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SINHLYHOC

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T~PII

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SINH LYHOC

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TRUONG £)AI HOC Y HA NOI

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80 MON SINH L Y HOC

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SINH LYHOC

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TAP II

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(Tai ban l§.n thu hai co sua chua)

NHA XUAT BAN Y HOC HA N(>I- 2005

CHU BIEN

PGS. TRJNH BINH DY

THAM GIABIEN SO~N PGS. TRJNH BINH DY

GS. TS. PHAM THJ MINH Due

TS. PHUNG XUAN BiNH

TS. TRJNH HUNG eUONG PGS. TS. LE THU LIEN

LOINCHDAU

Sinh ly hoc la man h9C co so ctia y hoc. Sinh ly h9C y h9C cliuyen ngliien CII:U v~ lioat d(Jng cliuc nang cua cac te bao, cac co quan, h~ thong co quan trong uuii lien h~ giiia cluing oai nluiu va. giiia cluing ooi moi truang song, dong thai ngliien. cuic ve sl_t dieu lioa cliuc nang de' dam biio cho co the ton t.ai, pluit trieti va tliicli ung duoc oai slj bien do'i ctia nuii truang.

Sacli guio klioa sinh ly h9C xu/it ban ldn. nay nlui ni cung ctip clio sinh uieti y nluing ltien. th.uc co ball ve sinh ly hoc de' otin dung VaG cac man y h9C 10.111 sa ng cling nliu y h9C dlj pliong. Scicli ciini; co tId dutu; lam tai li~u tluim kluio clio ctu: h9C uien. sau dai h9C cliuyen. nganli y lioc. Sacli trinli bay nluTng die'IrL co ban nluit nuuig tinli cqp nluit va co so lieu ciio Vi~t Nani.

Trong thai dai bung no' thong tin Ilgay nay, nluing tien b(J cua klioa hoc Ily tluuit 111011 dent lai nluing hien tliuc nuii ch o sinh ly hoc va thea thai gian se co nluing kluii uiem nuii, dinli ngliia 1I1.6i, boi ('(IY CII: ba (ten ruini tuiin ctin duac xu/it ball lai de C¢.P nluit hen tliuc 1716i.

Clui bien va ban bien soan cuon sa clt nay La uluing can b¢ ltiu ruini ctia b¢ man do. c6 nliieu cong trinli ngliien ctiu kh oa h9C, dii guiiig va bien soon sacli guio Iehoo. sinh ly h9C, dO. tliani gia lam cong to!' cluin doan ta: ctic b~nh oien oii tliuaug xuycn. tiep xuc uai nganli sinh ly h9C y hoc II1l6c ngoai.

Trong qua trinli bien soan. va xtui.i ban nuic du dii c6 uliieu. co' gdng nliung cluic cluin can c6 thiCu s6t, cluing toi niong nluin duoc nliiing y kien dong gop ctui ctic dong ngliiep ua ban doc.

GS.TS. PH~ THI ~INH Due 'I'rudng BQ mon Sinh ly hoc Truong Dl?i hoc Y Ha NQi

CHUaNG 6

QuA TRINH T~O NtfOC TIEU 0 TH~N

8V tao thanh nude ti~u d than g6m hai qua trinh:

- Qua trinh 19C d diu than: mot phan huyet tuong duoc 19C qua mao mach VaG b9C Bowman va trd thanh dich 19C cau than.

- Qua trinh tai hap thu va bai tiet d 6ng than: khi dich 19C di xuong 6ng than, th~ tich va thanh phan cua dich 19c se bi thay deli. Nude va mot so' chat hoa tan duoc dua trd lai mau nho qua trmh tai hap thu. Nguoc lai, mot so' chat hca tan duoc bai tie't VaG dich 6ng than d~ tao thanh nude ti~u.

Nhu v~y thong qua chuc nang tao nude ti~u, than giup co th~ gift lai nude, cac chat di~n giai va cac chat chuyen h6a quan trong, dong thoi dao thai nhimg san pharn c6 hai nhu ure, creatinin, acid uric,v.v. Thanh phan cua nude ti~u c6 th~ thay deli do co rat nhieu cd che dieu hoa hangtinh noi moi nharn gift cho thanh phan cua dich ngoai bao duoc hang dinh bang each thay deli IUQng nude va cac chat hoa tan trong nude ti~u.

GIA.I PHAU SINH LY TH!N

Don vi giai phau va chuc nang cua than la nephron. Moi nephron deu c6 kha nang tao nude ti~u. Do do khi ta mo tii chuc nang cua mot nephron cling la mo ta chuc nang cua than. Moi than chua khoang tu 1 de'n 1,3 trieu nephron.

Nephron g6m cau than va 6ng than (Hinh 6-1). Mau di VaG cau than qua ti~u dong' mach de'n va roi khoi cau than bang' ti~u dong' mach di. Cau than la mot bui mao mach g6m tren 50 nhanh mao mach song song. Cac mao mach n6i thong nhau va duoc bao b9C trong bao Bowman. Ong than g6m 6ng IUQn gan, quai Henle, 6ng IUQn xa va 6ng gop.

Cau than va 6ng IUQn gfrn narn d vung va than. Quai Henle narn sau trong khdi than. M9t so' quai Henle di VaG tan day cua vung tuy than, Quai Henle g6m hai nhanh, nhanh xuong va nhanh len. Thanh cua nhanh xuong va phan dudi cua nhanh len rat mong, goi la dean rnong cua- quai. Khi nhanh len cua quai Henle

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quay trd lai vung vo than thi thanh ong trd nen day nhu nhimg phan khac cua ong, do la dean day cua quai. Ong luon xa cling narn trong vung vo than, 'I'ai day, khoang 8 ong lucri xa h9P lai thanh ong gop vung vo. R5i ong gop rei vung vo di sau vao vung tuy than d~ trd thanh ong gop vung tuy. Sau do cac ong gop h9P lai thanh nhung ong gop len hon di suet qua vung tuy song song vdi quai Henle. Cac ong gop len d6 vao b~ than, Moi ong nay nhan nude ti~u cua khoang 4000 nephron.

Va5a recta

Hinli 6-1. Cdu. tao cua nephron

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1- NHlJNG NEPHRON VUNG VO VA VUNG C~N TUY

Cac nephron co cau than narn gan be mat cua than goi la nephron vung vo. Quai Henle cua chung chi di den phan ngoai cua tuy. Khoang 115 den 113 so nephron co cau than narn sau trong vung vo giap vung tuy than duoc goi la nephron canh tuy than. Cac nephron nay co quai Henle rat dai,

2- M~NG LVOI MAO M~CH QUANH ONG V A cAc MI\CH THANG

Chung quanh he thong ong than co mot mang mao mach rat phong phu goi la mang luoi mao mach quanh ong. Mau sau khi qua cau than se theo ti~u dong' mach di den mang luoi mao mach quanh ong. Hau het mang ludi mao mach 11&m trong vung vo than, quanh oug luon gan, ong lUQ11 xa va ong g6p vung vo. Ttl nhimg phan d sau cua mang hrdi nay, cac quai mach chia thanh nhanh dai goi la mach thang (vasa recta) di sau vao vung tuy, narn canh nhiing quai Henle, cho den tan gai than, Sau do chung quay trd lai vung vo va van chuyen mau vao tinh mach vung vo.

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3- CHUC NANG CVA NEPHRON

Chuc nang co ban cua nephron la 19c sach nhirng chat c6 hai hoac va Ich ra khoi huyet tuong khi mau chay qua than. L9C sach la clearance cling con dich la thanh thai. D6 la nhimg san pharn cuoi cung cua chuyen h6a nhu ure, creatinin, acid uric, urat, v.v. Nephron cling 19C sach luong ion thua ra khoi huyet tuong.

Khi mau qua cau than, khoang 1/5 luong huyet tuong duoc 19c qua cau than VaG ong than. Trong he thong ong, nhirng san pharn c6 hai khong nhfmg khong duoc tai hap thu, rna con duoc bai tiet tir huyet tuong qua te bao bieu mo rai VaG dich ong. Nguoc lai, nuoc, cac chat dien giai, cac chat chuyen h6a duoc tai hap thu VaG cac mao mach quanh orig.

4- LUU LUQNG MAu TH~N VA Ap SUAT TRONG TUAN HOAN TH~N

4.1- LUll LlfQNG MAu QUA TH~N

o mot nguoi nang 70 kg, luu luong mau qua ca hai than VaG khoang 1200 ml/phut; luu luong tim la 5600 ml/phut, nen phan so Icc cua than binh thuong la 21 %. C6 hai giuong mao mach g~n vdi nephron: giuong mao mach cau than, nhan mau tir ti~u d9ng mach den, rai mau theo ti~u d9ng mach ,di chay VaG giuong mao mach quanh ong than. Giuong mao mach cling- con goi la mang' ludi mao mach. Ap suat trong mao mach cau than cao (do ti~u dQng mach di c6 sue can IOn) lam cho dich duoc 19C lien tuc VaG bao Bowman. Ap suat trong mao mach quanh ong thap lam cho dich duoc tai hap thu lien tuc VaG cac mao mach. Chi c6 kho.uig 1 den 2% luu luong mau than chay qua cac mach thang. Vi viity rnau chay qua vung tuy than rat cham, trong khi d vung vo mau chay rat nhanh.

4.2- Ar SUAT TRONG TUAN HoAN TH~N

Ap suat trong cac dong' mach nho va ti~u dong mach den VaG khoang 100 mmHg, giarn xuong con 60 mm Hg trong mao mach cau than. Khi den mao mach quanh ong than, ap suat chi con 13 mm Hg.

QuA TRINH LOC a CAU TH~N

1- MANG CAU TH~N V A TINH THAM eVA MA~G

Mang cau than gam 3 ldp:

- Lop te bao noi mo cua mao mach

- Mang day

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- Lop te' bao bi~u rna phu tren mat ngoai cua mao mach.

Tuy c6 nhieu ldp nhung tfnh tharn cua mang cau than IOn hen mao mach cac noi khac tU 100 din 500 l~n, do cau true d<\ic biet cua n6 nhu sau (Hinh. 6-2)

Hinh 6-2. Cdu. true cluic nang eua truing cdu. tluin. - Lap te' bao n9i rna c6 hang ngan 16 nho goi la cac "cua s6".

- Mang day la mot mang ludi cac soi collagen va proteoglycan, ludi nay cling c6

nhirng khoang rQng cho phep dich 19C qua d~ dang.

- Lap te' bao bi~u rna khong lien tuc va c6 hang ngan, hang trieu nhirng ch6 15i ra hinh ng6n tay phu len mang day. Nhirng "ng6n tay" nay tao ra nhtrng khe hd d~ dich 19c qua.

Tinh tham cua mang ca.u than (duoc bi~u thi b&ng ti l~ cua n6ng dQ chat hoa tan trong dich 19C so voi n5ng dQ cua chat d6 trong huyet tuong) vdi cac chat c6 trong luong phan til khac nhau nhu sau:

Chat hoa tan

Trong hrong phan til (TLPT

Tfnh tharn

Inulin

Cac protein TLPT nho Albumin

5.200 30.000 69.000

1,0 0,5 0,005

Nhu vay mot chat c6 trong luong phan til bang' hoac nho hon 5.200 S8 duoc 19C qua mang cau than 100%; albumin chi qua duoc vdi ti l~ 0,5%.

Tinh tharn chon 19c cua mang phu thuoc VaG hai yeu to; kich thudc 16 19C va dien tich cua thanh 16 19C. Cac 16 19c c6 kich thudc du IOn d~ cho cac phan til c6 duong

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kinh 8 nm (80 A) di qua. Duong kinh cua ph an tli albumin la 6 nm, tai sao n6

kh6ng qua dU9C? Nguyen nhan la do cac khoang cua mang day dU9C lat bang phuc h9P proteoglycan tich dien (-) rat manh, Cac protein cua huyet tuong ciing tich dien (-) nen bi luc d~y tinh dien cua thanh 16 loc can lai,

2- THANH PHAN CllA D~CH LOC

Dich loc c6 thanh phan tuong W nhu cua huyet tuong, nhung c6 rat it protein (vao khoang 0,03% protein, nghia la bang 1124 protein trong huyet tuong). Do nong dQ protein mang dien tich (-) rat thap nen nong dQ cua nhiing anion kh6ng phai protein nhu Cl, HCO-3 trong dich loc cao hon trong huyet tuong khoang 5%.

3- LUU LUONG LOC CAU TH~N

Luu Iuong loc c§.u than la hrcng dich loc dU9C tao ra trong 1 phut d toan bQ nephron cua ca hai than. 0 ngiroi binh thirong, luu hrcng nay vao khoang 125 ml/phut. Nhu v~y toan bQ dich loc cau than m6i ngay vao khoang 180 lit, gap hon hai l§.n trong lucng co th~.

4- PHAN s6 LOC

D61a phan huyet tuong chay qua than duoc trd thanh dich loc. Binh thuong, hrong huyet tuong chay qua hai than la 650 ml/phut, luu hrcng loc cau than la 125 ml/phut. V~y phan so loc la 125/ 650 = 19% hoac 115.

5- CO CHE LOC QUA MANG CAU TH~N

Qua trinh loc d c§.u than chiu anh hucng cua nhung hrc sau:

- Ap suat thuy tinh cua mao mach cau than (PH), c6 tri so bang 60 mm Hg, c6 tac dung d~y dich vao bao Bowman.

- Ap suat thuy tinh cua bao Bowman (PB) vao khoang 18 mm Hg, c6 tac dung d~y dich vao mao mach, do do ngan can su loc.

- Ap suat keo cua mao mach cau than (PJ: ngan can su loc, c6 gia tri trung binh vao khoang 32 mmHg. 6 cau than khoang 1/5 hrong huyet tuong dU9C loc vao bao Bowman, nen nong d9 protein se tang len 20% khi mau di tit d§.u ti~u d9ng mach den tdi d§.u ti~u dong' mach di cua cau than. Ap suat keo d d§.u ti~u d(mg mach den la 28 mmHg thi ap suat keo d dau ti~u dong' mach di la 36 mmHg. Ta lay gia tri trung binh la 32 mmHg.

- Ap suat loc (PL) la ap suat c6 tac dung d~y dich loc qua mang c§.u than

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PL = PH - (Pn + Pr;)

= 60 - (18 + 32) mm Hg = 10 mm Hg.

6- HI~ SO LOC (Kr):

H~ so loc la ty l~ gifra luu hrong va ap suul loc

Kr=

125 ml/phut 10 mmHg

= 12,5 ml/plnit/mm Hg

7- cAc YI~U TO ANH HUONG DEN LUU LU()NG LOC

Tu cong tlnrc cua ap suat loc ta thay ba yeu to quyet dinh luu lucng loc la ap suat thuy tinh cua mao mach cau than, ap suat keo cua huyet tucng va ap suat thuy tinh trong bao Bowman. Tat ca nlnrng dieu kien nao anh hucng den ba yeu to tren cling se anh lnrcng den luu luong loc. D6 la:

7.1- ANH HVONG eVA LlfU LV<)NG MAu QUA TH!N

Luu luong mau qua than tang len se lam tang ap suat trong mao mach cau than va lam tang luu luong loc. Ngoai ra, con mot nguyen nhan nira: neu luu lucng mau qua than binh thuong thi khoang 20% huyet tuong duoc loc lam cho nong de_) protein huyet tuong cua mao mach cau than tang len, ap suat keo tang len se ngan can su loc, Khi luu luong mau qua than tang len, lucug huyet tucng den cau than tang len bu cho so huyet tuong da duoc loc, lam cho 116ng de_) protein va ap suat keo trong mao mach khoug tang len nhieu va tac dung ltc che su loc cua no se giarn di. Ket qua la ngay ca khi ap suat mao mach diu than khong d6i thi luu luong mau qua than cang tang, luu luong loc cang tang.

7.2- ANH HVONG CVA su eo TIEU DONG MACH Df~N

Co ti~u doug mach den lam giarn luong mau den than va cung lam giarn ap suat trong mao mach cau than. Ca hai tac dung nay deu lam giarn hru luong loc cau than.

7.3- ANH HVONG CVA su co TIEU DONG MACH DI

Co ti~u d9ng mach di can trd mau ra khoi mao mach cfru than do d6 lam tang ap suat mao mach cau than. Neu co nhe se lam tang luu hrong' loc. Neu ti~u d911g mach di co vua hoac co rat manh, huyst tuong bi giir lai d cau than trong mot thoi gian dai, luorig huyet tuong bi loc qua nhieu lion lam ap suat keo trong mao mach cau than tang cao, ket qua la luu lucng loc giarn du ap suat mao mach cau than

van tang.

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8- t)If~u HOA LUU LUQNG LOC CAU TH~N vA LUlJ LUQNG MAu TH~N

Luu lu'<!ng rna u den t han va lu'u Iuong 19c cfru t.h an luo:n du'9'c giu hang d in h n ho n hirng cd che d ieu hoa ngiroc t.ai ch6 d him trong th~n_ Co che tlj d ie.u h oa di~n ra nhu' sau:

8.1- Sl/TlJDIEU HOA LUlJ LV<)NG LOC CAU TH~N

Luu luong loc diu than phai hang' dinh vi neu luu luong loc giarn qua thap, dich di qua ang cham den muc hau nhu tat cD. cac chat deu dUQC tai hap thu va than khong dao thai dUQC cac san pharn co hai. Neu luu luong loc qua cao, dich qua ang nhanh den muc than khong co kha nang tai hap thu cac chat din thief cho co th~.

a nephron co hai co che dieu hoa nguoc: co che' lam gian ti~u dong mach den va co che lam co ti~u dong mach di. Su ket hop hai co che nay goi la dieu hoa nguoc ang than-cau than. Qua trinh dieu hoa x:ly ra tai phuc hop canh cau than (Hinh 6-3)

Hinh 6-3. Cdu. true cua phuc hap canh. cclu tluin.

Cau tao cua phuc hop canh diu than nhu sau: doan khoi dftu cua ang luon xa di VaG g6c giira ti~u dong mach den va ti~u dong mach di, va nhu vi;l.y n6 tiep giap voi ca hai ti~u dong mach nay. Cac te bao bieu mo cua ang lucri xa d ch6 tiep xuc voi cac ti~u dong mach thi darn dac hon cac te bao bieu mo ang khac va duoc goi la macula densa. Cac te bao macula densa bai tiet mdt so chat VaG ti~u dQng mach vi bQ may Golgi cua chung hudng ve cac ti~u dong mach chu khong hudng ve long ang nhu cac te bao bi~u mo ang d noi khac. a noi tiep xuc vdi macula densa, cac te bao

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co tron cua cac ti~u dong mach phong 1Em va chua nhirng hat sam mau. Do la cac te bao canh cau than va cac hat sam mau la nhirng phan tli renin d da-ig kh6ng hoat ·d9ng. Cac te bao cua ~acu1a dens a va cac te bao canh cau than diroc goi la phuc hop canh cau than. Dich trong ong luon xa dong vai tro quan trong trong viec kiem soat chuc nang cua nephron bang each cung cap nhung tin hieu dieu hoa nguoc cho ca. ti~u d9ng mach den va ti~u dong mach di.

* Cd che lam gian ti~u d<?ng mach den:

Khi luu Iucng 19C cau than giarn thap, su tai hap thu Na + va cr d quai Henle tang len, lam cho nang d(> cac ion nay d macula dens a giarn di, Cac te bao macula densa phat ra tin hieu lam gian ti~u dong' mach den, mau den cau than nhieu, ap suat mao mach cau than tang len lam cho Iuu lucng 19C d.u than tang trd lai mire binh thuong. Co che nay cung giup cho su dieu hoa luu luong mau than.

* Cd che co ti~u d<?ng mach di.

Su giam nang d(> Na + va cr d macula densa ciing lam cho cac te bao canh cau than giai ph6ng ra renin hoat dong. Renin xuc tac cho qua trmh tao angiotensin II. Angiotensin II lam co cac ti~u dong' mach di, Ket qua la ap suat mao mach cau than tang va luu luong 19C trd lai muc binh thuong.

Ca hai co che gian ti~u dong mach den va co ti~u dong mach di heat dong dang thoi lam cho luu Iuong 19C cau than duy tri d mire hang dinh, mac du huyet ap c6 th~ thay d6i tU 75 mm Hg den 160 mm Hg. Hai co che nay cling c6 tic dung digu hoa luu luong mau than.

8.2- ANH HlJONG CllA HUYlh Ap Lf~N LlJONG NlJOC TIEU - HmN TlJONG LOI TIEU DO HUYlh Ap

Cac gia tri cua huyet ap trung binh trong khoang tU 75 den 160 mm Hg chi i'mh hudng rat it den Iuu Iuong mau than va luu luong 19C cau than do co che' W dieu hoa da rna ta d tren. Nhung khi huyet ap tang hay giarn qua nhieu se lam tang hoac giam luu luong 19C cau than, trong khi qua trinh tai hap thu dich dang than lai it bi anh huong, ket qua Ib. luu luong nude ti~u cung tang hoac giarn theo. Vi du khi huyet ap trung binh giarn tU 100 mm Hg xuong 50 mm Hg, thi benh nhan se bi va nieu, Nguoc lai neu huyet ap trung binh tang gap d6i rnuc binh thuong (200 mm Hg) thi Iuong nude ti~u se tang gap 7 den 8 bin. Tac dung nay duoc goi la loi ti~u do huyet ap.

8.3- ANH HlJONG CllA KICH THICH GIAO CAM LEN LlJONG MAu DEN TH~N vA LlJU LlJONG LOC cAu TH~N.

Than kinh giao cam chi phoi ca ti~u dQng mach den, ti~u dQng mach di va mot phan ang than.

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Kich thfch nhe than kinh giao cam khong gay tac dung vi co che tv dieu hoa manh hon kfch thich than kinh.

Kich thfch rat manh than kinh giao cam lam co cac ti~u dong' mach than den n6i luu luongrnau than giam xucng muc b§.ng 10 den 30% gia trj binh thuong, va IUQng nude ti~u bang khong. Neu kfch thich manh tiep tuc duoc duy tri thi ca hru IUQng mau than, luu luong loc cau than va luu IUQng nude ti~u S8 trd vg rmrc binh thuong trong vong 20 den 30 phut. S,! khoi phuc cac luu IUQng mot phan do su giai ph6ng noradrenalin cua than kinh giao cam giarn di, mot phan do tac dung cua cac hormon, su dieu chinh cua cac ion va cac chat hoa tan trong than (xin xem phan tiep theo)

QuA TRINH TAl HAP THU vA BAI TIET 0 ONG TH~N

Dich loc cau than S8 Ian IUQt chay qua ong IUQn gan, quai Henle, ang IUQn xa, ong g6p vung vo, ang g6p, r6i VaG b~ than. Trong qua trinh chay qua ang than, cac chat duoc tai hap thu hoac bai tiet mot each chon 19C bdi cac te bao bi~u rna, va dich trd thanh nude ti~u. S,! tai hap thu dong vai tro quan trong hon su bai tiet trong qua trinh tao nuoc ti~u. nhung su bai tiet lai dac biet quan trong trong viec xac dinh so hrong cac ion K+, H+ va mot so chat khac trong nude ti~u.

1. KHA NANG TAl nAp THU eVA cAe DOAN KHAe NHAU eVA ONG THAN

. .

eau tao cac dean cua ong than d (Hinh 6·4)

:f}U-?1? /TlQ/7_9 fjuai Henle

Hinli 6-4. Diic trung cua te' bao bilu mo d cdc doari hluic nhau cua ong tluiri

1.1. TE BAo BIE:U MO ONG LVQN GAN

Te bao bi~u rna ang IUQn gan la nhirng te bao c6 kha nang chuyen h6a cao; chung chua nhieu ti lap th~ d~ cung cap nang IUQng cho cac qua trinh van chuyen

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tieh cue, Khoang 65% dich loc cau than duoc tai hap thu dong luon gan. 0 diem ban chai cua te' bao bieu mo ong hron gan e6 nhieu protein mang, giup eho su tai hap thu hoac bai tiet cac chat theo cd che van chuyen tich cue thu phat cung chieu hoac nguoc chien.

Cac te' bao bi~u mo noi vdi nhau bang nhirng moi noi khit d phia long ong. Giira hai te' bao e6 mot khoang ke. Rat nhieu ion Na + duoc born tU te bao VaG cac khoang ke nay.

1.2. TE BAO J)O~N MONG eVA QUAI HENLE

o dean nay, te' bao bi~u mo det, khong e6 diem ban chai va rat it ti lap th~.

Phan xuong ella dean mong e6 tinh tham eao vdi nude, tharn vua phai vdi Naf• ure va cac ion khac. Phan len ella dean mong khong tharn nude. SV khac nhau nay rat quan trong trong cd che co d~e nude ti~u.

1.3. TE BAo BlEU MO eVA J)O~N DAY NHANH LEN eVA QUAI HENLE

Cac te bao nay gi6ng te bao 6ng hiqn g~n. Chung dac biet thieh hop eho qua trinh van chuyen tich cue ella ion Na+ va cr tU long ong VaG dich ke. Dean day khong tham nude va ure. Doan nay dong vai tro quan trong trong cd che pha loang nude ti~u.

1.4. TE BAO 6NG LVQN XA

6ng luon xa duoc chi a thanh hai dean la dean pha loang va dean cuoi.

- Cac te' bao ella doan pha loang e6 cau true giong ella doan day quai Henle.

Chung eho hau het cac ion di qua, nhung lai khong tham nude va ure. Doan nay

? ,

cung e6 chuc nang pha loang nude tieu.

- Cac te' bao doan cuoi ong luon xa va ong g6p vung va e6 nhirng dac tinh sau: + Chung hOa11 toan khong tham ure

+ T'ai hap thu Na I va bai tiet K+ dudi su ki~m soat ella aldosteron.

+ Cac "te bao nau" ella doan cuo] ong luon xa va ong g6p vung vo bai tiet ion H+ theo cd ehe van chuyen tieh cue nguyen phat. Cac te bao nay d6ng vai tro quan trong trong viec xac dinh pH nude ti~u.

+ Cac te bao eho nude tham qua khi e6 mat hormon ADH va khong tham nude khi hormon nay vang' mat.

1.5. TE BAo ONG G6p

Te bao ong g6p e6 hai d~e tinh:

- Tfnh tham nude ella te bao phu thuoc VaG nong dQ ADH trong mau. Khi n6ng d9 ADH tang eao, nude dU<;1C tai hap thu nhieu VaG dich ke vung tuy va th~ tich nucc ti~u giarn, nude ti~u bi co d~c.

12

- Te bao ong g6p cung c6 kha nang bai tiet H+ theo co che' tich cue nguyen phat, do do g6p phan ki@m so at can bang toan kiern cua cac dich co th~.

2. cAC CO CHE V ~N CHUYEN QUA MANG ONG TH~N

(j ang luon, cac chat duoc tai hap thu va bai tiet theo nhtrng co che sau:

- V~n chuyen tich eire nguyen phat vi du born Na +, Ir- - A'I'Pase.bom H +. - ATPase.

- V~n chuyen tich cue thu phat, cling chieu, vi du su tai hap thu glucose, acid

amir. dang hron g§.n cling voi Na + .

- Van chuyen tich cue thu phat nguoc chieu, Vi du: su bai tiet H+, K+ vao long ang, nguoc chieu voi ion Na +.

- Kh uech tan don th uan

- Khuech tan thuan h6a (facilitated diffusion).

3. SV TAl HAP THU V A BAI TIET cAc CHAT 0 ONG LU(JN GAN

3.1. SlJTAI HAP THU ION Na'

- Born Na +, K+ - ATPase khu trii d mat ben va mat day te bao bieu rna, c6 tac dung born Na + tU te bao ra dich ke va born K+ tu dich ke vao te bao, Nhung cac mat day-ben cua te bao bi~u rna c6 tinh tham cao dai voi ion K+ (gap 50 den 100 l§.n so voi ion Na +) nen gan nhu tat ca ion K+ sau khi duoc born vao ben trong te bao lai lap tuc khuech tall trd lai dich ke theo bac thang nong dQ. Nhu vay tac dung thuc cua born Na + K+ chi la born rat nhieu ion Na + ra dich ke lam cho n6ng d9 ion Na + d trong te bao rat thap.

- Mang te bao bi~u rna phfa long ang ducc vien bang diem ban chai lam cho dien tich tiep xuc cua mang ang tang len 20 Ian. Trong diem ban chai c6 rat nhieu protein mang tham gia van co che van chuyen tich cue thu phat dang luon g§.n. D6 la:

- Su dong van chuyen vdi Na + cua glucose hoac cac acid amin tU long ang van trong te bao bieu ma~ d long orig, cac protein mang giin d6ng thoi vdi ca glucose (hoac acid amin) va Na +. Do su chenh lech nong d9 cua ion Na + rat len tU long ang van te bao nen Na + van dong' thea bac thang dien h6a van ben trong te bao, keo theo glucose (hoac acid amin) di cling vdi n6. M6i loai protein mang dac hieu voi su van chuyen cua mot chat hoac mot loai chat.

- Su bai tiet tfch cue cua H+ nguoc chieu vdi ion Na +: d ben trong te bao bi~u rna, ion H+ giin vdi protein mang trong diem ban chai, trong khi ion Na + trong long ang g&n vdi dau kia cua cling mot protein mango Khi Na + van chuyen van ben trong theo bac thang dien h6a, thi ion H+ bi d:[y ra long ang.

Khoang 65% ion Na + diroc tai hap thu dang luon gan.

T2 - SLH

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3.2. s1/TAI HAP THU ION cr

Ion cr duoc khuech tim thu dong theo ion Na + d~ duy tri su trung hoa dien.

3.3. S1/ TAl HAP THU ION K+

6 ong luon g::in ion K+ duoc tai hap thu theo co che d6ng van chuyen voi ion Na'.

3.4. S1)' TAl HAP THU ION HCO ·3

Ion HC03" duoc tai hap thu mot each gian tiep qua CO2 nhu sau: 6 ben trong te bao bieu mo, CO2 duoc sinh ra trong qua trinh chuyen h6a se ket hop vdi nuoc voi su xiic tac cua men carbonic anhydrase (C.A) d~ tao ra HzCO;j: H2C03 phau ly thanh ion H+ va ion HC03"; ion H+ duoc bai tiet tich C\lC VaG long ang. Tai day ion HI ket hop voi ion HC03" c6 trong dich ang d~ tao thanh H2C03; H2C03 se phan ly thanh CO2 va H20; nude d lai dich ang, con CO2 khuech tim VaG trong te bao. 6 trong te bao CO2 se ket hop vdi nude (co su xiic tac cua men C.A) thanh H2CO;~; H2CO;3 phan ly thanh ion H+ va ion HC03"; ion HI duoc bai tiet VaG long ang con ion HC03" khuech tan VaG dich ke.

Dich ke Te bao bi~u mo ang than Long ang
HC03 •....... ... HC03" H+ H+ HC03"
-, / \ I
H2C03
i CA
t HZCO:1
H2O I \
+
CO2 ............ ......... CO2 + H2O
i
Chuyen h6a te bao 3.5. TAl HAP THU URE

Ure cung duoc tai hap thu theo co che thu dong nhung vdi mire dQ it hon cr vi muc dich chu yeu cua than khong phai la tai hap thu ure rna la lam sao cho san pham chuyen hoa co hai nay duoc bai tiet VaG nude ti~u cang nhieu cang tot. Tuy nhien vi phau tl'i ure co kich thudc rat nho, ang than cho ure tham qua mot phan, nen khi nude duoc tai hap thu tu ang than thi khoang mot mra luong ure co trong dich IQc cau than se duoc tai hap thu thu dong cung voi mroc, mot mra con lai bai xuat theo nude ti~u.

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3.6. TAl HAP THU NV6c

NUDC duoc tai hap thu thu dong theo Na + va cr theo luc tharn thau. Khi Na + va cr duoc van chuyen VaG khoang ke te bao, chung se tao ra mot hrc tharn thau hut nUDC tir long ong qua cac moi noi khit giiia cac te bao bi~u m6 d~ VaG khoang ke r6i VaG mau, Khoang 65% nude duoc tai hap thu dong hron gan. Dich ra khoi ong luon gan la dich d<1ng truong.

3.7. st)'TAI HAPTHU cAe CHAT DINH DU'ONG

Glucose, protein, acid amin, ion acetoacetat va cac vitamin, cac chat nay c6 trong dich 19C cau than la nhimg chat dinh dudng quan trong cua co th~. Binh thuong cac chat nay duoc tai hap thu hoan tcan dong luon gan theo co che' van chuyen tich cue, Trude khi dich di khoi ong hron gan, ndng dQ glucose, protein, acid amin trong dich da giarn xuong bang kh6ng.

- Su tai hap thu protein: m6i ngay c6 khoang 30 gam protein duoc 19C VaG cau than.

Vi phan tli protein qua IOn nen protein diroc tai hap thu qua diem ban chai cua te bao bi~u m6 ong hron gan theo co che &m bao. 6 ben trong te bao, protein duoc tieu h6a thanh cac acid amin r6i cac acid amin duoc khuech tan qua mang day va mang ben VaG dich ke theo co che khuech tan c6 chat mango

- Su tai hap thu glucose: d diem ban chili, glucose duoc van chuyen tich cue thu phat, Khi nong dQ glucose tang cao trong te bao, glucose duoc khuech tan qua mang day ben VaG dich ke theo co che khuech tan co chat mang (facilitated diffusion).

3.8. st)' TAl HAP THU cAc sAN PHAM CHUYEN H'OA CUDI CUNG (lJRt, CREATININ vA cAc CHAT)

Chi mot luong nho ure duoc tai hap thu d ong than trong khi tren 99% nude duoc tai hap thu, lam cho ure duoc c6 d~c khoang 65 Ian.

Creatinin kh6ng nhirng kh6ng duoc tai hap thu rna mot luong nho creatinin con duoc bai tiet dong hron gan, do d6 nong' dQ creatinin tang len 140 Ian.

Ion urat tuy duoc tai hap thu nhieu hen ure, nhung van c6 mot luong IOn urat duoc bai xuat ra nude ti~u. Sulphat, phosphat. nitrat duoc tai hap thu tuong tu nhu urat. Cac chat nay duoc tai hap thu tich cue trong mot chung muc nhat dinh d~ cho nong dQ cua chung trong dich ngoai bao kh6ng giarn xuong qua thap.

3.9. str HAl TIth ION W

Ion H+ duoc bai tiet theo co che van chuyen tich cue thu phat nguoc chieu vdi ion Na + (xem di~m 3.1. Tai hap thu natri).

15

4. SV TA.l HAP THU 0 QUAI HENLE

Nhanh xuong cua quai Henle cho nude tham qua, nhung rat it tharn cac ion.

Nhanh len khong tham nuoc va ure va thich hop cho co che' van chuyen tfch cue cua Na +. Qua trinh tai hap thu nude va cac ion d quai Henle dien ra nhu sau: d nhanh len, ion Na j duoc van chuyen tich cue tU long ong VaG dich ke, cong them su d6ng van chuyen cua ion Cl, K+ va mdt so ion khac VaG dich ke lam cho nong dQ cac ion tang dan trong dich ke vung tuy ugoai. a nhanh xuong, do su chenh lech ap suat tharn thau giira long ong va dich ke va cling do tinh tharn cao cua doan nay doi voi nude, nude se khuech tan VaG dich ke lam cho nong dQ ion d trong ong tang cao dan va tang cao nhat d chop quai, tao dieu kien thuan lei cho su van chuyen tich cue cua cac ion d nhanh len. Khoang 27% ion Na +, K+ va cr trong dich loc cau than duoc tai hap thu d doan day nhanh len cua quai Henle trong khi chi co 15% nude duoc tai hap thu, nen dich orig di VaG ong hron xa la dich nhuoc truong.

5.81)' TAl HAP THU vA BAI TIET dONG LU'<;jN XA

5.1- SlfTAI HAP THU 0 D01\N PHA LOANG

Dean pha loang la mra dau cua ong luon xa va co cung dac tinh nhu dean day cua nhanh len quai Henle. Tai day ion duoc tai hap thu, nhung mang ong khong tharn nude va ure, do do doan nay cling gop phan pha loang dich orig.

5.2- SlfTAI HAP THU vA BAI TIET 0 DOA.N eUDI eVA DNG LVQN XA vA DNG GOP VUNG VO

t

Tai day nude va cac ion duoc tai hap thu va bai tiet nhu sau:

8l! tai hap thu Na ",

Toc dQ tai hap thu Na + duoc ki~m soat boi nong dQ aldosteron trong mau. Neu nong dQ aldosteron rat cao, Na + se duoc tai hap thu het va khong co Na + trong nude ti~u. Nguoc lai, neu khong co aldosteron, hau het Na + di vao doan cuo] cua ong hron xa (vao khoang 800 mEq/ngay) se khong duoc tai hap thu va di VaG nude ti~u. Nhu v;%ty su bai xuat Na + co th~ thay d6i tu rat it den rat nhieu (tir O,lg den 20g/ ngay) tuy theo nong dQ cua aldosteron trong rna u.

Co che tac dung cua aldosteron: Aldosteron g<ln vdi mot protein receptor trong bao tuong cua te bao bi~u rna d~ tao thanh phuc hop aldosteron-receptor. Phuc hop nay khuech tan VaG nhan, hoat hoa cac phan tv ADN d~ tao ra mot hoac nhieu loai ARN thong tin. Cac ARN thong tin giup tao ra cac protein enzym can cho qua trinh van chuyen Na +. Thong thuong phai 45 phut sau khi dua aldosteron VaG cd th~ thi cac protein dac hieu cho qua trinh van chuyen Na + mdi xuat hien trong cac te bao bieu rna, r6i qua trinh van chuyen Na + se tang dan trong vai gid tiep theo.

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·Slj hili tiet K+.

o doan CUQi cua Qng luon xa va Qng gop vung vo co nhimg te bao goi Ia te bao chinh, chiern khoang 90% te bao bi~u mo d hai doan nay. Cac te bao chinh co kha nang bai tiet mot lucng rat Ion ion K+ vao long Qng khi nong d9 K+ trong dich ngoai bao cao hon binh thuong. Co che bai tiet K+ nhu sau (Hinh 6-5) .

• Nit

I I

-- ---_./

Hinh 6-5. Co che'v(in chuye'n Na + va K qua ti bao bie'u mo {Ing luati xa

o mang day - ben cua te bao chinh, born Na+, K+ - ATPase hoat d9ng born Na+ tU te bao vao dich ke, d6ng thoi born K+ vao ben trong te bao. Mang Qng cua cac te bao chinh rat tham K+, do do khi ndng dQ K+ tang cao trong te bao thi K+ se nhanh chong khuech tan vao long Qng. Nhu vay su bai tiet K+ phu thuoc chu yeu vao born Na + -K+ d mang day.ben. D~ cho born nay hoat dong, ~on Na + phai diroc khuech tan lien tuc tu long Qng vao te bao, d~ r6i duoc trao d6i vdi K+ d mang day ben. Vi vay sO' lucng ion Na + khuech tan tU long Qng vao te bao cang nhieu thi so lucng K+ bai tiet cang tang. Neu mot nguoi phai an nhat keo dai thuong khong c6 kha nang bai xuat K+ mot each binh thuong nen co th~ bi tang kali huyet.

SV bai tiet ion K+ cling chiu su dieu hoa cua hormon aldosteron vi a1dosteron heat hoa born Na ', K+ - ATPase.

• Slj hili tiet ion H+.

o doan CUQi Qng luon xa, Qng g6p vung vo va Qng gop ciing co mot loai te bao d:;ic

. biet goi la te bao xen ke (hoac te bao nau). Cac te bao nay co kha nang bai tiet ion H+ theo cd che. van chuyen tich cue nguyen phat. D:;ic tinh cua qua trinh van chuyen nay hoan toan khac vdi h~ thong van chuyen tich cue thu phat d nhirng phan d<lu cua Qng than: no chi chiern duoi 5% t6ng sO' ion H+ duoc bai tiet, nhung no bai tiet ion H+ nguoc lai bac thang nong d9 cao gap 900 l<ln nong d9 trong te bao, trong khi d Qng luon g<ln chi la 3-4 Ian va d doan dfru Qng luon xa la 10 den 15 Ian. Ion H+ duoc co dac d doan CUQi cua Qng luon xa va Qng gop 900 Ian nhu v~y se

17

lam cho pH cua dich 6ng giarn xu6ng can 4,5 la gioi han thap nhat cua pH nude ti~u (Hinh 6-6).

Hinh 6-6. Slj v(in ehuye'n tieh cue nguyen pluit

eua ion tr qua mang ang - eua ti bao bie'u mo

Co che van chuyen tfch cue nguyen phat cua ion H+ xay ra d mang 6ng cua te bao bi~u mo nho mot protein mang dcrtc hieu goi la "protein mang H+ - ATPase"

• Sl;f tai hap thu nude.

o dean cu6i cua 6ng luon xa va 6ng g6p, su tai hap thu nude phu thuoc vao n6ng d(> ADH cua huyet tuong. ADH lam tang tai hap thu nude d 6ng lucri xa va 6ng g6p theo co che sau: tai mang day - ben cua te bao bi~u mo, ADH hoat h6a men adenylcyclase. Men nay xuc tac cho phan ung bien ATP thanh AMP yang trong bao tucng, AMP yang khuech tan vg phia mang 6ng cull' te bao. Tai day AMP yang lam cho nhfrng cau true hinh tui dai trong bao tuong phat tri~fl va hoa mang vdi mang 6ng cua te bao. Mang cua nhfmg tui nay trd thanh mot phan cua mung 6ng, nhu nhirng "mieng va" tren mango Nhiing mieng va nay chua nhieu protein c6 nhimg kenh d~n nude rat rong lam cho mang 6ng binh thuong hau nhu khong tharn nude, nay trd nen ren tharn nude. Khi khong c6 mat ADH, cac cau true hinh tui tach khoi mang 6ng va trd lai vi trf ben trong bao tuong trong yang 15 den 20 phut. Cac te bao 6ng lai trd nen khong tham nude. Khoang 10% nude cua dich 19C cau than duoc tai hap thu d 6ng luon xa.

6. su TAl HAP THU vA BAI TIET 0 ONG GOP.

o 6ng g6p, su tai hap thu nude cling phu thuoc vao nong' d(> ADH huyet tucng.

Khi ndng d(> ADH huyet tuong cao, nude duoc tai hap thu vao dich ke vung tuy lam cho th~ tich nude ti~u giarn, va lam co dcrtc hau het cac chat hoa tan trong nude ti~u. Khoang tren 9% nude cua dich loc cau than ducc tai hap thu d 6ng g6p.

18

Te' bao bi~u rna 6ng g6p ciing cho tham qua mot it ure do do mot lucng ure duoc tai hap thu vao dich ke vung tuy. Tuy nhien, hau he't lucng ure nay duoc khuech tan trd lai VaG quai Henle, qua 6ng luon xa, rai mot Ian nfia lai xuong 6ng g6p d~ duoc bai xuat theo nude ti~u.

Te' bao bi~u rna 6ng g6p c6 kha nang bai tie't ion H+ theo co che' van chuyen tich cue nguyen phat nhu d doan cu6i 6ng luon xa va 6ng g6p vung vo. Vi v~y 6ng luon xa va 6ng g6p c6 vai tro quan trong trong viec digu hoa can b:1ng toan kiern cua co th~.

7. KET QuA TAl HAP THU V A BAl TlET 0 6NG THJ.N

Khi dich loc cau than di VaG 6ng than, cac chat dinh dudng duoc tai hap thu hoan toan d 6ng lucri gan, neu nang d9 cua cluing d huyet tuong narn trong gidi han binh thuong. Ion Na + duoc tai hap thu 65% d 6ng luon gan; 27% d doan day nhanh len quai Henle; 8% ion Na + duoc tai hap thu d 6ng luon xa duoi tac dung digu hoa cua aldosteron. Ion cr duoc tai hap thu theo Na + hoac theo co che. khuech tan hoac theo co che d6ng van chuysn vdi Na +. Ion K+ duoc tai hap thu 65% d 6ng lucri gan; 27% d doan day cua nhanh len quai Henle; 8% ion K+ can lai di vao 6ng luon xa, tire la vao khoang 65 rnEq rn6i ngay trong khi mot nguoi binh thucng mot ngay an VaG khoang 100 rnEq ion K+. Do do khi nang d9 ion K+ trong dich ngoai bao binh thuong hoac tang len thi mdt lucng IOn K+ can phai duoc bai xuat VaG nude ti~u d~ dua phan K+ thua ra rn6i ngay ra khoi co th~. Vi v~y cac te' bao dean cu6i cua 6ng luon xa phai bai tie't K+ VaG long 6ng. Su tai hap thu ion HCO; duoc thuc hien gian tiep qua CO2. a 6ng lucri gan, trong nhirng digu kien binh thuong, t6c d9 19C cua ion HCO; trong dich 19C cau than la 3,46 rnrnoll phut va t6c d9 bai tiet ion H+ d te' bao bi~u rna 6ng lucn gan 10. 3,5 mmol/phiit. Nhu vay so hrcng hai loai ion nay trong dich 6ng la bang nhau. Chung ket hop vci nhau va san pharn cu6i cling 10. CO2 va nude; CO2 khuech tan VaG te' bao, ke't hop voi nude d~ thanh H2C03. H2C03 phan ly thanh H+ va HC03, H+ lai duoc bai tie't can HC03 duoc khuech tan VaG dich ke. Nhu v~y cli mot ion H1- duoc bai tiet thi mot ion HC03 duoc tai hap thu d 6ng luon gan d~ gift cho pH cua dich ngoai bao duoc hang dinh, Hai san pharn cuci cling cua chuyen h6a la ure va creatinin rat it duoc tai hap thu, do do nong' d9 ure trong nude ti~u cao gap 65 Ian nang dQ ure trong huye] tuong, Creatinin khong nhimg khong duoc tai hap thu rna can duoc te' bao bi~u rna 6ng lucri gan bai tie't vao dich 6ng nen ndng di) cua creatinin trong nuoc ti~u tang gap 140 Ian. Cac ion CaH-, Mg++, urat, phosphat, sulphat, nitrat dgu duoc tai hap thu theo co che' van chuyen tich cue chu ye'u d 6ng luon gan. Cac te' bao bi~u rna cua 6ng luon gan, doan day cua nhanh len quai Henle va 6ng lucn xa dgu c6 kha nang bai tie't ion H+ VaG dich 6ng theo co che van chuyen tich cue thu phat (van chuyen

19

nguoc chieu vdi ion Na +) vdi mot so luong rat Ion - vao khoang vai ngan mEq moi ngay. Rieng d doan cuoi cua ong luon xa va cac ong gop, te' bao bi~u rna bai tie't ion H+ vao dich ong theo co che van chuyen tfch cue nguyen phat.

8. T AC Dl)NG CVA KHA NANG TAl Y A KHA NANG Y ~N CHUYEN TOI DA 'I'm (Transit maxima) CVA ONG TH~N DOl vor THANH PHAN NUde TIEU

8.1. KHA NANG TAl CVA 6NG (TUBULAR LOAD)

Kha nang tai cua ong doi vdi mot chat la luong chat do duoc 19C qua mang cau than vao ong than moi phut. Vi du, moi phut co 125 ml dich 19C qua cau than, nong dQ glucose trong mau la 100mg/100ml thi kha nang tai cua ong than doi vdi glucose

1, 100mgx125 125 / hti T t h ~ khs v tai ci' ~, tha ,.

a 100 = mg put. uong V n U V?y a nang ai cua ong an voi

Na + la 18 mEq/ phut; cua ion cr la 13 mEq/ phut.

8.2. KHA NANG V ~N CHUYEN T6I DA CVA 6NG TH~N D6I V6I MQT CHAT

Moi chat dUQC hap thu hoac bai tie't tich cue can phai co mot he thong van chuyen dac hieu khu tru trong cac te' bao bi~u rna ong than. LUQng toi da rna chat do co:th~ duoc tai hap thu hoac bai tiet phu thuoc vao toc dQ hoat dong toi da cua he thong van chuyen, nghia la phu thuoc van luong chat mang va cac enzyrn dac hieu. Nhu V?y moi chat dUQC tai hap thu tich cue deu co mot toc dQ tai hap thu toi da rieng cua chat do, va duoc goi la kha nang van chuyen toi da cua ong than doi voi chat do (Trn). Vi du T m cua glucose la 320 rng/phut, neu kha nang tai cua ong than doi vdi glucose IOn hon 320 mg/phut thi luong glucose thua ra se di vao nude ti~u. Binh thuong kha nang tai cua ong than voi glucose la 125 mg/phiit, nen tat ca glucose deu duoc tai hap thu. Ne'u nong dQ glucose trong mau tang len de'.n 180 mg/ 100 ml, kha nang tai cua ong than doi voi glucose la 220 mg/phut, thi glucose bAt dau xuat hien trong nude ti~u. Neu kha nang tai cua ong than voi glucose tang den 400 mg/phut thi luong glucose bi mat theo nude ti~u se bang kha nang tai cua ong tru di Tm cua glucose, tire la bang 400 rng/phut - 320 rng/phut = 80 mg/phut.

8.3. NGU'ONG CVA TH~N D6I V6I NHUNG CHAT CO Tm

Khi mot chat co Tm thi chat do cung co mot nong dQ ngudng trong huyet tuong, nghia la neu nong dQ chat do trong huyet tuong thap hen ngudng thi chat do khong co trong nude ti~u. Neu cao hon, chat do se xuat hien trong nude ti~u. Vi du khi nong dQ glucose trong mau la 180 mg/ 100 ml thi kha nang tai cua ong doi vdi glucose la 220 mg/phut va glucose bat dau xuat hien trong nude ti~u. Nhu vay 180 mg/ 100 ml la ngudng than doi voi glucose.

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Bang 6-1 - T m cua m9t so chat dUQC tai hap thu d ong than.

Chat dUQC tai hap thu T m (mg/phut) Chat dUQC tai hap thu Tm (mlvl/phiit)
glucose 320
protein 30 acid arnin 1,5
hemoglobin 1 phosphat 0,1
lactat 75 sulphat 0,06
urat 15
acetoacetat 30 8.4. str TAl HAP THU CVA NHi1NG CHAT KHONG CO Tm

81,1' hap thu cua cac chat theo cd ehe' khuech tan phu thuoc vao hai yeu to:

- Bac thang n6ng dQ qua mang cua chat do, bac thang nay khong co bat ky mot gioi han toi da nao.

- Thoi gian dich chua chat nay duoc luu gift trong long ong. Vi v~y s1,1' van chuyen cua cac chat theo co che' khuech tan duoc goi la s1,1' van chuyeri bac thang - thoi gian (gradient-time transport).

Na + la mQt chat duoc tai hap thu nhanh theo cd che. van chuyen tieh cue nhung lai khong co trong danh sach cac chat co Tm bdi vi ben canh yeu to toc dQ toi da cua qua trinh van chuyen tich cue, con co nhiing yeu to khac gidi han toc d9 van chuyen cua Na+. Do la: trong ong hron g§.n, toc dQ van chuyen tich cue cua Na LU te bao qua mang day - ben vao dich ke ldn hon rat nhieu so vdl toe dQ khuech tim thu dQng cua Na + tU long ong qua diem ban chai vao te' bao. Nhu v~y toc dQ toi da cua cd che' van chuyen tich cue khong th~ la ye'u to gioi han quyet dinh t6c de? tai hap thu Na 1. Ngoai ra con co met yeu to khac ciing gioi han s1,1' hap thu Na +. Do la s1,1' khuech tan nguoc trd lai cua nhieu ion Na + tU dich ke qua cac moi noi gift a cac te bao bi~u rna d~ vao long ong. Vi nhiing ly do tren, s1,1' van chuyen cua Na ~ dong luon gan chu ye'u tuan theo nguyen ly cua s1,1' van chuyen bac thang-thoi gian, hon la kha nang van chuyen toi da. Nghia la, n6ng dQ Na + trong ong luon gan cang ldn, thoi gian dich duoc gift trong ong luon gan cang lau, thi s1,1' tai hap thu cua Na + cang nhieu.

A ?

V cac doan xa cua ong than, cac moi noi giira cac te bao bieu rna khit chat hon,

nong dQ Na + trong long ong thap hon, nen s1,1' van chuyen cua Na~ lai c6 Trn giong nhu cac chat duoc tai hap thu tich cue khac. Hen niia Trn doi vdi Na + con phu thucc vao nong d(_) cua cac hormon aldosteron va angiotensin II d~ kiern soat toe d(_) bai xuat Na ~ vao nude ti~u.

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8.5. CAN BANG CAU TH~N.6NG TH~N TRONG 6NG LU'QN GAN

Khi nghien cuu ve su tai hap thu cua ion Na + va cua nude trong ong lucri gftn, nguoi ta phat hien ra mot tac dung d(lc biet quan trong goi la "can bang cau thanong than". Nghia 10. trong nhirng dieu kien binh thuong, khi dich 19C di qua ang luon gan, khoang 65% ion Na + va nude se duoc tai hap thu, Ti l~ % nay la hang' dinh cho du Iuu lucng 19C cau than c6 thay d6i. Vi du, khi hru lucng 19c cau than 10. 100 ml/phut, thi tai hap thu dong lucn gan la 65 ml/phut; khi luu luong 19C cau than tang den 200 ml/phut, hru hrcng tai hap thu dong luon gan cung tang gap doi, nghia 10. bang 130 ml/plnit d~ duy trl slJ can bang theo tll~ khoang 65% dich 19c ca u than.

SlJ can bang cau than-eng than c6 tac dung ngan ugua tinh trang qua tiii ella cac phan sau cua ang than m6i khi luu hrcng 19C cau than tang len. Ngoai ra co che dieu hoa nguoc d~ ki~m soat luu hrong 19C cau than cung c6 vai tro quan trong trong viec ngan cho cac phan sau ella ong than khoi bi qua tai. Ket qua la cac h~ thong dieu hoa dong than nham ki~m soat nong d9 cac chat bai xuat thea nuoc ti~u heat d9ng mdt each hiru hieu.

KHAI NI~M CLEARANCE HUY~T TU'dNG vA U'NG Dl)NG DE DANH GIA CHUC NANG TH~N

1. D~NH NGHIA

Clearance huyet tuong cua mot chat la kha nang than c6 th~ 19C sach chat do khoi huyet tuong trong thci gian mot phut.

Vi du: N6ng d9 cua ure trong met ml huyet tuong va dich loc cau than la 0,26 mg; Iuong ure di vao nude ti~u trong 1 phut la 18,2 mg. Ta c6 th~ tinh duoc so millilit huyet tuong duoc 19C sach ure trong 1 phut bang each chia luong ure di VaG

nude ti~u trong 1 phut cho hrong ure c6 trong mot ml huyet tuong: 18,2 = 70

0,26

ml/plnit, Nhu vay clearance huyet tuong cua ure la 70 ml/phut.

Clearance huyet tuong cua met chat dUQC tinh theo cong thuc sau:

Clearance

huyet tuong _ Iltu lUQng nuoc ti~u (ml/ph) x n6ng dQ trong nuoc ti~u(mg/ml)

(ml/ph)

N6ng d9 trong huyet tuong (mg/ml) ,

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2. SU DUNG CLEARANCE HUYET TVONG DE DANH GIA CHU'C NANG TH~N 2.1. DUNG CLEARANCE INULIN D~ DO LUlJ LVONG LOC CAU TH~N

Inulin la mot polysaccarid c6 trong hrcng phan tv 5200 nen c6 th~ duoc loc d~ dang qua mang cau than, nhung n6 khong duoc tai hap thu va bai tiet d ang than. Ket qua la nang d9 inulin trong dich loc cau than va trong huyet tuong gidng nhau. Khi dich loc chay xuong ang than, tat ca inulin duoc loc se c6 mat trong nude ti~u. N6i mdt each khac tat ca dich loc cau than deu duoc loc sach inulin hoac clearance huyet tuong cua inulin bang luu luong loc cau than.

Vi du: Ket qua xet nghiern cho biet nang d9 inulin huyet tuong la 1 mg/ml va c6 125 mg inulin di vao nude ti~u trong 1 phut, Clearance huyet tuong cua inulin la

bang' 1~5 = 125 ml/phut, nghia la d~ nude ti~u c6 nang d9 inulin nhu tren thi phai c6 125 ml dich lee duoc tao thanh trong mot phut, Nhu vay luu luong loc cau than la 125 ml/phut,

Nguoi ta ciing c6 th~ dung mannitol hcac iothalamat ph6ng xa thay cho inulin d~ do luu luong loc cau than.

2.2. DUNG CLEARANCE HUYET TVONG CVA PAH D~ DO LUlJ LVONG HUYET TVONG QUA TH~N

PAH ( acid paraaminohippuric) qua mang cau than rat d~ dang. Nhung hau het PAH con lai trong huyet tuong sau khi dich loc cau than duoc t'.1O thanh se duoc bai tiet tu mao mach quanh ang vao te' bao bi~u rna ang luon geln, roi tu te' bao vao long ang. Chi c6 khoang 1/10 lucng PAH ban dau con lai trong huyet tuong hie mau rei khoi than.

NgUdi ta c6 th~ dung clearance cua PAH d~ tinh luu luong mau qua than. Gia sv c6 0,01 mg PAH trong 1ml huyet tuong; c6 5,85 mg PAH vao nude ti~u trong 1 phut, ta c6 585 ml huye't tuong duoc loc sach PAH trong 1 phut. Ne'u mot lucng huyet tuong nhieu nhu v~y duoc lee sach PAH trong 1 phut thi it nhat luong huyet tuong nay phai di qua than trong cung thoi gian d6. Vi hau nhu to an b9 PAH duoc loc khoi huyet tuong khi mau qua than nen 585 ml chinh la hrcng huyet tuong chay qua than trong mot phut. Thuc te' khi mau roi khoi than van con mot luong nho PAH d trong mau, cho nen clearance huyet tuong cua PAH do duoc trong cac thuc nghiern khac nhau chi bang khcang 90% lucng huyet tuong thuc su da mang PAH di vao than. Nhu v~y luu hrcng

huve' h? h~ 1 hut ls 585x100 650 1 T' d' 'th;'>t' h 1

uyet tuong c ay qua t an trong P u a 90 = m. U 0 co e III ra uu

hrcng mau toan phan qua than m6i phut dua tren luu lucng huyet tuong qua than va hematocrit. Ne'u hematocrit la 45% thi luu lucng mau qua than la:

650ml x 100 = 1182 ml/phut

55

23

THAN DIEU HOA NONG DO THAM THAU CVA DICH NGOAI BAo.

, . ..

CHUC NANG PHA LOANG V A CO D~C xuoc TIEU CVA TH~N

MQt trong nhfrng chuc nang quan trong cua than la kiern so at nong dQ tham thau cua dich ngoai bao. Khi nong dQ tham thau giarn (dich loang), cac co che dieu hoa than kinh va hormon S8 kich thich than tao ra nude ti~u loiing, nude bi dao thai khoi co th~ va nong dQ tharn thau cua dich ngoai bao tang trd ve rmrc binh thuong. Nguoc lai khi n6ng dQ tharn thau qua cao, than S8 tao ra nuoc ti~u co dac, cac chat hoa tan bi dao thai khoi co th~ trong khi nude duoc gift lai lam cho nong dQ tharn thau giarn ve rmrc binh thuong.

Tin hieu d~ bao cho than biet can phai tao ra nude ti~u loang hay dac la hormon ADH (antidiuretic hormon, cung goi la vasopressin), do vung dudi d6i san xuat va duoc du trfr d thuy sau tuyen yen. Khi nong dQ tharn thau cua dich ngoai bao qua cao, thuy sau tuyen yen bai tiet nhieu ADH, than S8 bai xuat nhieu chat hoa tan va gift nude lai. Nguoc lai khi nong dQ tharn thau giarn ADH khong duoc bai tiet.

1. co CHE T1\O NUOC TIEU LOA.NG CVA TH~N

Binh thuong nong dQ tharn thau cua dich loc cau than dung bang cua huyet tuong, bang' khoang 300 mOsmllit. Neu can phai bai xuat nude thua ra khoi co th~, thi phai pha loang dich loc cau than khi n6 di qua ong than, nghia la cac chat hoa tan phai duoc tai hap thu nhieu hon nuoc. Doan day nhanh len cua quai Henle va dean pha loiing cua ong luon xa binh thuong khong tham nude. Can doan cuoi cua ang luon xa, ang g6p vung vo va ang g6p cung trd ne~ hoan toan khong tha~ nude khi khong co ADH trong mau tuan hoan. Nguoc lai, su tai hap thu cac chat hoa tan d cac dean nay lai rat manh va theo co che van chuyen tich cue. Su tai hap thu tich cue cua ion Na +, Cl, K+ d dean day cua nhanh len quai Henle trong khi nuoc duoc gift lai, lam cho kha nang tharn thau cua dich khi ra khoi quai giarn xuong chi can 100 mOsm/i. Khi dich qua orig luon xa, ang gop vung va va ang gop, mot so chat hoa tan dac biet la ion Na + can duoc tai hap thu them lam cho dich ang cang bi pha loang them, kha nang thfrm thau cua dich ong gop d6 VaG b~ than chi can bang 65 mOsm/lit.

2. CO CHE Co I)~C NUOC TIEU CVA TH~N

Than co mot co che' rat d:fJ.c biet va rat phirctap d~ co d:fJ.c nude ti~u goi la co che nhan nguoc dong. Co che nay dua tren su s:1p xep giai phau cua quai Henle va quai mach thang (vasa recta) d vung tuy than (Hinh 6-7).

24

J 1110 3na --

IMach tM;'g I I . I· l, , I

(V~S8recta ) .Ojcn ke I rUBI Henle O(chlre Ong gop

Hinh 6-7. Co chi ngudc dong co d"¢ic nude tie'u

o nguoi c6 khoang 1/3 den 1/5 so nephron c6 quai Henle di sau vao vung tuy than rai lai quay trd ve vung vo than. Song song vdi nhiing quai Henle rat dai nay la nhirng mao mach quanh ong goi la mach thang. Cac quai mach nay cung tu vung va di vao vung tuy rai trd lai vung vo.

Co che co dac nude ti~u phu thuoc VaG su duy tri mot bac thang tharn thau tang dan tU vung va VaG vung tuy than. Bac thang nay duoc duy tri nho hoat d9ng cua quai Henle nhu mot h~ thong nhan nguoc dong va hoat dong cua mach th&ng nhu mot he thong trao d6i nguoc dong. H~ thong nguoc dong la mot h~ thong trong do dong di VaG chay song song, nguoc chieu va rat gin vdi dong di ra trong mot khoang nao day.

Hinh (6-8) minh hoa hoat d9ng cua mot h~ thong nguoc dong. 0 ben trai, nguon nhiet bao quanh ong d§.n va lam tang nhiet d9 cua nude chay trong ong d§.n len den lOoC. 0 ben phai, nguon nhiet duoc dat VaG ong d§.n di'i duoc uon cong thanh quai hinh chir U, vdi dong chay VaG d canh dong chay ra. Nhiet d dong chay ra lam n6ng dich trong dong chay VaG lam cho khi dong nay chay den nguon nhiet d chop quai hinh chfr U thi nhiet d9 cua n6 la 90°C chu khong phai 30°C nhu hie mdi chay vao. Do do luc nay nguon nhiet lam tang nhiet d9 cua dich trong dong chay VaG tU 90°C len 100°C chir khong phai tir 30°C len 40°C.

Quai Henle ciing hoat d9ng theo each tuong tv. Nhanh xuong quai Henle khong tharn cac chat hoa tan nhung c6 tinh tham cao voi nuoc, do do nude van chuyen VaG dich ke va nang d9 cua Na+ trong ong tang len. Ngoai ra mot so ure cung di VaG nhanh xuong lam cho kha nang tharn thau cua dich ong cang tang. Dean mong cua nhanh len khong tharn nude va tharn vua phai vdi Na + va ure, nhung tharn Na + nhieu hon ure, Ket qua la Na + van chuyen thu dong VaG dich ke theo bac thang

25

n6ng dQ. D09-n day nhanh len quai Henle khong tharn ca nude va chat hoa tan, nhung d doan nay ca cr va Na + duoc van chuyen tich eire ra khoi dich ang, Nat duoc born VaG dich ke nho born Na +, K+ - ATPase, can cr duoc van chuyen tich cue thu ph at cung vdi Na + (co che d6ng van chuyen cung chieu), Cac ang g6p vung va khong' tharn ure, nhung tharn nude vdi su c6 mat cua ADH. Ket qua la nude ra khoi ang va nong dQ ure trong ang g6p tang len. Cac ang g6p vung tuy trong tham ure va tham ca nude voi su c6 mat cua ADH, ure van chuyen thu dong' VaG dich ke d~ duy tri nong dQ tharn thau cao d thap tuy; nude duoc tai hap thu lam cho dich trong ong g6p bi co dac.

--'01:;;::===

~h~ ~

JO 40

30' 70
1
JOC
t
I - ~ := 100\
-
- ~ ....
fa'
1
N.f
n
40C
t 100 C~ljph';t

Hinli 6-8. So dd h~ th{/ng nguc;Jc dong

Nhung bac thang tharn thau trong thap tuy se khong t6n tai lau neu Na +, ure va cac ion khac bi dong mau cuon di. Cac chat hoa tan nay duoc gift 19-i d thap tuy vi hai ly do: (1) hru luong mau vung tuy than rat thap, chi bang 1 den 2% hru luong mau than, do do n6 khong c6 kha nang cuon theo cac chat hoa tan d vung tuy, (2) cac mach thang hoat dong' nhu nhirng h~ thong trao d6i nguoc dong: khi mau chay xuong theo nhanh xuong cua mach thang, ion Na + va ure se khuech tan tu dich ke VaG mau, trong khi nude khuech tan tU mau VaG dich ke. Ca hai qua trinh nay lam cho nong dQ tharn thau trong mau mao mach tang dan len den muc tai da In. 1200mOsm/l d ch6p cua mach thing, r6i khi mau chay len theo nhanh len thi tat ca Na +, cr va ure se khuech tan tU mao mach VaG dich ke. trong khi nude di VaG mao mach. Nhu v~y khi mau cua mach thing roi khoi vung tuy nong dQ tham thau cua mau chi hoi cao hen nong dQ tham thau cua mau di VaG mach thing d vung va.

26

Dieu do c6 nghia la mau chay qua mach thang chi mang mot luong rat nho cac chat hoa tan ra khoi vung tuy. Trao d6i nguoc dong d mach thang' la mot qua trinh thu dong. Qua trinh nay phu thuoc VaG su khuech tan cua nude va cac chat hoa tan qua thanh cua mach thang' theo ca hai huong va bac thang tharn thau d vung tuy se khong duoc duy tri neu qua trinh nhan nguoc dong trong quai Henle ngung lai.

- Vai tro cua ADH trong co che co dac nude ti~u. Khi nang d9 ADH trong mau tang cao, cac te bao bieu mo cua ang g6p vung va, ang g6p vung tuy va ang g6p trd nen rat tharn nuoc. Vi vay, khi dich chay qua ang g6p, nude se khuech tan tU long ang VaG dich ke theo bac thang tham thau, rai lai tU dich ke khuech tan VaG nhanh len cua mach thang' va di VaG tuan hoan chung. Ket qua la dich trong ang bi co dac. Khi dich chay VaG b~ than, nang d9 tharn thau cua dich VaG khoang 1200 mOsm/l, dung bang nang d9 tharn thau cua cac chat hoa tan d vung tuy trong cua than.

NHUNG ROI LO~N LAM SANG eVA TH~N

Ve mat sinh 15' h9C, nguoi ta chia cac benh than thanh narn loai:

- Buy than cap: than ngung hoat dong hoan toan hoac gfrn nhu hoan toano

- Buy than man: cac nephron bi pha huy dan dan cho den khi than khong th~

thuc hien duoc moi chuc nang.

- Benh than c6 kern theo tang huyet ap: cac t6n thuong cua cau than hoac t6n thuong mach mau gay tang huyet ap nhung khong gay suy than.

- H9i chung than hir: mang cau than trd nen tham hon binh thuong lam cho met

lucng len protein bi mat theo nUDC ti~u. r

- Nhirng bat thuong cua than gay rai loan tai hap thu mot so chat.

Cac loai benh than k~ tren thuong gay ra mot so trieu chung chung nhu trong nude ti~u c6 protein, bach cau, hong cau; than mat kha nang co dac hoac pha loang nUDC ti~u, ure huyet; nhiern toan va tang tai hap thu Na + mot each bat thucng.

1. PROTEIN NI~U

Trong nhieu benh than, tinh tham cua mao mach cfru than tang len lam cho protein xuat hien trong nude ti~u. Hau het protein nay la albumin, nen trudc day can goi la albumin nieu. Trong benh viern than, cac dien tich am trong mang 19C cau than bi tieu huy nen khong can duoc su tharn cac phan tli albumin qua cac 16 19C (protein cung tich dien am trong khi kich thUDC cac 16 19C khong thay d6i). LUQng protein trong nude ti~u c6 th~ rat Ion, dac biet trong hoi chung than hu lucng protein bi mat VUQt qua luong protein huyet tuong duoc t6ng hop d gan. Ket

27

qua la protein huyet tuong giarn, ap suat keo gram, th~ tich huyet tuong giam trong khi dich u dong d cac rna gay phu. 6 mot so nguoi blnh thuong c6 th~ xuat hien protein nieu neu ho dung lau, goi la protein nieu do dung. Khi ho narn xuong thi trieu chung nay bien mat. Nhirng thay d6i huyet dong' h9C cua than gay protein nieu con chua duoc sang to.

2. TH~N MAT KHA. NANG co f)~e vA PHA LOANG Nuoe TIEU

Trong benh than, nude ti~u trd nen it co di;tc, th~ tich nude ti~u thuong tang gay trieu chung dai nhieu va dai darn, Th~ tich nuoc ti~u tang nhung nang d9 th:lm thau cua nude ti~u lai trd nen co dinh VaG khoang bang nang d9 tharn thau cua huyet tuong, dieu d6 chung to ca hai kha nang co dac va pha loang nude ti~u cua than deu bi mat, mot phan do co che nguoc dong hi roi loan, nhung mot nguyen nhan quan trong hen la su mat cac nephron. Khi m6 cat bo mot than, so nephron chi' con lai mot nita, hoac trong suy than man so nephron giarn dan. Cac nephron con lai thuong bi qua tili do cac nguyen nhan sau. Trude hit luu lucng mau qua than va luu lucng 19C cau than d m6i nephron tang tir 50 den 100%. Nguoi ta con chua biet ly do tai sao c6 su tang nay. Hai la mot luong rat IOn cac chat bai tiet nhu ure, phosphat, sulphat, acid uric, creatinin v.v. tich Iiiy lai trong dich ngoai bao lam tang kha nang tai cua ong than doi vdi nhimg chat it duoc tai hap thu, len tdi 1000%. Do d6 chi mot phan nho nhirng chat hoa tan duoc tai hap thu dong than, So con lai tac dung nhu nhirng chat loi ti~u tham thau lam cho dich chay rat nhanh qua ong than. Ket qua la th~ tich nude ti~u d m6i nephron cao gap 20 15.n binh thuong va luong nude ti~u cua benh nhan tang gap 2 den 3 Ian binh thuong. 'I'inh huang nghich ly nay la do su tang th~ tich nuoc ti~u cua tung nephron IOn hen

r

nhieu so vdi su giarn so luong nephron. Su chay qua nhanh cua dich qua ong than

lam cho co che' co dac va pha loang cua than khong heat dong' tot. Khi hau het cac nephron bi pha huy, th~ tich nude ti~u giarn, benh nhan bi dai it hoac va nieu.

3. TANG URE HUYET

Khi cac san pharn phan giai cua chuyen h6a protein tich lai trong mau, hoi chung ure huyet cao xuat hien, Trieu chung ure huyet cao bao gam: met moi, chan an, buon non, non rmra, roi loan tam than, hay nharn l§.n, co giat co va han me. Trong ure huyet cao man tinh, trieu chung thieu mau rat r6 do qua trinh sinh hong cau bi giarn. Ncng d9 nito cua ure mau, nito phi protein va creatinin rat cao. MQt so chat d(k khac nhu cac acid hiru co hoac phenol ciing tich luy trong co th~ va gay ra nhirng trieu chung cua ure huyet cao. Nguoi ta dung ky thuat tharn ph an mau cho nhirng benh nhan ure huyet cao d~ lay di nhimg chat dQC va keo dai doi song cho benh nhan,

28

4. NHIEM TO A:\,

Nhiern toan (acidosis) la trieu chung thuong gi[tp trong benh than man tinh do than khong c6 kha nang bai xuat cac san pham acid cua tieu h6a va chuyen h6a. Moi ngay qua trinh chuyen h6a cua co th~ san xuat ra cac acid chuyen h6a nhieu hon cac kiern chuyen h6a khoang 50 de'n SOmmol. Do d6 khi than khong heat dong acid se tich hiy lai trong co th~. Binh thuong cac h~ dern cua dich ngoai bao va ndi bao c6 th~ dern duoc khoang 500 den 1000 mmol acid, va pH cua dich ngoai bao khong bi giarn d9t ngot den rmrc nguy hi~lll. Cac hop chat phosphat cua xuong cling c6 th~ dern them khoang vai nghin mmol, nhung kha nang dern nay bi can di nhanh chong, lam cho p H giarn rat manh, benh nhan se bi hen me do nhiern toano

5. ROI LOAN CHUY(~N HOA Na+ TRONG B(~~H TH~N

Nhieu nguoi bi benh than c6 trieu chung gift Na I qua nhieu va bi phu, C6 ba nguyen nhan gay gift Na +: (1) trong benh viern cau than cap, lucng Na' 19C qua mang diu than giam trong khi luong Na + duoc tai hap thu kh6ng giam tuong ung, (2) trong hdi chung than hu, protein huyet tuong giam, nude khuech tan tU rnau VaG khoang ke lam cho th~ tich huyet tuong giam, kich thfch h~ thong reninangiotensin lam tang bai tiet aldosteron cua vo thuong than, aldosteron gay tang tai hap thu Na + d ong than, (3) mot so benh than gay tang huyet ap, tang huyet ap d§.n den suy tim. Suy tim d giai dean d:lu benh nhan kh6ng c6 bi~u hien gi 11k nghi ngoi nhung neu ho lao dong, luu luong tim tang len se gay ra nhimg thay d6i phan xa trong tuan hoan bao gam co mach da, mach lach, mach than va lEUTl giarn luu luong mau qua than ket qua la Na' bi gift lai co th~.

THAM DO CHUC NANG TH~N

1. NGHI¢M PHAp DO CLEARANCE HUy:frT TVONG CUA INULIN, MAN."'ITOL,

, ,~ '" ~ ",/ '"

PAH VA CUA MOT SO CHAT KHAC

Neu do clearance cua tat ca cac chat do ta c6 th~ xac dinh duoc luu lucng 19C cau than, luu luong rnau qua than trong mot phut, phan so 19C.

Tuy nhien nhieu nghiern phap do clearance rat kh6 thuc hien. Hai nghiern phap tharn do clearance dac biet hay duoc dung la chup b~ than can Quang va do clearance cua cac chat dang vi ph6ng X~.

- Chup b~ than can Quang: mot so chat c6 chua iod nhu Dicdrast, Hippuran, Lopax khi tiern VaG co th~ se duoc 19C qua mang cau than va duoc bai tiet tich cue d ong than va trong vong vai phut chung xuat hien trong nude ti~u vdi nang dQ rat

T3 - SLH

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cao. Tren phim X quang c6 th@ thay duoc bong cua b@ than, cua nieu quan va bang quang. Thong thuong nhirng chat nay ducc loc sach sau khi tiern 5 phut va b6ng cua b@ than se r6 rang. Neu trong thoi gian nay rna hinh anh khong r6 net thi chung to clearance cua than bi giam.

- Clearance cua cac chat ph6ng xa.

Neu cac chat k@ tren duoc u voi iod ph6ng xa, ta c6 th@ do duoc hoat tinh ph6ng xa tU hai b@ than bang each dat may dem ph6ng xa d tren than. 'I'iern mot luong rat nho hop chat phong xa van tinh mach roi ghi lai hoat tinh ph6ng xa trong vong vai phiit tiep theo d@ xac dinh clearance cua than.

Hai nghiern phap tren c6 th@ dauh gia duoc chuc nang cua tung than mot each dQc lap.

2. DO NONG 0(> cAc CHAT TRONG MAu DE DANH GIA CH1JC NANG TH~N

- Binh thudng nong d9 ure trong mau la 26 mg/ 100 ml. Trong suy than nang, ndng dQ ure huyet c6 th@ tang len den 300 mg/ 100 ml.

- N6ng d9 creatinin huyet binh thuong la 1,1 mg/ 100 ml, n6 c6 th@ tang len 10 Ian trong suy than nang.

- Nguoi ta cling c6 th@ dung d6 thi pH-bicarbonat d@ xac dinh rnuc d9 acidosis chuyen h6a do roi loan chuc nang than.

3. PHAN TICH cAc TINH CHAT LV H6A c(rA NUdc Tu1u HE DA~H GIA CHV'C NANG TH~~

- Do th@ tich nude ti@u m6i ngay. Trong suy than cap th@ tich nude ti@u c6 th@ giarn xuong. Suy than man th@ tich nude ti@u cung giarn. Nhung suy than vua phai c6 th@ lam tang luong nude ti@u do su van chuyen nhanh cua dich trong ong than cua cac nephron da bi pha huy.

- Do ti trong cua nude ti@u. Tuy theo loai chat duoc loc, ti trong cua nude ti@u c6 th@ thay d6i rat nhieu: cao nhat la 1,045, thap nhat la 1,002. D@ danh gia kha nang pha loang nude ti@u cua than, ta cho benh nhan uorig nhieu nude r6i do ti trong thap nhat c6 th@ dat ducc, Sau d6 trong mot xet nghiern khac, nguoi ta cho benh nhan nhin nUDC trong 1/2 gid r6i do ndng d9 toi da cua nude ti@u. Kha nang co d~c nude ti@u cua than la thong so chuc nang phan anh so Iuong nephron bi giarn.

cAc CHAT L(H TlEU vA co CHE TAc Dl)NG

NgUdi ta dung thuoc loi ti@u d@ lam g ia m luorig d ich trong co th@ khi b i ph u ho ac tang huyet ap, H:1u het chat lei ti@u lam g ia rn toc dQ tai hap thu

30

d ich d ong th a n. Dieu quan trorig khi dung th uoc lei ti~u la toe dQ d ao thai Na ' cuug ph a i b aug toe dQ dao thai nude, vi neu chi c6 n udc b i d ao thai thi d ich n g o a i b ao se trd nen uu tr uorig v a kich thich b ai tiet ADH, hormon nay lam tang tai hap thu n udc d ong tha n va lam mat tac d ung lei ti~u. DUGi day l a uhfiug lo a i th uoc lei ti~u th uong dung:

,,~ ,:?,,? ,,"

I. TIIUOC L(JI TIEU TIIAM TIIAU

'I'iern ure, mannitol, sucrose hoac cac chat khoug duoc tai hap tlm d~ dang dong than se lam tang cac chat c6 tac dung tham thau d ong than, nude duoc gift lai trong ong va bai xuat theo nude ti~u.

2. TIIUOC LQl T1EU LAM GIAM TAIlIlp TIIU rictt ClIC

Cac chat nay ire che h~ thong cac chat mang trong cac te bao bi~u mo ong than nen lam giam su tai hap thu tich cue cua cac chat hoa tan trong orig, ap suat tharn thau cua dich ong tang len va gay loi ti~u tharn thau. Vi du:

- Furosemid uc che qua trinh d6ng van chuyen Na I, cr d mang ong cua te bao bi~u mo doan day nhanh len quai Henle va dean pha loang cua ong luon xa, do do lam giam su tai hap thu tich cue cua Na' va cr. Cac ion nay duoc dua den cac phan cuci cua ong than, tac dung nhu nhimg tac nhan tham thau va ngan can su tai hap thu tU quai Henle VaG dich ke, lam giarn bac thang tharn thau cua dich ke vung tuy than, nen kha nang co dac cua than giam, su tai hap thu cua nuoc dong g6p cang giarn hon. Ket qua la 20 den 30% dich loc cau than duoc bai xuat VaG nude ti~u lam cho lucng nude ti~u c6 th~ nhieu gap 25 Ian binh thuong.

- Chlorothiazid: ngan can su tai hap thu tich cue cua Na I dong luon xa.

3. TIIUOC L(JI T1EU ttc CIIE MEN CARBONIC ANIIYDRASE (CA)

Diamox uc che men CA nen ngan can sV tai hap thu ion HCOa- dong luon gan.

HCO:i- d lai trong ong than c6 tac dung nhu mot chat lei ti~u tharn than. Dung thuoc nay c6 th~ gay nhiern toan do su dao thai nhieu HCOa- ra nude ti~u.

4. NllilNG ClIlT ttc CHE CJ).NII TRANII VOl ALDOSTERON: SPIRONOLACTON

Spironolacton canh tranh VGi aldosteron d~ chiern receptor d te bao bi~u mo orig luon xa, do do ngan can tac dung tang tai hap thu Nal cua aldosteron. Na' bi gift lai oug tac dung nhu mdt chat lQi ti~u thfrll1 thau, Thuoc nay cfing iic che tac dung tang bai tiet K+ VaG ong than nen trong mot so trucng hop c6 th~ gay tang nong dQ K' dich ngoai bao tdi rrnrc nguy hiern cho co th~.

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CIIUONG 7

SINH L Y NOI TrET

DA.I ClfONG VE H¢ N(n TlET V A HORMON

Chuc nang cua co th~ duoc dieu hoa bang hai he thong chu yeu do la h~ thong than kinh va h~ thong th~ dich.

Vai tro dieu hoa cua M thong than kinh se dU<;JC de cap den trong chuong 10 va 11. H~ thong th~ dich dieu hoa chuc nang cua co th~ bao gam nhieu yeu to nhu th~ tich mau, cac thanh ph an cua mau va th~ dich nhu nang dQ cac loai khi, nang dQ cac ion dac biet la nang dQ cac hormon noi tiet, Chinh vi v:%ty h~ thong th~ dich can duoc goi la h~ thong noi tiet.

Nhin chung he thong noi tiet chu yeu dieu hoa cac chuc nang chuyen h6a cua co th~ nhu dieu hoa toc dQ cac phan ling h6a h9C d te bao, dieu hoa su van chuyen vat chat qua mang te bao hoac cac qua trinh chuyen hoa khac cua te bao nhu su ph at trien, su bai tiet, Tuy nhien tac dung dieu hoa cua cac hormon thi khong giong' nhau. MQt so hormon tac dung xuat hien sau vai giay trong khi mot so hormon khac lai can vai ngay nhung sau d6 tac dung c6 th~ keo dai vai ngay, vai tuan tharn chi vai thang.

Giua h~ thong nQi tiet va h~ thong than kinh c6 mdi lien quan tuong h6. That vay, it nhat c6 hai tuyen bai tiet hormon dudi tac dung cua kich thich than kinh nhu tuyen thuong than va tuyen yen, Dong thoi cac hormon vung dudi dai lai duoc dieu hoa bai tiet bdi cac tuyen noi tiet khac.

1. DlNH NGHIA

1.1. D~H NGHIA TUYEN N('H TIET

Khac vdi cac tuyen ngoai tiet nhu tuyen nude bot, tuyen tVY ngoai tiet, tuyen da day .... 1a nhirng tuyen c6 ong dan, chat bai tiet duoc d6 vao mot co quan nao do qua

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aug tuyen; tuyen noi tiet lai la nhirng tuyen- khong c6 ang dan, chat bai tiet dude dua VaG mau rai duoc mau dua den cac co quan, cac rna trong co th~ va gay ra cac tac dung d do.

Cac tuyen noi tiet chinh cua co th~ gam vung dudi d6i, tuyen yen, tuyen giap, tuyen can giap, tuyen tuy n9i tiet, tuyen thuong than, tuyen sinh due nam va nii, rau thai (Hlnh 7.1).

Lye;; yea

.... ~--¥-J.--+-- Toy&' 7'1!(/_dl7g th#fl

Hinh 7-1.Cac tu.yen. noi tiet

1.2. D~NH NGHIA HORMON

Hormon la nhirng chat h6a h9C do mot nhorn te bao hoac mot tuyen n9i tiet bai tiet VaG mau rai duoc mau dua den cac te bao hoac cac rna khac trong co th~ va gay ra cac tac dung sinh ly d do,

2. PHAN L01\I HORMON

Dua VaG noi bai tiet va noi tac dung nguoi ta phan cac hormon thanh hai loai do la harmon tai cho (harmon dia phuong) va harmon cua cac tuyen nQi tiet.

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2.1. HORMON T~I em)

Hormon tai ch6 la nhirng hormon do mQt nh6m te bao bai tiet vao mau r6i duoc mau dua den cac te bao khac d gan noi bai tiet d~ gay ra cac tac dung sinh ly.

Vi du:

- Secretin: Do te bao thanh ta trang bai tiet, duoc mau dua den tuy d~ kfch thfch tuy bai tiet dich tuy loang,

- Cholecystokinin: Do te bao thanh ruot non bai tiet r8i duoc rna u dua den tui mat d~ lam co tui mat d8ng thoi duoc mau dua den tuy d~ kfch thich tuyen tuy bai tiet dich tuy c6 nhieu men tieu hoa.

- Histarnin: Do cac te bao d nhieu rna trong co th~ dQ.c biet rna da, phci, ruot bai tiet vao mau, Histamin c6 tac dung gian mach va lam tang tfnh tham cua mao mach.

- Prostaglandin: La san pham bai tiet cua hau het cac rna trong co th~, c6 tac dung gian mach (cling c6 hie gay co mach) va lam tang tinh tham cua mao mach,

2.2. HORMON ellA eAe TUYEN NOI TIET

Khac vdi cac hormon tai ch6, cac hormon cua cac tuyen ndi tiet thuong duoc mau dua den cac rna, cac co quan d xa noi bai tiet va gay ra cac tac dung sinh ly d d6.

Cac hormon do cac tuyen noi tiet bai tiet lai duoc phan thanh hai loai khac nhau:

- MQt s6 hormon c6 tac dung len hau het cac rna d trong co th~ nhu hormon GH cua tuyen yen, T3, T4 cua tuyen giap, cortisol cua tuyen vo thuong than, insulin

cua tuyen tuy n9i tiet.... '

- MQt s6 hormon chi c6 tac dung dQ.c hieu len mot rna hoac mot co quan nao do nhu hormon ACTH, TSH, FSH, LH ... cua tuyen yen. Cac rna hoac co quan chiu tac dung dQ.c hieu cua nhimg hormon nay duoc goi la rna hoac co quan dich.

Cac hormon cua cac tuyen n9i tiet chfnh cua cd th~ la :

- Vung dudi d8i: Bai tiet cac hormon giai ph6ng va uc che' , hai hormon khac

duoc chua d thuy sau tuyen yen la ADH (vasopressin) va oxytocin.

- Tuyen yen: Bai tiet GH, ACTH, TSH, FSH, LH, Prolactin.

- Tuyen giap: Bai tiet T3, T4, Calcitonin.

- Tuyen can giap: Bai tiet parathormon (PTH).

- Tuyen tuy noi tiet: Bai tiet insulin, glucagon.

- Tuyen vo thucng than; Bai tiet cortisol, aldosteron.

- Tuyen tuy thuong than: Bai tiet adrenalin, noradrenalin.

- Tuyen buong trung: Bai tiet estrogen, progesteron.

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- Tuyen tinh hoan: Bai tiet testosteron.

- Rau thai: Bai tiet HCG, estrogen, progesteron, HCS, relaxin.

3. BAN CHAT H6A HOC CVA HORMON

Cac harmon thuong co ban chat hoa h9C thuoc mot trong ba loai sau day:

- Steroid: Day la nhimg harmon co cau true hoa h9C giong' cholesterol va hau het duoc t6ng hop tU cholesterol nhu harmon duoc bai tiet tu tuyen va thuong than (cortisol, aldosteron), tir tuyen sinh due (estrogen, progesteron, testosteron).

- Dfin xuat cua acid amin la tyrosin: Hai nhorn harmon duoc t6ng hop tU tyrosin do la harmon cua tuyen tuy thuong than (adrenalin, noradrenalin) va harmon cua tuyen giap (T3, T 4).

- Protein va peptid: H~u nhu tat ca cac harmon con lai cua co th~ thi hoac la protein, hoac la peptid, hoac la dan xuat cua hai loai nay nhu cac harmon vung dudi d6i, harmon tuyen yen, harmon tuyen can giap, harmon tuyen tuy nQi tiet va hau het cac harmon tai ch6.

4. DVTRUVA BAI TIET HORMON

4.1. HORMON STEROID

Cac harmon cua tuyen va thuong than, tinh hoan, buong trung thuong chi duoc du trfi mot 111Qng rat nho d te baa tuyen con lai phan IOn chung thuong d duoi dang ti&n chat nhu cholesterol hoac cac dang trung gian giua cholesterol va san pharn harmon cuoi cling. Khi co nhirng kich thich phu hQP, dudi tac dung cua cac enzym co trong te baa, chi sau vai phut, chting duoc chuyen thanh da ng harmon cudi cling va duoc bai tiet hftu nhu ngay l$.p tuc,

4.2. DAN XUAT eVA TYROSIN

Hai nhorn harmon tuy thuoug than va tuyeu giap dgu d uQc t6ng hop duoi tac dung cua he thong enzym co trong baa tuong cua te bao tuyeu nhung each du tru va bai tiet cua hai nhorn harmon nay lai kh6ng giong nha u.

- Nhorn harmon tuy thuong than sau khi duoc t6ng hQP, chung duoc hap thu vao cac tui nho va duoc du trii d do cho den khi ducc bai tiet.

- Nhorn harmon tuyen giap sau khi ducc t6ng hop chung duoc dua vao long nang giap. T'ai day, chung thucng g&n vci phan tli protein Ion la thyroglobulin va dltqC du trii d day. Khi harmon duoc bai tiet, trong te baa tuyen giap co cac enzym tieu hoa phan thyroglobulin va giai phong T3- T4 vao mau.

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4.3. HORMON PROTEIN vA PEPTID

Nh6m hormon protein hoac peptid thucng ducc hinh thanh d luci n9i bao cua te bao tuyen. Dau tien chung duoc t6ng hop thanh nhirng tien hormon, day la nhirng phan ttt protein len hon nhieu so voi phan tir hormon d dang hoat dong va duoc goi la preprohormon. Sau do nhirng phan ttt nay duoc tach ra thanh nhirng phan tir nho hen goi la prohormon. Cac phan ttt prohormon se duoc van chuyen tU cac tui cua luoi ndi bao den b9 Golgi va d day cac phan ttt protein tiep tuc duoc dit nho hen, Bang each nay, cac phan ttt hormon d dang hoat dong c6 ban chat hoa hQC la protein duoc tao thanh. B9 Golgi thuong chua cac phan ttt hormon van cac tui nho c6 mang hinh con nhong duoc goi la cac tui che tiet hoac cac hat che' tiet. Nhirng tui che tiet nay duoc du trfr d bao tucng cua te bao tuyen cho den khi c6 nhfrng tin hieu d(lc biet nhu tin hieu than kinh, tin hieu th~ dich, tin hieu co hoc hoac hoa hoc tai ch6 thi cluing S8 duoc bai tiet.

Do each du trfi va bai tiet cua cac loai hormon khac nhau nen thoi gian bai tiet hormon sau tin hieu kich thich hay thoi gian xuat hien tac dung dau tien cling nhu tac dung day du cua cac hormon cling khong giong nhau.

M9t so hormon nhu adrenalin, noradrenalin duoc bai tiet vai giay ngay sau khi c6 tin hieu kich thich va cluing phat huy tac dung day du sau vai giay cho den vai phut.

M9t so hormon khac nhu T3- T4 duoc du trf! dudi dang cau true thyroglobulin trong long nang giap dai khi den vai thang truce khi duoc bai tiet van mau. Sau khi duoc bai tiet vai gid tharn chi vai ngay sau rnoi xuat hien nhirng tac dung dau tien va nhieu khi phai sau vai tuan den vai thang mdi th~ hien tac dung day duo

S. cHkr TIEP NH~N HORMON T1).1 TE nAo UiCH (RECEPTOR)

Khi den te bao dfch, cac hormon thucng khong tac dung true tiep van cac cau true trong te bao d~ dieu hoa cac phan ung h6a hoc d ben trong te bao rna chiing thuong giin voi cac chat tiep nhan - cac receptor d tren be mat hoac d trong te bao dich.

Phuc hop hormon-receptor sau do S8 phat dong mot chuoi cac phan irng h6a hoc d trong te bao theo ki~u phan ung sau bao gid cling ma nh hen phan ung truce sao cho chi can nhfing kich thich ban dau rat nho cua hormon cling du gay duoc hieu qua cudi cling rat Ion.

Tat ca hoac hau nhu Hit ca receptor deu la nhfing ph an ttt protein c6 trong luong phan ttt Ion. M6i te bao dfch thucng co khoang 2000-100.000 receptor.

Moi receptor thuong dac hieu vdi mot hormon, chinh dieu nay quyet dinh tac dung dac hieu cua hormon len rna dfch. V~y rna dfch chiu tac dung cua hormon chinh la mo c6 chua cac receptor d(lc hieu tiep nhan hormon d6.

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Cac receptor tiep nhan cac 10<.J.i hormon khac nha u c6 th~ narn d cac vi trf sa u.

- 0 tren bg mat hoac d trong mang te bao: Day la cac receptor tiep nhan hau het cac hormon protein, peptid va catecholarnin.

- 0 trong bao tucng: cac receptor narn trong bao tuong la nhirng receptor tiep nhan cac hormon steroid.

- 0 trong nhan te bao: Day la nhirng receptor tiep nhan hormon T3- T1 cua tuyen giap. Nguoi ta cho rang cac receptor nay c6 th~ narn tren mot hoac nhieu chromosom trong nhan te bao dich.

S61uQng cac receptor d te bao dich c6 th~ thay deli tung ngay tharn chi tung phut boi vi cac phan tv protein receptor tv n6 c6 th~ bi bat heat hoac bi pha huy trong qua trinh heat dong nhung r6i chung lai c6 th~ duoc heat hoa trd lai hoac hinh thanh cac phan tv mdi nho co che t6ng hop protein trong te bao.

Neu khong c6 su thay deli thuong xuyen cua receptor thi viec g:1n lien tuc cua hormon vdi receptor d te bao dich se dan den tinh trang giarn so luong receptor do mot sO' thi bi bat hoat hoac do giarn san xuat cac phan tv receptor moi. Trong truong hop nay nguoi ta n6i day la ki~u dieu hoa lam giarn luong receptor (downregulation). Hien tirong nay se lam giarn tinh dap ung cua rna dich voi hormon vi sO' luong receptor hoat dong bi giarn.

Trong mot sO' truong hop khac, hormon lai c6 th~ gay ra su digu hoa lam tang sO' luong receptor (up-regulation). D6 la do hormon kich thich lam tang tao cac phan tv receptor moi nhieu hen so voi binh thuong. Truong hop nay nguoi ta n6i rna dich trd nen nhay cam hon voi tac dung kich thich cua hormon.

6. eo CHE TAc Dl)NG ellA HORMON

Sau khi hormon g<1n vdi receptor tai te bao dich, hormon se hoat h6a receptor, n6i each khac la lam cho receptor tv n6 thay deli cau true va chuc nang. Chinh nhirng receptor nay se gay ra cac tac dung tiep theo nhu lam thay deli tinh tham mang te bao (mo kenh hoac dong cac kenh ion), hoat h6a h~ thong men d trong te bao do hormon g:1n voi receptor tren mang te bao, hoa t hoa h~ gien do hormon g:1n voi receptor d trong te bao.

Tuy thuoc vao ban chat hoa h9C cua hormon rna vi trf g:1n cua hormon voi receptor se xay ra d tren mang, trong bao tuong hoac trong nhan te bao va do do chung cling c6 nhirng con duong tac dorig khac nhau vao ben trong te bao hay n6i each khac, chung c6 nhirng co che tac dung khac nhau tai te bao dfch.

6.1. co eHE T Ae Dl)NG CVA cAc HORMON GAN vor RECEPTOR TRf~N MA.NG TE UA.O

H5.u het cac hormon c6 ban chat hoa h9C la protein, peptid, dan xuat cua acid arnin khi den te bao dich dgu g:1n voi cac receptor narn ngay tren mang te bao.

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., ., .,,,

Dac diem cua cac receptor nay la c6 nhirng vi trf dac hieu d phia ngoai mang de

giin voi hormon va c6 mot phan 16i VaG trong bao tuong. Ph§.n 16i VaG trong nay thucng c6 kha nang hoat dong nhu mot men xuc tac neu d11<;lC hoat h6a. Nguci ta g9i cac receptor nay la loai receptor xuyen mang dac hieu (Hinh 7.2).

M9t so receptor khac lai hoat d9ng nhu cac protein kenh, Khi hormon giin vdi loai receptor nay n6 se lam thay d6i cau true khong gian cua receptor va lam md kenh ion.

H

V

H W

rv ry rvr-
R R
l- IT
I E E
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, ?rofelrJ _;Yros/neJirJO'se

Hinh 7.2. Cdc loai receptor tren mang tt bao

6.1.1. Co che tac du ng cua insulin

Insulin den te bao dich n6 se giin VaG phan tho ra phia ngoai cua receptor tren mango Chinh viec giin cua hormon vdi receptor se lam thay d6i cau true phan tv receptor va lam cho phan ph an tv tho VaG ben trong te bao trd thanh kinase heat h6a. Tiep do, kinase nay se thuc dtiy su phosphoryl h6a nhieu chat khac nhau d trong te bao. H§.u het cac tac dung cua insulin tren rna dfch deu 1:\ ket qua cua cac qua trinh phosphoryl h6a nay.

6.1.2. Co che tac d urig thong qua cha't tr-uyen tin thl:i hai * Chfit truyen tin thii hai lit AMP vong

Nhieu hormon khi den te bao dfch ciing giin vdi receptor xuyen mang d(lc hieu va lam cho phan phan tv tho VaG trong te bao trd thanh enzym adenylcyclase hoat h6a.

Sau khi ducc hoat h6a, men nay Iap tire xuc tac phan ling tao ra cac phan tv cyclic 3'-5' adenosin monophophat (AMP vong) tu cac phan tv adenosin triphosphat (ATP). Phan ling nay xay ra d bao tuong. Sau khi duoc tao thanh, ngay lap tuc AMP vong hoat h6a mot chuoi cac men khac theo ki@u day truyen. Vi du men thu nhat sau khi duoc hoat h6a se heat h6a tiep men thu hai, r6i men thu hai lai hoat h6a tiep men thu ba, cu nhu the tiep tuc men thu t11, thu narn .... Vdi ki@u tac dung nhu vay, chi can mot luong rat nho hormon tac dong tren bg mat te bao dich ciing du gay ra mot dong luc hoat h6a manh cho toan te bao.

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Dap ling do AMP yang gay ra tai te bao dfch phu thucc vao cac thanh phan cau true trong te bao hay noi each khac phu thucc VaG he thong men co trong te bao dich. M9t so te bao c6 h~ thong men nay nhung mot so te bao khac lai c6 h~ thong men khac, do v~y cac tac dung duoc gay ra d te bao dich cling khong giong' nhau. Vi du khi thi xuat hien tang t6ng hop protein d te bao, khi thi lam thay d6i tinh tharn cua mang te bao, khi thi lam co hoac gian co, khi thi lam tang bai tiet dich ....

H~ thong men dap ling vdi AMP yang d te bao dich c6 th~ khac nhau giira te bao nay voi te bao khac nhung chung cung c6 met ho chung do la cac proteinkinase.

Sau khi gay ra cac tac dung sinh ly tai te bao dich, AMP yang bi bat hoat d~ trd thanh 5' AMP duoi tac dung cua men phosphodiesterase c6 trong bao tuong te bao dfch,

Nhu v~y, bang each nay hormon chi c6 mot tac dung true tiep tren mang te bao la g&n vdi receptor d~ hoat h6a men tren mang te bao chu khong tac d9ng true tiep VaG nhirng thay d6i d ben trong te bao, Chinh AMP yang gay ra tat ca cac tac dung can lai cua hormon d trong te bao, bdi v~y, nguoi ta goi AMP yang la chat truyen tin thu hai.

?roteintinase

lOngRp'p,Pr. 1Q1/g nip E 1J!lm ClJ_;gia"'n cc'

- /

gtll/ieT

Hinli 7-3. Co ehe: tdc dung thong qua AMP uong,

Cac hormon tac dung tai te bao dich thong qua AMP yang bao g6m: ACTH, TSH, LH, FSH, vasopressin, parathormon, glucagon, catecholamin, secretin, hau het cac hormon giai ph6ng cua vung dudi d6i.

* Chfit truye'n tin thit hai la ion Ca ++ va calmodulin

M9t so truong hop khi hormon hoac chat truyen dat than kinh g&n vdi receptor (protein kenh) tren mang te bao dich n6 se lam md kenh ion Ca ++ va Ca ++ diroc van chuyen VaG trong te bao.

39

Tai bao tuong, CaH giin voi mQt loai protein la calmodulin. Loai protein nay c6 4 vi tri d~ giin voi ion Ca ++.

Khi c6 3 hoac 4 vi tri giin vdi Ca ++ thi phan tv calmodulin duoc heat hoa va gay ra mot loat tac dung trong te bao tuong W tac dung cua AMP vong do la mot chuoi phan ling day truyen hoat hoa mot loat cac men xay ra (nhirng men nay khac voi men dap ling vdi AMP vong) trong te bao, M9t trong nhirng tac dung dac hieu cua calmodulin la heat hoa men myosinkinase la men tac dung true tiep len sci myosin cua co tron d~ lam co co tron.

Nong' d9 binh thuong cua ion Ca t+ trong bao tuong cua ha u het te bao la khoang 10-7 _10-8 mol/I. Nong d9 nay khong du d~ heat h6a calmodulin. Khi kenh Ca t+ md, su van chuyen Ca t+ VaG trong te bao tang len khien cho nong d9 Ca ++ tang cao toi muc 10-6 _10-5 molll va du d~ heat h6a calmodulin.

* Chilt tr uyen. tin thli hai lit ccic "nuinh+ph.osphol.ip id

M9t so hormon khi den te bao dich se giin va hoa t h6a cac receptor xuyen.mang roi heat h6a men phospholipase C la men narn d phan tho vao ben trong te bao cua phan tv receptor. Men nay lam cho cac phan tv phospholipid cua mang te baotu n6 cat thanh cac phan tv nho hen va heat dong' nhu nhirng chat truyen tin thu hai.

Nhirng hormon tac dung theo con duong nay chu yeu la cac hormon tai cha d:;ic biet la cac hormon duoc giai phong do cac phan ling mien dich va di ling.

"Manh'' phospholipid mang quan trong nhat la phosphatidyl inositol bisphosphat va cac san pham quan trong nhat co tac dung nhu nhirng chat truyen tin thu hai la inositol triphosphate va diacylglycerol.

- Inositol triphosphat huy dQng Ca ++ ttl ty lap th~ va ludi ni;)i bao tuong ra bao tuong roi sau do ion Ca t+ phat huy cac tac dung cua mot chat truyen tin thu hai nhu lam co co tron, thay d6i S1;l bai tiet ttl cac te bao che tiet, thay d6i hoat dcng' cua nhung mao.

- Diacylglycerol hoat hoa men proteinkinase C. Tac dung hoat hoa nay cang manh hen nho tac dung ho tro cua ion Ca ++ do inositol triphosphat huy dong ttl ty lap th~ va luoi nQi bao tuong. Men proteinkinase C dong vai tro dac biet quan trong trong viec thuc dfty su phan chia va tang sinh te bao.

- Them nira, thanh phan lipid cua diacylglycerol la acid arachidonic - tien chat cua prostaglandin va mot so hormon tai cha khac rna nhirng hormon tai cha nay co nhieu tac dung khac nhau d cac mo cua khap co th~.

6.2. CO CHI~ TAc Dl):\'G CUA cAc HORMO:\' GAN vor RECEPTOR TRONG TI~ BAO

Nhimg hormon co ban chat hoa hoc la steroid nhu hormon va thuong than, hormon sinh due va hormon dan xuat cua tyrosin la triiodothyronin (T3)- tetra

40

iodothyronin (T4) cua tuyen giap khi den te bao dich thi khuech tan qua mang te bao VaG ben trong te bao d~ g:1n voi receptor trong bao tuong hoac trong nhan te bao, Phuc hop hormon-receptor se heat h6a he gien, kich thich qua trinh sao chep gien d~ lam tang t6ng hop cac phan tv protein mdi d te bao dich.

6.2.1. CO CHE TAc Dl)NG CllA cAc HORMON STEROID TREN GlEN TE nAo oren HE GAy TONG HOP PROTEIN

Cac hormon vo thuong than va hormon sinh due sau khi g:1n voi receptor trong bao tuong d~ tao thanh phuc hop hormon-receptor, phuc hop nay se duoc van chuyen tu bao tuong VaG nhan te bao. Tai nhan te bao, phuc hop hormon-receptor se g:1n VaG cac vi tri dac hieu tren phan tv DNA cua nhiern s:1c th~ va hoat h6a su sao chep gien dac hieu d~ tao thanh RNA thong tin. Sa u khi ducc tao thanh, RNA thong tin se khuech tan ra bao tuong va thuc dfry qua trinh dich rna tai ribosom d~ t6ng hop cac phan tv protein maio Nhirng phan tv protein nay c6 th~ la cac phan tv enzym hoac phan tv protein van tai hoac protein diu true (Hinh 7.4).

Vi du: aldosteron la hormon cua tuyen vo thuong than ducc mau dua den te bao ang than. 'I'ai day, aldosteron khuech tan VaG bao tucng va g:1n vdi receptor. Phuc hop aldosteron-receptor se thuc dfry met chu6i cac su kien n6i tren tai te bao ang than. Sau 45 phut, cac protein van tai b:1t dau xuat hien d te bao aug than, nharn lam tang tai hap thu ion Na + va tang bai xuat ion K+.

o o o

Hinh. 7-4. Co che'tac dung thong qua hoat h6a h~ gen

Chinh vi ki~u tac dung cua hormon steroid c6 dac di~m nhu da trinh bay d tren nen tac dung thucng xuat hien cham sau vai chuc phut den vai gid, tharn chi vai ngay nhung tac dung lai keo dai, dieu nay thucng trai ngucc vci tac dung xay ra hau nhu tuc khac cua cac hormon tac dung thong qua AMP vong.

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6.2.2. Co che tac du ng cu a hormon t.uyen giap (T3-T4)

Horman T3- T4 cua tuyen giap khi duoc van chuyen den te bao dich se khuech tan VaG baa tuong rai VaG nhan te bao, TQ.i nhan te bao, hai hormon nay se g:in true tiep voi cac phan tit receptor khu tru tren cac phan tit DNA cua nhiern s:ic th~ va gay ra su sao chep gien do do heat h6a co che hinh thanh nhieu loai protein trong te bao. Cac phan tit protein nay phan Ion la cac enzyrn thuc dfry hoat dong chuyen h6a cua hiiu het cac te bao cua co th~.

Khi g:in voi receptor trong nhan te bao, T3- T4 c6 th~ duy tri tac dung heat hoa chuc nang te bao dfch trong vai ngay den vai tuan.

7. co CHE DIEU HOA llAI TIET HORMON

Cac hormon duoc bai tiet tl~eo co che digu khien tir tuyen chi huy den tuyen dich

O"'-r • ) ;

va theo co che dieu hoa ngiroc (feedback) tir tuyen dich len tuyen chi huy.

Ngoai co che. nay, S\1 bai tiet hormon can duoc digu hca theo nhip sinh h9C va chiu su tac dong cua mot so chat truyen dat than kinh (neurotransmitters).

Tuy nhien, co che dieu hoa nguoc la co che chu yeu, nhanh va nhay d~ duy tri nang dQ hormon luon hang dinh va thich ling duoc voi hoat dong cua co th~ khi song trong moi truong luon thay d6i.

7.1. mEU HOA THEO NHW SINH HOC

Nhigu hermon duoc bai tiet theo nhip gid, ngay-dern, thang, tham chi mot Quang doi.

- Hormon GH cua tuyen yen: Neu cu 30 phut lay mau mot Ian va keo dai trong 24 gid thi se thay trong ngay c6 hai thoi di~m nang dQ hormon G H cao nhfft, 2 thoi di~m do rei vao khoang 3-4 gio sau bira an.

- Hormon ACTH cua tuyen yen: Nang dQ hormon ACTH cao nhat vao luc 6-8 gio sang sau d6 giam dan va thap nhat vao hie 23 gid rai sau do Iai tang dan.

- Harmon GnRH cua vung dudi dai: Cu 3 gid duoc bai tiet mot lan, moi Ian bai tiet thuong keo dai trong vai phut.

- Hormon progesteron va estrogen cua buong trung: Vao khoang ngay 1-5 cua chu ky kinh nguyet (CKKN) nang dQ estrogen trong mau rat thap, sau do tang diin va cao nhat vao giira CKKN, sau khi ph6ng noan nang dQ hoi giam rai lai tang tiep tuc trong nita sau CKKN den khcang ngay 20-22 cua CKKN nang dQ giarn xuong dQt nget.

Cling nhu vay, trong nita diiu CKKN progesteron duoc bai tiet rat it nhung sau hien tuong ph6ng noan, progesteron duoc bai tiet voi nang dQ tang diin va cao nhat vao ngay 20- 22 cua CKKN rai sau do cling giarn dQt ngot nhu estrogen.

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- Hormon sinh due:

+ Hormon sinh due nam duoc bai tiet mot it trong thoi ky bao thai. Sau khi sinh, tuyen sinh due nam im lang cho den tu6i day thi mdi bat dau heat dong' va hoat dong lien tuc cho den cuoi doi,

+ Hormon sinh due nir duoc bai tiet k~ tu tu6i day thi va keo dai trong khoang 30 narn, sau do budng trung khong hoat dong nira va IUQng hai hormon sinh due nfi gfrn nhu bang khong.

Hi~u biet ve co che' dieu hoa bai tiet hormon theo nhip sinh h9C se giup ta danh gia chinh xac ve hoat dong va roi loan heat dong cua h~ thong noi tiet.

7.2. DIf~u H()A BANG cAc CHAT TRUYEN DA.T THAN KINH

Nhieu chat truyen dat than kinh nhu noradrenalin, dopamin, serotonin, GABA, chat P ... ngoai chuc nang d5.n truyen xung dong qua synap con tham gia dieu hoa bai tiet cac hormon nhu horrncn tuyen yen, hormon tuyen tuy n9i tiet.

Cac chat truyen dat than kinh tham gia dieu hoa chuc nang noi tiet chu yeu la cac amin nao nhu noradrenalin, doparnin, serotonin. Nhung chat nay thuong tham gia dieu hoa bai tiet hormon tuyen yen thong qua dieu hoa sinh t6ng hop, hoac bai tiet hormon giai phong va uc che cua vung dudi dai.

Dua vao co che nay, ngiroi ta d3. ling dung mot so chat truyen dat than kinh d~ dieu tri mot so benh roi IOQ.n ndi tiet.

7.3. co CHE DIEU H()A NGV9C

Co che dieu hoa nguoc Ia co che. dieu hoa chu yeu nharn duy tri hang dinh nQi moi, tao dieu kien cho cac te bao heat dong binh thuong

Trong h~ thong noi tiet, day la co che dieu hoa chu yeu, nhanh, nhay, nham duy tri su hang dinh ve nang dQ hormon.

7.3.1. Di~u hoa ng'u'oc am tinh

La kieu dieu hoa rna khi nang dQ hormon tuyen dich gram, n6 se kich thich tuyen chi huy bai tiet nhieu hormon d~ rBi hormon tuyen chi huy IQ.i kich thich tuyen dich nharn dua nang d9 tuyen dich tang trd IQ.i .muc binh thuong. Nguoc lai, khi nang dQ hormon tuyen dich tang IQ.i c6 tac dung uc che tuyen chi huy lam giam bai tiet hormon tuyen chi huy.

Vi du: Nang dQ hormon T3- T4 giarn thi ngay lap tire n6 se kich thich vung duoi dai, tuyen yen tang bai tiet TRH va TSH. Chinh hai hormon nay quay trd IQ.i kich thich tuyen g iap tang bai tiet d~ dua nang d9 T3- T 4 tro ve mire binh thuong (Hinh 7.5)

Dieu hoa ngucc am tinh la ki~u dieu hoa thuong gQ_p trong co th~ nham duy tri nang dQ hormon narn trong gidi han binh thuong.

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Vu ng du'oi deh ~ TRH

( -)

Hinh 7.5. Dieu. hoa nguac am tinh.

Roi loan co che dieu hoa nguoc am tinh se dfin den roi loan heat dong cua he thong noi tiet. Trong thuc hanh dieu tri cac benh do roi loan hoat dong cua he thong n9i tiet neu khong luu y den dac di~m nay thi c6 th~ dfin ti1 rdi loan nay sang roi loan khac, Vi du. d~ dieu tri benh nhuoc nang tuyen va thuong than (benh Addison) nguoi ta thuong dung cortisol. Neu sli dung cortisol vdi lieu luong cao va keo dai, no se gay tac dung dieu hoa nguoc am tinh len tuyen yen va lam tuyen yen giam bai tiet ACTH, hau qua la tuyen va thuong than von da hoat dong' kern nay

f

lai cang nhuoc nang hon.

7.3.2. Di~u hoa ngu'qc du'dng tinh

Khac voi ki~u dieu hoa nguoc am tmh, trong mot so truong hop nguoi ta thay ndng di? hormon tuyer; dfch tang lai c6 tac dung kich thich tuyen chi huy d~ cang lam tang hormon tuyen chi huy.

Vi du: Khi co th~ bi stress, dinh hrong nong d9 hormon thay nong d9 cortisol tang cao dong thoi n6ng d9 ACTH cling tang cao (Hinh 7.6)

Nhu vay, ki~u dieu hoa nguoc duong tinh khong nhimg khong lam 6n dinh nong d9 hormon rna nguoc lai can tang them su mat 6n dinh, Tuy nhien, S1,1 mat 6n dinh nay la can thiet nham bao v$ co th~ trong truong hop nay.

Mac du ki~u dieu hoa nguoc duong tinh trong dieu hoa hoat dong h$ noi tiet it g~p nhung lai rat can thiet bdi vi n6 thuong lien quan den nhirng hien tuong mang tinh song can cua co th~ nhu d~ chong stress, chong lanh hoac gay ph6ng noan,

44

v 0 t.huong th~n \ \ Cortisol!

Hinh 7.6. Ddu hoa nguac duang tinh (+) trong tinh trang stress

Tuy vay, ki~u dieu hoa nay thuong chi xay ra trong thoi gian ngan, sau do lai trd lai ki~u dieu hoa nguoc am tinh thong thuong. Neu keo dai tinh trang nay chic chin se d5.n den tinh trang benh 19'.

8. D~NH LUONG HORMON

Hau nhu Hit ca cac hormon d~u c6 mat trong mau vdi mot luong rat nho duoc tinh bang nanogam trong 1ml mau (10-9 g) hcac picogam/ml (10-12 g). Bdi vay, nhin chung kh6 c6 th~ dung cac ky thuat dinh luong h6a h9C thong thuong d~ dinh luong nang eti? hormon trong mau.

Tu 30 nam nay, nguoi ta da s11 dung mot ky thuat c6 d9 nhay va d9 dac hieu cao d~ dinh luong hormon, tien hormon hcac cac dan xuat cua chung, d6 la phuong phap mien dich ph6ng xa (radio immuno assay - RIA)

Ngoai phuong phap mien dich ph6ng xa (RIA) nguoi ta con dung phuong phap mien dich men (enzym immuno assay - EIA) d~ dinh luong hormon hoac dung cac phuong phap khac nhu do di? thanh thai cua hormon (metabolic clearance rate), do muc che tiet hormon.

Tuy nhien, hai phuong phap hien nay hay dung d~ dinh luong hormon la phuong phap RIA va EIA.

8.1. PHtfONG PHAp D~H LtfQNG MIEN D~CH PH6NG XA. (RIA)

8.1.1. Nguyen Hie:

Nguyen tic chung cua phuong phap dinh luong mien dich ph6ng xa la dua tren su gin canh tranh gifra hormon tv nhien (hormon trong mau can dinh luong) va

T4 - SLH

45

harmon danh dau ph6ng xa vdi khang th~ dac hieu, Mire dQ g:1n cua hai loai harmon nay vdi khang th~ ty l~ thuan voi nong dQ ban d~u cua chung. Do phuc hop harmon g:1n dong' v] ph6ng xa-khang th~ bang may dern ph6ng xa r6i dua vao duong cong chuan ta c6 th~ tinh duoc lucng harmon c6 trong dich can dinh luong.

8.1.2. Cac biroc tien hauh

- Tao khang th~ c6 tinh dac hieu cao vdi harmon can dinh luong bang each tiern

harmon tinh khiet cho mot so loai dcng vat (chuot, tho ... ).

- 'I'ron chung khang th~ vdi hai loai harmon:

Dich chua harmon can dinh luong

Horman chuan tinh khiet c6 g:1n dong vi ph6ng xa.

Digu kien d~ thuc hien duoc phuong phap dinh lucng mien dich ph6ng xa la luong khang th~ phai kh6ng du ct~ g:1n hoan toan voi ca hai loai harmon g:1n ph6ng xa va harmon can dinh luong. Khi do, tinh trang g:1n canh tranh gifia harmon c6 trong dich can dinh lucng va harmon chuan g:1n ph6ng xa vdi khang th~ se xay ra.

- Tach phuc hop harmon g:1n vdi khang th~ ra khoi phan dich con lai,

- Do phuc hop harmon g:1n ph6ng xa khang th~ bang' may dem phong xa. Neu

Iuong harmon ph6ng xa g:1n voi khang th~ nhieu thi c6 nghia la phuc hop harmon can dinh luong g:1n voi khang th~ it hay n6i each khac nong dQ harmon trong dich can dinh luong thap,

- Trang qua trmh lam 4 budc tren, song song vdi viec tien hanh tren mau dich can dinh luong, nguoi ta ciing tien hanh cac buoc tuong tv nhu tren vdi nhirng mau harmon chuan da biet truce nong dQ. Sau khi thuc hien vdi nhieu n6ng dQ khac nhau ta ve duoc duong cong chuan,

,

- Tinh luong harmon c6 trong mau dich can dinh hrorig bang each so sanh luong

phuc hop harmon ph6ng xa g:1n khang th~ dern duoc tir mau chua biet vdi duong cong chuan ve duoc tu mau da biet truce (Hinh 7.7)

Bling each nay, ta c6 th~ tinh duoc nong dQ harmon trong mau can dinh lucng voi dQ nhay c6 th~ phat hien duoc vdi lucng picogam. Sui so cua phuong phap nay vao khoang 10-15% so vdi gia tri thuc.

M9t so harmon nhu cortisol hay aldosteron cung duoc dinh luong thea phuong phap mien dich ph6ng xa nhung nguoi ta t1\udng slt dung cac globulin huyet tuong la nhirng chat thuong g:1n d~c hieu vdi cac harmon nay trong mau d~ thay the cho cac khang th~ dac hieu trong qua trinh dinh hrong. Cac budc tien hanh duoc thuc hien hoan tcan thea phuong phap RIA.

Thea nguyen ly da duoc trinh bay d tren, hien nay nguoi ta da san xuat ra cac kit RIA thuong pharn do v~y da lam don gian h6a cac budc thuc hien.

Bang' phuong phap mien dich ph6ng xa, nguoi ta c6 th~ dinh luong hang tram mau cling mot hie va cho ket qua nhanh, chinh xac.

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Hinh 7-7. Duimg cong chudn dl dinh. luang aldosteron biitig RIA

8.2. PHU'ONG PHAp "BANH K~P TH,T" ("SANDWICH")

Phuong phap nay dua tren nguyen d.c dung hai khang th~ don dong "kE?P" vao hai dau cua chat thu (harmon). M9t trong hai khang th~ duoc danh dau hoac bang dong vi phong xa hoac bang enzym. Neu goi chat can thlt la Ag, khang th~ khong danh dau la AcO, khang th~ danh dau la Ac*, ta co:

Ag + Aco + Ac* • • Aco - Ag - Ac*

Nang d9 phuc hop danh dau sau phan ling ti l~ vdi luong khang nguyen co mat. KI thuat thong dung nhat cua phuong phap nay 1a " dinh luong hap phu mien dich g:1n men" (Enzym Linked Immunosorbent Assay - ELISA).

8.3. PHU'ONG PHAp DO H(~ SO THANH THAI HORMON

Co hai yeu to lam tang hoac giarn nang dQ harmon do la toe d9 bai tiet harmon vao mau va toe d9 bai xuat harmon ra khoi mau (qua duong mat hoac qua duong nude ti~u). Toe d9 bai xuat harmon ra khoi rnau (loc sach harmon) duoc goi la h~ so thanh thai harmon (metabolic clearance rate).

D9 thanh thai harmon la so mililit huyet tuong duoc 19C sach harmon trong mot

phiit va no duoc do bang each:

Do luong harmon diroc lay khoi huye]. tuong trong mot phut (a). Do nang dQ harmon co trong mot mililit huyet tuong (b).

V~y, h~ so thanh thai harmon (C) diroc tinh thea cong thirc:

C=~ b

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VUNG DlJOI Dei!

1. D~C DIEM CAU TAO

Vung dudi d6i (hypothalmus) la mot cau true thuoc nao trung gian, nam quanh nao that ba va narn chinh gifia h~ thong vien (limbic). Vung dudi d6i co ducng lien he true tiep theo hai huang .

• Huang di len qua nhieu vung cua nao, d~c biet vung d6i thi (thalamus) truce va vung va cua h~ limbic .

• Huang di xuong qua than nao va chu yeu di den cau true ludi cua nao giira, diu nao va hanh nao.

Vung dudi d6i co nhieu noron tap trung thanh nhieu nhorn nhan va chia thanh ba vung.

- Vung duci d6i truce g6m nhirng nhorn nhan nhu nhorn nhan tren thi, nhan

canh nao that, nhan truce thi.

- Vung dudi d6i giira co nhorn nhan Wi giua, bung giira, lung giua ...

- Vung dudi d6i sau co nhorn nhan trudc vii, tren vu, cu vu .......

Cac noron cua vung dudi d6i ngoai chuc nang d§.n truyen xung dQng than kinh nhu cac noron cua cac cau true than kinh khac, con co chuc nang t6ng hop va bai tiet cac hormon.

Vung duoi d6i co moi lien h~ mat thiet qua ducng mach mau va ducng than kinh vci tuyen yen (se duoc trtnh bay a bai Tuyen yen). Cac hormon do vung duoi d6i bai tiet se theo nhirng con ducng nay den du tru hoac tac dQng (kich thich hoac uc che) den chuc nang cua tuyen yen.

2. CAC HORMON GIAI PH6NG VA trc CHE CVA VUNG OUCH DOl

Cac noron cua vung dudi d6i rna than cua chung co th~ nam a cac nhorn nhan khac nhau cua vung dudi d6i va tan cung cua noron thi khu trii tai vung 16i giira co kha nang t6ng hop cac hormon giai phong (releasing hormone) va cac hormon uc che' (inhibitory hormone) d~ kich thfch hoac uc che' hoat dQng cua cac te bao thuy truce tuyen yen.

Cac hormon giai phong va uc che. sau khi duoc t6ng hop tu than noron, chung duoc van chuyen theo sci true xuong tich tru d cac tui nho trong tan cung than kinh narn d vung 16i giira. Tai day, hormon khuech tan VaG mang mao mach thu nhat r6i theo he mach cua duoi d6i-yen xuong thuy trudc tuyen yen.

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2.1. BAN CHAT HOA HOC vA TAc Dl)NG CllA cAc HORMON GIAI PHONG vA rrc CHE

• Hormon giai phong va uc che GH- GHRH va GHIH (Growth Hormone Releasing Hormone va Growth Hormone Inhibitory Hormone):

Ca hai deu la polypeptid co 44 acid amino

Tyr- Ala- Asp- Ala- Ile- Phe- Thr- Arn- Ser- Tyr- Arg- Lys- Val- Leu- GlyGln- Leu- Ser- Ala- Arg- Lys- Leu- Leu- Gln- Asp- Ile- Met- Ser- Arg- Gln- GlnGly- Gla- Ser- Asn- Gln- Glu- Arg- Gly- Ala- Arg- Ala- Arg- Leu- NH2

G HRH do cac noron cua nhorn nhan bung giira bai tiet, Day la vung rat nhay cam vdi su giarn nang dQ glucose trong mau va gay ra cam giac doi,

GHRH khi den thuy truce tuyen yen sau khi g:in voi receptor cua mang te bao thi heat hoa adenylcyclase rai tao AMP vong. AMP vong se gay ra nhirng thay d6i tire thi va nhirng thay d6i keo dai trong bao tuong te bao dich.

Tac dung tire thi la lam tang van chuyen ion Ca ++ vao trong te bao, chinh ion Ca ++ co tac dung d5y cac tui chua GH sat vao mang te bao rai hoa mang va giai phong GH vao mau tuan hoan,

'I'ac dung keo dai do GHRH gay ra do la lam tang su sao chep gien trong nhan te

bao ua acid d thuy truce tuyen yen d~ lam tang t6ng hop GH .

• Hormon giai phong TSH - TRH (Thyrotropin Releasing Hormone).

TRH la hormon co cau true rat don gian, chi gam 3 acid amin (Glu- his- pro). TRH do cac tan cung than kinh d vung 16i giiia bai tiet vao he mach cira duoi

d6i- yen. Than cua nhimg noron t6ng hop TRH nam d nhorn nhan nao hien nay van chua biet ro. Tuy nhien, khi tiern khang th~ dac hieu danh dau nguoi ta thay TRH co mat d nhieu vung nhu nhorn nhan lung giua, bung giira, vung duoi dai truce, trudc thi, canh nao that, tren cheo thi.

TRH kich thich true tiep te bao thuy truce tuyen yen t6ng hop va bai tiet TSH.

T6n thucng h~ thong cira dan tu vung dudi d6i den tuyen yen lam cho muc bai tiet TSH co th~ giarn tdi rmrc bang kh6ng.

Co che tac dung cua TRH tai te bao tuyen yen la sau khi g:in voi receptor thi hoat hoa men phospholipase cua mang te bao bai tiet TSH d~ san xuat mot luong ldn phospholipase C. Tiep theo do la cac su kien khac xay ra nhu ion Ca ++ duoc van chuyen vao trong te bao va tao thanh diacyl glycerol.

• Hormon giai phong ACTH - CRH (Corticotropin Releasing Hormone) CRH la mot polypeptid co 41 acid amino

49

Ser- Glu- Glu- Pro- Pro- Ile- Ser- Leu- Asp- Leu- Thr- Phe- His- Leu- LeuArg- Glu- Val- Leu- Glu- Met- Ala- Arg- Ala- Glu- Gln- Leu- Ala- Gln- G1n- AlaHis- Ser- Asn- Arg- Lys- Leu- Met- Glu- Ile- Ile- NH2

CRH do cac tan cung than kinh d vung 16i gifia rna than cua cluing chu yeu narn d nhan canh nao that bai tiet vao he cira dudi doi-yen. Nh6m nhan nay nhan nhieu m6i lien h~ than kinh tU h~ limbic va cuong nao dudi.

CRH c6 tac dung kich thich thuy truce tuyen yen t<5ng hop va bai tie't ACTH.

Vang' mat CRH, tuyen yen chi bai tie't mot hrcng rat it ACTH. Trong hau he't cac truong hop gay bai tie't mot luong Ion ACTH thi cac tin hieu kich thich dgu duoc xuat phat tu cac vung nen nao bao g6m vung diroi d6i r6i tin hieu do duoc chuyen xuong tuyen yen thong qua CRH.

• Hormon giai ph6ng FSH va LH - GnRH (Gonadotropin Releasing Hormone). GnRH la mot peptid c6 10 acid amino

pG1u- His- Trp- Ser- Tyr- Gly- Leu- Arg- Pro- Gly- NH2.

GnRH duoc bai tiet tU cac tan cung than kinh narn d vung 16i giira, than cua nhirng noron nay khu tru d nhan cung (arcuate nuclei) cua vung dudi d6i.

GnRH duoc bai tie't theo nhip, cir 1-3 gid GnRH duoc bai tiet mot lan, m6i Ian thoi gian bai tie't keo dai trong vai phut.

Tac dung cua GnRH la kich thich te' bao thuy trudc tuyen yen bai tie't ca FSH va LH. Tuy nhien, nhip bai tie't LH lien quan chat che vdi nhip bai tie't GnRH hon la FSH. C6 Ie chinh vi Ii do nay rna nhieu khi nguoi ta goi GnRH la LHRH. Viing mat GnRH hoac neu dua GnRH lien tuc vao mau den tuyen yen thi ca. FSH va LH dgu khong duoc bai tie't.

• Hormon lic che' prolactin - PIH (Prolactin Inhibitory Hormone2c Cau true h6a h9C cua PIH den nay v§.n chua ro.

Tac dung cua PIH la uc che' bai tie't prolactin tu te' bao thuy truce tuyen yen.

2.2. DIEU HOA BAI TIth cAc HORMON GIAI PH6NG vA (rc cHE

Cling nhu cac hormon khac trong h~ n9i tiet, cac hormon giai ph6ng va uc che' duoc dieu hoa chu yeu bing co che' dieu hoa nguoc rna cac tin hieu dieu hoa xuat phat tu tuyen yen hoac cac tuyen ngoai bien khac (Hinh 7- 8).

* Co che' dieu hoa nguoc do cac hormon tuyen dich ngoai bien dieu khien (tuyen giap, tuyen vo thuong than, tuyen sinh due) duoc goi la co che dieu hoa nguoc yang dai.

* Co che' digu hoa nguoc do cac hormon tuyen yen dieu khien (GH, TSH, ACTH, FSH, LH, Prolactin) duoc goi la co che dieu hoa nguoc yang ngan.

50

'* Co che dieu hoa nguoc do chinh ndng dQ harmon cua vung duoi d<3i dieu khi~n duoc goi la co che dieu hoa nguoc vong cue ngan. Co che nay mdi chi Urn thay d hai harmon GnRH va TRH.

Tuyen g'iap T3- T4

1. Dieu hoa nguoc vong dai,

2. Dieu hoa nguoc vong ngan

3. Dieu hoa nguoc vong cue ngan

Hinli 7-8. IJie'u hoa bai tie/; hormoti uung dudi a6L

3. cAc HORMON KHAc

Ngoai cac harmon giai phong va uc che, cac noron thuoc hai nhom nhan tren thi va canh nao that can t6ng hop hai harmon khac la ADH (vasopressin) va oxytocin. Hai harmon nay duoc t6ng hop d than te baa r<3i thea soi true den tich tru d thuy sau tuyen yen.

Ban chat hoa h9C, tac dung va dieu hoa bai tiet hai harmon nay se duoc trinh bay d phan cac harmon thuy sau tuyen yen (xem bai Tuyen yen).

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TUYENYEN

1. D~C DIEM cKu T 1\0 V A MOl LIEN Hi!: VOl VUNG DUOI DOl

1.1. V. TRI V A MOl LIEN H~ VOl VUNG DUOI DOl

Tuyen yen Ia mot tuyen nho duong kinh khoang 1 em, nang tU 0,5 - 19. Tuyen yen narn trong ho yen cua xuong budm thuoc nen S9.

Tuyen yen g6m hai phan c6 nguon goc cau tao tU thoi ky bao thai hoan toan khac nhau do la thuy trudc va thuy sau (Hinh 7.9).

Tuyen yen lien quan mat thiet voi vung dudi d6i qua duong mach mau va duong than kinh do la h~ thong cira d udi d6i - yen va b6 soi than kinh d udi d6i - yen.

1. Vung dudi d6i 3. Thuy trudc

5. Thuy giira

2. Cuong yen 4. Thuy sau

Hinh 7-9. Tuysn. yen

- H~ thong cua dudi doi- yen (he cua Popa-Fielding) duoc cau tao bdi mang mao mach thu nhat xuat ph at tU dong mach yen tren. Mang mao mach nay toa ra d vung 16i giiia (Median Eminence) r6i tap trung thanh nhirng tinh mach cira dai di qua cuong tuyen yen r6i xuong thuy trudc tuyen yen toa thanh mang mao mach thu hai

52

cung cap 90% luong mau cho thuy triroc tuyen yen. LUQng mau con lai la tu cac tinh mach cua ngan biit dau tu mang mao mach cua dong mach yen dudi (Hinh 7.10).

Cac hormon giai ph6ng va uc che cua vung dudi d6i duoc bai tiet chu yeu tu cac tan cung cua noron vung 15i gifia se tharn VaG mang mao mach 16i giua r6i theo h~ thong cua dudi d6i - yen xuong dieu khi~n su bai tiet hormon cua tuyen yen.

- B6 soi than kinh dudi d6i - yen la b6 than kinh g5m cac soi true cua cac noron rna than narn d hai nh6m nhan tren thi va canh nao that con tan cung cua chung thi khu trii d thuy sau tuyen yen (Hinh 7.10).

NTill

10

1,2,3,4,5: Than noron cua VDD 6: Vung duoi d5i

7: Dong mach yen tren 8: Tinh mach cua dai

9: Tinh mach cira ngan 10: Dong mach yen dudi

Hinh 7.10 MOL lien h~ giita VDn - Tuyen. yen

Hai hormon do cac noron cua nh6m nhan tren thi va canh nao that t6ng hop va bai tiet se theo b6 soi than kinh nay den du trfi d thuy sau tuyen yen do vay cac tin

53

j

hieu kich thich VaG vung duoi d6i hoac thuy sau tuyen yen deu gay bai tiet hai

hormon nay.

Neu tach roi mdi lien he giira thuy sau tuyen yen va vung duoi d6i bang mot nhat cat qua cuong tuyen yen (cat phia tren tuyen yen) thi hormon thuy sau tuyen yen giarn thoang qua trong vai ngay r6i trd lai binh thuong. Nong dQ hormon thuy sau tuyen yen trd lai blnh thuong khong phai do cac tan cling than kinh narn d thuy sau tuyen yen bai tiet rna la do cac dau bi cat roi narn d vung dudi d6i bai tiet vi nhirng hormon nay duoc t6ng hop d than noron cua nhan tren thi va nhan canh nao that sau d6 duoc chuyen theo sci true den cac cue tan cling khu tru d thuy sau tuyen yen. Qua trinh di chuyen nay doi hoi vai ngay.

1.2. D~e DIEM eAu T;).O eVA TUYEN YEN 1.2.1. 'I'huy tru'oc t.uyen ye n (t.huy t.uyen)

Thuy trudc tuyen yen duoc cau tao bdi nhirng te bao che' tiet. Nhirng te bao nay c6 nhieu loai, moi loai t6ng hop va bai tiet mot loai hormon.

Khoang 30-40% te bao tuyen yen bai tiet hormon GH, nhirng te bao nay khi nhuom chung bat mau acid manh nen can duoc goi la te bao ua acid.

Khoang 20% te bao tuyen yen la nhirng te bao t6ng hop va bai tiet ACTH.

Cac te bao t6ng hop va bai tiet cac hormon khac cua thuy truce tuyen yen moi loai chi chiern tu 3-5% nhung chung c6 kha nang bai tiet hormon rat manh d~ dieu hoa chirc nang tuyen giap, tuyen sinh due va tuyen vu.

1.2.2. 'I'huy sau t.uyen yen (t.huy th~', kinh)

Thuy sau tuyen yen duoc cau tao chu yeu bdi cac te bao giong' te bao than kinh dern (glial like cell). Nhirng te bao nay khong c6 kha riang che tiet hormon rna chi lam chirc nang nhu met cau true ho tro cho mot luong ldn cac sci true va cue tan cling sci true khu tru d thuy sau tuyen yen rna than narn d nhan tren thi va nhan canh nao that. Trong cue tan cling cua nhfmg sci than kinh nay c6 cac tui chua hai hormon la ADH va oxytocin.

2. eAe HORMON THUY TRUde TUYEN YEN

Thuy truce tuyen yen t6ng hop va bai tiet 6 hormon d6 la:

- Hormon ph at tri~n co th~ - GH (Human Growth Hormone - hGH)

- Hormon kich thich tuyen giap - TSH (Thyroid Stimulating Hormon)

- Hormon kich thfch tuyen vo thirong th~l( - ACTH (Adreno Corticotropin Hormon).

- Hormon kich thich nang trung - FSH (Follicle Stimulating Hormon)

- Hormon kich thich hoang th~ - LH (Luteinizing Hormon)

- Hormon kich thich bai tiet sira - PRL (Prolactin).

54

Ngoai tru GH la horrnon c6 tac dung dieu hoa true tiep chuc nang chuyon h6a cua toan bQ cd th~, cac horrnon can lai chi tac dung dac hieu len mot tuyen hoac mot rna nao do, va thong qua tac dung len cac tuyen noi tiet nay d~ dieu hoa cac chirc nang chuyen h6a cua cd th~ nhu horrnon TSH, ACTH, FSH, LH va PRL.

2.1. HORMON PH AT TRIEN co THE- GH (hGH)

2.1.1. Ban chat hoa hoc

GH la mot phan tit protein nho chua 191 acid arnin trong mot chuoi don va c6 trong luong phan tit la 22.005.

2.1.2. Tilc du ng

GH gay ph at tri~n hau het nhfing rna c6 kha nang ta~g trudng trong co th~. N6 vua lam tang kich thuoc te bao vua lam tang qua trinh ph an chia te bao dodo lam tang trong luong cd th~, lam tang kich thuoc cac phu tang.

Kfch thich rna sun va xuong ph at trien,

- Nhu tren da trinh bay, GH c6 tac dung phat trien hau het cac rna cua cd th~ trong do hieu qua thay r6 nhat la lam ph at tri~n khung xuong. Ket qua nay la do anh hucng cua GH len xuong nhu:

+ Tang ling dong protein d cac te bao sun va te bao tao xuong. + Tang toe dQ sinh san cac te bao sun va te bao tao xuong.

+ Tang chuyen cac te bao sun thanh cac te bao tao xuong.

- GH lam xuong phat tri~n nho hai cd che chinh:

+ Co che lam dai xuong: GH lam ph at tri~n sun d dau xuong dai, nci rna dau xuong tach khoi than xuong. S1;l phat tri~n nay bit d§.u bang' tang phat tri~n rna sun, sau do rna sun se duoc chuyen thanh rna xuong mdi do do than xuong se dai ra r6i rna sun mdi lai ducc tao thanh. Dong thoi vdi viec pha t tri~n rna sun thi rna sun tu n6 cung din dan duoc cot h6a sao cho den tu6i vi thanh nien (adolescence) thi rna sun d d§.u xuong khong can nira, hie nay d§.u xuong va than xuong se hop nhat lai voi nhau va xuong khong dai ra nira.

Nhu v~y, GH kich thich ca S1;l ph at tri~n rna sun diu xuong va chieu dai xuong nhung khi rna d§.u xuong hop nhat vdi than xuong thi GH khong can kha nang lam dai xuong nira.

+ Co che lam day xuong: Trong xuong c6 hai loai te bao c6 tac dung nguoc nhau, do la te bao tao xuong va te bao huy xuong. Te bao tao xuong thuong narn d tren be mat xuong va trong mot so hoc xuong. Te bao nay c6 tac dung tang ling dong cac hop chat calci va phosphat mdi tren be mat cua xuong cu. D6ng thdi,'te bao huy xuong lai tiet ra nhfmg chat nharn hoa tan cac hop chat calci va phosphat va lam pha huy rna xucng. Khi rmrc ling dong tang hen mire pha huy thi chieu day xuong tang len.

55

Hormon GH co tac dung kich thich manh te' bao tao xuong, do v~y xuong tiep tuc day ra dudi anh huong cua GH, d:\ic biet la mang xuong. T'ac dung nay duoc th~ hien ngay ca khi co th~ d5. truong thanh d:\ic biet doi vdi cac xuong det nhu xuong ham, xuong SQ, va nhirng xuong nho nhu xuong ban tay va xuong ban chan. Khi GH duoc tie't ra qua nhieu d nhirng nguoi da truong thanh thi xuong ham day len va dfry dim nho ra, xuong so cling day len lam cho dau to ra, xuong ban chan hay ban tay cling day len lam ban chan ban tay to ra.

- GH tac dung thong qua chat trung gian la somatomedin hay con goi la yeu to phat tri~n giong insulin (insulin like growth).

Tu thf nghiern tren dong vat, ngtroi ta tim thay GH kich thich gan tao ra nhieu phan tv protein duoc goi la somatomedin, chat nay gay ra cac tac dung tren xuong. Nhi~u tac dung cua somatomedin len su phat trien giong tac dung cua insulin nen no con co ten la "chat lam phat tri~n giong insulin" (IGF).

Ngudi ta da chiet tach duoc bon loai somatomedin trong do loai quan trong nhat la somatomedin C (duoc goi la IGF -1). Trong lUQug phan tv cua somatomedin C VaG khoang 7500 va ncng d9 cua n6 thuong ty l~ voi muc bai tiet GH. a nhung nguoi lun pygmy nong d9 somatomedin trong huyet tuong thuong thap ngay ca khi ndng d9 GH binh thuong hoac cao.

Bdi vay, nguoi ta cho ding tat ca hcac hau nhu tat ca cac tac dung cua GH len su phat trien co th~ chinh la do tac dung cua somatomedin C va cac somatomedin khac chu khong phai la tac dung true tiep cua GH tren xuong hoac cac rna khac.

Tuy nhien, mot so y kien khac lai cho ding c6 th~ G H kich thfch su tao thanh met luong somatomedin C du d mot rna nao do d~ lam rna nay phat tri~n nhung cling c6 th~ GH tu n6 c6 tac dung true tiep lam phat tri~n mot so rna khac va tac dung thong qua somatomedin chi la mot trong nhimg each lam phat trien co th~ cua GH chu khong phai la mot co che' duy nhat.

• Kich thich sinh t6ng hop protein.

G H c6 nhieu tac dung len chuyen h6a protein, nhimg tac dung nay dan den tang protein cua te bao.

- Tang van chuyen acid amin qua rnang te bao: GH lam tang true tiep toc d9 van chuyen acid amin tU mau vao trong te bao. Su tang nong d9 acid amin trong te bao se dan den tang t6ng hop protein. 'I'ac dung tang van chuyen acid amin qua mang te bao cua GH cling gicng nhu tac dung tang van chuyen glucose qua mang te bao cua insulin do tuyen tVY n9i tiet bai tiet.

- Tang qua trinh dich rna RNA d~ lam tang t6ng hop protein tU ribosome. Ngay ca khi nong di? acid amin trong te bao khong tang thi G H cling lam tang dich rna RNA d~ lam tang so luong phan tv protein duoc t6ng hop tu ribosome d bao tuong cua te bao.

56

- Tang qua trinh sao chep DNA cua nhan te bao d~ tao RNA: Tac dung cham hon (tu 24 gid - 48 gio) cua GH la kich thich su sao chep DNA trong nhan d~ tao RNA. RNA se thuc dlly su sinh t6ng hop protein, thuc dlly su phat trien neu duoc cung cap du nang luong, acid amin, vitamin va cac yeu to khac din cho su ph at trien.

C61e day la tac dung quan trong nhat trong cac tac dung cua GH. - Giarn qua trinh thoai h6a protein va acid amino

• Tang tao nang luong tU nguon lipid.

- GH c6 tac dung tang giai ph6ng acid beo tU cac rna rna du trfi, do do lam tang nong dQ acid beo trong mau.

- 0 rna, n6 lam tang chuyen acid beo thanh acetyl-CoA r6i S11 dung cho muc dich sinh nang luong. Do vay, duoi tac dung cua GH, lipid duoc S11 dung d~ tao nang luong nhieu hon la glucid va protein.

.

- Chfnh vi tac dung nay rna nguoi ta coi tac dung huy dQng lipid cua GH la mot

trong nhung tac dung quan trong nhat nharn tiet kiern protein d~ dung n6 cho su phat tri~n co th~.

Tuy nhien, tac dung tren chuyen h6a lipid thuong xay ra cham sau vai gid trong khi tac dung lam tang sinh t6ng hop protein c6 th~ xuat hien sau vai phut dudi tac dung cua GH.

• Tac dung tren chuyen h6a glucid .

GH c6 bon tac dung tren chuyen h6a glucid , do la lam giarn S11 dung glucose cho muc dich sinh nang luong, tang du trfi glycogen d te,bao, giarn dua glucose vao te bao, tang bai tiet insulin va giarn tinh nhay cam vdi insulin.

- Giarn S11 dung glucose cho muc dich sinh nang luong.

Co che chinh xac gay ra su giarn tieu thu glucose d te bao dudi tac dung cua GH den nay van chua ro. Tuy nhien, nguoi ta cho rling tac dung nay c6 Ie mot phan la do GH tang huy dQng va S11 dung acid beo d~ tao nang luong. Chfnh tac dung nay da lam tang ncng dQ acetyl-CoA, sau d6 acetyl-CoA c6 tac dung dieu hoa nguoc d~ uc che qua trinh thoai h6a glucose va glycogen.

- Tang du trfi glycogen d te bao: Khi n6ng dQ GH tang, glucose va glycogen khong th~ thoai h6a d~ sinh nang luong, glucose duoc van chuyen vao te bao se trung hop thanh glycogen do do te bao nhanh ch6ng bi bao hoa glycogen den mire khong th~ du tru them duoc nira.

- Giarn van chuyen glucose vao te bao va tang ndng dQ glucose trong mau.

Khi tiern GH cho dong vat thay hie dau glucose duoc van chuyen vao te bao tang len va ncng dQ glucose trong mau giarn nhe nhung tac dung nay chi keo dai khoang

57

30 phut den 1 gid r6i sau do tac dung xay ra nguoc 19-i nghia la su van chuyen glucose VaG te bao giarn. Tac dung nay xay ra c6 Ie do te bao kh6 s1'1 dung glucose nen nong d9 glucose trong te bao tang len da lam giarn van chuyen glucose VaG te bao,

Do su s1'1 dung glucose trong te bao giarn nen nong d9 glucose trong mau tang tdi 50% hoac hon, tinh trang nay duoc goi la dai thao duong tuyen yen. Truong hop nay neu dieu tri bang insulin thuong phai dung mot IUQng Ion insulin mdi c6 th~ lam giarn nong d9 glucose trong mau, vi vay dai thao duong 109-i nay it nhay cam vdi insulin.

- Tang bai tiet insulin.

Nong d9 glucose trong mau tang duoi tac dung cua GH da kich thich tuyen tuy n9i tiet bai tiet insulin, d6ng thoi chinh GH cung c6 tac dung kich thich true tiep len te bao beta cua tuyen tuy, D6i khi ca hai tac dung nay gay kfch thich qua manh den te bao beta lam chung bi t6n thuong va se gay ra benh dai thao duong tuy. Do vay, GH la hormon c6 tac dung gay dai thao duong.

2.1.3. Ba i tiet va v;;tn chuytin GH trong mall

Nong d9 GH trong mau tre con khoang 6 ng/ml, d nguoi truong thanh la tir 1,6 - 3 ng/rnl. Su bai tiet GH giarn d nguoi cao tu6i nhung cling chi giarn khoang 25% so vdi tu6i vi thanh nien,

Nong d9 GH c6 th~ tang cao tdi 50 ng/ml khi suy giarn du kG' protein hoac carbohydrat cua co th~ do tinh trang suy dinh dudng keo dai, Trong tinh trang cap tinh, su giarn nong d9 glucose trong mau kich thich bai tiet GH manh hen so vdi su giarn nong d9 protein. Nguoc 19-i, trong tinh trang man tinh thi su bai tiet GH 19-i chiu anh hucng cua su thieu protein hen la su thieu glucose.

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2- Ngll say Hinh 7-11. Bdi tiel GH

58

o nguoi Vi~t Nam, nong dQ GH trong mau cuong ron tre so sinh la 28,38 ± 10,03 ng/ml, ngiroi truong thanh la 3,94 ± 2,09 ng/ml (Mai Trong Khoa va CS, 1995).

Trong mau, GH chi g<1n long leo vdi protein huyet tuong nen giai ph6ng rilt nhanh VaG mau. Thoi gian ban huy cua GH thuong dudi 20 phut trong khi do thoi gian ban huy cua somatomedin khoang 20 gic.

Ne'u cu 30 phut lily mau mot l§.n d~ dinh luong dien bien nong dQ GH trong 24 gio thi thay ban ngay c6 hai thoi di~m nong dQ GH cao nhat, hai thoi di~m nay thuong each sau bira an khoang 3-4 gio, Ban dern hai gio dau khi ngu say nong dQ GH cling rat cao r6i sau d6 giarn dan ve sang (Hinh 7.11). Khi tap luyen hoac lao dong' nang thi GH cling duoc bai tiet nhieu

2.1.4. Di~u hoa bai tiet

• Vung dudi d6i: GH duoc bai tiet dudi sir dieu khi~n h§.u nhu hoan toan cua hai hormon vung duoi d6i la GHRH va GHIH (xem bai Vung dudi doi).

• Somatostatin la mot hormon tai ch6 do nhieu vung nao va duong tieu h6a bai tiet (xem bai hormon tai ch6) cling c6 tac dung uc che bai tiet GH.

• Nong dQ glucose trong mau giarn, nong dQ acid beo trong mau giarn, thieu protein nang va keo dai se lam tang bai tiet GH.

• 'I'inh trang stress, chan thuong, luyen tap g<1ng sire se lam tang bai tiet GH.

2.2. HORMON KICH THICH TUYEN GIA.p TSH

2.2.1. Ban chat hoa hoc

,

TSH la mot glycoprotein, c6 trong hrong phan tv 28.000.

2.2.2. Tilc d urig

- Tac dung len cau true tuyen giap,

• Tang so hrcng va kich thudc te bao tuyen giap trong m6i nang giap.

• Tang bien d6i cac te bao nang giap tit dang khoi sang dang tru (dang bai tiet),

• Tang phat tri~n h~ thong mao mach cua tuyen giap, - Tac dung len chirc nang tuyen giap,

• Tang hoat dQng born iod do d6 lam tang kha nang b<1t iod cua te' bao tuyen giap. D6i khi lam cho ty l~ iod giira trong te bao giap va ngoai te bao tang gilp 8 Ian so voi binh thuong.

• Tang g<1n iod VaG tyrosin d~ tao hormon tuyen giap.

• Tang ph an giai thyroglobulin duoc du tril trong long nang giap d~ giai ph6ng hormon tuyen giap VaG mau va do d6 lam giarn chat keo trong long nang giap.

59

2.2.3. Di~u hoa hili tiet

Muc bai tiet TSH cua tuyen yen chiu su dieu khien cua tu tren xuong cua hormon TRH vung dudi dai va chiu su dieu hoa nguoc tU tuyen dich 1£1 tuyen giap.

o nguoi Vi~t nam binh thuong nang dQ TSH d tre so sinh (mau cuong ron) 1£1 6,24 ± 2,69 va nguoi truong thanh (16-60 tu6i) 1£1 2,12 ± 0,91 mUll (Phan Van Duyet va CS, 1995).

• Neu nang dQ TRH cua vung dudi dai tang thi tuyen yen se bai tiet nhieu TSH va nguoc lai neu TRH giarn thi nong dQ TSH giarn. Khi h~ thong cua duoi dai- yen bi t6n thuong, mire bai tiet TSH cua tuyen yen c6 th~ giarn tdi muc bang khong.

• Nang dQ hormon tuyen giap anh huong den su bai tiet TSH cua tuyen yen theo co che' dieu hoa nguoc am tinh va duong tinh (xem bai Dai cuong ve he ndi tiet va hormon).

2.3. HORMON KICH THICH TUYEN VO THV<)NG TH~N - ACTH

2.3.1. Ban cha't hoa hoc

ACTH 1£1 mot phan tli polypeptid Ion g6m 39 acid amin, chuoi polypeptid nho hon dU'c;JC tach tu ph an tli ACTH chi gam 24 acid amin nhung cling c6 tat ca cac tac dung nhu cua ACTH.

2.3.2. Tac d u ng

• Tac dung len cau true tuyen vo thuong than.

ACTH lam tang sinh te bao tuyen vo thuong than dac biet 1£1 te bao cua lop b6 va ludi 1£1 nhirng te bao bai tiet cortisol va androgen do d6 lam tuyen nd to. Thieu ACTH tuyen vo thuong than se bi teo lai.

• Tac dung len chuc nang vo thuong than.

ACTH den tuyen vo thuong than se g<1n vdi receptor tren mang te baa va hoat h6a men adenyl cyclase rai gay ra su hinh thanh AMP vong d rmrc toi da chi sau 3 phut. Tac dung quan trong nhat cua cac budc xay ra trong bao tuong duoi kich thich cua ACTH la dieu hoa su bai tiet hormon vo thuong than do hoat h6a men proteinkinase A. Chinh men nay sau khi duoc hoat hoa se thuc diiy phan ung chuyen cholesterol thanh pregnenolon - 1£1 chang dflu tien cua qua trinh sinh t6ng hop cac hormon vo thuong than.

• Tac dung len nao.

- Tiern ACTH VaG nao chuot thay nh6m chuot nay tim duoc loi di moi d~ tranh loi di c6 nguy hi~m nhanh hon 16 chuot chung. Tu thi nghiern nay nguoi ta cho rang ACTH c6 vai tro lam tang qua trlnh h9C tap va tri nhd.

- Tiern ACTH VaG nao lam tang su so hai d mdt so dQng vat, tU d6 nguoi ta cho rang ACTH co Ie c6 su lien quan vdi su so hai,

60

• Tac dung len te bao sac to.

Do trong 39 acid amin cua chuoi polypeptid cua phan tv ACTH c6 13 acid amin giong chuoi a MSH nen ACTH c6 tac dung gidng tac dung cua MSH.

Tren mot so loai d9ng vat cap thap nhu ech, nhai, ca, luong MSH duoc bai tiet nhieu ttl thuy giua cua tuyen yen. MSH c6 tac dung phan tan cac hat s~c to tren be mat cua te bao bi~u bi da lam cho da nhirng dong vat nay c6 mau sam.

o nguoi, thuy giiia teo nho, lucng MSH duoc bai tiet kh6ng dang k~ va tac dung cua MSH do ACTH dam nhan. Chinh ACTH co tac dung kich thich te bao sac to san xuat s~c to melanin r6i phan tan s~c to nay tren be mat bi~u bi da. Thieu ACTH se lam cho da kh6ng co sac to (nguoi bach tang). Nguoc lai thua ACTH lam cho tren da c6 nhirng mang s:ic to.

2.3.3. Di~u hoa bili tiet

• Do n6ng d9 CRH cua vung dudi d6i quyet dinh, khi nong d9 CRH tang thi ACTH duoc bai tiet nhieu nguoc lai khi vang mat CRH, tuyen yen chi bai tiet mot luong rat it ACTH.

• Do tac dung dieu hoa nguoc am tinh va duong tinh cua cortisol (xem bai Dai cuong ve h~ noi tiet va hormon).

__ Cod/sol

X--x ACTf1

(ng/tlt)

16

12

8

4-

O~~r--*~~-rL-.---~--.---,---~~~--~--

eh 911

Thi: t1iej" lay mall

( A!gjtlt)

25

2.0

15 10

o

Hinh 7-12. Nhip bai titt ACTH va cortisol d nguai binh thuang bu6i sang sdrri

T5 - SLH

61

Nang d9 ACTH can duoc dieu hoa theo nhip sinh h9C. Trong ngay, nang d9 ACTH cao nhat vao khoang tU 6-8 gio sang sau do giarn dan va thap nhat VaG khoang 23 gio rai lai tang dan ve sang (Hinh 7-12).

Binh thuong nang d9 ACTH trong huyet tuong VaG bu6i sang khoang 10-50 pg/ml khi bi stress nang d9 tang rat cao c6 thti len tdi 600 pg/ml. 6 nguoi Viet N am trucng thanh (lay mau hie 8h30 sang tren 25 nam khoe manh) nang d9 ACTH la 9,7773 ± 4,599pg/ml (Pharn Thi Minh Duc va CS, 1998).

2.4. HORMON KicH THicH TUYEN SINH Dl)C: FSH vA LH 2.4.1. Ban chat hoa h9C

Ca FSH va LH deu la glycoprotein. LUQng carbonhydrat g:1n vdi protein trong phan tv FSH va LH thay d6i trong nhirng dieu kien khac nhau va khi do hoat tinh cua chung cung thay d6i.

FSH duoc cau tao bdi 236 acid amin vdi trong luong phan tv 32.000, can LH c6

215 acid amin va trong lucng phan tv la 30.000.

2.4.2. Tac du ng

- T'ac dung tren tuyen sinh due narn (tinh hoan). +FSH

• Kich thich orig sinh tinh pha t trien.

• Kich thich te bao Sertoli narn d thanh ang sinh tinh phat trien va bai tiet cac chat tham gia vao qua trinh san sinh tinh trung. Neu khong c6 tac dung kich thich nay tinh tv se khong thti trd thanh tinh trung duoc. Tuy nhien trong qua trinh sinh san tinh trung, ngoai FSH can c6 vai tro cua hormon khac dac biet la testosteron.

+LH

t

• Kich thich te bao ke Leydig (narn giira cac ang sinh tinh) phat trien, Binh

thuong te bao ke Leydig truong thanh kh6ng duoc tim thay (j tinh hoan cua tre duoi 10 tu6i. Tuy nhien neu tiern LH tinh khiet cho tre hoac duoi tac dung cua LH d tu6i day thi, cac te bao giong nhu nguyen bao sci narn d vung ke cua tinh hoan se tien h6a tha~h te bao Leydig.

• Kich thfch te bao ke Leydig bai tiet testosteron. - T'ac dung tren tuyen sinh due rrir (buong trung), +FSH

• Kich thich cac noan nang pha t tritin dac biet la kich thich tang sinh ldp te bao hat dti tu do tao thanh ldp vo (lop ao) cua nang trirng.

+LH

• Phoi hop vdi FSH lam phat tritin noan nang tien tdi chin.

• Phoi hop vdi FSH gay hien tuong ph6ng noan.

• Kich thich nhirng te bao hat va lop vo can lai phat tritin thanh hoang thti.

• Kich thich lop te bao hat cua nang trung va hoang thti bai tiet estrogen va progesteron.

62

2.4.3. S1;i bai tiet FSH va LH

Hai hormon FSH va LH chi b~t dffu duoc bai tiet tU tuyen yen cua tre em d hra tu6i 9-10 tu6i. Luong bai tiet hai hormon nay tang dan va co rmrc cao nhat vao tu6i day thi,

Binh thuong nong dQ FSH va LH d ill1' giao dong trong chu ky kinh nguyet (CKKN) can d nam gidi thi khong thay hien tuong nay. N6ng dQ hai hormon nay d nguoi Viet Nam duoc ghi trong bang duoi day (Nguyen Can, Vi1 Th1.1C Nga va CS, 1995.)

Bang 7·1. N6'ng dt) LH va FSH a phlf nit Vi¢t Nam.

LH (lUll) FSH (lUll)
GD I cua CKKN 3,94- 7,66 1,45- 2,33
Nong dQ dinh 44,12- 59,60 8,87- 11,43
Ngay xuat hien dinh 16,54 ± 3,86 16,06 ± 2,89
GD II cua CKKN 2,44- 4,09 043- ° 84
Nam gidi 4,90 ± 2,12 4,60 ± 1,91 2.4.4. Di~u hoa hai tiet

- Do tac dung dieu hoa nguoc cua hormon sinh due.

Tac dung dieu hca nguoc am tinh cua testosteron,

700
\J\ 80
2000 ~ 60
'"'
<,
40 E:;
'-'
~
0 '--'
1000 :t:.
'J WO-----L----,~2-0----~--2-4~O----~---J-6~O----~--~4~OO Ph:'

1. Nhfrng thay d6i ve hoat dOng dien ghi duoc tai vung giua nen - vung duci deli.

2. Nhip LH (j mau ngoai bien cua khi Rhesus dii bi ciit budng trung duoc gay me bang barbital,

Hinh 7·13. Xung di~n gay biii tilt GnRH vii nhip LH

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1'IJ6ng dQ testosteron tang trong mau c6 tac dung uc che cac tuyen chi huy va lam giarn bai tiet ca FSH va LH. Nguoc 19-i neu nang dQ testosteron giarn lai c6 tac dung kich thich bai tiet FSH va LH.

Tac dung dieu hoa ngucc am tinh cua testosteron chu yeu la tac dung len su bai tiet GnRH cua vung duoi dai va thong qua hormon giai ph6ng nay d~ dieu hoa bai tiet hai hormon FSH va LH can tac dung true tiep len tuyen yen thi rat yeu.

• Tac dung dieu hca ngucc am tinh cua estrogen va progesteron.

Ca estrogen va progesteron deu c6 tac dung uc che' bai tiet FSH va LH tuy nhien khi c6 mat progesteron thi tac dung uc che cua estrogen duoc nhan len nhieu Ian.

Khac vdi testosteron, hai hormon sinh due nir lai c6 tac dung dieu hoa ngucc len su bai tiet FSH va LH bang each tac dung true tiep len tuyen yen can tac dung len vung dudi d6i thi yeu hen va chu yeu la d~ lam thay d6i tan so nhip bai tiet GnRH.

• Tac dung dieu hoa nguoc ducng tinh cua estrogen.

Vao thoi di~m 24-48 gid truce khi ph6ng noan nong d9 estrogen trong mau rat cao da kich thich tuyen yen bai tiet FSH va dac biet la LH voi nong dQ rat cao. Ki~u dieu hoa nay duoc goi la dieu hoa nguoc duong tinh.

• Tac dung uc che cua inhibin.

Inhibin do te bao Sertoli va te bao hat cua hcang th~ bai tiet c6 tac dung uc che bai tiet FSH d ca nam va nU' gioi, Tac dung nay th~ hien khi tinh trung duoc san sinh nhieu nharn dieu hca qua trinh san sinh tinh trung va VaG cuoi chu ki kinh nguyet hang thang d~ lam giarn FSH va LH d thoi di~m nay.

2.5. HORMON KICH THICH RAI TIET suA· PROLACTIN (PRL)

t

2.5.1. Ban chat hoa hoc

Prolactin l a mot hormon protein c6 198 acid amin vdi t rorig luon g p h a n tv 22.500.

2.5.2. Tilc d urrg

Prolactin c6 tac dung kich thich bai tiet siia tren tuyen vu da chiu tac dung cua estrogen va progesteron.

Prolactin binh thuong duoc bai tiet vdi nang dQ rat thap nhung khi nguoi phu nfr c6 thai, nong dQ prolactin duoc bai tiet tang dan tU tuan thu 5 cua thai nhi cho tdi hie sinh. Nang dQ prolactin trong thoi ki nay tang gap 10-20 Ian so voi binh thuong. Tuy nhien do estrogen va progesteron c6 tac dung uc che' bai tiet sira nen trong khi c6 thai mac du ndng dQ prolactin rat cao nhung luong sira duoc bai tiet chi khoang vai mililit m6i ngay. Ngay sau khi dua tre duoc sinh ra, ca hai hormon estrogen va progesteron giam dQt ngdt t9-0 dieu kien cho prolactin ph at huy tic dung bai tiet sira.

64

2.5.3. Dieu hoa bai W~'t

o nguoi Viet Narn binh thucng, nong dQ prolactin d nam gidi vao khoang 110- 510 va nir gidi la 80-600 mUll (Nguyen CQ_n, Vii Thuc Nga va CS, 1995). Khi co thai nong dQ tang cao, sau khi sinh vai tuan noug dQ prolactin trd lai mire cd sd neu khong cho con bu, neu cho con bu nong dQ prolactin van cao. Su bai tiet prolactin ducc dieu hoa dudi anh hucng cua hormon vung dudi d6i va mot so yeu to khac,

• Vai tro cua hormon vung dudi d6i: Khac vdi cac hormon khac cua tuyen yen chu yeu chiu tac dung kich thich cua hormon vung dudi d6i, prolactin lai chiu tac dung ung che manh cua PIH dude bai tiet tu vung dudi d6i. Khi t6'n thucng vung dudi d6i hoac t6'n thucng h~ mach cira dudi doi-yen su bai tiet prolactin tang len trong khi cac hormon khac cua tuyen yen lai giarn di .

• Dopamin ducc bai tiet tU nhan cung (arcuate nuclei) cua vung dudi d6i co tac dung UC che bai tiet prolactin d~ duy tri mot nong dQ thap trong tinh trang binh thucng. Khi dang cho con bu Dopamin lai kich thfch bai tiet prolactin.

• TRH ngoai tac dung giai phong hormon TSH no can la hormon co tac dung manh trong viec kich thich tuyen yen bai tiet prolactin.

• Prolactin dude bai tiet khi co cac kich thich true tiep vao num vu (dong tac mut mut vii cua tre).

3. cAe HORMON THUV SAU TUVEN Yf~N

Hai hormon ducc bai tiet tU thuy sau tuyen yen co ngucn goc tU vung dudi d6i.

Chung duoc bai tiet tu cac ncron rna than khu tru d nhan canh nao that va nhan tren thi. Sau khi ducc t6'ng hcp chung duoc van chuyen theo sci true den chua d cac tui narn trong tan cung than kinh khu tru d thuy sau tuyen yen. Hai hormon do la hormon oxytocin va ADH.

3.1. HORMON ADH

3.1.1. Ball chat h6a hQC

ADH hay can co ten la vasopressin la mot peptid co 9 acid amin vdi diu true nhu sau:

Cys- Tyr- Phe- Gln- Asn- Cys- Pro- Arg- Gly- NH2•

ADH duoc bai tiet chu yeu tU cac noron thuoc nhan tren thi, nhimg noron nay cung co kha nang bai tiet oxytocin nhung vdi luong chi bang 116 hrcng hormon chinh.

3.1.2. Tac du ng

• Vdi mot lucng rat nho chi 2 ng ADH khi tiern cho nguoi se lam giarn bai tiet nude ti~u ella ngudi nay do ADH co tac dung lam tang tai hap thu nude dong lUQIl xa va oug gop.

65

Neu khong co ADH, ang gop va ang hron xa hau nhu khong tai hap thu nude lam cho mot lucng IOn nude mat di qua duong nude ti@u. Nguoc lai vdi su co mat cua ADH tinh tharn vdi nude cua ong luon xa va ong gop tang len nhieu Ian cho phep nude duoc tai hap thu trd lai co th@ lam cho nude ti@u duoc co dac.

Co che tac dung cua ADH tai ang luon xa va ang gop moi chi duoc hi@u biet mot phan. Khong co ADH, mang ang than hau nhu khong cho nude tham qua. Tuy nhien phia trong cua mang co nhimg tui dac biet, nhimg tui nay co cac 16 co kha nang tharn nude manh. Khi ADH tac d9ng tren te bao, budc d:1u tien la gAn voi receptor d mang te bao ang hron xa va ang gop, r6i tao thanh AMP vong. Duoi tac dung cua AMP vong cac thanh phan narn trong nhirng tui dac biet do duoc phosphoryl hoa va lam cho cac tui nay long VaG mang te bao. Khi nhfrng tui nay 16ng ghep VaG mang te bao thi chinh chiing se lam cho mang te bao co nhimg vung tham duoc nuoc. Tat ca nhirng hien tuong nay xay ra trong khoang tu 5-10 phut, Neu khong co ADH thi qua trinh tren se xay ra theo chien nguoc lai.

Nhu v~y nho co ADH rna nude khuech tan tv do tu long ang than VaG dich quanh ang r6i VaG mau nho su chenh lech vg ap suat tharn thau,

• Vdi nong d9 cao, ADH co tac dung lam co manh cac ti@u d9ng mach d toan co th@

do do lam tang huyet ap. Chinh vi If do nay rna ADH can co ten thu hai la vasopressin.

3.1.3. Di~u hoa bai tiet

~ Di~u hoa bang ap suat th~m thau

Khi tiern dich uu truong VaG dong mach cung cap mau cho vung duoi d6i, cac noron bai tiet ADH d nhan tren thi va nhan canh nao that lap tire chuyen tin hieu xuong thuy sau tuyen yen va gay giai phong ADH VaG mau tuan hcan, doi khi hrong ADH duoc bai tiet tang tdi 20 l:1n so vdi binh thuong. Nguoc lai khi tiern dich nhuoc truong VaG dong' mach tren thi se lam dung tin hieu gay bai tiet ADH.

Thoi gian ban huy cua ADH khoang 15-20 phut. Ncng d9 ADH co th~ thay d6i tu rmrc rat thap den mire rat cao chi trong khoang thoi gian vai phut.

Co che chinh xac d@ giai thich vai tro dieu hoa bai tiet ADH cua ap suat tharn thau van chua ro.

Nguoi ta cho rang' d mot so vung d tren hoac g:1n vung dirdi d6i co cac receptor nhan cam ve su thay d6i ap suat tharn thau. Khi dich ngoai bao qua darn dac, do co su chenh lech vg ap suat tham thau nen dich bi keo ra khoi cac receptor ap suat tham thau lam cho kich thuoc cua nhimg receptor nay bi giam. Chinh su thay d6i kich thiroc cua nhfrng receptor nay da phat cac tin hieu than kinh den vung duoi d6i d@ gay bai tiet ADH. Nguoc lai khi dich ngoai bao bi pha loang thi nude lai duoc khuech tan tu dich ngoai bao VaG trong te bao receptor va lam giam tin hieu bai tiet ADH.

M9t so nha nghien cuu cho rang' nhirng receptor nay narn d ngay vung duoi d6i (co th@ narn ngay d nhan tren thi), mot so khac lai cho rang no narn d vung mach (organum vasculosum) thuoc thanh bung truce cua nao that ba.

66

Nhu v:%ly co che dieu hoa bai tiet ADH do ap suat tham thau c6 th@ duoc t6m tiit nhu sau:

Khi dich th@ darn dac (ap suat tharn thau tang), nhan tren thi bi kich thich, cac tin hieu kich thich se truyen den thuy sau tuyen yen va gay bai tiet ADH. ADH duoc mau dua den te bao ong than lam tang tinh tharn doi voi nude cua te bao ong than dac biet ong g6p do vay h:lu hst nude duoc tai hap thu trong khi do cac chat dien giai van duoc tiep tuc dua ra nude ti@u do do nude ti@u duoc co dac,

• Di~ll hoa bang th~ tich mall

- Th@ tich mau giarn la mot tac nhan kich thich manh gay bai tiet ADH (vasopressin). Tac dung nay dac biet manh khi th@ tich mau giarn tU 15-25%, khi do nong d9 ADH c6 th@ tang tdi 50 Ian cao hon binh thuong.

- 0 tam nhi d~c biet tam nhl phai c6 nhieu receptor ve sue cang. Khi mau d6 ve tam nhi phai nhieu, cac receptor nay bi hung phan, tin hieu truyen ve nao lam uc che bai tiet ADH. Nguoc lai neu mau ve nhi it, cac receptor nay khong hung phan thi lai c6 tac dung kich thfch bai tiet ADH.

Ngoai tam nhi cac receptor ve sue cang can c6 mat ca d dong' mach canh, dong mach chu va cac vung cua ph6i. Nhiing receptor nay cling tharn gia dieu hoa bai tiet ADH.

3.2. OXYTOCIN

3.2.1. Ban cha't hoa hoc

Oxytocin cling la mot peptid c6 9 acid amin, chi c6 acid amin thu 8 khac vdi

phan tli ADH (thay arginin bang leucin)

Cys- Tyr- Phe - Gln- Asn- Cys- Pro- Leu- Gly- NHz. 3.2.2. Tac du ng

• Tac dung tren tli cung.

Oxytocin c6 tac dung co tli cung manh khi dang mang thai dac biet cang g:ln cudi thoi ky c6 thai tac dung co tli cung cua oxytocin cang manh. Vi tac dung nay rna nhieu nguoi cho rang oxytocin c6 lien quan den co che' de. Tren mot so loai dong vat neu khong c6 oxytocin dong vat nay khong de dUQC. 0 nguoi nong d:Q oxytocin tang trong khi de dac biet tang trong giai doan cuoi,

o nhung nguoi de kh6 do con co tli cung yeu nguoi ta thuong tiern truyen oxytocin d@ lam tang con co tli cung (de chi huy).

• Tac dung bai xuat sira.

Oxytocin c6 tac dung co cac te bao bi@u rna co (myoepithelial cells) la nhimg te bao nam thanh hang rao bao quanh nang tuyen sira.

Nhirng te bao nay co lai se ep vao nang tuyen voi ap IVc 10-20 mmHg, va d~y siia ra ong tuyen, khi dua tre bii thi se nhan duoc sua,

Tac dung nay cua oxytocin duoc goi la tac dung bai xuat sua, khac vdi tac dung gay bai tiet sira cua PRL.

67

3.2.3. Di~u hoa hili tiet

Binh thuong nong' dQ oxytocin huyet tuong 18. 1- 4 pmol/l. Oxytocin duoc bai tiet do kich thich co h9C va tam H.

• Kich thfch true tiep VaG num vu: chinh dong tac mut num vii cua dua tre la nhirng tin hieu kich thich duoc truyen ve t.uy song r6i vung dudi d6i lam kich thich cac noron a nhan canh nao that va nhan tren thi. Nhirng tin hieu nay duoc truyen xuong thuy sau tuyen yen d~ gay bai tiet oxytocin.

• Kich thfch tam H hoac kich thich he giao cam.

Vung duoi d6i luon nhan duoc cac tin hieu tu h~ limbic do v~y tat ca nhimg kich thich tam H hoac he giao cam c6 lien quan den hoat dong' cam xiic deu c6 anh huang den vung duoi d6i lam tang bai tiet oxytocin va do v~y tang bai xuat sua. Tuy nhien neu nhirng kich thich nay qua manh hoac keo dai thi c6 th~ uc che bai tiet oxytyocin va lam mat sua a cac ba me dang nuoi con.

4.1. SUY GIA.M TUYEN YEN TOAN nO

'I'huat ngfr suy giarn tuyen yentoan bQ duoc dung d~ chi tinh trang giarn bai tiet tat ca cac hormon tuyen yen. Tinh trang nay c6 th~ c6 nguon goc b:lm sinh cling c6 th~ do mac phai sau nay.

4.1.1. Berih lim tuyen yen

Hau het cac truong hop lun deu do thieu hormon tuyen yen trong thoi ki nien thieu, Nhin chung co th~ phat tri~n can doi nhung rmrc dQ phat tri~n thi giarn r6 ret, dua tre 10 tu6i chi' bang dua tre 4-5 tu6i, nguoi 20 tu6i chi b:1ng,dua tre 7-10 tu6i.

Nguoi lun tuyen yen khong c6 day thi va hormon huang sinh due khong bao gio duoc bai tiet du do v~y chirc nang sinh due khong th~ phat tri~n nhu nguoi trudng thanh binh thuong.

C6 khoang mot phan ba nhirng nguoi lun loai nay chi' giarn bai tiet GH do v~y clnrc nang sinh due van phat tri~n va van co kha nang sinh san.

o nhirng ngudi lun pygmy (Chau Phi), luong GH duoc bai tiet binh thuong hoac

cao nhung h91:;1i khong c6 kha nang t:;10 ra somatomedin C la chat dap ung vdi GH.

4.1.2. B~nh suy tuyen yen d nguoi IOn

- Suy tuyen yen to an bQ a nguoi IOn thuong do mot trong ba nguyen nhan sau:

• U S9 hau (craniopharyngioma)

• Ute bao khong bat mau ~ tuyen yen (chromophobe tumor).

• T:1c mach mau tuyen yen, dac biet hay xuat hien a cac ba me sau sinh con. - Cac bi~u hien cua suy tuyen yen nguoi IOn la bi~u hien cua :

• Suy tuyen giap.

• Giarn bai tiet hormon chuyen h6a ducng cua vo thucng than.

• Giarn bai tiet cac hormon hudng sinh due dan tdi giarn hoac mat chuc nang sinh due.

Hinh anh chung cua benh la mot tinh trang 1d do, cham chap do thieu hormon tuyen giap; tang can do thieu tac dung thoai h6a me cua hormon G H, ACTH, vo thuong than va hormon tuyen giap; mat tat ca chuc nang sinh due.

Ngoai trir chuc nang sinh due, cac rei loan khac c6 th~ diroc dieu tri khoi nho hormon tuyen giap va vo thuong than.

4.2. Bf~NH KH6NG LO

Nguyen nhan gay benh la do cac te bao bai tiet GH tang cuong hoat dong' hoac do u cua te bao ua acid. Ket qua la hormon GH duoc bai tiet qua mire. Tuy nhien benh khong' 10 chi xuat hien khi tinh trang nay xay ra VaG hie con tre (truce tu6i trucng thanh),

Bi~u hien cua benh la tinh trang phat tri~n nhanh va qua muc cua tat ca cac mo trong co th~ bao gam ca xuong va cac phu tang lam cho nguoi do to cao qua muc binh thuong nen duoc goi la nguoi khong' 10.

Nhirng nguoi khcng 10 thucng bi tang duong huyet va khoang 10% c6 th~ bi benh dai thao duong

Hfru het cac benh nhan khong 16 thuong chet khi con tre trong tinh trang suy tuyen yen toan bQ vi ph an 16n nguyen nhan gay khong' 10 la do u te bao bai tiet G H, khoi u nay cang phat tri~n thi cang chen ep VaG cac te bao bai tiet cac hormon khac cua tuyen yen. Tuy nhien neu duoc chi'in doan kip thoi, benh c6 th~ duoc ngan chan bling vi phau thuat b6c tach khoi u hoac tia xa.

4.3. n1):NH TO VAU NGON

Neu u te bao ua acid xay ra VaG sau tu6i truong thanh nghia Is xay ra sau khi cac sun d dau xuong dai dil duoc cot h6a thi benh nhan S8 khong c6 bieu hien khong 10 nhung cac mo mern van phat tri~n va cac xuong d:ftc biet xuong det va xuong nho c6 th~ day len.

Benh nhan bi benh nay S8 c6 hinh anh dau to, ham nho ra, tran nho ra, miii to, moi day, ludi to va day, ban tay to, ban chan to, phu tang to, doi khi c6 ca su bien dang cQt song lam lung guo

4.4. Bf~NH vAl THAo NHAT

T6n thuong vung dudi doi hoac thuy sau tuyen yen S8 lam giam luong bai tiet ADH. Trieu chung chinh cua benh la dai nhieu nhung nang dQ cac chat dien giai trong nude ti~u lai rat thap nen benh duoc goi la benh dai thao nhat.

69

TUYEN GIAp

1. D~C DIEM CAU T~O

Tuyen giap narn ngay duci thanh quan va d phia truce khi quan, g6m hai thuy trai va phai, a nguoi trucng thanh tuyen giap nang 20-25g.

Tuyen giap g6m nhirng den vi cau tao duoc goi la nang giap, c6 ducng kinh khoang 100-300 micromet. Nhimg nang nay chua dcly cac chat bai tie't dude goi la cac chat keo trong long nang va duoc 16t bang mot ldp te' bao hinh khoi la nhirng te' bao bai tiet hormon VaG long nang, day te' bao tiep xuc vdi mao mach, dinh te' bao tiep xuc vdi long nang (Hinh 7-14).

Tuyen giap la noi rat giau h~ thong mao mach, trong m6i phut hrcng mau de'n' tuyen giap ldn gap 5 lcln trong hrcng tuyen, day la noi duoc cung cap mau nhieu nhat co th~ (ngoai tru tuyen vo thucng than).

Cac te' bao 16t nang giap bai tiet hai hormon la triiodothyronin (T3) va tetraiodothyronin (T 4). Nhf:lng hormon nay c6 nhieu chirc nang quan trong dac biet chuc nang chuyen h6a.

Ngoai ra canh cac nang giap, cac te' bao canh nang bai tie't ra hormon calcitonin la hormon tham gia trong chuyen h6a calci.

1- Te' bao bieu rna 16t nang giap 2- Long nang chua chat keo

3- Mao mach chua hdng cau

Hinh 7-14. Cdu t(,LO tuyeri gidp

70

Cac hormon tuyen giap duoc t6ng hop tai te bao cua nang giap. Qua trinh t6ng hop hormon trai qua 4 giai doan (Hinh 7-15)

2.1. BAT IOD

Iod cua thuc an duoc hap thu vao mau va duoc mau dua den te bao tuyen giap bang co che' van chuyen tich cue do la co che born iod. Mang day te bao nang giap c6 kha nang dac biet do la kha nang born iod vao trong te bao nang giap.

Qua trinh born iod til mau vao te bao nang giap va giu iod lai do duoc goi la qua trinh bat iod.

Nho co che. bom tich cue nay rna d tuyen giap binh thuong ncng di? iod trong tuyen giap c6 th~ cao gap 30 15.n nong di? trong mau, Khi tuyen giap hoat dong tai da rmrc chenh lech c6 th~ len tdi 250 15.n.

Dung iod ph6ng X? (I131) d~ kiem tra mire di? b:it iod ta c6 th~ biet duoc tinh trang hoat dong' cua te bao tuyen giap, 0 nhimg nguoi uu nang tuyen giap hoac buou c6 do thieu cung cap iod, di? tap trung iod phong X? trong tuyen giap thuong cao.

Mi?t so' ion h6a tri mot nhu perclorat, thiocyanat c6 kha nang uc che canh tranh sir van chuyen iod vao te bao tuyen giap do chung sit dung canh tranh cung loai bom vdi born iod.

2.2. OXY HOA ION IODUA THANH DA.NG OXY HOA eVA IOD NGUYEN Ttl

Tai dinh cua te bao nang giap, ion iodua duoc chuyen thanh dang oxy h6a cua nguyen tit iod do la iod mdi sinh (lo)ho?c l3-. Nhirng dang nay c6 kha nang g:in true tiep voi mot acid amin la tyrosin.

Phan ung oxy h6a ion iodua duoc thuc d:lY nho men peroxidase va chat phoi hop voi men nay la hydrogen peroxidase. Men peroxidase thuong khu tru d mang dinh te bao, noi tiep xuc vdi long nang do v?y hien tuong oxy h6a iod xay ra d nhimg vi tri nhat dinh tren te bao noi c6 thyroglobulin do th~ Golgi san xuat d~ no c6 thJ giin ngay vdi hormon tuyen giap sau khi duoc t6ng hop d~ r6i di vao du trit d long nang.

Khi h~ thong men peroxidase bi uc che hoac thieu men peroxidase b:lm sinh thi muc bai tiet hormon T 3- T 4 c6 th~ giarn bang khong.

Cac thuoc khang giap thong thuong loai thioure nhu methythiouracil uc che men peroxidase nen uc che t6ng hop hormon T 3- T 4.

2.3. GAN IOD NGUYEN Ttl 6 DA.NG OXY HOA V Ao TYROSIN DE TA.O THANH HORMON DVOI DA.NG GAN VOl THYROGLOBULIN

Trong te bao nang giap, iod d dang oxy h6a lien ket vdi men iodinase nen qua

71

triuh gi'in voi tyrosin xay ra rat nhauh chi troug vai giay den vai phut d~ tao thanh 2 dang tien chat la monoiodotyrosin (MIT) va diiodotyrosin (DIT)

HO- 0 - CH2 - CHNH2 - COOH + 12 -7 Tyrosin

I

HO 0. - CH2 - CHNH2 - COOH va I

Diiodo tyrosin (DIT)

I

HO -0 - CH2 - CHNH2 - COOH Monoiodotyrosin (MIT)

Hai tien chat hormon la MIT va DIT se trung hop vdi nhau d~ tao thanh hai hormon tuyen giap la triiodo thyronin (T 3) va tetraiodothyronin (T4).

I I

MIT + DIT ~ HO -0 - 0- O-CH, - CHNH, - COOH I

3,5,3' Triiodothyronin.

I I

DIT + DIT -7 HO-O - 0 - 0- CH2 - CHNH2 - COOH

I I

Tetraiodothyronin (Thyroxin)

Ngay sau khi duoc tao thanh, ca MIT. DIT, T3, va T4 deu gi'in vdi thyroglobulin va duoc van chuyen qua mang dinh te bao nang giap d~ du trfi trong long nang. M6i phan ti'i thyroglobulin thuoug gi'in til' 1-3 ph an tli thyroxin. Luong hormon du trit trong tuyen giap du d~ cung cap trong 2-3 thang. Vi vQ.y khi ngirng tr$ qua trinh sinh t6ng hop hormon T 3- T 4, anh huong ella thieu hormon thuong chi quan sat diroc sau vai thang.

2.4. GIAI PHONG HORMON TUYEN GIAp V Ao MAu

Budc dau tien cua giai doan giai phong hormon VaG mau la te bao nang giap hap thu cac giot keo til long nang giap bang' each mang cua phan dinh te bao tho ra

72

nhirng tua nhu chan gia d~ bao quanh cac giot keo va hinh thanh cac tui frm bao. Bang each nay cac giot keo da di qua mang dinh d~ VaG trong te bao nang giap,

Ngay sau do cac men tieu h6a ducc tiet tu cac b9C lysosom tham VaG cac tui frm bao tron Ian vdi chat keo d~ t:;10 thanh cac tiii tieu h6a. Dudi tac dung cua cac men phan giai protein, cac phan ttt thyrogobulin S8 duoc tieu h6a va giai ph6ng T:)- T, d dang tv do. Hai hormon S8 khuech tan qua mang day cua te bao nang giap d~ VaG cac mao mach narn quanh nang giap.

Cac phan ttt MIT va DIT sau khi duoc t:;10 thanh chung cung g:111 vdi thyroglobulin nhung chi 114 IUQng cua chung trd thanh hormon tuyen giap. So con lai ciing ducc du trfr trong long nang. Trong qua trinh tieu hoa phan thyroglobulin d~ giai phong T3-T4 VaG mau, 2 phan ttt tien chat nay ciing ducc giai phong khoi thyroglobulin trd thanh MIT va DIT tv do nhung chung khong duoc bai tiet VaG mau, Dudi tac dung cua men deiodinase, iod duoc tach khoi MIT va DIT va iod ducc te bao tuyen giap stt dung lai d~ t6ng hop hormon tuyen giap tiep tuc, Neu thieu men iodinase barn sinh S8 gay tinh trang thieu iod vi mat qua trinh tai stt dung iod.

~Thyrog/o/;IIJ;/l 7j

o

C> 0 o>»: Thl/ron/oW/ln 74-

000 t '::J

o~ I

I---t+

1- Mau

2- Te bao nang giap 3- Long nang

Hinh 7-15. Sinh t6ng hop va gidi ph6ng T3 - T4.

3. NHU CAU IOD v A PHAN BO IOD TRONG TUYEN GIAP

Iod cua tuyen giap duoc cung cap tu thuc an. Nhu cau iod khoang 1 mg cho mot tuan. d tre em va phu nlt c6 thai nhu cau iod cao hen binh thuong. D~ ngan ngua

73

tinh trang thieu iod, trong muoi an c6 th~ cho them mot luong iod voi ty l~ NIINaCl la 11100.000.

Iod cua thuc an duoc hap thu qua duong tieu h6a vao mau theo phuong thuc giong' ion cr. Binh thuong hau nhu chiing duoc bai xuat rat nhanh qua duong nude ti~u. Chi khoang 1/5 lucng iod thuc an duoc dua tu mau VaG te bao nang giap d~ t6ng hop hormon tuyen giap.

LUQng hormon duoc du trfi trong tuyen giap c6 du kha nang duy tri tinh trang binh thuong tU 2-3 thang.

T6ng luong iod duoc chua trong tuyen giap khoang 10 mg bao g6m:

- 95% luong iod narn ngoai te bao nang giap va duoc du tru duoi dang chat keo trong long nang giap, trong do:

+ 2/3 d dang iodotyrosin chua heat dong' (MIT & DIT).

+ 113 d dang iodothyronin c6 kha nang hoat d9ng (T3-T4)' Ty l~ giira T31 T 4 la 1/9- 1/10.

Ty l~ giira iodotyrosin 1 iodothyronin la 2/1.

- 5% luong iod con lai narn trong te bao nang giap.

4. V,).N CHUYEN V A llAI XUAT HORMON TUYEN GIAP

Hormon tuyen giap duoc giai ph6ng VaG mau 93% la T4 chi c6 7% la T3. Tuy nhien chi sau vai ngay hau het T4 se dan dan bi mat mot nguyen tv iod d~ tao thanh dang T3. Nhu vay T3 chfnh la dang heat dong' tai te bao. M6i ngay khoang 35 Ilg T3 duoc sV dung d cac mo.

Trong mau chi mot hrcng rat nho hormon narn dudi dang tv do (0,05% T4 va 0,5% T3) phan IOn giin voi protein huyet tuong (99,95% T4 va 99,5% T3) trong do chu yeu giin voi globulin (TBG) va rnot phan nho giin voi prealbumin (TBPA).

Thyroxin sau khi duoc tiern vao co th~ phai sau 2-3 ngay moi bat ctilu co tac dung va tac dung dat mire toi da sau 10-12 ngay. Thoi gian ban huy cua thyroxin khoang 15 ngay nhung tac dung cua n6 con t6n tai trong mot thoi gian tir 6 tuan den 2 thang.

Sd di thyroxin c6 thci gian tiern tang va thoi gian tac dung keo dai nhu v~y c6 Ie vi d trong huyet tuong cling nhu trong te bEW rna n6 ~eu giin vdi protein do do giai ph6ng VaG te bao cham, hon niia each tac dung tai te bao cua thyroxin cung lam cho thoi gian tac dung keo dai khac voi nhieu hormon khac.

Sau khi tac dung T3-T4 duoc chuyen h6a bang each tach iod, tach acid amin r6i ket hop vdi acid glucuronic va duoc bai xuat qua duong mat VaG ruot r6i thai ra ngoai theo phan, chi mot luong nho dUQC thai qua duong nude ti~u.

74

Bang 7-2. N6ng dij T3-T4 eua ngztiJi Vi¢t Nam.

Tu6i T4 (nMolll) T3 (nMolll)
So sinh (mau cuong ron) 130,87 ± 22,54 0,79 ± 0,28
n = 30
1- 5 tu6i 122,80 ± 23,65 2,49 ± 0,36
n = 22
6- 10 tu6i 119,14 ± 26,23 2,34 ± 0,52
n = 30
11-15 tu6i 112,14 ± 23,53 2,10 ± 0,42
n = 30
16- 60 tu6i 107,03 ± 21,80 2,02 ± 0,42
n = 36 n = 143
61- 88 tu6i 101,03 ± 21,80 1,50 ± 0,37
n = 34 5.1. TAc Dl,lNG Lf~N su PHAT TRIEN co THE

Tac dung cua hormon tuyen giap tren su phat trien co th~ da duoc biet tu lau thong qua mot thuc nghiern kinh di~n do la nuoi nong noc trong nude c6 thyroxin thi nong noc mat duoi d~ trd thanh ech nhanh hen binh thuong.

a nguoi, tac dung cua hormon tuyen giap len su phat tri~n co th~ chu yeu th~ hien trong thoi ky dang IOn cua dua tre.

- Lam tang toc d9 ph at trien,

,

• a nhirng dua tre bi uu nang tuyen giap, S1;i ph at trien cua xuong nhanh hon nen dua tre cao sam hen so vci tu6i nhung dong thoi xucng cling truong thanh nhanh hen, cot h6a sam hon lam cho thoi ky trucng thanh cua dua tre ngan 19.i va dua tre c6 chieu cao cua nguci trucng thanh sam hon,

• a nhiing dua tre bi nhucc nang tuyen giap, rnuc phat trien se cham 19.i, neu khong duoc phat hien va dieu tri sam dua tre se bi lun.

- Thuc dfry S1;i trucng thanh va phat tri~n nao trong thoi ky bao thai va trong vai nam dau sau khi sinh. Neu lucng hormon tuyen giap khong ducc bai tiet du trong thoi ky bao thai thi su ph at tri~n va trucng thanh cua nao se cham 19.i, nao cua dua tre se nho hen binh thucng. Neu khong duoc dieu trj bang hormon tuyen giap ngay vai ngay den vai tuan sau khi sinh thi tri tue cua dua tre se khong phat tri~n.

5.2. TAc Dl,lNG Lf~N CHUYEN H6A TE BAO

• Hormon tuyen giap lam tang hoat dong chuyen h6a cua hau het cac rna trong co th~. Mire chuyen h6a co Sd c6 th~ tang tu 60-100% tren muc binh thucng neu hormon tuyen giap duoc bai tiet nhieu,

75

• Tang toe dQ cac phan ung h6a h9C, tang tieu thu va thoai hoa thuc an d~ cung cap nang 1 uong.

• Tang so lucng va kich thudc cac ty th~ do do lam tang t6ng hop ATP d~ cung cap nang lucng cho cac hoat dong chuc nang cua cd th~. Tuy nhien s11 tang so luong va heat dong cua ty th~ co th~ vua la nguyen nhan lam tang hoat dong' cua cac te bao vua la ket qua cua s11 tang hoat dong' cua te bao.

Khi nang dQ hormon tuyen giap qua cao. cac ty th~ phong to se gay ra tinh trang mat can xung gifra qua trinh oxy h6a va phosphoryl h6a nen mot luong Ion nang lucng se thai ra duoi dang nhiet chu khong duoc t6ng hop duoi dang ATP.

Tren thuc te c6 mot cau hoi rat kh6 giai dap la d nguoi bi ngQ dQc giap thi lucng hormon tuyen giap bao nhieu thi du cao d~ gay nen tinh trang tren?

- Tang van chuyen ion qua mang te bao.

Hormon tuyen giap c6 tac dung hoat h6a men ATPase cua born natri-kali do do lam tang van chuyen ca ion Na" va K+ qua mang te bao cua mot so mo. Vi qua trinh nay can s11 dung nang luong va tang sinh nhiet nen nguoi ta cho rang day chinh la mot trong nhung co che' lam tang rmrc chuyen h6a co th~ cua hormon giap.

5.3. TAc Dl)NG Lf~N CHUYEN H()A GLUCID

Hormon tuyen giap tac dung len hau nhu tat ca cac giai dean cua qua trinh

chuyen h6a glucid bao gam:

• Tang nhanh thoai h6a glucose d cac te bao,

• Tang phan giai glycogen.

• Tang tao ducng mdi.

• Tang hap thu glucose d ruot.

• Tang bai tiet insulin.

Do nhirng tac dung tren nen hormon tuyen giap lam tang nang dQ glucose trong rna u nh ung chi tang nhe.

5.4. TAc Dl)NG Lf~N CHUYEN HOA LIPID

Tat ca cac giai doan cua chuyen h6a lipid cling tang dudi tac dung cua hormon tuyen giap vi lipid chinh 1<1 nguon chu yeu cung cap nang lucng cho co th~.

• Tang thoai h6a lipid d cac rna rna du trl1 do d6 lam tang n6ng di? acid beo W do trong rna u.

• Tang oxy h6a acid beo t11 do d mo.

• Giarn lucng cholesterol, phospholipid, triglycerid d huyet tuong do v~y nguoi bi nhuoc nang tuyen giap keo dai c6 th~ c6 tinh trang xo vita mach.

76

MQt trong nhfrng co che lam giarn nong dQ cholesterol trong mau cua hormon tuyen giap do la do chung lam tang toc dQ bai xuat cholesterol qua mat roi thai ra ngoai theo phan.

MQt co che khac mra do la hormon tuyen giap lam tang so lucng cac receptor giin dac hieu voi lipoprotein ty trong thap tren te bao gan do do lam tang qua trinh lay cholesterol ra khoi mau.

5.5. TAc DUNG TREN CHUYEN HOA PROTEIN

Hormon tuyen giap vua lam tang t6ng hop protein vua lam tang thoai hoa protein. Trong thoi ky dang phat trien, tac dung tang t6ng hop protein manh hon nen co tac dung thuc dfry lam tang toc dQ phat tri~n. NguQC lai khi hormon tuyen giap duoc bai tiet qua nhieu, cac kho protein du trf:l bi huy dong va giai phong acid amin VaG mau,

5.6. TAc DUNG Lf~N CHUYEN HOA VITAMIN

Do hormon tuyen giap lam tang nong dQ va heat dong cua nhieu men, rna vitamin lai la thanh phan co ban d~ cau tao enzym hoac coenzym nen khi nong dQ hormon giap tang se lam tang nhu cau tieu thu vitamin. Neu cung cap kh6ng du se gay tinh trang thieu vitamin.

5.7. TAc Dl.)NG LEN HI): THONG TIM M1\CH

• 'I'ac dung len mach rnau.

Hormon giap lam tang chuyen hca cua hau het te bao do do lam tang mire tieu thu oxy d6ng thoi tang giai phong cac san pham chuyen hoa cuoi cung; Chinh nhirng chat nay co tac dung gian mach d hau het cac rna trong co th~ do v~y lam tang IUQng mau dac biet IUQng mau den da bdi vi co th~ co nhu cau tang thai nhiet.

Khi IUQng rnau den rna tang thi luu IUQng tim cling tang dai khi co th~ tang 60% tren mire binh thuong neu hormon tuyen giap duoc bai tiet qua nhieu,

• Tac dung len nhip tim.

Hormon tuyen giap co tac dung tang nhip tim ra hen la tang luu IUQng tim. Tac dung nay co le do hormon tuyen giap kich thich true tiep len tim do vay khong chi lam tim dap nhanh rna con lam tim dap manh hen,

Su dap irng nhay cam cua nhip tim doi voi hormon tuyen giap la mot dau hieu quan trong rna cac nha lam sang hay dung d~ danh gia mire dQ bai tiet hormon tuyen giap.

• Tac dung len huyet ap.

Duoi tac dung cua hormon tuyen giap thi huyet ap trung binh khong thay d6i.

Tuy nhien do tim dap nhanh va manh hon nen huyet ap tam thu co th~ tang tu 10-15 mmHg, nguoc lai huyet ap tam truong lai giam do gian mach d nhirng nguoi bi uu nang tuyen giap,

T6 - SLH

77

5.S. TAc Dl)NG LEN HI): TH6NG THAN KINH co

• Tac dung len h~ than kinh trung uong.

Nhin chung hormon tuyen giap co tac dung thuc d~y su phat tri~n ca vg kich thudc ca vg chuc nang cua nao,

Nhuoc nang tuyen giap gay tinh trang cham chap trong suy nghi. Neu nhuoc nang xay ra hie mdi sinh hoac vai narn d§.u sau khi sinh rna khong duoc dieu tri kip thoi se dan den kern phat tri~n vg tri tue,

Uu nang tuyen giap lai gay trang thai cang th~ng va co khuynh hudng rai loan tam than nhu lo lang qua muc, hoang tuong.

• Tac dung len chirc nang co,

Tang nhe hormon tuyen giap thuong lam co tang phan ung (vigor) nhung neu hrcng hormon duoc bai tiet qua nhieu co trd nen yeu vi tang thoai hoa protein cua co. Mat khac neu thieu hormon tuyen giap, cd trd nen cham chap nhat la gian rat cham sau khi co.

MQt trong nhirng dau hieu dac trung cua uu nang tuyen giap la run cd. Day khong phai la loai run cd bien dQ ldn nhu run cd cua Parkinson hay run cd do ret rna la loai run cd nhanh nhung nhe vdi t§.n so' 10-15 Ian trong mot phut. Co th~ quan sat hien tuong nay d~ hen khi d~t mot td giay len nhirng ngon tay xoe rong.

Hien tuong run cd co Ie do cac synap cua trung tam dieu hoa truong luc cd d tuy sang duoc hoat hoa qua rmrc.

Run la mot dau hieu quan trong d~ danh gia mire dQ tac dung cua hormon tuyen giap dai vdi h~ than kinh trung uong.

• Tac dung len ngu,

Do hormon tuyen giap c6 tac dung hoat h6a synap nen nhirng nguci bi uu nang tuyen giap thuong rat met nhung lai luon d trong tinh trang bi hung phan nen rat kho ngu.

Nguoc lai nguoi nhuoc nang tuyen giap lai ngu nhieu, co th~ ngu tdi 12-14 gio trong mot ngay.

5.9. TAc Dl)NG LEN CO QUAN SINH Dl)C

D~ co su phat tri~n va hoat dong binh thuong cua cd quan sinh due, tuyen giap can hoat dQng binh thuong.

a nam gidi thieu hormon tuyen giap c6 th~ mat due tinh hoan toan, nhung bai tiet qua nhieu lai gay bat lire.

a nir gioi thieu hormon tuyen giap thuong gay bang kinh, da kinh nhung thira hormon lai gay it kinh hoac vo kinh va giarn due tinh.

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Tac dung cua hormon tuyen giap len chuc nang sinh due khong phai la tac dung d<\lc hieu rna c6 Ie la su phdi hop gitra tac dung kich thich true tiep len chuyen h6a cua tuyen sinh due vdi tac dung kich thich hoac uc che chuc nang sinh due thong qua hormon tuyen yen.

5.10. TAc Dl)NG LEN cAc TUYEN NOI TIET KHAc

Hormon tuyen giap tang mire bai tiet cua hau het cac hormon n9i tiet khac nhung dong thoi ciing lai tang nhu cfru s11 dung hormon cua cac mo.

Vi du: nong d9 thyroxin tang se lam tang rmrc chuyen h6a glucose d khap noi trong co th~ nhung chinh vi the rna n6 cung lam tang nhu cau bai tiet insulin tU tuyen tuy,

Thyroxin lam tang chuyen h6a hormon vo thuong than d gan nen lai lam tang co che dieu hoa nguoc d~ tang san xuat ACTH tu tuyen yen va ket qua cudi cling la tuyen vo thuong than tang bai tiet hormon vo thuong than.

6. DIEU HDA EAI TIET HORMON TUYEN GIAP

• Do nong d9 TSH cua tuyen yen: TSH cua tuyen yen kich thich tuyen giap bai tiet T 3- T 4 do v~y neu TSH tang thi T 3- T 4 se duoc bai tiet nhieu va nguoc lai neu TSH giarn thi T3-T4 se duoc bai tiet it (xem bai Tuyen yen).

• Khi bi lanh hoac stress ndng d9 T3-T4 se duoc bai tiet nhieu.

• Co che tv digu hoa,

- Ndng d9 iod vo co cao trong tuyen giap se trc che bai tiet T3-T4.

,

- Ndng d9 iod hiru co cao dan tdi giam thu nhan iod va do d6 lam giam t6'ng hop T 3- T 4.

~ ",..!"

7. ROI LO~N HO~ T DONG TUYEN GIAP

7.1. UlJ NANG TUYEN GIAp

7.1.1. Cac nguyen rrhan gay cuong g'iap

- a nhirng benh nhan bi budu d9c, ng9 d9c giap, benh Graves (Basedow) thi kich thuoc tuyen giap tang 2-3 Ifrn so voi binh thuong nhung so' luong te bao bi~u mo trong mot nang giap va kha nang bai tiet hormon cua m6i te bao lai tang len rat nhieu Ian.

Digu dac biet la d nhirng benh nhan nay ndrig d9 TSH trong huyet tuong khong nhimg khong tang rna nguoc lai can giarn, Dong thoi nguci ta tim thay nhtrng chat khac c6 nong d9 rat cao trong rnau cua nhfmg benh nhan nay. Ban chat cua nhiing chat nay la globulin mien dich nen chung duoc goi ten la globulin mien dich kich

79

thich tuyen giap - TSI (Thyroid Stimulating Immunoglobulin). TSI giin voi receptor cua TSH d te bao tuyen giap keo dai (12 gio trong khi TSH chi tren 1 gio) va kich thich lien tuc AMP vong nen da lam tang s6 lucng te bao va tang bai tiet hormon (5-15 Ian). Cac khang th~ nay sinh ra nhu mot qua trinh tv mien d~ chong lai chinh tuyen giap,

- U tuyen giap (adenoma); nguyen nhan nay hiern gap hon, Do c6 khoi u phat tri~n tai tuyen giap nen hormon duoc bai tiet qua nhieu, Nang d9 hormon cao da uc che tuyen yen bai tiet TSH nen phan lanh (khong c6 u) cua tuyen giap hau nhu khong hoat dong.

7.1.2. H(>i chtrng cu'dng giap

Nguoi bi h9i chung cuong giap thuong c6 cac bi~u hien nhu budu c{), lai mat (mat kh6 khep mi), tay run, nhip tim nhanh, hay hoi h9P 10 lang, kh6 ngu, sut can, chuyen h6a co sd tang, d9 tap trung 1131 cao, thoi gian phan X:;1 gan g6t giarn, nang d9 hormon T3-T4 tang, nang d9 TSH giarn, nang d9 TSI tang.

Nhin chung cac dau hieu lam sang cua hoi chung cucng giap deu do nang d9 cao T3-T4 gay ra tru trieu chung lai mat.

Dau hieu lai mat chi gap d 1/3 sd benh nhan bi cucng giap. Nguyen nhan lai mat la do su phu ne d mo sau hoc mat va giarn san co ngoai {) mat. Yeu to nao gay ra tinh trang tren cho den nay can chua ro. a nhimg benh nhan nay nguoi ta tim thay cac globulin mien dich va c6 su tucng xirng giira nang d9 cac globulin mien dich nay vdi nang d9 TSI.

Cling nhu nguyen nhan gay cucng giap, trieu chung lai mat c6 Ie cling la mot qua trinh tv mien.

7.2. NHUqc NANG TUYEN GIAp

7.2.1. Nguyen n ha n gay suy giap

Cling nhu cuong giap, nguyen nhan chu yeu gay suy giap cling la ket qua cua cac qua trinh tv mien chi khac la trong trucng hop nay n6 pha huy tuyen giap chu khong kich thich.

Benh nay thucng bat d§.u bang hien tucng viern tuyen giap, sau d6 tuyen giap dan dan bi xo h6a do do giarn chuc nang.

Ngoai nguyen nhan tv mien, suy tuyen giap c6 th~ g~p sau phau thuat ciit bo tuyen giap, sau dieu tri cucng giap bang ph6ng X:;1.

7.2.2. H(>i chirng suy giap

Cac bi~u hien cua suy giap thuong ngucc lai vdi cucng giap, Benh nhan bi suy giap thucng cham chap , nhip tim cham, ngu nhieu va hay buon ngu, chuyen h6a co Sd giarn, giarn chuc nang dinh dudng gay rung t6c, da c6 vay va c6 phu.

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Dau hieu phu cua nguoi suy giap duoc goi la phu niern vi day la dang phu do ir dong mot khoi luong IOn acid hyaluronic va chondroitin sulfat ket hop vdi protein trong khoang ke do do lam tang dich trong khoang ke.

Ngoai cac bi~u hien tren nhirng nguoi bi suy giap c6 th~ bi xo vfra mach do thieu T3-TcI nen lam tang ndng d9 cholesterol trong mau, dac biet nhirng benh nhan bi suy giap th~ Myxedema (thieu hau nhu toan b9 chuc nang tuyen giap) d~ c6 bieu hien nay.

7.3. BI):NH HAN DON

D:ln d9n la mot tinh trang dUQC gay ra do suy giap manh trong thoi ki bao thai, so sinh va tre em. Khi can trong bung me do thai nhan duoc hormon cua me nen thai van c6 th~ phat tri~n binh thuong. Sau khi sinh vai tuan cho den vai nam dau neu khong duoc phat hien va dieu tri kip thoi dua tre se kern phat tri~n ve th~ chat va trf tue.

Neu diroc dieu tri, dua tn~ c6 th~ phat tri~n ve th~ chat binh thuong nhung ve tri tue van cham do cham phat trien, cham phan nhanh, cham myelin hoa cac noron cua he than kinh trung uong (ngoai tru duoc dieu tri rat sdrn ngay vai tuan sau khi sinh)

c'J nhirng dua tre nay, su phat trien cua khung xuong bi uc che manh hen so voi rna mern do do tao ra su mat can doi ve hinh th~. Benh nhan thuong c6 hinh dang thap lun nhung beo, dai khi ludi to den rmrc kh6 nuot, kh6 tho.

7.4. UENH mrou CO DO THlfiu IOD

Nguyen nhan chu yeu la do thieu iod trong thuc an hoac nuoc uong. LUQng iod cung cap hang ngay khong du d~ t6ng hop hormon tuyen giap nhung qua trinh

. ,

t6ng hop thyroglobulin van binh thuong. LUQng hormon duoc bai tiet khong du d~

uc che bai tiet TSH do do nong d9 TSH trong huyet tuong tang lam cho tuyen giap nd to va luong thyroglobulin duoc san xuat ra qua nhieu. Tuyen giap c6 th~ nang tdi 300-500g.

Thoi ky dau cua benh, chirc nang tuyen giap van binh thuong nhung benh keo dai khong duoc dieu tri se dan toi suy giap.

Phong ngua va dieu tri bang each cho udng, an muoi iod, cho tiern dau iod.

8. HORMO~ CALCITONIN

8.1. NGUON GOC, nAN CHAT HOA HQC

Calcitonin do cac te bao canh nang cua tuyen giap bai tiet hoac can duoc goi la te bao C. Day la nhfrng te bao narn d rna ke xen giira cac nang giap, nhung te bao nay chi chiern 0,1% tuyen giap.

Calcitonin la mot polypeptid c6 32 acid arnin voi trong luong phan tu la 3400.

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8.2. T Ac Dl)NG CVA CALCITONIN

Tac dung cua calcitonin la lam giam nong aQ ion Ca ++ trong huyet tuong bang' hai each.

• Tac dung nhanh cua calcitonin la lam giarn hoat dong' cua cac te' bao huy xuong do do chuyen dich su can bang theo hudng lang' dong cac muoi calci d xuong. Tac dung nay dac biet quan trong d nhirng aQng vat con non va tre em vi d hra tu6i nay qua trinh thay a6i trong xuong (gift a lang' dong va tieu huy) thuong xay ra nhanh ch6ng .

• Tac dung thu phat va keo dai hen do la tac dung lam giam hinh thanh cac te' bao huy xuong moi.

Calcitonin cung c6 tac dung dieu hoa tai hap thu ion Ca ++ d ong than va hap thu ion Ca ++ d ruot, tac dung nay yeu va nguoc vdi tac dung cua parathormon cua tuyen can giap.

Vi nhirng tac dung ail trinh bay d tren, calcitonin c6 tac dung lam giarn nong aQ ion Ca ++ huyet tuong nhung tac dung nay rat yeu d nguoi truong thanh vi hai ly do:

• Tac dung giarn nong aQ ion Ca ++ huyet tuong cua calcitonin ail kich thich manh tuyen can giap bai tie't parathormon.

• (} nguci trucng thanh toc aQ a6i mdi xuong hang ngay thuong rat cham,

Do vay tac dung cua calcitonin dac biet c6 y nghla d tre dang len vi n6 lam tang qua trinh lang' dong muoi calci d xuong a~ dap irng vdi toe aQ thay a6i xuong nhanh trong thoi ki dang phat tri~n cua dua tre.

8.3. DIEU HOA BAI TIth CALCITONIN

t

Su bai tie't calcitonin duoc aigu hoa bdi nong aQ ion Ca ++ trong huyet tuong, Khi

nong aQ ion Ca ++ tang khoang 10% thi ngay tire khac calcitonin duoc bai tie't tang gap 2-3 Ian. Tuy nhien co che' nay thuong yeu va xay ra trong mot thoi gian ngan, tac dung manh hen va keo dai hen la tac dung cua parathormon.

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TUYEN THU'QNG TH~N

1. D~C DIEM CAU TA.O

Tuyen thucng than g6m hai tuyen nho narn d phia tren hai than. M6i tuyen nang khoang 4g (Hinh 7-16).

Tuyen thucng than ducc dIU tao bdi hai phan rieng biet la phan vo thucng than va phan tuy thucng than.

tJ{1ng miJ..ch tluJdng tn~n

~> •

Hinli 7-16. Vj tri va sl,l eung dip rruiu eua hai tuye'n tliuang tluin.

Tuy thucng than narn d phan trung tam cua tuyen va chiern khoang 20% trong luong tuyen, C6 th~ coi hai tuy thucng than nhu hai hach giao cam len trong do cac noron mat sci true va trd thanh te bao bai tiet. Chuc nang cua tuy thucng than lien quan vdi hoat dong cua h~ than kinh giao cam, cac hormon cua cluing duoc bai tiet nhieu khi h~ than kinh giao cam bi kich thich. Nhimg hormon nay gay ra cac tac dung giong tac dung cua h~ than kinh giao cam.

Phfrn vo thuong than duoc cau tao bdi ba lap rieng biet do la lap cau, lop b6 va lop luoi (Hinh 7-17).

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Lop c,;;;, (a/dos/erol7 )

fhan

Hinh 7-17. Cfiu tao tuysn. thztc;Jng tluiri

Lop cau la lop te bao rat mong narn d vung ngoai cung cua tuyen. Lop nay bai tiet cac hormon va chuyen h6a muoi nude rna dai dien la aldosteron.

Lop thu hai la ldp b6 narn d giiia va lop ludi nam sat phia trong cung sat phan tuy thucng than. Ca hai lop nay bai tiet cortisol, cac hormon khac thuoc nh6m hormon va chuyen h6a ducng va androgen.

t

Lop cau va hai lop can lai chiu anh hucng cua nhirng yeu to hoan to an khac

nhau. Nhirng yeu to lam tang sinh ldp cau va lam tang bai tiet aldosterone thi hoan toan khong c6 tac dung vdi hai lop kia. Ngucc lai nhfrng yeu to lam tang bai tiet cortisol va androgen thi lai khong anh hucng den lop cau.

Tuyen thucng than tuy nho nhu vay nhung lai la tuyen sinh mang. Tren dong vat thuc nghiern neu nao bo hai phan tuy thucng than, con vat S8 bi roi loan huyet ap mot thoi gian r6i sau do trd lai binh thucng nhung neu dt ba hai phan va thucng than con vat S8 chet trong tinh trang rdi loan dien giai va stress.

2. VO THUONG TH~N

2.1. SINH T6NG HQP HORMON V() THV()NG TH6.N

Cac hormon va thucng than deu la hop chat steroid. Chung deu c6 mdt nhan chung la nhan sterol hay cyclopentanoperhydrophenanthren. Nhan nay g6m ba vong sau canh va met vong narn canh,

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Nluin cyclopentanoperhydrophenanthren

Hormon vo thuong than c6 hai loai cau true:

• M9t loai c6 mach nhanh gdrn hai carbon d vi tri C)7, do la loai 21 carbon. Hfru he't cac steroid - 21 carbon, ngoai mach nhanh con c6 nh6m OH d Cl7 va diroc goi la 17- hydroxycortisol.

• M9t loai c6 nhorn CO hay OH d Cl7, do la loai steroid 19 carbon. Loai steroid- 19C c6 nh6m CO d vi tri C 17 nen diroc goi la 17- cetosteroid.

Hon 30 lcai hormon duoc tach chiet tU tuyen vo thuong than. Tat ca cac hormon nay d~u duoc t6ng hop tu nhfmg mfru acetat theo con duong cholesterol, qua chang trung gian la pregnenolon va progesteron r6i tu do duoc hydroxyl h6a d vi tri Cll. Cl7, c2), d~ tao thanh cac hormon (Sd d6 7-1).

Acetat

1

Cholesterol

1

Pregnenolon

~~

1

17-0H pregrn010n

Dehydrcepi -

Progesteron

androsteron

11 deoxycorticosteron

17-0H progesteron

Testosteron

1

21~ hydroxylase __.: y

21-~ hydroxylase ____.. :

Aldosteron

....

- Cortisol

Estradiol

Sa do' 7-1: Sinh to'ng hap harmon va thuang tluiri

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Dua vao cau tao va tac dung chinh, cac hormon vo thuong than duoc phan thanh 3 nh6m trong do c6 2 nh6m dong vai tro quan trong la nh6m hormon vo chuyen h6a duong rna hormon c6 tac dung quan trong nhat la cortisol va nh6m hormon vo chuyen h6a muoi nude dai dien la aldosteron.

- Nh6m hormon vo chuyen h6a duong g6m:

• Cortisol: tac dung rat manh, chiern 95% t6'ng hoat tinh.

• Corticosteron: tac dung yeu hon cortisol, chiern 4% t6'ng hoat tinh.

• Cortison: la hormon t6'ng hop, tac dung cung manh g:1n nhu cortisol.

• Prednison: la hormon t6'ng hop, tac dung manh gap bon lan cortisol.

• Dexamethason: la hormon t6'ng hop, tac dung manh gap 30 Ian cortisol. - Nh6m hormon vo chuyen h6a muoi nude g6m:

• Aldosteron: tac dung rat manh, chiem 90% t6'ng hoat tinh cua nh6m.

• Desoxycorticosteron: hoat tinh yeu va luong bai tiet rat it.

CH20H I

o C=O

" OH (18) CH

0=

Aldosteron

(21) CH20H I

C=O

OH

Cortisol

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• Corticosteron: c6 tac dung chuyen h6a muoi nude yeu.

• Cortisol: duoc bai tiet mot IUQng len nhung tac dung len chuyen h6a muoi nude rat yeu.

• Cortison: la hormon t6ng hQP, tac dung len chuyen h6a mudi nude yeu,

- Nh6m hormon sinh due: tac dung gicng' cac hormon sinh due c6 nguon goc tu tuyen sinh due, Tuy nhien binh thuong IUQng hormon sinh due do tuyen va thuong than bai tiet ra rat it nen khong dong vai tro quan trong

Nhu vay nhin chung cac hormon thuoc nh6m hormon va chuyen h6a dirong deu co tac dung rat yeu len chuyen h6a muoi mrdc, Tuy nhien khi IUQng hormon cortisol duoc bai tiet qua nhieu cling se gay ra tac dung dang k~ len chuyen h6a muoi nuoc. Rieng dexamethason la loai hormon t6ng hop c6 tac dung rat manh len chuyen h6a dirong (manh gap 30 Ian cortisol) va cac tac dung khac nhung hau nhu khong c6 tac dung tren chuyen h6a muoi nude.

2.2. V!N CHUYEN V A THOAI HOA HORMON vo THlfQNG TH!N

Trong mau cortisol giin chu yeu vdi globulin, phuc hop nay thuong duoc goi la transcortin. Chi mot IUQng nho giin vdi albumin.

94% IUQng cortisol trong mau narn duoi dang ket hQP, chi khoang 6% d dang W do. Khac vci cortisol, aldosteron chi giin long leo vdi protein huyet tuong va khoang 50% narn d dang W do.

Ca hai hormon nay du d dang W do hay ket hop thi deu duoc van chuyen trong toan b9 dich ngoai bao.

G rna dich cortisol tac dung va bi pha huy trong vong 1-2 gid can aldosteron thi trong khoang 30 phut.

,

Cac hormon va thuong than bi thoai h6a chu yeu d gan va tao thanh glucuronid hoac mot IUQng nho narn duoi dang sulfat. Khoang 25% cac dang nay ducc bai tiet qua mat r6i thai ra ngoai theo dirong phan, 75% IUQng can lai Ul:lQC dao thai qua dirong nude ti~u.

Nong' d9 aldosteron trong mau binh thuong khoang 6 ng/dl, rmrc bai tiet trong 24 gio la 150-250 f.!g.

Ncng d9 cortisol khoang 12 ug/dl va rmrc bai tiet trung binh la 15-20 mg/ngay, Tren nguci Vi~t Nam trucng thanh nong d9 cortisol khoang 150-600 nmol/l

(Trinh Minh Chau & CS, Pharn Thi Minh Duc & CS).

2.3. TAc Dl)NG vA DIEU HOA BAI TIET CORTISOL 2.3.1. Tile du ng Ien ehuy~n hoa glueid

• Tang tao dirong mdi d gan (tao glucose tir nguon nguyen lieu la protein va cac chat khac). Mire tang tao dirong mdi dudi tac dung cua cortisol co th~ tang tU 6-10 Ian. Tac dung nay la ket qua cua hai tac dung do cortisol gay ra:

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+ Cortisol lam tang tat ca cac men tham gia trong qua trinh chuyen acid amin thanh glucose d gan.

+ Cortisol lam tang huy dong acid amin tU cac mo ngoai gan rna chu yeu la tU cd vao huyet tucng roi vao gan, do vQ._y thuc diiy qua trinh t9-0 glucose d gan. Ket qua la lam tang du trft glucose d gan.

• Giarn tieu thu glucose d te bao: Cortisol lam giarn nhe mire tieu thu glucose ella te bao khap moi noi trong co thEi. Co che cua hien tucng nay den nay van chua ro. Tuy nhien tren thuc te nguoi ta d3. quan sat thay cortisol lam giarn oxy h6a NADP thanh NAD I rna su thoai h6a glucose chi xay ra khi NADP duoc oxy h6a.

Do mot mat lam tang t9-0 duong moi, mot mat lam giarn tieu thu glucose d te bao nen cortisol c6 tac dung lam tang duong huyet va c6 thEi gay ra dai thao duong. Dai thao duong c6 nguyen nhan tU tuyen thuong than c6 nhieu d~c diEim gidng dai thao duong do nguyen nhan tU tuyen yen. Voi dai thao duong do tuyen thuong than chi can dung mot lucng nho insulin cling du lam giarn nong dQ glucose trong mau. Neu so sanh gift a dai thao duong do tuyen VQ thuong than va dai thao duong do tuyen yen thi 109-i dai thao ducng tuyen yen kern nhay cam voi insulin hon,

2.3.2. 'I'ac du ng H~n chuy~n hoa protein

- Giarn protein cua te bao: M9t trong nhiing tac dung chinh cua cortisol len h~ thong chuyen h6a cua cd thEi do la giarn du trii protein cua tat ca cac te bao trong cd thEi tru te bao gan. 'I'ac dung nay la do cortisol mot mat lam tang thoai h6a protein d te bao mat khac 19-i lam giarn sinh t6ng hop protein.

- Tang van chuyen acid amin vao te bao gan dong thoi lam tang ham lucng cac men tham gia vao qua trinh sinh t6ng hop protein d gan do do cortisol lam tang sli. dung acid amin d te bao gan va gay ra cac tac dung tiep theo nhu:

• Lam tang toc d9 khu amin d te bao gan.

• Lam tang sinh t6ng hop protein d te bao gan.

• Lam tang t9-0 protein huyet tuong.

• Lam tang chuyen acid amin thanh glucose va do d6 tang sinh duong moi.

- Tang nong d9 acid amin huyet tuong dang thoi lam giarn van chuyen acid amin vao te bao tru gan.

2.3.3. 'I'ac d urig len chuy~n h6a lipid

• Tang thoai h6a lipid d cac rno rna do d6 lam tang nang d9 acid beo tv do trong huyet tucng

• Tang oxy h6a acid beo tv do d te bao dEi t9-0 nang luong.

Mac du tac dung cua cortisol la lam tang thoai h6a lipid nhung khi cortisol duoc bai tiet qua nhieu thi 19-i c6 tac dung lam tang lang dong rna va roi 109-n phan bo rna

88

trong co th~. Trong nhfing truong hop nay rna thuong li dong d mat, vung nguc, bung. Co che cho den nay v§.n chua ro, nguoi ta cho ding c6 le do cortisol mot mat lam tang su ngon mieng mat khac kich thich tang bai tiet insulin.

2.3.4. Tac d urig chong stress

Trong tinh trang stress, ngay lap tire nong d9 ACTH tang trong mau, sau d6 vai phiit su bai tiet cortisol cung tang len nho do rna c6 th~ chong lai duoc cac stress va day la tac dung c6 tinh sinh mang.

Nhimg loai stress lam tang nong d9 cortisol thuong gi,ip la chan thuong, nhiem khuan cap, qua n6ng hoac qua lanh, phau thuat, tiem cac chat gay hoai tti duoi da, hau het cac benh gay suy nhuoc (debilitating), su cang thang than kinh qua muc.

Co che chong stress cua cortisol van chua ra. Nguoi ta cho ding c6 Ie cortisol huy dong nhanh ch6ng nguon acid amin va rna du trir d~ cung cap nang lucng va nguyen lieu cho viec t6ng hop cac hop chat khac bao g6m glucose la chat rat can cho moi te bao hoac mot so hop chat nhu purin, pyrimidin, creatin phosphat la nhirng chat rat can cho su duy tri ddi song te bao va sinh san cac te bao moi.

M9t gia thuyet khac lai cho ding cortisol lam tang van chuyen nhanh dich VaG h~ thong mach nen giup co th~ chong lai tinh trang shock.

2.3.5. 'I'ac d urig chong viem

Cortisol c6 tac dung lam giarn tat ca cac giai doan cua qua trinh viern do do c6 tac dung chong viern manh va tren lam sang tac dung nay duoc ling dung nhieu, 'I'ac dung chong viern cua cortisol duoc giai thich bang hai co che' sau:

• Cortisol lam virng ben mang lysosom do do lysosom kh6 phong cang va kh6 vd.

H:lu het cac men phan giai protein duoc giai ph6ng .ra tU rna viern va lam tang phan ling viern deu duoc du trir trong cac lysosom. M9t khi lysosom kho vd thi nhirng san pharn tren se khong duoc bai tiet,

• Cortisol uc che' men phospholipase A2 la men tham gia trong qua trtnh sinh t6ng hop prostaglandin, leukotrien do vay lam giarn phan ling viern boi chinh hai hop chat nay gay ra gian mach, tang nhiet d9, tang tinh tham cua mao mach.

2.3.6. Tac dung chong d] ling

Khi c6 di nguyen xam nhap VaG co th~ (cac di nguyen nay la cac khang nguyen c6 kha nang phan ling mot each di,ic hieu vdi mot loai khang th~ la IgE), phan ling ket hop giira di nguyen va khang th~ xay ra va keo theo mot chudi cac phan ling di ling.

M9t dac tinh dac biet cua IgE la c6 kha nang g:1n manh vdi dudng bao (mastocytes) va bach cau ua toano Khi di nguyen phan ling voi khang th~ IgE, phuc hop nay se g:1n VaG be mat cua dudng bao hoac bach cau ua toan va ngay lap tuc lam thay d6i tinh tham cua mang te bao dudng bao va bach cau ua kiern lam cho cac bach cau nay vd va giai ph6ng cac chat c6 tac dung gian mach, tang tinh tharn cua mao mach nhu histamin.

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Cortisol khong lam anh hudng de'n phan ling ke't hop giiia di nguyen va khang th~ nhung c6 tac dung lic che giai phong histamin va do vay lam giam hien tuong di ling. Tren Him sang, cortisol thuong duoc dung trong cac truong hop bi di ling, ch6ang phan v~.

2.3.7. Tac du ng len te'bao mau va h~ th6ng mi~n d ich

• Lam giarn so hrcng bach cau ua toan va bach d.u lympho.

• Lam giarn kich thudc cac rna lympho trong co th~ nhu giarn kich thudc hach, tuyen uc,

• Lam giarn san xuat lympho T va khang th~ do vay neu dung cortisol keo dai d~ gay nhiern khuan, nguoc lai dung cortisol se lam giarn hien tuong loai bo manh ghep trong trucng hop ghep tim, than va cac rna khac.

• Lam tang san sinh hang cau,

2.3.8. Tac d u ng len cac t.uyen n<}i tie't khac

• Nang de? cortisol tang se lam giarn su chuyen T 4 thanh T 3 va lam tang su chuyen nguoc lai tU T3 thanh T4.

• Cortisol c6 tac dung len s\1 dap ling cua cac te' bao san xuat hormon hudng sinh due cua tuyen yen vdi GnRH cua vung dudi dai do do lam giam n6ng de? hormon sinh due d ca hai gidi,

2.3.9. Cac tac du ng khac,

• Tang bai tiet HCl cua dich vi do vay dung cortisol keo dai c6 th~ gay viem loet da day.

• N6ng dQ cortisol tang c6 th~ lam tang ap hrc nhan cau,

• Khi nang dQ cortisol tang n6 se lic che su hinh thanh xuong bang each giam qua trinh tang sinh te bao, giam sinh tang hop RNA, protein, collagen cua xuong.

2.3.10. Di~u hoa bai tie't cortisol

Cortisol duoc bai tie't nhieu hay it tuy thuoc vao nang dQ ACTH cua tuyen yen, Ne'u nong' dQ ACTH tang thi cortisol se duoc bai tiet nhieu, nguoc lai nang dQ ACTH giarn thi hrcng bai tie'~ cortisol ciing giarn. Nhip bai tie't cortisol tuong ling vdi nhip bai tie't ACTH (xem hinh 7-12 bai Tuyen yen).

2.4. TAc Dl)NG vA DIEU HDA BAITIET ALDOSTERON

2.4.1. Tac d urrg'

Thie'u toan be? hormon va thuong than se dan tdi chet trong vong 3 ngay de'n 2 tuan tru phi nguoi d6 duoc tiep muoi lien tuc hoac tiern hormon va chuyen h6a muoi-mroc.

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Khong c6 hormon vo chuyen h6a muoi-nuoc, nong d9 ion K~ cua dich ngoai bao tang len va ndng d9 Na + va cr lai giarn di, Ket qua la th~ tich dich ngoai bao va mau cling giarn do d6 hru hrong tim giarn. Nhirng rai loan nay se giarn neu nhu cho benh nhan dung aldosteron. Do vay aldosteron cling nhu cortisol (voi tac dung chong stress, dU9C noi la hormon c6 tinh sinh mang,

Tac dung chu yeu cua aldosteron la tac dung len te bao ang than, ngoai ra n6 cling c6 tac dung len ca te bao cua ang tuyen m6 hoi va ang tuyen nude bot. Thong qua tac dung len te bao ang than, aldosteron dong vai tro quan trong trong viec dieu hoa n6ng d9 ion Na + va K+ trong dich ngoai bao.

• Tac dung lam tang tai hap thu ion Na+ va tang bai xuat ion K+ d te bao ang than, Aldosteron khi den te bao ang than dac biet la te bao ang IU9n xa va ang g6p se hoat h6a h~ gien d nhan te bao va lam tang t6ng h9P cac enzym va cac protein van tai, M9t trong nhfing enzym tang met each dac biet d6 la Na +, K+ - ATPase. Men nay la thanh phan chu yeu cua born Na + - K+ d mang day-ben cua te bao ang than do do lam tang tai hap thu ion Na + va tang bai xuat ion K+.

Chinh vi co che' tac dung nhu da trinh bay d tren nen aldasteran khong gay ra tac dung ngay nrc khac rna thuong phai sau 30 phut cac RNA thong tin mdi duoc t6ng h9P va sau 45 phut mire van chuyen ion Na + moi tang va phai sau nhieu gid moi dat hieu qua tai da.

• Tac dung len th~ tich dich ngoai baa va huyet ap dong mach,

Mac du aldosteran c6 tac dung lam tang manh rmrc tai hap thu ion Na + dong than nhung n6ng d9 ion Na + trong dich ngoai bao van chi tang rat it vi khi ion Na + dU9C tai hap thu se tao ra mot lire tharn thau tuong tv dai voi nude lam cha mot IU9ng nude tuong ung dU9C tai hap thu trd lai. Ket 'qua la th~ tich dich ngoai bao tang va khong lam thay d6i nhieu nong d9 ion Na ". Th~ tich dich ngoai baa tang keo dai 1-2 ngay se dan tdi tang huyet ap d9ng mach,

Neu ndng d9 aldasteron tang caa c6 th~ lam tang th~ tich dich ngoai baa tU 5- 15% va tang huyet ap d9ng mach tU 15-25 mmHg.

Nguoc lai khi nong' d9 aldasteran giarn xuong bang khong, mot IU9ng len ion Na + se bi mat qua duong nude ti~u, khong chi the rna ca th~ tich dich ngoai baa cling giarn. Mat khac khi thieu aldasteron, nong d9 ion K+ trang dich ngoai baa se tang caa. Khi K+ tang tu 60-100% tren mire binh thuong thi se gay ng9 d9C tim, co tim khong co duoc do do khong born duoc mau,

• Tac dung cua aldosteron dai voi te baa ang tuyen m6 hoi va ong tuyen nude bot. Tren te baa ang tuyen m6 hoi va ang tuyen nude bot, aldosteran cling lam tang tai hap thu ion Na + va tang bai xuat ion K+. Tac dung nay dac bist quan trong khi co th~ lam viec trong moi truong nong. Nhd c6 aldasteran rna viec mat muoi qua can duong bay hoi m6 hoi se giarn bot.

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2.4.2. Di~u hoa bai tie't

Su dieu hoa bai tiet aldosteron lien quan chat che vdi dieu hoa nong d9 cac chat dien giai, th~ tich dich ngoai bao, th~ tich mau, huyet ap dong' mach,

Mac du aldosteron cling do tuyen va thucng than bai tiet nhung su dieu hoa bai tiet hormon nay hau nhu kh6ng lien quan den ACTH la hormon tham gia dieu hoa bai tiet cac hormon do ldp b6 va ldp ludi san xuat.

Ba yeu to chu yeu tham gia dieu hoa bai tiet aldosteron la:

• Tang nong d9 ion K+ trong dich ngoai bao se lam tang bai tiet aldosteron.

• Tang heat dong' cua h~ thong renin-angiotensin cling lam tang bai tiet aldosteron.

• Tang nong d9 ion Na + trong dich ngoai bao lam giarn nhe nong d9 aldosteron. Trong ba yeu to tren thi nong' dQ ion K+ va he thong renin -angiotensin c6 hieu hrc manh trong dieu hoa bai tiet aldosteron.

Nong d9 ion Kt chi can tang nhe hoac luu luong mau qua than giarn dgu lam tang bai tiet aldosteron len nhieu Ian so vdi binh thuong.

2.5. T Ae Dl)NG eVA ANDROGEN

Hoat tinh sinh hoc cua androgen c6 nguon goc til va thuong than thi rat it.

Chung chi hoat d9ng nhu nhirng tien chat d~ chuyen thanh dang hormon heat dong' trong mau tuan hoan nhu testosteron va dihydrotestosteron.

• 0 nam gidi: Voi chuc nang binh thuong cua tuyen sinh due thi luong testeosteron va dihydrotestosteron c6 nguon goc til va thuong than chi chiern 5% t6ng luong hormon sinh due nam do vay tac dung sinh h9C cua n6 khong dang k~.

o nam trudng thanh, su bai tiet qua mire androgen cua va thuong than khong gay ra bi~u hien lam sang, nhung d tn~ con n6 se lam duong vat to truce tu6i truong thanh, lam phat tri~n cac dac tinh sinh due nam thu phat truce tu6i day thi,

• 0 nir gidi: Trong trudng hop chuc nang cua tuyen sinh due mi binh thuong, luong androgen binh thuong do tuyen va thuong than bai tiet se khong gay bi~u hien bat thuong. Tuy nhien neu tuyen va thuong than bai tiet qua nhieu androgen nhu trong hoi chung Cushing, u tuyen thuong than hoac tang san tuyen thuong than b5m sinh thi se gay hien tuong nam h6a.

3. ruv TRuONG TR~N

3.1. SINH TONG HOP HORMON TVY THVONG TH~N

Cac hormon cua tuy thuong than duoc t6ng hop til L-tyrosin (la mot acid amin c6 trong thuc an) theo so d6 duoi day.

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TB

DDC

L- tyrosin -t> L- DOPA Dopa min

khu carboxyl j

DBB oxy h6a

PNMT

Adrenalin noradrenalin

methyl h6a TB : Tyrosin hydroxylase

DDC : Dopa decarboxylase

DBB : Dopamin P hydroxylase

oxy h6a

PNMT: Phenethanolamin- N- methyl transferase.

So d8 7-2. Sinh t6?ng hap hormon tuy th.uang thtin,

Tren Him sang t;%p hop ba chat dopamin, adrenalin va noadrenalin duoc goi la ca techolamin,

Binh thuong trong mau khoang 80% la adrenalin va 20% la noradrenalin.

3.2. TAc Dl)NG CVA cAc HORMON TVY THUONG TH~N

Adrenalin va noradrenalin trong mau khi duoc dua den cac cd quan dfch chung gay ra cac tac dung hau nhu giong tac dung cua h~ than kinh giao cam. Di~m duy nhat khac do la thoi gian tac dung keo dai til 5-10 plnit vi cac hormon nay thai tnl' cham hen so voi hoat dong cua he than kinh giao cam.

3.2.1. 'I'ac du ng cua adrenalin

• Tren co tim: Lam tim dap nhanh, lam tang hrc co b6p cua co tim.

• Tren mach mau: Lam co mach duoi da, gian mach vanh, mach nao, mach than va mach co van do do lam Lang huyet ap toi da.

• Tren cac co tron khac; Lam gian cd tron ruot non, da con, phe' quan, bang quang, gian dong tit.

• Lam tang rmrc chuyen h6a cua to an bQ cd th~: catecholamin lam tang tieu thu oxy va tang sinh nhiet. Chinh nho tac dung nay rna adrenalin lam tang hoat dong va su hung phan cua cd th~.

• Lam tang phan giai glycogen thanh glucose d gan va cd do d6 tang giai ph6ng glucose vao mau,

3.2.2. 'I'ac du ng cua noradrenalin

Nhin chung noradrenalin c6 tac dung gidng adrenalin nhung tac dung tren mach mau thi manh hen, n6 lam tang ca huyet ap toi da va ca huyet ap toi thieu do lam co mach toan than. Cac tac dung khac nhu tac dung len tim. len cd tron d(tc biet la tac dung len chuyen h6a thi yeu hon adrenalin.

T7 - SLH

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3.3. CO cHE T Ac Dl)NG

Bang 7-3 : Dap ling chon 19C cua catecholamin tai cac rna

Co quan hoac mo Receptor Tilc du ng
ce tim PI Tang hrc co b6p va nhip
M<;lch mau a Co mach
P2 Gian mach
Th~m P Tang giai ph6ng renin
RUQt a, P Giarn van dQng va tang truong hrc co th<1t
T\lY a Giarn bai tiet insulin va glucagon
P Tang bai tiet insulin va glucagon
Gan P Tang phan giai glycogen
Morna P Tang phan giai lipid
Hau het cac rna P Tang tao nang luong
Da a Tang bai tiet m6 hoi
Phe quan P2 Gian phe quan
Tv cung a Co co
P2 Gian co Ciing nhu cac hormon khac, adrenalin va noradrenalin khi den te bao dich, budc dffu tien la gin vdi receptor c6 tren mang te bao dich. Phuc hop hormon-receptor se heat h6a mot chuoi cac phan ling h6a h9C tiep theo xay ra tai bao tuong te bao dich,

, ,

T'ai rna dich c6 hai loai receptor tiep nhan adrenalin va noradrenalin d6 la a

receptor va preceptor. Loai a va P duoc chi a thanh aI, a2, PI, P2.

T'ac dung cua hai hormon nay len receptor d rna dfch khong giong' nhau.

- Noradrenalin kich thich chu yeu len a receptor. Tac dung cua n6 len preceptor rat yeu.

- Adrenalin lai kich thich ca a va preceptor vdi hieu qua tuong duong nhau.

Nhu v:%y tac dung cua hai harmon nay len cac co quan dich phu thuoc vao loai receptor c6 d co quan d6.

3.4. DIEU HOA nAI TIET

Trong dieu kien co sd hai hormon adrenalin va noradrenalin duoc bai tiet it nhung trong tinh trang stress, lanh, duong huyet giarn, huyet ap giarn hoac kich thich h~ giao cam thi tuyen tuy thuong than tang bai tiet ca hai hormon nay.

o nguoi binh thuong trong trang thai nghi ngoi luong adrenalin do tuy thuong than bai tiet khoang 0,2 ug/kg/phiit va 0,05 ug/kg/phut noradrenalin. Vdi luong

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nay huyet ap c6 th~ duoc duy tri a mire binh thuong ngay ca khi d.t dirt toan b9 duong than kinh giao cam den tim.

Nang d9 adrenalin trong rnau a dieu kien cd sa la 170-520 pmol/l, can nang d9 noradrenalin la 0,3 - 28 nmol/l. a nguoi Vi~t Nam (nam 18 - 22 tu5i) nang' dQ catecholamin buci sang (8h 30) la 73,48 ± 27,07 nmol/l (Pham Thi Minh Dire va cs, 1998)

4. R6I LOAN HOAT DONG TUYEN THlJQNG TH~N

4.1. NHUQC NANG TUYEN THUQNG TH~N - BBNH ADDISON

80% truong hop bi Addison la do teo tuyen thuong than tien phat. Co che' benh sinh cua nhiing truong hop nay c6 Ie la do hien tuong tv mien. MQt so' truong hop khac c6 th~ do lao tuyen thuong than hoac do khoi u chen ep,

Bi~u hien cua benh la bi~u hien cua su thieu hai hormon aldosteron va cortisol.

• Do thieu aldosteron: giarn nang dQ ion Na + trong mau, tang nang dQ ion K+ trong mau, giarn th~ tich dich ngcai bao. Vi th~ tich dich ngoai bao giarn, th~ tich huyet tuong giarn nen so hrong hong cau trong mot don vi th~ tich rnau tang len ra ret, luu luong tim giarn va benh nhan se chet trong tinh trang shock sau 4 ngay den 2 tuan neu khcng duoc dieu tri bang aldosteron.

• Do thieu cortisol: giarn nang d9 glucose trong mau, giarn huy dong protein va lipid tu cac rna do do lam giarn nhieu chuc nang chuyen h6a khac cua cd th~. Thien cortisol lam cho cd tra nen yeu, van dong' kern, nguoi met moi va kha nang chong stress kern.

• IT dong sac to' melanin

Ngoai nhirng bi~u hien do thieu aldosteron, thieu 'cortisol nguoi bi benh Addison can c6 bi~u hien r6i loan sac to' a da va niern mac. Nhiing mang sac to' nay thuong xuat hien a nhirng vung da mcng va a vung niern mac,

Nguyen nhan gay ra bi~u hien nay la do luong bai tiet cortisol giarn da gay tac dung dieu hoa nguoc len vung duoi d6i va tuyen yen va lam tang bai tiet ACTH. Chinh hormon ACTH da kich thich san xuat nhieu siic to' melanin va gay ra U dong thanh cac mang sac t6tren da va niern mac,

4.2. HOI CHUNG CUSHING

HQi chirng Cushing la hoi chirng uu nang tuyen vo thuong than do u te baa bai tiet cortisol, u tuyen vo thuong than hoac u te bao bai tiet ACTH cua tuyen yen.

Nguoi bi benh thuong c6 bi~u hien dac biet nhu nguc, bung tren bee, tu chi gay do c6 hien tuong tang huy dong rna a phan thap cd th~ nhung lai gay 11 dong rna a nguc va bung tren, Di kern vdi r6i loan phan b6 rna cua cd th~, nguoi benh con c6 bi~u hien phu dac bi~t th~ hien a mat. Ngtroi benh thtrong c6 khu6n mat cang tron d6i khi c6 mun trung ca. Da d~ nut, co yeu do giarn protein va collagen a da va cd.

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Huyet ap tang dong thoi c6 bi~u hien dai duong. Hfiu het benh nhan c6 bi~u hien loang xuong.

4.3. H()l CHUNG TANG ALDOSTERON TIf~N PH AT

Nguyen nhan cua benh thuong do u te bao lop cau va thuong than, doi khi do tang san te bao bai tiet aldosteron.

Benh duoc bi~u hien bang giarn nang d9 ion K+ trong dich ngoai bao, tang nhe th~ tich dich ngoai bao, th~ tich mau va nang d9 ion Na + d dich ngoai bao, tang huyet ap.

4.4. HQI CHUNG NAM H6A

H9i chung nam h6a la do u va thuong than (u te bao bai tiet androgen).

Benh thuong g~p d tre em hen la nguoi Ion va thuong' g~p d tre trai. Tu 3-4 tu6i tre da c6 cac dau hieu day thi nhu Ion nhanh; co b~p ph at trien; giong n6i 0; moe trung ca, long nach, long mu; duong vat to, tu6i xuong ph at trien nhanh hen so voi tu6i thuc,

4.5. n¢NH TANG SAN THlJ<)NG TH~N BAM SINH (CONGENITAL ADRENAL HYPERPLASIA, CAH)

Benh tang san thuong than barn sinh con diroc goi la h9i chung sinh duc-thuong than. Benh xuat hien do c6 khuyet tat gen gay thieu mot so enzym tham gia trong qua trinh sinh t6ng hop hormon va thuong than trong d6 hay g~p nhat la thieu enzym 21 P hydroxylase.

Do thieu enzyrn 21 P hydroxylase nen khong san xuat duoc cortisol va aldosteron. Nang d9 cortisol giarn da kich thich tuyen yen tang bai tiet ACTH. Dudi tac dung cua ACTH tuyen va thuong than nd to va tang t6ng hop horrnon nhung kh6ng th~ Mng h9P thanh cortisol rna ill theo con duong Mng hop hormon sinh due nam.

Nang d9 androgen tang lam nam h6a cac em gai va day thi sam cac em trai.

4.6. U TIJY THlJ<)NG TH~N

Nguyen nhan la do u cac te bao ua cram cua tuy thuong than (pheochromocytoma).

U tuy thuong than la lcai u lanh tinh nhung neu khong phau thuat cat bo khoi u thi benh nhan c6 th~ chet vi tang huyet ap va suy tim. Cac dau hieu d~ chfrn doan do la nang d9 catecholamin trong mau tang cao va nhin thay khoi u tren sieu am hoac chup dt lop 6 bung.

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TUYEN Tl)Y N(n TIET

1. o~c OlEYl CAU T~O

T\lY noi tiet bao gom cac cau true duoc goi la cac ti~u dao Langerhans. Tuyen tuy d nguoi co chung 1-2 trieu ti~u dao Langerhans, moi ti~u dao duong kinh chi khoang 0,3 mm. Bao quanh ti~u dao co nhieu mao mach (Hinh 7-18).

Moi ti~u dao chua 3 loai te bao chinh la te bao alpha, beta va delta. Nhirng te bao nay duoc phan biet vdi nhau bang cau tao hinh thai va tinh chat biit mau khi nhuorn.

Hinh 7-18. Cau tao cua tuyer: tuy

- Te bao beta chiern 60% t6ng so cac loai te bao. Chung narn d phan giua cua

moi ti~u dao va bai tiet insulin.

- Te bao alpha chiern 25%, bai tiet glucagon.

- Te bao delta chiern khoang 10%, bai tiet somatostatin.

- M9t so it te bao khac duoc goi la te bao PP, chung bai tiet mot hormon chua ra

chuc nang va duoc goi la polypeptid cua tuy.

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