1. Normal pH, serum bicarbonate, and Pco2 levels do not necessarily exclude acid-base disorders. Final pH level is determined by the ratio of bicarbonate and Pco2. The terms “acidemia” and “alkalemia” represent only changes in pH, whereas the terms “acidosis” and “alkalosis” denote underlying pathological processes. Acidosis without acidemia and alkalosis without alkalemia can be seen. Remember to draw blood simultaneously for arterial blood gas measurement and for basic metabolic profile to ensure proper interpretation of acid-base disorders.
2. Always calculate the serum anion gap (AG); otherwise, acid-base disorders may go unrecognized. When calculating AG, pay attention to serum albumin values, which will influence AG significantly. For every 1 g/dL decline in serum albumin <4.4 g/dL, a 2.5 mEq/L reduction in AG occurs. In the case of increased AG, the ratio of AG and HCO3— should be calculated (Δ:Δ). The Δ:Δ<1 suggests mixed normal AG and high AG acidosis; Δ:Δ>2 suggests coexisting metabolic alkalosis. Increases in AG can be seen in nonacidotic states, such as metabolic alkalosis and respiratory alkalosis; however, increases in AG beyond 3 to 5 mEq/L are unusual.
3. Check for appropriate compensation to detect occult mixed acid-base disorders. Over- or undercompensation does not occur and is only indicative of another primary acid-base disorder. Any combination of acid-base disorder can occur, except for respiratory acidosis and respiratory alkalosis. In mixed acid-base disorders, therapeutic decisions should be based on the pH level.
4. Compensation formulas include:Expected compensation in metabolic acidosis:
Pco2 = 1.5 x HCO3— + 8 ±2
Expected compensation in metabolic alkalosis:
Pco2 = 0.6 x ΔHCO3—
Acute respiratory acidosis: ΔHCO3— = 0.1 x ΔPco2
Acute respiratory alkalosis: ΔHCO3— = 0.2 x ΔPco2
Chronic respiratory acidosis: ΔHCO3— = 0.35 x ΔPco2
Chronic respiratory alkalosis: ΔHCO3— = 0.4 x ΔPco2
Since you have to remember 4 formulas for expected compensatory changes in respiratory disorders, “1-4’’ can be used for quick recall.
5. The urinary AG (UAG) can be useful to differentiate between gastrointestinal (GI) and renal causes of a hyperchloremic metabolic acidosis. A negative UAG suggests GI loss of bicarbonate (eg, diarrhea); a positive UAG suggests impaired renal distal acidification (eg, distal renal tubular acidosis). UAG is not useful in volume depletion with urinary sodium <25 mEq/L.
6. In early stages of chronic kidney disease (glomerular filtration rate [GFR] <40 mL/min), normal AG metabolic acidosis can become evident, and as the disease progresses (GFR <20 mL/min), high AG metabolic acidosis can be seen. Serum bicarbonate <10 mEq/L and AG >20 mEq/L are unusual in renal failure and may be indicative of coexistent pathological processes, such as ketoacidosis or lactic acidosis.
7. Lactic acidosis that exceeds 4 to 5 mmol/L in a patient with acidosis is considered significant. The lactate level can exceed 12 mmol/L during grand mal seizures. Drug-induced lactic acidosis has been seen with metformin, isoniazid, and some antiretroviral agents.
8. In adults, salicylate overdose results in mixed metabolic acidosis and respiratory alkalosis; in children, only metabolic acidosis is seen.
9. Diabetic ketoacidosis, alcoholic ketoacidosis, lactic acidosis, and chronic renal failure—but not acute renal failure—are much more common causes of serum osmolal gap increases than are ethylene glycol or methanol intoxications. Serum osmolal gap can be seen without metabolic acidosis, for example, with isopropyl alcohol or with mannitol.
10. Serum osmolal gap of ≥25 mOsm/kg, in the absence of evident causes, strongly suggests methanol or ethylene glycol intoxication. Prophylactic therapy either with fomepizole or with ethanol can be initiated to prevent the formation of toxic metabolites while laboratory test results are pending. Once parent compounds are metabolized, the osmolal gap will disappear, but an increased AG will remain; hence, a normal osmolal gap does not necessarily exclude ethylene glycol or methanol toxicity.
10 pearls of Acid base
Immunology nirvana... ahhhh
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Courtesy of David B., whom I consider one of my closest friends and a trusted collegue.
Some ANS pharm review
You can view it here in a better format!
http://docs.google.com/View?id=ddb246wq_9f8qm94
Parasympathetic Nervous System
Cholinoreceptor:
G protein-linked (Muscarinic): CNS, PNS-targeted tissues, vascular endothelium (not innervated by CNS)
- seven transmembrane domains (third cytoplasmic loop is coupled to G proteins)
M1 & M3: Gq everything except heart → activates the IP3, DAG cascade = ↑ Ca2+
M2 & M4: Giα → heart, inhibits adenylyl cyclase activity (inhibit cAMP & Giβ = ↑K+ flux)
Ion channel (nicotinic): “Neuronal” - ANS postganglions, some CNS neurons; “NMJ” - somatic motor fibers innervating muscles
- 4 subunits form cation-selective ion channels→ electrical and ionic changes→ depolarization
*Prolonged agonist occupancy→ "depolarizing blockade" abolishes the effector response→ can produce muscle paralysis
Direct Muscarinic Agonists:
CV: Direct effect = vasoconstriction; masked by NO-mediated vasodilation (requires intact endothelium) → reflex tachycardia
Pulm: Bronchoconstriction, ↑mucus secretion, *exacerbates asthma
GIT: ↑secretions (salivary, gastric, pancreatic & intestinal) & ↑peristalsis (contract longitudinal muscle while relaxing sphincters)
GUT: Promotes voiding: Detrusor contraction, relax trigone & sphincters
Eye: Miosis (iris contraction), Accommodation (ciliary contraction - facilitates aqueous humor outflow)
Secretory: ↑ secretion by thermoregulatory sweat glands (anomalous Muscarinic receptors of SNS)
Choline Esters - poorly absorbed & poorly distributed into CNS
Acetylcholine [Endogenous transmitter] – rapidly hydrolyzed - Affects both Muscarinic & nicotinic receptors
Low Dose: mostly vascular Muscarinic receptors→ NO→ vasodilation→ reflex tachycardia; cardiac effects hidden by baroreceptor response
High Dose: vascular + direct bradycardia (potential atrial flutter) * Can evoke SNS response thru ganglia (see when using Muscarinic antag)
Methacholine - Slightly resistant to AChE - Specific to Muscarinic (methyl group reduces potency @ nicotinic)
Bethanechol - Resistant to degradation by AChE - Specific to Muscarinic (methyl group reduces potency @ nicotinic)
Carbachol - Resistant to degradation by AChE
- Affects both Muscarinic & nicotinic receptors (i.e. can cause endogenous ACh release through ganglionic nicotinic receptors)
Alkaloids
Muscarine - Fungal (4° amine) alkaloid ACh mimetic
- Activates Muscarinic receptors, CNS activity
- Resistant to AChE
- No therapeutic use
Pilocarpine (ophthalmic) – (natural 3° amine) alkaloid ACh mimetic
- Used to treat glaucoma by allowing for fluid drainage from eye & atropine poisoning
- Resistant to AChE
Muscarinic Receptor Antagonists: Block action of ACh/agonists at Muscarinic receptors;
CNS: Minimal effects – Toxic doses→ agitation, hallucinations & coma; often used w/ dopamine precursor in Parkinson’s, also relieves vagal syncope
CV: Tachycardia (blocks PNS tone @ SA node), few hemodynamic effects
Pulm: Bronchodilation & ↓mucus secretion (not as useful as B2 agonists in asthma)
GIT: ↓motility & secretions – useful for mild GI hypermotility, excessive salivation, or as pre-op adjuvant before abdominal surgery
GUT: can cause urinary retention, especially w/ BPH
Eye: Mydriasis (dilated pupils); Cycloplegia (paralyzed ciliary muscle) – good for ophthalmic exam; Acute glaucoma (narrow anterior chamber angle)
Secretory: “atropine fever” - ↓ thermoregulatory sweating (anomalous Muscarinic receptors of SNS); helpful in hyperhidrosis
Contraindications: Glaucoma (especially closed angle), Prostatic hyperplasia, may ↑ gastric ulcer symptoms
3° Amine – Used for effects in eye or CNS
Atropine [Prototype] – reversible (competitive) blockade with relatively long duration of action; non-selective between M1, 2 & 3
- classic antidote to organophosphate poisoning
- “Atropine Poisoning”: dry (as a bone) mouth, mydriasis (blind as a bat), tachycardia, flushed skin (red as a beet), delirium (mad as a hatter)
Treat with Physostigmine or symptom management
Scopolamine - has a relatively long duration of action, better CNS, motion sickness
Homatropine
Pirenzepine - M1-selective (nerves)
Tropicamide
Tolterodine - M3-selective (urinary urgency, frequency & incontinence)
4° Amine – Only peripheral effects, cannot penetrate CNS (due to charge) – NOT used to reverse cholinergic poisoning
Atropine Methyl Nitrate
Methscopolamine
Ipratropium - asthma
Propantheline
Glycopyrrolate
Indirect Cholinomimetics: ACh-esterase inhibitors (also inhibit ButyrylCh-esterase) → amplify effect of endogenous ACh (modifies PNS tone)
Prominent effects on CV, GIT, eye & skeletal muscle; but NO effect on peripheral vasculature
@ NMJ: low conc. → ↑force of contraction; high conc. →depolarizing neuromuscular blockade
Clinical Uses: Atropine or TCA (tricyclic antidepressant) intoxication/overdose
CNS: Mild to moderate Alzheimer’s disease
GIT & GUT: ↑smooth muscle activity – postop ileus, congenital megacolon, reflux esophagitis, neurogenic bladder, urinary retention
Eye: Glaucoma (closed angle) - ciliary contraction →↑ aqueous humor outflow→ ↓intraocular pressure
NMJ: Myasthenia Gravis
Toxicity: SLUDGE = Salivation, Lactation, Urinary incontinence, Diarrhea, Gastrointestinal cramps & Emesis – reversed by atropine (& 2-PAM)
Simple Alcohol Esters (simple alcohols bearing a 4° ammonium group)
Edrophonium – [very short half-life] - Diagnostic Test for myasthenia gravis
Carbamates (carbamic acid esters of alcohols bearing 3° or 4° ammonium group)
* Undergo 2-step hydrolysis (covalent bond formed w/ enzyme is resistant to hydration; inhibition is longer (30 minutes - 6 hours)
Ambenonium (Mestinon)
Carbaryl – high lipid solubility (rapid CNS effects)
Demecarium- Used to treat glaucoma
Neostigmine – (4° amine - permanent charge renders them relatively insoluble in lipids – poor absorption/CNS distribution)
* Used to treat myasthenia gravis, ileus (severe abdominal cramping due to obstruction)
* Has both indirect & direct effects in PNS (inhibits AChE & stimulated Muscarinic receptors)
Physostigmine – (3° amine - well absorbed, CNS distribution); duration of effect is determined by stability of inhibitor-enzyme complex
- Used to treat glaucoma, myasthenia gravis & atropine overdose
Pyridostigmine - Used to treat myasthenia gravis
Organophosphates - well absorbed topically w/ good CNS distribution (except Echo); * Before aging, pralidoxime (2-PAM) can restore enzyme fxn
bind→ hydrolyzed/phosphorylated AChe active site – extreme stability (strengthened by “Aging”) → lifetime inhibition
Diisoprophylfluorophosphate (DFP) - Can cause cumulative overdose due to extremely long duration of action
Donepezil
Echothiophate – poorly absorbed, very long half-life (~100 minutes) - Used to treat glaucoma
Isoflurophate (ophthalmic) - Used to treat glaucoma
Malathion – [irreversible] - converted to phosphate derivative, used as insecticide
Parathion – [irreversible] – converted to phosphate derivative (Active only after biotransformation), used as insecticide
Sarin
Soman - Immediately & completely binds AChE (no aging) - Potential biological weapon
Tacrine - anticholinesterase and cholinomimetic actions – used for mild/moderate Alzheimer’s disease
Cholinesterase Regenerator
Pralidoxime (2-PAM)
Direct Nicotinic Agonist: Mostly targets ganglia; ↑SNS & PSNS: predominant tone determines effect (SNS = vasculature, PSNS = everything else)
Toxicity: CNS stimulation→ convulsion, coma, resp arrest (NMJ depolarization block); HTN & arrhythmias – Tx w/ Muscarinic Antag. & mech. resp
Nicotine – (natural 3° amine)
Lobeline – (natural 3° amine) a plant derivative similar to nicotine
Ganglion-Blockers (Nicotinic Antagonists): Block action of ACh/agonists at nicotinic receptors in SNS & PSNS ganglia; All are synthetic amines
Blocks homeostatic reflexes (e.g. baro & sweating), but effector cell receptors are NOT blocked; End-Organ effects depend on predominant ANS tone
CV: ↓SNS tone→↓BP & orthostatic hypotension (no baro); ↓PSNS tone @ SA node→ mild tachycardia
GIT: ↓PSNS tone→↓secretions & motility→ constipation & xerostomia (dry mouth)
GUT: Hesitancy or urinary retention (esp. with Prostatic hyperplasia); Impaired sexual function (requires both SNS & PSNS)
Eye: ↓PSNS tone→ cycloplegia (paralyzed ciliary muscle) & moderate pupil dilation (Normal Input: PSNS>SNS)
Tetraethylammonium (TEA) [prototype] - short half-life; used to manage HTN
Hexamethonium
- No therapeutic use currently
Mecamylamine – readily enters CNS→ sedation, tremor, choreiform movements, mental aberrations
Trimethaphan (IV) – 4° Amine →lacks CNS effects
- Extremely short acting
- Can be used to treat acute dissecting aneurysm or autonomic hyperreflexia
Sympathetic Nervous System
Adrenergic Neuron Blockers:
Reserpine - non-selective blocker of uptake & storage of amines
Guanadrel - similar to reserpine
Adrenoreceptor Agonists:
A1- forms IP3, DAG & activates phospholipase C; A2 - presynaptic autoregulation of SNS outflow, inhibits cAMP formation
B1 & B2 - activates adenyl cyclase;
CV: A1→ vasoconstriction, ↓renin secretion; B1 – Ca++ influx into cells (↑ino & chronotropic), ↑renin secretion
Pulm: A1in vessels of URT mucosa→ contraction→decongestion
GIT: A2→↓PNS tone on enteric system; Beta on smooth muscle mediates relaxation
GUT: A1→contract bladder base & urethral sphincter; B2→relax bladder wall smooth muscles – both actions promote urinary retention
Eye: Alpha→ radial dilator contraction→ mydriasis (dilated pupil); Beta→↑aqueous humor production by ciliary epithelium→ ↑intraocular pressure
Exocrine: A1 on aprocrine (stress) sweat glands→ sweating on palms, brow & upper lip
Metabolic: A2→↓ insulin release; Beta→ ↑lipolysis, ↑glycogenolysis, ↑glucose release, ↑insulin secretion
Toxicity: Extended effects – hypertension, tachycardia, CNS – restless, tremor, insomnia, anxiety, paranoia
Catecholamines:
Epinephrine – A1, A2; B1, B2: skeletal muscle arteriodilation & ↑venous capacity (mixed TPR effects)
Norepinephrine - A1: ↑TPR, A2; B1: Heart effects overcome by vagal reflex; = ↑Sys, Dias; High doses = ↑HR
Isoproterenol - B1= ↑CO; B2: skeletal muscle arteriodilation & ↑venous capacity = ↓Dias & MAP
Dolbutamine (B1; A1 @ high doses) - Uses: Heart failure/cardiac decompensation (short-term) – limited by tolerance/desensitization
Dopamine - D1 stimulates adenyl cyclase in renal vasculature→ renal vasodilation→ ↑GFR; A1; B1 @ high doses
Alpha-1 Specific – mydriasis (fundoscopic exam) & decongestant, can ↑BP;
Uses: nasal congestion, hypotension, paroxysmal atrial tachycardia
Phenylephrine [prototype] – not a catechol derivative, thus not inactivated by MAO/COMT; longer duration of action
Methoxamine
Oxymetazoline & Xylometazoline – used as topical decongestants
Alpha-2 Specific – Use as anti-HTN
Clonidine
Methyldopa
Guanfacine
Guanabenz
Beta-1 Specific – ↑CO w/ less reflex tachycardia;
Dolbutamine
Prenalterol (partial)
Beta-2 Specific – bronchodilation; Uses: Asthma & bronchial constriction
Albuterol
Salmeterol
Terbutaline
Ritodrine - uterine relaxation in premature labor
Indirect Sympathomimetics:
Ephedrine – first orally active
Pseudoephedrine [also direct] – cause release of endogenous NE; widely available OTC decongestant
Cocaine - block uptake1 (potentiates effects of NE) - Used as local anesthetic
Tyramine – enter thru uptake1, displace stored catecholamines→ hypertensive crisis; potentiated by MAO inhibitors * fermented foods (cheese)
Amphetamine (NOT a catecholamine) – mech=same as tyramine; ↑mood & alertness; ↓appetite *Common Drug of Abuse – Used for narcolepsy
Methamphetamine – similar, but w/ ↑ratio of central to peripheral effects
Methylphenidate - used to treat ADHD
Adrenoreceptor Blockers:
Alpha Receptor Antagonists - * Nitrates are preferred in hypertensive crises
Non-selective Alpha Antagonists
Phentolamine [prototype] – reversible, competitive; ↓TPR & MAP→reflex tachycardia
Tolazoline – similar to phentolamine;
Phenoxybenzamine – irreversible, slightly alpha-1 selective; Uses: Pheochromocytoma, limited by postural hypotension & reflex tachycardia
*Excessive release of NE & Epi from adrenal medulla
Alpha-1 Selective Antagonists: Uses: HTN & BPH - ↓TPR & BP, May cause postural hypotension & reflex tachycardia
Prazosin
Terazosin
Trimazosin
Doxazosin – longer half-life
Tamsulosin & Alfuzosin – competitive; Uses: BPH (prostate subtype selectivity)
Labetalol - also non-specific beta blocker
Alpha-2 Selective Antagonists
Yohimbine - no established clinical role, has been used in ED
Beta Receptor Antagonists – well absorbed orally
CV: ↓SNS tone to heart → slower AV conduction & ↓BP, but NOT hypotension; ↓SNS tone to kidney→ ↓renin secretion
Pulm: B2 block→ ↑airway resistance
Eye: ↓aqueous humor production by ciliary epithelium→ ↓intraocular pressure
Metabolic/Endocrine: ↓SNS stimulation of lipolysis & glycogenolysis; Use with caution in IDDM patients; Chronic use→ ↑VLDL & ↓HDL
Clinical Uses: HTN (w/ diuretic or vasodilator);
Ischemic Heart Disease - ↓angina frequency, cardiac work/oxygen demand; improves exercise tolerance; prolongs post-MI survival
Cardiac Arrhythmias (atrial & ventricular) - ↑AV refractory period, ↓ventricular response in A-fib, ↓ventricular ectopic beats
Glaucoma – refer to Eye above, better tolerated than Epi or Pilocarpine in open-angle glaucoma
Hyperthyroidism – limits excessive catecholamine activity
Toxicity: Minor= F, rash, depression, sedation; Major= exacerbates asthma, cardiac decompensation, supersensitivity (taper), hypoglycemia in IDDM
Non-selective Beta Antagonists - used to treat: HTN, angina, arrhythmias, glaucoma, and migraine; do NOT use in asthmatics
Propranolol [prototype] – extensive hepatic (first-pass) metabolism, low bioavailability
Nadolol – very long duration of action
Timolol – very long duration of action
Partial Agonists – may prevent bradycardia, changes in lipid profile & precipitation of asthma
Dichloroisoproterenol – first beta-blocking drug
Pindolol
Cartelolol
Penbutolol
Labetalol – reversible alpha-1 antagonist; → hypotension w/ less tachycardia than alpha-blockers
Beta-1 Selective Antagonists - treat HTN; Can also ↑airway resistance when used in asthmatics
Metoprolol
Esmolol – rapid hydrolysis by esterases in RBCs: half-life = 10 min.
Atenolol
Acebutolol – intrinsic sympathomimetic effects
Betaxolol
Bisoprolol
Beta-2 Selective Antagonists
Butoxamine - no clinical use
Pathology
Short post to keep you busy over the weekend!
Good luck everyone!
http://spreadsheets.google.com/pub?key=pp596LBw4L1OLWFbYaPSGaA&output=html
Make your micro list and check it twice...gonna find out who's naughty & nice! :)
Micro is heavily tested on THE test. Knowing how to differentiate bugs and their virulence factors, how they cause disease and their presentations is critical to scoring well on Step 1. This little list is courtesy of a classmate of mine, Kallie. She used to come up with some of the best ways to re-organize material into concise, manageable bites. Thanks Kallie!
I used this list as I prepared by taking it with me on walks at night and focusing on a few of them, making notes to the side and really getting to know micro. I probably answered 15 questions based just on the info here. It enabled me to narrow down and zero in.
Some Classification Lists
Mimics Appendicitis
Yersinia entericolytica
Salmonella typhi
Cause Fever (same as those that invade host tissues)
EIEC
Shigella
Salmonella enteridis (1/2 the time)
Salmonella typhi
Yersinia
Campylobacter jejuni
Listeria
Survive at Cold Temperatures
Yersinia
Listeria monocytogenes (4C!)
Survive at Hot Temperatures
Campylobacter (42C)
Invade Intestinal Epithelium
Shigella
EIEC
Salmonella enteritidis
Listeria
Invade Lymph Nodes, Bloodstream (systemic sx)
Salmonella typhi
Yersinia
Campylobacter jejuni
Bloody Diarrhea (the invaders!)
Salmonella typhi
Yersinia
Campylobacter
EHEC (does not invade, uses Shiga toxin)
EIEC
Shigella
Gram Positive
--- 6 cause disease
Cocci
Streptococcus
Staphylococcus
Rods
Spore-forming
Bacillus
Clostridium
No Spores
Corynebacterium
Listeria (make endotoxin)
Facultative Intracellular Organisms
Listeria monocytogenes
Salmonella typhi
Yersinia
Non-mobile
Shigella
Only G+ w/ Endotoxin
Listeria monocytogenes
Human = Only Host
Salmonella typhi
Shigella
Bactericidal Antibiotics
penicillins
fluoroquinolones
vancomycin
metronidazole
aminoglycosides (can be both –cidal, -static)
Bacteriostatic Antibiotics
tetracycline
sulphonamides
trimethoprim
chloramphenicol
macrolides
lincosamides
aminoglycosides (both)
Facultative Anaerobes
Staphylococcus (G+)
Listeria (G+)
most G- rods
Mycoplasma
Microaerophilic Bacteria
Streptococcus (G+)
Spirochetes (G-)
Campylobacter (G-)
Obligate Anaerobes
Clostridium (G+)
Bacteroides (G-)
Lactose Fermenting
E. coli
Non-Lactose Fermenting
Shigella
Salmonella typhi
Yersinia
V. cholera
Produces H2S
Salmonella typhi
Sterols in Cell Membrane
Mycoplasma
Not a Normal Part of Flora
Shigella
Salmonella
No Cell Wall
Mycoplasma
Stain Acid-Fast
Mycobacteria
Visualize via Darkfield Micro
Spirochetes
Shiga Toxin (AB)
Shigella
EHEC
EIEC
LT
ETEC
V. cholera (cholera toxin)
Campylobacter jejuni
ST
ETEC
EAEC
Yersinia
Resistance Encoded by Plasmid (modify antibiotic, efflux pump?)
Vancomycin (D-ala-D-ala D-ala-D-lactose)
Aminoglycosides (modify drug)
Tetracycline (efflux)
Macrolides, Erythromycin (methylation of rRNA)
Sulfonamides (altered permeability)
Resistance Encoded by Chromosome (altered target, altered permeability?)
Quinolones (altered DNA gyrase, topo IV)
Sulfonamides (altered dihydropterate synthase)
AB Toxin
Shiga
E. coli (LT toxin)
V. cholera
TTSS
EHEC
Salmonella
Shigella
Yersinia
HUS
EHEC
Shigella dystenteriae
Invade M Cells
Yersinia
Shigella
Listeria
Endocrine... Challenging & Important
Endocrine
Multiple Endocrine Neoplasia I
- parathyroid- primary hyperparathyroidism
- pituitary- adenomas
Multiple Endocrine Neoplasia II
- parathyroid hyperplasia
- medullary carcinoma of thyroid
- pheochromocytoma- adrenal medulla tumor
Pituitary
Anterior lobe- hormone producing (all the troph cells)
- corticotrophs- ACTH, MSH
Posterior lobe- hormone storage
- supraoptic nucleus- ADH
- paraventricular nucleus- oxytocin (stimulates uterine smooth muscle, lactation)
Anterior Lobe Hyperpituitiarism
Major Cause
- Pituitary Adenoma-
o Benign, uniform cells, stain uniformly
o pituitary apoplexy
o can eventually lead to hypopituitarism if destroy enough of the gland
o MEN I
o Common Types
Prolactinomas- most common
• Treated surgically, and w/ bromocriptime-
• See calcium deposits mico w/ uniform staining
Growth Hormone Adenoma (of somatotrophs)
• GSP oncogene
• Prolactin can be present sometimes
• GH can cause hyperglycemia
o (side note- both GH and cortisol cause hyperglycemia)
• kids- giantism
• adults- acromegaly
Corticotroph adenoma
• ACTH- cushing DISEASE
o Remember: cushing disease involves pituitary, cushing syndrome involves ACTH hypersecretion outside of pituitary
• Nelson syndrome- cushing symptoms, remove adrenal gland, persistant signs of hyperpigmentation- due to MSH of corticotroph adenoma
Anterior Lobe Hypopituitarism
- pallor
- Causes
o Tumors
pituitary carcinoma
• non functional, only diagnosed when metastasize
rathke's cleft cyst
• benign, ciliated cuboidal epithelium, remove surgically
suprasellar tumors- can grow and squish the pituitary
• gliomas
• germinomas: germ cell tumor, midline, look like gonads histologically, Japanese men, AFP elevated
• craniopharyngiomas: benign aggressive remnants of rathke's pouch
o kids: endocrine prob, adults:visual prob (optic chiasm)
o adamantinomatous: wet karatin, calcifications, cholesterol rich fluid in cyst
o papillary: no cystic, keratin, or calcification
o remove surgically
o ischemic necrosis
Sheehan syndrome: ant gland hyp during pregnancy, hypoperfusion postpartum, post gland more resistant
Other causes…results in ischemic necrosis
o empty sella syndrome
o Apoplexy- hemorrhage
o Hypothalamic disease- sarcoidiosis, TB
o Congenital Hypopituitarism- Pit-1 mutation
Posterior lobe syndromes
- ADH
o diabetes insipidus: impaired ADH, excessive urination
o syndrome of inappropriate ADH secretion- excessive ADH, hyponatremia (because resorption of escessive amounts of free water), increased in total body water, but blood volume stays the same
- oxytocin- no clinical symptoms
Adrenal
Cortex: zones GFR, products-sweeter as you go deeper
- glom- mineralocorticoids- aldosterone- controlled by angiotensin
- fasc- glucocorticoids- cortisol
- retulari- estrogen/androgen
o G/R- controlled by ACTH
o So remember, ACTH hypersecretion will only affect cortisol, estrogen
Diseases of Cortex
- Hypocorticism
o Acute
Waterhouse-Friderichsen syndrome
• Usually~ neisseria meningitis (meningococcus)- will see bacterial CSF
• Hypotension
o Red infarct of adrenal gland
• Schwartzman syndrome- breakdown of platelets, accumulation of fibrin- leads to DIC---
o diffuse petechial hemorrhages
o fibrin clumps in glomerulus of kidney
o chronic
Addison's disease
• Hypoglycemia, hyponatremia
• Focal hyperpigmentation- b/c high ACTH due to loss of cortisol neg feedback and ACTH stimulates corticotrophs to produce MSH- melanocytes
• Mostly idiopathic ATROPHY (lymphocytes), OR caused by TB-adrenal granulomas
• Feared complication: Adrenal Apoplexy- adrenal "collapse"---treat w/steroids
- Hypercorticism
o Cushing Syndrome: elevated cortisol
Hypernatremia, hypophos, increased gluconeogenesis---leading to diabetes, lymphopenia/eosinopenia- cortisol depresses lymphocyte generation
Trunkal obesity, buffalo hump, round face
Causes
• Iatrogenic-corticosteroid therapy
• Pituitary--cushing's Disease
• Adrenal cortical adenoma/carcinoma/hyperplasia
• Ectopic ACTH- lung, etc
Congenital Adrenal Hyperplasia
o 21 hydroxylase deficiency- shunts pathway to testosterone
o clitoral/penile enlargement
o hyperplasia in ZONA RETICULARIS (b/c excessive testosterone prod)
o treat- give cortisol
- Conn's syndrome (hypermineraloadrenocorticism)
o Increase in aldosterone (mineralcorticoid) W/O increase in cortisol (glucocort)
o Hypertrophy in zona glomerulosa
o Clinical: severe HTN, loss of renal K+, sodium retention
o Causes
Cortical adenoma: which is a treatable form of HTN
Nodular cortical hyperplasia/adrenocortical carcinoma
Diseases of Medulla
- Neuroblastoma: adrenal MEDULLA tumor
o Kids,
o abdominal mass, hemorrhagic tendencies, increase in urine VMA
o tumor secretes epi/norepi, histo forms rosettes
o Better prog in kids 1 year- because will progress to ganglioneuroma- benign form
- Pheochromocytoma: neoplasm of chromaffin cells
o 30-50 y/o
o secrete epi/nor epi
o MEN II- medullary cancers of thyroid and adrenal glands
o UNILATERAL, benign, will show HTN and increase in VMA
Thyroid
- Thyroid hormone
o Uncouples oxidative phosp: decrease ATP, greater heat release
o Increase
Cardiac output and SYSTOLIC blood pressure (will cause a widened pulse pressure)
GI motility
O2 consumption----atrophy, spastic muscle
Hyperthyroidism
- Grave's disease
o Ab to TSH receptor-autoimmune
o Diffuse goiter, hyperthyroidism, exopthalmos (not due to inc. TSH, doesn't recede when treat Grave's disease)
o More females
o Clin: increase in systolic blood pressure, heat intolerance, diffuse non-nodal thyroid enlargement, red color
o Maj complications
Exopthalmos
High output heart failure
Thyroid storm- collapse, heart failure shock
Hypothyroidism
- Cretinism- kids: tongue, short, mental retardation
- Myxedema- adults: periorbital edema, NON-PITTING EDEMA, infiltration of glycosaminoglycans into subcutaneous tissue
Thyroiditis- inflammation of thyroid
- Hashimotos
o females
o Autoimmune: Ab to thyroblobulin in colloid (anti microsomal Ab in follicle cells)
o Thyroid enlargement due to Lymphycyte infiltration
o hypothyroid
- subacute (granulomatous, deQuervains)
o formation of granulomas in thyroid
o usually ~ post febrile/viral illness- usu. self-limiting
- Riedel's struma (chronic, woody)
o Heavy fibrous infiltration of thyroid, must distinguish from cancer
Thyroid Tumors
- Benign colloid goiter
o Euthyroid fxn
o Non-uniform nodular enlargement w/ non functional enlarged follicles of colloid
- Benign Adenoma of Thyroid
o Mass w/capsule…capsule keeps it benign
o Microscopic- follicular adenoma
- Thyroid carcinoma
o Papillary- most common, best prog
NO CAPSULE, papillary formation, diffuse
o follicular carcinoma-
probably a follicular adenoma that invaded a capsule..remnants of capsule present with evidence of invasion (capsules and blood vessels)
bad prognosis---metastasizes to bone marrow
- Giant Spindle Cell carcinoma of thyroid
o BAD prog- 6 mo to live
o Rapidly growing- can compress trachea
o Contains BOTH Spindle cells and malignant giant cells
Parathyroid
- chief cells- secrete PTH
- waterclear cells (vasserhelle cells)- chief cell at different stage of secretion
- oxyphil cells- red granules, cytoplasm full of mitochondria
- parathyroid hormone: stim by low calcium
o increase Ca2+
indirect osteoclast resorption (via RANK-L)
stimulates 1 hydroxylation of 1, 25 Vit D in KIDNEY
o decrease phos via decreasing renal tubular resorption of phosp
urine PO4 up, serum PO4 down
o increase in alkalinephosphatase- b/c stim osteoclasts
- calcitonin- from parafolicular cells of thyroid, stim by high calcium
o direct inhibition of bone resorption
Diseases
Hypercalcitonin
- Medullary Carcinoma of thyroid
o tumor secreting calcitonin
o low calcium, high phosphate
Hyperparathyroidism
- symptoms
o resorption of distal phalanges
o high Ca2+, high alk phos
o osteitis fibrosa cystica- bone loss with Ca2+/phos release, anchovy paste
o metastatic calcification of kidney- via calcium phos
- Primary hyperparathyroidism: arising in parathyroid gland---high Ca2+, low phos in serum
o PT adenoma- benign, main cause, uniform chief cells
o PT hyperplasia- clear cell hyperplasia
o PT carcinoma- rare
- Secondary Hyperparathyroidism
o Chronic Renal Disease- big sign…high PTH, low Ca2+, high phos in serum
o Defective Vit D formation-impairs Ca2+ absorption
o Low serum Ca2+- chronic PTH secretion- diffuse hyperplasia of PT glands
o High serum phosp- b/c kidney can't effectively excrete phosphate even when PTH stimulates it to
NON-PTH Hypercalcemia
- coma is main cause of death
- high calcium, NORMAL PHOSPHATE (b/c not PTH induced)
- usu due to variety of tumors (lung, breast)
- malignant cells secrete PTH-Related Peptide
Hypoparathyrodism
- symptoms-
o hypocalcemia: tetani, hyperreflexia
o hyperphosphatemia
- causes:
o accidental removal of PT gland during surgery, Di George, autoimmune,
o pseudohypoparathyroidism
end organ resistance
hereditary- short stature, short neck, rounded face, short fingers
hyperplastic parathyroids (b/c PTH keeps trying to secrete/cause changes)
How 'bout a little Lung Pathology
Good evening all! I'm trying to give some quick-hit reading and "to know" for those preparing for USMLE Step 1. This will continue for a couple more weeks. Most of those who will be taking this exam will be completing their preparation during the next 3 weeks and then entering the wards, where I could then become their intern when they rotate through their internal medicine clerkship at the University of Kansas. That is when the fun begins. Right now, it is time to focus on preparing to take THE test that either opens or closes future doors of opportunity. Sadly, this exam does weigh that heavily.
All of you preparing for this exam and have scheduled to take it in the middle to late June should be doing lots and lots of questions from a question bank, such as USMLE world or Kaplan. I would also recommend as you go back through your question bank to have your FirstAid book handy and write in the margins those explanations that really make it stick for you.
You should have or should be thinking about taking a full, mock exam. This will build your stamina for THE day and make you work that recall muscle I blogged about earlier this month.
Build your confidence, daily! Know you are in the right place, at the right time to do well.
Make sure you are exercising and eating right.
Make a plan, do your plan, believe in your plan and execute!
Alright... enough soap box stuff. As important as it is, here is some lung path to work your brain over.
Make sure to inhale! ;)
Interstitial Lung Diseases
Acute Lung Injury- rapid onset, short duration
- Diffuse Alveolar Damage (DAD)- specific cause, rapid progression-infiltrates
- Acute Interstitial Pneumonia (hamman-rich disease)- like DAD, only no specific cause, fulminant course- need biopsy
o The above two present with pretty severe respiratory symptoms
- Bronchiolitis Obliterans (BOOP)- only one with a good prognosis, air space disease- fibroid polyps filling airspaces
o Presents with fever, cough, dyspnea, bilateral infiltrates
Chronic Interstitial Pneumonia
- Usual Interstitial Pneumonia- varying histology- fibrosis, inflammation
o Infiltrates periphery, base
o Worse prognosis, older people 55
- Desquamative Interstitial Pneumonia- uniform, macrophages in airspace
o Better prognosis---younger 45
Honeycomb lung- dilation/mucous filling air spaces/cyst formation/obliteration of small airspaces to create big ones---end stage
- Acute lung injury- DAD
- Chronic- BOTH UIP, DIP
- Asbestos
- Interstitial glanulomatous diseases
- Eosinophillic granuloma
Hypersensitivity Pneumonitis= Extrinsic Allergic Alveolitis
Non-Necrotizing Granuloma: Hypersensitivity Pneumonitis
Necrotizing Granuloma: Wegener's granulomatosis
Cyclophosphamide
- UIP
- Wegener's Granulamatosis
Diffuse Pulmonary Hemorrhage Syndromes
- Goodpasture's Syndrome---young males, kidney too
o Hemorrhage in intraalveolar spaces
- Vasculitis assoc- both have good prognosis with treatment
o Wegener's granulomatosis-- 50 y/o males, kidney too--mostly other organs
Necrotizing granuloma in lung and vasculature (necrotizing vasculitis)
C-ANCA
o Chrug-Strauss- ASTHMA, P-ANCA, RARE kidney: skin, nerves, heart, looks like eosinophilic pneumonia
Pulmonary Eosinophilia
- eosinophills in BLOOD or SPUTUM…NOT IN LUNG TISSUE ITSELF
- DISEASES:
o Churg-strauss (see above)
o Eosinophilic pneumonias
Simple- LOEFFLER'S SYNDROME- transient infiltrates
Tropical- filiarial
Chronic- only one that needs biopsy, assoc w/ASTHMA
• Responds well to steroids, lots of diff causes
o Allergic bronchopulmonary aspergilliosis- NO BIOPSY
Hypersens to aspergillius (acute branching hyphae)
Ab to aspergillius, central bronchiectasis (dilation)
Immune, not infectious- treat w/ steroids
Pulmonary Eosinophilic Granuloma (histiocytosis X)
- is NOT A PULMONARY EOSINOPHILIA!!!!!!!!
- the eosinophils are located in the lung tissue, NOT the peripheral blood/sputum
- histocyte proliferation, with a pneumothorax (air in pleural cavity)
- langerhans cells w/ bierbeck granule(ovoid nucleus with central line, stain with S-100) CD 1+
- treatment: stop smoking, corticosteroids
Diseases associated with ASTHMATICS- all have pulmonary eosinophilia (makes sense)
- Churg-Strauss
- Chronic eosinophilic pneumonia
- Allergic bronchopulmonary aspergilliosis
Immunologic lung diseases
- Goodpastures
- Allergic bronchopulm aspergilliosis
Sarcoidiosis- multisystem granulomatosis disease
- multiple non caseating, non necrotizing granulomas, usu along lymph pathways (different from TB- which would caseate)
- black, female, 20-40 y/o
- bilateral infiltrates, hilar lymphadenopathy
- increased serum angiotensin converting enzyme
- increased 24 hour calcium secretion
Necrotizing Granulomas along blood pathways- Wegener's granulomatosis
Non-necrotizing granulomas along lymph pathways- sarcoidiosis
Pneumonconiosis
- non-neoplastic rxn in lung to inhaled mineral/organic dust
- Asbestos Diseases
o Asbestosis- pulmonary parenchymal interstitital fibrosis
o Pleural plaque
o Pleural effusion
o Bronchogenic carcinoma
o Malignant mesothelioma
o Laryngeal/extrapulmonary neoplasms
Lung Biopsies
- OLB- gold standard
- VALB- not good for central biopsy
- TBB- good for sarcoid, cancer, infections
o Bad for UIP, DIP
COPD/PFT
Chronic Obstructive Diseases
- Chronic Bronchitis
- Emphysema
o Above two are usually considered COPD
- Asthma
- Bronchiectasis
Chronic Bronchitis
- middle ages, smokers, males
- hallmarks:
o hypertrophy/hyperplasia of submucosal glands (ried Index)
RIED index- meas ratio of submucosal gland thickness to thickness of bronchial wall..>0.4 is bad
o goblet cell metaplasia in bronchi
Remember----terminal bronchiole---respiratory bronchiole---alveolus
Emphysema: enlargement of airspaces, distal to terminal bronchiole
- pathogenesis: protease/antiprotease balance
- defined in morphologic terms
- males, smoking, 50-80 y/o
Types
- centrilobular: most common, resp bronchioles, UPPER lobes
- panlobular: involves BOTH resp bronch and alveoli (whole acinus), LOWER lobes
o alpha-1-antitrypsin defiency (PiZZ genotype)
- localized - (paraseptal), enlargement distal acinus, upper lung, usu asymptomatic
o young adults- spontaneous pneumothorax
- Irregular (paracicatricial emphysema)- fibrosis
- Bullous- occurs w/ other emphysemas
Asthma:
- smooth musc contraction, mucous secretion, increased vascular permeability-edema---leads to bronchial obstruction
- thickened bronchial basement membrane of bronchioles, hypertrophy of bronchial smooth muscle, mucous plugs
Bronchiectasis
- irreversible dilation of bronchi- due to elastic/muscular elements in wall
- Immotile cilia syndrome
o Inherited non-obstructive cause
o Includes Kartagener syndrome: dextrocardia, bronchiectasis, sinusitis, rhinitis, nasal polyps, otitis media
Non Productive cough: Asthma
Productive Cough: bronchiectasis (mucopurulent sputum)
Middle Aged men
- UIP
- DIP
- Hypersensitivity pneumonia
Pulmonary fxn tests
- when have pulmonary function tests: the percent predicted is the "percentage that the "ideal" predicted value that the patient has achieved
- Forced Expiratory Flow :slope of line through volume/time graphs
o FEF 25-75%- small airway disease
o FEF 200-1200- large airway disease
Infectious Lung Diseases
Productive Cough: Bacterial Pneumonia
Bacterial Pneumonia
- Community Acquired Pneumonia: mild- bad if co-morbidities
- Nosocomial
- Opportunistic
- Abscess is complication of bacterial pneumonia
Viral Pneumonia: usu kids, immunocomp
- chronic interstitial pneumonia- lymphocytes
- diffuse alveolar damage- hyaline membranes
- Cytomegalovirus
o Immunocomp,
o Fever, non productive cough, diffuse infiltrates
o Intranuclear inclusion bodies, intracytoplasmic inclusions
Pneumocystis Pneumonia
- immuno comp
- fever, dry cough,
- inter-alveolar FOAMY exudates
Pulmonary Fungal Infections
- Histoplasmosis
o Soil, bird/bat droppings
o Granulomatous inflammation, small black budding yeast
- Coccidiodomycosis
o Southwest
o Necrotizing granulomatous inflammation
- Cryptococcosis - india ink stain
o Soil, PIGEON poop
o Mucin positive
- North american blastomycosis
o mid west river valleys
o pus forming (suppurative)/granulomatous
o BROAD based budding
- Aspergillosis
o Allergic bronchopulmonary aspergillosis- immunologic
o Aspergilloma- colonizes pulmonary cavity- fungus ball
o Invasive aspergillosis- opportunistic infection
Vascular invasion, thrombus + infarct
Can see hyphae and fruiting bodies
Tuburculosis
- Gohn complex: peripheral granuloma, involvement w/ mediastinal lymph node
Stuff that forms Granulomas
Necrotizing
- TB
- Coccidiomycosis
Non-Necrotizing
Lung Cancer
Men, 60-70 y/o
Central Tumors
- small cell carcinoma
- squamous cell carcinoma
- branchial carcinoids
Peripheral Tumor
- adenocarcinoma
- hamartoma
Malignant
Epithelial Tumors
- squamous cell carcinoma
o smoking males, central lung- keratin pearls
o hemotypsis, symp due to obstruction
o superior vena cava syndrome- compression, dilation of upper body veins
o pancoast syndrome- shoulder pain- ulnar distribution: b/c tumor at apex compresses parts of brachial plexis
o Horner syndrome- b/c pancoast tumor that involves cervical symp plexus- ptosis, miosis, anhydrosis, endopthalmosis
o Massive hemorrhage, dilated bronchi mucopurulent secretions,
o 5 years, 15%
- adenocarcinoma
o peripheral, assoc with scars
o 5 year 15-20%
o Types
Acinar adenocarcinoma
• Gland arrangement, mucous secretions
Broncho-alveolar carcinoma
• Male female 1:1, 5 year 42%, multicentric/diffuse forms worse
• Neoplastic cells line "normal" alveolar architecture
• Types
o Solitary mass
o Multiple nodules- resembles metastatic cancer
o Multicentric diffuse infiltrate- resembles interstitial disease
Solid carcinoma w/ mucous cell formation
• Undifferentiated, anaplastic
Papillary adenocarcinoma
• Papillary structures with central fibrovascular core
Neuroendocrine Carcinomas (small and large cell carcinomas): acts like neuroendocrine system
Small cell carcinoma
o Males, smoking
o Worst prognosis 5 yr 4%, already metastatic by time of diagnosis
o Best response to cancer- important to ID as small cell for TX
o Central
o Types
Oat Cell
Intermediate
• Similar clinically
Combined- oat cell + any other type of tumor (squamous or adenoma)
• Perform surgery to remove
- Large cell carcinoma
o Poorly differentiated- no observable org via light microscopy
Electron microcsopy shows some organization
o cells with lots of cytoplasm (+ lymphocytes…not oat cells)
o Treat with SURGERY NOT CHEMO
Bronchial Carcinoids
- M=F, 45 y/o
- Central, peripheral, atypical
- Central
o GOOD PROGNOSIS- 5-10 y 50-95%!
o Maj metast to lymph, minor to liver
o YELLOWISH color
o Mass invading lumen of larger bronchi (more central)
o Invade bronchial wall into lung tissue
o Uniform cells, strippled chromatin, positive stain for chromogranin
o Can UNUSUALLY cause carcinoid syndrome (via seretonin secretion- skin flush, broncho const, cyanosis, R heart prob, hypotension,edema)
Metastatic Tumors
- lung 2nd most freq after lymph node
- Types
o Multiple- usu late stage cancers
o Lymphangitic- usu from adenocarcinoma
o Solitary- must distinguish from primary tumor
- usu from stomach, breast, colon, uterus, pancreas
Malignant Mesothelioma
- males, 40-70 y/o
- increasing in freq
- asbestos exposure (20-40 year lag)
- PLEURAL EFFUSION
- Pleural tumor encasing the lung- can extend to diaphragm
- Biphasic: epithelial/spindle
Benign
Hamartoma
- Peripheral, well defined
- hamartoma means like tumor, but due to faulty development
o microscopically can reproduce any component of bronchial tissue- cartilage, muscle, fat, cleft like spaces
Putting it all together….
Small cell carcinoma: major one for chemo
All other tumors- surgery is treatment of choice!!
Overall cancer survival rate: 5 years, 8-10 %
In order of better to worse
- squamous, adeno, small, large
Squamous cell, adeno= better prog
Small/Large cell= bad prog
Metastasis: most likely to least likely: lymph nodes, liver, adrenal, bone, brain
Paraneoplastic syndromes
Squamous cell carcinoma: hypercalcemia- PTH
Small cell carcinoma: cushing's (ACTH), inapprop ADH, carcinoid, gyneocmastia, acromegaly
Squamous cell and adenocarcinoma ( prob most frequent and increasing!)are most frequent lung tumors
- small cell and large cell also considered frequent
Drugs with Lung Toxicity:
Bleomycin
Busulfan
Amiodarone
Cyclophosphamide
Methotrexate and methysergide
Nitrosourea and nitrofurantoin
HY GI and Liver Path
As the Step 1 exam approaches for many of you, I give you all the credit. Did you know, you are one of 2% of the population that wants to go to medical school! Not only that, you did it! You have learned more in two years than an undergrad learns in 4!
Testing Strategy: Thinking globally/big picture, integrating material, making assertions, problem solving and reading comprehension will make these numbers take flight!
30% of the Test is Knowledge/recall. If you are working daily to put information in and paid attention in the 1st two years, you should be able to get 90% of this part of the exam. = ~27%
70% of THE test is problem solving/interpretation/integration of information. If you can just get to guessing ~ 50%, = ~ 35% of the this portion correct. That puts you at 62% of all your questions correct. That is the national mean for Step 1!
GI
Integrated Info
Men more likely to have
- Barrett esophagus
- Esophageal cancer ( Iran, china)
- Pyloric stenosis (newborns)
- Peptic ulcers
- Hirschprung's disease
Causes of hematemesis
- lacerations
- varicosities
- acute gastritis
- peptic ulcer
- Zollinger-Ellinson syndrome (lots of peptic ulcers)
Malignant Tumors with Bad Prognosis: Esophageal and Gastric carcinoma ( all forms EXCEPT flat intramucosal)
T-cell lymphoma- Celiac Disease (intestines)
B-cell MALToma- H.Pylori (stomach)
Esophagus
Plummer-Vinson syndrome: iron deficiency anemia, dysphagia, esophageal web, and atrophic glossitis.
- esophageal web- mucosal folds- narrowing of lumen
- ring
Boerhaave syndrome: spontaneous rupture of the lower esophagus, a variant of Mallory-Weiss syndrome.
Stomach
H. Pylori:
- chronic atrophic gastritis Type B
- peptic ulcers
- adenocarcinoma of the stomach
- B-cell lymphoma of the stomach (in MALT tissue)
Counter-intuitive
- Shock, hypotension, and ischemia can be a cause of acutge erosive gastritis
Zollinger-Ellison syndrome:
Gastrin secreting tumor (gastrinoma) likely to arise in the gastrinoma triangle (pyloric area, duodenum, head of pancreas). The bigtime gastrin secretion causes lots of HCL secretion which leads to peptic ulceration
- Clinical Clue: presence of peptic ulcers in abnormal places ( small intestine, Meckel's diverticulum..aka places other than the duodenum) because there is sooo much acid secretion, it can not be effectively neutralized
- Also will see malabsorption symptoms because the excessive acid will deactivate pancreatic enzymes
Gastrinomas- can be in duodenum, pancreas and cause multiple peptic ulcers in stomach
Krukenberg Tumor: gastric diffuse carcinoma (signet ring micro form) that metastasizes to the OVARIES
GIST tumor: Gastrointestinal stromal tumor- probably originate stromal stem cells that are precursors of smooth muscle cells- classified as GIST and not a leiomyosarcoma if the cells retain the phenotype of undifferentiated stromal cells, most stain for c-KIT; histology shows spindle and epitheloid types, arise from muscularis propria (smooth muscle), can occur in stomach, or small/large intestines
Intestines
Omphalocele- congenital anomaly umbilical hernia
If GI bleeding: check for
- peptic ulcers (bleeding most common complication)
- gastritis
- hemorrhoids
If all these turn out to be negative, consider ANGIODYSPLASIA
ANGIODYSPLASIA
- older people
- tortuous dilatation of mucosal and submucosal blood vessels, prone to rupture
- maybe part of
o hereditary hemorrhagic teleangectasia
o CREST syndrome
- cecum/right colon
Celiac Disease
- Ab to gliadin (and glutaminases)= antiendomysial antibodies
- HLA-DQ2
- Flattening of villi
- Allergy to gluten, respond well to gluten free diet
- Predisposition to T-cell carcinoma
Non-neoplastic polyp
- hyperplasia
- hamartomatous
o Juvenile
o Peutz-Jeghers polyps- irregularly shaped glands surrounded by smooth muscles- multiple hamartomatous polyps scattered about
- lymphoid
- inflammatory pseudopolyps from UC
Pre-disposition to Cancer of Large Intestine
- Familial adenomatous polyposis- multiple polyps- loss of APC
- Familial NON-POLYPOSIS carcinoma (LYNCH syndrome)-
Cyclophosphamide: treats UIP and Wegener's Granulomatosis
LIVER
HLA linkage: Hemochromatosis
Central lobular congestion- hepatic venous HTN leading to the right ventricle
Limiting plate- connective tissue found around portal tract (hepatic vein, portal vein, bile duct)
Interface hepatitis- inflammation crosses the limiting plate and infects the hepatocytes around it (aka-piecemeal necrosis)
Interstitial cell of Ito- stores Vitamin A
MAJORITY of blood flow INTO liver is through portal vein
- MINORITY is via hepatic artery
Blood flow through hepatic lobule (periphery-central) is OPPOSITE of bile flow (central-periphery)
- both bile stagnation AND blood outflow stagnation will be evident in CENTRAL lobe
The first part of the billiary system is located in the central lobe in the intercellular billiary canaliculi
Gynecomasty from liver failure is a result of failure to detoxify hormones in male
ALT- alanine aminotransferase.
AST- aspartate aminotransferase.
Hepatitis A- directly hepatotoxic
HepB- indirectly hepatotoxic via induction of T-cell immune response- makes granulomas- ground glass appearance
Voluntary intoxication with Tylenol- common cause of emergency liver transplantation
Liver disease skin manifestations:
Spider Nevi
Palmar erythema
telangiectasis
a lesion formed by a dilated capillary or terminal artery, most commonly on the skin., can be a sign of liver disease- SPIDER NEVI- telangiectatic arteriole in skin with radiating capillary branches can be seen in liver disease
Spleenomegaly is also a manifestation of liver disease (remember that liver helps with old RBC metabolism)
- is often accompanied by thrombocytopenia- (decreased platelets) because if spleen is enlarged, the platelets will get caught in spleen (sequestration) and can't go into blood stream
Cholestasis= OBSTRUCTIVE jaundice
Unconjugated bilirubin does NOT show up in the urine (i.e.- hemolytic jaundice or any disorder with accumulation of unconjugated bilirubin)
Bile formation: (spleen) heme--biliverdin--albumin-unconj. Bilrubin--(liver) conjugated bilirubin (with glucouronides via uridine diphosphate-glucoronosyl transferase UGT1A1)---bile---(ampulla of vater)---intestines (metab to urobilinogen---feces (and some in urine)--enterohepatic recirculation as urobilogen
- unconjugated bilirubin (i.e. prehepatic is not soluable, so thus will NOT show up in urine if have pre-hepatic jaundice)
- in obstructive jaundice (cholestasis)- bilirubin is conjugated, so WILL see in urine
Alkaline phsophatase: in liver cell membrane lining intercellular canaliculi, if these levels are increased means OBSTRUCTIVE JAUNDICE Measure obst
Hereditary Hyperbilirubinemias:
Unconjugated:
Gilbert Syndrome: hereditary syndrome, most common form of hereditary jaundice, mild jaundice- unrelated to other symptoms- episodic jaundice (fluctuating hyperbilirubinemia) brought about by stress, exercize, fasting..genetic mutation in UGT1, reduced activity in UGT…no treatment, does not damage liver
-
Crigler-Najjar syndrome- hereditary jaundice, deficiency in UGT- can not conjugate bilirubin
- normal looking liver, really elevated levels of unconj bilirubin
- type I- enzyme absent- bad, type II- reduced enzyme activity- not as bad
Conjugated
Dubin-Johnson syndrome: impaired biliary excretion of bilirubin glucouronides due to mutation in canalicular multidrug resistance protein 2 (MRP2)- responsible for transport of bilirubin glucuronides and related organic acids into the bile
- liver is darkly pigmented- due to granules of epinephrine metabolites (not bilirubin), hepatocytes look otherwise normal
Rotor Syndrome: decreased hepatic uptake and excretion, liver looks normal, patients exhibit jaundice, but otherwise look normal
Alpha-1 antitrypsin defiency
Alpha-1 antitrypsin defiency: can cause conjugated obstructive jaundice, AND liver cirrhosis, and increases the risk of hepatocellular carcinoma
- most common form of neonatal hepatitis
Cholangiocarcinoma: malignancy of billiary tree, see tubular glandular structures surrounded by sclerotic stroma, gross- multiple lesions, maybe looks like metastasis, BUT the lesions are not indurated in the middle
Risk factors:
- primary sclerssinc cholangitis
- Congenital fibropolycystic diseases
- Most in West are spontaneous
- Orient: infection with opisthorchis sinensis (liver fluke)
Oral contraceptives
- cholestasis
- liver thrombosis (drug induced vascular changes in liver)
- liver cell adenoma (benign)
Kayser-Fleisher ring- present on cornea (limbus) in Wilson Disease
Alcoholic liver disease- increased blood ceruloplasmin
Wilson disease- DECREASED blood ceruloplasmin (ceruloplasmin is a copper transport protein)
Antibodies
- Antinuclear (ANA), Anti smooth muscle (ASM)---------Autoimmune hepatitis
- Anti-mitochondrial-------primary billiary cirrhosis
- P-ANCA------primary sclerosing cholangitis
Women:
- Young- auto-immune hepatitis
- Older-premenapausal- primary billiary cirrhosis
Most common causes of fatty liver
- obesity
- alcoholism
- diabetes
Spleenomegaly-----a symptom of liver cirrhosis--harder to pump blood into a cirrhotic liver (same mentality as portal HTN)
Cirrhosis----spleenomegally----asoc with thrombocytopenia---low platelet count
Micro for Step 1 - quick hitters
57 quick hitting "to know" for the USMLE Step 1. There are some details here that will enable you to maximize your exam.
Remember! This is a thinking exam. They want you to understand the "Big Picture", then be able to relate details over a spectrum of presentations.
One: Read the stem
Two: Predict what they are asking and what an answer may entail.
Three: Look for clues within the vignette.
Four: Eliminate choices
Five: Answer
Six: Ask yourself. Does this answer their question?
1. Mycoplasmas lack peptidoglycan - are "cell wall-less" and live in association with eukaryotic cells
2. UDP is attached to the precursor but does NOT end up in peptidoglycan cell wall
3. Acid-fast and Gram negative both LACK sterols in their memb.'s, and both have 2 memb's.
4. Spirochetes and Gram neg. have an outer memb. containing porins- are needed to transport hydrophilic molec.'s
5. The end product of sporulation is a spore which is resistant to heat, detergents, dryness and DNA damaging radiation
6. Definition of species is arbitrary - b/c they reproduce asexually
7. Group Translocation: sugar uptake by bacteria where sugar is modified by phosphorylation - the phosphate in PEP ends up on the sugar. THE ONLY transport process where the substrate is modified during uptake.
8. Triclosan reduces the # of bacteria but does not sterilize
9. Quinolone - inhibits DNA gyrase, therefore, inhibiting DNA synthesis
10. Vancomycin - inhibits cell wall synthesis causing cell lysis WITHOUT attaching to PBP's. Vanco binds to the D-ala-D-ala of peptide side chain.
11. Gram pos.' do NOT use permeability for B-lactam resistance, b/c the PBP's (targets) are already outside the cell
12. Macrolide - bacteriostatic - reversibly blocks protein synthesis (the 50S)
13. Type III derived from flagella. Type IV derived from pili.
14. Sulfonamides - work by inhibiting bacterial folic acid synthesis
15. There is only a single RNA polymerase in bacteria
16. mRNAs are polycistronic
17. Transcription of genes for anabolic pathways can be regulated by BOTH positive and negative regulation
18. Transcription of most bacterial genes is controlled at the level of initiation
19. In the trp operon of E. coli - the translation of the upstream ORF controls formation of the attenuator, but the attenuator does NOT control translation
1. The trp attenuator system is a sensor of level of charged trp tRNA, but does not regulate the level of trp tRNA
2. attenuator system regulates transcription of the trp operon by premature termination of transcriptional elongation.
3. attenuator is a single-stem loop - tRNA is a cloverleaf structure.
20. DNA rep. in E. coli - bidirectional starting at oriC. dnaA binds initially to 9mer causing local denaturation, dnaC helps load dnaB helicase onto the origin
21. DNA polymerase III replicates both leading and lagging strands of DNA in E. coli
22. Competence factors are utilized in transformation in Gram POSITIVE bacteria, not gram negative. (pn-"competence is a positive thing"…)
23. Antibiotic treatment does NOT cause mutations
24. F+ cell's F pilus attaches to F- cell causing localized fusion, F plasmid DNA is nicked, allowing transfer of pre-existing strand of F plasmid DNA but not chromosomal DNA to recipient, converting it to an F+ cell.
25. Specialized Transduction - results in 2 copies of any bacterial genes in recipient cell. Uses a phage integrase to place entire transducing phage genome into the chromosome at an att site. Therefore, have one copy of some genes at both normal location in chromosome and at att site.
26. No gain in copy number of incoming gene - Transformation, Conjugation b/w Hfr and F- cell, & generalized transduction. These use homologous recombination.
27. IS elements on F plasmid allow it to become integrated into the host chromosome.
1. OriT is origin of transfer during conjugation
2. tra genes encode apparatus allowing transfer of DNA
3. OriV used for vegetative replication of plasmid
4. IS elements are small transposons homologous to IS elements on the chromosome.
5. Integration is by homologous recombination
28. Antibiotic resistance genes are usually found w/in transposons; transposons can transpose w/in a cell, but not b/w cells. Abx resistance genes are usually transferred b/w cells on plasmids by conjugation.
29. Antibiotic resistance acquired by MUTATION usually involves modification of the target of the antibiotic
30. Antibiotic resistance conferred by plasmid-encoded genes usually involves modification of the antibiotic itself.
31. IS elements are small transposons that encode only a transposase
32. Composite transposons have IS or IS-like elements at ends, NOT integrons
33. Tn3 type transposons encode their own transposase
34. TnA type transposons encode both a transposase and an Abx resistance gene
35. Integrons - build up arrays of Abx resistance genes on plasmids
- can provide promoters for Abx resistance genes
36. Composite transposons, Tn3 type transposons, integrons, and IS elements can all be found on R plasmids
37. Iterons are small repeated DNA sequences that occur at the OriV of some plasmids
38. Operons are the transcriptional units of bacteria
39. Food-borne cholera most commonly caused by under-cooked shellfish from Vibrio-infested waters
a. Note: If you are in restaurant where the water is not safe, drink alcohol w/ no ice.
40. V cholerae incubation range- 12 hrs. - 3 days.
41. Liver and Immune dysfunction predispose to V. vulnificus infection, often from Gulf Coast oysters. Aggressive in infection of skin and soft tissues
42. Cholera cause moderate fever, NOT high fever.
43. Most common commensal organisms in anterior urethra are lactobacilli, streptococci, and coagulase-negative staphylococci.
a. Lactobacilli colonize the vagina at birth
b. " are common in the stomach since they are acid-tolerant
44. Siderophores solubilize and sequester Fe3+
a. Most pathogens use iron:
i. as essential cofactor in e'n transport
ii. in RNA synthesis
iii. for resistance to ROS
45. Cholera toxin is an A-B toxin
a. A = active
b. B = binding
46. In Gram staining, if iodine mordant is not used effectively, Gram+ cells will take up safranin and appear red (like Gm-)
47. PCR reaction - DNA fragments are extended in a 5'-->3' direction.
48. Salmonella and Shigella are both lactose-neg., but Salmonella is motile while Shigella is non-motile
49. ETEC LT-1 is an A-B toxin structurally and functionally similar to cholera toxin: it binds to same receptor, has ADP-ribosylating activity which leads to increased cAMP levels. Fluid loss manifests as watery diarrhea.
50. Yersinia enterocolitica affects the terminal ileum - can mimic acute appendicitis if mesenteric lymph nodes are involved (pseudoappendicitis).
51. Shigella dysenteriae causes dysentery by invasion and replication in enterocytes lining colonic mucosa, cell-to-cell spread of bacteria, and by action of Shiga toxin
52. Campylobacter jejuni is the most common agent of gastroenteritis in U.S. - more cases than from Salmonella and Shigella combined.
53. Salmonella typhi and Salmonella paratyphi are strict HUMAN pathogens, no animal reservoir.
a. Maintained by human colonization, mainly of the gallbladder, sometimes w/o symptoms.
54. Salmonella colerasuis and Salmonella typhimurium have animal reservoirs, but can cause severe disease in humans
55. H pylori mediated damage to gastric mucosa is primarily caused by immune response- secretion of inflammatory cytokines such as- . . . ultimately leading to gastric epithelial cell death.
a. IL-8 - recruitment of neutrophils
b. PAF - stimulates gastric acid secretion
c. NOS - mediates tissue damage
56. EPEC are the ONLY group of E. coli expressing a Type III Secretion System (TTSS).
a. inject numerous effector molecules into intestinal epithelial cells by TTSS.
b. leads to close attachment of bacteria to epithelial cells and effacement of microvilli.
57. EHEC is associated w/hemolytic uremic syndrome (HUS).
a. HUS is associated with Shiga toxin (pref. Stx-2) expressed by EHEC, which destroys glomerular endothelial cells, leading to renal failure.
b. Note: Shigella dysenteriae also exrpresses Shiga toxin similar to Stx-1 of EHEC and can cause renal failure, though not as common.
Great Pharmacology review
If you would like to really rock the Pharmacology portion of the boards. Carefully go through this ppt and you will begin to understand the depths of knowledge you need to know.
Answer the questions in the middle. If you don't know them, have your handy Pharmacology reference book nearby. I recommend Rapid Review: Pharmacology
I can't wait to see how well you do!
Pharmacology Review
These are a few of the pearls gleaned from Thomas Pazdernik, PhD of pharmacology, author of a fantastic book:
Pazdernik
Once you have identified where the drug belongs, you need to ask yourself, “what is the basic mechanism of the drugs within that class?” Usually that comes to you pretty easily. A lot of times, when you can put it in the right class you will know the mech. Then, don’t memorize all the pharmacokinetics, but memorize the UNIQUE pharmacokinetics. There are some drugs that can’t be given orally. Like Aminoglycosides. There are some drugs that rely primarily on renal mechanisms for elimination. So if you have renal dysfunction, you need to adjust the dose. There are other drugs that depend primarily on the liver.
We should know the difference between Neostigmine and Physostigmine. Neostigmine you would use if you wanted to treat Myasthenia Gravis. If you’re going to treat Atropine OD, then you need to use Physostigmine. Physostigmine crosses the Blood Brain Barrier.
What’s hit very hard on the boards is side effect profile. And many of the side effects you can figure out because they’re kind of an overextension of the pharmacological effect. So you should be understand, if you understand autonomic physiology, some of the side effects of some of the autonomic agents we’ve studied.
A lot of drugs have a signature side effect. It’s a side effect that’s kinda unique to that drug. This is particularly relevant in the anti-cancer drugs. Those are hit hard on board exams. You should know for example that Cyclophosphamide causes bladder cystitis. That Vincristine causes neurotoxicity. That Methotrexate causes Hepatotoxicity. That Cisplatin cause Nephro and Neurotoxicity. Duanorubicin and Doxirubicin causes Cardiac Toxicity. Bleomycin and Lung Toxicity. This is what I mean by signature side effects. These side effects are often kinda the rate limiting effect of the drug when it’s used clinically.
Then you should also have a good idea of some of the common uses of drugs. You don’t need to know all of the indications for a drug, but you should know how to treat Asthma. Know how to treat Arrhythmia and be able divide them into their classes.
Now what you uses to study for the boards and for your final depends a little bit by how you studied as you went through the course. Probably most of you are not going to have enough time to go back through all of your notes. If you made summary sheets or charts, you should use those.
Board Review books can also be very helpful at this point in time. There as helpful as how well you learned the material the first time you went through it. If you didn’t learn the material as you went through the course, then First Aid for the Boards is not going to be very meaningful to you at all.
I think maybe one of the best sources for the boards and maybe be more than what you can handle for the final, is the rapid review book that we’ve just came out with. It’s the Pharmacology Rapid Review Book by Mosely. This book is meant to be somewhere between what’s in First Aid and what’s in Baby Katzung. The strength of this is the disk in the back that has 500 questions that you can take in a tutorial mode or in an exam mode. If you take it in a Tutorial mode you can pull up the questions on Antibiotics. It will give you feedback as to whether it’s right or wrong. IF you take it in the exam mode it will give you 1 hour to do 50 questions. You can either do that within a subject area or a whole area of pharmacology. 100 of those questions are in here as a paper/pencil format. You can take it as an exam and go back and look at it.
One program on the web that is very high yield is under the General Principles Section. There’s a program that’s called MATCHING QUIZ. It kinda lists the hallmarks of some of the older classical drugs that are used to describe certain phenomena. Like Tetracycline causes discoloration of teeth. That Phenobarbital induces cytochrome P450. Phenoxybenzamine forms a covalent bond with the receptor.
On the board exams you’ll see a higher emphases on old classical drugs and prototypic drugs. It won’t necessarily look like the clinics are going to look. The drugs usually are chosen to illustrate a principle and if you’ve learned that principle, then it probably will be quite obvious why that drug is the right answer. So I think the matching thing is helpful.
Look at the clinical vignette-type questions presented in this course. We try to use questions that are very much like those that are on the board. A lot of those questions, you need to know 2 or 3 things to get them right. Q-bank from Kaplan is also very useful in preparing for the boards as well.
Look at table and figures when you look through your review books. Compare and contrast drugs. Many have done well on rote memorization from notes, but the boards will not be like that. You shouldn’t memorize verbiage, but you should understand the principles involved. A lot of the board questions are written so that most of the foils sound pretty good. If you really understand the basic principle, the right answer should be pretty obvious. Some situation that they’ve put the subject in may make one answer superior to the others.
Here’s an example:
Amiodarone has now become the recommended drug by ACLS for life threatening ventricular arrhythmias, but if you have a little clinical vignette with someone with severe COPD… then you’d go back to Lidocaine. The key here is that you have to recognize that Amiodarone has lung toxicity and should certainly be avoided.
You should have a good understanding of Absorbtion, Distribution, Metabolism and Excretion.
Some of the formulas that you might be seeing on the final or that you might be seeing on the boards… These are the ones you should probably know.
Vd = Amt. injected
--- ----------------
Amt. injected at time zero
Vd = Amt. IV
------------
C0
Kel = 0.7
-----
t ½
Cl = Kel x Vd
X = Css x Vd
Css = input = F x D/T
------ -----------
output Cl
IF you can work with these equations, you should be able to do any of the questions that you’ll be faced with.
Other important items you should know for boards:
- The difference between a Zero order and First order reaction, and how you would graph that
- Understand Half-life, 50% of the drug after one half life, 75% after two, 87% after three, etc.
- There’s a fair amount of questions that deal with Signaling Pathways, maybe more coming of Biochemistry than from Pharmacology
- You should know the kind of drugs that affect Gene Expression, like steroids for example. There’s multiple drugs (both endocrine and autonomic) that affect cAMP pathway. The PI pathway. You should know N.O. and EDRF. Also the various ionotropic mechanisms.
- Dose-Response curves—you should know the basic terminology like what is an agonist, what is potency, what is affinity.
- Understand graphically the difference between a full agonist and a partial agonist. Also an inverse agonist.
- Understand the various way for graphing a competitive antagonist vs. a non-competitive antagonist. Understand the various ways you can plot this, like Lineweaver-Burke, etc.
- Know the examples and definitions of Pharmacokinetic Tolerance, Pharmacodynamic Tolerance, the phenomena of Tachyphylaxis particularly with indirecting amines depleting the store of norepinephrine, Desensitization—usually due to a relatively rapid inactivation of a process (Ion channels can get trapped in an open or closed state—for example the nicotinic receptor), Down regulation—agonists down regulate receptor numbers per unit of tissue
- You should know terms like Therapeutic Index, Margin of Safety,
- You should know substances that are teratogenic
- Fetal toxicity
- Clozapine - Agranulocytosis (type II)
- Serum Sickness - Type III
- Contact Sensitivity - type IV, like poison ivy
- You should know and understand the abnormal responses that are influenced by Genetics
- Inducers and Inhibitors of P450, know that Valproic Acid inhibits Cytochrome P450 (it’s the one that’s different from some of the other drugs used like Primidone, etc.)
- ST. JOHN’S WART induces Cytochrome P450
- Inhibitors—particularly Macrolide Antibiotics and Azole Antifungals!
Chemotherapy will be the hardest section. Spend some time with it.
Buzzwords for Chemotherapy
| Drug that blocks excretion of penicillin and therefore can increase it’s half life | probenecid |
| Type of penicillin that has a half-life of more than 2 weeks and is considered a DEPOT form of penicillin | Benzathine Penicillin G |
| Which generation(s) of cephalosporins can enter the CNS | 3rd and 4th |
| This cell wall synthesis inhibitor is inactivated by renal dipeptidase | Carbapenem (imipenem) |
| What is cilastatin used for | Cilastatin blocks the metabolism of imipenem by renal dipeptidase and can therefore increase it’s half-life |
| This cell wall synthesis inhibitor is associated with Red Man Syndrome | Vancomycin |
| Don’t give this protein synthesis inhibitor to children because it can concentrate in their teeth and growing bones | Tetracycline |
| This protein synthesis inhibitor is associated with Gray Baby Syndrome | Chloramphenicol – babys are poor glucoronidators L |
| This protein synthesis inhibitor is a potent inhibitor of CYP3A4 and went through FDA accelerated approval | Streptogramins |
| This protein synthesis inhibitor follows “Once daily dosing” | aminoglycosides |
| This folic acid inhibitor is also used in Ulcerative Colitis as a topical anti-inflammatory | Sulfasalazine |
| This DNA gyrase inhibitor has been associated with spontaneous rupture of Achilles tendon in animal rats | Fluoroquinolones |
| This urinary tract antiseptic works best in acidic urine | Nitrofurantoin |
| Name three systemic antibiotics that are used to treat UTI because they are efficiently cleared in the urine | Penicillin Aminoglycoside Sulfas |
| This 1st line antimycobacterial drug is associated with resistance from deleting katG gene | Isoniazid (kat G gene is the gene that encodes a catalase that activates Isoniazid) |
| This 1st line antimycobacterial drug inhibits synthesis of arbinogalactan and is associated with visual disturbances(optic neuritis, low acuity, red-green problems) as it’s adverse effect | Ethambutol |
| This 1st line antimycobacterial drug is the only drug know to target RNA synthesis | Rifampin |
| This anti-parasitic drug is known to concentrate in the liver, spleen, and kidneys and is slowly released from those sites | Pentamidine |
| This alkylating agent is part of the MOPP regimen and is administered in arterial supply to the tumor | Mechlorethamine |
| This alkylating agent is associated with hemorrhagic cystitis which can be prevented with administration of mesna and adequate hydration | Cyclophosphamide |
| This alkylating agent is leukemogenic, teratogenic and is part of the MOPP regimen | Procarbazine |
| This anti-metabolite can be given in a high dose followed by “rescue with folinic acid (citrovorin, leucovorin)” | Methotrexate |
| Resistance to this group of anti-metabolite drugs is associated with a decrease in hprt activity | Purine Analogs: 6-Mercaptopurine 6-Thioguanine |
| These plant alkaloids are known as “spindle poisons” and stabilize microtubules so much so that they can’t be pulled apart | Taxol/Taxotere (used predominantly in breast and ovarian cancer) |
| This anti-tumor antibiotic is associated with cardiotoxicity | Daunorubicin/Doxorubicin |
| This anti-tumor antibiotic is associated with pulmonary fibrosis | Bleomycin |
| This anti-tumor antibiotic has mechanism of action that is favored by hypoxia | Mitomycin – this is also the most toxic of all anti-tumor antibiotics |
| This anti-tumor antibiotic can be administered by bladder instillation | Mitomycin |
| GnRH antagonists are used to treat this type of cancer | Leuprolide is used to treat Prostrate cancer |
| Name the aromatase inhibitor that blocks the conversion of androgen to estrogen and is used in breast cancer unresponsive to tamoxifen | Triazole |
| Which tyrosine kinase inhibitor inhibits bcr-abl and is a great drug for CML | Gleevec |
| Estrogens are used to treat what type of cancer | Prostrate |
| Androgens are used to treat what type of cancer | Breast |
CNS, and Autocoids, and Toxicity, should come back pretty easily.