Boards Flashcards
Bacteria with unusual cell walls
Mycoplasma - Sterols & no cell wall
Mycobacteria - Mycolic acid & high lipid content
Polypeptide capsule
B. anthracis
All other are polysaccharide
What are the spirochetes?
Borrelia
Leptospira
Treponema
Giemsa stained bugs
“Certain Bugs Really Try my Patience”
Chlamydia Borrelia Rickettsiae Trypanosomes Plasmodium
PAS Stain bugs
Stains glycogen
Tropheryma whipplei (whipple’s disease)
Zeihl-Neelsen bugs
Acid-fast organisms
Nocardia
Mycobacterium
India ink bugs
Cryptococcus neoformans
Silver stain bugs
Fungi
Legionella
H. pylori
H. flu culture requirements
Chocolate agar (Factor V & X)
Neisseria (both) culture requirements
Thayer-Martin (VPN: Vanc, Polymixin, Nystatin) media
To inhibit all others
Bordetella pertussis culture requirements
Bordet-Gengou (potato) agar
Bordet for Bordetella
Corynebacterium diphtheriae culture requirements
Tellurite Plate, Loffler’s media
Teller she’s right, laugh at her after
MTB culture requirements
Lowenstein-Jensen agar
Mycoplasma pneumoniae culture requirements
Eaton’s agar
Lactose+ enterics culture requirements
MacConkey’s agar
shows pink colonies
Legionella culture requirements
Charcoal yeast extract with cysteine & iron
Fungi culture requirements
Sabouraud’s Agar
“Sab’s a fun-guy”
Obligate aerobes
“Nagging Pests Must Breathe”
Nocardia
Pseudomonas
MTB
Bacillus
Obligate anaerobes
Clostridium
Bacteroides
Generally foul-smelling, produce gas in tissue, and resistant to amin(O2)glycosides
Obligate intracellular bacteria
Stay inside when it’s Really Cold:
Rickettsia
Chlamydia
They can’t make their own ATP.
Facultative intracellular bacteria
“Some Nasty Bugs May Live FacultativeLY”
Salmonella Neisseria Brucella Mycobacterium Listeria Francisella Legionella Yersinia pestis
Test for encapsulated bacteria
Quellung reaction (anti-capsule antisera)
If serum is added –> qapsular swellung (quellung)
Encapsulated bacteria
SHiNE SKiS
Strep pneumo H. flu Neisseria meningitidis E. coli Salmonella Klebsiella Strep B (GBS)
Catalase positive organisms
“You need PLACESS for your cats”
Pseudomonas Listeria Aspergillus Candida E. coli Staph aureus Serratia
Protein-conjugated vaccines
Prevnar (pneumococcal)
H. flu type B
Meningococcal
Urease positive organisms
K PUNCHES
Klebsiella Proteus Ureaplasma Nocardia Cryptococcus (fungi) H. pylori Epidermidis Saprophyticus
Pigment producing bacteria:
Red
Green/Blue
Yellow
Red = Serratia Green/Blue = Pseudomonas Yellow = either Actinomyces israelii or Staph aureus
IgA protease containing bacteria
SHiN
Strep pneumo
H. influenza (Type B)
Neisseria
They can all transform DNA and all have an IgA protease (to colonize respiratory epithelium)
Transforming bacteria
SHiN
Strep pneumo
H. influenza (Type B)
Neisseria
They also have IgA protease
Group A Strep virulence factor
M protein
Prevents phagocytosis
Staph aureus virulence factor
Protein A
Binds Fc region of Ig to prevent opsonization & phagocytosis
C. diphtheriae toxin
Diphtheria toxin - inactivates elongation factor (EF-2)
Pseudomonas toxin
Exotoxin A - inactivates elongation factor (EF-2)
Shigella toxin
Shiga toxin:
inactivates 60S ribosome by removing adenine from rRNA
EHEC toxin
*Includes O157:H7
Shiga-like toxin:
inactivates 60S ribosome by removing adenine from rRNA
ETEC toxin
Two toxins:
Heat-labile - ^ adenylate cyclase activity –> Cl- excretion
Heat-stable - ^ guanylate cyclase activity –> decreased NaCl absorption
“Labile in the Air, Stable on the Ground”
Anthrax toxin
Edema factor - mimics adenylate cyclase activity
Vibrio toxin
Cholera toxin:
Permanently activates Gs subunit –> ^ adenylate cyclase activity –> ^ Cl- secretion in gut
Pertussis toxin
Pertussis toxin:
Disables Gi –> ^ adenylate cyclase activity –> impaired phagocytosis
Clostridium tetani toxin
Tetanospasmin - cleaves GABA and Glycine SNARE proteins
Clostridium botulinum toxin
Botulinum toxin - Cleaves Ach SNARE proteins
Clostridium perfringens toxin
Alpha toxin/Phospholipase C/Lecithinase:
Phospholipase that degrades tissue and membranes. Causes gas gangrene and hemolysis.
Group A Strep toxin
Streptolysin O:
Degrades cell membranes –> hemolysis
What do TLR-2 and TLR-4 bind?
TLR-2 = gram+ peptidoglycan
TLR-4 = gram- LPS
Staph aureus superantigenic toxin
Toxic shock syndrome toxin 1 (TSST-1):
Connect MHCII and TCR –> activate all T cells –> ^ IFNg & IL-2
Group A Strep superantigenic toxin
Exotoxin A:
Connect MHCII and TCR –> activate all T cells –> ^ IFNg & IL-2
Bacterial toxins that are encoded in lysogenic phage
ABCDE
shigA-like toxin (EHEC) Botulinum toxin Cholera toxin Diphtheria toxin Erythrogenic toxin (GAS)
Streptococcal spp. hemolysis patterns
Alpha (partial):
Strep pneumo
Viridans strep
Beta (complete):
GAS
GBS
Gamma (absent):
Enterococcus (Group D)
Strep bovis
Novobiocin resistant/sensitive
Staph:
Saprophyticus is resistant
Epidermidis is sensitive
Streptococcus:
Optochin sensitive/resistant
Bactitracin sensitive/resistant
Optochin: Strep pneumo is afraid of-the-chin, viridans are not
Bacitracin BRAS –> B Resistant, A sensitive
Gram+ rods
Clostridium Corynebacterium Listeria Bacillus Mycobacterium
What bacterial vaccines are live-attenuated?
Only Bacille Calmette-Guerin (BCG for Tuberculosis) & F. tularensis.
Lactose fermenting enterics
test with maconCKEE’S agar
Citrobacter Klebsiella E. coli Enterobacter Serratia
Gram- rod lactose nonfermenters
Oxidase+?
Oxidase-?
Oxidase+:
Pseudomonas
H. pylori
Oxidase-:
Salmonella
Shigella
Proteus
EMB agar
Eosin-Methylene blue agar
Lactose fermenters grow as purple/black colonies. E. coli grows as a purple colony with a green shine.
Neisseria spp.
Glucose?
Maltose?
Meningococci = Maltose & glucose Gonococci = just Glucose
VDRL false positives
Viruses (mono, hepatitis)
Drugs
Rheumatic fever
Lupus & Leprosy
Rash on palms & soles DDx
Syphilis (secondary & congenital)
Rocky Mountain Spotted Fever
Coxsackie A (hand, foot, & mouth dz)
Kawasaki dz
Intestinal nematode routes of infection
Ingested - EAT
Enterobius
Ascaris
Trichinella
Cutaneous - SANd
Strongyloides
Ancylostoma
Necator
Treatment for intestinal nematodes
Bendazoles
“Roundworms are bendy”
Treatment for Cestodes & Trematodes
Cestodes (tapeworms) & Trematodes (flukes) = Praziquantel
The exceptions are those that have a cyst form: Taenia solium (cysticercosis --> bendazoles) Echinococcus granulosus (liver cysts --> bendazoles)
Which viral vaccines are live-attenuated?
Smallpox Yellow fever Chicken Pox Polio (Sabin) MMR Influenza (intranasal one)
Which viral vaccines are killed?
“RIP, eh”
Rabies
Influenza (IM)
Polio (Salk)
HAV
Which viral vaccines are recombinant?
HBV (HBsAg)
&
HPV (6, 11, 16, 18)
What are the DNA viruses?
HHAPPPPy
Hepadena Herpes Adeno Pox Parvo Papilloma Polyoma
What are the exceptions to the rule that viruses are either dsDNA or ssRNA?
ssDNA = Parvovirus (Par 1)
dsRNA = Reovirus
What viruses are associated with intussusception of the small bowl in children?
Adenovirus
&
Rotavirus
Are viruses haploid or diploid?
All are haploid except retroviruses (2 identical ssRNA copies)
Which viruses replicate in the nucleus?
The cytoplasm?
All DNA replicate in nucleus (except poxvirus)
All RNA replicate in cytoplasm (except influenza & retroviruses)
Which viruses are naked/enveloped?
“Naked CPR & PAPP
Calcivirus
Picornavirus
Reovirus
Papillomavirus
Adenovirus
Parvovirus
Polyomavirus
All others are enveloped
Which viruses are negative stranded?
“Always Bring Polymerase Or Fail Replication”
Arenavirus Bunyavirus Paramyxovirus Orthomyxovirus Filovirus Rhabdovirus
Which viruses can undergo reassortment?
Segmented genomes = BOAR
Bunyavirus
Orthomyxovirus
Arenavirus
Reovirus
C. difficile toxins
Toxin A - enterotoxin; PMN chemoattractant & secretory diarrhea
Toxin B - cytotoxin; actin depolymerization & mucosal necrosis
HIV genes, what do they encode? gag pol env rev nef
gag = p24, p7 (capsid and matrix proteins, respectively) pol = Reverse transcriptase, integrase, protease env = gp120, gp41 (gp160 is cleaved into them) rev = protein that transports viral transcripts out of nucleus nef = proteins to downregulate CD4 and MHCI
What receptor does HIV bind?
Macrophage tropic = CCR5 & CD4
T-cell tropic = CXCR4 & CD4
Early disease is macrophage tropic & late disease is T-cell tropic.
What do these indicate in the serum? HBsAg HBeAg Anti-HBs Anti-HBc Anti-HBe
HBsAg = hepatitis B infection HBeAg = active viral replication (high transmissibility) Anti-HBs = immunity to HBV Anti-HBc = window period Anti-HBe = low transmissibility
What is the order of serum markers in HBV infection?
SECES
HBsAg HBeAg Anti-HBc Anti-HBe Anti-HBs
What cohort of people are immune to HIV?
Homozygous delta32 mutation. These patients have mutant CCR5. Heterozygotes have a slower progression of HIV disease.
What dermatologic diseases can infect HIV patients?
Candida infection (thrush) Bartonella henselae (bacillary angiomatosis)
AIDS patient, GI symptoms
Cryptosporidium
What neuro diseases can infect HIV patients?
Progressive multifocal leukoencephalopathy (JC virus) Toxoplasma abscesses Cryptococcal meningitis CMV retinitis HIV dementia
What oncologic conditions are found in HIV patients?
Kaposi's Sarcoma (HHV-8) Hairy Leukoplakia (EBV) Non-Hodgkin's Lymphoma (Waldeyer's Ring) SCC (cervix or anus if MSM) CNS Lymphoma
What respiratory infections are seen in HIV patients?
Pneumocystis jirovecii
CMV pneumonia
Invasive aspergillosis
Mycobacterium avium-intracellulare (TB-like illness)
What bugs are associated with food poisoning?
Vibrio parahaemolyticus & vulnificus Bacillus cereus S. aureus Clostridium perfringens Clostridium botulinum E. coli O157:H7 Salmonella
What bugs are associated with dysentary?
Campylobacter Salmonella Shigella EHEC EIEC Yersinia enterocolitica Entamoeba histolytica
What bugs are associated with watery diarrhea?
ETEC Vibrio cholerae C. difficile (can also cause dysentery) C. perfringens Cryptosporidium (AIDS) Rotavirus (children) Norovirus (adults)
What are the common causes of pneumonia in neonates?
GBS
E. coli
What are the common causes of pneumonia in children?
“Runts May Cough Chunky Sputum”
RSV Mycoplasma Chlamydia trachomatis Chlamydia pneumoniae Strep pneumo
What are the common causes of pneumonia in young adults (18-40)?
Strep pneumo
Mycoplasma
Chlamydia pneumoniae
What are the common causes of pneumonia in older adults (40-65)?
Strep pneumo H. influenza Mycoplasma Anaerobes Viruses
What are the common causes of pneumonia in the elderly (>65)?
Step pneumo Influenza H. flu Anaerobes Gram negative rods
What are the common causes of pneumonia in nosocomial infections?
Staph
Enteric gram negative rods
What are the common causes of pneumonia in aspiration?
Anaerobes
What are the common causes of pneumonia in Alcoholics/IVDA?
Strep pneumo
Klebsiella
Staph
What are the common causes of pneumonia in CF patients?
Pseudomonas
Staph aureus
Strep pneumo
Burkholderia cepacia
What are the common causes of atypical pneumonia?
Mycoplasma
Legionella
Chlamydia
What are the common causes of meningitis in newborns (0-6 mo.)?
GBS
E. coli
Listeria
What are the common causes of meningitis in children (6m-6y)?
Strep pneumo
Neisseria meningitidis
H. flu (Type B)
Enteroviruses
What are the common causes of meningitis in most people (6-60y)?
Strep pneumo
Neisseria meningitidis (#1 in teens)
Enteroviruses
HSV
What are the common causes of meningitis in the elderly?
Strep pneumo
Gram negative rods
Listeria
What is the empiric therapy for bacterial meningitis?
Cefriaxone + Vancomycin
+ Ampicillin if < 6m or > 60y
(Listeria)
Osteomyelitis bugs: Diabetics IVDA Sickle Cell Prosthetic replacement Vertebral osteomyelitis Cat/Dog bite Everyone else
Diabetics - Pseudomonas IVDA - Pseudomonas Sickle Cell - Salmonella Prosthetic replacement - S. epidermidis Vertebral osteomyelitis - MTB Cat/Dog bite - Pasteurella multocida Everyone else - S. aureus
What does a positive nitrite test indicate?
Positive leukocyte esterase test?
Nitrite = Gram negative bacteria UTI
Leukocyte esterase = Bacterial UTI
What are the most common causes of UTI?
1) E. coli
2) Staph saprophyticus
3) Klebsiella
Others:
Proteus
Serratia (nosocomial)
Pseudomonas (nosocomial)
Enterobacter (nosocomial)
Congenital Toxoplasma presentation
Triad:
Chorioretinitis
Hydrocephalus
Intracranial calcifications
Congenital Rubella presentation
Triad: PDA Cataracts Deafness \+/- rash
Congenital CMV presentation
Convulsions (seizures)
Mute (deafness)
Violaceous rash (petechiae)
Congenital HIV presentation
Recurrent infections
Chronic diarrhea
Congenital HSV-2 presentation
Encephalitis
Herpes lesions
Congenital syphilis presentation
Stillbirth/hydrops fetalis
Syphilis facies: notched teeth, saddle nose
Saber shins
CNVIII deafness
Red rashes of childhood
Rubella (descending)
Measles (descending)
VZV (begins on trunk)
Roseola (HHV-6; follows several days high fever)
Parvovirus (slapped cheek rash)
Streptococcus pyogenes (sandpaper-like rash)
Coxsackie A (vesicular on palms, soles, oral mucosa)
What organism causes a painful genital ulcer?
Haemophilus ducreyi
“It’s so painful that you do-cry”
What is the main cause of bacterial vaginosis? What are its characteristics? Treatment?
Gardnerella vaginalis
“I don’t have a Clue why I smell Fish in the Vagina Garden”
Clue cells
Fishy smell
Gardnerella vaginalis
Treatment = Metronidazole
What is the most common bacterial STI in the United States?
Chlamydia trachomatis
What pathogen should you think of for nosocomial:
Mechanical ventilation?
Urinary catheterization?
Open wounds?
Mechanical ventilation = Pseudomonas
Urinary catheterization = E. coli, Proteus
Open wounds = S. aureus
What microbes are more common in asplenic patients?
Encapsulated organisms, especially SHiN
What is the mechanism of beta-Lactams?
Bind to PBP’s (transpeptidases) to block cross-linking of peptidoglycan.
What is the use of nafcillin?
Naf for staph
Cannot use for MRSA.
What is the spectrum of Ampicillin/Amoxicillin?
Aminopenicillins = “HELPS kill Enterococci”
H. flu E. coli Listeria Proteus Salmonella/Shigella Enterococci
What is the spectrum of Piperacillin?
Gram- rods
Group & viridans strep
Anaerobes
What are the beta-lactamase inhibitors?
Clavulonic acid
Sulbactam
Tazobactam
What is the mechanism of cephalosporins?
They are beta-lactams that inhibit cell wall synthesis
What is the spectrum of 1st generation cephalosporins?
PEcK:
gram+ cocci
Proteus
E. coli
Klebsiella
What is the spectrum of 2nd generation cephalosporins?
HEN PEcKS:
gram+ cocci H. flu Enterobacter Neisseria spp. Proteus E. coli Klebsiella Serratia
What are 3rd generation cephalosporins used for?
Ceftriaxone:
Meningitis empiric therapy
Gonorrhea
Ceftazidime/Cefoperazone:
Pseudomonas
What is the spectrum of 4th generation cephalosporins?
Everything except LAME:
Listeria
Atypicals
MRSA
Enterococci
What is the spectrum of Aztreonam?
Gram- rods only (including pseudomonas)
What is the spectrum of the Carbapenems?
Cover pretty much anything. Limited to life-threatening infections due to side effects.
“We have a positive ID on a negative MD”
Imipenem, Doripenem = gram+
Meropenem, Doripenem = gram-
What is the mechanism of Vancomycin?
Inhibits peptidoglycan formation by binding up D-ala D-ala portion of cell wall precursors.
What is the spectrum of Vancomycin?
Gram+ only
Saved for use in serious multidrug resistant organisms:
MRSA
Enterococci
C. diff
Where do each of the protein synthesis inhibitor abx work?
“Buy AT 30, CCEL at 50”
30S inhibitors:
Aminoglycosides
Tetracyclines
50S inhibitors: Chloramphenicol Clindamycin Erythromycin Linezolid
What are the common aminoglycosides?
Gentamycin Neomycin Amikacin Tobramycin Streptomycin
What is the spectrum of aminoglycosides?
Gram- rod infections
What are the toxicities of aminoglycosides?
AminO2glycosides do NNOT kill anaerobes
Nephrotoxic
Neuromuscular blockade
Ototoxic
Teratogenic
What toxicities are associated with macrolides?
MACRO:
Motility issues Arrhythmia (prolonged QT) Cholestatic hepatitis Rash eOsinophilia
What two drugs are classically used for anaerobes?
Clindamycin = anaerobes above the diaphragm Metronidazole = anaerobes below the diaphragm
What is the mechanism of Bactrim?
Bactrim = Trimethoprim-Sulfamethoxazole (TMP-SMX)
Trimethoprim - inhibits Dihydrofolate reductase
Sulfamethoxazole - inhibits Dihydropteroate synthase
What is the mechanism of Fluoroquinolones?
Inhibitis DNA Topoisomerase II (gyrase) & Topoisomerase IV
-oxacin
What is the spectrum of Fluoroquinolones?
Gram- rods of urinary and GI tracts
Neisseria
What are the clinical uses of metronidazole?
“GET GAP on the metro”
Giardia Entamoeba histolytica Trichomonas Garderella vaginalis Anaerobes Pylori (H. pylori; requires triple therapy PPI+MAC)
What is the mechanism of Metronidazole?
Forms free radicals in the bacterial cell –> cell damage & death
What distinguishes Ertapenem?
It has a longer half life (4h) but does not cover Pseudomonas.
What toxicities are associated with doxycyline?
Discoloration of teeth in children under 8y (contraindicated in pregnancy & children)
Photosensitivity
What is used for prophylaxis for MTB?
MAC?
MTB = Isoniazid MAC = Azithromycin
What is the treatment for MTB?
RIPE
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Which anti-MTB drugs are hepatotoxic?
RIP
What toxicities are found with Isoniazid?
Neurotoxic
Hepatotoxic
Drug-induced lupus
INH = Injures Neurons & Hepatocytes
What toxicities are found with Rifampin?
Hepatotoxic
Many drug interactions (^CYP450 activity)
Orange body fluids
4 R's: RNA polymerase inhibitor Revs up CYP450 Red/orange body fluids Rapid resistance if used alone
What toxicities are found with Ethambutol?
Optic side effects:
Retrobulbar neuritis
Central scotoma
Red/green color blindness
What is used as prophylaxis for gonococcal or chlamydial conjunctivitis in newborns?
Erythromycin drops
What is used as prophylaxis for pregnant women carrying GBS?
Ampicillin
What is used as prophylaxis for surgical infections?
Cefazolin (to prevent S. aureus infection)
What is used as prophylaxis for recurrent UTI’s?
TMP-SMX
What are the guidelines for prophylaxis in AIDS patients?
< 200 = TMP-SMX (PCP)
< 100 = TMP-SMX (PCP & Toxoplasmosis)
< 50 = Azithromycin (MAC)
What treatment is recommended for MRSA?
VRE?
MRSA = Vancomycin; Daptomycin; Linezolid; Tigecycline; Ceftaroline VRE = Linezolid + Streptogramins
What infections can H. influenzae cause?
haEMOPhilus
Epiglottitis
Meningitis
Otitis media
Pneumonia
Incidence has gone way down due to vaccination against Type B. Other nontypeable strains only cause mucosal infections (otitis media, conjunctivitis, bronchitis).
What do Th1 cells secrete?
gamma-Interferon
IL-2
What are the major cytokines secreted by Th2 cells?
IL-4
IL-5
IL-10
IL-13
What cytokines stimulate class switching to IgE?
IL-4 –> IgG & IgE
IL-4 + IL-13 –> IgE
What does IL-5 do?
Th2 cells
Promotes class switching to IgA and proliferation of eosinophils.
Which streptococci can be cultured in bile?
In 6.5% NaCl and bile?
Bile = both Enterococci & other Group D Strep (S. bovis)
6.5% NaCl = Just enterococci
What is the mechanism of Oseltamivir?
Oseltmivir = NA inhibitor (inhibits virion release from cells)
What are the most common pathogens in an intra-abdominal infection?
Bacteroides fragilis > E. coli > everything else (polymicrobial)
What are the clinical uses for Amphotericin B?
Pregnancy (the only antifungal) Serious systemic mycoses Cryptococcus Blasto/Histo/Coccidio Mucormycoses Invasive candida Fungal meningitis (intrathecal)
What are the adverse effects of Amphotericin B?
Fever/Chills (“Ampho-terrible”)
Hypotension
Anemia
Thrombophlebitis
What is the treatment for systemic mycoses?
Histo/Blasto/Coccidio
Itraconazole/Fluconazole for local infection
Amphotericin B for systemic infection
Cryptococcal meningitis treatment
Amphotericin B
+/- Flucytosine
What is the typical treatment for candida infection?
Fluconazole
If invasive –> Echinocandin (Caspofungin, Micafungin)
What is the mechanism of Ribavirin?
Inhibits IMP dehydrogenase –> no guanine synthesis
When is Ribavirin indicated?
RSV
Chronic Hepatitis C
When is Acyclovir indicated?
HSV and VZV infections
Does NOT work against CMV (Ganciclovir)
What are the oral forms of Acyclovir and Gancyclovir?
Valacyclovir & Valganciclovir
When is Foscarnet indicated?
CMV retinitis when Ganciclovir has failed
Acyclovir-resistant HSV
When is Cidofovir indicated?
CMV retinitis
Acyclovir-resistant HSV
What are possible regimens for HAART?
2 NRTI’s + either:
1 NNRTI
1 PI
1 Integrase inhibitor
What drug boosts other protease inhibitors in HAART?
Ritonavir
**All PI’s end in -navir
What antiretroviral is used during pregnancy?
Zidovudine (ZDV/AZT)
To reduce risk of fetal transmission.
What are the adverse effects of Protease inhibitors?
Metabolic syndrome
GI intolerance
What NRTI’s can cause lactic acidosis?
Didanosine > Stavudine > Zidovudine
What antiretroviral should be avoided in pregnancy?
Efavirenz
When is IFN-alpha indicated?
Chronic Hepatitis B & C
Kaposi’s Sarcoma
When is IFN-beta indicated?
Multiple Sclerosis
When is IFN-gamma indicated?
NADPH oxidase deficiency
Which anti-infectious agents should be avoided in pregnancy?
“SAFe Children Take Really Good Care”
Sulfonamides (Kernicterus) Aminoglycosides (Ototoxicity) Fluoroquinolones (Cartilage damage) Clarithromycin (Embryotoxic) Tetracyclines (Discolored teeth) Ribavirin (Teratogen) Griseofulvin (Teratogen) Chloramphenicol (Gray baby syndrome)
What is used to treat MAC infection?
ARES protocol:
Azithromycin
Rifampin
Ethambutol
Streptomycin
What is used to treat Hansen’s disease?
M. leprae
Long term tx
Tuberculoid form = Dapsone & Rifampin
Lepromatous form = Dapsone, Rifampin, Clofazimine
What are the respiratory fluoroquinolones?
Gemifloxacin
Levofloxacin
Moxifloxacin
What are the anti-pseudomonal fluoroquinolones?
Ciprofloxacin
Levofloxacin
Rusty colored sputum
Strep pneumo pneumonia
What are the two possible outcomes of Bacillus cereus food poisoning?
Heat stable toxin –> Emetic form (1-5h after ingestion)
Heat labile toxin –> diarrheal form (15-20h after ingestion)
What types of cells are found in a lymph node?
Where are they found?
Cortex = Follicles of B cells Paracortex = T cells (location of high endothelial venules) Medulla = Medullary cords & sinuses contain macrophages
Lymph drainage:
Upper limb
Axillary
Lymph drainage:
Breast
Axillary
Lymph drainage:
Stomach
Celiac
Lymph drainage:
Duodenum & Jejunum
Superior mesenteric
Lymph drainage:
Sigmoid colon
Colic –> inferior mesenteric
Lymph drainage:
Rectum & anus (above pectinate line)
Internal iliac
Lymph drainage: Anal canal (below pectinate line)
Superficial inguinal
Lymph drainage:
Testes
Superficial & deep plexuses –> para-aortic
Lymph drainage:
Scrotum
Superficial inguinal
Lymph drainage:
Superficial thigh
Superficial inguinal
Lymph drainage:
Dorsolateral foot
Popliteal
What are the two main lymphatic ducts and what do they drain?
Where do they empty into the circulation?
Right lymphatic duct = Right arm, Right chest, Right 1/2 of head
Thoracic duct = everything else
They both empty into their respective subclavian veins.
What infections are seen in asplenic patients?
Encapsulated organisms
Strep pneumo H. flu i Neisseria meningitidis E. coli Salmonella Klebsiella i Strep agalactiae (GBS)
What hematologic changes are seen in asplenic patients?
Howell-Jolly bodies (nuclear remnants)
Target cells
Thrombocytosis
Which way do T cells move as they mature in the thymus?
From cortex (positive selection) to medulla (negative selection).
What are the findings in Down Syndrome?
Mental retardation Flat facies Prominent epicanthal folds Oblique palpebral fissures Simian crease Gap between first 2 toes Duodenal atresia Ostium primum-type ASD (cushion defect)
What are Down syndrome patients at increased risk of?
ALL
Alzheimers (young onset)
What are the possible etiologies of Down Syndrome?
1) Meiotic nondisjunction (95% of cases; advanced maternal age)
2) Robertsonian translocation (4% of cases)
3) Mosaicism (1% of cases)
What organisms are capable of producing biofilms?
Staph epidermidis Strep mutans & sanguinis Pseudomonas Viridans strep Nontypable H. flu
What are the uses of Rifampin?
MTB & Leprosy = combination therapy
H. flu & N. meningitidis = monotherapy prophylaxis
What is Sucrose composed of?
Lactose?
Maltose?
Maltose = Glucose + Glucose Lactose = Glucose + Galactose Sucrose = Glucose + Fructose
What possible effects does uncontrolled maternal diabetes have on a fetus?
Prematurity Fetal macrosomia Neural tube defects Hypoglycemia Hypocalcemia Polycythemia NRDS Transient HOCM
What is produced through cleavage of POMC?
beta-endorphins
ACTH
MSH
What are the commonest complications of prematurity?
NRDS PDA Bronchopulmonary dysplasia Intraventricular hemorrhage (germinal matrix) Necrotizing enterocolitis Retinopathy of prematurity
What passes through the optic canal?
CNII
Ophthalmic artery
Central retinal vein
What passes through the superior orbital fissure?
CNIII, CNIV, CNV1, CNVI
Ophthalmic vein
Sympathetic fibers
What foramina do the divisions of the trigeminal nerve pass through?
Standing Room Only
V1 = Superior orbital fissure V2 = Foramen rotundum V3 = Foramen ovale
What passes through the foramen spinosum?
Middle meningeal artery & vein
What passes through the internal acoustic meatus?
CNVII, CNVIII
What passes through the jugular foramen?
CNIX, X, XI
Jugular vein
“Nine, ten, eleven, jugular foramen”
What are “Mongoloid features” associated with?
Down Syndrome
Beta-thalassemia
What HLA’s are associated with each MHC type?
MHCI = HLA-A,B,C MHCII = HLA-DR,DP,DQ
What do each MHC class bind?
MHCI –> TCR & CD8 (CTL activation)
MHCII –> TCR & CD4 (Th activation)
Where are MHCI and MHCII expressed?
MHCI = all cells except RBC's MHCII = only on APC's
What disease is this HLA subtype associated with?
A3
Hemochromatosis
What disease is this HLA subtype associated with?
B27
PAIR
Psoriasis
Ankylosing spondylitis
IBD
Reiter’s syndrome
What disease is this HLA subtype associated with?
DQ2/DQ8
“DQ2, Celiac sprue”
Also DQ8
What disease is this HLA subtype associated with?
DR2
Multiple sclerosis
Hay fever
SLE
Goodpastures
What disease is this HLA subtype associated with?
DR3
T1DM
Graves’ Disease
What disease is this HLA subtype associated with?
DR4
Rheumatoid arthritis
T1DM
What disease is this HLA subtype associated with?
DR5
Pernicious anemia
Hashimoto’s thyroiditis
What HLA’s are associated with T1DM?
DR3 & DR4
What do NK cells respond to?
Activity increased by IL-2, IL-12, IFN-alpha, IFN-beta
Activated to kill by absence of MHCI on target cell surface or nonspecific activation signals on target cell surface.
What is positive and negative selection of T cells?
Positive selection = TCR cell can bind self
Negative selection = TCR does not bind self with high affinity
These occur in the thymus.
What interactions are required for T cell activation?
CD4:
TCR/CD4-MHCII
CD28-B7 (dendritic cell)
CD8:
TCR/CD8-MHCI
CD28-B7 (dendritic cell)
What interactions are required for B cell activation?
1) BCR-mediated endocytosis
(B cell) MHCII-TCR (CD4 T cell)
(B cell) CD40-CD40L (T cell)
This causes activation of B cell & release of cytokines from T cell –> class switching, affinity maturation, Ab production
What cytokines are secreted by Th1 cells?
IFN-gamma
What cytokine induces a T cell to go the Th1 route?
IL-12
What cytokines do Th2 cells release?
IL-4, IL-5, IL-10, IL-13
What do CTL’s use to kill cells?
Perforin - holes in membrane
Granzyme - serine protease –> apoptosis inside target cell
Granulysin - induces apoptosis
What is the main purpose of a Th1 & a Th2 response?
Th1: Activates macrophages (inflammation) & intracellular immunity
Th2: Recruits eosinophils (parasites) & promotes Ig production (extracellular immunity)
What cell surface markers are found on T-regs?
CD3
CD4
CD25
What do T-regs secrete?
IL-10
TGF-beta
What are the 3 ways that Ab’s combat infection?
1) Opsonization (promotes phagocytosis)
2) Neutralization (prevents binding)
3) Complement activation (MAC)
What portion of an antibody activates complement?
CH2 portion (Fc portion close to the neck)
This only occurs with IgM & IgG
What enzyme adds additional nucleotides during V(D)J recombination?
TdT = Terminal deoxynucleotidyl Transferase
What type of Ig’s are expressed on mature B cells?
IgM & IgD
Most produced Ig subtype?
Highest serum titer?
Lowest serum titer?
Most produced = IgA
Highest titer = IgG
Lowest titer = IgE
What does IgE do?
Binds to and sensitizes mast cells & basophils
Activates eosinophils against worms
Type I hypersensitivity
What is a Thymus Independent Antigen?
Activation of B cells is T-cell independent, either by:
1) Crosslinking of BCR’s due to repeating epitopes
2) TLR activation in an innate cell –> signaling
This type of response occurs in response to non-peptide antigens, such as a polysaccharide capsule. It generates NO IMMUNOLOGIC MEMORY. This is why we have to conjugate Strep pneumo, H. flu, Neisseria vaccines to a peptide. Then there can be an immunologic memory and a thymus-dependent response.
What is the function of the membrane attack complex?
Lysis GRAM- cells by punching holes in it
What are the specific functions of the complement proteins?
C3b - opsonization
C3a, C5a - anaphylaxis
C5a - PMN chemotaxis
C5b-C9 - MAC
What are the inhibitors of complement?
Decay Accelerating Factor (DAF)
C1 Esterase Inhibitor
They help to prevent activation on self
What initiates the Classical pathway?
Alternative pathway?
Lectin pathway?
Classical = Ab bound to microbial surface Alternative = C3 spontaneously hydrolyzed to C3b Lectin = Mannose-Binding Lectin (MLB) binds mannose, glucose, etc. (polysaccharide)
How does a C1 esterase inhibitor deficiency manifest?
Hereditary angioedema, especially periorbital.
ACE inhibitors contraindicated
How does a C3 deficiency manifest?
Recurrent pyogenic sinus & respiratory tract infections
Also ^ susceptibility to Type III (immune complex) hypersensitivity because C3 is involved in clearing of immune complexes.
How do C5-C9 deficiencies manifest?
Recurrent Neisseria infections
How does DAF deficiency manifest?
Decay Accelerating Factor (GPI anchored enzyme; normally inhibits complement)
Complement mediated hemolysis & PNH
What amino acid(s) are pyrimidines synthesized from?
Glutamate + Aspartate
What amino acid(s) are purines synthesized from?
Glutamate + Aspartate + Glycine
What amino acid(s) is Niacin synthesized from?
Trpytophan
What amino acid(s) is Thyroxine synthesized from?
Tyrosine
What are the intraluminal stimuli for vasodilation?
Ach Bradykinin Serotonin Substance P Shear forces NO
What is the mechanism of Daptomycin?
Depolarization of the microbial cell membrane
What toxicity is seen with Daptomycin?
Myopathy & increased CPK
What bacteria are most commonly involved in pneumonia that is secondary to a viral infection?
In order:
1) Strep pneumo
2) Staph aureus
3) H. flu
How is mesothelioma diagnosed?
Definitive diagnosis is with EM.
Mesothelioma = long slender microvilli
Adenocarcinoma = short, plump microvilli
What is the effect of sympathetic stimulation on insulin secretion by pancreatic beta cells?
It depends:
Alpha receptor stimulation –> decreased insulin release
Beta receptor stimulation –> increased insulin release
As a whole, sympathetic stimulation generally decreases insulin release while parasympathetic stimulation increases it.
How is hemophilia inherited?
Both are usually X-linked
Hemophilia A is spontaneous in 30% of cases
How is Lesch-Nyhan Syndrome inherited?
X-linked recessive
What cancers are typically osteolytic in nature?
BLT w/ Ketchup & Mustard
Breast Lung Thyroid Kidney Multiple myeloma
What do IL-1 through IL-5 do?
Hot T-Bone stEAk
IL-1 = pyrogen IL-2 = stimulates T cells IL-3 = stimulates bone marrow IL-4 = class switch to IgE IL-5 = class switch to IgA
What does IL-6 do?
Fever & acute-phase reactants
What does IL-8 do?
The major chemoattractant for neutrophils
“Clean up on aisle 8”
What amino acid(s) is NO synthesized from?
Arginine
What cytokines are secreted by Th2 cells?
IL-4,5,10
What does IL-10 do?
Inhibits inflammation and Th1
Secreted by Th2 cells & T-regs
What occurs in cells exposed to IFN-alpha & beta?
Protein Kinase R (PKR) is produced. In the presence of dsRNA, it phosphorylates two proteins:
1) RNAse L –> degrades RNA
2) eIF2 –> inhibits translation
What cell surface markers are found on T cells?
TCR CD3 CD28 If Th - CD4, CD40L If CTL - CD8
What cell surface markers are found on B cells?
BCR (Ig)
CD19,20,21,40
MHCII
B7
What cell surface markers are found on macrophages?
CD14,40
MHCII
B7
Fc & C3b receptors (for enhanced phagocytosis)
What cell surface markers are found on NK cells?
CD16 (binds Fc of IgG)
CD56 (unique to NK)
What receptors bind LPS?
CD14 & TLR-4
macrophages
What is the half life of passive immunity?
3 weeks
What exposures require administration of passive immunity?
if you want “To Be Healed Rapidly”
Tetanus toxin
Botulinum toxin
HBV
Rabies virus
What types of responses are induced with a live-attenuated vaccine vs an inactivated one?
Live-attenuated = cellular response Killed = humoral response
Killed are safer but often requires boosters.
What does IL-12 do?
Induces differentiation of T cells into Th1 cells
Activates NK cells
What does TNF-alpha do?
Responsible for septic shock
Activates endothelium
Leukocyte recruitment
Vascular permeability
What cytokines are secreted by macrophages?
IL-1,6,8,12, TNF-alpha
When does serum sickness occur?
5-10 days post-exposure
What are serum sickness & arthus reaction?
Both are type III hypersensitivity
Serum sickness is systemic - fever, urticaria, proteinuria, LAD
Arthus reaction is localized - edema, necrosis
What are the types of blood transfusion reactions?
Allergic (Type I)
Anaphylactic
Febrile nonhemolytic transfusion reaction (FNHTR; Type II)
Acute hemolytic transfusion reaction (HTR; Type II)
Anti-dsDNA, anti-Smith
SLE
Antihistone Ab’s
Drug-induced lupus
Rheumatoid factor
anti-CCP
Rheumatoid arthritis
Anticentromere Ab’s
CREST syndrome
anti-DNA topoisomerase I
aka anti-Scl-70
Scleroderma
Anti-mitochondrial Ab’s
Primary biliary cirrhosis
IgA anti-endomysial
IgA anti-tissue transglutaminase
Celiac disease
Anti-basement membrane
Goodpasture’s
Anti-desmoglein Ab’s
Pemphigus vulgaris
Antimicrosomal
Antithyroglobulin
Hashimoto’s
Anti-Jo-1
anti-SRP
anti-Mi-2
Polymyositis/Dermatomyositis
Anti-Ro
Anti-La
aka Anti-SSA/Anti-SSB
Sjogren’s syndrome
Anti-U1 RNP
Mixed connective tissue disease
Anti-smooth muscle Ab’s
Autoimmune hepatitis
Anti-glutamate decarboxylase Ab’s
T1DM
PR3-ANCA
AKA c-ANCA
Granulomatosis with polyangiitis
MPO-ANCA
AKA p-ANCA
Microscopic polyangiitis
Churg-Strauss syndrome
What infections are seen in granulocyte deficiency?
Staphylococcus
Burkholderia cepacia
Serratia
Nocardia
Candida
Aspergillus
What infections are seen in complement deficiency?
Neisseria
What type of infections are typically seen in T vs. B cell deficiency?
T-cell deficiency = fungal & viral infections
B-cell deficiency = encapsulated bacteria, enteroviral, and giardia infection
What are the characteristics of axonal reaction?
Rounded cell body
Nucleus displaced to periphery
Central chromatolysis (dispersion of Nissl substance)
These changes are secondary to Wallerian degeneration. They represent increased protein synthesis in order to regenerate a severed axon.
What cofactors are required for:
alpha-Ketoacid Dehydrogenase
Pyruvate Dehydrogenase
alpha-Ketoglutarate Dehydrogenase
“Tender Loving Care For Nancy”
Thiamine pyrophosphate Lipoate Coenzyme A FAD NAD
What is the Ddx for pulsus paradoxis?
Pulsus paradoxis = pulses decrease with inspiration
Ddx: Cardiac tamponade Constrictive pericarditis Severe obstructive lung disease Restrictive cardiomyopathy
How do the endemic fungi appear microscopically?
Histo = small, within macrophages (Histo hides) Blasto = Blasto Buds Broadly; same size as RBC Coccidio = Large spherule filled with endospores (Coccidio crowds)
What other receptors can hCG bind to?
hCG is an LH analog & can also bind to TSH receptor if in high enough concentrations.
Thus, patients with choriocarcinoma/teratoma can exhibit hyperthyroidism and men can sometimes show gynecomastia.
What can be used to detect colon cancer recurrence?
Serume carcinoembryonic antigen (CEA)
What is seen hematalogically with CVID?
Normal number of B cells, reduced plasma cells & Ig titers
What is seen in DiGeorge syndrome?
CATCH-22
22q11 deletion syndromes: Cleft palate Abnormal facies Thymic aplasia Cardiac defects Hypocalcemia (parathyroid aplasia) 22q11 deletion
DiGeorge = TCH VeloCARDIOFACIAL = the cardiac and facial (including cleft palate) defects
What does a 22q11 deletion cause embryologically?
Malformation of:
3rd branchial pouch (inf. parathyroids & thymus)
4th branchial pouch (sup. parathyroids)
What infections are seen in IL-12 receptor deficiency?
Disseminated MTB infections
No Th1 response; no IFN-gamma
What are the symptoms of Job syndrome?
Hyper-IgE Syndrome = FATED
Facies (course) Abscesses (noninflammatory; Staph) Teeth (keep baby teeth) IgE Dermatologic problems (eczema)
What causes Job Syndrome?
Hyper-IgE Syndrome
Caused by a failure of Th1 cells to release IFN-gamma –> no neutrophil chemotaxis
What causes chronic mucocutaneous candidiasis?
Various forms of T cell dysfunction
What are the most common causes of SCID?
Severe Combine Immunodeficiency:
1) IL-2 receptor mutation (X-linked)
2) Adenosine Deaminase deficiency (ADA)
How does SCID present?
Failure to thrive
Recurrent infections (bact, viral, fungal, protozoa)
Chronic diarrhea, thrush
Absence of thymic shadow, germinal centers, and T cells
Decreased T-cell Recombinant Excision Circles (TRECs)
What is the treatment for SCID?
Bubble baby then BMT
What is the mutation seen in IgAtaxia-telangiectasia?
ATM gene mutation
Normally involved in NHEJ
What is seen in IgAtaxia-Telangiectasia?
IgA deficiency
Cerebellar defects
Spider angiomas
What serum marker is seen in IgAtaxia-telangiectasia?
^AFP
What mutation causes Hyper-IgM Syndrome?
Defective CD40L on Th cells –> B cells cannot class switch
How does Hyper-IgM syndrome present?
Sever pyogenic infections early in life
^ IgM, very low titers of all other classes
What mutation causes Wiskott-Aldrich Syndrome?
WASP gene (X-linked)
Makes T cells unable to reorganize actin cytoskeleton
What abnormal labs are seen in Wiskott-Aldrich syndrome?
Thrombocytopenia
^IgE & IgA, decreased IgM
How does Wiskott-Aldrich Syndrome present?
Wiskott-Aldrich’s TIE
Thrombocytopenic purpura
Infections
Eczema
What is mutated in Leukocyte Adhesion Deficiency?
CD18 (LFA-1 integrin on phagocytes)
What is the presentation of Leukocyte Adhesion Deficiency?
Delayed umbilical cord separation (usually caused by PMN’s)
Neutrophilia
Recurrent bacterial infections
No pus formation
What mutation causes Chediak-Higashi syndrome?
Lysosomal Trafficking Regulator gene (LYST):
Causes microtubule dysfunction in phagosome-lysosome fusion
What is seen in Chediak-Higashi Syndrome?
Recurrent staph & strep pyogenic infections Albinism Giant granules in neutrophils Peripheral neuropathy Defective primary hemostasis Neutropenia
What is defective in Chronic Granulomatous Disease?
Lack of NADPH oxidase –> no ROS –> no respiratory burst in neutrophils
What is seen in Chronic Granulomatous Disease?
Infection with catalase+ organisms (PLACESS)
Dx by either:
Dihydrorhodamine (DHR) flow cytometry
Nitroblue tetrazolium dye reduction test (no blue color –> CGD)
What causes hyperacute transplant rejection?
Preformed anti-donor Ab’s –> vessel occlusion –> ischemia/necrosis
What causes acute transplant rejection?
Is it reversible?
Recipient CTL’s reacting against donor MHC’s –> vasculitis of graft vessels with dense lymphocytic infiltrate
Reversible with immunosuppressants
What causes chronic transplant rejection?
Is it reversible?
Non-self MHCI is perceived as self MHCI with non-self antigen by recipient CTL’s –> T-cell & Ab-mediated vascular damage –> fibrosis of graft vessels & tissue
Irreversible
What organ transplants typically cause GvH disease?
Bone marrow & liver transplant
What is Hydroxychloroquine?
What toxicity is seen with it?
It’s a weak lipophilic base used to treat malaria, RA, and lupus
Can cause retinal damage or hemolysis
What is the mechanism of cyclosporine?
Binds cyclophilins –> inhibits calcineurin –> reduced production of IL-2 and IL-2R –> impaired T cell differentiation and activation
What drugs are often used as immunosuppressants in transplant recipients?
Cyclosporine Tacrolimus Sirolimus Azathioprine Muromonab-CD3 Corticosteroids
What toxicities are seen with cyclosporine?
Nephrotoxic Metabolic syndrome Tremor Gingival hyperplasia Hirsutism
What is the mechanism of Tacrolimus?
Binds FK-binding protein –> inhibits calcineurin –> decreased IL-2 secretion –> T cell suppression
What toxicities are seen with Tacrolimus?
Nephrotoxic
Metabolic syndrome
Tremor
What is the mechanism of Sirolimus (rapamycin)?
Inhibits mTOR –> T-cells unresponsive to IL-2
What toxicities are seen with Sirolimus?
Hyperlipidemia
Thrombocytopenia
Leukopenia
What is the mechanism of Azathioprine?
It’s the precursor to 6-mercaptopurine –> inhibits purine synthesis
What toxicities are seen with Azathioprine?
Bone marrow suppression
Toxic effects are increased by xanthine oxidase inhibitors (metabolized by XO normally)
What is the mechanism of Muromonab (OKT3)?
mAb against CD3 –> blocks CD3 –> no T cell activation
What toxicities are seen with Muromonab?
Cytokine release syndrome (cytokine storm)
What is recombinant G-CSF called?
GM-CSF?
rG-CSF = Filgrastim rGM-CSF = Sargrastim
What is Omalizumab used for?
Severe asthma. It is an Ab against IgE.
What measurement is determined by using a case-control study?
Cohort study?
Case control –> Odds ratio (Casino odds)
Cohort –> Relative risk
Phase I trials:
Who is enrolled?
What is the purpose?
Small number of healthy volunteers
Meant to assess safety, toxicity, pharmacokinetics
Phase II trials:
Who is enrolled?
What is the purpose?
Small number of diseased patients
Assesses efficacy, optimal dosing, and adverse effects
Phase III trials:
Who is enrolled?
What is the purpose?
Large number of diseased patients randomly assigned (RCT) to treatment of interest or standard of care/placebo.
Used to compare the new treatment to the standard of care
Phase IV trials:
Who is enrolled?
What is the purpose?
Postmarketing surveillance following FDA approval
Detects rare or long-term effects
What is the value of a sensitive test vs a specific test?
SNOUT –> Sensitive test rules out
SPIN –> Specific test rules in
What is the equation for sensitivity?
Sn = True Positive/All disease
= 1- false negative
What is the equation for PPV?
PPV = TP/(TP + FP)
What is the equation for NPV?
NPV = TN/(FN + TN)
What test descriptors vary with prevalence?
PPV –> Increases with higher prevalence (pretest probability)
NPV –> Decreases with higher prevalence (pretest probability)
Sensitivity and Specificity are fixed properties of a test.
What are the equations for incidence & prevalence?
Incidence = (# new cases over a time period)/(Population at risk)
Prevalence = (# of existing cases)/(Population at risk)
Thus Prevalence ~ (Incidence rate)*(duration of disease)
Odds ratio formula
OR = AD/BC
What is the formula for relative risk?
RR = (A/A+B)/(C/C+D)
What is the formula for Attributable Risk?
AR = (A/A+B) - (C/C+D)
What is the formula for Absolute Risk Reduction?
ARR = risk following treatment - control risk
Determines how much reduction in risk is due to a treatment.
What is the formula for number needed to treat?
NNT = 1 / Absolute Risk Reduction
What is the formula for number needed to harm?
NNH = 1 / Attributable risk
What types of error affect precision vs. accuracy?
Accuracy is affected by systematic error
Precision is affected by random error
Using only hospital inpatients as subjects.
What type of bias is this?
Berkson’s bias (a type of selection bias)
What is Hawthorne Effect?
The group knows it is being watched and changes its behavior. It’s a form of measurement bias.
“Dr. Hawthorne is watching you”
The researcher’s belief in the efficacy of a treatment changes the outcome of that treatment.
What type of bias is this?
Observer-expectancy bias
Subjects in different groups are not treated the same.
What type of bias is this?
Procedure bias
What can be done to avoid confounding bias?
Crossover studies
Goo matching of groups
Earlier detection by a new diagnostic test appears as increased survival.
What type of bias is this?
Lead-time bias
Information gathered at wrong time (i.e. after half of the patients are dead)
What kind of bias is this
Late-look bias
What % is contained in +/-1 Standard Deviation?
2?
3?
For a Gaussian distribution:
1 SD = 68%
2 SD = 95%
3 SD = 99.7%
What is the formula for for Standard Error of the Mean?
SEM = SD/(square root of n)
What is Type I & Type II error?
Type I error:
Seeing something there when it’s not (alpha accepts alternate)
alpha is the probability of making Type I error
We set significance at 0.05 to account for alpha error
Type II error:
Missing a difference that does actually exist
beta is the probability of Type II error (beta blind to difference)
What is statistical power?
The probability of correctly rejecting the null hypothesis when there is a difference. ***Increases with larger sample (there is power in numbers)
Power = 1 - beta
“Alpha accepts, Beta blinds, Power perceives”
What is Z for a 95% confidence interval?
99%?
95% CI –> Z = 1.96
99% CI –> Z = 2.58
What is the formula for confidence intervals?
It’s a range from:
[mean - Z(SEM)] to [mean + Z(SEM)]
What does Pearson’s correlation coefficient indicate?
Ranges from -1 to +1
Closer that it is to either -1 or +1 –> stronger the linear correlation of 2 variables
What is primary, secondary, and tertiary disease prevention?
Primary prevents
Secondary screens
Tertiary treats
With minors, when is parental consent not required?
Drugs, sex, and emergencies
What is assessed in Apgar scores?
Appearance, Pulse, Grimace, Activity, Respiration
Assessed at 1 minute & 5 minutes.
>7 = good
>3 = assist and stimulate
3 or less = resuscitate
What is the cutoff for low birth weight?
Less than 2500g
When should children walk & talk?
Be potty trained?
Walk/talk at 1
200 words and 2 word phrases at 2
Pee at 3 (toilet training)
What are the sleep stages and associated waveforms?
EEG waveforms: “at night BATS Drink Blood”
Awake (eyes open) = Beta Awake (eyes closed) = Alpha Stage N1 = Theta Stage N2 = Sleep spindles & K complexes Stage N3 = Delta REM = Beta
Most of time spent in N2. Sleepwalking, night terrors, bedwetting is in N3.
How often does a REM cycle occur?
What is the predominant neurotransmitter?
REM occurs every 90 minutes
ACh –> REM
NE –> inhibits REM
How does the suprachiasmatic nucleus regulate melatonin release?
SCN –> NE release –> Pineal gland –> Melatonin release
SCN is regulated by the environment (light)
What bases can be methylated?
Cytosine and Adenine
What amino acid may be methylated in histones?
Acetylated?
Methylation occurs at lysines & arginines –> histone more + –> heterochromatin
Acetylation occurs at lysines –> euchromatin –> histone less + –> euchromatin
What base pairing is the strongest?
G-C = 3 H-bonds A-T = 2 H-bonds
What is the mechanism of Hydroxyurea?
Inhibits Ribonucleotide Reductase:
UDP cannot –> dUDP
Ultimately deprives cell of Thymidine
What is the mechanism of 5-Fluorouracil?
Inhibits Thymidylate Synthase (FU, TS):
No dUMP –> dTMP
Ultimately deprives cell of Thymidine (purine)
What are the Dihydrofolate Reductase inhibitors?
Methotrexate
Trimethoprim (bacterial DHFR)
Decrease availability of THF.
N5,N10 THF required for dUMP –> dTMP (via thymidylate synthase)
What is the mechanism of 6-mercaptopurine?
Inhibits PRPP Amidotransferase (first step in dedicated purine synthesis)
It is activated by HGPRT.
Azathioprine is its prodrug.
What are the symptoms of orotic aciduria?
Megaloblastic anemia (not responsive to folate/B12) Orotic acid in the urine
What is the treatment for orotic aciduria?
Oral uridine supplementation
What does Adenosine Deaminase catalyze?
Adenosine –> Inosine
This is part of the purine salvage pathway:
Adenine –> AMP –> Adenosine –> Inosine –> Hypoxanthine –> IMP
How does ADA deficiency cause SCID?
1) Excess dATP feedback inhibits ribonucleotide reductase –> imbalance of nucleotide pool –> impaired DNA synthesis –> lymphocyte depletion
2) Toxic metabolites build up in lymphocytes
What defect is seen in Lesch-Nyhan Syndrome?
HGPRT deficiency. Normally it catalyzes:
Hypoxanthine –> IMP
Guanine –> GMP
What are the symptoms of Lesch-Nyhan Syndrome?
Mental retardation
Self-mutilation
Agression
Hyperuricemia/gout
What are the common X-linked recessive disorders?
GOLD FOB Holds His Watch
G6PD deficiency OTC deficiency Lesch-Nyhan Duchenne's (& Becker's) muscular dystrophy Fabry's disease Ocular albinism Bruton's agammaglobulinemia Hemophilia A & B Hunter's syndrome Wiskott-Aldrich syndrome
What is seen in Purine Nucleoside Phosphorylase deficiency?
T cells are killed by buildup of dGTP (vs ADA deficiency which kills both B & T cells)
Normal reactions:
Guanosine –> Hypoxanthine
Inosine –> Hypoxanthine
What are the types of mutations?
Silent –> same amino acid
Missense –> different amino acid (conservative if similar AA)
Nonsense –> early stop codon (UGA, UAA, UAG)
Frameshift –> usually truncated & nonfunctional
What is the purpose of Nucleotide Excision repair?
Removes pyrimidine dimers & 6-4 photoproducts
bulky lesions that distort helix
What disease is caused by mutated nucleotide excision repair?
Xeroderma pigmentosum
What is the sequence in Base Excision Repair?
Glycosylases recognize damaged base –> create apurinic/apyrimidinic site –> endonuclease cuts 3’ end –> lyase cuts 5’ end –> DNAP-beta fills it in –> ligase seals it
What is Base Excision Repair used for?
Removes damaged bases: Deamination products (via nitrates or spontaneous)
What disease is associated with a mutation in Miscmatch Repair?
HNPCC
MLH1 = MutL MSH2 = MutS
**They find a mismatch, then find the nearest nick and recruit an endonuclease to degrade from the nick all the way to the mismatch and it is all replaced
What do the different RNAP synthesize?
RNAP I –> rRNA
RNAP II –> mRNA
RNAP III –> tRNA
rampant, massive, tiny
What are the mRNA start and stop codons?
Start = AUG (met or f-met; inAUGural codon) Stop = UGA, UAA, UAG (U Go Away, U Are Away, U Are Gone)
How are “death cap mushrooms” toxic?
They contain alpha-amanitin –> hepatotoxic via inhibition of RNAP II
What is the signal for polyadenylation?
AAUAAA
How does anticodon sense relate to the codon?
An anticodon is reversed and complementary
Where do amino acids bind to the tRNA?
3’ CCA
What ribosomes pertain to eukaryotes vs prokaryotes?
Eukaryotes = 40S + 60S --> 80S Prokaryotes = 30S + 50S --> 70S
What cell types are permanent cells?
Neurons
skeletal muscle
cardiac muscle
What cell types are stable (quiescent) cells?
Hepatocytes
Lymphocytes
Can be stimulated to enter G1 but normally reside in G0
What cell types are labile cells?
Bone marrow Gut epithelium Skin Hair follicles Germ cells
What signals proteins to traffic to lysosomes from the golgi?
Mannose-6-Phosphate
What causes I-cell disease?
Cells cannot add Mann-6-P to proteins intended for lysosomes. Instead the proteins are secreted into the plasma.
What is seen in I-cell disease?
Course facial features
Clouded corneas
Restricted joints
High plasma levels of lysosomal enzymes
What are the various vesicular trafficking proteins and their purposed?
COPI = golgi –> ER (retrograde)
COPII = ER –> goldi (anterograde
Clathrin = trans-golgi –> lysosomes; PM –> endosomes
(responsible for receptor-mediated endocytosis)
What are the functions of the peroxisome?
Catabolism of very long chain fatty acids (beta oxidation)
Catabolism of amino acids
What is the cause of Kartagener’s Syndrome?
Dynein arm defect –> cilia dysfunction
What is seen in Kartagener’s Syndrome?
Infertility (females have some but reduced)
Bronchiectasis
Recurrent sinusitis
Often associated with situs inversus
What is Vimentin a stain for?
Connective tissue intermediate filaments
What is GFAP a stain for?
Neuroglial intermediate filaments
What is exchanged by the Na+/K+ ATPase?
Each ATP:
3 Na+ out
2 K+ in
What are the types of collagen & their location?
Type I = bONE, skin, tendon (90% of total)
Type II = car-two-lage
Type III = Reticulin (skin, blood vessels, uterus, fetal tissue)
Type IV = Basement membrane (Type IV is the floor)
What causes osteogenesis imperfecta?
Autosomal dominant deficiency in Type I collagen
What is seen in Osteogenesis Imperfecta?
Multiple easy fractures
Blue sclerae (choroidal veins seen through them)
Early hearing loss
Dental problems
What is seen in Ehlers-Danlos syndrome?
Hyperextensible skin
Hypermobile joints
Easy bruising
Associated with joint dislocation, berry aneurysms, aortic dissection
Caused by faulty COLLAGEN synthesis (vs. fibrillin for Marfan’s)
What is seen in Alport syndrome?
Split renal basement membrane –> hereditary nephritis
Deafness
Ocular disturbances
Due to abnormal Type IV collagen
What inhibits elastase?
alpha-1-Antitrypsin (A1AT)
What is the difference between direct & indirect ELISA?
Direct = tests for an Antigen in a patient’s blood
Indirect = tests for an Antibody in the patients blood
What is the Cre-lox system used for?
Targeted recombination or deletion of genes. Can be controlled by outside stimuli and targeted to cell types, etc. Useful if a global knockout mouse would die in-utero, etc.
What is variable expressivity?
Phenotype varies among individuals with the same genotype (i.e. 2 NF1 pts have varying severity)
What is pleiotropy?
One gene contributes to multiple (often seemingly unrelated) effects
What is loss of heteroygosity?
The two-hit hypothesis of tumor suppressor genes
What is linkage disequilibrium?
When 2 alleles occur together more often in a population that would be expected by chance
What is locus heterogeneity?
Mutations at different loci can produce the same phenotype
What is heteroplasmy?
Presence of both normal and mutated mitochondrial DNA –> variable expression of mitochondrial inherited disease
What is uniparental disomy?
Offspring gets 2 copies of a chromosome from 1 parent
Heterodisomy = meiosis 1 error Isodisomy = meiosis 2 error
Consider if a patient has an aut. recessive disease but only 1 parent is a carrier
What are the equations for Hardy-Weinberg?
p^2 + 2pq + q^2 = 1
and
p + q = 1
Also 2pq = carrier frequency
What is the genetic basis for Prader-Willi & Angelman’s Syndromes?
Prader-Willi: The deleted allele comes from the father or uniparental disomy of the maternal (imprinted) chromosome.
Angelman’s: The deleted allele comes from the mother or uniparental disomy of the paternal (imprinted) chromosome.
They are the same genetic deletion (15q11-15) but are normally imprinted differently based on which parent they came from. This causes differing symptoms.
What is seen in Prader-Willi syndrome?
Mental retardation
Hyperphagia/obesity
Hypogonadism
Hypotonia
What is seen in Angelman’s syndrome?
Mental retardation
Inappropriate laughter
Seizures
Ataxia
What is the pattern of X-linked recessive transmission on a pedigree?
Sons of carrier mothers have a 50% chance of showing disease.
How does an X-linked dominant disorder present on pedigree?
If mother carries the allele: 50% chance of all offspring getting it
If father carries the allele: all daughters & no sons get it
What disorder is X-linked dominant?
Hypophosphatemic Rickets:
phosphate wasting at the proximal tubule –> rickets-like presentation that is resistant to Vit. D supplementation
What diseases are inherited via mitochondria?
Mitochondrial myopathies:
Present with myopathy & CNS disease
“Ragged red fibers” on muscle biopsy
All children of affected mothers will be affected (heteroplasmy seen)
What is seen in Familial hypercholesterolemia?
Hyperlipidemia Type IIa: Autosomal dominant inheritance Homozygotes LDL = 700+ CVD early in life (often MI before 20) Tendon xanthomas
Heterozygotes LDL ~300
What is seen in Osler-Weber-Rendu syndrome?
(aka) Hereditary Hemorrhagic Telangiectasia:
Autosomal dominant inheritance Telangiectasia Recurrent epistaxis Skin discolorations AVM's
What chromosome is the huntingtin gene found on?
CAG repeats on chromosome 4
“Hunting 4 CAG’s
What is seen in Marfan’s syndrome?
Autosomal dominant fibrillin defect Affects skeleton, heart, eyes: Marfanoid habitus Hyperflexible joints Arachnodactyly Pectus excavatum Cystic medial necrosis of aorta --> aortic regurgitation & aortic dissection Mitral valve prolapse Subluxation of lens (ectopia lentis)
What chromosome is NF1 on?
Chromosome 17
von Recklinghausen = 17 letters
What is seen in Neurofibromatosis type 2?
What chromosome carries the NF2 gene?
Bilateral acoustic shwannomas
juvenile cataracts
On chromosome 22.
Type 2, NF2 –> 22
What is the most common mutation in cystic fibrosis?
Deletion of Phe508
All CF stems from mutation of CFTR gene on chromosome 7
What is seen in cystic fibrosis?
Recurrent pneumonia (S. aureus, H. flu, & Pseudomonas)
Pancreatic insuficiency (malabsorption & steatorrhea)
Meconium ileus in newborns
Bronchiectasis, chronic bronchitis
Male infertility (absence of vas deferens)
Cirrhosis (late)
Nasal polyps
Salty sweat
What is the pathogenesis of cystic fibrosis?
CFTR channel misfolded & degraded before getting to cell surface
CFTR normally:
- Secretes Cl- in lung, small intestine, & pancreas
- Reabsorbs Cl- from sweat
What causes Duchenne’s muscular dystrophy?
X-linked frameshift mutation –> deletion of dystrophin gene
Accelerated muscle breakdown is seen
What is seen in Duchenne’s muscular dystrophy?
How is the diagnosis made?
Weakness beginning with pelvic girdle muscles (Progresses superiorly) Use of Gowers' maneuver Calf pseudohypertrophy Onset before 5y
Dx: ^ CPK & muscle biopsy
What is seen in Fragile X syndrome?
X-tra large testes, ears, jaw
Autism
Mitral valve prolapse
What causes Fragile X syndrome?
^CGG repeats in FMR1 gene
It is X-linked & can be found in females but rarer
What is seen with fragile X premutation?
Females –> premature ovarian failure
Males –> tremor-ataxia in 40’s-50’s
What is seen in myotonic dystrophy?
Inability to release volitional contraction (aka unable to release handshake)
Progressive weakness
What are the trinucleotide repeat disorders?
“Try Hunting for My Fried Eggs”
Trinucleotide disorders: Huntington's (CAG) Myotonic dystrophy (CTG) Friedrich's ataxia (GAA) Fragile X (CGG)
What is capable of inducing ARDS?
Trauma Sepsis Shock Aspiration Uremia DIC Hypersensitivity reactions Acute pancreatitis Amniotic fluid embolism
Rank the conduction speed of the various cardiac tissues
His-Purkinje > Atria > Ventricles > AV node
What disease are Auer rods seen in?
Acute promyelocytic leukemia (M3)
t(15;17)
“Hey (A)! 15 miles per Auer”
What occurs following ligand binding to a tyrosine kinase receptor?
Dimerization –> Cross-phosphorylation –> Intracellular active sites exposed –> phosphorylation of tyrosine residues on target proteins
What malignancies are seen with a germline mutated Rb gene?
Retinoblastoma
Osteosarcoma
*Requires knockout of other copy (2 hit hypothesis/loss of heterozygosity)
What are the mediators of the early-phase of an asthma attack?
Histamine
Leukotrienes C4, D4, E4
What is seen in Albright’s Hereditary Osteodystrophy?
(aka) Pseudohypoparathyroidism:
Autosomal dominant kidney unresponsiveness to PTH
Symptoms:
Hypocalcemia
Short 4th/5th digits (knuckle, knuckle, dimple, dimple)
Short stature
What is allelic heterogeneity?
Different mutations at the same locus cause similar variant phenotypes
What is seen in hemochromatosis?
"Bronze diabetes" Hepatomegaly --> Cirrhosis Diabetes Skin hyperpigmentation Testicular atrophy CHF ^ risk of hepatocellular carcinoma
What is the mutation in achondroplasia?
Activating mutation of FGFR-3
chromosome 4
What type of signal sequence targets an mRNA to be translated bound to the ER?
Hydrophobic N-terminal signal sequences are recognized by signal recognition particles, which halt translation and carry the ribosome over to the RER to continue translation.
What are the CYP450 inhibitors?
MAGIC RACKS in GQ
Macrolides Amiodarone Grapefruit juice Isoniazid Cimetidine Ritonavir Acute alcohol Ciprofloxacin Ketoconazole Sulfonamides Gemfibrozil Quinidine
What are the CYP450 inducers?
“Carbemazepine By Pill Really Speeds Cyp450 Metabolism Greatly”
Carbemazipine Barbiturates Phenytoin Rifampin St. John's Wort Chronic alcohol Modafinil Griseofulvin
What part of the bone is generally affected in osteomalacia?
Unmineralized osteoid matrix surrounding the normally mineralized trabeculae
What causes Li-Fraumeni syndrome?
What is seen?
Germline p53 mutation
2nd hit causes:
Early onset breast cancer
Soft tissue sarcomas
Where do the recurrent laryngeal nerves loop around?
R. side loops around the R. subclavian
L. side loops around the aortic arch
Are efferent nerves myelinated or unmyelinated?
All are myelinated except for postganglionic autonomic neurons
Are afferent nerves myelinated or unmyelinated?
They are myelinated, with the exception of slow C fibers (heat & pain from free nerve endings).
What is the most common cause of aseptic meningitis?
Enteroviruses
poliovirus, coxsackie, echovirus, HepA
What occupies MHC molecules during their synthesis & processing?
MHCI –> beta-2-microglobulin
MHCII –> invariant chain
Who commonly gets molluscum contagiosum?
Children, sexually active adults, & immunodeficiency patients.
It is a poxvirus
What is seen in the first trimester pregnancy screen for:
Down syndrome?
Edwards’ syndrome?
Order goes alpha-fetoprotein, beta-hCG, estriol, inhibin-A
Down: down-up-down-up
Edwards: down-down-down-normal
What is seen on the FIRST-trimester pregnancy screen for Patau syndrome?
Decreased hCG
Decreased PAPP-A
Nuchal translucency
What is seen in Edwards’ syndrome?
Trisomy 18: Severe mental retardation Rocker-bottom feet Low set ears Micrognothia (small jaw) Prominent occiput Clenched hands Congenital heart disease
Death usually occurs in <1y
What is seen in Patau syndrome?
Trisomy 13: Severe mental retardation Cleft lip/palate Microcephaly Holoprosencephaly Polydactyly Congenital heart disease
Death occurs in <1y
Rocker-bottom feet
What chromosomes are at risk for Robertsonian translocations?
13, 14, 15, 21, 22
They are acrocentric chromosomes (1 large q arm and a tiny p arm) –> q arm is duplicated & p arm is lost –> normal if balanced, deletions/duplications if unbalanced
What causes cri-du-chat syndrome?
What is seen?
Microdeletion on 5p (short arm)
Symptoms: Mental retardation Crying/meowing (Cri-du-chat = cry of the cat) Epicanthal folds VSD Microcephaly
What causes Williams syndrome?
What is seen?
Microdeletion on long arm of chromosome 7
Symptoms: Elfin facies Intellectual disability Vit. D sensitivity --> Hypercalcemia Extreme friendliness with strangers Cardiovascular problems (elastin is deleted)
What is seen in Reiter’s syndrome?
aka Reactive arthritis Triad of: Conjunctivitis Urethritis Seronegative arthritis "Can't see, can't pee, can't climb a tree"
Associated with GU infection by: Chlamydia, Campylobacter, Salmonella, Shigella, or Yersinia
HLA-B27
How does dermatitis herpetiformis present?
What is the cause?
Presents as pruritic lesions on the extensor surfaces
Celiac sprue –> IgA/IgG cross-react with reticulin in dermal papillary tips
What conditions are associated with acanthosis nigricans?
Insulin resistance
GI or lung malignancy
Where is eukaryotic DNA methylated?
Why?
At CpG islands. This causes genetic silencing of this region & is associated with imprinting, etc.
What sinuses are most commonly affected by URI?
Maxillary sinuses
Because their drainage is superior, so gravity doesn’t favor it.
What cancers can show mets to the left supraclavicular node?
Virchow’s node drains the thoracic duct. Abdominal (GI) malignancies typically can show lymphatic dissemination to Virchow’s node.
What lung pathogen is associated with blood clots?
Aspergillus
What does retinol do?
Antioxidant
Constituent of visual pigments (retinal)
Differentiates epithelial cells (ATRA for APL)
Prevents SCC
What is seen in retinol deficiency?
Vitamin A deficiency –> Night blindness & dry skin
What is seen with hypervitaminosis A?
Teratogenic (cleft palate, cardiac abnormalities) Arthralgias Headache (cerebral edema) Alopecia Sore throat
What is B1 used for?
Thiamine --> TPP Used for decarboxylation reactions: Pyruvate dehydrogenase alpha-ketoglutarate dehydrogenase Transketolase Branched-chain amino acid dehydrogenase
What is seen in Thiamine deficiency?
1) Wernicke-Korsakoff syndrome - eyes, lies, capsize
2) Dry Ber1Ber1 - polyneuritis, symmetrical muscle wasting
3) Wet Ber1Ber1 - dilated cardiomyopathy, edema
What should be administered to an alcoholic with low glucose?
B1 FIRST, then glucose.
Giving glucose in the setting of thiamine deficiency can worsen symptoms.
What is Vitamin B3 used for?
Niacin - part of NAD+ & NADP+ (B3 –> 3 ATP)
Synthesized from tryptophan & requires B6
What is seen with B3 deficiency?
Excess?
Niacin deficiency –> Pellegra
Pellegra (3 D’s):
Diarrhea
Dermatitis (Casal’s necklace)
Dementia
Excess –> facial flushing
What can result in B3 deficiency?
Niacin deficiency can result from: Hartnup disease Carcinoid syndrome (^ tryptophan metabolism) INH (can cause B6 deficiency)
What is Vit. B2 used for?
Riboflavin –> FAD & FMN (B2 –> 2 ATP)
What is seen in B2 deficiency?
Riboflavin deficiency (2 C’s):
Cheilosis (inflamed lips, fissures at the corners)
Corneal vascularizaiton
What is Vit. B5 used for?
Pantothenate - a component of CoA & fatty acid synthase
“Pentothenate” = B5
What is seen with B5 deficiency?
Pantothenate deficiency: Dermatitis Adrenal insufficiency Enteritis Alopecia
What is Vit. B6 used for?
Pyridoxine - converted to pyridoxal phosphate
Used in:
Transamination (ALT/AST)
Decarboxylation
Glycogen phosphorylase
Synthesis of cystathionine, heme, niacin, histamine, serotonin, epinephrine, NE, GABA
What are the common causes of B6 deficiency?
What is seen?
Pyridoxine deficiency caused by - INH & OCP use Symptoms: Convulsions Hyper-irritability Peripheral neuropathy Sideroblastic anemia
What is Vit. B7 used for?
Biotin - cofactor for carboxylation enzymes:
Pyruvate carboxylase
Acetyl-CoA carboxylase
Propionyl-CoA carboxylase
What is seen in B7 deficiency?
Biotin deficiency is rare (abx use or egg white over-ingestion) Symptoms: Dermatitis Enteritis Alopecia
What is the Vit. B9 used for?
Folic acid - converted to THF for methylation rxns in DNA/RNA synthesis
Found in leafy green vegetables
What is seen in Vit. B9 deficiency?
Folic acid deficiency - seen in pregnancy & alcoholism
Megaloblastic anemia
Neural tube defects in pregnancy
*Most common vitamin deficiency in the U.S.
What is B12 used for?
Cobalamin used for: Homocysteine methyltransferase (Homocysteine --> Methionine; also regenerates THF for thymidylate synthase)
Methylmalonyl-CoA mutase (Methylmalonyl-CoA (from odd-chain FA’s) –> Succinyl-CoA)
What is seen in B12 deficiency?
What causes it?
Cobalamin deficiency:
Megaloblastic anemia
Hypersegmented PMN’s
Subacute combined degeneration (abnormal myelin)
Caused by:
Malabsorption
Diphyllabothrium latum
Lack of IF (pernicious anemia, gastric bypass)
Lack of terminal ileum (Crohn’s)
Alcoholics
Use Schilling test (radiolabeled B12) to determine cause
What is S-adenosyl methionine used for?
SAM (ATP + methionine) is used for conversion of NE –> EPI
Requires Folic acid & B12 to regenerate Methionine (& thus SAM)
What is Vit. C used for?
Ascorbic acid:
Antioxidant
Aids in Fe2+ absorption
Hydroxylation of proline & lysine in collagen synthesis
Used in dopamine beta-hydroxylase (Dop –> NE)
What is seen in Vit. C deficiency?
Scurvy: Swollen gums Bruising Hemarthrosis Anemia Poor wound healing Weakened immune response
What is seen with Vit. C excess?
N/V
Diarrhea
Fatigue
Iron toxicity
What are the forms of Vit. D and their uses?
D2 - ergocalciferol; ingested form plants
D3 - cholecalciferol; ingested in milk & synthesized in skin
25-OH-D3 - storage form
1,25-OH-D3 - Calcitriol; active form
What is the function of Vit. E?
What is seen in deficiency?
Antioxidant for erythrocytes
Deficiency –> hemolytic anemia & subacute combined degeration
What is the use of Vit. K?
K is for Koagulation
Catalyzes gamma-carboxylation of glutamic acid residues on clotting proteins (II, VII, IX, X, C, S)
What is seen in Vit. K deficiency?
Hemorrhagic disease of the newborn (given shot @ birth)
^ PT & aPTT but normal bleeding time
Can also be seen following prolonged use of broad-spectrum antibiotics (only acquired through intestinal flora synthesis)
What is seen in Zn deficiency?
Delayed wound healing
Hypogonadism
Anosmia/Dysgeusia
What is Fomepizole used for?
Fomepizole inhibits alcohol dehydrogenase - it is the antidote for methanol or ethylene glycol poisoning.
How does ethanol cause hypoglycemia?
It increases the NADH/NAD+ ratio in the liver –> inhibition of gluconeogenesis & ^ fatty acid synthesis (fatty liver).
What is Kwashiorkor?
Marasmus?
Kwashiorkor - lack of protein –> skin lesions, edema, fatty liver, anemia, protruberant abdomen, change in hair color
Marasmus - lack of calories –> loss of subQ fat, loss of muscle, edema
What is the net ATP production by 1 molecule of glucose?
Aerobic (muscle; glycerol-3-P shuttle) - 30 ATP
Aerobic (heart/liver; malate-aspartate shuttle) - 32 ATP
Anaerobic glycolysis - 2 ATP
How are hexokinase & glucokinase different?
Hexokinase - ubiquitous, high affinity, low Vmax, inhibited by Glu-6-P
Glucokinase - liver & pancreatic beta cells, low affinity, high Vmax, inhibited by Fru-6-P
So at low [glu], sequestration in the tissues, and at high [glu], sequestration in the liver.
What is the net equation for glycolysis?
Glu + 2ADP + 2NAD+ –> 2pyruvate + 2ATP + 2NADH + 2H+ + 2H20
How do hormones affect Fructose-2,6-Bisphosphate levels?
Glucagon –> ^ cAMP –> ^ PKA –> phosphorylates to activate Fructose-2,6-Bisphosphatase –> less Fructose-2,6-BP –> inhibited PFK-1 –> inhibited glycolysis
Insulin does the opposite, by decreasing cAMP –> eventual ^ in PFK-2 activity –> ^ Fru-2,6-BP –> ^ PFK-1 activity –> glycolysis
How does arsenic act as a poison?
What are the symptoms?
Arsenic inhibits lipoic acid –> inhibited functioning of pyruvate dehydrogenase
Symptoms:
Vomiting
Rice water stools
Garlic breath
What is the antidote to arsenic poisoning?
Dimercaprol
It competes with pyruvate dehydrogenase thiols and binds up arsenic, which can then be excreted in the urine.
What is the treatment for pyruvate dehydrogenase complex deficiency?
Most mutations are X-linked –> neurologic defects from birth
Treatment = ketogenic diet (fats, Lysine & Leucine)
What is the rate-limiting step in glycolysis?
How is it regulated?
Fructose-6-P –> Fructose-1,6-Bisphosphate
(PFK-1)
PFK-1 ^ by AMP & Fructose-2,6-Bisphosphate
PFK-1 inhibited by ATP & Citrate
What steps in glycolysis require ATP?
Glucose –> Glucose-6-Phosphate
(Hexokinase/Glucokinase)
Fructose-6-Phosphate –> Fructose-1,6-Bisphosphate
(PFK-1)
What steps in glycolysis liberate ATP?
1,3-Bisphosphoglycerate –> 3-Phosphoglycerate (2 ATP total)
(Phosphoglycerate kinase)
Phosphoenolpyruvate –> Pyruvate (2 ATP total)
(Pyruvate kinase)
What are the possible fates of Pyruvate produced by glycolysis?
1) Pyruvate –> Alanine
(ALT; Used to carry NH3 to the liver via the Alanine cycle)
2) Pyruvate + Co2 + ATP –> Oxaloacetate
(Pyruvate carboxylase; Produces Oxaloacetate to replenish it in the TCA cycle or for gluconeogenesis)
3) Pyruvate –> Acetyl-CoA + NADH + CO2
(Pyruvate dehydrogenase; Transition from glycolysis to TCA cycle)
4) Pyruvate –> Lactate + NAD+
(LDH; The end of anaerobic glycolysis, regenerates NAD+; Lactate enters Cori cycle)
What tissues undergo anaerobic glycolysis as their major pathway?
RBC's Leukocytes Kidney medulla Lens Cornea Testes
What is produced by the TCA cycle?
Per 1 Acetyl-CoA: 3 NADH 1 FADH2 2 CO2 1 GTP
So 10 ATP total per Acetyl-CoA (x2 per glucose)
What are the intermediates of the TCA cycle?
Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate
Citrate Isocitrate alpha-Ketoglutarate Succinyl-CoA Succinate Fumarate Malate Oxaloacetate
What is cortisol’s effect regarding vascular & bronchial smooth muscle?
Cortisol is permissive because it increases vascular & bronchial smooth muscle reactivity to catecholamines.
How can you identify the class of antiretroviral drug?
-navir = protease inhibitor Raltegravir = integrase inhibitor Enfuvertide = fusion inhibitor Nevirapine, Efavirenz, Delaverdine = NNRTI All others = NRTI
What is the mechanism of Triptan drugs?
Sumatriptan:
Presynaptic 5-HT(1B/1D) agonist
It inhibits functioning of trigeminal nerve & release of vasoactive peptide –> reduces neurogenic inflammation & causes vasoconstriction
Where is airway resistance the greatest?
Half of airway resistance comes from the upper airways (nose, pharynx)
In the lower airways, resistance increases between the 2-5th bronchial generations due to turbulent flowbut then decreases due to ^ in cross-sectional area & laminar flow.
Describe the innervation of the larynx
Vagus nerve –> Superior laryngeal n. & recurrent laryngeal n.
Superior laryngeal nerve:
External branch –> motor to cricothyroid muscle
Internal branch –> sensory above the vocal cords
Recurrent laryngeal nerve –> motor to all other laryngeal muscles; sensory below the vocal cords
Describe the events of oxidative phosphorylation
Complex I: NADH is oxidized, 1 H+ is pumped (into intermembranous space)
Complex II: FADH2 is oxidized, no H+ is pumped
Complex III: 1 H+ is pumped
Complex IV: 1 H+ is pumped
Complex V: ATP synthase –> each proton allowed back into mitochondrial matrix = 1 ATP
What is the mechanism of Rotenone?
Inhibits ETC complex 1 (RotenONE)
Decreased proton gradient
What is the mechanism of cyanide?
Cyanide & CO inhibit Complex IV of the ETC
Decreased proton gradient
What is the mechanism of Antimycin A?
Inhibits complex III of the ETC
decreased proton gradient
What is the mechanism of Oligomycin?
Directly inhibits ATP synthase
^ proton gradient
What are the irreversible enzymes in gluconeogenesis?
“Pathway Produces Fresh Glucose”
Pyruvate carboxylase
(mitochondria; Pyruvate –> Oxaloacetate)
PEP Carboxykinase
(cytosol; Oxaloacetate –> Phosphoenolpyruvate)
Fructose-1,6-Bisphosphatase
(cytosol)
Glucose-6-Phosphatase
(ER)
What are the primary gluconeogenic precursors?
Lactate Glycerol Alanine Glutamine (account for 90% of gluconeogenesis)
Where does gluconeogenesis occur?
Liver»_space; Kidney, Intestinal epithelium
What is the purpose of HMP shunt pathway?
The pentose phosphate pathway (HMP shunt) provides:
Ribose-5-P for nucleotide synthesis (pentose)
NADPH for reductive reactions (Phosphate)
(used to reduce Glutathione, produces ROI for resp. burst)
What are the steps of the HMP shunt pathway?
Oxidative:
Glu-6-P –> 2 NADPH + Ribulose-5-P
(G6PD; Irreversible; Rate-limiting)
Non-oxidative:
Ribulose-5-P –> Ribose-5-P or Glycerol-3-P or Fructose-6-P
(Phosphopentose isomerase transketolases; Reversible; Requires B1)
What are the steps involved in the synthesis of ROI’s for respiratory burst?
1) O2 –> Superoxide (O2-)
(NADPH Oxidase; Requires NADPH; Def. in CGD)
2) O2- –> H2O2
(Superoxide dismutase)
3) H2O2 + Cl- –> HOCl-
(Myeloperoxidase; Produces hypochlorite/bleach)
H202 can be inactivated by bacterial catalase or endogenous glutathione peroxidase
What are the common precipitants of hemolysis in a G6PD patient?
Infection Fava beans Sulfa drugs Primaquine Dapsone
What is seen on a blood smear in G6PD deficiency?
Heinz Bodies - Oxidized Hb
Bite cells - splenic macrophages take a bite out of RBC’s to remove heinz bodies
What is the process of fructose metabolism to enter glycolysis?
Fructose –> Fructose-1-P
(Fructokinase)
Fructose-1-P –> DHAP + Glyceraldehyde
(Aldolase B)
Glyceraldehyde –> Glyceraldehyde-3-P
(Triose kinase)
What is deficient in Essential fructosuria?
What is seen?
Aut. recessive defect in Fructokinase
Fructose appears in blood & urine
(Benign disease, as are both fructose disorders when compared to their galactose counterparts)
What causes Fructose intolerance?
What is seen?
Aut. recessive deficiency of Aldolase B
Fructose-1-P accumulates, taking away phosphate groups from glycogenolysis & gluconeogenesis
Symptoms:
Hypoglycemia, jaundice, cirrhosis, vomiting
What is the treatment for fructose/galactose metabolism disorders?
Exclude from diet.
Fructose –> exclude fructose & sucrose
Galactose –> exclude galactose & lactose
What are the steps in the metabolism of galactose to glucose?
Galactose –> Gal-1-P
(Galactokinase)
Gal-1-P –> Glucose-1-P
(Gal-1-P Uridyltransferase/GALT; Requires UDP-Glu from 4-epimerase)
What are the galactose metabolic disorders?
What is seen?
Galactokinase deficiency: Galactose in blood/urine Infantile cataracts (Galactose --> Galactitol shunt)
Classic Galactosemia (GALT deficiency): Failure to thrive Jaundice E. coli sepsis Infantile cataracts Mental retardation Hepatomegaly
What is the polyol pathway?
What are its components?
It’s an alternative method for trapping glucose within a cell (vs. hexokinase/glucokinase).
Steps:
Glucose –> Sorbitol
(Aldose reductase)
Sorbitol –> Fructose
(Sorbitol dehydrogenase; Not present in Schwann, retina, kidney)
What tissues have Aldose reductase?
What tissues have insufficient Sorbitol dehydrogenase?
Both enzymes:
Liver, lens, ovaries, seminal vesicles
Insufficient Aldose Reductase:
Retina, Schwann cells, kidneys
What does Aldose reductase catalyze?
Glucose –> Sorbitol
Galactose –> Galactitol
What are the essential amino acids?
PVT. TIM HALL
Phe Val Thr Trp Ile Met His Arg Leu Lys
Always Argues, never Tyres
**His & Arg are semi-essential (required during growth)
What is the purpose of the cori cycle?
Alanine cycle?
Cori cycle: Converts lactate & pyruvate to glucose for export to tissues
Alanine cycle: Alanine carries amino groups to liver
What is the function of ALT
AST?
ALT:
Alanine + alpha-Ketoglutarate –> Pyruvate + Glutamate
(Part of alanine cyle; Glutamate enters urea cycle; Pyruvate enters gluconeogenesis)
AST:
Glutamate + Oxaloacetate –> alpha-Ketoglutarate + Aspartate
(alpha-Ketoglutarate can then be used in alanine or TCA cycle; Aspartate can enter urea cycle; Glutamate can also enter urea cycle directly through deamination)
What is the rate-limiting step in the urea cycle?
Carbamoyl phosphate synthetase I
CO2 + NH4+ (+2ATP) –> Carbamoyl phosphate
It’s the first step
What are the intermediates in the urea cycle?
“Ordinarily, Careless Crappers Are Also Frivolous About Urination”
Ornithine \+Carbamoyl phosphate Citrulline \+Aspartate Arginosuccinate -Fumarate Arginine Urea
What is seen with ammonia intoxication?
What is the treatment?
Symptoms: Asterixis, slurred speech, somnolence, vomiting, cerebral edema, blurred vision
Treament:
Lactulose - acidifies GI lumen –> ^ excretion of NH4+
Limit dietary protein
Benzoate/Phenylbutyrate –> bind AA’s –> ^ excretion
What amino acids are these derived from? Dopamine/NE/EPI Serotonin/Melatonin Heme Histamine Creatine Urea NO GABA Glutathione
Dopamine/NE/EPI = Phenylalanine (converted to Tyr first) Serotonin/Melatonin = Tryptophan Heme = Glycine Histamine = Histidine Creatine/Urea/NO = Arginine GABA/Glutathione = Glutamate
What are the steps & enzymes involved in catecholamine synthesis?
Phenylalanine –> Tyrosine
(Phenylalanine hydroxylase; requires tetrahydrobiopterin)
Tyrosine –> DOPA (dihydroxyphenylalanine)
(Tyrosine hydroxylase; requires tetrahydrobiopterin)
DOPA –> Dopamine
(Dopa decarboxylase; requires B6)
Dopamine –> NE
(Dopamine beta-hydroxylase; requires Vit. C)
NE –> EPI
(Phenylethanolamine N-methyltransferase; requires SAM)
What causes PKU?
What is seen in PKU?
Phenylalanine hydroxylase (Phe –> Tyr) deficiency or tetrahydrobiopterin (cofactor; 2% of cases) deficiency.
Symptoms: Mental retardation Growth retardation Fair skin Eczema Musty/Mousy body odor Phenylacetate/Phenyllactate/Phenylpyruvate in urine
What is the treatment for PKU?
Avoid phenylalanine (artificial sweeteners) Increase Tyrosine intake
What is the danger of maternal PKU?
If uncontrolled during pregnancy, child will be affected (mental/growth retardation, cardiac abn) despite the child being a heterozygote.
What causes Onchronosis?
What is seen?
Alkaptonuria = a congenital deficiency of homogentistic acid oxidase (Tyr –> Fumarate to degrade Tyr).
Symptoms:
Dark connective tissue (ears, nose, cheeks) & sclera
Urine turns black when exposed to air
Severe arthralgias
What causes albinism?
Ocular albinism = X-linked
Generalized albinism = varies
Defect is either in tyrosinase (Tyr –> melanin) or in Tyrosine transporters (decreased Tyr available). Can also result from a lack of neural crest cell migration.
What causes homocysteinuria?
What is the treatment?
Three forms:
1) Cystathione synthase deficiency
Tx: Decreased Met in diet & ^ Cysteine, B12, Folate
2) Decreased affinity of cystathione synthase for B6
Tx: ^^ dietary B6
3) Homocysteine methyltransferase deficiency
What is seen in Homocystinuria?
^^ Homocysteine in urine Cysteine is essential Mental retardation Osteoporosis Tall stature Kyphosis Lens subluxation Stroke/MI
What causes Cystinuria?
What is seen?
How is it treated?
Hereditary defect in renal reabsorption of COAL (Cysteine, Ornithine, Arginine, Lysine) –> Staghorn calculi
Think of this if recurrent kidney stones seen in a young pt.
Tx: Good hydration & urinary alkalinization
What causes Maple Syrup Urine Disease?
What is seen?
Congenital deficiency of alpha-ketoacid dehydrogenase –> no degradation of branched amino acids.
“I Love Vermont maple syrup” (Ile, Leu, Val)
Symptoms:
CNS defects/Mental retardation
Death
Urine smells like burned sugar
How is Cistinuria diagnosed?
1) Hexagonal crystals in urine
2) Sodium Cyanide-Nitroprusside test (detects sulfhydryl groups; purple –> + result)
What causes Hartnup disease?
What is seen?
Hereditary disorder preventing neutral amino acid transport in the kidney & intestine –> Tryptophan not absorbed in gut & ^ excretion in urine –> Pellegra (Niacin deficiency).
How is glyogenolysis stimulated/inhibited in muscle?
Glucagon (live only) or EPI (liver & muscle –> ^ cAMP –> PKA –> activated Glycogen phosphorylase kinase –> Activated Glycogen phosporylase
Insulin –> Receptor tyrosine kinase –> Protein phosphatase –> inactive Glycogen phosphorylase
**Ca2+/Calmodulin can also activate Glycogen phosphorylase kinase to coordinate glycogenolysis in active muscle
What type of bonding is seen in glycogen?
alpha (1,6) = straight
alpha (1,4) = branch
What are the names of the glycogen storage diseases?
“Viagra Pills Cause A Massive Hard-on”
Type I = von Gierke's II = Pompe's III = Cori's IV = Anderson's V = McArdle's VI = Her's
What causes von Gierke’s disease?
How does it present?
Glucose-6-Phosphatase deficiency
Symptoms: Severe fasting hypoglycemia ^^ Liver glycogen --> Hepatomegaly ^ Blood lactate Fat cheeks, thin extremities
What causes Pompe’s disease?
Lysosomal alpha-1,4-glucosidase deficiency
Symptoms:
Cardiomegaly (Pompe’s trashes the pump)
Systemic findings
Early death
What causes Cori’s disease?
What is seen?
Debranching enzyme (alpha-1,6-glucosidase) deficiency
Symptoms:
Milder form of Type I (gluconeogenesis intact)
Hepatomegaly
Fasting hypoglycemia
What causes McArdle’s disease?
What is seen?
Skeletal muscle glycogen phosphorylase deficiency
Symptoms:
Painful muscle cramps & myoglobinuria with exercise
Often presents in early 20’s
Which LSD’s are associated with Ashkenazi Jews?
Tay-Sachs
Niemann Pick
Gaucher’s
Which LSD’s are X-linked recessive?
Fabry’s
Hunter’s
All others are autosomal recessive
What causes Fabry’s disease?
How does it present?
alpha-galactosidase A deficiency –> ceramide trihexoside accumulation
Symptoms:
Glove & stocking neuropathy
Angiokeratomas
Cardiovascular/renal disease
What causes Gaucher’s disease?
What is seen?
Glucocerebrosidase deficiency –> glucocerebrosidase accum.
Symptoms: HSM Aseptic necrosis of femur Bone crises Gaucher's cells (crumpled macrophages) Thrombocytopenia & anemia
What causes Niemann-Pick disease?
What is seen?
Sphingomyelinase deficiency –> Spingomyelin accum.
Symptoms: HSM Progressive neurodegeneration/Developmental delay Cherry red spot on macula Foam cells
What causes Tay-Sach’s disease?
What is seen?
Hexosaminidase A deficiency (Tay-SaX) –> GM2 ganglioside accum.
Symptoms: Progressive degeneration/Developmental delay Cherry red spot on macula Lysosomes with onion skin appearance NO HSM (vs. Niemann-Pick)
What causes Krabbe’s disease?
What is seen?
Galactocerebrosidase deficiency
Symptoms: Peripheral neuropathy Developmental delay Optic atrophy Globoid cells
What causes Metachromatic Leukodystrophy disease?
What is seen?
Arylsulfatase A deficiency –> Cerebroside sulfate accum.
Symptoms:
Central & peripheral demyelination
Ataxia
Dementia
What causes Hurler’s syndrome?
What is seen?
alpha-L-iduronidase deficiency –> Heparin & Dermatin sulfat accum.
Symptoms: Developmental delay Gargoylism Airway obstruction Corneal clouding HSM Gibbus deformity
What causes Hunter’s syndrome?
What is seen?
Iduronate sulfase deficiency –> Heparin & Dermatin sulfate accum.
Symptoms:
Mild Hurler’s dz but aggressive behavior & no corneal clouding
Hunters are aggressive men & must see clearly
What intermediate is used to synthesize fatty acids?
Citrate –> Acetyl-CoA –> Malonyl-CoA –> Fatty acid
How does Carnitine deficiency present?
Inability to transport long chain FA’s into the mitochondria for beta oxidation –> Weakness, hypoketotic hypoglycemia
What are the ketone bodies?
What are they formed from?
Acetoacetate
Acetone
beta-Hydroxybutyrate
They are formed from the oxidation of FA’s –> Acetyl-CoA. When TCA intermediates are depleted (Oxaloacetate) –> Ketogenesis instead
When are ketone bodies seen?
Prolonged starvation
Alcoholics (Oxaloacetate is depleted due to –> to malate)
DKA (Oxaloacetate is depleted from gluconeogenesis)
What is the progression of metabolic fuel usage during exercise?
ATP
Creatinine (seconds)
Anaerobic glycolysis (minutes-1h)
Aerobic metabolism & FA oxidation (surpasses anaerobic glycolysis @ 1h)
How does Aspirin overdose cause fever?
Uncouples ETC –> electron transport continues but no ATP is produced –> Heat
What is the function of the following apolipoproteins? E A-I C-II B-48 B-100
E --> mediates remnant uptake A-I --> Activates LCAT C-II --> Lipoprotein lipase cofactor B-48 --> Mediates chylomicron secretion B-100 --> Binds LDL receptor
What are the functions of the various Lipoproteins?
Chylomicron - Delivers dietary TG’s to peripheral tissue & cholesterol to the liver.
VLDL - Secreted by liver to deliver hepatic TG’s to peripheral tissue
IDL - Degradation product of VLDL; returns to liver
LDL - Delivers hepatic cholesterol to peripheral tissues; taken up into target tissues via LDLR; formed via hepatic lipase modification of IDL
HDL - Reverse cholesterol transport from periphery to liver; acts as repository for ApoC & ApoE; secreted by liver & intestine
What causes Type I familial dyslipidemia?
What is seen?
Lipoprotein lipase deficiency or altered C-II –> ^ chylomicrons, TG, cholesterol
Symptoms/Risks: Pancreatitis HSM Xanthomas No ^ risk for atherosclerosis
What causes Type IIa familial dyslipidemia?
What is seen?
Autosomal dominant. Absent or reduced LDLR –> ^^LDL, cholesterol
Symptoms:
Early atherosclerosis
Achilles xanthomas
Corneal arcus (blue ring @ outside of iris)
What causes Type IV familial dyslipidemia?
What is seen?
Autosomal dominant. Hepatic overproduction of VLDL.
Causes pancreatitis
What causes Abetalipoproteinemia?
Aut recessive mutation in Microsomal TRG Transfer Protein (MTP) gene –> reduced B-48 & B-100 –> reduced chylomicron & VLDL synthesis
What are the symptoms of abetalipoproteinemia?
Seen in the first few months of life Failure to thrive Steatorrhea Acanthocytosis (spur cells; Vit. E) Ataxia Night blindness (Vit. A)
Intestinal biopsy - Lipid accumulation within enterocytes
What is seen with TCA overdose?
TCCAA
Temperature (hyperpyrexia) Convulsions Coma Arrhythmia Apnea
What type of foods often contain S. aureus food poisoning (pre-formed toxin)?
Picnic foods, especially containing mayonnaise.
How do eosinophils function in parasitic infections?
Their IgE-specific Fc receptors bind IgE on opsonized parasites & they degranulate (antibody-dependent cytotoxicity)
What types of drugs are typically hepatically eliminated?
Lipophilic drugs
Anti-CCP Antibodies
Anti-cyclic citrullinated peptide Ab’s –> Rheumatoid arthritis
What signaling molecules use the JAK/STAT pathway?
Colony-simulating factors
Prolactin
Growth hormone
What is the most rapidly metabolized sugar via glycolysis?
Fructose
This is because it enters the glycolytic pathway after the rate-limiting step of glycolysis (PFK-1)
Which penicillins are anti-pseudomonal?
Cephalosporins?
Aminoglycosides?
Fluoroquinolones?
Pen = Ticarcillin, Piperacillin Ceph = Ceftazidime, Cefepime Aminogly = Tobramycin, Gentamycin, Amikacin FQ = Ciprofloxacin, Levofloxacin
Also Aztreonam, Imipenem, Meropenem
What is provided in chocolate agar?
Chocolate agar is required for H. influenzae culture. It provides:
Factor V = hematin
Factor X = NAD+
What is the urinary metabolite for serotonin?
5-HIAA
5-Hydroxyindoleaceticacid
What anti-mycobacterial agents work on intracellular bacteria?
Pyrazinamide - it works best at acidic environments like within a phagosome
The others (RIES) work on extracellular bacteria best.
What other abnormalities are commonly seen alongside imperforate anus?
Genitourinary abnormalities
What is seen in myeloperoxidase deficiency?
Candida infections
What is observed with apoptosis?
Pyknosis (shrinkage) Karyorrhexis (fragmentation) --> DNA laddering (180 bp intervals) Karyolysis (destruction of chromatin) Cell shrinkage Apoptotic body formation
What induces intrinsic apoptosis?
Extrinsic?
Intrinsic:
Withdrawal of growth factor
Injury (radiation, hypoxia)
Extrinsic:
FasL binding to Fas receptor
Granzyme B (enters via perforin; CTL’s)
Where does liquefactive necrosis occur?
Fat necrosis?
Fibrinoid necrosis?
Gangrenous necrosis?
Liquefactive = brain, bacterial abscesses, pancreas
Fat necrosis = peripancreatic fat, breast
Fibrinoid necrosis = blood vessels (malignant HTN, vasculitis)
Gangrenous necrosis = extremities & GI
(Can be dry (mummy) or wet (bacterial infection)
What type of calcification is seen with normal Ca2+ levels?
Dystrophic calcification = normal serum [Ca2+]
Metastatic calcification = ^^ [Ca2+]
What is seen with irreversible cell damage?
Reversible?
Irreversible: Disruption of 3 membranes -Plasma membrane -Mitochondrial membrane (Cyt. C) - Lysosomal membrane
Reversible:
Cell swelling (due to reduced ATP –> reduced pump action)
Ribosomal detachment
Fatty change
What cells are affected in Hypoxic Ischemic Encephalopathy?
HIE affects:
- Pyramidal cells of hippocampus
- Purkinje cells of cerebellum
What are the cell-mediators of the cardinal signs of inflammation?
Calor/Rubor = Histamine, Prostaglandins, Bradykinin Tumor = Histamine, Tissue damage Dolor = Bradykinin & PGE2
Where does leukocyte extravasation occur?
The post-capillary venules
This is the site of vascular permeability
What are the steps of leukocyte extravasation & their mediators?
1) Margination (occurs due to vasodilation)
2) Rolling (P/E-selectin binds Sialyl-Lewis)
3) Adhesion (ICAM-1 binds LFA-1 = integrin)
4) Diapedesis (PECAM-1 binds itself)
5) Migration (CILK: C5a, IL-8, LTB4, Kallikrein)
What is released from Weibel-Palade bodies?
von Willebrand Factor
P-selectin
What are the stages of wound healing?
1) Inflammatory (immediate)
2) Proliferative (2 days; granulation tissue, collagen (III), contraction by myofibroblasts)
3) Remodeling (1 week; Type III collagen –> Type I)
What dietary deficiencies can slow wound healing?
Ascorbic acid - required for collagen hydroxylation –> crosslinks
Copper - crosslinking enzyme requires it
Zinc - collagenase requires it
What diseases cause granuloma formation?
MTB Fungal infections Syphilis Leprosy Bartonella hensalae (cat scratch disease) Sarcoidosis Crohn's disease Wegener's Churg-Strauss Berylliosis/silicosis
What causes exudative fluid?
Either inflammation or lymphatic obstruction
