Random Review Flashcards
1
Q
Stellate Cells
A
Perisunusoidal cells (pericytes) that secrete TGF-beta and are responsible for the disruption of the liver architecture in cirrhosis
2
Q
Reye syndrome mechanism
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Aspirin metabolites decrease beta oxidation by reversible inhibition of mitochondrial enzymes
3
Q
Emphysema (centri vs panacinar) location predominance
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Centriacinar (tobacco) - upper lobes, Panacinar (a1at) - lower lobes
4
Q
Tx for Crigler-Najjar Type II (less severe)
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Phenobarbital – induces liver enzyme synthesis
5
Q
Epinephrine metabolites within lysosomes?
A
Dubin-Johnson syndrome
6
Q
Wilsons disease causing blood issues?
A
Yes – hemolytic anemia
7
Q
p-ANCA
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UC, Churg-Strauss, PSC, Microscopic polyangitis, RA, occasionally polyarteritis nodosa
8
Q
Metanephric mesenchyme
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Glomerulus to DCT
9
Q
Ureteric bud
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Collecting system (including collecting ducts)
10
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Hartnup disease
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Cant reabsorb NEUTRAL amino acids in PCT –> includes tryptophan. Tx with high protein diet + niacin
11
Q
Syndrome of apparent mineralocorticoid excess
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Hereditary deficiency in 11B-hydroxysteroid dehydrogenase –> increased cortisol (since its not being convereted into cortisone). Can acquire from glycyrrhetic acid which is present in licorice since it blocks the activity of the enzyme
12
Q
EPO release location
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Interstitial cells in peritubular capillary bed
13
Q
1,25-(OH)2D3 synthesis location
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PCT cells via 1-a-hydroxlase
14
Q
Renal oncocytoma
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Benign EPITHELIAL cell tumor w/large eosinophilic cells + abundant mitochondria, but no perinculear clearing. ddx for renal cell, similar presentation
15
Q
Thyroidization of the kidney + eosinophilic casts
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Chronic pyelonephritis
16
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Renal papillary necrosis causes
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Sickle cell (trait or disease), acute pyelo, analgesics, diabetes
17
Q
Ethacrynic acid
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Loop diuretic similar to furosemide, but can be used in patients with sulfa allergies. but be careful because can cause hyperuricemia (contraindicated in gout)
18
Q
Triameterene and amiloride
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K sparing diuretics without the benefit of alodsterone antagonism (heart failure survival)
19
Q
Aliskiren
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Direct renin inhibitor
20
Q
Pralidoxime
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AKA 2-PAM, regenerates AChE if given early
21
Q
Cold feels hot, hot feels cold + cholinergic poisoning symptoms
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Ciguatoxin (raw reef fish consumption)
22
Q
Anyphlaxis after eating dark-meat fish
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give antihistamines because the bacterial histidine decarboxylase is converting histidine to histamine so it looks like an allergy
23
Q
DNA methylation
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Occurs at CpG islands, but on cytosine and adenine residues
24
Q
Random molecular facts
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- Thiamine has a methyl - Demaminate cytosine to make uracil - Need Glycine, aspartate, glutamine to make purines (GAG)
25
Immunosupressives in de novo pyrimidine and purine synthesis
- Leflunomide inhibits dihydroorotate dehydrogenase (carbamoyl phosphate to orotic acid) - Mycophenolate and ribavirin inhibits IMP dehydrogenase (IMP to GMP) - Hydroxurea inhibits ribonucleotide reductase (UDP to dUDP) - 6MP, AZA inhibit PRPP to IMP - 5FU inhibits thymidylate synthase (dUMP to dTMP) - MTX/TMP/pyrimethamine inhibits dihydroflorate reductase (dUMP to dTMP cofactor)
26
Adenosine deaminase deficiency
Backup of ATP and dATP inhibits ribonucleotide reductase which inhibits DNA synthesis. Thus ADA deficiency (SCID) is like being born with hydroxyurea
27
Probenecid
Increases uric acid excretion in urine
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Timing of DNA repair/example of disease
Nucleotide excision repair - G1 [xeroderma picmentosum] Base excision repair - throughout cell cycle Mismatch repair - G2 [HNPCC] Nonhomologous end joining [Ataxia teleangiectasia, Fanconi anemia]
29
Osteogenesis imperfecta mechanism
Cant form triple helix pro-alpha chains in RER
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Ehlers Danlos and Menkes disease mechanism
Problems with post-exocytosis cross linking to make collage fibrils
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Ehlers Danlos types
Classic is collagen type V, vascular is collagen type III
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Menkes mechanism more specific
X-recessive. Impaired copper absorption/transport b/c of defective menkes protein --\> decreased acticity of lysyl oxidase since copper is a cofactor --\> problems with making colagen fibrils since that protein is needed for the covalent cross linking
33
Marfan mechanism
Defect in fibrillin which is scaffolding for tropoelastin (forms a sheath around elastin)
34
Shortcut rules for AD and AR
AD - defects in structural genes AR - enzyme deficiencies
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Hereditary hemorrhagic telangiectasia (aka Osler-Weber-Rendu syndrome)
Disorder of blood vessels: Telangiectasia, recurrent epistaxis, skin discolaration, AVMs, GI bleeding, hematuria [think Leigh in terms of skin and nose bleeds]
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Cystic fibrosis metabolic effects
Like taking a loop diuretic (contraction alkolosis and hypokalemia)
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Duchenne vs Becker genetics
Both XR. Frameshift vs nonframeshift (truncated/deletion vs partially functional). Deletions can cause both. Duchenne can also be duplicationsand nonsense)
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Myotonic type 1
AD. My ticker, my toupe, my testicles, my tonia
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Robertsonian translocation locations
13-15, 21-22
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Vit A
Function: Epithelial differentiation into specialized tissue, prevent squam metaplasia, treat AML (M3) and measles, visual pigment Deficiency: Night blindness, corneal degen, spots on conjunctiva, immunosupression Excess: Hepatic toxicity (guy who eats a liver and gets cirrhotic), pseudotumor cerebri
41
Vit B1 (thiamine)
Function: aTP (alpha ketogluturate, transketolase, pyruvate dehydrogenase) + branched chain ketoacid dehydrogenase Deficiency: Diagnose with RBC transketolase levels elevated. Impaired glucose breakdown.
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Vit B2 (riboflavin)
Function: FAD/FMN, redox reactions (dehydrogenase) Deficiency: Cheilosis, corneal vascularization
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Vit B3 (Niacin)
Function: NAD+, NADP+, redox reactions (dehydrogenase), derived from tryptophan and needs B2 and B6 for synthesis. Deficiency: Glossitis, pellegra Excess: Facial flushing (prostglandin excess), hyperglycemia (insulin resistance), hyperuricemia (caution in gout), hepatitis
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Vit B5 (Pantothenic acid)
Function: CoA component, fatty acid synthase Deficiency: Dermatitis, enteritis, alopecia, adrenal insufficiency --\> need for steroids and cholesterol
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Vit B6 (pyridoxal)
Function: Transamination, decarboxlayion, glycogen phosphorylase. Hella neurotransmitters (SEND GABA) Deficiency: Convulsions, hyperirritability, periphernal neuropathy, sideroblastic anemias, subderm
46
Vit B7 (Biotin)
Function: Carboxylation (1 carbon additions). PO, AM, PM Deficiency: Rare. Dermatitis, alopecia, enteritis. excessive raw egg whites or abx use.
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B12 very basic function
Methylmalonyl CoA to Succinyl CoA (which furhter goes on to make heme) Homocysteine to methionine Deficiency results in homocysteine + methylmalonic acid levels
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B6 very basic function
Succinyl CoA to Heme Homocystein to cysteine Deficiency results in homocysteine levels
49
Vit C
Function: necessary for dopamine B-hydroxylase to convert dopamine to NE. Reduce iron Deficiency: Scurvy Excess: N/V/D. Stones
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Vit E
Function: Antioxidant, protects RBC membrane from free radical damage Deficiency: Hemolytic anemia, acanthocytosis, posterior/spinocerbellar tract demylenation (resemlbes fredrieches ataxia, or B12 deficiency w/o megaloblastic anemia)
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Alcohol metabolism locations
Cytosol: EtOH --\> acetaldeyde Microsome: P450 metabolism Mitochondria: Acetaldehyde --\> Acetate
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Metabolism site shortcut
Synthesis in cytoplasm Degradation in mitochondria Both involved in urea cycle, gluconeogenesis, heme synthesis
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Arsenic's 2 actions
1) causes glycolysis to produce zero net ATP 2) Inhibits lipoic acid (a necessary component of the pyruvate dehydrogenase complex)
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ATP producing steps in glycolysis
1) PEP to Pyruvate 2) 1,3PG to 3PG
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Activators of pyruvate dehydrogenase complex
ADP, Calcium, high NAD+/NADH ratio
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Pyruvate dehydrogenase complex deficiency
Build up of pyruvate --\> neorologic defects + lactic acidosis + high serum alanine (because pyruvate gets shunted to lactate and alanine) Treat with ketogenic nutrients (lysine/leucine/high fat diet)
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What can pyruvate become? (4 things)
1) Alanine (via ALT) [B6 needs Biotin] replenish TCA or use for gluconeogenesis 4) Acetyl-CoA [B1, B2, B3, B5, Lipoic acid] If B3 involved, you'll get NADH out of it (so Lactate, and acetyl-CoA)
58
When do you get NADH in a reaction?
If B3 (Niacin) is a necessary cofactor for it
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Electronic transport chain summary
-Protons enter via: Complex I, III, IV. -Protons exit via: Complex V -NADH pairs with Complex 1 -FADH2 pairs with Complex 2 (Succinate dehydrogenase, the only enzyme that participates in both ETC and TCA) -CoQ between II and III, Cytochrome C between III and IV - Cyanide and CO block Complex IV
60
ATP equivalents for NADH/FADH via ATP synthase
NADH = 2.5 ATP FADH = 1.5 ATP
61
ETC poisonin
Oligomycin: Directly inhibits ATP synthase Aspirin: Uncoupling agent Thermogenin: Uncoupling agent in brown fat
62
Gluconeogensis and fat
Odd chain fatty acids --\> propionyl-CoA --\> can enter TCA to become glucose Even chain fatty acids --\> only yield Acetyl-CoA--\> cannot ever become glucose
63
NADPH uses
Fatty acid/cholesterol synthesis, glutathione reduction. Therefor it will be found in places that need it: lactating mammary glands, liver, adrenal cortex, sites of fatty acid or steroid synthesis, RBCs
64
Disacharides
Lactose = galactose + glucose Sucrose = fructose + glucose Maltose = glucose x 2
65
Galactokinase deficiency
Failure to develop a smile or track objects, infantile catarcts (galactitol via aldose reductase). Imagine a kid who doesn't like to drink milk.
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Classic galactosemia
Failure to thrive, cataracts, hepatomegaly. E. coli sepsis in neonates. (galactose 1 phosphate) uridyltransferase
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Tissues that have BOTH aldose reductase (glucose to sorbital) AND sorbitol dehydrogenase (sorbitol to fructose)
Liver, ovaries, seminal vesicles. Need NADPH for aldose reductase and NAD+ for sorbitol dehydrogenase
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Tissues that have only or primarily aldose reductase
Schwann cells, retina, kidneys, lens (all places that get damaged with diabetics)
69
Urea cycle
-Urea nitrogens are from NH3 and aspartate -Ordinarily, careless crappers are also frivilous about urinating
70
Transporting ammonia via alanine and glutamate (general principles)
- AA becomes an alpha-ketoacid once it donates its NH3 to an acceptor (alpha-ketogluturate) to form glutamate - Pyruvate + glutamate = Alanine - Alanine can go from muscle to liver where the NH3 is taken away to form glutamate with alpha-ketoglurate. Then glutamate can be turned into urea - Lactate returns from muscle to liver where it is converted to pyruvate, then to glucose, so it can go back
71
Hyperammonemia pathophys
Will deplete alpha-ketoglutarate thus inhibiting TCA. Tx: lactulose to acidify, rifaximin to decrease colonic ammongiagenic bacteria, benzoate/phenylbutyrate to bind AAs to excrete them. Example of cause: liver disease, N-acetylglutamate synthase deficiency
72
Ornithine transcarbamylase deficiency
XR, other urea cycle defects are AR. Body cant eliminate ammonia. Carbamoly phosphate converted to orotic acid (pyrmidine synthesis pathway) instead. no megaloblastic anemia like orotic aciduria
73
PKU
-Low phenylalanine hydroxlase OR low tetrahydrobiopterin cofactor aka BH4 (malignant PKU) -Tyrosine now is essentially since it cant be synthesized from phenylalanine - Excess phenylaline will downregulate tyrosinase which converts tyrosine to melanin --\> fair pigmented skin ALBINO Must body odor. Aspartame has phenylalanine
74
Maple syrup urine disease
Branched chain amino acids dont get degraded because of low alpha-ketoacid dehydrogenase. B1 dependent enzyme, so supplement with thiamine
75
Alkaptonuria
Tyrosine to fumurate pathway compromised because of homogentisate oxidase. Pigmented, arthralgias. Urine turnks black in air.
76
3 causes of homocysteinuria (clinical manifestations: intellectual disability, marfinoid habitus, kyphosis, thrombosis, lens subluxation)
1) B12 deficiency: necessary coenzyme for homocystein methyltransferase to make methionine (tx: methionine in diet) 2) Cystationine synthase deficiency (tx: decrease methionine since that pathway will be predominant, increase cysteine since its missing now) 3) Decreased affinity of cystationine synthase for B6 (tx: increase B6 and cysteine in diet)
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Stimulators of glycogen phosphorylase kinase (which goes on to phosphorylate glyogen phosphorylase and promote gluconeogenesis)
PKA (via glucagon and B-receptor) Calcium-calmodulin during muscle contraction Calcium directly
78
Glycogen storage disease summary
Von Gierke (T1): glucose 6 phosphate is only in liver, so hepatomegaly and a lot of glycogen in liver. High blood lactate level Pompe (T2): Lysosomal a14 glucosidase (acid maltase) defect trashing the pumps (hypertrophic cardiomyopathy, cardiomegaly, liver, muscle Cori (T3): 1,6 debrancher, gluconeogenesis is intact, mild form of Von Gierke but w/normal blood lactate level McArdle (T5): skeletal muscle gylocgen phosphorylase, so painful muscle cramps and myoglobinuria with exercise. Normal blood glucose levels. Tx with B6.
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Lysosomal storage disease high yield
Fabry disease: XR. Angiokeratomas, peripheral neuropathy. "Within the Fabric of the universe is a galaxy of skin spots" Gaucher disease: Hepatosplenomegaly. Pancytopenia. Crumpled tissue paper (lipid laden macrophages). Bone problems. "My BRO has an iPhone 3G (GlucocerBROsidase, GlucocereBROside) Niemann-Pick disease: Neurodegen. Hepatosplenomegaly. "No man picks his nose with his shpinger". Foam cells (lipid laden macrophages). Cherry-red macula Tay-SaX disease: Neurodegen. Onion skin lysosomes. NO hepatosplenomegaly. Cherry-red macula. HeXo A, GM2 gang Krabbe disease: Peripheral neuropathy, optic atrophy. glboid cells ("glob of fat" Metachromatic leukodystrophy disease: Central + peripheral demyelination w/ataxia + dementia Hurler syndrome:Gargoylism, corneal clouding, hepatosplenomegaly. Heparan sulfate, dermatan sulfate. Hunter syndrome: XR. Mild Hurler + aggressive behavior (being a hunter) w/o corneal clouding. Heparan sulfate, dermatan sulfate.
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Fatty acid metabolism
Citrate shuttle (sytrate, synthesis), occurs in cytosol Carnitine shuttle (carnage), occurs in mitochondria Systemic primary carnitine deficiency leads to toxic accumulation of fatty acids outside in cyotosol: hypoketotic hypoglycemia. Similar presentation to medium chain acyl-CoA dehydrogenase deficiency, which results in the same presentation w/minor illness or fasting.
81
Ketone bodies
Prolonged starvation --\> decrease in oxaloacetate for gluconeogenesis --\> buildup of acetyl-CoA --\> shunts glucose/FFA towards production of ketone bodies Test only picks up acetoacetate (not B-hydroxbutyrate) RBCs cant use ketones
82
Lipid metabolism
ApoE (in blood) = signal for liver takeup Apo CII (in blood) = cofactor/signal for lipoproteim lipase ApoB-48 (in lymph) = chylomicron ApoB-100 = 100% came from the liver. Also a marker for LDL uptake by tissue, binds LDL receptors. AI activates LCAT, only on chylomicron and HDL
83
RR vs OR
Relative risk reports risk of developing disease in groups with or without exposure Odds ratio is for case-control because these patients already have the disease and we are looking at how their exposure in the past correlates.
84
Platelet granules/endothelial
Dense granule = ADP, Ca2+ Alpha granule = vWF, fibrinogen Weibel-Palade bodies (endothelial cells) = vWF, P-selection Endothelial cells also have VIII
85
Basophilia
CML
86
Basophilic stippling in lead poisoning
From inhibition of rRNA degradation, aggregates of rRNA Also look for lead lines on gingivae and metaphyses of long bones Wirst and foot drop
87
Eculizumab
Terminal complement inhibitor for paroxysmal nocturnal hemoglobinuria Pronounce "eludumab" to elude the immune system
88
Corticosteroids on neutrophils and eos
Neutrophilia, but eosinopenia b/c squesters them in lymph nodes and cause apoptosis of lymphocytes
89
Enzyme defects in porphyrias
Sideroblastic: ALA synthase (B6) Lead Poisoning: ALA dehydratase, Ferrochelatase Acute intermittent porphyria: Porphobilinogen deaminase Porphyria cutanea tarda: Uroporphyrinogen decarboxylase
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Pathophys of ITP
Antibodies against GpIIb/IIIa
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Pathophys of TTP
Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease)
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Antithrombin deficiency effect on PT/PTT/bleeding time
None, could be trick question, be careful
93
Reed-Sternberg Cells
CD15+, CD30+ (think biphasic, 15 yr olds and 30 yr olds)
94
DDx for lytic bone lesion and hypercalcemia
Primary hyperparathyroidism (causes osteitis fibrosa cystica), multiple myeloma, Adult T-cell lymphoma
95
Cerebriform nuclei
Mycosis fungoides/Sezary syndrome
96
ALL
TdT+ and CD10+ if pre-B cell Can spread to testes/CNS
97
SLL/CLL
CD20+ CD5+ Smude cells Autoimmune hemolytic anemia
98
Hairy cell leukemia
TRAP+ Cells get TRAPed in red pulp, marrow fibrosis, get dry bone marrow Mature B-cells Tx with cladribine, pentostatin
99
AML
Peroxidase+ M3 has cytoplasmic inclusions Risk factors with alkylating agents, radiation, myeloproliferative disorders
100
CML
Low ALP (to contrast to leukomoid reaction) Basophilia Splenomegaly Can trasnform to AML or ALL (blast crisis) Tx with imatinib
101
Langerhans cell histiocytosis
lytic bone lesions, skin rash, reucrrent otitis media, mastoid bone mass, S100 marker, CD1a marker. Birbeck granules
102
Ticagrelor dangerous side effect
Neutropenia
103
Cilostazol, dipyridamole
Phosphodiesterase III inhibitors that increase platelet cAMP, preventing ADP receptors from functioning. Also causes vasodiltation. DUAL EFFECT.
104
Abciximab, eptifibatide, tirofiban
GpIIb/IIIa inhibitors
105
B-lactamases location
Periplasm
106
Mycolic acid is detected by what in an acid-fast stain?
Carbofuchsin
107
Stains
Giemsa - Malaria + parasites (including intracellular) Ziehl-Neelson (carbol fuchsin) - Acid-fast bacteria, protozoa India Ink or Mucicarmine - Cryptococcus Silver Stain - Fungi, legionella, H. pylori
108
Special culture requirements
Chocolate: h.flu Thayer-Martin: Neisseria (vanc, colistin, trimeth, nystatin) Regan-Lowe (+Bordet-Gengou): Bordetella Tellurie or Loffler - "Ill tell you right now, its diptheriae" Eaton agar - Mycoplasma pneumo (cholesterol) MacConkey-lactose fermenters Eosin-methylene blue - Ecoli Charcoal/cystein/iron - legionella Sabouraud: fungi
109
AminOglycocydes (streptomycin, etc) ineffective against:
aerobes, requires O2 to enter cell
Only use for severe gram (-) rod infections
110
Obligate aneorobes
Really chilly and cold: Ricketsia, chlamydia, coxiella
111
Urease positive
PUNCH-K: Pseudomonas Ureaplasma Nocardia Cryptococcus H. pylori Klebsiella
112
Catalase positive
Cats Need PLACESS: Nocardia Listeria Aspergillus Candida E.coli Staph Serratia
113
Bacterial virulence factors
Staph aureus - Protein A SHiN - IgA protease GBS - M protein
114
All exotoxins except one are destroyed at temps above 60C. What is that exotoxin?
Staphylococcal entertoxin. Also, endotoxin (gram negatives) is stable at 100C for 1hr
115
Exotoxins
- Diptheria and Pseudomonas inactivate EF-2 - Shigella and EHEC inactivate 60S ribosome by removing adenine from rRNA - ETEC has LT, ST; Vibrio cholerae has the equivalent of a LT toxin, except it PERMENTANTLY activates Gs (labile in the cAir, stabile on the cGround) - Bacillus anthracis and Bordetella have a toxin that mimics adenylate cyclase - Bordetella has a LT toxin equivalent, but does so by DISABLING Gi - Clostridium tetani and botulinum cleave SNARE - Clostridium perfringes (Alpha toxin) and Strep pyogens (ASO) degrade cell membrane - Staph aureus (TSST-1), Strep pyogenes (exotoxin A) bind MHC II/TCR --\> IL1, IL2, IFN-y, TNFa --\> shock
116
Toxins encoded by lysogenic phage
Shiga-like toxin (EHEC) Botulinum toxin Cholera Diptheria Erythrogenic toxin of GBS
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