Glomerular Filtration and Regulation

Glomerular filtration

the process by which plasma water and solutes move from glomerular capillaries into Bowman’s space

What is the first step in urine formation?

glomerular filtration of water/solutes into Bowman’s space

What is the purpose of filtration?

allows removal of metabolic waste

enables regulation of water, electrolytes, and acid-base balance

provides the starting material for tubular processing

The ____ ensures efficient yet selective filtration of the plasma.

glomerular filtration barrier

Glomerular filtration rate depends on ____ and is tightly regulated.

Starling forces

Measurement of GFR provides critical insight into _____.

how well the kidney filters blood

GFR directly assesses filtration ____, not just urine production.

capacity

GFR can be estimated by _____.

Creatinine (Cr) clearance

What is the formula for clearance?

plasma concentration X amount excreted per minute

urine Cr mg/dL X urine (mL/min)/ plasma Cr

Filtration Fraction (FF)

the fraction of renal plasma flow that is filtered across the glomeruli into Bowman’s capsule

What is the normal filtration fraction value?

0.20 or 20%

About ___ of plasma entering the kidneys is filtered, while ___ leaves via the efferent arteriole.

20%

80%

What is the physiological significance of the glomerular filtration fraction?

1. Indicates the balance between renal blood flow and filtration

2. Helps assess changes in glomerular hemodynamics

3. Affects peritubular capillary reabsorption (an increase, increases oncotic pressure)

Glomerular filtration rate (GFR)

the volume of plasma filtered per unit time by all functioning glomeruli; reflects overall kidney function

Glomerular Capillary Hydrostatic Pressure (PGC)

main driving force for filtration

Bowman’s Space Hydrostatic Pressure (PBS)

opposes filtration and increases with urinary obstruction

Glomerular Capillary Oncotic Pressure (πGC)

pulls fluid back into capillaries

it increases along the capillary as fluid is filtered

Net Filtration pressure (NFP)

PGC - (PBS + πGC)

a positive value is required for filtration to occur

Where is the glomerulus located?

between the afferent arteriole (incoming blood) and the efferent arteriole (outgoing blood) and is surrounded by Bowman’s capsule

What does the glomerular filtration barrier consist of?

1. fenestrated capillary endothelium

2. glomerular basement membrane (GBM)

3. Podocytes and slit diaphragms

What is the significance of fenestrated capillary endothelium?

It has large pores and is freely permeable to water and small molecules

prevents the passage of blood cells

What is the significance of the glomerular basement membrane (GBM)?

It is a thick, negatively charged matrix that repels proteins

Restricts large and negatively charged proteins (e.g. albumin)

What is the significance of podocytes and slit diaphragms?

Podocytes are specialized epithelial cells with slit pores that provide size selectivity

____ and ____ ensure that plasma proteins remain in the blood.

Size

Charge selectivity

What is an additional part of the glomerular filtration barrier that contributes to rapid and efficient filtration?

a large filtration surface area

What is the purpose and normal value for hydrostatic pressure in glomerular capillaries (P_GC)?

a force favoring filtration

45 mmHg

What is the purpose and normal value of hydrostatic pressure in Bowman’s space (P_BS)?

a force opposing filtration

10 mmHg

What is the purpose and normal value of oncotic pressure in glomerular capillaries (π_GC)?

a force opposing filtration

19 mmHg

Net filtration is the pressure ____ minus the sum of pressures ____.

favoring

opposing

What does constriction of the afferent arteriole do?

causes a decrease of P_GC, which decreases filtration of the glomerulus (GFR)

What does constriction of the efferent arteriole do?

causes an increase in P_GC, which increases filtration of the glomerulus (GFR)

Changes in plasma protein concentration produces changes in which pressure?

glomerular capillaries oncotic pressure (π_GC)

Increases in plasma protein concentration (e.g. dehydration) will ___ π_GC which ____ filtration, ultimately ___ GFR.

increase

opposes

decreasing

Decreases in plasma protein concentration (e.g. nephrotic syndrome) will ___ π_GC which ____ filtration, ultimately ___ GFR.

decrease

opposes

increasing

Nephrotic syndrome

condition in which large amounts of protein are lost in the urine

What does intrinsic regulation (renal autoregulation) of GFR consist of?

Myogenic mechanism

Tubuloglomerular feedback

The myogenic mechanism involves ______ in response to stretch from increased blood pressure, which protects the glomerulus and ____ GFR regardless of Pa fluctuations.

constriction of the afferent arteriole smooth muscle

stabilizes

What is tubuloglomerular feedback?

The macula densa of the distal tubule senses NaCl concentration in the filtrate and regulates afferent arteriole tone

Which arteriole is affected by tubuloglomerular feedback?

the afferent arteriole

High NaCl results in afferent arteriole ____ and ____ GFR.

constriction

decreased

Low NaCl results in afferent arteriole ___ and ____ GFR.

dilation

increased

What are the components of the juxtaglomerular apparatus (JGA)?

1. Macula densa

2. Juxtaglomerular (JG) cells

3. Extraglomerular Mesangial cells

The macula densa senses tubular ____ concentration and regulates ___ arteriole tone.

NaCl

afferent

The macula densa stimulates ___ release from the juxtaglomerular cells.

renin

Juxtaglomerular (JG) cells

modified smooth muscle cells of afferent and efferent arterioles that secrete renin when stimulated appropriately

Juxtaglomerular (JG) cells secrete renin when stimulated by ___ P_a, sympathetic NS, and PGE₂ from the macula densa.

decreased

What do extraglomerular mesangial cells do?

signal transmission between the macula densa and JG cells, while also providing structural support to the juxtaglomerular apparatus

Increase in renal blood flow (RBF) ____ GFR and leads to ___ Na+ filtration.

increases/increased

Adenosine

released by the macula densa cells and constricts the afferent arteriole

If NaCl levels in the filtrate are ___, macula densa cells release adenosine, which acts on afferent and efferent arterioles.

high

When adenosine binds to A₁ adenosine receptors, this results in _____.

constriction of the afferent arteriole

When adenosine binds to A₂ adenosine receptors, this results in ____.

dilation of the efferent arteriole

How does the Renin—Angiotensin—Aldosterone System (RAAS) work?

It is activated by low blood pressure or low NaCl, renin is secreted, and angiotensin II is formed

What does Angiotensin II do?

it constricts the efferent arteriole and helps maintain GFR during hypovolemia

Atrial natriuretic peptide (ANP)

a hormone that increases glomerular filtration rate when there is an increase in blood volume

Antidiuretic hormone (ADH)

a hormone that indirectly influences GFR by increasing water retention, which expands blood volume, raises blood pressure, and thereby helps maintain or increase glomerular filtration

What is another common name for ADH?

VasopressinThe

The sympathetic nervous system causes peripheral ___ of arterioles during emergency situations, including the afferent arteriole of the kidney.

constriction

The sympathetic nervous system ___ GFR during stress, severe blood loss, or shock.

decreases

Angiotensin II stimulates the ___ to secrete aldosterone.

adrenal cortex

Aldosterone

hormone that acts on the renal tubules to increase sodium reabsorption and an increase in ECF

ADH acts on the renal collecting ducts to ____ water reabsorption, which leads to an ___ in blood volume

increase/increase

In response to increased blood volume and stretch of receptors, the opposite atria secretes ___ and sends a signal to the ____.

ANP

hypothalamus

ANP ____ GFR, ____ Na+ reabsorption, and ___ the excretion of sodium and urine.

increases/decreases/increases

When the hypothalamus decreases the secretion of ADH, the result is ___ blood volume and P_a.

decreased

SDMA (Symmetric Dimethylarginine)

a substance that is produced by the muscle metabolism of proteins and serves as a marker of GFR

SDMA is ___ sensitive than creatinine and ___ affected by muscle mass than creatinine.

more

less

Substances left in the tubular fluid in the collecting ducts will be ____.

excreted as urine