FISIOLOGI GINJAL

Unit 1 - Objective 1

F I S I O L O G I HEWAN II


YANG DIPELAJARI

EKSKRESI---GINJAL + KULIT THERMOREGULASI ENDOKRINOLOGI OTOT REPRODUKSI SARAF


Pustaka : Guyton, Fisiologi manusia dan

mekanisme penyakit Ganong, Review Fisiologi Kedokteran


EKSKRESI? SEKRESI?


GINJALFungsi umum ginjal : mengatur volume cairan badan, tek. osmotik dan

keseimbangan elektrolit pengaturan keseimbangan asam basa pengeluaran zat2 yg tidak berguna ; urea, uric acid penyimpanan substansi energi yg menguntungkan :

glukosa, asam amino detoksifikasi


fungsi endokrin : eritropoetin,renin (??) Pelepasan prostaglandin

menyebabkan pembuluh darah ginjal berdilatasi yang berperan dalam pengaturan aliran darah ke ginjal


Aktivasi vitamin D Vitamin D dibuat di kulit , dirubah menjadi vit D3 oleh

ginjal Vit D3 membantu homeostasis dengan meningkatkan

absorbsi kalsium dari tractus digestivus

Sekresi H+ dan reabsorbsi HCO3-

Eliminasi ion hidrogen yangberlebihan dan conserves zat buffer spt bikarbonat shg dpt mengontrol pH cairan tubuh


Anatomi ginjal

Capsule

Renal VeinRenal ArteryCortex

Pyramid

PapillaCalyx

Pelvis

Ureter

Column

Medulla

Nephron


Fungsi utama ginjal :

Membuat urin, meliputi : ekskresi sisa metabolisme reabsorbsi zat yg msh bermanfaat----Atur

kadar komponen cairan tubuh -----(homeostasis)


Sistem Urinaria

Renal arteryKidney

Ureter

Urinary Bladder

Renal Vein

For sphincters, see nex slide


SISTEM URINARIA

Internal urethral sphincterExternal Urethral Sphincter

Male Sphincters

Female Sphincters


Anatomi faali ginjalterdiri dari nefron : glomerulus tubulus kontortus proximalis ansa henle tubulus kontortus distalis bbrp nefron bermuara pd tub. kolektivus----duktus

kolektivus


NEFRON

Efferent arteriole

Afferent arteriole

Bowman’s capsule

Collecting duct

Proximal convoluted tubuleGlomerulus

Peritubular capillaries

Vasa recta

Decending limb of loop of Henle

Ascending limb of loop of Henle

Distal convoluted tubule



Glomerulus diameter ±200 mikron luas permukaan filtrasi kapiler 1,5 m2 tdr anyaman kapiler diselubungi kantong buntu spt

mangkok ----kapsula bowman permeablitas kapiler tinggi, membrana basalis kapiler

berpori2. arteriola afferen-----anyaman (rete) kapiler---arteriola

efferen scr fungsional hanya dpt dilewati zat diameter < 8 nm pembuatan urin dimulai dlm kapiler glomerulus-----

mjd ultra Filtrat


Glomerulus

Afferent Arteriole

Efferent Arteriole

Bowman’s Capsule

Proximal Convoluted Tubule

Glomerulus


Tubulus konvulatus proksimalis panjang 14 mm, diameter 55 mikron epitel kuboid simplek mpy “brush border” ---mikrovilli banyak mgdg mitokondria (energi utk transpor aktif) Reabsorbsi filtrat : sodium (65%), water (65%),

bicarbonate (90%), chloride (50%), glucose (nearly 100%!), etc

Sekresi obat, sampah dan ion hidrogen



Ansa henle sel epitel sangat tipis pori2 luas, permeabilitas besar ada 2 bagian---masuk medula dsbt

pars descendent, meninggalkan medula pars ascendent---ke korteks---mendekati glomerulus---nampak padat berinti dsbt makula densa-----ke tub. distalis


Afferent Arteriole

Efferent Arteriole

DCT

Macula Densa Cells

Granular Juxtaglomerular (JG) Cells

PCT

Bowman’s Capsule


Tubulus kontortus distalis di korteks tdk py makula densa bermuara pd tub. kolektivus banyak mitokondria di membran basalis


Pembentukan urin Urin : larutan encer mgdg limbah hasil

metabolisme berasal drdarah. Warna kuning---urokrom

Proses pembentukan urin A. filtrasi glomeruli B. reabsorbsi tubulus C. sekresi tubulus


Filtrasi Glomeruli darah dlm kapiler glomeruli dipisahkan dr

cairan filtrat glomeruli dlm kapsula bowman oleh filter yg tdr dr 3 lapisan

1. endotelium kapiler 2. Podocyt 3. epitel pars visceralis kapsula bowman (py

celah diameter 25 nm)


Mekanisme Filtrasi Glomerular

Bowman’s Capsule

Glomerulus

Fenestrated Capillary

Podocyte with Basement Membrane


Aliran darah ginjal(RBF = renal blood flow)

25% dr curah jantung (1200 ml/menit)

Proses filtrasi glomerulus tjd krn adanya: 1. tek. Hidrostatik drh di kapiler glomerulus (pB) 2. tek. Hidrostatik dalam kapsula bowman (pC) 3. tek. Kolloid osmotik protein plasma (pCo)


Gaya Netto

(Effective Filtration Pressure/EFP)

EFP = PB-PC-PCo

EFP = 55-15 -30

= 10 mmHg


Laju Filtrasi Glomerulus (GFR= Glomerulus Filtration Rate) jumlah filtrat yang disaring dari plasma dlm

satu menit mis. GFR 125 ml/mnt---tiap jam 7,5 liter

filtrat---tiap hari 180 liter filtrat Padahal produksi urin ± 1 liter / hari----artinya

99% filtrat direabsorbsi kembali


Tekanan hidrostatik kapiler glomeruli berubah2 tergantung:

vasokontriksi a. afferent—tek. drh glomerulus<< tek. Filtrasi effektif<<

vasokontriksi a. effrent----tek. drh. glomerulus>>tek. Filtrasi effektif>>

vasodilatasi a. afferent----tek. drh glomerulus>> tek. Filtrasi efektif>>

vasodilatasi a. efferent----tek. drh glomerulus << tek. Filtrasi glomerulus <<


Faktor2 yg mempengaruhi GFR

1. Perubahan tekanan hidrostatik dalam kapiler glomeruli

olah raga berat---tek, drh umum meningkat---vasokonstriksi a. aferent (rangsangan sy. Simpatik)-----GFR turun----urin sedikit

-minum kopi---kafein sebabkan vasodilatasi a. afferent---GFR naik---urin banyak


2. Perubahan tekanan hidrostatik kapsula Bowman

obstruksi jalan kencing (mis. : batu ginjal/parasit)---tek. hidrostatik kaps. Bowman meningkat----GFR turun


3. Perubahan tekanan kolloid osmotik plasma

Dehidrasi (minum<<, diare/muntah)---GFR turun

Hiperproteinemia---tek. koloid osmotik plasma meningkat----GFR turun


4. Perubahan permeabilitas membran glomeruli

Penyakit ginjal (mis. : radang)---kapiler glomeruli permeable---protein plasma ikut masuk---proteinuria/albuminuria


5. perubahan luas filtrasi penyakit ginjal + nephrectomy parsial---

rusak glomeruli----luas area berkurang----GFR turun


Mekanisme perpindahan air dan

NaCl


?

?

?

?


Persentase cairan filtrat glomerulus yg direabsorbsi dlm tiap segmen tubulus sbb. :

% Tub. proximalis 65 Lenkung Henle 15 Tub. distalis 10 Duktus kolektivus 9,3 Mengalir sbg urin 0,7


Reabsorbsi air dipengaruhi hormon antidiuretic hormon

(ADH=vasopresin)---hipofisis posterior pembebasan diatur oleh osmoreseptor fungsi meningkatkan permeabilitas tub. thd air----

meningkatkan reabsorbsi air darah encer (mis.banyak minum)---kadar ADH turun----

reabsorbsi air berkurang—urin banyak darah pekat---- (mis. : ???) kadar ADH naik----reabsorbsi

air bertambah----urin sedikit gangguan produksi ADH---produksi air banyak---

diabetes insipidus tekanan osmotik dr isi tubulus---pengaruhi jumlah air yg

diambil-->>garam, gula (diabetes mellitus)


Reabsorbsi Glukosa absorbsi scr transport aktif kemampuan reabsorbsi glukosa oleh sel2 tub. terbatas nilai ambang ginjal= batas kemampuan sel2 tub.

reabsorbsi glukosa scr sempurna contoh : kadar gula nomal mns 60-100mg/100cc jika

kadar glukosa drh 180 mg/100cc( diabetes mellitus)-----sisanya

(80 mg/ 100cc)dibuang bersama urin----glikosuria


Fungsi Juxtaglomerular Apparatus• Memelihara tekanan darah• Jika tekanan darah turun, sel granular JG akan

melepaskan renin Renin

• angiotensinogen angiotensinogen I ACE(angiotensin converting enzime)

angiotensinogen I angitensinogen II

vasokonstriktor

tekanan darah

Unit 1 - Objective 6Granular juxtaglomerular cell


Angiotensin II jg menstimuli pelepasan aldosteron dr adrenal korteks

Aldosteron menstimuli tub. Konvul. Distalis utk mengabsorbsi NaCl

Reabsorbsi garam menyebabkan air akan berpindah ke darah, meningkatkan volume shingga meningkatkan tekanan darah.



makula densa cells akan memonitor kandungan garam dalam darah

Jika kandungan garam terlalu tinggi , makula densa sel akan menghambat sel granular dan menekan pelepasan renin


Makula densa


Penekanan renin beraksi sbagi mekanisme feedback negatif yg mencegah peningkatan angiotensin II, aldosteron dan tekanan darah



The Counter Current Mechanism We will begin our discussion of the counter current mechanism with the ascending limb of the loop of Henle (ALLH). This portion of the nephron reabsorbs chloride by active transport. As chloride moves from the filtrate it pulls along sodium into the interstitium of the medulla. The medulla then becomes very hyperosmotic



The Counter Current MechanismAs salt (NaCl) leaves the ALLH, the osmolarity of the fluid decreases from 1,200 to 100 milliosmoles/L (mOSM/L). This happens because the ALLH is impermeable to water. The net effect of this activity is to remove salt from the kidney filtrate and transfer it into the medulla where it can be saved for use by the body.



The Counter Current MechanismThe accumulated salt in the interstitium of the medulla acts as an osmotic force which can be used to “draw” and conserve water from other parts of the nephron: the decending limb of the Loop of Henle (DLLH) and the collecting duct. The DLLH is a thin passive segment that is permeable to water, but, impermeable to salt.



The Counter Current MechanismAs the DLLH gives up water to the medullary interstitium, the osmolarity of the fluid changes from 300 to 1,200 mOSM/L. The net effect of this process is to conserve water for the body. Thus, the loop of Henle actively transfers salt back into the kidney which can be used to save water osmotically. A remarkable process!



The Counter Current MechanismThe hyperosmotic interstitium of the medulla will also “pull” and conserve water from the collecting duct, but, on a variable basis depending on the availibility of ADH. As water moves from the collecting duct, urea will follow. Thus, as water is conserved at this level, a certain amount of urea is also conserved. The urea contributes to the high osmolarity of the medulla



The Counter Current MechanismThe availibility of Antidiurectic Hormone (ADH) is determined by dehydration and thirst. Under these conditions, the hypothalamus makes extra ADH and stores it in the posterior pituitary where it can be released. The increased release of ADH causes the “water pores” of of the collecting duct to open and allow water to move from the urine to the medulla.



The Counter Current MechanismAs water leaves the collecting duct, the urine becomes progressively more concentrate. The osmolarity of the collecting duct fluid will increase from about 150-300 to 1,200 mOsm/l. under these conditions. If ADH is not present, water is not conserved and is lost as part of a dilute urine (100 mOsm/l).



The Counter Current MechanismThe vasa recta is made up of a group of capillary like vessels and is freely permeable to salt and water. The vessels of the vasa recta roughly flow counter to the loop of Henle and acts as a counter current exchanger. As blood flows through the vasa recta it picks up water and leaves behind salt. Thus, the vasa recta returns conserved water back to the body and leaves the salt which maintains the hyperosmotic medulla.



Objective 8If the kidneys filter 16 grams of NaCl per day and then reabsorb 14 grams of NaCl per day, then 2 grams of NaCl would be excreted or eliminated by the kidneys per day as part of the urine.

Amount Excreted = Amount Filtered - Amount Reabsorbed

2 g NaCl/day = 16 g NaCl/day - 14 g NaCl/day



Objective 8Examine the following and find the missing value: Amount Excreted = Amount Filtered - Amount Reabsorbed

1) ? = 100 g of glucose - 100 g of glucose

2) 100 g of glucose = ? - 300 g of glucose

3) 100 g of glucose = 400 g of glucose - ?

Answers: (1)equals zero; (2) equals 400; (3) equals 300



Plasma Clearance

Plasma clearance is defined as the amount of plasma that is cleared or “cleansed” of a particular substance in one minute. The kidneys will carry out this clearance process through the use of filtration, reabsorption and secretion.



Plasma ClearanceFiltration will directly affect clearance. As filtration increases, more material will be removed from the blood plasma. Reabsorption will indirectly affect clearance. As reabsorption increases, less material will be removed from the blood plasma. Secretion will directly affect clearance. As secretion increases, more material will be removed from blood plasma.



Plasma Clearance

The formula used to calculate plasma clearance is: C = V x U/P

C = plasma clearance rate in ml/min

V = urine production rate in ml/min

U = the concentration of a substance in the urine in mg/ml

P = the concentration of a substance in the plasma in mg/ml

As you track the units in the equation, you will notice that mg/ml cancel out, leaving ml/min.



Plasma Clearance

Let us practice calculating plasma clearance using the clearance equation. In all your calculations, assume that the urine production rate (V) is 2 ml/min. Let’s start with the substance inulin (not insulin!). If after a dose of inulin, your urine has 30 mg/ml and your plasma has 0.5 mg/ml of this substance, what is the inulin clearance rate? If you got 120ml/min, you are correct!



Plasma Clearance

If you did not get 120ml/min, look at the following calculation and recheck your work.

120 ml/min = 2 ml/min x 30 mg/ml/ 0.5 mg/ml



Plasma ClearanceTest your ability to conduct further calculations by calculating the clearance rate for the following substances:Substance Urine concentration Plasma concentration

Urea 7.0 mg/ml 0.2 mg/ml

Glucose 0.0 mg/ml 1.0 mg/ml

Penicillin 298 mg/ml 0.7 mg/ml

Remember that the urine production rate (2ml/min) will be the same for all of the above calculations. The clearance rate for each of the above substances will be: Urea = 70 ml/min; Glucose = 0 ml/min; Penicillin = 851 ml/min. Were you able to get the right answers? If not, go back and restudy the clearance process.



Dialysis Therapy

Dialysis is a process that artificially removes metabolic wastes from the blood in order to compensate for kidney (renal) failure. Kidney failure results in the rapid accumulation of nitrogen waste (urea, etc.) which leads to azotemia. Uremia and ion disturbances can also occur. This condition can cause acidosis, labored breathing, convulsions, coma and death.


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FISIOLOGI GINJAL