Renal Blood Flow and Glomerular Filtration

Question 1

What are some of the basic roles of the kidney?

Answer 1

• ridding the body of metabolic by-products, such as urea, creatinine, uric acid.
• excreting toxins and foreign substances
• salt/pH balance
• gluconeogenesis
• conversion of 25-hydroxy vitamin D3 into calcitriol and synthesis of EPO

Question 2

What happens if the kidney fails to function?

Answer 2

there will be edema due to lack of fluid and salt balance.

Increased fluid retention in the body means increased work load to heart. Eventually this leads to heart failure and pulmonary edema.

Question 3

Describe the orientation of nephrons

Answer 3

There are nearly 1 million nephrons in each kidney.
The majority of them are located in the cortex with a part of their tubule extending into outer medulla (aka superficial nephrons), while about 15% of nephrons are in medulla with their glomerulus located in inner part of cortex (aka juxtamedullary nephrons).

Question 4

Distal tubules of 6-8 nephrons join to form ____, which start in the cortex and extend into the medulla.

In the inner medulla, collecting ducts join together to form ____, which open into minor calyx

Answer 4

collecting ducts

ducts of bellini

Question 5

Describe the tubule system of a nephron

Answer 5

• glomerulus
• proximal convoluted tubule from Bowman’s space
• proximal straight tubule (end of proximal tubule)
• thin descending, thin ascending, and thick ascending limbs (LOH)
• distal convoluted tubule
• cortical and medullary collecting ducts
• duct of bellini

Question 6

How much of the CO do the kidneys receive?

Answer 6

20%

Question 7

Describe the initial branching of the renal arteries from the hilum.

Answer 7

Upon entry into the hilus, renal artery divides into several segmental arteries which then divide into several interlobar arteries that radiate from hilus toward the cortex.

Near the boundary between medulla and cortex, the interlobar artery divides into arcuate arteries that run parallel to the arc of the corticomedullary junction

Question 8

Describe the branching from the arcuate arteries.

Answer 8

Arcuate arteries give off radial arteries.

Afferent arterioles branch off from radial arteries, one for every nephron.

Question 9

How do afferent arterioles progress?

Answer 9

Afferent arterioles continues as glomerular capillary beds, that reside inside the Bowman’s space of glomerulus.

Unlike capilary beds in other organs, glomerular capillary beds do not empty into a venule, but into another resistance vessel, the efferent arteriole. The efferent arteriole continues as the second capillary bed, the peritubular capillary bed that surrounds the tubule of nephron

Question 10

Describe the orientation of the peritubular capillary bed.

Answer 10

In the cortex, the peritubular capillaries from the efferent arteriole leaving the glomerulus form a dense plexus surrounding the cortical tubular components (both proximal and distal).

These capillary beds then descend down the ascending limb of the LOH and interact with the tubule system before ascending adjacent to the descending limb as a branch of the renal vein. This part of the capillary bed is called the vasa rectae.

Question 11

T or F. Unlike capillary beds in other organs, in renal vasculature the arteriovenous pressure drop occurs in 2 steps.

Answer 11

T, thus maintaining high hydrostatic pressure in the glomerular capillary to drive filtration*

Question 12

Describe the hydrostatic pressure changes along the renal artery

Answer 12

The pressure in renal artery is about 100 mm Hg. Along the afferent arteriole the pressure drops slowly but only about 60 mm Hg. This pressure is maintained in the glomerular capillary with only a little change.

Question 13

When does pressure drop again?

Answer 13

A second drop in pressure occurs in the efferent arteriole to about 25 mm Hg, which is gradually reduced to about 5 mm Hg in the peritubular capillary where it remains as it returns to the renal vein

Question 14

Why does pressure drop in the afferent, efferent, and the peritubular capillaries?

Answer 14

These 3 segments of vasculature have high resistance to blood flow.

Due to high transmural pressure in these blood vessels they have much thicker smooth muscle rings. The contraction of these muscle cells produce high resistance.

Question 15

Describe the oncotic pressure in the renal system

Answer 15

The oncotic pressure in renal artery and afferent arteriole is about 20 mm Hg.

Along the glomerular capillary the oncotic pressure increases to about 35 mmHg. This is due to glomerular filtration. While the plasma is filtered through glomerular barrier the proteins stay back resulting in gradual increase in protein concentration along the capillary, thus increasing the oncotic pressure. The high oncotic pressure is maintained in the efferent arteriole, but it is gradually reduced in the peritubular capillary due to reabsorption of glomerular filtrate from the proximal tubule.

The high hydrostatic pressure and low oncotic pressure in glomerular capillary help in glomerular filtration.

Question 16

Excretion rate of a solute in the urine is equivalent to what?

Answer 16

GFR - reabsorption + secretion

Question 17

Different substances exhibit different properties in the nephron.

Some substances are freely filtered in glomerulus, but neither reabsorbed by the proximal tubule nor secreted into the tubule; for example _____

Answer 17

inulin (or mannitol)

Question 18

Describe the FAS of sodium and chloride.

Answer 18

freely filtered, partly reabsorbed, but not secreted

Question 19

Describe the FAS of AAs and glucose.

Answer 19

freely filtered and completely reabsorbed in PT

Question 20

Describe the FAS of creatinine.

Answer 20

Freely filtered, not reabsorbed, but secreted by the tubular epithelium in the PT

Question 21

Reabsorption processes require an enormous amount of energy. So, what is the wisdom of filtering a large amounts of body fluids and solutes and reabsorbing most of them back to body?

Answer 21

High GFR allows the kidney to rapidly remove waste products from the body that depend primarily on kidney for their excretion. Most waste products are poorly reabsorbed, therefore, rapid filtration leads to rapid excretion of waste products, otherwise they would be toxic to cells.

Second, high GFR allows body fluids to be filtered and processed several times a day. Total PV is about 3 L and GFR is 180 L/day, so the entire plasma processed 60 times a day. This allows the kidney to precisely and rapidly control the change in body fluid volume and composition.

Question 22

Glomerular filtration is referred to as what?

Answer 22

ultrafiltration, because it allows filtration of all small molecules, but does allow filtration of blood cells and large molecules like proteins.

Therefore, the composition of glomerular filtrate is similar to plasma, except the absence of proteins (and other slight changes).

Question 23

Can monomeric hemoglobin be part of ultra filtrate?

Answer 23

Yes, but this only occurs with hemolysis

Question 24

Describe the composition of other parts of GF.

Answer 24

The levels of some ionic molecules such as Ca2+, phosphates, and fatty acids that bind to proteins are low.

Anion are 4-5% higher then cations in GF. This is due to Gibbs Donnan effect

Question 25

What is a normal GFR?

Answer 25

130ml/min

Question 26

What is filtration fraction?

Answer 26

Filtration fraction is the GFR divided by renal plasma flow (RPF), so it represents the fraction of renal plasma processed by kidney in a given time.

Normal: GFR is 130 ml/min and RPF is 670 ml/min, so 130/670, the FF is 19.4%

Question 27

Factors that reduce GFR reduces FF, for example under conditions of ______.

Answer 27

uretral obstruction.

On the other hand, reduction in RPF increases FF, for example under conditions of renal artery stenosis

Question 28

What is the first barrier the plasma has to penetrate through during the process of glomerular filtration?

Answer 28

The first barrier is the capillary endothelium, consists of a monolayer of flat endothelial cells.

Space between cells is sealed to some extent by junctional complex called tight junction.

Question 29

T or F. The endothelial junctions are leakier than epithelial junctions.

Answer 29

T. Endothelium in kidney is further leakier than endothelium in other organs.

Endothelium of capillaries in other organs does not allow diffusion of plasma proteins. But, the glomerular capillary endothelium allows diffusion of some smaller proteins.

Question 30

What is the second barrier the plasma has to penetrate through during the process of glomerular filtration?

Answer 30

The epithelium (aka podocytes).

The slit pores allow diffusion of small molecules, but does not allow plasma proteins, therefore is the major permeability barrier.

Question 31

What lies between the endothelium and epithelium?

Answer 31

A layer of gel-like substance called the basement membrane.

Question 32

What is the composition of the BM? Function?

Answer 32

This is composed of collagen and proteoglycan fibers.

It is believed to provide some degree of barrier function, but the nature of its barrier function is unclear. It is highly negatively charged, so it can repel negatively charged molecules, such as proteins.

Question 33

What are the filtration criteria?

Answer 33

1. Size selectivity
   Glomerular pores: ~8 nm or 80 angstroms
   Albumin: ~6 nm or 60 angstroms (charge in BM rejects it)
2. Charge selectivity

Question 34

What is the difference between nephritic and nephrotic syndrome?

Answer 34

Both cause proteinuria but:

There could be a visible barrier breakdown and form larger pores which will result in filtration of proteins and cells. An Example is nephritic syndrome.

There could be invisible barrier breakdown due to increased opening of slit pores or loss of charge selectivity. This causes filtration of proteins, but not cells. An example is nephrotic syndrome.

Question 35

What else can cause proteinuria?

Answer 35

Abnormal circulating proteins. For example, breakdown of tissues releasing proteolytically fragmented proteins into the circulation, or there could be production of abnormal proteins, for example proteins produced by tumor cells.

common in diabetics due to decreased BM negative charge

Question 36

What is the eqn for GFR?

Answer 36

GFR is equal to Kf times net filtration pressure.

Question 37

What is Kf?

Answer 37

Kf is the filtration coefficient, which is hydraulic conductivity times the surface area of glomerular capillary.

Question 38

What is hydraulic conductivity? What is it determined by?

Answer 38

Hydraulic conductivity is the ease with the fluid flows through. This is determined by the size and shape of the pores. Normally Kf is 125 ml/min/mm Hg, which is 400 times greater than that in other capillaries.

Any factor that reduces Kf either by reducing hydraulic conductivity or surface area would reduce GFR.

Question 39

How is Kf affected in diabetes mellitus?

Answer 39

In diabetes mellitus GFR is reduced as the Kf is reduced due to increase in basement membrane thickness, so reduced hydraulic conductivity and damaged capillaries, so reduced surface area.

Question 40

What determines net filtration pressure?

Answer 40

The difference between the forces that favor filtration and forces that oppose filtration.

Question 41

What pressures favor filtration?

Answer 41

The glomerular hydrostatic pressure is the major force that favor filtration. The oncotic pressure in the Bowman’s space is another force that favor filtration.

However, there is no such protein present in the fluid in the Bownman’s space, and therefore the Bowman’s space oncotic pressure is almost zero.

Question 42

What is the major force that opposes filtration?

Answer 42

On the other hand the oncotic pressure in the capillary is high due to plasma proteins, This is the major force that oppose filtration.

The other opposing force is the Bowman’s space is hydrostaic pressure caused by fluid accumulation.

Question 43

So, what is the eqn for net filtration pressure?

Answer 43

[Glomerular hydrostatic pressure + Bowmans space oncotic pressure] - [glomerular oncotic pressure and bowman space hydrostatic pressure]

Question 44

The glomerular capillary hydrostatic pressure is about 60 mm Hg of positive filtration pressure. The capillary oncotic pressure is about 31 mm Hg that is a negative filtration pressure, and the Bowman’s space hydrostatic pressure about 20 mm Hg, which is also a negative filtration pressure.

Answer 44

So, 60 (+0) minus 31 minus 20 is 9 mm HG, which is the net filtration pressure. So, GFR may be altered by factors that change any of these forces.

Question 45

Net filtration pressure and therefore GFR can be regulated by changing the glomerular hydrostatic pressure. How can this be accomplished?

Answer 45

This can be changed by changing the resistance of afferent and efferent arterioles.

Question 46

When the resistance in afferent and efferent arterioles are equal the glomerular hydrostatic pressure is about 60 mm Hg. What happens if the resistance of afferent arteriole is increased or resistance of efferent is decreased?

Answer 46

the blood flow into glomerular capillary is reduced and flow out of capillary is increased resulting in reduced glomerular hydrostatic pressure, and therefore reduced GFR.

On the other hand, if the resistance of afferent is reduced or resistance in efferent is increased the glomerular pressure is increased and therefore increased GFR.

So, any neural or hormonal factors that alter the resistance of afferent or efferent arterioles can alter net filtration pressure and therefore GFR.