Renal Physiology

What are some examples of metabolic waste products?

Urea, creatinine, bilirubin, hydrogen

What are some examples of foreign chemicals?

Drugs, toxins, pesticides,, food additives

What is gluconeogenesis?

Glucose synthesis from amino acids

What structure does blood enter the kidney through?

The afferent arteriole

When the afferent arteriole is constricted what happens to GFR?

It decreases GFR

What is the function of the glomerular capillary?

To filter blood

What is the function of the efferent arteriole?

To drain blood from the glomerulus

What happens within the peritubular capillaries?

Gas exchange

What is the function of the Glomerular (Bowmans) capsule?

Collects filtrate & channels it into the renal tubule

What is the function of the PCT?

Reabsorption & Secretion

What kinds of substances does the PCT reabsorb?

Na+, H20, nearly all glucose/amino acids, bicarbonate, K+, and other ions

What kinds of substances does the PCT secrete?

Hydrogen ions, ammonia, and organic substances

What is the function of the nephron loop?

Establishes the medullary concentration gradient for H20 reabsorption

What is the descending loop of the nephron loop permeable to? Inpermeable to?

H20, Na+

What is the ascending loop permeable to? Impermeable to?

Na+, H20

What is the function of the DCT?

Fine-tunes reabsorption and secretion under hormonal control

What does the DCT secrete?

H+ ions and K+

What does the DCT reabsorb? Via what hormone or gland?

Na+ & Cl- via aldosterone

Ca2+ via parathyroid gland

What is the function of the CD?

Makes the final adjustment of urine composition and concentration

The cortical nephrons have a _____ loop

Short

Which nephron loop makes up 85% of nephrons?

Cortical

Which nephron loop generates the concentration gradient in medulla for H20 reabsorption?

Juxtamedullary

Which nephron loop functions to filter blood?

Cortical

The juxtamedullary nephron is located in the…

Medulla, in the vasa recta

The cortical nephron loop is located in the…

Cortex, in the peritubular capillaries

What are the 3 basic steps of urine formation in the nephron?

1. Glomerular Filtration

2. Tubular Secretion

3. Tubular Reabsorption

Is reabsorption and secretion regulated in the PCT? If so, by what?

No

Is reabsorption and secretion regulated in the DCT? If so, by what?

Yes, by hormones

What is the resulting component of glomerular filtrate?

Plasma but no proteins - blood cells & proteins stay in the blood

What are the components of the filtration membrane?

• Epithelium

• Basement Membrane

• Endothelium

What does the epithelium contain?

Podocytes

What is the function of the basement membrane?

Repels proteins & is negatively charged

What makes up the endothelium?

The glomerular capillary

What is a normal GFR?

125ml/min

How would you calculate Net Filtration Pressure?

Glomerular Hydrostatic Pressure - Bowmans Capsule Pressure - Glomerular Oncotic Pressure

What is net filtration pressure modulated by?

Vasoconstriction/dilation of the afferent and efferent arteriole

What occurs if GFR is too low?

Wastes accumulate

What occurs if GFR is too high?

You lose an increased amount of H20 and electrolytes

Can the afferent and efferent arteriole regulate filtration?

No; but they can regulate GFR

What is renal auto regulation/intrinsic control?

Ability of nephrons to adjust blood flow in order to maintain GFR despite changes in BP

What are some of the auto-regulation mechanisms…

• Myogenic mechanism

• Macula densa feedback

• Tubuloglomerular feedback

What occurs during the myogenic mechanism?

Smooth muscle automatically contract when stretched so…

If BP increases = the stretch of the afferent arteriole increases = vasoconstriction increases = Pgc decreases = GFR decreases → this maintains GFR despite the increase in BP

How do the macula densa cells regulate GFR?

They monitor how much filtrate is formed

What occurs during tuboglomerular feedback to regulate GFR?

Increase in BP (high GFR) = rapid flow of filtrate in renal tubules = macula densa in the DCT sense this = paracrine secretion of adenosine occurs = afferent arteriole constricts = decreased Pgc = reduced GFR

How does Ang II play a role in regulating GFR?

Macula densa sense a low BP/low GFR = stimulates SNS to secrete renin = increased release of Ang II = vasoconstricts the efferent arteriole & increases BP

Where is Na+ reabsorbed mainly?

The PCT

What are the mechanisms by which Na+ is reabsorbed?

• Active transport via Na+/K+ ATPase pump

• Co-transport with other solutes (glucose, amino acids) in PCT

• Passive diffusion in CD regulated by aldosterone

Where is Cl- reabsorbed?

PCT

What is the mechanism in which Cl- is transported?

Active transport

Where is K+ mainly reabsorbed?

PCT

What is the mechanism by which K+ is reabsorbed?

Active transport

Where is H20 mainly reabsorbed?

PCT

What is the mechanism by which H20 is reabsorbed?

Osmosis via aquaporins

Where is glucose reabsorbed?

Fully in PCT (if healthy individual)

What is the mechanism in which glucose is reabsorbed?

Na+ coupled co-transport

Where is urea reabsorbed?

PCT

What is the mechanism in what urea is reabsorbed?

Passive diffusion & transporters

What is the role of tubular secretion?

To move substances from the blood into the tubule

Where is K+ secreted?

DCT & CD

Which hormone/mechanism secretes K+?

Aldosterone; via active transport via Na+/K+ ATPase pump

Where are H+ ions secreted?

DCT

What is the mechanism for secretion?

Active transport, typically coupled to Na+

Where is urea secreted?

Loop of henle

What is the mechanism of secretion of urea?

Passive diffusion

Where are drugs and toxins secreted?

PCT

What is the mechanism for secretion of drugs and toxins?

Active transport

What is a transport maximum?

Maximum rate at which a substance can be reabsorbed or secreted by renal tubules & occurs when all transport proteins are fully saturated

What happens when there is a transport maximum?

Some solute wont be reabsorbed and will appear in urine → only occurs in a diseased state

If a patient has hyperglycemia (diabetes mellitus) will a transport maximum occur?

Yes; glucose will appear in urine due to all transporters being occupied. This is why patients with diabetes often have glycosuria

Why is urine regulated?

So the fluid output matches the fluid input

Where is most Na+ reabsorbed? Is it regulated there? If so, by what?

PCT, not regulated

Where is Na+ regulated? By what?

The distal nephron

Aldosterone builds Na+ channels and Na+/K+ pumps

ANP inhibits Na+ channel activity

What is the role of the countercurrent multiplier in urine formation?

• Creates medullary osmotic gradient

• H20 reabsorption

• Fine-tunes urine concentration via ADH

What is the function of aldosterone?

Increases Na+ reabsorption & K+ secretion to regulate blood pressure

Indirectly retains water via Na+ retention

What is aldosterone’s mechanism of action?

Binds to intracellular receptors in cells of target site, increasing the expression of Na+/K+ ATPase pumps and channels

Where does aldosterone work?

DCT & CD

What are the effects of aldosterone?

An increase in BP & BV

What is the function of ANP?

Reduces Na+ reabsorption & water retention to decrease BP & BV

What is the mechanism of action of ANP?

Inhibits Na+ channels, and suppresses renin and aldosterone secretion

Relaxes afferent arterioles which increases GFR which increases Na+ excretion

Where does ANP work?

CD & DCT

What are the effects of ANP?

Increased urine production, decreased Na+ reabsorption, increased Na+ excretion which decreases BP & BV

What is the function of ADH?

Regulates H20 balance by increasing H20 reabsorption, decreasing urine volume, and maintaining BP

What is the mechanism of action of ADH?

Binds to V2 receptors on collecting duct cells

Stimulates insertion of aquaporin-2 H20 channels

Where does ADH work?

CD

What are the effects of ADH?

Increases H20 reabsorption, concentrates urine and urine volume

Indirectly supports Na+ reabsorption by maintaining gradient in medulla

When BP or BV is low, what hormones would be active?

Aldosterone and ADH to promote Na+ and H20 retention to restore volume and pressure

When BP or BV is high what hormone would be active?

ANP - because it counteracts aldosterone and ADH, by promoting Na+ and H20 excretion to reduce volume and pressure

What is ANP released in response to?

High blood volume or atrial stretch

What is ADH release in response to?

High plasma osmolarity, or low blood pressure

What stimulates the release of aldosterone?

Low blood pressure

Where are osmoreceptors found?

Hypothalamus

Where are volume receptors found?

Atria of the heart

What stimulates osmoreceptors?

Changes in osmolarity (solute concentration) of body fluids

What stimulates volume receptors?

Changes in blood volume and pressure

How do osmoreceptors work?

They detect changes in osmolarity by cell shrinkage, or swelling

How do volume receptors work?

Detect mechanical stretch in the walls of the atria or veins

How do osmoreceptors respond to a high osmolarity?

ADH is released to promote H20 reabsorption

Triggers thirst to increase H20 intake

How do volume receptors respond to a low blood volume?

It reduces stretch, which stimulates ADH & activates the RAAS

How do volume receptors respond to a high blood volume?

ANP release is stimulated promoting natriuresis and diuresis