Pituitary gland disorders and anesthetic management

PITUITARY GLAND DISORDERS AND

ANESTHETIC MANAGEMENT

PRESENTER : DR UNNIKRISHNAN P.COORDINATOR : DR MAYA

MODERATORS: DR JAYAKUMAR DR RAVI

.BASICS HYPO PITUITARISM

TUMORSTRANS

SPHENOIDAL SX

DI /SIADH

WE HAVE TO

• optimize the patient undergoing the surgery

WE HAVE TO

• take care of the patient perioperatively

ANATOMY

.

.

SOMATOTROPES 50%MAMMOTROPES 25%CORTICOTROPES 15%THYROTROPES 10%GONADOTROPES 10%NULL CELLS

GHPROLACTINACTHTSHLH & FSHINERT

ANATOMY

ANATOMY

CONTROL OF PITUITARY FUNCTION

.CORTICOTROPIN RELEASING HORMONE

THYROTROPIN RELEASING HORMONE

GROWTH HORMONE RELEASING HORMONE

GROWTH HORMONE INHIBITING HORMONE[SOMATOSTATIN]

GONADOTROPIN RELEASING HORMONE

PROLACTING INHIBITING HORMONE

↑ACTH

↑TSH & PROLACTIN

↑GH

↓GH &TSH

↑LH & FSH

↓PROLACTIN

DISORDERS OF PITUITARY FUNCTION

HYPOPITUITARISM

AETIOLOGY

DEVELOPMENTAL: KALLMANN SYNDROME

TRAUMATIC: SURGERY RADIATION HEAD INJURY

NEOPLASM : PITUITARY ADENOMA CRANIOPHARYNGIOMA RATHKE’S CYST METASTASIS

INFILTRATORY / INFLAMMATORY : SARCOIDOSIS

VASCULAR : PITUITARY APOPLEXY SHEEHANS SYNDROME

INFECTION

CLINICAL FEATURES

GH LH&FSH ACTH

TSH PL,VP

CLINICAL FEATURES

COMA• HYPOGLYCEMIA/WATER INTOXICATION /HYPOTHERMIA

TUMOR COMPRESSION• HEADACHE VISUAL FIELD DEFECTS

LAB DIAGNOSIS

• P R I N C I P L E :• DEMONSTRATE LOW LEVELS OF

TROPIC HORMONES IN THE SETTING OF LOW TARGET HORMONE LEVELS..

LAB DIAGNOSIS

HORMONE TESTSGROWTH HORMONE INSULIN TOLERANCE TEST, GHRH

TEST, L-DOPA TEST

PROLACTIN TRH TEST

ACTH INSULIN TOLERANCE TEST METYRAPONE TEST , ACTH STIMULATION TEST

LH/FSH GnRH TEST

COMBINED ANTERIOR PITUITARY TEST

TREATMENT

DEFICIENCY REPLACEMENT

ACTH HYDROCORTISONE 10-20 MG AM 5-10 MG PM

TSH L-THYROXINE 0.075-0.15 MG DAILY

FSH / LH males TESTOSTERONE ENANTHATE 200MG IM EVERY 2 WEEKS

females CONJUGATED OESTROGEN 0.65-1.25MG QD X 25 DAYS

GH SOMATOTROPIN 0.1-1.25 MG SC QD

VASOPRESSIN INTRANASAL VASOPRESSIN 5-20µG BD

STEROID REPLACEMENT

CURRENTLY TAKING STEROID

<10 MG QD[PREDNISOLONE]

ASSUME NORMAL HPA AXIS

ADDITIONAL STEROID COVER NOT REQUIRED

>10MG QD MINOR SURGERY

25MG HYDROCORT. AT INDUCTION

MODERATE SURGERY

USUAL PREOP.DOSE + 25MG HYDROCORT. AT INDUCTION + 100MG/ DAY FOR 24 HRS

MAJOR SURGERY

USUAL PREOPERATIVE STEROID + 25 MG HYDROCORTISONE AT INDUCTION +100MG/DAY X 48-72 H

HIGH DOSE

GIVE SAME

STOPPED

< 3 MS TREAT AS IF ON STEROIDS

>3 MS NO PERIOP. STEROID

STEROID SUPPLIMENTATION[Miller/7/e]

SURGERY HYDROCORTISONE

MAJOR 200 MG/DAY PER 70 KG

MINOR 100 MG/DAY PER 70 KG

DECREASE THE DOSE BY 25%/DAY UNTIL ORAL FEEDS START, THEN USUAL MAINTENANCE DOSE

PITUITARY TUMOURS

TYPES• ADENOMAS ARE THE COMMONEST

CAUSE OF ABNORMAL ENDOCRINE PITUITARY FUNCTION

• 10-15% OF ALL INTRACRANIAL TUMORS• MOST ARE BENIGN; 50% PROLACTINOMAs

CELL TYPE HORMONE SYNDROME

LACTOTROPE PROLACTIN HYPOGONADISMGALACTORRHOEA

GONADOTROPE FSH / LH HYPOGONADISM

SOMATOTROPE GH ACROMEGALYGIGANTISM

CORTICOTROPE ACTH CUSHINGS DISEASE

EFFECTS

IMPACTED STRUCTURE CLINICAL IMPACT

PITUITARY HORMONAL IMBALANCE

OPTIC CHIASMA VISUAL FIELD ABNORMALITIESOPTIC /OCULOMOTOR

HYPOTHALAMUS TEMPERATURE DYSREGULATIONAPPETITE/THIRST DISORDERSOBESITY DIABETES INSIPIDUS

CAVERNOUS SINUS OPHTHALMOPLEGIA

FRONTAL LOBE PERSONALITY DISORDER

BRAIN HEADACHE HYDROCEPHALUSEPILEPSY

EVALUATION AND DIAGNOSIS IN GENERAL

BASAL PROLACTIN LEVELS, TFT

HIGH QUALITY MRI

OPHTHALMIC EVALUATION NECESSARY

TREATMENT : DEPENDS ON TUMOR

SURGERY /RADIATION/MEDICAL

Craniopharyngiomas

• are benign, suprasellar cystic masses that present with headaches, visual field deficits, and variable degrees of hypopituitarism. They are derived from Rathke's pouch and arise near the pituitary stalk

RATHKE’S CYSTS

• Developmental failure of Rathke's pouch obliteration may lead to Rathke's cysts

• compressive symptoms, diabetes insipidus, and hyperprolactinemia due to stalk compression

ACTH SECRETING TUMORS

CLINICAL CONDITION RESULTING FROM INCREASED ACTH SECRETION BY PITUITARY ADENOMA-”CUSHINGS DISEASE”

MOST ARE MICROADENOMAS

MORE IN WOMEN

EARLY DIAGNOSIS

ACTH SECRETING TUMORSMOONS FACE BUFFALO OBESITYPROXIMAL MYOPATHY OSTEOPOROSIS VERTEBRAL COLLAPSESTRIAE HIRSUITISM ACNEDIABETES HYPERTENSION LVHHYPERNATREMIA HYPOKALEMIA ALKALOSISOSASGERDRENAL STONE MENTAL DISTURBANCE

ACTH SECRETING TUMORS

DIFFERENCE FROM ECTOPIC ACTH PRODUCING TUMORS: SLOW ONSET, HYPOKALEMIA LESS INTENSE,HIGH DOSE STEROID CAN SUPPRESS CORTISOL SECRETION UNLIKE AS IN ECTOPIC PRODUCTION OF CORTISOL

ACTH SECRETING TUMORS

DIAGNOSIS

URINARY FREE CORTISOL

HIGH DOSE DEXAMETHASONE SUPPRESSION TEST [2MG Q6H X 48h]

CRH TEST EXAGGERATED RESPONSE

ACTH UNDETECTABLE10-100 ng/L>200 ng/L

ADRENAL TUMORPITUITARY DEPENDENTECTOPIC ACTH SECRETION

ACTH SECRETING TUMORS

TREATMENT

SURGERY-CURATIVE IN <80%

PRETREATMENT WITH METYRAPONE/BETACONAZOLE REVERSES EFFECTS OF EXCESS CORTISOL AND DECREASE PERIOPERATIVE MORBIDITY

ACTH SECRETING TUMORS PERIOPERATIVE CONCERNS

BLEED EASILY

TENDS TO HAVE HIGH CVP

PROPER Rx OF HTN AND DM

ENSURE NORMAL INTRAVASCULAR VOLUME & ELECTROLYTES

OSTEOPENIAHIGH CHANCE OF FRACTURES CAREFUL POSITIONING

IMMUNOSUPPRESSION / INFECTION

PROLACTINOMAS

>50% OF FUNCTIONING TUMOURSMAJORITY ARE MICROADENOMAMORE IN WOMEN [90%]2º AMENORRHOEA,

INFERTILITY,GALACTORRHOEAMACROADENOMA MORE IN MENPRESSURE EFFECTS MAIN SYMPTOMPROLACTIN >400 mU/ L

PROLACTINOMAS:RxM E D I C A LFIRST LINE;CURATIVE IN UPTO 95%CABERGOLINE [LONG ACTING]BROMOCRIPTINE [SHORT ACTING]S U R G I C A LONLY IF DOPAMINE

RESISTANCE/SIDE EFFECTSINVASIVE ADENOMA,

COMPROMISING VISION

ACROMEGALY

GH GH GH everywhere…

GH hyper secretion from a pituitary macroadenoma

If occurs before epiphyseal fusion Gigantism

After epiphyseal fusionAcromegaly

Clinical FeaturesFACE

HANDS&FEET

MOUTH&TONGUE

SOFT TISSUESKELETAL

CVS

ENDOCRINEOTHERS

INCREASE IN SIZE OF SKULL AND SUPRAORBITAL RIDGESENLARGED MANDIBLE *large blade*INCREASE IN SPACING BETWEEN TEETH MALOCCLUSSIONSPADE SHAPED CARPAL TUNNEL SYNDROMEINCREASED HAND AND FOOT SIZE *SpO2 probe*MACROGLOSSIA ,THICKENED PERI EPIGLOTTIC FOLDS AND LARYNGEAL SOFT TISSUES SMALL LARYNGEAL APERTURE *difficult laryngoscopy* OBSTRUCTIVE SLEEP APNOEATHICK SKIN DOUGH LIKE FEEL TO PALMVERTEBRAL ENLARGEMENT KYPHOSISOSTEOPOROSISHYPERTENSION CARDIOMEGALY LV DYSFUNCTIONIMPAIRED GLUCOSE TOLERANCE, DIABETESARTHROPATHY, PROXIMAL MYOPATHYTHYROID ENLARGEMENT *tracheal compression*RLN PALSY

DIAGNOSIS

24 H GROWTH HORMONE LEVELS

ELEVATED S.IGF LEVELS

ORAL GLUCOSE TOLERANCE TEST

FAILURE OF GROWTH HORMONE SUPPRESSION TO TO <1µG/L WITHIN 1-2 HRS OF AN ORAL GLUCOSE LOAD 75G

TREATMENT

SURGICAL RESECTION [cure rate upto 70%]Soft tissue swelling improvesGH level returns to normalIGF-1 levels normalisedComplication : hypopituitarism ,recurrence

TREATMENT

MEDICALDopamine agonists: Bromocriptine, CabergolineSomatostatin Analogues: Octreotide ,Lanreotide

preoperative shrinkageGH receptor antagonist : Pegvisomant

PRE ANESTHETIC CHECK-UPDETAILED & CAREFUL AIRWAY ASSESSMENTINDIRECT LARYNGOSCOPYOSAS : SNORING , DAYTIME SLEEPINESSCENTRAL RESPIRATORY DEPRESSIONPERIOPERATIVE AIRWAY COMPROMISE : RISK OF DEATH IS 3 FOLD HIGHHYPERTENSION : ARRHYTHMIAS,CCF CHECK ANTIHYPERTENSIVESLV DYSFUNCTIONDIABETES MELLITUS [IN 50%]VISUAL FUNCTIONRAISED ICPHORMONAL FUNCTION: CHECK RECENT REPORTS / OPTIMIZE

SURGERY

APPROACHES

TRANS SPHENOIDAL

TRANS ETHMOIDAL

TRANS CRANIAL

WHY TRANSSPHENOIDAL APPROACH

RAPID ACCESS

LESS TRAUMA,

LESS BLEEDING

LESS COMPLICATIONS

OTHER APPROACHES

TRANS FRONTAL : IF SUPRASELLAR EXTENSION / POSTOP SEIZURES

PTERIONAL CRANIOTOMY

TRANSCRANIAL : IF SMALL SPHENOID;S/E HIGH CHANCE OF HYPOPITUITARISM

REMEMBER TO GIVE..

HYDROCORTISONE 100 MG• .

PROPHYLACTIC ANTIBIOTICS• .

ACCESSING THE AIRWAY… BAG & MASK VENTILATION: MAY NEED OROPHARYNGEAL AIRWAY

4 GRADES OF AIRWAY INVOLVEMENT

GRADE 3 & 4 : TRACHEOSTOMY

FIBREOPTIC LARYNGOSCOPY

GRADE 1 NO SIGNIFICANT INVOLVEMENT

GRADE 2 NASAL & PHARYNGEAL MUCOSA HYPERTROPHY

GRADE 3 GLOTTIC STENOSIS / VOCAL CORD PARESIS

GRADE 4 2&3 i.e. GLOTTIC & SOFT TISSUE INVOLVEMENT

SO BE READY WITH……• LARGER FACE MASKS• LONG BLADED LARYNGOSCOPS• ILMA• FIBREOPTIC LARYNGOSCOPE IF AVAILABLE• TRACHEOSTOMY SET• N.B.NASAL INTUBATION HAZARDOUS IF

PREVIOUS TRANSSPHENOIDAL SURGERY HAS BEEN DONE

POST INTUBATION

LUMBAR DRAIN IF SUPRASELLAR EXTENSION

10 ML ALIQUOTES OF .9% SALINE SUPRASELLAR PART PROLAPSES INTO FIELD

PACK THE MOUTH AND POSTERIOR PHARYNX

↓LARYNGOSPASM ↓PONVPOSITION TUBE TO ALLOW ACCESS TO THE INCISION SITE

TRANSSPHENOIDAL ROUTEENT SURGEON WILL ASSIST NEUROSURGEON

XYLOMETAZOLINE SAFER FOR PREPARATION OF NASAL MUCOSA

SUPINE

MODERATE DEGREE HEAD UP / CAUTION:IF >15º

HEAD SLIGHTLY TURNED {CAUTION : NECK VEINS ? OBSTRUCTION}

SURGEON BEHIND THE HEAD OR TO THE RIGHT OR LEFT

ETT & BAINS CIRCUIT AWAY FROM FIELD

C-ARM : WEAR LED APRON

.• .

.

INTRAOPERATIVE PERIOD

.EFFECT OF AGENTS ON SECRETION OF HORMONES NOT A BIG CONCERN

↑ ICP : ? TIVA BETTER ? AVOID NITROUS OXIDE

SHORT ACTING AGENTS HASTEN RECOVERY AT END { PROPOFOL, SEVOFLURANE ETC}

VENTILATE TO NORMOCAPNOEA

PERIODS OF INTENSE STIMULATION : SHORT ACTING OPIOID

PATIENT SHOULD NOT WAKE UP WITH PAIN ? IV MORPHINE 20’ BEFORE ENDB/L MAXILLARY NERVE BLOCK PREVENT HYPERTENSIVE RESPONSE DURING GA

EXAGGERATED RESPONSE TO EPINEPHRINE [ WITHOUT HALOTHANE]

TEMPERATURE DYSREGULATION

HYPOGLYCEMIA

ABNORMAL ENDOCRINE FUNCTION

CHANCE OF CAROTID ARTERY INJURY

.

.

MONITORS

VEP:HIGH FALSE +/-

ETCO2

ECG SpO2

VAE

IBP

COMPLICATIONS

TRANS SPHENOIDAL

TRANS CRANIAL

INJURY TO CAROTIDINJURY TO PONS

FRONTAL LOBE ISCHEMIC DAMAGEINJURY TO OPTIC CHIASMAPOST OP SEIZURES [SUBFRONTAL]ANOSMIA

EXTUBATION

RAPID & SMOOTH EMERGENCE NEEDED FOR NEUROLOGICAL ASSESSMENTSUCTION UNDER DIRECT VISIONREMOVE THROAT PACK ; BUT DON’T DISLODGE NASAL PACKS & STENTSRETURN OF RESPIRATION,LARYNGEAL REFLEXES OBEYING TO VERBAL COMMANDSEXTUBATION

Postoperative concerns….

AIRWAY

BLOOD IN ORO AND NASOPHARYNX

NASAL PACKS

PREDISPOSITION TO AIRWAY OBSTRUCTION

NASAL CPAP CANT BE APPLIED

NARCOTICS WITH CAUTION

Post operative concerns… ANALGESIA

PAIN : TRANSSPHENOIDAL-MODERATE TRANSCRANIAL-MORE INTENSE

NASAL PACK-DISTRESSING

CODEINE

MORPHINE i.m.

MORPHINE PCA

Post operative concerns..

ENDOCRINE MANAGEMENT

HYDROCORTISONE 50-50,25-25,20-10[6pm]

Prolactinoma :few days / Cushing's :few months

ENDOCRINOLOGY REVIEW

POSTOPERATIVE COMPLICATIONS

DIABETES INSIPIDUS

SUSPECT IF URINE O/P >2mL/Kg/h & S.Na >143 mmol/L

POLYURIA,THIRST

SEND PLASMA OSMOLARITY [>295mosm/Kg] AND URINE OSMOLARITY [<300 mosm/Kg]

POSTOPERATIVE COMPLICATIONS:D.I.

IF AWAKE AND NORMAL THIRST: FLUIDS

COMA/THIRST MECHANISM ABOLISHED/VERY HIGH URINE VOLUMEDESMOPRESSIN ACETATE [DDAVP]

PROBLEM:HYPONATREMIA

USUALLY RESOLVES IN FEW DAYS

POSTOPERATIVE COMPLICATIONS

HYPONATREMIA

CAUSES : DDAVP Rx, SIADH

MONITOR S.ELECTROLYTES

FLUID RESTRICTION

USUALLY RESOLVE WITHIN 10 DAYS

NATRIURESIS+DIURESIS CEREBRAL SALT WASTING SYNDROME

DD: SIADH

POSTOPERATIVE COMPLICATIONS

SIADH: WATER RETENTION Rx : WATER RESTRICTION

CSW Rx : HYPERTONIC SALINE

POSTERIOR PITUITARY

DIABETES INSIPIDUSEXCRETION OF ABNORMALLY LARGE AMOUNTS OF DILUTE URINE

24H URINE VOLUME >50ML/KG AND OSMOLARITY <300MOSM/L

URINARY FREQUENCY,NOCTURIA, DAY TIME FATIGUE, POLYDIPSIA

COMPLETE D. INSIPIDUS

NEOPLASM

CNS DISORDERS

PULMONARYDRUGS

POST-OP

CA BRONCHUS-SMALL CELL CA,CA PANCREAS,CA PROSTATEMENINGITIS,HEAD INJURY,CVA,HYDROCEPHALUS,GBSTB , PNEUMONIACHLORPROPAMIDE ANTIDEPRESSANTSHALOPERIDOL CARBAMAZEPINE CHEMOTHERAPY THIAZIDES MORPHINE NSAIDSPAIN NAUSEA

CAUSESC R A N I A L / N E U R O G E N I C

IDIOPATHIC

TRAUMA / POST SURGICAL

TUMOUR

VASCULAR [SHEEHAN’S SYNDROME,AORTO-CORONARY BYPASS]

GRANULOMA

INFECTIONS

FAMILIAL

N E P H R O G E N I C

GENETIC

METABOLIC : HYPOKALEMIA , HYPERCALCEMIA

DRUG : LITHIUM , DEMECLOCYCLIN

POISONING :HEAVY METAL

POST OBSTRUCTIVE : PROSTRATE , URETERAL

VASCULAR : SICKLE CELL DISEASE

INVESTIGATIONS• WATER DEPRIVATION TEST

WATER DEPRIVATION

PITUITARYVASOPRESSIN

EXOGENOUS VASOPRESSIN

NORMAL NO EFFECT

D.I.INCREASE IN URINE

OSMOLARITY

TREATMENT

•5u / mL im

•Q48H

PITRESSIN TANNATE

•50 u / mL in isotonic saline

•DRODID nasal spray

SYNTHETIC LYSINE

VASOPRESSIN

•1-2µg bd iv or s/c

•10-20 µg bd/tid nasal spray

•100-400 µg bd / tid orally

DESMOPRESSIN

DESMOPRESSIN

1-Deamino 8-D Arginine VasoPressin [DDAVP]ONSET 15 MIN AFTER INJ, 60 MIN AFTER

ORALACTS SELECTIVELY AT V2 RECEPTORS TO

INCREASE URINE CONCENTRATIONOTHERS:THIAZIDES/CHLORPROPAMIDE

CARBAMAZEPINE

CLOFIBRATE

PERIOPERATIVE MANAGEMENT

POST HYPOPHYSECTOMY

• RECOVER IN FEW DAYS TO 6 MONTHS

POST HEAD TRAUMA / POSTSURGERY• RECOVER AFTER A SHORTER PERIOD

COMPLETE D. INSIPIDUSJUST BEFORE SURGERYUSUAL DOSE INTRA NASALLY OR aq.VASOPRESSIN 100 mU IV BOLUS F/B CONSTANT INFUSION OF 100-200 mU/HR

ISOTONIC IVFs

P.OSMOLARITY HOURLY

IF >290 mOsm/L HYPOTONIC IVFs INCREASE VASOPRESSIN INFUSION >200 mU/ HR

PARTIAL D. INSIPIDUS

POST OPERATIVELY, INTRANASAL VASOPRESSIN / PITRESSIN TANNATE 5-10 U /DAY IM

VOLUME DEPLETION Sx STRESS ADH

SECRETION

CONCERNS: VASOPRESSIN

OXYTOCIC PROPERTIES [CAUTION PREGNANCY]

CORONARY VASOCONSTRICTOR [CAUTION CAD]

STICK TO CORRECT DOSE

SIADH

WATER OVERLOAD, LOW SERUM OSMOLARITY,HYPONATREMIA…STILL..

PERSISTENT ADH SECRETION

MORE WATER RETENTION

CLINICAL FEATURESWEIGHT GAIN

LETHARGY

CONFUSION

ABNORMAL REFLEXES

CONVULSION

COMA

….FEATURES OF HYPONATREMIA AND BRAIN EDEMA

DIAGNOSISPatient with hyponatremia excrete urine which

is hypertonic relative to plasma….

DIAGNOSISURINE Na >20 mEq/lLOW BUN , S.CREATININE, S.URIC ACID , S. ALBUMINS.Na <130 mEq /LPLASMA OSMOLALITY <270 mOsm /LHYPERTONIC URINE RELATIVE TO PLASMAUNABLE TO EXCRETE URINE EVEN AFTER WATER LOADINGADH ASSAY IN BLOOD

N.B. : PATIENTS SUSPECTED FOR SIADH SHOULD BE SCREENED FOR ADRENAL INSUFFICIENCY & HYPOTHYROIDISM

TREATMENTMILD-MODERATE SYMPTOMS

RESTRICT FLUIDS 500-1000 ML/ DAY

SEVERE

5% SALINE IV 200-300ML OVER SEVERAL HRS FOLLOWED BY FLUID RESTRICTION

Rx UNDERLYING PROBLEM

TREATMENTDRUGS

PHENYTOIN ,NALOXONE ,BUTORPHANOL

EFFECT ON RELEASE -CLINICALLY INEFFECTIVE

LITHIUM BLOCK EFFECT OF ADH ON RENAL TUBULES ,TOXICITY > BENEFITS

DEMETHYL CHLORTETRACYCLINE 900-1200 mg/day interfere with ability of renal tubules to concentrate urine

PERIOPERATIVE MANAGEMENT

CONCERNS

ANEMIAMALNUTRITIONFLUID &ELECTROLYTE IMBALANCELOW URINE OUTPUTDELAYED AWAKENINGMENTAL CONFUSION

.

• CVP PAC• TEECENTRAL

VOLUME

• URINE & PLASMA OSMOLARITY

• S. Na FREQUENT

ASSAY

ALSO NOTE…..

USUALLY ONLY FLUID RESTRICTION IS NEEDED ; RARELY, HYPERTONIC SALINE

AGE OF PATIENT AND TYPE OF ANESTHETIC AGENT HAVE NO BEARING WITH INCIDENCE OF SIADH

REFERENCES ANESTHESIA AND UNCOMMON DISEASES, FLEISHER,5/e PITUITARY DISEASE AND ANESTHESIA,M.SMITH & N.P

HIRSH,BJA, 85 (1) 2000 STOELTING’S ANESTHESIA & COEXISTING DISEASE, 5/e HARRISONS PRINCIPLES OF INTERNAL MEDICINE,17/e LEE MCGREGOR’S SYNOPSIS OF SURGICAL

ANATOMY,12/e REVIEW OF MEDICAL PHYSIOLOGY,WILLIAM F

GANONG,22/e

.

READING UNCOMMON THINGS WHICH WE HAVENT FACED YET MAY WASTE TIME….

FACING UNCOMMON THINGS

WHICH WE HAVENT READ YET

MAY WASTE LIVES….