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!