1. Patient in CHF. Which substance would be elevated in pulmonary veins? AT-II, cz RAAS is activated and AT-I is converted to AT-II in pulmonary capillaries by ACE.2. Where is PG E1 produced that maintains the patency of Ductus arteriosus? Produced in endothelial cells, mast cells and macrophages. Also an afferent dilator in kidneys.3. Patient with Fever, anorexia, dyspnea. Has Hct=56%, On Xray round lesions are seen in b/l lungs i.e. Cannon ball. Biopsy of lesion shows round Cells with abundant clear cytoplasm. What is the Dx?a. Metastasis from kidneys to lungs is MCC.b. Clue: Hct- 56% due to Increased ectopic EPO from kidneyc. Biopsy shows rounded polygonal cells with abundant clear cytoplasm which points towards Clear cell carcinoma of kidney.d. Travel History may point towards HCC due to Hep B or Hep C.4. Idiopathic Nodular Glomerulosclerosis is a ds linked to longstanding cigarette smoking and hypertension. Obesity is also listed as a contributing factor.5. Fnxns of ADH/Vasopressin:a. Acts on Medullary Collecting tubule to Increase absorption of ureab. Acts on Cortical Collecting tubule to Increase water absorption.6. Citrate Binds with calcium in renal tubules and prevents its precipitation with oxalate or phosphatea. Citrate also increases urinary pH and decreases urate precipitation.b. Citrate acts as Anticoagulant by binding to Calcium and making it unavailable for coagulation pathway.7. Calcium Phosphate and Struvite Stone require ALKALINE pH for precipitation. Acidic environment inhibits their Crystal form. 8. Neuronal ischemiais a well-established characteristic of diabetic neuropathy.9. Mech of nerve damage in DM: NADPH produced by glucose metabolism is used to produce glutathione and Nitric oxide.a. In DM, glucose is converted to Sorbitol by aldolase reductase and it uses NADPH.b. This produces NADPH deficiency and High free oxygen radicals causing nerve damage or retinal cell damage.c. Sorbitol is osmotically active, increase fluid within the cells and osmotic damage occurs leading to fibrosis (e.g. opacity in eye lens)10. Non-enzymatic glycosylation: glucose attaches to amino acids in blood vessel wall later cross linking occurs with collagen facilitates deposition of LDL atherosclerosis11. Sorbitol Fructose by Sorbitol dehydrogenase which replenishes NADPHa. Sorbitol dehydrogenase is present in seminal vesicles (use of fructose by sperm), eye lens.b. In the eye lens, Sorbitol DH prevents the Sorbitol damage under euglycemic conditions only cuz Sorbitol DH has low Vmax. In long standing hyperglycemia, Sorbitol accumulates.c. Sorbitol dehydrogenase is not present in renal papilla, Schwann cells and retina but aldose reductase is.12. The concentration of PAH, Inulin, Creatinine and UREA increase as fluid runs along the PCT, where as the conc. Of BICARBONATEs, amino acids and glucose decrease.13. Metabolic alkalosisa. Loss of Hcl in vomiting: Cl- is deficient in urine due to loss. Kidneys preserve HCO3- to maintain anion gap thus worsening alkalosis. b. Thiazide or loop diuretics: Decrease Na+ delivery to distal tubule, Distal tubule tries to reabsorb Na+ in exchange for K+ , Hypokalemia occursi. H+ moves intracellularly in response to hypokalemiaii. a-intercalated cells reabsorb K+ in exchange with H+ and hence both these steps cause acidosis.c. Aldosterone: causes K+ secretion and hypokalemeia, same mechanism as loop or thiazide diuretics.14. Patient with DKA will have the followinga. Metabolic acidosis: pH MHCIa. TNF-a & TNF-b increases expression of MHC I > MHC II42. NK cells and CTL cells kill by similar mecha. Perforins and granzymesb. Fas ligand and fas receptor on target cellc. TNF a production43. CMV and Cell mediated immunitya. CMV decreases the expression of MHC I so its not recognised by CTLb. Plus it produces a decoy molecule that looks like MHC I to fool the NK cellsc. But our great body has ADCC, IgG binds to the decoy molecule and presents it Fc tail to Fc receptor containing NK cells or CTL.44. Where does IFN-a and IFN-b come from? They are released from virally infected cells to warn the neighbouring cells of virus infection.a. IFN-a and b goto neighbours, produce RNAseL and Protien kinase R(PKR)i. PKR phosphorylates eIF and inhibits translation when cell becomes infected with viral dsRNAii. RNAseL degrades BOTH viral and cellular mRNA.b. IFN-a and IFN-b also enhances activity of NK cells45. Influenza viral vaccine contains haemagglutinin. The antibodies are produced against these antigens, which on real exposure neutralises the real antigens and prevents the entry of virus into cells.a. Oseltamivir acts as viral neuraminidase and prevents the release of virus from the cell.46. CD-16 present on REED-Sternberg cell in Hodgkins lymphoma.47. X-linked hypogammaglobulinemia or Bruton hypo.a. No tyrosine kinase activityb. Increased Pre-B cells(CD19,CD20) in bone marrowc. No Mature B cells in peripheral blood.48. Vaccines produced from capsulated bacteria like Haem. Influenza, Strep. Pneumonia and N. Meningitides are polysaccharide vaccinesa. These are usually covalently bound to protein carriers like diphtheria toxoid or tetanus toxoid b. Advantage: Vaccine gets a T-cell response.49. When parasite invade the mucosa, IgG or IgE bind to antigens and are presented to Eosinophils which release major basic protein that damage the parasites. It is ADCCa. Eosinophils also phagocytose parasitic antigens and express them with MHC-II and stimulate T-helper cells.50. On EMB media, E.coli ferment lactose & give a green metallic sheen.51. Anti-inflammatory cytokines: IL-10 AND TGF-b.a. IL-10 inhibits Th1(decreasing IL-2 and IFN-gamma)b. TGF-b inhibits Th2, CTLs, B-cells52. Wiscott- Aldrich syndrome: ECZEMA, THROMBOCYTOPENIA AND RECURRENT INFECTIONSa. X-linked recessive53. Write about lymph node54. Immature thymocytes cortex of thymus express both MHC I and MHC II.55. GVHD occurs in Bone marrow, liver transplant, blood transfusion and thymus transplantationa. Host Tcells are sensitised against Host.b. Affects liver with jaundice, inc AST/ALTc. Affects GIT with mucosal ulceration, severe diarrhea, pain, N/Vd. Affects skin with maculopapular rashe. Affects vagina, severe pain and scarring, painful sexf. Acute in 100 days56. Maternal immunisation with Tetanus toxoid can prevent neonatal tetanus.57. Silicosis increases susceptibility to M.TB. HOW?a. Impairs the fnxn of MACROPHAGES58. HIV gp120 binds to CD4 and CCR5. If both CCR5 genes are deleted, HIV virus is unable to enter host cell59. No. Of melanocytes black skinned and fair skinned individuals is equal.a. Its the amount of melanin that matters. Melanocytes produce excess melanosomes on exposure to UV light and pass em onto keratinocytes.60. N. gonorrhoea can undergo antigenic variation so infection doesnt provide a long lasting immunity.61. Candida and other fungal infections require cell mediated immunity.62. Kallman syndrome: normally GnRH neurons originate in the olfactory placode;pass through thecribriform plateandthen into olfactory bulb, where the sense of smell is generated.From there they migrate into hypothalamus.a. If there is a KAL-1 or FGFR-1 gene mutation, Failure of migration of such neurons occurs and leads to hypogonadotropic hypogonadism (HH) i.e. low or absent GnRH and absent olfactory bulb (seen on MRI)b. Occurs BOTH in FEMALES AND MALESc. Presentation is delayed puberty i.e. no sec sex characters and ANOSMIA d. Other features: Testicle size is 200 CGG repeats.c. As the no. of repeats increase, it causes the HYPERMETHYLATION of the gene thus inactivating it.d. When lymphocytes of patients are cultured in thymidine and folate depleted culture, FMR1 gene region looks thin constricted (fragile) so called fragile X syndrome89. Chromosomal instability disorders: ds in which chromosomal breaks are seena. Mostly seen in Defective DNA repair mechb. E.g. ATAXIA telangiectasia, BLOOM and FANCONI syn, Xeroderma pigmentosum, and HNPCC90. DNA binding proteins (binding to DNA probes)a. Transcription factors, steroid, thyroid protein, vitamin D receptors, retinoic acid receptors, DNA transcription and replication proteinsb. E.g. N-myc and C-mycc. C-jun and C-fos91. Bcl-2 gene: translocation from chr 18 to chr 14 causes FOLLICULAR LYMPHOMAa. Myc gne: translocation from chr 8 chr 14 results in Burkitts lymphomab. Erb2, Her2 and neu genes: BREAST Cac. Bcr-abl: Philadelphia chr, CMLd. P53: Li-Fraumeni Syn92. Hemophilia A and B are X-linked Recessive Conditionsa. G6PD- X-linked inheritance93. Achondroplasia: AUTOSOMAL Dominanta. FGFR3 gene is defectiveb. Short arms and legs with tibial bowing c. Normal size head, normal GH and IGF-1d. If 2 mutant alleles are present, itll result in DEATH shortly after birth.94. Osteopetrosis: its severe when AR, and Less severe when AD.95. Edward syn: Edward is boys name, HE is felling low.96. For down and turner: arrange all markers alphabeticallyand remember this: LOW LOW HIGH HIGH97. Remember this table98. AFP Is raised in Neural tube defects, Omphalocele99. Huntington ds: Triad of Dementia: memory and cognitive declinea. Chorea: uncontrolled swinging movements of extremitiesb. Behavioural abnormal: AGGRESSIVENESS, apathy and depressionc. Atrophy of caudate nucleus + moderate atrophy of putamend. GABA, Ach and Substance P in striatum.e. NMDA (N-methyl-D-aspartate) binds glutamate and causes neuronal toxicity100. AML: retinoic acid receptor (RAR) gene is translocated from chr 17 chr 15a. It fuses with PML gene and produces a abnormal PML/RAR@ receptor101. Defective EPIDERMAL GROWTH FACTOR RECEPTORS are associated with a. Non small cell lung ca (erbB1)b. Breast ca (erbB2 aka HER2/neu)c. Some ovarian ca102. Defective PDGF in CML103. When a ribosome comes across a STOP codon, No tRNA (charged or uncharged) will interact with it instead RELEASING FACTOR 1 will bind to ribosomes.104. Males born with XXY are phenotypically normal at birth105. Homocystineuria: treat by restricting methionine and supplementing cysteinea. Vascular thrombosesb. Marfanoid features and Ectopis lentisc. Lens is displaced downward and inward where as in MARFAN syn lens is displaced upward and outward.d. Osteoporosis 106. Fetus produces GOWER Hb: 2 epsilon + 2 zeta chains; yolk sac a. Fetal Hb: 2 alpha + 2 gamma; LIVER. Fetal Hb has low affinity for 2,3- BPG cuz it serine residues in place of LYSINE (in Hb A) which decreased the positive charge and decreased binding with negative 2,3-BPGb. FAMILIAL erythrocytosis: methionine replaces lysine on 82 position of beta chain decreasing the binding with 2,3 BPG (similar to HbF)c. Hb A: 2alpha + 2 betad. Hb A2: 2 alpha + 2 delta (normally produced in small quantities in adults)\107. Cheese reaction: excess sympathetic activity due to ingestion of TYRAMINE containing food (old cheese, meats, draft beer)a. It is degraded by MAO in git causing HYPERTENSIVE emergency.b. MAO inhibitors e.g. phenelzine prevents degradation of tyramine.108. Benign fructosuria and hereditary fructose intolerance are due to Fructokinase and Aldolase B deficiency resp.a. Fructokinase def is benigh cuz fructose is converted to fructose-6-phosphate by HEXOKINASE which can be used in glycolysis or converted to G-1-P or G-6-P to be used in Gycogenesis or HMP resp.109. Vit B5 or pantothenic acid: its active form is CoA and is necessary for conversion of pyruvate top Acetyl CoA110. Lead poisoning inhibits ALA-dehydratase and Ferrochelatasea. There is accumulation of ALA and Protoporphyrin IXb. No heme synthesis; Microcytic hypochromic anemia111. Acute intermittent porphyria: def of HMB synthase (hydroxymethylbilane) or Uroporphyrinogen I synthase.a. Acute abdo pain with anxiety, paranoiab. NO PHOTOSENSITIVITY. Urine is port wine color112. mTOR pathway is highly active in CANCER cellsa. Growth factor (e.g. epidermal growth factor) binds on cell receptors this receptor has tyrosine kinase which will autophosphorylate its tyrosine residues activates PI3 kinase which converts PIP2 to PIP3 activates protein kinase B or Akt activates mTOR (mammalian target of rapamycin)b. mTOR will translocate to nucleus and induce genes a/w cell survival, angiogenesis and anti-apoptosisc. mTOR activation is inhibited by PTEN (phosphatase and tension homolog); a tumor suppressor protein. 113. Glycogenolysis maintains blood glucose for about 12-18 hrs and later gluconeogenesis.114. Insulin receptor: transmembrane protein with tyrosine kinase activity phosphorylation of IRS-1 (insulin receptor substrate) activates protein phosphatase-1 dephosphorylation of PFK-2 and glycogen synthase thereby activating them.a. Activates PI3 kinase and GLUT-4 translocation to membrane115. Leucine and lysine are only ketogenic aaa. In patient with PDH deficiency; carbohydrate substrate will lead to lactic acidosis and other symptomsb. So ketogenic diet is advised c. Serine and alanine both will be converted to pyruvate and hence lactate in this cased. Asparagine: broken down into aspartate by asparaginase; converted to OAA by @-ketoglutarate. Since krebs cycle isnt working (no acetyl CoA); no fun of getting OAA from asparagine.116. OAA + Glutamate Aspartate + a-ketoglutaratea. Aspartate + Glutamine Asparagine by asparagine synthase.117. Homeobox genes are Transcriptional regulators; 180 nucleotidesa. Homeobox was initially described in drosophila; mutations in these genes causes limbs and appendages to develop in incorrect locations118. Cocaine causes adrenergic activation causing hyperglycemia, HTN, tachycardia, chest pain, apprehension and diarrhea a. Cocaine inhibits NE uptake from synaptic cleftb. Pupils are dilated with cocaine toxicity.119. Diabetics may develop hypoglycaemia in a vignette; assume over dose of insulin but their NADH to NAD+ ratio would be low120. Gallstones formationa. Infection in biliary tree with ascaris lumbricoides, chlonorchis (opisthorchis) sinensis or E.coli is imp risk factori. They damage the hepatocytes, release of B-glucoronidase, which breaks down bilirubin glucoronides release unconjugated bilirubin and cholesterolii. Calcium binds to form Ca-bilirubinate, Ca-palmitate, Ca-stearate + Cholesterol which participate as stones or BROWN PIGMENT Stones.b. Hemolysis of RBC leads to increased release of bilirubin which cant be bound to glucoronide and is excreted as such in bile; it forms Ca-bilirubinate and ppt as stones: PIGMENT STONES.c. 7@- hydroxylase converts cholesterol to bile acids amd decreases the risk of cholesterol stone formation in GBd. Ratio of bile acid:cholesterol = 20:1 is must to keep cholesterol in liquid form in micelles and prevent stone formation. When ratio drops to 13:1; cholesterol starts precipitating and forms stone121. B-thalassemia is a result of defective alternate splicing, which is part of mRNA processing. This is the first defect in the synthesis of Beta chaina. Second is precipitation of alpha chain affecting membrane stabilityb. Target cells are seen in thalassemia (photo in uworld photos under PBF), sickle cell ds or liver ds.122. snRNP plus proteins forms spliceosomesa. snRNP is formed by RNA polymerase II123. MARFAN syn: defect in fibrilin-1 proteina. Fibrilin-1 makes a scaffolding around the elastin in the MICROTUBULESb. Microtubules are present in suspensory ligament of lens, blood vessels (aorta) and periosteum.124. Superior region of lower lobe of lung shows opacities on xray: MCC is aspiration pneumonia especially if person has H/o stroke with residual hemiparesis. This is called DEPENDENT LUNG CONSOLIDATION125. Intercostals muscle weakness results in atelectasis in posterior lungs.126. Receptors using PHOSPHOINOSITOL system; PIP3 DAG+IP3 PKca. Alpha1 adrenergicb. M1 and M3 cholinergicc. Vasopressin V1 d. Histamine H1e. Oxytocin, TRH, GnRH, AT-II127. Conversion of OAA to PEP uses PEPCK and GTPa. This GTP is produced while converting succinyl CoA succinate by succinyl CoA synthase 128. Citrate is powerful allosteric inhibitor of PFK-1129. NH3 is transported from most tissues in form of GLUTAMINE (most abundant in blood) to kindeya. Kidney has glutaminase to convert it into glutamate and NH3b. From muscle, NH3 travels as ALANINE and is taken up by LIVER 130. N-acetyl glutamate synthase is only present in the liver.131. Pernicious anaemia: classical vignettea. Old woman of northern European descent, mentally slow and LEMON colored (means icteric and anaemic) with smooth shiny tongue (atrophic glossitis) with shuffling broad based gate132. Vit B2 and B6 deficiency have chelosis, glossitis and dermatitis133. Kozak sequence is present in mRNA before the AUG codona. This sequence helps in initiation of translation b. Mutation in this sequence by replacement of Guanine by cytosine affects the initiation of translation.c. It is a/w THALASSEMIA intermedia134. Anaemia severe enough to cause Lactic acidosis will cause fall in pH and shift the OBC to right135. Hartnup disease: AR, chr 5a. Inability to absorb TRYPTOPHAN: a precursor for niacin, serotonin and melatoninb. Niacin forms nicotinamide which is req for absorption of other amino acids in kidney as well as intestines.c. Characterised by aminoaciduria of neutral amino acids. Urine conc of proline, hydroxyproiline and arginine remains unchanged differentiating it from FANCONI syndrome.d. Pellagra like symptoms. ATAXIA. Starts in infancy136. Acute Wernicke encephalopathy: chronic alcoholic if given i/v dextrose will cause use of all the thiamine and cause acute wernicke encephalopathya. It is characterised by opthalmoplegia, nystagmus, ataxia and anterograde amnesia.b. Chronic def causes Korsakoff psychosis characterised by anterograde and retrograde amnesia, lack of insight, apathy and confabulationc. Point to remember: Thiamine deficiency causes decreased activity of PDH and alpha keto DH enzyme, and transketolase & branched chain a-ketoacid DH137. Structure of collagen is Gly-X-Y-Gly-X-Y a. Glycine is the smallest aa; providing collagen a compact structureb. Proline is ring structure, making collagen kink at specific points and providing rigidityc. Photo must see in uworld photosd. Propeptides are C and N terminal extension; DISULPHIDE bond formation occurs in C terminal propeptides which help in formation of a helix; hence form the procollagen.e. Pre-pro alpha chain (with signal sequence) pro-alpha (no signal peptide) hydroxylation of proline and lysine at Y-position glycosylation (with glucose or galactose) of LYSINE only C-teminal propeptide wali side Disulphide bond formation to from procollagen out of the cell cleavage of N and C-terminal propeptides by propeptidases to form TROPOCOLLAGEN many tropocollagen come together to form a fibril lysyl oxidase (Cu2+) forms cross linkages by oxidative deamination of lysine and hydroxylysine138. Arginase converts arginine ornithine + ureaa. Arginase Deficiency: accumulation of arginine in plasma and CSF; causes Spastic paresis of lower limbs and choreoathetoid movements.139. GABA: is formed by decarboxylation of glutamate catalyzed by glutamate decarboxylation.140. Ehler danlos syndrome: collagen formation defect; cross linkages are not formed.a. Terminal polypeptides are disulphide bind rich, these polypeptides are cleaved by procollagen polypeptidase to allow crosslinking b/w different collagen fibrils and make it insoluble and strong.b. Deficiency of lysyl hydroxylase and procollagen peptidase results in hypermobile joints and hyperelastic skin, easy bruising and haemarthrosisc. Procollagen peptidase deficiency results in collagen containing disulphide rich globular domainsd. Lysyl hydroxylase def collagen contains less hydroxylysine residues.141. Galactose galactose-1-P by galactokinasea. Galactose-1-P Glucose-1-P by galactose-1-P uridyl transferase (GALT)b. a/w above rxn; UDP-glucose UDP- galactose same enzyme simultaneouslyc. must see uworld photos: classic galactosemia142. tyrosine melanin; TYROSINASE143. Glycogenolysis : 1daya. Gluconeogenesis: until 1weekb. Ketogenesis: after 1 week of starvation144. Erythrocytes cant use ketones cuz they lack mitochondria 145. Vitamin D and Vit K are absent in BREAST MILKa. Sunlight exposure is especially necessary in dark colour newborns 146. Vitamin C def: haemorrhage, bleeding into joint, subperiosteal hematoma, anemia, perifollicular hemorrhage and corkscrew hair.a. Gingival swelling, periodontal infection, hyperkeratotic papular rash, impaired wound healing.147. See uworld photos: mismatch repair 1 and 2a. Mismatch is recognised by MutS which recruits MutL and form a complexb. MutS and MutL move along the new strand and find the nick which is abnormal;c. They recognise it by absence of adenine methylation which is only present on template standd. They call the endonuclease-1 which cleaves the DNA 5 3 directione. DNA polymerase fills the gap and DNA ligase reseals itf. MutS and MutL are formed by genes MSH2 and MLH1148. Acute GI haemorrhage or Diarrhoea: isotonic loss of fluid from bodya. No change in osmolarity but decrease in ECF compartment. No effect on ICF.149. Adrenal insufficiency: no aldosteronea. Hypertonic loss of NaCl, with some loss of body fluidb. Low osmolarity of ECF, water shifts from ECF ICF150. Hypertonic saline infusion: increase osmolarity of plasma and ECF compartment; also shift of ICF ECF151. Primary polydipsia: increase water intake.a. ECF hypoosmolarity; expansion of both ECF and ICF152. What causes Hyperosmolarity with contraction of ECF and ICFa. Loss of free water more than loss of ionsb. Diabetes insipidus153. Heme synthesis occurs both in mitochondria and cytoplasma. First & last 3 steps occur in the mitochondria154. HbsAg: only enevelop antigen; it forms 22nm tubules and spheres found in the blood secreted by hepatocytesa. HbcAg and HbeAg are nucleocapsid antigens b. HAV is non envelopedc. HCV is enveloped155. Pepsinogen pepsin by HCl or preformed pepsina. Trypsinogen Trypsin by enteropeptidase enzyme156. Secretin: secreted by duodenal cells in response to low pHa. Stimulates the gall and pancreas to secrete HCO3-b. Inhibits the release of Gastrin157. Hypervitaminosis A: a. Acute toxicity: within days. Nausea, vomiting, abd pain, intracranial pressure (papilloedema); and BLURRED VISIONb. Chronic toxicity: ingestion of >25000 IU for 6 years or >100,000 for 6months or morei. Hair loss, blurred vision, osteoporosis and bone pain, hypercalcemia, altered metabolism of vit D, dry skin, hepatomegaly (cuz its stored in liver, causes toxicity), ICP papilloedemac. Teratogenic effects: Microcephaly, cardiac anomalies and foetal death.158. Vitamin C toxicity: diarrhea and abd bloating.a. False negative stool guaic results.b. Vitamin c and calcium oxalate stone are related/159. Elastin: made mostly of GLYCINE-VALINE-ALANINEa. PROLINE and LYSINE is also present; only few of them are hydroxylatedb. Tropoelastin in EC space interacts with fibrillin-1c. LYSINE residues are covalently bound to form DESMOSINE crosslink; these crosslinks form the basis of elastic properties of elastin d. ELASTIN chains DONOT form a triple helix cuz hydroxylation, glycosylation and interchain disulfide bridges at the C terminus are absent in elastin unline collagen.160. Irradiation of neoplastic tissue creates ROS from watera. ROS leads to DNA damage forming DNA double strand breaks.b. Cancer cells have lost the capacity to repair DNA161. Aging and skin wrinkle is due to decreased collagen and elastin an skina. Crosslinking is normal162. Familial dysbetalipoprotenemia or type III hyperlipoprotenemiaa. Mostly due to def of Apo E3 or Apo E4; it is required for uptake of VLDL and Chylomicrons into liverb. Apo E def leads to increased TG and cholesterol in blood.c. Yellow palmar creases, xanthomas (yellow papules) over elbows, knees and buttocks.163. PCR uses primers which bind to flanking regions of DNA to be amplified.a. So sequence of flanking regions must be knownb. Sequence of template to be amplified or cDNA sequence need not be known in PCRc. PCR can only amplify short DNA segments (upto 10 kb)164. Bohr-Haldane effect: Bohr effect occurs in peripheral tissue and Haldane effect occurs in lungs.a. Bohr effect: In peripheral tissue, pCO2 enters the RBC and O2 is released, CO2 + H2O HCO3- + H+; b. HCO3- goes out of RBC in exchange for Cl-; this is called CHLORIDE shiftc. H+ is buffered by arginine present on Hb; doing this decreases the affinity of Hb for RBC.d. HALDANE effect: in lungs, pO2 conc ; HCO3- moves back into RBC in exchange for chloride; HCO3- + H+ H2O + CO2. CO2 moves out of the RBC called Haldane effect165. NADPH cant be used to convert ADP to ATP unlike NADH.166. Thyroid hormone receptors are located within the nucleusa. Whereas receptors for glucocorticoid, adrenocorticoid, androgens and estrogens are present in the cytoplasm167. In PROKARYOTES= photolyase enzyme can excise the thymine dimers formed due to UC light; we need excision endonuclease or UV-endonuclease168. Gestational DM is a result of decreased glucokinase activity a. Glucokinase is the enzyme in beta cells of pancreas required for insulin secretion; as it metabolises glucose, ATP are formed and insulin is released.169. Succinate dehydrogenase: Succinate fumarate; forms FADH2 from FAD.a. Uses riboflavin or Vit B2. 170. HCV is genetically unstable cuz it lacks the 3 5 exonuclease activity in its RNA dependent RNA polymerase171. RASBURICASE and ALLOPURINOL to prevent tumor lysis syndrome.a. Rasburicase is urate oxidase; converts urate allantoin. Excreted in urine.b. Peroxisomes contain uric acid oxidase enzyme.c. Tumor lysis syndrome is hyperuricemia, hyperkalemia (peaked T waves), hypocalcemia and hyperphosphatemia.172. Probenecid is uricosuric agent: given in gout and hyperuricemia.173. Heme biliverdin by heme oxigenasea. Biliverdin is green colored pigment; in hematomas or ecchymoses, this pigment gives green color to skin174. Gouty arthritis: neutrophils phagocytose the negatively birefringent urate crystals and release inflammatory cytokines.a. Colchicines acts by inhibiting neutrophil migration by interfering with microtubule function.175. Leptin hormone is secreted by the fat cellsa. It inhibits the production of neuropeptide Y from arcuate nucleus of hypothalamus; neu. Y is an appetite stimulantb. It stimulates the production of POMC (preopiomelanocortin) from arcuate nulceus; POMC is cleaved to alpha-MSH which inhibits food intake.c. Leptin production increases with increase in fat massd. In obese individuals, sustained inc levels of leptin results in leptin receptor desensitisation; similar to insulin resistance176. HMP shunt occurs in the cytoplasm177. Must read table on glucose transporters in uworld photos178. Hyperammonemia: under normal ammonia levels; NH3 enters the braina. NH3 + glutamate Glutamine; by glutamine synthase within the astrocyte cytoplasmb. Glutamine moves out of the astrocyte into the neuron; is converted back in to glutamate an imp neurotransmitter or glutamine a-ketoglutarate into TCA cyclec. Under NH3 levels, more a-ketoglutarate is converted into glutamate and glutamate further into glutamine, levels of both glutamate and a-ketoglutarated. a-ketoglutarate: poor energy levelse. glutamine: glutamine is osmotically active swelling of cells and mitochondrial dysfnxn.179. OXINDOLE: Is a tryptophan derivative normally formed by the bacteria in gut and CLEARED by LIVER; serum levels in hepatic encephalopathya. Causes sedation, Hypotension, muscle weakness and COMA180. All mRNA post translational modification occur in NUCLEUSa. mRNA is stored in P bodies within the cytoplasm to be used later for protein synthesis181. If a tRNA is incorrectly charged with wrong aa, that aa will be added to growing polypeptide chain.a. Some tRNA-aa synthase enzymes have prrof reading zctivity182. UDP galactose-4-epimerase converts UDP-galactose to UDP-glucose.183. Galactose galactonic acid by galactose oxidase; this acid is used in HMP shunt and is harmless184. TSH, FSH, LH and b-hCG have similar alpha subunita. TSH and b-hCG also have same beta subunitb. So hCG can react with TSH receptors producing hyperthyroidismc. Testicular tumors produce b-hCG and therefore cause hyper-T.185. Familial hypocalciuric hypercalcemia: defective Ca++ sensing by parathyroid cells and renal tubular cells; resulting in failure to suppress PTHa. PTH and Ca++ in this ds186. The complexity of eukaryotic DNA is due to presence of introns in b/w exons187. Secondary lactase deficiency (lactose intolerance) occurs in viral gastroenteritis and celiac sprue.a. Following infection, cells are damaged and replaced by immature cells that contain low amount of lactase.b. Lactose is laso written as galactosyl -1,4-glucose188. Diff b/w phenylketonuria nd malignant phenylketonuriaa. Malignant/atypical phenylketonuria is due to def. of dihydrobiopterin reductasei. BH2 BH4 is catalysed by above enzyme.ii. Both phenylalanine hydroxylase and tyrosine hydroxylase use this enzyme.iii. Results in decreased synthesis of DOPAMINE from tyrosine and high PROLACTIN levels. 189. Cyanide poisoning: a. Nitrites: Hb MetHb; MetHb has high affinity for cyanide, advantage is CN- is sequestered with in blood and isnt given the opportunity to bind cyt a-a3 in mitochondria.b. Thiosulfate: forms thiocyanante and is excreted in urine190. DNA A proteins recognise the origin of replication site191. WHO recommends administration of Vit A to children with measles in areas with widespread vit A deficiencya. Vit A reduces the recovery time from diarrhea and pneumonia192. Vit K def is seen mostly ina. New born infants (low liver reserve, no microbial flora, low content in breast milk)b. Generalised liver dsc. Broad spectrum antibioticsd. Malabsorption syn193. Insulin on its receptor tyrosine kinase causing autophosphorylation IRS-1 is activated by phosphorylation PI3 kinase leads to GLUT4 translocation.a. TNF-alpha: causes insulin resistance; by phosphorylating serine residues on IRS-1 and insulin receptor itself leading to its inactivation.b. Epinephrine, glucagon, FREE FATTY ACIDS and cortisol follow the same mechanism.c. Insulin resistance caused by FFA is termed LIPOTOXICTY d. HDL and LDL have no effect on insulin signallinge. Check photo in uworld photos.194. If a person is going on diet with h/o previous healthy diet and vitamin deficiency symptoms take around 4 years to developa. Its Most likely cobalamin def cuz liver stores are sufficient to last around 3-4 yearsb. Vit A stores last around 6 monthsc. Folic acid lasts 3-4 monthsd. Vit K def requires both dietary and bacterial deficit to develope. Vit A, K, B12, and folic acid are stored in the liver and vit D is stored in the adipose.195. Defective glycolysis ATP deformed and stiff RBC membrane chronic hemolysisa. 95% cases are due to pyruvate kinase def.196. In sickle cell ds, aggregation of Hb molecules occurs cuz:a. Cuz hydrophobic part of beta chain of one molecule fits into complementary site on alpha chain on another molecule under anoxic conditionsb. Hb is prone to sickling in tissues thru which blood passes very slowly like brain muscle and placentac. Normally globin chains are folded such that hydrophobic parts are in the interior and hydrophilic parts are placed exteriorly; alpha helix and beta bends are formed but valine substitution doesnt allow this structure formation.d. Hb S doesnt polymerise when oxygenated and in the presence of HbF197. Mech of insulin release from beta cellsa. Glucose enters the beta cells ATP via glycolysis and TCA cycle ATP binds to K+ ATP channel and closes it; K+ efflux stops, depolarising the cell leading to opening of voltage gated calcium channels Ca++ influx leads to insulin releasei. Sulphonylureas act on K-ATP channels to close it in Type II DM198. Shine-dalgarno sequence is present in the prokaryotic mRNA which recognises the COMPLEMENTARY SEQUENCE on 16S rRNA within the 30S ribosome subunit.a. Once 16S rRNA binds to mRNA, tRNA with fmet binds; followed by 50S ribosomal subunit and initiation of translation. b. Peptidyl transferase a/w 23S rRNA helps in formation of peptide bond formation and transfer of peptide chain from A to P site.c. Streptomycin binds to 30S ribosome and inhibits initiationd. Chloramphenicol binds to peptidyl transferanse required to move aa from A to P site; e. Eryhtomycin and clindamycin inhibit translocation of ribosomes over mRNAf. Tetracyclines inhibit binding of aminoacyl tRNA to A site199. Vimentin protein undergoes change in tissue inflammation:a. Arginine citrulline; this serves as foreign antigen and Igs are produced against this protein.b. This immune response is exaggerated in RA and therefore, anti-CCP antibodies are highly specific for RA.c. RF is Ig against Fc of IgG and is found in 10% of healthy, 30% of pts with SLE so is less specific for RA.200. Early enzyme def in heme synthesis like ALA dehydratase or HMB synthase dont result in PHOTOSensitivity cuz the accumulated metabolites are not porphyrinogens or porphyrins; so they cant react with O2 on exposure to UV light.201. The basis of wobble hypothesis:a. The 5 base of anticodon of tRNA has a diff spatial arrangement than other two bases and inosine may be present at that site, it can pair with uracil, adenine and cytosine.202. JAK-STAT pathway: no intrinsic tyrosine kinase activity.a. Used by Growth hormone, prolactin, cytokines, IL-2 and Colony Stimulating Factorsb. PIGLET: Prolactin, Immunomodulators, GH, G-CSF, Erythropoietin, Thrombopoietinc. Activate intracellular JAK which cross phosphorylate tyrosine residues on the intracellular domain of receptor (autophosphyration)203. Ras-RAF kinase-MAP kinase pathway and mTOR pathway have intrinsic tyrosine kinase activity.a. Ras-RAF-MAP kinase is used by PDGF, EGF, FGF 204. Ubiquitin-proteasome system req to remove misfolded protein.a. Check photo in uworld photosb. Absence of this enzyme causes parkinsons and alzhiemers dsc. PINK-1, parkin and DJ-1 are a/w AR parkinsons