ISF/ICF crapola thing.)

Globulins: three kinds: alpha (glycoproteins, HDL, ceruloplasmins, and prothrombins) and beta’s (tranferrin, LDL’s.) The third kind is gamma globulins; which are antibodies.

Fibrinogen: Major clotting protein. The rest is sodium bicarbonate, Ca2+, and other organic stuff like hormones, aa’s, and glucose. Be sure to know that:Plasma is the liquid portion of blood obtained if blood is anticoagulant-treated. Serum is the liquid portion of blood remaining after blood is allowed to clot.

DyeingDifferent techniques are used for seeing blood cells. Romanovsky-type stains:

These include Wright’s or Giemsa’s. These stains tell you the net charge on a particular blood cell. Eosinophilic cells: Stain orange-pink (contains acid, attracts base)Basophilic: stain blue (contains base, attracts acids)Azurophilic: Stains a deep purple.

Sizes of cells: KNOW THESE!Erythrocyte: 7.5 mLeukocytes:

Neutrophil: 12-15 mEosinophil: 12-15 mBasophil: 12-15 mLymphocyte: 6-18 mMonocyte: 12-20 mPlatelets: 2-4 m

On average, Erythrocytes are smaller then almost ALL leukocytes, (although lymphocyte size varies.) Platelets are tiny pieces of shit.

Relative Number of Cells: Oh dear God, KNOW THESE!

Erythrocyte: 4.1-6 x 106/LThat’s 4,100,000 per friggin MICRO liter. That’s a shitload. On the other hand, Leukocytes: 6000-10,000/LThe relative numbers (all are percentages of the Leukocyte concentration):

Neutrophils: 60-70%Eosinophil: 2-4%Basophil: 0-1%Lymphocyte: 20-30%Monocyte: 3-8%.

Quick Notes: Basophils are hella hard to see on a normal smear w/out a special stain. Also, there are more lymphocytes then neutrophils in a pediatric patient.

Platelets: 200,000-400,000/ L

So… WBC’s<<Platelets<<<<<RBC’s.

Quick Quiz: - What’re the components of plasma? - What’s it called when you have an increase of leukocytes? Decrease?- The differences b/t Plasma and serum?

ERYTHROCYTES (AKA RBC’S)- No nucleus, biconcave disk-shaped bag of hemoglobin (Hb.) The shape is good for surface to volume ratio for gas exchange. They live for 120 days. Removed in the spleen after death. The RBC diameter is: (fill in the blank)They should be both normocytic (normal size) and normochromic (normal color; eosinophilic) with a central zone of pallor (pale area.)

Sidenote: different phrases to know:Microcytic: small, Macrocytic: largeHypochromic: Less Hb than normal. Hyper: More Hb. Anisocytosis: Abnormal variations in size, Poikilocytosis: diversity in cell shape.

What abnormalities are there?:Hb Ones: Sickle Cell: (HbS): makes Hb less soluble in low oxygen content:What’s it look like: Sickle shaped cells. Creates sticky ends, etc. See biochem: Block I.

Thalassemia: AKA persistence of HbF, or diminished globin chain synthesisWhat’s it look like: target cells (the cells look like targets); and hypochromia, and microcytosis. Anemia occurs.

Mutations in gene encoding membrane cytoskeleton proteins:Mutation in Spectrin: Causes most forms of spherocytosis:What’s it look like: spherocytes, causes hemolytic anemia

Mutation in Spectrin, Band 4.1 and Band III: Gives rise to hereditary elliptocytosis (one of many)What’s it look like: elliptocytes, causes a MILD hemolytic anemia.

Newly created RBC’s don’t look like regular ones. They still have RNA in them, making them basophilic in those areas, in a normally eosinophilic RBC. These guys are stained with Wright’s stain, making them hella easy to identify. These guys are called reticulocytes, and once they’re stained, they’re called polychromatophilic erythrocytes.

In adults, these are about .8% of the RBC’s, and mature within 24 hours of circulation. There are a lot more in kiddie-smears.

Keep in mind: RBC’s also have antigens exposed at surface, which is needed to match for blood and tissue transportation.

Quick Quiz:- A thalassemia results in cells that look like what?- What’s an abnormal variation in blood cell size called?- What are the relative numbers of blood cell types? (All of them)

PlateletsThese guys are small, non-nucleated fragments of a larger cell called a megakaryocyte. They live about 10 days, and there’re about (fill in the blank)/L. Used for clotting.

You got two zones for these guys:Hyalomere: Light-blue staining zone. Lots of actin and myosin in this area, (largest concentration per size w/exception of muscle.) Once they’re activated, finger-like projections made of MF’s are derived and go to work. Granulomere: Azurophilic staining granule. There are:

Alpha granules: most abundant granule type w/fibrinogen, von Willebrand factor, and platelet growth factor among at least 20 different other things.

Delta granules (dense bodies): contain the non-protein molecules that are secreted to aggregate platelets like calcium, ATP, and ADP. Also, they take up Serotonin.

Lambda granules: Lysosomes. See Block I lysosome bullshit for this.

Platelets have a very thick glycoprotein coat (otherwise known as glycocalyx.) This is to secure that platelets will have good adhesion. The shape is mainanted (an ovoid) by a marginal band of microtubules. An open canalicular system facilitates relase of the granule contents.

How do platelets clot? The injured endothelial cells release von Willebrand factor and thromoplastin (a microanatomical

dog whistle) calling platelets to adhere. Platelets arrive and adhere to the subendothelial collagen, releasing their granules. The relase of this makes it easier for platelets to adhere to each other, and they start stacking up on each other.

Platelts attract even MORE to come through the release of ADP, and thrombospondin to form a plug. Platelets express platelet factors on the plasmalemma to provide a surface for assembly of coagulation factors.

Coagulation causes fribinogen to turn in to fibrin. Fibrin forms a reticulum that traps formed elements into a clot, which after the vessel is repaired, goes away.

LeukocytesWBC’s. These are the first and last line of defense. They use the circulatory system to get around. Two types exist:

Granulocytes: they possess granules (obviously) and respond to Romaovsky-type dye. The three different versions of this are neutrophilcs, eosinophils, and basophils.

Agranulocytes: They don’t have SPECIFIC granules, but may have azurophilic granules. The two types are lymphocytes and monocytes.

You can count the numbers by use of a differential count. Pediatric patients have greater number of lymphocytes from 2weeks to about 4 years old (60%) when they start declining. Normal levels are reached when they’re about 14 or 15.

Neutrophils:These are how big?Pink cytoplasm, and very, very lobulated nucleus. The life span is a few days, and the circulation is about 6-7 hours. The nucleus arises from band shape to a big lump of chromatin. The Barr Body (inactivated X chromosome) looks like a drumstick, so you can tell the sex from this smear.

The cytoplasm, as stated was pink. There are granules present, about .5 m in diameter.

The azurophilic granules: These are primary lysosomes which have myeloperoxidase, acid phosphotase, and other such enzymes.

The specific granules: .1-.2 m (smaller than the azurophilic.) There are a shitload of these, as they’re the most abundant in the neutrophil. These are kinda hard to see in a light microscope. These contain alkaline phosphotase, collagenase, lactoferrin, and lysozyme.

Specifically, neutrophils are THE first line of defense. They’re like a pissed off amoeba; actively phagocyting. They get into peripheral tissues by attaching to endothelial walls, then go through cell junctions by diapedesis. (dia: through, pedesis: to leap.) They ingest the bacteria in vacuoles, then dump the enzymes on the bacteria to form secondary lysosomes.

If the bacterium is first coated with IgG, this goes much faster. Also, a derivative of the complement system (C3b) binds to the antigen-antibody complex. Stuff that coats bacteria is called opsonsins.

After the phagocytosis, the granule shoots is load at it, and the pH of the vacuoles is lowered by proton pumps. This triggers the azurophilic granules to shoot ITS load. These are specific to the type of bacteria and cause an overload of oxygen, lysozyme destroying the cell wall, depriving bacteria of iron… etc.

Neutrophils don’t need O2, because they get their kicks from glycolysis. Ox Phos is NOT important for neutrophils. Also, all this stuff may occur extracellularly through neutrophil extracellular traps (NETS.)

Eosinophils:Size is… what?They last 3-4 hours in the bloodstream, but have a life span of about 8-12 days. The nucleus is BI-LOBED. The cytoplasm has about 200 specific granules/cell. These granules are larger than those in neutriphils. They contain a large amount of major basic protein in the crystalloid center, which accounts for the eosin affinity. Some of the enzymes are peroxidase, eosinophilic peroxidase, and acidphosphotase.

We’re not sure what they do specifically, but you see a lot more during parasitic infection and allergic response. Some antigen-antibody complexes are attracted to sites where basophils and mast cells hangout. This is most likely due to counteract the inflammatory effects of the histamines and other shit that the basophils and mast cells secrete.

Basophils:Smaller…Nucleus is segmented and you have an irregular number of lobes. The granules are the biggest of all granulocytes, are water soluble, and show little phagocytic activity. They have peroxidase, histamine, and herparin.

These guys have IgE receptors, which is the molecule that is responsible for allergies. When an allergen comes in, it combines with IgE on the surface of basophil, which releases histamine. These are derived from separate bone marrow cells.

Quick Quiz:- What is the process of phagocytosis in neutrophils? - What are the different visual features of the nuclei of the granulocytes? - What types of enzymes does neutrophils have? Eosinophils? Basophils?- What’s your pin number?

Agranulocytes: As can be understood from the name, there is NO granule… or is there?

Lymphocyte:Small cell w/dense round nucleus, surrounded by a thin cytoplasm. The size of the nucleus is about the same size as an entire RBC. Sometimes, there will be azurophilic granules, and they migrate all around the lymphoid tissues using the blood as the pathway.

There are three different types: B cells, T cells, and Natural Killer cells, and circulating stem cells.

B-cells: Come from Marrow (B for bone) which produce antibodies. These then differentiate into plasma cells which is part of the body’s humoral immune response.

T-cells: These come from embryonic yolk sac lymphocytes in the thymus (T- thymus.) These respond to antigens by either stimulating (called helper cells) or dampen (suppressor cells.) Another type is the killer cell (cytotoxic) which is used in cell-mediated immunity. These recognize antigens on the surface, and kill them.

NK cells: These look like lymphocytes,but are null w/respect to B or T cell receptors.

In a smear, about 70-85% of lymphocytes are T cells.

Monocytes:These are big honkers in a peripheral blood smear. They have a nucleus that looks like a horseshoe, and the chromatin is finer. The cytoplasm is usually stained grey-blue. They spend about a day and a half in circulation before going out to do their duty. - The cytoplasm has azurophilic granules. Monocytes that differentiate in tissues are differentiated into macrophages, that survive there for months. They phagocytize, and act as antigen presenting cells (APC) for the lymphocytes.

Lecture 2, Blood Cell Formation

Since blood cells only live for a short period of time, new ones are needed to replenish. QQ:RBC’s live for how long? What about platelets, and lymphocytes?

All of the cells of the peripheral blood (except lymphocytes) matures in bone marrow (hemopoiesis.) Lymphocytes may INTIALLY come from bone marrow (or yolk sac) but they mature in other lymphoid organs.

Fetal Hemopoiesis:B/t week 2 and 6 of gestation, blood islands form in body stalk and yolk sac. This is where blood formation occurs early on. These things produce Primite Erythrocytes, which are nucleated. After 6 weeks, the liver and spleen form definitive erythrocytes (i.e. anucleated) until bone marrow forms @ month 5.

After birth: Hemopoiesis in Red Bone Marrow. Red Bone Marrow: Found in all bones @ birth, but at age 4-5 (years) marrow in long bones becomes replaced by adipose cells resulting in yellow marrow.

Red marrow stays in verterbrae, ribs, skull sternum, bones of pelvis, and ends of long bones. - Pathological conditions occur where yellow marrow and liver may actively do hemopoiesis.

Vascular CompartmentsBlood that goes through the marrow sinuses (i.e. the blood vessels of the marrow) comes from capillaries in cortical bone and endosteum.

- Arterioles (coming from radial arteries) DIRECTLY connect w/sinuses. - Sinuses are lined with continuous endothelium, cells that regulate uninterrupted entry and exit of cells to and from marrow.Diapedesis of marrow cells occurs through, not between endothelial cells.

Hematopoietic compartment:Parenchyma: Surrounds the sinuses of the marrow, the hematopoietic stem cells, and maturing cells. The ECM of the HP Compartment is called stroma and is made up of:

-Reticular Fibers-Adventitial Cells (covering outside of sinus endothelial cells)-Adipocytes-Macrophages (a lot of times in center of “blood islands”-Fibroblastoid cells (that produce basement membrane)

The stroma is the key to coordination of blood cell development

Organization of HP Compartment:Kinda messy, but a few rules:

- Megakaryocytes (big-ass things that give off platelets) found IMMEDIATELY next to sinus- Erythrocytes produced MOSTLY near sinus- Granulocytes made in nests (or dispersed sheets of cells) in intimate contact w/stromal cell

processes. Usually away from vascular compartment.

Hiearchy of Blood Cell DevelopmentAll Blood cells come from pluripotent hemopoietic stem cells (PHSCs) which are .1% of pop. Of nucleated cells in marrow.

PHSC breaks off into multipotential HSC’s (MHSCs) which are CFU-S (GEMM, Granulocyte, Erythrocyte, megakaryo, monocytes) or CFU-Ly (Ly for lymphocytes.) MHSC give rise to limited potential progenitor stem cells.

ALL OF THE ABOVE have surface antigen CD34 allowing them to be isolated and identified.

Altogether, all stem cells represent a SMALL portion of entire marrow compartment. Of this, the break down is:

20-30% Erythroid precursos60-70% myeloid precursos10% lymphocytes, plasma cells, macrophages, and stem cells.

Stem cells circulate in peripheral blood; can’t be distinguished from lymphocytes. Also, 4-5 megakaryocytes are seen per 1000 nucleated marrow cells.

QQ:Describe blood flow through marrow sinuses.What is parenchyma? What is Stroma made up of?Describe the organization of the HP compartment.

ErythropoiesisGeneral rule of thumb: As you progress, a) Cells get smaller, b) nucleus gets smaller and disappears, c)finer chromatin is present at the beginning.

Occurs in an erythroblastic island (island of a macrophage.) - The macro helps extract nucleus (inaddition to eating dead RBC’s.)

Order of Erythrpoiesis1: PHSC CFU-S (GEMM) BFU-E CFU-E Proerythroblast Basophilic Erythroblast Polychromatophilic erythroblast Orthochromatophilic erythroblast Reticulocyte Erythrocyte

Proerythro: fine chromatin, 1 or more nucleoli (that are LIGHT), basophilic cytoplasm, perinuclear Golgi halo. (14-19 m)Basophilic Erythro: Clumped chromatin (spoked wheel) has blank spots, nucleoli not seen most of the time, and is basophilic in cytoplasm. (12-17m)Polychromatophilic Erythro: coarse, condensed chromatin. Cytoplasm muddy gray (mix of eosinophilic Hb/w basophilic cytoplasm) This stage, Hb starts. LAST stage of division (10-14m)Orthochromatophilic erythro: Nucleus dense heterochromatin (almost no euchromatin) cytoplasm ALMOST as eosinophilic as regular erythro, but w/tint of blue (8-12 m)Reticulocyte: Little bigger than regular erythro, nucleus is extruded, cytoplasm faintly basophilic, reticular network of RNA. (basophilic strands)

# of erythrocytes released from marrow each day = # destroyed by spleen. Macrophages degrade Hb, send iron to marrow via transferrin.

Platelets:Easy to see Megakaryocytes; basophilic, devoid of granules. Goes through replication but doesn’t divide, gets friggin’ huge. (Endomitosis.)

Non-platelet forming: Cytoplasm matures, resulting in increase in cytoplasm, reduct. Of basophilia, and shitloads of azurophilic granules. Granules cluster in small groups, and these compartments of granules bound by demarcation membranes.

- Membranes continuous w/plasmalemma. - Do these compartments hold prepackaged platelets? Not likely. Maybe membranes are used

as a membrane reservoir for future platelets.

Platelet forming: MK are on side of sinuses, and project cytoplasmic extension (proplatelets) into lumen. The granular info is sent to the end, as well as a MT ring, and it breaks off forming a platelet. You get 4000-8000/MK.

1 BOLD = you have to know structure

Granulocytopoiesis:This shit gets really complicated, really fast and it’s hella hard to do w/out actually SEEING this stuff. Get your ass in lab to see this.

Neutrophil:PHSC CFU-S CFU-NM CFU-Neutrophil Myeloblast Promyelocyte2 Neutro. Myelocyte Neutro metalyelocyte Neutro. Stab Neutrophil.

Basophil:PHSC CFU-S CFU-Basophil Myeloblast Promyelocyte Ba. Myelocyte Ba metalyelocyte Bao. Stab Basophil.

Eosinophil:PHSC CFU-S CFU- Eosinophil Myeloblast Promyelocyte Eosin. Myelocyte Eosin metalyelocyte Eosin. Stab Eosinophil

Myeloblast: Basophilic cytoplasm (no granules) light staining nucleus, “fine” chromatin, 5+ nucleoli. Promyelo: 1-3 azurophilic granules, some condensing of chromatin. Neutro. Myelocyte: Reduced # azure granules, no nucleoli, more condensed chromatin more secondary granules (neutrophilic or eosinophilic) nucleus round to oval. LAST STAGE TO DIVIDENeutro Metamyelocyte: little basophilia in cyto. Specific granules, kidney shaped nucleusBand Form: Full complement of specific granules, “horseshoe” nucleusNeutrophil: What does it look like?

What about the other two? Indistinguishable until the myelocyte stage. At that point, neutrophil will be salmon color (being paler than an RBC color) while the eosinophil will be a DARKER pink. Basophil will be pretty damn purple.

Monopoiesis:CFU-NM (CFU-GM,) same thing that gives rise to neutrophils, gives rise to CFU-M, for monoblasts. 55 hours, monocytes can form. Leave marrow to migrate to CT; they divide there too, but not nearly as much as in marrow.

Blood cell compartments:Body maintains pools of blood cells. In peripheral blood, granulocytes found inside blood vessels, thrombocytes found inside spleen.

Regulation:Factors are in cellular and extracellular environment of marrow. Marrow factors affect cells by humoral sginalling, or by cell-cell/cell-matrix contact. Additional factors are humoral agents from sources outside marrow.

Steel factor (stem cell factor): formed by stromal cells, inserted into their membranes and binds to tyrosine kinase receptor (c-kit ligand) on PHSC’s, MHSC’s, and progenitor SC’s. This interaction maintains stem cell compartments.

Early progenitor cells responsive to a lot more factors, but as cells mature, not as much. Interleukins: 1, 3, and 6 are main IL’s maintaining pop. Of PHSC’s and MHSC’s.

Erythropoitein important example of humoar factor, produced outside marrow affecting limited number of cells later in development. Epo inversely related to O2 tension in tissues.

2 DOn’t need to differentiate b/t different myeloplasts, and promyelocytes

Fo’ instance, at higher altitudes, Epo released and development of polycythemia triggered w/enhanced O2 carrying capacity. Polycythemia primary compensatory device for high-altitude living.

When first moving, reticulocytre count increases around 5% generating peripheral red cell mass more rapidly. Acclimatized individuals characteristically have high hematocrits, but normal or only slightly increased reticulocyte counts.

QQ: - What’s the order of erythropoiesis?- What’s the difference between polychromatophilic erythro and orthochromatophilic erythro?- How do macrophages recycle iron?- What is steel factor?

Lecture 3:Cardiovascular system: series of connected tubes where fluids go through. Two vascular systems are blood vascular and lymphatic.

The general layering of vessels go, from inside to outside:Tunica Intima, Tunica Media, Tunica Adventitia. Think ‘I,’ Inside = Intima.

Tunica Intima: Layer of simple squamous epithelium.

These have endothelial cells lining the lumen of the tubes (which can be blood or lymph in the lumen.)

Nuclei of endothelial cells bulge into lumen. Endo cells form a basal lamina. - also form a smooth luminal lining facilitating flow, and somewhat permeable barrier. There’s also a layer of subendothelial tissues. This is composed of loose connective. May also have various smooth muscle cells.

Media:Has smooth muscle cells, and CT. Lots of elastic fibers, and sheets of elastin.

Adventitia:Outermost, has collagenous CT and elastic fibers.

Elastic sheets may often separate the 3 layers.

Internal Elastic lamina: separates intima from media in arteries, arterioles, and sometimes large veins. External Elastic Lamina: Separates tunica media from adventitia in large muscular arteries.

Innermost layer walls nourished by nutrients from lumen. In bigger vessels, adventitia and media need to get nutrients from elsewhere. What does this?

Vaso Vasorum: branches that arise from the same vessel if it’s an artery, or from neighboring arteries for veins.

Sympathetic innervations?Causes SM to contract and constrict. Dilation = parasymp. Parasymp stimulation causes endo cells to release nitric oxide. Some other cells contain baroreceptors, chemo receptors, etc.

Arteries: Away from heart. Vessel wall thickness is about half the width of the lumen. Can be divided by size:

Large Arteries, i.e. Elastic Arteries:- Intima is thick, has simp. Squamous endo layer and a thin layer of SM cells in subendothelial.

- tunica media has lots of SM cells alternating with parallel fenestrated elastin. Elasticity needed for ventricular contraction. Systole, pressure causes elastin to expand, diastole recoils. - Adventitia is thin and collagenous. - An internal and external elastic lamina MAY be present, but can’t be distinguished b/t other elastic sheets. - Examples are: Aorta, Pulm artery.

Medium, i.e. muscular, distributing arteries:- Intima has scattered SM cells in subend layer b/t simple squamous endothelium. - Media is THICKEST w/ some elastic lamina. SM contracts assisting distrib. Of blood to

organs. - Adventitia is collagenous. Boundary b/t adventitia and surrounding CT not always apparent. - You CAN see the elastic laminas, since elastic sheets aren’t that huge in this guy. IN the

bigger MEDIUM arteries you can see the external elastic lamina. - Intercostal, thoracoacromial arteries are examples.

Small arteries and arterioles:For the purposes of UC Microanatomy, you don’t need to differentiate b/t small arteries and arterioles. BUT small arteries are bigger.

- Intima is a single layer of endothelia cells and almost no CT, and NO SM. - Media is 1 or 2 layers of SM cells (6 for small arteries.) Get signals from ANS resulting in

vasoconstriction and dilation. - Adventitia is small merging w/ surrounding CT- Internal elastic lamina can be seen in LARGER small arteries. External is kinda hard to see. - Arteriole endo cells have rod-shaped granules called Weibel-Palade granules.

o These guys have von Willebrand’s factor for blood clotting. If it’s not there, platelets don’t adhere and this can screw you up making you bleed profusely, otherwise known as hemophilia.

Going FROM the heart TO the capillaries, you go Big to medium to small.

Quick Quiz Hot Shot:Which vessels would you find an internal elastic lamina? External?What the hell’s the Vaso Vasorum?

Capillaries:Considered the FUNCTIONAL unit of the circulatory system. Exchange material b/t blood and

surrounding tissues. Composed of endothelia cells and basal lamina. Endothelial cells line vessels, and join by tight junctions and gap junctions.

Pericytes: has contractile filaments, and thought to be relatively undifferentiated cells capable of transforming to OTHER cells (replacement endothelial cells, fibro blasts SM cells, phagocytic stuff.)

- Also has a basal lamina fusing with the BL of the endothelial cells.

Capillaries have a diameter of 3-7 micro meter; enough for ONE, UNO, EIN, HANNA blood cell. Sinusoids are a subset of capillaries w/bigger diameters (30-40 m) and are tortuous, making for slow movement.

Found in: Liver, spleen, bone marrow, ant. Pituitary and lymph nodes.

3 divisions of each:Continuous: endo cells joined by tight junctions, continuous basal lamina. Lipid solubles go through cells, small water-solubles pass through pores. Pinocytic vesicles give evidence of transcytosis across. The least permeable, but vessels may “leak.”

Found in: Blood-Bran barrier (huge in tightness; NOTHING gets through)Also in muscle, CT and nervous tissue. Cont. sinusoids found in bone marrow.

Fenestrated: Literally means “window.” Has a whole bunch of little fenestrations across cytoplasm, and a thin diaphragm traverse it (EXCEPT in the glomerulus; no diaphragms there.) Basal Lamina is ALWAYS continuous.

Found in: glomerulus, small intenstine, endocrine glands. Fen. Sinusoids in pituitary.

Discontinuous: incomplete endothelial lining, incomplete BL. Has fenestrations w/out diaphragms, and gaps b/t adjacent cells. Macrophages show up a lot in these sinusoids.

Found in: Capillaries? Um… nowhere. Sinusoids? Liver, and also in spleen and lymph nodes.

Capillary bed: When arteriole reaches tissue, break up into a shitload of capillaries. Metarterioles are smallest arterioles, discontinuous SM, give rise to capillaries. SM controlled by precap sphincters. Arteriovenous shunts allow blood to bypass capillary bed. More than one arteriole feed into a single cap bed.

Endo cells also are involved with enzymatic/metabolic functions and prevention of blood clotting inaddition to lining.

QQ:- What’s a pericyte do?- What do the Intima, media and adventitia look like in a large artery? Medium? Small?- How does hemophilia happen? - What’s a pericyte do?

Veins:TO the heart, thickness about 1/5 to 1/10 the lumen; so it’s smaller.

Typically look more screwed up than arteries (less rigidity.) BP in veins MUCH LOWER than arteries. Varicose veins occur when the valves in your veins mess up. 70% of the total blood can be found in the venous system at any time. Can be divided into several sections; venules, medium veins, and large veins.

Venules: Intima: little to no subendothelial, all endothelial. Media: a few pericytes in small venules, 1 or 2 layers of SM in larger venules. Adventitia: relatively thjick, continuous w/surrounding CT.

Medium Veins:Intima: Thin, endothelial cells and small amount of subendothelial CT. Media: More SM than venules, less than arteries of about the same size.Adventitia: Pretty thick with some elastic fibers continuous w/adjacent CT.

Medium veins have valves which are extensions of the intima, consisting of a fibroelastic CT covered by both sides by endothelium.

Large Veins: Intima: Great developed intima. Media: Underdeveloped. Adventitia: Thick and well-developed.

Large veins have longitudinally arranged bundles of SM in the adventitia.

QQ: - What does the intima look like in a venule? Medium? Large?- What kind of capillary would you find in the Glomerulus? How does this differ than others of its kind?

HeartEndocardium = tunica intima.

Same dealy; underlying subendothelial layer. Specialized group called subendothelial next to myocardium, and has veins, nerves, SM, and conducting shit. Endo is thick in atria, thin in vents.

Myocardium = tunica mediaThis sucker is the thickest of all three in the heart, ESPECIALLY in the ventricles. This has CARDIAC muscle; not smooth.

Epicardium = tunica adventitiaHas elastic and adipose. Outer lining is simple squamous epithelium (mesothelium) covering the

heart. This secretes a serous fluid in the pericardial cavity. This layer is called the visceral

pericardium, continuous with the parietal pericardium covering the pericardial sac. Visceral also allows free movement of heart in the pericardial cavity.

Coronary vessels = Vaso Vasorum. Valves = extension of endocardium, have a system of collagen and elastic called lamina fibrosa, covered by endo.

@ base of the four valves, the lamina fibrosa forms the annulus fibrosus. This supports the valves, but it separates the atria and ventricles. Free edge of valves in place in the ventricles by chordae tendinae which in turn goes into the papillary muscles.

Papillaries contract before myocardium giving tension and stopping back flow.

To find the annulus fibrosus in lab, look at where all the shit intersect. At that intersection, that’s the annulus fibrosus; otherwise it’s the lamina fibrosa.

Impulse conducting system of heart is muscle fibers called Purkinje Fibers. Have perinuclear glycogen, giving them a pale appearance.

LymphFlushes the body of excess fluid from tissues. These are ONLY directed at the heart, so they return lymph to the bloodstream.

When in the lymphatic system, the fluid (lymph) has proteins, metabolites and WBC’s but ABSOLUTELY NO RBC’s.

These are kinda like veins, except they are connected to surrounding CT by anchoring filaments. The lymph system “Ellis Island” are the lymph nodes which filter the lymph before it goes to the bloodstream.

Lymph vessels too have valves, and the biggest ones could also have SM in the tunica media.

Portal Systems:Q: First off how does blood flow go in the body?

A: heart, arteries, capillaries, veins, heart. This is true, unless you’ve got a portal system and you want to fuck with people’s heads. Then it goes heart, arteries, capillaries, veins, capillaries, veins, heart.

This is to deliver products from 1 location right to another.

HEPATIC: First set of capillaries are in the digestive tract. These go into venules, but then branches off again into capillaries of the liver. The rest is normal.

Why? To pick up nutrients from the digestive tract, give ‘em to the liver.

Others are anterior pituitary, and kidney portal systems.

QQ: - What are the equivalent structures of the normal vessel layers in the heart (i.e. tunica intima,

media etc.)?- What’s the difference b/t lamina fibrosa and annulus fibrosus?

Pathology: Angiosarcomas: tumors of blood vessels from ENDOTHELIAL cells. Hemangiopericytomas: From Pericytes

Angiogenesis: Formation of new vessels; this happens in adults and fetal development. Angiogenic factors: Promote blood vessel formation; may be able to treat diseases in the future. Anti-angiogenic factors: Could be inhibitors of new blood vessel formation; could slow tumors.

Artherosclerosis vs. arteriosclerosis:

Arthero = thickening of tunica intima. Messes with the coronary arteries pretty bad. Steps in arthero: 1) Injury occurs in endothelium2) Monocytes attach to damaged area3) They go to the subendothelial locations, and switch on (become active.) 4) Macrophages build up cholesterol; now they’re called foam cells. 5) Platelets adhere to the endothelial surface6) Platelets (as well as endothelials) blow their load which includes platelet derived growth

factor (PDGF.) This is like platelet pheromone for SM cells of tunica media. 7) SM cells answer the call, go into the intima and proliferate. In the middle of this Smooth

Muscle orgy, they accumulate lipid and contribte to the foam cells. 8) SM cells produce an extra cellular matrix, which comes as plaques which secretes more

PDGF.

Arterio = hardening of the arteries due to SM muscle cells dying in the media. Also elastic fibers are broken down.

How to remember the two? Arterio has Rio in it. “Rio” was a song by Duran Duran, a shitty British New-Wave invasion band in the 80’s. They are really HARD to listen to. Therefore, arteRIOslerosis is the HARDening of arteries. ( done at 3:37 AM in the morning.)

AneurysmThinning of wall of blood vessel; balloon like extension causing stuff to rupture.

LECTURE 4: Immune System

2-8% of WBC’s are monocytes. When they leave the circ. System, they become macrophages.

Lymphocytes: 20-30% of WBC’s are lymphocytes. Like other cells, they’re bigger when they’re being developed, smaller when they’re all good.

Divided into B and T cells. B = Bursa (also can remember Blood)Precursor cells give rise to plasma cells (antibody producing cells humoral immunity)Plasma cells are basophilic in cytoplasm, have prominent Golgi Ghost in H&E. At EM level, plasma cells have shitload of RER and hypertrophied Golgo. No storage granules.

T = Thymus derived, for cell mediated immunity goodness. 2 classes; helper T’s (Th) and cytotoxic killer-T’s (Tc.)

Immunology is all about distinguishing yourself from not-yourself.

Antigen-presenting cells (APC’s) initiate immune responses. These include macrophages, B’s and dendritic cells.

For most antigenic reactions, both T and B are a go (T are cell-mediated, while B are humoral.) Both also form effector cells (go to work, and are short lived) and memory cells (they remember)

T-cells survey, eliminate non-self; examples of T-cell immunity:Delayed-type hypersensitivity (positive tuberculin reaction)Allograph rejection (organ transplant)Contact Sensitivity (poison Ivy)Graft/Host Disease

BTW: Know this:

B cells work by secreting proteins such as immunoglobulins (Ig’s) or antibodies attaching to and eliminating soluble and cell/tissue non-self’s.

IgA: Secretory antibody

IgD: ?IgE: allergic antibody (histamine)IgG: Serum antibodyIgM: First and biggest antibody (pentameric); the big poppa of Ig’s.

Oh yeah, know this too:

Immune system is complex; communication via cell-cell (antigen presenting,) also through chemical messages like cytokines, and proteins (antibody mediated T-cell killing.)