Mini 4 key concepts

Subcapsular sinuses (of lymph nodes)

channel within the lymph node lined by the endothelial cells along with fibroblastic reticular cells and allows smooth flow of lymph through them (this is where filtration happens)

Schematic of ABO Production

fucose transferase adds L-fucose (without it no antigens can be added at all, that is Bombay phenotype), galactosyl transferase then adds N-acetylgalactosamine (for type A), D-galactose (for type B) or nothing for O (frameshift mutation). Other blood groups have antigens that are proteins. This is for any cell not limited to RBC, we have antibodies due to bacteria in the gut

Hemostasis

formation of a clot: •Primary hemostasis: Vasoconstriction + formation of platelet plug •Secondary hemostasis: Activation of the coagulation cascades, leading to formation of fibrin meshwork for stabilization of the plug •Tertiary hemostasis: Plasmin mediated breakdown of the clot

Lymphoid tissue (non thymus)

framework is made of reticular fibers of type III collagen secreted by reticular cells Uncapsulated: tonsils, MALT, Peyer's patches, appendix Capsulted: spleen, thymus, lymphoid nodes

Merkel Cells

present in stratum basale, touch receptors

Excitation-Contraction Coupling (muscle)

three events occurring in the following sequence: 1.Action potential (excitation) transmitted from synaptic terminal to muscle membrane (in neuromuscular junction) propagates across plasma membrane to transverse tubule 2. T-tubule action potential produces a mechanical connection between DHB receptors (on tubule membrane) and Ryanodine receptors (on SR membrane), which evokes the opening of Ryanodine receptors and causes Ca++ release into cytosol. 3. Ca++ release initiates mechanical contraction. Tetanic contraction is increased frequency of skeletal muscle action potentials (more tension than slow twitch) due to Calcium being released from the SR faster than it is reabsorbed.

Hemoglobin

spherical with polar groups on surface, saturated with O2 in lungs and releases O2 in tissues, good buffer due to Hist, binds sigmoidaly and is controlled. High pO2 in artery leads to protein loading, while unloading due to low pO2 in veins. P50 is 26torr (wide range for P), at 100 torr heme is 95%, 30 torr it is 55%, so heme releases 40% of its O2. Little released without BPG.

The Genitourinary Tract (innate immunity)

flushing action of urine urine acidity vaginal secretions, lysozyme

Seven types of proteins that participate in controlling cell growth

(I) growth factors (II) growth factor receptors (virus's mutation may cause cancer) (III) signal-transduction proteins (IV) transcription factors (V) pro- or anti-apoptotic proteins (VI) cell cycle control proteins (tumor suppressors/brakes) (VII) DNA repair proteins (mutation here inc. probability of mutations in other types of proteins)

Melanocytes and skin color

"false" Dendritic cell from neural crest cells which makes melanin granules degraded by lysosomes soon after it enters keratinocytes. No melanin in top layer cells. Can replicate for life. Melanocytes synthesize the pigment melanin from tyrosine, tyrosinase is activated by UV light. The cells of darker skinned people tend to contain more melanosomes Skin color determined by: Melanin amount made by melanocytes and rate of melanin degradation

Extrinsic Eye innervation, action, and testing ($)

"superiors" are intorsion "inferiors" are extorsion H-test and action difference: "down/up" stays the same but "in/out switches"

vWF Complex

(During Primary Hemostasis) •Factor VIII is bound to vWF when inactive in circulation •Binding to vWF prevents degradation of factor VIII •Release of factor VIII from vWF is initiated by thrombin it promotes coagulation and prevents endothelium-platelet interaction

Outer cortex and Inner (Para) cortex of lymph node

(F=follicle, P=paracortex, Mc=medullary cords) Nodules with germinal centers contain a mixture of proliferating B cells, APCs, T-helper cells, and macrophages. B cells are concentrated in the outer cortex and T cells in the paracortex. The number and composition of follicles can change when challenged by an antigen and thus develop a germinal center.

The Penis

(Internal) Crura - proximal end of the penis surrounded by the ischiocavernosus muscle; anchors the penis to the pubic arch Corpora cavernosa - paired dorsal erectile bodies bound by fibrous tunica albuginea Corpus spongiosum - surrounds the urethra and expands to form the glans and bulb of the penis Erectile bodies: Corpora cavernosa (2 each with a deep artery and covered by tunica albuginea) and corpus spongiosum. Buck's fascia covers all three.

Innervation of genitalia and perineum in females

(a) Pudendal nerve, (b) Inferior cluneal nerve, (c) Obturator nerve, and (d) Genitofemoral and ilioinguinal nerves

CN X Vagus Nerve "The Wanderer" Pathway

*Vagus nerve exits cranial cavity through the jugular foramen. *BE/SVE axons innervate muscles of the pharynx, larynx and palate. *GVA axons from the inferior pharynx, larynx, thoracic and abdominal organs. *SVA axons (taste) from the root of tongue and epiglottic region *GVE axons (parasympathetic) to thoracic and abdominal viscera to left colic flexure. Synapse is in or around target organ.

Acute phase proteins

-a-fetoprotein low in down syndrome, high levels: hepatocellular carcinoma -protease inhibitor's keep neighbor cells from dying -a1-antiprotease important for lungs -ceruloplasmin low hints at Wilson's disease (renal and liver failure)

Osteoblasts

-synthesize the organic matrix of bone (collagen type I, proteoglycans, GAGs, and glycoproteins) - are cuboidal or columnar in shape, cytoplasm stains basophilic -lots of RER. Forms gap junctions with osteoblasts and mainly with osteocytes - cells having lots of secretory vesicles exocytose them to form osteoid ( uncalcified bone matrix) -cells secrete matrix vesicles which arise from PM into the osteoid. Matrix vesicles have lots of Ca and PO4 ions, ATPase, alk. Phosphatase, pyrophosphatase and numerous Ca pumps - Ca pumps transport Ca into vesicles and alk. Phos.& pyrophos. Cleave PO4 ions from extracellular matrix - As conc of Ca and PO4 increases, crystallization of CaPO4 occurs and growing hydroxyapatite crystals burst membrane of matrix vesicles. - hydroxyapatite crystals surround osteoblasts and act as sites of initiation . They grow rapidly and are deposited into gap regions of collagen thus mineralizing the matrix

Skeletal system development

1) Neural crest cells: part of the skull 2) paraxial mesoderm: Axial skeleton 3) Somatic layer of the lateral plate mesoderm: long bones of the limbs, shoulder girdles, pelvic bones, sternum A somite differentiates into a dorsalateral part (dermomyotome: dermis and muscle) and a ventralmedial part (sclerotome: Mesenchymal tissue: fibroblasts, cartilages, bones of axial skeleon) Paraxial mesoderm forms segmented series of tissue blocks on eachside of the neural tube, known as somitomeres (in head region) and somites (from occipital region caudally)

Functions of the lymphatic system

1) acts to reabsorb lymph from the interstitial space in order to prevent edema formation. 2) Destruction of bacteria and removal of foreign particles from the lymph by phagocytosis, mainly by macrophages present in the nodes. 3) Specific immune responses: In response to the presence of bacteria or other foreign substances, lymphocytes and other plasma cells participate in specific immune responses such as the production of antibodies 4) It also transports fats from the small intestine to the blood.

Cell types found in lymphatic tissue and MALT

1) dendritic cells (type of APC) 2) lymphocytes, most of these are B cells 3) IgA-secreting plasma cells 4) other APCs (macrophages, B lymphocytes) 5) Reticular cells (play structural role) 6) Follicular dendritic cells (in germinal centers)

Cranial nerves and locations

1-olfactory, 2-optic, 3-occulomotor, 4-trochlear, 5-trigeminal (ophthalmic (V1), maxillary (V2), and mandibular (V3)), 6-abducens, 7-facial, 8-vestibularcochlear, 9-glossopharyngeal, 10- vagus, 11-accessory, 12-hypoglossal facial nerve EXITS through stylomastoid foramen but ENTERS via internal meatus The frontal nerve is a continuation of CN V1, Ophthalmic. It gives rise to the supraorbital and supratrochlear nerves.

Types of Cartilage

1. Hyaline Cartilage - most abundant and contains collagen type II in its matrix 2. Elastic Cartilage- lots of elastic fibers and matrix materials of hyaline cartilage 3. Fibrocartilage -abundant type I collagen and matrix materials of hyaline cartilage

Phases of immunological action

1. Cognitive phase: cognitive functions mediated by Pattern Recognition Receptors, specificity is predetermined, same for all cells, limited in number, not expanded upon stimulation 2. Activation phase: phagocytes bind microbial PAMPs via PRRs, 3. Effector phase: diapedesis and chemotaxis: adhesion and directed locomotion, ingestion and digestion mediated by reactive oxygen species, phagocytes get bigger and more active releasing cytokines

Differences (histological) between cardiac and skeletal muscle ($)

1. Diad instead of triad No well-developed terminal cisternae (as in skeletal muscle), only small terminal cisterna present beside the T tubule. Together they are called diad (one terminal cisterna and one T tubule). Diads are located in the vicinity of Z lines; T tubules are larger and lined by external lamina. Triad found between A and I band. 2. Mitochondria in cardiac muscle cells: more and larger 3. Myofibrils: are not completely separated from each other due to the less developed sarcoplasmic reticulum.

Cells of innate immunity

1. Epithelial cells 2. Phagocytes: Macrophages, Neutrophils, Dendritic cells 3. NK cells

Epidermal Skin Appendages

1. Hair follicles and their product, hair. No nuclei. Proliferation of matrix cells accounts for growth of hair. Arrector Pili Muscle-goosebumps. 2. Sebaceous glands and their product, sebum. Holocrine secretion. 3. Eccrine sweat glands and their product, sweat. merocrine excretion. Dark cells line lumen, clear cells underneath excrete sweat, myoepithelial cells contract and excrete and are found on outer lumen 4. Apocrine sweat glands and their mixed product. Located in arm pit, the areola of the nipple, and the anal region

Basic mechanisms of heat balance ($)

1. Heat production Physical work: 75% heat, 25% work perf. (max 12 BMR) Internal work is 100% heat (eq) Thermoregulation (shivering) and Thermogenesis 100% 2. Heat storage Increases in Tb by a heat dissipation = 0 Heat capacity of a 70 kg body = 60 kcal°C Heat prod. at BMR : = 1,2 kcal/min (Tb increases by 1°C each 50 min) at max. Metabolic rate : = 11 kcal/min (Tb increases by 1°C / 5 min) 3. Heat dissipation Mainly through radiation then evaporation then convection/conduction Heat loss from skin: depends on thickness of insulating air layer (which is small by wind and at curved body surfaces) Heat conductivity of insulating layer Heat transport to the skin: Heat transport from body core to skin surface is regulated by the regulation of blood flow to the skin Most variable: finger then hand then underarm

Proteins of innate immunity

1. IFN-α,IFN-B, IFN-y: inhibition of viral replication and activation of NK cells 2. Complement 3. Acute phase proteins: C-reactive protein, Mannan binding lectin 4. Defensins

Mechanism of Bone Resorption

1. Inside osteoclasts, CO2 & H2O form H2CO3 by carbonic anhydrase 2. H2CO3 dissociate into H+ & HCO3- 3. HCO3- & Na+ enter capillaries 4. H+ is actively transported into subosteoclastic compartment reducing pH and acting on inorganic matrix 5. Released minerals enter into capillaries via osteoclasts 6. Enzymes (lysosomal) released outside act on organic materials of decalcified bone 7. Organic fragments are taken up and further broken down

Major cytokine families ($)

1. Interferons: interfere with virus replication (IFN-a,B,y) 2. Hematopoiesis/ growth factors: G-CSF (granulocytes) M-CSF (macrophages) GM-CSF (granulocyte/macrophage) SCF (differentiation of BM stem cells), IL-3,6,7,11 <-- JAK STAT 3. TNF family/ Tumor necrosis factor: TNF-a and TNF-b (lymphotoxin) pro-inflammatory 4. Chemokines: RANTES (Regulated on Activation Normal T cell Expressed and Secreted), Eotaxin (eosinophil selective), IL-8 (chemotactic; neutrophils!), SDF-1 5. Interleukins (separate card)

Growth of Cartilage : Two processes ($)

1. Interstitial Growth: Chondrocytes from within divide to form isogenous groups. Cells secrete new matrix which separate cells apart, thus increasing size of cartilage - occurs in early dev., in articular cartilage, and in epiphyseal plates of long bones Appositional Growth : Perichondrium is composed of a. outer fibrous layer with fibroblast cells and coll type I b. inner cellular layer (chondrogenic cells derived from mesenchymal cells). This layer will differentiate into chondroblasts. These cells are ovoid cells rich in RER, Golgi and lots of secretory vesicles. Maturation of chondroblasts form chondrocytes which are surrounded by the matrix (Fibrils & GS) secreted by chondrocytes

Histogenesis of Bone (two ways) ($)

1. Intramembranous Ossification (direct bone formation) 2. Endochondral Ossification ( indirect ) Bone grows only by appositional means Intramembranous: e.g. flat bones of skull and clavicle, Mesenchyme cells condense, osteogenic cells become osteoblasts secreting osteoid making trabeculae of bone and primary bone tissue. This is remodelled to make lamellar (compact) bone. Endochondral Ossification (must use hyaline cartilage) 2 phases: A) Hypertrophy and destruction of chondrocytes B) Osteogenic bud ( osteogenic cells & blood capillaries) penetrate spaces left by degenerating chondrocytes and osteogenic cells form osteoblasts

Contractile nonmuscle cells

1. Myoepithelial cells Associate with glandular secretory units, covering the surface of those units, basket-like shape Arise from ectoderm. Contain actin and myosin; Contraction is similar to that of smooth muscle (calmodulin-mediated) In mammary glands: contract in response to Oxytocin; In lacrimal glands: contract in response to acetylcholine 2. Myofibroblasts Contain actin and myosin and can contract. Wound contraction: decrease the size of the opening

Transmission sequences of action potential from a nerve to muscle

1. Nerve action potential depolarizes the presynaptic nerve terminal 2. Depolarization opens voltage gated Ca++ channels and calcium enters synaptic terminal 3. Ca++ entry causes vesicle membrane to fuse with presynaptic membrane and ACh is released 4.ACh binds with its receptors (two molecules per receptor) at post synaptic membrane and opens a cation channel 5. Na+ moves through cation channel into the cell and produces a depolarizing graded potential (end plate potential) which in turn opens voltage gated Na+ channels eliciting a muscle action potential Post synaptic potentials are graded. In skeletal muscle: An action potential spreads from the initiation site in two directions towards both ends of the fiber. • Action potentials do not pass from one skeletal muscle cell to another skeletal muscle cell (unlike the heart which can)

Cancer: Mutations or Overexpression of Growth-Factor Receptors ($)

1. Point mutation in Her2 receptor causes dimerization (const. active kinase) Many human breast cancers over-express a normal Her2 receptor. 2. Deletion of the ligand binding domain in EGF receptor leads to const. activation of the protein kinase. 3. Trk receptor replaced with the 221 N-terminal amino acids of tropomyosin, dimerization occurs and the Trk kinase is const. active in cytosol.

3 Functional States of Osteocytes:

1. Quiescent state osteocytes : scant RER, mature calcified matrix (osmiophilic lamina) close to PM 2. Formative State osteocytes : lots of RER, deposition of osteoid in pericellular space within the lacuna . 3. Resorptive State osteocytes : well dev RER & Golgi, and lots of secondary Lysosomes. This cell removes matrix (pericellular space is devoid of collagen fibrils) . Resorption by this mechanism where Ca is released to maintain blood Ca levels is called osteocytic osteolysis

Classification of skeletal muscle fibers (3)

1. Red: Type I slow but repetitive, not easily fatigued. Smallest diameter. Rich myoglobin. Largest density of mitochondria, oxidative phosphorylation. 2. White: Type IIB. fast but easily fatigued, largest diameter, poor myoglobin, least density of mitochondria, glycolysis. 3. Intermediate: Type IIA intermediate All skeletal muscles contain different ratios of the three types of fibers.

Vertebral defects

1. Scoliosis(lateral curving of the spine): Fairly common; two succesive vertebrae fuse assym. or have half a vertebra missing 2. Cleft Vertebra (spina bifida): One of the most serious vertebral defects is the result of imperfect fusion or nonunion of the vertebral arches.

Ab chain recombination rules

1. The rearrangements only occur between segments on the same chromosome. 2. A heptamer must pair with a complementary heptamer (nonamers also). 3. One of the RSSs must have a spacer with 12 bp and the other must be 23 bp (the 12/23 rule) or apoptosis occurs. D region recombines first then VDJ (for heavy chains, light chains only have one recombination type), things between D and J are lost. Reading frame of V-D-J must be kept intact or cell dies (no heavy chain made) Only one heavy chain recombination "run" due to loss of space, 1/9th of the recombinations will work for B cell. For light chains there are multiple possible attempts between V and J due to no D max number due to smaller # Recombination activation genes (RAG-1 and RAG-2), are necessary for the recombination!

Overview of Lymphatics: Drainage of the Abdomen

1. To axillary lymph nodes from region above umbilicus 2. To superficial inguinal lymph nodes from region below umbilicus 3. To lumbar lymph nodes from post wall of abdomen Nodes Divided from their location into: Parietal lymph nodes: lying behind the peritoneum and in close association with the larger blood vessels. Visceral lymph nodes: which are found in relation to the visceral arteries. Visceral nodes: 1. Celiac Nodes (stomach, duodenum, liver, pancreas, spleen) 2. Superior Mesenteric Nodes (Jejunum, Ileum, Cecum , Appendix, Ascending colon, Transverse colon) 3. Inferior Mesenteric Nodes (Descending colon, Sigmoid colon, Upper part of rectum)

Functions of the blood

1. Transports O2, CO2, hormones, waste, nutrients, enzymes 2. Stabilization of pH and electrolyte concentrations in interstitial fluids 3. Regulation of body temperature 4. Blood acts as a pathway for migration of white blood cells between various connective tissue compartments of the body Blood has three formed elements (WBC,RBC, platelets)

Primary Hemostasis

1. Vasoconstriction mediated by (Thromboxane A2/TxA2) 2. Aggregation + Adhesion of Platelets Factor VIII + Von Willebrand factor (vWF) 3. Release of Arachidonic acid 4. Induction for more platelets to aggregate 5. Binding of Thrombin to aggregated platelets 6. Activation of myosin light chain kinase enzyme, MLCK 7. Alteration of platelet shape 8. Platelet Plug formed

Recycling of the Vesicle membrane

1. Vesicle membrane is fused with the plasma membrane after exocytosis of ACh 2. Retrieval of vesicle membrane is carried out by clathrin-mediated endocytosis, which leads to the formation of coated pits that pinch off to form coated vesicles 3. The clathrin coat of coated vesicles is disassembled, and the recycling vesicles fuse with each other inside the synaptic terminal to form an endosome. 4. New synaptic vesicles then bud off from the endosome. 5. The new vesicle is refilled with Ach by transporter molecules in the membrane of the vesicles, which accumulate transmitter at high concentration inside the newly formed vesicles. The recycled vesicles are then ready for docking, priming, and a new cycle of exocytosis in response to presynaptic action potentials.

Nerves in the Skin ($)

1. free nerve endings- Receptors for fine touch, heat, cold, pain,itching 2. Merkel cells with their nerve attachments-touch 3.Pacinian corpuscles- deep pressure receptors 4. Meissner's corpuscle: touch 5. Ruffini's corpuscles: stretch

Epidermis layers (bottom to top) ($)

1. stratum basale: stem cells, inc. mitotic activity 2. stratum spinosum: prickle cells (desmosomes) Stratum basale and lower stratum spinosum form stratum germanitivum (only keratinocytes cells that divide) 3. stratum granulosum: most superficial layer with nuclei still present and has keratohyalin granules. Cells of the stratum granulosum and stratum spinosum also contain lamellar granules (water proof skin) may have melanocyte pigments if thin skin but not thick skin 4. stratum lucidum: in palmar/plantar thick skin, clear, keratinocytes with only keratin 5. stratum corneum: scale like squames (dead cells aggregates)

Immune response to extracell. bacteria ($)

1.Complement activated first (alternate and lectin pathways) 2.Inflammation: IL 1, IL 2, and TNF alpha act on blood vessels and the neutrophils there sense chemokines (IL 8) to leave the vessel and attack the bacteria. 3. Dendritic cell goes to lymph node to find T cell (with MHC II, CD 28 and CD 86 and T-receptor) if this hook up occurs with IL 1,IL 6, and TNF beta present then T cell becomes Th 17 which makes IL 17 and IL 2 (clonal expansion) IL 17 amasses neutrophils. Dendritic cell can also hook up in presence of IL 4 and make Th2 cell which makes more IL 2, IL4, and CD40. Or in presence of IL 12 to make TH1 which releases CD40 and INF-y Th finds B cell with CD40L and IL4 to make class switch. INF-y tells B cell to become an IgG. If IL-4 is displayed alone it becomes IgE, with TGF Beta it's IgA (if nothing stays as IgM). Opsonization occurs which recruits complement (classical path) and phagocytic cells have Fc receptors leading to cell death and pus formation.

Greatest diameters (pelvis) (rotation of fetus in birth canal)

1.Superior aperture: transverse: 13-13.5 cm (Rotation of the fetal head within the birth canal flexio, mentum sternum position) Amplitudo pelvis: oblique: 14 cm Inferior aperture: sagittal: 9.5-11.5 cm

Pharyngeal arches

Each has an artery, cranial nerve, and cartilage. There are 4 pouches inside and 4 grooves/clefts outside. The thymus goes from the foramen cecum to first tracheal ring level and parathyroid glands join it along with ultimobranchial body. The thymus from the third pouch also descends though more inferiorly.

Vertebral Artery

1st branch of the subclavian artery Has 4 parts: cervical, vertebral, suboccipital and cranial Cervical: medial to the scalene muscles Vertebral: ascends through the transverse foramen of C6-1 Suboccipital: lies in the groove of the posterior arch of C1 before entering foramen magnum Cranial: supplies the medulla, spinal cord, cerebellum, dura and posterior cranial fossa. The vertebral arteries join to form the basilar artery

Fetal Hb

2a and 2y chains, greater O2 binding and saturation than adult Hb, must steal O2 from mother, shift to the left. y chains have one Lys, one His, one Ser (instead of two His)

Langerhans Cells

APCs from bone marrow, member of the mononuclear phagocyte system The characteristics of the CT surrounding the newly formed macrophages determine their exact final differentiation.

Neutrophils (attack bacteria and fungi)

3-5 lobed nucleus. First to appear in acute bacterial infections. Dead neutrophils and bacteria form pus. Two types of granules: small, pale, peroxidase negative granule (secondary/specific granules release antimicrobial agents); and peroxidase positive azurophilic granule (primary granules, lysosomes that contain myeloperoxidase for oxidative burst). Also has collagenase. Neutrophils have few mitochondria and rely on glycolysis (aids in survival in anaerobic environments). Are active phagocytes recognizing bacteria via opsonization or chemoattractants. Initial wave and direct response to most bacterial and fungal pathogens: CR3 (innate immunity), PRRs, FcR (adaptive immunity) Killing: Highly phagocytic, Respiratory burs, Phagocytosis & Respiratory burst

Potent anticancer effect of 3-bromopyruvate ($$)

3-BP covalently modifies HK-2 so that it cannot bind to VDAC. AIF is then released from the outer mitochondrial membrane and enters the nucleus to induce apoptosis. 3-BP's mode of action extends beyond apoptotic effects appears to also involve necrotic events. The inability of HK-2 to bind to VDAC sets up a condition where ATP gets depleted and necrosis also occurs.

Dynamics of hemopoiesis

3rd-4th week of gestation: blood precursor cells arises from the yolk sac mesoderm 5th week: Liver and spleen are temporary hematopoietic tissues About 5th month of gestation: Bone marrow becomes increasingly important hematopoietic tissue After birth, blood cells derived from stem cells in bone marrow. The bone marrow also produces cells (T cells) that migrate to the lymphoid organs where they become immune competent

Inflammation (Acute)

4 classic symptoms: swelling, redness, heat, and pain. Acute inflammation is a rapid host response that serves to deliver leukocytes and plasma proteins (such as antibodies) to sites of infection or tissue injury. Three major components: increased in blood flow; plasma proteins and leukocytes to leave the circulation: loosening of capillary endothelial cell tight junctions; and emigration of the leukocytes from the microcirculation: diapedesis

Cells of Bone (Osteoproginator)

4 types 1. Osteogenic (osteoprogenitor) 2. Osteoblasts 3. Osteocyte 4. Osteoclasts Osteoprogenitor Cells - derived from mesenchyme - can differentiate into osteoblasts and if necessary under certain conditions into fibroblast and chondrogenic cells - are located in the inner cellular layer of periosteum, lining Haversian canals, and the endosteum . - are flat, inconspicuous cells with a pale- staining oval nucleus and sparse cytoplasm

Erythropoiesis 2 (Reticulocyte to RBC)

5. Reticulocyte (picture) -after it expels its nucleus. Still has a few polyribosomes that aggregate (when treated with dye cresyl blue) to form a stained "reticular" network. Reticulocyte leaves the bone marrow and passes into the bloodstream. 6. Erythrocyte: the mature form, has lost all polyribosomes nurse cell: phagocytoses and digests the discarded nuclei Also: marrow is not a storage site for erythrocytes Erythropoetin made by kidney and stimulates hematopoeisis ( acts on CFU-E receptors) and used in blood doping

Transaminases: AST and ALT

AST (asp): Present in high concentrations in cells of: Cardiac and skeletal muscle and Liver high levels hint at hemolysis, hepatitis (acute) and MI. It's ok in neonatal stage though. ALT (ala): Liver and skeletal muscle (duchenne's) high levels hint hepatitis (acute), cirrhosis, jaundice

Overview of Lymphatics: Drainage of the Breast

75% to the axillary nodes (pectoral or other groups) The rest drains to parasternal lymph nodes or subdiaphragmatic nodes Axillary node pattern: Pectoral to subscapular to central to apical to supraclavicular

Lymph Nodes

Each lymph node is a relatively small, soft structure that has a fibrous connective tissue capsule, Convex surface, Concave surface contains the hilum, which is the site of arteries and veins entering and exiting the node, Efferent lymph vessels also are in the hilum

BALT in the lung

A bronchiole (*) has a lymphoid nodule. This is a primary nodule which LACK germinal centers but does contain a densely packed, spherical cluster of lymphocytes.

Antigen

A molecule that is recognized by the immune system, a substance that can induce an immune response, usually foreign. At least 10,000 da, complex: best is proteins then polysaccharides, last is small molecules like lipids. Antigens have foreignness and solubility (or it will pass through unrecognized) Antigens that provoke and immune response are immunogens

Sources of ATP for Muscle Contraction

ATP is needed for three purposes: 1. the myosin power stroke, 2. for dissociation of myosin from actin and 3. to power the SR-Ca ATPase for calcium uptake and relaxation. The immediate source of ATP is free-ATP in the muscle cytoplasm (limited) The 2nd source of ATP comes from the transfer of phosphate from creatine phosphate (PCr) to ADP with the subsequent formation of ATP and creatine (4 mol/min but limited) The 3rd source of ATP comes from anaerobic glycolytic conversion of glucose to lactic acid, 2.5 mol/min. Not much but good due to large glycogen stores. The 4th source of ATP is from aerobic metabolism of pyruvic acid or fatty acid through oxidative phosphorylation. Like glycolysis, aerobic metabolism is slow (1 mole of ATP/min) but is able to generate ATP for extended periods of time (hours). Since free-ATP is the immediate source of energy for contraction, the supply of free-ATP is maintained by utilizing the three metabolic sources of ATP: creatine phosphate, anaerobic metabolism and aerobic metabolism

Optimal length

A range of muscle stretched lengths where active tension is maximum. On either side of the optimal length active tension is less. In the body skeletal muscle is held at its optimal length for active-force development by the tendons that hold it in place at its origin and insertion. Even though skeletal muscle active tension will change under experimental conditions when the muscle is stretched, changing the in situ muscle length is not a physiological way the body regulates active tension in skeletal muscle. In skeletal muscle passive tension increases extensively with increases in stretched length beyond the optimal length. If only difference between two muscles is length, then longer fiber has higher velocity during isotonic contraction than shorter one.

Endochondral Ossification (histogenesis) ($)

A) Hyaline cartilage gets bigger (has perichondrium), ossification starts in midline, perichondrium there becomes vascularized and chondrogenic cells become osteogenic cells (when osteogenic cells become osteoblasts next the perichondrium is called the periosteum). Intramembranous formation thus forms the subperiosteal bone collar Chondrocytes die and cartilage becomes calcified, lacunae form marrow spaces. The osteogenic bud (osteogenic cell and blood capillaries) enters collar due to osteoclasts and invades calcified cartilage, osteoblasts develop from osteogenic cells in dead chondrocyte space. Osteoblasts make primary bone and subperiosteal bone continues forming. Osteoclasts destory primary bone and calcified cartilage, lamellar bone is laid down. Epiphyseal cartilage is invaded at each end, distal invaded later but removed first.

Joints

A) Synarthroses- closely bound with minimal movement There are 3 types of synarthrosis 1) Synostosis: Skull bones 2) Synchondrosis: rib & sternum 3) Syndesmosis : pubic symphysis B) Diarthroses- bones are free to articulate over a wide range and these joints of extremities. Synovial membrane -2 cell types: Type A are macrophages. Type B cells are fibroblast - secrete the synovial fluid ( a plasma filtrate with lots of hyaluronic acid and lubricin).

Variations of Pelvis

A, android is a typical male pelvis B, gynecoid is a normal female pelvis Although both A and B can occur in women, but A is a serious threat for childbirth C, anthropoid it is more common in black women D, platypelloid is rare, occurs in both sexes

lymphoid nodules

AKA lymphoid follicles, dense aggregations of lymphocytes arranged as spherical, unencapsulated clusters (picture LN is entire line width)

Antibody: Basic Structure and phagocytosis trigger

Ab binds using binding sites made of light and heavy chain parts Ab secretion by plasma cells can lead to: neutralization by stopping adherence, opsonization (phagocytosis), and complement activation triggering phagocytosis: bacteria coated with complement and IgG, Ab binds to Fc receptor (when C3b binds to CR1), phagosome is created in macrophage and lysozyme destroys bacteria Ab is flexible to accommodate epitome spacing Proteolytic enzyme products explain that only Fcy can cross placenta to fetus (Fcy is bottom half of Ab in gamma form)

Degradation and recycling of Acetylcholine

Acetylcholinesterase is present at the surface of motor end plate and causes the break down of acetylcholine • The break down product choline is transported back into the synaptic terminal by a specific membrane carrier • In the synaptic terminal, ACh is synthesized from choline and acetylcoenzyme A through the effects of the enzyme Cholinacetyltranferase. • ACh is then transported into the uncoated vesicles and undergo priming before next cycle

Recycling of vesicles

Adaptin molecules of clathrin (adaptin + triskelion) recognize the specific plasma membrane proteins (receptors) and bind with them. • After binding with receptors, the specific Form of clathrin molecules causes the plasma membrane to be pinched off from surface and forms a coated spherical cage. This coated vesicle is separated from plasma membrane with the help of a GDP binding protein dynamin. • The clathrin coat of the vesicle is removed by a ATP hydrolyzing enzyme, in order to regain the ability to fuse with the plasma membrane in a new cycle.

Tonsils

Aggregations of nodular and internodular tissue in the walls of the pharynx. Immune system's first line of defense against ingested or inhaled foreign pathogens. three types: 1) palatine tonsils are in the lateral walls of the oral pharynx (near the palate), 2) lingual tonsils are at the base of the tongue, and 3) pharyngeal tonsil (adenoids) is at the roof of the nasopharynx.

Improving Ab: Somatic Hypermutation ($)

Also called affinity maturation. Somatic Hypermutation: Due to AID turning on (via CD40L and CD40R). Cytosine becomes uracil, sloppy repair leads to mismatch (good). Substitution of single-nucleotides at a high rate throughout the rearranged variable region of the heavy and light-chain immunoglobulin genes (V region), selection occurs afterwards so low affinity recombinants die (apoptosis)

Hematopoiesis

All blood cells arise from a single type of stem cell in the bone marrow (a type of CT). This stem cell first gives rise to two lineages; one lineage forms the lymphocytes, and the other lineage forms everything else

Lymph, Innervation/arterial supply of Pharyngeal Constrictors

All constrictors are innervated by the pharyngeal plexus from the pharyngeal branches of CN X, CN IX and sympathetic branches from the superior cervical ganglion Arterial: left thryocervical to inferior thyroid to pharyngeal branch Lymph nodes: 2 Palatine, 1 pharyngeal, 2 tubal and 1 lingual tonsils form the pharyngeal lymphatic or tonsillar ring (Waldeyer's ring) Lymphatic drainage of pharynx is via deep cervical lymph nodes The most important of these are the jugulodigastric which drain the palatine tonsils.

Tetramers

All hemoglobin proteins (should) consist of 2 α-like + 2 β-like subunits if production of one is reduced more than 50% - then surplus of the other type will be seen RBC lifespan is 120 days

Hemoglobin Gene Clusters

All α-like genes in one cluster, all β-like in another (on different chromosomes) Locus control region (LCR) upstream (5') of it all Progression so that more downstream genes are more heavily expressed later in development Expression switch involves epigenetics (methylation) of genes no longer needed

Peyer's patch

An accumulation of lymphatic tissue, aggregated nodules (GALT). The multiple lymphatic nodules are typically found in the ileum. They have germinal centers.

Calcium Release and Contraction (muscle)

An action potential in the sarcolemma travels to transverse tubules. Voltage gated calcium channels (dihydropyridine receptors, DHP, L-type Ca-channels) located in the T-tubule membrane are physically coupled to a calcium channel, the ryanodine receptors (Ry-R) in the membrane of the terminal cisternae of the sarcoplasmic reticulum. These two proteins form the junctional complex which translates the T-tubule membrane depolarization into the release of calcium ions from the sarcoplasmic reticulum. The depolarization produces a conformational change in the DHP receptor and the Ry-R receptor. The Ry-R receptor opens allowing calcium ions inside the sarcoplasmic reticulum to flow through the open Ry-R channel into the cytoplasm of the muscle cell. So, SR-calcium release requires mechanical coupling.

Muscle spindle

An encapsulated sensory receptor (stretch detector, proprioceptor) Composed of highly modified skeletal muscle fibers (intrafusal fibers) located within the muscle near the tendon junctions. Functions when muscle is stretched; detect changes in the length of the muscle fibers; stretch reflex (reflex allows stretched muscle to contract) protect muscle from tearing Extrafusal fibers: innervated by somatic motor fibers

Muscle cell structure

An entire skeletal muscle is made of bundles/fascicles of muscle fibers and is covered by epimysium (dense irregular c.t.) A bundle of muscle fibers is covered by perimysium (dense irregular c.t.) A muscle fiber is a muscle cell; it contains many subunits called myofibrils; each muscle fiber is surrounded by endomysium (loose c.t.) which has fibroblasts and capillaries. A myofibril is a bundle of myofilaments (thick and thin filaments) Myofilaments contain contractile proteins (actin and myosin) Red muscle fiber: high in mitochondria for questions look for peripheral nuclei, myofibrils and succinic dehydrogenase slow but repetitive White muscle fiber: fast but easily fatigured, less mito. than red muscle fiber

Best test for Hematological Disease?

CBC (complete blood count) important components: Hb: O2 carrying capacity. Multiply Hb by 3 for hematocrit Hematocrit and packed cell volume: anemia or not RBC count: INCREASED in primary polycythemia (lymphocytes), secondary polyc. (altitude), and dehydration then follow with reticulocyte count if needed (supravital staining)

Vasculature of the Nasal Cavity (Kisselbach area) ($)

Ant. Ethmoidal a. Post. Ethmoidal a, and Sphenopalatine a Divide into lateral and medial/septal branches Anterior part of the septum is the site of anastomotic arterial plexus involving all 5 arteries supplying the septum (Kiesselbach area)

Pelvic Walls and Floors

Anterior pelvic wall - is formed primarily by the bodies and rami of the pubic bones and the pubic symphysis Lateral pelvic walls - formed by the hip bones and the obturator internus muscles Posterior Pelvic Wall - formed by the sacrum and coccyx, adjacent parts of the ilia, and the S-I joints; piriformis muscle covers the area

Nerves of Cervical Plexus 1

Anterior rami of C1-4: Nerve point Superficial branches are sensory Deep branches are motor (phrenic and ansa cervicalis) Located anteromedialy to levator scapulae and deep to SCM

T cell antigen presentation

Antigen presenting cells (APCs) must hold peptides in MHC I or MHCII which T cells will recognize. B cells don't need MHC though.

Complement system: classical pathway

Antigen-Antibody complement: B's stay, A's leave. IgM is the most efficient activator of the complement pathway, IgG 4 is unable to activate classical pathway. MAC destroys target by making membrane holes Anaphylatoxin (C5a>C3a>C4a) Chemotaxis: (C5a, C3a, C567)

Spleen immune flow

Antigens enter the spleen from the blood (rather than from lymph nodes) and reach the white pulp through the trabecular artery into the central artery and the marginal sinus. APCs in the corona region detect blood-borne antigens that are sampled by PALS-derived T cells. T cells interact with B cells and from this interaction B cells proliferate and differentiate into plasma cells. Plasma cells release immunoglobulins into the blood circulation

Anticoagulants Antithrombin III and Heparin

Antithrombin III (serpin): plasma glycoprotein that can inhibit activity of factors IXa, Xa, XIa, XII, plasmin and kallikrein - thrombin neutralization Heparan sulphate: physiological activator of antithrombin III (improved thrombin-antithrombin interaction) BOTH are anti coagulatins With clotting disorder and low antithrombin III patient won't react to heparin (heparin blocks antithrombin to work)

Isoenzymes

Any one of several different forms in which some enzymes may be found, each having an enzyme specificity but differing in properties such as optimum pH or isoelectric point. Example: Creatine Kinase: Creatine phosphate to creatine (makes ATP) for first seconds of needed energy CK-MM (skeletal muscle) CK-MB (cardiac muscle) CK-BB (brain)

Costocervical Trunk

Arises from the 2nd part of the subclavian a. Usually has 2 branches: Superior/supreme intercostal to the 1st two intercostal spaces Deep cervical, deep cervical muscles May have the dorsal scapular also

Thyrocervical Trunk

Arises just proximal to the anterior scalene Has 4 branches: Inferior thyroid Ascending cervical Suprascapular Transverse cervical

Tongue blood and lymph supply ($)

Arterial: Lingual artery (external carotid), passes deep to hyoglossus Dorsal lingual artery supplies the root, Deep lingual supplies the body Sublingual supplies the floor of the mouth and sublingual gland Venous: collects to IJV Lymphatics: see pic (important)

Laryngeal Muscles and blood supply($)

Arteries Superior laryngeal artery → internal surface of larynx Accompanies the internal laryngeal nerve Inferior laryngeal artery → mucous membrane & muscles in inferior part of larynx Accompanies the recurrent laryngeal nerve Cricothyroid artery → cricothyroid m. Veins laryngeal veins accompany the laryngeal arteries. Superior laryngeal vein → superior thyroid vein → IJV Inferior laryngeal vein → inferior thyroid vein → left brachiocephalic v.

Arteries and Veins of Neck

Arteries: some anatomists like facts others prefer made (up) stories Common carotid artery: Internal carotid External carotid: Superior thyroid, Ascending pharyngeal, Lingual, Facial, Occipital, Posterior auricular, Maxillary, Superficial- temporal Subclavian artery: Vertebral artery and Thyrocervical trunk Veins: they drain, have tributaries not branches, face drained by external jugular, internal parts of skull and deeper neck by internal jugular

Bone Marrow examination

Aspiration (faster, better cytologic details) or biopsy (better architectural details) Indications: weird CBC, iron stores evaluation, evaluation of disseminated infection Site: iliac crest with supine patient

Tongue (development)

At week 4, from arches 1-4 Tongue root: 2 to 4th arch groove has 9th cranial nerve (glassopharyngeal) Anterior 2/3 of tongue: 1st pharyngeal arch

Penis innervation

Autonomic nervous system: with sympathetic (T11-L2) and parasympathetic (S2-S4) fibers (in the pelvis they form the cavernous nerves). Somatic innervation: with sensory and motor (extracorporeal striated muscles) supplies (arrives through the pudendal nerve)

B12 and Folate Metabolism

B 12 needed for function requiring one-carbon metabolism: cell growth/division, esp. blood cells; control of fatty acid synthesis in myelin sheaths of nerves. B12 deficiency causes neuro-problems. R factor in salivary glands will absorb it. Intrinsic factor in the stomach will bind cobalamin. Folate is absorbed by brush-border enterocytes. Some drugs inhibit absorption: phenytoin, alcohol, oral contraceptives. Folate is required for DNA synthesis in reticuloendothelial cells and N-formyl groups Erythrocyte precursors are particularly susceptible to their absence

Antigen processing (B and T cells)

B cell can also be antigen presenting along with functions of antigen recognition and antibody secretion. B cell differentiation occurs in germinal centers.

Adaptive Immunity

B cells use B cell receptors (BCR, immunoglobulin, antibody) and secrete antibodies T cells use T cell receptors and use cytokines and cell surface interactions to help cells and kill infected. Only recognizes peptides

Submental Triangle

Base: hyoid bone Apex: mandibular symphysis Lateral border: anterior digastric Medial border: midline Floor: Mylohyoid Contents: submental lymph nodes and small veins that unite to form the anterior jugular vein The suprahyoid muscles: digastric (anterior belly) and mylohyoid (CN V), stylohyoid (CN VII), and geniohyoid (CN XII)

Anterior Triangle of Neck

Base: margin of the mandible Posterior border:anterior border of SCM Anterior border: midline of the neck Subdivided into four smaller triangles: submental, submandibular, carotid and muscular Nerves: CNX, CNXI, and CNXII

Posterior Triangle

Base: middle 1/3 of clavicle Posterior border: anterior border of trapezius muscles Anterior border: posterior border of the SCM Subdivided into two triangles by the inferior belly of the omohyoid muscle: Supraclavicular and occipital triangles

Cell death via Fas/FasL

Binding of FasL to Fas in cell initiates apoptosis via caspases, a protease. (kills infected cell, un-needed effector T-cells, and self reactive lymphocytes during development)

T-cell education

CFU-L cells go to cortex where they are separated by blood-thymus barrier. Thymocytes are presented to antigens, 95% die by apoptosis, remaining go to medulla graduated: CD4+CD8- Helper T cells CD4-CD8+ Cytotoxic T cells

Bone components

Bone Matrix: Inorganic Component: composed mainly of calcium and phosphorus. Minor elements Mg, Na, K, HCO3, etc are also present. Ca and phosphorus form hydroxyapatite crystals as plates alongside collagen type I fibrils . They are deposited into the gap regions. Ca PO4 is also present in an amorphous form surface crystals form a hydration shell with H2O. This allows ion exchange with extracellular fluid Organic Component: main component is collagen type I (90%) and some collagen type V-matrix also has ground substance in the form of GAGs ( chondroitin sulfate, keratan sulfate and hyaluronic acid) . These form proteoglycans and proteoglycan aggregates. The abundance of coll. I causes matrix to stain acidophilic, whereas cartilage stains basophilic several glycoproteins (osteocalcin, osteonectin,and osteopontin) and sialoproteins are present. They bind to the crystals, fibers, GS and cells . Thus collagen and GS become mineralized to form bone

Submandibular (digastric) Triangle

Bordered by the two heads of the digastric muscle and the margin of the mandible floor: mylohyoid, hyoglossus and the middle constrictor Contents: submandibular gland, facial artery and vein, submandibular lymph nodes (lower face and superficial ear regions) and nerve to the mylohyoid and CNXII

Carotid Triangle

Borders: Omohyoid, posterior digastric and SCM muscles Contents: Carotid sheath (common carotid artery and its two branches, internal jugular vein, CN X), external carotid artery and some of its branches, CN XI & XII, ansa cervicalis, thyroid gland and deep cervical lymph nodes

Muscular Triangle

Borders: Superior belly of omohyoid, anterior border of SCM and midline of the neck Contents: Infrahyoid muscles- omohyoid, sternohyoid, thyrohyoid & sternothyroid. All innervated by the ansa cervicalis (C1-3) except the thyrohyoid (C1 via CNXII) Parathyroid & thyroid gland and thyroid cartilage also located in triangle

Mandibular Depression

Both lateral pterygoids Suprahyoid muscles Infrahyoid muscles Platysma

Cheeks

Boundaries of the cheeks: Oral & mental region, Zygomatic region, Parotid region, Mandible Buccinators : Supplied by the buccal branch of the maxillary artery and the buccal nerve of the mandibular nerve

The Heme group and globin

Each subunit in Hb and Mb contains a heme, protoporphyrin IX, Fe must be in Fe(II) state, Oxygen bound to 6th ligand (out of plane), fifth ligand binds Hist F8, with just heme binding is irreversible. With globin it is reversible and also modulate binding. Solubility and diffusion increase by binding to proteins. O2 binding causes color changes (red in art, purple in veins)

Temporal Region/ Fossa and infratemporal fossa

Boundaries: Superior Temporal line Frontal and zygomatic bones Zygomatic arch Infratemporal crest Fossa: The floor of the fossa is formed by 4 bones that meet at the pterion: frontal, parietal, temporal and greater wing of the sphenoid The middle meningeal artery is located behind the pterion within the middle cranial fossa The roof of the fossa is the temporalis muscle and its surrounding fascia, which also fill the fossa Infratemporal Fossa Contents: Inferior part of temporalis m. Lateral and medial pterygoids Maxillary artery Pterygoid venous plexus V3: mandibular, inferior alveolar, nerve to mylohyoid, lingual, chorda tympani(CN VII), buccal, auriculotemporal nerves Otic ganglion: presynaptic parasympathetic fibers from CN IX. Postsynaptic fibers are secretory to the parotid gland passing through the auriculotemporal nerve

Perineum Muscles

Bulbospongiosus -compress vagina orifice or compress urethra, innervated by perineal nerve, pudenal nerve Ischiocavernosus - maintains erection of penis or clitoris

How do tumors fight hypoxia?

C-myc deregulation causes tumor cells to swell and they get hypoxia. hypoxia causes hypoxic induced factor 1α (HIF-1α) to be stabilized and to turn on a host of genes important for glycolysis and for angiogenesis and to down-regulate oxidative phosphorylation. HIF-1α works with c-myc to create the Warburg Effect (anerobic glycolysis) This only happens in cancer, in normal cells HIF-1a inhibits c-myc. Because the activation of glycolysis in cancer cells is essential to prevent cell death induced by ATP depletion and H2O2 accumulation, the attenuation of glycolysis in cancer cells can induce their death

Easy Cranial Nerves (I, II, III, IV, VI, VIII, XI, XII)

CN I - Olfactory Nerve : Special Visceral Afferent (SVA) CN II - Optic Nerve: Special Somatic Afferent (SSA) -Vision CN III - Oculomotor Nerve has 2 axon modalities: 1-General Somatic Efferent (GSE) 2-General Visceral Efferent (GVE) CN IV - Trochlear- General Somatic Efferent (GSE) *Voluntary motor to superior oblique CN VI - Abducens- General Somatic Efferent (GSE) *Motor to Lateral Rectus CN VIII: Vestibulocochlear- Special Somatic Afferent (SSA) Hearing (Cochlear) Balance & equilibrium (Vestibular) CN XI: Accessory:- Cranial Root (BE/SVE): Axons that are a part of CN X-Innervate muscles of the larynx, pharynx & palate Spinal Root (BE/SVE): -Innervates SCM and Trapezius CN XII: Hypoglossal Axon Modality: GSE *Voluntary motor to muscles of the tongue

Nerves: CN V Nerves: CN VII

CN V3, CN VII, Chorda tympani, Lesser petrosal all can be found in the infratemporal fossa CN V3: Fossa ovale to infratemporal fossa. Branches: auriculotemporal, inferior alveolar, lingual and buccal (sensory not motor) CN V3 supplies also the 4 muscles of mastication but not the buccinator, which is supplied by buccal branch of CN VII CN VII the somatic motor branch to the muscles of facial expression + post. Digastric and stylohyoid Somatic course: Middle cranial fossa -> internal acoustic meatus -> stylomastoid foramen Six branches -> one posterior -> five anterior from the parotid plexus Posterior auricular Temporal Zygomatic Buccal Marginal mandibular Cervical

CO2 and NO2 (heme)

CO2 is a physiological regulator of hemoglobin activity. Nitric oxide (NO) binds to hemoglobin and plays a central role in hemoglobin action and blood pressure control.

Complement receptors and B cell activation

CR1: disrupt immune complex (IC) of RBCs which are sent to liver/spleen. CR2: on B cells can enhance B cell activation (Important) CR3: important for phagocytosis (migration) like CD18 (for cell adhesion) CR1,3-4 stimulates phagocytosis.

Smooth muscle calcium intake and release

Ca++ needed in smooth muscle too. Ca++ from outside and SR. a) Extracellular Ca2+ enters the cell: Calcium coming from the extracellular space enters the cell through voltage-gated or ligand-gated channels. Ca2+ is released from SR in two ways. Binding of chemical stimuli to receptors on the cell membrane causes the intracellular formation of IP3, releasing SR Ca++. Calcium is also released from the SR by a process called Ca-induced calcium release. Calcium entering from the extracellular space opens specific calcium channels in the membrane of the SR allowing calcium to leave (also in cardiac muscle)

Ca2+ concentrations in cytosol, SR and in extracellular fluid

Ca2+ concentration in the cytosol is as low as 10-8 to10-7 mol/L. At this calcium concentration Myosin cannot connect to actin (actin binding sites are covered by tropomyosin) and there is no muscle contraction. Ca++ concentrations in SR and in extracellular fluid is roughly about 10000 times more than Ca++ concentration in Cytosol and a calcium release from SR into the cytosol is required for initiating and producing a muscle contraction.

Cross-bridge cycle (contraction)

Calcium released from the sarcoplasmic reticulum binds to troponin C causing a conformational change in tropomyosin. The movement of tropomyosin uncovers binding sites for myosin on actin (step 1 to 2 in the figure above). Myosin with its incorporated ADP and P binds to actin. This induces a conformational change in myosin causing the release of P and ADP and the rotation of the myosin head (steps 2 to 3 and 4). This rotation is the "power stroke" which pulls the actin containing thin filaments toward the middle of the sarcomere, reducing sarcomere length and producing muscle cell shortening. In the presence of adequate ATP, ATP binds to the myosin head and causes it to dissociate from actin. The binding of ATP and its subsequent conversion to ADP and P causes the myosin head to return to its rest state, ready to bind to another actin and repeat the cycle (steps 4 to 5 and 1). In the absence of ATP myosin will remain bound to actin and the muscle will be in a state of rigor (step 4).

Effector T cells ($)

Change gene expression profiles and gain the capacity to express proteins: CD4 T cells (T helper 1 and 2 cells with MHC II): Cytokines (i.e. IL-4 and IFN-y) Surface molecules (i.e. CD40L and FasL) CD8 T cells (Cytotoxic T cells with MHCI): Cytokines (i.e. IFN-y) Surface molecules (FasL) Cytotoxins - proteins that are used to kill infected cells like granzymes Activation threshold of CD8 MUCH higher than CD4

Lymphoid tissue and lymphocytes

Can exist freely in regular connective tissue (Payer's patches) or surrounded by capsules (like lymph nodes and spleen) 3 types of lymphocytes: 1) B lymphocytes (bone marrow) 2) T lymphocytes (Thymus) 3) NK (natural killer) cells (also present in area are macrophages, dendritic cells etc.) ***B and T cells move around lymph organs (lymphocyte re-circulation) and this is why lymph nodes can change daily

Overview of Lymphatics: Cancer

Cancer spreads by contiguity or by metastasis Metastasis occurs by one of the three ways: 1. Direct seeding of serous membranes of the body 2. Lymphogenous spread (via the lymphatic system) 3. Hematogenous spread (via blood vessels)

Cardiac endocrine cells

Cardiac endocrine cells have secretory vessels (no other cardiac cells do) located primarily in the atrial wall and in the interventricular septum. Produce small peptides hormones (atrial natriuretic polypeptide) Decrease the renal tubules to resorb Na+ and H2O Natriuresis & Diureses down regulate BP(increase Na+ and H2O loss) pic: blue arrow is endocrine cell, orange arrow is mito

Carotid Sinus and Body

Carotid sinus: dilation of internal carotid a. innervated mainly by CN IX and partly X Baroreceptor (pressure) Carotid body: Chemoreceptor innervated mainly by CN IX and partly X. Stimulated by low levels of O2- initiates a reflex which increases rate and depth of respiration, cardiac rate and BP

Veins of scalp and face

Cavernous sinus is main drainage site There are two Sigmoid sinuses that run in the Dura on each side of the head. The Transverse sinus allows drainage of blood from the posterior part of the head and continues on to the Sigmoid sinus, which eventually connects to the Internal jugular vein at the Jugular foramen. The confluence of sinuses is made up of the transverse sinus, superior sagittal sinus, straight sinus as well as the occipital sinus.

Chondrocyte

Cell is actively engaged in synthesis. Note large amt of RER and extensive Golgi. The numerous dark particles in the matrix and territorial matrix contain proteoglycans. From mesenchyme. Appositional growth: Appositional growth occurs due to the presence of a perichondrium where chondrogenic cells become chondroblasts increasing the width of the cartilage model

Static of pelvis

Center of gravity passes through: atlantooccipital joint lower lumbar vertebrae, anterior to promontory head of femur - acetabulum talus (highest point of longitudinal lantar arch) only possible if the superior aperture of pelvis is bent 60- 65 degrees - Pelvic inclination (Ant. Sup iliac Spine and symphysis lies approximately in the same frontal plane). Rotation axis of sacroiliac joint is posterior to body weight.

Central/ Peripheral B cell tolerance ($)

Central tolerance (in bone marrow) occurs during Ab production, B cells with no self reaction migrate to periphery (lymph tissue) where they experience chemokines. Multivalent self antigen gives B cell one more chance to rearrange or apoptosis/clonal deletion occurs. Soluble self-antigen leads to anergic (incapable of activation) B cells.

Cytokines

Characteristics: not preformed or stored: produced de novo, short half life, different cells may produce the same cytokine, regulate cell activation, proliferation, and differentiation, control inflammation: pro /anti inflammatory Pleiotropism: same cytokine may exhibit, different biological properties Redudancy: different cytokines may exhibit the same biological activity Additive/Antagonistic: a cytokine may affect the function of another cytokine

Cartilage Cells

Chondrocytes sit in lacunae- are distributed singly or in clusters called isogenous groups: have well dev RER and Golgi, produce collagen II, GAGs, proteoglycans and adhesive glycoproteins. Chondrocyte function depends on GH (somatotropin), thyroxine & testosterone. These increase syn of sulfated GAGs. Decrease syn of these GAGs is carried out by cortisol, cortisone & estradiol. Cartilage Growth depends mainly on GH. GH does not act directly on cartilage cells but via somatomedin C (insulin-like growth factor) from the liver.

Vitamin K in Blood Coagulation

Cofactor of the enzyme GGC which activates coagulation factors II, VII, IX, X (enables Ca++ binding) Also promotes gamma carboxylation of proteins C, S Epoxide form of Vit.K is inactive (via gamma carboxylation process) activated again by VKOR, hydroquinone form of Vit. K Calcium chelators: inhibit thenase/prothrombinase complexes

Fibrocartilage

Combination of dense CT (col I) and hyaline (col II) No perichondrium - is a combination of dense regular C.T. and hyaline cartilage - is predominantly composed of coll type I - thus displays acidophilic properties - chondrocytes are dispersed singly, in rows, and in isogenous groups surrounded by scant amount of ground substance Location : intervertebral disc, symphysis pubis, menisci of knee joint - located in areas where support and tensile strength are required.

Dermis and skin blood supply

Composed of dense, irregular connective tissue that contains many type I collagen fibers and networks of thick elastic fibers Divided into a superficial papillary layer and a deeper reticular layer Blood supply: dermal papillus contains capillaries When arteriovenous anastamoses are open and metarteriole sphincters closer to epidermis are closed, diverts blood from outer part of body (keeps body warm)

Medulla (of lymph nodes)

Composed of medullary sinuses & medullary cords (lymphocytes, macrophages and 10% of plasma cells) enmeshed in reticular fibers and cells. Plasma cells that come from outer cortex migrate to bone marrow where they secrete antibodies. Medullary sinuses contain lymph, lymphocytes, macrophages (and granulocytes if the lymph node is draining) Medullary chords have plasma and B cells.

Cartilage

Composition : Cells & Extracellular matrix (ECM) ECM - fibers & amorphous ground substance(GS) GS - glycosaminoglycans, proteoglycans and chondronectin (glycoproteins) Location: 1. Ends of long bones and ventral end of ribs 2. Surfaces of joints 3. Respiratory system and external ear 4. Epiphyseal plates for growth of long bones Cartilage stains basophilic (purple), bone stains acidophilic (pink)! Functions: 1. Support of soft tissues 2. As a shock absorber (resist compression) 3. Free - sliding surface for joints ( smooth surface) 4. As a template for growth of long bones Main Features of Cartilage 1. Hard consistency - proteoglycans &collagen 2. Avascular, lack of nerves & no lymphatics 3.Surrounded by a perichondrium except articular cartilage and fibrocartilage

Calcium Uptake and Relaxation (from contraction)

Cytoplasmic calcium must be reduced to stop contraction. The calcium pump (Ca-ATPase) located in sarcoplasmic recticulum membrane moves calcium ions from the cytoplasm of the muscle cell into the sarcoplasmic reticulum. To further increase the amount of calcium sequestered, the sarcoplasmic reticulum contains a calcium binding protein called, calsequestrin.

Pterygopalatine Fossa ($)

Contents: Terminal part of the maxillary artery and its branches Pterygoid venous plexus Maxillary nerve (CN V2) and associated pterygopalatine ganglion Branches of the ganglion are considered to be branches of the maxillary nerve Neurovascular sheaths of the vessels and nerves Fat filling empty space Pterygopalatine Ganglion: ganglionic branches connected morphologically not functionally (sensory branches of CN V2), convey PNS Ganglionic branches Greater & Lesser palatine Orbital Nasopalatine Posterior superior nasal branch Pharyngeal Path: Greater petrosal branch of CN VII then in the nerve of the pterygoid canal after it has joined the deep petrosal nerve Postganglionic parasympathetic fibers leave the ganglion along zygomatic and zygomaticotemporal branches of CN V2 to the lacrimal gland

Occipital Triangle

Contents: Occipital artery, CNXI, Nerve point, Nerves to the muscles of the floor, transverse cervical artery Floor: Spenius capitis, levator scapulae, anterior and middle scalene

B cell subsets

Conventional mature B (2) cells CD5- : • Mature B cells • More diverse repertoire • Respond to T-dependent antigens • Require T cell help B (1) cells CD5+/CD5- • Majority of B cells found in fetus and neonate • Restricted repertoire Reactive towards bacterial antigenicity, can cross-react with multiple antigens preferentially to TI antigens • Provide protection in early life before adult repertoire develops

Regional body temperatures

Core temperature constant (75% heat production BMR) Foot and Head can drastically alter temp. Mean TSkin :~ 34°C (by a naked person in a neutral thermal environment) Mean body temperature (Tb) : Averaged from meanTSkin and TCore Location for measurement of Tb: Rectal better than Oral better than Axillar

Iron Homeostasis

Correlation between marrow iron and blood ferritin

Antigen recognition site

Created through gene rearrangements controlled by RAG 1 and RAG 2 (along with beta receptors and TCRs). V region of Ab are hypervariable (HV) causing binding site changes, HV = CDR (hotstops) main determinant of specificity.

Anterior cranial fossa

Cribriform plate (foramina): CN I

Fascia and Pouches of Urogenital Triangle

Deep to superficial: Superior Fascia of Pelvic Diaphragm (Pelvic diaphragm) Inferior Fascia of Pelvic Diaphragm (Deep Perineal Pouch) Perineal Membrane (Superficial Perineal Pouch) Perineal/ Colles fascia (Subcutaneous tissue) Skin

Control of smooth muscle contraction

Determined by the balance between the enzyme activities of MLCK and MLCP 1. reduce Ca++, MLCP favored, dephos. causes relaxation 2. cAMP lowers affinity of Ca++ to MLCK, relaxation favored 3. NO activated MLCP 4. PKC inc. actin availability leading to more contraction

Improving Ab: Isotype (class) switch

Determined by what cytokine stimulates the B cell Alters the isotype of Ig expressed by B cell in the constant region Segments of the gene encoding the constant region are cleaved and rejoined. Antibody specificity remains the same. Switches are via introns and all are productive. IFN-y in (from T cell) lymph node to IgG TGF beta -gut mucosa (MALT) IL-4 IgE allergies

Cranial Meninges and venous sinus

Dura mater , Arachnoid mater , Pia mater Main sinus: Cavernous sinus in mid brain (contains oculomotor nerve, trochlear nerve, ophthalmic nerve, maxillary nerve) and confluence of sinuses in back Dura mater attaches to Crista Gali

Serum Electrophoresis ($)

Different protein stains, albumin negative (closest to anode) and in greatest abundance. Use serum since fibrinogen skews beta area. a-1 band has a-1 antitrypsin, a-2 globulin region has a-2 macroglobulin (renal diseases) y-globulins: chronic infection if dark and thick banded

Rhesus Blood Group

Differs in presence (Rh+) or absence (Rh-, autosomal recessive) of the rhesus antigen (protein) Determined by presence or absence of polypeptide D (different amino acid variants in the polypeptide explain subgroups of Rh+) 15% of North Americans are Rh- (variation between populations) No antibodies against Rh+ in Rh- people (different from the situation in ABO blood group system)

Immunogenicity factors

Dose: small quantities rapidly cleared while large amounts provoke response (if large amount inhibits response you get anergy) Route: most antigens enter mucosa where gut will digest/destroy them, those entering bloodstream remain intact and more likely to trigger immune response Adjuvants: chemical substances that enhance the immune response to an antigen by prolonging the persistence of the antigen (small amounts over a long time), stimulating or modulating immune cells (antigen becomes immunogen), or enhancing macrophage function

B cell development ($)

Early/Late pro-B cell uses RAG 1 and RAG 2 to rearrange heavy chain D-J and V-DJ (then RAG 1 and 2 get down-regulated). Heavy chain made first. Large pre-B cell: surrogate light chain with heavy chain (reactivate RAG 1 and RAG 2) to form pre-B receptor (or apoptosis occurs). Pro-B cell to Pre-B cell needs Ig (alpha) and Ig(beta) with CD19 for signaling. After light chain arrangement it becomes an immature B cell, expression of IgM but needs IgD. Mature when it has IgM and IgD During light chain development only one allele should be made (or cell becomes anergic). Second round of possible apoptosis. Mature B cell is naive/virgin until meeting first antigen. One of the earliest markers that always stays with development is CD 19 (signaling).

Temporomandibular Joint (TMJ)

Elevation, depression, gliding and rotation/pivoting Joint involves:Auricular tubercle, Mandibular fossa, Head of mandible Protrusion and retrusion (gliding) occur between the temporal bone and the articular disk, (sup. cavity) The hinge and rotation/pivoting movements occur in the inferior cavity Lateral ligament is a thickening of the capsule which strengthens the joint laterally. Helps prevent posterior dislocation Stylomandibular ligament is a thickening of the parotid capsule. Does not significantly strengthen the TMJ Sphenomandibular ligament is the primary passive support of the mandible. Acts as a fulcrum

Heme catabolism

Elimination through the bile requires enzymes in different parts of the body. Interruption of bilirubin results in jaundice: a result of liver disease, but hemolytic disorders also. Evaluation of sclera for discoloration and the underside of the tongue performed. Neonatal jaundice presents: condition of undeveloped liver function in.

CN IX Glossopharyngeal Nerve Pathway

Emerges from the brainstem in the lateral medulla and exits the posterior cranial fossa through the jugular foramen. *SVE axons innervate stylopharyngeus. SVA axons carry taste perception from the posterior 1/3 of the tongue. GVE axons innervate the parotid gland. GVA axons run on the lingual nerve of IX, carotid nerve and tympanic nerve *Tympanic nerve branches from CN IX and enters middle ear via the tympanic canaliculus. *Sensory (GVA & GSA) axons form tympanic plexus within middle ear *Parasympathetic (GVE) axons emerge as the lesser petrosal nerve from the tympanic plexus and lesser petrosal hiatus. *Lesser petrosal nerve then leaves the cranium through foramen ovale. *Preganglionic parasympathetics synapse in the otic ganglion, and go to the parotid gland via the auriculotemporal nerve (V3) BE/SVE: Stylophyarngeus muscle SVA axons (taste) from the posterior 1/3rd of the tongue GVE axons to the parotid gland GVA axons from the mucosa of tonsils, pharnyx for afferent part of the gag reflex

Pelvic Cavity

Enclosed by bony, ligamentous and muscular wall. Contains the urinary bladder, ureters, pelvic genital organs, rectum, blood vessels, lymphatics and nerves

Spleen anatomy 1

Enclosed by dense connective tissue capsule from which trabeculae extend into the parenchyma of the organ Large trabeculae originate at the hilum and carry nerves and arteries into the splenic pulp and veins out of it The splenic pulp has two components, red pulp and white pulp. White pulp is an important production site of lymphocytes, which then migrate to the red pulp and enter the circulation. The red pulp makes up the 75% of the spleen and contains all of the formed elements of blood. Consists of blood-filled sinusoids separated by splenic cords of Bilroth which have reticular tissue

Limb development (embryology)

End of week 4, limb buds become visible as outpocketings from the ventrolateral body wall; hindlimbs develop 1-2 days later than the forelimbs; Positioning of the limbs is regulated byHOX genes. Mesenchymal core is derived from somatic/ parietal layer of the lateral plate mesoderm (forms bone and connective tissue of limbs) In week 6, hand and foot plates occur at the terminal portion of the limb buds; later, fingers and toes are formed when cell death in the AER separate this ridge into five parts. CLINICAL: thalidomide inhibited AER (no arm/leg development; flipper babies)

MAC (Terminal/membrane Attack Complex) ($)

End result of all complement pathways. When terminal components aggregate: formation of a membrane hole lysing target EXAM QUESTION: Innocent bystander effect: MAC inhibition by CD59 'Homologous Restriction Factor' which prevents C9 from completing the hole. Without it, own cells are lysed

Viscera of Neck (3 layers)

Endocrine : thyroid & parathyroid glands. Respiratory : larynx & trachea. Alimentary : pharynx & esophagus.

Phases of antigen elimination

Equilibrium phase: distribution of antigen between vascular and the extravascular compartments Catabolic Decay phase: antigen destruction by innate cells, processing, and presenting. Antibody production at point C. Immune Elimination phase: formation of Ab-Antigen immune complex (so you can't see sole antibodies since they are bound) Last phase: you can see sole antibodies Process takes ~10-14 days

Overview of Lymphatics: Drainage of the Pelvis ($$$)

Ex. Iliac nodes: above pelvic brim, lymph from: inguinal nodes, deep lymphatics of the abdominal wall below the umbilicus, adductor region of the thigh, some pelvic viscera. Drain then to common iliac nodes. Internal Iliac Nodes: near int. iliac and sup/ gluteal arteries. Drainage from: inferior pelvic viscera and glut. region. Drain to common nodes. Sacral nodes: receive lymph from the posteroinferior pelvic viscera (inferior parts of rectum and vagina and posterior pelvic wall) and drain either into:Internal iliac nodes or Common iliac nodes Common iliac nodes to lumbar/ caval/ aortic nodes

Cardiac conducting cells

Exhibit inherent and spontaneous rhythmic contraction. Heart beat is initiated, regulated and coordinated by cardiac conducting cells. Nodes (SA, AV) and fibers (bundle of His, Purkinje fibers) Sympathetic and parasympathetic fibers that terminate at nodes only modify the rate of intrinsic cardiac muscle contraction.

Sympathetic Trunk

Extends superiorly to the base of the skull Has three cervical ganglia: superior, middle and inferior Ganglia receive sympathetic input from the superior thoracic spinal nerves and their white rami communicantes Postsynaptic neurons send fibers to: Cervical spinal nerves (gray rami communicantes) Thoracic viscera (cardiopulmonary splanchnic nerves) Head and neck viscera (sympathetic periarterial plexus/carotid plexus)

Veins of the Root of the Neck

External Jugular Vein (EVJ): drains primarily the face and scalp Internal Jugular Vein (IVJ) starts at the jugular foramen, draining the brain, internal skull and deep neck structures

General Ear gross anatomy

External and middle are mainly concerned with the transference of sound to the internal ear Internal ear contains the organs for equilibrium and hearing The tympanic membrane separates the external and middle ear The pharyngotympanic tube connects the middle ear to the nasopharynx

Thyroid gland/ Parathyroid glands

External carotid → Superior thyroid artery (supply anterosuperior aspect) Subclavian → Thyrocervical trunks → Inferior thyroid artery (supply posteroinferior aspect) superior poles → Superior thyroid veins (accompany sup. thyroid artery) middle of lobes → Middle thyroid veins (accompany inf. thyroid artery) inferior poles → Inferior thyroid vein Parathyroid glands: Parathyroid veins drain into the thyroid plexus of veins Lymphatic vessels drain into deep cervical lymph nodes and paratracheal lymph nodes The nerve supply is from thyroid branches of the cervical sympathetic ganglia

Iron states

Fe(II) is the reduced form and ferrous Fe(III) is the oxidated form and ferric Iron carrier in blood is the protein transferrin Excess iron store inside cells is with the protein ferritin (also hemosiderin) Iron bound-O2 transport is by proteins myoglobin and hemoglobin

Pathophysiology of Neuromuscular signal transmission

For muscle relaxation during surgical operations: a) Acetylcholine antagonists (group 4; d-Tubocurarine): These drugs competitively bind with ACh receptors but can not open the channel to produce an end plate potential. b) Acetylcholinesterase inhibitors (group 6) prevents the break down of Ach and therefore Ach remains bound on its receptors. As a result the cation channels remain open and produce a permanent end plate potential, which keeps the plasma membrane depolarized. A second action potential can not be produced, because voltage gated Na+ channels are in a refractory state and the removal of this state requires a repolarization of the membrane.

Face (development)

Formation starts at end of 4th week Top to bottom: nasal placode, frontal nasal prominence, maxillary prominence, mandibular arch, 2nd and 3rd pharyngeal arches. Nasolacrimal groove develops between the Maxillary and Lateral nasal prominences , forming the Nasolacrimal Duct Oblique facial cleft: lateral nasal prominence and the maxillary prominence misjoining

Tongue anatomy and innervation ($)

Formed by somites. Divided into anterior 2/3rd and posterior 1/3rd by a V-shaped sulcus terminalis Foramen cecum, an embryological remnant, marks the site of the thyroglossal duct (thyroid gland) Ventral tongue: Lateral to the frenulum, the deep lingual vein can be seen through the mucosa, lateral to the lingual vein, a fold of mucosa forms the plica fimbriata Tongue Movements: Protrusion: Genioglossus on both sides Retraction: Styloglossus and hyoglossus on both sides Depression: Hyoglossus and genioglossus on both sides Elevation: Styloglossus and palatoglossus on both sides Motor Innervation: Hypoglossal nerve (CN XII) except the palatoglossus (CN X) Sensory Innervation: Anterior 2/3rd: GSA: Lingual nerve of Vagus taste: Chorda tympani Posterior 1/3rd: Glossopharyngeal nerve Base: Internal laryngeal nerve

Pelvic Floor

Formed by the funnel shaped pelvic diaphragm - consists of the levator ani and coccygeus muscles and their fascia. Stretches between the pubis anteriorly and the coccyx posteriorly and from one lateral pelvic wall to the other. Levator Ani: Innervated by the nerve to levator ani from S4 and the inferior anal (rectal) nerve (from S2-S4) and the coccygeal plexus

Follicular Dendritic Cell (FDC)

Found in germinal centers (GC),are non-migratory and capture antigens; can retain these antigens for years FDCs form a network that attracts and organizes lymphoid cells To become selected as a future memory cell, a GC B cell must bind the antigen on the FDCs, otherwise they enter apoptosis. Follicular dendritic cells are NOT antigen-presenting cells because they lack MHC II molecules They are a different cell type than dendritic cells, which are APCs They are also not reticular cells.

Histology of Compact bone

Four lamellar systems: 1. Outer circumferential lamellae beneath periosteum (outer layer of dense fibrous tissue) 2. Osteons ( Haversian systems ) -bulk of compact bone is made of osteons 3. Interstitial lamellae - remnants of osteons 4. Inner circumferential lamellae - encircles marrow cavity. Not as thick as outer C.L.

Pterion

Fracture of it leads to headache, vision problems, disorientation etc. Associates with epidural hematoma Joining of frontal, parietal, temporal and sphenoid (houses superior orbital fissure, foramen rotundum, and foramen spinsoum) bones Also has middle meningeal artery which goes through foramen spinosum

Facial branches of CN 7

From top of eyebrow to lateral neck (top to bottom): temporal, zygomatic, buccal, marginal mandibular, cervical Trigeminal Nerve (V) has V1-V3 which is ophthalmic, maxillary, and mandibular. Also lacrimal, frontal, and supra orbital nerves in eye Annulus Tendineus: common origin of rectus eye muscles Short ciliary nerve carries parasympathetic fibers from CN III to the Ciliaris muscle and Sphincter Pupillae muscle

Paranasal Sinuses

Frontal: Contained within the frontal bone are innervated by branches of the supraorbital nerve (CN V1) Ethmoidal: Anterior cells drain into the Hiatus semilunaris Middle cells drain into the ethmoidal bulla Posterior cells drain into the superior meatus Sphenoid: Drains into the Spheno-ethmoidal recess Posterior ethmoidal nerves and arteries supply them Maxillary: largest of paranasal sinuses Arterial supply: mainly superior alveolar artery, but also descending and greater palatine arteries Innervated by the anterior, middle and posterior alveolar nerves from CN V2

White blood cells/leukocytes

Function in tissues not blood (part of CT). Leave the bloodstream by migrating between endothelial cells of the blood vessels: diapedesis. Types of leukocytes: granulocytes: neutrophils, eosinophils, basophils, agranulocytes (live longer): monocytes, lymphocytes. But all WBCs have azurophilic granules (lysosomes). Most abundant: neutrophils and lymphocytes

Spleen functions

Functions 1) Secondary lymphoid organ; lymphocytes respond to blood-borne antigens by initiating an immune reaction that activate T cells and B cells: for antibodies and activated lymphocytes that are delivered to the blood 2) Filters blood by clearing particulate matter, infectious organisms, and aged or defective RBCs and platelets (also recycles iron) 3) During early fetal development, it is temporarily an organ of hematopoeisis Accounts for ~25% of lymphocytes Major repository of mononuclear phagocytic cells Stores ~1/3 of body's platelets

Ligaments of Penis

Fundiform ligament: condensation of collagen and elastic fibers of the subcutaneous tissue that descends in the midline from the linea alba anterior to the pubic symphysis, splits to surround the penis and then unites and blends inferiorly with the dartos fascia forming scrotal septum. Suspensory ligament: condensation of deep fascia that arises from the anterior surface of the pubic symphysis, splits to form a sling that is attached to the deep fascia of the penis at the junction of its root and body.

Nerve Fiber Modalities / Types

GSE: (General Somatic Efferent): motor fibers to skeletal, voluntary musculature GSA: (General Somatic Afferent): fibers that carry general sensation (touch, pressure, pain & temp) GVE: (General Visceral Efferent): motor fibers to smooth muscle, glands, viscera GVA: (General Visceral Afferent): fibers that carry visceral sensation BE/SVE: (Branchial Efferent/Special Visceral Efferent): motor fibers to skeletal, voluntary muscles that developed from branchial (pharyngeal) arches SVA: (Special Visceral Afferent): taste & smell SSA: (Special Somatic Afferent): vision & hearing

Mutations Convert Proto-Oncogenes into Oncogenes

Gain of function mutations: Point mutations (const. active gene product) Gene amplication (over expression of product) Chromosomal translocation (growth-regulatory gene under the control of a different promoter and that causes inappropriate expression of the gene) Loss of function mutations in tumor suppressor genes: p16 cyclin-kinase inhibitor (inhibit progression through cell cycle) Receptors for secreted hormones: TGF-Beta) inhibit cell proliferation Checkpoint-control proteins Proteins that promote apoptosis Enzymes that participate in DNA repair

Albumin in blood vessels

Uses albumin in vessels to keep water in (away from interstitial placces). Edema in hypoalbuminemia

Class I MHC overview

Genes: HLA-A, HLA-B & HLA-C (polymorphic) Structure:heavy chain a subunit (a1,a2, and a3 variable ) and a b2 microglobulin (same for everyone) Located: on all nucleated somatic cells Function: presents foreign antigen (intracellular) in peptide form (shorter than MHCII) to CD8 displaying T cells. Ligand-Receptor interactions: T cell receptor, CD8, CD3 & CD28 on the surface of the CD8+T cell with MHC-I & CD80/86

Class II MHC

Genes: HLA-DA, HLA-DB & HLA-DC Structure:heavy chain a subunit (a1,a2) and b subunit (b1 and b2) Located: Dendritic cells, macrophages, B lymphocytes & thymic stromal cells Function: Present foreign antigenic peptides (longer) derived from organisms captured outside of the APC to CD4+T cells, promotion of naïve CD4+T cells to T helpers, macrophage activation and activation of B cells and class switching Ligand-Receptor interactions: MHC-II & CD80/CD86 on the surface of the Ag presenting cell with T cell receptor, CD4, CD3 & CD28 on the surface of the CD4+ T cell (for B cells and macrophage) MHC-II & CD40 with T cell components

Tumor cells sustain TCA cycle activity and produce NADPH during proliferation (via ME and Glutamine) ($)

Gets rid of NADH so glycolysis keeps moving and to generate NADPH so fatty acid and nucleotide synthesis continues. Tumor cells use glutamine to turn citrate and malate into lactate (making the needed NADPH) Malic enzyme needed! Lactate, alanine and NH4+ are secreted by the tumor. (main nutrients needed are glucose and glutamine)

Biochemical changes in cancer cells

Glycolysis increases Oxidative phosphorylation decreases The pentose phosphate pathway switches from the oxidative to the non-oxidative pathway The cell becomes glutamine "addicted" De novo fatty acid synthesis increases De novo nucleotide synthesis increases Anti-oxidative enzymes are up-regulated

Bone classification (two ways)

Gross observation of bone: Organized in 2 ways 1. Spongy bone - with numerous interconnecting cavities & osseous projections (trabeculae). Matrix has irregular arrangements of lamellae . Hence called spongy, trabecular or cancellous bone 2. Compact bone - solid mass with few intervening spaces. Compact bone forms rigid outer shell which resists deformation, whereas Spongy bone forms internal struts. Maturity of bone: 1.Primary bone ( immature or woven bone) - first bone to form -fetal dev and in bone repair. - abundant osteocytes and haphazard organization of collagen fibers (weak bone) and low mineral content. This bone is remodeled and replaced by secondary bone except in tooth sockets , suture lines in skull,and insertion sites of tendons. 2. Secondary bone (mature or lamellar bone) -found in adults. This replaces primary bone. - composed of parallel or concentric lamellae of collagen. - matrix is calcified (strong bone).

Nasal conchae

Increase surface area for heat exchange 5 passages: Spheno-ethmoidal recess, 3 lateral meatuses and 1 common medial nasal meatus Inferior conchae: longest and broadest and is an independent bone. The middle and inferior conchae are medial processes of the ethmoid bone. When infected/irritated the mucosa may swell rapidly, blocking the nasal passage

Allosteric Effectors of Hb

H+: Lower pH favors the T state which causes Hb to release bound O2. This is known as the Bohr Effect. CO2. Release of CO2 lowers pH via conversion to HCO3, reinforces Bohr Effect. Bisphosphoglycerate (BPG): regulation of activity via binding more strongly to T state, helps to release O2. BPG binds to hemoglobin and decreases the oxygen affinity and keeps it in the deoxy form Lower pH leads to shift of curve to right leading to release of O2 (negative allosteric regulation) Cl- and increased temp also shift right.

Neutrophil Oxidative Burst

H2O2 used by myeloperoxidase (MPO) plus Cl- to form HOCl produces: the strongly antiseptic hypochlorite ion (OCl-) which is the active ingredient in bleach which denatures proteins and membranes of microorganisms. The burst releases primary granules.

Haptoglobin and Hemopexin

Haptoglobin binds ab dimers (from Hb) to mononuclear phagocyte system out of body, low haptoglobin levels hint at internal bleeding hemopexin binds ferric iron to liver and out of body

NK (Natural Killer) cell (Innate defense)

Has killer activating receptor and killer inhibitory receptor MHC class I molecule is on bodies cells which binds to inhibitory receptor (no attack) If no MHC I present then perforins and granzymes released which kills the other cell

Lymphocyte development

Hematopoetic stem cells may become Myeloid stem cell CFU-GEMM or CFU-CL, the latter forms lymphocytes: if they migrate to thymus they are T lymphocytes while others become B lymphocytes in bone marrow

Erythropoiesis 1 (CFU-GEMM to orthochromatophilic erythroblast)

Hematopoetic stem cells may become Myeloid stem cell CFU-GEMM then become CFU-E. The cell gets smaller, the organelles are shredded and Hb is gained, bloodstream release in 7 days 1. Proerythroblast -large cell, basophilic cytoplasm,visible nucleoli 2. Basophilic erythroblast -strongly basophilic cytoplasm, no visible nucleoli. Basophilia caused by the large number of polyribosomes involved in the synthesis of Hb. 3. Polychromatophilic erythroblast -During this stage, polyribosomes decrease, and areas of cytoplasm begin to be filled with hemoglobin which is acidophilic: cell stains both colors (basophilic and acidophilic) 4. Orthochromatophilic erythroblast -Nucleus continues to condense, lose evident basophilia (not all polyribosomes) resulting in uniform acidophilia

Iron Uptake in the digestive system

Heme-iron transfer is faster but Fe(II) transfer via DMT1 occurs more uptake in duodenum, vit C helps, excess stored in ferritin, ferriportin protein controls the amount of iron delivered to the blood protein transferrrin. Free iron causes membrane damage.

Stress and Immunity

High stress leads to decreased immunity and vice versa. Also, infection is the presence of pathogens, disease is the deviation from normal structure and function, and immunity is protection from infection and restoration of normal function and structure

Immunity (two types)

Humoral via antibodies and Cell-mediated by cells

Blood Pressure/Hydrostatic pressure

Hydrostatic pressure is the pressure exerted by a fluid at equilibrium due to the force of gravity Osmotic pressure is due mainly to plasma proteins Capillaries are leaky; when blood enters capillary a lot of fluid gushes out, most fluid is reabsorbed further "downstream' back into the capillaries (blood), what isn't absorbed becomes lymph (10%)

Growth and regulation of Cardiac muscle

Hypertrophy No regenerative capacity, dead muscle cells are replaced by connective tissue

Growth/ Regeneration of Skeletal Muscle

Hypertrophy: increase the volume of the fiber. (opposite is Atrophy) Regeneration: can be regenerated if the external lamina and the satellite cells are intact.

How to kill cancer cells (4)

Induce necrosis by depleting the cell's ATP: inhibit HK2. Induce apoptosis: cause the Apoptosis Inducing Factor (AIF) to be released from the mitochondria by covalently altering HK2 so it cannot bind to VDAC Decrease the pH within the cell inhibit the release of the H+ ions generated by the cancer cell: inhibit the production and release of lactate. Increase the reactive oxygen species within the cancer: turn on oxidative phosphorylation (OX-PHOS) by allowing more pyruvate to enter the mitochondria

Idiotypes, Isotypes, and Igs of Antibodies

Idiotypic variation - variations in variable region, particularly hypervariable region Isotypic variation: variations in the function of Ab Isotypes: IgM: first Ab secreted, found on naive B cells, is a pentamer, activates classical complement, only found in blood IgG: second Ab secreted, most abundant Ab in blood/lymph, monomer, opsonization, neutralization and complement functions IgA: monomor or dimer (J chain with secretory ability), most prominent in gut and saliva, neutralization function IgE: monomor, degranulation function, high affinity to Fce receptors of basophil, eosinophils and mast cells (ALLERGY/PARASITES) Chronic disease IgG elevated, if new IgM elevated

Epithelial Reticular Cells (ERCs)

In cortex and medulla of thymus. They provide a meshwork for thymocytes and a cytorecticulum structural support. In every other cell reticular cells from fibroblasts do this. Connected by desmosomes and have keratin Int. filaments. Secrete thymic hormones and form blood-thymus barrier

Superficial perineal pouch

In males: Root (bulb and crura) of the penis, Bulbous urethra In females: Clitoris, Bulbs of the vestibule, Greater vestibular glands both: Ischiocavernosus, Bulbospongiosus, Superficial transverse perineal muscles, deep perineal branches of the internal pudendal vessels and pudendal nerves.

Deep perineal pouch

In males:Intermediate urethra, Deep transverse perineal muscles, Bulbourethral glands, Dorsal neurovascular and structures of the penis In females: Proximal part of the urethra, A mass of smooth muscle in the place of deep transverse perineal muscles, Dorsal neurovasculature of the clitoris. both: Urethra, external urethral sphincter

Class I MHC process ($)

In some cell proteasome (degrades proteins) picks up proteins of pathogen, proteins cleaved in channel and recycled or picked up by transporters in ER to TAP-1/TAP-2 which loads up and sends to Golgi where it gets translocated to surface of the cell, some CD8 cell hooks up to MHC 1 being presented and releases granzymes, killing the presenting cell proteasomes may become immunoproteasomes during inflammation which are better at cleaving and producing peptides

Lactate Dehydrogenase

LDH1: MI (also for myocardial infarction docs use troponin due to sensitivity and specificty) LDH5: hepatitis

Perineum

Inferior to the pelvic outlet and is separated from the pelvic cavity by the pelvic diaphragm (Levator ani and coccygeus muscles) Boundries: Anteriorly by pubic symphysis; Anterolaterally by inferior pubic rami and ischial rami; laterally by ischial tuberosity; Posterolaterally by sacrotuberous ligament; inferiorly by sacrum and coccyx Two Triangles: Anal triangle (posterior) contains the anus and the Urogenital triangle (anterior) contains the root of the scrotum and penis in males or the external genitalia in females

Intrinsic Pathway

Initiation by blood contact (neg. charged surfaces, thrombin, and collagen) Thrombin plus damaged surface contact leads to: Activation of inactive factor XII into active XIIa (facilitated by kininogen/kallikrein) XIIa catalyses the activation of XI into XIa XIa catalyses conversion of inactive factor IX into IXa (Ca+2 dependent step) IXa and factor VIIIa in presence of Ca+2 binds to the membrane phospholipids of aggregated platelets to form the tenase complex (important) Binding of inactive factor X to tenase complex activates it into Xa (amplifying production of Xa)

Types of Immune Responses ($)

Innate: Non-specific recognition of antigens, fast, and short-lived ex) Natural Barriers, Phagocytes, Dendritic cells, Neutrophils, Macrophages, Mast cells,Eosinophils, Basophils, Complements Adaptive: specific antigen recognition, slow, long-lived (second response better) ex) B and T cells

RBC membrane

Integral membrane proteins with two main types: glycophorins and band 3 proteins. Carbohydrate groups on glycophorins and band 3 proteins, and glycolipids form the ABO blood group antigens. The band 3 protein is an ion transporter of bicarbonate.

Palate (development)

Intermaxillay segment gives rise to: 1. Philtrum of the upper lip 2. The median part of the maxillary bone with its four incisor teeth 3. Triangular primary palate Secondary palate is formed by outgrowths from the maxillary or palatine shelves.

Posterior cranial fossa

Internal acoustic meatus: CN VIII and CN VII Jugular foramen: CN IX-X-XI and Sigmoid sinus -> Internal jugular vein Hypoglossal canal: CN XII

Piriform Recess and Vallecula ($)

Internal and recurrent laryngeal nerves lie deep to the mucus membranes Vulnerable to injury when foreign bodies lodge in the recess or during thyroidectomies Recurrent laryngeal nerve supplies all the muscles of the larynx as well as mucus membranes below the true vocal cords

Calcium Uptake and Relaxation

Intracellular calcium concentration is reduced by active uptake of calcium into the SR as well as by active extrusion of Ca from the cell by cell membrane calcium pumps Na+/Ca2+-antiporter and Ca2+/H+-antiporter.

Tertiary Hemostasis

Involves clot retraction (prevent further hemmorhage) and fibrinolysis (plasmin mediated clot breakdown) Conversion of inactive plasminogen (liver) into active PLASMIN is promoted by 1. Tissue plasminogen activator (tPA)-a few days after injury 2. Urokinase Plasmin is eventually inactivated by α2 antiplasmin/α2 macroglobulin

Secondary Hemostasis

Involves extrinsic and intrinsic coagulation cascades (formation of fibrin meshwork around the plug.) Extrinsic pathway initiates the generation of active factor Xa Intrinsic pathway amplifies generation of Xa Xa converts prothrombin to thrombin which then converts fibrinogen into fibrin.

External Urethral Sphincter

Ischial tuberosity to surrounding the urethra. Action: compress urethra to maintain urine continence Nerve: Pudenal (S2-S4)

Muscle mechanics and relationship between muscle force and length

Isotonic: constant tension, positive velocity and work Isometric: constant length contraction (inc in tension but no shortening), no velocity or work A muscle is composed of connective material (collagen, elastin, titin) and contractile proteins. When a muscle is at rest or even dead, if it is stretched to a longer length, the connective material will resist this increase in length just like a rubber band does when stretched. The force generated by stretching the connective material is called passive tension because it does not require the breakdown of ATP. Stretching the muscle to a given length (passive tension or preload) and stimulating it to contract isometrically, that is, activate the contractile proteins. At each stretched length, the muscle will develop an additional amount of tension called, active tension because the contractile proteins are now generating tension. Active tension is the additional tension produced by the interaction of actin and myosin. Active tension is over and above the passive tension that is developed at a particular length. Total tension is the sum of passive and active tension at any given muscle length.

Innate effector functions

Killing pathogen (phagocytosis) Communication (cytokines to attract and arm other effector cells) Presentation (display peptides for presentation to activated T cells)

Neutrophil movement during inflammation

L-selectin shredding and integrin/E-selectin binding causes adhesion leading to movement out of blood vessel (diapedesis), chemotaxis is used to find and finally phagocyte pathogen

Orbit bones, Lacrimal gland (CN7)

Lacrimal gland PNS innervation by CN VII, pterygopalatine ganglion synapse Lacrimal gland, lacrimal canaliculi, Lacrimal sac and nasoacrimal duct important for tear production and release- lack leads to infections (caused by palsy) Its course: greater petrosal n., n. of pterygoid canal, pterygopalatine ganglion, zygomatic n. (V2), lacrimal n. (V1), lacrimal gland

Larynx nerves and lymph($)

Laterally, lymphatic vessels located along the superior thyroid veins pass directly to the inferior deep cervical lymph nodes. Some lymphatic vessels may drain into the brachiocephalic lymph nodes or the thoracic duct

Nerves of Cranial Plexus 2

Lesser occipital: C2, skin of the neck and posterosuperior to the ear Great auricular: C2&3, ascends over SCM towards lower part of parotid gland. Innervates the skin over the gland, mastoid process, interior ear and angle of the mandible to mastoid process Transverse cervical: C2&3, passes over SCM going anteriorly. Supplies skin of the anterior cervical region Supraclavicular: C3&4, over SCM and down. Supplies skin over the shoulder area

Pelvic Diaphragm

Levator ani + coccygeus Supports pelvic organs, Counteracts increases in intra-abdominal pressure, Maintains urinary and faecal continence

Immunoglobulin genes/ allelic exlusion

Light chain can only be lambda or kappa (not a Hz mix though) Light chains have V, J, and C segments Heavy chains have V, J, C and D segments. Adaptive diversity via recombinations. Allelic exclusion needed for high-avidity binding and BCR cross-linking, Hz show low-avidity binding and no cross links. All the antibodies made by a B cell are identical. Allelic exclusion occurs due to gene rearrangements of demethylated alleles wtih security checks.

Ansa Cervicalis C1-3 (of Neck)

Loop of nerves from the cervical plexus which innervate the infrahyoid muscles C1 via CNXII is the superior root, C2&3 are the inferior root

Thymus has dual embryonic origin

Lymphocytes from bone marrow (mesenchyme/mesoderm) and epithelial reticular cells from endoderm

M cells of the gut

Lymphoid nodules of GALT are isolated from the lumina of their respective tracts by microfold (M) cells. They transfer antigens from the lumen (by phagocytosis and pinocytosis) and present them (without processing them to epitopes M cells are not APCs) to lymphocytes and macrophages on their basal cell surfaces: immune response is generated in the underlying lamina propria

a1-antitrypsin

M (normal) and Z (nonfunctional allele: lack of proper secretion: leads to pulmonary emphysema in teens) synthesized by hepatocytes (hepatocyte disorders possible)

Complement system: lectin pathway

MBL (liver protein via IL-6 also gives CRP: C reactive protein) a type 1 PRR, MBL acts like C1

Immune response to viruses ($)

Macrophage picks up virus and makes IL 12 which helps NK cells make IFN-y. In lymph nodes dendrites and macrophages (APCs) hook up with Cd- 4 T cells in presence of IL 12 making IFN-y which turns CD4 cells into Th1 cells. Th1 cells secrete IL 2, IFN-y and CD40L which help dendrite cells to activate CD8 (due to higher threshold) APCs also hook up with CD8 T cells which become cytotoxic which leave lymph and kill off infected cells with granzyme, perforin, or fas ligand (leads to apoptosis) Antibody production occurs too in the same way as bacteria (cell needs INF-y and IL 4 to make IgG to bind cells with virus) antibody cell cytotoxicity if killed by NK.

Bone functions

Main Functions: 1. Provide mechanical support for internal organs (ribs) 2. Permit locomotion via tendons 3. Protection of vital organs (skull) 4. Metabolic reservior of mineral salts ( 99 % of Ca) Composition : Cells & Extracellular Matrix 1. Support cells - osteoblast and osteocytes 2. Resorption and Remodeling cells - osteoclasts 3. Matrix - has inorganic mineral salts and organic materials -- non-mineralized organic matrix is called osteoid

B cell differentiation

Makes antigen reactions better (the binding that is) Plasma cells: make and secrete antibodies, IgM not surface bound anymore and is secreted, MHC class II expression stops, no longer responds to antigen Memory B cells: do not secrete Ab, survive long, activated on 2nd encounter of antigen

Urethra

Males' is longer, musculature around female bladder orifice not organized into sphincter like for males, cystisis more common in women. Male urethra has four parts, widest at ant. prostate and narrowest at intermediate (external urethral sphincter), longest corpus spongiosum.

Reticulocyte count

Marker of effective erythropoiesis: usually <3% must correct for anemia and RBC polychromasia

Hyaline Cartilage, proteoglycans, adhesive glycoproteins, ground subtance

Matrix: produced by chondrocytes has a. Coll. Type II is embedded in amorphous ground substance(GS). Can't see Coll. II because: 1. Coll. II forms bulk of fibrils 2. Refractive index - same as GS Five types are involved in the fibrils: coll. type II-- bulk ; type XI -regulates fibril size ; type IX-enhances fibril binding with proteoglycans; type X - involved in three dimensional arrangement; typeVI- attach cells to matrix Proteoglycans of GS which contain 4 types of GAGs ( chondroitin 4- sulfate, chondroitin 6- sulfate,and keratan sulfate) are linked to hyaluronic acid(GAG) to form large proteoglycan aggregates. Adhesive glycoproteins (chondronectin) which has binding sites for coll. II, GAGs, hyaluronic acid and integrins of chondrocytes. Note the hyaluronic acid aggregates are bound to the coll. fibrils by electrostatic interactions and glycoproteins Ground substance is not uniformly distributed. GS is stained with basic dyes(basophilia & metachromasia). Chondrocytes have a higher conc of sulfated proteoglycans & less coll. around the lacunae. This zone is called the territorial(tm) or capsular matrix - stained heavily. Areas between cells- stained less intensely and are called interterritorial matrix. picture: square is an isogenous group

CBC component: MCH

Mean corpuscular Hb: normal is 25-35 MCH=Hb/RBC Increases and decreases with MCV

CBC component: MCHC

Mean corpuscular [Hb]: color or chromia of RBC hypochromic: Fe deficiency hyperchromic: hereditary spherocytosis, sickle cell, homo Hb C

CBC component: MCV

Mean corpuscular volume: most important for anemia classification normal 80-100 (um^3), micro if less than 80, macro if more than 100 RBC classified as: microcytic/ normocytic, etc.

Megakaryocytopoiesis

Megakaryocyte has a lot of DNA and demarcation membranes with platelet granules, they release platelets when sheared by blood force platelets have: platelet-derived growth factor, fibroblast growth factor, von Willebrand's factor for adhesion and factor IV for blood coagulation

Wright stains

Methylene blue is a basic/positively charged dye, it stains acidic (negatively charged) cellular structures blue: DNA in the nucleus, RNA in the cytoplasm, the specific granules of basophils. These structures are said to be basophilic (base-loving). Eosin is an acidic/negatively charged dye; it stains basic (positively charged) cellular structures pink/red: hemoglobin and the specific granules of eosinophils (contains the major basic protein). These structures are said to be acidophilic or eosinophilic.

Muscular system development

Most muscles arise from the mesoderm 1) Skeletal muscle: Derived from paraxial mesoderm (myotome) Myotome of the Somites: muscles of the axial skeleton, body wall, limbs. Myotome of the Somitomeres: muscles of the head 2) Cardiac muscle: Derived from splanchnic mesoderm surrounding heart tube 3) Smooth muscle: Most from splanchnic mesoderm except the smooth muscle of the pupil (dilator pupillae, which are derived from the neuroectoderm).

Neck Lymphatics ($)

Most superficial neck tissue is drained by the superficial cervical lymph nodes located along the EJV. Lymph then drains into the inferior deep cervical nodes. The main group of deep cervical nodes form a chain along the IJV. Most of the lymph from the six-eight nodes then drains into the supraclavicular group of nodes The vessels from the deep nodes join to form the jugular nodes All lymph ultimately feed into the venous angle

Haptens

Must be with protein carrier (conjugate) to cause immunogenicity The antibody can bind to the hapten (doesn't need carrier protein present) but it will not provoke immune response (low threshold).

Chemotactically active factors

N-formylated oligopeptides of bacterial origin (mitochondria also make N-formylated proteins): ruptured mitochondria release these proteins, are chemotactic for phagocytic cells: reason for necrosis causing inflammation. Also includes chemokines (cytokine derivative).

NADPH importance

NADPH is a water soluble reductant which supplies fatty acid and sterol biosynthesis, ribonucleotide reduction and glutathione regeneration processes with reducing coenzymes Uses: 1. Reduction of NTP's to deoxy-NTP's by ribonucleotide reductase 2. Fatty acid and steroid biosynthesis in liver by fatty acid synthase and HMG-CoA reductase 3. Oxidant control in erythrocytes by glutathione reductase

Phagocyte oxidative burst (reactive oxygenation species)

NBT measures killing capacity Cells need to go from glycolysis to pentose pathway (need G6P dehydrogenase) CDD (disease) enzyme to make oxygen radicals for oxidative burst is low so killing capacity decreased

B cell activation by Antigen

Naive B cells recognize antigen and via BCR and cross links form generating signals. Signals transferred within cell by kinases leading to gene expression.

Pharynx (3 parts)

Nasopharynx: contains adenoids, may block air when inflammed. Chonae provide passageway from nasopharynx to the nasal cavity. Oropharynx Laryngopharynx

T cell central tolerance (- selection)

Negative selection (central tolerance) : when not sick own body's antigens are presented. The T cell that are self-reactive to self-peptides are taken out. Those that bind and recognize self MHC in a medium level (not too tightly) but NOT self peptides (antigen) well survive. MHCs are variable due to varying peptide anchors (similar amino acids on ends hook while amino acids in center can be whatever)

Neural crest cells and craniofacial defects

Neural crest cells contribute to the skeletal elements of the craniofacial region. Disruption results in craniofacial malformations. Since crest cells also contribute to septation of the outflow tract of the heart into pulmonary and aortic channels, many infants with craniofacial defects also suffer cardiac abnormalities, including persistent truncus arteriosus and transposition of the great vessels.

Skull embryology

Neurocranium: the protective case around the brain Vault: Membranous part (flat bones) Base: Cartilaginous neurocranium/Chondrocranium Viscerocranium: the skeleton of the face

Palates of the mouth

Neurovasculature of the Hard Palate: Emerging from the incisive foramen are nasopalatine nerves Located medial to the 3rd upper molar is the greater palatine foramen with greater palatine neurovasculature Lesser palatine foramen pierce the pyramidal process of the palatine bone Soft palate muscle: Tensor veli palatini: Tenses soft palate (CN V3) Levator veli palatini: Raises soft palate (CN X) Musculus uvulae: Elevates uvula (CN X) Palatoglossus: pulls root of tongue upward, narrowing oropharyngeal isthmus (CN X) Palatopharyngeus: Elevates wall of the pharynx (CN X) Lymph path: retropharyngeal to superior deep cervical nodes to the jugular trunks which enters the thoracic duct on the left and the right lymph duct on the right.

Differential Leukocyte Count

Neutrophils most (segmented more than banded) then lymphocytes, then (much less) monocytes, eosinophils, and basophils

Neurocranium

Newborns don't have bregma but an open space called Anterior fontanelle Viscerocranium: bones that form the face (not frontal)

Acetylcholine binding

Nicotinic Acetylcholine (ACh) receptors in the postsynaptic membrane of skeletal muscle fibers are cation channels. A) without ACh the channel is closed (prior to Ca++ release from presynaptic vesicle) B) 2 ACh molecules bind with each receptor after Ca++ release into the synaptic cleft. • Cation channel opens leading to Na+ influx and K+ outflux • Na+ influx is by far more than K+ outflux leading to a depolarization of the membrane (graded potential) ACh is released in form of one or multiple packages called a quantum (content of one vesicle = 10000 molecules). • Each quantum produces an endplate potential of 1 mV • A nerve action potential causes in average the ACh release from 100 presynaptic vesicles

Smooth muscle histology microanatomy

No sarcomeres, no myofibrils. Thick and thin filaments present; Thin filaments are composed of actin associated with tropomyosin. No troponin Thick filaments are composed of myosin with myosin heads all point in the same direction. Myofilaments criss-cross obliquely through the sarcoplasm as a latticework, attached to dense bodies. Dense bodies Present in the cytoplasm associated with the cytoplasmic side of the sarcolemma Composed of ą-actinin, thus resembling the Z lines of striated muscle Serve as insertion points for myofilaments and intermediate filaments (desmin and vimentin) to transmit force of contraction Caveolae (sarcolemmal vesicles): may associate with the sparse Sarcoplasmic reticulum; may function in release and sequestering ca++. Renewal and regeneration of smooth muscle Capable of undergoing mitosisin response to injury. Hypertrophy and hyperplasia New smooth muscle may arise from undifferentiated mesenchymalcells ( or pericytes accompanying blood vessels) .

Cancer: Activation of Ras following hormone binding EGF to a receptor tyrosine kinase ($$)

Normal: Guanine nucleotide exchange factor (GEF) activity of Sos promotes formation of the active Ras+GTP (by cleaving GDP) GTPase-activating protein (GAP) does hydrolysis of GTP regenerates inactive Ras-GDP (spont.) Ras phosphorylates MEK which does same to ERK which does same and activates transcription factors. Cancer: Ras proto-oncogene becomes an oncogene by substitution of any AA for glycine to valine at pos. 12 of the AA sequence. Reduces the Ras GTPase activity (const. active) Ras was found from bladder carcinoma

Reason for pentose phosphate flux in cells

Normal: DNA damage repair Activation of p53 by DNA damage enhances oxidative pentose phosphate flux. Cells generate NADPH and ribose 5-phosphate (R5P) for nucleotide synthesis and DNA repair. Cancer: Tumors express pyruvate kinase M2 (PKM2) and transketolase-like 1 (TKTL1). The amount of NADPH produced by the PPP decreases. Cancer uses TCA cycle more.

Cancer: c-Src and V-Src ($$)

Normal: Kinase activity of c-src inactivated by phosphorylation of the Tyrosine 527, which is six residues from the C-terminus. Hydrolysis of phos-tyrosine 527 activates c-Src. Cancer: v-src from Rous sarcoma retrovirus: deletion that eliminates the C-terminal 18 amino acids of c-Src making the v-Src kinase constitutively active due to missing tyrosine 527

Cancer: loss of TGFβ receptors

Normal: TGFβ induces expression of p15, leading to arrest in G1, and synthesis of extracellular matrix proteins such as collagens and plasminogen activator inhibitor-1. Cancer: Loss of TGFβ receptors or Smad 4, a characteristic of many human tumors, abolishes TGFβ signaling. This promotes cell proliferation and development of malignancy.

Dendritic cell

Not a neuron, the best and probably the most important APC in the whole immune system, found in thymus medulla and negatively select thymocytes to die. Called Langerhan's cells in skin.

T to R State Transition in Hb

O2 binds in active site, once it binds rapid relaxation of subunits to R state. BPG binds to regulatory site and effects all four chains, B-chains further apart in T state, F helix alteration changes tertiary shape. BPG and salt bridges intact in T state. BPG released and bridges broken in R state. BPG binds to 1 Lys and 2 His on each of two B chains (BPG is negative).

Thymic nurse cells

One thymic nurse cell can contain ~7-50 thymocytes TNCs provide a microenvironment that optimizes T-cell selection

Middle cranial fossa

Optic canal: CN II Superior orbital fissure: CN III - IV - V1 - VI Foramen rotundum: CN V2 Foramen ovale: CN V3 Spehnoid bone most anterior, temporal and parietal bones also present here.

Cancer: loss of tumor-suppressor genes p16 and RB

Over-expression of the proto-oncogene encoding cyclin D1 or loss of the tumor-suppressor genes encoding p16 and Rb can cause inappropriate, unregulated passage through the restriction point in late G1, a key element in cell-cycle control. Inheritance of a single mutant allele of many tumor-suppressor genes (e.g., RB, APC, and BRCA1) increases to almost 100 percent the probability that a specific kind of tumor will develop. Loss of heterozygosity of tumor-suppressor genes occurs by mitotic recombination or chromosome missegregation.

Erythrocyte Reactive Oxygen Control

Oxidants cause lipid oxidation and membrane disruption. Low Hematocrit indicates anemia.

Junctional diversity generation in Ab chains

P and N nucleotides added by TdT (terminal deoxy nucleotide transferase)

Hormonal Activity (related to bone)

PTH (parathyroid gland) . Low levels of PTH stimulates osteoblasts and bone formation whereas high levels stimulate osteoblasts to release osteoclast-stimulating factor (RANKL). RANKL binds to RANK on immature osteoclasts . This results in increase # and activity of osteoclasts thus causing an increase in bone resorption. Calcitonin from C-cells or parafollicular cells of thyroid acts on osteoclasts directly by reducing osteoclast activity thereby inhibiting bone resorption Somatotropin (pituitary growth hormone) from pars distalis of pituitary gland stimulates growth especially from the epiphyseal plates. It influences bone dev via the liver which produces somatomedins (insulin -like growth factor) which then stimulates growth of the epiphyseal plates. Lack of this hormone -dwarfism in children.Excess- gigantism

Two Cranial nerve rules

Parasympathetic (GVE) fibers reside ONLY in Cranial Nerves: -CN III -CN VII -CN IX -CN X These nerves have associated ganglion: -CN III = Ciliary Ganglion -CN VII = Pterygopalatine & Submandibular Ganglion -CN IX = Otic Ganglion -CN X = Ganglion near visceral organs Branchial Motor (BE/SVE) fibers reside ONLY nerves associated with pharyngeal (branchial) arches: -CN V3 (arch I) -CN VII (arch II) -CN IX (arch III) -CN X / XI (arch IV & VI)

Larynx

Part of the Respiratory System Organ of phonation Valve - regulates the air flow Connects - oropharynx with trachea Located at the level of C3-C6 vertebral bodies 9 cartilages + membranes and ligaments + vocal folds

Macrophages (for everything)

Part of the initial wave responding to an infection, kill many pathogens, recruit neutrophils, and help initiate the adaptive response, also removes dead tissue Killing: Highly phagocytic iNOS (nitric oxide) Respiratory burst

Immune response to worms ($)

Partly eaten by NT and macrophages which transfer to dendritic cells in the gut to activate Th 0 cells in presense of IL4 . Th 2 response makes IL4 stimulating B cells to presenting IgE (leads to eosinophilia) Mast cells and eosinophils have Fc epsilon receptors to capture IgE which make sensitized cells which go to gut and IgE on surface of the cells to bind the worm. Mast cells degranulate to disintegrate worm surface. With worm infections IL 4 works on mast cells to release histamine which works on gut epithelium to induce peristalsis and mucus production (expel the worm with slippery surface)

Microbial ligands recognized by PRRs

Pathogen Associated Molecular Patterns - PAMP Bacterial Associated Molecular Patterns - BAMP Damage Associated Molecular Patterns- DAMP PAMP: not shared with the host, common to many pathogens, invariant TLRs recognize certain PAMPS

Plasma cholinesterase

Plasma cholinesterase: found in plasma and synthesized in liver Catalyses hydrolytic cleavage of various esters of choline, degrades drugs such as anesthetics and cocaine. Acetylcholinesterase found predominantly in nervous tissue and erythocytes Increased levels: nephrotic syndrome, hint to hepatic disease (if in plasma) organophosphates inhibit cholinesterase: seizures treat with atropine sulfate (ACh antagonist)

Plasma versus serum

Plasma contains all the proteins, serum has lost fibrinogen (among others) in clot. Hematocrit is RBCs in plasma (42-47%). Blood is collected in the presence of a anticoagulant in plasma (like heparin). Blood naturally coagulates in serum. Blood clot strings are fibrinogen.

Epitopes

Portion of antigen that binds ONE specific antigen recognition molecule Number of epitopes = valence of the antigen linear epitopes can lead to peptides which are recognized by TCRs conformational epitopes can only be recognized by Ab

Red Blood Cells

Primary function is the transport of O2 and CO2. No nucleus or organelles, RBCs make up 99% of all blood cells. Males have more. RBCs form 35-50% of the volume of whole blood. Four main components: 1) plasma membrane, 2) cytoskeleton, 3) hemoglobin (95% of content), 4) glycolysis enzymes RBCs get energy from plasma glucose, 120 day lifespan (new ones called reticulocytes). Biconcave shape max. surface area/volume ratio. 8um is normal, 6um is microcyte, 9 um is macrocyte.

Primary v. Secondary Lymphoid Nodules

Primary lymphoid nodules contain small, immature B cells. Have both naïve B and B memory cells. NO germinal center. Secondary lymphoid nodules are the result of the arrival of APCs and recognition of the antigens. B cells are activated and they will proliferate in the central portion of the nodule, which then stains lighter and is called germinal center.

Thymus

Primary lymphoid organ (CFU cells to T cells), thymic involution with age from major immune site to fatty tissue. Contains trabeculae (canals) in parenchyma (functional part) of the organ containing blood, efferent lymph vessels, etc. Trabeculae establish thymic lobules with *dark basophilic, purple cortex* and *light, eosinophilic pink medulla* Cortex richer in lymphocytes. Capsules and trabeculae formed by fibroblasts.

Lymphoid organs

Primary/Central (maturation and developmental site): Bone Marrow and Thymus Secondary/Peripheral (where immunocomp. cells interact): MALT, SALT, GALT, BALT, tonsils, LYMPH NODE and spleen

Pentose Phosphate Pathway

Products : 2 NADPH, CO2, ribose (using ribulose). Regulation: Glucose 6-phosphate DH is inhibited by high NADPH/NADP+. Important for nucleotide synthesis.

Class II MHC process ($)

Professional APC takes pathogen from outside and engulfs it making a phagosome which will fuse with lysosome (phagolysosome) yielding peptides. MHC molecules (in ER) go through golgi pathway, secretion vesicles merge with phagolysosomes and peptides meet MHC II molecules and are presented to CD4 cells to make cytokines IL2 (prolif.) or IL 13 for extra cellular pathogens or Th 17 which secretes IL 17 for fungi, etc.

Role of Thrombin in Coagulation

Promotes platelet aggregation, Initiation of the intrinsic pathway and amplification of the coagulation cascade, Activates factors V and VIII responsible for formation of tenase and prothrombinase complexes, formation of the insoluble fibrin meshwork, can inhibit fibrinolysis by fibrinolysis inhibitor (needs thrombin)

Role of Protein C in Regulation of Coagulation

Protein C (PC): Trypsin like serine protease; serves as a major regulator of coagulation Protein S (PS): Serves as a cofactor of activated protein C (aPC) Protein S and C Vitamin K regulated Thrombin bound to the endothelial proteoglycan thrombomodulin cleaves the activation peptide of PC thus activating it to aPC (Va and VIIIa which prothrombinase and tenase complex formation) end result: no factor X activation or thrombin addition PAR-1 (aPC binds to EPCR): cyto-protective and anti-inflammatory response in endothelial cell

Testing coagulation cascade efficiency

Prothrombin Time (PT): efficiency of the extrinsic pathway (test clotting factors and fibrinogen) Normal value: 11-15 sec Partial Thromboplastin Time (PTT or aPTT): efficiency of intrinsic and common pathways Normal value: 25-37 sec Bleeding Time: Normal value: 2-5 min

Levator ani (3 parts)

Pubococcygenus (PC ) stretches from the pubic bone to the coccyx (tail bone) Controls urine flow and position the baby's head during childbirth. Iliococcygenus (IC) arises from the ischial spine, super ramus of the pubis, and attached to the coccyx. Helps for vaginal contraction. Puborectalis (PR) (sphincter ani externus) from lower part of the symphysis pubis, and superior fascia of the urogenital diaphragm, meets corresponding fibers of opposite side around the lower rectum. Relaxation reduces the angle between rectum and anus, allowing defecation in conjunction with relaxation of the internal and external sphincters.

Overview of Lymphatics: Drainage of the Lungs

Pulmonary plexus has deep and superficial plexuses. Superficial plexus drains the visceral pleura and parenchyma into the bronchopulmonary lymph nodes (hilar lymph nodes) Deep plexus drains structures from the root of the lung into pulmonary lymph nodes on the lobar bronchi They will then drain into the bronchopulmonary lymph nodes also. Both plexuses will then drain into the superior and inferior tracheobronchial lymph nodes (at the bifurcation of the trachea) Superior and inferior tracheobronchial lymph nodes drain into the bronchomediastinal trunks and then into the thoracic duct on the left and the right lymphatic duct on the right

Temperature Regulator receptors and Fever ($)

Receptors: Z1 feels warmth and makes you cooler Z2 feels cold and makes you warmer Fever: first part of fever in warming the core: shivering, and skin perfusion decreases, perceived as cold recovery is cooling the core so you sweat and feel warm, skin perfusion inc.

Two types of bone marrow

Red bone marrow - color is produced by the presence of blood and blood-forming cells, Yellow bone marrow - color is produced by the presence of a great number of adipose cells. Newborns have all red bone marrow but adults only have high amounts in (cancellous bone) hips, ribs and skull, but blood marrow type can convert in severe blood loss

Cardinal Inflammatory response signs

Redness - rubor Warmth - calor Swelling - tumor Painful - dolor Loss of function

Proximodistal development of the limbs

Regulated by AER (Apical ecteodermal ridge: Ectodermal thickening at the distal border of the limb). Mesenchyme close to AER remains undifferentiated and keep proliferating (progress zone), and mesenchyme farther from AER become differentiation into cartilage and muscle

Patterning of the anteroposterior axis of the limb

Regulated by ZPA (Zone of polarizing activity: a cluster of cells at the posterior border of the limb near the flank) Rotation of the limbs In week 7,upper and lower limbs rotate in opposite directions. Upper limbs rotate 90 degrees laterally and the lower limbs rotate 90 degrees medially.

Overview of Lymphatics

Regulates the amount of interstitial fluid (reverse osmosis/edema without the system). Lymphatic plexuses are with capillary beds and have blunt ends and no basement membrane. Lymphatic vessels are one way and valved. Lymph nodes have afferent and efferent vessels. Two "sections" Cortex: the outer part containing follicles - collections of lymphocytes and the inner Medulla: contains phagocytic macrophages. Lymphatic vessels: Superficial vessels are located in subcutaneous tissue and follow the venous return, eventually draining into the deep lymphatic vessels. Deep vessels accompany the arteries, which help "milk" them. Lymph eventually joins venous angles through r. lymphatic duct or cisterna chyli (L1/L2 level). Thoracic duct at level T5. Thymus Gland: Produces hormone thymosin which helps in programming T-lymphocytes. T cell maturation happens here.

Myosin activation and the Power Stroke in smooth muscle

Regulation occurs by altering the properties of myosin (instead of thin filament like in skeletal) which is called thick filament regulation. The myosin alteration is phosphorylation of myosin. Myosin phosphorylation is controlled through an enzyme cascade involving a calcium binding calmodulin (CaM), and enzyme myosin light chain kinase (MLCK). Calcium in the cytoplasm binds to calmodulin. The Ca-calmodulin complex binds to MLCK and activates the enzyme. Active MLCK phosphorylates the light chain in the head region of the myosin molecule causing a conformational change that enables myosin to bind to actin. Once myosin light chain is phosphorylated, cross-bridge cycling occurs in the the same way as in skeletal muscle until the light chain is dephosphorylated by myosin light chain phosphatase (MLCP) after its detachment from actin.

Intercalated discs (cardiac muscle)

Represent specialized cell junctions between cardiac muscle cells. Interdigitating folds of sarcolemma at the end of adjacent cells, linking them structurally and functionally

Heme Biosynthesis

Required for efficient erythropoiesis - glycine, B6 and iron requirements. Impaired biosynthesis results in disorders called Porphyrias. These disorders result in cutaneous and/or neurologic manifestations. Lead inhibits final step of adding Iron cofactor.

T cell activation ($)

Requires three signals: Signal #1: TCR: peptide + MHC Signal #2: CD28 and B7 (CD86) (Co-stimulation without it T cell is anergic) Signal #3: cytokines (like IL-2 which is self secreted for proliferation, other also for differentiation) <----exam question!

Boundaries of the Nasal Cavity

Roof: frontal, ethmoidal and sphenoidal parts Floor: palatine process of the maxilla, horizontal plate of the palatine bone Medial wall: nasal septum (attaches to cribiform plate, inn. by nasopalatine n.) Lateral wall: 3 nasal conchae

Tympanic Membrane and Pharyngotympanic Tube

Separates the external acoustic meatus from the middle ear Receives sound waves and transmits oscillations to the ossicles Innervated by the auriculotemporal nerve of V3 which appears to only perceive pain Minor contributions from CN VII & CN X (cough efferent or vagal stimulation as when syringing the ear) on the outer part of the membrane and CN IX (gag afferent) on the inner part of the membrane Pharyngotympanic Tube: Supplied by the ascending pharyngeal artery, middle meningeal artery and artery to the pterygoid canal Lymphatic drainage to the deep cervical nodes Innervated by tympanic plexus (CN IX) as well as the pterygopalatine ganglion

Scalp layers

Skin Connective tissue (dense) Aponeurosis Loose connective tissue Pericranium (initial spread of infection of scalp is through areolar tissue)

Lymphatic sinuses

Small afferent lymphatic vessels penetrate the capsule of lymph node and open into an endothelial-lined (1) subcapsular sinuses and (2) peritrabecular sinus, which lead to a meshwork of (3) medullary sinuses in the medulla. Medullary sinuses become larger channels that combine to form the (4) efferent lymphatic vessels that exit at the hilum.

Organization of smooth muscle cells

Smooth muscles are stimulated to contract through nerve stimulation or circulating chemical agents. In some smooth muscle containing organs smooth muscle cells are electrically coupled through gap junctions. Because of these electrical connections stimulation of one smooth muscle cell will lead to stimulation of all cells that are coupled, contracting as a single unit. Therefore called single unit smooth muscle. In other smooth muscle containing organs (e.g. blood vessels) the cells are not electrically coupled through gap junctions. Each smooth muscle cell has to be individually stimulated by a nerve or chemical agents. They behave as multiple units and are called multiunit smooth muscle.

Skeletal muscle

Somatic motor neuron innervation Motor unit: The lower motor neuron and the muscle fibers it innervates A single motor neuron action potential results in an endplate potential and an action potential in the skeletal muscle. Structure: synctium: many nuclei within a cell/fiber. Each skeletal muscle cell forms from fusion of many precursors (myoblasts) Each cell is cynlindrical Cytoplasm contains contractile proteins, abundant mitochondria and glycogen, myoglobin External lamina surrounds each cell. Some precursor cells remain in adults called satellite cells (can form new muscle with tissue damage)

Thymus-independent (TI) antigens ($)

Some bacterial antigens can stimulate naïve B cells in absence of T cell help. Ex: Polysaccharides, Polymeric Proteins (repeating polymers like dextran), Lipopolysaccharides Signal #2 comes from antigen itself Signal #2 is necessary for B cell activation by T-dependent and T-independent antigens

Smooth muscle histology overview

Specialized for prolonged, slow contraction No cross striations, no T tubules Found as sheets forming the walls of hollow organs (except the heart), blood vessels and secretory ducts, small bundles in dermis; innervated by ANS Function: movements of hollow organs (peristalsis) Smallest fiber type (20um long in BV, 500um in uterus) Elongated cells, spindle-shaped, non-branching Single, centrally located nucleus; appear "cork-screw" in contracted state. External basal lamina present, reticular fibers surround bundle

Meatuses

Spheno-ethmoidal recess: drains sphenoidal sinus Superior meatus: drains the posterior ethmoidal sinus Middle meatus: 2 parts (contains ostium of maxillary sinus) Hiatus semilunaris for the frontal, anterior enthmoidal and maxillary sinuses Ethmoid bulla for the middle ethmoidal sinus Inferior meatus: drains the nasolacrimal duct

Splenic venous sinuses and stave cells

Splenic venous sinuses (S) are lined by endothelial cells (arrows) that are called stave cells These are elongated endothelial cells that are oriented in parallel with the sinusoid's blood flow. Stave cells are sparsely wrapped in reticular fibers and remove old RBCs (120 days+ which swell and aren't as flexible) The killed RBCs release Fe shuttled by transferrin to bone marrow, the heme either becomes bilirubin or is transported by hemopexin

Fixed cells

Stable and long lived, include: Fibroblasts, Adipose cells, Pericytes (around blood vessels), Mast cells and Macrophages

T cell development and + selection ($)

Stem cells go to thymus from bone marrow, try to rearrange chains to make functional beta chain. They need surrogate chain (pre-T alpha chain) making pre T cell receptor (only has functional beta chain). Cells are called double negative (non CD4 non CD8). Once they have receptor they proliferate. Both CDs get expressed (double positive), get functional alpha chain. In the thymus there is positive selection. Professional APCs (thymic epithelial cell etc.) in stroma hook T cell with MHCI or MHCII. If the binding is more efficient with MHCII then CD4 is selected, then CD8 gets repressed. If MHCI interaction is greater than CD8 is favored.

Cancer: Misexpressed Growth-Factor Genes

Stimulate cell proliferation. Sis is the only naturally occurring GF oncogene found. It encodes PGEF which overstimulates platelets. Ex) HPV: an E5 polypeptide can form a stable complex with one endogenous receptor for PDGF (simulates dimerization = activation) Erythroleukemia and Polycythemia vera

Sarcoplasmic reticulum

Stores calcium for muscle to use once action potential is felt. Contains a Triad with terminal cisternae at A-I junction and T- tubules between them.

Red Bone Marrow

Stroma: 3-dimensional meshwork of reticular cells and a delicate web of reticular fibers containing hematopoietic cells, macrophages, and a few adipocytes, has hemonectin to bind cells to reticular fibers Sinusoids: formed by sinusoidal capillaries: where formed elements enter bloodstream

Arteries of the Root of the Neck ($)

Subclavian artery: Vit C D Divided into three parts by scalene anterior Vertebral Internal thoracic Thyrocervical: inferior thyroid, suprascapular and transverse cervical Costocervial: superior intercostal and deep cervical Dorsal scapular

Supraclavicular Triangle

Subclavian vein and artery Brachial plexus Phrenic nerve Suprascapular and transverse cervical arteries

Submandibular Glands

Submandibular: Presynaptic PNS from CN VII, via Chorda Tympani, synapse within the submandibular ganglion. Post-synaptic axons follow the artery with the vasoconstrictive post-synaptic sympathetic fibers from the superior cervical ganglion. Sublingual glands good for taking drugs

Pelvis minor

Superior aperture: 60-65º, Terminal line (linea terminalis): Inferior aperture: 10-15º, Coccyx and Sacrotuberous lig.

Sympathetic Ganglia

Superior cervical ganglion: adjacent to C1 & C2; postganglionic axons project to target: (heart, head, neck) via "hitchhiking" on the carotid arteries Middle cervical ganglion: adjacent to C6; postganglionic target: heart (cardiopulmonary splanchnic), neck (periarterial plexus) Inferior cervical ganglion: The inferior ganglion may be fused with the first thoracic ganglion to form a single structure, the stellate ganglion. Adjacent to C7; postganglionic target: heart, lower neck, arm, posterior cranial arteries

Pharyngeal Musculature

Superior pharyngeal constrictor, Middle pharyngeal constrictor, and Inferior pharyngeal constrictor constrict the wall of the pharynx during swallowing internal longitudinal muscles are: Salpingopharyngeus, Stylopharyngeus, Palatopharyngeus These muscles elevate the larynx and shorten the pharynx during swallowing and speaking Thin external fascia called the buccopharyngeal fascia, which blends with the pretreacheal layer of the deep cervical fascia contracts involuntary so that the contractions occur from superior to inferior, thereby pushing the food down the esophagus

The B cell receptor

Surface bound Complexes with IgA and IgB which mediate intracellular signaling CD19 (signalling chain) , CD21 (AKA Complement Receptor 2, recognizes C3d fragments on pathogens), CD81 activation of B cell leads to - Somatic hypermutation, affinity Maturation, and class switch

T cell receptor and co receptor (diff. from B cell receptor)

T cell receptor is either aB which needs MHCs and peptides or yD (gamma-delta) which doesn't need MHCs and can use antigens. T cell Co-receptors: CD4 with MHCII and CD8 with MHCI. MHCII are professional antigen presenting cells (macrophages, dendritic cells, B cells) Also has CD3 for signalling (always needed). B cell receptor: has IgB and Ig-a co receptors B cell receptor can cross link an antigen but not T cell receptor.

Mechanisms to maintain body temperature

TA (°C): TCore is regulated by: 5 - 25 Heat production (shivering) 25 - 35 Heat loss (skin perfusion) 35- 40 Heat loss (skin secretion) Reduced sweat sensitivity (via hypothalamus): low skin temp and dehydration Increased sweat sensitivity: High skin temperature and physical training

Muscles of Mastication

Temporalis- elevation, retrusion (posterior fibers) and lateral movement Masseter- elevation, protrusion, and lateral movement Both are innervated by the V3 mandibular nerve deep: Lateral pterygoid- depression, protrusion and contralateral movement Medial pterygoid- elevation, protrusion, and contralateral movement Both are innervated by the V3 mandibular nerve

Spleen anatomy 2

The Splenic artery divides inside the hilum, branching into trabecular arteries which leave the trabeculae and enter the parenchyma as arterioles enveloped by T lymphoctes, the periarteriolar lymphoid sheath (PALS), which is part of white pulp. Surrounded by the PALS, these vessels are central arterioles. The white pulp functions as a lymph nodule producing B cell clones in the presence of T cells derived from the PALS. Emerging from the white pulp, the central arteriole branches as the penicillar arterioles, which lead to sheathed capillaries. From these, blood flows into an open circulation, being dumped from the vasculature into the lymphoid tissue of the red pulp's splenic cords. Di George syndrome: reduced T cells in PALS

Smooth muscle length/force relationship

The active tension curve is much broader than that for skeletal muscle, due to the fact that thick filaments are longer than in skeletal muscle and so force can be developed over a greater range of stretched lengths. Also, myosin molecules organize into thick filaments differently in smooth muscle, allowing thin filaments to remain in contact with thick filaments over greater stretched lengths. Second, passive tension is greater at the optimal length than in skeletal muscle. Smooth muscle cells form the walls of hollow structures are imbedded in connective tissue. The greater amount of connective material results in a greater passive tension. The maximum force generating ability of smooth muscle at its optimal length is comparable to that seen in skeletal muscle.

Innervation of the Parotid Sheath ($)

The auriculotemporal (V3) nerve and great auricular nerve (cervical plexus C2&3) innervate the parotid sheath and the overlying skin Innervation chain of parotid gland (high yield): glossopharyngeal n. then tympanic nerve then tympanic plexus, lesser petrosal, otic ganglion, auriculotemporal

Significance of the HK-2/VDAC/ATP synthasome complex

The binding of HK-2 to VDAC prevents Apoptosis Inducing Factor (AIF) from being released from the mitochondria thereby preventing apoptosis. If AIF is expressed caspases destroy everything. Why have HK2-VDAC on outer mitochondrial membrane? HK2 has available ATP for phosphorylating glucose and keeping it to make lactate and NADPH.

Mechanism of penile erection

The cavernous nerves (autonomic), which travel posterolaterally to the prostate, enter the CC and CS to regulate penile blood flow. The dorsal nerves (somatic), which are branches of pudendal nerves, are primarily responsible for penile sensation. During erection: relaxation of the trabecular smooth muscle and vasodilatation of the arterioles Flaccid: sympathetic active, erect: parasympathetic active neuromediators:for erection: dopamine and NO (inc. cGMP for smooth muscle relaxation). for ejaculation: dopamine and seratonin

Structural basis of contraction

The contractile element of skeletal muscle cells are myofibrils Myofibrils are composed of overlapping, repeating assemblies of thick (myosin) and thin (actin) filaments. Within each skeletal fiber, hundreds of myofibrils run parallel along its length, and the alternating zones of thick and thin filaments create striations. With accessory proteins, myosin and actin form the functional unit (sarcomere) in each myofibril. Alignment of myofibrils gives a banding pattern (cross striation). Light (I) band and dark (A) bands are easily seen under LM, sometimes the thin Z line is visible in the center of the I bands. Desmin hold myofibrils together. During contraction, sarcomeres shorten with Z lines drawn together. A bands remain the same, I and H bands diminish in width.

Female external vestibular glands

The greater vestibular glands (Bartholin glands): located in the superficial perineal pouch on either side of the vestibule, secrete mucus into the vestibule during sexual arousal (site or origin of most vulvar adenocarcinomas) The lesser vestibular glands (Skene's paraurethral glands):located on either side of the vestibule of vagina, open into vestibule it between the urethra and introitus, secrete mucus: moistens the labia and vestibule.

Innervation of the Nasal Cavity

The olfactory nerve (CN I): nerve associated with the sense of smell Arises from the cells in the olfactory epithelium in the superior lateral and septal parts of the nasal cavity Posteroinferior portion: Maxillary nerve (V2)- nasoplatine n. to the nasal septum and greater palatine nerve to the the lateral wall Anterosuperior portion: Ophthalmic n. (V1)- anterior and posterior ethmoidal branches of the nasociliary nerve

Hematocrit

The percentage by volume of packed red blood cells in a given sample of blood after centrifugation. 40-50% in males, 35-45% in females.

Perineal membrane and body

The perineal membrane stretches between the two sides of the pubic arch and covers the anterior part of the outlet. The perineal body is an irregular fibromuscular mass located between the anal canal and the perineal membrane

Smooth muscle active force development and velocity

The relationship between active force development and shortening velocity differs from skeletal muscle in that in smooth muscle, velocity is lower at any level of active force. Notice that the maximum velocity is lower too, which reflects the slower myosin ATPase activity of smooth muscle myosin. Smooth muscle has high force generating ability and slow velocity of shortening, making it mech. efficient. Cycling of the cross-bridge (myosin ATPase activity, shortening velocity) consumes ATP. Smooth muscle myosin cross-bridges remain attached to actin (maintains force) longer during each cycle and so can develop force with less ATP consumption. This is very important to smooth muscle function, which is primarily maintaining long sustained contractions.

CN X

The vagus nerve provides four major branches in the neck: Pharyngeal branches (principal motor nerve to the pharynx, contributes to the pharyngeal plexus supplying muscles and mucus membranes of the pharynx) Superior laryngeal branches 3R. Right recurrent laryngeal n. 3L. Left recurrent laryngeal n. Cervical cardiac branches (convey presynaptic parasympathetic and visceral afferent fibers to cardiac plexus of nerves) not the same as but communicate with the cardiac nerves in the cardiac plexus

Cardiac Nerves

They include the Superior, Middle and Inferior Cardiac nerves The superior cardiac nerve arises by two or more branches from the superior cervical ganglion The middle cardiac nerve (great cardiac nerve), the largest of the three cardiac nerves and arises from the middle cervical ganglion The inferior cardiac nerve arises from either the inferior cervical or the first thoracic ganglion (stellate)

Thick v. Thin skin

Thick skin: lines palms and soles, lacks hair follicles and sebaceous glands Thin skin: has follicles/ oil glands, no stratum lucidum. individual cells of stratum granulosum (black arrow) and stratum lucidum are scattered

Thin and Thick filament physiology

Thin filament: double stranded actin with binding proteins tropomyosin and troponin. Tropomyosin regulates the binding of myosin head groups to actin. Troponin consists of 1) troponin T, which binds to a single molecule of tropomyosin; 2) troponin C, which binds Ca++; and 3) troponin I, which binds to actin and inhibits contraction. Thick filament: composed of multiple myosin II molecules. Each myosin II is a hexamer composed of two heavy chains, two alkali light chains, and two regulatory light chains. The heavy chains have three regions: a rod, a hinge, and a head region. Two globular heads at the hinge poses a site for binding actin as well as a site for binding and hydrolyzing ATP.Each head of myosin forms a complex with two light chains, one regulatory and one alkali chain. Alkali light chain stabilizes the myosin head and the regulatory chain regulates the ATPase activity of myosin. The activity of regulatory light chain is in turn regulated through phosphorylation by Ca++ dependent/independent kinases.

Lymph of scalp and face

Thrombophlebitis concern since lymph from tongue can go to IVC, carotids, rest of body

Eye movements

Thrombosis of cavernous sinus would affect lateral rectus muscles R=rectus, O=oblique

Binding proteins

Thyroxin binding globulin keeps hormones inactivated so body is not harmed

Auricle/ Pinna of Ear

Tragus (G. tragos, goat) projection overlapping the opening to the external acoustic meatus Arterial supply comes from the posterior auricular and superficial temporal arteries Sensory Innervation: Great auricular nerve (C2,3) supplies back of the ear (cranial or medial part)and the posterior half of the the lateral surface: helix, antihelix and lobule Auriculotemporal nerve (CN V3): Skin of the auricle anterior to the external acoustic meatus Lymphatics: Lateral surface of superior half drains into the superficial parotid nodes Cranial surface of superior half drains into the mastoid nodes and deep cervical nodes Remainder and lobule drains into the superficial cervical nodes

Lineages of Connective Tissue Cells

Transient cells form from hematopoietic stem cells and fixed cells from mesenchyme (Mast cell exception)

CN VII Facial Nerve Pathway

Travel through the internal acoustic (auditory) meatus and through the petrous portion of the temporal bone. BE/SVE axons exit the cranial base via the stylomastoid foramen. BE/SVE = facial expression! GVE axons travel on the chorda tympani nerve arising superior to the stylomastoid foramen. Chorda tympani nerve runs through the tympanic cavity and passes through the temporal bone at the petrotympanic fissure where it then joins the lingual nerve of CN V3 in the infratemporal fossa; then preganglionic axons synapse in the submandibular ganglion then travel to the submandibular and sublingual glands via arteries. GVE = glands! SVA axons, carrying taste perception from the anterior 2/3rds of the tongue, travel towards the brainstem on the lingual nerve of CN V3 and then transfer to the chorda tympani nerve of CN VII. SVE=taste! Greater petrosal nerve exits the petrous portion of the temporal bone through the hiatus for the greater petrosal. It joins the deep petrosal nerve (sympathetic GVE axons) to form the nerve of the pterygoid canal. That passes through the pterygoid canal and enters the pterygopalatine fossa. In the pterygopalatine fossa, preganglionic parasympathetic axons synapse in the PPG. Postganglionic fibers travel via the zygomatic branch of CN V2, and then travel to the lacrimal nerve (branch of CN V1) to reach the lacrimal gland.

Trigeminal CN V1 (Ophthalmic) Pathway

Travels under dura to the superior orbital fissure where it then branches into the frontal nerve, lacrimal nerve and nasociliary nerve Supraorbital nerve exits the cranium via the supraorbital foramen. *Posterior and anterior ethmoidal nerves exit via the ethmoidal foramina

Trigeminal CN V3 (Mandibular) Pathway

Travels under the dura to the foramen ovale. Branches leave through the mandibular foramen and mental foramen. *Mandibular division provides BE/SVE axons to the muscles of mastication.

Trigeminal CN V2 (Maxillary) Pathway

Travels under the dura to the foramen rotundum. Infraorbital nerve continues through the inferior orbital fissure, gives off the alveolar nerves and then leaves via the infraorbital foramen where it ends as superior labial nerve, palpebral nerve and nasal nerve. The zygomatic nerve passes through the inferior orbital fissure and carries GSA axons of CN V and GVE axons (parasympathetic and sympathetic) from CN VII. The zygomatic nerve branches into the zygomaticotemporal nerve and zygomaticofacial nerve It also connects with the lacrimal nerve of CN V1 to reach the lacrimal gland.

Initiation of cross-bridge cycling

Troponin complex has two pairs of Ca++ binding sites. Two high affinity sites are always occupied with Ca++. Calcium released from the sarcoplasmic reticulum binds to the two low affinity Ca++ binding sites inducing a conformational change in the troponin complex. The first effect is that the inhibitory troponin I detaches from its binding to F-actin, thereby permitting tropomyosin molecule to move. The second effect transmitted through troponin T, is to push tropomyosin away from the myosin binding site on the actin. This movement of tropomyosin uncovers binding sites for myosin on actin and induces cross-bridge cycling.

Warburg effect ($)

Tumors have enhanced glycolysis and suppressed oxidative phosphorylation. Hexokinase II and pyruvate kinase M2 are up-regulated (int products built up) Pyruvate dehydrogenase kinase up-regulated (pyruvate kept out of mito) More free radicals (ROSs) are generated and enzymes that handle ROSs are up-regulated Tumor cells obtain biosynthetic precursors from glucose and glutamine metabolism.

Middle Ear aka tympanic cavity

Two parts: Tympanic Cavity Proper- the space directly internal to the tympanic membrane Epitympanic recess- space superior to the membrane The tympanic cavity is connected anteromedially to the nasopharynx via the pharyngotympanic tube Contents: ossicles, stapedius and tensor tympani, chorda tympani, tympanic plexus Note: The mucous membranes of the middle ear and of the pharyngotympanic tube are innervated by CN IX via the tympanic plexus. Blood supply and Lymphatics: Deep auricular: branch of the maxillary artery supplying the external part of the tympanic membrane Anterior tympanic: branch of the maxillary artery supplying the internal part of the tympanic membrane Stylomastoid: branch of the posterior auricular or occipital artery supplying the posterior part of the cavity and mastoid cells Lymph drains into the parotid and deep cervical lymph nodes

Types of PRRs (pattern recognition receptors in innate immunity) ($)

Type 1: Secreted circulate in blood/lymph, mannan binding lectin, a-collectin binds to bacteria CHO to start complement system. produced by liver and induced by IL-6 Type 2: Phagocytosis affinity for mannose residues, bacteria binding, T cell antigen presenting Type 3: Signaling TLRs (toll like receptors, on macrophages and binding to pathogens leads to cytokine activity etc. can be in cell as well) and NLRs (nod like receptors, cytoplasmic) TLR4- lipopolysaccaride, TLR5- flagella, TLR 2-peptidoglycan wall in gram + bacteria, TLR3-viruses

Variants and alleles of Hb

Variants are Hb with changed amino acid content (each with different allele at DNA level) More allele combinations than variant (pretty much phenotypical representation). Alleles include those causing variant and those causing reduced function. Hz frequency high in those populations

Extrinsic Pathway (Tissue Factor Pathway)

Vascular injury releases tissue factor (factor III/ thromboplastin) Tissue factor in presence of Ca+2 activates VII to VIIa VIIa converts inactive factor X into its active form Xa Xa can generate small amounts of thrombin from prothrombin directly (required for activation of factor V to Va) It forms small fibrin clot a quick patch process

Vertebrae and Vertebral column development ($)

Vertebrae form from the sclerotome portions of the somites (paraxial mesoderm) Resegmentation of the sclerotome: the caudal half of each sclerotome grows into and fuses with the cephalic half of each subjacent sclerotome. Therefore, each vertebra is formed from the combination of the caudal half of one somite and the cranial half of its neighbour Mesenchyme contributes to the intervertebral disc; Notochord contributes to the nucleus pulposus; Myotome bridges the intervertebral discs, so muscles have the capacity to move the spine

Cardiac muscle

Very similar to skeletal muscle, Derived from splanchnic mesoderm Each cell possesses 1 or 2 large, oval, centrally located nuclei. Contain intercalated disks: specialized junctions (sarcolemma folds) between cardiac muscle cells.

Vesicle fusion with presynaptic membrane

Vesicle proteins Synaptobrevin and the two plasma membrane proteins Syntaxin and SNAP-25 bind to each other (building a core complex). This process brings the vesicle in close proximity to the presynaptic membrane, but both membranes are not yet fused together, because the fusion of both membranes is prevented by another vesicle protein synaptotagmin that binds with the core complex. • Ca++ entry and its binding with synaptotagmin (has 2 binding sites for Ca++) removes the brake function of synaptotagmin and initiates the fusion of vesicle membrane with the plasma membrane. • Energy for this process is delivered by hydrolysis of ATP by a ATPase called NSF.

ADCC: Antibody dependent cellular cytotoxicity

Virus antigen on infected cell, IgG binds to antigen FcyRIII (CD16) binds antibody NK activation (K function) K expression of FasL, Caspase activated Fas+ target destroyed

Role of Vitamins in Bone Formation

Vit D - necessary for absorption of Ca from small intestines. Deficiency of vitamin D results in poorly calcified bone. A condition called Rickets in children. In adults, this results in osteomalacia. 2) Vit C -necessary for collagen formation. Lack of this results in scurvy. 3) Vit A - lack of this inhibits proper bone formation and growth. Excess causes early ossification of epiphyseal plates

Deglutition

Voluntary: bolus is compressed against palate and pushed into the oropharynx by the tongue and soft palate Involuntary and rapid: soft palate is elevated, to close off the nasopharynx. Suprahyoid and longitudinal muscles widen and shorten the pharynx to accommodate the bolus Involuntary: sequential contractions of the constrictors squeeze the bolus into the esophagus.

Overview of Lymphatics: Embryology

WEEKS 6-9, 6 primary lymph sacs, derived from mesoderm Two jugular lymph sacs near subclavian veins with the anterior cardinals (future internal jugular vein) Two iliac lymph sacs near the iliac veins with the posterior cardinal veins One retroperitoneal lymph sac in the root of the mesentery on the posterior abdominal wall One cisterna chyli dorsal to the retroperitoneal lymph sac, at the level of the adrenal glands Lymph vessels grow from the lymph sacs. Cisterna chyli is connected to the jugular lymph sacs by 2 large channels, the right and left thoracic ducts. Anastomosis forms between the ducts, the definitive thoracic duct is formed by the caudal portion of the right thoracic duct and the cranial portion of the left thoracic duct.

Latch state (smooth muscle contraction)

When myosin is dephosphorylated while attached to actin, the crossbridge cycling slows because actin and myosin remain attached for longer durations than normal. This allows the muscle to maintain tonic contractions for long periods of time with reduced energy requirement for ATP and at a reduced intracellular calcium concentration.

High endothelial venules (HEV) only in lymph nodes!

Where most lymphocytes enter lymph nodes and some other lymphoid tissues from bloodstream (they come in as naive and after become effector cells) In contrast, the antigens and APCs enter through lymph Most lymphocytes enter through HEVs Located in paracortex of lymph node, as well as tonsils, Peyer patches, appendix, and aggregates of lymphoid tissue GI. (not found in spleen, where blood exits through open arterioles and enters the red pulp) Movement of T and B lymphocytes across HEVs into lymph nodes is called homing. After entry into lymph node, T cells remain in the thymus-dependent deep cortex while the B cells migrate to the nodular cortex

Common steps of Extrinsic and Intrinsic Pathways

Xa generated by both the pathways Prothrombinase complex (Xa and membrane bound Va-due to Ca++) Xa catalyzes release of a γ-carboxyglutamate fragment: prothrombin (factor II) into thrombin (factor IIa) Thrombin catalyzes conversion of fibrinogen into fibrin monomers (soluble) which polymerizes into insoluble fibrin polymers catalyzed by factor XIIIa

Boundaries of the Parotid Region

Zygomatic arch External ear and anterior Sternocleidomastoid muscle Ramus of the mandible Angle and inferior border of the mandible Anterior border of the masseter Contents of the Parotid Region Parotid gland Parotid duct Parotid plexus of facial nerves (CN VII) Retormandibular vein External Carotid artery Masseter muscle

Structure of T Cell Receptor

a chain is like light chain in Ab beta chain is like heavy chain in Ab

Rhythmic changes in Tb

a. Circadian rhythm b. Long period variability (Ovarian cycle) temperature increase post ovulation

Diameters of the lesser pelvis

a: superior aperture b: cavity (amplitudo pelvis) (greatest diameter) c: angustia pelvis (smallest diameter) d: inferior aperture House glass form

Alkaline (ALP) and Acid (AP) phosphatase

active in bone and liver, ALP: bile and bone diseases, more active in children AP: prostate problems, we use PSA tumor marker now

Platelets (pre-clotting)

aka thrombocytes are not cells but derivatives of megakaryocyte. Primary function of preventing excessive bleeding after injury. Process of vessel wall adhering is hemostasis (blood kept within damaged blood vessel). They have extensive cytoskeletons (actin-myson essential for clots). Factors for clotting include: von Willebrand factor (platelet adhesion), platelet factor IV (stimulates blood coagulation)

Chromosomal Arrangement of the Heavy and Light Chain Genes

all have a promoter and leader in front RSS: recombination signal sequence (V with J) lambda light chain has 30V and 4 J-C regions kappa light chain has 40V and 5 J and a Constant region Heavy chain has 40-65V, 25-27 D, 6 J and 8 C Heavy chain constant region goes u (M) then delta (D) For combinatorial diversity (Ab binding sites): multiple V and J (and D if heavy) together. (doesn't take random TdT addition into account)

Hemoglobin Gene expression

alpha almost always present, beta present a few months after birth onwards, fetal gamma takes beta role till then

Penile arteries and veins

arteries: from internal pudendal (which is from external iliac aa) with three branches: dorsal, cavernous branch aka deep artery (inside the corpora cavernosa), and bulbourethral arteries (run inside of the corpora spongiosa, gives off branches which ramify in the bulb of the urethra) veins: superficial and deep dorsal

Types of cytokine activity, JAK STAT ($)

autocrine (same cell), paracrine (nearby cell), endocrine (distant cell)

Albumin removal

by pinocytosis or Asialoglycoprotein receptors in hepatocytes (removal of sialic acid first by neuraminidase)

Eosinophils

bilobed nucleus, function in parasitic infections, allergy and asthma control, and phagocytosing antigen-antibody complexes, contain pink eosinophilic specific granules and lysosomes. granule includes dark highly basic internum portion (harm PM proteins) and lighter externum. Release of basic proteins also harms own cells.

Ischioanal fossa

boundaries:Anterior: the sphincter urethrae, deep transverse perineal muscles Posterior: the gluteus maximus, sacrotuberous ligament Superomedial: External anal sphincter, levator ani muscles Lateral: obturator fascia covering obturator internus Floor: the skin over the anal triangle Contents: Ischioanal fat: allows distention of the anal canal/accommodate the fetus during childbirth, inferior rectal nerves and vessels,perineal branches of the posterior femoral cutaneous nerve, Pudendal (Alcock's) canal : fascial canal (split in the obturator internus fascia and transmits pudendal nerve and internal pudendal vessels.)

Greater and Lesser Pelvis

boundary is pelvic brim

Maxillary artery

branches: Middle meningeal Inferior alveolar Muscular branches Anterior deep temporal Posterior deep temporal Buccal Sphenopalatine

Lymph

clear fluid that circulates around body tissues. Plasma leaks out of the capillaries to surround the tissues. Then drains into the lymphatic vessels. Unlike the circulatory system, all lymph flows in one direction-towards the heart, and is filtered through lymph nodes on the way ~3 liters per day move through lymphatic system Lymph dumps back into veins at thoracic duct and right lymphatic duct

Failure of palate fusing

cleft lip (midline variation is rare, unilateral is common)

Immunoglobulin constant region charecteristics

constant sequence crystalizable carboxyl terminal cell binding complement binding complement activating

Granulocytopoiesis

development of granulocytes (neutrophils, basophils, and eosinophils) mitotic and post mitotic phases each take a week 1. myeloblast (looks like lymphocyte) 2. promyelocyte (azurophilic with non-specific granules) 3. myelocyte (specific granules, last division stage) 4. metamyelocyte (more specific granules) 5. band/stab cells (most neutrophils) 6. mature cell

Tonsillar crypts

dense and diffuse lymphoid tissue penetrated from the pharynx, The crypts are tubules that are entered by bacteria. Movement of particles down crypts allows contact with the tonsil immune system cells There is an incomplete CT capsule surrounding the tonsil. There are efferent lymph vessels out of the tonsils but NO afferent ones.

Osteoclasts

derived from fusion of monocytes and found in shallow depressions called Howship's lacunae - areas of osteoclast activity. Osteoclasts are very large cells with 5-50 nuclei --are extensively branched -acidophilic cytoplasm -- have lots of lysosomes - acid phosphatase reaction -- have lots of mito, well dev RER and Golgi contact is : ruffled border - plasma membrane infoldings and clear zone ( abundant microfilaments) that demarcates bone area to be resorbed Resorption in 2 phases: extracellular activity 1.initial dissolution of Ca salts by organic acids from PM 2. Subsequent enzymatic degradation of collagen by lysosomal enzymes (collagenase, proteolytic enzymes)

CO2 export

exported via carbamate on amino terminus, also hydration of CO2 via carbonic anhydrase. Exchange of Cl- in tissues so CO2 becomes HCO3-, later in lungs Cl- pumped out and HCO3- becomes CO2 and is exhaled.

C-reactive protein

first to rise in acute infection, binds phosphocholine on bacteria cell walls acting as opsonin and causing activation of complement, may lead to heart attacks

Pluripotent

has blastocyst inner cell mass, can become all cell types except extra-embyonic cells or tissues. Hematopoietic stem cells gives rise to all three cell types of formed elements of blood.

Osseous ring

held together by Sacroiliac joint (plane joint great shear stress: fibrous cartilage) and pubic symphysis (synchondrosis - almost proper joint)

Spectrin

helps RBCs move through small vessels via folding

Gamma-Glutamyltransferase (GGT)

hints at liver and bile duct problems, higher amount in males causes of high GGT: induction of enzyme synthesis, by detoxification of drugs and alcohol by the gamma-glutamyl cycle in liver Anticonvulsants, phenobarbitone and alcohol induce proliferation of the endoplasmic reticulum releasing GGT, Cholestatic liver disease:hepatocellular damage

Elastic Cartilage

identical to hyaline cartilage except that its matrix and perichondrium also contain elastic fibers. Fibers are stained by resorcin- fuchsin and orcein Location: pinna of ear, external and internal auditory tubes, epiglottis, larynx

Reticular (Adventitial) cells

in stroma: form hemopoietic cords and secrete reticular fibers of collagen type III, they also secrete cytokines that stimulate progenitor cells to become RBCs.

Lymphocytes

include B cells, T cells, and null cells: stem cells and natural killer cells. Only leukocyte to return to blood from tissue (large lymphocytes.) (Small is 8um, Medium is ~10um, large is 10+um) Cytoplasm contains few azurophilic but no specific granules.

Epistasis/ Modifier Genes

interaction between non-allelic genes, might be the underlying reason for reduced penetrance in some diseases Ex) hh person has blood type O (subtype Oh) even if she has genotype AB in the ABO system RBCs for transfusion usually in saline not serum

Skin layers (general)

keratinized epiderm (ectoderm, avascular) and dermis (mesoderm). Hypodermis not a true layer but has fat. Epidermis has pegs that attach to dermal papillae (blood vessels). Thick/thin classification based on epidermis. Keratinocytes begin life at the bottom layer; as they move up they cease dividing, differentiate, die, and are finally sloughed off (desquamation) Keratin intermediate = tonofilaments

Arteries of scalp and face

large anastamoses, injury may lead to death via bleeding out. Scalp injury: Apply pressure Ophthalmic artery derivatives only ones from internal carotid

Monocytes

largest blood cell, member of the mononuclear phagocyte system (differentiation depends on surrounding tissue type). They phagocytose and destroy dead and defunct cells as well as antigens and foreign particulate matter. Contain many azurophilic but no specific granules. They are precursor cells to macrophages

Interleukins (cytokine family)

largest group that communicates between WBCs IL-1 paragenic IL-2 autocrinic on B cells IL-4 (with 5) IG production of B cells IL-6 Liver MBL/ CRP IL-10 anti-inflammatory IL-12 leads to TH1 (lesser form of leprosy)

Platelet count

low: thrombocytopenia

Albumin

main functions: oncotic pressure, transport of drugs and organic compounds low levels bad in patients taking drugs

Skin (innate immunity)

main physical barrier antimicrobial secretions (fatty acids in sweat; sebaceous gland) chemotactic secretions: TNF-a, IL-8, etc. antigen presentation by dendritic cells tight junctions at all locations

Accessory proteins in sarcomeres

maintain precise alignment of thin and thick filaments. Spacing, attachment and alignment

Osteocytes

mature bone cells derived from osteoblasts that became trapped in lacunae within the calcified matrix (about 30,000/mm3 - radiating from lacuna are canaliculi (tunnel-like spaces) that house cytoplasmic processes of osteocytes - gap junctions form between ends of processes allowing movement of ions and small molecules - extracellular fluid (nutrients & metabolites) are found within canaliculi - are flat, almond shaped cells with reduced RER & Golgi - are involved in maintenance of bone matrix by maintaining blood calcium levels - death of these cells result in resorption of matrix

Monocytopoiesis

monocytes and neutrophils share the same progenitor (GFU-GM) 1. Promonocyte: cytoplasm is bluish and houses numerous azurophilic (non-specific) granules (lysosomes) 2. Monocyte: newly formed monocytes enter the connective tissue spaces of the body and transform into macrophages may divide again (unlike granulocytes)

MALT

mucosa-assoc. lymphatic tissue (diffuse lymphatic tissue) 2 major types of MALT 1) Bronchus-associated lymphoid tissue (BALT) 2) Gut-associated lymphoid tissue (GALT) may also form lymphoid nodules (aka lymphoid follicles), which are dense aggregations of lymphocytes arranged as spherical, unencapsulated clusters

The Respiratory Tract (innate immunity)

mucus ciliated epithelium the cough-sneeze reflex surfactants (collectins): secreted by type II pneumocytes lubrication of the alveoli: binds pathogens for phagocytosis alveolar macrophages

Muscle terminology and classification

muscle cell= muscle fiber Cytoplasm of the muscle fiber = sarcoplasm Muscle fiber cell membrane = sarcolemma Smooth endoplasmic reticulum of the muscle fiber = sarcoplasmic reticulum Classification based on function and structure, all muscle is developed from mesoderm except dilator/constrictor pupillae (neuroectoderm)

Red Blood Cells: Hb & Carbonic Anhydrase

must preferentially bind O2 at lung, must release O2 at tissues, transports CO2 to lung from tissue, must preferentially capture CO2 at tissues= removes acidity from tissues, Hb and carbonic anhydrase work together, RBC's do not consume the oxygen they carry, O2 freely exchanged across membranes

General properties of complement systems

normal serum proteins (10%) about 34 components required for cytolysis occur as zymogens heat labile - destroyed at 56C, 30´ fixed in ag.ab reactions activity is generally non specific production slightly increased following infection activation by several pathways

Cancer: Transcription factors as oncogenes (14 and 8 chromosome switch of c-fos/ c-myc) ($$)

normal: c-Fos and c-Myc stimulate transcription of genes encoding proteins that promote progression through G1 phase and G1 to S transition. Usually quickly broken down due to instability of DNA Burkitt's lymphoma: c-myc gene translocated to chr 14, bringing it from distant chromosomal location to enhancer of antibody genes. Translocated myc gene, now with the antibody enhancer, is continually expressed, causing B cell to become cancerous. Localized duplication of DNA containing the myc gene also causes high expression of the otherwise normal Myc protein.

Neutrophil Extracellular Traps (NETs)

novel structures formed by activated neutrophils can disarm and kill bacteria before they reach host cells, distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. NETs use granules and lysosome to kill trapped bacteria (more killed via NETs then phagocytosis).

Muscles of SCALP and FACE

orbicularis oculi muscle: orbital part tightly shuts eye, palpebral part is a light closure during blinking Risorius: wide smile platysma: frowning mentalis: pouting buccinator: sucking The superior tarsal muscle is attached to the levator palpebrae m., that aids in elevating the eyelid (Damaged in Horner's causing ptosis)

Transient cells

originate mainly in the bone marrow and circulate in the bloodstream, upon receiving the proper stimulus they leave the bloodstream into the connective tissue (diapedesis). Include: Plasma cells, Lymphocytes, Neutrophils, Eosinophils, Basophils, Monocytes and Macrophages

Myoglobin

oxygen storage in muscle, heme and globin dissociate with detergent (hydrophobic bonds), The rate of O2 diffusion from capillaries to tissue is slow because of the solubility of oxygen. Myoglobin increases the solubility of oxygen so myoglobin facilitates oxygen diffusion. Binds hyperbolicaly (greater attraction to O2 and not controlled). Better binding of O2 is so tissues do not lose needed O2.

Complement system organization

recognition unit: C1q, C1r, C1s activation unit: C3 convertase (C3 is essential and most abundant) membrane attack complex (MAC): C5bC6C789

Sinusoid capillaries

red dotted, contains erythrocytes

HOX gene

regulates the patterning developments of head and neck in humans, the most typical feature in development of head and neck is formed by the pharyngeal (branchial) arches. Five pairs of pharyngeal arches form on either side of the pharyngeal foregut, starting on day 22 in craniocaudal sequence during the 4th and 5th weeks.

erythropoietin

secreted mainly by kidneys in adults and by the liver in the fetus: adjusts RBC production to match O2 demand.

Basophils

several surface receptors on plasmamembrane, including (IgE) receptors, the specific granules contain heparin and histamine. Mediators (hist, leuktrienes) released deal with anaphylactic shock and increase blood flow to infected area. Tell basophils and mast cells apart by location (blood is basophil, CT is mast cell)

Germinal centers

sites within secondary lymphoid where mature B lymphocytes proliferate, differentiate, mutate their antibodies and switch the class of their antibodies during a immune response. The germinal center contains B-cells that have differentiated into antibody secreting plasma cells. The plasma cells have much more volume of cytoplasm then lymphocytes which stains lightly. Germinal centers can rapidly grow and develop in a day or two after exposure to antigen. Primary lymphoid nodules do not have a germinal center!

Peripheral blood smear (PBS) ($)

size, color, abnormal shape, inclusion bodies

The Gastrointestinal Tract (innate immunity)

stomach acidity resident bacteria epithelium Paneth cells - secrete a-defensins, lysozyme and phospholipase-A

Hassall's or thymic corpuscles

structures found in the medulla of the human thymus A rounded globular mass of cells, formed from ERCs Pretty much a graveyard for necrotic T cells

Azures

substances formed when methylene blue is oxidized, The lysosomes (primary granules) of all leukocytes stain "azurophilic". Compounds that bind to azures are stained reddish-blue.

Complement system: alternative pathway ($)

usually first to be activated. C3b is an opsonin. Activation: by pathogens/ non-self Properdin, a promoter - stabilizes C3bBb Factor H, an inactivator - dissociation of C3bBb Decay accelerating factor (DAF) action similar to Factor H Factor I, an inactivator of C3b

Platelets (post-clotting)

vessel repair is aided by platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta): promote invasion of fibroblasts. Local application through Platelet-rich plasma (PRP) is an adjunct to wound healing. Clot is dissolved by plasmin.

Defecation

via puborectal muscle, pelvic floor hiatus becomes smaller during squeeze and larger during defecation. vertical movement of the anus, and flattening of the levator plate with squeeze

Iron functions

• Hemoglobin/Myoglobin - oxygen transport to tissues. Reduced function results in erythropoeitin activation of erythrocyte production. [Fe+2-heme] • Cytochrome P450's - detoxification (eg drugs), and other oxidative reactions involving oxygenase activities in endoplasmic reticulum. • Cytochromes a, b, and c of mitochondrial electron transport for energy generation (ATP). • Aconitase and other iron-sulfur complex enzymes [Fe+3 clusters with Cys-ligands] • Oxidases and lysosomes and peroxisomes - catabolism IRE 'sense' iron content in cells and adjust the amount of cellular uptake accordingly C-aconitase is the intracellular master regulator of iron homeostasis