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
What is the specific gravity of transudate vs. exudate?
Transudate < 1.012
Exudate > 1.020
What conditions can lower ESR?
Sickle cell
Polycythemia
CHF
What stain is used to detect amyloidosis?
Congo red stain
Lights up with “apple green birefringence” under polarized light
What are the systemic amyloidoses and their causes
AL (primary) amyloisosis:
Plasma cell dyscrasia or Multiple myeloma –> Ig light chain deposition
AA (secondary) amyloisosis:
Chronic inflammatory dz (RA, IBD, chronic infx), cancer, Familial Mediterranean fever –> Amyloid A (acute phase reactant)
What is seen with systemic amyloidosis?
Nephrotic syndrome Restrictive cardiomyopathy Easy bruising Hepatomegaly Neuropathy
What causes dialysis-related amyloidosis?
What is seen?
Beta-2-microglobulin deposits in joints –> carpal tunnel & joint issues
What causes Heritable amyloidosis?
What is seen?
MUTATED Transthyretin deposition in heart & brain
What causes Alzheimer’s disease?
Deposition of beta-amyloid (from amyloid precursor protein) in the brain
*APP is located on chromosome 21 (why Down’s causes early-onset Alzheimer’s)
By what means do cancers tend to metastasize?
Carcinomas = lymphatics Exceptions: -Renal cell carcinoma -HCC -Follicular thyroid carcinoma -Choriocarcinoma
Sarcomas = hematogenous
How can clonality of a possible neoplasia be determined?
Females - G6PD expression (alleles should be 1:1)
B-cell tumors = Ig light chain (normal k:L = 3:1)
What -plasia’s are reversible & irreversible?
Reversible = Hyperplasia, Metaplasia, Dysplasia
Irreversible = Anaplasia, Neoplasia, Desmoplasia
What cancers is ionizing radiation associated with?
Leukemias
Papillary thyroid cancer
Breast cancer
What are the characteristic intermediate filaments in the following tissues? Mesenchyme Neuroglia Muscle Neurons Epithelium
Mesenchyme = Vimentin Neuroglia = GFAP Muscle = Desmin Neurons = Neurofilaments Epithelium = Keratin
What is chromogranin a tumor marker for?
Neuroendocrine tumors
What cancers stem from myc dysfunction?
myc = a transcription factor
c-myc –> Burkitt’s lymphoma
L-myc –> small cell Lung carcinoma
N-myc –> Neuroblastoma
What cancer is c-kit found in?
GIST
What tumor is BRAF mutated in?
Melanoma
What do the Rb and p53 genes do?
Rb:
Inhibits E2F
G1–>S tumor suppressor
p53:
Transcription factor for p21
G1–>S tumor suppressor
What is CEA a tumor marker for?
Colorectal & Pancreatic carcinoma
*Very nonspecific
What is AFP a tumor marker for?
Hepatocellular carcinoma
Yolk sac tumors
What is CA-125 a tumor marker for?
Ovarian cancer
What is S-100 a tumor marker for?
Melanoma
Neural tumors
Schwannoma
What is Alkaline phosphatase a tumor marker for?
Mets to bone
Paget’s dz of the bone
What is Bombesin a tumor marker for?
Neuroblastoma
Lung/gastric cancer
What is TRAP a tumor marker for?
Tartrate-Resistant Acid Phosphatase
Hairy cell leukemia
TRAP the hairy animal
What is CA-19-9 a tumor marker for?
Pancreatic adenocarcinoma (19-9 = 10 = the # of letters in "pancreatic")
What types of neoplasms can EBV cause?
Burkitt’s lymphoma
Hodgkin’s lymphoma
Nasopharyngeal carcinoma
CNS lymphoma (immunocompromised pts)
What type of cancer can aflatoxins cause?
HCC
What type of cancer can vinyl chloride cause?
Liver angiosarcoma
What type of cancer can nitrosamines cause?
(smoked foods) –> gastric adenocarcinoma (intestinal type)
What type of cancers can cigarette use cause?
Mouth/Esophageal/larynx Lung Pancreas Kidney Bladder
What type of cancer(s) can arsenic cause?
SCC (skin; like the women who used it to lighten their skin)
Liver angiosarcoma
What type of cancer(s) can naphthalene cause?
Aniline dyes –> Transitional cell carcinoma (bladder)
What types of cancers are associated with alcohol?
SCC of the mouth & esophagus
HCC (via cirrhosis)
Pancreatic (not a risk factor; but chronic pancreatitis is)
What type of cancer is associated with the following paraneoplastic syndrome?
ACTH
Clinically –> Cushing’s syndrome
Small cell lung carcinoma
What type of cancer is associated with the following paraneoplastic syndrome?
ADH
SIADH
Small cell lung carcinoma
Intracranial neoplasms
What type of cancer is associated with the following paraneoplastic syndrome?
PTHrp
Clinically –> Hypercalcemia
Squamous cell lung cancer
Renal cell cancer
Breast cancer
*The most common cause of clinically apparent hypercalcemia = cancer
What type of cancer is associated with the following paraneoplastic syndrome?
Calcitriol
Clinically –> Hypercalcemia
Lymphoma
What type of cancer is associated with the following paraneoplastic syndrome?
EPO
Clinically –> Polycythemia
Renal cell carcinoma
Hemangioblastoma
HCC
Pheochromocytoma
What cancers are psamomma bodies seen in?
PSaMMoma: Papillary thyroid Serous cystadenocarcinoma Meningioma Mesothelioma
What are the leading cancers in incidence?
Deaths?
Incidence = Breast/Prostate, Lung, CRC Deaths = Lung, Breast/Prostate, CRC
Cancer is the 2nd leading cause of death in the U.S.
What mets go to brain?
Lung > Breast > GU > Osteosarcoma > Melanoma > GI
50% of brain cancer is mets (usually at gray/white junction)
What metastasizes to the liver?
CRC»_space; stomach > pancreas
What metastasized to the bone?
Prostate = Breast > lung > thyroid = testes
What families do each of the viral hepatitides belong to?
HAV = Picornavirus HBV = Hepadnavirus HCV = Flavivirus HDV = Deltavirus HEV = Hepevirus
What is the cause of propionic acidemia?
Propionyl-CoA carboxylase deficiency
Normally Valine or Isoleucine –> Propionyl-CoA
(branched chain alpha-ketoacid dehydrogenase)
then Propionyl-CoA –> Methylmalonyl-CoA
(propionyl-CoA carboxylase)
then Methylmalonyl-CoA –> Succinyl-CoA
(methylmalonyl-CoA isomerase)
–> TCA cycle.
What are the endoscopic & microscopic findings for Candida, HSV-1, & CMV esophagitis?
Candida:
grey/white pseudomembrane patches
Yeast & pseudohyphae
HSV-1:
Punched out ulcers
Molding, marginated, multinuclear w/ intranuclear inclusions
CMV:
Linear ulceration
Both intranuclear & cytoplasmic inclusions
What does the Prussian blue stain detect?
Intracellular iron
What causes hemosiderin-laden macrophages in the alveoli?
These are heart failure cells
Caused by left CHF –> ^ hydrostatic pressure in pulmonary capillaries –> RBC/heme leakage –> ingestion by macs
What is the first line drug for absence seizures?
What is the mechanism?
Ethosuximide
It blocks T-type Ca2+ channels in the thalamus
What anticonvulsants prolong Na+ channel recovery?
Phenytoin
Carbamazepine
Valproic acid
How does botulism commonly present?
Diplopia, dysphagia, dysphonia within 12-46h of ingestion.
Can be caused by:
- Improperly canned food
- Wound infection
- Honey (infantile botulism)
What is seen in normal cardiac aging?
Decreased apex-to-base dimensions Sigmoid shaped interventricular septum Myocyte atrophy with interstitial fibrosis Lipofuscin accumulation (byproducts of lipid metabolism)
What cell surface markers are absent in PNH?
CD55 & CD59
What is recommended regarding GBS and pregnancy?
Vaginal/rectal culture at 35-37 weeks. If positive –> intrapartum ampicillin (or penicillin)
What anti-herpesvirus drugs require activation by viral enzymes?
Acyclovir- requires activation by HSV/VZV viral thymidine kinase
Gancyclovir - requires activation by CMV viral kinase
Cidofovir - does not require any activation
*All are viral DNA polymerase inhibitors
How does Ondansetron work?
It’s a 5-HT3 antagonist:
1) Blocks vagal nerve stimulation of the medulla oblongata
2) Blocks central chemoreceptor trigger zone
What is Km?
What determines Vmax?
Km = the concentration needed for 50% enzyme saturation
(inversely related to affinity)
Vmax is directly related to enzyme concentration
Lineweaver-Burk plots:
What determines the X intercept?
Y intercept?
Slope?
X intercept = 1/(-Km)
Y intercept = 1/Vmax
Slope = Km/Vmax
What kinetics variable do competitive inhibitors affect?
Noncompetitive inhibitors?
Competitive inhibitors increase Km –> decrease potency
Noncompetitive inhibitors decrease Vmax –> decrease efficacy
What is the equation for bioavailability?
F = (AUCoral)/(AUCiv)*100
What is the equation for volume of distribution?
Vd = Amount of drug in the body/plasma drug concentration
It is the theoretical volume of fluid needed to maintain a constant dose at a constant plasma concentration.
What types of drugs have low vs high volumes of distribution?
Low Vd:
Large/charged molecules
Plasma protein bound
High Vd:
Lipophilic molecules
Tissue protein bound
What is the equation for half life?
HL = (0.7*Vd)/CL
*A property specific to first-order kinetics (constant % of drug eliminated)
What is the equation for drug clearance?
CL = (rate of elimination of the drug)/(plasma drug concentration) CL = Vd*Ke --------where Ke is the elimination constant
It’s given in units of flow
How quickly do constant infusions of drugs reach steady state?
Takes 4-5 half lives
Steady state is a function of half-life, therefore dosing frequency, size, loading doses, etc. have no effect on the time it takes to reach steady state
What is the equation for drug loading dose?
Maintenance dose?
LD = Target plasma concentration*(Vd/F)
MD = Target plasma concentration*(CL/F)
Renal or liver disease –> lower maintenance dose (only)
What drugs have zero-order elimination?
PEA (round like 0):
Phenytoin
Ethanol
Aspirin
How can urine pH affect renal elimination of a drug?
Ionized form cannot traverse membranes:
Weak acids are trapped in alkaline urine
(give IV HCO3)
Weak bases are trapped in acidic urine
(give IV NH4Cl)
What occurs during Phase I & Phase II drug metabolism?
Phase I:
REDOX, CYP450 –> slightly polar metabolites (often still active)
Phase II:
GAGS: Glucuronidation, Acetylation, Glutathione, Sulfation
Usually yields inactive, very polar metabolites for urine excretion
What phase of drug metabolism decreases first with age?
Phase I is affected first
What is the equation for therapeutic index?
Therapeutic window?
TI = LD50/ED50
TW = min. effective dose - min. toxic dose
What sympathetic structures are innervated by ACh?
Sweat glands
Adrenal medulla
All others are preganglionic ACh & postganglionic NE or Dop.
What autonomic drugs act on what G-proteins & second messengers?
HAV 1 M&M = H1, a1, V1, M1, M3 –> Gq
MAD 2’s = M2, a2, D2 –> Gi
All others = Gs
What are the sequences of the autonomic second messenger systems?
Gq –> Phospholipase C (cleaves PIP2) –> DAG & IP3
DAG –> PKC
IP3 –> Ca2+ influx –> smooth muscle contraction
Gi -/-> Adenylyl cyclase
Gs –> Adenylyl cyclase –> ^ cAMP –> PKA –>
–> ^Ca2+ (in heart) or ^MLCK activity
What do alpha adrenergic receptors control?
Alpha1:
Vascular smooth muscle contraction
Mydriasis
Intestinal & bladder sphincter contraction
Alpha2: Lowers central sympathetic outflow Lowers insulin release Lowers lipolysis Causes platelet aggregation
Where do muscarinic receptors act?
M1 = CNS, enteric nervous system M2 = decreases HR & contractility of atria M3 = exocrine glad secretions, gut peristalsis, bladder contraction, bronchoconstriction, miosis, accommodation
Where do dopamine receptors act?
D1 = relaxes renal vascular smooth muscle
D2 modulates NT release in the brain
Where do histamine receptors act in the body?
H1 = nasal & bronchial mucus production, bronchiolar constriction, pruritis, pain
H2 = gastric acid secretion
Where does vasopressin act in the body?
V1 = vascular smooth muscle contraction V2 = water reabsorption in the kidney
What is the mechanism of Bethanechol?
What is it used for?
Cholinomimetic used to activate bladder & bowels.
postop ileus, neurogenic ileus, urinary retention
What is the mechanism of Carbachol?
What is it used for?
Cholinomimetic used for glaucoma, pupillary contraction.
What is the mechanism of Pilocarpine?
What is it used for?
Cholinomimetic that stimulates sweat, tears, saliva. Used for open-angle and closed-angle glaucoma.
“You cry, drool, and sweat on your pilo (pillow)”
What is the mechanism of Methacholine?
What is it used for?
It is a cholinomimetic used in the challenge test to diagnose asthma.
What is the mechanism of Neostigmine?
What is it used for?
It is an anticholinesterase inhibitor used for:
Postop/neurogenic ileus & urinary retention
Myasthenia gravis
Postop reversal of neuromuscular junction blockade
*Neo (no) CNS penetration
What is the mechanism of Pyridostigmine?
What is it used for?
It is a long acting anticholinesterase inhibitor used for myasthenia gravis treatment
*It does not cross the BBB
What is the mechanism of Edrophonium?
What is it used for?
It is a short-acting acetylcholinesterase inhibitor used to diagnose myasthenia gravis.
What is the mechanism of Physostigmine?
What is it used for?
It is a acetylcholineesterase inhibitor used to treat anticholinergic overdose (crosses the BBB).
“Physostigmine phyxes atropine overdose”
What is the mechanism of Donepezil?
What is it used for?
It is an acetylcholinesterase inhibitor used to treat Alzheimer’s disease.
What is seen with cholinesterase inhibitor poisoning?
Due to compounds that irreversible bind AChE (organophosphates)
DUMBBELSS: Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle & CNS Lacrimation Sweating Salivation
What is the mechanism of Benztropine?
What is it used for?
Muscarinic antagonist used for Parkinson’s disease.
“Park my Benz”
What is the mechanism of Scopalamine?
What is it used for?
Anti-muscarinic used for motion sickness.
What is the mechanism of Ipratropium?
What is it used for?
Ipratropium/Tiotropium are antimuscarinic drugs used in COPD & asthma.
What is the mechanism of Oxybutynin?
What is it used for?
It is an antimuscarinic drug used to reduce bladder spasms & alleviate urgency seen with mild cystitis
What is the mechanism of Glycopyrrolate?
What is it used for?
It is an antimuscarinic used preoperatively to reduce airway secretions
What is atropine used for?
What is seen with overdose?
Atropine is used to treat bradycardia & in ophthalmology.
Overdose:
“Hot as a hare, dry as a bone, red as a beet, blind as a bad, mad as a hatter”
What receptors does epinephrine act at?
What are its uses?
A1, A2, B1, B2
Used in anaphylaxis, open angle glaucoma, asthma, hypotension
What receptors does norepinephrine act at?
What are its uses?
A1, A2 > B1
Used for hypotension (but decreases renal perfusion)
What do beta adrenergic receptors control?
B1:
^ HR and contractility
^ renin release
^ lipolysis
B2: Vasodilation Bronchodilation ^ HR & contractility ^ lipolysis ^ insulin release Tocolysis Ciliary muscle relaxation ^ aqueous humor production
What are the effects of NE and Isopreterenol on heart rate?
NE –> alpha-adrenergic stimulation –> ^ BP –> reflex bradycardia
Isopreterenol –> beta-adrenergic stimulation –>B2 causes decreased BP –> reflex tacycardia (plus B1 stimulation ^ HR)
What receptors does isopreterenol act at?
What are its uses?
B1, B2
It is used in Torsades & bradyarrhythmias
Don’t use if ischemia is suspected (lowers BP and ^ HR)
What receptors does Dopamine act at?
What are its uses?
D1 > B1, B2, > A1, A2
Used for shock (helps renal perfusion), heart failure
Low dose = ^ RPF
Medium dose = ^ CO
High dose = lowered CO
What receptors does dobutamine act at?
What are its uses?
B1»_space; B2, A1, A2
Used for heart failure, cardiac stress testing.
What receptors does phenylephrine act at?
What are its uses?
A1, A2
Used for hypotension, ocular procedures (mydriasis), rhinitis (decongestant)
What receptors does albuterol act at?
What are its uses?
B2»_space; B1
Albuterol is used for acute asthma.
Salmeterol is used for long-term asthma or COPD control.
Terbutaline is used to reduce premature uterine contractions.
What receptors does Ritodrine act at?
What are its uses?
B2
Reduces premature contractions
What are the indirect sympathomimetics?
Amphetamine - releases stored catecholamines
Ephedrine - same as amphetamine
Cocaine - catecholamine reuptake inhibitor
(never give beta blockers to cocaine abuser, can cause unopposed alpha stimulation –> malignant HTN)
What receptors does clonidine act at?
What are its uses?
It is a centrally acting A2 agonist –> reduces central sympathetic outflow. It’s useful in HTN comorbid with renal disease because it does not reduce kidney perfusion.
What drug is used preoperatively for pheochromocytoma?
What is its mechanism?
Phenoxybenzamine is an irreversible alpha-adrenergic antagonist.
What is Phentolamine?
What is its use?
It is a reversible nonselective alpha-adrenergic antagonist. It is used to treat patients who are on MAOi’s and eat Tyramine.
What is Terazosin?
What is it used for?
Prazosin, Terazosin, Doxazosin, Tamsulosin
They are A1-selective adrenergic antagonists. They are used to treat HTN & urinary retention from BPH.
They can cause 1st dose orthostatic hypotension, dizziness, headache.
What is Mirtazapine?
What is it used for?
It is an alpha-2 blocker used to treat depression.
What are the uses for beta blockers?
Angina MI SVT (AV node) HTN (acts on heart and juxtaglomerular app. cells) CHF Glaucoma
What are the side effects of beta blockers?
Impotence
Asthma exacerbation
Bradycardia or AV block
CNS - seizures, sedation, sleep alteration
Use with caution in diabetics (mask hypoglycemia) & asthmatics
What are the B1-selectinve beta blockers?
BEAM: Betaxolol (partial agonist) Esmolol (short-acting)\ Atenolol Metoprolol
What are the nonselective beta blockers?
"Please Try Not Being Picky" Propranolol Timolol Nadolol Beta blockers yo Pindolol
What are the nonselective alpha & beta blockers?
Carvedilol
Labetalol
What are the beta-adrenergic partial agonists?
Partial Agonist:
Pindolol
Acebutolol
What is the treatment for a beta blocker overdose?
Glucagon
What is the treatment for a digitalis overdose?
KLAM treatment K+ normalization Lidocaine Anti-dig Fab fragments Mg2+
What is the treatment for a lead overdose?
EDTA
Dimercaprol
Penicillamine
What is the treatment for an iron overdose?
DeFeroxamine
What is the treatment for a Mercury overdose?
Dimercaprol
Succimer
What is the treatment for a copper overdose?
Penicillamine
What is the treatment for an arsenic/gold overdose?
Penicillamine
Dimercaprol
Succimer
What is the treatment for methemoglobin?
Methylene blue
What is the treatment for a benzodiazepine overdose?
Flumazenil
What is the treatment for a TCA overdose?
Alkalinize urine (NaHCO3)
What is the treatment for a heparin overdose?
Protamine sulfate
What is the treatment for a warfarin overdose?
Fresh frozen plasma
Vitamin K
What is the treatment for a tPA/streptokinas/urokinase overdose?
Aminocaproic acid
What is the treatment for a Theophylline overdose?
Beta blocker
What drugs cause flushing?
VANC: Vancomycin Adenosine Niacin Calcium channel blockers
What drugs can cause hemolysis in G6PD deficient patients?
"Hemolysis IS PAIN" INH Sulfa drugs Primaquine Aspirin Ibuprofen Nitrofurantoin
What drug can cause acute cholestatic hepatitis?
Erythromycin
What drugs can cause gynecomastia?
“Some Drugs Create Awkward Knockers”
Spironolactone Digitalis Cimetidine Alcohol (chronic) Ketoconazole
What drugs can cause hypothyroidism?
Lithium
Amiodarone
Sulfa drugs
What drugs can cause pulmonary fibrosis?
hard to BLAB when you have pulmonary fibrosis
BLeomycin
Amiodarone
Busulfan
What drugs can cause gingival hyperplasia?
Phenytoin
Verapamil
Cyclosporine
What drugs can cause myopathies?
Fish N CHIPS Give myopathies
Fibrates Niacin Colchicine Hydroxychloroquine Interferon-alpha Penicillamine Statins Glucocorticoids
What drugs can cause photosensitivity?
SAT for a photo
Sulfa drugs
Amiodarone
Tetracycline
What drugs can cause drug-induced lupus?
HIPP
Hydralazine
INH
Procainamide
Phenytoin
What drugs can cause seizures?
BITE MI tongue
Bupropion Imipenem Tramadol Enflurane Metaclopramide INH
What drugs are both nephrotoxic and ototoxic?
Aminoglycosides
Vancomycin
Loop diuretics
Cisplatin
What are the sulfa drugs?
Popular FACTSSS
Probenecid Furosemide Acetazolamide Celecoxib Thiazides Sulfa antibiotics Sulfasalazine Sulfonylureas
Match the suffix with the drug class:
- iptan
- caine
- azine
- etine
- ipramine/-triptyline
- tidine
- nib
- cept
- iptan = 5-HT1B/1D agonist
- caine = local anesthetic
- azine = neuroleptic, antiemetic
- etine = SSRI
- ipramine/-triptyline = TCA
- tidine = H2 antagonist
- nib = kinase inhibitor
- cept = receptor molecule
What is the upper limit of a normal ESR?
Men: age/2
Women: (age+10)/2
What causes senile systemic amyloidosis?
Deposition of normal TTR (Transthyretin)
What cancers is ret associated with?
MEN2A & MEN2B
Why is CVID unique?
Can be acquired in 20’s-30’s
What causes cauda equina syndrome?
What is seen?
Rupture of intervertebral disk –> compresses 2+ spinal nerves
Symptoms: Low back pain that radiates to legs Asymmetrical saddle anesthesia Loss of anocutaneous reflex Loss of knee & ankle jerk reflex (Generally unilateral) paraplegia
What causes conus medullaris syndrome?
What is seen?
Disk herniation, tumor, spinal fracture –> L2 lesion –> conus medullaris syndrome
Symptoms: Acute onset severe low back pain Urinary & fecal incontinence Impotence Saddle anesthesia (S3-S5) Generally spares legs (might see mild weakness)
What drugs can cause Torsades de pointes
Class III (Sotolol) & Class Ia (Quinidine) antiarrhythmics TCA's
What structures cease at the lung bronchi?
What cease at the terminal bronchioles?
Bronchi - Cartilage, goblet cells
Terminal bronchioles -
Pseudostratified ciliated columnar cells (mucociliary escalator)
Smooth muscle of the airways
What type of epithelia are found in the lung?
Bronchi & terminal bronchioles = Pseudostratified ciliated columnar epithelium
Respiratory bronchioles = cuboidal cells
Alveolar ducts & alveoli = simple squamous
What is the equation for collapsing pressure of alveoli?
P = 2(surface tension)/radius
What test shows lung maturity in a fetus?
Lecithin:Spingomyelin ratio > 2.0
<1.5 increases risk for NRDS
What are lamellar bodies?
Intracellular type 2 pneumocte inclusions. They contain phospholipids for production of surfactant.
What are club cells?
They are nonciliated columnar cells found in the small airways. They can degrade inhaled toxins (via CYP450) & act as reserve cells. They can also secrete substances to protect the bronchiolar lining.
Where do aspirates go in the lung?
Upright –> bottom of RLL
Supine –> top of RLL
How are the pulmonary artery & bronchus organized in the lungs?
Pulmonary artery is RALS to the bronchus:
Right anterior
Left superior
At what level do the main structures penetrate the diaphragm?
“I ate ten eggs at noon”
IVC = T8
Esophagus/Vagus = T10
Aorta/Azygous vein/Thoracic duct = T12
What are the accessory muscles of breathing?
Inspiration - External intercostals, SCM, scalenes
Expiration - Rectus abdominus, obliques, internal intercostals
What is the equation for total lung volume?
LITER:
tLc = IRV + TV + ERV + RV
What are typical pulmonary values for: TV FRC RV TLC
TV = 500 mL FRC = 2200 mL RV = 1200 mL TLC = 6000 mL
What are the two forms of HbA & their affinity for oxygen?
T = taut = low affinity for O2 R = relaxed = 300x higher affinity for O2
This is the basis for the positive cooperativity seen with Hb. Binding of O2 induces the relaxed form in the other Hb molecules.
What factors cause Hb to bind O2 less avidly in the tissues?
Increase in C-BEAT: CO2, Cl- BPG Exercise Acid/Altitude Temperature
“Taut in tissues, Relaxed in respiratory”
What causes HbF to have a higher affinity for O2 than HbA?
It does not efficiently bind 2,3-BPG
What causes Methemoglobinema?
How is it treated?
Nitrites oxidize Fe2+–>Fe3+ (cannot bind oxygen)
Use METhyline blue for METhemoglobinemia
What is the main problem with CO poisoning?
O2 cannot be unloaded in tissues because CO (higher affinity than O2 for Hb) holds Hb in the relaxed form. Causes left shift in the Hb dissociation curve.
How does myoglobin differ from hemoglobin?
It is found within muscle cells & is monomeric (Hb is tetrameric).
What gases are perfusion limited in the lung?
Diffusion limited?
Perfusion limited = O2 (health), N2O, CO2
Diffusion limited = CO
What is the equation for diffusion capacity?
V(gas) = (Area/Thickness)Diff. constant(P1-P2)
Emphysema –> decreased area
Fibrosis –> increased thickness
What is the cause of primary pulmonary hypertension?
Inactivating mutation in BMPR2 (normally inhibits vascular smooth muscle proliferation)
Seen in young women.
What defines pulmonary hypertension?
What can cause secondary pulmonary hypertension?
Pulmonary artery pressure > 25 mmHg
Causes of secondary PHTN: COPD Mitral stenosis Recurrent PE's Autoimmune disease Left-to-right shunt Sleep apnea Living at high altitude
What is the equation for pulmonary vascular resistance?
PVR = (Pulm art. Pressure - Wedge pressure)/Cardiac output
What is a normal O2 binding capacity?
15g/dL of Hb * (1.34 mlO2/gHb) = ~20 mLO2/dL
Cyanosis is seen when > 5g/dL of Hb is deoxygenated
What is the alveolar gas equation?
PAO2 = PIO2 - (PaCO2/R)
PIO2 = PO2 of inspired air = 150 mmHg R = respiratory quotient = CO2 produced/O2 consumed = 0.8
What is a normal A-a gradient?
What can cause an increased A-a gradient?
Normal = 10-15 mmHg
Increased in:
Right-to-left shunt
Diffusion limitation
V/Q mismatch
What are the causes of hypoxemia?
Which show an increased A-a gradient?
Normal A-a gradient:
High altitude
Hypoventilation
Increased A-a gradient:
Right-to-left shunt
Diffusion limitation
V/Q mismatch
What type of V/Q mismatch improves with supplemental O2?
High V/Q (dead space) should improve with O2
V/Q of 0 (shunt) will not improve with O2
What are the alveolar, arterial, and venous pressures like throughout the lung?
Zone 1 (apex) = A > a > v Zone 2 = a > A > v Zone 3 (base) = a > v > A
What part of the lung has a high vs. low V/Q
High V/Q in apex (dead space)
V/Q = 1 in the middle of the lung
Low V/Q in base (shunt)
*Note that the base is actually better ventilated than the apex, but it is much much better perfused –> low V/Q
How is CO2 carried in the blood?
1) Bicarbonate (90%)
2) HbCO2 (5%)
3) Dissolved CO2 (5%)
How does CO2 from the tissues cause O2 unloading?
CO2 –(carbonic anhydrase)–> H2CO3 H+ & HCo3- –> H+ binds Hb –> taut Hb –> O2 release.
The opposite happens in the lung due to high amount of O2. CO2 is released.
What changes occur at high altitude?
Acute ^ in ventilation –> decreased O2 & CO2
Chronic:
^ EPO
^ 2,3-BPG
^ renal excretion of bicarb (compensates for resp. alk.)
Chronic hypoxic vasoconstriction –> RVH
What changes in vascular O2 & CO2 are seen during exercise?
PaO2 & PaCO2 are unchanged
Venous O2 is decreased & venous CO2 is increased
What are the components of Virchow’s triad of hemostasis?
1) Stasis
2) Hypercoagulability
3) Endothelial damage
These predispose to coagulation.
What are the types of pulmonary emboli?
Fat (long bone fractures; hypoxemia + petechial rash) Gas (the bends, the chokes) Thrombus (95%) Bacteria Amniotic fluid (can cause DIC) Tumor
What defines chronic bronchitis?
Chronic productive cough lasting > 3 months total over the past 2 years
What is seen on spirometry in obstructive lung disease?
Restrictive lung disease?
Obstructive = LOW FEV1, low FVC –> lower FEV1/FVC
Restrictive = low FEV1, LOW FVC –> FEV1/FVC > 80%
Who are blue bloaters & pink puffers?
Why?
Chronic bronchitis = blue bloaters
They are constantly hypoxemic
RHF –> edema
Emphysema = pink puffers
They must work hard to breath
Puff their lips out when they exhale (PEEP)
What is the Reid index?
Thickness of the mucus gland layer in relation to the whole bronchial wall. It is > 50% in chronic bronchitis.
What causes centriacinar emphysema?
Panacinar emphysema?
Where are they seen?
Smoking –> centriacinar emphysema in upper lobes (more smoke)
A1AT deficiency –> panacinar emphysema in lower lobes (more blood)
What chromosome is asthma associated with?
Chromosome 5
What is seen histologically with asthma?
Curschmann’s spirals (shed epithelium plugs)
Charcot-Leyden crystals (from eosinophils)
What are the mediators of an asthma attack?
Early phase: Histamine, LTC4,D4,E4
Late phase: Inflammation; Major basic protein
What can cause bronchiectasis?
Cystic fibrosis Kartagener's Bronchial obstruction Smoking (poor ciliary motility) Bronchopulmonary aspergillosis
What are the causes of restrictive lung disease?
Idiopathic pulmonary fibrosis Pneumoconioses Hypersensitivity pneumonitis Sarcoidosis Drug toxicity (bleomycin, busulfan) Recurrent PE Also poor breathing mechanics (obesity, MG)
What lobes are affected in the pneumoconioses?
Anthracosis & silicosis –> upper lobes
Asbestosis –> lower lobes
What are the risks of the pneumoconioses?
Anthracosis - fibrosis
Silicosis - fibrosis, TB infection, bronchogenic carcinoma
Asbestosis - fibrosis, bronchogenic carcinoma, mesothelioma
When are adequate levels of surfactant produced in-utero?
Production begins at 28 weeks & is sufficient at 34 weeks
What are the risk factors for NRDS?
The treatment?
Risk factors:
Prematurity
Maternal diabetes (insulin decreases production)
C-section (glucocoricoids ^ production)
Treatment:
Intrapartum dexamethasone
Surfactant at birth
What complications are seen with NRDS?
Hypoxemia –> Necrotizing enterocolitis & PDA
Supplemental O2 –> Bronchopulmonary dysplasia & Retinopathy of the newborn
What can cause ARDS?
Trauma Sepsis Shock DIC Aspiration Uremia Acute pancreatitis Amniotic fluid embolism Hypersensitivity
What is seen histologically with pulmonary hypertension?
Plexiform lesions
Arteriosclerosis
Hypertrophy of the media
Intimal fibrosis
How does sleep apnea cause hypertension?
1) ^ release of catecholamines during night
2) Hypoxia –> ^ EPO –> ^ erythropoiesis
What are the complications of lung cancer?
SPHERE of complications: SVC syndrome Pancoast tumor Horner's syndrome Endocrine (paraneoplastic) Recurrent laryngeal (hoarseness) Effusions
What lung cancers are most vs. least common?
Metastases (breast, colon, prostate, bladder) Adenocarcinoma Squamous cell carcinoma Small cell carcinoma Large cell carcinoma Bronchial carcinoid tumor
Where does lung cancer metastasize?
Adrenals
Brain
Bone
Liver
What lung tumors are located centrally?
Peripherally?
Peripheral = adenocarcinoma, Large cell carcinoma
Central = Small cell carcinoma, Squamous cell carcinoma
What is the most common lung cancer in nonsmokers and female smokers?
Adenocarcinoma
What mutation is commonly seen in lung adenocarcinoma?
k-ras mutation
What defines the Bronchioloalveolar subtype of lung cancer?
It is a subtype of adenocarcinoma. CXR resembles interstitial pneumonia because it grows along the alveolar septa.
Seen in nonsmokers & Eastern Asian women.
What paraneoplastic syndromes are seen with lung cancers?
Hypercalcemia (PTHrP) –> Squamous
ACTH; ADH –> Small cell
Lambert-Eaton –> Small cell
How does bronchial carcinoid appear grossly?
Histologically?
Grossly they are a polyp within the bronchus.
Histologically they are nests of neuroendocrine cells
chromogranin positive
Which lung cancers are neuroendocrine in origin?
Small cell (Kulchitsky cells) Carcinoid
What is a pancoast tumor?
Carcinoma in the apex of the lung:
Horner’s syndrome (cervical chain)
+/- Arm weakness (brachial plexus)
What is SVC syndrome?
Compression of the SVC seen sometimes with lung cancer. Impairs blood drainage from the head, neck, & arms:
Facial plethora (redness)
JVD
Upper extremity edema
Is a medical emergency because it can raise ICP.
What antiplatelet factors are secreted by the endothelium?
PGI2 (prostacyclin)
NO
What is the treatment for status epilepticus?
1) IV lorazepam + load with phenytoin
2) (if still seizing) Phenobarbital
3) (if still seizing) Intubate & give general anesthesia
How are the right and left renal veins different?
The left renal vein drains the kidney, left testicle, and left adrenal. The Right testicular vein drains directly to the IVC. And the Right suprarenal vein also drains directly to the IVC.
How is menopause confirmed?
Serum FSH (>30 U/L)
What is the treatment for thrush in immunocompetent patients?
Nystatin swish & swallow
How many half lives does it take for a drug to be largely gone from the plasma?
5 half lives = ~97% cleared
What are the 3 types of pneumonia?
Lobar
Bronchopneumonia
Interstitial (atypical) pneumonia
What are the organisms that cause atypical pneumonia?
Mycoplasma
Chlamydia
Viruses (CMV, influenza)
Coxiella (Q fever)
What are the common causes of lung abscess?
S. aureus Anaerobes: -Bacteroides -Fusobacterium -Peptostreptococcus
What are the common causes of hypersensitivity pneumonitis?
Moldy hay (farmers) Bird droppings (pigeon breeder's lung)
What is seen in hypersensitivity pneumonitis?
Mixed Type III/IV hypersensitivity reaction –> granulomatous reaction –> can lead to interstitial fibrosis
What is characteristic of transudate effusion?
Exudate?
Chylothorax?
Transudate = low protein content Exudate = high protein content Chylothorax = High TRG content
What causes chylothorax?
Thoracic duct injury from trauma or malignancy.
What causes spontaneous pneumothorax?
Rupture of apical blebs. Usually seen in tall, thin, young males.
What are 1st generation H1 blockers for?
Allergy, motion sickness, sleep aid.
Some examples:
Diphenhydramine
Dimenhydrinate
Chlorpheniramine
What are 2nd generation H1 blockers used for?
Allergy meds. Far less sedating than 1st gen due to less CNS penetration.
Some examples: Loratadine Fexofenadine Desloratadine Cetirizine
What is Theophylline used for?
What is its mechanism?
It is used to cause bronchodilation in asthmatics. It inhibits phosphodiesterase –> ^ cAMP in smooth muscle cells.
It also blocks adenosine’s action (bronchoconstriction) in the lung.
What muscarinic antagonist is first line in COPD?
Tiotropium
long-acting version of Ipratropium
What are the inhaled corticosteroids used in asthma?
Beclomethasone
Futicasone
What is Montelukast?
What is its use?
Montelukast & Zafirlukast are leukotriene receptor antagonists. They are used to treat asthma, especially aspirin-induced asthma.
What is Zileuton?
What is its use?
It is a 5-lipoxygenase pathway inhibitor (blocks conversion of arachidonic acid to leukotrienes). It is used to treat asthma.
What is N-acetylcysteine used for?
1) Mucolytic - loosens mucous plugs in CF patients
2) Donates sulfhydryl groups to treat acetaminophen OD
What is Bosentan?
What is it used for?
It is an endothelin-1 receptor antagonist used to treat pulmonary hypertension.
What is Dextromethorphan?
What is it used for?
It is a synthetic codeine analog used as an antitussive.
What is phenylephrine?
What is it used for?
Phenylephrine & pseudoephedrine are alpha-agonists used as OTC nasal decongestants.
They are stimulants & can cause anxiety or hypertension with toxicity.
What antiplatelet factors are secreted by the endothelium?
PGI2 (prostacyclin)
NO
What is the treatment for status epilepticus?
1) IV lorazepam + load with phenytoin
2) (if still seizing) Phenobarbital
3) (if still seizing) Intubate & give general anesthesia
How are the right and left renal veins different?
The left renal vein drains the kidney, left testicle, and left adrenal. The Right testicular vein drains directly to the IVC. And the Right suprarenal vein also drains directly to the IVC.
How is menopause confirmed?
Serum FSH (>30 U/L)
What is the treatment for thrush in immunocompetent patients?
Nystatin swish & swallow
How many half lives does it take for a drug to be largely gone from the plasma?
5 half lives = ~97% cleared
What are the 3 types of pneumonia?
Lobar
Bronchopneumonia
Interstitial (atypical) pneumonia
What are the organisms that cause atypical pneumonia?
Mycoplasma
Chlamydia
Viruses (CMV, influenza)
Coxiella (Q fever)
What are the common causes of lung abscess?
S. aureus Anaerobes: -Bacteroides -Fusobacterium -Peptostreptococcus
What are the common causes of hypersensitivity pneumonitis?
Moldy hay (farmers) Bird droppings (pigeon breeder's lung)
What is seen in hypersensitivity pneumonitis?
Mixed Type III/IV hypersensitivity reaction –> granulomatous reaction –> can lead to interstitial fibrosis
What is characteristic of transudate effusion?
Exudate?
Chylothorax?
Transudate = low protein content Exudate = high protein content Chylothorax = High TRG content
What causes chylothorax?
Thoracic duct injury from trauma or malignancy.
What causes spontaneous pneumothorax?
Rupture of apical blebs. Usually seen in tall, thin, young males.
What are 1st generation H1 blockers for?
Allergy, motion sickness, sleep aid.
Some examples:
Diphenhydramine
Dimenhydrinate
Chlorpheniramine
What are 2nd generation H1 blockers used for?
Allergy meds. Far less sedating than 1st gen due to less CNS penetration.
Some examples: Loratadine Fexofenadine Desloratadine Cetirizine
What is Theophylline used for?
What is its mechanism?
It is used to cause bronchodilation in asthmatics. It inhibits phosphodiesterase –> ^ cAMP in smooth muscle cells.
It also blocks adenosine’s action (bronchoconstriction) in the lung.
What muscarinic antagonist is first line in COPD?
Tiotropium
long-acting version of Ipratropium
What are the inhaled corticosteroids used in asthma?
Beclomethasone
Futicasone
What is Montelukast?
What is its use?
Montelukast & Zafirlukast are leukotriene receptor antagonists. They are used to treat asthma, especially aspirin-induced asthma.
What is Zileuton?
What is its use?
It is a 5-lipoxygenase pathway inhibitor (blocks conversion of arachidonic acid to leukotrienes). It is used to treat asthma.
What is N-acetylcysteine used for?
1) Mucolytic - loosens mucous plugs in CF patients
2) Donates sulfhydryl groups to treat acetaminophen OD
What is Bosentan?
What is it used for?
It is an endothelin-1 receptor antagonist used to treat pulmonary hypertension.
What is Dextromethorphan?
What is it used for?
It is a synthetic codeine analog used as an antitussive.
What is phenylephrine?
What is it used for?
Phenylephrine & pseudoephedrine are alpha-agonists used as OTC nasal decongestants.
They are stimulants & can cause anxiety or hypertension with toxicity.
What are the stages of fetal kidney development?
Pronephros = week 4; degenerates
Mesonephros = interim kidney during 1st trimester; forms Wolffian ducts in male
Metanephros = Permanent; nephrogenesis runs from 5th week to 32-36 weeks.
What are the components of the metanephros?
What do they give rise to?
1) Ureteric bud: forms collecting system (collecting ducts, calyces, pelvises, ureters
2) Metanephric mesenchyme: forms glomerulus through DCT. Induced by interaction with the ureteric bud.
What is the last portion of the fetal kidney to canalize?
The ureteropelvic junction. This is why it is the most common site of obstruction (hydronephrosis) in the fetus.
What is Potter’s syndrome?
Oligohydramnios –> limb/facial deformities, pulmonary hypoplasia, death in-utero
Caused by: Bilateral renal agenesis, ARPKD
What is seen with horseshoe kidney?
Inferior poles are fused –> get caught on IMA & remain low in abdomen.
It is associated with Turner syndrome.
What causes dysplastic kidney?
Abnormal interaction between ureteric bud and metanephric mesenchyme –> nonfunctional kidney composed of cysts and connective tissue. Usually unilateral, NON-inherited.
What is the course of the ureters?
“Water under the bridge”
They pass under the uterine artery, ductus deferens, & gonadal artery/vein.
What is the body composition of water?
60-40-20 rule:
60% water
40% is intracellular
20% is extracellular
1/4 of that extracellular fluid is plasma, 3/4 is interstitial.
What is the glomerular filtration barrier composed of?
Fenestrated capillary endothelium
Basement membrane with heparan sulfate (neg. charge)
Epithelial barrier of podocyte foot processes
What is the equation for renal clearance of a substance?
CL = UV/P
U = Urine concentration of the solute V = Urine flow rate P = Plasma concentration of the solute
If CL > GFR –> net tubular secretion of the solute
If CL < GFR –> net tubular reabsorption of the solute
What substance can be used to calculate GFR?
RPF?
Inulin = freely filtered, not reabsorbed/secreted –> GFR
(Creatinine clearance approximates it but slightly overestimates)
PAH = filtered & secreted completeley –> effective RPF (ERPF)
(Underestimates true RPF by ~10%)
By calculating the clearance of these substances (CL = UV/P), you can get the GFR & RPF.
What is the equation for renal blood flow?
RBF = RPF/(1 - HCT)
What is the equation for filtration fraction?
What is a normal FF?
FF = GFR/RPF
Normal = 20%
What are the relative bloodflows to organs under resting conditions?
“Having Sex Brings Many Kids Later”
Heart = 250 mL/min = 5% Skin = 500 mL/min = 10% Brain = 750 mL/min = 15% Muscle = 1000 mL/min = 20% Kidney = 1250 mL/min = 25% Liver = 1500 mL/min = 30%
What are the effects of NSAIDs on the kidney?
ACE inhibitors?
NSAIDs constrict afferent arteriole (inhibit prostaglandins that normally dilate it)
ACE inhibitors dilate efferent arteriole (AT-II preferentially constricts efferent arteriole)
How is the reabsorption/secretion of a substance (x) calculated?
Filtered load = GFRP[x]
Excreted load = VU[x]
Reabsorption rate = filtered - excreted
Secretion rate = excreted - filtered
At what serum glucose does glucose appear in the urine?
> 160 mg/dL –> glucosuria begins
>350 mg/dL –> all transporters saturated
What is the effect of PTH on the nephron?
Proximal tubule:
PTH inhibits Na+/phosphate cotransport –> phosphate excretion
Distal tubule:
PTH increases Ca2+/Na+ exchange –> Ca2+ reabsorption
What is the effect of Angiotensin II in the nephron?
Proximal tubule:
Stimulates Na+/H+ exchange –> ^ Na+/H2O/HCO3- reabsorption
Also causes efferent arteriole constriction –> ^ FF
What is reabsorbed in the Proximal tubule?
In order of reabsorption rate: Glucose Amino acids HCO3- Phosphate Na+ (65-80%) K+ Cl- Urea
Why does silicosis increase susceptibility to MTB infection?
Macrophage phagolysosomes are disrupted.
What occurs in SMA syndrome?
The angle of the superior mesenteric artery and the aorta decreases, compressing & obstructing the transverse portion of the duodenum. This will cause symptoms of small bowel obstruction.
What causes SMA syndrome?
Any very catabolic state (weight loss, burns, long bedrest) leading to diminished mesenteric fat
Low body weight
Severe lordosis
Surgical correction of scoliosis
What are the two types of MG exacerbation?
Myasthenic crisis:
Too low of AChE inhibitor dose
Responds to edrophonium (short-acting AChE inhibitor)
Cholinergic crisis:
Too high of AChE inhibitor dose (muscle cells depolarized too often & can’t recover)
Does not respond to edrophonium
What steps in collagen synthesis occur extracellularly?
Cleavage of N & C terminal peptides
Spontaneous assembly of fibrils
Covalent crosslinking by lysyl oxidase
What does glycerol kinase do?
Where is it located?
It catalyzes Glycerol (from beta oxidation) –> DHAP
This allows glycerol to enter glycolysis or gluconeogenesis.
It is specific to the liver.
What are the symptoms of lead poisoning?
Colicky abdominal pain (lead colic), constipation, headaches
Lead line (blue pigment) at the gum-tooth line
Wrist/foot drop due to peripheral neuropathy
Microcytic hypochromic anemia with basophilic stippling
What is used to determine the proliferation rate of cancer cells?
Ki-67 fraction
Ki-67 is an antigen that is only present on actively dividing cells. The closer to 100%, the more cells are actively dividing.
What is Cromylin sodium?
What is it used for?
It inhibits mast cell degranulation.
It is used for asthma prophylaxis.
What are the initiator caspases?
Executioner caspases?
Initiator caspases = 8 & 10
Executioner caspases = 3 & 6
What is reabsorbed in the thick ascending limb?
Na+/K+/2Cl- (via symporter)
Mg2+/Ca2+ (paracellular, pushed electrically by K+ backleak into tubule)
What is reabsorbed in the DCT?
Na+/Cl- (symporter)
Ca2+ (antiporter with Na+ is at basolateral membrane & channels are at apical membrane)
What is reabsorbed in the Collecting tubules?
Reabsorb Na+ in exchange for K+ & H+ (Aldosterone)
Water is reabsorbed via aquaporins (ADH)
How is total body water measured?
Extracellular fluid?
Plasma volume?
TBW - tritiated water
ECF - inulin
Plasma - radiolabeled albumin
What cell types are found in the nephron’s collecting duct?
What are their purposes?
Principal cells:
Reabsorb Na+ (Ald –> ENaC synthesis)
Reabsorb H2O (ADH –> aquaporin insertion)
Secrete K+
Intercalated cells:
Secrete H+ (aldosterone stimulated ATPase)
What are the stimulators of renin?
Decreased BP
Decreased NaCl delivery to DCT (sensed by macula densa cells)
B1 adrenergic receptor simulation
Secreted by JG cells
What are the effects of Angiotensin II?
AT-1 receptors –> systemic vasoconstriction
Constricts efferent arteriole (^ FF)
Aldosterone & ADH secretion
Increases activity of PCT Na+/H+ antiporter
Stimulates thirst in hypothalamus
Where is EPO synthesized?
EPO is made in the peritubular capillary cells of the renal cortex in response to hypoxia.
Where exactly is 25-OH-Vitamin D activated to Calcitriol?
Proximal tubule cells
What can cause potassium to shift out of cells?
DO LAB:
Digitalis Osmolarity ^ Lysis Acidosis Beta blockers
Whereas INsulin shifts K+ INto cells
What is seen with hypomagnesemia?
Decreased DTR’s
Lethargy
Bradycardia & hypotension
Hypocalcemia
How can a simple vs. mixed metabolic acidosis be determined?
Calculate the expected PCO2 & see if the true PCO2 is adequately compensating (+/- 2).
Expected PCO2 = 1.5*(HCO3-) + 8
If the true PCO2 is within 2 either way –> simple
If it is not within 2 –> mixed acid-base disorder
What causes contraction alkalosis?
Loss of blood volume –> Renin, AT, Ald system
ATII:
^Na+/H+ exchange in PCT
^HCO3- reabsorption (due to ^H+ available in the lumen)
Ald:
^ H+ ATPase activity –> H+ secretion
How is an anion gap calculated?
Na - (Cl + HCO3)
Normal = 8-12
What can cause an increased anion gap metabolic acidosis?
MUDPILES:
Methanol Uremia DKA Propylene glycol INH or Iron tablets Lactic acidosis Ethylene glycol Salicylates (late)
What can cause a non-anion gap metabolic acidosis?
HARDASS:
Hyperalimentation (overeating, too much TPN) Addison's Renal tubular acidosis Diarrhea Acetazolamide Spironolactone Saline infusion
What can cause a metabolic alkalosis?
Loop diuretics
Vomiting
Antacids
Hyperaldosteronism
What are the causes of the renal tubular acidoses?
Type 1 = Collecting duct cannot excrete H+ (distal)
Type 2 = PCT cannot reabsorb HCO3 (proximal)
Type 3 = Hypoaldosteronism or collecting duct not responsive to it –> hyperkalemia –> impaired ammoniagenesis –> urine cannot buffer titratable acids
What are the risks of the renal tubular acidoses?
“Stones, bones, and low aldosterones”
Type 1 –> Nephrolithiasis
Type 2 –> Hypophosphatemic rickets
Type 3 –> hyperkalemic metabolic acidosis
What are the casts & their significance?
RBC casts WBC casts Fatty casts (oval fat bodies) = nephrotic syndrome Granular (muddy brown) casts = ATN Waxy casts = Chronic/advanced disease Hyaline casts = nonspecific
What is seen with nephrotic syndrome?
PALE:
Proteinuria (> 3.5g/day)
Albumin low
Lipidemia/lipiduria
Edema
ATIII loss –> thromboembolism
Ig loss –> infection
What is seen on microscopy with FSGS?
LM - focal (< half) & segmental sclerosis & hyalinosis
EM - effacement of foot processes
What is seen on microscopy with Membranous nephropathy?
LM - diffuse GMB thickening (“membranous”)
EM - “spike & dome” appearance with subepithelial deposits
What is seen on microscopy with Minimal Change Disease?
LM - normal glomeruli
EM - effacement of foot processes
What is seen on microscopy with Membranoproliferative Glomerulonephritis?
Type I - subendothelial immune complex deposits with “tram track” appearance; granular IF pattern
Type II - intramembranous immune complex “dense deposits”
What is seen on microscopy with diabetic nephropathy?
LM - mesangial expansion, GBM thickening; Kimmelstiel-Wilson nodules`
What is seen on microscopy with Post-infectious glomerulonephritis?
LM - PMN’s, lump-bumpy appearance
EM - subepithelial humps of immune complexes
IF - granular deposits along GBM
What is seen on microscopy with RPGN?
Crescents
Composed of:
Fibrin
Plasma proteins
Macrophages
IF - can be linear (type 1), granular (type 2), or pauci-immune (type 3)
What is seen on microscopy with diffuse proliferative glomerulonephritis?
LM - “wire looping” of capillaries
EM - subedothelial & sometimes intramembranous immune complexes
IF - granular
What is seen on microscopy with Berger’s disease?
LM - mesangial proliferation
EM - mesangial immune complex deposits
IF - IgA-based immune complex deposits in mesangium
What is associated with FSGS?
Most common nephrotic syndrome in Hispanic & Blacks HIV --> wall collapse variant Heroin Sickle cell Interferon treatment
What is associated with minimal change disease?
Most common nephrotic syndrome in children
Selective loss of albumin (loss of GBM polyanions)
Responds to corticosteroids
Hodgkin’s lymphoma
What is associated with membranoproliferative GM?
Type I - HBV, HCV
Type II - C3 nephritic factor (Ig that stabilizes C3 convertase leading to overactivation of complement)
Which nephrotic syndrome causes are due to immune complex deposits?
Anything with “membrano-“ in the name:
Membranous = subepithelial IC deposits
MPGN Type I = subendothelial IC deposits
MPGN Type II = intramembranous IC deposits
What is membranous nephropathy associated with?
Found in white adults
SLE’s nephrotic presentation
Drugs, infections, solid tumors (caused by in-situ IC deposition)
What is seen with nephritic syndrome?
PHAROH:
Proteinuria (<3.5 g/day) Hematuria & RBC casts Azotemia RBC casts Oliguria Hypertension
What are the causes of RPGN?
Type I = Goodpasture’s syndrome (Ig’s against kidney & lung BM)
Type II = Any of the other nephritic syndromes but worse
Type III = pauci-immune (GPA, Churg-Strauss, MP)
What is associated with Diffuse Proliferative GM?
It is the nephritic presentation of SLE or MPGN. It is the most common cause of death in SLE.
How does Berger’s disease present?
aka IgA nephropathy
Associated with Henoch-Schonlein purpura
It is the most common nephropathy.
It presents in childhood with intermittent gross or microscopic hematuria (following URI or gastroenteritis).
What causes Alport syndrome?
An X-linked mutation in Type-IV collagen –> triad of:
Nephritic syndrome
Deafness
Ocular problems
What are the 4 types of kidney stones?
Calcium (oxalate/phosphate)
Ammonium-magnesium-phosphate (struvite)
Uric acid
Cystine
Which kidney stones precipitate in acidic urine?
Alkaline urine?
Which stone is radiolucent?
Acidic = Cystine, Uric acid & Calcium oxalate Basic = Calcium phosphate & Struvite
Uric acid stones are radiolucent. All others are radiopaque.
What causes struvite stones?
aka ammonium-magnesium-phosphate stones
Caused by urease positive UTI’s (Proteus, Klebsiella, Staph)
What kidney stones for staghorn calculi?
Struvite & Cystine stones
How does renal (clear) cell carcinoma present clinically?
Often silent for a long time. Symptoms: Triad - hematuria, flank pain, palpable mass Paraneoplastic syndromes (EPO, ACTH, PTHrp) Left-sided varicocele
What mutation is present in Von Hippel-Lindau disease?
What is seen?
VHL gene deletion (chrom. 3) –> Constitutive HIF (angiogenic TF)
Presentation:
Bilateral renal cell carcinoma
Hemangioblastomas of retina/cerebellum/medulla
What is Wilms’ tumor associated with?
aka nephroblastoma
Most common renal cancer in children:
Deletion of WT2 tumor suppressor gene on chromosome 11
May be part of:
Beckwith-Wiedemann syndrome
WAGR complex (Wilms’, Aniridia, GU malformation, Retardation)
What are the risk factors for transitional cell carcinoma?
cancer in your P SAC:
Phenacetin
Smoking
Aniline dyes
Cyclophosphamide
What are the risk factos for squamous cell carcinoma of the bladder?
Must have squamous metaplasia first.
- Schistosoma hematobium (Middle-Eastern male)
- Chronic cystitis (older woman)
- Longstanding nephrolithiasis
What are the common causes of drug-induced interstitial nephritis?
Diuretics Penicillins Sulfa drugs Rifampin NSAIDs
What is seen with acute interstitial nephritis?
AKI Fever Rash Hematuria Pyuria (eosinophils)
What can cause renal papillary necrosis?
Diabetes Severe acute pyelonephritis Chronic phenacetin/Aspirin/Acetaminophen use Sickle cell anemia & trait Severe interstitial nephritis
What are the phases of ATN & their risks?
1) Inciting event (ischemic or nephrotoxic)
2) Maintenance phase - 1-3 weeks; oliguria; risk of hyperkalemia
3) Recovery phase - polyuria; BUN & Cr return to baseline; risk of hypokalemia
What is the BUN/Cr ratio in the various forms of AKI?
Prerenal: >20
Intrinsic renal: 15, chronic <15
What are the most common causes of ATN?
Aminoglycosides Heavy metals Myoglobinuria Ethylene glycol Radiocontrast dye Urate (tumor lysis syndrome)
What is seen with chronic renal failure?
Uremia Na+/H2O retention --> HTN Hyperkalemic metabolic acidosis Anemia Renal osteodystrophy Dyslipidemia
What is seen with uremia?
Nausea & anorexia Pericarditis Asterixis Encephalopathy Platelet dysfunction
What causes renal osteodystrophy?
CKD –> hyperphosphatemia alongside reduced Vit. D activation –> Secondary hyperparathyroidism –> subperiosteal thinning of bones & metastatic calcification
What causes ADPKD?
What is it associated with?
Autosomal Dominant mutation in PKD1 or PKD2
Associated with: CKD HTN (^ renin production) Berry aneurysms Mitral valve prolapse Benign hepatic cysts
What is seen in ARPKD?
Potter's syndrome Congenital hepatic fibrosis HTN Portal HTN Progressive renal insufficiency
What toxicities are seen with loop diuretics?
OH DANG
Ototoxicity Hypokalemia/Hypocalcemia Dehydration Allergy (sulfa) Nephritis (interstitial) Gout
What is the mechanism of the diuretic classes? Acetazolamide Loop diuretics Thiazides Spironolactone Triamterine/Amiloride
Acetazolamide = carbonic anhydrase inhibitor Loop diuretics (furosemide, ethacrynic acid) = Na+/K+/2Cl- inhib. Thiazides = DCT NaCl transporter inhibitor Spironolactone = Aldosterone antagonists Triamterine/Amiloride = block cortical collecting duct ENaC's
What toxicities are seen with thiazide diuretics?
Hypokalemic metabolic alkalosis Sulfa reaction hyperGLUC: Glycemia Lipidemia Uricemia Calcemia
What are the potassium sparing diuretics?
Spironolactone
Eplerenone
Triamterine
Amiloride
What toxicities are seen with ACE Inhibitors?
Captopril’s CATCHH
Cough (bradykinin; not seen with ARB)
Angioedema (bradykinin; not seen with ARB)
Teratogen (fetal renal malformations)
Creatinine ^ (decreased GFR due to efferent art. dilation)
Hyperkalemia
Hypotension
What do integrins bind in the ECM?
Collagen
Fibronectin
Laminin
How is fructose dealt with in patients that have essential fructosuria?
Fructose is converted to Fructose-6-P by hexokinase. This can then participate in glycolysis or glycogenesis. This is a minor pathway in normal individuals but becomes important in the setting of fructokinase deficiency.
Where should thoracentesis be performed?
Midclavicular = 5th-7th rib Midaxillary = 7th-9th rib Paravertebral = 9th-11th rib
This is the location where there is pleura but no lung. It should always be performed above a rib so as not to damage the van driving under the rib.
What are found in the granules of platelets?
Dense granules: ADP, Ca2+
alpha-granules: vWF, fibrinogen
What are the relative abundancies of the various leukocytes?
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
What coagulation factors require Vitamin K?
II, VII, IX, X, C, S
What is the mechanism of warfarin?
Inhibits epoxide reductase.
Normall reduces Vit. K so that it can act as a cofactor in factors II, VII, IX, X, C, S
What can cause decrease in the ESR?
Polycythemia Sickle cell CHF Microcytosis Hypofibrinogenemia
What can cause spherocytes on a peripheral blood smear?
Hereditary spherocytosis
Autoimmune hemolysis
What can cause target cells on a peripheral blood smear?
HALT
HbC disease
Asplenia
Liver disease
Thalassemia
What can cause Howell-Jolly bodies on peripheral blood smear?
Asplenia
Functional asplenia
Naphthalene ingestion (mothballs)
What are the microcytic hypochromic anemias?
MCV < 80 Iron deficiency Anemia of chronic disease (late) Thalassemias Lead poisoning Sideroblastic anemias
What is seen with Plummer-Vinson syndrome?
Plummer-Vinson triad:
Iron-deficiency anemia
Esophageal webs
Atrophic glossitis
What is seen in alpha-thalassemia?
4 gene deletion –> Hb Barts –> hydrops fetalis (death in-utero)
3 gene deletion –> HbH disease anemia
1-2 gene deletion –> asymptomatic
What causes alpha-thalassemia?
Deletion of the alpha-globin genes.
cis-deletion in Asians
trans-deletion in Africans
cis-deletion is associated with higher rates of hydrops fetalis in offspring.
What is seen in beta-thalassemia?
Thalassemia minor (heterozygote):
Asymptomatic
Dx confirmed by HbA2 > 3.5%
Thalassemia major (homozygote):
Severe anemia requiring transfusions (hemochromatosis)
Marrow expansion –> HSM, crew cut x-ray, chipmunk facies
^HbF & HbA2
Parvovirus infection –> aplastic crisis
What is affected by lead poisoning?
What are the symptoms?
ALA dehydratase & Ferrochelatase are inhibited (heme synth)
Symptoms: LEEAADD: Lead lines on gingiva & metaphyses of long bones Encephalopathy Erythrocyte stippling Anemia (sideroblastic) Abdominal colic Drops (wrist & foot) Dimercaprol & EDTA first line
What causes Sideroblastic anemia?
Defects in heme synthesis:
Hereditary - X-linked defect in ALA Synthase
Acquired - EtOH, lead poisoning, INH (B6 def.)
How can Folate vs. B12 deficient megaloblastic anemia be differentiated?
B12 deficiency:
^Methylmalonic acid
Subacute combined degeneration
What are the causes of macrocytic anemia?
Megaloblastic:
B12 def.
Folate def.
Orotic aciduria
Non-megaloblastic:
Alcoholism
Liver disease
Reticulocytosis
What are the lab findings in extravascular vs. intravascular hemolysis?
Intravascular: ^LDH, depleted haptoglobin, Hb in urine
Extravascular: ^LDH, ^unconjugated bilirubin
What causes anemia of chronic disease?
What do iron studies show?
Chronic inflammation –> ^Hepcidin –> sequestration of iron in intestinal mucosa & macrophages –> normocytic anemia that progresses to microcytic.
Decreased iron, decreased TIBC, increased ferritin
What can cause aplastic anemia?
Drugs (chloramphenicol, alkylating agents, antimetabolites)
Viruses (Parvovirus, EBV, HIV, HCV)
Fanconi’s anemia
What is the formula for corrected reticulocyte count?
Corrected reticulocytes = (Absolute reticulocytes)*(HCT/45)
If corrected > 3% –> adequate response
If < 3% –> issue with the bone marrow
What are the intravascular hemolytic anemias?
G6PD deficiency Paroxysmal nocturnal hemoglobinuria Cold agglutinins Microangiopathic anemia Macroangiopathic anemia Infections (malaria, Babesia)
What are the extravascular hemolytic anemias?
Hereditary spherocytosis G6PD deficiency Pyruvate kinase deficiency Sickle cell anemia Warm agglutinins
What causes hereditary spherocytosis?
What is seen?
Defect in RBC cytoskeletal anchoring proteins (ankyrin, spectrin) –> small pieces of membrane removed by splenic macs
Symptoms: Splenomegaly Aplastic crisis (Parvovirus) Small, round RBC's with no central pallor ^MCHC, ^ RDW Positive osmotic fragility test
What is seen on a blood smear of a G6PD patient?
Heinz bodies
Bite cells
How does pyruvate kinase deficiency present?
(AR) Hemolytic anemia in a newborn.
Decreased ATP causes rigid RBC’s
What causes HbC disease?
What is seen?
AR mutation of beta chain. Glutamic acid –> LyCine at residue 6.
Symptoms:
Mild extravascular hemolytic anemia
HbC crystals on blood smear (rectangular)
What causes PNH?
What is seen?
Impaired formation of GPI anchors or DAF deficiency. It is an ACQUIRED mutation in a HSC line.
Symptoms: Pancytopenia Numerous DVT's; hepatic/portal/cerebral vein thromboses Hemolytic anemia Flow cytometry - CD55/59 negative RBC's 10% develop AML
What is the treatment for PNH?
Eculizumab - C5 complement inhibitor
What causes sickle cell anemia?
HbS point mutation in beta chain
Glutamic acid –> Valine at position 6.
Low O2, dehydration, or acidosis –> polymerization of deoxygenated HbS –> Sickling
What is seen in sickle cell trait?
Resistance to malaria
Microinfarctions in kidney medulla –> eventual inability to concentrate urine
What complications are seen with sickle cell anemia?
Salmonella osteomyelitis Autosplenectomy --> Infection with SHiNE SKiS (death in kids) Painful crises: --Dactylitis --Acute chest syndrome (death in adults) --Avascular necrosis Aplastic crisis (Parvovirus) Renal papillary necrosis
What is the treatment for sickle cell anemia?
Hydroxyurea –> HbF
Bone marrow transplant
What can trigger candida vaginitis?
Antibiotic use! Contraceptives Systemic corticosteroids Diabetes Immunosuppression
What are the important glucose transporters and their locations?
GLUT-1 = insulin-independent; RBC's, brain GLUT-2 = bidirectional; Beta cells, liver, kidney small intestine GLUT-4 = insulin-dependent; Adipocytes, muscle cells
What cancers are seen in Li-Fraumeni syndrome?
Early-onset cancers: Breast Brain Adrenal cortex Sarcomas Leukemias
What is the epithelial cell type along the female reproductive tract?
Vagina = nonkeratinized stratified squamous
Ectocervix = stratified squamous
Endocervix = simple columnar
Uterus = simple columnar; pseudostratified glands
Fallopian tube = ciliated columnar
Ovary = simple cuboidal
How can tumor lysis syndrome be avoided?
It is due to ^^uric acid following rapid killing of tumor cells.
Methods:
Hydration
Urine alkalinization
Allopurinol
What are the adverse effects of methotrexate?
Stomatitis
Hepatotoxicity (hepatitis, fibrosis, cirrhosis)
Myelosuppression
What can cause autoimmune hemolytic anemia?
Warm agglutinins (IgG):
SLE
CLL
Drugs (methyldopa)
Cold agglutinins (IgM):
CLL
Mycoplasma pneumoniae
Mononucleosis
What normal process can increase TIBC?
Pregnancy or OCP use
What substrates are used to produce heme?
Glycine
Succinyl-CoA
Iron (Fe2+)
**B6 is required for the first step
Where in the cell does heme synthesis occur?
First & last step in the mitochondria. The middle is in the cytosol.
What accumulates in the blood following lead poisoning?
ALA (aminolevulonic acid)
Protoporphyrin
What are the symptoms of Acute Intermittent Porphyria?
5 P’s:
Painful abdomen
Port-wine colored urine (after it stands a while)
Polyneuropathy
Psychological disturbances
Precipitated by drugs (CYP450 inducers –> ^Heme production)
What causes Acute Intermittent Porphyria?
What accumulates?
Caused by Porphobilinogen deaminase deficiency
Porphobilinogen, ALA, & uroporphyrin accumulate
What is the treatment for acute intermittent porphyria?
Heme & Glucose –> both inhibit ALA synthase
What causes Porphyria cutanea tarda?
What accumulates?
What is seen?
Uroporphyrinogen decarboxylase deficiency
Uroporphyrin builds up
Symptoms:
Blistering cutaneous photosensitivity later on in life (cutanea tarda)
Tea colored urine
*The most common porphyria
What are the qualitative platelet disorders & their causes?
Bernard-Soulier syndrome = GPIb defect (adhesion)
Glanzmann’s thrombasthenia = GP IIb/IIIa defect (aggregation)
*BS = big suckers (PLT’s turned over faster –> low PLT count & larger platelets)
What is the cause of ITP?
Autoimmune Ab’s against GPIIb/IIIa –> splenic consumption of platelets
Tx: Steroids, IVIg, splenectomy (refractory)
What is the cause of TTP & HUS?
TTP:
ADAMTS13 deficiency (acquired via autoimmunity or congenital)
–> circulating ^vWF multimers –> ^PLT aggregation & thrombosis
HUS:
Verotoxin damage of endothelium –> PLT aggregation & thrombosis
What is seen with TTP-HUS?
Altered mental status Acute kidney injury Thrombocytopenia Microangiopathic hemolytic anemia Fever
What is seen in von Willebrand’s disease?
What is the treatment?
Autosomal dominant deficiency in vWF:
^bleeding time & ^PTT
Abnormal ristocetin assay
Tx: Desmopressin (DDAVP) –> ^vWF release from W-P bodies
What are the causes of DIC?
“STOP Making New Thrombi Stupid”
Sepsis (gram-) Trauma Obstetric complications (tissue thromboplastin in amniotic fluid) Pancreatitis (acute) Malignancy Nephrotic syndrome Transfusion Snakebites (rattlesnake)
What is the most common inherited bleeding disorder?
Hypercoagulable disorder?
Bleeding - vWD
Hypercoagulable - Factor V Leiden (especially whites)
What are the inherited thrombotic syndromes?
Factor V Leiden Prothrombin mutation (3' UTR mut. --> ^^production) Antithrombin deficiency (normalizes with heparin) Protein C or S deficiency (^coumadin-induced-necrosis)
How can CML be differentiated from a leukemoid reaction?
CML: Myeloid:Erythroid > 10:1 Alkaline phosphatase negative ^Basophils t[9;22]
What are the symptoms of Hodgkin’s Lymphoma?
Localized group of LAD
“B” symptoms (fever, night sweats, weight loss)
Reed-Sternberg cells
Diagnosis?
“Owl’s eye” nuclei = mirror image bi-lobed or bi-nucleated with nucleolus. CD15+ & CD30+
Usually surrounded by reactive lymphocytes.
Hodgkin’s Lymphoma
What types of Hodgkin’s lymphoma have a better/worse prognosis?
Lymphocyte rich –> better prognosis
Lymphocyte depleted –> worse prognosis
Popcorn cells
Diagnosis?
Nodular lymphocyte predominant hodgkin’s lymphoma (NLPHL)
Different from nodular sclerosing type (most commen; women = men)
What type of lymphoma has a bimodal age distribution?
Hodgkin’s = young adulthood & then > 55y
Non-hodgkin’s = 20-40y
Lacunar cells
Diagnosis?
Reid-Sternberg cells that appear to be in a lake because there is a space around them.
Nodular sclerosing hodgkin’s lymphoma
How can bands be distinguished by flow cytometry?
They have decreased CD16 (FcR) on their surface.
What are the non-Hodgkin’s lymphomas?
B-cell: Burkitt's Diffuse large B-cell Mantle cell Follicular
T-cell:
Adult T-cell
Mycosis fungoides/Sezary syndrome
t(8;14)
Diagnosis?
Burkitt’s lymphoma
c-myc activation
“Starry sky” appearance
Burkitt’s lymphoma
Sheets of basophilic B-cells with interspersed macrophages.
What mutation is seen in mantle cell lymphoma?
What cell-marker is seen?
t(11;14) - Cyclin D1 translocated to Ig heavy chain location
CD5+
t(14;18)
Diagnosis?
Follicular lymphoma & DLCL
Translocation of Ig heavy chain and bcl-2.
How does adult T-cell lymphoma present?
Rash & lytic bone lesions
Caused by HTLV-1 (seen in Japan, Africa, Caribbean)
What can cause marginal zone lymphoma?
Marginal zone only seen in chronic inflammatory conditions:
MALToma
Hashimoto’s
Sjogren’s
T-cells with Cerebriform nuclei
Diagnosis?
Sezary syndrome (systemic mycosis fungoides)
Mycosis fungoides –> Pautrier microabscesses in skin
What are the symptoms of multiple myeloma?
CRAB: hyperCalcemia Renal insufficiency Anemia Bone lytic lesions --> back pain
What is seen on labs with multiple myeloma?
What are the risks?
Punched out lytic bone lesions on x-ray
M-spike on electrophoresis (IgG > IgA)
Bence-Jones protein in urine (Ig light chain)
Rouleaux formation
Many plasma cells with “clock face” chromatin
Risks:
Susceptibility to infection (most common COD)
Primary amyloidosis (AL)
What is seen with Waldenstrom’s macroglobulinemia?
M spike of IgM (macro) –> hyperviscosity symptoms only
What is asymptomatic multiple myeloma?
Monoclonal Gammopathy of Undetermined Significance (MGUS)
1% chance per year of –> MM
What are the symptoms of leukemia in general?
Marrow failure:
Anemia (RBC’s)
Infection (WBC’s)
Hemorrhage (PLT’s)
What type of leukemia is seen in kids?
ALL
What is the cell marker of ALL?
Acute Lymphoblastic Leukemia/Lymphoma
All ALL are TdT+
Pre-B = CD10/19/20+ Pre-T = CD1/2/5+
What is seen on a CLL/SLL peripheral blood smear?
How does it present?
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Smudge cells on peripheral smear
Asymptomatic or autoimmune hemolytic anemia
What cell marker is used for hair cell leukemia?
TRAP (tartrate-resistant acid phosphatase)
“TRAP the hairy animal”
It remains TRAPPED in red pulp (spleen) & bone marrow –> no LAD
What is the treatment for hairy cell leukemia?
Cladribine
It is a purine analog that inhibits ADA.
How does APL present?
What is seen on peripheral smear?
APL (M3 subtype of AML) often presents with DIC because Auer rods (present on peripheral smear; crystallized MPO) can induce DIC.
t(15;17)
Diagnosis?
M3 subtype of AML = APL
Treat with ATRA
t(9;22)
Diagnosis?
Chronic Myelogenous Leukemia (CML)
t(9;22) = bcr-abl fusion
How does CML present?
How is it treated?
^Basophils, neutrophils, metamyelocytes
Splenomegaly
May transform into AML > ALL
Responds to Imatinib
What leukemias are seen at increased rates in Down syndrome?
Before 5y –> Acute megakaryoblastic leukemia
After 5y –> ALL
What is seen in Langerhans histiocytosis?
Proliferation of dendritic cells –> lytic bone lesions & skin rash
Birbeck granules (tennis rackets)
S-100+ & CD1a+
How does polycythemia vera present?
^RBC’s, ^WBC’s, ^PLT’s
DVT’s
#1 cause of bud-chiari
Itching after a hot shower (^mast cells)
Dacrocyte
Diagnosis?
Dacrocyte = teardrop cell –> Myelofibrosis
“The marrow is crying because it’s fibrosed”
It is its own chronic myeloproliferative disorder and can also be seen late in polycythemia vera.
What can cause inappropriate production of EPO?
Renal cell carcinoma Wilms' tumor Renal cysts HCC Hydronephrosis
What is the mechanism of heparin?
Cofactor for Antithrombin –> inactivates Xa & IIa
What is the mechanism of HIT?
Heparin-induced thrombocytopenia
IgG Ab’s against Hepatin-Platelet factor 4 –> Ab-Heparin-PF4 complex activates platelets –> thrombosis & thrombocytopenia
What is Lepirudin?
Lepirudin & Bivalirudin are thrombin inhibitors used as an alternative to heparin following HIT
What is the treatment for thrombolytic overdose?
Aminocaproic acid
What are the thrombolytic drugs?
What is their mechanism
When are they contraindicated?
Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)
They cause activation of plasminogen –> plasmin –> cleaves thrombin & fibrin clots & fibrinogen
Contraindicated in active bleeding, Hx of intracranial bleeding, severe HTN.
What is the mechanism of aspirin?
What are its toxicities?
Irreversible COX-1 & COX-2 inhibitor. Endothelial cells can resynthesize COX-2 –> PGI2. Platelets cannot resynthesize COX-1 –> decreased TXA2.
Toxicity:
Gastric ulcers
Chronic use - AKI, interstitial nephritis, UGI bleeds
Reye’s syndrome in post-viral children
Overdose –> Resp. alkalosis –> eventual metabolic acidosis
What are the ADP receptor inhibitors?
What are their toxicities?
Clopidogrel, Ticlopidine, Pasugrel, Ticagrelor
Irreversibly bind ADP receptors –> PLT’s don’t activate or display GPIIb/IIIa –> cannot aggregate
Ticlopidine –> neutropenia (Presents w/ fever & stomatitis)
What are the Xa inhibitors?
IIa inhibitors?
Xa inhibitors have X in the name:
Apixaban
Rivaroxaban
Idraparinux
IIa inhibitors have a G in the name:
Argatroban
Dabigatran
What are the phosphodiesterase III inhibitors?
What is their mechanism?
PDEIII inhibitors = Cilostazol, Dipyridamole
PDE III inhibition –> ^cAMP –> PLT aggregation inhibited & vasodilation
Used for intermittent claudication, angina prophylaxis
What are the GPIIb/IIIa inhibitors?
GPIIb/IIIa inhibitors = Abciximab, Eptifbatide, Tirofiban
Used for angioplasty & ACS
What is the mechanism of Cytarabine?
Pyrimidine analog –> inhibitor of DNAP
Can cause pancytopenia
What is the mechanism of Dactinomycin?
What is its toxicity?
Dactinomycin intercalates into DNA
Used for childhood tumors! (Wilms’, Ewing’s sarcoma, rhabdomyosarcoma)
Can cause myelosuppression
What is the mechanism of Doxorubicin?
What are its toxicities?
Doxorubin/Daunomycin intercalate into the DNA & inhibit TopoII
Toxicities:
Cardiotoxic (prevented with Dexrazoxane)
Vesicant
Myelosuppression
What is the mechanism of Bleomycin?
What are its toxicities?
Bleomycin induces free-radical formation –> dsDNA breaks
Toxicities:
Pulmonary fibrosis
Skin hyperpigmentation
What is the mechanism of Cyclophosphamide?
What are its toxicities?
Cyclophosphamide/Ifosphamide are alkylating agents
–> Crosslink DNA at guanine N-7 position
Toxicities:
Hemorrhagic cystitis (Mesna prevents)
Myelosuppression
Sterility
What are the nitrosureas?
What is their use?
Carmustine, Lomustine, Semustine, Streptozocin
They are alkylating agents that can cross the BBB –> used for brain tumors. They can cause CNS toxicities (ataxia, dizziness)
What is the mechanism of Busulfan?
What are its toxicities?
Busulfan is an alkylating agent used for CML & ablation of bone marrow prior to BMT
Toxicities:
Pulmonary fibrosis
Skin hyperpigmentation
What is the mechanism of Vincristine?
What are its toxicities?
Vincristine & Vinblastine block polymerization of microtubules –> inhibit mitotic spindle formation.
Toxicities:
Vincristine - peripheral neuropathy
Vinblastine - bone marrow suppression (blasts bone marrow)
What is the mechanism of Cisplatin?
What are its toxicities?
Cisplatin, Carboplatin, & Oxaliplatin –> crosslink DNA
Cisplatin - Nephrotoxic & ototoxic
Carboplatin - Myelosuppression
Oxaliplatin - Paresthesias & cold sensitivity
What is the mechanism of Hydroxyurea?
What are its toxicities?
Hydroxyurea inhibits ribonucleotide reductase (UDP –> dUDP)
Toxicities:
Bone marrow suppression
What is the mechanism of Imatinib?
What are its toxicities?
Imatinib is a bcr-able tyrosine kinase inhibitor
Used in CML & GIST
Toxicity:
Fluid retention
What is the mechanism of Rituximab?
What is it used for?
mAb against CD20
Used in Non-hodgkin’s lymphoma, RA
What is the mechanism of Vemurafenib?
What is its use?
Small molecule inhibitor of B-raf kinase with V600E mutation
Used to treat metastatic melanoma
What is the mechanism of Bevacizumab?
mAb against VEGF –> inhibits angiogenesis
What bugscause bacteremia in a sickle cell patient?
Strep pneumo > H. flu
They are functionally asplenic –> encapsulated organisms
Also don’t forget that they get Salmonella osteomyelitis
What types of collagen are defective/deficient in inherited diseases?
Type I –> Osteogenesis imperfecta
Type II
Type III –> Ehlers-Danlos Syndrome
Type IV –> Alport Syndrome
How many calories are present in 1 gram of: Protein Fat Carbohydrate Ethanol
Protein & Carbs = 4 cal
Fat = 9 cal
Ethanol = 7 cal
What is Clozapine used for?
What toxicities are seen with it?
It is an atypical antipsychotic used when other antipsychotics have all failed (it’s the big gun).
Toxicities:
Agranulocytosis!
Significant weight gain
Seizures
When are ACE inhibitors contraindicated?
Bilateral renal artery stenosis (these pts are dependent on ACE-mediated constriction of efferent arteriole to maintain GFR) –> ARF if administered
Also Pregnancy (teratogen)
What are the layers of the epidermis?
“Cancel Lab, Get Some Beer”
Corneum Lucidum (only present on thick skin) Granulosum Spinosum Basale
Where are apocrine glands found?
Armpits, genitals, and nipples
Secrete milky viscous fluid. Stinks because of bacteria.
What are the epithelial cell junction types & their compositions?
Tight junctions = Claudins & Occludens
Adherens junctions = Cadherins (link to actin)
Desmosomes = Desmogleins (link to keratin)
Gap junctions = Connexins form Connexons
Hemidesmosomes (bind basement membrane)
Integrins (bind laminin in BM)
What landmark is used for a pudendal nerve block?
A lumbar puncture?
Pudendal n. block (childbirth) –> Ischial spine
Lumbar puncture –> Iliac crest
What are the rotator cuff muscles & their functions?
SITS:
Supraspinatus –> initial abduction (most common RC injury)
Infraspinatus –> laterally rotates arm (pitching injury)
Teres minor –> adducts & laterally rotates
Subscapularis –> adducts & medially rotates
What nerve is affected by this injury?
Humerus surgical neck fracture or dislocation
Axillary nerve –> deltoid atrophy & numbness over deltoid
What nerve is affected by this injury?
Subluxation of radius
Radial nerve (deep branch) –> wrist drop & numb dorsal hand/snuffbox
What nerve is affected by this injury?
Midshaft humerus fracture
Radial nerve –> wrist drop & numb posterior hand/snuffbox
What nerve is affected by this injury?
Supracondylar humerus fracture
Proximal Median nerve –> Pope’s blessing & lateral hand numbness
What nerves contribute to the branches of the brachial plexus?
C5, C6, C7, C8, T1
“The 3 Musketeers Assasinated 5 Rats, 5 Mice, & 2 Unicorns”
Musculocutaneous - C5,6,7 Axillary - C5,6 Radial - C5,6,7,8,T1 Median - C5,6,7,8,T1 Ulnar - C8,T1
What nerve is affected by this injury?
Lunate dislocation
Distal median nerve –> median claw (can’t extend 2 & 3)
What can cause distal ulnar injury?
What is seen?
Fractured hook of the hamate –> distal ulnar claw (cannot extent 4th & 5th digits)
What causes Erb-Duchenne palsy?
Waiter’s tip - caused by torn upper trunk of brachial plexus (C5,6) seen in infants following delivery
What causes a Klumpke claw?
Torn lower trunk of brachial plexus (C8, T1). This can occur by pulling a baby out by its arms, falling and catching oneself on a tree branch, or thoracic outlet syndrome.
What causes thoracic outlet syndrome?
What is seen?
Compression of the brachial plexus & subclavian vessels between the anterior & middle scalene (superior thoracic outlet).
Symptoms: Atrophy of intrinsic hand muscles Pain/paresthesias Decreased pulses in the arm Edema
What carpal injuries can occur by falling on an outstretched hand?
What are the complications?
Fractured scaphoid –> avascular necrosis
Dislocated lunate –> acute carpal tunnel syndrome (median n.)
Fractured hook of hamate –> ulnar n. injury
When does clawing of the hand occur?
Clawing occurs with more distal lesions, because the deficit is pronounced even at rest. More proximal lesions present with deficits only when the muscle is used.
What common drugs have antimuscarinic effects?
Atropine TCA's H1 blockers (diphenhydramine, etc.) Neuroleptics Antiparkinsonian drugs
What are the contraindications of metformin?
Renal failure Liver failure CHF Alcoholism Sepsis
Anything that could predispose to lactic acidosis
What is cataplexy?
Sudden loss of motor tone triggered by emotion. This is seen in narcolepsy.
What substance is deficient in the CSF in narcolepsy?
Hypocretin-1 & Hypocretin-2
(Orexin-A & Orexin-B)
Produced in the lateral hypothalamus, they promote wakefulness.
What side effects are seen with low potency first generation antipsychotics?
High potency?
Low potency –> blockade of:
Cholinergic receptors –> anticholinergic
Histamine receptors –> sedation
Noradrenergic receptors –> orthostatic hypotension
High potency:
Extrapyramidal symptoms
What receptors are antagonized by TCA’s?
Histamine –> sedation
Alpha adrenergic –> orthostatic hypotension
Cholinergic –> anticholinergic effects
What must be monitored in a pt on thiazolidinediones?
A pt on TZD’s (Rosiglitazone, etc.) must have their LFT’s monitored.
What adverse effects are seen with Foscarnet?
Foscarnet binds the pyrophosphate binding site on viral RNA polymerase. Second line for CMV retinitis & HSV.
Adverse effects:
Nephrotoxicity
Hypocalcemia
Hypomagnesemia
What are the long, intermediate, & short acting insulins?
Short:
Lispro, Aspart, Glulisine
Intermediate:
NPH > Regular insulin
Long:
Glargine
Detemir
What is the equation for physiologic dead space?
Physiologic DS = anatomic DS + V/Q mismatch
DS = TV*(PaCO2-PeCO2)/PaCO2
What risks are associated with Common Variable Immunodeficiency?
Increased risk of autoimmune disease & lymphoma
What is the outcome of vertical transmission of HBV?
Immature infant immune system:
Mild initial illness
High chance of chronic infection
What is the treatment for toxoplasmosis?
Sulfadiazine & Pyrimethamine
What are the most common causes of focal brain lesions in HIV patients?
Toxoplasma
Primary CNS lymphoma
What is used to treat hypertension in pregnant women?
Methyldopa
What is the adenoma-to-carcinoma progression of CRC?
Normal colon –> APC mutation –> Proliferation –> K-RAS mutation –> Adenoma –> p53 mutation –> Carcinoma
Order is AK-53
What is considered fever?
What is dangerous to brain tissue?
What causes death?
Fever > 101.0 (38.3)
Neurological sequelae = 42 degrees
Death = 43 degrees
What is hyperpyrexia?
What is the treatment for hyperpyrexia?
Hyperpyrexia is a temperature > 40 degrees
Treatment is NSAIDs/Acetaminophen & physical cooling of the body.
What are the risk factors for cervical cancer?
Multiple sexual partners
Cigarette smoking
Early coitarche
Low socioeconomic status
What drugs improve mortality in CHF patients?
ACE inhibitors
Beta blockers (unless decompensated)
ARB’s
Spironolactone
What is seen with left-sided CHF?
Pulmonary edema
Paroxysmal nocturnal dyspnea
Orthopnea
Hemosiderin-laden macrophages
What is seen with right-sided CHF?
Chronic passive congestion –> hepatosplenomegaly
(nutmeg liver)
Peripheral dependent pitting edema
JVD
What causes acute bacterial endocarditis?
Subacute?
Acute = S. aureus –> large vegetations on a normal valve
Subacute = Viridans strep –> small vegetations on congenitally abnormal or diseased valves
What can cause culture-negative endocarditis?
Malignancy Hypercoagulability Lupus (Marantic/Libman-Sacks) HACEK organisms: -Hemophilus -Actinobacillus -Cardiobacterium -Eikenella -Kingella
What are the signs/symptoms of bacterial endocarditis?
bacteria FROM JANE
Fever Roth's spots (IC mediated) Osler's nodes (Painful; IC mediated) Murmur Janeway lesions (Painless; septic emboli) Anemia (of chronic disease) Nail bed hemorrhage Emboli
What complications can result from bacterial endocarditis?
Chordae rupture
Glomerulonephritis
Suppurative pericarditis
Emboli
How is diagnosis of rheumatic fever made?
JONES criteria
Joints (migratory polyarthritis)
s chorea
Minor criteria: Fever, ^ESR
What is seen early in chronic rheumatic heart disease?
Late?
Early death = myocarditis
Rheumatic heart disease affects Mitral > Aortic»_space; Tricuspid
Early lesion - mitral regurgitation
Late lesion - mitral stenosis
What is seen histologically with rheumatic heart disease?
Aschoff bodies (granulomas) Anitschkow's cells (activated histiocytes)
Caused by a Type II hypersensitivity reaction from Ab’s against M protein.
What is seen with acute pericarditis?
Sharp pain (worse w/ inspiration, better w/ leaning forward)
Friction rub
ST elevation in all leads
What are the types of pericarditis & their causes?
Fibrinous - Dressler’s syndrome, uremia, radiation
Serous - viral pericarditis, inflammatory diseases (SLE, RA, etc.)
Suppurative - bacterial pericarditis (rare due to abx)
What is seen with cardiac tamponade?
Beck's triad: -Hypotension -JVD -Distant heart sounds Pulsus paradoxus Electrical alternans
Pulsus paradoxus - systolic BP decreases by at least 10 mmHg upon inspiration
What can cause pulsus paradoxus?
Pulsus paradoxus - systolic BP decreases by at least 10 mmHg upon inspiration
Caused by: Cardiac tamponade Pericarditis Asthma Obstructive sleep apnea Croup
What cardiac tumors are seen?
Myxoma - Adults; ball-valve obstruction in the LA (syncope)
Rhabdomyoma - Kids; associated with tuberous sclerosis
Metastasis - Often to pericardium (effusion). Melanoma, lymphoma
What is Kussmaul’s sign?
What is it seen in?
^ in JVP upon inspiration rather than a decrease
Seen in: Constrictive pericarditis Restrictive cardiomyopathy RA or RV tumors Cardiac tamponade
Who is classically affected by Takayasu’s arteritis?
Asian females under 40
What is seen in Takayasu’s arteritis?
“Pulseless disease” (weak UE pulses)
Visual & neurologic symptoms
^ESR
Basically the same disease as Giant Cell arteritis but occurs at the aortic arch & proximal great vessels.
What is seen with Polyarteritis Nodosa?
HBV seropositivity Fever, weight loss, Abdominal pain w/ melena Hypertension Renal damage Neurologic symptoms (wrist/foot drop) "String of pearls" on arteriogram Fatal if untreated
SPARES THE LUNGS
Who is classically affected by polyarteritis nodosa?
What is seen histologically?
Young adults
Transmural inflammation with fibrinoid necrosis
What is seen in Kawasaki disease?
Fever Cervial LAD Conjunctivitis Strawberry tongue (mucocutaneous LN syndrome) Desquamating rash on palms & soles
Can lead to coronary MI or aneurysm/rupture
What is the treatment for Kawasaki disease?
IVIg & high-dose aspirin
What autoAb’s are seen in Kawasaki disease?
Anti-endothelial or anti-smooth muscle Ab’s
What is seen with microscopic polyangiitis?
Hemoptysis
RPGN
Palpable purpura
p-ANCA’s
NO granulomas, NO eosinophilia
What is seen with Granulomatosis & Polyangiitis?
Wegener’s
Granulomas Sinusitis/Nasopharyngeal ulceration Hemoptysis (CXR shows large nodular densities) RPGN c-ANCA's
What is seen with Churg-Strauss syndrome?
Asthma, sinusitis Palpable purpura Peripheral neuropathy Granulomas with eosinophilia RPGN p-ANCA ^IgE
What is seen with Henoch-Shonlein purpura?
Most common systemic childhoos vasculitis Follows an URI Palpable purpura on buttocks/legs Arthralgia Abdominal pain w/ melena IgA nephropathy
What are c-ANCA’s & p-ANCA’s against?
c-ANCA = PR3-ANCA
p-ANCA = MPO-ANCA
What is seen with a strawberry hemangioma?
Benign capillary hemangioma of infancy.
Grows rapidly and regresses spontaneously by 5-8y
What is seen with a cherry hemangioma?
Benign capillary hemangioma of the elderly
Does not regress
What is a pyogenic granuloma?
Polypoid capillary hemangioma that can ulcerate & bleed.
Associated with trauma & pregnancy
What is a cystic hygroma?
Cavernous lymphangioma of the neck
Associated with Turner syndrome
What is a Glomus tumor?
Benign, painful red/blue tumor under the fingernail
Arises from glomus body
What is a bacillary angiomatosis?
Benign capillary lesion found in AIDS patients
Caused by Bartonella henselae infection
Looks like Kaposi’s sarcoma
Where are angiosarcomas typically found?
Head, neck, & breast following radiation
Liver due to PVC, arsenic, & Thorotrast exposure
What causes Kaposi’s sarcoma?
Endothelial malignancy of skin, mouth, GI, & respiratory tract
Caused by HHV-8 & HIV together
Seen in old Eastern European males, HIV pts, & transplant pts
What is seen with Sturge-Weber disease?
Port wine stain on face (trigeminal distribution)
Ipsilateral (to port wine stain) leptomeningeal angioma
Seizures
Early-onset glaucoma
It is a vascular disorder that affects the small vessels.
What mutation causes Von Hippel-Lindau disease?
What neoplasms are seen in Von Hippel-Lindau disease?
Autosomal dominant deletion of VHL gene on chromosome 3p
Cerebellar hemangioblastomas
Clear cell renal carcinoma
Pheochromocytomas
What causes “housemaid’s knee?”
Prepatellar bursitis. Seen in patients who do a lot of kneeling.
How many organisms are required to establish cholera?
Usually 10^10
Anything that decreases gastric acid can cause susceptibility (PPI’s, food ingestion, achlorhydria)
What is the most common cause of aortic stenosis?
Senile calcific aortic stenosis
Presents in 70’s or earlier if bicuspid aortic valve is present.
What are the triggers for Gilbert hyperbilirubinemia?
Fasting Stress Hemolysis Physical exertion Febrile illness Fatigue
From where do the bronchial arteries arise?
Where do they empty?
Arise from the descending thoracic aorta.
Most of the venous blood is returned via the pulmonary veins. This accounts for part of the A-a gradient.
What type of glucose are the GLUT transporters selective for?
They are somewhat selective for D-glucose
What are the insertion points of the SCM?
Sterno –> Sternum
Cleido –> Clavicle (medial portion)
Mastoid –> Mastoid process
What drug is used to prevent cisplatin nephrotoxicity?
What is its mechanism?
Amifostine scavenges free radicals. Chloride diuresis (IV NaCl) is also used to keep cisplatin in a nonreactive state while in the kidney.
What drug is given to prevent Doxorubicin/Daunomycin cardiotoxicity?
Dexrazoxane (iron chelating agent)
What is the “female athlete triad”?
Eating disorder
Amenorrhea
Osteoporosis
What is caused by rat poison?
What is the antidote?
Rat poison is like a long-acting warfarin.
Thus, the treatment to prevent bleeding is fresh frozen plasma.
What drug is used to treat bradycardia secondary to RCA infarction?
What is a possible acute side effect?
Atropine can be used to block vagal outflow to the SA & AV nodes.
This can cause acute closed-angle glaucoma in susceptible patients. It is absolutely contraindicated in a patient with preexisting glaucoma.
How is congenital adrenal hyperplasia treated?
Low dose corticosteroids —> inhibition of ACTH –> suppression of HPA axis
Where do Cushing ulcers arise?
Curling ulcers?
Cushing ulcers can be in the esophagus, stomach, or duodenum. They arise due to ^ICP.
Curling ulcers are found in the proximal duodenum only.
They arise due to severe trauma/burns –> decreased oxygenation
What can cause gallbladder hypomotility?
Pregnancy
Rapid weight loss
Long-term TPN or octreotide
High spinal cord injuries
Why is spironolactone beneficial in CHF patients?
It is likely due to inhibition of ventricular remodeling & cardiac fibrosis (normally facilitated by aldosterone).
What are the effects of nitroprusside?
It is a balanced arterial & venodilator. This causes decreased preload and afterload.
What are the eukaryotic promoters?
CAAT (-75) & TATA (-25)
What are the advantages of COX 2 inhibitors?
Less risk of bleeding
Less GI ulceration
They have a higher risk of clotting though.
What nerve injury is seen with subluxation of the radial head?
Damage to the deep branch of the radial nerve –> wrist drop without sensory deficit
What is the function of P-glycoprotein?
It is an ATP-driven efflux pump that is often upregulated in tumor cells & can cause resistance to chemotherapy.
What is the mechanism of shiga toxin?
Alter the 60S ribosomal subunit to prevent tRNA binding to the ribosome –> inhibit translation
What is the most common risk factor for native valve endocarditis in the US?
Mitral valve prolapse
What are the sizes of petechiae, purpura, & ecchymoses?
Petechiae < 5mm
5 mm < Purpura < 1 cm
Ecchymoses >1cm
What is the mechanism of diabetic neuropathy?
1) Aldose reductase conversion of intracellular glucose to sorbitol –> osmotic damage to axons & schwann cells
2) Hyaline arteriolosclerosis of endoneural arterioles –> ischemic nerve damage
What bugs typically cause reactive arthritis?
Reider's syndrome is typically caused by: Chlamydia Campylobacter Salmonella Shigella Yersinia
What signaling molecules work through increases in cGMP?
Atrial natriuretic peptide
Nitric oxide
What hormones exert their effects through an increase in cAMP?
Glucagon
TSH
PTH
What is seen in Diffuse Esophageal Spasm?
Painful, disorganized, sustained esophageal contractions
“Corkscrew esophagus” on barium swallow
Intermittent dysphagia & chest pain
What is used as a serum marker of anaphylaxis?
Tryptase
It is released (with histamine) from mast cells & is relatively specific to them.
What is the intrapleural pressure at rest?
Intrapleural pressure at FRC = -5 cm H20
What does Parvovirus interact with on host cells?
P antigen on immature erythroid cells
Can also infect mature ones but has tropism for immature
What is the major determinant of E. coli virulence in neonatal meningitis?
K-1 capsular antigen
What receptor is responsible for nicotine addiction?
alpha-4-beta-2 nicotinic ACh receptor –> downstream dopamine release
What is the mechanism of Verenicline?
It is an alpha-4-beta-2 nicotinic receptor partial agonist used to reduce nicotine cravings & attenuating the reward pathway of nicotine
What medications cause fat redistribution from the extremities to the abdomen?
Protease inhibitors (lipodystrophy) Corticosteroids (Cushing's)
What vessels can cause compression of CNIII?
Posterior cerebral artery
Superior cerebellar artery
CNIII runs between these vessels & aneurysm in either one can cause compression of it.
With CNIII palsy, what type of injury causes GVE symptoms?
GSE symptoms?
Compression tends to cause GVE symptoms –> pupillary reflexes
Ischemia tends to cause GSE symptoms –> motor palsy
What can cause autoimmune degeneration of the cerebellum?
Paraneoplastic syndromes from:
Breast/ovary (anti-Yo)
Lung (Anti-P/Q; Anti-Hu)
Which pneumoconiosis is associated with eggshell calcification of hilar LN’s?
Silicosis
What causes bronchiolitis obliterans?
What is seen?
Chronic rejection of a transplanted lung –> lymphocytic inflammation & necrosis of bronchiolar walls –> granulation tissue & exudate in the lumen of the bronchioli –> fibrous tissue obliteration of small airways
What can cause clubbing of the fingers?
Lung diseases - cancer, TB, CF, bronchiectasis, pulmonary HTN, any with hypoxia. This is the most common cause.
Heart diseases - cyanotic (5 T’s), bacterial endocarditis
Other - IBD, hyperthyroidism, malabsorption
What is the germ tube test?
Inoculate Candida albicans into serum at 37 degress for 3h –> true hyphae will sprout from the yeast (often look like little J’s)
What is the histology of a lung hamartoma?
Hyaline cartilage
Fat, smooth muscle, clefts
Lined by respiratory epithelium
Generally present as a peripheral “coin lesion”
What is derived from the foregut?
Everything coming off of the celiac trunk: Esophagus Stomach Liver Gallbladder Pancreas Upper duodenum
What is derived from the midgut?
Everything supplied by the SMA: Lower duodenum Small intestine Ascending colon Proximal 2/3 of the transverse colon
What is derived from the hindgut?
Everything supplied by the IMA:
Distal 1/3 of the transverse colon
Descending colon
Sigmoid colon
What can be seen with intestinal malrotation?
Intestinal obstruction –> bilious vomiting in first week of life
Cecum in RUQ, fixed by Ladd’s fibrous bands
Midgut volvulus –> gangrene or perforation
What is the equation for attributable risk percentage?
ARP = (RR-1)/RR
What is Cheyne-Stokes breathing?
What is it seen in?
Repeating episodes of breathing followed by an apneic period
Seen in advanced heart disease & neurologic disease. It is caused by a delayed response to increases in PaCO2.
What is seen clinically with cerebral amyloid angiopathy?
Recurrent small hemorrhagic strokes in multiple brain locations, especially outside of the basal ganglia & in the hemispheres.
What is the treatment for insomnia associated with jet lag?
Melatonin
What are the portacaval anastomoses?
They link the portal vein to the systemic venous circulation
1) Left gastric vein –> Esophageal vein
(Esophageal varices)
2) Superior rectal vein –> Middle & inferior rectal veins
(Hemorrhoids)
3) Paraumbilical veins –> Superficial & inferior epigastric veins
(Caput medusae)
What species cause mucormycosis?
Mucor
Rhizopus
Absidia
What bacterium requires media with cholesterol?
Ureaplasma urealyticum requires special media rich in urea & cholesterol to grow. It can cause urethritis.
What can be caused by use of appetite suppressants?
Fenfluramine
Phentermine
(Fen-Phen)
If ingested for >3 months, they can cause pulmonary hypertension. Classic presentation is dyspnea on exertion –> cor pulmonale (RVH) –> sudden cardiac death.
When are MAOI’s desirable?
Atypical depression
What are the fever cycle lengths of the various species of Plasmodium?
vivax/ovale - 48h
malariae - 72h
falciparum - severe & disorganized
What is the PMN count in a gouty joint?
Normally < 20,000
If the PMN count is much greater than this, indicates a septic arthritis.
What molecule (contained in food) should be avoided in patients taking MAOI's? What is seen if it is ingested?
Tyramine should be avoided. It is a sympathomimetic usually degraded in the GI tract.
If ingested, it can cause hypertensive crisis.
This is the most commonly tested side effect on boards.
What are the long acting benzodiazepines?
Diazepam
Flurazepam
Chlordiazepoxide
Clorazepate
What are the short-acting benzodiazepines?
Alprazolam
Triazolam
Oxazepam
What should be considered if jejunal ulcers are present?
Gastrinoma
Jejunal ulcers are almost never caused by your everyday PUD. Also consider if the gastrinoma is part of MEN1
What are the possible sequelae of GAS impetigo?
Strep throat?
Impetigo –> only Acute post-strep GN only
Strep throat –> Acute post strep GN or Rhematic fever
Rheumatic fever can only follow strep pharyngitis.
What breathing rates are adopted by patients with COPD?
Restrictive –> higher breathing rates of low tidal volume
Obstructive –> lower breathing rates of high tidal volume
This minimizes the work of breathing for them.
Why are gallstones formed during pregnancy?
Estrogen –> ^HMG-CoA reductase activity –> ^Cholesterol
Progesterone –> Gallbladder hypomotility & reduced bile acids
Also seen with OCP use.
What antiarrhythmic should be used in post-MI arrhythmia?
Lidocaine
Mexiletine
Tocainide
They are selective for depolarized cells (ischemic myocardium). Amiodarone is the DOC for V-tach.
What drug is the best treatment for AChE inhibitors?
Pralidoxime
It can only be used early on. Atropine is an alternative, though it will only combat the muscarinic effects. The patient will still be at risk for muscle paralysis.
What causes a Zenker’s diverticulum?
Cricopharyngeal muscle dysfunction –> increased oropharyngeal pressure during swallowing –> herniation through the muscular wall
What does a relative afferent pupillary defect indicate?
A positive swinging flashlight test indicates pathology involving the retina, optic nerve, optic chiasm, or optic tract. If the pathology was after this, the pupillary light reflex would be intact.
What side effects are seen with Niacin?
High dose niacin (to treat dyslipidemia) can cause: Flushing Gout Hyperglycemia Hepatitis
What step in the TCA cycle produces GTP?
Succinate thiokinase
Succinyl-CoA Synthetase
Where is cryptococcus found in the environment?
Soil & bird (pigeon) droppings
Who is at risk for being lactose intolerant?
Asian & African descent
Can also be secondary to viral gastroenteritis or any disease that damages the intestinal epithelium
What is the mechanism of Niacin’s effects on dyslipidemia?
Decreases the synthesis of hepatic TG’s & VLDL.
Also increases HDL (drug of choice)
How are patients screened if fat malabsorption is suspected?
Sudan III stain on a stool sample reveals presence of fat
What coagulopathy is seen with uremic patients?
^bleeding time, normal PLT count, PT & aPTT
It is a qualitative platelet defect due to under-excretion of platelet inhibitory factors. Resolves with dialysis.
Where is a hydrocele located?
Within the tunica vaginalis of the testicle
It is derived from the peritoneum and can remain in communication to the peritoneal cavity, leading to hydrocele.
What is the basis for chloride shift seen in RBC’s?
CO2 (tissues) –> H+ & HCO3- –> HCO3- diffuses out –> Cl- diffuses in to maintain charge
The reverse happens in the lungs. Thus, RBC [Cl-] is high in venous blood and low in arterial blood.
What drug is used in acute closed-angle glaucoma?
What drug is contraindicated?
Use Pilocarpine (cholinomimetic –> opens meshwork)
Do NOT use epinephrine (effective at vasoconstricting to reduce production of aqueous humor but causes mydriasis –> blocks off canal of Schlemm)
What is the mechanism of opioids?
Agonists at mu opioid receptors –> opens K+ channels & closes Ca2+ channels –> inhibition of synaptic transmission
Inhibits release of ACh, NE, 5-HT, glutamate, substance P
What toxicities are seen with opioids?
Addiction Respiratory depression Constipation Miosis Additive CNS depression with other drugs
OD treated with naloxone
What is Butorphanol?
What is it used for?
It is a mu opioid receptor partial agonist used for severe pain. It has less respiratory depression than other opioids.
If given to a pt who is dependent on a normal opioid, can cause withdrawal.
What is the mechanism of Tramadol?
What toxicities are seen?
It is a weak opioid agonist that also inhibits NE & 5-HT reuptake. It is used for chronic pain.
It has toxicities similar to opioids & can lower the seizure threshold.
What is the drug of choice for partial seizures?
Carbamazepine
Both simple & complex partial seizures.
What is used to prevent status epilepticus?
Phenytoin
What toxicities are seen with Carbemazepine?
Agranulocytosis Aplastic anemia SIADH Ataxia CYP450 induction Teratogenesis
What toxicities are seen with Phenytoin?
Nystagmus Drug-induced Lupus Gingival hyperplasia Hirsutism Megaloblastic anemia LAD Ataxia CYP450 induction Teratogenic (fetal hydantoin syndrome)
What toxicities are seen with valproic acid?
Tremor
Weight gain
Fatal hepatotoxicity (measure LFT’s)
Neural tube defects (don’t give in pregnancy)
What is the mechanism of barbiturates?
^DURATION of Cl- channel (GABAa) opening –> hyperpolarizes membrane –> decreases neuronal firing
What is the mechanism of benzodiazepines?
Increase FREQENCY of GABAa channel opening –> influx of Cl- –> hyperpolarization of neurons
What toxicities are seen with bezodiazepines?
What is the treatment for overdose?
CNS depression (seen in elderly; additive) Dependence (Triazolam, Oxazepam, Midazolam)
OD Tx: Flumazenil (antagonist)
What are the common CNS depressants?
EtOH Benzodiazepines Barbiturates 1st generation antihistamines Neuroleptics
What is the mechanism of Zolpidem?
Zolpidem, Zaleplon, & Eszopiclone
They are selective GABA agonists at the BZ1 receptor subtype. Used for insomnia.
What determines potency of an inhaled anesthetic?
^lipid solubulity
Potency = 1/MAC
What factors influence MAC?
Minimum alveolar concentration to anesthetize 50% of population
Affected ONLY by:
Age
Body temperature
What toxicity is seen with Halothane?
Hepatotoxicity:
A few days after exposure: Eosinophilia, ^ALT, ^PT
What toxicity is common to all inhaled anesthetics?
Malignant hyperthermia
not seen in N2O actually
What inhaled anesthetic is pro-convulsant?
Enflurane
What are the IV anesthetics?
Barbiturates Benzos Arylcyclohexamines (Ketamine) Opioids Propofol
What barbiturate is used for anesthetic induction?
Thiopental
It is highly lipid soluble (rapid onset) & redistributes rapidly (effects are short-lived)
What is propofol used for?
What is its mechanism?
Sedation for mechanically ventilated patients
Anesthesia induction
Short procedures
Potentiates GABAa
What are the ester local anesthetics?
The amides?
Ester = Procaine, Cocaine, Tetracaine
Amide = Lidocaine, Mepivacaine, Bupivacaine
Amide’s have 2 I’s in the name
What can be coadministered to increase effectiveness of local anesthetics?
Epinephrine can be given to vasoconstrict –> ^local action & decrease systemic concentration
What fibers are affected more by local anesthetics?
What sensations are lost first due to this?
Small myelinated > Small unmyelinated > Large myelinated > Large unmyelinated
Loss of sensation:
1) Pain
2) Temperature
3) Touch
4) Pressure
What is the mechanism of Dantrolene?
What is its use?
Blocks release of Ca2+ from the SR of skeletal muscle
Used to treat:
Malignant hyperthermia (inhaled anesthetics except N2O)
Neuroleptic malignant syndrome
What drugs are used to treat Parkinson’s disease?
BALSA: Bromocriptine Amantadine Levodopa Selegiline (and COMT inhibitors) Antimuscarinics
What is the mechanism of Bromocriptine?
What is it used for?
It is a D2 agonist used for Parkinson’s disease & Prolactinomas
What toxicities are seen with Levodopa/Carbidopa?
Anxiety, agitation, insomnia, confusion, hallucinations
Arrhythmias
Dyskinesia
What is the mechanism of Selegiline?
Selective MAO-B inhibitor –> inhibits metabolism of Dopamine
What drugs are used to treat Alzheimer’s?
Memantine (NMDA antagonist)
Donepezil, Ganatamine, Rivastigmine (AChE inhibitors)
alpha-Tocopherol (Vit. E; Antioxidant)
What drugs are used to treat Huntington’s disease?
Tetrabenazine, Reserpine (inhibit VMAT -> dop not packaged)
Haloperidol (Dopamine antagonist)
What toxicities are seen with Sumatriptan?
Coronary vasospasm (contraindicated in Prinzmetal’s angina)
What is significant about Selective IgA Deficiency?
1) They have anaphylactic reactions to IgA-containing blood products
2) Can have false-positive hCG testing (heterophile Ab)
Mutation in X-linked agammaglobulinemia
BTK (Bruton’s Tyrosine Kinase)
No B cell maturation seen –> less B cells & way less Ig’s of all classes
What is seen histologically with Dubin-Johnson syndrome?
Epinephrine metabolites are seen within the lysosomes
Grossly, liver is black
What immune cell predominance is seen in bronchoalveolar lavage of a sarcodosis patient?
Very high CD4:CD8 ratio
What prokaryotic rRNA binds the Shine-Dalgarno sequence?
16S rRNA is complementary to the Shine-Dalgarno sequence (10 bp upstream from AUG)
What is the mechanism of Aminoglycosides?
Bind 30S and inhibit formation of initiation complex
What is the mechanism of Tetracyclines?
Bind 30S and prevent tRNA from entering acceptor site
What is the mechanism of Chloramphenicol?
Binds 50S and inhibits peptidyl transferase
What is the mechanism of Macrolides?
Bind 50S and prevent release of tRNA from the E site
What illness is caused by B. pertussis?
Whooping cough
3 stages:
1) Catarrhal stage - flu-like; highly contagious
2) Paroxysmal stage - many coughs then large whooping inspiration
3) Recovery stage - coughing slowly subsides
Whole process lasts ~3 months
What is the mechanism of diphtheria toxin?
AB exotoxin ribosylates EF-2 –> inhibits protein synthesis leading to cell death
What step is NAD+ needed for in glycolysis that is the basis for why it is regenerated in anaerobic glycolysis?
Glyceraldehyde-3-P –> 1-3-BPG
What organism causes tinea versicolor?
aka pityriasis versicolor
Caused by Malassezia furfur
Symptoms:
Light patches on skin
Otherwise asymptomatic
What is seen on KOH prep of Malassezia furfur?
Spaghetti & meatballs appearance
Causes tinea versicolor
What nutrients are not present in breast milk?
Vitamins D & K
D levels will be adequate if the infant gets enough sunlight. Dark skinned children are at higher risk.
K is administered at birth
What are the possible complications of Diphtheria?
Suffocation due to pseudomembranes
Heart pathology - myocarditis, arrhythmia, CHF
CNS pathology - neuropathy, paralysis, coma
What is the Diphtheria vaccine against?
The B portion of the AB exotoxin
A = active (ribosylates EF-2) B = binding
What resting membrane potential do nerves typically sit at?
-70 mV
What organisms cause nongonococcal urethritis?
Chlamydia trachomatis > Ureaplasma urealyticum»_space; Mycoplasma & Trichomonas
Azithromycin is the treatment
What is the drug of choice for the management of hypertensive pts who also have bradycardia?
Nifedipine
It is a vascular-selective CCB that causes vasodilation and can cause compensatory tachycardia.
What is the cause of hereditary pancreatitis?
Abnormal trypsin cannot be cleaved and thus inactivated by other trypsin. Patients suffer recurrent attacks of acute pancreatitis.
What electrolyte disturbances can be caused by loop diuretics?
Hypokalemia
Hypomagnesemia
Hypocalcemia
What is seen with fibromyalgia?
Diffuse musculoskeletal pain
Insomnia
Emotional disturbances
Often seen in women 20-50
What are the 3 dopaminergic pathways within the brain?
Mesolimbic-Mesocortical –> regulates behavior
Nigrostriatal –> coordination of movement
Tuberoinfundibular –> controls prolactin secretion
What can persistent lymphedema lead to?
Lymphangiosarcoma
Often seen after radical mastectomy
What are the effects of AV shunts on the pressure-volume curve?
Increased preload and decreased afterload
What effects do loop diuretics have on the renal arterioles?
In addition to their effects at the thick ascending limb, loop diuretics stimulate prostaglandin release, causing vasodilation of the afferent arteriole.
This can be blocked by concurrent use of NSAIDs
What antiarrhythmics demonstrate use-dependence?
Use-dependence = prolong the QRS more at high HR’s
Class Ic (Na+ channel blockers) --> use-dependence Class III (K+ channel blockers --> reverse use-dependence
What are the opioid partial agonists?
Pentazocine & Butorphanol
They can cause withdrawal if full agonist opioids have been used.
What beta blockers are safer to use in diabetics?
B1 selective
The nonselective ones blunt the adrenergic symptoms normally seen with hypoglycemia. They also inhibit hepatic gluconeogenesis and peripheral glycogenolysis & lipolysis.
What molecule are bisphosphonates analogs of?
Pyrophosphate (a component of hydroxyapatite)
What is the cause of supine hypotension syndrome?
aka aortocaval compression syndrome
Caused by the gravid (>20 weeks) uterus compressing the IVC upon lying down. This reduces venous return, which lowers CO –> hypotension & possible syncope
How can the cause of a metabolic alkalosis be determined?
What are the causes?
Measurement of urinary [Cl-] & volume status
Vomiting –> low urinary Cl- (saline responsive)
Loop diuretics –> high urinary Cl- (saline responsive)
Conn syndrome –> high urinary Cl- (saline unresponsive)
What is defective in Hepatitis D virus?
It must be coated by the external coat antigen of HBV in order to survive & infect.
What drugs are typically coadministered with direct arterial vasodilators?
Sympatholytics (to counteract compensatory tachycardia)
Diuretics (to counteract sympathetic renin release –> edema)
What antiarrhythmics cause prolongation of the QT interval?
Class Ia & Class III
Amiodarone is the only drug of these classes that does not predispose to torsades.
What nerve is at risk when food is caught in the piriform recess?
Internal branch of the superior laryngeal nerve
Damage to it leave the patient with no sensation to the pharynx above the vocal cords –> no cough reflex
What is Terbinafine used for?
What is its mechanism?
What toxicities are seen?
Terbinafine is used for dermatophyte infections. It inhibits fungal squalene epoxidase –> impaired synthesis of ergosterol.
Toxicities:
Abnormal LFT’s
Visual disturbances
Not seen if used topically
What is the drug of choice in treating hairy cell leukemia?
Cladribine
It is an adenosine analog that is resistant to Adenosine Deaminase (usually a problem with treating HCL).
What toxicities are seen with carbamazepine?
Bone marrow suppression
Hepatotoxicity
SIADH
What drug is used to treat carcinoid syndrome?
Octreotide
It is a synthetic somatostatin analog
What is the treatment for cryptococcal meningitis?
Amphotericin B & flucytosine
What is the main toxicity of antithyroid drugs?
PTU & Methimazole both cause agranulocytosis
Typically presents with fever & a sore throat
Where are the leads placed for biventricular pacemakers?
Right atrium
Right ventricle
Left AV groove, within a vein of the coronary sinus
When do the neural pores close?
Anterior - 25th day
Posterior - 27th day
Failure in either of these leads to neural tube defects.
What is epidermal spongiosis?
Accumulation of edema in the epidermis –> intercellular bridges are stretched.
If the bridges tear –> vesicle
What can cause communicating hydrocephalus?
Meningitis
Subarachnoid hemorrhage
Intraventricular hemorrhage
What PO2 corresponds to 50% saturation of Hb?
Myoglobin?
Hemoglobin - 26 mmHg
Myoglobin - 1 mmHg
Therefore myoglobin has much higher affinity for O2 than does hemoglobin. It also has no cooperativity, leading to a steep, non-sigmoidal dissociation curve. Monomeric Hb acts very similarly to Mb.
What are neurofibromas composed of?
Schwann cell tumors
They are rubbery and exhibit “buttonholing”
What is released from the ventricles in response to volume overload?
BNP and even ANP can be released from the ventricles in severe volume overload/hypertrophy.
What changes occur in the skin in response to chronic topical corticosteroid application?
Dermal atrophy
Can present as loss of collagen, drying, cracking, tightening of the skin, telangiectasias & ecchymoses.
What is seen on water deprivation testing in primary polydipsia?
Primary (psychogenic) polydipsia
Strong increase in urine osmolarity due to water deprivation, then a weak increase following vasopressin injection.
What are penicillins structural analogs of?
D-Ala-D-Ala
What drugs can accumulate in slow-acetylators?
INH
Dapsone
Hydralazine
Procainamide
What is the mechanism of abciximab?
What is its use?
Anti-GPIIb/IIIa –> blocks platelet aggregation
Used during angioplasty
What are the effects of ANP?
1) Dilates afferent & constricts renal arterioles. Inhibits sodium reabsorption (PCT & CCD). Inhibits renin release.
2) Inhibits aldosterone secretion.
3) Peripheral vasodilation
What is the mechanism of Ethambutol?
Inhibits arabinosyltransferase –> impaired carbohydrate polymerization –> impaired cell wall synthesis
What can be coadministered to decrease the flushing seen with Niacin?
Aspirin
This is because the side effect is mediated by prostaglandins.
What is damaged in central diabetes insipidus?
Pituitary damage –> transient DI
Hypothalamus damage –> permanent DI
What is seen on liver biopsy of a patient with chronic HBV?
Ballooning degeneration
Hepatocyte necrosis
Portal inflammation
“Ground glass” appearance (intracellular HBsAg proteins)
What is seen on liver biopsy of a patient with chronic HCV?
Lymphoid aggregates in the portal tracts
Focal macrovesicular steatosis
What is the mechanism of ammonia intoxication in the brain?
Astrocytes take up NH4+ and combine it with glutamate to make glutamine –> accumulation & astrocyte damage. Also the glutamate content in the brain is then decreased.
Additionally, neurons can detoxify ammonia by combining it with alpha-Ketoglutarate –> glutamate. This depletes stores of alpha-Ketoglutarate –> impaired Krebs cycle within neurons.
What is the glutamate-glutamine cycle?
Neurons convert glutamine –> glutamate (Glutaminase) –> release it into synaptic cleft as a NT
Astrocytes take up glutamate and –> glutamine (Glutamine synthase) and release it for use by neurons.
How long is it before an infarcted myocyte ceases contracting?
How long until injury is irreversible?
Affected myocytes cease contracting within ~1 minute.
Irreversible cell injury occurs at ~30 minutes.
As ATP is depleted, it is degraded to ADP –> AMP –> adenosine. Adenosine can diffuse out of the cell and cause vasodilation. Following 30 minutes of ischemia, half of cellular adenine stores are gone and thus the cell cannot recover.
What are the inhibitors of dihydrofolate reductase?
Methotrexate - cancer
Trimethoprim - bacteria
Pyrimethamine - malaria & toxoplasmosis
What are the toxicities seen with statins?
Hepatotoxicity (check LFT’s before prescribing)
Rhabdomyolysis
What are the serum/urinary markers of osteoblastic activity?
Osteoclastic?
Osteoblasts - Alkaline phosphatase
Osteoclasts - TRAP, Urinary hydroxyproline, urinary deoxypyridinoline
What organisms show a positive Tzank smear?
Tzanck test = scrapinf of an ulcer base to look for Tzanck cells (multinucleate giant cells) seen in: HSV VZV CMV Pemphigus vulgaris
What are the mechanisms by which combination OCP’s function?
1) Feedback inhibition on the pituitary –> no LH spike
2) Thickened cervical mucus
3) No growth of endometrium –> not suitable for implantation
What is the drug of choice for hypertensive crisis?
Nitroprusside
What is the antidote for nitroprusside overdose?
Sodium thiosulfate
It acts as a sulfur donor to enhance conversion of cyanide –> thiocyanate
How do infantile & adult botulism differ?
Adults ingest preformed toxin, whereas infants ingest spores (honey) that germinate in the gut. Also, infantile is usually less severe.
What is the psoas sign?
What is it indicative of?
Lying on their side, passive hyperextension of the hip causes pain.
A positive psoas sign can be indicative of a psoas abscess or appendicitis (if on the right).
What is the mechanism of INH?
It is a pyridoxine analog that inhibits mycolic acid synthesis in MTB.
What occurs in tissues when a patient has CREST or systemic scleroderma?
Monoclonal T cell proliferation –> cytokine release (especially TGF-beta) –> excessive deposition of collagen by fibroblasts
What vitamin can be used to treat measles?
Vitamin A
They don’t know why, the measles virus may induce a deficiency.
What is the full name of PCP?
What is seen in pts who are on it?
Phencyclidine
Vertical or horizontal nystagmus
Violent behavior
What is the mechanism of Phencyclidine?
PCP is an NMDA antagonist –> ^excitatory NT’s –> hallucinations
How does a glucagonoma present?
Migratory skin necrolysis
Erythematous groin rash
Diabetes
Anemia
What changes are seen in the adrenals in a pt with Cushing disease?
Cushing disease - ACTH must be coming from pituitary adenoma
HyperPLASIA of both the zona fasciculata & reticularis
What is seen with thalamic syndrome?
Thalamic stroke in the VPL/VPM area –> pure sensory stroke causing total sensory loss of the contralateral side of the body.
No motor deficits but impaired proprioception can cause falls.
What is used to create cystathionine?
What cofactor is needed?
Homocysteine + Serine –> Cystathionine –> Cysteine
Both of these steps require Vit. B6
What is the cycle for how THF is regenerated from 5-methyl-THF?
1) Homocysteine + 5-M-THF –> Methionine + THF
(Methionine synthase/Homocysteine methyltransferase)
(Requires Methylcobalamin)
2) Methionine + ATP –> S-adenosyl methionine (SAM)
3) SAM –> S-adenosyl homocysteine
(Methyltransferase)
4) S-adenosyl homocysteine –> Homocysteine
What is the mechanism of echinocandins?
Caspofungin & Micafungin (echinocandins) inhibit polysaccharide (glucan) synthesis –> inhibit fungal cell wall synthesis
What is the mechanism of Griseofulvin?
It enters fungal cells, binds MT’s & inhibits mitosis.
What is seen on liver biopsy in halothane-associated hepatitis?
Massive centrilobular hepatic necrosis
Mortality ~80%
How does Crohn’s disease lead to kidney stones?
Terminal ileum damage –> Bile acids not reabsorbed –> Steatorrhea –> loss of Ca2+ as soaps in stool –> Ca2+ not available to bind up oxalate in the gut –> ^Oxalate absorption –> kidney stones
What is seen on liver biopsy of a patient with Reye’s syndrome?
Microvesicular steatosis
No necrosis or inflammation
What are the effects of Sotalol?
It has properties of a beta blocker & a Class III antiarrhythmic (K+ channel blocker) –> ^PR & ^QT
What groups are at risk for Pellegra?
Populations that subsist on corn Alcoholics Carcinoid syndrome INH Hartnup disease
What is B3 synthesized from endogenously?
Niacin is synthesized from Tryptophan
What causes the outflow obstruction seen in HOCM?
Hypertrophied septum is too close to anterior mitral valve leaflet –> (paradoxical) systolic anterior motion of the anterior mitral valve leaflet –> leaflet moves closer to septum –> outflow obstruction
What drugs display tachyphylaxis?
Topical antihistamines (endogenous NE is downregulated) Nitroglycerine (less NO release)
Both of these drugs require time off in order to maintain their efficacy.
What is the reaction catalyzed by G6PD?
G6P + NADP –> 6-Phosphogluconate + NADPH
What is used to treat TCA overdose?
Sodium bicarbonate
What is the most common toxicity of aspirin?
GI bleeding
This is seen even with low dose aspirin, but especially with high dose.
What is the use of Fomepizole?
Inhibits alcohol dehydrogenase. It is used for ingestion of methanol, ethylene glycol, propylene glycol.
What is seen on esophageal manometry in CREST syndrome?
Decreased peristalsis
Decreased LES tone
What is the mechanism of macrolides?
Tetracyclines?
Macroslides –> elongation
Tetris –> blocks tRNA binding
What causes a Bartholin cyst?
Obstruction of the Bartholin gland with subsequent infection. Seen in women of reproductive age.
Unilateral painful cystic lesion just below the & adjacent to the vaginal vestibule.
What causes condylomas?
HPV 6 & 11 infection
What is seen with Lichen sclerosis?
What is the complication seen with it?
Leukoplakia with parchment-like vulvar skin in postmenopausal women.
Slightly increased risk for SCC.
What is seen with lichen simplex chronicus?
Chronic irritation & scratching –> leukoplakia w/ thick leathery skin
No increased risk of SCC (only lichen sclerosis has ^risk)
What are the causes of vulvar leukoplakia?
Lichen sclerosis
Lichen simplex chronicus
Squamous cell carcinoma
What causes SCC of the vulva?
Two possible etiologies:
1) VIN due to HPV infection
2) Longstanding lichen sclerosis
What causes hemolytic disease of the newborn?
Rh+ infant born to a (sensitized) Rh- mother
ABO type is mild
Rh type is severe but preventable
What is used to prevent hemolytic disease of the newborn?
How does it work?
RhoGAM
They are IgG against the Rh antigen that bind up & eliminate any fetal RBC’s that are passed to mom. This prevents mom from mounting an immune response against the Rh antigen (fetal RBC’s)
What does the posterior descending coronary artery supply?
The posterior walls of the ventricles & posterior 1/3 of septum
What is seen with congenital neutropenia?
Low neutrophil counts at birth or shortly afterward. Severe recurrent infections seen later w/ no pus.
What ventricle is anterior & which is posterior?
The RV is anterior & right border
The LV is posterior & left lateral
What gives cephalosporins their expanded spectrum?
They are less susceptible to beta-lactamases
What are irradiated blood products used for?
To prevent Transfusion-Associated Graft vs. Host Disease
(TA-GVHD)
Blood that is given to immunodeficient patients should be irradiated prior to transfusion.
What cranial nerve innervates the pharyngeal constrictor muscles?
CNX
How does beta thalassemia minor present?
Usually asymptomatic
Diagnosis is incidental by microcytic anemia on CBC
Confirmation is via >3.5% of HbA2 on electrophoresis
How is acetylcholinesterase poisoning treated?
Atropine - reverses central respiratory depression & other symptoms
Pralidoxime - Reverses AChE poisoning
Give both at once
What is the equation for specificity?
Sp = TN /(TN + FP)
Sp = 1 - false positive
What is the equation for sensitivity?
Sn = TP/ (TP + FN)
Sn = 1 - FN
What is a wound contracture?
Excessive activity of metalloproteinases & myofibroblasts can cause a wound contracture, which can lead to deformity or limit the mobility of a joint.
How are cirrhotic patients screened for HCC?
Serum AFP levels are monitored regularly
What causes neonatal tetanus?
Colonization of the umbilical stump
A common occurrence in developing countries.
How does Parvovirus infection manifest in adults?
Arthritis in adults
Erythema infectiosum in children
Describe the mTOR pathway following growth factor binding.
Binding of growth factor –> Autophosphorylation of tyrosine kinase –> Activation of phosphoinositide-3 kinase –> Phosphorylation of PIP2 –> Activation of Protein kinase B –> Acivation of mTOR –> Translocation to nucleus to activity genes
This pathway is active in many cancers. Sirolimus is an mTOR inhibitor.
What causes cardiovascular dysphagia?
Enlargement of the left atrium –> compression of the esophagus
What is the progression of CD4/8 expression of T cells in the thymus?
Double negative –> Double positive –> single positive
How is resistance to INH developed?
Either decreased expression of catalase-peroxidase (required for INH activation) or modification of the mycolic acid synthesis enzyme.
Why is the infectious dose of vibrio so high?
They prefer alkaline environments & are killed easily by acid.
What is the best prognostic factor in meningococcemia?
Blood levels of lipooligosaccharide (LOS)
What is the mechanism of Nystatin?
Binds ergosterol in the cell membrane and creates pores in the membrane –> leakage of ions from the cells –> cell lysis
Same as Amphotericin B
How are enterococci resistant to aminoglycosides?
They transfer chemical groups onto the drug (acetyl, adenyl, phosphate) that impair its binding to ribosomes.
What is Trousseau’s syndrome?
What causes it?
Migratory superficial thrombophlebitis seen with pancreatic, colon, or lung adenocarcinoma.
These tumors can produce a thromboplastin-like (Tissue factor-like) substance.
How is hereditary spherocytosis inherited?
Autosomal dominant
What vitamin deficiency is commonly seen in patients with hemolytic anemia?
Folic acid deficiency
This is because they have increased turnover of cells
Why do Crohn’s disease patients get gallstones?
Bile acids not absorbed in terminal ileum –> Decreased concentration of them in the bile –> Gallstones
What is ANOVA used for?
It is like a T-test for more than 2 populations. It compares the numerical means of multiple populations.
What is the effect of Tetrodotoxin?
Binds to Na+ channels on neurons & prevents them from opening. It is found in puffer fish.
What causes Lymphogranuloma venereum?
What is seen?
Chlamydia trachomatis (L1-L3 serotypes)
1) Initial painless ulcer on genitals
2) Swollen painful inguinal nodes –> rupture (buboes)
Treat with doxycycline
What are the macrolides?
ACE
Azithromycin
Clarithromycin
Erythromycin
What injury is seen following humerus dislocation?
(Anterior) humerus dislocation –> axillary nerve injury
It is the most commonly dislocated joint in the body.
What is the mechanism of Enfuvertide?
Binds gp41 on HIV cell membrane –> prevents gp41 from undergoing conformational change & causing membrane fusion
What are the effects of PPAR-gamma?
Increased synthesis of: Adiponectin Fatty acid transport protein Insulin receptor substrate GLUT4
Where are thyroid hormone receptors located?
In the nucleus. The other steroid hormone receptors are found in the cytosol & translocate to the nucleus upon binding.
What stains can be used to detect cryptococcus neoformans?
Mucicarmine –> red stained polysaccharide capsule
India ink stain –> Clearing around the cell (polysaccharide capsule)
What would the approximate Vd be for these drugs?
Large/Plasma protein bound/Highly charged
Small & hydrophilic
Small & hydrophobic
Large/Plasma protein bound/Highly charged –> ~4L (plasma)
Small & hydrophilic –> ~15L (extracellular fluid & plasma)
Small & hydrophobic –> ~41L (everywhere)
What skin findings can be seen with Pseudomonas?
Ecthyma gangrenosum
Cutaneous necrotic lesions caused by hematologic dissemination & subsequent local release of exotoxins.
What does myelination do to the time constant & space constant?
Space (length) constant is increased (further transmission)
Time constant is decreased (faster transmission)
What is the DOC for combined absence & tonic-clonic seizures?
Valproic acid
What can cause lithium toxicity?
Drugs that affect Na+ handling in the kidney (thiazides)
Drugs that affect GFR (ACEi, NSAIDs)
Volume contraction (CHF, GI bleed, Cirrhosis)
Li+ is handled just like Na+ is handled in the kidney. Thus, anything that could cause Na+ retention can cause Lithium toxicity. Treatment is cessation & hemodialysis.
What embryologic layer do the branchial arches arise from?
Neural crest ectoderm
What are the macrolides?
ACE
Azithromycin
Clarithromycin
Erythromycin
What injury is seen following humerus dislocation?
(Anterior) humerus dislocation –> axillary nerve injury
It is the most commonly dislocated joint in the body.
What is the mechanism of Enfuvertide?
Binds gp41 on HIV cell membrane –> prevents gp41 from undergoing conformational change & causing membrane fusion
What are the effects of PPAR-gamma?
Increased synthesis of: Adiponectin Fatty acid transport protein Insulin receptor substrate GLUT4
What embryologic layer do the branchial arches arise from?
Neural crest ectoderm
What can cause lithium toxicity?
Drugs that affect Na+ handling in the kidney (thiazides)
Drugs that affect GFR (ACEi, NSAIDs)
Volume contraction (CHF, GI bleed, Cirrhosis)
Li+ is handled just like Na+ is handled in the kidney. Thus, anything that could cause Na+ retention can cause Lithium toxicity. Treatment is cessation & hemodialysis.
What is the DOC for combined absence & tonic-clonic seizures?
Valproic acid
What does myelination do to the time constant & space constant?
Space (length) constant is increased (further transmission)
Time constant is decreased (faster transmission)
What skin findings can be seen with Pseudomonas?
Ecthyma gangrenosum
Cutaneous necrotic lesions caused by hematologic dissemination & subsequent local release of exotoxins.
What would the approximate Vd be for these drugs?
Large/Plasma protein bound/Highly charged
Small & hydrophilic
Small & hydrophobic
Large/Plasma protein bound/Highly charged –> ~4L (plasma)
Small & hydrophilic –> ~15L (extracellular fluid & plasma)
Small & hydrophobic –> ~41L (everywhere)
What stains can be used to detect cryptococcus neoformans?
Mucicarmine –> red stained polysaccharide capsule
India ink stain –> Clearing around the cell (polysaccharide capsule)
Where are thyroid hormone receptors located?
In the nucleus. The other steroid hormone receptors are found in the cytosol & translocate to the nucleus upon binding.
What is torticollis?
What causes it?
It is congenital fibrosis of the SCM that causes tilting of the head & contralateral head turn, presenting at 2-4 weeks of age. It is caused by birth trauma or malposition of the head in utero.
It can be treated with conservative therapy & stretching exercises.
What is characteristic of CSF proteins in SSPE?
Oligoclonal bands of Ab’s are found
None are against the M component of measles virus
If patients are loss to follow up, what kind of bias is this?
Attrition bias (a type of selection bias)
What portion of the aorta is most vulnerable to traumatic rupture (i.e. a car accident)?
The aortic isthmus
Just distal to the branch point of the left subclavian, where the ascending & descending aorta meet.
What causes Ménière’s disease?
What is seen?
An increased volume of endolymph –> damage to vestibular & cochlear organs
Triad of:
Tinnitus
Vertigo
Hearing loss (sensorineural)
What is seen on ECG in Wolff-Parkinson-White syndrome?
Recurrent paroxysmal SVT
Baseline ECG:
Shortened PR
Delta wave before QRS
Widened QRS
What type of glands are found in the dermis of skin?
Eccrine (merocrine) - sweat glands
Apocrine - genitals, axilla, areola; secrete onto hair follicles
Sebaceous glands - holocrine secretion of sebum onto hair follicles
What organism causes cat scratch disease?
What is seen?
Bartonella henselae
Self-limited low fever, LAD
Can cause bacillary angiomatosis in immunocompromised patients
What is a test’s reliability?
The same thing as precision. The ability to produce consistent results (whether or not they are accurate)
What are P bodies?
They lie in the cytoplasm & play a role in mRNA translation regulation & degradation.
What are the MAOi’s?
Tranylcypromine
Phenelzine
Selegiline
What type of renal damage is seen with prolonged NSAID use?
Papillary necrosis
Chronic interstitial nephritis
What mutations cause HOCM?
What mutations cause hereditary dilated cardiomyopathy?
HOCM - Autosomal dominant mutations in myosin heavy chain
Dilated CM - Autosomal dominant mutations in cytoskeleton (dystrophin) or mitochondrial enzymes
What is the treatment of diphtheria?
1) Diphtheria antitoxin (passive immunity)
2) Penicillin or erythromycin
3) DPT vaccine
Important to give antitoxin early since it cannot affect toxin that has reached the CNS or heart. Most common cause of death is cardiomyopathy (5-10% mortality).
How can complete vs partial central diabetes insipidus be differentiated?
Response to vasopressin administration:
>50% increase in urine osmolarity –> complete central DI
partial central DI
Partial central DI = some ADH is produced but not enough for normal kidney function.
What antiarrhythmic classes affect PR & what affect QT?
1 and 3 –> long QT
2 and 4 –> long PR
What are the Class I antiarrhythmics?
“Double Quarter Pounder w/ Mayo Lettuce Tomato, and Fries Please”
Ia: Disopyramide, Quinidine, Procainamide
Ib: Mexiletine, Lidocaine, Tocainide
Ic: Flecainide, Propafenone
What causes the chronic myeloproliferative disorders?
CML = t(9;22) –> BCR-ABL fusion protein
Essential thrombocytosis, Polycythemia vera, Primary myelofibrosis = JAK2 mutation –> constitutive tyrosine kinase activity
What anticonvulsant is metabolized to other active anticonvulsants?
Primidone –> Phenobarbital & Phenylethylmalonamide
Primidone can cause lethargy
Anti-histone Ab’s
Drug-induced lupus
What is the most common cause of HCC?
Hepatitis B
Vaccination is important
What do Auer rods stain positive for?
Myeloperoxidase
Seen in myelogenous leukemias
What complications of Herpes Zoster are possible?
Herpes zoster ophthalmicus (if in V1 ganglion) –> visual probs
Post-herpetic neuralgia:
Persistent pain for months after resolution
Increases with ^age
What is the most common cause of death in diabetes?
Coronary heart disease
What is the treatment for malignant hyperthermia?
What is its mechanism?
Malignant hyperthermia is caused by inhaled anesthetics & succinylcholine. Ryanodine receptors release large amounts of Ca2+ into the cytoplasm, exhausting ATP stores in an attempt to pump it back in to the SR.
The treatment is Dantrolene - inhibits Ryanodine receptors to act as a muscle relaxant.
Why is primary hyperaldosteronism not associated with edema?
Aldosterone escape:
1) Pressure natriuresis
2) Increased delivery of sodium to distal nephron overrides aldosterone’s action there
3) ANP
What are the causes of renal artery stenosis?
Atherosclerosis - older person with other atherosclerotic dz
Fibromuscular dysplasia - young woman of childbearing age
Both can cause HTN due to renal artery stenosis. Fibromuscular dysplasia shows a “beads on a string” appearance on angiography.
What is the DDx for malabsorption?
“These Will Cause Lasting Absorption Problems”
Tropical sprue Whipple's disease Celiac sprue Lactose intolerance Abetalipoproteinemia Pancreatic insufficiency
Also infectious causes (giardia, etc.)
What is seen in Whipple’s disease?
“Foamy Whipped cream in a CAN”
Foamy (PAS+) macrophages in SI lamina propria
Cardiac symptoms, Arthralgias, Neurologic symptoms
Most commonly occurs in older men.
What changes are seen in the bowel from celiac disease?
Blunting of villi & crypt hypertrophy in the distal duodenum & proximal jejunum
What complications are seen with celiac disease?
1) Vitamin deficiencies
2) Small bowel carcinoma
3) Enteropathy-Associated T-cell Lymphoma (EATL)
What are the types of chronic gastritis?
Type A - autoimmune (Type IV) against parietal cells
Type B - H. pylori infection
What is seen with Menetrier’s disease?
Gastric hypertrophy (look like brain gyri)
Protein-losing gastropathy
Parietal cell atrophy
^Mucous cells
What cancers are associated with H. pylori infection?
Gastric adenocarcinoma
MALT lymphoma
Esophageal SCC (protective against esophageal adenocarcinoma)
What risk factors are associated with gastric adenocarcinoma?
H. pylori infection (intestinal type only) Smoked foods (nitrosamines) Achlorhydria Chronic gastritis Type A blood
What immune deficiency is seen in celiac patients?
IgA deficiency
If present, must test for IgG against gliadin, endomysium, tTG
What vessel bleeds in a duodenal ulcer hemorrhage?
What is the additional risk?
Posterior wall ulcer –> gastroduodenal artery bleed
This can cause acute pancreatitis!
What diseases are associated with p-ANCA?
Ulcerative colitis
Microscopic polyangiitis
Churg-Strauss disease
What is seen grossly with Crohn’s disease?
Transmural inflammation Cobblestone mucosa Creeping fat Linear ulceration Stricture (string sign on barium x-ray)
What is seen grossly in Ulcerative Colitis?
Mucosal & submucosal inflammation only
Pseudopolyps
Loss of haustra –> lead pipe appearance on x-ray
What is seen microscopically in Crohn’s disease?
UC?
Crohn’s:
Noncaseating granulomas
Lymphoid aggregates
UC:
Crypt abscesses
What conditions are associated with ulcerative colitis?
PSC Toxic megacolon CRC Pyoderma gangrenosum Ankylosing spondulitis Uveitis
What conditions are associated with Crohn’s disease?
CRC Migratory polyarthritis Erythema nodosum Ankylosing spondylitis Uveitis Kidney stones (malabsorption --> Ca2+ excreted in feces)
What is the association between smoking and IBD?
Smoking ^ risk of Crohns
Smoking protects against UC
What is the treatment for Crohn’s disease?
The same as for RA
Steroids Azathioprine MTX Infliximab Adalimumab
What is the treatment for ulcerative colitis?
Sulfasalazine (ASA prep)
6-MP
Infliximab
Colectomy
What can be seen with diverticulosis?
What are the complications?
Usually asymptomatic
Hematochezia
Diverticulitis
Fistulas
What causes pneumaturia?
Diverticulitis –> colovesical fistula
What is seen with a Meckel’s diverticulum?
Persistence of the Vitelline duct, leading to:
Melena
RLQ pain
Intussusception, volvulus, obstruction
Dx: Pertechnate study for ectopic gastric tissue
What causes intussusception?
Children: Viral infection (adenovirus & rotavirus) –> LAD –> leading edge
Adults: Tumor is leading edge
Where do intussusception & volvulus occur?
Intussusception: Ileocecal valve
Volvulus: Children = cecum, Adults = sigmoid colon
How can the RTA’s be distinguished on UA/Labs?
Type 1 (distal) –> hypokalemia, urine pH > 5.5
Type 2 (proximal) –> hypokalemia, urine pH < 5.5
Type 4 (aldosterone) –> hyperkalemic
What is seen in chronic lung transplant rejection?
Bronchiolitis obliterans
The small airways are inflamed & then fibrosed, rather than the vascular beds as in other organ transplants.
How does H. pylori lead to gastric ulceration?
Duodenal ulceration?
Gastric = local inflammation
Duodenal = impaired somatostatin release –> ^gastrin –> ^acid
What cells mediate the fibrosis seen in atherosclerosis?
Smooth muscle cells respond to endothelial injury signals (PDGF). These reactive smooth muscle cells are responsible for intimal hyperplasia & fibrosis.
What signaling molecules mediate atheroma formation?
PDGF (from platelets, endothelial cells, & macrophages)
TGF-beta (from platelets)
What general medical conditions are associated with carpal tunnel syndrome?
Hypothyroidism
Diabetes
Rhematoid arthritis
Dialysis-associated amyloidosis (beta-2 microglobulin)
How does T-ALL present?
Mediastinal mass
It can compress local structures leading to SVC syndrome, dysphagia, or respiratory symptoms. Also the standard symptoms of lymphoma will be present.
What is carnitine used for?
To shuttle fatty acids into the mitochondria for beta oxidation.
What is the capsule of H. flu type B composed of?
Polyribosyl-ribitol-phosphate (PRP)
Antibodies against this protein are associated with immunity against HiB. The vaccine is composed of PRP conjugated to diphtheria or tetanus toxoid.
What are the common dystonias?
Spadmodic torticollis (cervical dystonia)
Blepharospasm (eyes held closed)
Writer’s cramp
What are the Class I antiarrhythmics?
“Double Quarter Pounder w/ Lettuce, Tomato, Mayo & More Fries Please”
Ia:
Disopyramide
Quinidine
Procainide
Ib:
Lidocaine
Tocainide
Mexiletine
Ic:
MORicizine
Flecainide
Propafenone
What patients are at risk for succinylcholine-induced hyperkalemia?
How does this occur?
Burns
Myopathies
Crush injuries
Denervating injuries
Succinylcholine constantly stimulates the AChR (a nonselective cation channel), allowing both Na+ influx and K+ efflux. When open for a long time, this can cause a lot of K+ efflux from muscle cells –> hyperkalemia
What, within the brain, is the cause of the extrapyramidal side effects seen with antipsychotics?
D2 blockade in the nigrostriatal pathway
What causes thigh claudication?
Atherosclerosis of the external iliac or femoral arteries.
What is the most common cause of death by drug overdose?
Opioids
What is the most common elbow injury in young children?
What causes it?
Radial head subluxation (Nursemaid’s elbow)
Caused by a sudden pull on an extended arm that is pronated. The annular ligament slips over the radial head & into the radiohumeral joint. The child will hold his arm in a pronated & extended position close to the body & not want to move it. Reduction occurs by full supination & flexion of the elbow.
What is seen with Theophylline overdose?
Theophylline = a PDE inhibitor & stimulant used for asthma
Overdose:
Seizures
Tachyarrhythmia
What protein is used to secrete conjugated bilirubin into the bile canaliculi?
MRP2
It is an organic anion transporter & is energy-dependent. Uptake of unconjugated bilirubin at the basolateral membrane is passive.
What is Tommy John surgery?
Ulnar collateral ligament reconstruction
This is an injury commonly seen in pitchers due to intense valgus stress on the elbow.
What is seen with Salicylate overdose?
1) Early respiratory alkalosis
2) Late metabolic acidosis superimposed on the early alkalosis, resulting in a mixed acid-base disturbance.
How can E. coli O157:H7 be distinguished from other strains in culture?
Does not ferment sorbitol
Does not produce glucuronidase
How does hyperparathyroidism present histologically in bone?
Subperiosteal thinning
What is seen with Osler-Weber-Rendu syndrome?
Hereditary hemorrhagic telangiectasia
Autosomal dominant disease
Telangiectasias on all mucous membranes
Recurrent mucosal bleeding (epistaxis, GI, hematuria)
What ligaments form the lesser omentum?
Hepatogastric & Hepatoduodenal ligaments
Where does Inhibin B feedback?
Testosterone?
Inhibin B –> pituitary (only)
Tesosterone –> pituitary & hypothalamus
What bacteria is pyrrolidonyl arylamidase positive?
Strep pyogenes is PYR+
It was used before bacitracin to determine if it was GAS or GBS
What is the treatment for hemophilia A?
Desmopressin –> vWF release –> ^Factor VIII levels
What cell type does renal cell carcinoma arise from?
PCT tubular cells
How do benzodiazepines affect the GABA receptor?
Barbiturates?
Benzos - increase frequency of GABA opening
Barbs - increase duration of GABA opening
What are the stages of a lobar pneumonia?
Congestion (24h)
Red hepatization (days 2-3)
Gray hepatization (days 4-6)
Resolution
What is the most common cause of death in TCA overdose?
Refractory hypotension & cardiac arrhythmia due to inhibition of Na+ channels in the heart.
Use NaHCO3 to resuscitate.
What causes unilateral SVC syndrome?
Obstruction of the brachiocephalic vein on one side.
Can be caused by thrombosis or by external compression (tumor, etc.)
What is the function of cord factor?
It is a virulence factor found on mycobacteria
Causes: Neutrophil inhibition Mitochondrial destruction TNF release Also causes linear growth pattern of mycobacteria
What cosmetic side effects are seen with Phenytoin?
Hirsutism Coarse facial features Acneiform skin rash Gingival hypertrophy LAD (pseudolymphoma)
What substances can cause Serine phosphorylation leading to insulin resistance?
TNF-alpha
Glucagon
Fatty acids
Glucocorticoids
What portions of the nephron are most susceptible to ischemic injury?
Proximal tubule & thick ascending limb
What toxicities are seen with NRTI’s?
Bone marrow suppression Peripheral neuropathy Lactic acidosis (Zidovudine, Didanosine, Stavudine) Rash Anemia (Zidovudine)
What drug is used to test for Prinzmetal angina?
Ergonovine
It stimulates both alpha-adrenergic & 5-HT receptors –> spasm
What substances can inhibit iodide uptake at the thyroid gland?
Competitive anion inhibitors:
Perchlorate
Pertechnetate
Also iodide can
What does the stapes transmit vibration to?
The oval window
The round window is the one that just relieves pressure.
What is the helicotrema?
The apex of the cochlea
What processes use NADPH?
Fatty acid, cholesterol, steroid synthesis
Drug metabolism
Antioxidant in RBC’s
What CN’s can be compressed by an acoustic neuroma?
CNV –> paralysis of muscles of mastication & loss of corneal rflx
CNVII –> facial paralysis & hyperacusis
CNVIII —> tinnitus, vertigo
What infections are caused by Pseudomonas?
PSEUDO: Pneumonia (CF) Sepsis (ecthyma gangrenosum) External otitis (diabetics, severe) UTI Drug users Osteomyelitis in diabetics
Sudden vision loss & a pale retina & cherry red macula
Central retinal artery occlusion (CRAO)
At what lung volume is PVR the least?
Why?
At FRC
At high lung volumes, alveolar vessels are stretched longitudinally & narrowed. At low lung volumes, extra-alveolar vessels are not pulled open.
How is Strongyloides infection diagnosed?
Why must it be treated?
Larvae in the stool is diagnostic
Must be treated because it can autoinfect the same host over and over, leading to superinfection.
What step in the TCA cycle requires thiamine?
Alpha-ketoglutarate dehydrogenase
What drugs can niacin interact with?
Potentiates vasodilators (decrease meds) Increases insulin resistance (^meds)
What is the most prominent side effect of Amphotericin B?
Renal toxicity
Patients often require daily supplementation of potassium and magnesium.
What physical exam finding can be used to rule out aplastic anemia?
Splenomegaly
What can cause unilateral nasal hemianopia?
Aneurysm or calcification of the internal carotid. It can compress the lateral side of the optic chiasm.
What drugs (aside from antidepressants) can cause serotonin syndrome when taken with SSRI’s?
Tramadol
Ondansetron
Linezolid
What are the most common causes of primary amenorrhea with normal gonadotropin & hormone levels?
Imperforate hymen
Müllerian duct abnormalities (back of vagina, uterus, fallopian)
What substances require tetrahydrobiopterin as a cofactor for their synthesis?
Serotonin (from tryptophan) NO (from Arg) Tyrosine (from Phe) Dopamine NE/EPI
What antibodies cause idiopathic membranous nephropathy?
Anti-Phospholipase A2 (PLA2)
How is the lac operon regaulated?
^cAMP –> ^transcription (elevated in the absence of glucose)
^lactose –> ^transcription
What enteric pathogens can cause disease with a low inoculum?
Shigella (10)
Campylobacter (500)
Entaoeba histolytic (1)
Giardia (1)
Where does the pentose phosphate pathway occur?
Exclusively in the cytoplasm
What portions of the urea cycle take place in the mitochondria?
Carbamoyl phosphate synthetase I
OTC
What toxicities are seen with mannitol?
Pulmonary edema
Dehydration
Contraindicated in CHF & anuria
How are serotonin syndrome & neuroleptic malignant syndrome different?
NMS - rigidity
5-HT - myoclonus
Otherwise they are pretty similar (hyperthermia, autonomic dysfunction, altered mental status)
What patients is Allergic Bronchopulmonary Aspergillus (ABPA) seen in?
Asthmatics that take steroids
What is seen in neonates who’s mothers had poor glycemic control during pregnancy?
Macrosomia
Hypoglycemia (beta cell hyperplasia)
What are the 3 types of responses that can be seen after frontal lobe injury?
1) Disorganized
2) Disinhibited
3) Apathetic
What is seen with scarlet fever?
Fever
Pharyngitis
Sandpaper-like rash
Strawberry tongue
What artery can be damaged by a broken hip?
Broken hip = fractured femoral head
The medial femoral circumflex artery provides the majority of blood to the femoral head & neck. Injury can cause avascular necrosis of the femoral head.
What is seen histologically with herpes zoster reactivation?
Intranuclear inclusions in keratinocytes
Multinucleate giant cells
What is seen on CXR in acute LV failure?
Cardiomegaly
Pleural effusions
Kerley C lines
Vascular shadowing
What amino acids are the repeats in collagen?
Gly-X-Y
X & Y can be lysine or proline but glycine must be present every 3rd amino acid. Thus, it is the most prevalent.
What drug is used to treat trigeminal neuralgia?
Carbamazepine
What causes methylmalonic acid in the urine?
1) Deficiency in Methylmalonyl-CoA mutase
2) B12 deficiency
When does calcific aortic stenosis become symptomatic?
Normal patient = 70’s
Bicuspid aorta = 60’s
What is seen with shaken baby syndrome?
Bilateral retinal hemorrhages
Subdural hematoma
Where are the hormones produced that are released by the neurohypophysis?
“OPAS”
Oxytocin = Paraventricular ADH = Supraoptic
What are neurophysins?
Proteins that modify ADH & OXY as they are being transported to the posterior pituitary within vesicles. They are released along with the hormones into the hypophysial vein –> systemic circulation.
What deficiencies result specifically in disseminated MTB?
IL-12 receptor deficiency
IFN-gamma receptor deficiency
Patients require lifelong treatment with antimycobacterial agents.
What occurs with heme’s affinity for oxygen when methemoglobin is present?
Methemoglobin cannot bind O2
The remaining ferrous iron in the Hb molecule has a higher affinity for O2, causing a left shift.
What types of cancer can cause nonbacterial thrombotic endocarditis?
Mucinous adenocarcinoma of the pancreas
Adenocarcinoma of the lung
These cancers produce mucin & are associated with a hypercoagulable state. This is the same pathogenesis as Trousseau’s sign.
What are the class III antiarrhythmics?
“AIDS”
Amiodarone
Ibutilide
Dofetilide
Sotalol
What classes of antiarrhythmics can cause torsades?
Class Ia & Class III
What toxicities are seen with Daptomycin?
^CPK levels
Myopathy
What bacteria are beta hemolytic?
Listeria
Staph aureus
GAS
GBS
What cardiac defect is seen in normal adults?
Patent foramen ovale seen in 20-30% of normal adults
Normally held closed by LA»_space; RA pressures
How does multiple myeloma present?
Fatigue (anemia)
Constipation (hypercalcemia)
Bone pain
Renal failure
Where can viridans strep adhere to?
Fibrin
They produce dextrans from sucrose. These aid their adherence to fibrin at sites of endothelial damage.
What sites are affected in GvH disease?
Skin, liver, & intestine
What drugs can be used to prevent tumor lysis syndrome?
IV Fluids
Allopurinol
Rasburicase - recombinant urate oxidase (converts urate to allantoin, which is 10x more soluble)
What gives elastin its elasticity?
Inter-chain crosslinking of lysine residues
This is performed by extracellular lysyl hydroxylase
What is the mechanism of Miravaroc?
It is a CCR5 receptor inhibitor
Prevents viral attachment of HIV
What is Modafinil used for?
As a non-amphetamine daytime stimulant in narcolepsy
It is a CYP450 inducer
What shape are calcium-based kidney stones?
Tetrahedral
envelope
What shape are struvite renal stones?
Coffin lid
What shape are cystine renal stones?
Hexagonal
What shape are urate renal stones?
Rhomboid
What is used to treat bedwetting?
1) Desmopressin
2) Imipramine
What cell surface markers are found on Reed-Sternberg cells?
CD15, CD30
What are the lymphoma translocations?
8urkitt’s = t(8;14)
Mantle ce11 = t(11;14)
Follicular = Fourteen eighteen = t(14;18)
What distinguishes acute leukemia vs chronic leukemia on a bone marrow smear?
> 20% blasts = acute
What translocations in ALL are indicative of prognosis?
t(12;21) –> Good prognosis; seen in children
t(9;22) –> Philadelphia+ ALL; Poor prognosis; seen in adults
What leukemia can present with DIC?
APL
(M3 form of AML)
Auer rods can cause DIC. Thus, it can also occur following treatment.
t(15;17)
APL
Give ATRA
What leukemia infiltrates the gums?
Acute monocytic leukemia
What is “blast crisis?”
When CML accelerates and transforms into AML or ALL.
What causes increased basophils?
CML
What is seen on coagulopathy labs in uremic patients?
Uremic patients (dialysis, etc.) show normal PT, PTT, & platelet counts but an increased bleeding time.
There are dialyzable platelet inhibitory factors responsible for this, thus it will improve following dialysis.
Where are the lung markings?
Anteriorly the 4th rib = horizontal fissure (Right side only)
The 6th rib = oblique fissure
Where is the abdominal neurovascular plane?
Between the internal oblique & transversus abdominus muscles.
All of the deep abdominal wall arteries & nerves lie here.
What artery travels with the recurrent laryngeal nerve?
Inferior thyroid artery
RLN can be damaged during thyroidectomy
What are the K+ sparing diuretics?
Amiloride
Triamterene
Spironolactone
Eplerenone
What drugs lower TG’s best?
Fibrates > Niacin
What drugs lower LDL the best?
Statins > Ezetimibe
What is Diphenoxylate?
What is its use?
It is an opiate anti-diarrheal
It is combine with atropine to prevent abuse (unpleasant anti-cholinergic effects)
What is the treatment for lice (pediculosis capitis/pubis)?
Permethrin
or
Pyrethrin
What coronary artery supplies the pacemaker nodes?
Bundle of his?
The RCA supplies BOTH the SA node & AV node.
The LAD supplies the bundle of his (supplies anterior 2/3 of the interventricular septum)
