FISIOLOGI GINJAL

Topik
• 1. The body fluid compartments
• 2. Glomerular Filtration, Renal blood flow, and their control
• 3. Tubular reabsorption and secretion
• 4. Urine concentration and dilution; Regulation of extracellular fluid
osmolarity and sodium concentration
• 5. Renal regulation of K, Ca, PO4, and Mg; Integration of renal
mechanisms for control of blood volume and extracellular fluid
volume
• 6. Acid-base regulation
• 7. Diuretics
The Body Fluid Compartments
Fluid Balance
Fluid volumes
Ionic composition of fluids
Transfer of fluid
• Between plasma and interstitial: depends on hydrostatic and colloid
osmotic forces/oncotic force

• Between intracellular and extracellular: depends on osmosis, which

depends on the concentration of small electrolytes such as sodium
and chloride
• Hydrostatic force?

• Oncotic force?

• Osmosis?

• Osmole? Molarity? Molality? Mole?

• Iso/Hypo/Hypertonic

• Iso/Hypo/Hyperosmotic
Effects of fluids to body
Edema
• Edema refers to the presence of excess fluid in the body tissues

• Intracellular edema / non-pitting edema

• Hyponatremia
• Depression of metabolic systems of the tissues
• Inadequate nutrition to the cells

• Extracellular edema / pitting edema

• Abnormal leakage of fluid
• Lymphatics failure
Causes of extracellular edema
Factors preventing Edema
• Low compliance of the interstitium
• Ability of lymph flow to increase 10-50x
• Washdown of interstitial fluid protein concentration
Urine Formation
Functions of kidney
• Excretion of metabolic waste products and foreign chemicals
• Regulation of water and electrolyte balances
• Regulation of body fluid osmolality and electrolyte concentrations
• Regulation of arterial pressure
• Regulation of acid-base balance
• Regulation of erythrocyte production
• Secretion, metabolism, and excretion of hormones
• Gluconeogenesis
Metabolic waste
• Urea
• Creatinine
• Uric acid
• End products of hemoglobin breakdown
• Metabolites of various hormones
• Nephron:
• Cortical
• Juxtamedullary
• Memiliki vasa recta, berperan lebih penting dalam proses konsentrasi urine
Glomerular Function, Renal Blood
Flow, and Their Control
Glomerular Filtration Rate
• Glomerular filtration amounts up to 180 liters each day

• 20% of plasma flowing through the kidney is filtered through the

glomerular capillaries

• Glomerular filtrate’s composition is similar to plasma’s except that it

has no protein and cellular components.
Determinants of GFR
• Glomerular hydrostatic pressure is determined by:
• Arterial pressure
• Afferent arteriolar resistance
• Efferent arteriolar resistance

• Glomerular capillary colloid osmotic pressure is determined by:

• Arterial plasma colloid osmotic pressure
• Filtration fraction
Physiological control of GFR and Renal Blood
Flow
1. Strong activation of sympathetic nervous system decreases GFR
2. Hormonal and autacoid control of renal circulation
1. Angiotensin II preferentially constricts efferent arterioles in most
physiological conditions, due to
2. Vasodilating effects of prostaglandins and bradykinin on afferent arteriole
3. Nitric Oxide decreases renal vascular resistance and increases GFR
AUTOREGULATION OF KIDNEY
• Autoregulation of kidneys refers to the mechanisms by which renal
blood flow and GFR remain relatively constant despite changes in
arterial pressure

• These mechanisms are completely intrinsic to kidney

Tubular Reabsorption and
Secretion
Mechanisms of transport
• Active transport
• Primary
• Secondary
• Pinocytosis (proteins)
• Osmosis
• Diffusion
• Facillitated diffusion
Contoh Primary Active Transport: Natrium
Reabsorption
Contoh Secondary Active transport: Glucose
Reabsorption
Contoh Secondary Active transport: Hydrogen
Secretion
Pinocytosis is a type of endocytosis
• Due to the utilization of enzymes and carrier proteins, active
transport systems have transport maximum
• Transport maximum is the limit to the rate at which the solute can be
transported
Contoh transport maximum: glucose
reabsorption
Osmosis
• In the more distal parts of the nephron, beginning in the loop of
Henle and extending through the collecting tubule, the tight junctions
become far less permeable to water and solutes and the epithelial
cells also have a greatly decreased membrane surface area.
• Therefore, water cannot move easily across the tight junctions of the
tubular membrane by osmosis.
• However, antidiuretic hormone (ADH) greatly increases the water
permeability in the distal and collecting tubules.
Proximal Tubule
• Organic acid and bases:
• Bile salts
• Oxalate
• Urate
• Catecholamines
• Etc.
Loop of Henle
• Consists of 3 functionally distinct segments:
• Thin descending limb
• Thin ascending limb
• Thick ascending limb

• Thin part has no brush borders, few mitochondria, and minimal

metabolic activity
• The descending part of the thin segment is highly permeable to water
and moderately permeable to most solutes, including urea and
sodium.
• The function of this nephron segment is mainly to allow simple
diffusion of substances through its walls.
• The ascending part is virtually impermeable to water

• Thick ascending limb has high metabolic activity and high capacity to
reabsorb Natrium, Chloride, and Potassium (25% of filtered load)

• There is also a significant paracellular reabsorption of cations such as

Mg, Ca, Na, and K as a result of the slight positive charge of tubular
lumen
Distal tubule
• Early part -> macula densa

• The next part of the distal tubule is highly convoluted and has many
of the same reabsorptive characteristics of the thick segment of the
ascending limb of the loop of Henle. That is, it avidly reabsorbs most
of the ions, including sodium, potassium, and chloride, but is virtually
impermeable to water and urea. For this reason, it is referred to as
the diluting segment because it also dilutes the tubular fluid.
• The second half of the distal tubule and the subsequent cortical
collecting tubule have similar functional characteristics.
• Anatomically, they are composed of two distinct cell types, the
principal cells and intercalated cells
• Principal cells reabsorb sodium and secrete potassium
• Depends on the activity of Na/K-ATPase
• Intercalated cells secrete or reabsorb hydrogen, bicarbonate, and
potassium ions

• There are 2 types of intercalated cells:

• Type A secretes hydrogen by hydrogen-ATPase and hydrogen-
potassium/ATPase, and reabsorbs bicarbonate
• Type B reabsorbs hydrogen and secretes bicarbonate
Potassium-sparing diuretics
Medullary collecting duct
• Permeability to water is controlled by ADH

• Permeable to urea and has special urea transporters

• Has capability to secrete hydrogen ions

Summary
Regulation of Tubular
Reabsorption
• Nervous control
• Hormonal control
• Local control

• Reabsorption of some solutes can be regulated independently of

others, especially through hormonal control mechanisms
Glomerulotubular Balance
• There is an intrinsic ability of the tubules to increase their
reabsorption rate in response to increased tubular load

• The precise mechanisms are not fully understood

Peritubular capillary and renal interstitial fluid
physical forces
Pressure Diuresis and Pressure Natriuresis
• Small increases in arterial pressure can cause marked increases in
urinary excretion of sodium and water. However, normally, due to
autoregulation of glomerular flow, increasing arterial pressure
between the limits of 75 and 160 mmHg usually has only a small
effect on renal blood flow and GFR.

• When GFR autoregulation is impaired, as often occurs in kidney

diseases, increases in arterial pressure can cause much larger
increases in the GFR
Mechanisms of Pressure Diuresis and
Natriuresis
1. Increased arterial pressure increases GFR
2. Increased arterial pressure -> increased peritubular capillaries
hydrostatic pressure -> Increased renal interstitial fluid hydrostatic
pressure -> Decreased sodium and water reabsorption -> Increased
urine output
3. Increased arterial pressure -> reduced Angiotensin II formation ->
reduced sodium reabsorption
Hormonal control of tubular reabsorption
Aldosterone
• Effects: Increased sodium reabsorption, increased potassium and
hydrogen excretion
• Mainly works on the principal cells of cortical collecting tubules
• Stimulus:
• Increased extracellular K+ concentration
• Increased Angiotensin II
• Effects:
• Increased stimulation of sodium-potassium-ATPase on the basolateral side of
the cortical collecting tubule membrane
• Increased sodium permeability on the luminal side of the membrane
Angiotensin II
• Is arguably the most powerful sodium-retaining hormone
• Angiotensin II effects:
• Stimulates aldosterone secretion
• Increases resistance of efferent arteriole, which
• Reduces peritubular capillary hydrostatic pressure
• Increases Filtration Fraction therefore increasing peritubular capillary oncotic pressure
• Directly stimulates sodium reabsorption in the proximal tubules, loop of
Henle, distal tubules, and the collecting tubules
Antidiuretic Hormone (ADH)
• Increases water permeability in
the late distal tubules,
collecting tubules, and
collecting ducts.
• This occurs by increasing
migration of Aquaporin-2 to the
luminal membrane, allowing
rapid diffusion of water into the
cell.
• ADH secretion is stimulated by
• Low blood volume
• Low blood pressure

• Stimulus for ADH secretion comes from:

• Osmoreceptors in/around the hypothalamus
• Baroreceptor (carotid, aortic, pulmonary)
• Stretch receptors (cardiac atria)
Atrial Natriuretic Peptide
• Secreted by cardiac atrial cells when they are stretched due to
increased atrial blood pressure and plasma volume expansion

• Effects:
• Reduced renin, and therefore Angiotensin II secretion
• Reduced Na+ reabsorption
Parathyroid Hormones
• Increase tubular reabsorption of calcium especially in the distal
tubules
• Inhibition of Phosphate reabsorption in the proximal tubules
• Increase Magnesium reabsorption in the loops of Henle

• Discussed further later

Sympathetic Nervous System
• Increases sodium reabsorption in the proximal tubule, thick ascend
limb of loop of Henle, and perhaps distal tubules

• Also increases renin and angiotensin II release

Urine Concentration and Dilution;
Regulation of Extracellular Fluid
Osmolarity and
Sodium Concentration
• Extracellular Fluid osmolarity must be regulated precisely so as to
prevent cells from swelling or shrinking due to osmosis.

• Osmolarity is determined by the amount of solute divided by volume

of liquid, therefore, extracellular fluid osmolarity is largely affected by
sodium chloride
• What will be covered in this section:
• Urine dilution
• Urine concentration
• Renal feedback mechanisms that control extracellular fluid sodium
concentration and osmolarity
• Thirst and salt appetite mechanisms
Urine Dilution
• Mechanism:
• Reabsorption of solutes from the distal segments of nephron while failing to
reabsorb water

• ADH has a vital role in diluting urine

Urine Concentration
• Obligatory urine volume is the least amount of urine that has to be
excreted so as to rid excess solutes from the body
• It is affected by the kidney’s maximum concentrating capability

• Urine concentration requires 2 things to happen:

• A high level of ADH
• A high osmolarity of the renal medullary interstitial fluid
• Achieved by countercurrent multiplier mechanism
Countercurrent Multiplier Mechanism
• The osmolarity of the interstitial fluid in the medulla of kidney is
much higher than in other parts of the body

• The major factors that contribute to this:

• Reabsorption of solutes in the thick ascending limb
• Active reabsorption of solutes from the collecting ducts
• Facillitated diffusion of urea from the inner medullary collecting ducts into
the medullary interstitium
• Diffusion of only small amount of water from the medullary tubules into the
medullary interstitium
Urea
• Contributes about 40 to 50% osmolarity of the inner medullary
intersitium

• Urea recirculation provides an additional mechanism for forminh a

hyperosmotic renal medulla

• Urea transporters UT-A1 and UT-A2 in medullary collecting ducts are

activated by ADH
ADH
• Is crucial in maintaining extracellular fluid osmolarity

• Increases water reabsorption in the cortical collecting tubules, so the

high osmolarity of the medullary interstitial fluid is preserved

• Activates urea transporters UT-A1 and UT-A2 in medullary collecting

ducts

• Refers to previous section for more information on ADH

THIRST
• Thirst centers:
• Anteroventral wall of the third ventricle
• Anterolateral part of preoptic nucleus

• Thirst centers work like osmoreceptor cells

Renal Regulation of +
K, 2+
Ca , PO4 -,

and Mg 2+
Potassium
• Normal plasma potassium concentration is about 4,2 mEq/L
• Only 2% of potassium in the human body is in the extracellular fluid
(about 59 mEq)
• Normal meals may contain about 40 mEq of potassium
• As such, potassium must be controlled very precisely.
Renal potassium excretion
• The most important sites for regulating potassium excretion are the
principal cells of the late distal tubules and cortical collecting tubules

• In these segments, potassium can be secreted or reabsorbed,

depending on the needs of the body.
Potassium secretion by principal cells
• Is controlled by:
• Activity of basolateral Na-K-ATPase
• Electrochemical gradient for potassium secretion from the blood to the
tubular lumen
• Permeability of the luminal membrane for potassium
Potassium secretion/reabsorption by
intercalated cells
Regulation of potassium secretion
• Increased extracellular fluid potassium concentration stimulates
potassium secretion
• It stimulates Na-K-ATPase in the basolateral side
• It reduces potassium gradient across extracellular fluid and intercellular fluid,
therefore reducing potassium backleak to the interstitial fluid
• It stimulates synthesis of potassium channels
• It stimulates aldosterone secretion
• Aldosterone secretion increases potassium secretion
• Stimulates basolateral Na-K-ATPase
• Increases the number of potassium channels in the luminal membrane
• Increased distal tubular flow rate stimulates potassium secretion
• Minimize the increase in the tubular potassium concentration
• Increases the number of BK channels in the luminal membrane
• The effect of tubular flow rate on potassium excretion is important in
preserving potassium excretion during changes of potassium intake.

• This effect of tubular flow rate counterbalances the changes in

aldosterone secretion
Calcium
• PTH increases calcium reabsorption in the thick ascending limb and
distal tubules
Phosphate
• The renal tubules have a normal transport maximum for reabsorbing
phosphate of about 0.1 mmol/min. When less than this amount of
phosphate is present in the glomerular filtrate, essentially all the
filtered phosphate is reabsorbed. When more than this amount is
present, the excess is excreted.
• Effects of PTH on phosphate:
• (1) PTH promotes bone resorption, thereby dumping large amounts of
phosphate ions into the extracellular fluid from the bone salts, and
• (2) PTH decreases the transport maximum for phosphate by the renal tubules,
so a greater proportion of the tubular phosphate is lost in the urine.
Magnesium
• The mechanisms that regulate magnesium excretion are not well
understood, but the following disturbances lead to increased
magnesium excretion:
• (1) increased extracellular fluid magnesium concentration
• (2) extracellular volume expansion, and
• (3) increased extracellular fluid calcium concentration.