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of tissues
-heparan sulfate: basement membranes
GAGS: repeating disaccharides, highly negatively charged.
Glucose Proteins (GLUT):
GLUT1: red blood cells, Blood brain barrier
GLUT3: nuerons
GLUT4: skeletal muscle and adipose, regulated by INSULIN
GLUT2: Liver, low affinity, high Km, high Vmax - not saturated, GLUCOKINASE
S-GLUT: kidney/intestine Na/Glucose transport
GLUT5: transports fructose into the intestestine and testis.
Glycolysis:
Glucose PFK-Glucose 6P ISOMERASE - Fructose 6P Fructose 16P, -ALDOLASE(DHAP, G3P), DHAP becomes G3P by triose isomerase,13BPG, 23BPG ENOLASE
(inhibited by NaF) - PEP, 2 pyruvate.
PFK-1: rate limiting step of glycolysis, make f6p-f1,6p.
PFK-2: Makes f2,6P in liver, which activates glycolysis and inhibits
gluconeogenesis/bisphosphatase).
1,3BPG and PEP produce ATP.
G3P to 1,3BPG uses dehydrogenase to make NADH.
Pyruvate kinase deficiency: causes a decrease in ATP production in RBC causing lysis
because of Na/K ATP dependent transport.
Pyruvate can be converted to lactate and alanine in the cytosol by transaminase.
Pyruvate dehydrogenase is irreversible there is no enzyme in humans that will reverse
this reaction. Five coenzyme are involved, thiamine pyrophosphate (E1), lipoic acid,
coenzyme A (E2), FAD, NAD (E3),
-Thiamine defieciency causes lactic acidosis, because no dehydrogenase.
-INACTIVATED BY PHOSPHORYLASE, INSULIN ACTIVATES PHOSPHATASE.
Three rate limiting steps: hexokinase (glucokinase), PFK, pyruvate kinase.
Gluconeogenesis:
Occurs mainly in the liver and kidney, (NOT IN MUSCLE, because doesnt have
pyruvate carboxylase).
Comes from lactate (in RBC-does not have oxidative mitochondria, and anaerobic
muscle), glycerol (fat), and AA (skeletal muscle).
Pyruvae kinase reverse reaction: PEPCK(and GTP) and pyruvate carboxylase/biotin.
Other enzymes: FBPase-1 (inhibited by F26P), G6Pase (deficiency causes Von-Gierkes
disease).
Overall reaction requires 6 ATP (4 for pyruvate to PEP and 2 for 3PG to 23PG).
Cori Cycle: Pyruvate lactate in RBC and skeletal muscle, the the lens of the eye,
medulla of kidney, testes, and leukocytes.
Glucogenic amino acids: can be converted to intermediates of TCA or glycolysis
Includes all except Lysine and Luecine which are ketogenic.
-essential fatty acids cannot be made by humans because lack enzyme to place
double bonds at certain positions (omega 3 and omega 6)
Ketone bodies: acetone, aceoacetic acid and B-hydroxybutyric acid, produced from fatty
acids and AA during starvation and diabetic ketoacidosis. They are excreted from the
urine, produce a fruity breath odor (also in diabetics type I).
Phospholipids: Ethanolamine cephalin, choline lecithin.
Sphingolipids & glycolipids contain ceramide composed of sphingosine.
Lipoproteins: Contain hydrophilic shell (phospholipid) and hydrophobic core
Chylomicrons: least dense, TAG and cholesterol ester, in smooth ER of intestinal cells
-apo B48 is unique to chylomicrons, apo E faclilitates chylomicrons to liver
VLDLs: higher density than chylomicrons, can produce IDLs
LDLs: generated from VLDLs and IDLs, transports cholesterol to extrahepatic tissues by
endocytosis. Disease is called familial hypercholesterolemia, insuffiency of LDL
receptors.
HDL: synthesized by the liver, they are a circulating resoivior for apoproteins, remove
cholesterol from tissues back to the liver.
LCAT: esterifies HDL cholesterol, reverse cholesterol transport
Apo D: transfer esters to VLDL and chylomicrons.
Fatty Acid synthesis: acetyl-CoA, bicarbonate, and NADPH. (Citrate has + effect)
Occurs in the cytosol, oxidation occurs in the mitochondria
Citrate shuttle is used to carry acetyl-CoA from the mitochondria to cytosol.
-citrate can be broken down to acetyl coa and oxalaocetate, and can produce
NADPH.
Acetyl-CoA carboxylase: biotin and bicarbonate produces malonyl-CoA. Uses 1 ATP.
- rate limiting enzyme
Fatty acid synthase: adds 2 carbons to the carboxyl end with ACP protein. It is
repeated until pamitoyl-CoA (16 Carbon) is produced (palmitoyl-CoA inhibits the HMP
shunt). Uses 2 NADPH, total process uses 7 ATP and 14 NADPH.
Glucagon (remember phosphorylation) inactivates synthase by phosphorylating it.
Coenzyme A used in fatty acid synthesis and metabolism.
Malonyl CoA is in synthesis but not breakdown of fatty acids.
Fatty Acid Oxidation: occurs in peroxisomes and mitochondria
Fatty acyl-CoA synthase driven by pyrophosphate.
Carnitine shuttle includes CAT I and CAT II to transport fatty acyl CoA into
mitochondria. (CAT I is rate-limiting enzyme)
Inhibited by malonly-CoA
Produces 1 acetyl CoA, 1 FADH2 and 1 NADH = 5 ATP
So palmitic acid (C16) produces 8 acetyl CoA, 7 NADH, 7 FADH2
Odd carbon fatty acids are carboxylated to methylmalonyl-CoA which with vitamin B12
becomes succinly CoA into the TCA.
Ketone Body formation: Acetoacetatic and B-hydroxybutyric acids.
PHYSIOLOGY:
Gastrointestinal:
Feeding center is in the lateral hypothalamus, satiety center is in the ventromedial nucleus
of the hypothalamus (glucostats)
CCK receptors in brain to reduce apetite when stimulated. (calcitonin can also decrease
appetite)
Salivary composition (hypotonic): Na and Cl are reabsorbed, and K+ and HC03 are
secreted so saliva is alkaline. Resultant saliva is hypotonic because more ions are
reabsorbed, when high parasympathetic stimulation the osmolarity of saliva is equal to
plasma.
Enzymes: lingual lipase, ptyalin(amylase)
Beta-amylase: converts starch to maltose and dextrins
Alpha-Amylase: increase with sympathetic sys, hydrolyzes a14 glycosidic link
Other: lactoferrin, mucin, proline proteins for enamel protection, kallilkrein which
cleaves kinogens to form bradykinin. ->> increase blood flow to increase salivary flow.
Swallowing: Nucleus of solitary tract (CN9 & 10) mediated by nucleus ambiguous and
hypoglossal nucleus. OCCURS about 600x a day. (1/3 eating, mostly during rest)
Upper esophageal sphincter: relax when swallow, contract when preventing
reflux. Vomiting is stopped by contraction of the UES.
Lower esophageal sphincter: relax on swallow, phrenicoesaphogeal ligament, gastrin
increases tone, while secretin and CCK decrease tone.
-Na and water are reabsorbed, K+ and HC03 are secreted into colon.
-relaxation of internal anal sphincter (smooth muscle) produces urge to defecate, the
external anal sphincter is skeletal muscle innervated by pudental nerve.
-CCK, gastrin and stomach distension also cause defecation.
Phases of gastric secretion:
Cephalic: smell, sight, or thought
Gastric: vagus nerve stretch reflexes
Intestinal: protein degradation in duodenum
Pancreatic secretions: H20, HC03, digestive enzymes (acinar cells)
Hepatic secretions: bilirubin, cholesterol, drugs, lipid absorption, IgA delivery
-Secretin stimulates bile high in bicarbonate.
-bilirubin is conjugated with glucuronic acid prior to secretion in bile. In large
intestine, the bilirubin is deconjugated and metabolized by bacteria.
-bile acids are synthesized from cholesterol by hepatocytes. They are conjugated
with taurine or glycine before secreted into bile.
-bile is made up of water, bile acids, cholesterol, bilirubin, and phospholipids
-KEDA vitamins require bile acid micelle to be absorbed.
Vomiting center: reticular formation of the medulla, located in the area postrema in the
floor of the fourth ventricle, stimulated by dopamine
Nervous system of GI:
Enteric nervous system:
Myenteric (Auerbachs plexus) between circular and longitudinal muscle from esophagus
to the anus
Submucosal Meissners Plexus: lies in the submucosa
Disease in nueral innervation causes Hirshsprungs disease
Vagal Parasympathetic fibers: dorsal motor nucleus of vagus in the floor of fourth
ventricle
Innervates to ascending and right transverse colon
Sacral Parasympathetic fibers: flow from S2,3,4 and innervate anorectal area, descending
sigmoid and left colon.
LES is normally contracted, and PNS relaxes the muscle.
Remember: segmentation provides mixing of chime, while peristaltic movements propel
chime along the gut.
Cardiovascular Physiology:
SA NODE AND AV NODE ARE SLOW FIBERS: Phase 0
SA Node: located at junction of SVC and right atrium, below the epicardial surface,
innervated by right vagus
AV Node: just beneath the right atrial endocardium, anterior to coronary sinus,
innervated by left vagus.
-goes onto the His Bundle where conduction is rapid
-divides to right and left bundle branch (posterior and anterior division)
BOTH INSULIN AND GLUCAGON DECREASE AA and are activated by high AA,
insulin does it by protein production and glucagon by glucose production.
Diabetes main symptoms: polyphagia (increased food consumption but weight loss),
polyuria, polydypsia (thirst), glucose in urine (normal has 0mg/min excretion)
-over 126 or 140 glucose level.
-treatment: sulfonylurea which promotes insulin action for type II diabetes.
- ketoacidosis in type I diabetes. (acute)
-chronic: retinopathy, BLINDNESS, possible amputation, kidney failure,
neuropathy, thickening of basement membranes, artherosclerosis.
RESPIRATORY PHYSIOLOGY:
Conducting airways: trachea, bronchi, bronchioles, terminal bronchioles are all part of the
anatomic dead space. (150ml)
Respiration gas exchange occurs are the respiratory bronchioles, which divide into
alverolar ducts and terminate at alveolar sacs.
Residual volume: volume of air remaining in the lungs after maximal expiration
-cannot be measure through spirometry, must use gas dilution
Tidal volume: normal breath inspired and expired
TLC (total lung capacity & functional residual capacity): cannot be measured through
spirometry, it is the maximal volume to which lungs can be expanded in inspiration
Vital capacity: maximal expiration following maximal inspiration.
Inspiratory capacity: total amount of air that can be inhaled after a NORMAL expiration.
Flow rates: FEV1 is the forced expiratory volume in 1 second, in obstructive airway
diseases FEV1/VC ratio is reduced, in restrictive lung diseases all lung volumes are
reduced so the ratio stayed the same.
Physiologic dead space: anatomic dead space plus alveolar space that is not functional,
usually due to inadequate blood supply.
-lower regions of the lung ventilate better than upper regions because the lower
alveoli are better ventilated. In lower regions of the lung the hydrostatic pressure is
higher owing to gravitational effects so flow is the greatest. In the upper region aterial
pressure can sometimes fall below arteriole pressure so there is no flow adding to the
alveolar dead space.
Diffusion is based on surfactant lining, alveolar epithelial cell, basement membrane, and
capillary endothelial cell, surface area, and ability of 02 to bind to Hb.
-CO2 has a better diffusion constant thus it diffuses much faster in the lungs and
tissues.
-CO (carbon monoxide) is limited by diffusion NOT pulmonary blood flow.
Pulmonary veins terminate in a FOUR-vein hilum into the left atrium, and travel with
bronchi through the centers of the primary lobules of the lung until they reach the
terminal bronchioles.
Pulmonary circulation: low resistance, very low pressure gradient, pulmonary artery
pressure is much lower than mean arterial pressure (100), the flow rate is identical
because the two circulations are in series.
-when alveolar o2 decreases or c02 increases, pulmonary vessels constrict
because they divert blood away from poorly ventilated areas of the lung where low 02
concentrations are found and ensures better circulation of better ventilated areas.
-hypoxia causes vasoconstriction of pulmonary vessels, vasodilation of systemic vascular
tissue.
Obstruction of vessels which limit blood flow is the most frequent cause of low blood 02
because it mismatches ventilation with blood flow leading to respiratory acidosis. (high
co2). Normal V/Q (ventilation perfusion ration) is 1, if airway obstruction then V/Q is
zero and Pc02 and P02 is similar to venous blood, if there is blood flow obstruction, v/q
reaches infinity and no gas exchange occurs but p02 and pC02 approach value of inspired
air.
Hemoglobin (13-18g/100ml)binding decreases (moves curve to the right): with increase
2,3DPG, Pc02, temp or decrease in PH.
-fetal Hb, and CO move the curve to the left, fetus HbF has a higher affitinity for
O2 so can be extracted from mom.
Carbon dioxide transport: HC03 in plasma and Hb (carbaminohemoglobin), principle
way transported through the blood using carbonic andhydrase which combines C02 with
H20. It is transported in the opposite of Cl- influx.
-Haldane effect: for any pc02, Hb carries more c02 when 02 decreases.
-Hemoglobin H (four beta chains), alpha-thalassemia (4 alpha chains), Hemoglobin C
(reduced plasticity of Hb), Hemoglobin A (NORMAL), Hemoglobin S (Sickle Cell)
-Myoglobin: much greater affinity for oxygen compared to Hb, so can pick up 02 at
lower p02.
Blood serum: blood plasma (filled with proteins) minus fibrinogen or clotting factors.
-lacks fibrin, clear, thin, and sticky.
Respiratory control centers: reticular formation of medulla oblongata and the pons
-inspiratory neurons in upper medulla and send down alpha motor fibers to
muscles of inspiration, and inhibitory inspiratory neurons
-expiratory motor neurons in lower medulla only during FORCED expiration and
work via alpha motor fibers, can also inhibit.
CENTERS of PONS
-pnuemotaxic center is the inspiratory inhibitory center located in the upper pons
and is stimulated by the medullary inspiratory neurons during respiration to inhibit the
apnuestic center during inspiration until inspiration ends and expiration finally begins.
-apneustic center for inspiratory initiation in the LOWER PONS, activates medulla,
inhibited by lung inflation receptors\
Hering-Breuer reflex (stretch-inflation reflex): inspiration causes lung inflation which
activates stretch receptors with activates VAGAL FIBERS to the TRACTUS
SOLITARUS which causes apnuestic center inhibition and causes expiration.
Juxtacapillary receptors: (j receptors) cauased my pulmonary diease and causes rapid and
shallow breathing.
Propriocenter control: gamma efferent fibers
Peripheral chemoreceptors: carotid bodies located at birfurcation of common carotid
arteries which respond to low 02 and high c02, at the level of the thyroid cartilage.
(glossopharyngeal nerve like carotid sinus)
-remember: carotid sinus and aortic arch are for baroreception.
-peripheral receptors are not as important as central receptors in responding to
changes in arterial pC02.
-increase in acidity causing chemoreceptors to increase breathing rate independent
of Co2 level.
Central chemoreceptors: in ventral surface of MEDULLA exit of 9th and 10th cranial
nerves, activate apneustic center of brain.
-sensitive to CSF ph, increase in pC02, low 02 does not stimulate central
chemoreceptor AT ALL.
Chronic lung disease is due to hypoxemia, rather than C02 levels, high 02 is
contraindicated as treatment because it removes hypoxic drive leading to severe
hypoventilation.
Inspiratory muscles: diaphragm contracts, external intercostals pull ribs up and forward
-succinylcholine has inhibit muscles, so can myasthenia gravis.
ACTIVE expiration: rectus abdominas, internal and external oblique muscles, transversus
abdominus, and internal intercostals.
At FRC (fuctional reserve capacity) airway pressure equals atmospheric.
Inspiration: inspiratory muscles, chest expands pulling on parietal pleura, this lowers
intraplueral pressure making airway pressure subatmospheric.
-transmural pressure is negative
When transmural pressure is positive, there is a FORCED expiration, it is the difference
between the alveolar pressure and intraplueral pressure.
Lung Compliance; change per volume per unit change in pressure, at high volumes
compliance is low, and low volumes, compliance is high.
-compliance is reduced by stiffness and increased pulmonary venous pressure,
atelectasis (collapse of lung), of fibrotic dieases of lung. IT IS INCREASED BY
EMPHYSEMA!, and surfactant which decreases surface tension.
-with surfactant, alveoli remain patent at the lower pressures of inflation,
stabilizes alveolo, and keeps alveoli free of H20.
-surfactant is made by TYPE II pnuemocytes, made of CHOLINE.
-hysteresis: lung volume is greater at any pressure during deflaction versus
inflation.
Histotoxic hypoxia: Occurs when the tissue cannot utilize the delivered 02 because of a
toxic agent (cyanide), everything else is normal.
Respiratory response to exercise:
Phase 1: increase in ventilation due to cerebral input
Phase 2: peripheral chemoreceptors , ph continues to fall, increase in ventilation is
proportional to 2 consumption
Phase 3: steady-state, aterial c02 tension is regulated, after exercise there is an
abrupt decrease in ventilation, stimulus for ventilation remains because of acidity of
blood but pc02 is normal and 02 remains normal or high. ATP and phosphorlycreatine is
resynthesized and lactic acid is removed.
NERVOUS SYSTEM PHYSIOLOGY:
Resting membrane potential is formed largely because the neuron is permeable to K+ and
impermeable to intracellular anions. The positive K+ ions diffuse across the membrane
leaving a impermeant negative charge behind, they stop when the magnitude of the
electrostatic force is equal and opposite to that of the concentration gradient.
The absolute refractory period is that time during which Na channels cannot reopen, in
the relative period the Na channels can open but it is harder because of the K dependent
hyperpolarization.
-Anasthetic, binds to SODIUM channel put them in the closed position, they do
Doral columns: discriminative touch go to nucleus gracilis and cuneate nucleus in the
lower medulla, these fibers cross and then ascend in the contralateral medial
lemniscus to terminate in the thalamus.
Anterolateral pathway: pain, temperature, crude touch sense, dorsal horn cross spinal
cord, terminates in thalamus via the spinothalamic tract then to the cerebral cortex.
BOTH terminates the ventral posterior lateral nucleus of the thalamus.
Sensory felt on body is found on the opposite side of the cortex.
A-gamma and C-fibers synapse in the dorsal horn.
Substance P: C-fiber afferents in central synapses
-spinal pain projections: spinothalmic tract, include reticular formation, superior
and inferior colliculi, and periaqueductal grey matter (opiate release e.g. serotonin)
-VPL of thalamus
-endorphins act in peripheral analgesia in part by preventing the release of
substance P from C-fiber afferent terminals.
Pupil:
Light entering one eye causes constriction of the contralateral pupil (consensual light
reflex), it is mediated by the Edinger-Westphal nuclei.
Pupillary constriction occurs when focusing for near vision (accommodation). It is
mediated via a different pathway from the light reflex.
-tertiary syphilis: Argyll-Robertston pupil, reflex constriction is lost but
accommodation constriction is preserved.
Focusing of eye triad: accommodation, papillary constriction, eye convergence.
Receptors: rods and cones are exited and that inhibit bipolar cell in the dark
(hyperpolarization)
Rhods: contain rhodopsin, which contiains sctotopsin, and vit A. (11-cis-retinal) for light
trapping.
Cones: visual acuity and color vision, central location.
Horizontal and amacrine (local-circuit neurons of the retina) bipolar(inhibited in the dark)
and ganglion cells (transmit to brain, synapses with bipolar cell)
Visual cortex: lateral geniculate which received input from contralateral field.
-pyramidal cells: project to other areas of the brain
-stellate cells: local integration
Ear:
Sound waves in the ear enter the eardrum (tympanic membrane) to vibrate and cause the
ossicles to produces pressure changes in the inner ear.
-tympanic reflex: tensor tympani and stapedius lock ossicles into place to
prevent damage to the inner ear to loud sounds.
-Organ of corti rests on basilar membrane, innervated by CN 8, the hairs of the
hair cells are embedded in the tectorial membrane, doformation of the hair cells occurs
when the basilar membrane generates action potentials.
-Basilar membrane: movement of stapes produces pressure waves in the
perilymph of the scala vestibuli to trigger hair cells in the organ of corti.
Basal ganglia: movement, pars compacta of substantia nigra, dopamine, its function
is INHIBITORY, so if damaged causes tremor/tonic action. The CEREBELLUM IS
EXCITATORY.
Parkinsons: tremor at rest, cogwheel joints, tonic action of alpha motor neurons,
difficulty of initiating skilled movements (akinesia)
Huntingtons chorea: decreased levels of GABA, opposite of parkinsonism,
hyperkinesias, involuntary movements, spasmodic
Lesions of subthalmic nucleus: violent flinging of contralateral arm
Basal ganglia has initiating and directing complex movements.
Cerebellum: receives fast inputs of motor activity, thus it can make quick constant
corrections to motor activities while they are in progress.
Rubrospinal: coordination of body movement
Lateral reticulospinal: facilitary influence on skeletal muscles/motor neurons.
Medial reticulospinal: inhibitory effect on motor nuerons
Lateral & Anterior corticospinal: voluntary movement, muscles, movement on opposite
side.
Speech disturbances:
Dysarthria: motor output disturbance
Brocas aphasia: lesion to inferior frontal gyrus, no comprehension deficit, speech is
nonfluent
Wernickes aphasia: lesions of posterior portion of the superior temporal gyrus, no motor
problem just cannot understand
Conduction aphasia: lesion in fibers between Wernicke and Broca, cannot convert
auditory input to verbal output.
Sleep:
During REM, EEG resembles waking state, autonomic tone increases (increased HR and
blood pressure), and skeletal muscles are paralyzed. (after 90 minutes from onset of
sleep)
-drives by pons, lateral geniculate, and visual/occolumotor cortices
Wakefulness: B-waves
Non-rapid REM: slower frequency and high-voltage activity, stage 1-4, where stage 4 HR
and blood pressure and respiration declines, BUT GI motility increases and muscle tone
is maintained.
REPRODUCTIVE PHYSIOLOGY:
The major progestin, progesterone is made in the greatest quantities in the ovary, or can
be made in adrenal cortex.
Androgens and estrogens can be made in the ovaries, testes or adrenal cortex and have
activity in both males and females.
Androgen secretion: testosterone is created via pregnelenone, (17 a hydroxylase
enzyme) 17-hydroxy pregnelenone, DHEA (zona reticularis) then gets transformed to
Androstenedione and testosterone in the tests and ovaries, and is created in the Leydig
cells of the testis and the adrenal gland.
-transport to the blood is by sex hormone binding globulin.
-activates mRNA transcription in prostate, hair follicles, and external genitalia.
Spermatogenesis: initiation by Sertoli cells, under FSH and testosterone of Leydig
cells. (paracrine effect)
Internal ducts and organs:
-Epididymis: high levels of testosterone
-vas deferens: testosterone helps muscular components and epithelial lining
-seminal vesicles: production of seminal fluid
-prostate: convert testosterone to DHT, which causes growth and secretion in
the prostate gland, can cause benign prostatic hypertrophy.
-scrotum: DHT is responsible for thinning and development of fold of the
scrotum, increase surface are to keep testes cool
-penis: enlargement of penis at puberty controlled by DHT.
DHT: development of public and axillary hair in BOTH males and FEMALES. Increases
sebaceous gland activity causing acne, deepening of voice.
Testosterone: anabolic steroid to build mucles, increase protein synthesis in muscles and
overall muscle mass, increase growth at end plates of long bones and stimulate the
closing of the epiphyseal plates, so androgens also limit growth.
LH: stimulate leydig cell to synthesize and secrete testosterone
FSH: stimulate sertoli cells to synthesize and release ABP and inhibin.
-inhibin feeds back to the pituitary gland to block synthesis and secretion of
FSH. (in both females and males)
-testosterone synergizes with FSH to initiate and maintain spermatogenesis.
Sperm transport: testis to epididymis (not motile), stored in epididymis where they
become motile by forward motility factor in the tail, but they ARE NOT FERTILE.
Vas deferens push the sperm to the urethra, fluid from prostate and seminal vesicles is
secreted (which contains fructose and prostaglandins).
Female reproduction:
Cells in theca interna have receptors for LH, stimulates conversion of cholesterol to
pregnelenone, transported to androgens from the thecal cells to the granulosa cells where
they become estrogen, and are promoted by the FSH binding to the granulosa cells,
which also creates more LH receptors on the granulosa cells.
Corpus luteum: derived from both theca interna cells and granulosa cells. Theca
interna cells create more aromatase.
Progesterone binds to corticosteroid-binding globulin, wherease estradiol and DHT and
androgens binds SHBG.
-prepares uterus for preganacy, further proliferation of the endometrium
Estrogen acts by increasing oxytocin receptors in the fallopian tubes, and stimulate
contraction of the fallopian tubes. Estrogen promote endometrial growth and increase
both the length and number of the endometrial glands.
Mannitol acts like NaCL in the blood for patients with cerebral edema so it drives water
from the brain to the blood vessels.
Capillary blood pressure/hydrostatic pressure (Pc) is more effected by increases in
venous pressure than arterial pressure, because arteries can regulate themselves. Thats
why, hypertension but without heart failure do not commonly exhibit edema.
Glomerulonephritis: causes primary salt and water retention as a result of damage to the
kidney, which causes a higher EDV, which causes increase in cardiac ouput.
-CHF and Glomerulonephritis increase hydrostatic pressure.(Pc)
-atrial natriuretic factor can be used to treat problem to decrease reabsorption and
promote diueresis. USES cyclic GMP as a second messenger.
Liver disease causes a reduction in plasma volume causing accumulation of fluid in the
perotineal cavity (ascities) or edema, causing the kidney to increase reabsorption
furthering the edema.
-hypoalbuminemia also causes generalized edema (occurs from low plasma
oncotic pressure, whereas low interstial oncotic pressure causes localized edema).
-albumin: decreased in malnutrition, liver failure, and PREGNANCY. Transports
thyroxin, fatty acids, bilirubin, bile acids, steroid hormones, ions. IT IS NOT
GLYCOSYLATED.
Nephrotic syndrome: Plasma protein falls from mass excretion of protein, lowering
plasma oncotic pressure causing GENERALIZED edema. The reduced oncotic pressure
causes fluid to leak into the interstitium, lowering plasma volume, resulting in secondary
salt and water reabsorption by the kidney. hypoalbunimia and secondary hypovolemia.
Nephritic syndrome: aka glomerulonephritis. Associated with high plasma volume,
whereas nephrotic syndrome is associated with hypoalbunimia and secondary
hypovolemia.
Burns increase capillary permeability which increase leakage of plasma protein into
interstitium cuasing increase in interstitial oncontic pressure, causing edema. Also
Histamine release causes vasodilation with increases capillary hydrostatic pressure.
Wuchereria bancrofti is a worm that causes a block in lymph channels causing local
edema. Malignancies also cause local edema of the lymph nodes because of blockage of
lymph flow.
Nephron: glomerulus, bowmans capsule (single layer of specialized epithelial cells),
proximal tubule, loop of henle, distal tubule, collecting duct.
Cortical nephrons: outer cortex, have short loops of Henle, hairpin turn in distal area
Juxtamedullary nephrons: deep into cortex, smaller percentage, have long loops of Henle
deep in medullary zone and papillary portions of the kidney.
Podocytes: specialized epithelial cells that lay down and maintain basement membrane
and scavenge proteins that slip through the filtration barrier, they contact glomerular
capillaries via pedicle, which are interdigitating foot processes that rest on the outer layer
of the basement membrane. Spaces between pedicle alow filtration of protein allowing
water and solutes to pass.
-angiotensin II also cause greater constriction of the efferent arteriole than of the
afferent arteriole. Can be released by B receptors, reduction of perfusion pressure in
kidney, or reduction of Na delivery to the macula densa.
-Para-aminohippuric (PAH) acid is a substance used to measure renal
plasma flow.
-decrease in plasma colloid osmotic pressure (decrease in plasma proteins),
causes an INCREASE in GFR.
Hematologic/Lymphoreticular Physiology
Platelets derived from megakaryocytes in the bone marrow.
Adhesion: lysine and hydroxylysine attract platelets, adhesion requires von Willebrand
factor, which binds platelet factor 8 and binds to platelet membrane glycoprotein GpIb.
F is released from platelets and promotes aggregation., TxA2 promotes platelet
aggregation, PGI2 made by endothelial cells inhibits aggregation.
Thromboplastin results in the formation of a clot
PF3 is involved in plasma coagulation.
Prostacyclin: vasodilator, inhibits platelet agregration (TxA2 is opposite)
Intrinsic pathway in which coagulation begins in the blood, whereas the extrinsic
pathwhay begins with trauma to tissues outside the blood vessels.
Extrinsic Pathway: initiated with tissue thromboplastin (tissue factor III) and tissue
phospholipids. Tissue thromboplastin along with calcium and forms a complex with a
factor VIIa which acts on factor X with factor 5 form complex prothrombin activator.
-assesed by measuring prothombin time (PT)
-3,7,10
Instrinsic Pathway: PF3 and calcium activate factor XII acts on factor XI which acts on
factor IX with factor VIII with phospholipids activate factor X which activates factor
V and platelet phospholipids active prothombin activator. (same as extrinsic)
-assessed by measuring PTT partial thromboplastin time
-12,11,9,8,10
Prothrombin made by extrinsic or instrinsic pathway needs vitamin K, creates thrombin
by breaking glycine and arginine bonds. (Warfarin is a analog of vit. K)
Factors 2,7,9,10, protein C, and protein S are all Vitamin K dependent.
Factor 13 (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.
-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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1 Function
2 Reactions
3 Regulation
o
3.1 NAcGlu
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
OTC
mitochondrial
ASS
cytosolic
argininosuccinate
Arg + fumarate
ASL
cytosolic
Arg + H2O
ornithine + urea
ARG1
cytosolic
Summary reaction:
[edit]
Regulation
mitochondrial
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)