BIOCHEMISTRY:

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.

Glycerol becomes Glycerol 3 Phosphate

Odd numbered fatty acids: produce propionly-CA which can be converted to succinyl
CoA and acetyl-CoA which IS NOT a precursor of glucose.
GLUCAGON cause increase of protein degradation because AA can be converted to
glucose, and increases lipolysis and oxidation which supplies energy for gluconeogenesis.
Skeletal muscle degrades glycogen rapidy. In white muscle/fast muscle fibers,
glycogen is broken down, whereas in red muscle, pyruvate is completely oxidized by
the TCA.
Glycogenolysis:
Glycogen Phosphorylase: cleaves a1,4 linkages, activated by glucagon or epinephrine.
-active form phosphorylase a is phosphorylated.
-cAMP phosphorylates many molecules of phosphorylase kinase which activates
glycogen phosphorylase. cAMP also phosphorylates glycogen synthase (makes a14
linkages) which inactivates it to the D form. (SO PHOSPHORYLATION INCREASES
GLUCONEOGENESIS, no phosphatases are involved).
Glycogen synthesis: creates glucose 6P which is converted to glucose 1P by
phosphoglucomutase and activated by UDP-glucose to add to glycogen primer.

Hexose Monophosphate Shunt: DOES NOT CONSUME OR PRODUCE ATP

Produces NADPH for:
synthesis of cholesterol
fatty acids
steroids
Needed for RBCs to maintain gluthathione to neutralize superoxide and h202.
Help neutrophils to make superoxide for killing bacteria (deficiency causes chronic
granulomatous disease)
Produces ribose-5-phosphate which release c02 and NADPH and can be reconverted to
fructose 6-p. For every six moles of glucose 6 p, 6 c02 are released and 5 fructose 6 p can
be produced.
The whole cycle is inhibited by NADPH and palmitoyl-CoA.
Fructose metabolism: Fructose is converted to f1p then uses aldolase B to convert it to
DAH and G3P.
Galactose metabolism: galactose is converted to galactose 1 P which is transferred to
glucose 1p by uridyl transferase.
LIPID METABOLISM:
Saturated: no double bonds
Unsaturated fatty acids: Contain double bonds in CIS configuration
Monosaturated fatty acids: oleic acid (18C), palmitoleic acid, erucic acid.
Polysaturated fatty acids: linoleic acid & linolenic acid (essential fatty acids), arachidonic
acid

-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.

Produce ketones (from spontaneous decarboxylation) when inadequate carbohydrate is

avalialble to the extrahepatic tissues. Synthesis by HMG-CoA synthase, not reductase.
HMG-CoA reductase is key in producing cholesterol. (inhibited by levostatin).
Lipase: EPI, NORE, and glucagon increase cAMP which activates this enzyme, causing
TAG hydrolysis. Glycerol is sent to liver for gluconeogenesis and fatty acids released
bind to albumin.
Lipoprotein Lipase: found in endothelial cells of adipose and muscle tissue. Hydrolyzes
VLDL and chylomicrons into muscle and adipose tissue.
Cholesterol Synthesis: Occurs in liver and other tissues in the cytosol or ER
First step: three acetyl-CoA to produce HMG-CoA then it is reduced to mevalonic acid.
Uses 2 NADPH.
KEY ENZYME: HMG-CoA reductase in cytosol, the one in the mitochondria is used for
ketone synthesis!
-rate limiting enzyme, promoted by insulin and thyroxine, inhibited by glucagon.
Then isoprene units IPP and DPP form squalene (30 carbon)
Fatty acids incorporated into cholesterol: OLEIC ACID
Cholesterol esters: Use LCAT (leaving cholesterol via HDL) and ACAT (Accumulation
of cholesterol in cells).
Steroid Hormone production: Comes from cholesterol
Cleavage of cholesterol creates pregnenolone (C21) which is converted to progesterone,
which are the precursors to ALL steroid hormones. Desmolase is the rate limiting
enzyme.
-desmolase is promoted by angiotensin/ACTH (mineralcorticoid), LH (androgen
and estrogen synthesis)
5-a-reductase: reduces double bond in testosterone to form DHT which is a major
androgen.
Aromatase: converts androgens to estrogens.
Estrogen: unlike other steroid hormones, has aromatic A-ring.
Sphingolipid/glycolipid synthesis: palmitoyl-CoA, serine, fatty-acyl CoA. Use UDPsugars and CDP-choline, PAPS, and CMP-NANA (very similar to phospholipid)
Sphingolipid: only one with PHOSPHATE
Cerebrosides/globosides: contain glucose of galactose
Gangliosides: contains nueramic acid/sialic acid
Diseases are all AUTOSOMAL RECESSIVE:
Gaucher: glucocerebrosides
Fabrys: a-galactosidease, increase ceramide trihexoside
Tay-Sachs: increase gangliosides, hexosaminidase A deficiency
Niemann-Pick: sphingomyelin, sphingomyelinase deficiency
Farber: increase ceramide

Hurler syndrome: increase heparin sulfate, dermatan sulfate, deficiency of iduronidase.

Luekotrienes > SRS-A (smooth muscle constrictor in inflammation and chemotaxis)
AMINO ACIDS:
Non-essential are made in the LIVER
Arginine and Histidine are essential only in children.
Essential In adults: PVT TIM HALL (a=arginine??, t- tryptophan, threonine)
Digestion: enteropeptidase activates trypsinogen which activates other proteases.
Diseases: hartnup disease (causes decrease in tryptophan/niacin/pellagra)
Cystinuria: causes kidney stones by excreting amino acids.
Catabolism: pyridoxal phosphate, transamination, oxidative deamination of glutamate.
Most use a-ketoglutarate as an acceptor creating glutamate which can become ammonia
or transferred to oxoloacetate.
Glutamate fate: is unique in that it is the only amino acid that undergoes rapid
oxidative deamination (release ammonia).
Convert to a-ketoglutarate and NADH by using dehydrogenase
transamination with oxoloacetate to make a-ketoglutarate and aspartate
Urea formation: Arginase directly catalyzes urea formation.
apartate and ammonia/bicarbonate become fumurate and urea.
first two enzymes in mitochondra, the last steps in cytosol
Steps: Nh4 + Hc03 + ATP = Carbomoyl phosphate, add ornithine to get citrulline (COC)
Now in cytosol: citrullin combine swith aspartate to make arginosuccinate which makes
fumarate and arginine, and arginine becomes urea and ornithine (which is recycled).
controlled by CPS-I and NAG (N-acetylglumate) activated by increase in proteins and
glutamate accumulation.
Alanine: converted to pyruvate and glutamate in the liver which becomes urea.
Glutamine: glutamine becomes glutamate when it loses ammonia, or the reverse can
occur.
Ketogenic amino acids: Luecine and Lysine can become acetyl-CoA or ketone bodies
Ketogenic and glucogenic: isoluecine, phenylalanine, tyrosine, tryptophan. Which can
also become acetoacyl-CoA which can become acetyl-CoA.
Asparagine and Aspartate can become oxaloacetate
Tyrosine and Phenylalanine and Arginosuccinate can become fumurate
Valine and propionly-CoA (odd chain FA and isoluecine and methionine and threonine)
can become succinly-CoA
Alanine, serine, cystiene, and glycine can become pyruvate.
Proline, Arginine, Histidine, Glutamine become glutamate which can become aketoglutamate.
Non-essential: Phenalalanine becomes tryptophan with hydroxylase
Cysteine is made from serine and methionine.
Glutamate GABA
Histamine Histidine
Serotonin tryptophan
Tyrosine: Catecholamines, melanin, thyroxine.

Arginine: becomes nitric oxide and ornithine

AST (aspartate transaminase), ALT (alanine transaminase): not involved in oxidative
deamination reactions which liberate ammonia.
Remember: Fat can never be converted to carbohydrate or protein
Kidney cortex only uses fatty acids for energy
Kidney medulla only uses glucose
RBCs can only use glucose for energy source
Growth Hormone (stomatotropin): Causes increase in gluconeogenesis and increase in
liver glycogen, CAUSES SHIFT from using carbohydrates to USING FAT FOR
ENERGY. It is increased by sleep, starvations, exercise, hypoglycemia, it is
decreased by obesity, somatomedins, somatostatin, and PREGNANCY.
Molecular Biology:
B-DNA: most common, right handed, antiparallel, helical, 10.5 bases per turn
Z-DNA: left handed, GC rich, rare
A DNA: bases are not perpendicular to axis, but 20 degree shifted
DNA polymerase III is the major replicated enzyme in E. coli.
-another enzyme unique to E. Coli is DNA Gyrase (topoisomerase)
-E. Coli contains a SINGLE ori start replication site.
-E. Coli also has 2 recognition sites for RNA Polymerase
Recombination occurs during metaphase, causes allelic changes not the gene sequence.
Negative supercoils: found in prokaryotes and linear eukaryotic DNA
Pyrimidines are synthesized while attached to ribose 5 phosphate
Defect in purine and pyramidine metabolism can lead to gout.
-Other diseases:
Lesch-Nyhan Syndrome gout and mentally retarded
SCID: deficiency of adenosine deaminase, results in defectinve T & B lymphocytes,
increase in dATP which inhibits DNA synthesis (ribonucleoside reductase)
Both prokaryotic and eukaryotic DNA synthesis is bidirectional, begins at ori sequence
Lagging strand is discontinous Okazaki fragments, while leading strand is continous
DNA Repair diseases:
Xeroderma pigmentosa: cant fix UV mutations, defect in excision repair
Ataxia telangiectasia: dilated blood vessels, lymphomas, defect in endonuclease base
excision repair
Transcription:
Pribnow box: AT RICH, -10, promoter, initial unwinding.
Hexamer at -35 site, bind to promoter of RNA polymerase
TATA box: initiation site in eukaryotes.

Termination: Rho-independent with a hairpin loop, or Rho factor that terminates

transcription of RNA Polymerase
RNA synthesis is NOT proofread, usually no primer is required.
In prokaryotes, translation and transcription are coupled, to translation begins before
transcription ends.
In eukaryotes, trxn and translation are not coupled to extensive modification occurs
before translation. (splicing, capping, polyadenylation)
Translation
Shine-Dalgarno sequence AUG
rRNA: most common RNA
prokaryotes: 23s, 16s, 5s rRNA (30S, 50S = 70S)
Eukaryotes: 28S, 18S, 5.8S, 5S (40S, 60S = 80S)
tRNA: Amino acid attachment site has CCA
E-P-A: the A site tRNA is bound to carboxyl group of amino acid bound to P site tRNA.
Translocation involved peptide formation and GTP hydrolysis.
Lac operon: activated by absent repressor (bound to inducer) and presence of activator
(low amount of glucose which increases cAMP production of promoter)

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.

Achalasia: inability for LES to relax

Esophageal reflux: occurs because of incompetent LES, allow gastric to go up esophagus.
Stomach: outer longitudinal layer and inner circular muscle and UNIQUE third inner
oblique layer.
-pylorus is continous with circular muscle layer, and contraction is modulated by opiods
like enkephalins.
-afferent and efferent impulse by vagus, relaxation by VIP and N20.
-contraction occurs from outer long. And inner circular muscle
-emptying is controlled by CCK, which inhibits gastric emptying
Duodenum: Brunners glands and goblet cells in the mucosa
-G cells produce Gastrin in the atrum(near pyloric sphincter) of stomach and duodenum
-causes stimulation of HCL secretion by parietal cells (also secrete intrinsic
factor)
-stimulate histamine release from enterchromaffrin cells (also release serotonin)
-stiumulate pepsinogen secretion from chief cells
-contraction of circular muscle of stomach.
Antrum: Mucous cells (secrete mucus and pepsinogen) & G cells (Gastrin)
Body: Chief Cells and Parietal Cells (body)
Fructose is by FACILITATED diffusion, GLUCOSE by active transport (Na)
CCK: I cells, gallbladder contraction, pancreatic enzyme secretion, inhibit gastric
emptying.
Secretin: S cells, in duodenum, stimulation of bile and inhibit H+ of parietal cells,
inhibits stomach motility, stimulates pancreas to release bicarbonate ions.
GIP: K cells, stimulate pancreatic insulin
VIP: stimulate water and salt secretion, relaxation of muscle and LES and relaxation of
stomach.
VIPoma: watery diarrhea
Somatostain: D cells, inhibits gastrin, CCK, and other hormones.
Substance P: pain impulses, myenteric plexus of vagus
Plasma cells: IgA
Vitamin B12 is absorbed in the ileum.
Oligosaccharides are hydrolyzed in the midjujenum and ileum by the brush border
-lactose intolerance: increase water secretion causing diarrhea
Water and electrolytes (Ca, iron and folate) are reabsorbed in the jujenum and duodenum
Cl- is exchange with HC03 in the ileum and colon
Large intestine: larger in diameter and shorter in length than the small intestine
-teniae coli: longitudinal bands of muscle, pouching causes HAUSTRA
-NO VILLI
-abundant lymph follicles in the cecum and appendix
-main function: reabsorption of fluid and electrolytes and temporary storage of feces.

-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)

-become the Purkinje fibers which PENETRATE ventricular myocardium

(papillary muscles), purkinje fibers undergo RAPID CONDUCTION.
Effective refractory period: no AP can be elicited, whereas in relative refractory period
where propagated AP can be elicited but only with a strong depolarizing stimulus.
Myocardial contraction: L type Calcium channels, T-tubules from sarcolemma
invagination, entry causes release of stronger number of calcium ions (ca induced ca).
Calcium binds troponin, allowing binding to tropomyosin.
CARDIAC MUSCLE: CHANGES IN CONTRACTION DUE TO CHANGES IN
CONTRACTILITY OF FIBERS, NOT NUMBER OF FIBERS ACTIVATED LIKE IN
SKELETAL MUSCLE.
Left ventricular pressure at the end of systole represents: end-diastolic pressue
FOURTH heart sound: occurs during atrial systole, but audible only in pathological
conditions where there is forceful systole. (atrial gallop)
Ventricular systole: (QRS complex)
Left ventricular pressure increases with close the mitral valve and aortic valve is closed,
while the volume remains the same (isovolumetric contraction).
FIRST HEART SOUND: coincides with AV valve closure (mitral and tricuspid),
loudest and longest sound continuing into early ejection.
-can be loud in mitral stenosis, if it is absent it represents mitral calficication.
Ventricular ejection when left ventricular pressure rises above aortic pressue opening the
aortic valve.
AORTIC VALVE OPENS AFTER THE PULMONIC VALVE OPENS.
Ventricular diastole:
Isovolumetric relaxation: Both the mitral and aortic valves are closed and the ventricles
relax, aortic valve closure is the beginning of isovolumetric relaxation.
SECOND HEART SOUND: Coincides with semilunar valve closer of aortic
valve and the pulmonary valve closure.
-there is a splitting of the sound between aortic and pulmonary closure, due to the
aortic valve closing before the pulmonary valve.
Ventricular filling occurs when the ventricular pressure falls below the left atrial pressure
opening the mitral valve, which defines the beginning of ventricular filling.
THIRD HEART SOUND coincides with rapid ventricular filling/ventricular
gallop.
(heart sounds are best heard over the left ventricular apex with the patient in left lateral
decubitis position)
Murmurs: originating on the right side of the heart generally increase with inspiration and
those from the left side decrease with inspiration because inspiration increases venous
return.
-caused by stenosis or atrial septal defect. (systolic ejection murmer)
-usually occur between S1 and S2 sounds (pansystolic murmur)
-mitral, tricuspid, ventricular defect/regurgitation
-After S2: Diastolic murmur aortic, pulmonic, or mitral stenosis/regurgitation

Cardiac Output: SV (blood pumped by ventricle per beat) X HR

SV = EDV-ESV (end diastolic end systolic)
SV increases by increasing preload, and decreasing afterload
Preload: force of contraction during the initial muscle stretch, EDV (Starlings law)
Afterload: Aortic pressure, force of contraction, aterial resistance to the heart
Cardiac muscle: varying degrees in which ALL muscle fiber is activated.
Positive iontotropes: increase Ca influx, digitalis (ATPase blocker)
-decrease afterload, and increase heart rate
Negative ionotropes: verapamil (Ca blocker), acidosis, B antagonist
acetylcholine - ONLY EFFECTS ATRIA NOT VENTRICLES
-increases afterload
Blood flow:
Laminar: blood flow in concentric layers within the vessel
-Bernoullis principle: as diameter decreases, velocity flow increase.
Turbulent: blood flows chaotically, in proximal aorta and pulmonary artery
Mean arterial pressue: 1/3 systolic + 2/3 diastolic pressure
Venous compliance: under control of sympathetic nervous system (alpha receptors) and
greatly affected by gravity.
-abdominothoracic pump of inspiration: inspiration causes intrathoracic pressure
to decrease and abdominal pressure to increase causing blood flow to increase to thoracic
vena cava from abdominal vena cava.
-venoconstriction: cause by B1 receptors of sympathetics
Arterial blood flow: alpha causes constriction, b2 causes vasodilation
-arterioles can become metarterioles which are divided by the capillary sphincter.
Transcapillary exchange: (capillary hydrostatic pressure interstitial h.p) ( capillary
oncotic pressure interstial oncotic pressure)
During exercise: decrease in peripheral resistance (vasodilation) but increase in cardiac
output is greater, so pressure in arteries increases. Stress causes increase in peripheral
resistance (decrease in arterial compliance).
-largest drop in blood pressure occurs In transition from arteries to
arterioles.
Lymphatics: left side of head, arm, chest into thoracic duct which empties at junction
between internal jugular and subclavian vein.
-same on right side, but right lymph duct into right i.j. vein and subclavian
Coronary artery pressure: During systole, coronary artery pressure is less that aortic
pressure beause of rapid flow (bernoullis principle high compressive forces during
systole on artery), during diastole, aortic valve is competent and is transmitted to
coronary arteries. (diastole = coronary blood flow)
Coronary sinus pressure = right atrial pressure
Tachycardia causes decrease in duration of dystole more than systole effecting coronary
blood flow, compromising blood flow to the heart.

-during sympathetic stimulation, tachycardic, but release Adenosine to cause

coronary vasodilation to make up for increase in heart pressure.
Parasympathetic system: release Ach on ATRIAL muscle via M2 receptors.
Baroreceptors: carotid sinus (bifurcation) and aortic arch (arterial) and heart/lungs.
Function is to REDUCE acute symptoms, increasing during systole and decreasing
during diastyole. A decrease in arterial pressure causing a decreasing in firing which
causes vasoconstriction and increased heart rate.
-cartoid sinus: CN 9
-aortic arch: CN 10
Carotid receptors located between right atrium and the vena cava and of the left atrium
and pulmonary veins.
-activation during filling and contraction causes INCREASE in heart rate
(Bainbridge reflex), secreation of ANF (atrial natriuetic factor, which increase sodium
excretion), and decrease of ADH.
ECG:
p-wave: depolarization of atria
PR: depolarization of AV node and bundle of his/purkinje (time for SA node to reach AV
Node), ISOELECTRIC
QRS: depolarization of ventricles
ST: ISOELECTRIC, elevation of depression means pathology/MI
T: repolarization of ventricles, elevation or inversion shows pathology, hyperkalimia.
QT interval prolonged in CHF and hypocalcemia, shortened by digitalis and
hypercalcemia.
RR interval: HR = 60/RR
ARYTHMIAS:
First degree AV Block: prolonged PR interval
Second degree AV block: failure of conduction of impulse from atria to ventricles
Acquired third degree AV block: requires pacemaker
Bundle Branch Block: If unilaterial, cause splitting of the second heart sound
Escape beat: if SA Node fails to depolarize such pacemaker cells
Supraventricular arrhythmias: normal QRS complexes
-abnormal P wave, premature atrial contraction
-wandering atrial pacemaker
Paroxysmal supraventricular tachycardia: Re-entry mechanism originating from AV node
or atria.
Atrial flutter: flutter waves, SAWTOOH appearance, block is present
Atrial fibrillation: normal QRS complexes but an abnormal intervals.
MAT: slow atrial rate
Ventricular arrythmias: abnormal, wide, and bizarre QRS complexes.
-premature ventricular contraction: ectopic beat
-ventricular tachycardia: re-entry mechanism, decrease in CO, and decrease time
of ventricular filling.

-Ventricular fibrillation: multiple ectopic ventricular foci, need implanted

defribillator.
-Torsades de Pointes is a from of ventricular tachycardia in which QRS complex
change cyclically in patients with prolonged QT interval.
Congestive Heart Failure: inability of heart to deliver a sufficient cardiac output to meet
the metabolic demands of peripheral tissues, despiste elevated cardiac filling pressures.
-increased afterload, preload, valvular disease, tachy/brachycardiam, impaired
myocardial function
-constant sympathetic elevation, tachycardia, rennin levels are elevated, ADH is
elevated, development of peripheral and pulmonary edema.
Symptons: dyspnea on exertion, orthopnea, nocturnal dyspnea, S3 gallop because of
excess venous return to right atrium. Cardiac hypertrophy and cardiomegaly
-PULMONARY RALES/EDEMA, in portions of the lungs
-JUGULAR VENOUS DISTENSION 2cm above the sternal angle
-postive Kussmauls sign: jugular venous pressure increases with
inspiration
-Hepatojugular reflex, venous pressure increase while put pressure over abdomen,
HEPATOMEGALY and SPLENOMEGALY.
-EDEMA: pitting, (of the entire body is anasarca) & CYANOSIS.
-ASCITES: right-sided heart failure or biventricular failure
Cardiovascular response:
Isotonic: rhythmic contractions of flexor and extensor (running), increase 02
consumption, systolic increases BUT NOT DIASTOLIC.
Isometric or static exercise: weight lifting, fueled by lactate production, no movement,
blood pressure and o2 consumption minimally increased.
Exercise causes muscle blood flow to increase 15x, causing vasodilation, increase heart
rate, and stroke volume.
Veins have a greater compliance compared to arteries, therefore can accommodate larger
changes in volume.
ENDOCRINE PHYSIOLOGY:
Anterior pituitary: pars distalis, pars tuberalis, pars intermedia (come from stomatodeum
Rathkes pouch).
Post. Pituitary: pars nervosa, infundibulum (comes from diencephelon)
Steriods: cortisol, aldosterone, estrogen, progesterone, testosterone
Proteins: glucagons, GH, Prolactin, Calcitonin, ACTH, insulin
Glycoproteins: FSH, LH, TSH, hcG
Peptides: ADH, oxytocin, atrial natruinetic hormone, TRH, GnRH
Amino Acid derivative: thyroxine, tyrosine (NORE, EPI, melatonin)
Pituitary gland lies beneath the brain, connected to it by the infundibulum.
Anterior pituitary (adenohypophysis): derived from somatic/oral ectoderm (the roof of
stomodeum), devoid of innervation. Connected by the hypothalamic-hypophysial portal
blood system and it originates from the median eminence, filled with releasing factors
and hormones.

-TRH stimulates release of TSH and prolactin

-Somatostatin inhibits both TSH and GSH and prolactin, while dopamine inhibits
prolactin.
-hormones contain disulfide-bridges.
-Growth Hormone: increase protein synthesis (GH increases when excess AA)
decrease insulin sensitivity, increased lipolysis, secreted as pulses throughout the day.
Inhibited by somatostatins and stomatomedins, obesity, hyperglycemia, and pregnancy,
which cause negative feedback inhibition of GSH and positive feedback to somatostatins.
RELEASED IN PULSATILE FASHION.
-MSH is secreted from chromophobe cells of pars intermedia, while ACTH is
secreted from pars distalis, but ACTH has the ability to stimulate MSH,
Prolactin and Growth Hormone is produced by acidophils of pars distalis (anterior
pit.)
Posterior pituitary (nuerohypophysis): derived from nueral ectoderm, supplied by pars
nervosa. The hormones are made in the supraoptic nucleus and paraventricular nuclei.
-Osmoreceptors in hypothalamus sense changes to release ADH in post. Pit.
-ADH secretion dependent on osmoreceptors and baroreceptors (l. atrium, etc)
which inhibit ADH. Ethanol and caffeine decrease ADH release, while nicotine
increases its release.
Adrenal Gland: all peptides are derived from pro-opiomelanocortin. Cholesterol is the
precursor to the steroid hormones and converted to pregnenolone. Retinoic acid is the
only steroid hormone not derived from cholesterol. Vitamin D also has a different
structure but is derived from cholesterol.
-21 B-hydroxylase deficiency means cant create aldosterone or cortisol from
progesterone.
Zones of adrenal cortex:
Outer zona glomerulosa: aldosterone
Zona fasciculata: glucocorticouds/cortisol (main product of adrenal cortex)
Innder zona reticularis: androgens/DHEA
-cortisol has anti-inflammatory effects: block phospholipase A2 inhibiting luekotrienes,
inhibits histamine release, and production of il-2 needed for proliferation of tlymphocytes, allows glucagon and EPI to work more effectively.
-cortisol drug causes secondary addisons disease and adrenal insufficiency once taken
off medication for up to 6-9 months.
-aldosterone: promoted by rennin (JG cells), increase water absorption in COLON and
kidney, and increases K+ and H+ secretion in the kidney. (**increased K+ in plasma
causes aldosterone synthesis**), addisons disease causes hyposecretion of aldosterone.
Diseases: REMEMBER ACTH DOES NOT CONTROL ALDOSTERONE OR
ADRENAL MEDULLA.
Addisons disease/adrenal insufficiency: hypotension, hypoglycemia, hyperkalemia.
-primary: ACTH levels are elevated, severe pigmentation
-secondary: ACTH is inhibited, due to drug therapy of cortisol.
Cushings syndrome: Adrenocortical excess: obesity, facial plethora, hirsutism, menstral

disorders, hypertension, moonface, muscle wasting, purple abdominal straie, truncal

obesity.
-due to adenoma or carcinoma or chronic cortisol therapy
Hyperaldosterism: hypokalemia, metabolic alkalosis, hypertension, can be offset by ANP
production from atrial baroreceptor.
-primary: Conns syndrome, adrenal carcinomas
-secondary: increases rennin levels from kidney problem.
ADRENAL MEDULLA: NUERAL CREST DERIVATIVE
-epinephrine is derived from nore plus a methyl group.
-broken down by COMT and MAO
-main source of catecholamines isnt adrenal medulla, can live without it.
Pheochromocytoma, ganglionueroma, nueroblastoma: adrenal medulla tumors with
homovanillic and vannilylmandelic acid in urine, hypertension, hyperglycemia.
Epinephrine: glycogenolysis, gluconeogenesis. Which tend to raise blood glucose,
stimulates lipolysis in adipose tissue, increase HR, dilate briochioles in lungs, activates
muscle glycogen phosphorylase.
NORE: contrict blood vessels, lipolysis, increases heart rate.
THYROID GLAND: synthesizes T3 and T4
-thyroglobulin secreted from thyroid follicular cell and secreted into colloid space
-released via exocytosis and iodination occurs at the follicular cell surface.
-t4: thyroxine, t3:triiodothyronine
-goiter caused by low iodine uptake, pituitary enlargement can also occur, so t4 is
administered for negative feedback.
-formation of t4 includes coupling 2 DIT molecules, whereas t3 is couple of 1 MIT and
one DIT, these are catalyzed by thyroid peroxidase.
-reuptake of iodinated TG in follicular lumen by endocytosis
-both t3 and t4 are bound to plasma proteins (TBG), t4 (7 days) has a much longer half
life than t3 (one day)
-t3 and t4 enter cell nucleus and increase transcription for protein synthesis. T3 binds
with 10x higher efficiency, so it has stronger effect, but t4 (larger amount almost 20x) is
used for negative feedback and can be deiodinated to t3.
-thyroid hormone used for metabolic rate, appetite, maturation/puberty, skin, immune
system and healing.
-Goiter can occur with hyper or hypothyroidism, usually from iodine insufficiency.
-iodine insufficiency increases thyroglobulin, decreases thyroxine, TSH.
-Graves disease: autoimmune stimulate TSH receptors causing hypertrophy and
hyperthyroidism. EXOPHTHALMOS, weight loss, increased apetite, tremor,
tachycardia.
-primary: high t3/t4, low tsh
-secondary: high t3/t4/tsh
Hypothyrodism: weight gain, lethargy, coarse skin and hair, cold sensitivity.
Autoimmune thyroiditis: destruction of thyroid gland.
Parathyroid Hormone:
PTH secreted by chief cells of parathyroid gland, caused by tumors.
-increase Ca, stimulate (1alpha hydroxylase) synthesis of 1,25D3 in the kidney from

25D3 of liver, OVERALL decrease plasma phosphate by increase excretion in kidney,

increase Ca and phosphate absorption of intestine, increase ca absorption in kidney.
-Vitamin D: made from UV actiation of 7-dehydrocholesterol, liver transports it
to 25D3, PTH makes it to active 125D3 which acts on the intestine.
-rickets/osteomalacia: vitamin D deficiency, decreased osteoclast count, needed
for new bone formation and remodeling.
CALCITONIN: plasma calcium AND phosphate decrease!!!
-calcium is usually excreted in the feces (think intestine). Not urine.
Pancreatic hormones:
Alpha: glucagon, beta- insulin, gamma somatostatin, pancreatic polypeptide
Insulin created from pro-insulin and cleavage at N-terminal, stimulated by amino acids,
GIP, GH, cortisol, acetylcholine (parasymp)
Inhibited by: epinephrine, somatostatin, NOT GLUCAGON.
Glut 2: liver, Glut 4: skeletal muscle and adipose tissue
Insulin inhibits lipase by activating phosphorylase, but not lipoprotein lipase which is
needed for fatty acid uptake into tissues.
-Stimulates amino acid/protein synthesis (so does GH), and inhibits protein
degradation
-also causes hypokalemia/increase uptake of K+ into cells. (insulin is good
treatment for hyperkalemia.)
Glucagon: stimulated by Ach, EPI, NORE, Amino Acids
-Inhibited by: insulin, fatty acids, ketones, somatostatin
-increases amino acids conversion to glucose leading to INCREASED
AMMONIA.

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

NOT effect potassium, chloride, or calcium conductances. Only sodium.

Ia: muscle spindle afferents, motor nerves
Ib: Golgi Tendon organs
II: muscle spindle/nuclear chain, touch pressure hairs and vibration
IIIA-gamma: muscle spindle efferents (intrafusal)
C fibers: pain, temperature, sympathetic, postganglionic (ONLY FIBER WITH NO
MYELIN)
Spatial summation: simultaneous inputs from different presynaptics neurons
Temporal summation: additive effect on the postsynaptic neuronal memberane is caused
by repeated rapid firing of a presynaptic neuron.
Long-term potentiation: basis for learning and memory
Serotonin is released from raphe nuclei of the brainstem and from the hypothalamus.
Glutamate: excitatory
Glycine: inhibitor of spinal cord, open chloride channels
GABA: inhibitor of basal ganglia, purkinje, spinal cord, and cortical relays.
Eaton-Lambert syndrome: similar to myasthenia gravis, but patients GET STRONGER
rather than weaker, so muscles improve with use.
Clostridium Botulism toxin: causes blockage in the release of the neurotransmitter
resulting in quick paralysis of skeletal muscle and death by respiratory failure.
Black spider venom: causes complete release and depletion of AcH, muscle spasms.
Smooth muscle: synaptic cleft is much smaller, terminal are dark for norepinephrine, and
there are NO transverse tubules in smooth muscle.
AUTONOMIC NERVOUS SYSTEM:
Coordinates and modulated the viscera.
Preganglionic is myelinated, the postganglionic is not myelinated, it is 100x slower than
skeletal motor conduction.
Sympathetic nervous system: originates in the intermediolateral cell column in spinal
segments t1 to l2. activates body in synchronous coordinated fashion
-Alpha and Beta receptors: (a1,b1 = excitiation, a2,b2=relaxation)
-preganglionics leave in WHITE RAMUS (myelinated) to join sympathetic chain.
-post-ganglionic neurons: PARAVERTEBRAL GANGLIA.
-splanchinc nerves pass through the chain without synapsing ending in a
neuron plexus such as a celiac ganglia.
-SIF (small dopaminergic/fluorescent cells) regulate sympathetic ganglia, they are
innervated by preganglionic cholinergic fibers.
-postganglionic acetylcholine is used for sweat glands and BLOOD vessels of
skeletal muscle dilation, arrector pilli muscles
G-protein: GTP replace GDP on the alpha subunit, as a result, the subunit
disassociates from the other two (beta and gamma), alpha activates adenylate

cyclase, the gamma and beta open potassium channels.

Superior cervical ganglion: lower four cranial nerves, pharynx, carotid, and superior
cervical cardiac nerve. (lesion causes Horners syndrome)
Middle and inferior cervical: known at stellate ganglion,
Thoracic chain ganglia and celiac ganglia: send fibers until the left colic flexure (left
colon)
Lumbar and sacral chain ganglia: mesenteric plexus, receive preganglionic from
splanchic nerve, send fibers to below the left colic flexure to the external genetalia.

Parasympathetic nervous system: CN 3,7,9,10 and sacral S2,3,4

Each preganglion synapses with a FEW postganglionic, (symp does many).
Preganglionics Terminate CLOSE to innervated structure (long fibers), whereas in
sympathetic terminate far from structure. (short fibers, send out to many postganglionics)
Post-ganglionics can inhibit transmission or excite the structure. (very short in distance)
CN 7 and 9 come from superior and inferior salivary nuclei of medulla oblongata

Nicotinic AChr: in skeletal muscle, autonomic ganglion, always excitatory.

-Ach binds to nicotinic cholinergic receptors of postganglionic RECEPTORS
-Ach release by postganglionic neurons bind to MUSCARINIC RECPTORS OF
TISSUE.
Somatic sensory system:
Exteroceptive: external senses like vision, hearing, skin and chemical senses
Proprioceptive: provide information about relative position of body
Interoceptive: blood pressure, internal
Nociceptive: pain
Mechanoreceptors: touch and pressure
-Rapidly adapting (aB and A-gamma fibers)
-Meissner corpuscle: hairless skin of palms, two-point discrimination
-Pacinian corpuscle: subcutaneous tissue, vibration, high frequency stimulation
-slowly adapting: mediated by aB fibers
-type 1: fire irregularly
-type 2: regular discharge in response to maintained pressure (Ruffinins end
orgain in hairy skin)
Afferent fibers and joint afferents mediate position sense and kinesthesia.
Spinal cord pathways:
Spinal gray matter:
Posterior marginal nucleus: afferent information
Substantia gelatinosa: relay for pain and temperature
Nucleus proprius: integrates sensory information in conjuction with descending control
Clarkes nucleus: relays limb position to the cerebellum.
Spinal white matter: (myelinated, ascending sensory systems)

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.

-Frequency of sound is dependent on the part of the basilar membrane that is

displaced. Higher pitched sounds produce maximum displacement closer to the
BASE, whereas lower pitched sounds maximally displace the APEX.
-increase in intensity of sounds causes an increase in the displacement of the
basilar membrane and increase of firing of CN 8 fibers.
CN 8 fibers terminate in cochlear nucleus of medulla, and go to superior temperal gyrus,
sound representation is bilateral but each hemisphere localizes sound from the
contralateral auditory hemisphere.
Vestibular system:
Each semicircular canal contains an enlarged ampulla (crista ampullaris) which detects
angular acceleration, caused my hyper or depolarization of hair cells dependent of
movement.
-heat: rotation towards a crista
-cold: away from the crista
The utricle and saccule contain maculae, which sense gravitational pull and linear
acceleration.
Olfaction: hair cells send unmyelinated axos to the cribiform plate and then form the
olfactory never, bipolar cells are the primary neurons of the olfactory system.
-SITE OF TERMINATION is on the ipsilateral olfactory nerve, DOES not
relay in the thalamus.
-projects to the amygdale, olfactory cortex, paraterminal gyrus.
Taste: tractus solitarius, fasciculus solitarius, to the VPM thalamus.
Anterior 2/3: CN 7
Poster 2/3: CN 8
Pharynx/epiglottis: may be carried to the vagus nerve.
MOTOR SYSTEM:
Large pyramidal tract: responsible for voluntary movement on the contralateral side of
the body, while small tract maintains muscle tone.
Upper motor neuron `:
-spasticity or hypertonus: leads to gamma neuron excitation
-patterned paralysis, hyperreflexia (hyperactive reflexes)
-positive Babinksis sign: exaggerated dorsiflexor withdrawal of foot in
response to stiumalation of the outer edge of the plantar surface.
Lower motorn neuron lesions:
-ventral horn and peripheral fibers
-flaccidity since alpha motor neurons are abolished
-hypotonicity, hyporeflexia but nociceptive and sensory may be intact
-muscle wasting, fibrillations (spontaneous contractions)., fasciculations
(repetitive firing of dying motor neurons)
Lesions of the CNS: cause loss of motor activity on the same side, and loss of pain
and temperature sensations of the opposite side.

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.

-estrogens promote protein synthesis, increase HDL and decrease LDL,

responsible for fat deposition, and inhibiting bone resorption.
Androgens are responsible for basal levels of libido and inhibit bone resorption
Menstrutation: estrogen has positive feedback on hypothalamus increasing GnRH, the
surge in LH in combination with high estrogen induces ovulation. (FSH decreases)
Luteal phase: progesterone is secreted, slows down the cyclicity of GnRH, LH and FSH
are constant. The corpus luteum undergoes luetolysis and progesterone and estrogen
levels decrease and the lining of the uterus sheds and the menstrual period begins.
Follicular phase: the estrogen/progesterone ratio is increased and remains high until the
luteal phase where the progesterone is higher. Ovary continues along the fimbrae of the
oviduct and fallopian tube.
Sperm undergoes capacitation once deposited in the vagina, seminal fluid contains
decapicitation factors. Prostatic and seminal vesicular secretions are alkaline and help
neutralize the acid media in the vagina.
HcG is synthesized in the synctiotrophoblast, it is found in high amount of urine in
women who are pregnant. HcG is used in the first trimester for the stimulating the
corpus luteum, not theca granulosa and interna, to produce the estrogen and
progesterone. 10-12 weeks of gestation the placenta takes over the production of
progesterone. (Estrogen DOES Not prepare endometrium, only PROGESTERONE
DOES)
Progesterone during pregnancy CALMS the uterus, by blocking oxytocin receptors, but
activates it during labor.
Estrogen during pregnancy keeps the endometrium functional, stimulates breast tissue,
and increase BLOOD flow to the uterus, and increases the number of progesterone
receptors in the breast.
Placenta does not have 17-a-hydroxylase but can still create DHEA.
Colustrum a thin water fluid that is rich in antibodies from the breast right after
pregnancy.
Oxytocin: uterine contractions and contraction of myoeptithelium due to baby suckling.
Oxytocin causes contractions of the myoepithelium resulting in milk let down, it
does NOT stimulate the milk production, PROLACTIN CAUSES MILK
PRODUCTION.
High levels of prolactin surpress LH and FSH after pregnancy, so as nursing continues
there is a longer surpression of FSH and LH.

RENAL AND URINARY PHYSIOLOGY:

Total body water is 60 percent of body weight, 2/3 of that is INTRAcellular fluid, and
1/3 is extracellular fluid which 75 percent is interstitial and 25 percent is plasma. The
more the adipose tissue the less the body weight is water, because fat has a low
water content.
NaCl is largely in the extracellular compartment.

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.

Countercurrent multiplier: in loops of Henle, resorption of sodium in thick ascending

limb to the vasa recta of medulla.
Urea: freely filtered at glomerulus, approximately half is passively reabsorbed in the
proximal tubule, and can be reabsorbed with ADH in the collecting duct.
Creatinine: not reabsorbed
Glucose: glucose only appears in urine in diabetes and renal glycosuria which there is a
defect in glucose reabsorbtive pump. (similar to amino acids)
Calcium and Phosphate will have opposing effects, if one increases the other decreases in
blood plasma due to reabsorption mechanism.
Sodium reabsorption: majority at proximal tubule and some at ascending loop, very
little at collecting duct and distal tubule.
-ascending limb is impermeable to water
-distal tubule is relatively impermeable to water
-collecting duct and promixal tubule are permeable to water (majority at proximal
tubule). ADH will increase permeability.
ADH effected by: increase osmolality detected by hypothalamus, baroreceptors in
carotid sinus (ninus), aortic arch, atria.
Potassium excretion: caused by acidosis or by aldosterone which reabsorbs sodium and
EXCRETES potassium, diuretics and decrease K+ excretions.
HyPOaldosteronsim: increase sodium loss, decrease cardiac output, decrease renal
flow. Increase potassium retention, cardiac arrythmias due to high K+, increase H+
retention because of coupled mechanism causing acidosis.
H+ ion: actively secreted in proximal tubule, most react wth HC03 the other react with
ammonia and phosphate buffers.
-For every H+ ion secreted, one HC03 is reabsorbed into the blood, so that a large
increase in H+ in blood increases HC03 in the blood
-affected by respiratory acidosis, which increases renal reabsorption of HC03
-aldosterone which causes H+ secretion
-SO KIDNEY HANDLES ACIDOSIS WITH HC03 WHILE LUNG controls C02
If H+, HC03, and Co2 all fall it is respiratory controlled, if H+ and Hc03 go in
different directions, then it is RENAL/METABOLIC controlled.
-alkalosis causes a decrease in H+ secretion by kidneys and decrease reabsorption
of HC03.
Renal circulation: efferent arterioles branch into peritubular capillaries and vasa recta
in the medulla. By increasing or decreasing renal vascular resistance, the kidney assures
itself constant blood flow over a wide range of blood pressures. The regulation occurs by
progressive constriction of afferent arterioles as blood pressure increases, which effects
GFR which increases amount of Na secreted.
-alpha receptors (sympathetic) cause constriction of afferent arteriole.
-Beta receptors of afferent arterioles release rennin when stimulated. Which
causes constriction of efferent arteriole, so pressure is increase even though blood flow is
reduced. Increase in GFR is due to increase in hydrostatic pressure (constriction of
efferent arteriole or vasodilation of afferent arteriole)

-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.

-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 Ttubule 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
From Wikipedia, the free encyclopedia
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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

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

2ATP + HCO3- + NH4+

carbamoyl phosphate + ornithine citrulline + Pi

OTC

mitochondrial

citrulline + aspartate + ATP

argininosuccinate + AMP + PPi

ASS

cytosolic

argininosuccinate

Arg + fumarate

ASL

cytosolic

Arg + H2O

ornithine + urea

ARG1

cytosolic

carbamoyl phosphate + 2ADP + Pi CPS1

Summary reaction:

2 NH3 + CO2 + 4 ATP + aspartate urea + fumarate + 4 ADP + 4 Pi

[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)