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- What region of the brain is impt for regulation of appetite and thrist
- =hypothalamus 1. Appetite -regions for both satiety (ventromedial nucleus) and feeding (lateral hypothalamus) -stimulation feeding center -> eat -stimulate satiety center -> stop eating 2. Thirst -influenced by ECF volume, plasma osmolality, other factors (ex dryness of mouth)
- What 2 cranial nerves trigger swallowing?
- =reflex -CN IX and CN X -Components 1. initiation -voluntary via bolus of food propelled into pharynx 2. Involuntary contraction -pharyngeal muscles push bolus into esophagus 3. Automatic closure of glottis 4. peristaltic contraction of esophagus -upper esophageal sphincter and lower esophageal sphincter transiently relax to allow passage of food
- True or false: the stomach is a site of major chemical digestion of food
- -false -it only does a little chemical digestion -main fxns: 1. storage 2. mixing 3. controlled emptying
- Name 3 substances produced by colonic bacteria (normal flora)
- 1. Vit K 2. complex B vitamins 3. folic acid
- Hexokinase is associated w/what metabolic process?
- Glycosis -phosphorylate glucose (1st step) -hexokinase is found in all cells -uses ATP to add on the phosphate group
- Glucokinase is associated w/what metabolic process?
- -Glycolysis -found in liver ONLY -phosphorylates glucose -uses ATP to add on the phosphate group
- Phosphofructokinase is associated w/what metabolic process?
- -glycolysis -uses ATP to add phosphate group -makes fructose1,6bisphosphate -rate limiting step of glycolysis -activated by AMP -inhibited by ATP, citrate
- Pyruvate kinase is associated w/what metabolic process?
- -glycolysis -catalyzes formation of pyruvate and ATP -Can be inhibited by: 1. phosphorylation 2. ATP, acetyl-CoA, alanine (allosteric)
- Lactate dehydrogenase is associated w/what metabolic process?
- -glycolysis (but ONLY under anaerobic conditions) -reduce pyruvate to lactate -regenerates NAD+ (impt so glycosis can continue)
- Pyruvate dehydrogenase is associated w/what metabolic process?
- -making pyruvate into acetyl CoA (so it can be broken down by the Krebs cycle); irreversible rxn -multienzyme complex (3 diff parts) -5 coenzymes required -inactivated by: 1. phosphorylation 2. allosteric inhibitors (acetylCoA, NADH) -inherited and acquired def
- Pyruvate carboxylase is associated w/what metabolic process?
- =gluconeogenesis -converts pyruvate -> oxaloacetate -need w/ PEPCK to overcome irreversible step of glycosis
- PEPCK is associated w/what metabolic process?
- =gluconeogenesis -converts oxaloacetate back into PEP -works w/pyruvate carboxylase to overcome irreversible step in glycolysis
- Glucose-6-phosphatase is associated w/what metabolic process?
- =gluconeogenesis -removes phosphate group from glucose -> free glucose -found ONLY in liver, kidney, intestinal epithelium -NOT in SKM -def=von Gierke disease
- Glycogen phosphorylase is associated w/what metabolic process?
- =glycogenolysis -breaks down glycogen (removes 1 glucose unit) by adding an inorganic phosphate
- Glycogen synthase is associated w/what metabolic process?
- =glycogen synthesis -takes glucose from UDP-glucose and adds it to existing glycogen chain or glycogenin (protein primer) -activated by insulin, glucose -inhibited by glucagon, epinephrine
- UDP-glucose pyrophosphorylase is associated w/what metabolic process?
- =glycogen synthesis -sticks glucose on a high energy carrier (UTP) -makes UDP-glucose that can then act as substrate to add glucose to glycogen
- Fructose 1,6 bisphosphatase is associated w/what metabolic process?
- =gluconeogenesis -hydrolysis of F1,6bisphosphate to F6P and P -opposing enzyme to PFK and regulated by same components
- What is the purpose of the hexose monophosphate shunt?
- 1. Make NADPH for use in anabolic processes (FA biosynthesis) 2. Produce ribose-5-P for nucleotide synthesis -rxns occur in the cytoplasm -rxns do NOT produce or consume ATP -rxns do use glucose (G6P), generate CO2, and fructose6P (gets returned to glycolysis)
- Transaldolase and transketolase are associated w/what metabolic process?
- =hexose monophosphate shunt -help recycle the excess pentoses produced by the shunt back into fructose6P -F6P can go back to glycolysis
- Glucose-6-P dehydrogenase (G6PD) is associated w/what metabolic process?
- =hexose monophosphate shunt -catalyzes first step in using glucose6P from glycolysis to generate NADPH and ribose-5-P -rate limiting step -def: hemolytic anemia w/Heinz bodies in RBCs
- Fructokinase is associated w/what metabolic process?
- =fructose metabolism -adds phosphate group to fructose; -first step in converting fructose to intermediates that can be used in glycolysis, gluconeogenesis -def=essential fructosuria (benign condition where fructose not metabolized and found in blood and urine intact)
- Aldolase B is associated w/what metabolic process?
- =fructose metabolism -breaks fructose1P into 2 intermediates that can be used by gluconeogenesis and glycolysis -def=hereditary fructose intolerance -accumulate F1P -> shut down glycogenolysis and gluconeogenesis -severe hypoglycemia and vomiting -effects reversed by removing fructose and sucrose from diet
- Galactokinase and galactosse-1-phosphate uridyl transferase are associated w/what metabolic process?
- =galactose metabolism -convert galactose to glucose1P which can be used in other metabolic pathways -def in either enzyme ->galactosemia -def -> galactose accumulates -> converted to galactiol in nervous system (MR) and eyes (cataracts) -w/ uridyl transferase alse get hepatomegaly -tx: remove galactose and lactose from diet
- What is NADPH used for?
- 1. Reducing biosynthetic processes (synthesizing XOL, FAs, steroid hormones) 2. Keeps glutathione in RBCs in reduced form (prevents hemolysis) 3. Used in bactericidal killing of microbes by phagocytes (oxidative burst)
- What are the 2 essential fatty acids?
- Essential FA=must be acquired from diet 1. Linoleic acid (18C, 2 db) -can be converted into arachadonic acid (20C) 2. Linolenic acid (18C, 3 db) -
- Arachadonic acid is a: a. nucleic acid b. triacylglycerol c. fatty acid d. amino acid
- =fatty acid -20C -produced from linoleic acid (essential FA acquired in diet) -impt precursor for many local hormones (PGs, thromboxanes, LTs)
- Acetoacetic acid and betahydroxybutyric acid are both: a. fatty acids b. amino acids c. ketone bodies d. steroid hormone precursors
- =ketone bodies -synthesized from FA and amino acids by liver during starvation, diabetic ketoacidosis -act as soluble metabolic fuel for heart, brain, SKM, kidney -excreted in urine -excess ketones=fruity breath
- Dipalmitoylphosphatidylcholine is a: a. fatty acid b. triacylglycerol c. sphingolipid d. phospholipid e. glycoprotein
- =phospholipid =surfactant -phospholipids are distinguished by their polar head group -in surfactant, the polar head group=choline
- Cerebrosides, sphingomyelin, sulfatide, globoside and ganglioside are all examples of ________.
- =sphingolipids/glycolipids -all contain ceramide (sphingosine linked to FA) -sphingolipids differentiated by X group attached to the ceramide
- Compare the functions of LDL and HDL
- LDL (aka bad XOL) 1. transports XOL to extrahepatic tissues HDL (aka good XOL) 1. circulating resevoir for apoproteins 2. reverse XOL transport -move XOL from extrahepatic tissues to the liver
- Lipoprotein lipase is associated w/what metabolic process?
- =Triglyercide (TG) transport -degrades TG circulating in chylomicrons and VLDLs -CII (apolipoprotein) is required cofactor -def -> increased amounts of chylomicrons (pancreatitis, lipemia retinalis, erruptive xanthomas)
- Lecithin cholesterol acyltransferase (LCAT) is associated w/ what metabolic process?
- =reverse XOL trasport -catalyzes esterification of XOL that goes into HDL and is transported from periphery -> liver
- What's a myeloid stem cell?
- =blood stem cell that can give rise to 3 types of blood cells 1. RBCs 2. Granulocytes (neutrophils, basophils, eosinophils) 3. plts -derived from plasma fragmentation of megakaryocytes
- Granulocytes include all of the following EXCEPT: a. basophils b. eosinophils c. macrophages d. lymphocytes e. neutrophils f. 2 or more of the above
- =f=macrophages and lymphocytes -mphages and lymphocytes =agranulocytes b/c they lack specific granules (vs basophils, PMNs, eosinophils that have characteristic granules)
- Name 4 types of pharmacologic drugs that do NOT act through cell receptors
- 1. Antacids -neutralize stomach acids 2. Chelating drugs -bind metallic ions 3. Osmotically active drugs -diuretics (mannitol), cathartics (methylcellulose) 4. Volatile general anesthetics -cause reversible changes in synaptic fxn from within cell membrane -drug potency correlates with lipid solubility
- Contrast efficacy and potency
- Efficacy -maximum response an agonist can produce -ex. antagonists bind to R but do NOT stimulate them = NO efficacy! Potency -measure of how much drug is required to produce a given effect -less drug required -> more potent -measured by the ED50 (concentration of drug that elicits 50% response)
- Define therapeutic index
- =describes the safety of a drug -higher TI means drug is safer =ratio of dose of drug required to produce a toxic (TD50) effect or a lethal (LD50) effect to the dose needed for a therapeutic effect (ED50) =TD50/ED50 OR LD50/ED50
- Define bioavailability of a drug
- =the fraction of drug administered that reaches the systemic circulation -if bioavail=100% -> drug given IV -if bioavail <100% -> drug given other route =F
- Define first pass metabolism
- =Drugs absorbed from GI tract enter portal circulation and are subject to inactivation by liver before reaching systemic circulation -> decreased bioavailability
- Which of the following is FALSE about orally administered drugs a. they must be lipophilic b. they have 100% bioavailability c. they can be subject to first pass metabolism d. They must be resistant to gastric acid, digestive enzymes, and GI flora
- =B -NOT 100% bioavail b/c imperfect absorption +/- first pass metabolism
- Where is sublingual administration impt for drugs needing rapid onset of action?
- -b/c you bypass first pass metabolism and get straight into systemic venous circulation -ex. nitroglycerin
- What route of drug administration is contra-indicated in pts on anticoagulants?
- -intramuscular injections
- Intrathecal administration of drugs refers to injecting drugs into the __________ or ______________.
- -subarachnoid space or ventricular systme -bypasses blood brain barrier and blood CSF barrier
- Define volume of distribution
- =apparent volume into which a drug distributes =total drug in body (g) ------------------ plasma drug concentration (g/L) -the greater the Vd the slower the elimination rate
- How do plasma proteins account for drug-drug interactions?
- -many drugs like to bind to plasma proteins (ex albumin) and several drugs can compete for same site -if administer 2 highly protein bound drugs, one drug may displace the other drug -> higher blood concentrations of displaced drug -> side effects or toxicity
- Where are most drugs metabolized?
- -in the smooth ER of hepatocytes
- Contrast Phase I and Phase II drug metabolism
- Most drug metabolism and biotransformation occurs in the liver Phase I -Oxidation -Reduction -hydrolysis Phase II -endogenous substance added onto the drug -results in: 1. inactivation of the drug 2. drug more hydrophillic -> easier to excrete -glucuronidation -sulfation -acetylation -addition of AA -conjugated drugs secreted in bile, can be: 1. released in feces 2. reabsorbed then excreted in urine
- Name 5 factors affecting liver metabolism of drugs
- 1. Age -very young and old have impaired met 2. Genetics 3. Hepatic insufficiency 4. Drug interactions -CYP inhibitors -> delay metabolism of a drug -CYP inducers -> speed up metabolism of a drug 5. Hepatic blood flow -decreased blood flow can impair metabolism
- What's the difference between zero order and first order kinetics?
- Zero order -drug decreases at a constant rate regardless of plasma concentration -ex. ethanol First order -drug eliminated in rate proportional to plasma drug concentration -rate of elimination can be described by: 1. half life (t1/2) 2. Elimination constant (ke)
- Define clearance of a drug
- =volume of blood that can be completely cleared of a drug per unit time =ke x Vd = (0.7/t1/2)
- How long does it take drugs to be eliminated from the body?
- -depends on half life -takes 4-5 times the half life to reach accumulation steady state in body -likewise, it takes 4-5 half lives of drug to be almost completely eliminated (approx 94%) -half life is used to determine dosing interval needed to get desired level of drug -if long half life, give large loading dose and smaller maintainence doses
- Name 4 ways to prolong the action of a drug
- 1. Frequent doses 2. Time released tablets 3. slow excretion of the drug 4. inhibit metabolism (ex block CYP)
- What is the significance of the hepatoduodenal ligament?
- =part of the lesser omentum (an abdominal mesentery--double layered serous membrane) -Impt b/c contains the portal triad: 1. hepatic artery 2. hepatic vein 3. common bile duct
- Name the structures of the foregut
- 1. Esophagus (distal to respiratory diverticulum) 2. stomach 3. liver 4. gallbladder 5. pancreas 6. duodenum (to entry of common bile duct) -all share common: 1. Blood supply arterial= celiac trunk 2. lymphatics -drain to celiac nodes (on celiac artery) 3. innervation -preganglion parasympthathetic: vagus -preganglionic sympathetic: thoracic splanchic nerves via celiac plexus
- Name 3 unpaired branches off aorta that constitute major blood supply to abdomen.
- 1. Celiac trunk -foregut structures + spleen 2. Superior mesenteric artery -midgut structures 3. Hindgut structures -inferior mesenteric artery
- Name the structures of the midgut
- 1. Duodenum after entry of common bile duct 2. Jejunum & ileum 3. cecum 4. appendix 5. ascending colon 6. 2/3 of transverse colon -All share a common: 1. Blood supply -Arterial: superior mesenteric artery 2. Innervation -preganglionic parasympathetic: vagus -preganglionic sympathetic: thoracic splanchnic via superior mesenteric plexus
- Name the structures of the hindgut
- 1. distal 1/3 of transverse colon 2. descending colon 3. sigmoid colon 4. upper 1/3 of rectum -All share a common: 1. Blood supply Arterial: inferior mesenteric artery 2. Innervation Preganglionic parasympathetic: sacral SC 2,3,4 via pelvic splanchnic -preganglionic sympathetic:lumbar sympathic trunk via hypogastric and inferior mesenteric plexuses
- What is the significance of the esophageal branch of left gastric vein?
- -acts as a portal caval anastomoses -connects up with superior mesenteric vein -impt alternate route to return blood in event of liver problems (ex cirrhosis) -but can get clogged up, varicose, and even rupture b/c they're not used to high volume venous blood flow through them