Driving Force of FiltrationDriving Force of Filtration

The filtration across membranes is driven by the net The filtration across membranes is driven by the net filtration pressurefiltration pressure

The net filtration pressure = The net filtration pressure = net hydrostatic pressure net hydrostatic pressure minus minus the the net colloid osmotic pressurenet colloid osmotic pressure

TheThe net hydrostatic pressure net hydrostatic pressure is determined by the is determined by the glomerular hydrostatic pressure (GHP) glomerular hydrostatic pressure (GHP) minus theminus the capsular capsular hydrostatic pressure (CHP)hydrostatic pressure (CHP)

Hydrostatic PressuresHydrostatic Pressures

TheThe GHP GHP is the blood pressure in the glomerular capillariesis the blood pressure in the glomerular capillaries- tendency to push water and solutes out of plasma, - tendency to push water and solutes out of plasma, across membranesacross membranes- since efferent arteriole is smaller than afferent - since efferent arteriole is smaller than afferent arteriole, GHP is relatively high (50 mm Hg)arteriole, GHP is relatively high (50 mm Hg)

TheThe CHP CHP is the resistance to flow along nephron tubules is the resistance to flow along nephron tubules and ductsand ducts

- tendency to push water and solutes out of filtrate, - tendency to push water and solutes out of filtrate, into into plasmaplasma - CHP is normally low (15 mm Hg)- CHP is normally low (15 mm Hg)

Thus, net hydrostatic pressure = 50 - 15 = 35 mm HgThus, net hydrostatic pressure = 50 - 15 = 35 mm Hg

Colloid Osmotic Pressure (COP)Colloid Osmotic Pressure (COP)

The colloid osmotic pressure is the osmotic pressure The colloid osmotic pressure is the osmotic pressure resulting from the presence of proteins in a solutionresulting from the presence of proteins in a solution

The COP of blood is about 25 mm HgThe COP of blood is about 25 mm Hg The COP of filtrate is normally 0The COP of filtrate is normally 0 Thus, total COP is 25 mm HgThus, total COP is 25 mm Hg

Net Filtration PressureNet Filtration Pressure

Thus, the net filtration pressure = Thus, the net filtration pressure =

net hydrostatic pressure - colloid osmotic pressure net hydrostatic pressure - colloid osmotic pressure

= 35 mm Hg - 25 mm Hg = 10 mm Hg= 35 mm Hg - 25 mm Hg = 10 mm Hg Abnormal changes in either net hydrostatic pressure or Abnormal changes in either net hydrostatic pressure or

colloid osmotic pressure will affect filtration ratecolloid osmotic pressure will affect filtration rate

- damage to glomerulus will allow proteins into the - damage to glomerulus will allow proteins into the filtrate, decreasing net COP, and increasing filtration ratefiltrate, decreasing net COP, and increasing filtration rate

- increasing capsular hydrostatic pressure - increasing capsular hydrostatic pressure (obstruction of tubules, ducts) will markedly decrease net (obstruction of tubules, ducts) will markedly decrease net hydrostatic pressure, decreasing filtration ratehydrostatic pressure, decreasing filtration rate

Regulation of the Urinary System

Endocrine Regulation of Kidney Function

Autoregulation of Kidney Function

Neural (sympathetic) Regulation of Kidney Function

Urine Flow

Endocrine Regulation of Kidney Function

Endocrine Glands: ductless glands which secrete hormones into the circulation, acting at a distant site

Three main hormones are involved in regulation of kidney functions:

- Antidiuretic Hormone (ADH, AVP)

- Aldosterone

- Renin, Angiotensin II

Antidiuretic Hormone

Now called arginine vasopressin (AVP) Synthesized in the brain, released from posterior

pituitary Action: increases permeability of the distal

convoluted tubule and collecting ducts to water Result:

- increased water reabsorption- decreased urine volume- decreased osmolality of interstitial fluids

Antidiuretic Hormone

Regulation of ADH/AVP secretion: Response to osmolality of interstitial fluid:

- Osmoreceptors in the brain detect changes in osmolality

- Increased osmolality results in increased ADH release

- increased water reabsorption

- decreased osmolality of fluids

- Decreased osmolality results in decreased ADH release

- decreased water reabsorption

- increased osmolality of fluids

Antidiuretic Hormone

Regulation of ADH/AVP secretion: Response to changes in blood pressure:

- Blood pressure receptors in heart, aortic arch, and carotid artery

- Increased blood pressure results in decreased ADH

- decreased water reabsorption

- decreased blood volume, blood pressure

- Decreased blood pressure results in increased ADH

- increased water reabsorption

- increased blood volume, pressure

Antidiuretic Hormone

ADH also inhibited by alcohol, caffeine

- decreased water reabsorption

- increased urinary volume

- potential for dehydration Insufficient ADH results in disease: diabetes insipidus

- impaired water reabsorption from DCT, collecting ducts

- increase urine volume 10 times

Aldosterone

Steroid hormone produced in the adrenal cortex Stimulates sodium and chloride uptake from DCT and

collecting duct Increases expression of genes involved in active sodium

transport Since Cl- ions follow Na+ ions, also get increased

resorption of chloride Since Na+ transport out of nephron is linked to K+

transport into nephron, aldosterone increases urinary potassium content

Aldosterone

Thus, decreased aldosterone secretion results in decreased reabsorption of Na+ and Cl-, with increased secretion of K+

- increased osmolarity of urine, loss of sodium

- decreased gradient for water reabsorption in the DCT and collecting tubule (increased water loss)

Regulation of Aldosterone Secretion

Aldosterone is regulated primarily by levels of Na+, K+, and angiotensin II (see next slide)

Decreased [Na+] and increased [K+] in interstitial fluid of adrenal cortex results in increased aldosterone secretion

- increased reabsorption of Na+, secretion of K+ Increased [Na+] and decreased [K+] in interstitial fluid

leads to decreased aldosterone secretion

- decreased reabsorption of Na+, secretion of K+

Renin/Angiotensin System

Blood pressure (and aldosterone secretion) is also regulated by interactions between renin and angiotensin

Renin is produced by the juxtaglomerular apparatus of the kidney

Regulation: renin increases if blood pressure at the afferent arteriole decreases, or if sodium concentrations in the DCT decrease

Action of Renin/Angiotensin System

Action: renin converts angiotensinogen to angiotensin I Angiotensin I is converted to angiotensin II Angiotensin II increases blood pressure

Renin/Angiotensin System

Angiotensin II increases blood pressure two ways:

- Vasoconstriction (decreased diameter of vessels)

- Increased aldosterone release

- aldosterone increases salt reabsorption

- increased osmolality of interstitial fluids

- results in increased ADH secretion, increased water reabsorption

- end result = increased blood pressure

Autoregulation of Kidney Function

If systemic blood pressure (BP) decreases, the afferent arteriole will relax (expand) to allow more blood into the glomerular capillaries

If systemic BP increases, the afferent arteriole can constrict to prevent excessive glomerular pressure

In addition, constriction of the efferent arteriole increases glomerular pressure

Relaxation of the efferent arteriole decreases glomerular pressure

Autoregulation of Kidney Function

Through regulation of afferent and efferent arteriole constriction, the glomerular hydrostatic pressure can be maintained over a wider range of blood pressures

Upper limit: systemic BP of 180. Above this, hydrostatic BP increases, resulting in damage to the kidneys

Sympathetic Regulation of Kidney Function

The kidneys receive neural input from sympathetic fibers Neurotransmitter: norepinephrine Action: constriction of small arteries and afferent arterioles Severe stress or injury causes decreased renal blood supply

and decreased glomerular hydrostatic pressure, resulting in markedly decreased filtration rates and tissue damage

The result of sustained shock: kidney failure

Tubular Load & Tubular Maximum

Tubular Load: the total amount of a substance that passes through the filtration membrane per minute

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

Example: tubular maximum of glucose is 320 mg/min

In diabetics, this maximum is exceeded, resulting in glucose in the urine.

Urine Flow: Kidneys to Bladder

Flow from the kidney to the bladder requires peristaltic contraction of the ureters

- hydrostatic pressure at renal pelvis = 0

- contractions increased by parasympathetic innervation

- contractions occur every few seconds to minutes

Urine Flow: Micturition

Micturition: release of urine from the bladder Mechanism: micturition reflex

- stretch receptors in bladder wall cause parasympathetic firing

- bladder wall contracts

- internal urinary sphincter relaxes (smooth muscle)

- external sphincter required to control timing of micturition