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219 Cards in this Set
- Front
- Back
Synthesis of Cholesterol: Enzymes found in Cytosol + SER. Synthesis everywhere esp. Liver, Intestine, Adrenal cortex, Reproductive sys. What regulates it?
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HMG CoA Reductase;
activated by insulin, statins competitively inhibit it |
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What are the products of the HMG-CoA Reductase?
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Mevalonic Acid
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How is cholesterol broken down?
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It cannot. it is removed by the body by conversion BILE SALT (not acid). Gut bacteria break it down more.
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BILE SALTS are made of:
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type of conjugated BILE ACID: bile salts + phosphatidylcholine
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Primary bile acid:
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Chenodeoxycholic acids: can act as emulsifying agents due to Amphiphatic structure
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Where is BILE ACID synth.?
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Liver= RLS: Cholesterol-7-alpha-hydroxylase; activated by Cholesterol and self regulated
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Bacteria in the intestine convert Primary Bile ACID to:
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Secondary BILE ACID: deoxycholic/lithocholic acids
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Enterohepatic circulation of Bile:
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1* Bile Acid --> Gut (bacteria): change into 2* Bile Acid --> actively reabsorbed(95%)--> carried to liver via Albumin via portal vein--> converted back into Bile salts and secreted back into Bile
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What is Cholelithiasis?
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too much cholesterol over saturates--> not dissolved by Phosphatidylcholine and Bile salts --> forms gallstones
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How does Cholelithiasis develop?
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1.Bile acid not re-ABS
2.obstruction of path 3.kidney dysfunction preventing proper synthesis |
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17-Alpha-Hydroxylase Deficiency
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1. causes back-up increase: 11-deoxycorticosterone + corticosterone= +++ Na Absorption==>Hypernatremia/hypokalemia/metabolic alkalosis ==> w/o 17-ketosteroids: no sex hormones= No secondary sexual characteristics
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17-Alpha-Hydroxylase Deficiency==> Pseudohermaphrodite
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Symptoms: HTN= headaches, tinitus, No menses in females, no external female sexual characteristics
Treated: give them sex steroids |
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5-Alpha-Reductase Deficiency=> Cryptorchidism
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No DHT= testes do not descend and stay in inguinal canal, urination into peritoneum, small penis ==> Pelvic ultrasound + Sex steroids
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Acromegaly signs
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-high GH + Glucose
early: headache + joint pain later: blurred vision + bitemporal hemianopsia -large jaw, hands, feet, HTN, oily skin, organomegaly -young: giant -old: acromegaly |
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Acromegaly
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#1: pituitary tumor: acidophilic adenoma; highly eosinophilic + granulocytic
Tx: remove tumor from Pituitary through nose |
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Acromegaly Treatment
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1. surgery
2. Rx: octreotide or bromocriptine |
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What is the purpose of the Apo-CII that is added to Chylomicrons by HDL?
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activates Lipoprotein Lipase: makes Glycerol(broken down by liver) and Fatty Acid(used by muscle for energy or stored in adipose): absence= too much chylomicrons (or TG)= Type 1 Hyperlipoproteinemia
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How does the remnant chylomicron get recognized by the liver before it its phagocytosed?
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Apo-E
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1. What carries TG to endothelial cells, adipose?
2. What carries TG to liver? 3. What carries TG to tissues? 4. Reverse CE transport to liver from tissue + removing unesterified cholesterol from endothelial cells? |
1. Chylomicrons
2. remnant chylomicrons 3. VLDL 4. HDL |
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What is put into the VLDL as TG are removed from it?
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HDL transfers Cholesteryl Esters by CETP
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What is the fate of VLDL?
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VLDL --> LDL --> tissues: if the receptors for LDL are not working= Type II Hyperlipidemia
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What steroids does the PLACENTA make from cholesterol?
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Estrogen + Progesterone
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What effect do Steroids have on DNA?
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promoter activation --> activate transcription
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What effect does:
1. LH 2. FSH |
1. Testes: Testosterone, Ovaries: Estrogen/Progesterone
************************************* 2. Testes: spermatogenesis, Ovaries: Follicle Growth |
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What is the function of Myoglobin which is found in both heart and muscle?
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1. stores O2
2. carries O2 within muscle cell |
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Shifting of the Oxygen dissociation curve;
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RIGHT= O2 is released into tissues= low pH, high PCO2, high 2,3-BPG
LEFT= CO =Tx: 100% oxygen |
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Sickle Cell Disease
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HbS= point mutation= forms polymers= distorts RBC==>
1. anemia(short RBC life) 2. tissue anoxia 3. Pain when further O2 decrease |
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Where do you see FIBRILLAR type I,II, II collagen?
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tendon, skin, bone, cornea, cartilage, vitreous fluid, blood vessels
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Which cartilage forms networks:
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type IV + VII = basement membrane
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SCURVY from lack of Ascorbic Acid;
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needed for: Hydroxylation of PROLINE and GLYCINE after they are added to alpha-chains of Collagen
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COLLAGEN PROBLEMS
1. Ehlers-Danlos Syndrome 2. Osteogenesis Imperfecta |
1. problem with FIBRILLAR Collage= stretchy skin, loose joints, vascular problems
2. Brittle Bone Disease |
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How is Elastin different from Collagen?
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Fibrillin + Elastin= Elastic Fibers=rubber=> found in lungs, large arteries, ligaments ==> uses PROLINE/LYSINE: fibrillin mutation= MARFAN SYNDROME
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Alpha-1-Anti-Trypsin Deficiency
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A1AT made in LIVER; used in lung to BLOCK Elastase (released from PMN) => absence= lung destruction= EMPHYSEMA= Tx: exogenous A1AT
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glucose transporter isoforms
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GLUT-1 : RBC + BRAIN
GLUT-2: Liver GLUT-4: muscle + Adipose tissue (need Insulin) |
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Glycolysis: Pyruvate Kinase Deficiency
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Only RBC = chronic hemolytic Anemia = changes kinetics
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TCA: Pyruvate Dehydrogenase Deficiency
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Congenital Lactic Acidosis ==> Retardation + Death
Tx: Ketogenic free diet *Arsenic similar results |
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GlucoNEOgenesis: Where are the substrates coming from?
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1. Glycerol <-- TG from adipose tissue
2. lactate <--RBC + exercise Skeletal muscle 3. alpha-Ketoacids <--- metabolism of glucogenic AA |
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Glycogen Metabolism: G6P Deficiency --> hypoglycemia
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Liver cannot make glucose during fasting: Type 1 Glycogen Storage Disease
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What steps are affected by G6P Deficiency= Von Gierke's (not G6PD Def.) ?
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Accumulation of Glycogen: Cannot break it down to Glucose
1. Last step of gluconNEOgenesis 2. Glycogen degredation |
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Does fructose need Insulin to enter cells?
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No
|
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Aldolase B Deficiency
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Cannot eat FRUCTOSE --> death
|
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Cells that do not contain Sorbitol Dehydrogenase can result in?
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Cannot produce Fructose from Sorbitol=> causes osmotic changes:
Retina= cataracts Schwann Cells= Peripheral Neuropathy Kidney= nephropathy |
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Uridyltransferase deficieny
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1. liver damage, retardation, cataracts => accumilation of Galctitol
Tx: No galactose in diet |
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What stimulates the production of Lactose in the mammary glands?
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Prolactin stimulates alpha-lactalbumin
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Pentose Phosphate Pathway --> Need it in Liver/mammary glands (for fatty Acid synthesis) + Adrenal Cortex (steroid synth.)+ RBC (keep glutathione reduced = kills free radicals)
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Makes new NADPH w/o the use of ATP
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Purpose of NADPH:
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1. Make Fatty Acids + Steroids
2. Remove Hydrogen Peroxide 3. Cytochrome P450 system 4. Activate Vitamin D 5. Phagocytosis w/o= chronic granulomas 6. NO synthesis |
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G6PD Deficiency => Low NADPH=> Jaundice in babies after birth
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1. Hemolytic Anemia
2. Heinz Bodies= denatured Hgb 3. Aggravated by: Fava Beans, severe infections, Rx: Anti-malarial drugs 4. Mediterranean is the worst |
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I Cell Disease
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Inability to add phosphate to the mannose residues in N-linked glycoproteins= cannot destroy proteins in lysosomes= over abundance of lysosomal enzymes in cytoplasm because an inability to get them into the lysosomes
|
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In people with CF and neonates where are lipids broken down?
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1. Linguinal + Gastric Lipases not pancreatic derived lipases
|
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What fatty acids must be taken in from the diet?
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Linoleic (makes arachidonic acid)+ LinoleNic acids(omega-3's=fish)
-------- *Cortisol inhibits Phospholipase A2 (cuts AA) + COX-2 ==> no inflammation *ASA= blocks COX-1 and COX-2 *Celecoxib= Blocks only COX-2 |
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What is the regulated step in Fatty Acid synthesis in the cytosol of liver cells?
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acetyl CoA carboxylase makes malonyl CoA <== needs BIOTIN
turned on by: Citrate, insulin |
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How are Fatty Acids stored?
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TG in adipose
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FA degradation= Beta Oxidation=carnitine shuttle (CPT I and II) ==> deficiency=?
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CPT I = liver= cannot use fatty chains for energy= hypoglycemia during fasting
CPT II= heart + skeletal muscle = cardiomyopathy + myoglobinemia= weakness during EXERCISE |
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FA degradation= Beta Oxidation= deficiency in Medium-chain fatty acyl CoA dehydrogenase deficiency (MCAD)=?
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severe hypoglycemia Tx with rich carbs diet
|
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What is Methylmalonic Acedemia and Aciduria?
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No Vitamin B12 for to make succinyl CoA so Methylmalonic CoA builds up= acid = comes from proprionyl-CoA which need Biotin (raw eggs can decrease it)
|
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Phospholipids: what is Cardiolipin?
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found in inner mitochondria= ANTIGENIC = Glycerophospholipid
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Important lipid of Myelin?
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Ceramide used to make sphingomyelin
|
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What is the major lipid of surfactant?
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Dipalmitoyllecithin ==> w/o= Respiratory Distress Syndrome by destroying Type II pneumocytes
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Paroxysmal Nocturnal hemoglobinuria= Acquired
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Absence of GPI= C3b attacks RBC membrane at night(low pH) =+ Hemolytic diseases= aggravated by Fe++ intake
-dark urine from blood -pallor from anemia -Positive Ham's test -high LDH from RBC destruction -Hemosiderin: insoluble Hb product -DVT |
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Inability to breakdown Sphingomyelin because the enzyme is not present increases stores in Brain/BM/Spleen/Liver?
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Niemann-Pick Disease ==> rapid neurodegeneration in Jewish INFANT=
-large lymphnodes -large spleen/liver -cannot see well -cherry-red spot in macula |
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Glycolipids
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Antigenic: found in CNS/PNS myelin
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Ashkenazi Jews
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1. Niemann-Pick Disease= accumilation Sphingomyelin= No sphingomyelinase
2. Gaucher: accumulation of glucosyl-acylsphingosine= No glucocerebrosidase 3. Tay-Sachs: Ganglioside GM2 accumulation= No Hexosaminidase A |
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Inability to RE-absorb CYSTEINE, ORNITHINE, ARGININE, LYSINE in the PCT of the kidney?
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CYSTINUREA=
Cystine= kidney stones Lysine= short stature Tx: low methionine diet, Penicillamine, water |
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Symptoms of too much ammonia from defect in Urea cycle?
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inherited= mental retardation
----- Acquired= tremors slurred speech somnolence cerebral edema blurred vision |
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PKU = deficiency in Phenylalanine Hydroxylase or tetrahydrobiopterin=>
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too much Phenylalanine= Mental retardation=
-cannot talk, walk, grow tall -hyperactive= sweats= smells "mousy" -tremor -small brain -SEIZURES ---- Tx: Tyrosine which it fails to make, no phenylalanine/Aspartamate diet |
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Accumulation of leucine, isoleucine, valine in blood + urine smells sweet like maple syrup ==> babies cannot feed well, vomiting, dehydrated?
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Maple Syrup Disease; no "branched-chain" alpha-ketoacid dehydrogenase ==> mental retardation
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Mental retarded, long arms, long fingers, pectus excavatum, poor visual acuity, osteoporosis, THICK arteries(no fat deposition) in a young child?
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Homocytinuria ==> No Cystathionine Synthase thromboses are major threat!
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Dark spots in sclera, ears, chest, nose bridge, back pain, restricted movement, swelling in knee joints, urine turns black when standing up?
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Alkaptonuria= No Homogentisate oxidase= bad chromosome 3= accumulates HOMOGENTISIC ACID (color)
|
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What is the committed step in making Heme?
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ALA formation by ALA-Synthase: NEEDS: Pyridoxal Phosphate
---- Lead inhibits Ferrochelatase |
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Where is Heme made?
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Liver: variable source
Bone Marrow |
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Heme synthesis problems= Porphyrias==> AD inheritance==>
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Sun exposure ==>chronic skin rash in sun exposed areas
________________________ vs. Acquired Cutanea Porphyria Tarda -Pesticide exposure= hexachlorobenzene -Alcohol makes rashes bad -elevated liver enzymes, urine UROPORPHYRIN, iron levels |
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What happens after HEME is degraded by Macs, packaged into bile and transported by albumin to the GI?
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heme->biliverdin->bilirubin
--------------------------- Stool: Bile (urobilinogen by bacteria) --> Stercobilin (intestinal bacteria)-> out urine: Urobilin--> out |
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Types of Jaundice: too much bilirubin
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1. Hemolytic
2. Obstructive 3. Neonatal: low glucuronylation of bilirubin= no conjugation at early age |
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What is the function of PRPP?
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Makes:
-purines -pyramidines - Purine base salvage from being made into Uric Acid |
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How do Sulfonamides and Trimethoprim work?
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inhibit PURINE synthesis: prevent the growth of rapidly diving microorganisms
|
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Methotrexate
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inhibits purine synthesis= prevents synthesis dTMP (blocks Thymidylate Synthase which needs THF for methyl-group)= no synthesis of DNA and RNA=> stops spread of CA
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Lesch-Nyhan Syndrome: No HGPRT= no salvage of Purines=>?
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High circulating Uric Acid =
joints= GOUT Brain= involuntary movements *self-mutilation |
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How can Gout be prevented from being formed?
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Allopurinol: blocks Xanthine Oxidase
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What causes Secondary Gout?
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-chronic renal insufficiency
-myeloproliferative -alcohol consumption -purine rich foods -Von Gierke disease -fructose intolerance |
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What happens when you accumulate too much ADENOSINE in your body from a lack of Adenosine Deaminase Deficiency?
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you cannot produce DNA = develop Severe Combined Immunodeficiency Disease= no T cells or B cells
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CUT Py synthesis requires this step:
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Carbomoyl Phosphate Synthase II= makes precursors of dUMP so..-->dTMP--> CUT nucleotides
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What hormones counteract Insulin and its effects?
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-Glucagon
-Epinephrine -Cortisol -GH |
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What are some of the most common symptoms from exogenous insulin treatment?
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Hypoglycemia which cause:
-confusion -aberrant behavior -coma *made worse by alcohol use which blocks gluconeogenesis |
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What changes occur in the body during a fasting state?
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Catabolic Period
___________________ Liver: increases Fatty acid oxidation=make acetyl CoA=make ketone bodies= *Feed Brain* Adipose: breaks down TG= makes more Fatty Acids + Glycerol--> liver Muscle: protein is broken down= supplies Amino Acids to liver |
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What must be present together to be called DMII?
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1. Insulin resistance
2. dysfunctional Beta cells = a little insulin is still released preventing ketoacidosis |
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CENTRAL obesity places you at a higher risk for what?
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-HTN
-Insulin resistance -DMII -Dyslipidemia -CHD |
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What type of macronutrients should compose your daily diet?
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1/2 = Carbohydrates: provide energy and fiber
1/3= Fat (should be Monosaturated vs. saturated fats): increase HDL and lower C,LDL,TG 1/10= protein: animal is better than plants= better quality |
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What can result in NEGATIVE nitrogen balance?
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excretions>intake==> Physiological stress=
-trauma -burns -illness -surgery |
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What can result in POSITIVE nitrogen balance?
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Intake>excretion=> growth:
-children -pregnancy -illness recovery |
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What are some disease states that result from bad diets?
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Kwashiorkor= not enough protein
------------------------- Marasmus= LOW calorie diet |
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Water Soluble=FOLIC ACID
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active form= THF
use= make PURINES, Methionine, Thymine Def: Megaloblastic Anemia + Neural Tube defects * Can mask Vitamin B12 Def. at high levels *adults do not get CNS problems |
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Water Soluble=Vitamin B12=no IF
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use= converts Homocysteine to Methionine, makes succinyl CoA
Def: Pernicious Anemia( weakness,SOB due to less O2 carrying), DEMENTIA, SC degeneration=loss of balance, vibratory sense, **+Shillings test, hypersegmented PMN **Adults= IF-Ab |
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Water Soluble=Vitamin C= Ascorbic Acid
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use: antioxidant, pro-collagen hydroxylation,
Def: Scurvy= poor gums, poor wound healing, loose teeth, XR of knees: groundglass *see it in: smokers,oncological patients,alcoholics, infants, elderly |
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Water Soluble=Vitamin B6
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use= cofactor for AA metabolism
Def; Glossitis, neuropathy * made worse by Isoniazid= used for TB |
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Water soluble=Vitamin B1= THIAMINE
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use: cofactor in TCA, PPP,
Def: -BeriBeri= tachycardia, vomiting, convulsions=[dry beribri=demyelination= foot Drop] vs. [wet beriberi=high output heart failure] -Wernicke-Korsakoff= alcoholics=> *apathy, memory loss (destruction of hypothalamus, thalamus, mammillary bodies, PV), nystagmus |
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Water Soluble=NIACIN=Nicotinic Acid
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use= needed to make NADPH
Def; PELLEGRA= Dermatitis (around neck: neckless), Dementia[demyelination], Diarrhea[GI ulcers], posterior columns become degenerated: loss of sensation of pain/touch *can treat hyperlipidemia with high doses *watch out for Carcinoid Syndrome which can use up Tryptophan---> niacin |
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Water Soluble=Vitamin B2=Riboflavin
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use: TCA cycle
Def; dermatitis + angular stomatitis |
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Fat soluble= Vitamin A
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use= reproduction, vision, growth, epithelial tissue diff/maint., gene expression
Def: -Impotence -night blindness= low rhodopsin= early sign -retardation of growth -dry eyes=corneal ulcers=cornea destruction Tox: bone fractures |
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Fat Soluble= Vitamin D
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use= calcium uptake
def= Rickets in kids and Osteomalacia in adults==> soft bones |
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Fat Soluble= Vitamin K
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use= carboxylates glutamate= forms clotting factors= 2,7,9,10
def: newborns>adults*alcoholics*malnutrition= bleeding in knees, gums, vomit **watch out for Antibiotic use also which can destroy Bac which can make some vitamin K ** long PT/PTT but platelets OK |
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Fat Soluble=Vitamin E
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use: antioxidant
def: makes RBC weak=> Hemolytic Anemia |
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What two vitamin deficiencies affect the Spinal Cord?
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Vitamin B12: posterior + lateral columns==> no balance, vibratory, pain, position sense,
________________________________ Niacin: posterior columns==> no sense of pain/touch |
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Xerdoderma Pigmentosum
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UV light damage cannot be fixed --> impaired endonuclease excision repair mechanism --> SCC
|
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Folate Deficiency= need to make DNA/RNA= methyl transfers
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-NO neurologic signs
-hypersegmented PMN's -Megaloblastic Anemia ---------------------- Causes: - alcoholism -pregnancy -TMP-SMX -MTX -Phenytoin -proguanil |
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Two microcytic anemias that show low Iron and Hypochromic RBC's can be differentiated via?
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Iron Def: high Transferrin (transport) + low Ferritin (storage)
------------------------ Chronic Disease: low Transferrin + High Ferritin (stored in macs) |
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Shilling's Test ==> Test for vitamin 12 def. ==>
|
1. inject normal B12 IM + radiolabeled B12 at same time = radiolabeled will be excreted in urine= normal ==> if not then test is repeated with oral IF ==> no pee *B12 then cause of B12 def=
1. Malabsorption Dx: Celiac Dx 2. Whipple's Disease 3. Fish Tape Worm= Diphyllobotrium latum |
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Heinz bodies
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precipitated Hgb= found inside RBC
|
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Bilateral Hemarthrosis= spontaneous => kid
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Hemophilia A => Prolonged PTT (but NOT PT) => NO FACTOR 8
----------------------------- Tx: Factor VIII, Desmopressin, Aminocaproic Acid (pre-op) |
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Hemolytic Anemia + Spherocytosis = Hereditary Spherocytosis= bad spectrin => PIGMENT gallstones
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North European people,
-hemolysis= spleenomeagaly, increase indirect bilirubin |
|
COOMB'S TEST= Direct vs. Indirect = test for Ab's against RBC that might cause Hemolysis
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Direct= agglutination of sample RBC = Ab are bound to RBC surface
-------------------------- Indirect= Test sample Serum for Ab's against RBC= used in pregnancy transfusions |
|
Mathemoglobinemia= BlUE baby= oxidized Hgb= cannot carry O2 well
|
HbF more affected than HbA =>
-Induced by: Dapsone, Benzocaine, dyes -def: NADH mathemegobin reductase Tx: Methylene Blue + O2 |
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Paroxysmal Nocturnal Hemoglobinuria = Test with HAM's TEST= stick RBC's in mild acid= obs. hemolysis==>
|
Hemolysis due to increase compliment binding C3b==> particularly at night when pH is low due to high PCO2 retention==> AM pee is brown-red
*Iron and Heparin might make things worse |
|
Skipped beats?
|
Arrhythmias = hypokalemia
|
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Renal Tubular Acidosis: body becomes ACIDODIC ==> Type 1 and 2 = weakness =>
|
Type 1= DCT= cannot release H+ => Hyperchloremic-HYPOkalemic
---------------------------- Type 2= PCT= cannot re-abs Bicarb= HYPOkalemic ---------------------------- Type 3= low GFR==> cannot make NH3==> cannot get rid of H+ via NH4+ | K+ is OK ------------------------- Type 4= HYPOaldosterone= 1* or Rx = cannot abs Na+ so cannot excrete H+ and w/ HYPERkalemia |
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Necrotic Tissue causes hypocalcemia?
|
Yes, it binds to necrotic tissue
|
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Young Male=> Cannot walk, cannot get up, proximal muscle weakness, LARGE calves(pseudohypertrophy), GOWER's Sign==>
|
Duchenne's Muscular Dystrophy=> Dystrophin gene problem= sarcolemma is not stabilized during contraction=Very PROGRESSIVE (death)= muscle is eventually replaced with fat
|
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Warnicke-Korsakoff Syndrome= Thiamine deficiency= Vitamin B1
|
Warnicke= confusion, ataxia, ophthalmoplegia
------------------- Korsakoff= retrograde (loss prior to incident) + anterograde (loss since incident) amnesia, CONFABULATION (false memory) |
|
-No menstrual period EVER!
-No pubic or axillary hair -Cervix, uterus is not palpable -Vagina ends blindly -Large clitoris |
-Karyotype: XY, 46
-Undescended testes -Inability to respond to Testosterone causes increase in T and LH -Testosterone receptor not responding= Y gene defect => Primary Amenorrhea due to Testicular Feminization ==> remove testes b/c malignancy potential |
|
A woman with a "lack of menorrhea for several months" who IS PREGNANT presents with these physical findings?
|
-breast enlargement
-cervix becomes SOFT and BLUE -palpable masses *LABS= Beta-hCG is + |
|
A Woman with a 4 month history of amenorrhea --> ?
-Athlete -birth control= cycles -no previous history of "missed" periods -Beta-hCG is negative -DECREASED FSH -bleeding does not stop after Progesterone is added -No tumor in Sella |
LOW GnRH= decrease in 15% of weight inhibits hypothalamus= decrease Estrogen= 2* Amenorrhea (but #1 cause is pregnancy)
Advice= gain weight, take oral contraceptive to prevent osteoporosis |
|
Inadequate osteoid formation=> Collagen Type 1 disorder:
|
-multiple bone fractures
-poor healing -Kyphosis + scoliosis -BLUE sclera -CONDUCTION DEAFNESS in both ears -EGGSHELL Cortex= aka thin **Brittle Bone Disease= Osteogenesis Imperfecta |
|
Nausea + Vomiting + Headache + HYPOTENSION in a person with a history binge drinking?
|
elevated levels of Acetaldehyde because Acetaldehyde Dehydrogenase is inhibited by:
1. Alcohol 2. Metronidazole (amebiasis treatment) 3. Cephalosporins **Antabuse effects |
|
Lecithin/sphingomyelin ration less than 2%?
|
Respiratory Distress Syndrome = cyanosis, dyspnea, nasal flaring
-reticular pulmonary infiltrates bilaterally -atelectasis Tx; Steroids such as Betamethasone to pregnant moms= stimulates type II pneumocytes to make Surfactant |
|
Leukocyte Adhesion deficiency II
|
inability to glycosylate ligands (e.g. SELCETINS)=> no immune cell migration==> recurrent life-threatening infections
|
|
Strychnine interferes with what NT?
|
Glycine= result is less inhibition=muscle spasms
|
|
What does glucuronidation acomplish in the liver?
|
makes substrates more water soluble by the addition of glucose
|
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Prion disease involves which pleated sheets that are resistant to degredation?
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Beta= bad= deteriorating dementia + myoclonus
|
|
Marie-Tooth Disease has a defect in which proteins?
|
Heat Shock Proteins= they are chaperons = Nuromuscular disease
|
|
Infants + Chloramphenicol(antibiotic)=
|
Gray Baby Syndrome= fatal shock= inability to conjugate glucoronic acid into Rx
|
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Dip Stick=
|
measures GLUCOSE via glucose oxidase BUT glucose + fructose + galactose are REDUCED i.e Positive in Benedict's Test
|
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Cherry Red mucous membranes + headaches=>
|
CO exposure= high CO-Hgb
|
|
DEAF (CN8) + Renal failure + cataracts=
|
Alport Syndrome= type 4 collagen problem
|
|
Sickle Cell Anemia is a result of what type of muation=?
|
Point mutation= Valine(/) replaces Glutamine(+) in BETA-GLOBULIN @ poisiton 6
|
|
How does a gastrinoma cause diarrhea?
|
gastrin causes an increase in HCL --> lowers the pH which floats down to the Duodenum and denatures enzymes from pancreas= osmotic changes==> diarrhea
|
|
What is the mechanism by which Acetazolamide (non competitive inhibitor=decrease Vmax) can be used to treat glaucoma (cupping of the optic disc, red eye, non reactive pupil)?
|
prevents further aqueous fluid which decreases pressure intraocular
|
|
How is the acid secreted from the parietal cells in the stomach become neutrolized?
|
Pancreas releases Bicarbonate in response to "secretin" w/o stimulation= peptic ulcers
|
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What is not absorbed in Hartnup's Disease?
|
neutral Amino acids
|
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Digestion of these substances results in what absorbable products?
|
Starch= glucose, Lactose= glucose + galactose, sucrose= glucose + fructose
|
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Which ENZYME is produced in the gut epithelium?
|
Enteropeptidase= activates Trypsin (cleaves things in the carboxyl end)
|
|
What enzymes are inhibited by Orlistat?
|
Pancreatic + gastric Lipases
|
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What mechanism is used in the absorption of amino acids from the GI?
|
GGT
|
|
GLUT-1 deficiency= less glucose into CSF=>
|
caues Seizures
|
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How is MODY mamanged?
|
Diet= non progressing hyperglycemia= hexokinase defect
|
|
GLUT-1 vs. GLUT-4
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GLUT-1= requires NO insulin vs. GLUT-4= requires insulin
|
|
NADH that is created in the cytosol cannot cross into the mitochondra except through:
|
1. Glycerol Phosphate Shuttle 2. Malate-aspartate shuttle(generates more ATP)
|
|
Arsenic blocks what?
|
TCA = shows increase levels of pyruvate
|
|
Pyruvate dehydrogenase deficiency (Acetyl CoA pathway)=>
|
babies poorly feed and ataxia: causes lactic acidosis since TCA is blocked made worse by stressor= aka infection, high carb diet vs. Pyruvate decarboxylase deficiency= also lactic acidosis (oxaloacetate pathway blocked)
|
|
Rat poinson FLUOROACETATE blocks the TCA cycle and presents with what symptoms?
|
convulsions, cardiac arrhythmias, death
|
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What vitamins are the source of these energy mediators=>
|
CoA = Pantothetic Acid= B5, NADH=Niacin, FADH2= B2, PP=B6, TPP= Thiamine
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What can cause uncoupling of electron transport causing increase body temperature?
|
Cyanide, 2-4 Dintrophenol, Anesthetics (maignant hyperthermia= halothane, ether, methoxyflurane)
|
|
Chronic granulomatous disease can kill staph or strep?
|
Only STREP (catalase negative= cannot breakdown H2O2)= provides H202 to existing Myeloperoxidase and Cl- ==> makes bleach=kills bacteria vs. Staph which has Catalase which breaks down H202= no bleach
|
|
What compounds inhibit the various complexes of the ETC?
|
Complex I= barbiturates, Complex III= antimycin, Complex IV= cyanide + CO, Complex V= ATPase= anesthetics
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|
Dry cleaner comes in with hepatocelullar necrosis caused by what?
|
CCl4 ==> activated by P450 system
|
|
Familial ALS (ascending paralysis) is associated with what enzyme defect?
|
SOD= superoxide removal
|
|
Pompe's Disease= floppy baby= stores glycogen that it cannot break down where?
|
Lysosomes
|
|
What disease is Specifically related to an inability to make BRANCHES in glycogen in the liver?
|
Anderson Disease
|
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Glycogen storage diseases face off==> cannot break it down at?
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McArdle= muscle, Cori= muscle (dextrin) vs. Pompe= liver
|
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Which Glycogen Storage Diseases result in heart problems in addition to liver problems?
|
Von-GIERKE and Pompe
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F16BP is a key regulatory enzyme inhibited by F2,6BP and ADP?
|
GucoNEOgenesis
|
|
What are some important POINT mutations that cause cancer?
|
1.Ras = GTPase (oncogene) [normally inactivated by NF-1]
2. P53= DNA repair gene (Rb is not= it inhibits growth) *** p53 is degraded by E6 and Rb is degraded by E7 ==> come from HPV |
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What mutations are associated with TRANSLOCAITON which lead to CA?
|
-Burkitt Lymphoma= B cells= 8/14
-Mantel Cell Lymphoma= B cells=11/14 -CML=neutrophils= 9/22 -AML=retinoic acid=wbc=15/17 |
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What are some common CA and the associated gene mutation?
|
-RET= MEN1(ppp)/MEN2(atp)
-HER2= breast vs. BRCA1/2= breast + ovarian -WT-1= Willms tumor -NF-1=neurofibromatosis-1 (schwannomas/acoustic n.) -APC= colon -Rb= retinoblastoma/osteosarcoma -p53(germline)= Li-Fraumeni Syndrome (multiple CA) |
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What are some carcinogens and the CA they develop?
|
-Aniline Dyes= bladder,
-Arsenic= skin, - Chromium/Ni= lung, -Vynil chloride= Angiosarcoma of the liver, -DES= vaginal, -Nitrosamines= Stomach |
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What CA is associated with Asperigilous secreted Aflotoxin B1?
|
Hepatocellular Cancer= molds in grains of developing countries
|
|
What CA is EBV associated with?
|
Burkitt lymphoma + Hodgkin Lymphoma + Nasopharyngeal carcinoma
|
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Which DNA virus is associated with CA?
|
HBV= hepatocellular= #1 worldwide
|
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Which RNA virus is associated with CA?
|
HTLV-1= T Cell Luekemias/lymphomas
|
|
What CA are associated with DEFECTS in DNA repair?
|
-Ataxia Telangiectasia= ionizaiton vs. Bloome Syndrome= UV vs. XP= UV T-dimers,
-Fanconi anemia= cross-linking repair, -HNPCC= DNA mismatch repair, |
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What CA are associated with an inability to MISTMATCH DNA REPAIR?
|
BREAST/OVARIAN + HNPCC
|
|
What blocks VGEF in COLON CA?
|
Avastin
|
|
What are some common CA MARKERS used to follow the progression of cancers?
|
-CEA= colon,
-hGC=trophoblastic tumors + Testicular vs. Alpha-Feto-Protein= liver + testicular, -Calcitonin= medullary thyroid, -CA-125= OVARIAN vs. CA-19= Pancreatic |
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What PREVETNS the BAX influenced release of cytochrome c enzyme from leaving the innner-mitochondria and causing apoptosis in cells?
|
bcl-2 ==> over expressed in FOLLICULAR lymphoma and NOT expressed with HBV
|
|
What does Warfarin block in vitamin K synthesis of clotting factors 2,7,9,10,C/S?
***babies= no flora= no vit K= bleeding!= require vit K shots at birth |
blocks NOT gamma-carboxylase BUT EPOXIDE REDUCTASE which converts K2 --> K1(active)
------------ effect= prevents clotting Vitamin E toxicity can make Warfarin effects greater |
|
What is the biochemical function of the various water soluble vitamins?
|
-B1= decarboxylate= TPP
-B2(FADH2) + B3(NAD+)= Redox -B5=CoA= Acyl transfers -B6=AST/ALT/B3= transamination -B12 (methionine) + Folate(DNA)=methylation ---------- -Biotin=ATP/F.A.=carboxylations -Vit. C= collagen= hydroxylations |
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Why is ZINC so important?
|
A deficiency=>
-poor wound healing -small testes -no facial hair =>cirrhosis |
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What vitamin can chronic alcohol use deplete since it has a short half life in the body?
|
Niacin= Vitamin B3= required for NAD+ synthesis
----------- Also B6 because you need B6 to make B3 through Tyrptophan -------- Reason= you use up 2 NAD+ in breaking down Ethanol to Acetate ----- result= increase NADH= increase Lactate= increase FA synthesis= fatty liver ------ Also High NADH/NAD+ ratio= diverts pyruvate away from gluconeogenesis (low sugar already from not eating)=> hypoglycemia ---- So no Niacin= Pellegra= D,D,D and no B6=hyperirritability |
|
What enzyme is important in Glycolysis?
|
1. Hexokinase/Glucokinase (only liver)
2. Phosphofructokinase 3. Pyruvate Kinase ------VS-------- GlucoNEOgenesis =only: liver/kidney/GI epithelium 1. Pyruvate Carboxylase 2. PEP carboxykinase 3. F1,6-BP 4. Glucose-6-Phosphatase |
|
What is the enzyme that gets you into the TCA?
|
Citrate Synthase--> alpha-ketoglutarate dehydrogenase
|
|
What are the different fates of Pyruvate in Glycolysis?
|
1. Lactate
2. Acetyl-CoA 3. Oxaloacetate= requires Biotin ----- know that Biotin required steps are outside: Glycolysis/TCA ----- incoming from muscle= Alanine = carries NH3 to Liver= makes Urea and in return Glucose is sent back to muscle==> non-functional urea cycle= ammonia intoxication which depletes alpha-ketoglutarate= no ATP (treat with Arginine a TCA substrate) ----- Glycolysis is important in these structures: -RBC, leukocytes, kidney medulla, LENS, testes, CORNEA |
|
What vitamin is required for its product to enter the TCA?
|
Methylmalonyl CoA (use Vitamin B12) --> Succinyl CoA
|
|
What product is used from the UREA cycle to enter the TCA?
|
Fumarate
------- important enzyme in Urea Cycle=> **Ornithine Transcarbamylase |
|
Where do you need Thiamine VS BIOTIN?
|
Thiamine:
1. Transketolase = HMP shunt entering glycolysis 2. PYRUVATE to Acetyl CoA 3. *TCA= succinyl CoA from FA breakdown ---------VS------- BIOTIN: 1. making oxaloacetate from glycolysis 2. making Malonyl CoA i.e for FA 3. making methylmalonyl CoA from FA --> TCA |
|
What is the main difference between Hexokinase found everywhere and Glucokinase(low affinity/high capacity) found only in the liver?
|
Glucokinase has not feedback inhibition by its product G6P= so its always phosphorylates excess glucose which allow it to enter the cell
|
|
What is the rate limiting step in Glycolysis?
|
Phosphofructokinase-1
- activated by F2,6-BP => really powerfull = especially during fasting -----VS----- irreversible process of: -Pyruvate Kinase which is activated by: F-1,6-BP **when PK is not working= hemolytic anemias |
|
What two complexes in metabolism use B1, B2, B3 B5 + Lipoic Acid?
|
Glycolysis= Pyruvate Dehydrogenase Complexes= absence=lactic acidosis=neurologic symptoms=Tx: high fat diet( Lysine/Leucine =ketogenic)
-------------+--------- TCA= alpha-ketoglutarate Dehydrogenase Complex ------ Activated by fasting ----- Arsenic blocks Lipoic Acid= person gets garlic breath, vomits, rice water stools |
|
What does the CORI cycle do?
|
Lactate from muscle is shuttled to the liver to make glucose that way the muscle can work without O2
------- Lactate dehydrogenase is a reversible enzyme |
|
What are the different poisons that can act on the Electron Transport Chain?
-Complex I= takes electrons -Complex II= NO H+ movement -Complex IV= makes H20 -Complex V= makes ATP |
- Rotenone/Cyanide/Antimycin A/ CO=> stop electron transport= no H+ gradient/no ATP
-----VS----- Oligomycin= block ATPase= no ATP made with good H+ gradient -----VS------ Asprin/2,4-Dintrophenol= uncouple= prevent H+ permeability=no ATP but electron transport continues=> increases heat |
|
What are the 2 functions of the HMP shunt?
|
1. Make FA/steroids= Oxidative= not reversible =G6PD
----Vs------ 2. Make energy products= non-oxidative |
|
How does Fructose accumulation cause Hypoglycemia?
|
blocks glucoNEOgenesis + Glycogenolysis = Aldolase B problem
--- stop SUCROSE intake ----VS--- No Lactose( glucose/galactose) with Galactosemia = increase Galactose-1-P INSIDE cell ----BUT---- if you have Galactokinase Deficiency you increase Galactose in circulation =>>> BOTH leads to Galactitol= toxic |
|
Which AA are found in histones that wrap around NEGATIVELY charged DNA?
|
Arg + Lys = basic
|
|
What is the rate limiting step in the UREA cycle?
|
Carbamoyl phosphate synthase I
|
|
What is the mechanism for giving Arginine in Hyperammonemia?
|
increases in NH3 can increase the use of alpha-ketoglutarate which halts the TCA cycle and you get a decrease in ATP. You can fix this by giving Arginine which will provoke the UREA CYCLE in the liver to increase urea synthesis but also increase Fumarate byproduct which can enter the TCA and make some ATP
|
|
What essential amino acid is reduced if you have depigmentation, HYPOthyroidism, and adrenal MEDULLA hypotrophy?
|
Phenylalanine which makes Tyrosine
--------VS------ High levels of Phenylalanine= toxic=>PKU=musty odor with mental retardation at birth==> DO NOT give NUTRA-SEET (a lot of phenylalanine) --BUT-- give them Tyrosine -----VS---- too much Tyrosine=> Alkaptonuria=> Black pee when standing= benign ==> problem is in breakdown of Tyrosine by Homogentisic acid oxidase ----VS----- No Melanin= No enzyme (Tyrosinase) or Tyrosine uptake= ALBINISM= issue could be with no NEURAL CREST CELL migration= increase risk of skin cancer |
|
What essential AA are you missing if you have Depression, circadian rhythm problems, Dementia, Diarrhea, Dermatitis (Pellegra) or carcinoid Syndrome?
|
Tryptophan -->makes Niacin,Serotonin, Melatonin
|
|
A deficiency in what AA will cause ANEMIA?
|
Glycine= need it for Heme synthesis
|
|
What are the causes of Homocytinuria which can cause TALLNESS, retardation, kyphosis, changes in the lens of the eye and EARLY ATHEROSCLEROSIS?
|
Acquired=> You need two vitamin deficiencies Vitamin B12 + B6
-------------------- Genetic deficiencies= 1. Cystathionine synthase 2. Low affinity for B6 3. Methionine synthase ---------------- Treat with high levels of Cysteine =but may cause kidney stones |
|
What type of receptor is involved with these hormones?
|
PLC: TRH, GRH, ADH/OXT
------VS-------- cAMP: CRH, LH/FSH, TSH, hCG, V2, Calcitonin, Beta-2, alpha 1/2 -----VS------- cGMP: ANP, EDRF, NO ---VS----- TK: insulin. Prolactin, GH, Insulin like Growth hormone ----VS---- Steroids: aldosterone |
|
What is Cretinism?
|
Fetal Hypothyroidism= problems with thyroxine formation
|
|
Biomolecular techniques with DNA==>
|
FISH= fluorescent probe to SPECIFIC GENE of interest= used to localize
----------VS-------- 1. Sequencing: Dideoxynucleotides= stops growing strands of DNA=Gel electrophoresis to seperate by size=allows you to read base sequences 2. Allele Specific oligonucleotide probe= specific labeled DNA probe= look for specific mutations 3.Southern Blot= separate DNA with electrophoresis= add label + expose 4. PCR -----------------VS------- ELISA= look for antibodies or antigens are present or immune systems reacts to it in blood= very specific -----------VS------------- Western Blot= look for proteins by adding known antibodies |
|
How does SCID (low T + B lymphocytes) develop= bubble boy?
|
DNA synthesis is inhibited which prevents lymphocytes from being made= cause is a deficiency in ADA which causes an increase in Adenosine which stops DNA synthesis through feedback inhibition
***Purine salvage deficiency**** |
|
What causes an increase in Uric Acid = Lesch Nyhan Syndrome?
|
usually Purines (guanine) are salvaged but the absence of enzyme(HGPRTase) prevents it and thus are destroyed by Xanthine Oxidase==> SELF MUTILATION, aggresion, GOUT
|
|
Glucose transport into cells is different varies in what way?
|
GLUT-1= brain, RBC, Kidney, Liver, GI, Cornea= taken up for energy
----VS----- GLUT-4 + Insulin= storage=> Adipose + Muscle -------VS------- GLUT-2= Pancreas=Beta-cells= insulin release ***** GI has alternative forms of getting Glucose in |
|
How is Glycogen controlled?
|
glucose-1-P=> add UDP=> branches=> glycogen
----VS---- phosphorylation=>debranch= glucose-1-P ---------------- Inability to degrade causes Hypoglycemia during fasting= 1. Von Gierke's= no phosphorylation= Large LIVER, 2. Pompe's= alpha-1,4 is not working=HEART gets big, 3. Cori's= alpha-1,6, 4. McArdles= Specific to Skeletal Muscle=PAIN!!! |
|
What are the only two XR LYSOSOMAL storage diseases?
***Cerebroside (final product) is needed to make Myelin |
BOYS ONLY ==>
1. Fabry's = Sphingoliposes, 2. Hunter's= Mucopolysaccharidoses ------VS---- - the rest which are AR |
|
An increase in Heparan Sulfate within Lysosomes can be differientiated in what way?
|
Hurler's= corneal opacities + Gargoylism
---VS--- Hunter's= NO opacities -----VS---- Metachromic Leukodystrophy= which is Cerebroside Sulfate= Ataxia/Dementia from CNS/PNS demyelination |
|
Which is the only Lysosomal storage disease which besides progressive neurodegeneration, hepatospleenomegaly or cherry red spots on feet attacks the BONES?
|
Gaucher's= necrosis of femur w/o infection present
|
|
What are the shuttles in the inner-mitochondrial membrane invovled with Fatty Acids?
|
Citrate Shuttle=cytoplasm=makes FA=Acetyl-CoA
-------VS----- Carnitine Shuttle=mitochondria= Beta-Oxidation= Acyl-CoA= non=> toxicity |
|
During severe starvation in a person with FRUITY breath which is the ONLY ketone made by the liver via HMG-CoA that can be detected by a URINE TEST?
|
Acetoacetate
----- NOT= beta-hydroxybutyrate |
|
absence in the Apolipoprotein-AI causes an increase in Free Cholesterol and NO HDL. What is it?
|
Tangier's Disease= orange tonsills + large spleen
-------VS------ Absence of LCAT (esterifies cholesterol in VLDL)=> FISH EYES + hemolytic anemia that can cause ESRD **** AI activates LCAT ------VS----- no CII or Lipoprotein Lipase=> Familial hyperChylomicronemia= too much cholesterol/TG ---Similar too------ Dysbetalipoproteinemia= also high TG/Cholesterol= NO Apo E |
|
What does an excess of chylomicrons, VLDL, IDL, LDL cause to the skin?
|
Eruptive Xanthomas= Yellow papules
-----VS----- familial hyperCHOLESTEROLemia= no LDL receptor=too much LDL= too much cholesterol=> Achillis Tendon Xanthomas usually with MI in KIDS= sudden death ------VS----- #1= Mixed Hyper-TG-emia= VLDL clearance/production issues= high VLDL + chylomicrons= high TG + Cholesterol= NO XANTHOMAS |
|
What intermediate is accumilated with LEAD poisoning?
|
ALA +COPROporhyrin
|
|
What intermediates accumilate in the URINE with Acute Intermediate Porphyria in the process of trying to make HEME?
|
Porphobilinogen + gamma-ALA
--------VS------- Porphyria Cutanea Tarda= Uroporphyrin = tea color pee ---------- Common symptoms= Painful abdomen, Pink Urine, Polyneuropathy, Psych issues, Precipitation of Rx -----VS---- normal heme breakdown= UROBILIN ----VS--- Poopoo heme= urobilinogen (small amounts in the pee) ------ Obstructive Liver Disease= in urine= high bilirubin + low urobilinogen |
|
What is the oxidized form of Hemeglobin which has a higher affnity to CYANIDE?
|
Methemoglobin= Fe+++ =treat with methylene blue make Fe++ again
-------- with cyanide poisoning you want to make more methemoglobin to clean cyanide up=> use NITRATES |
|
What is the difference between ACUTE and CHRONIC pancreatitis in regards to enzymes?
|
ACUTE= inapporpiate enzyme activation because of blockage= alcohol/drugs/trauma
------VS----- CHRONIC= exhaustion of enzyme reserves from repeated bouts of acute pancreatitis |
|
What are Factor V Leiden thrombophilia at high risk if they are homozygotes>heterozygotes?
|
DVT at young ages= strong family finding
|
|
What disease makes a lot of new blood vessels through out the body especially in the RETINA/BRAIN/Spinal Cord?
|
Von-Hippel-Lindau Syndrome=VHL(chromsome 3)= angiomas +hemangioblastomas= BiLATERAL RENAL CELL CARCINOMAS
|
|
What is the difference between FRUCTOSE intolerance amongst the two known enzymes?
|
Fructokinase= increase circulating fructose= benign
---------VS------ Aldolase B= decrease free phosphate because F-1-P builds up and uses it all up |
|
What drugs can be used to treat common overdoses?
|
Organophosphates= Atropine
------ ASPRIN= N-Acetylcystein= works on metabolites ------ Opioids= Nalaxone ------ Heparin= PROTAMIDE= binds to negative-charged heparin ----- ETOH= use Thiamine first --> saline |
|
Chromosomes and associated Diseases=>AUTOSOMAL DOMINANT=>
|
22= neurofibramatosis 2= bilateral juvinal cataracts
---- 3= Von-Hippel=Lindau Disease ---- 4= Huntington's Disease= low GABA/ACh @ caudate ----- 5= FAP= colon cancer 5=deletion= Cri-Du-chat=retarded meaow ----- 16= Adult Polyc Cystic Kidney Disease= APKD1= bilateral = berry aneurysms ----- 17= Neurofibramatosis 1= cafe-au-lait spots= pigmented eye harmatomas=a lot of tumors=pheochromocytomas= scoliosis |