Hypercalcemia

physiology:

 

·        Adult body has 1 kg of Ca (99 % in bones as hydroxyapatite)

·        Circulating calcium in tight range of 2.25 -2.5 mmol /L

·        50-60 % protein bound (albumin), or complexed with phosphate/citrate

·        40-50 % free or ionized; proportion that is regulated and responsible for symptoms

·        so for every drop in albumin by 10, Calcium drops by .2 mmol /L

 

PTH à from parathyroid glands

·        glands sense [calcium] with calcium sensing receptor

·        low Ca increases secretion and vice versa

actions

·        Kidneys: increases Ca reabsorption + phosphate excretion / stimulates 1-alpha-hydroxylase so more 1, 25 Vit D

·        Bone: activates osteoclasts liberating calcium from skeleton

 

1, 25 Vitamin D: 

·        cholesterol in skin, light converts it to cholecalciferol ? or get from diet, liver converts it to 25- hidroxycholecalciferol, kidney converts it to 1,25-dihydroxycholecalciferol

actions

·        Gut: increases calcium / phosphate absorption

·        Bone: increases bone turnover as well

 

Calcitonin

·        parafollicular cells in thyroid gland secrete it/tries to lower calcium level

 

Signs + Symptoms (moans /bones /stones /psychic overtones)

·        related to degree or rise and absolute value

·        polyuria / polydipsia (due to nephrogenic DI)

·        GI discomfort: anorexia, constipation

·        mental status changes: apathy, fatigue, coma

·        pancreatitis, renal stones, band keratopathy (calcium deposits on cornea), ECG: shortened qt

 

W/U: Do PTH/lytes/extended lytes/cre/ maybe 24 hr urine Ca

 

a. PTH mediated (high / inappropriately normal)

b. non PTH mediated (if suppressed)

 

PTH mediated

·        Hyperparathyroidism (most common cause in outpts): primary when parathyroid out of whack due to adenoma or hyperplasia; secondary when CKD causes low calcium as vit D production impaired, PTH increases; tertiary when autonomous nodule develops in CKD

-        Generally get osteoporosis, in past presented with osteitis fibrosa cystica (skull demineralization/resorption of finger periosteum), kidney stones as more filtered calcium, can lead to nephrocalcinosis

-        Multiparathyroid adenomas generally seen in MEN 1 (pituitary, pancreas) or 2a (med. Thyroid, pheo)

·        FHH (familial hypocalciuric hypocalcemia): autosomal dominant deactivating mutation in Calcium sensing receptor in parathyroids and kidney

Dx with fractional excretion of calcium: (24 hr U Ca / serum Ca) / (24 hr U cre / serum cre)

24 hr U ca < 100 mg / FE_Ca < .01

·        Lithium : increases set point for PTH suppression by calcium

 

Non-PTH mediated

 

·        Malignancy (most common for inpatients), due to local osteolytic activity, PTHrP (humoral), calcitriol..

a.      Osteolytic tumors: myeloma, breast Ca, lymphoma

b.      PTHrP (PTH related peptide): protein produced by malignant cells, generally SCC of head + neck, AdenoCa of breast+ovary, RCC, myeloma. Cells produce small amounts of PTHrP so need a lot of tumor to be the cause.

c.      Increased calcitriol production: B cell lymphoma

 

·        Granulomatous disease (due to increased calcitriol production by autonomous production of 1alpha-hydroxylase): sarcoidosis, tuberculosis, leprosy, wegener’s (GPA)

·        Thyrotoxicosis, prolonged immobilization, paget’s disease: increased turnover

·        Vitamin D intoxication

·        Milk-alkali syndrome: when large amounts of calcium and consumed (> 4 g/day), get polyuria, leads to contraction alkalosis

·        Meds: Thiazides (increase Ca absorption)

 

Management

·        lytes/extended lytes/cre/ maybe 24 hr urine Ca/ calcidiol (25-vit D)/ calcitriol

·        w/u appropriate for underlying cause

·        IV fluids (dry secondary to polyuria)

·        Diuresis? Only if patient is euvolemic to hypervolemic

·        Bisphosphonates: Pamidronate (60-90 mg IV) or zoledronic acid 4 mg IV; calcium begins to decrease at 48-72 hrs; effect lasts for weeks

·        Calcitonin: 4 IU/kg sc q12h; acts quick; tachiphylaxis

·        Glucocorticoids: in Vit D mediated hypercalcemia like lymphoma and granulomatous disease; decrease intestinal absorption, and decrease activity of 1alpha hydroxylase

·        Gallium nitrate, plicamycin

·        Dialysis may be indicated in nothing works

·        Primary hyperparathyroidism:

Indications for surgery: symptoms!, age < 50, Creatinine Cl reduced by > 30 %, Ca > 2.75, high 24hr urine calcium, T score < -2.5

May localize with nuclear scan +- ultrasound; remove adenoma; remove 3.5 glands if hyperplasia (may be guided by intraop PTH levels)

Bisphosphonate increases BMD, but doesn’t lower Ca /PTH

cinacalcet (activates CaSR), lowers PTH, lowers Ca, doesn’t change BMD

pneumonia

Hey all,

Here are some notes from a recent morning report on pneumonia. Enjoy!
 

Diagnosis:

·       Hallmark symptoms are cough, fever, sputum production, pleuritic chest pain

·       Physical exam described by Laennec (1819, inventor of stethoscope, died of TB which was diagnosed by nephew with Laennec’s stethoscope)

·       Findings: cachexia (LR 4), vital signs normal (LR .3), asymmetrical chest expansion (LR 44), dullness (LR 3), bronchial sounds (LR 3.3), egophany (LR 4.1)

·       CXR imaging required; pulse oximetry helpful

·       Remember classic lobar, typical bug vs. interstitial, atypical bug is not really useful

·       Can search for microbe with following tests if it will change abx coverage or will likely be positive: blood cultures (+ 10%), sputum culture (14 % useful in all comers, a good sample has < 10 squamous cells / LPF), legionella urine antigen (serogroup 1), pneumococcus urine antigen (70 % sens, > 90 % spec), np swab (60 % sen, 100 % spec), bronchoscopy: consider if immunosuppressed, critically ill, non-responders

Who needs admission/ CURB-65:

·       CURB 65 from Lim W et al, thorax, 2003 (excluded NH residents)

·       Confusion (disorientation to person, place, time), uremia > 7, RR greater or equal to 30, BP < 90 / <=60, age 65 or older.

·       30 day mortality: 0 = .7 %, 1 = 2.1%, 2 = 9.2 %, 3 = 14.5 %, 4 = 40%, 5 = 57%

·       Generally 0,1 for outpt rx; 2s to ward; 3 + to ICU

·       Pneumonia severity index (PSI) stratifies into 5 mortality levels, 3-5s need admission, maybe a bit better at ruling in low risk patients but need !20! variables

·       Remember scores are only a guide, need to consider comorbidities, ability to take meds, hypoxia

Bugs:

·       Strep pneumonia, Haemophilus influenza, Moraxella catarrhalis, staph aureus

·       Atypicals (not on stain): Mycoplasma pneumonia, Chlamydophila pneumonia, legionella species

·       Viruses: A/B influenza, adenovirus, parainfluenza, RSV

·       Anaerobes: only if frank aspiration +- patients with gingival disease

Fun scenarios:

·       Bat/bird droppings: histoplasmosis

·       Exposure to rabbits: F. tularensis

·       HIV/ AIDS: PCP, MAC, histoplasmosis, Cryptococcus and all else

·       Bronchiectasis: pseudomonas, staph, burkholderia cepacia

·       Cough > 2 weeks with whoop or post-tussive vomiting: bordetella pertussis; children or adults with waning immunity

·       Hotel + cruise ship: legionella (from central AC,water towers), first outbreak at legionnaires conference, Philadelphia, 1976

·       Bioterrorism: bacillus anthracis, Yersinia pestis (plague), francisella tularensis (tularemia)

Empirical therapy

·       Outpt / healthy / no abx last 3 months : Macrolide, doxycycline

·       R.Fs for macrolide resistant pneumococcus: old age, recent abx in 3 mos, medical comorbidities, alcoholic, immunosuppressed

·       Outpt / comorbidities / abx in last 3 months (use diff class): resp. FQ or B-lactam + macrolide

·       Inpt/ non-icu: resp FQ or B lactam + macrolide (better survival v. only macrolide)

·       Inpt/ icu: B lactam (3^rd gen cephalosporin) + [macrolide or resp FQ), better survival with double pneumococcus coverage in some studies in really sick pts

·       If worried about pseudomonas i.e alcoholic, frequent abx: use B lactam (that covers pseudomonas and pneumococcus = tazocin, carbapenems, cefipime) + FQ

·       If MRSA: add vanco or linezolid

·       If viral pneumonia: early treatment (within 48 hrs) with oseltamivir, zanamivir recommended by both IDSA + Canadian guidelines, may reduce shedding after 48 hr. N.B remember you can check Ontario respiratory virus bulletin for information about was occurring.

Controversy

·       Cochrane review conducted on antivirals for influenza found lots of problems with data

·       Over 60% of data from phase 3 trials never published, much of it withheld by drug makers

·       42 of 67 studies not used because of discrepancies in data like not including serious adverse events

·       Found antivirals shortened symptom duration by 21 hrs

Management considerations:

·       May not be improving because insufficient time, insufficient dose, resistant bug, wrong diagnosis, metastatic infection (endocarditis, meningitis)

·       Switch to oral therapy when improving, able to tolerate PO, and stable

·       Treat for minimum of 5 days, as long as afebrile for 48-72 hrs + stable

·       Halm E et al Arch Intern Med assessed stability for d/c by using 7 RFs: Temp, HR, RR, sBP, oxygenation, PO intake, mental status. If 2 or more markers at d/c, higher rate of mortality, readmission, any adverse event (OR 7.4)

Hospital acquired pneumonia / healthcare associated pneumonia:

·       Who: Hospitalization within 90 days, NH, home wound care or infusions, dialysis etc.

·       Bugs: gram negative bacilli

·       Drugs: (antipseudomonal drug, PCN, cephalosporin, carbapenem) + FQ + MRSA drug

Ischemic Stroke

Hey all,  today I've posted some notes on ischemic strokes. Enjoy!

Causes of stroke:

·       Embolic (75%): arterial, cardiac, paradoxical, cryptogenic (25 % may be paroxysmal a. fib)

·       Thrombotic (25%): large vessel and small vessel (lacunar)

·       Other causes: dissection, vasculitis, vasospasm

·       DDx: Seizure with todd’s paresis, hypoglycemia

Stroke Syndromes:

·       Opthalmic artery: amaurosis fugax

·       Anterior cerebral artery: hemiplegia (leg > arm), sensory deficits, primitive reflexes

·       MCA: hemiplegia (arm/face > leg), aphasia if dominant hemisphere, neglect if nondominant, gaze towards side of lesion

·       PCA: visual deficits, i.e contralateral homonymous hemianopsia

·       Cerebellar: vertigo, Nx+ Vx, diplopia, dysarthria, ataxia

·       Lacunar: pure sensory or motor loss

·       PICA (posterior inferior cerebellar artery): lateral medulla infarcted, loss of pain +temp contralateral body and ipsilateral face (spinothalamic tract)

Workup:

·       History + physical exam : NIHSS (Nat. institute of health stroke scale)

a.     LOC objective score - alert, response to stimuli

       LOC questions-- how old, what month

       LOC commands-- open then close eyes, grip and release hand

b.     Best gaze (follow my finger)

       Visual fields (confrontation)

       Facial palsy (show me your teeth, raise eyebrows)

c.     Arm motor (extended + palms down, score both)

       Leg motor (raise 30 degrees, score both)

       Limb ataxia (finger to nose, heal to shin);

d.     Sensory (use pinprick)

e.     Best language (describe, name, read)

       Dysarthria (read these words)

       Extinction/inattention (look for neglect)

·       15 items, each scored 0-3/4, > 25 = very severe

·       ABCs, IV, O₂, monitor, neurovitals

·       Screening bloodwork, CXR + ECG

·       Neuroimaging: CT/CTA or MR/MRA. If cannot get vascular imaging then get non-contrast CT

·       Neuroimaging findings: parenchymal hypodensity, swelling causing sulcal effacement + loss of grey/white matter differentiation, hyperdense MCA sign

tPA (tissue plasminogen activator)

·       For acute ischemic stroke within 4.5 hrs of symptom onset, NIHSS > 3 or aphasia

·       .9 mg/kg, to a maximum of 90 mg/kg, 10% bolus then the rest over an hour

·       ASPECTS score for CT scan (if less than 7, usually avoid tPA because of risk of hemorrhage)

·       Endovascular therapy may be an option for patients who do not qualify for tPA because of window, bleeding risk etc.

·       Many contraindications: ICH 6 mos, CVA 3 mos, major Sx, confounding dx, HTN (> 185/110), plts < 100, INR > 1.7

·       tPA can reduce disability in CVA

·       NINDS (1995): tPA within 3 hrs led to better outcome

·       ECAS III (2008): tPA between 3 and 4.5 hrs led to less disability (mRS, NIHSS), NNT 10

·       IST3 (2012): tPA up to 6 hrs- no difference in mortality/morbidity, but perhaps improvement in some risk groups such as older patients (>80), higher NIHSS scores, early Rx

Management:

·       Swallowing screen

·       Remember to think of seizures in periCVA period (10 %); Rx with benzos IV; if one off no other meds, if ongoing then load with anti Sz med

·       Blood pressure: If using tPA then target 185 / 110 to avoid risk of bleed; otherwise target < 220 /120 in order to allow perfusion of penumbra but avoid bleed. Drop by 25 % / 24 hrs, use labetolol or NTG

·       Anti-platelet: ASA 160 mg then daily 82 mg (if tPA wait 24 hrs), if already on ASA switch to Plavix leads to reduced CVA recurrence; can always start ASA, Plavix, or Aggrenox (ASA + dipyridamole)

·       Hemicraniectomy for ICP should be considered in massive MCA strokes where infarct size > 50% territory, GCS less than 8 at 24 hours, worsening imaging etc. to prevent death within 48 hrs

·       Remember for increased ICP: elevate HOB, hyperventilation, hypertonic solution

·       CVA cause workup:

a.     Vascular stenosis (i.e carotid): dopplers/CTA/MRA; endarterectomy if > 50 stenosis, NNT 6 if > 70 %

b.     Arrhythmia: telemetry

c.     ASD/PFO/thrombus: echo

d.     Coagulopathy: coag screen for ALPAs, ATIII, Protein C/S, prothrombin, homocysteine, PNH

e.     Vaculitis: esr, crp, ana, ancas, c3/c4

Long-term management (similar to all secondary CVD mgmt.):

Lifestyle-

·       Healthy diet low in sat. fats, cholesterol, and salt; fruit more than five servings / day

·       Exercise regularly, avoid obesity

·       Stick to safe drinking guidelines; stop smoking

·       Avoid HRTs or OCP in those with CVA

Risk Factors-

·       HTN: aim for less than 140/90; most important risk factor; ACE inhibitor/diuretic combo

·       Hypercholesterolemia: All CVA patients should be on statin, SPARCL study: atorvastatin 80 mg led to NNT 50 to prevent CVA; can target LDL of <2 or 50% reduction

·       Screen for DM, HBA1C > 6.5

·       Screen for OSA, as RF for CVA and consequence of CVA, severe if AHI (episodes/hr) >=30