Note: the following material is for personal use only see below for

Restrictive pericarditis

Definition: pericardial pressure ≥ RA pressure / equalization of pressure in the four chambers during diastole / pericardium can accommodate from 200 to 2000 mL depending on acuteness of situation

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  Beck’s Triad: hypotension, elevated JVP, small quiet heart
  

Note: preload is badly needed  preload reducers are contraindicated (diuretics, nitrates, etc.)

Chagas disease (Trypanosoma cruzi) (20% develop CHF)

Idiopathic giant cell myocarditis (affects healthy, young people)

Allergic myocarditis (eosinophilia)

Other autoimmune: polymyositis, scleroderma, SLE

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  Arrhythmias: probably good idea to push low dose b-block or stronger as needed / be careful with digoxin (only use low doses, may worsen inflammation)
  
  • 
    consider transfer to hospital equipped with LV assist devices in case of rapid heart failure
    
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  bed rest (exercise shown to increase viral replication and worsen outcomes; rest for at least a week? 3^rd leading cause of sudden cardiac death in athletes), eliminate unnecessary meds (esp. with eosinophilia)
  
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  avoid anticoagulation (as much as can in case of hemorrhage into pericardium)
  
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  treat underlying cause / immunosuppression for autoimmune diseases (including giant cell myocarditis) but not helpful for infectious or post-infectious / INF-a currently under investigation for viral myocarditis
  

Occluded subclavian artery (usually on the left) leads to collateral perfusion of shoulder joint from vertebral artery / symptoms are intermittent arm claudication and syncope and/or ataxia, confusion, vertigo, dysarthria from exercise-induced decreased vertebrobasilar perfusion leading to Treatment: bypass

May impair blood flow through subclavian artery / Treatment is resection of rib

Heart Transplant
survival 76% at 3 yrs / transplant half-life ~9.3 yrs / chronic cardiac transplant rejection manifests as CAD with characteristic long, diffuse, concentric stenosis / only definitive therapy is retransplant

Oncology
General: markers, associations, tumor biology, patterns of spread, BMT, neutropenic fever

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  Huge list of chemotherapy protocols
  

CA-15-3

CA-19-9 pancreas

Bombesin neuroblastoma, small cell carcinoma, gastric, pancreas

S-100 melanoma, neural tumors

A-FP HCC, yolk sac tumor (NSGCT) / also B-hCG, a1-AT

B-hCG choriocarcinoma

PSA prostate
Tumor Associations
Visceral malignancy [dermis]

acanthosis nigricans, dermatomyositis, flushing, acquired icthyosis, thrombophlebitis migrans
Intrathoracic tumors (lung cancer)

clubbing of fingers

Cowden’s, breast, intestinal, TS, skin, cardiac

minimal change disease, HSP, GCA, granulomatous angiitis of CNS

HBV, HCV – HCC

PAN – hairy cell leukemia

Wegener’s – Hodgkin’s disease
Specific Syndromes
Tuberous sclerosis

astrocytoma, cardiac rhabdomyoma (facial angiofibroma, SZ, retardation)

SCC of esophagus (atrophic glossitis, upper esophageal webs, iron deficiency anemia, women)

Sebaceous tumors associated with visceral neoplasms

AD / Colon CA / Increased risk for breast/thyroid CA
Cowden Disease (Multiple Hamartoma Syndrome) [pic][pic]

AD / cobblestoning of oral mucosa (trichilemmomas) / breast, thyroid, uterine, brain tumors / also have multiple small hamartomatous polyps in GI tract (not considered premalignant)

use plasmin, type IV collagenase, etc.

cleavage products PDGF, V-sis, EGF, CSF-1

membrane receptors c-erb-B2 (breast, ovarian, gastric), c-neu, c-fms

cytoplasmic receptors c-src, v-src / tyrosine kinase P-vinculin

G-proteins h-ras, k-ras, n-ras

nuclear proteins c-jun, c-fos, c-myb (transcription factors), c-myc (many cancers), l-myc (SCC lung), bcl-2 (lymphomas), ret (MEN)
BM type IV collagen, laminin / bind to and secrete laminin

ECM type I collagen, fibronectin / bind to fibronectin

platelet covered tumor thrombi / NK cells may destroy tumor cells
activation

point mutation (ras) / translocation (c-myc)

gene amplification (n-myc - neuroblastoma, c-neu - breast cancer)
Tumor Suppressors
Rb retinoblastoma

p53 colon, liver, breast

Wt Wilm’s tumor (children)

VHL renal cell carcinoma

APC colon

BRCA-2 breast

BRCA-1 breast, ovarian

NF-1 neurofibroma

NF-2 neurofibroma type II (acoustic)

DCC colon, stomach

DPC pancreatic
Carcinogens

alkylating agents

polycyclic aromatic hydrocarbons (tobacco combustion, smoked meats)

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  Tobacco increases risk of lung, bladder, esophageal and head and neck cancer (studies have shown passive cigarette smoke imparts 25% increase risks of all associated mortality including cancer, heart, respiratory illness)
  

natural (aspergillus flavus in grains, peanuts)

nitrosamines, amides (GI cancer)

asbestos, vinyl chloride, arsenic, insecticides

UV UVB (xeroderma pigmentosum)

ionizing leukemia, thyroid, breast, lung, salivary (NOT skin, bone, GI) / ataxia telangiectasia

DNA repair XP, AT, Fanconi’s anemia, Bloom’s syndrome

HPV, EBV (nasopharyngeal, Burkitt’s), HBV (HCC), HTLV-1 (RNA gives T-cell leukemia), HHV-8 (Kaposi’s sarcoma)

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  Elevated LDH or B2-microglobulin levels in lymphomas increase likelihood of CNS mets
  

thyroid, prostate, breast, melanoma, lung / (multiple myeloma, leukemias, etc.)

bronchogenic carcinoma > breast > melanoma > renal cell carcinoma > colon, lymphoma

lung, pancreas, stomach, colon > prostate, ovary >>> breast, brain, kidney, lymphoma

Trousseau’s syndrome usu. pancreatic or other GI

Hepatic or portal vein thrombosis myeloproliferative disorders (PNH, PRV, essential

thrombocythemia)

Tumors of fibrous tissue
Fibroma most common in ovaries

Fibrosarcoma lower extremities (45%) > upper extremities (15%) > trunk > head,

neck

benign fibrous histiocytoma cutis or subcutis / extremities

storiform/pleomorphic (worse) > myxoid, inflammatory / mets mostly to lungs (hematogenously)

Treatment: surgical +/- chemotherapy/radiation adjuvant or palliative
Fibromatoses

relapse but do not metastasize / palmer pattern causes Depuytren’s contracture (50% bilateral) / penile fibromatosis causes Peyronie’s disease (Bill Clinton)

can compress vasculature mimicking various vasculitides or vaso-occlusive diseases

leiomyosarcoma larger, softer, hemorrhage, necrosis, metastases

granular cell tumor benign

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  Usu. > 60 yrs / median survival 4-11 months (best hope is for cancer to be a nearby met from treatable solitary tumor)
  
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  CUPS syndrome (biopsy proven malignancy with path not c/w primary tumor + unrevealing workup)
  
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  adenocarcinoma > poorly differentiated carcinoma
  
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  pancreas, breast, colon, prostate, lung
  
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  2% of all cancer diagnoses / 5% of newly diagnosed mets are unknown primary
  
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  work-up based on findings, consideration of patient’s life-expectancy (usually 6 months), and then consider whether certain tests will change management / abdominal CT, CXR, occult blood (why do colonoscopy or ERCP if no symptoms), PSA (very different treatment), aFP, B-HCG
  
  • 
    extragonadal germ cell syndrome: < 50 yrs, midline structures, parenchymal lymph nodes, lung, elevated aFP or B-HCG, rapid growth / cisplatin-based chemotherapy offers 20% chance of cure
    
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  PET scans may identify primary site but have not been shown to increase survival
  

can try NSAID’s (thought to reduce fever caused by many ?solid tumors) / often used as a diagnostic/therapeutic tool

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  Gompertzian kinetics suggests benefits of adjuvant chemotherapy to treat micromets
  
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  Combination chemotherapy for maximum cell kill, broader range of kill, slows emergence of resistance
  
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  Choose – some action as single agent / non-overlapping / optimal dose and schedule
  

Mediastinal irradiation: acute or chronic pericarditis (mean onset 9 months; can manifest years later), myocardial fibrosis, accelerated atherosclerosis

normal kidney can clear 20 L/day

GFR = (U_Cr x Ur vol) / (P_Cr x time)

Note: decreased flow in tubules allows back diffusion of urea (but not creatinine)

Afferent constriction (influx of extracellular Ca – affected by Ca channel blockers)

Efferent constriction (influx intracellular Ca – not affected by Ca channel blockers)
Normal protein loss:

Men – 15-20 mg/kg/day lean body mass – 50 +/- 2.3 x inches over/under 60

Women – 10-15 mg/kg/day lean body mass – 45.5 +/- inches over/under 60
Renal Studies
Renal Ultrasound

ARF: number, size, shape, hydronephrosis/hydroureter (10%-20% smaller by U/S than IVP), can sometimes detect renal stones, abdominal aneurysms, and renal vein thrombosis

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  Large kidneys: multiple myeloma, amyloidosis, early DM, HIV nephropathy, pyelonephritis
  

Can diagnose hydronephrosis, 1^st line (after KUB) for evaluation of renal stones, determine if cystic masses (benign or malignant)

Can provide information about kidney ultrastructure (size, shape, mass) and function (obstruction) / CT can do most of the same things

inject contrast during cystoscopy (only perform after intravenous urography) / used when urography does not visualize kidneys and collecting system and obstruction is suspected

Useful for evaluating renal allograft function

When cause of nephrotic syndrome is sought

acute inflammatory lesion requiring cytotoxic therapy

Note: wire-loop lesions or sub-endothelial deposits are not disease specific / huge sub-endothelial deposit may resemble a thrombus
Cystoscopy

For urethral obstruction (always) and ureteral obstruction (sometimes)

Color

Glucose

Protein

Urine pH

Sediment

Cells [pic]

Bacteria

Casts RBC casts – glomerulonephritis [pic]

WBC casts – glomerulonephritis [pic]

Muddy brown casts – ATN

Hyaline casts [pic]

Fatty casts [pic]

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  average daily Cr production in men is 16 to 25 mg/kg (women 15 to 20 mg/kg) / 24 hr sample should have this amount of creatinine (otherwise it is an inadequate sample)
  

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  Interfere with tubular secretion
  

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  Interfere with lab measurement
  

GI bleeding

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  > 30 mg/24 hrs albumin excretion is considered abnormal (microalbuminuria)
  
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  > 300 mg/24 hrs is nephrotic range proteinuria
  
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  urine dipstick can detect if more than 500 mg/day / > 90% sensitivity/specificity but doesn’t account for variations in urine creatinine
  
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  spot albumin/creatinine ratio > 30 mg/g creatinine is considered microalbuminuria / > 95% sensitive, specific
  

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  Transient increased proteinuria (albuminuria): exercise, short-term hyperglycemia, urinary tract infections, marked hypertension, heart failure, and acute febrile illness
  
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  False positive: menstrual bleeding in women
  
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  Note: dietary protein intake does not cause microalbuminuria, but patients with diabetic nephropathy are advised to take low protein diet (0.6g/kg/d)
  

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  Proteinuria (normally prevented by large size, net negative charge)
  
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  Edema (from salt retention)
  
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  Hypoalbuminemia
  
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  Hyperlipidemia (decreased oncotic pressures triggers liver to produce lipoproteins)
  

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  Hypercoagulable state (↓ATIII, protein C/S)
  
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  Vitamin D deficiency (loss of Vitamin D binding protein)
  
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  Iron deficiency anemia (loss of transferring)
  
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  Hypogammaglobulinemia (increased susceptibility to bacterial infection)
  

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  Urinalysis: urine dipsticks (albumin only) and sulfosalicylic acid precipitation (albumin, paraproteins, immunoglobulins, and amyloid)
  
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  24-hour urine for protein (better for low urine output) / urine protein electrophoresis / serum lipids / lipiduria is suggested by oval fat bodies on microscopic study
  
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  Biopsy (if no obvious cause and significant proteinuria) / EM, IF, special stains (e.g., Congo red for amyloid)
  

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  Control blood pressure: this is the most important thing, more than ACE even, goal is to use MAP of 80-100? (too low is also bad)
  
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  ACE inhibitors or ARB’s (decrease proteinuria, reduce progression; also, low protein diet helps reduce amount and toxicity of proteinuria)
  
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  Diuretics (for overload): reasonable goal is 0.5 – 1 L/day (usually need Lasix (+) to achieve; go slowly; do not volume deplete; note: because HCTZ and Lasix are highly protein bound, there is reduced delivery to kidneys and large doses are often required to get same effect)
  
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  Control hyperlipidemia: dietary changes + statins / this is not optional, these patients must be on statins (note: lipoprotein-a elevations unresponsive to statins)
  
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  Note: calcium channel blockers worsen proteinuria by decreasing afferent > efferent thus raising intraglomerular pressure
  

Only happens when patient has been standing (so use nocturnal urine collection in patients who exercise vigorously) / remain constant at about 0.5-2.5 g/24 hr

Albumin, Tamm-Horsfall protein and B₂-microglobulin

drug-induced disease, chronic inflammatory disease (e.g., sarcoidosis), analgesic nephropathy

Treatment: remove offending agent / treat underlying disease
Renal Vein Thrombosis (RVT) (lots of proteinuria)

Causes:

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  Nephrotic syndrome
  
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  Renal cell carcinoma with renal vein invasion
  
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  Pregnancy or estrogen therapy
  
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  Volume depletion (especially in infants)
  
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  Extrinsic compression (lymph nodes, tumor, retroperitoneal fibrosis, aortic aneurysm)
  

Isolated Hematuria  stones, trauma, prostate > tumor (15%), Tb

Causes and microscopic findings:
Intrarenal

trauma, renal stones, GN, infection (pyelonephritis), neoplasia (RCC), vascular (renal thrombosis)

trauma (Foley), infection (urethritis, prostatitis, cystitis), ureteral stones, neoplasia (prostate, bladder)

Glomerulonephritis	Gross or microscopic hematuria, abnormal proteinuria, red blood cell casts / dysmorphic red cells on phase-contrast LM
Diffuse (SLE, vasculitis) Focal (IgA nephritis)	gross or microscopic hematuria without proteinuria, thin basement membrane / dysmorphic red cells
Vascular disease	Gross or microscopic hematuria without proteinuria isomorphic red cells
Tumors (hypernephroma)	Isomorphic red cells
Trauma, kidney stones, systemic coagulopathies	Isomorphic red cells

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  Dipstick (hemoglobinuria vs. myoglobinuria) / positive heme (orthotolidine test) and no RBC’s suggests pigmenturia / red urine without hemoglobin or RBC’s is rare (beeturia, porphyria)
  
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  Urine culture
  
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  IVP for renal masses, cysts, AVM, papillary necrosis, ureteral stricture or obstruction by calculus, bladder tumor, and ureteral deviation / other: angiography and nuclear scans (rarely used to delineate mass lesions)
  
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  MRI/CT (mass effects, surrounding structures)
  
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  Cystoscopy (when other tests non revealing)
  
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  Biopsy (sometimes needed)
  

GFR of 10-15% /Cr not always reliable marker for GFR / usually 0.5 to 1.0 mg/dl/day increase in Ser Cr, > 1 mg/dl/day suggests obstruction or rhabdo/tumor lysis syndrome

volume depletion, ↓ perfusion, renal artery obstruction

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  FeNa <1%, U_Na <20 mEq/L (this is the most useful of these in that if elevated, pre-renal is unlikely)
  

ATN: ischemia, toxins, pigments

Nephrotoxicity

Intrinsic: GN, TIN, vasculitis (HUS/TTP)

Systemic: atheroembolic syndrome, scleroderma, malignant HTN

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  ATN, TIN  FeNa >1%, U_Na >20 mEq/L (tubules broken, so can’t retain Na)
  
• 
  GN  FeNa <1% (unreliable), U_Na variable (kidneys try to retain Na)
  

Obstruction: tubular, pelvic, ureteropelvic, ureteral, bladder

Drugs: antihistamines, TCA

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  Early  FeNa <1%, U_Na <20 mEq/L (due to intense vasoconstriction)
  
• 
  Late  / FeNa >1%, U_Na >20 mEq/L
  

Rising BUN and serum creatinine (can be asymptomatic) / BUN reflects dietary intake, protein breakdown and resorption of GI or soft-tissue hemorrhage / creatinine reflects muscle breakdown (rhabdomyolysis, steroids, tetracycline), renal secretion (blocked by drugs like cimetidine and trimethoprim), chromogens (usually drugs) can cause measurement errors.

Anuria (< 100 ml/day) usually worse prognosis

Oliguria (< 400 ml/day) (most ARF patients)

Polyuria (> 800 ml/day) (25%-50%) (common with partial obstruction)

surgical, IV contrast, meds, allergies, chronic disease, FHx, signs of volume depletion, CHF

acute allergic interstitial nephritis: periorbital edema, eosinophilia, maculopapular rash, and wheezing

obstruction: suprapubic or flank mass, symptoms of bladder dysfunction
Uremic syndrome: nausea, lethargy, pruritis, pericarditis, uremic frost (skin), asterixis, uremic fetor (breath), platelet dysfunction
Note: uremic pruritis responds well to UVB radiation
Urinalysis

Only hyaline casts: pre-renal or post-renal

RBC: calculi, trauma, infection, or tumor

WBC: infection, immune-mediated inflammation, or allergic reaction

Eosinophiluria: 95% of acute allergic interstitial nephritis (Hansel’s stain tells E from PMN)

Pigmented casts and > tubular epithelial cells in 75% of ATN (casts without RBC’s  hemoglobinuria or myoglobinuria)

RBC casts: acute glomerulonephritis

Urine culture

Chemistries: FeNa < 1 suggests not ATN more than it actually proves pre-renal (exceptions: ARF from rhabdomyolysis and IV contrast are notably associated with FeNa < 1) / BUN/Cr > 20

Most useful: renal U/S >> AXR, cystoscopy

Less useful: isotopic flow scans, abdominal CT, biopsy
Course: azotemic, diuretic, recovery

Oliguric (50% mortality): more GI bleeds, sepsis, metabolic acidosis and CNS abnormalities

Nonoliguric: 26% mortality
Prognosis

60% mortality when surgery/trauma, 30% when medical illness, 10%-15% when pregnancy

Ischemic ATN has two times higher mortality over nephrotoxic ATN

Complete recovery in 90% if no complications

Correct: obstruction, nephrotoxic drugs, infections, electrolytes

Optimize intravascular volume and cardiac performance (can maintain output with Lasix)

Note: mannitol does not help, Lasix may increase urine output (but is more likely to decrease renal perfusion than help kidney recovery, it merely indicates less severe ARF)

Investigational: selective D1 agonists (renal dose dopamine is BS), Ca channel blockers (to increase renal perfusion), IGF-1 (may speed recovery of renal function)
Fluid/Electrolytes

I/O’s sensible losses (urine, stool, NG, other tubes) and insensible (400-500 ml/day)

sodium and potassium

Sodium bicarbonate if serum bicarbonate < 16 mEq/L

Oral phosphate-binding antacids (Al³⁺OH₃) if serum phosphate > 6.0 mg/dl

No Mg containing drugs

volume overload

hyperkalemia ( > 6.5 or EKG changes is an emergency)

hyponatremia, hyperphosphatemia, acidemia, hyperuricemia

hypocalcemia (decreased D-1,25, hyperphosphatemia, hypoalbuminemia)

hypercalcemia (rarely follows rhabdomyolysis)

bleeding (uremia/DIC), seizures (uremia)

chronic renal failure (10% show decreased renal function for months, pre-existing renal disease will likely progress to CRF)