physio notes - endocrine

7/31/2019 PHYSIO Notes - Endocrine

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CHAPTER

ENDOCRINE SYSTE

Endocrine System 194Thyroid 195Underactivity of Thyroid 196Overactivity of Thyroid 197Parathyroids 198Underactivity of Parathyroids 199Overactivity of Parathyroids 200Adrenal Cortex 201Underactivity of Adrenal Cortex 202Overaetivity of Adrenal Cortex 203Adrenal Medulla 204Adrenaline 205Development of Pituitary 206Anterior Pituitary 207Underactivity of Anterior Pituitary 208Overactivity of Pituitary Somatotroph Cells 209Overactivity of Pituitary Corticotroph Cells 210Panhypopituitarism 211Posterior Pituitary 212Oxytocin 213Antidiuretic Hormone (ADH) 214Underactivity of Posterior Pituitary 215Aldosterone and Antidiuretic Hormone in the

Maintenance of Blood Volume 216Pancreas: Islets of Langerhans 217


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CRINE SYSTEM

DOCRINE SYSTEM

_ HYPOTHALAMUS- I_ - PITUITARYANTERIOR LOBEPOSTER IOR LOBE

-: .--;.u-\\ -

The DUeneSS GLANDSproduce hormones('chemical messengers')which they pass into theblood stream fo r generalcirculation to excite orinhibit the activity of otherorgans or tissues.

Sexualdevelopment andReproduction

Maintenance ofstability of internalenvironment

Resistance to stress

The glands ofinternal secretionare concerned withthe control andcoordination ofprocesses wh ichare widespread inthe body - such asMetabolismFluid balanceGrowth

Al l have a profuse bloodsupply to receive theirsecretions

_ - - THYROID---,,- --- -- 4 PARATHYROIDS

/ 2 TESTES in MaleI (2 OVARIES in Female

" [plus placenta in, pregnancy).),I .I .',,1, I ,.t', I" ,II

_ 2 ADRENALS__ -- Cortex-- ...- - - Medulla-- PANCREAS(Islets ofLangerhans)Some other systems alsoproduce hormones whichare passed into the bloodstream.

STOMACH - GASTRINVIP (pp.75, 86, 96)

SMALL GIP (p.79)INTESTINE SecretinCholecystokinin (CCK)

DIGESTIVE SYSTEM:-

KIDNEYErythropoietinRenin1,25-DHCC (p.198) Hormone molecules may be:proteins, peptides or catecholamines which acton plasma membrane receptors, or they may besteroids or iodinated tyrosine derivatives (p. 195)

which act on receptors in the cell membrane.


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ENDOCR INE SYST

THYRO

Cubical epithelium extracts fromblood stream and concentratesIODIDE (iodide trapping)! - oxidised by peroxidase

IODINE MONOIODOTYROSlinks with (MIT)TYROSINE DJlODOTYROSINE (

DIT+DIT MIT+MIT (6'" '" ( ',0\ / "",0 , '

TRJlODO- ' 0 "' THYRONINE V"" .I'-:e TETRAIODO- (T3) t( j

' " THYRONINE _ (T4) ' :

Stored in colloid when requirel inked with protein a protein-spliTHYROGLOBULIN enzyme relea

FUNCTION:

,Bloodvessels

REGULATION OF SECRETION:

THYROID

Gland weighsabout 25 g in adult

STRUCTURE:2 LOBES (joined by ISTHMUS) composed ofIlie infront ofTRACHEA

T 3 and T 4 are carried by the bloodall body tissues. T 4 is usually convein the cell cytoplasm to T 3 which bto receptors in the nuclei. Thiscomplex binds to DNA and increasspecific genes which increase mRNAand ribosomal RNA and hence protsynthesis. Oxygen consumption,heat production and metabolismincreased. Normal thyroid output isrequired for normal growth.(Para follicula r cells secrete...calci- which lowers blood calcium bysuppressing calcium mobilization frbone and by increasing calciumexcretion in the urine.)BODYTISSUES

THYROID GLANDIncreased O2 consumption is due to an increase in the size and number of mitochondria, inNa + , K + - ATPase activity and the rates of glucose and fatty acid oxidation and synthesis.

.,.--- ....,... TRHfrom/ '" HYPOTHALAMUS,:::..: " FALL in b lood 5: I RISE in blood I,'" THYROID " f THYROID r HORMONES \ -. HORMONES I I depresses pro":,otes I production of'';:; I production of I a I 7iRH d thIII 7iRH d I Q:.,a: an usCl ' an I ::.: lI.i0 I THYROID thus THYROID-: '0 I STlMULATlNG I , / HORMONE (TSH or IHORMONE (TSH) , I y, THYROTROPHIN)0 . I from ANTER IOR ,E \ PITUITARY I from ANTERIOR I : PITUITARY ; decreasesIII \ production " productionen \';;; ' , and release and release " . . . of (THVROIDi of

.........- - -HORMONES-- - - /-1': .: ',.:.' ;.8 .Z1 w , .J


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OCRINE SYSTEM

OF THYROID

I f the thyroid shows atrophy or destruction of its secretory cells or is inadequatelystimulated, the syndrome of hypothyroidism develops because of lack of thyrotrophin-releasing hormone from the hypothalamus or thyroid-stimulating hormone from the anterior pinutary.

Thyroglobulin/,.-'"

x 200Insufficient hormonal secretionreleased to blood stream.Tissue oxidations are depressed,l.e, rate at which cells use energy isreduced.The basal metabolic rate fal ls.Less heat is produced.Body temperature falls (and personfeels cold).Energy units are stored with water.Skin - Thick, leathery, puffy, yellow(due to circulating carotene).Blood cholesterol increases.Appetite is reduced; weight increases.Gut movements sluggish .....constipation.Heart and resp iratory rates and bloodpressure reduced.Thought processes slow down .....lethargy; apathy; somnolence.Hair - bri tt le, sparse, dry.Slow, husky vo ice. Bone marrowsuppressed ..... anaemia

Atrophiedthyroidcells --

Slowing upof allbodilyprocesses

n TSH

Less (or no)Fall (or absence) THYROIDof THYROID HORMONESHORMONES enter blood

,/ in blood \ , to depress \, ' , ' activity of \" ,I I ' ANTERIOR ', I: PITUITARY :\ rr TSH I I, -. ," ,I . Less functional I\ , "... ," t issue to respond

' . . , to THYROID --- 6_ " Body--.- STIMULATING HORMONE Tissues

growth anddevelopment

All 'milestones' of babyhood aredelayed.

Failureofskeletalsexualmental

Grossdwarfing

NB: Protrudingtongue andpot belly.

\IShypothyroidfrom birthis a CRETIN

In the CH ILD - e.g. congenital absence of the glandI CRETINISMA chi ld who

96 THYROXINE (taken by mouth) restores individuals to normal.


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ENDOCRINE SYS

OVERACTIVITY OF THYRO

Commonest form is Graves' disease. Produces increased thyroid hormone secretion(thyrotoxicosis), enlarged thyroid (goitre) and protrusion of eyeballs (exoph th alm os).The disease is caused by production of antibodies against the person's own thyroid cells(i.e. an autoimmune disease). These antibodies, thyroid-stimulating immunoglobulins ( T S I) ,act like thyroid-stimulating hormone ( TSHy and release thyroid hormones (T 3 and T 4) '

x 200

.... Lacunae

Excess thyroid hormones aredistributed by blood stream tothe tissues of the body. ---->Speed up oxidations in thecells . i.e. rate at which all cellsuse energy.The basal metabolic rate israised, more heat is produced----> rise in body temperature(person feels warm).Skin hot and flushed.Profuse sweating.Energy stores of body (i.e.glycogen and fat) are depleted.Appetite increases but weightfalls.Movements of digestive tractare increased ----> diarrhoea.Heart and respiratory rates rise.Blood pressure is raised. A finemuscular tremor andnervousness are marked.Person becomes excitable,irritable and apprehensive.

Hyperplasiaof thyroid - -cells

BodyTissues

Speeding upof allbod ilyprocesses

Great RISE in bloodTHYROIDHORMONES

/ .f \.......- -...-I

Goitre

CVS symptoms very important. T3 and T4 increase cAMP andnumber of padrenergic receptors in heart, thus increase heart'ssensitivity to adrenaline. Blocked by p-receptor blocking agents.[Exophthalmos (protrusion of eyeballs) may be due to an actionof an antibody against a protein of the extraocular musclesand the connective tissue behind the eye which causes thesetissues to swell. It is not due to an excess of thyroid hormones.]

Surgical removal of part or all of the overactive gland or destruction by radioactive iodinereduces the thyroid activity.

THYROIDGLANDtakes up more IODINE[N.B. If the excess thyroxine is formed by tumour tissuethis is outside the negative feedback control of TSH.Similarly TSI are not suppressed by l Thyroxine.]

.....- .. ,," "" \ depresses1 \ ..... production: Formation \ of

I of Th y r o i d , TSH by, Stimulating I M ANTERIOR:/mmunoglobulinst _ PITUITARYI (TSI) ,, I but TSH\ stimulates : does not" greater I affect .\ production ,TSI action

--,and release ",,-_ ......


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OCRINE SYSTEM

But not all tissues are sensitive to It.It plays an importantrole in calc ium andphosphatemetabolism.

,,\

OXYPHIL CELLSwith eosinophilicgranules -function unknown.

,-.

Situatedbehind -,THYROID / -, I',", 2: :, - --:.lOESOPHAGUS I"..Each weighs from

20-50 mg in Adult

Four small glands composed of cords of chief cells which secrete a peptide -\ parathyroid hormone - parathormone or PTH\ '\\ 1CAPILLARIES--, - !General circulation!to all tissues of thebody

GLANDS

Three hormones, parathormone, 1, 25-dihydroxycholecalclferol (1,25-DHCC) and calcitoninact on kidney and gut to keep blood ionized calcium constant (necessary for normalnerve and muscle excitability, blood coagulation and formation of bone and teeth).

Increases Ca in Blood

BONE !/o Stimulates mobilization _ ,oq.1,of , - /9

Ca and " '9"&pol- Inhibited 01)&by Calcitonin

BLOOD STREAM

PTH

KIDNEY,,- ,Increases and I '


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ENDOCRINE SYS

UNDERACTIVITY OF PARATHYROID

Atrophy or removal of parathyroid tissue causes a fall in blood calcium level and increasedexcitability of neuromuscular tissue. This leads to. severe convulsive disorder - tetany .

TROUSSEAU'SSIGN

; '

". _

-'.


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NDOCRINE SYSTEM

OF PARATHYROIDS

Overactivity of the parathyroids (due often to tumour) leads to rise in blood calcium levelwhich may produce renal stones , kidney damage and perhaps osteitis fibrosa cystica.

...."""" ""

(After case by Ashhurst.JOSTEITIS FIBROSA CYSTICAtEventual softeningand deform it y of bonesMultiplebone cysts.

Great increase in concentrationof Ca 2+ in Blood(Plasma Ca 2+ may be over4 mmol/l IncreasedViscosity of Plasma.)Deposition of calcium inunusual sites e.g. kidney.Signs of toxicity(nausea, vomiting, loss

of appetite, etc.)

BONE

1 -

Great lossof P0 43 and Ca 2+in UrineII

KIDNEY , t . -',Greatly increased }

tubular ./reabsorption of Ca 2+ - -and tubularsecretion of P0 43-

GUT. -Great increase in

... absorption of" . dietary Ca 2+.. ' ,,,,,.,

T 1.25-DHCC

UV LIGHT!SKIN!Vitam in Dmetabolites

PARATHYROIDGLANDS Overproduction

of PTH

The increased level of blood calcium eventually leads to excessive loss of calcium inurine (in spite of i reabsorption) and also of water since the salts are excreted in solution.Polyuria, dehydration and thirst result. Most cases are diagnosed before bone diseasedevelops.Excision of the overactive parathyroid tissue abolishes syndrome.


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ENDOCRINE SYS

ADRENAL CORT

The a dr en al c or te x is esse nti al fo r life . It plays an important r ol e i n st at es of stress.There are TWO adrenal glands.They l ie close to the kidneys.

.,

1. MINERALOCORTICOIDSEspecia ll y aldosterone butalso deoxycorticosterone.- ch ief action on kidneytubules.

x 80

LEFTKIDNEY

J' ... .::;, 0(J: : : f : r -t:: 0!iRISE in blood

CORTICOIDS .8 2. GLUCOCORTICOIDS , .. + Especially cortisolo '"' l i t , ; : : :depresses {J 00;: (hydrocortisone) but alsoproduction If This 'tl corticosteroneof e reciprocal . LIVER causes proteinACTH 0 c !ow ;'. catabolism, , ,,:.:: relationsh ip tw A f Amino acids- (5 De een .. 0 ' l"8 and adrenal ,l. f ' so formed are

::J CI) .v used to make.8 .S cortex '" -g leads to # glucose in liver. 'balanced v'" Increases blood sugar.

"8 effects They also have anti-insulin,a o n . anti-inflammatory and anti-allergic actionsare necessary for noradrenalineand adrenaline actions;reduce circulating eosinophils.3. ANDROGENS (sex hormones)Especially dehydroepiandrosteronebut also androstenedione(Oestrogen produced from this in the circulation.Promote protein anabolism and growth (anabolicsteroids). Have minor effects on reproductivefunction.

Stress acts via HYPOTHALAMUS

-DRENAL GLAND

RIGHTKIDNEY

Secretion of aldosterone from the zonaglomerulosa is controlled not only byACTH but also by (a ) A ngiotensin IIreleased by the renin-angiotensin system(page 183) following blood or flu id lossand (b) increase in plasma potassium.

Secretion from the adrenal cortex is underthe control of adreno-eorticotrophic hormonefACTH, corticotroph in ) from the anteriorpituitary (AP) .

Each has an outer CORTEXand an inner :MEDULLA I" ..:r:'::-.

FALL in bloodCORTICOIDS11 \I \" promotes \I product ion ,

I of 'I 'ACTH ,, IIstimu lates, ,\ production , and release ,\ 'of I, "


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DOCRINE SYSTEM

OF ADRE AL CORTEX

Atrophy of the adrenal cortex can be caused by autoimmune disease or destruction bytuberculosis or cancer. Total absence of adrenal hormones is rapidly fatal.

Reduced production ofall cortico ids gives1 'M I ERAlOCORTICOID' EFFECT

II,Incomplete destructionof glands producesADDISON'S DISEASE

'--_ metabolic acidosis'---. Potassium intoxication1 (hyperkalaemia)

Muscular weakness andwasting

(Increase in blood ureaeventually)Excessive loss ofsodium and waterin urine (polyuria)Potassium levelin urine falls.

Blood sodium level falls - ---l.. body f lu id volume decreases(hyponatraemia) (dehydration)1Hydrogen retention Blood volume falls

Potassium retention 1blood pressure fallsI (hypotension)+ i risk ofcirculatory failure

. ' . " ' . '. . . ' . -

.-'." .. ..'- '.

" .,

. Inadequate reabsorption of sodium and;: water..;. and

Reducedtubular: secretion -. of potassium.and hydrogen

1 'ADRENAL A DROGEN' EFFECT: Females show loss of pubicand axil lary hair.

1 'GLUCOCORTICOID' EFFECTII - --- - _ .. Fasting blood sugar level low(hypoglycaemia) . . . may be fatal.Reduced mobilization of proteins and fatcauses lack of energy fo r metabolism.

great mu eular we kness and wasting,great loss of weight, 10 s of ppetite,hypotensionvomiting and abdominal pain,anaemi II RBC formation),pigmentation of exposed and pressureareas of skin (due to rise in ACTH wh ichhas melanophore-stimulatingproperties),1 resistance to stress and infectionsincreased eosinophilsand lymphocytesin blood.

Patients show

.'.c:

- ' . .

. . .'.'. ".GLUCOSE formationfrom PROTEINis depressed / ;9 /

..' ,

.-. .' . , ... .: . .' . .... . , .

M inor stress can produce asudden collapse (Addisoniancrisis). If untreated can be fatal .

Administration of cortisol, a synthetic mineralocorticoid, and sodium chloride restoresindividual to normal.


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ENDOCR INE SYS

OVERACTIVITV OF ADRENAL CORTOveract iv ity or tumour of adrenal cor tex may give excess secretion of any or al l of thecor t icoids:

Altered resistanceto stress

e.g. ALDOSTERONE --- - - - - . " PRIMARY ALDOSTERONISM (Conn's Syndrome)i TUBULAR SECRETION of K+ " Signs of potassium depletionand H+ predominate/ ' .... (lost with water) -----... ! ALKALOSIS MUSCLEExcessive i Blood sod ium - - . . . . . WEAKNESS

reabsorption - I Expanded ECF !of Sodium "\ volume Occasional periodsand \ HYPERTENSION of muscular paralysis\ " ..... ', ! loss of Na" i BP due to nerve blocks'..".' i of K+and W

In urine

Excess glucose: fo rmat ion from. . protein ANTIDIURETIC/ HORMONES


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ENDOCRINE SYST

OXYTOC

OxytocinIncreasesintracellular

Ca 2+ levels

UTERUSLowers threshold fo rdepolarization of musclemembrane.Reinforces contractions ofuterine smooth muscleduring and after chi ldbirth .1Keeps uterus contractedafter placenta is expelled,thus helps haemostasis.

Nerve cells of the- -- -- PARAVENTRICULAR NUCLEUS

send impulses along axons ofPARAVENTRICULOHYPOPHYSEAL- TRACTtoPOSTERIOR PITUITARY

to dischargeOXYTOCIC HORMONE

into BLOOD STREAMfo ron

LACTATINGMAMMARYGLANDS

- - - . ,... HYPOTHALAMUS

--JVULVA

Stimulatesmyoepithelial cellsin ducts to contract!Rapid expression ofpreformed milk fromsecreting alveoli toducts -+ mouth of infant(galactagogue action -or 'Let-down ' of milk)

, -,.-.--. .........._'-.I. ;--_ -_ ... ' i.:-:':':: ;':"':-:-''':-:':::'':::-':-:-:.: -" -

- . NIPPLESof BREASTS

(during SUCKLING)

nerve impulse - - - - - . . tovia spinal cord -+sp inothalamic tract andmidbrain

...fromlTV-I 'I 'I jt{1/,',,II

UTERUS

I,,II

II,IIII

Oxytocin is usedtherapeutically toinduce labour and[0 decrease postpartumbleeding. Its functionin the male is unknown.

Secretion of hormone, OXYTOCIN,seems to depend on afferent(sensory)

dVULVA,(during childbirth

andco itus)


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ENDOCRINE SYSTEM

ANTIDIURETIC HORMONE (ADH)Stimuli fromexternalenvironment

. (e.g. painful . stimuli)andemotional stress

Carotid. aortic baroreceptorsInhibit ?nd receptors

In L. atrium

Stimulate

Nervousreflexes

maintainf luid equilibrium

Increased concentration of plasma sodiumdue tolack of dietary water or toloss of body water f romsweat glands (in sweat)

lungs (in expired air)gut (in faeces)

or toexcess dietary saltresults in!Increased osmotic pressureof blood shrinks stimulates _II osmoreceptors . . - SUPRAOPTIC NUCLEUSNerve cells transmit

'" impulses along axons of. - . SUPRAOPTICOHYPOPHYSEALTRACT to---. POSTERIOR PITUITARYto cause discharge of

ANTIDIURETIC HORMONE (ADH)into BLOOD STREAM fo rdirect action on CELLSLINING DISTAL and COLLECTINGTUBULES of KIDNEYNEPHRONADH increases their, permeability to water" I" Augments reabsorption of" water from glomerular

" , filtrate in' ,DISTAL CONVOLUTEDTUBULE and in COLLECTINGTUBULES!Reduces output of urine tobalance and restore

osmotic pressure

Diminished concentrationof plasma sodium due toe.g. excess intake of water!Dilution of blood stream!Diminished osmoticpressure!Fall in activity ofthe osmoreceptors

!Fall in output of ADH!Diminished reabsorptionof water!Increased output

of dilute urine!Restores osmoticpressurerelationshipsto normal.

ADH binds to V2 receptors on capillary side of duct cells -+ activates adenylate cyclase -+increases cyclic AMP -> activates a protein kinase on luminal side of cell which results inthe insertion of vesicles containing water channels into the apical membrane of the cell ->

214 provides a rapid mechanism for increasing permeability of cell membrane to water.


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ENDOCRINE SYST

UNDERACTIVITY OF POSTERIOR PITUITAR

causes - DIABETES INSIPIDUScharacterized byexcessive productionof dilute urine (polyuria) andexcessive thirst (polydipsia)

Damage. by injury or disease to----- - HYPOTHALAMUS

or to_SUPRAOPTICOHYPOPHYSEAL TRACT--- -,Absence fromblood stream ofANTIDIURETIC HORMONE(ADH)

I f pituitary gland aloneis removed ADH continuesto be secreted from cutaxons.

from - - - Normal glomerularfiltrate - of about 180 litresper day.of - - - - about 140 litres of

glomerular filtrate wateris outside theinfluence of ADH.

Increased elimination, / o fwa te r. ;"

REABSORPTION - - - - of - - - - about 40 Iitres per dayfromDISTAL CONVOLUTEDTUBULE and COLLECTING - - - - - normally under ADH control.DUCT is reduced.(Cells lining collecting ductremain impermeable to water)

REABSORPTION - - - -from'PROXIMAL CONVOLUTEDTUBULE and loop of HENLE

Diminishedreabsorption of water - - -

Urinary volume rises -- Usually 4-6 Iitres but canbe 12-15 l itres of paledilute urine excreted/day(about 200 mOsm!l)instead of normal Iitresstraw coloured moreconcentrated fluid(1000-1400 mOsmfl)

Constant thirst - - - - occurs

Replacement of ADH restores the elimination of water and symptoms of thirst to normal.


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ENDOCRINE SYSTEM

ALDOSTERONE AND ANTIDIURETIC HORMONE (ADH)IN THE MAINTENANCE OF BLOOD VOLUME

A reduction in the total volume of extracellular fluid (e.g. after haemorrhage or loss ofisotonic secretions from the gut in vomiting or diarrhoea) leads to chain of compensatorymechanisms in which aldosterone plays an important role. See pages 183 and 185.

HYPOTHALAMUS -+ increasesformation of ADH

and its releasefrom POSTERIOR...... PITUITARY

e.g.

Vasoconstriction :.-"""-'


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ENDOCRINE SYS

PANCREAS: ISLETS OF LANGERHANISLETS OF LANGERHANS make up 1-2% of pancreatic tissue. Consist of four celltypes: A(oc) secrete glucagon, B(P) secrete insulin, D (c5) secrete somatostatin, F secretepancreatic polypeptide (regulates release of digestive enzymes of pancreas).

-+ glucose

ACTIONSTBLOOD GLUCOSE when i tfalls below normal.!Promotes conversion in liverglycogenlactic acid

amino acidsi.e. protects againsthypoglycaemia.

TBLOODGLUCOSE!! GLUCAGON

!BLOOD....- GLUCOSE!l INSULlN

T BLOOD GLUCOSEafter a meal!TINSULIN .

x

A cel ls secrete GLUCAGON ---_ " (25%)

CONTROL!BLOOD GLUCOSE(fasting = 5 mmolf l).!TGLUCAGON!\ Breakdown of\ GLYCOGEN" ACTIONSB cells (50-75%) secrete INSULIN - - ! BLOOD SUGAR

CONTROL is by 'negative feedback' with BLOOD Accelerates: glucose into skeletalGLUCOSE muscle; synthesis of proteins.Converts: glucose -+ glycogen(glycogenesis); glucose etc. -+fatty acids (lipogenesis).Decrease in liver: glycogen -+ glucose(glycogenolysis) other nutrients -+glucose (gluconeogenesis).

==:::::===_inhibits GLUCOSE UTILIZATION promotes FAT UTILIZATION Ti BLOOD SUGAR (may reach! 28 mmolfl)Renal threshold exceeded!-- TT Free fatty GLUCOSE in URINE (lost inacids and ! solution with H20 )ketone Polyuria and polyphagiabodies in \...blood ==;:-......................... THIRST++ -> polydipsia! pH (acidosis) KETONE BODIES in URINE

ATROPHY of ISLETS _ ABSENCE OF INSULINDIABETES MELLITUS /!! rate of glucose transport acrosscell membranesTT UTILIZATION of GLUCOSE by MUSCLETT MOBILIZATION andUTILIZATION of DEPOT FATinstead of glucose

+FAT STORES depletedFAT DEPOSITS in BLOOD VESSELS(atherosclerosis)TT GLUCONEOGENESIS-+DEPLETION of BODY PROTEIN -> muscle wasting andloss of weight;

fatigue readily.If untreated -+ progressive drowsiness -+ coma -> death.Excess insulin (hyper insulinism) -- low blood sugar (hypoglycaemia) -- irritability;

physio notes - endocrine

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