SISTEM EKSKRESI

Urinary System

• “Filtering” of the Blood

• Electrolyte Regulation

• pH Regulation

• Regulation of Blood Volume

• Stimulation of Erythropoiesis

• Vitamin D Synthesis

Components And Functions

Two kidneys, which remove dissolved waste and excess substances from the blood and form urine. The kidneys regulate the extracellular fluid environment by making urine from plasma. By doing this the kidneys also regulate:

– Blood plasma volume– Concentration of waste products in the blood– Plasma pH

– Concentration of electrolytes (e.g. K+, Cl-, HCO3-) in the blood..

Two ureters, which transport urine from the kidneys to

The urinary bladder, which acts as a reservoir for urine

The urethra, the duct through which urine from the bladder flows to the outside of the body during urination

Systemic Anatomy Overview

How the kidney functions to maintain homeostasis in the body

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Kidney Anatomy

External Anatomy

Renal capsule

Adipose capsule

Renal fascia

Internal AnatomyRenal pelvis, branches into major calyces and minor calyces

Renal medulla, consists of 8-18 renal pyramids (tubulus and collecting ducts of the nephrons)

Renal cortex, divided into the outer cortical region (renal columns) and the inner juxtamedullary

Internal Structure of The KidneyInternal Structure of The Kidney

Blood flow

Nephron

Nephron… the histological and functional unit of the kidney

Each nephron is an independent urine making unit

~ 1.3 million nephrons per kidney

~ 50-55mm in length

Two types of nephrons : Cortical (found in the outer 2/3

of the cortex) and Juxtamedullary nephrons (found at the cortex/medulla junction, Fewer in number, Very long loops of

Henle to make concentrated urine)

Two types of NephronsTwo types of Nephrons

Juxtaglomerular Apparatus

The Component of Nephron

Nephron consists of a Tubular and a vascular component

The tubular component : the glomerular capsule and excretory tubules (proximal convoluted tubule, loop of the nephron, distal convoluted tubule)

The vascular component is made up of blood vessels : the glomerulus and the peritubular capillaries, which surround the excretory tubules

Nephron Histology I

Nephron Histology II

Glomerular (Bowman’s) capsule

Always located in the cortex of the kidney

The inner and outer walls form a cavity called the capsular space

The outer layer is the parietal layer, epithelial cells

The inner layer is the visceral layer, specialized epithelial cells called podocytes which surround the glomerular capillaries

The Glomerular Histology I

The Glomerular Histology II

PodocytesThe spaces between the pedicels provide a passageway for materials to enter the nephron (except proteins which are not filtered out of the blood).

Physiology of The Kidney

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Glomerular Filtration

Tubular Reabsorption

Tubular Secretion

The kidneys filter blood

Useful subtances such as H2O, Na+, glucose and

amino acids are returned to the blood

Products such as K+, H+, certain drugs and organic

compounds may be excreted

Glomerular Filtration

Filtration Barrier

Filtration Pressure– ~ 75 mm Hg– Function of BP

GCP : Glomerular capsule pressureCOP : Colloidal osmotic pressure

Permeable to water and compounds with low molecular weights

Small molecules pass through the pores (fenestration)

of the endothelium

The basement membran (basal lamina)

The filtration slits of the visceral layer of the glomerular capsule and the podocytes

Normally, none of the blood cells can pass through this barrier, include protein molecule

The high hydrostatic pressure of the blood in the glomerulus is primarily responsible for the production of the glomerular (ultra)filtrate.– GFR is ~ 120 ml/min = ~ 180 L/day

Vasoconstriction or vasodilation of glomerular afferent arterioles affects the rate of blood flow and, therefore, affects the GFR.– blood flow = GFR– blood flow = GFR..

Changes in blood pressure don’t affect GFR except in the extreme. – As blood pressure rises, the afferent

arterioles constrict to maintain appropriate blood pressure..

Factors affecting the glomerular filtration rate

Effective filtration rate

Stress

Total surface area available for filtration

Capillary permeability

Intrinsic renal autoregulation

Release of renin

Effective filtration pressure

The GFR increases when the effective filtration pressure in glomerulus increases, and decreases when the pressure decreases

FPeff is determined by the Starling-Landis equation :

Normal : 25 mmHg

FPeff =capsular

hydrostatic pressure

glomerular blood

hydrostatic pressure

_ Oncotic pressure of the blood in the

glomerulus

+

75 20 30

Stress : Sympathetic Regulation of GFR

Stimulates vasoconstriction of afferent arterioles.– Preserves blood

volume to muscles and heart.

Cardiovascular shock:– Decreases

glomerular capillary hydrostatic pressure.

– Decreases urine output (UO).

Intrinsic : Renal Autoregulation of GFR

Ability of kidney to maintain a constant GFR under systemic changes.– Achieved through effects of locally produced chemicals on

the afferent arterioles.

When MAP drops to 70 mm Hg, afferent arteriole dilates.When MAP increases, vasoconstrict afferent arterioles.Tubuloglomerular feedback:– Increased flow of filtrate sensed by macula densa cells in

thick ascending LH.• Signals afferent arterioles to constrict..

Renin-Angiotension-Aldosterone System

Tubular ReabsorptionAbout 99% of the filtrate is reabsorbed.

Water can only be reabsorbed by osmosis.– There are no water pumps.– Because the osmotic pressure of the filtrate is

about the same as plasma, ~ 300 mOsm, ions must be transported to affect the osmotic pressures.

– Na+ diffuses into the cuboidal tubular cells at the apical surface from the filtrate.

• Glucose is frequently cotransported with Na+..

– The Na+ is then pumped by active transport into the surrounding tissue fluid.

• Na+/K+ pumps are only located at the basal and lateral surfaces.

– Cl- ions then follow the Na+ by diffusion into the cell.

– The NaCl creates an osmotic gradient and water flows by osmosis out of the filtrate and into the tissue fluid.

About 85% of salts and water are reabsorbed in the early regions of the nephron..

The composition of the filtrate is fine tuned in the remaining areas of the nephron.

In the loop of Henle, more materials are reabsorbed from the filtrate into the tissue fluid then blood.– In the thick portion of the ascending limb, Na+

diffuses from the filtrate into the cells at the apical surface.

– At the same time K+ and Cl- are actively transported into the cell at the apical surface..

– Na+ is then actively transported across the basal and lateral surfaces into the tissue fluid (blood) by Na+/K+ pumps in the membrane.

– Cl- passively follows the Na+ out of the cell and into the tissue fluid.

– K+ diffuses back into the filtrate and the tissue fluid..

The Countercurrent Multiplier System• The ascending limb is impermeable to water.

– This results in decreasing solute concentration of the filtrate (decreasing osmolality) and increasing solute concentration of the surrounding tissue fluid (increasing osmolality)..

• The descending limb of the loop of Henle is permeable to water but (probably) im-permeable to NaCl.

• Because of the actions of the ascending limb the tissue fluid surrounding this region of the nephron is hypertonic.– Therefore, water moves by osmosis from the

filtrate in the descending limb into the tissue fluid..

Urea also contributes to the high osmolality of the tissue fluid surrounding the loop of Henle.

Urea can diffuse out of the collecting duct into the tissue fluid then back into the ascending limb.

The urea is then transported into the filtrate where it diffuses out through the collecting duct wall and into the tissue fluid, then back into the ascending limb, etc..

Osmolarity of extracellular fluid (mOsm/L)

300

400

600

900

1,200

Osmolarity of extracellular fluid (mOsm/L)

300

400

600

900

1,200

In the collecting ducts, the remainder of the water is reabsorbed from the filtrate into the tissue fluid then the blood.

The medullary regions of the collecting ducts are impermeable to NaCl in the surrounding tissue fluid, therefore, water diffuses out of the collecting ducts.

The water moves through water channels produced from aquaporin proteins.

The number of water channels is influenced by ADH.

Stimulates fusion of vesicles with plasma membrane.

Incorporates water channels into plasma membrane..

Tulular Load

• …amount of a substance passing the filtration membrane per minute

• Tubular Maximum…the maximum rate at which a substance can be reabsorbed

• Spillage

Tubular Secretion

COMPARISON OF FILTRATION, COMPARISON OF FILTRATION, REABSORPTION, EXCRETIONREABSORPTION, EXCRETION

SUBSTANCESUBSTANCEAMOUNT FILTERED AMOUNT FILTERED

BY GLOMERULI BY GLOMERULI (DAILY)(DAILY)

AMOUNT EXCRETED AMOUNT EXCRETED IN URINE IN URINE

(DAILY)(DAILY)

PERCENTAGE PERCENTAGE REABSORBED REABSORBED BY NEPHRON BY NEPHRON

TUBULES TUBULES

GlucoseWaterCalciumSaltPhosphateUreaSulfate

170.0 g150.0 L

17.0 g700.0 g

5.1 g50.0 g

3.4 g

100.099.098.898.080.040.033.0

0.0 g1.5 L0.2 g15.0 g1.2 g30.0 g2.7 g

Ureters

• Uroliths

Accessory excretory structures

Urinary Bladder

• Trigone

• Cystitis

Accessory excretory structures

Urine Production

Urine is created in– renal cortex– and renal

medulla

Drains out end of renal papilla,

into renal pelvis,

into ureter,

and then into the bladder

Renal Flow Rates

Prime Regulators

• ADH / Antidiuretic Hormone– Posterior pituitary– Diabetes insipidus – insufficient ADH /

dilute urine

• Renin-Angiotensin-Aldosterone– Adrenal Cortex– Associated with BP Regulation

Production of Vit DProduction of Vit D33

Electrolyte and Acid/Base Electrolyte and Acid/Base BalanceBalance

Kidneys regulate NaKidneys regulate Na++, K, K++, H, H++, Cl, Cl--, HC0, HC033--, ,

and POand PO443-3-..

Control of plasma NaControl of plasma Na++ is important in is important in regulation of blood volume and pressure.regulation of blood volume and pressure.

Control of plasma of KControl of plasma of K++ important in important in proper function of cardiac and skeletal proper function of cardiac and skeletal muscles.muscles.– Match ingestion with urinary excretion..Match ingestion with urinary excretion..

In DCT and CCD, the remaining NaIn DCT and CCD, the remaining Na++ and K and K++ is is reabsorbed under the influence of reabsorbed under the influence of aldosteronealdosterone..– AldosteroneAldosterone is the principal mineralocorticoid is the principal mineralocorticoid

(secreted by ?)(secreted by ?)– AldosteroneAldosterone stimulate the reabsorption of Na stimulate the reabsorption of Na++ in in

exchange for Kexchange for K++ -- therefore, -- therefore, K+ is excretedK+ is excreted..

In the absence of aldosteroneIn the absence of aldosterone, ~ 2% of Na, ~ 2% of Na++ is is excreted and 100% of Kexcreted and 100% of K++ is reabsorbed. is reabsorbed.

When aldosterone is secreted in max. amountsWhen aldosterone is secreted in max. amounts, , 100% of Na+ is reabsorbed and > 50% of K100% of Na+ is reabsorbed and > 50% of K++ is is excreted.excreted.– KK++ can only be secreted in the urine in the presence can only be secreted in the urine in the presence

of aldosterone..of aldosterone..

Aldosterone secretion is regulated by Aldosterone secretion is regulated by negative feedback of blood [K+] & [Na+].negative feedback of blood [K+] & [Na+].

RiseRise in [K+] in [K+] directlydirectly stimulates aldosterone stimulates aldosterone secretion.secretion.– The more aldosterone secreted, the more K+ The more aldosterone secreted, the more K+

secreted into the filtrate and therefore secreted into the filtrate and therefore excreted from the body.excreted from the body.

DropDrop in [Na+] in [Na+] indirectlyindirectly stimulates the stimulates the secretion of aldosterone.secretion of aldosterone.– ↓ ↓ [Na+] stimulates renin secretion from [Na+] stimulates renin secretion from

granular cells of the juxtaglomerular granular cells of the juxtaglomerular apparatus..apparatus..

– ReninRenin (an enzyme) converts (an enzyme) converts angiotensinogen into angiotensin I.angiotensinogen into angiotensin I.

– Angiotensin IAngiotensin I is then converted into is then converted into angiotensin II by angiotensin-converting angiotensin II by angiotensin-converting enzyme (ACE).enzyme (ACE).

– Angiotensin IIAngiotensin II stimulates aldosterone stimulates aldosterone secretion (and a rise in blood pressure).secretion (and a rise in blood pressure). Powerful vasoconstrictor.Powerful vasoconstrictor. Stimulates thirst..Stimulates thirst..

Renin-Angiotension-Aldosterone System

Atrial natriuretic peptide, secreted by Atrial natriuretic peptide, secreted by the atria of the heart, stimulates the the atria of the heart, stimulates the kidneys to excrete more Na+.kidneys to excrete more Na+.

Water then follows the Na+ by osmosis.Water then follows the Na+ by osmosis. This lowers the blood volume (& blood This lowers the blood volume (& blood

pressure)..pressure)..