dcjs: June 2009

1.maintenance of the body fluid
compositions and volumes

2.production of a
low-volume, highly concentrated urine to rid the body of metabolites,
drugs, and other undesirable substances without wasting water
Distribution of Water among the Body Fluids
 body typically contains about 60% water by weight (1 L H2O = 1 Kg)
 intracellular fluid (67% inside cells) and extracellular fluid (33% outside
 cells)
 plasma water (25%) or
 interstitial fluid (75%)
Shifts of Water between Body Fluid Compartments
 Osmotic gradients

 asymmetric distribution of ions across a semi-permeable membrane

 Water will continue to traverse the cell membrane until the
 osmotic pressure on each side of the membrane becomes the same
 (equilibration)
FUNCTIONS:
1. Blood volume and composition
2. Blood pressure
3. Metabolism
PRIMARY FUNCTION…
EXTERNAL ANATOMY
A. Hilus
B. Layers of the Kidney
a. renal capsule
b. adipose capsule
c. renal fascia
NEPHRON
- functional unit of the kidney

3 basic functions:
A. filtration
B. secretion
C. reabsorption

Parts:
A. Renal Corpuscle
B. Renal Tubule
RENAL CORPUSCLE
A. Glomerulus
B. Glomerular (Bowman’s) Capsule

Parts of the renal corpuscle….

The Renal Corpuscle…. Convoluted tubules…

CORTICAL AND JUXTAMEDULLARY NEPHRONS
- Loop of Henle
- Location of Glomerulus
Functions of the Nephrons:
1. Control blood concentration and volume
2. Regulate blood pH
3. remove toxic wastes from the blood

Processes of Urine Formation:
A. Filtration
B. Reabsorption
C. Secretion
GLOMERULAR FILTRATION
- principle is forcing of fluids through a membrane
- occurs in the renal corpuscle
- BP forces water
- resulting fluid is called the FILTRATE
- most proteins are large enough to pass through the endothelial-capsular membrane

 Approximately 25% of the cardiac output or 1200 ml of blood per minute is received by the kidneys.

 One liter of urine is the end product of more than 1000 liters of circulating blood processed through the kidneys.
 The JGA plays a major role in the renin-angiotensin-aldosterone system
 The JGA has also been implicated in the autoregulation of GFR.
renin-angiotensin system
 or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that helps regulate

 long-term blood pressure
 and blood volume in the body.
 The system can be activated when there is a loss of

 blood volume or
 a drop in blood pressure
 decreased perfusion of the juxtaglomerular apparatus in the kidneys then the juxtaglomerular cells release the enzyme renin.

 Renin cleaves an inactive peptide called angiotensinogen, converting it into angiotensin I.

 Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), which is found mainly in lung capillaries
 it is a potent vasoconstrictor.

 In the kidneys, it constricts glomerular arterioles

 increases the arterioler resistance, raising systemic arterial blood pressure

 In the adrenal cortex, it acts to cause the release of aldosterone
 Aldosterone acts on the tubules
 ---reabsorb more sodium and water from the urine.

 acts on the central nervous system to increase a person's appetite for salt, and to make them feel thirsty.
Clinical significance
 The renin-angiotensin system is often manipulated clinically to treat high blood pressure.

 Inhibitors of angiotensin-converting enzyme (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II.

 angiotensin receptor blockers (ARBs) can be used to prevent angiotensin II from acting on angiotensin receptors.

 180 L/day > amount of filtrate that enters the capsular space

 178-179 liters are returned to the bloodstream by reabsorption

 1-2 liters are excreted as urine

Special features of the renal corpuscles enhance their blood filtering capacity:
1. Glomerular capillaries are long
2. The filter (endothelial-capsular membrane) is porous and thin
- fenestrations generally do not restrict
passage of solutes
3. Capillary blood pressure is high
Net Filtration Pressure
Three Main Pressures in the glomerulus:
A. GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP)
- blood pressure inside the glomerular capillaries
- usually 60 mmHg

B. CAPSULAR HYDROSTATIC PRESSURE (CHP)
- due to: a. walls of the capsule
b. fluid that has already filled the renal tubule
- filtrate push back
- 15 mmHg amount of push

C. BLOOD COLLOID OSMOTIC PRESSURE (BCOP)
- due to the presence of PROTEINS
- the greater the solute concentration, the greater is its osmotic
pressure
- usually 27 mmHg
NFP = GBHP - (CHP + BCOP)
Promotes Oppose
Filtration Filtration

Calculation:

GUYTON: GBHP = 60 mmHg
BCOP = 32 mmHg
CHP = 18 mmHg
GLOMERULAR FILTRATION RATE
- the amount of filtrate in all renal corpuscles of both kidneys every minute
- in normal adults ------ 125 ml / min ; 180
L / day
- directly related to NFP
Regulation of GFR
systemic blood pressure and
diameter of afferent and
efferent arterioles
Principal mechanism:
A. Renal Autoregulation of GFR
- operates by negative feedback system
- involves the juxtaglomerular apparatus
B. Hormonal Regulation
Two hormones:
A. Angiotensin II
> Stimuli for renin secretion
1. decreased delivery of fluid and NaCl
to the macula densa
2. decreased stretch of the juxtaglomerular cells
3. sympathetic nerve stimulation

Important action of ANGIOTENSIN II:

1. Vasoconstriction
2. Aldosterone (adrenal cortex)
3. Thirst (hypothalamus)
4. ADH (posterior pituitary gland)
B. Atrial Natriuretic Peptide (ANP)
- secreted by cells in the atria
- stretch of the heart

Important action:
1. promotes excretion of both water and sodium
2. increases GFR > increasing the permeability of
the filter
> dilating the afferent arteriole
3. lowers blood pressure
4. reduces water retention
C. Neural Regulation
- sympathetic stimulation - vasoconstriction
TUBULAR REABSORPTION
1. REABSORPTION IN THE PCT
A. Sodium
- concentration of Na inside tubule cells are low
- interior of the cell is negatively charged
- passive diffusion of Na+ through leakage channels
- Na pumps expel Na through primary active transport
- K+ can diffuse back out through K+ leakage channels
-
MAIN EFFECT: reabsorption of Na+
- active transport of Na+ promotes reabsorption of water through osmosis
- reabsorption of Na+ increases osmotic pressure in the tubule cytosol and in the blood in the peritubular capillaries
B. Nutrients
- 100% of filtered glucose, amino acids and other useful metabolites are reabsorbed in the PCT
- reabsorption by Na+ symporters (secondary active transport)
- Na+ symporter (integral membrane protein)
- substances brought into to the PCT by SYMPORTERS generally leave by facilitated diffusion

Values:
100% - nutrients
80 to 90% - HCO3
65% - Na+ and water
50% - Cl+ and K+
2. REABSORPTION IN THE LOOP OF HENLE
- cells in the thick ascending limb of the Loop of Henle features SYMPORTERS
- simultaneously reclaim one Na+, one K+ and two Cl+ from the filtrate
- secondary active active transport mechanism
- K+ are allowed to recycle through leakage channels
-
MAIN EFFECT: reabsorption of Na+ and Cl+
- DESCENDING LIMB – absorbs water
- ASCENDING LIMB – little or no water

3. REABSORPTION IN THE DCT AND COLLECTING DUCTS
- fine tuning of salt and water reabsorption
- two hormones act on PRINCIPAL CELLS – regulate
absorption

A. Aldosterone
- secreted by adrenal cortex
- increases Na+ and water reabsorption by principal
cells

B. Antidiuretic Hormone (ADH)
- secreted by the post. pituitary gland (hypothalamus)
- increases water permeability by the principal cells
low water concentration in the blood

increased secretion on ADH (osmoreceptors in the hypothalamus

stimulate production of water channels

increased permeability of the apical membranes of principal cells

water is passes into the cells and into the blood

NOTE:
Absent ADH - 20 liters/day of dilute urine
ADH present - 400-500 ml/day of concentrated urine
TUBULAR SECRETION
SECRETION OF H+
- normal blood Ph (7.35 to 7.45)
- occurs in the epithelial cells of the PCT and collecting ducts

Ways in which the cells in the renal tubule can raise the blood pH:
1. secreting hydrogen ions into the filtrate
2. reabsorbing filtered HCO3 (important buffer of H+)
3. producing new HCO3 to augment buffering of H+
CO2
Diffusion from tubular blood
Diffusion from tubular fluid
Metabolic reactions within epithelial cells

presence of carbonic anhydrase (CA)

CO2 combines with water

Forming carbonic acid H2CO3
H2CO3 dissociates into

H+ and HCO3 ions

H+ is secreted into the tubular fluid (filtrate)
accomplished by Na+/H+ antiporters

HCO3 diffuses into the peritubular capillaries
NOTE: for every H+ secreted, one ion of HCO3 is returned to the blood….
secreted H+

combines with filtered HCO3

forming H2CO3

dissociates into CO2 and H2O

CO2 diffuses into the tubule cells

CO2 joins with water forming H2CO3
NOTE: as the H+ is secreted into the tubular fluid, HCO3 is reabsorbed into the blood together with Na+

OVERALL RESULT: reabsorption of Na+ and HCO3
Tubular reabsorption (movement from tubule into interstitial fluid and then blood)
 A) Proximal convoluted tubule -most reabsorption of substances occurs here
 Sodium ions reabsorbed via active symporter pumps.
all glucose and amino acids move with Na in symporter pumps.
 most Cl– and almost all HCO3- ions passively diffuse down their electrical gradient, following Na+
 positive ions (K+ and Ca++) diffuse down their electrical gradient, following negatively charged HC03 and Cl-
 most water moves to accumulation of ions in interstitial fluid (movement of Na+, Cl– and other dissolved substance) by osmosis (osmotic pressure being higher in interstitial fluid than filtrate)
 B). Descending loop of Henle (always permeable to H2O)
 passive H2O reabsorption following osmotic gradient set up by Na and CL reabsorption by ascending loop in medulla (and accumulation of urea also in medulla)
 C. Ascending loop of Henle (always impermeable to H2O)
 does not allow water back into filtrate but pumps out Na and Cl
(Medullary osmotic gradient magnified by this countercurrent multiplier
 D. Distal convoluted tubules
 a) Ca+ reabsorption promoted by PTH.
b) more Cl and Na+ ions reabsorbed promoting little more water reabsorption
 From PCT to DCT all reabsorption is obligatory-it will always occur.

 In the collecting ducts, hormones determine reabsorption.
 E . collecting ducts

 (reabsorption/secretion due to levels of hormone, ADH or Aldosterone)
 water...
a) if high levels of ADH then more water pores made in cells so more water reabsorbed (forming little concentrated urine)
 b) if low levels of ADH then less water pores made in cells so water not reabsorbed (forming copius dilute urine)
 Sodium
 c) if high levels of aldosterone then more Na/K+ pumps made in cells so more Na reabsorption/K secretion
 d) if low levels of aldosterone less Na/K+ pumps made in cells so less Na reabsorption/K secretion.