(fibrin stabilizing factor) which is activated by thrombin creates fibrin network, forms permanent clot at the injury site

Fibrinolysis is activated by plasma protein plasminogen, the clot itself releases the plasminogen activator.

ANTICOAGULANTS: Fibrin (keeps thrombin from spreading), antithrombin III, heparin (prevents activation of factor 9), protein C and protein S which are vitamin K dependent. (Protein C and S are endogenous).

Musculoskeletal Physiology

Skeletal Muscle: many parallel myofibers, each with a multinucleated structure surrounded by the sarcolemma.

-shortening of muscle occurs from extent of thin-thick filament overlap. (sliding filament mechanism) Sarcolemma shortens, but fibers remain the same size.

Contraction:

ATP in the cytoplasm replaces the previously bound ADP, resulting in the dissociation of the myosin head, after hydrolysis of ATP, the potential of energy remains in the myosin head.

-If ATP runs out, then remain in a rigor state, leads to inability of myosin head to be released.

Action potential from depolarization caused by Ach binding, is transmitted down a T-tubule to the sarcoplasm reticulum, releasing Ca2+ into the cytoplasm into the myofibrils and binds to the TnC subunit of Troponin and causes a conformational change and moving TROPOMYOSIN with respect to actin.

-once the tropomysin goes out of the way, myosin ATPase can be activated, and thick and thin filaments past each other.

-succinylcholine can inhibit Calcium re-uptake by the ryan-odine receptor causing muscles to overcontract.

Isometric contraction: occurs when both ends of a muscle are fixed and no change in length occurs, but TENSION increases.

Isotonic contraction: occurs when a muscle shortens during contraction while tension remainds constant.

Most physical activity includes borth isometric and isotonic contractions. (dynamic) Sarcomeres of the same myofibril do not generate additive force, to generate more force more muscle fibers must be recruited.

Fast-twitch fibers are white, large in diameter, with few muscle fibers per unit, it has a absence of red myoglobin (appears white), it has many sarcoplasm reticulum, myosin ATPase but FEW mitochondria because use anaerobic glycolysis. FINE MOVEMENTS Slow-twitch fibers are red because of presence of myoglobin. Smaller in diameter, less sarcoplasm reticulum and fewer T-tubules than white muscle, used for sustained

contractions, oxidative metabolism is used for energy, so need many mitochondria.

Motor units are all muscle fibers that are inntervated by a single nerve axon (alpha motor) -must be same muscle type, if neuron is dystroyed, associated muscles atrophy.

Tetanus is the summation of contractions when the fibers are stimulated repetitively with a short time, resulting in greater contractions than from a single twitch.

Graded forces increase the number of motor units and increase the firing rate to increase muscle tension (force).

Muscle receptors: Two types, muscle spindles and Golgi Tendon Organs

Muscle spindles: intrafusal fibers that are innervated by small neurons called gamma motor neurons which terminate at the nuclear bag fibers

-Ia fibers innervate the nuclear bag and nuclear chains (intrafusal muscle fibers) -secondary slower conducting type II fibers innervates only the nuclear chain fibers

Muscle stretch of the muscle spindle afferents activates alpha motor neurons to activate extrafusal fibers of the muscle spindle to cause muscle contraction.

Golgi Tendon organs afferent fibers fire in response to stretch and lengthening and are in series with extrafusal muscle fibers and are supplied by Ib afferent fibers. Excessive stretch of muscle causes inhibitory internuerons to synapse on alpha motor neurons

-tendon organs sense muscle TENSION, while muscle spindles sense MUSCLE LENGTH!

Smooth muscle: is generally smaller and usually uninucleated.

-fewer myofibrils, less organized

-DENSE bodies: on the cell bodies similar to Z lines -less myosin/thick filaments

-no T-tubules, sparse sarcoplasm reticulum. DOES NOT HAVE TROPONIN, instead calcium binds to myosin kinase to mediate excitation of muscle.

Contraction occurs when thin filaments inserted into the dense bodies are pulled close together by bridging myosin units.

Stretch reflex: MYOTATIC REFLEX, responds to passive stretch of muscle (1a afferent)

Mitosis:

G1: growth and preparation of the chromosomes for replication S: synthesis

G2: preparation for mitosis

M: mitosis (no synthesis, only division)

IgG: most common antibody, passes placenta and enters fecal circulation IgA: second most abundant

IgD: receptor site for B-lymphocytes

IgM: does not past placenta, first antibody into circulation

IgE: basophils, mast cells, allergic and anaphylactic type I reacition hypersensitivity.

Hypertonic: higher salt concentration, water goes in Hypotonic: lower salt concentration, water leaves.

Urea cycle

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The reactions of the urea cycle.

The color scheme is as follows: enzymes, coenzymes, substrate names, inorganic molecules, Asp and urea's nitrogen that comes from it, NH₄⁺ and urea's nitrogen that comes from it, HCO₃^- and urea's carbon that comes from it

The urea cycle, also known as the ornithine cycle, is a cycle of biochemical reactions occurring in many animal organisms that produces urea from ammonia (NH₄⁺). This cycle was the first metabolic cycle discovered (Krebs and Hensenleit, 1932).

Contents

[hide]

 1 Function

 2 Reactions

 3 Regulation o 3.1 NAcGlu

o 3.2 Substrate concentrations

 4 See also

 5 External links

[edit]

Function

Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like urea or uric acid, which are much less toxic. Insufficiency of the urea cycle occurs in some genetic disorders (inborn errors of metabolism), and in liver failure. The result of liver failure is

accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic encephalopathy.

[edit]

Reactions

The urea cycle consists of five reactions - two mitochondrial and three cytosolic. The cycle converts two amino groups, one from NH₄⁺ and one from Asp, and a carbon atom from HCO₃^-, to relatively nontoxic excretion product, urea, at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP). Orn is the carier of these carbon and nitrogen atoms.

Reactions of cycle:

Step Reactant Product Catalyzed by Location

1 2ATP + HCO₃^- + NH₄⁺ carbamoyl phosphate + 2ADP + P_i CPS1 mitochondrial

2 carbamoyl phosphate + ornithine citrulline + P_i OTC mitochondrial

3 citrulline + aspartate + ATP argininosuccinate + AMP + PPi ASS cytosolic

4 argininosuccinate Arg + fumarate ASL cytosolic

5 Arg + H₂O ornithine + urea ARG1 cytosolic

Summary reaction:

 2 NH₃ + CO₂ + 4 ATP + aspartate → urea + fumarate + 4 ADP + 4 P_i

[edit]

Regulation

Alternate representation of urea cycle. Numbering is different from that presented above. Aqua oval is mitochondrion. CPS1 not displayed.

[edit]

NAcGlu

The synthesis of carbamoyl phosphate and the urea cycle are dependent on the presence of NAcGlu, which allosterically activates CPS1. Synthesis of NAcGlu by NAGS, is stimulated by Arg - allosteric stimulator of NAGS, and Glu - a product in the transamination reactions and one of NAGS's substrates, both of which are elevated when free amino acids are elevated. So, Arg is not only a substrate for the urea cycle reactions but also serves as an activator for the urea cycle.

[edit]

Substrate concentrations

The remaining enzymes of the cycle are controlled by the concentrations of their substrates. Thus, inherited deficiencies in the cycle enzymes other than ARG1 do not result in significant decrease in urea production (the total lack of any cycle enzyme results in death shortly after birth). Rather, the deficient enzyme's substrate builds up, increasing the rate of the deficient reaction to normal.

The anomalous substrate buildup is not without cost, however. The substrate concentrations become elevated all the way back up the cycle to NH₄⁺, resulting in hyperammonemia (elevated [NH₄⁺]_P).

Although the root cause of NH4+

toxicity is not completely understood, a high [NH4+

] puts an enormous strain on the NH₄⁺-clearing system, especially in the brain (symptoms of urea cycle enzyme deficiencies include mental retardation and lethargy). This clearing system involves GLUD1 and GLUL, which decrease the 2OG and Glu pools. The brain is most sensitive to the depletion of these pools. Depletion of 2OG decreses the rate of TCAC, whereas Glu is both a neurotransmitter and a precursor to GABA, another neurotransmitter. [1](p.734)

PKU: phenylalanine hydroxylase

-deficiency in phenyalanine hydroxylase causes buildup of phenylalanine in the bloodcauses mental retardation

Cystic fibrosis, sickle cell anemia, down syndrome know main things happening -cystic fibrosis: diagnosis involves finding increased amounts of sodium chloride in sweat; mechanism involves blockage of Cl- ion transporter in epithelial cell

membranesviscous secretions

-sickle cell anemia: single amino acid replacement in beta-chain (substitution of glutamate in position 6 with valine)causes crescent shaped RBCs. Low oxygen or dehydration precipitates sickling. An advantage is that heterozygotes are relatively malaria resistant. Homozygotes may be subjected to complications such as aplastic crisis (from B19 parvovirus infection), autosplenectomy, increased risk of encapsulated

organism infection, Salmonella osteomyelitis, painful crisis (vaso-occlusive), and splenic sequestration crisis.

-down syndrome: trisomy 21lower than average cognitive function, ―simian crease‖, heart/gastroesophageal defects

Protein hormones and lipid hormones difference and how they bind: vitamin D is both a steroid and it does regulation of calcium, it binds to intracellular receptor bc it’s a steroid hormone

-Lipid/steroid hormones cross the cell membrane and bind to specific cytosolic or nuclear receptors. These receptor-hormone complexes accumulate in the nucleus and bind to regulatory DNA sequences causing stimulation of inhibition of gene transcription.

The precursor for steroid hormones is cholesterol. They are primary produced by the adrenal cortex and the gonads as well as the placenta during pregnancy.

*note: D Vitamins are a group of sterols with hormone-like functions

-Protein/peptide hormones are produced like regular proteins in an inactive form known as a preprohormone which is cleaved to form prohormones by enzymes in the RER. This prohormone is then packaged in the golgi for transport outside of thecell via exocytosis.

Most peptide hormones serve as neurotransmitters and therefore bind to catalytic or G-protein coupled receptors on target cells (they are too hydrophilic and large to just diffuse through the plasma membrane).

Ehler’s donlons disease:

Ehler’s Danlos syndrome (EDS) is the name given to a group of inherited disorders that involve a genetic defect in collagen and connective tissue synthesis and structure. This results in fragile and hyperelastic skin, unstable and hyperextensible (hypermobile) joints, and fragile tissue and blood vessels. A genetic defect causes reduced amounts of collagen, disorganization of collagen that is usually organized into bundles, and

alterations in the size and shape of collagen. There are six subtypes of EDS classified according to clinical features.

Staph and strept for micro: anaerobes, read micro made for staph and strept Staph aureus:

-Protein A (virulence factor)

-causes: inflammatory disease (skin infxn, organ abscesses, pneumonia) and toxin-mediated disease

-gram positive (food poisoning, toxic shock syndrome, scaled skin syndrome) -coagulase positivecauses clumping for abscess formation

Strep pyogenes (Group A):

-beta-hemolytic

-causes: pyogenic (pharyngitis, cellulites, impetigo), toxigenic (scarlet fever, TSS), immunologic (rheumatic fever, acute glomerulonephritis) diseases

-bacitracin sensitivity

-antibody to M protein enhances host defense -spread by respiratory route/close contact

Lateral ling swelling ant 2/3 of tongue bifid tongue

-also known as cleft tonguedivided in its anterior part by a longitudinal fissure Facial expression is branchial arch 2

-involves these muscles: muscles of facial expression, posterior belly of the digastric, stapedius, and the stylohyoid

-Bones, ligaments, cartilages: Reichert’s Cartilage, stapes, styloid process, stylohyoid ligament, upper part and lesser horn of the hyoid.

Arm innervation for arms, thumb, lymph nodes ARM

Flexors:

Coracobrachialis- musculocutaneous nerve (C5, C6, C7) Biceps brachii- musculocutaneous nerve (C5, C6)

Branchialis- musculocutaneous nerve (C5, C6) and small contribution by radial nerve to lateral part of muscle

*note: musculocutaneous nerve provides motor innervation to all muscles in the anterior compartment of the arm and sensory innervation to the skin on the lateral surface of the forearm.

Extensor:

Triceps brachii- radial nerve (C6, C7, C8)

Thumbthenar muscles are innervated by the recurrent branch of the median nerve

Five lymph groups that drain the upper limb:

Humeral (lateral) nodes Pectoral (anterior) nodes Subscapular (posterior) nodes

Central nodes (embedded in axillary fat) Apical nodes (most superior group)

Vitamin k is gamma carboxylation

-contained in cabbage, cauliflower, spinach, egg yolk, and liver -also synthesized by gut bacteria

-required for hepatic synthesis of prothrombin, factor II, VII, IX, X

-formation of clotting factors requires vitamin K-dependent carboxylation of glutamic acid residuesform a mature clotting factor that contains gamma-carboxyglutamate (Gla)

Insulin is gonna cause storage

-insulin favors uptake of glucose and other biosynthetic reactions Kaposki:H 8

Kaposi’s sarcoma caused by HHV-8 (human herpes virus) via sexual contact Oral hairy leukoplakia is Epstein barr

OHL is caused by the Epstein-Barr virus (EBV). Oral hairy leukoplakia (OHL) refers to a white patch – or white patches – that can develop in the mouth. These patches usually occur along the sides of the tongue, although they can sometimes develop on the top and underside of the tongue or along the inside of the cheek. Looking carefully at these patches, they may appear shaggy or may contain a number of tiny folds or ridges. OHL is often one of the first opportunistic infections to occur in HIV-positive people.

H. Pylori causes gastritis Interstitial pneumonia is viral

Deep lingual: tip of tongue I think we agreed on this:

-the deep lingual artery supplies the tip of the tongue

-the lingual nerve (branch of V3) provides general sensory innervation to tip -chorda tympani provides taste fibers to the tip

Brachial plexus question

Brachial Plexus (from medial to distal):

Roots (anterior rami of spinal nerves C5, 6, 7, 8, and T1) Trunks (superior, middle, inferior)

Divisions (anterior and posterior of each trunk) Cords (lateral, posterior, and medial)

Branches

Nucleus solitarius: taste

Chemoreceptors and baroreceptors inputs reach the nucleus solitarius bringing and processing sensory visceral inputs to cranial nerve nuclei of X and IX (eg. from the carotid body and sinus) via the solitary tract.

The nucleus solitarius also processes taste afferents. These visceral sensory inputs enter at the medullary level to reach the solitary tract nucleus from VII (ant 2/3 portion of tongue), IX (posterior 1/3 of tongue), and X (back of throat, including the

epiglottis). Some somatic input (eg. touch) also travels in through these nerves to terminate in the spinal trigeminal nucleus. It is also interesting to note that the nucleus solitarius collaborates with the reticular formation and is the major sensory component of the medullary respiratory center and of the ill-defined cardiovascular center.

Tumor of infancy: hemangioma

-an extremely common benign tumor, occurring most commonly in infancy and

childhood, made up of newly formed blood vessels, and resulting from malformation of angioblastic tissue of fetal life. There are two main types: capillary and cavernous. 2. a general term denoting a benign or malignant vascular tumor that resembles the classic type of hemangioma but occurs at any age.

Hodgkin’s and non-hodgkin’s

Hodgkin's lymphoma is a malignancy (cancer) of lymph tissue found in the lymph nodes, spleen, liver, and bone marrow. The first sign of this cancer is often an enlarged lymph node which appears without a known cause-extranodal is rare. The disease can spread to adjacent lymph nodes and later may spread outside the lymph nodes to the lungs, liver, or bone marrow.

*Presence of Reed-Sternberg (RS) cells: giant histiocytic cells, typically multinucleate, most often binucleate with the two halves of the cell appearing as mirror-images of each other; the nuclei are enclosed in abundant amphophilic cytoplasm and contain prominent nucleoli. The presence of the cells is the common histiologic characteristic of Hodgkin's disease.

The cause is not known. The incidence is 2 in 10,000 people. Hodgkin's lymphoma is most common among people 15 to 35 and 50 to 70 years old. Symptoms:

 Painless swelling of the lymph nodes in the neck, armpits, or groin (swollen glands)

 Fatigue

 Fever and chills

 Night sweats

 Weight loss

 Loss of appetite

 Generalized itching 50% cases associated with EBV

Non-Hodgkin's lymphomas are cancers of lymphoid tissue (lymph nodes, spleen, and other organs of the immune system). Non-Hodgkin's lymphomas can be slow-growing (low-grade) or rapidly growing (high-grade) cancer. For most patients, the cause is unknown, but lymphomas may develop in people with suppressed immune systems as a result of organ transplantation or HIV, for instance.

It is characterized by multiple peripheral nodes with common extra-nodal involvement without spreading. Usually involves Bcells and occurs in persons age 20-40 yrs.

Five Types:

Small lymphocytic lymphoma (occurs mainly in adults and affects B cells)

Follicular lymphoma (occurs mainly in adults and affects B cells; genetic mutation bcl-2)

Diffuse large cell (usually occurs in older adults with 20% in children80% B cells and 20% T cells)

Lymphoblastic lymphoma (occurs most often in children and affects immature T cells) Burkitt’s lymphoma (occurs most often in children and affects B cells; genetic mutation c-myc)

Symptoms:

 Enlarged lymph nodes (such as an armpit lump), isolated or widespread

 Fever

 Excessive sweating, with night sweats

 Unintentional weight loss

What is this cross section of brain: saw ventricles and pons and midbrain saggital?

Tunica intima, media and adventitia, what’s in each and the composition;

-Tunica intima is composed of a lining layer endothelium that sits on the basal lamina.

-Tunica media is the middle layer and is composed predominantly of smooth muscle reinforced by organized layers of elastic tissueelastic laminae; very prominent in arteries.

-Tunica adventitia is collagen and loose CT but smooth muscle cells may be present;

most prominent in veins.

Tympanic membrane is lateral wall of ear Boundaries of the middle ear cavity include:

-Roof (tegmental wall) -petrous part of temporal bone

-Floor (jugular wall)-separates space from internal jugular gein -Lateral (membranous wall)- tympanic membrane (mostly)

-Posterior (mastoid wall)-lower part consists of bony partition between tympanic cavity and mastoid air cells; upper portion is continuous with aditus to the mastoid antrum -Anterior wall-lower part is thin later of bone separating tympanic cavity from internal carotid artery; superior wall containing opening for entrance of pharngotympanic tube and opening for tensor tympani muscle; this is also where chorda tympani exits.

Middle ear is what part of temporal bone? Petrous is inner and tympanic is middle -Arcuate eminence (rounded protrusion near superior ridge of the petrous part of the temporal bone) lies right over the anterior semicircular canal of the inner ear.

-Tegman tympani (depression that is anterior and lateral to arcuate eminence) is thin bony roof above middle ear cavity.

Alpha fetoprotein- tumor marker for hepatocellular tumor?

AFP normally made by fetus detected in amniotic fluid. Increased amounts is tumor marker for hepatocellular carcinomas and neural tube defects as well as Edward’s syndrome (trisomy 18).

What is found in striated ducts?

cytoplasm with basophils

lots of granules in the apical portion Know boundaries of temperatures

Autoclaving 250 F (121 C) for 15-20 minutes

Dry heat 320 F (160 C) for 2 hours or 340 F (170 C) for 1 hour

0.3% glutaraldehyde is best used as a?

a. Immersing agent (usually 2% is used for 10 hours)

b. disinfectant for inanimate surfaces because 0.3% is too dilute?

Which cleaning agent has the broadest spectrum of cleaning?

ethanol

isopropyl alcohol others (iodine?)

What is best for lipophilic and lipophobic substances?

Lipophilicuse cationic detergents Lipophobicuse anionic detergents

In wound healing, myoepithelial cells come from or do what?

from stiated muscles smooth muscles

help to bring wound together Bone metastasizes to liver?

Things that metastasize to the liver: Colon>Stomach>Pancreas>Breast>Lung (Cancer Sometimes Penetrates Benign Liver)

Things that metastasize to bone: Breast, Lung, Thyroid, Testes, Kidney, Prostate (BLT with a Kosher Pickle)

-metastases from breast and prostate are most common What is found in the deep dermis?

Deep dermis…maybe she means hypodermis since that’s the layer below the dermis.

The hypodermis contains:

 loosely arranged elastic fibres

 fibrous bands anchoring skin to deep fascia

 fat:

o absent in eyelid, scrotum, penis, nipple and areola

o distribution is a secondary sexual characteristic: it forms the breasts of females and accentuates the contour of female hips

 blood vessels on route to dermis

 lymphatic vessels on route from dermis

 hair follicle roots

 the glandular part of some sudiferous glands

 nerves:

o free endings

o Panicinian corpuscles

 bursae: only in the space overlying joints in order to facilitate smooth passage of overlying skin

 sheets of muscle: panniculus carnosus

What is not found in the pulp?

Lipocytes (these are fat-storing stellate cells of the liver) lymphocytes

undifferentiated mesenchymal tissue collagen

Lots on what drains into which lymph node (submandibular, submental, deep cerivical) -lymphatics from the submandibular and sublingual glands drain mainly into the

submandibular nodes and then into deep cervical nodes

submandibular nodes and then into deep cervical nodes

In document NBDE (Page 85-147)